Development of 12 sets of chromosome segment substitution lines that enhance allele mining in Asian cultivated rice.
Many agronomic traits that are important in rice breeding are controlled by multiple genes. The extensive time and effort devoted so far to identifying and selecting such genes are still not enough to target multiple agronomic traits in practical breeding in Japan because of a lack of suitable plant materials in which to efficiently detect and validate beneficial alleles from diverse genetic resources. To facilitate the comprehensive analysis of genetic variation in agronomic traits among Asian cultivated rice, we developed 12 sets of chromosome segment substitution lines (CSSLs) with the japonica background, 11 of them in the same genetic background, using donors representing the genetic diversity of Asian cultivated rice. Using these materials, we overviewed the chromosomal locations of 1079 putative QTLs for seven agronomic traits and their allelic distribution in Asian cultivated rice through multiple linear regression analysis. The CSSLs will allow the effects of putative QTLs in the highly homogeneous japonica background to be validated.


Self-assembly of an imidazolate-bridged Fe(III)/Cu(II) heterometallic cage.
A rare, discrete, mixed-valent, heterometallic Fe(III)/Cu(II) cage, [Cu6Fe8L8](ClO4)12·χsolvent (H3L = tris{[2-{(imidazole-4-yl)methylidene}amino]ethyl}amine), was designed and synthesized via metal-ion-directed self-assembly with neutral tripodal metalloligands. The formation of this coordination cage was demonstrated by X-ray crystallography, ESI mass spectrometry, FT-IR, and UV-vis-NIR spectroscopy.


Does age modify the association between physical work demands and deterioration of self-rated general health?
Objective Due to the growing proportion of older employees in the work force in several countries, the importance of age in the association between work and health is becoming increasingly relevant. Few studies have investigated whether age modifies the association of physical work demands with health. We hypothesized that the association of demanding body postures with deteriorated self-rated health (SRH) is stronger among older employees than among younger employees. Method We analyzed three 5-year cohorts in the Danish Work Environment Cohort Study comprising 8318 observations from 5204 employees (follow-up participation rate 83%) with good baseline SRH. Physical work demands were assessed as demanding body postures. Age was divided into tertiles; young (18-32 years), middle-aged (33-43 years) and old (44-59 among men and 44-54 years among women). Poor SRH ("fairly good", "poor", and "very poor") was measured with a single item. Log binomial regressions were stratified by gender. Effect modification (ie, interaction) was defined as deviation from additivity and examined by calculating the relative excess risk due to interaction (RERI). The reference group was employees aged 18-32 years with low physical exposure. Results When predicting deterioration of SRH, an interaction between demanding body postures and age was found among men [RERI: 0.75, 95% confidence interval (95% CI) 0.16-1.34, regarding the age group 44-59 years] and among women (RERI: 0.84, 95% CI 0.19-1.34, for the age group 33-43 years; and 1.17, 95% CI 0.42-1.93, for the age group 44-54 years). Conclusion The study findings suggest that demanding body postures have a stronger impact on health among older compared to younger employees.


The Smallest Diplodocid Skull Reveals Cranial Ontogeny and Growth-Related Dietary Changes in the Largest Dinosaurs.
Sauropod dinosaurs were the largest terrestrial vertebrates; yet despite a robust global fossil record, the paucity of cranial remains complicates attempts to understand their paleobiology. An assemblage of small diplodocid sauropods from the Upper Jurassic Morrison Formation of Montana, USA, has produced the smallest diplodocid skull yet discovered. The ~24 cm long skull is referred to cf. Diplodocus based on the presence of several cranial and vertebral characters. This specimen enhances known features of early diplodocid ontogeny including a short snout with narrow-crowned teeth limited to the anterior portion of the jaws and more spatulate teeth posteriorly. The combination of size plus basal and derived character expression seen here further emphasizes caution when naming new taxa displaying the same, as these may be indicative of immaturity. This young diplodocid reveals that cranial modifications occurred throughout growth, providing evidence for ontogenetic dietary partitioning and recapitulation of ancestral morphologies.


Care of Infectious Conditions in an Observation Unit.
Infectious conditions such as skin and soft tissue infections (SSTIs), Urogenital infections and peritonsillar abscesses frequently require care beyond emergency stabilization and are well-suited for short term care in an observation unit. SSTIs are a growing problem, partly due to emergence of strains of methicillin-resistant S. aureus (MRSA). Antibiotic choice is guided by the presence of purulence and site of infection. Purulent cellulitis is much more likely to be associated with MRSA. Radiographic imaging should be considered to aid in management in patients who are immunosuppressed, have persistent symptoms despite antibiotic therapy, recurrent infections, sepsis or diabetes.


Locally delivered doxycycline improves the healing following non-surgical periodontal therapy in smokers.
The outcome of non-surgical periodontal therapy is known to be inferior in smokers compared to non-smokers. In the present study, the question was asked whether such a difference in healing response may be less evident following adjunctive use of locally delivered controlled-release doxycycline. One hundred and three patients (42 smokers, 61 non-smokers), each having at least eight periodontal sites with PPD (probing pocket depth) > or =5 mm, were following stratification for smoking randomly assigned to two different treatment protocols; non-surgical scaling/root planing (Control) or ultrasonic instrumentation+application of a 8.5% w/w doxycycline gel (Atridox trade mark ) (Test). Instructions in oral hygiene were given to all patients. Clinical examinations of plaque, PPD, clinical attachment level (CAL) and bleeding following pocket probing were performed at baseline and after 3 months. Primary efficacy endpoints were changes in PPD and CAL. Patient mean values were calculated as basis for statistical analysis (multiple regression analyses). The baseline examination revealed no significant difference in mean PPD between treatment groups or between smokers and non-smokers (mean PPD 5.7-5.9 mm). The mean PPD reduction in the control group at 3-month was 1.1 mm (SD=0.45) for smokers and 1.5 mm (0.67) for non-smokers. In the test group the PPD reduction was 1.4 mm (0.60) and 1.6 mm (0.45) for smokers and non-smokers, respectively. The mean CAL gain for smokers and non-smokers amounted to 0.5 mm (0.56) and 0.8 mm (0.71), respectively, in the control group, and to 0.8 mm (0.72) and 0.9 mm (0.82), respectively, in the test group. Multiple regression analysis revealed that smoking and initial PPD negatively influenced the treatment outcome in terms of PPD reduction and CAL gain, while the use of doxycycline had a significant positive effect. Locally applied controlled-release doxycycline gel may partly counteract the negative effect of smoking on periodontal healing following non-surgical therapy.


Comparison of alternative modelling techniques in estimating short-term effect of air pollution with application to the Italian meta-analysis data (MISA Study).
In 2002, serious criticism was raised about the use of standard statistical software (Splus, SAS, Stata) to fit Generalized Additive Models (GAM) to epidemiological time series data. This criticism concerns convergence problems of the backfitting algorithm and inappropriate use of a linear approximation in estimating standard errors of estimates for parametric terms, such as the effect of air pollution. Here we analysed the association between PM10 and Mortality/Hospital Admissions in the Italian Meta-analysis of Short-term effects of Air pollutants (MISA) using two alternative approaches that are not affected by the same drawbacks: GAM with penalized regression spline fitted by the direct method in R (GAM-R) software and Generalized Linear Models with natural cubic spline (GLM+NS). A sensitivity analysis is also provided varying number of degrees of freedom for the seasonality spline and modality of adjustment for confounding effect of temperature. Published theoretical results and a simulation study are provided in order to explain discrepancies between GLM+NS and GAM-R estimates. We conclude that in general the fully parametric GLM+NS approach retains better statistical properties than GAM-R that could bring to biased air pollution effect estimates unless a certain degree of under-smoothing for seasonality spline is settled.


Current advances in the treatment of adolescent drug use.
Research on the development and efficacy of drug abuse treatment for adolescents has made great strides recently. Several distinct models have been studied, and these approaches range from brief interventions to intensive treatments. This paper has three primary aims: to provide an overview of conceptual issues relevant to treating adolescents suspected of drug-related problems, including an overview of factors believed to contribute to a substance use disorder, to review the empirical treatment outcome literature, and to identify areas of need and promising directions for future research.


[Morphological verification problems of Chernobyl factor influence on the testis of coal miners of Donbas-liquidators of Chernobyl accident].
Problem of a diagnostic of Chernobyl factor influences on different organs and systems of Chernobyl accident liquidators are remain actually until now. Though morbidly background which development at unfavorable work conditions in underground coalminers prevents from objective identification features of Chernobyl factor influences. The qualitative and quantitative histological and immunohistochemical law of morphogenesis changes in testis of Donbas's coalminer - non-liquidators Chernobyl accident in comparison with the group of Donbas's coalminers-liquidators Chernobyl accident, which we were stationed non determined problem. This reason stipulates to development and practical use of mathematical model of morphogenesis of a testis changes.


Poly(ester amine) synthesized from trimethylolpropane triacrylate and spermine as an efficient siRNA carrier.
Small interfering RNA (siRNA) is a promising candidate for gene therapy due to the strong and specific gene silencing effects. However, to effectively silence any protein, lack of an efficient delivery system is major obstacle for siRNA therapeutics. In the present study, we report on the development of a novel poly(ester amine) (PEA) as an efficient siRNA carrier. The PEA was prepared by a Michael addition reaction between trimethylolpropane triacrylate (TT) and spermine (SPE). The composition of the PEA was characterized by 1H nuclear magnetic resonance (1H NMR) and the molecular weight was measured using gel permeability chromatography (GPC). This TT-SPE effectively condensed siRNA into a compact nanoscale structure (size: 76 nm) with homogenous size distribution and provided superior protection of siRNA from RNase A enzyme. Furthermore, TT-SPE/ siRNA complexes showed good intracellular uptake and had efficacious gene silencing effect with low toxicity compared to PEI 25K. These findings demonstrated that TT-SPE has potential as an alternative to PEI 25K for siRNA-based gene therapy.


Photosynthetic responses to salinity in two clones of Agrostis stolonifera.
The response of photosynthesis, Fe , to salinity was examined in two clones of Agrostis stolonifera, one derived from a salt marsh (SM) and the other from an inland site (IL). The response of young and old leaves was examined over one week of salt treatment and changes in leaf water relations and concentrations of Na+ , Cl- and K+ ions were also monitored. Sodium+ and chloride- concentrations rose much more sharply in the older leaves of both clones and Fe declined to ca. zero by Day 4. Fe in the young leaves of the SM clone was unaffected by salt whilst the young leaves of the IL clone showed a 20% reduction in Fe within 24 h of salt application. This decline was due to a decline in stomatal conductance and a reduction in the photosynthetic capacity of the mesophyll and was associated with a greater accumulation of Na+ and Cl- ions and loss of K+ ions than in the SM clone. The significance of the salt exclusion from the young leaves of the SM clone to its growth on the salt marsh is discussed.


The evolution of omentum transposition: from lymphedema to spinal cord, stroke and Alzheimer's disease.
It is now well established that the omentum incorporates into its tissues a variety of biological factors that exert a favorable effect on the central nervous system. Physiological characteristics of the omentum include edema absorption, fibrotic inhibition, blood-brain barrier penetration and, of major importance, angiogenic activity. Over several decades, studies have shown increasing clinical uses of the omentum following its placement on various structures within the body. This paper details the evolution of omental transposition (OT) up to the present at which time OT is being applied to the brain of Alzheimer disease (AD) patients. Success in this area raises the possibility that the omentum may prove to be a present-day treatment for patients with AD until future pharmaceutical and/or genetic forms of treatment are developed.


Proteolytic enzyme activities in rat peritoneal exudate.
Proteinase activities in rat thioglycollate elicited peritoneal cells and the cell-free supernatant (lavage fluid) were measured by using the following substrates: Suc-Ala-Ala-Pro-Phe-Methyl-Coumarin-Amide (for cathepsin G or chymase), Suc-Ala-Ala-Ala-AMC (for elastase or elastase-like), Z-Arg-Arg-AMC (for cathepsin B), haemoglobin (for cathepsin D) and Ala-AMC (for alanine-aminopeptidase: AAP). The enzyme activities were correlated to the quantitative distribution of various cell types in the exudate from 0 to 192 nd h. In the supernatant all the examined activities showed a higher value at 72nd h. In the cells activity of chymase and AAP proved to be very high at 0 h but after four h the activities were dropped. From this time all enzyme activities started to elevate till the 24th h. At the 96th h only the activity of cathepsin B and AAP had a high value. We conclude that the intracellular activation and secretion of proteolytic enzymes characteristic for the various peritoneal cell types involved in the acute and chronic inflammatory reaction can be followed by activity measurements using enzyme-specific substrates and inhibitors.


Caroticoclinoid Bar: A Systematic Review and Meta-Analysis of Its Prevalence and Potential Implications in Cerebrovascular and Skull Base Surgery.
The presence of a caroticoclinoid bar (CCB) has been implicated in both transcranial and endonasal surgery. Its morphology reflects differences in the microsurgical anatomy of the parasellar area and its manipulation during anterior or middle clinoidectomy can result in internal carotid artery injury. Although adjustment of the surgical technique according to the CCB anatomic variants is required for safe surgical access to the paraclinoid region, a review indicated the lack of a systematic assortment of reported data regarding the prevalence of the CCB. Thus, our objective was to systematically review and document the prevalence of the CCB and its anatomic variations. Three databases were systematically reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement through August 2018 to identify relevant studies. A total of 27 reports (7521 subjects or specimens, 14,449 sides) were included in the present meta-analysis. The overall pooled prevalence of the CCB was 32.6% (95% confidence interval [CI], 26.6%-38.8%) when measured in the subjects or specimens and 23.6% (95% CI, 19.7%-27.6%) when measured in each side. The overall prevalence of the CCB reported from imaging studies was 23.1% (95% CI, 8.9%-41.4%) for the subjects/specimens and 18.7% (95% CI, 12.6%-25.7%) for each side. The presence of the CCB was slightly more prevalent (P = 0.050) on the right side. Our results showed a considerable prevalence of the CCB, with lower prevalence rates found among imaging studies. Although meticulous preoperative investigation is mandatory, surgeons treating patients with parasellar pathologic entities should always be vigilant regarding the CCB.


Homodimeric structure and double-stranded RNA cleavage activity of the C-terminal RNase III domain of human dicer.
Human Dicer contains two RNase III domains (RNase IIIa and RNase IIIb) that are responsible for the production of short interfering RNAs and microRNAs. These small RNAs induce gene silencing known as RNA interference. Here, we report the crystal structure of the C-terminal RNase III domain (RNase IIIb) of human Dicer at 2.0 A resolution. The structure revealed that the RNase IIIb domain can form a tightly associated homodimer, which is similar to the dimers of the bacterial RNase III domains and the two RNase III domains of Giardia Dicer. Biochemical analysis showed that the RNase IIIb homodimer can cleave double-stranded RNAs (dsRNAs), and generate short dsRNAs with 2 nt 3' overhang, which is characteristic of RNase III products. The RNase IIIb domain contained two magnesium ions per monomer around the active site. The distance between two Mg-1 ions is approximately 20.6 A, almost identical with those observed in bacterial RNase III enzymes and Giardia Dicer, while the locations of two Mg-2 ions were not conserved at all. We presume that Mg-1 ions act as catalysts for dsRNA cleavage, while Mg-2 ions are involved in RNA binding.


Biophysical characterization of Vpu from HIV-1 suggests a channel-pore dualism.
Vpu from HIV-1 is an 81 amino acid type I integral membrane protein which consists of a cytoplasmic and a transmembrane (TM) domain. The TM domain is known to alter membrane permeability for ions and substrates when inserted into artificial membranes. Peptides corresponding to the TM domain of Vpu (Vpu(1-32)) and mutant peptides (Vpu(1-32)-W23L, Vpu(1-32)-R31V, Vpu(1-32)-S24L) have been synthesized and reconstituted into artificial lipid bilayers. All peptides show channel activity with a main conductance level of around 20 pS. Vpu(1-32)-W23L has a considerable flickering pattern in the recordings and longer open times than Vpu(1-32). Whilst recordings for Vpu(1-32)-R31V are almost indistinguishable from those of the WT peptide, recordings for Vpu(1-32)-S24L do not exhibit any noticeable channel activity. Recordings of WT peptide and Vpu(1-32)-W23L indicate Michaelis-Menten behavior when the salt concentration is increased. Both peptide channels follow the Eisenman series I, indicative for a weak ion channel with almost pore like characteristics.


Awareness of children's developmental problems and sharing of concerns with parents by preschool teachers and childcare workers: The Japanese context.
This study aims to determine the extent to which preschool teachers and childcare workers are aware of the presence of developmental problems among children and to what extent they share information with parents about their concerns regarding a child's development or diagnosis of neurodevelopmental disorders (NDDs). We wrote to all 924 preschools and childcare centres in Japan's Nagano and Yamanashi prefectures to request participants. We then sent survey forms to the preschools and childcare centres that agreed to cooperate for three grades comprising 3-, 4- and 5-year-olds in the school year 2020. We asked the staff member in charge of each child to complete the survey. The survey included questions about the teacher's concerns regarding the possibility of an NDD and whether the matter had been shared with the children's parents. We obtained data for 10 354 children from 206 preschools and childcare centres (response rate = 22.3%). Among these children, 457 (4.4%) had an NDD diagnosis that their parents shared with the teachers. However, the teachers of 1274 children (12.3%) had concerns regarding their development but were not informed by the parents about the diagnosis, if any. These 1274 children included 775 (60.8%) cases where the teachers failed to share their concerns with parents because (1) the teachers could not communicate with parents (n = 119), (2) the teachers were not sure if there was a neurodevelopmental problem (n = 360) and (3) the parents were not aware of the problem (n = 296). Preschool teachers and childcare workers had concerns about the development of a substantial proportion of children in their charge. However, teachers and childcare workers did not share their concerns regarding many children's developmental problems with their parents. The findings suggest that there are challenges in information-sharing between teachers/childcare workers and parents.


Parents' representations of their children: an exploratory study using the Osgood Semantic Differential Scales.
The results of an exploratory national study carried out in Italy using Osgood's Semantic Differential Scales (Osgood, Suci, & Tannenbaum, 1957) with parents of 100 normal 6- to 11-yr.-old children in mainstream classrooms are reported. The aim was to devise a simple tool to be used to explore parents' perceptions of their children in this age group. Parents were asked to rate "my child" using some of Osgood's Semantic Differential Scales especially adapted for this study. Participants were 97 fathers and 100 mothers. Fathers were 32 to 57 years of age (M = 43.2, SD = 5.4), mothers were 29 to 49 years of age (M = 39.7, SD =4.4). In factor analysis four factors were identified: Activity, Evaluation, Emotions evoked by the child, Personality/Physical contact. Average factor scores were significantly different. There were no significant differences between fathers and mothers on the four factor scores. Children were more positively evaluated the younger they were.


Methylglyoxal inhibition of cytosolic ascorbate peroxidase from Nicotiana tabacum.
Methylglyoxal (MG) is one of the aldehydes accumulated in plants under environmental stress. Cytosolic ascorbate peroxidase (cAPX) plays a key role in the protection of cells from oxidative damage by scavenging reactive oxygen species in higher plants. A cDNA encoding cAPX, named NtcAPX, was isolated from Nicotiana tabacum. We characterized recombinant NtcAPX (rNtcAPX) as a fusion protein with glutathione S-transferase to investigate the effects of MG on APX. NtcAPX consists of 250 amino acids and has a deduced molecular mass of 27.5 kDa. The rNtcAPX showed a higher APX activity. MG treatments resulted in a reduction of APX activity and modifications of amino groups in rNtcAPX with increasing K(m) for ascorbate. On the contrary, neither NaCl nor cadmium reduced the activity of APX. The present study suggests that inhibition of APX is in part due to the modification of amino acids by MG.


Do CD4+ CD25+ immunoregulatory T cells hinder tumor immunotherapy?
After years of banishment from mainstream immunology, the notion that one subset of T cells can exert regulatory effects on other T lymphocytes is back in fashion. Recent work in knockout and transgenic mice has begun to bring molecular definition to our understanding of immunoregulatory CD4+CD25+ T cells (Treg/Th3/Tr1). The identification of the glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18) expressed on T regulatory cells might afford new therapeutic opportunities. Another possible therapeutic intervention could be the blockade of signaling through the molecular pair of tumor necrosis factor-related activation induced cytokine (TRANCE) and receptor activator of NF-kappaB (RANK). Based on the available evidence from experimental mouse tumor models, however, it seems that simply blocking or even eliminating T regulatory function will not be enough to manage established tumors. The challenge for immunotherapists now is to overcome immunosuppression using the knowledge gained through the understanding of T regulatory cell function.


S2Snet: deep learning for low molecular weight RNA identification with nanopore.
Ribonucleic acid (RNA) is a pivotal nucleic acid that plays a crucial role in regulating many biological activities. Recently, one study utilized a machine learning algorithm to automatically classify RNA structural events generated by a Mycobacterium smegmatis porin A nanopore trap. Although it can achieve desirable classification results, compared with deep learning (DL) methods, this classic machine learning requires domain knowledge to manually extract features, which is sophisticated, labor-intensive and time-consuming. Meanwhile, the generated original RNA structural events are not strictly equal in length, which is incompatible with the input requirements of DL models. To alleviate this issue, we propose a sequence-to-sequence (S2S) module that transforms the unequal length sequence (UELS) to the equal length sequence. Furthermore, to automatically extract features from the RNA structural events, we propose a sequence-to-sequence neural network based on DL. In addition, we add an attention mechanism to capture vital information for classification, such as dwell time and blockage amplitude. Through quantitative and qualitative analysis, the experimental results have achieved about a 2% performance increase (accuracy) compared to the previous method. The proposed method can also be applied to other nanopore platforms, such as the famous Oxford nanopore. It is worth noting that the proposed method is not only aimed at pursuing state-of-the-art performance but also provides an overall idea to process nanopore data with UELS.


Fragility non-hip fracture patients are at risk.
Fragility fractures are a growing worldwide health care problem. Hip fractures have been clearly associated with poor outcomes. Fragility fractures of other bones are common reasons for hospital admission and short-term disability, but specific long-term outcome studies of non-hip fragility fractures are rare. The aim of our trial was to evaluate the 1-year outcomes of non-hip fragility fracture patients. This study is a retrospective cohort review of 307 consecutive older inpatient non-hip fracture patients. Patient data for analysis included fracture location, comorbidity prevalence, pre-fracture functional status, osteoporosis treatments and sociodemographic characteristics. The main outcomes evaluated were 1-year mortality and post-fracture functional status. As compared to the expected mortality, the observed 1-year mortality was increased in the study group (17.6 vs. 12.2 %, P = 0.005). After logistic regression, three variables remained as independent risk factors for 1-year mortality among non-hip fracture patients: malnutrition (OR 3.3, CI 1.5-7.1), Charlson comorbidity index (CCI) (OR 1.3, CI 1.1-1.5) and the Parker Mobility Score (PMS) (OR 0.85, CI 0.74-0.98). CCI and PMS were independent risk factors for a high grade of dependency after 1 year. Management of osteoporosis did not significantly improve after hospitalization due to a non-hip fragility fracture. The outcomes of older non-hip fracture patients are comparable to the poor outcomes of older hip fracture patients, and appear to be primarily related to comorbidities, pre-fracture function and nutritional status. The low rate of patients on osteoporosis medications likely reflects the insufficient recognition of the importance of osteoporosis assessment and treatment in non-hip fracture patients. Increased clinical and academic attention to non-hip fracture patients is needed.


Quantitative polymerase chain reaction analysis of serpiginous choroiditis with biopsy-proven testicular tuberculosis.
We report a case of a 47-year-old male patient presenting with diminution of vision in the left eye. The left eye fundus showed yellowish lesions with indistinct geographical margin extending over the posterior pole just abutting the macula, suggestive of diffuse choroiditis. The patient gave a history of testicular swelling for the past 2 years. Aqueous tap for polymerase chain reaction analysis was positive for IS6110 mycobacterial tuberculosis (TB) genome, and a biopsy of testicular sac was suggestive of tubercular epididymitis. A diagnosis of TB-multifocal serpiginoid choroiditis was established and was managed with anti-tubercular therapy and systemic steroids.


Controlling Aedes albopictus and Culex pipiens pallens using silver nanoparticles synthesized from aqueous extract of Cassia fistula fruit pulp and its mode of action.
Mosquitoes act as key vector for transmission of devastating parasites and pathogens which affect millions of people globally. In this research, the green synthesis of silver nanoparticles of Cassia fistula fruit pulp as an innovative and operative tool against vector mosquitoes is presented. Silver nanoparticles were characterized by a series of techniques including Fourier transform infrared spectroscopy, Transmission Electron Microscope and confirmed by Scanning Electron Microscope, UV-Vis spectrophotometry and X-ray diffraction. Silver nanoparticles were highly effective against the larvae (I-IV instar) and pupae of Aedes albopictus and Culex pipiens pallens after 24, 48 and 72 h of treatment. Ae. albopictus had LC50 values ranging from 8.3 mg/L (I instar) to 17.3 mg/L (pupae) and LC50 ranging from 1.1 mg/L (I instar) to 19.0 mg/L (pupae) against Cx. pipiens pallens. The systemic effect of AgNPs was further assessed in the fourth instar larvae of Ae. albopictus and Cx. pipiens pallens by measuring the levels of total proteins and activity of two important marker enzymes: Acetylcholinesterase and α- and β-carboxylesterase. Overall, the findings of the study suggest that the use of Cassia fistula-fruit pulp extract mediated synthesis of silver nanoparticles can be used for controlling vector mosquitoes. This is the first report on the mosquito larvicidal and pupicidal activity of AgNPs synthesized by Cassia fistula fruit pulp and its possible mechanism of action.


Role of Defects and Surface States in the Carrier Transport and Nonlinearity of the Diode Characteristics in PbS/ZnO Quantum Dot Solar Cells.
The roles of bulk surface states and interfacial defects are probed experimentally using a combination of current-voltage, capacitance-voltage, and impedance measurements. The critical importance of the quality of both the film and interfaces is evident in current-voltage measurements where shunting and interface states result in large dark currents and the subsequent loss of Jsc. These properties are shown to be critically related to the nature and role of the PbS QD interface with the (nominally) ohmic gold contact. Specifically, the nonideality of this interface results in the formation of an electric field and therefore a Schottky barrier that opposes the transport of carriers across the conventional ZnO-PbS CQD system. Nonidealities in the structure and absorber layer are also reflected in nonmonotonic behavior and dispersion in C-V measurements with trapping processes on the CQD surfaces, and the ZnO/PbS and PbS/Au interfaces also affecting the carrier dynamics, which is reflected in the response time of these systems under different biases.


The role of biosensors in the detection of emerging infectious diseases.
Global biosecurity threats such as the spread of emerging infectious diseases (i.e., avian influenza, SARS, Hendra, Nipah, etc.) and bioterrorism have generated significant interest in recent years. There is considerable effort directed towards understanding and negating the proliferation of infectious diseases. Biosensors are an attractive tool which have the potential to detect the outbreak of a virus and/or disease. Although there is a host of technologies available, either commercially or in the scientific literature, the development of biosensors for the detection of emerging infectious diseases (EIDs) is still in its infancy. There is no doubt that the glucose biosensor, the gene chip, the protein chip, etc. have all played and are still playing a significant role in monitoring various biomolecules. Can biosensors play an important role for the detection of emerging infectious diseases? What does the future hold and which biosensor technology platform is suitable for the real-time detection of infectious diseases? These and many other questions will be addressed in this review. The purpose of this review is to present an overview of biosensors particularly in relation to EIDs. It provides a synopsis of the various types of biosensor technologies that have been used to detect EIDs, and describes some of the technologies behind them in terms of transduction and bioreceptor principles.


Brain-specific angiogenesis inhibitor 2 (BAI2) may be activated by proteolytic processing.
Brain-specific angiogenesis inhibitor 2 (BAI2) is a member of adhesion-G protein-coupled receptors (GPCRs). BAI2 is dominantly expressed in the brain and its physiological ligands and functions are still unclear. Adhesion-GPCRs, including BAI2, commonly have a long N-terminal extracellular region (ECR) containing the GPCR proteolysis site (GPS) and the cleavage of the ECR at the GPS domain is suspected to be important for their function. In this study, we analyzed the proteolytic processing of BAI2 and its activation mechanism. Several cleaved C-terminal fragments of BAI2 were identified in mouse hippocampus. We confirmed that mutation in the GPS domain caused inhibition of the proteolysis of BAI2, which indicated the possibility that BAI2 was cleaved at the GPS domain. The association of the ECR putatively cleaved at the GPS domain and the C-terminal seven-transmembrane (7TM) fragment was detected by co-immunoprecipitation. We also found that furin prohormone convertase cleaved BAI2 at another site in the ECR. Additionally, the C-terminal fragment cleaved at the GPS domain specifically activated the nuclear factor of activated T-cells (NFAT) pathway. These results suggest that BAI2 is a functional GPCR regulated by proteolytic processing and activates the NFAT pathway.


Effect of multiplicative noise on least-squares parameter estimation with applications to the atomic force microscope.
Measurement of the power spectral density of (stochastic) Brownian fluctuations of micro- and nano-devices is used frequently to gain insight into their mechanistic properties. Noise is always present in these measurements and can directly influence any parameter estimation obtained through a least-squares analysis. Importantly, measurements of the spectral density of stationary random signals, such as Brownian motion, inherently contain multiplicative noise. In this article, we theoretically analyze the impact of multiplicative noise on fit parameters extracted using a least-squares analysis. A general analysis is presented that is valid for any fit function with any number of fit parameters. This yields closed-form expressions for the expected value and variance in the fit parameters and provides a rigorous theoretical framework for a priori determination of the effect of measurement uncertainty. The theory is demonstrated and validated through Monte Carlo simulation of synthetic data and by comparison to power spectral density measurements of the Brownian fluctuations of an atomic force microscope cantilever - analytical formulas for the uncertainty in the fitted resonant frequency and quality factor are presented. The results of this study demonstrate that precise measurements of fit parameters in the presence of noise are inherently problematic - individual measurements of the power spectral density are capable of yielding fit parameters that are many standard deviations away from the mean, with finite probability. This is of direct relevance to a host of applications in measurement science, including those connected with the atomic force microscope.


[Biofouling of heat exchange tubes].
We compared the biofouling behavior of different materials (admiralty brass, stainless steel, and titanium) commonly used to construct heat exchangers in thermoelectric plants. The incidence of film formation on the loss of heat during transference was assessed, and analyzed in terms of plant efficiency and corrosion, both general and localized development. Our results showed that the resistance of titanium and stainless steel to corrosion was similar, and much better than that of admiralty brass. Biofouling, however, was higher in the first two materials.


Type 1 and type 2 cytokine-mediated immune orchestration in the tumour microenvironment and their therapeutic potential.
Cancer remains the second leading cause of death worldwide despite modern breakthroughs in medicine, and novel treatments are urgently needed. The revolutionary success of immune checkpoint inhibitors in the past decade serves as proof of concept that the immune system can be effectively harnessed to treat cancer. Cytokines are small signalling proteins with critical roles in orchestrating the immune response and have become an attractive target for immunotherapy. Type 1 immune cytokines, including interferon γ (IFNγ), interleukin-12 (IL-12), and tumour necrosis factor α (TNFα), have been shown to have largely tumour suppressive roles in part through orchestrating anti-tumour immune responses mediated by natural killer (NK) cells, CD8+ T cells and T helper 1 (Th1) cells. Conversely, type 2 immunity involving group 2 innate lymphoid cells (ILC2s) and Th2 cells are involved in tissue regeneration and wound repair and are traditionally thought to have pro-tumoural effects. However, it is found that the classical type 2 immune cytokines IL-4, IL-5, IL-9, and IL-13 may have conflicting roles in cancer. Similarly, type 2 immunity-related cytokines IL-25 and IL-33 with recently characterised roles in cancer may either promote or suppress tumorigenesis in a context-dependent manner. Furthermore, type 1 cytokines IFNγ and TNFα have also been found to have pro-tumoural effects under certain circumstances, further complicating the overall picture. Therefore, the dichotomy of type 1 and type 2 cytokines inhibiting and promoting tumours respectively is not concrete, and attempts of utilising these for cancer immunotherapy must take into account all available evidence. This review provides an overview summarising the current understanding of type 1 and type 2 cytokines in tumour immunity and discusses the prospects of harnessing these for immunotherapy in light of previous and ongoing clinical trials.


Diffusion-weighted magnetic resonance imaging findings in a patient with cerebral syphilitic gumma.
Cerebral syphilitic gummas are rare entities, consisting of masses of granulation tissue that result from an exacerbated cell-mediated inflammatory response to Treponema pallidum, usually arising from the meninges of the convexity. Conventional magnetic resonance imaging and computed tomography findings of cerebral gummas have been reported, but diffusion-weighted imaging findings have not been previously described. In our patient, magnetic resonance imaging revealed a juxtacortical lesion with nodular enhancement, moderately restricted diffusion, a dural tail, and surrounding vasogenic edema. The role of diffusion-weighted imaging findings in the diagnosis of this condition is underscored.


Aphasia testing (auditory comprehension domain) using a new eye-tracking system in healthy participants.
Sakai R, Koike Y, Saito K, Matsunaga T, Shimada Y, Miyakoshi N. Aphasia testing (auditory comprehension domain) using a new eye-tracking system in healthy participants. Jpn J Compr Rehabil Sci 2022; 13: 31-35. We administered a conventional pointing-method test with eye-tracking to evaluate items associated with auditory comprehension and examined the concordance between the obtained results. The enrolled participants were 10 healthy volunteers. We performed tests after extracting auditory comprehension items from the SLTA, the WAB, and the Supplementary tests for the SLTA using the eye-tracking system and the pointing method. The mean test duration was 9 min 51 s ± 1 min 41 s (mean ± SD), and the percentage of correct answers was 100% and in perfect agreement for the pointing method and the eye-tracking system. The mean response time was 0.96 ± 0.36 s for the pointing method and -0.39 ± 0.21 s for the eye-tracking system. Hence, the latter was faster than the former, and examinees completed their responses before listening to the end of the questions. The new eye-tracking system makes it possible to perform aphasia tests (auditory comprehension items) comparable to the conventional pointing method.


Baseline serum HBV RNA is associated with the risk of hepatitis flare after stopping nucleoside analog therapy in HBeAg-negative participants.
HBV RNA in peripheral blood reflects HBV cccDNA transcriptional activity and may predict clinical outcomes. The prospective Melbourne HBV-STOP trial studied nucleot(s)ide analog discontinuation in HBeAg-negative non-cirrhotic participants with long-term virological suppression. Ninety-six weeks after stopping treatment, the proportion of participants with virological relapse (HBV DNA > 2000 IU/mL), biochemical relapse (ALT > 2 × ULN and HBV DNA > 2000 IU/mL), or hepatitis flare (ALT > 5 × ULN and HBV DNA > 2000 IU/mL) was 89%, 58%, and 38%, respectively. We evaluated the ability of serum HBV RNA levels to predict these outcomes. HBV RNA levels were measured using the Roche cobas 6800/8800 HBV RNA Investigational Assay. Sixty-five participants had baseline and longitudinal off-treatment specimens available for RNA testing. HBV RNA was detectable at baseline in 25% of participants and was associated with a higher risk of biochemical relapse (81% vs. 51%, p value 0.04) and hepatitis flare (63% vs. 31%, p value 0.04). Participants who had undetectable serum HBV RNA as well as HBsAg ≤ 100 IU/mL at baseline were less likely to experience virological relapse (4 of 9, 44%) than participants with detectable HBV RNA and HBsAg level > 100 IU/mL (15/15, 100%; p value 0.0009). Off-treatment levels of HBV RNA were correlated with HBV DNA and were associated with the risk of hepatitis flare. Serum HBV RNA may be a useful biomarker for guiding clinical decision-making before stopping nucleot(s)ide analog therapy. Baseline HBV RNA and HBsAg levels are associated with the risk of clinical relapse, hepatitis flare, and disease remission off-treatment.


Development, characterization, and skin delivery studies of related ultradeformable vesicles: transfersomes, ethosomes, and transethosomes.
Ultradeformable vesicles (UDV) have recently become a promising tool for the development of improved and innovative dermal and transdermal therapies. The aim of this work was to study three related UDV: transfersomes, ethosomes, and transethosomes for the incorporation of actives of distinct polarities, namely, vitamin E and caffeine, and to evaluate the effect of the carrier on skin permeation and penetration. These actives were incorporated in UDV formulations further characterized for vesicles imaging by transmission electron microscopy; mean vesicle size and polydispersity index by photon correlation spectroscopy; zeta potential by laser-Doppler anemometry; deformability by pressure-driven transport; and incorporation efficiency (IE) after actives quantification by high-performance liquid chromatography. Topical delivery studies were performed in order to compare UDV formulations regarding the release, skin permeation, and penetration profiles. All UDV formulations showed size values within the expected range, except transethosomes prepared by "transfersomal method", for which size was smaller than 100 nm in contrast to that obtained for vesicles prepared by "ethosomal method". Zeta potential was negative and higher for formulations containing sodium cholate. The IE was much higher for vitamin E- than caffeine-loaded UDV as expected. For flux measurements, the following order was obtained: transethosomes (TE) > ethosomes (E) ≥ transfersomes (T). This result was consistent with the release and skin penetration profiles for Vitamin E-loaded UDV. However, the releasing results were totally the opposite for caffeine-loaded UDV, which might be explained by the solubility and thermodynamic activity of this active in each formulation instead of the UDV deformability attending to the higher non-incorporated fraction of caffeine. Anyway, a high skin penetration and permeation for all caffeine-loaded UDV were obtained. Transethosomes were more deformable than ethosomes and transfersomes due to the presence of both ethanol and surfactant in their composition. All these UDV were suitable for a deeper skin penetration, especially transethosomes.


Communication and basic health counselling skills to tackle vaccine hesitancy.
The Italian law 119/2017 mandates ten childhood vaccinations to allow population aged 0-16 attend educational places and state school. This law enforcement is due to low coverage rates for some vaccine-preventable diseases and to a complex phenomenon known as vaccine hesitancy. Basic health counselling skills represent relevant resources to let healthcare workers effectively address vaccine hesitancy in the population. We indicated recommended communication approaches and basic health counselling skills to be applied by public health professionals according to the specific target population with vaccine deficit that means people not at all or partially reached by vaccinations. Public health professionals are called to know, acquire, use, and adapt basic health counselling skills to effectively address vaccine hesitancy diversely affecting different groups of population.


Adverse effects of antipsychotics on sleep in patients with schizophrenia. Systematic review and meta-analysis.
Our objective was to conduct a systematic review and meta-analysis of adverse effects on sleep in patients with schizophrenia receiving antipsychotic treatment. A systematic search was performed in PubMed, Cochrane Central, Embase, Toxline, Ebsco, Virtual Health Library, Web of Science, SpringerLink, and in Database of abstracts of Reviews of Effects of Randomized Clinical Trials to identify eligible studies published from January 1990 to October 2021. The methodological quality of the studies was evaluated using the CONSORT list, and the Cochrane bias tool. Network meta-analysis was performed using the Bayesian random-effects model, with multivariate meta-regression to assess the association of interest. 87 randomized clinical trials were identified that met the inclusion criteria, and 70 articles were included in the network meta-analysis. Regarding the methodological quality of the studies, 47 had a low or moderate bias risk. The most common adverse effects on sleep reported in the studies were insomnia, somnolence, and sedation. The results of the network meta-analysis showed that ziprasidone was associated with an increased risk of insomnia (OR, 1.56; 95% credible interval CrI, 1.18-2.06). Several of the included antipsychotics were associated with a significantly increased risk of somnolence; haloperidol (OR, 1.90; 95% CrI, 1.12-3.22), lurasidone (OR, 2.25; 95% CrI, 1.28-3.97) and ziprasidone (OR, 1.79; 95% CrI, 1.06-3.02) had the narrowest confidence intervals. In addition, perphenazine (OR, 5.33; 95% CrI, 1.92-14.83), haloperidol (OR, 2.61; 95% CrI, 1.14-5.99), and risperidone (OR, 2.41; 95% CrI, 1.21-4.80) were associated with an increased risk of sedation compared with placebo, and other antipsychotics did not differ. According to the SUCRAs for insomnia, chlorpromazine was ranked as the lowest risk of insomnia (57%), followed by clozapine (20%), while flupentixol (26 %) and perospirone (22.5%) were associated with a lower risk of somnolence. On the other hand, amisulpride (89.9%) was the safest option to reduce the risk of sedation. Insomnia, sedation, and somnolence were the most frequent adverse effects on sleep among the different antipsychotics administered. The evidence shows that chlorpromazine, clozapine, flupentixol, perospirone, and amisulpride had favorable safety profiles. In contrast, ziprasidone, perphenazine, haloperidol, and risperidone were the least safe for sleep. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017078052, identifier: PROSPERO 2017 CRD42017078052.


Responses of the desert green algae, Chlorella sp. to drought stress.
Desert algae are important components of the desert soil crust and play an essential role in desert soil ecosystem development. Owing to their special habitat, desert algae are often exposed to harsh environments, among which drought represents the most common stress. Green algae are considered to have drought tolerance potential; however, only a few studies have investigated this. In this study, we selected the green alga Chlorella sp., which was isolated from desert soil, and studied its physiological response to polyethylene glycol (PEG) 6000-induced drought stress. The results showed that drought stress can affect the photosynthetic efficiency of Chlorella sp., reduce its water retention ability, and destroy its ultrastructure. However, Chlorella sp. can cope with drought stress through a series of physiological regulatory strategies. Protective strategies include quick recovery of photosynthetic efficiency and increased chlorophyll content. In addition, induced synthesis of soluble proteins, lipids, and extracellular polysaccharide (EPS), and accumulation of osmotic regulatory substances, such as sucrose and trehalose, also contribute to improving drought tolerance in Chlorella sp. This study provides insights into the physiological responses of Chlorella sp. to drought stress, which may be valuable for understanding the underlying drought adaptation mechanisms of desert green algae.


Analytical and functional similarity of Amgen biosimilar ABP 215 to bevacizumab.
ABP 215 is a biosimilar product to bevacizumab. Bevacizumab acts by binding to vascular endothelial growth factor A, inhibiting endothelial cell proliferation and new blood vessel formation, thereby leading to tumor vasculature normalization. The ABP 215 analytical similarity assessment was designed to assess the structural and functional similarity of ABP 215 and bevacizumab sourced from both the United States (US) and the European Union (EU). Similarity assessment was also made between the US- and EU-sourced bevacizumab to assess the similarity between the two products. The physicochemical properties and structural similarity of ABP 215 and bevacizumab were characterized using sensitive state-of-the-art analytical techniques capable of detecting small differences in product attributes. ABP 215 has the same amino acid sequence and exhibits similar post-translational modification profiles compared to bevacizumab. The functional similarity assessment employed orthogonal assays designed to interrogate all expected biological activities, including those known to affect the mechanisms of action for ABP 215 and bevacizumab. More than 20 batches of bevacizumab (US) and bevacizumab (EU), and 13 batches of ABP 215 representing unique drug substance lots were assessed for similarity. The large dataset allows meaningful comparisons and garners confidence in the overall conclusion for the analytical similarity assessment of ABP 215 to both US- and EU-sourced bevacizumab. The structural and purity attributes, and biological properties of ABP 215 are demonstrated to be highly similar to those of bevacizumab.


In Vitro Tumor Mimetic Spheroid Model: Void Space within a Self-Detachable Cross-Linked Hydrogel.
The three-dimensional (3D) spheroid cell culture model is crucial in screening anticancer drugs in vitro and understanding tumor cell behavior. However, the current in vitro models require highly skilled techniques. Here, we present an in vitro, tumor-mimetic, self-detachable, cancer cell spheroid model that provides the confined space of a tumor microenvironment, convenient spheroid retrieval, immunostaining, treatment, and imaging. We formed a void space within alginate macrobeads by ionic disintegration at a specific region inside. The macrobeads were further destabilized with bovine serum albumin to retrieve the spheroid cultured within the void space. Quantitative analysis of the immunofluorescence images of the cultured spheroids showed enhanced expressions of the hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase-9 (CA-9), like monolayer cultures of cancer cells under hypoxic conditions (0.2% oxygen). Furthermore, adding CoCl2 to the cell culture media induces even higher amounts of HIF-1α and CA-9 in the cultured spheroids. In conclusion, the present work highlighted the in vitro spheroid model, which is closer to the tumor microenvironment and has user-friendly cell seeding, spheroid retrieval, and immunostaining steps.


Application of new imaging and calculation techniques to activity and dose assessment in the case of a 106Ru contaminated wound.
The aim of this paper is to describe the dosimetric evaluation of a point contamination that occurred in a laboratory during the examination of an irradiated sample. The incident led to point contamination of the operator's finger due to the presence of mainly 106Ru, with its progeny, 106Rh. The paper reports on the activity and dose assessment, performed using several methods. The measured activity was obtained using a conventional device based on a germanium detector and confirmed using software developed at IRSN, based on reconstruction of voxel phantom associated with the Monte Carlo N-Particle code (MCNP) for in vivo measurement. Two dose assessment calculations were performed using both analytical and Monte Carlo methods, applying the same approach as for activity assessment based on the personal computational phantom of the finger. The results are compared, followed by a discussion on the suitability of the tools described in this study.


Proteomic Profiling of Sugar Beet (Beta vulgaris) Leaves during Rhizomania Compatible Interactions.
Rhizomania, caused by Beet necrotic yellow vein virus (BNYVV), severely impacts sugar beet (Beta vulgaris) production throughout the world, and is widely prevalent in most production regions. Initial efforts to characterize proteome changes focused primarily on identifying putative host factors that elicit resistant interactions with BNYVV, but as resistance breaking strains become more prevalent, effective disease control strategies will require the application of novel methods based on better understanding of disease susceptibility and symptom development. Herein, proteomic profiling was conducted on susceptible sugar beet, infected with two strains of BNYVV, to clarify the types of proteins prevalent during compatible virus-host plant interactions. Total protein was extracted from sugar beet leaf tissue infected with BNYVV, quantified, and analyzed by mass spectrometry. A total of 203 proteins were confidently identified, with a predominance of proteins associated with photosynthesis and energy, metabolism, and response to stimulus. Many proteins identified in this study are typically associated with systemic acquired resistance and general plant defense responses. These results expand on relatively limited proteomic data available for sugar beet and provide the ground work for additional studies focused on understanding the interaction of BNYVV with sugar beet.


Establishment of accurate incidence rates for head and spinal cord injuries in developing and developed countries: a capture-recapture approach.
Prevention of head and spinal cord injuries is defined as a reduction in the incidence of these disabilities. Accurate incidence data are fundamental to any prevention program. The current approaches toward determining incidence rates for head and spinal cord injuries are summarized. Previous research has focused on passive surveillance systems and population-based registries. An alternative system for monitoring the incidence of head injuries is discussed that uses a surveillance methodology called capture-recapture. This method employs multiple population-based sources to identify cases and uses the cases that overlap between the sources to estimate the degree of undercount in the population. This estimate in turn is used to produce an ascertainment-corrected incidence estimate. Through the use of methods such as capture-recapture, accurate monitoring of the incidence of head and spinal injuries across developing and developed countries is indeed feasible.


Feasibility of using ultrasonic emission for clinical evaluation of prosthetic hips.
Previous acoustic emission (AE) studies of the hip have proposed using AE for the diagnosis of musculoskeletal conditions and assessing the clinical status (loosening, wear, etc.) of prostheses. However, these investigations have had problems with spurious signal noises or complicated measurement techniques, or both. We performed a study on 98 patients to evaluate the feasibility of employing ultrasonic emission (UE) to determine total hip arthroplasty (THA) status, using a simple, hand-held measurement system that has addressed some of the prior problems with hip AE studies. UE was recorded from both hips of study patients during walking and sitting activities. The patients had 79 metal-on-polyethylene implants, and at least 15 each with ceramic-on-polyethylene, ceramic-on-ceramic and metal-on-metal articulations; 10 young subjects without THA were similarly recorded as controls. Data were obtained from waveform analysis and standard UE signal parameters. Patient radiographs were evaluated for THA status, and wear measurements were made for metal-on-polyethylene articulations. There were distinct types of UE waveforms produced; one was typical of the control subjects as well as some patients. We did not find an apparent relationship among these waveform types and type of THA bearing, length of implantation or wear measurements in the metal on polyethylene bearings. Our results suggest that it may be possible to assess the status of THA by UE signals, but further studies are necessary to quantify this finding. The clinical relevance of this investigation is that a simple, in-office screening means for THA patients could indicate those patients who require closer follow-up and monitoring.


Migraine and cerebral blood flow in the general population.
Observations that migraine increases risk of cardiovascular disease and ischemic brain changes may suggest sustained vascular differences between migraineurs and controls. In a population-based setting, we compared cerebral blood flow between migraineurs in the attack-free period and controls. Between 2006 and 2008, 2642 participants, aged 45-65, from the Rotterdam Study completed a migraine questionnaire and had complete usable MRI data. Participants were classified into controls (N = 2033), probable migraine (N = 153), or migraine (N = 456). Using 2D phase contrast MRI, we performed a cross-sectional analysis of the effect of migraine on total cerebral blood flow (tCBF), parenchymal cerebral blood flow (pCBF), and blood flow in each intracranial arterial using linear regression. Additionally, we performed stratified analysis of subtypes of migraine. Compared with controls, migraineurs had higher pCBF (1.07 ml/min/100 ml, 95% CI 0.08; 2.05). In particular, migraineurs had significantly higher blood flow in the basilar artery (4.70 ml/min, 95% CI 0.77; 8.62). Migraineurs in the attack-free period have higher pCBF, particularly basilar artery flow, compared to controls, supporting the notion of sustained vascular differences between these groups outside of migraine attacks.


Comparison of Clinical, Radiographic, and Immunologic Inflammatory Parameters Around Dental Implants with Cement-Retained and Screw-Retained Restorations: A 5-Year Prospective Cohort Study in Men.
To compare bleeding on probing (BoP), probing depth (PD; ≥ 4 mm), radiographic (peri-implant crestal bone loss [CBL]), and immunologic inflammatory (interleukin-1beta [IL-1β] and matrix metalloproteinase-9 [MMP-9]) parameters around dental implants with cement-retained (CR) and screw-retained (SR) implant-supported crowns. Based on the mode of retention of the restoration, 51 patients were divided into two groups: Group 1, consisting of 26 single implants restored with CR crowns, and Group 2, consisting of 25 single implants restored with SR crowns. Peri-implant BoP, PD, and CBL were scored, and levels of IL-1β and MMP-9 in the peri-implant crevicular fluid (PICF) in both groups were measured in duplicate using enzyme-linked immunosorbent assay. Full-mouth mechanical debridement was performed biannually in both groups. Statistical analysis was performed using Kruskal-Wallis test with the significance level set at P < .05. The mean CBL among implants in groups 1 and 2 was 1.7 ± 0.5 mm and 1.7 ± 0.4 mm, respectively. There was no statistically significant difference in mean BoP, PD, and CBL among implants in both groups (P > .05). There was no statistically significant difference between groups 1 and 2 in the PICF levels of IL-1β (7.3 ± 0.5 and 7.2 ± 0.5, respectively) and MMP-9 (165 ± 9.4 and 182 ± 10.6, respectively) (P > .05). The mode of retention of implant-supported crowns does not appear to affect their clinical correlations with BoP, PD, CBL, and levels of IL-1β and MMP-9 in the PICF when zinc oxide eugenol cement is used.


Obtaining molecular and structural information from 13C-14N systems with 13C FIREMAT experiments.
The effect of dipolar coupling to 14N on 13C FIREMAT (five pi replicated magic angle turning) experiments is investigated. A method is developed for fitting the 13C FIREMAT FID employing the full theory to extract the 13C-14N dipolar and 13C chemical shift tensor information. The analysis requires prior knowledge of the electric field gradient (EFG) tensor at the 14N nucleus. In order to validate the method the analysis is done for the amino acids alpha-glycine, gamma-glycine, l-alanine, l-asparagine, and l-histidine on FIREMAT FIDs recorded at 13C frequencies of 50 and 100 MHz. The dipolar and chemical shift data obtained with this analysis are in very good agreement with the previous single-crystal 13C NMR results and neutron diffraction data on alpha-glycine, l-alanine, and l-asparagine. The values for gamma-glycine and l-histidine obtained with this new method are reported for the first time. The uncertainties in the EFG tensor on the resultant 13C chemical shift and dipolar tensor values are assessed.


[Study of stresses in the fractured mandible in man. Theoretical measurement and verification by extensometric gauges in situ].
The authors study the various possibilities for measuring the stresses which develop within the mandible under the effect of masticatory forces. Several methods are proposed:--calculation with the aid of mathematical models,---the use of extensometric gauges in vitro with the aid of traction machines,--the use of extensometric gauges in vivo. The results obtained with all three methods are in agreement and, in the opinion of the authors, provide experimental evidence of the well-founded nature of Michelet's technique of osteosynthesis.


Isotope gastric emptying tests in clinical practice: expectation, outcome, and utility.
Tests of gastric emptying with modern scintigraphic methods are recommended in the clinical management of gastric disorders. An audit of 472 gastric emptying tests carried out over a 10 year period was performed to discover the reasons for requests from consultant clinicians, their anticipation of the results of tests, and the influence of the results upon the subsequent management of their patients. Excluding control (n = 47) and research (n = 50) studies, there were 375 clinical referrals that could be grouped under the headings: non-ulcer dyspepsia (n = 72), suspected diabetic gastroparesis (n = 18), peptic ulcer (n = 15), suspected delayed gastric emptying after surgery (n = 154), dumping and diarrhoea (= 107), and other indications (n = 9). Although the results were abnormal for 55 (48%) of the 'medical' patients, they did not seem to influence clinical management. Delayed gastric emptying after surgery was confirmed in only 20% of patients referred with this clinical diagnosis. Conversely, most (79%) o the patients referred with dumping and diarrhoea exhibited abnormally rapid emptying. Isotope gastric emptying studies may be useful in clinical practice. The results are often at variance with the clinical diagnosis. Clinicians must take into account the nature of the test meal used when results are correlated with clinical features.


[Outcomes of combined pulmonary resection and off-pump coronary artery bypass grafting for patients with lung tumor and concurrent coronary heart disease].
To analyze the outcomes of lung resection and off-pump coronary artery bypass grafting (OPCAB) synchronously for the patients with lung tumor and concurrent coronary heart disease. Twenty-two patients with lung tumor and concurrent coronary heart disease underwent combined surgical interventions between January 2003 and December 2011. They included 20 males and 2 females with a mean age of (65 ± 4) years. The TNM stage of lung cancer was predominantly at stages I and II. A majority of them had two and three-vessel disease. The tests of cardiothoracic functions were normal. The biopsy of lung tumor was carried out initially through sternotomy approach. Then OPCAB was performed. Finally lung resection was carried out according to the pathological results of lung tumor. All patients survived. The average number of anastomosed coronary vessels was 2.3. After myocardial revascularization through a sternotomy approach, the procedures included lobectomy and partial lung resections through sternotomy only (n = 11), lobectomy through a lateral thoracotomy approach (n = 9) and lobectomy and bypass to left anterior descending (LAD) through left thoracotomy only (n = 2). Neither death nor new MI occurred during the perioperative period. The mean stay in-hospital was (17 ± 7) days and mean operative duration (233 ± 1) min. The diagnoses were non-small cell lung cancer (n = 18) and benign tumor (n = 4). The most frequent complications were cardiac arrhythmias, atelectasis and pulmonary infections. All of them were followed up for 10-60 months. Within this period, 4 patients died from cancer recurrence. The combined procedure of OPCABG grafting and pulmonary resection is a safe and effective treatment option for patients with lung cancer and concurrent coronary heart disease.


[Not Available].
Pathological changes of bones are described and diagnosed by microscopic and radiological methods. The bones of the chosen four cases were discovered in the town - church of Winterthur in 1980 and in the Nanikon - Buhl, Kanton Zurich, Switzerland between 1992 and 1994. The aim was to get a diagnosis and differential diagnosis by analyzing the microscopic and radiological findings. The fractures of cases three and four were analyzed with older literature, different than that of the first case where the shoulder examination was analyzed with recent literature. In the first case it was also possible to detect disease of the soft tissue due to the pathological findings on the bones examined.


Programmatic and ethical challenges in the implementation of treatment-as-prevention in the context of HIV and drug-resistant tuberculosis co-infection in sub-Saharan Africa.
There is limited literature on programmatic challenges in the implementation of a treatment-as-prevention (TasP) strategy among human immunodeficiency virus (HIV) and drug-resistant tuberculosis (DR-TB) co-infected individuals in sub-Saharan Africa (SSA). This paper highlights specific programmatic challenges surrounding the implementation of this strategy among HIV and DR-TB co-infected populations in SSA. In SSA, limitations in administrative, human and financial resources and poor health infrastructure, as well as increased duration and complexity of providing long-term treatment for HIV individuals co-infected with DR-TB, pose substantial challenges to the implementation of a TasP strategy and warrant further investigation. A comprehensive approach must be devised to implement TasP strategy, with special attention paid to the sizable HIV and DR-TB co-infected populations. We suggest that evidence-informed and human rights-based guidelines for participant protection and strategies for programme delivery must be developed and tailored to maximise the benefits to those most at risk of developing HIV and DR-TB co-infection. Assessing regional circumstances is crucial, and TasP programmes in the region should be complemented by combined prevention strategies to achieve the intended goals.


Atrial fibrillation in immigrant groups: a cohort study of all adults 45 years of age and older in Sweden.
To study the association between country of birth and incident atrial fibrillation (AF) in several immigrant groups in Sweden. The study population included all adults (n = 3,226,752) aged 45 years and older in Sweden. AF was defined as having at least one registered diagnosis of AF in the National Patient Register. The incidence of AF in different immigrant groups, using Swedish-born as referents, was assessed by Cox regression, expressed in hazard ratios (HRs) and 95% confidence intervals (CI). All models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, and neighbourhood socioeconomic status. Compared to their Swedish-born counterparts, higher incidence of AF [HR (95% CI)] was observed among men from Bosnia 1.74 (1.56-1.94) and Latvia 1.29 (1.09-1.54), and among women from Iraq 1.96 (1.67-2.31), Bosnia 1.88 (1.61-1.94), Finland 1.14 (1.11-1.17), Estonia 1.14 (1.05-1.24) and Germany 1.08 (1.03-1.14). Lower incidence of AF was noted among men (HRs ≤ 0.60) from Iceland, Southern Europe (especially Greece, Italy and Spain), Latin America (especially Chile), Africa, Asia (including Iraq, Turkey, Lebanon and Iran), and among women from Nordic countries (except Finland), Southern Europe, Western Europe (except Germany), Africa, North America, Latin America, Iran, Lebanon and other Asian countries (except Turkey and Iraq). In conclusion, we observed substantial differences in incidence of AF between immigrant groups and the Swedish-born population. A greater awareness of the increased risk of AF development in some immigrant groups may enable for a timely diagnosis, treatment and prevention of its debilitating complications, such as stroke.


Differential Use of Screening Mammography in Older Women Initiating Metformin versus Sulfonylurea.
Differential use of screening mammography may lead to biased detection of breast cancer. This study aimed to compare receipt of screening mammography and the incidence of screen-detected breast cancer between metformin and sulfonylurea initiators. We used 2006-2014 US Medicare claims to identify initiators of metformin or sulfonylurea aged 65+ years continuously enrolled in Parts A/B for ≥2 years pre-initiation and ≥2 years post-initiation. We reported frequencies of screening mammograms and screen-detected breast cancer in 1 year pre-initiation among all cohort members and in 1 year post-initiation among cancer-free cohort members. Weighted screening risk differences (RDs) were estimated comparing metformin to sulfonylurea group. We identified 41,436 and 13,367 initiators of metformin and sulfonylurea, 35% and 24% of which had ≥1 screening mammogram in 1 year pre-initiation (weighted RD: 6 percentage points; 95% CI: 5 to 7), respectively. The weighted RD for screen-detected breast cancer associated with metformin was 0.00 percentage points (95% CI: -0.09 to 0.09). Among cancer-free cohort members, metformin initiators had 5 percentage points (95% CI: 4 to 6) and 0.11 percentage points (95% CI: -0.02 to 0.23) absolute risk excess of screening mammography and screen-detected breast cancer in 1 year post-initiation, compared with sulfonylurea initiators, respectively. Metformin initiators were more likely to receive screening mammograms than sulfonylurea initiators pre- and post-initiation, indicating possible detection bias due to differential screening mammography. Researchers should be aware of the potential for more screening mammograms pre- and post-initiation when interpreting the findings of metformin on breast cancer incidence. Copyright © 2017 John Wiley & Sons, Ltd.


Lactate's behavioral switch in the brain: An in-silico model.
Emerging evidence emphasizes lactate's involvement in both physiological processes (energy metabolism, memory, etc.) and disease (traumatic brain injury, epilepsy, etc.). Furthermore, the usefulness of mathematical modeling in deciphering underlying dynamics of the brain to investigate lactate roles and mechanisms of action has been well established. Here, we analyze a novel mathematical model of brain lactate exchanges between four compartments: neurons, astrocytes, capillaries, and extracellular space. A system of four ordinary differential equations is proposed to explain interactions between these compartments. We first optimize and analyze the model's parameters under normal, resting state conditions, and then use it to simulate changes linked to elevated arterial lactate. Our results show that even though increased arterial lactate results in increased uptake by astrocytes and release to the extracellular space, it cannot strongly recover the initial drop in neuronal lactate concentration. Also, we show that the direction of lactate transport between the compartments is influenced by the maximum astrocyte production rate and the transport rate between astrocytes and extracellular space.


Geophagy during pregnancy: Is there a health risk for infants?
Prenatal lead exposure is a public health concern. Geophagy, the practice of soil eating, is documented for pregnant women of sub-Saharan Africa to treat pregnancy-related malaise. The soils however can contain substantial amounts of lead. In an exploratory study on 48 mother-child pairs in the Democratic Republic of Congo, we found striking site-specific differences in prenatal lead exposure, i.e., higher lead levels at Kisangani than at Isiro. Kisangani women consumed 1/ more often soil during the first trimester of pregnancy as well as 2/ a different type of soil compared to Isiro women (P<0.05). We conclude geophagy may be a potential source of prenatal lead exposure.


The role of National Immunization Technical Advisory Groups in advising COVID-19 immunization policy during the pandemic: lessons from the Federation of Bosnia and Herzegovina.
A National Immunization Technical Advisory Group (NITAG) is a multi-disciplinary body of experts that provides evidence-based recommendations on immunizations to policy-makers to assist them in making immunization policy and program decisions. NITAGs faced challenges in making evidence-based recommendations for COVID-19 vaccines during the COVID-19 pandemic due to the new vaccine products available in a short time period and limited available data on vaccine effectiveness and vaccine safety. The authors reviewed the process used by the NITAG in the Federation of Bosnia and Herzegovina, called the expert body, to develop COVID-19 vaccine recommendations. The article reviews the evidence that was considered by the expert body when developing 23 recommendations on COVID-19 vaccination and describes the challenges and successes faced by the body. The expert body recommendations led to the successful roll-out of COVID-19 vaccines and provided guidance for COVID-19 vaccination during the pandemic. The expert body plans to improve its work and procedures for developing routine immunization recommendations with the support of the WHO Regional Office for Europe.


Interferon induction by and toxicity of polyriboinosinic acid [poly(rI)].polyribocytidylic acid [poly (rC)], mismatched analog poly (rI).poly[r(C12Uracil)n], and poly(rI).poly(rC) L-lysine complexed with carboxymethylcellulose.
The ability of polyriboinosionic acid [poly(rI)].polyribocytidylic acid [poly(rC)], mismatched analog poly (rI).poly[r(C12Uracil)n], and poly(rI).poly(rC) complexed with poly L-lysine and carboxymethylcellulose [poly(ICLc)] to induce interferon and the comparative toxicity of each in cats were evaluated. Each induced high levels of circulating interferon, although poly(ICLC) injected intravenously at 1 to 4 mg/kg induced up to 10 times more interferon than the other compounds. Each compound was pyrogenic and caused a transient decrease in leukocyte numbers. Poly(rI).poly(rC) and the mismatched analog caused severe diarrhea and nausea at the highest drug concentrations (1 to 4 mg/kg), but poly (ICLC) did not. Each compound also caused depression and lethargy and impaired coordination.


[Standardized diagnosis and treatment of colorectal liver metastasis].
Colorectal cancer is one of the most common malignancies. The liver is the most common site of distant metastasis, and liver metastasis is the leading cause of death in the patients with colorectal cancer. In recent years, the concept of diagnosis and treatment in colorectal liver metastasis (CLM) and the liver surgery techniques developed rapidly, the standardization of clinical practice elevated obviously, and the survival outcomes of more and more patients were significantly improved. Standardization of diagnosis and treatment in CLM comprised overall assessment of patients' condition and local tumor status based on multidisciplinary team collaboration and then institution of treatment strategy. Standardization of CLM diagnosis should be carried out by abdominal enhancement CT, or liver ultrasound to evaluate the hepatic metastasis. As for suspected CLM, serum AFP and liver MRI are recommended. When resectability is assessed, both surgery techniques (procedures, liver preservation, and resectable lesions outside of liver) and oncology items (synchronism, heterochronism, invasion and progression) must be considered. Due to complicated illness and different prognosis, CLM patients should be carefully classified to receive associated treatment. For CLM patients with resectable or potentially resectable lesions, the aim of treatment is to increase the R0 resection rate and survival. For those with unresectable lesions, the aim is to improve tumor-associated symptoms and maintain the quality of life.


Prolonged inhibitory effects against planktonic growth, adherence, and biofilm formation of pathogens causing ventilator-associated pneumonia using a novel polyamide/silver nanoparticle composite-coated endotracheal tube.
Microbial cells can rapidly form biofilm on endotracheal tubes (ETT) causing ventilator-associated pneumonia, a serious complication in patients receiving mechanical ventilation. A novel polyamide with a good balance of hydrophilic/hydrophobic moieties was used for the embedment of green-reduction silver nanoparticles (AgNPs) for the composite-coated ETT. The films were conformal with a thickness of ∼ 17 ± 3 µm accommodating high loading of 60 ± 35 nm spherical-shaped AgNPs. The coated ETT resulted in a significant difference in reducing both planktonic growth and microbial adhesion of single and mixed-species cultures, compared with uncoated ETT (p < 0.05). A time-kill assay demonstrated rapid bactericidal effects of the coating on bacterial growth and cell adhesion to ETT surface. Biofilm formation by Pseudomonas aeruginosa and Staphylococcus aureus, commonly encountered pathogens, was inhibited by > 96% after incubation for 72 h. Polyamide/AgNP composite-coated ETT provided a broad-spectrum activity against both Gram-positive and Gram-negative bacteria as well as Candida albicans and prolonged antimicrobial activity.


The clinical use of karyotyping spontaneous abortions.
The objective of this study was to assess the clinical use of routinely karyotyping spontaneous abortion material. We retrospectively reviewed the records of the Pittsburgh Cytogenetics Laboratory from January 1, 1998, to December 31, 2001, for all tissues from spontaneous losses at 20 weeks' gestation or less for which complete medical records were available. There were 517 submitted samples of which 28 (5.4%) failed to grow in culture. Overall, 55.8% of samples were abnormal; 52.3% of normal results were male. In samples from pregnancies at 13 weeks or less the rate of abnormality was 69.1%. When analyzed by maternal age, the rate of abnormality for first-trimester losses was 57.2% in women younger than 35 years, and 82.3% in those 35 years or older. There was no difference in the rate of abnormality when comparing first loss with two or more losses, first pregnancy with two or more pregnancies, or the presence or absence of at least one live birth. Chromosome abnormalities are the cause for pregnancy loss in 50% to 80% of cases, depending on maternal age and gestational age at time of the loss. Karyotyping of spontaneous losses in the first trimester beginning with the patient's second loss provides clinically important etiologic information and decreases the number of evaluations necessary for recurrent pregnancy loss.


Epiphysiodesis Screw Bending.
Percutaneous epiphysiodesis using transphyseal screws is a common method for treatment of limb length discrepancy and angular deformity. The authors report 3 cases of a previously unreported complication following treatment with percutaneous epiphysiodesis using transphyseal screws: bending of the transphyseal screw. In each case, this rare complication was associated with difficult removal of the screw. This retrospective case report accessed the medical records of 3 children, 2 boys and 1 girl, 9 to 14 years old. All of the children had 4.0-mm cannulated stainless steel screws ranging from 40 to 50 mm in length. Two of the patients had partially threaded and 1 had fully threaded screws with bending noted a minimum of 6 months following implantation. Additionally, each of the screws bent near the physis of the bone, which was not located at the center of the screw in every case or at the transition from threaded to nonthreaded portions in each partially threaded screw. To the authors' knowledge, these are the first reported cases of cannulated screw bending following transphyseal tibial or femoral placement for the correction of leg length or angular deformity in a pediatric population. Although the true incidence rate is unknown, screw bending following percutaneous epiphysiodesis presents complications in the hardware removal process. Further biomechanical tests should be conducted to determine the best screw design to minimize bending of transphyseal screws from physiologic growth. [Orthopedics. 2017; 40(4):e717-e720.].


Laboratory and field tests of the effectiveness of the lemon-eucalyptus extract, Citridiol, as a repellent against land leeches of the genus Haemadipsa (Haemadipsidae).
Citridiol is an extract of the leaves of Corymbia citriodora (Myrtaceae), the lemon eucalyptus, and mostly consists of p-menthane-3,8-diol isomers. The effectiveness of this extract as a repellent against land leeches of the genus Haemadipsa (Haemadipsidae), primarily H. sylvestris, was tested in the laboratory and field, in Peninsular Malaysia. The formulation tested, Mosi-guard Natural spray, contained 40% (w/w) Citridiol in a base of ethanol, water and isopropanol. In the laboratory test, specimens of H. sylvestris that were placed within moist, untreated arenas enclosed by treated paper rings made numerous attempts to cross the rings but were prevented or delayed from crossing over, in a dose-dependent manner. Mortality was high among the leeches that attempted to cross over the paper rings that had been sprayed to saturation point but low among the leeches that attempted to cross over paper rings that had only been partially treated, with a droplet-spray. The field study was carried out using indices that were formulated to reflect the severity of leech attack and the degree of repellency. Heavy or moderate spraying of footwear and trouser legs (tucked into socks) not only gave complete protection against bites by H. sylvestris and H. picta but also provided high enough repellency to keep the treated footwear virtually free of leeches. Even a light spray greatly reduced the numbers of leeches on footwear and delayed their progression toward biting the test subjects, although it failed to prevent bites completely. There was no decline in the repellency of the Citridiol when hourly assessments were made over a 6-h test period in the field. The results of the study show that Citridiol is highly repellent as well as toxic to leeches, and can be effectively used to prevent leech bites in the field.


The role of nutraceuticals in the prevention of cardiovascular disease.
Cardiovascular disease (CVD) ranks among the most common health-related and economic issues worldwide. Dietary factors are important contributors to cardiovascular risk, either directly, or through their effects on other cardiovascular risk factors including hypertension, dyslipidemia and diabetes mellitus. Nutraceuticals are natural nutritional compounds, which have been shown to be efficacious in preventative medicine or in the treatment of disease. Several foods and dietary supplements have been shown to protect against the development of CVD. The aim of this review is to present an update on the most recent evidence relating to the use of nutraceuticals in the context of the prevention and treatment of CVD.


Models of health care.
Using nursing models is part of the systematic decision-making that underpins nursing practice. Using a health-care model is a central feature of being a responsible practitioner. Part 3 of this module considers a number of models of health care.


[Nutritional status of patients with different types of gastroesophageal reflux disease].
The aim of the study was to assess dietary intake in patients with erosive (ERD) and non-erosive reflux disease (NERD). One hundred and sixty seven patients (103 women and 64 men, mean age 47±13,6 years) were divided according to symptoms and endoscopic findings into three groups: 88 patients with NERD, 38 patients with ERD and 41 healthy controls. Symptoms were scored by validated GERDQ questionnaire, dietary intake was assessed by validated food questionnaire and 24-h pH/impedance monitoring was used for confirmation of pathological reflux. All groups were homogenous by age and sex, both NERD and ERD patients demonstrated higher BMI (28.1±6.5 vs 28.4±6.1 kg/m2) in compare to the patients from control group (24.3±2.8 kg/m2). Average daily calorie intake was higher in patients with NERD and ERD (2579±854 vs 2467±710 kcal/day) in compare to the control group (2093±696 kcal/day) due to increased consumption of fat (121±52 vs 112±52 g/day) and carbohydrates (244±88 vs 216±64 g/day) consequently. Consumption of dietary fiber was low in all groups in compare to recommended daily allowance, but even lower in NERD and ERD patients in compare to control (6.0±3.8 g/day vs 5.2±4.8 g/day vs 9.45±5.6 g/day). There was direct correlation between gastroesophageal reflux disease (GERD) and average energy consumption (R=0.23, p<0.05) and daily total fat consumption (R=0.21, p<0.05), but inverse correlation with consumption of dietary fiber (R=-0.23, p<0.05). Consumption of alcohol was higher in NERD patients in compare with ERD patients and control group (1.2±4.9 vs 0.2±2.6 vs 0±0.87 g/day), but generally it was low. Total daily number of refluxes as well as number of acid refluxes were highly correlated with daily consumption of energy (R=0.35, p<0.05; R=0.35, p<0.05), fat (R=0.33, p<0.05; R=0.32, p<0.05) and protein (R=0.3, p<0.05; R=0.25, p<0.05), however inverse correlation was found between total number of refluxes and consumption of fibers (R=-0.22, p<0.05). There was no correlation between consumption of carbohydrates or alcohol and total number of refluxes or acid refluxes. In conclusion, GERD is associated with higher BMI, increased consumption of calories and fat and low consumption of dietary fiber. Total number of refluxes is related to consumption of fat and fibers. No association with consumption of carbohydrates or alcohol was found. These findings need to be taken in account for prescription of diet to GERD patients.


[The forecasting of the time of calving using a rapid progesterone test].
The rectal temperature and any alterations in eight different external signs of parturition were investigated twice daily in 22 "Deutsche Schwarzbunte" cows during the last 10 days of gestation. There was great variation in the externally detectable signs of parturition during the preparatory stages and short before labour. During the same time period, plasma progesterone and total oestrogens were determined using radioimmunology. From 60 hours to 12 hours prior to calving the progesterone levels fell rapidly to 0.77 +/- 0.22 ng/ml. Additionally, the plasma progesterone was determined semi-quantitatively in 31 cows using a rapid progesterone assay in order to predict the commencement of parturition within 36 hours. This allowed a more objective and reliable assessment of calving time than the evaluation of external signs of labour.


Psychogenic origins of multiple chemical sensitivities syndrome: a critical review of the research literature.
The purpose of this review was to critically evaluate research on the psychogenic origins of multiple chemical sensitivities (MCS) syndrome. Using as keywords environmental illness, multiple chemical sensitivities, and clinical ecology, two databases--PsychLit and Medline--were searched by computer; reference lists of all articles located were also searched manually. Ten articles meeting three criteria were selected for review. Five sample selection problems, seven measurement problems, and three study design problems were common in all but one of the articles reviewed. Current studies investigating psychogenic hypotheses of MCS syndrome are methodologically problematic and their conclusions questionable. Studies of psychiatric profiles observed in MCS syndrome need to be designed to differentiate between competing psychogenic and biogenic hypotheses.


Identification of Circulating Long Noncoding RNA Linc00152 as a Novel Biomarker for Diagnosis and Monitoring of Non-Small-Cell Lung Cancer.
Long noncoding RNAs (lncRNAs) have been reported to play vital roles in non-small-cell lung cancer (NSCLC). Recently, long noncoding RNA Linc00152 has been reported to play important roles in various cancers. In this study, our aim was to investigate its expression pattern and clinical significance and further evaluate its diagnostic value for NSCLC. The levels of Linc00152 were detected in NSCLC tissues and plasma samples by quantitative real-time PCR (qRT-PCR). Receiver operating characteristic (ROC) curves were depicted to evaluate the diagnostic value. We found that Linc00152 levels were upregulated in both NSCLC tissues and plasma samples. Plasma Linc00152 levels were significantly lower in postoperative samples than in preoperative samples. Besides, high Linc00152 expression was significantly correlated with tumor size (r = 0.293, P = 0.005) and tumor stage (r = 0.324, P = 0.011). The ROC curves indicated that plasma Linc00152 has high diagnostic accuracy for NSCLC, and the area under curve (AUC) for NSCLC versus healthy was 0.816 (95% CI: 0.757-0.875). Moreover, we found that the combination of Linc00152 and CEA could provide a more powerful diagnosis efficiency than Linc00152 or CEA alone (AUC = 0.881, 95% CI: 0.836-0.926). Plasma Linc00152 could serve as a promising biomarker for diagnosing and monitoring NSCLC.


Assessment of a daily online implanted fiducial marker-guided prostate radiotherapy process.
The aims of this study were to investigate whether intrafraction prostate motion can affect the accuracy of online prostate positioning using implanted fiducial markers and to determine the effect of prostate rotations on the accuracy of the software-predicted set-up correction shifts. Eleven patients were treated with implanted prostate fiducial markers and online set-up corrections. Orthogonal electronic portal images were acquired to determine couch shifts before treatment. Verification images were also acquired during treatment to assess whether intrafraction motion had occurred. A limitation of the online image registration software is that it does not allow for in-plane prostate rotations (evident on lateral portal images) when aligning marker positions. The accuracy of couch shifts was assessed by repeating the registration measurements with separate software that incorporates full in-plane prostate rotations. Additional treatment time required for online positioning was also measured. For the patient group, the overall postalignment systematic prostate errors were less than 1.5 mm (1 standard deviation) in all directions (range 0.2-3.9 mm). The random prostate errors ranged from 0.8 to 3.3 mm (1 standard deviation). One patient exhibited intrafraction prostate motion, resulting in a postalignment prostate set-up error of more than 10 mm for one fraction. In 14 of 35 fractions, the postalignment prostate set-up error was greater than 5 mm in the anterior-posterior direction for this patient. Maximum prostate rotations measured from the lateral images varied from 2 degrees to 20 degrees for the patients. The differences between set-up shifts determined by the online software without in-plane rotations to align markers, and with rotations applied, was less than 1 mm (root mean square), with a maximum difference of 4.1 mm. Intrafraction prostate motion was found to reduce the effectiveness of the online set-up for one of the patients. A larger study is required to determine the magnitude of this problem for the patient population. The inability in the current software to incorporate in-plane prostate rotations is a limitation that should not introduce large errors, provided that the treatment isocentre is positioned near the centre of the prostate.


Vascular inflammatory, oxidative and protease-based processes: implications for neuronal cell death in Alzheimer's disease.
A substantial literature demonstrates activation of inflammatory processes in the Alzheimer's disease (AD) brain and an association between inflammation and oxidative stress. We have shown that brain microvessels from AD patients express high levels of inflammatory proteins and that these proteins evoke release of the neurotoxic protease thrombin from brain endothelial cells. The objective of this study was to determine the effects of inflammatory proteins on brain endothelial cell reactive oxygen species generation, protease release and cell apoptosis. Also, the effects of inflammatory proteins on neuronal reactive oxygen species generation, injury and apoptosis were assessed. Treatment of cultured brain endothelial cells with inflammatory proteins (LPS, IL-1beta, IL-6, IFN-gamma, TNF-alpha) resulted in a significant increase (p < 0.01) in intracellular levels of reactive oxygen species by 1 h. Inflammatory proteins also caused release of tissue plasminogen activator and increased apoptosis by 24 h in these cells. In cultured neurons, inflammatory proteins caused an increase in reactive oxygen species, membrane fluidity, and apoptosis by 24 h, as detected by fluorescent microscopy. Taken together, these data support the hypothesis that vascular inflammatory, oxidative and protease-based processes contribute to neuronal cell death, and suggest that therapies targeted at these mediators and processes could be effective in AD.


Intra-articular injection of synthetic microRNA-210 accelerates avascular meniscal healing in rat medial meniscal injured model.
The important functions of the meniscus are shock absorption, passive stabilization and load transmission of the knee. Because of the avascularity of two-thirds of the meniscal center region, the treatment of tears in this area is hard. Recently, microRNAs have been proven to play an important role in the pathogenesis of diseases. We focused on microRNA (miR)-210, which plays a wide spectrum of roles comprising mitochondrial metabolism, angiogenesis, DNA repair and cell survival. This study aimed to investigate the effect of intra-articular injection of synthetic miR-210 on the injured meniscus in the avascular zone. The middle segments of the medial meniscus of Spraque Dawley rats were incised longitudinally with a scalpel. An intra-articular injection of double-stranded (ds) miR-210 (for control group using control dsRNA) with atelocollagen was administered immediately after injury. Four weeks and 12 weeks after the injection, we conducted a histologic evaluation, immunohistochemical evaluation and Real-time PCR analysis. In vitro, the inner meniscus and synovial cells were isolated from rat knee joint, and were transfected with ds miR-210 or control dsRNA. Real-time PCR and immunohistochemical evaluations were performed. Twenty-four hours after the injection, FAM (Fluorescein amidite) labeled miR-210 was observed in the cells around the injured site. Four weeks after the injection, the injured site of the miR-210 group was filled with repaired tissue while that of the control was not repaired. In gene expression analysis of the meniscus, the expression of miR-210, Collagen type 2 alpha 1 (Col2a1), Vascular endothelial growth factor (VEGF), and Fibroblast growth factor-2 (FGF2) in the miR-210 group was significantly higher than that in the control. At 12 weeks, the intra-articular injection of miR-210 had healed the injured site of the meniscus and had prevented articular cartilage degeneration. In vitro, miR-210 upregulated Col2a1 expression in the meniscus cells and VEGF and FGF2 expression in the synovial cells. An intra-articular injection of ds miR-210 was effective in the healing of the damaged white zone meniscus through promotion of the collagen type 2 production from meniscus cells and through upregulated of VEGF and FGF2 from synovial cells.