Normal aortic dimensions and flow in 168 children and young adults.
Knowledge of normal aortic dimensions is important while evaluating children with aortic root dilatation. The purpose of the study was to create normal values for aortic dimensions with two-dimensional echocardiography and for aortic flow velocities with Doppler echocardiography in healthy children and young adults. One hundred and sixty-eight healthy children were studied by a single observer using digitized two-dimensional (2DE) and Doppler echocardiography. The 2DE measurements were obtained at the level of aortic annulus, sinus, sinotubular junction, before the origin of innominate artery, before and after the origin of left carotid artery, after left subclavian artery and descending aorta at the level of the diaphragm. Doppler measurements were made from ascending aorta and from descending aorta. For the analysis the subjects were divided into five groups according to body surface area (BSA): 0.5-0.75 m2, 0.75-1.0 m2, 1.0-1.25 m2, 1.25-1.5 m2 and over 1.5 m2. Aortic dimensions normalized to BSA were greater in smaller children at all levels. All diameters correlated closely with age, BSA, height and weight (for each r>0.75, P<0.001). The best predictor of aortic dimensions was BSA with r values over 0.84 for all estimates (P<0.001). The diameters of ascending and descending aorta were similar in both genders when indexed to BSA. Flow velocities in descending aorta were greater than those measured in ascending aorta (P<0.001 for all measurements). There were significant inverse correlations with heart rate and velocity time integral in ascending and descending aorta (r=-0.32 and -0.53, P<0.001, respectively). The presented aortic dimensions at eight levels from the valve annulus to the descending thoracic aorta by 2DE in conjunction with Doppler measurements of ascending and descending aorta in 168 healthy subjects will serve as reference data for further studies and clinical use in patients with various cardiac abnormalities.


Reduced pulmonary metabolism of endothelin-1 in canine tachycardia-induced heart failure.
Plasma endothelin-1 (ET-1) increases in congestive heart failure (CHF). The pulmonary vascular bed could contribute to this increase through a reduced clearance. We evaluated the effect of tachycardia-induced CHF on pulmonary ET-1 kinetics. To discern between changes due to variations in pulmonary hemodynamics from true alterations of endothelial cell functions, we quantified ET-1 kinetics in isolated rat lungs under variable pressure and flow-rate conditions. Indicator-dilution studies were performed in anesthetized dogs (n = 14) before and 3 weeks after rapid ventricular pacing and in isolated lungs from healthy rats (n = 4). In isolated lungs, graded increases in perfusion rate from 5-25 ml/min caused gradual reductions in ET-1 extraction from 60 +/- 1.5% to 17 +/- 4.9% (mean +/- S.D.). The capacity to clear ET-1 from the circulation, as computed from the permeability-surface area product (PS), however did not vary over this range of flows. CHF increased plasma ET-1 (11.2 +/- 11.4 vs. 5.2 +/- 1.6 fmol/ml, p < 0.01), did not affect pulmonary ET-1 extraction (29.4 +/- 12.5% vs. 29.9 +/- 12.9%), but decreased the PS (8.3 +/- 5.4 cm3/s vs. 14.4 +/- 9.9 cm3/s, p = 0.038). Contrary to the invariability of the PS in normal isolated rat lungs, CHF was associated with a positive relationship between the PS and pulmonary plasma flow (r = 0.65, p < 0.01). ET-1 binding studies in lung tissues showed no significant variations in ETA and ETB receptors densities but revealed a threefold decrease in binding affinity (p < 0.01) that may explain the reduced clearance. CHF causes a reduction of pulmonary ET-1 clearance that likely contributes to the increased circulating ET-1 levels and reflects pulmonary metabolic dysfunction associated with this condition.


Computed tomographic morphometry of thoracic pedicles: safety pedicle parameter measurement of the Chinese immature thoracic spine.
Our objective was to quantify the morphometric characteristics of the pedicles of the Chinese immature thoracic spine. A total of 120 patients aged 5-14 years underwent standard thoracic computed tomography (CT). The patients were grouped according to age: group 1 (5-8 years of age), group 2 (9-11 years of age) and group 3 (12-14 years of age). Images were reformatted, and multiplanar reconstructions were used to attain images of thoracic pedicles on sagittal, coronal and transverse planes. The measurements included the inner and outer pedicle diameters on the transverse plane, pedicle sagittal diameter, pedicle length and the pedicle angle on the transverse. (1) Pedicle diameters on the transverse plane decreased gradually from T1 to T4 and increased gradually from T5 to T12. The shortest transverse diameter of the thoracic pedicle was T4 or T5. (2) The sagittal diameter was significantly larger than the transverse diameter except at T1. (3) The length of the pedicle from the posterior cortex to the anterior cortex of the vertebra increased from T1 to T12. (4) The pedicle angle decreased gradually from T1 to T8 and became negative below the level of T10. The length of the pedicle changed with age significantly, but the pedicle angle changed with age insignificantly. The success of transpedicular fixation requires a better understanding of morphological features at different ages and reasonable selection of the diameter, length and direction of the pedicle screws based on X-ray and CT films.


Isolation and molecular characterization of extended spectrum beta lactamase producing Escherichia coli from chicken meat in Pakistan.
The goal of this study was to find E. coli, a prevalent pathogen that causes food-borne illnesses, in chicken samples (n = 500) collected from three districts in KhyberPukhtunkhwa: Mardan, Swabi, and Swat. The E. coli isolates were identified by Gram staining, API strips and Universal Stress Protein. A total of 412 samples tested positive for E. coli and were sensitive to MEM, TZP, and FOS as evidenced by disc diffusion method. The isolates were resistant to TE, NOR, and NA with statistically significant results (P≤0.05). The isolates showed the presence of different antibiotic resistance genes; blaOXA-1, blaCTX-M15, blaTEM-1, QnrS, TetA, AAC, AAD, Sul1 and Sul2. The results revealed mutations in blaOXA-1 gene (H81Q), blaTEM-1 (C108Y, T214A, K284E and P301S), QnrS (H95R) and Sul2 (E66A). The findings of this study may be helpful in better management of E. coli infections by physicians.


A point mutation, C to T, in exon 8 of the porphobilinogen deaminase gene in a Japanese family with acute intermittent porphyria.
Acute intermittent porphyria (AIP) is an autosomal dominant disease characterized by a deficiency of porphobilinogen deaminase (PBGD). To date, only two mutations have been reported in Japanese patients. We report here another mutation of the gene in a Japanese patient. Analysis of the PCR amplified DNA fragments of the gene by direct-sequencing method revealed the gene abnormality responsible for the disease. The mutation found was a point mutation, C to T, in exon 8 of the gene at position 346 of the housekeeping cDNA from the translation codon ATG. This mutation resulted in an Arg116 to Trp substitution. Four carriers in the family were successfully diagnosed by detecting the mutation using restriction analysis of PCR products.


Epigenetic regulation of MIR145 core promoter controls miR-143/145 cluster in bladder cancer progression and treatment outcome.
Owing to its highly heterogeneous molecular landscape, bladder cancer (BlCa) is still characterized by non-personalized treatment and lifelong surveillance. Motivated by our previous findings on miR-143/145 value in disease prognosis, we have studied the underlying epigenetic regulation of the miR-143/145 cluster in BlCa. Expression and DNA methylation of miR-143/145 cluster were analyzed in our screening (n = 162) and The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA; n = 412) cohorts. Survival analysis was performed using tumor relapse and progression as clinical endpoints for non-muscle-invasive bladder cancer (NMIBC; TaT1), while disease progression and patients' death were used for muscle-invasive bladder cancer (MIBC; T2-T4). TCGA-BLCA served as validation cohort. Bootstrap analysis was carried out for internal validation, while decision curve analysis was used to evaluate clinical benefit. TCGA-BLCA and screening cohorts highlighted MIR145 core promoter as the pivotal, epigenetic regulatory region on cluster's expression. Lower methylation of MIR145 core promoter was associated with aggressive disease phenotype, higher risk for NMIBC short-term progression, and poor MIBC survival. MIR145 methylation-fitted multivariate models with established disease markers clearly enhanced patients' risk stratification and prediction of treatment outcome. MIR145 core promoter methylation was identified as a potent epigenetic regulator of miR-143/145 cluster, supporting modern personalized risk stratification and management in BlCa.


Comparison of clinical and radiologic outcomes between non-operative and operative treatment in 5th metatarsal base fractures (Zone 1).
The treatment of Zone 1 fractures of the 5th metatarsal base with >2mm of displacement remains controversial. We prospectively analyzed 29 patients with 5th metatarsal base fractures (Zone 1) during 2009-2014. Radiography was performed to assess the degree of fracture gap and metatarsal length. Patients with gaps of 2mm or less were treated conservatively using a short leg cast or splint (Group A), while patients with fracture gap >2mm were randomly assigned to one of two groups. Group B patients were managed with open reduction and internal fixation (ORIF), and Group C patients were placed in a short leg cast only. Visual analog scale (VAS) score and American orthopedic foot and ankle society (AOFAS) score were obtained at the initial consult and at the last follow-up after treatment; change of the 5th metatarsal length was also measured at the initial consult and after complete bony union. Our study demonstrated that radiographic union of all cases was observed with a significant decrease in VAS and AOFAS scores, regardless of the initial fracture gap and type of management. Additionally, there was no difference seen in final VAS scores for patients with longer metatarsals when compared to those in whom the metatarsals were unchanged or shortened.


Association of early systolic blood pressure response to exercise with future cardiovascular events in patients with uncomplicated mild-to-moderate hypertension.
The relationship between blood pressure (BP) response during exercise and future cardiovascular events remains unclear. We assessed the association between an increase in early systolic BP (SBP) during exercise tests and future cardiovascular events in patients with sustained hypertension (sHT). Between 2002 and 2005, we enrolled 300 patients newly diagnosed with mild-to-moderate sHT without complications from the Asan Ambulatory Blood Pressure Monitoring registry. All the patients successfully performed treadmill tests, achieving target heart rate according to the Naughton/Balke protocol. The patients were divided into quartiles according to their SBP at 8 min (7.4 metabolic equivalent tasks). The primary outcome was the composite of all-cause death, new-onset ischemic heart disease and stroke. The 5-year survival rates did not differ significantly among quartiles 1-4 (100% vs. 96.6% vs. 94.4% vs. 98.3%, P=0.211). Relative to quartile 1, the 5-year event-free survival rates were significantly lower in patients in quartiles 3 (86.9% vs. 98.3%, P=0.023) and 4 (88.2% vs. 98.3%, P=0.023). After multivariable adjustment for covariates, the risk for the composite end point was higher for patients in quartiles 3 (Hazard ratio (HR) 4.69, 95% confidence interval (CI) 1.28-17.13, P=0.020) and 4 (HR 3.65, 95% CI 0.92-14.50, P=0.065) than in quartiles 1 and 2. Cardiovascular risk was significantly higher in patients with stage 4 SBP (>180 mm Hg) even after adjustment (HR 4.00, 95% CI 1.19-13.44, P=0.025). Increased submaximal SBP response to exercise may be a predictor of future cardiovascular events in patients with mild-to-moderate sHT.


[Student nurses and the notion of temporality].
Time is a key element of nursing. This is true for professional practice as well as for training. During practice placements, students discover the reality of a profession in which different temporalities come together, their own, as well as those of the patients and the institution. First year and third year students share their experience.


From single genes to co-expression networks: extracting knowledge from barley functional genomics.
The paper reports an 'in silico' approach to gene expression analysis based on a barley gene co-expression network resulting from the study of several publicly available cDNA libraries. The work is an application of Systems Biology to plant science: at the end of the computational step we identified groups of potentially related genes. The communities of co-expressed genes constructed from the network are remarkably characterized from the functional point of view, as shown by the statistical analysis of the Gene Ontology annotations of their members. Experimental, lab-based testing has been carried out to check the relationship between network and biological properties and to identify and suggest effective strategies of information extraction from the network-derived data.


Succinyl hydroxamates as potent and selective non-peptidic inhibitors of procollagen C-proteinase: design, synthesis, and evaluation as topically applied, dermal anti-scarring agents.
Succinyl hydroxamates 1 and 2 are disclosed as novel series of potent and selective inhibitors of procollagen C-proteinase (PCP) which may have potential as anti-fibrotic agents. Carboxamide 7 demonstrated good PCP inhibition and had excellent selectivity over MMPs involved in wound healing. In addition, 7 was effective in a cell-based model of collagen deposition (fibroplasia model) and was very effective at penetrating human skin in vitro. Compound 7 (UK-383,367) was selected as a candidate for evaluation in clinical studies as a topically applied, dermal anti-scarring agent.


Production of Artificially Doubly Glycosylated, 15N Labeled Prion Protein for NMR Studies Using a pH-Scanning Volatile Buffer System.
Bacterially expressed proteins used in NMR studies lack glycans, and proteins from other organisms are neither 15N labeled nor glycosylated homogeneously. Here, we add two artificial glycans to uniformly 15N labeled prion protein using a buffer system that evolves over a pH range to accommodate the conflicting pH requirements of the substrate and enzymes without the need to fine-tune buffer conditions. NMR and CD spectroscopy of the protein indicates that the glycans do not influence its fold.


High prevalence of TERT aberrations in myxoid liposarcoma: TERT reactivation may play a crucial role in tumorigenesis.
Myxoid liposarcoma (MLPS) is genetically characterized by FUS-DDIT3 or EWSR1-DDIT3 gene fusion and the high frequency of hotspot mutations (C228T or C250T) in the promoter region of telomerase reverse transcriptase (TERT) that encodes the TERT protein. The latter leads to telomerase reactivation, a mechanism of telomere maintenance. Although the TERT promoter hotspot mutation is a poor prognostic factor in various tumors, its effect on MLPS has not been reported in detail. In the present study, we examined the clinicopathological characteristics, prognosis, and telomere maintenance mechanisms in 83 primary tumor samples of MLPS, which were resected surgically at the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, from 2008 to 2020. TERT promoter hotspot mutations were observed in 77% (63/82) cases, and alternative lengthening of telomeres (ALT) was absent in all cases. Among the cases without TERT promoter hotspot mutations, TERT rearrangements, and minor point mutations in the TERT promoter region were found in 3 and 2 cases, respectively. TERT mRNA expression was observed consistently even in patients for whom no genomic TERT aberrations were detected, and the presence of TERT promoter hotspot mutation did not correlate significantly with either overall and metastasis-free survival (P = .56, P = .83, respectively) or clinicopathological features. Therefore, patients with MLPS characteristically shows TERT expression and a high prevalence of TERT aberrations. Our findings suggest that TERT aberration is not prognostic factor, but might occur at an early stage and play a key role in tumorigenesis.


Comparison of four populations of Acanthoscelides obtectus (Coleoptera: Bruchidae) from different Colombian ecosystems : Assay of Interpretation.
The bean weevil (Acanthoscelides obtectus) and its preferential host plant Phaseolus vulgaris probably originate from Central or South America. Acanthoscelides obtectus populations have developed for many years in varied and relatively isolated ecosystems in these regions. The influence of the host and of copulation on reproductive activity was studied in four Colombian insect populations from medium (2000 m) and low altitudes (1200 m). Most medium altitude strains of females do not produce oocytes in the absence of hosts or of copulation. These external stimuli can still influence oogenesis after a long period. Virgin females of low altitude strains produce oocytes early in imaginal life and oviposit rapidly in the presence of the host or after copulation. These characteristics can be maintained for many generations.The different strains react differently to a change of thermoperiod. It is suggested that the strain differences are related to the climatic and ecological conditions prevailing at the various altitudes in the Andes; differences are also apparently related to the reproductive cycle of the host plant, which is ingested by the larvae.


Differential expression of the regulator of G protein signaling RGS9 protein in nociceptive pathways of different age rats.
Regulators of G protein signaling (RGS) proteins are GTPase-activating proteins which act as modulators of G-protein-coupled receptors. RGS9 has two alternative splicing variants. RGS9-1 is expressed in the retina. RGS9-2 is expressed in the brain, especially abundant in the striatum. It is believed to be an essential regulatory component of dopamine and opioid signaling. In this study, we compared the expression of RGS9 proteins in the nervous system of different age groups of rats employing immunocytochemistry. In both 3-week- and 1-year-old rats, RGS9 is expressed abundantly in caudate-putamen, nucleus accumbens, and olfactory tubercle. It is also expressed abundantly in the ventral horn of the spinal cord and the dorsal root ganglion (DRG) cells. Quantitative analysis showed that the intensities of RGS9 expression in 1-year-old rats are higher than those in the 3-week-old rats in caudate-putamen, nucleus accumbens, olfactory tubercle, periaqueductal gray, and gray matter of the spinal cord. In contrast, in thalamic nuclei and locus coeruleus, the intensities of RGS9 immunostaining in 3-week-old rats are higher than in 1-year-old rats. In DRG cells, there is no significant difference between the two age groups. These data suggest that RGS9 is differentially expressed with age. Such differential expression may play an important role in neuronal differentiation and development as well as in neuronal function, such as dopamine and opioid signaling.


Independent predictors affecting the reduction of pediatric supracondylar humerus fractures: a retrospective cohort study.
Although it is important to understand the risk factors affecting the reduction of pediatric supracondylar humerus fractures (PSHFs), no inclusive study has been conducted so far. We performed a retrospective cohort study to identify the risk factors affecting the quality and difficulty of reduction for PSHFs. We reviewed 160 cases with a PSHF that had been surgically treated in our hospital between January 2007 and December 2019. We investigated age, sex, injured side, body mass index (BMI), modified Gartland classification, neurological deficit or an absent radial artery pulse at an initial examination, start time of the operation, waiting time from injury to surgery, operative time, reduction technique, and perioperative radiographic parameters. We calculated independent predictors of unsuccessful closed reduction, prolonged operative time, and malreduction using multivariate analyses. In a logistic regression analysis, modified Gartland type III was a significant predictor of unsuccessful closed reduction (OR 14.50 [95% CI 4.03-51.90]; P < 0.01) and BMI was a significant predictor of malrotation (OR 1.59 [95% CI 1.06-2.39]; P = 0.025). In a multiple linear regression analysis, BMI and open reduction were significant predictors of prolonged operative time (BMI, P = 0.011; open reduction, P < 0.01). If closed reduction fails, we should not hesitate to immediately switch to other methods. Obesity was an independent predictor of both prolonged operative time and malrotation, a finding that has not been previously reported. Rotational alignment should be carefully checked, especially for obese children, and accurately be reduced. Open reduction also extended operative time.


Synthesis and Characterization of a Novel Quaternary Ammonium Salt as a Corrosion Inhibitor for Oil-Well Acidizing Processes.
A quaternary ammonium salt, 1,1'-(1,4-phenylenebis(methylene))bis(4-formylpyridin-1-ium) (PMBF), was synthesized, characterized, and investigated as an inhibitor for C1018 (type steel in oil wells) corrosion in 17.5% HCl solution. The chemical structure of PMBF was confirmed using altered techniques. Potentiodynamic polarization (PDP) was employed to investigate the corrosion inhibition effect of the synthesized compound in a 17.5% HCl solution for C1018. The corrosion protection was increased by improving the dose of the synthesized compound and reached 98.5% at 42.02 × 10-5 M and 313 K. On the other hand, it was decreased by increasing the temperature and reached 97.9% at the same concentration and 343 K. The parameters of activation and adsorption were calculated and debated. A polarization study revealed that PMBF functioned as a "mixed-kind inhibitor," i.e., affecting both cathodic and anodic processes through their adsorption onto the electrode surface. The adsorption was described by the Langmuir adsorption isotherm. Different techniques were employed as appropriate tools for analyzing the structure of the layer formed on C1018. Density functional theory (DFT) and Monte Carlo (MC) simulations were used to compare the results of the theoretical calculations with the experiments. Finally, an appropriate inhibition mechanism was suggested and discussed.


Evaluation of dHPLC in mutation screening of the APC gene in a Greek FAP cohort.
Germline mutations in the APC gene predispose to colorectal adenomas leading to cancer in over 80% of patients. A multitude of mutations, dispersed throughout the gene, have been described. We wanted to evaluate the usefulness of denaturing high performance liquid chromatography (dHPLC) for mutation screening. Ten amplicons containing 14 mutations in the APC, previously identified by sequencing in 22 FAP patients, were analysed by dHPLC. dHPLC was also used to screen members of a family for a mutation identified in the proband. We analysed 10 amplicons under a total of 59 temperatures. Successful results were obtained from 51 out of 59 tested temperatures (86.4%). In all cases a different heteroduplex-homoduplex pattern was obtained from mutant DNA in at least two of the temperatures. All 14 mutations identified by sequencing were also detected using dHPLC. Sequence analysis of a large family confirmed the dHPLC results. Using dHPLC we detected all mutations previously identified by sequencing.


Calculation spreadsheet for uncertainty estimation of measurement results in gamma-ray spectrometry and its validation for quality assurance purpose.
An Excel calculation spreadsheet has been developed to estimate the uncertainty of measurement results in γ-ray spectrometry. It considers all relevant uncertainty components and calculates the combined standard uncertainty of the measurement result. The calculation spreadsheet has been validated using two independent open access software and is available for download free of charge at: https://nucleus.iaea.org/rpst/ReferenceProducts/Analytical_Methods/index.htm. It provides a simple and easy-to-use template for estimating the uncertainty of γ-ray spectrometry measurement results and supports the radioanalytical laboratories seeking accreditation for their measurements using γ-ray spectrometry.


Community-acquired pneumonia in children: a look at the IDSA guidelines.
This review of the guidelines can help you adjust your care according to your patient's age and disease severity.


Anomalous Landau quantization in intrinsic magnetic topological insulators.
The intrinsic magnetic topological insulator, Mn(Bi1-xSbx)2Te4, has been identified as a Weyl semimetal with a single pair of Weyl nodes in its spin-aligned strong-field configuration. A direct consequence of the Weyl state is the layer dependent Chern number, [Formula: see text]. Previous reports in MnBi2Te4 thin films have shown higher [Formula: see text] states either by increasing the film thickness or controlling the chemical potential. A clear picture of the higher Chern states is still lacking as data interpretation is further complicated by the emergence of surface-band Landau levels under magnetic fields. Here, we report a tunable layer-dependent [Formula: see text] = 1 state with Sb substitution by performing a detailed analysis of the quantization states in Mn(Bi1-xSbx)2Te4 dual-gated devices-consistent with calculations of the bulk Weyl point separation in the doped thin films. The observed Hall quantization plateaus for our thicker Mn(Bi1-xSbx)2Te4 films under strong magnetic fields can be interpreted by a theory of surface and bulk spin-polarised Landau level spectra in thin film magnetic topological insulators.


A Qualitative Study of Underrepresented Minority (URM) Student Pharmacists' Intersectionality and Professional Identity Formation.
To determine how underrepresented minority (URM) student pharmacists' intersectionality affects professional identity formation early in their academic career. A qualitative study was undertaken. All students from Classes 2022 through 2025 at Texas A&M University School of Pharmacy were required to engage in reflection on a personal statement of philosophy of practice early in their first year of pharmacy as part of the structured longitudinal co-curricular course requirement. Statements of the URM students who referenced their intersecting identities were selected for deductive analysis per Bingham and Witkowsky and inductive analysis using Lincoln and Guba's approach to content analysis. Of the 221 URM student pharmacists within the 4 cohorts who submitted a statement, 38 statements (92% Hispanic students) met the inclusion criteria. Student hometowns and the identity domains of the individual, relational, and collective were selected a priori for the deductive analysis. Students most often referenced individual identity characteristics that fit under the Principles I, IV, V, and VII of the Code of Ethics for Pharmacists. Three themes emerged from the inductive analysis: (1) defining experiences and resulting realizations, (2) motivating forces, and (3) aspirations as a pharmacist. A working hypothesis was developed. The URM students' intersecting identities (race, ethnicity, socioeconomic class, and belonging to an underserved community) influenced their early professional identity formation. The desire to bring about racial uplift was observed among the Hispanic students as early in their P1 year through the School's required co-curricular reflection. Such reflective practice serves as an effective vehicle for the students to recognize their intersecting identities that impact their professional identity.


circMTDH.4/miR-630/AEG-1 axis participates in the regulation of proliferation, migration, invasion, chemoresistance, and radioresistance of NSCLC.
Astrocyte elevated gene-1 (AEG-1) plays a critical role in the development, progression, and metastasis of a variety of cancers, including non-small-cell lung cancer (NSCLC). The objective of the current study is to unravel the upstream signaling of AEG-1. A cohort of 28 NSCLC tissues and 30 normal tissues were collected. Quantitative reverse transcription-polymerase chain reaction and Western blotting were used to examine AEG-1, migration, and invasion related markers in NSCLC cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay coupled with colony formation assay were conducted to monitor cell growth. Transwell assay was performed to determine cell migration and invasion. Apoptotic cells were detected by costaining with Annexin-V-fluorescein isothiocyanate and propidium iodide. Immunofluorescent staining was used to observe the levels of migration and invasion related markers. Xenograft models were used to investigate tumor formation in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation were carried out to determine the interaction between circMTDH.4 and miR-630, as well as the associated between miR-630 and AEG-1. AEG-1 was highly expressed in NSCLC tissues and cell lines. Silencing of AEG-1 inhibited cell proliferation, migration, invasion, and chemoresistance/radioresistance in NCI-H1650 and A549 cells. circMTDH.4 regulated AEG-1 expression via sponging miR-630. Knockdown of circMTDH.4 and/or overexpression of miR-630 inhibited chemoresistance and radioresistance in NSCLC cells, whereas overexpression of AEG-1 or knockdown of miR-630 exerted rescue effects. circMTDH.4/miR-630/AEG-1 axis is responsible for chemoresistance and radioresistance in NSCLC cells.


PP2A and DUSP6 are involved in sphingosylphosphorylcholine-induced hypopigmentation.
Activation of extracellular signal-related kinase (ERK) is involved in decreased melanogenesis by sphingosylphosphorylcholine (SPC). In the present study, we confirmed that SPC activated ERK and that a specific inhibitor of the ERK pathway (PD98059) recovered SPC-induced hypopigmentation. Moreover, we found that SPC significantly reduces protein phosphatase 2A (PP2A) activity in Mel-Ab cells, and that PP2A activator treatment abrogated SPC-induced hypopigmentation. We determined that α-melanocyte-stimulating hormone (α-MSH) increased the expression of dual-specificity phosphatase 6 (DUSP6), an ERK phosphatase, in a time-dependent manner. In contrast, SPC decreased the level of DUSP6 in Mel-Ab cells. Furthermore, inhibiting DUSP6 increased ERK activation and subsequently augmented the SPC-induced hypopigmenting effects. Taken together, our data suggest that SPC-induced phosphatase inhibition is also responsible for the hypopigmentary effects.


Severe hypertension development significantly improves progression-free survival in regorafenib treatment for metastatic colorectal cancer.
Regorafenib is the first multikinase inhibitor used for metastatic colorectal cancer (mCRC) treatment. Reports regarding other multikinase inhibitors have suggested that the development of hypertension is associated with improved clinical benefits. We aimed to reveal the relationship between the development of severe hypertension and regorafenib efficacy in an mCRC real-world setting. Patients with mCRC (n = 100) who received regorafenib were assessed retrospectively. The primary endpoint was a comparison of progression-free survival (PFS) between patients with and without ≥ grade 3 hypertension. The secondary endpoints were overall survival (OS), disease control rate (DCR), and adverse effects. Patients developing ≥ grade 3 hypertension accounted for 30%, and obtained significantly longer PFS than control patients (median PFS of 53 and 56 days, 95% confidence interval [CI] of 46-144 and 49-63 days, respectively; P = 0.04). In contrast, OS and DCR were not statistically different between the groups (P = 0.13 and P = 0.46, respectively). The incidence and severity of adverse effects were not significantly different, except for hypertension. Treatment interruption was significantly more frequent in patients with hypertension (P = 0.04). Multivariate Cox hazard analysis suggested that the development of ≥ grade 3 severe hypertension was an independent factor for improved PFS (adjusted hazard ratio 0.57, 95% CI 0.35-0.93; P = 0.02). In contrast, baseline hypoalbuminemia was associated with a worse PFS (1.85, 1.14-3.01; P = 0.01). We have revealed that patients who develop severe hypertension after regorafenib treatment for mCRC have improved PFS. Management of hypertension is important for effective treatment with less burden; therefore, further evaluation is needed.


Substance K: a novel mammalian tachykinin that differs from substance P in its pharmacological profile.
The primary structure of one of the bovine brain substance P precursors has shown the existence of a second mammalian tachykinin sequence, named substance K, that is remarkably homologous to that of the amphibian peptide kassinin. In this study, three substance K sequences were chemically synthesized and were submitted to parallel bioassays with kassinin, substance P and physalaemin. The results show that the three substance K peptides all possess biological activities characteristic of the tachykinin family and that their biological activities more closely resemble those of kassinin than those of substance P or physalaemin. This suggests that substance K may have a physiological role which is related to but different from that of substance P in mammalian organisms.


Studies on the absorption of homologous and heterologous IgG in artificially reared newborn pigs.
The interaction of homologous and heterologous IgG during intestinal absorption was investigated using five groups of newborn piglets (50 animals in total). The diet, given via a stomach tube, was different in each group during the first 24 h. Group I received bovine colostrum, group II bovine colostrum and porcine IgG solution, group III bovine and porcine colostrum, group IV bovine colostrum and intraperitoneally applied monomeric porcine IgG, and group V received a glucose diet with no immunoglobulins. Feeding was based on bovine colostrum between the 2nd and 6th days after birth, followed by a milk replacer during the rest of the experimental period. The serum concentrations of homologous and heterologous IgG were monitored from birth to 10 weeks of age. The total serum IgG content (homologous + heterologous) of newborns was almost equal in groups I-IV at 24 h. Porcine IgG from endogenous synthesis was detectable in the serum of groups I and V two weeks postpartum. The heterologous IgG absorbed from bovine colostrum produced nearly the same serum concentration in groups II and III: hence the different components of porcine colostrum did not influence the absorption of heterologous IgG. Intraperitoneal application of 1.3 g porcine IgG in group IV resulted in a delay of the synthesis of endogenous IgG. The average half-life of heterologous IgG in the serum of groups I-IV was almost exactly the same, showing that the porcine colostrum or IgG solution did not modify the half-life of bovine IgG.(ABSTRACT TRUNCATED AT 250 WORDS)


Rotary dental instruments and the potential risk of transmission of infection: herpes simplex virus.
A laboratory model of herpes simplex virus infection was used to assess the potential contamination of dental handpieces. When contaminated instruments were treated with surface disinfection and internal chemical disinfection, viable virus was eliminated in all instruments.


Should condom use be promoted for contraception to prevent transmission of sexual transmitted diseases and AIDS? ACSF Group. French National Survey of Sexual behavior.
This study is an exploration of the relationship between the use of oral contraceptive or intrauterine device and condom use. The results should help us better understand how promoting condoms for contraception as compared to sexually transmitted disease prophylaxis might be an effective way of increasing their use in certain populations. Women not involved in stable relationships were selected from the French National Survey on Sexual Behaviour using multi-stage probability sampling. We compared frequency of condom use at the last sexual intercourse by women who were using prescribed contraception with that by women who did not. Odds ratios (OR) were adjusted for age, duration of the relationship, education, type of partner and number of partners in the last 12 months. Overall, no difference was found in the frequency of condom use during the last sexual intercourse by women who were using prescribed contraception compared with women who were not. A more frequent use of condoms tended to be associated with the absence of contraception in relationships of less than three months' duration (adjusted OR: 4.5; 95% CI: 0.7-33.3) and for women of 25 to 34 years of age (adjusted OR: 2.4; 95% CI: 0.8-7.1). Many factors other than contraceptive practice influence the use of condoms. Nevertheless, our results suggest that reproductive issue should be taken into account in specific subgroups of the population when developing policies to prevent sexual transmission of HIV.


Integrating preferences into health status assessment for amyotrophic lateral sclerosis: the ALS Utility Index.
We developed a preference-based measure, the Amyotrophic Lateral Sclerosis Utility Index (ALSUI), allowing computation of US population-based utility weights for the wide range of health states observed among ALS patients. A multi-attribute utility approach was used. An ALS Health State Classification System was developed comprising the following attributes with different severity levels: Speech and Swallowing (A1); Eating, Dressing, and Bathing (A2); Leg Function (A3); and Respiratory Function (A4). An internet-based survey was administered to a random sample of the US population to assess preferences for ALS health states based on this system using visual analog scale (VAS) and standard gamble (SG) questions. Using the VAS and SG data from 1374 individuals in the general population, utility functions were computed that corresponded to each severity level within A1, A2, A3, and A4. ALSUI scores for a given patient are computed by inputting his corresponding utility functions into the following multiplicative formula: ALSUI score = 1.06 x (A1 x A2 x A3 x A4) - 0.06 on a scale where 0.0 reflects death and 1.0 reflects healthy. This study provides a useful tool for classifying ALS patients and determining a general public-based utility score for ALS health states.


Adult-onset Still's disease and pregnancy: about ten cases and review of the literature.
Little is known about the interactions between adult-onset Still's disease (AOSD) and pregnancy. In an attempt to clarify the link between these 2 conditions, we retrospectively analyzed patients registered as suffering from AOSD seen in our university hospital. A total of 57 patients, among them 30 women, were diagnosed. Ten pregnancies in 8 women were identified. Three cases manifested AOSD in their first trimester, all treated with prednisone. Premature births and flares occurred in 2 patients. One patient developed a monocyclic AOSD during her second pregnancy's postpartum. In the 4 other cases, AOSD was known and quiescent before pregnancy. One patient had 2 pregnancies without any flare or complication. One patient experienced her first pregnancy while under treatment and presented a late flare 8 months after delivery. The third patient developed exacerbation in the first trimester of her second pregnancy which was treated with IgIV alone. The last one presented her first pregnancy 7 years after diagnosis. A prednisone-treated systemic flare occurred during the first trimester without later complication. Based on our own experience and the analysis of only two series of the literature, including, respectively, 4 and 5 patients, we suggest that two settings could be distinguished. First, AOSD can occur during pregnancy and can be responsible for obstetrical complications. Then, in patients with known AOSD, the second trimester and postpartum appear to be periods exposing to disease recurrence. Thus, we recommend a close multidisciplinary monitoring by a rheumatologist and an obstetrician prior to, during and after pregnancies.


Profiling of hormones and related metabolites in seed dormancy and germination studies.
Seed dormancy and germination are regulated by several plant hormones, such as abscisic acid, gibberellin, auxin (indole-3-acetic acid), ethylene, and brassinosteroid. Endogenous concentrations of a hormone are determined by the balance between biosynthesis and deactivation, and contribute to the regulation of physiological responses. Therefore, profiling of all hormones and their metabolites (hormonome) is a powerful approach to elucidate the regulatory networks of hormone metabolism. The methods involved in the use of liquid chromatography-electrospray ionization-tandem mass spectrometry to develop a high-sensitive and high-throughput hormonome platform are described in this chapter.


Sustainable antibullying program implementation: School profiles and predictors.
We examined the sustainability of the KiVa antibullying program in Finland from its nationwide roll-out in 2009 to 2016. Using latent class analyses, we identified four different patterns of implementation. The persistent schools (43%) maintained a high likelihood of participation throughout the study period. The awakened (14%) had a decreasing trend during the first years, but then increased the likelihood of program participation. The tail-offs (20%) decreased in the likelihood of participating after the third year, and the drop-offs (23%) already after the first year. The findings suggest that many schools need support during the initial years to launch and maintain the implementation of evidence-based programs; yet a large proportion of schools manage to sustain the program implementation for several years. The logistic regression analyses showed that large schools persisted more likely than small schools. Lower initial level of victimization was also related to the sustainability of the program. Finally, persistent program participation was predicted by several school-level actions during the initial years of implementing the program. These results imply that the sustainability of evidence-based programs could be enhanced by supporting and guiding schools when setting up the program during the initial implementation.


Depression in schizophrenia: current guidelines to treatment.
Depressive symptoms and syndromes in schizophrenia are common but heterogeneous with respect to etiology, presentation, course, and treatment. Based on a comprehensive differential diagnosis that identifies ten clinical subgroups, the authors review relevant treatment studies and offer current treatment guidelines. The clinical recommendations focus on addressing underlying problems such as medication side effects and substance abuse, attempting to identify and treat medication-responsive syndromes, and preventing suicide. The categories and treatments presented here are expected to evolve as researchers continue to elucidate clinically meaningful syndromes and to develop specific treatments. Nevertheless, current knowledge suggests that many schizophrenics with depression and depression-like symptoms can be treated effectively.


Coaction versus reciprocity in continuous-time models of cooperation.
Cooperating animals frequently show closely coordinated behaviours organized by a continuous flow of information between interacting partners. Such real-time coaction is not captured by the iterated prisoner's dilemma and other discrete-time reciprocal cooperation games, which inherently feature a delay in information exchange. Here, we study the evolution of cooperation when individuals can dynamically respond to each other's actions. We develop continuous-time analogues of iterated-game models and describe their dynamics in terms of two variables, the propensity of individuals to initiate cooperation (altruism) and their tendency to mirror their partner's actions (coordination). These components of cooperation stabilize at an evolutionary equilibrium or show oscillations, depending on the chosen payoff parameters. Unlike reciprocal altruism, cooperation by coaction does not require that those willing to initiate cooperation pay in advance for uncertain future benefits. Correspondingly, we show that introducing a delay to information transfer between players is equivalent to increasing the cost of cooperation. Cooperative coaction can therefore evolve much more easily than reciprocal cooperation. When delays entirely prevent coordination, we recover results from the discrete-time alternating prisoner's dilemma, indicating that coaction and reciprocity are connected by a continuum of opportunities for real-time information exchange.


Immune history profoundly affects broadly protective B cell responses to influenza.
Generating a broadly protective influenza vaccine is critical to global health. Understanding how immune memory influences influenza immunity is central to this goal. We undertook an in-depth study of the B cell response to the pandemic 2009 H1N1 vaccine over consecutive years. Analysis of monoclonal antibodies generated from vaccine-induced plasmablasts demonstrated that individuals with low preexisting serological titers to the vaccinating strain generated a broadly reactive, hemagglutinin (HA) stalk-biased response. Higher preexisting serum antibody levels correlated with a strain-specific HA head-dominated response. We demonstrate that this HA head immunodominance encompasses poor accessibility of the HA stalk epitopes. Further, we show polyreactivity of HA stalk-reactive antibodies that could cause counterselection of these cells. Thus, preexisting memory B cells against HA head epitopes predominate, inhibiting a broadly protective response against the HA stalk upon revaccination with similar strains. Consideration of influenza exposure history is critical for new vaccine strategies designed to elicit broadly neutralizing antibodies.


The effects of isoflurane on adrenomedullin-induced haemodynamic responses in pithed rats.
Adrenomedullin is a potent vasodilatory peptide. The mechanisms of adrenomedullin-induced responses are via guanine nucleotide guanosine 5'-triphosphate-binding protein (G-protein)-coupled receptor activation and are similar to those of calcitonin gene-related peptide (CGRP). Previously, we reported that sevoflurane and isoflurane inhibit CGRP-induced haemodynamic responses. The effects of volatile anaesthetics on adrenomedullin-induced haemodynamic responses, however, are unclear. We hypothesized that the volatile anaesthetic isoflurane inhibits adrenomedullin-induced haemodynamic responses. We studied the effects of isoflurane on adrenomedullin-induced haemodynamic responses in pithed rats, which enables us to evaluate the direct cardiovascular effects of drugs without interference from centrally mediated circulatory reflexes. Male Wistar rats were pithed by inserting a stainless-steel rod into the spinal cord. Following median sternotomy, a flow probe was placed around the ascending aorta to measure aortic blood flow. Mean arterial pressure and cardiac output were maintained at approximately 100 mmHg and 50 mL min-1, respectively, with continuous infusion of norepinephrine. After 30 min inhalation of isoflurane (1%, or 2%) in oxygen, or only oxygen, adrenomedullin (1, 3, 10 or 30 microg kg-1) was administered intravenously. Adrenomedullin administration induced a transient increase followed by a persistent decrease in mean arterial pressure and cardiac output. Isoflurane (2%) significantly inhibited the initial increase in mean arterial pressure and the later decrease in mean arterial pressure and systemic vascular resistance. Isoflurane inhibits adrenomedullin-induced vasodilation and positive inotropic effect in pithed rats. Isoflurane might inhibit the adrenomedullin receptor-mediated response, which is a common pathway for both actions.


[Blood heat exchangers for the artificial heart using a radioisotope power source].
A design of a vascular heat exchanger enabling it to establish in experiments with animals the degree of the possible specific-capacity thermal loads has been devised. The performance results may be taken account of in designing implantable appliances of assistive circulation and artificial heart.


Seasonal influences on admissions in schizophrenia and affective disorder in Ireland.
Although the seasonal patterns of admissions of affective disorder have been extensively studied, less attention has been given to the seasonal admission patterns of schizophrenia. The traditional method of aggregating the data over a study period, rather than analysing by year of admission may obscure potentially relevant fluctuations in the seasonal pattern. We examined the year-to-year variation in the admission patterns of schizophrenia and affective disorder in Ireland. Using the National Psychiatric Inpatient Reporting System (NPIRS), individuals admitted with an ICD-9/10 diagnosis of a first episode of schizophrenia or affective disorder during the 6-year period 1989-1994 were identified. Seasonal variations in their admission patterns were examined statistically and graphically. There was a significant seasonal variation in the monthly admission patterns of both schizophrenia and affective disorder. This pattern was more marked for individuals with affective disorder. However, the seasonal pattern was not constant from year to year, particularly for schizophrenia.


An electrochemical approach to the guanacastepenes.
An asymmetric approach toward the [6-7-5] ring system of the guanacastepenes is described. [structure: see text]


Pathways connecting inflammation and cancer.
Chronic and persistent inflammation contributes to cancer development and can predispose to carcinogenesis. Infection-driven inflammations are involved in the pathogenesis of approximately 15-20% of human tumors. However, even tumors that are not epidemiologically linked to pathogens are characterized by the presence of an inflammatory component in their microenvironment. Hallmarks of cancer-associated inflammation include the presence of infiltrating leukocytes, cytokines, chemokines, growth factors, lipid messengers, and matrix-degrading enzymes. Schematically, two interrelated pathways link inflammation and cancer: (1) genetic events leading to neoplastic transformation promote the construction of an inflammatory milieu; (2) tumor-infiltrating leukocytes, in particular macrophages, are prime regulators of cancer inflammation. Thus, an intrinsic pathway of inflammation (driven in tumor cells), as well as an extrinsic pathway (in tumor-infiltrating leukocytes) have been described and both contribute to tumor progression.


Corrigendum to "Correlation of Clinicopathological Profile, Prognostic Factors, and Survival Outcomes with Baseline Alfa-Fetoprotein Levels in Patients with Hepatocellular Carcinoma: A Biomarker that is Bruised but Not Broken" [J Clin Exp Hepatol 12 (2022) 841-852].
[This corrects the article DOI: 10.1016/j.jceh.2021.11.006.].


A new validated HPLC-FLD method for detecting ochratoxin A in dry-cured meat and in blue cheese.
In the present study, a fast and sensitive method for the quantification of ochratoxin A in two lipidicproteic food matrices has been developed. In particular, the sample preparation procedure has been optimized for dry-cured meat products and blue cheeses and tested for several validation parameters (LOD, LOQ, recovery, repeatability and within-laboratory precision). The procedure has been then applied to several dry-cured meat products and blue cheeses from the market.Ochratoxin A has been occasionally found in dry-cured and smoked ham from the market and the contamination occurred both in the outer and in the inner part of the products. Concerning the blue cheese, the occurrence of ochratoxin A is reported for the first time: OTA was occasionally found at low levels (0.1-3 μg/kg) in commercial samples of Roquefort from France and Gorgonzola from Italy, opening a new issue for risk assessment and quality control.


A case of intra-operative ventricular fibrillation: Electro-cauterization, undiagnosed Takotsubo cardiomyopathy or long QT syndrome?
Cardiac arrest in the perioperative setting is an extremely serious event that is estimated to occur between 4.6 and 19.7 per 10,000 anesthetics.(1-5) While risk factors for cardiac complications can be identified pre- operatively, in many cases workup of risk factors are not indicated by standard pre-operative testing guidelines. We present a case of a 47-year-old female undergoing an elective bilateral mastectomy who suddenly converted to ventricular fibrillation. While ventricular fibrillation is not a unique finding, our search for its etiology revealed two previously undiagnosed cardiac conditions, and possible electro- cautery induced ventricular fibrillation. In this case study, we discuss the possible etiology of ventricular fibrillation in our patient and highlight the importance pre-operative patient investigation and history provide. Searching for the potential causes that may have contributed to the cardiac arrest is an extremely useful exercise as it allows us to better prepare patients pre-operatively, improve intra-operative care, and prevent future cardiac events.


Tool design for prevention of hand and wrist injuries.
Incorrect hand tool designs can cause a variety of cumulative trauma disorders. Design elements of size, shape, texture, purpose, ease of operation, shock absorption, and weight must be properly applied in the design process to fulfill the physical safety needs of consumers and working people and to prevent the appearance of pathologic changes in the tissues of the hand and wrist.


[Current status and future potentials of multislice computed tomography].
This overview article gives a short introduction into present status and future potential of multislice computed tomography. The main benefits of established 4- to 16-slice CT systems are larger volume coverage, better utilization of the X-ray tube output and above all improved transverse resolution. Spiral examinations with 16 submillimeter slices are a breakthrough on the way towards isotropic scanning for routine applications. ECG-controlled CT-examinations of the heart benefit from both the improved temporal and spatial resolution of the new generation of 16-slice CT systems. Compared to 4-slice scanners, cardiac examinations are clinically more robust. The most important potential for improvement of multislice cardiac CT is a further enhancement of temporal resolution which requires increased gantry rotation speed for robust clinical performance. Combined systems such as CT PET scanners will gain increasing importance in the near future. In general radiology the race for more slices will continue, finally leading to the introduction of CT systems with area-detectors.


Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces: Mechanics of mitotic spindle positioning.
Tissues are shaped and patterned by mechanical and chemical processes. A key mechanical process is the positioning of the mitotic spindle, which determines the size and location of the daughter cells within the tissue. Recent force and position-fluctuation measurements indicate that pushing forces, mediated by the polymerization of astral microtubules against- the cell cortex, maintain the mitotic spindle at the cell center in Caenorhabditis elegans embryos. The magnitude of the centering forces suggests that the physical limit on the accuracy and precision of this centering mechanism is determined by the number of pushing microtubules rather than by thermally driven fluctuations. In cells that divide asymmetrically, anti-centering, pulling forces generated by cortically located dyneins, in conjunction with microtubule depolymerization, oppose the pushing forces to drive spindle displacements away from the center. Thus, a balance of centering pushing forces and anti-centering pulling forces localize the mitotic spindles within dividing C. elegans cells.


Biocompatible reduced graphene oxide stimulated BMSCs induce acceleration of bone remodeling and orthodontic tooth movement through promotion on osteoclastogenesis and angiogenesis.
We has synthesized the biocompatible gelatin reduced graphene oxide (GOG) in previous research, and in this study we would further evaluate its effects on bone remodeling in the aspects of osteoclastogenesis and angiogenesis so as to verify its impact on accelerating orthodontic tooth movement. The mouse orthodontic tooth movement (OTM) model tests in vivo showed that the tooth movement was accelerated in the GOG local injection group with more osteoclastic bone resorption and neovascularization compared with the PBS injection group. The analysis on the degradation of GOG in bone marrow stromal stem cells (BMSCs) illustrated its good biocompatibility in vitro and the accumulation of GOG in spleen after local injection of GOG around the teeth in OTM model in vivo also didn't influence the survival and life of animals. The co-culture of BMSCs with hematopoietic stem cells (HSCs) or human umbilical vein endothelial cells (HUVECs) in transwell chamber systems were constructed to test the effects of GOG stimulated BMSCs on osteoclastogenesis and angiogenesis in vitro. With the GOG stimulated BMSCs co-culture in upper chamber of transwell, the HSCs in lower chamber manifested the enhanced osteoclastogenesis. Meanwhile, the co-culture of GOG stimulated BMSCs with HUVECs showed a promotive effect on the angiogenic ability of HUVECs. The mechanism analysis on the biofunctions of the GOG stimulated BMSCs illustrated the important regulatory effects of PERK pathway on osteoclastogenesis and angiogenesis. All the results showed the biosecurity of GOG and the biological functions of GOG stimulated BMSCs in accelerating bone remodeling and tooth movement.


Prey size selection and distance estimation in foraging adult dragonflies.
To determine whether perching dragonflies visually assess the distance to potential prey items, we presented artificial prey, glass beads suspended from fine wires, to perching dragonflies in the field. We videotaped the responses of freely foraging dragonflies (Libellula luctuosa and Sympetrum vicinum-Odonata, suborder Anisoptera) to beads ranging from 0.5 mm to 8 mm in diameter, recording whether or not the dragonflies took off after the beads, and if so, at what distance. Our results indicated that dragonflies were highly selective for bead size. Furthermore, the smaller Sympetrum preferred beads of smaller size and the larger Libellula preferred larger beads. Each species rejected beads as large or larger than their heads, even when the beads subtended the same visual angles as the smaller, attractive beads. Since bead size cannot be determined without reference to distance, we conclude that dragonflies are able to estimate the distance to potential prey items. The range over which they estimate distance is about 1 m for the larger Libellula and 70 cm for the smaller Sympetrum. The mechanism of distance estimation is unknown, but it probably includes both stereopsis and the motion parallax produced by head movements.


Fetal fibronectin detection in preterm labor: evaluation of a prototype bedside dipstick technique and cervical assessment.
The aims of this study were to evaluate a prototype bedside test for fetal fibronectin detection in women with symptoms of preterm labor, to compare the efficacy of obtaining fetal fibronectin swabs with and without a speculum, and to assess the value of combining the fetal fibronectin test with cervical dilatation for predicting delivery within 10 days. This investigation prospectively studied a cohort of women with symptoms of preterm labor (n = 121), gestational age between 24 and 33 6/7 weeks, and cervical dilatation </=3 cm. Vaginal swabs for fibronectin testing with the bedside dipstick Fetal Fibronectin Membrane Immunoassay test (Adeza Biomedical, Sunnyvale, Calif) were obtained with and without a speculum. Results were not available to the clinicians. Twenty-two percent of the fetal fibronectin samples collected with a speculum (27/121) yielded positive results. The incidence of delivery within 10 days of testing was 14% (17/121). Fetal fibronectin detection predicted delivery within 10 days with sensitivity, specificity, and positive and negative predictive values of 65%, 85%, 41%, and 94%, respectively. The positive and negative likelihood ratios were 4.3 and 0.41, respectively. There was substantial association between samples obtained with and without a speculum (Cohen kappa statistic 0.65, 95% confidence interval 0.44-0.87). Cervical dilatation >/=1 cm predicted delivery within 10 days with sensitivity, specificity, and positive and negative predictive values of 71%, 87%, 46%, and 95%, respectively, with positive and negative likelihood ratios of 5.5 and 0.33, respectively. Combination of fetal fibronectin testing with cervical dilatation >/=1 cm did not significantly improve the fetal fibronectin test characteristics. After exclusion of women with slight vaginal bleeding, cervical dilatation >/=1 cm and fetal fibronectin status remained the only independent variables associated with delivery within 10 days. Fetal fibronectin testing according to this prototype may have a limited role in clinical decision analysis. In this study a cervical dilatation >/=1 cm had predictive values equivalent to those of the fetal fibronectin test, and it should be evaluated further in a clinical setting.


Network Pharmacology and Molecular Docking Analysis Exploring the Mechanism of Tripterygium wilfordii in the Treatment of Oral Lichen Planus.
Background: Oral lichen planus (OLP) is an infrequent autoimmune disease of the oral mucosa, which affects up to 2% of the world population. An investigation of Tripterygium wilfordii's mechanism of action for treating OLP was conducted, and a theoretical basis was provided for improving current treatment regimens. Materials and Methods: We used a network pharmacological approach to gain insight into the molecular mechanism of Tripterygium wilfordii in the treatment of OLP. Then, potential protein targets between Tripterygium wilfordii and OLP were analyzed through a drug-target network. This was followed by KEGG enrichment analysis and Gene Ontology (GO) classification. Finally, for molecular docking, AutoDock Vina was used. Results: A protein-protein interaction (PPI) network was constructed by analyzing the common targets of a total of 51 wilfordii-OLP interactions from different databases. The GO and KEGG enrichment analyses showed that the treatment of OLP with Tripterygium wilfordii mainly involves lipopolysaccharide response, bacterial molecular response, positive regulation of cytokine production, and leukocyte proliferation, and the signaling pathways mainly include the AGE-RAGE, NF-κB, Toll-like receptor, IL-17, HIF-1, and TNF signaling pathways. The molecular docking results showed that β-sitosterol, kaempferol, hederagenin, and triptolide have a higher affinity for AKT1, TNF, CASP3, and PTGS2, respectively. Based on the CytoNCA analysis of common targets, 19 key targets, including AKT1, TNF, VEGFA, STAT3, CXCL8, PTGS2, TP53, and CASP3, and their connections were identified. Conclusions: Preliminarily, this study reveals that Tripterygium wilfordii interferes with OLP by interacting with multiple targets through multiple accesses, as validated by molecular docking.


The nature of anhedonia and avolition in patients with first-episode schizophrenia.
Patients with schizophrenia have intact ability to experience emotion, but empirical evidence suggests that they fail to translate emotional salience into effortful behaviour. Previous research in patients with chronic schizophrenia suggests that working memory is important in integrating emotion and behaviour. This study aimed to examine avolition and anhedonia in patients with first-episode schizophrenia and clarify the role of working memory in emotion-behaviour coupling. We recruited 72 participants with first-episode schizophrenia and 61 healthy controls, and used a validated emotion-inducing behavioural paradigm to measure participants' affective experiences and how experienced emotion coupled with behaviour. Participants were given the opportunity to expend effort to increase or decrease their exposure to emotion-inducing photographs. Participants with schizophrenia having poor working memory were compared with those with intact working memory in their liking and emotion-behaviour coupling. Patients with first-episode schizophrenia experienced intact 'in-the-moment' emotion, but their emotion was less predictive of the effort expended, compared with controls. The emotion-behaviour coupling was significantly weaker in patients with schizophrenia with poor working memory than in those with intact working memory. However, compared with controls, patients with intact working also showed substantial emotion-behaviour decoupling. Our findings provide strong evidence for emotion-behaviour decoupling in first-episode schizophrenia. Although working memory deficits contribute to defective translation of liking into effortful behaviour, schizophrenia alone affects emotion-behaviour coupling.


Social isolation produces anxiety-like behaviors and changes PSD-95 levels in the forebrain.
Isolation rearing induces profound behavioral and neurochemical abnormalities in rodents. However there have been many controversies with its anxiogenic-like effects using models like elevated-plus maze. In the current study we aimed to address this by using one novelty-based anxiety paradigm that has been largely overlooked in previous isolation rearing studies. We found that eight-week isolation rearing produced potent anxiogenic-like effects in novelty-induced hypophagia test in mice. We also demonstrated PSD-95 levels were elevated in the hippocampus and amygdala and reduced in the frontal cortex after social isolation. This study provides further behavioral and neurochemical evidence to support that isolation rearing can produce anxiogenic-like effects in rodents.


Evolution of the N-Terminal Regulation of Cardiac Troponin I for Heart Function of Tetrapods: Lungfish Presents an Example of the Emergence of Novel Submolecular Structure to Lead the Capacity of Adaptation.
Troponin-based Ca2+ regulation of striated muscle contraction emerged approximately 700 million years ago with largely conserved functions during evolution. Troponin I (TnI) is the inhibitory subunit of troponin and has evolved into three muscle type-specific isoforms in vertebrates. Cardiac TnI is specifically expressed in the adult heart and has a unique N-terminal extension implicating a specific value during natural selection. The N-terminal extension of cardiac TnI in higher vertebrates contains β-adrenergic-regulated protein kinase A (PKA) phosphorylation sites as a mechanism to enhance cardiac muscle relaxation and facilitate ventricular filling. Phylogenic studies showed that the N-terminal extension of cardiac TnI first emerged in the genomes of early tetrapods as well as primordial lobe-finned fishes such as the coelacanth whereas it is absent in ray-finned fish. This apparently rapid evolution of β-adrenergic regulation of cardiac function suggests a high selection value for the heart of vertebrate animals on land to work under higher metabolic demands. Sequencing and PKA phosphorylation data showed that lungfish cardiac TnI has evolved with an amphibian-like N-terminal extension with prototype PKA phosphorylation sites while its overall structure remained fish like. The data demonstrate that the submolecular structure of TnI may evolve ahead of the whole protein for cardiac muscle contractility to adapt to new environmental conditions. Understanding the evolution of the β-adrenergic regulation of TnI and cardiac adaptation to the increased energetic demands of life on land adds knowledge for the treatment of human heart diseases and failure.


[Ethics, communication and interdisciplinary collaboration-by law?!]
The coronavirus pandemic of recent months has highlighted the fact that death is still a taboo regardless of the progress that has been made in palliative care. The concept of advance care planning is still not adequately practiced by individuals yet and we do not know enough about what is important for people in the last phase of their lives. Nurses can play an important in discussions about values and the ideas of what is important when death is getting closer. In Germany, there is a law (§ 132g Abs. 3 Sozialgesetzbuch V) that makes it possible to receive remuneration for these conversations. Hopefully, this is just the first of many steps to further develop ethics, communication and interdisciplinary collaboration.


Thymic epithelial cells derived from the cultures of thymic nurse cells.
Thymic epithelial cells are derived from the cultures of thymic nurse cells. These cultures are free from fibroblasts and macrophages. The epithelial nature of these cells is confirmed by demonstrating the presence of keratin filaments in them. These epithelial cells show heterogeneity in shape, size and distribution of keratin filaments. They contain nonspecific esterase(s) molecules and express both I-A and H-2K antigens.


Association of genetic polymorphisms of glutamate decarboxylase 2 and the dopamine D2 receptor with obesity in Taiwanese subjects.
It has been proposed that glutamate decarboxylase 2 and the dopamine D2 receptor are involved in the brain reward cascade to increase carbohydrate craving and cause eating disorders. We investigated the association between the polymorphisms of the GAD2 and DRD2 genes and obesity with a higher body mass index (BMI) in Taiwanese patients. A retrospective, case-control study at Antai Tian-Sheng Memorial Hospital from 1 January to 31 December 2009. Of 300 subjects enrolled in the study, 132 were obese (BMI≥30 kg/m2) and 168 controls were not obese (BMI≤24 kg/m2). The polymorphisms of GAD2 (+61450 C/A), (+83987 T/A) and DRD2 (S311C) were characterized, respectively, by polymerase chain reaction-restriction fragment length polymorphism. The genotype and allele frequencies of the polymorphisms in this study were statistically analyzed. The genotype and allele frequencies of the GAD2 (+83987 T/A) and DRD2 (S311C) were significantly different between cases and controls (P=.001 for both). The frequencies of TT genotype and T allele of the GAD2 (+83987 T/A) as well as the frequencies of Ser/Cys genotype and Cys allele of DRD2 (S311C) were higher in cases compared to controls (P=.034 and =.036 for both). The study demonstrated a statistically significant difference in the frequency of the GAD2 (+83987 T/A) and DRD2 (S311C) genes between cases and controls in Taiwanese subjects.


Use of a quantitative index of beam modulation to characterize dose conformality: illustration by a comparison of full beamlet IMRT, few-segment IMRT (fsIMRT) and conformal unmodulated radiotherapy.
A technique is presented for characterizing the degree of modulation in an intensity-modulated beam. It is shown that the modulation increases as dose conformality increases. Full intensity-modulated radiation therapy (IMRT) is compared with a two-weight-per-field technique and with simple geometrically conformal beams. It is suggested that each individual planning problem requires some comparative planning of this type because there is no simple answer to the question of the degree to which IMRT improves dose conformality. This depends on the problem geometry, the dose prescription, the cost function, the number of beams and other planning conditions. A methodology is presented for such comparative planning studies and this is illustrated with the solution of two planning problems.


Energy dependence of different steps in the autophagic-lysosomal pathway.
The energy dependence of the autophagic-lysosomal pathway was investigated in isolated rat hepatocytes, using electroinjected [14C]lactose as an autophagy probe and atractyloside to alter intracellular ATP levels. Since autophagocytosed lactose is hydrolyzed in lysosomes, several steps in the pathway could be analyzed. The following observations were made. 1) The overall autophagic degradation of electroinjected [14C]lactose was strongly energy-dependent. More than 85% inhibition was obtained when the ATP content decreased from the control value of 10 mumol/g dry weight to 4 mumol/g dry weight. 2) The initial step, i.e. the autophagic sequestration of [14C]lactose, measured in the presence of vinblastine to prevent transfer of lactose to lysosomes, was as sensitive to small changes in ATP as was the overall lactose degradation. 3) The steady state level of sequestered [14C]lactose remained constant as ATP decreased from 10 to 4 mumol/g dry weight, indicating that the sequestration step and some postsequestrational process were inhibited to a similar extent by ATP depletion. 4) The final step in the pathway, intralysosomal hydrolysis, was measured by allowing [14C]lactose to preaccumulate intralysosomally in the presence of the reversible lysosome inhibitor propylamine. Following propylamine removal and inhibition of further sequestration by 3-methyladenine, ATP-dependent hydrolysis of the intralysosomal [14C]lactose could be demonstrated. However, this hydrolysis step was not as sensitive to small changes in ATP as was the sequestration step or the overall autophagic lactose degradation. Control of the autophagic-lysosomal pathway in response to energy deprivation would therefore not seem to occur at the lysosomal level, but may be exerted both at the sequestration step and at a postsequestrational, prelysosomal step.


A rare case of paraganglioma of the sella with bone metastases.
Sellar paragangliomas are very rare lesions with only 11 previous cases described in the literature. We present a further case of sellar paraganglioma. The patient is a 17-year-old man who developed headache, visual blurring, and diplopia. MRI showed a sellar lesion. Trans-nasal trans-sphenoid biopsy showed features of paraganglioma. He was treated by Stereotactic radiotherapy. Four months after treatment he developed bone metastases which was palliated by radiation, zoledronic acid, and chemotherapy. This is the first case of sellar paraganglioma showing metastases to bone.


Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons.
TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) sodium channel currents were analyzed in acutely dissociated dorsal root ganglion (DRG) neurons isolated from 3-12-d-old and adult rats. Currents were recorded using the whole-cell patch-clamp technique. TTX-R current was more likely to be present in younger animals (3-7 d), whereas TTX-S current was more common in older animals (7-10 d), although TTX-R current was recorded from adult rat DRG neurons. The TTX-R and TTX-S currents differed in their steady-state inactivation, with 50% inactivation voltage at -40 +/- 5 mV (n = 10) for TTX-R currents and -70 +/- 4 mV (n = 10) for TTX-S currents. These current types also differed in their activation kinetics, with 50% activation values of -15 +/- 5 mV (n = 5) for TTX-R currents and -26 +/- 6 mV (n = 5) for TTX-S currents. The interactions of TTX-R and TTX-S channels with various pharmacological agents and divalent cations were studied. The Kd values for TTX-S and TTX-R currents were estimated to be 0.3 nM and 100 microM for TTX, 0.5 nM and 10 microM for saxitoxin, and 50 microM and 200 microM for lidocaine, respectively. TTX-S channels did not exhibit a marked use-dependent block by lidocaine, whereas lidocaine significantly decreased TTX-R current in a use-dependent manner at frequencies ranging from 1 to 33.3 Hz. Several external divalent cations exerted different effects on these current types.(ABSTRACT TRUNCATED AT 250 WORDS)


DEVELOPMENT OF FOCAL CHOROIDAL EXCAVATION IN A CASE OF IDIOPATHIC CHOROIDAL NEOVASCULAR MEMBRANE.
The purpose of this study was to demonstrate the evolution of focal choroidal excavation in a 17-year-old girl on treatment for a choroidal neovascular membrane over a 6-year follow-up. Review of medical and imaging records of a 17-year-old girl who presented with a choroidal neovascular membrane in her left eye treated with multiple intravitreal antivascular endothelial growth factor injections over a period of 6 years. The patient developed recurrent episodes of subretinal hemorrhage that were treated with antivascular endothelial growth factor injections. Over the follow-up period, swept source optical coherence tomography through the lesion revealed progressive reduction in size of the choroidal neovascular membrane complex with the development of acquired focal choroidal excavation.


Cessation of ambulation results in a dramatic loss of trabecular bone density in boys with Duchenne muscular dystrophy (DMD).
Glucocorticoids are currently used to improve muscle strength and prolong ambulation in boys with DMD although the effect on bone health is still unclear. The aim of this study was to compare bone strength in healthy children and boys with DMD and investigate the interaction between diminished muscle function, loss of ambulation and high dose oral steroids, over a two year time frame. Fifty children were studied, 14 healthy boys (HB), 13 boys with DMD who remained ambulant (DMD-RA) and 23 boys with DMD who lost ambulation (DMD-LA). All boys with DMD had taken oral glucocorticoids. Peripheral quantitative computed tomography was used to measure bone geometry, density, strength and muscle mass of the non-dominant tibia and radius. Measurements were made at baseline, 12 and 24 months at the distal metaphysis and mid diaphysis sites. Differences between the three groups were evaluated using ANOVA and a repeated measures model. There were no significant differences in age between the groups: mean age was 9.4, 8.7 and 8.8 years for HB, DMD-RA and DMD-LA, respectively. There was no significant difference in steroid exposure between the DMD groups. However, boys who lost ambulation had significantly lower muscle function at baseline (North Star Ambulatory Assessment DMD-RA 23.6 vs. DMD-LA 18.8; p < 0.05). At baseline, healthy boys had significantly greater trabecular bone density at the distal radius /ulna (23%/27%) and distal tibia/fibula (30%/46%) than boys with DMD (p < 0.05). They also had significantly larger diaphyseal tibiae/fibulae (74%/36%) and radii/ulnae (49%/31%) with thicker corticies and consequently greater bone strength. In contrast, boys with DMD had greater cortical density (4%). Over time, there were small significant differences in the rate of change of both muscle and bone parameters between healthy boys and boys with DMD. For both ambulant and non-ambulant boys with DMD the greatest changes in cortical bone were evident at the tibia. After two years boys with DMD had on average, 63% less bone strength than healthy boys. However, the most strikingly significant difference was in trabecular bone density for boys who became non-ambulant. By 2 years non-ambulant DMD boys had 53% less trabecular bone density at distal tibia than their healthy age matched peers compared with boys who remained ambulant who had 27% less trabecular bone density. In conclusion, bone and muscle strength is reduced for all boys with DMD even while they remain ambulant. However, tibia trabecular bone density loss is significantly accelerated in DMD boys who lose independent ambulation compared to DMD boys who remain ambulant despite equivalent levels of corticosteroid exposure.


Erratum: Summarizing and Communicating on Survival Data According to the Audience: A Tutorial on Different Measures Illustrated with Population-Based Cancer Registry Data [Corrigendum].
[This corrects the article DOI: 10.2147/CLEP.S173523.].


Role of trophic factors GDNF, IGF-1 and VEGF in major depressive disorder: A comprehensive review of human studies.
The neurotrophin hypothesis of major depressive disorder (MDD) postulates that this illness results from aberrant neurogenesis in brain regions that regulates emotion and memory. Notwithstanding this theory has primarily implicated BDNF in the neurobiology of MDD. Recent evidence suggests that other trophic factors namely GDNF, VEGF and IGF-1 may also be involved. The present review aimed to critically summarize evidence regarding changes in GDNF, IGF-1 and VEGF in individuals with MDD compared to healthy controls. In addition, we also evaluated the role of these mediators as potential treatment response biomarkers for MDD. A comprehensive review of original studies studies measuring peripheral, central or mRNA levels of GDNF, IGF-1 or VEGF in patients with MDD was conducted. The PubMed/MEDLINE database was searched for peer-reviewed studies published in English through June 2nd, 2015. Most studies reported a reduction in peripheral GDNF and its mRNA levels in MDD patients versus controls. In contrast, IGF-1 levels in MDD patients compared to controls were discrepant across studies. Finally, most studies reported high peripheral VEGF levels and mRNA expression in MDD patients compared to healthy controls. GDNF, IGF-1 and VEGF levels and their mRNA expression appear to be differentially altered in MDD patients compared to healthy individuals, indicating that these molecules might play an important role in the pathophysiology of depression and antidepressant action of therapeutic interventions.


An Efficient Transformation System for Fast Production of VcCHS Transgenic Blueberry Callus and Its Expressional Analysis.
The Agrobacterium tumefaciens-mediated transformation for blueberries remains less efficient than is desirable. A new leaf callus regeneration and genetic transformation system was investigated in blueberries in this study. The leaf explants of cv. 'Legacy' and 'Northland' were used to establish the stable callus induction system when placed on the woody plant medium (WPM) supplemented with 1.0 mg·L-1 2, 4-D, 0.4 mg·L-1 6-BA for 30 d; then, the callus was sub-cultured in the proliferation medium supplemented with 1.5 mg·L-1 2, 4-D, 0.4 mg·L-1 6-BA in the darkness at 25 °C every 30 days. The co-cultivation of callus with A. tumefaciens was operated on WPM plus 100 μM acetosyringone for 4 days; then, the transferred callus was grown in WPM supplemented with 1.5 mg·L-1 2,4-D, 0.4 mg·L-1 6-BA, 50 mg·L-1 hygromycin, and 200 mg·L-1 cefotaxime. The VcCHS transgenic blueberry callus with both GFP signal and Hyg resistance was obtained from the transformed callus of cv. 'Northland'. The rate of GFP signal detected in the transformed callus was as high as 49.02%, which was consistent with the PCR assay. Collectively, this study provides a highly efficient genetic transformation system in blueberry callus and a powerful approach for the molecular breeding of blueberries.


Perspectives on complement in xenotransplantation.
The crucial role of complement and naturally occurring anti-Gal antibodies in hyperacute rejection of pig transplants to Old World monkeys, apes and humans is well established. This rejection can be prevented by manipulating either system. Although cells, tissues or organs from pigs made transgenic for human complement regulatory proteins escape hyperacute rejection, there is an increasing evidence of a role for complement also in the subsequent acute vascular or delayed xenograft rejection. Furthermore, complement contributes in a general manner to ischemia-reperfusion injury (IRI), irrespective of the organ source. Early complement-mediated endothelial cell activation, although not sufficient to induce hyperacute rejection, may contribute to reduced long-time graft performance. Control of fluid-phase complement activation by soluble complement inhibitors might be an important adjuvant to transgenic organs from the time of organ harvesting through the first post-transplant period. Pharmacologic manipulation of complement is a field in expansion, though still in its infancy. Although an optimal transgenic and cloned pig may be close to reality, the role of complement in xenotransplantation needs to be fully elucidated and a treatment regimen for fluid-phase inhibition is warranted. The story of complement in xenotransplantation is not completed but under continuous revision.


Cloning and expression of in silico modeled protein enriched with branched chain amino acids in Pichia pastoris.
We have earlier in silico designed the 3-dimensional structure of a protein enriched with branched chain amino acids (BCAA, 56.4%), having only α-helical coiled-coil structure. Here, homology modeling was used to improve the in silico designed protein model. The secondary and tertiary structures of improved protein model were predicted, and validated using various online bioinformatics tools. The amino acid sequence of the final predicted Protein Model-51 was EQLTKLEIVIRVLKLLKLIGGLVSLVEWVLTALVTLLGDKVLDDILTDVIMLVKKIL DKVIGIVYVLAILALILSEVLDILWLLEKLVEILEGHHHHHH. The amino acid sequence of the protein model was reverse translated to DNA sequence and codons were optimized using codon optimization tool. The chemically synthesized BCAA51 gene was cloned to pPICZαC vector, and transformed into DH5α E. coli strain. After successful transformation, the protein was expressed in P. pastoris system by inducing with 0.5% methanol, every 24 h for up to 144 h. The expressed protein was purified by His Select Nickel affinity chromatography with an yield of 1.412 mg/L. The recombinant protein was confirmed by SDS-PAGE and western blot analysis, which showed a clear band at the expected molecular weight of ~11 kDa. Thus, here we have shown that the in silico designed protein is successfully cloned and expressed in P. pastoris.


Synergistic effect of counterregulatory hormones during insulin-induced hypoglycemia in rats: participation of lipolysis and gluconeogenesis to hyperglycemia.
To study the synergistic effect of G (glucagon, 0.02 mg.kg-1), H (hydrocortisone, 20 mg.kg-1) and E (phenylephrine + isoproterenol, both 1 mg.kg-1) during insulin-induced hypoglycemia (IIH) in rats with 6 h of food deprivation (F6 group). I (insulin, 1 U.kg-1) was injected i.p. and 30 min later saline (F6 + I group), H, G and E individually or combined (G + H, G + E, H + E and G + H + E) were all injected i.p. and all experiments started 1 h after I injection. The rise in glycemia with H + G + E was greater than the sum of the responses to i.p. H, G and E individually or in double combination plus any single hormone. This effect was reproduced by G + H + Iso (isoproterenol, 1 mg.kg-1), G + H + Iso + Met (metoprolol, 1 mg.kg-1) and G + H + Sal (salbutamol, 1 mg.kg-1). A clear relationship was shown between glycemia and free fatty acids levels. Liver gluconeogenesis from glycerol (2 mmol.L-1) was higher in the group which received G + H + beta-adrenergic agonist vs control rats (F6 or F6 + I groups). (a) Acute hyperglycemia is obtained from a condition of IIH by combined i.p. of G + H + beta-adrenergic agonists; (b) This effect cannot be ascribed to a single hormone, but is a consequence of the combined effects of these substances; (c) Blood insulin levels and liver glycogen have no participation; (d) Lipolysis mediated by a beta-adrenergic mechanism and gluconeogenesis from glycerol contribute to the hyperglycemia.


Naloxone reversal of opioid anesthesia revisited: clinical evaluation and plasma concentration analysis of continuous naloxone infusion after anesthesia with high-dose fentanyl.
In spite of several advantages, the need for postoperative ventilatory support limits the use of high-dose opioid anesthesia. We prospectively evaluated the effectiveness of naloxone infusion for the reversal of high-dose fentanyl anesthesia. Anesthesia was maintained with fentanyl in patients undergoing major abdominal surgery. After anesthesia, the trachea was extubated when intravenous naloxone, which was titrated in separate 50- micro g doses, established an acceptable level of consciousness and arterial blood gas (ABG) status under spontaneous respiration; this was followed by continuous infusion started at the rate of the sum of the bolus doses per hour. The naloxone infusion was terminated based on evaluation of the level of consciousness, ABG, and acute abstinence symptoms. Postoperative pain was evaluated using self-reported four-step categorical terms (none, mild, moderate, and severe). Plasma concentrations of fentanyl and naloxone were analyzed in 12 patients, using high-performance liquid chromatography. Fifty-seven out of 59 eligible patients were successfully extubated at 34 +/- 14 min after termination of fentanyl (total dose, 127 +/- 64 micro g.kg(-1); mean +/- SD) with naloxone (total bolus, 3.4 +/- 2.6 micro g.kg(-1)). All these patients recovered fully without ventilatory support under the naloxone infusion, which was terminated at 11 +/- 7 h. The reduction of the naloxone infusion rate effectively relieved the increased pain, and no supplemental analgesic was used in any patients during the naloxone infusion. Pharmacokinetic analysis did not indicate any correlations between plasma fentanyl and naloxone concentrations. The results suggest that naloxone infusion with individual dose titration facilitates the use of high-dose opioid anesthesia, maintaining the advantager of this anesthesia.


Effect of pyridoxine deficiency on aromatic L-amino acid decarboxylase in adult rat brain.
We have investigated the effect of pyridoxine deficiency on aromatic L-amino acid decarboxylase (AADC) using both dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5HTP) as substrates in the rat brain. The activity ratios of DOPA decarboxylase/5HTP decarboxylase measured under optimal substrate and cofactor concentrations were different in the cerebellum, cerebral cortex, corpus striatum and hypothalamus of the normal rat. In pyridoxine deficiency, there were no parallel decreases in DOPA and 5HTP decarboxylase activities in various brain regions. Dialysis of brain homogenates, in the presence and absence of hydroxylamine, resulted in a total or near total loss of 5HTP decarboxylase activity compared to DOPA decarboxylase activity, indicating that pyridoxal phosphate may be more tightly bound to DOPA decarboxylase than to 5HTP decarboxylase. These results, indicating that pyridoxine deficiency has differential effects on the activity of AADC, are consistent with our earlier observation of non-parallel changes in dopamine and serotonin content in various brain regions of the pyridoxine-deficient rat.


Histopathology of different types of atrophy of the human tongue.
Numerous studies have been devoted to the various histopathologic changes of the surface of the tongue. The muscles of the tongue and their changes in the process of ageing as well as in neurogenic atrophies, however, have not been systematically examined so far. Enlarging upon previous studies, an autopsy material of 170 tongues from all age groups was histologically examined in order to identify the steps in the development of age-related atrophy. These are characterized by a histometrically documented atrophy of the musculature with progressive lipomatosis. Fatty infiltration starts in the 2nd/3rd decade at three sites of predilection: body, root and tip of the tongue in the region of the anterior lingual gland (NUHN). The age-dependent atrophy and the known clinical behaviour of neurogenic atrophies of the tongue are correlated with the histopathology of three typical forms: a neurogenic myasthenic atrophy of the tongue with high-grade symmetrical fatty replacement as an expression of a progressive myasthenic denervation; a lipomatous atrophy of the tongue as a late stage of poliomyelitis and long-term treatment in the "Iron Lung", and a lipomatous hemiatrophy due to posttraumatic extracranial hypoglossus paresis. The paretic part of this tongue consists of 85-90% fatty tissue. The different degrees of muscular atrophy of the tongue are largely compensated by metaplasia of fatty tissue in the perimysium following muscular degeneration (in the sense of a fatty replacement). With the exception of general and severe myasthenic atrophy, size, form and function of the tongue fail to show any significant changes in age-related atrophy and hemiatrophy.


DNA double-strand break repair from head to tail.
DNA double-strand break repair is a complex process that requires multiple enzymatic and structural activities to rejoin or repair the broken DNA ends using one of several repair pathways. These enzymatic and structural activities include end detection, end processing and alignment of DNA ends. Recent structural and functional studies of the DNA double-strand break repair factors Mre11/Rad50, Ku70/80 and Xrcc4 show how these enzymes combine and assemble both enzymatic and structural activities in DNA double-strand break repair.


Diabetic ketoacidosis in Saudi Arabia: factors precipitating initial admission and readmission.
Diabetic ketoacidosis (DKA) is one of the complications of diabetes mellitus (DM), primarily type 1 DM. To our knowledge, only one study explored DKA readmission rates in Saudi Arabia. Identify and analyze precipitating factors for DKA admission and readmission. Medical record review. Tertiary care center. We identified all patients aged 15 years and older admitted with DKA from 2018 to 2020. Descriptive factors and uni-and multivariate analyses are presented for associations with initial admission and readmission. Relationships between precipitating factors and initial admission and readmission. 176 patients. Most of the patients had type 1 DM (n=157). The median (interquartile percentiles) for duration of DM was 6.0 (1.0-12.0) years. The mean (SD) HbA1C (%) was 11.8 (2.6). The factors that precipitated DKA were most commonly treatment nonadherence (55.1%), followed by infections (31.8%) and nonadherence to diet (25.6%). The most common symptoms were nausea and vomiting (87.5%), followed by abdominal pain (72.7%). During the study period, 32.4% of the sample were read-mitted with DKA. The median (interquartile range) duration between the first and second admission was 12 (4-25) weeks. In the multivariate analysis, increased odds of readmission for DKA were associated with type 1 DM and medication nonadherence (P=.038, P=.013, respectively). The severity of the initial DKA and the control of DM were not associated with the readmission rate. Treatment nonadherence is the leading precipitating factor of DKA in our region. Patient education and counseling play a major role in addressing this preventable complication and its medical and financial burden. We advocate more efforts dedicated toward patient education and logistic support. Retrospective-single center. None.


Combined gait analysis and radiologic examination in children with X-linked hypophosphatemia.
X-linked hypophosphataemia causes bone deformities and gait abnormalities that tend to worsen with age in the absence of appropriate treatment. However, doctors do not currently use quantitative tools to characterize these symptoms and their possible interactions. Radiographs and 3D gait data from 43 non-surgical growing children with X-linked hypophosphataemia were acquired prospectively. Data from age-matched typically developing children were used to form the reference group. Subgroups based on radiological parameters were compared with each other and with the reference population. Linear correlations between radiographic parameters and gait variables were examined. X-linked hypophosphatemic patients differed from the control group in pelvic tilt, ankle plantarflexion, knee flexion moment and power. High correlations with tibiofemoral angle were found for trunk lean, knee and hip adduction, and knee abduction moment. The Gait Deviation Index was below 80 for 88% of the patients with a high tibiofemoral angle (varus). Compared to other subgroups, varus patients had augmented trunk lean (+3°) and knee adduction (+10°) and decreased hip adduction (-5°) and ankle plantarflexion (-6°). Femoral torsion was associated with alterations in rotation at the knee, and hip. Gait abnormalities induced in X-linked hypophosphataemia have been described in a large cohort of children. Links between gait alterations and lower limb deformities were found, with varus deformities standing out. Since bony deformities appear when X-linked hypophosphatemic children start walking and have been found to alter gait patterns, we suggest that combining radiology with gait analysis may improve the clinical management of X-linked hypophosphataemia.


Characterization and Quantitative Determination of a Diverse Group of Bacillus subtilis subsp. subtilis NCIB 3610 Antibacterial Peptides.
Five antibacterial peptides produced by Bacillus subtilis NCIB 3610 were purified, quantified, characterized, and identified in the present study. Cell-free extracts were subjected to three purification protocols employing ammonium sulfate or organic solvent precipitation and their combination, followed by ion-exchange chromatography, solid-phase extraction, and preparative high-performance liquid chromatography (HPLC). The combined ammonium sulfate and organic solvent precipitation extraction protocol presented the best results for peptide purification. In the five fractions that presented antimicrobial activity, antibacterial peptides were quantified by the turbidometric method and by HPLC using nisin for external calibration, with the second providing more accurate results. All peptides were pH- and temperature-resistant and their sensitivity to proteases treatment indicated their proteinic nature. The five peptides were subjected to microwave-assisted acid hydrolysis (MAAH) and following derivatization were analyzed using norleucine as the internal standard, to determine their amino acid content. The identification of the isolated peptides using the UniProt and PubChem databases indicated that the four peptides correspond to UniProt entries of the bacteriocins Subtilosin-A (Q1W152) Subtilosin-SbOX (H6D9P4), Ericin B (Q93GH3), Subtilin (P10946), and the fifth to the non-ribosomal antibacterial lipopeptide surfactin (CID:443592). The amino acid content determination and computational analyses, applied in the present work on the antimicrobial peptides of B. subtilis, proved an efficient screening and quantification method of bacteriocins that could potentially be applied in other bacterial strains. The constructed phylogenetic trees heterogeneity observed across the five peptides investigated might be indicative of competitive advantage of the strain.