FIR and IIR Synapses, a New Neural Network Architecture for Time Series Modeling.
A new neural network architecture involving either local feedforward global feedforward, and/or local recurrent global feedforward structure is proposed. A learning rule minimizing a mean square error criterion is derived. The performance of this algorithm (local recurrent global feedforward architecture) is compared with a local-feedforward global-feedforward architecture. It is shown that the local-recurrent global-feedforward model performs better than the local-feedforward global-feedforward model.


Up-regulation of long non-coding RNA PCAT-1 correlates with tumor progression and poor prognosis in gastric cancer.
Long non-coding RNAs (lncRNAs), emerging non-coding RNAs, have been proved to serve as a critical role in the proliferation, metastasis apoptosis of gastric cancer. However, the potential biological role PCAT-1 in gastric cancer (GC) remains undefined. The present study aimed to investigate the expression and clinical significance of PCAT-1 in GC. The expression of PCAT-1 was detected with a quantitative Real-time PCR assay. The association between PCAT-1 expression and clinicopathological factors, as well as survival rates, was analyzed. Cox proportional-hazards regression analysis was applied in order to estimate univariate and multivariate hazard ratios for overall survival. Then, effects of PCAT-1 on the biological behavior of GC cells were investigated. We found that PCAT-1 expression was elevated in GC tissues and cell lines, and PCAT-1 levels were highly positively correlated with invasion depth (p < 0.001), TNM stages (p < 0.001) and lymphatic metastasis (p = 0.003). The biological function of PCAT-1 was explored and the results showed silencing of PCAT-1 could suppress cell proliferation, migration and invasion in vitro. Kaplan-Meier analysis demonstrated that increased PCAT-1 expression contributed to poor overall survival (OS) (p < 0.01). Furthermore, in a multivariate Cox model, our results showed that PCAT-1 expression was an independent poor prognostic factor for OS in GC. Our finding suggested that PCAT-1 may have potential roles as a biomarker and/or a therapeutic target in gastric cancer.


Sonochemical design of cerium-rich anticorrosion nanonetwork on metal surface.
As a "green chemistry" tool, ultrasound irradiation of high intensity was successfully applied to formation of cerium/aluminum oxide anticorrosion protective layers on metal surfaces. The mechanism of metal surface modification in the presence of cerium(III) aqueous solution results from two components: activation of the metal surface by localized heating and activation of cerium ions which are diffused within liquid jets at high velocity to the metal surface. The ultrasonically increased reactivity of cerium and the developed surface of the metal stimulate formation of a novel type of cerium-enriched protective layer: cerium/aluminum oxide nanonetwork, where cerium oxide and aluminum oxide are interlaced in a mixed layer strongly connected to the metal surface. A combination of microscopic and spectroscopic methods was applied to study structure and morphology of the coatings as well as to optimize the ultrasound-assisted preparation method. The anticorrosion activity of the novel cerium/aluminum oxide system was demonstrated by using the scanning vibrating electrode technique.


Studies on resistance to breathing.
Some aspects of resistance to breathing are reviewed in this article. The importance in medicine of the determination of resistance to breathing is emphasized. Estimation of respiratory resistance in clinical practice by spirometry is mentioned. Clinically useful methods for determination of resistance to breathing reported in the literature are reviewed. The body plethysmograph, an instrument specially designed to measure airway resistance and currently used in clinical medicine, is complicated and expensive. A newly designed instrument for measuring total respiratory resistance by partial airway occlusion is strongly recommended. A comparison of the two methods, body plethysmography and partial airway occlusion, has been made. The theory of the partial airway occlusion method is also briefly described. Factors affecting respiratory resistance are analyzed. The relationship between the size of dead space and the magnitude of respiratory resistance is also discussed.


Chronic Disseminated Salmonellosis in a Patient With Interleukin-12p40 Deficiency.
Interleukin (IL)-12 is composed of p35 and p40 subunits; in this case, IL-12p40 deficiency is a rare genetic etiology of Mendelian susceptibility to mycobacterial disease. Salmonellosis has been reported in almost half of these patients and mostly present in recurrent extraintestinal form. In this report, we described an 18-month-old boy with absence of IL-12p40 production suffering from chronic disseminated nontyphoidal salmonellosis. To the best of our knowledge, this is the first-reported case.


Ethical and methodological issues in academic mental health research in populations affected by disasters: the Oklahoma City experience relevant to September 11, 2001.
Empirical data from research studies are vital to guiding mental health interventions following disasters. However, few data are available for this purpose. Important advances in policy and procedures for the conduct of organized research emerged from the Oklahoma City bombing, yielding cooperative working relationships among researchers and culminating in the ethical attainment of informative research data. However, the academic community was again caught off guard after the September 11, 2001, terrorist attacks. Suggestions to surmount these obstacles include incorporating research infrastructures into disaster preparedness plans in advance; organizing the community of researchers; and working closely with major funding organizations. Methodological issues pertaining to measurement of psychopathology include the importance of obtaining diagnostic data; interpreting the meaning of symptoms in the absence of a psychiatric disorder; differentiating preexisting symptoms from those that emerged after the disaster, and optimal timing of postdisaster assessment.


Effect of the Home to Hospital to Home nutrition management program on postoperative liver cancer patients: A single-center randomized controlled study.
Malnutrition is the most common complication in postoperative liver cancer patients. This study aimed to investigate the effects of the Home to Hospital to Home nutrition management program on postoperative liver cancer patients. A total of 184 liver cancer patients were randomly assigned to either an intervention group (treated under the Home to Hospital to Home nutrition management program) or a control group (treated with the general nutritional method). Nutrition-related indicators, such as prealbumin (PA) and albumin, were assessed before and after treatment in both groups. The incidence of complications (e.g., nausea or vomiting, bloating, difficulty defecating, ascites), length of hospital stay, first time to anal exhaust and out-of-bed activity, and patient satisfaction were recorded. A total of 184 liver cancer patients were randomly assigned to either an intervention group (treated under the Home to Hospital to Home nutrition management program) or a control group (treated with the general nutritional method). Nutrition-related indicators, such as prealbumin (PA) and albumin, were assessed before and after treatment in both groups. The incidence of complications (e.g., nausea or vomiting, bloating, difficulty defecating, ascites), length of hospital stay, first time to anal exhaust and out-of-bed activity, and patient satisfaction were recorded. The Home to Hospital to Home nutrition management program improves the nutritional status of postoperative liver cancer patients, lowers the incidence of complications, shortens hospital stays, increases patient satisfaction, and promotes the early recovery of patients.


Fetal chlorpyrifos exposure: adverse effects on brain cell development and cholinergic biomarkers emerge postnatally and continue into adolescence and adulthood.
Fetal and childhood exposures to widely used organophosphate pesticides, especially chlorpyrifos (CPF), have raised concerns about developmental neurotoxicity. Previously, biomarkers for brain cell number, cell packing density, and cell size indicated that neonatal rats were more sensitive to CPF than were fetal rats, yet animals exposed prenatally still developed behavioral deficits in adolescence and adulthood. In the present study, we administered CPF to pregnant rats on gestational days 17-20, using regimens devoid of overt fetal toxicity. We then examined subsequent development of acetylcholine systems in forebrain regions involved in cognitive function and compared the effects with those on general biomarkers of cell development. Choline acetyltransferase, a constitutive marker for cholinergic nerve terminals, showed only minor CPF-induced changes during the period of rapid synaptogenesis. In contrast, hemicholinium-3 binding to the presynaptic choline transporter, which is responsive to nerve impulse activity, displayed marked suppression in the animals exposed to CPF; despite a return to nearly normal values by weaning, deficits were again apparent in adolescence and adulthood. There was no compensatory up-regulation of cholinergic receptors, as m2-muscarinic cholinergic receptor binding was unchanged. CPF also elicited delayed-onset alterations in biomarkers for general aspects of cell integrity, with reductions in cell packing density, increases in relative cell size, and contraction of neuritic extensions; however, neither the magnitude nor timing of these changes was predictive of the cholinergic defects. The present findings indicate a wide window of vulnerability of cholinergic systems to CPF, extending from prenatal through postnatal periods, occurring independently of adverse effects on general cellular neurotoxicity.


Weighted unequal error protection for transmitting scalable object-oriented images over packet-erasure networks.
In this paper, we investigate the problem of transmitting embedded encoded object-oriented images over the packet-erasure networks. After giving a review of the existing combined unequal error protection (CUEP) and individual unequal error protection (IUEP) schemes, a novel weighted unequal error protection (WUEP) packetization scheme is proposed, which serves as an alternative to the existing methods. In our proposed framework, the embedded bitstreams of all concerned image objects are packetized into multiple description packet streams before transmission. Two levels of rate allocation are introduced: intraobject rate allocation provides unequal error protection to the embedded bitstream of each object and minimizes its associated mean distortion; interobject rate allocation aims at minimizing the weighted mean distortion by adaptively allocating the rate budget among different objects according to their importance. Furthermore, our proposed packetization scheme ensures independent access and manipulation of individual image object. A detailed comparison between CUEP, IUEP, and WUEP is presented along with the experimental results, so that one can choose the most suitable approach according to the requirements.


SGAM: an array-based approach for high-resolution genetic mapping in Saccharomyces cerevisiae.
The development of genome-scale resources and high-throughput methodologies has enabled systematic assessment of gene function in vivo. Synthetic genetic array (SGA) analysis automates yeast genetic manipulation, permitting diverse analysis of approximately 5,000 viable deletion mutants in Saccharomyces cerevisiae. SGA methodology has enabled genome-wide synthetic lethal screening and construction of a large-scale genetic interaction network for yeast. Genetic networks often reveal new components of specific pathways and functional relationships between genes whose products buffer one another or impinge on a common essential pathway. Because SGA analysis can be used to manipulate any genetic element linked to a selectable marker, it is a highly versatile approach that can be adapted for a variety of different genetic screens, including synthetic lethality, dosage suppression, and dosage lethality. This chapter focuses on a specific SGA application for high-resolution genetic mapping, referred to as SGA mapping (SGAM), which enables the identification of suppressor mutations and thus provides a powerful means for interrogating gene function and pathway order.


The impact of referring patients with drug-resistant focal epilepsy to an epilepsy center for presurgical diagnosis.
Epilepsy surgery is an established treatment for drug-resistant focal epilepsy (DRFE) that results in seizure freedom in about 60% of patients. Correctly identifying an epileptogenic lesion in magnetic resonance imaging (MRI) is challenging but highly relevant since it improves the likelihood of being referred for presurgical diagnosis. The epileptogenic lesion's etiology directly relates to the surgical intervention's indication and outcome. Therefore, it is vital to correctly identify epileptogenic lesions and their etiology presurgically. We compared the final histopathological diagnoses of all patients with DRFE undergoing epilepsy surgery at our center between 2015 and 2021 with their MRI diagnoses before and after presurgical diagnosis at our epilepsy center, including MRI evaluations by expert epilepsy neuroradiologists. Additionally, we analyzed the outcome of different subgroups. This study included 132 patients. The discordance between histopathology and MRI diagnoses significantly decreased from 61.3% for non-expert MRI evaluations (NEMRIs) to 22.1% for epilepsy center MRI evaluations (ECMRIs; p < 0.0001). The MRI-sensitivity improved significantly from 68.6% for NEMRIs to 97.7% for ECMRIs (p < 0.0001). Identifying focal cortical dysplasia (FCD) and amygdala dysplasia was the most challenging for both subgroups. 65.5% of patients with negative NEMRI were seizure-free 12 months postoperatively, no patient with negative ECMRI achieved seizure-freedom. The mean duration of epilepsy until surgical intervention was 13.6 years in patients with an initial negative NEMRI and 9.5 years in patients with a recognized lesion in NEMRI. This study provides evidence that for patients with DRFE-especially those with initial negative findings in a non-expert MRI-an early consultation at an epilepsy center, including an ECMRI, is important for identifying candidates for epilepsy surgery. NEMRI-negative findings preoperatively do not preclude seizure freedom postoperatively. Therefore, patients with DRFE that remain MRI-negative after initial NEMRI should be referred to an epilepsy center for presurgical evaluation. Nonreferral based on NEMRI negativity may harm such patients and delay surgical intervention. However, ECMRI-negative patients have a reduced chance of becoming seizure-free after epilepsy surgery. Further improvements in MRI technique and evaluation are needed and should be directed towards improving sensitivity for FCDs and amygdala dysplasias.


Feasibility of Nonanonymous Burnout Surveys in a Large Academic Department.
Burnout is prevalent among clinicians and entails negative personal, professional, and organizational consequences. Assessments of burnout are typically anonymous to facilitate psychological safety. This limits the capacity of leadership to help struggling providers and reduces the level of demographic detail. Nonanonymous, confidential assessments may facilitate outreach to individuals or targeted interventions for at-risk populations. We administered the Maslach Burnout Inventory to physician faculty and advanced practice providers in an academic department of family medicine. We identified a wellness officer within the department who served as an honest broker to keep nonanonymous survey responses confidential. Respondents had the option of taking the survey anonymously or confidentially. Anonymous respondents were allowed to withhold demographic information to ensure anonymity. Sixty-seven of 109 providers responded (61% response rate), with 46 (69%) doing so confidentially. Burnout rates were similar between groups: 48% among confidential respondents, and 43% among anonymous respondents (P=.71). Subscales of the MBI also showed no significant differences. Because a large proportion of anonymous respondents withheld demographic data, no demographic trends could be identified among them. Younger confidential respondents were more likely to exhibit depersonalization (P=.01). Most participants chose to respond confidentially. There was no significant difference in the level of burnout between confidential and anonymous respondents. Our findings refute the conventional wisdom that clinicians require anonymity to respond to burnout surveys. This finding has the potential to open a new line of inquiry regarding burnout, its drivers and potential solutions.


H2O2-triggered "off/on signal" nanoparticles target P-selectin for the non-invasive and contrast-enhanced theranostics for arterial thrombosis.
Pathological coagulation within an injured artery and the subsequent cardiovascular complications, such as stroke and heart attack, greatly threaten human life. Inspired by the biochemical features of acute arterial thrombosis, such as abundant activated platelets and hydrogen peroxide (H2O2), we constructed platelet-targeted theranostic nanoparticles (CyBA/PFM NPs) with H2O2-triggered photoacoustic contrast enhancement and antithrombotic capabilities. CyBA/PFM NPs were designed to target platelet-rich clots via fucoidan segment within the carrier, which could be activated by H2O2 to produce fluorescent "CyOH" molecules, thus turning on the photoacoustic signal. CyBA/PFM NPs showed obvious amplification of fluorescence following incubation with fresh clots, exhibiting efficient scavenging ability of intracellular reactive oxygen species (ROS). In a FeCl3-induced mouse model of carotid thrombosis, CyBA/PFM NPs significantly amplified the photoacoustic contrast in thrombogenic tissues, effectively eliminated ROS within the occlusion site, and suppressed the thrombus formation, accompanied by a normalization of the soluble CD40L level. Given their accurate imaging potential, potent antithrombotic activities and acceptable biosafety, CyBA/PFM NPs hold strong potential as nanoscale theranostics for H2O2-correlated cardiovascular diseases. STATEMENT OF SIGNIFICANCE: In this study, we developed a platelet-targeted and H2O2-triggered nanosystem self-assembled from phenylboronated fucoidan/maltodextrin polymers and responsive near-infrared probes. The fucoidan segment within the carrier could facilitate the specific delivery of the therapeutic polymers and probes to the platelet-rich arterial thrombus. In a mouse model of FeCl3-induced arterial thrombosis, the system could be activated by H2O2 to produce fluorescent "CyOH" molecules, thus turning on the photoacoustic signal and specifically imaging thrombosed tissues. Besides, CyBA/PFM NPs significantly effectively eliminated ROS within the occlusion site and suppressed the thrombus formation. Given their theranostic potential and acceptable biosafety, this system has great potential for H2O2-correlated cardiovascular diseases.


Demystifying critical care management. Part 1.
Many nurse executives avoid an active management role in their hospital's critical care areas, a stance that can result in decreased personal, professional, and institutional efficiency and effectiveness. This article is a guide for applying the management process in critical care units and for helping nurse executives gain control of one of the largest consumers of hospital and nursing resources. This is part 1 of a two-part article.


Inflammation, atherosclerotic burden and cardiovascular prognosis.
The aim of this study was to evaluate the impact of various inflammatory markers on atherosclerotic burden and cardiovascular prognosis. In a prospective study 720 patients preceding coronary angiography were enrolled. In all patients carotid and leg arteries were examined using sonographic methods and C-reactive protein, fibrinogen, interleukin-18 (IL-18) and interleukin-6 have been determined. Patients were compared with regard to atherosclerotic burden: no clinically significant stenosis (N=57, 7.9%), coronary artery disease only (N=362, 50.3%), coronary artery disease with peripheral atherosclerosis (=multi-vascular atherosclerosis, N=301, 41.8%). Follow-up data after a median of 6.5 years were available in 719 patients (99.9%), 75 patients (10.4%) died from cardiovascular causes. Presence of multi-vascular atherosclerosis, elevation of IL-18 and elevation of fibrinogen were independently related to cardiovascular death in a fully adjusted model Hazard ratio (95% confidence interval) 2.0 (1.2-3.5) for presence of multi-vascular atherosclerosis (P<0.01), 2.2 (1.2-3.9) for high fibrinogen (P<0.01) and 2.8 (1.6-4.9) for high IL-18 (P<0.0001)). Fibrinogen was achieved as independent predictor for both, mortality and atherosclerotic burden, whereas IL-18 was not related to atherosclerotic burden. IL-18 was an independent predictor for future cardiovascular death but was not associated with extent of atherosclerosis, whereas fibrinogen was independently related to cardiovascular death and extent of disease.


[Smoking: knowledge, attitudes, habits and degree of dependence of young adults in Salvador].
This study was aimed at evaluating the degree of smoking dependence and to characterize social demographic data, habits and attitudes of young smokers. Answered the questionnairel02 students from Salvador, State of Bahia, of which 11 were smokers. Their mean age and the age in which they first smoked were 18.2 and 13.4 years respectively. Most of them were male, in the first year of senior high school, of brown skin color and had close relatives who smoke. The majority of those young smokers had been advised about the risks of smoking at home and in school, but few had knowledge about the benefits of quitting. Almost half of them had been smoking for more than three years and had started to smoke out of curiosity. More than half of them smoked one cigarette per day, with low levels of nicotine, bought the cigarettes in shops, and wanted and tried to quit smoking, but never succeeded. The degree of dependence was low for most of them. This study offers hints for nurses to act against smoking with young adults.


The World Hypertension League: where now and where to in salt reduction.
High dietary salt is a leading risk for death and disability largely by causing increased blood pressure. Other associated health risks include gastric and renal cell cancers, osteoporosis, renal stones, and increased disease activity in multiple sclerosis, headache, increased body fat and Meniere's disease. The World Hypertension League (WHL) has prioritized advocacy for salt reduction. WHL resources and actions include a non-governmental organization policy statement, dietary salt fact sheet, development of standardized nomenclature, call for quality research, collaboration in a weekly salt science update, development of a process to set recommended dietary salt research standards and regular literature reviews, development of adoptable power point slide sets to support WHL positions and resources, and critic of weak research studies on dietary salt. The WHL plans to continue to work with multiple governmental and non-governmental organizations to promote dietary salt reduction towards the World Health Organization (WHO) recommendations.


Bibliometric and authorship trends over a 30 year publication history in two representative US sports medicine journals.
Bibliometric studies are important to understand changes and improvement opportunities in academia. This study compared bibliometric trends for two major sports medicine/arthroscopy journals, the American Journal of Sports Medicine® (AJSM®) and Arthroscopy® over the past 30 years. Trends over time and comparisons between both journals were noted for common bibliometric variables (number of authors, references, pages, citations, and corresponding author position) as well as author gender and continental origin. Appropriate statistical analyses were performed. A p < 0.001 was considered statistically significant. One representative year per decade was used. There were 814 manuscripts from AJSM® and 650 from Arthroscopy®. For AJSM® the number of manuscripts steadily increased from 86 in 1986 to 350 in 2016; for Arthroscopy® the number of manuscripts increased from 73 in 1985/1986, to 267 in 2006, but then dropped to 229 in 2016. There were significant increases in all bibliometric variables, except for the number of citations which decreased in Arthroscopy®. There were significant differences in manuscript region of origin by journal (p = 0.000002). Arthroscopy® had a greater percentage of manuscripts from Asia than AJSM® (19.3% vs 11.5%) while AJSM® had a greater percentage from North America (70.3% vs 59.2%); both journals had similar percentages from Europe (18.2% for AJSM® and 21.6% for Arthroscopy®). For AJSM® the average percentage of female first authors was 13.3%, increasing from 4.7% in 1986 to 19.3% in 2016; the average percentage of female corresponding authors was 7.3%. For Arthroscopy®, the average percentage of female first authors was 8.1%, increasing from 2.8% in 1985/1986 to 15.7% in 2016 (p = 0.00007). In conclusion, AJSM® and Arthroscopy® showed an increase in most variables analyzed. Although Arthroscopy® is climbing at a higher rate than AJSM® for female authors, AJSM® has an overall greater percentage of female authors.


The neurotrophin receptor, gp75, forms a complex with the receptor tyrosine kinase TrkA.
The high-affinity NGF receptor is thought to be a complex of two receptors , gp75 and the tyrosine kinase TrkA, but direct biochemical evidence for such an association had been lacking. In this report, we demonstrate the existence of such a gp75-TrkA complex by a copatching technique. Gp75 on the surface of intact cells is patched with an anti-gp75 antibody and fluorescent secondary antibody, the cells are then fixed to prevent further antibody-induced redistributions, and the distribution of TrkA is probed with and anti-TrkA antibody and fluorescent secondary antibody. We utilize a baculovirus-insect cell expression of wild-type and mutated NGF receptors. TrkA and gp75 copatch in both the absence and presence of NGF. The association is specific, since gp75 does not copatch with other tyrosine kinase receptors, including TrkB, platelet-derived growth factor receptor-beta, and Torso (Tor). To determine which domains of TrkA are required for copatching, we used a series of TrkA-Tor chimeric receptors and show that the extracellular domain of TrkA is sufficient for copatching with gp75. A chimeric receptor with TrkA transmembrane and intracellular domains show partial copatching with gp75. Deletion of the intracellular domain of gp75 decreases but does not eliminate copatching. A point mutation which inactivates the TrkA kinase has no effect on copatching, indicating that this enzymatic activity is not required for association with gp75. Hence, although interactions between the gp75 and TrkA extracellular domains are sufficient for complex formation, interactions involving other receptor domains also play a role.


Interaction of hormone-sensitive lipase with steroidogenic acute regulatory protein: facilitation of cholesterol transfer in adrenal.
Hormone-sensitive lipase (HSL) is responsible for the neutral cholesteryl ester hydrolase activity in steroidogenic tissues. Through its action, HSL is involved in regulating intracellular cholesterol metabolism and making unesterified cholesterol available for steroid hormone production. Steroidogenic acute regulatory protein (StAR) facilitates the movement of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane and is a critical regulatory step in steroidogenesis. In the current studies we demonstrate a direct interaction of HSL with StAR using in vitro glutathione S-transferase pull-down experiments. The 37-kDa StAR is coimmunoprecipitated with HSL from adrenals of animals treated with ACTH. Deletional mutations show that HSL interacts with the N-terminal as well as a central region of StAR. Coexpression of HSL and StAR in Chinese hamster ovary cells results in higher cholesteryl ester hydrolytic activity of HSL. Transient overexpression of HSL in Y1 adrenocortical cells increases mitochondrial cholesterol content under conditions in which StAR is induced. It is proposed that the interaction of HSL with StAR in cytosol increases the hydrolytic activity of HSL and that together HSL and StAR facilitate cholesterol movement from lipid droplets to mitochondria for steroidogenesis.


A biomechanical comparison of successful and unsuccessful power clean attempts.
Although the power clean is an almost ubiquitous exercise in the strength and conditioning setting, relatively little is known about the biomechanics of successful and unsuccessful power clean lift attempts. The purpose of this study was to determine biomechanical differences between successful and unsuccessful power clean lift attempts in male collegiate athletes. Fifteen male lacrosse players (Age: 20.1 ± 1.2; Height: 1.78 ± 0.07 m; Body mass: 80.4 ± 8.1 kg; Relative one-repetition maximum power clean: 1.25 ± 0.13 kg/kg) were videotaped during a lifting session that required the completion of maximal effort power cleans to establish a one-repetition maximum. The position of the barbell was digitised and used to calculate the displacement, velocity, acceleration, and acceleration vector of the barbell. The results revealed that unsuccessful attempts were characterised by differences during the second pull phase. Unsuccessful lifts exhibited greater peak forward barbell displacement, lower backward barbell velocities, and lower resultant acceleration angles during the second pull. Strength and conditioning coaches should therefore emphasise limited forward motion of the barbell during the second pull and instruct athletes to generate a more backward-directed force during the second pull in order to lift greater loads during testing and subsequent lifting sessions.


Understanding a role for hypoxia in lesion formation and location in the deep and periventricular white matter in small vessel disease and multiple sclerosis.
The deep and periventricular white matter is preferentially affected in several neurological disorders, including cerebral small vessel disease (SVD) and multiple sclerosis (MS), suggesting that common pathogenic mechanisms may be involved in this injury. Here we consider the potential pathogenic role of tissue hypoxia in lesion development, arising partly from the vascular anatomy of the affected white matter. Specifically, these regions are supplied by a sparse vasculature fed by long, narrow end arteries/arterioles that are vulnerable to oxygen desaturation if perfusion is reduced (as in SVD, MS and diabetes) or if the surrounding tissue is hypoxic (as in MS, at least). The oxygen crisis is exacerbated by a local preponderance of veins, as these can become highly desaturated 'sinks' for oxygen that deplete it from surrounding tissues. Additional haemodynamic deficiencies, including sluggish flow and impaired vasomotor reactivity and vessel compliance, further exacerbate oxygen insufficiency. The cells most vulnerable to hypoxic damage, including oligodendrocytes, die first, resulting in demyelination. Indeed, in preclinical models, demyelination is prevented if adequate oxygenation is maintained by raising inspired oxygen concentrations. In agreement with this interpretation, there is a predilection of lesions for the anterior and occipital horns of the lateral ventricles, namely regions located at arterial watersheds, or border zones, known to be especially susceptible to hypoperfusion and hypoxia. Finally, mitochondrial dysfunction due to genetic causes, as occurs in leucodystrophies or due to free radical damage, as occurs in MS, will compound any energy insufficiency resulting from hypoxia. Viewing lesion formation from the standpoint of tissue oxygenation not only reveals that lesion distribution is partly predictable, but may also inform new therapeutic strategies.


The effect of surface treatment of the interfacial surface on fatigue-related microtensile bond strength of milled zirconia to veneering porcelain.
The success of zirconia-reinforced all-ceramic crowns depends on the formation of a stable bond between the zirconia core and the veneering porcelain. The purpose of this study was to test the effects of liner application and airborne particle abrasion of a postsintered Y-TZP core on the bond strength between the zirconia core and veneering porcelain with or without cyclic loading. Kavo Everest® Y-TZP blank disks were sintered and divided into three treatment groups: airborne particle abrasion, IPS e.max® Ceram Zirliner application, or no surface treatment. The disks were then veneered with IPS e.max® ZirPress veneering porcelain. Half the veneered disks from each group were cyclically loaded. This created six experimental groups: three surface treatment groups cyclically loaded and three not loaded. The disks were then sectioned into microbars for microtensile bond strength (MTBS) testing (40 specimens per group). Specimens were luted to a fixture mount and loaded to failure using a universal testing machine (MTS Insight). The maximum force was measured and bond strength computed. Data were analyzed with a two-way ANOVA and Tukey's HSD test (α= 0.05). Airborne particle abrasion significantly decreased MTBS values (p= 0.043), and ZirLiner application did not have a significant effect on MTBS values compared to control. Cyclic loading did not have a significant effect on MTBS values. The predominant failure mode in all groups was mixed. Airborne particle abrasion of the interfacial surface of the Everest® Y-TZP core significantly decreased the MTBS to ZirPress veneering porcelain when compared to no interfacial surface treatment. Application of ZirLiner to the interfacial surface of the Everest® Y-TZP core did not significantly increase or decrease the MTBS to ZirPress veneering porcelain, compared to the other surface treatments. Cyclic loading did not affect bond strengths in any of the groups, regardless of surface treatment. Neither cyclic loading nor surface treatment affected the failure mode of the specimens.


Natural-source d-α-tocopheryl acetate inhibits oxidant stress and modulates atopic asthma in humans in vivo.
Asthma is associated with oxidant stress and diminished antioxidant defenses. Yet, the mechanistic role of oxidant stress and antioxidant supplementation in human asthmatics remains uncertain. We determined the effect of high doses of the antioxidant natural-source d-α-tocopheryl acetate for 16 weeks on allergen-induced airway oxidant stress, inflammation, and bronchial responsiveness to methacholine and allergen in atopic asthmatics in vivo. Thirty-three mild atopic asthmatics underwent bronchoscopy with baseline bronchoalveolar lavage and segmental allergen challenge. The allergen-challenged airway was lavaged 24 h later. At least 3 weeks later, patients underwent inhaled challenges with methacholine and specific allergen. Volunteers took 1500 IU of natural-source d-α-tocopheryl acetate daily for at least 16 weeks. At the end of the treatment, the two bronchoscopies and inhaled methacholine and allergen challenges were repeated. F(2)-isoprostanes, specific markers of oxidant stress, and selected Th1 and Th2 cytokines were analyzed in the lavage fluid. Following supplementation of natural-source d-α-tocopheryl acetate, plasma concentrations of α-tocopherol increased and γ-tocopherol decreased. Both baseline and allergen-induced F(2)-isoprostanes significantly decreased, providing biochemical evidence for an antioxidant effect. Natural-source d-α-tocopheryl acetate reduced allergen-provoked concentrations of interleukin 3 and interleukin 4 and augmented levels of interleukin 12 in bronchoalveolar lavage fluid. Natural-source d-α-tocopheryl acetate improved airway responsiveness to methacholine but did not alter airway reactivity to specific allergen. Inhibition of oxidant stress by natural-source d-α-tocopheryl acetate modulates allergic inflammation and airway hyperresponsiveness in human atopic asthmatics in vivo. These results need to be confirmed by a randomized placebo-controlled trial.


ANTI-REFLUX PROCEDURES AFTER ROUX-EN-Y GASTRIC BYPASS.
Roux-en-Y gastric bypass (RYGB) has been the choice of bariatric procedure for patients with symptomatic reflux - and is known to be effective in reducing the need for anti-reflux medication postoperatively. However, a small number of RYGB patients can still develop severe reflux symptoms that require a surgical intervention. To examine and describe the patient population that requires an anti-reflux procedure after RYGB evaluating demographics, characteristics, symptoms and diagnosis. A retrospective chart review was performed on 32 patients who underwent a hiatal hernia repair and/or Nissen fundoplication after RYGB Jul 1st, 2014 and Dec 31st, 2019. Patients were identified using the MBSAQIP database and their electronic medical records were reviewed. Most patients were female (n=29, 90.6%). The mean age was 52.8 years and the mean body mass index (BMI) was 34.1 kg/m2 at the time of anti-reflux procedure. Patients underwent the anti-reflux procedure at a mean of 7.9 years after the RYGB procedure. The mean percentage of excess BMI loss during the time between RYGB and anti-reflux procedure was 63.4%. Female patients with a significant weight loss may develop a severe reflux symptoms years after RYGB. Complaints of reflux after RYGB should not be overlooked. Careful follow-up and appropriate treatment (including surgical intervention) is needed for this population.


Ventral surgical approaches to craniovertebral junction chordomas.
Chordomas are primarily malignant tumors encountered at either end of the neural axis; the craniovertebral junction and the sacrococcygeal junction. In this article, we discuss the surgical management of craniovertebral junction chordomas. In this paper, we discuss the surgical management of craniovertebral junction chordomas. The following approaches are illustrated: transoral-transpalatopharyngeal approach, high anterior cervical retropharyngeal approach, endoscopic transoral approach, and endoscopic transnasal approach. No single operative approach can be used for all craniovertebral chordomas. Therefore, the location of the tumor dictates which approach or approaches should be used.


[Clinical observation on electroacupuncture for arousing consciousness of comatose patients with severe trauma brain injury].
To observe the arousal effect of electroacupuncture (EA) stimulation of Baihui (GV 20), Shuigou (GV 26), etc. on severe craniocerebral injury patients. A total of 90 cases of severe craniocerebral injury were randomly allocated to routine medication, naloxone and EA groups, with 30 cases in each group. For patients of the routine medication group, mild hypothermia therapy, medicines for dehydration, hormonal therapy, vascular dilation, cerebral nutrition supporting, anti-inflammation, etc. were given. For patients of the naloxone group, intravenous drip of naloxone 0.4 mg/kg in the first 3 days, 0.2 mg/kg for 7 days and 0. 1 mg/kg afterwards. For patients of the EA group, EA (1 Hz/50 Hz) was given for 30 min once daily. All the treatments were conducted once a day for 14 days. The Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) were used for assessing the therapeutic effect. In comparison with pre-treatment in each one of the routine medication, naloxone and EA groups, GCS scores were all obviously increased in the 3 groups following the treatment, and one month's follow-up (P<0. 05). The GCS scores of both naloxone and EA groups were significantly higher than those of the routine medication group (P<0.05). No significant difference was found between the naloxone group and EA group in GCS scores (P>0. 05). According to the GOS, one month's follow-up showed that of the three 30 cases in the routine medication, naloxone and EA groups, 6, 12 and 14 were improved, 8, 10 and 10 moderate handicap, 8, 3 and 2 severe handicap, 5, 3 and 2 vegetative state, and 3, 2 and 2 dead, with the arousal rates being 46. 66% , 73. 33% and 80. 00%, respectively. The therapeutic effects of both naloxone and EA groups were significantly superior to those of the routine medication group (P<0.05). EA intervention at early stage can promote the recovery of neurological function, accelerate the consciousness from coma and improve the outcomes of patients with severe traumatic brain injury.


Improving HbA1c with Glucose Self-Monitoring in Diabetic Patients with EpxDiabetes, a Phone Call and Text Message-Based Telemedicine Platform: A Randomized Controlled Trial.
Background:We conducted a randomized controlled trial of EpxDiabetes, a novel digital health intervention as an adjunct therapy to reduce HbA1c and fasting blood glucose (FBG) among patients with type 2 diabetes mellitus (T2DM). In addition, we examined the effect of social determinants of health on our system.Methods:Sixty-five (n = 65) patients were randomized at a primary care clinic. Self-reported FBG data were collected by EpxDiabetes automated phone calls or text messages. Only intervention group responses were shared with providers, facilitating follow-up and bidirectional communication. ΔHbA1c and ΔFBG were analyzed after 6 months.Results:There was an absolute HbA1c reduction of 0.69% in the intervention group (95% confidence interval [CI], -1.41 to 0.02) and an absolute reduction of 0.03% in the control group (95% CI, -0.88 to 0.82). For those with baseline HbA1c >8%, HbA1c decreased significantly by 1.17% in the intervention group (95% CI, -1.90 to -0.44), and decreased by 0.02% in the control group (95% CI, -0.99 to 0.94). FBG decreased in the intervention group by 21.6 mg/dL (95% CI, -37.56 to -5.639), and increased 13.0 mg/dL in the control group (95% CI, -47.67 to 73.69). Engagement (proportion responding to ≥25% of texts or calls over 4 weeks) was 58% for the intervention group (95% CI, 0.373-0.627) and 48% for the control group (95% CI, 0.296-0.621). Smoking, number of comorbidities, and response rate were significant predictors of ΔHbA1c.Conclusions:EpxDiabetes helps to reduce HbA1c in patients with uncontrolled T2DM and fosters patient-provider communication; it has definite merit as an adjunct therapy in diabetes management. Future work will focus on improving the acceptability of the system and implementation on a larger scale trial.


Cell-surface proteins of Streptococcus sanguis associated with cell hydrophobicity and coaggregation properties.
Incubating cells of Streptococcus sanguis with sodium lauroyl sarcosinate, under conditions that did not cause lysis, solubilized material comprising 5-8% of the cell dry weight. The treatment reduced cell hydrophobicity, and reduced the ability of the cells to coaggregate with Actinomyces spp. The extract contained about 20 polypeptides and these were identified as being cell-surface components on the basis of one or more of the following criteria: being degraded when cells were incubated with protease; being labelled when cells were iodinated using a lactoperoxidase-catalysed reaction; reacting with antibodies raised to fixed whole cells. Eight of the polypeptides accounted for more than 70% of the total protein extracted, and one component (molecular mass 16 kDa) was hydrophobic. The cell-surface proteins described are implicated in cell hydrophobicity and coaggregation.


[Physiological tooth migration in hydroxyapatite grafts with bony regeneration. Animal study].
Tooth migration into jaw segments where granular hydroxy apatite had been implanted was studied in rats. To prevent premature contact with the ceramic granules, tooth germs were completely removed in the animals at the age of 10 days. Tooth root contact with the ceramo-osseous complex as a result of physiological tooth migration had deleterious effects. In the light of these findings the implantation of granular hydroxy apatite in the vicinity of tooth roots is not advisable.


Single-Bubble Sonoluminescence of Colloidal Suspensions of Europium(II) Salt Nanoparticles.
Colloidal suspensions of EuCl2, EuBr2, and EuSO4 nanoparticles (<50 nm) in dodecane and EuSO4 in 70% H2SO4 were synthesized. Moving single-bubble sonoluminescence (m-SBSL) spectra were obtained for a bubble performing radial oscillations in these suspensions and translational motions at the antinode of a standing ultrasonic wave with a frequency of about 27 kHz. In these spectra (at a spectral resolution of 10 nm), the sono-excited luminescence bands of the Eu2+ ion were detected for the first time, coinciding in the shape and position of the maxima (404, 413, and 377 nm for EuCl2, EuBr2, and EuSO4, respectively) with the bands of Eu2+ located in a crystalline environment in the photoluminescence spectra of nanoparticles of europium salts in suspensions. The detected sonoluminescence of Eu2+ arises due to the injection of nanoparticles into a bubble deformed during motion and excitation of a lanthanide ion at the periphery of the bubble volume during collisions of nanoparticles with charged particles, mainly electrons, coming from a hot nonequilibrium plasma, which periodically arises during bubble compression. Evidence for the excitation of the europium ion in the bubble is the absence of its luminescence bands in the SBSL spectra of the translationally immobile bubble, in which nanoparticles are unlikely to enter. The nanoparticles that enter the bubble also undergo decomposition in the plasma into fragments, in particular, with the formation of Eu, Eu+ in the excited state. The atomic lines of these fragments were recorded for the first time in the m-SBSL spectrum with a resolution of 1 nm for a suspension of EuSO4 nanoparticles in 70% H2SO4. The resulting m-SBSL spectra will add to the library of characteristic spectra of objects of sonoluminescent spectroscopic analysis and will make it possible to identify and determine the content of Eu or Eu2+ in these objects.


The Correlation Between Electrodiagnostic Results and Ultrasonographic Findings in the Severity of Carpal Tunnel Syndrome in Females.
To determine which ultrasonographic measurement can be used as an indicator reflecting the severity of carpal tunnel syndrome (CTS), by comparing electrodiagnostic results with ultrasonographic measurements in females. Many previous studies have tried to reveal that the ultrasonography (US) can possibility be used for diagnosis and severity of CTS. However, the criteria are different by gender. Thus far, there have been many efforts towards providing patients with a CTS diagnosis and severity prediction using US, but studies' results are still unclear due to lack of data on gender differences. We collected data from 54 female patients. We classified the severity of CTS according to electrodiagnostic results. Ultrasonographic measurements included proximal and distal cross-sectional areas of the median nerve and carpal tunnel. The severity by electrodiagnostic results statistically correlated to the proximal cross-sectional area (CSA) of the median nerve and carpal tunnel. However, there was no relationship between the proximal and distal nerve/tunnel indexes and the severity by electrodiagnostic results. In female patients with CTS, the proximal CSAs of the median nerve and carpal tunnel increase. They correlate with the severity by electrodiagnostic findings. The CSA of the proximal median nerve could be particularly used as a predictor of the severity of CTS in female patients. However, the nerve/tunnel index is constant, irrespective of the severity of CTS.


Transmission dynamics of extended-spectrum β-lactamase and AmpC β-lactamase-producing Escherichia coli in a broiler flock without antibiotic use.
Extended-spectrum and AmpC β-lactamase-producing Escherichia coli (ESBL/AmpC-EC) are found throughout the broiler production pyramid. Transmission of resistance between broilers and humans could occur at any point, representing a potential public health issue. Insight in farm transmission dynamics could provide a basis for control, leading to fewer contaminated broilers. The aim was quantifying transmission rates and routes of ESBL/AmpC-EC, and specific phylogenetic groups, in an organic broiler flock without antibiotic use. In each of two consecutive production rounds, 80 randomly chosen broilers were followed individually. Cloacal swabs from these, 20 other randomly chosen broilers, and 11 environmental samples were taken at several moments from arrival till slaughter. ESBL/AmpC-EC were isolated by selective pre-enrichment, and ESBL/AmpC-genes and E. coli phylogenetic groups were determined. Transmission parameters (β) were estimated using a Generalised Linear Model with a susceptible-infectious-susceptible model. Effect of direct broiler contact as compared to contact through the environment and previous carriage c.q. infectious status and their interaction were included as explanatory variables. Multiplying β by the length of the infectious period gives the reproduction ratio (R). On day 1, prevalence was 28.8% (95%CI 19.2-40.0%) and 0.0% (95%CI 0.0-4.5%) among individually followed broilers, in round 1 and 2 respectively. In round 2, the environment was positive before arrival of day-old chicks. After 3 days, almost 100% of broilers and environmental samples were positive in both rounds. Most samples were positive for CTX-M-1 group genes, and A1 and B1 were predominant phylogenetic groups. From day 3 there was a shift towards more phylogenetic groups. R was 1.70 (95%CI 0.55-5.25) for total ESBL/AmpC-EC. Risk for broilers to become infectious was lower if previously infectious (βpreviously infectious=0.02 vs. βnot previously infectious=3.41; P<0.0001). For phylogenetic groups separately, R was 0.88 (95%CI 0.38-2.07), 0.51 (95%CI 0.27-0.98), 0.99 (95%CI 0.65-1.51) for A1, B1 and rest (i.e. A0, B2, D1, D2) groups, respectively. The interaction effect for A1 and B1 was reflected in the fact that when broilers were previous infectious, the environment was relatively more important for transmission of the A1 group, while this was direct contact between broilers for the B1 group. Positive day-old chicks and the environment both play a role in introduction and transmission of ESBL/AmpC-EC in flocks. These results suggest that, even without selective pressure from antibiotics, total ESBL/AmpC-EC persistence, and resulting endemic situation, seem to be caused by shifts in carriage of different phylogenetic groups. It implies that contaminated broilers enter the slaughterhouse.


Robotic and neuronal simulation of the hippocampus and rat navigation.
The properties of hippocampal place cells are reviewed, with particular attention to the nature of the internal and external signals that support their firing. A neuronal simulation of the firing of place cells in open-field environments of varying shape is presented. This simulation is coupled with an existing model of how place-cell firing can be used to drive navigation, and is tested by implementation as a miniature mobile robot. The sensors on the robot provide visual, odometric and short-range proximity data, which are combined to estimate the distance of the walls of the enclosure from the robot and the robot's current heading direction. These inputs drive the hippocampal simulation, in which the robot's location is represented as the firing of place cells. If a goal location is encountered, learning occurs in connections from the concurrently active place cells to a set of 'goal cells', which guide subsequent navigation, allowing the robot to return to an unmarked location. The system shows good agreement with actual place-cell firing, and makes predictions regarding the firing of cells in the subiculum, the effect of blocking long-term synaptic changes, and the locus of search of rats after deformation of their environment.


Patients' attitudes to discontinuing not-indicated long-term antidepressant use: barriers and facilitators.
Long-term antidepressant use has increased exponentially, though this is not always according to guidelines. Our previous randomized controlled trial (RCT) showed that participants using antidepressants long term without a proper indication were apprehensive to stop: only half were willing to attempt to discontinue their antidepressant use. The objective of this study was to explore participants' barriers and facilitators for stopping long-term antidepressant use without a current proper indication. Semistructured interviews with participants from the intervention group of our RCT, a cluster-RCT in general practice in the Netherlands. The latter study was a stop trial with patients on long-term antidepressant use without a current indication (no psychiatric diagnosis). Participants of the intervention group of the RCT had been provided with advice to stop antidepressants. Participants of the current interview study were purposively sampled (from the intervention group of the RCT) to ensure diversity in age, sex, and intention to discontinue the antidepressant. Analysis was performed as an iterative process, based on the constant comparative method. Data collection proceeded until saturation was reached. A total of 16 participants were interviewed. Fear (of recurrence, relapse, or to disturb the equilibrium) was the most important barrier; prior attempts fueled these anticipations. Also prominent as a barrier was the notion that antidepressants are necessary to counter a deficiency of serotonin. Facilitators were information on duration of usage given at the time of first prescription and confidence in a successful attempt. We found many participants struggling between barriers and facilitators to discontinue and participants not discontinuing while experiencing no barriers (ambivalence). Fear is an important motive for patients considering discontinuation of antidepressants. Serotonin deficiency as explanation for antidepressant effectiveness promotes life-long use and hinders discontinuation of antidepressant treatment. The prospect of discontinuation at first prescription can facilitate a future discontinuation attempt. General practitioners should be aware of their patients' fears, expectations, and attributions toward antidepressant use/discontinuation, and of new developments in taper methods.


Monitoring plant phenology using digital repeat photography.
Repeated observations of plant phenology have been shown to be important indicators of global change. However, capturing the exact date of key events requires daily observations during the growing season, making phenologic observations relatively labor intensive and costly to collect. One alternative to daily observations for capturing the dates of key phenologic events is repeat photography. In this study, we explored the utility of repeat digital photography for monitoring phenologic events in plants. We provide an illustration of this approach and its utility by placing observations made using repeat digital imagery in context with local meteorologic and edaphic variables. We found that repeat photography provides a reliable, consistent measurement of phenophase. In addition, digital photography offers advantages in that it can be mathematically manipulated to detect and enhance patterns; it can classify objects; and digital photographs can be archived for future analysis. In this study, an estimate of greenness and counts of individual flowers were extracted by way of mathematic algorithms from the photo time series. These metrics were interpreted using meteorologic measurements collected at the study site. We conclude that repeat photography, coupled with site-specific meteorologic measurements, could greatly enhance our understanding environmental triggers of phenologic events. In addition, the methods described could easily be adopted by citizen scientists and the general public as well as professionals in the field.


SLC30A3 (ZnT3) oligomerization by dityrosine bonds regulates its subcellular localization and metal transport capacity.
Non-covalent and covalent homo-oligomerization of membrane proteins regulates their subcellular localization and function. Here, we described a novel oligomerization mechanism affecting solute carrier family 30 member 3/zinc transporter 3 (SLC30A3/ZnT3). Oligomerization was mediated by intermolecular covalent dityrosine bonds. Using mutagenized ZnT3 expressed in PC12 cells, we identified two critical tyrosine residues necessary for dityrosine-mediated ZnT3 oligomerization. ZnT3 carrying the Y372F mutation prevented ZnT3 oligomerization, decreased ZnT3 targeting to synaptic-like microvesicles (SLMVs), and decreased resistance to zinc toxicity. Strikingly, ZnT3 harboring the Y357F mutation behaved as a "gain-of-function" mutant as it displayed increased ZnT3 oligomerization, targeting to SLMVs, and increased resistance to zinc toxicity. Single and double tyrosine ZnT3 mutants indicate that the predominant dimeric species is formed between tyrosine 357 and 372. ZnT3 tyrosine dimerization was detected under normal conditions and it was enhanced by oxidative stress. Covalent species were also detected in other SLC30A zinc transporters localized in different subcellular compartments. These results indicate that covalent tyrosine dimerization of a SLC30A family member modulates its subcellular localization and zinc transport capacity. We propose that dityrosine-dependent membrane protein oligomerization may regulate the function of diverse membrane protein in normal and disease states.


At Least Three Transporters Likely Mediate Threonine Uptake Needed for Mouse Embryonic Stem Cell Proliferation.
Stem cells are at the forefront of current regenerative and biomedical research. Thus, there exists an imperative and urgent need to understand the mechanisms that drive stem cell function in order to exploit their use as a therapeutic tool. Amino acids are potent inducers of signaling cascades that drive stem cell proliferation and differentiation. With a focus on mouse embryonic stem (mES) cells, Threonine (Thr) is the only amino acid required in culture media for mES cell proliferation. Current research associates this need for Thr with threonine dehydrogenase (TDH), which catabolizes Thr to glycine and acetyl-CoA in mES cells. This theory depends, in part, on the ability of 3- hydroxynorvaline (3-HNV) to inhibit both TDH and mES cell proliferation. However, the concentration of 3-HNV needed to inhibit mES cell proliferation is more than an order of magnitude less than its apparent Ki for TDH inhibition. Additionally, 3-HNV inhibits human embryonic stem (hES) cell proliferation, but hES cells do not express a functional tdh gene. Such findings indicate another mechanism for Thr stimulated mES and hES cell proliferation. Since amino acid transporters may be inducers of signaling cascades, we characterized the Thr transport systems in mES cells. We found that there is a Na(+)-dependent and a Na(+)-independent component of substrate-saturable transport, with the Na(+)-dependent component predominating. We also found that of 20 amino acids tested, the amino acids that were the strongest inhibitors of the Na(+)-dependent component of radiolabeled Thr transport were Ser, Cys, 4-OH-Pro, Asn, Met, and non-radiolabeled Thr itself. Such findings are consistent with characteristics of the ASC transport system, suggesting that this ASC system is responsible for the majority of Thr transport in mES cells. We confirmed expression of mRNA encoding the ASC system transporters, ASCT1 and ASCT2, in mES cells using RT-PCR. In conclusion, mES cells likely express at least three transporters of Thr; at least two Na(+)-dependent transporters and one Na(+)-independent one.


Analytical Performance Evaluation of a 523-Gene Circulating Tumor DNA Assay for Next-Generation Sequencing-Based Comprehensive Tumor Profiling in Liquid Biopsy Samples.
Next-generation sequencing (NGS)-based comprehensive tumor profiling from liquid biopsy samples can significantly improve diagnosis and monitoring of tumors when high-quality tissue material is difficult to obtain. In addition, it offers the potential to capture the entire complexity of the tumor, which is particularly important for highly heterogeneous or metastatic tumors. Here, we report the findings of an analytical performance evaluation of the TruSight Oncology 500 circulating tumor DNA (ctDNA) assay, a 523-gene NGS panel developed for ctDNA-based comprehensive genomic profiling of tumors, using reference and patient samples. Using 30 ng cell-free DNA, the assay showed high sensitivity and low variant detection variability for single-nucleotide variants, insertions and deletions, and fusions down to a variant allele frequency (VAF) of 0.5% in the reference samples and VAFs that were highly concordant with previous digital droplet PCR results in the patient samples. At reduced input amounts (20, 15, and 5 ng) and below VAFs of 0.5%, sensitivity was considerably lower and variant detection variability increased. Covering 523 tumor-associated genes, the assay demonstrated a convincing performance comparable to NGS-based ctDNA assays with smaller gene panels, highlighting its value to screen large numbers of different genes.


Demograhic pattern, clinical features and treatment outcome of patients with infective keratitis in the eastern region of Nepal.
corneal ulcer is one of the major causes of monocular blindness in developing countries. to determine demographic pattern, risk factors, microbiological pattern and treatment outcome of infective keratitis. a retrospective analysis of hospital records of 44 patients with clinically-diagnosed infective keratitis presenting to B.P. Koirala Institute of Health Sciences in the eastern region of Nepal was carried out. the parameters studied were risk factors and organisms responsible for keratitis. the infective keratitis was mostly prevalent among the males between 21-40 years of age (50%). 79.5 % of them were engaged in agricultural work. Ahistory of corneal injury was found in 30 eyes (68.1%). Vegetative matter was the most common agent of trauma in 17 (56.6%). Culture positivity for microorganisms was observed in 20 (45.5%) samples. Of these, 8 (40%) patients had purely bacterial corneal ulcer. Purely fungal growth was seen in 4 (20%) and mixed in 8 (40%). Staphylococcus aureus was the most commonly isolated bacteria (70%). The other bacteria included Pseudomonas species, E. coli and Acinetobactor. Aspergillus species was the most common fungal organism isolated in 8 (40%) samples. 65.9 % of the patients improved with medical treatment alone. Perforation, endophthalmitis and panophthalmitis were the common complications encountered in 11.3%, 4.5% and 4.5% respectively. corneal ulcer is prevalent in males, predominantly amongst the farmers. Ocular trauma with vegetative matter is the commonest predisposing factor. Staphylococcus aureus and Aspergillus species are the most commonly isolated organisms in corneal ulcers.


Gene x environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict.
Serotonin genes have been hypothesized to play a role in the etiology of attention-deficit hyperactivity disorder (ADHD); prior work suggests that serotonin may interact with psychosocial stressors in ADHD, perhaps via mechanisms involved in emotional dysregulation. Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR) on liability for ADHD. 304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls. Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC) scale to assess appraisals of self-blame in relation to their parents' marital disputes. The trialleic configuration of 5HTTLPR (long/short polymorphism with A> G substitution) was genotyped and participants were assigned as having high (La/La N = 78), intermediate (La/Lg, La/short, N = 137), or low (Lg/Lg, Lg/short, short/short, N = 89) serotonin transporter activity genotypes. Teacher reported behavior problems were examined as the target outcome to avoid informant overlap for moderator and outcome measures. Hierarchical linear regression analyses indicated significant 5HTTLPR x self-blame interactions for ADHD symptoms. Examination of the interactions indicated positive relations between reports of self-blame and ADHD symptoms for those with the high and low serotonin activity genotypes. There was no relation between self-blame and ADHD for those with intermediate activity 5HTTLPR genotypes. Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to inter-parental conflict. Results are discussed in relation to the role of serotonin in the etiology of the ADHD and related externalizing behaviors.


On the Role of Different Age Groups and Pertussis Vaccines During the 2012 Outbreak in Wisconsin.
There is limited information on the roles of different age groups in propagating pertussis outbreaks, and on the impact of vaccination on pertussis transmission in the community. The relative roles of different age groups in propagating the 2012 pertussis outbreak in Wisconsin were evaluated using the relative risk (RR) statistic that measures the change in the group's proportion among all detected cases before vs after the epidemic peak. The impact of vaccination in different age groups against infection (that is potentially different from the protective effect against detectable disease) was evaluated using the odds ratios (ORs), within each age group, for being vaccinated vs undervaccinated before vs after the outbreak's peak. The RR statistic suggests that children aged 13-14 years played the largest relative role during the outbreak's ascent (with estimates consistent across the 3 regions in Wisconsin that were studied), followed by children aged 7-8, 9-10, and 11-12 years. Young children and older teenagers and adults played more limited relative roles during the outbreak. Results of the vaccination status analysis for the fifth dose of DTaP (for children aged 7-8 years: OR, 0.44; 95% confidence interval [CI], 0.23-0.86; for children aged 9-10 years: OR, 0.51; 95% CI, 0.27-0.95); and for Tdap for children aged 13-14 years (OR, 0.38, 95% CI, 0.16-0.89) are consistent with protective effect against infection. While our epidemiological findings for the fifth dose of DTaP and for Tdap are consistent with protective effect against infection, further studies, including those estimating vaccine effectiveness against infection/transmission to others particularly for pertussis vaccines for adolescents, are needed to evaluate the impact of vaccination on the spread of pertussis in the community.


Selective silencing of angiotensin receptor subtype 1a (AT1aR) by RNA interference.
Angiotensin II exerts its physiological effects by activating multiple subtypes of its receptor such as AT1a-, AT1b-, and AT2-receptors. Because of a high degree of similarity among these G-protein-coupled receptors, it has been difficult to assign diverse physiological actions of angiotensin II through these receptor subtypes. We have developed small interfering RNAs to selectively inhibit the expression of the AT1a receptor (AT1aR) subtype. A dsRNA, AT1 47, was found to be highly selective and efficient in reducing the levels of AT1aR subtype. Transfection of AT1aR-expressing CHO cells with dsRNA AT1 47 resulted in an 80% decrease in the AT1aR expression. In contrast, dsRNA AT1 47 showed no significant effects on both AT1bR and AT2R subtypes. Thus, AT1 47 provides us with a powerful tool to selectively silence this subtype of receptor to investigate its role in cardiovascular physiology.


NKG2D is critical for NK cell activation in host defense against Pseudomonas aeruginosa respiratory infection.
Pseudomonas aeruginosa is a major cause of nosocomial respiratory infections. The eradication of P. aeruginosa from the lung involves the orchestrated actions of the pulmonary epithelium and both resident and recruited immune cells. The NKG2D receptor is constitutively expressed on the surface of circulating and tissue-resident NK cells (and other cytotoxic lymphocytes), and is capable of controlling NK cell activation and production of cytokines, such as IFN-gamma via interactions with ligands expressed on the surface of stressed cells. Previously, we demonstrated that NKG2D mediates pulmonary clearance of P. aeruginosa. In the present study, we investigated the cellular and molecular mechanisms of NKG2D-mediated clearance of P. aeruginosa using a novel transgenic mouse model of doxycycline-inducible conditional expression of NKG2D ligands (retinoic acid early transcript 1, alpha) in pulmonary epithelial cells. NKG2D ligand expression in this model increased pulmonary clearance, cellular phagocytosis, and survival following P. aeruginosa respiratory infection. Additionally, NK cell sensitivity to ex vivo LPS stimulation was greater in lung cells isolated from naive transgenic mice administered doxycycline. We also showed that NK cells are the primary source of lymphocyte-derived IFN-gamma in response to P. aeruginosa respiratory infection. Significantly, we demonstrated that NKG2D is critical to the nonredundant IFN-gamma production by pulmonary NK cells following acute P. aeruginosa infection. These results represent the principal report of NKG2D-mediated activation of lung NK cells following respiratory infection with an opportunistic pathogen and further establish the importance of NKG2D in the host response against P. aeruginosa respiratory infection.


Transcriptional regulation of dosage compensation in Carica papaya.
Sex chromosome evolution results in the disparity in gene content between heterogametic sex chromosomes and creates the need for dosage compensation to counteract the effects of gene dose imbalance of sex chromosomes in males and females. It is not known at which stage of sex chromosome evolution dosage compensation would evolve. We used global gene expression profiling in male and female papayas to assess gene expression patterns of sex-linked genes on the papaya sex chromosomes. By analyzing expression ratios of sex-linked genes to autosomal genes and sex-linked genes in males relative to females, our results showed that dosage compensation was regulated on a gene-by-gene level rather than whole sex-linked region in papaya. Seven genes on the papaya X chromosome exhibited dosage compensation. We further compared gene expression ratios in the two evolutionary strata. Y alleles in the older evolutionary stratum showed reduced expression compared to X alleles, while Y alleles in the younger evolutionary stratum showed elevated expression compared to X alleles. Reduced expression of Y alleles in the older evolutionary stratum might be caused by accumulation of deleterious mutations in regulatory regions or transposable element-mediated methylation spreading. Most X-hemizygous genes exhibited either no or very low expression, suggesting that gene silencing might play a role in maintaining transcriptional balance between females and males.


Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.
Psilocybin shows promise as a treatment for major depressive disorder (MDD). To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. ClinicalTrials.gov Identifier: NCT03866174.


Altered lipid metabolism in gastroschisis: a novel hypothesis.
Gastroschisis is a congenital abdominal wall defect where there is herniation of abdominal organs. Optimal maternal nutritional intake, in particular, fatty acids, are vital for proper growth and development of the fetus. This pilot case-control study explored the association of several biomarkers of fatty acids and gastroschisis. Between 2008 and 2011, we recruited 13 pregnant women in mid-gestation who were referred to the UCSD Prenatal Center for evaluation of an abnormal maternal serum alpha-fetoprotein (MSAFP) test and subsequently identified as carrying a baby with gastroschisis. Nine controls were selected from a false positive MSAFP or from the UCSD prenatal clinic. At enrollment, maternal blood was drawn for analysis of fatty acids. Mann-Whitney-Wilcoxon tests were used to test for mean differences between erythrocyte fatty acid biomarkers and the fatty acid lipogenic (palmitic acid: linoleic acid) and desaturation (palmitoleic acid: palmitic acid) indices and gastroschisis. Mothers carrying a baby with gastroschisis and gastroschisis babies had consistently higher levels of palmitoleic acid (all P's < 0.05), gastroschisis mothers had lower levels of oleic acid during pregnancy and at delivery, and higher levels of DHA at delivery (all P's < 0.05). The lipogenic index was significantly lower at delivery for gastroschisis mothers (P < 0.05) and the desaturation index was consistently higher in gastroschisis mothers and babies (all P's < 0.01). These findings suggest that early maternal inflammation possibly resulting from an imbalance of fatty acids, leading to a vascular disruption, may be the underlying mechanism responsible for at least some cases of gastroschisis.


Fair Allocation of Scarce Therapies for Coronavirus Disease 2019 (COVID-19).
The US Food and Drug Administration (FDA) has issued emergency use authorizations (EUAs) for monoclonal antibodies (mAbs) for nonhospitalized patients with mild or moderate coronavirus disease 2019 (COVID-19) disease and for individuals exposed to COVID-19 as postexposure prophylaxis. EUAs for oral antiviral drugs have also been issued. Due to increased demand because of the Delta variant, the federal government resumed control over the supply and asked states to ration doses. As future variants (eg, the Omicron variant) emerge, further rationing may be required. We identify relevant ethical principles (ie, benefiting people and preventing harm, equal concern, and mitigating health inequities) and priority groups for access to therapies based on an integrated approach to population health and medical factors (eg, urgently scarce healthcare workers, persons in disadvantaged communities hard hit by COVID-19). Using priority categories to allocate scarce therapies effectively operationalizes important ethical values. This strategy is preferable to the current approach of categorical exclusion or inclusion rules based on vaccination, immunocompromise status, or older age, or the ad hoc consideration of clinical risk factors.


pKBuS13, a KPC-2-encoding plasmid from Klebsiella pneumoniae sequence type 833, carrying Tn4401b inserted into an Xer site-specific recombination locus.
Here, we report the first detection of a Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing Klebsiella pneumoniae strain belonging to sequence type 833 (ST833), collected in an Italian hospital from a patient coming from South America. Its bla KPC determinant was carried by a ColE1 plasmid, pKBuS13, that showed the Tn4401b::bla KPC-2 transposon inserted into the regulatory region of an Xer site-specific recombination locus. This interfered with the correct resolution of plasmid multimers into monomers, lowering plasmid stability and leading to overestimation of the number of plasmids harbored by a single host cell. Sequencing of the fragments adjacent to Tn4401b detected a region that did not have significant matches in databases other than the genome of a carbapenem-resistant Escherichia coli strain collected during the same year at a hospital in Boston. This is interesting in an epidemiologic context, as it suggests that despite the absence of tra genes and the instability under nonselective conditions, the circulation of pKBuS13 or of analogous plasmids might be wider than reported.


Development and characterization of a new muscle cell culture system from Clarias magur (Hamilton, 1822).
The cell line has been used as a novel in vitro tool for executing several studies in life sciences. The current study aimed to develop and characterize a muscle cell culture system derived from Clarias magur. The primary muscle cell cultures derived from the caudal peduncle muscle have been successfully sub cultured up to 13 passages to establish a new muscle cell culture system known as CMM. At a temperature of 28 °C, L-15 medium supplemented with 20% FBS produced the maximum growth of muscle cells. However, muscle cells were optimized to grow at 10% FBS. To enhance the proliferation capacity of the CMM cells, a growth-promoting factor bFGF (10 ng/ml) was added, thereby reducing the time interval of passages for the subsequent cultures. DNA barcoding of the CMM cell culture system authenticated the species of origin. The cell culture system was successfully cryopreserved by a slow freezing procedure at - 80 °C with a revival efficiency of 60%.


[Microbiocenosis of oral cavity in patients from different age groups].
Worsening of state of oral cavity is observed not only in elderly persons, but also in adults aswell as in adolescents and children. The leading role in development of dental caries and periodontal diseases belongs to microorganisms. Oral cavity bacterial landscape was determined in adolescents, adults and elderly people with normal periodont or with gingivitis or periodontitis. The study showed that species and qualitative composition of oral cavity microflora were different in different age groups. In patients with normal periodont, non pathogenic (common commensals) microbial composition was revealed. In abnormal state of oral cavity, its microflora was characterized by the presence of high titers of potentiality pathogenic microorganisms.


The role of calcium stores in apoptosis and autophagy.
The mechanisms that regulate programmed cell death, such as apoptosis, and the cellular "self-eating" phenomenon of autophagy, share many regulatory systems and common pathways. These mechanisms have been extensively investigated over the last few years. Some intracellular structures may determine and control the autophagic fate of the cell such as the endoplasmic reticulum, mitochondria, and lysosomes. The coordination and interrelation of these organelles are crucial in maintaining calcium levels and general cellular homeostasis, as well as in regulating cell life and death under physiological and pathological conditions, including cancer, neurodegeneration, and aging. In this review, we discuss the crosstalk between the aforementioned organelles and their influence in apoptotic and autophagic processes.


Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP.
Class I metabotropic glutamate receptors (mGluRs) have been postulated to play a role in synaptic plasticity. To test the involvement of one member of this class, we have recently generated mutant mice that express no mGluR5 but normal levels of other glutamate receptors. The CNS revealed normal development of gross anatomical features. To examine synaptic functions we measured evoked field EPSPs in the hippocampal slice. Measures of presynaptic function, such as paired pulse facilitation in mutant CA1 neurons, were normal. The response of mutant CA1 neurons to low concentrations of (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) was missing, which suggests that mGluR5 may be the primary high affinity ACPD receptor in these neurons. Long-term potentiation (LTP) in mGluR5 mutants was significantly reduced in the NMDA receptor (NMDAR)-dependent pathways such as the CA1 region and dentate gyrus of the hippocampus, whereas LTP remained intact in the mossy fiber synapses on the CA3 region, an NMDAR-independent pathway. Some of the difference in CA1 LTP could lie at the level of expression, because the reduction of LTP in the mutants was no longer observed 20 min after tetanus in the presence of 2-amino-5-phosphonopentanoate. We propose that mGluR5 plays a key regulatory role in NMDAR-dependent LTP. These mutant mice were also impaired in the acquisition and use of spatial information in both the Morris water maze and contextual information in the fear-conditioning test. This is consistent with the hypothesis that LTP in the CA1 region may underlie spatial learning and memory.


Evaluation of large-scale dissemination of Nosema ceranae spores by European bee-eaters Merops apiaster.
Identification of transmission routes and of factors affecting the spatial positions of pathogens, hosts and vectors is basic to an adequate disease management. Nosema ceranae is a Microsporidian recently described as a parasite of Apis mellifera honeybees and is currently considered the aetiological agent of an emergent illness named nosemosis type C. In this article we evaluate the role of a bird species, the European bee-eater, Merops apiaster, as a large-scale dispersive agent of N. ceranae. We found a high prevalence of viable spores of N. ceranae in pellets regurgitated by bee-eaters in different locations in the Iberian Peninsula, Central Europe and central Asia. In contrast, spores of Nosema apis, considered till recently the most common microsporidium infecting honeybees, were detected in a single locality and Nosema bombi spores were not noticed. Since non-viable spores were also found in bee-eater nests from different locations, this bird species could also reduce the fraction of infected insects by withdrawing pathogens from the colonies. We conclude that bee-eater mobility and migration may have played an important role in the transmission of the pathogen N. ceranae.


Purification and characterization of benzoate-CoA ligase from Magnetospirillum sp. strain TS-6 capable of aerobic and anaerobic degradation of aromatic compounds.
Benzoate-CoA ligase (EC 184.108.40.206), the initial enzyme of anaerobic benzoate degradation, was purified and characterized from Magnetospirillum sp. strain TS-6 grown under both anaerobic and aerobic conditions. The enzyme purified from anaerobically grown cells was a homodimer with a relative molecular mass of 120 kDa. The specific activity for benzoyl-CoA synthesis was 13.4 micromol min(-1) mg(-1) protein. The enzyme purified from aerobically grown cells was concluded to be the same gene product as the anaerobic enzyme. The benzoate-CoA ligase gene consisting of 1587 nucleotides was cloned and sequenced, and its induction under aerobic and anaerobic conditions during growth on benzoate was confirmed by quantitative reverse transcription PCR. These results indicate that a single benzoate-CoA ligase is expressed and benzoate is converted into benzoyl-CoA under both aerobic and anaerobic conditions in Magnetospirillum sp.


Changes in the structure and function of northern Alaskan ecosystems when considering variable leaf-out times across groupings of species in a dynamic vegetation model.
The phenology of arctic ecosystems is driven primarily by abiotic forces, with temperature acting as the main determinant of growing season onset and leaf budburst in the spring. However, while the plant species in arctic ecosystems require differing amounts of accumulated heat for leaf-out, dynamic vegetation models simulated over regional to global scales typically assume some average leaf-out for all of the species within an ecosystem. Here, we make use of air temperature records and observations of spring leaf phenology collected across dominant groupings of species (dwarf birch shrubs, willow shrubs, other deciduous shrubs, grasses, sedges, and forbs) in arctic and boreal ecosystems in Alaska. We then parameterize a dynamic vegetation model based on these data for four types of tundra ecosystems (heath tundra, shrub tundra, wet sedge tundra, and tussock tundra), as well as ecotonal boreal white spruce forest, and perform model simulations for the years 1970-2100. Over the course of the model simulations, we found changes in ecosystem composition under this new phenology algorithm compared with simulations with the previous phenology algorithm. These changes were the result of the differential timing of leaf-out, as well as the ability for the groupings of species to compete for nitrogen and light availability. Regionally, there were differences in the trends of the carbon pools and fluxes between the new phenology algorithm and the previous phenology algorithm, although these differences depended on the future climate scenario. These findings indicate the importance of leaf phenology data collection by species and across the various ecosystem types within the highly heterogeneous Arctic landscape, and that dynamic vegetation models should consider variation in leaf-out by groupings of species within these ecosystems to make more accurate projections of future plant distributions and carbon cycling in Arctic regions.


The NLRP3 inflammasome promotes renal inflammation and contributes to CKD.
Inflammation significantly contributes to the progression of chronic kidney disease (CKD). Inflammasome-dependent cytokines, such as IL-1β and IL-18, play a role in CKD, but their regulation during renal injury is unknown. Here, we analyzed the processing of caspase-1, IL-1β, and IL-18 after unilateral ureteral obstruction (UUO) in mice, which suggested activation of the Nlrp3 inflammasome during renal injury. Compared with wild-type mice, Nlrp3(-/-) mice had less tubular injury, inflammation, and fibrosis after UUO, associated with a reduction in caspase-1 activation and maturation of IL-1β and IL-18; these data confirm that the Nlrp3 inflammasome upregulates these cytokines in the kidney during injury. Bone marrow chimeras revealed that Nlrp3 mediates the injurious/inflammatory processes in both hematopoietic and nonhematopoietic cellular compartments. In tissue from human renal biopsies, a wide variety of nondiabetic kidney diseases exhibited increased expression of NLRP3 mRNA, which correlated with renal function. Taken together, these results strongly support a role for NLRP3 in renal injury and identify the inflammasome as a possible therapeutic target in the treatment of patients with progressive CKD.


Interpolation from samples on a linear spiral scan.
An interpolation method useful for reconstructing an image from its Fourier plane samples on a linear spiral scan trajectory is presented. This kind of sampling arises in NMR imaging. We first present a theorem that enables exact interpolation from spiral samples to a Cartesian lattice. We then investigate two practical implementations of the theorem in which a finite number of interpolating points are used to calculate the value at a new point. Our experimental results confirm the theorem's validity and also demonstrate that both practical implementations yield very good reconstructions. Thus, the theorem and/or its practical implementations suggest the possibility of using direct Fourier reconstruction from linear spiral-scan NMR imaging.


Polyvinyl alcohol and gelatin sponge particle embolization of splenic artery pseudoaneurysm complicating chronic alcoholic pancreatitis.
To assess the effectiveness of and complications associated with polyvinyl alcohol (PVA) and gelatin sponge particles embolization of splenic artery pseudoaneurysm complicating chronic alcoholic pancreatitis. A 42-year-old man with splenic artery pseudo-aneurysm formation secondary to chronic alcoholic pancreatitis was admitted. We used PVA and gelatin sponge particles embolization of splenic artery pseudoaneurysm by superselective embolization techniques. The splenic artery pseudoaneurysm was successfully controlled with splenic embolization. The patient was discharged in 9 d with complete recovery. This case confirms that superselective transcatheter embolization by PVA and gelatin sponge particles may represent an effective treatment for pseudoaneurysm caused by chronic alcoholic pancreatitis in the absence of other therapeutic alternatives.


Spatial and temporal changes in genetic structure of greenhouse and field populations of cabbage looper, Trichoplusia ni.
Trichoplusia ni is a subtropical moth that migrates annually from southern California to southern British Columbia, Canada where it invades vegetable greenhouses and field crops. The heated greenhouse environment has altered the natural extinction-recolonization dynamics of T. ni populations, and allows year-round persistence in some locations. In addition, the extensive use of the biopesticide, Bacillus thuringiensis subspecies kurstaki (Bt) in some greenhouses has selected for resistance. Here we investigated the genetic structure of T. ni populations in British Columbia greenhouses and in field populations in California and British Columbia using amplified fragment length polymorphisms (AFLP) as related to patterns of Bt resistance. The majority of British Columbia field populations were similar to the California field populations, the potential source of migrants. However populations in two geographic areas with high concentrations of greenhouses showed local genetic differentiation. Some of these populations experienced severe bottlenecks over-winter and following Bt sprays. Greenhouse populations showed a pattern of isolation by distance and a strong positive relationship between genetic differentiation and levels of Bt resistance. These patterns indicate that greenhouses that sometimes support year-round populations of T. ni and the ensuing strong bottlenecking effects following winter cleanups and Bt application cause genetic differentiation of T. ni populations. Long distance migrants to field populations contribute to genetic homogeneity of these.


Prosthodontic decision making among general dentists in Sweden. III: The choice between fixed partial dentures and single implants.
The purpose of this study was to describe how dentists evaluated the importance of various items related to a treatment choice between fixed partial dentures (FPD) and single implants, and to analyze if the differences could be explained by dentist-related variables such as social and demographic attributes, job situation, and attitudes. Questionnaires were sent to a random sample of 2,059 Swedish general dentists, with a response rate of 76%. In the questionnaire, the choice between an FPD and a single-implant restoration in a clinical situation was presented. Fifteen items were constructed and the dentists were asked to mark on visual analogue scales the relative importance he or she gave the different items. The items were analyzed through principal components analysis, where a three-factor solution was obtained; the factors were labeled as "time," "health," and "comfort." The factors were run as dependent variables in multiple regression analyses. The items evaluated as most important were "prognosis for delivered treatment" and "patient's wish." Large individual differences were seen, but the differences between groups of dentists were small. Male dentists considered the "health" and the "comfort" factors to be more important compared to female dentists. The attitudinal variable "patient information" was significantly associated with the "time" factor and, inversely, with the "comfort" factor. Differences between individuals were great, but between groups of dentists the differences were only minor. Multivariately, the attitudinal variable "patient information" showed significant associations with the "time" and the "comfort" factors. Dentist-related variables explained little of the variations. The results further indicated a low personal knowledge concerning implant treatments. Psychologic methods might explain more of the individual differences in prosthodontic decision making, but these are not easily used in a questionnaire study.


HyLength: a semi-automated digital image analysis tool for measuring the length of roots and fungal hyphae of dense mycelia.
In plant-fungus phenotyping, determining fungal hyphal and plant root lengths by digital image analysis can reduce labour and increase data reproducibility. However, the degree of software sophistication is often prohibitive and manual measuring is still used, despite being very time-consuming. We developed the HyLength tool for measuring the lengths of hyphae and roots in in vivo and in vitro systems. The HyLength was successfully validated against manual measures of roots and fungal hyphae obtained from all systems. Compared with manual methods, the HyLength underestimated Medicago sativa roots in the in vivo system and Rhizophagus irregularis hyphae in the in vitro system by about 12 cm per m and allowed to save about 1 h for a single experimental unit. As regards hyphae of R. irregularis in the in vivo system, the HyLength overestimated the length by about 21 cm per m compared with manual measures, but time saving was up to 20.5 h per single experimental unit. Finally, with hyphae of Aspergillus oryzae, the underestimation was about 8 cm per m with a time saving of about 10 min for a single germinating spore. By benchmarking the HyLength against the AnaMorf plugin of the ImageJ/Fiji, we found that the HyLength performed better for dense fungal hyphae, also strongly reducing the measuring time. The HyLength can allow measuring the length over a whole experimental unit, eliminating the error due to sub-area selection by the user and allowing processing a high number of samples. Therefore, we propose the HyLength as a useful freeware tool for measuring fungal hyphae of dense mycelia.


How well do ITS rDNA sequences differentiate species of true morels (Morchella)?
Arguably more mycophiles hunt true morels (Morchella) during their brief fruiting season each spring in the northern hemisphere than any other wild edible fungus. Concerns about overharvesting by individual collectors and commercial enterprises make it essential that science-based management practices and conservation policies are developed to ensure the sustainability of commercial harvests and to protect and preserve morel species diversity. Therefore, the primary objectives of the present study were to: (i) investigate the utility of the ITS rDNA locus for identifying Morchella species, using phylogenetic species previously inferred from multilocus DNA sequence data as a reference; and (ii) clarify insufficiently identified sequences and determine whether the named sequences in GenBank were identified correctly. To this end, we generated 553 Morchella ITS rDNA sequences and downloaded 312 additional ones generated by other researchers from GenBank using emerencia and analyzed them phylogenetically. Three major findings emerged: (i) ITS rDNA sequences were useful in identifying 48/62 (77.4%) of the known phylospecies; however, they failed to identify 12 of the 22 species within the species-rich Elata Subclade and two closely related species in the Esculenta Clade; (ii) at least 66% of the named Morchella sequences in GenBank are misidentified; and (iii) ITS rDNA sequences of up to six putatively novel Morchella species were represented in GenBank. Recognizing the need for a dedicated Web-accessible reference database to facilitate the rapid identification of known and novel species, we constructed Morchella MLST (http://www.cbs.knaw.nl/morchella/), which can be queried with ITS rDNA sequences and those of the four other genes used in our prior multilocus molecular systematic studies of this charismatic genus.