The Effect of Adding Virtual Reality Training on Traditional Exercise Program on Balance and Gait in Unilateral, Traumatic Lower Limb Amputee.
Objective: Lower limb amputation is common in war combat and armed conflict as well as in traumatic settings and presents a challenge for health care providers. The incorporation of advanced technologies, particularly virtual reality, presents an opportunity to address the main consequences of amputation, principally balance and gait. The aim of this study was to investigate the additional effect of virtual reality with a traditional rehabilitation exercise program on balance and gait in unilateral, traumatic lower limb amputees. Materials and Methods: Thirty-two traumatic lower limb amputees, fulfilling a postfitting rehabilitation program at least 6 months ago, were recruited and randomly assigned into two identically sized groups; group C (control group) experiencing the traditional exercise program and group VR (virtual reality group) experiencing an addition of a virtual reality training. The intervention was conducted over 6 weeks at a rate of three sessions per week. Outcome measures assessed before and after 6 weeks were the Berg Balance Scale (BBS), Timed Up and Go (TUG) test, Dynamic Gait Index (DGI), and 6-minute walk test (6 MWT). Results: Both interventions induced improvement in all measured parameters (P < 0.05); however, virtual reality demonstrated significant superior effects only on the balance markers, TUG test, DGI, and BBS (P < 0.05), but not on the 6 MWT (P > 0.05). Conclusion: Virtual reality is a promising, amusing, and safe intervention for addressing balance and gait in unilateral, traumatic lower limb amputees.


Argyrophilic grain disease is a sporadic 4-repeat tauopathy.
Argyrophilic grain disease (AGD) was first reported as an adult-onset dementia, but recent studies have emphasized personality change, emotional imbalance, and memory problems as clinical features of AGD. AGD is characterized by spindle- or comma-shaped argyrophilic grains in the neuropil of entorhinal cortex, hippocampus, and amygdala. Immunohistochemistry with monoclonal antibodies specific to tau isoforms with four (4R) or three (3R) repeats in the microtubule-binding domain showed immunostaining of grains with 4R, but not 3R, tau antibodies, suggesting that AGD was a 4R tauopathy. The tau isoform composition of AGD was confirmed with densitometric analysis of Western blots of sarkosyl-insoluble tau from the medial temporal lobe of AGD brains with a range of concurrent neurofibrillary pathology and compared with Alzheimer controls. The 4R/3R ratio was 1 or less for Alzheimer disease; the 4R/3R ratio was more than 1 for AGD, decreasing with increasing neurofibrillary pathology and demonstrating that insoluble tau in AGD was enriched in 4R tau. The frequency of the extended tau haplotype was not different in AGD compared to other sporadic 4R tauopathies, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Furthermore, AGD occurred in PSP and CBD more frequently than in dementia controls, including Alzheimer disease. These results suggest that AGD, PSP and CBD are 4R tauopathies that share common pathologic, biochemical, and genetic characteristics.


Stochastic resonance improves vision in the severely impaired.
We verified whether a stochastic resonance paradigm (SR), with random interference ("noise") added in optimal amounts, improves the detection of sub-threshold visual information by subjects with retinal disorder and impaired vision as it does in the normally sighted. Six levels of dynamic, zero-mean Gaussian noise were added to each pixel of images (13 contrast levels) in which alphabet characters were displayed against a uniform gray background. Images were presented with contrast below the subjective threshold to 14 visually impaired subjects (age: 22-53 yrs.). The fraction of recognized letters varied between 0 and 0.3 at baseline and increased in all subjects when noise was added in optimal amounts; peak recognition ranged between 0.2 and 0.8 at noise sigmas between 6 and 30 grey scale values (GSV) and decreased in all subjects at noise levels with sigma above 30 GSV. The results replicate in the visually impaired the facilitation of visual information processing with images presented in SR paradigms that has been documented in sighted subjects. The effect was obtained with low-level image manipulation and application appears readily possible: it would enhance the efficiency of today vision-improving aids and help in the development of the visual prostheses hopefully available in the future.


Local skin reaction in mice and guinea pigs induced by a single intradermal inoculation of Fusobacterium necrophorum lipopolysaccharide.
Dermal responses induced by Fusobacterium necrophorum strain VPI 2891 lipopolysaccharide (LPS) were studied using mice and guinea pigs. In ddY mice, the LPS elicited inflammatory, haemorrhagic lesions and an increase in local vascular permeability 24 h postinjection. Of the mouse strains, C3H/HeJ mice were less sensitive. The LPS induced erythema and haemorrhagic responses in guinea pig skin 24 h postinoculation. These responses were dose-dependent. The intensity of dermal inflammation-inducing activity of F. necrophorum LPS was similar to that of Escherichia coli strain 055:B5 LPS, but weaker than that of Salmonella typhimurium LPS. These findings suggest that the fusobacterial LPS may play an important role in contributing to produce the initial lesions in the bacterial infection.


Nitrate contamination in groundwater on an urbanized dairy farm.
Urbanization of rural farmland is a pervasive trend around the globe, and maintaining and protecting adequate water supplies in suburban areas is a growing problem. Identification of the sources of groundwater contamination in urbanized areas is problematic, but will become important in areas of rapid population growth and development. The isotopic composition of NO3 (delta15N(NO3) and delta18O NO3), NH4 (delta15N(NH4)), groundwater (delta2H(wt) and delta18O(wt)) and chloride/bromide ratios were used to determine the source of nitrate contamination in drinking water wells in a housing development that was built on the site of a dairy farm in the North Carolina Piedmont, U.S. The delta15N(NO3) and delta18O NO3 compositions imply that elevated nitrate levels at this site in drinking well water are the result of waste contamination, and that denitrification has not significantly attenuated the groundwater nitrate concentrations. delta15N(NO3) and delta18O(NO3) compositions in groundwater could not differentiate between septic effluent and animal waste contamination. Chloride/ bromide ratios in the most contaminated drinking water wells were similar to ratios found in animal waste application fields, and were higher than Cl/Br ratios observed in septic drain fields in the area. delta18O(wt) was depleted near the site of a buried waste lagoon without an accompanying shift in delta2H(wt) suggesting water oxygen exchange with CO2. This water-CO2 exchange resulted from the reduction of buried lagoon organic matter, and oxidation of the released gases in aerobic soils. delta18O(wt) is not depleted in the contaminated drinking water wells, indicating that the buried dairy lagoon is not a source of waste contamination. The isotope and Cl/Br ratios indicate that nitrate contamination in these drinking wells are not from septic systems, but are the result of animal waste leached from pastures into groundwater during 35 years of dairy operations which did not violate any existing regulations. Statutes need to be enacted to protect the health of the homeowners that require well water to be tested prior to the sale of homes built on urbanized farmland.


Plasma fibronectin in idiopathic myelofibrosis and related chronic myeloproliferative disorders.
Plasma fibronectin concentrations were measured in 49 patients with chronic myeloproliferative disorders and compared to sex- and age-matched controls. A significantly lower plasma fibronectin concentration was observed in patients with idiopathic myelofibrosis as compared with the control group (p less than 0.01). In addition, plasma fibronectin concentrations in myelofibrosis patients differed significantly, when compared with patients with polycythaemia vera (p less than 0.01), whereas no significant difference was found between myelofibrosis patients and those with a transitional myeloproliferative disorder or chronic myelogenous leukaemia (p greater than 0.05). An inverse relationship was demonstrated between plasma fibronectin and spleen size, the lowest plasma fibronectin levels being found in patients with large spleens. It is supposed that low plasma fibronectin concentrations in splenomegalic patients may be due to enhanced consumption of the opsonin in the expanded splenic mononuclear-macrophage system.


The relationship of oral malodor in patients with or without periodontal disease.
Halitosis has been correlated with the concentration of volatile sulfur compounds (VSC) produced in the oral cavity by metabolic activity of bacteria colonizing the periodontal area and the dorsum of the tongue. The aim of this study was to determine whether there is some relationship between the presence of N-benzoyl-DL-arginine-2-napthylamide (BANA)-positive species Treponema denticola, Porphyromonas gingivalis, and Bacteroides forsythus and clinical and oral malodor parameters. Twenty-one subjects (21 to 59 years old) with probing depths (PD) > 3.0 mm and 20 subjects (21 to 63 years old) with PD < or = 3.0 mm (controls) participated. The quality of the mouth air was assessed organoleptically, and a portable sulfide monitor was used to measure the concentration of VSC. Clinical parameters, plaque index (PI) and gingival index (GI), were obtained from 6 teeth. Samples for BANA test were taken from the dorsal surface of the tongue, saliva, and the 6 reference teeth. The scores of PI, GI, subgingival samples that tested positive for BANA hydrolyzing species, organoleptic ratings, and VSC values were significantly higher in the subjects with PD > 3.0 mm (P < 0.01, Mann-Whitney U test). There was a correlation between BANA hydrolysis by subgingival plaque bacteria and VSC values (r = 0.55, P < 0.01), and between GI and VSC values (r = 0.48, P < 0.05) in patients with PD > 3.0 mm. There was no significant correlation between these parameters in the control group. These results confirm that the BANA hydrolyzing bacteria in the subgingival plaque are an important source of malodor production in the oral cavity.


Update on risk factors and biomarkers of sudden unexplained cardiac death.
Sudden cardiac death (SCD) accounts for approximately 15%-20% of all deaths worldwide, the causes of which are mainly structural heart diseases. However, SCD also occurs in patients without major cardiac structural abnormalities due to electrophysiological abnormalities or other unexplained causes which account for about 1%-15% cases of SCD, namely sudden unexplained cardiac death (SUCD). The causes of SUCD cannot be explained by routine forensic pathological examination. Hence, identifying the causes of SUCD remains a major challenge in forensic fields. Consequently, it is significant to discover the risk factors and molecular biomarkers for diagnosis and prediction of SUCD. SUCD can be at least partially explained by acute and chronic psychological stress, such as Takotsubo cardiomyopathy (TCM), which is increasingly recognized as a potentially modifiable risk factor for SUCD. Additionally, the inherited lethal cardiac arrhythmia due to ion channelopathies is one of the causes of SUCD. However, SCD resulted from psychological stress or lethal cardiac arrhythmia lacks postmortem observable morphological evidence. Therefore, the postmortem diagnosis of SUCD remains a primary challenge in forensic pathology because of the absence of recognized diagnostic biomarkers. Recent advances in knowledge give us additional possibility in understanding the cause of SUCD. In this review, we summarized the updated risk factors of SUCD including genetics and psychological stress, as well as the potential diagnostic biomarkers of SUCD, such as micro-RNAs, heat shock proteins, Galectin-3 and inflammation factors. Meanwhile, we concluded the ongoing researches on novel measurements including chemical analysis, machine learning and artificial intelligence for predicting the cause of SCD.


BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.
The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6, encoding connexin30, which appear to be coordinately regulated in the inner ear. In this work, we investigated the expression and function of connexin26 and connexin30 from postnatal day 5 to adult age in double transgenic Cx26(Sox10Cre) mice, which we obtained by crossing connexin26 floxed mice with a deleter Sox10-Cre line. Cx26(Sox10Cre) mice presented with complete connexin26 ablation in the epithelial gap junction network of the cochlea, whereas connexin30 expression was developmentally delayed; immunolabeling patterns for both connexins were normal in the cochlear lateral wall. In vivo electrophysiological measurements in Cx26(Sox10Cre) mice revealed profound hearing loss accompanied by reduction of endocochlear potential, and functional experiments performed in postnatal cochlear organotypic cultures showed impaired gap junction coupling. Transduction of these cultures with a bovine adeno associated virus vector restored connexin26 protein expression and rescued gap junction coupling. These results suggest that restoration of normal connexin levels by gene delivery via recombinant adeno associated virus could be a way to rescue hearing function in DFNB1 mouse models and, in future, lead to the development of therapeutic interventions in humans.


Coupling ITO3dE model and GIS for spatiotemporal evolution analysis of agricultural non-point source pollution risks in Chongqing in China.
To determine the risk state distribution, risk level, and risk evolution situation of agricultural non-point source pollution (AGNPS), we built an 'Input-Translate-Output' three-dimensional evaluation (ITO3dE) model that involved 12 factors under the support of GIS and analyzed the spatiotemporal evolution characteristics of AGNPS risks from 2005 to 2015 in Chongqing by using GIS space matrix, kernel density analysis, and Getis-Ord Gi* analysis. Land use changes during the 10 years had a certain influence on the AGNPS risk. The risk values in 2005, 2010, and 2015 were in the ranges of 0.40-2.28, 0.41-2.57, and 0.41-2.28, respectively, with the main distribution regions being the western regions of Chongqing (Dazu, Jiangjin, etc.) and other counties such as Dianjiang, Liangping, Kaizhou, Wanzhou, and Zhongxian. The spatiotemporal transition matrix could well exhibit the risk transition situation, and the risks generally showed no changes over time. The proportions of 'no-risk no-change', 'low-risk no-change', and 'medium-risk no-change' were 10.86%, 33.42%, and 17.25%, respectively, accounting for 61.53% of the coverage area of Chongqing. The proportions of risk increase, risk decline, and risk fluctuation were 13.45%, 17.66%, and 7.36%, respectively. Kernel density analysis was suitable to explore high-risk gathering areas. The peak values of kernel density in the three periods were around 1110, suggesting that the maximum gathering degree of medium-risk pattern spots basically showed no changes, but the spatial positions of high-risk gathering areas somehow changed. Getis-Ord Gi* analysis was suitable to explore the relationships between hot and cold spots. Counties with high pollution risks were Yongchuan, Shapingba, Dianjiang, Liangping, northwestern Fengdu, and Zhongxian, while counties with low risks were Chengkou, Wuxi, Wushan, Pengshui, and Rongchang. High-value hot spot zones gradually dominated in the northeast of Chongqing, while low-value cold spot zones gradually dominated in the Midwest. Our results provide a scientific base for the development of strategies to prevent and control AGNPS in Chongqing.


Suprachoroidal hemorrhage during pars plana vitrectomy.
Suprachoroidal hemorrhage is an uncommon but serious complication of pars plana vitrectomy that can be associated with a guarded visual prognosis. Risk factors for development of suprachoroidal hemorrhage during pars plana vitrectomy include high myopia, history of previous retinal detachment surgery, rhegmatogenous retinal detachment, use of cryotherapy, scleral buckling at the time of pars plana vitrectomy, external drainage of the subretinal fluid, intraoperative systemic hypertension, and bucking during general anesthesia. In eyes with suprachoroidal hemorrhage during pars plana vitrectomy, the final visual and anatomic outcomes may be compromised by persistent retinal detachment, secondary glaucoma, and ocular hypotony. In most cases, intraoperative drainage of suprachoroidal hemorrhage is not associated with a better outcome. The prognosis is more favorable if the suprachoroidal hemorrhage is localized and does not extend in to the posterior pole.


A Massively Parallel Implementation of the CCSD(T) Method Using the Resolution-of-the-Identity Approximation and a Hybrid Distributed/Shared Memory Parallelization Model.
A parallel algorithm is described for the coupled-cluster singles and doubles method augmented with a perturbative correction for triple excitations [CCSD(T)] using the resolution-of-the-identity (RI) approximation for two-electron repulsion integrals (ERIs). The algorithm bypasses the storage of four-center ERIs by adopting an integral-direct strategy. The CCSD amplitude equations are given in a compact quasi-linear form by factorizing them in terms of amplitude-dressed three-center intermediates. A hybrid MPI/OpenMP parallelization scheme is employed, which uses the OpenMP-based shared memory model for intranode parallelization and the MPI-based distributed memory model for internode parallelization. Parallel efficiency has been optimized for all terms in the CCSD amplitude equations. Two different algorithms have been implemented for the rate-limiting terms in the CCSD amplitude equations that entail O(NO2NV4) and O(NO3NV3)-scaling computational costs, where NO and NV denote the number of correlated occupied and virtual orbitals, respectively. One of the algorithms assembles the four-center ERIs requiring NV4 and NO2NV2-scaling memory costs in a distributed manner on a number of MPI ranks, while the other algorithm completely bypasses the assembling of quartic memory-scaling ERIs and thus largely reduces the memory demand. It is demonstrated that the former memory-expensive algorithm is faster on a few hundred cores, while the latter memory-economic algorithm shows a better strong scaling in the limit of a few thousand cores. The program is shown to exhibit a near-linear scaling, in particular for the compute-intensive triples correction step, on up to 8000 cores. The performance of the program is demonstrated via calculations involving molecules with 24-51 atoms and up to 1624 atomic basis functions. As the first application, the complete basis set (CBS) limit for the interaction energy of the π-stacked uracil dimer from the S66 data set has been investigated. This work reports the first calculation of the interaction energy at the CCSD(T)/aug-cc-pVQZ level without local orbital approximation. The CBS limit for the CCSD correlation contribution to the interaction energy was found to be -8.01 kcal/mol, which agrees very well with the value -7.99 kcal/mol reported by Schmitz, Hättig, and Tew [ Phys. Chem. Chem. Phys. 2014, 16, 22167-22178]. The CBS limit for the total interaction energy was estimated to be -9.64 kcal/mol.


A double-potential ratiometric electrochemiluminescence platform based on g-C3N4 nanosheets (g-C3N4 NSs) and graphene quantum dots for Cu2+ detection.
A new kind of convenient, low-cost double-potential ratiometric ECL sensing platform for the quantification of Cu2+ was developed with carbon nitride nanosheets (g-C3N4 NSs) and graphene quantum dots (GQDs) as ECL luminophores. g-C3N4 NSs mixed with multi-walled carbon nanotubes (MWCNTs) was immobilized on a glass carbon electrode (GCE) and produced strong cathodic ECL at a potential of -1.2 V (vs. Ag/AgCl), while GQDs in the solution gave anodic ECL at +2.5 V. MWCNTs were used here to amplify the ECL signal of g-C3N4 NSs. The addition of Cu2+ causes the cathodic ECL signal from g-C3N4 to decline, while the anodic ECL signal from GQDs remains unchanged. With the anodic ECL signal as an internal reference, a double-potential ratiometric ECL sensing platform for Cu2+ was established. The ratio of the cathodic signal intensity to anodic signal intensity showed a linear response to the Cu2+ concentration over a range from 5.0 × 10-10 to 1.0 × 10-6 mol L-1 and the detection limit was 0.37 nmol L-1 (3σ/S). Such a construction strategy alleviates the interference from the environment and therefore improves the detection accuracy of Cu2+. Compared with other methods for Cu2+ detection, this method is simpler and more sensitive.


Advance directives in the trauma intensive care unit: Do they really matter?
Despite advances in the care of the injured patient, 22% of trauma patients admitted to the intensive care unit will die from their injuries. As a majority of these deaths will occur due to withdrawal of care, intensivists should be proficient in their ability to discuss end-of-life care with patients and families. While the use of advance directives to document patients' wishes has increased, their utility is uncertain. We review the effectiveness and obstacles of advance directives.


Exploiting Genomics Resources to Identify Candidate Genes Underlying Antioxidants Content in Tomato Fruit.
The tomato is a model species for fleshy fruit development and ripening, as well as for genomics studies of others Solanaceae. Many genetic and genomics resources, including databases for sequencing, transcriptomics and metabolomics data, have been developed and are today available. The purpose of the present work was to uncover new genes and/or alleles that determine ascorbic acid and carotenoids accumulation, by exploiting one Solanum pennellii introgression lines (IL7-3) harboring quantitative trait loci (QTL) that increase the content of these metabolites in the fruit. The higher ascorbic acid and carotenoids content in IL7-3 was confirmed at three fruit developmental stages. The tomato genome reference sequence and the recently released S. pennellii genome sequence were investigated to identify candidate genes (CGs) that might control ascorbic acid and carotenoids accumulation. First of all, a refinement of the wild region borders in the IL7-3 was achieved by analyzing CAPS markers designed in our laboratory. Afterward, six CGs associated to ascorbic acid and one with carotenoids metabolism were identified exploring the annotation and the Gene Ontology terms of genes included in the region. Variants between the sequence of the wild and the cultivated alleles of these genes were investigated for their functional relevance and their potential effects on the protein sequences were predicted. Transcriptional levels of CGs in the introgression region were extracted from RNA-Seq data available for the entire S. pennellii introgression lines collection and verified by Real-Time qPCR. Finally, seven IL7-3 sub-lines were genotyped using 28 species-specific markers and then were evaluated for metabolites content. These analyses evidenced a significant decrease in transcript abundance for one 9-cis-epoxycarotenoid dioxygenase and one L-ascorbate oxidase homolog, whose role in the accumulation of carotenoids and ascorbic acid is discussed. Comprehensively, the reported results demonstrated that combining genetic and genomic resources in tomato, including bioinformatics tools, was a successful strategy to dissect one QTL for the increase of ascorbic acid and carotenoids in tomato fruit.


Regulation of acetylcholinesterase expression during neuronal differentiation.
We have examined the developmental expression of acetylcholinesterase (AChE) during the process of neuronal differentiation from a pluripotent stem cell. P19 embryonic carcinoma cells form embryoid bodies, which, when cultured with retinoic acid, are induced to differentiate into neurons and glia. No AChE activity is present in the undifferentiated stem cells, and mRNA protection analyses do not detect AChE mRNA. Commitment to a neuronal differentiation pathway results in increased levels of AChE mRNA, production of a tetrameric form of the enzyme, and secretion of AChE into the culture medium. Concomitant with subsequent morphological differentiation into neurons, enzyme secretion diminishes and AChE becomes largely tethered to the neuronal cell membranes. The enzyme is attached to the cell surface as a globular tetramer. Its hydrodynamic properties are consistent with association through a noncatalytic hydrophobic subunit rather than anchorage by a glycophospholipid tail. No change in the rate of transcription of the Ache gene was detected during the course of differentiation, suggesting that the gene is actively transcribed at very early stages of development. Results suggest that stabilization of a labile mRNA governs the increase in AChE mRNA and gene product. The studies presented indicate that an early event in neuronal differentiation is the stabilization of the mRNA leading to expression of a secreted form of AChE. A subsequent step associated with neurite outgrowth results in a transition from secretion of the tetrameric enzyme to its localization on the cell membrane.


Synthesis and reactivity of palladium(II) fluoride complexes containing nitrogen-donor ligands.
This article describes the synthesis, characterization, and reactivity of palladium(II) fluoride complexes containing sp(2) and sp(3) nitrogen-containing supporting ligands. Both cis and trans complexes of general structure (N)(N')Pd(II)(R)(F) (R = Ar or CH(3)) as well as cis-(N)(2)Pd(II)(F)(2) are reported. Crystallographic characterization of these molecules has allowed structural comparisons to related phosphine-ligated species. Furthermore, these studies have revealed that nitrogen-donor ligands support some of the longest and the shortest Pd-F bonds reported to date. The thermal decomposition of (N)(N')Pd(II)(R)(F) has also been examined, and no products of C-F bond-forming reductive elimination were obtained in any case.


The individual-cell-based cryo-chip for the cryopreservation, manipulation and observation of spatially identifiable cells. II: functional activity of cryopreserved cells.
The cryopreservation and thawing processes are known to induce many deleterious effects in cells and might be detrimental to several cell types. There is an inherent variability in cellular responses among cell types and within individual cells of a given population with regard to their ability to endure the freezing and thawing process. The aim of this study was to evaluate the fate of cryopreserved cells within an optical cryo apparatus, the individual-cell-based cryo-chip (i3C), by monitoring several basic cellular functional activities at the resolution of individual cells. In the present study, U937 cells underwent the freezing and thawing cycle in the i3C device. Then a panel of vital tests was performed, including the number of dead cells (PI staining), apoptotic rate (Annexin V staining), mitochondrial membrane potential (TMRM staining), cytoplasm membrane integrity and intracellular metabolism (FDA staining), as well as post-thawing cell proliferation assays. Cells that underwent the freezing - thawing cycle in i3C devices exhibited the same functional activity as control cells. Moreover, the combination of the multi-parametric analysis at a single cell resolution and the optical and biological features of the device enable an accurate determination of the functional status of individual cells and subsequent retrieval and utilization of the most valuable cells. The means and methodologies described here enable the freezing and thawing of spatially identifiable cells, as well as the efficient detection of viable, specific, highly biologically active cells for future applications.


Characterization and expression of L-amino acid oxidase of mouse milk.
l-Amino acid oxidase (LAO) was purified from mouse milk. LAO reacted with l-amino acids in an apparent order of Phe > Met, Tyr > Cys, Leu > His other 11 amino acids tested and produced H(2)O(2) in a dose- and time-dependent manner. LAO in milk had a molecular mass of about 113 kDa and was converted to a 60-kDa protein by SDS-PAGE. LAO consisted of two subunits. The N- and C-terminal amino acid sequence determination followed by cDNA cloning showed that the 60-kDa protein consisted of 497 amino acids. LAO mRNA spanned about 2.0 kb, and its expression was found only in the mammary epithelial cells. Glucocorticoid was essential for LAO gene expression. Thus, the LAO gene is expressed acutely upon the onset of milk synthesis. LAO mRNA increased 1 day before parturition, peaked during early to mid-lactation, and decreased at the end of lactation. This is the first demonstration showing that LAO is present in milk. Mastitis is caused by an intramammary bacterial infection. As mouse milk produced H(2)O(2) using endogenous free amino acids, we suggest that LAO, together with free amino acids, is responsible for killing bacteria in the mammary gland.


Switching suicide methods as a predictor of completed suicide in individuals with repeated self-harm: a community cohort study in northern Taiwan.
Repetition of suicide attempts is common, but little is known about the relationship between switching methods of suicide attempt and the probability of completed suicide. This study aimed to determine the transition of methods chosen by individuals who repeat suicide attempts, and how the switched methods of suicide attempts influence the risk of suicide death. All consecutive individuals (n = 2052) with an episode of non-fatal suicide attempt registered in a surveillance database provided by the Department of Health of the Keelung City Government from 1 January 2006 to 31 December 2010 were enrolled and followed up until the end of 2011. The earliest attempt recorded in the database was defined as the index attempt. Data on the time of subsequent completed suicide and methods chosen for repeated self-harm during the follow-up period were analyzed by performing a Cox proportional hazards regression. Of the total subjects, 374 (18.2%) had at least one other attempted suicide and 50 (2.4%) eventually died by suicide. Subjects who used highly lethal methods in the index self-harm tended to switch methods in the next suicide attempt (p<0.001). Switching to a more lethal method was a significant predictor of completed suicide (adjusted hazard ratio (aHR) 7.05, 95% confidence interval (CI) 3.52-14.14). In addition, subjects who used charcoal-burning in the index self-harm attempt had a higher risk of subsequent suicide death (aHR 3.47, 95% CI 1.57-7.68). The findings in this study give us some insight into the patterns of methods in repeat suicide attempters. The intent behind switching methods of suicide attempt might be considered as an important item of clinical assessment of the seriousness of suicidal behavior.


The response to heat shock and oxidative stress in Saccharomyces cerevisiae.
A common need for microbial cells is the ability to respond to potentially toxic environmental insults. Here we review the progress in understanding the response of the yeast Saccharomyces cerevisiae to two important environmental stresses: heat shock and oxidative stress. Both of these stresses are fundamental challenges that microbes of all types will experience. The study of these environmental stress responses in S. cerevisiae has illuminated many of the features now viewed as central to our understanding of eukaryotic cell biology. Transcriptional activation plays an important role in driving the multifaceted reaction to elevated temperature and levels of reactive oxygen species. Advances provided by the development of whole genome analyses have led to an appreciation of the global reorganization of gene expression and its integration between different stress regimens. While the precise nature of the signal eliciting the heat shock response remains elusive, recent progress in the understanding of induction of the oxidative stress response is summarized here. Although these stress conditions represent ancient challenges to S. cerevisiae and other microbes, much remains to be learned about the mechanisms dedicated to dealing with these environmental parameters.


Discrete solitons and nonlinear surface modes in semi-infinite waveguide arrays.
We discuss the formation of self-trapped localized states near the edge of a semi-infinite array of nonlinear optical waveguides. We study a crossover from nonlinear surface states to discrete solitons by analyzing the families of odd and even modes centered at finite distances from the surface and reveal the physical mechanism of the nonlinearity-induced stabilization of surface modes.


Austerity on the frontline- a preliminary study of physiotherapists working in the National Health Service in the UK.
Organizational reform has been commonplace in the response to global socio-economic changes. Rising managerialism, consumerism and marketization has accelerated reforms; providing challenges for the healthcare professions. The latest socio-economic challenge, austerity, and its professional implications have scarcely been researched. This study aims to explore the lived reality of austerity as experienced by physiotherapists working on the frontline of the National Health Service (NHS) in the UK. Ethical approval was granted by the University of Nottingham; the study was advertised via the Chartered Society of Physiotherapy online network. Two participants took part; semi-structured interviews were completed, audio recorded, and transcribed. Data was analyzed using thematic analysis. Three themes arose from the data: (1) Fulfilling professional responsibilities; (2) Changing organizational landscape; and (3) Professional reality of rationalizing and accommodating austerity. The clinical implications of austerity included increased length of hospital stay, insufficient community services, constrained resources, and understaffing. Participants demonstrated attempts to preserve their professional status and services through restratification throughout the intra-professional hierarchy, changing division of labor, and re-professionalization. Despite claims that austerity is coming to an end, it remained a reality for these clinicians in the NHS. Physiotherapists in this study used similar methods to preserve practice when faced with exogenous constraints as seen in medicine, such as re-professionalization and restratification. However, this attempt to defend professionalism by a non-medical healthcare profession was met with both successes and losses and has implications for the wider healthcare profession ecology, identifying an area for future research.


Clinical screening for obsessive-compulsive and related disorders.
Obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD) and other OCD-related disorders (OCDs) are frequently overlooked during medical or even psychiatric evaluation. Individuals with affective disorders, anxiety disorders, eating disorders, alcohol abuse and schizophrenia are commonly affected. Increased prevalence of OCDs is also reported to occur in certain secondary health-care settings. Better identification and treatment of OCDs are increasingly recognized as important public health priorities. In this narrative review we consider the arguments for the use of screening strategies for OCD in clinical practice, paying particular attention to pragmatic issues such as the shortage of suitable screening instruments and areas of medical practice where screening might most profitably be exercised. Arguments for screening in fields where affected individuals congregate appear persuasive, although evidence that screening produces clinical and social benefits by reducing morbidity is still lacking. Confirmation of health-care settings attracting high concentrations of OCD and BDD and evaluation of specific screening instruments and their utility in reducing the burden of disease are important areas for future research. Further evaluation of the validity and reliability of specific screening tools across different clinical populations is required.


[Application of the thoraco-umbilical flap for the repair of large infected wounds on the limb].
We have repaired large infected wounds on the limb in 18 cases using the thoraco-umbilical flap. Of them, 6 were island flaps and 12 were free flaps. The size of the flap ranged from 10 cm x 12 cm, to 10 cm x 40 cm. All flaps survived. The advantages of the flap were (1) rich blood supply providing good anti-infection property; (2) the muscle carried by the flap could be used to fill a bone cavity, aiding to cure osteomyelitis; (3) the flap could be made rather big and has long vascular pedicle that was flexible for transferring.


Nitinol micro-forceps for retrieval of intravascular objects: first in vitro experiences.
With the progress of interventional procedures the need for retrieval of iatrogenic materials increases. Here we introduce a new nitinol micro-forceps for retrieval of intravascular objects and report our first in-vitro experiences. In a tube model simulating arterial anatomy a total of eight endovascular coils were removed from the "carotid artery" using a "trans-femoral" approach. Additionally, the withdrawal of grasped coils through vascular sheaths of F-5, F-6, F-8, F-12 was observed (n = 4/seize). Seven of 8 coils were successfully grasped. Loss of one coil occurred during retrieval. Withdrawal of coils through a vascular sheath was possible only when the coil was grasped at one of its ends. The nitinol micro-forceps proved to be a potential tool in endovascular retrieval of foreign objects especially in small caliber vessels. However, further technical modifications are necessary to improve maneuverability and grasping strength.


Effects of atrial pacing, isoprenaline and lignocaine on experimental polymorphous ventricular tachycardia.
In 22 anaesthetised dogs, iv, administration of quinidine sulphate (30 mg X kg-1) over 5 min produced bradycardia and marked prolongation of the QT interval. Right ventricular extrastimulations, four times diastolic threshold, provoked polymorphous ventricular tachycardia in 18 dogs, and typical torsade de pointes was observed in four of these 18 dogs. Ventricular flutter was induced in another four dogs. In one of these 22 dogs, double stimuli were required to induce ventricular tachyarrhythmias, in 19 dogs triple stimuli, and in two dogs quadruple stimuli. Using this experimental model, effects of interventions including atrial pacing, isoprenaline, and lignocaine on the QT interval and induction of polymorphous ventricular tachycardia by extrastimuli were studied. Atrial pacing shortened QT interval only slightly and did not prevent induction of polymorphous ventricular tachycardia in nine dogs studied. Isoprenaline infusion definitely shortened QT interval, and in four out of nine dogs triple stimuli could not elicit polymorphous ventricular tachycardia. By contrast, although the QT interval was not shortened, lignocaine was effective in preventing induction of polymorphous ventricular tachycardia by triple stimuli in three out of nine dogs. These results indicate atrial pacing is an ineffective means of preventing induction of polymorphous ventricular tachycardia by extrastimuli in dogs with a long QT interval, but that isoprenaline and lignocaine are effective in some dogs.


Synthetic PMMA-grafted polysaccharides as hydrophilic matrix for controlled-release forms.
This paper describes the rheological behavior of starch and cellulose acrylic graft copolymers synthesized with the aim of obtaining controlled-release excipients. The rheological characteristics determine the final release properties of matrix tablets. The study of the storage and loss moduli (G' and G", respectively) and the viscosity allowed us to know if the polymer behavior was that of a gel and, hence, if it could act as a barrier to drug diffusion. Since dynamic measurements showed a storage modulus higher than the loss modulus, we assessed that all the polymers were gels. Thus, knowing that all the graft copolymers had acceptable properties for compression, the release of theophylline as a model drug at different pH was studied. Polymers with higher absorption capacity, viscosity, and compactibility allowed formulations with slower release rates.


A CASPT2 and CASSCF approach to the cycloaddition of ketene and imine: a new mechanistic scheme of the Staudinger reaction.
We report a new theoretical study of the mechanism of the parent Staudinger reaction between ketene and formaldimine. This mechanism, in contrast with previously reported computational studies, involves the formation of two different intermediates, gauche and trans, which can be interconnected on the potential energy surface depending upon reaction conditions. This novel CASPT2/CASSCF mechanistic scheme may be considered a new starting point to rationalize stereochemical outcome and solvent effects in these reactions.


Rhinothermy delivered by nasal high flow therapy in the treatment of the common cold: a randomised controlled trial.
The common cold is the most common infectious disease affecting humans and has a substantial economic impact on society. Human rhinoviruses, which cause almost two-thirds of colds, have demonstrated temperature-dependent replication which is optimal between 33°C and 35°C. This randomised, single-blind, parallel-group trial completed at a single-centre in New Zealand, recruited 170 participants aged 18-75 years (mean age 27.5 years) who were within 48 hours of common cold symptom onset and had a symptom score (the Modified Jackson Score (MJS)) ≥7 and a negative point-of-care test for influenza. Participants were blinded to the intervention and randomised (1:1) to 5 days of either nasal high flow rhinothermy (rNHF) (100% humidified air delivered at 35 L/min and 41°C for 2 hours daily) (n=85) or 'sham' rhinothermy (100% humidified air delivered at 10 L/min and 31°C for 10 min daily) (n=85) and completed daily symptom diaries, which included the MJS, for 14 days, to investigate whether rNHF reduced common cold symptom severity and duration compared with 'sham' rhinothermy. An intention-to-treat superiority analysis included all randomised participants and showed no difference between treatment groups for the primary outcome, the day 4 MJS analysed by analysis of covariance: mean (SD) 6.33 (3.97) for rNHF vs 5.8 (3.15) for 'sham'; estimated difference (95% CI) 0.37 (-0.69 to 1.42), p=0.49. There was no difference in time until resolution of symptoms: mean (SD) 5.96 (4.47) days for rNHF vs 6.42 (4.09) days for 'sham'; estimated difference (95% CI) 1.02 (0.75 to 1.38), p=0.91. There were no serious adverse events related to the study treatments. This well-powered, single-blind randomised controlled trial does not provide evidence that 5 days of rNHF (100% humidified air heated to 41°C delivered at 35 L/min for 2 hours daily) reduces common cold symptom severity or duration. However, investigation of rNHF in the treatment of influenza is warranted. ACTRN12617001340325.


ProMACE-MOPP vs MACOP-B in high grade non-Hodgkin's lymphomas: a randomised study in a multicenter cooperative study group (NHLCSG).
From January '85 to April '87, 81 patients (pts) with diffuse intermediate and high-grade non-Hodgkin's lymphomas were treated with the ProMace/MOPP protocol in a large Italian Cooperative Study Group (NHLCSG). Criteria for entry into the study included: no prior therapy, stage III-IV or stage II with bulky disease and/or B-symptoms, age below 65. 79 pts were evaluable for response. Almost all pts received six courses of chemotherapy, plus radiotherapy on bulky disease. 53 pts (67%) achieved complete remission (CR), 7 (9%) partial remission (PR), 4 (5%) were considered stable disease (SD) and 15 (19%) progression disease (PD) with 5 of them died early during treatment. The actuarial overall survival (OS) and disease free survival (DFS) are respectively 54% at 61 mos and 62% at 41 mos. The median follow-up from the end of therapy is 56 mos (range 40-68). Until now 20 pts (38%) relapsed on a median time of 8 mos (range 2-21) from CR. These data allowed to us to consider this regimen as effective as the third generation protocols also taking into account the multicenter basis of this study. With the aim to evaluate the impact of the third generation regimen on the outcome of these pts, a randomized study has been performed comparing ProMACE-MOPP with the third generation regimens MACOP-B. Therefore, from 1988 up to now, 206 pts with similar clinical and histological characteristics, have been enrolled in the two arms. No differences in terms of CR and DFS have been registered between the two treatments, with roughly the same toxicity. An analysis of prognostic factors in the larger series of pts treated with ProMACE-MOPP in the first and in the second study (167 pts) was performed. On these basis it seems reasonable that our next step would be to candidate these poor prognosis pts to a new therapeutic strategy which included the use of ABMT and/or PBSC transplantation as first line.


Sugar-metal ion interactions: the complicated coordination structures of cesium ion with D-ribose and myo-inositol.
The novel cesium chloride-D-ribose complex (CsCl·C5H10O5; Cs-R) and cesium chloride-myo-inositol complex (CsCl·C6H12O6; Cs-I) have been synthesized and characterized using X-ray diffraction and FTIR, FIR, THz, and Raman spectroscopy. Cs(+) is eight-coordinated to three chloride ions, O1 and O2 from one D-ribose molecule, O1 from another D-ribose molecule, and O4 and O5 from the third D-ribose molecule in Cs-R. For one D-ribose molecule, the oxygen atom O1 in the ring is coordinated to two cesium ions as an oxygen bridge, O2 is cocoordinated with O1 to one of the two cesium ions, and O4 and O5 are coordinated to the third cesium ion, respectively. O3 does not coordinate to metal ions and only takes part in forming hydrogen bonds. One chloride ion is connected to three cesium ions. Thus, a complicated structure of Cs-D-ribose forms. For Cs-I, Cs(+) is 10-coordinated to three chloride ions, O1 and O2 from one myo-inositol molecule, O3 and O4 from another myo-inositol molecule, O5 and O6 from the third myo-inositol molecule, and O6 from the fourth myo-inositol molecule. One metal ion is connected to four ligands, and one myo-inositol is coordinated to four Cs(+) ions, which is also a complicated coordination structure. Crystal structure results, FTIR, FIR, THz, and Raman spectra provide detailed information on the structure and coordination of hydroxyl groups to metal ions in the cesium chloride-D-ribose and cesium chloride-myo-inositol complexes.


Association of synapsin 2 with schizophrenia in families of Northern European ancestry.
The synapsin 2 (Syn2) gene (3p25) is implicated in synaptogenesis, neurotransmitter release, and the localization of nitric oxide synthase to the proximity of its targets. In this study we investigated linkage and association between the Syn2 locus and schizophrenia. 37 pedigrees of Northern European ancestry from the NIMH Human Genetics Initiative collection were used. Four microsatellites and twenty SNPs were genotyped. Linkage (FASTLINK) and association (TRANSMIT, PDTPHASE) between markers and schizophrenia were evaluated. A maximum heterogeneity LOD of 1.93 was observed at marker D3S3434 with a recessive mode of inheritance. Significant results were obtained for association with schizophrenia using TRANSMIT (minimum nominal p=0.0000005) and PDTPHASE (minimum nominal p=0.014) using single marker analyses. Haplotype analysis using markers in introns 5 and 6 of Syn2 provided a single haplotype that is significantly associated with schizophrenia using TRANSMIT (nominal p<0.00000001) and PDTPHASE (nominal p=0.02). Simulation studies confirm the global significance of these results, but demonstrate that the small p-values generated by the bootstrap routine of TRANSMIT can be consistently anticonservative. Review of the literature suggests that Syn2 is likely to be involved in the etiology or pathogenesis of schizophrenia.


Animal models for AIDS.
Animal models will play a central role in AIDS research in the coming years. Important models for human immunodeficiency virus (HIV)-induced disease in humans include HIV-infected great apes, simian immunodeficiency virus-infected Asian monkeys and infections of ungulates and cats with HIV-related lentiviruses. The nature of the diseases induced by these viruses are described here by Norman Letvin, emphasizing aspects with particular relevance to human HIV infections.


Bromeliad catchments as habitats for methanogenesis in tropical rainforest canopies.
Tropical epiphytic plants within the family Bromeliaceae are unusual in that they possess foliage capable of retaining water and impounded material. This creates an acidic (pH 3.5-6.5) and anaerobic (<1 ppm O(2)) environment suspended in the canopy. Results from a Costa Rican rainforest show that most bromeliads (n = 75/86) greater than ~20 cm in plant height or ~4-5 cm tank depth, showed presence of methanogens within the lower anoxic horizon of the tank. Archaea were dominated by methanogens (77-90% of recovered ribotypes) and community structure, although variable, was generally comprised of a single type, closely related to either hydrogenotrophic Methanoregula or Methanocella, a specific clade of aceticlastic Methanosaeta, or Methanosarcina. Juvenile bromeliads, or those species, such as Guzmania, with shallow tanks, generally did not possess methanogens, as assayed by polymerase chain reaction specific for methanogen 16S rRNA genes, nor did artificial catchments (~100 ml volume), in place 6-12 months prior to sample collection. Methanogens were not detected in soil (n = 20), except in one case, in which the dominant ribotype was different from nearby bromeliads. Recovery of methyl coenzyme M reductase genes supported the occurrence of hydrogenotrophic and aceticlastic methanogens within bromeliad tanks, as well as the trend, via QPCR analysis of mcrA, of increased methanogenic capacity with increased plant height. Methane production rates of up to 300 nmol CH(4) ml tank water(-1) day(-1) were measured in microcosm experiments. These results suggest that bromeliad-associated archaeal communities may play an important role in the cycling of carbon in neotropical forests.


Effect of brain-computer interface training based on non-invasive electroencephalography using motor imagery on functional recovery after stroke - a systematic review and meta-analysis.
Training with brain-computer interface (BCI) technology in the rehabilitation of patients after a stroke is rapidly developing. Numerous RCT investigated the effects of BCI training (BCIT) on recovery of motor and brain function in patients after stroke. A systematic literature search was performed in Medline, IEEE Xplore Digital Library, Cochrane library, and Embase in July 2018 and was repeated in March 2019. RCT or controlled clinical trials that included BCIT for improving motor and brain recovery in patients after a stroke were identified. Data were meta-analysed using the random-effects model. Standardized mean difference (SMD) with 95% confidence (95%CI) and 95% prediction interval (95%PI) were calculated. A meta-regression was performed to evaluate the effects of covariates on the pooled effect-size. In total, 14 studies, including 362 patients after ischemic and hemorrhagic stroke (cortical, subcortical, 121 females; mean age 53.0+/- 5.8; mean time since stroke onset 15.7+/- 18.2 months) were included. Main motor recovery outcome measure used was the Fugl-Meyer Assessment. Quantitative analysis showed that a BCI training compared to conventional therapy alone in patients after stroke was effective with an SMD of 0.39 (95%CI: 0.17 to 0.62; 95%PI of 0.13 to 0.66) for motor function recovery of the upper extremity. An SMD of 0.41 (95%CI: - 0.29 to 1.12) for motor function recovery of the lower extremity was found. BCI training enhanced brain function recovery with an SMD of 1.11 (95%CI: 0.64 to 1.59; 95%PI ranging from 0.33 to 1.89). Covariates such as training duration, impairment level of the upper extremity, and the combination of both did not show significant effects on the overall pooled estimate. This meta-analysis showed evidence that BCI training added to conventional therapy may enhance motor functioning of the upper extremity and brain function recovery in patients after a stroke. We recommend a standardised evaluation of motor imagery ability of included patients and the assessment of brain function recovery should consider neuropsychological aspects (attention, concentration). Further influencing factors on motor recovery due to BCI technology might consider factors such as age, lesion type and location, quality of performance of motor imagery, or neuropsychological aspects. PROSPERO registration: CRD42018105832 .


Two regions of EpsL involved in species-specific protein-protein interactions with EpsE and EpsM of the general secretion pathway in Vibrio cholerae.
Extracellular secretion of proteins via the type II or general secretion pathway in gram-negative bacteria requires the assistance of at least 12 gene products that are thought to form a complex apparatus through which secreted proteins are translocated. Although this apparatus is specifically required only for the outer membrane translocation step during transport across the bacterial cell envelope, it is believed to span both membranes. The EpsE, EpsL, and EpsM proteins of the type II apparatus in Vibrio cholerae are thought to form a trimolecular complex that is required to either control the opening and closing of the secretion pore or to transduce energy to the site of outer membrane translocation. EpsL is likely to play an important role in this relay by interacting with both the cytoplasmic EpsE protein and the cytoplasmic membrane protein EpsM, which is predominantly exposed on the periplasmic side of the membrane. We have now extended this model and mapped the separate regions within EpsL that contain the EpsE and EpsM binding domains. By taking advantage of the species specificity of the type II pathway, we have used chimeric proteins composed of EpsL and its homologue, ExeL, from Aeromonas hydrophila together with either EpsE or its Aeromonas homologue, ExeE, to complement the secretion defect in both epsL and exeL mutant strains. These studies have mapped the species-specific EpsE binding site to the N-terminal cytoplasmic region between residues 57 and 216 of EpsL. In addition, the species-specific EpsM binding site was mapped to the C-terminal half of EpsL by coimmunoprecipitation of EpsM with different EpsL-ExeL chimeras. This site is present in the region between amino acids 216 and 296, which contains the predicted membrane-spanning segment of EpsL.


Public Support for E-Cigarette-related Policies among a Nationally Representative Sample of US Adults.
The wide availability of flavored e-cigarettes and broad use of e-cigarettes in public places may contribute to the rapidly increasing rates of use among youth and young adults in the U.S. However, policies at the federal, state and local levels can address these factors. Assess public support for 5 e-cigarette-related policies and evaluate response patterns by demographics, tobacco use, e-cigarette harm perceptions, geographic region, and strength of state-level clean indoor air policies. Data were collected Oct-Dec 2018 from a nationally representative online panel of U.S. adults (n = 3211). We measured support for 5 policies: (1) a ban on the sale flavored e-cigarettes; (2) requiring tobacco products, like e-cigarettes, be kept out of view in stores where adolescents shop; and prohibiting e-cigarette use in (3) all public places; (4) restaurants; and (5) bars. Weighted, adjusted logistic regressions modeled variation in policy support. A majority of respondents (63.3%) supported a flavor ban, with no differences in support by smoking status. Most respondents supported keeping tobacco products out of view (78.0%) and prohibiting e-cigarette use in indoor public places (82.9%), restaurants (86.5%), and bars (76.1%). In the adjusted models, current e-cigarette users had significantly lower odds of policy support compared to never users. We observed no differences in support by geographic region or strength of state-level clean indoor air policies. Results suggest high levels of public support to regulate e-cigarette flavors, marketing, and use in public places. Targeted messaging may be needed to increase support among current e-cigarette users.


A Web-Based App for Emotional Management During the COVID-19 Pandemic: Platform Development and Retrospective Analysis of its Use Throughout Two Waves of the Outbreak in Spain.
Quarantines and nationwide lockdowns implemented for containing the spread of the COVID-19 pandemic may lead to distress and increase the frequency of anxiety and depression symptoms among the general population. During the nationwide lockdown of the first wave of the COVID-19 outbreak in Spain, we developed and launched a web-based app to promote emotional self-care in the general population and facilitate contact with health care professionals. This study aimed to describe a web-based app and analyze its utilization pattern throughout 2 successive waves of the COVID-19 outbreak in Spain. Our web-based app targeted all individuals aged 18 years or more and was designed by adapting the contents of a mobile app for adjuvant treatment of posttraumatic stress disorder (ie, the PTSD Coach app) to the general population and the pandemic or lockdown scenario. We retrospectively assessed the utilization pattern of the web-based app using data systematically retrieved from Google Analytics. Data were grouped into 3 time periods, defined using Joinpoint regression analysis of COVID-19 incidence in our area: first wave, between-wave period, and second wave. The resulting web-based app, named gesioemocional.cat, maintains the navigation structure of the PTSD Coach app, with three main modules: tools for emotional self-care, a self-assessment test, and professional resources for on-demand contact. The self-assessment test combines the Patient Health Questionnaire-2 and the 7-item Generalized Anxiety Disorder scale and offers professional contact in the advent of a high level of depression and anxiety; contact is prioritized in accordance with a screening questionnaire administered at the time of obtaining individual consent to be contacted. The tools for emotional self-care can be accessed either on-demand or symptom-driven. The utilization analysis showed a high number of weekly accesses during the first wave. In this period, press releases regarding critical events of the pandemic progression and government decisions on containment measures were followed by a utilization peak, irrespective of the sense (ie, positive or negative) of the information. Positive information pieces (eg, relaxation of containment measures due to a reduction of COVID-19 cases) resulted in a sharp increase in utilization immediately after information release, followed by a successive decline in utilization. The second wave was characterized by a lower and less responsive utilization of the web-based app. mHealth tools may help the general population cope with stressful conditions associated with the pandemic scenario. Future studies shall investigate the effectiveness of these tools among the general population-including individuals without diagnosed mental illnesses-and strategies to reach as many people as possible.


Lumbar corsets can decrease lumbar motion in golf swing.
Swinging a golf club includes the rotation and extension of the lumbar spine. Golf-related low back pain has been associated with degeneration of the lumbar facet and intervertebral discs, and with spondylolysis. Reflective markers were placed directly onto the skin of 11young male amateur golfers without a previous history of back pain. Using a VICON system (Oxford Metrics, U.K.), full golf swings were monitored without a corset (WOC), with a soft corset (SC), and with a hard corset (HC), with each subject taking 3 swings. Changes in the angle between the pelvis and the thorax (maximum range of motion and angular velocity) in 3 dimensions (lumbar rotation, flexion-extension, and lateral tilt) were analyzed, as was rotation of the hip joint. Peak changes in lumbar extension and rotation occurred just after impact with the ball. The extension angle of the lumbar spine at finish was significantly lower under SC (38°) or HC (28°) than under WOC (44°) conditions (p < 0.05). The maximum angular velocity after impact was significantly smaller under HC (94°/sec) than under SC (177°/sec) and WOC (191° /sec) conditions, as were the lumbar rotation angles at top and finish. In contrast, right hip rotation angles at top showed a compensatory increase under HC conditions. Wearing a lumbar corset while swinging a golf club can effectively decrease lumbar extension and rotation angles from impact until the end of the swing. These effects were significantly enhanced while wearing an HC. Key pointsRotational and extension forces on the lumbar spine may cause golf-related low back painWearing lumbar corsets during a golf swing can effectively decrease lumbar extension and rotation angles and angular velocity.Wearing lumbar corsets increased the rotational motion of the hip joint while reducing the rotation of the lumbar spine.


Effects of ipriflavone on bone augmentation within a titanium cap in rabbit calvaria.
Ipriflavone (7-isopropoxyisoflavone, IP), a drug used in the treatment of osteoporosis, may promote bone formation during bone remodeling. IP has been shown to accelerate both the activity of, and formation of mineralized nodules by a human osteosarcoma cell line at an early stage. However, the direct effects of IP on bone augmentation have not been investigated. The purpose of this study was to determine whether IP induces bone augmentation within a titanium cap in rabbit calvaria at an early stage. Five adult male Japanese white rabbits were used. One cap (test site) was packed with IP in a collagen gel, and the other (control site) was packed with the collagen gel alone. After the one- and three-month healing periods, we measured the newly generated tissue and bone within the titanium caps. The amount of newly generated tissue within the titanium caps of the control sites was higher than the tests sites after one month and three months. However, the percentage of newly generated bone/bone marrow in the newly generated tissue at the test sites was higher than for the control sites after one month and three months. These results suggest that IP affects the quality of bone augmentation at an early stage.


Sub-Doppler resolution limited Lamb-dip spectroscopy of NO with a quantum cascade distributed feedback laser.
A quantum cascade distributed feedback laser operating at 5.2 microm is used to obtain sub-Doppler resolution limited saturation features in a Lamb-dip experiment on the R(13.5)1/2 and R(13.5)3/2 transitions of NO. The dips appear as transmission spikes with full widths of ~ 4.3 MHz. At this resolution the 73 MHz _-doubling of the R(13.5)3/2 line, which is normally obscured by the 130 MHz Doppler broadening, is easily resolved.


Evaluation of the Effect of PEGylated Single-Walled Carbon Nanotubes on Viability and Proliferation of Jurkat Cells.
Among the numerous nanosized drug delivery systems currently under investigation, carbon nanotubes (CNTs), regardless of being single or multiple-walled, offer several advantages and are considered as promising candidates for drug targeting. Despite the valuable potentials of CNTs in drug delivery, their toxicity still remains an important issue. After the PEGylation of single-walled CNTs (SWCNTs) with phospholipid-PEG (Pl-PEG) conjugates to prepare water-dispersible nanostructures, the present study was designed to evaluate whether the functionalization with Pl-PEG derivatives could alter the cytotoxic response of cells in culture, affect their viability and proliferation. In-vitro cytotoxicity screens were performed on cultured Jurkat cells. The SWCNTs samples used in this exposure were pristine SWCNTs, Pl-PEG 2000/5000-SWCNTs at various concentrations. Jurkat cells were first incubated for 3 h at 37°C with test materials and seeded in 6-well culture plates at a given concentration. The plates were then incubated for 24, 48 and 72 h at 37°C in a 5% CO2 humidified incubator. Cell Viability and proliferation assay were performed using trypan blue exclusion test and the cell cycle kinetic status of Jurkat cells was analyzed by flow cytometry. Cell morphology was finally studied using double staining technique and a fluorescence microscope. We found that, regardless of the duration of exposure, functionalized SWCNTs were substantially less toxic, compared to pure SWCNTs and that the molecular weight of Pl-PEGs played an important role at higher concentrations. In conclusion, our noncovalent protocol seemed to be effective for increasing SWCNTs biocompatibility.


In vivo visualization of bonghan ducts inside blood vessels of mice by using an Alcian blue staining method.
An in vivo method using Alcian blue (AB) was developed for visualizing floating threadlike tissues inside blood vessels of mice. These novel structures called intravascular Bonghan ducts (IBHDs) are considered as extension of acupuncture meridians. For in vivo imaging of IBHDs, AB solution (pH 7.4) that stains mucopolysaccharides like hyaluronic acid was used. After injecting AB solution into the femoral vein of a mouse, the threadlike structures, stained deep blue, inside the inferior vena cava. The histological results, such as hematoxylin, eosin, and AB staining, show the compositions of the cells and the extracellular matrix in the IBHD. Further studies are needed to investigate their physiological functions, especially in relation with those of other circulatory systems.


Chromatographic enantioseparation of amino acids using a new chiral stationary phase based on a macrocyclic glycopeptide antibiotic.
The separation of the enantiomers of several a-amino acids was studied on a new chiral stationary phase (CSP) which is based on the macrocyclic glycopeptide antibiotic eremomycin attached to silica particles. Retention and separation factors were determined under analytical conditions at ambient temperature for different mobile phase compositions. In order to evaluate the potential with respect to preparative separations the adsorption isotherms of D- and L-methionine were determined for one mobile phase composition applying the elution by characteristic point method. The isotherms were validated by comparing experimentally determined elution profiles with predictions based on the equilibrium dispersive model. Finally, the performance of the eremomycin CSP was compared with a commercially available CSP based on the macrocyclic antibiotic teicoplanin. After determining the isotherms of D- and L-methionine also for the teicoplanin phase, the equilibrium dispersive model was used for both CSP to identify optimal operating conditions. For the separation and conditions considered the new eremomycin CSP revealed a better performance compared to the teicoplanin CSP.


Protein kinase CK2 and ion channels (Review).
Protein kinase CK2 appears as a tetramer or higher molecular weight oligomer composed of catalytic CK2α, CK2α' subunits and non-catalytic regulatory CK2β subunits or as individual subunits. It is implicated in a variety of different regulatory processes, such as Akt signalling, splicing and DNA repair within eukaryotic cells. The present review evaluates the influence of CK2 on ion channels in the plasma membrane. CK2 phosphorylates platform proteins such as calmodulin and ankyrin G, which bind to channel proteins for a physiological transport to and positioning into the membrane. In addition, CK2 directly phosphorylates a variety of channel proteins directly to regulate opening and closing of the channels. Thus, modulation of CK2 activities by specific inhibitors, by siRNA technology or by CRISPR/Cas technology has an influence on intracellular ion concentrations and thereby on cellular signalling. The physiological regulation of the intracellular ion concentration is important for cell survival and correct intracellular signalling. Disturbance of this regulation results in a variety of different diseases including epilepsy, heart failure, cystic fibrosis and diabetes. Therefore, these effects should be considered when using CK2 inhibition as a treatment option for cancer.


Effects of a regular exercise program on biochemical parameters of type 2 diabetes mellitus patients.
We aimed to investigate the effects of a regular exercise program on exercise capacity, blood biochemical profiles, certain antioxidant and oxidative stress parameters of type 2 Diabetes mellitus (DM) patients. Thirty one type 2 DM patients (ages ranging from 42-65 years) who have hemoglobin A1c (HbA1c) levels ≥7.5% and ≤9.5% were included to study and performed two cardiopulmonary exercise tests (CPET) before and after the exercise program. Subjects performed aerobic exercise training for 90 minutes a day; 3 days a week during 12 weeks. Blood samples were collected to analyze certain oxidant and antioxidant parameters (advanced oxidation protein products [AOPP], ferric reducing ability of plasma [FRAP], malondialdehyde [MDA], and sialic acid [SA]), blood lipid profile, fasting blood glucose (FBG) and HbA1c. At the end of the program HbA1c and FBG, triglyceride (TG) and very-low-density lipoprotein (VLDL) levels decreased and high-density lipoprotein (HDL) increased significantly (P=0.000, P=0.001, P=0.008, P=0,001 and P=0.02, respectively). AOPP, FRAP, SA levels of the patients increased significantly following first CPET (P=0.000, P=0.049, P=0.014 respectively). At the end of the exercise program AOPP level increased significantly following last CPET. Baseline SA level increased significantly following exercise program (P=0.002). We suggest that poor glycemic control which plays the major role in the pathogenesis of DM and its complications would be improved by 12 weeks of a regular exercise program. Whereas the acute exercise induces protein oxidation, regularly aerobic training may enhance the antioxidant status of type 2 DM patients.


Development and Optimization of a Thrombin Sandwich Aptamer Microarray.
A sandwich microarray employing two distinct aptamers for human thrombin has been optimized for the detection of subnanomolar concentrations of the protein. The aptamer microarray demonstrates high specificity for thrombin, proving that a two-site binding assay with the TBA1 aptamer as capture layer and the TBA2 aptamer as detection layer can ensure great specificity at times and conditions compatible with standard routine analysis of biological samples. Aptamer microarray sensitivity was evaluated directly by fluorescent analysis employing Cy5-labeled TBA2 and indirectly by the use of TBA2-biotin followed by detection with fluorescent streptavidin. Sub-nanomolar LODs were reached in all cases and in the presence of serum, demonstrating that the optimized aptamer microarray can identify thrombin by a low-cost, sensitive and specific method.


Utility of combined (18)F-fluorodeoxyglucose-positron emission tomography and computed tomography in patients with cervical metastases from unknown primary tumors.
(18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) has been reported to identify primary tumors in patients with cervical metastases from cancer of unknown primary (CUP). However, few reports have assessed the use of combined FDG-PET/computed tomography (CT) in this setting. We therefore examined the utility of combined FDG-PET/CT in the detection of primary tumors and unrecognized metastases in these patients. Patients with previously untreated CUPs underwent head and neck CT and whole-body FDG-PET/CT before panendoscopy and guided biopsy. The diagnostic accuracy of CT and FDG-PET/CT in detecting primary tumors and cervical metastases was compared with that of histopathology. The ability of FDG-PET/CT to detect distant metastases was also tested. Of the 44 eligible patients, 16 had occult primary tumors in the head and neck. FDG-PET/CT was significantly more sensitive than CT for detecting primary tumors (87.5% vs. 43.7%, P=.016), but their specificity did not differ (82.1% vs. 89.3%, P=.500). Thirty-four of 44 patients underwent neck dissection; 67 of 182 dissected cervical levels had metastatic nodal diseases. On a level-by-level basis, FDG-PET/CT was significantly more sensitive than CT (94.0% vs. 71.6%, P<.001), but the two methods were equally specific (94.8% vs. 96.5%). FDG-PET/CT correctly detected distant metastases in 6 of 6 patients. Combined FDG-PET/CT is a useful screening method for primary tumor detection, accurate nodal staging, and distant metastases in patients with CUPs.


Reduction of Dental Caries Among Children and Adolescents From a 15-Year Community Water Fluoridation Program in a Township Area, Korea.
Since 2000, a community water fluoridation program (CWFP) has been implemented in Hapcheon for over 15 years. We aimed to evaluate the caries-reducing effect on permanent teeth after this implementation. In 2015, evaluation surveys were conducted by our study group, 498 subjects aged 8, 10, 12, and 15 years. As the control, 952 similarly aged subjects were selected from the Sixth Korean National Health and Nutrition Examination Survey (2013-2015 KNHANES). Data of a prospective cohort of 671 8-,10- and 12-year-olds, collected when CWFP started, were used for the evaluation. Caries-reducing effects were estimated by decayed, missing and filled teeth (DMFT) scores between CWFP and control groups, pre- and post-program. Confounders including the mean number of sealant teeth and gender were adjusted for. The mean adjusted DMFT scores of 10-, 12- and 15-year-olds in Hapcheon were significantly lower compared to KNHANES DMFT scores; in addition, those of 8-, 10- and 12-year-olds after the 15-year CWFP were significantly lower than in 2000. The caries-reducing effect among 12-year-olds was 37.6% compared to those recorded in KNHANES, and 67.4% compared to those in 2000. In conclusion, the caries-reducing effect was so high that health policy makers should consider CWFP as a priority policy for caries-reducing in Korean children and adolescents.


Shear wave elastography of lymph nodes in dogs with head and neck cancer: A pilot study.
Shear wave elastography (SWE) is a novel ultrasound imaging technique, used in human medicine to differentiate metastatic from non-metastatic lymph nodes (LNs) based on higher tissue stiffness. The objective of this pilot study was to evaluate whether canine metastatic LNs were stiffer compared to non-metastatic LNs. SWE of sentinel or regional LNs in dogs with head and neck cancer was performed. Ten elastograms of each LN were acquired. In each elastogram, mean, median, and maximum shear wave velocities (SWVs) were calculated in the most elastic region, the stiffest region, and the entire LN. The means of those SWVs for each region of each LN were subsequently calculated. Furthermore, a stepwise subsampling was performed to assess the effect of the number of acquired elastograms on the consistency of the classification of a LN as metastatic or not. Twenty-four LNs in 15 dogs with head and neck cancer were included, of which 10 LNs were metastatic. Metastatic medial retropharyngeal and mandibular LNs were successfully distinguished from non-metastatic LNs based on higher mean and median SWVs in the stiffest region and higher maximum SWVs in entire LNs. Furthermore, maximum SWVs in the stiffest region of mandibular LNs were higher in metastatic LNs compared to non-metastatic LNs. Downstream analyses demonstrated that at least eight elastograms were necessary to perform reliable analyses. This pilot trial demonstrated that SWE has potential to discriminate metastatic from non-metastatic LNs; however, LN status should be based on at least eight elastograms in future clinical trials.


Generalized Synthetic Strategy for Transition-Metal-Doped Brookite-Phase TiO2 Nanorods.
We report a generalized wet-chemical methodology for the synthesis of transition-metal (M)-doped brookite-phase TiO2 nanorods (NRs) with unprecedented wide-range tunability in dopant composition (M = V, Cr, Mn, Fe, Co, Ni, Cu, Mo, etc.). These quadrangular NRs can selectively expose {210} surface facets, which is induced by their strong affinity for oleylamine stabilizer. This structure is well preserved with variable dopant compositions and concentrations, leading to a diverse library of TiO2 NRs wherein the dopants in single-atom form are homogeneously distributed in a brookite-phase solid lattice. This synthetic method allows tuning of dopant-dependent properties of TiO2 nanomaterials for new opportunities in catalysis applications.


Automated electrotransformation of Escherichia coli on a digital microfluidic platform using bioactivated magnetic beads.
This paper reports on the use of a digital microfluidic platform to perform multiplex automated genetic engineering (MAGE) cycles on droplets containing Escherichia coli cells. Bioactivated magnetic beads were employed for cell binding, washing, and media exchange in the preparation of electrocompetent cells in the electrowetting-on-dieletric (EWoD) platform. On-cartridge electroporation was used to deliver oligonucleotides into the cells. In addition to the optimization of a magnetic bead-based benchtop protocol for generating and transforming electrocompetent E. coli cells, we report on the implementation of this protocol in a fully automated digital microfluidic platform. Bead-based media exchange and electroporation pulse conditions were optimized on benchtop for transformation frequency to provide initial parameters for microfluidic device trials. Benchtop experiments comparing electrotransformation of free and bead-bound cells are presented. Our results suggest that dielectric shielding intrinsic to bead-bound cells significantly reduces electroporation field exposure efficiency. However, high transformation frequency can be maintained in the presence of magnetic beads through the application of more intense electroporation pulses. As a proof of concept, MAGE cycles were successfully performed on a commercial EWoD cartridge using variations of the optimal magnetic bead-based preparation procedure and pulse conditions determined by the benchtop results. Transformation frequencies up to 22% were achieved on benchtop; this frequency was matched within 1% (21%) by MAGE cycles on the microfluidic device. However, typical frequencies on the device remain lower, averaging 9% with a standard deviation of 9%. The presented results demonstrate the potential of digital microfluidics to perform complex and automated genetic engineering protocols.


Equivalent effective doses of heparin and low molecular weight heparin(oid)s in haemodialysis for chronic renal failure.
In an attempt to provide an objective means of comparing the anticoagulant action of heparin with those of newly developed low MW heparin-like anticoagulants we have utilized the fibrinpeptide A assay as a method of determining fibrin formation during haemodialysis. In vivo suppression of FPA levels by increasing doses of administered anticoagulant enables equivalent effective doses of anticoagulants to be determined without making prior assumptions about which ex vivo activities of these compounds are responsible. In this communication we summarize results of studies with heparin and three low MW heparin(oid)s.


Psychometric prediction of penitentiary recidivism.
Attempts to predict prison recidivism based on the personality have not been very successful. This study aims to provide data on recidivism prediction based on the scores on a personality questionnaire. For this purpose, a predictive model combining the actuarial procedure with a posteriori probability was developed, consisting of the probabilistic calculation of the effective verification of the event once it has already occurred. Cuestionario de Personalidad Situacional (CPS; Fernández, Seisdedos, & Mielgo, 1998) was applied to 978 male inmates classified as recidivists or non-recidivists. High predictive power was achieved, with the area under the curve (AUC) of 0.85 (p <.001; Se = 0.012; 95% CI [0.826, 0.873]. The answers to the CPS items made it possible to properly discriminate 77.3% of the participants. These data indicate the important role of the personality as a key factor in understanding delinquency and predicting recidivism.


Sedentary Behavior and Sleep Problems: a Systematic Review and Meta-Analysis.
Sedentary behavior, characterized by a sitting or reclining posture and low-energy expenditure, has been recognized as an independent health risk factor. We conducted a systematic review and meta-analysis to examine the association between sedentary behavior and sleep problems. Keyword and reference search were performed in PubMed, Cochrance Library, and Web of Science databases to identify relevant studies. The methodological quality of each study was assessed by standardized tools. The pooled estimates on the relationship between sedentary behavior and sleep problems were calculated in meta-analysis. Subgroup analyses were conducted for studies examining alternative sedentary behavior types, using self-reported or objective measures of sedentary behavior, different age groups, and assessed with different study quality levels. Sixteen eligible studies were identified through a literature search. Meta-analysis found sedentary behavior to be associated with an increased risk of insomnia (pooled odds ratio [POR] = 1.176, 95% confidence interval [CI] = 1.014-1.364) and sleep disturbance (POR = 1.381, 95% CI = 1.282-1.488). No association between sedentary behavior and daytime sleepiness and/or poor sleep quality was observed. Except for study quality levels, no significant differences in sleep disturbance were observed across alternative sedentary behavior types, sedentary behavior measures, and age groups in subgroup analyses. Prolonged sedentary behavior tends to be associated with an elevated risk of insomnia and sleep disturbance in the existing literature. Future studies with experimental study design and longer follow-up periods are warranted to demonstrate the long-term causal impact of sedentary behavior on sleep problems.


Psychometric evidence of self-reported questionnaires for patellofemoral pain syndrome: a systematic review.
To conduct a systematic review of psychometric properties of self-reported questionnaires used to assess the level of symptoms and disability in individuals with patellofemoral pain syndrome (PFPS). A structured search was conducted in four databases (Medline, Embase, CINAHL, SportDiscus). A total of 24 studies about five different self-reported questionnaires were analyzed. A pair of independent raters extracted data on validity, reliability and responsiveness to change, and performed critical appraisal (0-100%). Activities of Daily Living Scale (ADLS), Anterior Knee Pain Scale (AKPS), International Knee Documentation Committee (IKDC) and Lysholm Scale (LS) present excellent test-retest reliability (weighted average intraclass correlation coefficients [ICC] > 0.80), whereas Functional Index Questionnaire (FIQ) is moderately reliable (ICC = 0.61). Minimal detectable change is 8.3% for ADLS, 9.0% for AKPS, 19% for FIQ, 8.5% for IKDC and 30% for LS. ADLS, AKPS, IKDC and LS are highly responsive (effect size/standardized response mean >0.95) in individuals with PFPS, while FIQ is lowly responsive (effect size = 0.49). Based on available evidence, ADLS presents the best psychometric properties and should be preferred when evaluating patients with PFPS. AKPS and IKDC are also adequate, while FIQ and LS are not recommended for individuals with PFPS. While several questionnaires have been developed to assess symptoms and functional limitations caused by knee pain, their psychometric properties can vary depending on the condition presented by the patient. The Activities of Daily Living Scale of the Knee Outcome Survey should be preferred by clinicians when evaluating a patient with PFPS. The Anterior Knee Pain Scale and International Knee Documentation Committee Subjective knee evaluation are also adequate for use with this population. The Functional Index Questionnaire and Lysholm Scale are not recommended for PFPS.


EEG changes and platelet aggregation in experimental cerebral focal ischemia in rabbits.
Nine white New Zealand rabbits were submitted to internal carotid embolization with microspheres which caused a histologically verified focal cerebral ischemia. Six animals were sham-operated. EEG, QEEG, ECG, blood pressure, rectal temperature and platelet aggregation were monitored in basal conditions and one hour after ischemia. Embolized animals showed an increase in power density spectrum (PDS) and delta activity (0.15-3.70 Hz) and the appearance of platelet aggregation. The QEEG changes were correlated to the degree of platelet aggregation after ischemia.


Types of diabetes are not limited to age groups: type 1 diabetes in adults and type 2 diabetes in children and adolescents.
Based on data from the national diabetes registry DPV (Diabetes patient documentation), the diabetes registry of North Rhine-Westphalia and surveys conducted at hospitals and practices in Baden-Württemberg and Saxony, this study estimates the incidence and prevalence of type 1 diabetes in over-18-year-old adults and type 2 diabetes in 11- to 18-year-old children and adolescents. The national incidence of type 1 diabetes in adults was 6.1 per 100,000 person-years from 2014 to 2016, with slightly lower figures for women compared to men. Annually, around 4,150 adults develop type 1 diabetes. In 2016, the prevalence of type 1 diabetes was estimated at 493 per 100,000 persons and was lower in women at 445 per 100,000 people than in men at 544 per 100,000. Based on this data, there were around 341,000 adults with type 1 diabetes in 2016. For 11- to 18-year-old children and adolescents, the national incidence of type 2 diabetes was 2.8 per 100,000 person-years between 2014 and 2016 and higher for girls than for boys. Annually, around 175 adolescents in this age group develop type 2 diabetes. The incidence estimates for Saxony were higher (4.3 per 100,000 person-years). The prevalence of type 2 diabetes between 2014 and 2016 for 11- to 18-year-old children and adolescents was estimated between 12 and 18 cases per 100,000 persons. During this period, there were about 950 children and adolescents of this age group with type 2 diabetes in Germany.


Asymmetry assessment using cone beam CT. A Class I and Class II patient comparison.
To estimate possible differences in skeletal asymmetry between patients with skeletal Class I and skeletal Class II relationships. Cone beam computed tomography (CBCT) images were examined from 70 consecutive patients who presented for orthodontic care and fit the inclusion criteria. Asymmetry was quantified using an asymmetry index developed by Katsumata et al. Anatomic landmarks were defined and reference planes were established to determine the asymmetry of the landmarks using a constructed coordinate plane system. Thirty randomly selected patients were reanalyzed to assess the reliability of the method. Statistical analysis did not find any significant relationship between asymmetry and A-P skeletal relationship for any of the landmarks. Asymmetry index scores were reproducible within a certain range of agreement for each landmark. Based on this study, the discrepant jaw growth resulting in a Class II skeletal pattern results in no more skeletal asymmetry than Class I skeletal patterns.


Serum 25-hydroxyvitamin D3 is related to physical activity and ethnicity but not obesity in a multicultural workforce.
Recent research suggests that body vitamin D levels are decreased in coronary heart disease and diabetes, but it is unclear which cardiovascular risk factors are related to vitamin D status. To examine the relation between vitamin D status and major cardiovascular risk factors. Serum 25-hydroxyvitamin D3, a marker of recent sun exposure and vitamin D status, was measured in 390 New Zealand residents (95 Pacific Islanders, 74 Maori and 221 others mostly of European descent), who were part of a larger cross-sectional survey of a workforce (n = 5677) aged 40-64 years. Serum 25-hydroxyvitamin D3 levels were significantly lower in Pacific Islanders (mean (SE) = 56 (3) nmol/L; p = 0.0001) and Maoris (68 (3) nmol/L; p = 0.036) compared with Europeans (75 (2) nmol/L) after adjusting for age, sex and time of year. Also adjusting for ethnic group, 25-hydroxyvitamin D3 was higher in people doing vigorous (aerobic) leisure physical activities (71 (2) nmol/L; p = 0.0066) and moderate (non-aerobic) activities (68 (3) nmol/L; p = 0.12) compared with those who were inactive (63 (2) nmol/L). However, 25-hydroxyvitamin D3 was unrelated to body mass index, serum lipids, blood pressure or cigarette smoking. People with increased skin pigmentation, such as Polynesians, and people who are inactive, have decreased body levels of vitamin D; this might partly explain their increased risk of cardiovascular disease.


The parvocellular vasotocin system of Japanese quail: a developmental and adult model for the study of influences of gonadal hormones on sexually differentiated and behaviorally relevant neural circuits.
Vasotocin (VT; the antidiuretic hormone of birds) is synthesized by diencephalic magnocellular neurons projecting to the neurohypophysis. A sexually dimorphic system of VT-immunoreactive (ir) parvocellular elements has been described within the male medial preoptic nucleus (POM) and the nucleus of the stria terminalis, pars medialis (BSTm). VT-ir fibers are present in many diencephalic and extradiencephalic locations, and quantitative morphometric analyses demonstrated their sexually dimorphic distribution in regions involved in the control of different aspects of reproduction. Moreover, systemic or intracerebroventricular injections of VT markedly inhibit the expression of some aspects of male sexual behavior. In adult animals, circulating levels of testosterone (T) have a profound influence on the VT immunoreactivity within BSTm, POM, and lateral septum. Castration markedly decreases the immunoreaction, whereas T-replacement therapy restores a situation similar to the intact birds. We observed no changes in gonadectomized females treated with T. These changes parallel similar changes in male copulatory behavior (not present in castrated male quail, fully expressed in castrated, T-treated males). The restoration by T of the VT immunoreactivity in castrated male quail could be fully mimicked by a treatment with estradiol (E(2)), suggesting that the aromatization of T into E(2) may play a key limiting role in both the activation of male sexual behavior and the induction of VT synthesis. This dimorphism has an organizational nature: administration of E(2) to quail embryos (a treatment that abolishes male sexual behavior) results in a dramatic decrease of the VT immunoreactivity in sexually dimorphic regions. Conversely, the inhibition of E(2) synthesis during embryonic life (a treatment that stimulates the expression of male copulatory behavior in treated females exposed in adulthood to T) results in a malelike distribution of VT immunoreactivity. The VT parvocellular system of the Japanese quail can therefore be considered an accurate marker of the sexual differentiation of brain circuits mediating copulatory behavior and could be a very sensitive indicator of the activity of estrogenlike substances on neural circuits.


Rapid identification of soil cadmium pollution risk at regional scale based on visible and near-infrared spectroscopy.
Soil heavy metal pollution due to long-term sewage irrigation is a serious environmental problem in many irrigation areas in northern China. Quickly identifying its pollution status is an important basis for remediation. Visible-near-infrared reflectance spectroscopy (VNIRS) provides a useful tool. In a case study, 76 soil samples were collected and their reflectance spectra were used to estimate cadmium (Cd) concentration by partial least squares regression (PLSR) and back propagation neural network (BPNN). To reduce noise, six pre-treatments were compared, in which orthogonal signal correction (OSC) was first used in soil Cd estimation. Spectral analysis and geostatistics were combined to identify Cd pollution hotspots. Results showed that Cd was accumulated in topsoil at the study area. OSC can effectively remove irrelevant information to improve prediction accuracy. More accurate estimation was achieved by applying a BPNN. Soil Cd pollution hotspots could be identified by interpolating the predicted values obtained from spectral estimates.


CA-125 level is associated with right ventricular echocardiographic parameters in patients with COPD.
A few studies have shown that elevated CA-125 levels are associated with chronic obstructive pulmonary disease (COPD). However, there are no data concerning the associaton between serum CA-125 levels and right ventricular (RV) function in COPD patients. This study aimed to evaluate the relationship between CA-125 level and RV echocardiographic parameters in COPD patients. Fifty-two patients with COPD (39 male/13 female, mean age 68.9 ± 5.7 years) were studied. The control group consisted of 30 age-sex matched healthy volunteers (23 male/7 female, mean age 64.2 ± 6.3 years). Patients were divided into two subgroups: patients without pulmonary hypertension (group I, n = 25) and with pulmonary hypertension (group II, n = 27). Conventional echocardiographic parameters, tissue Doppler imaging (TDI) and CA-125 level measurements were performed in all subjects. Patients in group II had significantly higher CA-125 levels than those in group I and controls (P < 0.01). CA-125 levels in group I were also higher than control group (P < 0.05). CA-125 levels were correlated with left ventricle E/A ratio, systolic pulmonary artery pressure (sPAP), RV myocardial performance index, and RV fractional area change (r = 0.37, 0.56, 0.34, and -0.42, respectively, all with P < 0.05). There was an independent correlation between CA-125 levels and sPAP values (β = 0.76, P < 0.001). Our results show an independent correlation between CA-125 levels and systolic pulmonary artery pressure in COPD patients. The clinical utility of these results at this point in time is unknown and deserves future research.


[Congenital heart defects in the county of Fyn. Epidemiology and mortality 1986-1995].
The aim was to describe the prevalence of congenital heart diseases (CHD), mortality during the first year of life, and the impact of associated malformations on survival. All children born in the County of Fyn in 1986-1995, who were diagnosed with CHD and recorded in the Eurocat Registry of Congenital Malformation were entered. The registry is population-based and the information is derived from multiple sources. It covers live births, fetal deaths with a GA (gestational age) > or = 20 weeks, and induced abortions after prenatal diagnosis of congenital malformations. Only cases diagnosed by echocardiography, catheterisation, surgery, or post mortem examination were included. Four hundred and forty-six infants born during the study period were diagnosed with CHD before 1998, giving a prevalence of 8.0 per 1,000 live births. The prevalence of ASD + VSD had increased in the period of 1991-1995 compared to 1986-1990 although not significantly. Ten per cent had karyotype anomalies and nine per cent had associated malformations. Only 3% were diagnosed prenatally, 49% were diagnosed before the age of one week, and ten per cent were diagnosed after the first year of life. CHD mortality during the first year of life was 18% (80/446) and was significantly increased for infants with associated malformations (p < 0.01) or karyotype anomalies other than Down syndrome (p < 0.01). The prevalence of CHD in the County of Fyn corresponds to the data in the literature. At the time of introduction of colour Doppler echocardiography there was an increase in the proportion of infants diagnosed with ASD and VSD, although not significantly. Mortality was high, but 20% of deaths were infants with a hypoplastic left heart. In regions with prenatal ultrasound screening for malformations, this was often diagnosed prenatally followed by termination of pregnancy. For infants with CHD, it is important to verify, whether there are associated malformations or karyotype anomalies, as they have a significant impact on the prognosis.


Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation.
The amyloid-beta precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated amyloid-beta (A beta) peptide formation. The predominant site of caspase-mediated proteolysis is within the cytoplasmic tail of APP, and cleavage at this site occurs in hippocampal neurons in vivo following acute excitotoxic or ischemic brain injury. Caspase-3 is the predominant caspase involved in APP cleavage, consistent with its marked elevation in dying neurons of Alzheimer's disease brains and colocalization of its APP cleavage product with A beta in senile plaques. Caspases thus appear to play a dual role in proteolytic processing of APP and the resulting propensity for A beta peptide formation, as well as in the ultimate apoptotic death of neurons in Alzheimer's disease.