Multimodal pain management and the future of a personalized medicine approach to pain.
In the soon-to-be-released clinical practice guidelines from the American Pain Society, multimodal analgesia is recommended for pain management after all surgical procedures. Multimodal analgesia is a surgery-specific population-based approach to optimize pain relief by treating pain through multiple mechanisms along multiple sites of the nociceptive pathway. The reliance on multiple medications and therapies inherent to the multimodal approach also may address individual patient differences in analgesic pharmacogenetics (ie, the influence of allelic differences in single genes and the associated variability in specific medication responses). Perioperative nurses may see a shift from surgery-specific population-based multimodal analgesic protocols to a personalized medicine approach as knowledge of the genetic influences of analgesic metabolism and pain sensitivity is translated into clinical practice. Personalized medicine is proposed as an individualized pain management treatment plan that eventually may be based on each patient's genetic coding for metabolism of analgesics and pain sensitivity.


Alpha-aminothiazole-gamma-aminobutanoic amides as potent, small molecule CCR2 receptor antagonists.
A series of racemic and homochiral alpha-aminothiazole-gamma-aminobutyroamides that display high affinities for human and murine CCR2 and functional antagonism by inhibition of monocyte recruitment are described. A representative example is (2S)-2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-[3-methyl-5-(trifluoromethyl)benzyl]-4-(4-phenylpiperidin-1-yl)butanamide, which shows 5 nM affinity for human monocytes and CHO cells expressing the human CCR2b receptor. It also inhibited MCP-1 initiated chemotaxis of human monocytes with an IC50 of 0.69 nM.


Effect of fatty acids on melanogenesis and tumor cell growth in melanoma cells.
Fatty acids have various physiological effects on melanoma. For example, palmitic acid (PA) increases melanin levels; linoleic acid and DHA decrease melanin levels; and DHA suppresses tumor growth. In this study, we focused on the relationship between the structure of fatty acids and their physiological effects in melanoma to examine the likely mechanisms of action. We showed that saturated fatty acids and PUFAs display opposing effects on melanin content in melanoma cells. Likewise, PA and EPA have opposing effects in terms of actin polymerization. Our findings suggest that PA and EPA change melanin content in melanoma to alter melanosome trafficking by modulating actin polymerization. Here, we also examined the mechanism of the anti-tumor effect of DHA. We found that DHA interacts with receptor for activated C kinase 1 and represses melanoma cell proliferation by suppressing protein kinase C signaling. Our results suggest a new mechanism to explain the physiological effects of fatty acids.


Pancreatic echinococcosis in a 5-year-old girl.
Pancreatic echinococcosis accounts for 0.2-0.6% of cases, with the pediatric population being at a higher risk. Most commonly, pancreatic lesions occur in the head of the pancreas (50-58%); and in the body and tail in 24-34% and 19% of cases, respectively. Given the potential complications, surgery is usually performed. Albendazole is recommended before and after the surgery due to the risks for rupture and dissemination of protoscolices. Here we describe the case of a 5-year-old girl with progressive abdominalpain and cystic lesion in the pancreas compatible with echinococcosis in the ultrasound. The computed tomography showed bile duct compression. Indirect hemagglutination was negative. She had elevated total bilirubin, with a clear predominance of direct bilirubin, and high liver enzymes. Exploratory laparotomy, cholecystectomy, and unroofing of the cyst were performed. The patient had a favorable course and continued with albendazole for 3 months after the surgery.


Identification of two novel Drosophila melanogaster histamine-gated chloride channel subunits expressed in the eye.
Histamine has been shown to play a role in arthropod vision; it is the major neurotransmitter of arthropod photoreceptors. Histamine-gated chloride channels have been identified in insect optic lobes. We report the first isolation of cDNA clones encoding histamine-gated chloride channel subunits from the fruit fly Drosophila melanogaster. The encoded proteins, HisCl1 and HisCl2, share 60% amino acid identity with each other. The closest structural homologue is the human glycine alpha3 receptor, which shares 45 and 43% amino acid identity respectively. Northern hybridization analysis suggested that hisCl1 and hisCl2 mRNAs are predominantly expressed in the insect eye. Oocytes injected with in vitro transcribed RNA, encoding either HisCl1 or HisCl2, produced substantial chloride currents in response to histamine but not in response to GABA, glycine, and glutamate. The histamine sensitivity was similar to that observed in insect laminar neurons. Histamine-activated currents were not blocked by picrotoxinin, fipronil, strychnine, or the H2 antagonist cimetidine. Co-injection of both hisCl1 and hisCl2 RNAs resulted in expression of a histamine-gated chloride channel with increased sensitivity to histamine, demonstrating coassembly of the subunits. The insecticide ivermectin reversibly activated homomeric HisCl1 channels and, more potently, HisCl1 and HisCl2 heteromeric channels.


Personality and Neural Correlates of Mentalizing Ability.
Theory of mind, or mentalizing, defined as the ability to reason about another's mental states, is a crucial psychological function that is disrupted in some forms of psychopathology, but little is known about how individual differences in this ability relate to personality or brain function. One previous study linked mentalizing ability to individual differences in the personality trait Agreeableness. Agreeableness encompasses two major subdimensions: Compassion reflects tendencies toward empathy, prosocial behavior, and interpersonal concern, whereas Politeness captures tendencies to suppress aggressive and exploitative impulses. We hypothesized that Compassion but not Politeness would be associated with better mentalizing ability. This hypothesis was confirmed in Study 1 (N = 329) using a theory of mind task that required reasoning about the beliefs of fictional characters. Post hoc analyses indicated that the honesty facet of Agreeableness was negatively associated with mentalizing. In Study 2 (N = 217), we examined whether individual differences in mentalizing and related traits were associated with patterns of resting-state functional connectivity in the brain. Performance on the theory of mind task was significantly associated with patterns of connectivity between the dorsal medial and core subsystems of the default network, consistent with evidence implicating these regions in mentalization.


The Cytoskeleton of the Retinal Pigment Epithelium: from Normal Aging to Age-Related Macular Degeneration.
The retinal pigment epithelium (RPE) is a unique epithelium, with major roles which are essential in the visual cycle and homeostasis of the outer retina. The RPE is a monolayer of polygonal and pigmented cells strategically placed between the neuroretina and Bruch membrane, adjacent to the fenestrated capillaries of the choriocapillaris. It shows strong apical (towards photoreceptors) to basal/basolateral (towards Bruch membrane) polarization. Multiple functions are bound to a complex structure of highly organized and polarized intracellular components: the cytoskeleton. A strong connection between the intracellular cytoskeleton and extracellular matrix is indispensable to maintaining the function of the RPE and thus, the photoreceptors. Impairments of these intracellular structures and the regular architecture they maintain often result in a disrupted cytoskeleton, which can be found in many retinal diseases, including age-related macular degeneration (AMD). This review article will give an overview of current knowledge on the molecules and proteins involved in cytoskeleton formation in cells, including RPE and how the cytoskeleton is affected under stress conditions-especially in AMD.


Monocyte dysfunction in Sydenham's chorea patients.
Until now, there are no conclusive data about the mechanisms involved in motor symptoms of Sydenham's chorea (SC). Taking into account the autoreactive antibody-mediated hypothesis of SC pathogenesis, the SC may be associated with uncontrolled immune mechanisms. Besides the antibody hypothesis, the innate immune system has been underappreciated. Hence, we evaluated the activation state of monocytes, cells that are precursors of macrophages, to characterize the inflammation profile of patients. We assessed the surface molecules CD80, CD86, and human leukocyte antigen DR expression in patients with SC by flow cytometry analysis. Our results showed a decreased CD14(+) (monocyte) frequency, with concomitant increased CD14(-) frequency inside monocyte population. Although monocyte population showed a decreased human leukocyte antigen DR and CD86 frequencies, the CD14(-) population showed an increased frequency of CD80(+) monocyte from SC compared with controls. These data suggest that monocytes showed a reduced costimulatory potential in SC.


Effects of an 8-Week In-Season Elastic Band Training Program on Explosive Muscle Performance, Change of Direction, and Repeated Changes of Direction in the Lower Limbs of Junior Male Handball Players.
Aloui, G, Hammami, M, Fathloun, M, Hermassi, S, Gaamouri, N, Shephard, RJ, and Chelly, MS. Effects of an 8-week in-season elastic band training program on explosive muscle performance, change of direction, and repeated changes of direction in the lower limbs of junior male handball players. J Strength Cond Res 33(7): 1804-1815, 2019-The aim of this study was to examine the effects of incorporating 8 weeks of biweekly lower-limb elastic band training (knee and hip extension) into the in-season regimen of junior handball players. Study participants (30 men, aged 18.7 ± 0.8 years, body mass 81.1 ± 15.4 kg, height 1.82 ± 0.06 m, body fat: 15.5 ± 5.2%) were randomly assigned between control and experimental groups. Measures obtained before and after intervention included a cycle ergometer force-velocity test, force platform determinations of squat and countermovement jump characteristics, sprint times (5 and 30 m), repeated change-of-direction (RCOD) and change-of-direction (T-half, COD) tests, 1 repetition maximum (RM) half back squat, and anthropometric estimates of limb muscle volumes. Small to trivial improvements of experimental subjects relative to control subjects included peak power (p < 0.001), 1RM strength measures (p < 0.01), sprint times (p < 0.001 for 5 m; p < 0.05 for 30 m), COD (p < 0.01), and all RCOD parameters (p < 0.05) except the RCOD fatigue index. However, vertical jump parameters and limb volumes remained unchanged relative to controls. It may be concluded that adding biweekly elastic band training to a standard conditioning regimen yields small gains in measures that likely have an important influence on handball performance, particularly the ability to sprint, change direction, and make repeated changes of direction. Accordingly, such simple exercises can usefully be adopted as a component of handball training.


Designing CoS1.035 Nanoparticles Anchored on N-Doped Carbon Dodecahedron as Dual-Enzyme Mimics for the Colorimetric Detection of H2O2 and Glutathione.
In recent years, the exploration of the nanozyme, an artificial enzyme with the structure and function of natural enzymes, has become a hot topic in this field. Although significant progress has been made, it is still a huge challenge to design nanozymes with multiple enzyme-like catalytic activities. In this work, we have successfully fabricated a colorimetric sensing platform to mimic peroxidase-like and oxidase-like activities by the CoS1.035 nanoparticles decorated N-doped carbon framework porous dodecahedrons (abbreviated to CoS1.035/N-C PDHs). And the catalytic mechanism of CoS1.035/N-C PDHs toward the peroxidase-like and oxidase-like activities is systematically explored. The results display that CoS1.035/N-C PDHs can catalyze the oxidation of the colorless substrate 3,3,'5,5'-tetramethylbenzidine (TMB) into blue oxidized TMB (ox-TMB) by disintegrating H2O2 or the physically/chemically absorbed O2 into different ROS species (·OH or O2 ·-) in the presence or absence of H2O2. Therefore, on the basis of the dual-enzyme mimic activities of CoS1.035/N-C PDHs, the bifunctional colorimetric sensing platform is established for H2O2 detection with a wide linear range of 0.5-120 μM and glutathione detection with a linear range of 1-60 μM, respectively. This work provides an efficient platform for dual-enzyme mimics, expanding the application prospect of Co-based chalcogenides as enzyme mimics in biosensing, medical diagnosis, and environment monitoring.


Chemical characteristics of Salvia miltiorrhiza (Danshen) collected from different locations in China.
The chemical characteristics of Salvia miltiorrhiza , also called "danshen" in China, were investigated on the basis of the simultaneous quantitative determination of 13 hydrophilic and lipophilic compounds, namely, protocatechuic acid, protocatechuic aldehyde, caffeic acid, ferulic acid, isoferulic acid, rosmarinic acid, salvianolic acid B, salvianolic acid A, dihydrotanshinone I, przewalskin, cryptotanshinone, tanshinone I, and tanshinone IIA, in 74 samples collected from different locations using ultraperformance liquid chromatography (UPLC). Hierarchical clustering analysis based on 13 investigated compounds and the similarity of the entire chromatographic pattern showed that S. miltiorrhiza was significantly different from Salvia przewalskii , an adulterant of danshen. The chemical characteristics of S. miltiorrhiza collected from different locations in China were revealed, and salvianolic acid B, rosmarinic acid, cryptotanshinone, and tanshinones I and IIA were optimized as markers for the evaluation, which is helpful in the quality control of S. miltiorrhiza.


Copper-Catalyzed Aerobic C(sp3)-H Oxidation of β-(Alkoxy)imino Carbonyl Compounds.
Direct oxidation of the C(sp3)-H bond of β-(alkoxy)imino carbonyl compounds using copper acetate and molecular oxygen has been established. The protocol features a broad substrate scope and generates 1-imino-2,3-dicarbonyls in good to excellent yields.


Reliability of urinary albumin, total protein, and creatinine assays after prolonged storage: the Family Investigation of Nephropathy and Diabetes.
This study investigated the effect of long-term storage at -70 degrees C on urinary albumin, protein, and creatinine measurements in the Family Investigation of Nephropathy and Diabetes, a multicenter study designed to identify genes for diabetic nephropathy. Spot urine samples were collected at eight centers and shipped overnight on ice packs to a central laboratory. Samples were aliquotted and frozen at -70 degrees C for a median of 8 d before initial assay. As part of quality control procedures to determine interassay variability, 351 replicate samples were retrieved from storage at -70 degrees C after a median storage time between original and quality control analyses of 126 d (range 28 to 869 d). Freezer time was characterized as the difference in days between the initial assay and quality control assay. Percentage difference [(quality control - original/original) x 100%] between samples was regressed on storage time and adjusted for original value, age, race, gender, hypertension, and diabetes. After adjustment, freezer time per 30 d was associated with small decreases in percentage difference of urinary albumin (0.25%, P = 0.02), total protein (0.23%, P = 0.02), and albumin-to-creatinine ratio (0.34%, P = 0.001). Urinary creatinine levels were not affected by freezer time (P = 0.25). Measurements of urinary albumin, total protein, and albumin-to-creatinine ratio are minimally affected by storage at -70 degrees C for approximately 2.5 yr. Prolonged storage results in small decreases of urinary albumin and protein that do not substantially affect phenotype classification of overt renal disease.


Technical Note: The first live treatment on a 1.0 Tesla inline MRI-linac.
This work describes the first live imaging and radiation delivery performed on a prototype 1.0 T inline MRI-Linac system in a rat brain tumor model, which was conducted on 29 January 2019. A human scale 1.0 T MRI-Linac was adapted to be suitable for animal studies via a specially constructed open 6-channel receiver radiofrequency (RF) coil. A Fischer rat injected with 9L glioma cells in the right hemisphere was imaged and irradiated at day 11 post surgery as part of a larger cohort survival study. The rat was anesthetized and positioned at the iscocenter of the MRI-Linac. Imaging was used to localize the brain and confirm the presence of a tumor following the administration of a gadolinium nanoparticle contrast agent. A single dose of 10 Gy was delivered using a 2.25 cm × 2.90 cm radiation field covering the whole brain and verified with radiosensitive film in situ. Real-time imaging was used throughout the irradiation period to monitor the animal and target position. The signal-to-noise ratio (SNR) measured in the rat brain was 38. Postcontrast imaging was able to demonstrate a tumor of 5 mm diameter in the upper right hemisphere of the brain approximately 45 min after administration of the nanoparticles. The radiation beam had no impact on SNR and images at the rate of 2 Hz were effective in monitoring both respiration and intrafractional motion. In vivo film dosimetry confirmed the intended dose delivery. The total procedure time was 35 min. We have successfully used MRI guidance to localize and subsequently deliver a radiation field to the whole brain of a rat with a right hemispheric tumor. Real-time imaging during beam on was of sufficient quality to monitor breathing and perform exception gating of the treatment. This represents the first live use of a high field inline MRI-Linac.


Symposium on "parental education" at the ICCH17.
This symposium report provides a brief overview of the six programmes and studies on parental education and maternal health services within the circumpolar region presented in the symposium "parental education" at the 17th International Congress of Circumpolar Health in Copenhagen, Denmark, August 2018.


Complete Mitochondrial Genomes and Phylogenetic Positions of Two Longicorn Beetles, Anoplophora glabripennis and Demonax pseudonotabilis (Coleoptera: Cerambycidae).
Anoplophora glabripennis (Motschulsky, 1854) and Demonax pseudonotabilis Gressitt & Rondon, 1970 are two commonly found longicorn beetles from China. However, the lack of sufficient molecular data hinders the understanding of their evolution and phylogenetic relationships with other species of Cerambycidae. This study sequenced and assembled the complete mitochondrial genomes of the two species using the next-generation sequencing method. The mitogenomes of A. glabripennis and D. pseudonotabilis are 15,622 bp and 15,527 bp in length, respectively. The mitochondrial gene content and gene order of A. glabripennis and D. pseudonotabilis are highly conserved with other sequenced longicorn beetles. The calculation of nonsynonymous (Ka) and synonymous (Ks) substitution rates in PCGs indicated the existence of purifying selection in the two longicorn beetles. The phylogenetic analysis was conducted using the protein-coding gene sequences from available mitogenomes of Cerambycidae. The two species sequenced in this study are, respectively, grouped with their relatives from the same subfamily. The monophyly of Cerambycinae, Dorcasominae, Lamiinae, and Necydalinae was well-supported, whereas Lepturinae, Prioninae, and Spondylidinae were recovered as paraphyletic.


Trends in elevated triglyceride in adults: United States, 2001-2012.
The percentage of adults aged 20 and over with elevated triglyceride (150 mg/dL or more) declined from 33.3% during 2001-2004 to 25.1% during 2009-2012. Percentages with elevated triglyceride decreased for both men and women-among men, from 37.3% for 2001-2004 to 28.7% for 2009-2012, and among women, from 29.3% for 2001-2004 to 21.5% for 2009-2012. For adults aged 60 and over, declines in elevated triglyceride levels were seen in both men (from 39.9% during 2001-2004 to 24.8% during 2009-2012) and women (from 43.5% during 2001-2004 to 30.9% during 2009-2012). Declines in elevated triglyceride levels were observed in overweight and obese men and women between 2001-2004 and 2009-2012.


Hepatitis B virus X protein plays an important role in gastric ulcers.
Hepatitis B virus (HBV) infects many individuals globally each year. Researchers usually focus on the relationship between HBV and liver diseases. In this study, we investigated the effects of HBV infection on gastric mucosa. We detected the levels of HBX protein and mRNA in specimens from sixty-four chronic hepatitis B patients (CHB) with gastric ulcers. We confirmed that HBX could aggravate gastric ulcers according to clinicopathological parameters. In addition, we constructed the pcDNA3.1-HBX plasmid and transfected it into GES-1, a gastric mucosal cell line. The results indicated that HBX could induce apoptosis and G1 arrest in GES-1 cells. Insights into the mechanism of HBX action in GES-1 cells were obtained using western blot analysis.


[Endoscopic endonasal surgery for clival tumor].
To review our experience with endoscopic endonasal approach for surgical management of clival tumors. Twenty-four patients with clival tumors treated by endoscopic endonasal surgery between August 2002 and November 2005 were studied prospectively. The operative technique was described in detail. There were 5 chordoma, 2 ossifying fibroma, 1 meningioma, 1 craniopharyngioma, 1 hemangioblastoma, 6 squamous cancer, 2 chondrosarcoma, 2 chondrosarcoma, 1 lymphoma, 1 malignant giant cell tumor and 2 metastatic carcinoma. Total tumor removal was obtained in 22 cases, subtotal removal in 2 case. Follow-up ranged 12 to 51 months. Three patients dead. Five patients with total removal recurred, one of them dead. Two patients with subtotal removal dead, one with chondrosarcoma and one with chordoma. The complications included subarachnoid hemorrhage in 1 patient, and transient cerebrospinal leakage in 2 cases. The use of nasoendoscopy to perform clival tumor surgery is not only limited to the minimally invasive aspect, it also provides better visualization of deeper structures in the skull base, provides the ability to 'look around corners' and wide exposed field. This approach permits us to manage clival lesions properly.


Expression, purification, crystallization and preliminary X-ray crystallographic studies of a cold-adapted aspartate carbamoyltransferase from Moritella profunda.
Aspartate carbamoyltransferase (ATCase) catalyzes the carbamoylation of the alpha-amino group of L-aspartate by carbamoyl phosphate (CP) to yield N-carbamoyl-L-aspartate and orthophosphate in the first step of de novo pyrimidine biosynthesis. Apart from its key role in nucleotide metabolism, the enzyme is generally regarded as a model system in the study of proteins exhibiting allosteric behaviour. Here, the successful preparation, crystallization and diffraction data collection of the ATCase from the psychrophilic bacterium Moritella profunda are reported. To date, there is no structural representative of a cold-adapted ATCase. The structure of M. profunda ATCase is thus expected to provide important insights into the molecular basis of allosteric activity at low temperatures. Furthermore, through comparisons with the recently reported structure of an extremely thermostable ATCase from Sulfolobus acidocaldarius, it is hoped to contribute to general principles governing protein adaptation to extreme environments. A complete native data to 2.85 A resolution showed that the crystal belongs to space group P3(2)21, with unit-cell parameters a = 129.25, b = 129.25, c = 207.23 A, alpha = beta = 90, gamma = 120 degrees, and that it contains three catalytic and three regulatory subunits per asymmetric unit. The three-dimensional structure of the Escherichia coli ATCase was sufficient to solve the structure of the M. profunda ATCase via the molecular-replacement method and to obtain electron density of good quality.


An R-Based Landscape Validation of a Competing Risk Model.
The Cox proportional hazard model is widely applied for survival analyses in clinical settings, but it is not able to cope with multiple survival outcomes. Different from the traditional Cox proportional hazard model, competing risk models consider the presence of competing events and their combination with a nomogram, a graphical calculating device, which is a useful tool for clinicians to conduct a precise prognostic prediction. In this study, we report a method for establishing the competing risk nomogram, that is, the evaluation of its discrimination (i.e., concordance index and area under the curve) and calibration (i.e., calibration curves) abilities, as well as the net benefit (i.e., decision curve analysis). In addition, internal validation using bootstrap resamples of the original dataset and external validation using an external dataset of the established competing risk nomogram were also performed to demonstrate its extrapolation ability. The competing risk nomogram should serve as a useful tool for clinicians to predict prognosis with the consideration of competing risks.


Fc receptors are major mediators of antibody based inflammation in autoimmunity.
There is now renewed interest in the role of antibodies in autoimmunity. Recent compelling evidence indicates that autoantibodies and the effector mechanisms they induce, for example, Fc receptor activation of leukocytes and/or the complement cascade, are central players in the development of autoimmunity, by perpetuating inflammation and perhaps even regulating the process itself. Of increasing interest are Fc receptors, which have been more closely investigated in the past decade using recombinant proteins, gene deficient mice and mouse models of human disease. These analyses point towards major roles of Fc receptors in antibody hypersensitivity reactions and by extension autoimmune disease, and they reveal opportunities in the development of novel therapeutic approaches in the treatment of autoimmune diseases.


Successful Transcatheter Arterial Radioembolization of Hepatocellular Carcinoma Via Left Internal Mammary Artery: A Case Report.
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Late-stage presentation, co-morbidities, and limited donor availability enable only a few patients to receive curative therapies. HCC is treated with liver resection and transplantation as the first line of treatment. Patients in advanced stages, on the other hand, are treated with a variety of locoregional treatments. Transarterial embolization (TAE), transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) are different modalities of locoregional therapy for HCC with robust collateral circulation. One of the characteristics of HCC is that it is hypervascular, therefore, parasitic supply is not unusual. The left internal mammary artery (LIMA) is considered to be an uncommon parasitic supply in HCC. While TACE has been extensively reviewed in the literature, herein we report a successful case of TARE via the LIMA which was a safe and practical alternative for a patient with HCC.


Population pharmacokinetics model for escitalopram in Chinese psychiatric patients: effect of CYP2C19 and age.
Objective: To establish a population pharmacokinetic model in Chinese psychiatric patients to characterize escitalopram pharmacokinetic profile to identify factors influencing drug exposure, and through simulation to compare the results with the established therapeutic reference range. Methods: Demographic information, dosing regimen, CYP2C19 genotype, concomitant medications, and liver and kidney function indicators were retrospectively collected for inpatients taking escitalopram with therapeutic drug monitoring from 2018 to 2021. Nonlinear mixed-effects modeling was used to model the pharmacokinetic characteristics of escitalopram. Goodness-of-fit plots, bootstrapping, and normalized prediction distribution errors were used to evaluate the model. Simulation for different dosing regimens was based on the final estimations. Results: The study comprised 106 patients and 337 measurements of serum sample. A structural model with one compartment with first-order absorption and elimination described the data adequately. The population-estimated apparent volume of distribution and apparent clearance were 815 and 16.3 L/h, respectively. Age and CYP2C19 phenotype had a significant effect on the apparent clearance (CL/F). CL/F of escitalopram decreased with increased age, and CL/F of poor metabolizer patients was significantly lower than in extensive and immediate metabolizer patients. The final model-based simulation showed that the daily dose of adolescents with poor metabolizer might be as high as 15 mg or 20 mg and referring to the therapeutic range for adults may result in overdose and a high risk of adverse effects in older patients. Conclusion: A population pharmacokinetics model of escitalopram was successfully created for the Chinese population. Depending on the age of the patients, CYP2C19 genotype and serum drug concentrations throughout treatment are required for adequate individualization of dosing regimens. When developing a regimen for older patients, especially those who are poor metabolizers, vigilance is required.


Value of Combined Detection of Serum CEA, CA72-4, CA19-9 and TSGF in the Diagnosis of Gastric Cancer.
To explore whether combined detection of serum tumor markers (CEA, CA72-4, CA19-9 and TSGF) improve the sensitivity and accuracy in the diagnosis of gastric cancer (GC). An automatic chemiluminescence immune analyzer with matched kits were used to determine the levels of serum CEA, CA72-4, CA19-9 and TSGF in 45 patients with gastric cancer (GC group), 40 patients with gastric benign diseases (GBD group) hospitalized in the same period and 30 healthy people undergoing a physical examination. The values of those 4 tumor markers in the diagnosis of gastric cancer was analyzed. The levels of serum CEA, CA72-4, CA19-9 and TSGF of the GC group were higher than those of the GBD group and healthy examined people and the differences were significant (P<0.001). The area under receiver operating characteristic (ROC) curves for single detection of CEA, CA72-4, CA19-9 and TSGF in the diagnosis of GC was 0.833, 0.805, 0.810 and 0.839, respectively. The optimal cutoff values for these 4 indices were 2.36 ng/mL, 3.06 U/mL, 5.72 U/ mL and 60.7 U/mL, respectively. With combined detection of tumor markers, the diagnostic power of those 4 indices was best, with an area under the ROC curve of 0.913 (95%CI 0.866~0.985), a sensitivity of 88.9% and a diagnostic accuracy of 90.4%. Combined detection of serum CEA, CA72-4, CA19-9 and TSGF increases the sensitivity and accuracy in diagnosis of GC, so it can be regarded as the important means for early diagnosis.


ANG II and calmodulin/CaMKII regulate surface expression and functional activity of NBCe1 via separate means.
We recently reported that ANG II inhibits NBCe1 current and surface expression in Xenopus laevis oocytes (Perry C, Blaine J, Le H, and Grichtchenko II. Am J Physiol Renal Physiol 290: F417-F427, 2006). Here, we investigated mechanisms of ANG II-induced changes in NBCe1 surface expression. We showed that the PKC inhibitor GF109203X blocks and EGTA reduces surface cotransporter loss in ANG II-treated oocytes, suggesting roles for PKC and Ca(2+). Using the endosomal marker FM 4-64 and enhanced green fluorescent protein (EGFP)-tagged NBCe1, we showed that ANG II stimulates endocytosis of NBCe1. To eliminate the possibility that ANG II inhibits NBCe1 recycling, we demonstrated that the recycling inhibitor monensin decreases surface expression, accumulates NBCe1-EGFP in endosomes, and inhibits NBCe1 current. Monensin and ANG II applied together produce greater inhibition of NBCe1 current than either did alone. This additive effect of monensin and ANG II suggests that ANG II stimulates internalization of NBCe1. We used the calmodulin (CaM) antagonist W13, which controls recycling by blocking the exit of the endocytosed cargo from early endosomes, to determine the role of CaM in NBCe1 trafficking. We demonstrated that W13 decreases surface expression of NBCe1, accumulates NBCe1-EGFP in endosomal-like formations, and inhibits NBCe1 current. W13 and ANG II applied together produce greater inhibition of NBCe1 current than either does alone, while W13 and monensin applied together do not. The additive effect of ANG II and W13 and lack of additive effect of monensin and W13 suggest that CaM is not involved in ANG II stimulation of internalization but controls recycling of endocytosed NBCe1. The CaM-activated enzyme CaM kinase II (CaMKII) applied with ANG II also gives an additive inhibitory effect, suggesting a role for CaMKII in NBCe1 recycling.


Proximal Crohn's disease: review of the clinicopathologic features and therapy.
Crohn's disease in the proximal region of the digestive tract is uncommon. Better diagnostically procedures and more careful histologic examination has led to a higher detection of proximal Crohn's disease. The diagnosis is based on symptoms, endoscopy with serial sections, or double contrast radiography. The most common histologic finding for this diagnosis are granulomas in the mucosa in Helicobacter pylori-negative patients, but the granulomas are not always frequently detected. Endoscopic lesions in the proximal regions look like the lesions that could be found in the distal regions. Notching in the duodenal folds could be a strong indication for Crohn's desease. Radiological lesions are not always characteristic, but should be used in combination with endoscopy. Stenosis is an important complication, but fistula formation and pseudodiverticular formation is possible. There is no uniform medical therapy, but the regular anti-inflammatory management for Crohn's disease is most often used. Sometimes surgery is needed.


Mapping of the human NMDAR2B receptor subunit gene (GRIN2B) to chromosome 12p12.
The N-methyl-D-aspartate (NMDA) receptor channel is essential for synaptic transmission and synaptic plasticity underlying memory, learning, and development. Three subunits of the NMDA receptor channel, NMDAR2A, NMDAR2B, and NMDAR2C (NR2A, NR2B, and NR2C), previously identified in mouse by cDNA cloning and expression, share a high level of homology, although their patterns of expression within the brain may differ. In the present work we report the localization of the gene encoding the human NMDAR2B receptor subunit (called GRIN2B for glutamate receptor, ionotropic, N-methyl-D-aspartate 2B) to chromosome 12p12 by in situ hybridization and somatic cell hybrids.


Cell interactions in psoriasis.
Products of the HLA-D gene, the la or DR antigens, have been shown to control interactions between certain cells with immune functions. Three HLA-D alleles have been reported to be associated with a markedly increased relative risk in psoriatic individuals. We report the existence of apparently unique anatomic interactions between lymphocytes and basal keratinocytes, between Langerhans' cells and basal keratinocytes, and between Langerhans' cells and lymphocytes, deduced on the basis of (1) characteristic cytoplasmic processes extending from one cell into the cytoplasm of adjacent cells, with frequent absence of the intervening plasma membrane at the apexes of these processes, and (2) intimate apposition of the plasma membranes between the interaction cells over a large surface area. These interactions were noted in five of ten untreated psoriatic patients (three of four patients with Koebner's phenomenon) and in one of six treated psoriatic patients, but in none of 17 controls. Intercellular space abnormalities, probably secondary to excessive proteolytic enzyme release, and basal keratinocyte herniations in psoriasis may result from these anatomic interactions.


Gratitude buffers the effects of stressful life events and deviant peer affiliation on adolescents' non-suicidal self-injury.
Although stressful life events have been shown to be a key risk factor for adolescent NSSI, the potential mediators and moderators of this relationship are unclear. Based on the social development theory and the organism-environment interaction model, we tested whether the link between stressful life events and adolescent NSSI was explained in part by deviant peer affiliation, and whether this process was buffered by gratitude. Chinese adolescents (N = 854; M age = 16.35; 68.50% female) anonymously completed questionnaires to assess the study variables. The present study demonstrated that stressful life events was linked to NSSI in part because of deviant peer affiliation, and high gratitude was a key protective factor to buffer this indirect effect. Teaching gratitude may be a helpful component of prevention and intervention programs to reduce adolescent NSSI.


The negative impact of global perceptions of and daily care-related family conflict on Hispanic caregivers: familism as a potential moderator.
Using selected concepts from Pearlin's care giving stress model and incorporating a daily stress-reactivity perspective, the current study surveyed Hispanic family caregivers (HCGs) to: (a) document the occurrence of family disagreements regarding care; (b) examine the impact of family disagreements regarding care on HCGs' emotional/physical well being; and (c) determine the moderating role of familism - whether strong familism beliefs buffer or exacerbate the negative impact of family disagreements on HCGs. Participants (n = 67) reported their daily experiences of family disagreements regarding care, depressive symptoms, feelings of burden, and physical health symptoms on eight consecutive survey days; and, in a separate survey, reported their global perceptions of family disagreements regarding care and their familism beliefs. Multilevel-modeling indicated (a) a significant link between global perceptions of family disagreement regarding care and greater depressive symptoms, feelings of burden, and physical health symptoms and (b) significant moderating (i.e., exacerbating) effects of familism at the daily level suggesting that HCGs with stronger familism beliefs are more reactive to daily care-related family disagreement occurrences. The findings from the current study suggest that family disagreement regarding care is a salient aspect of the context of care giving for HCGs, and is linked to depressive symptoms, feelings of burden, and physical health symptoms. Familism may play an exacerbating role in this link. Interpretations of the results and implications for research and intervention are offered.


Intestinal inflammation modulates expression of 11beta-hydroxysteroid dehydrogenase in murine gut.
The effect of glucocorticoids is controlled at the pre-receptor level by the activity of 11beta-hydroxysteroid dehydrogenase (11HSD). The isoform 11HSD1 is an NADP+ -dependent oxidoreductase, usually reductase, that amplifies the action of glucocorticoids due to reduction of the biologically inactive 11-oxo derivatives cortisone and 11-dehydrocorticosterone to cortisol and corticosterone. The NAD+ -dependent isoform (11HSD2) is an oxidase that restrains the effect of hormones due to 11beta-oxidation of cortisol and corticosterone to their 11-oxo derivatives. Although the immunosuppressive and anti-inflammatory effects of glucocorticoids are well known, the relationship between inflammation and local metabolism of glucocorticoids is not well understood. In this study, we demonstrated that colitis induced by dextran sulfate sodium modulates colonic 11HSD1. Experimentally induced intestinal inflammation stimulated colonic NADP+ -dependent but not NAD+ -dependent 11HSD activity. Colonic 11HSD1 mRNA was increased, whereas 11HSD2 mRNA was not changed. Additional parallel studies revealed a similar pattern of 11HSD1 mRNA induction in mesenteric lymph nodes and intestinal intraepithelial lymphocytes, but not in spleen and peritoneal macrophages. These data suggest that inflammation modulates local metabolism of glucocorticoid and support the notion that pre-receptor regulation of endogenous corticosteroids might play a role in inflammatory processes.


Inconsistency in the expression pattern of a five-lncRNA signature as a potential diagnostic biomarker for gastric cancer patients in bioinformatics and in vitro.
Due to diagnosis of gastric cancer in advanced stages as well as its poor prognosis, finding biomarkers is essential. In this study, using the TCGA RNAseq data of gastric cancer patients, we evaluated the diagnostic value of lncRNAs that had differential expression. We evaluated P-value, FDR, and log fold change for whole transcripts. Next, by comparison of the RNAseq gene names with the total known lncRNA names, we identified differential expressed lncRNAs. Following this, specificity and sensitivity for lncRNAs coming from the previous step were calculated. For more confirmation, we predicted target genes and performed GO and KEGG signaling pathway analysis. In the end, we examined reliability and consistency of expression of this signature in three gastric cancer cell lines and one of them in twenty tumors and tumor-adjacent normal tissue samples using qRT-PCR. Five lncRNAs had proper sensitivity and specificity and had target genes involved in cancer-related signaling pathways; however, they showed different expression patterns in TCGA data and in vitro. The results of our study demonstrated that the five-lncRNAs PART1, UCA1, DIRC3, HOTAIR, and HOXA11AS require more investigation to be confirmed as diagnostic biomarkers in gastric cancer.


Extracorporeal membrane oxygenation for ARDS in adults.
A 41-year-old woman presents with severe community-acquired pneumococcal pneumonia. Chest radiography reveals diffuse bilateral infiltrates, and hypoxemic respiratory failure develops despite appropriate antibiotic therapy. She is intubated and mechanical ventilation is initiated with a volume- and pressure-limited approach for the acute respiratory distress syndrome (ARDS). Over the ensuing 24 hours, her partial pressure of arterial oxygen (Pao2) decreases to 40 mm Hg, despite ventilatory support with a fraction of inspired oxygen (Fio2) of 1.0 and a positive end-expiratory pressure (PEEP) of 20 cm of water. She is placed in the prone position and a neuromuscular blocking agent is administered, without improvement in her Pao2. An intensive care specialist recommends the initiation of extracorporeal membrane oxygenation (ECMO).


A Perspective on Bone Morphogenetic Proteins: Dilemma behind Cancer- related Responses.
Bone morphogenetic proteins are a center of serious concern and are known to execute various cancer-related issues. The BMP signaling cascades have become more unpredictable as a result of their pleiotropic and risky characteristics, particularly when it comes to cancer responses. This perspective discusses the current therapeutic implications, emphasizes different cellular aspects that impact the failures of the current drug treatments, and speculates on future research avenues that include novel strategies like metabolomic studies and bio-mimetic peptide therapeutics to mitigate cancerous outcomes.


A deductive database system for analyzing human nucleotide sequence data.
The analysis of the human genome is one of the most significant topics in both biology and medical science. There is a growing need for a well-designed database system for searching and analyzing the human genome data. We developed a deductive database system to search and analyze nucleotide sequence data derived from the GenBank primates data. A deductive database system is a next generation one and it contains an inference mechanism that can handle problems beyond the capabilities of classical database systems. Database queries are described in logical rules. These rules are simple even for molecular biologists who are not experts in computer programs because they are declarative and do not require the procedural commands that are usually used in computer programs. Furthermore, queries based on logical rules are powerful enough to express complicated biological problems. Particularly, recursive rules are suitable for examining secondary structures of nucleotide sequences. In our analysis of TfR's IRE, we noted five stem-and-loop structures.


The Eighth Edition of the American Joint Committee on Cancer Distant Metastases Stage Classification for Metastatic Pancreatic Neuroendocrine Tumors Might Be Feasible for Metastatic Pancreatic Ductal Adenocarcinomas.
Significant modifications have been made to the 8th edition of the American Joint Committee on Cancer (AJCC) distant metastases (M) stage classification for metastatic pancreatic neuroendocrine tumors (PanNETs). We aimed to validate this revised classification among metastatic PanNET patients using the Surveillance, Epidemiology, and End Results database. We further sought to evaluate the feasibility of applying this classification to metastatic pancreatic neuroendocrine carcinoma (PanNEC) and pancreatic ductal adenocarcinoma (PDAC) patients. Stage IV pancreatic neuroendocrine neoplasm (PanNEN, including G1/G2 PanNET and G3 PanNEC classified according to the World Health Organization [WHO] 2010 grading scheme) and PDAC patients with metastatic disease diagnosed between 2010 and 2015 were identified and restaged according to the revised M stage classification for PanNET. Overall survival (OS) was compared using Kaplan-Meier analysis and log-rank test. Uni- and multivariate Cox regression models were utilized to identify prognostic factors. A total of 1,371 stage IV PanNEN and 634 PDAC patients were included. Among PanNEN patients, liver (75.0%) was the most common metastatic site, followed by distant lymph nodes (8.5%), lung (8.4%), bone (7.3%), and brain (1.0%). The 5-year OS for PanNET patients with M1a, M1b, and M1c stage was 44.15, 53.32, and 19.70%, respectively. However, survival comparison showed no significant difference between M1a and M1b stages among PanNET patients. Similar findings were noted after applying this classification to PanNEC patients. Multivariate analysis showed that the age at diagnosis and the number of distant metastatic sites were independent prognostic factors for metastatic PanNEN patients. Interestingly, excellent survival discrimination by M stage among stage IV PDAC patients was noted (M1a vs. M1b vs. M1c, 5-year OS: 5.42, 2.46, and 0%, respectively). Our study is the first large sample-based validation of the AJCC 8th M stage classification for PanNET. The revised classification did not effectively stratify metastatic PanNEN patients. However, further study is warranted to validate this classification for PanNET patients according to the WHO 2017 classification. Interestingly, the revised M stage classification might be feasible for PDAC patients with metastatic disease.


Binaural interference in bilateral cochlear-implant listeners.
This work was aimed at determining whether binaural interference occurs in electric hearing, and if so, whether it occurs as a consequence of perceptual grouping (central explanation) or if it is related to the spread of excitation in the cochlea (peripheral explanation). Six bilateral cochlear-implant listeners completed a series of experiments in which they judged the lateral position of a target pulse train, lateralized via interaural time or level differences, in the presence of an interfering diotic pulse train. The target and interferer were presented at widely separated electrode pairs (one basal and one apical). The results are broadly similar to those reported for acoustic hearing. All listeners but one showed significant binaural interference in at least one of the stimulus conditions. In all cases of interference, a robust recovery was observed when the interferer was presented as part of an ongoing stream of identical pulse trains, suggesting that the interference was at least partly centrally mediated. Overall, the results suggest that both simultaneous and sequential grouping mechanisms operate in electric hearing, at least for stimuli with a wide tonotopic separation.


Diversity of the Burkholderia cepacia complex and implications for risk assessment of biological control strains.
The Burkholderia cepacia complex (Bcc) consists of several species of closely related and extremely versatile gram-negative bacteria found naturally in soil, water, and the rhizosphere of plants. Strains of Bcc have been used in biological control of plant diseases and bioremediation, while some strains are plant pathogens or opportunistic pathogens of humans with cystic fibrosis. The ecological versatility of these bacteria is likely due to their unusually large genomes, which are often comprised of several (typically two or three) large replicons, as well as their ability to use a large array of compounds as sole carbon sources. The original species B. cepacia has been split into eight genetic species (genomovars), including five named species, but taxonomic distinctions have not enabled biological control strains to be clearly distinguished from human pathogenic strains. This has led to a reassessment of the risk of several strains registered by the U.S. Environmental Protection Agency for biological control. We review the biology of Bcc bacteria, especially how our growing knowledge of Bcc ecology and pathogenicity might be used in risk assessment. The capability of this bacterial complex to cause disease in plants and humans, as well as to control plant diseases, affords a rare opportunity to explore traits that may function in all three environments.


Facile control of C₂H₅OH sensing characteristics by decorating discrete Ag nanoclusters on SnO₂ nanowire networks.
The effect of Ag decoration on the gas sensing characteristics of SnO(2) nanowire (NW) networks was investigated. The Ag layers with thicknesses of 5-50 nm were uniformly coated on the surface of SnO(2) NWs via e-beam evaporation, which were converted into isolated or continuous configurations of Ag islands by heat treatment at 450 °C for 2 h. The SnO(2) NWs decorated by isolated Ag nano-islands displayed a 3.7-fold enhancement in gas response to 100 ppm C(2)H(5)OH at 450 °C compared to pristine SnO(2) NWs. In contrast, as the Ag decoration layers became continuous, the response to C(2)H(5)OH decreased significantly. The enhancement and deterioration of the C(2)H(5)OH sensing characteristics by the introduction of the Ag decoration layer were strongly governed by the morphological configurations of the Ag catalysts on SnO(2) NWs and their sensitization mechanism.


[Successful CYVADIC combination chemotherapy of metastatic pulmonary lesions involving a mediastinal leiomyosarcoma--a case report].
Discussed is a 34-year-old man who hospitalized for manifesting the superior vena cava syndrome. Chest radiograph and chest CT scan revealed a gross tumor shadow in the superior mediastinum and a tiny shadow in the right lung. Superior vena cavography showed intimal stenosis, irregularities, and stiffness of the superior vena cava. Thus, radiotherapy applied to primary lesion of the mediastinum was provided to relieve his complaints. One year later, predominant metastatic pulmonary lesions and skin lesions developed. Light and electron microscopic findings of a biopsied specimen of the skin lesion were consistent with leiomyosarcoma. CYVADIC combination chemotherapy reduced the pulmonary metastatic lesions dramatically. The literature of mediastinal leiomyosarcoma is reviewed and the origin of this tumor is discussed.


Clinical characteristics of childhood asthma.
A prospective study was undertaken of 298 asthmatic children attending a paediatric allergy clinic in Bloemfontein. A detailed history was obtained, and skin tests were performed. Male predominance and an early age of onset were confirmed. Symptomatic allergic rhinitis was an extremely common finding. A family history of allergy was obtained in over 90% of cases. Respiratory tract infections, changes in the weather and exercise were found to be the most common asthma-inducing factors. Common allergens were grass pollen (63%) and animal danders. House-dust mite (25%) and dietary allergens (less than 20%) were relatively uncommon. The failure to recognise the symptoms of asthma in children, particularly young children, was identified as an ongoing problem.


Nanophotosensitizers Composed of Phenyl Boronic Acid Pinacol Ester-Conjugated Chitosan Oligosaccharide via Thioketal Linker for Reactive Oxygen Species-Sensitive Delivery of Chlorin e6 against Oral Cancer Cells.
Chlorin E6 (Ce6)-incorporated nanophotosensitizers were fabricated for application in photodynamic therapy (PDT) of oral cancer cells. For this purpose, chitosan oligosaccharide (COS) was conjugated with hydrophobic and reactive oxygen species (ROS)-sensitive moieties, such as phenyl boronic acid pinacol ester (PBAP) via a thioketal linker (COSthPBAP). ThdCOOH was conjugated with PBAP to produce ThdCOOH-PBAP conjugates and then attached to amine groups of COS to produce a COSthPBAP copolymer. Ce6-incorporated nanophotosensitizers using the COSthPBAP copolymer were fabricated through the nanoprecipitation and dialysis methods. The Ce6-incorporated COSthPBAP nanophotosensitizers had a small diameter of less than 200 nm with a mono-modal distribution pattern. However, it became a multimodal and/or irregular distribution pattern when H2O2 was added. In a morphological observation using TEM, the nanophotosensitizers were disintegrated by the addition of H2O2, indicating that the COSthPBAP nanophotosensitizers had ROS sensitivity. In addition, the Ce6 release rate from the COSthPBAP nanophotosensitizers accelerated in the presence of H2O2. The SO generation was also higher in the nanophotosensitizers than in the free Ce6. Furthermore, the COSthPBAP nanophotosensitizers showed a higher intracellular Ce6 uptake ratio and ROS generation in all types of oral cancer cells. They efficiently inhibited the viability of oral cancer cells under light irradiation, but they did not significantly affect the viability of either normal cells or cancer cells in the absence of light irradiation. The COSthPBAP nanophotosensitizers showed a tumor-specific delivery capacity and fluorescence imaging of KB tumors in an in vivo animal tumor imaging study. We suggest that COSthPBAP nanophotosensitizers are promising candidates for the imaging and treatment of oral cancers.


Cryptosporidium Infection Increases the Risk for Chronic Diarrhea Among People Living With HIV in Southeast Asia: A Systematic Review and Meta-Analysis.
We conducted a systematic review research and meta-analysis to reveal the relationship between the risk of chronic diarrhea and Cryptosporidium infection in people living with HIV in Southeast Asia. We performed online peer-reviewed literature research from January 2005 to December 2017, which included PubMed, Science Direct, ProQuest, EBSCO, Cochrane, and Web of Science databases. Calculation of size effects in the meta-analysis was performed by STATA 13.0 software to estimate relative risks (RRs) with 95% confidence intervals (CIs) for any associations. Seven cross-sectional research articles were recruited in this study based on the inclusion and exclusion criteria. Our analysis revealed a significant relationship between cryptosporidiosis and the risk of chronic diarrhea in people living with HIV, with RR = 1.325; 95% CI = 1.157 to 1.517; and P < .000. Our results suggested that cryptosporidiosis increases the risk of chronic diarrhea, and low CD4+ lymphocyte cell counts aggravate the degree of diarrhea. Therefore, clinicians should be more aware in treating HIV-positive people, especially those with low CD4+ cell counts, and we suggest that Cryptosporidium laboratory examinations be conducted immediately.


Clinical audit of leg ulceration prevalence in a community area: a case study of good practice.
This article presents the findings of an audit on venous leg ulceration prevalence in a community area as a framework for discussing the concept and importance of audit as a tool to inform practice and as a means to benchmark care against national or international standards. It is hoped that the discussed audit will practically demonstrate how such procedures can be implemented in practice for those who have not yet undertaken it, as well as highlighting the unexpected extra benefits of this type of qualitative data collection that can often unexpectedly inform practice and influence change. Audit can be used to measure, monitor and disseminate evidence-based practice across community localities, facilitating the identification of learning needs and the instigation of clinical change, thereby prioritising patient needs by ensuring safety through the benchmarking of clinical practice.


Pretreatment of sivelestat sodium hydrate improves the lung microcirculation and alveolar damage in lipopolysaccharide-induced acute lung inflammation in hamsters.
Damage to the lung microcirculation and alveoli caused by activated leukocytes is known to play an important role in the development of acute lung injury (ALI). The aim of this study is to evaluate the difference in the effect of pretreatment and posttreatment of a synthetic neutrophil elastase inhibitor sivelestat on ALI. Hamsters were instilled with 10.0 mg/kg of lipopolysaccharide (LPS) intratracheally for 1 h to simulate ALI. Two milligrams per kilogram of sivelestat was injected intraperitoneally either previously or after LPS infusion. One and 24 hours after the infusion of LPS, pulmonary microcirculation was observed under the intravital microscopy. In another series, the blood cell counts were evaluated. The adhesive leukocyte count on the endothelium was significantly lower in pretreatment group compared with control group (P < 0.01), whereas the difference was not significant in the posttreatment group. Similarly, the number of obstructed capillary was significantly lower in the pretreatment group (P < 0.01). The width of interstitium was significantly lower in the pretreatment and posttreatment group (P < 0.01 and 0.05, respectively). A comparison of white blood cell counts showed a better maintenance in pretreatment group (P < 0.05). Pretreatment of sivelestat demonstrated a protective effect on both intravascular and extravascular damage in the lung, whereas posttreatment only suppressed the latter damage.


Relative Age Effect is Modulated by Playing Position but is Not Related to Competitive Success in Elite Under-19 Handball Athletes.
This study aimed to verify the occurrence of the relative age effect (RAE) in male elite young handball athletes according to the playing position and its association with team performance in a World Championship. Data from 383 handball athletes from 24 countries who participated in the 7th World Men's Championship in the under-19 category were analyzed. RAE was investigated from the birth trimester of the athletes, their playing position, and final ranking in the Championship. The results showed an overrepresentation of athletes born in the first two trimesters (Q1 and Q2) (χ2(3) = 32.97; p < 0.001, ω = 0.29). The analysis of the athlete's position showed that most wings (χ2(3) = 18.37; p < 0.001, ω = 0.32) and backs (χ2(3) = 12.51; p = 0.006, ω = 0.34) were born in the first trimesters (Q1 and Q2). The ranking in the Championship presented no significant association with the date of the birth (p > 0.05). The results showed the existence of the RAE in youth handball elite athletes, especially for the back and wing positions. However, the strategy of selecting is questionable once the presence of RAE was not associated with competitive success.


RNA-mediated synthesis of palladium nanoparticles on Au surfaces.
RNA catalysts for the shape-controlled synthesis of Pd particles from the precursor complex trisdibenzylideneacetone dipalladium ([Pd2(DBA)3] were recently discovered in our laboratory (J. Am. Chem. Soc. 2005, 127, 17814-17818). In the work described here, RNA codes for hexagonal Pd platelets and Pd cubes were covalently immobilized on gold surfaces and evaluated for their activity toward particle synthesis. When coupled to gold via oligoethylene glycol linkers, both RNA sequences were able to catalyze the formation of Pd particles with the same shape control previously observed in solution. For low surface coverages, the average distance between RNA molecules on the surface was estimated at ca. 300 nm, yet large (e.g., dimensions of hundreds of nanometers) Pd hexagons and cubes still formed. This surprising result suggests that a single RNA molecule may be sufficient for nucleating and controlling the shapes of these particles. Finally, the use of surface-bound RNA as a tool for directing the orthogonal synthesis of materials on surfaces was demonstrated. Patterning the RNA code for Pd hexagons next to the code for Pd cubes, followed by incubation in a solution containing [Pd2(DBA)3], resulted in the spontaneous formation of spatially distinct spots of hexagonal and cubic particles.


Systematic Review and Meta-Analysis Program Based on Effectiveness of a Multidisciplinary Model of Care for Patients with Chronic Kidney Disease.
The effectiveness of the multidisciplinary nursing model in the nursing of chronic kidney disease (CKD) by using meta-analysis is explored. Relevant literatures that are in line with the multidisciplinary nursing model for CKD intervention are searched and screened from domestic and foreign literature databases such as Wanfang Medical Center, CNKNET, VIP, and PubMed, and Meta-analysis is conducted with RevMan 5.2 software. A total of 6 literatures are included, and the publication bias of the included literatures is low. Meta-analysis shows that the multidisciplinary group had a better Hb compliance rate, Hb level, Scr, eGFR, SBP, and DBP than the traditional group. The experimental results show that multidisciplinary nursing intervention can improve the nursing effect of patients with CKD and help to improve Hb, Scr, blood pressure, and glomerular filtration function of patients.


Mutagenesis identifies amino acid residues in extracellular loops and within the barrel lumen that determine voltage gating of porin from Haemophilus influenzae type b.
Porin (341 amino acids; M(r) 37 782) of Haemophilus influenzae type b mediates exchange of solutes between the external environment and the periplasm of this Gram-negative bacterium. Positively charged residues in the extracellular loops have been shown to be involved in the voltage gating of this protein. To further elucidate our observations on the functional properties of this channel, we mutated seven lysines (Lys(48), Lys(161), Lys(165), Lys(170), Lys(248), Lys(250), and Lys(253)) to glutamic acid. The selected residues were previously shown to be accessible to chemical modification, and they map to three locations: loop 4 and loop 6, and within the barrel lumen. The seven mutant proteins were purified, and each was reconstituted into planar lipid bilayers to characterize its channel forming properties. The single substitution mutant porins displayed increased single channel conductances in 1 M KCl ranging between 134 and 178% of the single channel conductance for wild-type Hib porin. Six of the seven mutant porins also displayed altered current-voltage relationships when compared to wild-type Hib porin. Whereas Lys(170)Glu had activity similar to wild-type Hib porin, Lys(48)Glu, Lys(248)Glu, and Lys(253)Glu showed substantial voltage gating at both positive and negative polarities. Lys(161)Glu and Lys(250)Glu gated only at negative potentials, and Lys(165)Glu gated only at positive potentials. Rather than ascribing one specific loop in gating, our analyses of these mutant Hib porins suggest that voltage gating can be attributed to contributions from loops 4 and 6 and a residue within the barrel lumen.


Risk of contracting SARS-CoV-2 (COVID-19) from hospital admission and the impact of protection efforts on acute stroke treatment.
It is unclear how interventions designed to restrict community and in-hospital exposure to the SARS-CoV-2 (COVID-19) virus influenced stroke care for patients seeking acute treatment. Therefore, we aimed to determine how these COVID-19 interventions impacted acute stroke treatment times and to assess the risk of contracting COVID-19 due to their stay in our medical center. Retrospective, single center, two-phase study evaluating hospital and community trends from 12/2019 - 04/2020 compared to the previous year and pre/post (n = 156/93) intervention implementation. Phase I assessed stroke treatment times, delay to hospital arrival, and witnessed stroke volume. Phase II, a post-implementation telephone survey, assessed risk of developing symptoms or testing positive for COVID-19. Stroke volume declined by 29% (p < .05) from April to March compared to the previous year. However, no significant delays in seeking medical care (pre Mdn=112, post Mdn=95, p = .34) was observed. Witnessed stroke volume decreased 11% (p < .001) compared to the pre-implementation group, but no significant delay in IV alteplase (pre Mdn=22 mins; post Mdn=26 mins, p = .08) nor endovascular treatment (pre Mdn=60 mins; post Mdn=80 mins, p = .45) was observed. In Phase II, 63 patients participated, two tested (3%) COVID-19 positive during admission and four (6%) within two weeks of discharge. COVID-19 contraction risk during and after hospitalization remained similar to the general population (RR=1.75, 95%CI: 0.79-3.63). Overall results indicated a marked decrease in stroke volume, no significant delays to either seek or provide acute stroke care were evident, and COVID-19 contraction risk was low. Seeking acute stroke medical care outweighs the risk of COVID-19 exposure.


Agreement and reliability of pelvic floor measurements during contraction using three-dimensional pelvic floor ultrasound and virtual reality.
Virtual reality is a novel method of visualizing ultrasound data with the perception of depth and offers possibilities for measuring non-planar structures. The levator ani hiatus has both convex and concave aspects. The aim of this study was to compare levator ani hiatus volume measurements obtained with conventional three-dimensional (3D) ultrasound and with a virtual reality measurement technique and to establish their reliability and agreement. 100 symptomatic patients visiting a tertiary pelvic floor clinic with a normal intact levator ani muscle diagnosed on translabial ultrasound were selected. Datasets were analyzed using a rendered volume with a slice thickness of 1.5 cm at the level of minimal hiatal dimensions during contraction. The levator area (in cm(2)) was measured and multiplied by 1.5 to get the levator ani hiatus volume in conventional 3D ultrasound (in cm(3)). Levator ani hiatus volume measurements were then measured semi-automatically in virtual reality (cm(3) ) using a segmentation algorithm. An intra- and interobserver analysis of reliability and agreement was performed in 20 randomly chosen patients. The mean difference between levator ani hiatus volume measurements performed using conventional 3D ultrasound and virtual reality was 0.10 (95% CI, - 0.15 to 0.35) cm(3). The intraclass correlation coefficient (ICC) comparing conventional 3D ultrasound with virtual reality measurements was > 0.96. Intra- and interobserver ICCs for conventional 3D ultrasound measurements were > 0.94 and for virtual reality measurements were > 0.97, indicating good reliability for both. Levator ani hiatus volume measurements performed using virtual reality were reliable and the results were similar to those obtained with conventional 3D ultrasonography.


Monoamine Oxidase Inhibitors Prevent Glucose-Dependent Energy Production, Proliferation and Migration of Bladder Carcinoma Cells.
Bladder cancer is the 10th most common cancer in the world and has a high risk of recurrence and metastasis. In order to sustain high energetic needs, cancer cells undergo complex metabolic adaptations, such as a switch toward aerobic glycolysis, that can be exploited therapeutically. Reactive oxygen species (ROS) act as key regulators of cancer metabolic reprogramming and tumorigenesis, but the sources of ROS remain unidentified. Monoamine oxidases (MAOs) are mitochondrial enzymes that generate H2O2 during the breakdown of catecholamines and serotonin. These enzymes are particularly important in neurological disorders, but recently, a new link between MAOs and cancer has been uncovered, involving their production of ROS. At present, the putative role of MAOs in bladder cancer has never been evaluated. We observed that human urothelial tumor explants and the bladder cancer cell line AY27 expressed both MAO-A and MAO-B isoforms. Selective inhibition of MAO-A or MAO-B limited mitochondrial ROS accumulation, cell cycle progression and proliferation of bladder cancer cells, while only MAO-A inhibition prevented cell motility. To test whether ROS contributed to MAO-induced tumorigenesis, we used a mutated form of MAO-A which was unable to produce H2O2. Adenoviral transduction of the WT MAO-A stimulated the proliferation and migration of AY27 cells while the Lys305Met MAO-A mutant was inactive. This was consistent with the fact that the antioxidant Trolox strongly impaired proliferation and cell cycle progression. Most interestingly, AY27 cells were highly dependent on glucose metabolism to sustain their growth, and MAO inhibitors potently reduced glycolysis and oxidative phosphorylation, due to pyruvate depletion. Accordingly, MAO inhibitors decreased the expression of proteins involved in glucose transport (GLUT1) and transformation (HK2). In conclusion, urothelial cancer cells are characterized by a metabolic shift toward glucose-dependent metabolism, which is important for cell growth and is under the regulation of MAO-dependent oxidative stress.


Effects of COX inhibition and LPS on formalin induced pain in the infant rat.
In the adult, immune and neural processes jointly modulate pain. During development, both are in transition and little is known about the role that the immune system plays in pain processing in infants and children. The objective of this study was to determine if inhibition or augmentation of the immune system would alter pain processing in the infant rat, as it does in the adult. In Experiment 1, rat pups aged 3, 10, or 21 (PN3, PN10, and PN21) days of age were pretreated with NS398 (selective cyclooxygenase (COX)-2 inhibitor) or SC560 (selective COX-1 inhibitor) and tested in the intraplantar formalin test to assess effects of COX inhibition on nociception. Neither drug had an effect on the behavioral response at PN3 or PN10 pups but both drugs attenuated nociceptive scores in PN21 pups. cFos expression in the spinal cord likewise was reduced only at PN21. In Experiment 2, pups were injected with lipopolysaccharide (LPS) prior to the formalin test at PN3 or PN21. LPS increased the nociceptive response more robustly at PN21 than at PN3, while increasing cytokine mRNA equally at both ages. The augmentation of pain responding at PN21 was largely during the late stages of the formalin test, as reported in the adult. These data support previous findings demonstrating late maturing immune modulation of nociceptive behaviors.


Crystal structure of monofunctional histidinol phosphate phosphatase from Thermus thermophilus HB8.
Monofunctional histidinol phosphate phosphatase from Thermus thermophilus HB8, which catalyzes the dephosphorylation of l-histidinol phosphate, belongs to the PHP family, together with the PHP domain of bacterial DNA polymerase III and family X DNA polymerase. We have determined the structures of the complex with a sulfate ion, the complex with a phosphate ion, and the unliganded form at 1.6, 2.1, and 1.8 A resolution, respectively. The enzyme exists as a tetramer, and the subunit consists of a distorted (betaalpha)7 barrel with one linker and one C-terminal tail. Three metal sites located on the C-terminal side of the barrel are occupied by Fe1, Fe2, and Zn ions, respectively, forming a trinuclear metal center liganded by seven histidines, one aspartate, one glutamate, and one hydroxide with two Fe ions bridged by the hydroxide. In the complexes, the sulfate or phosphate ion is coordinated to three metal ions, resulting in octahedral, trigonal bipyramidal, and tetrahedral geometries around the Fe1, Fe2, and Zn ions, respectively. The ligand residues are derived from the four motifs that characterize the PHP family and from two motifs conserved in histidinol phosphate phosphatases. The (betaalpha)7 barrel and the metal cluster are closely related in nature and architecture to the (betaalpha)8 barrel and the mononuclear or dinuclear metal center in the amidohydrolase superfamily, respectively. The coordination behavior of the phosphate ion toward the metal center supports the mechanism in which the bridging hydroxide makes a direct attack on the substrate phosphate tridentately bound to the two Fe ions and Zn ion to hydrolyze the phosphoester bond.


Factorial validity and internal reliability of Honey and Mumford's Learning Styles Questionnaire.
Honey and Mumford's Learning Styles Questionnaire was derived from the same conceptual basis as Kolb's Learning Style Inventory and may provide a more reliable and valid measure of Kolb's learning style constructs. The Learning Styles Questionnaire has not been psychometrically evaluated as extensively as the Learning Style Inventory. Since there is no published information on how the Learning Styles Questionnaire scales were derived, an attempt was made to factor analyze the responses to the questionnaire. Confirmatory factor analysis of 284 psychology undergraduates' responses identified a four-factor oblimin solution as the most satisfactory model investigated. Implications for interpretation and use within higher education are discussed.


Collagen-coated polylactide microcarriers/chitosan hydrogel composite: injectable scaffold for cartilage regeneration.
A novel structure of injectable scaffold is designed and fabricated by combining collagen-coated polylactide (PLA) microcarriers and crosslinkable chitosan hydrogel. The collagen-coated PLA microcarriers were firstly mixed with the hydrogel precursor, a thickening agent of konjac glucomannan (KGM), and redox initiators of ammonium persulfate and tetramethylethylenediamine (TMEDA). The mixture was then injected into a mold and incubated at 37 degrees C to obtain the composite scaffold. The hydrogel can deliver the collagen-coated PLA microcarriers to the desired site and, after gelation, will prevent them from uncontrolled movement. On the other hand, the collagen-coated PLA microcarriers can substantially enhance the mechanical properties of the composite system. It was found that the microcarriers suspended stably in 0.6% KGM/1% chitosan derivative (CML) solution at 37 degrees C at least for 15 min. The dynamic elastic modulus (G') of the composite scaffold increased along with the increase of the microcarrier content. G' of the composite scaffold with 10% microcarriers was measured as 0.87-2.15 MPa at a frequency range of 0.1-100 rad/s, which was 120-90 times higher than that of its hydrogel system alone (12.1-24.4 kPa). In vitro culture of chondrocytes/composite scaffold showed that the cell metabolic activity increased rapidly before day 9, then leveled off. Cells in the hydrogel could attach and grow on the surface of the collagen-coated PLA microcarriers to form confluent cell layers after days 9-12. These features make the composite scaffold to be injectable and applicable in either tissue engineering, or regenerative medicine, and in particular, in orthopaedics.


Cerebral artery dilation during transient ischemia is impaired by amyloid β deposition around the cerebral artery in Alzheimer's disease model mice.
Transient ischemia is an exacerbation factor of Alzheimer's disease (AD). We aimed to examine the influence of amyloid β (Aβ) deposition around the cerebral (pial) artery in terms of diameter changes in the cerebral artery during transient ischemia in AD model mice (APPNL-G-F) under urethane anesthesia. Cerebral vasculature and Aβ deposition were examined using two-photon microscopy. Cerebral ischemia was induced by transient occlusion of the unilateral common carotid artery. The diameter of the pial artery was quantitatively measured. In wild-type mice, the diameter of arteries increased during occlusion and returned to their basal diameter after re-opening. In AD model mice, the artery response during occlusion differed depending on Aβ deposition sites. Arterial diameter changes at non-Aβ deposition site were similar to those in wild-type mice, whereas they were significantly smaller at Aβ deposition site. The results suggest that cerebral artery changes during ischemia are impaired by Aβ deposition.


Chemical, pharmacological, and biological characterization of the culinary-medicinal honey mushroom, Armillaria mellea (Vahl) P. Kumm. (Agaricomycetideae): a review.
Recently, studies have been conducted on the chemical composition of fruiting bodies of the culinary-medicinal Honey mushroom, Armillaria mellea (Vahl.) P. Kumm. (higher Basidiomycetes). It is considered in Europe and Asia as edible and medicinal, when appropriately prepared, and has demonstrated the presence of different groups of organic compounds, including carbohydrates, sterols, sphingolipids, fatty acids, sesquiterpenes, non-hallucinogenic indole compounds, peptides, enzymes, adenosine derivatives, and many other components. Most of these metabolite groups possess potential therapeutic and dietary values. The results of quantitative analyses of indole compounds and heavy metals signal potential health hazards for humans. Some of the studies reviewed herein describe in detail the mechanism of symbiosis between A. mellea and the orchid species Gastrodia elata. This orchid is native to Asia, Australia, and New Zealand, and is used in therapeutics in official Chinese medicine.


Is perfection ever attainable? Strong coupling effects in the Perfect Echo.
The Perfect Echo sequence, originally proposed in the late 1980s, has recently been popularised with many applications in the field of small-molecule proton NMR spectroscopy. The Perfect Echo refocuses all homonuclear J-couplings for AX spin systems and refocuses magnetization in-phase for more complex weakly coupled spin systems, albeit with some intensity reduction. In contrast to suggestions in previous publications, spectra acquired in our laboratory showed that the Perfect Echo caused intensity distortions in strongly coupled systems where the chemical shift difference between the coupled spins was not large compared to the J-coupling. This paper reports experimental observations and theoretical analysis of strongly coupled spins to confirm the distortions are real and that they originate principally from transfer of magnetization caused by the final inversion pulse of the Perfect Echo. The intensity changes are not large, but because of them, identifications of coupling partners based on resonance intensities ("roofing") can no longer be relied on when the Perfect Echo is used. However, theory and experiment confirm that adding an orthogonal excitation pulse at the end of the Perfect Echo greatly reduces the distortions.


A process evaluation of 'We Can Quit': a community-based smoking cessation intervention targeting women from areas of socio-disadvantage in Ireland.
Smoking poses a serious risk of early preventable death and disease especially for women living with socio-economic disadvantage (SED). A smoking cessation programme, 'We Can Quit', was developed in Ireland tailored to SED women. This includes group-based support delivered by trained lay local community facilitators (CFs) and free nicotine replacement therapy (NRT). The intervention was pilot tested in a cluster randomised controlled trial, 'We Can Quit 2'. This paper reports on the WCQ2 process evaluation which assessed feasibility and acceptability of the programme and trial processes. Embedded qualitative design using the UK Medical Research Council's process evaluation framework. Semi-structured interviews with trial participants (N = 21) and CFs (N = 8). Thematic analysis was utilised. Peer-modelling, a non-judgemental environment, CFs facilitation of group support were viewed as acceptable programme related factors. Some participants expressed concerns about NRT side effects. Provision of free NRT was welcomed and accepted by participants, although structural barriers made access challenging. Pharmacists took on a role that became larger than originally envisaged - and the majority provided additional support to women in their quit attempts between group meetings which augmented and supplemented the intervention sessions provided by the CFs. Participants reported good acceptance of repeated measures for data collection, but mixed acceptability of provision of saliva samples. Low literacy affected the feasibility of some women to fully engage with programme and trial-related materials. This was despite efforts made by intervention developers and the trial team to make materials (e.g., participant intervention booklet; consent forms and participant information leaflets) accessible while also meeting requirements under 2018 European General Data Protection Regulation legislation. Hypothetical scenarios of direct (e.g., researcher present during programme delivery) and indirect (e.g., audio recordings of programme sessions) observational fidelity assessments for a future definitive trial (DT) were acceptable. Intervention and trial-related processes were generally feasible and acceptable to participants and CFs. Any future DT will need to take further steps to mitigate structural barriers to accessing free NRT; and the established problem of low literacy and low educational attainment in SED areas, while continuing to comply within the contemporary legislative research environment. WCQ2 pilot trial ( ISRCTN74721694 ).


Human RNA polymerase I-driven reverse genetics for influenza a virus in canine cells.
We have established a human RNA polymerase I (pol I)-driven influenza virus reverse genetics (RG) system in the Madin-Darby canine kidney 33016-PF cell line, which is approved for influenza vaccine manufacture. RNA pol I polymerases are generally active only in cells of species closely related to the species of origin of the polymerases. Nevertheless, we show that a nonendogenous RNA pol I promoter drives efficient rescue of influenza A viruses in a canine cell line. Application of this system allows efficient generation of virus strains and presents an alternative approach for influenza vaccine production.


Serendipitous Treatment of Tularemia in Pregnancy.
We present a young pregnant woman who developed ulceroglandular tularaemia following a bite wound from a kitten. She grew Francisella tularensis from the ulcer. While awaiting bacterial culture results and serology for Bartonella, she was treated with azithromycin, with resolution of fever and axillary tenderness. Treatment recommendations for tularemia are either gentamicin or doxycycline, both of which can be perilous to the fetus. A Centers for Disease Control and Prevention report on the macrolide susceptibility of North American isolates of this organism has been underappreciated. The unanticipated result from this patient may give another potential option for treatment of tularemia in pregnancy.


Cisplatin and etoposide chemotherapy combined with early concurrent twice-daily thoracic radiotherapy for limited-disease small cell lung cancer in elderly patients.
The optimal management of elderly patients with limited-disease small cell lung cancer (LD-SCLC) has not been established. The records of elderly (>or=70 years of age) patients with LD-SCLC who had been treated with etoposide and cisplatin chemotherapy with early concurrent twice-daily thoracic radiotherapy (TRT) were reviewed retrospectively. Of the 25 elderly patients with LD-SCLC identified, 12 (48%) individuals received etoposide-cisplatin chemotherapy with early concurrent twice-daily TRT. The main toxicities of this treatment regimen were hematologic, with neutropenia of Grade 4 being observed in all patients and febrile neutropenia of Grade 3 in eight patients during the first cycle of chemoradiotherapy. The toxicity of TRT was acceptable, with all patients completing the planned radiotherapy within a median of 29 days (range, 19-33). No treatment-related deaths were observed. The median progression-free survival and overall survival times were 14.2 months (95% confidence interval, 4.3-18.2) and 24.1 months (95% confidence interval, 11.3-27.2), respectively. Etoposide-cisplatin chemotherapy with early concurrent twice-daily TRT was highly myelotoxic in elderly patients with LD-SCLC, although no treatment-related deaths were observed in our cohort. Prospective studies are required to establish the optimal schedule and dose of chemotherapy and TRT in such patients.


Oral health status of pregnant women in the Republic of Kiribati.
Prenatal dental examinations were performed from June 2012 to May 2013 in the Republic of Kiribati as a Japan International Cooperation Agency support program. We analyzed the examination data and compared it with Japanese data retrospectively to clarify the oral health condition of pregnant women in the Republic of Kiribati. We recorded the DMF index, gingival status, and calculus attachment, analyzed data of 512 pregnant women. We also compared the city and the rural group data. The average number of present teeth, decayed teeth, missing teeth and filled teeth was 26.9, 2.5, 1.1, 0.2, respectively. Pregnant Kiribati women had significantly more decayed teeth and fewer filled teeth, more severe periodontal condition, more calculus deposition, and more severe gingival swelling than pregnant Japanese women. No significant difference was found in missing and filled teeth, but pregnant women in the city group had significantly more decayed teeth and tooth stumps than those in the rural group. Our findings indicate that pregnant women in Kiribati have more decayed teeth, more missing teeth, fewer filled teeth, and more severe periodontal problems than their counterparts in Japan. Additionally, the oral health status of pregnant women in Kiribati could be subject to regional variations. J. Med. Invest. 70 : 110-114, February, 2023.


Two novel mitochondrial and chloroplastic targeting-peptide-degrading peptidasomes in A. thaliana, AtPreP1 and AtPreP2.
Two novel metalloendopeptidases in Arabidopsis thaliana, AtPreP1 and AtPreP2, are responsible for the degradation of targeting peptides in mitochondria and chloroplasts. Both AtPreP1 and AtPreP2 contain ambiguous targeting peptides and are dually targeted to both organelles. The proteases also have the capacity to degrade unstructured peptides of up to 65 amino acid residues, but not small proteins. The catalysis occurs in a huge catalytic chamber revealed by the crystal structure of AtPreP1 at 2.1 A. The enzymes show a preference for basic and small uncharged amino acids or serines at the cleavage sites. Despite similarities in cleavage specificities, cleavage-site recognition differs for both proteases and is context- and structure-dependent. The AtPreP1 and AtPreP2 genes are differentially expressed in Arabidopsis.


[Changes in compliance of the intact thorax under rising insufflation pressure and the limits of physiological elasticity: studies on guinea pigs].
Pressure-volume curves of 26 guinea pigs, weighing 124 and 1135 grams were recorded; the curves being achieved by a gradual inflation of the lungs in the intact thorax. The presentation of the compliance alteration as a function of insufflation pressure (IFP) shows a uniform inflation characteristic, independent of body weight: the high level of compliance at the beginning of the curve starts to decrease at an IFP value of 0/76 kPa and falls gradually to approximately a third of the starting value, yet at an IFP value of 1.9 kPa the curve rises sharply again. Complete pressure-volume loops of 8 guinea pigs, achieved by inflating, relaxing and re-inflating the lungs, were also recorded. Where the IFP value was less than 1.9 kPa the inflation curves were identical. Where the IFP value, however, was greater than 1.9 kPa the adaptation phenomenon described by BERNSTEIN [6] with increasing hysteresis and "air trapping" appeared. One may conclude, therefore, that with an IFP value of 1.9 kPa the limit of the physiological expansion of the guinea pigs' lungs is reached.


White-coat effect in normotension and hypertension.
The difference between clinic and daytime ambulatory blood pressure is referred to as the white-coat effect. In this study, we investigated (i) the magnitude of the white-coat effect in subjects with different daytime ambulatory blood pressure levels, and (ii) the association of the white-coat effect with left ventricular mass. A total of 1581 subjects underwent clinic blood pressure readings, 24-h ambulatory blood pressure monitoring and left ventricular echocardiographic assessment. Their mean daytime systolic blood pressure varied from 88.0 to 208.9 mmHg and their mean daytime diastolic blood pressure from 40.3 to 133.0 mmHg. A negative correlation was found between the systolic or diastolic white-coat effect and the systolic or diastolic daytime ambulatory blood pressure (r = -0.22, P < 0.000 and r = -0.50, P < 0.000, respectively). Left ventricular mass significantly correlated with ambulatory blood pressure (P < 0.001), but there was no association between left ventricular mass and clinic blood pressure or white-coat effect. Furthermore, the white-coat effect was reversed at the highest level of systolic or diastolic daytime ambulatory blood pressure (systolic over 170 mmHg or diastolic over 100 mmHg) when systolic or diastolic daytime ambulatory blood pressure was higher than systolic or diastolic clinic blood pressure (ambulatory blood pressure hypertension). The white-coat effect shows an inverse association with daytime ambulatory blood pressure level (systolic or diastolic), being significantly more prominent for levels below 140/80 mmHg for systolic/diastolic daytime ambulatory blood pressure and reversed with daytime ambulatory blood pressure levels above 170/100 mmHg.


A systems approach to error prevention in medicine.
Minimization of medical errors is at the core of all clinical medical practices. The first tenet of care is to do no harm. The enormous complexity of modern medical care has made error detection and management extremely difficult. Traditional deterministic methods of solving the "error issue" cannot cope with the huge number of potential errors that are possible. Systems thinking and approach to error reduction provides a different avenue for tackling this challenging dilemma. The intent of this article is to introduce a systems view of medical errors and to explain how it can provide new insights about dealing with massively complex organizations such as the healthcare system. Important features include an understanding of system relationships, sources of error, human components, optimization versus perfection in systems and the interrelationships between human and system processes.


[Treatment of preretinal retrohyaloidal hemorrhage: value of early argon laser photocoagulation].
Within the first three or four days after occurrence of a premacular subhyaloidal hemorrhage, the posterior vitreous boundary layer may be lacerated by argon laser coagulation in such a way that the blood flows into the vitreous body, where it is absorbed within a few weeks. Older premacular hemorrhages under an intact vitreous boundary layer, typically green-white in color, have to be treated by more invasive vitreosurgical procedures.


Towards the control of a powered orthosis for people with muscular dystrophy.
The paper describes the development of a passive/active orthosis for people with limited anti-gravity strength in their arms. This is symptomatic of conditions such as muscular dystrophy and spinal muscular atrophy. A passive orthosis was designed and developed using linear elastic elements. The system is being tested with children with disabilities and preliminary results are encouraging. An RT200 robot was also used as a test-bed for an active orthosis. The robot was instrumented with a six-axis force/torque sensor at the end-effector. The force acted as the input to the robot. The robot kinematics and dynamics were modelled. A number of control schemes were implemented on the test-bed including force proportional to velocity and acceleration; these schemes were evaluated with two subjects.


Oxygen reduction on silver low-index single-crystal surfaces in alkaline solution: rotating ring disk(Ag(hkl)) studies.
The rotating ring disk method is applied to investigate the oxygen reduction reaction on Ag single-crystal surfaces in alkaline solution over the temperature range 293-333 K. At all temperatures, the oxygen reduction reaction proceeds through the 4e- reaction pathway with a very small (approximately 0.5-2%) peroxide formation. At the same temperature and overpotentials, the kinetics of the ORR always increases in the order (100) < or = (111) < (110), indicating that the reaction is structure-sensitive. We present an interpretation of the structure sensitivity based on the supposition that it arises from (i) a potential-dependent adsorption of spectator hydroxyl ions and (ii) variations in activation energies, which are determined by the O2 adsorption on Ag single-crystal surfaces covered by adsorbed oxygenated species.


Investigation of rice performance characteristics: A comparative study of LR, ANN, and RSM.
Parboiling is a type of heat pretreatment used in rice processing to reach higher head rice yield and improve the nutrition properties of raw rice. In this research, the goals were prediction and determination of optimum conditions for parboiled rice processing using the response surface method (RSM) as well as modeling the output values by linear regression (LR) and artificial neural networks (ANN). The parameters including steaming time (0, 5, 10, and 15 min), dryer type (solar and continuous dryers), and drying air temperature (35, 40, and 45°C) were employed as input values. In addition, the breakage resistance (BR) and head rice yield (HRY) were selected as output values. The ANN-based nonlinear regression, the multi-layer perceptron (MLP), and the radial basis function (RBF) have been developed to model the process parameters, as well as the central composite design (CCD) was conducted for optimization of BR and HRY values. The outputs of RBF network have been successfully applied to predict higher coefficient of determination of BR and HRY as 0.989 and 0.986, respectively, indicating the appropriateness of the model equation in predicting head rice yield and breakage resistance when the three processing variables (steaming time, dryer type, and drying air temperature) are mathematically combined. Also, the lower root mean square error (RMSE) was obtained for each one as 0.043 and 0.041. The optimum values of BR and HRY were obtained as 12.80 N and 67.3%, respectively, at 9.62 min and 36.9°C for a solar dryer with a desirability of 0.941. In addition, the same values were obtained as 14.50 N and 72.1%, respectively, at 8.77 min and 37.0°C for a continuous dryer with a desirability of 0.971.


[Wernekink Commissure Syndrome With Hallucinations and Involuntary Groping:Report of One Case].
Wernekink commissure syndrome is a rare midbrain syndrome with bilateral cerebellar dysfunction,eye movement disorder,and palatal myoclonus.Few cases of this syndrome have been reported in China,let alone those combined with hallucinations and involuntary groping.This paper reports the diagnosis and treatment of a case of Wernekink commissure syndrome with hallucinations and involuntary groping,aiming to enrich the knowledge about this disease for clinicians.


Multi-informant Assessment of Internalizing Concerns: Rater Concordance and Implications for Decision-Making.
Rising rates of mental health challenges among youths have become a significant concern following the COVID 19 pandemic. Although strong evidence supports the implementation of universal screening as a preventative approach to address unmet mental health concerns, the research is less clear surrounding the use of such data in decision-making processes when significant discrepancies between informants (e.g., students and teachers) exist. The purpose of the study was twofold. First, the study aimed to determine the degree of rater concordance between teachers and students on students' internalizing concerns. The second objective was to determine whether concordance on internalizing behaviors differs across ages/grades and if this differentially impacts distal (i.e., academic) outcomes. Results indicated that teachers and students demonstrated limited agreement on ratings of internalizing behaviors. However, when students and teachers agreed, higher and more positive emotional behaviors were linked to higher reading/math performance. Furthermore, patterns of informant dis/agreement and relationships between internalizing concerns and academic outcomes were similar across grade levels. Implications and areas for future research are discussed.


Development of quantitative duplex real-time PCR method for screening analysis of genetically modified maize.
A duplex real-time PCR method was developed for quantitative screening analysis of GM maize. The duplex real-time PCR simultaneously detected two GM-specific segments, namely the cauliflower mosaic virus (CaMV) 35S promoter (P35S) segment and an event-specific segment for GA21 maize which does not contain P35S. Calibration was performed with a plasmid calibrant specially designed for the duplex PCR. The result of an in-house evaluation suggested that the analytical precision of the developed method was almost equivalent to those of simplex real-time PCR methods, which have been adopted as ISO standard methods for the analysis of GMOs in foodstuffs and have also been employed for the analysis of GMOs in Japan. In addition, this method will reduce both the cost and time requirement of routine GMO analysis by half. The high analytical performance demonstrated in the current study would be useful for the quantitative screening analysis of GM maize. We believe the developed method will be useful for practical screening analysis of GM maize, although interlaboratory collaborative studies should be conducted to confirm this.