[Effect of dangua recipe on glycolipid metabolism and VCAM-1 and its mRNA expression level in Apo E(-/-) mice with diabetes mellitus].
To study the effect of Dangua Recipe (DGR) on glycolipid metabolism, vascular cell adhesion molecule-1 (VCAM-1) and its mRNA expression level of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis, thus revealing its partial mechanism for curing diabetes mellitus (DM) with angiopathy. Diabetic model was prepared by peritoneally injecting streptozotocin (STZ) to Apo E(-/-) mouse. Totally 32 modeled mice were stratified by body weight, and then divided into 4 groups referring to blood glucose levels from low to high by random digit table, i.e., the model group (MOD, fed with sterile water, at the daily dose of 15 mL/kg), the DGR group (fed with DGR at the daily dose of 15 mL/kg), the combination group (COM, fed with DGR at the daily dose of 15 mL/kg and pioglitazone at the daily dose of 4.3 mg/kg), and the pioglitazone group (PIO, at the daily dose of 4.3 mg/kg), 8 in each group. Another 8 normal glucose C57 mouse of the same age and strain were recruited as the control group. All interventions lasted for 12 weeks by gastrogavage. The fasting blood glucose (FBG), body weight, food intake, water intake, skin temperature, the length of tail, and the degree of fatty liver were monitored. The hemoglobin A1c (HbA1c), total cholesterol (TC), and LDL-C were determined. Endothelin-1 (ET-1) was determined by radioimmunoassay. Nitrogen monoxidum (NO) was determined by nitrate reductase. The kidney tissue VCAM-1 level was analyzed with ELISA. The expression of VCAM-1 mRNA in the kidney tissue was detected with real time quantitative PCR. Compared with the control group, the body weight and food intake decreased, water intake increased in all the other model groups (P < 0.05). Besides, the curve of blood glucose was higher in all the other model groups than in the control group (P < 0.01). Compared with the model group, the body weight increased; levels of HbAlc, TC, LDL-C, ET-1, and VCAM-1 were significantly lower; and skin temperature was higher in the DGR group (P < 0.05, P < 0.01). Compared with the PIO group, body weight, the increment of body weight, FBG, TC, and LDL-C were lower (P < 0.05, P < 0.01); food intake and water intake increased more and the tail length was longer in the DRG group (P < 0.01). There was no statistical difference in the level of NO among groups. The degree of fatty liver in the model group was significantly severer than that in the control group (P < 0.05). It was obviously alleviated in the DGR group (P < 0.05) when compared with the model group and the PIO group (P < 0.05, P < 0.01). But it was severer in the PIO group than in the model group (P < 0.01). The degree of fatty liver in the combination group ranged between that of the DGR group and the PIO group (P < 0.05). The level of VCAM-1 mRNA expression was significantly lower in the DGR group than in the model group, the PIO group, and the combination group (P < 0.05). DGR had effect in lowering blood glucose and blood lipids, and fighting against fatty liver of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis. DGR played an effective role in preventing and treating DM with angiopathy by comprehensively regulating glycolipid metabolism and promoting the vascular function.


Multicolour whole-mount in situ hybridization to Drosophila embryos.
We report an extended whole-mount in situ hybridization procedure for Drosophila embryos. By using probes labelled with digoxigenin, fluorescein and biotin, respectively, this protocol allows the detection in three colours of RNAs derived from three different genes. Hybridized probes are detected by consecutive staining with appropriate alkaline phosphatase conjugates using different chromogenic substrate combinations, and serial removal of the antibody conjugates by low pH washes.


Skeletal and hormonal responses to vitamin D supplementation during sunlight deprivation in Antarctic expeditioners.
Sunlight deprivation results in vitamin D deficiency but serum vitamin D levels can be maintained above 50 nmol/L when supplemented with 50,000 IU at least every alternate month. Antarctic expeditioners are exposed to prolonged sunlight deprivation resulting in vitamin D deficiency. We hypothesised that monthly dosing of 50,000 IU vitamin D (~1,600 IU daily) will increase serum 25-hydroxyvitamin D (25(OH)D), suppress parathyroid hormone (PTH) and improve bone mineral density (BMD), 50,000 IU alternate months (~800 IU daily) will maintain these measures, while a single 50,000 IU dose pre-departure (~1,00 IU daily) will not be protective. This was a randomised double-blind study involving 110 healthy adults: 91 males, mean age 41 years (range 24-65 years) working in Antarctica for up to 12 months, who we administered 50,000 IU vitamin D3 monthly, alternate months or a single dose pre-departure. Serum 25(OH)D, PTH, osteocalcin, CTx and calcium were assessed at baseline, mid- and end of expedition. Proximal femur and lumbar spine BMD were assessed pre- and post-expedition. Baseline 25(OH)D was 59 ± 14 nmol/L. By mid-expedition, 25(OH)D increased by 7 nmol/L in those supplemented monthly (p < 0.05) and remained unchanged in those supplemented in alternate months. In those given a single dose pre-departure, 25(OH)D decreased by 8 nmol/L (p < 0.05) and PTH increased by 27% (p < 0.09). Serum osteocalcin increased by ~22% in all groups but BMD remained unchanged. If serum 25(OH)D was >50 nmol/L at baseline, 25(OH)D was maintained above this level with all regimens. If 25(OH)D was <50 nmol/L at baseline, monthly or alternate month regimens were needed to achieve levels >50 nmol/L, the single pre-departure dose was ineffective. During sunlight deprivation of up to 12 months, serum 25(OH)D levels can be maintained above 50 nmol/L when expeditioners are provided with 50,000 I U at least every alternate month.


A Forensic Disassembly of the BIS Monitor.
The bispectral index (BIS) monitor has been available for clinical use for >20 years and has had an immense impact on academic activity in Anesthesiology, with >3000 articles referencing the bispectral index. Despite attempts to infer its algorithms by external observation, its operation has nevertheless remained undescribed, in contrast to the algorithms of other less commercially successful monitors of electroencephalogram (EEG) activity under anesthesia. With the expiration of certain key patents, the time is therefore ripe to examine the operation of the monitor on its own terms through careful dismantling, followed by extraction and examination of its internal software. An A-2000 BIS Monitor (gunmetal blue case, amber monochrome display) was purchased on the secondary market. After identifying the major data processing and storage components, a set of free or inexpensive tools was used to retrieve and disassemble the monitor's onboard software. The software executes primarily on an ARMv7 microprocessor (Sharp/NXP LH77790B) and a digital signal processor (Texas Instruments TMS320C32). The device software can be retrieved directly from the monitor's hardware by using debugging interfaces that have remained in place from its original development. Critical numerical parameters such as the spectral edge frequency (SEF), total power, and BIS values were retraced from external delivery at the device's serial port back to the point of their calculation in the extracted software. In doing so, the locations of the critical algorithms were determined. To demonstrate the validity of the technique, the algorithms for SEF and total power were disassembled, comprehensively annotated and compared to their theoretically ideal behaviors. A bug was identified in the device's implementation of the SEF algorithm, which can be provoked by a perfectly isoelectric EEG. This article demonstrates that the electronic design of the A-2000 BIS Monitor does not pose any insuperable obstacles to retrieving its device software in hexadecimal machine code form directly from the motherboard. This software can be reverse engineered through disassembly and decompilation to reveal the methods by which the BIS monitor implements its algorithms, which ultimately must form the definitive statement of its function. Without further revealing any algorithms that might be considered trade secrets, the manufacturer of the BIS monitor should be encouraged to release the device software in its original format to place BIS-related academic literature on a firm theoretical foundation and to promote further academic development of EEG monitoring algorithms.


Management and positive outcome of skull-base ossifying fibroma: a case report.
The ossifying fibroma is a benign fibro-osseous tumor rarely affecting the skull base. The incidence of ossifying fibroma itself is uncommon. It is considered to be an aggressive and fast-growing bone lesion. Early detection and complete surgical removal are essential to deal with its aggressive nature and recurrence. We report a case of a 20-year-old man admitted for the management of ossifying fibroma of the orbital roof extending inside the orbit mimicking meningioma and revealed by a progressive proptosis and headache. The patient underwent surgery for the subtotal removal of the tumor with its frontal infiltration with a good outcome. All meningiomas like tumors are not meningiomas and other tumors such as ossifying fibroma might be mistaken for meningioma and even get confirmation from the pathological anatomy study. Need be for these tumors to be looked at more closely for better therapeutic decision-making.


Mutation pressure shapes codon usage in the GC-Rich genome of foot-and-mouth disease virus.
Foot-and-mouth disease (FMD) is economically the most important viral-induced livestock disease worldwide. In this study, we report the results of a survey of codon usage bias of FMD virus (FMDV) representing all seven serotypes (A, O, C, Asia 1, SAT 1, SAT 2, and SAT 3). Correspondence analysis, a commonly used multivariate statistical approach, was carried out to analyze synonymous codon usage bias. The analysis showed that the overall extent of codon usage bias in FMDV is low. Furthermore, the good correlation between the frequency of G + C at the synonymous third position of sense codons (GC3S) content at silent sites of each sequence and codon usage bias suggested that mutation pressure rather than natural (translational) selection is the most important determinant of the codon bias observed. In addition, other factors, such as the lengths of open reading frame (ORF) and the hydrophobicity of genes also influence the codon usage variation among the genomes of FMDV in a minor way. The result of phylogenetic analyses based on the relative synonymous codon usage (RSCU) values indicated a few obvious phylogenetic incongruities, which suggest that more FMDV genome diversity may exist in nature than is currently indicated. Our work might give some clues to the features of FMDV genome and some evolutionary information of this virus.


Advances in diagnosis, treatment, and management of orbital and periocular Wegener's granulomatosis.
Ophthalmologists are often in a position to diagnose Wegener's granulomatosis and prevent significant morbidity. The past 2 years have seen advances in diagnosis and management strategies for this condition. Orbital magnetic resonance imaging and histologic profiles have been better characterized. Perhaps the greatest advance has been the recognition of promising therapeutic alternatives to the current standard cytotoxic protocol. Trimethoprim-sulfamethoxazole or methotrexate may be valuable in selected patients with limited forms of Wegener's granulomatosis. Finally, new insights into the mechanisms of disease activation and tissue injury may lead to better treatment and long-term prognosis.


Osteoimmunology: The Regulatory Roles of T Lymphocytes in Osteoporosis.
Immune imbalance caused bone loss. Osteoimmunology is emerging as a new interdisciplinary field to explore the shared molecules and interactions between the skeletal and immune systems. In particular, T lymphocytes (T cells) play pivotal roles in the regulation of bone health. However, the roles and mechanisms of T cells in the treatment of osteoporosis are not fully understood. The present review aims to summarize the essential regulatory roles of T cells in the pathophysiology of various cases of osteoporosis and the development of T cell therapy for osteoporosis from osteoimmunology perspective. As T cell-mediated immunomodulation inhibition reduced bone loss, there is an increasing interest in T cell therapy in an attempt to treat osteoporosis. In summary, the T cell therapy may be further pursued as an immunomodulatory strategy for the treatment of osteoporosis, which can provide a novel perspective for drug development in the future.


Cholestatic jaundice associated with chlorozotocin.
Clinical and pathologic studies of three cases of drug-induced cholestatic jaundice associated with the new antineoplastic agent chlorozotocin are presented. All three patients had received intermittent treatment with high doses of chlorozotocin. The recognition of this unusual form of hepatotoxicity is important in view of the many possible causes of jaundice in cancer patients.


Retinopathy of Prematurity as Multidisciplinary Approach, a Pediatricians Standpoint, and Practice.
This study aims to measure the knowledge levels toward retinopathy of prematurity (ROP) among pediatricians covering neonatal intensive care units (NICUs) in the major hospitals in Tabuk, Saudi Arabia. To our knowledge, this is the first report to assess the awareness level of ROP in the NICU pediatricians in the region. This is a quantitative, non-experimental, cross-sectional, descriptive study using self-administered electronic questionnaires to assess the knowledge level among NICU pediatricians at the main hospitals of Tabuk city. We used a self-administer online validated knowledge, attitude, and practice (KAP) questionnaire. A scoring system was implemented in the data analysis, depending on the correct chosen answers on the KAP questionnaire, to present the ROP knowledge level in the participants. The study included 41 NICU pediatricians. Most of the participants' age exceeded 40 years (51.2%). The majority were recruited from either King Salman Military hospital (34.1%) or King Khalid hospital (31.7%). The average frequency of preterm infants seen per month exceeded 15 infants among 41.4% of the respondents. Most pediatricians recognized the important treatment modalities available for ROP (92.7%); however, only 24.4% of them could recognize that 32 weeks or less is the gestational age of the screening criteria for ROP. The overall knowledge score ranged between 4 and 10, out of a possible maximum of 12 with a mean ± SD of (6.68±1.47). The majority (75.6%) believe that the ROP treatment can successfully prevent blindness. Our study demonstrated that the NICU pediatricians have good knowledge about the treatment modalities of ROP. However, their knowledge about the inclusion criteria of ROP screening was insufficient. Thus, we highlighted the necessity of raising the awareness level and the strict application of the clinical guidelines among NICU pediatricians and healthcare workers involved in managing ROP.


Acute pain management services: a comparison between Air Force and U.S. hospitals.
The purpose of this descriptive study was to assess the prevalence of acute pain management services (APMS) in Air Force medical facilities. There are no published reports on the current status of Air Force pain programs. This study used a telephone survey to all facilities worldwide that house an anesthesia department. Anesthesia providers in charge of pain services or department chiefs were interviewed from December 1996 to May 1997. Respondents were asked questions related to the initiation of a formal APMS, components, and familiarity with the Agency for Health Care Policy and Research guidelines on pain management. Data analysis described current practices and used chi 2 analysis to compare results with a national study of U.S. hospitals. Air Force anesthesia departments (45%) had established as many acute pain services as U.S. hospitals (42%). Formal pain programs are becoming more prevalent in Air Force hospitals. These findings suggest an increased awareness of the need for pain management and future establishment of pain programs.


Increased Neutrophil Respiratory Burst Predicts the Risk of Coronary Artery Lesion in Kawasaki Disease.
Background: Kawasaki diseases (KD) is a febrile systemic vasculitis in infants associated with coronary aneurysm. The etiology of KD remains unclear. Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS). Brain natriuretic peptide (BNP) is a substantial modulator of neutrophil activation to regulate ROS production. It is increasingly released from the myocardium in heart failure and myocardial inflammatory states. Objective: The purpose of this study was to explore the potential role of neutrophil respiratory burst in the pathogenesis of coronary artery lesions (CAL) in KD. Materials and Methods: A total of 78 children were enrolled. Of all the cases, 20 cases are healthy control (HC), 20 are with coronary artery lesion (CAL), and 38 are with non-coronary artery lesion (NCAL). The activation ratio of neutrophils was evaluated by flow cytometry. In addition, plasma levels of BNP were detected. Results: Our results showed that the activation ratio of neutrophils in KD with CAL is significantly higher than the other two groups (HC and NCAL). Besides, the plasma levels of BNP in KD (with or without CAL) were higher than that in HC. Conclusions: These findings suggested that neutrophil respiratory burst may play a significant role in the pathogenesis of CAL, and predicts the risk of CAL in Kawasaki disease.


[YAP regulates the proliferation and modifies the sensitivity to sorafenib in hepatocellular carcinoma cells].
Objective: To detect the expression level of YES-associated protein 1 (YAP) in hepatocellular carcinoma (HCC) cell lines and investigate its effects on the proliferation activity and the sensitivity to sorafenib in HCC cells. Methods: Western blot was used to detect the protein expression levels of YAP in SMMC-7721, SK-Hep-1, HepG-2, Huh7 and the normal liver cell line L-O2. YAP specific small interfering RNA (si-YAP) or YAP expression plasmid were transfected in SK-Hep-1 or Huh7 cells, respectively. Cell counting kit-8 (CCK-8) test was used to detect the cell proliferation activity and the cell cycle test was conducted by flow cytometry. SK-Hep-1 and SK-Hep-1 si-YAP cells were subcutaneously injected into the nude mice which were sequentially treated by intragastric administration of sorafenib, and the tumor growth in vivo were observed and compared. Results: The expression of YAP was upregulated in HCC cell lines. Deletion of YAP expression significantly decreased the survival rate of SK-Hep-1 cells [(78.5±0.3)% vs (92.3±0.2)%, P=0.025]. Knockdown of YAP significantly increased the percentage of G(0)/G(1)-phase cells [ (65.4±3.3) % vs (55.7±3.4) %, P=0.039]. On the contrary, upregulation of the YAP expression in Huh7 cells significantly increased the cell survival rate [(81.2±1.3)% vs (62.5±1.1)%, P=0.013] and reduced the percentage of G(0)/G(1)-phase cells [(38.2±3.8)% vs (48.8±2.9)%, P=0.019]. The survival rate of SK-Hep-1 cells treated by si-YAP combined with sorafenib was (31.13±1.79)%, significantly lower than (48.87±0.58) % of SK-Hep-1 cells treated by sorafenib alone (P=0.001), while overexpression of YAP attenuated the inhibitory effect of sorafenib on the survival of Huh7 cells [(69.98±2.94) % vs (53.53±1.93)%, P=0.001]. The tumor weights of SK-Hep-1 group, sorafenib alone group, SK-Hep-1 si-YAP group and SK-Hep-1 si-YAP combined with sorafenib group were (0.96±0.08) g, (0.62±0.08) g, (0.70±0.06) g and (0.27±0.02) g, respectively. The tumor weights of sorafenib alone group and SK-Hep-1 si-YAP group were significantly lower than that of SK-Hep-1 group (P=0.012 and P=0.031, respectively). The tumor weight of SK-Hep-1 si-YAP combined with sorafenib group was significantly lower than that of SK-Hep-1 si-YAP group (P=0.001). Conclusions: The expression of YAP is upregulated in HCC cell lines, which regulates the proliferation, cell cycle, and sensitivity to sorafenib of HCC cells. YAP is a potential molecular target for HCC treatment.


Lignocellulolysis by ascomycetes (fungi) of a saltmarsh grass (smooth cordgrass).
Lignocellulose (LC) makes up greater than 70% of the mature shoots of the prodigiously photosynthetically productive saltmarsh grass Spartina alterniflora. Naturally decaying shoots of this cordgrass were examined by transmission electron microscopy (after high-pressure freezing and freeze-substitution) as a means of directly detecting lysis of the LC-rich tissues. Portions of the cordgrass were selected that contained ascomata (sexual reproductive structures) of only one of each of four species of fungi (Kingdom Fungi; Subdivision Ascomycotina): Phaeosphaeria spartinicola and Buergenerula spartinae from leaf blades, Phaeosphaeria spartinae from leaf sheaths, and Passeriniella obiones from naked stems. All four of the ascomycetes were LC-lytic. Phaeosphaeria spartinicola caused both thinning of LC-rich secondary walls of fiber cells from cell lumina outwards (type 2 soft rot, akin to white rot) and digestion extending from hyphae within longitudinal cavities in the secondary walls (type 1 soft rot). The other three species caused either one or the other type of soft rot. Bacterial erosion of cordgrass cells was found only in the samples of naked stems. Ascomycetous decomposers of standing-dead grasses may have potential for biotechnological applications involving alterations of lignocellulose or toxic polyphenolic substances.


Relationship between body weight, body position, support surface, and tissue interface pressure at the sacrum.
This descriptive, comparative study examined the relationship between three body positions, body weight, and tissue interface pressure measurement on three support surfaces among residents who were 65 years of age or older. The support surfaces included the Sof. Care bed cushion, Biogard foam mattress, and hospital mattress. Subjects included 12 ideal body-weight and six less-than-ideal body-weight individuals from a long-term care facility in a Mid-western state. Results indicated no significant difference in sacral tissue interface difference between ideal body weight and less-than-ideal body weight subjects. However, the sacral measurements were significantly greater in the supine position than those taken in the Fowler's and semi-Fowler's positions. A significant interaction was found between position and support surface with subjects in Fowler and semi-Fowler positions on the Sof. Care Surface exhibiting the lowest mean tissue interface pressure at the sacrum.


Immunological characterization of peptidyl-glycine-alpha-amidating monooxygenases.
Antibodies to the soluble form of the copper-containing enzyme, peptidyl-glycine-alpha-amidating monooxygenase isolated from secretory granules of bovine pituitary anterior lobes were found to belong to immunoglobulin G1. The antibodies were used to study the subcellular distribution of the enzyme in this tissue, and positive tests were found only for granular and cytosol fractions. The antibodies do not crossreact with other copper-containing systems of secretory granules, such as neurocuprein and dopamine-beta-monooxygenase. It was shown that the antibodies give the crossreaction with the enzyme isolated from secretory granules of bovine pituitary anterior lobes, cardiac atria, pancreas and adrenal medulla, indicating the antigenic identity of the enzyme from secretory granules of different glands.


Bleeding from an Unruptured Cerebral Aneurysm following the Local Intra-arterial Administration of Urokinase: A Case Report.
A 57-year-old woman with a wide-necked anterior communicating artery (Acom) aneurysm underwent stent-assisted coiling (SAC) due to aneurysm enlargement. Dual antiplatelet therapy was initiated 7 days before the operation, and systemic heparinization was performed while maintaining an activated clotting time (ACT) of approximately 300 s during the procedure. SAC was performed using a laser-cut closed-cell stent and bare platinum coils. At the end of the procedure, the Acom and right anterior cerebral artery (ACA) were occluded by in-stent thrombosis. Following local intra-arterial administration of 480000 U of urokinase, the Acom and right ACA were recanalized, accompanied by extravasation around the Acom aneurysm. A computed tomography (CT) scan revealed a right frontal hematoma, which did not enlarge after the administration of protamine sulfate. The hematoma disappeared spontaneously, and the patient recovered without any neurological deficits. Local administration of urokinase is an effective treatment for in-stent thrombosis. However, because the devices for SAC may cause mechanical injuries to the aneurysms, urokinase should be used cautiously for cerebral aneurysms, even if unruptured.


Formation of one-dimensional metal-water chain containing cyclic water hexamers.
Cyclic water hexamers containing 1-D metal--water chains have been observed in the complexes of [M(H(2)biim)(2)(OH(2))(2)](ina)(2) x 4H(2)O [M = Zn (1) and Co (2), H(2)biim = 2,2'-biimidazole, ina = isoniconate]. The water clusters are trapped by the cooperative association of coordination interactions as well as hydrogen bonds.


Outcomes among newborns with total serum bilirubin levels of 25 mg per deciliter or more.
The neurodevelopmental risks associated with high total serum bilirubin levels in newborns are not well defined. We identified 140 infants with neonatal total serum bilirubin levels of at least 25 mg per deciliter (428 micromol per liter) and 419 randomly selected controls from a cohort of 106,627 term and near-term infants born from 1995 through 1998 in Kaiser Permanente hospitals in northern California. Data on outcomes were obtained from electronic records, interviews, responses to questionnaires, and neurodevelopmental evaluations that had been performed in a blinded fashion. Peak bilirubin levels were between 25 and 29.9 mg per deciliter (511 micromol per liter) in 130 of the newborns with hyperbilirubinemia and 30 mg per deciliter (513 micromol per liter) or more in 10 newborns; treatment involved phototherapy in 136 cases and exchange transfusion in 5. Follow-up data to the age of at least two years were available for 132 of 140 children with a history of hyperbilirubinemia (94 percent) and 372 of 419 controls (89 percent) and included formal evaluation at a mean (+/-SD) age of 5.1+/-0.12 years for 82 children (59 percent) and 168 children (40 percent), respectively. There were no cases of kernicterus. Neither crude nor adjusted scores on cognitive tests differed significantly between the two groups; on most tests, 95 percent confidence intervals excluded a 3-point (0.2 SD) decrease in adjusted scores in the hyperbilirubinemia group. There was no significant difference between groups in the proportion of children with abnormal neurologic findings on physical examination or with documented diagnoses of neurologic abnormalities. Fourteen of the children with hyperbilirubinemia (17 percent) had "questionable" or abnormal findings on neurologic examination, as compared with 48 controls (29 percent; P=0.05; adjusted odds ratio, 0.47; 95 percent confidence interval, 0.23 to 0.98; P=0.04). The frequencies of parental concern and reported behavioral problems also were not significantly different between the two groups. Within the hyperbilirubinemia group, those with positive direct antiglobulin tests had lower scores on cognitive testing but not more neurologic or behavioral problems. When treated with phototherapy or exchange transfusion, total serum bilirubin levels in the range included in this study were not associated with adverse neurodevelopmental outcomes in infants born at or near term.


Binding of GAPR-1 to negatively charged phospholipid membranes: unusual binding characteristics to phosphatidylinositol.
Golgi-Associated Plant Pathogenesis-Related protein 1 (GAPR-1) is a mammalian protein that belongs to the superfamily of plant pathogenesis-related proteins group 1 (PR-1). GAPR-1 strongly associates with lipid rafts at the cytosolic leaflet of the Golgi membrane. The myristoyl moiety at the N-terminus of GAPR-1 contributes to membrane binding but is not sufficient for stable membrane anchorage. GAPR-1 is positively charged at physiological pH, which allows for additional membrane interactions with proteins or lipids. To determine the potential contribution of lipids to membrane binding of GAPR-1, we used a liposome binding assay. Here we report that non-myristoylated GAPR-1 stably binds liposomes that contain the negatively charged lipids phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, or phosphatidic acid. GAPR-1 displays the highest preference for phosphatidic acid-containing liposomes. In contrast, lysozyme, which contains a similar surface charge, did not bind to these liposomes, except for a weak membrane association with PA-containing liposomes. Interestingly, GAPR-1 binds to phosphatidylinositol with unusual characteristics. Denaturation or organic extraction of GAPR-1 does not result in dissociation of phosphatidylinositol from GAPR-1. The association of phosphatidylinositol with GAPR-1 results in a diffuse gel-shift in SDS-PAGE. Mass spectrometric analysis of gel-shifted GAPR-1 showed the association of up to 3 molecules of phosphatidylinositol with GAPR-1. These results suggest that the lipid composition contributes to the GAPR-1 binding to biological membranes.


Characterization of the Formation and Distribution of Photosynthetic Products by Sedum praealtum Chloroplasts.
Photoassimilation of (14)CO(2) by intact chloroplasts from the Crassulacean acid metabolism plant Sedum praealtum was investigated. The main water-soluble, photosynthetic products were dihydroxyacetone phosphate (DHAP), glycerate 3-phosphate (PGA), and a neutral saccharide fraction. Only a minor amount of glycolate was produced. A portion of neutral saccharide synthesis was shown to result from extrachloroplastic contamination, and the nature of this contamination was investigated with light and electron microscopy. The amount of photoassimilated carbon partitioned into starch increased at both very low and high concentrations of orthophosphate. High concentrations of exogenous PGA also stimulated starch synthesis.DHAP and PGA were the preferred forms of carbon exported to the medium, although indirect evidence suported hexose monophosphate export. The export of PGA and DHAP to the medium was stimulated by high exogenous orthophosphate, but depletion of chloroplastic reductive pentose phosphate intermediates did not occur. As a result only a relatively small inhibition in the rate of CO(2) assimilation occurred.The rate of photoassimilation was stimulated by exogenous PGA, ribose 5-phosphate, fructose 1,6-bisphosphate, fructose 6-phosphate, and glucose 6-phosphate. Inhibition occurred with phosphoenolpyruvate and high concentrations of PGA and ribose 5-phosphate. PGA inhibition did not result from depletion of chloroplastic orthophosphate or from inhibition of ribulose 1,5-bisphosphate carboxylase. Exogenous PGA and phosphoenolpyruvate were shown to interact with the orthophosphate translocator.


Mapping the expression of an ANK3 isoform associated with bipolar disorder in the human brain.
The gene ankyrin-3 (ANK3) has been consistently associated with bipolar disorder (BD) in several genome-wide association studies (GWAS). The exact molecular mechanisms underlying this genetic association remain unknown. The discovery of a loss-of-function variant (rs41283526*G) in an alternatively spliced exon (ENSE00001786716) with a protective effect, suggested that elevated expression of this particular isoform could be a risk factor for developing the disorder. We developed a novel approach for measuring the expression level of all splice forms at a challenging genetic locus using a combination of droplet digital PCR and high-throughput sequencing of indexed PCR amplicons. The combined method was performed on a large collection of 568 postmortem brain samples of BD and SCZ cases and controls. We also studied the expression of the splice forms in a child-development cohort of 41 healthy males. We found that our approach can quantify the splice forms in brain samples, although with less precision than ddPCR. We detected highly significant differences in expression of splice forms and transcription start sites between brain regions, notably with higher expression of the BD-associated isoform in the corpus callosum compared to frontal tissue (mean fold change = 1.80, p < 1e-4). Although the patients in our sample expressed the BD-associated splice form at a similar level to controls, adolescents in our child-development cohort had a clearly higher expression level than younger children (mean fold change = 1.97, p = 5e-3). These results suggest that this ANK3 splice form may play a role in the myelin maturation of the human brain.


Alcohol and the pancreas.
This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The presentations were (1) Phenotypic alteration of myofibroblast during ethanol-induced pancreatic injury: its relation to bFGF, by Masahiko Nakamura, Kanji Tsuchimoto, and Hiromasa Ishii; (2) Activation of pancreatic stellate cells in pancreatic fibrosis, by Paul S. Haber, Gregory W. Keogh, Minoti V. Apte, Corey S. Moran, Nancy L. Stewart, Darrell H.G. Crawford, Romano C. Pirola, Geoffrey W. McCaughan, Grant A. Ramm, and Jeremy S. Wilson; (3) Pancreatic blood flow and pancreatic enzyme secretion on acute ethanol infusion in anesthetized RAT, by H. Nishino, M. Kohno, R. Aizawa, and N. Tajima; (4) Genotype difference of alcohol-metabolizing enzymes in relation to chronic alcoholic pancreatitis between the alcoholic in the National Institute on Alcoholism and patients in other general hospitals in Japan, by K. Maruyama, H. Takahashi, S. Matsushita, K. Okuyama, A. Yokoyama, Y. Nakamura, K. Shirakura, and H. Ishii; and (5) Alcohol consumption and incidence of type 2 diabetes, by Katherine M. Conigrave, B. Frank Hu, Carlos A. Camargo Jr, Meir J. Stampfer, Walter C. Willett, and Eric B. Rimm.


Obstetrics and fecal incontinence.
Anal incontinence (AI) can be a debilitating condition for women following vaginal delivery. Operative vaginal delivery and anal sphincter laceration are important risk factors for the development of postpartum AI. Obtaining a comprehensive delivery history, along with a thorough physical examination of the perineum, vagina and rectum may aid the clinician in the diagnosis of an anal sphincter defect. Sonographic imaging can also assist in identifying sphincter defects. The treatment of AI may include a combination of dietary modification, medications that promote constipation, pelvic floor physical therapy, biofeedback, anal sphincteroplasty, and/or sacral neuromodulation.


The geographic distribution of the putative agent of epizootic bovine abortion in the tick vector, Ornithodoros coriaceus.
Epizootic bovine abortion (EBA), also known as "foothill abortion", is a vector borne disease of beef cattle that graze in the mountainous regions of California, southern Oregon and western Nevada transmitted by the argasid tick Ornithodoros coriaceus. Recently, the putative agent of EBA was identified as a novel Deltaproteobacter in the order Myxococcales. In this study, a TaqMan real-time PCR (TM-PCR) protocol specific to the putative EBA agent was developed. The new real-time TM-PCR assay functioned sensitively and specifically to detect pathogen DNA in field-collected O. coriaceus ticks. The assay had an analytical sensitivity of a single plasmid copy and, when evaluated with a collection of tick-borne pathogens, yielded a positive PCR-result only for the agent of EBA. Use of the TM-PCR represents an effective tool for rapid and highly sensitive assessment of environmental risk and spatial and statistical analysis to highlight areas where there may be increased risk for EBA in susceptible cattle.


Anthrax toxin-mediated delivery of the Pseudomonas exotoxin A enzymatic domain to the cytosol of tumor cells via cleavable ubiquitin fusions.
Anthrax toxin proteins from Bacillus anthracis constitute a highly efficient system for delivering cytotoxic enzymes to the cytosol of tumor cells. However, exogenous proteins delivered to the cytosol of cells are subject to ubiquitination on lysines and proteasomal degradation, which limit their potency. We created fusion proteins containing modified ubiquitins with their C-terminal regions fused to the Pseudomonas exotoxin A catalytic domain (PEIII) in order to achieve delivery and release of PEIII to the cytosol. Fusion proteins in which all seven lysines of wild-type ubiquitin were retained while the site cleaved by cytosolic deubiquitinating enzymes (DUBs) was removed were nontoxic, apparently due to rapid ubiquitination and proteasomal degradation. Fusion proteins in which all lysines of wild-type ubiquitin were substituted by arginine had high potency, exceeding that of a simple fusion lacking ubiquitin. This variant was less toxic to nontumor tissues in mice than the fusion protein lacking ubiquitin and was very efficient for tumor treatment in mice. The potency of these proteins was highly dependent on the number of lysines retained in the ubiquitin domain and on retention of the C-terminal ubiquitin sequence cleaved by DUBs. It appears that rapid cytosolic release of a cytotoxic enzyme (e.g., PEIII) that is itself resistant to ubiquitination is an effective strategy for enhancing the potency of tumor-targeting toxins. Bacterial toxins typically have highly efficient mechanisms for cellular delivery of their enzymatic components. Cytosolic delivery of therapeutic enzymes and drugs is an important topic in molecular medicine. We describe anthrax toxin fusion proteins containing ubiquitin as a cytosolic cleavable linker that improves the delivery of an enzyme to mammalian cells. The ubiquitin linker allowed modulation of potency in cells and in mice. This effective strategy for enhancing the intracellular potency of an enzyme may be useful for the cytosolic delivery and release of internalized drugs.


Benefits and challenges of health information systems for operations research: an illustrative example to improve surgical scheduling.
Operations research (OR) is playing an increasing role in the support of many health care initiatives. However one of the main challenges facing OR practitioners is the availability and the integrity of operations data. Hospital information systems (HIS) are often designed with a clinical or accounting focus and may lack the data necessary for operational studies. In this paper, we illustrate the data processing methods and data challenges faced by our team during a study of surgical scheduling practices at the Vancouver Island Health Authority. We also provide some general recommendations to improve HIS from an operations perspective. In general, more integration between operations researchers and HIS specialists are required to support ongoing operational improvements in the health care sector.


Genetic Association of PARP15 Polymorphisms with Clinical Outcome of Acute Myeloid Leukemia in a Korean Population.
Some members of the poly ADP-ribose polymerase (PARP) protein family have been regarded as targets for the therapeutic inhibition of cancer. Among these PARP genes, poly ADP-ribose polymerase family, member 15 (PARP15) is a candidate gene for cancer development due to its ability to regulate gene transcription and its reported association with apoptosis. The current study investigated the possible association between PARP15 single-nucleotide polymorphisms and the risk of acute myeloid leukemia (AML). In addition, we analyzed the effects of the PARP15 polymorphisms on the clinical phenotypes associated with cytosine arabinose (AraC) chemotherapy in AML patients. Ten PARP15 polymorphisms were genotyped via TaqMan assay in a total of 344 Korean subjects, including 103 AML patients and 241 normal controls. The genetic effects of the polymorphisms on the risk of AML and the clinical phenotypes were analyzed using Statistical Analysis System (SAS) software. The results from a Cox regression analysis for overall survival revealed that two polymorphisms were associated with increased overall survival and the signal for rs17208928 was retained after correcting for multiple tests (pcorr < 0.05). These results suggest the possibility that the PARP15 gene may be a potential therapeutic target in AML patients although much larger scale studies are needed for validation.


[Implant-supported bridges in the edentulous jaw. Clinical aspects of a simple treatment concept].
Clinical aspects of a simple treatment concept with fixed prostheses in the edentulous jaw are described. Fixed implant-supported reconstructions in the edentulous jaw require multiple implants, are technically complex, aesthetically demanding and metal-ceramic solutions are expensive. Specific surgical techniques to enhance the hard and soft tissue conditions become often necessary. Thus the bar-supported overdenture may be preferred, because problems with aesthetics and alveolar ridge deficiencies can be solved more easily and the number of implants is reduced. Both, the "All-on-Four" technique and the "Procera implant bridge" are simple type of fixed prostheses, comparable to overdentures or complete dentures with regard to design and technology. They present a cost-effective alternative, with predictable aesthetics and optimum passive fit.


Anticonvulsant profile of caprylic acid, a main constituent of the medium-chain triglyceride (MCT) ketogenic diet, in mice.
The purpose of the present study was to evaluate the acute anticonvulsant effects of caprylic acid (CA), the main constituent of the medium-chain triglyceride ketogenic diet (MCT KD), in seizure tests typically used in screening for potential antiepileptic drugs in mice. Pharmacodynamic and pharmacokinetic interactions between CA and valproate (VPA) were also investigated. CA (p.o.) and VPA (i.p.) were administered 30 min before testing. Acute effects on motor coordination were assessed in the chimney test. Total plasma and brain concentrations of CA and VPA, when administered alone or in combination, were determined by high performance liquid chromatography. CA (10-30 mmol/kg) increased the threshold for i.v. pentylenetetrazole-induced myoclonic and clonic convulsions, but not tonic convulsions. CA (5-30 mmol/kg) increased the threshold for 6-Hz psychomotor seizures but was ineffective in the maximal electroshock seizure threshold test. CA (10-60 mmol/kg p.o.) impaired motor performance in the chimney test (TD(50) value, 58.4 mmol/kg). Increasing doses of CA (5-30 mmol/kg) produced proportional increases in plasma and brain exposure with constant brain/plasma partitioning. CA increased anticonvulsant potency of VPA in the maximal electroshock seizure and 6-Hz seizure tests. Co-administration of CA and VPA had no effect on brain and plasma concentrations of either compound. In summary, CA exerts acute anticonvulsant effects and potentiates the anticonvulsant effect of VPA at doses that result in plasma exposures comparable to those reported in epileptic patients on the MCT KD. Thus, this acute anticonvulsant property of CA may benefit and add to the overall clinical efficacy of the MCT KD.


Stress Induced Transcription Factors Transactivate the Herpes Simplex Virus 1 Infected Cell Protein 27 (ICP27) Transcriptional Enhancer.
Following acute infection, herpes simplex virus 1 (HSV-1) establishes lifelong latency in neurons, including sensory neurons within trigeminal ganglia. During latency, lytic cycle viral gene expression is silenced. However, stressful stimuli can trigger reactivation from latency. The viral tegument protein, VP-16, transactivates all immediate early (IE) promoters during productive infection. Conversely, cellular factors are expected to trigger viral gene expression during early stages of reactivation from latency and in non-neuronal cells that do not support high levels of productive infection. The glucocorticoid receptor (GR), synthetic corticosteroid dexamethasone, and certain stress-induced transcription factors cooperatively transactivate infected cell protein 0 (ICP0) and ICP4 promoters. Since ICP27 protein expression is required for productive infection, we hypothesized that the ICP27 promoter is transactivated by stress-induced transcription factors. New studies have demonstrated that ICP27 enhancer sequences were transactivated by GR and Krüppel-like factor 15 (KLF15). Mutation of a consensus Sp1 binding site within ICP27 enhancer sequences impaired transactivation by GR and KLF15. Chromatin immunoprecipitation studies have demonstrated that GR and KLF15 occupy ICP27 promoter sequences during productive infection. Cells transfected with an ICP27 enhancer fragment revealed the GR and KLF15 occupancy of ICP27 enhancer sequences required the intact Sp1 binding site. Notably, GR and KLF15 form a feed-forward transcription loop in response to stress, suggesting these cellular factors promote viral replication following stressful stimuli.


Angioimmunoblastic T-cell lymphoma: Novel recurrent mutations and prognostic biomarkers by cell-free DNA profiling.
Molecular and clinical stratification of patients with angioimmunoblastic T-cell lymphoma (AITL) is unsatisfactory, which hinders the development of personalized therapies. This study aimed to identify molecular biomarkers for AITL based on peripheral cell-free DNA (cfDNA) that could be used to predict prognosis and guide treatment non-invasively. A customized panel containing 46 genes was used to study pretreatment cfDNA and paired tumour tissues in 64 Chinese AITL patients from three clinical centres, and gene mutations in cfDNA and tumour tissue were assessed for concordance (34 paired samples). Then, the association of gene mutations and prognosis was analysed, and a functional enrichment analysis was performed. The sequencing results showed good consistency between cfDNA samples and paired tissue samples. KDM5A, STAT1, FANCM, ERBB4, PIK3R5 and NSD1 were identified as novel recurrent mutations. Mutations in FANCM or combinations of RHOA, KDM5A and FAT1 were associated with poor prognosis. Additionally, functional analysis revealed that RHOAG17 might serve as a predictive biomarker of PD-1 blockade respondence. Our findings confirmed the role of cfDNA as a liquid biopsy in AITL, and revealed novel molecular determinants that can stratify patients and guide treatment options.


The Effect of Light on the Synthesis of Mitochondrial Enzymes in Division-synchronized Euglena Cultures.
The development of the mitochondrial enzymes fumarase and succinate dehydrogenase has been followed in Euglena cultures division-synchronized by 14-hour light periods alternating with 12-hour dark periods. The activity of both enzymes was unaltered over the light phase, doubled in early dark phase, and thereafter remained constant over the rest of the cycle. The increase in enzyme activity in early dark phase probably represented de novo enzyme synthesis because it was prevented by the addition of cycloheximide at a concentration known to inhibit protein synthesis on Euglena cytoplasmic ribosomes.When division-synchronized cultures were darkened in early light phase, a doubling of both fumarase and succinate dehydrogenase activity resulted, showing that light was repressing enzyme synthesis. The addition of acetate did not have a similar effect to darkening cultures: enzyme activity being unaltered over the light phase of the cycle. Enzyme expression was also unaffected by the addition of 3-(3,4 dichlorophenyl)-1,1-dimethylurea, a potent inhibitor of photosynthetic carbon dioxide fixation. The addition of 6-methylpurine (an inhibitor of transcription) at the beginning of the light phase inhibited enzyme increase in early dark phase, but when added at a later stage of the light phase (hour 8), increase in enzyme activity in early dark phase was unaffected. We concluded that transcription for these enzymes occurs in early light phase but light exerts a post-transcriptional control so that enzyme synthesis does not result until cells enter the dark phase of the cell cycle.


Identifying and understanding barriers to sexually transmissible infection testing among young people.
To counter the disproportionate impact of sexually transmissible infections (STIs) among young people and encourage higher levels of STI testing, it is necessary to identify the factors that influence STI testing. A mixed-methods study incorporating a cross-sectional quantitative survey and qualitative analysis of individual interviews was conducted in England. Some 275 university students aged 17-25 years completed an online questionnaire. Interviews were conducted with a purposively selected sample of eight men and women. Multivariate analysis of quantitative data revealed that injunctive norms (i.e. a desire to comply with others' wishes for testing), descriptive norms (i.e. perceptions of others' behaviour) and shame related to STIs predicted past testing behaviour. Intention to undergo testing was predicted by greater perceived susceptibility, past testing, stronger injunctive norms and greater willingness to disclose sexual histories. Qualitative analysis of interview data confirmed the importance of perceived susceptibility, normative beliefs, stigma and shame, and perceived ease of testing. To increase STI testing among young people, there is a need to promote pro-testing norms, address low perceived susceptibility and make testing easier.


[Peroxidation components of sperm lipid membranes in male infertility].
We have studied the lipid peroxidation product (malondiadehyde-MDA) levels after thiobarbituric acid reaction, spectrophotometrically and by a high-performance liquid chromatography (HPLC) with UV detection in seminal plasma as well as in the cell fraction. Semen samples were obtained from healthy volunteers and infertile males. Ejaculates were previously classified into studied subgroups according to standard andrological criteria (sperm number, motility, morphology) and defined as: normozoospermia (K), azoospermia (Az), teratozoospermia (T), asthenoteratozoospermia (AT), oligoasthenoteratozoospermia (OAT) and idiopathic infertility (NIF). MDA is a good marker for lipid peroxidation. There were found elevated MDA concentrations (determined by HPLC) in seminal plasma of the all analysed pathological semen samples, especially in patients with OAT. The more pronounced differences between healthy controls and NIF patients were observed in intracellular compartment. The lipid peroxidation of rich in unsaturated fatty acids sperm membranes is considered to be one of the most important effects from ROS-induced cell damage what may lead to persistent infertility.


Calretinin immunoreactivity in cholinergic motor neurones, interneurones and vasomotor neurones in the guinea-pig small intestine.
Immunoreactivity for calretinin, a calcium-binding protein, was studied in neurones in the guinea-pig small intestine. 26 +/- 1% of myenteric neurones and 12 +/- 3% of submucous neurones were immunoreactive for calretinin. All calretinin-immunoreactive neurones were also immunoreactive for choline acetyltransferase and hence are likely to be cholinergic. In the myenteric plexus, two subtypes of Dogiel type-I calretinin-immunoreactive neurones could be distinguished from their projections and neurochemical coding. Some calretinin-immunoreactive myenteric neurones had short projections to the tertiary plexus, and hence are likely to be cholinergic motor neurones to the longitudinal muscle. Some of these cells were also immunoreactive for substance P. The remaining myenteric neurones, immunoreactive for calretinin, enkephalin, neurofilament protein triplet and substance P, are likely to be orad-projecting, cholinergic interneurones. Calretinin immunoreactivity was also found in cholinergic neurones in the submucosa, which project to the submucosal vasculature and mucosal glands, and which are likely to mediate vasodilation. Thus, calretinin immunoreactivity in the guinea-pig small intestine is confined to three functional classes of cholinergic neurones. It is possible, for the first time, to distinguish these classes of cells from other enteric neurones.


A novel locus for autosomal dominant nonsyndromic hearing loss, DFNA13, maps to chromosome 6p.
Nonsyndromic hearing loss (NSHL) is the most common type of hearing impairment in the elderly. Environmental and hereditary factors play an etiologic role, although the relative contribution of each is unknown. To date, 39 NSHL genes have been localized. Twelve produce autosomal dominant hearing loss, most frequently postlingual in onset and progressive in nature. We have ascertained a large, multigenerational family in which a gene for autosomal dominant NSHL is segregating. Affected individuals experience progressive hearing loss beginning in the 2d-4th decades, eventually making the use of amplification mandatory. A novel locus, DFNA13, was identified on chromosome 6p; the disease gene maps to a 4-cM interval flanked by D6S1663 and D6S1691, with a maximum two-point LOD score of 6.409 at D6S299.


[Inflammatory mechanism of depression and its new strategy for diagnosis and treatment].
Depression is a major class of mental illness; owing to its high prevalence, high disability rate and heavy disease burden, it has become a stern and formidable global health problem. It is generally believed that the etiology of depression is multifactorial, which is related to gender differences, chronic stress, dietary behavior and drug abuse. At present, the exact pathophysiological mechanism of depression still remains unclear, but researchers across the globe put forward various hypotheses to interpret the possible access to this disease, including monoamine neurotransmitter disturbance, hypothalamic-pituitary-adrenal (HPA) axis dysfunction, lack of neurotrophic factors and excessive pro-inflammatory cytokines. Based on the latest research evidence and the objective fact that traditional antidepressants may be ineffective in some particular patients, the "cytokine theory" tends to attract more and more attention recently. To date, researches on the role of cytokines in the pathogenesis of depression mainly focus on pro-inflammatory cytokines, especially categories including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). With the proceeding of researches from all over the world, a variety of novel molecules and mechanisms were postulated. This paper summarized a large amount of in vitro and in vivo research evidence, in order to review the current progress of the researches on pathophysiology of depression from the perspective of pro-inflammatory cytokines. Since the response rate of antidepressant therapy during present medical practice is unsatisfying, we suggest a new feasible diagnosis and treatment strategy, that is to distinguish the inflammatory status of patients with depression and take anti-inflammatory treatment into consideration. Totally, this novel strategy aims at modulating the conventional clinical protocol for treatment-resistant depressive patients and overcoming the limitation of insufficient antidepressant response possibly resulted from inflammation.


Treatment of restless legs syndrome.
Restless legs syndrome (RLS) is a common condition characterized by an urge to move the legs, accompanied by uncomfortable or unpleasant sensations. Symptoms predominantly occur at rest in the evening or at night, and they are alleviated by moving the affected extremity or by walking. Recent European epidemiological studies reported an overall prevalence of RLS up to 10%, with a female preponderance. The prevalence rates reported in south-eastern Europe are lower, as are those in Asiatic populations. Although the aetiopathogenesis of RLS is still unknown, the rapid and dramatic improvement of RLS with dopaminergic compounds suggests a dopaminergic system dysfunction as the basic mechanism. Extensive data are available for l-dopa and dopamine receptor agonists, especially for pramipexole and ropinirole. Pharmacological treatment should be limited to those patients who suffer from clinically relevant RLS with impaired sleep quality or quality of life. Treatment on demand is a clinical need in RLS cases that present intermittent symptoms.


Early changes in plasma pancreatic polypeptide, somatostatin, gastrin and motilin levels induced by H. contortus infection in lamb.
Plasma levels of pancreatic polypeptide (PP), somatostatin (GH-RIH), gastrin and motilin were measured during 6-7 h after oral infection with 25 000 infective (3rd stage) larvae of H. contortus in lambs or after intravenous injection of larvae or worm antigenic (Ag) extracts. A 3-fold increase in plasma gastrin was observed during the first 60 min after infection and GH-RIH increased significantly (P less than 0.01) 180 min later whereas both PP and motilin remained unchanged. An early (60 to 120 min) increase in GH-RIH and a late (5 to 7 h) increase in PP plasma levels were observed after both worm and larvae antigenic extracts whereas plasma motilin was unaffected. Plasma gastrin was significantly (P less than 0.01) increased during 3-4 h following the injection of worm but not of larvae antigenic extract. It was concluded that the immediate hypergastrinemia following H. contortus infection is not the consequence of a general immune response of the host and is probably related to the release of unknown substance(s) by the infective larvae into the abomasum or to mucosal inflammation due to a local immune response; in contrast, the increase in plasma GH-RIH levels appeared to be the result of antigenic reactions. The other hormonal changes observed after Ag injections may be the consequence rather than the reason of changes in abomasal secretory pattern.


Pongamol Inhibits Epithelial to Mesenchymal Transition Through Suppression of FAK/Akt-mTOR Signaling.
Cancer metastasis is the main cause of mortality in cancer patients. As lung cancer patients are mostly detected at metastatic stages, strategies that inhibit cancer metastasis may offer effective therapies. Activation of FAK and Akt/mTOR pathways promotes the highly metastatic phenotypes of epithelial to mesenchymal transition (EMT). We unraveled EMT inhibitory action of pongamol and the mechanism controlling cell dissemination in lung cancer cells. Cytotoxic and antiproliferative effects of pongamol were determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis and necrosis induction in response to pongamol treatment was observed and visualized by nuclei staining assay. Wound healing migration, invasion, and anchorage-dependent growth assay were conducted to evaluate metastatic behaviors. EMT protein expression and FAK pathway were detected by western blot analysis. Pongamol at 0-100 μM exhibited significant inhibition on migration, and invasion of cancer cells. Regarding anoikis resistance potential, the compound significantly inhibited survival and growth of cancer cells in an anchorage-independent manner, as indicated by the depletion of growing colonies in pongamol-pretreated cells. Protein level analysis further showed that pongamol exerted its anti-metastasis effect by inhibiting EMT, as indicated by a decrease of several mesenchymal proteins (N-cadherin, vimentin, Snail, and Slug). Regarding the up-stream mechanisms, we found that pongamol inhibited activation of FAK and Akt/mTOR signaling pathways. Pongamol exhibits potent anti-metastatic activity through suppressing key potentiating factors of cancer metastasis EMT and FAK.


[Synovial angiogenesis].
Synovial angiogenesis, the formation of new capillaries from pre-existent capillaries, is a constant feature of synovial inflammation. Strictly regulated, it normally disappears after recovery from the acute episode. However it may persist during chronic synovial inflammation and then participates in pannus development in RA. This is the result of biochemical events which have contributed to breakdown of the extracellular matrix and cartilage in association with activation or secretion into this micro-environment of angiogenic factors. Relations with immunocompetent cells (lymphocytes and monocytes) suggest that this final common pathway may be partially dependent upon stimulation by the antigen. The development of treatment aimed at inhibiting angiogenesis could offer additional therapeutic hope in rheumatoid arthritis.


Comparative evaluation of fragment reattachment protocols for the management of teeth with crown-root fractures.
A crown-root fracture is a fracture of both the crown and the root of a tooth. The International Association of Dental Traumatology (2020) guidelines recommended fragment reattachment and stabilization of loose fragments as an immediate management protocol for uncomplicated crown-root fractures. However, the lack of evidence and unpredictability make it a less popular treatment option. The aim of this study was to compare three protocols of fragment reattachment for the management of teeth with crown-root fractures. Eighty mandibular bovine incisors with similar dimensions and no structural deformities were selected and randomized into four groups: Group I (Control/sound teeth); Group II (no rehydration); Group III (rehydration in distilled water for 15 min) and Group IV (rehydration in a humidification chamber for 15 min). A fracture was simulated to extend from the labial side of the middle-third of the crown to the palatal side of the cervical-third of the root. Fragments were exposed to the environment under normal temperature and pressure. Fragments were later reattached as per the standard protocol following the rehydration as specified for each group. Samples were subjected to thermocycling, and the force required to fracture them was evaluated by using a universal testing machine. The highest mean force required to fracture was seen in Group IV (208.27 ± 75.99 N) followed by Group III (182.01 ± 90.13 N) and Group II (158.85 ± 68.04 N). These differences were statistically significant. Comparison of the mean difference of force required to fracture between pairs of groups revealed statistically significant mean differences only between the controls and each experimental group. The force required to fracture the reattached fragments in teeth with crown-root fractures was affected by rehydration of the fragments. The force was higher in fragments reattached after rehydration, and the highest force was required in the teeth that had been rehydrated in a humidification chamber.


[Towards establishing a platform of shared skills sets and competencies for public health doctors].
School physicians, public health medical officers and inspectors, and doctors who work in local public authorities and in the local services of the Ministry of Health all share a common public health skills set even if the activities and functions which they perform are quite different, and in some cases even very specific to their field of practice. After a cross-sectional review of their indispensable roles and tasks, we designed a referential system for shared competencies and have presented it to various active professionals. This tool serves as a starting point which has permitted us to tackle questions relating to the professionalisation, evaluation, and multi-disciplinary nature of these doctors. It also aims to contribute to the current reflection on the level of public health training necessary for all medical practitioners and doctors, but above and beyond that, more specifically for public health professionals.


Progressive display of very high resolution images using wavelets.
Digital or digitized biomedical images often have very high resolutions', which make them difficult or impossible to display on computer screens. Therefore, it is desirable to develop a multiresolution display method with which users can freely browse the contents of those high resolution images. In this paper, we present an improved wavelet-based progressive image display algorithm by stressing on the encoding and decoding process. The encoder, which dynamically determines levels of transform and partition of coefficients, is based on a modified Haar wavelet transform. The decoder retrieves the necessary data and reconstructs the requested region at a scale specified by the user. A prototype system, which enables virtually any size of images to be displayed progressively, has been implemented based on this algorithm. The system has low computational complexity for both encoding and decoding process.


Pain Intensity, Emotion Dysregulation, and Hazardous Drinking Among Adults With Chronic Pain.
Chronic pain and hazardous alcohol use (i.e., a pattern of alcohol consumption that increases risk for harmful consequences) are prevalent and frequently comorbid conditions that have been posited to interact in a bidirectional manner, leading to greater pain and heavier drinking. Despite evidence that emotion dysregulation (i.e., difficulty modulating emotional responses when experiencing negative emotions) is independently associated with both greater pain and greater alcohol consumption, we are not aware of any previous research examining relations between emotion dysregulation, pain intensity, and hazardous alcohol use among individuals with chronic pain. Participants included 125 past-month alcohol users with chronic musculoskeletal pain (38.4% female; mean age = 32.97 years; mean drinks/day = 1.62) who were recruited for an online survey study of pain and substance use. As expected, emotion dysregulation was positively associated with increased odds of hazardous alcohol use. We also observed a significant indirect association, such that higher levels of emotion dysregulation were associated with greater pain intensity, which in turn was associated with a greater likelihood of scoring above the Alcohol Use Disorders Identification Test cutoff for hazardous alcohol use. These findings suggest that emotion dysregulation may contribute to hazardous drinking among individuals with chronic pain, perhaps indirectly via pain amplification. Emotion dysregulation warrants consideration as a potential transdiagnostic vulnerability factor in comorbid chronic pain and hazardous drinking. Future prospective research is needed to examine causal pathways and establish temporal precedence.


Age-related change in human gastric mucosal energy metabolism.
Many investigators have reported a decrease in mucosal blood flow resulting in impairment of gastric mucosal energy metabolism in animal experiments. Recently, endoscopic studies using reflectance spectrophotometry and laser Doppler flowmetry have indicated that gastric mucosal blood flow in humans decreases with age. However, changes in energy metabolism in human gastric mucosa with age remains obscure. In this study, we measured adenine nucleotides in biopsy samples from human gastric mucosa, using high-performance liquid chromatography, and investigated changes in energy metabolism with age in subjects proven normal endoscopically. Energy charge (EC = (ATP + 1/2 ADP)/ATP + ADP + AMP) in the gastric antral and body mucosa showed decrease with age. When the subjects were divided into two groups, less than and more than 65 years old, the EC level was significantly lower in the latter than the former in both antral and body mucosa (0.65 +/- 0.06 versus 0.74 +/- 0.03 in the antrum, 0.73 +/- 0.04 versus 0.79 +/- 0.04 in the body) and significantly less in the antral mucosa than in body mucosa in both groups. The adenosine triphosphate (ATP) level in the older group showed a significant decrease (6.48 +/- 1.14 versus 9.63 +/- 1.92 in the antrum, 8.59 +/- 1.64 versus 10.60 +/- 2.13 in the body) compared with those less than 65 years old. In the antral mucosa of the older group the adenosine diphosphate (ADP) level was also significantly lower than that in the group less than 65. In conclusion, in the elderly, the energy metabolism in human gastric mucosa is impaired, and this may weaken their defensive mechanism.


What Motivates Medical Students to Engage in Volunteer Behavior During the COVID-19 Outbreak? A Large Cross-Sectional Survey.
After the COVID-19 outbreak, the health status of the general population has suffered a huge threat, and the health system has also encountered great challenges. As critical members of human capital in the health sector, medical students with specialized knowledge and skills have positively fought against the epidemic by providing volunteer services that boosted the resilience of the health system. Although volunteer behavior (VB) is associated with individual internal motivation, there is sparse evidence on this relationship among medical students, especially regarding potential mechanisms. Therefore, this study had two main objectives: (1) to examine the influence of prosocial motivation (PM) of medical students on their VB; and (2) to verify the chain-mediating role of calling and vocation (CV) as well as social responsibility (SR) in the relationship between PM and VB. Study I: a total of 2454 Chinese full-time medical students were invited to complete an online survey. Data analysis was performed using descriptive statistics, Pearson's correlation coefficient, and multiple linear regression analysis. The results demonstrated that PM significantly affected VB in medical students (β = 0.098, P < 0.001); CV as well as SR chain-mediated the relationship between PM and VB (β = 0.084, P < 0.001). PM promoted the formation of SR by positively evoking CV of medical students, further resulting in increased VB. Study II: A 28 person qualitative interview was conducted. Qualitative data are added to reduce the limitations of online questionnaires. At the same time, we can also critically study the VB of Chinese medical students during COVID-19. The results showed that there were various reasons for medical students to volunteer in the process of fighting against COVID-19, and the experience of volunteer service and the impact on their future life were different. Lastly, the current findings suggest that fostering volunteerism among medical students requires the joint effort of the government, non-profit organizations, and medical colleges.


Dietary protein-induced proctocolitis in childhood.
Cow's milk protein-induced proctocolitis presents with overt rectal bleeding in otherwise healthy infants and is characterized by an eosinophilic infiltrate of the left colonic mucosa. Although it is the most common cause of proctocolitis in infancy, dietary protein-induced proctocolitis had hardly ever been reported in childhood so far. We hereby report 16 otherwise healthy children aged 2-14 yr, who presented over a 6-yr period with persistent or recurrent rectal bleeding related to a mild form of left-sided colitis characterized by a prominent eosinophilic infiltration, focal lymphoid follicle hyperplasia, and a prompt clinical and histological response to a cow's milk-free diet. No patient had a history of food-induced proctocolitis during infancy, and most patients did not show an IgE-mediated response to cow's milk protein. Half of the patients did have other gastrointestinal symptoms, but no systemic symptoms were present and other causes of colitis were excluded by appropriate investigation. Tolerance to cow's milk protein developed in half of the patients within a year. Dietary protein-induced proctocolitis is a relatively common cause of overt rectal bleeding in childhood, and its features are remarkably similar to those of dietary protein-induced proctocolitis of infancy.


The Experiences of Nurses of Infectious and Non- Infectious Wards of Caring COVID-19 Patients in a Big Hospital in Iran: A Qualitative Study.
Nurses play a very important role in caring for patients with coronavirus disease-19 (COVID-19). They are on the frontline fighting COVID-19. The objective was to explore the experiences of nurses in the surgical and infectious wards about caring for patients with COVID-19 in a large and tertiary care hospital in Iran. This was a qualitative study. Semi-structured qualitative interviews were conducted with 18 nurses in the Imam Reza Hospital Complex from April to May 2020, Mashhad, Iran. Data analysis was performed using the method proposed by Lundman and Granheim. The Maxqda10 software was used. The experiences were summarized into three categories: (1) experiencing new feelings and relationships with colleagues and patients, (2) viewpoints about managers' performance, and (3) concern about getting infected with COVID-19. Findings reflected similar experiences on personal protective equipment between nurses in the surgical and infectious wards. Experiencing new feelings and relationships with colleagues and patients and concern about getting infected and spreading the COVID-19 were mostly expressed by infectious nurses and surgical nurses, respectively. This research results provide evidence of the experiences of infectious and non-infectious disease nurses who are currently caring for COVID-19 patients. Due to some differences between the experiences of these two groups in COVID-19, it is suggested to pay more attention to the needs and required skills in the staff mix during a crisis.


Voltage-clamp studies on uterine smooth muscle.
These studies have developed and tested an experimental approach to the study of membrane ionic conductance mechanisms in strips of uterine smooth muscle. The experimental and theoretical basis for applying the double sucrose-gap technique is described along with the limitations of this system. Nonpropagating membrane action potentials were produced in response to depolarizing current pulses under current-clamp conditions. The stepwise change of membrane potential under voltage-clamp conditions resulted in a family of ionic currents with voltage- and time-dependent characteristics. In sodium-free solution the peak transient current decreased and its equilibrium potential shifted along the voltage axis toward a more negative internal potential. These studies indicate a sodium-dependent, regenerative excitation mechanism.


[Clinical study on treating insulin resistance and promoting ovulation in polycystic ovary syndrome].
To investigate the effects of metformin and clomiphene on infertility caused by polycystic ovary syndrome (PCOS) with insulin-resistance (IR) and to observe the effects of metformin on PCOS with pseudoacanthosis nigricans (AN) and IR. Seventy infertility patients caused by PCOS with IR were randomly divided into three groups : patients in group Aa (n = 20) took metformin 500 mg only, three times daily for 3 months; patients in group Ab (n = 20) took clomiphene 50 mg only, once daily from the 5th day of menstrual cycle or withdrawal bleeding for 5 days and 3 cycles, and patients in group Ac (n = 30) were treated by metformin and clomiphene for 3 cycles, with the same dosages as groups Aa and Ab. Thirty patients who suffered from PCOS with AN and IR were served as group B, They took metformin only, the same as group Aa. The following indexes were measured before and after three months or cycles of treatment in all the patients: body height, weight, waistline, hipline, body mass index (BMI), waist hip ratio (WHR), fasting insulin (FINS), fasting blood-glucose (FBG), total cholesterol (TC), triglyceride (TG), and sex hormones [follicle-stimulating hormone (FSH), luteotropic hormone (LH), prolactin (PRL), estradiol (E(2)), progestin (P), testosterone (T)]. The pregnant rate was 15% (group Aa), 20% (group Ab), and 57% (group Ac) respectively. It was significantly higher in group Ac than in groups Aa and Ab, (P < 0.01), while there was no significant difference between the latter two groups (P > 0.05). In group Ac the pretreatment levels of FINS, BMI, T, TG, and TC were (49.7 +/- 6.4) mU/L, 29.4 +/- 2.2, (6.4 +/- 2.2) nmol/L, (4.1 +/- 1.0) mmol/L, (6.3 +/- 0.5) mmol/L, and posttreatment levels were (27.7 +/- 1.8) mU/L, 23.6 +/- 5.2, (3.8 +/- 2.0) nmol/L, (2.2 +/- 0.7) mmol/L, (4.6 +/- 0.5) mmol/L. In group Aa pretreatment levels of FINS, BMI, T, TG, and TC were (50.0 +/- 8.2) mU/L, 28.7 +/- 1.2, (6.4 +/- 2.0) nmol/L, (4.3 +/- 1.2) mmol/L, (6.6 +/- 0.3) mmol/L, and posttreatment levels were (29.9 +/- 8.2) mU/L, 22.4 +/- 9.3, (4.3 +/- 0.9) nmol/L, (2.3 +/- 0.3) mmol/L, (4.8 +/- 0.6) mmol/L. In group B pretreatment levels of FINS, BMI, T, TG, and TC were (51.0 +/- 8.1) mU/L, 29.8 +/- 3.1, (6.3 +/- 3.5) nmol/L, (4.5 +/- 1.2) mmol/L, (6.8 +/- 0.2) mmol/L, and posttreatment levels were (28.5 +/- 2.8) mU/L, 23.4 +/- 6.1, (3.0 +/- 0.9) nmol/L, (2.3 +/- 0.9) mmol/L, (5.0 +/- 0.6) mmol/L. In groups Ac, Aa and B, the IR condition was obviously improved and posttreatment serum levels of T, TG, TC, FINS and BMI were significantly lower than those of pretreatment (all P < 0.01). In group Ab pretreatment levels of FINS, BMI, T, TG, and TC were (48.8 +/- 7.4) mU/L, 27.3 +/- 2.8, (6.0 +/- 2.0) nmol/L, (3.9 +/- 1.4) mmol/L, (6.4 +/- 0.6) mmol/L, and posttreatment levels were (42.9 +/- 7.0) mU/L, 27.5 +/- 3.1, (4.0 +/- 2.4) nmol/L, (3.9 +/- 0.3) mmol/L, (5.9 +/- 0.3) mmol/L, (all P > 0.05). Among patients in group B, 90% (27/30) menstrual condition and ovulation function were improved and AN was reduced in different degree after three months' treatment. Metformin can increase the sensitivity of PCOS to clomiphene and improve ovulation function of clomiphene. Metformin plus clomiphene is an effective way of treating infertility caused by PCOS with IR.


Cost effective moulded seating for the handicapped child.
For many severely handicapped children requiring external trunk support there is probably no better solution than to provide custom moulded seating. This will improve the patient's posture, reduce the occurrence of pressure sores and facilitate such activities as feeding. However, if large numbers of patients are to be supplied with this type of equipment, it is important that it should be manufactured at the lowest cost compatible with an acceptable quality. These manufacturing problems have been studied in considerable detail and a production method using vacuum consolidation casting together with a modified vacuum forming process has been developed. This has made it possible to produce custom moulded seating efficiently with the minimum of capital equipment. Much attention has been paid to the final appearance of the article and this has been enhanced by the use of commercially available items for the supporting structure and for the finishing of edges, etc. It is suggested that other orthoses could be redesigned for production using an approach similar to that described in this paper.


Stereospecificity of leukotriene B4 and structure-function relationships for chemotaxis of human neutrophils.
The chemotactic activity of leukotriene B4 (5S, 12R Dihydroxy 6, 14 cis, 8, 10 trans eicosatetraenoic acid) (LTB4) was examined by using a sensitive Boyden-chamber assay. The activity of LTB4 was compared to other biosynthetic stereoisomers: 5S, 12R Dihydroxy 6, 8, 10 trans 14 cis eicosatetraenoic acid (6-trans LTB4); 5S, 12S Dihydroxy 6, 8, 10 trans 14 cis eicosatetraenoic acid (12-epi-6-trans LTB4), 5S, 12S DiHETE; the metabolic product 20-Hydroxy LTB4 (20-OH LTB4); methylated LTB4 (Methyl-LTB4), and the related monoHETE 5-HETE and 12-HETE. The compounds were purified by several steps of reverse phase and straight phase HPLC. The LTB4 exhibits measurable chemotactic activity at 10(-9) M with maximal activity at 10(-7) M and an ED50 of 10(-8) M. The LTB4 isomers and monoHETE were less chemotactic than previously reported. The monoHETE (5-HETE and 12-HETE), the isomer 12-epi-6-trans LTB4, and 5S, 12S DiHETE fail to attract neutrophils at levels between 10(-6) and 10(-5) M. If these compounds are chemotactic, then activity is at least four orders of magnitude less than that of LTB4. The isomer 6-trans LTB4 at 10(-6) to 10(-5) M induced chemotaxis with an extrapolated ED50 value of 10(-5) M, indicating that a trans for cis change in configuration at position 6 reduces the chemotactic activity of LTB4 by 1000-fold. Conversely, the metabolic product 20-OH LTB4 is at least as active as the native compound LTB4. Methylation of the carboxyl group of LTB4 reduces its chemotactic activity by two orders of magnitude. These results indicate a high degree of stereospecificity for the LTB4 receptor with strict dependence on hydroxyl group, and triene configuration and considerable dependence on the carboxyl group. Modification at the aliphatic omega end of the LTB4 molecule has a minimal effect on function, suggesting that the hydrophobicity of this portion of the molecule is not important for optimal activity. Furthermore, we propose that metabolic products of LTB4 may be of greater importance than LTB4 as physiologic inflammatory mediators in vivo.


[Postoperative, appositional ossifications after lumbar laminectomy].
Post-laminectomy segmental hypermobility as well as appositional ossification were suggested by many authors to contribute to the unsatisfactory long-term results of laminectomy. The aim of this study was to find out whether segmental instability, among other factors, influences the degree of appositional ossification following laminectomy. 55 out of 72 patients operated upon by laminectomy or hemilaminectomy for degenerative lumbar spinal stenosis were examined by radiography after an average follow-up period of 5.2 years. Appositional ossification at the site of surgery was evaluated in relation to lumbar instability, the number of segments undergoing laminectomy, and whether simultaneous fusion was done. Instability was determined by measuring angulation and translation using lateral flexion and extension views of the lumbar spine, whereas new-bone formation was best evaluated on antero-posterior radiographs. 94% of the patients had appositional ossification at the site of laminectomy. Patients undergoing simultaneous fusion with laminectomy had a significantly lower amount of appositional ossification compared to patients undergoing laminectomy without segmental fusion. Radiographically measured segmental instability, the number of segments undergoing laminectomy, age, and sex of the patients did not influence the extent of ossification. Postoperative appositional ossification at the posterior site of resection are seen regularly following laminectomy. The extent of appositional ossification does correlate with lumbar fusions, but does not correlate with the extent of radiographically measured lumbar instability, the number of segments undergoing laminectomy, or the age and sex of the patients. Simultaneous lumbar fusion with laminectomy is proved to be associated with less appositional ossification. Therefore lumbar fusion should be considered when planning surgery for spinal stenosis.


The Use of Submental Island Flap for Total Lower Lip Reconstruction: A Case Report.
Total lower lip reconstruction was performed in a 72-year-old man following a squamous cell carcinoma resection. To obtain an optimal functional result and to avoid any additional facial scarring, a submental island flap was used in a one-stage procedure. After 2.5 years of follow-up, the patient is very satisfied with the shape and function of the lower lip.


Bromine chloride as an oxidant to improve elemental mercury removal from coal-fired flue gas.
The equilibria and kinetics of the reaction between bromine (Br(2)) and chlorine (Cl(2)) to form bromine chloride (BrCl) at various temperatures were determined. BrCl was employed to oxidize elemental mercury (Hg(0)) under simulated flue gas conditions. The removal of Hg(0) from the gas phase by a homogeneous gas-phase oxidation reaction and the heterogeneous reactions involving flyash were investigated. The second-order gas phase rate constant was determined to be 2.3(+/-0.2) x 10(-17) cm(3).molecules(-1).s(-1) at 373K. The reaction of Hg(0)/BrCl was significantly accelerated in the presence of flyash, and the estimated Hg(0) removal efficiency in the presence of 0.6 ppmv BrCl and 20 g/m(3) flyash was up to 90%. Unexpectedly, the major product was found to be HgCl(2), rather than HgBr(2), indicating that bromine in part acted as the accelerant in Hg(0) oxidation in BrCl/Br(2)/Cl(2) system by facilitating the formation of intermediates. As a result, bromine consumption is much less than if only bromine gas is utilized alone. These results were helpful not only for understanding the mechanism of Hg(0) removal in coal-fired flue gas but also in any atmosphere in which bromine and chlorine species coexist.


A telephone-linked computer system for home enteral nutrition.
We studied the effect of telephone-linked computer (TLC) communication in patients being treated with home enteral nutrition. A total of 290 patients were enrolled in the study which compared two groups of patients who were recruited at different times (control: 193, TLC: 97). At baseline there were no significant differences in characteristics or clinical practice between the two groups. Over a three-month period, 823 automatic telephone calls were dialled out to the TLC patients and in 787 of the calls (96%) there were complete responses to all questions. A total of 205 alert messages were generated for the 823 calls. Less than 10% were false alerts. All health outcome measures, the EQ-5D and three components of the SF-36 improved slightly with time in both groups, but there was no significant difference between the groups. The patients' body mass index increased slightly in both groups, but the change was not significant. Home enteral nutrition prevented weight loss and improved some components of the QOL scores. The TLC system detected a high number of abnormal nutritional symptoms.


Adult height in girls with Turner syndrome treated from before 6 years of age with a fixed per kilogram GH dose.
To evaluate adult height (AH) in 25 girls with Turner syndrome (TS) who were treated from before 6 years of age for 10.0 ± 1.7 years with a fixed GH dose of 0.33 mg/kg per week. After a 6-month pretreatment assessment all patients were measured 6-monthly under therapy to assess height SDS (H-SDS) and height velocity (HV) until AH achievement. Following initial acceleration, HV declined after the first 4 years of therapy. At the end of the sixth year of therapy, H-SDS gain was 1.9 ± 1.1. Thereafter, H-SDS gain from baseline decreased, becoming 0.9 ± 0.9 SDS at AH achievement. Bone maturation velocity did not significantly change throughout the prepubertal period. According to Lyon standards for TS, mean AH SDS was significantly higher than pretreatment H-SDS (P<0.0001), with a mean H-SDS change of 0.9 ± 0.9. However, the prevalence of patients with AH <-2 SDS (according to Sempé standards) was close to those recorded at the start of therapy (16/25 vs 18/25). No significant differences in terms of AH were found between patients with either X monosomy or X-chromosomal abnormalities and between girls with either spontaneous or induced puberty. We infer that the therapeutic regimen adopted in this prospective study is sufficient to induce a significant growth acceleration during the first year, but the response waned after 6 years of treatment.


Efficient nonarterialized mouse liver transplantation using 3-dimensional-printed instruments.
Because of the wide availability of genetically modified animals, mouse orthotopic liver transplantation is often preferred over rat liver transplantation. We present a simplified mouse liver transplantation technique and compare transplantation outcomes with versus without hepatic artery anastomosis. Instruments for liver implantation were designed and printed with a 3-dimensional (3D) printer. The suprahepatic vena cava anastomosis was performed with a 10-0 running suture. The vena porta and infrahepatic vena cava were joined on extraluminal cuffs, using the 3D-printed device for spatial alignment and stabilization. The hepatic artery was reconstructed in half of the recipients using intraluminal stents. Liver function tests (3, 7, and 28 days) and histology (7 and 28 days) were assessed after transplantation. We performed 22 consecutive syngeneic C57BL/6 mouse orthotopic liver transplantations. The median portal clamping time was 12.5 ± 1.5 minutes. The survival rate at 4 weeks was 100% for both arterialized and nonarterialized recipients (n = 7, 4 recipients of each group being killed for early histology at day 7). Liver function tests at 3, 7, and 28 days were similar between arterialized versus nonarterialized groups. Liver parenchyma demonstrated only irrelevant abnormalities in both groups. The proposed device allows for a shorter clamping time compared with the published literature. Using this technique, the artery does not need to be anastomosed, with no impact on graft and recipient outcomes. The device is available for 3D printing. Liver Transplantation 22 1688-1696 2016 AASLD.


Continuously active disinfectant inactivates severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and human coronavirus 229E two days after the disinfectant was applied and following wear exposures.
The surface environment in rooms of coronavirus disease 2019 (COVID-19) patients may be persistently contaminated despite disinfection. A continuously active disinfectant demonstrated excellent sustained antiviral activity following a 48-hour period of wear and abrasion exposures with reinoculations. Reductions of >4-log10 were achieved within a 1-minute contact time for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and the human coronavirus, 229E.


Deprescribing Inappropriate Proton Pump Inhibitors in a Family Medicine Residency Practice Office.
Proton pump inhibitors (PPIs) are often prescribed beyond their medically-approved duration of use. Long-term PPI use has been linked with numerous adverse effects and contributes to polypharmacy. This study sought to understand the effect of evidence-based education to resident and faculty physicians on deprescribing inappropriate PPIs. We hypothesized that this educational intervention would result in fewer inappropriate PPI prescriptions. We performed a chart review on all adult patients in a family medicine residency program practice, identifying those inappropriately taking PPIs. All physicians in the practice participated in an educational intervention regarding deprescribing inappropriate PPIs and were given frequent reminders to continue their deprescribing efforts. We reviewed charts at the end of the study to identify patients with successful deprescribing attempts. Of the 187 patients prescribed inappropriate PPIs in the study, 100 remained on PPIs at the end of the study (46.6% success rate). There was a significant decrease in the number of patients inappropriately prescribed PPIs by each physician over the course of the study, from a mean of 17.0 (beginning) to 9.1 (end). Physician education with reminders is an effective means of reducing the number of inappropriate PPIs prescribed in a family medicine residency practice. Future studies could investigate the effectiveness of educational interventions with other medication classes that are often prescribed inappropriately.


Association between ADAM33 polymorphisms and susceptibility with adult and childhood asthma among Jordanians.
Disintegrin and metalloprotease 33 (ADAM33) have been associated with childhood and adult asthma in many populations. ADAM33 mutations might predispose to altered lung function in early infancy. In this study, we investigated the association between single-nucleotide polymorphisms in ADAM33 and the incidence of adult and childhood asthma among Jordanians. One hundred seven pediatric asthmatic patients, 115 healthy pediatric patient controls, 160 adult asthmatic patients, and 110 healthy adults were enrolled in this study. ADAM33 polymorphisms were genotyped using the polymerase chain reaction/restriction fragment length polymorphism method. A strong association between the V4 genotype and incidence of childhood asthma was found. In the single-locus analyses of asthma risk, V4 C/G single nucleotide polymorphism (SNP) showed a trend toward significance with p=0.07. Interestingly, the CC homozygous mutant genotype frequency was significantly higher in asthmatic subjects (15.9%) than in control subjects (2.6%), resulting in an odds ratio of 7.05. In adult cases, S2, the F+1 and Q-1 genotype showed a significant association (p≤0.05) with the incidence of asthma. Two haplotypes also exhibited a significant association with asthma (p≤0.05). In conclusion, the findings of this study confirm the already reported association between V4 SNP and the incidence of childhood asthma as well as between S2, F+1, and Q-1 SNPs and the incidence of adult asthma in several populations.


In vivo photoprotection mechanisms observed from leaf spectral absorbance changes showing VIS-NIR slow-induced conformational pigment bed changes.
Regulated heat dissipation under excessive light comprises a complexity of mechanisms, whereby the supramolecular light-harvesting pigment-protein complex (LHC) shifts state from light harvesting towards heat dissipation, quenching the excess of photo-induced excitation energy in a non-photochemical way. Based on whole-leaf spectroscopy measuring upward and downward spectral radiance fluxes, we studied spectrally contiguous (hyperspectral) transient time series of absorbance A(λ,t) and passively induced chlorophyll fluorescence F(λ,t) dynamics of intact leaves in the visible and near-infrared wavelengths (VIS-NIR, 400-800 nm) after sudden strong natural-like illumination exposure. Besides light avoidance mechanism, we observed on absorbance signatures, calculated from simultaneous reflectance R(λ,t) and transmittance T(λ,t) measurements as A(λ,t) = 1 - R(λ,t) - T(λ,t), major dynamic events with specific onsets and kinetical behaviour. A consistent well-known fast carotenoid absorbance feature (500-570 nm) appears within the first seconds to minutes, seen from both the reflected (backscattered) and transmitted (forward scattered) radiance differences. Simultaneous fast Chl features are observed, either as an increased or decreased scattering behaviour during quick light adjustment consistent with re-organizations of the membrane. The carotenoid absorbance feature shows up simultaneously with a major F decrease and corresponds to the xanthophyll conversion, as quick response to the proton gradient build-up. After xanthophyll conversion (t = 3 min), a kinetically slower but major and smooth absorbance increase was occasionally observed from the transmitted radiance measurements as wide peaks in the green (~ 550 nm) and the near-infrared (~ 750 nm) wavelengths, involving no further F quenching. Surprisingly, in relation to the response to high light, this broad and consistent VIS-NIR feature indicates a slowly induced absorbance increase with a sigmoid kinetical behaviour. In analogy to sub-leaf-level observations, we suggest that this mechanism can be explained by a structure-induced low-energy-shifted energy redistribution involving both Car and Chl. These findings might pave the way towards a further non-invasive spectral investigation of antenna conformations and their relations with energy quenching at the intact leaf level, which is, in combination with F measurements, of a high importance for assessing plant photosynthesis in vivo and in addition from remote observations.


Antimicrobial Lemongrass Essential Oil-Copper Ferrite Cellulose Acetate Nanocapsules.
Cellulose acetate (CA) nanoparticles were combined with two antimicrobial agents, namely lemongrass (LG) essential oil and Cu-ferrite nanoparticles. The preparation method of CA nanocapsules (NCs), with the two antimicrobial agents, was based on the nanoprecipitation method using the solvent/anti-solvent technique. Several physical and chemical analyses were performed to characterize the resulting NCs and to study their formation mechanism. The size of the combined antimicrobial NCs was found to be ca. 220 nm. The presence of Cu-ferrites enhanced the attachment of LG essential oil into the CA matrix. The magnetic properties of the combined construct were weak, due to the shielding of Cu-ferrites from the polymeric matrix, making them available for drug delivery applications where spontaneous magnetization effects should be avoided. The antimicrobial properties of the NCs were significantly enhanced with respect to CA/LG only. This work opens novel routes for the development of organic/inorganic nanoparticles with exceptional antimicrobial activities.


Consonant Age-of-Acquisition Effects in Nonword Repetition Are Not Articulatory in Nature.
Most research examining long-term-memory effects on nonword repetition (NWR) has focused on lexical-level variables. Phoneme-level variables have received little attention, although there are reasons to expect significant sublexical effects in NWR. To further understand the underlying processes of NWR, this study examined effects of sublexical long-term phonological knowledge by testing whether performance differs when the stimuli comprise consonants acquired later versus earlier in speech development. Thirty (Experiment 1) and 20 (Experiment 2) college students completed tasks that investigated whether an experimental phoneme-level variable (consonant age of acquisition) similarly affects NWR and lexical-access tasks designed to vary in articulatory, auditory-perceptual, and phonological short-term-memory demands. The lexical-access tasks were performed in silence or with concurrent articulation to explore whether consonant age-of-acquisition effects arise before or after articulatory planning. NWR accuracy decreased on items comprising later- versus earlier-acquired phonemes. Similar consonant age-of-acquisition effects were observed in accuracy measures of nonword reading and lexical decision performed in silence or with concurrent articulation. Results indicate that NWR performance is sensitive to phoneme-level phonological knowledge in long-term memory. NWR, accordingly, should not be regarded as a diagnostic tool for pure impairment of phonological short-term memory. https://doi.org/10.23641/asha.5435137.