Evidence for semantic learning in profound amnesia: an investigation with patient H.M.
Until recently, it seemed unlikely that any semantic knowledge could be acquired following extensive bilateral damage to the medial temporal lobes (MTL). Although recent studies have demonstrated some semantic learning in amnesic patients, questions remain regarding the limits of this capacity and the extent to which it relies on those patients' residual MTL function. The present study examined whether detailed, semantic memory could be acquired by a patient with no functioning hippocampus. We used cued recall and forced-choice recognition tasks to investigate whether the patient H.M. had acquired knowledge of people who became famous after the onset of his amnesia. Results revealed that, with first names provided as cues, he was able to recall the corresponding famous last name for 12 of 35 postoperatively famous personalities. This number nearly doubled when semantic cues were added, suggesting that his knowledge of the names was not limited to perceptual information, but was incorporated in a semantic network capable of supporting explicit recall. In forced-choice recognition, H.M. discriminated 87% of postmorbid famous names from foils. Critically, he was able to provide uniquely identifying semantic facts for one-third of these recognized names, describing John Glenn, for example, as "the first rocketeer" and Lee Harvey Oswald as a man who "assassinated the president." Although H.M.'s semantic learning was clearly impaired, the results provide robust, unambiguous evidence that some new semantic learning can be supported by structures beyond the hippocampus proper.


Constraints on the evolution of tolerance to herbicide in the common morning glory: resistance and tolerance are mutually exclusive.
Evolutionary biologists explain the maintenance of intermediate levels of defense in plant populations as being due to trade-offs, or negative genetic covariances among ecologically important traits. Attempts at detecting trade-offs as constraints on the evolution of defense have not always been successful, leading some to conclude that such trade-offs rarely explain current levels of defense in the population. Using the agricultural pest Ipomoea purpurea, we measured correlations between traits involved in defense to glyphosate, the active ingredient in Roundup, a widely used herbicide. We found significant allocation costs of tolerance, as well as trade-offs between resistance and two measures of tolerance to glyphosate. Selection on resistance and tolerance exhibited differing patterns: tolerance to leaf damage was under negative directional selection, whereas resistance was under positive directional selection. The joint pattern of selection on resistance and tolerance to leaf damage indicated the presence of alternate peaks in the fitness landscape such that a combination of either high tolerance and low resistance, or high resistance and low tolerance was favored. The widespread use of this herbicide suggests that it is likely an important selective agent on weed populations. Understanding the evolutionary dynamics of herbicide defense traits is thus of increasing importance in the context of human-mediated evolution.


Successful pregnancy outcome following laparoscopic myomectomy: case report.
Laparoscopic myomectomy is now widely used as an alternative to laparotomy in the management of symptomatic uterine fibroids. The advantages of this minimal access approach outweigh those of the open techniques. The pregnancy outcomes between the two methods have been studied and are comparable, but there still exists a lot of scepticism locally concerning this. It is against this background that we present a 31 year old nulliparous lady who had a two year history of primary infertility secondary to multiple uterine fibroids, the largest being fundal and measuring 6.6cm. She underwent a successful laparoscopic myomectomy in November, 2006 and conceived spontaneously in February 2007. Her antenatal follow up was uneventful. She delivered a live male, 2,650 grams by Caesarean section in October, 2007 and had an unremarkable peuperium. With the availability of proper equipment, instruments, and adequately developing skills, laparoscopic myomectomy is feasible locally and with proper patient selection could result in favourable outcome as it is elsewhere.


The effect of heat treatment on the lactosylation of milk proteins.
Protein lactosylation is a significant modification that occurs during the heat treatment of dairy products, causing changes in proteins' physical-chemical and nutritional properties. Knowledge of the detailed lactosylation information on milk proteins under various heat treatments is important for selecting appropriate thermo-processing and identifying markers to monitor heat load in dairy products. In the present study, we used proteomics techniques to investigate lactosylated proteins under different heating temperatures. We observed a total of 123 lactosylated lysines in 65 proteins, with lactosylation even occurring in raw milk. The number of lactosylated lysines and proteins increased moderately at 75°C to 130°C, but dramatically at 140°C. We found that 6 out of 10, 9 out of 16, 6 out of 12, and 5 out of 15 lysine residues in κ-casein, β-lactoglobulin, α-lactalbumin, and αS1-casein, respectively, were lactosylated under the applied heating treatment. Moreover, different lactosylation states of individual lysines and proteins can indicate the intensity of heating processes. Lactosylation of K14 in β-lactoglobulin could distinguish pasteurized and UHT milk, while lactosylation of lactotransferrin can reflect moderate heat treatment of products.


Analysis of Factors That Influence Patient Satisfaction After Periacetabular Osteotomy: An Asian Cohort Study.
Periacetabular osteotomy (PAO) is an effective joint-preserving procedure for developmental dysplasia of the hip. However, some patients report dissatisfaction after PAO. Because patient satisfaction is increasingly used as a health care quality metric, it is important to gain a better understanding of factors associated with patient satisfaction after PAO. The goal of this study was to investigate patient satisfaction among a cohort of Asian patients undergoing PAO. This study included 227 Asian patients who had undergone PAO at our institution between 1998 and 2016. The study participants completed a questionnaire assessing patient satisfaction, reasons for dissatisfaction, and postoperative Oxford Hip Score (OHS) and University of California, Los Angeles (UCLA), activity scale score. Based on their satisfaction levels, the participants were divided into 4 subgroups, and their demographic characteristics and postoperative patient-reported outcomes were compared. Of the 227 patients, 190 expressed satisfaction that correlated with OHS-pain, OHD-activities of daily living, and UCLA activity scale scores. Primary reasons for dissatisfaction after PAO were persistent pain (24 of 49, 49%), functional limitations (14 of 49, 29%), stiffness around the hip (4 of 49, 8%), unmet expectations (4 of 49, 8%), conversion to total hip arthroplasty (2 of 49, 4%), and complications (1 of 49, 2%). Multivariate analysis showed that preoperative Kellgren-Lawrence grades 1 and 3 were the significant predictive factors for satisfaction and dissatisfaction, respectively. The potential for lower patient satisfaction associated with Kellgren-Lawrence grade 3 because of persistent pain and functional limitations postoperatively suggests that consideration of preoperative severity of osteoarthritis could enhance patient satisfaction after PAO. [Orthopedics. 2022;45(5):297-303.].


Apical dichotomy demonstrated in the angiosperm flagellaria.
An equal dichotomy of an angiosperm vegetative apex, previously suspected on morphological grounds, is demonstrated both externally in whole apices and in histological preparations. Dichotomy is a normal developmental feature with complete continuity in growth from the simple to the bifurcated state. The accessibility of this rare phenomenon in this plant makes further, possibly experimental, approaches feasible.


Acute gall bladder perforation--a dilemma in early diagnosis.
Gall bladder perforation is a rare complication of cholecystitis. A definitive diagnosis is uncommon before surgery and the morbidity and mortality associated with this condition are high. We report six patients with gall bladder perforation to show the difficulty of making an early diagnosis. The history and the clinical findings of these patients are reviewed to highlight diagnostic pitfalls.


The long view: 40 years of Marek's disease research and Avian Pathology.
Marek's disease (MD), named after the Hungarian veterinary pathologist over 100 years ago, is a major disease affecting poultry health worldwide. Research in the late 1960s that led to the identification of the causative herpesvirus and the development of a highly successful vaccine is undoubtedly one of the best success stories in veterinary medicine. As Avian Pathology is celebrating its 40th anniversary, we review the last four decades of MD research that has provided major advances in our understanding of the virus, the pathogenic mechanisms of the disease, methods of diagnosis and the control through different generations of vaccines. Particular attention has been paid to the contributions made by publications in Avian Pathology. Despite this tremendous progress, MD continues to pose major challenges particularly from increasing virulence and emergence of new pathotypes. Further research on the molecular mechanisms of the disease, genetic resistance, vaccine-induced protection and evolution of virulence will be needed to develop more sustainable control strategies in the coming years.


Structure-switching M3L2 Ir(iii) coordination cages with photo-isomerising azo-aromatic linkers.
Cyclotriguaiacylene has been functionalised with 3- or 4-pyridyl-azo-phenyl groups to form a series of molecular hosts with three azobenzene-type groups that exhibit reversible photo-isomerisation. Reaction of the host molecules with [Ir(C^N)2(NCMe)2]+ where C^N is the cyclometallating 2-phenylpyridinato, 2-(4-methylphenyl)pyridinato or 2-(4,5,6-trifluorophenyl)pyridinato results in the self-assembly of a family of five different [{Ir(C^N)2}3(L)2]3+ coordination cages. Photo-irradiation of each of the cages with a high energy laser results in E → Z photo-isomerisation of the pyridyl-azo-phenyl groups with up to 40% of groups isomerising. Isomerisation can be reversed by exposure to blue light. Thus, the cages show reversible structure-switching while maintaining their compositional integrity. This represents the largest photo-induced structural change yet reported for a structurally-integral component of a coordination cage. Energy minimised molecular models indicate a switched cage has a smaller internal space than the initial all-E isomer. The [Ir(C^N)2(NCMe)2]+ cages are weakly emissive, each with a deep blue luminescence at ca. 450 nm.


Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency.
In cortisone reductase deficiency (CRD), activation of cortisone to cortisol does not occur, resulting in adrenocorticotropin-mediated androgen excess and a phenotype resembling polycystic ovary syndrome (PCOS; refs. 1,2). This suggests a defect in the gene HSD11B1 encoding 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), a primary regulator of tissue-specific glucocorticoid bioavailability. We identified intronic mutations in HSD11B1 that resulted in reduced gene transcription in three individuals with CRD. In vivo, 11beta-HSD1 catalyzes the reduction of cortisone to cortisol whereas purified enzyme acts as a dehydrogenase converting cortisol to cortisone. Oxo-reductase activity can be regained using a NADPH-regeneration system and the cytosolic enzyme glucose-6-phosphate dehydrogenase. But the catalytic domain of 11beta-HSD1 faces into the lumen of the endoplasmic reticulum (ER; ref. 6). We hypothesized that endolumenal hexose-6-phosphate dehydrogenase (H6PDH) regenerates NADPH in the ER, thereby influencing directionality of 11beta-HSD1 activity. Mutations in exon 5 of H6PD in individuals with CRD attenuated or abolished H6PDH activity. These individuals have mutations in both HSD11B1 and H6PD in a triallelic digenic model of inheritance, resulting in low 11beta-HSD1 expression and ER NADPH generation with loss of 11beta-HSD1 oxo-reductase activity. CRD defines a new ER-specific redox potential and establishes H6PDH as a potential factor in the pathogenesis of PCOS.


Ume6 Acts as a Stable Platform To Coordinate Repression and Activation of Early Meiosis-Specific Genes in Saccharomyces cerevisiae.
In response to nutrient starvation, the budding yeast Saccharomyces cerevisiae abandons mitotic proliferation and embarks on a differentiation process that leads through meiosis to the formation of haploid spores. This process is driven by cascading waves of meiosis-specific-gene expression. The early meiosis-specific genes are repressed during mitotic proliferation by the DNA-binding protein Ume6 in combination with repressors Rpd3 and Sin3. The expression of meiosis-specific transcription factor Ime1 leads to activation of the early meiosis-specific genes. We investigated the stability and promoter occupancy of Ume6 in sporulating cells and determined that it remains bound to early meiosis-specific gene promoters when those genes are activated. Furthermore, we find that the repressor Rpd3 remains associated with Ume6 after the transactivator Ime1 has joined the complex and that the Gcn5 and Tra1 components of the SAGA complex bind to the promoter of IME2 in an Ime1-dependent fashion to induce transcription of the early meiosis-specific genes. Our investigation supports a model whereby Ume6 provides a platform allowing recruitment of both activating and repressing factors to coordinate the expression of the early meiosis-specific genes in Saccharomyces cerevisiae.


Nonexertional heatstroke. Physiologic management and cooling in 14 patients.
Fourteen patients with nonexertional heatstroke were evaluated in a general hospital during the summer of 1980. They were managed according to a prospectively devised protocol designed to effect heat dissipation primarily via convection and evaporation rather than by conduction. The time from entry into the emergency room to the first recorded rectal temperature of less than 103 degrees F (39.4 degrees C) ranged from 34 to 89 minutes (median, 60 minutes). Only one patient died; none had residual neurologic deficits. The use of these methods can result in a low incidence of permanent neurologic impairment and a low fatality rate.


A clinical trial of intraoperative near-infrared imaging to assess tumor extent and identify residual disease during anterior mediastinal tumor resection.
The management of most solid tumors of the anterior mediastinum involves complete resection. Because of their location near mediastinal structures, wide resection is not possible; therefore, surgeons must use subjective visual and tactile cues to determine disease extent. This clinical trial explored intraoperative near-infrared (NIR) imaging as an approach to improving tumor delineation during mediastinal tumor resection. Twenty-five subjects with anterior mediastinal lesions suspicious for malignancy were enrolled in an open-label feasibility trial. Subjects were administered indocyanine green (ICG) at a dose of 5 mg/kg, 24 hours before resection (via a technique called TumorGlow). The NIR imaging systems included Artemis (Quest, Middenmeer, the Netherlands) and Iridium (VisionSense Corp, Philadelphia, Pennsylvania). Intratumoral ICG uptake was evaluated. The clinical value was determined via an assessment of the ability of NIR imaging to detect phrenic nerve involvement or incomplete resection. Clinical and histopathologic variables were analyzed to determine predictors of tumor fluorescence. No drug-related toxicity was observed. Optical imaging added a mean of 10 minutes to case duration. Among the subjects with solid tumors, 19 of 20 accumulated ICG. Fluorescent tumors included thymomas (n = 13), thymic carcinomas (n = 4), and liposarcomas (n = 2). NIR feedback improved phrenic nerve dissection (n = 4) and identified residual disease (n = 2). There were no false-positives or false-negatives. ICG preferentially accumulated in solid tumors; this was independent of clinical and pathologic variables. NIR imaging for anterior mediastinal neoplasms is safe and feasible. This technology may provide a real-time tool capable of determining tumor extent and specifically identify phrenic nerve involvement and residual disease.


Effects of hypothalamic stimulation on unit responses recorded from neurons of sensorimotor cortex of awake cats during conditioning.
1. The activity of single units of the coronal pericruciate (CPC) cortex was studied in 11 awake cats during sessions in which a click conditioned stimulus (CS) was repeatedly paired with glabella tap unconditioned stimulus (US) and hypothalamic stimulation (HS). Effects of HS on the activity of cortical units were also studied during sessions in which HS alone was delivered repeatedly every 10 s. 2. HS evoked an increase in spike activity of less than 60 ms latency in 89 of 116 units tested. 3. Repeated presentation of HS that was effective in producing rapid behavioral conditioning resulted in a characteristic reduction in the latency of discharge evoked by HS in cortical units. 4. Short-latency activation (less than 20 ms) of units of the sensorimotor cortex appeared to be characteristic of HS that led to enhanced rates of conditioned response (CR) acquisition. One of the cells responding in this way was identified as a pyramidal cell of layer V by intracellular injection of horseradish peroxidase (HRP). 5. Further analyses of activity were performed on 16 units of the CPC cortex that were followed through conditioning (or reconditioning) and extinction of the CR. After less than 10 CS-US-HS pairings, there was a selective augmentation of unit response to the CS but not of response to an explicitly unpaired discriminative stimulus (DS). Responses to the CS were not similarly augmented when presentations of HS preceded rather than followed the presentations of the CS and US. The rapid development of CS-evoked unit activity coincided with the rapid acquisition of discriminative CRs behaviorally. 6. During conditioning, the most conspicuous increases in CS-evoked unit response occurred at latencies 100 ms or more after onset of the click CS. This corresponded with the behavioral observation that the majority of eye blink CRs occurred with onset latencies longer than 100 ms.


Filtering electrocardiogram: Music, math, and ST-elevation myocardial infarction.
Clinicians should have a basic understanding of the working principle of the instruments they use to avoid potential pitfalls caused by post-processing of the acquired biological signals. An electrocardiogram (ECG) is no exception; many different errors can arise during the acquisition or the processing of the ECG data, which may result in dangerous misdiagnoses. We present a case where the use of an inappropriate high-pass filter led to a false diagnosis of ST-elevation myocardial infarction. In addition, this report discusses the basic mechanisms of this frequently overlooked phenomenon and methods to avoid it.


An antithrombotic fucoidan, unlike heparin, does not prolong bleeding time in a murine arterial thrombosis model: a comparative study of Undaria pinnatifida sporophylls and Fucus vesiculosus.
The antithrombotic activities and bleeding effects of selected fucoidans (source from either Undaria pinnatifida sporophylls or from Fucus vesiculosus) have been compared with heparin in the ferric chloride-induced arterial thrombus mouse model. Thrombosis was induced by applying 5% ferric chloride for 3 min on the carotid artery region of Balb/c mouse. Five minutes prior to thrombus induction, mice were infused through the tail vein with either saline (control) or polysaccharides. Either fucoidan or heparin was dosed at 0.1, 1.25, 2.5, 5.0, 10, 25, or 50 mg/kg intravenously (i.v.) The carotid blood flow was monitored until more than 60 min post-thrombus induction. Mouse tail transection bleeding time was measured up to 60 min after making a cut in the mouse tail. Both antithrombotic and bleeding effects were observed in a dose-dependent manner for both fucoidans and heparin. Thrombus formation was totally (reflected by Doppler flow meter) inhibited at either 5 or 50 mg/kg of unfractionated Undaria fucoidan or a low-molecular-weight Undaria fucoidan fraction, respectively, without prolonging the time-to-stop bleeding compared with the control (p < 0.01). The total inhibition of thrombus formation was observed for unfractionated Fucus fucoidan at 25 mg/kg where the time-to-stop bleeding was still significantly prolonged, by as much as 8 ± 1.7 min (p < 0.02). In contrast the heparin-treated group showed total inhibition of thrombus formation even at a small dose of 0.8 mg/kg (400 IU) at which bleeding continued until 60 min. In conclusion algal fucoidans are highly antithrombotic without potential haemorrhagic effects compared with heparin in the arterial thrombus model, but this property differs from algal species to species, and from the molecular structure of fucoidans.


Layer-specific interference with cholinergic signaling in the prefrontal cortex by smoking concentrations of nicotine.
Adolescence is a period in which the developing prefrontal cortex (PFC) is sensitive to maladaptive changes when exposed to nicotine. Nicotine affects PFC function and repeated exposure to nicotine during adolescence impairs attention performance and impulse control during adulthood. Nicotine concentrations experienced by smokers are known to desensitize nicotinic acetylcholine receptors (nAChRs), but the impact thereof on PFC circuits is poorly understood. Here, we investigated how smoking concentrations of nicotine (100-300 nm) interfere with cholinergic signaling in the mouse PFC. nAChR desensitization depends on subunit composition. Since nAChR subunits are differentially expressed across layers of the PFC neuronal network, we hypothesized that cholinergic signaling through nAChRs across layers would suffer differentially from exposure to nicotine. Throughout the PFC, nicotine strongly desensitized responses to ACh in neurons expressing β2* nAChRs, whereas ACh responses mediated by α7 nAChRs were not hampered. The amount of desensitization of β2* nAChR currents depended on neuron type and cortical layer. β2*-mediated responses of interneurons in LII-III and LVI completely desensitized, while cholinergic responses in LV interneurons and LVI pyramidal cells showed less desensitization. This discrepancy depended on α5 subunit expression. Two-photon imaging of neuronal population activity showed that prolonged exposure to nicotine limited cholinergic signaling through β2* nAChRs to deep PFC layers where α5 subunits were expressed. Together, our results demonstrate a layer-dependent decrease in cholinergic activation of the PFC through nAChRs by nicotine. These mechanisms may be one of the first steps leading up to the pathophysiological changes associated with nicotine exposure during adolescence.


Taxonomic reassessment of the genus Dichotomius (Coleoptera: Scarabaeinae) through integrative taxonomy.
Dung beetles of the subfamily Scarabaeinae are widely recognised as important providers of multiple ecosystem services and are currently experiencing revisions that have improved our understanding of higher-level relationships in the subfamily. However, the study of phylogenetic relationships at the level of genus or species is still lagging behind. In this study we investigated the New World beetle genus Dichotomius, one of the richest within the New World Scarabaeinae, using the most comprehensive molecular and morphological dataset for the genus to date (in terms of number of species and individuals). Besides evaluating phylogenetic relationships, we also assessed species delimitation through a novel Bayesian approach (iBPP) that enables morphological and molecular data to be combined. Our findings support the monophyly of the genus Dichotomius but not that of the subgenera Selenocopris and Dichotomius sensu stricto (s.s). Also, our results do not support the recent synonymy of Selenocopris with Luederwaldtinia. Some species-groups within the genus were recovered, and seem associated with elevational distribution. Our species delimitation analyses were largely congruent irrespective of the set of parameters applied, but the most robust results were obtained when molecular and morphological data were combined. Although our current sampling and analyses were not powerful enough to make definite interpretations on the validity of all species evaluated, we can confidently recognise D. nisus, D. belus and D. mamillatus as valid and well differentiated species. Overall, our study provides new insights into the phylogenetic relationships and classification of dung beetles and has broad implications for their systematics and evolutionary analyses.


Synergistic Meropenem-Tobramycin Combination Dosage Regimens against Clinical Hypermutable Pseudomonas aeruginosa at Simulated Epithelial Lining Fluid Concentrations in a Dynamic Biofilm Model.
Exacerbations of chronic Pseudomonas aeruginosa infections are a major treatment challenge in cystic fibrosis due to biofilm formation and hypermutation. We aimed to evaluate different dosage regimens of meropenem and tobramycin as monotherapies and in combination against hypermutable carbapenem-resistant P. aeruginosa A hypermutable P. aeruginosa isolate (meropenem and tobramycin MICs, 8 mg/liter) was investigated in the dynamic CDC biofilm reactor over 120 h. Regimens were meropenem as the standard (2 g every 8 h, 30% epithelial lining fluid [ELF] penetration) and as a continuous infusion (CI; 6 g/day, 30% and 60% ELF penetration) and tobramycin at 10 mg/kg of body weight every 24 h (50% ELF penetration). The time courses of totally susceptible and less-susceptible bacteria and MICs were determined, and antibiotic concentrations were quantified by liquid chromatography-tandem mass spectrometry. All monotherapies failed, with the substantial regrowth of planktonic (>6 log10 CFU/ml) and biofilm (≥6 log10 CFU/cm2) bacteria occurring. Except for the meropenem CI (60% ELF penetration), all monotherapies amplified less-susceptible planktonic and biofilm bacteria by 120 h. The meropenem standard regimen with tobramycin caused initial killing followed by considerable regrowth with resistance (meropenem MIC, 64 mg/liter; tobramycin MIC, 32 mg/liter) for planktonic and biofilm bacteria. The combination containing the meropenem CI at both levels of ELF penetration synergistically suppressed the regrowth of total planktonic bacteria and the resistance of planktonic and biofilm bacteria. The combination with the meropenem CI at 60% ELF penetration, in addition, synergistically suppressed the regrowth of total biofilm bacteria. Standard regimens of meropenem and tobramycin were ineffective against planktonic and biofilm bacteria. The combination with meropenem CI exhibited enhanced bacterial killing and resistance suppression of carbapenem-resistant hypermutable P. aeruginosa.


Prevalence of gender-based and sexual harassment within orthopedic surgery in Canada.
Gender-based and sexual harassment are prevalent in the medical profession. We aimed to quantify the prevalence of such behaviours within orthopedic surgery in Canada and to identify any risk factors for experiencing gender-based or sexual harassment in the workplace. In collaboration with the Canadian Orthopaedic Association, we conducted a Canada-wide email questionnaire survey in June 2019 of all orthopedic surgeons registered with the Canadian Orthopaedic Association and the Canadian Orthopaedic Residents' Association. The development of our questionnaire was informed by a review of the literature and published surveys on gender-based and sexual harassment, and consultation with researchers in intimate partner violence. We conducted a multivariable logistic regression analysis to identify risk factors for harassment. Of the 1783 surgeons invited to participate, 465 returned the questionnaire (response rate 26.1%); the response rate was 48.1% for females and 22.1% for males. Overall, 331/433 respondents (76.4%, 95% confidence interval [CI] 72%-80%) and 315/423 respondents (74.5%, 95% CI 70%-78%) reported having experienced at least 1 occurrence of gender-based and sexual harassment, respectively. Women were significantly more likely than men to have experienced both gender-based and sexual harassment (odds ratio [OR] 16.2, 95% CI 4.8-54.0, and OR 2.2, 95% CI 1.2-4.0, respectively). Respondents who identified as nonwhite were significantly less likely than those who identified as white to have experienced gender-based harassment (OR 0.5, 95% CI 0.3-0.99). The prevalence of gender-based and sexual harassment is high within Canadian orthopedic surgery, and women are at highest risk for experiencing harassment. The results may provide the impetus for orthopedic societies to develop action plans and to re-examine and enforce policies to address these damaging behaviours appropriately.


[Effects of ASPAN's evidence-based clinical practice guidelines for promotion of hypothermia of patients with total knee replacement arthroplasty].
In this study an examination was done of the effects of the American Society of PeriAnesthesia Nurses (ASPAN) Evidence-Based Clinical Practice Guidelines on body temperature, shivering, thermal discomfort, and time to achieve normothermia in patients undergoing total knee replacement arthroplasty (TKRA) under spinal anesthesia. This study was an experimental study with a randomized controlled trial design. Participants (n=60) were patients who underwent TKRA between December 2011 and March 2012. Experimental group (n=30) received active and passive warming measures as described in the ASPAN's guidelines. Control group (n=30) received traditional care. Body temperature, shivering, thermal discomfort, time to achieve normothermia were measured in both groups at 30 minute intervals. Experimental group had slightly higher body temperature compared to control group (p=.002). Thermal discomfort was higher in the experimental group before surgery but higher in the control group after surgery (p=.034). It decreased after surgery (p=.041) in both groups. Time to achieve normothermia was shorter in the experimental group (p=.010). ASPAN's guidelines provide guidance on measuring patient body temperature at regular intervals and on individualized and differentiated hypothermia management which can be very useful in nursing care, particularly in protecting patient safety and improving quality of nursing.


Direct Contact Test for Evaluating Bacterial Growth on Machined and Rough Surface Implants: An In Vitro Study.
To use a modified direct contact test (DCT) to evaluate the bacterial growth on 3 commercially available implants. Streptococcus salivarius growth was tested on 1 machined surface and 2 commercial rough surface implants. Seven implants from each group were fixed to the cover of a 96-well microtiter plate. Bacterial suspension was placed on each implant, and the plate was incubated at 37°C for 1 hour to allow the suspension fluid to evaporate. Fresh medium was added to 7 corresponding wells in the microtiter plate, and the cover holding the implants was placed on the plate to enable immersion of the implant. Noncontaminated implant samples served as control. Bacterial growth was monitored spectrophotometrically at 650 nm for 24 hours. There was a significant S. salivarius growth in all groups of test implants compared with the control. There was no significant difference between bacterial growth kinetics on treated and nontreated implant surfaces (P = 0.241). Using the DCT, we found no difference in bacterial growth between machined and rough surface implants.


Strain analysis and engineering in halide perovskite photovoltaics.
Halide perovskites are a compelling candidate for the next generation of clean-energy-harvesting technologies owing to their low cost, facile fabrication and outstanding semiconductor properties. However, photovoltaic device efficiencies are still below practical limits and long-term stability challenges hinder their practical application. Current evidence suggests that strain in halide perovskites is a key factor in dictating device efficiency and stability. Here we outline the fundamentals of strain within halide perovskites relevant to photovoltaic applications and rationalize approaches to characterize the phenomenon. We examine recent breakthroughs in eliminating the adverse impacts of strain, enhancing both device efficiencies and operational stabilities. Finally, we discuss further challenges and outline future research directions for placing stress and strain studies at the forefront of halide perovskite research. An extensive understanding of strain in halide perovskites is needed, which would allow effective strain management and drive further enhancements in efficiencies and stabilities of perovskite photovoltaics.


Amniotic fluid amino acid concentrations are modified by maternal dietary glucose, gestational age, and fetal growth in rats.
Amniotic fluid (AF) contains free amino acids that enter via transplacental and transmembranous routes from maternal sources; subsequently, the developing fetus "ingests" these amino acids early in gestation through unkeratinized skin and later through continuous AF swallowing. Our objectives were as follows: 1) to determine whether a restriction of maternal dietary glucose modulates the free AF amino acid pool, and 2) to establish whether any diet-induced changes were predictive of fetal weight near term (d 21.5). To produce varying in utero growth rates, pregnant rat dams were fed varying levels of glucose (0, 12, 24, 60%) throughout pregnancy. AF samples, collected on gestational days 18-21, were precolumn derivatized by 9-fluorenylmethyloxychloroformate to produce stable primary and secondary amino acid derivatives required for HPLC detection at low amino acid concentrations. Eighteen amino acids were identified. A 2-way ANOVA with main effects of diet (< or =12% and > or =24% glucose) and gestational age (d 18/19 and 20/21) showed that 2 AF amino acids, methionine and phenylalanine, and 12 AF amino acids were independently modified by diet and gestational age, respectively. Of note were the 364% increase in AF methionine and the constant decline in AF taurine as both gestational age lengthened and fetal weight increased. Multiple regression demonstrated that in addition to methionine, 3 specific AF amino acids, cysteine, lysine, and tyrosine, predicted fetal weight. These results demonstrate that the AF amino acid pool can be modified by the glucose content of the maternal diet and that specific AF amino acids are associated with gestational age and fetal growth.


Diagnosis and follow-up of type 2 diabetes in women with PCOS: a role for OGTT?
Polycystic ovary syndrome (PCOS) is common in premenopausal women. The majority of women with PCOS have insulin resistance and the risk of type 2 diabetes mellitus (T2D) is higher in women with PCOS compared to controls. In non-pregnant women with PCOS, glycemic status may be assessed by oral glucose tolerance test (OGTT), fasting plasma glucose (FPG) or HbA1c. OGTT has been reckoned gold standard test for diagnosing T2D, but OGTT is rarely used for diagnostic purpose in other non-pregnant individuals at risk of T2D, apart from PCOS. OGTT has questionable reproducibility, and high sensitivity of the 2-h glucose value is at the expense of relatively low specificity, especially regarding impaired glucose tolerance (IGT). Furthermore, lean women with PCOS are rarely diagnosed with T2D and only few percent of normal-weight women have prediabetes. Glycemic status is necessary at diagnosis and during follow-up of PCOS, especially in women with high risk of T2D (obesity, previous gestational diabetes (GDM)). We suggest that OGTT should be used in the same situations in PCOS as in other patient groups at risk of T2D. OGTT is indicated for diagnosing GDM; however, OGTT during pregnancy may not be indicated in lean women with PCOS without other risk factors for GDM.


Chloroplast import of four carotenoid biosynthetic enzymes in vitro reveals differential fates prior to membrane binding and oligomeric assembly.
The precursor proteins of the carotenogenic enzymes geranylgeranyl diphosphate synthase, phytoene synthase, phytoene desaturase and lycopene cyclase were imported into isolated pea chloroplasts. Geranylgeranyl diphosphate synthase remained soluble in the stroma in a free form and phytoene synthase associated to thylakoid membranes upon import, both as expected. Surprisingly, phytoene desaturase and lycopene cyclase, which strongly depend on membrane association for enzymatic activity, also remained soluble in the chloroplast stroma. The soluble forms of these enzymes were, however, still competent for membrane-association, e.g. with protein-free liposomal membranes. Indeed the soluble forms of phytoene synthase, phytoene desaturase and lycopene cyclase occurred as ATP- and cold-sensitive high-molecular-mass complexes. Gel-filtration experiments and blue native-PAGE plus autoradiography and western blot analysis indicated a participation of the chloroplast 60-kDa chaperonin (Cpn60) in the soluble high-molecular-mass complexes of imported carotenogenic enzymes. Finally, it was inferred that a membrane-bound regulatory factor plays a decisive role in membrane-binding.


Mediators and moderators of parental involvement on substance use: a national study of adolescents.
Current social developmental theories of drug use often incorporate mediation processes, but it is generally unknown whether these mediation processes generalize across ethnicity and gender. In the present study, we developed a mediation model of substance use based on current theory and research and then tested the extent to which the model was moderated by gender and ethnicity (African American, European American, and Hispanic American), separately for 8th and 10th graders. The respondents were adolescents from the 1994, 1995, and 1996 cohorts of the Monitoring the Future (MTF) project, which conducts yearly in-school surveys with nationally representative samples. Multi-group, structural equation modeling (SEM) results indicated much similarity across gender and ethnicity for school success and time spent with friends as partial mediators of risk taking and parental involvement on drug use (controlling for parental education). However, there were some differences in the magnitude of indirect effects of parental involvement and risk taking on substance use for 8th-grade African American girls. Discussion focuses on the potential success of prevention efforts across different ethnicities and gender that target parent-child relationship improvement and risk taking, and considers possible culture- and gender-specific issues.


Altered expression of heterogenous nuclear ribonucleoproteins and SR factors in human colon adenocarcinomas.
Alternative splicing is part of the expression program of a wide number of genes implicated in cell growth and differentiation. Although the occurrence of inappropriate alternative splicing in tumors has started to emerge, the underlying molecular mechanisms have been, thus far, largely unexplored. We have investigated the alternative splicing pattern of the CD44 gene in specimens of nonfamilial colon adenocarcinomas at different stages of tumor progression. In the same patients, we have assessed by Northern blotting analysis the mRNA levels of different heterogeneous nuclear ribonucleoproteins and SR factors, all involved in pre-mRNA splicing and, more in general, in mRNA maturation. The results of this analysis highlight a general rule for the mode of splicing of the CD44 pre-mRNA. Moreover, we found that the mRNA levels of different SR proteins in tumor specimens are different from, and usually lower than, those detected in samples of nonpathological tissue adjacent to the tumor. Quantitative analysis demonstrates that, in tumors, the mRNA levels of ASF, SRp40, SRp55, and SRp75, when normalized to those of heterogeneous nuclear ribonucleoprotein A1, are lower than those of SRp20 and SRp30. Interestingly, this reduction is more drastic in patients showing a more altered CD44 splicing pattern and seems to be related to the propensity to develop metastases.


Magnetic resonance imaging of the canine abdomen: effect of pulse sequence on diagnostic quality.
Motion artifact is an important limiting factor for abdominal magnetic resonance imaging (MRI) in veterinary patients. The purpose of this study was to determine the effects of pulse sequence on abdominal MRI diagnostic quality in dogs. Ten normal dogs were each scanned using 16 MRI pulse sequences. Sequences included breath-holding sequences, respiratory navigation sequences, and traditional spin-echo sequences. Four observers independently scored diagnostic quality for each sequence based on the appearance of specific organs, overall diagnostic quality, and degree of artifactual interference. Signal-to-noise ratio and contrast-to-noise ratio were also calculated for each sequence. The sequence with the highest overall mean diagnostic quality score was the dorsal T2 turbo spin echo (TSE) with fat saturation and breath-holding. The sequence with the lowest mean diagnostic quality score was the dorsal T2 fast spin echo. The sequence with the highest signal-to-noise ratio for all evaluated organs was the sagittal T1 spin echo. Signal-to-noise and contrast-to-noise ratios did not correlate with subjective assessment of overall diagnostic quality for the majority of the sequences evaluated (P < 0.05). The three sequences considered to have the highest diagnostic quality for the cranial abdomen were the dorsal T2 TSE with fat saturation and breath-hold, transverse T1 turbo fast low-angle shot gradient echo with breath-hold, and dorsal T2 half-Fourier acquisition single shot TSE with respiratory navigation. These sequences had short acquisition times, yielded studies of similar diagnostic quality, provided complementary information, and are therefore recommended for routine canine abdominal MRI protocols.


Lesbian health and the assumption of heterosexuality: an organizational perspective.
This study used a qualitative research design to explore hospital policies and practices and the assumption of female heterosexuality. The assumption of heterosexuality is a product of discursive practices that normalize heterosexuality and individualize lesbian sexual identities. Literature indicates that the assumption of female heterosexuality is implicated in both the invisibility and marked visibility of lesbians as service users. This research adds to existing literature by shifting the focus of study from individual to organizational practices and, in so doing, seeks to uncover hidden truths, explore the functional power of language, and allow for the discovery of what we know and--equally as important--how we know.


Sensitive Mie scattering immunoagglutination assay of porcine reproductive and respiratory syndrome virus (PRRSV) from lung tissue samples in a microfluidic chip.
A microfluidic immunosensor utilizing Mie scattering immunoaggultination assay was developed for rapid and sensitive detection of porcine reproductive and respiratory syndrome virus (PRRSV) from lung tissue samples of domesticated pigs. Antibodies against PRRSV were conjugated to the surface of highly carboxylated polystyrene microparticles (diameter=920nm) and mixed with the diluted PRRSV tissue samples in a Y-shaped microchannel. Antibody-antigen binding induced microparticle immunoagglutination, which was detected by measuring the forward 45° light scattering of 380nm incident beam using microcallipered, proximity fiber optics. For comparison, multi-well experiments were also performed using the same optical detection setup. The detection limit was determined to be 10(-3)TCID(50)ml(-1) for PRRSV dissolved in PBS, while those of previous RT-PCR studies for PRRSV were 10(1)TCID(50)ml(-1) (conventional assays) or <1TCID(50)ml(-1) (quantitative real-time assays). Mie scattering simulations were able to predict the shape of the PRRSV standard curve, indicating that any non-linearity of the standard curve can be interpreted purely as an optical phenomenon. Each assay took less than 5min. A strong correlation could be found between RT-PCR and this method for the lung tissue samples, even though their respective detection mechanisms are different fundamentally (nucleic acids for RT-PCR and virus antigens for light scattering immunoagglutination assay). Several different dilution factors were also tested for tissue samples, and 1/10 and 1/100 were found to be usable. If the microfluidic chips are used only once (i.e. without re-using them), both superior sensitivity and satisfactory specificity can be demonstrated. Specificity studies revealed the presence of Type II PRRSV and non-presence of Type I PRRSV and that the microfluidic chip assay could detect Type II North American strain of PRRSV for the animals tested. This work demonstrates the potential of the Mie scattering immunoassay on a microfluidic chip towards real-time detection system for viral pathogens in domesticated animals.


Resveratrol interferes with N-nitrosodiethylamine-induced hepatocellular carcinoma at early and advanced stages in male Wistar rats.
Resveratrol, a phytochemical compound abundant in red wine and grapes, is known to affect cancer cells both in vitro and in vivo. A great amount of data have indicated the therapeutic benefits of resveratrol against cancer. However, it remains unclear whether these benefits are similar and equally effective in both the early and advanced stages of cancer or carcinogenesis. In this study, we report the effects of resveratrol in the early and advanced stages of hepatocarcinogenesis in a model of N-nitrosodiethylamine (DEN)-induced hepatocellular carcinoma (HCC) of male Wistar rats. For the experiment, rats were divided into different groups and treated with resveratrol either from day 1 of DEN administration for 15 days (pre-HCC), or after the development of HCC, i.e., 15-16 weeks after DEN administration (post-HCC), and compared to untreated HCC-bearing rats. Biochemical analysis of α-fetoprotein, the known serum marker for HCC, and other serum and liver marker enzymes also demonstrated a decreased level upon resveratrol treatment compared to the untreated HCC-bearing rats. H&E staining of tissue sections from the liver showed alteration or transformation of liver parenchymatous tissue in DEN-induced HCC (at 15-16 weeks). Resveratrol treatment during early (on day 1 of DEN-induction) and advanced (weeks 17-18) HCC showed a marked difference in the tissue architecture compared to untreated HCC. Immunoblot analysis revealed that resveratrol intervention at both the early and advanced stages of DEN-induced HCC activated the apoptotic markers, such as PARP cleavage, caspase-3 activation, p53 up-regulation and cytochrome-c release. In addition, semiquantitative RT-PCR and immunoblot analysis demonstrated the up- and down-regulation of key apoptotic regulators, such as Bax and Bcl2, respectively, in a resveratrol treatment-dependent manner. Our results indicate that the administration of resveratrol either at the early or advanced stages of hepatocarcinogenesis is equally effective and involves the activation of the apoptotic pathway in male Wistar rats.


The Anticoagulant and Nonanticoagulant Properties of Heparin.
Heparins represent one of the most frequently used pharmacotherapeutics. Discovered around 1926, routine clinical anticoagulant use of heparin was initiated only after the publication of several seminal papers in the early 1970s by the group of Kakkar. It was shown that heparin prevents venous thromboembolism and mortality from pulmonary embolism in patients after surgery. With the subsequent development of low-molecular-weight heparins and synthetic heparin derivatives, a family of related drugs was created that continues to prove its clinical value in thromboprophylaxis and in prevention of clotting in extracorporeal devices. Fundamental and applied research has revealed a complex pharmacodynamic profile of heparins that goes beyond its anticoagulant use. Recognition of the complex multifaceted beneficial effects of heparin underscores its therapeutic potential in various clinical situations. In this review we focus on the anticoagulant and nonanticoagulant activities of heparin and, where possible, discuss the underlying molecular mechanisms that explain the diversity of heparin's biological actions.


The alphaphone - - a method for measuring thin-film absorption at laser wavelengths.
A sensitive infrasonic method for measuring the absorption of thin films at laser wavelengths has been demonstrated. A fraction of the heat absorbed from the beam by the film passes through a thin layer of gas to the back wall of the Alphaphone, while the remaining absorbed energy heats the supporting window. The gas temperature and pressure rise is then measured with a capacitance microphone. Sensitivity as great as 1.5 x 10(-7) absorption per surface could be achieved with 10 W input by allowing irradiation to continue until the window is saturated with heat. However, the waiting time for saturation even with thin windows would be about 5 min, and with lock-on amplifier demodulation the total measurement time would be several hours. If the chopping speed is increased to 1.5 sec for irradiation and 1.5 sec for cooling, adequate sensitivity of 10(-4) absorption with a signal-to-noise ratio of 9 is achieved with a total measurement time of 1 min. The samples we tested were KRS-5 substrates coated with layers one quarter-wave thick at 10.6 microm. One sample was a single layer of calcium fluoride. Other samples had a layer of zinc sulfide over a binder layer of thorium fluoride. The instrument may be calibrated absolutely with a thin-film heater described large as several percent.


Hyperglycemia with hypogonadism and growth hormone deficiency in a 17-year-old male with H syndrome: the first case report from Syria.
The nucleoside transport capabilities of the human equilibrative nucleoside transporter-3 (hENT3) are disrupted by mutations in SLC29A3 (10q22.2), which are genes for the nucleoside transporter and are the cause of the unusual autosomal recessive disease known as H syndrome. As a result, histiocytic cells invade a number of organs. A 17-year-old Syrian male was admitted to the internal medicine department with a one-month history of polyuria, polydipsia, general weakness, and pallor. He had a history of progressive bilateral sensorineural hearing loss and failure to gain weight for three years. Physical examination revealed various abnormalities, including scrotal mass, small penis and testicles, absence of pubic and axillary hair, joint abnormalities, short stature, hallux valgus, fibrous protrusion near the navel, and hyperpigmented non-itchy painful skin plaques. Clinical signs along with laboratory test results confirmed hyperglycemia, primary hypogonadism, osteopenia, and growth hormone deficiency. After a review of the relevant medical literature, this patient's presentation of hyperglycemia with hypogonadism, hyperpigmentation, hallux valgus, hearing loss, hematological abnormalities, and short stature suggested the diagnosis of H syndrome. The patient received treatment with insulin and testosterone, leading to a significant improvement in his presenting symptoms. H syndrome is a very rare condition, and the fact that the first case has only recently been reported in Syria serves to emphasize how rare it is. H Syndrome should be suspected if a patient has short stature with signs of hyperglycemia and other endocrine and cutaneous abnormalities. We are reporting this case to increase physicians' awareness of this exceedingly rare and unique syndrome.


Herbicide metabolism: N-glycoside of amiben isolated from soybean plants.
The N-glycoside of the herbicide 3-amino-2, 5-dichlorobenzoic acid (amiben) was synthesized in the laboratory. The compound was chromatographically identical with a conjugate of amiben isolated from soybean plants, Glycine Max (L.) Merr. The seeds of a tolerant plant, soybean, and of a susceptible one, barley (Hordeum vulgare L.), were incubated in amiben labeled with carbon-14, and the seedlings were extracted. Essentially all the radioactivity in soybean was present as a compound corresponding to N-glycosyl amiben. Only a small amount of this conjugate was present in barley; most of the radioactivity was present as free amiben or as other unidentified metabolites.


International Union of Pharmacology. XL. Compendium of voltage-gated ion channels: calcium channels.
This summary article presents an overview of the molecular relationships among the voltage-gated calcium channels and a standard nomenclature for them, which is derived from the IUPHAR Compendium of Voltage-Gated Ion Channels. The complete Compendium, including data tables for each member of the calcium channel family can be found at http://www.iuphar-db.org/iuphar-ic/.


Evaluation of Current Equine Influenza Vaccination Protocols Prior to Shipment, Guided by OIE Standards.
To facilitate the temporary importation of horses for competition and racing purposes, with a minimum risk of transmitting equine influenza, the World Organisation for Animal Health (Office International des Epizooties, or OIE), formally engaged in a public-private partnership with the Federation Equestre Internationale (FEI) and the International Federation for Horseracing Authorities (IFHA) to establish, within the context of existing OIE standards, a science-based rationale to identify the ideal time period for equine influenza vaccination prior to shipment. Field trials using vaccines based on different technologies were carried out on three continents. The antibody response post-booster vaccination at intervals aligned with the different rules/recommendations of the OIE, FEI, and IFHA, was monitored by single radial haemolysis. It was determined that 14 days was the optimum period necessary to allow horses adequate time to respond to booster vaccination and for horses that have previously received four or more doses of vaccine and are older than four years, it is adequate to allow vaccination within 180 days of shipment. In contrast, the results indicate that there is a potential benefit to younger (four years old or younger) horses in requiring booster vaccination within 90 days of shipment, consistent with the current OIE standard.


Changes in treatment outcomes of gastric cancer surgery over 45 years at a single institution.
Although many studies have demonstrated improvements in short-and long-term outcomes of gastric cancer surgery, changes in long-term survival over time are not well-established. This study was conducted to evaluate changes in host, tumor, and treatment factors in patients treated at a single institution over a period of 45-yr. We retrospectively evaluated 9282 patients with gastric cancer from 1955 to 1999, and divided the 45-yr into 4 time frames based on published articles: 1955 to 1962 (n=228), 1963 to 1972 (n=891), 1973 to 1988 (n=2789), and 1989 to 1999 (n=5374). Remarkable changes were noted in host, tumor, treatment factors, and prognosis. Among host factors, patients of more advanced age were identified in the 4th period and mean age shifted from 49 to 55 yrs. Among tumor factors, early gastric cancers and upper body tumors increased up to 32% and from 7% to 13%, respectively. An increase in the annual number of patients (from 29 to 649), gastrectomies (from 14 to 600), rate of resection (from 50% to 90%), rate of curative resection (up to 92%), and proportion of total gastrectomy (from 8% to 29%) was noted. Operative mortality was reduced from 6.1% to 0.7%. The overall 5-yr survival rate significantly increased from 22% to 65%. Treatment results of gastric cancer surgery have improved remarkably over the 45-year period. Increase of early stage gastric cancer with early diagnosis considerably influenced the improved survival of patients with gastric cancer.


Ecomorphological diversification of squamates in the Cretaceous.
Squamates (lizards and snakes) are highly successful modern vertebrates, with over 10 000 species. Squamates have a long history, dating back to at least 240 million years ago (Ma), and showing increasing species richness in the Late Cretaceous (84 Ma) and Early Palaeogene (66-55 Ma). We confirm that the major expansion of dietary functional morphology happened before these diversifications, in the mid-Cretaceous, 110-90 Ma. Until that time, squamates had relatively uniform tooth types, which then diversified substantially and ecomorphospace expanded to modern levels. This coincides with the Cretaceous Terrestrial Revolution, when angiosperms began to take over terrestrial ecosystems, providing new roles for plant-eating and pollinating insects, which were, in turn, new sources of food for herbivorous and insectivorous squamates. There was also an early Late Cretaceous (95-90 Ma) rise in jaw size disparity, driven by the diversification of marine squamates, particularly early mosasaurs. These events established modern levels of squamate feeding ecomorphology before the major steps in species diversification, confirming decoupling of diversity and disparity. In fact, squamate feeding ecomorphospace had been partially explored in the Late Jurassic and Early Cretaceous, and jaw innovation in Late Cretaceous squamates involved expansions at the extremes of morphospace.


The beginning of human life and its modern scientific assessment.
One of the most controversial topics in modern bioethics, science, and philosophy is the beginning of individual human life. In the seemingly endless debate, strongly stimulated, by recent technologic advances in human reproduction, a synthesis between scientific data and hypothesis, philosophical thought, and issues of humanities has become a necessity to deal with ethical, juridical, and social problems. Furthermore, in this field there is a temptation to ask science to choose between opinions and beliefs, which neutralize one another. The question of when human life begins requires the essential aid of different forms of knowledge. Here we become involved in the juncture between science and religion, which needs to be carefully explored.


Evolution of Pre- and Post-Copulatory Traits in Male Drosophila melanogaster as a Correlated Response to Selection for Resistance to Cold Stress.
In Drosophila melanogaster the fitness of males depends on a broad array of reproductive traits classified as pre- and post-copulatory traits. Exposure to cold stress, can reduce sperm number, male mating ability and courtship behavior. Therefore, it is expected that the adaptation to cold stress will involve changes in pre- and post-copulatory traits. Such evolution of reproductive traits in response to cold stress is not well studied. We selected replicate populations of D. melanogaster for resistance to cold shock. Over 37-46 generations of selection, we investigated pre- and post-copulatory traits such as mating latency, copulation duration, mating frequency, male fertility, fitness (progeny production) and sperm competitive ability in male flies subjected to cold shock and those not subjected to cold shock. We found that post cold shock, the males from the selected populations had a significantly lower mating latency along with, higher mating frequency, fertility, sperm competitive ability and number of progeny relative to the control populations. While most studies of experimental evolution of cold stress resistance have documented the evolution of survivorship in response to selection, our study clearly shows that adaptation to cold stress involves rapid changes in the pre- and post-copulatory traits. Additionally, improved performances under stressful conditions need not necessarily trade-off with performance under benign conditions.


Effects of 5-lipoxygenase inhibitor zileuton on airway responses to inhaled swine house dust in healthy subjects.
Inhalation of swine house dust induces acute airway inflammation and increased bronchial responsiveness in healthy subjects. The aim of the study was to investigate whether 5-lipoxygenase products such as leukotrienes may have a role in this reaction. Twenty-three healthy subjects were randomised into two groups receiving treatment with either zileuton (600 mg) or placebo four times a day. After 5 days of treatment, all subjects were exposed for 3h in a swine barn. Bronchial responsiveness, exhaled nitric oxide (NO), and mediators in nasal lavage (NAL), blood and urine were measured before and after the exposure. The exposure induced an increased bronchial responsiveness to methacholine in both groups with 2-3 doubling concentration steps, no significant difference between treatments. Leukotriene E(4) in urine increased significantly following exposure in the placebo group from 37.3 (29.1-45.6) (mean (95% confidence interval)) ng/mmol creatinine to 47.7 (36.3-59.0) ng/mmol creatinine (P<0.05), but not in the zileuton group. The post-exposure increase of LTB(4) levels in NAL fluid was totally abolished in the zileuton group (P<0.05 vs. the placebo). The levels of exhaled NO increased significantly (P<0.01), two-fold in both groups. The PGD(2) metabolite 9alpha, 11beta-PGF(2) increased in placebo-treated subjects (P<0.01; P<0.05 vs. zileuton), strengthening mast cell participation. Neutrophil counts and levels of IL-6 in peripheral blood increased in both groups, with a significantly larger increase in zileuton treated subjects (P<0.05 and P<0.001, respectively compared to placebo). Pre-treatment with clinically recommended doses of the 5-lipoxygenase inhibitor zileuton did not affect the increase of bronchial reactivity induced by swine dust exposure. The intervention totally abolished the LTB(4) release in NAL fluid, but only partially inhibited the formation of leukotrienes as monitored by urinary levels. The enhanced increase of neutrophils and IL-6 in peripheral blood in the zileuton group, suggests that inhibition of 5-lipoxygenase may have pro-inflammatory effects.


Two alkaline phosphatase genes positioned in tandem in Bacillus licheniformis MC14 require different RNA polymerase holoenzymes for transcription.
Southern transfer analysis of Bacillus licheniformis MC14 DNA, using as probe a DNA fragment from within the coding region of a previously cloned alkaline phosphatase (APase) gene, revealed a second area of hybridization adjacent to the cloned APase gene. A second APase gene (APase II) was subcloned from the same plasmid clone, pMH8, from which the first APase gene (APase I) had been subcloned. The two genes are arranged in tandem with several hundred base pairs separating them. Immunoblot analysis showed that both code for Mr 60,000 proteins that crossreact with anti-APase. Both proteins enzymatically cleave 5-bromo-4-chloro-3-indolyl phosphate. In vitro transcription showed that APase I and APase II are transcribed in the same direction but that the two genes require different forms of Bacillus RNA polymerase: sigma 55- and sigma 37-containing RNA polymerase holoenzymes, respectively.


Clinical effectiveness of botulinum toxin type B in the treatment of subacromial bursitis or shoulder impingement syndrome.
Subacromial steroid injections are used as a treatment method in subacromial bursitis (SB) or shoulder impingement syndrome (SIS). However, the steroid effect is relatively restricted to the short-term and repeated injections are frequently required, which contributes to unwanted side effects. As an alternative, botulinum toxin (BT) has recently been used for pain relief. This study aimed to investigate the clinical effectiveness of BT type B and to compare this with the effectiveness of steroids. Sixty-one patients diagnosed with SB or SIS were divided into 2 groups and treated with BT type B (BT group) and trimacinolone injection (TA group) under ultrasound guidance, respectively. Numeric Rating Scale (NRS), active shoulder abduction angle, and the Korean version of the score on the Disability of Arm, Shoulder, and Hand (DASH) were measured before the treatment, and at 1 and 3 months after the treatment. Both groups obtained a significant improvement of NRS, DASH, and active shoulder abduction at 1 and 3 months follow-up. BT group showed significantly better outcomes in terms of reduction of NRS and DASH at 3 months than TA group. BT group showed strong trend toward the larger degree of active shoulder abduction than the TA group at 3 months follow-up, as well. Whereas, no significant difference was found in NRS, DASH, and active shoulder abduction between the 2 groups at 1 month follow-up. BT type B can be a useful strategy and has great potential for replacing steroids as a treatment for SB or SIS.


Developing an OSTE to address lapses in learners' professional behavior and an instrument to code educators' responses.
To develop an instrument for measuring medical educators' responses to learners' lapses in professional behavior. In 1999, at the Indiana University School of Medicine, a 22-item checklist of behaviors was developed to describe common responses used by educators responding to learners' lapses in professional behavior. Four medical students were trained to portray lapses in professional behaviors. These students and seven clinical observers trained to categorize behaviors as present or absent. Interrater reliability was assessed during 18 objective structured teaching evaluations (OSTEs). Videotaped OSTEs were coded twice at a one-month interval for test-retest reliability. Items were classified as low, moderate, or high inference behaviors. Script realism and educator effectiveness were assessed. Educators rated OSTE scripts as realistic. Raters observed an average of 6 +/- 2 educator behaviors in reaction to learners' lapses in professional behavior. Educators' responses were rated as moderately effective. More experienced educators attempted more interventions and were more effective. Agreement was high among raters (86% +/- 7%), while intraclass correlation coefficients decreased with increasing inference level. From videotaped OSTEs, raters scored each behavior identically 86% of the time. Accurate feedback on educators' interactions in addressing learners' professionalism is essential for faculty development. Traditionally, educators have felt that faculty's responses to learners' lapses in professional behavior were difficult to observe and categorize. These data suggest that educators' responses to learners' lapses in professional behavior can be defined and reliably coded. This work will help provide objective feedback to faculty when engaging learners about lapses in professional behavior.


Current approaches to the treatment of advanced-stage non-Hodgkin's lymphoma.
Non-Hodgkin's lymphomas (NHLs) are a diverse group of malignant diseases whose clinical behaviour and treatment are distinct from those of Hodgkin's disease. In advanced-stage NHL certain histologic subtypes grow relatively slowly, initially produce few symptoms and, even when untreated, are associated with survival that is usually measured in years. Other, less favourable subtypes grow more rapidly, produce symptoms earlier and result in rapid clinical deterioration and death if aggressive treatment is not begun at the time of diagnosis. Many patients with advanced-stage higher-grade NHL can now expect cure, whereas those with lower-grade NHL cannot. Among the higher-grade lymphomas, factors associated with a poorer prognosis include B symptoms, age greater than 50 years, bulky disease (particularly in the abdomen) and extranodal disease with bone marrow or gastrointestinal involvement. These factors have less effect on prognosis in lower-grade lymphomas. Combination chemotherapy (CT) has been the mainstay of treatment for advanced-stage higher-grade NHL. Newer regimens contain more agents given earlier in the treatment plan. Radiotherapy is a useful supplement to CT in some patients with bulky disease. Most CT regimens have been developed through retrospective uncontrolled studies. Prospective randomized clinical trials must be designed to compare the efficacy of newer, more toxic but seemingly more effective regimens and earlier, less toxic regimens. Such trials should determine which patients may achieve optimal survival results with the least toxic therapy.


An epizootic of avian botulism in a phosphate mine settling pond in northern Florida.
Type C botulism was determined to be the cause of an epizootic among waterfowl and shorebirds in a phosphate mine settling pond in northern Florida during May and June of 1979. Several hundred birds, the most common of which were American coots (Fulica americana), wood ducks (Aix sponsa), common gallinules (Gallinula chloropus), and northern shovelers (Anas clypeata), were afflicted over about a three-week period. A second smaller outbreak occurred in the same pond in early December of 1979. This is apparently the first time that botulism has been reported in waterbirds of Florida.


Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: A 20 year-community study.
Recent population-based data on nonalcoholic fatty liver disease (NAFLD) epidemiology in general, and incidence in particular, are lacking. We examined trends in NAFLD incidence in a U.S. community and the impact of NAFLD on incident metabolic comorbidities (MCs), cardiovascular (CV) events, and mortality. A community cohort of all adults diagnosed with NAFLD in Olmsted County, Minnesota, between 1997 and 2014 was constructed using the Rochester Epidemiology Project database. The yearly incidence rate were calculated. The impact of NAFLD on incident MCs, CV events, and mortality was studied using a multistate model, with a 4:1 age- and sex-matched general population as a reference. We identified 3,869 NAFLD subjects (median age, 53; 52% women) and 15,209 controls; median follow-up was 7 (1-20) years. NAFLD incidence increased 5-fold, from 62 to 329 in 100,000 person-years. The increase was highest (7-fold) in young adults, aged 18-39 years. The 10-year mortality was higher in NAFLD subjects (10.2%) than controls (7.6%; P < 0.0001). NAFLD was an independent risk factor for incident MCs and death. Mortality risk decreased as the number of incident MCs increased: relative risk (RR) = 2.16 (95% confidence [CI], 1.41-3.31), 1.99 (95% CI, 1.48-2.66), 1.75 (95% CI, 1.42-2.14), and 1.08 (95% CI, 0.89-1.30) when 0, 1, 2, or 3 MCs were present, respectively. The NAFLD impact on CV events was significant only in subjects without MCs (RR = 1.96; 95% CI = 1.35-2.86). NAFLD reduced life expectancy by 4 years, with more time spent in high metabolic burden. Incidence of NAFLD diagnosis in the community has increased 5-fold, particularly in young adults. NAFLD is a consequence, but also a precursor of MC. Incident MC attenuates the impact of NAFLD on death and annuls its impact on CV disease. (Hepatology 2018;67:1726-1736).


Real-world outcomes among patients with early rapidly progressive rheumatoid arthritis.
To characterize treatment patterns, healthcare resource utilization (HRU), and disease activity among patients with early rapidly progressive rheumatoid arthritis (eRPRA) in the United States when treated with a first-line biologic disease-modifying antirheumatic drug (bDMARD) tumor necrosis factor-α (TNF) inhibitor or first-line abatacept. Observational, multicenter, retrospective, longitudinal, medical records-based, cohort study. Patients with eRPRA were identified by anti-citrullinated protein antibody positivity, 28-joint Disease Activity Score-C-reactive protein of 3.2 or greater, symptomatic synovitis in 2 or more joints for at least 8 weeks prior to the index date, and onset of symptoms within 2 years or less of the index date. Patients received abatacept or a TNF inhibitor as first-line treatment. Patient characteristics, treatment patterns, HRU, and disease activity following bDMARD initiation were compared across the 2 groups. Odds ratios (ORs) of HRU in the first 6 months of bDMARD treatment were estimated using multivariable logistic regression to adjust for patient mix. There were 60 patients treated with abatacept and 192 treated with a TNF inhibitor in the first line. Those treated with first-line abatacept had lower adjusted odds of hospitalization (OR, 0.42; 95% CI, 0.18-0.95), emergency department (ED) visits (OR, 0.39; 95% CI, 0.16-0.93), and magnetic resonance imaging (MRI) (OR, 0.45; 95% CI, 0.21-0.97) than those treated with a first-line TNF inhibitor (all P <.05). Adjusted odds of achieving low disease activity as measured by clinical disease activity index within 100 days of bDMARD initiation favored first-line abatacept versus a first-line TNF inhibitor (OR, 4.37; 95% CI, 1.34-13.94; P = .01). Adjusting for disease severity, patients with eRPRA who were treated with first-line abatacept were less likely to have hospitalizations, ED visits, and MRI use during the first 6 months of bDMARD treatment and more likely to achieve low disease activity within 100 days of bDMARD start compared with those who received a first-line TNF inhibitor.


Effects of an oral administration of glucosamine-chondroitin-quercetin glucoside on the synovial fluid properties in patients with osteoarthritis and rheumatoid arthritis.
The effects of an orally administered combination of a glucosamine-chondroitin-quercetin glucoside (GCQG) supplement on the synovial fluid properties of patients with osteoarthritis (OA) and rheumatoid arthritis (RA) were investigated from the clinical nutrition view point. In this study, forty-six OA and twenty-two RA patients were administered with the GCQG supplement orally for 3 months. Several parameters of the knee joints were monitored before and after supplementation. The OA patients showed a significant improvement in pain symptoms, daily activities (walking and climbing up and down stairs), and visual analogue scale, and changes in the synovial fluid properties with respect to the protein concentration, molecular size of hyaluronic acid, and chondroitin 6-sulphate concentration were also observed. However, no such effects were observed in the RA patients. These results suggest that the GCQG supplement exerted a special effect on improving the synovial fluid properties in OA patients.


The herpes simplex virus ribonucleotide reductase is required for ocular virulence.
We used a herpes simplex virus (HSV) type 1 ribonucleotide reductase (RR) null mutant (ICP6 delta) to study the role of HSV-1 RR in ocular HSV infections. We found that ICP6 delta was unable to induce vascularization of the cornea or stromal keratitis following inoculation into the cornea of BALB/c mice, but was able to induce a transient mild blepharitis. The parental strain (HSV-1 KOS) and a revertant of ICP6 delta, ICP6 delta+3.1, both caused severe ocular disease, indicating that HSV-1 RR is required for ocular virulence in mice. ICP6 delta grew poorly in vitro (Vero and BALB/c 3T3 fibroblasts) and in vivo (eye, trigeminal ganglia and brain) compared to ICP6 delta+3.1 and HSV-1 KOS, suggesting that the avirulence of ICP6 delta is due to poor growth in the host. ICP6 delta also grew less well in primary human corneal fibroblasts, suggesting that RR may be required for virulence in humans. These results indicate that drugs inhibiting the function of RR might be effective in treating ocular HSV infections.


Combinatorial RNAi: a winning strategy for the race against evolving targets?
The ability to use double-stranded RNA to inhibit gene expression sequence-specifically (RNA interference, or RNAi) is currently revolutionizing science and medicine alike. Numerous pre-clinical studies are evaluating RNAi as a novel therapeutic modality in the battle against gain-of-function autosomal dominant diseases, cancer, and viral infections. One emerging concern is that RNAi mono-therapies might ultimately fail to control viruses that can escape silencing by mutation and/or RNAi suppression. Thus, sophisticated strategies are being developed that aim to avert viral resistance by combining RNAi effectors with each other or with further gene expression inhibitors. Several reports already validate this new concept of "combinatorial RNAi" (coRNAi) and illustrate its versatility by describing co-expression of RNAi triggers directed against single or multiple, viral or cellular, targets. Other studies document the successful delivery of these triggers with additional RNA- or protein-based silencers. Moreover, vectors have been engineered to blend RNAi-mediated gene inhibition with conventional gene replacement strategies. Collectively, these efforts open up exciting new therapeutic avenues but could also augment the inherent risks of RNAi technology, including immune responses, off-targeting, and oversaturation of endogenous pathways. Here, we critically review all coRNAi strategies and discuss the requirements for their transition into clinical application.


Solitary Asymptomatic Thyroid Metastasis from Hepatocellular Carcinoma Detected by FDG-PET/CT.
Thyroid metastases from hepatocellular carcinoma (HCC) seldom occur and are often difficult to diagnose because of their asymptomatic clinical course. We evaluated a very rare case of solitary thyroid metastasis from HCC that showed high uptake of fluorine-18 fluorodeoxyglucose (FDG), when imaged using fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). The patient was a 74-year-old man and presented with a remarkably elevated des-gamma-carboxy prothrombin level of 1,157 mAU/ml 22 months after hepatic lobectomy. FDG-PET/CT imaging revealed a hypodense tumor with high FDG uptake, with a maximum standardized uptake value of 5.2 in the thyroid left lobe. Solitary thyroid metastasis from HCC was suspected and subsequent fine needle aspiration did indeed reveal HCC. The patient received left thyroidectomy with left regional lymph node dissection. Two months after left thyroidectomy, contrast-enhanced computed tomography showed local recurrence, and the patient received ongoing radiotherapy treatment. To our knowledge, the present study is the first to demonstrate the feasibility of FDG-PET/CT in the diagnosis and management of clinically diagnosed, asymptomatic, solitary thyroid metastasis from HCC.


Suppression of T(h)1 cell activation and prevention of autoimmune diabetes in NOD mice by local expression of viral IL-10.
Insulin-dependent diabetes mellitus in the NOD mouse model is caused by the T cell-mediated autoimmune destruction of pancreatic beta cells. Viral IL-10 (vIL-10), encoded in the Epstein-Barr virus genome, shares many of the anti-inflammatory properties of cellular IL-10, but lacks its immunostimulatory properties. In the present study, we generated transgenic (Tg) NOD mice in which vIL-10 was produced exclusively in pancreatic islets and investigated the effect of vIL-10 on the development of diabetes. The accumulation of lymphocytes around islets was more prominent, but the invasive insulitis decreased in the vIL-10 Tg mice. The incidence of diabetes was markedly reduced in the vIL-10 Tg mice, in clear contrast to the accelerated diabetes seen in the murine IL-10 Tg NOD mice. IL-12p40 and IFN-gamma mRNA levels were decreased in pancreata of the vIL-10 Tg mice, although CD4 mRNA level was markedly increased. These results suggest that locally produced vIL-10 induced leukocyte migration, but inhibited the activation of T(h)1, probably through suppressing the production of IL-12. They indicate that vIL-10 may well be superior to cellular IL-10 in the treatment of autoimmune diabetes. The vIL-10 Tg NOD mice should provide a useful tool for understanding the differential action of vIL-10 versus cellular IL-10.


The adaptor molecules LAT and SLP-76 are specifically targeted by Yersinia to inhibit T cell activation.
T cell responses are critical to the survival of Yersinia-infected animals. Yersinia have the ability to directly suppress T lymphocyte activation through the virulence factor YopH, a tyrosine phosphatase. Using single cell video microscopy and FACS analysis, here we show that even an average of one Yersinia per T cell is sufficient to inhibit or alter T cell responses. This efficient inhibition is traced to specific targeting by YopH of the adaptor proteins, linker for activation of T cells (LAT) and SH2-domain-containing leukocyte protein of 76 kD (SLP-76), which are crucial for T cell antigen receptor (TCR) signaling. A catalytically inactive YopH translocated via the type III secretory pathway from the bacteria into T cells primarily binds to LAT and SLP-76. Furthermore, among the proteins of the TCR signaling pathway, the tyrosine phosphorylation levels of LAT and SLP-76 are the most affected in T cells exposed to low numbers of Yersinia pseudotuberculosis. This is the first example showing that a pathogen targets these adaptor proteins in the TCR signaling pathway, suggesting a novel mechanism by which pathogens may efficiently alter T cell-mediated immune responses.


Connecting to Internet--search tools.
The amount of information on the Internet is growing by the nanosecond. It is no longer expeditious to "surf" site to site now that automated convenient-to-use search tools can find the information you are looking for swiftly. Unfortunately, no one tool covers the entire worldwide web (www), much less the entire Internet. The following describes the components and characteristics of popular Internet search tools.


Untangling membrane rearrangement in the nidovirales.
All known positive sense single-stranded RNA viruses induce host cell membrane rearrangement for purposes of aiding viral genome replication and transcription. Members of the Nidovirales order are no exception, inducing intricate regions of double membrane vesicles and convoluted membranes crucial for the production of viral progeny. Although these structures have been well studied for some members of this order, much remains unclear regarding the biogenesis of these rearranged membranes. Here, we discuss what is known about these structures and their formation, compare some of the driving viral proteins behind this process across the nidovirus order, and examine possible routes of mechanism by which membrane rearrangement may occur.


Neural grafting to experimental neocortical infarcts improves behavioral outcome and reduces thalamic atrophy in rats housed in enriched but not in standard environments.
The purpose of this study was to evaluate whether grafting of fetal neocortical tissue 1 week after focal brain ischemia improved behavioral outcome and reduced secondary thalamic atrophy. One week after distal ligation of the right middle cerebral artery in spontaneously hypertensive male rats, blocks of fetal neocortex (embryonic day 17) were homografted to rats housed in standard or enriched environments. Control infarcted nongrafted rats were housed in the enriched environment. Behavioral outcome was repeatedly tested until the rats were killed 20 weeks after the ligation. Ten days earlier, a mixture of 2% Fluoro-Gold and 10% biotinylated dextran amine was injected into the transplants for retrograde and anterograde tracing of graft-host connections. Grafted and nongrafted rats with enriched housing performed significantly better than grafted rats with standard housing on a rotating pole and a prehensile traction test. Grafted "enriched" rats were moreover significantly better than grafted "standard" rats and nongrafted enriched rats in a rotation test and a postural and locomotor tail position test. In the latter test, nongrafted enriched rats performed significantly better than grafted standard rats. The lesion-induced atrophy in posterior thalamus with its major sensorimotor cortex relay nuclei was significantly reduced in grafted enriched rats compared with nongrafted enriched rats. Afferent and efferent graft-host connections were identified in both grafted groups. Graft volumes did not differ. Neural grafting enhanced functional outcome and reduced thalamic atrophy only when combined with housing in enriched environments.


Long-term Persistence of an Extensively Drug-Resistant Subclade of Globally Distributed Pseudomonas aeruginosa Clonal Complex 446 in an Academic Medical Center.
Antimicrobial resistance (AMR) is a major challenge in the treatment of infections caused by Pseudomonas aeruginosa. Highly drug-resistant infections are disproportionally caused by a small subset of globally distributed P. aeruginosa sequence types (STs), termed "high-risk clones." We noted that clonal complex (CC) 446 (which includes STs 298 and 446) isolates were repeatedly cultured at 1 medical center and asked whether this lineage might constitute an emerging high-risk clone. We searched P. aeruginosa genomes from collections available from several institutions and from a public database for the presence of CC446 isolates. We determined antibacterial susceptibility using microbroth dilution and examined genome sequences to characterize the population structure of CC446 and investigate the genetic basis of AMR. CC446 was globally distributed over 5 continents. CC446 isolates demonstrated high rates of AMR, with 51.9% (28/54) being multidrug-resistant (MDR) and 53.6% of these (15/28) being extensively drug-resistant (XDR). Phylogenetic analysis revealed that most MDR/XDR isolates belonged to a subclade of ST298 (designated ST298*) of which 100% (21/21) were MDR and 61.9% (13/21) were XDR. XDR ST298* was identified repeatedly and consistently at a single academic medical center from 2001 through 2017. These isolates harbored a large plasmid that carries a novel antibiotic resistance integron. CC446 isolates are globally distributed with multiple occurrences of high AMR. The subclade ST298* is responsible for a prolonged epidemic (≥16 years) of XDR infections at an academic medical center. These findings indicate that CC446 is an emerging high-risk clone deserving further surveillance.


Association of presence/absence and on/off patterns of Helicobacter pylori oipA gene with peptic ulcer disease and gastric cancer risks: a meta-analysis.
There are increasing studies examining the relationship between the status of H. pylori oipA gene and peptic ulcer disease (PUD) and gastric cancer (GC) but the results turn out to be controversial. We attempted to clarify whether oipA gene status is linked with PUD and/or GC risks. A systematically literature search was performed through four electronic databases. According to the specific inclusion and exclusion criteria, seven articles were ultimately available for the meta-analysis of oipA presence/absence with PUD and GC, and eleven articles were included for the meta-analysis of oipA on/off status with PUD and GC. For the on/off functional status analysis of oipA gene, the "on" status showed significant associations with increased risks of PUD (OR = 3.97, 95% CI: 2.89, 5.45; P < 0.001) and GC (OR = 2.43, 95% CI: 1.45, 4.07; P = 0.001) compared with gastritis and functional dyspepsia controls. Results of the homogeneity test indicated different effects of oipA "on" status on PUD risk between children and adult subgroups and on GC risk between PCR-sequencing and immunoblot subgroups. For the presence/absence analysis of oipA gene, we found null association of the presence of oipA gene with the risks of PUD (OR = 1.93, 95% CI: 0.60, 6.25; P = 0.278) and GC (OR = 2.09, 95% CI: 0.51, 8.66; P = 0.308) compared with gastritis and functional dyspepsia controls. To be concluded, when oipA exists, the functional "on" status of this gene showed association with increased risks for PUD and GC compared with gastritis and FD controls. However, merely investigating the presence/absence of oipA would overlook the importance of its functional on/off status and would not be reliable to predict risks of PUD and GC. Further large-scale and well-designed studies concerning on/off status of oipA are required to confirm our meta-analysis results.


MET oncogene aberrant expression in canine osteosarcoma.
The objective of this study was to investigate the role of the MET oncogene in canine osteosarcoma. Seven large-breed dogs affected by spontaneous skeletal osteosarcoma underwent en bloc tumor excision. Total RNA was extracted from frozen tumor samples and assessed for expression of the MET oncogene by Northern blot analysis. Five of seven biopsy samples expressed high levels of the MET oncogene; its expression in the primary tumors was comparable with that previously identified in primary osteosarcomas in humans. A lung metastasis from one of the dogs expressed MET at a higher level than did its primary tumor. Spontaneously arising osteosarcoma in dogs clinically and pathologically mimics the corresponding disease in humans. We previously demonstrated that the MET oncogene was aberrantly expressed in a high percentage of human osteosarcomas. The results of the current study also provide a molecular parallel between the tumors in dogs and humans. This in vivo model may be helpful in evaluating new strategies for therapy against osteosarcoma.


Screening for Chlamydial and Gonococcal Infections: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
The 2014 US Preventive Services Task Force (USPSTF) recommendation statement supported the effectiveness of screening for chlamydia and gonorrhea in asymptomatic, sexually active women 24 years or younger and in older women at increased risk for infection, although evidence for screening in men was insufficient. To update the 2014 USPSTF review on screening for chlamydial and gonococcal infection in adults and adolescents, including those who are pregnant. Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Ovid MEDLINE (January 1, 2014, through May 28, 2020) with surveillance through May 21, 2021. Randomized clinical trials and observational studies of screening effectiveness, accuracy of risk stratification and alternative screening methods, accuracy of tests, and screening harms. One investigator abstracted data; a second checked accuracy. Two investigators independently assessed study quality. Complications of infection; infection transmission or acquisition; diagnostic accuracy of anatomical site-specific testing and collection methods; screening harms. Twenty-seven studies were included (N = 179 515). Chlamydia screening compared with no screening was significantly associated with reduced risk of pelvic inflammatory disease (PID) in 2 of 4 trials and with reduced hospital-diagnosed PID (0.24% vs 0.38%); relative risk, 0.6 [95% CI, 0.4-1.0]), but not clinic-diagnosed PID or epididymitis, in the largest trial. In studies of risk prediction instruments in asymptomatic women, age younger than 22 years demonstrated comparable accuracy to extensive criteria. Sensitivity of chlamydial testing was similar at endocervical (89%-100%) and self- and clinician-collected vaginal (90%-100%) sites for women and at meatal (100%), urethral (99%), and rectal (92%) sites for men but lower at pharyngeal sites (69.2%) for men who have sex with men. Sensitivity of gonococcal testing was 89% or greater for all anatomical samples. False-positive and false-negative testing rates were low across anatomical sites and collection methods. Screening for chlamydial infection was significantly associated with a lower risk of PID in young women. Risk prediction criteria demonstrated limited accuracy beyond age. Testing for asymptomatic chlamydial and gonococcal infections was highly accurate at most anatomical sites, including urine and self-collected specimens. Effectiveness of screening in men and during pregnancy, optimal screening intervals, and adverse effects of screening require further evaluation.


Chilling followed by incubation at 37 degrees causes a flow of 3H-choline labeled phospholipids from nuclear-associated endoplasmic reticulum to other endomembranes of L-cells.
The exposure of L-cells to a period of 15 min incubation in ice followed by a return to normal culture conditions caused distinct alterations in the distribution pattern of 3H-choline incorporation in phospholipids in subcellular fractions. The amount of radioactivity appearing in the nuclei and nuclear-associated endoplasmic reticulum decreased while that in the mitochondrial and endoplasmic reticulum membrane fractions increased, suggesting a precursor-product relationship. These changes appeared to occur in a linear fashion. Furthermore, the increase in radioactivity in individual endoplasmic reticulum subfractions differed in that label increased fivefold in light rough membranes but only about twofold in the HR and S subfractions.


Characteristics of craniofacial morphology and factors affecting them in patients with isolated cleft palate.
Myriad maxillo-mandibular occlusal relationships are observed in patients with isolated cleft palate (ICP), unlike in patients with other cleft types, such as cleft lip and palate. This study aimed to categorise the characteristics of craniofacial morphology in patients with ICP, and investigate the clinical factors affecting these categorised morphological characteristics. Thirty-six girls with ICP (age (mean ± SD): 5.36 ± 0.36 years) underwent cephalometric measurement. Their craniofacial morphology was categorised using cluster analysis. Profilograms were created and superimposed onto the standard Japanese profilograms to visualise the morphological characteristics of each group (cluster). The mean values and variations in the linear and angular measurements of each group were compared with the Japanese standards and statistically analysed using Dunnett's test after the analysis of variance. Fisher's exact test was used to analyse the differences between the cleft types (cleft in the hard and/or soft palate) and skills of the operating surgeons in the groups. Cluster analysis of craniofacial morphologies in patients with ICP resulted in the formation of three categories: the first cluster exhibited a relatively harmonious anteroposterior relationship between the maxilla and the mandible (22.2%); the second cluster exhibited crossbite owing to a significantly smaller maxilla (33.3%); and the third cluster exhibited a smaller mandible with posterior rotation showing skeletal class II malocclusion (44.4%). Differences in cleft types and surgeons were not associated with the distribution of patients in each cluster. Patients with ICP exhibited characteristic morphological patterns, such as bimaxillary retrusion or severe mandibular retrusion, besides the anterior crossbite frequently found in patients with cleft lip and palate . Understanding the typical morphological characteristics could enable better diagnostic categorisation of patients with ICP, which may eventually improve orthodontic treatment planning.


Carbohydrate intake modulates the effect of the ABCA1-R230C variant on HDL cholesterol concentrations in premenopausal women.
The R230C variant of the ATP-binding cassette transporter A1 (ABCA1) gene has been consistently associated with decreased HDL-cholesterol (HDL-C) concentrations in several studies in the Mexican mestizo population. However, information on how diet composition modifies the effect of the ABCA1-R230C variant on HDL-C concentrations is very scarce. The aim of the present study was to analyze whether the effect of ABCA1-R230C on HDL-C concentrations is modulated by dietary factors in a nationwide population sample of 3591 adults from the National Health and Nutrition Survey conducted by the State's Employees' Social Security and Social Services Institute. All participants answered a validated questionnaire to assess health status and weekly food consumption. Fasting blood samples were drawn for biochemical analysis and DNA extraction, and the ABCA1-R230C variant was genotyped using TaqMan assays. Statistical analyses consisted of simple linear and multiple regression modeling adjusting for age, BMI, smoking, and alcohol consumption. The overall C risk allele frequency was 9.3% and the variant was significantly associated with low HDL-C concentrations in both sexes. A significant negative correlation between carbohydrate consumption and HDL-C concentrations was observed in women bearing the R230C variant (P = 0.021) and a significant gene-diet interaction was found only in premenopausal women (P = 0.037). In conclusion, the effect of the ABCA1-R230C gene variant on HDL-C concentrations is modulated by carbohydrate intake in premenopausal women. This finding may help design optimized dietary interventions according to sex and ABCA1-R230C genotype.


Lactobacillus reuteri supplements do not affect salivary IgA or cytokine levels in healthy subjects: A randomized, double-blind, placebo-controlled, cross-over trial.
To evaluate the effect of daily ingestion of probiotic lactobacilli on the levels of secretory IgA (sIgA) and selected cytokines in whole saliva of healthy young adults. The study group consisted of 47 healthy adults (18-32 years) who volunteered for a randomized, double-blind, placebo-controlled, cross-over trial after informed consent. During intervention, the subjects ingested two lozenges per day containing two strains of the probiotic bacterium Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) or placebo lozenges. The intervention and wash-out periods were 3 weeks. Saliva samples were collected at baseline, immediately after each intervention period and 3 weeks post-intervention. ELISA was used to measure sIgA and luminex technology was used to measure the interleukins (IL)-1β, IL-6, IL-8 and IL-10. For statistical analyses a mixed ANOVA model was employed to calculate changes in the salivary outcome variables. Forty-one subjects completed the study and reported a good compliance. No significant differences in the concentrations of salivary sIgA or cytokines were recorded between the L. reuteri and placebo interventions or between baseline and 3 weeks post-intervention levels. No side- or adverse effects were reported. Supplementation with two strains of the probiotic L. reuteri did not affect sIgA or cytokine levels in whole saliva in healthy young adults. The results thereby indicate that daily oral supplementation with L. reuteri do not seem to modulate the salivary oral immune response in healthy young subjects (ClinicalTrials.gov NCT02017886).