Structural characterization of the bacteriophage T7 tail machinery.
Most bacterial viruses need a specialized machinery, called "tail," to inject their genomes inside the bacterial cytoplasm without disrupting the cellular integrity. Bacteriophage T7 is a well characterized member of the Podoviridae family infecting Escherichia coli, and it has a short noncontractile tail that assembles sequentially on the viral head after DNA packaging. The T7 tail is a complex of around 2.7 MDa composed of at least four proteins as follows: the connector (gene product 8, gp8), the tail tubular proteins gp11 and gp12, and the fibers (gp17). Using cryo-electron microscopy and single particle image reconstruction techniques, we have determined the precise topology of the tail proteins by comparing the structure of the T7 tail extracted from viruses and a complex formed by recombinant gp8, gp11, and gp12 proteins. Furthermore, the order of assembly of the structural components within the complex was deduced from interaction assays with cloned and purified tail proteins. The existence of common folds among similar tail proteins allowed us to obtain pseudo-atomic threaded models of gp8 (connector) and gp11 (gatekeeper) proteins, which were docked into the corresponding cryo-EM volumes of the tail complex. This pseudo-atomic model of the connector-gatekeeper interaction revealed the existence of a common molecular architecture among viruses belonging to the three tailed bacteriophage families, strongly suggesting that a common molecular mechanism has been favored during evolution to coordinate the transition between DNA packaging and tail assembly.


A grief team within a healthcare system.
Grief is an emotion experienced by many nurses upon the death of a patient, and, far too often, the nurse may not know how to deal effectively with his or her grief. This article describes the development of a grief team within a hospital setting to assist nurses in coping with grief.


Bronchoalveolar lavage T-cell and Ia antigen quantitation by flow cytometry in acute and chronic experimental hypersensitivity pneumonitis.
Increasing evidence implicates effector T-cells in the pathogenesis of hypersensitivity pneumonitis. We utilized T-cell- and Ia-specific antibodies, flow cytometry, and computer analysis to quantitate T-cell numbers and Ia expression on lung cells of established rabbit models of acute and chronic hypersensitivity pneumonitis (HSP). We used analysis of variance (ANOVA) and Turkey's follow-up to evaluate group differences. In the acute HSP group, increased percentages of T-cells and greater Ia expression were present on bronchoalveolar lavage (BAL) cells at 24 h after inhalational allergen challenge. Increased BAL T-cell numbers were found in the chronic HSP group produced by repeated inhalation of antigen and muramyl dipeptide, compared to "desensitized" animals and control groups. Both chronic HSP and desensitized groups demonstrated increased Ia expression on BAL cells. Pathology scores for individual animals in both acute and chronic protocols correlated significantly (Pearson correlation coefficients) with total numbers of BAL cells, percentages of T-cells, and percentages of Ia-positive cells recovered. Findings are consistent with the hypothesis that cell-mediated hypersensitivity is a central mechanism in the pathogenesis of experimental hypersensitivity pneumonitis.


[The prospect of dopaminergic therapy in multiple sclerosis].
Dopamine is a direct mediator of neuroimmune interactions. Recent studies show that by acting on the dopaminergic receptors, it is possible to modulate Th17-immune response, which play a crucial role in the pathogenesis of multiple sclerosis. Dopamine can modulate Th17 cells function as well as dendritic cell-mediated Th17-immune response that allows considering dopaminergic receptors as a new therapeutic target in multiple sclerosis. In this short communication, the prospects of using dopaminergic therapy as a pathogenetic treatment for multiple sclerosis are discussed.


Influence of water temperature on acetylcholinesterase activity in the Pacific tree frog (Hyla regilla).
This investigation evaluated whether acetylcholinesterase (AChE) in Pacific tree frogs (Hyla regilla) from different geographical locations was influenced by different temperatures during early aquatic life stages, independent of pesticide exposure. Tadpoles were collected from both a California coastal pond and a Sierra Nevada mountain range pond, USA. Groups of frogs from each location were raised in temperatures representative of either the Sierra Nevada (8 degrees C) or the coastal (19 degrees C) location. Metamorphs from both locations raised as tadpoles at 19 degrees C had AChE activities of 42.3 and 38.7 nm/min/mg protein, while those raised as tadpoles at 8 degrees C had activities of 26.9 and 28.2 nm/min/mg protein. A two-way analysis of variance revealed temperature to be the significant factor in determining AChE activity (F = 22.3, p < 0.001), although origin was not important (F = 0.09, p = 0.75). Interpretations regarding the influence of pesticides upon AChE activity in Pacific tree frogs must consider the influence of environmental temperature to enable cross-population comparisons.


Selective inhibition of lymphocyte responsiveness to phytohaemagglutinin in patients with Reiter's syndrome.
The influence of synovial fluid from four patients with Reiter's syndrome on lymphocyte responsiveness was studied. On synovial fluid was found which specifically depressed the responsiveness of lymphocytes from patients with Reiter's syndrome to the non-specific mitogen phytohaemagglutinin (PHA). The ratio of the responsiveness of lymphocytes cultured in the presence of foetal calf serum (FCS), compared to those incubated in the Reiter's synovial fluid, was used as a measure of the depression induced by the Reiter's synovial fluid. The mean ratio for eight normals stimulated with PHA was 0-70 (range 0-35-0-96), while for eight patients with Reiter's syndrome, it was 0-13 (range 0-07-0-19). Similar studies done with concanavalin A (con A) showed no difference between lymphocytes from normals (0-73) or patients with Reiter's syndrome (0-67). Chromatography of the Reiter's synovial fluid on a Sepharose 4-B column resulted in the separation of three major fractions, one of which exhibited the inhibitory activity. When this active fraction was absorbed with Reiter's lymphocytes, a loss of the inhibitory activity of the fraction was seen. A similar absorption with normal lymphocytes had no effect. These studies demonstrate that a factor present in the synovial fluid of a patient with Reiter's syndrome reacted specifically with lymphocytes from patients with Reiter's disease and not with lymphocytes from normals. The interaction of this factor with lymphocytes from patients with Reiter's syndrome inhibited the responsiveness of these lymphocytes to PHA but not to con A.


Hepatic lipase- and endothelial lipase-deficiency in mice promotes macrophage-to-feces RCT and HDL antioxidant properties.
Hepatic lipase (HL) and endothelial lipase (EL) are negative regulators of plasma HDL cholesterol (HDLc) levels and presumably could affect two main HDL atheroprotective functions, macrophage-to-feces reverse cholesterol transport (RCT) and HDL antioxidant properties. In this study, we assessed the effects of both HL and EL deficiency on macrophage-specific RCT process and HDL ability to protect against LDL oxidation. HL- and EL-deficient and wild-type mice were injected intraperitoneally with [(3)H]cholesterol-labeled mouse macrophages, after which the appearance of [(3)H]cholesterol in plasma, liver, and feces was determined. The degree of HDL oxidation and the protection of oxidative modification of LDL co-incubated with HDL were evaluated by measuring conjugated diene kinetics. Plasma levels of HDLc, HDL phospholipids, apoA-I, and platelet-activated factor acetyl-hydrolase were increased in both HL- and EL-deficient mice. These genetically modified mice displayed increased levels of radiolabeled, HDL-bound [(3)H]cholesterol 48h after the label injection. The magnitude of macrophage-derived [(3)H]cholesterol in feces was also increased in both the HL- and EL-deficient mice. HDL from the HL- and EL-deficient mice was less prone to oxidation and had a higher ability to protect LDL from oxidation, compared with the HDL derived from the wild-type mice. These changes were correlated with plasma apoA-I and apoA-I/HDL total protein levels. In conclusion, targeted inactivation of both HL and EL in mice promoted macrophage-to-feces RCT and enhanced HDL antioxidant properties.


Vaso-occlusion in sickle cell disease: pathophysiology of the microvascular circulation.
Microvascular dysfunction accounts for the major morbidity and contributes to the mortality among patients with sickle cell hemoglobinopathies. We summarize the microcirculatory dynamics of red cells in sickle cell disease. An overview of the physiological attributes of the microcirculation is presented. The microcirculatory module is a unique organic entity within the tissue domain, which is concerned with the functional exchange of substances between the blood and the tissue environment. The impairment in deformability of sickle red cells and their heterogeneity cause them to show abnormal microvascular flow dynamics that, in turn, contribute to derangement of the microvascular bed. Studies of experimental models in animals have employed the microcirculation of the mesentery, the cremaster muscle, and the mesoappendix. These studies showed the rheological disequilibrium that results as sickle cells course through successive segments of the arterioles, capillaries, and venules. Direct in vivo microscopic observations in human subjects, with analysis and quantitation of the nailfold and bulbar conjunctival capillaries, have also provided useful information as to the adverse effects of sickling on the microcirculation. Sickle cell vaso-occlusion has three phases--initiation, propagation, and resolution. This framework provides a basis for testable hypotheses for verification in appropriately designed experiments. In this context, the determinants of the microvascular flow of erythrocytes in sickle cell disease are emphasized.


Virus-like particules in the poison glant of the parasitic wasp Opius concolor.
Virus-like particles (VLP's) have been found in the poison glands of adult females of the parasitic wasp Opius concolor Szèpl. (Hymenoptera, Braconidae). These VLP's are found in the secretory cells either free in the cytoplasm or within cytoplasmic vesicles, sometimes associated to a secretory apparatus. Negative staining of these VLP's has revealed the occurrence of two different particles. The first type exhibits icosahedral symmetry (diameter around 70nm) and hollow surface spikes, this morphology being typical of the genus Cypovirus (Reoviridae). The other type is pleomorphic and presents an envelope with clubshaped projections (diameter ranging from 30 to 60nm), as classical textbook examples of Coronaviruses, but smaller. Function and full characterisation of these particles are not yet known.


Three-dimensional imaging of rhodamine 123 fluorescence distribution in human melanoma cells by means of confocal laser scanning microscopy.
Three-dimensional (3D) imaging of intracellular rhodamine 123 fluorescence distribution was performed by means of confocal laser scanning microscopy (CLSM). Human IGR melanoma cells grown in monolayer or multicellular spheroid culture were studied for elucidating mitochondrial membrane potential characteristics, and cell and nucleus volume dimensions. Microspheres 6 microns in diameter loaded with rhodamine B were used to calibrate our instruments for performing 3D imaging of optical sections as obtained by CLSM. Accurate optical slicing is only possible taking into consideration the physical characteristics of the objectives used like chromatic and spherical aberrations, depth discrimination or cover slip correction and the temperature dependence of the immersion medium. While 3D imaging of optical slices can be carried out showing the original shape of the object being tested without physical distortion, 3D images of microspheres show well-reproducible structures of rhodamine B fluorescence. These can be explained by a superposition of two effects, namely scattering of the fluorescence light and a gradient of the electromagnetic field strength of the laser beam due to the shape of the object. 3D imaging of optical slices of IGR cells in monolayer or multicellular spheroid culture, which have been loaded with rhodamine 123, show the location of the dye predominantly within the cytoplasm of the cells with a remarkable heterogeneity of fluorescence intensity within and between single cells, indicating differences in the mitochondrial membrane potential and thus in the metabolic activity. Due to the heterogeneity of the cell shape the cell nucleus occupies between 4 and 14% of the total cell volume. These data reveal calibrated 3D imaging as a valuable noninvasive tool to visualize the heterogeneity of cell parameters under different cell culture conditions.


Sex-related differences in hospital admissions attributed to adverse drug reactions in the Netherlands.
Women are more at risk for developing adverse drug reactions (ADRs) due to differences in pharmacokinetics, pharmacodynamics and drug use. ADRs regularly lead to hospital admissions. There are differences between the sexes in hospital admissions attributed to ADRs. The risk of being hospitalized with an ADR varies between the sexes in the type of reaction and the causative drug. Adverse drug reactions (ADRs) are a major burden in health care, regularly leading to hospital admission, morbidity or death. Women tend to have a higher risk of adverse drug reactions with a 1.5 to 1.7-fold greater risk than men. Our primary aim was to study differences in ADR-related hospitalizations between the sexes. We conducted a nationwide study of all ADR-related hospitalizations in the period between 2000 and 2005 in the Netherlands, which were selected from all 9,287,162 hospital admissions in this period. ADR-drug group combinations with at least 50 admissions in one of the sexes were selected. Relative risks and confidence intervals were calculated with respect to total admissions and total prescriptions with men as reference. In total, 0.41% of the 4,236,368 admissions in men (95% CI 0.40, 0.42%) and 0.47% of the 5,050,794 admissions in women (95% CI 0.46, 0.48%) were attributed to an ADR by medical specialists (57% of all ADR-related admissions were in women). Differences between the sexes in risk for ADR-related hospitalization were found for antineoplastic and immunosuppressive drugs, antirheumatics, anticoagulants and salicylates, cardiovascular and neurological drugs, steroids and antibiotics. In certain drug categories, risks for hospitalization changed after taking into account total drug prescriptions. In all different drug classes, significant differences exist between the sexes in ADR-related hospital admissions. Cardiovascular drugs account for the most pronounced differences between men and women. More research is needed to explain the clear sex differences in ADR-related hospital admissions.


Decreased sperm number and motile activity on the F1 offspring maternally exposed to butyl p-hydroxybenzoic acid (butyl paraben).
Butyl p-hydroxybenzoic acid (butyl paraben, BP) is widely used as a preservative in food and cosmetic products. Routledge et al showed that BP is weakly estrogenic in both in vitro and in vivo (rat uterotrophic) analyses. We investigated whether maternal exposures to BP during gestation and lactation periods affected the development of the reproductive organs of the F1 offspring. Pregnant Sprague-Dawley rats were injected subcutaneously with 100 or 200 mg/kg of BP from gestation day (GD) 6 to postnatal day (PND) 20. In the group exposed to 200 mg/kg of BP, the proportion of pups born alive and the proportion of pups surviving to weaning were decreased. The body weights of female offspring were significantly decreased at PND 49. The weights of testes, seminal vesicles and prostate glands were significantly decreased in rats exposed to 100 mg/kg of BP on PND 49. In contrast, the weights of female reproductive organs were not affected by BP. The sperm count and the sperm motile activity in the epididymis were significantly decreased at doses of 100 and 200 mg/kg of BP. In accordance with the sperm count in the epididymis, the number of round spermatids and elongated spermatids in the seminiferous tubule (stage VII) were significantly decreased by BP. Testicular expression of estrogen receptor (ER)-alpha and ER-beta mRNA was significantly increased in 200 mg/kg of BP treated group at PND 90. Taken together, these results indicated that maternal exposure of BP might have adverse effects on the F1 male offspring.


Microbial composition of a hydropower cooling water system reveals thermophilic bacteria with a possible role in primary biofilm formation.
Microfouling, ie biofilm formation on surfaces, can have an economic impact and requires costly maintenance in water-powered energy generation systems. In this study, the microbiota of a cooling system (filter and heat exchanger) in the Irapé hydroelectric power plant in Brazil was examined. The goal was to identify bacteria that could be targeted to more efficiently reduce biofilm formation. Two sampling campaigns were made corresponding to two well-defined seasons of the Brazilian Cerrado biome: the dry (campaign 1) and the wet (campaign 2). Microfouling communities varied considerably over time in samples obtained at different times after the last clearance of the heat exchanger. The thermophilic bacteria Meiothermus, Thermomonas and Symbiobacterium were exclusive and abundant in the microfouling of the heat exchanger in campaign 2, while methanotrophs and iron-reducing bacteria were abundant only in filter sediments. These findings could help to guide strategies for ecofriendly measures to reduce biofilm fouling in hydroelectric power plants, minimizing environmental and economic losses.


JAK1-STAT1-STAT3, a key pathway promoting proliferation and preventing premature differentiation of myoblasts.
Skeletal muscle stem cell-derived myoblasts are mainly responsible for postnatal muscle growth and injury-induced muscle regeneration. However, the cellular signaling pathways controlling the proliferation and differentiation of myoblasts are not fully understood. We demonstrate that Janus kinase 1 (JAK1) is required for myoblast proliferation and that it also functions as a checkpoint to prevent myoblasts from premature differentiation. Deliberate knockdown of JAK1 in both primary and immortalized myoblasts induces precocious myogenic differentiation with a concomitant reduction in cell proliferation. This is caused, in part, by an accelerated induction of MyoD, myocyte enhancer-binding factor 2 (MEF2), p21Cip1, and p27Kip1, a faster down-regulation of Id1, and an increase in MEF2-dependent gene transcription. Downstream of JAK1, of all the signal transducer and activator of transcriptions (STATs) present in myoblasts, we find that only STAT1 knockdown promotes myogenic differentiation in both primary and immortalized myoblasts. Leukemia inhibitory factor stimulates myoblast proliferation and represses differentiation via JAK1-STAT1-STAT3. Thus, JAK1-STAT1-STAT3 constitutes a signaling pathway that promotes myoblast proliferation and prevents premature myoblast differentiation.


Experiences of the Initial Phase Implementation of the STAMINA-Model in Perioperative Context Addressing Environmental Issues Systematically-A Qualitative Study.
(1) Background: Challenges in perioperative settings put demands on staff working with systematic work environment management. A support model, STAMINA (Structured and Time-effective Approach through Methods for an Inclusive and Active working life), was implemented in a hospital in Sweden, to help staff address environmental issues systematically. The aim was to describe the experiences of the initial phase of implementation of the adapted STAMINA model in perioperative context. (2) Methods: Qualitative individual interviews were held with 14 managers and employees (three men and 11 women). Data were analysed by systematic text condensation. (3) Results: Five themes were identified: Limited knowledge of the model and the implementation process; scepticism, lack of confidence in the model and a passive attitude; the model offered increased participation; the culture in the organization-to understand one's role as employees and managers; and endurance and feedback are key factors for success in the implementation process. (4) Conclusions: Scepticism turned to positive attitude by recognising that the STAMINA model offered increased participation. In order to have successful implementation, the organisational culture must be taken into consideration by giving the employees increased responsibilities and timely feedbacks. Role description, goal definition, feedback, and sticking to one model are key factors for success.


Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors.
Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to untargeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.


Clinical profile and severity of Plasmodium vivax and falciparum malaria in hospitalized children from North India.
Malaria is the most common parasitic infection in children and the most common cause of mortality by vector-borne disease in tropical countries. In these endemic countries there is limited published literature on the clinical profile and severity of Plasmodium vivax malaria in children. We highlight the clinical presentations and severity of malaria in children belonging to Uttar Pradesh, North India Methods: This observational study was conducted in a tertiary care hospital, in Moradabad, western Uttar Pradesh, India. Children (aged 6 months-18 years) hospitalized from June 2019 to May 2020 with a clinical picture consistent with malaria along with a positive rapid malaria antigen test (RMAT) and/or positive peripheral blood smear for malaria were enrolled. All data about the clinical profile and laboratory features were recorded. Results were analyzed for significance using appropriate statistical tests for continuous and categorical data. One hundred children were enrolled in this study; 59 cases had Plasmodium vivax (PV) malaria, 33 cases had Plasmodium falciparum (PF) malaria, and 8 cases had mixed infections (both PV and PF). Among 59 children with P V malaria, 44 (74%) had severe malaria and 15 (26%) had uncomplicated malaria. Severe malarial anaemia (43.2%), followed by jaundice (36.4%), impaired renal function (21.6%), significant bleeding (18.9%), shock (18.9%), and prostration (16.2%), were the main severity parameters of malaria among these hospitalised children. Impaired renal function (P-value = 0.01) and unconsciousness (P-value = 0.02) were more frequent in Plasmodium falciparum cases. Other severity parameters were not significant between the vivax and falciparum species. We conclude that a significant proportion of severe malaria was caused by Plasmodium vivax in this region, where both species coexist. Plasmodium vivax malaria is no longer the benign entity it was around ten years ago in hospitalised children. Severe malarial anaemia was the most common severity parameter found in both Plasmodium vivax and P. falciparum species. The clinical presentation and a change in the severity parameters in vivax malaria indicate a recent shift in the disease severity from benign to fatal.


Coarse-grained molecular dynamics study of cyclic peptide nanotube insertion into a lipid bilayer.
Coarse-grained (CG) molecular dynamics (MD) simulations are performed to study the insertion of cyclic peptide nanotubes into cell membranes and to examine whether cyclic peptide nanotubes can function as an ion channel and thereby as an antibacterial agent. To do so, the two coarse-grained (CG) models for lipid molecules and for proteins developed by Marrink et al. (J. Phys. Chem. B 2004, 108, 750) and by Shih et al. (J. Phys. Chem. B 2006, 110, 3674), respectively, were extended and modified. These CG models were verified by performing CG MD and all-atom (AA) MD simulations for a cyclic peptide nanotube, 8 x cyclo[(-d-Ala-l-Glu-d-Ala-l-Gln-)2], in water and by comparing the results from the two simulations. Comparison between static and dynamic (water transport) properties obtained from both simulations shows good agreement. To study nanotube insertion, a CG cyclic peptide nanotube, 8 x cyclo[(-Trp-d-Leu-)4], was prepared above the surface of a CG DPPC lipid bilayer, restrained with constraints, and equilibrated, and then a series of CG MD simulations were carried out by lifting the constraints imposed on the nanotube. The CG MD simulations show that the cyclic peptide nanotube spontaneously inserts into and reorients inside the lipid bilayer. After insertion, the long axis of the cyclic peptide nanotube is aligned approximately perpendicular to the bilayer plane indicating that the nanotube can function as an ion channel and as an antibacterial agent. Tilt structures of the cyclic peptide nanotubes inside the lipid bilayer are found to be in agreement with experiment and earlier AA simulations. Lipid flip-flop, a migration of lipid molecules from one leaflet to the other leaflet of the lipid bilayer, is also observed from the CG MD simulations. Finally, the CG MD simulations reveal that a lipid headgroup can be inserted into the cyclic peptide nanotube. This process is confirmed by an AA MD simulation.


Effect of Educational Program on Knowledge, Skills, and Personal Preparedness for Disasters Among Emergency Nurses: A Quasi-Experimental Study.
Continuous nursing education has a significant correlation with increasing knowledge, improving skills, and personal preparedness for disasters among nurses which leads to a decrease in mortality rate and enhances the quality of care. However, there is limited literature evaluating the effect of educational programs on the knowledge, skills, and personal preparedness for disaster preparedness among emergency nurses at Arab countries including, Jordan. This study evaluated the effect of an educational program on knowledge, skills, and personal preparedness for disasters among emergency nurses. A quasi-experimental study and one-group pretest-posttest design was used. A convenience sample was adopted to recruit registered nurses who are working in emergency rooms in the private and government health sectors in Jordan (N = 50). This study was conducted between May and June 2021. The intervention included an educational program consisting of 5 topics about disasters. The participants attended this program for 8 h over 1 week via Zoom application. There were significant differences between the pre-post educational intervention for knowledge (t = 4.79, P ≤ .001), skills (t = 6.66, P ≤ .001), and personal preparedness (t = 9.56, P ≤ .001) for disasters. These findings suggested the importance of implementing continuous education and training programs for emergency nurses about disasters due to increasing frequency of disasters worldwide.


Revisiting the armed-disarmed concept: the importance of anomeric configuration in the activation of S-benzoxazolyl glycosides.
The unexpectedly high reactivity of a (2-benzoxazolyl) per-O-benzoyl-beta-D-thioglucoside and related donors in reactions promoted by copper(II) trifluoromethanesulfonate is revealed, by comparison with the unreactive alpha-anomer, to be the result of neighboring group participation. Revision of the armed-disarmed concept for glycosyl donors is not required.


[Schizophrenia-like symptoms in the Westphal-Strümpell variation of Wilson disease].
Wilson's disease is a rare, autosomal recessive disorder of copper metabolism due to low serum ceruloplasm, resulting in increased copper deposition, especially in the liver and basal ganglia in the brain. The pseudosclerotic type of Wilson's disease, also known as the Westphal-Strümpell form, is distinguished by positional tremor, ataxia and dysarthria as the main symptoms. We use the example of a 23-year-old patient whose neurological symptoms were preceded by a long history of a schizophrenic-like disorder. Clinical symptoms are presented. MRI, SPECT and PET images are illustrated. Therapy and outcome are discussed.


Evolved gas, pain, the power law, and probability of hypobaric decompression sickness.
The intensity of a pain-only decompression sickness (DCS) symptom with respect to time at altitude increases, peaks, and then declines in some cases. A similar pattern is also seen in a graph of the probability density function [f(t)] for DCS. The f(t) is the proportion of DCS per unit time with respect to time at altitude. The integration of f(t) with respect to time provides the cumulative probability of DCS [P(DCS)]. We suspect that the perceived intensity of pain with a given stimulus intensity is related to the P(DCS); it may be related to the intensity of the stimulus to a power (alpha). Our stimuli are defined as pressure ratio [PR = (phi P1N2/ P2)-11] or pressure difference [delta P = phi P1N2-P2], where phi P1N2 is the N2 partial pressure calculated in the 360 min half-time (t1/2) compartment or t1/2 is estimated with other parameters and P2 is ambient pressure after the ascent. Both stimuli represent a potential released volume of gas. We tested the null hypothesis that alpha > 1 was no better than alpha = 1 in PR alpha and delta P alpha in a log logistic survival analysis of 1085 exposures in hypobaric chambers. The log likelihood number increased from -1198 for alpha = 0 for the null model to -724 for PR alpha when alpha = 3.52 with a 42 min t1/2 and -714 for delta P alpha when alpha = 8.44 with a 91 min t1/2. We conclude that the improvement in our expressions for decompression dose with alpha > 1 is not by random chance and that alpha may link the physics of gas evolution to the biology of pain perception. Because of our empirical approach, we do not exclude other possible interpretations.


Influence of root embedment material and periodontal ligament simulation on fracture resistance tests.
The aim of this study was to evaluate the influence of the embedment material and periodontal ligament simulation on fracture resistance of bovine teeth. Eighty bovine incisor teeth were randomized into 8 groups (n = 10), embedded in acrylic or polystyrene resin using 4 types of periodontal ligament simulation: 1--absence of the ligament; 2--polyether impression material; 3--polysulfide impression material; 4--polyurethane elastomeric material. The specimens were stored at 370C and 100% humidity for 24 hours. Specimens were submitted to tangential load on the palatal surface at 0.5 mm/minute crosshead speed until fracture. The fracture modes were analyzed as follows: 1--coronal fracture; 2--cemento-enamel junction fracture; 3--partial root fracture; 4--total root fracture. Statistical analyses by two-way ANOVA and Tukey's test were applied (p < 0.05). The results showed that root embedment method and periodontal ligament simulation have a significant effect on fracture resistance. Artificial periodontal ligament modified the fracture modes.


A multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus.
Monkeypox viral infection is an emerging threat and a major concern for the human population. The lack of drug molecules to treat this disease may worsen the problem. Identifying potential drug targets can significantly improve the process of developing potent drug molecules for treating monkeypox. The proteins responsible for viral replication are attractive drug targets. Identifying potential inhibitors from known drug molecules that target these proteins can be key to finding a cure for monkeypox. In this work, two viral proteins, DNA-dependent RNA polymerase (DdRp) and viral core cysteine proteinase, were considered as potential drug targets. Sixteen antibiotic drugs from the tetracycline class were screened against both viral proteins through high-throughput virtual screening. These tetracycline class of antibiotic drugs have the ability to inhibit bacterial protein synthesis, which makes these antibiotics drugs a prominent candidate for drug repurposing. Based on the screening result obtained against DdRp, top two compounds, namely Tigecycline and Eravacycline with docking scores of - 8.88 and - 7.87 kcal/mol, respectively, were selected for further analysis. Omadacycline and minocycline, with docking scores of - 10.60 and - 7.51 kcal/mol, are the top two compounds obtained after screening proteinase with the drug library. These compounds, along with reference compounds GTP for DdRp and tecovirimat for proteinase, were used to form protein-ligand complexes, followed by their evaluation through a 300 ns molecular dynamic simulation. The MM/GBSA binding free energy calculation and principal components analysis of these selected complexes were also conducted for understanding the dynamic stability and binding affinity of these compounds with respective target proteins. Overall, this study demonstrates the repurposing of tetracycline-derived drugs as a therapeutic solution for monkeypox viral infection.


Psychological distress and the perception of radiation risks: the Fukushima health management survey.
To assess relationships between the perception of radiation risks and psychological distress among evacuees from the Fukushima nuclear power plant disaster. We analysed cross-sectional data from a survey of evacuees conducted in 2012. Psychological distress was classified as present or absent based on the K6 scale. Respondents recorded their views about the health risks of exposure to ionizing radiation, including immediate, delayed and genetic (inherited) health effects, on a four-point Likert scale. We examined associations between psychological distress and risk perception in logistic regression models. Age, gender, educational attainment, history of mental illness and the consequences of the disaster for employment and living conditions were potential confounders. Out of the 180,604 people who received the questionnaire, we included 59,807 responses in our sample. There were 8717 respondents reporting psychological distress. Respondents who believed that radiation exposure was very likely to cause health effects were significantly more likely to be psychologically distressed than other respondents: odds ratio (OR) 1.64 (99.9% confidence interval, CI: 1.42-1.89) for immediate effects; OR: 1.48 (99.9% CI: 1.32-1.67) for delayed effects and OR: 2.17 (99.9% CI: 1.94-2.42) for genetic (inherited) effects. Similar results were obtained after controlling for individual characteristics and disaster-related stressors. Among evacuees of the Fukushima nuclear disaster, concern about radiation risks was associated with psychological distress.


Assessment of different fitting methods for in-vivo bi-component T2* analysis of human patellar tendon in magnetic resonance imaging.
To investigate the robustness of four fitting methods for bi-component effective spin-spin T2 (T2*) relaxation time analysis of human patellar tendon. A three-dimensional (3D) cone ultra-short echo-time (UTE) sequence was performed on the knees of ten healthy volunteers at 3.0T. Four fitting methods incorporating either Gaussian or Rician noise distribution were used for voxel-by-voxel bi-component T2* analysis of the patellar tendon. The T2* for the short relaxing (T**,s ) and long relaxing (T*2,l ) water components and the fraction of the short relaxing water component (fs ) were measured, and different fitting methods were compared using Friedman's and Wilcoxon signed rank tests. A numerical simulation study was also performed to predict the accuracy and precision of bi-component T2* parameter estimation in tendon at different signal-to-noise ratios (SNR) levels. The average T*2,s , T*2,l , fs of human patellar tendon were 1.5ms, 30ms, and 80% respectively. Incorporating different noise models and fitting methods influenced the measured bi-component T2* parameters. Fitting methods incorporating Rician noise were superior to traditional fitting methods for bi-component T2* analysis especially at lower SNR. fs and T*2,s were less sensitive than T*2,1 to noise at even moderate and low SNR. The result of the in-vivo bi-component T2* analysis of tendon agreed well with numerical simulations. Our study demonstrated the use of a 3D cone UTE sequence to perform in vivo voxel-by-voxel bi-component T2* analysis of human patellar tendon. Incorporating Rician noise was useful for improving bi-component T2* analysis especially at lower SNR. IV.


Selective and Sensitive Fluorometric Determination of Piroxicam Based on Nitrogen-doped Graphene Quantum Dots and Gold Nanoparticles Coated with Phenylalanine.
In this study, a sensitive fluorimetric method is proposed for the determination of piroxicam using nitrogen graphene quantum dots (N-GQDs) and gold nanoparticles coated with phenylalanine. The fluorescence emission of N-GQDs at 440 nm decreases with the increase of gold nanoparticles coated with phenylalanine. However, the addition of piroxicam causes the release of gold nanoparticles from the surface of quantum dots followed by the retrieval of the fluorescence emission of N-GQDs. Under the optimum conditions, the calibration graph was linear in the concentration range of 2.0-35.0 nmol L-1 for piroxicam with a limit of detection of 0.11 nmol L-1. The developed method was successfully applied for the determination of piroxicam in urine and serum samples.


The plant-specific ssDNA binding protein OSB1 is involved in the stoichiometric transmission of mitochondrial DNA in Arabidopsis.
Plant mitochondrial genomes exist in a natural state of heteroplasmy, in which substoichiometric levels of alternative mitochondrial DNA (mtDNA) molecules coexist with the main genome. These subgenomes either replicate autonomously or are created by infrequent recombination events. We found that Arabidopsis thaliana OSB1 (for Organellar Single-stranded DNA Binding protein1) is required for correct stoichiometric mtDNA transmission. OSB1 is part of a family of plant-specific DNA binding proteins that are characterized by a novel motif that is required for single-stranded DNA binding. The OSB1 protein is targeted to mitochondria, and promoter-beta-glucuronidase fusion showed that the gene is expressed in budding lateral roots, mature pollen, and the embryo sac of unfertilized ovules. OSB1 T-DNA insertion mutants accumulate mtDNA homologous recombination products and develop phenotypes of leaf variegation and distortion. The mtDNA rearrangements occur in two steps: first, homozygous mutants accumulate subgenomic levels of homologous recombination products; second, in subsequent generations, one of the recombination products becomes predominant. After the second step, the process is no longer reversible by backcrossing. Thus, OSB1 participates in controlling the stoichiometry of alternative mtDNA forms generated by recombination. This regulation could take place in gametophytic tissues to ensure the transmission of a functional mitochondrial genome.


Decomposing Disability Inequality in Unmet Healthcare Needs and Preventable Hospitalizations: An Analysis of the Korea Health Panel.
Objectives: This study examines the inequality between people with and without disabilities regarding unmet healthcare needs and preventable hospitalization. Methods: We used the Korea Health Panel of 2016-2018; the final analytical observations were 43,512, including 6.95% of persons with disabilities. We examined the differences in contributors to the two dependent variables and decomposed the observed differences into explained and unexplained components using the Oaxaca-Blinder approach. Results: Unmet healthcare needs and preventable hospitalizations were 5.6% p (15.36% vs. 9.76%) and 0.68% p (1.82% vs. 0.61%), respectively, higher in people with disabilities than in those without, of which 48% and 35% were due to characteristics that the individual variables cannot explain. Decomposition of the distributional effect showed that sex, age, and chronic disease significantly increased disparities for unmet healthcare needs and preventable hospitalization. Socioeconomic factors such as income level and Medical aid significantly increased the disabled-non-disabled disparities for unmet healthcare needs. Conclusion: Socioeconomic conditions increased the disparities, but around 35%-48% of the disparities in unmet healthcare needs and preventable hospitalization were due to unexplained factors, such as environmental barriers.


Presence and absence of the microsomal beta-glucuronidase in mice correlates with differences in the processing of the lysosomal enzyme.
In some tissues such as liver and kidney, beta-glucuronidase is present not only in the lysosomes but also in the microsomes. Both enzymes are coded by the same structural gene. The function of the microsomal enzyme is still unclear. We have observed in primary cultures of mouse hepatocytes that the microsomal enzyme disappeared to a trace within 5 days after plating cells. This change of intracellular localization coincided with a change of the isoelectric focusing pattern of the lysosomal beta-glucuronidase. Within the multiple banding pattern of the lysosomal enzyme, a faintly staining group of bands in the more acidic range (mean pI 5.4) became more pronounced while a major group (mean pI 5.9) faded slightly. The correlation between the presence or absence of the microsomal beta-glucuronidase and distinct proportions of the two lysosomal enzyme forms was confirmed in vivo. The less acidic form (pI 5.9) prevailed in the presence (kidney, liver), the more acidic form (pI 5.4) in the absence of the microsomal enzyme (spleen). The two lysosomal forms differed also in their apparent molecular weight by approx. 1500 (Mr 71 500 versus 73 000). In order to elucidate the biosynthetic relationship between the microsomal enzyme and the two lysosomal enzyme forms we interfered with their processing in cultured hepatocytes. The addition of the protease/esterase inhibitor phenyl-methyl-sulfonyl-fluoride caused the disappearance of the microsomal and the appearance of the acidic pI 5.4 lysosomal enzyme within 24 h; with chloroquine, the microsomal enzyme remained nd no lysosomal pI 5.4 enzyme appeared.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of Somatic Mutations That Affect Neoantigens in Non-Small Cell Lung Cancer.
Immune checkpoint inhibitors (ICIs) have recently emerged as an important option for treating patients with advanced non-small cell lung cancer (NSCLC). Neoantigens are important biomarkers and potential immunotherapy targets that play important roles in the prognosis and treatment of patients with NSCLC. This study aimed to evaluate and characterize the relationships between somatic mutations and potential neoantigens in specimens from patients who underwent surgical treatment for NSCLC. This prospective study evaluated specimens from patients with NSCLC who underwent surgical treatment at the Peking Union Medical College, China, from June 2019 to September 2019. Whole-exome sequencing was performed for tumor tissues and corresponding normal tissues. Candidate neoantigens were predicted using generative software, and the relationships between various mutation characteristics and number of neoantigens were evaluated. Neoantigen-related gene mutations were less frequent than mutations affecting the whole genome. Genes with high neoantigen burden had more types and higher frequencies of mutations. The number of candidate neoantigens was positively correlated with missense mutations, code shift insertions/deletions, split-site variations, and nonsense mutations. However, in the multiple linear regression analysis, only missense mutations were positively correlated with the number of neoantigens. The number of neoantigens was also positively correlated with base transversions (A>C/C>A, T>G/G>T, and C>G/G>C) and negatively correlated with base transitions (A>G/G>A and C>T/T>C). The number of candidate neoantigens in NSCLC specimens was associated with mutation frequency, type of mutation, and type of base substitution.


Automatic diagnosis of neuro-muscular diseases using neural network.
An automatic diagnostic tool for neuromuscular diseases, based on the feature extraction and classification of myoelectric patterns using neural network is described. Electromyogram (EMG) signals are extracted from the patients during maximal contraction using needle electrodes. This EMG signal is digitized at a rate of 1000 samples/second. The myoelectric signal is divided into many time segments. Five time domain features are extracted from each of these segments and are averaged over the segments to obtain one feature set. This is applied to the neural network for classification. Results are presented for the diagnosis of polymyositis.


Argon laser iridotomy: an experimental and clinical study.
Iridotomies were made in rabbit and human eyes using a continuous wave argon laser. Several of these have been studied histologically to determine the short- and long-term effects on the iris, cornea, lens and retina. Thirty-three eyes of patients with angle-closure glaucoma were treated by argon laser iridotomy and followed for periods of up to twelve months. In two eyes, planned cataract surgery was performed shortly after the laser iridotomy and histologic specimens of the iris were examined. From the experimental and clinical studies, an evaluation was made of the complications and clinical usefulness of the continuous wave argon laser as a means to produce iridotomies for the treatment of angle-closure glaucoma. Further long-term controlled studies are recommended to document the role of laser iridotomy.


Characterization of the human tumor and normal tissue reactivity of the KS1/4 monoclonal antibody.
The tissue and tumor distribution of the antigen recognized by monoclonal antibody KS1/4 was determined by a combination of immunoperoxidase techniques, flow cytometric analyses and solid phase enzyme-linked immunoassays. These data document that the KS1/4 antigen is expressed in many epithelial malignancies and normal epithelial surfaces suggesting that this antigen represents an epithelial/epithelial malignancy marker.


The role of beta-adrenergic activity in the production of cardiac and aortic arch anomalies in chick embryos.
The sympathomimetic amines isoproterenol, epinephrine, norepinephrine, and phenylephrine are structural derivatives of beta-phenylethylamine and have proportionately different effects on alpha- and beta-adrenergic receptors. Chick embryos in ovo were each administered a single dose of one of these compounds at concentrations ranging from 0.4 times 10(-9) to 20 times 10(-9) mol/5 mul saline during Hamburger and Hamilton stages 20-27. In other experiments embryos were pretreated with the beta-antagonist propranolol and subsequently administered isoproterenol. 743 cardiovascular anomalies were produced. The production of cardiovascular anomalies was proportional to the degree of beta-adrenergic activity of each drug. The frequency of anomalies was significantly reduced by pretreatment with propranolol. At all concentrations tested the anomaly rate was greater in chick embryos receiving an experimental compound than in controls. The general types of anomalies included aortic arch defects, ventricular septal defect, double outlet right ventricle, aortic hypoplasia, and truncus arteriosus. These results demonstrate that activation of the beta-adrenergic receptor mechanism is directly related to the cardiovascular anomalies produced in the chick embryos.


Asymmetric effects of sudden changes in timbre on auditory stream segregation.
Two experiments explored the effects of abrupt transitions in timbral properties [amplitude modulation (AM), pure tones vs narrow-band noises, and attack/decay envelope] on streaming. Listeners reported continuously the number of streams heard during 18-s-long alternating low- and high-frequency (LHL-) sequences (frequency separation: 2-6 semitones) that underwent a coherent transition at 6 s or remained unchanged. In experiment 1, triplets comprised unmodulated pure tones or 100%-depth AM was created using narrowly spaced tone pairs (dyads: 30- or 50-Hz modulation). In experiment 2, triplets comprised narrow-band noises, dyads, or pure tones with quasi-trapezoidal envelopes (10/80/10 ms), fast attacks and slow decays (10/90 ms), or vice versa (90/10 ms). Abrupt transitions led to direction-dependent changes in stream segregation. Transitions from modulated to unmodulated (or slower-modulated) tones, from noise bands to pure tones, or from slow- to fast-attack tones typically caused substantial loss of segregation (resetting), whereas transitions in the opposite direction mostly caused less or no resetting. Furthermore, for the smallest frequency separation, transitions in the latter direction usually led to increased segregation (overshoot). Overall, the results are reminiscent of the perceptual asymmetries found in auditory search for targets with or without a salient additional feature (or greater activation of that feature).


A prospective study of highly active antiretroviral therapy in Indian human immunodeficiency virus positive patients.
There are no studies performed in India on the safety of highly active antiretroviral therapy (HAART) combinations which focus on the base-line CD4+ T-cell count. Further, no data on risk factors for Adverse drug reactions (ADRs) to HAART and there is a lack of data on CD4+ T-cell count recovery after HAART. The aim of this study was to assess risk factors for ADRs to HAART. We also compared the efficacy of HAART combinations with respect to base-line CD4+ T-cell count and CD4+ T-cell counts recovery in Indian HIV positive patients. A prospective active surveillance study was adopted at the Antiretroviral Therapy (ART) Centre, District Government Hospital, Udupi, India. HIV-infected patients were intensively monitored to identify risk factors associated with ADRs to HAART from August 2009 to May 2012. The study protocol was approved by the University ethics committee. Baseline CD4+ T-cell count before initiation of HAART and thereafter at every six months of regular follow-up up to 24 months duration was included for comparison. Multivariate logistic regression analysis was used to identify predictors of high risk factors of ADRs. CD4+ T-cell count recovery after HAART from base-line CD4+ T-cell count in different HAART groups was analyzed by test of between-subject effects. P-value <0.05 was considered as statistically significant. A total of 1982 HIV positive patients were enrolled with 1181 (59.6%) males, and 801 (40.4%) females. On multivariate logistic regression analysis, four factors were found to be predictors of high-risk factors for ADRs to HAART: 1) CD4+ T-cell counts, 2) female gender, 3) polypharmacy and 4) opportunistic infections. Between HAART groups, a mean increase of 98 cells/μl of CD4+ T-cell counts recovery was seen in the 3TC + NVP + D4T group (p < 0.001) at 24 months of regular follow-up. In India, Clinician should take into consideration all possible risk factors associated with the use of HAART in order to avoid and minimize ADRs. As initial CD4+ T-cell count and age of patient decides the rise of CD4+ T-cell counts with HAART. HAART should be initiated at the earliest age in order to attain maximum CD4+ T-cell counts recovery.


Improving compliance with cervical cancer screening guidelines.
Current cervical cancer screening guidelines for the care of healthy women include HPV cotesting with all Papanicolaou (Pap) smears after the age of 30. To improve compliance with current guidelines, we instituted two processes: first, simplifying the ordering process to a single order for Pap smear plus HPV cotesting using an electronic medical record system (EMR); and second, providing education for clinic staff. Baseline and postintervention data were collected by retrospective chart review. Patients were selected during three intervals: prior to the transition to Epic EMR, after the transition to Epic, and after an educational intervention. Compliance with standard guidelines was evaluated in relation to the trial intervals, type of provider, patient age, and duration from the previous Pap smear. Provider type was analyzed by considering gynecologists versus nongynecologist providers, and physicians versus mid-level providers. Overall, the percentage of compliance with HPV test ordering did not differ (P = 0.21) between intervals. Univariate analyses performed to identify factors likely to be associated with the practice of ordering HPV cotesting only involved the type of provider. In conclusion, transition to Epic and a training session had minimal impact on compliance with ordering HPV cotesting at the time of a Pap smear except among family practice physicians, who did significantly improve their compliance rate. Gynecologists and mid-level providers were more compliant with ordering HPV cotesting throughout, but did not significantly improve after the interventions.


Cognitive imitation in rhesus macaques.
Experiments on imitation typically evaluate a student's ability to copy some feature of an expert's motor behavior. Here, we describe a type of observational learning in which a student copies a cognitive rule rather than a specific motor action. Two rhesus macaques were trained to respond, in a prescribed order, to different sets of photographs that were displayed on a touch-sensitive monitor. Because the position of the photographs varied randomly from trial to trial, sequences could not be learned by motor imitation. Both monkeys learned new sequences more rapidly after observing an expert execute those sequences than when they had to learn new sequences entirely by trial and error.


Drug prescribing pattern of interns at a government healthcare centre in northern India.
Prescribing habits of interns posted at a primary health centre for a period of 2 months (January 1994 and February 1994) were studied. Among the 1457 prescriptions collected, the average number of drugs per prescription was 2.47. The commonest groups of drugs prescribed were antibiotics (33.9%), analgesics and anti-inflammatories (17.0%), vitamins (13.0%), cough syrups (10.5%) and antihistamines (8.6%). The use of injectables was uncommon (0.9%). Most of the drugs prescribed were from the local drugs list of the centre (84.2%) consisting of 36 drugs. The list contained 20 drugs with proprietary names of which six were fixed-dose combinations. The local drug list needs modification. The proportion of drugs prescribed by generic name was 49.5%. As per Kunin's criteria, 57.9% of the antibiotics used were appropriate. Interns often forget to write the diagnosis (43%), signs and symptoms (50.2%), dosages and frequency of treatment. The result of this baseline study may be useful in promoting the education necessary in order to achieve the objectives of good prescribing.


Increased expression of Bcl-xL and c-Myc is associated with transformation by Abelson murine leukemia virus.
Transformation mediated by the v-Abl oncoprotein, a tyrosine kinase encoded by the Abelson murine leukemia virus, is a multi-step process requiring genetic alterations in addition to expression of v-Abl. Loss of p53 or p19ARF was previously shown to be required for Abelson murine leukemia virus transformation of primary mouse embryonic fibroblasts (MEFs). By comparing gene expression patterns in primary p53-/- MEFs acutely infected with the v-Abl retrovirus, v-Abl-transformed MEF clones, and v-Abl-transformed MEF clones treated with Abl kinase inhibitor STI 571, we have identified additional genetic alterations associated with v-Abl transformation. Bcl-xL mRNA was elevated in three of five v-Abl-transformed MEF clones. In addition, elevated expression of c-Myc mRNA, caused either by c-myc gene amplification or by enhanced signaling via STAT3, was observed in five v-Abl-transformed MEF clones. The data suggest that increases in cell survival associated with Bcl-xL and increases in cell growth associated with c-Myc facilitate the transformation process dependent on constitutive mitogenic signaling by v-Abl.


Generation of Th1 immune responses to inactivated, gp120-depleted HIV-1 in mice with a dominant Th2 biased immune profile via immunostimulatory [correction of imunostimulatory] oligonucleotides--relevance to AIDS vaccines in developing countries.
Vaccination against HIV-1 of hosts with a dominant Th2 immune profile may fail to induce essential protective Th1 immune responses. By using Schistosoma-infected mice, with a pre-existent Th2 immune background, we demonstrate that oligodeoxynucleotides (ODN) containing unmethylated cytosine-phosphate-guanosine (CpG) immunostimulatory sequences co-administered with inactivated, gp120-depleted HIV-1 viral particles (HIV-1 immunogen) lead to potent Th1 anti-HIV-1 immune responses overcoming the Th2 bias. In contrast, Schistosoma-infected mice immunized with HIV-1 immunogen in incomplete Freund's adjuvant only, induced Th2 anti-HIV-1 immune responses. These findings strongly support the advisability of using CpG ODN as a Th1 inducing adjuvant when immunizing human populations with a strong pre-existent Th2 immune profile.


Long-term effectiveness of mailed nicotine replacement therapy: study protocol of a randomized controlled trial 5-year follow-up.
Our group recently completed a randomized controlled trial, evaluating the efficacy of providing 5 weeks of free nicotine replacement therapy (NRT; in the form of the nicotine patch) by expedited postal mail without behavioral assistance to regular adult smokers interested in receiving it. The findings revealed that mailed provision of nicotine patches resulted in more than a doubling of quit rates at a six-month follow-up compared to a no intervention control group. While this trial provided evidence for the effectiveness of mailed nicotine patches in promoting cessation, the findings speak only to the short term effectiveness of this approach. As relapse to smoking is known to occur beyond the 6 month period, it is important to evaluate whether the net benefit of NRT in naturalistic settings can be maintained long-term. The present study aims to perform a 5-year follow-up survey of participants in the original trial to evaluate the long-term effectiveness of mailed NRT. Trained interviewers will contact participants in the randomized controlled trial 5 years post-enrollment. A total of 924 participants will be eligible to be contacted. Interviewers will first assess participants' smoking status and their level of nicotine dependence. Participants reporting not currently smoking will be asked whether they have smoked tobacco, even a puff, in the last 30 days (primary outcome measure: 30-day point prevalence abstinence), past 6 months (secondary outcome measure: prolonged 6-month abstinence), and since the 8-week follow-up survey (secondary outcome measure: > 4 year continuous abstinence). Interviewers will be blind to experimental condition at the time the primary outcome measure will be assessed. It is hypothesized that participants who received nicotine patches at baseline will display significantly higher quit rates at the 5-year follow-up as compared to participants who did not receive nicotine patches at baseline. If the study finds that the mailed distribution of free NRT is effective at promoting long-term cessation, it would provide further evidence to move forward with policies designed to make NRT treatment readily and freely available to smokers who request it. ClinicalTrials.gov : NCT01429129 , Registered 2 September 2011; NCT03097445 , Registered 25 March 2017.


Cryosurgery in vasomotor rhinopathy: experimental histopathology.
Experimental cryosurgery of the nasal mucosa in normal guinea pigss and in animals with drug-induced vasomotor rhinopathy showed complete closure of the initial ulceration by a temporary atypical epithelium within 2 week. 3-4 weeks after cryotreatment, normal ciliated epithelium covered the whole area. Within 4-5 weeks, the last signs of inflammatory reaction dinappeared. The treatment resulted in a definitive reduction of mucosal thickness, and in a numerically significant loss of vessels and glandular acini. The hintopathological results thus agreed with the clinical objective of the treatment in vasomotor rhinopathy (reduction of the nasal resistance and diminution of rhinorrhea).


High-temperature electrocatalysis using thermophilic P450 CYP119: dehalogenation of CCl4 to CH4.
The use of a thermophilic cytochrome P450, CYP119, in electrocatalytic dehalogenations of C1 halocarbon solvents is studied. Temperature stable enzyme-modified electrodes were constructed using sol-gel and polymeric surfactant approaches. CYP119 deposited in a dimethyldidodecylammonium poly(p-styrene sulfonate) (DDAPSS) film has good retention of electrochemical activity up to 80 degrees C. At potentials approaching the FeII/I couple, the CYP119/DDAPSS films demonstrate high catalytic dehalogenations of the C1 chloromethanes CCl4, CHCl3, and CH2Cl2. Product analysis identified mixtures of sequentially dechlorinated products up to methane; no evidence for radical-coupled products was observed. The yield of methane from the CYP119-catalyzed reduction of CCl4 is increased 35-fold from 25 degrees C to 55 degrees C. In combination with the lack of C2 products, the facility of an overall eight-electron reductive dehalogenation suggests that the substrate is constrained within the protein during electrocatalytic turnover.


Successful treatment of myelodysplastic syndrome-induced pyoderma gangrenosum.
We report successful treatment of a refractory myelodysplastic syndrome-associated pyoderma gangrenosum with the combination of thalidomide and interferon-alpha2a in a single patient. A non-healing wound developed on a 40-year-old woman's left thumb after minor trauma. Massive ulcerovegetative lesions developed after reconstruction surgery. Histopathological examination of the bone marrow and cytogenetic studies revealed an atypical myeloproliferative/myelodysplastic syndrome. The skin lesions resolved dramatically after two months of thalidomide and interferon-alpha2a combination therapy and the haematological status improved.


Power laws of complex systems from extreme physical information.
Many complex systems obey allometric, or power, laws y=Y x(a) . Here y > or = 0 is the measured value of some system attribute a , Y> or =0 is a constant, and x is a stochastic variable. Remarkably, for many living systems the exponent a is limited to values n/4 , n=0, +/-1, +/-2.... Here x is the mass of a randomly selected creature in the population. These quarter-power laws hold for many attributes, such as pulse rate (n=-1) . Allometry has, in the past, been theoretically justified on a case-by-case basis. An ultimate goal is to find a common cause for allometry of all types and for both living and nonliving systems. The principle I-J=extremum of extreme physical information is found to provide such a cause. It describes the flow of Fisher information J-->I from an attribute value a on the cell level to its exterior observation y . Data y are formed via a system channel function y identical to f (x,a) , with f (x,a) to be found. Extremizing the difference I-J through variation of f (x,a) results in a general allometric law f (x,a) identical to y=Y x(a) . Darwinian evolution is presumed to cause a second extremization of I-J , now with respect to the choice of a . The solution is a=n/4 , n=0,+/-1,+/-2..., defining the particular powers of biological allometry. Under special circumstances, the model predicts that such biological systems are controlled by only two distinct intracellular information sources. These sources are conjectured to be cellular DNA and cellular transmembrane ion gradients.


Development of a Long-Term Sampling Method for Determination of NMHCs in Indoor Air.
Vapor intrusion is detrimental for indoor air quality. One of the most common sources of vapor intrusion is soil contaminated with petroleum hydrocarbons. To evaluate the long-term risk from individual exposure to hydrocarbons it is necessary to measure quantitively and reliably an average concentration level of individual pollutants on a monthly or yearly basis. Temporal variability of vapor intrusion from hydrocarbons poses a significant challenge to determination of average exposure and there is a need for reliable long-term integrative sampling. To this end, an analytical method for determination of 10 selected nonmethane hydrocarbons (NMHCs), including hexane, heptane, octane, decane, benzene, toluene, ethyl-benzene, m,p-xylene, o-xylene, and naphthalene, sampled on active triple-bed tubes filled with Carbograph 2, Carbograph 1, and Carboxen 1003 adsorbents was developed and validated. Extensive laboratory studies proved the absence of breakthrough at 50% HR and ambient temperature for experiments lasting up to 28 days and established a safe sampling time/volume of 20 days/114 L when sampling at a low flow rate of around 4 mL min-1. In addition, the developed method includes detailed uncertainty calculations for determination of concentrations. Finally, the method was tested by measuring NMHC concentrations in indoor air at a former industrial site during a 2-month-long field campaign in Lyon. The results of the field campaign suggest that 4-week integrated concentration measurements can be achieved by using active sampling on triple-bed tubes at 4.5 mL min-1.


Interleukin-1β causes excitotoxic neurodegeneration and multiple sclerosis disease progression by activating the apoptotic protein p53.
Understanding how inflammation causes neuronal damage is of paramount importance in multiple sclerosis (MS) and in other neurodegenerative diseases. Here we addressed the role of the apoptotic cascade in the synaptic abnormalities and neuronal loss caused by the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α) in brain tissues, and disease progression caused by inflammation in relapsing-remitting MS (RRMS) patients. The effect of IL-1β, but not of TNF-α, on glutamate-mediated excitatory postsynaptic currents was blocked by pifithrin-α (PFT), inhibitor of p53. The protein kinase C (PKC)/transient receptor potential vanilloid 1 (TRPV1) pathway was involved in IL-1β-p53 interaction at glutamatergic synapses, as pharmacological modulation of this inflammation-relevant molecular pathway affected PFT effects on the synaptic action of IL-1β. IL-1β-induced neuronal swelling was also blocked by PFT, and IL-1β increased the expression of p21, a canonical downstream target of activated p53.Consistent with these in vitro results, the Pro/Pro genotype of p53, associated with low efficiency of transcription of p53-regulated genes, abrogated the association between IL-1β cerebrospinal fluid (CSF) levels and disability progression in RRMS patients. The interaction between p53 and CSF IL-1β was also evaluated at the optical coherence tomography (OCT), showing that IL-1β-driven neurodegenerative damage, causing alterations of macular volume and of retinal nerve fibre layer thickness, was modulated by the p53 genotype. Inflammatory synaptopathy and neurodegeneration caused by IL-1β in RRMS patients involve the apoptotic cascade. Targeting IL-1β-p53 interaction might result in significant neuroprotection in MS.


Self-reported personality traits and disorders (DSM-IV) and risk of criminal recidivism: a prospective study.
Assessment and management of criminal offenders require valid methods to recognize personality psychopathology and other risk and protective factors for recidivism. We prospectively explored the association between dimensional and categorical measures of personality disorder (PD) measured with the DSM-IV and ICD-10 Personality Questionnaire (DIP-Q, Ottosson et al., 1995) and registered reconvictions in adult offenders. One hundred and sixty-eight offenders consecutively referred for pre-sentencing forensic psychiatric evaluation in Sweden during 1995-1996 completed DIP-Q self-reports. The subjects received different types of sanctions and were followed for an average of 36 months after release from prison, discharge from a forensic psychiatric hospital, or onset of nondetaining sentences. Age-adjusted odds ratios revealed a 4.8 times higher risk for any recidivism and a 3.7 times higher risk for violent recidivism among subjects whose self-reports suggested a categorical diagnosis of antisocial PD as compared to offenders without antisocial PD. The remaining nine categorical DSM-IV PD diagnoses were not significantly related to recidivism. In dimensional analyses, each additional antisocial and schizoid PD symptom endorsed by participants at baseline increased the risk for violent reoffending. Our results suggest a relationship between self-reported behavioral instability and interpersonal dysfunction captured primarily by DSM-IV antisocial and schizoid PD constructs, and criminal re-offending also in a multi-problem sample of identified offenders.


Influence of Genetic Variations in Selenoprotein Genes on the Pattern of Gene Expression after Supplementation with Brazil Nuts.
Selenium (Se) is an essential micronutrient for human health. Its beneficial effects are exerted by selenoproteins, which can be quantified in blood and used as molecular biomarkers of Se status. We hypothesize that the presence of genetic polymorphisms in selenoprotein genes may: (1) influence the gene expression of specific selenoproteins and (2) influence the pattern of global gene expression after Brazil nut supplementation. The study was conducted with 130 healthy volunteers in Sao Paulo, Brazil, who consumed one Brazil nut (300 μg/Se) a day for eight weeks. Gene expression of GPX1 and SELENOP and genotyping were measured by real-time PCR using TaqMan Assays. Global gene expression was assessed by microarray using Illumina HumanHT-12 v4 BeadChips. Brazil nut supplementation significantly increased GPX1 mRNA expression only in subjects with CC genotype at rs1050450 (p < 0.05). SELENOP mRNA expression was significantly higher in A-carriers at rs7579 either before or after supplementation (p < 0.05). Genotype for rs713041 in GPX4 affected the pattern of blood cell global gene expression. Genetic variations in selenoprotein genes modulated both GPX1 and SELENOP selenoprotein gene expression and global gene expression in response to Brazil nut supplementation.


[Recombinant human TSH use in differentiated thyroid cancer].
Traditionally, the immediate treatment of patients with differentiated thyroid carcinoma (DTC) after total thyroidectomy (TT) is thyroid remnant ablation (TRA) with 131I, during hypothyroidism. Late follow-up of DCT includes suppressive doses of T4, serial measurements of thyroglobulin (Tg), whole body scan (WBS) with 131I and cervical ultrasound (US). In the last years, TRA with the aid of recombinant human TSH (rhTSH) has shown not only to avoid symptoms of hypothyroidism and a lower quality of life, but also to have the same efficacy as TRA during endogenous TSH elevation. Stimulated Tg with endogenous or exogenous TSH, 9 to 12 months after the initial treatment of DTC, associated with cervical US, is able to identify low-risk patients virtually cured of their disease, in whom TSH suppression does not need to be so strict, avoiding the heart and bone complications of prolonged exogenous thyrotoxicosis. Finally, in spite of the absence of randomized studies designed to evaluate the role of rhTSH in metastatic DTC disease, results of the combined treatment of rhTSH and 131I show a clinical benefit in the majority of treated patients.


Specimen holders for simultaneous critical point drying of multiple biological specimens.
Specimen holders were developed for simultaneous critical point drying of multiple specimens of monolayer cell cultures grown on Leighton tube glass cover slips or for specimens of cells collected on silver or cellulose membrane filters. The use of these multiple specimen holders makes it possible to process several specimens in parallel and thus significantly reduce the time required for handling large numbers of samples and also eliminate the possible variations that occur in processing individual samples one at a time in series.


[The relation of speech to the right and left cerebral hemispheres].
Verbal speech functions are localized in right-handed subjects nearly exclusively and in left-handed ones mostly in the left hemisphere. Much information on these functions has been obtained by studying patients affected with spontaneous damages, as well as after hemispherectomy, after severing the corpus callosum, and during electric stimulation of the brain in neurosurgical procedures. In the presylvian region of the hemisphere dominant for speech, a region for the production and identification of speech was found, surrounded by an area for shortterm verbal memory. The predominance of the right ear in recognizing verbal stimuli, established by the dichotic test, applies to the population rather than to the individual. The substance of verbal dominance of the left hemisphere lies in the prevalence of its capacity to distinguish rapid acoustic sequences and to produce them. Observations made on deaf-mute patients with sign language have demonstrated that humans possess a genetically determined ability to develop speech, regardless the modality. Speech functions of the right hemisphere concern mostly nonverbal prosodic components of speech.


Preoperative High Neutrophil-to-Lymphocyte Ratio Is Associated with High-grade Bladder Cancer.
To evaluate the correlation between the neutrophil-to-lymphocyte ratio (NLR) and histopathological characteristics of bladder cancer. A retrospective analysis was performed on a cohort of patients (n=302) who were diagnosed with bladder cancer and underwent transurethral resection of bladder tumor or cystectomy between 2009 and 2016. The pathological outcomes were compared between patients with low NLR and those with high NLR with a cut-off value of 2.5, and a logistic regression analysis was performed to find potential predictors of pathological tumor outcomes. Patients with high-grade disease had significantly higher NLRs compared to those with low-grade disease (median NLR=4.42 vs. 3.42, p<0.001). Univariate analysis suggested that age, neutrophil count and NLR, as a continuous or binary variable, were significantly associated with high-grade disease. Multivariate analysis suggested that age and NLR, as a continuous variable, were predictors of pathologically high-grade disease. Preoperative NLR was found to be associated with pathological tumor grading, but was not associated with pathological tumor staging in patients with bladder cancer.


Quality of life three months post‑stroke among stroke patients and their caregivers in a single center study from Romania during the COVID‑19 pandemic: A prospective study.
The aim of the present study was to determine the health-related quality of life of stroke patients and their caregivers during the fifth wave of the COVID-19 pandemic. A total of 70 patients who had been diagnosed with stroke between October 2021 and March 2022 and 70 caregivers were included in the present study. A prospective follow-up study assessing the quality of life at baseline was conducted after 3 months for both patients and their caregivers. A linear regression analysis was performed to evaluate potential associations between quality of life and assessed factors. The results revealed that age, sex, employment status, hospitalization period, type of stroke, Barthel index for activities of daily living (ADL) and discharge Modified Rankin Scale (mRS), were significant determinants of the 90-day Health-Related Quality of Life (HRQoL). An important clinical change in the QoL score was estimated for both post-stroke patients and their caregivers. The decrease of the HRQoL of patients was statistically influenced by a higher value of ADL (P=0.014), whereas, in the case of their caregivers, the decrease of HRQoL was primarily influenced by the QoL of patients after 3 months (P=0.043). The present study identified some important key factors with direct consequences on HRQoL regarding stroke survivors and their caregivers.


Fall in thyroid stimulating hormone (TSH) may be an early marker of ipilimumab-induced hypophysitis.
Hypophysitis develops in up to 19% of melanoma patients treated with ipilimumab, a cytotoxic T-lymphocyte antigen-4 antibody. Early detection may avert life-threatening hypopituitarism. We aimed to assess the incidence of ipilimumab-induced hypophysitis (IH) at a quaternary melanoma referral centre, and to determine whether cortisol or thyroid stimulating hormone (TSH) monitoring could predict IH onset. We performed a retrospective cohort study of ipilimumab-treated patients at a quaternary melanoma referral centre in Australia. The inclusion criteria were patients with metastatic or unresectable melanoma treated with ipilimumab monotherapy, and cortisol and TSH measurements prior to ≥ 2 infusions. The main outcomes were IH incidence and TSH and cortisol patterns in patients who did and did not develop IH. Of 78 ipilimumab-treated patients, 46 met the study criteria and 9/46 (20%) developed IH at a median duration of 13.0 weeks (range 7.7-18.1) following ipilimumab initiation. All patients whose TSH fell ≥ 80% compared to baseline developed IH, and, in 5/9 patients with IH, TSH fell prior to cortisol fall and IH diagnosis. Pre-cycle-4 TSH was significantly lower in those who developed IH (0.31 vs. 1.73 mIU/L, P = 0.006). TSH fall was detected at a median time of 9.2 (range 7.7-16.4) weeks after commencing ipilimumab, and a median of 3.6 (range of - 1.4 to 9.7) weeks before IH diagnosis. There was no difference in TSH between the groups before cycles 1-3 or in cortisol before cycles 1-4. TSH fall ≥ 80% may be an early marker of IH. Serial TSH measurement during ipilimumab therapy may be an inexpensive tool to expedite IH diagnosis.


Plant responses to insect herbivory: interactions between photosynthesis, reactive oxygen species and hormonal signalling pathways.
Under herbivore attack plants mount a defence response characterized by the accumulation of secondary metabolites and inhibitory proteins. Significant changes are observed in the transcriptional profiles of genes encoding enzymes of primary metabolism. Such changes have often been interpreted in terms of a requirement for an increased investment of resources to 'fuel' the synthesis of secondary metabolites. While enhanced secondary metabolism undoubtedly exerts an influence on primary metabolism, accumulating evidence suggests that rather than stimulating photosynthesis insect herbivory reduces photosynthetic carbon fixation and this response occurs by a re-programming of gene expression. Within this context, reactive oxygen species (ROS) and reductant/oxidant (redox) signalling play a central role. Accumulating evidence suggests that ROS signalling pathways are closely interwoven with hormone-signalling pathways in plant-insect interactions. Here we consider how insect infestation impacts on the stress signalling network through effects on ROS and cellular redox metabolism with particular emphasis on the roles of ROS in the plant responses to phloem-feeding insects.


Nonextensive boltzmann equation and hadronization.
We present a novel nonextensive generalization of the Boltzmann equation. We investigate the evolution of the one-particle distribution in this framework. The stationary solution is exponential in a nonlinear function of the original energy. The total energy is composed using a general, associative nonextensive rule. We propose that for describing the hadronization of quark matter such rules may apply.


KidzMed e-learning to upskill student pharmacists to teach pill swallowing to children.
Appropriate medication use is essential in ensuring optimal pharmacotherapeutic outcomes. It is mistakenly assumed that adults can swallow solid oral dosage forms (SODFs, e.g. tablets/capsules colloquially referred to as 'pills'), without difficulty and that children cannot. KidzMed is a 'pill swallowing' training programme designed to teach effective SODF use in patients of all ages. It may be utilised by healthcare professionals to assist patients taking SODFs. E-learning was essential for training during COVID pandemic to reduce viral transmission. The aim of this study was to explore UK student pharmacists views of e-learning to support swallowing solid oral dosage forms. This study used pre- and post-intervention online surveys on Microsoft Forms to evaluate self-directed eLearning about pill swallowing on MPharm programmes at three UK Universities using a 13-item survey. A combination of five-point Likert Scales and free-text items were used. The eLearning was available via the virtual learning environment at the University and embedded within existing curriculum. Descriptive statistical analysis was used to explore responses. In total, 113 of 340 (33%) students completed the survey. Seventy-eight percent (n = 65) reported the eLearning would enable them to teach adults and children to swallow SODFs successfully. Learners either agreed or strongly agreed that they felt comfortable to teach patients (95%, n = 62/113) and parents or carers (94%, n = 60) to swallow medications having completed the e-learning. Student pharmacists generally found eLearning as an acceptable way to reflect on their own experiences of 'pill' swallowing and how to support patients to swallow SODFs. The KidzMed eLearning was well received by student pharmacists. Further work is needed to explore whether skills translates into real life application in the clinical settings.


Quantifying reaction kinetics of the non-enzymatic decarboxylation of pyruvate and production of peroxymonocarbonate with hyperpolarized 13C-NMR.
The transient nature of intermediate states in chemical reactions has made their detailed investigation difficult. In this study, we demonstrate the utility of hyperpolarized 13C-NMR to directly observe and quantify the kinetics of the intermediate compound in the non-enzymatic decarboxylation of pyruvate via H2O2 with time resolutions of <1 s. Reactants were sequentially added to a reaction vessel within a 9.4 T NMR magnet while continuously acquiring spectra with a low flip angle, producing the first direct observation at room temperature of the previously proposed reaction intermediate, 2-hydroperoxy-2-hydroxypropanoate. We also performed a series of NMR experiments to determine the identity of a previously unidentified peak, which was found to be peroxymonocarbonate, the product of the side reaction between HCO3-/CO2 and H2O2/OOH-. Using the information obtained from these experiments, we developed a kinetic model which fully describes the mechanism of reaction and can be fit to experimental data to simultaneously determine multiple kinetic rate constants over several orders of magnitude. We also discuss the application of this reaction to the production of hyperpolarized bicarbonate for pH imaging experiments. This study presents a template for the use of hyperpolarized 13C-NMR to study the kinetics and reaction mechanisms of innumerable organic reactions which involve polarizable substrates.


Monitoring Tribolium castaneum (Coleoptera: Tenebrionidae) in pilot-scale warehouses treated with residual applications of (S)-hydroprene and cyfluthrin.
Pilot-scale warehouses, artificially infested with all life stages of Tribolium castaneum (Herbst), were used to evaluate the efficacy of two contact insecticides, (S)-hydroprene and cyfluthrin, and to determine the effect of insecticide treatments on insect captures in food- and pheromone-baited pitfall traps. Two application strategies were compared; insecticides were applied at the labeled rate either around the inside perimeter of the warehouse or in a band around the base of shelf units containing discrete food patches (10 g of wheat flour) infested with T. castaneum. Insect populations were assessed weekly for 6 wk by recording number of dead adults on the warehouse floor; number of larvae and adults captured in pitfall traps; and number of larvae, pupae, and adults recovered from food patch samples. There were significantly more dead adults in warehouses treated with cyfluthrin than with (S)-hydroprene or water (control treatment). However, food patch samples showed no detectable differences in quantity of larvae, pupae, or adults among any treatments. Pitfall traps detected fewer larvae starting the fourth week of the study in the warehouses treated with cyfluthrin around the shelf perimeter. Rate of larval capture in traps increased overall with increasing larval populations, but it was more pronounced in traps located closer to the food patches. Number of adults captured in pitfall traps reflected adult mortality in cyfluthrin-treated warehouses. Capture of larvae and adults was greater near the source of the infestation than elsewhere in the warehouse, suggesting that trapping data should be considered when precision targeting insecticide applications in the field.


[How much quality loss can and will society afford?].
In Germany, there is an ever increasing gap between the legitimate claim to quality treatment and current health care reality. While the Republic of Germany still is among the world's best as regards the number of insured persons, health care expenditure and its share in gross national product, medical care has declined from top to medium quality. Underuse, overuse and misuse of health care resources have become noticeable, and patients are beginning to lose confidence in our healthcare system. Examples of deficit areas include the undersupply of care for many patients in the nursing sector, the life-threatening implications of trivialising diseases like sleep apnoea and the care of schizophrenic patients that is still lagging behind international standard. For many years German healthcare policy has only aimed at achieving cost containment, without simultaneously introducing drastic reforms to put an end to mismanagement. So far all attempts at reforming our healthcare system have only led to increased costs for the paying patients. In the face of this development the patients' demand for more information on healthcare system issues is rising and--due to better access to various novel information sources on the broad range of healthcare possibilities also--they are calling for improved medical care. The special focus is that modern, quality-oriented medicine will ultimately turn out to be the more efficient and cost-effective medicine.


NDRG1, a growth and cancer related gene: regulation of gene expression and function in normal and disease states.
N-myc downstream-regulated gene 1 (NDRG1) is an intracellular protein that is induced under a wide variety of stress and cell growth-regulatory conditions. NDRG1 is up-regulated by cell differentiation signals in various cancer cell lines and suppresses tumor metastasis. Despite its specific role in the molecular cause of Charcot-Marie-Tooth type 4D disease, there has been more interest in the gene as a marker of tumor progression and enhancer of cellular differentiation. Because it is strongly up-regulated under hypoxic conditions, and this condition is prevalent in solid tumors, its regulation is somewhat complex, governed by hypoxia-inducible factor 1 alpha (HIF-1alpha)- and p53-dependent pathways, as well as its namesake, neuroblastoma-derived myelocytomatosis, and probably many other factors, at the transcriptional and translational levels, and through mRNA stability. We survey the data for clues to the NDRG1 gene's mechanism and for indications that the NDRG1 gene may be an efficient diagnostic tool and therapy in many types of cancers.


Evidence for glutamate as the olfactory receptor cell neurotransmitter.
1. Synaptic transmission between olfactory receptor neurons and mitral/tufted cells was examined using a whole-cell recording technique in a hemisected preparation of the turtle olfactory bulb. To determine the olfactory receptor neuron transmitter, we isolated components of the synaptic response of mitral/tufted cells to olfactory nerve stimulation using postsynaptic receptor antagonists. 2. Low-intensity stimulation of the olfactory nerve evoked monosynaptic excitatory postsynaptic potentials in mitral/tufted cells that consisted of a rapid and prolonged depolarization with little contribution from other bulb neurons. The exogenous application of glutamate mimicked the response of mitral/tufted cells to olfactory nerve stimulation. 3. Olfactory nerve stimulation evoked in mitral/tufted cells a two component response that was reversibly blocked by glutamate receptor antagonists. The first, a rapid depolarization of short duration, was sensitive to the non-N-methyl-D-aspartate (NMDA) receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX); the second, a depolarization of slower onset but longer duration, was sensitive to the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5). When DNQX and AP5 were both present the postsynaptic response was completely abolished. These results strongly support the notion that glutamate is the neurotransmitter at the olfactory nerve to mitral/tufted cell synapse.


Application of whole-cell DNA restriction endonuclease profiles to the epidemiology of Clostridium difficile-induced diarrhea.
Two patients in one hospital room acquired pseudomembranous colitis, one shortly after the other. The DNA restriction patterns of isolates from the patients and of four isolates from the environment were indistinguishable from one another and differed from isolates of other patients. Restriction endonuclease digest analysis appears to be a useful method for studying the epidemiology of Clostridium difficile.


A Deep Learning Model with Signal Decomposition and Informer Network for Equipment Vibration Trend Prediction.
Accurate equipment operation trend prediction plays an important role in ensuring the safe operation of equipment and reducing maintenance costs. Therefore, monitoring the equipment vibration and predicting the time series of the vibration trend is one of the effective means to prevent equipment failures. In order to reduce the error of equipment operation trend prediction, this paper proposes a method for equipment operation trend prediction based on a combination of signal decomposition and an Informer prediction model. Aiming at the problem of high noise in vibration signals, which makes it difficult to obtain intrinsic characteristics when directly using raw data for prediction, the original signal is decomposed once using the variational mode decomposition (VMD) algorithm optimized by the improved sparrow search algorithm (ISSA) to obtain the intrinsic mode function (IMF) for different frequencies and calculate the fuzzy entropy. The improved adaptive white noise complete set empirical mode decomposition (ICEEMDAN) is used to decompose the components with the largest fuzzy entropy to obtain a series of intrinsic mode components, fully combining the advantages of the Informer model in processing long time series, and predict equipment operation trend data. Input all subsequences into the Informer model and reconstruct the results to obtain the predicted results. The experimental results indicate that the proposed method can effectively improve the accuracy of equipment operation trend prediction compared to other models.


Automated SEM/EDS analysis of airbag residue. II: Airbag residue as a source of percussion primer residue particles.
Automated scanning electron microscopy with energy dispersive spectroscopy has been used to analyze airbag residue particles. Analysis of airbag residue from some passenger side airbags revealed some residue particles which are consistent with gunshot residue (GSR) samples. The source of these particles was determined to be percussion primers used to initiate the chemical reaction for deployment. This article identifies some vehicles which contain this type of airbag and demonstrates the types of particles which could be misidentified as being GSR. The low numbers of GSR particles in among the large particle populations of zirconium and/or copper-cobalt particles, which are clearly airbag residue, allow the trained analysts to distinguish the correct source of this residue. Particles containing high aluminum levels, elevated levels of allowable elements in GSR particles, or the presence of elements that are rare in GSR particles stand out as indications that the particles are not GSR in origin. This study serves as a guide to analysts who perform particle analysis in forensic investigations.


Cystobactamids: myxobacterial topoisomerase inhibitors exhibiting potent antibacterial activity.
The development of new antibiotics faces a severe crisis inter alia owing to a lack of innovative chemical scaffolds with activities against Gram-negative and multiresistant pathogens. Herein, we report highly potent novel antibacterial compounds, the myxobacteria-derived cystobactamids 1-3, which were isolated from Cystobacter sp. and show minimum inhibitory concentrations in the low μg mL(-1) range. We describe the isolation and structure elucidation of three congeners as well as the identification and annotation of their biosynthetic gene cluster. By studying the self-resistance mechanism in the natural producer organism, the molecular targets were identified as bacterial type IIa topoisomerases. As quinolones are largely exhausted as a template for new type II topoisomerase inhibitors, the cystobactamids offer exciting alternatives to generate novel antibiotics using medicinal chemistry and biosynthetic engineering.


The effects of inspiratory diaphragm breathing exercise and expiratory pursed-lip breathing exercise on chronic stroke patients' respiratory muscle activation.
[Purpose] The purpose of this study is to examine the effects of inspiratory diaphragm breathing exercise and expiratory pursed-lip breathing exercise on chronic stroke patients' respiratory muscle activation. [Subjects and Methods] All experimental subjects performed exercises five times per week for four weeks. Thirty chronic stroke patients were randomly assign to an experimental group of 15 patients and a control group of 15 patients. The experimental group underwent exercises consisting of basic exercise treatment for 15 minutes and inspiratory diaphragm breathing exercise and expiratory pursed-lip breathing exercise for 15 minutes and the control group underwent exercises consisting of basic exercise treatment for 15 minutes and auto-med exercise for 15 minutes. The activation levels of respiratory muscles were measured before and after the experiment using MP 150WSW to obtain the results of the experiment. [Results] In the present study, when the pulmonary functions of the experimental group and the control group before and after the experiment were compared, whereas the experimental group showed significant differences in all sections. In the verification of intergroup differences between the experimental group and the control group before and after the experiment. [Conclusion] The respiratory rehabilitation exercise is considered to be capable of inducing positive effects on stroke patients' respiratory muscles through diaphragm breathing exercise and lip puckering breathing exercise.


Surface Preparation for Single-Molecule Chemistry.
Immobilization procedures, intended to enable prolonged observation of single molecules by fluorescence microscopy, may generate heterogeneous microenvironments, thus inducing heterogeneity in the molecular behavior. On that account, we propose a straightforward surface preparation procedure for studying chemical reactions on the single-molecule level. Sensor fluorophores were developed, which exhibit dual-emissive characteristics in a homogeneously catalyzed showcase reaction. These molecules undergo a shift of fluorescence wavelength of about 100 nm upon Pd(0)-induced deallylation in the Tsuji-Trost reaction, allowing for separate visualization of the starting material and product. Whereas a simultaneous immobilization of dye and inert silane leads to strongly polydisperse reaction kinetics, a consecutive immobilization routine with deposition of dye molecules as the last step provides substrates underlying the kinetics of ensemble experiments. Also, the found kinetics are unaffected by the chemical variation of inert silanes, nearly uniform, and therefore well reproducible. Additional parameters like photostability, signal-to-noise ratio, dye-molecule density, and spatial distribution of dye molecules are, as well, hardly affected by surface modification in the successive immobilization scheme.