An Ultrasound Tomography Method for Monitoring CO2 Capture Process Involving Stirring and CaCO3 Precipitation.
In this work, an ultrasound computed tomography (USCT) system was employed to investigate the fast-kinetic reactive crystallization process of calcium carbonate. USCT measurements and reconstruction provided key insights into the bulk particle distribution inside the stirred tank reactor and could be used to estimate the settling rate and settling time of the particles. To establish the utility of the USCT system for dynamical crystallization processes, first, the experimental imaging tasks were carried out with the stirred solid beads, as well as the feeding and stirring of the CaCO3 crystals. The feeding region, the mixing process, and the particles settling time could be detected from USCT data. Reactive crystallization experiments for CO2 capture were then conducted. Moreover, there was further potential for quantitative characterization of the suspension density in this process. USCT-based reconstructions were investigated for several experimental scenarios and operating conditions. This study demonstrates a real-time monitoring and fault detection application of USCT for reactive crystallization processes. As a robust noninvasive and nonintrusive tool, real-time signal analysis and reconstruction can be beneficial in the development of monitoring and control systems with real-world applications for crystallization processes. A diverse range of experimental studies shown here demonstrate the versatility of the USCT system in process application, hoping to unlock the commercial and industrial utility of the USCT devices.


[Constancy of color perception in the gray toad (Bufo bufo L.): role of the surrounding background in recognition of stimulus color].
The paper continues the previous study (1) on some aspects of toad colour vision. It deals with signs which allow the visual system of toad to recognize blue stimuli. The behavioural experiments were performed during the breeding season when males exhibited the clasping of stationary blue stimuli. It is shown that in spite of some variety of spectral compositions of light sources males clasp only blue stimuli on white surrounding background. Under fixed illumination on white background males clasp blue stimuli, while on red and/or yellow background they clasp grey stimuli as well. These responses appear explicable if it is assumed that the surrounding background is the main sign of a spectral composition of illumination with "the simultaneous colour contrast" being a part of the constant colour perception mechanism (2).


The alcohol-tobacco relationship: a prospective study among adolescents in six European countries.
This study examined the earliest stages in drug involvement, in terms of the relationship between alcohol and tobacco use, among adolescents from six European countries (Denmark, Finland, the Netherlands, Portugal, Spain and the United Kingdom). International, gender and age differences were studied. A large international sample of European adolescents (n = 10170, mean age = 13.3 years) was followed longitudinally. Data were gathered in the autumn terms of 1998 and 1999 by means of self-administered questionnaires. Adolescents' self-reports on smoking and alcohol behaviour were used. Both behaviours were classified into two categories, that of adolescents who had never used the substance and that of those who had used the substance at least once in their lives. Logistic regression was used to determine which substance was the best predictor of the subsequent use of the other substance. Alcohol use and tobacco use were found to be associated with each other reciprocally. Results revealed that in Europe as a whole, tobacco use predicted subsequent alcohol use better than the converse. However, for Dutch girls, alcohol use predicted subsequent smoking behaviour better than the converse. The findings suggest that the development of alcohol and tobacco use patterns are closely related, but the order of progression is not universal and may reflect cultural factors.


Tropical myeloneuropathies revisited.
An interesting neurological syndrome, characterized by recurrent optic neuritis, cervical myelopathy from syringomyelia, paraparesis, amenorrhea-galactorrhea, and other endocrine problems, has been described among young black women in the French West Indies. The etiology remains unknown, but possible links with Devic's disease, acute disseminated encephalomyelitis, and neurotoxicity from quinolines in Annona muricata teas have been postulated. The largest epidemic of neuropathy in this century occurred in Cuba in 1991-1994. Clinical features and etiologic studies are reviewed. Its primary cause was nutritional. A similar epidemic was recently described in Tanzania. A number of infectious neuropathies and myopathies are reviewed, including leprosy, tuberculosis, hemorrhagic fevers (Ebola and Marburg filoviruses, Lassa, Argentinean and Bolivian arenaviruses), the human retrovirus human T-cell lymphotropic virus type I, Lyme disease and postimmunization neuropathies. The tropics continue to contribute interesting and important clinical conditions that may illuminate the etiopathiogenesis of other common disorders.


Recombination nodules and the mechanism of crossing-over in Drosophila.
Meiotic recombination involves a complex sequence of regulated enzymatic and structural functions. These functions and their possible interrelations are discussed using evidence mainly from studies on Drosophila.


Cost-Effectiveness of Long-Term Every Three-Year Versus Annual Postoperative Surveillance for Low-Risk Papillary Thyroid Cancer.
Patients with low-risk papillary thyroid cancer (PTC) who demonstrate an excellent response to initial therapy have a 2% recurrence rate and 100% disease-specific survival within 10 years. Thus, annual surveillance may be excessive. We hypothesized that less frequent postoperative surveillance in these patients is cost effective. A Markov discrete time state transition model was created to compare postoperative surveillance tapered to 3-year intervals after 5 years of annual surveillance versus conventional annual surveillance in low-risk PTC patients with negative neck ultrasound and stimulated thyroglobulin less than 2 ng/mL 1 year postoperatively. Outcome probabilities, utilities, and costs were determined via literature review, the Medicare Physician Fee Schedule, and Healthcare Cost and Utilization Project data. Sensitivity analyses were performed to assess areas of uncertainty. The cost of annual surveillance was $5,239 per patient and yielded 22.49 quality-adjusted life-years (QALYs). The 3-year strategy cost $2,601 less, but also yielded 0.01 less QALYs. Thus, the incremental cost per QALY of annual surveillance was $260,100. Probabilistic sensitivity analysis demonstrated that less frequent surveillance was more cost effective in 99.98% of 10,000 simulated patients. One-way sensitivity analysis revealed that annual surveillance would be cost effective if the total cost of neck ultrasound could be reduced to $23 or less. Extending postoperative surveillance to 3-year intervals after 5 years of annual surveillance in patients with low-risk PTC with excellent response to therapy is more cost effective than annual surveillance.


Effects of iodine on inducible nitric oxide synthase and cyclooxygenase-2 expression in sulfur mustard-induced skin.
In a previous study we demonstrated the protective effect of topical iodine as postexposure treatment for sulfur mustard (SM) application. The iodine treatment results in significantly reduced inflammation and necrosis and increased epidermal hyperplasia. The expression and localization of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in paraffin-embedded skin samples from that study were evaluated in the present investigation. We compared the immunoreactivity of iNOS and COX-2 using five samples from each of the following four test sites: untreated control sites, SM-exposed sites, sites treated with iodine mixture 15 min after SM exposure, and sites treated with iodine 30 min after SM exposure. All animals were killed 2 days after irritant exposure. iNOS immunoreactivity was present only in skin sites exposed to SM without iodine treatment. The ulcerated skin was covered with a relatively thick band of exudate composed of iNOS-immunostained polymorphonuclear cells and macrophages. In untreated skin, COX-2 immunostaining was limited to the thin suprabasal epidermal layer. In SM-exposed skin, induction of COX-2 was noted in inflammatory cells located close to the site of epidermal injury. In skin sites treated with iodine 15 or 30 min after SM exposure, the regenerating hyperplastic epithelium showed moderate cytoplasmic staining localized to the epithelium overlying the basal layer. This pattern of staining was also present in the nearby dermal fibroblasts. Thus, in contrast to the skin samples exposed to SM without iodine treatment, the epidermal layer expressing immunohistochemical positivity for COX-2 was thicker and corresponded to the epidermal hyperplasia noted in samples treated with iodine. It is well documented that prostaglandins (PGs) promote epidermal proliferation, thereby contributing to the repair of injured skin. That the induction of the COX-2 shown in our study may also play a role in the healing process is indicated by the present evidence. The results suggest that nitric oxide radicals (NO*) are involved in mediating the damage induced by the SM and that iodine-related reduction in acute epidermal inflammation is associated with reduced iNOS expression.


Recombinant polyclonal antibody libraries.
We describe a technology for generating recombinant polyclonal antibody libraries (PCALs) that enables the creation and perpetuation of standardized mixtures of polyclonal whole antibodies specific for a multiantigen (or polyantigen). Therefore, this technology combines the advantages of targeting multiple antigenic determinants -- high avidity, low likelihood of antigen 'escape variants', and efficient mediation of effector functions, with the advantages of using monoclonal antibodies -- unlimited supply of standardized reagents and the availability of the genetic material for desired manipulations. The technology for generating recombinant polyclonal antibody libraries begins with the creation of phage display Fab (antibody) libraries. This is followed by selection of sublibraries with desired antigen specificities, and mass transfer of the variable region gene pairs of the selected sublibraries to a mammalian expression vector for generation of libraries of polyclonal whole antibodies. We review here our experiments for selection of phage display antibody libraries against microbes and tumor cells, as well as the recent literature on the selection of phage display antibody libraries to multiantigen targets.


Activation by p-chloroamphetamine of the spinal ejaculatory pattern generator in anaesthetized male rats.
In urethane-anesthetized male rats, a branch of the hypogastric nerve was shown, anatomically and electrophysiologically, to supply the vas deferens. Recordings from this nerve revealed a low level of tonic activity, which was predominantly efferent motor activity. Administration of p-chloroamphetamine i.v., elicited a rhythmic burst of neuronal activity, coherent with rhythmic pressure increases in the vas deferens and contractions of the bulbospongiosus muscles, which together comprise ejaculation. This response to p-chloroamphetamine was still present after complete transection of the spinal cord at T8-T9. These data indicate that p-chloroamphetamine is capable of activating the spinal neuronal circuits that generate the pattern of autonomic and somatic responses similar to those of sexual climax. Furthermore based on the best documented action of p-chloroamphetamine, the results suggest that the excitability of the pattern generator is regulated by serotonergic, dopaminergic or noradrenergic receptors in the lumbosacral spinal cord. We conclude this animal model will enable robust studies of the pharmacology and physiology of central neural mechanisms involved in ejaculation and sexual climax.


Complex Aerosol Characterization by Scanning Electron Microscopy Coupled with Energy Dispersive X-ray Spectroscopy.
Particulate matter (PM) air pollution is a central concern for public health. Current legislation relies on a mass concentration basis, despite broad acceptance that mass alone is insufficient to capture the complexity and toxicity of airborne PM, calling for additional and more comprehensive measurement techniques. We study to what extent scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM/EDS) can be applied for physicochemical characterization of complex aerosols, and investigate its potential for separating particle properties on a single particle basis, even for nanosized particles. SEM/EDS analysis is performed on impactor samples of laboratory generated aerosols, consisting of either NaCl, Halloysite fibers, soot-like Printex90 agglomerates, or their combination. The analysis is automated and performed as EDS maps, covering a statistically relevant number of particles, with analysis times of approximately one hour/sample. Derived size distributions are compared to scanning mobility particle sizer (SMPS) and electric low-pressure impactor (ELPI) results. A method is presented to estimate airborne number concentrations and size distributions directly from SEM results, within a factor 10 of SMPS and ELPI outcomes. A classification scheme is developed based on elemental composition, providing class-specific information with individual particle statistics on shape, size, and mixing state. This can identify primary particles for source apportionment and enables easy distinction between fibrous and dense particle classes, e.g. for targeted risk assessments. Overall, the SEM/EDS analysis provides a more detailed physicochemical characterization of PM than online measurements, e.g. SMPS and ELPI. The method has the potential to improve assessments of PM exposure and risk, and facilitates source identification, even without prior knowledge at sampling.


Conformational Properties of Polymers at Droplet Interfaces as Model Systems for Disordered Proteins.
Polymer models serve as useful tools for studying the formation and physical properties of biomolecular condensates. In recent years, the interface dividing the dense and dilute phases of condensates has been discovered to be closely related to their functionality, but the conformational preferences of the constituent proteins remain unclear. To elucidate this, we perform molecular simulations of a droplet formed by phase separation of homopolymers as a surrogate model for the prion-like low-complexity domains. By systematically analyzing the polymer conformations at different locations in the droplet, we find that the chains become compact at the droplet interface compared with the droplet interior. Further, segmental analysis revealed that the end sections of the chains are enriched at the interface to maximize conformational entropy and are more expanded than the middle sections of the chains. We find that the majority of chain segments lie tangential to the droplet surface, and only the chain ends tend to align perpendicular to the interface. These trends also hold for the natural proteins FUS LC and LAF-1 RGG, which exhibit more compact chain conformations at the interface compared to the droplet interior. Our findings provide important insights into the interfacial properties of biomolecular condensates and highlight the value of using simple polymer physics models to understand the underlying mechanisms.


Antibiotic Resistance Genes in River Biofilms: A Metagenomic Approach toward the Identification of Sources and Candidate Hosts.
Treated wastewater is a major pathway by which antibiotic resistance genes (ARG) enter aquatic ecosystems. However, knowledge gaps remain concerning the dissemination of specific ARG and their association with bacterial hosts. Here, we employed shotgun metagenomics to track ARG and taxonomic markers in river biofilms along a gradient of fecal pollution depicted by crAssphage signatures. We found strong evidence for an impact of wastewater effluents on both community composition and resistomes. In the light of such simultaneity, we employed a model comparison technique to identify ARG-host relationships from nonassembled metagenomic DNA. Hereby, a major cause of spurious associations otherwise encountered in correlation-based ARG-host analyses was suppressed. For several families of ARG, namely those conferring resistance to beta-lactams, particular bacterial orders were identified as candidate hosts. The found associations of blaFOX and cphA with Aeromonadales or blaPER with Chromatiales support the outcome of independent evolutionary analyses and thus confirm the potential of the methodology. For other ARG families including blaIMP or tet, clusters of bacterial orders were identified which potentially harbor a major proportion of host species. For yet other ARG, like, for example, ant or erm, no particular host candidates were identifiable, indicating their spread across various taxonomic groups.


Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings.
Over half of adults in the United States report consuming dietary supplements. The US Food and Drug Administration (FDA) has warned of numerous dietary supplements containing undeclared, unapproved pharmaceutical ingredients. These FDA warnings have not been comprehensively analyzed for recent years. To summarize trends across adulterated (containing unapproved ingredients) dietary supplements associated with a warning released by the FDA from 2007 through 2016. In this quality improvement study, data were extracted from the FDA's Center for Drug Evaluation and Research, Tainted Products Marketed as Dietary Supplements_CDER database from 2007 through 2016. Data from each warning were recorded unless multiple warnings were issued for the same product within a 6-month period. Date, product name, company, hidden ingredient(s), product category, source of sample, and warning document type were recorded for each included warning. Data analysis was conducted from February 2017 to June 2017. From 2007 through 2016, 776 adulterated dietary supplements were identified by the FDA and 146 different dietary supplement companies were implicated. Most of these products were marketed for sexual enhancement (353 [45.5%]), weight loss (317 [40.9%]), or muscle building (92 [11.9%]), with 157 adulterated products (20.2%) containing more than 1 unapproved ingredient. The most common adulterants were sildenafil for sexual enhancement supplements (166 of 353 [47.0%]), sibutramine for weight loss supplements (269 of 317 [84.9%]), and synthetic steroids or steroid-like ingredients for muscle building supplements (82 of 92 [89.1%]). There were 28 products named in 2 or 3 warnings more than 6 months apart. Of these products, 19 (67.9%) were reported to contain new unapproved ingredients in the second or third warning, consistent with the assumption that the FDA found the product to be adulterated more than once. In recent years (2014-2016), 117 of 303 adulterated samples (38.6%) were identified through online sampling and 104 of 303 (34.3%) were identified through the examination of international mail shipments. Active pharmaceuticals continue to be identified in dietary supplements, especially those marketed for sexual enhancement or weight loss, even after FDA warnings. The drug ingredients in these dietary supplements have the potential to cause serious adverse health effects owing to accidental misuse, overuse, or interaction with other medications, underlying health conditions, or other pharmaceuticals within the supplement.


Virulence properties of extended spectrum β-lactamase-producing Klebsiella species in meat samples.
The present study was carried out to identify virulence properties (siderophores, serum resistance, and hemolysin) and antibiotic resistance in extended spectrum β-lactamase (ESBL)-producing Klebsiella isolates from 60 calf and chicken meat samples purchased from various supermarkets in Ankara, Turkey. Of the 45 Klebsiella isolates, 24 (53%) were identified as K. oxytoca and 21 (47%) were identified as K. pneumoniae. A high proportion of Klebsiella isolates had virulence factors such as hemolytic activity (67%), siderophore production (44%), and serum resistance (38%). The double-disk synergy test was used to determine ESBL production. ESBL production was detected in 13 (29%) of the 45 Klebsiella isolates. Resistance to 14 antimicrobials was tested in all Klebsiella isolates by the disk diffusion method. All isolates were resistant to two or more antimicrobial agents. All ESBL-producing Klebsiella isolates were highly resistant to cephalosporins and monobactams. Our findings indicate that meat and its products represent potential hazardous sources of multidrug-resistant and virulent Klebsiella species.


Sequence analysis of Leuconostoc mesenteroides bacteriophage Phi1-A4 isolated from an industrial vegetable fermentation.
Vegetable fermentations rely on the proper succession of a variety of lactic acid bacteria (LAB). Leuconostoc mesenteroides initiates fermentation. As fermentation proceeds, L. mesenteroides dies off and other LAB complete the fermentation. Phages infecting L. mesenteroides may significantly influence the die-off of L. mesenteroides. However, no L. mesenteroides phages have been previously genetically characterized. Knowledge of more phage genome sequences may provide new insights into phage genomics, phage evolution, and phage-host interactions. We have determined the complete genome sequence of L. mesenteroides phage Phi1-A4, isolated from an industrial sauerkraut fermentation. The phage possesses a linear, double-stranded DNA genome consisting of 29,508 bp with a G+C content of 36%. Fifty open reading frames (ORFs) were predicted. Putative functions were assigned to 26 ORFs (52%), including 5 ORFs of structural proteins. The phage genome was modularly organized, containing DNA replication, DNA-packaging, head and tail morphogenesis, cell lysis, and DNA regulation/modification modules. In silico analyses showed that Phi1-A4 is a unique lytic phage with a large-scale genome inversion ( approximately 30% of the genome). The genome inversion encompassed the lysis module, part of the structural protein module, and a cos site. The endolysin gene was flanked by two holin genes. The tail morphogenesis module was interspersed with cell lysis genes and other genes with unknown functions. The predicted amino acid sequences of the phage proteins showed little similarity to other phages, but functional analyses showed that Phi1-A4 clusters with several Lactococcus phages. To our knowledge, Phi1-A4 is the first genetically characterized L. mesenteroides phage.


[Method of analysing ethical conflicts in care practice].
In every clinical relationship decisions must be taken in conditions of uncertainty, which requires reasonableness and prudence. How is this to be done in the best way possible? By deliberating. The two most successful methodological proposals in the application of bioethics have been casuist and principalist, which have similar contents but different bases. In this article these proposals are applied to a practical case in which the withdrawal of life supporting treatment was posed. The analysis is carried out in four steps: the first is to realise, in the absence of malice, a clinical evaluation of the indication or indications for intervening medically. The second step takes us to the principle of justice or the contextual features, procuring an equitable share out of health resources. The third step refers to the principle of autonomy, that of the patients' preferences. This principle is the latest to emerge in health relationships and is probably the one that poses the most problems. Respect for the autonomy of the person affected implies considering three aspects: capacity, information and voluntariness. The fourth and final step deals with the principle of benefit or quality of life. This criterion is necessarily linked to the preferences of the patient himself and, besides, its general content includes attempt by the health practice to promote well-being, to assist and cure diseases, to promote and maintain health, to alleviate pain and suffering, to avoid premature death and to ensure a peaceful death. Deliberation and weighing up each of the contents of the above steps is the methodological proposal that is set forth, with the argument favouring the pre-eminence of one or another of the aspects depending on the data presented by each case.


[Fetopathy associated with exposure to angiotensin converting enzyme inhibitors].
Angiotensin Converting Enzyme Inhibitors (ACEI) are commonly used antihypertensive drugs, although contraindicated during pregnancy by fetopathy association such as renal dysgenesis, oligohydramnios, hipocalvaria, pulmonary hypoplasia, intrauterine growth restriction, and neonatal anuric renal failure. The authors present a clinical report of a child that developed neonatal anuric renal failure with peritoneal dialysis support by an in uterus exposure to ACEI with very good recovery. This case and literature review states the need to avoid ACEI prescription to Young women and it's suspension as soon as possible during pregnancy.


Persistent spin dynamics intrinsic to amplitude-modulated long-range magnetic order.
An incommensurate elliptical helical magnetic structure in the frustrated coupled-spin-chain system FeTe(2)O(5)Br is surprisingly found to persist down to 53(3) mK (T/T(N)~1/200), according to neutron scattering and muon spin relaxation. In this state, finite spin fluctuations at T→0 are evidenced by muon depolarization, which is in agreement with specific-heat data indicating the presence of both gapless and gapped excitations. We thus show that the amplitude-modulated magnetic order intrinsically accommodates contradictory persistent spin dynamics and long-range order and can serve as a model structure to investigate their coexistence.


Transforming family practice in British Columbia: the General Practice Services Committee.
To describe a new approach to primary care reform developed in British Columbia (BC) under the leadership of the General Practice Services Committee (GPSC). COMPOSITION OF THE COMMITTEE: The GPSC is a joint committee of the BC Ministry of Health Services, the BC Medical Association, and the Society of General Practitioners of BC. Representatives of BC's health authorities also attend as guests. This paper is based on the 2008-2009 annual report of the GPSC. It summarizes the history and main activities of the GPSC. The GPSC is currently supporting a number of key activities to transform primary care in BC. These activities include the Full Service Family Practice Incentive Program, which provides incentive payments to promote enhanced primary care; the Practice Support Program, which provides family physicians and their medical office assistants with various practical evidence-based strategies and tools for managing practice enhancement; the Family Physicians for BC Program to develop family practices in areas of identified need; the Shared Care Committee, which supports and enables the determination of appropriate scopes of practice among GPs, specialists, and other health care professionals; the Divisions of Family Practice, which are designed to facilitate interactions among family doctors and between doctors and their respective health authorities; and the Community Healthcare and Resource Directory, a Web-based resource to help health care providers find appropriate mental health resources. Early results indicate that the GPSC's initiatives are enhancing the delivery of primary care services in BC.


Acute liver failure in Cuban children.
Acute liver failure is rare in pediatric patients and is one of the most challenging medical emergencies due to its prognostic and therapeutic implications. The best scientific evidence worldwide comes from multicenter studies in developed countries. In Cuba, there are no prior studies of this disorder in children. Describe the main clinical features of Cuban children treated at a national referral center for acute liver failure, as defined by recognized diagnostic criteria for pediatric patients. A case series study was conducted comprising patients diagnosed with acute liver failure treated from 2005 to 2011 in the hepatology and liver transplant service at Havana's William Soler University Children's Hospital. Variables were age group, etiology of acute liver failure, grade of hepatic encephalopathy, blood chemistry variables, and clinical outcome (whether or not spontaneous recovery of liver function occurred). Associations between variables were assessed using contingency tables, and case fatality was calculated, as well as relative risk with its 95% confidence interval. The Mann-Whitney U test was used to compare means of laboratory test results. Median age of the 31 patients studied (14 boys and 17 girls) was 24 months (range 1-180). Time between symptom onset and diagnosis of acute liver failure was 25.1 days (SD 16.8). Infection was the most common etiology, present in 61.3% of cases (19/31); nonhepatotropic viruses, especially cytomegalovirus, predominated in infants. Spontaneous recovery occurred in 15 patients (48.4%), 3 (9.7%) received transplants, and 13 died, for a case fatality of 41.9%. Outcome was not associated with etiology (p = 0.106), but was statistically associated with degree of hepatic encephalopathy (p <0.01): 77.8% of patients (7/9) with grades III-IV encephalopathy died, for a relative risk of 4.0 (95% CI 1.15-13.8), versus 11.1% (1/9) with grade II or less encephalopathy. Cholesterol levels were significantly lower in patients who failed to recover spontaneously (p <0.01). Patients' clinical characteristics in this case series were similar to those described in developed countries.The fact that nonhepatotropic viruses (basically, cytomegalovirus in infants) are the main cause of acute liver failure in Cuban children calls for further epidemiologic study and identification of local underlying determinants of this phenomenon.


Pregnancies after Childhood Craniopharyngioma: Results of KRANIOPHARYNGEOM 2000/2007 and Review of the Literature.
Data on female fertility, pregnancy, and outcome of offspring after childhood-onset craniopharyngioma (CP) are rare. Observational study on pregnancy rate and offspring outcome in female CP patients recruited in KRANIOPHARYNGEOM 2000/2007 since 2000. A total of 451 CP patients (223 female) have been recruited, and 269 (133 female) were postpubertal at study. Six of 133 female CP patients (4.5%) with a median age of 14.9 years at CP diagnosis had 9 pregnancies, giving birth to 10 newborns. Three patients achieved complete surgical resections. No patient underwent postoperative irradiation. Five natural pregnancies occurred in 3 CP patients without pituitary deficiencies. Four pregnancies in 3 CP patients with hypopituitarism were achieved under assisted reproductive techniques (ART) (median 4.5 cycles, range: 3-6 cycles). Median maternal age at pregnancy was 30 years (range: 22-41 years). Six babies (60%) were delivered by caesarean section. Median gestational age at delivery was 38 weeks (range: 34-43 weeks); median birth weight was 2,920 g (range: 2,270-3,520 g), the rate of preterm delivery was 33%. Enlargements of CP cysts occurred in 2 women during pregnancy. Other complications during pregnancy, delivery, and postnatal period were not observed. Pregnancies after CP are rare and were only achieved after ART in patients with hypopituitarism. Close monitoring by an experienced reproductive physician is necessary. Due to a potentially increased risk for cystic enlargement, clinical, ophthalmological, and MRI monitoring are recommended in patients at risk. Severe perinatal complications, birth defects, and postnatal morbidity of mothers and offspring were not observed.


Structures of a deAMPylation complex rationalise the switch between antagonistic catalytic activities of FICD.
The endoplasmic reticulum (ER) Hsp70 chaperone BiP is regulated by AMPylation, a reversible inactivating post-translational modification. Both BiP AMPylation and deAMPylation are catalysed by a single ER-localised enzyme, FICD. Here we present crystallographic and solution structures of a deAMPylation Michaelis complex formed between mammalian AMPylated BiP and FICD. The latter, via its tetratricopeptide repeat domain, binds a surface that is specific to ATP-state Hsp70 chaperones, explaining the exquisite selectivity of FICD for BiP's ATP-bound conformation both when AMPylating and deAMPylating Thr518. The eukaryotic deAMPylation mechanism thus revealed, rationalises the role of the conserved Fic domain Glu234 as a gatekeeper residue that both inhibits AMPylation and facilitates hydrolytic deAMPylation catalysed by dimeric FICD. These findings point to a monomerisation-induced increase in Glu234 flexibility as the basis of an oligomeric state-dependent switch between FICD's antagonistic activities, despite a similar mode of engagement of its two substrates - unmodified and AMPylated BiP.


The impact of obesity, sex, and diet on hepatic glucose production in cats.
Obesity is a risk factor for type 2 diabetes in cats. The risk of developing diabetes is severalfold greater for male cats than for females, even after having been neutered early in life. The purpose of this study was to investigate the role of different metabolic pathways in the regulation of endogenous glucose production (EGP) during the fasted state considering these risk factors. A triple tracer protocol using (2)H(2)O, [U-(13)C(3)]propionate, and [3,4-(13)C(2)]glucose was applied in overnight-fasted cats (12 lean and 12 obese; equal sex distribution) fed three different diets. Compared with lean cats, obese cats had higher insulin (P < 0.001) but similar blood glucose concentrations. EGP was lower in obese cats (P < 0.001) due to lower glycogenolysis and gluconeogenesis (GNG; P < 0.03). Insulin, body mass index, and girth correlated negatively with EGP (P < 0.003). Female obese cats had approximately 1.5 times higher fluxes through phosphoenolpyruvate carboxykinase (P < 0.02) and citrate synthase (P < 0.05) than male obese cats. However, GNG was not higher because pyruvate cycling was increased 1.5-fold (P < 0.03). These results support the notion that fasted obese cats have lower hepatic EGP compared with lean cats and are still capable of maintaining fasting euglycemia, despite the well-documented existence of peripheral insulin resistance in obese cats. Our data further suggest that sex-related differences exist in the regulation of hepatic glucose metabolism in obese cats, suggesting that pyruvate cycling acts as a controlling mechanism to modulate EGP. Increased pyruvate cycling could therefore be an important factor in modulating the diabetes risk in female cats.


Analysis of transient receptor potential ankyrin 1 (TRPA1) in frogs and lizards illuminates both nociceptive heat and chemical sensitivities and coexpression with TRP vanilloid 1 (TRPV1) in ancestral vertebrates.
Transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1 (V1) perceive noxious temperatures and chemical stimuli and are involved in pain sensation in mammals. Thus, these two channels provide a model for understanding how different genes with similar biological roles may influence the function of one another during the course of evolution. However, the temperature sensitivity of TRPA1 in ancestral vertebrates and its evolutionary path are unknown as its temperature sensitivities vary among different vertebrate species. To elucidate the functional evolution of TRPA1, TRPA1s of the western clawed (WC) frogs and green anole lizards were characterized. WC frog TRPA1 was activated by heat and noxious chemicals that activate mammalian TRPA1. These stimuli also activated native sensory neurons and elicited nocifensive behaviors in WC frogs. Similar to mammals, TRPA1 was functionally co-expressed with TRPV1, another heat- and chemical-sensitive nociceptive receptor, in native sensory neurons of the WC frog. Green anole TRPA1 was also activated by heat and noxious chemical stimulation. These results suggest that TRPA1 was likely a noxious heat and chemical receptor and co-expressed with TRPV1 in the nociceptive sensory neurons of ancestral vertebrates. Conservation of TRPV1 heat sensitivity throughout vertebrate evolution could have changed functional constraints on TRPA1 and influenced the functional evolution of TRPA1 regarding temperature sensitivity, whereas conserving its noxious chemical sensitivity. In addition, our results also demonstrated that two mammalian TRPA1 inhibitors elicited different effect on the TRPA1s of WC frogs and green anoles, which can be utilized to clarify the structural bases for inhibition of TRPA1.


The effect of passive listening versus active observation of music and dance performances on memory recognition and mild to moderate depression in cognitively impaired older adults.
The study examined the effects of music therapy and dance/movement therapy on cognitively impaired and mild to moderately depressed older adults. Passive listening to music and active observation of dance accompanied by music were studied in relation to memory enhancement and relief of depressive symptoms in 100 elderly board and care residents. The Beck Depression Inventory and the Recognition Memory Test-Faces Inventory were administered to two groups (one group exposed to a live 30-min. session of musical dance observation, the other to 30 min. of pre-recorded music alone) before the intervention and measured again 3 and 10 days after the intervention. Scores improved for both groups on both measures following the interventions, but the group exposed to dance therapy had significantly lower Beck Depression scores that lasted longer. These findings suggest that active observation of Dance Movement Therapy could play a role in temporarily alleviating moderate depressive symptoms and some cognitive deficits in older adults.


Production of 15O for Medical Applications via the 16O(γ,n)15O Reaction.
15O (half-life, 122 s) is a useful radionuclide for PET applications. Current production of 15O typically makes use of the 14N(d,n)15O, 15N(p,n)15O, or 16O(p,pn)15O reactions using an accelerator. A novel approach for the production of 15O is via the 16O(γ,n)15O reaction using an electron linear accelerator. Photonuclear reactions using an electron linear accelerator may allow for feasible and economical production of 15O compared with the current methods. Methods: In this work, experiments using a repurposed Clinac were conducted using oxygen-containing alumina as a target material to study the production rate of 15O. Additional studies were conducted using a water target cell. Simulations using Geant4 were conducted to predict the activity and power dissipation in the target. Results: Bremsstrahlung radiation from the electron beam, and consequently 15O production via photonuclear reactions, is enhanced when a high-Z material, tungsten, is placed in front of the target. The alumina irradiations provided preliminary data to optimize the beam parameters and target configuration. The optimal thickness of tungsten was 1.4 mm for both the simulated and the measured studies of alumina. Simulations of irradiated water targets showed that tungsten thicker than 1.4 mm resulted in fewer photons available to activate the water; thus, a higher current was required to achieve a fixed dose. Alternatively, for a constant tungsten thickness, more power was deposited in the target with increasing beam energy, requiring a lower current to achieve a fixed dose. Actual irradiations of a water target yielded a quantity of 15O in the water that was consistent with expectations based on irradiations of alumina. Conclusion: Several parameters should be considered regarding the photonuclear production of 15O for an average patient dose of 1,850 MBq (50 mCi) in 10 mL. This work illustrates a variety of machine parameters capable of achieving a reasonable patient dose. Our simulations show that the power deposited in the target for these parameters is less than that in commercially operated cyclotron targets for the production of 18F. Thus, this work demonstrates that the photonuclear production of 15O may be a new production path for this useful radionuclide.


Zellweger syndrome: biochemical and morphological studies on two patients treated with clofibrate.
Two infants with Zellweger syndrome (cerebro-hepato-renal syndrome) have been studied biochemically and morphologically. Peroxisomal enzymes involved in respiration, fatty acid beta-oxidation, and plasmalogen biosynthesis were assessed. In liver, catalase was present in normal amounts but was located in the cell cytosol. Dihydroxyacetone phosphate acyltransferase activity was less than one-tenth of normal. The amount of the bifunctional protein catalyzing two beta-oxidation reactions was found by immunoblotting to be greatly reduced. Catalase activity was normal in intestine. D-Amino acid oxidase was subnormal in kidney. The observed enzyme deficiencies may plausibly explain many of the metabolite imbalances observed clinically. Morphologically, peroxisomes were absent from liver. In intestine, normal peroxisomes were also missing, but some rare, smaller (0.04-0.13 micrometer) bodies were seen with a slight positive cytochemical reaction for catalase. These results, together with current concepts of peroxisome biogenesis, suggest but do not prove, that the primary defect in Zellweger syndrome may be in peroxisome assembly. The infants were treated with clofibrate, but it was ineffectual as assessed biochemically, morphologically, and clinically.


Caveolin-1 deficiency protects against mesangial matrix expansion in a mouse model of type 1 diabetic nephropathy.
Glomerular matrix protein accumulation, mediated largely by resident mesangial cells (MCs), is central to the pathogenesis of diabetic nephropathy. We previously showed that caveolin (CAV)-1/caveolae mediate matrix upregulation by MCs in response to high glucose and TGFβ, two important pathogenic mediators of diabetic glomerular sclerosis. Here, we evaluated the in vivo role of CAV-1/caveolae in the development of diabetic nephropathy. Diabetes was induced in Cav1-knockout (KO) mice and their wild-type (WT) counterparts by streptozotocin injection. After 10 months, kidneys were evaluated for the development of nephropathy, including glomerular sclerosis and upregulation of matrix proteins. Parallel experiments assessing glucose-induced matrix upregulation were carried out in MCs isolated from KO mice. KO diabetic mice developed hyperglycaemia and renal hypertrophy, but were protected from developing albuminuria and glomerular sclerosis compared with WT mice. KO mice were significantly protected from the upregulation of glomerular collagen I, fibronectin, connective tissue growth factor (CTGF) and TGFβ. In vitro, glucose induced collagen I A1 promoter activation and collagen I, fibronectin and CTGF protein upregulation in WT but not KO MCs. Re-expression of Cav1 in KO cells restored this response. Cav1 deletion rendered significant protection from glomerular matrix accumulation and albuminuria in a mouse model of type 1 diabetes. These studies provide a foundation for the development of renal-targeted interference with CAV-1/caveolae as a novel approach to the treatment of diabetic nephropathy.


Smartphones and tooth brushing: content analysis of the current available mobile health apps for motivation and training.
Smartphone mobile app is an innovative concept for health behaviour-based interventions. The present study aimed to analyse apps developed for smartphones that promote tooth brushing amongst children using the Coventry, Aberdeen, and London-Refined (CALO-RE) taxonomy for behaviour change. Tooth brushing apps available in English and free to download that purported to assist with brushing were searched on the Apple app store using search terms based on Boolean logic and included AND combinations for keywords tooth brushing, children, toothbrush and motivation in the health and fitness category; six apps met the inclusion criteria and were downloaded. The behaviour change taxonomies were assessed individually for each app and scored as per coding and analysed for presence or absence. Only three of the behaviour change taxonomies were present in all apps, i.e. information provision (general), goal setting (behaviour) and prompt practice. Setting graded tasks, self-monitoring of behavioural outcome, demonstration of behaviour, prompt use of imagery and time management were included in four out of six apps. The present study explores a new arena for oral healthcare motivation and prevention in children through the use of mobile phone apps.


Systemic effects of wood smoke in a short-term experimental exposure study of atopic volunteers.
To investigate whether short-term systemic effects of wood smoke occurred in atopic subjects after experimental wood smoke exposures. A double-blind climate chamber study was conducted on 20 healthy atopic subjects with exposures to filtered air and wood smoke. Pneumoproteins, coagulation and adhesion factors, and cytokines were measured. Heart rate was monitored with pulse monitors. Data were analyzed with mixed models. Few differences in the outcomes were observed. Plasma tissue factor remained elevated during filtered air exposure (P = 0.002). P-selectin declined independent of exposure (P = 0.0006). Interleukin-6 increased after filtered air (P = 0.03). The study confirmed previous observations among nonatopics of limited changes after a 3-hour wood smoke exposure.


Prevalence and Pattern of Alcohol Consumption using Alcohol Use Disorders Identification Test (AUDIT) in Rural Tamil Nadu, India.
There is a paucity of information on prevalence and pattern of alcohol consumption in India. To assess the prevalence and pattern of alcohol consumption in a rural area of Tamil Nadu, India. A community based, cross sectional study was conducted among 946 subjects who were aged 10 years and above, in rural Tamil Nadu, India. Data on alcohol use was collected by using 'Alcohol Use Disorder Identification Test' (AUDIT) scale. Data on pattern and associated factors like socio-demographic details, smoking, tobacco chewing and chronic diseases were collected by using a structured questionnaire. Data was analysed by univariate and multiple logistic regression analysis and information was depicted in percentages or proportions. A p value of less than 0.05 was considered as significant. Overall, the prevalence of alcohol use was found to be 9.4%. Prevalence was more among males (16.8%) as compared to that among females (1.3%). Mean age at initiation was 25.3 +9.0 years. Multiple logistic regression analysis revealed that middle age (15-44 years) (OR=3.56), male gender (OR=11.23), illiteracy (OR=6.16), lower education levels (OR=2.57) and smoking (OR=17.78) were independently associated with alcohol use. Among those who used alcohol, 29.2% (26) were possible hazardous drinkers, 33.7%(30) had a probable alcohol dependence and 56.2% (50) had experienced harmful effects, based on AUDIT item analysis. Prevalence of alcohol use is high, especially among males. Health educational interventions among those who are at a higher risk and management of alcohol dependent subjects, may help in reducing the burden of alcohol use in this area.


King Chulalongkorn: biography and his activities in medicine and public health.
King Rama V, or Chulalongkorn, was the fifth monarch of the Chakri Dynasty. He was one of the most beloved of the Thai kings due to his many activities including abolishing slavery without bloodshed and especially his skillful diplomacy which succeeded in steering Siam out of the grips of the colonial powers. His activities also included reform of the administration of the kingdom according to the European model and in bringing Siam into the modern era with such exquisite skills that he is still vividly remembered today. His reign also saw many developments in medicine and public health. The King's role in these areas, however, were clouded by his more visible activities in politics and diplomacy. The result is that the Thai public learned rather little about his role in these areas. This article aims at collecting this and to show the King's very important role in modernizing medicine and public health in Siam.


Modes of tracheal gas insufflation. Comparison of continuous and phase-specific gas injection in normal dogs.
Tracheal gas insufflation (TGI) improves the efficiency of CO2 elimination accomplished by conventional mechanical ventilation, primarily by reducing the anatomic (series) dead space volume. Dead space proximal to the catheter tip can be reduced by two methods. Fresh gas introduced at the carinal level during inspiration may effectively "bypass" the upper airway. Alternatively, proximal dead space can be "washed out" with fresh gas during expiration to reduce CO2 rebreathing. We examined these two modes of TGI-aided dead space reduction in nine paralyzed normal dogs receiving conventional mechanical ventilation and compared these results to those obtained with a catheter that delivered fresh gas continuously at the same flow rate, thereby accomplishing both bypass and washout. Total inspired tidal volume and cycling frequency were held constant. Differences in CO2 elimination efficiency among the TGI modes were flow dependent. Continuous catheter flow at 5 or 10 L/min reduced PaCO2 and physiologic dead space fraction (VD/VT) more than either proximal bypass or end-expiratory washout (p < 0.001). At the same catheter flow settings expiratory washout tended to improve VD/VT more than did inspiratory bypass. Under the conditions tested, constant tracheal insufflation of fresh gas improves alveolar ventilation by mechanisms that include, but are not limited to, a functional reduction in the dead space proximal to the catheter tip.


Vaccine-Hesitant and Vaccine-Refusing Parents' Reflections on the Way Parenthood Changed Their Attitudes to Vaccination.
Having children compels parents to examine their vaccine beliefs, particularly if they are vaccine-hesitant or refuse all vaccines. Presently, little is known about the specific ways in which having children influences the vaccine beliefs of parents. This research examined how having children changed the attitudes of Australian vaccine-hesitant and vaccine-refusing parents towards childhood vaccination. We asked 904 Australian parents who believed that having children changed their attitudes to vaccination to describe these changes. Parents' responses were inductively, iteratively coded and thematically analysed. Themes were compared between parents who believed all vaccines should be refused, parents with varying degrees of vaccine hesitancy, and parents who were fully vaccine-accepting. Low numbers of responses from fully vaccine-accepting parents meant that this paper focused on mostly vaccine-hesitant and vaccine-refusing vaccine parents. Five themes were identified. Having children prompted all parents to learn about vaccine choices. Hesitant and refusing parents' interpreted vaccine choices through a lens of distrust of pharmaceutical companies and regulatory bodies overseeing vaccine safety. The distrust fuelled parents' fears about vaccination risks, such as side effects. Parents became concerned about the scheduled timing of vaccinations, particularly of the Hepatitis B vaccine. Parents among the three groups that believed some or all vaccines should be refused reported that a vaccine permanently injured their child. This research contributes to understanding how having children affects the vaccine attitudes among vaccine-hesitant and vaccine-refusing parents. Greater support for parents with negative vaccination experiences may prevent hesitant attitudes. The vaccination schedule needs to be communicated to parents better.


Appraisal of the effect of brain impregnation duration on neuronal staining and morphology in a modified Golgi-Cox method.
Golgi-Cox staining method is considered as one of the best neurohistological and fascinating staining techniques to reveal the cytoarchitecture of the brain. Requirement of longer time (more than a month), laborious section processing steps, requirement of sophisticated equipment's and costly ready to use kits limits extensive use of this technique. The need for a modified staining technique is to overcome some of these hurdles. Here we describe a modification of Golgi-Cox staining involving reduced impregnation time (7 days), omitting tissue dehydration steps, and alterations in section processing steps. Different impregnation duration (7 days, 14 days, 1 month, 6 months and 10 months) effects on optimized staining of dorsal hippocampus and basolateral amygdala were investigated. Modified Golgi-Cox staining method was found to be effective in staining rat hippocampus and amygdala. Impregnation for 7 days, 14 days and 1 month resulted in giving good results and they were comparable. However, artifacts were slightly elevated with 6 months group but not extensively. Impregnation for 10 months negatively affected the staining process. Compared to existing methods the current method was found to be cost effective, fast, reliable and can be executed in labs where infrastructure is limited. Current modification considerably benefitted in obtaining better results (good clarity and lesser artifact) in a short time. Longer impregnated brain sections were found to be unsuitable for morphometric evaluation due to more stain precipitation and artifact. The modified technique can be used to study cellular architecture in other brain regions.


[Diagnosis of Erdheim-Chester disease following a traumatic fracture].
We describe the case of a woman with the diagnosis of Erdheim-Chester disease following an upper limb traumatic fracture. A 65-year-old woman presents to the emergency department for left shoulder and right ankle pain, she admits recent multiple falls. Imaging shows a left trochiter fracture and osteosclerotic lesions in the upper and lower limbs. Bone biopsy confirms the suspicion of Erdheim-Chester disease. Erdheim-Chester disease is a rare systemic non- Langerhans cell histiocytosis of the middle-aged adult. The most common characteristic is bilateral and symmetric osteosclerotic lesions in long bones. Pathological examination provides the definitive diagnosis. Imaging and clinical biology assess the extent of the disease. Treatment must be decided on a case-to-case basis taking into account patient's symptoms.


A computational model for designing energy behaviour change interventions.
The conflicting evidence in the literature on energy feedback as a driver for energy behaviour change has lead to the realization that it is a complex problem and that interventions must be proposed and evaluated in the context of a tangled web of individual and societal factors. We put forward an integrated agent-based computational model of energy consumption behaviour change interventions based on personal values and energy literacy, informed by research in persuasive technologies, environmental, educational and cognitive psychology, sociology, and energy education. Our objectives are: (i) to build a framework to accommodate a rich variety of models that might impact consumption decisions, (ii) to use the simulation as a means to evaluate persuasive technologies in-silico prior to deployment. The model novelty lies in its capacity to connect the determinants of energy related behaviour (values, energy literacy and social practices) and several generic design strategies proposed in the area of persuasive technologies within one framework. We validate the framework using survey data and personal value and energy consumption data extracted from a 2-year field study in Exeter, UK. The preliminary evaluation results demonstrate that the model can predict energy saving behaviour much better than a random model and can correctly estimate the effect of persuasive technologies. The model can be embedded into an adaptive decision-making system for energy behaviour change.


The microRNA bantam regulates a developmental transition in epithelial cells that restricts sensory dendrite growth.
As animals grow, many early born structures grow by cell expansion rather than cell addition; thus growth of distinct structures must be coordinated to maintain proportionality. This phenomenon is particularly widespread in the nervous system, with dendrite arbors of many neurons expanding in concert with their substrate to sustain connectivity and maintain receptive field coverage as animals grow. After rapidly growing to establish body wall coverage, dendrites of Drosophila class IV dendrite arborization (C4da) neurons grow synchronously with their substrate, the body wall epithelium, providing a system to study how proportionality is maintained during animal growth. Here, we show that the microRNA bantam (ban) ensures coordinated growth of C4da dendrites and the epithelium through regulation of epithelial endoreplication, a modified cell cycle that entails genome amplification without cell division. In Drosophila larvae, epithelial endoreplication leads to progressive changes in dendrite-extracellular matrix (ECM) and dendrite-epithelium contacts, coupling dendrite/substrate expansion and restricting dendrite growth beyond established boundaries. Moreover, changes in epithelial expression of cell adhesion molecules, including the beta-integrin myospheroid (mys), accompany this developmental transition. Finally, endoreplication and the accompanying changes in epithelial mys expression are required to constrain late-stage dendrite growth and structural plasticity. Hence, modulating epithelium-ECM attachment probably influences substrate permissivity for dendrite growth and contributes to the dendrite-substrate coupling that ensures proportional expansion of the two cell types.


Transglutaminase 1 stabilizes beta-actin in endothelial cells correlating with a stabilization of intercellular junctions.
Microvascular endothelial monolayers from mouse myocardium become resistant to various barrier-compromising stimuli correlating with the expression of transglutaminase 1 (TGase1) and its translocation towards cellular junctions. In contrast, endothelial monolayers from mouse lung microvessels do not express TGase1 and remain sensitive to barrier-compromising stimuli corresponding to the known in vivo sensitivity of the lung microvasculature. Using the TGase-substrate 5-(biotinamido)-pentylamine, specific TGase inhibitors and RNAi, one target protein of TGase1 in endothelial cells was found to be beta-actin, suggesting that tissue-specific stabilization of the cortical actin filament network by intracellular TGase1 activity may play a role in controlling barrier properties of endothelial monolayers.


Purine receptor P2Y6 mediates cellular response to γ-ray-induced DNA damage.
We previously showed that nucleotide P2 receptor agonists such as ATP and UTP amplify γ-ray-induced focus formation of phosphorylated histone H2A variant H2AX (γH2AX), which is considered to be an indicator of DNA damage so far, by activating purine P2Y6 and P2Y12 receptors. Therefore, we hypothesized that these P2 receptors play a role in inducing the repair response to γ-ray-induced DNA damage. In the present study, we tested this idea by using human lung cancer A549 cells. First, reverse-transcription polymerase chain reaction (RT-PCR) showed that P2Y6 receptor is highly expressed in A549 cells, but P2Y12 receptor is only weakly expressed. Next, colony formation assay revealed that P2Y6 receptor antagonist MRS2578 markedly reduced the survival rate of γ-ray-exposed A549 cells. The survival rate was also significantly reduced in P2Y6-knock-down cells, compared with scramble siRNA-transfected cells. Since it has reported that phosphorylation of ERK1/2 after activation of EGFR via P2Y6 and P2Y12 receptors is involved in the repair response to γ-ray-induced DNA damage, we next examined whether γ-ray-induced phosphorylation of ERK1/2 was also inhibited by MRS2578 in A549 cells. We found that it was. Taken together, these findings indicate that purinergic signaling through P2Y6 receptor, followed by ERK1/2 activation, promotes the cellular repair response to γ-ray-induced DNA damage.


Sleep deprivation increases A1 adenosine receptor binding in the human brain: a positron emission tomography study.
It is currently hypothesized that adenosine is involved in the induction of sleep after prolonged wakefulness. This effect is partially reversed by the application of caffeine, which is a nonselective blocker of adenosine receptors. Here, we report that the most abundant and highly concentrated A1 subtype of cerebral adenosine receptors is upregulated after 24 h of sleep deprivation. We used the highly selective A1 adenosine receptor (A1AR) radioligand [18F]CPFPX ([18F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine) and quantitative positron emission tomography to assess cerebral A1ARs before and after sleep deprivation in 12 healthy volunteers and a control group (n = 10) with regular sleep. In sleep deprived subjects, we found an increase of the apparent equilibrium total distribution volume in a region-specific pattern in all examined brain regions with a maximum increase in the orbitofrontal cortex (15.3%; p = 0.014). There were no changes in the control group with regular sleep. This is the first molecular imaging study that provides in vivo evidence for an A1AR upregulation in cortical and subcortical brain regions after prolonged wakefulness, indicating that A1AR expression is contributing to the homeostatic sleep regulation.


Recent Advances in the Detection of Food Toxins Using Mass Spectrometry.
Edibles are the only source of nutrients and energy for humans. However, ingredients of edibles have undergone many physicochemical changes during preparation and storage. Aging, hydrolysis, oxidation, and rancidity are some of the major changes that not only change the native flavor, texture, and taste of food but also destroy the nutritive value and jeopardize public health. The major reasons for the production of harmful metabolites, chemicals, and toxins are poor processing, inappropriate storage, and microbial spoilage, which are lethal to consumers. In addition, the emergence of new pollutants has intensified the need for advanced and rapid food analysis techniques to detect such toxins. The issue with the detection of toxins in food samples is the nonvolatile nature and absence of detectable chromophores; hence, normal conventional techniques need additional derivatization. Mass spectrometry (MS) offers high sensitivity, selectivity, and capability to handle complex mixtures, making it an ideal analytical technique for the identification and quantification of food toxins. Recent technological advancements, such as high-resolution MS and tandem mass spectrometry (MS/MS), have significantly improved sensitivity, enabling the detection of food toxins at ultralow levels. Moreover, the emergence of ambient ionization techniques has facilitated rapid in situ analysis of samples with lower time and resources. Despite numerous advantages, the widespread adoption of MS in routine food safety monitoring faces certain challenges such as instrument cost, complexity, data analysis, and standardization of methods. Nevertheless, the continuous advancements in MS-technology and its integration with complementary techniques hold promising prospects for revolutionizing food safety monitoring. This review discusses the application of MS in detecting various food toxins including mycotoxins, marine biotoxins, and plant-derived toxins. It also explores the implementation of untargeted approaches, such as metabolomics and proteomics, for the discovery of novel and emerging food toxins, enhancing our understanding of potential hazards in the food supply chain.


Self-assembly of molecular ions via like-charge ion interactions and through-space defined organic domains.
Reaction stoichiometry, dynamic light scattering, and DFT are used to explore tertiary ammonium bicarbonates that exist as ideal solutes and those that self-assemble. Self-assembling tertiary amines featured organic surfaces beyond a through-space defined sphere around the charge center. Like-charge hydrogen-bonded ion pairs (or anti-electrostatic hydrogen bonding (AEHB)) also play a role in the self-assembly and provide the first evidence of this bonding motif by bicarbonate in aqueous solution. A single crystal neutron structure of a tertiary ammonium bicarbonate featuring a bicarbonate dimer is presented.


Oral replacement of water and electrolyte losses due to travellers' diarrhoea.
An oral rehydration solution (ORS) containing glucose, sodium and potassium chloride, and sodium bicarbonate, forms the basis of an oral rehydration therapy (ORT) regime which is detailed. The regime can be modified for adults, older children, younger children and neonates, and may be used in combination with other methods of augmented fluid intake such as juices and plain water supplements. Milk and soft foods should be added to the regimen. Guidelines for patients include methods of assessing rehydration. The harmful effects of 'therapeutic' starvation are stressed.


Developing a molecular roadmap of drug-food interactions.
Recent research has demonstrated that consumption of food -especially fruits and vegetables- can alter the effects of drugs by interfering either with their pharmacokinetic or pharmacodynamic processes. Despite the recognition of such drug-food associations as an important element for successful therapeutic interventions, a systematic approach for identifying, predicting and preventing potential interactions between food and marketed or novel drugs is not yet available. The overall objective of this work was to sketch a comprehensive picture of the interference of ∼ 4,000 dietary components present in ∼1800 plant-based foods with the pharmacokinetics and pharmacodynamics processes of medicine, with the purpose of elucidating the molecular mechanisms involved. By employing a systems chemical biology approach that integrates data from the scientific literature and online databases, we gained a global view of the associations between diet and dietary molecules with drug targets, metabolic enzymes, drug transporters and carriers currently deposited in DrugBank. Moreover, we identified disease areas and drug targets that are most prone to the negative effects of drug-food interactions, showcasing a platform for making recommendations in relation to foods that should be avoided under certain medications. Lastly, by investigating the correlation of gene expression signatures of foods and drugs we were able to generate a completely novel drug-diet interactome map.


Age-Related Pathology Associated with H1N1 A/California/07/2009 Influenza Virus Infection.
Influenza virus infection causes a spectrum of diseases, ranging from mild upper respiratory tract infection to severe lower respiratory tract infection, that can lead to diffuse alveolar damage, interstitial and airspace inflammation, or acute respiratory failure. Mechanisms instructing disease severity are not completely understood, but host, viral, and bacterial factors influence disease outcome. With age being one host factor associated with a higher risk of severe influenza, we investigated regional pulmonary distribution and severity of pneumonia after 2009 H1N1 influenza virus infection in newly weaned, adult, and aged ferrets to better understand age-dependent susceptibility and pathology. Aged ferrets exhibited greater weight loss and higher rates of mortality than adult ferrets, whereas most newly weaned ferrets did not lose weight but had a lack of weight gain. Newly weaned ferrets exhibited minimal pneumonia, whereas adult and aged ferrets had a spectrum of pneumonia severity. Influenza virus-induced pneumonia peaked earliest in adult ferrets, whereas aged ferrets had delayed presentation. Bronchial severity differed among groups, but bronchial pathology was comparable among all cohorts. Alveolar infection was strikingly different among groups. Newly weaned ferrets had little alveolar cell infection. Adult and aged ferrets had alveolar infection, but aged ferrets were unable to clear infection. These different age-related pneumonia and infection patterns suggest therapeutic strategies to treat influenza should be tailored contingent on age.


Overexpression of the FAD-binding domain of the sulphite reductase flavoprotein component from Escherichia coli and its inhibition by iodonium diphenyl chloride.
SiR-FP43, the NADPH- and FAD-binding domain of the Escherichia coli sulphite reductase flavoprotein component (SiR-FP), has been overexpressed and characterized. It folds independently, retaining FAD as a cofactor and the catalytic properties associated with the presence of this cofactor. Iodonium diphenyl chloride (IDP) was shown to be a very efficient inhibitor of SiR-FP43 and SiR-FP60, the monomeric form of SiR-FP, containing both FMN and FAD as cofactors (K(i) = 18.5 +/- 5 microM, maximal inactivation rate = 0.053 +/- 0.005 s(-1)). In both cases, inactivation was shown to result from covalent binding of a phenyl group to FAD exclusively, in marked contrast with previous results obtained with cytochrome P450 reductase (CPR), where FMN and a tryptophan were phenylated, but not FAD. However, our kinetic analyses are in agreement with the inhibition mechanism demonstrated with CPR [Tew (1993) Biochemistry 32, 10209-10215]. Nine different FAD phenylated adducts were isolated and, for the first time, two FAD phenylated adducts were identified directly after extraction from a protein. Taken together, our results have shown that flavoprotein inactivation by IDP is not a reliable indicator for a flavin radical intermediate in catalysis.


Effects of surface curvature and surface chemistry on the structure and activity of proteins adsorbed in nanopores.
The interactions of proteins with the surface of cylindrical nanopores are systematically investigated to elucidate how surface curvature and surface chemistry affect the conformation and activity of confined proteins in an aqueous, buffered environment. Two globular proteins, lysozyme and myoglobin, with different catalytic functions, were used as model proteins to analyze structural changes in proteins after adsorption on ordered mesoporous silica SBA-15 and propyl-functionalized SBA-15 (C(3)SBA-15) with carefully controlled pore size. Liquid phase ATR-FTIR spectroscopy was used to study the amide I and II bands of the adsorbed proteins. The amide I bands showed that the secondary structures of free and adsorbed protein molecules differ, and that the secondary structure of the adsorbed protein is influenced by the local geometry as well as by the surface chemistry of the nanopores. The conformation of the adsorbed proteins inside the nanopores of SBA-15 and C(3)SBA-15 is strongly correlated with the local geometry and the surface properties of the nanoporous materials, which results in different catalytic activities. Adsorption by electrostatic interaction of proteins in nanopores of an optimal size provides a favorably confining and protecting environment, which may lead to considerably enhanced structural stability and catalytic activity.


[Perception of color and volumetric shape of objects].
The problem of recognition of coloration of volume objects, illuminated simultaneously with bright point ans weak diffuse sources (having arbirary and previously unknown spectra) is considered. A mathematical model, in which a process of recognition of coloration is accompanied by determining orientations of surface elements relatively the point source is described. The information on orientation allows in many cases to calculate the volume shape of objects of the external world form their monocular ""retinal"" image.


Planned Subtotal Resection of Vestibular Schwannoma Differs from the Ideal Radiosurgical Target Defined by Adaptive Hybrid Surgery.
To retrospectively compare ideal radiosurgical target volumes defined by a manual method (surgeon) to those determined by Adaptive Hybrid Surgery (AHS) operative planning software in 7 patients with vestibular schwannoma (VS). Four attending surgeons (3 neurosurgeons and 1 ear, nose, and throat surgeon) manually contoured planned residual tumors volumes for 7 consecutive patients with VS. Next, the AHS software determined the ideal radiosurgical target volumes based on a specified radiotherapy plan. Our primary measure was the difference between the average planned residual tumor volumes and the ideal radiosurgical target volumes defined by AHS (dRVAHS-planned). We included 7 consecutive patients with VS in this study. The planned residual tumor volumes were smaller than the ideal radiosurgical target volumes defined by AHS (1.6 vs. 4.5 cm3, P = 0.004). On average, the actual post-operative residual tumor volumes were smaller than the ideal radiosurgical target volumes defined by AHS (2.2 cm3 vs. 4.5 cm3; P = 0.02). The average difference between the ideal radiosurgical target volume defined by AHS and the planned residual tumor volume (dRVAHS-planned) was 2.9 ± 1.7 cm3, and we observed a trend toward larger dRVAHS-planned in patients who lost serviceable facial nerve function compared with patients who maintained serviceable facial nerve function (4.7 cm3 vs. 1.9 cm3; P = 0.06). Planned subtotal resection of VS diverges from the ideal radiosurgical target defined by AHS, but whether that influences clinical outcomes is unclear.


Psychological Adaptive Mechanism Maturity, Age, and Depression Symptoms in Advanced-Stage Cancer Patients.
Background: Previously, we reported that the maturity of Psychological Adaptive Mechanism (PAM; alternatively, ego defense mechanism) endorsement, but not depression symptom severity, predicted 5-year survival rates in adult cancer patients and that study controlled for age as a significant variable. In this investigation, we hypothesized that greater PAM maturity would correlate significantly with age and with fewer depression symptoms in a larger sample. Methods: In this cross-section study, adult cancer outpatients (N=293) completed the Defense Style Questionnaire (DSQ), the Beck Depression Inventory (BDI), and provided additional clinical data. Spearman's correlation and multiple regression modeling provided statistical tests of the study hypotheses. Results: Contrary to our hypothesis, DSQ PAM maturity endorsement did not correlate significantly with increasing age. Greater PAM maturity ratio on the DSQ (p<0.0001) and current antidepressant use (p<0.05), however, both provided inverse associations with total BDI symptom frequency (p<0.01). Age was inversely associated with BDI mood (p<0.0001) and somatic scores (p<0.04). Items that worsened BDI symptom frequency included self-reported mood-altering anti-cancer medications and any psychiatric history. Cancer stage, time since diagnosis, and chemotherapy treatment did not correlate with DSQ or BDI scores. Multiple regression analysis found that the correlated items accounted for 17.2% of the variance in mood symptoms and 4.9% in somatic symptoms. Specifically, adaptive maturity and age associated with fewer depression symptoms, while cancer medications affecting mood, and a previous psychiatric history each predicted higher frequency of depression scores. Conclusion: The results suggest that PAM maturity likely predicts fewer depression symptoms while younger age associates with more depression symptoms in this clinical sample. Centrally, acting cancer medications, such as glucocorticoids, and any history of psychiatric disorder correlated with increased depression symptom frequencies. In this cross-section study, antidepressant medications indicated higher frequencies of depressive symptoms, likely reflecting their use in persons previously diagnosed with depression. Further research should target factors that improve PAM maturity as a potential treatment target, especially in younger age groups.


A systematic review of work interventions to promote safe patient handling and movement in the healthcare sector.
Objectives. The aim of this systematic review was to describe interventions which promote safe patient handling and movement (PHM) among workers in healthcare by reviewing the literature on their effectiveness for work and health-related outcomes. Methods. Databases were searched for studies published during 1997-2018. Measures were operationalized broadly, capturing outcomes of work and health. Only randomized controlled trials (RCTs) and cohort studies with a control group were included. Quality was assessed using evidence-based checklists by the Swedish Agency for Health Technology Assessment and Assessment of Social Services. Results. The systematic review included 10 RCTs and 19 cohort studies. Providing work equipment and training workers is effective: it can increase usage. Training workers to be peer coaches is associated with fewer injuries. Other effective strategies are participatory ergonomics and management engagement in collaboration with workers, facilitating safe PHM. Conclusions. This systematic review suggests that interventions for safe PHM with an impact of health-related outcomes should include access to work equipment, training as well as employer and employee engagement. The additional impact of multifaceted interventions is inconclusive.


Optimizing antimicrobial therapy in urinary tract infections: A focus on urine culture and sensitivity testing.
Objectives: This cross-sectional study was conducted at Jordan university hospital to evaluate the impact of microbial culture data and sensitivity results on optimizing UTI treatment. Methods: All positive urine cultures requested for adult patients (≥18 years) admitted to Jordan University Hospital (JUH) within the period from January 2019-July 2021 were evaluated. The antibiotics prescribed before and after culture data and sensitivity results were compared to evaluate the impact of these diagnostic measures on optimizing UTI treatment. Results: During the study period, 2400 urine cultures revealed positive results. Among those patients, 1,600 (66.7%) were discharged before the availability of culture results and excluded. Of the remaining 800 patients, 701 patients (87.6%) received empiric treatment. After culture and sensitivity results were available, overall, 84 (10.5%) patients had optimization (improvement) in their UTI management after culture results were known, while 6 (0.8%) patients had a worsening in their treatments. Based on the culture results, we found that only 12.4% of patients were appropriately treated before and after the culture results. Moreover, our results revealed that 31.9% were inappropriately treated for their UTIs before and after culture results. Conclusion: This study revealed an alarmingly high rate of inappropriate treatment of UTIs despite the availability of urine culture and sensitivity data, and that culture results were not used to optimize treatment strategies for UTI. This practice can potentially result in poor health-related outcomes and adversely affects efforts to battle AMR. Multifaceted strategies must be implemented to help clinicians follow the best current evidence and current guidelines in their selection of antibiotics for the management of UTIs.


Disinfection behavior of a UV-treated wastewater system using constructed wetlands and the rate of reactivation of pathogenic microorganisms.
The use of constructed wetlands as a wastewater treatment system is a feasible solution for rural areas. However, these systems do not efficiently eliminate pathogenic microorganisms. Therefore, it is necessary to implement disinfection systems such as ultraviolet (UV) disinfection systems in constructed wetlands. To evaluate the behavior of a UV system, a pilot system of artificial wetlands connected to one such disinfection system was operated. The results show that when the total suspended solids (TSS) of the influent (already treated by the system of constructed wetlands) reached values of 26.7 mg/L, a reduction of 2.03 uLog in fecal coliforms was obtained. However, when the TSS increased to 34.7 mg/L, the reduction was only 0.33 uLog. In addition to the influence of the TSS on the fecal coliform reduction efficiency, there is a direct relationship between the transmittance and the sizes of the particles present in the influent. After UV treatment, the microorganisms showed a peak in photoreactivation of 27.8% at 4 h after irradiation with visible radiation, while under conditions of darkness, no reactivation was observed.


Chronic obstructive pulmonary disease: molecular and cellular mechanisms.
Chronic obstructive pulmonary disease is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective. There is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterised by increased numbers of alveolar macrophages, neutrophils and cytotoxic T-lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence for involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases. The inflammation and proteolysis in chronic obstructive pulmonary disease is an amplification of the normal inflammatory response to cigarette smoke. This inflammation, in marked contrast to asthma, appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.


We predict a riot: inequity, relative deprivation and collective destruction in the laboratory.
Riots are unpredictable and dangerous. Our understanding of the factors that cause riots is based on correlational observations of population data, or post hoc introspection of individuals. To complement these accounts, we developed innovative experimental techniques, investigated the psychological factors of rioting and explored their consequences with agent-based simulations. We created a game, 'Parklife', that physically co-present participants played using smartphones. In two teams, participants tapped on their screen to grow trees and flowerbeds on separate but adjacent virtual parks. Participants could also tap to vandalize the other team's park. In some conditions, we surreptitiously introduced inequity between the teams so that one (the disadvantaged team) had to tap more for each reward. The experience of inequity caused the disadvantaged team to engage in more destruction, and to report higher relative deprivation and frustration. Agent-based models suggested that acts of destruction were driven by the interaction between individual level of frustration and the team's behaviour. Our results provide insights into the psychological mechanisms underlying collective action.


Joint epigenome profiling reveals cell-type-specific gene regulatory programmes in human cortical organoids.
Gene expression is regulated by multiple epigenetic mechanisms, which are coordinated in development and disease. However, current multiomics methods are frequently limited to one or two modalities at a time, making it challenging to obtain a comprehensive gene regulatory signature. Here, we describe a method-3D genome, RNA, accessibility and methylation sequencing (3DRAM-seq)-that simultaneously interrogates spatial genome organization, chromatin accessibility and DNA methylation genome-wide and at high resolution. We combine 3DRAM-seq with immunoFACS and RNA sequencing in cortical organoids to map the cell-type-specific regulatory landscape of human neural development across multiple epigenetic layers. Finally, we apply a massively parallel reporter assay to profile cell-type-specific enhancer activity in organoids and to functionally assess the role of key transcription factors for human enhancer activation and function. More broadly, 3DRAM-seq can be used to profile the multimodal epigenetic landscape in rare cell types and different tissues.


The relationship between insight and the level of expressed emotion in patients with obsessive-compulsive disorder.
The aim of this study is firstly to compare the obsessive-compulsive disorder (OCD) patients with good insight and OCD patients with poor insight in terms of socio-demographic and clinical features; to investigate the relation between insight and the level of the expressed emotion (EE) in the patients; and lastly to specify the factors that predict level of insight. OCD patients with good insight and patients with poor insight were compared in terms of clinical features and the perceived EE level of the patients and the individuals that they live with in order to specify the factors that predict the insight level, and to investigate the relationship between insight level and EE. It was found that the total Expressed Emotion Scale, total Level of Expressed Emotion (LEE), LEE-Emotional Response and LEE-Tolerance/Expectation subscale scores of the group comprised of patients with poor insight are higher than the other group. The results also show that the duration of illness and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score predict insight level. This study shows that the level of EE perceived by the patients with poor insight and the person that he/she lives with, is higher than the group with good insight. The studies that investigate the relationship between the factors of insight level and EE level, which are indicated to determine the level of the illness severity and its chronicity, will enable the researchers to understand the importance of the role of the family on the treatment processes of OCD.


Intracellular tryptophan pool sizes may account for differences in gamma interferon-mediated inhibition and persistence of chlamydial growth in polarized and nonpolarized cells.
Gamma interferon (IFN-gamma) is an important factor in the modulating inhibition of intracellular chlamydial growth and persistence. In human epithelial cells and macrophages, this inhibition is the result of depletion of the essential amino acid tryptophan via the IFN-gamma-induced enzyme indoleamine 2, 3-dioxygenase. Under these conditions, chlamydiae must successfully compete with the host cell for limited resources in order to maintain viability. We provide evidence to support the hypothesis that the host cell polarization state influences the host-pathogen interplay and outcome of IFN-gamma-mediated inhibition. In polarized cells, intracellular soluble tryptophan pools were larger than those in nonpolarized cells despite only small differences in the initial uptake rate of this amino acid compared to that in nonpolarized cells. Furthermore, in Chlamydia trachomatis-infected cells, the amounts of tryptophan consumed by the organisms were similar for cells grown in either state. We propose that intracellular tryptophan pool sizes can account for differences in IFN-gamma-mediated chlamydial persistence and growth inhibition in polarized and nonpolarized cells. Collectively, these results argue that polarized cell models, which more accurately reflect the conditions in vivo, may be more relevant than conventionally cultured cells in the study of intimate intracellular host-parasite interactions.


Nutrient movement and removal in a switchgrass biomass-filter strip system treated with dairy manure.
Manure use on cropland has raised concern about nutrient contamination of surface and ground waters. Warm-season perennial grasses may be useful in filter strips to trap manure nutrients and as biomass feedstock for nutrient removal. We explored the use of 'Alamo' switchgrass (Panicum virgatum L.) in a biomass production-filter strip system treated with dairy manure. We measured changes in extractable P in the soil, NO3 -N in soil water, and changes in total reactive P and chemical oxygen demand (COD) of runoff water before and after a switchgrass filter strip. Five rates of dairy manure (target rates of 0, 50, 100, 150, and 200 kg N ha(-1) from solid manure in 1995; 0, 75, 150, 300, and 600 kg N ha(-1) from lagoon effluent in 1996 and 1997) were surface-applied to field plots of switchgrass (5.2 by 16.4 m) with a 5.2- by 16.4-m switchgrass filter strip below the manured area. Yield of switchgrass from the manured area increased linearly with increasing manure rate in each year. Soil water samples collected at 46 or 91 cm below the soil surface on 30 dates indicated < 3 mg L(-1) of NO3-N in all plots. Concentrations of total reactive P in surface runoff water were reduced an average of 47% for the 150 kg N rate and 76% for the 600 kg N rate in 1996 and 1997 after passing through the strip. Manure could effectively substitute for inorganic fertilizer in switchgrass biomass production with dual use of the switchgrass as a vegetative filter strip.


The DNA Damage Response in Neurons: Die by Apoptosis or Survive in a Senescence-Like State?
Neurons are exposed to high levels of DNA damage from both physiological and pathological sources. Neurons are post-mitotic and their loss cannot be easily recovered from; to cope with DNA damage a complex pathway called the DNA damage response (DDR) has evolved. This recognizes the damage, and through kinases such as ataxia-telangiectasia mutated (ATM) recruits and activates downstream factors that mediate either apoptosis or survival. This choice between these opposing outcomes integrates many inputs primarily through a number of key cross-road proteins, including ATM, p53, and p21. Evidence of re-entry into the cell-cycle by neurons can be seen in aging and diseases such as Alzheimer's disease. This aberrant cell-cycle re-entry is lethal and can lead to the apoptotic death of the neuron. Many downstream factors of the DDR promote cell-cycle arrest in response to damage and appear to protect neurons from apoptotic death. However, neurons surviving with a persistently activated DDR show all the features known from cell senescence; including metabolic dysregulation, mitochondrial dysfunction, and the hyper-production of pro-oxidant, pro-inflammatory and matrix-remodeling factors. These cells, termed senescence-like neurons, can negatively influence the extracellular environment and may promote induction of the same phenotype in surrounding cells, as well as driving aging and age-related diseases. Recently developed interventions targeting the DDR and/or the senescent phenotype in a range of non-neuronal tissues are being reviewed as they might become of therapeutic interest in neurodegenerative diseases.


Design and experiment of a shovel-tooth removal end-effector for abnormal plants in hybrid rape breeding based on MBD-DEM coupling.
In view of the problem that removing abnormal plants in breeding rape requires a large amount of labor and is inefficient, combined with the planting requirements of breeding rape, a shovel-tooth end-effector was designed, and a shovel-tooth removal test bench was built. A simulation model based on MBD (Multibody Dynamics)-DEM (Discrete Element Method) coupling was constructed. Then we conducted a Box-Behnken test with four factors and three levels. Taking the angle of soil penetration, speed of soil penetration, depth of soil penetration and speed of shovel-tooth gathering as the test factors, the soil penetration force and shovel-tooth gathering force as the test indicators. The mathematical regression model between test indicators and test factor was established. After optimizing the parameters of the model, the best combination of parameters with low soil penetration force and low shovel-tooth gathering force was obtained: angle of soil penetration of 84°, speed of soil penetration of 9 cm/s, depth of soil penetration of 8cm, and speed of shovel-tooth gathering of 6 cm/s. The simulation model was validated by field experiments. The average soil penetration force and average shovel-tooth gathering force of the three groups of pull-out tests were 34.8 N and 763.0 N, respectively. The removal rates were 96%, 92%, and 94%, all greater than 90%, indicating that the removal effect of the shovel-tooth end-effector was good, and the parameters were reasonably designed. The results can serve as reference for the design of rape abnormal plants removal device and the operation of MBD-DEM coupling simulation end-effector.


A practical method to determine the heating and cooling curves of x-ray tube assemblies.
A practical method to determine the heating and cooling curves of x-ray tube assemblies with rotating anode x-ray tube is proposed. Available procedures to obtain these curves as described in the literature are performed during operation of the equipment, and the precision of the method depends on the knowledge of the total energy applied in the system. In the present work we describe procedures which use a calorimetric system and do not require the operation of the x-ray equipment. The method was applied successfully to a x-ray tube assembly that was under test in our laboratory.


Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake.
A reduced risk for Parkinson's disease (PD) among cigarette smokers has been observed consistently during the past 30 years. Recent evidence suggests that caffeine may also be protective. Findings are presented regarding associations of PD with smoking, caffeine intake, and alcohol consumption from a case-control study conducted in western Washington State in 1992-2000. Incident PD cases (n = 210) and controls (n = 347), frequency matched on gender and age were identified from enrollees of the Group Health Cooperative health maintenance organization. Exposure data were obtained by in-person questionnaires. Ever having smoked cigarettes was associated with a reduced risk of PD (odds ratio (OR) = 0.5, 95% confidence interval (CI): 0.4, 0.8). A stronger relation was found among current smokers (OR = 0.3, 95% CI: 0.1, 0.7) than among ex-smokers (OR = 0.6, 95% CI: 0.4, 0.9), and there was an inverse gradient with pack-years smoked (trend p < 0.001). No associations were detected for coffee consumption or total caffeine intake or for alcohol consumption. However, reduced risks were observed for consumption of 2 cups/day or more of tea (OR = 0.4, 95% CI: 0.2, 0.9) and two or more cola drinks/day (OR = 0.6, 95% CI: 0.3, 1.4). The associations for tea and cola drinks were not confounded by smoking or coffee consumption.


PESI score for predicting clinical outcomes in PE patients with right ventricular involvement.
Pulmonary embolism (PE) patients with right ventricular (RV) involvement are a heterogenous group who mandate further risk stratification. Our objective was to evaluate the efficacy of the PE severity index (PESI) for predicting adverse clinical outcomes among PE patients with RV involvement. Consecutive normotensive PE patients with RV involvement were allocated according to admission PESI score (PESI ≤ III vs. PESI ≥ IV). The primary outcome included hemodynamic instability and in-hospital mortality. Secondary outcomes included each component of the primary outcome as well as mechanical ventilation, thrombolytic therapy, acute kidney injury, and major bleeding. Multivariable logistic regression model was performed to assess the independent association between the PESI score and primary outcome. C-Statistic was used to compare the PESI with the BOVA score. A total of 253 patients were evaluated: 95 (38%) with a PESI ≥ IV. Of them, 82 (32%) patients were classified as intermediate-low risk and 171 (68%) as intermediate-high risk. Fifty (20%) patients had at least 1 adverse event. Multivariate analysis demonstrated the PESI to be an independent predictor for the primary outcome (HR 4.81, CI 95%, 1.15-20.09, p = 0.031), which was increased with a concomitant increase of the PESI score (PESI I 4.2%, PESI II 3.4%, PESI III 12%, PESI IV 16.3%, PESI V 23.1%, p for trend < 0.001). C-Statistic analysis for the PESI score yielded an AUC-0.746 (0.637-0.854), p = 0.001, compared to the BOVA score: AUC-0.679 (0.584-0.775), p = 0.011. PESI score was found to predict adverse outcomes among normotensive PE patients with RV involvement.


Up-regulation of activating transcription factor-5 suppresses SAP expression to activate T cells in hemophagocytic syndrome associated with Epstein-Barr virus infection and immune disorders.
Hemophagocytic syndrome (HPS) is a fatal, pro-inflammatory cytokine disorder that is associated with viral infections and immune disorders. Previously, we demonstrated that Epstein-Barr virus latent membrane protein-1 (LMP-1) could down-regulate the SAP gene, enhancing Th1 cytokine secretion in T cells and leading to HPS. The exact mechanism of SAP gene regulation by LMP-1 remains to be clarified. In this study, using cDNA microarray analysis, we identified ATF5 as the candidate transcriptional repressor for SAP expression in LMP-1-expressing T cells. LMP-1 up-regulated ATF5 via TRAF2,5/NF-kappaB signals to suppress SAP gene expression. Reporter assays and electrophoretic mobility shift assays revealed that ATF5 bound differentially to two sites of the SAP promoter. In resting T cells, ATF5 bound predominantly to the high-affinity site in the -81 to -74 region while additionally binding to the low-affinity site at -305 to -296 in LMP-1-expressing T cells. Such binding subsequently disrupted the transcription of the SAP gene. At the same time, Th1 cytokine secretion was enhanced. This phenomenon was also observed in conditions such as ATF5 overexpression, phytohemagglutinin stimulation of primary T cells, and ligand engagement of T-cell lines. Therefore, the down-regulation of the SAP gene by ATF5 may represent a common mechanism for the pathogenesis of HPS that is associated with either Epstein-Barr virus infection or immune disorders with dysregulated T-cell activation.