Proliferating cell nuclear antigen (PCNA) and human malignant tumor nucleolar antigens (HMTNA) in nucleoli of human hematological malignancies.
Lymphoma (Lymphocytic non-Hodgkin's malignant lymphoma) and leukemic (chronic lymphocytic, acute and chronic myeloid, myelomonocytic leukemia) cells were studied by indirect immunofluorescence to evaluate the presence of proliferating cell nuclear antigen (PCNA) and human malignant tumor nuclear antigen (HMTNA) in their nucleoli. Most cells in lymph node smears of lymphocytic non-Hodgkin's malignant lymphoma (NHML) developed a bright nucleolar fluorescence with HMTNA antibodies. PCNA was detected in nucleoli of a limited number of cells which apparently represent the proliferating cell population in these lymphomas. Similarly, in the bone marrow smears of patients with chronic lymphocytic leukemia most cells possessed a nucleolar fluorescence for HMTNA and PCNA was present in nucleoli of a limited number of cells. In the bone marrow smears of patients with myeloid or myelomonocytic leukemias most blastic or monocytoid cells also developed a bright nucleolar fluorescence with HMTNA antibodies and PCNA was present only in a small percentage of these cells. Leukemic cells with PCNA in their nucleoli like thekhuntigen might represent a proliferating cell population in late G1-early S phase.


Carotid artery longitudinal wall motion alterations associated with metabolic syndrome and insulin resistance.
Our objective was to study relationships between the new biomarker of vascular health, carotid artery longitudinal wall motion (CALM) and metabolic syndrome (MetS). Carotid ultrasound and assessment of MetS and its components were performed with 281 subjects aged 30-45 years. In the longitudinal motion analysis, the amplitude of motion and the antegrade-oriented and retrograde-oriented components of motion between the intima-media complex and adventitial layer of the common carotid artery wall were assessed. Metabolic syndrome, according to the harmonized criteria, was detected in 53 subjects (19%). MetS was significantly associated with increased antegrade and decreased retrograde longitudinal motion in the carotid artery wall. Augmented antegrade amplitude of longitudinal motion was associated with obesity (β = 0.149, p < .05) and low HDL cholesterol (β = 0.177, p < .01). Attenuated retrograde amplitude of longitudinal motion was associated with hypertension (β = -0.156, p < .05), obesity (β = -0.138, p < .05) and hyperinsulinaemia (β = -0.158, p < .01). Moreover, insulin resistance (homeostasis model assessment index above 2.44) was associated with adverse changes in CALM. Metabolic syndrome and insulin resistance were associated with alterations in CALM. In particular, hypertension, obesity and hyperinsulinaemia were associated with reduced total peak-to-peak amplitude as well as increased antegrade and reduced retrograde amplitudes, all of which might be markers of unfavourable vascular health.


Trimazosin for the treatment of hypertensive patients failing to respond to thiazides.
In a double-blind study of two populations-one in Birmingham, Alabama, the other in Encinitas, California-a total of 32 hypertensive patients whose blood pressure was not controlled by thiazides alone were evaluated for their response to trimazosin. Patients showing a persistent diastolic blood pressure above 90 mm Hg while receiving 2 mg polythiazide once a day (at Birmingham) or 50 mg hydrochlorothiazide twice a day (at Encinitas) during a baseline 4-week period were randomly assigned to trimazosin and placebo groups. At both clinics, patients had a greater blood pressure response to trimazosin than to placebo in both supine and standing positions. When the data were pooled, the change in supine blood pressure (systolic/diastolic) between the average baseline values and the double-blind period was more than twofold greater for the trimazosin group, a decrease of 12.3/10.9 mm Hg (p less than 0.001). A lesser decrease of 5.4/5.4 mm Hg occurred in the placebo group, significant only for the diastolic pressure (p less than 0.01). Comparative differences between the trimazosin and the placebo groups were more marked for the standing blood pressures, -11.7/-10.0 mm Hg (p less than 0.0001) vs no significant change, +2.3/-2.8 mm Hg, respectively. Little change occurred in the patients' heart rates in either position in either treatment group. Adverse reactions were not clinically important and occurred in about half of the patients in the trimazosin and placebo groups. Therapy was not discontinued in either group because of adverse reactions.(ABSTRACT TRUNCATED AT 250 WORDS)


Visualizing endoderm cell populations and their dynamics in the mouse embryo with a Hex-tdTomato reporter.
Live imaging is the requisite tool for studying cell behaviors driving embryonic development and tissue formation. Genetically encoded reporters expressed under cell type-specific cis-regulatory elements that drive fluorescent protein expression at sufficient levels for visualization in living specimens have become indispensable for these studies. Increasingly dual-color (red-green) imaging is used for studying the coordinate behaviors of two cell populations of interest, identifying and characterizing subsets within broader cell populations or subcellular features. Many reporters have been generated using green fluorescent protein (GFP) due to its brightness and developmental neutrality. To compliment the large cohort of available GFP reporters that label cellular populations in early mouse embryos, we have generated a red fluorescent protein (RFP)-based transgenic reporter using the red fluorescent tdTomato protein driven by cis-regulatory elements from the mouse Hex locus. The Hex-tdTomato reporter predominantly labels endodermal cells. It is a bright RFP-based reporter of the distal visceral endoderm (DVE)/anterior visceral endoderm (AVE), a migratory population within the early post-implantation embryo. It also labels cells of the definitive endoderm (DE), which emerges at gastrulation. Dual-color visualization of these different early endodermal populations will provide a detailed understanding of the cellular behaviors driving key morphogenetic events involving the endoderm.


Analysis of cell proliferation, senescence, and cell death in zebrafish embryos.
Proper control of cell proliferation is critical for normal development, growth, differentiation, and tissue homeostasis. Dysregulation of cell division and cell death underlies almost all cancers, and contributes to the pathology of birth defects and degenerative diseases. The zebrafish has proved to be an excellent system for elucidating the roles of the cell cycle in normal development, and ways in which dysregulation of cell proliferation contributes to disease. This chapter describes the methods for studying the cell cycle in zebrafish embryos, including protocols to examine cell proliferation, DNA damage, senescence, and cell death.


Dissociation of lutropin-induced loss of testicular lutropin receptors and lutropin-induced desensitization of testosterone synthesis.
The relationship between changes in testicular lutropin receptors, as measured by specific binding of 125I-labeled human chorionic gonadotropin, and testosterone synthesis in response to lutropin (testicular responsiveness) was studied in intact and hypophysectomized rats. Administration of a single 200-microgram dose of ovine lutropin to intact rats results at 3 days in a 58% decrease in lutropin receptors associated with a parallel decrease in testicular responsiveness. A single 30-microgram dose of lutropin to intact rats resulted in a comparable decrease in lutropin receptors with a transient increase in testicular responsiveness. Rats receiving twice-daily injections of 15 microgram lutropin for 10 days exhibited a 48% decrease in lutropin receptors by day 3 which persisted during the 10-day treatment period, but was accompanied by a progressive increase in testicular responsiveness to lutropin. Hypophysectomy resulted in an 80% loss of receptors and a 72% loss in responsiveness 7 days after surgery. Daily treatment with lutropin initiated immediately following surgery resulted in a further dose-dependent decrease in lutropin receptors and a dose-dependent increase in testicular responsiveness. Loss of lutropin receptors was not due to occupancy of the receptor by exogenous lutropin. These studies demonstrate a dissociation between the negative regulation of lutropin receptors and testicular responsiveness to lutropin. Furthermore, the studies in hypophysectomized rats indicate that lutropin is the only hormone essential for maintenance of steroidogenesis and that this is independent of lutropin receptor concentration.


Hans Driesch and the problems of "normal psychology". Rereading his Crisis in Psychology (1925).
In 1925, the German biologist and philosopher Hans Driesch published a booklet entitled The Crisis in Psychology. It was originally published in English and was based on lectures given at various universities in China, Japan and the USA. The "crisis" in psychology of that time, in Driesch's opinion, lies in the necessity to decide about "the road which psychology is to follow in the future". This necessity refers to five "critical points", namely (1) to develop the theory of psychic elements to a theory of meaning by phenomenological analysis, (2) the overcoming of association theory, (3) to acknowledge that the unconscious is a fact and a "normal" aspect of mental life, (4) to reject "psychomechanical parallelism" or any other epiphenomenalistic solution of the mind-body problem, and (5) the extension of psychical research to new facts as described by parapsychology, for instance. Driesch saw close parallels between the development of modern psychology and that of biology, namely in a theoretical shift from "sum-concepts" like association and mechanics, to "totality-concepts" like soul and entelechy. The German translation of 1926 was entitled Grundprobleme der Psychologie (Fundamental Problems of Psychology) while "the crisis in psychology" forms just the subtitle of this book. This underlines that Driesch's argumentation--in contrast to that of Buehler--dealt with ontological questions rather than with paradigms.


Altered iron metabolism, transferrin receptor 1 and ferritin in patients with colon cancer.
In this study, the level and distribution of transferrin receptor 1 (TfR1) and ferritin in colorectal carcinoma and in normal colon epithelium has been determined relative to the tumor stage and iron status of patients using immunohistochemical staining methods. While the majority of carcinoma patients were anemic, no relationship between the level of colon tissue ferritin and TfR1 and the systemic parameters of iron metabolism was evident. Furthermore, no association between ferritin content and the grade of colorectal carcinoma was observed. However, a relationship between the expression of TfR1 and the grade of colorectal carcinoma was observed. In this case high expression of TfR1 was found in colorectal carcinoma samples of Dukes A or B grade, and well differentiated colorectal carcinoma cells. In comparison, weak or no expression of TfR1 was observed in carcinoma samples of Dukes C or D grade with poorly differentiated cells and in carcinoma samples that had lymph node infiltration and distant metastasis.


Pharmacokinetics of high-dose pentobarbital in severe head trauma.
High-dose pentobarbital infusion has been advocated as an effective adjunct in controlling persistent intracranial hypertension after severe head trauma in patients refractory to conventional therapy. Pentobarbital disposition was assessed in 10 adults with severe nonpenetrating head injury after an intravenous loading dose of sodium pentobarbital, 10 mg/kg, infused over 1 hour, followed by a continuous infusion at 0.5 to 3.0 mg/kg/hr provided the cerebral perfusion pressure remained greater than 50 torr. Pharmacokinetic parameters of volume of distribution at steady state (Vss), total body clearance (CL), and t1/2 for the patients with trauma were statistically compared with similar estimates reported for seven adult subjects without head injury. On discontinuation of the pentobarbital infusion, serum concentrations in the patients followed a monoexponential decline with a mean (+/- SD) t1/2 and Vss that were significantly less than values reported for the control subjects (15.6 +/- 3.9 vs. 22.3 +/- 4.0 hours and 44.0 +/- 11.7 vs. 63.4 +/- 15.2 L, respectively). However, there was no significant difference between the mean pentobarbital CL of the patients (2.0 +/- 0.7 L/hr) and the subjects (2.0 +/- 0.4 L/hr). To our knowledge this is the first report on the disposition, elimination, and intrasubject variability of high-dose pentobarbital infusion in adult patients with head trauma.


Protective effect of interleukin-36 receptor antagonist on liver injury induced by concanavalin A in mice.
Interleukin-36 receptor antagonist (IL-36Ra) is a new member of the IL-1 family that exhibits anti-inflammatory activity in a variety of inflammatory and immune diseases. Our purpose was to determine the effect of IL-36Ra on liver injury in a mouse hepatitis model induced by concanavalin A (ConA). Mice were treated with IL-36Ra DNA or pcDNA3.1 control plasmid using a hydrodynamic gene delivery approach. Our data reveal that treatment with IL-36Ra decreased liver inflammation and serum level of aminotransferases. Furthermore, IL-36Ra reduced ConA-induced pro-inflammatory cytokines (interferon-γ, tumor necrosis factor-α, and IL-17A) production when compared to control plasmid. Our results demonstrated that IL-36Ra is a critical protector against ConA-induced liver injury.


A comparison of insulin doses for treatment of hyperkalaemia in intensive care unit patients with renal insufficiency.
Hyperkalaemia is a complication in patients with chronic kidney disease or acute kidney injury and occurs frequently in the intensive care unit. One treatment approach includes intravenous (IV) insulin to shift potassium intracellularly. The primary outcome was hypoglycaemia (blood glucose <70 mg/dL) after insulin administration. Secondary outcomes included change in serum potassium levels and incidence of severe hypoglycaemia. This was a single-centre, retrospective study evaluating critically ill adult patients with chronic kidney disease stage III-V, end-stage renal disease, or acute kidney injury who received IV insulin for treatment of hyperkalaemia from March 2008 to September 2018. Patients were divided into two insulin-dosing regimen groups: 5 units or 10 units. Of the 174 patients included, hypoglycaemia after insulin administration occurred in eight of 87 patients (9.2%) in the 5-unit group and 17 of 87 patients (19.5%) in the 10-unit group (p = 0.052). There was no difference in rates of severe hypoglycaemia or change in serum potassium levels. In critically ill patients requiring treatment for hyperkalaemia, a lower dose of IV insulin does not result in lower statistically significant rates of hypoglycaemia. However, lower insulin doses provide a similar potassium-lowering effect and cause a meaningful decrease in hypoglycaemic episodes. Intensive care unit providers may consider 5 units of IV insulin over 10 units although further larger controlled studies are needed.


The effect of hessian and straw as nesting materials on sow behaviour and piglet survival and growth to weaning.
Sows are strongly driven to build a nest prior to farrowing, and the performance of this behaviour is linked to the environment in which the animal is housed. The aim of this study was to investigate the impact of two nest-building materials, hessian and straw, on peri-parturient sow behaviour, plasma cortisol concentration and piglet survival and performance in farrowing crates. In the first experiment, sows (parity 1.7 ± 0.1) were allocated to four treatments: (n = 15), straw provided in the lead up to farrowing in an open farrowing pen, with the pen closed after farrowing (STRAW OPEN); (n = 14), straw provided in the lead up to farrowing in a closed farrowing pen (STRAW CLOSED); (n = 15), a closed farrowing pen with hessian sacks provided in the lead up to farrowing (HESSIAN) and; (n = 13), a closed farrowing pen with no nesting materials provided (CONTROL). A second experiment was performed on a separate farm to assess the effect of the same four treatments were applied to sows (parity 2.9 ± 0.1): SRAW OPEN (n = 68), STRAW CLOSED (n = 64), HESSIAN (n = 66) and CONTROL (n = 66), at a commercial level. The first experiment revealed that providing conventionally housed sows with straw or hessian in the lead up to parturition stimulated sows to perform nest-building behaviours similar to sows housed in an open pen with access to straw (nosing events; 16 ± 11 (CONTROL); 169 ± 36 (HESSIAN); 118 ± 29 (STRAW CLOSED); 199 ± 53 (STRAW OPEN); P < 0.05). Additionally, crated sows provided with straw had reduced cortisol levels immediately after farrowing compared to all other treatments (21.9 ± 6.1 ng/ml vs CONTROL; 49.3 ± 8.6 ng/ml; P < 0.01). Piglets born to STRAW CLOSED sows displayed the highest colostrum intake levels (404.8 ± 22.7 g vs CONTROL 361.9 ± 21.9 g; P < 0.01). The second experiment demonstrated a reduced incidence of piglet mortality both prior to fostering (0.7 ± 0.2; P = 0.001) and after fostering (0.7 ± 0.2; P = 0.001) in litters born to sows which were housed in conventional farrowing crates and provided with straw compared to CONTROL (prior to fostering 1.3 ± 0.2, and postfostering 1.1 ± 0.2). In conclusion, straw and hessian sacks are a suitable substrate for stimulating sows to exhibit nest-building behaviour under crated conditions. However, only the provision of straw in the crate environment improved piglet survival and positively affected sow welfare.


Treatment of Parkinson's disease with sodium valproate: clinical, pharmacological, and biochemical observations.
Because there is biochemical evidence of decreased GABAergic function in Parkinson's disease, sodium valproate, an inhibitor of GABA catabolism, was administered to eight Parkinsonian patients. Valproate treatment did not significantly alter any Parkinsonian feature, but tended to increase the dyskinesia in the "on-off" patients. The increased dyskinesias were not a result of altered peripheral metabolism of L-dopa. Despite obtaining high plasma levels of valproate, no consistent alteration of CSF GABA levels could be demonstrated. Thus, in these patients, an effect of valproate on GABA metabolism is unproven, and in turn, the role of GABA in Parkinsonism and dyskinesia uncertain.


Mono-(2-ethylhexyl) phthalate affects the steroidogenesis in rat Leydig cells through provoking ROS perturbation.
Di-2-ethylhexyl phthalate (DEHP), one of the most widely used plasticizers in a number of day-life products, exerts both short-term and long-lasting effects on testicular steroidogenesis during in utero exposure. These actions might be caused by its primary metabolite, mono-(2-ethylhexyl) phthalate (MEHP). In the present study, we investigated the effects of MEHP on steroidogenesis of different stages of rat Leydig cells, progenitor (PLCs), immature (ILCs) and adult (ALCs). Results showed that MEHP affected reactive oxygen species (ROS) generation as well as androgen production in ALCs, but not in PLCs and ILCs, which coincided with hydrogen peroxide (H(2)O(2)). Low concentrations of MEHP (20-200μM) provoked ROS perturbation and caused the stimulation of steroidogenic acute regulatory (StAR), cytochrome P450 side-chain cleavage (P450scc), 3β-hydroxysteroid dehydrogenases (3β-HSD) and 17β-hydroxysteroid dehydrogenases (17β-HSD) activities which elevated T production of ALCs. Contrast to the effect in low doses, high levels of MEHP (2000μM and over) induced overloaded oxidative stress and inhibited steroidogenesis by reducing the activities of these enzymes in ALCs. These results indicated that oxidative stress and subsequent steroidogenic enzymes changes in ALCs were the potential underlying mechanism of the biphasic effects of DEHP on androgen production.


Clinical characteristics, cytokine profiles and plasma IgE in adults with asthma.
Asthma is a disease with complicated network of inflammatory responses of cytokines and ImmunoglobulinE (IgE). The aim of this study was to explore the clinical characteristics, cytokine profile and plasma IgE in the Malaysian population. This is a cross-sectional study involving physician-diagnosed asthma patients (n = 287) recruited from the Chest Clinic, University of Malaya Medical Centre (UMMC). Blood (8 mL) was taken after consent was obtained. The peripheral blood leucocytes (PBL) were cultured in presence of a mitogen for 72 h to quantify cytokines [Interleukin-5(IL-5), Interleukin-9 (IL-9), Interleukin-12 Beta (IL-12ꞵ) and granulocyte-macrophage colony-stimulating factor (GM-CSF)] and plasma was used to quantify IgE levels with commercial ELISA kits. Results were compared against the same biomarkers in healthy subjects (n = 203). In addition, the amount of the biomarkers in the asthma patients were compared with their disease severity and clinical characteristics. Statistical tests in the SPSS software (Mann-Whitney U test and the Kruskal Wallis) were used to compare cytokine production and plasma IgE levels. The mean plasma IgE level was markedly higher (p < 0.0001) in asthmatics compared to controls. There were higher levels of IL-5, IL-9, IL-12ꞵ and GM-CSF (p < 0.0001) produced by cultured PBL from asthma patients compared to controls. However, our results did not expose a significant association between these cytokine levels and severity and clinical symptoms of asthma. However, there was a marked association between asthma severity and blood lymphocyte count [ꭓ2(2) = 6.745, p < 0.05]. These findings support the roles played by cytokines and IgE in the airway inflammation in asthma. The findings of this study provide new information about inflammatory cytokines in Malaysian asthma patients.


Dominant role of mitochondria in clearance of large Ca2+ loads from rat adrenal chromaffin cells.
Cytosolic Ca2+ (Ca2+c) clearance from adrenal chromaffin cells was studied by whole-cell patch clamp and indo-1 Ca2+ photometry after influx of Ca2+ through voltage-dependent Ca2+ channels. We isolated the rates of Ca2+c clearance by several mechanisms using combinations of the following agents (with their expected targets): Li+ or TEA substituted for Na+ (Na(+)-Ca2+ exchange), 1 mM La3+ applied after the depolarization (Na(+)-Ca2+ exchange and plasma membrane Ca(2+)-ATPase), 1 microM thapsigargin (pumping into reticular stores), and 2 microM carbonyl cyanide m-chlorophenylhydrazone (uptake into mitochondria). Remarkably, whenever [Ca2+]c rose above approximately 500 nM, Ca2+c clearance by mitochondria exceeded clearance by either Na(+)-Ca2+ exchange or the Ca2+ pumps of the plasma and reticular membranes. As [Ca2+]c fell again, Ca2+ reemerged from mitochondria, prolonging the final return to basal levels.


Genetic relationship, population structure analysis and pheno-molecular characterization of rice (Oryza sativa L.) cultivars for bacterial leaf blight resistance and submergence tolerance using trait specific STS markers.
Rice is an important source of calorie for the growing world population. Its productivity, however is affected by climatic adversities, pest attacks, diseases of bacterial, viral and fungal origin and many other threats. Developing cultivars that are high yielding and stress resilient seems a better solution to tackle global food security issues. This study investigates the potential resistance of 24 rice cultivars against Xanthomonas oryzae pv. Oryzae (Xoo) infection that causes bacterial leaf blight disease and submergence stress. Bacterial leaf blight (BLB) resistance genes (Xa4, xa5, xa13, Xa21, Xa38) and submergence tolerance (Sub1) gene specific markers were used to determine the allelic status of genotypes. The results displayed presence of Xa4 resistance allele (78.95%), xa5 (15.79%) but xa13 and Sub1 tolerance allele were not found in any genotype. However, a new allele for Xa21 (84.21%) and Xa38 (10.52%) were identified in several genotypes. Phenotypic screening for both stress conditions was done to record the cultivars response. None of the genotypes showed resistance against Xoo, although varieties viz., Tapaswini and Konark showed moderate susceptibility. Likewise, survival percentage of genotypes under submergence stress varied from 0 to 100%. Tolerant checks FR13A (100%) and Swarna Sub1 (97.78%) exhibited high survival rate, whereas among genotypes, Gayatri (57.78%) recorded high survivability even though it lacked Sub1 tolerant its genetic background. A total of six trait specific STS and two SSR markers generated an average of 2.38 allele per locus. Polymorphism information content (PIC) value ranged from 0.08 to 0.42 with an average of 0.20. Structure analysis categorized 24 genotypes into two sub-populations, which was in correspondence with Nei's genetic distance-based NJ tree and principal co-ordinate analysis (PCoA). Swarna Sub1 could be differentiated clearly from BLB resistant check, IRBB60 and other 22 genotypes without having Sub1 gene. Analysis of molecular variance (AMOVA) revealed more genetic variation within population than among population. Principal component analysis (PCA) showed that 9 morphological traits collectively explained 76.126% of total variation among all the genotypes studied. The information from this study would be useful in future breeding programs for pyramiding trait specific genes into high yielding cultivars that fall behind with respect to stress resilience. The online version contains supplementary material available at 10.1007/s12298-021-00951-1.


Current Understanding of the Pathophysiology and Approach to Tension-Type Headache.
Description of headache dates back thousands of years, and to date, tension-type headache (TTH) remains the most common form of headache. We will review the history and current understanding of the pathophysiology of TTH and discuss the recommended clinical evaluation and management for this syndrome. Despite being the most prevalent headache disorder, TTH pathophysiology remains poorly understood. Patients with TTH tend to have muscles that are harder, more tender to palpation, and may have more frequent trigger points of tenderness than patients without headache. However, cause and effect of these muscular findings are unclear. Studies support both peripheral and central mechanisms contributing to the pain of TTH. Diagnosis is based on clinical presentation, while the focus of evaluation is to rule out possible secondary causes of headache. Treatment options have remained similar over the course of the past decade, with some additional studies supportive of both pharmacological and non-pharmacological options. An approach to TTH has been outlined including historical context, evolution over time, and the best evidence regarding our current understanding of the complex pathophysiology and treatment of this disease.


Three Methods for Peptide Cyclization Via Lactamization.
Lactamization is the key step in the synthesis of many compounds with macrocyclic structure. As the interest for these types of molecules grows in various fields such as drug discovery and nanomaterials, different methodologies to access them are being developed. Three different strategies to obtain cyclic peptides via lactamization are described in this chapter: solution-phase macrocyclization following solid-phase peptide synthesis (SPPS) of the linear precursor, SPPS and on-resin cyclization on the 2-chlorotrityl chloride (2-CTC) resin, and SPPS and on-resin cyclization by native chemical ligation on the amino-PEGA resin.


Half-filter experiments for assignment, structure determination and hydration analysis of unlabelled ligands bound to 13C/15N labelled proteins.
A novel variant of the 13C/15N ω2 half-filter experiment is reported for studying the hydration of an unlabelled ligand bound to a 15N and 13C uniformly labelled biological macromolecule. This doubly tuned filter experiment represents a powerful tool for obtaining resonance assignments, structure determination and hydration properties of a ligand. Its application to the binary complex formed by the inserted-domain (I-domain) of the leukocyte function-associated antigen-1 (LFA-1) with a ligand reveals the presence of H2O molecules at the binding interface.


Regulation of Th2 responses by different cell types expressing the interleukin-31 receptor.
Interleukin-31 (IL-31) is a recently identified cytokine produced by Th2 cells that is involved in the development of atopic dermatitis-induced skin inflammation and pruritus. Its receptor, IL-31RA, is expressed by a number of cell types, including epithelial cells, eosinophils, and activated monocytes and macrophages. To date, however, the regulation of Th2 responses by distinct cell types and tissues expressing IL-31RA has not been well studied. In this study, Cry j 2, one of the major allergens of Japanese cedar pollen, was administered to IL-31RA-deficient or wild-type (WT) mice via nasal or intraperitoneal injection for induction of specific Th2 responses. After nasal administration of Cry j 2, IL-31RA-deficient mice showed lower Cry j 2-specific CD4+ T cell proliferation, Th2 cytokine (IL-5 and IL-13) production, and Th2-mediated (IgE, IgG1, and IgG2b) antibody responses than WT mice. In contrast, IL-31RA-deficient mice administered Cry j 2 intraperitoneally showed stronger Th2 immune responses than WT mice. These results indicate that IL-31R signaling positively regulates Th2 responses induced by nasal administration of Cry j 2, but negatively regulates these responses when Cry j 2 is administered intraperitoneally. Collectively, these data indicate that the induction of antigen-specific Th2 immune responses might depend on tissue-specific cell types expressing IL-31RA.


Methyleugenol as a surgical anesthetic in rodents.
The in vivo administration of 59Fe to the rat accompanied by acetylsalicylic acid (ASA) enhanced significantly counts in blood, spleen, liver and femur without affecting those of the intestine. The results suggest that ASA augments iron absorption either via an inhibitory action on the synthesis of prostaglandins or by a purely chemical mechanism.


Modulatory effect of neurosteroids in haloperidol-induced vacuous chewing movements and related behaviors.
Tardive dyskinesia is a syndrome of abnormal and involuntary movements which occurs as a complication of long-term neuroleptic therapy especially classical neuroleptics such as haloperidol and chlorpromazine. Dysfunction of GABA receptor mediated inhibition, and increased glutamatergic neurotransmission has been implicated in the development of orofacial dyskinesia in rats and tardive dyskinesia in humans. Neurosteroids modulate both GABAergic as well as glutamatergic neurotransmission in various brain areas. The objective of the present study was to elucidate the role of various neurosteroids in neuroleptic-induced vacuous chewing movements and related behaviors in rats by using behavioral, biochemical, and neurochemical parameters. Animals chronically treated with haloperidol (1 mg/kg i.p.) for a period of 21 days exhibited marked increase in vacuous chewing movements, tongue protrusions, and facial jerkings as compared to vehicle-treated controls. It also resulted in increased superoxide anion levels and lipid peroxidation, whereas decreased levels of endogenous antioxidant enzymes (catalase and superoxide dismutase) in rat brain striatum homogenates. Neurochemical studies revealed that chronic administration of haloperidol resulted in significant decrease in the levels of dopamine, serotonin, and norepinephrine in rat brain striatum homogenates, whereas urine biogenic amines metabolite levels were increased. In a series of experiments, rats co-administered with allopregnanolone (0.5, 1, and 2 mg/kg i.p.) and progesterone (5, 10, and 20 mg/kg i.p.), both positive GABA-modulating [negative N-methyl-D-aspartate (NMDA)-modulating] neurosteroids prevented, whereas pregnenolone (0.5, 1, and 2 mg/kg i.p.) and dihydroxyepiandrosterone sulfate (0.5, 1, and 2 mg/kg i.p.) both negative GABA-modulating (positive NMDA-modulating) neurosteroids aggravated all the behavioral, biochemical, and neurochemical parameters. These results suggest that neurosteroids may play a significant role in the pathophysiology of vacuous chewing movements and related behaviors by virtue of their action on either the GABA or NMDA modulation. Furthermore, neurosteroids showing selectivity for positive GABA modulation and/or negative NMDA modulation may be particularly efficacious as novel therapeutic agents for the treatment of tardive dyskinesia and deserve further evaluation.


Insulin and glucagon secretion in diabetic and non-diabetic patients with circulating islet cell antibodies.
Thirty-nine patients (14 non-diabetics, 8 chemical diabetics, and 17 overt diabetics) with circulating islet cell antibodies (ICA) were studied. Insulin and glucagon secretion after oral (100 g) and intravenous glucose loading (200 mg/kg bolus injection followed by an infusion of 20 mg/min over 60 min) and arginine infusion (25 g over 30 minutes) were evaluated in these patients and in non diabetic and diabetic ICA-negative controls. In the non-diabetic groups with or without ICA, insulin and glucagon responses to glucose were similar. Moreover, in ICA positive patients the response of these hormones to arginine infusion was reduced. Similar alterations in insulin and glucagon secretion were observed in the CIA positive and negative patients with chemical or overt diabetes. In particular, fasting hyperglucagonaemia and glucagon hyperresponse to arginine are associated with a lack of insulin secretion in the patients with overt diabetes. Hormonal differences between diabetics with and without ICA could not be detected.


Short uncemented femoral component for hip revision: prognosis and risk factors associated with failure.
The application of short femoral stems is partially restricted in revision surgery. This study will demonstrate the therapeutic effect and unsuitable situation for short stem revision. Demographic characteristics of all patients were recorded in detail (Table 1). Anteroposterior view radiographic examinations of proximal femur are necessary before and after the operation for patients. The primary outcome of interest was the survival rate of the femoral stem at the final follow-up. Risk factors for failure were also investigated. The secondary outcomes of interest included the Harris hip score, excellent to good rate and incidence of complications. The Mann-Whitney U test was performed for comparisons between continuous variables. The chi-square test was performed for comparisons between categorical variables. Cox regression analysis was used to assess the association between potential risk factors and the failure of revision surgery. A total of 381 patients with short stems were retrospectively reviewed. There were 188 males and 193 females. The average age and body mass index before revision surgery were 58.85 ± 13.46 years and 23.72 ± 3.40 kg/m2, respectively. The mid-term survival rate of the short femoral component was 94.23%. The prognosis and complications of patients between the two groups were compared. There was no significant difference between the two groups in the Harris score, complication incidence or survival rate of the femoral component. The strongest risk factor in this study was intraoperative periprosthetic femoral fracture during revision surgery (HR = 5.477, 95% CI = 2.156-13.913). Three risk factors for failure were identified: ageing, osteoporosis and intraoperative periprosthetic femoral fracture during revision surgery. Therefore, a short femoral stem should be implanted in patients with these risk factors with additional caution.


Histological heterogeneity of glomerular segmental lesions in focal segmental glomerulosclerosis.
Focal segmental glomerulosclerosis (FSGS) involves considerable histological heterogeneity in terms of location and quality of the glomerular segmental lesions. The present study investigated the heterogeneity of segmental lesions in each variant of FSGS, determined by the Columbia classification, and its clinical relevance. All glomerular segmental lesions of 80 cases of primary FSGS were evaluated histologically based on location [tip (TIP), perihilar (PH), or not otherwise specified (NOS)], and quality (cellular or fibrous). Among the 1,299 glomeruli of the 80 biopsy specimens, 210 glomeruli (16.2%) had segmental lesions, comprising 57 (27%) cellular TIP, 4 (2%) fibrous TIP, 42 (20%) cellular NOS, 86 (41%) fibrous NOS, and 21 (10%) fibrous PH lesions. Each case was also classified into one of the five histological variants of the Columbia classification: collapsing (COL), TIP, cellular (CEL), PH, or NOS. Overlap of segmental lesions in different location categories was seen in the COL, TIP, and PH variants, and heterogeneity of quality was apparent in the COL and CEL variants. Histological findings of the CEL variant (endocapillary hypercellularity) were observed in nine of the 13 COL variants. Both location and quality correlated with disease duration, degree of proteinuria, and histological severity of global glomerular sclerosis and tubulo-interstitial lesions. These results demonstrated the histological heterogeneity of glomerular segmental lesions in all variants of the Columbia classification, except NOS. However, the fidelity of location and dominance of histological features were generally conserved in the TIP and PH variants. The COL and CEL variants warrant further investigation because of their overlapping histological findings and apparent histological heterogeneity in the glomerular segmental lesions.


Sulfhydryl groups are involved in H+ translocation via the uncoupling protein of brown adipose tissue mitochondria.
Mersalyl inhibits H+ transport via the uncoupling protein (UP) in brown adipose tissue (BAT) mitochondria estimated as swelling in potassium acetate (Ki 67 microM) or as valinomycin-induced H+ extrusion in K2SO4 (Ki 55 microM) and KCl. The swelling in KCl is depressed only slightly. Some other SH-reagents (p-hydroxymercuribenzoate, 5,5'-dithiobis(2-nitrobenzoate) and thiolyte DB), but not hydrophobic reagents (N-ethylmaleimide and eosin-5-maleimide), exhibit analogous inhibition. Thus an essential SH-group localized at the water-accessible cytosolic surface of UP was found to be involved in H+ transport via UP but not in Cl- transport.


Neonatal outcome of IVF singletons versus naturally conceived in women aged 35 years and over.
To compare the delivery and neonatal outcome of IVF singleton pregnancies with those conceived spontaneously in primiparous women ≥ 35 years of age. Data were collected by the hospital's obstetrics and pediatric staff at the time of examination, hospitalization, delivery and discharge. A total of 283 women with in vitro fertilization (IVF) singleton deliveries were matched according to ethnicity, age, gravidity, smoking habits, body mass index, weight gain in pregnancy, site and time of delivery with consecutive 283 women conceived spontaneously. The outcome measures were mode of delivery, birth weight, preterm birth and perinatal mortality. Cesarean delivery rate was more common in IVF pregnancies (39.9% vs. 25.1%; p < 0.001). Preterm delivery rate, specifically of spontaneous onset was significantly higher in IVF group (18.7%) than in spontaneous conception group (10.3%; p < 0.008). No difference was found in birth weight records (SGA, VLBW, LBW and LGA) or perinatal mortality rate. However, average gestational birth weight was lower among infants conceived after IVF (3,050 ± 587 g vs. 3,130 ± 524 g; p < 0.05). Singleton IVF pregnancies in primiparous women ≥ 35 years of age have increased perinatal risk associated with higher rates of cesarean section, preterm births and infants of lower average birth weight. Nevertheless, pregnancy and delivery complications, number of infants with low or very low birth weight, small or large birth weight for appropriate gestation did not differ from those of the spontaneous conceptions.


[Anaesthesia in noma-patients - facts and management of a forgotten disease].
Noma (cancrum oris) is an unspecific bacterial infection in the oro-facial area. In the industrial countries noma is generally unknown, but in the 3rd world - especially in West Africa - it is widespread and one of the main causes of mortalitiy and reason for disability in children. Pathogenesis, clinical course, management and treatment of noma are described with the consequences for anaesthesia.


Equations for estimating the oxygen cost of walking in stroke patients: Systematic review.
To report all equations that can potentially be used to estimate the oxygen cost of walking (Cw) without using a respiratory gas exchange analyzer and to provide the level of reliability of each equation. Webline, Medline, Scopus, ScienceDirect, Bielefeld Academic Search Engine (BASE), and Wiley Online Library databases from 1950 to August 2019 with search terms related to stroke and oxygen cost of walking. This systematic review was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the methodological quality of included studies was determined with the Critical Appraisal Skills Programme (CASP). We screened 2065 articles, and 33 were included for full-text analysis. Four articles were included in the data synthesis (stroke individuals=184). Analysis reported 4 equations estimating Cw that were developed from logistic regression equations between Cw and self-selected walking speed. The equations differed in several methodological aspects (characteristics of individuals, type of equation, Cw reference measurement methods). The Compagnat et al. study had the highest quality (CASP score=9/9). This literature review highlighted 4 equations for estimating Cw from self-selected walking speed. Compagnat et al. presented the best quality parameters, but this work involved a population restricted to individuals with hemispheric stroke sequelae.


A comparison of how families and their service providers rate family generated quality of service factors.
This paper presents a method which was utilized to obtain family consensus around the criteria which should be used to evaluate family support programs. Twelve family members of persons with developmental disabilities were selected in each of six different sites to participate in a group process to identify the factors which distinguish quality family support programs. Content analysis of the results of the six meetings resulted in a final list of 15 quality factors. Two hundred and sixty one families and their family support coordinators (N = 65) were asked to rate the importance of each factor on a 10 point scale. Analysis revealed that there was high agreement between families and their coordinators on the importance of all 15 factors. The applicability of the method used to obtain family consensus regarding evaluation criteria for community mental health agencies is discussed.


Expression of the movement protein of Tomato spotted wilt virus in its insect vector Frankliniella occidentalis.
Tomato spotted wilt virus (TSWV) is able to infect both its botanical hosts and its insect vector (thrips). In plant tissue the NS(M) protein of TSWV functions as viral movement protein (MP), aggregating into plasmodesma-penetrating tubules to establish cell-to-cell movement. As upon heterologous expression NS(M) was able to form similar tubules on the surface of insect (Spodoptera frugiperda) cells, we have now investigated the expression and cellular manifestation of this protein in infected thrips tissue. It is shown that NS(M), though detectably expressed in both the L2 larval and adult thrips stages, does not aggregate into tubules, indicating that this requirement is associated to its function as MP in plants, and raising the question if NS(M) has a function at all during the insect life cycle of TSWV.


Decoding the Complex Crossroad of Tryptophan Metabolic Pathways.
Among the 20 amino acids needed for protein synthesis, Tryptophan (Trp) is an aromatic amino acid fundamental not only for the synthesis of the major components of living cells (namely, the proteins), but also for the maintenance of cellular homeostasis [...].


Automated label-free detection of injured neuron with deep learning by two-photon microscopy.
Stroke is a significant cause of morbidity and long-term disability globally. Detection of injured neuron is a prerequisite for defining the degree of focal ischemic brain injury, which can be used to guide further therapy. Here, we demonstrate the capability of two-photon microscopy (TPM) to label-freely identify injured neurons on unstained thin section and fresh tissue of rat cerebral ischemia-reperfusion model, revealing definite diagnostic features compared with conventional staining images. Moreover, a deep learning model based on convolutional neural network is developed to automatically detect the location of injured neurons on TPM images. We then apply deep learning-assisted TPM to evaluate the ischemic regions based on tissue edema, two-photon excited fluorescence signal intensity, as well as neuronal injury, presenting a novel manner for identifying the infarct core, peri-infarct area, and remote area. These results propose an automated and label-free method that could provide supplementary information to augment the diagnostic accuracy, as well as hold the potential to be used as an intravital diagnostic tool for evaluating the effectiveness of drug interventions and predicting potential therapeutics.


Metabolite profiles of Gansuibanxia decoction in rat plasma and urine by UHPLC-Q-TOF/MS analysis.
Gansuibanxia decoction (GSBXD), a traditional Chinese medicine (TCM) formula with 2000 years of history, has good efficacies on treating cancerous ascites, pleural effusion, etc. However, little is known about its metabolite profiles owing to the lack of in vivo studies. In this study, we explored the prototypes and metabolites of GSBXD in rat plasma and urine using UHPLC-Q-TOF/MS technology. A total of 82 GSBXD-related xenobiotic bioactive components (38 prototypes and 44 metabolites) were confirmed or tentatively characterized, including 32 prototypes and 29 metabolites in plasma, and 25 prototypes and 29 metabolites in urine. The results showed that the bioactive components absorbed in vivo mainly contained diterpenoids, triterpenoids, flavonoids and monoterpene glycosides. Both phase I reactions (methylation, reduction, demethylation, hydrolysis, hydroxylation and oxidation) and phase II reactions (glucuronidation and sulfation) were involved in the metabolism of GSBXD in vivo. This study will provide a foundation for the quality control, pharmacological study and clinical application of GSBXD.


[Phosphodiesterase 4 inhibition for treatment of endothelial barrier and microcirculation disorders in sepsis].
Sepsis is commonly associated with loss of microvascular endothelial barrier function (capillary leak) and dysfunctional microcirculation, which both promote organ failure. The development of a distinct therapy of impaired endothelial barrier function and disturbed microcirculation is highly relevant because both of these phenomena constitute crucial processes which critically influence the prognosis of patients. Numerous in vivo and in vitro trials over the past years have fostered a better understanding of the pathophysiology of capillary leak. Furthermore, promising data in animal models show that therapeutic modulation of endothelial barrier function and microcirculation can be achieved by stabilizing endothelial cAMP (cyclic adenosine monophosphate) levels followed by activation of Rho-GTPase Rac1, e. g. by phosphodiesterase 4 inhibitors. This review summarizes and discusses recent findings of cellular mechanisms and in vivo trials.


A supramolecular nanocarrier for efficient cancer imaging and therapy by targeting at matriptase.
Human serum albumin (HSA), a versatile protein carrier for endogenous and exogenous compounds, is a proven macromolecule to form nanoparticles for drug delivery. To render HSA carrier specificity toward tumors, we designed a recombinant HSA protein fused with Kunitz domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 1, which targets to matriptase, a type II transmembrane serine protease overexpressed on tumor cell surface. The carrier was thus named matriptase targeting carrier (MTC). In this study, we showed that MTC displayed the same inhibitory potency as the KD1 againast matriptase, demonstrating the HSA fusion did not affect the KD1 targeting potency. For tumor optical imaging and ablation, MTC was prepared as nanoparticle drug carrier by a novel method via denaturation and refolding to incorporate photosensitizer, CPZ. This matriptase targeting nanoparticles, CPZ:MTC@NPs, showed high specificity and cytotoxicity for matriptase-overexpressing cancer cells in vitro. In tumor-bearing mice, CPZ:MTC@NPs demonstrated selective accumulation and high retention in matriptase-overexpressing tumor. Under illumination, the nanoparticles significantly reduced tumor volumes (79.6%) as compared to saline control. These findings showed that this supramolecular nanocarrier, a new type of tumor targeting self-assembly nanoparticle, had potential as a highly efficient tumor targeting drug carrier for imaging and therapy.


Therapeutic effects of medicinal plants on isoproterenol-induced heart failure in rats.
Natural products still serves as a hope for some illnesses which modern medicine fails to cure. Many people, either knowing their effects or not, are using these herbal products. Treatment of chronic heart failure (CHF) is yet a complicated clinical challenge and there is need to improve or make new therapeutic targets. Finding new agents for CHF is an important subject in cardiovascular drug research. In this study, we evaluated the effects of ten herbals on treatment of CHF on isoproterenol-induced model. Ninety-six male Wistar rats (16 weeks old) were used in 12 groups. Transthoracic echocardiography was performed on the rats for confirmation of CHF model by decreasing ejection fraction. After 4 weeks' treatment, hearts were removed and blood samples were collected in tubes to measure plasma levels of laboratory findings. Our results showed that the mean of ejection fraction in model rats was 51.82 ± 3.49 percent and all of our used natural products could significantly increase the ejection fraction (P < 0.01). The most effective herbals in improving the ejection fraction were Allium sativum (30.69 %), Peganum harmala (26.08 %) and Apium graveolens (24.09 %). The best results in decreasing NT-ProBNP, was obtained from Allium sativum, Peganum harmala and Berberis vulgaris respectively. Our results showed that none of natural products had toxic effect on renal and liver tissues. Our results showed that Allium sativum, Peganum harmala and Berberis vulgaris could significantly improve cardiac function by improvement of left ventricular remodeling, lowering hs-CRP and NT-ProBNP and echocardiographic indexes without liver or renal side effects.


Relationship Between Gastric Emptying Rate and Simultaneously Assessed Symptoms in Functional Dyspepsia.
During a GE test (breath test with 13C-octanoic acid labelled 250 kcal solid meal), the severity of 6 symptoms (postprandial fullness, epigastric pain and burning, bloating, nausea and belching) was assessed, every 15 min, before meal-intake and 4h postprandially. The sum of individual symptom scores generated the meal-related symptoms score; the sum of all symptoms generated overall meal-related symptom severity (OSS). Data were compared in patients with normal and delayed GE (cut-off T1/2≥ 109 min). Data are shown as mean±SEM. 504 patients were included, of which 382 patients (67% female, age 43.8±0.8 years, BMI 23.3±0.2 kg/m2) had normal and 122 patients (77% female, age 42.7±1.5 years, BMI 23.2±0.6 kg/m2) had delayed GE. OSS tended to be higher in patients with delayed GE (81.8±3.4 vs. 99.5±7.1, p=.05). Only nausea was significantly higher in patients with delayed GE (11±0.8 vs. 16±1.6, p=.01). No correlations were observed between GE rate and any of the symptoms (OSS: r=0.06, p=.2; nausea: r=0.06, p=.1). The symptom severity time course showed a significant difference only for nausea, with increased severity ratings 90 min after the meal (p<.01) in delayed GE compared to normal GE patients. The severity of symptoms in functional dyspepsia and idiopathic gastroparesis, even when assessed during the GE test meal, is not correlated to gastric emptying rate. (Ethics committee University Hospital of Leuven study number S55426).


Effect of human tumor antigens on the active E-rosette-forming test (ARFT): a new diagnostic method for cancer.
The "active" T-cell test was adapted into an in vitro assay for response to human tumor antigens, especially gastric, lung, liver, esophageal, and colonic tumors. Peripheral blood lymphocytes were isolated from 229 cancer patients, 60 non-cancer patients, and 70 normal adults. Tumor antigen, incubated with lymphocytes from patients with the corresponding cancer, produced a significant increase in the ability of the lymphocytes to function as active rosette-forming cells (ARFC) when compared with lymphocytes cultured without antigen (P less than 0.001). This potentiating effect on ARFC remained unimpaired even after tumor antigen refrigeration. Tumor antigen incubated with lymphocytes from normal donors produced no increase in ARFC ability. This assay appears to be specific for the antigen corresponding to the cancer of the given patient; for example, gastric tumor antigen increased the ARFC of gastric cancer patients, but produced no increase in ARFC of breast cancer patients. No interference by the HLA complex was found in this assay. This technique provides a novel in vitro method for investigating cell-mediated immunity and also a new, specific method for cancer diagnosis.


In vivo relaxation of N-acetyl-aspartate, creatine plus phosphocreatine, and choline containing compounds during the course of brain infarction: a proton MRS study.
Localized water suppressed proton spectroscopy has opened up a new field of pathophysiological studies of severe brain ischemia. The signals obtained with the pulse sequences used so far are both T1 and T2 weighted. In order to evaluate the extent to which changes in metabolite signals during the course of infarction can be explained by changes in T1 and T2 relaxation times, eight patients with acute stroke were studied. STEAM sequences with varying echo delay times and repetition times were used to measure T1 and T2 of N-acetyl-aspartate (NAA), creatine plus phosphocreatine (Cr+PCr) and choline containing compounds (CHO) in a 27-ml voxel located in the affected area of the brain. Ten healthy volunteers served as controls. We found no difference in T1 or T2 of the metabolites between the patients and the normal controls. The T2 of CHO was longer than that of NAA and Cr+PCr. Our results indicate that spectra obtained in brain infarcts and normal tissue with the same acquisition parameters are directly comparable with respect to relative signal intensities as well as signals scaled with internal and external standards.


The association between XPD Asp312Asn polymorphism and lung cancer risk: a meta-analysis including 16,949 subjects.
To derive a more precise estimation of the relationship between the xeroderma pigmentosum group D (XPD) Asp312Asn polymorphism and lung cancer risk, a meta-analysis was performed. PubMed, Medline, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the XPD Asp312Asn polymorphism and lung cancer risk. The pooled ORs were performed with co-dominant model (Asp/Asn vs. Asp/Asp, Asn/Asn vs. Asp/Asp), dominant model (Asp/Asn + Asn/Asn vs. Asp/Asp), and recessive model (Asn/Asn vs. Asp/Asp+Asp/Asn), respectively. A total of 18 studies including 7,552 cases and 9,397 controls were involved in this meta-analysis. Overall, significantly elevated lung cancer risk was associated with XPD Asn allele when all studies were pooled into the meta-analysis (Asn/Asn vs. Asp/Asp: OR=1.158, 95% CI=1.018-1.317; recessive model: OR=1.161, 95% CI=1.029-1.311). In the subgroup analysis by ethnicity, significantly increased risks were found for both Caucasians (Asn/Asn vs. Asp/Asp: OR=1.164, 95% CI=1.003-1.351; recessive model: OR=1.169, 95% CI=1.016-1.345) and Asians (Asn/Asn vs. Asp/Asp: OR=8.056, 95% CI=2.420-26.817; recessive model: OR=7.956, 95% CI=2.391-26.477). When stratified by study design, statistically significantly elevated risk was noted in hospital-based studies (Asn/Asn vs. Asp/Asp: OR=1.315, 95% CI=1.110-1.558; recessive model: OR=1.290, 95% CI=1.099-1.513). In conclusion, this meta-analysis suggests that the XPD Asn allele is a low-penetrant risk factor for developing lung cancer.


Rapamycin protects against apoptotic neuronal death and improves neurologic function after traumatic brain injury in mice via modulation of the mTOR-p53-Bax axis.
Rapamycin has proven to be a neuroprotective agent in traumatic brain injury (TBI). However, there is a lack of data regarding the effect of rapamycin on apoptotic neuronal death after TBI. Thus, the present study was designed to detect the modulatory role of rapamycin on apoptosis and explore the potential involvement of the mammalian target of rapamycin (mTOR)-p53-Bax axis after TBI. Neurologic severity score tests were performed to measure behavioral outcomes. The effect of rapamycin treatment on neuronal death was analyzed using immunofluorescence analysis of NeuN. Terminal deoxynucleotidyl transferase-mediated dUTP nick 3'-end labeling was performed to detect apoptotic cells. The expression of Bax and phosphorylated protein of p53 was detected using Western blotting analyses and immunofluorescence staining. Phosphorylated protein of the mTOR in the ipsilateral cortex was detected using Western blotting analyses. Rapamycin administration after TBI was associated with an increased number of neurons, decreased apoptosis index, and improved neurobehavioral function, which was potentially mediated by inactivation of the mTOR-p53-Bax axis. Rapamycin can protect neurons from apoptotic neuronal death after TBI. This study presents a new insight into the antiapoptosis mechanisms, which are responsible for the neuroprotection of rapamycin, with the potential involvement of the mTOR-p53-Bax axis.


Differences in sex- and age-associated mortality in patients with anti-MDA5-positive dermatomyositis.
The effect of sex and age on the outcomes of patients with anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (MDA5+ DM) remains unclear. This study aimed to investigate the impact of sex and age on the prognosis of patients with MDA5+ DM. We included 251 patients (women, 156; men, 95), who were newly diagnosed with MDA5+ DM between 2014 and 2021. The outcome was 6-month all-cause mortality after the diagnosis of interstitial lung disease. Cox regression analysis was used to assess the mortality. Adjusted restricted cubic spline analysis was performed to explore the non-linear relationship between age and outcomes. The 6-month mortality rates of women and men were 36.5% and 46.3%, respectively. Multivariate Cox regression revealed that ≥60 years of age was significantly associated with the risk of death (hazard ratio, 2.43; 95% confidence interval, 1.02-5.78). The trend of the risk of 6-month mortality in men was relatively flat until 54 years and increased rapidly afterwards (hazard ratio, 1.14; 95% confidence interval, 1.01-1.29). In contrast, the 6-month mortality rate showed a low linear increasing trend with age among females. Patients with MDA5+ DM, who received contemporary treatment, had unfavourable outcomes. The 6-month mortality risk increased with age, particularly in male patients aged >54 years.


Identification of single nucleotide polymorphisms in the human kallikrein 10 (KLK10) gene and their association with prostate, breast, testicular, and ovarian cancers.
The KLK10 gene (also known as the normal epithelial cell-specific 1 gene) is a member of the expanded human kallikrein gene family. Recently, it has been reported that KLK10 is a tumor suppressor gene and that its expression is downregulated in various forms of cancer and cancer cell lines. KLK10 is also upregulated in ovarian cancer. We thus hypothesized that the KLK10 gene may be a target for mutations in various cancers. We sequenced the five coding exons of the KLK10 gene using genomic DNA from various tumors, normal tissues, and blood, by PCR amplification and automated sequencing. In none of the tumor-derived DNAs, we identified somatic mutations that could inactivate this gene. However, we identified a prevalent germline single nucleotide variation at codon 50 (exon 3) of this gene [GCC (alanine) to TCC (serine)]. The GCC genotype was less prevalent in prostatic cancer patients in comparison to control subjects (P = 0.027) but no differences were seen with testicular, ovarian, and breast cancer. We also identified four genetic variations in exon 4, at codons106 [GGC (glycine) to GGA (glycine)], codon 112 [ACG (threonine) to ACC (threonine)], codon 141 [CTA (leucine) to CTG (leucine)], and at codon 149 [CCG (proline) to CTG (leucine)]. None of these variations was significantly different between normal subjects and cancer groups. We found no evidence for somatic mutations of the KLK10 gene in cancers of the prostate, breast, ovary, and testis. The single nucleotide variation at codon 50 appears to be associated with prostate cancer risk.


Respiratory disturbances in fibromyalgia: A systematic review and meta-analysis of case control studies.
Background: Fibromyalgia is a debilitating syndrome characterized by diffuse and chronic musculoskeletal pain.Objective: To perform a systematic review and meta-analysis of case-control studies to explore the respiratory disturbances among persons with fibromyalgia.Study appraisal and synthesis method: This review was performed in accordance with PRISMA guidelines (PROSPERO; identification number CRD: 42,020,196,835). We systematically searched seven electronic databases for articles published before December 2020.Eligibility criteria: Case-control studies comparing adults with fibromyalgia syndrome and healthy individuals with regard to the respiratory disturbances.Results: A total of six studies were included in the quantitative analysis. Pooled analysis showed that persons with fibromyalgia reported reduced chest expansion (MD -0.72, 95% CI, -1.70 to 0.27, I2 = 95%, p = 0.016), maximum expiratory pressure (MD -10.67, 95% CI, -18.62 to -2.72, I2 = 77%, p = 0.009), maximum inspiratory pressure (MD 11.04, 95% CI, -14.45 to -7.62, I2 = 0%, p < 0.001) and maximal voluntary ventilation (MD 11.79, 95% CI, -16.80 to -7.78, I2 = 0%, p < 0.001).Conclusion: Persons with fibromyalgia experience respiratory disturbances, such as reduced chest expansion, maximum expiratory pressure, maximum inspiratory pressure, and maximal voluntary ventilation.


Draft Genome Sequences of 11 Lactococcus lactis subsp. cremoris Strains.
The lactic acid bacterium Lactococcus lactis is widely used for the fermentation of dairy products. Here, we present the draft genome sequences of 11 L. lactis subsp. cremoris strains isolated from different environments.


The facet orientation circle. A new parameter for facet joint angulation in the lower lumbar spine.
A descriptive quantitative evaluation was done of the transverse orientation of the lower lumbar facet joints as measured by computed tomography scanning. To evaluate a new parameter for facet joint angulation in the transverse plane (the "facet orientation circle") and to obtain reference values for this new parameter. In other studies, both in vitro and in vivo, the angulation of the facet joints has been measured in degrees relative to the frontal or sagittal plane. These methods have some limitations. The parameter used in the present study has not been described in the literature. Lower lumbar facet joint orientation was measured in 212 vertebral levels of 123 consecutive patients using the facet orientation circle parameter. Patients with degenerative or developmental abnormalities of the lumbar spine were excluded, as were those with technically inadequate computed tomography studies. Mean facet orientation circle diameters (+/-SD) were: L3-L4, 43.7 +/- 10.5 mm; L4-L5, 63.8 +/- 26.4 mm; and L5-S1, 82.3 +/- 23.5 mm. Differences between right and left sides were: L3-L4, 6.3 +/- 7.1 mm; L4-L5, 13.9 +/- 25.3 mm; and L5-S1, 17.9 +/- 16.2 mm, intra-observer variability was 2.3%. Measurement of facet joint angulation using the facet orientation circle is possible and reproducible. The morphometric data presented may be useful as a reference for biomechanical and clinical research of facet joint orientation and asymmetry.


Bone-Inspired Tube Filling Decellularized Matrix of Toad Cartilage Provided an Osteoinductive Microenvironment for Mesenchymal Stem Cells to Facilitate the Radius Defect Repair of Rabbit.
Toad bone not only contains the rich cartilage-like matrix but also presents low immunogenicity. It is inferred that decellularized toad bone matrix (dBECM) may provide the more profitable osteoinductive microenvironment for mesenchymal stem cells (MSCs) to promote the repair of bone defects. Herein, a hollow bone-inspired tube is first made from hydroxyapatite (HA) and poly (γ-glutamic acid) (PGA), and then MSCs/dBECM hydrogel is uniformly filled to its central cavity, constructing a biomimetic bone (dBECM + MSCs - PGA + HA). In vitro scratch and transwell experiments show that dBECM hydrogel not only effectively promotes migration and proliferation of MSCs but also induces their osteogenic differentiation. Moreover, the less inflammatory macrophages infiltrate at rat skin after subcutaneously injecting dBECM hydrogel, indicating its low potential for inflammatory attack. After implanting dBECM + MSCs - PGA + HA to critical radius defect of rabbit, X-ray and CT imaging shows that the cortex is effectively regenerated and the medullary cavity recanalization is completed at 20 weeks. Moreover, the expression of Collagen-II and OCN are obviously increased in the defect after implanting dBECM + MSCs - PGA + HA. The therapeutic mechanism of dBECM + MSCs - PGA + HA scaffold are highly associated with the enhanced angiogenesis. Collectively, the biomimetic dBECM + MSCs - PGA + HA scaffold may be a promising strategy to improve radius defect healing efficiency.


Fluoroscopic-assisted laparoscopic retrieval of retained glucose sensor wire from the omentum.
We describe a case in which retained wires from a continuous glucose monitor were removed from the abdominal wall and peritoneum of a 6-year-old boy. We highlight a concern for continuous glucose monitor use in children and discuss surgical techniques used to retrieve tiny, mobile objects from complex body cavities.


Increased circulating CXCL13 levels in systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis.
CXC ligand 13 (CXCL13) is known as B cell chemotactic factor (BLC), promoting the migration of B lymphocytes by communicating with its receptor CXCR5, which can be regarded as part of pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This meta-analysis was to evaluate the circulating CXCL13 levels in SLE and RA. All articles were respectively gathered from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) (by the end of 10 April 2019). According to random effects model, standardized mean difference (SMD) and 95% confidence interval (CI) of CXCL13 levels in SLE and RA were calculated by Stata 12.0 software. Totally, 15 studies were selected (981 SLE patients and 380 healthy controls, 332 RA patients and 147 healthy controls). SLE and RA patients were significantly increased in circulating CXCL13 levels (SMD = 1.851, 95% CI 0.604-3.098; SMD = 1.801, 95% CI = 1.145-2.457). Subgroup analyses showed that SLE patients from the Chinese group and systemic lupus erythematosus disease activity index (SLEDAI) score ≥ 6 group had higher circulating CXCL13 levels (SMD = 2.182, 95% CI 0.135-4.229; SMD = 0.767, 95% CI 0.503-1.030). However, there were no significant changes in CXCL13 concentrations in SLE patients from the English and SLEDAI score < 6 group. Similarly, subgroup analyses presented that RA patients from different classifications showed higher circulating CXCL13 levels. There was no publication bias. This meta-analysis demonstrated increased circulating CXCL13 concentrations in SLE and RA patients. Circulating CXCL13 levels may act as biomarkers and therapy targets in the diagnosis and treatment of SLE and RA.Key Point• First, CXC ligand 13 (CXCL13) is closely related to the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), Second, this study may provide novel therapeutic targets for the treatment of SLE and RA patients. This meta-analysis provides a comprehensive analysis of circulating CXCL13 levels in patients with SLE and RA and also explores related influencing factors.


Characterizing the propagation path in moderate to strong optical turbulence.
In February 2005 a joint atmospheric propagation experiment was conducted between the Australian Defence Science and Technology Organisation and the University of Central Florida. A Gaussian beam was propagated along a horizontal 1500 m path near the ground. Scintillation was measured simultaneously at three receivers of diameters 1, 5, and 13 mm. Scintillation theory combined with a numerical scheme was used to infer the structure constant C2n, the inner scale l0, and the outer scale L0 from the optical measurements. At the same time, C2n measurements were taken by a commercial scintillometer, set up parallel to the optical path. The C2n values from the inferred scheme and the commercial scintillometer predict the same behavior, but the inferred scheme consistently gives slightly smaller C2n values.


Identifying nitrogen sources in intensive livestock farming watershed with swine excreta treatment facility using dual ammonium (δ15NNH4) and nitrate (δ15NNO3) nitrogen isotope ratios axes.
We proposed a novel approach based on dual ammonium and nitrate nitrogen isotope ratios (δ15NNH4 and δ15NNO3, respectively) axes to identify nitrogen sources in intensive livestock farming watersheds, especially those with swine excreta treatment facilities. The δ15NNH4 and δ15NNO3 values in water samples were measured monthly in 2016-2017. Soil and mineral fertilizers, sewage, sewage effluent, manure, and swine effluents were the five sources considered to identify nitrogen sources. The results showed that nitrogen pollution from agricultural activities was well reflected by the seasonal δ15NNH4 and δ15NNO3 patterns in the river, and microbial nitrification was suggested as the dominant nitrogen transformation process in the river. This study revealed that δ15NNH4 and δ15NNO3 axes provided better results than the traditionally used nitrate oxygen (δ18ONO3) and δ15NNO3 axes for identifying nitrogen sources in agricultural watersheds with swine excreta treatment facilities. The mixing model results showed that stream water was severely contaminated with swine effluents (e.g., a mean minimum contribution of 31%), thus affecting the quality of the mainstream (p = 0.068 < 0.10). This study was the first successful application of dual δ15NNH4 and δ15NNO3 axes to better understand nitrogen sources in intensive livestock farming watersheds with swine excreta treatment facilities.


Stimulation of insulin release from the MIN6 cell line by a new imidazoline compound, S-21663: evidence for the existence of a novel imidazoline site in beta cells.
1. The MIN6 cell line derived from in vivo immortalized insulin-secreting pancreatic beta cells was used to study the insulin-releasing capacity and the cellular mode of action of S-21663, a newly synthesized imadizoline compound known for its antidiabetic effect in vivo and its ability to release insulin from perfused pancreas. 2. S-21663, at concentrations ranging from 10(-5) M to 10(-3) M was able to release insulin from MIN6 cells; its activity peaked at 10(-4) M, a drop in the stimulant factor being noted between 10(-4) and 10(-3) M. Its efficacy, which did not differ whatever the glucose concentration (stimulant or not), was higher than that of the other secretagogues tested, glucose, sulphonylureas or the peptide tGLP-1. 3. In contrast to tGLP-1, S-21663 did not change the cyclic AMP content, whereas it increased Ca2+ influx via verapamil- and nifedipine-sensitive voltage-dependent calcium channels, the insulin release being a direct consequence of this Ca2+ entry. The S-21663-induced Ca2+ influx appears to be essentially the consequence of closure of K+ channels which differ from the ATP-dependent K+ (K-ATP) channels as determined by measurement of 86Rb efflux and use of a K-ATP channel opener. 4. Comparison of the effects of S-21663 to that of efaroxan, another imidazoline compound shown to act on insulin release in a glucose-dependent way via binding sites distinct from the imidazoline I1 and I2 sites, suggested that S-21663 acts through a novel site which displays a remarkably stable expression along the cell culture. 5. It is concluded that S-21663 is a very efficient, glucose-independent insulin secretagogue acting through a novel imidazoline site, linked to K+ channels, distinct from the I1, I2 and 'efaroxan' binding sites. In vitro and in vivo features of S-21663 indicate that this compound, or new drugs derived from it, might be the basis for a new pharmacological approach to the mangement of type II (non insulin-dependent) diabetes.


Unaccounted for anion in metabolic acidosis during severe sepsis in humans.
To quantitate the contribution of lactate, phosphate, urate, total serum proteins, and unidentified anions to the anion gap in patients with severe sepsis. Thirty critically ill patients with evidence of severe sepsis and systemic hypoperfusion were prospectively studied. The anion gap was calculated as [Na+] + [K+] - [Cl-] - [HCO3]. A corrected anion gap was calculated as the anion gap minus the anionic contribution of lactate, phosphate, urate, and total serum proteins. The corrected anion gap is a marker of unmeasured anion less unmeasured cation concentration. The mean anion gap was 21.8 +/- 1.4 mmol/L and the corrected anion gap was 3.7 +/- 0.8 mmol/L. The mean arterial blood lactate concentration was 5.9 +/- 0.8 mmol/L. The magnitude of the lactate concentration correlated linearly with the anion gap (r2 = .61, lactate = 0.4 anion gap - 3.9, n = 30, p less than .01). The corrected anion gap was greater than 0 in 24 (80%) of 30 patients. The magnitude of the corrected anion gap correlated linearly with the anion gap (r2 = .66, corrected anion gap = 0.5 anion gap - 6.3, n = 30, p less than .01). Since the slope of the regression line for estimating corrected anion gap from anion gap was 0.5, the contribution of unmeasured anions was as important as lactate in determining the anion gap. These data indicate that lactic acidosis does not entirely account for the metabolic acidosis during severe sepsis. Furthermore, the increased corrected anion gap suggests the presence of an unidentified anion (or anions) that is (or are) responsible, in large part, for the development of metabolic acidosis in patients with sepsis.


Singlet oxygen induced single-strand breaks in plasmid pBR322 DNA: the enhancing effect of thiols.
The biologically occurring thiols, glutathione, cysteamine and cysteine, significantly enhance the single-strand breaks in plasmid pBR322 DNA induced by singlet molecular oxygen (1O2) generated by the thermodissociation of the endoperoxide of 3,3'-(1,4-naphthylidene)dipropionate. The enhancing effect was also observed with chemically related sulfhydryl compounds but not by disulfides. In contrast, dihydrolipoate and its disulfide lipoate protected the plasmid DNA. Metal chelators as well as superoxide dismutase or catalase had no effect, whereas mannitol or sodium azide, decreased the thiol-1O2-induced strand breaks. It is concluded that the observed effects are mediated by reactive oxidation products arising from the 1O2-oxidation of thiols.


Urocanic acid suppresses induction of immunity in human skin.
Trans-urocanic acid is isomerized to cis-urocanic acid (C-UCA) by ultraviolet radiation. C-UCA suppresses immunity in vitro and in vivo in animals; its effect on human skin is unknown. We sought to determine whether its topical application to normal skin suppresses induction of immunity to dinitrochlorobenzene (DNCB). Forty subjects applied C-UCA (0%, 0.02%, 0.2%, or 2%) for 17 days. A 40-mcg dose of DNCB was then applied to induce immunity. Subjects were challenged for immunity at 6-week follow-up by occluding doses of DNCB (0, 3.125, 6.25, or 12.5 mcg) on untreated normal skin. Induced immunity was measured by area of erythema and induration 2 and 4 days postchallenge. No significant differences were found in incidence of sensitization by C-UCA concentration (P=.59). DNCB sensitization developed in all 10 subjects induced through 0% C-UCA (placebo); only 23 of 30 patients were sensitized through skin treated with C-UCA. Mean areas of erythema and induration induced through C-UCA-treated skin were less than those in controls (P < 0.05). The number of Langerhans cells in C-UCA-treated skin was unaffected. Laboratory tests of immune function and lymphocyte numbers were unchanged. Topically applied C-UCA blunts normal induction responses to a cutaneous sensitizer.


An fMRI investigation of a novel analogue to the Trail-Making Test.
The Trail-Making Test (TMT) is a widely used neuropsychological measure that assesses visuomotor abilities and cognitive flexibility. For the TMT-A condition participants are required to locate and connect numbers (i.e. 1-2-3…) while in the TMT-B condition participants perform the set-shifting task of locating and connecting numbers and letters (i.e. 1-A-2-B…). The TMT-B condition has shown impairments in many clinical populations, particularly schizophrenia patients, but the neurobiological underpinning of the task can be difficult to discern given pragmatic obstacles in adapting the task for neuroimaging. In a behavioural testing experiment we demonstrated a close correspondence between performance on the standard TMT and a novel, computer programmed adaptation of the TMT (pcTMT). The pcTMT was designed for functional magnetic resonance imaging (fMRI) administration and neuroimaging data for this task were obtained in. A whole brain analysis revealed significantly greater activation during the pcTMT-B relative to the pcTMT-A in right inferior/middle frontal cortices, right precentral gyrus, left angular gyrus/left middle temporal gyrus. These results identify the regions that most likely underlie cognitive flexibility during the TMT and are candidate regions underlying the impairment of groups with poor set-shifting abilities.


Perovskite synthesis, properties and their related biochemical and industrial application.
The perovskite structure is shown to be the single most versatile ceramic host. Inorganic perovskite type oxides are attractive compounds for varied applications due to its large number of compounds, they exhibit both physical and biochemical characteristics and their Nano-formulation have been utilized as catalysts in many reaction due to their sensitivity, unique long-term stability and anti-interference ability. Some perovskites materials are very hopeful applicants for the improvement of effective anodic catalysts performance. Depending Perovskite-phase metal oxides distinct variety of properties they became useful for various applications they are newly used in electrochemical sensing of alcohols, glucose, hydrogen peroxide, gases, and neurotransmitters. Perovskite organometallic halide showed efficient essential properties for photovoltaic solar cells. This review presents a full coverage of the structure, progress of perovskites and their related applications. Stress is focused particularly to different methods of perovskites properties and there related application.


Interaction of bifidobacteria with Caco-2 cells-adhesion and impact on expression profiles.
The aim of the present study was to study different strains of bifidobacteria for adhesion to Caco-2 intestinal epithelial cells (IECs) and to test for the mRNA response of these cells following interaction with bifidobacteria. Adhesion was tested at different pH conditions using model epithelia consisting of transwell cultures of fully differentiated Caco-2 cells. Microarrays were used to characterize changes in global expression profiles of Caco-2 cells co-cultured with peripheral blood mononuclear cells (PBMCs) and challenged with non-pathogenic Escherichia coli D2241 or four different strains of bifidobacteria. Furthermore, cytokine mRNA of IECs in responses to challenge with Bifidobacterium bifidum S17 or E. coli D2241 was tested in PBMC-sensitised Caco-2 cells using RT-PCR. Bifidobacteria showed strain-specific adhesion to Caco-2. Shift of apical pH from 7 to 4.5 resulted in strain-specific changes of adhesion. Global expression profiles of PBMC-sensitised Caco-2 cells revealed differential expression of a significant number of genes only after challenge with E. coli D2241 while cells were essentially unresponsive to challenge with four strains of bifidobacteria showing different adhesion properties. Using a RT-PCR approach, in the same system a similar differential expression after challenge with E. coli D2241 or B. bifidum S17 was observed for various immune markers. The presented results suggest that Caco-2 cells might be specifically unresponsive to challenge with bifidobacteria irrespective of the level of adhesion.


Coronary artery plaque burden does not affect left ventricular diastolic function in asymptomatic adults with normal ejection fraction.
Coronary artery disease (CAD) is commonly cited as a mechanism underlying diastolic dysfunction. However, the association of CAD without ischemia and left ventricular (LV) diastolic dysfunction has not been convincingly demonstrated in asymptomatic patients. The objective of this study was to determine if such a relation exists using coronary artery calcium score (CACS) as a surrogate for coronary atherosclerosis burden. Consecutive eligible patients with normal ejection fraction who underwent CACS assessment, echocardiography, and stress testing with negative results for obstructive CAD between August 2006 and September 2007 were included in this retrospective study. Clinical variables were collected from the medical record. Diastolic function classification was based on established echocardiographic guidelines recommended by the American Society of Echocardiography. Statistical analysis was used to identify predictors of CACS. A total of 349 subjects (302 men) aged 58 ± 6 years were studied. Risk factors included hyperlipidemia (n = 202 [58%]), hypertension (n = 127 [36%]), impaired fasting glucose (n = 78 [22%]), and diabetes (n = 21 [6%]). Left atrial volume index was weakly correlated with CACS (r = 0.26, P < .001). There was no significant relationship between CACS and LV diastolic function grade in the entire group (P = .14) or in a subgroup of younger patients (n = 140) who matched the ages qualifying for premature CAD (P = .17). After stepwise elimination multivariate analysis, five variables independently predicted CACS: age (P < .001), hyperlipidemia (P < .001), LA volume index (P < .001), male gender (P = .01), and LV posterior wall thickness (P = .03). In asymptomatic patients with normal LV ejection fraction and negative cardiac stress test results, CACS does not correlate with LV diastolic function as defined by established Doppler echocardiographic criteria. In the absence of ischemia, postinfarction LV remodeling, or previous coronary artery bypass surgery, CAD does not appear be a cause of LV diastolic dysfunction in asymptomatic patients.


Inhibition of naltrexone on relapse in methamphetamine self-administration and conditioned place preference in rats.
Methamphetamine (METH) addiction has been widely spread and caused severe problems both in society and public health in recent years, but there is a shortage of medication available. The naltrexone (NTX) as a non-selective opioid receptor antagonist has been widely applied to treat alcohol addiction and the relapse to opioid addiction after detoxification. In the present study, we investigated the potent pharmacotherapeutic effect of NTX in attenuating relapse to drug-seeking behavior in the METH self-administration and conditioned place preference (CPP) in rats. The results showed that acute intragastrical administration of NTX (40 mg/kg) significantly reduced cue-induced drug-seeking behavior after extinction training. The similar inhibition effect was observed in the CPP model, that the intragastrical administration of NTX (30 mg/kg) significantly disrupted the reactivation induced by intraperitoneal injection of METH (0.5 mg/kg) after the extinction training process. However, respective intragastrical administration of NTX (20 or 40 mg/kg) failed to alter the dose-response curve of METH under fixed ratio 2 program and intraperitoneal injection of METH (1.0 mg/kg)-induced reinstatement in rats self-administration. Overall, our findings suggest that NTX has the pharmacotherapeutic potential in reducing the relapse of METH addiction, which deserves further investigation as a promising medication for the treatment of METH addiction.


The healing process in normal canine arteries and in atherosclerotic monkey arteries after transluminal laser irradiation.
To evaluate the healing response of both normal and atherosclerotic arteries to laser radiation, 7 mongrel dogs and 4 hypercholesterolemic atherosclerotic monkeys underwent catheterization with a right Judkins catheter-optical fiber system designed to maximize arterial wall injury. Argon laser radiation was then delivered to the abdominal aorta and iliofemoral arteries. In the 11 animals, a total of 917 sites were irradiated in 33 arteries. Angiography did not reveal dissection or aneurysm formation; occlusive thrombosis was found in 2 arteries. Perforation of the arterial wall was a frequent complication. In animals killed between 1 hour and 4 days, light and electron microscopy of lased sites showed craters filled with a coagulum of blood and cellular debris with only a few adherent platelets. Healing occurred with a minimal inflammatory response and involved both fibroblasts and smooth muscle cells. Reendothelialization was seen in all animals killed between 7 and 14 days after lasing and was complete by 30 to 60 days. Within this period, no accelerated atherosclerosis was seen at lased sites in the hypercholesterolemic monkeys. It is concluded that transluminal lasing of normal arteries in dogs and in atherosclerotic arteries of monkeys is followed by healing and reendothelialization within a few weeks.


Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial.
Although percutaneous liver biopsy is a standard diagnostic procedure, it has drawbacks, including risk of serious complications. It is not known whether persons with advanced chronic liver disease have a greater risk of complications from liver biopsy than patients with more mild, chronic liver disease. The safety and complications of liver biopsy were examined in patients with hepatitis C-related bridging fibrosis or cirrhosis who were enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial. Standard case report forms from 2740 liver biopsies performed at 10 study sites between 2000 and 2006 were reviewed for serious adverse events, together with information from questionnaires completed by investigators about details of biopsy techniques used at each hospital. There were 29 serious adverse events (1.1%); the most common was bleeding (16 cases; 0.6%). There were no biopsy-related deaths. The bleeding rate was higher among patients with platelet counts of 60,000/mm(3) or less and among those with an international normalized ratio of 1.3 or greater, although none of the patients with an international normalized ratio greater than 1.5 bled. Excluding subjects with a platelet count of 60,000/mm(3) or less would have reduced the bleeding rate by 25% (4 of 16), eliminating only 2.8% (77 of 2740) of biopsies. Operator experience, the type of needle used, or the performance of the biopsy under ultrasound guidance did not influence the frequencies of adverse events. Approximately 0.5% of persons with hepatitis C and advanced fibrosis experienced potentially serious bleeding after liver biopsy; risk increased significantly in patients with platelet counts of 60,000/mm(3) or less.


Structure, process, and outcomes in skilled nursing facilities: understanding what happens to surgical patients when they cannot go home. A systematic review.
The surgical population is aging, and greater numbers of surgical patients are being discharged to skilled nursing facilities. Post-acute care is a poorly understood but very important aspect of our healthcare system. This systematic review examines the current body of literature surrounding the structural, process of care, and outcomes measurements for patients in skilled nursing facilities. English language articles published between 1998 and 2011 that purposed to examine nursing facility structure, process of care, and/or outcomes were included. Abstracts (2129) were screened and 102 articles were reviewed in full. Twenty-nine articles were included in the qualitative synthesis. The role of the care setting and care delivery in contributing to outcomes has not been well studied, and no strong conclusions can be made. This area of care currently represents a "black box" to practicing surgeons. An understanding of these factors maybe instrumental to determining future directions for research to maximize positive outcomes for these patients.


Effect of crude extracts of Moringa stenopetala and Artemisia absinthium on parasitaemia of mice infected with Trypanosoma congolense.
Treatment of trypanosomosis is currently facing a number of problems including toxicity of trypanocidal drugs and development of resistance by the parasites. These limitations have prompted the search for alternative active substances (such as of natural origin). The purpose of the study was to investigate the effect of extracts of Moringa stenopetala and Artemisia absinthium on Trypanosoma congolense in mice. Swiss white male mice aged 8-12 weeks were divided into six experimental groups of six animals. Water and methanol extracts of the two plants were prepared. T. congolense was isolated from cattle at Ghibe valley (Ethiopia). All experimental mice received approximately 1 x 10(5) trypanosomes in 0.2 ml of blood. Plant extracts were given orally to four groups (2 plant species and two extraction methods) at 400 mg/kg body weight for seven consecutive days. One group remained as distilled water treated control and the other as diminzene aceturate treated control. The effect of the extracts on levels of parasitaemia, body weight, packed cell volume (PCV) and mice survival was monitored for 25 days. All treatments have significantly reduced parasitaemia and helped improve body weight, PCV and survival of mice compared to the water-treated control (P < 0.01 in all cases). These effects were comparable to that with diminazene aceturate. No significant difference was observed in the reduction of parasitaemia between plant extract treatment groups. However, mice with extracts of A. absinthium had significantly higher body weight than those with extracts of M. stenopetala (P < 0.05). The two plants have antitrypanosomal potential against T. congolense by reducing the levels of parasitaemia, maintaining good PCV and body weight, and prolonging the lives of infected animals.


Unravelling the means to an end: RNA polymerase II transcription termination.
The pervasiveness of RNA synthesis in eukaryotes is largely the result of RNA polymerase II (Pol II)-mediated transcription, and termination of its activity is necessary to partition the genome and maintain the proper expression of neighbouring genes. Despite its ever-increasing biological significance, transcription termination remains one of the least understood processes in gene expression. However, recent mechanistic studies have revealed a striking convergence among several overlapping models of termination, including the poly(A)- and Sen1-dependent pathways, as well as new insights into the specificity of Pol II termination among its diverse gene targets. Broader knowledge of the role of Pol II carboxy-terminal domain phosphorylation in promoting alternative mechanisms of termination has also been gained.


Bis(1,10-phenanthroline-κN,N')[2-(4-sulfonato-anilino)acetato-κO]copper(II) dihydrate.
In the title compound, [Cu(C(8)H(7)NO(5)S)(C(12)H(8)N(2))(2)]·2H(2)O, the Cu(II) ion is coordinated by four N atoms from two 1,10-phenanthroline (phen) ligands and one O atom from a 2-(4-sulfonato-anilino)acetate (spia) ligand in a distorted square-pyramidal geometry. Inter-molecular N-H⋯O and O-H⋯O hydrogen bonds, as well as π-π inter-actions between phen ligands and between phen and spia ligands [centroid-centroid distances = 3.663 (3), 3.768 (3) and 3.565 (3) Å], result in a three-dimensional supra-molecular structure.


Adolescent Popularity: Distinct Profiles and Associations with Excessive Internet Usage and Interpersonal Sensitivity.
Peer popularity constitutes a pivotal developmental task to adolescents' current and future adaptation. This study identified distinct adolescent popularity profiles and explored their links with excessive Internet usage and interpersonal sensitivity. The sample included 2090 students attending Greek high schools (Mage = 16.16, SD = 0.91). Their popularity was measured via self-report and peer sociometric means. They also responded to the Internet Addiction Test (IAT) and the Interpersonal Sensitivity subscale of the Symptom Checklist-90-Revised (SCL-90-R). A sequence of latent profile analysis, ANOVAs and linear regression models were performed. Three distinct popularity profiles were revealed: the "Average Confident" (68.4%), the "Socially Vulnerable" (26.8%), and the "Insecure Bi-Strategic" (4.8%). These profiles did not significantly vary regarding their Internet usage and interpersonal sensitivity behaviours. Interestingly, lower self-perceived popularity predicted higher interpersonal sensitivity, whereas higher actual popularity predicted excessive Internet use. Findings have important implications for student-tailored mental health prevention and intervention practices.


Parental stress and dental caries experience in adolescents: analysis of data from a birth cohort study in Pelotas, Southern Brazil.
Analyze the association between parental stress and dental caries experience in adolescents in southern Brazil using data from the Pelotas 2004 Birth Cohort. Interviews and oral health examinations for the determination of the main exposure and outcome of the study were performed in the homes of the adolescents. The outcome was dental caries experience in the permanent dentition analyzed using the Decayed, Missing and Filling Surfaces (DMFS) index. The main exposure was parental stress measured using the Parenting Stress Index-Short Form administered to the parents of the adolescents. Demographic/socioeconomic characteristics, oral health characteristics and oral health-related quality of life were considered potential confounding factors. Negative binomial regressions estimated mean ratios (MR) and 95% confidence intervals (CI). Nine hundred ninety-six adolescents were evaluated at 12 and 13 years of age. The prevalence of dental caries experience in the adolescents was 36.9% (95% CI: 33.8-40.0) and 15.1% (95% CI: 12.8-17.3) of the parents had parental stress. After adjusting for confounding factors, parental stress was associated with a higher mean number of decayed, missing and filling surfaces in the adolescents (MR = 1.10; 95% CI: 1.01-1.26; p = 0.045). Adolescents of parents with parental stress have more dental caries experience compared to those whose parents do not have parental stress.


Mining Migrant Worker Recruitment Policy and the Production of a Silicosis Epidemic in Late 20th-Century Southern Africa.
Between the 1980s and 2000s, an epidemic of silicosis was identified in migrant black gold miners, many from neighbouring countries, who had worked in the South African gold mines. This study uses the newly available employment database of a large gold mining company to demonstrate how a sustained rise in employment duration in a new cohort of black migrant workers resulted from changes in recruitment policy, and it examines the implications for current surveillance and redress. Contract data of 300,774 workers from the employment database of a multi-mine gold mining company were analysed for 1973-2018. Piecewise linear regression was applied to determine trends in cumulative employment, including South African versus cross-border miners. The proportions with cumulative employment of at least 10, 15, or 20 years, typical thresholds for chronic silicosis, were also calculated. Five calendar phases were identified between 1973 and 2018. During the second phase, 1985-2013, mean cumulative duration of employment rose fivefold, from 4 to 20 years. Cumulative employment continued to rise, although more slowly, before peaking in 2014 at 23.5 years and falling thereafter to 20.1 years in 2018. Over most of the 1973-2018 period, miners from neighbouring countries had greater cumulative employment than South African miners. Overall, the proportion of miners exiting with at least 15 years of cumulative employment rose from 5% in 1988 to 75% in 2018. This report identifies a number of fundamental changes in labour recruitment policy in the gold mining industry in the 1970s which provide an explanation for the subsequent rise in cumulative exposure and associated silicosis risk. These new data support the hypothesis of a silicosis epidemic driven by increasing cumulative silica dust exposure in a new cohort of circular migrant workers from the 1970s. They inform current programmes to improve surveillance of this neglected population for silicosis and related disease and to provide medical examinations and compensation to a large number of former gold mines. The analysis highlights the lack of information on cumulative employment and silicosis risk among migrant miners in previous decades. The findings have global relevance to the plight of such migrant workers in hazardous occupations.