The electron transport chain of Escherichia coli grown anaerobically with fumarate as terminal electron acceptor: an electron paramagnetic resonance study.
The electron transport chain of Escherichia coli grown anaerobically on glycerol with fumarate as terminal electron acceptor, has been studied using electron paramagnetic resonance (EPR) spectroscopy. The analysis did not include cytochromes, but was confined to the lower potential (dehydrogenase) section of the electron transport chain. Several ferredoxin-type centres were detected and partially characterized, and the possible presence of iron-sulphur centres paramagnetic in their oxidized form ('HiPIP-type') was also noted. An EPR-detectable signal that may have been due to the presence of molybdenum in the electron transport chain is described and assessed. Most of the centres detected were reducible by substrate in the absence of oxidant and some were found to be wholly or partly reduced during steady state oxidation of substrates in the presence of oxygen.


Expression Analysis of Cnidarian-Specific Neuropeptides in a Sea Anemone Unveils an Apical-Organ-Associated Nerve Net That Disintegrates at Metamorphosis.
Neuropeptides are ancient neuronal signaling molecules that have diversified across Cnidaria (e.g., jellyfish, corals, and sea anemones) and its sister group Bilateria (e.g., vertebrates, insects, and worms). Over the course of neuropeptide evolution emerged lineage-specific neuropeptides, but their roles in the evolution and diversification of nervous system function remain enigmatic. As a step toward filling in this knowledge gap, we investigated the expression pattern of a cnidarian-specific neuropeptide-RPamide-during the development of the starlet sea anemone Nematostella vectensis, using in situ hybridization and immunohistochemistry. We show that RPamide precursor transcripts first occur during gastrulation in scattered epithelial cells of the aboral ectoderm. These RPamide-positive epithelial cells exhibit a spindle-shaped, sensory-cell-like morphology, and extend basal neuronal processes that form a nerve net in the aboral ectoderm of the free-swimming planula larva. At the aboral end, RPamide-positive sensory cells become integrated into the developing apical organ that forms a bundle of long cilia referred to as the apical tuft. Later during planula development, RPamide expression becomes evident in sensory cells in the oral ectoderm of the body column and pharynx, and in the developing endodermal nervous system. At metamorphosis into a polyp, the RPamide-positive sensory nerve net in the aboral ectoderm degenerates by apoptosis, and RPamide expression begins in ectodermal sensory cells of growing oral tentacles. In addition, we find that the expression pattern of RPamide in planulae differs from that of conserved neuropeptides that are shared across Cnidaria and Bilateria, indicative of distinct functions. Our results not only provide the anatomical framework necessary to analyze the function of the cnidarian-specific neuropeptides in future studies, but also reveal previously unrecognized features of the sea anemone nervous system-the apical organ neurons of the planula larva, and metamorphosis-associated reorganization of the ectodermal nervous system.


Probably the most active population in the world: accelerometer measurements of 72 school-children in Greenland.
Physical activity is the most important lifestyle factor to contribute to a healthy early life. International recommendations are that children should be vigorously physically active for at least 1 h per day, and in Greenland, authorities have claimed a goal of being the world's most active population. Since 1994, the Health Behaviour in School-aged Children (HBSC) has measured physical activity among school-children in Greenland by questionnaire data, but the measurement properties of self-reported data in comparison to more objectively measured accelerometer data are unknown. The present paper describes the first study using clinical measures of physical activity among Greenlandic youth. Seventy-two school-children (56% girls) with a mean age of 12 years (range 25%; 75% was 11.5; 12.25) wore accelerometers for seven consecutive days, and data produced significant and informative findings for both practice and future research. Fifty-two per cent of the school-children met the international recommendations of being physically active >1 h per day, when measured by accelerometers, but self-reported data reported a prevalence of 10% meeting the recommendations. A majority of this sample of Greenlandic school-children lives up to international recommendations, which indicates that the goal of being the world's most active population is within reach.


Circulating Midregional Proadrenomedullin and Risk of Incident Abdominal Aortic Aneurysm: A Prospective Longitudinal Cohort Study.
Prospective clinical plasma biomarker studies in abdominal aortic aneurysm (AAA) pathogenesis have been hampered by the need for very large cohorts and long follow-up time. The main aim of the present study was to evaluate the association of adrenomedullin, a cardiovascular (CV) stress marker, and incident AAA risk. Prospective longitudinal cohort of middle-aged individuals from the CV cohort of the Malmö Diet and Cancer Study (n = 5551; 1991-1994) was assessed. Plasma concentrations of midregional proadrenomedullin (MR-proADM), C-reactive protein (CRP), and conventional risk factors were measured at baseline. Incidence of AAA was studied up to December 31, 2013. Cumulative incidence of AAA was 1.5% (men 2.9%, women 0.5%). Mean age of individuals with incident AAA was 59.7 years at study entry, and AAA was diagnosed on average 14 years later. Adjusting for age, gender, smoking, body mass index, hypertension, diabetes mellitus, and CRP, MR-proADM (hazard ratio: 1.28; 95% confidence interval: 1.01-1.62) was independently associated with incident AAA. The plasma biomarker MR-proADM seems to be a marker of AAA risk, implying that AAA development may be driven by long-standing CV stress on the aortic wall.


Synthesis and structural characterization of the peptide epitope of the ovarian cancer biomarker CA125 (MUC16).
A highly conserved region of 21 amino acids flanked by cysteine residues, contained within a larger repeated domain, has been proposed to be the antibody-binding site in the ovarian cancer biomarker CA125 (MUC16). In this study solid-phase peptide synthesis with Fmoc protection chemistry was used to assemble a 21-mer peptide corresponding to the most frequently occurring antibody binding sequence in CA125. Potentially significant sequence variants were also synthesized. Peptide secondary structure was investigated using Fourier transform infrared spectroscopy, revealing the consensus sequence peptide to be largely unstructured at physiological pH whether the cysteine residues were reduced or were oxidized to form an intramolecular disulfide bond. Substitution of serine for proline at position 8 (P8S) results in β-sheet formation in peptides involved in intramolecular disulfide bonds. This β-sheet structure does not persist in peptides incapable of intramolecular disulfide bonding because of sequence nor in peptides treated with the reducing agent dithiothreitol. In CA125, P8S is predicted to occur in ∼25% of repeat domains, suggesting that this structural motif is a non-negligible contributor to overall structure and function. These findings suggest that future structural characterization efforts of CA125 should be especially mindful of the amino acid sequence and oxidation state of the protein.


Impact of passive and active promotional strategies on patient acceptance of medication therapy management services.
To assess the impact of passive and active promotional strategies on patient acceptance of medication therapy management (MTM) services, and to identify reasons for patient acceptance or refusal. Four promotional approaches were developed to offer MTM services to eligible patients, including letters and bag stuffers ("passive" approaches), and face-to-face offers and telephone calls ("active" approaches). Thirty pharmacies in a grocery store chain were randomized to one of the four approaches. Patient acceptance rates were compared among the four groups, and between active and passive approaches using hierarchical logistic regression techniques. Depending on their decision to accept or decline the service, patients were invited to take part in one of two brief telephone surveys. No significant differences were identified among the four promotional methods or between active and passive methods in the analyses. Patients' most frequent reasons for accepting MTM services were potential cost savings, review of how the medications were working, the expert opinion of the pharmacist, and education about medications. Patients' most frequent reasons for declining MTM services were that the participant already felt comfortable with their medications and felt their pharmacist provides these services on a regular basis. No significant difference was found among any of the four groups or between active or passive approaches. Further research is warranted to identify strategies for improving patient engagement in MTM services.


Plasma pharmacokinetics and metabolism of 13-cis- and all-trans-retinoic acid in the cynomolgus monkey and the identification of 13-cis- and all-trans-retinoyl-beta-glucuronides. A comparison to one human case study with isotretinoin.
In order to compare the disposition and metabolism of 13-cis-retinoic acid (13-cis-RA) and all-trans-retinoic acid (all-trans-RA) in the nonpregnant female cynomolgus monkey, the plasma concentrations of the parent compound, the oxidized metabolites 4-oxo-13-cis-retinoic acid and 4-oxo-all-trans-retinoic acid, and the conjugate metabolites 13-cis-retinoyl-beta-glucuronide (13-cis-RAG) and all trans-retinoyl-beta-glucuronide (all-trans-RAG), were determined on day 1 and day 10 after oral dosing of 2 and 10 mg 13-cis- and all-trans-RA/kg/day. Both 13-cis-RAG and all-trans-RAG have been identified as major plasma metabolites in these studies using thermospray/HPLC/mass-spectrometry of the intact conjugates. AUC comparisons from 0-24 hr after administration indicated that 13-cis-RA treatment resulted in primarily cis metabolites and all-trans-RA treatment resulted in primarily trans metabolites, although low levels of isomerization products were observed. Comparison of the two doses (2 and 10 mg/kg, po) revealed that the AUCs were proportional to the dose administered. Although qualitatively similar, elimination of 13-cis-RA in the monkey was more rapid than in the human, and approximately a 10-fold greater dose of 13-cis-RA was required in the monkey to produce the AUC values comparable to the human. The elimination of all-trans-RA in monkey was faster than that of 13-cis-RA and tended to increase with repeated dosing.(ABSTRACT TRUNCATED AT 250 WORDS)


Synthesis of quinazoline-3-oxides via a Pd(ii) catalyzed azide-isocyanide coupling/cyclocondensation reaction.
A novel and efficient protocol concerning palladium catalyzing the three-component reaction of 2-azidobenzaldehyde, isocyanide, and hydroxylamine hydrochloride is developed. This method allows the rapid elaboration of quinazoline 3-oxides in a one-pot fashion. The 3-CR mainly involves concatenation of azide-isocyanide denitrogenative coupling, condensation with hydroxylamine and 6-exo-dig cyclization. The salient features of the methodology are operational simplicity, use of milder reaction conditions, being devoid of any additives such as oxidants (redox neutral) or base, and releasing N2 and H2O as the byproducts.


Risk of recurrence after a first unprovoked venous thromboembolism: external validation of the Vienna Prediction Model with pooled individual patient data.
In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to their recurrence risk and to identify those who would actually benefit from indefinite anticoagulation, three prediction models have been developed so far; none of them has been yet externally validated. To externally validate the Vienna Prediction Model (VPM), a prediction guide for estimating the recurrence risk after a first unprovoked VTE developed through Cox modeling and including sex, D-dimer and index VTE site as predictors. Nine hundred and four patients pooled from five prospective studies evaluating the prognostic value of D-dimer for VTE recurrence served as the validation cohort. The validity of the VPM in stratifying patients according to their relative recurrence risk (discrimination) and in predicting the absolute recurrence risk (calibration) was tested with survival analysis methods. The ability of the VPM to distinguish patients' risk for recurrent VTE in the validation cohort was at least as good as in the original cohort, with a calibration slope of 1.17 (95% confidence interval 0.71-1.64; P = 0.456 for the hypothesis of a significant difference from 1), and a c-statistic of 0.626 (vs. 0.651 in the original derivation cohort). The VPM absolute predictions in terms of cumulative rates tended to underestimate the observed recurrence rates at 12 months. By using a pooled individual patient database as a validation cohort, we confirmed the ability of the VPM to stratify patients with a first unprovoked VTE according to their risk of recurrence.


Robust Recurrent CNV Detection in the Presence of Inter-Subject Variability.
The study of recurrent copy number variations (CNVs) plays an important role in understanding the onset and evolution of complex diseases such as cancer. Array-based comparative genomic hybridization (aCGH) is a widely used microarray based technology for identifying CNVs. However, due to high noise levels and inter-sample variability, detecting recurrent CNVs from aCGH data remains a challenging topic. This paper proposes a novel method for identification of the recurrent CNVs. In the proposed method, the noisy aCGH data is modeled as the superposition of three matrices: a full-rank matrix of weighted piece-wise generating signals accounting for the clean aCGH data, a Gaussian noise matrix to model the inherent experimentation errors and other sources of error, and a sparse matrix to capture the sparse inter-sample (sample-specific) variations. We demonstrated the ability of our method to separate accurately recurrent CNVs from sample-specific variations and noise in both simulated (artificial) data and real data. The proposed method produced more accurate results than current state-of-the-art methods used in recurrent CNV detection and exhibited robustness to noise and sample-specific variations.


PTBP1 Positively Regulates the Translation of Circadian Clock Gene, Period1.
Circadian oscillations of mRNAs and proteins are the main features of circadian clock genes. Among them, Period1 (Per1) is a key component in negative-feedback regulation, which shows a robust diurnal oscillation and the importance of circadian rhythm and translational regulation of circadian clock genes has been recognized. In the present study, we investigated the 5'-untranslated region (5'-UTR) of the mouse core clock gene, Per1, at the posttranscriptional level, particularly its translational regulation. The 5'-UTR of Per1 was found to promote its translation via an internal ribosomal entry site (IRES). We found that polypyrimidine tract-binding protein 1 (PTBP1) binds to the 5'-UTR of Per1 and positively regulates the IRES-mediated translation of Per1 without affecting the levels of Per1 mRNA. The reduction of PTBP1 level also decreased the endogenous levels of the PER1 protein but not of its mRNA. As for the oscillation of PER1 expression, the disruption of PTBP1 levels lowered the PER1 expression but not the phase of the oscillation. PTBP1 also changed the amplitudes of the mRNAs of other circadian clock genes, such as Cryptochrome 1 (Cry1) and Per3. Our results suggest that the PTBP1 is important for rhythmic translation of Per1 and it fine-tunes the overall circadian system.


[May Thurner syndrome with ischemic cerebrovascular accident and permeable oval foramen].
The association of cerebral ischemic attack with patent foramen ovale has not been extensively studied, and frequently the site of origin of embolism is not detected despite routine studies. We present the case of a young patient with ischemic stroke and permeable oval foramen in the context of May Thurner syndrome. The May Thurner syndrome is an entity scarcely studied in the medical literature and it has also been infrequently related to ischemic vascular cerebral accident, but in patients with permeable oval foramen without evidence of the emboligen source, it is interesting to rule it out as a cause of paradoxical embolism.


Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review.
To report an update on the role of vitamin D (VD) in ovarian physiology with a focus on genes involved in steroidogenesis, follicular development, and ovarian reserve, as well as ovulatory dysfunction associated with polycystic ovary syndrome (PCOS), and ovarian response to assisted reproductive technology (ART). Systematic review. Not applicable. Human, animal, and cell culture models. Pubmed literature search. Granulosa cell function, serum antimüllerian hormone (AMH), AMH and its receptor gene expression, soluble receptor for advanced glycation end-products (sRAGE), PCOS parameters, and ART outcome. In human granulosa cells, VD alters AMH signaling, FSH sensitivity, and progesterone production and release, indicating a possible physiologic role for VD in ovarian follicular development and luteinization. In the serum, 25-hydroxyvitamin D (25OH-D) is positively correlated with AMH, and appropriate VD supplementation in VD-depleted women can suppress the seasonal changes that occur in serum AMH. In VD-deficient women with PCOS, VD supplementation lowers the abnormally elevated serum AMH levels, possibly indicating a mechanism by which VD improves folliculogenesis. The antiinflammatory sRAGE serum levels significantly increase in women with PCOS after VD replacement. Although follicular fluid 25OH-D correlates with IVF outcomes, there is a lack of data pertaining to the impact of VD supplementation on pregnancy rates following IVF. This review underscores the need for understanding the mechanistic actions of VD in ovarian physiology and the critical need for randomized trials to elucidate the impact of VD supplementation on controlled ovarian hyperstimulation/IVF outcome and ovulatory dysfunction associated with PCOS.


Insights from In Vivo Studies of Cellular Senescence.
Cellular senescence is the dynamic process of durable cell-cycle arrest. Senescent cells remain metabolically active and often acquire a distinctive bioactive secretory phenotype. Much of our molecular understanding in senescent cell biology comes from studies using mammalian cell lines exposed to stress or extended culture periods. While less well understood mechanistically, senescence in vivo is becoming appreciated for its numerous biological implications, both in the context of beneficial processes, such as development, tumor suppression, and wound healing, and in detrimental conditions, where senescent cell accumulation has been shown to contribute to aging and age-related diseases. Importantly, clearance of senescent cells, through either genetic or pharmacological means, has been shown to not only extend the healthspan of prematurely and naturally aged mice but also attenuate pathology in mouse models of chronic disease. These observations have prompted an investigation of how and why senescent cells accumulate with aging and have renewed exploration into the characteristics of cellular senescence in vivo. Here, we highlight our molecular understanding of the dynamics that lead to a cellular arrest and how various effectors may explain the consequences of senescence in tissues. Lastly, we discuss how exploitation of strategies to eliminate senescent cells or their effects may have clinical utility.


Biological treatment of ammonia gas at high loading.
The exhaust gas from compost processing plants contains a large amount of ammonia. To treat ammonia gas at high loads, bench-scale experiments were carried out. First, nitrifying bacteria were enriched from soil and immobilized on porous ceramics. The ceramics were packed in an acrylic cylinder (diameter, 100 mm; packed height, 190 mm) and ammonia gas was introduced to the top of the cylinder. The concentration and flow rate of ammonia gas were gradually increased and finally 85 ppm was introduced at a space velocity of 800 h(-1) (empty bed residence time (EBRT), 4.5 sec). The ammonia load was 1.0 kg N/m3 day(-1). The exhaust contained 1.5-2 ppm of ammonia. Then the packed ceramics were transferred to another acrylic cylinder (diameter, 50 mm; packed height, 800 mm). A high concentration of ammonia gas (1,000 ppm) was introduced at a space velocity of 96 h(-1) (ammonia loading, 1.44 kg N/m3 day(-1); EBRT, 37.5 sec). The exhaust contained 2 ppm of ammonia (removal rate, 99.8%). The packed bed was washed with water intermittently or continuously, and the wastewater from the cylinder contained a large amount of ammonium and nitrate ions of at a 1:1 ratio. Stoichiometric analysis showed that half of the introduced ammonia was oxidized to nitrate, and the rest was converted to ammonium ion. Thus, ammonia gas was effectively treated at a high load by biofiltration with nitrifying bacteria.


Differences in Perceived Risk of Contracting SARS-CoV-2 during and after the Lockdown in Sub-Saharan African Countries.
This study investigated risk perception of contracting and dying of SARS-CoV-2 in sub-Sahara Africa during and after the lockdown periods. Two online surveys were conducted one year apart, with participants 18 years and above living in sub-Sahara Africa or the diaspora. Each survey took four weeks. The first survey was taken from 18 April to 16 May 2020, i.e., during the lockdown. The second survey was taken from 14 April to 14 May 2021, i.e., after the lockdown. A cross-sectional study using adopted and modified questionnaires for both surveys were distributed through online platforms. Question about risks perception of contracting and dying of SARS-CoV-2 were asked. The Helsinki declaration was applied, and ethical approvals were obtained. Total responses for both surveys, i.e., both during and after the lockdown, was 4605. The mean age was similar in both surveys (18-28 years). The mean risk perception scores were higher after lockdown by 3.59%. Factors associated with risk perception of COVID-19 were survey period, age group, region of residence, and occupation. Non-health care workers had a lower risk perception of COVID-19. This first comparative study on the level of risk perception of Africans during and after the lockdown shows that one in every three and every four persons in sub-Sahara Africa felt at high risk of contracting COVID-19 and thought they could die from contracting the same, respectively.


Looking sharp: Becoming a search template boosts precision and stability in visual working memory.
Visual working memory (VWM) plays a central role in visual cognition, and current work suggests that there is a special state in VWM for items that are the goal of visual searches. However, whether the quality of memory for target templates differs from memory for other items in VWM is currently unknown. In this study, we measured the precision and stability of memory for search templates and accessory items to determine whether search templates receive representational priority in VWM. Memory for search templates exhibited increased precision and probability of recall, whereas accessory items were remembered less often. Additionally, while memory for Templates showed benefits when instances of the Template appeared in search, this benefit was not consistently observed for Accessory items when they appeared in search. Our results show that becoming a search template can substantially affect the quality of a representation in VWM.


The Relationship of Dry Eye Disease With Depression in Saudi Arabia: A Cross-Sectional Study.
Objective Estimate the prevalence of depression among individuals with a dry eye disease (DED) in Saudi Arabia using two questionnaires: Patient Health Questionnaire (PHQ-9) and Dry Eye Questionnaire (DEQ-5), and explore potential factors implicated in the development of depression among the DED population. Methods This is a descriptive cross-sectional study of 476 patients with DED which was conducted using a PHQ-9 questionnaire to screen for depression and a DEQ-5 questionnaire to diagnose DED. The questionnaires were merged and distributed using Google Forms through various social media platforms targeting the Saudi population. After data collection, it was revised, coded and fed to statistical software IBM SPSS version 22 (SPSS, Inc. Chicago, IL). Results Depression was diagnosed among 200 participants (42%) of the cases with dry eyes. From which 5.7% had mild depression, 13.9% had moderate depression, 12.6% had moderately severe depression, and 9.9% had severe depression. A female predominance was noticed; 44.7% of the females with dry eyes had depression compared to 32.4% of males with recorded statistical significance (P=0.023). Depression was detected among 55% of those who are less than 20 years old in comparison to 27% of those who are 30 years or older (P=0.001). Laser-assisted in-situ keratomileusis (LASIK), prolonged electronic device usage and contact lens wear are reported as risk factors associated with an increase in dry eye symptoms. However, there is no statistically significant relationship between contact lens wear and depression among dry eye disease patients. Conclusion Suffering from DED is a possible risk factor for developing depression as DED is associated with depression of higher degrees of severity. Depression among DED patients is found to be significantly more prevalent among females and the young adult population rather than older adults.


The prevalence and determinants of body dysmorphic disorder among young social media users: A cross-sectional study.
Social media that is heavily used in Saudi Arabia has been linked to a negative impact on body image satisfaction. The objective of the current study was to examine the burden, determinants, and impacts of Body Dysmorphic Disorder (BDD) among a community sample of social media users in Saudi Arabia. The Internet-based cross-sectional study was conducted among social media users during January and February 2020. BDD was assessed using a validated BDD Questionnaire. A total of 1010 participants were included in the current analysis. A total of 42 (4.2%) met the criteria of BDD, with higher prevalence in younger participants. The defects of high concerns were skin disfigurements (64.2%) and hair issues (42.3%). BDD was significantly associated with spending a longer time on Snapchat and Instagram and less interest in religious topics. BDD group was more likely to compare their appearance with famous people in social media. BDD group reported more harassment and more history of psychiatric problems. There is a need to educate the public about the risk of BDD and to promote safe social networking.


Effects of a bovine herpesvirus-1 isolate on reproductive function in heifers: classification as a type-2 (infectious pustular vulvovaginitis) virus by restriction endonuclease analysis of viral DNA.
A bovine herpesvirus-1 (BHV-1) isolate (FI) from an aborted fetus was used to infect 9 heifers at various stages of gestation. Two heifers were inoculated IV on postbreeding day (PBD) 1, 7, or 14, and 3 heifers were inoculated in the sixth month of pregnancy. Plasma progesterone assays were used to monitor corpus luteum function in heifers inoculated during early pregnancy. Low progesterone values and infertility were seen in the 2 heifers inoculated on PBD 1. Luteal function remained normal in heifers inoculated on PBD 7 or 14. These 4 heifers inoculated on PBD 7 or 14 carried their fetuses to term, and their calves were free of BHV-1 infection at birth. Three heifers inoculated during the sixth month of pregnancy also carried their fetuses to term. Two calves were born alive, and BHV-1 was not isolated from nasal swab samples of either calf; the third calf was stillborn. Virus was not isolated from the stillborn calf's tissues, but BHV-1 was isolated from the placenta. Lesions were not detected in several tissues examined by light microscopy, and BHV-1 antigen was not detected by immunohistochemical examination of paraffin sections. Restriction endonuclease analysis of viral DNA was used to compare the FI virus to other BHV-1 isolates (Colorado-1, Iowa, and K22). On the basis of restriction endonuclease analysis, the FI isolate should be classified as a type-2 (infectious pustular vulvovaginitis) virus, specifically subtype a.


Evidence gaps and research needs in current guidance on feeding children from birth to 24 months.
A United States National Academies report summarized recommendations on what and how to feed infants and young children in high-income countries from 43 eligible guideline documents. Consistency existed across many recommendations, but some differences occurred in topic areas, age groupings, and methodological approaches. Future development of guidelines on feeding of infants and young children requires new research and a rigorous evidence-based review process that is harmonized within and across countries and incorporates dissemination and implementation guidance. Novelty: New research and rigorous methods are recommended to develop future harmonized guidance on feeding of infants and young children that incorporates dissemination and implementation methods.


Allelic variation in cell wall candidate genes affecting solid wood properties in natural populations and land races of Pinus radiata.
Forest trees are ideally suited to association mapping due to their high levels of diversity and low genomic linkage disequilibrium. Using an association mapping approach, single-nucleotide polymorphism (SNP) markers influencing quantitative variation in wood quality were identified in a natural population of Pinus radiata. Of 149 sites examined, 10 demonstrated significant associations (P < 0.05, q < 0.1) with one or more traits after accounting for population structure and experimentwise error. Without accounting for marker interactions, phenotypic variation attributed to individual SNPs ranged from 2 to 6.5%. Undesirable negative correlations between wood quality and growth were not observed, indicating potential to break negative correlations by selecting for individual SNPs in breeding programs. Markers that yielded significant associations were reexamined in an Australian land race. SNPs from three genes (PAL1, PCBER, and SUSY) yielded significant associations. Importantly, associations with two of these genes validated associations with density previously observed in the discovery population. In both cases, decreased wood density was associated with the minor allele, suggesting that these SNPs may be under weak negative purifying selection for density in the natural populations. These results demonstrate the utility of LD mapping to detect associations, even when the power to detect SNPs with small effect is anticipated to be low.


The Maze operation for treatment of atrial fibrillation. Early clinical experience in a Scandinavian institution.
The Maze operation is a potentially curative surgical option in patients with disabling atrial fibrillation (AF) refractory to conventional treatment. The aim of this study was to evaluate the initial 4-year Maze experience in our institution. The study included 26 patients (19 males, mean age 55 years) who had undergone the Maze (III) operation between 1994 and 1998. Nine patients had surgery for concomitant heart disease. Follow-up was 3-55 (median 18) months. No deaths or neurological complications occurred; 22 patients are at present in regular sinus-, or junctional rhythm, 2 patients have permanent atrial pacing for symptomatic sinus node dysfunction, and 2 patients have had persistent AF, post surgery. Sinus node dysfunctions were detected in five patients, though not requiring pacemakers. Out of the total 26 patients, 23 are free of anti-arrhythmic drugs. Echocardiographic signs of left atrial contraction were recorded in 50% of the patients. The Maze operation offers a safe alternative to conventional therapy, with attractive results justifying expansion in the use of this treatment for AF.


Brief communication: Sex determination accuracy of the minimum supero-inferior femoral neck diameter in a contemporary rural Guatemalan population.
One hundred and fourteen femora (75 male and 39 female) derived from a contemporary rural Guatemalan population were studied to test the ability of the minimum supero-inferior femoral neck diameter as a sex indicator. With the discriminant functions previously developed from North American modern populations, a maximum of only 36% correctly sexed femora was obtained, with correct percentages as low as 4%. A new discriminant function for the Guatemalan rural population is presented, with a total of 89.5% correctly classified individuals. It is suggested that poor physical growth of the rural Guatemalan population, due to a stressful environment, can explain part of the metric differences observed between the North American and rural Guatemalan populations.


[Compartmentalized portal hypertension after spleno-renal shunt occlusion (author's transl)].
This is a report of a patient with a thrombosed distal spleno-renal shunt with gastro-splenic disconnection and post-operative recurrent variceal hemorrhage. After portocaval shunt, a high venous pressure in the gastro-splenic sector demonstrates a compartmentalized venous hypertension. Splenectomy normalized this segmental portal hypertension, this confirming the concept that this type of portosystemic shunt is selective in early post-operative period.


Acute eosinophilic appendicitis after generalized skin reaction due to unknown cause in a child: Case report and literature review.
Acute eosinophilic appendicitis (AEA) is a rare variant of appendix inflammation possibly linked to allergy. Histopathological evidence of eosinophilic infiltration of the muscularis propria and edema separating the muscle fibers is the gold standard for the diagnosis. Here, we report a case of a young boy with AEA following a skin reaction of possible allergic origin. A 6-year-old male was presented to the emergency department with a two-day diffuse abdominal pain and tenderness in the right lower quadrant. A possible allergic reaction had occurred five days before as a pruritic rash. There was no history of allergy and the stool examination was negative for parasites. The initial diagnosis was acute appendicitis, and appendectomy was performed. The histopathological diagnosis was AEA. Further studies on the proper diagnostic and treatment approach of AEA before surgery are required.


Visual Outcomes in the Management of Diabetic Maculopathy in Central Australia.
In major urban centres and high-resource settings, treatment of diabetic maculopathy with anti-Vascular Endothelial Growth Factor (VEGF) injections has largely displaced laser treatment. However, intravitreal therapy alone requires frequent follow-up, a barrier to adherence in remote Australia. We report vision outcomes of phased diabetic maculopathy treatment in remote Central Australia for maculopathy using laser and, in a subset, supplementary injection treatment. We audited clinical records of patients undergoing laser treatment for diabetic maculopathy between 2001 and 2013 at an ophthalmology service based at Alice Springs Hospital, a regional hub in remote Australia. All patients receiving macular laser treatment were included, and some required supplementary injection(s). The primary outcome measure was change in best-corrected visual acuity [BCVA] from baseline treatment. Of 338 maculopathy-treated patients, 88% were indigenous and 39% were male. Of 554 maculopathy laser-treated eyes, 118 (21%) received supplementary injection/s. In the laser treatment phase, median BCVA was 78 letters at baseline (interquartile range 62-80) and decreased by a median of two letters at final visit. In the subset who underwent subsequentinjection treatment, BCVA was 60 letters at first injection, with a median five-letter increase by final visit. Overall outcomes were similar in Indigenous and non-Indigenous Australians. Predictors of reduction in BCVA in the macular laser treatment phase were better baseline BCVA, older age, and PRP treatment (all p < .005). Laser treatment for diabetic maculopathy preserved vision in Central Australia, where barriers to follow-up can preclude regular injections. Supplementary injections stabilized vision in the laser-resistant subset.


Advances in cyanobacterial polyhydroxyalkanoates production.
Polyhydroxyalkanoates (PHAs) have received much attention in the current scenario due to their attractive material properties, namely biodegradability, biocompatibility, thermoplasticity, hydrophobicity, piezoelectricity and stereospecificity. All these properties make them highly competitive for various industrial applications similar to non-degradable conventional plastics. In PHA biosynthesis, PHA synthase acts as a natural catalyst for PHA polymerization process using the (R)-hydroxyacyl-CoA as substrate. Cyanobacteria can accumulate PHAs under photoautotrophic and/or mixotrophic growth conditions with organic substrates such as acetate, glucose, propionate, valerate, and so on. The natural incidence of PHA accumulation by the cyanobacteria is known since 1966. Nevertheless, PHA accumulation in cyanobacteria based on the cell biomass and volumetric productivity is critically lower than the heterotrophic bacteria. Consequently, cyanobacteria are nowadays not considered for commercial production of PHAs. Thus, strain improvements by genetic modification, new cultivation and harvesting techniques, advanced photobioreactor development, efficient and sustainable downstream processes, alternate economical carbon sources and usage of various metabolic inhibitors are suggested for enhancing cyanobacterial PHA accumulation. In addition, identification of transcriptional regulators like RNA polymerase sigma factor (SigE) and a response regulator (Rre37) together with the recent major scientific breakthrough on the existence of complete Krebs cycle in cyanobacteria would be helpful in taking PHA production from cyanobacteria to a new-fangled height in near future.


Mother-child interaction revisited: communication with non-speaking physically disabled children.
This paper presents an in-depth analysis of the interaction between mothers and their severely physically disabled children who have motor speech disorders. The study was designed to partially replicate previous investigations, most notably those undertaken by Light et al., to examine if the patterns of conversation previously described were observed in interaction involving children of a wide age range. Twenty children who had four-limb cerebral palsy, with no diagnosed learning difficulties or sensory impairments, and who were between 2 and 10 years of age inclusive participated in the research with their mothers. Children's speech was unintelligible to their parents out of context and most had been provided with aided communication systems. Other carers were excluded from the research due to possible differences in interaction style. Conversation between mothers and children was videotaped in a standard play situation. The toys used to stimulate interaction had been shown to elicit the full range of communication skills targeted in the present study from non-disabled children. Videotaped interaction was coded to show the structure of conversation and the functions used. The mode of communication used by the children was also recorded. In addition, communicative functions were elicited from the children in a semi-scripted conversation with a clinician developed from that used by Light et al. Structural moves and communicative functions used by mothers and children were examined using mean proportions. Sequential analysis of mother-child interaction was also undertaken at both levels to investigate the patterns that recurred in conversation. Results support those obtained in previous studies, showing restricted conversation patterns and high levels of maternal directiveness. Mothers initiated most communicative exchanges, asking many questions and issuing many requests for attention, objects or activities. Children across the age range produced more response moves than any other move type. Their responses contained yes/no answers and acknowledgements, and to a lesser extent provisions of information. When children did produce communicative functions other than simple confirmation, denials and acknowledgements, they were often not fully understood and were followed by requests for clarification by the mothers. Children produced a wider range of communicative functions in the semi-scripted elicitation conversation with the clinician than in conversation with their mothers (z = 3.52, p = 0.0002). The results obtained support those of previous research and suggest that interaction for children with severe motor and speech impairments becomes 'fossilized', changing little throughout childhood. Findings support the two-pronged approach to intervention for children using augmentative communication systems that is now developing. Intervention should focus not only on the children, teaching them how to use their augmentative systems and to produce a full range of conversation skills, but also should focus on their carers. Training for carers aims to increase their interaction skills, teaching them how to facilitate and expand children's communication skills.


Health risk of swimming pool disinfection by-products: a regulatory perspective.
While disinfection of swimming pools is indispensable for microbiological safety, it may lead to the formation of disinfection by-products. Most studies agree that inhalation exposure is the predominant pathway of the associated health risks, but assumptions are based on concentrations measured in water and evaporation models. Pool water and air were sampled in 19 swimming pools. Trihalomethanes were detected in all sites; chloroform being the most abundant species. Concentrations ranged between 12.8-71.2 μg/L and 11.1-102.2 μg/m3 in pool water and air, respectively. The individual lifetime carcinogenic risk associated with chloroform in swimming pools exceeded 10-6 in all age groups for recreational swimmers and 10-5 for elite swimmers and staff, even if the pool complied with the national standards. Inhalation exposure was estimated and found to be the most relevant, however, different mass transfer models from water measurements significantly under- or overestimated the health burden compared to direct calculation from the concentration in air. The observed health risks call for defining regulatory values and monitoring requirement of indoor air quality in swimming pools.


Clinical phase I/II trial to investigate neoadjuvant intensity-modulated short term radiation therapy (5 × 5 Gy) and intraoperative radiation therapy (15 Gy) in patients with primarily resectable pancreatic cancer - NEOPANC.
The current standard treatment, at least in Europe, for patients with primarily resectable tumors, consists of surgery followed by adjuvant chemotherapy. But even in this prognostic favourable group, long term survival is disappointing because of high local and distant failure rates. Postoperative chemoradiation has shown improved local control and overalls survival compared to surgery alone but the value of additional radiation has been questioned in case of adjuvant chemotherapy. However, there remains a strong rationale for the addition of radiation therapy considering the high rates of microscopically incomplete resections after surgery. As postoperative administration of radiation therapy has some general disadvantages, neoadjuvant and intraoperative approaches theoretically offer benefits in terms of dose escalation, reduction of toxicity and patients comfort especially if hypofractionated regimens with highly conformal techniques like intensity-modulated radiation therapy are considered. The NEOPANC trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant short course intensity-modulated radiation therapy (5 × 5 Gy) in combination with surgery and intraoperative radiation therapy (15 Gy), followed by adjuvant chemotherapy according to the german treatment guidelines, in patients with primarily resectable pancreatic cancer. The aim of accrual is 46 patients. The primary objectives of the NEOPANC trial are to evaluate the general feasibility of this approach and the local recurrence rate after one year. Secondary endpoints are progression-free survival, overall survival, acute and late toxicity, postoperative morbidity and mortality and quality of life. NCT01372735.


The differential similarity of positive and negative information - an affect-induced processing outcome?
People judge positive information to be more alike than negative information. This good-bad asymmetry in similarity was argued to constitute a true property of the information ecology (Alves, H., Koch, A., & Unkelbach, C. (2017). Why good is more alike than bad: Processing implications. Trends in Cognitive Sciences, 21, 69-79). Alternatively, the asymmetry may constitute a processing outcome itself, namely an influence of phasic affect on information processing. Because no research has yet tested whether phasic affect influences perceived similarity among stimuli, we conducted 5 Experiments that also tested whether phasic affect can account for the higher judged similarity among positive compared to negative stimuli. In three experiments, we affectively charged pictures of different Pokemon by pairing them with monetary gains and losses (Exp. 1a, 1b) as well as positive and negative trait words (Exp. 2); yet, the evaluative charge did not differentially influence perceived similarity among the Pokemon. Experiment 3 replicated the basic similarity asymmetry among positive and negative words, and found that it was unaffected by externally induced phasic affect. Experiment 4 showed that phasic affect had no influence on perceived similarity of non-evaluative words either. We conclude that albeit a weak influence of phasic affect on perceived similarity of stimuli cannot be ruled out entirely, it can most likely not account for the typically medium to large sized asymmetry in similarity among positive and negative stimuli.


Polarization maintaining silica waveguide resonator optic gyro using double phase modulation technique.
Resonator micro optic gyro (RMOG) is a promising candidate for applications requiring small, light and robust gyros. In optical passive ring resonator gyros, clockwise and counter clockwise lightwaves are modulated at different frequencies to reduce the backscattering induced noise. The effectiveness of this technique, however, is determined by the carrier suppression level. Accurate modulation index and high environmental temperature stability is required for achieving high total carrier suppression for the traditional single phase modulation technique (SPMT). In this paper, we propose an RMOG based on the double phase modulation technique (DPMT). Compared with the traditional SPMT, two additional phase modulations are added to provide additional carrier suppression. It is found that the control accuracy of the modulation index and temperature stability is relaxed more than 30 times. It is easily performed for reducing the backscattering error below the shot noise limited sensitivity. The modulation parameters in the DPMT are analyzed and optimized. Based on the optimum parameters of the DPMT, a bias stability of 1.85×10⁻⁴ rad/s is successfully demonstrated in the polarization maintaining silica waveguide resonator with the length of 7.9 cm. This is the best result reported to date, to the best of our knowledge, for a waveguide type passive ring resonator gyro.


Polyethylenimine as a promising vector for targeted siRNA delivery.
Recent discovery of RNA interference (RNAi) technology for gene therapy has triggered explosive research efforts towards development of small interfering RNA (siRNA) as therapeutic modality for gene silencing. Owing to its large molecular weight (~13 kDa), polyanionic nature (~40 negative phosphate groups) and rapid enzymatic degradation, delivery of siRNA remains an unresolved issue. Hence, there arises a need of an appropriate delivery vector to overcome the intrinsic, poor intracellular uptake and limited in vitro and in vivo stability. Amongst the various non-viral delivery vectors, the application of polymeric vectors such as polyethylenimine (PEI) or its derivatives has attracted much attention due to its high transfection efficiency and ease of manipulation. PEI has been extensively investigated for DNA delivery, only recently this polymer has been employed for siRNA delivery. This review will focus on studies done on PEI to deliver siRNA, with emphasis on the targeted, self-assembled polymeric nanoparticles with promising potential to evolve as therapeutic tool in gene therapy.


Comparison of the Effects of Five Semen Extenders on the Quality of Frozen-Thawed Equine Epididymal Sperm.
Cryopreservation of epididymal sperm allows the saving of genetic material in case of unexpected death or emergency castration. The aim of the present study was the comparison of five different combinations of extenders commercially available for equine frozen semen processing for cryopreservation of epididymal sperm. Epididymal sperm were harvested from gonads of 10 healthy stallions after routine castration by retrograde flush technique. Then, samples were split and diluted with (1) INRA96 + INRA Freeze, (2) BotuSemen + BotuCRIO, (3) EquiPlus + Gent Freeze, (4) EquiPlus + EquiPlus Freeze, and (5) Gent + Gent Freeze. Extenders 1 and 2 showed higher values for total and progressive motility after thawing compared with extender 4 (P < .05). Extender 3 was in between 1 and 2 (P > .05), and extender 5 resulted in the lowest values (P < .05). The subpopulation of viable frozen-thawed sperm with high mitochondrial membrane potential and low intracellular calcium content was higher using extender 1 compared with extenders 3, 4, and 5 (P < .05) and higher in extender 2 compared with extenders 4 and 5 immediately after thawing (P < .05). After 1 hour of incubation, this subpopulation yielded the highest values in extender 2 (P < .05). Immediately after thawing, extender 1 yielded higher values for percentage of DFI and mean DFI than extenders 3, 4, and 5 (P < .05). Following 1 hour of incubation after thawing, sperm processed with extender 1 resulted in the highest values for percentage of DFI and mean DFI (P < .05). Using extender 2, mean DFI values were lower than those in extender 1 and higher than the extenders 3, 4, and 5 (P < .05). The study revealed that according to the examined sperm quality parameters, freezing extenders (extender 1, extender 2) using low concentrations of glycerol either combined with or without methylformamide were beneficial for cryopreservation of stallion epididymal sperm. For processing of stallion epididymal sperm, an extender containing milk proteins (extenders 1-4) for initial dilution after sperm harvesting is preferable to an extender including egg yolk (extender 5).


Failed escape: solid surfaces prevent tumbling of Escherichia coli.
Understanding how bacteria move close to surfaces is crucial for a broad range of microbial processes including biofilm formation, bacterial dispersion, and pathogenic infections. We used digital holographic microscopy to capture a large number (>10(3)) of three-dimensional Escherichia coli trajectories near and far from a surface. We found that within 20 μm from a surface tumbles are suppressed by 50% and reorientations are largely confined to surface-parallel directions, preventing escape of bacteria from the near-surface region. A hydrodynamic model indicates that the tumble suppression is likely due to a surface-induced reduction in the hydrodynamic force responsible for the flagellar unbundling that causes tumbling. These findings imply that tumbling does not provide an effective means to escape trapping near surfaces.


Functional analysis of a histone deacetylase-like protein of Thermus caldophilus GK24 in mammalian cell.
The function of eukaryotic histone deacetylase (HDAC) has been extensively studied for its critical role in transcriptional regulation and carcinogenesis. However that of the prokaryotic counterpart remains largely unknown. Recently, we cloned HDAC-like protein in Thermus caldophilus GK24 (Tca HDAC) from a genomic library of the microorganism based on homology analysis with human HDAC1. To explore the function of Tca HDAC in mammalian cells, Tca HDAC gene expressing vector was transfected into a human fibrosarcoma cell line, HT1080. Tca HDAC was mainly localized in nuclei of the mammalian cells as a human HDAC1 was, due to an N-terminal HDAC association domain. We further generated histidine-substituted Tca HDAC mutants and investigated their role in biochemical and cellular activity of the enzyme. Tca HDAC mutants exhibited dramatic loss of enzymatic activity and conditioned media (CM) from HT1080 cells transfected with mutant Tca HDAC was unable to stimulate angiogenic phenotypes of endothelial cells in vitro whereas that of wild Tca HDAC did. Collectively, these results demonstrate that a prokaryotic histone deacetylase from T. caldophilus GK24 is functionally active in mammalian cells and its function in gene expression is conserved from prokaryotes to eukaryotes.


Chemistry and biology of tubulysins: antimitotic tetrapeptides with activity against drug resistant cancers.
Since their first report in 2000, tubulysins have sparked great interest for development as anti-cancer agents due to their exceptionally potent antiproliferative activity. Progress in the discovery and development of tubulysins, especially tubulysin conjugates, has quickly advanced despite limitations in their availability from Nature. In this Highlight, the key research on the isolation and structure determination, biosynthesis, bioactivity, structure-activity relationships (SAR), synthesis, and conjugates of tubulysins is presented.


Hierarchical self-assembly of patchy colloidal platelets.
Anisotropy at the level of the inter-particle interaction provides the particles with specific instructions for the self-assembly of target structures. The ability to synthesize non-spherical colloids, together with the possibility of controlling the particle bonding pattern via suitably placed interaction sites, is nowadays enlarging the playing field for materials design. We consider a model of anisotropic colloidal platelets with regular rhombic shape and two attractive sites placed along adjacent edges and we run Monte Carlo simulations in two-dimensions to investigate the two-stage assembly of these units into clusters with well-defined symmetries and, subsequently, into extended lattices. Our focus is on how the site positioning and site-site attraction strength can be tuned to obtain micellar aggregates that are robust enough to successively undergo to a second-stage assembly from sparse clusters into a stable hexagonal lattice.


Mechanisms of evolutionary change in structural plumage coloration among bluebirds (Sialia spp.).
Combinations of microstructural and pigmentary components of barbs create the colour displays of feathers. It follows that evolutionary changes in colour displays must reflect changes in the underlying production mechanisms, but rarely have the mechanisms of feather colour evolution been studied. Among bluebirds in the genus Sialia, male rump colour varies among species from dark blue to light blue while breast colour varies from blue to rusty. We use spectrometry, transmission electron microscopy and Fourier analysis to identify the morphology responsible for these divergent colour displays. The morphology of blue rump barbs is similar among the three species, with an outer keratin cortex layer surrounding a medullary 'spongy layer' and a basal row of melanin granules. A spongy layer is also present in blue breast barbs of mountain bluebirds Sialia currucoides and in rusty breast barbs of western Sialia mexicana and eastern bluebirds Sialia sialis. In blue barbs melanin is basal to the spongy layer, but is not present in the outer cortex or spongy layer, while in rusty barbs, melanin is present only in the cortex. The placement of melanin in the cortex masks expression of structural blue, creating a rusty display. Such shifts in microstructures and pigments may be widespread mechanisms for the evolutionary changes in the colours of feathers and other reflective structures across colourful organisms.


Intramedullary versus extramedullary alignment of the tibial component in the Triathlon knee.
Long term survivorship in total knee arthroplasty is significantly dependant on prosthesis alignment. Our aim was determine which alignment guide was more accurate in positioning of the tibial component in total knee arthroplasty. We also aimed to assess whether there was any difference in short term patient outcome. A comparison of intramedullary versus extramedullary alignment jig was performed. Radiological alignment of tibial components and patient outcomes of 103 Triathlon total knee arthroplasties were analysed. Use of the intramedullary was found to be significantly more accurate in determining coronal alignment (p = 0.02) while use of the extramedullary jig was found to give more accurate results in sagittal alignment (p = 0.04). There was no significant difference in WOMAC or SF-36 at six months. Use of an intramedullary jig is preferable for positioning of the tibial component using this knee system.


[Albumin dialysis in complex intensive therapy].
After cardiac surgery, acute hepatic failure (AHF) is a most common component of the multiple organ dysfunction syndrome (MODS) and associated with high mortality. In the past year, A. N. Bakulev Research Center of Cardiovascular Surgery, Russian Academy of Medical Sciences, has performed 10 postoperative MARS therapy sessions in patients with MODS caused by the development of low cardiac output. The results of the study suggest that MARS therapy has no negative impact on circulatory parameters under adequate thermoregulation monitoring. During albumin dialysis, there is a reduction in bilirubin levels by the end of a session, a significant decrease in the parameters of uremic intoxication: urea and creatinine. The studies of the values of albumin in different constituents of an extracorporeal contour have indicated the preservation of a significant gradient of the protein concentrations between the patient's blood and a dialyzing solution, which is indicative of the absence of laboratory significant permeability of a MARS filter for these molecules. Thus, the first experience in using MARD therapy suggests that it may be successfully used in patients with MODS after cardiacsurgery.


Organisational impact of the National Disability Insurance Scheme transition on mental health care providers: the experience in the Australian Capital Territory.
Concerns raised about the appropriateness of the National Disability Insurance Scheme (NDIS) in Australia for people with mental illness have not been given full weight due to a perceived lack of available evidence. In the Australian Capital Territory (ACT), one of the pilot sites of the Scheme, mental health care providers across all relevant sectors who were interviewed for a local Atlas of Mental Health Care described the impact of the scheme on their service provision. All mental health care providers from every sector in the ACT were contacted. The participation rate was 92%. We used the Description and Evaluation of Services and Directories for Long Term Care to assess all service provision at the local level. Around one-third of services interviewed lacked funding stability for longer than 12 months. Nine of the 12 services who commented on the impact of the NDIS expressed deep concern over problems in planning and other issues. The transition to NDIS has had a major impact on ACT service providers. The ACT was a best-case scenario as it was one of the NDIS pilot sites.


A Distinct, Sequence-Induced Conformation Is Required for Recognition of the Constitutive Decay Element RNA by Roquin.
The constitutive decay element (CDE) of tumor necrosis factor α (TNF-α) mRNA (Tnf) represents the prototype of a class of RNA motifs that mediate rapid degradation of mRNAs encoding regulators of the immune response and development. CDE-type RNAs are hairpin structures featuring a tri-nucleotide loop. The protein Roquin recognizes CDE-type stem loops and recruits the Ccr4-Caf1-Not deadenylase complex to the mRNA, thereby inducing its decay. Stem recognition does not involve nucleotide bases; however, there is a strong stem sequence requirement for functional CDEs. Here, we present the solution structures of the natural Tnf CDE and of a CDE mutant with impaired Roquin binding. We find that the two CDEs adopt unique and distinct structures in both the loop and the stem, which explains the ability of Roquin to recognize stem loops in a sequence-specific manner. Our findings result in a relaxed consensus motif for prediction of new CDE stem loops.


Does living longer in good health facilitate longer working lives? The relationship between disability and working lives.
Improvements in life expectancy have fuelled debates about the statutory retirement age in many European countries. This article contributes to this debate by investigating how changes in disability may influence both employment outcomes and disability-free life expectancy. We used data from the European Community Household Panel to estimate the impact of disability incidence on labour supply by country using propensity score techniques. In a second step, we translated the estimated effects of disability incidence into effects on working life expectancy as well as disability-free life expectancy using multi-state life tables. Results from the matching analysis show that individuals who become disabled are more likely to leave the labour market. However, the size of the effect is much weaker than a simple descriptive analysis suggests and varies by country. A 10% decrease in disability incidence results in increases in disability-free life expectancy and working life expectancy of respectively 0.6 and 0.07 years on average. A large part of the differences in employment between disabled and non-disabled individuals is not due to a causal effect of disability on employment. Policies that reduce disability incidence increase disability-free life expectancy but have only a limited impact on working life expectancy.


Genetic variation in the gene LRP2 increases relapse risk in multiple sclerosis.
Due to the lack of prospective studies with longitudinal data on relapse, past genetic studies have not attempted to identify genetic factors that predict relapse risk (the primary endpoint of many pivotal clinical trials testing the efficacy of multiple sclerosis (MS) disease-modifying drugs) at a genome-wide scale. We conducted a genome-wide association analysis (GWAS) to identify genetic variants that predict MS relapse risk, using a three-stage approach. First, GWAS was conducted using the southern Tasmania MS Longitudinal Study with 141 cases followed prospectively for a mean of 2.3 years. Second, GWAS was conducted using the Ausimmune Longitudinal Study with 127 cases having a classic first demyelinating event followed for 5 years from onset. Third, the top hits with p<5.0×10-6 from the first two stages were combined with a longitudinal US paediatric MS cohort with 181 cases followed for 5 years after onset. Predictors of time to relapse were evaluated by a mixed effects Cox model. An inverse variance fixed effects model was then used to undertake a meta-analysis. In the pooled results, using these three unique longitudinal MS cohorts, we discovered one novel locus (LRP2; most significant single nucleotide polymorphism rs12988804) that reached genome-wide significance in predicting relapse risk (HR=2.18, p=3.30×10-8). LRP2 is expressed on the surface of many central nervous system cells including neurons and oligodendrocytes and is a critical receptor in axonal guidance. The finding of a genetic locus that has extensive effects on neuronal development and repair is of interest as a potential modulator of MS disease course.


Physicochemical characterization of nanoparticles and their behavior in the biological environment.
Whilst the physical and chemical properties of nanoparticles in the gas or idealized solvent phase can nowadays be characterized with sufficient accuracy, this is no longer the case for particles in the presence of a complex biological environment. Interactions between nanoparticles and biomolecules are highly complex on a molecular scale. The detailed characterization of nanoparticles under these conditions and the mechanistic knowledge of their molecular interactions with the biological world is, however, needed for any solid conclusions with regards to the relationship between the biological behavior of such particles and their physicochemical properties. In the present article we discuss some of the challenges with characterization and behavior of nanoparticles that are associated with their presence in chemically complex biological environments. Our focus is on the stability of colloids as well as on the formation and characteristics of protein coronae that have recently been shown to significantly modify the properties of pristine particles. Finally, we discuss the perspectives that may be expected from an improved understanding of nanoparticles in biological media.


Bingeing, self-restriction, and increased body weight in rats with limited access to a sweet-fat diet.
Prior research has shown that fasting alternated with a diet of standard rodent chow and a 10% sucrose solution produces bingeing on the sucrose, but animals remain at normal body weight. The present study investigated whether restricted access to a highly palatable combination of sugar and fat, without food deprivation, would instigate binge eating and also increase body weight. Male rats were maintained for 25 days on one of four diets: (i) sweet-fat chow for 2 h/day followed by ad libitum standard chow, (ii) 2-h sweet-fat chow only 3 days/week and access to standard chow the rest of the time, (iii) ad libitum sweet-fat chow, or (iv) ad libitum standard chow. Both groups with 2-h access to the sweet-fat chow exhibited bingeing behavior, as defined by excessively large meals. The body weight of these animals increased due to large meals and then decreased between binges as a result of self-restricted intake of standard chow following binges. However, despite these fluctuations in body weight, the group with 2-h access to sweet-fat chow every day gained significantly more weight than the control group with standard chow available ad libitum. These findings may have implications for the body weight fluctuations associated with binge-eating disorder, as well as the relationship between binge eating and the obesity epidemic.


Summing nondetects: incorporating low-level contaminants in risk assessment.
Low-level contaminants often are present below the detection or reporting limits of a laboratory, resulting in values reported as a nondetect or less-than. How can these values be summed along with detected concentrations to obtain a total, particularly when weighting factors such as toxic equivalence factors (TEFs) are used? The most common method employed by environmental scientists for summing nondetects along with detected values is to substitute one-half the detection limit for each nondetect. This substitution allows the least precise measurements, data with high detection limits, to have a strong influence on the resulting total amount. Substitution methods have repeatedly been shown to provide substandard results in studies over the last 2 decades. Here an alternative, the Kaplan-Meier (KM) method used throughout the fields of medical and industrial statistics, is used to obtain the total. KM estimates are far less affected by the least precise data than are estimates computed using substitution. No assumptions about the distribution of data (whether they follow a normal or other distribution) need be made. Direct application of KM to computation of toxicity equivalence concentrations (TECs) is shown.


Development of an mHealth trauma registry in the Middle East using an implementation science framework.
Trauma registries (TRs) play a vital role in the assessment of trauma care, but are often underutilized in countries with a high burden of injuries. We investigated whether information and communications technology (ICT) such as mobile health (mHealth) could enable the design of a tablet-based application for healthcare professionals. This would be used to inform trauma care and acquire surveillance data for injury control and prevention in Oman. This paper focuses on documenting the implementation process in a healthcare setting. The study was conducted using an ICT implementation framework consisting of multistep assessment, development and pilot testing of an electronic tablet-based TR. The pilot study was conducted at two large hospitals in Oman, followed by detailed evaluation of the process, system and impact of implementation. The registry was designed to provide comprehensive information on each trauma case from the location of injury until hospital discharge, with variables organized to cover 11 domains of demographic and clinical information. The pilot study demonstrated that the registry was user friendly and reliable, and the implementation framework was useful in planning for the Omani hospital setting. Data collection by trained and dedicated nurses proved to be more feasible, efficient and reliable than real-time data entry by care providers. The initial results show the promising potential of a user-friendly, comprehensive electronic TR through the use of mHealth tools. The pilot test in two hospitals indicates that the registry can be used to create a multicenter trauma database.


Study protocol: a cluster randomised controlled trial of a school based fruit and vegetable intervention - Project Tomato.
The School Fruit and Vegetable Scheme (SFVS) is an important public health intervention. The aim of this scheme is to provide a free piece of fruit and/or vegetable every day for children in Reception to Year 2. When children are no longer eligible for the scheme (from Year 3) their overall fruit and vegetable consumption decreases back to baseline levels. This proposed study aims to design a flexible multi-component intervention for schools to support the maintenance of fruit and vegetable consumption for Year 3 children who are no longer eligible for the scheme. This study is a cluster randomised controlled trial of Year 2 classes from 54 primary schools across England. The schools will be randomly allocated into two groups to receive either an active intervention called Project Tomato, to support maintenance of fruit intake in Year 3 children, or a less active intervention (control group), consisting of a 5 A DAY booklet. Children's diets will be analysed using the Child And Diet Evaluation Tool (CADET), and height and weight measurements collected, at baseline (Year 2) and 18 month follow-up (Year 4). The primary outcome will be the ability of the intervention (Project Tomato) to maintain consumption of fruit and vegetable portions compared to the control group. A positive result will identify how fruit and vegetable consumption can be maintained in young children, and will be useful for policies supporting the SFVS. A negative result would be used to inform the research agenda and contribute to redefining future strategies for increasing children's fruit and vegetable consumption. Medical Research Council Registry code G0501297.


The impact of tobacco prices on smoking onset in Vietnam: duration analyses of retrospective data.
The benefits of preventing smoking onset are well known, and even just delaying smoking onset conveys benefits. Tobacco control policies are of critical importance to low-income countries with high smoking rates such as Vietnam where smoking prevalence is greater than 55 % in young men between the ages of 25 and 45. Using a survey of teens and young adults, I conducted duration analyses to explore the impact of tobacco price on smoking onset. The results suggest that tobacco prices in Vietnam have a statistically significant and fairly substantial effect on the onset of smoking. Increases in average tobacco prices, measured by an index of tobacco prices and by the prices of two popular brands, are found to delay smoking onset. Of particular interest is the finding that Vietnamese youth are more sensitive to changes in prices of a popular international brand that has had favourable tax treatment since the late 1990s.


Diagnosis of small intestinal bacterial overgrowth: the challenges persist!
Small intestinal bacterial overgrowth was originally defined in the context of an overt malabsorption syndrome and diagnostic tests were developed and validated accordingly. More recently, the concept of intestinal contamination with excessive numbers of bacteria, especially those of colonic type, has been extended beyond the bounds of frank maldigestion and malabsorption to explain symptomatology in disorders as diverse as irritable bowel syndrome, celiac sprue and nonalcoholic fatty liver disease. Owing to a lack of consensus with regard to the optimal diagnostic criteria (the 'gold standard') for the diagnosis of bacterial overgrowth, the status of these new concepts is unclear. This review sets out to critically appraise the various diagnostic approaches that have been taken and are currently employed to diagnose small intestinal bacterial overgrowth.


Resection of hepatocellular carcinoma after transcatheter arterial embolization. Reevaluation of the advantages and disadvantages of preoperative embolization.
Hepatocellular carcinomas (HCCs) were resected in eight patients who had preoperative transcatheter arterial embolization (TAE) and in 25 patients without preoperative TAE. Three patients in the former group had ruptured HCCs before operation. Two of the former group and three of the latter group were found to have recurrences after a follow-up of 1 1/2 years. Although preoperative TAE resulted in significantly increased tumor necrosis, it increased the risk of gangrenous change of the gallbladder, induced adhesion of the hepatoduodenal ligament, and was not effective in reducing operative blood loss or operative time if the vessel selected for TAE was inadequate. Pathologic examination revealed tumor emboli still existing in the intrahepatic veins. Daughter nodules and capsular invasion by tumor cells were not affected by TAE. Transcatheter arterial embolization seems to be effective in controlling bleeding from ruptured HCC prior to staged resection of the tumor.


[On the front line: survey on shared responsibility. General practitioners and schizophrenia].
General practitioners (GP) play a preponderant role in the treatment of patients suffering of schizophrenia. Discovering the number of patients with schizophrenia who are treated by GPs ; the needs and attitudes of GPs, their knowledge concerning diagnosis, and the treatment they provide. A postal survey was conducted with Quebec GPs who were randomly chosen. A total of 1003 GPs have participated in the survey. Among them, a small percentage have to treat an early onset schizophrenia and the GPs have expressed their wish to be more informed on the accessibility of specialized services. Results pertaining to questions on diagnoses and knowledge on treatments are inconsistent. The majority of GPs treat the first psychotic episodes with antipsychotic medication. Only a third of GPs surveyed propose maintaining the treatment after a first psychotic episode, in accordance with international recommendations and the recent Canadian guidelines on practices that recommends at least 6 to 12 months of treatment after a partial or complete clinical response. Time given by male GPs to a first contact varies between 10 and 20 minutes, while 80 % of female GPs spend at least 20 minutes. The adverse effects of antipsychotic medication that raise most concern is weight gain before neurological signs. some of this survey's data should be considered by various professional and governmental associations, in order to improve the place of GPs in a health plan destined to treat schizophrenia.


TDP-43 pathology in the population: prevalence and associations with dementia and age.
The significance of TDP-43 pathology in relation to aging and dementia in the population is unclear. We aimed to determine the prevalence of transactive response DNA-binding protein of 43 kDA (TDP-43) neuronal inclusions in a population-based sample, and associations with age group at death (≤90 and >90 years) and clinical dementia status prior to death. Further, we investigate associations between TDP-43 inclusions and other key dementia-related neuropathologies (plaques, tangles, and neuronal loss) within the hippocampus and entorhinal and temporal cortices. All brain donors within the Cambridge City over-75 s Cohort (CC75C), which is population-based and longitudinally tracked (n = 228), were included. Age at death ranged from 78 to 106 years. TDP-43 neuronal inclusions were assessed in the hippocampus, entorhinal cortex, and temporal cortex. These data were combined with existing clinical and neuropathological data. TDP-43 neuronal inclusions were present in 27% of the sample, 36% of those with clinical dementia and 18% without dementia. Individuals who died later (>90 years) or with clinical dementia were more likely to show TDP-43 inclusions. Hippocampal and entorhinal TDP-43 inclusions were significantly associated with dementia severity and increasing age, taking into account other neuropathologies. TDP-43 neuronal inclusions appeared to be co-localize with severe neuronal loss. Findings indicate that hippocampal and entorhinal TDP-43 inclusions are important substrates of late onset dementia which appear to co-localize with severe neuronal loss, but not with Alzheimer's disease markers of amyloid and tau. This broadens the accepted view of TDP-43 pathology in dementias.


The ethics of managed care: challenges to the principles of relationship-centered care.
Health care reform involves ethical issues on many levels. First, the impetus to reform the health care system stems in large part from concerns about equity, just distribution of goods and services, and commitments to one another in society. Health care itself is more than a commodity, it is a personal healing activity carried out through institutions that embody values such as respect for persons, the value of human life, and duties to care for individuals who suffer. These issues fall under major overarching concerns on the macro level. Reform, however, often functions as a euphemism for changing the health care system to provide greater profitability, and for controlling costs. Admittedly, such changes can be disguised under reforming the health care system, and indeed, some of them are capable of enhancing and simultaneously making more efficient, our care for one another when sick. Most changes, nonetheless, are clearly driven from less noble ideals. Every schema for providing care also embodies values since these schemas presuppose various competing notions of justice and equity. Further, they may endanger long-held values of health care providers in meeting the needs of patients. As part of state or local-level changes in the health care system, issues in this category can be called micro level concerns. when all the changes impact on individuals, either providers of care, or the patients themselves, then the issues are of concern on the personal level. This essay, therefore, examines ethical issues presented by managed care networks on the macro, micro, and individual level, with special attention paid to the health care relationship. The subtitle of the essay points out the focus of the discussion on the impact of these changes for more traditional models of relationship-centered care.1 In particular, the essay concentrates on health providers, including allied health professionals, that in the past were grouped into the category of primary care givers but ought to be called first-level care givers today.


Porosity and thermal collapse measurements of H2O, CH3OH, CO2, and H2O:CO2 ices.
The majority of astronomical and laboratory based studies of interstellar ices have been focusing on ice constituents. Ice structure is a much less studied topic. Particularly the amount of porosity is an ongoing point of discussion. A porous ice offers more surface area than a compact ice, for reactions that are fully surface driven. In this paper we discuss the amount of compaction for four different ices--H2O, CH3OH, CO2 and mixed H2O : CO2 = 2 : 1--upon heating over an astronomically relevant temperature regime. Laser interference and Fourier transform infrared spectroscopy are used to confirm that for amorphous solid water the full signal loss of dangling OH bonds is not a proof for full compaction. These data are compared with the first compaction results for pure CH3OH, pure CO2 and mixed H2O : CO2 = 2 : 1 ice. Here we find that thermal segregation benefits from a higher degree of porosity.


Methods in regression analysis in surgical oncology research-best practice guidelines.
Using real working examples, we provide strategies and address challenges in linear and logistic regression to demonstrate best practice guidelines and pitfalls of regression modeling in surgical oncology research. To demonstrate our best practices, we reviewed patients who underwent tissue expander breast reconstruction between 2019 and 2021. We assessed predictive factors that affect BREAST-Q Physical Well-Being of the Chest (PWB-C) scores at 2 weeks with linear regression modeling and overall complications and malrotation with logistic regression modeling. Model fit and performance were assessed. The 1986 patients were included in the analysis. In linear regression, age [β = 0.18 (95% CI: 0.09, 0.28); p < 0.001], single marital status [β = 2.6 (0.31, 5.0); p = 0.026], and prepectoral pocket dissection [β = 4.6 (2.7, 6.5); p < 0.001] were significantly associated with PWB-C at 2 weeks. For logistic regression, BMI [OR = 1.06 (95% CI: 1.04, 1.08); p < 0.001], age [OR = 1.02 (1.01, 1.03); p = 0.002], bilateral reconstruction [OR = 1.39 (1.09, 1.79); p = 0.009], and prepectoral dissection [OR = 1.53 (1.21, 1.94); p < 0.001] were associated with increased likelihood of a complication. We provide focused directives for successful application of regression techniques in surgical oncology research. We encourage researchers to select variables with clinical judgment, confirm appropriate model fitting, and consider clinical plausibility for interpretation when utilizing regression models in their research.


[Respiration activity of frozen-thawed lymphoid cells].
The respiration and oxidative phosphorylation rate of lymphocytes were studied after their cryopreservation. The oxygen uptake of cells frozen in the freezing medium containing 20% serum and 10% PEO-400 or DMSO is higher than that of the native lymphocytes. 2,4-DNP has not demonstrated any stimulating effect on the frozen-thawed cell respiration. Succinate has significantly stimulated the respiration of cells frozen with PEO-400 and produces a slight stimulating effect on the respiration of cells frozen with DMSO. It is concluded that the mitochondria and plasma membranes of cryopreserved lymphocytes undergo considerable changes.


Understanding the causes of recent warming of mediterranean waters. How much could be attributed to climate change?
During the past two decades, Mediterranean waters have been warming at a rather high rate resulting in scientific and social concern. This warming trend is observed in satellite data, field data and model simulations, and affects both surface and deep waters throughout the Mediterranean basin. However, the warming rate is regionally different and seems to change with time, which has led to the question of what causes underlie the observed trends. Here, we analyze available satellite information on sea surface temperature (SST) from the last 25 years using spectral techniques and find that more than half of the warming tendency during this period is due to a non-linear, wave-like tendency. Using a state of the art hydrodynamic model, we perform a hindcast simulation and obtain the simulated SST evolution of the Mediterranean basin for the last 52 years. These SST results show a clear sinusoidal tendency that follows the Atlantic Multidecadal Oscillation (AMO) during the simulation period. Our results reveal that 58% of recent warming in Mediterranean waters could be attributed to this AMO-like oscillation, being anthropogenic-induced climate change only responsible for 42% of total trend. The observed acceleration of water warming during the 1990s therefore appears to be caused by a superimposition of anthropogenic-induced warming with the positive phase of the AMO, while the recent slowdown of this tendency is likely due to a shift in the AMO phase. It has been proposed that this change in the AMO phase will mask the effect of global warming in the forthcoming decades, and our results indicate that the same could also be applicable to the Mediterranean Sea. Henceforth, natural multidecadal temperature oscillations should be taken into account to avoid underestimation of the anthropogenic-induced warming of the Mediterranean basin in the future.


Comparative study on the hepatoprotection to heavy metals of Zingiber officinale.
Zingiber officinale (Zingiberaceae) is a herb used for culinary and therapeutic purposes due to its anti-inflammatory and antioxidant potentials. We examined its protective ability against mercury (Hg), lead (Pb) and cadmium (Cd) accumulation in the liver. MATERIALS #ENTITYSTARTX00026; Ground Zingiber officinale (7%, w/w of feed) was administered to rats either at the same time with the exposure ofheavy metals (group 2), a week after exposure to heavy metals (group 3) or given a week before heavy metal exposure (group 4) for six weeks. Animals were exposed to either of Hg (10 ppm), Cd (200 ppm) and Pb (100 ppm) in drinking water. The heavy metal accumulations in the liver were determined using AAS. Weight losses induced by these metals were not reversed by Zingiber officinale administration. There was a significant (P<0.01) increase in protection to Pb (97%) and Cd (63%) accumulation when compared to Hg (32%) at week 2. The protective ability was significantly (P<0.01) decreased at week 4 when compared to week 2 for Cd and Pb but not to Hg in groups 3 (50%) and 4 (52%). At week 6, hepatoprotection to Hg (44%) and Cd (85%) was significantly (P<0.01) different but not to Pb which was only significant (P<0.05) in week 2 of treatment for all groups. Zingiber officinale affected the bioavailability, elimination and uptake of these metals in a time-dependent way with highest beneficial reducing effect to Cd followed by Hg and least protection to Pb in the liver.


Clinical, Biochemical and Molecular Characteristics of the Main Types of Porphyria.
Porphyrias are diverse disorders that arise from various inherited enzyme defects in the heme biosynthesis pathway, except for porphyria cutanea tarda (PCT), in which the enzyme deficiency in most cases is acquired. The biosynthetic blocks resulting from the defective enzymes are largely expressed either in the liver or bone marrow, the sites where the majority of heme is produced. Although the pathophysiologic mechanisms of the clinical manifestations of the porphyrias are not fully understood, two cardinal features prevail: skin photosensitivity and neurologic symptoms of intermittent autonomic neuropathy, acute neurovisceral attacks, and disorders of the nervous system. The primary diagnosis of the proband is based on biochemical testing, which is not always able to identify acute porphyrias, especially in asymptomatic family carriers when heme precursors and porphyrins excretion is normal, low-normal and high-reduced values of enzyme activity overlap, and hematological diseases responsible for abnormal blood cells distribution coexist. Molecular analysis of gene mutations responsible for each type of porphyria is the best diagnostic approach for symptomatic as well as presymptomatic gene carriers.


[The students' page. Are we making good use of this space?].
The current study aimed to make a survey of the articles written by nursing students that were published through the Students' Pages in the Brazilian Nursing Journal, Nursing Journal from Bahia and Nursing Journal from São Paulo from 1982 to 1995, in order to verify if this space is being used and the themes that have been approached. This investigation evidenced that, from the three studied periodicals, 109 issues were available in the library, 15 presented articles published in the Students' Pages and 21 texts were found. Among these, the most approached themes are related to nursing practice.


Identification of a unique apolipoprotein E allele in Microcebus murinus; ApoE brain distribution and co-localization with beta-amyloid and tau proteins.
This report is devoted to the characterization of the apolipoprotein E (ApoE) in Microcebus murinus. Only one allele homologous to the human ApoE4 allele was evidenced. The distribution of the corresponding ApoE protein in the brain was found in association with the pathological proteins characteristic of Alzheimer's disease (AD). Immunocytochemistry revealed brain deposits of ApoE in: (1) the cortical amyloid plaques; (2) the neurones of the various cortical lobes, the hippocampus and the brainstem; (3) the glial cells, astrocytes of the cortical parenchym and oligodendrocytes of the corpus callosum; and (4) the vessel walls. Most ApoE, beta-amyloid protein, abnormally phosphorylated Tau proteins and gliofilament acid proteins were seen in the same cortical areas. These findings for ApoE report the view that Microcebus murinus, in captivity, presents a pathological profile very similar to that observed in AD.


Biological interaction of cigarette smoking on the association between genetic polymorphisms involved in inflammation and the risk of lung cancer: A case-control study in Japan.
Chronic inflammation serves an important role in lung carcinogenesis, thus genetic polymorphisms involved in this pathway may affect the risk of lung cancer. The present case-control study focused on the association between lung cancer risk and genetic polymorphisms involved in inflammatory pathways. The study comprised 462 lung cancer cases and 379 controls from Japan. The roles of interleukin 8 (IL8) rs4073, nuclear factor kappa B (NFκB) rs28362491, cytochrome b-245, alpha polypeptide (CYBA) rs4673, NAD(P) H dehydrogenase, quinone 1 (NQO1) rs1800566, nitric oxide synthase 2 and inducible (NOS2) rs2297518 polymorphisms in lung carcinogenesis were investigated. An unconditional logistic model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between the genetic polymorphisms and lung cancer risk. The multiplicative and additive [relative excess risk due to interaction, attributable proportion due to interaction (AP) and synergy index (SI)] interactions with cigarette smoking were also determined. A significant association was revealed between the TT genotype of NQO1 rs1800566 and an increased risk of lung cancer (OR=1.78; 95% CI=1.14-2.79). The additive interaction evaluations between CYBA rs4673 (AP=0.50, 95% CI=0.15-0.85; SI=2.66, 95% CI=1.01-6.99) and smoking were also statistically significant. NQO1 rs1800566 was significantly associated with lung cancer risk and smoking may influence the association between CYBA rs4673 and the risk of lung cancer. Additional studies with larger control and case populations are warranted in order to confirm the CYBA rs4673-smoking association suggested by the present study.


Mobile Self-Monitoring ECG Devices to Diagnose Arrhythmia that Coincide with Palpitations: A Scoping Review.
The use and deployment of mobile devices across society is phenomenal with an increasing number of individuals using mobile devices to track their everyday health. However, there is a paucity of academic material examining this recent trend. Specifically, little is known about the use and deployment of mobile heart monitoring devices for measuring palpitations and arrhythmia. In this scoping literature review, we identify the contemporary evidence that reports the use of mobile heart monitoring to assess palpitations and arrhythmia across populations. The review was conducted between February and March 2018. Five electronic databases were searched: Association for Computing Machinery (ACM), CINHAL, Google Scholar, PubMed, and Scopus. A total of 981 records were identified and, following the inclusion and exclusion criteria, nine papers formed the final stage of the review. The results identified a total of six primary themes: purpose, environment, population, wearable devices, assessment, and study design. A further 24 secondary themes were identified across the primary themes. These included detection, cost effectiveness, recruitment, type of setting, type of assessment, and commercial or purpose-built mobile device. This scoping review highlights that further work is required to understand the impact of mobile heart monitoring devices on how arrhythmias and palpitations are assessed and measured across all populations and ages of society. A positive trend revealed by this review demonstrates how mobile heart monitoring devices can support primary care providers to deliver high levels of care at a low cost to the service provider. This has several benefits: alleviation of patient anxiety, lowering the risk of morbidity and mortality, while progressively influencing national and international care pathway guidelines. Limitations of this work include the paucity of knowledge and insight from primary care providers and lack of qualitative material. We argue that future studies consider qualitative and mixed methods approaches to complement quantitative methodologies and to ensure all actors' experiences are recorded.


Differential vulnerability of white matter structures to experimental infantile hydrocephalus detected by diffusion tensor imaging.
The differential vulnerability of white matter (WM) to acute and chronic infantile hydrocephalus and the related effects of early and late reservoir treatment are unknown, but diffusion tensor imaging (DTI) could provide this information. Thus, we characterized WM integrity using DTI in a clinically relevant model. Obstructive hydrocephalus was induced in 2-week-old felines by intracisternal kaolin injection. Ventricular reservoirs were placed 1 (early) or 2 (late) weeks post-kaolin and tapped frequently based solely on neurological deficit. Hydrocephalic and age-matched control animals were sacrificed 12 weeks postreservoir. WM integrity was evaluated in the optic system, corpus callosum, and internal capsule prereservoir and every 3 weeks using DTI. Analyses were grouped as acute (<6 weeks) or chronic (≥6 weeks). In the corpus callosum during acute stages, fractional anisotropy (FA) decreased significantly with early and late reservoir placement (p = 0.0008 and 0.0008, respectively), and diffusivity increased significantly in early (axial, radial, and mean diffusivity, p = 0.0026, 0.0012, and 0.0002, respectively) and late (radial and mean diffusivity, p = 0.01 and 0.0038, respectively) groups. Chronically, the corpus callosum was thinned and not detectable by DTI. FA was significantly lower in the optic chiasm and tracts (p = 0.0496 and 0.0052, respectively) with late but not early reservoir placement. In the internal capsule, FA in both reservoir groups increased significantly with age (p < 0.05) but diffusivity remained unchanged. All hydrocephalic animals treated with intermittent ventricular reservoir tapping demonstrated progressive ventriculomegaly. Both reservoir groups demonstrated WM integrity loss, with the CC the most vulnerable and the optic system the most resilient.


Serial antinuclear antibodies titre in pleural and pericardial fluid.
The antinuclear antibodies (ANA) test has been a cornerstone of the evaluation of connective tissue disease. The aim of this study was to investigate the diagnostic value of the ANA test in pleural or pericardial effusions of unknown causes. Over a 3-yr period, a total of 126 pleural fluid and 30 pericardial fluid samples were analysed. ANA tests were performed using a commercially available kit. The ANA kit used an indirect immunofluorescent antibody method with a human epithelial (HEP-2) cell line as substrate. Patients with high fluid ANA titre (>1:160) received a second aspiration 2 weeks after the initial aspiration if diagnosis was not confirmed. ANA results were positive in 39 pleural and 10 pericardial fluid samples. All but one of the effusions with positive ANA testing were exudative. Eleven pleural or pericardial effusions due to active systematic lupus erythematosus were identified and all had high ANA titres (1:160) with various staining patterns. Thirty-eight of 145 patients (26%) with effusions of nonlupus aetiologies had positive ANA testing in pleural or pericardial fluid. Thirteen of these 38 patients had high ANA titre. Malignant or paramalignant effusions constituted 11 of the 13 samples. In conclusion, although a negative antinuclear antibodies test makes a diagnosis of lupus serositis unlikely, high antinuclear antibodies titres in pleural or pericardial fluid are not diagnostic of lupus serositis even when as high as 1:5,120. An unexplained high antinuclear antibodies titre in pleural or pericardial effusion warrants search for malignancy.


Early sonographic detection of fetal intestinal obstruction and possible diagnostic pitfalls.
We present five fetuses at 15-17 weeks' gestation with a sonographic diagnosis of intestinal obstruction. Dilation of the intestine was the presenting sonographic finding in fetuses with a volvulus and/or anal atresia. Two of the fetuses also had other abnormalities. Intestinal peristalsis may be observed in early pregnancy as transient dilation of intestinal segments. Sonographers are cautioned about a false-positive diagnosis of intestinal obstruction in such cases.