Histological analysis of trematodes in Dreissena polymorpha: their location, pathogenicity, and distinguishing morphological characteristics.
Four families of trematodes were observed in histological sections during a 1992-1997 investigation of the parasites of zebra mussels Dreissena polymorpha. These included Aspidogastridae, i.e., Aspidogaster, Echinostomatidae, Bucephalidae, i.e., Bucephalus polymorphus, and Gorgoderidae, i.e., Phyllodistomumfolium. This article describes the precise location of these trematodes in the tissues of D. polymorpha, provides graphic evidence of their effect on the organs they inhabit, and highlights the distinguishing morphological characteristics. Evidence of defense reaction of host to trematode infection, i.e., encapsulation of Aspidogaster and nacrezation of B. polymorphus, is also presented and is the first such report for zebra mussels. The histological photomicrographs included represent the first comprehensive series published on trematode infection of zebra mussels. These images, in conjunction with the morphological descriptions presented, should assist researchers in identifying the 4 major trematode taxa that they are likely to encounter in the tissue sections of zebra mussels.


The common mechanisms of anterior cruciate ligament injuries in judo: a retrospective analysis.
Although high prevalence of anterior cruciate ligament injuries (ACL) in judokas has been reported, there has been very little research concerning events preceding the injury. To determine the common situations and mechanisms of ACL injury in judo. A total of 43 cases of ACL injuries that had occurred during judo competition or practice were investigated, using questionnaires with interviews conducted by a single certified athletic trainer who has 20 years of judo experience to obtain information regarding the situation and mechanism in which the ACL injury occurred. The number of ACL injuries when the participant's grip style was different from the style of the opponent (ie, kenka-yotsu style) (28 cases) was significantly greater than when the participant's grip style was the same as that of the opponent (ie, ai-yotsu style) (15 cases; p<0.001). The number of ACL injuries was significantly higher when the participant was attacked by the opponent than when counterattacked or when attempting the attack (p<0.001). In addition, being attacked with osoto-gari was revealed as the leading cause of ACL injury incidence among the participants (16.8%). Grip style may be associated with ACL injury occurrence in judo. In addition, direct contact due to the opponent's attack may be a common mechanism for ACL injuries in judo.


Controlling the ion release from mixed alkali bioactive glasses by varying modifier ionic radii and molar volume.
Partially substituting one alkali oxide for another reduces the crystallisation tendency and improves the processing of bioactive glasses. Here, we investigate how we can use alkali ions of varying ionic radii to control glass degradation and ion release from Bioglass 45S5. Partially replacing sodium by lithium reduced ion release in static and dynamic dissolution studies in Tris buffer, while ion release increased with increasing potassium for sodium substitution. While the mixed alkali effect is known to reduce ion release from conventional silicate glasses (compared to compositions containing one alkali oxide only), in the glasses studied here ion release was controlled by the packing of the silicate network, described by glass molar volume and oxygen density. Incorporating an alkali ion of smaller ionic radius (Li for Na or Na for K) resulted in a more compact network of higher oxygen density, which reduced ion release. On the other hand, an alkali ion of larger ionic radius (K for Na or Na for Li) expanded the silicate network, allowing for faster ion release. This can be explained by water molecules penetrating an expanded silicate network more easily than a more compact one, thereby directly influencing the ion exchange between modifier ions and protons from the dissolution medium. This shows that the use of modifier ions of varying ionic radii allows for tailoring bioactive glass ion release and degradation while maintaining silicate network polymerisation and network connectivity. And, indeed, recent literature suggests that this concept can be extended to other modifiers besides alkali metal ions, making it possible to design bioactive glasses of tailored solubility.


Infant feeding and HIV in Sub-Saharan Africa: what lies beneath the dilemma?
The debate over how to best guide HIV-infected mothers in resource-poor settings on infant feeding is more than two decades old. Globally, breastfeeding is responsible for approximately 300,000 HIV infections per year, while at the same time, UNICEF estimates that not breastfeeding (formula feeding with contaminated water) is responsible for 1.5 million child deaths per year. The largest burden of these infections and deaths occur in Sub-Saharan Africa. Using this region as an example of the burden faced more generally in other resource-poor settings, we contrast the evolution of the clinical standard of care for infant feeding with HIV-infected mothers in high-income countries to the current international clinical guidelines for HIV-infected mothers and infant feeding in resource-poor settings. While the international guidelines of exclusive breastfeeding for a 6-month period seem to offer the least-worst strategy for reducing mother-to-child transmission of HIV during infancy while conferring some immunity through breastfeeding post-6 months, we argue that the impact of the policy on mothers and healthcare workers on the ground is not well understood. The harm reduction approach on the level of health policy translates into a complicated, painful moral dilemma for HIV-positive mothers and those offering them guidance on infant feeding. We argue that the underlying socio-economic disparities that continue to fuel the need for a harm reduction policy on infant feeding and the harm to women and children justify: (1) that higher priority be given to solving the infant feeding dilemma with improved data on safe feeding alternatives, and (2) support of innovative, community-driven solutions that address the particular economic and cultural challenges that continue to result in HIV-transmission to children within these communities.


A comparison of three tumescent delivery systems in endovenous laser ablation of the great saphenous vein.
Different systems for delivering tumescent solution exist in endovenous laser ablation (EVLA). This study evaluated three different tumescent delivery systems in patients with primary varicose veins due to great saphenous vein reflux who were treated with EVLA. In this prospective non-randomized study, 60 patients with isolated GSV varicose veins were divided into three groups. All patients received EVLA treatment. Three different tumescent solution delivery systems were used. Systems consisted of a needle and a syringe in Group 1, a needle connected to an infusion bag system in Group 2 and a peristaltic infiltration pump in Group 3. Tumescent delivery durations were in Group 1: 6.56 SD 1.18 minutes, Group 2: 6.05 SD 2.19 minutes and Group 3: 5.19 SD 1.15 minutes (P = 0.014). In the outcomes of the study there were no significant difference between groups. Although peristaltic pump systems might provide shorter tumescent delivery durations without hand fatigue, shorter duration does not have any practical importance (about 1 minute and also it is not cost-effective. For delivering tumescent solutions in EVLA procedures, there was no major superiority between systems.


Temporal strategy and performance during a fatiguing short-cycle repetitive task.
This study investigated temporal changes in movement strategy and performance during fatiguing short-cycle work. Eighteen participants performed six 7-min work blocks with repetitive reaching movements at 0.5 Hz, each followed by a 5.5-min rest break for a total duration of 1 h. Electromyography (EMG) was collected continuously from the upper trapezius muscle, the temporal movement strategy and timing errors were obtained on a cycle-to-cycle basis, and perceived fatigue was rated before and after each work block. Clear signs of fatigue according to subjective ratings and EMG manifestations developed within each work block, as well as during the entire hour. For most participants, timing errors gradually increased, as did the waiting time at the near target. Changes in temporal movement strategy were negatively correlated with changes in the level and variability of EMG, suggesting that an adaptive temporal strategy offset the development of unstable motor solutions in this fatiguing, short-cycle work. Sustained performance of operators is essential to maintain competitiveness. In this study of repetitive work, participants gradually changed their temporal movement strategy, for possibly alleviating the effects of fatigue. This suggests that in order to effectively counteract fatigue and sustain performance, industrial production should allow extensive spatial and temporal flexibility.


Characterization of polypeptides in Rickettsia tsutsugamushi: effect of preparative conditions on migration of polypeptides in polyacrylamide gel electrophoresis.
The polypeptide compositions and antigenic components of Rickettsia tsutsugamushi were analyzed by modifying the solubilization conditions prior to polyacrylamide gel electrophoresis and by using monoclonal antibodies in immunoblotting experiments. Several polypeptides were converted to larger or smaller molecules by using various conditions for rickettsial sample preparation. Solubilization of a sample in 2-mercaptoethanol-containing buffer resulted in conversion of high-molecular-weight polypeptides to smaller polypeptides and conversion of some of the 43-kilodalton (43K) polypeptide to a 46K polypeptide. The heat modifiability of selected polypeptides was shown by heating samples at 100 degrees C. A major polypeptide on the rickettsial surface which showed strain-specific antigenicity appeared at the 43K position in samples solubilized at 37 degrees C but moved to the 56K position after samples were heated at 100 degrees C. Immunoblotting with an anti-56K polypeptide monoclonal antibody demonstrated that the reactive antigens existed predominantly as the higher-molecular-weight polypeptides. These polypeptides were converted to 43K polypeptides at 37 degrees C or the 56K polypeptides at 100 degrees C by cleavage of disulfide linkages with 2-mercaptoethanol treatment.


HIV transmissions during seroconversion contribute significantly to new infections in men who have sex with men in Australia.
Transmission of HIV from recently infected individuals contributes to the number of new cases of infection, but the extent to which it occurs from those who are unaware of their infection is not known. Phylogenetic analysis was performed on 209 cases of acute HIV subtype B infection detected between January 2005 and September 2010, most of whom (88%) were men who have sex with men. Only new cases with an evolving Western blot profile confirmed by detection of HIV RNA were included. Subjects whose known dates of seroconversion were within 1 month of at least one other phylogenetically linked case identified during the 6 years of the study were then examined to estimate the prevalence of onward transmission. Almost 30% of cases could have acquired their infection from another person undergoing seroconversion within the same month. Temporal increases in the number of phylogenetically related strains within several clusters were demonstrated during the study, although the rate of increase varied. Transmission of HIV from individuals undergoing seroconversion is an important contributor to the number of new infections identified every year and very likely occurs before they have knowledge of their infection. Clusters of related HIV strains can grow at a disconcerting rate, demonstrating that more focused public health efforts are required to minimize further HIV transmissions within sexual networks.


Cyclosporine challenge in the decision of combined kidney-pancreas versus solitary pancreas transplantation.
Combined kidney-pancreas transplantation has become the treatment of choice for many patients with end-stage diabetic nephropathy. Pancreas transplantation (PTx) alone is an option for type I diabetic patients without end-stage diabetic nephropathy. Knowledge of factors contributing to or predicting the rate of renal deterioration (including the effect of CsA on the patient's renal function before transplantation) is necessary to determine candidacy for either kidney-pancreas transplantation or PTx alone. To address this issue, we selected 12 pre-uremic patients with creatinine clearances (CrCl) above 40 ml/min and less than 100 ml/min to participate in a 6-week oral CsA challenge test. Serum chemistries, including serum creatinine (SCr) and CsA level, were measured weekly. Urinary protein and CrCl were measured at 0, 2, 4, and 6 weeks. Glomerular filtration rate (GFR) (by 125I-sodium iothalamate clearance) was measured at 0, 3, and 6 weeks. All patients initially received oral CsA at 10 mg/kg/day in 2 divided doses. Doses were adjusted to maintain a 12-hr trough level of 500-1000 ng/ml using a whole blood polyclonal TDX assay. Data are presented as mean +/- SEM and as box-plot graphs. One patient was a CsA challenge test failure because SCr exceeded 3.0 mg/dl despite a reduction in CsA dose and level. Therefore, this patient was not a candidate for PTx alone and was excluded from further analysis. Among the 11 nonfailures, the mean CsA level at 6 weeks was 640 +/- 76 ng/ml. SCr increased from 1.2 +/- 0.1 mg/dl to 1.6 +/- 0.1 mg/dl (33% increase) (P = 0.0001). CrCl decreased from 82 +/- 9 ml/min to 63 +/- 8 ml/min (24% decrease) (P = 0.03). GFR decreased from 95 +/- 15 ml/min to 70 +/- 10 ml/min (26% decrease) (P = 0.009). CrCl and GFR did not differ from one another at 0 and 6 weeks (r = 0.77 and 0.98; P = 0.3 and 0.7, respectively). Urinary protein decreased from 1.0 +/- 0.3 g/day to 0.7 +/- 0.3 g/day at both 4 and 6 weeks (P = 0.03 and 0.06, respectively). Three of the 11 patients have not yet received transplants. Eight patients subsequently received PTx alone and were followed prospectively. Two allografts were lost early to rejection. Six were followed from 5 to 19 months after PTx alone. Serum creatinine and CrCL measurements during the CsA challenge test predicted post-PTx levels: SCr 1.6 +/- 0.1 vs. 1.7 +/- 0.3 mg/dl, P = 0.48, and CrCl 68 +/- 10 vs. 53 +/- 3 ml/min, P = 0.17, respectively.


Environmentally-induced parental or developmental conditioning influences coral offspring ecological performance.
The persistence of reef building corals is threatened by human-induced environmental change. Maintaining coral reefs into the future requires not only the survival of adults, but also the influx of recruits to promote genetic diversity and retain cover following adult mortality. Few studies examine the linkages among multiple life stages of corals, despite a growing knowledge of carryover effects in other systems. We provide a novel test of coral parental conditioning to ocean acidification (OA) and tracking of offspring for 6 months post-release to better understand parental or developmental priming impacts on the processes of offspring recruitment and growth. Coral planulation was tracked for 3 months following adult exposure to high pCO2 and offspring from the second month were reciprocally exposed to ambient and high pCO2 for an additional 6 months. Offspring of parents exposed to high pCO2 had greater settlement and survivorship immediately following release, retained survivorship benefits during 1 and 6 months of continued exposure, and further displayed growth benefits to at least 1 month post release. Enhanced performance of offspring from parents exposed to high conditions was maintained despite the survivorship in both treatments declining in continued exposure to OA. Conditioning of the adults while they brood their larvae, or developmental acclimation of the larvae inside the adult polyps, may provide a form of hormetic conditioning, or environmental priming that elicits stimulatory effects. Defining mechanisms of positive acclimatization, with potential implications for carry over effects, cross-generational plasticity, and multi-generational plasticity, is critical to better understanding ecological and evolutionary dynamics of corals under regimes of increasing environmental disturbance. Considering environmentally-induced parental or developmental legacies in ecological and evolutionary projections may better account for coral reef response to the chronic stress regimes characteristic of climate change.


Dirac cone in α-graphdiyne: a first-principles study.
: We investigate the Dirac cone in α-graphdiyne, which is a predicted flat one-atom-thick allotrope of carbon using first-principles calculations. α-graphdiyne is derived from graphene where two acetylenic linkages (-C ≡C-) are inserted into the single bonds (-C-C-). Thus, α-graphdiyne possesses a larger lattice constant which subsequently affects its electronic properties. Band structures show that α-graphdiyne exhibits similar Dirac points and cone to graphene. Further, the tight-binding method is used to exploit the linear dispersion in the vicinity of Dirac points. Thanks to the larger lattice constant, α-graphdiyne yields a lower Fermi velocity, which might make itself an ideal material to serve the anomalous integer quantum Hall effect.


Intrinsic DNA Shape Accounts for Affinity Differences between Hox-Cofactor Binding Sites.
Transcription factors bind to their binding sites over a wide range of affinities, yet how differences in affinity are encoded in DNA sequences is not well understood. Here, we report X-ray crystal structures of four heterodimers of the Hox protein AbdominalB bound with its cofactor Extradenticle to four target DNA molecules that differ in affinity by up to ∼20-fold. Remarkably, despite large differences in affinity, the overall structures are very similar in all four complexes. In contrast, the predicted shapes of the DNA binding sites (i.e., the intrinsic DNA shape) in the absence of bound protein are strikingly different from each other and correlate with affinity: binding sites that must change conformations upon protein binding have lower affinities than binding sites that have more optimal conformations prior to binding. Together, these observations suggest that intrinsic differences in DNA shape provide a robust mechanism for modulating affinity without affecting other protein-DNA interactions.


Long-term clinical outcomes of surgery for adolescent idiopathic scoliosis 21 to 41 years later.
A case control study. To determine the clinical outcome of middle-aged patients surgically treated for adolescent idiopathic scoliosis and to compare their outcomes with assessments of age- and sex-matched healthy controls. Several long-term follow-up studies have been published on the clinical outcomes of surgical treatment for adolescent idiopathic scoliosis in patients who have reached their 20s or 30s. However, clinical outcomes in patients who have reached middle age remain unknown. This study included 256 patients surgically treated for adolescent idiopathic scoliosis (AIS) between 1968 and 1988. The Scoliosis Research Society Patient Questionnaire (SRS-22) and Roland-Morris Disability Questionnaire (RDQ) were used for evaluating long-term clinical outcomes. Sixty-six (25.8%; 62 females, 4 males; mean age, 46.0 years [range 34-56]) of the 256 patients responded to the questionnaires. The mean follow-up period was 31.5 (range 21-41) years. Seventy-six healthy age- and sex-matched individuals with neither a history of spinal surgery nor scoliosis were selected as a control (CTR) group. On the basis of the SRS-22 responses, AIS patients had significantly decreased function (AIS: 4.3 ± 0.6, CTR: 4.7 ± 0.5, P < 0.01) and decreased self-image (AIS: 3.0 ± 0.8, CTR: 3.7 ± 0.5, P < 0.01) in comparison with the controls, but the 2 groups were similar with respect to pain (AIS: 4.3 ± 0.6, CTR: 4.2 ± 0.5, P = 0.14) and mental health (AIS: 3.9 ± 0.9, CTR: 3.7 ± 0.7, P = 0.14). The RDQ responses indicated that low back pain was not significantly increased in the AIS group compared with the CTR group (AIS: 1.8 ± 3.5, CTR: 1.4 ± 3.1, P = 0.36). Surgery had no demonstrable adverse effects on pain or mental health in these middle-aged AIS patients 21-41 years after surgery, although the AIS patients did have significantly lower function and lower self-image than the controls.


Systematic mapping of cell wall mechanics in the regulation of cell morphogenesis.
Walled cells of plants, fungi, and bacteria come with a large range of shapes and sizes, which are ultimately dictated by the mechanics of their cell wall. This stiff and thin polymeric layer encases the plasma membrane and protects the cells mechanically by opposing large turgor pressure derived mechanical stresses. To date, however, we still lack a quantitative understanding for how local and/or global mechanical properties of the wall support cell morphogenesis. Here, we combine subresolution imaging and laser-mediated wall relaxation to quantitate subcellular values of wall thickness (h) and bulk elastic moduli (Y) in large populations of live mutant cells and in conditions affecting cell diameter in the rod-shaped model fission yeast. We find that lateral wall stiffness, defined by the surface modulus, σ = hY, robustly scales with cell diameter. This scaling is valid across tens of mutants spanning various functions-within the population of individual isogenic strains, along single misshaped cells, and even across the fission yeasts clade. Dynamic modulations of cell diameter by chemical and/or mechanical means suggest that the cell wall can rapidly adapt its surface mechanics, rendering stretched wall portions stiffer than unstretched ones. Size-dependent wall stiffening constrains diameter definition and limits size variations; it may also provide an efficient means to keep elastic strains in the wall below failure strains, potentially promoting cell survival. This quantitative set of data impacts our current understanding of the mechanics of cell walls and its contribution to morphogenesis.


Effect of statin use on acute kidney injury risk following coronary artery bypass grafting.
Acute kidney injury (AKI) is a serious complication of cardiovascular surgery. Although some nonexperimental studies suggest that statin use may reduce postsurgical AKI, methodologic differences in study designs leave uncertainty regarding the reality or magnitude of the effect. The aim of this study was to estimate the effect of preoperative statin initiation on AKI after coronary artery bypass grafting (CABG) using an epidemiologic approach more closely simulating a randomized controlled trial in a large CABG patient population. Health care claims from large, employer-based and Medicare insurance databases for 2000 to 2010 were used. To minimize healthy user bias, patients were identified who underwent nonemergent CABG who either newly initiated a statin <20 days before surgery or were unexposed for ≥200 days before CABG. AKI was identified <15 days after CABG. Multivariate-adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using Poisson regression. Analyses were repeated using propensity score methods adjusted for clinical and health care utilization variables. A total of 17,077 CABG patients were identified. Post-CABG AKI developed in 3.4% of statin initiators and 6.2% of noninitiators. After adjustment, a protective effect of statin initiation on AKI was observed (RR 0.78, 95% CI 0.63 to 0.96). This effect differed by age, with an RR of 0.91 (95% CI 0.68 to 1.20) for patients aged ≥65 years and an RR of 0.62 (95% CI 0.45 to 0.86) for those aged <65 years, although AKI was more common in the older group (7.7% vs 4.0%). In conclusion, statin initiation immediately before CABG may modestly reduce the risk for postoperative AKI, particularly in younger CABG patients.


Could parental rules play a role in the association between short sleep and obesity in young children?
Short sleep duration is associated with obesity in young children. This study develops the hypothesis that parental rules play a role in this association. Participants were 3-year-old children and their parents, recruited at nursery schools in socioeconomically deprived and non-deprived areas of a North-East England town. Parents were interviewed to assess their use of sleep, television-viewing and dietary rules, and given diaries to document their child's sleep for 4 days/5 nights. Children were measured for height, weight, waist circumference and triceps and subscapular skinfold thicknesses. One-hundred and eight families participated (84 with complete sleep data and 96 with complete body composition data). Parental rules were significantly associated together, were associated with longer night-time sleep and were more prevalent in the non-deprived-area compared with the deprived-area group. Television-viewing and dietary rules were associated with leaner body composition. Parental rules may in part confound the association between night-time sleep duration and obesity in young children, as rules cluster together across behavioural domains and are associated with both sleep duration and body composition. This hypothesis should be tested rigorously in large representative samples.


Assessment of Parents'/Guardians' Initial Comprehension and 1-Day Recall of Elements of Informed Consent Within a Mozambican Study of Pediatric Bacteremia.
Participants' understanding of key elements of a research protocol is essential to their ethical enrollment in the study. Ongoing participation should be based on continued comprehension and consent, which presumes a high degree of recall. Many obstacles can prevent full understanding of information about the research protocol. This study's aim was to evaluate the comprehension and 1-day recall of the elements of informed consent by the parents/guardians of children enrolled in a clinical study in Mozambique. We developed a 10-question test based on the study's informed consent document. We asked participants to answer questions shortly after being read the informed consent document and again the following day. Participants who did not demonstrate good or reasonable understanding at enrollment were provided the information again as a refresher. Overall high rates of initial comprehension demonstrate that attention to the informed consent process can result in Mozambicans' informed, voluntary participation in clinical trials.


TELS: A Novel Computational Framework for Identifying Motif Signatures of Transcribed Enhancers.
In mammalian cells, transcribed enhancers (TrEns) play important roles in the initiation of gene expression and maintenance of gene expression levels in a spatiotemporal manner. One of the most challenging questions is how the genomic characteristics of enhancers relate to enhancer activities. To date, only a limited number of enhancer sequence characteristics have been investigated, leaving space for exploring the enhancers' DNA code in a more systematic way. To address this problem, we developed a novel computational framework, Transcribed Enhancer Landscape Search (TELS), aimed at identifying predictive cell type/tissue-specific motif signatures of TrEns. As a case study, we used TELS to compile a comprehensive catalog of motif signatures for all known TrEns identified by the FANTOM5 consortium across 112 human primary cells and tissues. Our results confirm that combinations of different short motifs characterize in an optimized manner cell type/tissue-specific TrEns. Our study is the first to report combinations of motifs that maximize classification performance of TrEns exclusively transcribed in one cell type/tissue from TrEns exclusively transcribed in different cell types/tissues. Moreover, we also report 31 motif signatures predictive of enhancers' broad activity. TELS codes and material are publicly available at http://www.cbrc.kaust.edu.sa/TELS.


Short-term appetite control in response to a 6-week exercise programme in sedentary volunteers.
Previous cross-sectional studies have shown that sedentary males, unlike their active counterparts, are unable to compensate for previous energy intake (EI). The present study therefore investigated the effects of a 6-week moderate exercise programme (4 times per week, 65-75 % maximal heart rate) on appetite regulation in healthy sedentary volunteers using a longitudinal design. EI at a buffet meal 60 min after high-energy (HEP; 607 kcal) and low-energy (LEP; 246 kcal) preloads, together with 24 h cumulative EI, were measured in twenty-five healthy volunteers (eleven men; mean age 30 (SD 12) years, mean BMI 22.7 (SD 2.3) kg/m2), at baseline and after the exercise intervention. Subjective hunger and fullness were assessed throughout using visual analogue scales. ANOVA showed a significant preload x exercise interaction on 24 h cumulative EI, supporting an improvement in appetite control over this time period with the exercise programme. There was a trend towards improvement in energy compensation over the same period (8.9 (SD 118.5) % v. 79.5 (SD 146..4) %; P = 0.056). No preload x exercise interaction was observed for buffet EI. Secondary analysis, however, showed that although buffet EI after the two preloads was not significantly different at baseline, buffet EI after the HEP was significantly lower than after the LEP following the exercise intervention. The improvement in short-term appetite control with exercise was not explained by changes in subjective hunger or satiety. This longitudinal study supports the original cross-sectional findings and suggests that exercise may have a significant impact on short-term appetite control by leading to a more sensitive eating behaviour in response to previous EI. Further studies are needed to clarify the mechanisms involved.


A rapid method of diagnosing pulmonary tuberculosis using stir bar sorptive extraction-thermal desorption-gas chromatography-mass spectrometry.
A fast method for detection of tuberculostearic acid (TBSA) in sputum samples is described. The samples, obtained from patients with known or suspected pulmonary tuberculosis, were decontaminated and concentrated before being analyzed by stir bar sorptive extraction-thermal desorption-gas chromatography-mass spectrometry (SBSE-TD-GC-MS). Prior to extraction, the mycobacterial lipids were hydrolyzed and then derivatized with ethyl chloroformate to increase the sorption of the compounds by the polydimethylsiloxane (PDMS) stir bar coating. The limit of detection (LOD) is 0.2 ng ml(-1). Four sputum samples that were classified by direct microscopy as smear-positive or negative were analyzed by GC-MS. TBSA was detected at concentrations ranging from 0.47 to 2.3 ng ml(-1). The method is sufficiently sensitive to detect TBSA directly in clinical samples without the need to culture the organisms.


Carney complex (CNC).
The Carney complex (CNC) is a dominantly inherited syndrome characterized by spotty skin pigmentation, endocrine overactivity and myxomas. Skin pigmentation anomalies include lentigines and blue naevi. The most common endocrine gland manifestations are acromegaly, thyroid and testicular tumors, and adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). PPNAD, a rare cause of Cushing's syndrome, is due to primary bilateral adrenal defect that can be also observed in some patients without other CNC manifestations or familial history of the disease. Myxomas can be observed in the heart, skin and breast. Cardiac myxomas can develop in any cardiac chamber and may be multiple. One of the putative CNC genes located on 17q22-24, (PRKAR1A), has been identified to encode the regulatory subunit (R1A) of protein kinase A. Heterozygous inactivating mutations of PRKAR1A were reported initially in 45 to 65% of CNC index cases, and may be present in about 80% of the CNC families presenting mainly with Cushing's syndrome. PRKAR1A is a key component of the cAMP signaling pathway that has been implicated in endocrine tumorigenesis and could, at least partly, function as a tumor suppressor gene. Genetic analysis should be proposed to all CNC index cases. Patients with CNC or with a genetic predisposition to CNC should have regular screening for manifestations of the disease. Clinical work-up for all the manifestations of CNC should be performed at least once a year in all patients and should start in infancy. Cardiac myxomas require surgical removal. Treatment of the other manifestations of CNC should be discussed and may include follow-up, surgery, or medical treatment depending on the location of the tumor, its size, the existence of clinical signs of tumor mass or hormonal excess, and the suspicion of malignancy. Bilateral adrenalectomy is the most common treatment for Cushing's syndrome due to PPNAD.


Hematology and Productive Performance of Nile Tilapia (Oreochromis niloticus) Naturally Infected With Flavobacterium columnare.
Columnaris disease is one of the main causes of mortality in tilapia rearing and is responsible for large economic losses worldwide. Hematology is a tool that makes it possible to study organisms' physiological responses to pathogens. It may assist in making diagnoses and prognoses on diseases in fish populations. The hematological variables of nile tilapia were studied in specimens with a clinical diagnosis of columnaris disease and in specimens that were disease-free. The total erythrocyte count, hemoglobin rate, hematocrit percentage, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), organic defense blood cell percentages (leukocytes and thrombocytes) and hepatosomatic and splenosomatic index were determined. The results showed that there were changes in the erythrocytic series and in organic defense blood cells, in the fish infected with the bacterium, with reductions in erythrocytic variables and significant increases in the numbers of circulating lymphocytes and neutrophils.


[Study of celiac disease in the pediatric population of Cantabria (Spain) and first-degree relatives].
Celiac disease (CD) is an autoimmune disease that affects genetically predisposed individuals. The HLA-DQ2 heterodimer is present in nearly 90% of patients while HLA-DQ8 is found in the remaining 10%. To study the characteristics of CD in pediatric patients in Cantabria and their first-degree relatives, with special emphasis on factors related to haplotype, serology, and forms of clinical presentation. Eighty-six patients with CD and 215 first-degree relatives were HLA genotyped. Clinical, laboratory, immunologic, and histological data were obtained from all patients. Clinical presentation was classical in 95% of the patients and mono-symptomatic in the remaining 5%. Anti-gliadin antibodies (AGA) and anti-transglutaminase antibodies (ATGA) were positive in 95% of the patients and negative in 5% (all with IgA deficiency). DQ2 was found in 71% of the patients (homozygotes or heterozygotes) and DQ8 was found in 9.5%. No heterodimers of risk were found in 22%. CD was found in six relatives (three were positive for AGA and four were positive for ATGA). Forty-nine percent of the relatives carried the DQ2 heterodimer and 15% the DQ8 heterodimer; no heterodimers of risk were found in 40%. The most prevalent HLA found in patients with CD in the autonomous region of Cantabria was DQ2 (71%). This prevalence is clearly lower than that reported in other Spanish regions. The prevalence of CD among first-degree relatives was similar to that found in other studies performed in Spain (2.8%). Our data support the need for systematic study of the first-degree relatives of patients with CD.


Influence of structural variations in push-pull zinc porphyrins on photovoltaic performance of dye-sensitized solar cells.
We designed and synthesized two new zinc porphyrin dyes for dye-sensitized solar cells (DSCs). Subtle molecular structural variation in the dyes significantly influenced the performance of the DSC devices. By utilizing these dyes in combination with a cobalt-based redox electrolyte using a photoanode made of mesoporous TiO2 , we achieved a power conversion efficiency (PCE) of up to 12.0 % under AM 1.5 G (100 mW cm(-2)) simulated solar light. Moreover, we obtained a high PCE of 6.4 % for solid-state dye-sensitized solar cells by using 2,2',7,7'-tetrakis-(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene as a hole-transporting material.


Greener neighbourhoods, better memory? A longitudinal study.
Urban green space may help slow cognitive decline. We extend the investigation towards subjective memory and green space type using latent class analysis and multilevel models of 45,644 individuals in the Sax Institute's 45 and Up Study. Participants with more tree canopy relative to open grass within 1.6 km, compared to similar quantities of both types, tended to have more favourable odds of subjective memory complaints and self-rated excellent memory at baseline. Higher quantities of open grass relative to tree canopy did not afford similar levels of benefit. Socioeconomic factors explained associations between green space and cumulative incidence of memory-related outcomes.


The axr2-1 mutation of Arabidopsis thaliana is a gain-of-function mutation that disrupts an early step in auxin response.
The dominant axr2-1 mutation of Arabidopsis thaliana confers resistance to the plant hormones auxin, ethylene, and abscisic acid. In addition, axr2-1 has pleiotropic effects on plant morphology which include gravitropic defects in roots, hypocotyls and inflorescences of axr2-1 plants. Two genetic screens were conducted to isolate new mutations at the AXR2 locus. First, axr2-1 pollen was gamma-irradiated, crossed onto wild-type plants, and the M1 progeny screened for loss of the axr2-1 phenotype. Large deletions of the axr2-1 region on chromosome 3 resulted; however, none of these deletions appeared to be heritable. In the second, M2 seed obtained from axr2-1 gl-1 plants was screened for reversion of the axr2-1 phenotype. One revertant line, axr2-r3, has a distinctive phenotype caused by a second mutation at the axr2 locus. To learn more about the nature of the axr2-1 mutation, the effects of varying the ratio of wild-type to mutant copies of the AXR2 gene were examined by comparing plants of the following genotypes: +/+, +/+/+, axr2-1/axr2-1, axr2-1/+ and axr2-1/+/+. Additionally, accumulation of transcripts from the auxin-inducible SAUR-AC1 gene was examined to determine the response of wild-type and mutant plants to auxin. Wild-type seedlings and mature plants accumulate transcripts with auxin treatment. In contrast, axr2-1 tissue does not accumulate SAUR-AC1 transcripts in response to auxin. Taken together, these results indicate that axr2-1 is a neomorphic or hypermorphic mutation that disrupts an early step in an auxin response pathway.


Primary care spirometry.
Primary care spirometry is a uniquely valuable tool in the evaluation of patients with respiratory symptoms, allowing the general practitioner to diagnose or exclude chronic obstructive pulmonary disease (COPD), sometimes to confirm asthma, to determine the efficacy of asthma treatment and to correctly stage patients with COPD. The use of spirometry for case finding in asymptomatic COPD patients might become an option, once early intervention studies have shown it to be beneficial in these patients. The diagnosis of airway obstruction requires accurate and reproducible spirometric measurements, which should comply with the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines. Low acceptability of spirometric manoeuvres has been reported in primary care practices. This may hamper the validity of the results and affect clinical decision making. Training and refresher courses may produce and maintain good-quality testing, promote the use of spirometric results in clinical practice and enhance the quality of interpretation. Softening the stringent ATS/ERS criteria could enhance the acceptability rates of spirometry when used in a general practice. However, the implications of potential simplifications on the quality of the data and clinical decision making remain to be investigated. Hand-held office spirometers have been developed in recent years, with a global quality and user-friendliness that makes them acceptable for use in general practices. The precision of the forced vital capacity measurements could be improved in some of the available models.


Primary souring: A novel bacteria-free method for sour beer production.
In the beverage fermentation industry, especially at the craft or micro level, there is a movement to incorporate as many local ingredients as possible to both capture terroir and stimulate local economies. In the case of craft beer, this has traditionally only encompassed locally sourced barley, hops, and other agricultural adjuncts. The identification and use of novel yeasts in brewing lags behind. We sought to bridge this gap by bio-prospecting for wild yeasts, with a focus on the American Midwest. We isolated 284 different strains from 54 species of yeast and have begun to determine their fermentation characteristics. During this work, we found several isolates of five species that produce lactic acid and ethanol during wort fermentation: Hanseniaspora vineae, Lachancea fermentati, Lachancea thermotolerans, Schizosaccharomyces japonicus, and Wickerhamomyces anomalus. Tested representatives of these species yielded excellent attenuation, lactic acid production, and sensory characteristics, positioning them as viable alternatives to lactic acid bacteria (LAB) for the production of sour beers. Indeed, we suggest a new LAB-free paradigm for sour beer production that we term "primary souring" because the lactic acid production and resultant pH decrease occurs during primary fermentation, as opposed to kettle souring or souring via mixed culture fermentation.


In vivo exercise followed by in vitro contraction additively elevates subsequent insulin-stimulated glucose transport by rat skeletal muscle.
The cellular mechanisms whereby prior exercise enhances insulin-stimulated glucose transport (GT) are not well understood. Previous studies suggested that a prolonged increase in phosphorylation of Akt substrate of 160 kDa (AS160) may be important for the postexercise increase in insulin sensitivity. In the current study, the effects of in vivo exercise and in vitro contraction on subsequent insulin-stimulated GT were studied separately and together. Consistent with results from previous studies, prior exercise resulted in an increase in AS160 (642)Thr phosphorylation immediately after exercise in rat epitrochlearis muscles, and this increase remained 3 h postexercise concomitant with enhanced insulin-stimulated GT. For experiments with in vitro contraction, isolated rat epitrochlearis muscles were electrically stimulated to contract in the presence or absence of rat serum. As expected, insulin-stimulated GT measured 3 h after electrical stimulation in serum, but not after electrical stimulation without serum, exceeded resting controls. Immediately after electrical stimulation with or without serum, phosphorylation of both AS160 (detected by phospho-Akt substrate, PAS, antibody, or phospho-(642)Thr antibody) and its paralog TBC1D1 (detected by phospho-(237)Ser antibody) was increased. However, both AS160 and TBC1D1 phosphorylation had reversed to resting values at 3 h poststimulation with or without serum. Increasing the amount of exercise (from 1 to 2 h) or electrical stimulation (from 5 to 10 tetani) did not further elevate insulin-stimulated GT. In contrast, the combination of prior exercise and electrical stimulation had an additive effect on the subsequent increase in insulin-stimulated GT, suggesting that these exercise and electrical stimulation protocols may amplify insulin-stimulated GT through distinct mechanisms, with a persistent increase in AS160 phosphorylation potentially important for increased insulin sensitivity after exercise, but not after in vitro contraction.


Ciliate protozoa of the forestomach of llamas (Lama glama) from locations <br />at different altitude in Argentina.
This study describes the diversity and concentration of the protozoal population from the forestomach of llamas in Argentina at three altitudinal locations. Protozoal diversity was studied in samples from eight llamas from Hurlingham (Buenos Aires, 43 m altitude), four from Tilcara (Jujuy, 2465 m altitude) and six llamas from Cieneguillas (Jujuy, 3800 m altitude). The total concentrations of protozoa in the forestomach contents were 7.9, 9.1 and 4.1 cells x 104 ml-1 in Hurlingham, Tilcara and Cieneguillas, respectively (P>0.05). Entodinium spp. represented 97.9, 92.3 and 71.4% of the protozoal community in Hurlingham, Tilcara and Cieneguillas, respectively, and the remaining protozoa belonged to the Eudiplodinium genus. Entodinium spp. were identified as E. caudatum (mostly morphotype dubardi), E. longinucleatum, E. parvum, E. bovis, E. exiguum, E. dubardi, and a minor presence of E. bimastus (in three animals) and E. ovibos (in one animal). In regards to the rest of protozoal species, Eudiplodinium maggii is the first reported host record for the genus in llamas. This species was present in the forestomach of 14 out of 18 llamas tested, and in one case it was the unique protozoal species. The vestibuliferids, Dasytricha and Isotricha were absent from the forestomach of llamas. Similarly, other species such as those from the Caloscolex genus, Diplodinium cameli and Entodinium ovumrajae, commonly found in Old World Camelids, were also absent from llamas.


Design of a molecular imprinting biosensor with multi-scale roughness for detection across a broad spectrum of biomolecules.
The molecular imprinting technique has tremendous applications in artificial enzymes, bioseparation, and sensor devices. In this study, a novel molecular imprinting (MI) biosensor platform was developed for the detection of a broad range of biomolecules with different sizes. Previously this method has been applied to 2D molecular imprinting, where the height of the self-assembled monolayer (SAM) of around 2 nm limited the maximum dimensions of the molecule that can be imprinted to create template-shaped cavities. In order to match the size of the imprinted molecules with the height of the SAM, we propose a model for 3D molecular imprinting where the analyte is sequestered within a niche created by the surface roughness. The SAM is assembled on the walls of the niche, forming a 3D pattern of the analyte uniquely molded to its contour. Surfaces with multi-scale roughness were prepared by evaporation of gold onto electropolished (smooth) and unpolished (rough) Si wafers, where the native roughness was found to have a normal distribution centered around 5 and 90 nm respectively. Our studies using molecules with size ranging on a nanometer scale, from proteins of a few nanometers to bacteria of hundreds of nanometers, showed that when the size of the analyte matched the roughness range of the gold surface, the molecular imprinting process was optimized for the best biosensing performance. After optimization, the MI biosensor platform enabled the identification and quantification of a broad range of biomolecules with great discrimination abilities. Hemoglobin under different pH values and several mutated fibrinogen molecules can also be well differentiated through the test.


Epicatechin conjugated with fatty acid is a potent inhibitor of DNA polymerase and angiogenesis.
Anti-cancer and anti-angiogenesis effects of green tea catechins have been demonstrated. It has been found that chemical modification of tea catechins improves their biological activities. We examined the chemical modification of epicatechin enhanced anti-cancer and anti-angiogenic effects. Epicatechin conjugated with fatty acid (acyl-catechin) strongly inhibited DNA polymerase activity, HL-60 cancer cell growth and angiogenesis. Epicatechin conjugated with palmitic acid ((2R,3R)-3',4',5,7-tetrahydroxyflavan-3-yl hexadecanoate, epicatechin-C16) was the strongest inhibitor in DNA polymerase alpha, beta, lambda and angiogenesis assays. Epicatechin-C16 also suppressed human endothelial cell (HUVEC) tube formation on reconstituted basement membrane, suggesting that it affected not only DNA polymerase activity but also the signal transduction pathways needed for the tube formation in HUVECs. These results suggest that acylation of epicatechin is an effective chemical modification to improve the anti-cancer activity of epicatechin.


Probabilistic record linkage for monitoring the safety of artemisinin-based combination therapy in the first trimester of pregnancy in Senegal.
There are insufficient data on the safety in early pregnancy of the artemisinins, a new class of antimalarials. Assessment of drug teratogenicity requires large sample sizes for an adequate risk-benefit assessment. There is currently limited pharmacovigilance infrastructure in malaria-endemic countries. Monitoring drug safety in early pregnancy is especially challenging, as it requires early pregnancy detection to assess any potential increased risk of miscarriage, prospective follow-up to reduce recall and survival biases, and accurate data on gestational age assessment. Record linkage approaches for pregnancy pharmacovigilance using routinely generated health records could be a pragmatic and cost-effective approach for pharmacovigilance in early pregnancy, but has not been evaluated in resource-poor settings. Our objective was to assess the feasibility of record linkage using routinely collected healthcare data as a pragmatic means of monitoring the safety in early pregnancy of artemisinin-based combination therapies (ACTs) in Senegal. Data (2004-2008) from paper-based registers from outpatient clinics, antenatal care services (ANC) and the delivery unit from the St Joseph dispensary in Mlomp, south-western Senegal, were entered into databases. Record linkage based on a probabilistic matching approach was used to identify pregnancies exposed to ACTs in the first trimester of pregnancy. Two record linkage software packages (Link-Plus and FRIL) were compared and output data were reviewed independently by two investigators. Information on 685 pregnancies was extracted, 536 of which were from the geographic catchment area and eligible for record linkage; 94.6 % of them resulted in live births, 2.6 % in stillbirths and 2.8 % in miscarriages. Major congenital malformations were identified in 1.6 % of births. Seventy-three and 75 true matches between pregnancy outcome and the outpatient treatment registers were identified by two different record linkage software packages, respectively. Record linkage identified seven exposures to ACTs in the first trimester, all of which resulted in normal live-births. Probabilistic record linkage is a potentially cost-effective method to assess the safety of antimalarials in early pregnancy in resource-constrained settings to assess increased risk of overall birth defects, and stillbirths in settings with good existing health records and well defined target populations.


Fluconazole nasal spray in the treatment of allergic fungal sinusitis: a pilot study.
The authors describe a prospective pilot study designed to investigate the use of topical nasal antifungal spray in addition to systemic steroids and itraconazole in the treatment of allergic fungal sinusitis. Sixteen patients with a history of allergic fungal sinusitis were given fluconazole nasal spray and followed for 3 months. Stabilization or improvement of disease without significant side effects was observed in 12 of the 16 patients who were treated with this protocol. These results indicate that topical fluconazole application may help patients with allergic fungal sinusitis; however, a larger multicenter study with longer patient follow-up is required to validate these initial findings.


A versatile platform for the highly efficient preparation of graphene quantum dots: photoluminescence emission and hydrophilicity-hydrophobicity regulation and organelle imaging.
In this work, a versatile platform for the highly efficient preparation of graphene quantum dots (GQDs) with diverse properties was developed. First of all, an excess amount of oxidants and an additional high temperature step of the Hummers' method for the synthesis of graphene oxide (GO) was applied to obtain nanosized graphene oxide (NGO). Then, high quality GQDs (quantum yields up to 18.2%) with different photoluminescence emission wavelengths, adjustable hydrophilicity-hydrophobicity, and selective cell organelle imaging capacity can be facilely achieved through a one-pot hydrothermal reaction between the NGO and ammonia, fatty primary amines, or amino-substituted organelle targetable compounds, respectively. The superior features of the as-developed method are extremely high conversion ratio (ca. 60 wt% from graphite to the functional GQDs) and great expandability. Such a high conversion ratio is deemed to be due to effectively decreasing aggregation of the NGO (in comparison with GO) during the post-treatment process. This work provides a robust strategy for the highly efficient preparation of GQDs with diverse properties and functions, and is believed to be beneficial for boosting their applications in the future.


A butyrophilin family member critically inhibits T cell activation.
The costimulatory molecules in the B7-CD28 families are important in the regulation of T cell activation and tolerance. The butyrophilin family of proteins shares sequence and structure homology with B7 family molecules; however, the function of the butyrophilin family in the immune system has not been defined. In this study, we performed an analysis on multiple butyrophilin molecules and found that butyrophilin-like (BTNL)1 molecule functions to dampen T cell activation. BTNL1 mRNA was broadly expressed, but its protein was only found in APCs and not T cells. The putative receptor for BTNL1 was found on activated T cells and APCs. Also, recombinant BTNL1 molecule inhibited T cell proliferation by arresting cell cycle progression. The administration of neutralizing Abs against BTNL1 provoked enhanced T cell activation and exacerbated disease in autoimmune and asthma mouse models. Therefore, BTNL1 is a critical inhibitory molecule for T cell activation and immune diseases.


Developmental changes in information central to artifact representation: evidence from 'functional fluency' tasks.
Research suggests that while information about design is a central feature of older children's artifact representations it may be less important in the artifact representations of younger children. Three experiments explore the pattern of responses that 5- and 7-year-old children generate when asked to produce multiple uses for familiar (Experiments 1, 2) and novel (Experiment 3) named objects. Results showed that while older children tended to produce responses based on the known design function of the object, younger children's responses were more flexible, though still constrained by the mechanical structure of the object. Only when ignorant of a novel object's design function did older children produce more varied functions than did younger children. These results suggest that representations supporting object function undergo change across this period of development, with information about design assuming more importance later than it does earlier.


Electrochemistry provides a point-of-care approach for the marker indicative of Pseudomonas aeruginosa infection of cystic fibrosis patients.
It has recently been demonstrated that 2-aminoacetophenone (2-AA) is a chemical indicator in exhaled air/breath of Pseudomonas aeruginosa infection associated with progressive life threatening decline of lung function in cystic fibrosis sufferers [Scott-Thomas et al., BMC Pulm. Med., 2010, 10, 56]. Currently the detection of 2-AA involves laboratory based instrumentation such as mass spectrometry and a hand-held point-of-care type breath device would be ideal in providing real-time results within seconds to accelerate patient care decision-making processes. To this end, we demonstrate proof-of-concept that the chemical marker 2-AA, indicative of Pseudomonas aeruginosa infection, can be measured using electrochemical based sensing strategies. A range of commercially available electrode substrates are explored demonstrating for the first time that 2-AA is electrochemically active within aqueous based solutions providing an (electro)analytical signal. Glassy carbon, boron-doped diamond and platinum electrodes have been explored towards the electrochemical oxidation of 2-AA. Electrode fouling is observed requiring pre-treatment in the form of mechanical polishing between voltammetric scans and measurements. To alleviate this, screen-printed graphite electrodes are shown to be a more viable option for implementation into breath sensing devices and overcome the fouling problem since due to their low cost and disposable nature, a new electrode can be used for each measurement. The analytical utility of the platinum, screen-printed and boron-doped diamond electrodes were found to correspond to 6.85, 7.66 and 4.86 mM respectively. The challenges associated with the electrochemical sensing of 2-AA in breath that need to be overcome are discussed. This generic approach where electrochemical based technology is used to provide measurements for chemical markers in exhaled air/breath for medical diagnostics termed electrochemical breathprints (ec-breathprints), has the potential to be developed into a hand-held point-of-care breath diagnostic tool for identifying Pseudomonas aeruginosa infection in exhaled air/breath.


Do children with autism re-enact object movements rather than imitate demonstrator actions?
It has been suggested that autism-specific imitative deficits may be reduced or even spared in object-related activities. However, most previous research has not sufficiently distinguished object movement reenactment (learning about the ways in which object move) from imitation (learning about the topography of demonstrated actions). Twenty children with autism (CWA) and 20 typically developing children (TDC) were presented with puzzle boxes containing prizes. Test objects and experimental conditions were designed to isolate object- and action-related aspects of demonstrations. There were four types of video demonstrations: (a) a full demonstration by an adult; (b) a ghost demonstration with object movements alone; (c) mimed solutions demonstrated adjacent to the objects; and (d) random actions performed on the surface of the objects. There were no significant between-group differences in the degree to which CWA and TDC matched the full demonstrations, the actual demonstrations or in their times to first solution in any of the conditions. Although there was no clear imitative deficit in the CWA, regression analyses were conducted to explore in more detail whether diagnosis, verbal intelligence quotient (VIQ), nonverbal IQ NVIQ, age or motor coordination predicted performance. The results are discussed in relation to the use of extrinsic vs. intrinsic rewards and the interplay between motor coordination and the relative rigidity vs. pliability of objects.


Calculation and analysis of the harmonic vibrational frequencies in molecules at extreme pressure: methodology and diborane as a test case.
We present a new quantum chemical method for the calculation of the equilibrium geometry and the harmonic vibrational frequencies of molecular systems in dense medium at high pressures (of the order of GPa). The new computational method, named PCM-XP, is based on the polarizable continuum model (PCM), amply used for the study of the solvent effects at standard condition of pressure, and it is accompanied by a new method of analysis for the interpretation of the mechanisms underpinning the effects of pressure on the molecular geometries and the harmonic vibrational frequencies. The PCM-XP has been applied at the density functional theory level to diborane as a molecular system under high pressure. The computed harmonic vibrational frequencies as a function of the pressure have shown a satisfactory agreement with the corresponding experimental results, and the parallel application of the method of analysis has reveled that the effects of the pressure on the equilibrium geometry can be interpreted in terms of direct effects on the electronic charge distribution of the molecular solutes, and that the effects on the harmonic vibrational frequencies can be described in terms of two physically distinct effects of the pressure (curvature and relaxation) on the potential energy for the motion of the nuclei.


Optimization of Scat Detection Methods for a Social Ungulate, the Wild Pig, and Experimental Evaluation of Factors Affecting Detection of Scat.
Collection of scat samples is common in wildlife research, particularly for genetic capture-mark-recapture applications. Due to high degradation rates of genetic material in scat, large numbers of samples must be collected to generate robust estimates. Optimization of sampling approaches to account for taxa-specific patterns of scat deposition is, therefore, necessary to ensure sufficient sample collection. While scat collection methods have been widely studied in carnivores, research to maximize scat collection and noninvasive sampling efficiency for social ungulates is lacking. Further, environmental factors or scat morphology may influence detection of scat by observers. We contrasted performance of novel radial search protocols with existing adaptive cluster sampling protocols to quantify differences in observed amounts of wild pig (Sus scrofa) scat. We also evaluated the effects of environmental (percentage of vegetative ground cover and occurrence of rain immediately prior to sampling) and scat characteristics (fecal pellet size and number) on the detectability of scat by observers. We found that 15- and 20-m radial search protocols resulted in greater numbers of scats encountered than the previously used adaptive cluster sampling approach across habitat types, and that fecal pellet size, number of fecal pellets, percent vegetative ground cover, and recent rain events were significant predictors of scat detection. Our results suggest that use of a fixed-width radial search protocol may increase the number of scats detected for wild pigs, or other social ungulates, allowing more robust estimation of population metrics using noninvasive genetic sampling methods. Further, as fecal pellet size affected scat detection, juvenile or smaller-sized animals may be less detectable than adult or large animals, which could introduce bias into abundance estimates. Knowledge of relationships between environmental variables and scat detection may allow researchers to optimize sampling protocols to maximize utility of noninvasive sampling for wild pigs and other social ungulates.


Spherical Aberration Customization to Extend the Depth of Focus With a Clinical Adaptive Optics Visual Simulator.
To evaluate the use of the VAO adaptive optics visual simulator (Voptica SL, Murcia, Spain) for customization of spherical aberration to increase depth of focus. Through-focus visual acuity with both high- and low-contrast letters from +1.00 to -3.00 diopters (D) was measured in 17 dilated eyes with three different induced amounts of spherical aberration for a 4.5-mm pupil diameter: control (0 µm), -0.15 µm, and -0.30 µm. The defocus curves followed the same behavior with both values of contrast, but the visual acuity was 0.2 logMAR lower with low contrast. The mean values of high-contrast logMAR visual acuity at far, intermediate (67 cm), and near (40 cm) were -0.10, 0.11, and 0.37 for control, 0.04, 0.00, and 0.15 for -0.15 µm, and 0.23, 0.00, and 0.06 for -0.30 µm conditions. The 95% confidence interval ranged from ±0.14 to ±0.45 logMAR and the middle 50% of the distribution was approximately 0.2 logMAR. Negative values of spherical aberration extend the depth of focus in different ways depending on each patient. The VAO is a new instrument that allows the visual customization of spherical aberration to enhance depth of focus. [J Refract Surg. 2020;36(4):223-229.].


Synthesis of α-alkylated γ-butyrolactones with concomitant anhydride kinetic resolution using a sulfamide-based catalyst.
The Kinetic Resolution (KR) of α-alkylated enolisable disubstituted anhydrides has been shown to be possible for the first time. In the presence of an ad hoc designed novel class of bifunctional sulfamide organocatalyst, a regio-, diastereo- and enantioselective cycloaddition reaction between the enolisable anhydride and benzaldehydes provides densely functionalised γ-butyrolactones in one pot (up to 19 : 1 dr, 94% ee) with control over three contiguous stereocentres. The concomitant resolution of the starting material anhydride, provides access to a range of chiral succinate derivatives with selectivity factors up to S* = 10.5.


Religion as a cross-cultural determinant of depression in elderly Europeans: results from the EURODEP collaboration.
The protective effects of religion against late life depression may depend on the broader sociocultural environment. This paper examines whether the prevailing religious climate is related to cross-cultural differences of depression in elderly Europeans. Two approaches were employed, using data from the EURODEP collaboration. First, associations were studied between church-attendance, religious denomination and depression at the syndrome level for six EURODEP study centres (five countries, N = 8398). Secondly, ecological associations were computed by multi-level analysis between national estimates of religious climate, derived from the European Value Survey and depressive symptoms, for the pooled dataset of 13 EURODEP study centres (11 countries, N = 17,739). In the first study, depression rates were lower among regular church-attenders, most prominently among Roman Catholics. In the second study, fewer depressive symptoms were found among the female elderly in countries, generally Roman Catholic, with high rates of regular church-attendance. Higher levels of depressive symptoms were found among the male elderly in Protestant countries. Religious practice is associated with less depression in elderly Europeans, both on the individual and the national level. Religious practice, especially when it is embedded within a traditional value-orientation, may facilitate coping with adversity in later life.


Monitoring the Microevolution of Salmonella enterica in Healthy Dairy Cattle Populations at the Individual Farm Level Using Whole-Genome Sequencing.
Livestock represent a possible reservoir for facilitating the transmission of the zoonotic foodborne pathogen Salmonella enterica to humans; there is also concern that strains can acquire resistance to antimicrobials in the farm environment. Here, whole-genome sequencing (WGS) was used to characterize Salmonella strains (n = 128) isolated from healthy dairy cattle and their associated environments on 13 New York State farms to assess the diversity and microevolution of this important pathogen at the level of the individual herd. Additionally, the accuracy and concordance of multiple in silico tools are assessed, including: (i) two in silico serotyping tools, (ii) combinations of five antimicrobial resistance (AMR) determinant detection tools and one to five AMR determinant databases, and (iii) one antimicrobial minimum inhibitory concentration (MIC) prediction tool. For the isolates sequenced here, in silico serotyping methods outperformed traditional serotyping and resolved all un-typable and/or ambiguous serotype assignments. Serotypes assigned in silico showed greater congruency with the Salmonella whole-genome phylogeny than traditional serotype assignments, and in silico methods showed high concordance (99% agreement). In silico AMR determinant detection methods additionally showed a high degree of concordance, regardless of the pipeline or database used (≥98% agreement among susceptible/resistant assignments for all pipeline/database combinations). For AMR detection methods that relied exclusively on nucleotide BLAST, accuracy could be maximized by using a range of minimum nucleotide identity and coverage thresholds, with thresholds of 75% nucleotide identity and 50-60% coverage adequate for most pipeline/database combinations. In silico characterization of the microevolution and AMR dynamics of each of six serotype groups (S. Anatum, Cerro, Kentucky, Meleagridis, Newport, Typhimurium/Typhimurium variant Copenhagen) revealed that some lineages were strongly associated with individual farms, while others were distributed across multiple farms. Numerous AMR determinant acquisition and loss events were identified, including the recent acquisition of cephalosporin resistance-conferring bla CMY- and bla CTX-M-type beta-lactamases. The results presented here provide high-resolution insight into the temporal dynamics of AMR Salmonella at the scale of the individual farm and highlight both the strengths and limitations of WGS in tracking zoonotic pathogens and their associated AMR determinants at the livestock-human interface.


Reduction of the rate of protein translation in patients with myotonic dystrophy 2.
Myotonic dystrophy 2 (DM2) is an autosomal dominant, multisystem disease, which primarily affects skeletal muscle. DM2 is caused by CCTGn expansion in the intron 1 of the ZNF9 gene. Expression of the mutant CCUGn RNA changes RNA processing in patients with DM2; however, the role of ZNF9 protein in DM2 pathology has been not elucidated. ZNF9 has been shown to regulate cap-dependent and cap-independent translation. We have examined a possible role of ZNF9 in the regulation of translation in DM2 patients. We found that ZNF9 interacts with the 5' UTRs of terminal oligopyrimidine (TOP) tract mRNAs encoding human ribosomal protein, RPS17, poly(A)-binding protein 1 (PABP1), and the elongation factors, eEF1A and eEF2. The binding activity of ZNF9 toward these TOP-containing 5' UTRs is reduced in DM2 muscle. Consistent with the reduction of this activity, the levels of RPS17, PABP, eEF1A, and eEF2 proteins are also diminished in DM2 muscle. The reduction of ZNF9 RNA-binding activity in DM2 correlates with a decrease of ZNF9 protein levels in cytoplasm of DM2 muscle cells. We found that the reduction of ZNF9 is caused by expression of the mutant CCUG repeats. This decrease of proteins of translational apparatus in DM2 correlates with a reduction of a rate of protein synthesis in myoblasts from DM2 patients. We found that the ectopic expression of ZNF9 in DM2 myoblasts corrects rate of protein synthesis, suggesting that the alterations in CCUG-ZNF9-TOP mRNAs pathway are responsible for the reduction of the rate of protein translation in DM2 muscle cells.


Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease.
There are no plasma biomarkers specific for GVHD of the gastrointestinal (GI) tract, the GVHD target organ most associated with nonrelapse mortality (NRM) following hematopoietic cell transplantation (HCT). Using an unbiased, large-scale, quantitative proteomic discovery approach to identify candidate biomarkers that were increased in plasma from HCT patients with GI GVHD, 74 proteins were increased at least 2-fold; 5 were of GI origin. We validated the lead candidate, REG3α, by ELISA in samples from 1014 HCT patients from 3 transplantation centers. Plasma REG3α concentrations were 3-fold higher in patients at GI GVHD onset than in all other patients and correlated most closely with lower GI GVHD. REG3α concentrations at GVHD onset predicted response to therapy at 4 weeks, 1-year NRM, and 1-year survival (P ≤ .001). In a multivariate analysis, advanced clinical stage, severe histologic damage, and high REG3α concentrations at GVHD diagnosis independently predicted 1-year NRM, which progressively increased with higher numbers of onset risk factors present: 25% for patients with 0 risk factors to 86% with 3 risk factors present (P < .001). REG3α is a plasma biomarker of GI GVHD that can be combined with clinical stage and histologic grade to improve risk stratification of patients.


The prototype of a thermoregulatory system for measurement and control of temperature inside prosthetic socket.
Thermal related problems with prostheses are common complaints of amputee people. This article aims to introduce a thermoregulatory technique as a potential solution for those problems in prostheses wearers. A smart thermoregulatory system was designed, manufactured, and installed on a phantom model of a prosthetic socket. It captured temperature data from 16 sensors positioned at the interface between the phantom model and a silicone liner and used their average for comparison with a defined set temperature to select required heating or cooling functions for thermal equilibrium. A thin layer of Aluminum was used to transfer temperature between thermal pump and different sites around the phantom model. The feasibility of this thermoregulatory technique was confirmed by its ability to provide thermal equilibrium. Further investigations to improve the design of thermoregulatory system are necessary including temperature transfer element and power consumption based on thermal capacity and thermal inertia of the residual limb. The smart thermoregulatory system by providing thermal equilibrium between two sides of a prosthetic silicone liner can control residual limb skin temperature and sweating. Consequently, it can improve quality of life in amputee people.


Engineering the Structure and Properties of DNA-Nanoparticle Superstructures Using Polyvalent Counterions.
DNA assembly of nanoparticles is a powerful approach to control their properties and prototype new materials. However, the structure and properties of DNA-assembled nanoparticles are labile and sensitive to interactions with counterions, which vary with processing and application environment. Here we show that substituting polyamines in place of elemental counterions significantly enhanced the structural rigidity and plasmonic properties of DNA-assembled metal nanoparticles. These effects arose from the ability of polyamines to condense DNA and cross-link DNA-coated nanoparticles. We further used polyamine wrapped DNA nanostructures as structural templates to seed the growth of polymer multilayers via layer-by-layer assembly, and controlled the degree of DNA condensation, plasmon coupling efficiency, and material responsiveness to environmental stimuli by varying polyelectrolyte composition. These results highlight counterion engineering as a versatile strategy to tailor the properties of DNA-nanoparticle assemblies for various applications, and should be applicable to other classes of DNA nanostructures.


World trend of peritoneal dialysis publications.
To analyze the trend of global peritoneal dialysis (PD) publications, especially of publications in Peritoneal Dialysis International (PDI), from 1991 to 2005 according to the Institute for Scientific Information databases of the Thomson Corporation. Data were downloaded from the Web of Science, which includes the databases of Science Citation Index Expanded and Social Sciences Citation Index. The searching strategies were key-in of "peritoneal dialysis" in general search and of "SO=Peritoneal Dialysis International" in advanced search. Only articles and reviews were included in the analysis. The analysis was stratified by publication year, journal, author, country of each author's affiliation, and citation count of each paper. There were 7618 PD papers (6991 articles and 627 reviews) in 887 journals; 15.8% of them (n = 1204) were published in PDI. The annual outputs of global PD publications has been more than 500 papers since 1996, with a peak of 665 articles in 2003. In total, 18531 authors from 102 countries and areas contributed to PD publications. Authors from the USA were present in 30.6% of all papers although their global share decreased with time. A PD paper received an average of 12.7 citations. A review received more citations than an article (17.0 vs 12.3 on average), yet statistical significance was not reached (p = 0.216, Mann-Whitney U test). The number of PD research societies in the world has been growing during the past 15 years. More and more research is from countries other than the USA and the United Kingdom. Papers on PD have thus been published in many journals other than PDI, the leading journal in PD. However, the growth rate of PD publications in the world is diminishing. We present here the most likely reasons for the decrease in PD publications and propose suggestions for PDI to keep its leading role in the development of PD.


Abdominal symptoms during physical exercise and the role of gastrointestinal ischaemia: a study in 12 symptomatic athletes.
Gastrointestinal (GI) symptoms during exercise may be caused by GI ischaemia. The authors report their experience with the diagnostic protocol and management of athletes with symptomatic exercise-induced GI ischaemia. The value of prolonged exercise tonometry in the diagnostic protocol of these patients was evaluated. Patients referred for GI symptoms during physical exercise underwent a standardised diagnostic protocol, including prolonged exercise tonometry. Indicators of GI ischaemia, as measured by tonometry, were related to the presence of symptoms during the exercise test (S+ and S- tests) and exercise intensity. 12 athletes were specifically referred for GI symptoms during exercise (five males and seven females; median age 29 years (range 15-46 years)). Type of sport was cycling, long-distance running and triathlon. Median duration of symptoms was 32 months (range 7-240 months). Splanchnic artery stenosis was found in one athlete. GI ischaemia was found in six athletes during submaximal exercise. All athletes had gastric and jejunal ischaemia during maximum intensity exercise. No significant difference was found in gastric and jejunal Pco(2) or gradients between S+ and S- tests during any phase of the exercise protocol. In S+ tests, but not in S- tests, a significant correlation between lactate and gastric gradient was found. In S+ tests, the regression coefficients of gradients were higher than those in S- tests. Treatment advice aimed at limiting GI ischaemia were successful in reducing complaints in the majority of the athletes. GI ischaemia was present in all athletes during maximum intensity exercise and in 50% during submaximal exercise. Athletes with GI symptoms had higher gastric gradients per mmol/l increase in lactate, suggesting an increased susceptibility for the development of ischaemia during exercise. Treatment advice aimed at limiting GI ischaemia helped the majority of the referred athletes to reduce their complaints. Our results suggest an important role for GI ischaemia in the pathophysiology of their complaints.


Two-dimensional gel analysis of midgut proteins of Anopheles stephensi lines with different susceptibility to Plasmodium falciparum infection.
Little is known about the composition of the mosquito midgut which plays a central role in the development and subsequent transmission of malaria parasites. As a first step towards the characterization of mosquito midgut molecules involved in the transmission of malaria parasites, we analysed two-dimensional gel electrophoresis patterns of the midgut proteins of sugar-fed and blood-fed Anopheles stephensi lines of different susceptibility to P. falciparum infection. Two lines fully susceptible and one line (Pb3-9A) of reduced susceptibility were used. In the refractory line ookinetes do develop but are only inefficiently transformed into oocysts (Feldmann & Ponnudurai, 1989). The protein profiles of midguts from all sugar-fed mosquito lines were similar. However, after blood feeding, the midgut of the fully susceptible lines contained proteins not found in the midgut of line Pb3-9A. Twenty-nine such proteins were detected and are candidates for involvement in the interaction between the mosquito midgut and P. falciparum.


No known hominin species matches the expected dental morphology of the last common ancestor of Neanderthals and modern humans.
A central problem in paleoanthropology is the identity of the last common ancestor of Neanderthals and modern humans ([N-MH]LCA). Recently developed analytical techniques now allow this problem to be addressed using a probabilistic morphological framework. This study provides a quantitative reconstruction of the expected dental morphology of the [N-MH]LCA and an assessment of whether known fossil species are compatible with this ancestral position. We show that no known fossil species is a suitable candidate for being the [N-MH]LCA and that all late Early and Middle Pleistocene taxa from Europe have Neanderthal dental affinities, pointing to the existence of a European clade originated around 1 Ma. These results are incongruent with younger molecular divergence estimates and suggest at least one of the following must be true: (i) European fossils and the [N-MH]LCA selectively retained primitive dental traits; (ii) molecular estimates of the divergence between Neanderthals and modern humans are underestimated; or (iii) phenotypic divergence and speciation between both species were decoupled such that phenotypic differentiation, at least in dental morphology, predated speciation.


Novel method for DNA methylation analysis using high-performance liquid chromatography and its clinical application.
The aim of this study was to develop a new methodology that is suitable for DNA methylation diagnostics and to demonstrate its clinical applicability. We developed a new anion-exchange column for high-performance liquid chromatography (HPLC) with electrostatic and hydrophobic properties. Both cytosine and thymine, corresponding to methylated and unmethylated cytosine after bisulfite modification, respectively, are captured by electrostatic interaction and then discriminated from each other by their hydrophobic interactions. The DNA methylation levels of synthetic DNA were quantified accurately and reproducibly within 10 minutes without time-consuming pretreatment of PCR products, and the measured values were unaffected by the distribution of methylated CpG within the synthetic DNA fragments. When the DNA methylation status of the FAM150A gene, a marker of the CpG island methylator phenotype specific to clear cell renal cell carcinoma (ccRCC), was examined in 98 patients with ccRCC, bulk specimens of tumorous tissue including cancer cells showing DNA methylation of the FAM150A gene were easily identifiable by simply viewing the differentiated chromatograms, even when the cancer cell content was low. Sixteen ccRCC showing DNA methylation more frequently exhibited clinicopathological parameters reflecting tumor aggressiveness (ie, a larger diameter, higher histological grade, vascular involvement, renal vein tumor thrombi, infiltrating growth, tumor necrosis, renal pelvis invasion and higher pathological TNM stage), and had significantly lower recurrence-free and overall survival rates. These data indicate that HPLC analysis using this newly developed anion-exchange column could be a powerful tool for DNA methylation diagnostics, including prognostication of patients with cancers, in a clinical setting.


Translating advances in the molecular basis of schizophrenia into novel cognitive treatment strategies.
The presence and severity of cognitive symptoms, including working memory, executive dysfunction and attentional impairment, contributes materially to functional impairment in schizophrenia. Cognitive symptoms have proved to be resistant to both first- and second-generation antipsychotic drugs. Efforts to develop a consensus set of cognitive domains that are both disrupted in schizophrenia and are amenable to cross-species validation (e.g. the National Institute of Mental Health Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia and Research Domain Criteria initiatives) are an important step towards standardization of outcome measures that can be used in preclinical testing of new drugs. While causative genetic mutations have not been identified, new technologies have identified novel genes as well as hitherto candidate genes previously implicated in the pathophysiology of schizophrenia and/or mechanisms of antipsychotic efficacy. This review comprises a selective summary of these developments, particularly phenotypic data arising from preclinical genetic models for cognitive dysfunction in schizophrenia, with the aim of indicating potential new directions for pro-cognitive therapeutics. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc.


Identifying the presence of a disulfide linkage in peptides by the selective elimination of hydrogen disulfide from collisionally activated alkali and alkaline earth metal complexes.
We report a new method for identifying disulfide linkages in peptides using mass spectrometry. This is accomplished by collisional activation of singly charged cationic alkali and alkaline earth metal complexes, which results in the highly selective elimination of hydrogen disulfide (H2S2). Complexes of peptides possessing disulfide bonds with sodium and alkaline earth metal are generated using electrospray ionization (ESI). Isolation followed by collision induced dissociation (CID) of singly charged peptide complexes results in selective elimination of H2S2 to leave newly formed dehydroalanine residues in the peptide. Further activation of the product yields sequence information in the region previously short circuited by the disulfide bond. For example, singly charged magnesium and calcium ion bound complexes of [Lys8]-vasopressin exhibit selective elimination of H2S2 via low-energy CID. Further isolation of the product followed by CID yields major b- and z-type fragments revealing the peptide sequence in the region between the newly formed dehydroalanine residues. Numerous model peptides provide mechanistic details for the selective elimination of H2S2. The process is initiated starting with a metal stabilized enolate anion at Cys, followed by cleavage of the S-C bond. An examination of the peptic digest of insulin provides an example of the application of the selective elimination of H2S2 for the identification of peptides with disulfide linkages. The energetics and mechanisms of H2S2 elimination from model compounds are investigated using density functional theory (DFT) calculations.


Impact of vaccination on new SARS-CoV-2 infections in the United Kingdom.
The effectiveness of COVID-19 vaccination in preventing new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the general community is still unclear. Here, we used the Office for National Statistics COVID-19 Infection Survey-a large community-based survey of individuals living in randomly selected private households across the United Kingdom-to assess the effectiveness of the BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca; ChAdOx1) vaccines against any new SARS-CoV-2 PCR-positive tests, split according to self-reported symptoms, cycle threshold value (<30 versus ≥30; as a surrogate for viral load) and gene positivity pattern (compatible with B.1.1.7 or not). Using 1,945,071 real-time PCR results from nose and throat swabs taken from 383,812 participants between 1 December 2020 and 8 May 2021, we found that vaccination with the ChAdOx1 or BNT162b2 vaccines already reduced SARS-CoV-2 infections ≥21 d after the first dose (61% (95% confidence interval (CI) = 54-68%) versus 66% (95% CI = 60-71%), respectively), with greater reductions observed after a second dose (79% (95% CI = 65-88%) versus 80% (95% CI = 73-85%), respectively). The largest reductions were observed for symptomatic infections and/or infections with a higher viral burden. Overall, COVID-19 vaccination reduced the number of new SARS-CoV-2 infections, with the largest benefit received after two vaccinations and against symptomatic and high viral burden infections, and with no evidence of a difference between the BNT162b2 and ChAdOx1 vaccines.


Diagnostic Metabolomic Blood Tests for Endoluminal Gastrointestinal Cancer--A Systematic Review and Assessment of Quality.
Advances in analytics have resulted in metabolomic blood tests being developed for the detection of cancer. This systematic review aims to assess the diagnostic accuracy of blood-based metabolomic biomarkers for endoluminal gastrointestinal (GI) cancer. Using endoscopic diagnosis as a reference standard, methodologic and reporting quality was assessed using validated tools, in addition to pathway-based informatics to biologically contextualize discriminant features. Twenty-nine studies (15 colorectal, 9 esophageal, 3 gastric, and 2 mixed) with data from 10,835 participants were included. All reported significant differences in hematologic metabolites. In pooled analysis, 246 metabolites were found to be significantly different after multiplicity correction. Incremental metabolic flux with disease progression was frequently reported. Two promising candidates have been validated in independent populations (both colorectal biomarkers), and one has been approved for clinical use. Networks analysis suggested modulation of elements of up to half of Edinburgh Human Metabolic Network subdivisions, and that the poor clinical applicability of commonly modulated metabolites could be due to extensive molecular interconnectivity. Methodologic and reporting quality was assessed as moderate-to-poor. Serum metabolomics holds promise for GI cancer diagnostics; however, future efforts must adhere to consensus standardization initiatives, utilize high-resolution discovery analytics, and compare candidate biomarkers with peer nonendoscopic alternatives.


Varidnaviruses in the Human Gut: A Major Expansion of the Order Vinavirales.
Bacteriophages play key roles in the dynamics of the human microbiome. By far the most abundant components of the human gut virome are tailed bacteriophages of the realm Duplodnaviria, in particular, crAss-like phages. However, apart from duplodnaviruses, the gut virome has not been dissected in detail. Here we report a comprehensive census of a minor component of the gut virome, the tailless bacteriophages of the realm Varidnaviria. Tailless phages are primarily represented in the gut by prophages, that are mostly integrated in genomes of Alphaproteobacteria and Verrucomicrobia and belong to the order Vinavirales, which currently consists of the families Corticoviridae and Autolykiviridae. Phylogenetic analysis of the major capsid proteins (MCP) suggests that at least three new families should be established within Vinavirales to accommodate the diversity of prophages from the human gut virome. Previously, only the MCP and packaging ATPase genes were reported as conserved core genes of Vinavirales. Here we report an extended core set of 12 proteins, including MCP, packaging ATPase, and previously undetected lysis enzymes, that are shared by most of these viruses. We further demonstrate that replication system components are frequently replaced in the genomes of Vinavirales, suggestive of selective pressure for escape from yet unknown host defenses or avoidance of incompatibility with coinfecting related viruses. The results of this analysis show that, in a sharp contrast to marine viromes, varidnaviruses are a minor component of the human gut virome. Moreover, they are primarily represented by prophages, as indicated by the analysis of the flanking genes, suggesting that there are few, if any, lytic varidnavirus infections in the gut at any given time. These findings complement the existing knowledge of the human gut virome by exploring a group of viruses that has been virtually overlooked in previous work.


Investigating the biological potential of galactic cosmic ray-induced radiation-driven chemical disequilibrium in the Martian subsurface environment.
There is growing evidence suggesting the presence of aqueous environment on ancient Mars, raising the question of the possibility of life in such an environment. Subsequently, with the erosion of the Martian atmosphere resulting in drastic changes in its climate, surface water disappeared, shrinking habitable spaces on the planet, with only a limited amount of water remaining near the surface in form of brines and water-ice deposits. Life, if it ever existed, would have had to adapt to harsh modern conditions, which includes low temperatures and surface pressure, and high radiation dose. Presently, there is no evidence of any biological activity on the planet's surface, however, the subsurface environment, which is yet to be explored, is less harsh, has traces of water in form of water-ice and brines, and undergoes radiation-driven redox chemistry. I hypothesize that Galactic Cosmic Ray (GCR)-induced radiation-driven chemical disequilibrium can be used for metabolic energy by extant life, and host organisms using mechanisms seen in similar chemical and radiation environments on Earth. I propose a GCR-induced radiolytic zone, and discuss the prospects of finding such life with Rosalind Franklin rover of the ExoMars mission.


Nitrogen excretion at different stages of growth and its association with production traits in growing pigs.
The objectives of this study were to determine nitrogen loss at different stages of growth and during the entire growing period and to investigate the associations between nitrogen excretion and production traits in growing pigs. Data from 315 pigs of an F(2) population which originated from crossing Pietrain sires with a commercial dam line were used. Nitrogen retention was derived from protein retention as measured using the deuterium dilution technique during different stages of growth (60 to 90 kg, 90 to 120 kg, and 120 to 140 kg). Pigs were fed ad libitum with 2 pelleted diets containing 17% (60 to 90 kg) and 16.5% (90 to 120 and 120 to 140 kg) CP. Average daily nitrogen excretion (ADNE) within each stage of growth was calculated on the basis of the accumulated difference between average daily nitrogen intake (ADNI) and average daily nitrogen retention (ADNR). Least ADNE, nitrogen excretion per BW gain (NEWG) and total nitrogen excretion (TNE) were observed during growth from 60 to 90 kg. In contrast, the greatest ADNE, NEWG, and TNE were found during growth from 120 to 140 kg. Statistical analyses indicated that gender, housing type, the ryanodine receptor 1 (RYR1) gene, and batch influenced nitrogen excretion (P < 0.05), but the degree and direction of influences differed between growth stages. Gender differences showed that gilts excreted less nitrogen than barrows (P < 0.05), which was associated with decreased feed conversion ratio (FCR; feed:gain) and lipid:protein gain ratio. Single-housed pigs showed reduced nitrogen excretion compared with group-housed pigs (P < 0.05). In comparison to other genotypes, pigs carrying genotype NN (homozygous normal) at the RYR1 locus had the least nitrogen excretion (P < 0.05) at all stages of growth except from 60 to 90 kg. The residual correlations indicated that NEWG and TNE have large positive correlations with FCR (r = 0.99 and 0.91, respectively) and moderate negative correlations with ADG (r = -0.53 and -0.48, respectively), for the entire growing period. Improvement in FCR, increase in ADG and reduction in lipid:protein gain ratio by 1 phenotypic SD reduced TNE per pig by 709 g, 307 g, and 211 g, respectively, over the entire growing period. The results indicate that nitrogen excretion changes substantially during growth, and it can be reduced most effectively by improvement of feed efficiency and to a lesser extent through the improvement of BW gain or body composition or both.


Relationship between Urinary Level of Phytate and Valvular Calcification in an Elderly Population: A Cross-Sectional Study.
Pathological calcification generally consists of the formation of solid deposits of hydroxyapatite (calcium phosphate) in soft tissues. Supersaturation is the thermodynamic driving force for crystallization, so it is believed that higher blood levels of calcium and phosphate increase the risk of cardiovascular calcification. However several factors can promote or inhibit the natural process of pathological calcification. This cross-sectional study evaluated the relationship between physiological levels of urinary phytate and heart valve calcification in a population of elderly out subjects. A population of 188 elderly subjects (mean age: 68 years) was studied. Valve calcification was measured by echocardiography. Phytate determination was performed from a urine sample and data on blood chemistry, end-systolic volume, concomitant diseases, cardiovascular risk factors, medication usage and food were obtained. The study population was classified in three tertiles according to level of urinary phytate: low (<0.610 μM), intermediate (0.61-1.21 μM), and high (>1.21 μM). Subjects with higher levels of urinary phytate had less mitral annulus calcification and were less likely to have diabetes and hypercholesterolemia. In the multivariate analysis, age, serum phosphorous, leukocytes total count and urinary phytate excretion appeared as independent factors predictive of presence of mitral annulus calcification. There was an inverse correlation between urinary phytate content and mitral annulus calcification in our population of elderly out subjects. These results suggest that consumption of phytate-rich foods may help to prevent cardiovascular calcification evolution.