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The hydrodynamic (gel filtration and sedimentation) properties of an isolated monoclonal IgM-K cryoglobulin (McE.) and five non-cryoglobulin cold-soluble proteins, as well as their constituent monomeric subunits and (Fc)5mu and Fabmu fragments, are compared under both native and partially denaturing conditions. It is concluded that the cryoimmunoglobulin exhibits a significantly greater Stokes radius than the non-cryoglobulin reference proteins, and that this difference arises in the Fabmu region of the McE. molecule. When the proteins and their fragments are analysed by circular dichroism in the far u.v. region, an atypical conformation is again detected in the Fabmu region of the cryoglobulin. These findings are the first demonstration and partial structural localization of a conformation anomaly in a monoclonal cryoimmunoglobulin. | Cryoglobulins |
Cysteine dioxygenase (CDO) catalyzes the oxidation of l-cysteine to cysteine sulfinic acid. Deficiencies in this enzyme have been linked to autoimmune diseases and neurological disorders. The x-ray crystal structure of CDO from Mus musculus was solved to a nominal resolution of 1.75 Angstroms. The sequence is 91% identical to that of a human homolog. The structure reveals that CDO adopts the typical beta-barrel fold of the cupin superfamily. The NE2 atoms of His-86, -88, and -140 provide the metal binding site. The structure further revealed a covalent linkage between the side chains of Cys-93 and Tyr-157, the cysteine of which is conserved only in eukaryotic proteins. Metal analysis showed that the recombinant enzyme contained a mixture of iron, nickel, and zinc, with increased iron content associated with increased catalytic activity. Details of the predicted active site are used to present and discuss a plausible mechanism of action for the enzyme. | Cysteine Dioxygenase |
Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by a high incidence of skin cancers. Yeast RAD30 encodes a DNA polymerase involved in the error-free bypass of ultraviolet (UV) damage. Here it is shown that XP variant (XP-V) cell lines harbor nonsense or frameshift mutations in hRAD30, the human counterpart of yeast RAD30. Of the eight mutations identified, seven would result in a severely truncated hRad30 protein. These results indicate that defects in hRAD30 cause XP-V, and they suggest that error-free replication of UV lesions by hRad30 plays an important role in minimizing the incidence of sunlight-induced skin cancers. | DNA Polymerase iota |
Cleidocranial dysplasia is an autosomal-dominant condition characterised by widely patent calvarial sutures, clavicular hypoplasia, supernumerary teeth and short stature. Though it is not a very uncommon occurrence, its histopathological features are not frequently reported. This paper presents a similar case with complete clinical, radiological, histological and treatment profiles. | Cleidocranial Dysplasia |
The decreasing availability of energy and concern about climate change necessitate the development of novel sustainable energy sources. Fusion energy is such a source. Although it will take several decades to develop it into routinely operated power sources, the ultimate potential of fusion energy is very high and badly needed. A major step forward in the development of fusion energy is the decision to construct the experimental test reactor ITER. ITER will stimulate research in many areas of science. This article serves as an introduction to some of those areas. In particular, we discuss research opportunities in the context of plasma-surface interactions. The fusion plasma, with a typical temperature of 10 keV, has to be brought into contact with a physical wall in order to remove the helium produced and drain the excess energy in the fusion plasma. The fusion plasma is far too hot to be brought into direct contact with a physical wall. It would degrade the wall and the debris from the wall would extinguish the plasma. Therefore, schemes are developed to cool down the plasma locally before it impacts on a physical surface. The resulting plasma-surface interaction in ITER is facing several challenges including surface erosion, material redeposition and tritium retention. In this article we introduce how the plasma-surface interaction relevant for ITER can be studied in small scale experiments. The various requirements for such experiments are introduced and examples of present and future experiments will be given. The emphasis in this article will be on the experimental studies of plasma-surface interactions. | Tritium |
Polyglutamine expansion in the protein ATAXIN-1 (ATXN1) causes spinocerebellar ataxia type 1 (SCA1), an inherited neurodegenerative disease characterized by motor deficits, cognitive impairment and depression. Although ubiquitously expressed, mutant ATXN1 causes neurodegeneration primarily in the cerebellum, which is responsible for the observed motor deficits. The role of ATXN1 outside of the cerebellum and the causes of cognitive deficits and depression in SCA1 are less understood. In this study, we demonstrate a novel role of ATXN1 in the hippocampus as a regulator of adult neurogenesis. Adult hippocampal neurogenesis is the process of generating new hippocampal neurons and is linked to cognition and mood. We found that loss of ATXN1 causes a decrease in hippocampal neurogenesis in ATXN1 null (Atxn1(-/-)) mice. This decrease was caused by reduced proliferation of neural precursors in the hippocampus of Atxn1(-/-) mice, and persisted even when Atxn1(-/-) hippocampal neural precursors were removed from their natural environment and grown in vitro, suggesting that ATXN1 affects proliferation in a cell-autonomous manner. Moreover, expression of ATXN1 with a pathological polyglutamine (polyQ) expansion in wild-type neural precursor cells inhibited their proliferation. Our data establish a novel role for ATXN1 in the hippocampus as an intrinsic regulator of precursor cell proliferation, and suggest a mechanism by which polyQ expansion and loss of ATXN1 affect hippocampal function, potentially contributing to cognitive deficits and depression. These results indicate that while depletion of ATXN1 is a promising therapeutic approach to treat the cerebellar aspects of SCA1, this approach should be employed with caution given the potential for side effects on hippocampal function with loss of wild-type ATXN1. | Ataxins |
The lead and cadmium contents of 50 species and 19 condiments were investigated by means of flameless atomic absorption spectrophotometry. Mercury contents were determined by cold vapor atomic absorption method including amalgamation. The mean concentrations of lead, cadmium, and mercury were 0.470 mg/kg, 0.080 mg/kg, and 0.005 mg/kg, respectively. By using the detected levels of these three heavy metals in model calculations only a small carry-over of lead, cadmium, and mercury in meat products by species and condiments can be assumed. | Condiments |
Burnup calculations are applied to determine the amount of krypton-85 that is produced during the irradiation of nuclear fuel. Since krypton-85 is most likely released into the atmosphere during reprocessing to separate plutonium, atmospheric transport modeling is used to calculate the worldwide distribution of krypton-85 concentrations stemming from emissions from declared reprocessing plants. The results are the basis for scenarios in which emissions from clandestine reprocessing facilities have to be detected against various background levels. It is concluded that today's background imposes heavily on the ability to detect small and medium plutonium separation rates; only high separation rates of 1 SQ per week and higher have a chance to be detected with feasible outlay. A fixed network of monitoring stations seems too costly; instead the high number of samples that are required rather calls for mobile sampling procedures, where air samples are collected at random locations over the world and are analyzed in regional laboratories for their krypton-85 concentration. Further, it is argued that krypton-85 emissions from declared reprocessing activities have to be significantly lowered to enable a worldwide verification of the absence of even smaller clandestine reprocessing. For each scenario the number of samples that have to be taken for probable detection is calculated. | Krypton Radioisotopes |
AIM: Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS. METHODS: A total of 29 BS patients and 15 healthy controls were enrolled. Real-Time PCR was used to detect the mRNA expression levels of IFN-gamma, CXCR3, CXCL9 and CXCL10 in peripheral blood mononuclear cells (PBMCs) of BS patients and healthy controls. Hematoxylin-Eosin staining was used to show the pathological changes in BS lesion tissues. Immunohistochemistry staining was used to show the protein expression levels of Brucella-Ab, IFN-gamma, CXCR3, CXCL9 and CXCL10 in BS lesion tissues. At the same time, ELISA was used to detect the serum levels of IFN-gamma, CXCL9 CXCL10 and autoantibodies against CXCR3 in patients with BS. RESULTS: In lesion tissue of BS patients, it showed necrosis of cartilage, acute or chronic inflammatory infiltration. Brucella-Ab protein was abundantly expressed in close lesion tissue. And the protein expression levels of IFN-gamma, CXCR3 and CXCL10 were highly expressed in close lesion tissue and serum of BS patients. At the same time, the mRNA expression levels of IFN-gamma, CXCR3 and CXCL10 in PBMCs of BS patients were significantly higher than those in controls. CONCLUSION: In our research, the expression levels of IFN-gamma, CXCR3 and its ligands were significantly higher than those in controls. It suggested that high expression levels of IFN-gamma, CXCR3 and its ligands indicated a serious inflammatory damage in patients with BS. | Receptors, CXCR3 |
BACKGROUND AND OBJECTIVE: It has been demonstrated that smoking significantly reduces postoperative nausea and vomiting (PONV). However, there are approximately 4000 substances in cigarette smoke that can be responsible for this effect. To demonstrate whether nicotine is the substance with antiemetic effects we applied a nicotine patch in patients undergoing laparoscopic cholecystectomy under general anaesthesia. METHODS: Seventy-five patients classified as ASA (American Society of Anesthesiologists' classification) I/II were divided in three groups: group 1 (n = 25), which comprised non-smokers; group 2 (n = 25), which comprised patients who had given up smoking for the last 5 years and received perioperatively a nicotine patch that contained 16.6mg nicotine/patch; and group 3 (n = 25), which comprised actual smokers. Postoperatively, the incidence of PONV and the need for antiemetic rescue medication were monitored every 6 hours. RESULTS: We found a significant reduction in the incidence of PONV in group 2 (5/25 [20%], p = 0.0001 vs group 1) and group 3 (8/25 [32%], p = 0.002 vs group 1) compared with group 1 (18/25 [76%]). The difference in incidence of PONV between group 2 and group 3 was not significant (p > 0.05). CONCLUSIONS: Nicotine significantly reduced the incidence of PONV after laparoscopic cholecystectomy. | Antiemetics |
Parkinsonism is a clinical syndrome, which is characterized by bradykinesia, rigidity, rest tremor, and postural instability. Idiopathic Parkinson disease (PD) is the most common cause of this syndrome, though there are several other important etiologies that must be considered. These include the atypical Parkinsonian disorders multiple system atrophy (MSA), dementia with Lewy Bodies (DLB), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS); as well as secondary causes of parkinsonism. These various disease entities may be distinguished based on key clinical features, which is critical for the purposes of diagnosis, treatment, and prognosis. | Basal Ganglia Diseases |
1. Ascorbate oxidase has been isolated from the green squash Cucurbita pepo medullosa by a new purification method. Furthermore a low-molecular-weight copper protein containing one type-1 copper/20000 Mr could be separated during the purification of the oxidase. The six-step procedure developed improved the yield of ascorbate oxidase by a factor of 2.5. The method is well reproducible and a constant value of 8 Cu (7.95 +/- 0.1/140000 Mr) has been established. By ultracentrifugal and electrophoretic criteria the enzyme preparations have been found to be homogeneous. They exhibited a specific activity of 3930 +/- 50 units/mg protein or 1088 +/- 15 units/microgram copper. 2. The pure enzyme is characterized by the following optical purity indices: A280/A610 = 25 +/- 0.5, A330/A610 = 0.65 +/- 0.05 and A610/A500 = 7.0 +/- 0.25. The molar absorption coeffient of the characteristic absorption maximum at 610 nm (oxidized minus reduced) amounts of 9700 M-1 cm-1 . 3. Computer simulations of the electron paramagnetic resonance (EPR) spectra of the oxidized enzyme reveal the following parameters: for the type-1 (blue) copper gz = 2.227, gy = 2.058, gx = 2.036; Az = 5.0 mT, Ay = Ax = 0.5 mT, for the type-2 (non-blue) copper g parallel to = 2.242, g perpendicular = 2.053; A parallel to = 19.0 mT, A perpendicular 0.5 mT. Out of the eight copper atoms present in the oxidase four are detectable by EPR. Of these, three belong to the type-1 class, and one to the type-2 class, as demonstrated by computer simulations of the EPR spectra. 4. To achieve full reduction of the enzyme, as measured by bleaching of the blue chromophore, four equivalents of L-ascorbate or reductase must be added in the absence of molecular oxygen. Upon reduction of the enzyme the fluorescence at 330 nm (lambda max ex = 295 nm) is enhanced by a factor of 1.5 to 1.75. The reduced enzyme is readily reoxidized by dioxygen, ferricyanide or hydrogen peroxide. It binds two molecules of hydrogen peroxide in the oxidized state (1/type-3 Cu pair), which can be monitored by a characteristic increase of the absorbance around 310 nm (delta epsilon = 1000 +/- 50 M-1 cm-1). Corresponding changes in EPR and fluorescence spectra have not been detected. | Ascorbate Oxidase |
On studying the state of the art in Plastic and Reconstructive Surgery there are two different aspects that have achieved very different levels of advance and progress: the organisation and establishment of this speciality, and scientific and technical progress. In an analysis of the former. The author outlines the principal problems facing Plastic Surgery in Portugal, the present shortcomings and the almost complete lack of coherent planning, and the prevailing rules for the training of new specialists. A study of the second aspect reveals manifest progress and innovation in many areas of this speciality. The Author describes in greater detail, controlled tissue growth, innovations with flaps, principally facial-cutaneous and inverted flow, advances in the remodelling of the face where there are many examples of implantation of material, modelling osteotomy and surgical interventions in the field of muscular dynamics, and lipo-aspiration which has extended horizons in both Plastic and Reconstructive Surgery. | Specialties, Surgical |
Lactococcus lactis degrades exogenous proteins such as beta-casein to peptides of 4-30 amino acids, and uses these as nitrogen sources. The binding protein or receptor (OppA(Ll)) of the oligopeptide transport system (Opp) of L.LACTIS: has the unique capacity to bind peptides from five up to at least 20 residues. To study the binding mechanism of OppA(Ll), nonameric peptides were used in which the cysteine at position 1, 3, 4, 5, 6, 7 or 9 was selectively labeled with either bulky and non-fluorescent or bulky and fluorescent groups. Also, nonameric peptides with a non-natural residue, azatryptophan, at positions 3 or 7 were used. The fluorescence of azatryptophan reports on the polarity of the environment. The studies indicate that the binding protein encloses the first six amino acids of the peptide, whereas the remaining residues stick out and interact with the surface of the binding protein. The peptide binding mechanism of OppA(Ll) is discussed in relation to known three-dimensional structures of members of this class of proteins, and an adaptation of the general binding mechanism is proposed." | 4-Chloromercuribenzenesulfonate |
The purpose of the study was to examine relationships between sleep insufficiency, depressive symptoms, demographic factors, and the nonmedical use of prescription medications (NMUPMs) in the U.S. high school students. Data from the 2013 Youth Risk Behavioral Surveillance System were used ( n = 13,570) and analyzed using IBM SPSS 23 (complex samples). Significant bivariate relationships were found between the NMUPMs and sleep ( p < .01), feeling sad ( p < .001), grade level ( p < .001), and race/ethnicity ( p < .01). Logistic regression analyses found that all of the independent variables were significant in predicting the likelihood of the NMUPMs. Findings underscore the potential impact of preventing NMUPMs in high school adolescents by improving their sleep behaviors and assessing adolescents for depressive symptoms. | Prescription Drug Misuse |
The purpose of this study was to follow the progression of gross and histologic lesions and apoptosis events in Lawsonia intracellularis-infected enterocytes through the course of the disease, proliferative enteropathy (PE). Thirty 5-week-old pigs were divided into 2 groups: 20 challenged and 10 control animals. Groups of 3 pigs, 2 challenged and 1 control, were euthanized at 1, 3, 5, 8, 11, 15, 19, 24, 29, and 35 days after inoculation. Complete necropsies were performed with gross evaluation. Tissue samples from different sites of the gastrointestinal tract and other visceral organs were collected for routine histologic staining and for immunohistochemistry (IHC) for L. intracellularis. In addition, caspase-3, terminal deoxyuridine nick-end labeling assay, and electron microscopy were performed in ileum samples. Macroscopic and histologic lesions suggestive of PE were first detected 11 days after infection and continued through day 24. L. intracellularis antigen was first detected in the intestine by IHC on day 5 after inoculation, and the bacterium was first detected by transmission electron microscopy on day 15. Positive IHC staining for [L. intracellularis] and enterocyte proliferation, but no gross lesion, were detected on day 29. All 3 pigs euthanized on day 35 were grossly and histologically normal and IHC negative. Hyperplastic crypts in challenge pigs had more apoptotic cells on days 15, 19, and 24 postinfection ( P < .05) compared to control pigs. Our results demonstrated the progression of lesions and infection by L. intracellularis and that inhibition of enterocyte apoptosis is not involved in the pathogenesis of proliferative enteropathy." | Desulfovibrionaceae Infections |
We describe a novel, semiautomated Clostridium difficile typing platform that is based on PCR-ribotyping in conjunction with a semiautomated molecular typing system. The platform is reproducible with minimal intra- or interassay variability. This method exhibited a discriminatory index of 0.954 and is therefore comparable to more arduous typing systems, such as pulsed-field gel electrophoresis. | Bacterial Typing Techniques |
Protease activity was studied in the frog sciatic nerve. The activity was measured as the release of TCA-soluble radioactivity from either 3H-labelled proteins transported by rapid axonal transport (AXT) or 3H-labelled ganglionic proteins. In nerve homogenates containing transported substrates, protease activity exhibited two peaks, one around pH 5 and one around pH 8. Ca2+ at 100 microM or higher concentrations only stimulated the latter, which was inhibited by 1 mM parachloromercuric benzoate, a sulphydryl reagent, but unaffected by ATP (1 mM). The proteolytic activity was recovered in the 10(5) g supernatant of the homogenate. In desheathed nerves containing 3H-labelled transported proteins, the protease activity could be activated by exposing the nerve to a Ca2+-ionophore, X-537 A, or to an elevated Ca2+-concentration (50 mM). These conditions were also shown to increase the influx and efflux of 45Ca2+ in the nerves. The results indicate the presence within axons of a Ca2+-activated soluble protease, which degrades rapidly transported proteins. The finding that the protease degraded ganglionic soluble proteins to about the same extent suggests a broad substrate specificity. The present system should be useful for further characterization of protease activity during various physiological conditions. | Chloromercuribenzoates |
The age-related testicular effect on the ovarian primordia was studied by combined transplantation of fetal testes and ovaries in adult male hosts. First, ovarian primordia of 14-day fetal rats were transplanted into a renal subcapsular position of castrated or intact adult male rats. In both the castrated and the intact hosts, most of the ovarian transplants developed normally with only 3 of them having in part seminiferous tubule-like structures in addition to normal ovarian structure. Second, a 14-day ovary was combined with a fetal testis the age of which varied from 13- to 18-day, and the combination was transplanted. In the combination of a 14-day ovary and a 13-day testis, the results varied in such a way that the ovary or the testis alone developed or otherwise, both gonads developed well. In union with 15- to 18-day testes, the ovaries did not develop, although the testes developed well. These results suggest that the 14-day ovarian primordia have a slight reactiveness to androgens of host rats and that the 13-day fetal testes begin to inhibit the development of the 14-day ovaries co-transplanted with them. | Fetal Tissue Transplantation |
The Cannabinoid CB1 Receptor (CB1R) is involved in a variety of physiological pathways and has long been considered a golden target for therapeutic manipulation. A large body of evidence in both animal and human studies suggests that CB1R antagonism is highly effective for the treatment of obesity, metabolic disorders and drug addiction. However, the first-in-class CB1R antagonist/inverse agonist, rimonabant, though demonstrating effectiveness for obesity treatment and smoking cessation, displays serious psychiatric side effects, including anxiety, depression and even suicidal ideation, resulting in its eventual withdrawal from the European market. Several strategies are currently being pursued to circumvent the mechanisms leading to these side effects by developing neutral antagonists, peripherally restricted ligands, and allosteric modulators. In this review, we describe the progress in the development of therapeutics targeting the CB1R in the last two decades." | Cannabinoid Receptor Antagonists |
The mineral sulfide-oxidising Acidithiobacillus ferrooxidans has been extensively studied over many years but some fundamental aspects of its metabolism remain uncertain, particularly with regard to its anaerobic oxidation of sulfur. This label-free, liquid chromatography-electron spray ionisation-mass spectrometry-based proteomic analysis estimated relative protein abundance during aerobic and anaerobic growth of At. ferrooxidans. One of its two bc1 complexes, that encoded by the petII operon, was strongly implicated in anaerobic ferric iron-coupled sulfur oxidation, probably in conjunction with two cytochromes. These two cytochromes are homologs of the Cyc2 and Cyc1 proteins that are involved in ferrous iron oxidation. The previously undetected cytochromes apparently associated with anaerobic growth in At. ferrooxidans appear to be absent in many other ferrous iron-oxidising acidophiles that can also reduce ferric iron, which suggests a diversity in the ferric-iron-coupled sulfur oxidation pathways. For aerobic growth of At. ferrooxidans, this analysis was consistent with the generally accepted mechanism for its oxidation of ferrous iron. Unexpectedly, proteins encoded by the petI operon were not abundant and generally not detected in the proteomic analyses of cells grown aerobically on sulfur, although there was some expression of genes of the petI and petII operons in these cells. | Acidithiobacillus |
Acute hematogenous peripelvic infections are common in tropical climates. However, in more temperate regions, this is a rare and often overlooked diagnosis. Because of the subtle and subacute nature of the symptoms, the diagnosis is often delayed. We report our experience with nine children treated for a hematogenous peripelvic infection. The hospital and clinic charts were reviewed of nine consecutive patients with the diagnosis of a peripelvic abscess. Patients ranged in age from 2 to 13 years. Symptoms were present from 5 to 20 days. The most consistent symptom was a hip-flexion pseudocontracture (eight patients). The initial diagnosis was correct in only three patients. Computed tomography (CT) scan was diagnostic in all nine patients, providing diagnosis and localization. Seven of the nine patients underwent irrigation and debridement followed by a variable course of intravenous (i.v.) and oral antibiotics. All seven had rapid resolution of their symptoms. Two patients were treated with i.v. antibiotics alone, one of whom had a recurrence of symptoms. All nine patients had microbiologic confirmation of the infecting organisms [seven at surgery, one from blood cultures, one from sacroiliac (SI) joint aspiration]. Eight of the nine were infected by Staphylococcus aureus and one by group A Streptococcus. All had complete resolution of their symptoms at follow-up. Although acute retrofascial abscesses are rare in temperate climates, they should be considered in the differential diagnosis in the child with lower abdominal or hip pain. CT scan was the most helpful diagnostic test in these patients. Surgical drainage resulted in the most consistent results in this small series of patients. | Abscess |
Rheumatic fever and rheumatic heart disease continue to be major public health problems in the developing world, particularly in the countries of sub-Saharan Africa. Because of its cost effectiveness, secondary prophylaxis is advocated as the principal means of disease prevention and control. However, in developing countries, valvular damage, due to earlier, unrecognized episodes of rheumatic fever, has already occurred by the time secondary prophylaxis is instituted. Secondary prophylaxis cannot reduce the incidence of new cases of rheumatic fever and has not been shown to alter the natural history of rheumatic valvular disease. Experience from several regions of the world suggests that incorporation of a strategy of primary antibiotic prophylaxis into a comprehensive program for disease control can reduce the incidence of rheumatic fever and rheumatic heart disease. In this article, we argue that a strategy of primary antibiotic prophylaxis, with appropriate modifications, can be successfully implemented in resource-poor settings across the world and should be a key component of any rheumatic heart disease control program. This, we believe, is essential for reducing the global burden of rheumatic heart disease. | Rheumatic Fever |
Postglycosylation acetylation of sialic acid imparts unique roles to sialoglycoconjugates in mammalian immune response making structural and functional understanding of these analogues important. Five partially O-acetylated Neu5Ac analogues have been synthesized. Reaction of per-O-silylated Neu5Ac ester with AcOH and Ac2O in pyridine promotes regioselective silyl ether/acetate exchange in the following order: C4 (2 degrees ) > C9 (1 degrees ) > C8 (2 degrees ) > C2 (anomeric). Subsequent hydrogenolysis affords the corresponding sialic acid analogues as useful chemical biology tools. | N-Acetylneuraminic Acid |
Using traditional weight-loss tests, as well as different electrochemical techniques (potentiodynamic polarization and electrochemical impedance spectroscopy), we investigated the corrosion-inhibition performance of 2,2'-(1,4-phenylenebis(methanylylidene)) bis(N-(3-methoxyphenyl) hydrazinecarbothioamide) (PMBMH) as an inhibitor for mild steel in a 1 M hydrochloric acid solution. The maximum protection efficacy of 0.0005 M of PMBMH was 95%. Due to the creation of a protective adsorption layer instead of the adsorbed H2O molecules and acidic chloride ions, the existence of the investigated inhibitor reduced the corrosion rate and increased the inhibitory efficacy. The inhibition efficiency increased as the inhibitor concentration increased, but it decreased as the temperature increased. The PMBMH adsorption mode followed the Langmuir adsorption isotherm, with high adsorption-inhibition activity. Furthermore, the value of the âÂÂGadso indicated that PMBMH contributed to the physical and chemical adsorption onto the mild-steel surface. Moreover, density functional theory (DFT) helped in the calculation of the quantum chemical parameters for finding the correlation between the inhibition activity and the molecular structure. The experimental and theoretical findings in this investigation are in good agreement. | Steel |
Linezolid is the first member of a new generation of antibiotics, the synthetic oxazolidinones, to become available, with a broad spectrum of in vitro activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and vancomycin-resistant E. faecium. Linezolid is showing great promise currently for the treatment of multiresistant gram-positive bacterial infections, especially complicated skin infections, catheter-induced bacteremia or nosocomial pneumonia both in the community and in a hospital setting, in children and in adults. Although most recent reports are favorable and anticipatory of a more extensive use of linezolid in appropriately selected pediatric population groups in the near future, following treatment failure of conventional antimicrobial agents, more clinical trials are, however, required to investigate the safety profile and tolerability of this new antibiotic in the pediatric population. | Oxazolidinones |
Mechanical stimulation is known to be an essential factor in the regulation of cartilage metabolism. We tested the hypothesis that expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1 to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the addition of 10 microg/mL oxidized low density lipoprotein (ox-LDL) (2.4 times control). Application of the cyclic load to the chondrocytes along with 10 microg/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3 times control. Individual application of cyclic loading and 10 microg/mL ox-LDL significantly suppressed chondrocytes viability (84.6% +/- 3.4% and 80.9% +/- 3.2% of control at 24 h, respectively; n = 3; p < 0.05) and proteoglycan synthesis [81.0% +/- 7.1% and 85.7% +/- 5.2% of control at 24 h, respectively; p < 0.05 when compared with 94.6% +/- 4.6% for native-LDL (n = 3)]. Cyclic loading and 10 microg/mL ox-LDL synergistically affected cell viability and proteoglycan synthesis, which were significantly suppressed to 45.6% +/- 4.9% and 48.7% +/- 6.7% of control at 24 h, respectively (n = 3; p < 0.01 when compared with individual application of cyclic loading or 10 microg/mL ox-LDL). In this study, we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis in chondrocytes, which may be mediated through enhanced expression of LOX-1 and which has important implications in the progression of cartilage degeneration in osteoarthritis. | Receptors, Oxidized LDL |
This article discusses exercise physiology and its application in the pediatric population. This article discusses exercise physiology and its application in the pediatric population. The authors briefly review the normal physiologic response to exercise. They then discuss populations in which exercise testing is most useful, the indications and contraindications for graded exercise, and the usual parameters that are measured during testing. Finally, the authors review some of the recent data on exercise performance in specific pediatric populations. | Exercise Test |
Although intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) play a relevant role in atherosclerosis, little is known about the prognostic impact of their soluble forms (s) in patients with peripheral arterial disease (PAD). The aim of this prospective study was to verify whether plasma levels of sICAM-1 and sVCAM-1 predict cardiovascular risk in PAD, and improve the prognostic value of the ankle/brachial index (ABI) alone. Accordingly, plasma levels of sICAM-1 and sVCAM-1, and the ABI were measured in 75 PAD patients who were monitored for a mean of 24+/-13 months. Twenty-two (29.3%) patients had a cardiovascular event (15 coronary, 3 cerebrovascular and 4 peripheral events). Plasma levels of sVCAM-1 were 618+/-258 ng/mL in patients with and 496+/-164 ng/mL in those without an event (p=0.016). The corresponding sICAM-1 values were 344+/-239 ng/mL and 275+/-99 ng/mL (p=0.079). The cardiovascular event rate was higher in patients with sVCAM-1 levels above the median than in those with sVCAM-1 below the median (p=0.0027 by log rank test). Independent predictors of events were sVCAM-1 levels above the median (p=0.005) and an ABI below the median (p=0.001). Amongst patients with ABI below the median, the occurrence of sVCAM-1 above the median was associated with a 3.4-fold increase in risk (95% CI 1.308 to 9.573, p=0.013). In conclusion, increased plasma levels of sVCAM-1 have a negative prognostic impact in PAD and improve the predictive value of ABI, which is currently the most powerful risk indicator in these patients." | Vascular Cell Adhesion Molecule-1 |
Mushrooms have been attracting attention as a source of bioactive compounds for the development of dietary supplements and medicines. Many researchers have reported pharmacological effects of edible mushrooms, and have isolated and identified bioactive substances. Lentinula edodes (shiitake) and Flammulina velutipes (enokitake) are the cultivated edible mushrooms that are popular throughout the world. In L. edodes, polyacetylenes and sulfur compounds have been shown to display antimicrobial activity. In F. velutipes, many types of bioactive terpenes have been reported from mycelium culture filtrate or solid culture substrate. This article reviews the bioactive metabolites of low-molecular weight from L. edodes and F. velutipes. | Flammulina |
Importance of left atrial (LA) phasic function evaluation is increasingly recognized for its incremental value in terms of prognosis and risk stratification. LA phasic deformation in the pathway of normal aging has been characterized using echocardiographic speckle tracking. However, no data are available regarding age-related variations using feature-racking (FT) techniques from standard cine magnetic resonance imaging (MRI). We studied 94 healthy adults (41 +/- 14 yr, 47 women), who underwent MRI and Doppler echocardiography on the same day for left ventricular (LV) diastolic function evaluation. From cine MRI, longitudinal strain and strain rate, radial motion fraction, and radial relative velocity, respectively, corresponding to the reservoir, conduit, and LA contraction phases, were measured using dedicated FT software. Longitudinal strain and radial motion fraction decreased gradually and significantly with aging for both reservoir (r > 0.31, P < 0.003) and conduit (r > 0.54, P < 0.001) phases, whereas they remained unchanged during the LA contraction phase. Subsequently, the LA contraction-to-reservoir ratio increased significantly with age (r > 0.44, P < 0.001). Longitudinal strain rate and radial relative velocity significantly decreased with age (reservoir: r = 0.39, P < 0.001, conduit: r > 0.54, P < 0.001), and these associations tended to be stronger in women than in men. Finally, associations of LA functional indexes with age were stronger in individuals with lower transmitral early-to-atrial maximal velocity ratio and mitral annulus maximal longitudinal velocity, as well as higher transmitral early maximal-to-mitral annulus maximal longitudinal velocity ratio, highlighting the LV-LA interplay. Age-related changes in LA phasic function indexes were quantified by cine MRI images using a FT technique and were significantly related to age and LV diastolic function. | Heart Atria |
Ten strains isolated from sick dogs in 1998 in St. Petersburg were studied by traditional and molecular biological methods of Brucella identification. PCR study confirmed that the isolated cultures were Brucellae, and comparative study of the traditional phenotypical characteristics and protein and antigenic composition allowed referring all the isolated strains to B. canis. Traditional identification showed similarity of 7 strains with the reference B. canis strain RM6/66, and 3 strains were similar to B. canis Mex 51 strain. These results confirmed the division of B. canis into two biovars. Polyacrylamide gel electrophoresis with sodium dodecyl sulfate demonstrated the identity of protein profiles of 10 strains isolated from dogs to the reference B. canis RM6/66 strain. Immunoblotting analysis with S- and R-specific rabbit antisera also demonstrated the identity of antigens binding IgG antibodies in the strains isolated from dogs to the reference B. canis RM6/66 strain. | Brucellaceae |
Immune checkpoint inhibitor (ICI) responses vary, and biomarkers for predicting responders are urgently needed. Growing evidence points to the association between programmed cell death protein ligand 2 (PDL2) and ICI benefits, while clinical evidences were lacking. Thus, we consolidated five public ICI-treated cohorts to investigate the association between PDL2 expression and ICI treatment prognosis. Immune cell signatures and IFN-gamma signatures are investigated in The Cancer Genome Atlas (TCGA) dataset and later in ICI-treated cohorts to explore the association between PDL2 and antitumor immunity in the tumor microenvironment (TME). We found that immune cell signatures and IFN-gamma signatures were enriched in the PDL2-high group in TCGA pooled cohorts and most cancers. Consistently, in ICI-treated cohorts, patients with high PDL2 expression experienced longer overall survival time (OS) and were more likely responsive to ICIs than patients with low PDL2 expression. Immune cell scores of the high PDL2 expression patients were significantly higher (P < 0.05) than those of the low PDL2 expression patients in ICI-treated cohorts. In conclusion, our findings suggest that PDL2 is a potential predictive biomarker for ICIs." | Programmed Cell Death 1 Ligand 2 Protein |
The interest in the pedunculopontine tegmental nucleus (PPTg), a structure located in the brainstem at the level of the pontomesencephalic junction, has greatly increased in recent years because it is involved in the regulation of physiological functions that fail in Parkinson's disease and because it is a promising target for deep brain stimulation in movement disorders. The PPTg is highly interconnected with the main basal ganglia nuclei and relays basal ganglia activity to thalamic and brainstem nuclei and to spinal effectors. In this review, we address the functional role of the main PPTg outputs directed to the basal ganglia, thalamus, cerebellum and spinal cord. Together, the data that we discuss show that the PPTg may influence thalamocortical activity and spinal motoneuron excitability through its ascending and descending output fibers, respectively. Cerebellar nuclei may also relay signals from the PPTg to thalamic and brainstem nuclei. In addition to participating in motor functions, the PPTg participates in arousal, attention, action selection and reward mechanisms. Finally, we discuss the possibility that the PPTg may be involved in excitotoxic degeneration of the dopaminergic neurons of the substantia nigra through the glutamatergic monosynaptic input that it provides to these neurons." | Pedunculopontine Tegmental Nucleus |
AIM OF THE STUDY: The purpose of our study was the evaluation of the effect of 2,000 mg levetiracetam monotherapy over a 3-month period on nocturnal sleep in patients with epilepsy. CLINICAL RATIONALE: Levetiracetam (LEV) is a novel antiepileptic drug with a unique anticonvulsive mechanism of action. It has been commonly reported to cause sleep disruption and daytime sleepiness in epilepsy patients. Its advantages (its broad antiepileptic spectrum, optimal pharmacokinetics, good safety and tolerability) have led to its frequent use in clinical practice, although little is yet known about LEV's effect on nocturnal sleep architecture. MATERIAL AND METHODS: The effect of LEV on nocturnal sleep was assessed through a full-night lab polysomnography (PSG), followed by a four-nap multiple sleep latency test. Both procedures were performed at baseline and after three months of LEV treatment. The dynamics of seven main PSG variables was evaluated prior to, and three months after, LEV therapy. RESULTS: Twenty five patients with newly diagnosed or untreated epilepsy completed the study. We found no statistically significant difference at baseline and after LEV therapy in the following sleep parameters: total sleep time, sleep onset, wake after sleep onset, N1 stage and rapid eye movement (REM) sleep (minutes and percentages), and latency of all sleep stages including REM sleep. However, we found a statistically significant increase in the number of awakenings and arousals, an increase in N2 and a decrease in N3 stages (minutes and percentages) after therapy. We also observed an increase in N1 stage and a trend toward a reduction in REM sleep (in both minutes and percentages), but they did not reach statistical significance. CONCLUSIONS: Levetiracetam 2,000 mg/day does not affect sleep continuity and may be considered a sleep-friendly antiepileptic drug. | Levetiracetam |
The POU proteins BRN-3a, -3b and -3c are transcription factors encoded by separate genes that are differentially expressed during neural development. Comparison of genomic and cDNA sequences revealed similar exon/intron structures for Brn-3a and -3c genes, whereas the Brn-3b gene appeared to contain an intronless coding region. Fluorescence in situ hybridization experiments with mouse chromosomes showed that Brn-3a maps to mouse chromosome 14E1-3, Brn-3b to XF1-5 and Brn-3c to 18B3-E1. | Transcription Factor Brn-3 |
In live cells, phase separation is thought to organize macromolecules into membraneless structures known as biomolecular condensates. Here, we reconstituted transcription in condensates from purified mitochondrial components using optimized in vitro reaction conditions to probe the structure-function relationships of biomolecular condensates. We find that the core components of the mt-transcription machinery form multiphasic, viscoelastic condensates in vitro. Strikingly, the rates of condensate-mediated transcription are substantially lower than in solution. The condensate-mediated decrease in transcriptional rates is associated with the formation of vesicle-like structures that are driven by the production and accumulation of RNA during transcription. The generation of RNA alters the global phase behavior and organization of transcription components within condensates. Coarse-grained simulations of mesoscale structures at equilibrium show that the components stably assemble into multiphasic condensates and that the vesicles formed in vitro are the result of dynamical arrest. Overall, our findings illustrate the complex phase behavior of transcribing, multicomponent condensates, and they highlight the intimate, bidirectional interplay of structure and function in transcriptional condensates. | Nuclear Bodies |
BACKGROUND: Retinoic acid receptor (RAR) activation induces cell differentiation and may antagonize cancer progression. Cellular retinol-binding protein I (CRBP-I) functions in retinol storage and its expression is lower in human cancers than in normal cells. We hypothesized that retinol storage might be linked to RAR activation and thus that lowered CRBP-I function might impair RAR activity and cell differentiation. METHODS: Sarcoma virus 40-immortalized human mammary epithelial cells (MTSV1-7) devoid of CRBP-I were transfected with wild-type CRBP-I or CRBP-I point mutants with low RA binding affinity. The subcellular localization of CRBP-I was investigated in these cells and in wild-type or CRBP-I null mouse mammary epithelial cells (MECs), using indirect immunofluorescence and sucrose gradient fractionation. RAR activity was assessed using reporter gene assays. Acinar differentiation and in vivo tumor growth were assessed in reconstituted basement membrane and athymic mice, respectively. RESULTS: In cells expressing wild-type CRBP-I but not the CRBP-I mutants, CRBP-I was found mainly in lipid droplets, the retinol storage organelle, and this localization was associated with promotion of retinol storage by wild-type CRBP-I only. RAR activity was higher and acinar differentiation was observed in cells expressing wild-type but not mutant CRBP-I. RAR antagonist treatment blocked and chronic RA treatment mimicked, the CRBP-I induction of cell differentiation. Finally, CRBP-I suppressed tumorigenicity in athymic mice. CONCLUSIONS: Physiologic RAR activation is dependent on CRBP-I-mediated retinol storage, and CRBP-I downregulation chronically compromises RAR activity, leading to loss of cell differentiation and tumor progression." | Retinol-Binding Proteins, Cellular |
Objective: To understand the epidemiological characteristics of suspected occupational diseases cases, and to track the subsequent diagnosis of suspected cases in Hubei Province from 2020 to 2021, and to provide theoretical basis for the supervision of suspected occupational diseases. Methods: In April 2022, the data of suspected occupational diseases cases and occupational diseases in Hubei Province from 2020 to 2021 were collected by the Occupational Diseases and Health Risk Factors Information Surveillance System. The distribution and diagnosis of suspected occupational diseases cases were analyzed. We investigated undiagnosed suspected occupational diseases by telephone. Results: From 2020 to 2021, a total of 1872 cases of suspected occupational diseases in 6 categories and 18 species were reported in Hubei Province. The top three suspected occupational diseases were suspected occupational noise deafness (36.75%, 688/1872), suspected coal worker's pneumoconiosis (33.07%, 619/1872) and suspected silicosis (20.99%, 393/1872). The diagnosis rate of suspected occupational diseases was 33.60% (629/1872). The rate of confirmed diagnosis was 63.59% (400/629). The diagnosis rate (26.86%, 456/1698) and rate of confirmed diagnosis (55.48%, 253/456) of suspected occupational diseases detected by occupational health examination were the lowest. The diagnosis rate of suspected occupational diseases detected by comprehensive medical institutions and private medical institutions were lower than disease prevention and control institutions and occupational disease prevention center (P<0.05). The main reasons for not entering the diagnostic procedure included that workers were not informed that they were diagnosed as suspected occupational diseases (31.55%, 124/393), workers were unwilling to apply for occupational disease diagnosis (18.56%, 73/393), and some workers planned to apply for diagnosis but had not yet applied (10.69%, 42/393) . Conclusion: Occupational noise deafness, coal worker's pneumoconiosis and silicosis are the main diseases of suspected occupational diseases in Hubei Province. In order to increase the diagnosis rate and confirmed diagnosis rate of suspected occupational diseases, it is suggested to strengthen management and supervision from the aspects of case management, information warning and worker notification. | Anthracosis |
The ICH M7 Option 4 control of (potentially) mutagenic impurities is based on the use of scientific principles in lieu of routine analytical testing. This approach can reduce the burden of analytical testing without compromising patient safety, provided a scientifically rigorous approach is taken which is backed up by sufficient theoretical and/or analytical data. This paper introduces a consortium-led initiative and offers a proposal on the supporting evidence that could be presented in regulatory submissions. | Mutagenicity Tests |
Objectives The few studies of shift work and late life cognitive functioning have yielded mixed findings. The aim of the present study is to estimate the association between shift-work experience and change in cognitive performance before and after retirement age among older adults who were gainfully employed. Methods Five hundred and ninety five participants with no dementia were followed up for a mean of 17.6 standard deviation (SD) 8.8 years from a Swedish population-based sample. Participants had self-reported information on any type of shift-work experience (ever/never) in 1984 and measures of cognitive performance (verbal, spatial, memory, processing speed, and general cognitive ability) from up to 9 waves of cognitive assessments during 1986-2012. Night work history (ever/never) from 1998-2002 was available from a subsample (N=320). Early adult cognitive test scores were available for 77 men. Results In latent growth curve modeling, there were no main effects of any-type" or night shift work on the mean scores or rate of change in any of the cognitive domains. An interaction effect between any-type shift work and education on cognitive performance at retirement was noted. Lower-educated shift workers performed better on cognitive tests than lower-educated day workers at retirement. Sensitivity analyses, however, indicated that the interactions appeared to be driven by selection effects. Lower-educated day workers demonstrated poorer cognitive ability in early adulthood than lower-educated shift workers, who may have selected jobs entailing higher cognitive demand. Conclusion There was no difference in late-life cognitive aging between individuals with a history of working shifts compared to those who had typical day work schedules during midlife." | Cognitive Aging |
This paper presents a new method for site-specific labelling of antibodies employing enzymatic reactions without oxidizing or reducing agents. IgG was first treated with immobilized sialidase from Clostridium perfringens to cleave bound NeuAc. CMP-9-deoxy-9-salizoyl-NeuAc, an activated sialic acid analogue, was labelled with 131I via the iodogen-method in high yields (> 95%). Then the oligosaccharide chains of antibodies were labelled yield with the radioactive NeuAc analogue by transfer using alpha-2,6-sialyltransferase from rat liver in 50%." | beta-D-Galactoside alpha 2-6-Sialyltransferase |
Previous studies reported that virtual reality (VR)-based exposure therapy (VRET) was a clinically beneficial intervention for specific phobias. However, among VRET, VR-based graded exposure therapy (VR-GET) is little known about its efficacy on posttraumatic stress disorder (PTSD) symptoms. Therefore, this meta-analysis investigated the effects of VR-GET for PTSD symptoms. A literature search yielded seven randomized controlled trials. The differences between conditions regarding the primary outcome of PTSD symptoms in the effect size of the individual study were calculated using Hedges' g. The findings showed VR-GET showed a significantly larger effect size for PTSD symptoms (g = 1.100, p = 0.001), compared to controls. However, no significant difference between conventional VRET and controls was found for PTSD symptoms (g = -0.279, p = 0.970). These findings indicated the superiority of VR-GET for PTSD symptoms compared to controls, supporting the importance of immersive PTSD treatments. Nevertheless, the results need to be interpreted with caution due to the substantial number of military service personnel studies. Future trials, considering individually tailored scenarios in virtual environments to cover a wider range of trauma types, are required to investigate its evidence on treating PTSD. | Implosive Therapy |
We report the development of a unique radioimmunoassay (RIA) for rat insulin-like growth factor-I (rIGF-I) which does not recognize human IGF-I (hIGF-I). The rIGF RIA uses a specific anti-rIGF-I antiserum with rIGF-I standards and radioligand. Rat sera were extracted by either an abbreviated acid/ethanol procedure or by acid-chromatography with virtually identical results. Assay sensitivity is congruent to 0.5 ng/tube and inter- and intra-assay coefficients of variation were 3.4-7.6% and 4.8-9.2%, respectively. Comparisons of the rIGF-I RIA with a typical heterologous RIA shows that the latter underestimates rIGF-I levels congruent to of 3-fold. Sera from rats treated with hIGF-I were also studied using the rIGF-I RIA and a hIGF-I- specific immunoradiometric assay (IRMA), and results indicate poor correlation between the actual total IGF-I levels (rIGF-I RIA + hIGF-IRMA) and the heterologous RIA estimates. The availability of both rIGF-I and hIGF-I specific immunoassays facilitates more precise studies of hIGF-I in the rat model. | Radioimmunoassay |
A protocol for the isolation and long-term propagation of adult rat Sertoli cells (SCs) using conditional reprogramming (CR) was developed and the formation of tight junctions as an in vitro model for the blood testis barrier (BTB) was studied. Three pure primary SC lines were isolated successfully and maintained for several months without significant changes in expression levels of SC-typical markers such as SRY-box transcription factor 9 (SOX9), transferrin, clusterin, androgen receptor (AR), and GATA binding protein 1 (GATA1). In addition to AR expression, the tight junction proteins, zonula occludens-1 (ZO-1) and the junctional adhesion molecule-3 (JAM-3), were upregulated and the SC barrier integrity was enhanced by testosterone. Peritubular/myoid cells did not increase the tightness of the SC. The cytokines, interleukin-6 (IL-6), bone morphogenetic protein-2 (BMP2), and transforming growth factor beta-3 (TGF-beta3), negatively affected the tightness of the SC barrier. We have established a protocol for the isolation and long-term propagation of highly pure primary adult rat SCs, which are able to respond to androgen treatments, to form tight junctions and to maintain the mRNA expression of SC-specific genes. By applying this new method, adult SCs can now be analyzed in more detail and might serve as an in vitro model for the study of many SC functions. | Testis |
Trypanosoma brucei is an important human pathogen. In this study, we have focused on the characterization of FtsH protease, ATP-dependent membrane-bound mitochondrial enzyme important for regulation of protein abundance. We have determined localization and orientation of all six putative T.brucei FtsH homologs in the inner mitochondrial membrane by in silico analyses, by immunofluorescence, and with protease assay. The evolutionary origin of these homologs has been tested by comparative phylogenetic analysis. Surprisingly, some kinetoplastid FtsH proteins display inverted orientation in the mitochondrial membrane compared to related proteins of other examined eukaryotes. Moreover, our data strongly suggest that during evolution the orientation of FtsH protease in T. brucei varied due to both loss and acquisition of the transmembrane domain. | Euglena longa |
Cancer is still one of the major causes of death worldwide. Radiation therapy and chemotherapy remain the main treatment modalities in cancer. These therapies exert their effect mainly through interference with DNA replication and induction of DNA damage. It is believed that one way of improving the efficacy of cancer treatment will be to inhibit the replication stress and DNA damage responses and promote mitotic catastrophe of cancer cells. So far, the majority of the efforts have focused central players of checkpoint responses, such as ATR and CHK1, and DNA damage repair, such as PARPs. Being a key player in the replication stress response, checkpoint activation, and the DNA damage response, Claspin constitutes an attractive therapeutic target in cancer, namely for radio- and chemo-sensitization. In this review, we will go through Claspin functions in the replication stress and DNA damage responses and will discuss how Claspin can be targeted in cancer treatment, as well as the effects of Claspin inhibition." | Adaptor Proteins, Signal Transducing |
The detection of metastasizing single tumor cells has so far been difficult. Using a monoclonal antibody (MAb A45-B/B3) recognizing human cytokeratin, we identified immunocytochemically single tumor cells and micrometastases in patients (n = 24) with nonsmall cell lung cancer at the time of surgery of the primary tumor. The cytokeratin-positive cells (1-14/5 x 10(5) cells) in the bone marrow samples of 9 (9/24) patients were found. We also found a garland-like cluster, which consists of seven cancer cells and two closely connected tumor cells from one bone marrow sample. These results indicate that this technique can be used as a early diagnostic technique of bone marrow micrometastasis in the patient with the nonsmall cell lung cancer. | Bone Marrow Neoplasms |
We made use of a peculiar therapeutic practice in a congenital bullous ichthyosiform erythroderma case, which allowed a favourable clinical course and a quick recovery without scared results. We utilized a new skin substitute together with air-fluidized bed, just lonely used in other diseases." | Ichthyosiform Erythroderma, Congenital |
Aim: To pilot a 4-week regional anesthesia curriculum for limited-resource settings. Intervention: A baseline needs assessment and knowledge test were deployed. The curriculum included lectures and hands-on teaching, followed by knowledge attainment tests. Results: Scores on the knowledge test improved from a mean of 37.1% (SD 14.7%) to 50.9% (SD 18.6%) (p = 0.017) at 4 weeks and 49% at 24 months. An average of 1.7 extremity blocks per month was performed in 3 months prior to the curriculum, compared with an average of 4.1 per month in 8 months following. Conclusion: This collaborative curriculum appeared to have a positive impact on the knowledge and utilization of regional anesthesia. | Capacity Building |
Global habitat fragmentation is associated with the emergence of infectious diseases of wildlife origins in human populations. Despite this well-accepted narrative, the underlying mechanisms driving this association remain unclear. We introduce a nuanced hypothesis, the 'coevolution effect'. The central concept is that the subdivision of host populations which occurs with habitat fragmentation causes localized coevolution of hosts, obligate parasites, and pathogens which act as 'coevolutionary engines' within each fragment, accelerating pathogen diversification, and increasing pathogen diversity across the landscape. When combined with a mechanism to exit a fragment (e.g., mosquitoes), pathogen variants will spill over into human communities. Through this combined ecoevolutionary approach we may be able to understand the fine-scale mechanisms that drive disease emergence in the Anthropocene. | Zoonoses |
Mirtazapine has a low affinity for 5-HT(1A) receptors but shows 5-HT(1A)-agonistic-like effects in behavioral pharmacology test. However, there is to date no clear evidence that mirtazapine enhances 5-HT(1A) neurotransmission. The object of the present study was to assess the effects of mirtazapine on dialysate levels of dopamine and 5-HT in the medial frontal cortex of freely moving rats and to determine whether this drug could modulate 5-HT(1A) neurotransmission. In vivo microdialysis was used to study the effects of mirtazapine on extracellular dopamine and 5-HT levels, and the effect of the 5-HT(1A) antagonist WAY100,356 on extracellular dopamine level increased by mirtazapine in the rat prefrontal cortex. Mirtazapine (4-16 mg/kg, i.p.) produced a dose-dependent increase in extracellular dopamine levels in the medial prefrontal cortex (mPFC) of freely moving rats without modifying those of 5-HT. In the presence of the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazineyl]ethyl]-N-(pyridinyl)-cyclohexane-carboxamide (WAY100,635; 0.3 mg/kg; i.p.), the influence of mirtazapine on cortical levels of dopamine was markedly attenuated. These results indicate that mirtazapine induces the enhancement of the output of cortical dopamine mediated via blockade of alpha(2)-adrenergic receptors and facilitation of post-synaptic 5-HT(1A) function. | Receptor, Serotonin, 5-HT1A |
Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular sensor that detects small peptides derived from the cell wall component of intestinal microflora. NOD1 is expressed in both non-hematopoietic cells such as epithelial cells and hematopoietic cells such as antigen-presenting cells. Detection of its ligand by NOD1 leads to innate immune responses through activation of nuclear factor kappa B and type I interferon as well as induction of autophagy. Innate immune responses through NOD1 activation play an indispensable role both in host defense against microbial infection and in the development of gastrointestinal disorders. Of particular importance, NOD1-mediated innate immune responses are associated with mucosal host defenses against Helicobacter pylori (H. pylori) infection of the stomach and with the development of pancreatitis. In this review, we discuss the molecular mechanisms by which NOD1 activation leads to the development of H. pylori-related gastric diseases and pancreatitis." | Nod1 Signaling Adaptor Protein |
We investigated in this study the influence of an endophytic fungus, Paecilomyces formosus LHL10, on the thermotolerance of cucumber (Cucumis sativus) upon exposure to high (38 degrees C) and low (8 degrees C) temperature stresses. The results showed that endophyte-inoculated plants had significantly higher plant growth attributes under high-temperature stress. However, they were either low or insignificant in non-inoculated control and inoculated plants with 8 degrees C treatments. Lower stress-promulgated water deficit and cellular membrane damage were observed in endophyte-treated plants after 38 degrees C treatment than in control plants under 8 degrees C stress. Total polyphenol, reduced glutathione, and lipid peroxidation activities were reduced in endophyte-associated plants after exposure to 38 degrees C as compared with control and 8 degrees C-treated plants. The concentration of saturated fatty acids (palmitic-C16:0; stearic-C18:0) was lower in endophyte-treated plants with or without low-temperature stress, but after 8 degrees C treatment increased compared with controls. Unsaturated fatty acids (oleic-C18:1; linoleic-C18:2; linolenic-C18:3 acids) were similar at normal conditions; however, at 38 degrees C, C18:2 and C18:3 were decreased, and C18:1 was increased in endophyte-treated plants compared with controls, while the inverse relationship was found at 8 degrees C. Low levels of abscisic acid in P. formosus-associated plants after 38 degrees C treatments revealed stress tolerance compared with control and 8 degrees C-treated plants. In contrast, salicylic acid was pronounced in endophyte-treated plants after low-temperature stress as compared to other treatments. The results provide evidence that the response to P. formosus association was beneficial at normal growth temperature and had varying effects in response to temperature stress. | Cucumis sativus |
Human-carnivore conflict continues to present a major conservation challenge around the world. Translocation of large carnivores is widely implemented but remains strongly debated, in part because of a lack of cost transparency. We report detailed translocation costs for three large carnivore species in Namibia and across different translocation scenarios. We consider the effect of various parameters and factors on costs and translocation success. Total translocation cost for 30 individuals in 22 events was $80,681 (US Dollars). Median translocation cost per individual was $2,393, and $2,669 per event. Median cost per cheetah was $2,760 (n = 23), and $2,108 per leopard (n = 6). One hyaena was translocated at a cost of $1,672. Tracking technology was the single biggest cost element (56%), followed by captive holding and feeding. Soft releases, prolonged captivity and orphaned individuals also increased case-specific costs. A substantial proportion (65.4%) of the total translocation cost was successfully recovered from public interest groups. Less than half the translocations were confirmed successes (44.4%, 3 unknown) with a strong species bias. Four leopards (66.7%) were successfully translocated but only eight of the 20 cheetahs (40.0%) with known outcome met these strict criteria. None of the five habituated cheetahs was translocated successfully, nor was the hyaena. We introduce the concept of Individual Conservation Cost (ICC) and define it as the cost of one successfully translocated individual adjusted by costs of unsuccessful events of the same species. The median ICC for cheetah was $6,898 and $3,140 for leopard. Translocations are costly, but we demonstrate that they are not inherently more expensive than other strategies currently employed in non-lethal carnivore conflict management. We conclude that translocation should be one available option for conserving large carnivores, but needs to be critically evaluated on a case-by-case basis. | Carnivora |
Extraction of second molars as an orthodontic measure is a simple procedure which can lead to good clinical results. Indications as well as timing and long term effects on buccal occlusion are discussed. It is concluded that acceptable results may only be expected when the extraction is strictly indicated and carried out in cases when the third molars have reached their full crown stage but before radiographic evidence of root formation. Upper third molars with an angulation of less than 30 degrees and lower third molars with an angulation of 30-60 degrees to the occlusal plane are likely to give a satisfactory position after eruption. | Orthodontics, Interceptive |
Biological contamination of surfaces, both in industry and in health care, plays an important role as a potential vector of disease transmission. Metals have been described to be effective antibiofilm agents, and the efficacy of silver ions as a disinfectant has been known for centuries. The activity of AgNO3 combined with the lipopeptide biosurfactant V9T14 has been studied against a preformed Escherichia coli biofilm on the Calgary Biofilm Device. Results indicated that the activity of silver can be synergistically enhanced by the presence of V9T14, both allowing for a reduction in the quantity of silver used and for greater antimicrobial activity. The concentration of silver needed to obtain this reduction in the silver-biosurfactant solution was from 129- to 258-fold less than the concentration of silver alone. To our knowledge, this is the first time that a synergistic interaction between a lipopeptide biosurfactant and silver has been observed. | Silver Nitrate |
The PHA synthase structural gene of Thiocapsa pfennigii was identified and subcloned on a 2.8-kbp BamHI restriction fragment, which was cloned recently from a genomic 15.6-kbp EcoRI restriction fragment. Nucleotide sequence analysis of this fragment revealed three open reading frames (ORFs), representing coding regions. Two ORFs encoded for the PhaE (Mr 40,950) and PhaC (Mr 40,190) subunits of the PHA synthase from T. pfennigii and exhibited high homology with the corresponding proteins of the Chromatium vinosum (52.8% and 85.2% amino acid identity) and the Thiocystis violacea (52.5% and 82.4%) PHA synthases, respectively. This confirmed that the T. pfennigii PHA synthase was composed of two different subunits. Also, with respect to the molecular organization of phaE and phaC, this region of the T. pfennigii genome resembled very much the corresponding regions of C. vinosum and of Thiocystis violacea. A recombinant strain of Pseudomonas putida, which overexpressed phaE and phaC from T. pfennigii, was used to isolate the PHA synthase by a two-step procedure including chromatography on Procion Blue H-ERD and hydroxyapatite. The isolated PHA synthase consisted of two proteins exhibiting the molecular weights predicted for PhaE and PhaC. Hybrid PHA synthases composed of PhaE from T. pfennigii and PhaC from C. vinosum and vice versa were constructed and functionally expressed in a PHA-negative mutant of P. putida; and the resulting PHAs were analyzed. | Thiocapsa |
Bilateral striatal necrosis (BSN) has many causes and is characterized by unique clinical and neuroradiological features. Herein, we report a clinical and genetic analysis of three BSN cases from two independent Japanese families harboring a mitochondrial DNA (mtDNA) 14459G>A mutation located in a coding region of the NADH dehydrogenase subunit 6 gene. In the first family, two male siblings from non-consanguineous parents exhibited similar phenotypes, with infantile-onset generalized dystonia. A third sporadic case involved a male patient with a comparatively milder phenotype characterized by juvenile-onset mild truncal ataxia and parkinsonism. Cerebral magnetic resonance imaging of these cases revealed abnormal signal intensities along the bilateral putaminal area and enlarged lateral ventricle anterior horns caused by caudate nuclear atrophy, particularly in the sibling pair. The sibling-pair cases shared a homoplasmic 14459G>A mutation, and the sporadic case showed heteroplasmy of the same mutation. Additionally, all three cases harbored the 14605A>G single nucleotide polymorphism, which was previously reported as a rare synonymous variation (4.3%) in a Japanese population. Plasmid sequencing revealed a genetic linkage of these two DNA substitutions, suggesting that the three patients shared a genetic founder. Although our mtDNA analysis was only accessible using leukocytes, clinical severity might be associated with homoplasmy or heteroplasmy. In summary, it is important to evaluate potential mtDNA defects in BSN cases, regardless of familial occurrence. | Striatonigral Degeneration |
Multidrug therapy (MDT), according to the recommendations of a WHO Study Group of 1982, was introduced in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT), Ethiopia, in January 1983. Of 6042 paucibacillary patients who were put on MDT during a period of 7 years, 5485 patients (90.8%) completed the course of MDT; 437 patients (7.2%) did not fulfill the requirement for clinic attendance and either discontinued MDT themselves or the treatment was discontinued by the service. The remaining 120 patients (2.0%) either died, were transferred, left the control area or continued MDT after 9 months. The urine spot test for the presence of dapsone showed a significantly higher proportion of positive results for patients on MDT than for patients on dapsone. The analysis of the compliance with the prescribed doses of MDT showed that of 963 patients, 81.9% received six doses of MDT and 18.1%, more than six doses; 82.6% of these 963 patients attended with 100% regularity, 12.7%, 3.6%, and 1.1% missed one, two, or three clinic appointments, respectively, while fulfilling the requirement for overall clinic attendance. Of the 429 patients who had not been treated with dapsone before MDT, the skin lesions were clinically active at the time of stopping MDT in 130 patients (30.3%). In all, except one of the 114 patients (0.9%) who attended for follow-up examinations, the skin lesions had become clinically inactive within 2 years after stopping MDT. The recommended duration of MDT is discussed based on findings in the ALERT leprosy control programs and observations by others. | Leprosy, Paucibacillary |
We report on a 7-year-old immunocompetent boy initially presenting with right-sided frontal cephalalgia, painful ophthalmoplegia, and ptosis for 1 month. Initial cerebrospinal fluid analysis produced normal results. Magnetic resonance imaging revealed an inflammatory pseudotumor of the right cavernous sinus after intravenous gadolinium administration, indicating a rare idiopathic inflammatory disorder of the cavernous sinus, i.e., Tolosa-Hunt syndrome. Ptosis and cephalalgia resolved after steroid treatment, although right-sided ophthalmoplegia remained. Breakthrough headache, associated with signs of meningeal irritation, developed 6 weeks later. Follow-up contrast-enhanced computed tomography revealed no enhancing cavernous soft tissue mass. A further lumbar puncture disclosed central nervous system infection with Staphylococcus saprophyticus. After 6 weeks of vancomycin, the headache resolved completely, and neuroimaging produced normal results. A diagnosis of Tolosa-Hunt syndrome should be rendered cautiously, because the etiology may involve a rare but not idiopathic" infection. Moreover, if clinical signs are not fully responsive to steroid treatment, the underlying problems should receive careful investigation." | Staphylococcus saprophyticus |
Physician-owned specialty hospitals have flourished in today's healthcare arena, but also have been the subject of a great deal of controversy. The author argues that the rise of specialty hospitals has been the result of a confluence of two healthcare policies: (1) skewed DRG payment methodologies and (2) the misapplication of exemptions to the Stark Law's ban on physician self-referral. This Article examines the aspects of these healthcare policies that have allowed for the explosion of specialty hospitals, as well as the arguments for and against the creation and need for specialty hospitals. The Article also analyzes the reform proposals to correct the Stark and DRG methodologies and how those proposals will affect both specialty and general hospitals. | Physician Self-Referral |
Animals operate in complex environments, and salient social information is encoded in the nervous system and then processed to initiate adaptive behavior. This encoding involves biological embedding, the process by which social experience affects the brain to influence future behavior. Biological embedding is an important conceptual framework for understanding social decision-making in the brain, as it encompasses multiple levels of organization that regulate how information is encoded and used to modify behavior. The framework we emphasize here is that social stimuli provoke short-term changes in neural activity that lead to changes in gene expression on longer timescales. This process, simplified-neurons are for today and genes are for tomorrow-enables the assessment of the valence of a social interaction, an appropriate and rapid response, and subsequent modification of neural circuitry to change future behavioral inclinations in anticipation of environmental changes. We review recent research on the neural and molecular basis of biological embedding in the context of social interactions, with a special focus on the honeybee. | Social Interaction |
Arsenic (As) and lead (Pb) are frequently emitted from various sources into environment, but microbial responses to their combined toxicity have not been systematically investigated. In this study, Chlamydomonas reinhardtii was exposed to two levels of arsenate (As (V), 50, 500 mug/L), Pb (II) (500, 5000 mug/L) and their mixture (50 mug/L As (V) + 500 mug/L Pb (II); 500 mug/L As (V) + 5000 mug/L Pb (II)). The growth of C. reinhardtii was inhibited more remarkably by As (V) than by Pb (II). The As stress was alleviated by Pb in the 50 mug/L As (V) + 500 mug/L Pb (II) treatment, but was enhanced upon the 500 mug/L As (V) + 5000 mug/L Pb (II) exposure, with more pronounced changes in a number of physiological parameters of the algal cells. Proteomic results showed that 71 differently expressed proteins (DEPs) in the treatment of 50 mug/L As (V) + 500 mug/L Pb (II), and 167 DEPs were identified in that of 500 mug/L As (V) + 5000 mug/L Pb (II). These proteins were involved in energy metabolism, photosynthetic carbon fixation, reactive oxygen scavenging and defense, and amino acid synthesis. Taken together, these physiological and proteomic data demonstrated that C. reinhardtii could resist the As (V) and Pb (II) combined treatments through extracellular complexation and intracellular pathways. | Arsenates |
Gallotannin 1,2,6-tri-O-galloyl-beta-d-glucopyranose (1,2,6-TGGP) plays multiple roles against multidrug-resistant bacteria and other diseases. Nevertheless, its availability in tea (Camellia sinensis) has rarely been reported. Herein, the identification and verification of 1,2,6-TGGP from Camellia sinensis using ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-qTOF MS/MS), electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) were reported. The isolated 1,2,6-TGGP was used for the chemotaxonomy analysis of 17 tea cultivars. The contents of 1,2,6-TGGP ranged from 1.96 to 43.20â¯mgâ¯g(-1), with a mean of 13.75â¯mgâ¯g(-1). Relatively high 1,2,6-TGGP contents (>30â¯mgâ¯g(-1)) in two tea cultivars indicate that the beneficial effects of 1,2,6-TGGP can be obtained by consuming these teas. The chemotaxonomy analysis showed a biosynthetic relation between 1,2,6-TGGP and gallic acid. Further analysis showed that the 1,2,6-TGGP contents significantly decreased with the plucking times irrespective of the cultivars. Moreover, a positive and significant correlation was also observed between 1,2,6-TGGP and gallic acid. The identification of tea cultivars that are rich in 1,2,6-TGGP was first reported and the obtained results should boost their potential use in food and medicine. | Camellia sinensis |
INTRODUCTION: S. aureus is a Gram positive bacterium which is responsible for a wide range of infections. This pathogen has also the ability to adhere to biotic or abiotic surface such as central venous catheter (CVC) and to produce a biofilm. The aim of this study was to evaluate the effect of hexadecyltrimethyl ammonium bromide (HTAB) and Hexadecylbetainate chloride (HBC) on Staphylococcus aureus adherence to the catheter tubing and on bacteria growth. METHODS: Broth microdilution method was used to determine the Minimal Inhibitory Concentration (MIC). The detection of slime production was done by Congo Red Agar method, and the adherence of bacteria to the catheter tubing was evaluated by the enumeration of bacteria on plate counts. RESULTS: The results of this study showed that the MICs of HTAB were ranged from 0.125 to 0.5 microg/mL, and those of HBC fluctuated between 2 to 8 microg/mL. HTAB and HBC inhibited bacteria adhesion on the surface of the catheter tubing. CONCLUSION: This study showed that HTAB and HBC can prevent the adherence of S. aureus strains to the surface of catheter tubing, suggesting that they could be used to prevent the risk of catheter related bloodstream infections. | Trimethyl Ammonium Compounds |
BACKGROUND: A 45-year old woman of Cambodian ethnic background presented with fatal respiratory failure due to a severe diaphragmatic dysfunction. Two years before, she had developed early onset of urinary symptoms. METHODS AND RESULTS: Neuroimaging showed atrophy of the spine and medulla as well as a leukodystrophy affecting both supra- and infra-tentorial regions. At autopsy, polyglucosan bodies (PB) were seen in several peripheral tissues, including the diaphragm, and nervous tissues such as peripheral nerves, cerebral white matter, basal ganglia, hippocampus, brainstem and cerebellum. Immunohistochemistry and electron microscopy of the brain revealed an exclusive astrocytic localization of the PB. The diagnosis of adult polyglucosan body disease (APBD) was confirmed by enzymatic and molecular studies. CONCLUSION: Storage of abnormal glycogen in astrocytes is sufficient to cause the leukodystrophy of APBD. Since brain glycogen is almost exclusively metabolized in astrocytes, this observation sheds light on the pathophysiology of APBD. In addition, this is the first report of an APBD patient presenting with a subacute diaphragmatic failure. | Glycogen Storage Disease |
BACKGROUND AND AIMS: The actual number of domestications of a crop is one of the key questions in domestication studies. Answers to this question have generally been based on relationships between wild progenitors and domesticated descendants determined with anonymous molecular markers. In this study, this question was investigated by determining the number of instances a domestication phenotype had been selected in a crop species. One of the traits that appeared during domestication of common bean (Phaseolus vulgaris) is determinacy, in which stems end with a terminal inflorescence. It has been shown earlier that a homologue of the arabidopsis TFL1 gene - PvTFL1y - controls determinacy in a naturally occurring variation of common bean. METHODS: Sequence variation was analysed for PvTFL1y in a sample of 46 wild and domesticated accessions that included determinate and indeterminate accessions. KEY RESULTS: Indeterminate types - wild and domesticated - showed only synonymous nucleotide substitutions. Determinate types - observed only among domesticated accessions - showed, in addition to synonymous substitutions, non-synonymous substitutions, indels, a putative intron-splicing failure, a retrotransposon insertion and a deletion of the entire locus. The retrotransposon insertion was observed in 70 % of determinate cultivars, in the Americas and elsewhere. Other determinate mutants had a more restricted distribution in the Americas only, either in the Andean or in the Mesoamerican gene pool of common bean. CONCLUSIONS: Although each of the determinacy haplotypes probably does not represent distinct domestication events, they are consistent with the multiple (seven) domestication pattern in the genus Phaseolus. The predominance of determinacy in the Andean gene pool may reflect domestication of common bean prior to maize introduction in the Andes. | Phaseolus |
Radial keratotomy has always produced ambivalent feelings in the Ophthalmologist. The severe complications produced by the Sato procedure has been an unforgettable episode. The work of Fyodorov and Durney (1979) and their American counterparts, Bores (1981) and Hoffer (1981) have done a great service to radial keratotomy in having it established as an acceptable procedure. The controversy really only abated with the work of the National Institute of Health Funded Prospective Evaluation of Radial Keratotomy (PERK) study which suggested that the procedure has a low initial risk and was effective in decreasing myopic correction. Over the last 3 years a series of cases where evaluated and followed up in detail in an effort to gain a perspective on the one problem which has bugged the radial keratotomy programme from the beginning-its predict-ability. | Keratotomy, Radial |
Our understanding on the functions of circadian clocks has deepened at a pace in recent years. Elucidation of the mechanisms of action might pave the way to a range of interventions of use in clinical practice in many fields of medicine. | Circadian Clocks |
BACKGROUND: Blastocystis sp. is a unicellular eukaryote that is commonly found in the human intestine. Its ability to cause disease is debated and a subject for ongoing research. In this study, faecal samples from 35 Swedish university students were examined through shotgun metagenomics before and after travel to the Indian peninsula or Central Africa. We aimed at assessing the impact of travel on Blastocystis carriage and seek associations between Blastocystis and the bacterial microbiota. RESULTS: We found a prevalence of Blastocystis of 16/35 (46%) before travel and 15/35 (43%) after travel. The two most commonly Blastocystis subtypes (STs) found were ST3 and ST4, accounting for 20 of the 31 samples positive for Blastocystis. No mixed subtype carriage was detected. All ten individuals with a typable ST before and after travel maintained their initial ST. The composition of the gut bacterial community was not significantly different between Blastocystis-carriers and non-carriers. Interestingly, the presence of Blastocystis was accompanied with higher abundances of the bacterial genera Sporolactobacillus and Candidatus Carsonella. Blastocystis carriage was positively associated with high bacterial genus richness, and negatively correlated to the Bacteroides-driven enterotype. These associations were both largely dependent on ST4 - a subtype commonly described from Europe - while the globally prevalent ST3 did not show such significant relationships. CONCLUSIONS: The high rate of Blastocystis subtype persistence found during travel indicates that long-term carriage of Blastocystis is common. The associations between Blastocystis and the bacterial microbiota found in this study could imply a link between Blastocystis and a healthy microbiota as well as with diets high in vegetables. Whether the associations between Blastocystis and the microbiota are resulting from the presence of Blastocystis, or are a prerequisite for colonization with Blastocystis, are interesting questions for further studies. | Blastocystis Infections |
Due to a number of radical changes in society, the role of parents in the upbringing of their children has been redefined. In this essay, Paul Smeyers argues that risk" thinking, and the technologization that goes with it in the context of child rearing, naturally leads to the rights discourse, but that thinking about the relation between parents and children in terms of rights confronts one with a number of insurmountable problems. The concept of the "best interests of a child" that is often invoked is, to say the least, not at all clear. Smeyers contends that while the discourse of rights is clearly important and relevant insofar as the relation between parents and the state are discussed, it impoverishes our understanding of relations of family members when used as an all-inclusive framework in that context. Therefore, he concludes that we must surpass the totalizing tendency of the transformation of the social realm into a system, of defining the relation between parents and children in technical terms, and of holding parents liable for their children's upbringing." | Child Rearing |
OBJECTIVE: To compare plasma surfactant protein-D levels in healthy smokers and Chronic obstructive pulmonary disease patients. METHODS: The comparative study was conducted at the University of Health Sciences, Lahore, Pakistan, from January to December 2015, and comprised chronic obstructive pulmonary disease patients and healthy smokers of either gender aged 40-80 years. Plasma surfactant protein-D levels of male and female subjects were estimated and compared with lung function and tobacco exposure. Blood samples were collected after complete history, physical examination and spirometry. Plasma levels were measured using enzyme-linked immunosorbent assay. Plasma cotinine levels were also measured for the determination of tobacco as well as biomass exposure along with pack years. SPSS 20 was used for data analysis.. RESULTS: Of the 84 subjects, there were 42(50%) patients and as many controls. Both groups had 21(50%) males and as many females. There was no significant difference in the plasma surfactant protein-D levels of males and females in the patient group compared to their counterparts in the control group (p>0.05). Females developed the disease at a younger age compared to males (p=0.04). There was no significant difference in terms of pack-years and cotinine levels between the groups (p>0.05) and lung function showed greater deterioration in the females compared to males with similar tobacco exposure (p<0.05).. CONCLUSIONS: The gender did not affect plasma surfactant protein-D levels. | Pipe Smoking |
Adenosine kinase (ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20) has been purified 3250-fold from Leishmania donovani promastigotes using ion-exchange, gel filtration, and affinity chromatography techniques. Both native and sodium dodecyl sulfate-gel electrophoresis of the enzyme revealed a single polypeptide of around 38,000 molecular weight. Biophysical and biochemical analyses of the enzyme reveal unique characteristics different from those of adenosine kinases from other eukaryotic sources. The isoelectric pH of the enzyme is 8.8. In native acrylamide gels the enzyme moves with an RF of about 0.62. The enzyme displays a maximum activity at pH between 7.5 and 8.5 and is dependent upon an optimum ATP/Mg2+ ratio. ATP at high concentration inhibits the reaction. Adenosine and Mg2+ are not inhibitory. EDTA completely knocks off the activity. Enzyme activity is dependent upon the presence of active thiol group(s) at or near the active center. Under a defined set of conditions the enzyme exhibited an apparent Km for adenosine and ATP of 33 and 50 microM, respectively. Of the nucleoside triphosphates tested ATP and GTP were the most effective phosphate donors. Marginal inhibition of activity was detected with other nucleosides as competitors. However, adenosine analogs, such as 7-deaza-adenosine (tubercidin) and 6-methylmercaptopurine riboside at very low concentrations, were found to be excellent inhibitors and substrates as well. S-Adenosylhomocysteine does not inhibit the reaction even at very high concentration. | Adenosine Kinase |
The present investigation was designed to 1) determine if atrial natriuretic-like peptides are present throughout the plant kingdom and 2) to determine if these peptides increase the flow of solute and/or water upward to leaves and flowers of plants. The 126-amino acid prohormone of atrial natriuretic factor (proANF)-(1-30), proANF-(31-67), and atrial natriuretic factor (ANF)-like peptides were present in the roots, stems, leaves, and flower petals of the more highly developed plants (Tracheophyta), with their highest concentrations being: Florida beauty > buddhist pine > Boston fern > rose = geranium = resurrection plant or club moss > Moses-in-the-cradle > Florida coontie. These peptides were also present in Bryophata (plants without vascular tissue or roots) and even in Euglena, flagellated chlorophyll-containing plants without leaves, stems, or roots. proANF-(1-30), proANF-(31-67), and proANF-(79-98) but not ANF (each at < 5.9 pg/ml) significantly increased (P < 0.001) the flow of colored water up stems, coloring their flowers 15-35 min earlier than the other one-half of the same flowers without exogenous peptide addition. These same peptides increased the rate of transpiration (i.e., loss of water from the leaves) and the absorption of solutions. High-performance gel permeation chromatography revealed that proANF-(1-30), proANF-(31-67), and ANF extracted from plants are very similar to their pure synthetic human sequences, with elution profiles and molecular weights of the plant extracts duplicating those of the pure synthetic peptides. | Natriuretic Peptides |
Specific binding of ATP to bovine serum albumin (BSA) is demonstrated employing ATP derivatives spin-labeled at either N6 or C8 of adenine ring or at the ribose moiety. Based on a 1:1 stoichiometry binding constants are in the 50-100 microM range. Binding is largely competitive with ATP or stearic acid. A small fraction of the labeled nucleotides could not be liberated by these ligands. Binding of AMP is in the millimolar range, only. | Serum Albumin, Bovine |
BACKGROUND: The Armed Forces operate in a particularly arduous physical and psychological environment. The occupational health (OH) of all personnel is of paramount importance to sustain the service's fighting ability. AIMS: Firstly, to bring readers up to date with the current organization and delivery of OH to uniformed personnel in the Armed Forces. Secondly, to review the research that has led to an improvement in OH services and the ways in which the Armed Forces are responding to the various challenges. METHODS: A description of the type and delivery of OH to the Armed Forces is followed by a review of the relevant contemporaneous literature from both open publications and research dissertations. RESULTS: Although there are some similarities with civilian OH, the principal requirement to prepare and sustain service personnel for operations on land, sea and air adds considerable complexity to the task. Research undertaken by Armed Forces OH professionals has added to the evidence base and enabled attrition in all aspects of the Armed Forces to be reduced. CONCLUSIONS: To meet the challenges of the 21st century, Armed Forces OH practitioners must continue to provide the best evidence-based advice to enhance force preparation and sustainment. All consultations in the Armed Forces involve an OH consideration from the simplest consultations through to the input from specialist OH practitioners. While the assessment of fitness to work in home bases and on deployed operations remains the primary output of OH, the provision of support to command policy, procurement and research are also key to the ability to operate worldwide. | Occupational Medicine |
A new species of Creagrutus is described from the Amazonian Piedmont, Colombia. The new species can be distinguished from congeners by presenting the following unique combination of characters: a dark mid-lateral stripe starting at anteriormost scale of lateral line, a vertically elongated humeral blotch, absence of dark blotches on dorsal fin and at base of middle caudal-fin rays, a triangular dentigerous surface of the premaxilla, 5-6 dentary teeth, and 11-12 predorsal scales. Comparisons with congeners distributed in the piedmont region of Rio Caqueta basin are presented and its relationships among species of Creagrutus is inferred from the available phylogenetic framework. | Characidae |
STUDY QUESTION: Do the attachment-related dimensions Anxiety and Avoidance and perceived partner and social support in recipients and donors influence disclosure to others about their involvement in donor-assisted conception (DAC)? SUMMARY ANSWER: A higher global score on attachment Avoidance was associated with greater non-disclosure about involvement in DAC by participants to relationship-specific others. WHAT IS KNOWN ALREADY: Within the context of DAC, the topic of disclosure has been investigated in terms of the 'if', 'when', and the 'how' to disclose about circumstances of conception. Less focus, however, has been directed to investigating psychological theoretical frameworks that influence disclosure decisions to others, i.e. to whom information is disclosed and to what extent details are transparently revealed about the donor programme. STUDY DESIGN, SIZE, DURATION: The study was of a cross-sectional design and utilized a sample of 301 participants who were, or had been, involved in DAC, and were recruited across states of Australia. An online self-report questionnaire was completed between June 2014 and June 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: English speaking participants consisting of 209 female recipients and 92 donors (36 sperm; 48 egg; 8 embryo donors). Of the recipients, 104 had successfully conceived children via donated gametes (68 sperm, 23 eggs, 6 embryos, and 7 recipients where both gametes were donated from 2 donors to create the embryo). Participants anonymously completed an online questionnaire consisting of five sections: Demographics, Donor Conception and Disclosure Practices, the Experiences in Close Relationships-Relationships Structure, the Quality of Relationship Inventory, and the Multidimensional Scale of Perceived Social Support. Pearson correlations, independent samples t-tests, Chi-square, and ANOVA were used to explore the association between attachment Anxiety and Avoidance scores and disclosure about involvement in a DAC programme to significant others (i.e. parents, siblings, in-laws, and friends). MAIN RESULTS AND THE ROLE OF CHANCE: Compared to published community cohort data, participants reported lower global scores on attachment Anxiety and Avoidance and high levels of romantic partner and social network support, suggestive of secure relationships in the overall study sample. A higher score on attachment Avoidance was associated with less disclosure to significant others in their social network (i.e. parents, siblings, in-laws, and close friends), even in the presence of strong partner support (partial r = -0.248, P = 0.005). Higher scores on attachment Avoidance were inversely associated with level of perceived partner and social network support (all P < 0.05). Irrespective of attachment scores, more than 90% of all participants agreed that a child born of DAC should be told about mode of conception. LIMITATIONS, REASONS FOR CAUTION: This study utilized a cross-sectional design precluding causal inferences between dimensions of insecure attachment and disclosure practices. Participants were required to self-report on the quality of their relationships with the potential for social desirability respondent bias. The study's self-selecting sample may limit generalization to participants who were dis-inclined to participate. Specifically, respondents who have an Avoidant attachment style, may have elected not to participate in the study. WIDER IMPLICATIONS OF THE FINDINGS: Given the increased use of biotechnology and digital facial recognition enabling self-discovery of the donor and the donor's extended family, non-disclosure about involvement in DAC may have consequences. An 'Avoidant' attachment style is important to assess as a potential risk factor for non-disclosure about involvement in DAC across different relational contexts (e.g. close family members and friends). Fertility counsellors should consider introducing a measure of attachment screening as a pre-emptive psychoeducational strategy during donor implications counselling. This information could be used to offer patients insight into concerns they have about DAC disclosures to key important relationships, providing a target of clinical intervention. STUDY FUNDING/COMPETING INTEREST(S): No external funds were sought for this work. None of the authors have any competing interests to declare. TRIAL REGISTRATION NUMBER: N/A. | Donor Conception |
OBJECTIVE AND DESIGN: Postoperative cognitive dysfunction (POCD) is a common complication following surgery among elderly patients. Emerging evidence demonstrates that neuroinflammation plays a pivotal role in the pathogenesis of POCD. This study tested the hypothesis that fluoxetine can protect against POCD by suppressing hippocampal neuroinflammation through attenuating TLR4/MyD88/NF-kappaB signaling pathway activation. SUBJECTS: Aged C57BL/6 J male mice (18 months old) were studied. TREATMENT: Aged mice were intraperitoneally injected with fluoxetine (10 mg/kg) or saline for seven days before splenectomy. In addition, aged mice received an intracerebroventricular injection of a TLR4 agonist or saline seven days before splenectomy in the rescue experiment. METHODS: On postoperative days 1, 3, and 7, we assessed hippocampus-dependent memory, microglial activation status, proinflammatory cytokine levels, protein levels related to the TLR4/MyD88/NF-kappaB signaling pathway, and hippocampal neural apoptosis in our aged mouse model. RESULTS: Splenectomy induced a decline in spatial cognition, paralleled by parameters indicating exacerbation of hippocampal neuroinflammation. Fluoxetine pretreatment partially restored the deteriorated cognitive function, downregulated proinflammatory cytokine levels, restrained microglial activation, alleviated neural apoptosis, and suppressed the increase in TLR4, MyD88, and p-NF-kappaB p65 in microglia. Intracerebroventricular injection of LPS (1 mug, 0.5 mug/muL) before surgery weakened the effect of fluoxetine. CONCLUSION: Fluoxetine pretreatment suppressed hippocampal neuroinflammation and mitigated POCD by inhibiting microglial TLR4/MyD88/NF-kappaB pathway activation in aged mice." | Postoperative Cognitive Complications |
'Power' and 'aggression' are two constructs that seem like a natural fit. After all, why should people in power not deploy aggression to get their way? Yet, when looking at empirical studies, the relationship between power and aggression is fickle at best. In an effort to integrate the literature, the present narrative review draws on a neuro-biological model of aggression as a framework, which distinguishes between three motivational mechanisms: offence, defence, and marking/display. High (versus low) power likely facilitates offensive aggression and agonistic marking/display. However, high (versus low) power often coincides with elevated status, which counters some of the detrimental effects of power. Meanwhile, defensive aggression is relatively underresearched, but may be a more frequent occurrence amongst lower power individuals and groups. | Power, Psychological |
INTRODUCTION: Several methods for measuring fibrinolytic capacity in plasma have been developed yielding frequently inconsistent results. We investigated which factors determine fibrinolytic capacity in three plasma-based assays. MATERIAL AND METHODS: In 80 apparently healthy controls (aged 43 +/- 10 years, 50 women [62.5%]) we evaluated fibrinolysis using three assays: (1) by Pieters et al. (CLT2018), (2) by Lisman et al. (CLT), and (3) by Carter et al. (Lys50). Coagulation factors and fibrinolytic proteins, including histidine-rich glycoprotein (HRG) and gamma'-fibrinogen, were determined. Regression models were performed to identify determinants of lysis times. RESULTS: Positive correlations were observed between CLT2018 and both CLT (r = 0.73) and Lys50 (r = 0.61), as well as between CLT and Lys50 (r = 0.46, all p < 0.001). The main determinants of both CLT2018 and CLT were plasminogen activator inhibitor-1 (PAI-1), followed by thrombin-activatable fibrinolysis inhibitor (TAFI) and alpha(2)-antiplasmin. Histidine-rich glycoprotein was a predictor of the longest-normal CLT2018 alone (OR 1.04, 95% CI 1.02-1.06). alpha(2)-Antiplasmin and fibrinogen levels, followed by PAI-1 and TAFI determined Lys50. After adjustment for age, sex, and body mass index, C-reactive protein (CRP) was an independent predictor of the top quartiles of the three lysis times. CONCLUSIONS: We showed that apart from PAI-1, TAFI, and alpha(2)-antiplasmin, several other factors, in particular CRP, can affect the results of global fibrinolysis tests used in research. Our findings may help understand why the choice of a specific fibrinolysis assay can affect the presence and/or magnitude of intergroup differences in fibrinolytic capacity in a given disease state. | Fibrin Clot Lysis Time |
OBJECTIVE: Transthoracic impedance (TTI) is a factor determining the magnitude of the transmyocardial current during external defibrillation. Minimising TTI increases the chances of successful defibrillation. Most external defibrillation paddles are rectangular in shape and can, therefore, be placed in a transverse or longitudinal orientation. The apical paddle is often placed in a transverse orientation. This may theoretically result in a higher TTI than a longitudinal orientation because of poorer contact at the lateral paddle edges. We compared TTI with the apical paddle in both a transverse and longitudinal orientation. MATERIALS AND METHODS: Twenty sequential anaesthetised patients were studied. A pair of defibrillator paddles were instrumented to measure paddle force. TTI was recorded pre-operatively at end-expiration with the apical paddle in both longitudinal and transverse orientations. The sternal paddle was placed in a longitudinal orientation for all measurements. RESULTS: TTI decreased in both transverse and longitudinal orientations as paddle force increased. Transverse paddle orientation resulted in a significantly (P<0.01) higher TTI than longitudinal orientation at all paddle forces below 12 kg force. CONCLUSION: The longitudinal orientation of a rectangular defibrillation paddle provides a lower TTI than orientation horizontally. | Electric Countershock |
OBJECTIVE: To describe an endoscopic perspective of the surgical anatomy of the trigeminal nerve. METHODS: Nine adult cadaveric heads were dissected endoscopically. RESULTS: Opening the pterygopalatine fossa is important because many key anatomical structures (V2, pterygopalatine ganglion, vidian nerve) can be identified and traced to other areas of the trigeminal nerve. From the pterygopalatine ganglion, the maxillary nerve and vidian nerve can be identified, and they can be traced to the gasserian ganglion and internal carotid artery. An anteromedial maxillectomy increases the angle of approach from the contralateral nares due to an increase in diameter of the piriform aperture, and provides excellent access to the mandibular nerve, the petrous carotid, and the cochlea. CONCLUSIONS: Identification of key anatomical structures in the pterygopalatine fossa can be used to identify other areas of the trigeminal nerve, and an anteromedial maxillectomy is necessary to expose the ipsilateral mandibular nerve and contralateral cranial level of the trigeminal nerve. | Pterygopalatine Fossa |
Microneurosurgery requires dexterity, precision and delicate force application in order to be carried out safely and effectively. Neurosurgeons must apply sufficient force in order to carry out microsurgical procedures effectively but not excessive force such that iatrogenic injury occurs. This paper presents a smart hand-held microsurgical instrument that indicates to the surgeon when a force-threshold has been exceeded by providing vibrotactile feedback. Many existing haptic-feedback systems, particularly master-slave robotic platforms, are large, highly complex, and costly. By comparison, the proposed device is compact, fail-safe and low cost. Two psychophysical user studies were carried out to assess the proposed vibrotactile force-threshold feedback system. A cadaveric pilot study was carried out to evaluate the device in a microdissection task. In all the studies performed, the haptic dissector device has shown to be effective in providing real-time feedback in terms of force application during microsurgical tasks. | Microdissection |
INTRODUCTION: The paediatric radiation dose has never been studied in Sri Lanka, nor has a national diagnostic reference level (NDRL) established. Therefore, the primary aim of this study was to propose diagnostic reference levels (DRL) and achievable dose (AD) values for paediatric CT examinations based on size. METHODS: A total of 658 paediatric (0-15 years) non-contrast-enhanced (NC) studies of head, chest and abdomen regions performed during six months in two dedicated paediatric hospitals (out of the three such institutions in the country) were included. For head examinations, the dose indexes were analysed based on age, while for body examinations, both age and effective diameter (D(eff)) were used. The median and the third quartile of the pooled dose distribution were given as AD and NDRL, respectively. RESULTS: The AD ranges for the head, chest and abdomen regions based on CTDI(vol) were 45.8-57.2 mGy, 2.9-10.0 mGy and 3.8-10.3 mGy. The corresponding NDRL ranges were 45.8-95.8 mGy, 3.5-14.1 mGy and 4.5-11.9 mGy. The AD ranges based on SSDE(deff) and d(eff) were 3.5-9.6 mGy and 4.1-10.3 mGy in chest and abdomen regions. The corresponding NDRL were 4.5-14.1 mGy and 6.1-10.6 mGy. CONCLUSION: Other institutions can use the present study DRLs as a reference dose for paediatric CT. The AD values can be used as a baseline for target dose optimisations, reducing doses up to 90%. | Radiation Dosage |
Cells of several strains of Streptococcus gordonii attached in much higher numbers to experimental pellicles formed from samples of submandibular or parotid saliva on hydroxyapatite (HA) beads than to buffer controls. The nature of the salivary components responsible were investigated by preparing experimental pellicles from chromatographic fractions of submandibular saliva obtained from Trisacryl GF 2000M columns. Adhesion of S. gordonii Blackburn was promoted by two groups of fractions. The adhesion-promoting activity in the first group of fractions was associated with the family of acidic proline-rich proteins (PRPs), while that of the second group is as yet unidentified. Experimental pellicles prepared by treating HA with 2 micrograms of pure 150-amino-acid-residue PRPs (PRP-1, PRP-2, and PIF-s) promoted adhesion of S. gordonii Blackburn cells to an extent comparable to that obtained with unfractionated saliva. However, pellicles prepared from a 106-residue PRP (PRP-3) were significantly less effective, and those prepared from the amino-terminal tryptic peptide (residues 1 to 30) of the PRP and the salivary phosphoprotein statherin were completely ineffective in promoting adhesion. Although adhesion of several strains of S. gordonii was promoted by adsorbed PRP-1, the adhesion of several strains of Streptococcus sanguis or Streptococcus oralis was either not affected or only weakly enhanced by this protein. S. gordonii cells bound avidly to PRPs adsorbed onto HA beads, but the streptococci did not appear to bind PRPs in solution, since concentrations of PRP as high as 200 micrograms/ml did not inhibit binding of bacterial cells to pellicles prepared from pure PRP. S. gordonii cells also attached well to PRP or a synthetic decapeptide representing residues 142 to 150 of the PRP when the peptide was linked to agarose beads. Studies with a series of synthetic decapeptides indicated that the minimal segment of PRP which promoted high levels of S. gordonii adhesion was the carboxy-terminal dipeptide Pro-Gln (residues 149 and 150)." | Salivary Proline-Rich Proteins |
BACKGROUND: The ADVIA 120 is an automated laser cell counter widely used in veterinary medicine. Although specific software for equine samples is available and validated, only a few reports have been published comparing the ADVIA 120 with other methods for equine hemogram evaluation. OBJECTIVES: The purpose of this study was to compare the hematologic values and reference intervals obtained on the ADVIA 120 with those obtained on an impedance cell counter and manual differential counts in healthy horses. METHODS: EDTA-anticoagulated blood samples were obtained from 114 clinically healthy horses of various breeds, both sexes, and 2-6 years of age. Samples were stored for up to 12 hours at 4 degrees C and then analyzed on the ADVIA 120 and the Hemat 8. A 100-cell to 200-cell differential leukocyte count was performed by 3 independent observers on May-Grunwald-Giemsa-stained smears. Intra-assay precision of the ADVIA 120 was determined by analyzing 5 replicates each of 10 of the blood samples. RESULTS: Results from the ADVIA were significantly higher than those from the impedance counter for RBC count, total WBC count, hemoglobin concentration, red cell distribution width, MCH, and MCHC, and significantly lower for HCT and platelet count. Significantly higher neutrophil and basophil counts and significantly lower lymphocyte counts were obtained with the ADVIA 120 compared with manual counts. Based on Passing-Bablok regression analysis, RBC and platelet counts were in good agreement between the 2 analyzers; a constant and proportional bias was present for other values. Coefficients of variation for erythrocyte parameters on the ADVIA were <1%, but were higher for platelet (6%), total WBC (2%), differential WBC (4%-30%), and reticulocyte (75%) counts. CONCLUSIONS: Results obtained with equine samples on the ADVIA 120 were comparable with those obtained on an impedance counter; reference intervals differed statistically but overlapped. The ADVIA had poor precision for reticulocyte and differential leukocyte counts such that the latter should always be verified on smears. | Blood Cell Count |
In order to determine the effect of different image compounding functions on perceived image quality, 84 pairs of ultrasound images were collected, mixed, and reviewed by four independent observers who were asked to identify the highest quality image of each pair. Each image in a pair was made using the same orientation, transducer, frequency, and gain settings but different compounding settings. Outcomes were analyzed using logistic regression. Observers judged compound images to be better quality than noncompound images in 69% cases, the same quality in 24%, and poorer quality in 7%. Overall, compound images were considered significantly better quality than noncompound images (P < 0.001). Compound images were more likely to be considered better quality than the corresponding noncompound images when combined transmit/receive spatial compounding was used rather than receive-only spatial compounding or transmit compounding, and when the vector transducer or the curvilinear transducer were used rather than the linear transducer. Observers considered improved border definition and increased signal to noise ratio to be the properties that accounted most often for higher quality of compound images compared with noncompound images. | Ultrasonography |
OBJECTIVES: Use of nonbenzodiazepine sedative hypnotics, especially zolpidem, has grown substantially, raising concerns about safety. Here, we evaluated prescribing patterns of zolpidem in the Veterans Health Administration. STUDY DESIGN: A cross-sectional study of veterans receiving zolpidem in the outpatient setting from October 1, 2011, to September 30, 2016. METHODS: The study population consisted of 500,332 zolpidem users (58,598 women and 441,734 men) and a random 10% sample (n = 631,449) of nonusers. We examined 2 outcomes related to inappropriate prescribing: high-dose zolpidem prescribing and overlap with benzodiazepines. We generated interrupted time series and logistic regression models to analyze these outcomes in men and women separately. RESULTS: In 2016, 29.7% of female veterans received an inappropriately high guideline-discordant dosage compared with 0.1% of male veterans (P <.001 for all reported comparisons). Furthermore, more women than men had overlapping benzodiazepine and zolpidem prescriptions (18.8% vs 14.3%). In fully adjusted models, inappropriately high doses were more commonly received by younger women (adjusted odds ratios [AORs]: 2.75 for 21-39 years and 2.97 for 40-49 years compared with >/=80 years) and women with substance use disorder (AOR, 1.48). In the second inappropriateness outcome models, women with anxiety (AOR, 2.28) or schizophrenia (AOR, 2.05) and men with cancer (AOR, 1.42), anxiety (AOR, 2.66), or schizophrenia (AOR, 2.46) were more likely to receive an overlapping prescription of zolpidem and benzodiazepines. CONCLUSIONS: We found evidence of inappropriate zolpidem prescribing among veterans, particularly women. Greater understanding of the drivers of this inappropriate prescribing is necessary to develop interventions to promote safer, more guideline-concordant prescribing. | Zolpidem |
SIGNIFICANCE: For optical methods to accurately assess hemoglobin oxygen saturation in vivo, an independently verifiable tissue-like standard is required for validation. For this purpose, we propose three hemoglobin preparations and evaluate methods to characterize them. AIM: To spectrally characterize three different hemoglobin preparations using multiple spectroscopic methods and to compare their absorption spectra to commonly used reference spectra. APPROACH: Absorption spectra of three hemoglobin preparations in solution were characterized using spectroscopic collimated transmission: whole blood, lysed blood, and ferrous-stabilized hemoglobin. Tissue-mimicking phantoms composed of Intralipid, and the hemoglobin solutions were characterized using spatial frequency-domain spectroscopy (SFDS) and enhanced perfusion and oxygen saturation (EPOS) techniques while using yeast to deplete oxygen. RESULTS: All hemoglobin preparations exhibited similar absorption spectra when accounting for methemoglobin and scattering in their oxyhemoglobin and deoxyhemoglobin forms, respectively. However, systematic differences were observed in the fitting depending on the reference spectra used. For the tissue-mimicking phantoms, SFDS measurements at the surface of the phantom were affected by oxygen diffusion at the interface with air, associated with higher values than for the EPOS system. CONCLUSIONS: We show the validity of different blood phantoms and what considerations need to be addressed in each case to utilize them equivalently. | Hemeproteins |
Fingerprints, which are associated with touch samples, typically contain a limited amount of DNA. The amount of available DNA can be further reduced when the same touch samples undergo fingerprint processing [1]. The fingerprint development process consists of high-powered lighting (inherent luminescence and UV light) and chemical compounds (ninhydrin, black powder, cyanoacrylate, and rhodamine 6 G) which could reduce DNA quality and quantity. Therefore, forensic scientists often must select one type of analysis over the other due to the destructive nature of processing. DNA and latent fingerprinting are both useful sources for identification, although both can produce partial results. A partial DNA profile may only contain a few alleles, limiting the ability to identify a potential suspect to perform comparisons. A partial fingerprint generally means that only a very small part of the fingerprint is present, which makes comparisons difficult. Because partial results are common, combining data from both fingerprinting and DNA analysis would increase the confidence of an identification of a person. Significant research has been performed to determine if a DNA profile can be obtained from latent processed fingerprints; however, there has yet to be research done in a standardized manner. In this study, we used standardized mock fingerprints" in order to reduce fingerprint DNA variability and specifically focused on DNA quantitation after each step in the fingerprinting process. Results suggest that latent print processing techniques used on non-porous surfaces (plastic, duct-tape, metal, and rubber) do not affect DNA quantity or quality. In contrast, ninhydrin, a chemical used for processing fingerprints present on porous surfaces (wood and paper), significantly reduced DNA recovery. Together these results suggest that DNA can still be performed on latent print processed items, unless ninhydrin has been used." | Ninhydrin |
The anterior palatal area may be related with the flexural rigidity and bending strength of the upper complete dentures. Therefore, the deformation of this area should be measured widely and continuously when new materials were applied to the dentures. The influence of the photoelastic coating on the mechanical properties of the upper complete dentures was investigated, prior to the measurement of surface strains on the denture bases by the photoelastic coatings. In this experiment, the uniform-moment bending method was employed simulating the occlusal situation. The flexural rigidity of the denture bases depended on the palatal materials in spite of the presence of the coating. The strains concentrated on the anterior palatal area were slightly decreased when the coating was bonded to the polished surface of the palate. The reinforcing effect was significant when the resin dentures of low elastic modulus were coated. The photoelastic-coating method was suitable for the qualitative analysis of the strain distribution of the denture base and selecting the test points to make strain measurement accurate. | Denture, Complete, Upper |
3-oxohexadecanoyl-CoA was synthesized for the study of D-bifunctional protein (EC 4. 2. 1. 107, EC 4. 2. 1. 119, EC 1. 1. 1. n12) and L-bifunctional protein (EC 4. 2. 1. 17, EC 5. 3. 3. 8, EC 1. 1. 1. 35). First, tetradecanal was subjected to the Reformatsky reaction with ethyl bromoacetate, and the product was then converted into ethyl 3-oxohexadecanoate. After acetalization of the 3-oxo ester with ethylene glycol, 3,3-ethlenedioxyhexadecanoic acid was obtained by alkaline hydrolysis. The acid was condensed with coenzyme A (CoA) by the mixed anhydride method, and the resulting CoA ester was deprotected with 4 M HCl to obtain 3-oxohexadecanoyl-CoA. In addition, the behavior of the CoA ester under several conditions of high-performance liquid chromatography (HPLC) was also investigated. We established separation detection of (R)-3-hydroxyhexadecanoyl-CoA, (S)-3-hydroxyhexadecaboyl-CoA, 3-oxohexadecanoyl-CoA, and trans-2-hexadecenoyl-CoA." | Peroxisomal Multifunctional Protein-2 |
BACKGROUND: The threat of 2009 pandemic influenza A (H1N1) is still causing widespread public concern. A comprehensive understanding of the epidemiology of 1918 pandemic influenza commonly referred to as the Spanish flu may be helpful in offering insight into control strategies for the new pandemic. OBJECTIVE: We explore how the preparedness for a pandemic at the community and individual level impacts the spread of the virus by comparing the transmissibility of the 1918 Spanish flu in two Canadian cities: Montreal and Winnipeg, bearing in mind that each pandemic is unique and the current one may not follow the pattern of the 1918 outbreak. METHODS: The historical epidemiological data obtained for Montreal and Winnipeg in Canada is analyzed to estimate the basic reproduction number which is the most important summary measure of transmission potential of the pandemic. RESULTS: The transmissibility of the 1918 pandemic influenza virus in Winnipeg in the fall of 1918 was found to be much lower than in Montreal based on the estimated reproduction number obtained assuming different serial intervals which are the time between onsets of symptoms in an index case and a secondary case. CONCLUSION: The early preparedness and public health control measures could suggest an explanation for the fact that the number of secondary cases generated by a primary case was significantly reduced in Winnipeg comparing to it in Montreal." | Disease Transmission, Infectious |
AIMS: To determine the ability of a novel Bacillus subtilis AMR isolated from poultry waste to hydrolyse human hair producing peptidases including keratinases and hair keratin peptides. METHODS AND RESULTS: The Bacillus subtilis AMR was identified using biochemical tests and by analysis of 16S rDNA sequence. The isolate was grown in medium containing human hair as the sole source of carbon and nitrogen. The supplementation of hair medium (HM) with 0.01% yeast extract increased the keratinolytic activity 4.2-fold. B. subtilis AMR presented high keratinase production on the 8th day of fermentation in hair medium (HM) supplemented with 0.01% yeast extract (HMY) at pH 8.0. Keratinase yield was not correlated with increase in biomass. Zymography showed keratin-degrading peptidases migrating at c. 54, 80 and 100 kDa and gelatin-degrading bands at c. 80, 70 63, 54 32 and 15 kDa. Keratinases were optimally active at 50 degrees C and pH 9.0 and was fully inhibited by the serine proteinase inhibitor (PMSF). Scanning electron microscopy showed complete degradation of the hair cuticle after exposure to B. subtilis AMR grown in HMY. MALDI-TOF analysis of culture supernatant containing peptides produced during enzymatic hydrolysis of hair by B. subtilis AMR revealed fragments in a range of 800-2600 Da. CONCLUSIONS: This study showed that B. subtilis AMR was able to hydrolyse human hair producing serine peptidases with keratinase and gelatinase activity as well as hair keratin peptides. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report describing the production and partial characterization of keratinases by a B. subtilis strain grown in a medium containing human hair. These data suggest that peptides obtained from enzymatic hair hydrolysis may be useful for future applications on pharmaceutical and cosmetic formulations. | Keratins, Hair-Specific |
Polypharmacology has been increasingly advocated for the therapeutic intervention in complex pathological conditions, exemplified by cancer. Although kinase inhibitors (KIs) have revolutionized the treatment for certain types of malignancies, some major medical needs remain unmet due to the relentless advance of drug resistance and insufficient efficacy of mono-target KIs. Hence, multiple targets, multi-dimensional activities" represents an emerging paradigm for innovative anti-cancer drug discovery. Over recent years, considerable leaps have been made in pursuit of kinase-centric polypharmacological anti-cancer therapeutics, providing avenues to tackling the limitation of mono-target KIs. In the review, we summarize the clinically important mechanisms inducing KI resistance and depict a landscape of recent medicinal chemistry efforts on exploring kinase-centric polypharmacological anti-cancer agents that targeting multiple cancer-related processes. In parallel, some inevitable challenges are emphasized for the sake of more accurate and efficient drug discovery in the field." | Protein Kinase Inhibitors |
Sebaceous neoplasia comprises a spectrum ranging from benign to malignant. Proper histological identification is important for treatment, prognosis and potential association with the Muir-Torre syndrome (MTS). Our increased understanding of the significance and pathogenesis of these tumours has led to improved risk stratification, screening recommendations, and treatment of patients with an initial presentation of a sebaceous tumour. This review focuses on the diagnostic and histological features of sebaceous lesions, the MTS, and recent insights into the molecular pathogenesis of sebaceous tumours. | Muir-Torre Syndrome |
Acute lethal concentration estimates (72-hr LC50) and population growth rates (7-day instantaneous rate of increase) of two mite species, an herbivore, the two-spotted spider mite Tetranychus urticae Koch, and the generalist predator mite Iphiseius degenerans Berlese, were developed after exposure to two pesticides, dicofol and Neemix. For each pesticide, LC50 estimates for both species were similar, yet the two species exhibited completely different susceptibility when population growth rate was the endpoint evaluated; I. degenerans was much more susceptible than T. urticae to either pesticide. For example, populations of I. degenerans became extinct after exposure to 250-ppm azadirachtin, the active ingredient in Neemix, while T. urticae populations became extinct after exposure to 1000 ppm. A similar relationship was found for dicofol. The no observable effect concentration (NOEC) for population growth rates after Neemix exposure was 4 ppm for I. degenerans and 125 ppm for T. urticae. These NOEC values were equivalent to the acute LC2 for the immature stage of I. degenerans and the acute LC65 for the immature stage of T. urticae. Consequently, populations of T. urticae were able to compensate for high losses of individuals while I. degenerans populations could not compensate for losses. An analysis of reproduction data indicated that unexposed T. urticae produced four to five times more offspring than I. degenerans. This in itself was important because it indicated that I. degenerans was intrinsically more susceptible than T. urticae because similar effects on reproduction would be more devastating to the species with a lower reproductive rate. Results indicate that a species' reproductive potential can greatly influence its susceptibility to toxicants. | Dicofol |
PURPOSE: Hepatic radioembolization is an effective minimally invasive treatment for primary and metastatic liver cancers. Yttrium-90 [90Y]-labelled resin or glass beads are typically used as the radioembolic agent for this treatment; however, these are not readily available in many countries. In this study, novel samarium-153 oxide-loaded polystyrene ([153Sm]Sm2O3-PS) microspheres were developed as a potential alternative to 90Y microspheres for hepatic radioembolization. METHODS: The [152Sm]Sm2O3-PS microspheres were synthesized using solid-in-oil-in-water solvent evaporation. The microspheres underwent neutron activation using a 1 MW open-pool research reactor to produce radioactive [153Sm]Sm2O3-PS microspheres via 152Sm(n,gamma)153Sm reaction. Physicochemical characterization, gamma spectroscopy and in-vitro radionuclide retention efficiency were carried out to evaluate the properties and stability of the microspheres before and after neutron activation. RESULTS: The [153Sm]Sm2O3-PS microspheres achieved specific activity of 5.04 +/- 0.52 GBq.g-1 after a 6 h neutron activation. Scanning electron microscopy and particle size analysis showed that the microspheres remained spherical with an average diameter of ~33 mum before and after neutron activation. No long half-life radionuclide and elemental impurities were found in the samples. The radionuclide retention efficiencies of the [153Sm]Sm2O3-PS microspheres at 550 h were 99.64 +/- 0.07 and 98.76 +/- 1.10% when tested in saline solution and human blood plasma, respectively. CONCLUSIONS: A neutron-activated [153Sm]Sm2O3-PS microsphere formulation was successfully developed for potential application as a theranostic agent for liver radioembolization. The microspheres achieved suitable physical properties for radioembolization and demonstrated high radionuclide retention efficiency in saline solution and human blood plasma. | Yttrium Radioisotopes |
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