Hierarchical analysis of genetic structure in the habitat-specialist Eastern Sand Darter (Ammocrypta pellucida).
Quantifying spatial genetic structure can reveal the relative influences of contemporary and historic factors underlying localized and regional patterns of genetic diversity and gene flow - important considerations for the development of effective conservation efforts. Using 10 polymorphic microsatellite loci, we characterize genetic variation among populations across the range of the Eastern Sand Darter (Ammocrypta pellucida), a small riverine percid that is highly dependent on sandy substrate microhabitats. We tested for fine scale, regional, and historic patterns of genetic structure. As expected, significant differentiation was detected among rivers within drainages and among drainages. At finer scales, an unexpected lack of within-river genetic structure among fragmented sandy microhabitats suggests that stratified dispersal resulting from unstable sand bar habitat degradation (natural and anthropogenic) may preclude substantial genetic differentiation within rivers. Among-drainage genetic structure indicates that postglacial (14 kya) drainage connectivity continues to influence contemporary genetic structure among Eastern Sand Darter populations in southern Ontario. These results provide an unexpected contrast to other benthic riverine fish in the Great Lakes drainage and suggest that habitat-specific fishes, such as the Eastern Sand Darter, can evolve dispersal strategies that overcome fragmented and temporally unstable habitats.


A Lifespan Approach to Patient-Reported Outcomes and Quality of Life for People on the Autism Spectrum.
Autistic self-advocates, family members, and community organizations have called for greater emphasis on enhancing quality of life (QoL) for people with autism. Doing this is critical to understand how QoL unfolds across the life course and to clarify whether gender affects QoL, health, and functioning for people with autism. The purpose of this study was to curate and test a lifespan QoL measurement tool using freely available and well-constructed National Institutes of Health Parent-Reported Outcomes Measurement Information System (PROMIS). To develop the PROMIS Autism Battery-Lifespan (PAB-L), we identified PROMIS scales relevant for autism, reviewed each item, consulted with a panel of autism experts, and elicited feedback from autistic people and family members. This battery provides a comprehensive portrait of QoL for children ages 5-13 (through parent proxy), teens 14-17 (parent proxy and self-report), and adults 18-65 (self-report) with autism compared to the general population. Participants and parent informants (N = 912) recruited through a children's hospital and nationwide U.S. autism research registry completed the PAB-L online. Results indicate that compared to general population norms, people with autism of all ages (or their proxies) reported less desirable outcomes and lower QoL across all domains. Women and girls experienced greater challenges in some areas compared to men and boys with autism. The PAB-L appears to be a feasible and acceptable method for assessing patient-reported outcomes and QoL for autistic people across the life course. Autism Res 2020, 13: 970-987. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We developed a survey to measure the quality of life of children, teens, and adults with autism using free National Institutes of Health PROMIS questionnaires. People with autism and family members rated the PROMIS Autism Battery-Lifespan as useful and important. Some reported a good quality of life, while many reported that their lives were not going as well as they wanted. Women and girls reported more challenges in some areas of life than men and boys.


[Spatial Variation of Ammonia-N, Nitrate-N and Nitrite-N in Groundwater of Dongshan Island].
In Dongshan Island, groundwater is the main resource of the local residents' drinking water, domestic water, agriculture irrigation and freshwater aquaculture. This study aimed to investigate the spatial distribution characteristic and its variation pattern of ammonia-N, nitrate-N and nitrite-N in groundwater, as well as its pollution source and influence factors. It is very important to understand the pollution level of ammonia-N, nitrate-N and nitrite-N in groundwater of Dongshan Island, the control and prevention of ammonia-N, nitrate-N and nitrite-N pollution, which is of great significance to the residents' health. In this study, the spatial variability characteristics of ammonia-N, nitrate-N and nitrite-N concentration in groundwater of Dongshan Island was analysed by geo- statistic method, the values of the non-observation points were determined by Kriging method, and the pollution characteristics of ammonia-N, nitrate-N and nitrite-N in groundwater of Dongshan Island was also analyzed. Our results showed that the ammonia-N and nitrite-N concentration in groundwater of Dongshan Island were at low levels, but their spatial variability were high, and their autocorrelation were poor; however, the nitrate-N concentration was general high, its spatial variability was moderate, and the autocorrelation was much good. The distribution characteristics of ammonia-N, nitrate-N and nitrite-N in groundwater of Dongshan Island were similar that the high concentration areas were all located in the coastal land. The domestic pollutants and human and animal wastes from towns and villages were the main sources of nitrogen pollution, which would be the first step to control the nitrogen pollution of Dongshan Island. Land use pattern, soil type, groundwater depth, pH, dissolved oxygen, season, and the existence of Fe2+, were the impact factors that influence the distribution and transformation of ammonia-N, nitrate-N and nitrite-N in groundwater, which could be the considerable factors in the control of nitrogen pollution in groundwater of Dongshan Island.


Tanning of grasshopper eggs by an exocrine secretion.
Eggs of the grasshopper, Romalea microptera, are laid in a tightcluster, encased within a matrix of hardened froth. When first laid, the eggs are yellow and soft, and the froth is white and lathery. During subsequent hours, eggs and froth undergo a tanning process, as a result of which they harden and darken. An exocrine secretion, supplied by a pair of glands situated beside the gonopore, is mixed with the froth as the eggs are laid, and serves to promote tanning. Similar glands are found in some, but not all grasshoppers.


The spatial orientation of Helicobacter pylori in the gastric mucus.
The highly motile human pathogen Helicobacter pylori lives deep in the gastric mucus layer. To identify which chemical gradient guides the bacteria within the mucus layer, combinations of luminal perfusion, dialysis, and ventilation were used to modify or invert transmucus gradients in anaesthetized Helicobacter-infected mice and Mongolian gerbils. Neither changes in lumen or arterial pH nor inversion of bicarbonate/CO2 or urea/ammonium gradients disturbed Helicobacter orientation. However, elimination of the mucus pH gradient by simultaneous reduction of arterial pH and bicarbonate concentration perturbed orientation, causing the bacteria to spread over the entire mucus layer. H. pylori thus uses the gastric mucus pH gradient for chemotactic orientation.


[Immunological studies in 2 species of Ceratophrys (Anura Leptodactylidae): C. ornata (Bell, 1843) and C. cranwelli (Barrio, 1979)].
Two related species of the genus Ceratophrys (C. ornata and C. cranwelli) were studied by immunological techniques in order to find non-morphological characters which would allow to classify them more precisely. Bidimensional immunodiffusion of serum proteins showed extensive crossreactivity between both species, thus revealing their close relatíonship. However, by immunoelectrophoretic techniques, differences between their serum fractions were detected. The antisera raised in rabbits against the serum proteins showed different potency in reacting with the sera of each species. Sharper precipitation bands were obtained with the homologous serum. Two lipoproteic fractions, in the serum of both species, were also characterized.


Detection of tongue cancer in primary care.
The incidence of tongue cancer is increasing, and survival has not improved since the majority of patients present at an advanced stage. Patient delay has remained the same over the years and is difficult to influence. Much less is known about the delay in diagnosis caused by physicians and dentists. To investigate the detection of tongue cancer in primary care in Northern Finland and to examine the consultation prevalence of oral symptoms in primary care in Finland. Analysis of data from medical records of tongue cancer patients kept between 1 January 1974 and 31 December 1994 for the general health insurance scheme. The two northernmost provinces of Finland (population of 700,000). Data were collected on demographic and clinical variables and on the first medical visit on 75 tongue cancer patients. In addition, primary care physicians recorded all patient visits during four weeks in 25 health centres randomly selected throughout Finland in 1996. At the initial visit, the tongue cancer patient was correctly referred for further examinations in 49 (65%) cases. In 12 (16%) of cases the patient was not referred but was scheduled for a follow-up visit, and was neither referred nor followed-up in 14 (19%). When compared with the referred patients the median professional delay was somewhat longer for the unreferred patients but increased dramatically if no follow-up was arranged (0.6 months [range = 0.1-2.4] versus 1.2 [range = 0.3-2.2] versus 5.2 [range = 0.7-18.2], P < 0.001). Compared with the referred patients the adjusted relative hazard of death for the non-referred followed-up patients was 1.4 (95% confidence interval [CI] = 0.31-6.5) and that for the non-referred/not followed-up patients 6.3 (95% CI = 1.7-22.9). The high-risk patients included those who sought an early professional evaluation, those who made the appointment for a completely different reason and only mentioned the symptom suggestive of cancer incidentally, those that had a small ulcerative lesion, and blue-collar workers. Oral symptoms were a rare cause of visits (0.55% of all visits) in primary care in Finland. Misdiagnosis of tongue cancer at the initial professional evaluation often leads to a fatal delay if the patient is left without any follow-up.


Radiotherapy and Male Breast Cancer: A Population-based Registry Analysis.
The local-regional management of female breast cancer has been extensively investigated worldwide. The optimal approach for males diagnosed with breast cancer is less clear. We have analyzed the treatment of male breast cancer using a population-based national registry to determine the impact of surgery and radiation therapy on survival. The Surveillance Epidemiology and End Results (SEER) database was queried to identify males with invasive ductal carcinoma of the breast who underwent primary surgical resection (radical mastectomy, modified radical mastectomy, total mastectomy, or segmental) for the years 1983 to 2002. Demographic, clinical, and pathologic data were culled and analyzed to determine the impact of radiation therapy (RT) following resection. Survival rates were estimated using the Kaplan-Meier method and significance was determined using the log-rank test (P<0.05). Multivariate analysis with the Cox proportional hazards model was performed to determine factors significant for overall (OS) and cause-specific survival (CSS). A total of 1337 patients met the eligibility criteria and were analyzed. Median follow-up was 7.3 years (range, 1 mo to 25 y). Most men underwent modified radical mastectomy (n=1062) with a minority undergoing segmental (n=113). About 329 men received postoperative external beam RT. The median rates of OS and CSS for all men were 10.5 years and not yet reached, respectively. The surgical procedure did not significantly associate with OS or CSS. By stage, RT was associated with improved OS for stage I (P=0.03). There was a trend for improved survival with stage II (P=0.21) and III (P=0.15). RT was not associated with improved CSS by stage. RT improved rates of OS and CSS in N2 patients without reaching statistical significance (P=0.10 and 0.22). On multivariate analysis, advancing age, stage and grade, and no postoperative RT predicted for worse OS. However, when controlled for those with known hormone receptor status (n=978), only the factors of advancing age, stage, grade, and hormone receptor negativity predicted for worse OS. Advancing age, stage, and grade were the only predictors of CSS irrespective of the cohort analyzed. The primary surgical procedure did not ultimately influence OS or CSS in this population-based registry of males with breast cancer. A statistically nonsignificant improvement with postoperative RT was observed in men with lymph node involvement, larger tumor size, or higher stage. When controlled for age, stage, and grade in multivariate analysis, postoperative RT predicted for improved OS but not CSS. These data suggest a beneficial effect of RT in the postoperative setting. A prospective study is necessary to further elucidate appropriate treatment strategies for men with breast cancer.


Diagnosis of medial knee pain: atypical stress fracture about the knee joint.
Resident's case problem. A 19-year-old female, currently enrolled in a military training program, sought medical care for a twisting injury to her right knee. The patient reported her symptoms as similar to an injury she incurred 1 year previously while enrolled in the same military program. The patient's past medical history included a nondepressed fracture of the medial tibial plateau and complete tear of the deep fibers of the medial collateral ligament. Physical exam revealed nonlocalized anterior and medial knee pain without evidence of internal derangement. Initial knee and tibia radiographs were unremarkable. Referral for orthopedic physician evaluation resulted in concurrence with the therapist's diagnosis and plan of care, and the patient was allowed to continue with limited physical training demands. Despite periods of rest, the patient's symptoms progressively worsened upon attempts to resume running. The examining therapist referred the patient for magnetic resonance imaging (MRI) due to the patient's worsening symptoms, normal radiographs, and concern for a proximal tibia stress fracture. MRI revealed a severe proximal tibial metaphysis stress fracture. Stress fractures are commonly encountered injuries in individuals subjected to increased physical training demands. Early evaluation may not yield well-localized findings and may mimic other conditions. Nonmusculoskeletal conditions should be considered in the management of patients with stress fractures. This resident's case problem illustrates the importance of serial physical examinations and collaboration with other healthcare practitioners in the comprehensive assessment and management of a patient with a severe stress fracture.


Adeno-associated virus vector-mediated transgene integration into neurons and other nondividing cell targets.
The site-specific integration of wild-type adeno-associated virus (wtAAV) into the human genome is a very attractive feature for the development of AAV-based gene therapy vectors. However, knowledge about integration of wtAAV, as well as currently configured recombinant AAV (rAAV) vectors, is limited. By using a modified Alu-PCR technique to amplify and sequence the vector-cellular junctions, we provide the first direct evidence both in vitro and in vivo of rAAV-mediated transgene integration in several types of nondividing cells, including neurons. This novel technique will be highly useful for further delineating the mechanisms underlying AAV-mediated integration, including issues of frequency, site preference, and DNA rearrangement in human as well as animal cells. Results from these studies should be beneficial for the development of the next generation of gene delivery vectors.


The epithelial origin of a stromal cell population in adenocarcinoma of the rat prostate.
Dunning R3327-H rat prostate adenocarcinoma cells, when grown in syngeneic (Copenhagen) rats or nude mice, produce tumors with prominent hypercellular stroma. The authors have previously demonstrated the presence of anomalous steroid-sensitive cells in both the epithelium and stromal compartments of this model system. In order to better understand the histogenesis of these cells, the authors studied samples of the tumor which were radiolabeled overnight with tritiated dihydrotestosterone (3H-DHT). Frozen sections of the tissues were thaw-mounted onto autoradiographic emulsion-coated slides to permit silver grain identification in association with nuclei of androgen-sensitive cells. Surprisingly, numerous silver grains were found to be associated with nuclei of large cells within the stroma. Therefore, these cells were termed "epithelioid" pending confirmation of their origin. To further define these cells and their relationship to the surrounding matrix, autoradiograms have now been examined immunohistochemically with antibodies directed against the basement membrane glycoprotein, laminin, as well as antibodies specific for intermediate cytoskeletal filaments. Following identification of acinar basement membranes, epithelioid cells were identifiable both in the stroma and in the acinar epithelial cell layer. Histochemical staining with acid phosphatase, a marker for prostatic epithelium, was performed and shown to be present in acinar epithelial cells as well as in epithelioid cells. Additionally, fluorescence-activated cell sorting was employed to characterize the DNA content of cell types within the H tumor. Epithelioid cells were found to be in highest concentration in an aneuploid peak with a ploidy of approximately 6N. The autoradiographic, immunohistochemical, cytometric, and ultramicroscopic studies suggest that 1) epithelioid cells are epithelial derived stromal cells; 2) these epithelioid cells arise by pathologic division of aneuploid neoplastic precursor cells of approximately 3N ploidy, which are found within the prostatic epithelium; and 3) the resulting 6N cells degrade the basement membrane locally, invade the stroma, and populate it. Here, they can be distinguished from fibroblasts by their size, acid phosphatase activity, and hormone receptor content. Thus, the term "epithelioid" is inappropriate; and these cells should be regarded simply as large neoplastic epithelial (LNE) cells. The presence of this cell type suggests that this tumor subline represents a useful naturally occurring model for the study of the initial stages of neoplastic transformation.


Alcohol dehydrogenase-1B represses the proliferation, invasion and migration of breast cancer cells by inactivating the mitogen-activated protein kinase signalling pathway.
Breast cancer (BRCA) is a serious life-threatening cancer, especially triple-negative breast cancer (TNBC). Alcohol dehydrogenase-1B (ADH1B) has recently been revealed to be associated with poor prognosis of BRCA patients. This study identified the exact function of ADH1B on the progression of BRCA and TNBC. ADH1B effect on the prognosis of BRCA and TNBC patients was researched based on online databases and clinical samples. The function of ADH1B on the proliferation, invasion and migration, and growth of BRCA and TNBC cells was investigated by cell counting kit-8, Transwell, and in vivo assays. Western blot was utilized to determine the effect of ADH1B on the mitogen-activated protein kinase (MAPK) signalling pathway activity. As a result, ADH1B was down-regulated in BRCA and TNBC patients and cells, predicting unfavorable prognosis (P<0.05). ADH1B overexpression suppressed the proliferation, invasion and migration, and inactivated the MAPK signalling pathway in BRCA and TNBC cells (P<0.01). ADH1B synergized with Selumetinib (inhibitor of the MAPK signalling pathway) to attenuate the proliferation, invasion and migration of BRCA and TNBC cells (P<0.001). Conversely, Vacquinol-1 (activator of the MAPK signalling pathway) abolished the suppression of ADH1B on the proliferation, invasion and migration of BRCA and TNBC cells (P<0.05). ADH1B suppressed in vivo growth of TNBC cells (P<0.001). Thus, ADH1B may inhibit the proliferation, invasion and migration of BRCA and TNBC cells by inactivating the MAPK signalling pathway. It may be a promising target for the clinical treatment of BRCA and TNBC.


[Clinical practice guidelines. Diagnosis and treatment of diabetic retinopathy].
to develop a guideline available to the staff of the second and third level of medical care, that includes recommendations based on the best available evidence about diagnosis and management of diabetic retinopathy (DR). clinical questions were formulated and structured. A standardized sequence was established to search for practice guidelines from the clinical questions raised on diagnosis and treatment of DR. The working group searched clinical practice guidelines and found eleven on this topic. For recommendations not included in the reference guide, the search process was conducted in PubMed and Cochrane Library. The results were expressed as levels of evidence and grade of recommendation. in Mexico diabetic retinopathy is a main cause of blindness in the active working population. It is necessary to establish a program for detection of at-risk population that allow make early diagnosis and opportune management for reducing blindness in patients. It is equally important to be aware of the need for long-term good metabolic control, which is associated with better quality of life.


A DNA nanoscope via auto-cycling proximity recording.
Analysis of the spatial arrangement of molecular features enables the engineering of synthetic nanostructures and the understanding of natural ones. The ability to acquire a comprehensive set of pairwise proximities between components would satisfy an increasing interest in investigating individual macromolecules and their interactions, but current biochemical techniques detect only a single proximity partner per probe. Here, we present a biochemical DNA nanoscopy method that records nanostructure features in situ and in detail for later readout. Based on a conceptually novel auto-cycling proximity recording (APR) mechanism, it continuously and repeatedly produces proximity records of any nearby pairs of DNA-barcoded probes, at physiological temperature, without altering the probes themselves. We demonstrate the production of dozens of records per probe, decode the spatial arrangements of 7 unique probes in a homogeneous sample, and repeatedly sample the same probes in different states.The spatial organisation of nanostructures is fundamental to their function. Here, the authors develop a non-destructive, proximity-based method to record extensive spatial organization information in DNA molecules for later readout.


HHMMiR: efficient de novo prediction of microRNAs using hierarchical hidden Markov models.
MicroRNAs (miRNAs) are small non-coding single-stranded RNAs (20-23 nts) that are known to act as post-transcriptional and translational regulators of gene expression. Although, they were initially overlooked, their role in many important biological processes, such as development, cell differentiation, and cancer has been established in recent times. In spite of their biological significance, the identification of miRNA genes in newly sequenced organisms is still based, to a large degree, on extensive use of evolutionary conservation, which is not always available. We have developed HHMMiR, a novel approach for de novo miRNA hairpin prediction in the absence of evolutionary conservation. Our method implements a Hierarchical Hidden Markov Model (HHMM) that utilizes region-based structural as well as sequence information of miRNA precursors. We first established a template for the structure of a typical miRNA hairpin by summarizing data from publicly available databases. We then used this template to develop the HHMM topology. Our algorithm achieved average sensitivity of 84% and specificity of 88%, on 10-fold cross-validation of human miRNA precursor data. We also show that this model, trained on human sequences, works well on hairpins from other vertebrate as well as invertebrate species. Furthermore, the human trained model was able to correctly classify ~97% of plant miRNA precursors. The success of this approach in such a diverse set of species indicates that sequence conservation is not necessary for miRNA prediction. This may lead to efficient prediction of miRNA genes in virtually any organism.


[Incidence of amantadine-resistant influenza A (genotype Ser-31-Asn) in nursing homes in Niigata, Japan].
The antiviral agent amantadine specifically inhibit influenza A virus infection, but the emergence of drug-resistant viruses occur more readily with amantadine treatment. In human influenza viruses, single amino acid changes at 4 sites spanning the transmembrane domain of the M2 protein can confer drug resistance. Amantadine was approved for treatment of Parkinson's disease in 1975, and for the influenza A virus infection in November 1998, in Japan. Annual consumption of amantadine for influenza treatment increased suddenly after the approval. According to our previous report, the predominant genotype of resistant virus is the substitution S-31-N in M2 both in vitro and in clinical samples, as in the other reports. Based on the above findings, we focused on single amino acid change at position 31 (genotype S-31-N) and applied polymerase chain-reaction restriction fragment length polymorphism (PCR-RFLP), directly from throat swab samples, by using primers that insert a restriction site for Sca I. With this technique, we surveyed the incidence of amantadine resistant viruses in nursing homes, Niigata, Japan. Thirty-one (22.0%) of 141 PCR positive samples from 8 nursing homes in 1998-99 season showed resistant patterns, and only 6 (19.4%) of them were after the administration of amantadine for treatment. All of these 8 nursing homes used amantadine for Parkinson's disease, but only half of them used the drug for influenza A infection. The incidence of resistant viruses was not significantly different from facilities with amantadine for influenza treatment to those without, 25.5% and 14.0% respectively. The occurrence of outbreaks and sporadic illness in those facilities, with different administration status were observed, but fortunately we could not find any evidence to relate the emergence of resistant viruses to the outbreaks. This is the first report that the resistant influenza viruses already exist in nursing facilities where amantadine was used for not only influenza but also Parkinson's disease in Japan.


Automatic extraction of biological information from scientific text: protein-protein interactions.
We describe the basic design of a system for automatic detection of protein-protein interactions extracted from scientific abstracts. By restricting the problem domain and imposing a number of strong assumptions which include pre-specified protein names and a limited set of verbs that represent actions, we show that it is possible to perform accurate information extraction. The performance of the system is evaluated with different cases of real-world interaction networks, including the Drosophila cell cycle control. The results obtained computationally are in good agreement with current biological knowledge and demonstrate the feasibility of developing a fully automated system able to describe networks of protein interactions with sufficient accuracy.


Molecular modelling and enzymatic studies of acetylcholinesterase and butyrylcholinesterase recognition with paraquat and related compounds.
The potent herbicide paraquat and three other analogues MPP+, MPDP+ and MPTP have a known toxicological profile linked to the ability to damage dopaminergic neurons. Other biological effects were recently addressed to this class of compounds, including the ability to interact with enzymatic targets involved in the Central Nervous System, such as the acetylcholinesterase (AChE) and the butyrylcholinesterase (BuChE). A combined molecular modelling and enzymatic study focusing onto their interaction against the AChE and BuChE is reported. The former study was performed by docking techniques using target known co-crystallographic models. The latter study was carried out by the widely adopted Ellman's method. In both studies the anti-Alzheimer FDA approved drug tacrine was used as reference inhibitor. Our results indicate that paraquat, MPTP, MPDP+ and MPP+ recognize both enzymatic cleft in a similar fashion compared to the reference inhibitor. A structure-activity correlation was found with the net charge of the ligands, indicating a major role of the electrostatic term in the recognition and inhibition of these compounds. Our data completed their enzymatic profile, added new information on the molecular mechanisms underlying their neurotoxicity useful for the rational design of new cholinesterase inhibitors.


Impact of commercial housing systems and nutrient and energy intake on laying hen performance and egg quality parameters.
The US egg industry is exploring alternative housing systems for laying hens. However, limited published research related to cage-free aviary systems and enriched colony cages exists related to production, egg quality, and hen nutrition. The laying hen's nutritional requirements and resulting productivity are well established with the conventional cage system, but diminutive research is available in regards to alternative housing systems. The restrictions exist with limited availability of alternative housing systems in research settings and the considerable expense for increased bird numbers in a replicate due to alternative housing system design. Therefore, the objective of the current study was to evaluate the impact of nutrient and energy intake on production and egg quality parameters from laying hens housed at a commercial facility. Lohmann LSL laying hens were housed in three systems: enriched colony cage, cage-free aviary, and conventional cage at a single commercial facility. Daily production records were collected along with dietary changes during 15 production periods (28-d each). Eggs were analyzed for shell strength, shell thickness, Haugh unit, vitelline membrane properties, and egg solids each period. An analysis of covariance (ANCOVA) coupled with a principal components analysis (PCA) approach was utilized to assess the impact of nutritional changes on production parameters and monitored egg quality factors. The traits of hen-day production and mortality had a response only in the PCA 2 direction. This finds that as house temperature and Met intake increases, there is an inflection point at which hen-day egg production is negatively effected. Dietary changes more directly influenced shell parameters, vitelline membrane parameters, and egg total solids as opposed to laying hen housing system. Therefore, further research needs to be conducted in controlled research settings on laying hen nutrient and energy intake in the alternative housing systems and resulting impact on egg quality measures.


Paw preference in rats.
We applied a food-reaching test to investigate paw preference in 114 Spraque-Dawley rats and to determine whether a correlation exists between paw preference and gender. We found that 70.2% of rats were right-pawed, 19.3% were left-pawed, and 11.9% were ambidextrous. No significant difference was found between right-pawed, left-pawed, and ambidextrous male and female rats. The results indicate that the distribution of paw preference in rats is similar to that of other animals and to human handedness.


Epileptic negative myoclonus in herpes simplex virus encephalitis.
Epileptic negative myoclonus (ENM) is a rarely reported clinical seizure semiology. It is defined as a brief interruption of tonic muscle activity in association with an epileptiform discharge on the EEG (spike or sharp wave) without preceding myoclonia. The diagnosis of ENM requires a polygraphic recording with EEG and surface EMG electrodes covering the affected body part(s), while the muscles have tonic activity. Historically, ENM has been reported in a variety of chronic epilepsy syndromes such as benign epilepsy with centrotemporal spikes, progressive myoclonic epilepsy syndromes, symptomatic partial epilepsy syndromes due to structural pathologies, cryptogenic epilepsies, etc. In this paper, we report a patient with herpes simplex virus encephalitis who presented with multiple different seizure types including ENM. The patient showed significant improvement after treatment with acyclovir.


HT-eQTL: integrative expression quantitative trait loci analysis in a large number of human tissues.
Expression quantitative trait loci (eQTL) analysis identifies genetic markers associated with the expression of a gene. Most existing eQTL analyses and methods investigate association in a single, readily available tissue, such as blood. Joint analysis of eQTL in multiple tissues has the potential to improve, and expand the scope of, single-tissue analyses. Large-scale collaborative efforts such as the Genotype-Tissue Expression (GTEx) program are currently generating high quality data in a large number of tissues. However, computational constraints limit genome-wide multi-tissue eQTL analysis. We develop an integrative method under a hierarchical Bayesian framework for eQTL analysis in a large number of tissues. The model fitting procedure is highly scalable, and the computing time is a polynomial function of the number of tissues. Multi-tissue eQTLs are identified through a local false discovery rate approach, which rigorously controls the false discovery rate. Using simulation and GTEx real data studies, we show that the proposed method has superior performance to existing methods in terms of computing time and the power of eQTL discovery. We provide a scalable method for eQTL analysis in a large number of tissues. The method enables the identification of eQTL with different configurations and facilitates the characterization of tissue specificity.


"Fitspiration" on Social Media: A Content Analysis of Gendered Images.
"Fitspiration" (also known as "fitspo") aims to inspire individuals to exercise and be healthy, but emerging research indicates exposure can negatively impact female body image. Fitspiration is frequently accessed on social media; however, it is currently unclear the degree to which messages about body image and exercise differ by gender of the subject. The aim of our study was to conduct a content analysis to identify the characteristics of fitspiration content posted across social media and whether this differs according to subject gender. Content tagged with #fitspo across Instagram, Facebook, Twitter, and Tumblr was extracted over a composite 30-minute period. All posts were analyzed by 2 independent coders according to a codebook. Of the 415/476 (87.2%) relevant posts extracted, most posts were on Instagram (360/415, 86.8%). Most posts (308/415, 74.2%) related thematically to exercise, and 81/415 (19.6%) related thematically to food. In total, 151 (36.4%) posts depicted only female subjects and 114/415 (27.5%) depicted only male subjects. Female subjects were typically thin but toned; male subjects were often muscular or hypermuscular. Within the images, female subjects were significantly more likely to be aged under 25 years (P<.001) than the male subjects, to have their full body visible (P=.001), and to have their buttocks emphasized (P<.001). Male subjects were more likely to have their face visible in the post (P=.005) than the female subjects. Female subjects were more likely to be sexualized than the male subjects (P=.002). Female #fitspo subjects typically adhered to the thin or athletic ideal, and male subjects typically adhered to the muscular ideal. Future research and interventional efforts should consider the potential objectifying messages in fitspiration, as it relates to both female and male body image.


Manipulating Cellular Activities Using an Ultrasound-Chemical Hybrid Tool.
We developed an ultrasound-chemical hybrid tool to precisely manipulate cellular activities. A focused ultrasound coupled with gas-filled microbubbles was used to rapidly trigger the influx of membrane-impermeable chemical dimerizers into living cells to regulate protein dimerization and location without inducing noticeable toxicity. With this system, we demonstrated the successful modulation of phospholipid metabolism triggered by a short pulse of ultrasound exposure. Our technique offers a powerful and versatile tool for using ultrasound to spatiotemporally manipulate the cellular physiology in living cells.


Oxidative Stress and Marine Carotenoids: Application by Using Nanoformulations.
Carotenoids are natural fat-soluble pigments synthesized by plants, algae, fungi and microorganisms. They are responsible for the coloration of different photosynthetic organisms. Although they play a role in photosynthesis, they are also present in non-photosynthetic plant tissues, fungi, and bacteria. These metabolites have mainly been used in food, cosmetics, and the pharmaceutical industry. In addition to their utilization as pigmentation, they have significant therapeutically applications, such as improving immune system and preventing neurodegenerative diseases. Primarily, they have attracted attention due to their antioxidant activity. Several statistical investigations indicated an association between the use of carotenoids in diets and a decreased incidence of cancer types, suggesting the antioxidant properties of these compounds as an important factor in the scope of the studies against oxidative stress. Unusual marine environments are associated with a great chemical diversity, resulting in novel bioactive molecules. Thus, marine organisms may represent an important source of novel biologically active substances for the development of therapeutics. Marine carotenoids (astaxanthin, fucoxanthin, β-carotene, lutein but also the rare siphonaxanthin, sioxanthin, and myxol) have recently shown antioxidant properties in reducing oxidative stress markers. Numerous of bioactive compounds such as marine carotenoids have low stability, are poorly absorbed, and own very limited bioavailability. The new technique is nanoencapsulation, which can be used to preserve marine carotenoids and their original properties during processing, storage, improve their physiochemical properties and increase their health-promoting effects. This review aims to describe the role of marine carotenoids, their potential applications and different types of advanced nanoformulations preventing and treating oxidative stress related disorders.


Long-term femoral bone remodeling after cemented hip arthroplasty with the Müller straight stem in the operated and nonoperated femora.
We investigated the cortical bone changes in 35 patients with total hip arthroplasty operated on only for osteoarthritis with more than 10 years of follow-up and with nonrevised femoral components and without radiologic signs of loosening. The mean follow-up was 16 ± 5 years. The thicknesses of femoral cortices were measured medially and laterally at 6 levels from the first postoperative and the last follow-up x-rays. A comparison with 10 patients who had a nonoperated contralateral hip was performed. We found a significant decrease in cortical thicknesses in total hip arthroplasty. The cortical thinning was significant at all periprosthetic levels but less expressed distally. Prosthetic femora were associated with greater cortical thinning as compared with the contralateral nonoperated femora, exceeding that caused by natural aging.


North or south? Phylogenetic and biogeographic origins of a globally distributed avian clade.
Establishing phylogenetic relationships within a clade can help to infer ancestral origins and indicate how widespread species reached their current biogeographic distributions. The small plovers, genus Charadrius, are cosmopolitan shorebirds, distributed across all continents except Antarctica. Here we present a global, species-level molecular phylogeny of this group based on four nuclear (ADH5, FIB7, MYO2 and RAG1) and two mitochondrial (COI and ND3) genes, and use the phylogeny to examine the biogeographic origin of the genus. A Bayesian multispecies coalescent approach identified two major clades (CRD I and CRD II) within the genus. Clade CRD I contains three species (Thinornis novaeseelandiae, Thinornis rubricollis and Eudromias morinellus), and CRD II one species (Anarhynchus frontalis), that were previously placed outside the Charadrius genus. In contrast to earlier work, ancestral area analyses using parsimony and Bayesian methods supported an origin of the Charadrius plovers in the Northern hemisphere. We propose that major radiations in this group were associated with shifts in the range of these ancestral plover species, leading to colonisation of the Southern hemisphere.


It is time to remove the 'benign' from the essential tremor label.
In recent years, studies of essential tremor (ET) have demonstrated that the disease is associated with functionally-relevant cognitive abnormalities, a mood disturbance and other psychiatric co-morbidities, a functionally significant gait disorder, hearing deficits, and a variety of types of tremor. The tremor has been shown to be progressive in nature and quite disabling for a large number of sufferers. Also, recent clinical-epidemiological studies have linked prevalent ET to other neurodegenerative diseases and at least one study has demonstrated an increased risk of mortality in an ET cohort. While many of these studies are derived from clinic-based samples, population-based studies have also substantiated these findings, suggesting that even in the general population, the disease is associated with disability and with co-morbidity. Based on these available studies, it would seem inaccurate to append the word "benign" to ET. Not unlike the word "essential" itself, the word "benign" is an antiquated and outdated term that reflects an era where little was understood about ET. Historically, the general doctors who frequently encountered the disorder would educate patients that it was a benign, non-progressive condition not associated with any co-morbidity or risk of long-term worry. This notion, conceived by prior generations of physicians, is now known to be inaccurate. It is therefore our recommendation that the medical community open the dialog to consider formally discontinuing this nosology ("benign essential tremor") and to adopt the use of the term "essential tremor." Use of the word "benign" is a mischaracterization of the disease course, and could be prove misleading especially in the evolving doctor-patient relationship. In those cases with currently-mild tremor, the nosology "mild essential tremor" would be a more accurate reflection of disease.


Chronic consumption of a high linoleic acid diet during pregnancy, lactation and post-weaning period increases depression-like behavior in male, but not female offspring.
Polyunsaturated fatty acids (PUFAs) play an essential role in brain development. Emerging data have suggested a possible link between an imbalance in PUFAs and cognitive behavioral deficits in offspring. A diet rich in high linoleic acid (HLA), typically from preconception to lactation, leads to an increase in the ratio of omega-6 (n-6) to omega-3 (n-3) fatty acids in the fetus. Arising research has suggested that a deficiency in omega-3 fatty acids is a potential risk factor for inducing autism spectrum disorder (ASD)-like behavioral deficits. However, the impact of a high n- diet during preconception, pregnancy, lactation, and post-weaning on the brain development of adolescent offspring are yet to be determined. This study examined whether consumption of an HLA diet during pregnancy, lactation, and post-weaning induced social and cognitive impairments in female and male offspring rats that resemble autistic phenotypes in humans. Female Wistar Kyoto rats were fed with either HLA or low linoleic acid (LLA) control diet for 10 weeks before mating, then continued with the same diet throughout the pregnancy and lactation period. Female and male offspring at 5 weeks old were subjected to behavioral tests to assess social interaction behavior and depression-/anxiety-like behavior. Our result showed that chronic consumption of an HLA diet did not affect sociability and social recognition memory, but induced depression-like behavior in male but not in female offspring.


Characterisation of the physical composition and microbial community structure of biofilms within a model full-scale drinking water distribution system.
Within drinking water distribution systems (DWDS), microorganisms form multi-species biofilms on internal pipe surfaces. A matrix of extracellular polymeric substances (EPS) is produced by the attached community and provides structure and stability for the biofilm. If the EPS adhesive strength deteriorates or is overcome by external shear forces, biofilm is mobilised into the water potentially leading to degradation of water quality. However, little is known about the EPS within DWDS biofilms or how this is influenced by community composition or environmental parameters, because of the complications in obtaining biofilm samples and the difficulties in analysing EPS. Additionally, although biofilms may contain various microbial groups, research commonly focuses solely upon bacteria. This research applies an EPS analysis method based upon fluorescent confocal laser scanning microscopy (CLSM) in combination with digital image analysis (DIA), to concurrently characterize cells and EPS (carbohydrates and proteins) within drinking water biofilms from a full-scale DWDS experimental pipe loop facility with representative hydraulic conditions. Application of the EPS analysis method, alongside DNA fingerprinting of bacterial, archaeal and fungal communities, was demonstrated for biofilms sampled from different positions around the pipeline, after 28 days growth within the DWDS experimental facility. The volume of EPS was 4.9 times greater than that of the cells within biofilms, with carbohydrates present as the dominant component. Additionally, the greatest proportion of EPS was located above that of the cells. Fungi and archaea were established as important components of the biofilm community, although bacteria were more diverse. Moreover, biofilms from different positions were similar with respect to community structure and the quantity, composition and three-dimensional distribution of cells and EPS, indicating that active colonisation of the pipe wall is an important driver in material accumulation within the DWDS.


Polymorphisms in the brain-derived neurotrophic factor gene influence memory and processing speed one month after brain injury.
Brain-derived neurotrophic factor (BDNF) plays a role in cognition, as well as neural survival and plasticity. There are several common polymorphisms in the BDNF gene, one of which (rs6265) is an extensively studied non-synonymous coding polymorphism (Val66Met) which has been linked to cognitive performance in healthy controls and some clinical populations. We hypothesized that the Met allele of rs6265 would be associated with poorer cognitive performance in individuals with mild-to-moderate traumatic brain injury, and that other polymorphisms in the BDNF gene would also affect cognition. Genotype at 9 single-nucleotide polymorphisms (SNPs) in the BDNF gene, and measures of speed of information processing, learning, and memory were assessed in 75 patients with mTBI and 38 healthy subjects. Consistent with previous reports, the Met allele of rs6265 was associated with cognition (slower processing speed) in the entire group. Two other SNPs were associated with processing speed in the mTBI group, but both are in linkage disequilibrium with rs6265, and neither remained significant after adjustment for rs6265 status. Within the mTBI group, but not the controls, 4 SNPs, but not rs6265, were associated with memory measures. These associations were not affected by adjustment for rs6265 status. Polymorphisms in BDNF influence cognitive performance shortly after mTBI. The results raise the possibility that a functional polymorphism other than rs6265 may contribute to memory function after mTBI.


Probiotics Streptococcus salivarius 24SMB and Streptococcus oralis 89a interfere with biofilm formation of pathogens of the upper respiratory tract.
Infections of the ears, paranasal sinuses, nose and throat are very common and represent a serious issue for the healthcare system. Bacterial biofilms have been linked to upper respiratory tract infections and antibiotic resistance, raising serious concerns regarding the therapeutic management of such infections. In this context, novel strategies able to fight biofilms may be therapeutically beneficial and offer a valid alternative to conventional antimicrobials. Biofilms consist of mixed microbial communities, which interact with other species in the surroundings and communicate through signaling molecules. These interactions may result in antagonistic effects, which can be exploited in the fight against infections in a sort of "bacteria therapy". Streptococcus salivarius and Streptococcus oralis are α-hemolytic streptococci isolated from the human pharynx of healthy individuals. Several studies on otitis-prone children demonstrated that their intranasal administration is safe and well tolerated and is able to reduce the risk of acute otitis media. The aim of this research is to assess S. salivarius 24SMB and S. oralis 89a for the ability to interfere with biofilm of typical upper respiratory tract pathogens. To investigate if soluble substances secreted by the two streptococci could inhibit biofilm development of the selected pathogenic strains, co-cultures were performed with the use of transwell inserts. Mixed-species biofilms were also produced, in order to evaluate if the inhibition of biofilm formation might require direct contact. Biofilm production was investigated by means of a spectrophotometric assay and by confocal laser scanning microscopy. We observed that S. salivarius 24SMB and S. oralis 89a are able to inhibit the biofilm formation capacity of selected pathogens and even to disperse their pre-formed biofilms. Diffusible molecules secreted by the two streptococci and lowered pH of the medium revealed to be implied in the mechanisms of anti-biofilm activity. S. salivarius 24SMB and S. oralis 89a possess desirable characteristics as probiotic for the treatment and prevention of infections of the upper airways. However, the nature of the inhibition appear to be multifactorial and additional studies are required to get further insights.


[Evaluation of Chromalbicans Agar for presumptive identification of Candida albicans].
The utility of Chromalbicans Agar (Biolife Italiana, Milano, Italy) was evaluated with 723 clinical isolates and type culture collection strains from different genera including Candida, Cryptococcus, Pichia, Rhodotorula, Saccharomyces, Trichosporon y Zygosaccharomyces. Presumptive identification was confirmed by germ tube test and carbohydrate assimilation on API-ATB ID 32C (bioMerieux, France). Growth on Chromalbicans Agar was very useful for the presumptive identification of C. albicans isolates, and sensitivity and specificity values were significantly high (>97%), since a very low number of isolates were found to be false negative or false positive.


Impaired genome maintenance suppresses the growth hormone--insulin-like growth factor 1 axis in mice with Cockayne syndrome.
Cockayne syndrome (CS) is a photosensitive, DNA repair disorder associated with progeria that is caused by a defect in the transcription-coupled repair subpathway of nucleotide excision repair (NER). Here, complete inactivation of NER in Csb(m/m)/Xpa(-/-) mutants causes a phenotype that reliably mimics the human progeroid CS syndrome. Newborn Csb(m/m)/Xpa(-/-) mice display attenuated growth, progressive neurological dysfunction, retinal degeneration, cachexia, kyphosis, and die before weaning. Mouse liver transcriptome analysis and several physiological endpoints revealed systemic suppression of the growth hormone/insulin-like growth factor 1 (GH/IGF1) somatotroph axis and oxidative metabolism, increased antioxidant responses, and hypoglycemia together with hepatic glycogen and fat accumulation. Broad genome-wide parallels between Csb(m/m)/Xpa(-/-) and naturally aged mouse liver transcriptomes suggested that these changes are intrinsic to natural ageing and the DNA repair-deficient mice. Importantly, wild-type mice exposed to a low dose of chronic genotoxic stress recapitulated this response, thereby pointing to a novel link between genome instability and the age-related decline of the somatotroph axis.


Rational basis for the use of sleeping pills.
The diagnosis and treatment of insomnia is a major clinical issue. This is because the complaint of insomnia is highly prevalent and because the various clinical and laboratory manifestations of insomnia are complex. In addition, insomnia involves both day and night. This paper attempts to provide a rational framework for the evaluation of insomnia and the use of sleeping pills. Insomnia is defined and described with special attention to differentiating the subjective complaint and the laboratory assessment of objective sleep parameters. Specific disorders causing or associated with sleep disturbance and the complaint of insomnia are described, and some data bearing on relative prevalence of specific disorders are presented. Consideration of sleeping pills involves the evaluation of hypnotic efficacy as a property of the medication on the one hand and the practical clinical application on the other. Properties of different hypnotics are reviewed, including factors that affect the use of hypnotics in clinical practice. It is concluded that the rational use of sleeping pills demands a systematic approach to the evaluation of the individual patient and a specific attempt to formulate individual treatment goals together with a knowledgeable consideration of the specific chemotherapeutic agent to be utilized.


Coronavirus nucleocapsid protein facilitates template switching and is required for efficient transcription.
Purified nucleocapsid protein (N protein) from transmissible gastroenteritis virus (TGEV) enhanced hammerhead ribozyme self-cleavage and favored nucleic acid annealing, properties that define RNA chaperones, as previously reported. Several TGEV N-protein deletion mutants were expressed in Escherichia coli and purified, and their RNA binding ability and RNA chaperone activity were evaluated. The smallest N-protein domain analyzed with RNA chaperone activity, facilitating DNA and RNA annealing, contained the central unstructured region (amino acids 117 to 268). Interestingly, N protein and its deletion mutants with RNA chaperone activity enhanced template switching in a retrovirus-derived heterologous system, reinforcing the concept that TGEV N protein is an RNA chaperone that could be involved in template switching. This result is in agreement with the observation that in vivo, N protein is not necessary for TGEV replication, but it is required for efficient transcription.


Highly versatile heteroditopic ligand scaffolds for accommodating group 8, 9 & 11 heterobimetallic complexes.
Two highly versatile xanthene scaffolds containing pairs of heteroditopic ligands were found to be capable of accommodating a range of transition metal ions, including Au(i), Ir(i), Ir(iii), Rh(i), and Ru(ii) to generate an array of heterobimetallic complexes. The metal complexes were fully characterised and proved to be stable in the solid and solution state, with no observed metal-metal scrambling. Heterobimetallic complexes containing the Rh(i)/Ir(i) combinations were tested as catalysts for the two-step dihydroalkoxylation reaction of alkynediols and sequential hydroamination/hydrosilylation reaction of alkynamines.


[Riboflavin operon in Bacillus subtilis contains additional promoters].
Using the methods of molecular cloning permitted to show that riboflavin operon of Bacillus subtilis contains four promoters. Three of them are functionally active in the Bacillus subtilis system. The main promoter of the operon with regulatory region was cloned in plasmid pPL603. Cells containing the constructed plasmid pGM32 are resistant to chloramphenicol. The level of resistance is regulated by concentration of riboflavin (the effector of operon). The following model of rib-operon has been proposed: (Formula: see text).


Dietary habits in a Greek sample of men and women: the ATTICA study.
Although there are several dietary guidelines accepted at the international and national level, there are indications that dietary habits in Greece have been changing, moving away from the traditional Mediterranean diet pattern. The aim of this work was to evaluate the dietary habits of a randomly selected sample from the general adult population, in Greece. The "ATTICA" study is a prospective health and nutrition survey. For the purpose of this study, 3,042 adults, from whom 1514 were men (48%) and 1,528 were women (52%), were selected from the greater Athens area during 2001 and 2002. The assessment of the dietary habits was carried out using a validated food frequency questionnaire. Dietary intakes of red meat and sweets were higher (p<0.005), and dietary intakes of fish, poultry, dairy products, vegetables, and cereals were lower (p<0.05) than the ones recommended by the Hellenic Ministry of Health. The results from the present study indicate a change in the dietary habits towards an unhealthier type of diet.


Another piece of the Zika puzzle: assessing the associated factors to microcephaly in a systematic review and meta-analysis.
Although it is known that Zika virus (ZIKV) infection during pregnancy may lead to microcephaly in the fetus, the prognostic factors associated with this tragic disorder remain unclear. We conducted a systematic review and meta-analysis to assess the prognostic factors associated with the incidence of microcephaly in congenital ZIKV infection. We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of print, Embase, Embase Classic, Web of Science, CINAHL, Cochrane CENTRAL, LILACS, and various thesis databases to identify human studies reporting microcephaly associated with congenital ZIKV infection. We requested primary data from the authors of the included studies to calculate summary estimates and conduct the meta-analysis of the most prevalent factors. We screened 4106 titles and abstracts, and identified 12 studies for inclusion in the systematic review. The assessment of ZIKV infection and the definition of microcephaly varied among studies. A total of 6154 newborns/fetuses were enrolled; of those, 1120 (18.20%) had a diagnostic of ZIKV infection, of which 509 (45.45%) were diagnosed with microcephaly. Nine studies addressed the link between congenital ZIKV infection and neurological findings in newborns/fetuses. Half of the studies provided primary data. Three out of 11 factors of interest seem to be prognostic factors of microcephaly: infant's sex - males compared to females: Relative Risk (RR) 1.30, 95% Confidence Interval (95% CI) 1.14 to 1.49; the stage of pregnancy when infection occurred - infection in the first trimester of pregnancy compared to infection at other stages of pregnancy: RR 1.41, 95% CI 1.09 to 1.82; and asymptomatic infection compared to symptomatic infection during pregnancy: RR 0.68; 95% CI 0.60 to 0.77. Our findings support the female-biased resistance hypothesis and reinforce the risk associated with the stage of pregnancy when ZIKV infection occurs. Continued surveillance of ZIKV infection during pregnancy is needed to identify additional factors that could contribute to developing microcephaly in affected fetuses. This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration no. CRD 42018088075.


[Effect of the enterotropic carcinogen 1,2-dimethylhydrazine on the level of biogenic amines in the hypothalamus of rats].
The hypothalamic levels of noradrenaline (NA), dophamine (DA), serotonine (5-HT), 5-hydroxyindolacetic acid (5-HIAA) were found to be decreased in male rats 24 hours after subcutaneous injection of 1,2-dimethylhydrazine (SDMH) in a dose of 21 mg/kg. During 3 to 12 hrs after the SDMH treatment the hypothalamic level of NA was decreased, whereas the 5-HT turnover became greater. The hypothalamic histamine level increased 30 min after the SDMH injection only. In the brain stem and the great hemispheres the biogenic amine level displayed no significant changes under the effect of SDMH. The endocrine-metabolic changes due to the selected SDMH effect on the hypothalamic biogenic amine level are supposed to be of great significance in the realization of the carcinogenic action of SDMH in rats.


Dopamine D2/3 receptor availability in alcohol use disorder and individuals at high risk: Towards a dimensional approach.
Alcohol use disorder (AUD) is the most common substance use disorder worldwide. Although dopamine-related findings were often observed in AUD, associated neurobiological mechanisms are still poorly understood. Therefore, in the present study, we investigate D2/3 receptor availability in healthy participants, participants at high risk (HR) to develop addiction (not diagnosed with AUD), and AUD patients in a detoxified stage, applying 18 F-fallypride positron emission tomography (18 F-PET). Specifically, D2/3 receptor availability was investigated in (1) 19 low-risk (LR) controls, (2) 19 HR participants, and (3) 20 AUD patients after alcohol detoxification. Quality and severity of addiction were assessed with clinical questionnaires and (neuro)psychological tests. PET data were corrected for age of participants and smoking status. In the dorsal striatum, we observed significant reductions of D2/3 receptor availability in AUD patients compared with LR participants. Further, receptor availability in HR participants was observed to be intermediate between LR and AUD groups (linearly decreasing). Still, in direct comparison, no group difference was observed between LR and HR groups or between HR and AUD groups. Further, the score of the Alcohol Dependence Scale (ADS) was inversely correlated with D2/3 receptor availability in the combined sample. Thus, in line with a dimensional approach, striatal D2/3 receptor availability showed a linear decrease from LR participants to HR participants to AUD patients, which was paralleled by clinical measures. Our study shows that a core neurobiological feature in AUD seems to be detectable in an early, subclinical state, allowing more individualized alcohol prevention programs in the future.


Potential roles of follicular dendritic cell-associated osteopontin in lymphoid follicle pathology and repair and in B cell regulation in HIV-1 and SIV infection.
Osteopontin is a multifunctional protein with known roles in bone remodeling, wound healing, and normal and pathological immune responses. We showed in microarray studies that osteopontin gene expression is increased in human immunodeficiency virus type 1 (HIV-1)-infected lymphatic tissues after treatment, and we undertook mapping experiments to study osteopontin's possible functions in this context. We discovered species-specific colocalization of osteopontin with the follicular dendritic cell (FDC) network in lymphatic tissues in HIV-1 and simian immunodeficiency virus infections, and we found that changes in FDC-associated osteopontin covary with changes in lymphoid follicles during acute and late stages of infection and in response to treatment. We propose that this localization normally facilitates antibody production and plays a role in B cell abnormalities in infection and in the reconstitution of lymphoid follicles with treatment and that mapping genes identified in microarray studies is a useful experimental approach to gaining a better understanding of function in the context of a particular tissue and disease.


The routine differential leukocyte count vs automated differential counts.
The clinical use of the proposed performance standards for differential leukocyte counts is determined by multiple factors. Their use must be considered according to the specific use of the differential count, the sources of variability in differential counting, the relation between specific use and sources of variability, the role of analytic errors in the detection of nonspecific changes, the use of qualitative vs quantitative data, the sensitivity and specificity of the routine eye count, the role of disease or specific cell prevalence in determination of predictive value, the effect on use of automated instruments for screening, and whether abnormal specimen flagging can be done. The routine eye-count differential method, as performed by a well-trained technologist or technician, seems to lack both sensitivity and specificity. Because of the magnitude of technique- and method-related and biologic sources of variability, the 100- or 200-cell eye-count differential method is not a good screening method for detection of hematologic illnesses, particularly those that are uncommon. The automated differential leukocyte instruments address many of the technique- and method-related errors and are thus able to equal or exceed the performance of the routine eye-count differential method.


Contrast-enhanced computed tomography in acute pancreatitis: does contrast medium worsen its course due to impaired microcirculation?
An early and accurate diagnosis of severe acute (necrotizing) pancreatitis is important to allow timely institution of therapy to limit the extra-pancreatic sequelae of this necrotizing process and to minimize the incidence of super-infection of the necrosis (i.e., progression to infected necrosis). Contrast-enhanced computed tomography (CECT) has become the cornerstone of diagnosis by confirming the clinical diagnosis of severe acute pancreatitis based on the various clinical scoring criteria. Moreover, CECT serves as an anatomic roadmap for guiding radiological and surgical interventions. However, still-controversial experimental studies in animals in the mid-1990s suggested that the use of intravenous radiographic contrast media early in the course of the disease might exacerbate the necrotizing process by further impairing the already compromised pancreatic microcirculation. A series of experimental and clinical studies followed that have both refuted and supported this claim; unfortunately, none is conclusive, and the topic remains, as yet, unresolved. Our objective was to review objectively the available literature found by a Medline search on this subject. Meta-analysis and review. Our conclusion, after analysis of these studies, is that there are no well-substantiated data that could resolve the controversy. However, several caveats will be offered.


Examination of patients with acute dizziness in a neurological department.
Acute dizziness may have a number of causes, including cerebrovascular stroke which can present as isolated acute vestibular syndrome. It is recommended that acute episodic dizziness be assessed using positioning tests, and acute persistent dizziness with a focus on the HINTS (Head Impulse, Nystagmus, Test of Skew) battery of tests, which can distinguish cerebrovascular stroke from vestibular neuritis. We wished to identify the prevalence, diagnostic spectrum and approach to acute dizziness in a neurological department. We undertook a retrospective review of the medical records of all patients with acute dizziness as the primary symptom who where admitted to the department of neurology at Sørlandet Hospital, Kristiansand in 2015. Of 2 231 patients admitted to the department of neurology in 2015, altogether 243 (11 %) had dizziness as the primary symptom. A total of 106 patients (44 %) were examined using HINTS in its entirety. A cranial CT was performed in 213 (88 %) and MRI in 91 (37 %), and these showed relevant pathology in 1 and 4 patients, respectively. Upon discharge, 122 patients (50 %) were given a non-specific symptom diagnosis, 59 (24 %) received the diagnosis vestibular neuritis, 41 (17 %) benign paroxysmal positional vertigo, and 5 (2 %) were diagnosed with cerebrovascular stroke. Four out of five cases of cerebrovascular stroke could be classified retrospectively as acute vestibular syndrome, whereof three had typical findings determined by the HINTS test. Acute dizziness is a frequent symptom in patients admitted to the department of neurology. Evidence-based diagnostic recommendations for the assessment of acute dizziness were not satisfactorily implemented in practice.


Transposable Element Exaptation into Regulatory Regions Is Rare, Influenced by Evolutionary Age, and Subject to Pleiotropic Constraints.
Transposable element (TE)-derived sequences make up approximately half of most mammalian genomes, and many TEs have been co-opted into gene regulatory elements. However, we lack a comprehensive tissue- and genome-wide understanding of how and when TEs gain regulatory activity in their hosts. We evaluated the prevalence of TE-derived DNA in enhancers and promoters across hundreds of human and mouse cell lines and primary tissues. Promoters are significantly depleted of TEs in all tissues compared with their overall prevalence in the genome (P < 0.001); enhancers are also depleted of TEs, though not as strongly as promoters. The degree of enhancer depletion also varies across contexts (1.5-3×), with reproductive and immune cells showing the highest levels of TE regulatory activity in humans. Overall, in spite of the regulatory potential of many TE sequences, they are significantly less active in gene regulation than expected from their prevalence. TE age is predictive of the likelihood of enhancer activity; TEs originating before the divergence of amniotes are 9.2 times more likely to have enhancer activity than TEs that integrated in great apes. Context-specific enhancers are more likely to be TE-derived than enhancers active in multiple tissues, and young TEs are more likely to overlap context-specific enhancers than old TEs (86% vs. 47%). Once TEs obtain enhancer activity in the host, they have similar functional dynamics to one another and non-TE-derived enhancers, likely driven by pleiotropic constraints. However, a few TE families, most notably endogenous retroviruses, have greater regulatory potential. Our observations suggest a model of regulatory co-option in which TE-derived sequences are initially repressed, after which a small fraction obtains context-specific enhancer activity, with further gains subject to pleiotropic constraints.


Statin or nonsteroidal anti-inflammatory drug use is associated with lower erythrocyte sedimentation rate in patients with giant cell arteritis.
Previous studies have found that nonsteroidal anti-inflammatory drugs (NSAIDs) and statins may impact erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) levels in patients. The current study was performed to determine if NSAID or statin use is associated with lower ESR and CRP in patients with biopsy-proven giant cell arteritis (GCA). A retrospective cross-sectional study was conducted that included 161 patients via chart review. Charts of patients with GCA seen at the University of Iowa Hospitals and Clinics from 1960 to 2008 were reviewed. Inclusion criteria were adequate medication records, serum ESR and/or CRP on record, no prior corticosteroid use, and biopsy-positive GCA. Exclusion criteria were the presence of diseases known to elevate ESR or CRP. Main outcome measures included ESR and CRP values measured while evaluating patients for GCA but prior to receiving treatment. Statin nonusers had an ESR of 85.0 mm per hour (interquartile range [IQR] = 60-110 mm per hour) and a CRP of 8.7 mg/dL (IQR = 2.7-16.2 mg/dL). Statin users had an ESR of 57.5 mm per hour (IQR = 35-85) and a CRP of 2.4 mg/dL (IQR = 0.8-15.9 mg/dL). Statin use was associated with a lower ESR (P = 0.005), while there was no significant association with a lower CRP (P = 0.127). NSAID nonusers had an ESR of 98.0 mm per hour (IQR = 64-116) and a CRP of 8.7 mg/dL (IQR = 2.1-16.2 mg/dL). NSAID users had an ESR of 75.0 mm per hour (IQR = 46-98.5 mm per hour) and CRP of 8.0 mg/dL (IQR. = 1.5-16.2 mg/dL). NSAID use was associated with a lower ESR (P = 0.004), but there was no significant association with a lower CRP (P = 0.522). Statin use and NSAID use were associated with a lower ESR; however, they were not associated with lower CRP values. Clinicians should be aware that statin or NSAID use is associated with lower ESR in patients with GCA, and this test may therefore have lower sensitivity and specificity for recognizing patients with GCA, and CRP may be a superior test to evaluate patients for GCA.


An implantable ENG detector with in-system velocity selective recording (VSR) capability.
Detection and classification of electroneurogram (ENG) signals in the peripheral nervous system can be achieved by velocity selective recording (VSR) using multi-electrode arrays. This paper describes an implantable VSR-based ENG recording system representing a significant development in the field since it is the first system of its type that can record naturally evoked ENG and be interfaced wirelessly using a low data rate transcutaneous link. The system consists of two CMOS ASICs one of which is placed close to the multi-electrode cuff array (MEC), whilst the other is mounted close to the wireless link. The digital ASIC provides the signal processing required to detect selectively ENG signals based on velocity. The design makes use of an original architecture that is suitable for implantation and reduces the required data rate for transmission to units placed outside the body. Complete measured electrical data from samples of the ASICs are presented that show that the system has the capability to record signals of amplitude as low as 0.5 μV, which is adequate for the recording of naturally evoked ENG. In addition, measurements of electrically evoked ENG from the explanted sciatic nerves of Xenopus Laevis frogs are presented.


Cardioembolic but not other stroke subtypes predict mortality independent of stroke severity at presentation.
Introduction. Etiology of acute ischemic stroke (AIS) is known to significantly influence management, prognosis, and risk of recurrence. Objective. To determine if ischemic stroke subtype based on TOAST criteria influences mortality. Methods. We conducted an observational study of a consecutive cohort of patients presenting with AIS to a single tertiary academic center. Results. The study population consisted of 500 patients who resided in the local county or the surrounding nine-county area. No patients were lost to followup. Two hundred and sixty one (52.2%) were male, and the mean age at presentation was 73.7 years (standard deviation, SD = 14.3). Subtypes were as follows: large artery atherosclerosis 97 (19.4%), cardioembolic 144 (28.8%), small vessel disease 75 (15%), other causes 19 (3.8%), and unknown 165 (33%). One hundred and sixty patients died: 69 within the first 30 days, 27 within 31-90 days, 29 within 91-365 days, and 35 after 1 year. Low 90-, 180-, and 360-day survival was seen in cardioembolic strokes (67.1%, 65.5%, and 58.2%, resp.), followed for cryptogenic strokes (78.0%, 75.3%, and 71.1%). Interestingly, when looking into the cryptogenic category, those with insufficient information to assign a stroke subtype had the lowest survival estimate (57.7% at 90 days, 56.1% at 180 days, and 51.2% at 1 year). Conclusion. Cardioembolic ischemic stroke subtype determined by TOAST criteria predicts long-term mortality, even after adjusting for age and stroke severity.


Synthesis and characterization of cyclic pseudopeptide libraries containing thiomethylene and thiomethylene-sulfoxide amide bond surrogates.
We describe the first examples of a series of cyclic pseudopeptide libraries that have been prepared in a systematic approach in order to facilitate both synthesis and subsequent deconvolution attempts. Our synthetic strategy involved the attachment of a trifunctional amino acid (Asp, Asn or Glu) to a polystyrene resin via its side chain, and stepwise chain elongation using either protected amino acids or a pseudodipeptide building block. Head to tail cyclic peptides were formed by removal of the temporary N- and C-terminal protecting groups followed by ring closure by amide formation. Cyclization of the hexa, hepta, and octapseudopeptides on the resin avoided dimer formation, as monitored by mass spectrometry. We utilized a 'psi-scan' approach in which a second fixed position was serially addressed by stepping a dipeptide surrogate, Pro psi [CH2S]Gly around the rings to generate a group of cyclic pseudopeptide sub-libraries. Oxidation of psi [CH2S] to psi [CH2SO] helped validate the synthesis and also provides a strategy for forming a new set of pseudopeptide libraries (previously described as 'libraries from libraries'). Our results suggest that libraries of cyclic pseudopeptides are an efficient method of preparing and assaying these synthetically more challenging entities as potential drug leads.


Atomoxetine prevents dexamethasone-induced skeletal muscle atrophy in mice.
Skeletal muscle atrophy remains a clinical problem in numerous pathologic conditions. β2-Adrenergic receptor agonists, such as formoterol, can induce mitochondrial biogenesis (MB) to prevent such atrophy. Additionally, atomoxetine, an FDA-approved norepinephrine reuptake inhibitor, was positive in a cellular assay for MB. We used a mouse model of dexamethasone-induced skeletal muscle atrophy to investigate the potential role of atomoxetine and formoterol to prevent muscle mass loss. Mice were administered dexamethasone once daily in the presence or absence of formoterol (0.3 mg/kg), atomoxetine (0.1 mg/kg), or sterile saline. Animals were euthanized at 8, 16, and 24 hours or 8 days later. Gastrocnemius muscle weights, changes in mRNA and protein expression of peroxisome proliferator-activated receptor-γ coactivator-1 α (PGC-1α) isoforms, ATP synthase β, cytochrome c oxidase subunit I, NADH dehydrogenase (ubiquinone) 1 β subcomplex, 8, ND1, insulin-like growth factor 1 (IGF-1), myostatin, muscle Ring-finger protein-1 (muscle atrophy), phosphorylated forkhead box protein O 3a (p-FoxO3a), Akt, mammalian target of rapamycin (mTOR), and ribosomal protein S6 (rp-S6; muscle hypertrophy) in naive and muscle-atrophied mice were measured. Atomoxetine increased p-mTOR 24 hours after treatment in naïve mice, but did not change any other biomarkers. Formoterol robustly activated the PGC-1α-4-IGF1-Akt-mTOR-rp-S6 pathway and increased p-FoxO3a as early as 8 hours and repressed myostatin at 16 hours. In contrast to what was observed with acute treatment, chronic treatment (7 days) with atomoxetine increased p-Akt and p-FoxO3a, and sustained PGC-1α expression and skeletal muscle mass in dexamethasone-treated mice, in a manner comparable to formoterol. In conclusion, chronic treatment with a low dose of atomoxetine prevented dexamethasone-induced skeletal muscle wasting and supports a potential role in preventing muscle atrophy.


Oxidative stress and the evolutionary origins of preeclampsia.
In this speculative paper, I consider the relationship between oxidative stress and the evolution of placentation in eutherian mammals. I argue that epitheliochorial placentation, in which fetal tissues remain separated from maternal blood throughout gestation, has evolved as a protective mechanism against oxidative stress arising from pregnancy, particularly in species with unusually long gestation periods and unusually large placentas. Human beings comprise an unusual species that has the life history characteristics of an epitheliochorial species, but exhibits hemochorial placentation, in which fetal tissues come into direct contact with maternal blood. I argue that the risk of preeclampsia has arisen as a consequence of the failure of human beings to evolve epitheliochorial placentation.


Advantages and limitations of the Five Domains model for assessing welfare impacts associated with vertebrate pest control.
Many pest control activities have the potential to impact negatively on the welfare of animals, and animal welfare is an important consideration in the development, implementation and evaluation of ethically defensible vertebrate pest control. Thus, reliable and accurate methods for assessing welfare impacts are required. The Five Domains model provides a systematic method for identifying potential or actual welfare impacts associated with an event or situation in four physical or functional domains (nutrition, environment, health or functional status, behaviour) and one mental domain (overall mental or affective state). Here we evaluate the advantages and limitations of the Five Domains model for this purpose and illustrate them using specific examples from a recent assessment of the welfare impacts of poisons used to lethally control possums in New Zealand. The model has a number of advantages which include the following: the systematic identification of a wide range of impacts associated with a variety of control tools; the production of relative rankings of tools in terms of their welfare impacts; the easy incorporation of new information into assessments; and the highlighting of additional information needed. For example, a recent analysis of sodium fluoroacetate (1080) poisoning in possums revealed the need for more information on the period from the onset of clinical signs to the point at which consciousness is lost, as well as on the level of consciousness during or after the occurrence of muscle spasms and seizures. The model is also valuable because it clearly separates physical or functional and affective impacts, encourages more comprehensive consideration of negative affective experiences than has occurred in the past, and allows development and evaluation of targeted mitigation strategies. Caution must be used in interpreting and applying the outputs of the model, most importantly because relative rankings or grades are fundamentally qualitative in nature. Certain domains are more useful for evaluating impacts associated with slower/longer-acting tools than for faster-acting methods, and it may be easier to identify impacts in some domains than others. Overall, we conclude that the Five Domains model advances evaluation of the animal welfare impacts of vertebrate pest control methods, provided users are cognisant of its limitations.


Metabolic profiling for water-soluble metabolites in patients with schizophrenia and healthy controls in a Chinese population: A case-control study.
Objectives: Objective measures integrated with clinical symptoms may improve early prevention and detection of schizophrenia. Herein we aim to evaluate potential water-soluble metabolic biomarkers in schizophrenia.Methods: We recruited adults with schizophrenia (n = 113) who had not received pharmacological treatment for at least 1 month prior to enrollment and 111 age- and sex-matched healthy subjects from Weifang, Shandong province, China. All serum samples were analysed using liquid chromatography-tandem mass spectrometry coupled with a hydrophilic interaction liquid chromatography column.Results: Eleven metabolites, namely carnitines (oleoylcarnitine, l-palmitoylcarnitine, 9-decenoylcarnitine and 2-trans,4-cis-decadienoylcarnitine), polar lipids (lysophosphatidylcholine (LPC)(P-16:0), LPC (16:0), LPC (15:0) and LPC(14:0)), amino acids (taurine and l-arginine), and organic acid (2,5-dichloro-4-oxohex-2-enedioate), separated the patients and healthy controls. Compared with healthy controls, taurine, l-palmitoylcarnitine and oleoylcarnitine levels were higher, whereas the remaining eight metabolites were lower in patients with schizophrenia. A combination of four metabolites, i.e., oleoylcarnitine, 9-decenoylcarnitine, LPC (15:0) and LPC (14:0), provided the most robust between-group separation.Conclusions: This study appears to distinguish between groups of patients and controls, which should be considered as a contribution to putative potential biomarkers. The water-soluble metabolites were determined to be significantly different between the groups in the current study, and were primarily related to cellular bioenergetics, notably oxidative stress.


Prenatal exposure to endocrine disrupting chemicals and risk of being born small for gestational age: Pooled analysis of seven European birth cohorts.
There is evidence that endocrine disrupting chemicals (EDCs) have developmental effects at environmental concentrations. We investigated whether some EDCs are associated with the adverse birth outcome Small for Gestational Age (SGA). We used PCB 153, p,p'-DDE, HCB, PFOS and PFOA measured in maternal, cord blood or breast milk samples of 5446 mother-child pairs (subset of 693 for the perfluorinated compounds) from seven European birth cohorts (1997-2012). SGA infants were those with birth weight below the 10th percentile for the norms defined by gestational age, country and infant's sex. We modelled the association between measured or estimated cord serum EDC concentrations and SGA using multiple logistic regression analyses. We explored effect modification by child's sex and maternal smoking during pregnancy. Among the 5446 newborns, 570 (10.5%) were SGA. An interquartile range (IQR) increase in PCB 153 was associated with a modestly increased risk of SGA (odds ratio (OR) of 1.05 [95% CI: 1.04-1.07]) that was stronger in girls (OR of 1.09 [95% CI: 1.04-1.14]) than in boys (OR of 1.03 [95% CI: 1.03-1.04]) (p-interaction = 0.025). For HCB, we found a modestly increased odds of SGA in girls (OR of 1.04 [95% CI: 1.01-1.07] per IQR increase), and an inverse association in boys (OR of 0.90 [95% CI: 0.85-0.95]) (p-interaction = 0.0003). Assessment of the HCB-sex-smoking interaction suggested that the increased odds of SGA associated with HCB exposure was only in girls of smoking mothers (OR of 1.18 [95% CI: 1.11-1.25]) (p-interaction = 0.055). Higher concentrations of PFOA were associated with greater risk of SGA (OR of 1.64 [95% CI: 0.97-2.76]). Elevated PFOS levels were associated with increased odds of SGA in newborns of mothers who smoked during pregnancy (OR of 1.63 [95% CI: 1.02-2.59]), while an inverse association was found in those of non-smoking mothers (OR of 0.66 [95% CI: 0.61-0.72]) (p-interaction = 0.0004). No significant associations were found for p,p'-DDE. Prenatal environmental exposure to organochlorine and perfluorinated compounds with endocrine disrupting properties may contribute to the prevalence of SGA. We found indication of effect modification by child's sex and smoking during pregnancy. The direction of the associations differed by chemical and these effect modifiers, suggesting diverse mechanisms of action and biological pathways.


Unfolding bovine α-lactalbumin with T-jump: Characterizing disordered intermediates via time-resolved x-ray solution scattering and molecular dynamics simulations.
The protein folding process often proceeds through partially folded transient states. Therefore, a structural understanding of these disordered states is crucial for developing mechanistic models of the folding process. Characterization of unfolded states remains challenging due to their disordered nature, and incorporating multiple methods is necessary. Combining the time-resolved x-ray solution scattering (TRXSS) signal with molecular dynamics (MD), we are able to characterize transient partially folded states of bovine α-lactalbumin, a model system widely used for investigation of molten globule states, during its unfolding triggered by a temperature jump. We track the unfolding process between 20 µs and 70 ms and demonstrate that it passes through three distinct kinetic states. The scattering signals associated with these transient species are then analyzed with TRXSS constrained MD simulations to produce protein structures that are compatible with the input signals. Without utilizing any experimentally extracted kinetic information, the constrained MD simulation successfully drove the protein to an intermediate molten globule state; signals for two later disordered states are refined to terminal unfolded states. From our examination of the structural characteristics of these disordered states, we discuss the implications disordered states have on the folding process, especially on the folding pathway. Finally, we discuss the potential applications and limitations of this method.


Working memory in pregnant women: Relation to estrogen and antepartum depression.
This article is part of a Special Issue "Estradiol and cognition". Subjective changes in concentration and memory are commonly reported by women during the second or third trimesters of pregnancy, but the nature of the problem is poorly understood. We hypothesized that these self-reports might reflect difficulties in working memory (WM). It was further hypothesized that antepartum depression (depression arising during pregnancy) may play an etiological role, either on its own or due to secondary changes in endocrine function or sleep. Using WM tasks that emphasized executive control processes mediated by the prefrontal cortex (PFC) we compared pregnant women tested at 34-36 weeks of gestation (n = 28) with age- and education-matched non-pregnant controls (n = 26). All pregnant women were screened for depression. Evidence of a WM disturbance was found, and was evident only among pregnant women showing depressive symptoms. In contrast, pregnant women who were not depressed showed WM performance that equalled, or even significantly exceeded, non-pregnant controls. No significant differences were observed on control tests of other cognitive functions. Multiple regression revealed that serum estradiol concentrations, along with severity of depressive affect but not sleep disruption, significantly predicted variation in the WM scores. In agreement with studies of estradiol and WM in other contexts, higher estradiol was associated with better WM, while higher levels of depressive symptoms predicted poorer WM. We conclude that memory disturbance during gestation might not be as widespread as commonly believed, but can be seen among women experiencing antepartum depression. The high level of WM performance found in healthy, non-depressed, pregnant women is discussed from an adaptationist perspective.


Ultrasonographic morphometric measurements of digital flexor tendons and ligaments of the palmar metacarpal region in Haflinger horses.
The aim of the study was to determine morphometric values of the superficial and deep digital flexor tendon, the inferior check ligament and the suspensory ligament in the palmar metacarpal region of sound Haflinger horses using ultrasonography and to assess the influence of different factors on them. The findings were compared with the literature. A total of 30 sound Haflinger mares aged 4-20 years were used. Transverse ultrasound images were obtained with an 8-10 linear MHz transducer and the cross-sectional area, the circumference and the dorsopalmar and lateromedial width were determined for each structure at six regions of interest (ROI) in both forelimbs. The coefficient of variation was <3%. The structures were compared between each other and the values of each structure at the ROIs. Age, height at the withers, body mass index, diameter of the Os metacarpale III and the circumference of the mid-metacarpal region showed significant influences on some of the parameters. Reference values for the tendons and ligaments in the palmar metacarpal region in sound Haflinger mares were obtained and the influence of different factors was tested. Description of the dimensional relationship between the structures and comparison of the data with the literature provide knowledge required for adequate veterinary care.


Population admixture and high larval viability among urban toads.
In terms of evolutionary biology, a population admixture of more than two distinct lineages may lead to strengthened genetic variation through hybridization. However, a population admixture arising from artificial secondary contact poses significant problems in conservation biology. In urban Tokyo, a population admixture has emerged from two lineages of Japanese common toad: native Bufo japonicus formosus and nonnative B. japonicus japonicus, of which the latter was introduced in the early 20th century. To evaluate the degree of genetic disturbance in the admixed population of these two subspecies, we analyzed genotypes of toads distributed within and outside Tokyo by assessing mtDNA and seven microsatellite loci. We found that the introduced B. japonicus japonicus genotype dominates six local populations in the Tokyo admixture zone and was clearly derived from past introgressive hybridization between the two subspecies. These observations were supported by morphological assessments. Furthermore, the average larval survival rate in Tokyo was significantly higher than that outside Tokyo, suggesting that the temporary contribution of introduced toads occurred through introgression. The fitness of toads in urban Tokyo may thus be increasing with the assistance of nonnative individuals.


Automated Calculation of Cochlear Implant Electrode Insertion Parameters in Clinical Cone-Beam CT.
Automated processing of postoperative clinical cone-beam CT (CBCT) of cochlear implant (CI) patients can be used to accurately determine electrode contacts and integrated with an atlas-based mapping of cochlear microstructures to calculate modiolar distance, angular insertion distance, and scalar location of electrode contacts. Hearing outcomes after CI surgery are dependent on electrode placement. CBCT is increasingly used for in-office temporal bone imaging and might be routinely used for pre- and post-surgical evaluation. Thirty-six matched pairs of pre- and postimplant CBCT scans were obtained. These were registered with an atlas to model cochlear microstructures in each dataset. Electrode contact center points were automatically determined using thresholding and electrode insertion parameters were calculated. Automated localization and calculation were compared with manual segmentation of contact center points as well as manufacturer specifications. Automated electrode contact detection aligned with manufacturer specifications of spacing and our algorithms worked for both distantly- and closely spaced arrays. The average difference between the manual and the automated selection was 0.15 mm, corresponding to a 1.875 voxel difference in each plane at the scan resolution. For each case, we determined modiolar distance, angular insertion depth, and scalar location. These calculations also resulted in similar insertion values using manual and automated contact points as well as aligning with electrode properties. Automated processing of implanted high-resolution CBCT images can provide the clinician with key information on electrode placement. This is one step toward routine use of clinical CBCT after CI surgery to inform and guide postoperative treatment.


Acute progressive neurological decline in an elderly man.
The patient was an 88-year-old man referred to a physical therapist by his primary care physician for a 1-week history of severe neck pain of insidious onset. Based upon the history and physical examination, the physical therapist concluded that the patient's neck pain was mechanical in nature. Initial physical therapist intervention included cervical taping, cervical collar use and instruction in home exercise. At his follow-up visit 4 days after his initial physical therapy visit, the patient reported no improvement. The patient's son, who accompanied him to this visit, also reported that his father had a recent onset of fever and mild confusion. The case was discussed with the patient's physician and it was recommended that the patient report to the emergency department. Evaluation in the emergency department revealed that the patient was febrile with diminished oxygen saturation and an elevated white blood cell count. Chest radiographs were consistent with pneumonia and blood cultures were positive for methicillin-resistant Staphylococcus aureus. The patient was hospitalized and over the next 6 days, his condition progressively declined and quadriplegia below the C4 myotomal level developed. Magnetic resonance imaging of the cervical spine revealed severe cervical central canal stenosis with extensive signal abnormality in the cervical cord, as well as diffuse oedema in the perivertebral soft tissues that was consistent with a retropharyngeal abscess. Despite medical management, the patient subsequently succumbed to the complications of pneumonia and quadriplegia.


Bio-inspired self-propelled diatom micromotor by catalytic decomposition of H2O2 under low fuel concentration.
Recently, active bubble-propelled micromotors have attracted great attention for fuel applications. However, for generating bubble-propelled micromotors, additional catalysts, such as Pt, Ag, and Ru, are required. These catalysts are expensive, toxic, and highly unstable for broad applications. To overcome these issues, in this study, we present an innovative methodology for the preparation of self-propelled motor machines using naturally occurring diatom frustules. This natural diatom motor shows effective motion in the presence of a very low concentration (0.8%) of H2O2 as a fuel at pH 7. Due to the unique 3D anisotropic shape of the diatom, the self-propelled motor exhibited unidirectional motion with a speed of 50 μm s-1 and followed pseudo first-order kinetics. It was found that a trace amount of iron oxide (Fe2O3) in the diatom was converted into Fe3O4, which can act as a catalyst to achieve the facile decomposition of H2O2. Interestingly, "braking" of the unidirectional motion was observed upon treatment with EDTA, which blocked the catalytically active site. These results illustrate that diatom catalytic micromotors have opened a new era in the field of catalysis and bioengineering applications.