Regulation of fasted blood glucose by resistin.
The association between obesity and diabetes supports an endocrine role for the adipocyte in maintaining glucose homeostasis. Here we report that mice lacking the adipocyte hormone resistin exhibit low blood glucose levels after fasting, due to reduced hepatic glucose production. This is partly mediated by activation of adenosine monophosphate-activated protein kinase and decreased expression of gluconeogenic enzymes in the liver. The data thus support a physiological function for resistin in the maintenance of blood glucose during fasting. Remarkably, lack of resistin diminishes the increase in post-fast blood glucose normally associated with increased weight, suggesting a role for resistin in mediating hyperglycemia associated with obesity.


Receiver operating characteristic analysis of eyewitness memory: comparing the diagnostic accuracy of simultaneous versus sequential lineups.
A police lineup presents a real-world signal-detection problem because there are two possible states of the world (the suspect is either innocent or guilty), some degree of information about the true state of the world is available (the eyewitness has some degree of memory for the perpetrator), and a decision is made (identifying the suspect or not). A similar state of affairs applies to diagnostic tests in medicine because, in a patient, the disease is either present or absent, a diagnostic test yields some degree of information about the true state of affairs, and a decision is made about the presence or absence of the disease. In medicine, receiver operating characteristic (ROC) analysis is the standard method for assessing diagnostic accuracy. By contrast, in the eyewitness memory literature, this powerful technique has never been used. Instead, researchers have attempted to assess the diagnostic performance of different lineup procedures using methods that cannot identify the better procedure (e.g., by computing a diagnosticity ratio). Here, we describe the basics of ROC analysis, explaining why it is needed and showing how to use it to measure the performance of different lineup procedures. To illustrate the unique advantages of this technique, we also report 3 ROC experiments that were designed to investigate the diagnostic accuracy of simultaneous versus sequential lineups. According to our findings, the sequential procedure appears to be inferior to the simultaneous procedure in discriminating between the presence versus absence of a guilty suspect in a lineup.


Increase in the degree of coexpression of myosin heavy chain isoforms in skeletal muscle fibers of the very old.
Myosin heavy chain (MHC) isoform composition was determined in 2264 single skeletal muscle fibers from vastus lateralis muscle of a group (n = 12) of very old subjects (average age, 88 years). The number of fibers containing only MHC I, IIA, or IIX was 19.9%, 27.2%, and 0.3%, respectively. Surprisingly, 28.5% of the fibers displayed coexpression of both MHC I and IIA, a phenotype that is present in younger adults in very small percentages. Among these fibers coexpressing MHC I and IIA, the majority had a dominant expression of MHC I. Additionally, a small number of fibers coexpressing MHC I and IIX without any MHC IIA, and fibers co-expressing all three isoforms were observed. Altogether, 52.6% of all fibers examined in these very old subjects coexpressed two or three MHC isoforms. The present study provides evidence that advanced age leads to a significant elevation of skeletal muscle fibers displaying coexpression of two MHC isoforms and that a separation into slow and fast fibers in very old individuals may therefore be somewhat misleading. The clinical significance of the elevated number of fibers coexpressing MHC I and IIA is uncertain.


Health evaluation of free-ranging Humboldt penguins (Spheniscus humboldti) in Peru.
As part of ongoing ecological studies of Humboldt penguins (Spheniscus humboldti) at Punta San Juan, Ica Department, Peru, health surveys were conducted in November 1992, 1993, and 1994. In the three surveys, 98 birds in total were handled for examination, and blood was collected for laboratory analysis from 90 of these birds. All birds seemed to be in good condition. Body weights of females were significantly lower in 1994 than in the other years. Fleas (Parapsyllus humboldti) and ticks (Ornithodoros amblus) were found on the penguins and in their nests. Females had significantly higher plasma calcium and phosphorus levels, and they had lower weights than males. No other differences were found between the sexes. Hematology, plasma chemistries, and plasma mineral levels varied between years. Positive antibody titers for Chlamydophila psittaci (62%), avian adenovirus (7%; 1994 only), paramyxovirus-2 (7%; 1993 only), and Salmonella Pullorum (7%) were found. Plasma chemistry and mineral levels differed between individuals testing positive vs. negative on serologic tests for avian adenovirus and Salmonella Pullorum. Serologic tests for antibodies to avian influenza A virus, avian encephalomyelitis virus, infectious bronchitis virus, avian reovirus, duck viral enteritis virus, equine encephalitis (eastern, western, and Venezuelan) viruses, infectious bursal disease virus, infectious laryngotracheitis virus, Aspergillus sp., and paramyxovirus-1 and -3 were negative. All chlorinated pesticide and polychlorinated biphenyl analyses were below detectable limits.


Switching of Magnons by Electric and Magnetic Fields in Multiferroic Borates.
Electric manipulation of magnetic properties is a key problem of materials research. To fulfill the requirements of modern electronics, these processes must be shifted to high frequencies. In multiferroic materials, this may be achieved by electric and magnetic control of their fundamental excitations. Here we identify magnetic vibrations in multiferroic iron borates that are simultaneously sensitive to external electric and magnetic fields. Nearly 100% modulation of the terahertz radiation in an external field is demonstrated for SmFe_{3}(BO_{3})_{4}. High sensitivity can be explained by a modification of the spin orientation that controls the excitation conditions in multiferroic borates. These experiments demonstrate the possibility to alter terahertz magnetic properties of materials independently by external electric and magnetic fields.


Abdominal aortic calcification in dialysis patients: results of the CORD study.
Patients with chronic kidney disease stage 5 have a high prevalence of vascular calcification, but the specific anatomical distribution and severity of abdominal aortic calcification (AAC), in contrast to coronary calcification, is less well documented. AAC may be recorded using plain radiographs. The present report is an analysis of baseline data on AAC in patients enrolled in the CORD (Calcification Outcome in Renal Disease) study. A total of 47 centres in six European countries participated in this cross-sectional study. Inclusion criteria were age >or=18 years and duration of dialysis >or=3 months. Lateral lumbar radiography of the abdominal aorta was used to determine the overall AAC score, which is related to the severity of calcific deposits at lumbar vertebral segments L1-L4. The reliability of the method was tested by double reading of 64 radiographs (coefficient of correlation 0.9). A lateral lumbar radiograph was obtained in 933 patients. Calcification (AAC score >or= 1) was present in 81% of the patients; its severity increased significantly from L1 to L4 (P < 0.0001) and affected all of these segments in 51% of patients. Independent predictors for the presence and severity of calcification were age (odds ratio [OR] 1.103/year; P < 0.0001), duration of dialysis (OR 1.110/year; P = 0.002) and history of cardiovascular disease (OR 3.247; P < 0.0001). AAC detected by lateral lumbar radiograph is associated with several risk factors of uraemic calcification. This semi-quantitative method is more widely available and less expensive than the current procedures for studying calcification and could form part of a pre-transplant workup and cardiovascular risk stratification.


Multilabel Classification Models for the Prediction of Cross-Coupling Reaction Conditions.
Machine-learned ranking models have been developed for the prediction of substrate-specific cross-coupling reaction conditions. Data sets of published reactions were curated for Suzuki, Negishi, and C-N couplings, as well as Pauson-Khand reactions. String, descriptor, and graph encodings were tested as input representations, and models were trained to predict the set of conditions used in a reaction as a binary vector. Unique reagent dictionaries categorized by expert-crafted reaction roles were constructed for each data set, leading to context-aware predictions. We find that relational graph convolutional networks and gradient-boosting machines are very effective for this learning task, and we disclose a novel reaction-level graph attention operation in the top-performing model.


Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease.
We sought to examine the relationship between C-reactive protein (CRP) and clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease (IBD). All IBD patients at our institution between January 2002 and August 2003 who had a CRP, colonoscopy, and either small bowel follow-through (SBFT) or CT enterography (CTE) performed within 14 days were identified. Clinical activity was assessed retrospectively through review of the medical record. Logistic regression was used in Crohn's disease (CD) patients to estimate the odds ratio (OR) with 95% confidence intervals for an elevated CRP. Associations were assessed using Fisher exact test in ulcerative colitis (UC) patients due to small sample size. One-hundred four CD patients (46% males) and 43 UC and indeterminate colitis patients (44% males) were identified. In CD patients, moderate-severe clinical activity (OR, 4.5; 95% CI, 1.1-18.3), active disease at colonoscopy (OR, 3.5; 95% CI, 1.4-8.9), and histologically severe inflammation (OR, 10.6; 95% CI; 1.1-104) were all significantly associated with CRP elevation. Abnormal small bowel radiographic imaging was not significantly associated with CRP elevation. In UC patients, CRP elevation was significantly associated with severe clinical activity, elevation in sedimentation rate, anemia, hypoalbuminemia, and active disease at ileocolonoscopy, but not with histologic inflammation. CRP elevation in IBD patients is associated with clinical disease activity, endoscopic inflammation, severely active histologic inflammation (in CD patients), and several other biomarkers of inflammation, but not with radiographic activity.


A qualitative investigation of attitudes towards aerobic and resistance exercise amongst overweight and obese individuals.
Most people are not meeting the minimal requirements for physical activity participation, particularly people who are overweight or obese. Numerous initiatives have been developed which aim to increase levels of physical activity in this group, yet little is known about their feelings towards different types of exercise. In particular, resistance exercise may offer unique benefits to people seeking to lose weight, yet no study to date has examined views of resistance exercise amongst the overweight and obese. This qualitative study examined the views and attitudes towards aerobic and resistance exercise amongst overweight and obese individuals engaged in a weight management clinic. 30 overweight and obese patients comprised of 25 females and 5 males, with a mean age of 40.7 years (SD = 15.2) and mean BMI of 33.8 kg/m2 (SD = 7.9) were recruited from a dietetic clinic to take part in baseline focus groups and interviews to assess their views on physical activity. After selecting and participating in a 12 week aerobic- or resistance-exercise program, the participants took part in follow-up interviews. Thematic analysis was then performed on the transcribed focus group and interview data. For the overweight and obese women in this study, weight loss was the primary motivation for physical activity participation. Subsequently, these women perceived a failure to lose weight as strongly affecting their motivation to continue or re-engage in physical activity. Only 3 participants selected the resistance exercise option. The view of resistance exercise as a masculine activity was a dominant theme amongst all participants. A lack of knowledge of how to perform certain exercises emerged as a barrier, but was seen by the participants as surmountable given appropriate instruction. The females in this study cited weight loss as a primary motivation for physical activity participation. This view must be reconciled with the existing knowledge base of physical activity requirements for successful weight loss and maintenance. Participants in this study had little awareness or experience of resistance exercise, and many were fearful of the potential risks.


Polyamines and cellular metabolism in plants: transgenic approaches reveal different responses to diamine putrescine versus higher polyamines spermidine and spermine.
Distribution of biogenic amines-the diamine putrescine (Put), triamine spermidine (Spd), and tetraamine spermine (Spm)-differs between species with Put and Spd being particularly abundant and Spm the least abundant in plant cells. These amines are important for cell viability and their intracellular levels are tightly regulated, which have made it difficult to characterize individual effects of Put, Spd and Spm on plant growth and developmental processes. The recent transgenic intervention and mutational genetics have made it possible to stably alter levels of naturally occurring polyamines and study their biological effects. We bring together an analysis of certain metabolic changes, particularly in amino acids, to infer the responsive regulation brought about by increased diamine or polyamine levels in actively growing poplar cell cultures (transformed with mouse ornithine decarboxylase gene to accumulate high Put levels) and ripening tomato pericarp (transformed with yeast S-adenosylmethionine decarboxylase gene to accumulate high Spd and Spm levels at the cost of Put). Our analysis indicates that increased Put has little effect on increasing the levels of Spd and Spm, while Spd and Spm levels are inter-dependent. Further, Put levels were positively associated with Ala (alpha and beta), Ile and GABA and negatively correlated with Gln and Glu in both actively growing poplar cell cultures and non-dividing tomato pericarp tissue. Most amino acids showed positive correlations with Spd and Spm levels in actively growing cells. Collectively these results suggest that Put is a negative regulator while Spd-Spm are positive regulators of cellular amino acid metabolism.


Predicting premature termination within a randomized controlled trial for binge-eating patients.
Understanding the dropout rates of efficacious forms of psychotherapy for patients with binge eating disorder (BED) is an unsolved problem within this increasing population. Up until now the role of psychotherapy process characteristics as predictors of premature termination has not been investigated in the BED literature. Within a randomized controlled trial (N=78) we investigated the degree to which early psychological process characteristics, such as components of the therapeutic relationship and the experiences of mastery and motivational clarification, predicted premature termination of treatment. We statistically controlled for the influences of covariates such as rapid response of treatment, treatment group, body mass index, Axis II disorder, and patients' preexisting generalized self-efficacy at baseline. Patients' postsession reports from Sessions 1 to 5 indicated that low self-esteem in-session experiences was a stable predictor of premature termination. Its predictive value persisted after controlling for the above-mentioned covariates. Exploratory analyses further revealed low self-esteem experiences, low global alliance, and low mastery and clarification experiences as predictors in those patients who explicitly specified discontentment with therapy as reason for premature termination. These results indicate that patients' self-esteem experiences may not be an epiphenomenon of their specific psychopathology but may represent general mechanisms on which remaining or withdrawing from psychotherapeutic treatment depends. Early psychotherapy process characteristics should therefore be considered in training and evaluation of psychotherapists carrying through BED treatments.


Cost-effectiveness analysis of a randomized trial comparing care models for chronic kidney disease.
Potential cost and effectiveness of a nephrologist/nurse-based multifaceted intervention for stage 3 to 4 chronic kidney disease are not known. This study examines the cost-effectiveness of a chronic disease management model for chronic kidney disease. Cost and cost-effectiveness were prospectively gathered alongside a multicenter trial. The Canadian Prevention of Renal and Cardiovascular Endpoints Trial (CanPREVENT) randomized 236 patients to receive usual care (controls) and another 238 patients to multifaceted nurse/nephrologist-supported care that targeted factors associated with development of kidney and cardiovascular disease (intervention). Cost and outcomes over 2 years were examined to determine the incremental cost-effectiveness of the intervention. Base-case analysis included disease-related costs, and sensitivity analysis included all costs. Consideration of all costs produced statistically significant differences. A lower number of days in hospital explained most of the cost difference. For both base-case and sensitivity analyses with all costs included, the intervention group required fewer resources and had higher quality of life. The direction of the results was unchanged to inclusion of various types of costs, consideration of payer or societal perspective, changes to the discount rate, and levels of GFR. The nephrologist/nurse-based multifaceted intervention represents good value for money because it reduces costs without reducing quality of life for patients with chronic kidney disease.


Saccharospirillum mangrovi sp. nov., a bacterium isolated from mangrove sediment.
A Gram-negative, spirilla, non-spore-forming, motile and strictly aerobic bacterium, designated HK-33T, was isolated from a mangrove sediment sample in Haikou city, Hainan Province, China. Strain HK-33T was able to grow at 10-45 °C (optimum 37 °C), 0.5-12.0 % (w/v) NaCl (2.0 %, w/v) and pH 5.5-8.5 (pH 7.0). The major cellular fatty acids were C16 : 0 and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). Ubiquinone-8 was the predominant respiratory quinone, and Q-9 was present in trace amounts. The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, two unidentified phospholipids, two unidentified glycolipids, an unidentified aminophosphoglycolipid and two unidentified lipids. The DNA G+C content was 57.3 mol%. According to 16S rRNA gene sequences similarity, strain HK-33T shared 98.6 %, 96.4%, 95.7 and 94.9 % sequence similarities to the species Saccharospirillum correiae CPA1T, Saccharospirillum impatiens EL-105T, Saccharospirillum salsuginis YIM-Y25T and Saccharospirillum aestuarii IMCC 4453T, respectively. Phylogenetic analysis showed that strain HK-33T was clustered with S. correiae CPA1T, S. impatiens EL-105T, S. salsuginis YIM-Y25T and S. aestuarii IMCC 4453T. Results of DNA-DNA hybridization analysis revealed that strain HK-33T shared 36.3±1.7 % DNA relatedness with S. correiae CPA1T. On the basis of its phenotypic, chemotaxonomic and genotypic characteristics, strain HK-33T is considered to represent a novel species in the genus Saccharospirillum, for which the name Saccharospirillummangrovi sp. nov. is proposed. The type strain is HK-33T (=KCTC 62178T=MCCC 1K03440T).


Food literacy and diet quality in young vegans, lacto-ovo vegetarians, pescatarians, flexitarians and omnivores.
To investigate whether food literacy competencies and diet quality vary between 16-to-24-year-olds vegans, lacto-ovo vegetarians, pescatarians, flexitarians and omnivores and to assess whether food literacy is associated with diet quality. Cross-sectional study. Food literacy (general nutrition knowledge, critical nutrition literacy and food skills) and diet quality were measured using an electronic questionnaire. Southern Norway, September 2021 - March 2022. Healthy 16-24-year-olds (n 165). Overall, the mean general nutrition knowledge score was moderate (48·0 out of 67·0); the lowest mean score was found in omnivores and the highest in flexitarians (45·6 v. 51·5) (P = 0·034). The mean score of critical nutrition literacy was also moderate (3·7 out of 5·0); vegans showed higher scores compared to other dietary practices (P = 0·018). No difference was observed in food skills between the different dietary practices. The overall median diet quality score was 46·0 out of 80·0, lowest in omnivores and highest in vegans (42·0 v. 56·0) (P =< 0·001). In multivariate regression analyses, general nutrition knowledge, food skills and vegan dietary practice were significantly associated with higher diet quality. We found moderate levels of food literacy across all dietary practices. The food literacy competencies, general nutrition knowledge and food skills were associated with higher diet quality in our sample. Omnivores showed both the lowest general nutrition knowledge level and lowest diet quality scores. In contrast, both flexitarians and vegans scored highest on general nutrition knowledge and diet quality scores, despite being one of the less restrictive and one of the strictest plant-based dietary practices, respectively.


Polysaccharide antigens of the capsule of Cryptococcus neoformans.
The major significance of the capsular polysaccharide of C. neoformans is its role in potentiating opportunistic infections by the yeast. It has the ability to exert a broad spectrum of influences on the immune response, from activation of phagocytic cells and complement components of the alternative pathway, to the induction of specific antibody, T-suppressor cells, DTH responses, and cytokines (51). These biological properties along with the serotype specificities are all determined by the physical properties and chemical structures of the polysaccharide antigens that compose the capsule. There is evidence not only for an association of lethal infections with serotype A in patients with advanced AIDS (34, 56), but also for a role for the capsule in directly influencing the infection of CD4+ cells by HIV (57). Together, these phenomena raise intriguing questions about the possible connection between the chemistry of these capsular antigens and cryptococcal infections in AIDS patients. One speculation is that AIDS creates the optimal physiological conditions for the establishment and spread of cryptococcosis. It has been observed that during the progression of AIDS there is a shift towards a T-2 response (14). This could lead to conditions that would inhibit the cellular immune responses that block dissemination of cryptococcal infections. Thus, an important consideration in the application of vaccine or immune modulation therapies in the treatment of cryptococcosis in AIDS victims would be the design of vaccines that could boost the T-1 immune response. It has been shown that the form and dose of an antigenic challenge can influence the induction of a T-1 or T-2 immune response (61). Recently, Murphy has reported that gamma interferon and interleukin 2 are up-regulated in the spleens of mice that produce anticryptococcal TDH and TAMP cells in response to immunogenic doses of cryptococcal culture filtrate antigen given with Freund's complete adjuvant (49). Perhaps purified cryptococcal antigens (e.g., MP) conjugated to an appropriate carrier or adjuvant could be used in therapeutic strategies to limit cryptococcosis in immunocompromised individuals. Future investigations of virulence and pathogenicity in the context of defined polysaccharide antigens from encapsulated strains of C. neoformans will contribute to a better understanding of the regulation of cryptococcal infection and immunity at the cellular and molecular levels.(ABSTRACT TRUNCATED AT 400 WORDS)


Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans.
A key challenge of functional genomics today is to generate well-annotated data sets that can be interpreted across different platforms and technologies. Large-scale functional genomics data often fail to connect to standard experimental approaches of gene characterization in individual laboratories. Furthermore, a lack of universal annotation standards for phenotypic data sets makes it difficult to compare different screening approaches. Here we address this problem in a screen designed to identify all genes required for the first two rounds of cell division in the Caenorhabditis elegans embryo. We used RNA-mediated interference to target 98% of all genes predicted in the C. elegans genome in combination with differential interference contrast time-lapse microscopy. Through systematic annotation of the resulting movies, we developed a phenotypic profiling system, which shows high correlation with cellular processes and biochemical pathways, thus enabling us to predict new functions for previously uncharacterized genes.


Detection of anthropogenic climate change in the world's oceans.
Large-scale increases in the heat content of the world's oceans have been observed to occur over the last 45 years. The horizontal and temporal character of these changes has been closely replicated by the state-of-the-art Parallel Climate Model (PCM) forced by observed and estimated anthropogenic gases. Application of optimal detection methodology shows that the model-produced signals are indistinguishable from the observations at the 0.05 confidence level. Further, the chances of either the anthropogenic or observed signals being produced by the PCM as a result of natural, internal forcing alone are less than 5%. This suggests that the observed ocean heat-content changes are consistent with those expected from anthropogenic forcing, which broadens the basis for claims that an anthropogenic signal has been detected in the global climate system. Additionally, the requirement that modeled ocean heat uptakes match observations puts a strong, new constraint on anthropogenically forced climate models. It is unknown if the current generation of climate models, other than the PCM, meet this constraint.


Improved detection of chromosomal abnormalities in chronic lymphocytic leukemia by conventional cytogenetics using CpG oligonucleotide and interleukin-2 stimulation: A Belgian multicentric study.
We performed a multicentric study to assess the impact of two different culture procedures on the detection of chromosomal abnormalities in 217 consecutive unselected cases with chronic lymphocytic leukemia (CLL) referred for routine analysis either at the time of diagnosis (n = 172) or during disease evolution (n = 45). Parallel cultures of peripheral blood or bone marrow were set up with the addition of either the conventional B-cell mitogen 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or a combination of CpG oligonucleotide (CpG) and interleukin-2 (IL-2). Cytogenetic analyses were performed on both cultures. Clonal abnormalities were identified in 116 cases (53%). In 78 cases (36%), the aberrant clone was detected in both cultures. Among these, the percentages of aberrant metaphases were similar in both conditions in 17 cases, higher in the CpG/IL-2 culture in 43 cases, and higher in the TPA culture in 18 cases. Clonal aberrations were detected in only one culture, either in CpG/IL-2 or TPA in 33 (15%) and 5 (2%) cases, respectively. Taken together, abnormal karyotypes were observed in 51% with CpG/IL-2 and 38% with TPA (P < 0.0001). Application of FISH (n = 201) allowed the detection of abnormalities not visible by conventional cytogenetic analysis in 80 cases: del(13q) (n = 71), del(11q) (n = 5), +12 (n = 2), del(14q) (n = 1), and del(17p) (n = 1). In conclusion, our results confirm that CpG/IL-2 stimulation increases the detection rate of chromosomal abnormalities in CLL compared with TPA and that further improvement can be obtained by FISH. However, neither conventional cytogenetics nor FISH detected all aberrations, demonstrating the complementary nature of these techniques.


A giant popliteal lipoblastoma in a 23-month-old girl: a case report.
Lipoblastomas are rare benign tumors that arise from embryonic white fat and almost always occur in babies and children. Here, we report a case of a giant popliteal lipoblastoma in a 23-month-old Japanese girl that was successfully treated via complete resection. Our patient was a 23-month-old Japanese girl. At 6 months of age, she presented at a nearby hospital with a mass on the popliteal side of her lower right leg. She had no symptoms and was diagnosed as having a benign adipose tumor via magnetic resonance imaging. The mass gradually increased in size, and she was referred to our hospital at 1 year and 11 months of age. A physical examination and radiology revealed a localized mass 13 × 10 × 7 cm in size in the aforementioned area that restricted knee movement and caused proximal tibia deformity. Magnetic resonance imaging showed a giant circumscribed subcutaneous mass with multiple partitions that was hyperintense on T1-weighted and T2-weighted images but not fat-saturated on T2-weighted images. Based on these findings, she was diagnosed as having a lipoblastoma. Because the mass surrounded her popliteal artery and vein and part of the popliteal nerve, surgical resection was considered risky, and we opted to simply observe her. However, owing to rapid growth of the mass and the worsening of symptoms, she underwent complete resection at 2 years and 6 months of age. A histological examination confirmed the diagnosis of a lipoblastoma. She was discharged from our hospital 3 days after surgery with no symptoms. She could walk without pain at the 6-month follow-up, and no local recurrence was observed. We successfully treated a giant popliteal lipoblastoma without complications by performing a total resection. Our report provides evidence that lipoblastomas should be considered for surgical resection when they progress or symptoms appear.


When Homoplasy Is Not Homoplasy: Dissecting Trait Evolution by Contrasting Composite and Reductive Coding.
The conceptualization and coding of characters is a difficult issue in phylogenetic systematics, no matter which inference method is used when reconstructing phylogenetic trees or if the characters are just mapped onto a specific tree. Complex characters are groups of features that can be divided into simpler hierarchical characters (reductive coding), although the implied hierarchical relational information may change depending on the type of coding (composite vs. reductive). Up to now, there is no common agreement to either code characters as complex or simple. Phylogeneticists have discussed which coding method is best but have not incorporated the heuristic process of reciprocal illumination to evaluate the coding. Composite coding allows to test whether 1) several characters were linked resulting in a structure described as a complex character or trait or 2) independently evolving characters resulted in the configuration incorrectly interpreted as a complex character. We propose that complex characters or character states should be decomposed iteratively into simpler characters when the original homology hypothesis is not corroborated by a phylogenetic analysis, and the character or character state is retrieved as homoplastic. We tested this approach using the case of fruit types within subfamily Cinchonoideae (Rubiaceae). The iterative reductive coding of characters associated with drupes allowed us to unthread fruit evolution within Cinchonoideae. Our results show that drupes and berries are not homologous. As a consequence, a more precise ontology for the Cinchonoideae drupes is required.


The relation between structural, rugometric and fractal characteristics of hard dental tissues at micro and nano levels.
Human tooth exhibits a structure of a mixture of inorganic hydroxyapatite nanocrystals and organic phases. The aim of this study is to investigate different tissues of human canine teeth surface along with the micro structure parameters of each tissue. X-ray diffraction (XRD) is used to study the amorphous or crystalline nature of each tissue with different mineral compositions and crystalline structures where the highest crystalline quality is related to enamel. The surfaces are also examined by energy-dispersive X-ray spectrometry. Moreover, crystalline quality factor is carried out to estimate the crystallinity of the tissues. Also, based on the basic Scherrer equation, the Williamson-Hall equation is applied to extend the formula for the XRD. Enamel and cementum tissues of a typical human tooth, which look similar, are composed of a large variety of wide lines with different widths through Raman spectra analysis. In addition, the applied scanning electron microscopy extracts similar morphology for all tissues with round granular structures which are denser in the cementum. Atomic force microscopy is finally used for investigation of micro-morphologies of the different tissues and the results are compared with the fractal analysis which ends to the bifractal and anisotropic nature of enamel and cementum along with monofractal and isotropic nature of dentin.


Contribution of APC and MUTYH mutations to familial adenomatous polyposis susceptibility in Hungary.
Familial adenomatous polyposis (FAP) is a colorectal cancer predisposition syndrome with considerable genetic and phenotypic heterogeneity, defined by the development of multiple adenomas throughout the colorectum. FAP is caused either by monoallelic mutations in the adenomatous polyposis coli gene APC, or by biallelic germline mutations of MUTYH, this latter usually presenting with milder phenotype. The aim of the present study was to characterize the genotype and phenotype of Hungarian FAP patients. Mutation screening of 87 unrelated probands from FAP families (21 of them presented as the attenuated variant of the disease, showing <100 polyps) was performed using DNA sequencing and multiplex ligation-dependent probe amplification. Twenty-four different pathogenic mutations in APC were identified in 65 patients (75 %), including nine cases (37.5 %) with large genomic alterations. Twelve of the point mutations were novel. In addition, APC-negative samples were also tested for MUTYH mutations and we were able to identify biallelic pathogenic mutations in 23 % of these cases (5/22). Correlations between the localization of APC mutations and the clinical manifestations of the disease were observed, cases with a mutation in the codon 1200-1400 region showing earlier age of disease onset (p < 0.003). There were only a few, but definitive dissimilarities between APC- and MUTYH-associated FAP in our cohort: the age at onset of polyposis was significantly delayed for biallelic MUTYH mutation carriers as compared to patients with an APC mutation. Our data represent the first comprehensive study delineating the mutation spectra of both APC and MUTYH in Hungarian FAP families, and underscore the overlap between the clinical characteristics of APC- and MUTYH-associated phenotypes, necessitating a more appropriate clinical characterization of FAP families.


Validation and application of the M.D. Anderson Dysphagia Inventory in patients treated for head and neck cancer in Brazil.
Analysis of quality of life (QOL) has revealed that preservation of swallowing, speech, and breathing functions has a direct impact on QOL and that these functions are important patient-reported outcomes. The purposes of this study were to adapt and culturally validate the M.D. Anderson Dysphagia Inventory (MDADI) to the Brazilian Portuguese language and to evaluate QOL related to dysphagia in patients treated for head and neck cancer. This was a cross-sectional study that included 72 adult patients with a mean age of 63 years who were treated for head and neck cancer. Construct validity and reliability analyses were performed through the comparison of the MDADI with three other health-related QOL questionnaires administered at the time of enrollment and MDADI application 2 weeks thereafter, respectively. Reliability was established by assuring both internal consistency (Cronbach's α) and test-retest reliability (intraclass correlation coefficient, ICC). Test-retest reliability for the total score in the MDADI had an ICC greater than 0.795 (p < 0.001). The MDADI had significant statistical correlations with the other questionnaires. Patients treated for head and neck cancer had a mean total score of 83 on the MDADI, which is indicative of minimal limitation in overall QOL. In conclusion, the present study validates the adaptation of the MDADI to the Brazilian Portuguese language and provides another tool to evaluate the impact of dysphagia on the QOL of head and neck cancer patients.


Therapeutic effects of kefir grain Lactobacillus-derived extracellular vesicles in mice with 2,4,6-trinitrobenzene sulfonic acid-induced inflammatory bowel disease.
Kefir is a fermented product from yeast and lactic acid bacteria, and has been associated with various health benefits including relieving inflammatory bowel disease. Recently, it has been shown that gram-positive bacteria produce extracellular vesicles (EV). The EV could be appearing as potentially important mediators of cell to cell interaction. In this study, we explored the role of kefir grain Lactobacillus-derived EV in modulating inflammation responses via alleviating the production of inflammatory cytokines in tumor necrosis factor-α (TNF-α)-induced inflammation in Caco-2 cells and the 2,4,6-trinitrobenzene sulfonic acid-induced inflammatory bowel disease mouse model. Kefir-derived Lactobacillus EV were isolated by ultracentrifugation of the culture medium of 3 different kefir-derived strains (i.e., Lactobacillus kefir, Lactobacillus kefiranofaciens, and Lactobacillus kefirgranum). Nanoparticle tracking analysis showed that the size of isolated kefir-derived Lactobacillus EV was within 80 to 400 nm, and kefir-derived Lactobacillus EV uptake into recipient Caco-2 cells was confirmed by fluorescence labeling. Treatment of each kefir-derived Lactobacillus EV onto TNF-α-stimulated Caco-2 cells significantly reduced the level of both mRNA expression and secretion of IL-8, and Western blot analysis revealed that such an effect was related to inhibition of TNF-α signaling mediated by reducing the phosphorylation of p65, a subunit of NF-kB. Subsequent administration of kefir-derived Lactobacillus EV into inflammatory bowel disease-induced mice significantly alleviated the body weight loss and rectal bleeding, and enhanced stool consistency. Histological examination showed that kefir-derived Lactobacillus EV substantially reduced the infiltration of transmural leukocytes and loss of goblet cells within the colon, and the serum level of myeloperoxidase was significantly lower in the EV-treated group than control group. Our study demonstrates that kefir-derived Lactobacillus EV can be potentially used for developing innovative strategies for alleviating inflammatory bowel disease.


What makes them split? Identifying risk factors that lead to monozygotic twins after in vitro fertilization.
To identify the incidence, risk factors, and obstetric/perinatal outcomes associated with monozygotic twins (MZTs) after IVF. Nested case-control. University-based center. The IVF cycles eventuating in pregnancy from 2000-2009. None. The MZT incidence, chorionicity/zygosity, pregnancy/neonatal outcome. Of 6,223 gestations, 131 MZTs were diagnosed (2.1% incidence; 2.0% in autologous and 2.7% in donor IVF cycles), 10 were dichorionic, and 121 were monochorionic. Controlling for all risk factors, young oocyte age, extended culture (noncleavage embryos transferred on/after day 4), and year of IVF treatment cycle were significantly associated with MZT. When assessing factors associated with specific MZT placentation, day 3 assisted hatching correlated more with dichorionic MZT, whereas extended culture and advanced day 5 embryonic stage correlated with monochorionic MZT. Comparing monozygotic to dizygotic multigestation outcomes, MZT fared worse; however, once controlling for triplet gestation, only gestational age at delivery remained significantly compromised in the monozygotic group. After IVF the incidence of MZT is high, with young oocyte age, year of treatment, and extended culture (or embryo stage at transfer) conferring greatest risk. Regarding MZT type, assisted reproductive technology (ART) procedures may influence the timing of embryonic splitting (i.e., division in early embryonic development may be influenced by zona pellucida [ZP] manipulation whereas later splitting may occur during delayed implantation). Poor obstetric/perinatal outcome is significantly impacted by the presence of an "extra" fetus, as high-order multiple gestation concurrent with an MZT conveyed the worst prognosis.


Arabidopsis thaliana germin-like proteins: common and specific features point to a variety of functions.
Germin-like proteins (GLPs) are ubiquitous plant proteins encoded by diverse multigene families. It is not known whether they share germin's unusual biochemical properties and oxalate oxidase activity. Using specific antibodies, we have studied three GLPs (AtGER1. AtGER2 and AtGER3) in Arabidopsis thaliana (L.) Heynh. as well as in transgenic tobacco (Nicotiana tabacum L.) plants overexpressing these proteins. Like wheat ( Triticum aestivum L.) germin, these Arabidopsis GLPs are associated with the extracellular matrix (ECM) and they also seem to exist as two glycosylated isoforms. However, none of them is an oxalate oxidase. Although GLPs display several conserved features, each has its specific characteristics. Both AtGER2 and AtGER3 are oligomeric proteins that share germin's resistance to pepsin and to dissociation by heat and SDS. In contrast, AtGER1 seems to exist as a monomer. The GLPs may interact with the ECM in a variety of ways, since each is efficiently extracted by different conditions. In addition, germins and GLPs all bind Cibacron Blue, a dye often but not exclusively used for the purification of enzymes having nucleotide cofactors. In the case of AtGER2, binding to the dye is so tight that it almost allows a one-step purification of this protein. The variety of sequences, expression patterns and biochemical features indicates that GLPs could be a class of receptors localized in the ECM and involved in physiological and developmental processes as well as stress response.


Five decades of missing females in China.
This paper seeks to explain the dearth of females in the population of China in cohorts born from the late 1930s to the present. We demonstrate that in virtually all cohorts, the shortage of females in comparison with males is revealed when the cohort is first enumerated in a census. Subsequently it barely changes, an indication that female losses occur very early in life. Using the high-quality data from the censuses and fertility surveys in China, we show that many of the births of the girls missing in the censuses were not reported in the surveys because they died very young. The incidence of excess early female mortality (probably infanticide) declined precipitously in the Communist period, but not to zero. The recent escalation in the proportion of young females missing in China has been caused largely by rapidly escalating sex-selective abortion.


The Cerebellar-Cerebral Microstructure Is Disrupted at Multiple Sites in Very Preterm Infants with Cerebellar Haemorrhage.
Recent advances in magnetic resonance imaging (MRI) techniques have prompted reconsideration of the anatomical correlates of adverse outcomes in preterm infants. The importance of the contribution made by the cerebellum is now increasingly appreciated. The effect of cerebellar haemorrhage (CBH) on the microstructure of the cerebellar-cerebral circuit is largely unexplored. To investigate the effect of CBH on the microstructure of cerebellar-cerebral connections in preterm infants aged <32 gestational weeks. Infants underwent diffusion tensor MRI at term-equivalent age. MRI was evaluated for CBH and additional supratentorial brain injury using a validated scoring system. Region of interest-based measures of brain microstructure (fractional anisotropy [FA] and apparent diffusion coefficient) were quantified in 5 vulnerable regions (the centrum semiovale, posterior limb of the internal capsule, corpus callosum, and superior and middle cerebellar peduncles). Group differences between infants with CBH and infants without CBH were assessed. There were 267 infants included in the study. Infants with CBH (isolated and combined) had significantly lower FA values in all regions investigated. Infants with isolated CBH showed lower FA in the middle and superior cerebellar peduncles and in the posterior limb of the internal capsule. This study provides evidence that CBH causes alterations in localised and remote WM pathways in the developing brain. The disruption of the cerebellar-cerebral microstructure at multiple sites adds further support for the concept of developmental diaschisis, which is propagated as an explanation for the consequences of early cerebellar injury on cognitive and affective domains.


2B, 2C, or 3: What Should Be the Angiographic Target for Endovascular Treatment in Ischemic Stroke?
Background and Purpose- A score of ≥2B on the modified Thrombolysis in Cerebral Infarction scale is generally regarded as successful reperfusion after endovascular treatment for ischemic stroke. The extended Thrombolysis in Cerebral Infarction (eTICI) includes a 2C grade, which indicates near-perfect reperfusion. We investigated how well the respective eTICI scores of 2B, 2C, and 3 correlate with clinical outcome after endovascular treatment. Methods- We used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry, a prospective, nationwide registry of endovascular treatment in the Netherlands. We included patients with a proximal intracranial occlusion of the anterior circulation for whom final antero-posterior and lateral digital subtraction angiography imaging was available. Our primary outcome was the distribution on the modified Rankin Scale at 90 days per eTICI grade. We performed (ordinal) logistic regression analyses, using eTICI 2B as reference group, and adjusted for potential confounders. Results- In total, 2807/3637 (77%) patients met the inclusion criteria. Of these, 17% achieved reperfusion grade eTICI 0 to 1, 14% eTICI 2A, 25% eTICI 2B, 12% eTICI 2C, and 32% eTICI 3. Groups differed in terms of age (P<0.001) and occlusion location (P<0.01). Procedure times decreased with increasing reperfusion grades. We found a positive association between reperfusion grade and functional outcome, which continued to increase after eTICI 2B (adjusted common odds ratio, 1.22 [95% CI, 0.96-1.57] for eTICI 2C versus 2B; adjusted common odds ratio, 1.33 [95% CI, 1.09-1.62] for eTICI 3 versus 2B). Conclusions- Our results indicate a continuous relationship between reperfusion grade and functional outcome, with eTICI 3 leading to the best outcomes. Although this implies that interventionists should aim for the highest possible reperfusion grade, further research on the optimal strategy is necessary.


East meets West: current practices and policies in the management of musculoskeletal aging.
Healthy aging is defined as the process of developing and maintaining the functional ability that enables wellbeing in older age. Healthy aging is dependent upon intrinsic capacity, a composite of physical and mental capacities, and the environment an individual inhabits and their interactions with it. Maintenance of musculoskeletal health during aging is a key determinant of functional ability. Sarcopenia, osteoporosis and osteoarthritis, are a triad of musculoskeletal diseases of aging that are major contributors to the global burden of disease and disability worldwide. The prevention and management of these disorders is of increasing importance with pressure mounting from the aging population. In a new initiative, the Chinese Medical Association, Chinese Society of Osteoporosis and Bone Mineral Research, and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases jointly organized a symposium to discuss current practices and policies in the management of musculoskeletal aging. The meeting allowed experts from Europe and China to share their experience and recommendations for the management of these three major diseases. Discussing and analyzing similarities and differences in their practice should lead, through a mutual enrichment of knowledge, to better management of these diseases, in order to preserve intrinsic capacity and retard the age-related degradation of physical ability. In future, it is hoped that sharing of knowledge and best practice will advance global strategies to reduce the burden of musculoskeletal disease and promote healthy aging tailored to meet the individual patient's needs.


Heterogeneity estimates in a biased world.
Meta-analyses typically quantify heterogeneity of results, thus providing information about the consistency of the investigated effect across studies. Numerous heterogeneity estimators have been devised. Past evaluations of their performance typically presumed lack of bias in the set of studies being meta-analysed, which is often unrealistic. The present study used computer simulations to evaluate five heterogeneity estimators under a range of research conditions broadly representative of meta-analyses in psychology, with the aim to assess the impact of biases in sets of primary studies on estimates of both mean effect size and heterogeneity in meta-analyses of continuous outcome measures. To this end, six orthogonal design factors were manipulated: Strength of publication bias; 1-tailed vs. 2-tailed publication bias; prevalence of p-hacking; true heterogeneity of the effect studied; true average size of the studied effect; and number of studies per meta-analysis. Our results showed that biases in sets of primary studies caused much greater problems for the estimation of effect size than for the estimation of heterogeneity. For the latter, estimation bias remained small or moderate under most circumstances. Effect size estimations remained virtually unaffected by the choice of heterogeneity estimator. For heterogeneity estimates, however, relevant differences emerged. For unbiased primary studies, the REML estimator and (to a lesser extent) the Paule-Mandel performed well in terms of bias and variance. In biased sets of primary studies however, the Paule-Mandel estimator performed poorly, whereas the DerSimonian-Laird estimator and (to a slightly lesser extent) the REML estimator performed well. The complexity of results notwithstanding, we suggest that the REML estimator remains a good choice for meta-analyses of continuous outcome measures across varied circumstances.


Midterm Follow-up of Divergent Peg Glenoid Components in Total Shoulder Arthroplasty.
Glenoid component aseptic loosening is the most common source of total shoulder arthroplasty (TSA) revision. Divergent pegged glenoids may improve fixation. Thirty-four patients underwent divergent peg TSA. Data were reviewed for component loosening. Failure was defined as the need for revision after loosening. The last postoperative radiographs were graded on a Lazarus glenoid lucency scale. Mean follow-up was 5.6 years ± 2.44 (range, 2-10 years). Radiolucency around one or fewer pegs was noted in 14/20 patients. Six glenoids had complete radiolucency around two pegs; one shoulder had gross loosening. No secondary surgery was performed. Improvements were seen in active elevation and internal rotation. The mean Shoulder Pain and Disability Index (SPADI) score decreased by 48.1 points (p = .039). Shoulder elevation, internal rotation, and SPADI scores significantly improved at final follow-up. No patients underwent revision for glenoid loosening. There were, however, a significant number of patients with radiolucency around two pegs. (Journal of Surgical Orthopaedic Advances 27(1):6-9, 2018).


Clinical associations of the metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort.
The metabolic syndrome (MetS) may contribute to increased cardiovascular risk in systemic lupus erythematosus (SLE). We aimed to examine the association of demographic factors, lupus phenotype and therapy exposure with the presence of MetS. The Systemic Lupus International Collaborating Clinics Registry for Atherosclerosis inception cohort enrolled recently diagnosed (<15 months) SLE patients from 30 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected according to a standardised protocol. MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Univariate and backward stepwise multivariate logistic regression were used to assess the relationship of individual variables with MetS. We studied 1686 patients, of whom 1494 (86.6%) had sufficient data to determine their MetS status. The mean (SD) age at enrolment and disease duration was 35.2 years (13.4) and 24.1 weeks (18.0), respectively. MetS was present at the enrolment visit in 239 (16%). In backward stepwise multivariable regression analysis, higher daily average prednisolone dose (mg) (OR 1.02, 95% CI 1.00 to 1.03), older age (years) (OR 1.04, 95% CI 1.03 to 1.06), Korean (OR 6.33, 95% CI 3.68 to 10.86) and Hispanic (OR 6.2, 95% CI 3.78 to 10.12) ethnicity, current renal disease (OR 1.79, 95% CI 1.14 to 2.80) and immunosuppressant use (OR 1.81, 95% CI 1.18 to 2.78) were associated with MetS. Renal lupus, higher corticosteroid doses, Korean and Hispanic ethnicity are associated with MetS in SLE patients. Balancing disease control and minimising corticosteroid exposure should therefore be at the forefront of personalised treatment decisions in SLE patients.


Humoral immune response against two surface antigens of Chlamydia pecorum in vaccinated and naturally infected sheep.
Chlamydia pecorum is a globally recognised livestock pathogen due to the significant clinical and economic impact it poses to livestock producers. Routine serological diagnosis is through a complement fixation test (CFT), which is often criticised for cross-reactivity, poor sensitivity and specificity. Although serology remains the preferred method in veterinary diagnostic laboratories, serological assays based on surface antigens of C. pecorum have not been established until now. In this study, we evaluated the use of two chlamydial recombinant protein antigens (PmpG and MOMP-G) by a direct IgG ELISA method for detection of ovine anti-chlamydial antibodies. Using the Pepscan method we then identified B cell epitopes across PmpG and MOMP-G proteins, in lambs with (a) naturally occurring asymptomatic C. pecorum infections (b) C. pecorum-associated polyarthritis and (c) recombinant PmpG and MOMP-G vaccine. Plasma IgG antibodies to PmpG in natural infection of lambs were detected earlier in infection than CFT and served as an acute phase marker. Antibodies to MOMP-G IgG were significantly heightened in lambs with C. pecorum-associated polyarthritis. PmpG and MOMP-G specific B-cell epitope mapping revealed epitope responses in immunised lambs cluster with some of the epitope responses in naturally infected lambs. B-cell epitope mapping further revealed that lambs with polyarthritis recognised several unique PmpG (50% frequency, peptide 8, 25, 40, 41 and 50) and MOMP (50% frequency, peptide 50) epitopes in comparison to asymptomatic infections. The findings of this study will have implications towards improved serodiagnosis of C. pecorum infections in livestock and inform the downstream development of alternative peptide-based antigens for future C. pecorum vaccine studies.


Operative endoscopy of the airway.
Airway endoscopy has long been an important and useful tool in the management of thoracic diseases. As thoracic specialists have gained experience with both flexible and rigid bronchoscopic techniques, the technology has continued to evolve so that bronchoscopy is currently the foundation for diagnosis and treatment of many thoracic ailments. Airway endoscopy plays a significant role in the biopsy of tumors within the airways, mediastinum, and lung parenchyma. Endoscopic methods have been developed to treat benign and malignant airway stenoses and tracheomalacia. And more recently, techniques have been conceived to treat end-stage emphysema and prolonged air leaks in select patients. This review describes the abundant uses of airway endoscopy, as well as technical considerations and limitations of the current technologies.


Rheostatic control of tryptic digestion in a microscale fluidic system.
Integrated fluidic systems that unite bottom-up and top-down proteomic approaches have the potential to deliver complete protein characterization. To circumvent fraction collection, as is conducted in current blended approaches, a technique to regulate digestion efficiency in a flow-through system is required. The present study examined the concept of regulating tryptic digestion in an immobilized enzyme reactor (IMER), incorporating mixed solvent systems for digestion acceleration. Using ovalbumin, cytochrome c, and myoglobin as protein standards, we demonstrate that tryptic digestion can be efficiently regulated between complete digestion and no digestion extremes by oscillating between 45 and 0% acetonitrile in the fluid stream. Solvent composition was tuned using programmable solvent waveforms in a closed system consisting of the IMER, a sample delivery stream, a dual gradient pumping system and a mass spectrometer. Operation in this rheostatic digestion mode provides access to novel peptide mass maps (due to substrate unfolding hysteresis) as well as the intact protein, in a reproducible and stable fashion. Although cycle times were on the order of 90 s for testing purposes, we show that regulated digestion is sufficiently rapid to be limited by solvent switching efficiency and kinetics of substrate unfolding/folding. Thus, regulated digestion should be useful in blending bottom-up and top-down proteomics in a single closed fluidic system.


Garlic and onions: their cancer prevention properties.
The Allium genus includes garlic, onions, shallots, leeks, and chives. These vegetables are popular in cuisines worldwide and are valued for their potential medicinal properties. Epidemiologic studies, while limited in their abilities to assess Allium consumption, indicate some associations of Allium vegetable consumption with decreased risk of cancer, particularly cancers of the gastrointestinal tract. Limited intervention studies have been conducted to support these associations. The majority of supportive evidence on Allium vegetables cancer-preventive effects comes from mechanistic studies. These studies highlight potential mechanisms of individual sulfur-containing compounds and of various preparations and extracts of these vegetables, including decreased bioactivation of carcinogens, antimicrobial activities, and redox modification. Allium vegetables and their components have effects at each stage of carcinogenesis and affect many biologic processes that modify cancer risk. This review discusses the cancer-preventive effects of Allium vegetables, particularly garlic and onions, and their bioactive sulfur compounds and highlights research gaps.


Auxin transport and stem vascular reconnection - has our thinking become canalized?
The presence of a polar auxin transport stream has long been correlated with the differentiation and patterning of vascular cells across vascular plants. As our understanding of auxin transport and vascular development has grown, so too has evidence for the correlation between these processes. However, a clear understanding of the cellular and molecular mechanisms driving this correlation has not been elucidated. This article examines the hypothesis that canalization via polar auxin transport regulates vascular reconnection and patterning in the stem after wounding or grafting. We examine the evidence for the causal nature of the relationship and the suggested role that other hormones may play. Data are presented indicating that in grafted plants the degree of auxin transport may not always correlate with vascular reconnection. Furthermore, data on grafting success using plants with a range of hormone-related mutations indicate that these hormones may not be critical for vascular reconnection. In the past, excellent work examining elements of auxin synthesis, transport and response in relation to vascular development has been carried out. However, new experimental approaches are required to test more directly the hypothesis that auxin transport regulates stem vascular reconnection after wounding or grafting. This could include studies on the timing of the re-establishment of auxin transport and vascular reconnection after grafting and the influence of auxin transport mutants and inhibitors on these processes using live imaging.


Single molecule high-throughput footprinting of small and large DNA ligands.
Most DNA processes are governed by molecular interactions that take place in a sequence-specific manner. Determining the sequence selectivity of DNA ligands is still a challenge, particularly for small drugs where labeling or sequencing methods do not perform well. Here, we present a fast and accurate method based on parallelized single molecule magnetic tweezers to detect the sequence selectivity and characterize the thermodynamics and kinetics of binding in a single assay. Mechanical manipulation of DNA hairpins with an engineered sequence is used to detect ligand binding as blocking events during DNA unzipping, allowing determination of ligand selectivity both for small drugs and large proteins with nearly base-pair resolution in an unbiased fashion. The assay allows investigation of subtle details such as the effect of flanking sequences or binding cooperativity. Unzipping assays on hairpin substrates with an optimized flat free energy landscape containing all binding motifs allows determination of the ligand mechanical footprint, recognition site, and binding orientation.Mapping the sequence specificity of DNA ligands remains a challenge, particularly for small drugs. Here the authors develop a parallelized single molecule magnetic tweezers approach using engineered DNA hairpins that can detect sequence selectivity, thermodynamics and kinetics of binding for small drugs and large proteins.


Knocking the NT4 gene into the BDNF locus rescues BDNF deficient mice and reveals distinct NT4 and BDNF activities.
To directly compare biological activities of the neurotrophins NT4 and BDNF in vivo, we replaced the BDNF coding sequence with the NT4 sequence in mice (Bdnfnt4-ki). Mice expressing NT4 in place of BDNF were viable, in contrast with BDNF null mutants, which die shortly after birth. Although the Bdnfnt4-ki/nt4-ki and wild-type Bdnf+/+ alleles yielded similar levels of NT4 and BDNF proteins, NT4 supported more sensory neurons than BDNF and promoted functional synapse formation in cultured hippocampal neurons. Homozygous Bdnfnt4-ki/nt4-ki mice showed reduced body weight, infertility and skin lesions, suggesting unique biological activities of NT4 in vivo. The distinct activities of NT4 and BDNF may result partly from differential activation of the TrkB receptor and its down-stream signals.


Range-wide genetic analysis of Dermacentor variabilis and its Francisella-like endosymbionts demonstrates phylogeographic concordance between both taxa.
The American dog tick, Dermacentor variabilis, is an important vector of pathogens to humans, wildlife and domestic animals in North America. Although this tick species is widely distributed in the USA and Canada, knowledge of its range-wide phylogeographic patterns remains incomplete. We carried out a phylogenetic analysis of D. variabilis using samples collected from 26 USA states and five Canadian provinces. Tick samples (n = 1053 in total) originated from two main sources: existing archives (2000-2011), and new collections made from 2012 to 2013. We sequenced a 691 bp fragment of the cox1 gene from a subset (n = 332) of geographically diverse D. variabilis. DNA extracted from individual ticks (n = 1053) was also screened for a Francisella-like endosymbiont, using a targeted 16S rRNA sequencing approach, and important pathogens (Rickettsia spp. and Coxiella burnetii), using species-specific quantitative PCR assays. Maximum parsimony analysis of cox1 sequences revealed two major groups within D. variabilis with distinct geographical distributions: one from the eastern USA/Canada (Group 1) and one from the west coast states of the USA (California and Washington; Group 2). However, genetic subdivisions within both of these two major groups were weak to moderate and not tightly correlated with geography. We found molecular signatures consistent with Francisella-like endosymbionts in 257 of the DNA extracts from the 1053 individual ticks, as well as Rickettsia spp. and Coxiella burnetii in a small number of ticks (n = 29 and 2, respectively). Phylogenetic patterns for Francisella-like endosymbionts, constructed using sequence data from the bacterial 16S rRNA locus, were similar to those for D. variabilis, with two major groups that had a nearly perfect one-to-one correlation with the two major groups within D. variabilis. Our findings reveal a distinct phylogenetic split between the two major D. variabilis populations. However, high levels of genetic mixture among widely separated geographical localities occur within each of these two major groups. Furthermore, our phylogenetic analyses provide evidence of long-term tick-symbiont co-evolution. This work has implications for understanding the dispersal and evolutionary ecology of D. variabilis and associated vector-borne diseases.


Comparative Genomics and Identification of an Enterotoxin-Bearing Pathogenicity Island, SEPI-1/SECI-1, in Staphylococcus epidermidis Pathogenic Strains.
Staphylococcus epidermidis is a leading cause of nosocomial infections, majorly resistant to beta-lactam antibiotics, and may transfer several mobile genetic elements among the members of its own species, as well as to Staphylococcus aureus; however, a genetic exchange from S. aureus to S. epidermidis remains controversial. We recently identified two pathogenic clinical strains of S. epidermidis that produce a staphylococcal enterotoxin C3-like (SEC) similar to that by S. aureus pathogenicity islands. This study aimed to determine the genetic environment of the SEC-coding sequence and to identify the mobile genetic elements. Whole-genome sequencing and annotation of the S. epidermidis strains were performed using Illumina technology and a bioinformatics pipeline for assembly, which provided evidence that the SEC-coding sequences were located in a composite pathogenicity island that was previously described in the S. epidermidis strain FRI909, called SePI-1/SeCI-1, with 83.8-89.7% nucleotide similarity. Various other plasmids were identified, particularly p_3_95 and p_4_95, which carry antibiotic resistance genes (hsrA and dfrG, respectively), and share homologies with SAP085A and pUSA04-2-SUR11, two plasmids described in S. aureus. Eventually, one complete prophage was identified, ΦSE90, sharing 30 out of 52 coding sequences with the Acinetobacter phage vB_AbaM_IME200. Thus, the SePI-1/SeCI-1 pathogenicity island was identified in two pathogenic strains of S. epidermidis that produced a SEC enterotoxin causing septic shock. These findings suggest the existence of in vivo genetic exchange from S. aureus to S. epidermidis.


RanBP2/Nup358 provides a major binding site for NXF1-p15 dimers at the nuclear pore complex and functions in nuclear mRNA export.
Metazoan NXF1-p15 heterodimers promote the nuclear export of bulk mRNA across nuclear pore complexes (NPCs). In vitro, NXF1-p15 forms a stable complex with the nucleoporin RanBP2/Nup358, a component of the cytoplasmic filaments of the NPC, suggesting a role for this nucleoporin in mRNA export. We show that depletion of RanBP2 from Drosophila cells inhibits proliferation and mRNA export. Concomitantly, the localization of NXF1 at the NPC is strongly reduced and a significant fraction of this normally nuclear protein is detected in the cytoplasm. Under the same conditions, the steady-state subcellular localization of other nuclear or cytoplasmic proteins and CRM1-mediated protein export are not detectably affected, indicating that the release of NXF1 into the cytoplasm and the inhibition of mRNA export are not due to a general defect in NPC function. The specific role of RanBP2 in the recruitment of NXF1 to the NPC is highlighted by the observation that depletion of CAN/Nup214 also inhibits cell proliferation and mRNA export but does not affect NXF1 localization. Our results indicate that RanBP2 provides a major binding site for NXF1 at the cytoplasmic filaments of the NPC, thereby restricting its diffusion in the cytoplasm after NPC translocation. In RanBP2-depleted cells, NXF1 diffuses freely through the cytoplasm. Consequently, the nuclear levels of the protein decrease and export of bulk mRNA is impaired.


Hemodynamic instability during treatment of intracranial dural arteriovenous fistula and carotid cavernous fistula with Onyx: preliminary results and anesthesia considerations.
9 patients with 10 arteriovenous fistulas were treated with Onyx at our institution over a period of 19 months: 4 direct and indirect carotid-cavernous fistulas (CCFs) and 6 dural arteriovenous fistula (DAVFs). Complete occlusion was achieved with no recurrences or permanent complications in our small series. We report hemodynamic instability, including severe bradycardia and asystole, during embolization of DAVF and CCF with Onyx in several patients. These changes were reversible with interruption of Onyx injection and administration of atropine. No recurrence of symptoms after atropine administration was noted as Onyx embolization continued during the same session or during postprocedural 24 h monitoring. No adverse clinical consequences were noted. Bradycardia was observed in 4 cases, with a brief asystole in 2 of these patients during transarterial and transvenous Onyx delivery at cavernous sinus and orbital levels. Based on our observation, hemodynamic instability was demonstrated during Onyx injection into the vessels that were in close proximity to the trigeminal nerve or its branches, especially in low-flow/low-volume compartment and may represent a direct effect of dimethyl sulfoxide/Onyx on the trigeminal nerve, resulting in vagal response from trigeminocardiac reflex. Proposed measures to prevent this complication include pretreatment with atropine or prophylactic placement of transvenous pacemakers in patients with underlying heart block and patients with contraindications to atropine use.


Minimally invasive Oxford unicompartmental knee arthroplasty: functional results at 1 year and the effect of surgical inexperience.
Oxford medial unicompartmental arthroplasty (UCA) is now routinely performed through a short incision without dislocation of the patella. We present the 1 year results of the first 104 knees operated in Oxford using this technique and the learning curve associated with it. The patient's average age at surgery was 68 years. The average American Knee Society 'knee score' improved from 37 to 94 points and the average 'functional score' from 50 to 92 points. Average maximum flexion improved from 117 to 131 degrees. The average knee score during a surgeon's first 10 cases was 88 points, which was significantly less (P<0.03) than the score achieved for subsequent cases after the first 10 (95 points). These data suggest for the first time that a learning curve exists with worse results being achieved during a surgeon's first 10 cases. However, the results during the learning curve are still similar to that achieved after total knee arthroplasty.


Affinity maturation generates greatly improved xyloglucan-specific carbohydrate binding modules.
Molecular evolution of carbohydrate binding modules (CBM) is a new approach for the generation of glycan-specific molecular probes. To date, the possibility of performing affinity maturation on CBM has not been investigated. In this study we show that binding characteristics such as affinity can be improved for CBM generated from the CBM4-2 scaffold by using random mutagenesis in combination with phage display technology. Two modified proteins with greatly improved affinity for xyloglucan, a key polysaccharide abundant in the plant kingdom crucial for providing plant support, were generated. Both improved modules differ from other existing xyloglucan probes by binding to galactose-decorated subunits of xyloglucan. The usefulness of the evolved binders was verified by staining of plant sections, where they performed better than the xyloglucan-binding module from which they had been derived. They discriminated non-fucosylated from fucosylated xyloglucan as shown by their ability to stain only the endosperm, rich in non-fucosylated xyloglucan, but not the integument rich in fucosylated xyloglucan, on tamarind seed sections. We conclude that affinity maturation of CBM selected from molecular libraries based on the CBM4-2 scaffold is possible and has the potential to generate new analytical tools for detection of plant carbohydrates.


Spexin-Based Galanin Receptor Type 2 Agonist for Comorbid Mood Disorders and Abnormal Body Weight.
Despite the established comorbidity between mood disorders and abnormal eating behaviors, the underlying molecular mechanism and therapeutics remain to be resolved. Here, we show that a spexin-based galanin receptor type 2 agonist (SG2A) simultaneously normalized mood behaviors and body weight in corticosterone pellet-implanted (CORTI) mice, which are underweight and exhibit signs of anhedonia, increased anxiety, and depression. Administration of SG2A into the lateral ventricle produced antidepressive and anxiolytic effects in CORTI mice. Additionally, SG2A led to a recovery of body weight in CORTI mice while it induced significant weight loss in normal mice. In Pavlovian fear-conditioned mice, SG2A decreased contextual and auditory fear memory consolidation but accelerated the extinction of acquired fear memory without altering innate fear and recognition memory. The main action sites of SG2A in the brain may include serotonergic neurons in the dorsal raphe nucleus for mood control, and proopiomelanocortin/corticotropin-releasing hormone neurons in the hypothalamus for appetite and body weight control. Furthermore, intranasal administration of SG2A exerted the same anxiolytic and antidepressant-like effects and decreased food intake and body weight in a dose-dependent manner. Altogether, these results indicate that SG2A holds promise as a clinical treatment for patients with comorbid mood disorders and abnormal appetite/body weight.


Low calcium intake is related to increased risk of tooth loss in men.
Our aim was to investigate the association between calcium (Ca) intake and number of teeth and tooth loss. The Danish Monica (Monitoring Trends and Determinants in Cardiovascular Disease) study is a prospective observational study from 1982-83 to 1993-94. The study population included 1602 adults (30-60 y) with information on dietary Ca intake and number of teeth and a subset of 511 participants with information on tooth loss from 1987-88 to 1993-94. Ca intake less than the recommendations, estimated by a 7-d food record or a diet history interview in 1982-83, was more frequent among females (55%) than males (45%; P < 0.001). Low Ca intake was associated with low number of teeth (1-25 vs. 26-32 teeth) in males [odds ratio (OR) = 1.57 (95% CI = 1.10-2.29)] and females [OR = 1.44 (95% CI = 1.10-2.05)] after adjustment for age, education, smoking, alcohol and sucrose consumption, subjective oral dryness, and time since last dental care visit. The reference group (26-32 teeth) and edentulous participants did not significantly differ. A Ca intake below recommendations was significantly associated with increased risk of subsequent tooth loss in males [incidence-rate ratio = 1.70 (95% CI = 1.15-2.48)]. There was no association in women. Ca intake below recommendations was significantly associated with fewer teeth in both sexes. However, there was a significant, negative association between Ca intake below recommendations and tooth loss in males only. Given the high percentage of individuals with Ca intake below recommendations, consumption of foods rich in Ca should be promoted to preserve oral health.


Variations in composition of dietary fats affect hepatic uptake and metabolism of chylomicron remnants.
The hepatic metabolism of [1-14C]oleate- and [1,2-3H]cholesterol-dual-labelled chylomicron remnants derived from olive, corn, palm and fish oil and butter fat was compared by adding each lipoprotein separately to the perfusate of isolated livers from rats fed on a normal diet. Labelled remnants from butter fat and fish oil were removed more rapidly from the perfusate than remnants derived from olive, corn and palm oil. The oxidation of labelled remnant fatty acid from olive oil, fish oil or butter fat was four to seven times greater than that from corn and palm oil. Labelled fatty acid in fish oil remnants was incorporated into phospholipid significantly more efficiently than the labelled fatty acid in olive, corn or palm oil remnants, with butter fat giving an intermediate value. For all the remnants, there was a significant amount of hydrolysis of labelled esterified cholesterol by the liver which was dependent on the magnitude of hepatic uptake of each type of remnant. The recovery of remnant [3H]cholesterol label in the bile was 50% less with palm oil remnants than with all the other remnants studied. The results indicate that the fatty acid composition of chylomicron remnants has a major impact on their uptake and metabolism by the liver.


Increased theta/alpha synchrony in the habenula-prefrontal network with negative emotional stimuli in human patients.
Lateral habenula is believed to encode negative motivational stimuli and plays key roles in the pathophysiology of psychiatric disorders. However, how habenula activities are modulated during the processing of emotional information is still poorly understood. We recorded local field potentials from bilateral habenula areas with simultaneous cortical magnetoencephalography in nine patients with psychiatric disorders during an emotional picture-viewing task. Transient activity in the theta/alpha band (5-10 Hz) within the habenula and prefrontal cortical regions, as well as the coupling between these structures, is increased during the perception and processing of negative emotional stimuli compared to positive emotional stimuli. The increase in theta/alpha band synchronization in the frontal cortex-habenula network correlated with the emotional valence but not the arousal score of the stimuli. These results provide direct evidence for increased theta/alpha synchrony within the habenula area and prefrontal cortex-habenula network in the perception of negative emotion in human participants.


In a demanding task, three-handed manipulation is preferred to two-handed manipulation.
Equipped with a third hand under their direct control, surgeons may be able to perform certain surgical interventions alone; this would reduce the need for a human assistant and related coordination difficulties. However, does human performance improve with three hands compared to two hands? To evaluate this possibility, we carried out a behavioural study on the performance of naive adults catching objects with three virtual hands controlled by their two hands and right foot. The subjects could successfully control the virtual hands in a few trials. With this control strategy, the workspace of the hands was inversely correlated with the task velocity. The comparison of performance between the three and two hands control revealed no significant difference of success in catching falling objects and in average effort during the tasks. Subjects preferred the three handed control strategy, found it easier, with less physical and mental burden. Although the coordination of the foot with the natural hands increased trial after trial, about two minutes of practice was not sufficient to develop a sense of ownership towards the third arm.


False negative results from using common PCR reagents.
The sensitivity of the PCR reaction makes it ideal for use when identifying potentially novel viral infections in human disease. Unfortunately, this same sensitivity also leaves this popular technique open to potential contamination with previously amplified PCR products, or "carry-over" contamination. PCR product carry-over contamination can be prevented with uracil-DNA-glycosylase (UNG), and it is for this reason that it is commonly included in many commercial PCR master-mixes. While testing the sensitivity of PCR assays to detect murine DNA contamination in human tissue samples, we inadvertently discovered that the use of this common PCR reagent may lead to the production of false-negative PCR results. We show here that contamination with minute quantities of UNG-digested PCR product or any negative control PCR reactions containing primer-dimers regardless of UNG presence can completely block amplification from as much as 60 ng of legitimate target DNA. These findings could potentially explain discrepant results from laboratories attempting to amplify MLV-related viruses including XMRV from human samples, as none of the published reports used internal-tube controls for amplification. The potential for false negative results needs to be considered and carefully controlled in PCR experiments, especially when the target copy number may be low - just as the potential for false positive results already is.


Fourfold Filtered Statistical/Computational Approach for the Identification of Imidazole Compounds as HO-1 Inhibitors from Natural Products.
Over-regulation of Heme oxygenase 1 (HO-1) has been recently identified in many types of human cancer, and in these cases, poor clinical outcomes are normally reported. Indeed, the inhibition of HO-1 is being considered as an anticancer approach. Imidazole scaffold is normally present in most of the classical HO-1 inhibitors and seems indispensable to the inhibitory activity due to its strong interaction with the Fe(II) of the heme group. In this paper, we searched for new potentially HO-1 inhibitors among three different databases: Marine Natural Products (MNP), ZINC Natural Products (ZNP) and Super Natural II (SN2). 484,527 compounds were retrieved from the databases and filtered through four statistical/computational filters (2D descriptors, 2D-QSAR pharmacophoric model, 3D-QSAR pharmacophoric model, and docking). Different imidazole-based compounds were suggested by our methodology to be potentially active in inhibiting the HO-1, and the results have been rationalized by the bioactivity of the filtered molecules reported in the literature.


Sparse incomplete representations: a potential role of olfactory granule cells.
Mitral/tufted cells of the olfactory bulb receive odorant information from receptor neurons and transmit this information to the cortex. Studies in awake behaving animals have found that sustained responses of mitral cells to odorants are rare, suggesting sparse combinatorial representation of the odorants. Careful alignment of mitral cell firing with the phase of the respiration cycle revealed brief transient activity in the larger population of mitral cells, which respond to odorants during a small fraction of the respiration cycle. Responses of these cells are therefore temporally sparse. Here, we propose a mathematical model for the olfactory bulb network that can reproduce both combinatorially and temporally sparse mitral cell codes. We argue that sparse codes emerge as a result of the balance between mitral cells' excitatory inputs and inhibition provided by the granule cells. Our model suggests functional significance for the dendrodendritic synapses mediating interactions between mitral and granule cells.


Hybrid sterility, Haldane's rule and speciation in Heliconius cydno and H. melpomene.
Most genetic studies of Haldane's rule, in which hybrid sterility or inviability affects the heterogametic sex preferentially, have focused on Drosophila. It therefore remains unclear to what extent the conclusions of that work apply more generally, particularly in female-heterogametic taxa such as birds and Lepidoptera. Here we present a genetic analysis of Haldane's rule in Heliconius butterflies. Female F(1) hybrids between Heliconius melpomene and H. cydno are completely sterile, while males have normal to mildly reduced fertility. In backcrosses of male F(1) hybrids, female offspring range from completely sterile to fully fertile. Linkage analysis using the Z-linked triose-phosphate isomerase locus demonstrates a "large X" (Z) effect on sterility. Expression of female sterility varies among crosses in this and a previous study of Heliconius. Sterility may result from the production of normal but infertile eggs, production of small infertile eggs, or from a complete failure to develop ovarioles, which suggests multiple routes to the evolution of hybrid sterility in these Heliconius species. These results conform to the expectations of the "dominance" rather than "faster male" theories of Haldane's rule and suggest that relatively few loci are responsible. The two species are broadly sympatric and hybridize in the wild, so that female hybrid sterility forms one of several strong but incomplete barriers to gene flow in nature. The effect of female sterility is comparable to that of selection against non-mimetic hybrids, while mate choice forms a much stronger barrier to gene transfer.


Vitamin A supplementation in northern Ghana: effects on clinic attendances, hospital admissions, and child mortality. Ghana VAST Study Team.
Although most studies on the effect of vitamin A supplementation have reported reductions in childhood mortality, the effects on morbidity are less clear. We have carried out two double-blind, randomised, placebo-controlled trials of vitamin A supplementation in adjacent populations in northern Ghana to assess the impact on childhood morbidity and mortality. The Survival Study included 21,906 children aged 6-90 months in 185 geographical clusters, who were followed for up to 26 months. The Health Study included 1455 children aged 6-59 months, who were monitored weekly for a year. Children were randomly assigned either 200,000 IU retinol equivalent (100,000 IU under 12 months) or placebo every 4 months; randomisation was by individual in the Health Study and by cluster in the Survival Study. There were no significant differences in the Health Study between the vitamin A and placebo groups in the prevalence of diarrhoea or acute respiratory infections; of the symptoms and conditions specifically asked about, only vomiting and anorexia were significantly less frequent in the supplemented children. Vitamin-A-supplemented children had significantly fewer attendances at clinics (rate ratio 0.88 [95% CI 0.81-0.95], p = 0.001), hospital admissions (0.62 [0.42-0.93], p = 0.02), and deaths (0.81 [0.68-0.98], p = 0.03) than children who received placebo. The extent of the effect on morbidity and mortality did not vary significantly with age or sex. However, the mortality rate due to acute gastroenteritis was lower in vitamin-A-supplemented than in placebo clusters (0.66 [0.47-0.92], p = 0.02); mortality rates for all other causes except acute lower respiratory infections and malaria were also lower in vitamin A clusters, but not significantly so. Improving the vitamin A intake of young children in populations where xerophthalmia exists, even at relatively low prevalence, should be a high priority for health and agricultural services in Africa and elsewhere.


Prion protein NMR structure from tammar wallaby (Macropus eugenii) shows that the beta2-alpha2 loop is modulated by long-range sequence effects.
NMR structures are presented for the recombinant construct of residues 121-230 from the tammar wallaby (Macropus eugenii) prion protein (PrP) twPrP(121-230) and for the variant mouse PrPs mPrP[Y225A,Y226A](121-231) and mPrP[V166A](121-231) at 20 degrees C and pH 4.5. All three proteins exhibit the same global architecture as seen in other recombinant PrP(C)s (cellular isoforms of PrP) and shown to prevail in natural bovine PrP(C). Special interest was focused on a loop that connects the beta2-strand with helix alpha2 in the PrP(C) fold, since there are indications from in vivo experiments that this local structural feature affects the susceptibility of transgenic mice to transmissible spongiform encephalopathies. This beta2-alpha2 loop and helix alpha3 form a solvent-accessible contiguous epitope, which has been proposed to be the recognition area for a hypothetical chaperone, the "protein X". This hypothetical chaperone would affect the conversion of PrP(C) into the disease-related scrapie form (PrP(Sc)) by moderating intermolecular interactions related to the transmission barrier of transmissible spongiform encephalopathies between different species. In contrast to mPrP(121-231) and most other mammalian PrP(C)s, the beta2-alpha2 loop is well defined at 20 degrees C in tammar wallaby PrP and in the two aforementioned variants of mPrP, showing that long-range interactions with helix alpha3 can have an overriding influence on the structural definition of the beta2-alpha2 loop. Further NMR studies with two variant mPrPs, mPrP[Y225A](121-231) and mPrP[Y226A](121-231), showed that these interactions are dominantly mediated by close contacts between residues 166 and 225. The results of the present study then lead to the intriguing indication that well-defined long-range intramolecular interactions could act as regulators of the functional specificity of PrP(C).


The effect of group involvement on post-disaster mental health: A longitudinal multilevel analysis.
Involvement in voluntary associations is a key form of social capital and plays an especially important role following disaster as a venue for coordination and decision-making for the wider community. Yet, relatively little attention has been paid to how group involvement affects mental health, at either the individual or community level. The aim of this study was to assess the impact of involvement in voluntary associations on mental health among residents of bushfire-affected communities. A longitudinal sample of 642 individuals affected by the 2009 Victorian bushfires in south-eastern Australia were surveyed in 2012 and 2014 (3- and 5-years post-disaster). A further subsample (n = 552) of residents residing continuously within 22 bushfire-affected communities were examined for community-level effects using multilevel regression methods. After adjusting for demographics, disaster exposure, and network variables, group involvement at time 1 bore a curvilinear relationship with PTSD at both time points: moderate involvement was most beneficial, with no participation, or high amounts, yielding poorer outcomes. High amounts of group involvement was likewise linked to a greater risk of major depression. Furthermore, communities with higher median levels of group involvement reported lower levels of PTSD symptoms and major depression two years later. With respect to group involvement, more is not always better. For individuals, moderation - if possible - is key. Meanwhile, community-level health benefits come when most people participate to some extent, suggesting that the distribution of involvement across the community is important.


Differences in Femoral Torsion Among Various Measurement Methods Increase in Hips With Excessive Femoral Torsion.
Correct quantification of femoral torsion is crucial to diagnose torsional deformities, make an indication for surgical treatment, or plan the amount of correction. However, no clear evaluation of different femoral torsion measurement methods for hips with excessive torsion has been performed to date. (1) How does CT-based measurement of femoral torsion differ among five commonly used measurement methods? (2) Do differences in femoral torsion among measurement methods increase in hips with excessive femoral torsion? (3) What is the reliability and reproducibility of each of the five torsion measurement methods? Between March and August 2016, we saw 86 new patients (95 hips) with hip pain and physical findings suggestive for femoroacetabular impingement at our outpatient tertiary clinic. Of those, 56 patients (62 hips) had a pelvic CT scan including the distal femur for measurement of femoral torsion. We excluded seven patients (seven hips) with previous hip surgery, two patients (two hips) with sequelae of Legg-Calvé-Perthes disease, and one patient (one hip) with a posttraumatic deformity. This resulted in 46 patients (52 hips) in the final study group with a mean age of 28 ± 9 years (range, 17-51 years) and 27 female patients (59%). Torsion was compared among five commonly used assessment measures, those of Lee et al., Reikerås et al., Jarrett et al., Tomczak et al., and Murphy et al. They differed regarding the level of the anatomic landmark for the proximal femoral neck axis; the method of Lee had the most proximal definition followed by the methods of Reikerås, Jarrett, and Tomczak at the base of the femoral neck and the method of Murphy with the most distal definition at the level of the lesser trochanter. The definition of the femoral head center and of the distal reference was consistent for all five measurement methods. We used the method described by Murphy et al. as our baseline measurement method for femoral torsion because it reportedly most closely reflects true anatomic femoral torsion. With this method we found a mean femoral torsion of 28 ± 13°. Mean values of femoral torsion were compared among the five methods using multivariate analysis of variance. All differences between two of the measurement methods were plotted over the entire range of femoral torsion to evaluate a possible increase in hips with excessive femoral torsion. All measurements were performed by two blinded orthopaedic residents (FS, TDL) at two different occasions to measure intraobserver reproducibility and interobserver reliability using intraclass correlation coefficients (ICCs). We found increasing values for femoral torsion using measurement methods with a more distal definition of the proximal femoral neck axis: Lee et al. (most proximal definition: 11° ± 11°), Reikerås et al. (15° ± 11°), Jarrett et al. (19° ± 11°), Tomczak et al. (25° ± 12°), and Murphy et al. (most distal definition: 28° ± 13°). The most pronounced difference was found for the comparison between the methods of Lee et al. and Murphy et al. with a mean difference of 17° ± 5° (95% confidence interval, 16°-19°; p < 0.001). For six of 10 possible pairwise comparisons, the difference between two methods increased with increasing femoral torsion and decreased with decreasing femoral torsion. We observed a fair-to-strong linear correlation (R range, 0.306-0.622; all p values < 0.05) for any method compared with the Murphy method and for the Reikerås and Jarrett methods when compared with the Tomczak method. For example, a hip with 10° of femoral antetorsion according Murphy had a torsion of 1° according to Reikerås, which corresponds to a difference of 9°. This difference increased to 20° in hips with excessive torsion; for example, a hip with 60° of torsion according to Murphy had 40° of torsion according to Reikerås. All five methods for measuring femoral torsion showed excellent agreement for both intraobserver reproducibility (ICC, 0.905-0.973) and interobserver reliability (ICC, 0.938-0.969). Because the quantification of femoral torsion in hips with excessive femoral torsion differs considerably among measurement methods, it is crucial to state the applied methods when reporting femoral torsion and to be consistent regarding the used measurement method. These differences have to be considered for surgical decision-making and planning the degree of correction. Neglecting the differences among measurement methods to quantify femoral torsion can potentially lead to misdiagnosis and surgical planning errors. Level IV, diagnostic study.