[Idiopathic Frey's syndrome under the appearance of a recurrent otitis externa].
Frey syndrome has been observed especially in patients who have undergone a parotidectomy operation, but also in zoster herpes, in parotiditis, condilea fractures, obstetric traumatisms with forceps and in surgery of the meningioma of the cerebellopontine angle. It also appears without previous surgery, like in our case. In these circumstances it is believed that a clinical neuritis, primary or secondary to a neighbouring inflammation may cause the start of this disorder. Several treatments have been suggested which highlights the difficulty of them. The most effective one is the intradermic injection of botulinum toxin type A. Its use in Frey's syndrome was initiated by Drobik and Laskawi in 1995. Since then the references to its use are numerous. Nevertheless, it is a treatment which has been introduced very few times in our country.


Long-term management of the ventilator-dependent patient: levels of disability and resocialization.
Home care of ventilator-dependent people is increasing in use due to improved management of respiratory failure and the development of effective portable ventilators. Home care programmes depend on an interdisciplinary team of health care professionals working with the ventilator-dependent person and caregivers in the home (family member, friend, or attendant). The caregiver is responsible for personal care assistance, for equipment monitoring, and for tracheostomy care, if the ventilator-dependent person has one, including changing of the tracheostomy tube, cleaning of stomas, and suctioning. Polio survivors of the 1950's epidemics in the United States have lived at home with ventilatory support and are the paradigm for the new ventilator-dependent population.


Probabilistic numerics and uncertainty in computations.
We deliver a call to arms for probabilistic numerical methods: algorithms for numerical tasks, including linear algebra, integration, optimization and solving differential equations, that return uncertainties in their calculations. Such uncertainties, arising from the loss of precision induced by numerical calculation with limited time or hardware, are important for much contemporary science and industry. Within applications such as climate science and astrophysics, the need to make decisions on the basis of computations with large and complex data have led to a renewed focus on the management of numerical uncertainty. We describe how several seminal classic numerical methods can be interpreted naturally as probabilistic inference. We then show that the probabilistic view suggests new algorithms that can flexibly be adapted to suit application specifics, while delivering improved empirical performance. We provide concrete illustrations of the benefits of probabilistic numeric algorithms on real scientific problems from astrometry and astronomical imaging, while highlighting open problems with these new algorithms. Finally, we describe how probabilistic numerical methods provide a coherent framework for identifying the uncertainty in calculations performed with a combination of numerical algorithms (e.g. both numerical optimizers and differential equation solvers), potentially allowing the diagnosis (and control) of error sources in computations.


Isolation and characterization of a chitinase gene from entomopathogenic fungus Verticillium lecanii.
Entomopathogenic fungus Verticillium lecanii is a promising whitefly and aphid control agent. Chitinases secreted by this insect pathogen have considerable importance in the biological control of some insect pests. An endochitinase gene Vlchit1 from the fungus was cloned and overexpressed in Escherichia coli. The Vlchit1 gene not only contains an open reading frame (ORF) which encodes a protein of 423 amino acids (aa), but also is interrupted by three short introns. Vlchit1 protein showed that the chitinase Vlchit1 has a (a/b)8 TIM barrel structure. Overexpression test and Enzymatic activity assay indicated that the Vlchit1 is a functional enzyme that can hydrolyze the chitin substrate, so the Vlchit1 gene can service as a useful gene source for genetic manipulation leading to strain improvement of entomopathogenic fungi or constructing new transgenic plants with resistance to various fungal and insects pests.


Surgical ablation of atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials.
The aim of this review was to assess the effect of concomitant surgical atrial fibrillation (AF) ablation on postoperative freedom from AF and patient-important outcomes. We searched Cochrane CENTRAL, MEDLINE, and EMBASE databases from inception to May 2016 for randomized controlled trials (RCTs) evaluating surgical AF ablation using any lesion set vs. no surgical AF ablation in adults with AF undergoing cardiac surgery. We performed screening, risk-of-bias evaluation, and data collection independently and in duplicate. We evaluated risk of bias with the modified Cochrane tool, quality of evidence using GRADE framework, and pooled data with a random-effects model. Of the 23 included studies, only one was considered at low risk of bias. Surgical AF ablation was associated with more freedom from AF at 12 months [relative risk (RR) = 2.32, 95% confidence interval (CI) 1.92-2.80; P < 0.001, low quality]. However, no significant difference was seen in mortality (RR = 1.07, 95% CI 0.72-1.52; P = 0.41, moderate quality), stroke (RR = 1.19, 95% CI 0.59-2.39; P = 0.63, moderate quality), or pacemaker implantation (RR = 1.28, 95% CI 0.85-1.95; P = 0.24, high quality). Comparing biatrial and left-sided lesion sets showed no difference in mortality (P-interaction = 0.60) or stroke (P-interaction = 0.12). At 12 months, biatrial procedures led to more freedom from AF (RR = 2.80, 95% CI 2.13-3.68; P < 0.0001) when compared with left-sided ablation (RR = 2.00, 95% CI 1.68-2.39; P < 0.0001) (P-interaction = 0.04) Biatrial procedures appear to increase the risk for pacemaker (RR = 2.68, 95% CI 1.41-5.11; P = 0.002) compared with no ablation while left-sided ablation does not (RR = 1.08, 95% CI 0.67-1.74; P = 0.76) (P-interaction = 0.03). Surgical AF ablation during cardiac surgery improves freedom from AF. However, impact on patient-important outcomes including mortality and stroke has not shown statistical significance in current RCT evidence. Biatrial compared with left-sided lesion sets showed no difference in mortality or stroke but were associated with significantly increased freedom from AF and risk for pacemaker requirement.


ILCOR Scientific Knowledge Gaps and Clinical Research Priorities for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: A Consensus Statement.
Despite significant advances in the field of resuscitation science, important knowledge gaps persist. Current guidelines for resuscitation are based on the International Liaison Committee on Resuscitation 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations, which includes treatment recommendations supported by the available evidence. The writing group developed this consensus statement with the goal of focusing future research by addressing the knowledge gaps identified during and after the 2015 International Liaison Committee on Resuscitation evidence evaluation process. Key publications since the 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations are referenced, along with known ongoing clinical trials that are likely to affect future guidelines. © 2018 European Resuscitation Council and American Heart Association, Inc. Published by Elsevier B.V. All rights reserved.


Thioridazine reverses trastuzumab resistance in gastric cancer by inhibiting S-phase kinase associated protein 2-mediated aerobic glycolysis.
Trastuzumab constitutes the fundamental component of initial therapy for patients with advanced human epidermal growth factor receptor 2 (HER-2)-positive gastric cancer (GC). However, the efficacy of this treatment is hindered by substantial challenges associated with both primary and acquired drug resistance. While S-phase kinase associated protein 2 (Skp2) overexpression has been implicated in the malignant progression of GC, its role in regulating trastuzumab resistance in this context remains uncertain. Despite the numerous studies investigating Skp2 inhibitors among small molecule compounds and natural products, there has been a lack of successful commercialization of drugs specifically targeting Skp2. To discover a Skp2 blocker among currently available medications and develop a therapeutic strategy for HER2-positive GC patients who have experienced progression following trastuzumab-based treatment. Skp2 exogenous overexpression plasmids and small interfering RNA vectors were utilized to investigate the correlation between Skp2 expression and trastuzumab resistance in GC cells. Q-PCR, western blot, and immunohistochemical analyses were conducted to evaluate the regulatory effect of thioridazine on Skp2 expression. A cell counting kit-8 assay, flow cytometry, a amplex red glucose/glucose oxidase assay kit, and a lactate assay kit were utilized to measure the proliferation, apoptosis, and glycolytic activity of GC cells in vitro. A xenograft model established with human GC in nude mice was used to assess thioridazine's effectiveness in vivo. The expression of Skp2 exhibited a negative correlation with the sensitivity of HER2-positive GC cells to trastuzumab. Thioridazine demonstrated the ability to directly bind to Skp2, resulting in a reduction in Skp2 expression at both the transcriptional and translational levels. Moreover, thioridazine effectively inhibited cell proliferation, exhibited antiapoptotic properties, and decreased the glucose uptake rate and lactate production by suppressing Skp2/protein kinase B/mammalian target of rapamycin/glucose transporter type 1 signaling pathways. The combination of thioridazine with either trastuzumab or lapatinib exhibited a more pronounced anticancer effect in vivo, surpassing the efficacy of either monotherapy. Thioridazine demonstrates promising outcomes in preclinical GC models and offers a novel therapeutic approach for addressing trastuzumab resistance, particularly when used in conjunction with lapatinib. This compound has potential benefits for patients with Skp2-proficient tumors.


The accuracy and completeness for receipt of colorectal cancer care using Veterans Health Administration administrative data.
The National Comprehensive Cancer Network and the American Society of Clinical Oncology have established guidelines for the treatment and surveillance of colorectal cancer (CRC), respectively. Considering these guidelines, an accurate and efficient method is needed to measure receipt of care. The accuracy and completeness of Veterans Health Administration (VA) administrative data were assessed by comparing them with data manually abstracted during the Colorectal Cancer Care Collaborative (C4) quality improvement initiative for 618 patients with stage I-III CRC. The VA administrative data contained gender, marital, and birth information for all patients but race information was missing for 62.1% of patients. The percent agreement for demographic variables ranged from 98.1-100%. The kappa statistic for receipt of treatments ranged from 0.21 to 0.60 and there was a 96.9% agreement for the date of surgical resection. The percentage of post-diagnosis surveillance events in C4 also in VA administrative data were 76.0% for colonoscopy, 84.6% for physician visit, and 26.3% for carcinoembryonic antigen (CEA) test. VA administrative data are accurate and complete for non-race demographic variables, receipt of CRC treatment, colonoscopy, and physician visits; but alternative data sources may be necessary to capture patient race and receipt of CEA tests.


Facile Formation of High-Quality InGaN/GaN Quantum-Disks-in-Nanowires on Bulk-Metal Substrates for High-Power Light-Emitters.
High-quality nitride materials grown on scalable and low-cost metallic substrates are considerably attractive for high-power light-emitters. We demonstrate here, for the first time, the high-power red (705 nm) InGaN/GaN quantum-disks (Qdisks)-in-nanowire light-emitting diodes (LEDs) self-assembled directly on metal-substrates. The LEDs exhibited a low turn-on voltage of ∼2 V without efficiency droop up to injection current of 500 mA (1.6 kA/cm(2)) at ∼5 V. This is achieved through the direct growth and optimization of high-quality nanowires on titanium (Ti) coated bulk polycrystalline-molybdenum (Mo) substrates. We performed extensive studies on the growth mechanisms, obtained high-crystal-quality nanowires, and confirmed the epitaxial relationship between the cubic titanium nitride (TiN) transition layer and the hexagonal nanowires. The growth of nanowires on all-metal stack of TiN/Ti/Mo enables simultaneous implementation of n-metal contact, reflector, and heat sink, which greatly simplifies the fabrication process of high-power light-emitters. Our work ushers in a practical platform for high-power nanowires light-emitters, providing versatile solutions for multiple cross-disciplinary applications that are greatly enhanced by leveraging on the chemical stability of nitride materials, large specific surface of nanowires, chemical lift-off ready layer structures, and reusable Mo substrates.


The Effects of Repeated Reading on Reading Fluency for Students With Reading Disabilities.
The purpose of this research was to systematically review the effects of repeated reading (RR) interventions on reading fluency to provide instructional strategies for students with reading disabilities (RD). Correct words per minute were coded as an outcome variable in a search that yielded 34 RR intervention studies from 1990 to 2014 for students with RD in K-12. The estimated overall Hedges' g of the 39 independent effect sizes indicated the positive effects of RR on gains in reading fluency for students with RD, especially at the elementary grade level. The current findings also suggested that a combination of RR and a listening passage preview would be the most effective method for students with RD.


Survey of the contamination of foodstuffs of animal origin by Shiga toxin producing Escherichia coli serotype O157:H7 in Belgium from 1999 to 2003.
A survey of the prevalence of Shiga toxin-producing Escherichia coli (STEC) of O157 serotype in foodstuffs of animal origin (beef, veal, pork, chicken, fish) from 1999 to 2003 in Belgium was performed. STEC strains were only isolated from beef with a prevalence of 0.73%. This percentage is low in comparison with the prevalence in other countries. Among the 76 isolated STEC O157 strains, 75% belonged to the serotype O157:H7 and 25% to the serotype O157 non H7. Moreover, the most frequent pathotype was eae stx2 ehxA (74%).


12-O-Tetradecanoylphorbol-13-acetate stimulation of DNA synthesis in cultured preneoplastic familial polyposis colonic epithelial cells but not in normal colonic epithelial cells.
We have developed a method for the routine primary culture of human colonic epithelial cells. Cultured cells exhibited characteristic epithelial structures, including a brush border and junctional complexes. Flask-like goblet cells containing mucus were also seen within the epithelial monolayer. [3H]Thymidine labeling indices were used to distinguish between cultured cells from familial polyposis patients, other patients at high risk to develop colon cancer, and low-risk control subjects. 12-O-Tetradecanoylphorbol-13-acetate (TPA) at 10 ng/ml enhanced DNA synthesis an average of 8-fold when assayed by labeling index in colonic epithelial cells from five of six familial polyposis patients. No such stimulation by TPA was seen in cells from 13 high-risk patients without familial polyposis or in cells from five low-risk subjects. Hundreds of benign polyps can be found in the colons of familial polyposis patients. One such benign tubular adenoma exhibited the same enhancement of DNA synthesis by TPA as normal-appearing epithelial cells from a biopsy adjacent to that polyp. Mitogenic response to TPA had been seen earlier in cells from each of four tubular adenomas (Friedman, E. Cancer Res., 41: 4588-4599, 1981). Both familial polyposis epithelial cells and adenoma cells are considered preneoplastic, but they are not identical because their patterns of actin cytoskeletal organization differ. These results imply that familial polyposis epithelial cells are precursors of tubular adenoma cells, and their transition to the more advanced preneoplastic cells of this benign tumor is influenced by endogeneous tumor promoters.


Accuracy of the Surprise Question on an Inpatient Oncology Service: A Multidisciplinary Perspective.
The surprise question (SQ), "Would you be surprised if your patient died within a year?", has been studied in the cancer population as a prognostic prompt. Studies have almost exclusively directed the SQ to physicians, whereas perspectives of nurses remain underevaluated. We asked the SQ for patients admitted to an inpatient medical oncology service to medical oncology, palliative care, and hospital medicine teams and bedside nurses. We performed a 1-year retrospective chart review to identify how concordant various provider types were in their prognostic estimations and identified the missed opportunity rate (MOR) defined as the number of patients who died within a particular time frame but who the providers had predicted would be alive and may not have had a palliative approach. Oncologists had higher MORs for the 6-month and 1-year SQ when compared with hospital medicine providers. Bedside nurses were least concordant in their estimations of prognosis and had higher MORs for all time frames of the SQ. Missed opportunities might have significant implications for the end-of-life care for cancer patients, and continued research is needed to understand what influences provider prognostication and how this impacts palliative care utilization for patients with life-limiting disease.


Pathogenicity of Salmonella strains isolated from egg shells and the layer farm environment in australia.
In Australia, the egg industry is periodically implicated during outbreaks of Salmonella food poisoning. Salmonella enterica serovar Typhimurium and other nontyphoidal Salmonella spp., in particular, are a major concern for Australian public health. Several definitive types of Salmonella Typhimurium strains, but primarily Salmonella Typhimurium definitive type 9 (DT9), have been frequently reported during egg-related food poisoning outbreaks in Australia. The aim of the present study was to generate a pathogenicity profile of nontyphoidal Salmonella isolates obtained from Australian egg farms. To achieve this, we assessed the capacity of Salmonella isolates to cause gastrointestinal disease using both in vitro and in vivo model systems. Data from in vitro experiments demonstrated that the invasion capacity of Salmonella serovars cultured to stationary phase (liquid phase) in LB medium was between 90- and 300-fold higher than bacterial suspensions in normal saline (cultured in solid phase). During the in vivo infection trial, clinical signs of infection and mortality were observed only for mice infected with either 10(3) or 10(5) CFU of S. Typhimurium DT9. No mortality was observed for mice infected with Salmonella serovars with medium or low invasive capacity in Caco-2 cells. Pathogenicity gene profiles were also generated for all serovars included in this study. The majority of serovars tested were positive for selected virulence genes. No relationship between the presence or absence of virulence genes by PCR and either in vitro invasive capacity or in vivo pathogenicity was detected. Our data expand the knowledge of strain-to-strain variation in the pathogenicity of Australian egg industry-related Salmonella spp.


The role of the N-terminal amphipathic helix in bacterial YidC: Insights from functional studies, the crystal structure and molecular dynamics simulations.
The evolutionary conserved YidC is a unique dual-function membrane protein that adopts insertase and chaperone conformations. The N-terminal helix of Escherichia coli YidC functions as an uncleaved signal sequence and is important for membrane insertion and interaction with the Sec translocon. Here, we report the first crystal structure of Thermotoga maritima YidC (TmYidC) including the N-terminal amphipathic helix (N-AH) (PDB ID: 6Y86). Molecular dynamics simulations show that N-AH lies on the periplasmic side of the membrane bilayer forming an angle of about 15° with the membrane surface. Our functional studies suggest a role of N-AH for the species-specific interaction with the Sec translocon. The reconstitution data and the superimposition of TmYidC with known YidC structures suggest an active insertase conformation for YidC. Molecular dynamics (MD) simulations of TmYidC provide evidence that N-AH acts as a membrane recognition helix for the YidC insertase and highlight the flexibility of the C1 region underlining its ability to switch between insertase and chaperone conformations. A structure-based model is proposed to rationalize how YidC performs the insertase and chaperone functions by re-positioning of N-AH and the other structural elements.


Standardization of the Coomassie Blue method for cerebrospinal fluid proteins.
Coomassie Brilliant Blue G-250 can be used to quantitatively determine proteins in cerebrospinal fluid. When the dye combines with protein, the absorption maximum of the dye shifts. The dye-protein color forms almost instantaneously and is stable for at least 1 h. The procedure is also insensitive to changes in temperature in the range of 20--30 degrees C. The absorptivities of the dye complexes with human albumin or globulin differ, thus a pure albumin or pure globulin standard is unsuitable; a standard containing 70% albumin and 30% globulins is the most appropriate for this application. A bichromatic approach to standardization increases the range of linearity of a calibration curve. The method gives values that are about 9% higher than a sodium sulfate-sulfosalicylic turbidimetric procedure for cerbrospinal fluid proteins.


Amino acid control of autophagic sequestration and protein degradation in isolated rat hepatocytes.
Sequestration of the inert cytosolic marker [14C]sucrose by sedimentable organelles was measured in isolated rat hepatocytes made transiently permeable to sucrose by means of electropermeabilization. Lysosomal integrity, protein degradation, autophagic sequestration, and other cellular functions were not significantly impaired by the electric treatment. Hepatocytes sequestered sucrose at an initial rate of approximately 10%/h, which is threefold higher than the estimated rate of autophagic-lysosomal protein degradation. Almost one-third would appear to represent mitochondrial fluid uptake; the rest was nearly completely and specifically inhibited by 3-methyladenine (3MA) and can be regarded as autophagic sequestration. A complete amino acid mixture was somewhat less inhibitory than 3MA, and partially antagonized the effect of the latter. This paradoxical effect, taken together with the high sequestration rate, may suggest heterogeneity as well as selectivity in autophagic sequestration. There was no detectable recycling of sequestered [14C]sucrose between organelles and cytosol. Studies of individual amino acids revealed histidine as the most effective sequestration inhibitor. Leucine may have a regulatory function, as indicated by its unique additive/synergistic effect, and a combination of Leu + His was as effective as the complete amino acid mixture. Asparagine inhibited sequestration only 20%, i.e., its very strong effect on overall (long-lived) protein degradation must partially be due to post-sequestrational inhibition. The lysosomal (amine-sensitive) degradation of short-lived protein was incompletely inhibited by 3MA, indicating a contribution from nonautophagic processes like crinophagy and endocytic membrane influx. The ability of an amino acid mixture to specifically antagonize the inhibition of short-lived protein degradation by AsN + GIN (but not by 3MA) may suggest complex amino acid interactions at the level of fusion between lysosomes and other vesicles in addition to the equally complex interactions at the level of autophagic sequestration.


Drying temperature and relative humidity effects on wheat gluten film properties.
The mechanical and physical properties of glycerol-plasticized wheat gluten films dried at different temperatures (20, 50, and 80 degrees C) and relative humidities (35 and 70% RH) were investigated. Dispersion of wheat gluten was prepared at pH 11 in aqueous solution. Films were obtained by casting the wheat gluten suspension, followed by solvent evaporation in a temperature and relative humidity controlled chamber. Decreasing relative humidity altered most of the mechanical properties. At 35% RH, tensile strength increased when drying temperature increased. However, at 70% RH, tensile strength decreased when temperature increased. Thickness of the films decreased by increasing temperature. Hypothetical coating strength increased with increasing drying temperature at 35% RH. However, at 70% RH, a maximum value was observed at 50 degrees C. Films produced at 80 degrees C exhibited low solubility in aqueous solution. Addition of 1.5% (w/v) sodium dodecyl sulfate increased solubility of all of the films except the film dried at 50 degrees C and 70% RH. Overall, drying temperature and relative humidity affected mechanical and physical properties of the wheat gluten films. However, the effect of drying temperature was more pronounced than the effect of relative humidity.


Theory of rotational columnar structures of soft spheres.
There is a growing interest in cylindrical structures of hard and soft particles. A promising new method to assemble such structures has recently been introduced by Lee et al. [Lee, Gizynski, and Grzybowski, Adv. Mater. 29, 1704274 (2017)ADVMEW0935-964810.1002/adma.201704274]. They used rapid rotations around a central axis to drive spheres of lower density than the surrounding fluid towards the axis. This resulted in different structures as the number of spheres is varied. Here, we present comprehensive analytic energy calculations for such self-assembled structures, based on a generic soft sphere model, from which we obtain a phase diagram. It displays interesting features, including peritectoid points. These analytic calculations are complemented by preliminary numerical simulations for finite sample sizes with soft spheres. A similar analytic approach could be used to study packings of spheres inside cylinders of fixed dimensions, but with a variation in the number of spheres.


Interleukin-8 production by human mesothelial cells after direct stimulation with staphylococci.
Mesothelial cells (MC) are able to produce interleukin-8 (IL-8) after stimulation with IL-1 beta or tumor necrosis factor alpha. The aim of our study was to investigate whether MC are able to produce IL-8 after direct stimulation with clinically relevant bacteria. We observed a significant IL-8 response by the MC which were directly stimulated with viable staphylococci.


Fluorocarbon and dextran hemodilution in myocardial ischemia.
The effect of hemodilution, with a fluorocarbon erythrocyte substitute and with dextran, on myocardial ischemia induced by occlusion of the left anterior descending coronary artery was investigated in anesthetized dogs. The resulting changes were compared to those in a control group subjected to a sham-exchange procedure. The hematocrit was reduced to 23% to 26% by dilution with fluorocarbon and dextran, while it was maintained at 42% to 46% in the control group. At similar hematocrit levels, during ventilation with 100% oxygen, the fluorocarbon-diluted blood transported 4 ml/dl more oxygen in the plasma phase than the dextran-diluted blood. Left ventricular function was not significantly altered and there was a marked improvement of blood flow to the ischemic zone. The mass of dehydrogenase-stained ischemic myocardium (21% of left ventricular mass) was marginally (p less than 0.06) smaller in the dogs with fluorocarbon-diluted blood than in the control group (29% of left ventricular mass). The output of creatine phosphokinase by the heart was also reduced (p less than 0.05) by hemodilution with fluorocarbon. These findings suggest that hemodilution with an oxygen-transporting blood substitute may have marginal beneficial effects on the collateral perfusion of acutely ischemic myocardium following sudden coronary artery occlusion.


Genome increase as a clock for the origin and evolution of life.
The size of non-redundant functional genome can be an indicator of biological complexity of living organisms. Several positive feedback mechanisms including gene cooperation and duplication with subsequent specialization may result in the exponential growth of biological complexity in macro-evolution. I propose a hypothesis that biological complexity increased exponentially during evolution. Regression of the logarithm of functional non-redundant genome size versus time of origin in major groups of organisms showed a 7.8-fold increase per 1 billion years, and hence the increase of complexity can be viewed as a clock of macro-evolution. A strong version of the exponential hypothesis is that the rate of complexity increase in early (pre-prokaryotic) evolution of life was at most the same (or even slower) than observed in the evolution of prokaryotes and eukaryotes. The increase of functional non-redundant genome size in macro-evolution was consistent with the exponential hypothesis. If the strong exponential hypothesis is true, then the origin of life should be dated 10 billion years ago. Thus, the possibility of panspermia as a source of life on earth should be discussed on equal basis with alternative hypotheses of de-novo life origin. Panspermia may be proven if bacteria similar to terrestrial ones are found on other planets or satellites in the solar system. This article was reviewed by Eugene V. Koonin, Chris Adami and Arcady Mushegian.


Selective and sensitive monitoring of caspase-1 activity by a novel bioluminescent activity-based probe.
The role of caspase-1 in inflammation has been studied intensely over recent years. However, the research of caspase-1 has remained difficult mainly due to the lack of sensitive and selective tools to monitor not only its abundance but also its activity. Here we present a bioluminescent activity-based probe (ABP) for caspase-1, developed by the Reverse Design concept, where chemically optimized protease inhibitors are turned into selective substrate ABPs. The probe exhibits excellent selectivity for caspase-1 and ∼1000-fold increase in sensitivity compared to available fluorogenic peptidic caspase-1 substrates. Moreover, we have been able to monitor and quantify specific caspase-1 activity directly in cell lysates. The activity correlated well with processing of prointerleukin-1β and prointerleukin-18 in phorbol 12-myristate 13-acetate (PMA)-stimulated cells. A detectable caspase-1 activity was present also in nonstimulated cells, consistent with processing of constitutively expressed prointerleukin-18.


Effect of internal derangements and degenerative bone changes on the minimum thickness of the roof of the glenoid fossa in temporomandibular joint.
The aim of this study is to investigate the effect of internal derangements and degenerative bone changes on the minimum thickness of the roof of the glenoid fossa (RGF). MRI and cone beam CT records of temporomandibular joints (TMJ) of 68 patients were evaluated retrospectively in this study. The joints were divided into three groups according to TMJ disc status which had been diagnosed in MRI: normal disc status, anterior disc displacement with reduction, and anterior disc displacement without reduction. Cone beam CT was used to evaluate the degenerative bone changes of TMJ and to measure the minimum thickness of RGF. The joints were categorized as "with osteoarthritis (OA)" or "without OA". The findings of OA were determined as erosion, osteophyte, flattening, sclerosis, and pseudocyst. No significant relationship was found between gender and the thickness of RGF (p > 0.05). RGF was found significantly higher in "with OA" group compared to "without OA" group (p < 0.001). No significant difference was found between disc displacement groups for minimum thickness of RGF (p > 0.005). No significant difference was found between condyles without erosion and condyles with erosion for the minimum thickness of RGF (p = 0.272). In the present study, osteophyte, sclerosis, flattening, and pseudocyst were found to be associated with the minimum thickness of RGF. Osteophyte, flattening, pseudocyst, and sclerosis have an influence on RGF thickness. The minimum thickness of RGF is not significantly correlated with internal derangements. Erosion is not significantly correlated with RGF thickness. RGF thickness may be unaffected by the early stages of OA.


Novel inhibitory activity for serine protease inhibitor Kazal type-3 (Spink3) on human recombinant kallikreins.
Kallikrein-related peptidases (KLKs) are trypsin-like and chymotrypsin-like serine proteases which are expressed in several tissues. Their activity is tightly controlled by inhibitors including members of the serine protease Kazal-type (SPINK) family. These enzymes are promising targets for the treatment of skin desquamation, inflammation and cancer. Spink3 or caltrin I is expressed in mouse pancreas and males accessory glands and the resulting mature protein has been associated with different activities such as an inhibitor of trypsin and acrosin activity, calcium transport inhibitor in sperm and inhibitor of cell proliferation during embryogenesis. In this study, we produced a soluble recombinant Spink3 from mouse seminal vesicle (rmSpink3) that inhibited the activity of human KLKs. Using FRET substrates, rmSpink3 exhibited a potent inhibitory activity against human KLK2, KLK3, KLK5 (Ki ranging from 260 to 1500 nM), and to a lesser extent against KLK6, KLK1 and KLK7 (Ki around 3000 nM). As shown by mass spectrometry analysis of rmSpink3 incubated with trypsin, the inhibitor was not truncated by the target enzyme. Based on the in silico analysis of the expression of Spink3/SPINK1 and KLKs it is speculated that some KLKs may be natural targets of Spink3/SPINK1, however experimental confirmation using both proteins from mouse or human origin is needed. This work shows that rmSpink3 is a potent inhibitor of various human KLK members suggesting the potential of this molecule in the diagnosis/prevention of several human diseases.


Simultaneous bilateral spontaneous pneumothorax in an adult patient with cystic fibrosis.
Pneumothorax is a common complication in cystic fibrosis and is associated with worsening of lung function. However, bilateral simultaneous pneumothorax in cystic fibrosis is a rare condition. We describe the case of a 17-year-old female with cystic fibrosis who presented with spontaneous pneumothorax. Clinically, she presented right-sided chest pain and progressive breathlessness. The pneumothorax failed to resolve after the initial treatment (chest drainage). However, the patient was later successfully treated with additional chest drainage and talc pleurodesis. We also discuss the etiology and management of pneumothorax in patients with cystic fibrosis, since pneumothorax is associated with increased morbidity and mortality among such patients.


Use-Dependent Plasticity in Human Primary Motor Hand Area: Synergistic Interplay Between Training and Immobilization.
Training and immobilization are powerful drivers of use-dependent plasticity in human primary motor hand area (M1HAND). In young right-handed volunteers, corticomotor representations of the left first dorsal interosseus and abductor digiti minimi muscles were mapped with neuronavigated transcranial magnetic stimulation (TMS) to elucidate how finger-specific training and immobilization interact within M1HAND. A first group of volunteers trained to track a moving target on a smartphone with the left index or little finger for one week. Linear sulcus shape-informed TMS mapping revealed that the tracking skill acquired with the trained finger was transferred to the nontrained finger of the same hand. The cortical representations of the trained and nontrained finger muscle converged in proportion with skill transfer. In a second group, the index or little finger were immobilized for one week. Immobilization alone attenuated the corticomotor representation and pre-existing tracking skill of the immobilized finger. In a third group, the detrimental effects of finger immobilization were blocked by concurrent training of the nonimmobilized finger. Conversely, immobilization of the nontrained fingers accelerated learning in the adjacent trained finger during the first 2 days of training. Together, the results provide novel insight into use-dependent cortical plasticity, revealing synergistic rather than competitive interaction patterns within M1HAND.


Relationships of desire for no more children and socioeconomic and demographic factors in Sri Lankan women.
Data from the 1982 Sri Lanka Contraceptive Prevalence Survey are used to identify women who wish to stop childbearing; they differ in socioeconomic status from their counterparts who want more children. Educated women are more likely to be motivated to cease childbearing than non-educated women; Christian or Sinhalese/Buddhist women are more willing to stop childbearing than Moor/Muslim or Tamil/Hindu women. The relationships between sex composition of existing children and women's fertility desires indicate that although moderate son preference exists it does not affect their contraceptive behaviour. Among those who want no more children, 15% are at risk of unwanted pregnancy because they do not practise contraception. Again better education and being Christian or Sinhalese/Buddhist reduced the risk of unwanted pregnancy. Women whose husbands disapproved of contraception had over four times higher risk of unwanted pregnancy than women whose husbands approved.


Establishment and characterization of a new human eosinophilic leukemia cell line.
A human eosinophilic leukemia cell line, designated as EoL, was established from the peripheral blood of a patient with Philadelphia chromosome-negative eosinophilic leukemia (EL). The EoL cell line grows in single cell suspension with a doubling time of 48 hours for about one year. The reactivity of these cells was tested with a panel of monoclonal antibodies; they were found to express surface IA antigen, myeloid antigen (IF10, MY9) and membrane receptors for interleukin 2 (IL-2, Tac antigen). Under standard culture conditions, a small percentage of cells having more typical eosinophilic characteristics was present. These cells had cytoplasmic granules and were positive for Luxol-fast-blue and eosinophil peroxidase. Under culture conditions to induce the maturation of myeloid cells, such as alkaline medium or addition of dimethyl sulfoxide (DMSO), the frequency of cells with typical eosinophilic features increased to about 40%. In addition, cytogenetic studies showed that cultured cells and original leukemic blasts presented similar chromosome abnormalities. EoL seems to be a unique leukemic line committed to the eosinophilic lineage and can provide a useful in vitro model for the study of malignant eosinophilic properties.


Antioxidants to prevent respiratory decline in people with Duchenne muscular dystrophy and progressive respiratory decline.
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis, pneumonia, or the need for ventilatory support. There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weakness in general, and respiratory decline in particular. OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers to 23 March 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies. We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria. We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo. DATA COLLECTION AND ANALYSIS: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC and hospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function, forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF). MAIN RESULTS: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenone on respiratory function compared to placebo. The trial that contributed numerical data included patients with a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion, with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'. Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97; 64 participants; low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49; 63 participants; moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome, idebenone may result in less of a decline from baseline in FEV1 (MD 8.28%, 95% CI 0.89 to 15.67; 53 participants) and PEF (MD 6.27%, 95% CI 0.61 to 11.93; 1 trial, 64 participants) compared to placebo. Idebenone was associated with fewer serious adverse events (RR 0.42, 95% CI 0.09 to 2.04; 66 participants; low-certainty evidence) and little to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13; 66 participants; low-certainty evidence) compared to placebo. Idebenone may result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexors and MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors; both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection. The second trial, involving 255 participants, for which data were available only as a press release without numerical data, was prematurely discontinued due to futility after an interim efficacy analysis based on FVC. There were no safety concerns. The certainty of the evidence was low for most outcomes due to imprecision and publication bias (the lack of a full report of the larger trial, which was prematurely terminated). Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenone may result in slightly less of a decline in FVC and less of a decline in FEV1 and PEF, but probably has little to no measurable effect on change in quality of life. Idebenone is associated with fewer serious adverse events than placebo. Idebenone may result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data. Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.


Adult hemoglobins are synthesized in murine fetal hepatic erythropoietic cells.
The hemoglobins present in murine fetal hepatic erythroblasts on days 12-15 of gestation were studied by biochemical and immunocytologic techniques. In addition, fetal hepatic hemopoietic progenitor cells obtained from normal and mutant f/f mouse fetuses on days 11-13 of gestation were cultured in vitro with added erythropoietin and adult spleen cell conditioned medium to form large erythroid colonies. In all instances, adult hemoglobin synthesis was detected in the fetal hepatic erythroblasts and in the erythroid cell cultures in vitro. The tumor promoter, 12-O-tetradecanoylphorbol 13-acetate, enhanced the fetal hepatic erythroid colony growth in vitro, but did not alter the hemoglobin phenotypic expression.


Clinical and Aetiological Spectrum of Hypokalemic Flaccid Paralysis in Western Odisha.
To study the clinical profile of hypokalemic flaccid paralysis (HKFP) and to evaluate its causes. Fifty cases of hypokalemic flaccid paralysis (HKFP) admitted between November 2012 to October 2014 were taken up in the study. Serum potassium level < 3.5 mmol/ltr has been taken as hypokalemia. All cases were studied for spot and/or 24 hour urinary sodium / potassium, serum potassium / calcium / magnesium. Hypokalemic periodic paralysis (HPP) were diagnosed if there was spot/24 hour urine potassium excretion < 20mmol/ltr in presence of hypokalemia and flaccid weakness without other causes. EMG and nerve conduction study were done to exclude polyneuropathy and myopathic cases. Out of 50 cases of HKFP, male gender predominated (88%). Maximum number of cases (70%) occurred in 21 to 40 years of age. It occurred in all seasons but more in summer (58%). The precipitating factors were present in 76% of cases out of which high carbohydrate meal (28%), vomiting (16%), excessive sweating (8%), diarrhea (8%) and increased urination (12%) were present. Twenty percent of cases had recurrence (2 to 3 episodes most often) and 6% of cases had family history. Quadriparesis was seen in (54%), paraparesis (36%), hemiparesis (10%) and neck muscle weakness (32%). No case was present with respiratory paralysis or cranial nerve palsy. Twenty-one cases (42%) have very low potassium < 2.5 mmol/ltr, 11 cases (22%) with potassium level between 2.5 to 2.9 mmol/ltr and 18 cases (36%) with 3 to 3.5 mmol/ltr. There was no correlation between severity weakness and potassium level. Eleven cases (22%) had thyrotoxicosis and 3 cases (6%) were hypothyroid. Thirteen cases (26%) have excess urinary loss of potassium (≥20 mmol/ltr) of which 5 cases (10%) were distal renal tubular acidosis (dRTA), four cases (8%) were Gitelman's syndrome (GS) and in 4 cases exact cause could not be diagnosed. Non-renal / prior renal loss of potassium like diarrhea and excessive sweating was responsible in 8% cases each and vomiting in 10% of cases. One unique case of hypernatraemic hypokalemic paralysis (HHP) was found. Only 9 (18%) cases are hypokalemic periodic paralysis (HPP). HKFP is a hetergenous group of disease of which a significant number of patients had thyroid disorders mostly in the form of thyrotoxicosis followed by renal tubular dysfunctions like dRTA and GS; non-renal and prior renal loss of potassium like diarrhea, excessive sweating and vomiting respectively. Early recognition and prompt management of these conditions will give gratifying result and prevent further attacks in some cases.


ylm Has More than a (Z Anchor) Ring to It!
The division and cell wall (dcw) cluster is a highly conserved region of the bacterial genome consisting of genes that encode several cell division and cell wall synthesis factors, including the central division protein FtsZ. The region immediately downstream of ftsZ encodes the ylm genes and is conserved across diverse lineages of Gram-positive bacteria and Cyanobacteria In some organisms, this region remains part of the dcw cluster, but in others, it appears as an independent operon. A well-studied protein coded from this region is the positive FtsZ regulator SepF (YlmF), which anchors FtsZ to the membrane. Recent developments have shed light on the importance of SepF in a range of species. Additionally, new studies are highlighting the importance of the other conserved genes in this neighborhood. In this minireview, we aim to bring together the current research linking the ylm region to cell division and highlight further questions surrounding these conserved genes.


To prescribe or not to prescribe? Guidelines for spectacle prescribing in infants and children.
This paper discusses the considerations for prescribing a refractive correction in infants and children up to and including school age, with reference to the current literature. The focus is on children who do not have other disorders, for example, binocular vision anomalies, such as strabismus, significant heterophoria or convergence excess. However, refractive amblyogenic factors are discussed, as is prescribing for refractive amblyopia. Based on this discussion, guidelines are proposed, which indicate when to prescribe spectacles and what amount of refractive error should be corrected. It may be argued that these are premature because there are many questions that remain unanswered and we do not have the quality of evidence that we would like; the clinician, however, must make decisions on whether and what to prescribe when examining a child. These guidelines are to aid clinicians in their current clinical decision making.


Anti-androgen effects of the aromatase inhibitor, atamestane.
Prostatic hyperplasia can be induced in both intact and castrated dogs and in intact cynomolgus monkeys by the administration of androgenic steroids. Estrogenic steroids potentiate this effect in dogs. These changes also can be induced by androstenedione, which increases androgen and estrogen levels. Atamestane (ATA; 1-methyl-3,17-dione-androsta-1,4-diene), a potent aromatase inhibitor, inhibits some of the androstendione-induced effects; however, the nonsteroidal aromatase inhibitor, CGS-16949A, has been reported to decrease serum estradiol levels in adult rats but to have no effect on androgen-dependent organ weights. To examine the mechanisms by which ATA affects the rat prostate, in vivo and in vitro studies were conducted using adult rat ventral prostate (VP). Intact Sprague-Dawley rats were injected daily for 14 days with sesame seed oil, ATA (70 mg/kg/day), finasteride (FIN; 5 mg/kg/day), a 5 alpha-reductase inhibitor, or the combination of FIN plus ATA. A fifth group was castrated (CASTR) on day 1. The mean +/- standard error VP weight of the controls was 350 +/- 19 mg. It was reduced 17% (P < 0.05) by ATA, 29% (P < 0.001) by FIN, 48% (P < 0.001) by FIN plus ATA, and 86% (P < 0.001) by CASTR. The DNA/VP was reduced 22% (not significant) by ATA, 18% by FIN (not significant), 35% (P < 0.01) by FIN plus ATA, and 60% (P < 0.001) by CASTR. More significant changes were observed in RNA and protein. The mRNA for prostatein C3 was reduced by each of the treatments, but only CASTR increased the mRNA for TRPM-2, a marker of apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Low real-world early stent thrombosis rates in ST-elevation myocardial infarction patients and the use of bivalirudin, heparin alone or glycoprotein IIb/IIIa inhibitor treatment: A nationwide Swedish registry report.
In recent studies of primary percutaneous coronary intervention (PCI), bivalirudin compared with heparin has been associated with increased risk of stent thrombosis (ST). Our aim was to describe incidence and outcome of definite, early ST in a large contemporary primary PCI population divided in antithrombotic therapy subgroups. A prospective, observational cohort study of all 31,258 ST-elevation myocardial infarction patients who received a stent in Sweden from January 2007 to July 2014 in the SWEDEHEART registry was conducted. Patients were divided into 3 groups: bivalirudin, heparin alone, or glycoprotein IIb/IIIa inhibitor treated. Primary outcome measure was incidence of definite early ST (within 30 days of PCI). Secondary outcomes included all-cause mortality. Incidence of early ST was low, regardless of bivalirudin, heparin alone, or glycoprotein IIb/IIIa inhibitor treatment (0.84%, 0.94%, and 0.83%, respectively). All-cause mortality at 1 year was 20.7% for all ST patients (n = 265), compared with 9.1% in those without ST (n = 31,286; P < .001). Patients with ST days 2-30 had numerically higher all-cause mortality at 1 year compared with patients with ST days 0-1 (23% vs 16%, P = .20). In this real-world observational study of 31,258 ST-elevation myocardial infarction patients, the incidence of early ST was low, regardless of antithrombotic treatment strategy. Early ST was associated with increased mortality. Numerically higher all-cause mortality at 1 year was noted with ST days 2-30 compared with ST days 0-1 post-PCI.


Esophageal cancer: challenges, concerns, and recommendations for management amidst the COVID-19 pandemic.
Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, raising great concern, particularly in immunosuppressed cancer patients. The pandemic situation remains extremely dynamic, which necessitates proactive management decisions from oncologists and oncologic surgeons in effort to mitigate the risk of both SARS-CoV-2 infection and cancer metastasis. Esophageal cancer, in particular, is one of the deadliest types of malignancy worldwide, reflecting both aggressive biology and a lack of adequate treatment. Several challenges and concerns regarding the management of esophageal cancer have been raised in light of the ongoing viral pandemic. The primary aim of this review is to summarize the salient evidence for recommendations and optimal treatment strategies for patients with esophageal cancer amidst the COVID-19 pandemic.


Minimally invasive parathyroidectomy using cervical block: reasons for conversion to general anesthesia.
We investigated the frequency and reasons for conversion from cervical block anesthesia to general anesthesia (GA) in patients undergoing minimally invasive parathyroidectomy for primary hyperparathyroidism. Prospective case series. Tertiary university hospital. A total of 441 consecutive patients with primary hyperparathyroidism undergoing minimally invasive parathyroidectomy under cervical block and monitored anesthesia care using midazolam and narcotics were included. Patients with known multiglandular, familial, or secondary hyperparathyroidism or noninformative preoperative localization or those electing minimally invasive parathyroidectomy under GA were excluded. All patients underwent cervical block anesthesia and focused exploration using minimally invasive techniques. Intraoperative need for conversion from cervical block anesthesia to general endotracheal anesthesia. Of the 441 patients, 47 (10.6%) required conversion to GA. In all instances, conversion was performed in a controlled fashion using neuromuscular blockade, endotracheal intubation, and maintenance of the original surgical field preparation. Sixteen procedures were converted to accomplish simultaneous thyroid resections. An additional 15 were converted because the intraoperative parathyroid hormone level failed to decrease by at least 50% from the baseline after resection of the incident parathyroid tumor and extensive exploration was required. Eight procedures were converted because of technical difficulties related to ensuring adequate protection of the recurrent laryngeal nerve. Five procedures were converted to optimize patient comfort, and 2 were converted because of the intraoperative recognition of parathyroid carcinoma. One patient experienced a toxic reaction to lidocaine, causing a seizure. The vast majority of minimally invasive parathyroidectomies can be performed using cervical block anesthesia. However, conversion to GA is appropriate when unexpected intraoperative findings are encountered or for patient comfort.


Feasibility of Umbilical Hernia Repair Under Local Anesthesia and Monitored Anesthesia Care at a Veteran Affairs Hospital.
Local anesthesia (LA) for open umbilical hernia tissue repair (OUHTR) is not widely utilized in academic centers in the United States. We hypothesize that LA for OUHTR is feasible in a veteran patient population. From 2015 to 2019, 449 umbilical hernias were repaired at our institution utilizing a standardized technique in veteran patients. OUHTR was included in this analysis (n = 283). Since 2017, 18.7% (n = 53) UH were repaired under LA. We compared outcomes and operative times between general anesthesia and LA in patients undergoing OUHTR. Univariable and multivariable analyses were performed to determine significance. The entire cohort was composed of older (56.3 ± 12.1 years), White (75.5%), obese (body mass index [BMI] = 32.3 ± 4.6 kg/m2) men (98.0%). The average hernia size for the entire cohort was 2.42 ± 1.2 cm. The groups were similar in age and BMI. Patients with higher American Society of Anesthesiologists (ASA) (Odds ratio [OR] 3.1; 95% CI 1.5-6.8) and cardiovascular disease (OR 2.7; 95% CI 1.0-7.2) were more likely to receive LA. Recurrence (0.0% vs 6.0%; P = .9) and 30-day complications (6.0% vs 13%; P = .9) were similar between LA and GA after correcting for hernia size. Operating room times were reduced in the LA group (17.7 minutes; P < .05). None of the patients with LA required postanesthesia care unit for recovery. The patients who received LA reported being comfortable (78.9% of patients), with the worst reported pain being 2.4 ± 2.4 (out of a scale of 10), and 94.7% would elect to receive LA if they had another hernia repair. Patients who received LA had more cardiac disease and a higher ASA. Complications were similar between both groups. LA reduced operating room times. Patients were satisfied with LA.


LEDGF gene silencing impairs the tumorigenicity of prostate cancer DU145 cells by abating the expression of Hsp27 and activation of the Akt/ERK signaling pathway.
Lens epithelium-derived growth factor (LEDGF) maintains survival pathways by augmenting the transcription of stress-response genes such as small heat-shock protein 27. Recently, aberrant expression of LEDGF was found in prostate cancer (PC). Herein, we showed that LEDGF overexpression upregulated Hsp27 in PC cells, DU145, PC-3 and LNCaP and promoted antiapoptotic pathways in PCs. We found that these cells had higher abundance of Hsp27, which was correlated with the levels of LEDGF expression. Transactivation assay in DU145 cells revealed that transactivation of Hsp27 was related to the magnitude of LEDGF expression. Silencing of LEDGF in DU145 cells abrogated Hsp27 expression and inhibited stimulated cell proliferation, invasiveness and migration. These cells were arrested in S and G2 phase, and failed to accumulate cyclin B1, and showed increased apoptosis. Furthermore, LEDGF-depleted DU145 cells displayed elevated Bax and cleaved caspase 9 expression and reduced levels of Bcl2, Bcl-(XL). The activated survival pathway(s), ERK1/2 and Akt, were selectively decreased in these cells, which characteristically have lower tumorigenicity. Conversely, the depleted cells, when re-overexpressed with LEDGF or Hsp27, regained tumorigenic properties. Collectively, results reveal the involvement of LEDGF-mediated elevated expression of Hsp27-dependent survival pathway(s) in PC. Our findings suggest new lines of investigation aimed at developing therapies by targeting LEDGF or its aberrant expression-associated stimulated antiapoptotic pathway(s).


Mutational analysis of the envelope gene of Moloney murine leukemia virus.
The env gene products of Moloney murine leukemia virus are required for binding and entry of the virus into the target cell. Thirty-three linker insertion mutations were constructed throughout the env gene of Moloney murine leukemia virus. Twenty of the mutations were located in the surface protein (SU), and the remaining thirteen were located in the transmembrane protein (TM). The viability of the viruses containing these env gene mutations was determined by performing transient transfections and screening for the release of reverse transcriptase. Eleven viable mutants were isolated, nine in SU and two in TM. Three of the viable mutants were temperature sensitive. Four of the viable mutants were clustered in the carboxy terminus of SU. The env gene products of transfected cell lines which produced viable virus were analyzed. Our results indicated two regions of SU important for the stability of the SU/TM heteropolymer and one region important for the interaction of the env gene products with the viral core.


Angiotensin II up-regulates soluble epoxide hydrolase in vascular endothelium in vitro and in vivo.
Epoxyeicosatrienoic acids (EETs), as metabolites of arachidonic acid, may function as antihypertensive and antiatherosclerotic mediators for vasculature. EETs are degraded by soluble epoxide hydrolase (sEH). Pharmacological inhibition and genetic ablation of sEH have been shown to increase the level of EETs, and treating angiotensin II (Ang II)-infused hypertension rats with sEH-selective inhibitors increased the levels of EETs, with attendant decrease in systolic blood pressure. To elucidate the mechanisms by which Ang II regulates sEH expression, we treated human umbilical vein endothelial cells (ECs) and bovine aortic ECs with Ang II and found increased sEH expression at both the mRNA and protein levels. Transient transfection assays showed that the activity of the human sEH promoter was increased in ECs in response to Ang II. Further analysis of the promoter region of the sEH gene demonstrated that treatment with Ang II, like overexpression of c-Jun/c-Fos, activates the sEH promoter through an AP-1-binding motif. The binding of c-Jun to the AP-1 site of the sEH promoter was confirmed by chromatin immunoprecipitation assays. In contrast, adenovirus overexpression of the dominant-negative mutant of c-Jun significantly attenuated the effects of Ang II on sEH induction. An elevated level of sEH was found in the aortic intima of both spontaneously hypertensive rats and Ang II-infused Wistar rats. Blocking Ang II binding to Ang II receptor 1 by losartan abolished the sEH induction. Thus, AP-1 activation is involved in the transcriptional up-regulation of sEH by Ang II in ECs, which may contribute to Ang II-induced hypertension.


Interleukine-6 in critically ill COVID-19 patients: A retrospective analysis.
Coronavirus disease 2019 (COVID-19) appeared in China in December 2019 and has spread around the world. High Interleukin-6 (IL-6) levels in COVID-19 patients suggest that a cytokine storm may play a major role in the pathophysiology and are considered as a relevant parameter in predicting most severe course of disease. The aim of this study was to assess repeated IL-6 levels in critically ill COVID-19 patients admitted to our Intensive Care Unit (ICU) and to evaluate their relationship with patient's severity and outcome. We conducted a retrospective study on patients admitted to the ICU with a diagnosis of COVID-19 between March 10 (i.e. the date of the first admitted patients) and April 30, 2020. Demographic, clinical and laboratory data were collected at admission. On the day of IL-6 blood concentration measurement, we also collected results of D-Dimers, C-Reactive Protein, white blood cells and lymphocytes count, lactate dehydrogenase (LDH) and ferritin as well as microbiological samples, whenever present. Of a total of 65 patients with COVID-19 admitted to our ICU we included 41 patients with repeated measure of IL-6. There was a significant difference in IL-6 levels between survivors and non-survivors over time (p = 0.001); moreover, non survivors had a significantly higher IL-6 maximal value when compared to survivors (720 [349-2116] vs. 336 [195-646] pg/mL, p = 0.01). The IL-6 maximal value had a significant predictive value of ICU mortality (AUROC 0.73 [95% CI 0.57-0.89]; p = 0.01). Repeated measurements of IL-6 can help clinicians in identifying critically ill COVID-19 patients with the highest risk of poor prognosis.


Biventricular Noncompaction Cardiomyopathy Accompanied by Severe Pulmonary Valvular Stenosis and Patent Foramen Ovale.
Myocardial non-compaction (NC) is a rare genetic cardiomyopathy commonly believed to develop an intrauterine arrest of endomyocardial morphogenesis. NC is characterized by markedly hypertrabeculations in left ventricle or both ventricles with deep intertrabecular recesses. NC is usually seen isolated, but sometimes other congenital heart abnormalities may accompany to the myocardial NC. In this article we have presented an adult patient with biventricular myocardial NC cardiomyopathy accompanied by severe valvular pulmonary stenosis and patent foramen ovale.


Analysis of Curative Effect and Prognostic Factors of Radiotherapy for Esophageal Cancer Based on the CNN.
An esophageal cancer intelligent diagnosis system is developed to improve the recognition rate of esophageal cancer image diagnosis and the efficiency of physicians, as well as to improve the level of esophageal cancer image diagnosis in primary care institutions. In this paper, by collecting medical images related to esophageal cancer over the years, we establish an intelligent diagnosis system based on the convolutional neural network for esophageal cancer images through the steps of data annotation, image preprocessing, data enhancement, and deep learning to assist doctors in intelligent diagnosis. The convolutional neural network-based esophageal cancer image intelligent diagnosis system has been successfully applied in hospitals and widely praised by frontline doctors. This system is beneficial for primary care physicians to improve the overall accuracy of esophageal cancer diagnosis and reduce the risk of death of esophageal cancer patients. We also analyze that the efficacy of radiation therapy for esophageal cancer can be influenced by many factors, and clinical attention should be paid to grasp the relevant factors in order to improve the final treatment effect and prognosis of patients.


Advances in Oromandibular Reconstruction with Three-Dimensional Printing.
The mandibular structures are a complex anatomical structure that is fundamental to many physiological and homeostatic functions. It may be involved in many pathological processes that require partial or complete removal. When this happens, reconstruction is mandatory to improve cosmetic outcome with its effect on social interaction as well as to provide an opportunity for complete dental rehabilitation with restoration of all physiological functions. This article will review the different reconstructive options available for complex defects of the mandibular complex. It will highlight the surgical options available to maximize functional restoration. Finally, it will discuss computer modeling to optimize reconstructive planning.


Cognitive impairments in survivors of out-of-hospital cardiac arrest: a systematic review.
To describe the current evidence on the frequency and nature of cognitive impairments in survivors of out-of-hospital cardiac arrest. Systematic review. Pubmed, Embase, PsychInfo and Cinahl (1980-2006). No language restriction was imposed. The following inclusion criteria were used: participants had to be survivors of out-of-hospital cardiac arrest, 18 years or older, and there had to be least one cognitive outcome measure with a follow-up of 3 months or more. Case reports and qualitative studies were excluded. The articles were screened on title, abstract and full text by two reviewers. All selected articles were reviewed and assessed by two reviewers independently using a quality criteria list. Out of the 286 articles initially identified, 28 were selected for final evaluation. There was a high heterogeneity between the studies with regard to study design, number of participants, outcome measures and duration of follow-up. In general, the quality of the articles appeared low, with a few positive exceptions. The reported frequency of cognitive impairments in survivors of out-of-hospital cardiac arrest ranged from 6% to 100%. Memory problems were the most common cognitive impairment, followed by impairments in attention and executive functioning. Three high-quality prospective studies found that cognitive problems occurred in about half of the survivors of out-of-hospital cardiac arrest. There are few good studies on the frequency of cognitive impairments after out-of-hospital cardiac arrest. However, cognitive problems, in particular memory problems, seem common in survivors of out-of-hospital cardiac arrest.


Obstructive Sleep Apnea and Pathological Characteristics of Resected Pancreatic Ductal Adenocarcinoma.
Prospective studies have identified obstructive sleep apnea (OSA) as a risk factor for increased overall cancer incidence and mortality. The potential role of OSA in the risk or progression of specific cancers is not well known. We hypothesized that pathological differences in pancreatic cancers from OSA cases compared to non-OSA cases would implicate OSA in pancreatic cancer progression. We reviewed the medical records of 1031 patients who underwent surgical resection without neoadjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) at Johns Hopkins Hospital between 2003 and 2014 and compared the TNM classification of their cancer and their overall survival by patient OSA status. OSA cases were significantly more likely than non-OSA cases to have lymph node-negative tumors (37.7% vs. 21.8%, p = 0.004). Differences in the prevalence of nodal involvement of OSA vs. non-OSA cases were not associated with differences in other pathological characteristics such as tumor size, tumor location, resection margin status, vascular or perineural invasion, or other comorbidities more common to OSA cases (BMI, smoking, diabetes). A logistic regression model found that a diagnosis of OSA was an independent predictor of lymph node status (hazard ratio, 0.051, p = 0.038). Patients with OSA had similar overall survival compared to those without OSA (HR, 0.89, (0.65-1.24), p = 0.41). The observed pathological differences between OSA-associated and non-OSA-associated pancreatic cancers supports the hypothesis that OSA can influence the pathologic features of pancreatic ductal adenocarcinoma.


Graphene quantum dots obstruct the membrane axis of Alzheimer's amyloid beta.
Alzheimer's disease (AD) is a primary form of dementia with debilitating consequences, but no effective cure is available. While the pathophysiology of AD remains multifactorial, the aggregation of amyloid beta (Aβ) mediated by the cell membrane is known to be the cause for the neurodegeneration associated with AD. Here we examined the effects of graphene quantum dots (GQDs) on the obstruction of the membrane axis of Aβ in its three representative forms of monomers (Aβ-m), oligomers (Aβ-o), and amyloid fibrils (Aβ-f). Specifically, we determined the membrane fluidity of neuroblastoma SH-SY5Y cells perturbed by the Aβ species, especially by the most toxic Aβ-o, and demonstrated their recovery by GQDs using confocal fluorescence microscopy. Our computational data through discrete molecular dynamics simulations further revealed energetically favorable association of the Aβ species with the GQDs in overcoming peptide-peptide aggregation. Overall, this study positively implicated GQDs as an effective agent in breaking down the membrane axis of Aβ, thereby circumventing adverse downstream events and offering a potential therapeutic solution for AD.


Cross-infection of tumor cells by contact with T lymphocytes loaded with Newcastle disease virus.
Oncolytic virotherapy, a new type of cancer therapy involving viruses with oncolytic and immunostimulatory potential, is based on tumor selective viral replication, resulting in a specific lysis of tumor cells. Effective tumor targeting of oncolytic viruses remains a major problem because only a fraction of systemically applied viruses can reach the tumor tissue. We describe for the first time in an in vitro co-culture system that T lymphocytes can be loaded with Newcastle disease virus (NDV) in such a way that the virus load will be transferred to the tumor target cells upon contact of the T cells with tumor cells. The effectiveness of this NDV 'hitchhiking' on T cells can be influenced by the amount of virus, the ratio of T cells to tumor cells, the activation status of the T cells and by the virulence of the virus as shown by flow cytometry, quantitative real-time PCR and fluorescence microscopy. In a tumor neutralization assay in vitro, monolayers of human tumor cells could be completely and effectively destroyed by the addition of polyclonally activated human T cells loaded with oncolytic NDV. This process involves the formation of large T cell clusters as revealed by phase-contrast microscopy. Loading of oncolytic NDV onto activated T cells and adoptive transfer into a tumor-bearing host might enhance the efficacy of adoptive T cell therapy of tumors as well as tumor targeting of oncolytic viruses.


Characterisation of a phantom for multiwavelength quantitative photoacoustic imaging.
Quantitative photoacoustic imaging (qPAI) has the potential to provide high- resolution in vivo images of chromophore concentration, which may be indicative of tissue function and pathology. Many strategies have been proposed recently for extracting quantitative information, but many have not been experimentally verified. Experimental phantom-based validation studies can be used to test the robustness and accuracy of such algorithms in order to ensure reliable in vivo application is possible. The phantoms used in such studies must have well-characterised optical and acoustic properties similar to tissue, and be versatile and stable. Polyvinyl chloride plastisol (PVCP) has been suggested as a phantom for quality control and system evaluation. By characterising its multiwavelength optical properties, broadband acoustic properties and thermoelastic behaviour, this paper examines its potential as a phantom for qPAI studies too. PVCP's acoustic properties were assessed for various formulations, as well as its intrinsic optical absorption, and scattering with added TiO2, over a range of wavelengths from 400-2000 nm. To change the absorption coefficient, pigment-based chromophores that are stable during the phantom fabrication process, were used. These yielded unique spectra analogous to tissue chromophores and linear with concentration. At the high peak powers typically used in photoacoustic imaging, nonlinear optical absorption was observed. The Grüneisen parameter was measured to be [Formula: see text] = 1.01 ± 0.05, larger than typically found in tissue, though useful for increased PA signal. Single and multiwavelength 3D PA imaging of various fabricated PVCP phantoms were demonstrated.


Evaluation of the addition of adrenaline in a bilateral maxillary nerve block to reduce hemorrhage in dogs undergoing sharp staphylectomy for brachycephalic obstructive airway syndrome. A prospective, randomized study.
To assess the use of adrenaline (0.00198%) in a bilateral maxillary nerve block to reduce intraoperative hemorrhage in dogs undergoing staphylectomy for the treatment of brachycephalic obstructive airway syndrome (BOAS). Prospective, randomized, double-blinded controlled study. A total of 32 client owned, clinically affected dogs undergoing a cut and sew sharp staphylectomy for treatment of BOAS. A total of 16 dogs randomly assigned to adrenaline (A) group and 16 to no-adrenaline (NA) group. A bilateral maxillary nerve block was performed in all dogs prior to staphylectomy using lidocaine alone (group NA) or a combination of lidocaine and adrenaline (group A). Total hemorrhage was measured by weighing cotton-tipped applicators and swabs used on precision scales. In addition, a semi-quantitative hemorrhage score (1-5) was determined. Dogs were monitored for intraoperative hemodynamic stability during the procedure. Total hemorrhage was significantly (p = .013) lower in group A compared with group NA. The median semi-quantitative hemorrhage score was significantly lower for group A (p = .029) compared with group NA. No significant adverse effects were noted due to adrenaline usage. This study demonstrated that the use of adrenaline in a bilateral maxillary nerve block results in significantly lower intraoperative hemorrhage during cut and sew sharp staphylectomy and appeared safe to use. Potential clinical advantages include improved visualization, prevention of unnecessary blood loss and reduction in risk of blood aspiration.


H-ras induces glucose uptake in brown adipocytes in an insulin- and phosphatidylinositol 3-kinase-independent manner.
Fetal brown adipocytes (parental cells) expressed mainly Glut4 mRNA glucose transporter, the expression of Glut1 mRNA being much lower. At physiological doses, insulin stimulation for 15 min increased 3-fold glucose uptake and doubled the amount of Glut4 protein located at the plasma membrane. Moreover, phosphatidylinositol (PI) 3-kinase activity was induced by the presence of insulin in those cells, glucose uptake being precluded by PI 3-kinase inhibitors such as wortmannin or LY294002. H-raslys12-transformed brown adipocytes showed a 10-fold higher expression of Glut1 mRNA and protein than parental cells, Glut4 gene expression being completely down-regulated. Glucose uptake increased by 10-fold in transformed cells compared to parental cells; this uptake was unaltered in the presence of insulin and/or wortmannin. Transient transfection of parental cells with a dominant form of active Ras increased basal glucose uptake by 5-fold, no further effects being observed in the presence of insulin. However, PI 3-kinase activity (immunoprecipitated with anti-alphap85 subunit of PI 3-kinase) remained unaltered in H-ras permanent and transient transfectants. Our results indicate that activated Ras induces brown adipocyte glucose transport in an insulin-independent manner, this induction not involving PI 3-kinase activation.


Historical overview of the use of polynucleotides in cancer.
A search for effective inducers of interferon lead to the discovery of polyinosinic-polycytidylic acid [poly(I,C)], which was effective in rodents but not primates. Stabilization of poly(I,C) with poly-L-lysine and carboxymethyl-cellulose produced a derivative that is much more effective as an inducer in humans, but also more toxic. The ability of modified poly(I,C) to induce interferon in primates appears to be at least partly related to its ability to resist hydrolysis by nucleases. As the ability to induce interferon in primates increases, so does the toxicity. Several investigations have emphasized increasing the ease of hydrolysis in order to minimize toxicity. The inducers should not be considered just as a readily available source of interferon, as there are a number of differences between the biologic effects of the inducers and exogenous interferon.


Bis(cyclopentadienyl)titanium complexes of naphthalene-1,8-dithiolates, biphenyl 2,2'-dithiolates, and related ligands.
Titanocene 1,8-dithiolato-naphthalene and titanocene 2,2'-dithiolato biphenyl are produced by the reaction of naphtho[1,8-cd]-1,2-dithiole [or the biphenyl] with titanocene dicarbonyl (Ti(II)) in toluene at room temperature. The pro-ligands 2,7-di(tert-butyl)naphtho[1,8-cd]-1,2-dithiole, 5,6-dihydroacenaphtho[5,6-cd]-1,2-dithiole, 4,5-dithioacephenanthrylene, and 13,14-dithiapicene have been used in similar reactions with titanocene dicarbonyl to investigate the effect of steric bulk and of varying the naphthalene backbone on the final complex. The resulting Cp(2)TiS(2)Ar complexes (Ar = naphthalene) have been shown by temperature-dependent (1)H NMR spectroscopy to exist in solution in an envelope conformation with the six-membered TiS(2)C(3) rings undergoing inversion on the NMR time scale while the similar Cp(2)TiS(2)Ar complexes (Ar = biphenyl, binaphthalene) interconvert more rapidly. Titanocene 2,2'-disulfinato biphenyl has been synthesized by the salt elimination reaction of titanocene dichloride (Ti(IV)) and the disodium salt of biphenyl 2,2'-disulfinic acid. Finally, the effect of using pro-ligands where the sulfur atoms have been mono- or di-oxidized has been studied, and an interesting oxygen elimination reaction is observed for the S=O fragments but not for the SO(2) groups. All complexes have been characterized spectroscopically and seven X-ray structures are reported.


[Fluorosilicone oil heavier than water: a new aid in vitreoretinal surgery].
The specific gravity of fluorosilicone oil (trifluoropropylmethyl siloxane) is greater than that of water, and because of this it opens up new possibilities in vitreoretinal surgery: In cases of PVR detachment, retinal defects at the inferior margin or the posterior pole can be reliably tamponaded. If there is a peripheral retinal hole, the retina is reattached solely by injection of the oil - drainage is unnecessary, since the subretinal fluid is forced back into the vitreous cavity through the retinal defect. Retinal folds resulting from a giant tear will flatten out of their own accord. The present paper communicates initial clinical experience with fluorosilicone oil in 21 eyes (trauma and PVR detachment cases, some of which were considered hopeless). Even though the cases selected for surgery were extreme, reattachment was accomplished intraoperatively in all but one of them. Redetachment occurred in 4 out of 10 eyes following removal of the oil; this was rectified with low-density silicone oil. An immediate side-effect of the new oil was a transient iritis, seen in 5 out of 21 cases. A suspected side-effect after longer-term observation (mean 19 weeks) was that the oil promoted PVR. Out of 4 histologically studied membranes which proliferated under the oil, phagocytosis and foreign body reaction to the oil were found in one of the specimens. No retinal damage due to the oil could be detected by electroretinography. As an intraoperative aid, fluorosilicone oil is thoroughly to be recommended. If a long-term tamponade is essential, the fluorosilicone oil should be replaced with low-density silicone oil (dimethylsiloxane) after a few weeks.


[Effect of various aminoalkylenephosphonic compounds on the accumulation of radioactive beryllium in rats].
In experiments on rats it was shown that 10 aminoalkylenephosphonic compounds accelerate the excretion of beryllium -7 from a rat body. After the combined application of ethylene diamine-N-N'- bisisopropylidenephosphonic and diethylene triaminepentamethylenephosphonic acids, under similar irradiation conditions, an additive effect was obtained.


Goblet Cells Contribute to Ocular Surface Immune Tolerance-Implications for Dry Eye Disease.
Conjunctival goblet cell (GC) loss in dry eye is associated with ocular surface inflammation. This study investigated if conjunctival GCs contribute to ocular surface immune tolerance. Antigens applied to the ocular surface, imaged by confocal microscopy, passed into the conjunctival stroma through goblet cell associated passages (GAPs) in wild type C57BL/6 (WT), while ovalbumin (OVA) was retained in the epithelium of SAM pointed domain containing ETS transcription factor (Spdef) knockout mice (Spdef-/-) that lack GCs and are a novel model of dry eye. Stimulated GC degranulation increased antigen binding to GC mucins. Induction of tolerance to topically applied OVA measured by cutaneous delayed type hypersensitivity (DTH) was observed in WT, but not Spdef-/-. OTII CD4⁺ T cells primed by dendritic cells (DCs) from the conjunctival draining lymph nodes of Spdef-/- had greater IFN-γ production and lower Foxp3 positivity than those primed by WT DCs. These findings indicate that conjunctival GCs contribute to ocular surface immune tolerance by modulating antigen distribution and antigen specific immune response. GC loss may contribute to the abrogation of ocular surface immune tolerance that is observed in dry eye.


Assessment of the effects of access count in percutaneous nephrolithotomy on renal functions by technetium-99m-dimercaptosuccinic Acid scintigraphy.
Objective. To determine the effects of percutaneous nephrolithotomy on renal functions by using DMSA scintigraphy while considering access counts. Material and Methods. A total of 37 patients who had undergone percutaneous nephrolithotomy were included. Preoperative DMSA scans were performed a day before the surgery, whereas postoperative scans were randomized by evaluating them before (n = 25) and after (n = 12) the 6th postoperative month. Twenty-six of 37 cases underwent percutaneous nephrolithotomy with a single access site and 11 with multiple access sites. Results. There were no significant changes of total renal functions in the whole study group (P = 0.054). In the single access group, total functions were significantly elevated (P = 0.03) In the multiple access group, while treated site functions were significantly decreased (P = 0.01), total functions did not change significantly (P = 0.42). There was an insignificant decrease in those evaluated before the 6th postoperative month (P = 0.27) and an insignificant increase in the others (P = 0.11). Conclusion. We could not find a superiority of single access over multiple accesses. There is a temporary functional loss in the treated site.


Functional tests to quantify recovery following carpal tunnel release.
An objective test is needed to evaluate outcome following carpal tunnel release. A method to evaluate sensory and motor function related to carpal tunnel syndrome was investigated. Thirty-six candidates for carpal tunnel surgical procedures underwent a physical examination and nerve-conduction studies and completed a survey regarding symptoms. A battery of psychomotor and sensory tests was administered bilaterally immediately before surgery and again six weeks after surgery. The outcome variables included dynamic sensory gap-detection thresholds and rapid pinch-and-release rates. The average gap-detection threshold for the index finger in the surgical-treatment group demonstrated a 43% improvement, decreasing from 0.14 mm preoperatively to 0.08 mm at six weeks postoperatively (p < 0.01). The average gap-detection threshold for the index finger in the non-surgical-treatment group demonstrated no significant improvement, decreasing from 0.10 mm preoperatively to 0.08 mm postoperatively (p = 0.10). With the upper force level set at 10% of the maximum voluntary contraction, the average pinch rate in the surgical-treatment group demonstrated a 20% improvement, increasing from 6.65 pinches per second preoperatively to 7.96 pinches per second postoperatively (p < 0.001). The average pinch rate in the non-surgical-treatment group demonstrated a 7% improvement, increasing from 6.89 pinches per second preoperatively to 7.37 pinches per second at six weeks postoperatively (p < 0.05). Measurable and significantly greater improvement was observed when the surgical-treatment group was compared with the non-surgical-treatment group in terms of these two sensory and psychomotor functional testing outcomes at six weeks. Therapeutic study, Level II-1 (prospective cohort study). See Instructions to Authors for a complete description of levels of evidence.


An angiotensin I-converting enzyme mutation (Y465D) causes a dramatic increase in blood ACE via accelerated ACE shedding.
Angiotensin I-converting enzyme (ACE) metabolizes a range of peptidic substrates and plays a key role in blood pressure regulation and vascular remodeling. Thus, elevated ACE levels may be associated with an increased risk for different cardiovascular or respiratory diseases. Previously, a striking familial elevation in blood ACE was explained by mutations in the ACE juxtamembrane region that enhanced the cleavage-secretion process. Recently, we found a family whose affected members had a 6-fold increase in blood ACE and a Tyr465Asp (Y465D) substitution, distal to the stalk region, in the N domain of ACE. HEK and CHO cells expressing mutant (Tyr465Asp) ACE demonstrate a 3- and 8-fold increase, respectively, in the rate of ACE shedding compared to wild-type ACE. Conformational fingerprinting of mutant ACE demonstrated dramatic changes in ACE conformation in several different epitopes of ACE. Cell ELISA carried out on CHO-ACE cells also demonstrated significant changes in local ACE conformation, particularly proximal to the stalk region. However, the cleavage site of the mutant ACE--between Arg1203 and Ser1204--was the same as that of WT ACE. The Y465D substitution is localized in the interface of the N-domain dimer (from the crystal structure) and abolishes a hydrogen bond between Tyr465 in one monomer and Asp462 in another. The Y465D substitution results in dramatic increase in the rate of ACE shedding and is associated with significant local conformational changes in ACE. These changes could result in increased ACE dimerization and accessibility of the stalk region or the entire sACE, thus increasing the rate of cleavage by the putative ACE secretase (sheddase).


Improving statins production: From non-genetic strategies to genetic strategies.
Statins are lipid-lowering drugs that selectively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, effectively reducing cholesterol synthesis. With improved nutritional conditions, the demand for statins is increasing in the global market. The use of microbial cell factories for statin biosynthesis has become advantageous due to the rapid advancements in biotechnology. These approaches offer simple operation and easy separation of products. This review provides an overview the strategies for statins production via microbial cell factories, including both traditional fermentation culture (non-genetic) and modern synthetic biology manufacture (genetic). Firstly, the complex fermentation parameters and process control technology on submerged fermentation (SmF) and solid-state fermentation (SSF) are introduced in detail. The potential use of recoverable agricultural wastes/(biomass) as a fermentation substrate in SSF for statin production is emphasized. Additionally, metabolic engineering strategies for constructing robust engineering strains and directed evolution are also discussed. The review highlights the potential and challenges of using microbial cell factories for statin production, and aims to promote greener production modes for statins.


Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice.
Comparison of transcriptomic and proteomic data from pathologically similar multiple sclerosis (MS) lesions reveals down-regulation of CD47 at the messenger RNA level and low abundance at the protein level. Immunohistochemical studies demonstrate that CD47 is expressed in normal myelin and in foamy macrophages and reactive astrocytes within active MS lesions. We demonstrate that CD47(-/-) mice are refractory to experimental autoimmune encephalomyelitis (EAE), primarily as the result of failure of immune cell activation after immunization with myelin antigen. In contrast, blocking with a monoclonal antibody against CD47 in mice at the peak of paralysis worsens EAE severity and enhances immune activation in the peripheral immune system. In vitro assays demonstrate that blocking CD47 also promotes phagocytosis of myelin and that this effect is dependent on signal regulatory protein α (SIRP-α). Immune regulation and phagocytosis are mechanisms for CD47 signaling in autoimmune neuroinflammation. Depending on the cell type, location, and disease stage, CD47 has Janus-like roles, with opposing effects on EAE pathogenesis.


[PERFUSION TECHNOLOGIES IN TREATMENT OF PATIENTS WITH SKIN MELANOMA AND SOFT TISSUE SARCOMAS OF EXTREMITIES].
A steady increase of incidence of skin melanoma and soft tissue sarcomas of the extremities currently continues to be observed. Taking into account the high probability of developing of locally disseminated forms of skin melanoma and soft tissue sarcomas of extremities, the need to use combined methods in their treatment is quite high. In the 21st century the possibility of a use of isolated regional chemoperfusion provides a high objective response of tumor to chemotherapy without their systemic impact and improves the quality of life through preservation of the limb. This review describes the currently used drugs, and the results of ongoing clinical research in the world, as well as the results of our own study.


Mitochondrial genomes of the bird genus Piranga: rates of sequence evolution, and discordance between mitochondrial and nuclear markers.
We report the characteristics of the mitochondrial genomes of 22 individuals in the bird genus Piranga, including all currently recognized species in the genus (n = 11). Elements follow the standard avian mitogenome series, including two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, 13 protein coding genes, and the mitochondrial control region. Excluding tRNA sequences, sequence divergence rate was lowest in rRNA genes and highest in genes encoding NADH (specifically ND1, ND2, ND3) and the control region. Gene trees assembled from 16 elements (non-tRNAs) varied greatly in topological concordance compared to the recognized species tree (based on thousands of nuclear loci), with no one gene tree precisely recovering all relationships in the genus. We also investigated patterns of concordance between the mitogenome tree and the nuclear species tree and found some discrepancies. Across non-tRNA gene trees (n = 16), the species tree topology was recovered by as few as three elements at a particular node and complete concordance (i.e. 16/16 gene trees matched the species tree topology) was recovered at only one node. We found mitochondrial gene regions that are often used in vertebrate systematics (e.g. CytB, ND2) recovered nearly the exact same topology as the nuclear species tree topology.


Evaluation of the electrostatic field strength at the site of exocytosis in adrenal chromaffin cells.
Exocytosis in secretory cells consists of release from intracellular storage granules directly into the extracellular space via fusion of the granule membrane with the plasma membrane of the cell. It is considered here as comprising two distinct processes. One is the close apposition of granule and plasma membranes. The other arises from interactions between the two membranes during the process of apposition, leading to the formation of a fusion pore. In the following it is shown for the case of the adrenal medullary chromaffin cell that the fusion pore can be ascribed to electroporation of the granule membrane, triggered by the strong electric field existing at the site of exocytosis. Based on an electric surface charge model of the cytoplasmic side of the plasma membrane, resulting from the negatively charged phosphatidylserine groups, it is found that the electrostatic field strength at the site of exocytosis reaches values on the order of 10(8) V/m at small intermembrane distances of 3 nm and lower. The field strength increases with the size of the disc-shaped plasma membrane region generating the electric field, reaching an approximate limit for a radius of 10 nm, at a surface charge density of 5.4 x 10(-2) C/m2. According to previous experimental evaluations of threshold field strength, this field is sufficiently strong to cause membrane electroporation. This step is a precondition for the subsequent membrane fusion during the ongoing process of apposition, leading to secretion.


Sero diagnosis of hydatid disease.
Two serological test, double agar gel diffusion test (DD5T) and indirect haemagglutination test (IHAT) were performed for diagnosis of hydatid disease. Correlation of their results with eosinophilia were also made. DD5T gave higher sensitivity (100%) than IHAT which gave 95%. Out of the serologically positive patients, only 50% had eosinophilia. Sheep hydatid antigen was more potent than camel antigen. The supernatant lyophilized sheep antigen was the best antigen used.


Neurodegeneration and ageing in the HAART era.
Cognitive impairment and neurodegeneration still occur despite highly active antiretroviral therapy (HAART). While there are many potential reasons for this, there is increasing evidence that such impairment occurs in the absence of a clear cause. Furthermore, there are data that some neurodegenerative diseases, especially Alzheimer's or an Alzheimer-like illness, are becoming more common in the context of HAART-treated human immunodeficiency virus (HIV) disease. This review will critically examine the evidence underpinning these observations. Potential mechanisms will be discussed with particular emphasis on the effect of ageing and how it overlaps with the effects of HIV disease itself thereby leading to neurodegeneration. The nature of this overlap will then be explored for its potential role in the facilitated expression and development of neurodegenerative diseases. Lastly, there will be a brief discussion of interventions to minimize such neurodegeneration including optimization of HAART for brain entry.