Auraptene/Naringin-Rich Fruit Juice of Citrus kawachiensis (Kawachi Bankan) Prevents Ischemia-Induced Neuronal Cell Death in Mouse Brain through Anti-Inflammatory Responses.
Cerebral ischemia/reperfusion leads to delayed neuronal cell death, resulting in brain damage. Auraptene (AUR) and naringin (NGIN), which exert neuroprotective effects in ischemic brain, are abundant in the peel of Citrus kawachiensis. Although parts of AUR/NGIN are transited from the peel to the juice during the squeezing of this fruit, these amounts in juice might be too low to exert effects. We thus prepared the AUR/NGIN-rich fruit juice of C. kawachiensis by addition of peel paste to the raw juice. The present study revealed that orally administration of the dried powder of this AUR/NGIN-rich fruit juice (2.5 g/kg/d) for 7 d to ischemic mice significantly suppressed the ischemia-induced neuronal cell death in the hippocampus, which was coincidently with the reduction of hyperactivation of microglia and astrocytes. These results suggest that AUR/NGIN-rich juice of C. kawachiensis may possess therapeutic potential for the prevention of neurodegenerative diseases via inhibition of inflammatory processes.


Prothrombin Complex Concentrate for Intracerebral Hemorrhage Secondary to Vitamin K Deficiency Bleeding in a 6-Week-Old Child.
Four-factor prothrombin complex concentrate is approved for use of life-threatening bleeding secondary to vitamin K antagonism in adults. We describe the use of four-factor prothrombin complex concentrate for hemostasis in a 6-week-old child with life-threatening vitamin K dependent-bleeding who never received vitamin K prophylaxis at birth.


[An optimized filter band analyzer for quantification of localized muscle fatigue].
A filter bank analyzer is described which determines the central frequency of the electromyographic signal as a characteristic value and exhibits it continuously. In contrast with previous methods, this analyzer needs only a narrow frequency band and few filters to obtain exact quantitative results. The filter bank parameters are determined by adapting them to the amplitude spectra of electromyograms during fatiguing dynamic muscle work. Six parallel band-pass filters transmit the expected average spectral function, with minimized differences in the frequency range from 18 Hz to 140 Hz. The systematic error of the center frequency amounts to less than 0.5%, when using precision filters with high roll-off. An example compares the shift of center frequency method with the fatigue index of myoelectrical activity.


Isolation and characterization of multiple hamster hemoglobins.
Multiple hemoglobins were found in the peripheral blood of hamsters when separated by analytical isoelectric focusing in polyacrylamide gel between pH 6.0 and pH 8.0. Five of these hemoglobins (I-V) were present in sufficient quantities for isolation by preparative isoelectric focusing and subsequent characterization. Cellulose acetate electrophoresis of the isolated hemoglobins resulted in producing as many as six different globin chains. The five hemoglobins were further characterized by their amino acid composition, N-terminal amino acid residue, and molecular weight.


Characterization of C-, J- and V-region-genes of the feline T-cell receptor gamma.
Lymphomas and leukemias are important neoplasias of domestic cats and human beings. In some cases it can be difficult to differentiate these tumors from reactive lymphatic hyperplasia. To overcome this problem, the diagnosis of lymphomas and leukemias in man is often supported by molecular techniques. To be able to establish such a technique in the cat we had to sequence the genes coding for the antigen receptors. As primary target in this study we choose the T-cell receptor gamma. Using 5'-and 3'-RACE techniques we were able to clone and sequence four different V-region genes, which can be clustered into two subgroups as well as six variants of the C-region gene. Additionally, we found eight J-region genes which can be classified into three subgroups. One of the V-region genes, six of the J-region genes and all C-region genes had not been described previously. All together we analysed 112 clones containing V- and J-region genes and 31 clones containing C-region genes. Sixty-six of these clones were full length containing the L-region as well as the 5'-UTR of the feline T-cell receptor gamma. The sequences of the V-region- and J-region-genes show sufficiently homologous areas that can be used to establish a small number of consensus-primers to be applied in molecular diagnosis of feline lymphomas and leukemias.


The significance of right ear auditory processing to balance.
Although the association between balance and hearing thresholds at different frequencies in the right/left ear is crucial, it has received scant empirical attention. Balance is widely ignored when evaluating hearing in adults. This study examined the relative contribution of left versus right ear hearing at different frequencies to balance, and the mediating role of suprathreshold speech perception on age-balance associations. Pure tone hearing thresholds (500-4000 Hz), suprathreshold speech perception, balance, and risk of falling were evaluated in 295 adults. The results indicate that the right ear contributes more to balance than the left ear. This might imply dominance of the left hemisphere in processing hearing cues for balance. Frequencies within the speech range (500/1000/2000 Hz) were correlated with balance and mediated the interaction between age and balance. These results should be considered when tailoring hearing and balance rehabilitation programs.


Use of polyvinylpyrrolidone-iodine solution for sterilisation and preservation improves mechanical properties and osteogenesis of allografts.
Allografts eliminate the disadvantages associated with autografts and synthetic scaffolds but are associated with a disease-transmission risk. Therefore, allograft sterilisation is crucial. We aimed to determine whether polyvinylpyrrolidone-iodine (PVP-I) can be used for sterilisation and as a new wet-preservation method. PVP-I-sterilised and preserved allografts demonstrated improved mechanical property, osteogenesis, and excellent microbial inhibition. A thigh muscle pouch model of nude mice showed that PVP-I-preserved allografts demonstrated better ectopic formation than Co60-sterilised allografts (control) in vivo (P < 0.05). Furthermore, the PVP-I-preserved group showed no difference between 24 h and 12 weeks of allograft preservation (P > 0.05). PVP-I-preserved allografts showed more hydrophilic surfaces and PVP-I-sterilised tendons showed higher mechanical strength than Co60-sterilised tendons (P < 0.05). The level of residual PVP-I was higher without washing and with prolonged preservation (P < 0.05). In vitro cellular tests showed that appropriate PVP-I concentration was nontoxic to preosteoblast cells, and cellular differentiation measured by alkaline phosphatase activity and osteogenic gene markers was enhanced (P < 0.05). Therefore, the improved biological performance of implanted allografts may be attributable to better surface properties and residual PVP-I, and PVP-I immersion can be a simple, easy method for allograft sterilisation and preservation.


Case of tetralogy of Fallot associated with hypoplasia of the right pulmonary artery. The right internal mammary artery as an aortopulmonary collateral artery in tetralogy of Fallot.
A three-month-old girl was referred to pediatric cardiology unit for evaluation of mild cyanosis and murmur. Chest roentgenogram revealed a boot-shaped heart. Echocardiography demonstrated subaortic ventricular septal defect, aortic override and infundibular stenosis. Then, the patient diagnosed as tetralogy of Fallot (TOF). Cardiac catheterization and angiocardiography revealed infundibular narrowing, hypoplasia of the right pulmonary artery and the enlarged right internal mammary artery originating from the right subclavian artery supplied blood flow into the right lung. The patient was performed complete repair. Post-operative period was uneventful. This is the first report presented about a case which pulmonary blood flow is provided by the enlarged right internal mammary artery in TOF associated with hypoplasia of the right pulmonary artery.


Understanding the relationship between type 2 diabetes and depression: lessons from genetically informative study designs.
To conduct a systematic review in order to comprehensively synthesize the findings from a diverse range of genetically informative studies on comorbid depression and type 2 diabetes. Database searches (1 January 2008 to 1 June 2020) in PubMed and EMBASE were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Eligible reports employed any type of genetically informed design, including twin modelling, Mendelian randomization, genome-wide association studies, polygenetic risk scores, or linkage disequilibrium score regression. Searches generated 451 unique citations, and 16 manuscripts met the inclusion criteria. The included studies addressed three aetiological models of the depression-diabetes relationship: uni- or bi-directional phenotypic causation; shared genetic liability; or gene-environment interaction. From these studies, there is modest evidence that type 2 diabetes is causally related to risk of developing depression, but much more limited evidence that depression is causally related to risk of diabetes. There is little evidence of shared genetic liability between depression and diabetes or of gene-environment interaction. Findings from genetically informed studies are mixed but provide some support for the uni- or bi-directional phenotypic model of depression and type 2 diabetes. Future studies should also explore the hypothesis that this relationship may be influenced by shared environmental risk factors. Findings can inform multifaceted approaches to diabetes prevention and care that reflect how psychosocial factors contribute to type 2 diabetes risk and outcomes.


Aza-BODIPY Probe-Decorated Mesoporous Black TiO2 Nanoplatform for the Highly Efficient Synergistic Phototherapy.
As an important noninvasive tumor treatment method, phototherapy has drawn extensive research interest. However, the requirements of separate excitation wavelengths, high degree of electron-hole recombination, and low reactive oxygen species (ROS) production capability are still the major barriers. This work reports the construction of a novel nanoplatform: design and synthesis of an aza-BODIPY (AB) probe-decorated mesoporous black titanium dioxide (TiO2) (MT) nanoparticles (NPs) for enhanced photodynamic therapy and photothermal therapy under single-wavelength near-infrared (NIR) laser irradiation for the first time. AB probe-decorated MT NPs (abbreviated as MTAB) were synthesized through the Al reduction of mesoporous anatase TiO2 NPs and subsequent adsorption of the AB probe. The mesoporous structure of MT ensured AB loading capacity and avoided the complicated modification and synthesis processes. Heterogeneous MTAB, which possessed staggered energy levels, were assessed for their capability for effective separation of photogenerated electrons and holes for the first time. Upon NIR laser light irradiation, MTAB exhibited sufficient ROS generation, resulting in distinct tumor cell killing and tumor tissue elimination. This unique heterogeneous nanoplatform with staggered energy levels provides a new strategy to enhance ROS generation and improve the therapeutic efficacy.


The optimal alternative for quantifying reference evapotranspiration in climatic sub-regions of Bangladesh.
Reference evapotranspiration (ETo) is a basic element for hydrological designing and agricultural water resources management. The FAO56 recommended Penman-Monteith (FAO56-PM) formula recognized worldwide as the robust and standard model for calculating ETo. However, the use of the FAO56-PM model is restricted in some data-scarce regions like Bangladesh. Therefore, it is imperative to find an optimal alternative for estimating ETo against FAO56-PM model. This study comprehensively compared the performance of 13 empirical models (Hargreaves-Samani, HargreavesM1, Hargreaves M2, Berti, WMO, Abtew, Irmak 1, Irmak 2, Makkink, Priestley-Taylor, Jensen-Haise, Tabari and Turc) by using statistical criteria for 38-years dataset from 1980 to 2017 in Bangladesh. The radiation-based model proposed by Abtew (ETo,6) was selected as an optimal alternative in all the sub-regions and whole Bangladesh against FAO56-PM model owing to its high accuracy, reliability in outlining substantial spatiotemporal variations of ETo, with very well linearly correlation with the FAO56-PM and the least errors. The importance degree analysis of 13 models based on the random forest (RF) also depicted that Abtew (ETo,6) is the most reliable and robust model for ETo computation in different sub-regions. Validation of the optimal alternative produced the largest correlation coefficient of 0.989 between ETo,s and ETo,6 and confirmed that Abtew (ETo,6) is the best suitable method for ETo calculation in Bangladesh.


ECG signal classification with binarized convolutional neural network.
Arrhythmias are a group of common conditions associated with irregular heart rhythms. Some of these conditions, for instance, atrial fibrillation (AF), might develop into serious syndromes if not treated in time. Therefore, for high-risk patients, early detection of arrhythmias is crucial. In this study, we propose employing deep convolutional neural network (CNN)-based algorithms for real-time arrhythmia detection. We first build a full-precision deep convolutional network model. With our proposed construction, we are able to achieve state-of-the-art level performance on the PhysioNet/CinC AF Classification Challenge 2017 dataset with our full-precision model. It is desirable to employ models with low computing resource requirements. It has been shown that a binarized model requires much less computing power and memory space than a full-precision model. We proceed to verify the feasibility of binarization in our neural network model. Network binarization can cause significant model performance degradation. Therefore, we propose employing a full-precision model as the teacher to regularize the training of the binarized model through knowledge distillation. With our proposed approach, we observe that network binarization only causes a small performance loss (the F1 score decreases from 0.88 to 0.87 for the validation set). Given that binarized convolutional networks can achieve favorable model performance while dramatically reducing computing cost, they are ideal for deployment on long-term cardiac condition monitoring devices. (Source code is available at https://github.com/yangfansun/bnn-ecg).


Relationship among cardiac index, inspiration/expiration ratio, and perfluorocarbon dose during partial liquid ventilation in an oleic acid model of acute lung injury in sheep.
The aim of this study was to demonstrate the influence of different inspiration/expiration (I/E) ratios on cardiac index (CI) and hemodynamics during partial liquid ventilation (PLV) using a large animal model of acute respiratory failure in a prospective, randomized controlled animal laboratory trial. After induction of respiratory failure by right atrial injection of 0.09 mL/kg oleic acid, (1) determination of agreement between reversed Fick and pulmonary artery thermodilution (QTD) techniques with progressive doses of perflubron (LiquiVent, Alliance Pharmaceutical Corp, San Diego, Calif) (n = 7 sheep) and (2) comparison of 4 groups with I/E ratios of 3.4:1, 2:1, 1:1, and 1:2 were performed, applying identical ventilatory patterns in all I/E groups (n = 28 sheep). PLV was established with intratracheal instillation of 25 mL/kg perflubron. Cardiac index was assessed at 15-minute intervals for a 120-minute experimental period by QTD. During progressive doses of PLV, the correlation (r) between Fick and QTD techniques was 0.82. Thermodilution deteriorated after induction of lung injury and recovered after PLV start. Regarding QTD, no significant changes after PLV onset (within-group comparison) and between I/E groups were observed (P < .05). The QTD technique is a satisfactory reflector of CI during PLV, and I/E ratio has no significant influence on CI, even using extreme inverse ratio ventilation.


Conformation and ion binding properties of peptides related to calcium binding domain III of bovine brain calmodulin.
The conformational and ion binding properties of the sequences 93-104, 96-104, and 93-98 of domain III of bovine brain calmodulin (CaM) have been studied by CD and Tb3+-mediated fluorescence. In aqueous solution the interaction of all fragments with Ca2+ and Mg2+ ions is very weak and without any effect on the peptide conformation, which remains always random. In trifluoroethanol the interaction is very strong and the different fragments exhibit very distinct binding properties. In particular, the dodecapeptide fragment 93-104, and its N-terminal hexapeptide 98-104, bind calcium and magnesium with a very high binding constant (Kb greater than 10(5) M-1), undergoing a substantial conformational change. The structural rearrangement is particularly evident in the hexapeptide fragment, which tend to form a beta-bend. The C-terminal nonapeptide fragment 96-104 interacts with calcium and magnesium more weakly, and the binding process causes a decrease of ordered structure. These results suggest that, even in the entire dodecapeptide sequence corresponding to the loop of domain III of CaM, the calcium binding site is shifted toward the N-terminal hexapeptide segment. This interpretation is consistent with the results of crystallographic studies of CaM, which show that the calcium ions are located toward the amino terminal portion of the loop.


Binding site of MraZ transcription factor in Mollicutes.
Mollicutes (mycoplasmas) feature a significant loss of known regulators of gene expression. Here, we identified the recognition site of the MraZ-family regulator of Mycoplasma gallisepticum, which is conserved in many species of different clades within class Mollicutes. The MraZ binding site is AAAGTG[T/G], in the promoter of mraZ gene it forms a series of direct repeats with a structure (AAAGTG[T/G]N3)k, where k = 3 most frequently. MraZ binds to a single repeat as an octamer complex. MraZ can also bind a single binding site or a series of repeats with different spacer lengths (2-4 nt); thus, it may play a role in the regulation of multiple operons in Mollicutes. In M. gallisepticum, MraZ acts as a transcriptional activator. The overexpression of MraZ leads to moderate filamentation of cells and the formation of aggregates, likely as a result of incomplete cytokinesis.


Combination therapy for dendritic keratitis with human leukocyte interferon and acyclovir.
We treated 45 patients with virologically verified dendritic keratitis with a combination of interferon and acyclovir 3% or with placebo and acyclovir 3% in a double-masked study. One drop of human leukocyte interferon (30 X 10(6) IU/ml) or albumin-placebo was administered daily. Acyclovir ointment was applied five times daily. The mean healing time of the corneal ulcers in 24 patients treated with interferon and acyclovir was 3.9 days and the mean healing time in 21 patients treated with placebo and acyclovir was seven days. The difference was significant (P less than .001).


AutoEER: automatic EEG-based emotion recognition with neural architecture search.
Objective.Emotion recognition based on electroencephalography (EEG) is garnering increasing attention among researchers due to its wide-ranging applications and the rise of portable devices. Deep learning-based models have demonstrated impressive progress in EEG-based emotion recognition, thanks to their exceptional feature extraction capabilities. However, the manual design of deep networks is time-consuming and labour-intensive. Moreover, the inherent variability of EEG signals necessitates extensive customization of models, exacerbating these challenges. Neural architecture search (NAS) methods can alleviate the need for excessive manual involvement by automatically discovering the optimal network structure for EEG-based emotion recognition.Approach.In this regard, we propose AutoEER (AutomaticEEG-basedEmotionRecognition), a framework that leverages tailored NAS to automatically discover the optimal network structure for EEG-based emotion recognition. We carefully design a customized search space specifically for EEG signals, incorporating operators that effectively capture both temporal and spatial properties of EEG. Additionally, we employ a novel parameterization strategy to derive the optimal network structure from the proposed search space.Main results.Extensive experimentation on emotion classification tasks using two benchmark datasets, DEAP and SEED, has demonstrated that AutoEER outperforms state-of-the-art manual deep and NAS models. Specifically, compared to the optimal model WangNAS on the accuracy (ACC) metric, AutoEER improves its average accuracy on all datasets by 0.93%. Similarly, compared to the optimal model LiNAS on the F1 Ssore (F1) metric, AutoEER improves its average F1 score on all datasets by 4.51%. Furthermore, the architectures generated by AutoEER exhibit superior transferability compared to alternative methods.Significance.AutoEER represents a novel approach to EEG analysis, utilizing a specialized search space to design models tailored to individual subjects. This approach significantly reduces the labour and time costs associated with manual model construction in EEG research, holding great promise for advancing the field and streamlining research practices.


Contamination assessment and health risk of arsenic exposure to stairway dust in the zinc smelting district, Northeast China.
Stairway dust samples were collected from residential communities in Huludao city to investigate population health risk of arsenic (As) exposure through stairway dust. ArcGIS software was used to analyze As spatial distribution in Huludao city. Hazard index was applied to assess health risk due to exposure to As in stairway dust. The results were that As concentrations ranged from 13.26 to 237.58 mg kg-1, and the mean value was 59.64 mg kg-1, which was seven times as high as the background value of Liaoning Province. The pattern of spatial distribution was concentric rings as the center of Huludao zinc plant, with the extension to the northeast and southwest. The average value of Igeo was 2.176, which fell into moderately polluted level. For non-carcinogenic risk, the hazard indexes were less than 1, indicating that there was almost no health risk for residents exposed to stairway dust. But population risk exposure to dust would increase rapidly with exposure time in stairway. The highest contribution to the overall figure of non-carcinogenic risk and carcinogenic risk appeared to be ingestion of substrate particles followed by inhalation pathway and dermal absorption of As in dust samples. And for carcinogenic risk, the risk values were lower than the threshold range of EPA's safe limits (1 × 10-6 and 1 × 10-4), suggesting that potential cancer risk of As due to exposure to stairway dust can be acceptable.


Increased alcohol self-administration following repeated Toll-like receptor 3 agonist treatment in male and female rats.
Toll-like receptor (TLR) signaling may play an important role in the neuroimmune system's involvement in the development and maintenance of alcohol use disorder (AUD). In the present study we administered the TLR3 agonist poly(I:C) in male and female Long-Evans rats to determine whether TLR3 agonism can increase alcohol consumption on a daily 15% alcohol operant self-administration paradigm. We found few effects when poly(I:C) was given every-other-day at 0.3 or 1.0 mg/kg. However, when 1.0 mg/kg was given on consecutive days, alcohol intake increased in the days following injections specifically in females. In a second experiment, we found that this effect only emerged when rats had a history of multiple poly(I:C) injections. In the final experiment the poly(I:C) dose was increased to 3.0 mg/kg on consecutive days which resulted in significant reductions in alcohol intake on injection days in females that were not accompanied by subsequent increases. The poly(I:C) dose was increased to 9.0 mg/kg for one final pair of injections which led to reductions in intake in both males and females followed by a male specific delayed increase in alcohol intake. Overall, repeated poly(I:C) administration was able to increase subsequent alcohol consumption in both sexes, with females showing an increase at a lower dose than males. These findings support TLR3 agonism in contributing to increased alcohol consumption and add to the body of work identifying the neuroimmune system as a potential therapeutic target for AUD.


Glucose levels affect LL-37 expression in monocyte-derived macrophages altering the Mycobacterium tuberculosis intracellular growth control.
Diabetes mellitus (DM)-2 patients have an increased susceptibility to develop pulmonary tuberculosis; this is partly due to the impairment of the innate immunity because of their higher glucose concentrations. In the present study, we determined the effect of the glucose concentrations in the LL-37 expression in infected and non-infected macrophages. Our results showed that the increasing glucose concentrations correlates with the low cathelicidin expression in non-infected cells, however in Mycobacterium tuberculosis infected cells, LL-37 expression was substantially increased in higher glucose concentrations, nevertheless the mycobacterial burden also increased, this phenomena can be associated with the cathelicidin immunomodulatory activity. Further evaluation for LL-37 needs to be done to determine whether this peptide can be used as a biomarker of tuberculosis progression in DM2 patients.


Evaluation of reproductive and developmental toxicities of Pu-erh black tea (Camellia sinensis var. assamica) extract in Sprague Dawley rats.
Pu-erh black tea, which is obtained by first parching crude green tea leaves and followed by secondary fermentation with microorganisms, has been believed to be beneficial beverages for health in PR China. But its potential toxicity when administered at a high dose as concentrated extract has not been completely investigated. The present study was aimed at evaluating potential reproductive and developmental toxicities of Pu-erh black tea extract (BTE) in Sprague Dawley rats. Growing rats were given BTE by gavage at levels of 0, 200, 700 and 2500mg/kg/day as the F0 generation in reproductive toxicity study. Additionally, BTE was administered to mate female rats from gestation day 0.5 through 19.5 at the doses of 0, 200, 700 and 2500mg/kg/day to evaluate the developmental toxicity. In the reproductive toxicity study, only 2500mg/kg/day BTE reduced the body weight gain and altered the relative organ weights including testes, prostata and ovary both for F0 parents and F1 offspring compared to the controls. High dose of BTE (2500mg/kg/day) administration caused developmental disturbances in embryo-to-foetus period including resorbed embryos, decreased embryo size and skeletal anomalies. In conclusion, the no-observed-adverse-effect level of BTE is 700mg/kg/day both for reproductive toxicity and developmental toxicities.


Influence of labor and oxytocin on in vitro leukotriene release by human fetal membranes and uterine decidua at term gestation.
The purpose of this study was to determine whether labor and oxytocin influence in vitro leukotriene release by human fetal membranes and uterine decidua at term gestation. All women (N = 21) were studied in an academic clinical research environment. They were delivered either vaginally or before labor by cesarean section. Tissues were incubated with calcium ionophore A23187 alone or with calcium ionophore A23187 after preincubation with either oxytocin, BW755c, or cycloheximide. Leukotrienes in culture medium were determined by high-performance liquid chromatography. Statistical analysis was performed with analysis of variance. Tissues obtained after vaginal delivery released significantly higher (p less than 0.05) quantities of leukotrienes LTB4, LTD4, and delta-6-trans-LTB4 than did tissues obtained during cesarean section. Leukotriene release was stimulated by oxytocin and was inhibited by both BW755c and cycloheximide. These results suggest an activation of the arachidonate lipoxygenase pathway in these tissues during labor. Oxytocin could play a regulatory role in this process.


The OneTogether collaborative approach to reduce the risk of surgical site infection: identifying the challenges to assuring best practice.
Surgical site infections (SSI) account for 16% of healthcare associated infections, and are associated with considerable morbidity, mortality and increased costs of care. Ensuring evidence-based practice to prevent SSI is incorporated across the patient's surgical journey is complex. OneTogether is a quality improvement collaborative of infection prevention and operating department specialists, formed to support the spread and adoption of best practice to prevent SSI. This paper describes the findings of an expert workshop on infection prevention in operating departments. A total of 84 delegates from 75 hospitals attended the workshop, comprising 46 (55%) theatre nurses/operating department practitioners; 16 (19%) infection control practitioners and 22 (26%) other healthcare practitioners. Discussion focused on evidence, policy implementation and barriers to best practice. Responses were synthesised into a narrative review. Delegates reported significant problems in translating evidence-based guidance into everyday practice, lack of local polices and poor compliance. Major barriers were lack of leadership, poorly defined responsibilities, and lack of knowledge/training. This workshop has provided important insights into major challenges in assuring compliance with best practice in relation to the prevention of SSI. The OneTogether partnership aims to support healthcare practitioners to improve the outcomes of patients undergoing surgery by reducing the risk of SSI.


Proteinuria in sickle cell trait and disease: an electrophoretic analysis.
Using ultrafiltration and SDS-PAGE, abnormal urinary protein excretion was found in 25.4% of 189 persons with sickle cell disease and trait, but none of 72 controls. Based upon molecular weight of urinary proteins, underlying renal lesions were classified as glomerular, tubular, or both. Altered protein excretion appeared at an early age, was more abnormal in older subjects, and was related to the severity of sickle cell disease (SS greater than SC = S/beta Thal greater than AS). Since none of the subjects had yet developed clinically significant renal disease, SDS-PAGE may permit early detection of patients who require careful follow-up or aggressive therapy.


Multiple ischemic infarcts in a child with AIDS, varicella zoster infection, and cerebral vasculitis.
A 4 1/2-year-old girl with acquired immunodeficiency syndrome and prolonged varicella zoster virus skin infection developed multiple ischemic strokes and radiologic and histopathologic evidence of central nervous system vasculitis. Typical features of acquired immunodeficiency syndrome encephalitis were not present and there was no evidence of vasculitis outside the nervous system. Central nervous system vasculitis probably resulted from varicella zoster virus infection that persisted because of immunodeficiency. This acquired immunodeficiency syndrome complication has only rarely been described in adults and to our knowledge has not been described in children.


Tissue localization of esterase-5 in Drosophila pseudoobscura.
Disc gel electrophoresis of dissected adults of Drosophila pseudoobscura showed that most of the esterase-5 activity was in the head (36%) and thorax (51%), with little activity in the abdomen (13%). No activity was found in digestive tissues, reproductive tissues, or nervous tissues. Most of the est-5 activity (61%) was found to be associated with hemolymph. However, the eyes contained 39% of the total est-5 activity. These results were supported by spectrophotometric assays of esterase activity in crude extracts of eyes and whole flies without eyes which showed that 27% of the total est-5 activity was in the eyes.


Fermentation performance assessment of a genomically integrated xylose-utilizing recombinant of Zymomonas mobilis 39676.
In pH-controlled batch fermentations with pure sugar synthetic hardwood hemicellulose (1% [w/v] glucose and 4% xylose) and corn stover hydrolysate (8% glucose and 3.5% xylose) lacking acetic acid, the xylose-utilizing, tetracycline (Tc)-sensitive, genomically integrated variant of Zymomonas mobilis ATCC 39676 (designated strain C25) exhibited growth and fermentation performance that was inferior to National Renewable Energy Laboratory's first-generation, Tc-resistant, plasmid-bearing Zymomonas recombinants. With C25, xylose fermentation following glucose exhaustion was markedly slower, and the ethanol yield (based on sugars consumed) was lower, owing primarily to an increase in lactic acid formation. There was an apparent increased sensitivity to acetic acid inhibition with C25 compared with recombinants 39676:pZB4L, CP4:pZB5, and ZM4:pZB5. However, strain C25 performed well in continuous fermentation with nutrient-rich synthetic corn stover medium over the dilution range 0.03-0.06/h, with a maximum process ethanol yield at D = 0.03/h of 0.46 g/g and a maximum ethanol productivity of 3 g/(L x h). With 0.35% (w/v) acetic acid in the medium, the process yield at D = 0.04/h dropped to 0.32 g/g, and the maximum productivity decreased by 50% to 1.5 g/(L x h). Under the same operating conditions, rec Zm ZM4:pZB5 performed better; however, the medium contained 20 mg/L of Tc to constantly maintain selective pressure. The absence of any need for antibiotics and antibiotic resistance genes makes the chromosomal integrant C25 more compatible with current regulatory specifications for biocatalysts in large-scale commercial operations.


6-Hydroxydopamine potentiates acute herpes simplex virus infection of the superior cervical ganglion in mice.
Treatment of mice with 6-hydroxydopamine increased herpes simplex virus replication in the superior cervical ganglion while it decreased the subsequent prevalence of latent infection. Preganglionic neurectomy failed to block this effect. These observations suggest that intrinsic neural events modify the outcome of viral infections of the nervous system.


Associations with multiple pituitary hormone deficiency in patients with an ectopic posterior pituitary gland.
The presence of an ectopic posterior pituitary gland (EPP) on magnetic resonance imaging (MRI) is associated with hypopituitarism with one or more hormone deficiencies. We aimed to identify risk factors for having multiple pituitary hormone deficiency (MPHD) compared to isolated growth hormone deficiency (IGHD) in patients with an EPP. In 67 patients (45 male) with an EPP on MRI, the site (hypothalamic vs. stalk) and surface area (SA) [ x (maximum diameter/2) x (maximum height/2), mm(2)] of the EPP were recorded and compared in patients with IGHD and MPHD in relation to clinical characteristics. In MPHD (n = 32) compared to IGHD (n = 35) patients: age of presentation was younger (1.4 [0.1-10.7]vs. 4.0 [0.1-11.3] years, P = 0.005), major incidents during pregnancy were increased (47%vs. 20%, P = 0.02) as were admissions to a neonatal intensive care unit (NICU) (60%vs. 26%, P = 0.04), whilst EPP SA was lower (12.3 [2.4-34.6]vs. 25.7 [6.9-48.2] mm(2), P < 0.001). In patients with a hypothalamic (n = 56) compared to a stalk sited EPP (n = 11): prevalence of MPHD was greater (55%vs. 9%,P = 0.05) and EPP surface area was smaller (17.3 [2.4-48.2]vs. 25.3 [11.8-38.5] mm(2), P < 0.001). In regression analysis, after adjusting for age, presence of MPHD was associated with: major incidents during pregnancy (RR 6.8 [95%CI 1.2-37.7]), hypothalamic EPP site (RR 10.9 [1.0-123.9]) and small EPP SA (RR 2.5 [1.0-5.0] for tertiles of SA). In patients with an EPP, adverse antenatal events, size (small) and position (hypothalamic) of the posterior pituitary gland on MRI were associated with MPHD. These findings suggest that adverse factors during pregnancy may be important for the development of an EPP.


What is the consequence of an abnormal lipid profile in patients with type 2 diabetes or the metabolic syndrome?
Patients with type 2 diabetes have an atherogenic lipid profile, which greatly increases their risk of coronary heart disease (CHD) compared with people without diabetes. The largest disparity in lipid levels among people with and without diabetes occurs for high-density lipoprotein cholesterol (HDL-C) and triglycerides: triglycerides tend to be markedly higher and HDL-C moderately lower in patients with diabetes, in contrast to the negligible difference observed in low-density lipoprotein cholesterol (LDL-C) and total cholesterol. However, patients with type 2 diabetes are more likely to have the atherogenic form of LDL-C than people without diabetes, as well as low HDL-C, which restricts reverse cholesterol transport and may also be associated with increased lipid oxidation. Among patients who have suffered a myocardial infarction, increased LDL-C is apparent in early adulthood, whereas a detectable difference in HDL-C levels becomes increasingly apparent with age and most pronounced after age 60 years, compared with healthy controls. Evidence indicates that the increased risk of macrovascular complications of type 2 diabetes begins long before the onset of clinical hyperglycaemia. Despite successful reduction of LDL-C with statin therapy, patients continue to be at increased risk for CHD if their HDL-C levels remain suboptimal, in part due to persistence of enhanced lipid exchange. Observational data suggest that increasing HDL-C should be much more potent therapeutically than a similar proportionate decrease in LDL-C.


Cam Osteochondroplasty for Femoroacetabular Impingement Increases Microinstability in Deep Flexion: A Cadaveric Study.
The purpose of this in vitro cadaveric study was to examine the contributions of each surgical stage during cam femoroacetabular impingement (FAI) surgery (i.e., intact-cam hip, T-capsulotomy, cam resection, and capsular repair) toward hip range of motion, translation, and microinstability. Twelve cadaveric cam hips were denuded to the capsule and mounted onto a robotic tester. The hips were positioned in several flexion positions-full extension, neutral (0°), 30° of flexion, and 90° of flexion-and performed internal-external rotations to 5 Nm of torque in each position. The hips underwent a series of surgical stages (T-capsulotomy, cam resection, and capsular repair) and were retested after each stage. Changes in range of motion, translation, and microinstability (overall translation normalized by femoral head radius) were measured after each stage. Regarding range of motion, cam resection increased internal rotation at 90° of flexion (change in internal rotation = +6°, P = .001) but did not affect external rotation. Capsular repair restrained external rotation compared with the cam resection stage (change in external rotation = -8° to -4°, P ≤ .04). In terms of translation, the hip translated after cam resection at 90° of flexion in the medial-lateral plane (change in translation = +1.9 mm, P = .04) relative to the intact and capsulotomy stages. Regarding microinstability, capsulotomy increased microinstability in 30° of flexion (change in microinstability [ΔM] = +0.05, P = .003), but microinstability did not further increase after cam resection. At 90° of flexion, microinstability did not increase after capsulotomy (ΔM = +0.03, P = .2) but substantially increased after cam resection (ΔM = +0.08, P = .03), accounting for a 31% change with respect to the intact stage. Cam resection increased microinstability by 31% during deep hip flexion relative to the intact hip. This finding suggests that iatrogenic microinstability may be due to separation of the labral seal and resected contour of the femoral head. Our in vitro study showed that, at time zero and prior to postoperative recovery, excessive motion after cam resection could disrupt the labral seal. Complete cam resection should be performed cautiously to avoid disruption of the labral seal and postoperative microinstability.


Body mass index and cervical cancer screening among women aged 15-69 years in Eswatini: evidence from a population-based survey.
Cervical cancer stands as one of the most prevalent cancer types among women, despite its preventable nature through early screening and vaccination strategies. The link between being overweight or obese and various adverse health outcomes, including an elevated cancer risk, is well established. Within this study, our central objective was to explore the correlation between body mass index (BMI) and cervical cancer screening (CCS) rates. Moreover, we sought to investigate whether socioeconomic status potentially modulates this relationship. Our analysis encompassed 1791 respondents who participated in the World Health Organization's STEPwise approach to noncommunicable disease risk factor surveillance carried out in Eswatini in 2014. We assessed the connection between BMI, along with other determinants, and CCS through both unadjusted and adjusted logistic regression models. The uptake of CCS was 14.4% and the prevalence of overweight and obesity was estimated at 28.1 and 34.9% respectively. After accounting for other pertinent variables, the likelihood of obtaining CCS was amplified for individuals classified as obese (adjusted odds ratio [aOR] = 1.99, 95% confidence interval [CI] = 1.26-3.12) or overweight (aOR = 1.98, 95% CI = 1.05-3.74). Furthermore, factors such as being separated or divorced (aOR = 2.03, 95% CI = 1.11-3.72) and engaging in regular physical exercise (aOR = 3.02, 95% CI = 1.21-6.02) were associated with increased odds of undergoing CCS. This study underscores the noteworthy role played by both overweight and obesity, in conjunction with various socioeconomic factors, in shaping CCS patterns among the surveyed women. For Eswatini, targeted interventions aimed at enhancing CCS participation should take into account the multifaceted factors highlighted within this investigation.


Synthesis, biological evaluation, and molecular docking studies of cinnamic acyl 1,3,4-thiadiazole amide derivatives as novel antitubulin agents.
A series of cinnamic acyl 1,3,4-thiadiazole amide derivatives (6a-10e) have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferation and tubulin polymerization inhibitors. Among all the compounds, 10e showed the most potent activity in vitro, which inhibited the growth of MCF-7 and A549 cell lines with IC(50) values of 0.28 and 0.52μg/mL, respectively. Compound 10e also exhibited significant tubulin polymerization inhibitory activity (IC(50)=1.16μg/mL). Docking simulation was performed to insert compound 10e into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. Based on the preliminary results, compound 10e with potent inhibitory activity in tumor growth may be a potential anticancer agent.


Iron-deficiency anemia as the sole manifestation of celiac disease.
We report on a 40-year-old woman with a 2-year history of iron-deficiency anemia of unknown origin. Repeated endoscopic investigations in the past had revealed no abnormality of the gastrointestinal system on macroscopic examination. Oral iron supplementation was shown to have no effect on serum iron levels and had no influence on the anemia. Upper gastrointestinal endoscopy performed at our hospital confirmed normal macroscopic findings. However, jejunal biopsies revealed subtotal villous atrophy of the mucosa of the small intestine. A strict gluten-free diet led to an increase in serum iron, resolution of the anemia, and restitution of normal mucosal architecture. Thus iron-deficiency anemia may be the lone manifestation of celiac disease.


Crystallization and a preliminary X-ray diffraction study of isozyme 3-3 of glutathione S-transferase from rat liver.
Crystals of the homodimeric isozyme 3-3 of glutathione S-transferase from rat liver have been obtained with the hanging drop method of vapor diffusion from ammonium sulfate solutions. The successful crystallization of the enzyme required the presence of both the enzyme inhibitor (9R, 10R)-9, 10-dihydro-9-(S-glutathionyl)-10-hydroxyphenanthrene and the detergent beta-octylglucopyranoside. The crystals belong to the monoclinic space group C2, with cell dimensions of a = 88.24(8) A, b = 69.44(4) A, c = 81.28(5) A, beta = 106.01(6) degrees, and contain four dimeric enzyme molecules per unit cell. The crystals diffract to at least 2.2 A and are suitable for X-ray crystallographic structure determination at high resolution.


The 11q-- syndrome: another case report.
The clinical findings and developmental progress of a female infant with karyotype 46,XX,del(11)(q23) are described. Comparison is made with five other reported cases, and the suggestion of a new syndrome del 11q--is supported.


5-(4-Fluoro-phen-yl)-1-[4-(4-methyl-phen-yl)thia-zol-2-yl]-3-[4-(prop-2-yn-yloxy)phen-yl]-4,5-di-hydro-1H-pyrazole.
In the title compound, C28H22FN3OS, four rings are almost coplanar, with the fluorophenyl ring substantially twisted. In the extended structure, aromatic π-π stacking inter-actions between the pyrazole ring and the tolyl ring link the mol-ecules into centrosymmetric dimers.


Pseudosepsis after myocardial infarction. Unusual presentation of anterior wall rupture and left ventricular pseudoaneurysm.
Left ventricular pseudoaneurysm complicating myocardial infarction is extremely rare. A case of left ventricular anterolateral pseudoaneurysm with its initial presentation mimicking septic shock is reported. The need for urgent resection is stressed due to the high incidence of spontaneous rupture and death regardless of the age or the size of the pseudoaneurysm.


Molecular dynamics study of the isothermal crystallization mechanism of polyethylene chain: the combined effects of chain length and temperature.
A molecular level understanding of the polyethylene (PE) crystallization process was elucidated by molecular dynamics simulation of three states, with varying chain length and temperature. The process can be classified into the following three states: (1) nucleation controlled state, (2) competitive state of crystal growth process and new nuclei formation, and (3) crystal growth controlled state, which could be quantified by the evolution of nuclei number. With increasing chain length, two phenomena occur: the single crystallization mechanism changes from state (1) to (3), and the crystal size increases while the b/a axial ratio in the lateral surface decreases. These changes can be explained from a thermodynamic point of view, in that the van der Waals (vdW) interaction per CH2 unit is strengthened and more nucleation sites are generated for longer chain. Size effect (meaning different surface fractions when the chain collapses into a globule) was an important factor determining vdW energy per unit and the crystallization states of a single PE chain. On the other hand, the crystallization states were independent of chain length for short chains systems with the same size effect. In both conditions, a long chain generates multi-crystal domains, and a short chain prefers a single crystal domain. Our results not only provide molecular level evidence for crystallization states but also clarify the influence of chain length on the crystallization process.


T-DNA presence and opine production in tumors of Picea abies (L.) Karst induced by Agrobacterium tumefaciens A281.
The hypervirulent Agrobacterium tumefaciens strain A281 formed frequent tumors (31%) on Picea abies (Norway spruce), an economically important tree species in Swedish forests. Three-month-old seedlings were inoculated and tumors were established that grew hormone-independently in culture. Tumors contained agropine and mannopine/mannopinic acid as determined by acid pH paper electrophoresis. In addition, DNA hybridization studies showed that the DNA from these tumor lines contained sequences homologous to Ti plasmid T-DNA, whereas wild-type spruce seedling DNA did not. These results suggest that Agrobacterium vectors can be used for gene transfer into this important forest species.


Carotid automated ultrasound double line extraction system (CADLES) via Edge-Flow.
This paper presents a completely user-independent algorithm, that automatically extracts the far (distal) double line (lumen-intima and media-adventitia) in the carotid artery using an Edge Flow technique (a class of AtheroEdge™ systems) based on directional probability maps using the attributes of intensity and texture. The extracted double line translates into a measure of the intima-media thickness (IMT), a validated marker for the progression of atherosclerosis. The Carotid Automated Double Line Extraction System based on Edge-Flow (CADLES-EF) is characterized and validated by comparing the output of the algorithm with two other completely automatic techniques (CALEXia and CULEXsa) published by the same authors. Validation was performed on a multi-institutional database of 300 longitudinal B-mode carotid images with normal and pathologic arteries. CADLES-EF showed an intima-media thickness (IMT) bias of 0.043 ± 0.097 mm in comparison to CALEXia and CULEXsa that showed 0.134 ± 0.0.88 mm and 0.74 ± 0.092 mm, respectively. The system's Figure of Merit (FoM) showed an improvement when compared to previous automated methods: CALEXia and CULEXsa, leading to values of 84.7%, 91.5%, while our new approach, CADLES-EF performed the best with 94.8%.


Deleterious effect in endothelin receptor-mediated coronary artery smooth muscle contractility in high-salt diet rats.
High-salt diet has been suggested to increase the risk of heart disease. However, the mechanisms underlying coronary artery tension dysfunction caused by high-salt diet are unclear. Previous studies have shown that coronary artery spasm is often induced by endothelin-1 (ET-1) and thromboxane, leading to myocardial ischemia, while the store-operated Ca2+ entry (SOCE) function of coronary smooth muscle is very important in this process. Tension measurements of endothelium-denuded coronary artery ring segments showed that vasocontraction induced by U46619, ET-1, orSTIM1/Orai1-mediated SOCE was significantly lower in 4% high-salt diet rats than in control rats fed a regular diet. The results of western blotting and immunohistochemistry assays showed lower expression levels of endothelial receptors ETA and ETB, STIM1 and Orai1 in coronary artery of high-salt intake rats compared with control rats. Fibrosis was observed by using Masson's trichrome staining and picrosirius red staining. The plasma ET-1 concentration in high-salt diet rats was significantly higher than that of controls. The interventricular septum and posterior wall of high-salt diet rats were significantly thickened. Our findings indicated that coronary artery tension was significantly decreased in 4% high-salt diet rats and that this decrease may be due to the change of endothelin receptor and its downstream pathway SOCE related protein expression in coronary artery. Coronary fibrosis was observed in rats fed with high-salt diet. This study provides potential mechanistic insights into high-salt intake-induced heart disease.


Prevalence of blindness and low vision: a study in the rural Heilongjiang Province of China.
The prevalence of blind individuals in the north of China is unknown. The study aimed to investigate the prevalence and causes of blindness and low vision in rural areas in Heilongjiang province of China in 2008-2009. Cross-sectional study. A cluster random sampling method was used to recruit participants of all ages in rural areas of Heilongjiang. Trained professionals performed interviews and clinical examinations to measure visual acuity. The relationships between blindness or low vision and age, gender and education level were analysed. The main outcome measure was prevalence rates of bilateral blindness and bilateral low vision. Of the 11 787 subjects, 10 384 (88.1%) were surveyed. The overall age-adjusted prevalence rates were 0.7% (95% confidence interval: 0.5-0.8%) for bilateral blindness and 1.7% (95% confidence interval: 1.4-1.9%) for bilateral low vision. The prevalence rates of blindness and low vision were higher in the elderly and uneducated population (P < 0.05). The main causes for blindness and low vision were cataracts (44.1 and 46.0%, respectively) and refractive errors (17.7 and 42.5%, respectively). Blindness and low vision are highly prevalent among people with cataracts and refractive errors. Eye care planning must focus on treating the avoidable and curable forms of blindness.


Risk of colectomy in patients with ulcerative colitis under thiopurine treatment.
Little is known about the risk factors of colectomy in patients with ulcerative colitis (UC) under thiopurine treatment. The aim of the study was to determine the prevalence and the predictive risk factors of colectomy in an extensive cohort of patients with UC treated with thiopurines in Spain. Among 5753 UC patients, we identified those diagnosed between 1980 and 2009 and treated with azathioprine or mercaptopurine (AZA/MP). We analyzed the age at diagnosis, familial history of IBD, extraintestinal manifestations (EIMs), disease extent, smoking status and treatment requirements (AZA/MP, cyclosporine (CsA) or anti-TNFα). Colectomies for dysplasia or cancer were excluded. Survival analysis and Cox proportional hazard regression were performed. Results were reported as hazard ratios (HR) with 95% CI. Among the 1334 cases included, 119 patients (8.9%) required colectomy after a median time of 26 months (IQR 12-42) after AZA/MP initiation. Independent predictors of colectomy were: Extensive UC (HR 1.7, 95% CI: 1.1-2.6), EIMs (HR 1.5, 95% CI: 1.0-2.4), need for antiTNFα (HR 2.3, 95% CI: 1.5-3.4) and need for CsA (HR 2.4, 95% CI: 1.6-3.7). Patients requiring early introduction of AZA/MP had an increased risk of colectomy with a HR of 4.9 (95% CI: 3.2-7.8) when AZA/MP started in the first 33 months after UC diagnosis. Nearly one-tenth of patients with UC under thiopurines require colectomy. Extensive UC, EIMs, need for CsA or anti-TNFα ever and an early need for AZA/MP treatment were associated with a higher risk of colectomy. These risk factors of colectomy could help to stratify risk in further controlled studies in UC.


A Comparison of Generic and Condition-Specific Preference-Based Measures Using Data From Nivolumab Trials: EQ-5D-3L, Mapping to the EQ-5D-5L, and European Organisation for Research and Treatment of Cancer Quality of Life Utility Measure-Core 10 Dimensions.
There is growing interest in condition-specific preference measures, including the European Organisation for Research and Treatment of Cancer Quality of Life Utility Measure-Core 10 Dimensions (QLU-C10D). This research assessed the implications of using utility indices on the basis of the EQ-5D-3L, a mapping of EQ-5D-3L to the EQ-5D-5L, and the QLU-C10D, and compared their psychometric properties. Data were taken from 8 phase 3 randomized controlled trials of nivolumab with or without ipilimumab for the treatment of solid tumors. Utilities for progression-related states were calculated using the UK and English value sets and incremental quality-adjusted life-years (QALYs) derived from established UK cost-effectiveness models. The psychometric properties of the utility indices were assessed using pooled trial data. Compared with the EQ-5D-3L index, the mapped EQ-5D-5L index yielded an average of 6% more and the QLU-C10D index an average of 2% fewer incremental QALYs for nivolumab versus comparators. All indices could differentiate between groups defined by performance status, cancer stage, or self-reported health status at baseline and detect meaningful changes in performance status, tumor response, health status, and quality of life over approximately 12 weeks of treatment. The lower QALY yield of the QLU-C10D was balanced by evidence of greater validity and responsiveness. Benefits gained from using the QLU-C10D may be apparent when treatments affect targeted symptoms and functional aspects, including sleep, bowel function, appetite, nausea, and fatigue. The observed differences in QALYs may not be sufficiently large to affect health technology assessment decisions.


Unicystic ameloblastoma. A review of 193 cases from the literature.
Based on a world-wide literature survey of 193 published cases of unicystic ameloblastomas (UA), data have been produced allowing the presentation of a revised concept of this much debated lesion. UA is a variant of the solid or multicystic ameloblastoma. Radiographically, the unilocular pattern is more common that the multilocular, especially in cases associated with tooth impaction. However, it is stressed that although the lesion is pathomorphologically unicystic, it will far from always produce a unilocular radiolucency. The mean age at the time of diagnosis of UA is closely related to an association with an impacted tooth. Almost 20 years separate the mean age of the 'dentigerous' variant from the 'non-dentigerous' (16.5 years versus 35.2 years) The male:female ratio for the 'dentigerous' type is 1.5:1, but for the 'non-dentigerous' type it is reversed (1:1.8). Location favours greatly the mandible (mandible to maxilla = 3 to 13:1). Between 50 and 80% of cases are associated with tooth impaction, the mandibular third molar being most often involved. The 'dentigerous' type occurs on average 8 years earlier than the 'non-dentigerious' variant. The mean age for unilocular, impaction-associated UAs is 22 years, whereas the mean age for the multilocular lesion unrelated to an impacted tooth is 33 years. Histologically, the minimum criterion for diagnosing a lesion as UA is the demonstration of a single cystic sac lined by odontogenic (ameloblastomatous) epithelium often seen only in focal areas. This simple type of UA (according to the authors' modification of the classification by Ackermann et al. (Journal of Oral Pathology 1988; 17:541-546)), is one of four UA subtypes, the others being (1) simple with intralumenal proliferations; (2) simple with both intralumenal and intramural proliferations; and (3) simple with intramural proliferations only. All four subtypes occur in both the 'dentigerous' and 'non-dentigerous' variants. The simple subtype with and without intralumenal proliferations may be treated conservatively (enucleation), whereas subtypes showing intramural growths must be treated radically, i.e. as a solid or multicystic ameloblastoma. Finally, the authors disclose areas and issues pertaining to UA that still need to be addressed.


Studies of peptide antibiotics. XLIII. Syntheses of gramicidin S analogs containing D-serine or dehydroalanine in place of D-phenylalanine and asymmetric hydrogenation of the dehydroalanine residue.
Gramicidin S (GS) analogs, [D-Ser4,4']-GS and its precursor [O-benzyl-D-Ser4,4']-GS, were synthesized by the conventional method in order to evaluate the role of the hydroxymethyl side chains in D-Ser at 4,4' positions on the biological activity. Another analog [L-Orn(delta-Boc)2,2',delta Ala4,D-Ser4']-GS was prepared from [D-Ser4,4']-GS by t-butyloxycarbonylation and successive dehydration using dicyclohexylcarbodiimide-CuCl as dehydrating reagent. The delta Ala residue was asymmetrically hydrogenated to D-Ala in the presence of Pd-black. On the microbial assays, [O-benzyl-D-Ser4,4']-GS showed high antimicrobial activity as natural GS, but [D-Ser4,4']-GS showed low activity; the structure-activity relationships of the analogs were discussed.


Computational Modeling to Determine the Effect of Phenotypic Heterogeneity in Tumors on the Collective Tumor-Immune Interactions.
Tumor immunotherapy aims to maintain or enhance the killing capability of CD8+ T cells to clear tumor cells. The tumor-immune interactions affect the function of CD8+ T cells. However, the effect of phenotype heterogeneity of a tumor mass on the collective tumor-immune interactions is insufficiently investigated. We developed the cellular-level computational model based on the principle of cellular Potts model to solve the case mentioned above. We considered how asymmetric division and glucose distribution jointly regulated the transient changes in the proportion of proliferating/quiescent tumor cells in a solid tumor mass. The evolution of a tumor mass in contact with T cells was explored and validated by comparing it with previous studies. Our modeling exhibited that proliferating/quiescent tumor cells, exhibiting distinct anti-apoptotic and suppressive behaviors, redistributed within the domain accompanied by the evolution of a tumor mass. Collectively, a tumor mass prone to a quiescent state weakened the collective suppressive functions of a tumor mass on cytotoxic T cells and triggered a decline of apoptosis of tumor cells. Although quiescent tumor cells did not sufficiently do their inhibitory functions, the possibility of long-term survival was improved due to their interior location within a mass. Overall, the proposed model provides a useful framework to investigate collective-targeted strategies for improving the efficiency of immunotherapy.


Repair response of human fibroblasts to bleomycin damage.
The ability of human fibroblasts to repair the specific types of DNA damage caused by bleomycin (BLM) was examined in whole-cell experiments. The method utilized for analysis was alkaline sucrose-gradient centrifugation of DNA. The results of these studies show that a repair pathway exists for the damage produced in DNA by bleomycin. DNA from BLM-treated cells shows a decrease in molecular weight, caused by chemical or enzymatic incision at sites of drug action. If the drug is removed, the DNA rapidly returns to high molecular weight, demonstrating reformation of damaged DNA. This repair response to BLM-damage was also confirmed in fibroblasts isolated from patients with putative DNA-repair defects. We observed that the response (to BLM) of cells from patients with Fanconi anemia was altered in that the fall in molecular weight of DNA from treated cells was not as great as that observed in other cell strains after drug treatment.


A rare case of impending paradoxical embolism with a complex patent foramen ovale.
A 68-year-old woman, who presented with pulmonary embolism, was diagnosed as having an impending paradoxical thromboembolism by transthoracic and transesophageal echocardiography, which revealed an entrapped thrombus in the atrial septum. The patient underwent surgery for thromboembolectomy. A patent foramen ovale (PFO) appeared as a tunnel with three openings into the left atrium; one opening located close to the antero-superior left atrial wall and two small atrial septal defects of a septum primum. A thrombus was trapped at two small atrial septal defects. This was a rare case of impending paradoxical embolism with complex morphology of PFO.


Relation of bronchioloalveolar carcinoma to tobacco.
To determine whether bronchioalveolar carcinoma is related to tobacco use. Case-control study. 11 teaching hospitals of Chicago, Long Island, New York, and Philadelphia, 1977-89. 87 patients with histologically diagnosed bronchioloalveolar carcinoma (cases) and 286 non-cancer and 297 cancer patients matched to cases on age, sex, race, hospital, and date of admission. 10% of male cases and 25% of female cases had never smoked. Relative risks of bronchioloalveolar carcinoma (as estimated by the relative odds) were greater for subjects who started smoking at a younger age, smoked for a longer time, or smoked more cigarettes per day. Relative risks decreased proportionally to the duration of smoking cessation. Smoking plays an important part in the aetiology of bronchioloalveolar carcinoma but is not the only potential cause because of the large proportion of never smokers among patients with this disease.


[Surgical management of a recurrent iris stromal cyst].
Cysts of the iris stroma may be congenital or acquired. They are rare tumors of the anterior segment. We describe the case of a 51-year-old patient presenting with a recurrent iris stromal cyst. The patient presented emergently for sudden recurrence of an iris stromal cyst with decreased visual acuity. He had already undergone needle aspiration and argon laser photocoagulation of the cyst 1 year previously. A Ultrasound BioMicroscopy (UBM) examination was performed to rule out any malignant tumor of the iris or ciliary body. Surgical treatment consisted of complete removal of the external layer of the cyst with Implantable Contact Lens (ICL) forceps after marsurpialization with scissors. The postoperative course was uneventful. Cysts of the iris stroma are rare benign tumors that pose problems due to their extension into the anterior chamber and recurrence.


[Adolescent bicipitoradial bursitis: a rare disease that can simulate a malignant tumor].
Bicipitoradial bursitis is a rare condition: we found 36 cases reported in the literature, none in children. The main manifestation is a painful tumefaction. We report a case observed in an adolescent whose magnetic resonance imaging findings were compatible with a malignant tumor. Surgical biopsy enabled the correct diagnosis of inflammatory synovium without signs of malignancy compatible with bicipitoradial bursitis. Complete cure was achieved without resection.


Designing, fabrication and evaluation of a rapid, point-of-care and noninvasive system for the detection of lead (Pb2+).
Non-invasive collection of biological sample such as sweat, urine, saliva, hairs and, stool and onsite detection of anlaytes in those samples is an interesting and viable approach for rapid screening of various toxicants in body. Environmental exposure/presence of lead (82Pb) and its rapid detection provide one such opportunity. A chemical spot based colorimetric method and a transdermal patch device based on this spot test, is developed for rapid and qualitative assessment of inorganic lead (Pb2+) in non-coloured biological or environmental liquid samples. The transdermal patch system contains two important parts, a chemical spot prepared on a thin glass sheet and, an absorbent paper (11 µm pore size). A one step colour development reaction is able to identify the presence or absence of Pb2+. In-vitro evaluation for sensitivity and cut-off value determination, within run and between run precision testing, specificity testing were done. In-vivo evaluation of the developed patch system was performed in occupationally lead-exposed subjects and in control volunteers. In-vivo field testing results were further validated with gold standard test for lead detection. Blood lead levels and patch lead levels were found to be positively correlated (r = 0.57, P < 0.0001). In addition, the sensitivity and specificity of device in identification of Pb2+ was found to be 75.93% (95% CI = 62.36%-86.51%) and 95.24% (95% CI = 76.18%-99.88%). The developed system appears as a reliable, non-invasive rapid test with minimum step involve for identification of Pb2+ in a given system.


The Validation of a Case-Based, Cumulative Assessment and Progressions Examination.
To assess content and criterion validity, as well as reliability of an internally developed, case-based, cumulative, high-stakes third-year Annual Student Assessment and Progression Examination (P3 ASAP Exam). Content validity was assessed through the writing-reviewing process. Criterion validity was assessed by comparing student scores on the P3 ASAP Exam with the nationally validated Pharmacy Curriculum Outcomes Assessment (PCOA). Reliability was assessed with psychometric analysis comparing student performance over four years. The P3 ASAP Exam showed content validity through representation of didactic courses and professional outcomes. Similar scores on the P3 ASAP Exam and PCOA with Pearson correlation coefficient established criterion validity. Consistent student performance using Kuder-Richardson coefficient (KR-20) since 2012 reflected reliability of the examination. Pharmacy schools can implement internally developed, high-stakes, cumulative progression examinations that are valid and reliable using a robust writing-reviewing process and psychometric analyses.


Epithelioid hemangioma (ALHE) on the tongue of an infant treated with oral corticosteroids: A case report and review of the literature.
Epithelioid hemangioma or angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare benign vascular lesion presenting as multiple nodules on the head and neck. Surgery had been considered to be the best treatment modality for ALHE. We report the case of a 6-month-old boy with ALHE on his tongue that was treated successfully with oral prednisolone.


Development of programmable gemcitabine-GnRH pro-drugs bearing linker controllable "click" oxime bond tethers and preclinical evaluation against prostate cancer.
Peptide-drug conjugates (PDCs) are gaining considerable attention as anti-neoplastic agents. However, their development is often laborious and time-consuming. Herein, we have developed and preclinically evaluated three PDCs with gemcitabine as the anticancer cytotoxic unit and D-Lys6-GnRH (gonadotropin-releasing hormone; GnRH) as the cancer-targeting unit. These units were tethered via acid-labile programmable linkers to guide a differential drug release rate from the PDC through a combination of ester or amide and "click" type oxime ligations. The pro-drugs were designed to enable the selective targeting of malignant tumor cells with linker guided differential drug release rates. We exploited the oxime bond responsiveness against the acidic pH of the tumor microenvironment and the GnRH endocytosis via the GnRH-R GPCR which is overexpressed on cancer cells. The challenging metabolic properties of gemcitabine were addressed during design of the PDCs. We developed a rapid (1 hour) and cost-effective "click" oxime bond ligation platform to assemble in one-pot the 3 desired PDCs that does not require purification, surpassing traditional time-ineffective and low yield methods. The internalization of the tumor-homing peptide unit in cancer cells, overexpressing the GnRH-R, was first validated through confocal laser microscopy and flow cytometry analysis. Subsequently, the three PDCs were evaluated for their in vitro antiproliferative effect in prostate cancer cells. Their stability and the release of gemcitabine over time were monitored in vitro in cell culture and in human plasma using LC-MS/MS. We then assessed the ability of the developed PDCs to internalize in prostate cancer cells and to release gemcitabine. The most potent analog, designated GOXG1, was used for pharmacokinetic studies in mice. The metabolism of GOXG1 was examined in liver microsomes, as well as in buffers mimicking the pH of intracellular organelles, resulting in the identification of two metabolites. The major metabolite at low pH emanated from the cleavage of the pH-labile oxime bond, validating our design approach. NMR spectroscopy and in vitro radioligand binding assays were exploited for GOXG1 to validate that upon conjugating the drug to the peptide, the peptide microenvironment responsible for its GnRH-R binding is not perturbed and to confirm its high binding potency to the GnRH-R. Finally, the binding of GOXG1 to the GnRH-R and the associated elicitation of testosterone release in mice were also determined. The facile platform established herein for the rapid assembly of PDCs with linker controllable characteristics from aldehyde and aminooxy units through rapid "click" oxime ligation, that does not require purification steps, could pave the way for a new generation of potent cancer therapeutics, diagnostics and theranostics.


Spontaneous resolution of asymptomatic alumina matrix composite ceramic liner dissociation: a case report.
Total hip arthroplasty(THA)is widely used to treat end-stage hip disorders. Ceramic-on-ceramic total hip prostheses are widely used because of their durability. Alumina matrix composite (AMC), known as the fourth-generation ceramics, reduces implant fracture and wear rate compared to their predecessors. However, ceramic acetabular liner dissociation is a complication that necessitates revision of the AMC prostheses. To date, only few cases of AMC liner dissociation have been reported and all of which have been treated with revision surgery. Therefore, the prognosis of non-operated AMC liner dissociation remains unknown so far. A 57-year-old man with avascular necrosis of the femoral head was treated with THA, wherein a Pinnacle® (DePuy, J&J, Warsaw, IN) acetabular cup and AMC liner were implanted. Intraoperative examination confirmed proper seating of the liner, whereas the initial postoperative radiograph revealed liner dissociation. The patient refused surgical revision due to the absence of symptoms and was discharged and followed-up. The patient made an uneventful recovery, and radiographic follow-up at 6-month post-operation showed that the liner was re-seated to its right position. No clinical or radiographic anomaly was found at the 15-month of postoperative follow-up. Here, we report an unprecedented case of AMC ceramic liner dissociation with spontaneous resolution. This case shows that ceramic liner dissociation could be asymptomatic, and careful postoperative examination of the patient is important. Spontaneous resolution is possible, but the underlying mechanism and the eligible patient to benefit from it must be investigated. Before clarifying these questions, revision surgery should be the first-line treatment.


Copy Number Variation Analysis by Array Analysis of Single Cells Following Whole Genome Amplification.
Whole genome amplification is required to ensure the availability of sufficient material for copy number variation analysis of a genome deriving from an individual cell. Here, we describe the protocols we use for copy number variation analysis of non-fixed single cells by array-based approaches following single-cell isolation and whole genome amplification. We are focusing on two alternative protocols, an isothermal and a PCR-based whole genome amplification method, followed by either comparative genome hybridization (aCGH) or SNP array analysis, respectively.


Fatal crashes among older drivers: decomposition of rates into contributing factors.
This study selected US drivers aged 55 years or older who were involved in fatal crashes in 1990 and 1995 and explored factors that influenced their fatal crash involvement rate. The fatal crash involvement rate (risk of being involved in a fatal crash) can be thought of as the product of the crash fatality rate (risk of dying given a crash), the crash incidence density (risk of crash), and the exposure prevalence (amount of driving). Fatal crash involvement rates increased with age. The relative contributions of the crash incidence densities and exposure prevalences were greater than that of the crash fatality rates. The decomposition methodology was shown to be a useful method for investigating the potential benefit of crash prevention interventions aimed at different components of the fatal crash involvement rate.


Comparative genome analysis of the candidate functional starter culture strains Lactobacillus fermentum 222 and Lactobacillus plantarum 80 for controlled cocoa bean fermentation processes.
Lactobacillus fermentum 222 and Lactobacillus plantarum 80, isolates from a spontaneous Ghanaian cocoa bean fermentation process, proved to be interesting functional starter culture strains for cocoa bean fermentations. Lactobacillus fermentum 222 is a thermotolerant strain, able to dominate the fermentation process, thereby converting citrate and producing mannitol. Lactobacillus plantarum 80 is an acid-tolerant and facultative heterofermentative strain that is competitive during cocoa bean fermentation processes. In this study, whole-genome sequencing and comparative genome analysis was used to investigate the mechanisms of these strains to dominate the cocoa bean fermentation process. Through functional annotation and analysis of the high-coverage contigs obtained through 454 pyrosequencing, plantaricin production was predicted for L. plantarum 80. For L. fermentum 222, genes encoding a complete arginine deiminase pathway were attributed. Further, in-depth functional analysis revealed the capacities of these strains associated with carbohydrate and amino acid metabolism, such as the ability to use alternative external electron acceptors, the presence of an extended pyruvate metabolism, and the occurrence of several amino acid conversion pathways. A comparative genome sequence analysis using publicly available genome sequences of strains of the species L. plantarum and L. fermentum revealed unique features of both strains studied. Indeed, L. fermentum 222 possessed genes encoding additional citrate transporters and enzymes involved in amino acid conversions, whereas L. plantarum 80 is the only member of this species that harboured a gene cluster involved in uptake and consumption of fructose and/or sorbose. In-depth genome sequence analysis of the candidate functional starter culture strains L. fermentum 222 and L. plantarum 80 revealed their metabolic capacities, niche adaptations and functionalities that enable them to dominate the cocoa bean fermentation process. Further, these results offered insights into the cocoa bean fermentation ecosystem as a whole and will facilitate the selection of appropriate starter culture strains for controlled cocoa bean fermentation processes.


[Association of HLA-DRB genes with Vogt-Koyanagi-Harada syndrome in a Chinese Han population].
To investigate the molecular genetic background of VKH syndrome in Han Chinese by HLA-DRB genotyping. HLA-DRB genotyping was performed by PCR-SSOP method, then DR4 alleles were analyzed by SSOP and RFLP methods. The frequency of DRB1 * 0405 was significantly higher in VKH patients than that in normal controls (80.4% vs 8.1%, Pc < 10(-7), RR = 46.7), so was the frequency of DRB1 * 15 in DRB1 * 0405 negative individuals (Pc < 0.05, RR = 6.0). On the other hand, the frequencies of DRB1 * 14 and DRB1 * 08 were significantly lower in VKH patients than that in normal controls. Comparing the clinical features between DRB1 * 0405 positive and negative VKH patients, no significant differences were found. (1) DRB1 * 0405 and DRB1 * 15 are closely associated with the susceptibility to VKH syndrome, DRB1 * 0405 may be the major susceptible gene and DRB1 * 15 may be the minor; (2) DRB1 * 14 and DRB1 * 08 are negatively associated with the susceptibility to VKH syndrome, suggesting that they may be the resistant genes; (3) DRB1 * 0405 is not related to the clinical features, incidence of ocular complications as well as visual prognosis.


Exacerbation of diabetic renal failure following intravenous pyelography.
Twenty-two of 29 (76 per cent) diabetic patients with a creatinine level of more than 2 mg/100 ml had exacerbation of renal failure following intravenous pyelography. In nine patients this was irreversible. Particularly at risk seem to be patients with early onset diabetes (less than 40 years), and those patients with severe renal failure (creatine over 5 mg/100 ml). No less that 15 of 16 (93 per cent) such patients had problems after intravenous pyelography; of these, nine (56 per cent) had irreversible deterioration. This report, in context with the increasing number of case reports of similar findin.gs, indicates that intravenous pyelography is dangerous in patients with juvenile onset diabetes who have a creatinine level of more than 5 mg/100 ml.


Secondary necrosis in multicellular animals: an outcome of apoptosis with pathogenic implications.
In metazoans apoptosis is a major physiological process of cell elimination during development and in tissue homeostasis and can be involved in pathological situations. In vitro, apoptosis proceeds through an execution phase during which cell dismantling is initiated, with or without fragmentation into apoptotic bodies, but with maintenance of a near-to-intact cytoplasmic membrane, followed by a transition to a necrotic cell elimination traditionally called "secondary necrosis". Secondary necrosis involves activation of self-hydrolytic enzymes, and swelling of the cell or of the apoptotic bodies, generalized and irreparable damage to the cytoplasmic membrane, and culminates with cell disruption. In vivo, under normal conditions, the elimination of apoptosing cells or apoptotic bodies is by removal through engulfment by scavengers prompted by the exposure of engulfment signals during the execution phase of apoptosis; if this removal fails progression to secondary necrosis ensues as in the in vitro situation. In vivo secondary necrosis occurs when massive apoptosis overwhelms the available scavenging capacity, or when the scavenger mechanism is directly impaired, and may result in leakage of the cell contents with induction of tissue injury and inflammatory and autoimmune responses. Several disorders where secondary necrosis has been implicated as a pathogenic mechanism will be reviewed.


CDK4/6 inhibitors in breast cancer: differences in toxicity profiles and impact on agent choice. A systematic review and meta-analysis.
Introduction: CDK4/6 inhibitor approval for hormone-responsive breast tumors has significantly changed therapeutic algorithms, with three drugs currently approved.Areas covered: Here, we analyze the toxicity profiles of palbociclib, ribociclib, and abemaciclib through a systematic review and meta-analysis. Palbociclib and ribociclib showed high rates of hematological toxicity, primarily neutropenia, and were associated with a low rate of severe infections. Abemaciclib was associated with a high rate of gastrointestinal toxicities, primarily diarrhea, of grade 1-2 in most cases. Ribociclib was associated with a high rate of hepatic, and respiratory toxicity and with QTc prolongation. The toxicity rate of ribociclib was higher in metastatic patients than non-metastatic patients, with approximately 33% more grade 3-4 toxicities and 21% more grade 3-4 neutropenic events. A 5% higher risk of diarrhea was observed in postmenopausal patients. Pre-treated patients did not show a higher toxicity rate for palbociclib/ribociclib than previously untreated patients, while a 26% higher risk of any grade neutropenia and 6% higher risk of grade 3-4 diarrhea were observed with abemaciclib.Expert opinion: Considering the similar efficacies and indications of palbociclib, ribociclib, and abemaciclib, the evaluation of their toxicity profiles may facilitate treatment choice.


Immunoadsorption therapy in patients with multiple sclerosis with steroid-refractory optical neuritis.
In multiple sclerosis relapses refractory to intravenous corticosteroid therapy, plasma exchange is recommended. Immunoadsorption (IA) is regarded as an alternative therapy, but its efficacy and putative mechanism of action still needs to be established. We prospectively treated 11 patients with multiple sclerosis who had optical neuritis and fulfilled the indications for apheresis therapy (Trial registration DE/CA25/00007080-00). In total, five IA treatments were performed using tryptophan-IA. Clinical activity (visual acuity, Expanded Disability Status Scale, Incapacity Status Scale), laboratory values and visual evoked potentials were measured before, during and after IA, with a follow-up of six months. Moreover, proteomic analyses were performed to analyze column-bound proteins as well as corresponding changes in patients' sera. After the third IA, we detected an improvement of vision in eight of eleven patients, whom we termed responders. Amongst these, the mean visual acuity improved from 0.15 ± 0.12 at baseline to 0.47 ± 0.32 after the third IA (P = 0.0252) up to 0.89 ± 0.15 (P < 0.0001) at day 180 ± 10 after IA. Soluble interleukin-2 receptor decreased in responders (P = 0.03), whereas in non-responders it did not. Proteomic analyses of proteins adsorbed to IA columns revealed that several significant immunological proteins as well as central nervous system protein fragments, including myelin basic protein, had been removed by IA. IA was effective in the treatment of corticosteroid-refractory optic neuritis. IA influenced the humoral immune response. Strikingly, however, we found strong evidence that demyelination products and immunological mediators were also cleared from plasma by IA.


Polygenic risk scores point toward potential genetic mechanisms of type 2 myocardial infarction in people with HIV.
People with human immunodeficiency virus (HIV) infection (PWH) are at higher risk of myocardial infarction (MI) than those without HIV. About half of MIs in PWH are type 2 (T2MI), resulting from mismatch between myocardial oxygen supply and demand, in contrast to type 1 MI (T1MI), which is due to primary plaque rupture or coronary thrombosis. Despite worse survival and rising incidence in the general population, evidence-based treatment recommendations for T2MI are lacking. We used polygenic risk scores (PRS) to explore genetic mechanisms of T2MI compared to T1MI in PWH. We derived 115 PRS for MI-related traits in 9541 PWH enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort with adjudicated T1MI and T2MI. We applied multivariate logistic regression analyses to determine the association with T1MI and T2MI. Based on initial findings, we performed gene set enrichment analysis of the top variants composing PRS associated with T2MI. We found that T1MI was strongly associated with PRS for cardiovascular disease, lipid profiles, and metabolic traits. In contrast, PRS for alcohol dependence and cholecystitis, significantly enriched in energy metabolism pathways, were predictive of T2MI risk. The association remained after the adjustment for actual alcohol consumption. We demonstrate distinct genetic traits associated with T1MI and T2MI among PWH further highlighting their etiological differences and supporting the role of energy regulation in T2MI pathogenesis.


Glyceryl trinitrate-induced blood pressure variability decrease during head-up tilt test predicts vasovagal response.
Glyceryl trinitrate (GTN) provoked cardioinhibitory syncope during the head-up tilt test is preceded by a period of disrupted blood pressure variability (BPV). Endogenous nitric oxide (NO) attenuates BPV independently of blood pressure (BP). We hypothesized that exogenous NO donor GTN might decrease BPV during the presyncope period. A decrease in BPV may predict the tilt outcome. We analyzed 29 tilt test recordings of subjects with GTN-induced cardioinhibitory syncope and 30 recordings of negative subjects. A recursive autoregressive model of BPV after GTN was performed; powers of the respiratory (0.15-0.45 Hz) and nonrespiratory frequency (0.01-0.15 Hz) bands were calculated for each of the 20 normalized time periods. The post-GTN relative changes in heart rate, BP, and BPV were calculated. In the syncope group, spectral power of nonrespiratory frequency systolic and diastolic BPV progressively felt for 30% after GTN application and stabilized after 180 s. BP started to fall 240 s after the GTN application. Decrease in nonrespiratory frequency power of diastolic BPV 20 s after GTN administration predicted cardioinhibitory syncope (area under the curve 0.811; 77% sensitivity; 70% specificity; cutoff value > 7%). GTN application during the tilt test attenuates systolic and diastolic nonrespiratory frequency BPV during the presyncope period, independent of BP. A decrease in nonrespiratory frequency diastolic BPV 20 s after GTN application predicts cardioinhibitory syncope with good sensitivity and moderate specificity.


Distinct roles of Rab3B and Rab13 in the polarized transport of apical, basolateral, and tight junctional membrane proteins to the plasma membrane.
Regulated transport of proteins to distinct plasma membrane domains is essential for the establishment and maintenance of cell polarity in all eukaryotic cells. The Rab family small G proteins play a crucial role in determining the specificity of vesicular transport pathways. Rab3B and Rab13 localize to tight junction in polarized epithelial cells and cytoplasmic vesicular structures in non-polarized fibroblasts, but their functions are poorly understood. Here we examined their roles in regulating the cell-surface transport of apical p75 neurotrophin receptor (p75NTR), basolateral low-density lipoprotein receptor (LDLR), and tight junctional Claudin-1 using transport assay in non-polarized fibroblasts. Overexpression of Rab3B mutants inhibited the cell-surface transport of LDLR, but not p75NTR and Claudin-1. In contrast, overexpression of Rab13 mutants impaired the transport of Claudin-1, but not LDLR and p75NTR. These results suggest that Rab3B and Rab13 direct the cell-surface transport of LDLR and Claudin-1, respectively, and may contribute to epithelial polarization.


Laser-Induced Breakdown Spectroscopy Coupled with Multivariate Chemometrics for Variety Discrimination of Soil.
The aim of this work was to analyze the variety of soil by laser-induced breakdown spectroscopy (LIBS) coupled with chemometrics methods. 6 certified reference materials (CRMs) of soil samples were selected and their LIBS spectra were captured. Characteristic emission lines of main elements were identified based on the LIBS curves and corresponding contents. From the identified emission lines, LIBS spectra in 7 lines with high signal-to-noise ratio (SNR) were chosen for further analysis. Principal component analysis (PCA) was carried out using the LIBS spectra at 7 selected lines and an obvious cluster of 6 soils was observed. Soft independent modeling of class analogy (SIMCA) and least-squares support vector machine (LS-SVM) were introduced to establish discriminant models for classifying the 6 types of soils, and they offered the correct discrimination rates of 90% and 100%, respectively. Receiver operating characteristic (ROC) curve was used to evaluate the performance of models and the results demonstrated that the LS-SVM model was promising. Lastly, 8 types of soils from different places were gathered to conduct the same experiments for verifying the selected 7 emission lines and LS-SVM model. The research revealed that LIBS technology coupled with chemometrics could conduct the variety discrimination of soil.


Pituitrin Injection before Hysteroscopic Curettage for Treating Type I Cesarean Scar Pregnancy in Comparison with Uterine Artery Embolization: A Retrospective Study.
The effectiveness and safety of pituitrin injection coupled with hysteroscopy and suction curettage as treatment for type I cesarean scar pregnancy (CSP) have not been studied enough in the literature, by comparing it to uterine artery embolization (UAE) followed by suction curettage we aim to determine its efficacy. Data of 53 patients (the PIT group) with type I CSP treated with pituitrin injection combined with hysteroscopic suction curettage and 137 patients (the UAE group) with type I CSP treated with UAE followed by suction curettage were collected in retrospect. The clinical data were analyzed statistically to compare the efficacy and safety between the two groups. The PIT group had a shorter duration of postoperative vaginal bleeding, postoperative hospitalization, and overall hospitalization length (P < 0.05). The PIT group had lower overall hospitalization costs and a lower rate of adverse events than the UAE group (P < 0.05). There was no significant difference between the two groups in terms of treatment success rate, the average length of operation, blood loss during the procedure, time when serum β-hCG returned to normal range, and menstrual recovery time after hospital release (P > 0.05). UAE and pituitrin injection followed by hysteroscopic suction curettage are good choices for type I CSP treatment. However, pituitrin injection with hysteroscopic suction curettage outperforms UAE followed by suction curettage. Thus, pituitrin injection may be an option of high priority for type I CSP.


Invertebrate vasopressin/oxytocin homologs. Characterization of peptides from Conus geographus and Conus straitus venoms.
The vasopressin-oxytocin family of peptides is of very ancient lineage, found in organisms as diverse as hydra and man. Although these peptides have been intensively studied in vertebrates, the presumably more extensive invertebrate series was defined primarily by immunological methods. In this report, we describe the purification and structures of two peptides of the vasopressin-oxytocin family from molluscs ("Conopressins"), which were found in the venom of fish-hunting marine snails of the genus Conus. The biological activity observed when the two snail peptides are injected intracerebrally into mice is very similar to that elicited by the vertebrate neurohypophyseal hormones and presumably reflects their actions upon a common receptor in the brain. The sequences of the purified peptides reveal unique features not found in the vertebrate peptide series, most notably an additional positive charge. These are the first members of the invertebrate series of the vasopressin-oxytocin family to be characterized biochemically. The sequences of these peptides are: from Conus geographus venom, Lys-conopressin-G, Cys-Phe-Ile-Arg-Asn-Cys-Pro-Lys-Gly-NH2; and from Conus striatus venom, Arg-conopressin-S, Cys-Ile-Ile-Arg-Asn-Cys-Pro-Arg-Gly-NH2.


Intramolecular 1,3-dipolar cycloaddition reactions in the synthesis of complex annelated quinolines, α-carbolines and coumarins.
In this study, we report the synthesis of several novel dihydroisoxazole-, tetrahydroisoxazole- and dihydropyrazole-fused pyrido[2,3-b]quinolines, α-carbolines, and pyrido[2,3-c]coumarins, respectively, from simple precursors and by exploring intramolecular 1,3-dipolar cycloaddition reactions involving nitrile oxides, nitrones, and nitrile imines as 1,3-dipoles.


Parent adaptation and family functioning in relation to narratives of children with chronic illness.
This study assessed the experience of parents who have a child diagnosed with chronic illness and whether children's narratives mirror these experiences. A total of 66 parents completed assessments about adaptation and family functioning. Children with type 1 diabetes or asthma participated in a story-stem narrative task. Forty-one percent of parents were unresolved about their child's diagnosis, regardless of time since diagnosis. Unresolved parents reported lower family functioning, and children in these families had more family conflict themes. Parental/Child narratives may provide unique insights into family adjustment. Future work may consider interventions related to family communication and expression of emotion.


Estrogens ameliorate remote organ inflammation induced by burn injury in rats.
The present study was designed to investigate the role of sex steroids in burn-induced remote organ injury. Male Wistar albino rats were given burn trauma (n=39), and underwent castration or sham operation at 2 h following the burn injury. Rats were injected sc with either 17beta estradiol benzoate (E2, 10 mg/kg) or an androgen receptor blocker cyproterone acetate (CPA, 25 mg/kg) or vehicle, immediately after burn and at 12 h. At 24 h of burn insult, rats were decapitated. Blood samples for RIA of testosterone, estradiol and tumor necrosis factor (TNF)-alpha and the tissue samples for myeloperoxidase activitiy (MPO) were taken. ANOVA student's t test was used for statistical analysis. Castration, antiandrogen and E2 treatments increased plasma estradiol levels and depressed burn-induced elevation in serum TNF-alpha levels. In the liver and lung, burn-induced increase in MPO was reduced by E2 and castration, while CPA was effective in reducing neutrophil infiltration only in the liver. We propose that treatment with estrogens or antiandrogens might be applicable in clinical situations to ameliorate systemic inflammation induced by burn.


Chronic apical periodontitis exacerbates atherosclerosis in apolipoprotein E-deficient mice and leads to changes in the diversity of gut microbiota.
To investigate the impact of chronic apical periodontitis (CAP) on atherosclerosis and gut microbiota by establishing a Porphyromonas gingivalis (P. gingivalis)-induced CAP in an apolipoprotein E-deficient (apoE-/- ) mice model. Twenty-eight male apoE-/- mice were divided into two groups with 14 in each: CAP group and control group. In the CAP group, sterile cotton wool containing 108 colony-forming units of P. gingivalis was placed into the pulp chamber after pulp exposure followed by coronal resin filling in bilateral maxillary first and second molars. The mice were fed with a chow diet to induce atherosclerosis. Animals were euthanized 16 weeks after the operation, and the periapical lesions of bilateral maxillary first and second molars were assessed by micro-CT. After collection of aortic arches, atherosclerotic lesions were measured by Oil Red O staining. Serum levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) were measured. Stools were collected to detect alterations in gut microbiota by 16S rRNA gene sequencing. Independent samples t-test was used to calculate the difference between the two groups. CAP was observed in 98.2% of molars. A significant increase in atherosclerotic plaque formation in the aortic arches was found in the CAP groups (CAP: 2.001% ± 0.27%, control: 0.927% ± 0.22%, p = .005). No significant difference was observed between sevum level of HDL-C (CAP: 2.295 ± 0.31 mmol/L, Control: 3.037 ± 0.55 mmol/L, p = .264) or LDL-C (CAP: 17.066 ± 3.95 mmol/L, Control: 10.948 ± 1.69 mmol/L, p = .177) in CAP group and Control group. There were no significant differences in TG (CAP: 1.076 ± 0.08 mmol/L, control: 1.034 ± 0.13 mmol/L, p = .794) or TC (CAP: 6.372 ± 0.98 mmol/L, control: 6.679 ± 0.75 mmol/L, p = .72) levels between the two groups (p > .05). The alpha diversity was elevated in the CAP group. In terms of beta diversity, the CAP and control groups were clearly distinguished by the microbial community. In a mouse experimental model, pulp infection with P. gingivalis -induced CAP, thus aggravating the development of atherosclerosis. Meanwhile, CAP increased alpha diversity and altered the beta diversity of the gut microbiota.