The RTK Interactome: Overview and Perspective on RTK Heterointeractions.
Receptor tyrosine kinases (RTKs) play important roles in cell growth, motility, differentiation, and survival. These single-pass membrane proteins are grouped into subfamilies based on the similarity of their extracellular domains. They are generally thought to be activated by ligand binding, which promotes homodimerization and then autophosphorylation in trans. However, RTK interactions are more complicated, as RTKs can interact in the absence of ligand and heterodimerize within and across subfamilies. Here, we review the known cross-subfamily RTK heterointeractions and their possible biological implications, as well as the methodologies which have been used to study them. Moreover, we demonstrate how thermodynamic models can be used to study RTKs and to explain many of the complicated biological effects which have been described in the literature. Finally, we discuss the concept of the RTK interactome: a putative, extensive network of interactions between the RTKs. This RTK interactome can produce unique signaling outputs; can amplify, inhibit, and modify signaling; and can allow for signaling backups. The existence of the RTK interactome could provide an explanation for the irreproducibility of experimental data from different studies and for the failure of some RTK inhibitors to produce the desired therapeutic effects. We argue that a deeper knowledge of RTK interactome thermodynamics can lead to a better understanding of fundamental RTK signaling processes in health and disease. We further argue that there is a need for quantitative, thermodynamic studies that probe the strengths of the interactions between RTKs and their ligands and between different RTKs.


Glucose concentration at possible sensor tissue implant sites.
It is generally acknowledged that the ideal automatic insulin infusion system would be a closed loop that metered insulin delivery in response to a feedback sensor such as an implantable glucose detector. Most current efforts are aimed at a transducer located within the blood vascular tree. We believe that the blood constitutes an especially hostile environment for such a device. The possibility of placing the sensor with a reasonably rapid response to dynamic alterations in glucose metabolism in a space containing fluid outside the bloodstream was studied. The subcutaneous extracellular space, peritoneum, pleura, and pericardium were included. Generally, the concentration of glucose ranged between 50 and 115 mg/dl under steady-state conditions. The experimental design did not permit monitoring rapid responses to artificially induced dynamic changes. There were several situations where lower values were recorded, suggesting that a wide range of concentrations might occur. The authors have concluded that these experimental results are compatible with the possibility of a suitable locus for the glucose sensor in the extracellular, extravascular space.


Engagement in family activities: a quantitative, comparative study of children with profound intellectual and multiple disabilities and children with typical development.
Participation is known to be of great importance for children's development and emotional well-being as well as for their families. In the International Classification of Functioning, Disability and Health - Children and Youth version participation is defined as a person's 'involvement in a life situation'. Engagement is closely related to involvement and can be seen as expressions of involvement or degree of involvement within a situation. This study focuses on children's engagement in family activities; one group of families with a child with profound intellectual and multiple disabilities (PIMD) and one group of families with children with typical development (TD) were compared. A descriptive study using questionnaires. Analyses were mainly performed by using Mann-Whitney U-test and Spearman's rank correlation test. Engagement in family activities differed in the two groups of children. The children with PIMD had a lower level of engagement in most family activities even though the activities that engaged the children to a higher or lesser extent were the same in both groups. Child engagement was found to correlate with family characteristics mostly in the children with TD and in the children with PIMD only negative correlations occurred. In the children with PIMD child engagement correlated with cognition in a high number of listed family activities and the children had a low engagement in routines in spite of these being frequently occurring activities. Level of engagement in family activities in the group of children with PIMD was lower compared with that in the group of children with TD. Families with a child with PIMD spend much time and effort to adapt family living patterns to the child's functioning.


Deoxynivalenol (DON)-Triggered Dual-Color Composite Probe Based on Gold Nanoclusters for Simultaneous Imaging of DON and miR-34a in Living Cells.
Deoxynivalenol (DON) is a mycotoxin secreted by Fusarium species, posing great harm to food safety and human health. Therefore, it is of great significance to study its toxic effects and mechanism. miR-34a is a representative biomarker during the process of DON-induced apoptosis. Herein, a DON-triggered dual-color composite probe was constructed for simultaneous imaging of DON and miR-34a in living cells. The aptamer blocks the recognition sequence of miR-34a to realize DON-triggered cell imaging. The specific binding of DON with its aptamer and HCR induced by miR-34a resulted in the recovery of fluorescence of the dual-color Au NCs. Under the optimal conditions, the correlation between the relative fluorescence intensities of dual-color Au NCs showed good linear relationships with the logarithm of DON and miR-34a concentration, respectively. With the increase in DON concentration (0-20 μg/mL) and stimulation time (0-12 h), the fluorescence of dual-color Au NCs gradually recovered. This dual-color Au NCs composite probe can realize simultaneous detection of DON and miR-34a induced by DON, which is significant for verifying the cytotoxic mechanism of DON.


MicroRNA-155 is required for clearance of Streptococcus pneumoniae from the nasopharynx.
Pneumonia caused by Streptococcus pneumoniae is a major cause of death and an economic burden worldwide. S. pneumoniae is an intermittent colonizer of the human upper respiratory tract, and the ability to control asymptomatic colonization determines the likelihood of developing invasive disease. Recognition of S. pneumoniae by resident macrophages via Toll-like receptor 2 (TLR-2) and the macrophage receptor with collagenous structure (MARCO) and the presence of interleukin-17 (IL-17)-secreting CD4(+) T cells are required for macrophage recruitment and bacterial clearance. Despite the fact that the primary cellular effectors needed for bacterial clearance have been identified, much of the underlying regulatory mechanisms are unknown. Herein, we demonstrate that the small, noncoding RNA microRNA-155 (mir-155) is critical for the effective clearance of S. pneumoniae. Our studies show that mir-155-deficient mice maintain the ability to prevent acute invasive pneumococcal infection but have significantly higher bacterial burdens following colonization, independently of macrophage recognition by TLR-2, MARCO expression, or bactericidal capacity. The observed defects in bacterial clearance parallel reduced IL-17A and gamma interferon CD4(+) T-cell responses in vivo, lower IL-17A mRNA levels in the nasopharynx, and a reduced capacity to induce Th17 cell polarization. Given that knockout mice are also limited in the capacity to generate high-titer S. pneumoniae-specific antibodies, we conclude that mir-155 is a critical mediator of the cellular effectors needed to clear primary and secondary S. pneumoniae colonizations.


Where there is sodium there may be sepsis.
Hypernatremia affects up to 9% of critically ill patients upon hospital admission, especially in elderly patients with thirst impairment. However, hypernatremia is not entirely explained by fluid imbalance. Recent studies suggest that sodium is an important enhancer of the immune system, raising the question of whether inflammatory states such as sepsis may contribute to hypernatremia. Although sepsis patients with hypernatremia face a greater mortality rate, there is a lack of studies examining a potential association between hypernatremia and sepsis. Motivated by the frequent concurrence of hypernatremia and sepsis observed at an eastern Pennsylvanian community hospital, the current study was conducted to evaluate whether hypernatremia on admission may serve as a potential surrogate marker for sepsis. The medical records of 153 patients with hypernatremia on admission (serum sodium > 145mEq/L) were retrospectively analyzed. The mean age of patients was 81.1. Sepsis was observed in 77.1% of patients, of which 86.2% had dementia. This study demonstrated a positive correlation between hypernatremia on admission and the presence of sepsis. We suggest that the existence of hypernatremia should prompt clinicians to further investigate for sources of infection, especially in the elderly and patients with dementia.


[Ocular tuberculosis in systemic lupus erythematosus and immunosuppressive therapy].
A marked reduction in eye disease attributed to tuberculosis has occurred over the past several decades. In recent years, however, tuberculosis has reemerged as a serious public health problem. We report a case of a severe ocular tuberculosis in a patient with systemic lupus erythematosus and immunosuppressive therapy. The 36-years-old woman underwent an immunosuppressive therapy because of a systemic lupus erythematosus detected two years earlier. After holidays on the Philippines Mycobacterium tuberculosis was found in a bronchial lavage. Two months later fundoscopy showed severe subretinal exsudation with overlying serous retinal detachment. Within several months these findings progressed to a panuveitis with spontaneous perforation. Histopathologically a granulomatous panophthalmitis could be found with giant cells. Two months later acid-fast bacilli were detected in orbital lesions. In immunosuppressed patients there is still an increased risk for severe ocular tuberculosis. Therefore it is important to think of this almost forgotten disease in those cases.


Antibodies to bovine liver branched-chain 2-oxo acid dehydrogenase cross-react with this enzyme complex from other tissues and species.
Antibodies were produced in rabbits against bovine liver branched-chain 2-oxo acid dehydrogenase (BCOAD) for three reasons. First, since activity of BCOAD varies among tissues within a species, it is necessary to ascertain whether isoenzymes exist within the different tissues. Second, it is of great interest to determine the structural similarity of BCOAD among mammalian species. Third, heritable defects of this multienzyme complex are known in humans, and techniques for studying BCOAD subunit composition in cells expressing the defect include the use of specific antibodies. Antibodies produced against BCOAD inhibit complex activity and cross-react with BCOAD from various tissues and species. By using rocket immunoelectrophoresis, the complex can be quantified in mitochondrial extracts. Each subunit is immunogenic, making the detection of subunit variants possible by the combined techniques of sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and Western blotting. Finally, antibodies produced against pig heart lipoamide dehydrogenase cross-react with BCOAD, pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes, giving further evidence for the commonality of this subunit among these three mitochondrial complexes.


The first multi-gene phylogeny of the Macrostomorpha sheds light on the evolution of sexual and asexual reproduction in basal Platyhelminthes.
The Macrostomorpha-an early branching and species-rich clade of free-living flatworms-is attracting interest because it contains Macrostomum lignano, a versatile model organism increasingly used in evolutionary, developmental, and molecular biology. We elucidate the macrostomorphan molecular phylogeny inferred from both nuclear (18S and 28S rDNA) and mitochondrial (16S rDNA and COI) marker genes from 40 representatives. Although our phylogeny does not recover the Macrostomorpha as a statistically supported monophyletic grouping, it (i) confirms many taxa previously proposed based on morphological evidence, (ii) permits the first placement of many families and genera, and (iii) reveals a number of unexpected placements. Specifically, Myozona and Bradynectes are outside the three classic families (Macrostomidae, Microstomidae and Dolichomacrostomidae) and the asexually fissioning Myomacrostomum belongs to a new subfamily, the Myozonariinae nov. subfam. (Dolichomacrostomidae), rather than diverging early. While this represents the first evidence for asexuality among the Dolichomacrostomidae, we show that fissioning also occurs in another Myozonariinae, Myozonaria fissipara nov. sp. Together with the placement of the (also fissioning) Microstomidae, namely as the sister taxon of Dolichomacrostomidae, this suggests that fissioning is not basal within the Macrostomorpha, but rather restricted to the new taxon Dolichomicrostomida (Dolichomacrostomidae+Microstomidae). Furthermore, our phylogeny allows new insights into the evolution of the reproductive system, as ancestral state reconstructions reveal convergent evolution of gonads, and male and female genitalia. Finally, the convergent evolution of sperm storage organs in the female genitalia appears to be linked to the widespread occurrence of hypodermic insemination among the Macrostomorpha.


Comparison of Nanohole-Type and Nanopillar-Type Patterned Metallic Electrodes Incorporated in Organic Solar Cells.
Both the nanohole- and nanopillar-type patterned metallic electrodes (PMEs) have been introduced in organic solar cells (OSCs) for improving device performances experimentally, but there is few work addressing the similarities and differences between them. In this theoretical work, we systematically compare the impact of the nanohole- and nanopillar-type PMEs on the performance of an OSC based on hybridized cavity resonances. By optimizing the geometrical parameters of each PME, we obtained an interesting result that the integrated absorption efficiencies in the active layer with different optimized PMEs are almost the same (both are equal to 82.4%), outperforming that of the planar control by 9.9%. Though the absorption enhancement spectra of the two different optimal devices are similar as well, the mechanisms of light trapping at the corresponding enhancement peaks are distinct from each other. In a comprehensive view, the nanopillar-type PME is suggested to be applied in the present system, since its optimal design has a moderate filling ratio, which is much easier to fabricate than its counterpart. This work could contribute to the development of high-efficiency OSCs.


Clinical Features of Late-onset Semantic Dementia.
Semantic dementia (SD) is characterized by progressive semantic anomia extending to a multimodal loss of semantic knowledge. Although often considered an early-onset dementia, SD also occurs in later life, when it may be misdiagnosed as Alzheimer disease (AD). To evaluate late-onset SD in comparison to early-onset SD and to AD. We identified 74 individuals with SD and then compared those with late-onset SD (≥65 years of age) to those with early-onset SD (<65) on demographic and clinical features. We also compared a subgroup of 23 of the late-onset SD individuals with an equal number of individuals with clinically probable AD. Twenty-six (35.1%) of the SD individuals were late onset, and 48 (64.9%) were early onset. There were no differences between the two groups on clinical measures, although greater asymmetry of temporal involvement trended to significance in the late-onset SD group. Compared to the 23 AD individuals, the subgroup of 23 late-onset SD individuals had worse performance on confrontational naming, irregular word reading, and face recognition; however, this subgroup displayed better verbal delayed recall and constructions. The late-onset SD individuals also experienced early personality changes at a time when most individuals with AD had not yet developed behavioral changes. Approximately one-third of SD individuals may be late onset, and the differentiation of late-onset SD from AD can lead to better disease management, education, and prognosis. SD may be distinguished by screening for disproportionate changes in reading, face recognition, and personality.


Femtosecond laser-assisted deep anterior lamellar keratoplasty.
A survey of the recent literature of deep anterior lamellar keratoplasty using femtosecond laser technology. There are several recent reports in the literature assessing technique and outcomes of deep anterior lamellar keratoplasty done with a femtosecond laser trephination. Most of these reports are laboratory studies and small case series with short-term outcomes. The laser technology is expensive and may not produce better results than conventional manual techniques. However, there are several theoretical advantages to femtosecond laser incisions in deep anterior lamellar keratoplasty that should be explored, including possible increased success of Descemet's membrane separation from stroma during surgery as well as postsurgical astigmatism benefits, earlier suture removal, and increased wound strength and healing. Femtosecond laser trephination in the setting of DALK may improve the technique by decreasing the number of descemet's membrane ruptures and improving short-term and long-term outcomes as compared with manual techniques. However, there is no consensus on a standardized approach for wound design or postoperative management. The literature would benefit from a prospective randomized controlled trial.


Adverse skin reactions during treatment with cetuximab plus radiotherapy: Multidisciplinary approach to minimize radio-chemotherapy interruption.
Antibodies against the epidermal growth factor receptor (EGFR), such as cetuximab, are effective in loco-regional advanced squamous cell carcinoma of the head and neck (SCCHN) in association with radiotherapy. Cutaneous reactions are well known as adverse events during treatment with EGFR inhibitors. To identify a multidisciplinary approach for mucous-cutaneous toxicity during cetuximab-radiotherapy treatment in order to reduce the risk of an early radio-chemotherapy interruption. The data of 38 patients with SCCHN receiving cetuximab and radiotherapy were retrospectively analyzed. The control group (n = 15) received the standardized treatments according to the severity of skin reactions with dermatologic visits only for high degrees of toxicity. The experimental group (n = 23) was monitored and daily treated by dermatologists since grade 1 of cutaneous toxicity. The primary end-point of our study was the mean days of antitumor therapy interruption. The mean number of days of antitumor therapy suspension was 12.6 (7.6) in the standard treatment group and 5.0 (6.6) in the experimental group (p = 0.002). This difference was observed for each grade of toxicity. The early interruption of radio-chemotherapy has a negative impact on survival in patients with SCCHN. In our study, a closer dermatological examination and treatment for all degrees of toxicity reduced early interruptions of chemo-radiotherapy.


The maze and the minotaur: mental health in primary health care.
The article aims to discuss the issue of integration of mental health in primary care by matrix support in mental health. We point out the main barriers in the use of this work method, as well as the facilitating factors of the matrix support of mental health in primary care. The first are within the scope of epistemological specificities, professional issues and management in the political and ideological dimensions. Among the second, we highlight: the care for people with mental disorders in the territory; the reduction of stigma and discrimination; the development of new skills for professionals in primary care; reduction of costs; simultaneous treatment of physical and mental illness, which often overlap; the possibility of incorporating mental health care in a perspective of extended clinical service using an inter/transdisciplinary approach.


Evaluating the return in ecosystem services from investment in public land acquisitions.
We evaluate the return on investment (ROI) from public land conservation in the state of Minnesota, USA. We use a spatially-explicit modeling tool, the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST), to estimate how changes in land use and land cover (LULC), including public land acquisitions for conservation, influence the joint provision and value of multiple ecosystem services. We calculate the ROI of a public conservation acquisition as the ratio of the present value of ecosystem services generated by the conservation to the cost of the conservation. For the land scenarios analyzed, carbon sequestration services generated the greatest benefits followed by water quality improvements and recreation opportunities. We found ROI values ranged from 0.21 to 5.28 depending on assumptions about future land use change, service values, and discount rate. Our study suggests conservation is a good investment as long as investments are targeted to areas with low land costs and high service values.


Crestal Sinus Floor Augmentation Using Hydraulic Pressure and Vibrations: A Retrospective Single Cohort Study.
To evaluate the sinus membrane perforation and implant survival rate after crestal minimally invasive sinus floor augmentation using hydraulic pressure and vibrations. In this retrospective single cohort study, all patients who underwent minimally invasive sinus floor augmentation between 2007 and 2015 using hydraulic pressure and vibrations were included. The sinus membrane is elevated by physiologic saline at 1.5 bar. The fluid is then set into vibration to further separate the sinus membrane from the bony floor. The endpoints were sinus membrane perforation and the survival rate of implants. The hydraulic pressure and vibration technique was applied in 156 patients. Seven patients with perforations of the sinus membrane were treated with the lateral window approach and excluded from the follow-up analysis. In the remaining 149 patients, 184 crestal sinus floor augmentations were performed and 184 implants were placed. In 10 of these 184 cases, a perforation was suspected in the postoperative computed tomography (CT) scan. In total, the perforation rate was 8.9% (17/191). Nineteen implants were lost during the follow-up period ranging from 0.2 to 8.4 years with a median of 2.3 years. The cumulative implant survival rates after 1, 3, and 5 years were 94.4%, 87.7%, and 87.7%, respectively. No severe perioperative complications were noted. The hydraulic pressure and vibration technique allows a minimally invasive crestal sinus augmentation with a perforation rate less than 10% and implant survival rates of approximately 90%.


A path recorder algorithm for Multiple Longest Common Subsequences (MLCS) problems.
Searching the Longest Common Subsequences of many sequences is called a Multiple Longest Common Subsequence (MLCS) problem which is a very fundamental and challenging problem in many fields of data mining. The existing algorithms cannot be applicable to problems with long and large-scale sequences due to their huge time and space consumption. To efficiently handle large-scale MLCS problems, a Path Recorder Directed Acyclic Graph (PRDAG) model and a novel Path Recorder Algorithm (PRA) are proposed. In PRDAG, we transform the MLCS problem into searching the longest path from the Directed Acyclic Graph (DAG), where each longest path in DAG corresponds to an MLCS. To tackle the problem efficiently, we eliminate all redundant and repeated nodes during the construction of DAG, and for each node, we only maintain the longest paths from the source node to it but ignore all non-longest paths. As a result, the size of the DAG becomes very small, and the memory space and search time will be greatly saved. Empirical experiments have been performed on a standard benchmark set of both DNA sequences and protein sequences. The experimental results demonstrate that our model and algorithm outperform the related leading algorithms, especially for large-scale MLCS problems. This program code is written by the first author and can be available at https://www.ncbi.nlm.nih.gov/nuccore and https://blog.csdn.net/wswguilin. Supplementary data are available at Bioinformatics online.


Bartonellae of Synanthropic Four-Striped Mice (Rhabdomys pumilio) from the Western Cape Province, South Africa.
Bartonella is a species-rich bacterial genus that infects a wide variety of wild and domestic animals, including rodents. Despite high levels of murid rodent diversity in Africa, associated Bartonella prevalence and diversity remains understudied, particularly within the southern African subregion. To address this, we sampled endemic four-striped mice, Rhabdomys pumilio, from three rural and two urban localities in the Western Cape Province, South Africa. PCR screening and multilocus sequence analysis inclusive of five genome regions (gltA, nuoG, ribC, rpoB, and ITS), were respectively used to evaluate Bartonella status and diversity in these synanthropic rodent populations. An overall infection rate of 15% was recovered, ranging from 0% for an urban locality to 36.4% for a rural locality, consistent with the higher flea abundance recorded at the latter sites. Nucleotide sequencing and phylogenetic analyses confirmed the presence of three distinct Bartonella lineages (I-III), with lineages II and III grouping with bartonellae previously detected in R. pumilio from nature reserves in the Free State Province of South Africa, and lineage I being novel and sister to Bartonella strains identified previously in Micaelamys namaquensis. Our results indicate significant landscape effects on infection rates, highlight differential PCR assay performance, and identify three host-associated Bartonella lineages in Rhabdomys from South Africa.


[Cholesterol esterase activity of human monocytes in ischemic heart disease].
The comparison on the effect of atherosclerotic lesion of the vascular system on changes in the activity of human blood mononuclear cell lysosomal and cytoplasmic cholesterolesterases showed that these changes were of diverse nature an increase in lysosomal cholesterolesterase activity and a decrease in cytoplasmatic activity. It can be accounted for be a different role of acid and alkaline cholesteroesterases in cell cholesterol metabolism and by different mechanisms of the regulation of these enzymes.


Post-mortem molecular profiling of three psychiatric disorders.
Psychiatric disorders are multigenic diseases with complex etiology that contribute significantly to human morbidity and mortality. Although clinically distinct, several disorders share many symptoms, suggesting common underlying molecular changes exist that may implicate important regulators of pathogenesis and provide new therapeutic targets. We performed RNA sequencing on tissue from the anterior cingulate cortex, dorsolateral prefrontal cortex, and nucleus accumbens from three groups of 24 patients each diagnosed with schizophrenia, bipolar disorder, or major depressive disorder, and from 24 control subjects. We identified differentially expressed genes and validated the results in an independent cohort. Anterior cingulate cortex samples were also subjected to metabolomic analysis. ChIP-seq data were used to characterize binding of the transcription factor EGR1. We compared molecular signatures across the three brain regions and disorders in the transcriptomes of post-mortem human brain samples. The most significant disease-related differences were in the anterior cingulate cortex of schizophrenia samples compared to controls. Transcriptional changes were assessed in an independent cohort, revealing the transcription factor EGR1 as significantly down-regulated in both cohorts and as a potential regulator of broader transcription changes observed in schizophrenia patients. Additionally, broad down-regulation of genes specific to neurons and concordant up-regulation of genes specific to astrocytes was observed in schizophrenia and bipolar disorder patients relative to controls. Metabolomic profiling identified disruption of GABA levels in schizophrenia patients. We provide a comprehensive post-mortem transcriptome profile of three psychiatric disorders across three brain regions. We highlight a high-confidence set of independently validated genes differentially expressed between schizophrenia and control patients in the anterior cingulate cortex and integrate transcriptional changes with untargeted metabolite profiling.


Chromosomal mapping of repetitive DNAs in Gobionellus oceanicus and G. stomatus (Gobiidae; Perciformes): A shared XX/XY system and an unusual distribution of 5S rDNA sites on the Y chromosome.
With nearly 2,000 species, Gobiidae is the most specious family of the vertebrates. This high level of speciation is accompanied by conspicuous karyotypic modifications, where the role of repetitive sequences remains largely unknown. This study analyzed the karyotype of 2 species of the genus Gobionellus and mapped 18S and 5S ribosomal RNA genes and (CA)15 microsatellite sequences onto their chromosomes. G. oceanicus (2n = 56; ♂ 12 metacentrics (m) + 4 submetacentrics (sm) + 1 subtelocentric (st) + 39 acrocentrics (a); ♀ 12m + 4sm + 2st + 38a) and G. stomatus (2n = 56; ♂ 20m + 14sm + 1st + 21a; ♀ 20m + 14sm + 2st + 20a) possess the highest diploid chromosome number among the Gobiidae and have different karyotypes. Both species share an XX/XY sex chromosome system with a large subtelocentric X and a small acrocentric Y chromosome which is rich in (CA)15 sequences and bears 5S rRNA sites. Although coding and noncoding repetitive DNA sequences may be involved in the genesis or differentiation of the sex chromosomes, the exclusive presence of 5S rDNA sites on the Y, but not on the X chromosome of both species, represents a novelty in fishes. In summary, the karyotypic differences, as well as new data on the sex chromosome systems in these 2 Gobiidae species, confirm the high chromosomal dynamism observed in this family.


Defect Passivation through (α-Methylguanido)acetic Acid in Perovskite Solar Cell for High Operational Stability.
Defect passivation has become essential in improving efficiency and stability in perovskite solar cells. Here, we report the use of (α-methylguanido)acetic acid, also known as creatine, as a passivation molecule. It is employed both as an additive and as a surface passivation layer of perovskite thin films, given its multiple functional groups, which could address different defect sites, and its size, which could inherently affect the material structure. We prove that the surface passivation is more efficiently working by removing vulnerable defects on the surface. Hole and electron defect densities were reduced, leading to the highest power conversion efficiency of 22.6%. In addition, it can effectively protect the perovskite thin film and improve the operational stabilities in high thermal (85 °C) and humid conditions (50% relative humidity), suggesting a strong stability of the surface passivation layer.


Demographic decomposition of the marriage market in England and Wales 1911-1991.
A method for decomposing partner availability into its demographic components (preferences, previous birth trends, migration and mortality, and structure by marital status) is presented and applied to marriage market estimates for selected census years 1911-91 in England and Wales. Preferences are a key component at the youngest ages. The role of other factors varies by age and time period. Contrary to widespread assumption, variation in cohort sizes resulting from past fertility trends is not the dominant contributor to partner availability during this period. Mortality and migration effects tend to be larger than the effect of birth trends and the two marital status components are generally the largest in size. Determinants of intercensal change are similar to the cross-sectional picture. Reasons for the modest contribution of trends in annual births are discussed. Cohort effects on partner supply are not necessarily absent but could arise through a number of mechanisms.


Variability of grain quality in sorghum: association with polymorphism in Sh2, Bt2, SssI, Ae1, Wx and O2.
To ensure food security in Africa and Asia, developing sorghum varieties with grain quality that matches consumer demand is a major breeding objective that requires a better understanding of the genetic control of grain quality traits. The objective of this targeted association study was to assess whether the polymorphism detected in six genes involved in synthesis pathways of starch (Sh2, Bt2, SssI, Ae1, and Wx) or grain storage proteins (O2) could explain the phenotypic variability of six grain quality traits [amylose content (AM), protein content (PR), lipid content (LI), hardness (HD), endosperm texture (ET), peak gelatinization temperature (PGT)], two yield component traits [thousand grain weight (TGW) and number of grains per panicle (NBG)], and yield itself (YLD). We used a core collection of 195 accessions which had been previously phenotyped and for which polymorphic sites had been identified in sequenced segments of the six genes. The associations between gene polymorphism and phenotypic traits were analyzed with Tassel. The percentages of admixture of each accession, estimated using 60 RFLP probes, were used as cofactors in the analyses, decreasing the proportion of false-positive tests (70%) due to population structure. The significant associations observed matched generally well the role of the enzymes encoded by the genes known to determine starch amount or type. Sh2, Bt2, Ae1, and Wx were associated with TGW. SssI and Ae1 were associated with PGT, a trait influenced by amylopectin amount. Sh2 was associated with AM while Wx was not, possibly because of the absence of waxy accessions in our collection. O2 and Wx were associated with HD and ET. No association was found between O2 and PR. These results were consistent with QTL or association data in sorghum and in orthologous zones of maize. This study represents the first targeted association mapping study for grain quality in sorghum and paves the way for marker-aided selection.


Quantification of cytoskeletal deformation in living cells based on hierarchical feature vector matching.
The cytoskeleton is a dynamic scaffold in living cells even in the absence of externally imposed forces. In this study on cytoskeletal deformation, the applicability of hierarchical feature vector matching (HFVM), a new matching method, currently applied in space research and three-dimensional surface reconstruction, was investigated. Stably transfected CHO-K1 cells expressing green fluorescent protein (GFP) coupled to vimentin were used to visualize spontaneous movement of the vimentin cytoskeleton of individual cells using a confocal laser scanning system. We showed that, with proper parameter and configuration settings, HFVM could recognize and trace 60-70% of all image points in artificially translated, rotated, or deformed images. If only points belonging to the cytoskeleton were selected for matching purposes, the percentage of matched points increased to 98%. This high percentage of recognition also could be reached in a time series of images, in which a certain degree of bleaching of the fluorescence over the recording time of 30 min was inevitable. In these images, HFVM allowed the detection as well as the quantification of spontaneous cytoskeletal movements of up to 10% of the cell width. Therefore, HFVM appears to be a reliable method of quantifying dynamic cytoskeletal behavior in living cells.


Naturopathy in Australia: Where are we now? Where are we heading?
Naturopathy is the general practice of natural therapies. It emphasizes prevention, treatment, and promotion of optimal health through therapeutic modalities which encourage the self-healing process of the body. Formalized in the 19th century by the hydrotherapy and nature cure movement in Austria and Germany, naturopathy was introduced to Australia at the turn of the 20th century. It became popular since the 1970s due to social and cultural change characterized by the post-modern philosophy, as well as government policies highlighting individual responsibility and freedom of choice. Naturopathy is one of the most popular forms of complementary medicine in Australia today with naturopaths received 4.9 million consultations annually. Naturopathic consultations are sought for a variety of conditions and, in some areas, as a form of primary care, especially by middle-aged women who have a higher education level and a higher annual income. The number of Australian naturopaths was estimated to be over 4000 in 2017 and expects to grow to over 4600 by 2022, although this number is likely to be an underestimation. Australian naturopaths, as a predominantly female profession, work mainly in private clinical practice with nutritional medicine, herbal medicine, homeopathy, as well as massage therapies being the most common modalities used. There are also signs of greater integration with community pharmacies and integrative medicine clinics in major cities. The Bachelor's degree programs in Naturopathy has just become the only accredited entry-level qualification since late 2015. Currently, there are only 5 private colleges offering naturopathic education, a far cry from the 40 over in mid-2000. The profession continues to be self-regulated. There is no barrier of entry to practice and unqualified practitioners of naturopathy can potentially do harm to the public. The registration of naturopaths remains unresolved due to fragmented representation under many professional associations, disunity among the profession, and objections by certain health care lobbyists. There is a dearth of research demonstrating efficacy of the whole practice of naturopathy in Australia, which has directed the government's decision to withdraw it from private health insurance coverage from 2019. Moving forward, the whole system research of naturopathy in Australia will be in focus with the recent establishment of a practice-based research network and an international research consortium. With increasing scrutiny from evidence-based medicine, the present and future challenge to Australian naturopaths is centered on the integration of both scientific and traditional evidence to form the foundation of a person-centered, evidence-informed practice.


The pitfalls of inferring virus-virus interactions from co-detection prevalence data: application to influenza and SARS-CoV-2.
There is growing experimental evidence that many respiratory viruses-including influenza and SARS-CoV-2-can interact, such that their epidemiological dynamics may not be independent. To assess these interactions, standard statistical tests of independence suggest that the prevalence ratio-defined as the ratio of co-infection prevalence to the product of single-infection prevalences-should equal unity for non-interacting pathogens. As a result, earlier epidemiological studies aimed to estimate the prevalence ratio from co-detection prevalence data, under the assumption that deviations from unity implied interaction. To examine the validity of this assumption, we designed a simulation study that built on a broadly applicable epidemiological model of co-circulation of two emerging or seasonal respiratory viruses. By focusing on the pair influenza-SARS-CoV-2, we first demonstrate that the prevalence ratio systematically underestimates the strength of interaction, and can even misclassify antagonistic or synergistic interactions that persist after clearance of infection. In a global sensitivity analysis, we further identify properties of viral infection-such as a high reproduction number or a short infectious period-that blur the interaction inferred from the prevalence ratio. Altogether, our results suggest that ecological or epidemiological studies based on co-detection prevalence data provide a poor guide to assess interactions among respiratory viruses.


Transcriptional changes in Manila clam (Ruditapes philippinarum) in response to Brown Ring Disease.
Brown Ring Disease (BRD) is a bacterial infection affecting the economically-important clam Ruditapes philippinarum. The disease is caused by a bacterium, Vibrio tapetis, that colonizes the edge of the mantle, altering the biomineralization process and normal shell growth. Altered organic shell matrices accumulate on the inner face of the shell leading to the formation of the typical brown ring in the extrapallial space (between the mantle and the shell). Even though structural and functional changes have been described in solid (mantle) and fluid (hemolymph and extrapallial fluids) tissues from infected clams, the underlying molecular alterations and responses remain largely unknown. This study was designed to gather information on clam molecular responses to the disease and to compare focal responses at the site of the infection (mantle and extrapallial fluid) with systemic (hemolymph) responses. To do so, we designed and produced a Manila clam expression oligoarray (15K Agilent) using transcriptomic data available in public databases and used this platform to comparatively assess transcriptomic changes in mantle, hemolymph and extrapallial fluid of infected clams. Results showed significant regulation in diseased clams of molecules involved in pathogen recognition (e.g. lectins, C1q domain-containing proteins) and killing (defensin), apoptosis regulation (death-associated protein, bcl-2) and in biomineralization (shell matrix proteins, perlucin, galaxin, chitin- and calcium-binding proteins). While most changes in response to the disease were tissue-specific, systemic alterations included co-regulation in all 3 tested tissues of molecules involved in microbe recognition and killing (complement-related factors, defensin). These results provide a first glance at molecular alterations and responses caused by BRD and identify targets for future functional investigations.


Treatment of a giant coronary artery aneurysm: intravascular ultrasound and optical coherence tomography findings.
A giant coronary aneurysm (GCA) partially thrombosed was demonstrated in a 77-year-old patient evaluated for an inferior myocardial infarction. Primary angioplasty (balloon only) with suboptimal result was initially obtained. After triple antiplatelet and anticoagulation therapy (4 days), a new angiography was performed and a fusiform GCA was clearly delineated. A second percutaneous intervention was performed using a "scaffolding technique" with conventional stent and subsequent implantation of 2 polytetrafluoroethylene-covered stents to successfully exclude the aneurysm. This case demonstrates a novel technique to treat long GCA.


A novel asymmetric 3D in-vitro assay for the study of tumor cell invasion.
The induction of tumor cell invasion is an important step in tumor progression. Due to the cost and slowness of in-vivo invasion assays, there is need for quantitative in-vitro invasion assays that mimic as closely as possible the tumor environment and in which conditions can be rigorously controlled. We have established a novel asymmetric 3D in-vitro invasion assay by embedding a monolayer of tumor cells between two layers of collagen. The cells were then allowed to invade the upper and lower layers of collagen. To visualize invading cells the gels were sectioned perpendicular to the monolayer so that after seeding the monolayer appears as a thin line precisely defining the origin of invasion. The number of invading tumor cells, their proliferation rate, the distance they traverse and the direction of invasion could then be determined quantitatively. The assay was used to compare the invasive properties of several tumor cell types and the results compare well with those obtained by previously described assays. Lysyl-oxidase like protein-2 (Loxl2) is a potent inducer of invasiveness. Using our assay we show for the first time that inhibition of endogenous Loxl2 expression in several types of tumor cells strongly inhibits their invasiveness. We also took advantage of the asymmetric nature of the assay in order to show that fibronectin enhances the invasiveness of breast cancer cells more potently than laminin. The asymmetric properties of the assay were also used to demonstrate that soluble factors derived from fibroblasts can preferentially attract invading breast cancer cells. Our assay displays several advantages over previous invasion assays as it is allows the quantitative analysis of directional invasive behavior of tumor cells in a 3D environment mimicking the tumor microenvironment. It should be particularly useful for the study of the effects of components of the tumor microenvironment on tumor cell invasiveness.


Possible association of radioprotective and chemoprotective aminophosphorothioate drug activity with polyamine oxidase susceptibility.
The aminophosphorothioate drug S-2-(3-aminopropylamino)ethylphosphorothioate (WR-2721) is both radioprotective and chemoprotective, with potential clinical use in cancer therapies. These distinct properties may be associated with its catabolism by polyamine oxidase (EC 188.8.131.52), which is found in varying amounts in different body tissues. Unfortunately, the metabolite is probably a cytotoxic aldehyde, but it should be detoxified in vivo following adduction with tissue sulfhydryls. Whether conversion and adduction benefit or hinder pharmacologic activity is not known, inasmuch as aldehydes may reduce oxygen-dependent free radicals generated by irradiation of tissues. S-2-(3-aminopropylamino)propylphosphorothioate was similarly a substrate for polyamine oxidase, and the product was cytotoxic. Other aminophosphorothioates [S-2-(4-aminobutaneamino)ethylphosphorothioate, S-2-(5-aminopentylamino)ethylphosphorothioate, and S-2-(4-aminobutaneamino)propylphosphorothioate] were poor substrates and less radioprotective.


AC-Electroosmosis-Assisted Surface Plasmon Resonance Sensing for Enhancing Protein Signals with a Simple Kretschmann Configuration.
A surface plasmon resonance (SPR) sensor chip fabricated with a comb-shaped microelectrode array to supply alternating current (AC) voltage is reported. The chip induces circulating flow near the surface (i.e., AC electroosmosis). The circulating flow provides a mixing effect, which enhances the binding of the analyte molecules. We evaluated the SPR characteristics of the chip and demonstrated an improvement in protein binding to the chip surface. SPR sensor chips with comb-shaped microelectrodes were fabricated using standard UV lithography. Sensing experiments were conducted using a standard Kretschmann-type SPR measurement system. To demonstrate the mixing effect of AC electroosmosis, we evaluated the binding of immunoglobulin G molecules onto the sensor surface where anti-immunoglobulin G antibodies were covalently immobilized. The result indicates that the amount of binding increases by a factor of 1.7 above that achieved by using a conventional chip, suggesting enhancement of the protein signal.


Treatment planning for brachytherapy: an integer programming model, two computational approaches and experiments with permanent prostate implant planning.
An integer linear programming model is proposed as a framework for optimizing seed placement and dose distribution in brachytherapy treatment planning. The basic model involves using 0/1 indicator variables to describe the placement or non-placement of seeds in a prespecified three-dimensional grid of potential locations. The dose delivered to each point in a discretized representation of the diseased organ and neighbouring healthy tissue can then be modelled as a linear combination of the indicator variables. A system of linear constraints is imposed to attempt to keep the dose level at each point to within specified target bounds. Since it is physically impossible to satisfy all constraints simultaneously, each constraint uses a variable to either record when the target dose level is achieved, or to record the deviation from the desired level. These additional variables are embedded into an objective function to be optimized. Variations on this model are discussed and two computational approaches--a branch-and-bound algorithm and a genetic algorithm--for finding 'optimal' seed placements are described. Results of computational experiments on a collection of prostate cancer cases are reported. The results indicate that both optimization algorithms are capable of producing good solutions within 5 to 15 min, and that small variations in model parameters can have a measurable effect on the dose distribution of the resulting plans.


Pulmonary Lymphoepithelioma-Like Carcinoma: A Mini-Review.
Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and distinct subtype of non-small-cell lung carcinoma associated with Epstein-Barr virus (EBV) infection. We systematically reviewed the recent research that expands our knowledge about PLELC, with main focus on its genetic profile, tumor-infiltrating environment, PD-L1 expression, circulating EBV-DNA, clinical utility of 18F-FDG PET/CT, and treatment strategy. A low frequency of typical driver mutations and widespread existence of copy number variations was detected in PLELC. Persistent EBV infection may trigger intense infiltration of lymphocytes, representing enhanced tumor immunity and possibly resulting in a better prognosis. Circulating EBV-DNA in the plasma of patients with PLELC may predict disease progression and response to therapy. PLELC is 18F-FDG avid, and 18F-FDG PET may help refine palliation strategies and subsequently improve the prognosis. Most of the reported patients present at early and resectable stage, and surgical resection with curative intent is the preferred approach. There is currently no consensus on the regimen of chemotherapy for patients with advanced stages. EGFR-targeted therapies seem to have no therapeutic effect, and the clinical impact of PD-1/PD-L1 therapy is uncertain but worthy of further research.


A research agenda to assure equity during periods of emergency department crowding.
The effect of emergency department (ED) crowding on equitable care is the least studied of the domains of quality as defined by the Institute of Medicine (IOM). Inequities in access and treatment throughout the health care system are well documented in all fields of medicine. While there is little evidence demonstrating that inequity is worsened by crowding, theory and evidence from social science disciplines, as well as known barriers to care for vulnerable populations, would suggest that crowding will worsen inequities. To design successful interventions, however, it is important to first understand how crowding can result in disparities and base interventions on these mechanisms. A research agenda is proposed to understand mechanisms that may threaten equity during periods of crowding and design and test potential interventions that may ensure the equitable aspect of quality of care.


[Topical problems of industrial ecology and prevention of occupational diseases].
Medical genetic studies established abnormal occupational markers and individual risk factors which all made it possible to develop the modes of prevention of occupational bronchopulmonary diseases resulted from exposure to fibrogenic and allergenic dust. A system of screening approach to preventing occupational respiratory diseases is proposed.


Polymerization Efficacy Affects the Long-term Mini-interfacial Fracture Toughness.
To evaluate the effect of the type and concentration of photo-initiator on the long-term bonding efficacy to dentin in terms of mini-interfacial fracture toughness (mini-iFT). The bonding efficacy of the one-step self-etch (SE) adhesive Clearfil S3 Bond Plus and four derivative experimental adhesives (Leuven University Bond [LUB]), which were similar in composition except for the (co)photo-initiators (all prepared by Kuraray Noritake), containing 2.0 wt% camphorquinone (CQ) and 2.0 wt% EDMAB (LUB-CQ/amine_high), 0.35 wt% CQ and 0.35 wt% EDMAB (LUB-CQ/amine_low ), 2.0 wt% TPO (LUB-TPO_high), and 0.35 wt% TPO (LUB-TPO_low), was measured using a mini-iFT approach after being aged for 6 months and 1 year by water storage at 37°C (control: 1 week mini-iFT). The mini-iFT specimens were loaded until failure in a 4-point bending device to determine the interfacial fracture toughness (KIc). All fractured specimens were evaluated using scanning electron microscopy (SEM). The mini-iFT of Clearfil S3 Bond Plus and the adhesives with high photo-initiator concentrations was not significantly different at 6 months, although it dropped significantly at 1 year. For each storage period, the mini-iFT of the adhesives with high photo-initiator concentrations was not significantly different from that of the commercial adhesive, in contrast to the significantly lower mini-iFT measured for adhesives with low concentrations of photo-initiator. SEM fracture analysis revealed that the adhesives with high concentrations of photo-initiator most frequently failed at the top of the hybrid layer at 1 week, while this failure pattern shifted to the bottom of the hybrid layer after aging. A one-step self-etch adhesive should contain photo-initiator in a sufficiently high concentration, as this directly improves its immediate and long-term bonding efficacy to dentin. While the mini-iFT remained stable up to 6 month of aging for both the commercial and the adhesive with a high concentration of photo-initiator, the mini-iFT was found to decrease after 1 year of aging.


Simultaneous enzymatic/electrochemical determination of glucose and L-glutamine in hybridoma media by flow-injection analysis.
A split-stream flow-injection analysis system is described for simultaneous determination of glucose and L-glutamine in serum-free hybridoma bioprocesses media. Amperometric measurement of glucose is based on anodic oxidation of hydrogen peroxide produced by immobilized glucose oxidase within a triple layer membrane of an integrated flow-through glucose-selective biosensor. Determination of L-glutamine is based on quantitating ammonium ions produced in a flow-through enzymes reactor containing immobilized glutaminase enzyme, and subsequent downstream potentiometric detection of these ions by a nonacting-based ion-selective polymer membrane electrode. Endogenous potassium and ammonium ion interference in the L-glutamine determination are eliminated by using a novel in-line tubular cation-exchange membrane unit to exchange these interferent species for cations undetectable by the membrane electrode. The first generation split-steam flow-injections system can assay 12 samples/h using direct injections of 50 microL of media samples, with linear responses to glucose in the range of 0.03 to 30 mM, and log-linear response to L-glutamine from 0.1 to 10 mM.


Efficient Algorithms for Estimating the Absorption Spectrum within Linear Response TDDFT.
We present a special symmetric Lanczos algorithm and a kernel polynomial method (KPM) for approximating the absorption spectrum of molecules within the linear response time-dependent density functional theory (TDDFT) framework in the product form. In contrast to existing algorithms, the new algorithms are based on reformulating the original non-Hermitian eigenvalue problem as a product eigenvalue problem and the observation that the product eigenvalue problem is self-adjoint with respect to an appropriately chosen inner product. This allows a simple symmetric Lanczos algorithm to be used to compute the desired absorption spectrum. The use of a symmetric Lanczos algorithm only requires half of the memory compared with the nonsymmetric variant of the Lanczos algorithm. The symmetric Lanczos algorithm is also numerically more stable than the nonsymmetric version. The KPM algorithm is also presented as a low-memory alternative to the Lanczos approach, but the algorithm may require more matrix-vector multiplications in practice. We discuss the pros and cons of these methods in terms of their accuracy as well as their computational and storage cost. Applications to a set of small and medium-sized molecules are also presented.


[Pulmonary Langerhans'-cell histiocytosis].
Pulmonary Langerhans'-cell histiocytosis belongs to a spectrum of diseases characterized by monoclonal proliferation and infiltration of organs by Langerhans' cells. It is an uncommon interstitial lung disease of unknown etiology occurring almost exclusively in cigarette smokers. It s course in adults is variable and unpredictable, ranging from benign self-limiting types with spontaneous regression to slowly progressive malignant disease that leads to respiratory failure and death. We report one patient diagnoses of pulmonary Langerhans' cell histiocytosis who experimented an objective radiographic improvement and disappearance of symptoms after smoking cessation.


A Community Level Sample Survey to Determine CurrentUnderstanding About Medical Recycling of Cardiovascular ImplantableElectronic Devices.
Medical recycling and reutilization of cardiovascular implantableelectronic devices (CIEDs) have a significant impact not only in patientsof low-income countries but may also in certain patients in the UnitedStates who do not have sufficient medical insurance coverage. Themain determining factor for future utility and popularity of recycledmedical devices is thorough understanding about this topic amongstpublic and healthcare professional. To the best of our knowledge,there has been no study conducted so far at a community level to determinethe understanding in public and healthcare personnel about recyclingof medical devices including CIEDs. We sought to determine existingknowledge and attitude about recycling of CIEDs amongst representativesample population in a community. A questionnaire was sent for online completion to multiple peoplein the community, healthcare and funeral home in Lehigh Valley, Pennsylvania,USA. The questionnaire was designed in order to assess three maincategories; knowledge, attitude and practice. We called this a KAPstudy which is an acronym for knowledge, attitude and practice survey. We got 117 responses to our questionnaire from community members(55.45%), 89 responses (42.18%) from the healthcare personnel andfive responses (2.37%) from funeral homes. About 30.77% communityparticipants had heard about medical devices recycling compared to57.30% participants from healthcare sector. A total of 88.64% of medicalprofessionals were aware that there are people in the world who diebecause they cannot afford CIEDs while 73.50% of community participantswere also found to be aware of this fact. Higher percentages of healthcareprofessionals were found to be willing to personally consider a decisionabout medical device donation compared to community participants. CIED reutilization can improve quality of life among many patientswith low or medium socioeconomic status. People should be made moreaware about the benefits of CIED reutilization. Concerns about device-relatedinfections, complications and law suits should be addressed to helpimprove their utility.


Influence of murine renal sexual dimorphism on amiloride-induced hyperkalemia.
The present study investigated the influence of androgens in potassium homeostasis both under normal conditions and when potassium balance was affected by the mild diuretic amiloride. Our results indicate the existence of a clear sexual dimorphism in renal and plasma potassium content in CD1 mice, adult males having a higher plasma potassium concentration than females or 40-day-old male mice (4.6 +/- 1.0 vs. 3.9 +/- 0.9 mEq/l). Plasma K(+) concentration was increased by testosterone treatment and decreased after orchiectomy, while the opposite occurred in the case of renal potassium concentration. Amiloride was well tolerated by CD1 female mice, but induced severe hyperkalemia in male mice, where it was also associated with a high rate of mortality. Testosterone treatment increased the toxicity of the diuretic in both CD1 female and male mice. Histopathological analysis of kidneys from CD1 male mice treated with amiloride revealed alterations at the proximal and distal tubule level. These results strongly suggest that androgens may produce adverse effects in renal function.


Changes in choriocapillaris and retinal pigment epithelium in age-related macular degeneration.
Retinal pigment epithelial cells (RPE) and the choriocapillaris are on opposite sides of Bruch's membrane and control transport in and out of the retina. In age-related macular degeneration (AMD), they may also be responsible for deposition of material in and on Bruch's membrane and the formation or regression of choroidal neovascularization (CNV). Indocyanine green (ICG) angiography can be used to visualize the choroidal vasculature and CNV. Filling of the choriocapillaris with ICG was delayed in subjects older than 50 years of age, and areas of hypofluorescence were observed in maculas of AMD subjects, often associated with CNV. Laser Doppler flowmetry of the choriocapillaris in the macula demonstrated that choroidal blood flow and volume are reduced in subjects older than 46 years of age and further decreased in subjects with AMD. The human choriocapillaris can be histologically studied in two dimensions by incubating the tissue for alkaline phosphatase activity, flat-embedding it in transparent polymer and sectioning it. Using this technique, choriocapillaris dropout was found to be associated with deposition of material in Bruch's membrane in diabetic subjects. When RPE are removed from Bruch's membrane, the choriocapillaris degenerates; the regeneration of choriocapillaris can be blocked by Genistein, a tyrosine kinase inhibitor. Finally, RPE cells may produce substances that both stimulate the formation and regression of CNV in animal models. These studies suggest that there may be a reduction in choriocapillaris flow in AMD, and this loss of choriocapillaris can be associated with the Bruch's membrane deposits that are hallmarks of AMD. Furthermore, RPE may stimulate the formation and regression of CNV and RPE loss can result in loss of choriocapillaris.


Association of the nibrin gene (NBN) variants with breast cancer.
Nibrin, encoded by the NBN gene, participates in DNA repair. Mutations in the NBN gene lead to Nijemen breakage syndrome, which may result in several types of diseases, particularly susceptibility to cancer, including breast cancer. Polymorphic variants and defective mutations occurring in the NBN gene increase the risk of breast cancer through the double-stranded break repair mechanism. The aim of the present study was to investigate a possible association between breast cancer and NBN genetic variants, NBN 924 T>C, 8360 G>C and 30537 G>C, in women with breast cancer. Locus-specific primers were designed to study 3 genetic variants in DNA samples isolated from peripheral blood samples of 101 women with breast cancer and 115 healthy controls. Subsequently, 3 polymerase chain reaction-restriction fragment length polymorphism methods were performed and the obtained results were statistically analysed. The NBN gene 924 T>C variant was found to be significantly associated with breast cancer (χ2=5.722, P=0.017). There were no statistically significant differences between cases and controls in the NBN gene 8360 G>C variant (χ2=1,125, P=0.570) or the NBN gene 30537 G>C variant (χ2=4.301, P=0.116). In conclusion, the NBN gene 924 T>C variant may be a genetic risk factor for breast cancer development in women with breast cancer.


Gradual release of strongly bound nitric oxide from Fe₂(NO)₂(dobdc).
An iron(II)-based metal-organic framework featuring coordinatively unsaturated redox-active metal cation sites, Fe2(dobdc) (dobdc(4-) = 2,5-dioxido-1,4-benzenedicarboxylate), is shown to strongly bind nitric oxide at 298 K. Adsorption isotherms indicate an adsorption capacity greater than 16 wt %, corresponding to the adsorption of one NO molecule per iron center. Infrared, UV-vis, and Mössbauer spectroscopies, together with magnetic susceptibility data, confirm the strong binding is a result of electron transfer from the Fe(II) sites to form Fe(III)-NO(-) adducts. Consistent with these results, powder neutron diffraction experiments indicate that NO is bound to the iron centers of the framework with an Fe-NO separation of 1.77(1) Å and an Fe-N-O angle of 150.9(5)°. The nitric oxide-containing material, Fe2(NO)2(dobdc), steadily releases bound NO under humid conditions over the course of more than 10 days, suggesting it, and potential future iron(II)-based metal-organic frameworks, are good candidates for certain biomedical applications.


Validity of automated threshold audiometry in school aged children.
Automated hearing tests have the potential to reduce the burden of disease amongst learners by introducing such services within the school context. The aim of the study was to conduct a validation study on normal and hearing impaired learners, comparing air and bone conduction automated test results to conventional test results in 50 school aged learners (n = 100 ears) within a noise controlled school environment using a cross sectional comparative study design. The KuduWave 5000 (Emoyo.net) was used in this study. The spearman's correlation coefficient was calculated to determine test-retest reliability. The mean and standard deviation (SD) was measured for each frequency. The absolute mean difference (AMD) and SD was calculated for both air and bone conduction testing at each frequency for automated testing. A paired sampled t-test and a one way ANOVA was used to identify any significant differences. Alpha was set as 0.05. There was significant correlation between thresholds obtained for automated test one and test two for normal hearing and hearing impaired group. The spearmans correlation coefficient was high (close to +1) for majority of the results for both groups across the frequency range. Both air and bone conduction testing across the frequency range of 250 Hz-2000 Hz and at 8000 Hz were not statistically signfiicant (p < .005) for both groups, however at 4000 Hz for bone conduction testing in the hearing impaired group, there was a statisticially signficant difference (p = .003). This was attirubted to the variaibilty in bone conduction test results often due to force and placement of the bone vibrator. The findings indicate that automated audiometry can yield relaible results that are comparable to conventional test results. Key clinical considerations include extending the response time, regular rest periods, improving instructions and comfort levels.


X-radiography front tracking gradient furnace for directional solidification of bulk Al-alloys.
A unique gradient furnace for directional solidification experiments with bulk Al-alloy samples developed at German Aerospace Center is presented. It allows for in situ process control in solidifying samples by using x-radiography, and further insight into the solidification process is gained in combination with x-ray computational tomography on the solidified samples. Tracking of interfaces during directional solidification of bulk samples via in situ x-radiography (TIREX) enables the investigation of the melting process and observation of the movement of the entire mushy zone through the sample, tracing the solid-liquid interface during directional solidification and correlating the observations with the microstructure of the samples. Monitoring the temperature profile inside the sample by in situ observation of the length of the mushy zone is particularly important because the temperature gradient G and the rate of interfacial growth v determine the microstructure of solidification. The x-radiography setup offers temporal and spatial resolutions of 0.5 s and 70 μm, respectively, with a field of view of 10 × 50 mm2. Constant solidification velocities of up to 0.15 mm s-1 at a temperature gradient of up to 8 K mm-1 can be achieved in a temperature range of 537-1373 K. A flat solid-liquid interface inside a rod-like sample with 5 mm diameter is achieved by surrounding the sample by thermal isolating graphite foam. Performance tests with hypoeutectic Al-10 wt. % Cu alloy samples show the functionality of the furnace facility.


Adaptation to stress in yeast: to translate or not?
For most eukaryotic organisms, including Saccharomyces cerevisiae, the rapid inhibition of protein synthesis forms part of a response to stress. In order to balance the changing conditions, precise stress-specific alterations to the cell's proteome are required. Therefore, in the background of a global down-regulation in protein synthesis, specific proteins are induced. Given the level of plasticity required to enable stress-specific alterations of this kind, it is surprising that the mechanisms of translational regulation are not more diverse. In the present review, we summarize the impact of stress on translation initiation, highlighting both the similarities and distinctions between various stress responses. Finally, we speculate as to how yeast cells generate stress-responsive programmes of protein production when regulation is focused on the same steps in the translation pathway.


The impact of temperature and urinary constituents on urine viscosity and its relevance to bladder hyperthermia treatment.
The aim of this study was to determine the kinematic viscosity of human urine and factors associated with its variability. This value is necessary for accurate modelling of fluid mechanics and heat transfer during hyperthermia treatments of bladder cancer. Urine samples from 64 patients undergoing routine clinical testing were subject to dipstick urinalysis and measurement of viscosity with a Cannon-Fenske viscometer. Viscosity measurements were taken at relevant temperatures for hyperthermia studies: 20 °C (room temperature), 37 °C (body temperature), and 42 °C (clinical hyperthermia temperature). Factors that might affect viscosity were assessed, including glucosuria, haematuria, urinary tract infection status, ketonuria and proteinuria status. The correlation of urine specific gravity and viscosity was measured with Spearman's rho. Urine kinematic viscosity at 20 °C was 1.0700 cSt (standard deviation (SD) = 0.1076), at 37 °C 0.8293 cSt (SD = 0.0851), and at 42 °C 0.6928 cSt (SD = 0.0247). Proteinuria appeared to increase urine viscosity, whereas age, gender, urinary tract infection, glucosuria, ketonuria, and haematuria did not affect it. Urine specific gravity was only modestly correlated with urine viscosity at 20 °C (rho = 0.259), 37 °C (rho = 0.266), and 42 °C (rho = 0.255). The kinematic viscosity of human urine is temperature dependent and higher than water. Urine specific gravity was not a good predictor of viscosity. Of factors that might affect urine viscosity, only proteinuria appeared to be clinically relevant. Estimates of urine viscosity provided in this manuscript may be useful for temperature modelling of bladder hyperthermia treatments with regard to correct prediction of the thermal conduction effects.


Pediatric pharmacoepidemiology - safety and effectiveness of medicines for ADHD.
Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder in children and adolescents that comprises core symptoms of developmentally inappropriate levels of inattention and/or hyperactivity and impulsivity. Stimulant (methylphenidate, amphetamines) and non stimulant (atomoxetine, clonidine and guanfacine) are the treatment usually prescribed for ADHD. Area covered: This review covers the safety of ADHD medications in children and adolescents. MEDLINE, EMBASE and PsycINFO databases were searched with the aim to retrieve prospective studies that monitored the incidence of adverse events (AEs) in children receiving drug therapy for ADHD. Many of the studies investigated the risk of specific AEs. In particular, the cardiovascular safety, the impact on growth and on sleep pattern, the risk of substance use disorders and of suicidal ideation are among the topics more studied. Expert opinion: Effective drugs for ADHD appears to be safe and well tolerated. Most of the adverse events reported in the randomised controlled trials are mild and transient. Decreased appetite, growth decrease and the impact on sleep (insomnia for stimulants and somnolence for alpha2-agonists) are among the most common events. Concerns exist about cardiovascular and psychiatric AEs, even if the available evidence does not support an association with medications.


An integrative study of five biological clocks in somatic and mental health.
Biological clocks have been developed at different molecular levels and were found to be more advanced in the presence of somatic illness and mental disorders. However, it is unclear whether different biological clocks reflect similar aging processes and determinants. In ~3000 subjects, we examined whether five biological clocks (telomere length, epigenetic, transcriptomic, proteomic, and metabolomic clocks) were interrelated and associated to somatic and mental health determinants. Correlations between biological aging indicators were small (all r < 0.2), indicating little overlap. The most consistent associations of advanced biological aging were found for male sex, higher body mass index (BMI), metabolic syndrome, smoking, and depression. As compared to the individual clocks, a composite index of all five clocks showed most pronounced associations with health determinants. The large effect sizes of the composite index and the low correlation between biological aging indicators suggest that one's biological age is best reflected by combining aging measures from multiple cellular levels.


Tryptophan operon regulation in interspecific hybrids of enteric bacteria.
We examined tryptophan regulation in merodiploid hybrids in which a plasmid carrying the trp operon of Escherichia was introduced into Trp mutants of other enteric genera, or in which a plasmid carrying the trpR+ (repressor) gene of E. coli was transfered into fully constitutive trpR mutants of other genera. In these hybrids the trp operon of one species is controlled by the repressor of a different species. Similar investigations were possible in transduction hybrids in which either the trp operon or the trpR+ locus of Shigella dysenteriae was introduced into E. coli. Our measurements of trp enzymes levels in repressed and nonrepressed cells indicate that Trp regulation is normal, with only minor quantitative variations, in hybrids between E coli and Shigella dysenteriae, Salmonella typhimurium, Klebsiella aerogenes, Serratia marcescens, and Proteus mirabilis. Our results support the idea that a repressor-operator mechanism for regulating trp messenger ribonucleic acid production evolved in a common ancestor of the enteric bacteria, and that this repressor-operator recognition has been conversed during the evolutionary divergence of the Enterobacteriaceae.


A new method to determine joint range of movement and stiffness in rheumatoid arthritic patients.
Rheumatoid arthritis affects 0.5-1% of the general population. The prediction and prognosis of the disease varies for each individual and its course can detrimentally affect the psychosocial condition of the patient. Clinicians and Therapists aim to quickly diagnose and treat those with this debilitating disease. Detection relies heavily on manual evaluation methods that are dependent on training and can vary between observers. Angle measuring instrument, tape measure and grip strength dynamometer are used to assess the joint range and strength of a patient to determine their hand function. Joint stiffness can be a determining factor when diagnosing the advancement and improvement of Rheumatoid Arthritis (RA). This paper outlines the development of a hand movement measurement tool to accurately quantify patients' flexion, extension, abduction and adduction movement of each finger joint and quantifies the symptom of "early morning stiffness". It also describes the problems that arise when using a data glove to accurately measure Range Of Movement and discusses alternative methods to overcome these issues.


Friction coefficient of skin in real-time.
Friction studies are useful in quantitatively investigating the skin surface. Previous studies utilized different apparatuses and materials for these investigations but there was no real-time test parameter control or monitoring. Our studies incorporated the commercially available UMT Series Micro-Tribometer, a tribology instrument that permits real-time monitoring and calculation of the important parameters in friction studies, increasing the accuracy over previous tribology and friction measurement devices used on skin. Our friction tests were performed on four healthy volunteers and on abdominal skin samples. A stainless steel ball was pressed on to the skin with at a pre-set load and then moved across the skin at a constant velocity of 5 mm/min. The UMT continuously monitored the friction force of the skin and the normal force of the ball to calculate the friction coefficient in real-time. Tests investigated the applicability of Amonton's law, the impact of increased and decreased hydration, and the effect of the application of moisturizers. The friction coefficient depends on the normal load applied, and Amonton's law does not provide an accurate description for the skin surface. Application of water to the skin increased the friction coefficient and application of isopropyl alcohol decreased it. Fast acting moisturizers immediately increased the friction coefficient, but did not have the prolonged effect of the slow, long lasting moisturizers. The UMT is capable of making real-time measurements on the skin and can be used as an effective tool to study friction properties. Results from the UMT measurements agree closely with theory regarding the skin surface.


Human bovine tuberculosis - remains in the differential.
Mycobacterium bovis is a pathogen of cattle. The unpasteurized milk of affected cattle is a source of infection in humans. Despite the screening of cattle and the pasteurization of milk, M bovis has not been eradicated. A high index of clinical suspicion is needed in symptomatic patients with a history of possible exposure. At risk groups include animal workers, farmers, meat packers, vets and zoo keepers. Humans are usually infected by the aerosol route. We present two cases of human bovine tuberculosis. One was a presumptive case and the second was a confirmed case. Both responded well to antituberculous therapy. In the confirmed case, there was evidence of transmission to the partner living in the same house. Rifampicin prophylaxis was given to the exposed case. The M. bovis from the confirmed case was isoniazid resistant, in addition to having the well known resistance to pyrazinamide. Isoniazid resistance has been described before in those who are immunocompromised. We describe it in an immunocompetent patient.


Synthesis of precision antibody conjugates using proximity-induced chemistry.
Rationale: Therapeutic antibody conjugates allow for the specific delivery of cytotoxic agents or immune cells to tumors, thus enhancing the antitumor activity of these agents and minimizing adverse systemic effects. Most current antibody conjugates are prepared by nonspecific modification of antibody cysteine or lysine residues, inevitably resulting in the generation of heterogeneous conjugates with limited therapeutic efficacies. Traditional strategies to prepare homogeneous antibody conjugates require antibody engineering or chemical/enzymatic treatments, processes that often affect antibody folding and stability, as well as yield and cost. Developing a simple and cost-effective way to precisely couple functional payloads to native antibodies is of great importance. Methods: We describe a simple proximity-induced antibody conjugation method (pClick) that enables the synthesis of homogeneous antibody conjugates from native antibodies without requiring additional antibody engineering or post-synthesis treatments. A proximity-activated crosslinker is introduced into a chemically synthesized affinity peptide modified with a bioorthogonal handle. Upon binding to a specific antibody site, the affinity peptide covalently attaches to the antibody via spontaneous crosslinking, yielding an antibody molecule ready for bioorthogonal conjugation with payloads. Results: We have prepared well-defined antibody-drug conjugates and bispecific small molecule-antibody conjugates using pClick technology. The resulting conjugates exhibit excellent in vitro cytotoxic activity against cancer cells and, in the case of bispecific conjugates, superb antitumor activity in mouse xenograft models. Conclusions: Our pClick technology enables efficient, simple, and site-specific conjugation of various moieties to the existing native antibodies. This technology does not require antibody engineering or additional UV/chemical/enzymatic treatments, therefore providing a general, convenient strategy for developing novel antibody conjugates.


The induction of labour with prostaglandin F2alpha by intravenous infusion. II. A comparison of fetal and maternal acid-base values with those found in oxytocin induced labour and in spontaneous labour.
Serial determination of fetal and maternal pH, Pco2 and BDECF was performed in 34 cases of labour inductions with intravenously administered prostaglandin F2alpha or oxytocin. These values were compared with those found in ten cases of spontaneous labour. With the exception of eight cases of "high risk pregnancies" all the remaining parturients were healthy and within the 38th to 42nd week of gestation. With regard to the cases of "uncomplicated" pregnancies the general patterns of the acid-base changes were very similar in the three groups. The BDECF values in fetal scalp blood, however, showed a more marked tendency to increase in the group induced with prostaglandin. Further analysis of this group revealed that the rise of BDECF values could be attributed to cases with episodes of uterine hypertonus or signs of uterine incoordination. In the "high risk" pregnancy group the pH values in fetal scalp blood were lower and the BDECF values higher than in the group of "normal" pregnancy cases. The general pattern and the magnitude of the acid-base changes do not seem to be influenced by the administration of oxytocin or prostaglandin F2alpha as induction agents providing uterine activity is normal. Abnormal uterine activity, initiated by any of the two induction agents, is, however, associated with an increased risk of fetal acidosis.


The effect of electrical stimulation on corticospinal excitability is dependent on application duration: a same subject pre-post test design.
In humans, corticospinal excitability is known to increase following motor electrical stimulation (ES) designed to mimic a voluntary contraction. However, whether the effect is equivalent with different application durations and whether similar effects are apparent for short and long applications is unknown. The aim of this study was to investigate whether the duration of peripheral motor ES influenced its effect on corticospinal excitability. The excitability of the corticomotor pathway to abductor pollicis brevis (APB) was measured in fourteen health subjects using transcranial magnetic stimulation before, immediately after and 10 minutes after three different durations (20-, 40-, 60-min) of motor ES (30Hz, ramped). This intervention was designed to mimic a voluntary contraction in APB. To control for effects of motor ES on the peripheral elements (muscle fibre, membrane, neuromuscular junction), maximum compound muscle actions potentials (M-waves) were also recorded at each time point. Results were analysed using a repeated measures analysis of variance. Peripheral excitability was reduced following all three motor ES interventions. Conversely, corticospinal excitability was increased immediately following 20- and 40-min applications of motor ES and this increase was maintained at least 20-min following the intervention. A 60-min application of motor ES did not alter corticospinal excitability. A 20-min application of motor ES that is designed to mimic voluntary muscle contraction is as effective as that applied for 40-min when the aim of the intervention is to increase corticospinal excitability. Longer motor ES durations of 60-min do not influence corticospinal excitability, possibly as a result of homeostatic plasticity mechanisms.


The Impact of COVID-19 Pandemic on the Learning Outcomes of Medical Students in Taiwan: A Two-Year Prospective Cohort Study of OSCE Performance.
To avoid the negative impacts of the COVID-19 pandemic on clinical clerkship, supplemental teachings such as digital materials in the scenario-based distal simulations were implemented. This study utilized the OSCE (objective-structured clinical examination) to evaluate the impact of COVID-19 pandemic on the learning outcome of medical students from the regular group (class of 2020) and pandemic-impacted group (class of 2021). All medical students serially took, firstly, the mock-OSCE, secondly, the mock-OSCE, and the national OSCE. Then, the serial OSCE scores were compared between groups. Although with similar scores in the first mock OSCE, the regular group (n = 78) had a higher average score in the national OSCE than the pandemic-impacted group (n = 80) (872.18 vs. 834.96, p = 0.003). In terms of improvement, the performances of the regular group were also better than the pandemic-impacted group between the second mock OSCE and the national OSCE (79.10 vs. 38.14, p = 0.014), and between the second mock OSCE and the national OSCE (125.11 vs. 77.52, p = 0.003). While separating distinct genres, the regular group had more of a score increment in standardized patient-based stations between the second mock OSCE and the national OSCE (regular vs. pandemic-impacted: 57.03 vs. 18.95, p = 0.003), as well as between the first mock OSCE and the national OSCE (75.97 vs. 26.36, p < 0.001), but there was no significant difference among the skill-based stations. In particular, the scores of the emergency medicine associated station in the national OSCE of the pandemic-impacted group was lower. Our study implies that the pandemic significantly hampered the learning outcomes of final year medical students in their clinical participation. Especially facing the COVID-19 pandemic, more supplemental teachings are needed to compensate the decreasing emergency medicine exposure.


Hormone replacement therapy and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.
Hormone replacement therapy (HRT) is commonly prescribed to alleviate the climacteric symptoms of menopause. Recent findings from the Women's Health Initiative has raised questions about the routine use of HRT due to the increased observed incidence of cardiovascular disease and of breast and ovarian cancers in the treatment arm of the trial. In the general population, the association between HRT use and risk of ovarian cancer has not yet been resolved. This association has not been evaluated in BRCA1 or BRCA2 mutation carriers who face very high lifetime risks of both breast and ovarian cancers. We conducted a matched case-control study on 162 matched sets of women who carry a deleterious mutation in either the BRCA1 or BRCA2 gene. Women who had been diagnosed with ovarian cancer were matched to control subjects by mutation, year of birth, and age at menopause. Information on HRT use was derived from a questionnaire routinely administered to women who were found to be carriers of a mutation in either gene. Conditional logistic regression was used to estimate the association between HRT use and the risk of ovarian cancer, stratified by mutation status and type of HRT. Compared with those who had never used HRT, the odds ratio associated with ever use of HRT was 0.93 (95% CI = 0.56-1.56). There was no significant relationship with increasing duration of HRT use. There was a suggestion that progestin-based HRT regimens might protect against ovarian cancer (odds ratio = 0.57) but this association was not statistically significant (P = 0.20). HRT use does not appear to adversely influence the risk of ovarian cancer in BRCA mutation carriers.


[Malignant peripheral nerve sheath tumor with perineural differentiation (malignant perineurinoma) of the cervix uteri].
The paper describes a case of a malignant peripheral nerve sheath tumor with perineural differentiation and at the rare site of the cervix uteri in a 57-year-old patient. The diagnosis was established on the basis of extensive immunohistochemical examination, by excluding the similar neoplasms and detecting an immunophenotype characteristic of perineural differentiation. There are data available in the literature on the morphological and immunophenotypical characteristics of this tumor.


Atrial fibrillation in acute pulmonary embolism: prognostic considerations.
Although it is accepted that atrial fibrillation (AF) may be both the contributing factor and the consequence of pulmonary embolism (PE), data on the prognostic role of AF in patients with acute venous thromboembolism are scarce. Our aim was to study whether AF had a prognostic role in patients with acute PE. Retrospective cohort study involving 270 patients admitted for acute PE. Collected data: past medical history, analytic/gasometric parameters, admission ECG and echocardiogram, thoracic CT angiography. Patients followed for 6 months. An analysis was performed in order to clarify whether history of AF, irrespective of its timing, helps predict intrahospital, 1-month and 6-month all-cause mortality. Patients with history of AF, irrespective of its timing (n=57, 21.4%), had higher intrahospital (22.8% vs 13.1%, p=0.052, OR 2.07, 95% CI 0.98 to 4.35), 1-month (35.1% vs 16.9%, p=0.001, OR 3.16, 95% CI 1.61 to 6.21) and 6-month (45.6% vs 17.4%, p<0.001, OR 4.67, 95% CI 2.37 to 9.21) death rates. The prognostic power of AF was independent of age, NT-proBNP values, renal function and admission blood pressure and heart rate and additive to mortality prediction ability of simplified PESI (AF: p=0.021, OR 2.31, CI 95% 1.13 to 4.69; simplified PESI: p=0.002, OR 1.47, CI 95% 1.15 to 1.89). The presence of AF at admission added prognostic value to previous history of AF in terms of 1-month and 6-month all-cause mortality prediction, although it did not increase risk for intrahospital mortality. The presence of AF, irrespective of its timing, may independently predict mortality in patients with acute PE. These data should be tested and validated in prospective studies using larger cohorts.


Establishing a national chronic kidney disease surveillance system for the United States.
Despite the recognized importance of chronic kidney disease (CKD), the United States currently lacks a comprehensive, systematic surveillance program that captures and tracks all aspects of CKD in the population. As part of its CKD Initiative, the Centers for Disease Control and Prevention (CDC) funded two teams to jointly initiate the development of a CKD surveillance system. Here, we describe the process and methods used to establish this national CDC CKD Surveillance System. The major CKD components covered include burden (incidence and prevalence), risk factors, awareness, health consequences, processes and quality of care, and health system capacity issues. Goals include regular reporting of the data collected, plus development of a dynamic project web site and periodic issuance of a CKD fact sheet. We anticipate that this system will provide an important foundation for widespread efforts toward primary prevention, earlier detection, and implementation of optimal disease management strategies, with resultant increased awareness of CKD, decreased rates of CKD progression, lowered mortality, and reduced resource utilization. Final success will be measured by usage, impact, and endorsement.


Recognition and management of occlusal disease from a hygienist's perspective.
Dental disease can be described as a permanent alteration of loss or function of those parts generally cared for by dentists. Specifically, these include the teeth, periodontal tissues and associated dental structures. Historically the breakdown and subsequent loss of tooth structure was caused by dental caries. It has also been observed that tooth loss can result from overuse-abuse referred to as bruxism or bruxamania.


[Sexually transmissible disorders in allochtonous population groups; a pilot study].
In the registration of sexually transmitted diseases (STD) carried out by the nursing staff in the STD clinics the share of the immigrant populations of Turkish, Moroccan, Surinam and Antilles origin was investigated for the period 1986-89. In the total population of STD patients the immigrants appear to be overrepresented. Their share has increased from one-eight to one-fifth of the total number of STD cases. The STD rates (number of cases per 1000) for the Turkish and Moroccan populations are high, even after adjusting for population size and age. High STD rates are most apparent among males, especially among Turkish males. In comparison with the Dutch population more gonorrhoea is found among immigrants, in particular penicillinase producing Neisseria gonorrhoeae (PPNG). Turkish males (and prostitutes) contributed much to this relatively high prevalence. Further research is to be initiated in order to obtain better insight into the occurrence of STD among immigrant populations in The Netherlands, especially in connection with a potentially increased risk of infection with Human Immunodeficiency Virus (HIV).


Environmental Reservoirs of Nosocomial Infection: Imputation Methods for Linking Clinical and Environmental Microbiological Data to Understand Infection Transmission.
The transmission of hospital-acquired Carbapenem-resistant Enterobacteriaceae (CRE) is a serious and growing concern in hospitals worldwide. Previous research of CRE found that traditional patient-to-patient transmission of the bacteria does not fully account for all cases of transmission. Recent efforts to further understand modes of transmission found identical genomes of CRE in patient sinks as was found in cultures collected from patients, indicating that environmental reservoirs could be playing a larger role in transmission than was first realized. This study evaluated imputation methods for linking multiscale clinical and environmental microbiological data. We then utilized the imputed data set to model the risk of CRE presence in sinks between culture dates. We demonstrated that imputation based on expert knowledge of the unique factors of the physical hospital layout and patterns of occurrence throughout hospital sinks provided the best representation of sink positivity and also identified several significant risk factors for explaining environmental contamination. This work helps to more clearly define the mechanism and risk of transmission from a wastewater source to hospitalized patients in a world with increasingly antibiotic-resistant bacteria which can thrive in wastewater environments and cause infections in vulnerable patients.


TaijiGNN: A New Cycle-Consistent Generative Neural Network for High-Quality Bidirectional Transformation between RGB and Multispectral Domains.
Since multispectral images (MSIs) and RGB images (RGBs) have significantly different definitions and severely imbalanced information entropies, the spectrum transformation between them, especially reconstructing MSIs from RGBs, is a big challenge. We propose a new approach, the Taiji Generative Neural Network (TaijiGNN), to address the above-mentioned problems. TaijiGNN consists of two generators, G_MSI, and G_RGB. These two generators establish two cycles by connecting one generator's output with the other's input. One cycle translates the RGBs into the MSIs and converts the MSIs back to the RGBs. The other cycle does the reverse. The cycles can turn the problem of comparing two different domain images into comparing the same domain images. In the same domain, there are neither different domain definition problems nor severely underconstrained challenges, such as reconstructing MSIs from RGBs. Moreover, according to several investigations and validations, we effectively designed a multilayer perceptron neural network (MLP) to substitute the convolutional neural network (CNN) when implementing the generators to make them simple and high performance. Furthermore, we cut off the two traditional CycleGAN's identity losses to fit the spectral image translation. We also added two consistent losses of comparing paired images to improve the two generators' training effectiveness. In addition, during the training process, similar to the ancient Chinese philosophy Taiji's polarity Yang and polarity Yin, the two generators update their neural network parameters by interacting with and complementing each other until they all converge and the system reaches a dynamic balance. Furthermore, several qualitative and quantitative experiments were conducted on the two classical datasets, CAVE and ICVL, to evaluate the performance of our proposed approach. Promising results were obtained with a well-designed simplistic MLP requiring a minimal amount of training data. Specifically, in the CAVE dataset, to achieve comparable state-of-the-art results, we only need half of the dataset for training; for the ICVL dataset, we used only one-fifth of the dataset to train the model, but obtained state-of-the-art results.