Parathyroid carcinoma: evaluation and interdisciplinary management.
A review of recent reports found a distinct clinical behavior pattern in the rare clinical entity of parathyroid carcinoma, although to the authors' knowledge information on oncogenetic changes, prognostic factors, and the potential benefits of adjuvant therapy remain fragmented and scarce. In this report, a composite review of the literature and The University of Texas M. D. Anderson Cancer Center (M. D. Anderson) experience are presented using the presentation of a patient to illustrate critical issues in the evaluation and interdisciplinary management of patients who are afflicted with this disease. The current study reflects a retrospective case review of patients who were diagnosed with parathyroid carcinoma, treated, and followed at M. D. Anderson from 1983 to 2002. To assure standardization of pathologic diagnosis as well as evaluations and interdisciplinary management, the investigators reviewed all cases using predetermined criteria within their specialties. It is interesting to note that M. D. Anderson data showed classic pathologic features that were not always present in all parathyroid carcinomas (at most, some features were noted in 37% of patients). Other results of interest indicated local recurrence rates that appeared lower if adjuvant radiation was applied after initial surgery, independent of the type of surgery or disease stage. In the authors' experience, 70% of patient's tumors exhibited local invasion, although their 5-year survival rate of 85% was consistent with that reported previously, and their 10-year survival rate was somewhat higher at 77%. Parathyroid carcinoma is a rare clinical entity that requires interdisciplinary evaluation and management. Comprehensive surgical excision of parathyroid carcinomas with verification of normalization of intraoperative parathyroid hormone levels should be sought.


Preseason Baseline Neurocognitive Performances and Symptom Reporting on Immediate Post-Concussion Assessment and Cognitive Testing: A Comparison of Adolescent Student-Athletes Tested in Spanish and English.
Student-athletes are commonly administered the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery at preseason baseline and postconcussion. The ImPACT is available in many languages, but few researchers have examined differences in cognitive performances and symptom ratings based on the language of administration. To examine differences in ImPACT neurocognitive composites and symptom reporting at preseason baseline testing between student-athletes who completed ImPACT in Spanish versus English. Cross-sectional study. Preseason baseline testing for a high school concussion-management program in Maine. Adolescent student-athletes who completed testing in Spanish (n = 169) and English (n = 169) were matched on age, gender, and health and academic history. Language groups were compared on each outcome for the full sample and for gender-stratified subsamples. Neurocognitive composite scores and individual and total symptom severity ratings from the ImPACT battery. Athletes tested in Spanish displayed lower levels of neurocognitive performance on 2 of 5 composite scores (visual motor speed: P < .001, d = 0.51; reaction time: P = .004, d = 0.33) and reported greater symptom severity (P < .001, r = 0.21). When the analyses were stratified by gender, similar visual motor speed differences were observed between language groups among boys (P = .001, d = 0.49) and girls (P = .001, d = 0.49), whereas reaction time showed a larger group difference for boys (P = .012, d = 0.42) than for girls (P = .128, d = 0.21). Language-group differences in symptom reporting were similar for boys (P = .003, r = 0.22) and girls (P = .008, r = 0.21), with more frequent endorsement of physical and affective symptoms by athletes tested in Spanish. Language-group differences in total symptom severity were small (r = 0.21) and in neurocognitive performances were small to medium (d = 0.05-0.51). Versus previous authors who compared athletes tested in Spanish and English with ImPACT, we observed smaller effects, which may be attributable to close matching on variables related to neurocognitive performances and symptom reporting.


Laser nano-filament explosion for enabling open-grating sensing in optical fibre.
Embedding strong photonic stopbands into traditional optical fibre that can directly access and sense the outside environment is challenging, relying on tedious nano-processing steps that result in fragile thinned fibre. Ultrashort-pulsed laser filaments have recently provided a non-contact means of opening high-aspect ratio nano-holes inside of bulk transparent glasses. This method has been extended here to optical fibre, resulting in high density arrays of laser filamented holes penetrating transversely through the silica cladding and guiding core to provide high refractive index contrast Bragg gratings in the telecommunication band. The point-by-point fabrication was combined with post-chemical etching to engineer strong photonic stopbands directly inside of the compact and flexible fibre. Fibre Bragg gratings with sharply resolved π-shifts are presented for high resolution refractive index sensing from [Formula: see text] = 1 to 1.67 as the nano-holes were readily wetted and filled with various solvents and oils through an intact fibre cladding.


Phycoremediation of milk processing wastewater and lipid-rich biomass production using Chlorella vulgaris under continuous batch system.
This study compiles the results of phycoremediation of milk processing wastewater (MPWW) and production of lipid-rich Chlorella vulgaris biomass using a continuous batch system operated for 12-wks. After a 4-wks interval, a new MPWW was loaded photobioreactor to provide appropriate nutrient supply to algae. Results indicated that MPWW supported the algal growth efficiently and the maximum algal growth was recorded in the ranges of 400.36 to 421.58 mg L-1 during 4-wk's of the cultivation cycle. Average reduction in total nitrogen, TN (45.82-69.18%); nitrate, NO3 (93.32-94.54%); total ammonium nitrogen, TAN (92.94-94.54%); sulphate, SO4-2 (85.13-87.34%); total phosphorus (75.09-78.78%); and biochemical oxygen demands, BOD (89.53-92.40%) was recorded during 12-wks phycoremediation of MPWW. Harvested algal biomass (dry weight basis, DW) exhibited a significant content of total sugar (45.5%) and total lipid (39.7%). The lipid profiling results indicated the presence of palmitic acid (39.9%), oleic acid (21.08%), linoleic acid (13.13%), and other C18 compounds in algal biomass, suggesting the suitability of MPWW for Chlorella vulgaris cultivations. Algal biomass exhibited a high heating value (MJ/Kg of DW) in the range of 17.3 to 25.1, comparable to other lignocellulose biomass to be used for bioenergy purposes. Results of this study indicate that MPWW could be utilized as a valuable medium for Chlorella vulgaris cultivation under a circular economy approach: wastewater treatment and bioenergy feedstock production. The effect of controlled environmental conditions on algal growth behavior and lipid composition in biomass, while using MPWW as a medium, could be investigated in future studies.


Protein targeting into plastids: a key to understanding the symbiogenetic acquisitions of plastids.
Recent progress in molecular phylogenetics has proven that photosynthetic eukaryotes acquired plastids via primary and secondary endosymbiosis and has given us information about the origin of each plastid. How a photosynthetic endosymbiont became a plastid in each group is, however, poorly understood, especially for the organisms with secondary plastids. Investigating how a nuclear-encoded plastid protein is targeted into a plastid in each photosynthetic group is one of the most important keys to understanding the evolutionary process of symbiogenetic plastid acquisition and its diversity. For organisms which originated through primary endosymbiosis, protein targeting into plastids has been well studied at the molecular level. For organisms which originated through secondary endosymbiosis, molecular-level studies have just started on the plastid-targeted protein-precursor sequences and the targeting pathways of the precursors. However, little information is available about how the proteins get across the inner two or three envelope membranes in organisms with secondary plastids. A good in vitro protein-import system for isolated plastids and a cell transformation system must be established for each group of photosynthetic eukaryotes in order to understand the mechanisms, the evolutionary processes and the diversity of symbiogenetic plastid acquisitions in photosynthetic eukaryotes.


[Rectal cancer update: postneoadjuvant staging].
Over the last two decades, magnetic resonance imaging (MRI) has continuously been gaining influence in modern management of rectal cancer. Bringing morphological and functional features together improves the differentiation of responders from nonresponders, provides for accurate surgical planning, intensified radiation therapy regimes, and watch-and-wait strategies. A shift from TNM staging towards risk stratification of rectal cancer patients, patient selection to increasingly individualized therapies, and intensified surveillance has contributed to the transformation of rectal MRI into a true gamechanger.


Guarding food safety with conventional and up-conversion near-infrared fluorescent sensors.
Acknowledged by the World Health Organisation (WHO), over 200 diseases ranging from mild to fatal are linked to the consumption of food products subjected to physical, chemical, or biological contamination. Nevertheless, conventional methods commonly used for the identification of health hazards in foodstuffs have problems coping with the sensitivity requirements imposed by latest-hour regulations in the field. Additionally, their use and availability is wildly limited by aspects such as instrument dimension, prohibitive costs, detection complexity and required operational knowledge. This review provides an overview of recent efforts that have focused on the assesment of food contamination based on near infrared (NIR) photoluminescent sensors. Important endeavors that have targeted the precise detection of various inorganic and organic contaminants, including hydrogen sulfide, cyanide anions, mycotoxins, antibiotic residues, etc., are presented and relevant challenges that lie en route as stumbling blocks for such sensors to reach the next level of maturity and to become more available, are systematically discussed and enunciated. Ingenious food contamination sensors that rely on conventional or up-conversion photoluminescence in the NIR region represent an emerging topic. To date, such sensors have been demonstrated as promising detection candidates, possessing important advantages such as: high efficiency, facile implementation, and convenient flexibility, thereby promising significant contributions to expand the current state of the art in food security.


Tail injuries increase the risk of mortality in free-living lizards (Uta stansburiana).
Caudal autotomy is an effective anti-predator mechanism used by many lizard species. Fitness benefits of surviving a predatory attack are obvious, although lizards that autotomize their tails may be at greater risk during subsequent encounters with predators than lizards with complete tails. In previous laboratory studies, tail-less lizards were more vulnerable to capture by predators, but little is known about the relative survival of tailed versus tail-less lizards in nature. This study reports on significant associations between naturally incurred tail injuries and the subsequent risk of mortality in 7 populations of the lizard Uta stansburiana. I used standard mark-recapture techniques to document survival and quantified tail injuries by estimating tail completeness. I then used sampled randomization tests to compare intitial tail completeness values of surviving versus non-surviving lizards. I evaluated overall patterns by comparising the means of tail completeness values of survivors versus non-survivors among mark-recapture sequences. Lizards with incomplete tails suffered higher mortality in the field, although this was not true for every comparison considered (i.e., for every mark-recapture sequence analyzed), and the overall trend was much stronger for adult males than for either adult females or juveniles. Higher mortality among lizards with incomplete tails is presumably a consequence of increased vulnerability to capture by predators. Vulnerability to predation of tail-injured lizards may be confounded by reduced social status in this species, because social subordination can result in the occupation of an inferior home range.


Membrane lipid, not polarized water, is responsible for the semipermeable properties of living cells.
It has recently been proposed that the semipermeable surface barrier of living cells is in fact provided by water polarized in multilayers by the cellular protein, and not by the lipids of the cell membrane as had been widely supposed. This review paper summarizes a large and diverse body of recent experimental work, concerned with the structure and function of biological membranes in general and with the passive permeability properties of cell surface membranes in particular, which does not support the polarized water hypothesis. Indeed, there exists a great deal of experimental evidence which supports the concept that the lipid bilayer is a central structural feature of cell surface membranes and that one of the major functions of this lipid bilayer is to provide the selective, semipermeable barrier found at the surface of living cells.


PM2.5 aggravates diabetes via the systemically activated IL-6-mediated STAT3/SOCS3 pathway in rats' liver.
PM2.5 exposure aggravates type 2 diabetes, in which inflammatory factors play an important role. In this study, we aimed to explore the mechanisms responsible for aggravating diabetes after PM2.5 exposure, and study the roles of inflammatory factors in insulin-resistant type 2 diabetes. Our study indicated that short-time PM2.5 exposure enhances insulin resistance in type 2 diabetic rats and significantly raises inflammatory factors, including IL-6, TNF-α, and MCP-1, in lungs. However, we found that of these inflammatory factors only IL-6 levels are elevated in blood, liver, adipose tissue, and macrophages, but not in skeletal muscle. IL-6 induced activation of the STAT3/SOCS3 pathway in liver, but not other downstream pathways including STAT1, ERK1/2, and PI3K. Both STAT3 inhibition and IL-6 neutralization effectively alleviated the disorders of glucose metabolism after PM2.5 exposure. Taken together, this suggests that the systemic increase in IL-6 may play an important role in the deterioration of the type 2 diabetes via IL-6/STAT3/SOCS3 pathway in liver after short-time exposure to PM2.5. Besides, we unexpectedly found a stronger resistance to the PM2.5 exposure-induced increase in IL-6 in skeleton muscle than those of many other tissues.


Psychoanalytic reconstructions and empirical data: reciprocal contributions.
Freud (1905, 1917, 1937) throughout his lifetime sought empirical scientific confirmation of the validity of his discoveries. In pursuit of this goal, he persistently emphasized the importance of establishing agreement between analytic reconstructions and the results of naturalistic child observation. The same objective lead Lichtenberg (1983), Emde (1981, 1985), and Stern (1985) to produce detailed evaluations of the impact of infant research findings on analytic developmental propositions. The present paper examines the relation among clinical reconstructions from an analysis developed through transference interpretations, empirical observations originating in the analytic patient's daughter's psychotherapy, and the results of empirical infant research that was being concurrently conducted by two of the authors. The findings from the clinical analysis of the mother, the psychotherapy of the daughter, and empirical infant research all converged on the same larger causative factor for the daughter's psychopathology--a type of maternal deprivation. Such a confluence of different sources of evidence, each identified by a different method of investigation, provides one kind of validation for psychoanalytic reconstructions, making it possible to provide that "satisfactory degree of certainty" which Freud (1937) called for in the attempt to integrate the patient's "psychic truth" with "actual" or historical truth.


Association of Genetic Polymorphisms in the VKORC1 and CYP2C9 Genes with Warfarin Dosage in a Group of Kuwaiti Individuals.
Warfarin is the most widely prescribed oral anticoagulant worldwide. The narrow therapeutic index and the large variation in the inter-individual dose of warfarin are problematic, since the side effects can be lethal. Single nucleotide polymorphisms (SNP) in CYP2C9 and VKORC1 have been shown to significantly affect warfarin dosage toleration and this effect varies among different populations. We aimed to investigate the effect of these SNPs on warfarin dosage in a sample of Kuwaiti patients. Kuwaiti patients who were taking a maintenance dose of warfarin were genotyped for CYP2C9*1, *2 and *3 and VKORC1 rs9923231, rs9934438, rs7294 and rs2884737. The association of these SNPs with the warfarin dose was evaluated. For CYP2C9, the CYP2C9 *1/*1 genotype required a higher dose (5.5 ± 3.3 mg/day) compared to non-*1/*1 (3.3 ± 1.7 mg/day) (p = 0.003). For VKORC1, the daily warfarin dose was significantly different (p = 0.001) among the three genotypes of rs9923231, rs9934438 and rs2884737, with carriers of the wild-type genotype requiring the highest dose compared to variant allele carriers (p ≤ 0.001-0.002). There was no association found between the daily warfarin dose and the rs7294 polymorphism. Our data showed that individuals carrying the wild-type allele of CYP2C9 or VKORC1 rs9923231, rs9934438 or rs2884737 are less sensitive than individuals with the variant alleles of these SNPs and therefore required a higher daily maintenance dose of warfarin. Our study confirms the association between SNPs in CYP2C9 and VKORC1 and warfarin dose tolerance in Kuwaiti patients.


A first test of elemental allelopathy via heterospecific pollen receipt.
Coflowering plants often share pollinators and may receive mixed species pollen loads. Although detrimental effects of heterospecific pollen receipt have been documented, trait-based modifiers of interactions on the stigma remain largely unknown. Chemicals that mediate interactions between sporophytes could also influence pollen-pollen or pollen-style interactions. We test for the first time whether nickel (Ni) accumulation in pollen can lead to "elemental allelopathy" and intensify the fitness consequences of heterospecific pollen receipt. We grew Ni-hyperaccumulator Streptanthus polygaloides in soils augmented with three concentrations of Ni, measured pollen Ni concentration, and hand-pollinated non-Ni hyperaccumulator Mimulus guttatus. We assayed pollen germination, tube growth and seeds of M. guttatus after pure and mixed species pollinations. Streptanthus polygaloides pollen accumulated Ni in proportion to soil availability and at levels significantly greater than M. guttatus pollen. Although receipt of S. polygaloides pollen increased M. guttatus pollen germination, it decreased the proportion of pollen tubes reaching the ovary and seed number. Increased Ni in pollen, however, did not significantly intensify the effect of S. polygaloides pollen receipt on M. guttatus seed production. Different levels of Ni in the pollen of S. polygaloides achieved in the greenhouse did not significantly reduce the fitness of M. guttatus. Stigma tolerance to Ni may also have contributed to the lack of response to increased Ni in heterospecific pollen. This study paves the way for additional tests in other metal hyperaccumulators and recipients, and to identify mechanisms of interactions on the stigma.


Effect of age on auditory evoked responses (AER) and augmenting-reducing.
Auditory evoked responses (AER) were obtained from Cz and Fz in 30 adults (14 male, 16 female) from 20-80 years old. Sound bursts (1000 Hz-200 msec) of four different intensities were used. Peak to trough amplitudes of P1N1 and N1P2 and latencies of P1, N1 and P2 peaks were measured with increasing stimulus intensity and slopes of amplitude - intensity and latency - intensity curves were analysed for assessment of an age effect. The main result is that the increase in P1N1 amplitude with increasing stimulus intensity is more pronounced in older persons. Previous studies have established a negative correlation between the augmenting-reducing responses and HVA levels in the CSF (with lower amounts of HVA in the CSF of "augmenters"). Decreased dopamine metabolism in old subjects could account for our results, so further studies should focus on patients with pathological dopamine deficiencies.


A Green Media Access Method for IEEE 802.15.6 Wireless Body Area Network.
It is of utmost importance to conserve battery energy to the maximum possible extent in WBAN nodes while collecting and transferring medical data. The IEEE 802.15.6 WBAN standard does not specify any method to conserve energy. This paper focuses on a method to conserve energy in IEEE 802.15.6 WBAN nodes when using CSMA/CA, while simultaneously restricting data delivery delay to the required value as specified in medical applications. The technique is to allow the nodes to sleep all the times except for receiving beacons and for transmitting data frames whenever a data frame enters an empty buffer. The energy consumed by the nodes and the average latency of data frame for periodical arrival of data are found out analytically. The analytical results are validated and also the proposed method is compared with other energy conserving schemes, using Castalia simulation studies. The proposed method shows superior performance in both device lifetime and latency of emergency medical data.


Expanding the boundaries of atomic spectroscopy at the single-cell level: critical review of SP-ICP-MS, LIBS and LA-ICP-MS advances for the elemental analysis of tissues and single cells.
Metals have a fundamental role in microbiology, and accurate methods are needed for their identification and quantification. The inability to assess cellular heterogeneity is considered an impediment to the successful treatment of different diseases. Unlike bulk approaches, single-cell analysis allows elemental heterogeneity across genetically identical populations to be related to specific biological events and to the effectiveness of drugs. Single particle-inductively coupled plasma-mass spectrometry (SP-ICP-MS) can analyse single cells in suspension and measure this heterogeneity. Here we explore advances in instrumental design, compare mass analysers and discuss key parameters requiring optimisation. This review has identified that the effect of pre-treatment of cell suspensions and cell fixation approaches require further study and novel validation methods are needed as using bulk measurements is unsatisfactory. SP-ICP-MS has the advantage that a large number of cells can be analysed; however, it does not provide spatial information. Techniques based on laser ablation (LA) enable elemental mapping at the single-cell level, such as laser-induced breakdown spectroscopy (LIBS) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). The sensitivity of commercial LIBS instruments restricts its use for sub-tissue applications; however, the capacity to analyse endogenous bulk components paired with developments in nano-LIBS technology shows great potential for cellular research. LA-ICP-MS offers high sensitivity for the direct analysis of single cells, but standardisation requires further development. The hyphenation of these trace elemental analysis techniques and their coupling with multi-omic technologies for single-cell analysis have enormous potential in answering fundamental biological questions.


Advancement of cloud-based accounting effectiveness, decision-making quality, and firm performance through digital transformation and digital leadership: Empirical evidence from Vietnam.
The accounting literature is silent about how digital transformation can be transformed into outstanding business performance through cloud-based accounting effectiveness (CBAE) under the supervision of digital leaders. In the digital age, this mechanism is practically significant for emerging market firms to promote accounting practices and decision-making effectiveness. Thus, this study investigates how CBAE and decision-making quality (DMQ) mediate the impact of digital transformation on firm performance. In addition, the moderating effects of digital leadership on the relationships between digital transformation and CBAE and those between CBAE and DMQ are investigated. The proposed model and its hypotheses are evaluated using partial least squares structural equation modeling (PLS-SEM) on survey data from 252 large-sized Vietnamese firms. The study's findings are as follows: (1) digital transformation positively affects CBAE, which affects DMQ and firm performance; (2) when digital leadership is strong, the effects of digital transformation on CBAE and CBAE on DMQ are amplified. These findings demonstrate how the interaction between digital transformation and digital leadership can contribute to the success of firms in emerging markets that use cloud accounting. In addition, the current study elucidates the mechanism by which digital transformation influences the digitalization of accounting practices and contributes to our understanding of digital transformation research in accounting by introducing digital leadership as a boundary condition.


People with visual impairment in outward-facing work: Developing a tool to measure employer attitudes.
Over the years, persons with disabilities have suffered unjustifiably due to a low employment rate, largely the result of unsupportive and negative attitude from employers. Such attitudes are exacerbated during periods of economic stress, with a case par excellence being the current COVID-19 pandemic. Prior studies have addressed common concerns of employers within the workplace. However, the dimensions of these concerns extend beyond the internal working environment, to the outward-facing work environment, involving interactions with customers and suppliers. These concerns have not, thus far, been properly addressed. To develop the Service from People With Visual Impairment (SPVI) psychometric measure, a 6-item employers' attitude assessment tool. This study is based on 1,036 questionnaires collected using Online Panel Data (OPD), from managers who have hiring authority. We performed Exploratory Factor Analysis (EFA) followed by Confirmatory Factor Analysis (CFA) for discriminant and convergent validity. Finally, we present an empirical model comprising a stable single factor and establish predictive validity using Structural Equation Modeling (SEM). CFA showed good fit to the observed data; CMIN/DF = 1.94, p > 0.05, CFI = 1, TLI = 0.99, NFI = 1, RMSEA = 0.03. SEM showed good fit; CMIN/DF = 1.91, CFI = 1, TLI = 0.99, NFI = 0.99, RMSEA = 0.03. The results suggest that the instrument could become a pragmatic tool to assess employer attitudes to employ people with visual impairment or blindness due to external work environment concerns. The tool is relevant to a wide range of circumstances, including economic downturns. Practical considerations are discussed.


Imaging of aromatase distribution in rat and rhesus monkey brains with [11C]vorozole.
Aromatase is an enzyme that converts androgens to estrogens and may play a role in mood and mental status. The aim of this study was to demonstrate that brain aromatase distribution could be evaluated with a novel positron emission tomography (PET) tracer [(11)C]vorozole. Vorozole is a nonsteroidal aromatase inhibitor that reversibly binds to the heme domain of aromatase. In vitro experiments in rat brain, using frozen section autoradiography, illustrated specific binding in the medial amygdala (MA), the bed nucleus of stria terminalis (BST) and the preoptic area (POA) of male rat brain. Specific binding in female rat brain was found in the MA and the BST; however, the signals were lower than those of males. The K(d) of [(11)C]vorozole binding to aromatase in MA was determined to be 0.60+/-0.06 nM by Scatchard plot analysis using homogenates. An in vivo PET study in female rhesus monkey brain demonstrated the uptake of [(11)C]vorozole in the amygdala, where the uptake was blocked by the presence of excess amounts of unlabeled vorozole. Thus, this tracer has a high affinity for brain aromatase and could have a potential for in vivo aromatase imaging. This technique might enable the investigation of human brain aromatase in healthy and diseased persons.


Giant cell arteritis incidence: analysis by season and year in mid-Atlantic United States.
Evaluate the incidence of biopsy-proven giant cell arteritis for seasonal or annual variability in the Mid-Atlantic United States. Retrospective chart review of all patients undergoing temporal artery biopsy from 1994 to 2011. The charts of 744 patients were reviewed, and 215 patients were diagnosed with giant cell arteritis based on positive temporal artery biopsy results. All results between 1994 and 2011 were reviewed. Giant cell arteritis incidence data were evaluated by year, season and month for any trends or cyclic patterns. Incidence of biopsy-proven giant cell arteritis. The majority of patients were female (74%) and over the age of 60 (98.6%). The diagnosis of biopsy-proven giant cell arteritis was found in 215 of 744 (28.9%) patients. The incidence of biopsy-proven giant cell arteritis by year varied, with the peak incidence in 1996. The monthly incidence peaked in July and had a trough in October. However, Poisson regression analysis did not show any statistically significant trend over time or cyclic pattern to the incidence by year, season or month. The incidence of biopsy-proven giant cell arteritis in the population studied did not have any significant cyclic pattern over the last 17 years. The highest incidence by month was noted in July with a trough in October. However, this was not a significant pattern by month or season to support infectious or periodic environmental factors inciting giant cell arteritis.


Evaluation of the chronic antianginal effect of molsidomine.
The activity of molsidomine, a new antianginal drug, was investigated in 33 patients treated for 3 months with doses of 2 mg, three or four times daily. Exertional angina was present before treatment in 16 patients, spontaneous angina in 5, and mixed angina in twelve. Thirty patients completed the study, and three retired because of side effects. A reduction in the number of attacks of more than 75% in comparison to the pretreatment period was obtained in 20 cases, a diminution between 50% and 75% in 6, and a reduction below 50% in 6. Satisfactory increases in the duration (from 6 minutes 25 seconds to 11 minutes 40 seconds) and maximum load (89.6 to 139.3 W) were obtained in 80% of the cases of effort angina. A dramatic and statistically significant reduction of attacks was observed in the first 48 hours in 8 of 11 patients with spontaneous angina. Side effects were predominantly gastrointestinal and caused the interruption of treatment in 10% of the cases. Molsidomine seems to be a very promising drug for the treatment of effort and spontaneous angina.


EOS-3D-DCNN: Ebola optimization search-based 3D-dense convolutional neural network for corn leaf disease prediction.
Corn disease prediction is an essential part of agricultural productivity. This paper presents a novel 3D-dense convolutional neural network (3D-DCNN) optimized using the Ebola optimization search (EOS) algorithm to predict corn disease targeting the increased prediction accuracy than the conventional AI methods. Since the dataset samples are generally insufficient, the paper uses some preliminary pre-processing approaches to increase the sample set and improve the samples for corn disease. The Ebola optimization search (EOS) technique is used to reduce the classification errors of the 3D-CNN approach. As an outcome, the corn disease is predicted and classified accurately and more effectually. The accuracy of the proposed 3D-DCNN-EOS model is improved, and some necessary baseline tests are performed to project the efficacy of the anticipated model. The simulation is performed in the MATLAB 2020a environment, and the outcomes specify the significance of the proposed model over other approaches. The feature representation of the input data is learned effectually to trigger the model's performance. When the proposed method is compared to other existing techniques, it outperforms them in terms of precision, the area under receiver operating characteristics (AUC), f1 score, Kappa statistic error (KSE), accuracy, root mean square error value (RMSE), and recall.


Allopurinol adherence and its predictors in gout: a national cohort study in US veterans.
Allopurinol is a frequently used, effective, and affordable medication for gout. However, poor adherence to allopurinol is a key reason for patients not reaching treatment goals. The aim of this study was to comprehensively assess factors associated with high allopurinol adherence in gout. In this national cohort study, we used the health-care databases of the US Department of Veterans Affairs (VA) from 2002 to 2016 and a new-user design to assess potential predicting factors of allopurinol adherence. Veterans were included in this study if they had International Classification of Diseases (ninth revision) code 274.x for gout in two or more outpatient encounters or one or more inpatient encounters during 2002-16; incident allopurinol use; and at least 12 months of observation. Potential predictors of allopurinol adherence (defined as medication possession ratio [days used divided by days prescribed] of >80%) were examined using Andersen's health-care utilisation model and multivariable-adjusted logistic regression analyses. Between Oct 1, 2002, and Sept 30, 2016, 565 812 potentially eligible patients were included in the VA database, of whom 264 614 (46·8%) met the eligibility criteria and were included in the study cohort. The mean age was 67·8 years (SD 11·7) and mean body-mass index was 33·0 kg/m2 (6·4). Factors significantly associated with higher odds of allopurinol adherence in multivariable-adjusted analyses were older age (odds ratio 1·01, 95% CI 1·01-1·01); Deyo-Charlson comorbidity index score of 1 (1·05, 1·02-1·07) or 2 or more (1·05, 1·03-1·07) versus a score of 0; higher body-mass index (all categories from 25 to <30 [1·12, 1·08-1·17] to ≥45 [1·47, 1·39-1·55] vs 18·5 to <25); a military service connection of 50% or higher (1·37, 1·29-1·46) versus 0%; care in a community-based outpatient clinic (1·11, 1·08-1·14) versus in a VA Medical Center; and rural residence (1·02, 1·00-1·05). Factors significantly associated with lower odds of allopurinol adherence were black (0·74, 0·72-0·76), Hispanic (0·68, 0·65-0·72), or other race or ethnicity (0·86, 0·82-0·89) versus white race; non-rheumatologist care provider (0·83, 0·79-0·88); allopurinol start dose of 101-200 mg per day (0·93, 0·91-0·95) or more than 300 mg per day (0·75, 0·72-0·79) versus 100 mg per day or less; or allopurinol use in the previous year (0·80, 0·79-0·82). Compared with residence in the Midwest, patients in other US regions had lower odds of adherence (mid-Atlantic 0·89, 0·87-0·92; northeast 0·84, 0·81-0·87; south 0·85, 0·83-0·88; west 0·86, 0·83-0·89). Compared with a baseline serum urate of 360 to less than 480 μmol/L, serum urate of less than 360 μmol/L was associated with higher odds of adherence (1·28, 1·25-1·32), whereas baseline serum urate of 480 to less than 600 μmol/L (0·86, 0·84-0·88) or 600 to less than 720 μmol/L (0·92, 0·89-0·94) was associated with lower odds of adherence. We identified several important factors associated with high allopurinol adherence. Clinicians and policy makers can now target modifiable factors at the patient, provider, or systems level, with the aim of improving allopurinol adherence, and thereby overall gout care.


Covert orienting of attention and overt eye movements activate identical brain regions.
This study investigated the anatomical relationship between covert and overt shifts of attention. Previous studies have found that the areas of the brain activated by covert and overt shifts of attention are very similar. However, despite a general agreement between studies there are a few issues that merit closer inspection. Primarily, the tasks aiming to produce covert or overt shifts of attention were not always comparable. Secondly, the previous studies disagreed on whether greater neural activity is elicited by covert shifts or overt shifts of attention. Thirdly, the previous studies differed on whether the shifts of attention were exogenously or endogenously driven. Finally, the statistical analyses used by all previous studies failed to account for between subject variability. The present study was designed to address all these issues. Twelve healthy subjects performed either covert or overt shifts of attention while the functional magnetic resonance imaging (fMRI) signal was continuously measured. In line with the previous studies, the present study showed a virtually complete overlap between areas of the brain recruited during covert shifts of attention and areas of the brain recruited during overt shifts of attention. Furthermore, using endogenously driven shifts of attention this study found that overt shifts of attention resulted in higher levels of activation in the brain than covert shifts of attention. The results of this study provide support for the premotor theory of attention that posits that the attentional and motor systems are the result of neural activation in the same areas of the brain.


Biomechanical properties of fixed-angle volar distal radius plates under dynamic loading.
To evaluate and compare the biomechanical properties of 8 different locked fixed-angle volar distal radius plates under conditions designed to reflect forces seen in early fracture healing and postoperative rehabilitation. We evaluated the Acumed Acu-Loc (Acumed, Hillsboro, OR), Hand Innovations DVR (Hand Innovations, Miami, FL), SBi SCS volar distal radial plate (Small Bone Innovations, Morrisville, PA), Synthes volar distal radius plate and EA extra-articular volar distal radius plate (Synthes, Paoli, PA), Stryker Matrix-SmartLock (Stryker Leibinger, Kalamazoo, MI), Wright Medical Technology Locon VLS (Wright Medical Technology, Arlington, TN), and Zimmer periarticular distal radius locking plate (Zimmer, Warsaw, IN). After affixing each plate to a synthetic corticocancellous radius, we created a standardized dorsal wedge osteotomy. Each construct had cyclic loading of 100 N, 200 N, and 300 N for a total of 6000 cycles. Outcomes, including load deformation curves, displacement, and ultimate yield strengths, were collected for each construct. The Wright plate was significantly stiffer at the 100 N load than the Zimmer plate and was stiffer at the 300 N load than 4 other plates. The Zimmer and Hand Innovations plates had the highest yield strengths and significantly higher yield strengths than the Wright, SBi, Stryker, and Synthes EA plates. Given the biomechanical properties of the plates tested, in light of the loads transmitted across the native wrist, all plate constructs met the anticipated demands. It seems clear that fracture configuration, screw placement, cost, and surgeon familiarity with instrumentation should take priority in selecting a plating system for distal radius fracture treatment. This study provides further information to surgeons regarding the relative strengths of different plate options for the treatment of distal radius fractures.


Hallmarks of Comparative Transcriptome between Rhizomorphs and Hyphae of Armillaria sp. 541 Participating in Fungal Symbiosis with Emphasis on LysM Domains.
Armillaria sp. 541, a genus of root-infecting fungi, forms a symbiosis with traditional Chinese medicine Gastrodia elata (Orchid) and Polyporus umbellatus via extensive networks of durable rhizomorphs. It is not clear the hallmarks of comparative transcriptome between the rhizomorphs and hyphae of Armillaria sp. 541. In the present study, transcriptomic analysis of Armillaria sp. 541 identified 475 differentially expressed genes (DEGs) between Armillaria rhizomorphs (AR) and hyphae (AH). Of them, 285 genes were upregulated and 190 were downregulated. Bioinformatics analyses and tests demonstrated DEGs involved in oxidoreductase activity and peptidoglycan binding were significantly enriched in this process when rhizomorph formed from hyphae. We accordingly obtained 14 gene-encoding proteins containing the LysM domain, and further consensus pattern and phylogenetic analysis indicated that their amino acid sequences were conserved and their biological functions may be peptidoglycan binding for recognition between the fungus and host. Among these genes, one, named Armillaria LysM domain recognition gene (aLDRG), was expressed significantly when rhizomorphs were differentiated from hyphae. It was located in the cortical cells of the rhizomorph by in situ hybridization. Furthermore, biolayer interferometry (BLI) assay demonstrated that aLDRG can bind specifically to chitin oligosaccharide of the fungal cell wall, including N,N',N″-Triacetylchitotriose (CO3) and N,N',N″,N'″,N″″-Pentaacetylchitopentaose (CO5). Therefore, we deduced that Armillaria sp. 541 expressed higher levels of LysM protein aLDRG for better binding of oligosaccharide after rhizomorphs were generated. This study provides functional genes for further studies on the interaction between Armillaria sp. 541 and its host.


Serotype-selective, small-molecule inhibitors of the zinc endopeptidase of botulinum neurotoxin serotype A.
Botulinum neurotoxin serotype A (BoNTA) is one of the most toxic substances known. Currently, there is no antidote to BoNTA. Small molecules identified from high-throughput screening reportedly inhibit the endopeptidase--the zinc-bound, catalytic domain of BoNTA--at a drug concentration of 20 microM. However, optimization of these inhibitors is hampered by challenges including the computational evaluation of the ability of a zinc ligand to compete for coordination with nearby residues in the active site of BoNTA. No improved inhibitor of the endopeptidase has been reported. This article reports the development of a serotype-selective, small-molecule inhibitor of BoNTA with a K(i) of 12 microM. This inhibitor was designed to coordinate the zinc ion embedded in the active site of the enzyme for affinity and to interact with a species-specific residue in the active site for selectivity. It is the most potent small-molecule inhibitor of BoNTA reported to date. The results suggest that multiple molecular dynamics simulations using the cationic dummy atom approach are useful to structure-based design of zinc protease inhibitors.


Acyl CoA:retinol acyltransferase (ARAT) activity is present in bovine retinal pigment epithelium.
Visual perception is mediated by a family of G protein-coupled receptors called the opsins. The light-absorbing chromophore in most opsins is 11-cis-retinaldehyde, which is isomerized to all-trans-retinaldehyde upon absorption of a photon. Restoration of light sensitivity to the photobleached opsin requires chemical re-isomerization of the chromophore. This is carried out by an enzymatic pathway called the visual cycle in retinal pigment epithelial cells. The isomerase in this pathway uses fatty-acyl esters of all-trans-retinol as substrate. A retinyl-ester synthase that produces these esters, called lecithin:retinol acyltransferase (LRAT), has been extensively characterized. Based on prior biochemical studies and the phenotype in lrat(-/-) knockout mice, it has been assumed that LRAT is the sole or dominant retinyl-ester synthase in the retinal pigment epithelium. Here we demonstrate the presence of a second ester synthase activity in these cells called acyl CoA:retinol acyltransferase (ARAT). We show that this activity uses palmitoyl coenzyme A as an acyl donor, unlike LRAT which uses phosphatidylcholine. Similar to LRAT, ARAT esterifies both all-trans-retinol and 11-cis-retinol. LRAT and ARAT are both potently inhibited by the retinyl-ester analog, all-trans-retinylbromoacetate, but only ARAT is inhibited by progesterone. Unexpectedly, the maximum turnover rate (V(max)) of ARAT was similar to that of LRAT. However, the Michaelis constant (K(M)) of ARAT was 10-fold higher than the K(M) of LRAT for all-trans-retinol. These observations suggest that ARAT may complement LRAT to provide additional retinyl-ester synthase activity under conditions of high all-trans-retinol. These conditions occur in the retina following exposure to bright light.


[Soft tissue balanced navigation of total knee arthroplasties].
Implantation of a total knee arthroplasty with a correct mechanical axis, a rectangular joint gap and a reconstructed joint line by use of an imageless computer navigation device Symptomatic gonarthrosis if non operative treatment or joint preserving operations remains ineffective Infections; soft tissue damage in the approach area; massive instability of the collateral ligaments Medial parapatellar approach to the knee joint; diminution of the patella; fixation of the reference arrays in tibia and femur; registration of leg axis, ligament balance and surface of the knee joint by use of the navigation system; tibial resection perpendicular to the mechanical axis; ligament balancing to achieve a rectangular extension gap; femoral implant planning to maintain the original joint line and reconstruct an equal joint gap in extension and flexion; femora resection perpendicular to the mechanical axis; reconstruction of the rectangular flexion gap by rotation of the femoral resection; two stage cementing technique for fixation of the original implants; check of the final mechanical axis and symmetry of the joint gap over the whole range of motion; wound closure. Physiotherapy; continuous passive motion treatment; mobilization with 20 kg weight bearing with 2 crutches for 2 weeks, thereafter with 2 crutches and incremental full weight bearing for 4 weeks. The analysis of 582 consecutive navigated total knee arthroplasties showed one case of extension gap instability > 3 mm (0.2%) and 8 patients with flexion gap instability > 3 mm (1.4%). A too tight flexion gap was registered in 23 patients (4.4%), a too wide flexion gap in 13 cases (2.5%). The joint line was reconstructed with an average inaccuracy of 0 mm, in 17 patients the joint line was elevated > 3 mm (2.9%).


Aliskiren attenuates myocardial apoptosis and oxidative stress in chronic murine model of cardiomyopathy.
Doxorubicin (DXR) is one of the most effective antineoplastic agents. However, the optimal clinical use of this agent is limited because of marked cardiomyopathy and congestive heart failure. Renin angiotensin system (RAS) plays an important role in the development of cardiac hypertrophy, reperfusion injury and congestive heart failure. Aliskiren (ALK) is a direct inhibitor of renin and does not affect other systems involved in cardiovascular regulation. This study was designed to explore the possible protective effects of ALK (30 and 100 mg/kg, per oral [p.o.] respectively for 42 days) in chronic model of DXR (1.25 mg/kg, intraperitoneally (i.p.) sixteen equal cumulative doses) induced cardiomyopathy in rats. DXR treatment significantly (P<0.01) increased the activities of serum creatine kinase (CK-MB), lactate dehydrogenase (LDH), cardiomyocyte caspase-3 and catalase (CAT). ALK (100 mg/kg) treatment prevented the animals significantly (P<0.01) from rise in the above indices. Furthermore ALK (100 mg/kg) significantly restores the DXR-induced decrease in antioxidant defense, reduced glutathione (GSH) and superoxide dismutase (SOD). Transmission electron microscopic studies showed that DXR caused apoptosis in myocardium, manifested as condensation of chromatin network at the margins and rupture of nuclear membrane which was well protected by ALK (100 mg/kg) treatment. The present study indicates that ALK protected rats from DXR-induced cardiomyopathy.


Effect of desogestrel-containing oral contraceptives on vascular reactivity and catecholamine levels.
The modifications induced by new oral contraceptives (OC) on blood pressure, great vessel vascular reactivity by color Doppler, and catecholamine levels were investigated. Young healthy women not taking OC (n = 22; controls) or receiving, for > or = 6 months, OC containing desogestrel with either 30 micrograms (n = 14) or 20 micrograms of EE (n = 8) were enrolled. Blood pressure measured at rest in supine position was similar between controls and OC users. The pulsatility index (PI), an indirect index of resistance to blood flow, of axillary artery was significantly higher (p < 0.05) in 30 micrograms than in 20 micrograms EE OC users or controls. A similar trend, albeit not significant, was observed for the internal carotid artery PI. Norepinephrine (p < 0.01) and dopamine (p < 0.05) but not epinephrine levels, were lower in 30 micrograms EE OC users than in 20 micrograms EE OC users or controls. Thus, both 20 micrograms and 30 micrograms EE OC had no negative effect on blood pressure, but the 30 micrograms EE OC tended to increase great vessel resistance to blood flow, independently of catecholamine levels.


Variability of polymorphic families of three types of xylanase inhibitors in the wheat grain proteome.
Cereals contain proteinaceous inhibitors of endo-beta-1,4-xylanases (E.C.22.214.171.124, xylanases). Since these xylanase inhibitors (XIs) are only active against xylanases of microbial origin and do not interact with plant endogenous xylanases, they are believed to act as a defensive barrier against phytopathogenic attack. So far, three types of XIs have been identified, i.e. Triticum aestivum XI (TAXI), xylanase inhibiting protein (XIP), and thaumatin-like XI (TLXI) proteins. In this study the variation in XI forms present in wheat grain was elucidated using high-resolution 2-DE in combination with LC-ESI-MS/MS and biochemical techniques. Reproducible 2-DE fingerprints of TAXI-, XIP-, and TLXI-type XIs, selectively purified from whole meal of three European wheat cultivars using cation exchange chromatography followed by affinity chromatography, were obtained using a pH-gradient of 6 to 11 and a molecular mass range of 10 to 60 kDa. Large polymorphic XI families, not known to date, which exhibit different pI- and/or molecular mass values, were visualised by colloidal CBB staining. Identification of distinct genetic variants by MS/MS-analysis provides a partial explanation for the observed XI heterogeneity. Besides genetic diversity, PTMs, such as glycosylation, account for the additional complexity of the 2-DE patterns.


Single/co-adsorption and mechanism of methylene blue and lead by β-cyclodextrin modified magnetic alginate/biochar.
Due to the high biological toxicity, the concurrent elimination of lead (Pb (II)) and methylene blue (MB) has become a challenging problem. Therefore, a newly β-cyclodextrin (β-CD) modified magnetic alginate/biochar (β-CD@MBCP) material was developed. Comprehensive characterizations proved the successful coating of β-CD onto MBCP surface by microwave-aided fabrication. The β-CD@MBCP achieved high-efficiency uptake for contaminants under a wide pH scope. In the dual system, Pb (II) elimination was facilitated with the presence of MB, due to the active sites provided by MB. In the presence of Pb (II), MB uptake was inhibited due to the electrostatic repulsion between positively charged MB and Pb (II). Electrostatic attraction and complexation contributed to capturing Pb (II), while π-π interactions, host-guest effect, and H-bonding were important in MB elimination. After four cycles, β-CD@MBCP maintained comparatively good renewability. Findings demonstrated that β-CD@MBCP could be an effective remediation material for Pb (II)/MB adsorption from aqueous environments.


Microarray analysis of changes in gene expression in a murine model of chronic chagasic cardiomyopathy.
Chagas' disease, caused by infection with Trypanosoma cruzi, is a major cause of cardiomyopathy in endemic regions. Infection leads to cardiac remodeling associated with congestive heart failure and dilated cardiomyopathy. In order to study the changes in the gene expression profile due to infection, C57BL/6 x 129sv male mice were infected with 1 x 10(3) trypomastigotes of the Brazil strain of T. cruzi. Histopathological examination of the myocardium revealed chronic inflammation, vasculitis and fibrosis 100 days post-infection. Cardiac magnetic resonance imaging revealed a significantly dilated heart compared with uninfected mice. The relative abundance or depletion of myocardial mRNAs was evaluated using high-density microarrays consisting of 27,400 mouse cDNAs, which were hybridized with fluorescent probes generated from mRNAs of T. cruzi infected and uninfected hearts. Differentially expressed genes were sorted according to their normalized expression patterns and functional groups including those involved in transcription, intracellular transport, structure/junction/adhesion or extracellular matrix, signaling, host defense, energetics, metabolism, cell shape and death. The regulated genes are interpreted in the pathogenesis of chagasic heart disease.


In vitro assessment of stainless steel orthodontic brackets coated with titanium oxide mixed Ag for anti-adherent and antibacterial properties against Streptococcus mutans and Porphyromonas gingivalis.
Orthodontic brackets made from stainless steel were introduced in dentistry, though they have less ability in reducing enamel demineralization and are not successful in preventing microbial as well as biofilm growth. In this study, we evaluated the significant role of different brackets in reducing enamel demineralization indirectly. Results from different tests indicate the significant reduction in adhesion, biofilm formation and slow growth of tested bacterial species on brackets coated with Ag + TiO2 and found to be statistically significant lower than control. There was no loss in cell viability in all brackets indicating that the cells are biocompatible with different bracket materials. Scanning electron microscopy showed less bacteria attached with the surface coated with Ag + TiO2 indicated that bacteria were losing adherent nature on coated surface. In conclusion, TiO2+Ag coating on stainless steel brackets possessed anti-adherent properties and also have demonstrable antibacterial properties therefore helps in preventing dental caries and plaque accumulation indirectly. The cell compatibility of TiO2+Ag coated brackets is superior to the uncoated samples therefore can be used in orthodontics as it not only provide suitable antimicrobial activity and resistance to biofilm formation but also sustained the cell viability of human gingival fibroblast (HGF) cell lines.


An incision for extended suprahilar retroperitoneal lymphadenectomy.
To fulfill the necessary criteria for adequate exposure for extended suprahilar retroperitoneal lymphadenectomy we have used a thoracoabdominal midline extraperitoneal incision that affords the high exposure of a thoracoabdominal incision without sacrificing the broad exposure afforded by a midline incision and maintains the advantages of the extraperitoneal approach.


Octogenarian free flap reconstruction: complications and cost of therapy.
The study goal was to document the reliability, incidence of complications, and cost of therapy for patients older than 80 years who undergo microvascular head and neck reconstruction. Thirteen octogenarians underwent free flap reconstruction of defects resulting from the treatment of head and neck cancer at an academic tertiary care medical center. The incidence of medical and reconstructive complications and the cost of hospitalization were compared with those for 99 younger patients who were treated during the same time period. There were no cases of free flap failure or significant reconstructive complications in the octogenarians. The incidence of medical complications was 62% in the octogenarians and 15% in the younger patients. The average cost of therapy was $54,702 per octogenarian patient compared with $30,397 per younger patient. The increased incidence of medical complications and increased cost arose primarily from an increased severity of preoperative systemic illness in the octogenarians. However, controlling for comorbidity did not eliminate the discrepancy in medical complications between the octogenarians and the younger patients. Although microvascular head and neck reconstruction in the elderly is very reliable, the incidence of medical complications and the cost of therapy are significantly increased in octogenarians.


Generalized convulsive status epilepticus in Creutzfeldt-Jakob disease.
We report a patient who was referred to our department because of generalized status epilepticus. His condition deteriorated rapidly and he died 1 month after admission. Autopsy confirmed the clinical diagnosis of Creutzfeldt-Jakob disease (CJD). CJD should be added to the list of rare but possible causes of generalized status epilepticus.


Immunohistochemical investigations in epidermal Merkel cells--a common phenotype with eccrine sweat gland epithelium.
Mono- and polyclonal antibodies were used for immunofluorescence investigations in cytoskeletal and associated antigens on frozen sections of adult human skin. Epidermal Merkel cells were identified in the stratum basale. Their phenotype was compared with other epithelial cells of human skin. The inner duct epithelium of eccrine sweat glands showed an immunoreactivity similar to that of epidermal Merkel cells. A common origin of both cell types is suggested.


[Economic aspects of prevention. Efficiency and structure of the health care system].
The structure of the health care system has been examined, the health care sector being defined as all measures taken to promote and preserve good health. A review of the international literature came to the following conclusions:--The correlation between medical care and health status is at most very limited.--The empirical evidence suggests that efficient preventive programs--both for primary and for secondary prevention--would be possible.--We therefore come to the conclusion that the division between medical care and prevention is not optimal and that furthering prevention at the cost of medical care would increase the efficiency of the health care sector. Conclusive statements concerning the efficiency of additional preventive measures are not possible with the research undertaken to date.


Enhancement of copper resistance and CupI amplification in carcinogen-treated yeast cells.
Carcinogen-induced amplification at the CupI locus, coding for a metallothionein protein, was studied in the yeast Saccharomyces cerevisiae. Exposure of cells from three different haploid strains, 4939, DBY746 and 320, to chemical carcinogens such as N-methyl-N'-nitro-N-nitroso-guanidine (MNNG), ethylmethanesulfonate (EMS) and 4-nitroquinoline-N-oxide (4NQO) enhanced the frequency of copper-resistant colonies up to several hundred fold. Copper-resistant clones obtained from strains DBY746 and 320, which contain more than one copy of the CupI locus, displayed a four- to eightfold amplification of the CupI sequences. In these clones the amplified CupI sequences were organized in a tandem array. Carcinogen treatment of strain 4939 in which only one copy of the CupI gene is present produced resistant colonies without CupI amplification. The possible use of the yeast system to study gene duplication and amplification is discussed.


Magnetic resonance angiography in moyamoya disease.
Spontaneous occlusion of the circle of Willis, i.e., moyamoya disease (MMD), is a clinical disease entity angiographically characterized by progressive and bilateral stenosis of the carotid bifurcation, with a hazy collateral network at the base or convexity of the brain. Although the importance of computed tomography (CT) and conventional magnetic resonance (MR) imaging in diagnosing MMD has already been determined, conventional arteriography is still regarded as necessary for definitive diagnosis. Magnetic resonance angiography (MR-A) is a very recent vascular imaging technique which allows noninvasive and direct imaging of vessels without the use of contrast medium. We present four pediatric cases of MMD, evaluated by conventional angiography, CT, MR imaging, and MR-A. Our data demonstrate that MR-A is successful both in allowing detection of occlusive disease of the basal portion of the internal carotid artery and large branch basal cerebral vessels and demonstrating the collateral vessels at the base of the brain. As a noninvasive procedure, MR-A promises to become a valuable alternative to classical angiography in the diagnosis of MMD.


Cardiac perforation by a guide wire during subclavian catheter insertion.
We report a patient in whom cardiac perforation was directly caused by a straight soft tipped guide wire used to introduce a subclavian dialysis catheter. We recommend the use of J tip guide wires to avoid this life threatening complication.


A follow-up study of platelet-rich plasma serotonin in clinical subtypes of cerebral infarction.
The serotonin concentration in the platelet-rich plasma of 32 patients with single and multiple stroke type cerebral infarction was investigated at various stages. Serotonin levels were decreased in the acute period. The incidence of serotonin abnormality was higher in multiple types than in the single type. Serotonin levels were significantly decreased in treated hypertensive patients compared with untreated patients. Serotonin levels, therefore, varied according to the type and stage of cerebral infarction.


Optic neuritis with positive HLA-B27: Characteristic phenotype in the Chinese population.
This study retrospectively reviewed the clinical features of optic neuritis (ON) with positive HLA-B27. Clinical data were reviewed for HLA-B27-positive ON in the Chinese People's Liberation Army General Hospital from January 2009 through June 2015. The prevalence of HLA-B27 and spondyloarthropathies was analyzed. Clinical features of HLA-B27-positive ON based on serum aquaporin 4-antibody (AQP4-Ab) were compared. A total of 22 ON patients (14 female/8 male, 38 involved eyes) with positive HLA-B27 were collected from 410 ON patients. Recurrent episodes were observed in 14/22 patients, and seven patients presented as bilateral simultaneous ON. A total of 68.4% (22/38) of involved eyes exhibited severe visual impairment (<0.1) at onset. A total of 8/22 patients were seropositive for AQP4-Ab, and clinical features did not differ based on AQP4-Ab status. Bilateral sacroiliitis was revealed in over 50% (7/13) of patients screened using pelvic computed tomography. Three patients were diagnosed with ankylosing spondylitis (AS), and one patient experienced co-occurrence of active AS and bilateral ON. HLA-B27-positive ON may presented recurrent episodes and severe visual impairment at onset. The co-occurrence of ON and AS, and the frequent presence of bilateral sacroiliitis may indicate an underlying alternation of autoimmune background in this condition.


2,6-Di-bromo-4-methyl-aniline.
In the title compound, C7H7Br2N, the C-C-C bond angles of the benzene ring are notably distorted and two short intamolecular N-H⋯Br contacts occur. In the crystal, the mol-ecules are linked by N-H⋯N hydrogen bonds to generate C(2) chains propagating in the [100] direction.


Hepatitis B vaccination among 1997-2011 birth cohorts in rural China: the potential for further catch-up vaccination and factors associated with infant coverage rates.
Hepatitis B vaccination rates in China have recently increased. This study aimed to investigate infant vaccination coverage for birth cohorts from 1997 to 2011 in rural regions and to assess catch-up vaccination potential. We used questionnaire-based interviews from a cross-section of 6,529 individuals from seven provinces. Logistic regression analyses were used to model two measures of infant vaccination status, namely, birth dose within 24 hours and three doses within the first year of life. During interviews, individuals' vaccination status and vaccination plan were recorded. Unvaccinated individuals without plans for future vaccination were presented with a hypothetical offer of free vaccination and indirect cost compensation. Institutional birth rates were higher than vaccination rates, but both increased over time. Vaccination coverage rates were not significantly associated with sex. Infant vaccination coverage was positively associated with a mother's educational level, household income level, knowledge of transmission routes, and perceived duration of protection obtained through vaccination. Vaccination status at the time of the survey showed the occurrence of catch-up vaccinations, but a notable percentage of individuals remained unvaccinated and had no plans for future vaccination. Of these individuals, approximately 50% were prepared to accept vaccination if offered free of charge.


SARS-CoV-2 detection by fluorescence loop-mediated isothermal amplification with and without RNA extraction.
Rapid and simple point-of-care detection of SARS-CoV-2 is an urgent need to prevent pandemic. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) can detect SARS-CoV-2 more rapidly than RT-PCR. Saliva is non-invasive specimen suitable for mass-screening, but data comparing utility of nasopharyngeal swab (NPS) and saliva in RT-LAMP test are lacking and it remains unclear whether SARS-CoV-2 could be detected by direct processing of samples without the need for prior RNA extraction saliva. In this study, we compared utility of saliva and NPS samples for the detection of SARS-CoV-2 by a novel RT-fluorescence LAMP (RT-fLAMP). The sensitivity and specificity of the RT-fLAMP with RNA extraction were 97% and 100%, respectively, with equivalent utility of NPS and saliva. However, sensitivity was decreased to 71% and 47% in NPS and saliva samples without RNA extraction, respectively, suggesting that RNA extraction process may be critical for the virus detection by RT-fLAMP.


Computer model of cardiac repolarization processes and of the recovery sequence.
A computer model simulating both excitation and recovery processes within a block of heart muscle tissue has been developed and implemented on different IBM PC AT compatible computers. The model incorporates blocks of tissue consisting of several thousand elements and introduces phenomena which are completely or partly omitted in other existing cardiac electrophysiology models. These phenomena include the electric anisotropy of the tissue, different durations of repolarization in different layers of tissue, and the different shapes of action potential which correspond to cells excited when not fully recovered. Implementation of the model on small personal computers requires the use of a special data structure management and an effective algorithmic background. The program of the model is written in PASCAL and uses dynamically allocated data structures and the asynchronous simulation technique of event planing. These techniques are described in detail. The model has been used in various experiments. Results of simulation studies are presented in the form of modeled three-lead electrocardiographic records. The experimental series which are described include basic patterns of regular activation sequences, modeling of premature beats, simulation of effects due to fast pacing, models of ischemia and infarction, simulation of reentry mechanisms with a special reference to the initiation of ventricular fibrillation, and models of late potentials. The future development of more realistic models of the cardiac recovery process is also discussed.


The Effects of Acute Intracranial Pressure Changes on the Episcleral Venous Pressure, Retinal Vein Diameter and Intraocular Pressure in a Pig Model.
Orbital veins such as the retinal veins and episcleral veins drain into the cavernous sinus, an intracranial venous structure. We studied the effects of acute intracranial pressure (ICP) elevation on episcleral venous pressure, intraocular pressure and retinal vein diameter in an established non-survival pig model. In six adult female domestic pigs, we increased ICP in 5 mm Hg increments using saline infusion through a lumbar drain. We measured ICP (using parenchymal pressure monitor), intraocular pressure (using pneumatonometer), episcleral venous pressure (using venomanometer), retinal vein diameter (using OCT images) and arterial blood pressure at each stable ICP increment. The average baseline ICP was 5.4 mm Hg (range 1.5-9 mm Hg) and the maximum stable ICP ranged from 18 to 40 mm Hg. Linear mixed models with random intercepts were used to evaluate the effect of acute ICP increase on outcome variables. With acute ICP elevation, we found loss of retinal venous pulsation and increased episcleral venous pressure, intraocular pressure and retinal vein pressure in all animals. Specifically, acute ICP increase was significantly associated with episcleral venous pressure (β = 0.31; 95% CI 0.14-0.48, p < .001), intraocular pressure (β = 0.37, 95%CI 0.24-0.50; p < .001) and retinal vein diameter (β = 11.29, 95%CI 1.57-21.00; p = .03) after controlling for the effects of arterial blood pressure. We believe that the ophthalmic effects of acute ICP elevation are mediated by increased intracranial venous pressure producing upstream pressure changes within the orbital and retinal veins. These results offer exciting possibilities for the development of non-invasive ophthalmic biomarkers to estimate acute ICP elevations following significant neuro-trauma.


Galphaq reduces cAMP production by decreasing Galphas protein abundance.
The heterotrimeric guanine nucleotide-binding protein Galphaq transduces signals from heptahelical transmembrane receptors (e.g., alpha(1)-adrenergic, endothelin 1A, and angiotensin II) to stimulate generation of inositol-1,4,5-trisphosphate and diacylglycerol. In addition, Galphaq decreases cAMP production, through unknown mechanisms, and thus affects physiological responsiveness of cardiac myocytes and other cells. Here, we provide evidence that Galphaq expression increases Galphas ubiquitination, decreases Galphas protein content, and impairs basal and beta(1)-adrenergic receptor-stimulated cAMP production. These biochemical and functional changes are associated with Akt activation. Expression of constitutively active Akt also decreases Galphas protein content and inhibits basal and beta(1)-adrenergic receptor-stimulated cAMP production. Akt knockdown inhibits Galphaq-induced reduction of Galphas protein. In addition, MDM2, an E3 ubiquitin ligase, binds Galphas and promotes its degradation. Therefore, increased expression of Galphaq decreases cAMP production through Akt-mediated Galphas protein ubiquitination and proteasomal degradation.


Gastric cancer in a coal mining region.
A significant excess incidence of gastric cancer was previously reported in the coal mining counties of Utah for 1965-1969. A repeat study for the period 1970-1975 showed the rates to be close to expectation and are in line with the slight excess mortality reported by Creagan et al. from United States coal mining counties. A cluster of 12 cases out of 43 reported for the 11-year period occurred in 1965. Cases during 1966-1975 appear to have occurred at random by year. The previous suggestion that the high incidence of gastric cancer in Carbon and Emery Counties could be related to frequent exposure to coal-carrying hydrocarbons appears to be unwarranted.


Antidiarrhoeal activity of ethanol extract of the bark of Dalbergia lanceolaria.
The bark of Dalbergia lanceolaria was undertaken for evaluation of antidiarrhoeal activity in albino mice based on ethnobotanical lead. This bark was collected from Khanapur area of Western Ghats near Pune, Maharashtra, India. The successive solvent extraction of bark was carried out after drying, using petroleum ether (60-80 degrees C) and ethanol in soxhlet apparatus. The ethanol extract showed activity against castor oil, magnesium sulphate induced diarrhoea in albino mice. The extract was also studied for castor oil induced intraluminal fluid accumulation as well as charcoal transit in normal and barium chloride treated animals. The extract reduced significantly intraluminal fluid accumulation and intestinal motility.


[Germany-wide, Web-based ParaReg Registry for Lifelong Monitoring of People with Spinal Cord Injury: Data Model, Ethico-legal Prerequisites and Technical Implementation].
In Germany, treatment paths for patients with acute spinal cord injury (SCI) differ considerably depending on intrinsic, disease-specific and extrinsic factors. Which of these factors are associated with improved outcome with fewer subsequent complications and inpatient re-admissions is not clear. The German-wide, patient-centered, web-based ParaReg registry will be implemented to improve the long-term quality of patient care and the planning of treatment paths with increased cost-effectiveness. In the 2017-18 conceptualization phase, the data model of the registry was developed in an iterative process of the ParaReg steering committee together with the extended DMGP board and patient representatives. In ParaReg, routine social and medical data as well as internationally established neurological, functional and participation scores will be documented. The assignment of a unique patient ID allows a lifelong, cross-center documentation of inpatient stays in one of the 27 SCI centers organized in the German-speaking Medical Society for SCI (DMGP). The ParaReg data protection concept and patient information/consent are based on the Open Source Registry for Rare Diseases (OSSE) which were extended by GDPR-relevant aspects. In the realization phase, which started in 2019, the information technology infrastructure was implemented according to the clinical ID management module of the Technology and Methods Platform for Networked Medical Research (TMF). In parallel, the legal and ethical prerequisites for registry operation under the patronage of the DMGP were created. Recommendations of the working group data protection of the TMF were integrated into ParaReg's data protection concept. Based on the feedback from the alpha test phase with documentation of the hospitalization data of 40 patients, the ergonomics of the electronic case report forms were improved in particular for data entry on mobile devices. After completion of the monocentric alpha test phase, the multicenter data acquisition was started in 5 DMGP-SCI centers. The sustainability of ParaReg is ensured by the structural and financial support of the DMGP after expiry of the funding by the German Federal Ministry of Education and Research (BMBF).


Different implications of stigmata of recent hemorrhage in gastric and duodenal ulcers.
A prospective study was conducted to evaluate the prognostic value of stigmata of recent hemorrhage in patients with bleeding peptic ulcer. Of 193 patients suffering from peptic ulcer bleeding identified by emergency gastrointestinoscopy, 52 patients were found to have bleeding gastric ulcer (spurt 5, active oozing 9, fresh clot 11, black clot 17, protruding vessel 4, and clear base without stigmata 6); the other 141 had bleeding duodenal ulcer (spurt 5, active oozing 26, fresh clot 43, black clot 23, protruding vessel 15, and clear base without stigmata 31). Patient with continuous bleeding or rebleeding was grouped as unstable bleeders. The rate of unstable bleeders was 39.1% (continuous bleeding 23.9% and rebleeding 15.2%) in patients with gastric ulcer, compared to 9.0% (4.5% and 4.5%) in duodenal ulcer (P less than 0.001). The unstable bleeder rate of ulcers with spurt, active oozing, clot, and protruding vessel was 80%, 44%, 35.7%, and 0%, respectively, in patients with bleeding gastric ulcer; and 33.3%, 19.2%, 6%, and 0%, respectively, in patients with bleeding duodenal ulcer. The data suggest that the stigmata of recent hemorrhage, excluding protruding vessel, has prognostic significance in bleeding gastric ulcer but less in bleeding duodenal ulcer.


[Lioresal in the treatment of hemiplegia. Clinical and electromyographic evaluation. Preliminary report].
On the basis of an analysis of the clinical condition and electromyographic changes in 9 patients treated with Lioresal and 3 controls attention is called to the favourable effect of Lioresal in hemiparesis of cerebral origin. Lioresal was given in daily doses of 50 mg and no unfavourable side effects were observed. Reduction of muscular hypertonia and improvement of general motor activity was obtained.


Decomposition of alachlor by ozonation and its mechanism.
Decomposition and corresponding mechanism of alachlor, an endocrine disruptor in water by ozonation were investigated. Results showed that alachlor could not be completely mineralized by ozone alone. Many intermediates and final products were formed during the process, including aromatic compounds, aliphatic carboxylic acids, and inorganic ions. In evoluting these products, some of them with weak polarity were qualitatively identified by GC-MS. The information of inorganic ions suggested that the dechlorination was the first and the fastest step in the ozonation of alachlor.


Identification of patients in need of psychiatric intervention: visiting an emergency facility.
The utilization of the emergency room (E.R.) at a small community hospital located in a black inner-city area is investigated. Patients are classified according to a criterion for psychiatric intervention for the purpose of making staffing pattern recommendations. Psychiatric patients and non-psychiatric patients are classified by age, marital status, previous admissions to the E.R., time of arrival and time spent in the E.R., and circumstances of mode of arrival in the E.R. The criterion of psychiatric intervention is viewed as providing an additional dimension in the study of the emergency room, a hospital service which is providing increasing routine and non-routine medical care to the general population.


Longitudinal assessment of glomerular filtration rate by gamma camera and portable external detector.
Noninvasive isotope chelate methods to assess glomerular filtration rate (GFR) are less accurate than blood sampling. However, some measurement errors would be expected to be constant for an individual, and repeat estimations may be less variable. In 18 patients, estimates of GFR were obtained by 2 gamma camera techniques and a portable external detector at a mean interval of 1 year, to assess accuracy in predicting a change of GFR. Errors in these techniques were not significantly better than those predicted from two independent estimates. Most GFR measurement error for noninvasive methods appears to be random.


From Other Journals: A Review of Recent Articles by Our Editorial Team.
In this review, we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. This review includes (1) Fetal diagnosis, associated anomalies, and factors affecting outcomes in fetal congenitally corrected transposition of the great arteries (ccTGA), (2) The impact of Fontan-associated liver disease on heart and heart/liver transplant, (3) 1-year outcomes of the Harmony transcatheter pulmonary valve, (4) Risk factors associated with major adverse cardiac events in patients with pulmonary atresia and intact ventricular septum undergoing intervention, and (5) Benefits of pulmonary valve replacement in tetralogy of Fallot patients.


Anatomic ACL reconstruction: the normal central tibial footprint position and a standardised technique for measuring tibial tunnel location on 3D CT.
The aim of this study was to define the normal ACL central tibial footprint position and describe a standardised technique of measuring tibial tunnel location on 3D CT for anatomic single-bundle ACL reconstruction. The central position of the ACL tibial attachment site was determined on 76 MRI scans of young individuals. The central footprint position was referenced in the anterior-posterior (A-P) and medial-lateral (M-L) planes on a grid system over the widest portion of the proximal tibia. 3D CT images of 26 young individuals had a simulated tibial tunnel centred within the bony landmarks of the ACL footprint, and the same grid system was applied over the widest portion of the proximal tibia. The MRI central footprint position was compared to the 3D CT central footprint position to validate the technique and results. The median age of the 76 MRI subjects was 24 years, with 32 females and 44 males. The ACL central footprint position was at 39 (±3 %) and 48 (±2 %), in the A-P and M-L planes, respectively. There was no significant difference in this position between sexes. The median age of the 26 CT subjects was 25.5 years, with 10 females and 16 males. The central position of the bony ACL footprint was at 38 (±2 %) and 48 (±2 %), in the A-P and M-L planes, respectively. The MRI and CT central footprint positions were not significantly different in relation to the medial position, but were different in relation to the anterior position (A-P 39 % vs. 38 %, p = 0.01). The absolute difference between the central MRI and CT reference positions was 0.45 mm. The ACL's normal central tibial footprint reference position has been defined, and the technique of measuring tibial tunnel location with a standardised grid system is described. This study will assist surgeons in evaluating tibial tunnel position in anatomic single-bundle ACL reconstruction. III.


Renal artery thrombosis as a long-term complication of COVID-19.
Coronavirus disease 2019 (COVID-19) has been extensively associated with microvascular and macrovascular thrombosis. Several reports have demonstrated a link between COVID-19 and pulmonary embolism, deep vein thrombosis, myocardial infarction, stroke, and aortic thrombosis. Renal artery thrombosis is of special interest because of its life-threatening consequences, such as acute kidney injury and renal infarction. We present a case of left renal artery thrombosis as a long-term complication of COVID-19. Moreover, we demonstrate the effectiveness of interventional radiology to regain vascularization of the affected kidney.


The neurocognitive features in survival processing: An ERP study.
Recent behavioral studies used a survival processing task to investigate our memory systems from an evolutionary perspective. These results showed a memory advantage for the words rated for their relevance to a survival scenario compared with the words processed under numerous other tasks. However, the proximate explanations for the survival processing effect were mainly investigated through the subsequent retention data. By using event-related potentials, the present study was aimed to explore the neurocognitive features when we perform the survival-relevance-rating task. We used a pleasantness rating task and a moving processing task as control conditions in Experiments 1 and 2, respectively. Our results showed a larger parietal P600 for the words processed in the survival task compared with those processed in the pleasantness task and the moving task, indicating more elaborative encoding were obtained for the words processed in the survival task. Furthermore, an attenuated N400 was observed for the survival-relevant words in the survival task, indicating the survival scenario could facilitate the retrieval of these survival-relevant words. More importantly, a larger right frontal P600 was also observed for these survival-relevant words. This component might reflect the cognitive processes when we attempt to use the objects at hand to solve the fitness-relevant problems which we are facing. The present study supports the elaborative encoding hypothesis, and found the right frontal cortex plays an important role when we perform the survival task.


Identification of the receptor of oncolytic virus M1 as a therapeutic predictor for multiple solid tumors.
Over the last decade, oncolytic virus (OV) therapy has shown its promising potential in tumor treatment. The fact that not every patient can benefit from it highlights the importance for defining biomarkers that help predict patients' responses. As particular self-amplifying biotherapeutics, the anti-tumor effects of OVs are highly dependent on the host factors for viral infection and replication. By using weighted gene co-expression network analysis (WGCNA), we found matrix remodeling associated 8 (MXRA8) is positively correlated with the oncolysis induced by oncolytic virus M1 (OVM). Consistently, MXRA8 promotes the oncolytic efficacy of OVM in vitro and in vivo. Moreover, the interaction of MXRA8 and OVM studied by single-particle cryo-electron microscopy (cryo-EM) showed that MXRA8 directly binds to this virus. Therefore, MXRA8 acts as the entry receptor of OVM. Pan-cancer analysis showed that MXRA8 is abundant in most solid tumors and is highly expressed in tumor tissues compared with adjacent normal ones. Further study in cancer cell lines and patient-derived tumor tissues revealed that the tumor selectivity of OVM is predominantly determined by a combinational effect of the cell membrane receptor MXRA8 and the intracellular factor, zinc-finger antiviral protein (ZAP). Taken together, our study may provide a novel dual-biomarker for precision medicine in OVM therapy.


Pesticides measured in air and precipitation in the Yamaska Basin (Québec): occurrence and concentrations in 2004.
Air and precipitation samples were collected and analyzed for 91 pesticides or metabolites from May to September 2004 at St. Damase, an agricultural site located in Yamaska basin in Québec, Canada. A broad range of pesticides was detected during this experiment where 40 different compounds were measured. Most of the samples showed more than 10 simultaneous pesticide detections and sometimes reaching 19 simultaneous detections. The most detected pesticides in air were trifluralin, metolachlor and captan, which were found in all the samples during the 5 months of measurements. For the detected compounds, the average concentrations ranged from 4 pg/m3 to 8 ng/m3. Some of the pesticides detected in air were found in precipitation samples as well showing that wet deposition can occur and have an impact on aquatic ecosystems. The most important pesticides detected were related to corn and soya cultivations, the two main cultures in this region highlighting that the major sources come from local applications. On the other hand, the detection of some pesticides in precipitation which were undetectable in air implies that some compounds may have a long range transport origin.


Cost Effectiveness of Early Endovenous Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis in the United Kingdom.
Early clot removal using endovascular intervention aims to reduce post-thrombotic syndrome (PTS) following iliofemoral deep venous thrombosis (DVT). This may reduce long term morbidity but incurs a higher initial cost. This study examined the cost effectiveness of catheter directed thrombolysis (CDT) and pharmacochemical thrombectomy (PMT) compared with oral anticoagulation (OAC) alone for treatment of acute iliofemoral DVT in the United Kingdom. A combined decision tree (acute DVT complications) and Markov model (long term complications [PTS]) was used for decision analytic modelling with five states: no PTS, mild PTS, moderate PTS, severe PTS, and dead. All patients started with acute DVT. Patients who survived acute complications transitioned into the Markov model. Cycle time was six months. A healthcare payer perspective and lifetime horizon was used, adjusting for excess mortality due to history of thrombosis. Data for probabilities, transition probabilities, mortality, and utilities were obtained from the published literature. Cost data were obtained from UK NHS tariffs and published literature. Outcomes were mean lifetime cost, quality adjusted life years (QALYs), and cost effectiveness. Over a patient's lifetime, OAC was more costly (£37 206) than CDT (£32 043) and PMT (£36 288). Mean lifetime QALYs for OAC (12.9) were lower than CDT (13.5) and PMT (13.3). Therefore, in the incremental cost effectiveness analysis, both CDT and PMT were dominant: CDT was less costly (-£5 163) and more effective (+0.6 QALYs) than OAC, and PMT was also less costly (-£917) and more effective (+0.3 QALYs) than OAC. Results were robust to univariable sensitivity analyses, but probabilistic sensitivity analyses suggested considerable parameter uncertainty. Early interventional treatment of iliofemoral DVT is cost effective in the UK. Future clinical and epidemiological studies are needed to characterise parameter uncertainty. Further analysis of modern practice, alternative treatments, and optimised care models is warranted.


A Randomized Controlled Trial Offering Higher- Compared with Lower-Dairy Second Meals Daily in Preschools in Guinea-Bissau Demonstrates an Attendance-Dependent Increase in Weight Gain for Both Meal Types and an Increase in Mid-Upper Arm Circumference for the Higher-Dairy Meal.
Controversy remains over the most effective approaches to prevent childhood malnutrition. We tested the feasibility and effectiveness of delivering ready-to-use supplementary foods (RUSFs) as a second daily meal in preschool children aged 3-5 y in Guinea-Bissau, and compared RUSFs with different levels of dairy protein. This study was a 3 mo cluster-randomized controlled pilot trial of 2 RUSFs differing in dairy protein in 533 boys and girls from 9 preschools. Children receiving RUSFs were compared with wait-listed controls, and all students received a daily school lunch. The RUSFs were delivered 5 d/wk for 3 mo and contained 478 kcal and 11.5 g protein per 92-g daily serving. Deliveries included a ready-to-use supplementary food with 15% of protein from dairy sources (RUSF-15%) or one with 33% of protein from dairy sources (RUSF-33%). Intention-to-treat (ITT) and per-protocol analyses (>50 d of RUSF consumption) were conducted. Changes in the weight-for-age z score (WAZ) and height-for-age z score were primary outcomes. Additional outcomes included changes in mid-upper arm circumference (MUAC), hemoglobin, and retinol binding protein. Baseline anthropometry was not different between groups (WAZ, -0.48 ± 1.04) and increased significantly over time (P < 0.01) with no effects of the RUSFs in ITT analyses. However, children consuming RUSFs for >50 d had a significantly greater increase in WAZ relative to the increase in controls (+0.40 and +0.32 for RUSF-15% and RUSF-33%, respectively, compared with +0.24 in controls, P < 0.01 and P < 0.05, respectively). RUSF-33%, but not RUSF-15%, also eliminated a decrease in MUAC observed in controls (-0.01 cm in RUSF-33% compared with -0.34 cm in controls, P < 0.05). The only difference between RUSF-15% and RUSF-33% was a mean decrease in hemoglobin in children receiving RUSF-15% (-0.5 compared with -0.002 g/dL, P = 0.05). Implementation of 2-meal preschool feeding programs is feasible in low-income countries, and there are measurable benefits relative to 1-meal programs in children attending preschool regularly. In addition, MUAC and hemoglobin measurements indicate that meals with 33% compared with 15% of protein from dairy may help prevent wasting and anemia.


Natural killer T cells in patients with prostatic carcinoma.
Recent interest has focused on natural killer T (NKT) cells as effector cells in a possible new form of immunotherapy. NKT cells express T cell and natural killer cell receptors. They are CD1d-dependent and can be stimulated by alpha-galactosylceramide. We have studied peripheral blood levels of NKT cells simultaneously with CD8+ cells and natural killer cells in 54 patients with prostatic carcinoma. Levels of NKT cells in patients with androgen withdrawal and stable PSA levels were 211.8 +/- 138.4 cells/microl and in patients with rising PSA levels were 27.0 +/- 22.1 cells/microl. A similar but less pronounced difference in CD8+ cells between these groups was found (656.4 vs. 212.0 cells/microl). Comparing all 54 patients studied, a positive correlation was found between the levels of NKT cells and CD8+ cells (r = 0.83). Our results suggest an important and regulatory role of NKT cells in patients with prostatic carcinoma.


Effects of glyburide on in vivo insulin-mediated glucose disposal.
The purpose of this study was to examine the effects of glyburide on peripheral (muscle) and hepatic insulin sensitivity in patients with non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) as well as in healthy control subjects. In protocol 1, 10 patients with NIDDM and seven young healthy control subjects were studied. Changes in insulin sensitivity (40 mU/m2.min euglycemic insulin clamp), hepatic glucose production (3-[3H]glucose turnover), and insulin secretion (+125 mg/dL hyperglycemic clamp) were measured before and after 3 months (in patients with NIDDM) and 6 weeks (in young control subjects) of glyburide therapy. In protocol 2, five patients with IDDM and eight patients with insulin-treated NIDDM were evaluated before and after two months of glyburide therapy (20 mg per day). Changes in daily insulin requirements, 24-hour plasma glucose profiles, glycohemoglobin, glucagon-stimulated C-peptide secretion, insulin sensitivity, and hepatic glucose production were measured. In protocol 1, glyburide significantly improved insulin sensitivity (p less than 0.01) and insulin secretion (p less than 0.01) in the NIDDM patients. The elevated rates of hepatic glucose production (2.4 +/- 0.3 mg/kg.min) were reduced after glyburide therapy (1.7 +/- 0.2 mg/kg.min; p less than 0.01) and were highly correlated with an improvement in fasted plasma glucose levels (r = 0.92; p less than 0.001). Insulin sensitivity also improved in the young healthy control subjects after glyburide therapy (6.5 +/- 0.5 to 7.6 +/- 0.7 mg/kg.min; p less than 0.05). In protocol 2, glyburide treatment produced no change in daily insulin requirement (54 +/- 8 versus 53 +/- 7 units per day), mean 24-hour glucose levels (177 +/- 20 versus 174 +/- 29 mg/dL), glycohemoglobin (10.1 +/- 1.0 percent versus 9.5 +/- 7 percent), C-peptide secretion, insulin sensitivity, or basal hepatic glucose production (p values not significant) in the IDDM patients. In contrast, the insulin-treated NIDDM patients had significant reductions in mean daily insulin requirement (72 +/- 6 versus 58 +/- 9 units per day; p = 0.05), mean 24-hour plasma glucose levels (153 +/- 10 to 131 +/- 5 mg/dL; p less than 0.05), and glycohemoglobin levels (10.3 +/- 0.7 percent to 8.0 +/- 0.4 percent; p less than 0.05) and an improvement in C-peptide secretion (0.24 +/- 0.07 to 0.44 +/- 0.09 pmol/mL; p = 0.08). Stimulated C-peptide levels were highly correlated with a reduction in insulin dose observed during the 2-month treatment period (r = 0.93; p less than 0.001). Insulin sensitivity improved slightly but not significantly after glyburide treatment.(ABSTRACT TRUNCATED AT 400 WORDS)


Evaluation of the Vitek 2 system with a variety of Staphylococcus species.
The Vitek 2 gram-positive (GP) card was compared with an oligonucleotide array approach for the identification of 190 Staphylococcus strains, including 35 species, isolated from clinical and environmental specimens. The GP card provided a rapid and reliable identification of most species, whatever their origin.


Optic nerve involvement in dysthyroidism.
Although its prevalence in dysthyroidism is estimated at less than 5%, optic neuropathy should be recognized as a preventable cause of disabling visual loss. Obscured by more obvious external congestive signs, it is usually insidiously progressive and bilateral, but may be acute and unilateral. Neuro-ophthalmic findings are nonspecific (prechiasmal field defects, normal or swollen nerveheads), and the diagnosis should be suspected in the context of typical adnexal changes of dysthyroidism. Optic nerve involvement is probably secondary to apical orbital compression by congested muscles. Treatment with oral corticosteroids, irradiation, or orbital decompression has been beneficial, especially in the early phases.


miR-6769b-5p targets CCND-1 to regulate proliferation in cadmium-treated placental trophoblasts: Association with the impairment of fetal growth.
Environmental cadmium (Cd) is positively associated with placental impairment and fetal growth retardation. Nevertheless, its potential mechanisms remain unclear. microRNAs (miRNAs) are known to influence placental development and fetal growth. This work was aimed to determine which miRNAs are involved in Cd-impaired placental and fetal development based on the mRNA and miRNA expression profiles analysis. As a result, gestational Cd exposure deceased fetal and placental weight, and reduced the protein level of PCNA in human and mouse placentae. Furthermore, the results of mRNA microarray showed that Cd-downregulated mRNAs were predictively correlated with several biological processes, including cell proliferation, differentiation and motility. In addition, the results of miRNA microarray and qPCR assay demonstrated that Cd significantly increased the level of miR-6769b-5p, miR-146b-5p and miR-452-5p. Integrated analysis of Cd-upregulated miRNAs predicted target genes and Cd-downregulated mRNAs found that overlapping mRNAs, such as CCND1, CDK13, RINT1 and CDC26 were also significantly associated with cell proliferation. Further experiments showed that miR-6769b-5p inhibitor, but not miR-146b-5p and miR-452-5p, markedly reversed Cd-downregulated the expression of proliferation-related mRNAs, and thereby restored Cd-decreased the proteins level of CCND1 and PCNA in human placental trophoblasts. Dual luciferase reporter assay further revealed that miR-6769b-5p directly targets CCND1. Finally, the case-control study demonstrated that increased miR-6769b-5p level and impaired cell proliferation were observed in small-for-gestational-age human placentae. In conclusion, miR-6769b-5p targets CCND-1 to regulate proliferation in Cd-treated placental trophoblasts, which is associated with the impairment of fetal growth. Our findings imply that placental miR-6769b-5p may be used as an epigenetic marker for environmental pollutants-caused fetal growth restriction and its late-onset chronic diseases.