The anesthetic agent as an extra-integumentary foreign body in the respiratory tract. A new theory of general anesthesia.
Two cases are cited of patients who sometimes exhibited a condition of temporary unconsciousness which proceeded to spontaneous recovery without harmful sequelae. This type of cerebral arrest is frequently called general anesthesia:however, these patients had not received any drugs. What they did have was an irritant in the respiratory passages as shown by coughing. Three cases of general anesthesia are described wherein the duration of the phenomenon appeared to be partly due to the presence of an extra-integumentary foreign body, confined to the respiratory passages. In this trio there was evidence that the drugs did not affect the patients in any unusual way, whatever their effects on whichever side of the alveolar walls. Many anesthetic agents act like unabsorbable foreign bodies, in that they enter and leave the body unchanged, despite the fact that they do pierce the integument. Of course, almost everything, except inspirable and expirable air, but including anesthetic agents, is a foreign body in the respiratory tract. On the basis of these considerations, I suggest that one way, in which general anesthetic agents work, is an extra-integumentary foreign bodies, causing Reflex Coma by irritating or stimulating the trigger points in the walls of the respiratory tract, thereby arresting the cerebrum.


How will I be after my operation for oral cancer?
Validated health-related quality of life measures for patients with oral cancer have been available for over a decade. We used the Liverpool head and neck cancer database to identify 1060 patients who had curative operations for primary squamous cell carcinoma of the head and neck at the regional maxillofacial unit between 1995 and 2010. We then produced one-page summary tables for subsites of oral cancer by stage and common treatments based on patient-reported outcomes from the University of Washington quality of life (UWQoL) head and neck cancer questionnaire. Data had been collected in a series of annual surveys. Sites included were buccal and retromolar (n=189), oral tongue (n=358), floor of the mouth (n=321), and other oral sites (n=192). A total of 633 patients completed at least one questionnaire (total 1931) between 9 and 60 months after treatment (71% of those alive at 9 months). Only questionnaires completed around 2 years from diagnosis or operation were analysed. Data include crude survival at 1, 2, and 5 years, the 12 UWQoL domains, which comprise the number of patients who chose the best 2 responses for each, overall health-related QoL, and the number who chose the worst responses (based on an algorithm). The data are sufficiently detailed to be used in discussions with patients about likely outcomes. They can help patients to make decisions about the type of treatment, provide a reference for realistic expectations, and enable them to be better informed when they give their consent.


Para niños saludables: a community intervention trial to reduce organophosphate pesticide exposure in children of farmworkers.
Exposure to organophosphate (OP) pesticides is an occupational hazard for farmworkers and affects their children through the take-home pathway. We examined the effectiveness of a randomized community intervention to reduce pesticide exposure among farmworkers and their children. We conducted a baseline survey of a cross-sectional sample of farmworkers (year 1) in 24 participating communities. Communities were randomized to intervention or control. After 2 years of intervention, a new cross-sectional survey of farmworkers was conducted (year 4). Farmworkers with a child 2-6 years of age were asked to participate in a substudy in which urine was collected from the farmworker and child, and dust was collected from the home and the vehicle driven to work. The median concentration of urinary metabolites was higher in year 4 than in year 1 for dimethylthiophosphate (DMTP) and dimethyldithiophosphate in adults and for DMTP for children. There were significant increases within both the intervention and control communities between year 1 and year 4 (p < 0.005); however, the differences were not significant between study communities after adjusting for year (p = 0.21). The dust residue data showed azinphos-methyl having the highest percentage of detects in vehicles (86% and 84% in years 1 and 4, respectively) and in house dust (85% and 83% in years 1 and 4, respectively). There were no significant differences between intervention and control communities after adjusting for year (p = 0.49). We found no significant decreases in urinary pesticide metabolite concentrations or in pesticide residue concentrations in house and vehicle dust from intervention community households compared with control community households after adjusting for baseline. These negative findings may have implications for future community-wide interventions.


Endothelial nitric oxide synthase gene intron 4 polymorphism in non-traumatic osteonecrosis of the femoral head.
Nitric oxide (NO) synthesised by endothelial NO synthase (eNOS) is a potent regulator of internal haemodynamics. A polymorphism in intron 4 of the eNOS is associated with different vascular disorders. We investigated the potential involvement of this polymorphism in idiopathic and secondary osteonecrosis of the femoral head (ONFH) in Polish patients. We performed a study involving 68 patients with ONFH (45 idiopathic and 23 secondary) and 100 healthy controls. All subjects were genotyped for the eNOS4 polymorphism by the polymerase chain reaction followed by agarose gel electrophoresis. The analysis revealed that the frequencies of eNOS4 genotypes were significantly different in ONFH patients (both idiopathic and secondary) than in controls. The frequencies of the 4a allele were significantly higher in the total group of patients versus controls [22.79 vs 9%, p = 0.00039, odds ratio (OR) 2.98]. In subgroup analysis the 4a allele increased significantly in both idiopathic (20 vs 9%, p = 0.0074, OR = 2.52) and secondary (28.26 vs 9%, p = 0.00047, OR = 3.98) ONFH patients compared to control subjects. The frequency of the 4a/b genotype in the total group of patients (36.76 vs 16%, p = 0.0011, OR = 3.24) as well as patients with idiopathic (35.56 vs 16%, p = 0.0069, OR = 2.96) and secondary (39.13 vs 16 %, p = 0.0073, OR = 3.89) ONFH was higher than in the control group. There was a significantly higher frequency of eNOS 4a allele carriers among the total group of patients as well as in idiopathic and secondary ONFH. This suggests that the eNOS gene polymorphism may be associated with increased risk of ONFH.


High-efficient capture and degradation of formaldehyde based on the electric-field-enhanced catalytic effect.
Enhancing the generation of active groups is of great significance for alleviating the catalyst deactivation of formaldehyde (HCHO) by accelerating the decomposition of intermediate products. Herein, an electric-field-enhanced catalytic effect was proposed for the efficient capture and degradation of HCHO base on carbon cloth loaded manganese oxide catalyst (MnOx-CC). Under the action of electric field, MnOx can generate more hydroxyl radicals (•OH) and superoxide radicals (•O2-), thus accelerating the degradation of HCHO and intermediates at room temperature. After the introduction electric field (∼1 ×104 V/m), •O2- and •OH radical on the surface of MnOx-CC catalyst can be increased by 8 times and 23 times, respectively. At weight hourly space velocity of 300,000 mL/(gcat h) for ∼15 ppm HCHO, MnOx-CC-Electric Field catalyst reached the removal efficiency of 99.4%, and the CO2 conversion efficiency of 81.2%, without decrease significantly within 80 h. Theoretical calculation shows that the electric field can increase the electron state density of Mn atom at the Fermi level and reduce the adsorption energy of HCHO, O2 and H2O, thus promoting the generation of active groups and degradation of intermediate products. The electric-field-enhancement catalytic effect provides a new approach for the degradation of Volatile Organic Compounds.


Carcinomatous meningitis as a clinical manifestation of pancreatic carcinoma.
Carcinomatous meningitis (CM) is clinically less common than brain metastasis or spinal cord compression, having dire consequences for both the quality of life and the overall survival of patients with solid tumors. It occurs in about 5% of all adult cancer patients, but autopsies may double this number. If leukemia and lymphoma are excluded, most cases are due to breast cancer, lung cancer and melanoma. In this report, we describe a 49-year-old male patient with metastatic pancreatic adenocarcinoma who developed carcinomatous meningitis. To our knowledge, this is only the second case of carcinomatous meningitis secondary to a pancreatic carcinoma described so far.


The SOS Chromotest, a colorimetric bacterial assay for genotoxins: validation study with 83 compounds.
The SOS Chromotest is a simple bacterial colorimetric assay for genotoxicity. It is based on the measure of the induction of sfiA, a gene controlled by the general repressor of the SOS system in E. coli. Expression of sfiA is monitored by means of a gene fusion with lacZ, the structural gene for beta-galactosidase. We have examined 83 compounds of various chemical classes with the SOS Chromotest using a standard procedure. Comparison of the results with those obtained in the Mutatest (the Ames test) showed that most (90%) of the mutagenic compounds were also SOS inducers. For these compounds a quantitative correlation was observed between the mutagenic potency and the SOS-inducing potency (SOSIP). The case of the 10% remaining compounds giving conflicting results in the two tests is discussed. Sensitivity, specificity and accuracy for carcinogenicity prediction have been evaluated for the SOS Chromotest and the Mutatest using 73 chemicals for which carcinogenicity data were available. In spite of some differences, similar results were obtained in the two tests. The present data indicate that the SOS Chromotest has many practical advantages and may be used as a primary screening tool or as part of a battery of short-term tests for carcinogens.


Does position of syndesmotic screw affect functional and radiological outcome in ankle fractures?
The optimum level of syndesmotic screw used in ankle fractures with a tibiofibular diastasis is not clear in the literature. In a retrospective cohort study, we evaluated the clinical and radiological outcomes in two groups of patients-those who had a syndesmotic screw placed through the syndesmosis itself (transsyndesmotic, 17 patients) and those who had a syndesmotic screw placed just above the syndesmosis (suprasyndesmotic, 19 patients). The study suggests that the two groups do not differ significantly in terms of clinical and radiological outcomes.


Evaluation of transmembrane domain deletions on hyaluronic acid polymerization of hyaluronan synthase isolated from Streptococcus equisimilis group G.
The membrane enzyme of hyaluronan synthase (HAS) is the key enzyme in hyaluronic acid (HA) biosynthesis by coupling UDP-sugars. Prior studies proposed the C-terminus region of HAS enzyme mediates the production rate and molecular weight of HA. The current study describes the isolation and characterizations of a transmembrane HAS enzyme isolated from Streptococcus equisimilis Group G (GGS-HAS) in vitro. The effect of transmembrane domains (TMDs) on HA productivity was determined and the shortest active variant was also identified by recombinant expression of full-length and five truncated forms of GGS-HAS in Escherichia coli. We found that the GGS-HAS enzyme is longer than that of S. equisimilis group C (GCS-HAS) which includes three more residues (LER) at the C-terminus region (positions 418-420) and also one-point mutation at position 120 (E120D). Amino acid sequence alignment demonstrated 98% and 71% identity of GGS-HAS with that of S. equisimilis Group C and S. pyogenes Group A, respectively. The in vitro productivity of the full-length enzyme was 35.57 µg/nmol, however, extended TMD deletions led to a reduction in the HA productivity. The HAS-123 variant showed the highest activity among the truncated forms, indicating the essential role of first, second, and third TMDs for the full activity. Despite a decline in activity, the intracellular variant can still mediate the binding and polymerization of HA without any need for TMDs. This significant finding suggests that the intracellular domain is the core for HA biosynthesis in the enzyme and other domains are probably involved in other attributes including the enzyme kinetics that affect the size distribution of the polymer. However, more investigations on the recombinant forms are still needed to confirm clearly the role of each transmembrane domain on these properties.


Current Treatment Options: Vestibular Migraine.
Vestibular migraine (VM) is a disorder with a spectrum of clinical presentations and among the most common causes of chronic vestibular symptoms. Some present with attacks before or during typical migraine, but many others have fluctuating or daily symptoms. While the symptoms and pathogenesis of vestibular migraine may have elements of both central and peripheral disorders, hearing loss should be absent. VM typically worsens with activity and head movements in general, and encompasses symptoms of vertigo, disequilibrium, or imbalance. While it is possible to confuse other disorders such as Meniere's disease with migraine, it is worth making the diagnosis of vestibular migraine on clinical grounds after ruling out other possible causes. For acute attack treatment, migraine-specific medications such as triptans may be effective. In patients with frequent or disabling attacks, preventive treatment is essential. Vestibular rehabilitation may be helpful as well as medications used for migraine prevention such as including propranolol, venlafaxine, topiramate, and amitriptyline. For refractory patients, use of acetazolamide or lamotrigine may be reasonable.


The effects of age bias on neural correlates of successful and unsuccessful response inhibition in younger and older adults.
Facilitating communication between generations has become increasingly important. However, individuals often demonstrate a preference for their own age group, which can impact social interactions, and such bias in young adults even extends to inhibitory control. To assess whether older adults also experience this phenomenon, a group of younger and older adults completed a Go/NoGo task incorporating young and old faces, while undergoing functional magnetic resonance imaging. Within the networks subserving successful and unsuccessful response inhibition, patterns of activity demonstrated distinct neural age bias effects in each age group. During successful inhibition, the older adult group demonstrated significantly increased activity to other-age faces, whereas unsuccessful inhibition in the younger group produced significantly enhanced activity to other-age faces. Consequently, the findings of the study confirm that neural responses to successful and unsuccessful inhibition can be contingent on the stimulus-specific attribute of age in both younger and older adults. These findings have important implications in regard to minimizing the emergence of negative consequences, such as ageism, as a result of related implicit biases.


Extended-spectrum beta-lactamase production and multi-drug resistance among Enterobacteriaceae isolated in Addis Ababa, Ethiopia.
The global emergence and spread of extended-spectrum beta-lactamases (ESBLs) producing Enterobacteriaceae have been threatening the ability to treat an infection. Hence, this study aimed to determine the prevalence of ESBL-producing and multi-drug resistance (MDR) Enterobacteriaceae (ESBLs-E) from different clinical specimens in Addis Ababa, Ethiopia. A cross-sectional study was conducted from January 1 to May 30, 2017. A total of 426 Enterobacteriaceae isolates were identified from clinical specimens. The isolates were collected from four laboratories. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method on Muller Hinton agar (MHA). All Enterobacteriaceae were screened for ESBLs production using cefotaxime and ceftazidime as per CLSI guideline. Each ESBL screening positive Enterobacteriaceae were confirmed by a combination disk test (CDT). Data were entered and analyzed by using SPSS version-20. The most frequent Enterobacteriaceae were E. coli 228 (53.5%) and K. pneumoniae 103 (24.1%). The magnitude of ESBLs-E was 57.7% (246/426). The highest frequencies of ESBLs-E were observed in blood specimesns (84.4%) and the highest ESBLs production was observed in K. pneumoniae (85.4%). The highest resistance level was seen to sulfamethoxazole-trimethoprim (77.0%), amoxicillin with clavulanic acid (71.6%), cefotaxime (62.2%), cefepime (60.3%) and ceftazidime (60.8%). The overall magnitude of multi-drug resistance (MDR) level was 68.3%. Of ESBLs-E, 96.3% of them were MDR (P < 0.001). There was a high prevalence of ESBLs-E and MDR isolate in Addis Ababa. Most of ESBLs-E was isolated primarily in blood and urine. The highest ESBLs production was observed among K. pneumoniae. Hence, strong infection control strategies must be implemented in hospital settings of the country.


Monitoring of oil spill in the offshore zone of the Nile Delta using Sentinel data.
This study aims to monitor and map the oil spills which occurred from 2019 to 2021 along the northeastern portion of the Nile Delta using Sentinel-1 (SAR) and Sentinel-2 (MSI) data. The examination of VV polarized SAR-C images displayed the presence of the oil spills as dark spots of different sizes. These images were processed using the oil spills detection model in SNAP Toolbox. The oceanographic parameters that may influence the dispersal of oil spills were mapped using GIS technique. This study identified 29 oil spills during the study period in the research area. The largest spill was detected on February 23, 2019, and covered an area of about 10.5 km2. The band ratios and decorrelation stretch methods of available Sentinel-2 data confirmed the results of SAR-C data. The accuracy assessment of spills was achieved using Parallelepiped supervised classification model. The results demonstrated that the overall accuracy (OA) and Kappa coefficient (KC) for seawater, land, and oil spills classes were between 86% and 98% and 0.73% and 0.97%, respectively. The sensitivity zone of oil spills was higher in winter than in summer. This study proved the efficiency of VV polarized data of Sentinel-1 sensor for detection and mapping of oil spills. Several management strategies are needed in the offshore zone of the Nile Delta to limit oil pollution effects on the marine environment.


Surgical treatment of persistent fifth aortic arch associated with interrupted aortic arch.
This study describes two cases of the rare congenital anomaly, persistent fifth aortic arch. Both cases involve boys (1 at 9 years of age and another at 7 months of age). To detect persistent fifth aortic arch with interrupted aortic arch, the following methods were used: echocardiogram, angiocardiography, and magnetic resonance imaging. In both cases the blood pressure between the upper and lower limbs differed. To relieve the obstruction of blood flow, each case was surgically repaired using patching or conduit interposition. Postoperative courses were uneventful. Two-year to 5-year follow-up examinations were positive showing that the anastomosis was unobstructed and the velocity of blood flow to the descending aorta was normal.


Changes in mucosal fatty acid profile in inflammatorybowel disease and in experimental colitis: a common response to bowel inflammation.
Plasma polyunsaturated fatty acid profile in patients with inflammatory bowel disease is abnormal. We aimed to assess the mucosal fatty acid pattern in patients with ulcerative colitis and Crohn's disease, and in rats with trinitrobenzene-sulfonic acid (TNB) induced colitis. Fatty acids were measured in colonic mucosa of patients with ulcerative colitis (n = 30), Crohn's disease (n = 21), and healthy controls (n = 13). Likewise, they were assessed in the colonic mucosa of rats with TNB- and sham-colitis. There was an increase of the end-products (C22:5n3, C22:6n3, C20:4n6, C22:5n6) and a decrease of the precursors (C18:3n3, C18:2n6) of both n3 and n6 polyunsaturated fatty acids in the mucosa of active ulcerative colitis and TNB-colitis. Also, high values of saturated (C16:0, C18:0) and low values of monounsaturated fatty acids (C18:1n9) were observed. Furthermore, the mucosa of active Crohn's disease showed substantial changes in saturated, monounsaturated and essential fatty acids, but not in polyunsaturated fatty acids. Mucosa of patients with inactive disease showed intermediate fatty acid values between the mucosa of active patients and healthy controls. Colonic inflammation causes a characteristic modification of the mucosal fatty acid profile which appears to be common to different aetiologies and seems to be related to the degree of inflammation.


Validation of Microarray for the Simultaneous Detection of Common α- and β-Thalassemia Gene Mutations.
Methods for detecting the complex genetic characteristics of α- and β-thalassemias are required for preventing and controlling the outbreak of new cases. We evaluated the accuracy and practical utility of microarray for simultaneous detection of α- and β-thalassemias. A total of 102 DNA specimens, which represented 25 different genotypes, were tested in parallel using the microarray and reference methods used in the thalassemia laboratory of the Associated Medical Sciences-Clinical Services Center (AMS-CSC), Chiang Mai, Thailand. A total of 100 (98.0%) DNA specimens were completely concordant between the microarray and reference methods, whereas discrepancies between the different methods were observed in only 2 DNA specimens with homozygous hemoglobin E (HbE). The microarray appeared to be a fast, easy to perform, and accurate method for simultaneous detection of α- and β-thalassemias in Thailand and Southeast Asian countries. However, this technique needs to be improved and validated in a larger number of specimens with homozygous HbE before further routine laboratory use.


Efficacy and tolerance of fluocortin butyl administered twice daily in adult patients with perennial rhinitis.
Fluocortin butyl (FCB) is a newly developed corticosteroid drug with no detectable systemic corticosteroid activity when it is used topically. Previous studies have demonstrated the therapeutic efficacy of FCB applied topically to the nasal mucosa three to four times a day for perennial rhinitis. The therapeutic efficacy of FCB used only twice daily, with total daily dosages similar to those previously found to be effective when these were applied more frequently, was studied in a multicenter, double-blind, placebo-controlled trial. This was a 4-week study with a 1-week observation (baseline) period and a 3-week period during which the response to three dosage regimens (2 mg per day, 4 mg per day, and 8 mg per day) of FCB and placebo were compared to baseline observations of rhinitis. Two hundred thirty-five patients from six centers were studied. Patients had perennial rhinitis of allergic, nonallergic, or combined etiology. Patients who received FCB exhibited significant amelioration of signs and symptoms of rhinitis as assessed by patients and physicians and had a greater reduction in the use of concomitant antihistamine and/or decongestant therapy compared to placebo-treated patients. Relief tended to occur early and was progressive during the 3 wk of therapy. There were no significant differences in response between the various dosages of FCB used. Side effects were minimal and insignificant and did not differ between FCB-treated and placebo-treated patients. FCB appears to be an effective well-tolerated topical steroid useful in the treatment of perennial rhinitis.


Evidence of foveal splitting in a commissurotomy patient.
A bilateral projection of the central fovea, produced by naso-temporal overlap at the retinal vertical meridian, has been proposed as the anatomical basis of macular sparing. To evaluate this claim, a commissurotomy patient was required to compare target figures presented 1 degrees or less from the retinal midline with reference figures presented 2.5 degrees from the midline in the same or opposite visual field. The subject judged whether the target and reference were the same or different. It was found that the subject's fovea was effectively split with respect to the cerebral hemispheres; targets in the same visual field as the reference were readily matched with the reference, but accuracy dropped to chance for targets in the opposite field. Ways of reconciling this data with anatomical evidence of nasotemporal overlap and reports of macular sparing are discussed.


Lifestyle-related risk factors and their cumulative associations with hippocampal and total grey matter volume across the adult lifespan: A pooled analysis in the European Lifebrain consortium.
Lifestyle-related risk factors, such as obesity, physical inactivity, short sleep, smoking and alcohol use, have been associated with low hippocampal and total grey matter volumes (GMV). However, these risk factors have mostly been assessed as separate factors, leaving it unknown if variance explained by these factors is overlapping or additive. We investigated associations of five lifestyle-related factors separately and cumulatively with hippocampal and total GMV, pooled across eight European cohorts. We included 3838 participants aged 18-90 years from eight cohorts of the European Lifebrain consortium. Using individual person data, we performed cross-sectional meta-analyses on associations of presence of lifestyle-related risk factors separately (overweight/obesity, physical inactivity, short sleep, smoking, high alcohol use) as well as a cumulative unhealthy lifestyle score (counting the number of present lifestyle-related risk factors) with FreeSurfer-derived hippocampal volume and total GMV. Lifestyle-related risk factors were defined according to public health guidelines. High alcohol use was associated with lower hippocampal volume (r = -0.10, p = 0.021), and overweight/obesity with lower total GMV (r = -0.09, p = 0.001). Other lifestyle-related risk factors were not significantly associated with hippocampal volume or GMV. The cumulative unhealthy lifestyle score was negatively associated with total GMV (r = -0.08, p = 0.001), but not hippocampal volume (r = -0.01, p = 0.625). This large pooled study confirmed the negative association of some lifestyle-related risk factors with hippocampal volume and GMV, although with small effect sizes. Lifestyle factors should not be seen in isolation as there is evidence that having multiple unhealthy lifestyle factors is associated with a linear reduction in overall brain volume.


The characterization of collagen-based scaffolds modified with phenolic acids for tissue engineering application.
The aim of the experiment was to study the morphology of collagen-based scaffolds modified by caffeic acid, ferulic acid, and gallic acid, their swelling, and degradation rate, as well as the biological properties of scaffolds, such as antioxidant activity, hemo- and cytocompatibility, histological observation, and antibacterial properties. Scaffolds based on collagen with phenolic acid showed higher swelling rate and enzymatic stability compared to scaffolds based on pure collagen, and the radical scavenging activity was in the range 85-91%. All scaffolds were non-hemolytic and compatible with surrounding tissues. Collagen modified by ferulic acid showed potentially negative effects on hFOB cells as a significantly increased LDH release was found, but all of the studied materials had antimicrobial activity against Staphylococcus aureus and Escherichia coli. It may be assumed that phenolic acids, such as caffeic, ferulic, and gallic acid, are modifiers and provide novel biological properties of collagen-based scaffolds. This paper provides the summarization and comparison of the biological properties of scaffolds based on collagen modified with three different phenolic acids.


Differential effects of AGS3 expression on D(2L) dopamine receptor-mediated adenylyl cyclase signaling.
Activator of G protein signaling 3 (AGS3) binds Gα(i) subunits in the GDP-bound state, implicating AGS3 as an important regulator of Gα(i)-linked receptor (e.g., D2 dopamine and μ-opioid) signaling. We examined the ability of AGS3 to modulate recombinant adenylyl cyclase (AC) type 1 and 2 signaling in HEK293 cells following both acute and persistent activation of the D(2L) dopamine receptor (D(2L)DR). AGS3 expression modestly enhanced the potency of acute quinpirole-induced D(2L)DR modulation of AC1 or AC2 activity. AGS3 also promoted desensitization of D(2L)DR-mediated inhibition of AC1, whereas desensitization of D(2L)DR-mediated AC2 activation was significantly attenuated. Additionally, AGS3 reduced D(2L)DR-mediated sensitization of AC1 and AC2. These data suggest that AGS3 is involved in altering G protein signaling in a complex fashion that is effector-specific and dependent on the duration of receptor activation.


Pharmacokinetics, dosimetry and comparative efficacy of 188Re-liposome and 5-FU in a CT26-luc lung-metastatic mice model.
The biodistribution, pharmacokinetics, dosimetry and comparative therapeutic efficacy of intravenously administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposome ((188)Re-liposome) and 5-FU were investigated in a CT26-luc lung-metastatic model. After intravenous administration of (188)Re-liposome, tumor accumulation from the radioactivity was observed. Levels of radioactivity in tumors were maintained at steady levels (from 5.40 to 5.67 %ID/g) after 4 to 24 h. In pharmacokinetics, the AUC((0→∞)), MRT((0→∞)) and Cl of (188)Re-liposome in blood via intravenous route were 998 h %ID/ml, 28.7 h and 0.1 ml/h, respectively. The total excreted fractions of feces and urine were 0.61 and 0.26, respectively. Absorbed doses for (188)Re-liposome in the liver and red marrow were 0.31 and 0.08 mSv/MBq, respectively. Tumor-absorbed doses for (188)Re-liposome ranged from 48.4 to 1.73 mGy/MBq at 10 to 300 g tumor spheres. In therapeutic efficacy, the survival times of mice after (188)Re-liposome [80% maximum tolerated dose (MTD); 29.6 MBq], 5-FU (80% MTD; 144 mg/kg), liposome or normal saline treatments were evaluated. Consequently, radiotherapeutics of (188)Re-liposome attained a longer lifespan (increase of 34.9%; P=.005) in mice than in the normal saline group. The increase in lifespan of the (188)Re-liposome group was 2.5-fold greater than that of the 5-FU group. Therefore, intravenous administration of (188)Re-liposome could provide a benefit and it is a promising strategy for delivery of passive nanotargeted radiotherapeutics in oncology applications.


Insecticidal bacteria: an overwhelming success for invertebrate pathology.
The discovery and study of insecticidal bacteria, which began a little over a century ago, led to the development of commercial bacterial insecticides in the middle of the century that became the first successful and widely used microbial control agents. Most of these products were based on Bacillus thuringiensis, a bacterium that kills insects through the use of insecticidal proteins that subsequently became known as Cry proteins. While most of these products were only effective against lepidopteran pests, their success eventually led in the 1970s and 1980s to the discovery of strains effective against larvae of coleopteran pests and nematocerous dipterans, such as vector and nuisance mosquitoes and blackflies. The cloning in 1981 of the first gene encoding a Cry protein led to an explosion of basic and applied research that culminated in new strains of recombinant insecticidal bacteria and, even more importantly, the development, commercialization, and wide-scale deployment of insecticidal transgenic crops based on Cry proteins. This new and environmentally safe technology has revolutionized agricultural pest control, yielding a multibillion dollar industry that is paving the way to new types of plants that will dominate food and fiber production as the 21st century progresses. In this brief symposium paper, I provide an overview of some of the key work that led to this remarkable success.


Foraging rhythm of great crested grebes Podiceps cristatus adjusted to diel variations in the vertical distribution of their prey Osmerus eperlanus in a shallow eutrophic lake in The Netherlands.
Great crested grebes Podiceps cristatus only foraged for an hour or two during dawn and again during dusk on Lake IJsselmeer in August-September. During this time of the year the adult birds are in wing moult and temporarily unable to fly. The food of grebes consisted almost exclusively of smelt Osmerus eperlanus, the most numberous pelagic fish. Simultaneous sonar registrations and trawl net fishing showed that smelt moved to the water surface during the twilight periods. During day and night they were concentrated near the bottom. We argue that grebes have the best foraging opportunities during twilight when much of their prey is near the surface, where light intensities allow the fish to be detected and captured. When the smelt are in the upper water layers the distance to the covered to get the prey (i.e. diving time and cost) is also least.


Prognostic value of final pathological stage in colon adenocarcinoma after neoadjuvant chemotherapy: A propensity score-matched study.
Neoadjuvant chemotherapy (NAC) could improve local tumor control of locally advanced colon cancer (LACC), but the prognostic value of yp stage in colon cancer remains unknown. Here, we aimed to ascertain yp stage as an indicator for LACC prognosis after NAC. The data of patients diagnosed with colon adenocarcinoma between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results database. After 1:2 propensity score matching, cancer-specific survival (CSS) and overall survival (OS) were compared between the NAC and Non-NAC groups of different stage classifications. The correlation between clinical and pathological factors and CSS was identified. A total of 49, 149, and 81 matched pairs of stage 0-I, II, and III patients, respectively, were generated for analysis. For stage 0-I (p = 0.011) and III (p = 0.015), only CSS in the NAC groups were inferior. Receiving NAC was an independent prognostic risk factor for patients with stage 0-I (hazard ratio, 7.70; 95% confidence interval, 1.820-32.5; p = 0.006) and stage III (hazard ratio, 1.73; 95% confidence interval, 1.11-2.68; p = 0.015). The CSS was poorer among LACC patients who underwent NAC than among those who did not. The yp stage of colon cancer after NAC has distinctive significance, which may contribute to predicting the prognosis and guiding the treatment of LACC patients after NAC.


Conservative therapy versus arthroscopic surgery of femoroacetabular impingement syndrome (FAI): a systematic review and meta-analysis.
FAI (femoroacetabular impingement syndrome) is a common cause of hip pain, resulting in a decreased life quality. This study aims to compare the postoperative clinical outcome between arthroscopic surgery (AT) and conservative treatment (CT). The six studies were selected from PubMed, Embase and OVID database. The data were extracted and analyzed by RevMan5.3. Mean differences and 95% confidence intervals were calculated. RevMan5.3 was used to assess the risk of bias. Six observational studies were assessed. The methodological quality of the trials indicated five of six studies had a low risk of bias and one article had a high risk of bias. The differences were statistically significant between AT and CT for HOS (follow-up for 6 months), iHOT-33 (follow-up for 6 months) improvement, iHOT-33 (follow-up for 12 months) improvement, iHOT-33 (follow-up for 12 months), EQ-5D-5L index score (follow-up for 12 months) and AT showed higher benefits than CT. Meanwhile no statistically significant were found in iHOT-33 (follow-up for 6 months), EQ-5D-5L index score (follow-up for 6 months), EQ5D-VAS (follow-up for 6 months) and EQ5D-VAS (follow-up for 12 months). AT and CT both can have clinical effects when facing FAI. In our meta-analysis, hip arthroscopy is statistically superior to conservative treatment in both long-term and short-term effects.


Development of an automated multi-injection shotgun lipidomics approach using a triple quadrupole mass spectrometer.
Shotgun lipidomics is a well-suited approach to monitor lipid alterations due to its ability to scan for varying lipid types on a global, class and individual species level. However, the ability to perform high-throughput shotgun lipidomics has remained challenging due to time-consuming data processing and hardware limitations. To increase the throughput nature of shotgun lipidomics, an automated shotgun lipidomics approach is described utilizing conventional low flow gradient liquid chromatography (LC) analysis (post-injection) coupled with multiple sample injections per sample (on a lipid scan per injection basis). The proposed automated multi-injection approach resulted in a reproducible lipid scanning period of 2.5 min (in a 4.5 min total data acquisition period), thereby providing a sufficient scanning period for performing either mass spectrometric or tandem mass spectrometric analyses. In addition to being simple, robust and reproducible, this approach was also constructed to be cost-effective by using common LC instrumentation and customizable as the data acquisition period can be tailored to perform different scan types, period lengths and scan numbers. Combined with a strategy to create multiple lipid-specific aliquots per sample, the overall approach provides a simple and efficient platform to perform high-throughput lipid profiling.


Sepsis and Septic Shock in the Equine Neonate.
Sepsis and septic shock represent a major cause of morbidity and mortality in equine neonates and in all species. Early recognition of the condition is important, but definitive examination and laboratory variables to predict equine neonatal sepsis are lacking. Early and aggressive treatment should include broad-spectrum antimicrobial coverage, source control, and hemodynamic support. Field practitioners and intensive care clinicians work together in the management of this condition because the recognition and initial treatment should begin as early as possible.


A novel defensin from the lentil Lens culinaris seeds.
A novel 47-residue plant defensin was purified from germinated seeds of the lentil Lens culinaris by ammonium sulfate precipitation, gel filtration, chromatography, and RP-HPLC. The molecular mass (5440.41Da) and complete amino acid sequence (KTCENLSDSFKGPCIPDGNCNKHCKEKEHLLSGRCRDDFRCWCTRNC) of defensin, termed Lc-def, were determined. Lc-def has eight cysteines forming four disulfide bonds. The total RNA was isolated from lentil germinated seeds, RT-PCR and subsequent cloning were performed, and cDNA was sequenced. A 74-residue predefensin contains a putative signal peptide (27 amino acid) and a mature protein. Lc-def shows high sequence homology with legumes defensins, exhibits an activity against Aspergillus niger, but does not inhibit proteolytic enzymes.


Enriching Traditional Protein-protein Interaction Networks with Alternative Conformations of Proteins.
Traditional Protein-Protein Interaction (PPI) networks, which use a node and edge representation, lack some valuable information about the mechanistic details of biological processes. Mapping protein structures to these PPI networks not only provides structural details of each interaction but also helps us to find the mutual exclusive interactions. Yet it is not a comprehensive representation as it neglects the conformational changes of proteins which may lead to different interactions, functions, and downstream signalling. In this study, we proposed a new representation for structural PPI networks inspecting the alternative conformations of proteins. We performed a large-scale study by creating breast cancer metastasis network and equipped it with different conformers of proteins. Our results showed that although 88% of proteins in our network has at least two structures in Protein Data Bank (PDB), only 22% of them have alternative conformations and the remaining proteins have different regions saved in PDB. However, using even this small set of alternative conformations we observed a considerable increase in our protein docking predictions. Our protein-protein interaction predictions increased from 54% to 76% using the alternative conformations. We also showed the benefits of investigating structural data and alternative conformations of proteins through three case studies.


Gamma-hydroxybutyrate hyperpolarizes hippocampal neurones by activating GABAB receptors.
gamma-Hydroxybutyrate, a naturally occurring substance present in the mammalian central nervous system caused a dose-dependent (0.25-10 mM) hyperpolarization and small membrane conductance increase when applied to hippocampal CA1 pyramidal neurones in vitro. This action was reversibly inhibited by the GABAB antagonist, CGP 35348 (20-100 microM) and divalent cations, Zn2+ and Ba2+, but not by the GABAA antagonist bicuculline (50 microM). These results suggest that GABAB receptors may mediate the actions of gamma-hydroxybutyrate.


The development of peptide-containing neurons within neocortical transplants in adult mice.
Transplantation of embryonic neocortex into adult host neocortex leads to the survival of many donor cells, with the subsequent differentiation of the cortical neurons within a loosely laminated cellular pattern. We wanted to know whether peptide-containing neurons that are known to exist in normal neocortex would survive in the transplants, and if so, whether they would differentiate into morphological cell types that normally contain these peptides in cortex. By 30 days after transplantation, the implants were well vascularized and the donor neurons appeared healthy in Nissl-stained preparations. AChE-positive axons grew across the interface and innervated the transplant in moderate densities. Immunocytochemical localization of peptides in the transplant revealed that processes containing the four peptides normally present in cortex also develop in the transplants. These were vasoactive intestinal polypeptide, cholecystokinin, pancreatic polypeptide and somatostatin. Other peptides not yet demonstrated in and presumably not present in neocortex, did not develop in the transplants. These included alpha-melanocyte stimulating hormone, arginine-vasopressin, corticotropin releasing factor, beta-endorphin and substance P. The results demonstrate that peptide-immunoreactive neurons survive in neural transplants, where they develop complicated patterns of axonal arborization. The conditions used in these experiments produced no evidence that peptidergic neurons within the transplant grow out of the transplant and into the host brain within six weeks. Similarly, host peptidergic axons were never seen crossing the interface zone and entering the transplant in any significant numbers.


Investigation of the metabolic consequences of impregnating spinach leaves with trehalose and applying a pulsed electric field.
The impregnation of leafy vegetables with cryoprotectants using a combination of vacuum impregnation (VI) and pulsed electric fields (PEF) has been proposed by our research group as a method of improving their freezing tolerance and consequently their general quality after thawing. In this study, we have investigated the metabolic consequences of the combination of these unit operations on spinach. The vacuum impregnated spinach leaves showed a drastic decrease in the porosity of the extracellular space. However, at maximum weight gain, randomly located air pockets remained, which may account for oxygen-consuming pathways in the cells being active after VI. The metabolic activity of the impregnated leaves showed a drastic increase that was further enhanced by the application of PEF to the impregnated tissue. Impregnating the leaves with trehalose by VI led to a significant accumulation of trehalose-6-phosphate (T6P), however, this was not further enhanced by PEF. It is suggested that the accumulation of T6P in the leaves may increase metabolic activity, and increase tissue resistance to abiotic stress.


Trends in the incidence of coronary heart disease and stroke and the prevalence of cardiovascular risk factors among Japanese men from 1963 to 1994.
To determine trends in the incidence of cardiovascular disease in Japan, we examined observational data on coronary heart disease, stroke, and cardiovascular risk factors among urban Japanese working men. The surveyed population included all male employees aged 40 to 59 years who worked for eight industrial companies in Osaka, the second largest metropolitan city in Japan. Surveillance for cardiovascular disease and risk factors was conducted from 1963 to 1994. The age-adjusted incidence of coronary heart disease increased from 0.4 per 1000 person-years during 1963 to 1970, to 1.5 per 1000 person-years during 1979 to 1986, and then plateaued until 1987 to 1994 (P for trend = 0.002), whereas the incidence of stroke declined from 1.2 per 1,000 person-years during 1971 to 1978, to 0.6 per 1,000 person-years in 1987 to 1994 (P for trend = 0.02). The age-adjusted mean (+/- SD) total cholesterol level, which was 4.87 +/- 2.88 mmol/L during 1963 to 1966, increased to 5.11 +/- 0.62 mmol/L during 1982 to 1983 (P <0.001), and 5.09 +/- 0.75 mmol/L during 1990 to 1991. Both mean systolic and diastolic blood pressures increased by 1 mm Hg between the periods of 1966 to 1967 and 1982 to 1983, and declined below the 1966 to 1967 levels during 1990 to 1991. The prevalence of smoking declined from 72% during 1975 to 1976, to 58% during 1990 to 1991 (P for trend <0.001). Although these findings were limited to urban middle-aged men, the increase in serum cholesterol is likely to attenuate the reduction in future rates of coronary heart disease in Japan that would have been expected to result from the declining prevalence of smoking.


Cadmium absorption and translocation of amaranth (Amaranthus mangostanus L.) affected by iron deficiency.
Amaranth (Amaranthus mangostanus L.) has superior capability for accumulating cadmium (Cd) and has the potential to be used for phytoremediation of Cd contaminated soils. Iron (Fe) is chemically similar to Cd and may mediate Cd-induced physiological or metabolic impacts in plants. The purpose was to investigate the model of time-dependent and concentration-dependent kinetics of Cd absorption under Fe deficiency, understanding the physiological mechanism of Cd absorption in amaranth roots. The kinetic characteristics of Cd uptake by amaranth grown in Cd enriched nutritional solution with or without Fe addition and with methanol-chloroform, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), and lanthanum chloride (LaCl3) were compared using 109Cd2+ isotope labeling technique. The results showed that Cd uptake was time-dependent and about 90-93% of uptake occurred during the first 150 min. The kinetics of Cd uptake showed that two stages were involved. The saturation stage fitted the Michaelis-Menten model when concentrations of Cd were lower than 12.71 μmol/L and then the absorption of Cd by roots was increased linearly during the second stage. Only linear absorption was observed with methanol-chloroform treatment while the metabolic inhibitor CCCP inhibited only the saturation absorption process, and the Ca channel inhibitor LaCl3 partially inhibited the two stages of absorption. These results indicated that the root absorption of 109Cd2+ was enhanced under Fe deficiency which induced more Fe transporters in the root cell membrane, and the Ca channel, apoplastic and symplastic pathways enhanced the Cd absorption in roots.


The Effect of Adding Honey to Zinc in the Treatment of Diarrhea in Children.
Honey has been used in medicine since ancient times. Limited reports are available to indicate its antibacterial, antiviral, and antidiarrheal properties. This study aimed to determine the effect of honey on acute diarrhea in children. This randomized clinical trial included 80 children with acute diarrhea. Forty children received honey and zinc gluconate (trial group) and 40 received only zinc gluconate (control group). After treatment, vomiting/diarrhea duration, the recovery time, and the duration of hospitalization were compared between the groups. Among the 40 children in the trial group, 19 were male and 21 were female. In the control group, 25 children were male and 15 female (P=0.26). After initiating treatment, the duration of diarrhea, recovery time, and the duration of hospitalization was significantly shorter in the trial group than in the control group (P<0.05). This study showed that honey with zinc gluconate reduces the duration of diarrhea, accelerates the recovery time, and shortens the duration of hospitalization.


Risk of psychiatric diagnoses in children and adolescents of parents with torture trauma and war trauma.
Evidence point to intergenerational effects of trauma in refugee populations. This study estimates the risk of psychiatric diagnoses in children of severely traumatized refugees. The unique clinical sample consisted of refugee parents treated for torture trauma and war trauma, and outcomes were investigated using population-level data. A nationwide register study, following all children residing in Denmark. The exposure was parental torture trauma and war trauma, and outcomes were any psychiatric disorder, mood, neurotic, behavioural and emotional disorders and disorders of psychological development. Children's hazard of being diagnosed was estimated using Cox proportional hazards regression. Study participants were followed from the date of birth or immigration to their 18th birthday. The cohort included 3 346 993 children of which 19 294 were identified as offspring to traumatized refugees. During the study period, 205 610 children were diagnosed with a psychiatric disorder. Children with parents from the Middle East and Northern Africa had a hazard ratio of 0.78 (95% CI: 0.72, 0.84) for those treated for parental trauma and 0.79 (95% CI: 0.76, 0.81) for those not treated compared with children of non-traumatized Danish-born parents. For children of parents from former Yugoslavia, the corresponding estimates were 0.69 (95% CI: 0.58, 0.81) and 0.69 (95% CI: 0.65, 0.73). The results suggest that children of parents with and without registered torture trauma and war trauma have a lower risk of being diagnosed with a psychiatric disorder compared to children of Danish-born parents. These findings contradict research done on the transmission of trauma but supports evidence suggesting mental health services underutilization by refugee and ethnic minority populations.


Protection from angiotensin II-induced cardiac hypertrophy and fibrosis by systemic lentiviral delivery of ACE2 in rats.
Angiotensin converting enzyme 2 (ACE2), a newly discovered member of the renin-angiotensin system (RAS), is a potential therapeutic target for the control of cardiovascular disease owing to its key role in the formation of vasoprotective peptides from angiotensin II. The aim of the present study was to evaluate whether overexpression of ACE2 could protect the heart from angiotensin II-induced hypertrophy and fibrosis. Lentiviral vector encoding mouse ACE2 (lenti-mACE2) or GFP was injected intracardially in 5-day-old Sprague-Dawley rats. This resulted in expression of mACE2 in cardiac tissue for the duration of the study. Infusion of 200 ng kg-1 min-1 angiotensin II for 4 weeks resulted in an 80 mmHg increase in systolic blood pressure, a significant increase in the heart weight to body weight ratio (HW:BW), and marked myocardial fibrosis in control rats. Transduction with lenti-mACE2 resulted in significant attenuation of the increased HW:BW and myocardial fibrosis induced by angiotensin II infusion. These observations demonstrate that ACE2 overexpression results in protective effects on angiotensin II-induced cardiac hypertrophy and fibrosis.


Distribution of microsatellites in relation to coding sequences within the Arabidopsis thaliana genome.
The distribution of repetitive sequences, or microsatellites, formed by either one or two base pairs and longer than eight units, has been studied in almost 1 Mb of the sequenced Arabidopsis thaliana genome. Except for those formed by only G and C residues, the repetitions are more abundant in the Arabidopsis genome than can be calculated from its nucleotide composition. They are distributed in proportions higher than expected in introns, and in the intergenic regions both proximal and distal to the coding sequences. In exons, only the TC/GA microsatellite seems to be particularly abundant. The AT/TA microsatellites produce more length variation between Arabidopsis ecotypes than the A/T repeated sequences. These two classes are more abundant per kilobase than coding sequences in the Arabidopsis genome. The results indicate not only that the presence of microsatellites is not an effect of random distribution of nucleotides, but that their resolution as molecular markers may be equivalent to the number of genes and also that they do not seem to be systematically linked to specific regulatory sequences proximal to genes.


Patient tailored resection planning in patients undergoing liver surgery for colorectal liver metastases; how and why should you do it?
A systematic preoperative evaluation to determine the individual resection strategy in patients with colorectal liver metastases (CRLM) was assessed as to its clinical value. From 2009 to 2011, 75 patients with CRLM who were scheduled for surgery were prospectively included and received an additional preoperative systematic evaluation in the presence of a hepatobiliary radiologist and the hepatobiliary surgeon scheduled to perform the surgery. The following items were assessed in a standardized manner: lesion detection and characterization, presence of extrahepatic disease, vascular anatomy, and resection strategy. Intraoperative findings and histopathological results were prospectively recorded. Five out of 75 patients were not considered to be eligible for surgery due to additional findings, such as additional metastases or extrahepatic disease. Sensitivity and specificity for detection of individual CRLM were 80.9% (95% CI 75.7-86.1%) and 69.1% (95% CI 59.1-79.1%), respectively. Radical resections were performed in 87.1%. There was one futile laparotomy (1.4%). In patients with colorectal liver metastases, standardized preoperative work-up, with subsequent planning of an individualized resection in a jointed meeting of a hepatobiliary radiologist and the surgeon who will perform the operation, leads to a high level of radical resections and a low number of futile laparotomies.


Glycolipid storage material in Fabry's disease: a study by electron microscopy, freeze-fracture, and digital image analysis.
The glycolipid storage material in Fabry's disease was studied by electron microscopy of thin-sectioned (TS) and freeze-fractured (FF) specimens. In the kidney all deposits were found to be located in lysosomes, arranged as lamellar stacks. Deposits in the heart consisted of intracytoplasmic concentric whirls or folded lamellar structures. High resolution TS micrographs disclosed various defects in the lamellar structure. For stabilization, such defects require additional amphiphilic, surface-active molecules. These molecules could interact with other cellular constituents. The lamellar periodicity of the deposits in FF specimens was determined by reconstruction of the three-dimensional fracture face by digital image analysis. Homogeneous multilamellar deposits exhibited a periodicity of 14-15 nm, contrasting with the conventional estimates of 4-5 nm on TS micrographs. This difference is explained by better preservation of the physiologic hydrated state in FF specimens, with 1 vol of lipids binding 2 vol of water. Inhomogeneous structures with an even higher state of hydration included water lenses between the sheets. The strong hydration obviously contributes to the enlargement of the intracellular glycolipid deposits.


Rhodotorula rubra ventriculitis.
We describe a case of post-operative ventriculitis in an immunocompetent patient caused by an unusual organism, namely Rhodotorula rubra. The patient was treated successfully with antifungal agents.


Comparison of taurine biosynthesis ability between juveniles of Japanese flounder and common carp.
This study was conducted to investigate taurine deficiency and the ability of taurine biosynthesis in both juvenile Japanese flounder (JF) and juvenile common carp (CC) in vivo using low taurine level diets. Three different taurine level diets were prepared by the supplementation of taurine to the basal composition (JF--0, 0.5 and 1.5% in JF; CC--0, 1, 3% in CC). The final average body weight and feed efficiency of JF fed the JF - 1.5% was significantly higher than those of fish fed on the JF--0%. On the other hand, no significant difference was observed in CC fed with CC--0, 1, and 3% diets. The taurine retention rate was negative in the case of JF-fed with the taurine-free supplement (JF--0%). On the other hand, the taurine retention rate was about 280% in the case of CC-fed with the taurine-free supplement (CC--0%). These findings indicate that while taurine is essential for growth of JF, it is not essential for the growth of CC.


Weak and vanishing upper mantle discontinuities generated by large-scale lithospheric delamination in the Longmenshan area, China.
A large amount of high-quality teleseismic data is used for common conversion point (CCP) stacking of receiver functions in the Longmenshan area and near-by region. The results show that a large-scale high-velocity anomaly (LHVA) or lithospheric delamination can modify the structure of upper mantle discontinuities or weaken the phase boundary of olivine, which is a very important finding and can be used to assess stagnant slabs in the mantle transition zone globally. The deepening region of the 660 km discontinuity beneath the Songpan-Ganzi terrane identified in this study might be generated by the LHVA.


A long-lasting porcine model of ARDS caused by pneumonia and ventilator-induced lung injury.
Animal models of acute respiratory distress syndrome (ARDS) do not completely resemble human ARDS, struggling translational research. We aimed to characterize a porcine model of ARDS induced by pneumonia-the most common risk factor in humans-and analyze the additional effect of ventilator-induced lung injury (VILI). Bronchoscopy-guided instillation of a multidrug-resistant Pseudomonas aeruginosa strain was performed in ten healthy pigs. In six animals (pneumonia-with-VILI group), pulmonary damage was further increased by VILI applied 3 h before instillation and until ARDS was diagnosed by PaO2/FiO2 < 150 mmHg. Four animals (pneumonia-without-VILI group) were protectively ventilated 3 h before inoculum and thereafter. Gas exchange, respiratory mechanics, hemodynamics, microbiological studies and inflammatory markers were analyzed during the 96-h experiment. During necropsy, lobar samples were also analyzed. All animals from pneumonia-with-VILI group reached Berlin criteria for ARDS diagnosis until the end of experiment. The mean duration under ARDS diagnosis was 46.8 ± 7.7 h; the lowest PaO2/FiO2 was 83 ± 5.45 mmHg. The group of pigs that were not subjected to VILI did not meet ARDS criteria, even when presenting with bilateral pneumonia. Animals developing ARDS presented hemodynamic instability as well as severe hypercapnia despite high-minute ventilation. Unlike the pneumonia-without-VILI group, the ARDS animals presented lower static compliance (p = 0.011) and increased pulmonary permeability (p = 0.013). The highest burden of P. aeruginosa was found at pneumonia diagnosis in all animals, as well as a high inflammatory response shown by a release of interleukin (IL)-6 and IL-8. At histological examination, only animals comprising the pneumonia-with-VILI group presented signs consistent with diffuse alveolar damage. In conclusion, we established an accurate pulmonary sepsis-induced ARDS model.


Raman imaging as a new approach to identification of the mayenite group minerals.
The mayenite group includes minerals with common formula Ca12Al14O32-x(OH)3x[W6-3x], where W = F, Cl, OH, H2O and x = 0-2. This distinction in the composition is associated with W site which may remain unoccupied or be occupied by negatively charged ions: OH-, F-, Cl-, as well as neutral molecules like H2O. However, there is no experimental approach to easily detect or differentiate mineral species within the mayenite group. Electron micro-beam facilities with energy- or wavelength-dispersive X-ray detectors, as most common tools in mineralogy, appear to be insufficient and do not provide a definite identification, especially, of hydroxylated or hydrated phases. Some solution provides typical Raman analysis ensuring identification of minerals and 3D Raman imaging as an innovative approach to distinguish various co-existing minerals of the mayenite group within a small area of the rock sample. Raman spectroscopy has also been successfully used for a determination of water type incorporated into the mineral structure as well as for a spatial distribution of phases by cluster approach analysis and/or integrated intensity analysis of bands in the hydroxyl region. In this study, Raman technique was for the first time used to reconstruct a 3D model of mayenite group mineral zonation, as well as to determine a way of water incorporation in the structure of these minerals. Moreover, for the first time, Raman data were correlated with alterations during the mineral-forming processes and used for reconstruction of the thermal history of studied rock. As a result, the influence of combustion gases has been proposed as a crucial factor responsible for the transformation between fluormayenite and fluorkyuygenite.


Systemic absorption of oral vancomycin in patients with renal insufficiency and antibiotic-associated colitis.
The systemic absorption of orally administered vancomycin was evaluated in five patients (six occasions) with moderate to severe renal insufficiency and documented antibiotic-associated colitis. The patients' ages ranged from 28 to 63 years and weights varied from 50.0 to 76.2 kg. Vancomycin doses were 125 mg (one case), 250 mg (three cases), and 500 mg (two cases) every six hours. Multiple serum concentrations were obtained (range four to 19) during the seven- to 28-day courses of vancomycin therapy. Vancomycin serum concentrations were detectable in five of the six cases as soon as two hours after the first dose, and plateaued within four days. A linear relationship between daily dose and the vancomycin serum concentration was observed (r = .8575, P less than .01). Routine monitoring of vancomycin serum concentrations in adult patients may not be necessary unless high dose (greater than 2 g/d) or prolonged therapy (greater than ten days) is required.


Beta-Arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic beta cells.
Glucagon-like peptide-1 (GLP-1) is a polypeptide hormone secreted from enteroendocrine L cells and potentiates glucose-dependent insulin secretion in pancreatic beta cells. Recently the GLP-1 receptor (GLP-1 R) has been a focus for new anti-diabetic therapy with the introduction of GLP-1 analogues and DPP-IV inhibitors, and this has stimulated additional interest in the mechanisms of GLP-1 signaling. Here we identify a mechanism for GLP-1 action, showing that the scaffold protein beta-arrestin-1 mediates the effects of GLP-1 to stimulate cAMP production and insulin secretion in beta cells. Using a coimmunoprecipitation technique, we also found a physical association between the GLP-1 R and beta-arrestin-1 in cultured INS-1 pancreatic beta cells. beta-Arrestin-1 knockdown broadly attenuated GLP-1 signaling, causing decreased ERK and CREB activation and IRS-2 expression as well as reduced cAMP levels and impaired insulin secretion. However, beta-arrestin-1 knockdown did not affect GLP-1 R surface expression and ligand-induced GLP-1 R internalization/desensitization. Taken together, these studies indicate that beta-arrestin-1 plays a role in GLP-1 signaling leading to insulin secretion, defining a previously undescribed mechanism for GLP-1 action.


Steroid secretion by the prepubertal human testis.
It has been demonstrated that the human testis secretes testosterone and, to a smaller extent and less constantly, also androstenedione. Testosterone, progesterone, 17 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone have been measured in the spermatic and peripheral venous blood of prepubertal boys undergoing surgery for undescended testis or inguinal hernia repair. The spermatic plasma levels of testosterone and progesterone were significantly higher than peripheral levels. A significant spermatic-peripheral gradient was not found for 17 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone. These studies demonstrate that the secretory pattern of the human prepubertal testis is different from that of the adults.


TiO2 nanoparticles aggregation and disaggregation in presence of alginate and Suwannee River humic acids. pH and concentration effects on nanoparticle stability.
The behavior of manufactured TiO2 nanoparticles is studied in a systematic way in presence of alginate and Suwannee River humic acids at variable concentrations. TiO2 nanoparticles aggregation, disaggregation and stabilization are investigated using dynamic light scattering and electrophoretic experiments allowing the measurement of z-average hydrodynamic diameters and zeta potential values. Stability of the TiO2 nanoparticles is discussed by considering three pH-dependent electrostatic scenarios. In the first scenario, when pH is below the TiO2 nanoparticle point of zero charge, nanoparticles exhibit a positively charged surface whereas alginate and Suwannee River humic acids are negatively charged. Fast adsorption at the TiO2 nanoparticles occurs, promotes surface charge neutralization and aggregation. By increasing further alginate and Suwannee River humic acids concentrations charge inversion and stabilization of TiO2 nanoparticles are obtained. In the second electrostatic scenario, at the surface charge neutralization pH, TiO2 nanoparticles are rapidly forming aggregates. Adsorption of alginate and Suwannee River humic acids on aggregates leads to their partial fragmentation. In the third electrostatic scenario, when nanoparticles, alginate and Suwannee River humic acids are negatively charged, only a small amount of Suwannee River humic acids is adsorbed on TiO2 nanoparticles surface. It is found that the fate and behavior of individual and aggregated TiO2 nanoparticles in presence of environmental compounds are mainly driven by the complex interplay between electrostatic attractive and repulsive interactions, steric and van der Waals interactions, as well as concentration ratio. Results also suggest that environmental aquatic concentration ranges of humic acids and biopolymers largely modify the stability of aggregated or dispersed TiO2 nanoparticles.


Retinoic acid-induced testosterone production and retinoylation reaction are concomitant and exhibit a positive correlation in Leydig (TM-3) cells.
Retinoic acid (RA) exerts diverse biological effects in the control of cell growth in embryogenesis and oncogenesis. The effects of RA are thought to be mediated by the nuclear retinoid receptors; however, not all the effects of RA can be explained by the nuclear receptor pathways. Indeed, retinoylation is another mechanism of action elicited by RA. In growing TM-3 Leydig cell cultures, the extent of retinoylation depends in a saturable manner on the initial concentration of 3H-RA, time and cell number. In addition, dose-response curves for RA-induced testosterone production and retinoylation are concomitant and exhibit a positive correlation. In the present study we demonstrate that RA is able to influence a retinoylation reaction on protein(s) probably involved on steroidogenesis.


Building high affinity human antibodies by altering the glycosylation on the light chain variable region in N-acetylglucosamine-supplemented hybridoma cultures.
We attempted to improve antibody affinity by varying glycosylation on the light chain variable region. The human hybridoma line HB4C5 produces an antibody reactive to lung adenocarcinoma, which possess a N-glycosylated carbohydrate chain on the light chain hypervariable region. It has been shown that altering this carbohydrate structure can be accomplished by varying the level of N-acetylglucosamine in glucose free medium, a change in the carbohydrate chain could be induced which resulted in modifying antigen binding. By culturing the cells in media containing more than 20 mM N-acetylglucosamine, cells produced antibody with 10 fold improved affinity as compared with antibody produced in 20 mM glucose-containing medium. A newly induced light chain glycoform produced in the N-acetylglucosamine-containing medium was shown to be responsible for this antigen binding enhancement. Addition of glucose in the N-acetylglucosamine-containing media led to decreased antibody affinity and slightly inhibited production of a new light chain in a dose-dependent manner. Combination of 20 mM N-acetylglucosamine and 0.5 mM glucose gave a higher antibody production without the decrease of the antigen binding. These results indicate that optimization of N-glycosylation on the light chain, which leads to higher antigen binding, can be accomplished by adjusting a ratio of glucose and N-acetylglucosamine in the culture medium.


Plant growth-promoting rhizobacteria are important contributors to rice yield in karst soils.
The difficulty of releasing nutrients from soils in karst areas limits the yield of local crops and leads to poverty. In this study, two strains of plant growth-promoting rhizobacteria (PGPR) were isolated from the rhizosphere soil of typical plants in karst areas, which were both identified as Bacillus sp. and named GS1 and N1. And two isolates were used to construct a composite PGPR named MC1. These three strains of PGPR were used for soil inoculation in the pot experiment and field trial and their capacity to promote rice development was assessed. The results showed that MC1 inoculation exhibited notable rice growth-promoting ability in pot experiments, and, respectively, had an increment of 16.96, 18.74, and 11.50% in shoot biomass, total biomass, and rice height compared with control. This is largely attributed to PGPR's capacity to secrete phytohormones and soil enzymes, particularly urease (UE) in GS1, whose secreted UE content was significantly higher by 12.18% compared to the control. When applied to the field, MC1 inoculation not only increased rice yield by 8.52% and the available nutrient content in rice rhizosphere soil, such as available phosphorus (AP) and exchangeable magnesium (EMg); but also improved the abundance of beneficial rhizobacteria and the diversity of microbial communities in rice rhizosphere soil. Results in this study revealed that inoculated PGPR played a major role in promoting rice growth and development, and a new strategy for facilitating the growth of rice crops in agriculture was elucidated. The online version contains supplementary material available at 10.1007/s13205-023-03593-0.


[Compensation for occupational diseases after tomodensitometry screening for benign pleuro-pulmonary disease in a multiregional post-occupational medical surveillance program of asbestos-exposed retired workers].
Underreporting of occupational diseases related to asbestos exposure remains a matter of concern in France. The aim of this study was to evaluate the number of claims for compensation for asbestos-related non-malignant pulmonary or pleural occupational disease in subjects having undergone a chest CT-scan in a multiregional screening programme. Among the 5444 voluntary retired asbestos-exposed subjects recruited in four regions between 2003 and 2005 who had undergone a chest CT-scan, the number of claims for compensation for an asbestos-related pulmonary or pleural benign disease was analysed in 2006 and 2010. Following CT-scan screening, 17.2% of participants were acknowledged as presenting with an asbestos-related non-malignant occupational disease, essentially pleural plaques, by the French National Health Insurance fund. Underreporting decreased as duration of follow-up after CT-scan increased. Nevertheless, 4 years after CT-scan, underreporting was still as high as 36% for subjects identified as presenting with pleural plaques. Mean duration between the date of CT-scan and the date of recognition as occupational disease was 7.4 months, shorter in cases where screening was coordinated by specialized centres. A plan of action for an easier claiming process for compensation of asbestos-related diseases is desired. This could probably be obtained through improved sensitization of physicians engaged in the follow-up of asbestos-exposed subjects, and by standardization of the interpretation and reporting of asbestos-related abnormalities observed on chest CT-scans.


A Practical Approach to Refractory and Recurrent Barrett's Esophagus.
Endoscopic eradication therapy (EET) is recommended for patients with Barrett's esophagus (BE)-associated neoplasia and is effective in achieving complete eradication of intestinal metaplasia (CE-IM). However, BE that is refractory to EET, defined as partial or no improvement in dysplasia after less than or equal to 3 ablative sessions, and the development of recurrence post-EET is not uncommon. Identification of refractory BE or recurrent intestinal metaplasia should prompt esophageal physiologic testing and modification of antireflux strategy, as appropriate. In patients who ultimately fail standard EET despite optimization of reflux control, salvage EET with alternate modalities may need to be considered.


Glyoxalase I "null" allele in a new family: identification by abnormal segregation pattern and quantitative assay.
A GLO-I "null" allele in a family was indicated by an abnormal segregation pattern and by half normal red cell enzyme activity in carriers. This is the third reported instance of this uncommon allele, and the first with confirmation by quantitation of enzyme activity.


Small regions of overlapping deletions on 6q26 in human astrocytic tumours identified using chromosome 6 tile path array-CGH.
Deletions of chromosome 6 are a common abnormality in diverse human malignancies including astrocytic tumours, suggesting the presence of tumour suppressor genes (TSG). In order to help identify candidate TSGs, we have constructed a chromosome 6 tile path microarray. The array contains 1,780 clones (778 P1-derived artificial chromosome and 1,002 bacterial artificial chromosome) that cover 98.3% of the published chromosome 6 sequences. A total of 104 adult astrocytic tumours (10 diffuse astrocytomas, 30 anaplastic astrocytomas (AA), 64 glioblastomas (GB)) were analysed using this array. Single copy number change was successfully detected and the result was in general concordant with a microsatellite analysis. The pattern of copy number change was complex with multiple interstitial deletions/gains. However, a predominance of telomeric 6q deletions was seen. Two small common and overlapping regions of deletion at 6q26 were identified. One was 1,002 kb in size and contained PACRG and QKI, while the second was 199 kb and harbours a single gene, ARID1B. The data show that the chromosome 6 tile path array is useful in mapping copy number changes with high resolution and accuracy. We confirmed the high frequency of chromosome 6 deletions in AA and GB, and identified two novel commonly deleted regions that may harbour TSGs.


Characteristics and outcome of primary Budd-Chiari syndrome due to Behçet's syndrome.
Behçet's syndrome (BS) is a known cause of Budd-Chiari syndrome (BCS). We aimed at identifying the prevalence of BS in patients with BCS, analyzing different clinical presentations, treatment modalities and outcome of these patients. We conducted a retrospective cohort study, in which all medical records of patients who were presented to Tropical Medicine Department, Ain Shams University with a confirmed diagnosis of primary BCS from May 2005 to December 2016 were collected and analyzed. In total, 271 patients had a confirmed diagnosis of primary BCS, included Group I: 232 (85.6%) patients with BCS without BS and Group II: 39 patients (14.4%) with BCS due to BS. Male gender (P=0.000), oral ulcers, genital ulcers, Prominent abdominal veins, lower limb swellings, lower extremity deep venous thrombosis (P=0.000) and jaundice (P=0.003) were more frequent in group II patients. The presence of intrahepatic collaterals (P=0.004) and IVC thrombosis (P=0.000) was significant in group II. Medical treatment alone in the form of immunosuppressive drugs and anticoagulation (66.7% vs. 24.1%)±IVC stenting (23% vs. 1.3%) (P=0.000) were the main treatment modalities for BCS related to BS. The frequency of HCC in BS was significantly higher (10.26% vs. 2.59%) (P=0.013). The prevalence of BS in Egyptian patients with BCS is considerably high. The clinical presentation of these patients was different from those without BS. Besides, the incidence of HCC was higher in patients with BS, whereas the mortality did not differ between the two groups.


Synthetic library design.
Compound libraries have an important role in the drug discovery process. Various computational methods are available as decision support tools for medicinal chemists involved in compound library synthesis programs. These methods can be used to assemble a flexible library design scheme consisting of a structure-based library design followed by property-biased library refinement and final selection according to structure-activity-relationship considerations.


Crystal structure of the native plasminogen reveals an activation-resistant compact conformation.
Plasminogen is the zymogen form of plasmin and the precursor of angiostatin. It has been implicated in a variety of disease states, including thrombosis, bleeding and cancers. The native plasminogen, known as Glu-plasminogen, contains seven domains comprising the N-terminal peptide domain (NTP), five kringle domains (K1-K5) and the C-terminal serine protease domain (SP). Previous studies have established that the lysine binding site (LBS) of the conserved kringle domains plays a crucial role in mediating the regulation of plasminogen function. However, details of the related conformational mechanism are unknown. We aim to understand in more detail the conformational mechanism of plasminogen activation involving the kringles. We crystallized the native plasminogen under physiologically relevant conditions and determined the structure at 3.5 Å resolution. We performed structural analyses and related these to the literature data to gain critical understanding of the plasminogen activation. The structure reveals the precise architecture of the quaternary complex. It shows that the Glu-plasminogen renders its compact form as an activation-resistant conformation for the proteolytic activation. The LBSs of all kringles, except K1, are engaged in intra-molecular interactions while only K1-LBS is readily available for ligand binding or receptor anchorage. The structure also provides insights into the interactions between plasminogen and α2-antiplasmin, the primary physiological inhibitor of plasmin. Furthermore, the data presented explain why a conformational transition to the open form is necessary for plasminogen activation as well as angiostatin generation, and provide a rationale for the functional hierarchy of the different kringles.


Development of the nervous and cardiovascular systems in low-birth-weight infants fed a taurine-supplemented formula.
An adapted cow's milk formula with or without supplemental taurine (480 mumol/l) was fed for 16 weeks to 20 low-birth-weight infants. In the 2nd and 16th weeks of life, respectively, the following parameters were determined: growth, sonography of heart and brain, ECG, EEG, neurological development and the taurine concentration of plasma and urine. None of the parameters investigated was influenced by taurine supplementation except the urinary taurine excretion. At least according to these data, the addition of taurine to whey-predominant infant formulae seems to be unnecessary for the development of heart and brain function in low-birth-weight infants.


Novel bovine heart calmodulin-dependent protein kinase which phosphorylates a high molecular weight calmodulin-binding protein.
A novel calmodulin-dependent protein kinase has been isolated from bovine cardiac muscle by successive chromatography on DEAE-Sepharose 6B, Calmodulin-Sepharose 4B affinity and Sepharose 6B chromatography columns. The protein kinase was shown by gel filtration chromatography to have a molecular mass of 36,000 daltons. The highly purified protein kinase stoichiometrically phosphorylated the high molecular weight calmodulin-binding protein from cardiac muscle [Sharma RK (1990) J Biol Chem 265, 1152-1157] in a Ca2+/calmodulin-dependent manner. The phosphorylation resulted in the maximal incorporation of 1 mol of phosphate/mol of the high molecular weight calmodulin-binding protein. Other Ca2+/calmodulin-dependent protein kinases failed to phosphorylate the high molecular weight calmodulin-binding protein. The distinct substrate specificity of this protein kinase indicates that it is not related to the known calmodulin-dependent protein kinases and therefore constitutes a novel protein kinase.


[Skin impedance and phoreographic index in psoriasis. Relationship with action kinetics of three treatments].
In a previous study, impedance measurements and phoreographic response were shown to quantify significant differences between involved and non-involved skin in psoriasis. The same techniques were used to objectivate the evolution on skin condition on patients treated with dioxyanthranol, difluprednate, and photochemotherapy associated with 8-methoxypsoralen. Each of these treatments was applied to four subjects. On patients treated with dioxyanthranol or difluprednate, impedance and phoreographic response return to "normal" values within 5--10 days and 1--2 days, respectively. It takes a longer time with photochemotherapy, and it is noteworthy that the treatment also alters the phoreographic response of non-involved skin. The changes observed in electrophysiological parameters are discussed in relation with recent ideas on pharmacology of antipsoriatic treatments and on dynamic properties of biological membranes. The results are in good correlation with clinical data and exemplify the usefulness of these methods in following the treatment kinetics.


Biological reaction to polyethylene particles in a murine calvarial model is highly influenced by age.
Particle-induced osteolysis is driven by multiple factors including bone metabolism, inflammation, and age. The objective of this study was to determine the influence of age on polyethylene (PE) particle-induced osteolysis in a murine calvarial model comparing 2-month-old (young) versus 24-month-old (old) mice. After PE particle implantation, calvaria were assessed at days (D) 3, D7, D14, and D21 via chemoluminescent imaging for inflammation (L-012 probe). In addition micro-computed tomography (micro-CT) and histomorphometry end points addressed the bone reaction. Inflammation peaked at D7 in young mice and D14 in old mice. Using micro-CT, a nadir of mature bone was recorded at D7 for young mice, versus D21 for old mice. Besides, regenerating bone peaked at distinct timepoints: D7 for young mice versus D21 for old mice. In the young mice group, the histomorphometric findings correlated with micro-CT regenerating bone findings at D7, associated with ample osteoïd deposition. No osteoïd could be histologically quantified in the old mice group at D7. This study demonstrated that the biological reaction to polyethylene particles is highly influenced by age.


Adverse Events Among Hospitalized Critically Ill Patients: A Retrospective Cohort Study.
The objective of this study was to estimate the frequency and type of adverse events (AEs) among critically ill patients and identify patient and hospital factors associated with AEs and clinical and health care utilization consequences of AEs. This retrospective cohort study includes patients admitted to 30 intensive care units (ICUs) in Alberta, Canada from May 2014 to April 2017. The main outcome was AEs derived from validated ICD-10, Canadian code algorithms for 18 AEs. Estimates of the proportion and rate of AEs are presented. The association between documented AEs and patient (eg, age, sex, comorbidities) and hospital (eg, ICU site and type, length of stay, readmission) variables are described using regression methods. Of 49,447 hospital admissions with admission to ICU, ≥1 AEs were documented in 12,549 (25%) admissions. The most common AEs were respiratory complications (10%) and hospital-acquired infections (9%). AEs were associated with having ≥2 comorbidities [odds ratio (OR)=1.4, 95% confidence interval (CI)=1.3-1.4], being admitted to the ICU from the operating room or another hospital ward (OR=1.8, 95% CI=1.7-2.0 and OR=2.7, 95% CI=2.5-3.0, respectively) and being readmitted to ICU during their hospital stay (OR=4.8, 95% CI=4.7-5.6). Patients with an AE stayed 5.4 days longer in ICU (95% CI=5.2-5.6 d, P<0.001), 18.2 days longer in hospital (95% CI=17.7-18.8 d, P<0.001) and had increased odds of hospital mortality (OR=1.5, 95% CI=1.4-1.6) than those without an AE. AEs are common among critically ill patients and certain factors are associated with AEs. Documented AEs are associated with longer stays and increased mortality.


Oncology and Primary Care Provider Views on Cancer Survivorship Care: Mind the Gap.
Coordination between oncology and primary care practices in cancer survivorship is lacking. To identify cancer care coordination perceptions, knowledge, and practices in a sample of Oklahoma oncology care providers (ONCs) and primary care providers (PCPs) regarding post-treatment care of adult cancer survivors. Cross-sectional, statewide survey by mail/web link in 2014/5. PCPs identified through a primary care research network, primary care organization membership lists; ONCs identified through www.Healthgrades.com. Contacts who were clinically active and seeing cancer patients were eligible. The final sample size included 101 ONCs and 58 PCPs who reported actively seeing cancer patients. Responses to predominately Likert scale or ranked-order questions derived from the Survey of Physician Attitudes Regarding the Care of Cancer Survivors. Chi square and t tests were performed to test bivariate associations between provider type and survey measures. Statistically significant differences (P < .05) between ONC and PCP perceptions were observed for several questions on communication between the 2 provider types, ONC perceptions of PCP ability to address survivorship care, and responsibilities for post-treatment care. Highly discrepant perspectives between ONCs and PCPs regarding communications and responsibilities for survivorship care may lead to adverse health outcomes. Interventions aimed at improving care coordination for cancer survivors should define each provider group's responsibilities in survivorship care, and create structures and processes that foster clear channels of communication between ONC and PCP practices.


Attentional bias in addictive behaviors: a review of its development, causes, and consequences.
A wealth of research from the past two decades shows that addictive behaviors are characterized by attentional biases for substance-related stimuli. We review the relevant evidence and present an integration of existing theoretical models to explain the development, causes, and consequences of addiction-related attentional biases. We suggest that through classical conditioning, substance-related stimuli elicit the expectancy of substance availability, and this expectancy causes both attentional bias for substance-related stimuli and subjective craving. Furthermore, attentional bias and craving have a mutual excitatory relationship such that increases in one lead to increases in the other, a process that is likely to result in substance self-administration. Cognitive avoidance strategies, impulsivity, and impaired inhibitory control appear to influence the strength of attentional biases and subjective craving. However, some measures of attentional bias, particularly the addiction Stroop, might reflect multiple underlying processes, so results need to be interpreted cautiously. We make several predictions that require testing in future research, and we discuss implications for the treatment of addictive behaviors.


Helicobacter macacae MazF interplays with Escherichia coli homologs and enhances antibiotic tolerance.
Toxin-antitoxin systems are highly variable, even among strains of the same bacterial species. The MazEF toxin-antitoxin system is found in many bacteria and plays important roles in various biological processes such as antibiotic tolerance and phage defense. However, no interplay of MazEF systems between different species was reported. MazEF toxin-antitoxin system of Helicobacter macacae was examined in three Escherichia coli strains with and without endogenous MazEF knockout. In vivo toxicity, antibiotic tolerance, and live/dead staining followed by flowcytometry analysis were performed to evaluate the functionality and interplay of the toxin-antitoxin system between the two species. Controlled ectopic expression of MazF of H. macacae (MazFhm) in E. coli did not affect its growth. However, in endogenous MazEF knockout E. coli strains, MazFhm expression caused a sharp growth arrest. The toxicity of MazFhm could be neutralized by both the antitoxin of MazE homolog of H.macacae and the antitoxin of MazE of E. coli, indicating interplay of MazEF toxin-antitoxin systems between the two species. Induced expression of MazFhm enhanced tolerance to a lethal dose of levofloxacin, suggesting enhanced persister formation, which was further confirmed by live/dead cell staining. The MazEF toxin-antitoxin system of H. macace enhances persister formation and thus antibiotic tolerance in E. coli. Our findings reveal an interplay between the MazEF systems of H. macacae and E. coli, emphasizing the need to consider this interaction while evaluating the toxicity and functionality of MazF homologs from different species in future studies.


Effect of montelukast on polymorphonuclear leukocyte functions in asthmatic patients.
Leukotriene receptor antagonists are being used widely in the treatment of bronchial asthma. They have been shown to possess anti-inflammatory properties, but there is no sufficient data about their effects on polymorphonuclear leukocyte functions. The aim of this study was to investigate the effects of montelukast, a specific cysteinyl leukotriene-1 receptor antagonist, on human polymorphonuclear leukocyte (PMN) functions (phagocytic and intracellular killing activity) in asthmatic patients. Fifteen mild to moderate asthmatic patients were included in the study. They were treated with montelukast (10 mg/day per os) in addition to their previous medications for 2 weeks. Whole blood samples of patients were taken before and after this treatment period. Phagocytic activities and intracellular killing activities of polymorphonuclear leukocytes isolated from whole blood samples were tested by using appropriate technics. Phagocytic and intracellular killing activities of PMNs were significantly increased (p<0.001, p<0.05) by montelukast compared to those before treatment. These results show that montelukast has an enhancing effect on PMN functions in asthmatic patients.


Influence of age on the cardiovascular response during graded haemorrhage in anaesthetized rats.
The present study was designed to follow the cardiovascular response to graded haemorrhage in two groups of adult rats of different ages. Group A (n = 10) had a mean body weight (bwt) of 655 g (50 weeks old) and group B (n = 10) had a mean bwt of 250 g (12 weeks old). After induction of anaesthesia, the carotid artery was cannulated for continuous intra-arterial blood pressure monitoring and for controlled haemorrhage. Five per cent of the total blood volume (TBV) was removed every 15 min until a maximum of 50% was reached. Mean arterial pressure (MAP) fell by 4-9 mm Hg each time 5% TBV was removed in both groups, and at the end of the study the MAP was comparable in the two groups (34 +/- 10 mm Hg in group A and 28 +/- 8 mm Hg in group B). There were no significant changes in heart rate (HR) in the young animals during haemorrhage, while there was a significant drop in heart rate in the older animals when blood loss exceeded 15% of TBV (P < 0.05). A significant difference was also observed in HR between the two groups of animals with blood loss in excess of 20% TBV (P < 0.05). It was concluded that although the hypotension induced by graded haemorrhage was similar in young and old rats, the older animals were less able to maintain their HR, probably as a consequence of age- and anaesthetic-related changes in sympathetic activity.


Implant Angulation Effect on the Fracture Resistance of Monolithic Zirconia Custom Abutments: An In Vitro Study.
To investigate the fracture resistance and performance of zirconia when employed for the fabrication of implant abutments with different angulations, simulating anterior maxillary oral rehabilitation. Forty-five monolithic zirconia custom abutments of internal conical implant connection were CAD/CAM designed and fabricated. The specimens were divided into three groups (n = 15/group) according to implant-to-abutment angulation. The angulations used were; 0°, 15°, and 25°. The abutments were loaded until failure at 135° using the Universal Testing Machine (Instron, Canton, MA). Collected data were statistically analyzed using one-way ANOVA and post hoc Tukey test. Mean (±standard deviation) load at fracture of the zirconia abutments for the three groups were 962.37 ± 93.81 N (Gr15) > 718.25 ± 93.71 N (Gr25) > 534.05 ±133.77 N (Gr0). Statistically significant difference (p < 0.0001) was found between all groups; Gr0 vs. Gr15, Gr0 vs. Gr25, Gr15 vs. Gr25. Contrary to expectations, the non-angulated monolithic zirconia abutments presented the lowest fracture resistance values. Angulating the abutments 15 or 25 degrees, following the palatal resorption pattern of the premaxilla, significantly increased the in vitro fracture resistance.


Magnetic resonance imaging surveillance following vestibular schwannoma resection.
To describe the incidence, pattern, and course of postoperative enhancement within the operative bed using serial gadolinium-enhanced magnetic resonance imaging (MRI) following vestibular schwannoma (VS) resection and to identify clinical and radiologic variables associated with recurrence. Retrospective cohort study. All patients who underwent microsurgical resection of VS between January 2000 and January 2010 at a single tertiary referral center were reviewed. Postoperative enhancement patterns were characterized on serial MRI studies. Clinical follow-up and outcomes were recorded. During the last 10 years, 350 patients underwent microsurgical VS resection, and of these, 203 patients met study criteria (mean radiologic follow-up, 3.5 years). A total of 144 patients underwent gross total resection (GTR), 32 received near-total resection (NTR), and the remaining 27 underwent subtotal resection (STR); 98.5% of patients demonstrated enhancement within the operative bed following resection (58.5% linear, 41.5% nodular). Stable enhancement patterns were seen in 24.5% of patients, regression in 66.0%, and resolution in only 3.5% of patients on the most recent postoperative MRI. Twelve patients recurred a mean of 3.0 years following surgery. The average maximum linear diameter growth rate among recurrent tumors was 2.3 mm per year. Those receiving STR were more than nine times more likely to experience recurrence compared to those undergoing NTR or GTR (P < .001). Nodular enhancement on the initial postoperative MRI was associated with a 16-fold increased risk for future recurrence compared to those with linear patterns (P = .008). Among those with nodular enhancement on baseline postoperative MRI, a maximum linear diameter of ≥ 15 mm or volume of ≥ 0.4 cm(3) was associated with an approximate five-fold increased risk for future growth (P < .02). Persistent nonspecific radiologic enhancement within the postoperative field is common, making the diagnosis of tumor recurrence challenging. Factors including completeness of resection and baseline postoperative MRI findings provide valuable information regarding risk for recurrence, which may assist the clinician in determining an appropriate postoperative MRI surveillance schedule. Future studies using standardized terminology and consistent study metrics are needed to further refine surveillance recommendations.