Efficacy and safety of three different opioid-based immobilisation combinations in blesbok (Damaliscus pygargus phillipsi).
African wildlife species are increasingly being immobilised with combinations of a low dose of potent opioids combined with medetomidine and azaperone. The physiological effects of these combinations in comparison to conventional potent opioidazaperone combinations have scarcely been evaluated. In this cross-over study conducted on eight captive blesbok, we compared the physiological variables of blesbok immobilised with 2 mg of thiafentanil + 10 mg of azaperone (TA); 0.5 mg thiafentanil + 1.5 mg medetomidine (TM), and 0.5 mg thiafentanil + 1.5. mg medetomidine + 10 mg azaperone (TMA). Thiafentanil's effects were antagonised with naltrexone at 10 mg naltrexone per mg thiafentanil, and the medetomidine effects with atipamezole at 5 mg atipamezole per mg medetomidine. The physiological variables were compared between treatment groups using descriptive statistics and repeated measures ANOVA. The TA combination resulted in the shortest induction and recovery times, higher heart rates, respiratory rates, PaO2, SpO2, and lower MAP and A-a gradients, but with less muscle relaxation. The TM and TMA combinations caused marked bradycardia and hypoxaemia. The hypoxaemia was most severe in animals immobilised with TMA, and four of eight blesbok immobilised had a PaO2 < 35 mmHg at the 10- or 15-minute sampling point. These blesbok were provided supplementary oxygen, which corrected the hypoxaemia. The TA combinations caused the lowest degree of physiological compromise. All three combinations were effective for the immobilisation of blesbok, but as the low-dose thiafentanil and high-dose medetomidine combinations caused marked hypoxaemia, supplementary oxygen is recommended when using these combinations.


Effects of Cyberbullying Experience and Cyberbullying Tendency on School Violence in Early Adolescence.
School violence in early adolescence, whose frequency and status have recently changed significantly. This study attempts to detect the cyber bullying inclination of youth in early adolescence when aggressiveness reaches its peak, to identify school violence, and to develop a school violence prevention program. Method: This study was a survey research, investigating participants who were 470 middle school students in South Korea. For the analysis, independent t-test, one-way ANOVA and hierarchical regression analysis. It is suggested that the school violence victimization experience and cyber bullying infliction experience has an influence in the school violence infliction. And the cyber bullying victimization experience and school violence victimization experience variables exert effects. The results of this study suggest that school nurses who are connecting to the community-school-home should take an active part in the development of school violence mediation education program, considering the cultural characteristics of the country.


Interactions of membrane active peptides with planar supported bilayers: an impedance spectroscopy study.
Membrane active peptides exert their biological effects by interacting directly with a cell's lipid bilayer membrane. These therapeutically promising peptides have demonstrated a variety of activities including antimicrobial, cytolytic, membrane translocating, and cell penetrating activities. Here, we use electrochemical impedance spectroscopy (EIS) on polymer-cushioned supported lipid bilayers constructed on single crystal silicon to study two pairs of closely related membrane active peptides selected from rationally designed, combinatorial libraries to have different activities in lipid bilayers: translocation, permeabilization, or no activity. Using EIS, we observed that binding of a membrane translocating peptide to the lipid bilayer resulted in a small decrease in membrane resistance followed by a recovery back to the original value. The recovery may be directly attributable to peptide translocation. A nontranslocating peptide did not decrease the resistance. The other pair, two membrane permeabilizing peptides, caused an exponential decrease of membrane resistance in a concentration-dependent manner. This permeabilization of the supported bilayer occurs at peptide to lipid ratios as much as 1000-fold lower than that needed to observe effects in vesicle leakage assays and gives new insights into the fundamental peptide-bilayer interactions involved in membrane permeabilization.


Retrospective analysis of ploidy in primary osseous and extraosseous Ewing family tumors in children.
To retrospectively study the DNA content in a series of childhood Ewing Family Tumors (EFT), and to investigate its prognostic value. The study was performed on a series of 27 EFTs (osseous Ewing's sarcoma, 18 cases; extraosseous Ewing's sarcoma, 2; peripheral neuroepithelioma, 4; Askin Rosai tumors, 3). Ploidy was investigated using both flow cytometry (FCM) and image cytometry (ICM) on tumor cell suspensions from formalin-fixed paraffin-embedded specimens or fresh frozen tissue obtained from the primary tumor at diagnosis. Ploidy was evaluable by FCM in all cases, and by ICM in 23/27. When fresh frozen tissue and paraffin-embedded samples from the same tumor were available for analysis, they yielded equal results. The rate of agreement between FCM and ICM was 82%. The majority of cases were diploid, and in the present series aneuploidy seemed to be associated with a poor outcome. These results suggest that aneuploidy could be an indicator of a bad prognosis in EFT; however, the small number of cases precludes any conclusion of statistical value. Larger retrospective studies on ploidy using archival material could be performed and their reliability is supported by the concordance of results from fresh and formalin-fixed tissue.


Paclitaxel-Induced Src Activation Is Inhibited by Dasatinib Treatment, Independently of Cancer Stem Cell Properties, in a Mouse Model of Ovarian Cancer.
Approximately seventy percent of ovarian cancer patients succumb to the disease within the first 5 years of diagnosis, even after successful surgery and effective chemotherapy treatment. A small subset of chemotherapy resistant cancer stem cells (CSCs) cause relapse of ovarian cancers. This study investigated the association between paclitaxel-mediated Src activation (p-Src) and CSC populations in driving ovarian cancer progression. We demonstrate that patients with high-stage serous ovarian carcinomas have significantly elevated levels of p-Src, compared to patient with low-stage and benign ovarian tumours. Additionally, p-Src was significantly enhanced in ascites-derived tumour cells obtained from recurrent patients, compared to chemonaïve patients. Paclitaxel treatment increased Src activation in ovarian cancer cells, causing enrichment of CSC marker expression in the surviving cells in vitro and in xenografts of nude mice. Dasatinib in combination with paclitaxel significantly suppressed p-Src in ovarian cancer cell lines and xenografts but had no effect on the expression of CSC markers. However, combination of paclitaxel and Dasatinib showed lower trend in invasion in liver and pancreas, compared to paclitaxel-only treatment. The tumours treated with combination therapy also had significantly lower infiltration of mononuclear cells. Robust recurrent tumour growth was observed in all mice groups after termination of treatments. The above results suggest that Dasatinib-mediated inhibition of p-Src may not be crucial for paclitaxel-induced CSC-mediated recurrence in ovarian cancer.


Rate coefficient of the reaction CH2OO + NO2 probed with a quantum-cascade laser near 11 μm.
The reaction of the simplest Criegee intermediate CH2OO with NO2 is considered to be important in atmospheric chemistry because of its prospective contribution to the decay of CH2OO and the additional source of NO3, hence its effects on the NOx and HOx cycles. The reported rate coefficients of this reaction varied by a factor of 5. Employing a cw quantum-cascade laser with wavelength near 11 μm coupled with Herriott mirrors to probe CH2OO sensitively, we investigated in detail the reaction CH2OO + NO2 under total pressure 5.9-9.7 Torr at 298 K and reported a rate coefficient kNO2 = (1.0 ± 0.2) × 10-12 cm3 molecule-1 s-1, about one-seventh the value determined with direct measurements of CH2OO by Weltz et al. This smaller rate coefficient implies that the title reaction contributes to the atmospheric source of NO3 and the decay of CH2OO much less than previously conceived.


Mortality among production workers in pulp and paper mills.
A cohort of 3,572 pulp and paper mill workers employed for at least one year between 1945 and 1955 was followed through 31 March 1977. Vital status was determined for 99% of the cohort. The 915 deaths observed were 79% of the number expected on the basis of comparable United States mortality rates. Statistically nonsignificant excesses of deaths due to lymphosarcoma and reticulosarcoma and to stomach cancer were observed. These findings tend to corroborate reports based on state vital statistics, and preliminary case-referent and population-based studies of workers in the pulp or paper industries. No deaths due to nasal cancer were observed, but only 0.6 were expected. When process-specific analyses were conducted, the excess risk of lymphosarcoma and reticulosarcoma was increased only for men who worked in sulfate mills. The excess risk of stomach cancer was limited to men who worked in sulfite mills. Process-specific standardized mortality ratios for these causes were highest after 20 years since first employment in the mills.


Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice.
Recent studies have identified sex-differences in auditory physiology and in the susceptibility to noise-induced hearing loss (NIHL). We hypothesize that 17β-estradiol (E2), a known modulator of auditory physiology, may underpin sex-differences in the response to noise trauma. Here, we gonadectomized B6CBAF1/J mice and used a combination of electrophysiological and histological techniques to study the effects of estrogen replacement on peripheral auditory physiology in the absence of noise exposure and on protection from NIHL. Functional analysis of auditory physiology in gonadectomized female mice revealed that E2-treatment modulated the peripheral response to sound in the absence of changes to the endocochlear potential compared to vehicle-treatment. E2-replacement in gonadectomized female mice protected against hearing loss following permanent threshold shift (PTS)- and temporary threshold shift (TTS)-inducing noise exposures. Histological analysis of the cochlear tissue revealed that E2-replacement mitigated outer hair cell loss and cochlear synaptopathy following noise exposure compared to vehicle-treatment. Lastly, using fluorescent in situ hybridization, we demonstrate co-localization of estrogen receptor-2 with type-1C, high threshold spiral ganglion neurons, suggesting that the observed protection from cochlear synaptopathy may occur through E2-mediated preservation of these neurons. Taken together, these data indicate the estrogen signaling pathways may be harnessed for the prevention and treatment of NIHL.


Beneficial effects of the active principle component of Korean cabbage kimchi via increasing nitric oxide production and suppressing inflammation in the aorta of apoE knockout mice.
The present study investigated the effects of 3'-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid (HDMPPA), the active principle compound of kimchi, on vascular damage in the experimental atherosclerotic animal. HDMPPA was administrated by an intraperitoneal injection of 10 mg/kg per d for 8 weeks to apoE knockout (KO) mice with an atherogenic diet containing 1 % cholesterol, and its effects were compared with vehicle-treated control mice. HDMPPA increased NO content in the aorta, accompanied by a decrease in reactive oxygen species (ROS) concentration. Furthermore, in the HDMPPA-treated group, aortic endothelial NO synthase (eNOS) expression was up-regulated compared with the control group. These results suggested that HDMPPA could maintain NO bioavailability through an increasing eNOS expression and preventing NO degradation by ROS. Furthermore, HDMPPA treatment in apoE KO mice inhibited eNOS uncoupling through an increase in vascular tetrahydrobiopterin content and a decrease in serum asymmetric dimethylarginine levels. Moreover, HDMPPA ameliorates inflammatory-related protein expression in the aorta of apoE KO mice. Therefore, the present study suggests that HDMPPA, the active compound of kimchi, a Korean functional food, may exert its vascular protective effect through the preservation of NO bioavailability and suppression of the inflammatory response.


Evaluation of single root canals filled using the lateral compaction, tagger's hybrid, microseal and guttaflow techniques.
The aim of this study was to determine the percentage of voids, gutta-percha and root canal sealer using 4 different filling techniques. Fifty-two extracted maxillary lateral incisors were prepared using the crown-down pressureless technique. The teeth were randomly divided in 4 groups (n=13): Lateral compaction (LC), Tagger's hybrid (TH), MicroSeal (MS) and GuttaFlow (GF) techniques. Horizontal cross-sections were made at the 2, 10 and 15 mm levels from the apex. Digital images of the root canal areas were acquired using a stereomicroscope and examined using the Image Tool 3.0 software. Statistical analysis was performed using the Kruskal-Wallis test (α=0.05). In general, a significant decrease in the gutta-percha filled area and increase of sealer area were observed at the apical level for all the evaluated techniques (p<0.05). With regard to the presence of voids, no significant difference was found. MS and TH techniques showed a larger gutta-percha filled area than LC and GF techniques at the coronal and middle third level (p<0.05). From the results of the present study, it may be concluded that the gutta-percha filled area of fillings decrease at the apical level, regardless of the filling technique used.


Newly Diagnosed Celiac Disease and Bone Health in Young Adults: A Systematic Literature Review.
Celiac disease (CD), a gluten-induced autoimmune disease, is associated with low bone mineral density (BMD) among children. Unfortunately, it is often diagnosed in adulthood, which may lead to an increased risk of fragile bones. The aim of this systematic review was to report on BMD status among young adults newly diagnosed with CD, and to examine the effect of a gluten-free diet (GFD), nutritional supplements, such as vitamin D, or antiresorptive medications on BMD recovery. Databases searched were Medline, Embase, and Cochrane Library up to July 2nd, 2020. Both observational studies and clinical trials were considered, if patients were newly diagnosed and between 20 and 35 years of age and reported on BMD. We critically appraised the identified studies using ROBINS-I and summarized the findings narratively. Out of 3991 references, we identified 3 eligible studies: one cross-sectional study and two longitudinal studies. In total, 188 patients were included, and the study population consisted primarily of women with an age range between 29 and 37 years old. Compared to healthy controls, our target population had lower BMD. Moreover, a strict GFD may increase BMD during a follow-up period of up to 5 years. Newly diagnosed CD patients aged 20-35 years are at risk of lower BMD. Therefore, it may be crucial to assess BMD at time of diagnosis in young women. Whether the results can be extrapolated to young men is unknown. While strict GFD may improve BMD over time, there is a lack of robust evidence to demonstrate that nutritional supplements or antiresorptive agents are beneficial in the prevention of fragile bones in this age group.


Till multiculturalism do us part: Multicultural policies and the national identification of immigrants in European countries.
How do multicultural policies affect immigrants' identification with the country of destination? Theory suggests that these policies may have two opposite effects and either widen or diminish the gap between the national identification of natives and immigrants. In addition to these opposite effects, I expect that the effects of multicultural policies are also diverse depending on immigrants' cultural and social distance from the host society. In this study, immigrants are categorised based on generations and origins. Using newly constructed measurements for multicultural policies, as well as European Social Survey Round 7 with 20 European countries, I conduct a multilevel analysis. The results indicate that multicultural policies diminish the gap between the national identification of natives and immigrants. However, these effects are evident only for non-European immigrants and not for European immigrants. Furthermore, I find no evidence that the effects differ for the first and second generations.


Membrane physiology of retinal glial (Müller) cells.
Electrophysiological techniques were used to determine the ion selectivity properties and the spatial distribution of the membrane conductance of amphibian Müller cells. Membrane potential changes recorded during ion substitution experiments in frog (Rana pipiens) retinal slices demonstrated that the Müller cell K+:Na+ membrane permeability ratio is approximately 490:1 and that cell Cl- permeability is extremely low. In frog retinal slices, Müller cell input resistance was 8.5 megohms when measured in the inner plexiform layer and 4.8 megohms when measured in the optic fiber layer. Intact, enzymatically dissociated salamander (Ambystoma tigrinum) cells had an input resistance of 7.9 megohms, whereas cells lacking their endfoot process (removed by surgical microdissection or by shearing force) had a resistance of 152 megohms. Pressure ejection of a 100 mM K+ solution near the proximal surface of the endfeet of dissociated salamander cells produced depolarizations 7 times greater than did ejections near the lateral face of the endfoot and 24 to 50 times greater than did ejections near other cell regions. Similar K+ ejection results were obtained from Müller cells in salamander and frog retinal slices. Taken together, these results demonstrate that in both the frog and the salamander, approximately 95% of the total membrane conductance of Müller cells is localized in the cell's endfoot process. In salamander, the specific membrane resistance of the endfoot membrane was estimated to be 32 ohm X cm2 whereas the specific resistance of the remainder of the cell was 7300 ohm X cm2. This remarkably nonuniform conductance distribution has important consequences for theories concerning K+ regulation in the retina and for mechanisms underlying electroretinogram generation.


Protection against singlet oxygen, the main actor of sebum squalene peroxidation during sun exposure, using Commiphora myrrha essential oil.
Squalene is a component of sebum. Both are directly exposed to the external environment and play a key role in skin physiology. They are particularly prone to photo oxidation during sun exposure. We studied the impact of two types of antioxidant on sebum squalene peroxidation by UV irradiation. The first type is free radical scavenger (Butyl hydroxyl toluene and an olive extract rich in hydroxytyrosol). The second type is the essential oil of Commipora myrrha, a singlet oxygen quencher. These properties were confirmed using the 2,2-diphenyl-1-picrylhydrazyl test for antiradical capacity [Yoshida et al. (1989) Chem. Pharm. Bull., 37, 1919; Buenger et al. (2006) Int. J. Cosmet. Sci., 28, 135] and 1,3-diphenylisobenzofuran test for the capacity to quench singlet oxygen [Kochewar and Redmond (2000) Meth. Enzymol., 28, 319; Racine and Auffray (2005) Fitoterapia, 76, 316]. Furthermore, we have extended an ex vivo method to classify the efficacy of cosmetics to protect squalene by collecting sebum in vivo and irradiating it in a controlled way. The squalene monohydroperoxide formation is monitored by high performance liquid chromatography. This methods allows us to compare the efficiency of the three antioxidants at 0.6% in a cosmetic formulation to protect squalene from photo oxidation. Our results clearly show that essential oil of Commiphora myrrha provides the best protection against squalene peroxidation. These results demonstrate that squalene peroxidation during solar exposure is mainly because of singlet oxygen and not due to free radical attack. This suggests that sun care cosmetics should make use not only of free radical scavengers but also of singlet oxygen quenchers.


Comparative fecal metagenomics unveils unique functional capacity of the swine gut.
Uncovering the taxonomic composition and functional capacity within the swine gut microbial consortia is of great importance to animal physiology and health as well as to food and water safety due to the presence of human pathogens in pig feces. Nonetheless, limited information on the functional diversity of the swine gut microbiome is available. Analysis of 637, 722 pyrosequencing reads (130 megabases) generated from Yorkshire pig fecal DNA extracts was performed to help better understand the microbial diversity and largely unknown functional capacity of the swine gut microbiome. Swine fecal metagenomic sequences were annotated using both MG-RAST and JGI IMG/M-ER pipelines. Taxonomic analysis of metagenomic reads indicated that swine fecal microbiomes were dominated by Firmicutes and Bacteroidetes phyla. At a finer phylogenetic resolution, Prevotella spp. dominated the swine fecal metagenome, while some genes associated with Treponema and Anareovibrio species were found to be exclusively within the pig fecal metagenomic sequences analyzed. Functional analysis revealed that carbohydrate metabolism was the most abundant SEED subsystem, representing 13% of the swine metagenome. Genes associated with stress, virulence, cell wall and cell capsule were also abundant. Virulence factors associated with antibiotic resistance genes with highest sequence homology to genes in Bacteroidetes, Clostridia, and Methanosarcina were numerous within the gene families unique to the swine fecal metagenomes. Other abundant proteins unique to the distal swine gut shared high sequence homology to putative carbohydrate membrane transporters. The results from this metagenomic survey demonstrated the presence of genes associated with resistance to antibiotics and carbohydrate metabolism suggesting that the swine gut microbiome may be shaped by husbandry practices.


Imaging of monoamine oxidase-A in the human brain with [11C]befloxatone: quantification strategies and correlation with mRNA transcription maps.
[C]Befloxatone is a highly specific, reversible, and selective radioligand for brain PET imaging of monoamine oxidase-A and can be quantified by a two-tissue compartment model (2TCM) and an arterial input function. The aims of the present study were the following: (a) to assess whether in-vivo protein concentration, as measured by [C]befloxatone total distribution volume (VT), is correlated with post-mortem mRNA expression; (b) to replicate in a population of tobacco smokers the results of a recent study on healthy nonsmokers, which showed that spectral analysis (SA) provides a highly accurate estimation of [C]befloxatone-VT at the voxel level; and (c) to validate the use of an input function that would not require arterial sampling. Healthy male nonsmokers (n=7) and smokers (n=8) were imaged with PET and [C]befloxatone. Binding was quantified at the regional and voxel level with the Logan plot, multilinear analysis (MA1), and SA. VT values were compared with the reference values obtained by 2TCM at the regional level. [C]Befloxatone binding was compared with mRNA transcription maps from the Allen Human Brain Atlas. A less-invasive input function was obtained with a population-based input function (PBIF) scaled with arterialized venous samples. mRNA expression was highly correlated with in-vivo 2TCM-VT values both for nonsmokers (R=0.873; P<0.0001) and for smokers (R=0.851; P<0.0001). At the regional level, both Logan and MA1 showed a moderate negative bias (-5 to -10%) compared with the reference VT values. With the exception of a single outlying individual, SA showed little bias and variability (+4.4±3.5%). Although variability was higher than at the regional level, SA provided the most accurate VT estimations at the voxel level: all but one participant had an error of less than 20%. Parametric Logan and MA1 analyses gave highly biased or unusable results. PBIF provided good results in all participants in whom the arterialization of venous blood was successful (all errors of about 10% or less). [C]Befloxatone binding is strongly correlated with the values of mRNA transcription measured in post-mortem brains. At the voxel level, SA is the best available choice for [C]befloxatone quantification, although a higher variability must be expected. When an arterial input function is not technically feasible, a PBIF scaled with arterialized venous samples may provide an acceptable alternative, provided an optimal arterialization can be achieved.


Optical Coherence Tomography for Online Guidance of Complex Coronary Interventions.
Decision making on lesion preparation and stent/scaffold optimization are cornerstones of patient outcome. Intravascular imaging recently emerged as a critical modality to achieve better results of stent/scaffold implantation and superior clinical outcomes compared with coronary angiography alone. Optical coherence tomography (OCT), a light-based intravascular imaging modality with high frame rate in acquisition and very high speed pullback, can interrogate the target vessel in a couple of seconds, and immediately display a pristine longitudinal lumen contour with automatic detection of lesion severity, site and lumen/stent areas. Further, OCT provides pivotal information on sites of calcium, with accurate measurements of the minimum distance from the lumen, a major determinant of stent/scaffold underexpansion, malapposition and eccentricity. Finally, to guide the PCI procedure using OCT without operator misjudgment, a real-time point-to-point correspondence between angiographic and OCT images has been recently created. Co-registration of OCT with angiography with direct tableside control of acquisition and analysis enables the operator to plan and map optimal stent/scaffold implantation. To prove the clinical relevance of OCT-guided PCI, simple, standardized interventional planning, including pre- and postprocedural automatic lumen detection metrics, has to be translated into effective treatment flow algorithms. A similar OCT algorithm is being tested in the ongoing prospective, randomized, multicenter ILUMIEN III study, to demonstrate that OCT-guided stent placement is superior to angiography-guided and non-inferior to IVUS-guided stent implantation. (Circ J 2016; 80: 2063-2072).


[Duodenal polyps. Incidence, histologic substrate and significance].
378 duodenal polyps were identified by endoscopic biopsy since 1973 in the course of more than 25,000 oesophago-gastro-duodenoscopies, corresponding to an incidence rate of 1.5%. Heterotopias of the gastric mucosa and so-called inflammatory polyps were most frequent (35.7% and 35.2%, respectively), followed by hyperplasia of Brunner's glands (6.9%), lipid islets (2.9%) and lymphatic hyperplasia (1.8%). Histologically there was no correlate to the endoscopic findings. Hence, non-neoplastic polyps account for about 90% of duodenal polyps; they are harmless and generally produce no (or only minor) signs or symptoms. Clinically relevant polyps besides the primary and secondary malignant processes are the adenomas of the colon type (6.9%) and Peutz-Jeghers polyps (1.3%). Since these two may occur in gastrointestinal polyposis, "top-and-tail endoscopy" must be performed. The rate of complications of 15% in endoscopic loopectomy in the duodenum is clearly higher than that in the stomach and colon.


Risks of herpes zoster in patients with rheumatoid arthritis according to biologic disease-modifying therapy.
To evaluate whether the risks of herpes zoster (HZ) differed by biologic agents with different mechanisms of action (MOAs) in older rheumatoid arthritis (RA) patients. Using Medicare data from 2006-2011, among RA patients with prior biologic agent use and no history of cancer or other autoimmune diseases, this retrospective cohort study identified new treatment episodes of abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Followup started on initiation of the new biologic agent and ended at any of the following: first incidence of HZ, a 30-day gap in current exposure, death, a diagnosis of other autoimmune disease or cancer, loss of insurance coverage, or December 31, 2011. We calculated the proportion of RA patients vaccinated for HZ in each calendar year prior to biologic agent initiation and HZ incidence rate for each biologic agent. We compared HZ risks among therapies using Cox regression adjusted for potential confounders. Of 29,129 new biologic treatment episodes, 28.7% used abatacept, 15.9% adalimumab, 14.8% rituximab, 12.4% infliximab, 12.2% etanercept, 6.1% tocilizumab, 5.8% certolizumab, and 4.4% golimumab. The proportion of RA patients vaccinated for HZ prior to biologic agent initiation ranged from 0.4% in 2007 to 4.1% in 2011. We identified 423 HZ diagnoses with the highest HZ incidence rate for certolizumab (2.45 per 100 person-years) and the lowest for golimumab (1.61 per 100 person-years). Neither the crude incidence rate nor the adjusted hazard ratio differed significantly among biologic agents. Glucocorticoid use had a significant association with HZ. Among older patients with RA, the HZ risk was similar across biologic agents, including those with different MOAs.


Linked Sources of Neural Noise Contribute to Age-related Cognitive Decline.
Healthy aging is associated with a multitude of structural changes in the brain. These physical age-related changes are accompanied by increased variability in neural activity of all kinds, and this increased variability, collectively referred to as "neural noise," is argued to contribute to age-related cognitive decline. In this study, we examine the relationship between two particular types of neural noise in aging. We recorded scalp EEG from younger (20-30 years old) and older (60-70 years old) adults performing a spatial visual discrimination task. First, we used the 1/f-like exponent of the EEG power spectrum, a putative marker of neural noise, to assess baseline shifts toward a noisier state in aging. Next, we examined age-related decreases in the trial-by-trial consistency of visual stimulus processing. Finally, we examined to what extent these two age-related noise markers are related, hypothesizing that greater baseline noise would increase the variability of stimulus-evoked responses. We found that visual cortical baseline noise was higher in older adults, and the consistency of older adults' oscillatory alpha (8-12 Hz) phase responses to visual targets was also lower than that of younger adults. Crucially, older adults with the highest levels of baseline noise also had the least consistent alpha phase responses, whereas younger adults with more consistent phase responses achieved better behavioral performance. These results establish a link between tonic neural noise and stimulus-associated neural variability in aging. Moreover, they suggest that tonic age-related increases in baseline noise might diminish sensory processing and, as a result, subsequent cognitive performance.


Enhancement of erythrocyte superoxide dismutase activity: effects on cellular oxidant defense.
To delineate further the role of superoxide dismutase (SOD) in red blood cell (RBC) oxidant defense, normal human erythrocytes were osmotically lysed and resealed in the presence of varying concentrations of exogenous SOD. This resulted in a dose-dependent increase in SOD activity in the resealed erythrocytes while maintaining nearly normal RBC hemoglobin concentration (less than 10% decrease from the control value), cell volume, and cellular deformability. Surprisingly, a five- or ninefold increase in SOD activity yielded no additional protection against superoxide-generating drugs (phenazine methosulfate or menadione sodium bisulfite). No significant differences were observed between the control and SOD-loaded RBCs in O2-driven methemoglobin formation or generation of thiobarbituric acid-reactive substances. In contrast, RBCs with elevated SOD activity pretreated with sodium azide (to block catalase activity) or 1-chloro-2,4-dinitrobenzene (to deplete reduced glutathione, GSH) showed significantly enhanced methemoglobin generation in response to superoxide generating drugs. No differential response was noted between the control, control-resealed, and SOD-loaded RBCs to oxidants other than superoxide. Based on our results and other data, we conclude that elevated SOD activity may imbalance cellular oxidant defense, resulting in enhanced oxidation due to the accelerated generation of H2O2, the product of O2- dismutation. This effect is significantly exacerbated under conditions in which H2O2 catabolism is altered.


[Anomalous temperature dependence of the activity of immobilized alpha-chymotrypsin preparations].
Catalytic activity of alpha-chymotrypsin preparations covalently included in the matrix of the poly-N-isopropylacrylamide gel does not follow Arrhenius equation above the low critical temperature of the polymer dissolution. Starting from this temperature, at which the changes of polymer structure takes place (hydrophobization), the temperature increase results in a rate lowering for the chemical reaction catalyzed by the enzyme. This phenomenon is reversible. A correlation between temperature dependence of the immobilized alpha-chymotrypsin activity and the dehydration degree of the carrier is observed. The decrease of the water content in the matrix causes a change of the substrate specificity of the immobilized alpha-chymotrypsin.


Abnormal attentional internetwork link in dyslexic readers.
Attention ability can be divided into three separate networks (executive, orienting, and alerting) that differ in their function and neurobiology. It has been suggested that the right temporal parietal junction (TPJ) can gate between the orienting and the alerting systems. Because there is converging evidence suggesting that the right TPJ functions abnormally in dyslexia, the current work examines behaviorally the independence of the orienting and the alerting systems in dyslexic readers. The Attention Network Test (ANT) is a nonlinguistic test designed to measure behaviorally the separate attention systems using a single test. One feature of the ANT test is that it captures the separability and independence of the normal attention networks. In the current study, dyslexic readers preformed the ANT test and their performance was compared with normal readers. Here we demonstrate, consistent with previous theories, impairment in executive and orienting networks in dyslexic readers; however, for the first time, we reveal unique situations in which the orienting spatial attention system in dyslexia is abnormally dependent on and negatively correlated with the alerting attention system. Dyslexics suffer from globally spread abnormal nonlinguistic attentional networks in what are considered separate attentional systems in the normal population; it appears that they are abnormally interrelated in the dyslexic population.


Tree reconciliation combined with subsampling improves large scale inference of orthologous group hierarchies.
An orthologous group (OG) comprises a set of orthologous and paralogous genes that share a last common ancestor (LCA). OGs are defined with respect to a chosen taxonomic level, which delimits the position of the LCA in time to a specified speciation event. A hierarchy of OGs expands on this notion, connecting more general OGs, distant in time, to more recent, fine-grained OGs, thereby spanning multiple levels of the tree of life. Large scale inference of OG hierarchies with independently computed taxonomic levels can suffer from inconsistencies between successive levels, such as the position in time of a duplication event. This can be due to confounding genetic signal or algorithmic limitations. Importantly, inconsistencies limit the potential use of OGs for functional annotation and third-party applications. Here we present a new methodology to ensure hierarchical consistency of OGs across taxonomic levels. To resolve an inconsistency, we subsample the protein space of the OG members and perform gene tree-species tree reconciliation for each sampling. Differently from previous approaches, by subsampling the protein space, we avoid the notoriously difficult task of accurately building and reconciling very large phylogenies. We implement the method into a high-throughput pipeline and apply it to the eggNOG database. We use independent protein domain definitions to validate its performance. The presented consistency pipeline shows that, contrary to previous limitations, tree reconciliation can be a useful instrument for the construction of OG hierarchies. The key lies in the combination of sampling smaller trees and aggregating their reconciliations for robustness. Results show comparable or greater performance to previous pipelines. The code is available on Github at: https://github.com/meringlab/og_consistency_pipeline .


In quest of contact: phylogeography of helmeted terrapins (Pelomedusa galeata, P. subrufa sensu stricto).
Based on rangewide sampling and three mitochondrial and two nuclear markers (together up to 1,850 bp and 1,840 bp, respectively), we examine the phylogeography of two helmeted terrapin species (Pelomedusa galeata and P. subrufa sensu stricto) and infer shifts of climatically suitable spaces since the Last Glacial Maximum using a modeling approach. Whilst P. galeata displays significant phylogeographic structuring across its range and consists of two deeply divergent lineages that could represent distinct species, P. subrufa shows no obvious phylogeographic differentiation. This seems to be related to historically stable or fluctuating ranges. One of the lineages within P. galeata appears to be confined to the westernmost, winter-rainfall region of South Africa and deserves special conservational attention due to the scarcity of surface water. The other lineage is distributed further east and is differentiated in three weakly supported subclades with parapatric distribution; one occurring inland, and two along the south and east coasts, respectively. As far as is known, P. subrufa occurs in South Africa only in the northeast of the country (Limpopo, Mpumalanga) and we report the species for the first time from the Lapalala Wilderness Area in the Waterberg region (Limpopo), approximately 350 km further west than previously recorded. We confirmed the occurrence of P. galeata only 80 km south of Lapalala. Thus, a sympatric occurrence of P. galeata and P. subrufa is possible. Another putative contact zone, for the two lineages within P. galeata, must be located in the Western Cape region, and further contact zones are likely for the eastern subclades within P. galeata. The nuclear loci provided no evidence for gene flow across taxa or genetic clusters within taxa. Future investigations should use denser sampling from putative contact zones and more nuclear markers to re-examine this situation. Despite few phylogeographic studies published for southern African biota, it seems likely that differentiation follows general rules, and that climate and physiographic barriers (e.g., the Great Escarpment) have shaped phylogeographic patterns.


Mycoplasmas and acholeplasmas isolated from ducks and their possible association with pasteurellas.
Two hundred and sixty-three cases of clinically diseased ducks of all ages were examined for the presence of mycoplasmas. Mycoplasmas and acholeplasmas belonging to more than eight serogroups were cultured from 68 of them, and comprised 12 M anatis, one M columbinasale, two M gallinaceum, two M gallinarum, nine M synoviae, three unidentified Mycoplasma species, 37 Acholeplasma laidlawii and one unclassified acholeplasma belonging to each of serogroups 7 and 8. They were identified by biochemical characterisation, disc growth inhibition and agar gel diffusion tests. Fifty-three (78 per cent) of the isolates occurred with species of Pasteurella: 33.8 per cent with Pasteurella anatipestifer, 32.4 per cent with P multocida and 11.8 per cent with both P anatipestifer and P multocida. Nine of the isolates (13.2 per cent) were in pure culture and six (8.8 per cent) with other agents. Of the ducks negative for mycoplasmas 33.3 per cent were infected with P anatipestifer, 25.1 per cent with P multocida and 14.4 per cent with both P anatipestifer and P multocida. There was no correlation between the infections with mycoplasmas and P anatipestifer but there was a weak association between the infections with mycoplasmas, especially M anatis and P multocida.


[The study of the relationship between diet and primary liver cancer].
Two dietary surveys were carried out in a high prevalence area of primary liver cancer (PLC) and a low PLC area in the Guangxi Zhuang Autonomous Region of China in 1987 and 1988 respectively. The results of these two surveys were similar and no statistical significant differences were observed. They showed that negative correlations between the mortality rates of PLC and the intake amount of rice, fruit, vegetable, energy, protein, crude fiber and ascorbic acid existed. However, between the mortality rates of PLC and the intake of corn, and peanut oil, positive correlations were noted. The aflatoxin content of corn, peanut and peanut oil was greater than that of rice, hence the possible relationship between aflatoxin and PLC. It suggested that diet and nutrients could affect PLC mortality rates.


A Model-Based Approach for Identifying Functional Intergenic Transcribed Regions and Noncoding RNAs.
With advances in transcript profiling, the presence of transcriptional activities in intergenic regions has been well established. However, whether intergenic expression reflects transcriptional noise or activity of novel genes remains unclear. We identified intergenic transcribed regions (ITRs) in 15 diverse flowering plant species and found that the amount of intergenic expression correlates with genome size, a pattern that could be expected if intergenic expression is largely nonfunctional. To further assess the functionality of ITRs, we first built machine learning models using Arabidopsis thaliana as a model that accurately distinguish functional sequences (benchmark protein-coding and RNA genes) and likely nonfunctional ones (pseudogenes and unexpressed intergenic regions) by integrating 93 biochemical, evolutionary, and sequence-structure features. Next, by applying the models genome-wide, we found that 4,427 ITRs (38%) and 796 annotated ncRNAs (44%) had features significantly similar to benchmark protein-coding or RNA genes and thus were likely parts of functional genes. Approximately 60% of ITRs and ncRNAs were more similar to nonfunctional sequences and were likely transcriptional noise. The predictive framework established here provides not only a comprehensive look at how functional, genic sequences are distinct from likely nonfunctional ones, but also a new way to differentiate novel genes from genomic regions with noisy transcriptional activities.


How Do Social Needs Cluster Among Low-Income Individuals?
Social needs screening in health care settings reveals that many low-income individuals have multiple unmet social needs at the same time. Having multiple simultaneous social needs greatly increases the odds of experiencing adverse health outcomes. To better understand how and which social needs cluster in these cases, the authors examined data from 14,749 low-income adults who completed a social needs assessment in one of 4 separate studies conducted between 2008 and 2019 in the United States. Participants were Medicaid beneficiaries, helpline callers, and daily smokers. Findings were strikingly consistent across the 4 studies. Participants with ≥2 social needs (n = 5621; 38% of total) experienced more stress, depressive symptoms, sleep problems, and chronic diseases and were more likely to rate their health as fair or poor. Social needs reflecting financial strain were highly correlated, such as needing help paying utility bills and needing money for necessities such as food, shelter, and clothing (r = .49 to .71 across studies). Participants experienced 351 distinct combinations of ≥2 social needs. The 10 most common combinations accounted for more than half of all participants with ≥2 needs. Clusters of social needs varied by subgroups. Women with children were more likely than others to need more space in their home and help paying utility bills; low-income men were more likely to be physically threatened and need a place to stay; older, sicker adults were more likely to need money for necessities and unexpected expenses, as well as transportation. Findings are discussed in the context of creating smarter, more efficient social needs interventions.


Experimental setup for the growth of solid crystals of inert gases for particle detection.
Low energy threshold detectors are necessary in many frontier fields of the experimental physics. In this work, we present a novel detection approach based on pure or doped matrices of inert gases solidified at cryogenic temperatures. The small energy release of the incident particle can be transferred directly (in pure crystals) or through a laser-driven ionization (in doped materials) to the electrons of the medium that are then converted into free electrons. The charge collection process of the electrons that consists in their drift within the crystal and their extraction through the solid-vacuum interface gives rise to an electric signal that we exploit for preliminary tests of charge collection and crystal quality. Such tests are carried out in different matrices of neon and methane using an UV-assisted apparatus for electron injection in crystals.


[Kidney transplantation with donors in heart block. Long-term results].
The shortage of renal grafts has led to the search for other alternatives. The use of grafts from non-heart-beating donors (NHBD) can increase the number of transplants 8% to 20%. Clinical studies conducted by different groups, have found that the long-term graft and patient survival are not different from those of recipients of kidneys from heart-beating donors (HBCD). The long-term results of a group of 52 recipients of NHBD kidneys were compared with those of 98 recipients of HBCD grafts. There were no differences in donor and recipient ages, HLA compatibility, reperfusion and cold ischemia times. There were no differences in the incidence of rejection episodes or non-functioning kidneys. Warm ischemia between 30 to 60 min or < 30 min did not influence the incidence of non-functioning kidneys. However, NHBD graft recipients had a higher incidence of acute tubular necrosis (67% versus 46%), recovers of renal function was slower, the duration of oliguria was longer and dialysis was required. The 8-year actuarial survival data were similar for both groups; 65% for the NHBD and 70% for the HBCD graft recipients. We can conclude that NHBDs are an important source of donor kidneys. The 12 points established by The First International Workshop on Non-Heart-Beating Donors which appear at the end of the present article are embodied in the Treaty of Maastricht regulations of organ transplantation from non-heart-beating donors.


Screening and Health Behaviors among Persons Diagnosed with Familial Adenomatous Polyposis and Their Relatives.
Familial Adenomatous Polyposis (FAP) is a rare autosomal dominantly inherited colorectal cancer syndrome. Individuals with FAP often undergo colectomy and are recommended to follow several surveillance protocols. Biological relatives of persons with FAP may also be at risk and thus should undergo genetic counseling. Screening adherence, genetic testing, and other health behaviors among individuals with FAP and their relatives are not well characterized. We conducted a cross-sectional self-report survey with individuals who have FAP (n = 35) and their biological relatives (n = 15). Respondents were recruited through a cancer center registry for inherited colon cancers. Most relatives had undergone colon cancer screening; 40% had undergone genetic testing. One fifth of respondents with FAP had not undergone an upper endoscopy, contrary to usual recommendations. Cigarette smoking rates were above average and were higher among FAP respondents. Use of vitamin supplements was fairly common, more so among those with FAP. Although most people had been screened, there are areas for improvement, notably for upper endoscopy among individuals with FAP and genetic testing among family members. Several other health-risk behaviors and health concerns other than FAP were identified. Further research into factors contributing to screening rates and other health behaviors in this high-risk population is warranted.


Numerical demonstration of neuromorphic computing with photonic crystal cavities.
We propose a new design for a passive photonic reservoir computer on a silicon photonics chip which can be used in the context of optical communication applications, and study it through detailed numerical simulations. The design consists of a photonic crystal cavity with a quarter-stadium shape, which is known to foster interesting mixing dynamics. These mixing properties turn out to be very useful for memory-dependent optical signal processing tasks, such as header recognition. The proposed, ultra-compact photonic crystal cavity exhibits a memory of up to 6 bits, while simultaneously accepting bitrates in a wide region of operation. Moreover, because of the inherent low losses in a high-Q photonic crystal cavity, the proposed design is very power efficient.


Cardiovascular Complications of Collagen Vascular Disease.
Collagen vascular diseases commonly affect the heart; cardiovascular events are the major cause of mortality in people with these diseases. A striking feature of the cardiac involvement in individuals with systemic lupus erythematosus (SLE) and rheumatoid arthritis is aggressive and accelerated atherosclerosis; women with SLE in the 35- to 44-year-old age group are more than 50 times more likely to suffer myocardial infarction than are matched controls. Traditional risk factors contribute to the accelerated atherosclerosis, but cannot explain the extent of risk. It is possible that the inflammatory process, which is similar to the inflammatory process in atherosclerosis, pays a critical pathophysiologic role. It is critically important to identify the presence of traditional cardiovascular risk factors (eg, tobacco usage, hypertension, hypercholesterolemia, diabetes, homocysteinemia), and to modify these to secondary prevention targets. Cardiac valvular disease is common in individuals with SLE and rheumatoid arthritis; its presence should be anticipated and subacute bacterial endocarditis prophylaxis precautions initiated. Cardiac autonomic neuropathy and conduction disturbances are common in people with heart disease related to systemic sclerosis and human leukocyte antigen B27; these patients should be monitored carefully for evidence of dysrhythmias.


Ultrasound measurement of subsynovial connective tissue thickness in the carpal tunnel: An intrarater/interrater reliability and agreement study.
Non-inflammatory thickening of the subsynovial connective tissue (SSCT) in the carpal tunnel is commonly found in subjects with carpal tunnel syndrome (CTS), and quantification may shed light on CTS pathogenesis. To date, information on the reliability of ultrasound quantification of SSCT is scarce. Therefore, we investigated intrarater and interrater reliability/agreement for ultrasound quantification of SSCT thickness in subjects with and without CTS, and predictors for tissue thickness. Two investigators quantified SSCT thickness and thickness ratio on ultrasound in 16 healthy subjects (age, 24-65 years; 16 left/14 right wrists) and 17 subjects with CTS (age, 37-83 years; 14 left/14 right wrists). Intra- and inter-rater reliability/agreement were assessed on intraclass correlation coefficients, standard error of measurement and minimal detectable change. A mixed-effects model was used to evaluate potential predictors for SSCT thickness. Intra- and inter-rater reliability analysis showed good to excellent intraclass correlation coefficients in both groups, ranging from 0.772 to 0.965. The maximum percentage standard error of measurement was 8%. The maximum minimal detectable change was 14% within raters, and 20% between raters. Both intra- and inter-rater reliability values for thickness ratio were poor. Presence of CTS (ß = 0.180; p = 0.015) correlated positively with SSCT thickness. Ultrasound is a reliable method for quantification of SSCT thickness, but not for thickness ratio. Presence of CTS correlates positively with SSCT thickness.


Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin.
The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a widely used anticoagulant drug, is structurally similar to HS and is a common experimental proxy. Exogenous heparin prevents infection by a range of viruses, including S-associated coronavirus isolate HSR1. Here, we show that heparin inhibits severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invasion of Vero cells by up to 80% at doses achievable through prophylaxis and, particularly relevant, within the range deliverable by nebulisation. Surface plasmon resonance and circular dichroism spectroscopy demonstrate that heparin and enoxaparin, a low-molecular-weight heparin which is a clinical anticoagulant, bind and induce a conformational change in the spike (S1) protein receptor-binding domain (S1 RBD) of SARS-CoV-2. A library of heparin derivatives and size-defined fragments were used to probe the structural basis of this interaction. Binding to the RBD is more strongly dependent on the presence of 2-O or 6-O sulfate groups than on N-sulfation and a hexasaccharide is the minimum size required for secondary structural changes to be induced in the RBD. It is likely that inhibition of viral infection arises from an overlap between the binding sites of heparin/HS on S1 RBD and that of the angiotensin-converting enzyme 2. The results suggest a route for the rapid development of a first-line therapeutic by repurposing heparin and its derivatives as antiviral agents against SARS-CoV-2 and other members of the Coronaviridae.


Theory and data for simulating fine-scale human movement in an urban environment.
Individual-based models of infectious disease transmission depend on accurate quantification of fine-scale patterns of human movement. Existing models of movement either pertain to overly coarse scales, simulate some aspects of movement but not others, or were designed specifically for populations in developed countries. Here, we propose a generalizable framework for simulating the locations that an individual visits, time allocation across those locations, and population-level variation therein. As a case study, we fit alternative models for each of five aspects of movement (number, distance from home and types of locations visited; frequency and duration of visits) to interview data from 157 residents of the city of Iquitos, Peru. Comparison of alternative models showed that location type and distance from home were significant determinants of the locations that individuals visited and how much time they spent there. We also found that for most locations, residents of two neighbourhoods displayed indistinguishable preferences for visiting locations at various distances, despite differing distributions of locations around those neighbourhoods. Finally, simulated patterns of time allocation matched the interview data in a number of ways, suggesting that our framework constitutes a sound basis for simulating fine-scale movement and for investigating factors that influence it.


A FimH inhibitor prevents acute bladder infection and treats chronic cystitis caused by multidrug-resistant uropathogenic Escherichia coli ST131.
Escherichia coli O25b:H4-ST131 represents a predominant clone of multidrug-resistant uropathogens currently circulating worldwide in hospitals and the community. Urinary tract infections (UTIs) caused by E. coli ST131 are typically associated with limited treatment options and are often recurrent. Using established mouse models of acute and chronic UTI, we mapped the pathogenic trajectory of the reference E. coli ST131 UTI isolate, strain EC958. We demonstrated that E. coli EC958 can invade bladder epithelial cells and form intracellular bacterial communities early during acute UTI. Moreover, E. coli EC958 persisted in the bladder and established chronic UTI. Prophylactic antibiotic administration failed to prevent E. coli EC958-mediated UTI. However, 1 oral dose of a small-molecular-weight compound that inhibits FimH, the type 1 fimbriae adhesin, significantly reduced bacterial colonization of the bladder and prevented acute UTI. Treatment of chronically infected mice with the same FimH inhibitor lowered their bladder bacterial burden by >1000-fold. In this study, we provide novel insight into the pathogenic mechanisms used by the globally disseminated E. coli ST131 clone during acute and chronic UTI and establish the potential of FimH inhibitors as an alternative treatment against multidrug-resistant E. coli.


Synthesis of saccharocin from apramycin and evaluation of its ribosomal selectivity.
We describe a straightforward synthesis of the apramycin biosynthetic precursor saccharocin from apramycin by regioselective partial azidation followed by stereoretentive oxidative deamination. Saccharocin was found to exhibit excellent selectivity for inhibition of the bacterial ribosome over the eukaryotic ribosomes indicating that its presence as a minor impurity in apramycin itself should not be problematic in the development of the latter as a clinical candidate.


The Prevalence of Depression among Untreated Obstructive Sleep Apnea Patients Using a Standardized Psychiatric Interview.
The aims of this study were: (1) to use a standardized psychiatric interview, conducted by a trained psychologist to assess the prevalence of depression among patients with untreated OSA, and (2) to identify if OSA severity or other comorbid disorders (insomnia, hypertension, and diabetes) are related to depression among patients with untreated OSA. Participants were newly diagnosed patients with OSA (n = 284) waiting to start positive airway pressure (PAP) treatment. The Mini International Neuropsychiatric Interview (MINI) was used to assess depression. Overall, 15.5% of the sample met the diagnosis for dysthymia. Women had a significantly higher prevalence (29.5% versus 11.7% among men, p < 0.001). The prevalence of major depression was 6% in the overall sample and there was no difference in the prevalence among sexes (5.8% among men versus 6.6 % among women). Obesity, daytime sleepiness, low physical activity, initial and late insomnia, low quality of life, and sleep medication and antidepressant use were all related to depression, whereas OSA severity, as measured by apnea-hypopnea index or oxygen desaturation index, was not. Daytime sleepiness, initial insomnia, and sleep medication use were the strongest predictors of depression in multivariable analyses. Sleep medication use, daytime sleepiness, and symptoms of initial insomnia were independently related to depression but OSA severity was not. Increased awareness of the relationship between depression and OSA and the appropriate use of assessment tools might substantially improve diagnostic accuracy as well as treatment outcome for both disorders.


A survey of the current clinical practice of psychiatrists and accident and emergency specialists in the United Kingdom concerning vitamin supplementation for chronic alcohol misusers.
Although it is well known that B-vitamin deficiencies directly affecting the brain are common in alcohol misuse, no concise guidelines on the use of vitamin supplements in alcohol misusers currently exist in the UK. The purpose of this study was to assess current practice and opinion among UK physicians. Questionnaires were completed by a total of 427 physicians comprising Accident and Emergency (A&E) specialists and psychiatrists, with a response rate of 25%. The main findings were that vitamin deficiency was perceived as being uncommon amongst alcohol misusers (<25%) and there was no consensus as to which B vitamins are beneficial in treatment or the best method of administration of B-vitamin supplementation. The majority of psychiatrists favoured oral administration for prophylaxis against the Wernicke-Korsakoff syndrome in chronic alcohol misusers and parenteral therapy in patients with signs of Wernicke-Korsakoff syndrome. Whilst only just over half the A&E specialists expressed a preference, most favoured parenteral therapy in both cases. Most respondents did not currently have a unit policy/protocol on the management of vitamin supplementation in chronic alcohol misusers. Overall, the findings suggest that there is wide variation in current practice and highlight the need for guidelines in this area.


Mathematical modeling in cancer nanomedicine: a review.
Cancer continues to be among the leading healthcare problems worldwide, and efforts continue not just to find better drugs, but also better drug delivery methods. The need for delivering cytotoxic agents selectively to cancerous cells, for improved safety and efficacy, has triggered the application of nanotechnology in medicine. This effort has provided drug delivery systems that can potentially revolutionize cancer treatment. Nanocarriers, due to their capacity for targeted drug delivery, can shift the balance of cytotoxicity from healthy to cancerous cells. The field of cancer nanomedicine has made significant progress, but challenges remain that impede its clinical translation. Several biophysical barriers to the transport of nanocarriers to the tumor exist, and a much deeper understanding of nano-bio interactions is necessary to change the status quo. Mathematical modeling has been instrumental in improving our understanding of the physicochemical and physiological underpinnings of nanomaterial behavior in biological systems. Here, we present a comprehensive review of literature on mathematical modeling works that have been and are being employed towards a better understanding of nano-bio interactions for improved tumor delivery efficacy.


Use of matched unrelated donors compared with matched related donors is associated with lower relapse and superior progression-free survival after reduced-intensity conditioning hematopoietic stem cell transplantation.
As success of reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) relies primarily on graft-versus-leukemia (GVL) activity, increased minor HLA disparity in unrelated compared to related donors could have a significant impact on transplant outcomes. To assess whether use of unrelated donors (URD) engenders more potent GVL in RIC HSCT compared to matched related donors (MRD), we retrospectively studied 433 consecutive T-replete 6/6 HLA matched URD (n = 246) and MRD (n = 187) RIC HSCT for hematologic malignancies at our institution. Diseases included: acute myelogenous leukemia (AML) (127), non-Hodgkin lymphoma (NHL) (71), chronic lymphocytic leukemia (CLL) (68), myelodysplastic syndrome (MDS) (64), Hodgkin disease (HD) (40), chronic myeloid leukemia (CML) (25), multiple myeloma (MM) (23), myeloproliferative disorder (MPD) (12), acute lymphoblastic leukemia (ALL) (7), and other leukemia (1). All received uniform fludarabine and intravenous busulfan conditioning, and GVHD prophylaxis with tacrolimus/mini-methroxate (mini-MTX) or tacrolimus/sirolimus ± mini-MTX. Unrelated donors were younger compared to MRD (median donor age: 33 years versus 52 years, P < .0001), and provided larger CD34(+) products (median CD34(+) cells infused: 8.7 × 10(6)/kg versus 7.5 × 10(6)/kg, P = .002). Distribution of diseases, disease risk, prior transplant, and cytomegalovirus (CMV) status was similar in both cohorts. Cumulative incidence of grade II-IV acute GVHD (at day +180), 2-year chronic GVHD, and 2-year nonrelapse mortality (NRM) were 20% versus 16%, 55% versus 50%, and 8% versus 6% in URD and MRD, respectively (P = NS). Cumulative incidence of relapse at 2 years was lower in URD, 52% versus 65% (P = .005). With median follow-up of 26.5 and 35.8 months, 2-year progression-free survival (PFS) was significantly better in unrelated donor transplants, 39.5% for URD, and 29% for MRD (P = .01). Overall survival (OS) at 2 years were 56% for URD versus 50% for MRD (P = .53). In multivariable analysis, URD was associated with a lower risk of relapse (hazard ratio [HR] 0.67, P = .002) and superior PFS (HR 0.69, P = .002). These results suggest that URD is associated with greater GVL activity than MRD, and could have practice changing impact on future donor selection in RIC HSCT.


Network inference performance complexity: a consequence of topological, experimental and algorithmic determinants.
Network inference algorithms aim to uncover key regulatory interactions governing cellular decision-making, disease progression and therapeutic interventions. Having an accurate blueprint of this regulation is essential for understanding and controlling cell behavior. However, the utility and impact of these approaches are limited because the ways in which various factors shape inference outcomes remain largely unknown. We identify and systematically evaluate determinants of performance-including network properties, experimental design choices and data processing-by developing new metrics that quantify confidence across algorithms in comparable terms. We conducted a multifactorial analysis that demonstrates how stimulus target, regulatory kinetics, induction and resolution dynamics, and noise differentially impact widely used algorithms in significant and previously unrecognized ways. The results show how even if high-quality data are paired with high-performing algorithms, inferred models are sometimes susceptible to giving misleading conclusions. Lastly, we validate these findings and the utility of the confidence metrics using realistic in silico gene regulatory networks. This new characterization approach provides a way to more rigorously interpret how algorithms infer regulation from biological datasets. Code is available at http://github.com/bagherilab/networkinference/. Supplementary data are available at Bioinformatics online.


A framework for distributed health professions training: using participatory action research to build consensus.
There is a global trend towards providing training for health professions students outside of tertiary academic complexes. In many countries, this shift places pressure on available sites and the resources at their disposal, specifically within the public health sector. Introducing an educational remit into a complex health system is challenging, requiring commitment from a range of stakeholders, including national authorities. To facilitate the effective implementation of distributed training, we developed a guiding framework through an extensive, national consultative process with a view to informing both practice and policy. We adopted a participatory action research approach over a four year period across three phases, which included seven local, provincial and national consultative workshops, reflective work sessions by the research team, and expert reviews. Approximately 240 people participated in these activities. Engagement with the national department of health and health professions council further informed the development of the Framework. Each successive 'feedback loop' contributed to the development of the Framework which comprised a set of guiding principles, as well as the components essential to the effective implementation of distributed training. Analysis further pointed to the centrality of relationships, while emphasising the importance of involving all sectors relevant to the training of health professionals. A tool to facilitate the implementation of the Framework was also developed, incorporating a set of 'Simple Rules for Effective distributed health professions training'. A national consensus statement was adopted. In this project, we drew on the thinking and practices of key stakeholders to enable a synthesis between their embodied and inscribed knowledge, and the prevailing literature, this with a view to further enaction as the knowledge generators become knowledge users. The Framework and its subsequent implementation has not only assisted us to apply the evidence to our educational practice, but also to begin to influence policy at a national level.


A CCR5-tropic simian-HIV molecular clone capable of inducing AIDS in rhesus macaques.
We previously reported the derivation of a CCR5 (R5)-tropic pathogenic strain SHIVSF162P3. Here, we show that a simian-HIV (SHIV) molecular clone expressing the entire env gp160 of SHIVSF162P3, termed SHIV P3gp160, could fully recapitulate the in vivo replicative characteristics of the parental isolate. SHIV P3gp160 is mucosally transmissible, preferentially depletes memory CD4 T cells, and induced simian AIDS in 2 of 6 infected macaques. The availability of an infectious R5 SHIV molecular clone that can be transmitted mucosally and causes disease provides an important reagent for studies of lentiviral pathogenesis and AIDS vaccine research.


Validation of a dysphagia screening tool in acute stroke patients.
Although many dysphagia screening tools exist, none has high sensitivity and reliability or can be administered quickly with minimal training. To design and validate a swallowing screening tool to be used by health care professionals who are not speech language pathologists to identify dysphagia and aspiration risk in acute stroke patients. In a prospective study of 300 patients admitted to the stroke service at an urban tertiary care hospital, interrater and test-retest reliabilities of a new tool (the Acute Stroke Dysphagia Screen) were established. The tool was administered by nursing staff when patients were admitted to the stroke unit. A speech language pathologist blinded to the results with the new tool administered the Mann Assessment of Swallowing Ability, a clinical bedside evaluation, with dysphagia operationally defined by a score less than 178. The mean time from admission to screening with the new tool was 8 hours. The mean time between administration of the new tool and the clinical bedside evaluation was 32 hours. For the new tool, interrater reliability was 93.6% and test-retest reliability was 92.5%. The new tool had a sensitivity of 91% and a specificity of 74% for detecting dysphagia and a sensitivity of 95% and a specificity of 68% for detecting aspiration risk. The Acute Stroke Dysphagia Screen is an easily administered and reliable tool that has sufficient sensitivity to detect both dysphagia and aspiration risk in acute stroke patients.


The influence of genetic background on the susceptibility of inbred mice to streptozotocin-induced diabetes.
Multiple low-dose injections of streptozotocin (STZ) induce a delayed but progressively increasing state of hyperglycemia in mice. Different inbred strains of mice show different susceptibility to this treatment. We examined whether genetic factors associated with the H-2 complex influence the susceptibility or resistance, using a selected group of 12 inbred and 5 congenic resistant strains of mice. We found that different congenic strains differed significantly in their susceptibility to STZ-induced diabetes, suggesting that H-2-associated genes do influence the susceptibility. However, at least some inbred strains sharing the same H-2 haplotype also differed in their susceptibility, indicating that genes outside the H-2 complex may also affect the susceptibility. Therefore, there appear to be at least two genes, one within and one or more outside the H-2 complex, that determine the susceptibility to multiple low doses of STZ.


Critical Review of Plant Cell Wall Matrix Polysaccharide Glycosyltransferase Activities Verified by Heterologous Protein Expression.
The life cycle and development of plants requires the biosynthesis, deposition, and degradation of cell wall matrix polysaccharides. The structures of the diverse cell wall matrix polysaccharides influence commercially important properties of plant cells, including growth, biomass recalcitrance, organ abscission, and the shelf life of fruits. This review is a comprehensive summary of the matrix polysaccharide glycosyltransferase (GT) activities that have been verified using in vitro assays following heterologous GT protein expression. Plant cell wall (PCW) biosynthetic GTs are primarily integral transmembrane proteins localized to the endoplasmic reticulum and Golgi of the plant secretory system. The low abundance of these enzymes in plant tissues makes them particularly difficult to purify from native plant membranes in quantities sufficient for enzymatic characterization, which is essential to study the functions of the different GTs. Numerous activities in the synthesis of the major cell wall matrix glycans, including pectins, xylans, xyloglucan, mannans, mixed-linkage glucans (MLGs), and arabinogalactan components of AGP proteoglycans have been mapped to specific genes and multi-gene families. Cell wall GTs include those that synthesize the polymer backbones, those that elongate side branches with extended glycosyl chains, and those that add single monosaccharide linkages onto polysaccharide backbones and/or side branches. Three main strategies have been used to identify genes encoding GTs that synthesize cell wall linkages: analysis of membrane fractions enriched for cell wall biosynthetic activities, mutational genetics approaches investigating cell wall compositional phenotypes, and omics-directed identification of putative GTs from sequenced plant genomes. Here we compare the heterologous expression systems used to produce, purify, and study the enzyme activities of PCW GTs, with an emphasis on the eukaryotic systems Nicotiana benthamiana, Pichia pastoris, and human embryonic kidney (HEK293) cells. We discuss the enzymatic properties of GTs including kinetic rates, the chain lengths of polysaccharide products, acceptor oligosaccharide preferences, elongation mechanisms for the synthesis of long-chain polymers, and the formation of GT complexes. Future directions in the study of matrix polysaccharide biosynthesis are proposed.


Seasonal variation in content, chemical composition and antimicrobial and cytotoxic activities of essential oils from four Mentha species.
The aim of the present study was to appraise variation in the chemical composition, and antimicrobial and cytotoxic activities of essential oils from the leaves of four Mentha species-M. arvensis, M. piperita, M. longifolia and M. spicata-as affected by harvesting season. Disc diffusion and broth microdilution susceptibility assays were used to evaluate the antimicrobial activity of Mentha essential oils against a panel of microorganisms. The cytotoxicity of essential oils was tested on breast cancer (MCF-7) and prostate cancer (LNCaP) cell lines using the MTT assay. The essential oil contents of M. arvensis, M. piperita, M. longifolia and M. spicata were 17.0, 12.2, 10.8 and 12.0 g kg(-1) from the summer and 9.20, 10.5, 7.00 and 9.50 g kg(-1) from the winter crops, respectively. Gas chromatographic-mass spectrometric analysis revealed that mostly quantitative rather than qualitative variation was observed in the oil composition of each species. The principal chemical constituents determined in M. arvensis, M. piperita, M. longifolia and M. spicata essential oils from both seasons were menthol, menthone, piperitenone oxide and carvone, respectively. The tested essential oils and their major components exhibited notable antimicrobial activity against most of the plant and human pathogens tested. The tested essential oils also exhibited good cytotoxicity potential. Of the Mentha essential oils tested, M. arvensis essential oil showed relatively better antimicrobial and cytotoxic activities. A significant variation in the content of most of the chemical components and biological activities of seasonally collected samples was documented.


ORAL ADMINISTRATION OF PENICILLIN.
A convenient, practical and effective procedure of administering penicillin by mouth consists of mixing the drug with one tablespoonful of aluminum hydroxide. Substantially higher blood levels are obtained following a 50,000 and a 100,000 unit dose of penicillin with this method than after administration of the drug dissolved in water, either with or without previous ingestion of a mild antacid, such as aluminum hydroxide. Adsorption of penicillin on aluminum hydroxide appears to exert a local protective effect against that portion of gastric acid with which it comes into contact.


Do the Eyes Have It? A Systematic Review on the Role of Eye Gaze in Infant Language Development.
Eye gaze is a ubiquitous cue in child-caregiver interactions, and infants are highly attentive to eye gaze from very early on. However, the question of why infants show gaze-sensitive behavior, and what role this sensitivity to gaze plays in their language development, is not yet well-understood. To gain a better understanding of the role of eye gaze in infants' language learning, we conducted a broad systematic review of the developmental literature for all studies that investigate the role of eye gaze in infants' language development. Across 77 peer-reviewed articles containing data from typically developing human infants (0-24 months) in the domain of language development, we identified two broad themes. The first tracked the effect of eye gaze on four developmental domains: (1) vocabulary development, (2) word-object mapping, (3) object processing, and (4) speech processing. Overall, there is considerable evidence that infants learn more about objects and are more likely to form word-object mappings in the presence of eye gaze cues, both of which are necessary for learning words. In addition, there is good evidence for longitudinal relationships between infants' gaze following abilities and later receptive and expressive vocabulary. However, many domains (e.g., speech processing) are understudied; further work is needed to decide whether gaze effects are specific to tasks, such as word-object mapping or whether they reflect a general learning enhancement mechanism. The second theme explored the reasons why eye gaze might be facilitative for learning, addressing the question of whether eye gaze is treated by infants as a specialized socio-cognitive cue. We concluded that the balance of evidence supports the idea that eye gaze facilitates infants' learning by enhancing their arousal, memory, and attentional capacities to a greater extent than other low-level attentional cues. However, as yet, there are too few studies that directly compare the effect of eye gaze cues and non-social, attentional cues for strong conclusions to be drawn. We also suggest that there might be a developmental effect, with eye gaze, over the course of the first 2 years of life, developing into a truly ostensive cue that enhances language learning across the board.


Indeterminate cell tumor of the spleen.
Indeterminate cell tumor is an extremely rare neoplasm that mainly occurs in the skin. We report a case of indeterminate cell tumor arising from the spleen, a previously unreported site for indeterminate cell tumor. Histologically, the tumor showed nests, nodules, and sheets of large polygonal cells with mostly oval nuclei; open chromatin; variable nucleoli; and abundant, eosinophilic cytoplasm. Some cells possessed irregularly convoluted nuclei with nuclear grooves and granular cytoplasm, suggestive of Langerhans cells. Immunohistochemically, the tumor cells were diffusely positive for S-100 and CD1a and negative for Langerin. No Birbeck granules were found by electron microscopy. Clinical and radiologic examination showed no other organomegaly or lymphadenopathy. A diagnosis of primary indeterminate cell tumor of the spleen was rendered. To the best of our knowledge, this is the first indeterminate cell tumor reported in the spleen. Biologic insights into dendritic cells in the spleen and the pertinent literature on these entities are reviewed.


Public health awareness of emerging zoonotic viruses of bats: a European perspective.
Bats classified in the order Chiroptera are the most abundant and widely distributed non-human mammalian species in the world. Several bat species are reservoir hosts of zoonotic viruses and therefore can be a public health hazard. Lyssaviruses of different genotypes have emerged from bats in America (Genotype 1 rabies virus; RABV), Europe (European bat lyssavirus; EBLV), and Australia (Australian bat lyssavirus; ABLV), whereas Nipah virus is the most important recent zoonosis of bat origin in Asia. Furthermore, some insectivorous bat species may be important reservoirs of SARS coronavirus, whereas Ebola virus has been detected in some megachiropteran fruit bats. Thus far, European bat lyssavirus (EBLV) is the only zoonotic virus that has been detected in bats in Europe. New zoonotic viruses may emerge from bat reservoirs and known ones may spread to a wider geographical range. To assess future threats posed by zoonotic viruses of bats, there is a need for accurate knowledge of the factors underlying disease emergence, for an effective surveillance programme, and for a rapid response system. In Europe, primary efforts should be focussed on the implementation of effective passive and active surveillance systems for EBLVs in the Serotine bat, Eptesicus serotinus, and Myotis species (i.e., M. daubentonii and M. dasycneme). Apart from that, detection methods for zoonotic viruses that may emerge from bats should be implemented. Analyses of data from surveillance studies can shed more light on the dynamics of bat viruses, (i.e., population persistence of viruses in bats). Subsequently, studies will have to be performed to assess the public health hazards of such viruses (i.e., infectivity and risk of infection to people). With the knowledge generated from this kind of research, a rapid response system can be set up to enhance public health awareness of emerging zoonotic viruses of bats.


Pseudo-fivefold symmetry in carbonyl process nickel.
Grains with pseudo-fivefold symmetry have been observed in nickel prepared by thermnal decomposition of nickel carbonyl. These grains were studied by transmission electron microscopy and electron diffraction Techniques. The defect structure and composite symmetry varied within a given sample, and the size of the grains varied with the thickness of the sample.


Laryngeal approach to the recurrent laryngeal nerve involved by thyroid cancer at the ligament of Berry.
Thyroid cancer often involves the RLN at the ligament of Berry, which makes preservation of the nerve difficult. If the portion of RLN is resected, finding the peripheral RLN for reconstruction is difficult. Here we describe a laryngeal approach performed before dissecting the RLN to overcome these problems. Between January 2007 and April 2011, 13 patients with papillary thyroid carcinoma had unilateral RLN involvement by the cancer at the ligament of Berry. Preoperatively, 8 had functioning vocal cords and 5 had unilateral paralysis. The laryngeal approach involves dividing the inferior pharyngeal constrictor muscle along the lateral edge of the thyroid cartilage and identifying the nerve under the muscle or behind the thyroid cartilage. This procedure was performed before resecting the tumor in 10 patients (Group 1) and after resection in the remaining 3 (Group 2). In Group 1, the RLN could be preserved with sharp dissection in 3 with functioning vocal cords preoperatively. Postoperatively they restored vocal cord function. The remaining 7 needed resection of the portion of RLN. RLN reconstruction was easily, since the peripheral RLN had already been identified. All patients in Group 2 needed resection of the portion of RLN. The peripheral RLN was identified in 2, and ansa-RLN anastomosis was performed. However, this was not possible in 1 patient. In patients with thyroid cancer involving the RLN at the ligament of Berry, performing the laryngeal approach before dissecting the nerve facilitates preservation or reconstruction of the nerve.


Risk of orthopedic surgical site infections in patients with rheumatoid arthritis treated with antitumor necrosis factor alfa therapy.
Introduction. International guidelines recommend interruption of anti-TNF medications in the perioperative period, but there are no randomized trials to support such recommendation. Objectives. To study literature evidence assessing the risk of surgical site infections in orthopedic surgery patients with RA using anti-TNF drugs, compared to untreated patients or those using conventional DMARD. Methods. Systematic review of cohort studies is concerning surgical site infections in orthopedic procedures in patients with RA. Results. Three studies were selected. Only one was considered of high-quality, albeit with low statistical power. The review resulted in inconclusive data, since the best quality study showed no significant differences between groups, while others showed increased risk of infections in patients using anti-TNF medications. Conclusion. It is unclear whether patients with RA using anti-TNF medications are at increased risk of surgical site infections. Randomized controlled trials or new high quality observational studies are needed to clarify the issue.


Diffuse scattering resulting from macromolecular frustration.
Distinctive diffuse scattering in the form of diffuse rings around Bragg positions has been observed in the diffraction patterns of a crystal of the N-terminal fragment of the Gag protein from Feline Foamy Virus. It is shown that these are caused by geometric frustration as molecules try to pack on the triangular b-c mesh of the space group P6(1)22. In order to explain the strong diffuse scattering it is necessary for the crystal to contain occupational disorder such that each unit cell contains one or other of two different molecular arrangements, A and B. The frustration arises because the nearest-neighbour packing prefers neighbouring cells to be AB or BA, which cannot be achieved on all three sides of a triangle simultaneously. To explain the observation that reciprocal sections hk5n, where n = integer, contain only Bragg peaks it is necessary that A and B are identical molecular arrangements differing only by a translation of 0.2c. The implications of the disorder for solving the structure of the protein by conventional techniques as well as the possibility of using the diffuse scattering for this purpose are discussed.


p53 and c-myc expression in stage A1 prostatic adenocarcinoma: useful prognostic determinants?
Forty-five stage A1 prostatic adenocarcinomas from patients with a mean age of 65 years were examined for p53 and c-myc expression to determine whether the presence or absence of these proteins could predict tumor behavior. Thirteen (6 of 45) and seventy-three percent (33 of 45) of cases were respectively p53 and c-myc positive. p53 expression was confirmed to the tumor cells, whereas c-myc immunoreactivity was present in both malignant and surrounding hyperplastic prostate. Statistical analysis showed that although p53 and c-myc expression were positively correlated, expression of neither nuclear protein was associated with a significantly worse survival (p53: p = 0.0791 exact two-tailed; c-myc: p = 0.738 exact two-tailed). These results suggest that while both p53 and c-myc may play a role in prostatic carcinogenesis, neither appears to identify patients who may benefit from treatment in stage A disease.


Minor salivary gland basal cell adenocarcinoma: a systematic review and report of a new case.
Basal cell adenocarcinoma (BCAC) of the minor salivary gland is an extremely rare disease: the most recent substantive literature review reports only 25 cases. Owing to the rarity of this disease, it has not yet been well characterized in the literature. We sought to expand the knowledge of minor salivary gland BCAC by performing an exhaustive literature review and adding to it a new case that is rare owing to the tumor's size, aggressive nature, and mixed histologic pattern. The review emphasizes epidemiologic patterns, diagnostic characteristics, treatment patterns, and expected prognosis for minor salivary gland BCAC. In June 2012, PubMed was queried using the term "salivary gland basal cell adenocarcinoma," and the resultant articles were reviewed. Those specifically mentioning a minor salivary gland BCAC were included in this study. Those that did not differentiate minor salivary gland BCAC from major salivary gland BCAC were excluded. The search was not limited by language and included articles from North America, Europe, Africa, and Asia from 1978 to June 2012. The PubMed search resulted in 195 articles, of which 33 articles reported at least 1 case of minor salivary gland BCAC. We report herein 72 cases of minor salivary gland BCAC (71 cases from the literature review and 1 new case reported herein). The mean patient age at the time of presentation was 56 years (range, 24-90 years), and the disease showed no sex predilection. The most common location was the palate, and the average lesions size was 2.4 cm (range, 0.7-4.2 cm). The treatment modality of choice was wide local excision (n = 57; 79%). There was a high local recurrence rate (n = 30; 41%) but a low rate of distant metastasis (n = 8; 11%). We present a comprehensive review of minor salivary gland BCAC, describing nearly 3 times as many cases as has been previously reported. This review characterizes a rare disease and increases awareness of the disease among otolaryngologists. Minor salivary gland BCAC is similar to major salivary gland BCAC and minor salivary gland tumors in general with regard to patient age, sex, tumor site, treatment modality, recurrence, metastasis, and mortality.


Expression of tenocyte lineage-related factors in regenerated tissue at sites of tendon defect.
The healing mechanism of ruptured or injured tendons is poorly understood. To date, some lineage-specific factors, such as scleraxis and tenomodulin, have been reported as markers of tenocyte differentiation. Because few studies have focused on tenocyte lineage-related factors with respect to the repaired tissue of healing tendons, the aim of this study was to investigate their expression during the tendon healing process. Defects were created in the patellar tendons of rats, and the patellae and patellar tendons were harvested at 3 days and at 1, 2, 3, 6, 12, and 20 weeks after surgery. They were studied using micro-computed tomography, and paraffin-embedded sections were then prepared for histological evaluation. Reverse transcription-polymerase chain reactions were performed to analyze the expression of genes related to the tenocyte lineage, chondrogenesis, and ossification. Repaired tissue became increasingly fibrous over time and contained a greater number of vessels than normal tendons, even in the later period. Safranin O staining revealed the existence of proteoglycan at 1 week and its persistence through 20 weeks. Ossification was detected in all tendons at 12 weeks. The expression of tenocyte lineage-related genes was high at 1 and 2 weeks. Chondrogenic genes were up-regulated until 6 weeks. Runt-related transcription factor 2, an osteogenic gene, was up-regulated at 20 weeks. In our tendon defect model, cells participating in the tendon healing process appeared to differentiate toward tenocyte lineage only in the early phase, and chondrogenesis seemed to occur from the early phase onward. To improve tendon repair, it will be necessary to promote and maintain tenogenesis and to inhibit chondrogenesis, especially in the early phase, in order to avoid erroneous differentiation of stem cells.


Epididymal changes associated with cryptorchidism in rats.
To investigate the effect of a new mechanically induced cryptorchidism model on rat epididymal histology. Eighteen 21-day-old Sprague Dawley rats were randomly divided into 3 groups of 6 animals each. Animals of Groups 1 and 2 were made unilaterally cryptorchid by closing the left inguinal canal, while Group 3 (controls), sham operated. At Day 60 (Group 1) and Day 90 (Group 2 and 3), the rats were sacrificed. The epididymides of both sides were weighed, and the diameter of the epididymal tubules, the height of the tubular epithelium and the presence of fibrosis of the caput epididymides were examined under a light-microscope. The cryptorchid epididymis had a significantly lower weight increase than the contralateral ones and the controls, but the epithelial height and diameter of caput epididymal tubules were not significantly different. Fibrosis was not observed. The authors proposed that this new model is a convenient method to evaluate the epididymal changes associated with experimental cryptorchidism.


Comparison of Serial Blood Collection by Facial Vein and Retrobulbar Methods in C57BL/6 Mice.
Many biomedical research protocols for mouse models involve serial blood collection and analysis. Two common techniques for serial blood collection in this species are the retrobulbar (RB, also called retroorbital) and facial vein (FV) methods. However, previous studies comparing these methods typically evaluated collection at a maximum of 2 time points. Here we compared hematologic values, adverse clinical effects, and histopathologic lesions in mice bled either once or serially (6 times) by using the FV or RB method. Mice (n = 48) were divided into 4 groups: single FV, single RB, serial FV and serial RB. Mice in the single-collection groups underwent a single blood collection by the indicated method, whereas those in the serial-collection groups were sampled once weekly for 6 consecutive weeks. All animals were euthanized and necropsied 2 wk after their last blood collection. Compared with all other groups, the serial FV group experienced more serious clinical adverse events, including 33% mortality, convulsions, head tilt, and hemorrhage from the ear canal and nares. In addition, mice in the FV groups had a significantly greater acute body weight loss compared with mice in the RB groups. Histologically, mice in both serial-collection groups had an increased incidence of tissue lesions compared with their respective single-collection groups. Importantly, only mice in the serial FV group had life-threatening histopathologic lesions, including cerebral hemorrhage or ischemia. Given these data, we conclude that serial blood collection in mice causes increased incidence of tissue damage compared with single sampling, and serial blood collection by the FV method causes substantial morbidity and mortality compared with the RB method.


Photosynthesis and drought: can we make metabolic connections from available data?
Photosynthesis is one of the key processes to be affected by water deficits, via decreased CO2 diffusion to the chloroplast and metabolic constraints. The relative impact of those limitations varies with the intensity of the stress, the occurrence (or not) of superimposed stresses, and the species we are dealing with. Total plant carbon uptake is further reduced due to the concomitant or even earlier inhibition of growth. Leaf carbohydrate status, altered directly by water deficits or indirectly (via decreased growth), acts as a metabolic signal although its role is not totally clear. Other relevant signals acting under water deficits comprise: abscisic acid (ABA), with an impact on stomatal aperture and the regulation at the transcription level of a large number of genes related to plant stress response; other hormones that act either concurrently (brassinosteroids, jasmonates, and salycilic acid) or antagonistically (auxin, cytokinin, or ethylene) with ABA; and redox control of the energy balance of photosynthetic cells deprived of CO2 by stomatal closure. In an attempt to systematize current knowledge on the complex network of interactions and regulation of photosynthesis in plants subjected to water deficits, a meta-analysis has been performed covering >450 papers published in the last 15 years. This analysis shows the interplay of sugars, reactive oxygen species (ROS), and hormones with photosynthetic responses to drought, involving many metabolic events. However, more significantly it highlights (i) how fragmented and often non-comparable the results are and (ii) how hard it is to relate molecular events to plant physiological status, namely photosynthetic activity, and to stress intensity. Indeed, the same data set usually does not integrate these different levels of analysis. Considering these limitations, it was hard to find a general trend, particularly concerning molecular responses to drought, with the exception of the genes ABI1 and ABI3. These genes, irrespective of the stress type (acute versus chronic) and intensity, show a similar response to water shortage in the two plant systems analysed (Arabidopsis and barley). Both are associated with ABA-mediated metabolic responses to stress and the regulation of stomatal aperture. Under drought, ABI1 transcription is up-regulated while ABI3 is usually down-regulated. Recently ABI3 has been hypothesized to be essential for successful drought recovery.