Basic bioengineering concepts. Concepts in bone performance, failure, and osteosynthesis.
The basic concept of engineering applied to the biomechanical performance behavior of solids has been presented. Areas of conceptual disagreement in bone failure loading modes have been indicated and provide an excellent area for continuing investigation by the podiatric surgeon. Special application to bone tissue has been emphasized with several examples of functional loading seen in podiatric performance. The underlying requirements for primary bone union by the production of absolute stability have been discussed and some of the present problems with the use of A-O in podiatric surgery have been suggested.


Cultural competence education for health professionals from pre-graduation to licensure delivered using facebook: Twelve-month follow-up on a randomized control trial.
Cultural competence (CC) training is widely recognized as a crucial component of the professional development of healthcare providers. There is no study on the effect of Facebook (FB) as a strategy to promote continual learning to enhance CC among students in health professions. To test the effects of cultural competence education using FB as a delivery platform on knowledge, awareness, self-efficacy, and skill related to CC in health students from pre-graduation to licensed professional stages. A randomized controlled trial. We recruited students from professional nursing, pharmacy, and nutrition programs at six medical universities and randomly assigned them to study groups. Between T1 and T2 (months 1-3), the intervention group (IG) received pre-graduation education in CC while the control group (CG) received their regular educational program. Between T2 and T3 (months 6-9), IG received on-the-job education in CC while CG received the regular program. An online self-report questionnaire assessing CC knowledge, awareness, self-efficacy, and skill was analyzed at baseline, 6months, and 12months. Of 180 participants who completed the pretest, 120 (65 IG and 55 CG) completed both follow-ups. Changes over time were mixed; the only statistical difference between groups was an improvement in awareness in IG but not in CG. At 12months, intervention and control participants had different levels of awareness of CC (β=2.56, p<0.001), but other outcomes did not differ between groups. Health profession educators can adopt Facebook as an education delivery platform to offer personalized, social learning incorporating cultural competency curricula into ongoing education and training in rising awareness on CC.


Aging mechanism as the "down side" of adaptation: a network approach.
Many diverse hypotheses on aging are in play. All from "aging genes" over decreasing telomere length to increased level of gene mutations has been suggested to determine an organism's lifespan, but no unifying theory exists. As part of a growing interest toward more integrative approaches in the field we propose a simplistic model based on the "use-it-or-lose-it" concept: we hypothesize that biological aging is a systemic property and the down side of adaptation in complex biological networks at various levels of organization: from brain over the immune system to specialized tissues or organs. The simple dynamical model undergoes three phases during its lifetime: (1) general plasticity (childhood), (2) optimization/adaptation to given conditions (youth and adolescence) and (3) steady state associated with high rigidity (aging). Furthermore, our model mimics recent data on the dynamics of the immune system during aging and, although simplistic, thus captures essential characteristics of the aging process. Finally, we discuss the abstract model in relation to current knowledge on aging and propose experimental setups for testing some of the theoretical predictions.


The electrochemical preparation of FAD/ZnO with hemoglobin film-modified electrodes and their electroanalytical properties.
Flavin adenine dinucleotide (FAD)-modified zinc oxide self-assembly films were prepared using repeated cyclic voltammetry. The electrochemical reaction of the hemoglobin with the FAD/ZnO self-assembly film-modified electrodes and their electrocatalytic properties were investigated. This paper describes the successful loading of the electrochemically active molecules of hemoglobin and FAD along with ZnO by electrochemical method. In addition to the cyclic voltammetry, an electrochemical quartz crystal microbalance was used to study the growth mechanism and the properties of the films. The FAD/zinc oxide films exhibited a single redox couple, which corresponded to the FAD redox couple. The electrocatalytic properties of the O2, H2O2, trichloroacetic acid and SO(3)2- were studied by the FAD/zinc oxide films in the absence or in the presence of hemoglobin. The electrocatalytic reduction current had been developed from the cathodic peak of the FAD/zinc oxide redox couple. The electrocatalytic process involved an interaction of hemoglobin and FAD/GC film-modified electrode to increase the electrocatalytic reduction current. The electrocatalytic reduction of O2 using the FAD/zinc oxide films was investigated by cyclic voltammetry and rotating ring-disk electrode methods.


Two new species of cricket genus Anaxiphomorpha Gorochov, 1987 (Orthoptera, Trigonidiidae, Trigonidiinae) in China.
Two new species, Anaxiphomorphanonggangensis sp. nov. and Anaxiphomorphamanereserratus sp. nov., are reported from Guangxi Province, China. Descriptions and illustrations for the new species and a key to all known species of Anaxiphomorpha are provided.


Diurnal H-reflex variation in mice.
Mice exhibit diurnal variation in complex motor behaviors, but little is known about diurnal variation in simple spinally mediated functions. This study describes diurnal variation in the H-reflex (HR), a wholly spinal and largely monosynaptic reflex. Six mice were implanted with tibial nerve cuff electrodes and electrodes in the soleus and gastrocnemius muscles, for recording of ongoing and nerve-evoked electromyographic activity (EMG). Stimulation and recording were under computer control 24 h/day. During a 10-day recording period, HR amplitude varied throughout the day, usually being larger in the dark than in the light. This diurnal HR variation could not be attributed solely to differences in the net ongoing level of descending and segmental excitation to the spinal cord or stimulus intensity. HRs were larger in the dark than in the light even after restricting the evoked responses to subsets of trials having similar ongoing EMG and M-responses. The diurnal variation in the HR was out of phase with that reported previously for rats, but was in phase with that observed in monkeys. These data, supported by those in other species, suggest that the supraspinal control of the excitability of the HR pathway varies throughout the day in a species-specific pattern. This variation should be taken into account in experimental and clinical studies of spinal reflexes recorded at different times of day.


Analysis of matched primary and recurrent BRCA1/2 mutation-associated tumors identifies recurrence-specific drivers.
Recurrence is a major cause of death among BRCA1/2 mutation carriers with breast (BrCa) and ovarian cancers (OvCa). Herein we perform multi-omic sequencing on 67 paired primary and recurrent BrCa and OvCa from 27 BRCA1/2 mutation carriers to identify potential recurrence-specific drivers. PARP1 amplifications are identified in recurrences (False Discovery Rate q = 0.05), and PARP1 is significantly overexpressed across primary BrCa and recurrent BrCa and OvCa, independent of amplification status. RNA sequencing analysis finds two BRCA2 isoforms, BRCA2-201/Long and BRCA2-001/Short, respectively predicted to be sensitive and insensitive to nonsense-mediated decay. BRCA2-001/Short is expressed more frequently in recurrences and associated with reduced overall survival in breast cancer (87 vs. 121 months; Hazard Ratio = 2.5 [1.18-5.5]). Loss of heterozygosity (LOH) status is discordant in 25% of patient's primary and recurrent tumors, with switching between both LOH and lack of LOH found. Our study reveals multiple potential drivers of recurrent disease in BRCA1/2 mutation-associated cancer, improving our understanding of tumor evolution and suggesting potential biomarkers.


Using within-subject pattern classification to understand lifespan age differences in oscillatory mechanisms of working memory selection and maintenance.
In lifespan studies, large within-group heterogeneity with regard to behavioral and neuronal data is observed. This casts doubt on the validity of group-statistics-based approaches to understand age-related changes on cognitive and neural levels. Recent progress in brain-computer interface research demonstrates the potential of machine learning techniques to derive reliable person-specific models, representing brain behavior mappings. The present study now proposes a supervised learning approach to derive person-specific models for the identification and quantification of interindividual differences in oscillatory EEG responses related to working memory selection and maintenance mechanisms in a heterogeneous lifespan sample. EEG data were used to discriminate different levels of working memory load and the focus of visual attention. We demonstrate that our approach leads to person-specific models with better discrimination performance compared to classical person-nonspecific models. We show how these models can be interpreted both on an individual as well as on a group level. One of the key findings is that, with regard to the time dimension, the between-person variance of the obtained person-specific models is smaller in older than in younger adults. This is contrary to what we expected because of increased behavioral and neuronal heterogeneity in older adults.


IGF-1 increases survival of CD4+ lineage in a 2D model of thymocyte/thymic stromal cell co-culture.
Insulin-like growth factor-1 (IGF-1), in addition to its classic effects on cell proliferation and organism growth, has pleiotropic actions on the immune system, particularly on the thymus. Thus, the objective of this study was to evaluate the influence of IGF-1 on molecules involved in the survival of thymocytes in vitro using a co-culture system with thymic stromal cells obtained from C57BL/6 mice. The obtained thymic stroma has contained thymic epithelial cells, macrophages, dendritic cells, fibroblasts, and preserved the expression of the major histocompatibility complex (MHC) molecules. Fresh thymocytes were added to these cultures and the co-culture were treated daily with IGF-1 (100 ng/mL) for 3 days. In this scheme, the viability of the thymocytes was about 70%, either in the control (non-treated cells) or in the IGF-1-treated cultures. It was found that IGF-1 was able to increase the percentage of thymocytes from the CD4+ single-positive (SP) subset. This result was accompanied by an increase in the MHC II expression on thymic stromal cells and an augment on the interleukin-7 receptor (CD127) on the surface of the CD4 SP thymocytes after treatment with IGF-1. Finally, IGF-1 treatment increased the expression of the ThPOK encoding gene Zbtb7b, which is involved in the differentiation of CD4+ SP thymocytes. Our study demonstrates the participation of IGF-1 in the thymocyte/thymic stroma interactions, especially in the extended survival of the CD4+ lineage in the thymus.


Centrally administered tumor necrosis factor-alpha facilitates the avoidance performance of Sprague-Dawley rats.
In addition to their immunological functions, recent research has indicated that the pro-inflammatory cytokines can influence learning and memory processes. We have previously shown that a peripheral injection of TNFalpha facilitates the acquisition of a leverpress avoidance task 24 h post-injection. Because the improved acquisition is presumably mediated by central changes, the current experiment involved directly injecting TNFalpha into the third ventricle 24 h prior to training. The data indicate that low (20 ng) but not high (40 ng) doses of TNFalpha produced improved avoidance performance. Results are discussed in terms of possible monoaminergic sensitization induced by TNFalpha and the relationship of this to acquisition of the avoidance response.


Effectiveness of Immediate Video-Assisted Thoracoscopic Surgery for Empyema: A Multicentre, Retrospective Cohort Study.
Because of limitations in previous randomised controlled trials and observational studies, the effectiveness of immediate video-assisted thoracoscopic surgery (VATS) for patients with empyema in real-world settings remains unclear. This study aimed to evaluate whether immediate VATS improves clinical outcomes in patients with empyema. This multicentre retrospective cohort study included 744 patients with physician-diagnosed empyema from six hospitals between 2006 and 2021. The exposure was VATS performed within 3 days of empyema diagnosis, the primary outcome was 30-day mortality, and secondary outcomes were 90-day mortality, length of hospital stay, and time from diagnosis to discharge. We used propensity score weighting to account for potential confounders. For outcome analyses, we used logistic regression for mortality outcomes and gamma regression for the number of days. Among the 744 patients, 53 (7.1%) underwent VATS within 3 days, and 691 (92.9%) initially received conservative treatment. After propensity score weighting, the differences in 30- and 90-day mortalities between the immediate VATS and initial conservative treatment groups were 1.18% (95% confidence interval [CI], -10.7 to 13.0%) and -0.08% (95% CI, -10.3 to 10.2%), respectively. The differences in length of hospital stay and time from diagnosis to discharge were -3.22 (95% CI, -6.19 to -0.25 days) and -5.04 days (95% CI, -8.19 to -1.90 days), respectively. Our real-world study showed that immediate VATS reduced the length of hospital stay and the time from diagnosis to discharge. Considering the small sample and differences in protocols between countries, further large-scale studies are warranted.


Capacitance sensing drop counter.
A simple and inexpensive capacitive sensor which fits around any normal drip chamber has been devised. When it is made part of a suitable AC bridge circuit, the small changes in capacitance caused by the presence of a drop between the sensor plates can be reliably detected. The sensor is insensitive to its position on the drip chamber or to tilt of the chamber and unlike optical drop sensors, it is insensitive to ambient lighting.


Kinematic covariation in pediatric, adult and elderly subjects: is gait control influenced by age?
In human walking, kinematics of lower limb segments covary. Our objective was to assess the impact of age at different speeds (slow, medium and fast) on kinematic segmental covariation in normal subjects. Thirty subjects ranged into 6 age groups ("5 years", "10 years", "15 years", "20 years" and "70 years") were included. We performed a gait analysis on a treadmill at 3 predetermined speeds: 1 (slow), 3 (medium) and 5 (fast) km h(-1), except for the 5 years group who was unable to walk at 5 km h(-1). Kinematic segmental covariation was computed and represented by a 3D-loop, described by a principal component analysis (Borghese's methodology). We studied the percentage of variance of each component of the principal component analysis, knowing that the percentage of variance of the first and the second components reflected the shape of the loop, and that the percentage of variance of the third component was an index of its planarity. The effect of age was tested using a one-way analysis of variance. When comparing the age groups at the same speed, we found a significant difference in the percentage of variance of the first and the second components between the 5 and the 10 years at 3 km h(-1). We also noticed a difference in the percentage of variance of the third component at 5 km h(-1) between the 10 years and the 15 and 20 years groups. We observed that kinematic covariation remains stable throughout adulthood between 15 and 70 years old at slow, medium and fast speed. In children, a mature percentage of variance of the first and the second components is acquired from 10 years old and a mature percentage of variance of the third component from 15 years old.


Antidepressant drugs for narcolepsy.
Narcolepsy is a disorder of the central nervous system, the main symptoms of which are excessive daytime sleepiness (EDS) and cataplexy (an abrupt and reversible decrease in or loss of muscle tone, affecting the limbs and/or trunk, elicited by emotional stimuli). Narcolepsy has an adverse impact on people's quality of life. Together with stimulant drugs (used to control EDS), antidepressants are usually recommended to counteract cataplexy. In addition, some antidepressants are also reported to improve EDS. To evaluate the effects of antidepressant drugs on EDS, cataplexy, quality of life, and their side effects in people with narcolepsy. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), PsycINFO (1872 to 2003), and CINAHL (1981 to 2003). Bibliographies of identified articles were reviewed to find additional references. Unpublished randomised trials were searched for by consulting governmental and non-governmental clinical trial registers, disease-specific websites, investigators and experts in the field, pharmaceutical companies/manufacturers. Parallel or cross-over randomised or quasi-randomised controlled trials testing the treatment of narcolepsy with any type of antidepressant drug versus no treatment, placebo, or another antidepressant drug. Two reviewers independently selected trials for inclusion and extracted data. Outcomes were: (a) elimination of EDS; (b) mean reduction of EDS; (c) elimination of cataplexy; (d) 50% or greater reduction in cataplexy frequency; (e) mean reduction of cataplexy; (f) mean improvement in quality of life; (g) adverse events; (h) withdrawal from treatment. Two cross-over trials were included. The methodological quality of both studies was unclear and so the influence of common biases was impossible to define. As the trials tested two different comparisons (one femoxetine versus placebo, the other fluvoxamine versus clomipramine) meta-analysis was not performed. In the first trial (10 participants) femoxetine had no significant effect in eliminating or reducing EDS; a significant reduction of cataplexy was in favour of femoxetine. Mild and transient side effects were reported in the femoxetine treatment period by two participants. In the second trial the authors inappropriately treated the trial design as a parallel study and no conclusions can be reached in favour of either drug. There was no good quality evidence that antidepressants are effective for narcolepsy or improve quality of life. Despite the clinical consensus recommending antidepressants for cataplexy there is scarce evidence that antidepressants have a positive effect on this symptom. There is a clear need for well-designed randomised controlled trials to assess the effect of antidepressants on narcolepsy.


Alisol B blocks the development of HFD-induced obesity by triggering the LKB1-AMPK signaling in subcutaneous adipose tissue.
As a global epidemic disease, obesity causes dysfunction of glucose and lipid metabolism leading to persistently high morbidity and mortality. Given the difficulty to achieve and maintain weight loss through controlling diet and physical exercise, pharmacotherapy is considered an effective treatment for obesity. This investigation revealed that alisol B, a triterpene monomer isolated from the classical Chinese medicine Alisma orientale (Sam.) Juzep, functioned in suppressing adipogenesis and reducing the mass of subcutaneous adipose tissue, resulting in the reduction of weight gain, and improvements of hyperglycemia, hyperlipidemia, and insulin resistance in HFD-induced obese mice. In consistent to the results, alisol B also significantly inhibited adipocyte differentiation and maturation in vitro. Furthermore, our data revealed that the effects of alisol B on adipogenesis were mediated by LKB1-AMPK signaling pathway. In total, alisol B could be a potential lead compound which contributes to the improvement of obesity-related metabolic disorders.


Congenital membranous colonic stenosis--case report of an extremely rare anomaly.
Congenital colonic stenosis is a rare anomaly. Congenital membranous colonic stenosis is more rare. The authors experienced a case of congenital membranous colonic stenosis that was diagnosed and treated successfully. To the authors' knowledge, congenital membranous colonic stenosis has not been reported previously in the literature.


Antioxidant defense in quiescent cells determines selectivity of electron transport chain inhibition-induced cell death.
Mitochondrial electron transport chain (ETC) targeting shows a great promise in cancer therapy. It is particularly effective in tumors with high ETC activity where ETC-derived reactive oxygen species (ROS) are efficiently induced. Why modern ETC-targeted compounds are tolerated on the organismal level remains unclear. As most somatic cells are in non-proliferative state, the features associated with the ETC in quiescence could account for some of the specificity observed. Here we report that quiescent cells, despite increased utilization of the ETC and enhanced supercomplex assembly, are less susceptible to cell death induced by ETC disruption when glucose is not limiting. Mechanistically, this is mediated by the increased detoxification of ETC-derived ROS by mitochondrial antioxidant defense, principally by the superoxide dismutase 2 - thioredoxin axis. In contrast, under conditions of glucose limitation, cell death is induced preferentially in quiescent cells and is correlated with intracellular ATP depletion but not with ROS. This is related to the inability of quiescent cells to compensate for the lost mitochondrial ATP production by the upregulation of glucose uptake. Hence, elevated ROS, not the loss of mitochondrially-generated ATP, are responsible for cell death induction by ETC disruption in ample nutrients condition, e.g. in well perfused healthy tissues, where antioxidant defense imparts specificity. However, in conditions of limited glucose, e.g. in poorly perfused tumors, ETC disruption causes rapid depletion of cellular ATP, optimizing impact towards tumor-associated dormant cells. In summary, we propose that antioxidant defense in quiescent cells is aided by local glucose limitations to ensure selectivity of ETC inhibition-induced cell death.


Design, synthesis and biological evaluation of novel spiro-quinazolinone derivatives as chitin synthase inhibitors and antifungal agents.
A series of spiro-quinazolinone scaffolds were constructed based on the bioactivity of quinazolinone and the inherent feature of spirocycle to design novel chitin synthase inhibitors that possess mode of action different from that of the currently used antifungal agents. Among them, the spiro[thiophen-quinazolin]-one derivatives containing α, β-unsaturated carbonyl fragments had shown inhibitory activities against chitin synthase and antifungal activities. The enzymatic experiments showed that among the sixteen compounds, compounds 12d, 12g, 12j, 12l and 12m exhibited inhibitions against chitin synthase with IC50 values of 116.7 ± 19.6 μM, 106.7 ± 14.2 μM, 102.3 ± 9.6 μM, 122.7 ± 22.2 μM and 136.8 ± 12.4 μM, respectively, which were comparable to that of polyoxin B (IC50 = 93.5 ± 11.1 μM). The assays of enzymatic Kinetic parameters showed that compound 12g was a non-competitive inhibitor of chitin synthase. The antifungal assays showed that compounds 12d, 12g, 12j, 12l and 12m exhibited a broad-spectrum of antifungal activity against the four strains tested in vitro. In which, compounds 12g and 12j had stronger antifungal activity against four tested strains than that of polyoxin B and similar to that of fluconazole, while compounds 12d, 12l and 12m showed antifungal activity comparable to that of polyoxin B against four tested strains. Meanwhile, compounds 12d, 12g, 12j, 12l and 12m exhibited good antifungal activity against fluconazole-resistant and micafungin-resistant fungi variants with MIC values ranging from 4 to 32 μg/mL while the MIC values of reference drugs were above 256 μg/mL. Furthermore, the results of drug-combination experiments showed that compounds 12d, 12g, 12j, 12l and 12m had synergistic or additive effects with fluconazole or polyoxin B. The results of sorbitol protection experiment and the experiment of antifungal activity against micafungin-resistant fungi further demonstrated that these compounds target chitin synthase. The result of cytotoxicity assay showed that compound 12g had low toxicity toward human lung cancer A549 cells and the ADME analysis in silico displayed that compound 12g possessed promising pharmacokinetic properties. The molecular docking indicated that compound 12g formed multiple hydrogen bond interactions binding to chitin synthase, which might be conductive to increasing the binding affinity and inhibiting the activity of chitin synthase. The above results indicated that the designed compounds were chitin synthase inhibitors with selectivity and broad-spectrum antifungal activity and could be act as the lead compounds against drug-resistant fungi.


Organocatalysis Combined with Photocatalysis.
Over the past decade, the combination of visible light photocatalysis and organocatalysis has made remarkable progress in modern chemical synthesis. In these dual catalysis system, photocatalysts or photosensitizers absorb visible light to induce their photoexcited states which can activate unreactive substrates via electron or energy transfer mechanisms, and organocatalysts are usually employed to regulate the chemical reactivity of the other substrates. By doing so, two reactive species react with each in a selective-especially enantioselective-way, to provide the final products. This article summarizes the recent development of cooperative catalysis by the combination of organocatalysis and photocatalysis in asymmetric organic synthesis. These reactions are classified according to the manner of activation of the organocatalysts. Enamine/iminium catalysts are used to activate unreactive carbonyl molecules. Nucleophilic catalysts including nitrogen heterocycle carbene catalysts and tertiary amine catalysts are employed to reverse the reactivity of electrodeficient substrates including aldehydes and enals. Chiral Brønsted acid catalysts are used to activate substrates by forming key H-bonding complexes between substrates and catalysts.


Dietary quality among Tehranian adults in relation to lipid profile: findings from the Tehran Lipid and Glucose Study.
The prevalence of dyslipidaemia has been increasing in developing countries that are undergoing nutrition transition. However, the association of diet quality and lipid profile has not been well-understood in these countries. The aim of the current study was to compare the ability of three diet quality indices--the Mediterranean diet scale (MDS), healthy eating index-2005 (HEI-2005), and diet quality index-international (DQI-I) in relation to changes in lipid profile between baseline and 6.7 years of follow-up. Baseline data from two 24-hour dietary recalls provided by 469 adults with mean age of 38.7 +/- 12.3 years, who were participants of the Tehran Lipid and Glucose Study, were analyzed to describe dietary intakes. Data on anthropometry, sociodemography, physical activity, and other lifestyle variables were recorded, and a comparison of baseline and follow-up data revealed changes in the concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-G), and low-density lipoprotein cholesterol (LDL-C). A general linear model was used in assessing changes in lipid profile depending on adherence to diet quality indices at baseline, after adjustment for age, smoking status, waist-circumference, body mass index, physical activity, and energy intake. A significant interaction was observed between scores and sex, and upon stratification, males in the highest quartile score of the HEI-2005 had significantly lower TG changes than those in the lowest quartile, after adjusting for confounders (-8.8 vs 2.9, p = 0.038). No association was apparent in females (-0.2 vs 11.2, p = 0.297). In addition, a positive association was found between DQI-I and HDL-C (Q1-0.6 vs Q4 = -2.0, p = 0.044) in males. In both sexes, all these indices were weakly associated with TC while none was associated with LDL-C. It is concluded: adherence to the HEI-2005 recommendations was weakly associated with reduced TG concentration in an urban Iranian adult population. The MDS and DQI-I were not related to change in lipid profile.


Factors Related to the Intention of Israelis to Use Complementary and Alternative Medicine.
Despite the significant rise in the use of complementary and alternative medicine (CAM) in Israel, the factors affecting the decision to do so remain unclear. Thus, the purpose of the study was to explore factors that affect Israelis' intention to use CAM, using the theory of planned behavior (TPB). A quantitative correlational study. A convenience sample of 200 Hebrew-speaking Israelis aged 21+ completed a questionnaire based on the TPB. Respondents expressed moderate intention to use CAM. The TPB predictability of this intention was 57% (R2 = .57), with behavioral beliefs being the most influential factor. The family was identified as another significant factor. Previous experience with CAM was also found to raise the intention to use it in the future. When referring a patient for services of CAM, it is important to provide in-depth explanations emphasizing positive anticipated outcomes of these services in order to effect a change in the patient's behavioral beliefs. Patient's family should be considered as a possible resource to promote usage of CAM.


Development of a hybrid pollution index for heavy metals in marine and estuarine sediments.
Heavy metal pollution of sediments is a growing concern in most parts of the world, and numerous studies focussed on identifying contaminated sediments by using a range of digestion methods and pollution indices to estimate sediment contamination have been described in the literature. The current work provides a critical review of the more commonly used sediment digestion methods and identifies that weak acid digestion is more likely to provide guidance on elements that are likely to be bioavailable than other traditional methods of digestion. This work also reviews common pollution indices and identifies the Nemerow Pollution Index as the most appropriate method for establishing overall sediment quality. Consequently, a modified Pollution Index that can lead to a more reliable understanding of whole sediment quality is proposed. This modified pollution index is then tested against a number of existing studies and demonstrated to give a reliable and rapid estimate of sediment contamination and quality.


Outcome of self-reported functional-somatic symptoms in a community sample of adolescents.
It is unclear if functional-somatic symptoms in adolescents increase the risk for future psychiatric disorders. Therefore, the outcome and continuity of adolescent self-reported functional-somatic symptoms in young adulthood were assessed. Self-reported data on functional-somatic symptoms from an ongoing epidemiological study in children started in 1983 were analyzed. Participants were adolescents aged 11-18 who filled out standardized questionnaires in 1989 and 1991 and who were reassessed in 1997 when they were young adults between ages 19 and 26. Outcome measures were research psychiatric diagnoses and self-reported functional-somatic symptoms in 1997. Functional-somatic symptoms were associated with other measures of psychopathology in adolescents. Adolescents with specific functional-somatic symptoms tended to report the same symptom along with other symptoms at follow-up. Adolescent self-reported functional-somatic symptoms did not increase the risk for future psychiatric disorders. Young adults with functional-somatic complaints were diagnosed more often than controls with depressive disorders and anxiety disorders, but not with antisocial personality disorders and substance use disorders. Adolescent self-reported functional-somatic symptoms were common and enduring but were not predictive for psychiatric disorders in young adulthood. Adolescents and young adults who complain of multiple functional-somatic complaints should be assessed for the presence of a psychiatric disorder particularly depression or anxiety.


Impact of first contact on symptom onset-to-door time in patients presenting for primary percutaneous coronary intervention.
To determine effect of first medical contact type on symptom onset-to-door time (SODT). Shorter total ischemic time is associated with improved outcomes in ST-elevation myocardial infarction. From 2005 to 2009, we reviewed records of all consecutive patients treated with primary percutaneous coronary intervention for ST-elevation myocardial infarction at our tertiary care teaching hospital (median follow-up 3.85 years). We compared SODT in patients whose first medical contact was a private physician (in person or via telephone) vs patients who presented to the emergency department (ED) directly (in person or via Emergency Medical Services). Of 366 patients, 84 (23%) contacted a physician (group A) while 282 (77.6%) did not (group B). Group A had higher median SODT (239.5 vs 130 minutes, P = .0043) and significantly higher mortality (log rank P = .0392, Cox Proportional Hazard Model risk factors: physician contact first [P < .013], age [P < .0001] and peripheral vascular disease [P < .035]). Two factors associated with prolonged SODT: (1) contacting a physician first P = .002 and (2) personal mode of transportation, P = .002. Patients presenting during "on-hours" (weekdays) were more likely to first contact a physician compared with those presenting during "off-hours" (weeknights and weekends) (66.67% in group A vs 45.04% in group B, P < .001). Patients whose first medical contact was a physician had greater pre-hospital delays and worse survival compared to those who sought emergent medical care directly. This pattern occurred more often during "on-hours." Educational efforts aimed at both patient and physician office practices are warranted.


Calprotectin can play an inflammatory role in acne vulgaris.
Acne vulgaris (AV) is a chronic inflammatory disorder of the pilosebaceous unit. Although various mechanisms have been indicated in the etiopathogenesis of acne vulgaris, the exact pathophysiology is still unknown. To investigate the level of calprotectin in acne vulgaris and its levels relationship with disease severity. A total of 66 AV patients, who were divided into 33 mild and 33 moderate-severe cases, and 30 healthy controls were enrolled in the study. Disease severity was assessed using the Global Acne Score. According to this scale, patients whose Global Acne Score was 1-18 had mild acne, those with a score of 19-30 had moderate acne, those with a score of 31-38 had severe acne, and those with a score greater than 39 had very severe acne. Serum calprotectin levels of all participants were measured by enzyme-linked immunosorbent assay method. The serum calprotectin levels in the moderate-severe AV group were significantly higher than that of the mild AV group (p < 0.001). In addition, the serum calprotectin level in the mild AV group was significantly higher than that of the healthy control group (p = 0.047). However, in the Spearman's correlation analysis, the serum calprotectin level and GAS were not correlated in AV patients (p = 0.171, r = 0.179). Serum calprotectin levels are increased in mild and moderate AV patients.


1H MR spectroscopy monitoring of changes in choline peak area and line shape after Gd-contrast administration.
Fifteen percent loss in the peak area of choline containing compounds (Cho) was recently observed in 1H MR spectra of contrast-enhancing tumor at 5-10 min after Gd-contrast administration [Magn. Reson. Med. 37:222-225, 1997]. In this study, chemical shift imaging (CSI, 1500/135 ms PRESS) was used to assess the spectral changes in 47 Gd-enhancing glial brain tumors and metastatic brain tumors measured at 0-5, 5-10, and/or 10-15 min after administration of Gd-contrast. Percent Cho peak area losses measured at these times, 3 +/- 3, 12 +/- 2, and 14 +/- 3 SEM, respectively, coincided with trends of line narrowing and up-field shift of the Cho peak. Significant changes in creatine and N-acetyl acetate signals were not observed. It is concluded that the Gd-induced loss of tumor Cho signal measured after 5 min, typically required for post contrast-MRI and the positioning of the CSI volume on tumor, shows little further change with time, if any.


Progesterone receptors in the female lower urinary tract.
When female estrogenized rabbits were injected i.v. with 3H-progesterone, the tritium concentration determined after one hour was about two to three times higher in urethra, urinary bladder and vagina than in the heart. High affinity progesterone receptors (KD = 1-2 nM) could be demonstrated in both cytoplasmic and nuclear fractions prepared from estrogenized rabbit urethra, bladder and vagina. The cytosolic receptor concentration in both urethra and bladder was about half of that in the vagina. The concentration of nuclear receptors in urethra was not significantly different from that in the vagina, but in the bladder the concentration was only about one fourth of that in the vagina or urethra. The mean KD of cytosolic receptors from bladder was significantly higher than the corresponding values in urethra and vagina. Progesterone binding sites in the bladder had a broader hormonal specificity than those in the urethra or vagina. The present demonstration of specific progesterone receptors in the female urethra might provide a possible link between estrogen progesterone interaction and the appearance of urinary incontinence during pregnancy in women.


Inhibition of phosphorylated calcium/calmodulin-dependent protein kinase IIα relieves streptozotocin-induced diabetic neuropathic pain through regulation of P2X3 receptor in dorsal root ganglia.
Diabetic neuropathic pain (DNP) is frequent among patients with diabetes. We previously showed that P2X3 upregulation in dorsal root ganglia (DRG) plays a role in streptozotocin (STZ)-induced DNP but the underlying mechanism is unclear. Here, a rat model of DNP was established by a single injection of STZ (65 mg/kg). Fasting blood glucose was significantly elevated from the 1st to 3rd week. Paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) in diabetic rats significantly reduced from the 2nd to 3rd week. Western blot analysis revealed that elevated p-CaMKIIα levels in the DRG of DNP rats were accompanied by pain-associated behaviors while CaMKIIα levels were unchanged. Immunofluorescence revealed significant increase in the proportion of p-CaMKIIα immune positive DRG neurons (stained with NeuN) in the 2nd and 3rd week and p-CaMKIIα was co-expressed with P2X3 in DNP rats. KN93, a CaMKII antagonist, significantly reduce mechanical hyperalgesia and thermal hyperalgesia and these effects varied dose-dependently, and suppressed p-CaMKIIα and P2X3 upregulation in the DRGs of DNP rats. These results revealed that the p-CaMKIIα upregulation in DRG is involved in DNP, which possibly mediated P2X3 upregulation, indicating CaMKIIα may be an effective pharmacological target for DNP management.


One-stage operation for esophageal perforation of a thoracic aortic aneurysm.
The patient was a 65-year-old man. Preoperative computed tomography showed a ruptured thoracic aortic aneurysm that formed a submucosal hematoma in the thoracic esophagus with perforation near the esophageal-cardiac junction. A one-stage operation was performed. The aortic arch and proximal descending aorta were replaced with rifampicin-soaked synthetic grafts, followed by subtotal esophagectomy with primary reconstruction using a gastric tube. His early postoperative course was uneventful, and he started oral intake on postoperative day (POD) 15; however, dysphagia occurred on POD 20, and an esophageal fistula and mediastinitis developed more than 1 month after the operation. The patient recovered from mediastinitis after 4 months of mediastinal drainage and administration of antibiotics. Thus, a one-stage operation for esophageal perforation of a ruptured thoracic aortic aneurysm with primary esophageal reconstruction is possible in selected patients. Care must be taken to avoid postoperative compression of the reconstructed esophagus by a mediastinal hematoma.


Surgical treatment of gastric outlet obstruction due to gastroduodenal tuberculosis.
Gastroduodenal tuberculosis is a very rare location of abdominal tuberculosis; it is usually secondary to pulmonary tuberculosis and is often associated with HIV infection. We report a case of a 45-year-old woman with no HIV infection and no evidence of pulmonary tuberculosis, with a history of duodenal ulcer treated for several months, who presented at the emergency department with severe gastric outlet obstruction of recent onset caused by ulcerohypertrophic antroduodenal tuberculosis. The lesion was misdiagnosed at endoscopy as a malignancy, although histological examination of biopsies showed only chronic inflammation. The diagnosis was established at surgery, when a frozen section of an enlarged lymph node showed the presence of giant cells and caseating granuloma. The treatment was gastric resection with Roux-en-Y gastrojejunal anastomosis. In this patient the rare gastroduodenal location of tuberculosis occurred as primary disease in the absence of other organ involvement.


Immunomorphologic characterization of chicken thrombocytes.
Chicken thrombocytes were enriched for immunization by utilizing their strong capacity to adhere to plastic surfaces. The produced rabbit anti-thrombocyte serum ATS 3 reacted by means of the unlabeled antibody enzyme method (PAP) specifically with thrombocytes of fixed chicken-blood smears, but not with lymphocytes or other blood cells. When ATS 3 (substrate diaminobencidinetetra-hydrochloride = DAB) and a 1.1 mixture of an anti-bursa serum and anti-thymus serum (ABS/ATS; substrate 4-chloro-1-naphthol = 4-Cl-1-N) were used simultaneously, thrombocytes revealed the brown color typical for DAB, whereas lymphocytes showed the blue stain of 4-Cl-1-N. The finding of a thrombocyte surface antigen not shared by lymphocytes is regarded as a further proof of the diversity of both cell systems, i.e., for the existence of a genuine thrombocyte system in chickens.


Specific method for determination of OSI-774 and its metabolite OSI-420 in human plasma by using liquid chromatography-tandem mass spectrometry.
A new simple and specific method was developed and validated for the quantitative determination of OSI-774 (Tarceva, Erlotinib) and its metabolite, OSI-420, in human plasma. Sample pretreatment involved a single protein precipitation step with acetonitrile. The analytes were separated on Waters X-Terra C(18) (50 x 2.1 mm I.D., 3.5 microm) analytical column and eluted with acetonitrile-water mobile (70:30, v/v) containing 0.1% formic acid. The analytes of interest were monitored by tandem mass spectrometry with electrospray positive ionization. The overall extraction efficiency was greater than 88% for OSI-774 and 62% for OSI-420, with values for within-day and between-day precision and accuracy of <15%. Compared to previous assays, this method is simple, specific, and reproducible and will be used to characterize the plasma pharmacokinetics of OSI-774 at doses of 50 to 150 mg to optimize treatment with this agent.


Biomarkers in an invasive fish species, Oreochromis niloticus, to assess the effects of pollution in a highly degraded Brazilian River.
Paraiba do Sul watershed is one of the most important Brazilian water bodies (5.5 million people depend on the river). It is in a critical environmental situation, polluted by industrial discharges, non-treated urban wastes, and pesticides, which have had cumulatively negative effects. This study analyzes the effects of pollution, with a biomarker approach, by using the invasive fish species, Oreochromis niloticus, as a sentinel species. The approach comprehends a general biomarker of the health of individual fish, the condition factor, a biomarker of genotoxicity, the micronuclei test; and specific biomarkers of contaminant exposure such as metallothionein (MT) and acetylcholinesterase (AChE) activity. The results revealed different effects in fish from diverse locations with varying degrees of pollution. Low AChE activities were found in fish from the region with strong agriculture activity, showing the effects of pesticides. Fish from an industrialized and heavily environmentally degraded area presented high levels of MT and low AChE activities, indicating an intricate polluted condition. It is noteworthy that fish located just upstream of the main water-treatment plant of the metropolitan area Rio de Janeiro presented high levels of MT, showing to be affected by metals. This can be an alert to public health officials. O. niloticus has proven a suitable sentinel species to assess the effects of pollutions in an aquatic system with a complex and serious polluted situation. The present study also shows the usefulness of integrating a set of biomarkers to define the exposure and the effects of anthropogenic inputs among impacted and reference sites in this water body.


Adaptive changes in hypercapnic ventilatory response during training and detraining.
To confirm the effects of physical training and detraining on CO2 chemosensitivity, we followed hypercapnic ventilatory response at rest in the same five subjects during pre-, post- and detraining for 6 years. They joined our university badminton teams as freshmen and participated regularly in their team's training for about 3 h a day, three times a week, for 4 years. After that they retired from their teams and stopped training in order to study in the graduate school for 2 years. Maximum pulmonary ventilation (VEmax) and maximal oxygen uptake (VO2max) for each subject were determined during maximal treadmill exercise. The slope (S) of ventilatory response to carbon dioxide at rest was measured by Read's rebreathing method. Mean values of VEmax increased statistically during training and decreased statistically during detraining. A similar tendency was observed in VO2max. The average value of S before training was 1.91 l.min-1.mmHg-1, (+/- ) SD 0.52 and it decreased gradually with increasing training periods; the difference between the S values before (1980) and after training (1982, 1983 and 1984) were all significant. Furthermore, the mean values of S increased significantly during detraining as compared with those obtained at the end of training (April 1984). We concluded that in normal subjects, long-term physical training increases aerobic work capacity and decreases CO2 ventilatory responsiveness, and that the ventilatory adaptations with training observed here are reversible through detraining.


[A clinical evaluation of uveitis-associated secondary glaucoma].
To investigate the clinical features of secondary glaucoma associated with uveitis. The subjects of the study were 1,604 eyes of 1,099 patients with uveitis at Miyata Eye Hospital, Miyakonojo, Miyazaki, between October 1974 and January 2000. The intraocular pressure (IOP) and clinical data were analyzed retrospectively. Secondary glaucoma was defined as being an IOP higher than 21 mmHg and needing treatment with medication to control the high IOP. Secondary glaucoma was found in 293 eyes (18.3%) of 217 patients (19.7%) among the uveitis patients. The clinical entity with the highest frequency of secondary glaucoma was Posner-Schlossman syndrome in 100%, followed by sarcoidosis in 34.1%, herpetic anterior uveitis in 30.4%, Behçet's disease in 20.8%, HLA-B 27 related acute anterior uveitis in 20.0%, Vogt-Koyanagi-Harada' disease in 16.4%, and HTLV-1 uveitis in 16.2%. Among the 293 eyes with secondary glaucoma, the majority (72%) had active anterior uveitis at the time of high IOP. Only 7.5% of secondary glaucoma eyes had peripheral anterior synechia wider than 180 degrees of trabecular meshwork. Steroid glaucoma was found only in 8.9% of the secondary glaucoma eyes. Surgical therapy mainly with trabeculectomy with anti-metabolites was performed in 38 eyes and the postsurgical IOP was controlled to 20 mmHg or lower in 36 eyes. Despite the medical and surgical therapy for secondary glaucoma, defect of the visual field was found in 38% of the secondary glaucoma eyes. The frequency of secondary glaucoma in 1,604 eyes with uveitis was 18.3%, and the frequency of secondary glaucoma differed depending upon the clinical entity of uveitis. The evaluation and the management of IOP are very important in treatment patients with uveitis, in addition to the management of intraocular inflammation.


Regulation of a dynamic interaction between two microtubule-binding proteins, EB1 and TIP150, by the mitotic p300/CBP-associated factor (PCAF) orchestrates kinetochore microtubule plasticity and chromosome stability during mitosis.
The microtubule cytoskeleton network orchestrates cellular dynamics and chromosome stability in mitosis. Although tubulin acetylation is essential for cellular plasticity, it has remained elusive how kinetochore microtubule plus-end dynamics are regulated by p300/CBP-associated factor (PCAF) acetylation in mitosis. Here, we demonstrate that the plus-end tracking protein, TIP150, regulates dynamic kinetochore-microtubule attachments by promoting the stability of spindle microtubule plus-ends. Suppression of TIP150 by siRNA results in metaphase alignment delays and perturbations in chromosome biorientation. TIP150 is a tetramer that binds an end-binding protein (EB1) dimer through the C-terminal domains, and overexpression of the C-terminal TIP150 or disruption of the TIP150-EB1 interface by a membrane-permeable peptide perturbs chromosome segregation. Acetylation of EB1-PCAF regulates the TIP150 interaction, and persistent acetylation perturbs EB1-TIP150 interaction and accurate metaphase alignment, resulting in spindle checkpoint activation. Suppression of the mitotic checkpoint serine/threonine protein kinase, BubR1, overrides mitotic arrest induced by impaired EB1-TIP150 interaction, but cells exhibit whole chromosome aneuploidy. Thus, the results identify a mechanism by which the TIP150-EB1 interaction governs kinetochore microtubule plus-end plasticity and establish that the temporal control of the TIP150-EB1 interaction by PCAF acetylation ensures chromosome stability in mitosis.


Source attributions of hazardous aromatic hydrocarbons in urban, suburban and rural areas in the Pearl River Delta (PRD) region.
Aromatic hydrocarbons (AHs) are both hazardous air pollutants and important precursors to ozone and secondary organic aerosols. Here we investigated 14 C6-C9 AHs at one urban, one suburban and two rural sites in the Pearl River Delta region during November-December 2009. The ratios of individual aromatics to acetylene were compared among these contrasting sites to indicate their difference in source contributions from solvent use and vehicle emissions. Ratios of toluene to benzene (T/B) in urban (1.8) and suburban (1.6) were near that of vehicle emissions. Higher T/B of 2.5 at the rural site downwind the industry zones reflected substantial contribution of solvent use while T/B of 0.8 at the upwind rural site reflected the impact of biomass burning. Source apportionment by positive matrix factorization (PMF) revealed that solvent use, vehicle exhaust and biomass burning altogether accounted for 89-94% of observed AHs. Vehicle exhaust was the major source for benzene with a share of 43-70% and biomass burning in particular contributed 30% to benzene in the upwind rural site; toluene, C8-aromatics and C9-aromatics, however, were mainly from solvent use, with contribution percentages of 47-59%, 52-59% and 41-64%, respectively.


Disparities between English and Spanish in readability of online endodontic information for laypeople.
In this study, the authors assessed the readability of online endodontic information in English and Spanish. The authors performed a systematic search in Google in May 2016. Search queries were "root canal treatment" and "¿Qué es una endodoncia?" without limits or filters. The authors assessed English readability by using Flesch-Kincaid Reading Grade Level, Flesch Reading Ease Score, Gunning Fog Index, Coleman-Liau index, automated readability index, and Simple Measure of Gobbledygook (SMOG) index. The authors calculated readability for Spanish by using the Fernández-Huerta index and INFLESZ (Ines-Barrio). The authors assessed the first 100 consecutive sites identified with each search strategy and selected 117 sites. Readability scores for English-language sites were in the category of normal to read, easily understood by 13- through 15-year-old students (Flesch Reading Ease Score, 63, interquartile range (IQR) [53.9-66.2]; Gunning Fog Index, 10.4, IQR [8.8-12]; Coleman-Liau index, 12.5, IQR [11.6-13.3]; and automated readability index, 8.6, IQR [6.7-9.8]). SMOG results led to the estimation that only 7 years of education would be needed to understand these contents (SMOG, 7.6, IQR [6.5-8.8]). Spanish-language sites had a readability index normal for an adult, equivalent to a seventh or eighth school year (Fernandez-Huerta, 62.3, IQR [59.7-66.6]; INFLESZ, 57.5, IQR [55.1-62.1]). The authors found that 36.6% of English-language sites had some degree of difficulty for readers to understand their contents, whereas 23% of Spanish-language sites had some degree of difficulty (14.46; 95% confidence interval, -3.16 to 30.08). Spanish- and English-language electronic health information about endodontic treatment is acceptable to read, but-particularly for English-language sites-there is an important proportion of sites scoring difficulty levels well above the recommendations. The internet is a useful tool for communicating with patients, but available endodontic information is difficult for laypeople to understand. Endodontists should produce relevant materials in plain language to overcome this problem.


The adaptation and validation of the satisfaction with stroke care questionnaire (Homesat) (SASC10-My™) for use in public primary healthcare facilities caring for long- term stroke survivors residing at home in the community.
Satisfaction with post stroke services would assist stakeholders in addressing gaps in service delivery. Tools used to evaluate satisfaction with stroke care services need to be validated to match healthcare services provided in each country. Studies on satisfaction with post discharge stroke care delivery in low- and middle-income countries (LMIC) are scarce, despite knowledge that post stroke care delivery is fragmented and poorly coordinated. This study aims to modify and validate the HomeSat subscale of the Dutch Satisfaction with Stroke Care-19 (SASC-19) questionnaire for use in Malaysia and in countries with similar public healthcare services in the region. The HomeSat subscale of the Dutch SASC-19 questionnaire (11 items) underwent back-to-back translation to produce a Malay language version. Content validation was done by Family Medicine Specialists involved in community post-stroke care. Community social support services in the original questionnaire were substituted with equivalent local services to ensure contextual relevance. Internal consistency reliability was determined using Cronbach alpha. Exploratory factor analysis was done to validate the factor structure of the Malay version of the questionnaire (SASC10-My™). The SASC10-My™ was then tested on 175 post-stroke patients who were recruited at ten public primary care healthcentres across Peninsular Malaysia, in a trial-within a trial study. One item from the original Dutch SASC19 (HomeSat) was dropped. Internal consistency for remaining 10 items was high (Cronbach alpha 0.830). Exploratory factor analysis showed the SASC10-My™ had 2 factors: discharge transition and social support services after discharge. The mean total score for SASC10-My™ was 10.74 (SD 7.33). Overall, only 18.2% were satisfied with outpatient stroke care services (SASC10-My™ score ≥ 20). Detailed analysis revealed only 10.9% of respondents were satisfied with discharge transition services, while only 40.9% were satisfied with support services after discharge. The SASC10-My™ questionnaire is a reliable and valid tool to measure caregiver or patient satisfaction with outpatient stroke care services in the Malaysian healthcare setting. Studies linking discharge protocol patterns and satisfaction with outpatient stroke care services should be conducted to improve care delivery and longer-term outcomes. No.: ACTRN12616001322426 (Registration Date: 21st September 2016.


Risks of paxlovid in a heart transplant recipient.
The burden of morbidity and mortality from SARS-CoV-2 infection is especially significant in heart transplant patients who are at higher risk for poor outcomes owing to immunosuppression, blunted response to vaccination, and multiple comorbid conditions. Over the last 3 years the therapeutic landscape for COVID-19 has evolved and our drug armamentaria continues to expand. With these advancements comes a time of great hope to mitigate significant illness from SARS - CoV - 2 infection. However, as with many emerging frontiers, the administration of novel therapeutics to a complex patient population remains challenging. We present a patient case encountered at our institution that highlights the need for increased awareness of nuances while managing COVID-19 infection in a heart transplant recipient.


Proteomic analysis of the membrane palmitoylated protein-4 (MPP4)-associated protein complex in the retina.
Membrane palmitoylated protein-4 (MPP4) is a retina-specific scaffolding protein of the membrane-associated guanylate kinase family that has been implicated in organizing presynaptic protein complexes in the photoreceptor ribbon synapse. To isolate the components of this complex we applied a proteomic approach based on immunoaffinity chromatography with a monoclonal anti-MPP4 antibody followed by two-dimensional electrophoresis and mass spectrometry. Among the identified molecules were previously reported proteins of the MPP4 scaffolding complex including adaptor proteins Veli3 and Psd95. Here we demonstrate a selective association between MPP4 and the Psd95-beta isoform that is mediated by interaction of their N-terminal L27 domains. In addition, we have identified recoverin and Hsc70 as novel associated proteins of the MPP4 multiprotein complex in the retina. This study demonstrates the utility of anti-MPP4 antibody precipitation for the elucidation of the MPP4-associated protein complex, which is essential in understanding its precise role in signal transmission at the photoreceptor synapse.


Ribosomal proteins in the fungus Podospora anserina: evidence for an electrophoretically altered 60S protein in a cycloheximide resistant mutant.
Proteins of cytoplasmic ribosomes of the Podospora anserina were analyzed by two dimensional gel electrophoresis. The numbers of proteins were estimated to be 28 in the small subunit and 41 in the large subunit. The L21 protein of the large subunit was found to migrate differently in a cycloheximide resistant mutant.


Inferior mesenteric venous sampling to detect colonic ischemia: a comparison with laser Doppler flowmetry and photoplethysmography.
No single method has been identified that accurately and reliably detects patients with impending bowel infarction during aortic reconstruction. Serial sampling of blood gas from the inferior mesenteric vein (IMV) for detecting colonic ischemia was compared with two previously described techniques: laser Doppler flowmetry (LDF) and photoplethysmography. Nine dogs underwent induced partial colonic ischemia followed by complete ischemia. Serial IMV blood gas measurements were obtained at four intervals: baseline, partial ischemia, complete ischemia, and reperfusion. Simultaneous direct colon wall LDF and PPG measurements also were obtained. Changes in pH, Po2, O2 saturation, and Pco2 demonstrated progressive acidosis, hypoxemia, and hypercapnia in association with progressive arterial occlusion and a reversal of these trends toward baseline after restoration of flow. The absence of a pulsatile photoplethysmography tracing and oxygen saturation less than 90% were predictive of altered perfusion but could not differentiate partial from complete ischemia. Although the differences in mean LDF values were statistically different during ischemia and reperfusion, there was considerable variability between each measurement. Analysis of blood gas from the IMV and pulse oximetry are useful techniques for detecting colonic ischemia, but only the former can distinguish partial from complete ischemia. The variability in colonic measurements with LDF limits its usefulness for detecting levels of colonic perfusion.


[About mnemonics of English translated TCM terms produced from morpheme-level translation].
The significance of morpheme-level translation in the standardization of English translation of TCM terms was discussed, and in order to seek out an effective way for remembering them, a further probe was given to the mnemonics of the new words produced from it.


Regulatory role of arachidonic acid-derived metabolites for proliferation of transformed murine Leydig cell in serum-free culture condition.
The growth-regulatory ability of eicosanoids from arachidonic acid is poorly understood. To investigate their role in cell growth, we cultured transformed murine Leydig cells (B-1 or B-1 F) in serum-free medium supplemented with various compounds modulating arachidonic acid metabolism. The addition of 5-lipoxygenase inhibitors (AA 861, NDGA and quercetin) showed a growth-stimulative effect. On the other hand, their growth was remarkably inhibited by arachidonic acid added into the culture medium. This growth-inhibiting ability of arachidonic acid was almost completely reversed by a simultaneous exposure of B-1 cells to lipoxygenase inhibitor. Exogenously added 5-HETE inhibited cell proliferation in a dose-dependent manner. These results suggest that 5-lipoxygenase-catalyzed products from arachidonic acid have the ability to suppress the proliferation of some transformed cells.


Severity of fatty liver on ultrasound correlates with metabolic and cardiovascular risk.
Non-alcoholic fatty liver disease is associated with an increased risk of metabolic and cardiovascular diseases. Whether the severity of fatty liver on ultrasound correlates with metabolic or cardiovascular risk remains unclear. A total of 1000 people receiving health examinations were enrolled, and 126 were excluded due to the presence of HBsAg, anti-HCV, known hepatic disorders or alcohol use (>140 g/wk). Significant fatty liver consisted of moderate and severe fatty liver on ultrasound. The definition of central obesity was modified to a waist circumference of >90 cm in men and >80 cm in women. Framingham risk score was used to estimate the risk of cardiovascular disease. A total of 874 subjects (485 women and 388 men with a mean age of 52.07 ± 11.68 years) were included in the final analysis. By using logistic regression analyses stratified by gender, the odds ratio for the prevalence of diabetes mellitus, metabolic syndrome and risk of cardiovascular disease increased with increasing fatty liver status in both genders (p ≤ 0.001). The difference was not only present between individuals with fatty liver vs. non-fatty liver but also between the mild fatty liver and significant fatty liver groups (p < 0.05). In conclusion, the severity of fatty liver on ultrasound could be useful for the risk stratification of metabolic syndrome, diabetes mellitus and cardiovascular disease in clinical practice.


Effect of thyroidectomy and thyroxine on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced immunotoxicity.
Radiothyroidectomy protected against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity in rats as assessed by the spleen anti-SRBC plaque-forming cell assay. Thyroxine (T4) replacement therapy partially reversed the effects of thyroidectomy on T4 and triiodothyronine (T3) serum levels, body weight and immune function as well as restored TCDD-induced immunotoxicity. Thus, hypothyroidism induced by TCDD exposure can be viewed as a protective response of the organism to reduce the insult caused by TCDD.


Long-term oncological and functional results of extraperitoneal laparoscopic radical prostatectomy: one surgical team's experience on 1,600 consecutive cases.
To determine the oncologic and functional outcomes of ELRP on a single surgical team's series. A total of 1,600 consecutive ELRP patients were recorded with a 2-year follow-up. In 778 patients, a 5-year follow-up was available. The mean operative time was 125,6 min (PLND not included) and 150,9 min (PLND included). Postoperative stage was pT2a in 282 patients (17.6 %), pT2b in 877 (54.8 %), pT2c in 18 (1.1 %), pT3a in 241 (15 %), and pT3b in 182 (11.3 %). Positive margins were detected in 7.4 and 13.4 % of pT2 and pT3 tumors, respectively. Overall complication rate was 4 %. PSA levels resulted in <0.2 ng/mL in 96.4, 94.9, 92, 90.9, and 81.5 % of the cases at 3, 12, 24, 36, and 60 months after surgery, respectively. BCRFS rates 5 years after ELRP were 88.7 % for patients staged as pT2, 73.9 % for pT3a, and 62.4 % for pT3b. Complete urinary continence rate resulted in 39 and 92 % after 1 and 12 months, respectively, with a further increase from 92 to 98.4 % at 24-month follow-up. A nerve-sparing procedure was performed in 45 % of patients. The overall potency rate at 12-month follow-up was 38.67 % for UNSS patients and 75 % for BNSS patients. Potency recovery was age-dependent, with patients aged <55 years who resulted potent in 46.8 % of UNSS and 95.8 % of BNSS after 24 months. ELRP is a standardized and safe procedure that implies advantages of both minimally invasive and extraperitoneal approaches with elevated standards for oncologic and functional outcomes obtained at long-term follow-up.


Game not over: Explaining older adults' use and intention to continue using a gamified eHealth service.
Gamification within eHealth services can increase eHealth adoption. However, little is known about factors affecting adoption of gamified eHealth among older adults. In this study, we sought to explain the (continued) use of a gamified eHealth service among older adults (55+). Participants used a gamified eHealth service, focusing on falls prevention, for 4 weeks and completed a post-test questionnaire based on the Technology Acceptance Model. We used Partial Least Squares Structural Equation Modeling to analyse our data. Seventy-two older adults participated with a mean age of 65.1 years (SD = 7.0). Our results show that first, perceived ease of use affected use of the service (use duration: β = 0.303, R2 = 0.130, and use frequency: β = 0.304, R2 = 0.107). Second, perceived usefulness affected the intention to continue using the service (β = 0.754, R2 = 0.640). Third, use of the service did not predict the intention to continue using it. Furthermore, enjoyment affected perceived usefulness (β = 0.783, R2 = 0.563) and aesthetics affected perceived ease of use (β = 0.634, R2 = 0.652). This study refutes the expected relation between use and intention to continue use a gamified eHealth service. Additionally, we learned that using theoretical approaches focusing on technology acceptance, are not suitable for explaining (continued) use of gamified eHealth services.


Exosome miR-3184-5p inhibits gastric cancer growth by targeting XBP1 to regulate the AKT, STAT3, and IRE1 signalling pathways.
MicroRNAs can regulate the transcription of protein-coding genes associated with the development and progression of cancer. In this study, we explored the potential diagnostic function of exosome miR-3184-5p in gastric cancer. This exosome was isolated from the blood samples of 150 patients with gastric cancer and 60 healthy participants. The mean particle size and concentration of serum exosome in the patients with gastric cancer were 104.6 nm (93.97-115.84) and 6.21e+009 particles/ml (5.15e+009-7.12e+009), respectively. miR-3184-5p expression was substantially downregulated in the patients with gastric cancer compared with that in the healthy participants. The gastric cancer cell line HGC-27 was cultured and transfected with the mimic and an inhibitor to overexpress and inhibit miR-3184-5p expression. miR-3184-5p strongly suppressed cell proliferation, migration, and invasion but induced cell apoptosis. Luciferase reporter assay revealed that XBP1 was the target of miR-3184-5p. miR-3184-5p substantially downregulated the expression of CD44, cyclin D1, MMP2, p65, p-AKT, and p-STAT3 but upregulated that of GRP78, IRE1, p-JNK, and CHOP. Moreover, miR-3184-5p cleaved caspase-12 and inhibited BCL-2 expression. These results suggested that the downregulation of miR-3184-5p in patients with gastric cancer might regulate the AKT, STAT3, and IRE1 pathways to promote the vitality of gastric cancer cells.


Transition and reversal: long-term experience of the MACE procedure in children.
Analysis of outcomes and follow-up of children who underwent the Malone antegrade continence enema (MACE) procedure in a UK tertiary paediatric surgery unit. Children who underwent a MACE procedure from 1998 to 2020 were identified. Demographic and clinical data were obtained from contemporaneous records. Outcomes were categorised as full (success), partial or failure. Ninety-five children were identified for inclusion (chronic idiopathic constipation (CIC, 59), anorectal malformations (ARM, 23) and Hirschsprung's disease (HD, 13)). Mean age at surgery was 9.4 years (3-19 years) and mean follow-up time was 6 years (0.3-16.8 years). Outcomes were successful in 69% of CIC patients, 78% in ARM and 69% in HD. Twenty (21%) underwent MACE reversal after developing independent continence, with a significant difference between groups (CIC 19%, ARM 9%, HD 54%, p = 0.0047). 50% of patients > 16 years old were transitioned to adult services. We report a success rate of 72% for MACE procedures in our unit, with a significant difference in reversal rate between diagnostic groups. Long term, a fifth of patients no longer required their MACE. When these patients reach adolescence, those who require ongoing support outside of the paediatric surgery setting should be safely transitioned to adult services.


Compound salvia pellet might be more effective and safer for chronic stable angina pectoris compared with nitrates: A systematic review and meta-analysis of randomized controlled trials.
Chronic stable angina (CSA) resulted in a considerable burden for both individuals and the society. In this study we aimed to critically evaluate the effectiveness and safety of Compound salvia pellet compared with nitrates in the treatment of Chronic Stable Angina (CSA) pectoris, and to provide more credible evidence for clinical practice. A comprehensive and exhaustive search strategy was formulated to identify potential RCTs of compound salvia pellet for CSA in international and Chinese databases from their inception to July 4th, 2018. We also searched the bibliographies of relevant studies. Two reviewers independently assessed the quality of included trials by using Cochrane Risk of Bias Tool. The literature search yielded 1849 citations and 51 RCTs (n = 4732) were included for meta-analysis after titles, abstracts and full text selection according to eligibility criteria. The pooled results suggested that compound salvia pellet was much more effective than nitrates in the improvement of angina symptoms (therapy = 4 weeks, RR = 1.23, 95%CI = [1.17, 1.30], P < .001, I = 0%; therapy = 4 weeks, RR = 1.13, 95%CI = [1.08, 1.17], P < .001, I = 45.6%), and ECG test (therapy = 4 weeks, RR = 1.24, 95%CI [1.14, 1.35], P < .001, I = 51.5%; and therapy > 4 weeks, RR = 1.30, 95%CI[1.20, 1.42], P < .001, I = 36.4%) in CSA. Compared with nitrates, the percentage of patients with adverse events significantly decreased when prescribed with compound salvia pellet (3.2% vs 17.0%). Compound salvia pellet might be more effective on the improvement of angina symptoms, ECG test and with few adverse events compared with nitrates. While there are some limitations in this study, which may weaken the results, we believe the findings could provide useful information for stakeholders concerned with outcomes in patients with CSA. More rigorous RCTs with high quality are needed to confirm these findings.


Local head gradient coils: window(s) of opportunity.
At the Medical College of Wisconsin (MCW), prior to the 1991 announcement of the discovery of BOLD fMRI, all of the technical pieces that were needed for efficient BOLD fMRI imaging were assembled for other applications, allowing MCW to jump into the fMRI business just days after the announcement. Central among these pieces was single shot EPI, implemented at MCW using a three axis local head gradient coil. This article describes the development of local gradient coil technology at MCW, and a historical perspective on local head gradient coils in general.


Current indications for spinal anesthesia-a narrative review.
Spinal anesthesia is a commonly performed regional anesthesia technique by most anesthesiologists worldwide. This technique is learned early during training and is relatively easy to master. Despite being an old technique, spinal anesthesia has evolved and developed in various aspects. This review attempts to highlight the current indications of this technique. Understanding the finer aspects and knowledge gaps will help postgraduates and practicing anesthesiologists in designing patient-specific techniques and interventions.


Phylogenetic inference rejects sporophyte based classification of the Funariaceae (Bryophyta): rapid radiation suggests rampant homoplasy in sporophyte evolution.
The moss family Funariaceae, which includes the model systems Funaria hygrometrica and Physcomitrella patens, comprises 15 genera, of which three accommodate approximately 95% of the 250-400 species. Generic concepts are drawn primarily from patterns in the diversity of morphological complexity of the sporophyte. Phylogenetic inferences from ten loci sampled across the three genomic compartments yield a hypothesis that is incompatible with the current circumscription of two of the speciose genera of the Funariaceae. The single clade, comprising exemplars of Funaria with a compound annulus, is congruent with the systematic concept proposed by Fife (1985). By contrast, Entosthodon and Physcomitrium are resolved as polyphyletic entities, and even the three species of Physcomitrella are confirmed to have diverged from distinct ancestors. Although the backbone relationships within the core clade of the Funariaceae remain unresolved, the polyphyly of these genera withstands alternative hypothesis testing. Consequently, the sporophytic characters that define these lineages are clearly homoplasious suggesting that selective pressures (or their relaxation) are in fact driving the diversification rather than the conservation of sporophytic architecture in the Funariaceae.


Usefulness of the severity and extent of reversible perfusion defects during thallium-dipyridamole imaging for cardiac risk assessment before noncardiac surgery.
Thallium-dipyridamole imaging is a very sensitive test for predicting cardiac events after noncardiac surgery, but it lacks specificity. To improve specificity, a semiquantitative scoring system was developed that combined dipyridamole-induced reversible left ventricular dilatation with scintigraphic indexes for severity and extent of reversible perfusion defects. Using this scoring system, patients were classified into low, intermediate and high risk subgroups. Thallium-dipyridamole imaging was performed in 66 patients before major general and vascular surgery. Thirty-nine patients classified as low risk (30 with normal scans and 9 with fixed defects) underwent surgery uneventfully. Surgery was cancelled in 6 patients with extensive thallium redistribution and coronary angiography was performed because of severe coronary artery disease in 5 and idiopathic dilated cardiomyopathy in 1. In the remaining 21 patients with thallium redistribution, a positive statistical correlation (p = 0.001) between scintigraphic indexes of severity and extent, and cardiac events was noted. Using cutoff values for the scintigraphic indexes, patients with reversible defects could be classified into intermediate and high risk subgroups. Only 1 of 11 patients at intermediate risk developed a complication, whereas 8 of 10 patients at high risk had a postoperative event (7 deaths and 1 myocardial infarction). Thus, using scintigraphic indexes for severity and extent, patients with reversible defects can be stratified into an intermediate risk subgroup that can safely undergo surgery and a high risk subgroup that requires coronary angiography.


Bleeding risk and mortality according to antithrombotic agents' exposure in cancer-related stroke patients: nationwide population-based cohort study in South Korea.
Ischemic stroke with active cancer is thought to have a unique mechanism compared to conventional stroke etiologies. There is no gold standard guideline for secondary prevention in patients with cancer-related stroke, hence, adequate type of antithrombotic agent for treatment is controversial. Subjects who were enrolled in National Health Insurance System Customized Research data during the period between 2010 and 2015 were observed until 2019. Subject diagnosed with ischemic stroke within six months before and 12 months after a cancer diagnosis was defined as cancer-related stroke patient. To solve immeasurable time bias, the drug exposure evaluation was divided into daily units, and each person-day was classified as four groups: antiplatelet, anticoagulant, both types, and unexposed to antithrombotic drugs. To investigate bleeding risk and mortality, Cox proportional hazards regression model with time-dependent covariates were used. Two thousand two hundred eighty-five subjects with cancer-related stroke were followed and analyzed. A group with anticoagulation showed high estimated hazard ratios (HRs) of all bleeding events compared to a group with antiplatelet (major bleeding HR, 1.35; 95% confidence interval [CI], 1.20-1.52; p < 0.001). And the result was also similar in the combination group (major bleeding HR, 1.54; 95% CI, 1.13-2.09; p = 0.006). The combination group also showed increased mortality HR compared to antiplatelet group (HR, 1.72; 95% CI, 1.47-2.00; p < 0.001). Bleeding risk increased in the anticoagulant-exposed group compared to antiplatelet-exposed group in cancer-related stroke patients. Thus, this result should be considered when selecting a secondary prevention drug.


Correction to: Are industry-funded charities promoting "advocacy-led studies" or "evidence-based science"?: a case study of the International Life Sciences Institute.
Since the publication of this article [1], the journal and the authors have received further context about the position of ILSI on the issue with the ILSI Mexico branch.


Clinical studies on carcinoembryonic antigen in pancreatic cancer.
We studied serum carcinoembryonic antigen (CEA) levels in 82 patients. Thirty-four of these had benign diseases while 48 had malignant diseases. Highest incidence and levels of CEA occurred in the sera of patients with pancreatic cancer and stomach cancer. In this paper we focused our particular attention on the serum CEA of 25 pancreatic cancer patients, and examined differences in serum CEA levels in relation to histologic differentiation and sites of pancreatric cancer. No statistical difference in serum CEA level was found among various histologic types and sites of the pancreatic cancer. Clinical courses of two patients with pancreatic cancer were also studied. Serial determinations of CEA levels are most useful in assessing the effect of operation or chemotherapies and are a useful indicator for differentiating pancreatic cancer from chronic pancreatitis but cannot be a conclusive factor for the diagnosis. Finally, we correlated serum CEA levels with those of RNase and confirmed a positive correlation.


A model for the development of human IgD-only B cells: Genotypic analyses suggest their generation in superantigen driven immune responses.
Human peripheral blood (PB) B cells expressing only IgD and tonsillar IgD-secreting plasma cells carry highly mutated V(H) genes and show preferential Iglambda usage. To further characterize these peculiar cells and gain insight into their generation, we analysed rearranged V(H) and V(L) genes of single IgD-only lambda(+) PB B cells and IgD(+) plasma cells from four individuals each. We demonstrate that the high somatic hypermutation activity in these cells is not restricted to V(H) genes but also present in V(L) genes. Moreover, not only PB IgD-only B cells, as reported earlier, but also IgD-expressing plasma cells often belong to very large clones. Surprisingly, the V(H)3-30 gene segment was used in each PB donor by >30% of IgD-only cells and in 2 tonsils by >50% of IgD plasma cells, whereas it was used less frequent in other B cells. All these features fit to a model in which IgD-only cells develop in superantigen-driven germinal center reactions, in which B cells are activated by binding of antigens to constant parts of Cdelta and often lambda light chains and the V(H)3-30 segment, and are selected for deletion of Cmu. IgD-only B cells may hence represent a unique B lineage subset generated in response to particular antigens.


Impact of multimodal therapy in locally recurrent rectal cancer.
The practice of salvaging recurrent rectal cancer has evolved. The aim of this study was to define the evolving salvage potential over time among patients with locally recurrent disease, and to identify durable determinants of long-term success. The study included consecutive patients with recurrent rectal cancer undergoing multimodal salvage with curative intent between 1988 and 2012. Predictors of long-term survival were defined by Cox regression analysis and compared over time. Re-recurrence and subsequent treatments were evaluated. After multidisciplinary evaluation of 229 patients, salvage therapy with curative intent included preoperative chemotherapy and/or radiotherapy (73·4 per cent; with 41·3 per cent undergoing repeat pelvic irradiation), surgical salvage resection with or without intraoperative irradiation (36·2 per cent), followed by postoperative adjuvant chemotherapy (38·0 per cent). Multivisceral resection was undertaken in 47·2 per cent and bone resection in 29·7 per cent. The R0 resection rate was 80·3 per cent. After a median follow-up of 56·5 months, the 5-year overall survival rate was 50 per cent in 2005-2012, markedly increased from 32 per cent in 1988-1996 (P = 0·044). Long-term success was associated with R0 resection (P = 0·017) and lack of secondary failure (P = 0·003). Some 125 patients (54·6 per cent) developed further recurrence at a median of 19·4 months after salvage surgery. Repeat operative rescue was feasible in 21 of 48 patients with local re-recurrence alone and in 17 of 77 with distant re-recurrence, with a median survival of 19·8 months after further recurrence. The long-term salvage potential for recurrent rectal cancer improved significantly over time, with the introduction of an individualized treatment algorithm of multimodal treatments and surgical salvage. Durable predictors of long-term success were R0 resection at salvage operation, avoidance of secondary failure, and feasibility of repeat rescue after re-recurrence.


Preliminary clinical evaluation of leuprorelin acetate depot injection in France, in the management of prostatic cancer.
In a preliminary multicentre clinical trial of 3.75 mg leuprorelin acetate depot 18 previously untreated patients with metastatic prostatic cancer were treated with the depot given subcutaneously once every 4 weeks for 28 weeks. Patients also received 100 mg nilutamide taken orally three times a day for the first 14 days of treatment to prevent flare-up. Leuprorelin acetate suppressed the serum testosterone concentration to castration levels; luteinizing hormone levels were also suppressed. The incidence of progressive disease was low and partial response occurred in five patients after treatment. No side-effects were assigned to the flare-up period. It is concluded that leuprorelin acetate depot is a safe and efficacious treatment for metastatic prostatic cancer.


DNA electrophoresis in agarose gels: a simple relation describing the length dependence of mobility.
Electrophoretic mobilities of DNA molecules ranging in length from 100 to 10 000 base pairs (bp) were measured in gels of eleven concentrations of agarose from 0.5 to 1.5%. Excellent fits of the dependence of mobility on DNA length were obtained with the relationship [equation: see text] showing an e(-L/gamma) crossover, where L is the length of a DNA fragment and gamma is a crossover length ranging from 8000 to 12000 bp. The other parameters in the fit are mu(s) the mobility of short DNA with unit charge in the limit as length is extrapolated to zero, and muI, the mobility of long DNA as length is extrapolated to infinity. This exponential relationship should be a useful interpolation function for determining DNA lengths over a wide range. The simplicity of this relationship may be of more fundamental significance and suggests that some common feature dominates the electrophoresis of double stranded DNA fragments in agarose gels, regardless of length.


Absorption kinetics of subcutaneously injected insulin. Evidence for degradation at the injection site.
The absorption of subcutaneously injected insulin was examined by injecting semisynthetic [3H] insulin in anaesthetized pigs and subsequently analysing the tissue excised from the injection site. Contrary to previously accepted views, a significant proportion of insulin was degraded at the injection site. The disappearance of intact [3H] insulin from the injection site followed a monoexponential function with a half-time of 59 min.


A synthetic acceptor substrate for Trypanosoma brucei UDP-Gal: GPI anchor side-chain alpha-galactosyltransferases.
A synthetic analogue of a trisaccharide fragment of the Trypanosoma brucei Variant Surface Glycoprotein (VSG) GlycosylPhosphatidyInositiol (GPI) anchor, Gal-alpha-1,3(Man-alpha-1,6)-Man-alpha-O-octyl (1), serves as a substrate for two T. brucei alpha-galactosyltransferases. The principle tetrasaccharide product derived from (1) contains a Gal-alpha-1,2-Gal linkage.


Development and validation of a duplex RT-qPCR assay for norovirus quantification in wastewater samples.
Norovirus (NoV) is a highly contagious enteric virus that causes widespread outbreaks and a substantial number of deaths across communities. As clinical surveillance is often insufficient, wastewater-based epidemiology (WBE) may provide novel pathways of tracking outbreaks. To utilise WBE, it is important to use accurate and sensitive methods for viral quantification. In this study, we developed a one-step duplex RT-qPCR assay to simultaneously test the two main human pathogenic NoV genogroups, GI and GII, in wastewater samples. The assay had low limits of detection (LOD), namely 0.52 genome copies (gc)/µl for NoVGI and 1.37 gc/µl for NoVGII. No significant concentration-dependent interactions were noted for both NoVGI and for NoVGII when the two targets were mixed at different concentrations in the samples. When tested on wastewater-derived RNA eluents, no significant difference between duplex and singleplex concentrations were found for either target. Low levels of inhibition (up to 32 %) were noted due to organic matter present in the wastewater extracts. From these results we argue that the duplex RT-qPCR assay developed enables the sensitive detection of both NoVGI and NoVGII in wastewater-derived RNA eluents, in a time and cost-effective way and may be used for surveillance to monitor public and environmental health.


The protein tyrosine phosphatase inhibitor, pervanadate, is a powerful antidiabetic agent in streptozotocin-treated diabetic rats.
The effect of pervanadate, a potent insulinomimetic agent that inhibits insulin receptor dephosphorylation in vitro, is now assessed in vivo. A single i.p. administration of pervanadate at concentrations as low as 700 micrograms vanadium/kg body wt markedly lowered blood glucose levels in streptozotocin-induced diabetic rats from 430 +/- 28 to 212 +/- 30 mg/100 ml within 3 h. A decrease was already observed half hour after treatment, continued in accelerating fashion to the 3rd h, and persisted for at least 24 h. The initial hyperglycemia reoccurred on the second day and remained thereafter. In comparable fashion, pervanadate decreased the blood glucose levels of control healthy rats, treated identically. Within this period body wt was not significantly altered in either group. This data indicate that rapid and efficient management of glucose homeostasis is achieved via inhibiting receptor dephosphorylation. This observation may lead to a new therapeutic approach of protein tyrosine phosphatase inhibition for future treatment of diabetes in general, and in insulin resistant states in particular.


Grapevine VlbZIP30 improves drought resistance by directly activating VvNAC17 and promoting lignin biosynthesis through the regulation of three peroxidase genes.
Drought stress severely affects grapevine quality and yield, and recent reports have revealed that lignin plays an important role in protection from drought stress. Since little is known about lignin-mediated drought resistance in grapevine, we investigated its significance. Herein, we show that VlbZIP30 mediates drought resistance by activating the expression of lignin biosynthetic genes and increasing lignin deposition. Transgenic grapevine plants overexpressing VlbZIP30 exhibited lignin deposition (mainly G and S monomers) in the stem secondary xylem under control conditions, which resulted from the upregulated expression of VvPRX4 and VvPRX72. Overexpression of VlbZIP30 improves drought tolerance, characterized by a reduction in the water loss rate, maintenance of an effective photosynthesis rate, and increased lignin content (mainly G monomer) in leaves under drought conditions. Electrophoretic mobility shift assay, luciferase reporter assays, and chromatin immunoprecipitation-qPCR assays indicated that VlbZIP30 directly binds to the G-box cis-element in the promoters of lignin biosynthetic (VvPRX N1) and drought-responsive (VvNAC17) genes to regulate their expression. In summary, we report a novel VlbZIP30-mediated mechanism linking lignification and drought tolerance in grapevine. The results of this study may be of value for the development of molecular breeding strategies to produce drought-resistant fruit crops.


Crystallized dextran nanospheres with entrapped antigen and their use as adjuvants.
A novel and simple method is described of preparing a matrix with entrapped antigen, the matrix consisting of well characterized carbohydrates with low toxicity, i.e., dextran and starch, stabilized by crystallization. The crystallized carbohydrate spheres produced probably derive their adjuvant effect from slow antigen release and macrophage stimulation. Five months after a single injection of 80 micrograms ovalbumin entrapped in dextran spheres, mice produced antibodies against ovalbumin and this response could be enhanced further by co-entrapment of immunomodulators such as DEAE- or SO4-dextrans into the spheres. A single injection of 8 micrograms entrapped bee venom into mice gave the same IgG antibody response as 2 X 80 micrograms bee venom dissolved in water. By the same method it was possible to inject 4 times the LD50 dose of entrapped bee venom in mice without any significant side reactions.


Renewed interest in preejectional isovolumic phase: new applications of tissue Doppler indexes: implications to ventricular dyssynchrony.
There is renewed interest in isovolumic contraction (IC) in tissue Doppler echocardiography of the myocardial walls, which is revisited in this editorial with new regional velocity data. The aims are to recall traditional background information and to emphasize the need to master the rapidly evolving tissue Doppler procedures for the accurate display of brief IC. IC, a preejectional component of great physiologic interest, is very demanding in terms of ultrasound technology. The onset and end of its motion velocities should be unambiguously defined versus the QRS complex and ejection wall motion. This is a prerequisite for exploiting the new information as guidance toward new therapeutic strategies from a practical viewpoint. However, IC preload dependence should be kept in mind, because of its limited potential for contractility studies. Finally, when only duration measurements are made in the assessment of ventricular dyssynchrony, regional preejectional duration is the pertinent tool to single out the onset of ejection local wall motion.


Effect of botulinum toxin treatment on quality of life in patients with isolated lingual dystonia and oromandibular dystonia affecting the tongue.
The purpose of this study was to investigate the impact of botulinum toxin (BoNT) treatment on the quality of life (QoL) for patients with prominent lingual dystonia (LD) using a disease-specific questionnaire, the oromandibular dystonia questionnaire-25 (OMDQ-25). This is a prospective, observational study of a cohort of 30 patients treated with BoNT injections for LD, with or without concurrent jaw dystonia. Primary efficacy outcome was the absolute difference between total OMDQ-25 baseline score and total OMDQ-25 scores 4 and 8 weeks after the treatment. Safety outcome was the occurrence of adverse effects. The mean total OMDQ-25 baseline score was 46.8 ± 17.8. After BoNT treatment, there was a significant reduction in the mean total OMDQ-25 score at 4 weeks (38.2 ± 17.6; p = 0.004), as well as at 8 weeks (39.6 ± 18.1; p = 0.008). At the multiple regression analysis, a jaw deviation pattern (JDD) and high questionnaire baseline total score were detected as predictors of a better outcome, whilst associated jaw tremor was a predictor of poor outcome. In patients with JDD, jaw-opening muscles were more frequently injected and genioglossus less frequently than in patients without JDD. No major adverse events were detected. A consistent and measurable improvement in QoL, with good safety and tolerability, can be achieved in patients with prominent LD by injecting BoNT into genioglossus and/or other muscles of the oromandibular region.


Linear phase-error correction for improved water and fat separation in dual-echo dixon techniques.
Large and spatially-linear phase errors along the frequency-encode direction may be induced by several common and hard-to-avoid system imperfections such as eddy currents. For data acquired in dual-echo Dixon techniques, the linear phase error can be more aggravated when compared to that acquired in a single echo and can pose challenges to a phase-correction algorithm necessary for successful Dixon processing. In this work, we propose a two-step process that first corrects the linear component of the phase errors with a modified Ahn-Cho algorithm (Ahn CB and Cho ZH, IEEE Trans. Med. Imaging 6:32, 1987) and then corrects the residual phase errors with a previously-developed region-growing algorithm (Ma J, Magn. Res. Med. 52:415, 2004). We demonstrate that successive application of the two-step process to data from a dual-echo Dixon technique provides a "1-2 punch" to the overall phase errors and can overcome local water and fat separation failures that are observed when the region-growing-based algorithm is applied alone.


Multidrug-resistant gram-negative bacteria among patients who require chronic hemodialysis.
Multidrug-resistant gram-negative bacteria are rapidly spreading throughout the world. The epidemiology of multidrug-resistant gram-negative bacteria in patients who require chronic hemodialysis has not been previously studied. A prospective cohort study of an outpatient hemodialysis unit was conducted. Serial surveillance cultures for multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus were collected from patients who were undergoing chronic hemodialysis. Nineteen (28%) of the 67 enrolled patients were colonized with one or more antimicrobial-resistant bacteria at study enrollment. Eleven (16%), nine (13%), and three (5%) patients were colonized with multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, respectively. Independent risk factors associated with harboring multidrug-resistant gram-negative bacteria at enrollment were residence in a long-term care facility and antibiotic exposure for > or = 7 d in the previous 3 mo. Twenty-two (40%) of 55 patients who had follow-up cultures acquired at least one antimicrobial-resistant bacterium. A total of 20, 15, and 13% of patients acquired multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, respectively. Antibiotic exposure was the only independent risk factor for multidrug-resistant gram-negative bacteria acquisition. Endogenous multidrug-resistant gram-negative bacteria acquisition was detected among 69% of acquired multidrug-resistant gram-negative bacterial strains. The prevalence and acquisition of multidrug-resistant gram-negative bacteria surpassed that of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. Endogenous acquisition, as opposed to patient-to-patient spread, was the predominant mechanism of acquisition. Residence in a long-term care facility and antibiotic exposure may be important factors promoting the spread of multidrug-resistant gram-negative bacteria among this patient population.


Heat-stroke: a review of rapid cooling techniques.
Patients with prolonged hyperpyrexia due to heat-stroke have a poor outcome. Thus, the most important feature in the management of heat-stroke is rapid cooling. There are several methods of cooling available, such as fan therapy, cold water immersion, iced baths and evaporative cooling. Based on military and civilian experiences worldwide the development of protocols based on evaporative cooling is advocated as the most efficient.