Mesenchymal stem cells enhance autophagy and increase β-amyloid clearance in Alzheimer disease models.
Current evidence suggests a central role for autophagy in Alzheimer disease (AD), and dysfunction in the autophagic system may lead to amyloid-β (Aβ) accumulation. Using in vitro and in vivo AD models, the present study investigated whether mesenchymal stem cells (MSCs) could enhance autophagy and thus exert a neuroprotective effect through modulation of Aβ clearance In Aβ-treated neuronal cells, MSCs increased cellular viability and enhanced LC3-II expression compared with cells treated with Aβ only. Immunofluorescence revealed that MSC coculture in Aβ-treated neuronal cells increased the number of LC3-II-positive autophagosomes that were colocalized with a lysosomal marker. Ultrastructural analysis revealed that most autophagic vacuoles (AVs) in Aβ-treated cells were not fused with lysosomes, whereas a large portion of autophagosomes were conjoined with lysosomes in MSCs cocultured with Aβ-treated neuronal cells. Furthermore, MSC coculture markedly increased Aβ immunoreactivity colocalized within lysosomes and decreased intracellular Aβ levels compared with Aβ-treated cells. In Aβ-treated animals, MSC administration significantly increased autophagosome induction, final maturation of late AVs, and fusion with lysosomes. Moreover, MSC administration significantly reduced the level of Aβ in the hippocampus, which was elevated in Aβ-treated mice, concomitant with increased survival of hippocampal neurons. Finally, MSC coculture upregulated BECN1/Beclin 1 expression in AD models. These results suggest that MSCs significantly enhance autolysosome formation and clearance of Aβ in AD models, which may lead to increased neuronal survival against Aβ toxicity. Modulation of the autophagy pathway to repair the damaged AD brain using MSCs would have a significant impact on future strategies for AD treatment.


Enzymatically catalyzed CO2 -H2 O equilibration for oxygen isotope analyses of aqueous samples.
The classic CO2 -H2 O equilibration method is a very popular technique for the measurement of the oxygen isotope composition of aqueous samples in stable isotope geochemistry. This study examined whether enzymatically controlled CO2 -H2 O equilibration by carbonic anhydrase (CA) could reduce the time for oxygen isotope equilibrium between CO2 and H2 O at 25°C. Four types of aqueous samples containing CA were equilibrated with CO2 gases using a continuous flow isotope ratio mass spectrometer equipped with an automated gas sample collection device. We examined the effect of CA concentration in an aqueous sample, the influence of drying technique for the preparation of sample vials containing dried CA, the age of CA stock solution, and the ionic strength and the oxygen isotope composition of aqueous samples. CA rapidly catalyzed the oxygen isotope exchange between CO2 and H2 O and was unaffected by drying technique or stock solution age. Compared with aqueous samples with no CA or 0.2 μmolal CA, samples containing 4 μmolal CA significantly reduced the CO2 -H2 O equilibration time for deionized water and artificial seawater (ionic strength = ~0.6) from ~19 h and ~23 h to ~0.30 h and ~0.77 h, respectively at 25°C. This enzymatically catalyzed CO2 -H2 O equilibration method is time-efficient, cost-effective, requires no additional data correction procedure, and can be used for most commercially available CO2 -H2 O equilibration devices without any modification.


Growth deceleration and bone metabolism in nutritional dwarfing rats.
Nutritional status as well as energy and protein intake are critical regulators of IGF-1 and IGFBP-3 and contribute to the modulation of bone remodeling and formation. The purpose of this study was to investigate on an experimental model with nutritional dwarfing (ND), whether the alterations on body growth velocity, energy metabolism and body composition could affect serum concentrations of IGF-1 and IGFBP-3 and bone (tibiae and mandible) histology and histomorphometry. Twenty-one male weanling Wistar rats (body weight = 38.20 +/- 0.94 g) were randomized to three groups: seven of them were killed at day = 0 (CO, n = 7); control (C, n = 7); and experimental 80 (E80, n = 7). During 4 weeks, C was fed ad libitum with a 1:1 carbohydrate to fat diet. E80 was being underfed with the same diet by 80% and the following parameters were measured: weight (Wt) for length (L) ratio z-score; oxygen consumption (VO2); body composition (BC) by EM-SCAN SA 3000. At t = 28, E80 and C were killed. Serum IGF-1 and IGFBP-3 and bone histology and histomorphometry were performed on C0, E80 and C. E80 showed Wt for L z-score between lean and adequate, a decrease in VO2 according to body proportions, a BC of a delayed puberty individual, IGF-1 and IGFBP-3 decreased by 56 and 53%, respectively. Tibiae's hematopoyetic and adipose bone marrow areas were combined, with sealing trabeculae on metaphyseal areas. This study suggests that there is a relationship among growth deceleration in ND rats and structural alterations on tibiae.


Effect of mannan oligosaccharides and fructan on growth performance, nutrient digestibility, blood profile, and diarrhea score in weanling pigs.
A total of 150 weanling pigs [(Yorkshire × Landrace) × Duroc] with an average BW of 7.22 ± 0.80 kg (21 d of age) were used in a 28-d trial to determine the effects of dietary fructan and mannan oligosaccharides on growth performance, nutrient digestibility, blood profile, and diarrhea score in weanling pigs. Pigs were allotted randomly to 1 of 5 dietary treatments: 1) negative control (NC), basal diet; 2) positive control (PC), NC + 0.01% apramycin (165 mg/kg); 3) NC + 0.1% fructan (FC); 4) NC + 0.1% mannan oligosaccharide source (MO); and 5) NC + 0.05% fructan + 0.05% mannan oligosaccharide source (FM). There were 3 replications per treatment with 10 pigs per pen (5 barrows and 5 gilts). From d 0 to 14, ADG and ADFI of pigs fed the PC, MO, and FM diets were greater (P < 0.05) than pigs fed the NC diet. From d 15 to 28, there were no differences (P > 0.05) in ADG, ADFI, and G:F. During the overall period (d 0 to 28), pigs fed the MO diet had a greater ADG than pigs fed the NC diet (P < 0.05). Pigs fed the PC and MO diets increased ADFI (P < 0.05) compared with pigs fed the NC diet. However, no differences were detected among dietary treatments in G:F during the overall experimental period. On d 14, the apparent total tract digestibility (ATTD) of DM and N in pigs fed the PC, MO, and FM diets was greater (P < 0.05) than pigs fed the NC diet. The ATTD of DM increased (P < 0.05) in pigs fed the MO and FM diets compared with pigs fed the FC diet. However, at the end of the experiment, pigs fed the FM diet had a greater (P < 0.05) ATTD of DM compared with pigs fed the NC diet. Additionally, there were no differences in IgG, red blood cells, white blood cells, and lymphocyte counts among dietary treatments on d 0, 14, or 28. The diarrhea score in pigs fed the MO diet was reduced (P < 0.05) compared with pigs fed the NC diet. In conclusion, mannan oligosaccharides have a beneficial effect on growth performance and nutrient digestibility in weanling pigs. Furthermore, mannan oligosaccharides can decrease diarrhea score in weanling pigs.


Inhibitory effects of andrographolide on migration and invasion in human non-small cell lung cancer A549 cells via down-regulation of PI3K/Akt signaling pathway.
Lung cancer is the leading cause of death among cancers worldwide and non-small cell lung cancer (NSCLC) comprises more than 80% of lung cancer cases. Treatment options for patients with advanced NSCLC have evolved in the last decade with the advent of novel biological agents. Andrographolide, a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to have the potential to be developed as a chemotherapeutic agent. In order to understand the anti-cancer properties of andrographolide, we examined its effect on migration and invasion in human NSCLC A549 cells. The results of wound-healing assay and in vitro transwell assay revealed that andrographolide inhibited dose-dependently the migration and invasion of A549 cells under non-cytotoxic concentrations. Molecular data showed that the effect of andrographolide in A549 cells might be mediated via sustained inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt signal involved in the up-regulation of matrix metalloproteinases (MMPs). Our results showed that andrographolide exerted an inhibitory effect on the activity and the mRNA and protein levels of MMP-7, but not MMP-2 or MMP-9. The andrographolide-inhibited MMP-7 expression or activity appeared to occur via activator protein-1 (AP-1) because of its DNA binding activity was suppressed by andrographolide. Additionally, the transfection of Akt over-expression vector (Akt1 cDNA) to A549 cells could result in an increase expression of MMP-7 concomitantly with a marked induction on cell invasion. These findings suggested that the inhibition on MMP-7 expression by andrographolide may be through suppression on PI3K/Akt/AP-1 signaling pathway, which in turn led to the reduced invasiveness of the cancer cells.


Sodium-lithium countertransport genotype and the probability of hypertension in adults.
The objective of the present study was to determine whether information about a biometrically inferred single gene with large effects on erythrocyte sodium-lithium countertransport is useful in predicting the probability of having hypertension. We used multivariate logistic regression to model the relationship between the probability of having hypertension and predictor traits in a sample of 382 unrelated adult women and 347 unrelated adult men from Rochester, Minn. First, we identified a set of demographic, biochemical, and physiological predictors. Second, we analyzed whether the relationship between the probability of having hypertension and the identified predictor traits was heterogeneous between the biometrically inferred single locus genotypes with large effects on sodium-lithium countertransport level. Third, if there was no heterogeneity, we assessed whether sodium-lithium countertransport genotypes made an additional contribution to predicting the probability of having hypertension after other predictors were considered. In women, the predictors of the probability of having hypertension were age, plasma apolipoprotein CIII, body mass index, and an interaction term involving age and body mass index. The relationship between the probability of having hypertension and the identified predictors was not heterogeneous between sodium-lithium countertransport genotypes, and genotype did not contribute to the prediction of the probability of having hypertension after the identified predictors were considered. In men, predictors of the probability of having hypertension were age, plasma levels of high-density lipoprotein cholesterol, apolipoproteins AI and CII, sodium-lithium countertransport level, and sodium-lithium countertransport genotype. The relationship between the probability of having hypertension and sodium-lithium countertransport level and age were heterogeneous between biometrically inferred sodium-lithium countertransport genotypes.(ABSTRACT TRUNCATED AT 250 WORDS)


The complete chloroplast genome sequence of Corylopsis sinensis (Hamamelidaceae).
Corylopsis sinensis Hemsl. is a deciduous shrub endemic to China, which is a valuable medicinal and ornamental species. In this study, we report the complete chloroplast genome sequence of C. sinensis, providing a genomic basis for future research. The chloroplast genome is 159,419 base pairs (bp) in length, with a large single-copy (LSC) region of 88,152 bp, a small single-copy (SSC) region of of 18,701 bp, and two inverted repeat (IR) regions of 26,283 bp. The overall GC content is 38.0% and the chloroplast genome encodes 113 unique genes including 79 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. The phylogenetic results show that C. sinensis is sister to C. spicata. These results of C. sinensis will improve our understanding of the evolution of Corylopsis and Hamamelidaceae.


Decreased Functional Connectivities of Low-Degree Level Rich Club Organization and Caudate in Post-stroke Cognitive Impairment Based on Resting-State fMRI and Radiomics Features.
Stroke is an important cause of cognitive impairment. Rich club organization, a highly interconnected network brain core region, is closely related to cognition. We hypothesized that the disturbance of rich club organization exists in patients with post-stroke cognitive impairment (PSCI). We collected data on resting-state functional magnetic resonance imaging (rs-fMRI) with 21 healthy controls (HC), 16 hemorrhagic stroke (hPSCI), and 21 infarct stroke (iPSCI). 3D shape features and first-order statistics of stroke lesions were extracted using 3D slicer software. Additionally, we assessed cognitive function using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Normalized rich club coefficients were higher in hPSCI and iPSCI than HC at low-degree k-levels (k = 1-8 in iPSCI, k = 2-8 in hPSCI). Feeder and local connections were significantly decreased in PSCI patients versus HC, mainly distributed in salience network (SN), default-mode network (DMN), cerebellum network (CN), and orbitofrontal cortex (ORB), especially involving the right and left caudate with changed nodal efficiency. The feeder and local connections of significantly between-group difference were positively related to MMSE and MoCA scores, primarily distributed in the sensorimotor network (SMN) and visual network (VN) in hPSCI, SN, and DMN in iPSCI. Additionally, decreased local connections and low-degree ϕnorm(k) were correlated to 3D shape features and first-order statistics of stroke lesions. This study reveals the disrupted low-degree level rich club organization and relatively preserved functional core network in PSCI patients. Decreased feeder and local connections in cognition-related networks (DMN, SN, CN, and ORB), particularly involving the caudate nucleus, may offer insight into pathological mechanism of PSCI patients. The shape and signal features of stroke lesions may provide an essential clue for the damage of functional connectivity and the whole brain networks.


Toxicology cart for stocking sufficient supplies of poisoning antidotes.
Within a three-month period, the University of New Mexico Health Sciences Center (UNMHSC) encountered three toxicological emergencies in which antidotes were either unavailable or inadequately stocked. Patient A was a patient with ethylene glycol intoxication. The emergency department (ED) physician ordered a 10% ethanol infusion. The pharmacy staff was unable to locate the commercially available solution and had to compound the infusion, resulting in a delay in administration of the antidote. Patient B was a patient at an outside hospital with organophosphate exposure whose transfer to our ED was requested by the other hospital. The pharmacy staff was unable to locate the pralidoxime needed to treat this patient; therefore; the patient was not transferred. It was later discovered that the pralidoxime had been stored in a location inconsistent with the storage policy for this medication. Patient C was a patient with severe rattlesnake envenomation. The pharmacy staff could locate only half of the antivenin needed to treat this patient. In each of these three cases, it was necessary to compound the required medication or to obtain it from other local facilities. These cases underscore the need for pharmacies to stock adequate amounts of poisoning antidotes in one immediately accessible location. A similar problem with understocking of poisoning antidotes exists throughout the United States.


[Recent advances in gastrointestinal hormones].
Recent advances in the field of peptide chemistry and gene technology have resulted in an explosive accumulation of information on the chemical structures of gastrointestinal hormones. Based on the information, chemical syntheses of these peptides or their shorter fragments and analogs have been performed. Synthetic peptides related to the hormones have now become important tools in searching for functions of peptides and in producing region-specific antisera to the respective peptides. Using these antisera, hormone-producing cells were clearly identified and the post-translational biosynthetic processings in the cells were demonstrated. Recent immunohistochemical studies have also revealed that cells contain and can release a variety of peptides or amines that are capable of influencing target cells and acting as hormone, neurotransmitter or neuromodulator. In addition, recent studies on galanin and glucagon-like peptide-1 (GLP-1) are described.


[Cytochemical methodology applied to the study of staining mechanisms and fluorescence of nucleic acids].
The intercalation of the corresponding product in the DNA molecule is related to activity of some anti-neoplastic antibiotics, and to chemical carcinogenesis and mutagenesis. DNA-intercalating agents may inhibit replication and/or transcription, and stop cell proliferation. This work deals with the mechanisms of staining and fluorescence, and with the intercalative binding of some cationic dyes. It is shown that chromatin fluorescence depends on the product concentration, it is not modified by nitrites, molibdate or inorganic cations, but it is inhibited by non-fluorescent intercalating substances such as caffeine and o-phenanthroline. The results suggest the existence of intercalative binding. Contrarily, chromatin staining is related to electrostatic binding with DNA.


Molecular evolution and transcriptional regulation of the oilseed rape proline dehydrogenase genes suggest distinct roles of proline catabolism during development.
Six BnaProDH1 and two BnaProDH2 genes were identified in Brassica napus genome. The BnaProDH1 genes are mainly expressed in pollen and roots' organs while BnaProDH2 gene expression is associated with leaf vascular tissues at senescence. Proline dehydrogenase (ProDH) catalyzes the first step in the catabolism of proline. The ProDH gene family in oilseed rape (Brassica napus) was characterized and compared to other Brassicaceae ProDH sequences to establish the phylogenetic relationships between genes. Six BnaProDH1 genes and two BnaProDH2 genes were identified in the B. napus genome. Expression of the three paralogous pairs of BnaProDH1 genes and the two homoeologous BnaProDH2 genes was measured by real-time quantitative RT-PCR in plants at vegetative and reproductive stages. The BnaProDH2 genes are specifically expressed in vasculature in an age-dependent manner, while BnaProDH1 genes are strongly expressed in pollen grains and roots. Compared to the abundant expression of BnaProDH1, the overall expression of BnaProDH2 is low except in roots and senescent leaves. The BnaProDH1 paralogs showed different levels of expression with BnaA&C.ProDH1.a the most strongly expressed and BnaA&C.ProDH1.c the least. The promoters of two BnaProDH1 and two BnaProDH2 genes were fused with uidA reporter gene (GUS) to characterize organ and tissue expression profiles in transformed B. napus plants. The transformants with promoters from different genes showed contrasting patterns of GUS activity, which corresponded to the spatial expression of their respective transcripts. ProDHs probably have non-redundant functions in different organs and at different phenological stages. In terms of molecular evolution, all BnaProDH sequences appear to have undergone strong purifying selection and some copies are becoming subfunctionalized. This detailed description of oilseed rape ProDH genes provides new elements to investigate the function of proline metabolism in plant development.


Hemorrhagic complications of thrombolytic therapy.
Thrombolytic therapy salvages ischemic myocardium by rapidly reestablishing coronary artery patency in acute myocardial infarction. One of its major limitations is the complication of hemorrhage. A retrospective study of myocardial infarction patients who received thrombolytic therapy was performed to determine risk factors associated with a hemorrhagic event. Three hundred fifty patients were enrolled, and 20 (5.7%) had a bleeding complication, including four patients (1.1%) who had an intracranial hemorrhage. The factors associated with an increased risk for a significant hemorrhagic event were age (> 65 years) and female gender. Factors associated with an intracranial hemorrhage were age (> 65 years) and a history of hypertension.


Squamous differentiation and cytokeratin expression in an osteosarcoma: a case report and review of the literature.
Cytokeratin expression has been documented in a variety of sarcomas including synovial sarcomas, epithelioid sarcomas, Ewing's sarcomas and, rarely, osteosarcomas. In osteosarcomas immunohistochemically shown to expression cytokeratins, a component of epithelioid cells is generally present. These epithelioid cytokeratin positive cells raise the possibility of metastatic disease with prognostic and therapeutic implications differing from primary osteosarcoma. The cytokeratin-expressing cells of the cases reported in the literature have not shown definitive squamous differentiation with keratin pearl formation. We report a case of osteosarcoma in which islands of malignant squamous cells were present showing keratin pearl formation and expression of cytokeratins.


Competitive repopulation assay of two gene-marked cord blood units in NOD/SCID/gammac(null) mice.
In multiunit cord blood transplantation, hematopoietic stem cells from each unrelated cord blood (UCB) unit competitively reconstitute the hematopoietic system in a recipient. To evaluate the fate of the progeny of each UCB unit and to determine the effects of graft-versus-graft reaction, we established a novel competitive repopulation assay using NOD/SCID/gammac(null) mice in which human T lymphocytes develop from CD34+ cells. CD34+ cells from each UCB unit were labeled with recombinant lentivirus vectors carrying genes encoding either enhanced green fluorescent protein (EGFP) or enhanced yellow fluorescent protein (EYFP). Hematopoietic chimerism composed of both EGFP+ and EYFP+ cells was stably maintained up to 6 months after transplantation with purified CD34+ cells; the ratio of EGFP+ to EYFP+ cells in peripheral blood and bone marrow posttransplantation was equivalent to the ratio of these cells at transplantation. However, when mononuclear cells from two UCB units were cotransplanted with CD34+ cells, engraftment was highly competitive, with cells from only one or the other of the two UCB units surviving. Further subfractionations of mononuclear cells indicate that the skewed chimerism that is often observed in clinical multiunit cord blood transplantation may be mediated by the cooperation of both CD4+ and CD8+ T cells. The assay established here will be a useful tool for analyzing hematopoietic reconstitution in clinical multiunit cord blood transplantation.


Prevalence of the molecular marker of Plasmodium falciparum resistance to chloroquine and sulphadoxine/pyrimethamine in Benin seven years after the change of malaria treatment policy.
In Benin, the National Malaria Control Programme (NMCP) changed the policy of malaria treatment in 2004 following increasing of failure rate of treatment with chloroquine (CQ) and sulphadoxine-pyrimethamine (SP). The objective of this study was to determinate the prevalence of Plasmodium falciparum molecular markers that are associated with resistance to CQ and SP in Benin seven years after the new policy was instituted. The study was conducted in southern Benin, a region characterized by a perennial malaria transmission. Blood samples were collected in 2011 from children presenting with symptomatic and asymptomatic P. falciparum infections and living in the same area. The prevalence of critical point mutations in the genes of pfcrt (codon 76), pfmdr1 (codon 86), pfdhfr (codons, 51, 59 and 108) and pfdhps (codons 437, 540) was examined in parasite isolates by mutation-specific restriction enzyme digestion of nested PCR products. A high prevalence of parasites carrying point mutations in all studied targets was found: T76: 93.9% [89.8; 96.7], I51: 96.2% [92.7; 98.4], R59: 93, 9% [89.7; 96.7], N108: 97.6% [94.6; 99.2] and G437: 71.4% [64.8; 77.4]. No mutation was found at codon 540 of the pfdhps gene. The proportion of parasite isolates carrying triple mutation in the pfdhfr gene IRN (I51, R59 andN108) and quadruple mutation on the combination of pfdhfr/pfdhps IRNG (I51, R59, N108 and G437) was 91.5% [86.9; 94.9] and 65.7% [58.9; 72.1], respectively. Analysis of mutation in relation to the clinical status (symptomatic or asymptomatic) and according to age (younger or older than 10 years) showed similar very high frequencies in each category without significant difference between two groups. These results suggest a persistence level of resistance of P. falciparum to CQ and SP, seven years after the recommendation of the change of malaria treatment policy in Benin. The distribution of mutations studied was neither related to age nor to clinical status.


Citrate lyase from Klebsiella pneumoniae. The complete primary structure of the acyl lyase subunit.
The primary structure of the beta-subunit (acyl lyase subunit) of citrate lyase from Klebsiella pneumoniae (ATCC 13,882) was determined with protein chemical methods. The polypeptide chain consists of 289 amino acid residues and has a molecular mass of 31,352 Da. The two half-cystine residues of the subunit are present as cysteines and not involved in disulfide bridges. The sequence shows no homology to known sequences of proteins or nucleic acids and reads (sequence; see text)


An apparent angle dependence for the nonradiative deactivation of excited triplet states of sterically constrained, binuclear ruthenium(II) bis(2,2':6',2' '-terpyridine) complexes.
The photophysical properties are reported for a series of binuclear ruthenium(II) bis(2,2':6',2"-terpyridine) complexes built around a geometrically constrained, biphenyl-based bridge. The luminescence quantum yield and lifetime increase progressively with decreasing temperature, but the derived rate constant for nonradiative decay of the lowest-energy triplet state depends on the length of a tethering strap attached at the 2,2'-positions of the biphenyl unit. Since the length of the strap determines the dihedral angle for the central C-C bond, the rate of nonradiative decay shows a pronounced dependence on angle. The minimum rate of nonradiative decay occurs when the dihedral angle is 90 degrees, but there is a maximum in the rate when the dihedral angle is about 45 degrees. This effect does not appear to be related to the extent of electron delocalization at the triplet level but can be explained in terms of variable coupling with a low-frequency vibrational mode associated with the strapped biphenyl unit.


[In vivo assessment of bone union by means of monitoring bone healing].
Basing on personal clinical experiences and available literature I assumed that the more advanced bone union is, the less important the role of stabilizing instruments in load transfer. At the same time the importance of bone consolidation increases. Material consisted of 46 operated patients, who had been treated with an external Zespol fixator. To assess load inversion a special measuring instrument was constructed. It was found that both the type of osteosynthesis and kind of fracture influenced the load inversion process. Neutralizing stabilization (group C) gave the shortest bone union time i.e. 22.6 weeks Average bone union time in contact stabilization was 34.4 and 30.1 weeks, depending on fracture type.


Force-Velocity Relationship in the Countermovement Jump Exercise Assessed by Different Measurement Methods.
This study aimed to compare force, velocity, and power output collected under different loads, as well as the force-velocity (F-V) relationship between three measurement methods. Thirteen male judokas were tested under four loading conditions (20, 40, 60, and 80 kg) in the countermovement jump (CMJ) exercise, while mechanical output data were collected by three measurement methods: the Samozino's method (SAM), a force platform (FP), and a linear velocity transducer (LVT). The variables of the linear F-V relationship (maximum force [F0], maximum velocity [V0], F-V slope, and maximum power [P0]) were determined. The results revealed that (1) the LVT overestimated the mechanical output as compared to the SAM and FP methods, especially under light loading conditions, (2) the SAM provided the lowest magnitude for all mechanical output, (3) the F-V relationships were highly linear either for the SAM (r = 0.99), FP (r = 0.97), and LVT (r = 0.96) methods, (4) the F-V slope obtained by the LVT differed with respect to the other methods due to a larger V0 (5.28 ± 1.48 m·s-1) compared to the SAM (2.98 ± 0.64 m·s-1) and FP (3.06 ± 0.42 m·s-1), and (5) the methods were significantly correlated for F0 and P0, but not for V0 or F-V slope. These results only support the accuracy of the SAM and FP to determine the F-V relationship during the CMJ exercise. The very large correlations of the SAM and LVT methods with respect to the FP (presumed gold-standard) for the mean values of force, velocity and power support their concurrent validity for the assessment of mechanical output under individual loads.


Usefulness of short-lived proteins as nutritional indicators surgical patients.
Biochemical indicators are used to assess the adequacy of nutritional support given to postoperative patients. However, the metabolic alterations present in these patients diminish the efficiency of these indicators. The objective of this work is to determine the usefulness of short-lived proteins as indicators to assess the nutritional support administered to patients during the metabolic stress phase produced by surgery. The nitrogen balance and plasma concentrations of transthyretin, retinol binding protein, and insulin-like growth factor-1 were determined in 24 patients who received 4 different nutritional regimens during 7 days after surgery. Transthyretin and retinol binding protein, although sensitive to nutritional intake (P<0.0005 and P<0.04 respectively), were strongly affected by the stress response (P<0.008 and P<0.0003 respectively), thus limiting their usefulness for nutrition assessment. Insulin-like growth factor-1 was not influenced by the stress response and was sensitive to the nutritional supply (P<0.0001). Insulin-like growth factor-1 was the only component that showed similar efficiency than nitrogen balance as nutritional indicator. Transthyretin and retinol binding protein are not adequate to assess the nutritional supply during the stress phase after surgery, while insulin-like growth factor-1 is a suitable indicator of the adequacy of recent intake in this situation, similar in performance to nitrogen balance.


Residues of Cardiovascular and Lipid-Lowering Drugs Pose a Risk to the Aquatic Ecosystem despite a High Wastewater Treatment Ratio in the Megacity Shanghai, China.
The residues of pharmaceuticals in surface waters of megacities and ecotoxicological implications are of particular concern. In this study, we combined field investigations and model simulations to explore the contamination of cardiovascular and lipid-lowering drugs, one group of the most prescribed medications globally, in surface waters of a typical megacity, Shanghai, with a high wastewater treatment ratio (≈96%). Among 26 target substances, 19 drugs were detected with aqueous concentrations ranging from 0.2 (ketanserin) to 715 ng/L (telmisartan). Of them, angiotensin II receptor antagonists, telmisartan and irbesartan, were dominant besides β-blockers. Spatial distribution analysis demonstrated their much higher levels in tributaries compared to the mainstream. The results of model simulations and field investigation revealed relatively low concentrations of cardiovascular and lipid-lowering drugs in surface waters of Shanghai compared to other cities in highly developed countries, which is associated with low per capita usage in China. Ecotoxicological studies in zebrafish embryos further revealed developmental effects, including altered hatching success and heart rate, by irbesartan, telmisartan, lidocaine, and their mixtures at ng/L concentrations, which are typical levels in surface waters. Overall, the present results suggest that the high wastewater treatment ratio was not sufficient to protect fish species in the aquatic ecosystem of Shanghai. Exposure to cardiovascular and lipid-lowering drugs and associated risks will further increase in the future due to healthcare improvements and population aging.


Immunocytochemical localization of metabotropic (mGluR2/3 and mGluR4a) and ionotropic (GluR2/3) glutamate receptors in adrenal medullary ganglion cells.
The localization of metabotropic glutamate receptors of groups II (mGluR2/3) and III (mGluR4a) and the subunits 2 and 3 of alfa-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) ionotropic glutamate receptors (GluR2/3) was investigated with immunocytochemical methods in the rat adrenal gland. MGluR2/3, mGluR4a and GluR2/3 immunoreactivities were observed in large-sized, centrally located type I adrenal medullary ganglion neurons. Furthermore, the small-sized type II adrenal ganglion neurons identified by their immunoreactivity to brain nitric oxide synthase (bNOS), also expressed mGluR2/3, mGluR4a and GluR2/3. These cells were disposed in the peripheral portion of the adrenal medulla. None of the type I neurons were positively labeled for bNOS. These morphological observations suggest that activation of glutamate receptors in ganglion neurons may be instrumental in the control of adrenal endocrine systems as well as blood regulation.


A pilot study. Depth perception and near stereoacuity: is it related to academic performance in young children?
A study of the relationship between an overall measure of visual function at near, specifically stereoacuity, and academic performance in kindergarten through second grade was conducted. One hundred seventeen children (mean age = 7.33 +/-0.97 years) from a middle class, suburban, elementary school participated in this masked investigation. The Randot 2 stereotest was used to measure stereoacuity at 40 cm. The relationship between stereoacuity and teachers' personal ratings of academic ability was analyzed because teachers' grades are a primary means of assessing school performance. The children's regular classroom teachers rated the children with respect to reading, mathematics, and writing ability. Children in the second grade (n = 47) were also rated on spelling ability. Only experienced teachers were included in the investigation and the validity of the teachers' rating was substantiated by significant correlations with standardized test scores. Teachers were masked to performance on the stereotest. Performance on the Randot was found to be "statistically significantly" (p=<0.05) and "medically-clinically significantly" related to standardized reading test scores (p=0.033) and teachers' personal ratings of reading (p<0.001), mathematics (p<0.001), writing (p<0.001) and spelling (p=0.048) ability. Good visual function at near, particularly good stereoacuity, is significantly correlated to academic performance.


Double gaps along Shaker S4 demonstrate omega currents at three different closed states.
The aim of the present study was to investigate in detail how the voltage sensor in the Shaker potassium channel moves during the gating process. After the publication of the open channel structure from the crystallized K(V)AP channel in 2003, an alternative so-called "paddle" model was put forward in contrast to the existing helical screw model. The voltage sensor S4 contains 4 arginine residues relevant for gating, R1(362), R2(365), R3(368) and R4(371), each separated by 2 neutral residues. These charged residues coil as one of three threads on the S4-alpha-helix. Based on a previous finding that the mutation R1S leads to the so-called omega leak current through a "gating-pore" in the closed state, we introduced gaps systematically along the arginine thread substituting long arginines by short serines. Mutations R2S or R3S did neither create transient nor steady leaks. The fact that the native residue A359, which is located three amino acids in front of R1, is a short one, motivated us to check its role. Mutation of A359 to arginine blocked the omega current in the R1S mutant indicating that the omega pore is occupied by A359 and R1. Introducing further double gaps (RR to SS) at sequential positions (0 + 1, 1 + 2, 2 + 3), produced clear leak currents which were remarkably stable over a wide voltage range. These leaks contradict that S4 would swing together with S3 in lipid according to the paddle hypothesis. Rather, our results show that during gating the S4 segment moves in 3 helical steps through a fixed pore formed by the channel protein.


[Epididymal sperm protein P34H and male reproduction].
During epididymal transit, mammalian spermatozoa acquire new surface proteins that are necessary for gamete interaction. P34H, a member of the short-chain dehydrogenase/reductase(SDR) superfamily, is acquired on the acrosomal cap of human spermatozoon during its maturation arising within epididymis. P34H has been shown to be involved in sperm-zona pellucida interaction. Research revealed that the occurrence of low concentration of sperm protein P34H were significant amongst the idiopathic infertile male population and P34H protein could also be considered as a marker of epididymal sperm maturation in human. Therefore the level of sperm protein P34H is proposed to be a auxiliary diagnostic tool for male infertility. This paper reviews the molecular properties and regulation of the expression of P34H and its association with male reproduction.


Waterpipe smoking: the pressing need for risk communication.
Introduction: Waterpipe (WP) smoking is an important public health problem that is rapidly evolving globally. Much of WP spread among youth is perpetuated by a misperception of reduced harms compared to cigarettes. Increasing awareness about WP smoking harms through health warning labels (HWLs) represents a promising policy and regulatory strategy to curb WP smoking. Areas covered: Peer-reviewed publications indexed in PubMed and CINAHL were searched in March 2019. This review focuses on the current knowledge of WP smoking characteristics, its spread and patterns of use globally, and some of the major WP-related health effects. This knowledge is utilized to advance a promising policy and regulatory avenue to curb WP smoking by increasing awareness of its potential harms through HWLs. It also addresses product configuration and unique features that influence the adaptation of HWLs for WP smoking. Expert opinion: HWLs are effective in communicating smoking-related risks to WP smokers in a way that affects their smoking behavior and experience as well as interest in quitting. Although based on limited data, the WP device appears to be a promising location for HWLs as it offers prolonged contact with smokers and those surrounding them.


The pioneer round of translation ensures proper targeting of ER and mitochondrial proteins.
The pioneer (or first) round of translation of newly synthesized mRNAs is largely mediated by a nuclear cap-binding complex (CBC). In a transcriptome-wide analysis of polysome-associated and CBC-bound transcripts, we identify RN7SL1, a noncoding RNA component of a signal recognition particle (SRP), as an interaction partner of the CBC. The direct CBC-SRP interaction safeguards against abnormal expression of polypeptides from a ribosome-nascent chain complex (RNC)-SRP complex until the latter is properly delivered to the endoplasmic reticulum. Failure of this surveillance causes abnormal expression of misfolded proteins at inappropriate intracellular locations, leading to a cytosolic stress response. This surveillance pathway also blocks protein synthesis through RNC-SRP misassembled on an mRNA encoding a mitochondrial protein. Thus, our results reveal a surveillance pathway in which pioneer translation ensures proper targeting of endoplasmic reticulum and mitochondrial proteins.


Cholesterol oxidase from Rhodococcus erythropolis with high specificity toward β-cholestanol and pytosterols.
Two genes (choRI and choRII) encoding cholesterol oxidases belonging to the vanillyl-alcohol oxidase (VAO) family were cloned on the basis of putative cholesterol oxidase gene sequences in the genome sequence data of Rhodococcus erythropolis PR4. The genes corresponding to the mature enzymes were cloned in a pET vector and expressed in Escherichia coli. The two cholesterol oxidases produced from the recombinant E. coli were purified to examine their properties. The amino acid sequence of ChoRI showed significant similarity (57%) to that of ChoRII. ChoRII was more stable than ChoRI in terms of pH and thermal stability. The substrate specificities of these enzymes differed distinctively from one another. Interestingly, the activities of ChoRII toward β-cholestanol, β-sitosterol, and stigmasterol were 2.4-, 2.1-, and 1.7-fold higher, respectively, than those of cholesterol. No cholesterol oxidases with high activity toward these sterols have been reported so far. The cholesterol oxidation products from these two enzymes also differed. ChoRI and ChoRII oxidized cholesterol to form cholest-4-en-3-one and 6β-hydroperoxycholest-4-en-3-one, respectively.


Purinergic P2X receptors: structural and functional features depicted by X-ray and molecular modelling studies.
The publication of the first crystal structures of the zebrafish P2X4 receptor in 2009 was a pivotal moment; for the first time, researchers were able to interpret their experimental data in a structural context. Several research groups immediately set about using the data to make molecular models of the better-understood mammalian P2X receptors, in order to design and interpret the results of new, more focused structure-function experiments. In 2012, the publication of the crystal structure of zebrafish P2X4 in the ATP-bound state gave further insights into the mechanism of ligand binding and its coupling to ion channel activation, initiating a new cycle of modelling, experimentation and interpretation. The purpose of this review is to describe our current understanding of the 3D-structure of P2X receptors, by highlighting the strengths and limitations of the zebrafish P2X4 crystal structures, discussing how the molecular models derived from them have been made, and what they have been used for, and explaining why crystal structures of mammalian P2X receptors are still needed to uncover the molecular mechanisms of differential agonist/antagonist potency, allosteric modulation, pore dilatation and desensitisation.


Control of Light Transmission in a Plasmonic Liquid Metacrystal.
In this study, we experimentally demonstrated the control of light transmission through a slab of plasmonic liquid metacrystal by an external electric field. By applying the external static field, we were able to induce macroscopic anisotropy, which caused the polarization-dependent suppression of transmission at resonant frequencies. Such behavior indicates the selective plasmon excitation governed by the orientation of the meta-atoms with respect to the polarization of the electromagnetic wave. The problem of light transmission through a plasmonic liquid metacrystal was analyzed theoretically from first principles, and the obtained results were compared with the experimental data.


Relationship Between Pain Management Modality and Return Rates for Lower Back Pain in the Emergency Department.
Emerging evidence suggests that opioid use for patients with acute low back pain does not improve functional outcomes and contributes to long-term opioid use. Little is known about the impact of opioid administration in the emergency department (ED) for patients with low back pain. This study compares 30-day return rates after administration of various pain management modalities for emergency department (ED) patients with low back pain. We conducted a retrospective multicenter observational study of patients in the ED who were diagnosed with low back pain and discharged home in 21 EDs between November 2018 and April 2020. Patients were categorized based on the pain management they received in the ED and compared with the reference group of patients receiving only nonsteroidal anti-inflammatory drugs, acetaminophen, or a combination of the two. The proportions of ED return visits within 30 d for each medication category was calculated and associations between analgesia categories and proportions of return visits were assessed using logistic regression models to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Patients with low back pain who received any opioid, intravenous opioid, or intramuscular opioid had significantly increased proportions of a return visit within 30 d (32% [OR 1.78 {95% CI 1.21-2.64}]; 33% [OR 1.83 {95% CI 1.18-2.86}]; and 39% [OR 2.38 {95% CI 1.35-4.12}], respectively) when compared with patients who received nonsteroidal anti-inflammatory drugs (19%), acetaminophen (20%), or a combination of the two (8%). Patients receiving opioids were more likely to return to the ED within 30 d than those receiving received nonsteroidal anti-inflammatory drugs or acetaminophen. This suggests that the use of opioids for low back pain in the ED may not be an effective strategy, and there may be an opportunity to appropriately treat more of these patients with nonopioid medications.


The fasciovascular pedicle for revascularization of other tissues.
A fasciovascular pedicle based on the epigastric vessels was developed in a rat model to determine if it could be used as a "universal carrier" to revascularize a new composite flap. The effects of time course, carrier size, and flap ischemia on the revascularization process were studied. A 2.5 x 4-cm or 1 x 4-cm fascial patch pedicled on the vessels was transferred under bipedicled 2.5 x 4-, 6-, or 8-cm abdominal panniculocutaneous flaps. At different time intervals, the flap was raised as an island flap connected only by it vascular bundle and then sutured back in place. The skin perfusion by dermofluorometry and flap survival were both markedly increased on day 5 (p less than 0.001). The wide carrier had a 93% survival area, whereas the narrow carrier had only 71%. The wide carrier induced relatively faster and better revascularization (p less than 0.05). Moderate ischemia promoted revascularization (p less than 0.01). An india ink injection study and histological examination provided visual evidence of revascularization. This fasciovascular pedicle is a promising model for prefabrication of complex new composite flaps and for studying the process of revascularization between the layers. Based on these findings and further investigations, a thin, prefabricated abdominal free flap was successfully transferred for facial resurfacing in humans.


Angiotensin II induction of neurite outgrowth by AT2 receptors in NG108-15 cells. Effect counteracted by the AT1 receptors.
In the present study, 3-day treatment of nondifferentiated NG108-15 cells with 100 nM angiotensin II (Ang II) induces morphological differentiation of neuronal cells characterized by the outgrowth of neurites. These morphological changes are correlated with an increase in the level of polymerized tubulin and in the level of the microtubule-associated protein, MAP2c. Mediation by the AT2 receptor may be inferred since: (a) these cells contain only AT2 receptors; (b) the effects are mimicked by CGP 42112 (an AT2 receptor agonist); (c) they are not suppressed by the addition of DUP 753 (an AT1 receptor antagonist); and (d) are abolished by co-incubation with PD 123319 (an AT2 receptor antagonist). Application of Ang II in dibutyryl cAMP-differentiated cells (which contain both types of receptors) induces neurite retraction, an effect mediated by the AT1 receptor. These results indicate that the AT2 receptor of Ang II induces neuronal differentiation, which is initiated through an increase in the levels of MAP2c associated with tubulin. Moreover, our results demonstrate that the AT1 receptor inhibit the process of differentiation induced by dibutyryl cAMP, whereas the AT2 receptors potentiate this effect, illustrating negative cross-talk interaction between the two types of Ang II receptors.


A novel Candida glabrata doxycycline-inducible system for in vitro/in vivo use.
Candida glabrata is an important pathogen causing superficial to invasive disease in human. Conditional expression systems are helpful in addressing the function of genes and especially when they can be applied to in vivo studies. Tetracycline-dependent regulation systems have been used in diverse fungi to turn-on (Tet-on) or turn-off (Tet-off) gene expression either in vitro but also in vivo in animal models. Up to now, only a Tet-off expression has been constructed for gene expression in C. glabrata. Here, we report a Tet-on gene expression system which can be used in vitro and in vivo in any C. glabrata genetic background. This system was used in a mice model of systemic infection to demonstrate that the general amino acid permease Gap1 is important for C. glabrata virulence.


Low level determination of 4-amino-2-ethoxy-cinnamic acid and its ethyl ester in a drug substance and its formulation prototypes by HPLC-UV-DAD.
A reversed-phase high-performance liquid chromatographic method (HPLC) with diode-array detection (DAD) has been evaluated for monitoring trace levels of impurities, such as 4-amino-2-ethoxy-cinnamic acid (impurity A), hydrochloride salt of 4-amino-2-ethoxy-ethyl cinnamate (impurity B), and 4-bromo-3-ethoxy-nitrobenzene (impurity C), in drug substance and 3 different formulation prototypes. These compounds have been highlighted as potential genotoxins and 2-ethoxy-4-amino-cinnamic acid (impurity A) as possible degradant isolated during the synthesis of BI drug substance. HPLC-UV-DAD was found to be more promising, and limits of quantification were between 0.09 and 0.6 microg/mL, which enabled detection limits in drug substance at 2-15 ppm for a 15 mg/mL solution. All three genotoxic impurities are completely resolved from each other as well as from diluent peaks, drug substance, and other related impurities within 40 min. The retention times of impurities A, B, and C were 3.4, 13.1, and 21.3 min. The results demonstrating the specificity, assay precision, recovery, linearity, and range achieved during the method validation experiments are presented in this paper.


Infective endocarditis complicated with rapidly progressive glomerulonephritis: a case report.
A 26-year-old man who had suffered from intermittent chills and fever over a two month period was quite clear of heart or kidney involved developed acute deterioration of renal function. A new pansystolic murmur over the apex of the heart was heard on auscultation, and echocardiography clearly showed a vegetation about 0.7-0.9 cm in size on the atrial site of the mitral value. Laboratory investigation displayed normochromic anemia with negative Coombs' test. Immunological studies were positive for rheumatoid factor and circulating immune complex. High serum levels of erythrocyte sedimentation rate and C-reactive protein, nephritic sediment of urinalysis and negative blood cultures for bacteria, tuberculosis or fungus were also noted. Abdominal sonography showed normal kidney size, bilaterally. Renal biopsy revealed typical crescentic glomerulonephritis. After intravenous penicillin therapy for two weeks, the serum creatinine level recovered from 6.7 mg/dl to 2.0 mg/dl and circulating immune complex disappeared. In consideration of cardiac insufficiency and the potential risk for complications of the vegetation, the patient underwent mitral valve replacement. Four weeks after operation, all the abnormal data had resolved completely. These data suggested that infective endocarditis with rapidly progressive glomerulonephritis is curable by antibiotic therapy and surgical intervention.


A novel cAMP-stimulated pathway in protein phosphatase 2A activation.
Elevated cAMP in NRK-52E and L6 cells causes a marked reduction in the phosphorylation of numerous phosphoproteins, as detected initially with phosphoserine-specific antibodies. Here, we show that elevation of cAMP in NRK cells by forskolin/3-isobutyl-1-methylxanthine (IBMX) treatment decreased phosphorylation of substrates for different protein kinases, pointing to a common protein phosphatase as a target for cAMP-dependent regulation. Forskolin/IBMX treatment completely dephosphorylated a selective protein phosphatase 2A (PP2A) substrate, elongation factor-2 (EF-2), at its Ca(2+) calmodulin-dependent kinase site, and decreased phosphorylation of substrates for cyclin-dependent kinases, including retinoblastoma (Rb) protein. As reported before, forskolin/IBMX also decreased phosphorylation of a protein kinase C substrate, the Na,K-ATPase. The cAMP-stimulated dephosphorylation was blocked by the protein phosphatases 1 (PP1) and PP2A inhibitor okadaic acid at concentrations selective for PP2A but was not blocked by tautomycin at concentrations selective for PP1. The data implicate PP2A as a cAMP-activated phosphatase. Contrary to expectation, we found evidence that cAMP-dependent activation of PP2A did not depend on protein kinase A (PKA). Pretreatment of cells with the PKA inhibitor H89 abolished PKA activity measured in cell extracts and significantly decreased cAMP-activated phosphorylation of a known PKA substrate, ARPP-19, in cells, but failed to block the cAMP-stimulated dephosphorylation of EF-2, Rb, and other proteins. This novel pathway of PP2A activation, acting on the time scale of minutes, represents yet another example of a cAMP-mediated, PKA-independent signaling mechanism. Because PP2A is active toward a variety of endogenous substrates, cAMP-stimulated dephosphorylation may have complicated the interpretation of many prior studies.


Atorvastatin protects cardiac progenitor cells from hypoxia-induced cell growth inhibition via MEG3/miR-22/HMGB1 pathway.
Heart failure (HF) induced by ischemia myocardial infarction (MI) is one of the major causes of morbidity and mortality all around the world. Atorvastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, has been demonstrated to benefit patients with ischemic or non-ischemic-induced HF, but the mechanism is still poorly understood. Increasing evidence indicates that lncRNAs play important role in variety of human disease. However, the role and underlying molecular mechanisms remain largely unclear. In our work, we applied 0.5% O2 to generate a hypoxia cardiac progenitor cell (CPC) model. Then, CCK8 and EdU assays were employed to investigate the role of atorvastatin in hypoxia CPC cell model. We found that hypoxia inhibits CPC viability and proliferation through modulating MEG3 expression, while atorvastatin application can protect CPCs from hypoxia-induced injury through inhibiting MEG3 expression. Then, we demonstrated that repression of MEG3 inhibited the hypoxia-induced injury of CPCs and overexpression of MEG3 inhibited the protective effect of atorvastatin in the hypoxia-induced injury of CPCs. Furthermore, our study illustrated that atorvastatin played its role in CPC viability and proliferation by modulating the expression of HMGB1 through the MEG3/miR-22 pathway. Our study, for the first time, uncovered the molecular mechanism of atorvastatin's protective role in cardiomyocytes under hypoxia condition, which may provide an exploitable target in developing effective therapy drugs for MI patients.


Characterization and differentiation of ruthenium(II) complexes with 1,4,7-trithiacyclononane and nitrogen heterocycles by electrospray mass spectrometry.
Electrospray ionization mass spectrometry (ESIMS) was used to characterize a series of new ruthenium(II) complexes with several nitrogen heterocycles and a common ligand: the crown thioether 1,4,7-trithiacyclononane, [9]aneS(3). ESIMS allows the easy identification of the [Ru(II)Cl([9]aneS(3))Y]X complexes, where Y is a bidentate nitrogen heterocycle and X is Cl(-) or PF(6)(-), through the formation of two diagnostic ions by fragmentation of the common ligand [9]aneS(3). Structures for these ions and mechanisms for their gas-phase formation are proposed based on data from product ion spectra.


[Protective effect and mechanism of scutellarin ethyl ester on focal cerebral ischemia induced by ligation of middle cerebral artery in rats].
To observe the protective effect of scutellarin ethyl ester on focal cerebral ischemia injury induced by middle cerebral artery occlusion in rats(MCAOR), and explore its mechanism. Totally 84 male SD rats were randomly divided into seven groups: sham-operated group, model group,positive drug group(niomdipine,12 mg•kg⁻¹), Brevisapin tablets group(48 mg•kg⁻¹), and high, middle and low-dose scutellarin ethyl ester groups(100, 50, 25 mg•kg⁻¹). The MCAOR model was prepared by using thread embolism method to observe the neurological function of rats, the area of cerebral infarction was measured with TTC, and the levels of MDA, SOD and NO in serum were detected with semiautomatic biochemistry analyzer.Ox-LDL and TNF-α cell injury models was established by treating HUVECs with 200 mg•L⁻¹ ox-LDL and 100 μg•L⁻¹ TNF-α,and the levels of MDA, SOD, NO, ET, 6-keto-PGF1α,TXB2, IL-1, IL-6, IL-8, ICAM-1 and PECAM-1 in the cell supernatant were determined. The results showed that scutellarin ethyl ester could effectively improve the neurological function of MCAOR rats, and significantly reduce the area of cerebral infarction. Compared with the model group, activities of SOD and NO in serum increased, while content of MDA decreased. In the cell supernatant, activities of SOD, 6-keto-PGF1α and NO increased, content of IL-1, IL-6, IL-8, ICAM-1, PECAM-1, TXB2, ET and MDA decreased, which indicated that scutellarin ethyl ester has a certain protective effect on focal cerebral ischemia injury induced by middle cerebral artery occlusion in rats, and its mechanism may be related to antioxidative stress, improvement of endothelial function and reduction in inflammatory reaction.


A case study in integrative medicine: alternative theories and the language of biomedicine.
In this case study, a diverse panel of 6 practitioners of mainstream and/or alternative medicine plus a moderator convened as an experiment in practicing integrative medicine to examine, diagnose, and prescribe for a patient suffering from chronic, severe, treatment-resistant back pain. Although panel members represented a wide range of theories of health and healing, they were able to communicate easily with one another by limiting themselves to the scientific language of biomedicine. From the perspective of medical anthropology, this can be interpreted as an unplanned and unconscious process of cultural imitation in a medical marketplace in which cultural differentiation formerly prevailed. Although the shift from differentiation to imitation was limited in this experiment to the sharing of a single language of discourse and to recommendations of mutually compatible treatment options, it raises an important question. With the institutionalization of integrated medical practice, will alternative medical systems survive only if they are stripped down to being no more than alternative therapeutic modalities?


Tumoricidal activity of interferon-r activated peripheral monocytes in colorectal cancer patients.
Peripheral blood monocytes obtained from 8 colorectal cancer patients and 6 normal controls were incubated in vitro with interferon-r (IFN-r) in the presence of bacterial lipopolysaccharide (LPS). The cytotoxic properties of the monocyte were determined subsequent to the interaction with radiolabeled autologous, allogeneic, as well as cultured colorectal cancer cells. Monocytes from normal controls and all colorectal cancer patients were activated in vitro to become tumoricidal; monocytes lysed tumorigenic cells but not nontumorigenic cells. Activators of protein kinase C (e.g. phorbol esters, PMA) and Ca2+ ionophores (A23187) when added alone did not effect the activation state of the monocyte. Whereas, PMA and A23187 cooperatively reproduced the ability of IFN-r to prime monocytes for tumoricidal activity. In the presence of PMA, A23187, and EGTA, the addition of excessive Ca2+ was sufficient for priming, whereas the addition of excessive Mg2+ was much less efficient. Priming by IFN-r, however, was not blocked by EGTA. An efflux of Ca2+ from preloaded monocytes was significantly increased by A23187 and by IFN-r. Quin-2/AM, an intracellular chelator of Ca2+, blocked priming by IFN-r. The results suggest that priming of monocytes for tumoricidal function by IFN-r may be involved in the activation of protein kinase C and mobilization of intracellular Ca2+.


Development and in-vitro evaluation of sustained release poloxamer 407 (P407) gel formulations of ceftiofur.
The objective of this study was to develop sustained release Poloxamer 407 (P407) gel formulations of ceftiofur for treating foot infections in cattle. The formulations contained 25-35% (w/v) P407 alone or with polyvinyl pyrrolidone (PVP), carboxy methylcellulose (CMC), or hydroxylpropyl methylcellulose (HPMC) as an additive. The in-vitro release profiles of ceftiofur from the P407 formulations and the gel dissolution profiles were obtained simultaneously. Ceftiofur release followed zero order kinetics and correlated well with the weight percentage of P407 dissolved, indicating that the overall rate of release of ceftiofur is controlled by dissolution of the P407. An increase in P407 content from 25 to 35% resulted in a decrease in the rate of ceftiofur release. However, it appears that other factors may have also affected the drug release rate. Inclusion of PVP, CMC, and HPMC in the gel decreased the rate of release of ceftiofur to some extent. A decrease in the temperatures of the release medium decreased the release rate of ceftiofur, but not the rate of gel dissolution. The pH of the release medium showed a very slight effect on the release of ceftiofur and did not affect gel dissolution due to the non-ionic nature of P407.


NAD+ metabolism and NAD(+)-dependent enzymes: promising therapeutic targets for neurological diseases.
Numerous studies have indicated that four interacting factors, including oxidative stress, mitochondrial alterations, calcium dyshomeostasis and inflammation, play crucial pathological roles in multiple major neurological diseases, including stroke, Alzheimer's disease (AD) and Parkinson's disease (PD). Increasing evidence has also indicated that NAD(+) plays important roles in not only mitochondrial functions and energy metabolism, but also calcium homeostasis and inflammation. The key NAD(+)-consuming enzyme--poly(ADP-ribose) polymerase-1 (PARP-1) and sirtuins--have also been shown to play important roles in cell death and aging, which are two key factors in the pathology of multiple major age-dependent neurological diseases: PARP-1 plays critical roles in both inflammation and oxidative stress-induced cell death; and sirtuins also mediate the process of aging, cell death and inflammation. Thus, it is conceivable that increasing evidence has suggested that NAD(+) metabolism and NAD(+)-dependent enzymes are promising targets for treating a number of neurological illnesses. For examples, the key NAD(+)-dependent enzymes SIRT1 and SIRT2 have been indicated to strongly affect the pathological changes of PD and AD; PARP-1 inhibition can profoundly reduce the brain injury in the animal models of multiple neurological diseases; and administration of either NAD(+) or nicotinamide can also decrease ischemic brain damage. Future studies are necessary to further investigate the roles of NAD+ metabolism and NAD⁺-dependent enzymes in neurological diseases, which may expose novel targets for treating the debilitating illnesses.


Long-range resonance energy transfer in molecular systems.
The current state of understanding of molecular resonance energy transfer (RET) and recent developments in the field are reviewed. The development of more general theoretical approaches has uncovered some new principles underlying RET processes. This review brings many of these important new concepts together into a generalization of Förster's original theory. The conclusions of studies investigating the various approximations in Förster theory are summarized. Areas of present and future activity are discussed. The review covers Förster theory for donor-acceptor pairs and electronic coupling for singlet-singlet, triplet-triplet, and superexchange-mediated energy transfer. This includes the transition density picture of Coulombic coupling as well as electronic coupling between molecular aggregates (excitons). Spectral overlaps and ensemble energy transfer rates in disordered aggregates, the role of dielectric properties of the medium, weak versus strong coupling, and new models for energy transfer in complex molecular assemblies are also described.


Antinociceptive and adverse effects of mu- and kappa-opioid receptor agonists: a comparison of morphine and U50488-H.
Although mu-opioids such as morphine are undoubtedly effective in the treatment of acute and postoperative pain, kappa-opioids are of interest for the modulation of visceral pain. In the present study, we compared a kappa-opioid agonist (U50488-H; 0.63-40 mg/kg) with a mu-opioid agonist (morphine; 0.63-40 mg/kg) in different pain models (tail withdrawal, writhing, formalin and plantar test) to represent acute, peritoneovisceral and inflammatory pain states in rats. The effects of the respective receptor agonists on gastrointestinal motility, muscle rigidity and abuse liability were also studied in appropriate animal models (charcoal, castor oil, rotarod and drug discrimination learning). Morphine was highly efficacious in all the nociceptive models employed, but also elicited a potent inhibition of gastric motility, caused severe muscle rigidity and locomotor disturbances and displayed a potential for abuse liability at the higher doses tested (> or =10 mg/kg morphine). In contrast, U50488-H was inactive in the tail withdrawal test, but was more effective in visceral and inflammatory pain settings. Although U50488-H did not elicit any gastrointestinal inhibition, a loss of muscle tone following administration of the compound led to detrimental effects on rotarod performance. The findings presented here indicate that kappa-opioids possess antinociceptive efficacy in visceral and inflammatory pain settings, but their administration can lead to a loss of muscle tone. In contrast, mu-opioids are highly active as analgesics against a range of nociceptive stimuli, but also concomitantly elicit strongly adverse effects.


Deconstructing the "reign of error": interpersonal warmth explains the self-fulfilling prophecy of anticipated acceptance.
People's expectations of acceptance often come to create the acceptance or rejection they anticipate. The authors tested the hypothesis that interpersonal warmth is the behavioral key to this acceptance prophecy: If people expect acceptance, they will behave warmly, which in turn will lead other people to accept them; if they expect rejection, they will behave coldly, which will lead to less acceptance. A correlational study and an experiment supported this model. Study 1 confirmed that participants' warm and friendly behavior was a robust mediator of the acceptance prophecy compared to four plausible alternative explanations. Study 2 demonstrated that situational cues that reduced the risk of rejection also increased socially pessimistic participants' warmth and thus improved their social outcomes.


[Intra-abdominal hypertension and multiple organ dysfunction syndrome].
In clinical practice, intra-abdominal pressure is usually measured indirectly via the urinary bladder using Foley catheter. This technique is minimally invasive, safe, simple and accurate. Intra-abdominal hypertension is defined as an intra-abdominal pressure above 12 mmHg. Rapid progression of intra-abdominal hypertension will lead to abdominal compartment syndrome, which is defined as an intra-abdominal pressure greater than 20 mmHg with at least one organ failure. The incidence of intra-abdominal hypertension is variable and depends on the values used to define it and on the study population. However, the mortality rate of intra-abdominal hypertension and abdominal compartment syndrome is high. Increase in intra-abdominal pressure causes significant impairment of almost all organ systems. Even slight increase in intra-abdominal pressure has negative influence on the respiratory, cardiovascular, cerebral, gastrointestinal, hepatic, and renal functions. Intra-abdominal hypertension causes visceral organ hypoperfusion, intestinal ischemia and may also lead to bacterial translocation, release of cytokines and production of free oxygen radicals. All these factors may contribute to the development of multiple organ failure in the critically ill patients. Intravascular fluid replacement and abdominal decompression are the standards of treatment for abdominal compartment syndrome.


Heterogeneity of BRAF, NRAS, and TERT Promoter Mutational Status in Multiple Melanomas and Association with MC1R Genotype: Findings from Molecular and Immunohistochemical Analysis.
Data on somatic heterogeneity and germline-somatic interaction in multiple primary melanoma (MPM) patients are limited. We investigated the mutational status of BRAF, NRAS, and TERT promoter genes in 97 melanomas of 44 MPM patients and compared molecular and immunohistochemical findings. We further evaluated the association of somatic alterations with the germline MC1R genotype. Mutations in BRAF gene were identified in 41.2% (40/97) of melanomas, in NRAS in 2.1% (2/97), and in TERT promoter in 19.6% (19/97). Distribution of BRAF mutations did not differ across multiple melanomas (P = 0.85), whereas TERT promoter changes decreased from first to subsequent melanomas (P = 0.04). Intrapatient discrepancy of BRAF mutations among multiple tumors was detected in 14 of 44 MPM patients (32%) and of BRAF/NRAS/TERT promoter genes in 20 of 44 (45%). We observed a high rate of agreement between allele-specific TaqMan assay and immunohistochemistry in BRAFV600E detection (κ = 0.83, P < 0.01) with 86 of 97 melanomas (88.7%) presenting similar BRAF status. Germline MC1R variants were identified in 81.4% (35/43) of MPM patients with no association of MC1R genotype with somatic mutations or with intrapatient concordance of somatic mutational profile. Our results support the genetic diversity of multiple melanomas and show that somatic heterogeneity is not influenced by inherited MC1R variants. Immunohistochemistry may be useful as an initial screening test.


The vermilion-sharing graft for repairing a vermilionectomy defect.
Lower lip vermilionectomy defects can be repaired with a full-thickness graft of vermilion from the upper lip. The graft width should be approximately one-half that of the lower lip defect, sharing the vermilion between the two lips. The graft should be oriented so that the red, anterior part of the vermilion is placed anteriorly, where it will be most visible. If graft "take" is successful, the result can be aesthetically and functionally excellent, while the donor-site morbidity is minimal.


Demonstration of specific binding of cocaine to human spermatozoa.
Exposure of males to cocaine has been linked to abnormal development of their offspring. To investigate the possible role of sperm, this study examined the interaction of cocaine with human spermatozoa. Washed sperm were incubated with tritiated cocaine (6.7 nmol/L) with or without unlabeled cocaine (670 mumol/L), and the samples were filtered and the remaining radioactivity quantitated. The specific binding was optimal at 20 minutes and 23 degrees C. Competition studies with tritiated cocaine (3.4 to 66.6 nmol/L) indicated the presence of approximately 3.6 x 10(3) binding sites per cell, with a high affinity receptor dissociation constant (Kd = 12.6 nmol/L). Cocaine concentrations as high as 670 mumol/L had no detectable effect on either the motility or viability of the cells. These results support the hypothesis that the sperm may act as a vector to transport cocaine into an ovum. This novel mechanism could be involved in the abnormal development of offspring of cocaine-exposed males.


[Chinese burn referral criteria (2018 version)].
There is no national referral criteria for burns in China till now, which brings inconvenience and confusion. Based on the oversea experiences and the actual situation in China, many famous experts in burns discussed and developed this Chinese burn referral criteria (2018 version). We hope these referral criteria will be helpful in clinical practice of burns and can be improved continuously through application.


[Midwives' feelings about the post-partum care of women with severe mental illness: A qualitative analysis].
A significant proportion of women with Severe Mental Illness (SMI) will become mothers during their reproductive life. These pregnancies are, however, more at risk of psychiatric, obstetrical and neonatal complications (increased risks of post-partum depression, relapse, suicide, gestational diabetes, placental abnormalities or low birth weight). Midwives often feel isolated and resourceless when taking care of these women. Specialized units such as mother-infant psychiatric units or the Transversal Unit of Perinatal Care (UTAP) in the Grenoble Alpes University Hospital (CHUGA) enhance the coordination between psychiatric and obstetrical teams and have shown effectiveness in improving maternal and child outcomes. i) to assess midwives' feelings about the postpartum care of women with SMI; ii) to determine UTAP's impact on this feeling and its determinants; iii) to look for unmet needs. This study is a prospective, exploratory, qualitative analysis. Twenty midwives from Grenoble Alpes University Hospital who took care of one of the selected patients participated in this study. Two women had schizophrenia and one bipolar disorder. Interviews realized with a semi-structured guide were fully transcribed, anonymized and thematically analyzed. Topics have been structured according to the number of occurrences to build a thematic tree. Midwives felt insecure and resourceless when the postpartum care was unclear, insufficiently anticipated and in case of a danger for the women or the children. They felt uneasy when not feeling able to provide usual care to these patients (due to lack of specific knowledge about SMI and to the impossibility to consider their patient otherwise than through their pathology). Midwives felt at ease and secure when the postpartum care was anticipated. UTAP was identified as a resource for midwives. Specific training and improvements in the organization of the pre and post-natal care could improve midwives' feelings when taking care of women with SMI.


Water, sanitation and hygiene in developing countries: interventions and diarrhoea--a review.
We conducted a search to identify all English language papers (published between 1 January 1985 and 26 June 2003) with evidence on the effectiveness of water, sanitation and hygiene interventions in developing countries, in which diarrhoea morbidity in non-outbreak conditions was reported. A total of 39 studies were identified as relevant after an initial review of over 2000 titles. Data were extracted and, where possible, combined using meta-analysis to provide a summary estimate of the effectiveness of specific interventions, including water supply and water treatment. Most of the interventions (including multiple interventions, hygiene and water quality) were found to significantly reduce the levels of diarrhoeal illness, with the greatest impact being seen for hygiene and household treatment interventions (after removal of studies classed as poor quality). Sanitation interventions could not be assessed as only a single study suitable for meta-analysis was identified.


Additives Imparting Antimicrobial Properties to Acrylic Bone Cements.
PMMA bone cements are mainly used to fix implanted prostheses and are introduced as a fluid mixture, which hardens over time. The problem of infected prosthesis could be solved due to the development of some new antibacterial bone cements. In this paper, we show the results obtained to develop four different modified PMMA bone cements by using antimicrobial additives, such as gentamicin, peppermint oil incorporated in hydroxyapatite, and silver nanoparticles incorporated in a ceramic glass matrix (2 and 4%). The structure and morphology of the modified bone cements were investigated by SEM and EDS. We perform experimental measurements on wettability, hydration degree, and degradation degree after immersion in simulated body fluid. The cytotoxicity was evaluated by MTT assay using the human MG-63 cell line. Antimicrobial properties were checked against standard strains Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The addition of antimicrobial agents did not significantly affect the hydration and degradation degree. In terms of biocompatibility assessed by the MTT test, all experimental PMMA bone cements are biocompatible. The performance of bone cements with peppermint essential oil and silver nanoparticles against these two pathogens suggests that these antibacterial additives look promising to be used in clinical practice against bacterial infection.


HIF-1alpha is an unfavorable determinant of relapse in gastric cancer patients who underwent curative surgery followed by adjuvant 5-FU chemotherapy.
Among several chemotherapeutic agents, 5-fluorouracil (5-FU) has been widely used as a key drug in adjuvant chemotherapy for gastric cancer. However, no reliable marker, which predicts the response to 5-FU in an adjuvant setting, has been identified. Hypoxia-induced drug resistance, via upregulation of HIF-1alpha, is a major obstacle in the development of effective cancer therapy. However, few clinical studies have so far assessed the relationship between the HIF-1alpha expression and the chemo-resistance of gastric cancer patients in an adjuvant setting. We established 2 HIF-1alpha knockdown gastric cancer cell lines in order to clarify the role of HIF-1alpha in chemo-resistance against 5-FU. Furthermore, expression of HIF-1alpha was immunohistochemically assessed in 91 resected specimens. Sixty-four of 91 patients received 5-FU adjuvant chemotherapy after surgery. HIF-1alpha expression was associated with the significantly shorter relapse-free survival and disease-specific survival in the 64 patients of adjuvant group (p = 0.026, 0.014, respectively), but not in the 27 of surgery group. Multivariate analysis showed that HIF-1alpha was an independent risk factor for relapse in 64 patients in the adjuvant group (p = 0.029). In conclusion, the current study confirmed, for the first time that HIF-1alpha expression is an independent risk factor for relapse in high-risk gastric cancer patients who underwent curative surgery followed by adjuvant 5-FU chemotherapy. A favorable effect of 5-FU might therefore be expected in patients that do not express HIF-1alpha, whereas, other types of chemotherapy or additional treatments, such as HIF-1alpha inhibitors, should be considered in patients that do express HIF-1alpha.


Carcinoma of the prostate. Serum tumour markers.
Health examination - screening: Tumour markers in serum are of minor value when used for detection of the disease in health screening protocols. Reflection of the course of disease: Tumour markers are of great value for monitoring the response to a given therapy and for early detection of relapse. In recent years, measurements of PSA has replaced PAP for this purpose. Prognostic indicator: Tumour markers in serum may also be used to indicate the biological activity of the tumour. Also for this purpose PSA appears to be a more reliable marker than PAP. General recommendation: For newly detected cases of prostatic carcinoma determination of a limited number of prognostic markers is recommended. If no treatment is instituted all these determinations may be repeated at an interval of about one year. Once treatment has been instituted assay of serum markers may be restricted to PSA alone and may be carried out at about six-monthly intervals. In protocolled clinical trials the intervals may be shortened.


Steroid profiles of transgenic tobacco expressing an Actinomyces 3-hydroxysteroid oxidase gene.
Previously, we have shown that the expression of a 3-hydroxysteroid-oxidase gene in transgenic tobacco initiated a series of biochemical events leading to the conversion of sterol to stanol. As a result, the plants maintained a diminished sterol pool and a modified relative sterol ratio but demonstrated no observable morphological abnormalities. The maintenance of normal higher plant physiology in the absence of particular sterols or in the presence of modified sterol ratios is controversial. In this report, we present additional biochemical and physiological characteristics of transgenic tobacco expressing an Actinomyces 3-hydroxysteroid-oxidase gene. The total steroid accumulated in the transgenic plants is 6-fold higher than in control plants and consists of sterol, 3-ketosteroid and stanol. The relative abundance of sterols within whole plant and individual organs is grossly altered as ethylated side chain sterols account for 99% of the total sterol pool in the transgenic tobacco. Stigmasterol is readily apparent in all tissues and cholesterol is found at measurable levels in specific organs, while campesterol and sitosterol are detected at trace levels in the transgenic plants. Stanols and 3-ketosteroids accumulate in all tissues and represent 77% of the measurable steroid pool in the transgenic plants. The sum of sterol, the respective 3-ketosteroid plus stanol provide a relative abundance of steroid, which is similar to the abundance of sterol accumulated in control tissue. In vitro photosynthetic electron transport measurements demonstrate altered activity of chloroplasts under a variety of reaction conditions, indicating a link between the modified steroid pool and a modulation of chloroplast membrane function.


Clinical, virologic and immunologic responses of children with advanced human immunodeficiency virus type 1 disease treated with protease inhibitors.
To determine the effects of combination antiretroviral therapy including a protease inhibitor (PI combination therapy) in children with advanced HIV-1 disease. An observational study of HIV-1 plasma RNA, lymphocyte subsets, delayed type hypersensitivity and physical growth after initiation of PI combination therapy. In nine children the median HIV-1 plasma RNA decreased 1.7 log10 (mean, 1.57; range, 0.7 to 2.2) following PI combination therapy and CD4 cells increased a median of 499 (mean, 528; range, 9 to 1088) cells/microl. A rebound of RNA, associated with the development of resistance to the PI, occurred in three subjects. Three of six children were no longer anergic and all nine achieved normal weight-growth velocities. Ritonavir was well-tolerated, despite its bitter taste; however, four of five children treated with indinavir developed renal complications. PI combination therapy in children with advanced HIV-1 disease was associated with a decrease in HIV-1 RNA, improved immunologic measures and normal or better weight gain. Of concern was the rebound in plasma HIV-1 associated with resistance to the PI observed in one-third of patients. This emphasizes the need for larger studies to define optimal PI containing regimens with long term efficacy in children.


Directed cell migration in co-cultures by topographic curvature for heterogeneous tissue engineering.
Placing cells in the proper position is important for tissue engineering. Previous works addressed this subject in the way of controlling cell migration by micro- or nano-patterning the substrates. However, the problem of changing spatial cell density freely under co-culture conditions is remaining. To solve this problem, in this work, we report that C2C12 spatial cell density changes by the patterning geometric boundary of the topographical structures. In 48 h after seeding cells, at the linear boundary (ridge-groove) structures, C2C12 Groove/Ridge ratio was under 0.70 both under monoculture conditions and under co-culture conditions. In contrast, at the combining the linear boundary and the round boundary (ridge-groove + hole) structures, the ratio was over 0.89 under both culture conditions. This our finding will provide a new device which enables to manipulate spatial cell density under co-culture conditions for heterogeneous tissue engineering.


Pains, joys, and secrets: nurse-led group therapy for older adults with depression.
This is the first study of nurse-led group therapy in Mexico. Forty-one depressed older adults with a median age of 71 participated in nurse-led cognitive behavioral group therapy once a week for 12 weeks. Participants' scores on the Patient Health Questionaire-9 showed mild to moderate improvement. Participants experienced positive results in personal growth, changing negative thoughts, and relationships with family. An important therapeutic factor was the support of fellow group members. The nurses experienced positive personal and professional growth. Difficulties included physician resistance and a too-rigid cognitive behavioral group therapy model. A combination of cognitive behavioral therapy and supportive group therapy is recommended.


[Hereditary neuropathy with pressure hypersensitivity or tomaculous neuropathy].
Hereditary neuropathy liability to pressure palsies is characterized by recurring accesses of painless paralysis at the level of various nerves likely to be compressed. This affection remains underdiagnosed because of its usually benign course, sometimes without any symptom. The diagnosis is supported by clinical and electrophysiological data associated with, in the majority of patients, a deletion of one of the alleles coding for protein PMP 22 on the level of the locus 17p11.2.


[Cerebrovascular Diseases and Autonomic Failure].
Cerebral vessels are innervated by sympathetic and parasympathetic nerves, as well as the trigeminal nerve. Under physiological conditions, neural regulation contributes to coupling of cerebral blood flow (CBF) and metabolism and autoregulation of CBF against systemic blood pressure. It also plays a key role in vasodilatation distal to narrowed vascular lesions associated with atherosclerosis, hyperperfusion syndrome that occurs after vascular reconstruction in patients with chronic ischemic diseases, reversible cerebral vasoconstriction syndrome, and migraine. Moreover, cerebrovascular disease can cause autonomic dysfunction; frontal lobe and brain stem lesions are known to result in urinary incontinence, mydriasis, and Horner's syndrome.


A story of two miracles: the impact of the discovery of insulin on pregnancy in women with diabetes mellitus.
Before the discovery of insulin in 1921, pregnancies in women with diabetes mellitus were a rarity because most reproductive-age patients died soon after diagnosis of this illness. In the limited number of pregnancies reported in the pre-insulin era, both perinatal and maternal mortality were approximately 50%, with stillbirths being the primary cause of perinatal deaths. Insulin treatment restored the fertility of women with diabetes and was associated with a marked reduction in maternal mortality. Women with more severe disease had the opportunity to become pregnant; however, their pregnancies frequently resulted in neonatal death due to prematurity. Therefore, perinatal mortality was not substantially reduced.


Effects of Propylene Oxide End Capping on Amination of Polyalkylene Glycols.
Polyalkylene glycols with two different end-capping groups of ethylene oxide (EO) and propylene oxide (PO) were used for amination to produce polyetheramine (PEA) on cobalt-based catalysts. Although it is known that the amination of secondary alcohol is more difficult than that of primary alcohol, PO end-capped block copolymers showed remarkably enhanced activity toward PEA and selectivity toward the primary amine compared to EO end-capped block copolymers.


Postnatal development of plasma amino acids in hyperphagic rats.
The effect of feeding a highly palatable high-energy cafeteria diet on individual amino acid levels in plasma during postnatal development of the rat has been evaluated and compared to chow-fed controls. The cafeteria diet selected by the rats was hypercaloric and hyperlipidic, with practically the same amount of carbohydrate as the control diet, and slightly hyperproteic. In response to cafeteria feeding, significant decreases were observed in plasma serine and cysteine along the period studied. Significant changes with age during the growth period were shown by cafeteria-fed animals, which were not observed in control rats. Citrulline levels were lower on days 10 and 14 in cafeteria pups than in chow pups. Methionine was highest on day 30. Threonine was also higher at days 20 and 30, as was valine but with a nadir at day 10. Lysine showed maximal values on days 14 and 30.


Nailfold capillary circulation in osteoarthritis.
Nailfold capillaries in 28 patients with OA affecting the distal interphalangeal joints were compared to 23 age- and sex-matched controls without OA. Patients with OA showed a significantly lower density of capillaries in their nailfolds and significantly more capillary morphological abnormalities including haemorrhage, 'drop out', dilatation and irregularity. There was a trend for OA patients to have warmer fingers with reduced finger to brachial blood pressure ratios. There were significant correlations between nailfold capillary numbers and average joint tenderness and between capillary morphological changes and joint swelling. These results reveal a relationship between interphalangeal joint OA and nailfold capillary abnormalities and density. As changes in microcirculation may be pertinent to the pathogenesis of OA, further studies which could explore possible causal relationships are warranted.


Drug Delivery System in the Treatment of Diabetes Mellitus.
Diabetes mellitus has been described as a chronic endocrine and metabolic disease, which is characterized by hyperglycemia and the coexistence of multiple complications. At present, the drugs widely applied in clinical treatment of diabetes mellitus mainly include insulin, insulin analogs, non-insulin oral hypoglycemic drugs and genetic drugs. Nevertheless, there is still no complete therapy strategy for diabetes mellitus management by far due to the intrinsic deficiencies of drugs and limits in administration routes such as the adverse reactions caused by long-term subcutaneous injection and various challenges in oral administration, such as enzymatic degradation, chemical instability and poor gastrointestinal absorption. Therefore, it is remarkably necessary to develop appropriate delivery systems and explore complete therapy strategies according to the characters of drugs and diabetes mellitus. Delivery systems have been found to be potentially beneficial in many aspects for effective diabetes treatment, such as improving the stability of drugs, overcoming different biological barriers in vivo to increase bioavailability, and acting as an intelligent automatized system to mimic endogenous insulin delivery and reduce the risk of hypoglycemia. This review aims to provide an overview related with the research advances, development trend of drug therapy and the application of delivery systems in the treatment diabetes mellitus, which could offer reference for the application of various drugs in the field of diabetes mellitus treatment.


Cyclic expression of the voltage-gated potassium channel KV10.1 promotes disassembly of the primary cilium.
The primary cilium, critical for morphogenic and growth factor signaling, is assembled upon cell cycle exit, but the links between ciliogenesis and cell cycle progression are unclear. KV10.1 is a voltage-gated potassium channel frequently overexpressed in tumors. We have previously reported that expression of KV10.1 is temporally restricted to a time period immediately prior to mitosis in healthy cells. Here, we provide microscopical and biochemical evidence that KV10.1 localizes to the centrosome and the primary cilium and promotes ciliary disassembly. Interference with KV10.1 ciliary localization abolishes not only the effects on ciliary disassembly, but also KV10.1-induced tumor progression in vivo Conversely, upon knockdown of KV10.1, ciliary disassembly is impaired, proliferation is delayed, and proliferating cells show prominent primary cilia. Thus, modulation of ciliogenesis by KV10.1 can explain the influence of KV10.1 expression on the proliferation of normal cells and is likely to be a major mechanism underlying its tumorigenic effects.


Stopping sports injuries in kids: an overview of the last year in publications.
Sports participation is common among children and adolescents throughout the United States; along with that participation comes risk of injury, sometimes serious. Over 4 million sports or recreational injuries are sustained by school-age children per year in the USA. This injury prevalence has led to significant interest in prevention strategies. In this review, we examine the last year of publications related to sports injury prevention in the pediatric population. Pediatric and adolescent athletes differ from adults in significant ways that often render them more susceptible to injury. Concussion is a particular problem, as are injuries to the thrower's elbow and injury to the female athlete's knee. Recognition, proper rest, and attention to mechanics may assist in decreasing the incidence and severity of these issues. Further inquiry into the nature, prevalence, causes, and, in particular, sequelae of pediatric sports injuries is required. In the interim, attention to proper technique, core and neuromuscular conditioning, and helmet use are important preventive measures; avoidance of overtraining and providing adequate rest for recovery are essential for pediatric and adolescent athletes.


Xanthogranulomatous pyelonephritis with calculus migration into the psoas abscess: an unusual complication.
Xanthogranulomatous pyelonephritis (XGP) is a rare variant of chronic pyelonephritis. It is characterized by progressive parenchymal destruction caused by chronic renal obstruction due to calculus, stricture, or rarely tumor, resulting in kidney function loss. Herein, we describe the case of a 36-year-old female who presented with left loin pain, left lower limb pain, and dysuria. On contrast-enhanced computed tomography (CECT), multiple abscesses and an obstructive staghorn calculus were depicted in the left kidney with the classical appearance of "Bear Paw Sign." An abscess with calculi was also present within the left psoas muscle. Though psoas muscle abscess in association with XGP was described, a ureteric fistula and calculi within the psoas muscle have not yet been reported in the literature. Left nephrostomy was performed, which came out to be positive for E. coli on culture. The patient underwent left nephrectomy, and the histopathological report of the surgical specimen confirmed XGP.


Saxagliptin enhances osteogenic differentiation in MC3T3-E1 cells, dependent on the activation of AMP-activated protein kinase α (AMPKα)/runt-related transcription factor-2 (Runx-2).
Osteoporosis is a metabolic bone disease commonly observed in the elderly, and its pathogenesis is associated with declined osteogenic differentiation. Osteogenic differentiation could be facilitated by the activation of the AMP-activated protein kinase (AMPK) pathway. Saxagliptin, an anti-diabetic agent with inhibitory effects against dipeptidyl peptidase 4 (DPP-4), has been recently reported to induce the activation of the AMPK pathway. The present study proposes to explore the function and mechanism of Saxagliptin in osteogenic differentiation. Osteogenic differentiation induction medium (ODIM) was utilized to induce osteogenic differentiation in MC3T3-E1 cells. Significantly increased mineral nodule formation, elevated alkaline phosphatase (ALP) activity, and upregulated expression of osteogenic marker genes activating transcription factor-4 (ATF-4), osteopontin (OPN), and type I collagen (Col1) were observed in ODIM-cultured MC3T3-E1 cells, all of which were further enhanced by the introduction of Saxagliptin. The elevated expression level of runt-related transcription factor-2 (Runx-2), an important transcriptional factor involved in the progression of osteogenic differentiation, in ODIM-cultured MC3T3-E1 cells was further promoted by Saxagliptin. The AMPK pathway in ODIM-cultured MC3T3-E1 cells was significantly activated by Saxagliptin, and the functions of Saxagliptin in promoting osteogenic differentiation were abolished by compound C, the inhibitor of the AMPK pathway. Conclusively, Saxagliptin enhanced osteogenic differentiation in MC3T3-E1 cells, dependent on the activation of AMPKα/RUNX-2.