Robotic management of superior mesenteric artery syndrome.
Robotic surgery is an advanced minimally invasive approach that has become popular over the last decade for its precision and innovative technology. The superior mesenteric artery syndrome is a known but rare cause of duodenal obstruction because of its compression between the superior mesenteric artery and the abdominal aorta. This paper reports and discusses the management of 2 patients who presented with this syndrome and were treated using the robot.


Identification and analysis of LNO1-like and AtGLE1-like nucleoporins in plants.
Nucleoporins (Nups) are building blocks of the nuclear pore complex (NPC) that mediate cargo trafficking between the nucleus and the cytoplasm. Although the physical structure of the NPC is well studied in yeast and vertebrates, little is known about the structure of NPCs or the function of most Nups in plants. Recently we demonstrated two Nups in Arabidopsis: LONO1 (LNO1), homolog of human NUP214 and yeast Nup159, and AtGLE1, homolog of yeast Gle1, are required for early embryogenesis and seed development. To identify LNO1 and AtGLE1 homologs in other plant species, we searched the protein databases and identified 30 LNO1-like and 35 AtGLE1-like proteins from lower plant species to higher plants. Furthermore, phylogenetic analyses indicate that the evolutionary trees of these proteins follow expected plant phylogenies. High sequence homology and conserved domain structure of these nucleoporins suggest important functions of these proteins in nucleocytoplasmic transport, growth and development in plants.


[Effects of gamma interferon (IFN-gamma) and interleukin-1 beta (IL-1 beta) on contractile and relaxing responses of guinea-pig airway strips].
Gamma interferon (IFN-gamma) and interleukin(IL)-1 beta produced by T lymphocytes and macrophages may have significant roles in the airway inflammation seen in bronchial asthma and are known to modify functions of both immune and non-immune cells. In this study, we examined whether the cytokines can modify contractile and relaxing responses of guinea pig airway strips in vitro. The isometric tension of guinea-pig strips was measured in a tissue bath filled with Krebs-Henseleit solution. Contracting responses to carbachol and KCl, and the relaxing response to isoproterenol (ISO) were examined. Effects of the cytokines were examined by comparing responses of the strips incubated with or without IFN-gamma (1,000 U/ml, 25,000 U/ml) and IL-1 beta (25 ng/ml, 250 ng/ml). Contracting responses to carbachol and KCl were not affected by the incubation with IFN-gamma but slightly increased in maximum contraction by carbachol after 5 hours incubation with 25,000 U/ml of IFN-gamma. Both 1- and 5-hour incubation of the strips with 250 ng/ml of IL-1 beta significantly decreased the sensitivity to KCl without affecting maximum contraction. 1- and 5-hour incubation of the strips with 25,000 U/ml of IFN-gamma or 250 ng/ml of IL-1 beta significantly increased or decreased the sensitivity to ISO without affecting maximum relaxation, respectively. Denudation of epithelium from the strips completely abolished the effects of the cytokines on KCl and ISO responses. In addition, the effects of IFN-gamma on ISO relaxation and IL-1 beta on KCl contraction were abolished by indomethacin but not by N omega-nitro-L-arginine methyl ester (N omega-NAME). The effect of IL-1 beta on ISO was inhibited both by indomethacin and by N omega-NAME. These results suggest that IFN-gamma and IL-1 beta may modify airway smooth muscle responses through their effects on airway epithelium by inducing the release of prostanoids and/or nitric oxide.


[Hepatocellular carcinoma with extrahepatic malignancies].
A clinical investigation of 16 hepatocellular carcinoma (HCC) patients with extrahepatic malignancies (13 male, 3 female) has been conducted. The age of these patients ranged from 55 to 76 years. Three of these double cancer cases were hemocronous, and 13 were heterochronous. The duration between the occurrence of the cancers ranged from 2 years and 4 months to 22 years. As for the site of the other cancer, the stomach was the most common organ (12 cases). In nine cases out of 16, the HCC was resected, whereas the other cases were treated with a TAE and hepatic artery ligation because the cancer were far advanced stages. Early detection of an HCC by AFP or an ultrasonographic examination, and a subsequent surgical resection in cases of a postoperative cancer patient with a liver dysfunction may lead to a more favorable prognosis.


Determination of the hyperfine magnetic field in magnetic carbon-based materials: DFT calculations and NMR experiments.
The prospect of carbon-based magnetic materials is of immense fundamental and practical importance, and information on atomic-scale features is required for a better understanding of the mechanisms leading to carbon magnetism. Here we report the first direct detection of the microscopic magnetic field produced at (13)C nuclei in a ferromagnetic carbon material by zero-field nuclear magnetic resonance (NMR). Electronic structure calculations carried out in nanosized model systems with different classes of structural defects show a similar range of magnetic field values (18-21 T) for all investigated systems, in agreement with the NMR experiments. Our results are strong evidence of the intrinsic nature of defect-induced magnetism in magnetic carbons and establish the magnitude of the hyperfine magnetic field created in the neighbourhood of the defects that lead to magnetic order in these materials.


Slight but significant improvement of insulin resistance of Wistar fatty rats by treatment with a disaccharidase inhibitor, AO-128.
To know whether the insulin resistance is improved by delaying carbohydrate absorption from the small intestine, we studied the effect of a disaccharidase inhibitor, AO-128, on insulin resistance of Wistar fatty rats. Rats were kept on standard laboratory chow with and without 10 ppm of AO-128 for 4 weeks, and then subjected to the glucose clamp. At the end of the 4-week treatment, plasma glucose level at 14:00 to 16:00 of AO-128 treated rats was 121 +/- 14 mg/100 ml (mean +/- S.D.), significantly lower than 226 +/- 72 mg/100 ml of the rats without AO-128. During clamp steady state under 20 mU.kg (-1).min (-1) continuous insulin infusion, glucose uptake of AO-128 treated rats was only 7.62 +/- 0.70 mg.kg (-1). min (-1), not different from 6.64 +/- 0.91 mg.kg (-1).min (-1) of rats without AO-128, but much lower than the lean littermates (20.81 +/- 3.11 mg.kg (-1).min (-1)). However, the percent suppression of hepatic glucose output was 55.2 +/- 23.8%, which, though incomplete, was significantly higher than 17.4 +/- 11.2% of rats without AO-128. The present study suggested that there were at least two, components of insulin resistance, a genetically determined and a poor-glycemic control-related, and that the latter insulin resistance was ameliorated by AO-128.


Novel imaging in renal cell carcinoma.
Renal cell carcinoma is a heterogeneous disease with a spectrum of subtypes and clinical behavior. Quantitative and qualitative imaging biomarkers are sought to correlate with genetic and histologic features and complement pathologic analysis. Texture analysis, radiogenomics, and modality-specific advancements have yielded an array of renal cell carcinoma imaging biomarkers in the research domain. Although many techniques are promising, standardization and validation of these procedures are needed prior to implementation into clinical practice. We introduce novel imaging techniques and analytic methods which have been shown to contribute to characterization of renal cell carcinoma and its subtypes, aggressiveness, and responsiveness to therapy, including associated advantages and limitations.


Vesicle budding induced by binding of curvature-inducing proteins.
Vesicle budding induced by protein binding that generates an isotropic spontaneous curvature is studied using a mean-field theory. Many spherical buds are formed via protein binding. As the binding chemical potential increases, the proteins first bind to the buds and then to the remainder of the vesicle. For a high spontaneous curvature and/or high bending rigidity of the bound membrane, it is found that a first-order transition occurs between a small number of large buds and a large number of small buds. These two states coexist around the transition point. The proposed scheme is simple and easily applicable to many interaction types, so we investigate the effects of interprotein interactions, the protein-insertion-induced changes in area, the variation of the saddle-splay modulus, and the area-difference-elasticity energy. The differences in the preferred curvatures for curvature sensing and generation are also clarified.


The Diagnosis and Natural History of Multiple System Atrophy, Cerebellar Type.
The objective of this study was to identify key features differentiating multiple system atrophy cerebellar type (MSA-C) from idiopathic late-onset cerebellar ataxia (ILOCA). We reviewed records of patients seen in the Massachusetts General Hospital Ataxia Unit between 1992 and 2013 with consensus criteria diagnoses of MSA-C or ILOCA. Twelve patients had definite MSA-C, 53 had possible/probable MSA-C, and 12 had ILOCA. Autonomic features, specifically urinary urgency, frequency, and incontinence with erectile dysfunction in males, differentiated MSA-C from ILOCA throughout the disease course (p = 0.005). Orthostatic hypotension developed later and differentiated MSA-C from ILOCA (p < 0.01). REM sleep behavior disorder (RBD) occurred early in possible/probable MSA-C (p < 0.01). Late MSA-C included pathologic laughing and crying (PLC, p < 0.01), bradykinesia (p = 0.01), and corticospinal findings (p = 0.01). MRI distinguished MSA-C from ILOCA by atrophy of the brainstem (p < 0.01) and middle cerebellar peduncles (MCP, p = 0.02). MSA-C progressed faster than ILOCA: by 6 years, MSA-C walker dependency was 100 % and ILOCA 33 %. MSA-C survival was 8.4 ± 2.5 years. Mean length of ILOCA illness to date is 15.9 ± 6.4 years. A sporadic onset, insidiously developing cerebellar syndrome in midlife, with autonomic features of otherwise unexplained bladder dysfunction with or without erectile dysfunction in males, and atrophy of the cerebellum, brainstem, and MCP points strongly to MSA-C. RBD and postural hypotension confirm the diagnosis. Extrapyramidal findings, corticospinal tract signs, and PLC are helpful but not necessary for diagnosis. Clarity in early MSA-C diagnosis can prevent unnecessary investigations and facilitate therapeutic trials.


SIKVAV-Modified Chitosan Hydrogel as a Skin Substitutes for Wound Closure in Mice.
Skin wound healing is a complex and dynamic process that involves angiogenesis and growth factor secretion. Newly formed vessels can provide nutrition and oxygen for skin wound healing. Growth factors in skin wounds are important for keratinocytes and fibroblasts proliferation, epithelialization, extracellular matrix remodeling, and angiogenesis, which accelerate skin wound healing. Therefore, treatment strategies that enhance angiogenesis and growth factors secretion in skin wounds can accelerate skin wound healing. This study investigated the effects of a SIKVAV (Ser-Ile-Lys-Val-Ala-Val) peptide-modified chitosan hydrogel on skin wound healing. Hematoxylin and eosin (H&E) staining demonstrated that the SIKVAV-modified chitosan hydrogel accelerated the re-epithelialization of wounds compared with that seen in the negative and positive controls. Masson's trichrome staining showed that more collagen fibers were deposited in the skin wounds treated with the SIKVAV-modified chitosan hydrogel than in the negative and positive controls. Immunohistochemistry assays demonstrated that more myofibroblasts were deposited and more angiogenesis occurred in skin wounds treated with the SIKVAV-modified chitosan hydrogel than in the negative and positive controls. In addition, ELISA assays showed that the SIKVAV-modified chitosan hydrogels promoted the secretion of growth factors in skin wounds. Taken together, these results suggest that the SIKVAV-modified chitosan hydrogel has the potential to be developed as synthesized biomaterials for the treatment of skin wounds.


Three-dimensional evaluation of postural stability in Parkinson's disease with mobile technology.
Postural instability is a hallmark of Parkinson's disease. Objective metrics to characterize postural stability are necessary for the development of treatment algorithms to aid in the clinical setting. The aim of this project was to validate a mobile device platform and resultant three-dimensional balance metric that characterizes postural stability. A mobile Application was developed, in which biomechanical data from inertial sensors within a mobile device were processed to characterize movement of center of mass in the medial-lateral, anterior-posterior and trunk rotation directions. Twenty-seven individuals with Parkinson's disease and 27 age-matched controls completed various balance tasks. A postural stability metric quantifying the amplitude (peak-to-peak) of sway acceleration in each movement direction was compared between groups. The peak-to-peak value in each direction for each individual with Parkinson's disease across all trials was expressed as a normalized value of the control data to identify individuals with severe postural instability, termed Cleveland Clinic-Postural Stability Index. In all conditions, the balance metric for peak-to-peak was significantly greater in Parkinson's disease compared to controls (p < 0.01 for all tests). The balance metric, in conjunction with mobile device sensors, provides a rapid and systematic metric for quantifying postural stability in Parkinson's disease.


Antimyeloma activity of bromodomain inhibitors on the human myeloma cell line U266 by downregulation of MYCL.
Bromodomain and extraterminal protein (BET) inhibitors suppress the expression of c-MYC. U266, a human myeloma cell line, expresses the MYCL gene, but not the c-MYC gene. Our aim was to analyse the antimyeloma activity of BET inhibitors on U266 cells. Two BET inhibitors, I-BET151 and JQ1, were tested. U266 cell proliferation decreased to 61.5 and 54.0% of the control after incubation with 500 nmol/l I-BET151 for 72 and 96 h and to 53.5 and 56.4% of control after incubation with 500 nmol/l JQ1 for 72 and 96 h by MTS tetrazolium, respectively. BET inhibitors induced cell cycle arrest at the G1 phase in U266 cells, but did not induce apoptosis by flow cytometry. According to Gene Set Enrichment Analysis, MYC-related genes were significantly downregulated in U266 cells treated with I-BET151 similar to KMS11 cells that expressed c-MYC. The MYCL1 was expressed in U266 cells, whereas c-MYC and MYCN were not by quantitative real-time reverse-transcription-PCR. Incubation with I-BET151 induced downregulation of MYCL1 in U266 cells. BET inhibitors decreased the cell proliferation in U266 cells with overexpression of MYCL less than those without overexpression of MYCL. BET inhibitors induce G1 arrest without apoptosis and interfere with the proliferation of U266 myeloma cells, which express MYCL, but not c-MYC. BET inhibitors might be active in cancers that express MYCL, but not c-MYC.


Determination of thiorphan, a racecadotril metabolite, in human plasma by LC-MS/MS and its application to a bioequivalence study in Chinese subjects .
The objective of this study was to use LC-MS/MS to compare the pharmacodynamic properties and bioequivalence of two 200-mg formulations of racecadotril: suspension formulation (test) and granule formulation (reference) in healthy Chinese subjects. A single-dose, randomized, two-period crossover study was conducted in fasted healthy Chinese subjects, who received a single oral dose of the test or reference formulation, followed by a 7-day washout period and administration of the alternate formulation. The rapid and highly sensitive LC-MS/MS method exhibited a reasonable linearity range (2.324 - 952.000 ng/mL) and high sensitivity (LLOQ of 2.324 ng/mL). The within- and between-run precision, accuracy, and stability results were within the acceptable limits, and no matrix effect was observed. The 90% CI of the ratio of geometric means for AUC0-t, AUC0-∞, and Cmax were 88.1 - 102.3%, 87.9 - 101.5% and 99.5 - 113%, respectively, which met the regulatory criteria for bioequivalence. The method is suitable for quantification of thiorphan in human plasma. In addition, the results indicated that the test and reference formulations were bioequivalent in terms of both rate and extent of absorption.


Prospective memory and executive function in schizophrenia.
Experimental studies of normal subjects have shown that the intention to perform an action speeds word recognition for items related to that intention (Goschke & Kuhl, 1993). This phenomenon--the intention superiority effect (ISE)--is thought to be mediated by frontal executive functions. Since schizophrenia is characteristically associated with forms of frontal-executive dysfunction, an impaired ISE might be expected in this patient group. A script-learning paradigm was used to investigate the ISE in 10 schizophrenics who do show evidence of executive dysfunction and in 10 who do not. As predicted, only the former showed an ISE; however, all schizophrenics showed an ISE to words semantically related to the intention. It seems that the ability to form specific intentions is impaired only in schizophrenics with executive dysfunction; however, they retain the ability to form more generalized intentions.


Hybrid Density Functional Tight Binding (DFTB)─Molecular Mechanics Approach for a Low-Cost Expansion of DFTB Applicability.
The density functional-based tight binding (DFTB) method has seen a rise in adoption for materials modeling, as it offers significant improvement in scalability with accuracy comparable to the density functional theory (DFT) when good parameterizations exist. The cost reduction in DFTB compared to DFT is achieved by the pre-parameterization of the elements of the Hamiltonian matrix as well as the repulsion potential between all pairs of atoms. Parameterization for new systems with accuracies competitive with DFT in specific applications requires specialized manpower and computational resources. This prevents the application of the DFTB method to systems for which it was not parameterized. In this work, we explore an approach to address the problem of missing parameters of DFTB by modeling the interactions with missing Slater-Koster parameters with an interatomic interaction potential. When the distance between two atoms modeled at the force-field level is sufficiently large, the approach results in accurate structural and electronic properties. The resulting calculation is therefore a hybrid between DFTB and molecular mechanics, a pure DFTB for atoms with a complete set of interatomic parameterizations, and a mix between DFTB and molecular mechanics for atoms with a missing interatomic parameterization. The approach is expected to be particularly useful for hybrid materials and interfaces. The method is tested on the examples of 2D materials, mixed oxides, and a large-scale calculation of an oxide-oxide interface.


Corrosion resistance of the soldering joint of post-soldering of palladium-based metal-ceramic alloys.
To evaluate the corrosion resistance of post soldering of metal-ceramic alloys, four commercially available palladium-system metal-ceramic alloys (Pd-Cu, Pd-Ni, Pd-Ag, and Pd-Sb systems) and two types of solder (12 k gold solder and 16 k gold solder) with different compositions and melting points were used. The corrosion resistance of the soldered joint was evaluated by anodic polarization. The electrochemical characteristics of soldered surface were measured using electrochemical equipment. Declines in corrosion resistance were not detectable with Pd-Cu, Pd-Ag and Pd-Sb types, but break down at low potential occurred with Pd-Ni type.


A One-Sided Affair: Unoriginal Origin of the Left Coronary Artery, a Case Report.
Coronary artery anomalies constitute a group of congenital malformations that have a multitude of clinical manifestations and highly variable pathophysiology. We report a 56-year-old male with angina due to an anomalous origin of the left main coronary artery; approach and management.


[Reciprocal relationships between orthodontics and periodontics: relevance of a synergistic action].
The aim of this article is to review evidence on the reciprocal relationships between orthodontics and periodontics. Normal intra-arch and inter-arch relationships have long been considered as an anatomic prerequisite for the preservation of dental health and function. Certain malocclusion traits are associated with difficulties in maintaining good oral hygiene and as a consequence to poor periodontal condition. Therefore, proper alignment of the teeth provided by orthodontic treatment may promote good control of soft deposit and calculus and subsequent periodontal inflammation. The tendency of orthodontic appliances, particularly the brackets and bands to promote the accumulation of plaque and thus increasing the risk of developing localized periodontal disease must however be constantly emphasized. Periodontitis involves progressive loss of the alveolar bone around the teeth, pathological tooth migration and gingival recession with pathological tooth migration and gingival recession as a possible outcome. The effectiveness of orthodontics in conjunction with periodontics in the management of these esthetic and functional defects is highlighted in this review.


Reversed-phase partition thin-layer chromatography of rat liver lecithins to yield eight simple phosphatidyl cholines.
The four fractions obtained by argentation thin-layer chromatography of intact rat liver lecithins can be further subdivided by reversed-phase partition thin-layer chromatography on hydrophobic kieselguhr. The resultant eight fractions contain virtually only one saturated and one unsaturated acid each.


Markers of microbial translocation predict hypertension in HIV-infected individuals.
The aim of the study was to test the hypothesis that microbial translocation, quantified by levels of lipopolysaccharide (LPS) and subsequent monocyte activation [soluble (sCD14)], is associated with hypertension in HIV-infected individuals. In this exploratory substudy, 42 patients were recruited from a larger, longitudinal HIV-infected cohort study on blood pressure. LPS and sCD14 levels were measured retrospectively at the time of nadir CD4 cell count, selecting untreated HIV-infected patients with both advanced immunodeficiency and preserved immunocompetence at the time of nadir. Patients with later sustained hypertension (n = 16) or normotension (n = 26) throughout the study were identified. LPS was analysed using the Limulus Amebocyte Lysate colorimetric assay (Lonza, Walkersville, MD) and sCD14 using an enzyme-linked immunosorbent assay (ELISA). Nonparametric statistical tests were applied. In the HIV-infected patients [median (interquartile range) age 42 (32-46) years; 79% male and 81% Caucasian], LPS and sCD14 levels were both negatively correlated with nadir CD4 cell count. Plasma levels of LPS (P < 0.001) and sCD14 (P = 0.024) were elevated in patients with later hypertension compared with patients with normotension. There was a stepwise increase in the number of patients with hypertension across tertiles of LPS (P = 0.001) and sCD14 (P = 0.007). Both LPS and sCD14 were independent predictors of elevated blood pressure after adjustment for age and gender. For each 10-unit increase in LPS (range 66-272 pg/ml), the increment in mean blood pressure in the first period of blood pressure recording was 0.86 (95% confidence interval 0.31-1.41) mmHg (P = 0.003). As LPS and sCD14 were both independently associated with elevated blood pressure, microbial translocation may be linked to the development of hypertension.


Microsurgical replantation of sexual organs in three patients.
The present study deals with microsurgical replantation technique. The technique was applied in 3 patients whose sexual organs had been accidentally cut off. Necrosis of the sutured organs occurred in 2 cases. In 1 case, however, healing with proper miction and sexual function was achieved. Prolonged period (over 12 hours) from the accident to operation as well as the extensive injury of tissues with the vascular system crush were considered to be the main reason for failure. Microsurgical reconstruction of penis and testes with the use of vessel grafts prolonged the hypoxia which led to necrosis. Disturbances in vein blood outflow from the sutured organs contributed to this process as well. The third case resulted in success mostly due to quick intervention (5 h from injury) as well as to proper microsurgical reconstruction of vessels, nerves, and urethra. In addition suprapubic urine diversion was successfully applied and the urethra healed on the perforated catheter. Routine antibiotics as well as antithrombotic prophylactics were administered in all of the 3 cases.


Metasurfaced Reverberation Chamber.
The concept of metasurfaced reverberation chamber (RC) is introduced in this paper. It is shown that by coating the chamber wall with a rotating 1-bit random coding metasurface, it is possible to enlarge the test zone of the RC while maintaining the field uniformity as good as that in a traditional RC with mechanical stirrers. A 1-bit random coding diffusion metasurface is designed to obtain all-direction backscattering under normal incidence. Three specific cases are studied for comparisons, including a (traditional) mechanical stirrer RC, a mechanical stirrer RC with a fixed diffusion metasurface, and a RC with a rotating diffusion metasurface. Simulation results show that the compact rotating diffusion metasurface can act as a stirrer with good stirring efficiency. By using such rotating diffusion metasurface, the test region of the RC can be greatly extended.


Validity and reliability of food security measures.
This paper reviews some of the existing food security indicators, discussing the validity of the underlying concept and the expected reliability of measures under reasonably feasible conditions. The main objective of the paper is to raise awareness on existing trade-offs between different qualities of possible food security measurement tools that must be taken into account when such tools are proposed for practical application, especially for use within an international monitoring framework. The hope is to provide a timely, useful contribution to the process leading to the definition of a food security goal and the associated monitoring framework within the post-2015 Development Agenda.


Wiskott-Aldrich syndrome mutation in two Turkish siblings with X-linked thrombocytopenia.
Wiskott-Aldrich syndrome (WAS) is a clinical condition characterized by thrombocytopenia, eczema, and life-threatening infections. In some cases autoimmunity-related problems and even malignancy might be seen; however, some patients have milder clinical manifestations due to mutations in the same gene family, such as in X-linked thrombocytopenia (XLT), which is generally not associated with serious symptoms of disease, except for thrombocytopenia. Herein we report 2 siblings with chronic thrombocytopenia that were diagnosed with XLT based on a missense mutation in the WASP gene (223G>A, Val75Met). To the best of our knowledge this mutation has not been previously reported in a Turkish patient with XLT.


The relationship between critical thinking and decision-making in respiratory care students.
Respiratory therapists evaluate the condition of their patients, make decisions about the appropriateness of the treatment plan, provide care, and evaluate the outcomes of their decisions. To practice effectively they must think critically and make appropriate decisions. As educators make curriculum changes to improve students' decision-making (DM) skills, strategies to develop critical thinking (CT) have been proposed as one method of achieving that goal. This approach is based on the hypothesis that a positive relationship exists between DM and CT. The present study examines the relationship between CT and DM in respiratory care students. If there is a positive relationship between CT and DM, respiratory care training programs might improve the DM skills of future practitioners by providing instruction that improves CT. Using a correlational research design, DM scores from the Clinical Simulation Self-Assessment Examination (CSSAE) were compared with scores from the Watson-Glaser Critical Thinking Appraisal for 143 graduating respiratory care students from 10 programs. Program directors completed a questionnaire and were then interviewed about the methods they employ to develop CT and DM in their students. A significant correlation between CT and DM was found for 110 students completing the Secure Form of the CSSAE (r = 0.32, p < 0.01). All programs used case studies and clinical simulations, and most used role modeling, computer-assisted instruction, patient rounds, small group discussion, and study skills courses. No differences were identified in the use of the CT and DM development strategies by different programs. The findings support the belief that students with strong CT proficiency make better clinical decisions. Assessment of CT proficiency could be used as one part of a process for evaluating prospective students and faculty for respiratory care programs. Program directors and faculty felt that case studies and clinical simulations are important strategies.


High-Frequency Oscillations in Tumor-Related Epilepsy.
To define the patient characteristics, tumor characteristics, and clinical course of patients with primary brain tumors with high-frequency oscillations (HFOs) recorded on electrocorticography. Furthermore, we evaluated whether the presence of HFOs portends a greater risk of postoperative tumor-related epilepsy and whether the resection of HFO-generating tissue reduces likelihood of postoperative tumor-related epilepsy. This was a retrospective study of 35 patients undergoing awake craniotomy for tumor resection, all of whom underwent intraoperative electrocorticography. Electrocorticography data were reviewed to assess the presence of HFOs and determine their contact locations. The data were analyzed to determine whether HFO-generating tissue was included in the resection and relationship to postoperative seizure outcome. Seventeen patients (48.5%) were found to have HFOs. Very few patients (4 of 35, 11.4%) had sharp waves. Patients with and without HFOs did not significantly differ in demographics, presentation, tumor characteristics, or tumor molecular genetics. A history of seizures prior to resection was not associated with the presence of HFOs ( P = 0.62), although when patients had seizures during the same hospitalization as the resection, HFOs were more likely to be present ( P = 0.045). Extent of HFO resection was not associated with the likelihood of postoperative seizure freedom. Approximately half (48.5%) of patients undergoing resection for a primary brain tumor had HFOs. Although HFO resection was not shown to lead to improved seizure freedom, this study was limited by a small sample size, and further investigation into HFO resection and patient outcomes in this population is warranted.


Status epilepticus after baclofen withdrawal.
Baclofen is widely used in the treatment of spasticity of spinal origin. It is relatively free of side effects or toxic actions on the nervous system or other organs. Agitation, personality change, and auditory and visual hallucinations have been described following its abrupt withdrawal. One patient with generalized seizures and one with complex partial seizures after baclofen withdrawal have been reported. This paper presents a patient who developed status epilepticus after baclofen withdrawal, and who sustained hypoxic cerebral injury. This observation further emphasizes the possibility of infrequent complications of baclofen therapy, and the advisability of gradual changes in baclofen dosage.


Identification of a Cyanobacterial RND-Type Efflux System Involved in Export of Free Fatty Acids.
An RND (resistance-nodulation-division)-type transporter having the capacity to export free fatty acids (FFAs) was identified in the cyanobacterium Synechococcus elongatus strain PCC 7942 during characterization of a mutant strain engineered to produce FFAs. The basic strategy for construction of the FFA-producing mutant was a commonly used one, involving inactivation of the endogenous acyl-acyl carrier protein synthetase gene (aas) and introduction of a foreign thioesterase gene ('tesA), but a nitrate transport mutant NA3 was used as the parental strain to achieve slow, nitrate-limited growth in batch cultures. Also, a nitrogen-regulated promoter PnirA was used to drive 'tesA to maximize thioesterase expression during the nitrate-limited growth. The resulting mutant (dAS2T) was, however, incapable of growth under the conditions of nitrate limitation, presumably due to toxicity associated with FFA overproduction. Incubation of the mutant culture under the non-permissive conditions allowed for isolation of a pseudorevertant (dAS2T-pr1) capable of growth on nitrate. Genome sequence and gene expression analyses of this strain suggested that expression of an RND-type efflux system had rescued growth on nitrate. Targeted inactivation of the RND-type transporter genes in the wild-type strain resulted in loss of tolerance to exogenously added FFAs including capric, lauric, myristic, oleic and linolenic acids. Overexpression of the genes in dAS2T, on the other hand, enhanced FFA excretion and cell growth in nitrate-containing medium, verifying that the genes encode an efflux pump for FFAs. These results demonstrate the importance of the efflux system in efficient FFA production using genetically engineered cyanobacteria.


A transgenic mouse model with inducible Tyrosinase gene expression using the tetracycline (Tet-on) system allows regulated rescue of abnormal chiasmatic projections found in albinism.
Congenital defects in retinal pigmentation, as in oculocutaneous albinism Type I (OCA1), where tyrosinase is defective, result in visual abnormalities affecting the retina and pathways into the brain. Transgenic animals expressing a functional tyrosinase gene on an albino genetic background display a correction of all these abnormalities, implicating a functional role for tyrosinase in normal retinal development. To address the function of tyrosinase in the development of the mammalian visual system, we have generated a transgenic mouse model with inducible expression of the tyrosinase gene using the tetracycline (TET-ON) system. We have produced two types of transgenic mice: first, mice expressing the transactivator rtTA chimeric protein under the control of mouse tyrosinase promoter and its locus control region (LCR), and; second, transgenic mice expressing a mouse tyrosinase cDNA construct driven by a minimal promoter inducible by rtTA in the presence of doxycycline. Inducible experiments have been carried out with selected double transgenic mouse lines. Tyrosinase expression has been induced from early embryo development and its impact assessed with histological and biochemical methods in heterozygous and homozygous double transgenic individuals. We have found an increase of tyrosinase activity in the eyes of induced animals, compared with littermate controls. However, there was significant variability in the activation of this gene, as reported in analogous experiments. In spite of this, we could observe corrected uncrossed chiasmatic pathways, decreased in albinism, in animals induced from their first gestational week. These mice could be instrumental in revealing the role of tyrosinase in mammalian visual development.


Mutation of the sialyltransferase S-sialylmotif alters the kinetics of the donor and acceptor substrates.
Protein sequence analysis of the cloned sialyltransferase gene family has revealed the presence of two conserved protein motifs in the middle of the lumenal catalytic domain, termed L-sialylmotif and S-sialylmotif. In our previous study (Datta, A. K., and Paulson, J. C. (1995) J. Biol. Chem. 270, 1497-1500) the larger L-sialylmotif of ST6Gal I was analyzed by site-directed mutagenesis, which provided evidence that it participates in the binding of the CMP-NeuAc, a common donor substrate for all the sialyltransferases. However, none of the mutants tested in this motif had any significant effect on their binding affinities toward the acceptor substrate asialo alpha1-acid glycoprotein. In this study, we have investigated the role of the S-sialylmotif of the same enzyme ST6Gal I. In total, nine mutants have been constructed by changing the conserved amino acids of this motif to mostly alanine by site-directed mutagenesis. Kinetic analysis for the mutants which retained sialyltransferase activity showed that the mutations in the S-sialylmotif caused a change of Km values for both the donor and the acceptor substrates. Our results indicated that this motif participates in the binding of both the substrates. A sequence homology search also supported this finding, which showed that the downstream amino acid sequence of the S-sialylmotif is conserved for each subgroup of this enzyme family, indicating its association with the acceptor substrate.


Functional and structural characteristics of methylmalonyl-CoA mutase from Pyrococcus horikoshii.
Methylmalonyl-CoA mutase (MCM) requires 5'-deoxyadenosylcobalamin (AdoCbl) as a cofactor and is widely distributed in organisms from bacteria and animals. Although genes encoding putative MCMs are present in many archaea, they are separately encoded in large and small subunits. The large and small subunits of archaeal MCM are similar to the catalytic and AdoCbl-binding domains of human MCM, respectively. In Pyrococcus horikoshii OT3, putative genes PH1306 and PH0275 encode the large and small subunits, respectively. Because information on archaeal MCM is extremely restricted, we examined the functional and structural characteristics of P. horikoshii MCM. Reconstitution experiments using recombinant PH0275 and PH1306 showed that these proteins assemble in equimolar ratios and form of heterotetrameric complexes in the presence of AdoCbl. Subsequent immunoprecipitation experiments using anti-PH0275 and anti-PH1306 antibodies suggested that PH0275 and PH1306 form a complex in P. horikoshii cells in the presence of AdoCbl.


The Valdostana goat: a genome-wide investigation of the distinctiveness of its selective sweep regions.
The Valdostana goat is an alpine breed, raised only in the northern Italian region of the Aosta Valley. This breed's main purpose is to produce milk and meat, but is peculiar for its involvement in the "Batailles de Chèvres," a recent tradition of non-cruel fight tournaments. At both the genetic and genomic levels, only a very limited number of studies have been performed with this breed and there are no studies about the genomic signatures left by selection. In this work, 24 unrelated Valdostana animals were screened for runs of homozygosity to identify highly homozygous regions. Then, six different approaches (ROH comparison, Fst single SNPs and windows based, Bayesian, Rsb, and XP-EHH) were applied comparing the Valdostana dataset with 14 other Italian goat breeds to confirm regions that were different among the comparisons. A total of three regions of selection that were also unique among the Valdostana were identified and located on chromosomes 1, 7, and 12 and contained 144 genes. Enrichment analyses detected genes such as cytokines and lymphocyte/leukocyte proliferation genes involved in the regulation of the immune system. A genetic link between an aggressive challenge, cytokines, and immunity has been hypothesized in many studies both in humans and in other species. Possible hypotheses associated with the signals of selection detected could be therefore related to immune-related factors as well as with the peculiar battle competition, or other breed-specific traits, and provided insights for further investigation of these unique regions, for the understanding and safeguard of the Valdostana breed.


Alignment-free characterization of polarizing beamsplitters.
Traditional methods for measurement of polarizing beamsplitter (PBS) parameters, especially the extinction ratio, require highly polarized light sources, alignment procedures, and/or experimental parameters that change over time, such as polarization rotations. In this work, a new method is presented that employs unpolarized light and a Faraday mirror. It is shown that precise extinction ratio and insertion loss values can be achieved in three single-sweep measurements without any alignment requirements or time-varying signals of any kind.


Upregulating Lin28a Promotes Axon Regeneration in Adult Mice with Optic Nerve and Spinal Cord Injury.
Severed CNS axons fail to regenerate in adult mammals and there are no effective regenerative strategies to treat patients with CNS injuries. Several genes, including phosphatase and tensin homolog (PTEN) and Krüppel-like factors, regulate intrinsic growth capacity of mature neurons. The Lin28 gene is essential for cell development and pluripotency in worms and mammals. In this study, we evaluated the role of Lin28a in regulating regenerative capacity of diverse populations of CNS neurons in adult mammals. Using a neuron-specific Thy1 promoter, we generated transgenic mice that overexpress Lin28a protein in multiple populations of projection neurons, including corticospinal tracts and retinal ganglion cells. We demonstrate that upregulation of Lin28a in transgenic mice induces significant long distance regeneration of both corticospinal axons and the optic nerve in adult mice. Importantly, overexpression of Lin28a by post-injury treatment with adeno-associated virus type 2 (AAV2) vector stimulates dramatic regeneration of descending spinal tracts and optic nerve axons after lesions. Upregulation of Lin28a also enhances activity of the Akt signaling pathway in mature CNS neurons. Therefore, Lin28a is critical for regulating growth capacity of multiple CNS neurons and may become an important molecular target for treating CNS injuries.


[Carrier detection of Glanzmann's thrombasthenia by Taq I restriction fragment length polymorphism of GPIIIa gene].
Glanzmann's thrombasthenia (GT) is an autosomal recessive bleeding disorder in which platelets fail to aggregate in second hemostasis due to qualitative and/or quantitative defect in their GPIIb/IIIa complex. In the present study, both phenotypic and genotypic assays were performed by Western blot and Southern blot techniques in 13 members of 3 GT families. 2 GT carriers of 3 probable carriers whose clinical features and GPIIb/IIIa protein were essentially normal were determined by Taq I/5' GPIIIa RFLP. There were no major deletion or insertion in GPIIIa gene in 4 patients with GT. Thus, the genetic defects in these patients is most likely due to a small change or point mutation in the nucleotide sequence of GPIIIa coding region.


Epidemiological Characteristics, Risk Factors, and Preventive Measures of Occupational Injuries Among Commercial Couriers in China Before and During the COVID-19 Pandemic.
In this study, we focus on the significant upward trend of occupational accidental traffic injuries in commercial couriers during the coronavirus disease (COVID-19) pandemic. This review comments on the characteristics of occupational accidental injuries of commercial couriers in China and then discusses the reasons of the high incidence rate and associated risk factors. Various potential protective measures were also explored to prevent and control the occupational injuries in this vulnerable worker group.


Abnormalities in A-to-I RNA editing patterns in CNS injuries correlate with dynamic changes in cell type composition.
Adenosine to Inosine (A-to-I) RNA editing is a co- or post-transcriptional mechanism that modifies genomically encoded nucleotides at the RNA level. A-to-I RNA editing is abundant in the brain, and altered editing levels have been reported in various neurological pathologies and following spinal cord injury (SCI). The prevailing concept is that the RNA editing process itself is dysregulated by brain pathologies. Here we analyzed recent RNA-seq data, and found that, except for few mammalian conserved editing sites, editing is significantly higher in neurons than in other cell populations of the brain. We studied A-to-I RNA editing in stab wound injury (SWI) and SCI models and showed that the apparent under-editing observed after injury correlates with an approximately 20% reduction in the relative density of neurons, due to cell death and immune cell infiltration that may account for the observed under-editing. Studies of neuronal and astrocyte cultures and a computational analysis of SCI RNA-seq data further supported the possibility that a reduction in neuronal density is responsible for alterations in the tissue-wide editing patterns upon injury. Thus, our data suggest that the case for a mechanistic linkage between A-to-I RNA editing and brain pathologies should be revisited.


Occlusal tooth wear in patients of a dental school's prosthodontic department in Xi'an, China.
To assess the relationships between occlusal tooth wear and occlusal conditions, chewing side preference, and occlusal guidance scheme. A total of 257 Chinese adult dental school patients were categorized according to a hierarchical functional classification system. Occlusal tooth wear was assessed using a modified Smith and Knight index. Occlusal tooth wear index (OTWI) scores were analyzed using multivariate regression models, including four specific occlusal conditions (≥10 teeth in each arch, complete anterior regions, sufficient premolar regions, and sufficient molar regions) adjusted for age and sex. Occlusal tooth wear was observed in all participants; older participants and men had significantly higher mean OTWI scores. The occlusal condition of having fewer than 10 teeth in each arch was significantly associated with occlusal tooth wear; participants with fewer than 10 teeth in each arch had higher mean OTWI scores in anterior and premolar teeth. OTWI scores for the different tooth types were highly correlated with chewing side preference. OTWI scores for the molar region (including third molars) were significantly higher at the preferred chewing side. The same effect was seen for OTWI scores of all teeth combined. OTWI scores were not associated with occlusal guidance scheme. The occlusal condition of having fewer than 10 teeth in each arch appears to be a risk factor for increased occlusal tooth wear. Occlusal wear was more severe at the chewing side. Occlusal tooth wear was significantly associated with the nondental factors of age and sex.


tomm22 Knockdown-Mediated Hepatocyte Damages Elicit Both the Formation of Hybrid Hepatocytes and Biliary Conversion to Hepatocytes in Zebrafish Larvae.
The liver has a highly regenerative capacity. In the normal liver, hepatocytes proliferate to restore lost liver mass. However, when hepatocyte proliferation is impaired, biliary epithelial cells (BECs) activate and contribute to hepatocytes. We previously reported in zebrafish that upon severe hepatocyte ablation, BECs extensively contribute to regenerated hepatocytes. It was also speculated that BEC-driven liver regeneration might occur in another zebrafish liver injury model in which temporary knockdown of the mitochondrial import gene tomm22 by morpholino antisense oligonucleotides (MO) induces hepatocyte death. Given the importance of multiple BEC-driven liver regeneration models for better elucidating the mechanisms underlying innate liver regeneration in the diseased liver, we hypothesized that BECs would contribute to hepatocytes in tomm22 MO-injected larvae. In this MO-based liver injury model, by tracing the lineage of BECs, we found that BECs significantly contributed to hepatocytes. Moreover, we found that surviving, preexisting hepatocytes become BEC-hepatocyte hybrid cells in tomm22 MO-injected larvae. Intriguingly, both the inhibition of Wnt/β-catenin signaling and macrophage ablation suppressed the formation of the hybrid hepatocytes. This new liver injury model in which both hepatocytes and BECs contribute to regenerated hepatocytes will aid in better understanding the mechanisms of innate liver regeneration in the diseased liver.


Cytochrome P450 2C19 enzyme, Cytochrome P450 2C9 enzyme, and Cytochrome P450 2D6 enzyme allelic variants and its possible effect on drug metabolism: A retrospective study.
The objective of the present study was to assess the allelic variations of Cytochrome P450 (CYP) enzymes Cytochrome P450 2C19 (CYP2C19), Cytochrome P450 2C9 (CYP2C9), and Cytochrome P450 2D6 (CYP2D6) as they play a major role in drug metabolism. The interindividual genetic variabilities of these enzymes can account for different responsiveness as well as concentration fluctuations for a particular drug.During the period of 2017 to 2018 a total of 54 patients have received pharmacogenetic testing at the Department of Genetics and Molecular Medicine at Kaunas Clinics. According to the genotype-metabolic phenotypes of CYP2C19, CYP2D6, CYP2C9 enzymes patients were classified according to the guidelines by Clinical Pharmacogenetics Implementation Consortium (CPIC): normal metabolizers (NMs), intermediate metabolizers (IMs), rapid metabolizers (RMs), ultrarapid metabolizers (UMs), and poor metabolizers (PMs).CYP2C19 enzyme allelic distribution: 18 patients (33.33%) with ∗1/∗1 genotype were NMs; 14 patients (25.93%) with ∗1/∗2; ∗2/∗17 genotypes were classified as IMs; 15 patients (27.78%) possessed ∗1/∗17 genotype and were RMs; 4 patients (7.4%) had ∗17/∗17 genotype with increased enzyme activity compared with RMs, were classified as UMs; 3 patients (5.56%) had ∗2/∗2 genotype and were marked as PMs. CYP2D6 enzyme allelic distribution: 26 patients (48.148%) contained ∗1/∗1,∗2/∗2,∗1/∗2,∗1/∗41,∗2/∗41 genotypes with normal enzymatic function so were accounted as NMs; 21 patients (38.89%) with ∗1/∗5, ∗2/∗4, ∗10/∗41, ∗1/∗4, ∗1/∗3, ∗2/∗5, ∗2/∗4, ∗2/∗6 genotypes were accounted as IMs; 2 patients (3.7%) possessed ∗2XN genotype and were accounted as UMs and 5 patients (9.26%) possessed ∗4/∗5,∗4/∗10,∗4/∗9,∗4/∗41 genotypes and had non-functional enzymatic activity so were accounted as PMs; CYP2C9 enzyme allelic distribution: 44 patients (81.48%) with∗1/∗1 genotype were NMs; 10 patients (18.52%) with ∗1/∗2;∗1/∗3 genotypes were IMs.The results of our study indicate that deviations from the normal enzymatic activity is common amongst Lithuanian people and combinatory genotyping of CYP2D6, CYP2C9, and CYP2C19 has to be promoted as an advanced method because of most commonly prescribed medicines like analgesics, antihypertensive, antidepressants are metabolized by multiple pathways involving enzymes in the CYP450 family.


Microfluidics: applications for analytical purposes in chemistry and biochemistry.
In this review, we present recent advancements and novel developments in fluidic systems for applied analytical purposes in chemistry, biochemistry, and life science in general that employ and reflect the full benefits of microfluidics. A staggering rise in publications related to integrated, all-in-one microfluidic chips capable of separation, reaction, and detection have been observed, all of which realise the principal of micro total analysis systems or lab-on-a-chip. These integrated chips actively adopt the scaling law concepts, utilising the highly developed fabrication techniques. Their aim is to multi-functionalise and fully automate devices believed to assist the future advancements of point-of-care, clinical, and medical diagnostics.


Genital Rejuvenation: The Next Frontier in Medical and Cosmetic Dermatology.
Genital rejuvenation encompasses not only the nonsurgical interventions but also the surgical procedures that are utilized to improve the functional aspects and/or enhance the aesthetic presentation of the genitalia of women (vaginal rejuvenation) and men (scrotal rejuvenation). Vaginal rejuvenation was introduced into the medical literature in 2007; yet, within the last decade, physician and patient interest in this field has markedly increased. In contrast, the term scrotal rejuvenation was only coined in 2018. Rejuvenation of the genitalia may be considered for hair-associated (alopecia and hypertrichosis), morphology-associated (vulvovaginal atrophy, excess clitoral or labial tissue, scrotal wrinkling, and vaginal or scrotal laxity), and vascular-associated (angiokeratomas) changes of the vagina and scrotum. As women and men gain insight into the conditions that are amendable to genital rejuvenation, the demand for vaginal rejuvenation and scrotal rejuvenation will likely increase. Genital rejuvenation may become the next frontier in medical and cosmetic dermatology and dermatologists have the opportunity to provide rejuvenation of the vagina and scrotum for their patients.


Cardiomyoplasty: ventricular reconstruction after tumor resection.
Although cardiac transplantation has been performed for complete removal of ventricular tumors, complete surgical resection with ventricular reconstruction is desirable. Thus patients with benign tumors would probably be cured, and those with malignant tumors would have a better prognosis. In this study extensive and complete surgical resection of ventricular tumors is followed by anatomic and functional ventricular reconstruction with a dynamic cardiomyoplasty procedure. Seven patients (mean age, 32.7 years) underwent complete resection of ventricular tumors. Histologic types were distributed as follows: fibroma in 2 patients and sarcoma, lymphosarcoma, hemangioma, lipoma, and metastatic angiosarcoma, respectively, in the remaining 5 patients. Six of the patients were considered candidates for heart transplantation because of the extent of tumor invasion. Surgery consisted of 4 steps: (1) tumor resection; (2) coronary artery resection (when invaded by the tumor) and coronary artery bypass grafting; (3) valvular reconstruction (when possible) or replacement; and (4) ventricular wall reconstruction with a pericardial patch for closure of the ventricular defect (neoendocardium) covered by the electrostimulated latissimus dorsi muscle flap (neomyocardium). All patients survived surgical intervention, but 2 late postoperative deaths are reported. Among the surviving patients, early complications played a major role in their postoperative course and consisted of arrhythmias, atrioventricular block necessitating a dual-chamber pulse generator, respiratory insufficiency, and heart failure. Two patients were assisted postoperatively with an intra-aortic balloon pump. On postoperative follow-up (mean, 72.4 +/- 8.5 months), an improvement in the patients' functional status was observed. Patients moved from a mean New York Heart Association functional class of 2.8 to a mean functional class of 1.2. The excellent long-term evolution without recurrence, ventricular dysfunction, and/or thromboembolic complications implies that cardiomyoplasty could be recommended as an alternative to heart transplantation for the therapy of large ventricular tumors.


Diagnosing erectile dysfunction: instruments for endocrine diagnosis.
Endocrine factors represent an important and potentially treatable cause of sexual dysfunction. The availability of a correct endocrinological diagnosis allows correct identification of most cases of sexual dysfunction in which the endocrine apparatus is involved. Not only the most frequent causes of endocrine sexual dysfunction, such as hypogonadism and hyperprolactinaemia, but almost all extra-gonadal endocrinopathies (hyper-and hypothyroidism, hyper- and hypocortisolism, steroidal secreting tumours, etc.) may have importance to a greater or lesser extent in sexual function. It is, therefore, necessary that the diagnostic process for sexual dysfunctions of an endocrine nature be as integrated and wide as possible, especially as such pathologies are normally extremely responsive to medical or surgical therapy.


Identification of mutations in the myocilin (MYOC) gene in Taiwanese patients with juvenile-onset open-angle glaucoma.
To investigate mutations in the promoter and coding regions of the myocilin (MYOC) gene in Taiwanese patients suffering from juvenile-onset open-angle glaucoma (JOAG). MYOC was analyzed for mutations in 48 unrelated Taiwanese probands with JOAG and in 100 healthy control subjects. Genomic DNA was extracted from peripheral blood leukocytes and then subjected to PCR to amplify exons, flanking introns and promoter regions of the MYOC gene. The amplified products were screened for base mutations by autosequence. Data from the two groups were then compared using the chi(2) test. Finally, the levels of MYOC transcripts were predicted by a neural network prediction system to study whether the intron mutations have any effect on the level of mRNA expression. The analysis revealed four MYOC mutations and six polymorphisms. The prevalence of MYOC gene mutations in this study was 12.5% (6/48). The mutations included one nonsense mutation (Arg46Stop; 3/6), one missense mutation (Val56Ala; 1/6), one intron mutation (c.604+228A>T; 1/6) as well as one mutation in the 3'-untranslated region (c.1515+73G>C; 1/6). In addition, although c.604+228A>T is an intron mutation and does not alter the content of the amino acid residue, the neural network prediction system revealed that it can potentially create a novel accept splice site during transcription. This mutation might affect the protein structure and consequently the normal function of myocilin. Our results indicate that the c.136C>T (Arg46Stop), c.158T>C (Val56Ala), c.604+228A>T, and c.1515+73G>C mutations of MYOC may be associated with JOAG. In addition, we suggest that the c.136C>T (Arg46Stop) mutation of MYOC is a hot spot in Taiwanese patients with JOAG.


Acute exposure to waterborne copper inhibits both the excretion and uptake of ammonia in freshwater rainbow trout (Oncorhynchus mykiss).
In freshwater fish, exposure to sub-lethal concentrations of waterborne copper (Cu) results in inhibitions of ammonia excretion (Jamm) and Na(+) uptake (J(Na)in), yet the mechanisms by which these occur are not fully understood. In the present study, rainbow trout (Oncorhynchus mykiss) fry exposed to 50μg/l Cu for 24h displayed a sustained 40% decrease in Jamm and a transient 60% decrease in J(Na)in. Previously, these effects have been attributed to inhibitions of gill Na(+)/K(+)-ATPase and/or carbonic anhydrase (CA) activities by Cu. Trout fry did not display significant reductions in the branchial activities of these enzymes or H(+)-ATPase over 24h Cu exposure. Recently, Rhesus (Rh) glycoproteins, bi-directional NH3 gas channels, have been implicated in the mechanism of Cu toxicity. Juvenile trout were exposed to nominal 0, 50, and 200μg/l Cu for 3-6h under control conditions (ammonia-free water) followed by 6h exposure to high environmental ammonia (HEA; 1.5mmol/l NH4HCO3). HEA led to significant ammonia uptake in control fish (0μg/l Cu), and exposure to 50 and 200μg/l Cu resulted in significant reductions of ammonia uptake during HEA exposure. This is the first evidence that Cu inhibits both the excretion and uptake of ammonia, implicating bi-directional Rh glycoproteins as a target for Cu toxicity. We propose a model whereby Rh blockade by Cu causes the sustained inhibition of Jamm and transient inhibition of J(Na)in, with H(+)-ATPase potentially aiding in J(Na)in recovery. More work is needed to elucidate the role of Rh proteins in sub-lethal Cu toxicity.


Synthetic Toll-Like Receptor 4 (TLR4) and TLR7 Ligands Work Additively via MyD88 To Induce Protective Antiviral Immunity in Mice.
We previously demonstrated that the combination of synthetic small-molecule Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity that is protective against influenza viruses in homologous, heterologous, and heterosubtypic murine challenge models. Combining the TLR4 and TLR7 ligands balances Th1 and Th2-type immune responses for long-lived cellular and neutralizing humoral immunity against the viral hemagglutinin. Here, we demonstrate that the protective response induced in mice by this combined adjuvant is dependent upon TLR4 and TLR7 signaling via myeloid differentiation primary response gene 88 (MyD88), indicating that the adjuvants function in vivo via their known receptors, with negligible off-target effects, to induce protective immunity. The combined adjuvant acts via MyD88 in both bone marrow-derived and non-bone marrow-derived radioresistant cells to induce hemagglutinin-specific antibodies and protect mice against influenza virus challenge. The protective efficacy generated by immunization with this adjuvant and recombinant hemagglutinin antigen is transferable with serum from immunized mice to recipient mice in a homologous, but not a heterologous, H1N1 viral challenge model. Depletion of CD4+ cells after an established humoral response in immunized mice does not impair protection from a homologous challenge; however, it does significantly impair recovery from a heterologous challenge virus, highlighting an important role for vaccine-induced CD4+ cells in cross-protective vaccine efficacy. The combination of the two TLR agonists allows for significant dose reductions of each component to achieve a level of protection equivalent to that afforded by either single agent at its full dose.IMPORTANCE Development of novel adjuvants is needed to enhance immunogenicity to provide better protection from seasonal influenza virus infection and improve pandemic preparedness. We show here that several dose combinations of synthetic TLR4 and TLR7 ligands are potent adjuvants for recombinant influenza virus hemagglutinin antigen induction of humoral and cellular immunity against viral challenges. The components of the combined adjuvant work additively to enable both antigen and adjuvant dose sparing while retaining efficacy. Understanding an adjuvant's mechanism of action is a critical component for preclinical safety evaluation, and we demonstrate here that a combined TLR4 and TLR7 adjuvant signals via the appropriate receptors and the MyD88 adaptor protein. This novel adjuvant combination contributes to a more broadly protective vaccine while demonstrating an attractive safety profile.


Tranexamic Acid Use in Pediatric Craniotomies at a Large Tertiary Care Pediatric Hospital: A Five Year Retrospective Study.
Tranexamic acid (TXA), a synthetic antifibrinolytic drug, has proven efficacy and is recommended for major pediatric surgery to decrease perioperative blood loss. Accumulating evidence suggests that TXA reduces bleeding and transfusion in a variety of adult neurosurgical settings. However, there is a paucity of research regarding TXA indications for pediatric neurosurgery and thus, there are currently no recommendations for its use with this specific population. The objective of this study is to evaluate the existing practice of TXA administration for pediatric neurosurgery at a U.S. tertiary care pediatric hospital over a five-year period. The authors conclude that TXA administration is feasible and should be considered for pediatric neurosurgical cases where potential blood loss is a concern.


[Laparoscopic adrenal gland surgery].
Minimally invasive adrenalectomy is now an accepted alternative to conventional adrenalectomy. As in open surgery, several different endoscopic approaches to the adrenal glands have been described. In principle, one must distinguish between the laparoscopic and the retroperitoneoscopic access. All adrenal tumors--pheochromocytomas included--except adrenal carcinomas can be removed endoscopically. However, the use of these techniques is limited in patients with particularly large tumors. The results reported to date are convincing. Only limited data are available as yet to compare conventional and endoscopic adrenalectomy. Because adrenal diseases requiring surgery are rare, endoscopic adrenalectomy is an operation that, for the present, will be limited to centers with a particular interest in laparoscopic and endocrine surgery.


Pyrimidoindole derivative UM171 enhances derivation of hematopoietic progenitor cells from human pluripotent stem cells.
In the field of hematopoietic regeneration, deriving hematopoietic stem cells (HSCs) from pluripotent stem cells with engraftment potential is the central mission. Unstable hematopoietic differentiation protocol due to variation factors such as serums and feeder cells, remains a major technical issue impeding the screening of key factors for the derivation of HSCs. In combination with hematopoietic cytokines, UM171 has the capacity to facilitate the maintenance and expansion of human primary HSCs in vitro. Here, using a serum-free, feeder-free, and chemically defined induction protocol, we observed that UM171 enhanced hematopoietic derivation through the entire process of hematopoietic induction in vitro. UM171 facilitated generation of robust CD34+CD45+ derivatives that formed more and larger sized CFU-GM as well as larger sized CFU-Mix. In our protocol, the derived hematopoietic progenitors failed to engraft in NOG mice, indicating the absence of long-term HSC from these progenitors. In combination with other factors and protocols, UM171 might be broadly used for hematopoietic derivation from human pluripotent stem cells in vitro.


Monoclonal antibodies to the human insulin receptor that activate glucose transport but not insulin receptor kinase activity.
Three mouse monoclonal antibodies were produced that reacted with the alpha subunit of the human insulin receptor. All three both immunoprecipitated 125I-labeled insulin receptors from IM-9 lymphocytes and competitively inhibited 125I-labeled insulin binding to its receptor. Unlike insulin, the antibodies failed to stimulate receptor autophosphorylation in both intact IM-9 lymphocytes and purified human placental insulin receptors. Moreover, unlike insulin, the antibodies failed to stimulate receptor-mediated phosphorylation of exogenous substrates. However, like insulin, two of the three antibodies stimulated glucose transport in isolated human adipocytes. One antibody, on a molar basis, was as potent as insulin. These studies indicate, therefore, that monoclonal antibodies to the insulin receptor can mimic a major function of insulin without activating receptor kinase activity. They also raise the possibility that certain actions of insulin such as stimulation of glucose transport may not require the activation of receptor kinase activity.


Neonatal septicemia due to group B streptococci--perinatal risk factors and outcome of subsequent pregnancies.
All cases of early onset group B streptococcal (GBS) septicemia in infants born at Karolinska Hospital 1975-1986 were reviewed. GBS-septicemia was diagnosed in 40 infants within the first five days of life. The incidence was 1.24 per 1000 births. Fifty-five percent of the infants were preterm and 48% were born more than or equal to 12 hours after rupture of membranes. Prematurity and/or prolonged rupture of membranes were present in 83% of all neonates with fatal outcome. Case fatality was 22%. Deliveries by both cesarean section (31%) and vacuum extraction (26%) were increased in the mothers when compared to an overall incidence of 14 and 12% (p less than 0.01). Twenty-four (89%) of 27 mothers had low type specific IgG antibodies against the infecting GBS-serotype. Late onset GBS-septicemia was diagnosed in only two infants during the period. Seventeen mothers went through 24 subsequent pregnancies. In 11 of those the mothers were colonized with GBS and 10 received penicillin prophylaxis during pregnancy and/or delivery. None of the infants born after prophylaxis were colonized with GBS. Two were born prematurely and all had an uneventful course; whereas one infant delivered at 26 weeks gestation of a colonized untreated mother died of GBS-septicemia. Screening of parturients at risk and selective antibiotic prophylaxis may help to prevent early onset GBS-septicemia.


Factors associated with frailty in geriatric patients with and without sarcopenia in Vietnam.
This study aimed to investigate the relationship between sarcopenia and frailty and examine factors associated with frailty among older patients with and without sarcopenia. This cross-sectional study was conducted on older inpatients and outpatients in Vietnam. Participants aged 60 years or older were consecutively enrolled in the study. Sarcopenia was defined using the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Fried's frailty phenotype was applied to define frailty. Logistic regression models with frailty as the dependent variable were applied. A total of 835 patients (mean age: 71.3 years, SD 8.4) were recruited. The overall prevalence of frailty was 17%. Among participants with and without frailty, 92% and 47% had sarcopenia, respectively. In unadjusted analysis, sarcopenia was significantly associated with increased frailty (OR 12.3, 95% CI 6.7-22.6) and remained significant after adjustment for sociodemographic factors (OR 6.3, 95% CI: 3.0-12.6) and for both sociodemographic and clinical factors (OR 5.4, 95% CI: 2.4-12.2). Among participants with sarcopenia, older age, inpatient status, having a high risk for falls, malnutrition and a history of hospitalisation in the last year were significantly associated with frailty. Among participants without sarcopenia, the factors associated with frailty were older age, inpatient status, low educational level, high risk of falls and malnutrition. Our study results highlighted that sarcopenia and frailty are two related but distinct geriatric syndromes.


Focused ultrasound enhanced molecular imaging and gene therapy for multifusion reporter gene in glioma-bearing rat model.
The ability to monitor the responses of and inhibit the growth of brain tumors during gene therapy has been severely limited due to the blood-brain barrier (BBB). A previous study has demonstrated the feasibility of noninvasive in vivo imaging with 123I-2'-fluoro-2'-deoxy-5-iodo-1-β-D-arabinofuranosyluracil (123I-FIAU) for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) cancer gene expression in an experimental animal model. Here, we tested the enhancement of SPECT with 123I-FIAU and ganciclovir (GCV) treatment in brain tumors after BBB disruption induced by focused ultrasound (FUS) in the presence of microbubbles. We established an orthotopic F98 glioma-bearing rat model with trifusion reporter genes. The results of this study showed that the rat model of HSV1-tk-expressing glioma cells could be successfully detected by SPECT imaging after FUS-induced BBB disruption on day 10 after implantation. Compared to the control group, animals receiving the GCV with or without sonication exhibited a significant antitumor activity (P < 0.05) of glioma cells on day 16 after implantation. Moreover, combining sonication with GCV significantly inhibited tumor growth compared with GCV alone. This study demonstrated that FUS may be used to deliver a wide variety of theranostic agents to the brain for molecular imaging and gene therapy in brain diseases.


Circulating angiopoietin-like protein 2 levels are associated with decreased renal function in HIV+ subjects on cART: A potential marker of kidney disease.
Chronic kidney disease (CKD) is an important cause of morbidity and mortality in HIV-infected individuals, even in the antiretroviral therapy (ART) era. Inflammatory cytokines and adipokines have been suggested to play a role in the development of CKD. The aim of the present study was to examine the circulating levels of a novel proinflammatory cytokine, angiopoietin-like protein 2 (ANGPTL2), in a cohort of 72 HIV-positive subjects on ART. HIV-positive patients were on cART for at least one year. Urine and blood samples were collected. Various factors were analyzed including body mass index (BMI), smoking, and presence/treatment for comorbidities such as diabetes. The estimated glomerular filtration rate was calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Plasma samples obtained were stored and used to measure sCD14 and ANGPTL2 levels. Data were presented as mean (± standard deviation) or median (interquartile range) for continuous variables. Categorical variables were expressed as number (%). Variables were compared using Student's t-test, Mann-Whitney test, or χ2 test. The results showed an independent negative association between plasma ANGPTL2 and CKD-EPI values. Further prospective studies on larger cohorts are needed to evaluate the pathogenetic role of ANGPTL2 as well as its use as a diagnostic marker of renal dysfunction.


Short-Term Outcomes After Total Shoulder Arthroplasty in Octogenarians: A Matched Analysis.
Introduction Studies have shown that the use of total shoulder arthroplasty is increasing every year in the United Stated at a rate higher than that of total hip or total knee arthroplasty. As the population of the United States continues to age, it is becoming more important for surgeons to understand the true impact of age on outcomes and complications following procedures such a total shoulder arthroplasty. The purpose of this study was to determine if octogenarians have poorer outcomes after total shoulder arthroplasty compared to a younger, matched control group. Methods Data was obtained through the American College of Surgeons National Surgical Quality Improvement Program database (ACS NSQIP). Patients who had undergone total shoulder arthroplasty were identified by Current Procedural Terminology code (23472). Indication for arthroplasty was determined by ICD9/10 code (osteoarthritis, fracture, other). Each octogenarian was matched 1:1 to a non-octogenarian based on sex, BMI, ASA class, medical comorbidities, functional status, and surgical indication for arthroplasty by propensity scoring. A subgroup analysis was performed to compare outcomes between only those patients who underwent TSA for osteoarthritis.Outcomes of interest were assessed between the two groups for statistical significance using a chi-squared test or fisher exact test for expected values of less than 5. Statistical significance was set at p<0.05. Results After matching, octogenarians were found to be at higher risk of readmission (4.7% vs. 3.3%, p=0.046), non-home discharge (27.1% vs. 9.4%, p<0.001), and overall surgical (4.4% vs. 2.5%, p=0.006) and medical complications (3.7% vs. 2.4%, p=0.039). In the setting of TSA for osteoarthritis only, however, octogenarians were only at higher risk for non-home discharge (22.4% vs. 7.5%, p<0.001). Conclusions Octogenarians are at higher risk of some complications following total shoulder arthroplasty but fewer than has been previously reported, particularly in the setting of arthroplasty for the treatment of arthritis.


Vascular endothelial growth factor gene insertion/deletion polymorphism is associated with Vitamin D level in Turkish patients with coronavirus disease 2019.
Coronavirus disease 2019 emerges as a disease caused by severe acute respiratory syndrome coronavirus 2. It is a systemic disease associated with vascular inflammation and endothelial damage. In this study, we aimed to investigate whether vascular endothelial growth factor gene insertion/deletion polymorphism is associated with coronavirus disease 2019 in the Turkish population. The study included 179 participants (79 patients with coronavirus disease 2019 and 100 controls). DNA isolation was made from peripheral blood, and then the polymerase chain reaction analysis was performed. When we analyze vascular endothelial growth factor gene insertion/deletion polymorphism in the study group, we found that the DD genotype and D allele were found to be statistically significantly different when compared to coronavirus disease 2019 patients with high vitamin D value (p=0.005 for DD genotype and p=0.006 for D allele) in the control group. In this high-level control group, when we analyze II+ID genotype versus DD, a statistically significant difference was also detected (p=0.007). As a result of the study, we found that DD genotype and D allele were associated with vitamin D level in Turkish patients with coronavirus disease 2019.


Quantification analysis of lactate dehydrogenase and C-reactive protein in evaluation of the severity and prognosis of the acute pancreatitis.
To evaluate the value of C-reactive protein (CRP) and lactate dehydrogenase (LDH) in assessing the severity and prognosis of acute pancreatitis (AP). A retrospective analysis was performed with the clinical data of 115 AP patients who were delivered to this hospital between December 2012 and December 2017 for treatment, in which there were 76 patients with mild AP (MAP group) and 39 with moderately severe AP (MSAP) and severe AP (SAP) (non-MAP group). Within 24 h after admission, we detected the levels of CRP, LDH and amylase (AMY) in serum, and according to the sensitivity and specificity of CRP, LDH and AMY, as well as the SROC curve, we evaluated the diagnostic value of these indicators in assessing the severity of AP. In serum, the levels of CRP and LDH in the non-MAP group were significantly higher than those in the MAP group (P <0.05). And in predicting the development of AP, the sensitivity, specificity and accordance rate of CRP were 59.0%, 97.4% and 84.3%, with a cut-off value of 176.00 mg/L; for LDH, these indexes were 94.9%, 88.2% and 90.4%, with a cut-off value of 235.50 U/L. Thus, LDH, combined with the CRP can well predict the incidence rate of the MODS and mortality rate of AP. Finally, we conclude that within 24 h after admission, the levels of CRP and LDH in patients can serve as indicators for evaluating the severity and prognosis of AP.


Highly Efficient Photocatalyst Based on a CdS Quantum Dots/ZnO Nanosheets 0D/2D Heterojunction for Hydrogen Evolution from Water Splitting.
A novel CdS/ZnO heterojunction constructed of zero-dimensional (0D) CdS quantum dots (QDs) and two-dimensional (2D) ZnO nanosheets (NSs) was rationally designed for the first time. The 2D ZnO NSs were assembled into ZnO microflowers (MFs) via an ultrasonic-assisted hydrothermal procedure (100 °C, 12 h) in the presence of a NaOH solution (0.06 M), and CdS QDs were deposited on both sides of every ZnO NS in situ by using the successive ionic-layer absorption and reaction method. It was found that the ultrasonic treatment played an important role in the generation of ZnO NSs, while NaOH was responsible to the assembly of a flower-like structure. The obtained CdS/ZnO 0D/2D heterostructures exhibited remarkably enhanced photocatalytic activity for hydrogen evolution from water splitting in comparison with other CdS/ZnO heterostructures with different dimensional combinations such as 2D/2D, 0D/three-dimensional (3D), and 3D/0D. Among them, CdS/ZnO-12 (12 deposition cycles of CdS QDs) exhibited the highest hydrogen evolution rate of 22.12 mmol/g/h, which was 13 and 138 times higher than those of single CdS (1.68 mmol/g/h) and ZnO (0.16 mmol/g/h), respectively. The enhanced photocatalytic activity can be attributed to several positive factors, such as the formation of a Z-scheme photocatalytic system, the tiny size effect of 0D CdS QDs and 2D ZnO NSs, and the intimate contact between CdS QDs and ZnO NSs. The formation of a Z-scheme photocatalytic system remarkably promoted the separation and migration of photogenerated electron-hole pairs. The tiny size effect effectively decreased the recombination probability of electrons and holes. The intimate contact between the two semiconductors efficiently reduced the migration resistance of photogenerated carriers. Furthermore, CdS/ZnO-12 also presented excellent stability for photocatalytic hydrogen evolution without any decay within five cycles in 25 h.


Stability and compatibility of tegaserod from crushed tablets mixed in beverages and foods.
The stability and compatibility of tegaserod from crushed tablets in selected beverages and foods were studied. Suspensions of tegaserod maleate tablets containing 6 mg of the drug base were prepared by crushing the tablets and mixing the powder with tap water, apple juice, orange juice, milk, applesauce, yogurt, and chocolate-hazelnut spread. Drug stability, drug comparability, suspension homogeneity, and completeness of a dose were measured by high-performance liquid chromatography at intervals up to three days at 20-25 degrees C and 5 degrees C. In vitro dissolution profiles were determined for crushed tegaserod tablets in water, apple juice, orange juice, and applesauce. Tegaserod from crushed tablets was stable in and compatible with water, apple juice, orange juice, and applesauce, and the suspensions were homogeneous. The complete dose was delivered with these media. The dissolution profiles of crushed tegaserod tablets in water and in apple juice were comparable to those of intact tablets; the dissolution profiles in orange juice and applesauce were not comparable with those of intact tablets. The results with milk, yogurt, and chocolate-hazelnut spread as vehicles were inconclusive. The suspension in milk was not homogeneous, and the dose was incomplete. Tegaserod from crushed tablets was stable in and compatible with water, apple juice, orange juice, and applesauce, but the dissolution profile in orange juice or applesauce was not acceptable. Apple juice may be the preferred vehicle because it masks the drug's taste.


Cholecysto-hydatid cyst fistula.
We present a case of recurrent hydatid cyst liver in a 32-year-old female. Previous surgery was performed 8 years ago elsewhere. Pre-operative assessment at presentation revealed a 110 x 105 mm hydatid cyst in the right lobe of the liver. On exploration, a 5 mm fistulous communication was found between the hydatid cyst and the gallbladder. Patient was subjected to endocystectomy (partial cystectomy), cholecystectomy and closure of the fistula followed by obliteration of the cavity with omentum. Postoperative recovery was uneventful.


The septation apparatus, an autonomous system in budding yeast.
Actomyosin ring contraction and chitin primary septum deposition are interdependent processes in cell division of budding yeast. By fusing Myo1p, as representative of the contractile ring, and Chs2p for the primary septum, to different fluorescent proteins we show herein that the two processes proceed essentially at the same location and simultaneously. Chs2p differs from Myo1p in that it reflects the changes in shape of the plasma membrane to which it is attached and in that it is packed after its action into visible endocytic vesicles for its disposal. To ascertain whether this highly coordinated system could function independently of other cell cycle events, we reexamined the septum-like structures made by the septin mutant cdc3 at various sites on the cell cortex at the nonpermissive temperature. With the fluorescent fusion proteins mentioned above, we observed that in cdc3 at 37 degrees C both Myo1p and Chs2p colocalize at different spots of the cell cortex. A contraction of the Myo1p patch could also be detected, as well as that of a Chs2p patch, with subsequent appearance of vesicles. Furthermore, the septin Cdc12p, fused with yellow or cyan fluorescent protein, also colocalized with Myo1p and Chs2p at the aberrant locations. The formation of delocalized septa did not require nuclear division. We conclude that the septation apparatus, composed of septins, contractile ring, and the chitin synthase II system, can function at ectopic locations autonomously and independently of cell division, and that it can recruit the other elements necessary for the formation of secondary septa.


A new model for suprapubic catheterization: the MediPlus Seldinger suprapubic catheter.
Insertion of a suprapubic catheter is one of the essential skills that all surgeons should master. It provides an alternative way to drain the bladder in cases where urethral catheterization is contraindicated or deemed difficult. It also has a role in elective cases where long-term drainage of the bladder is required. In this article, we discuss the MediPlus suprapubic catheter kit, which offers a new and potentially promising technique for safe introduction of the catheter into the bladder.


A New Modality for Cancer Treatment--Nanoparticle Mediated Microwave Induced Photodynamic Therapy.
Photodynamic therapy (PDT) has attracted ever-growing attention as a promising modality for cancer treatment. However, due to poor tissue penetration by light, photodynamic therapy has rarely been used for deeply situated tumors. This problem can be solved if photosensitizers are activated by microwaves (MW) that are able to penetrate deeply into tissues. Here, for the first time, we report microwave-induced photodynamic therapy and exploit copper cysteamine nanoparticles as a new type of photosensitizer that can be activated by microwaves to produce singlet oxygen for cancer treatment. Both in vitro and in vivo studies on a rat osteosarcoma cell line (UMR 106-01) have shown significant cell destruction using copper cysteamine (Cu-Cy) under microwave activation. The heating effects and the release of copper ions from Cu-Cy upon MW stimulation are the main mechanisms for the generation of reactive oxygen species that are lethal bullets for cancer destruction. The copper cysteamine nanoparticle-based microwave-induced photodynamic therapy opens a new door for treating cancer and other diseases.


Developmental changes in sleep biology and potential effects on adolescent behavior and caffeine use.
Adolescent development includes changes in the biological regulatory processes for the timing of sleep. Circadian rhythm changes and changes to the sleep-pressure system (sleep homeostasis) during adolescence both favor later timing of sleep. These changes, combined with prevailing social pressures, are responsible for most teens sleeping too late and too little; those who sleep least report consuming more caffeine. Although direct research findings are scarce, the likelihood of use and abuse of caffeine-laden products grows across the adolescent years due, in part, to excessive sleepiness.


Can Machine Learning Methods Predict Extubation Outcome in Premature Infants as well as Clinicians?
Though treatment of the prematurely born infant breathing with assistance of a mechanical ventilator has much advanced in the past decades, predicting extubation outcome at a given point in time remains challenging. Numerous studies have been conducted to identify predictors for extubation outcome; however, the rate of infants failing extubation attempts has not declined. To develop a decision-support tool for the prediction of extubation outcome in premature infants using a set of machine learning algorithms. A dataset assembled from 486 premature infants on mechanical ventilation was used to develop predictive models using machine learning algorithms such as artificial neural networks (ANN), support vector machine (SVM), naïve Bayesian classifier (NBC), boosted decision trees (BDT), and multivariable logistic regression (MLR). Performance of all models was evaluated using area under the curve (AUC). For some of the models (ANN, MLR and NBC) results were satisfactory (AUC: 0.63-0.76); however, two algorithms (SVM and BDT) showed poor performance with AUCs of ~0.5. Clinician's predictions still outperform machine learning due to the complexity of the data and contextual information that may not be captured in clinical data used as input for the development of the machine learning algorithms. Inclusion of preprocessing steps in future studies may improve the performance of prediction models.


Transmission of MRSA between humans and animals on duck and turkey farms.
The objectives of this study were to estimate the prevalence of MRSA on duck and turkey farms, identify risk factors for human carriage and study transmission between animals and humans. On 10 duck and 10 turkey farms, samples were taken from animals, poultry houses, home residences and humans and cultured using pre-enrichment and selective enrichment. MRSA isolates were typed by spa typing and multiple-locus variable number tandem repeat analysis (MLVA) typing. A subset of isolates from animals and humans was investigated using whole-genome mapping. MRSA was found on one duck farm and three turkey farms. On duck farms, all humans were MRSA negative. On turkey farms, 5 of 11 farmers, 2 of 32 family members and 15 of 49 samples from the home residences were MRSA positive. Individuals with daily contact with turkeys were significantly more often MRSA positive than individuals without daily contact. All MRSA isolates belonged to livestock-associated MLVA complex 398, belonged to spa type t011, were negative for Panton-Valentine leucocidin, were mecC negative and were mecA positive. Whole-genome mapping proved a valuable tool to study the transmission of livestock-associated MRSA and showed that on two turkey farms the isolates from the animals and humans were indistinguishable or closely related, indicating transmission. MRSA carriage in individuals in daily contact with turkeys was significantly higher than that in individuals only living on the farms or than in the general Dutch population. Therefore, persons with a high degree of contact with turkeys have an increased risk of MRSA carriage, and we propose that they should be screened prior to hospitalization in order to decrease the risk of nosocomial transmission.


Route-asymmetrical optical transmission and logic gate based on optical gradient force.
We put forward a route-asymmetrical optical transmission scheme employing optical gradient force, which means that forward and backward propagation of an optical device have different transmittance provided they are not present simultaneously. The device is based on optical gradient force between two single-mode waveguides followed by a Mach-Zehnder interferometer. Our numerical investigation shows that the forward transmittance is about -6 dB while the backward transmittance is suppressed below -20.5 dB in C + L bands. The proposed device is passive, wideband, and compatible with complementary metal-oxide semiconductor (CMOS) process. Furthermore, we demonstrate the applications of route-asymmetrical transmission such as an all-optical switch and all-optical AND gate for all-optical information processing.


Hurdles to helium gas laparoscopy and a readily available alternative.
Although multiple series of helium insufflation-assisted laparoscopic surgery are reported, we encountered difficulty at many levels when arranging a laparoscopic nephrectomy with helium insufflation. We present our experience with attempting to use helium gas as an insufflant and our successful use of argon gas as an adjunct to CO(2) insufflation with a case report as illustration. The patient is a 66-year-old man with a progressively enlarging 3.1-cm right renal mass. His history is significant for severe chronic obstructive pulmonary disease, necessitating home oxygen and frequent cycles of steroids. In line with the patient's desire for a minimally invasive procedure, we scheduled a laparoscopic nephrectomy with helium gas. Helium tanks need specialized adapters (yoke) to connect to laparoscopic insufflators; once the yoke was located, we were informed that helium is not approved by the Food and Drug Administration for use as an insufflant and we could not proceed with its use without a full hospital institutional review board review. We elected to use low-pressure CO(2) insufflation augmented by argon gas insufflation via the argon beam coagulator. The patient tolerated the low-pressure CO(2) /argon gas pneumoperitoneum without difficulty. There were no significant changes in the hemodynamic variables throughout the procedure. This patient was extubated at the completion of the procedure, and there were no intraoperative or postoperative complications. Although numerous reports and case series exist regarding the use of helium as an alternate insufflation agent to CO(2), the logistics of obtaining the correct helium yoke and hospital approval are cumbersome for this rarely indicated agent. A far simpler alternative, with similar physiologic effects, is the use of argon gas as an adjunct to CO(2) insufflation, or in lieu of CO(2) insufflation.


Partial purification and chemical characterization of macrophage cytotoxicity factor (MCF, MAF) and its separation from migration inhibitory factor (MIF).
Macrophage cytotoxicity factor (MCF) was purified in 3 consecutive steps including adsorption chromatography on Matrex Gel Red A, hydrophobic chromatography on phenylalanine-Sepharose, and isoelectric focusing. MCF was characterized as a protein with a m.w. of approximately 30,000 by gel filtration on Sephadex G-100 with 2 isoelectric points at 7.4 and 8.4 in the presence of urea. The unpurified supernatant was fairly stable provided that manipulations favoring adsorption to membrane materials used for dialysis or ultrafiltration were omitted. The partially purified preparation was highly unstable. Trypsin treatment did not affect MCF activity, whereas chymotrypsin destroyed it. Treatment with glycosidases and neuraminidase or cultivation of cells in the presence of 2-deoxy-D-glucose or tunicamycin did not impair the MCF activity. MCF was separated from migration inhibitory factor (MIF) by 2 methods: first, isoelectric focusing in the presence of urea, and second by gel filtration on Ultrogel. MCF could be separated from interferon by chromatography on poly(I)-Sepharose.


Assessment of post-operative pain in children: who knows best?
Pain assessment in children can be extremely challenging. Most professional bodies recommend that parents or carers should be involved with their child's pain assessment; but the evidence that parents can accurately report pain on behalf of their children is mixed. Our objective was to examine whether there were differences in post-operative pain score ratings between the child, nurse and parent or carer after surgery. Cognitively intact children aged four upwards, undergoing all surgical procedures, whose parents were present in the post-anaesthetic recovery unit (PACU), were studied. Thirty-three children were included in the study. The numerical rating scale was used to rate the child's pain by the child, nurse and parent on arrival to the PACU and prior to discharge. We found strong correlations between children's, nurses' and parent's pain scores on admission and discharge from PACU. The intraclass correlation coefficient of pain scores reported by children, nurses and parents was 0.94 (95% confidence intervals 0.91-0.96, P<0.0001). In cognitively intact children, it is adequate to manage pain based upon the assessment of children's and nurses' pain scores alone. The numerical rating scale appeared to be suitable for younger children. Whilst there are benefits of parents being present in recovery, it is not essential for optimizing the assessment of pain.


Topographic mapping of quantitative EEG variables in chronic heavy marihuana users: empirical findings with psychiatric patients.
EEG studies of marihuana use dating back to 1945 were reviewed. The earlier studies depended upon visual analysis of the tracing, and while some minor frequency and amplitude variations occurred in some subjects, there was no consistent THC induced change noticeable across subjects. Quantitative EEG studies of acute exposure to THC came later and produced reliable findings of a placebo controlled dose dependent THC induced increase in relative power of alpha, combined with decreased alpha frequency and a reduction of beta activity. These findings were reported for data collected from central-occipital derivations only. In our present investigation, we report that chronic heavy THC users have EEGs characterized by (1) increased absolute power of all frequencies over all cortical areas (2) hyperfrontality of elevated relative and absolute power and coherence values of alpha activity, and (3) a decrease in relative power of all non-alpha frequencies. Methodological issues were discussed and some suggestions were made for continuing research in this area.


Focused directed evolution of β-glucosidases: theoretical versus real effectiveness of a minimal working setup and simple robust screening.
Here we present an optimized procedure to generate amino acid variations at specific site(s) of proteins, followed by a simple one-step screen for mutants with the desired β-glucosidase activity. The procedure was evaluated by introducing sequence variation into a codon specifying a non-functional variant of the catalytic nucleophile (E401) of the maize β-glucosidase Zm-p60.1. Observed and theoretically expected frequencies of the four possible variants of the codon and the two possible phenotypes (functional and non-functional) were investigated. Deviations in codon and phenotype frequencies were expressed as a coefficient. This coefficient was then used to estimate the extent of oversampling, of the mutant library, which would be necessary to compensate for the underrepresentation of some sequences. This evaluation of the overall performance of the method allows experimentally derived parameters to be incorporated into mutant library design. This method combines the application of a well-defined distribution of variability with a reliable screening process. Thus, it facilitates the production of novel functional variants of β-glucosidases for either fundamental studies or potential biotechnological applications.


Ultrasound biomicroscopy of corneal hydrops in Terrien's marginal degeneration.
Terrien's marginal degeneration (TMD) is a rare form of corneal ectasia. Few case reports have documented hydrops of the cornea in patients with TMD. We present the first case known to us of corneal hydrops in TMD where there is stromal edema in addition to the aqueous cystic cavities, and the first case demonstrating ultrastructural anatomy of this entity by ultrasound biomicroscopy.