Potato virus X-based expression vectors are stabilized for long-term production of proteins and larger inserts.
Plus-strand RNA viruses such as Potato virus X (PVX) are often used as high-yielding expression vectors in plants, because they tolerate extra transgene insertion and expression without disrupting normal virus functions. However, sequence redundancy due to promoter duplication often leads to genetic instability. Although heterologous subgenomic promoter-like sequences (SGPs) have been successfully used in Tobacco mosaic virus vectors, only homologous SGP duplications have been used in PVX vectors. We stabilized PVX-based vectors by combining heterologous SGPs from related potexviruses with an N-terminal coat protein (CP) deletion. We selected two SGPs with core sequences homologous to PVX, from Bamboo mosaic virus (BaMV) and Cassava common mosaic virus, as well as a SGP with a heterologous core sequence from Foxtail mosaic virus (FoMV). We found that only the BaMV and CsCMV SGPs were utilized by the PVX replicase. However, the transgene remained unstable, due to the presence of an additional region with strong sequence similarity at the 5' end of the cp gene. The BaMV SGP combined with an N-terminal CP deletion achieved high PVX vector stability. This new expression vector is particularly useful for long-term production of proteins and for larger inserts. The improved PVX-based vectors are suitable for the systemic expression of any gene of interest in PVX host plants. The PVX-based vector can be advantageous for the overexpression of proteins, to analyze protein functions in planta or as a system for virus-induced gene silencing.


Longitudinal Within-Person Associations Between Quality of Social Relations, Structure of Social Relations, and Cognitive Functioning in Older Age.
Individuals' social connections and interpersonal experiences can both shape and be shaped by cognitive functioning. This study examines longitudinal within-person associations between quality of social relations, structure of social relations, and cognitive functioning in older age. We examined 16-year longitudinal data (3 waves) from 497 older adults (M = 66.07 years, SD = 0.83, range = 64-68 years) from the Interdisciplinary Longitudinal Study of Adult Development and Aging. Quality of social relations was measured by scales on perceived emotional support, instrumental support, and social integration. Structure of social relations was measured by self-reported number of leisure time partner types, indicating social network diversity. Cognitive functioning was assessed as a latent construct consisting of five cognitive tests (i.e., Information, Similarities, Letter Fluency, Picture Completion, Block Design). We used a random intercept cross-lagged panel model in the analysis. At the within-person level, prior quality of social relations, but not structure of social relations, was positively associated with subsequent cognitive functioning. Moreover, prior cognitive functioning was positively associated with subsequent structure of social relations, but not with quality of social relations. Quality of social relations is a protective factor of cognitive aging. Additionally, responding to prior lower cognitive functioning, social network diversity reduced, but quality of social relations did not seem to change. Overall, this study suggested that social relations and cognitive functioning mutually influence each other, but different aspects of social relations (i.e., quality, structure) might have different directional associations with cognitive functioning.


Elevated soluble ST2 and depression increased the risk of all-cause mortality and hospitalization in patients with heart failure.
This study aimed to assess the predictive effect of soluble ST2 (sST2) and depressive symptoms in patients with heart failure (HF) and to determine whether the prognosis of HF patients with preserved ejection fraction (HFpEF) differs from those with reduced ejection fraction (HFrEF). A cohort of 233 HF patients was followed for 1 year. Depressive symptoms were evaluated by the Hospital Anxiety and Depression Scale. The primary endpoint was all-cause mortality and HF-related hospitalization. For the analysis of survival, the left ventricular ejection fraction (LVEF) cut-offs for defining HFpEF were set at 50%, 45%, and 40%, respectively. With increasing LVEF, levels of sST2 were gradually decreased (45.2 ng/mL, 35.8 ng/mL, and 32.1 ng/mL in patients with LVEF ≤ 40%, 41% to 49%, and ≥ 50%, respectively, P for trend < 0.001), as well as the prevalence of depressive symptoms (35.4%, 33.3%, and 20.4%, respectively, P for trend = 0.022). After 1-year follow-up, 128 patients (54.9%) achieved the primary endpoint and 47 patients (20.2%) died. Depressive symptoms were independent risk factors of all-cause mortality and HF-related hospitalization. The combined presence of elevated sST2 (> 36.0 ng/mL) and depressive symptoms was associated with a 4.9-fold increased risk of the primary endpoint. Regardless of LVEF cut-offs, the associated risk of adverse outcomes in HFpEF was as high as in HFrEF after adjustment for significant risk factors including sST2 and N-terminal pro-brain natriuretic peptide. In conclusion, depressive symptoms provided additional prognostic information to that of sST2 in HF patients. The prognosis of HFpEF patients was similar to that of HFrEF patients.


A conserved signaling pathway: the Drosophila toll-dorsal pathway.
The Toll-Dorsal pathway in Drosophila and the interleukin-1 receptor (IL-1R)-NF-kappa B pathway in mammals are homologous signal transduction pathways that mediate several different biological responses. In Drosophila, genetic analysis of dorsal-ventral patterning of the embryo has defined the series of genes that mediate the Toll-Dorsal pathway. Binding of extracellular ligand activates the transmembrane receptor Toll, which requires the novel protein Tube to activate the cytoplasmic serine/threonine kinase Pelle. Pelle activity controls the degradation of the Cactus protein, which is present in a cytoplasmic complex with the Dorsal protein. Once Cactus is degraded in response to signal, Dorsal is free to move into the nucleus where it regulates transcription of specific target genes. The Toll, tube, pelle, cactus, and dorsal genes also appear to be involved in Drosophila immune response. Because the IL-1R-NF-kappa B pathway plays a role in vertebrate innate immunity and because plant homologues of the Toll-Dorsal pathway are important in plant disease resistance, it is likely that this pathway arose before the divergence of plants and animals as a defense against pathogens.


Outcomes of pneumatic dilation in pediatric caustic esophageal strictures: a descriptive and analytic study from a developing country.
Corrosive substance ingestion in children represents a significant public health issue due to its long-term health sequelae. Esophageal stricture, main complication of this dangerous condition, is treated by pneumatic dilation and eventually by esophageal replacement. We aimed, through this study, to report the outcomes of esophageal pneumatic dilation complicating corrosive substance ingestion in children in a developing country. This cross-sectional study was performed on the population of pediatric patients with caustic esophageal stenosis between January 2005 and December 2020. All patients underwent pneumatic balloon dilation. A logistic regression model was built to predict the probability of the occurrence of the event (success/failure) of the dilation. The ROC curve is used to evaluate the performance of the logistic regression model to discriminate between positive and negative values of the dependent variable. The success rate of pneumatic balloon dilation was 80.4%. The median duration of overall management was 11 months. The severity of caustic stricture observed during endoscopy was significantly linked to worse outcomes (p = 0.001). Multivariate analysis indicated that the severity of stenosis and the number of dilation sessions were independent risk factors for failure of dilation. ROC curve analysis showed that the area under the curve was 71.7%. A Cut-Off point value of 7 provided the best sensitivity and specificity. Pneumatic balloon dilation has been proven to be efficacious in infants with caustic esophageal stricture. Pediatric surgeons should take into account factors to promptly switch to replacement surgery and avoid unnecessary and time-consuming serial dilations.


IP6K1 is essential for chromatoid body formation and temporal regulation of Tnp2 and Prm2 expression in mouse spermatids.
Inositol hexakisphosphate kinases (IP6Ks) are enzymes that synthesise the inositol pyrophosphate 5-diphosphoinositol pentakisphosphate (5-IP7), which is known to regulate several physiological processes. Deletion of IP6K1, but not other IP6K isoforms, causes sterility in male mice. Here, we present a detailed investigation of the specific function of IP6K1 in spermatogenesis. Within the mouse testis, IP6K1 is expressed at high levels in late stage pachytene spermatocytes and in round spermatids. We found IP6K1 to be a novel component of the chromatoid body, a cytoplasmic granule found in round spermatids that is composed of RNA and RNA-binding proteins, and noted that this structure is absent in Ip6k1-/- round spermatids. Furthermore, juvenile spermatids from Ip6k1-/- mice display premature expression of the transition protein TNP2 and the protamine PRM2 due to translational derepression. The aberrant localisation of these key sperm-specific chromatin components, together with the persistence of somatic histones, results in abnormal spermatid elongation, failure to complete spermatid differentiation and azoospermia in these mice. Our study thus identifies IP6K1 as an indispensable factor in the temporal regulation of male germ cell differentiation.This article has an associated First Person interview with the first author of the paper.


Evidence for a possible extinction debt in Swiss wetland specialist plants.
Habitat loss leading to smaller patch sizes and decreasing connectivity is a major threat to global biodiversity. While some species vanish immediately after a change in habitat conditions, others show delayed extinction, that is, an extinction debt. In case of an extinction debt, the current species richness is higher than expected under present habitat conditions.We investigated wetlands of the canton of Zürich in the lowlands of Eastern Switzerland where a wetland loss of 90% over the last 150 years occurred. We related current species richness to current and past patch area and connectivity (in 1850, 1900, 1950, and 2000). We compared current with predicted species richness in wetlands with a substantial loss in patch area based on the species-area relationship of wetlands without substantial loss in patch area and studied relationships between the richness of different species groups and current and historical area and connectivity of wetland patches.We found evidence of a possible extinction debt for long-lived wetland specialist vascular plants: in wetlands, which substantially lost patch area, current species richness of long-lived specialist vascular plants was higher than would have been expected based on current patch area. Additionally and besides current wetland area, historical area also explained current species richness of these species in a substantial and significant way. No evidence for an extinction debt in bryophytes was found.The possible unpaid extinction debt in the wetlands of the canton of Zürich is an appeal to nature conservation, which has the possibility to prevent likely future extinctions of species through specific conservation measures. In particular, a further reduction in wetlands must be prevented and restoration measures must be taken to increase the number of wetlands.


Transcriptome analysis of psoriasis in a large case-control sample: RNA-seq provides insights into disease mechanisms.
To increase our understanding of psoriasis, we used high-throughput complementary DNA sequencing (RNA-seq) to assay the transcriptomes of lesional psoriatic and normal skin. We sequenced polyadenylated RNA-derived complementary DNAs from 92 psoriatic and 82 normal punch biopsies, generating an average of ∼38 million single-end 80-bp reads per sample. Comparison of 42 samples examined by both RNA-seq and microarray revealed marked differences in sensitivity, with transcripts identified only by RNA-seq having much lower expression than those also identified by microarray. RNA-seq identified many more differentially expressed transcripts enriched in immune system processes. Weighted gene coexpression network analysis (WGCNA) revealed multiple modules of coordinately expressed epidermal differentiation genes, overlapping significantly with genes regulated by the long noncoding RNA TINCR, its target gene, staufen-1 (STAU1), the p63 target gene ZNF750, and its target KLF4. Other coordinately expressed modules were enriched for lymphoid and/or myeloid signature transcripts and genes induced by IL-17 in keratinocytes. Dermally expressed genes were significantly downregulated in psoriatic biopsies, most likely because of expansion of the epidermal compartment. These results show the power of WGCNA to elucidate gene regulatory circuits in psoriasis, and emphasize the influence of tissue architecture in both differential expression and coexpression analysis.


Enzymatic Characterization of a Novel HSL Family IV Esterase EstD04 from Pseudomonas sp. D01 in Mealworm Gut Microbiota.
Pseudomonas sp. D01, capable of growing in tributyrin medium, was isolated from the gut microbiota of yellow mealworm. By using in silico analyses, we discovered a hypothesized esterase encoding gene in the D01 bacterium, and its encoded protein, EstD04, was classified as a bacterial hormone-sensitive lipase (bHSL) of the type IV lipase family. The study revealed that the recombinant EstD04-His(6x) protein exhibited esterase activity and broad substrate specificity, as it was capable of hydrolyzing p-nitrophenyl derivatives with different acyl chain lengths. By using the most favorable substrate p-nitrophenyl butyrate (C4), we defined the optimal temperature and pH value for EstD04 esterase activity as 40 °C and pH 8, respectively, with a catalytic efficiency (kcat/Km) of 6.17 × 103 mM-1 s-1 at 40 °C. EstD04 demonstrated high stability between pH 8 and 10, and thus, it might be capably used as an alkaline esterase in industrial applications. The addition of Mg2+ and NH4+, as well as DMSO, could stimulate EstD04 enzyme activity. Based on bioinformatic motif analyses and tertiary structural simulation, we determined EstD04 to be a typical bHSL protein with highly conserved motifs, including a triad catalytic center (Ser160, Glu253, and His283), two cap regions, hinge sites, and an oxyanion hole, which are important for the type IV enzyme activity. Moreover, the sequence analysis suggested that the two unique discrete cap regions of EstD04 may contribute to its alkali mesophilic nature, allowing EstD04 to exhibit extremely distinct physiological properties from its evolutionarily closest esterase.


Prediction of Complications and Prognostication in Perioperative Medicine: A Systematic Review and PROBAST Assessment of Machine Learning Tools.
The utilization of artificial intelligence and machine learning as diagnostic and predictive tools in perioperative medicine holds great promise. Indeed, many studies have been performed in recent years to explore the potential. The purpose of this systematic review is to assess the current state of machine learning in perioperative medicine, its utility in prediction of complications and prognostication, and limitations related to bias and validation. A multidisciplinary team of clinicians and engineers conducted a systematic review using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol. Multiple databases were searched, including Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, PubMed, Medline, Embase, and Web of Science. The systematic review focused on study design, type of machine learning model used, validation techniques applied, and reported model performance on prediction of complications and prognostication. This review further classified outcomes and machine learning applications using an ad hoc classification system. The Prediction model Risk Of Bias Assessment Tool (PROBAST) was used to assess risk of bias and applicability of the studies. A total of 103 studies were identified. The models reported in the literature were primarily based on single-center validations (75%), with only 13% being externally validated across multiple centers. Most of the mortality models demonstrated a limited ability to discriminate and classify effectively. The PROBAST assessment indicated a high risk of systematic errors in predicted outcomes and artificial intelligence or machine learning applications. The findings indicate that the development of this field is still in its early stages. This systematic review indicates that application of machine learning in perioperative medicine is still at an early stage. While many studies suggest potential utility, several key challenges must be first overcome before their introduction into clinical practice.


The Veterans' Administration Cooperative Urological Research Group studies of carcinoma of the prostate: a review.
The Veterans' Administration Cooperative Urological Research Group has conducted three consecutive randomized clinical trials of various treatments for all stages of prostatic carcinoma. Thus far, a total of 3774 patients have been entered into these three main studies. The first study showed that early endocrine treatment of patients with advanced prostatic cancer did not increase overall survival when compared to initial treatment with placebo alone. Diethylstilbestrol, when given in a dose of 5.0 mg/day, was associated with an increased incidence of cardiovascular deaths. In the second study, diethylstilbestrol given in a dose of 1.0 mg/day has been as effective as the 5.0-mg dose in controlling the prostatic carcinoma but has been associated with a lower incidence of cardiovascular deaths. Patients are still being entered into the third study and it is too early to report the findings in detail.


A Bootstrap Metropolis-Hastings Algorithm for Bayesian Analysis of Big Data.
Markov chain Monte Carlo (MCMC) methods have proven to be a very powerful tool for analyzing data of complex structures. However, their computer-intensive nature, which typically require a large number of iterations and a complete scan of the full dataset for each iteration, precludes their use for big data analysis. In this paper, we propose the so-called bootstrap Metropolis-Hastings (BMH) algorithm, which provides a general framework for how to tame powerful MCMC methods to be used for big data analysis; that is to replace the full data log-likelihood by a Monte Carlo average of the log-likelihoods that are calculated in parallel from multiple bootstrap samples. The BMH algorithm possesses an embarrassingly parallel structure and avoids repeated scans of the full dataset in iterations, and is thus feasible for big data problems. Compared to the popular divide-and-combine method, BMH can be generally more efficient as it can asymptotically integrate the whole data information into a single simulation run. The BMH algorithm is very flexible. Like the Metropolis-Hastings algorithm, it can serve as a basic building block for developing advanced MCMC algorithms that are feasible for big data problems. This is illustrated in the paper by the tempering BMH algorithm, which can be viewed as a combination of parallel tempering and the BMH algorithm. BMH can also be used for model selection and optimization by combining with reversible jump MCMC and simulated annealing, respectively.


Design of Probabilistic Random Forests with Applications to Anticancer Drug Sensitivity Prediction.
Random forests consisting of an ensemble of regression trees with equal weights are frequently used for design of predictive models. In this article, we consider an extension of the methodology by representing the regression trees in the form of probabilistic trees and analyzing the nature of heteroscedasticity. The probabilistic tree representation allows for analytical computation of confidence intervals (CIs), and the tree weight optimization is expected to provide stricter CIs with comparable performance in mean error. We approached the ensemble of probabilistic trees' prediction from the perspectives of a mixture distribution and as a weighted sum of correlated random variables. We applied our methodology to the drug sensitivity prediction problem on synthetic and cancer cell line encyclopedia dataset and illustrated that tree weights can be selected to reduce the average length of the CI without increase in mean error.


Content validity and psychometric evaluation of the Functional Assessment of Chronic Illness Therapy-Fatigue scale in patients with chronic lymphocytic leukemia.
Fatigue is a prominent symptom in individuals with chronic lymphocytic leukemia (CLL). This work evaluates the content validity and psychometric properties of the Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-Fatigue) in patients with CLL to determine if it is fit for purpose in CLL research. The FACIT-Fatigue yields a 13-item total score from a five-item symptom subscale and an eight-item impact subscale. To evaluate content validity, cognitive debriefing interviews were conducted with 40 patients with CLL in the first-line or relapsed or refractory setting. Psychometric properties, including structural validity, internal consistency, construct and known-groups validity, were investigated using data from a phase 3 trial in relapsed or refractory CLL (NCT02970318). Interviewed patients considered the FACIT-Fatigue items relevant to their CLL experience, understood the terminology and agreed with response options. Confirmatory factor analysis confirmed the presence of symptom and impact subscales, but also supported unidimensionality of the FACIT-Fatigue. The FACIT-Fatigue total, symptom and impact subscales demonstrated good internal consistency (Cronbach's coefficient α > 0.85 and McDonald's omega ω > 0.90), and strong correlations with relevant EORTC QLQ-C30 scales (all Spearman's r ≥ 0.5). Known-groups validity was shown by significant differences between groups defined by baseline performance status, hemoglobin level and constitutional symptoms (all p < .0001). Cluster analysis supported FACIT-Fatigue score thresholds of 30 and 34 to define a severe fatigue population. Content validity and psychometric evaluation in patients with CLL demonstrated that the FACIT-Fatigue has good psychometric properties and is fit for purpose in CLL.


Transanal endoscopic microsurgery: the first attempt in treatment of rectal amyloidoma.
Localized amyloidosis is characterized by amyloid protein deposition restricted to one organ or tissue without systemic involvement. Gastrointestinal manifestations of localized amyloidoma are unusual, which makes amyloidoma restricted to the rectum a very rare diagnosis requiring a high index of suspicion. We present a rare account for rectal amyloidoma with an unusual presentation of obstructive symptoms and its treatment using a sophisticated surgical modality, transanal endoscopic microsurgery (TEM), which resulted in complete excision of the lesion without hospitalization and complications. The successful treatment for this rectal amyloidoma using TEM emphasizes the need to broaden its application in the treatment of various rectal lesions while preserving organ function and decreasing recurrence.


Surgical navigation by autostereoscopic image overlay of integral videography.
This paper describes an autostereoscopic image overlay technique that is integrated into a surgical navigation system to superimpose a real three-dimensional (3-D) image onto the patient via a half-silvered mirror. The images are created by employing a modified version of integral videography (IV), which is an animated extension of integral photography. IV records and reproduces 3-D images using a microconvex lens array and flat display; it can display geometrically accurate 3-D autostereoscopic images and reproduce motion parallax without the need for special devices. The use of semitransparent display devices makes it appear that the 3-D image is inside the patient's body. This is the first report of applying an autostereoscopic display with an image overlay system in surgical navigation. Experiments demonstrated that the fast IV rendering technique and patient-image registration method produce an average registration accuracy of 1.13 mm. Experiments using a target in phantom agar showed that the system can guide a needle toward a target with an average error of 2.6 mm. Improvement in the quality of the IV display will make this system practical and its use will increase surgical accuracy and reduce invasiveness.


Limonoids from Aphanamixis polystachya and their antifeedant activity.
Eight new aphanamixoid-type aphanamixoids (C-J, 1-8) and six new prieurianin-type limonoids, aphanamixoids K-P (9-14), along with 10 known terpenoids were isolated from Aphanamixis polystachya, and their structures were established by spectroscopic data analysis. Among the new limonoids, 13 compounds exhibited antifeedant activity against the generalist Helicoverpa armigera, a plant-feeding insect, at various concentration levels. In particular, compounds 1, 4, and 5 showed potent activities with EC50 values of 0.017, 0.008, and 0.012 μmol/cm(2), respectively. On the basis of a preliminary structure-activity relationship analysis, some potential active sites in the aphanamixoid-type limonoid molecules are proposed.


The anti-oxidation and anti-aging effects of Ganoderma lucidum in Caenorhabditis elegans.
As a traditional herbal medicine, the clinical efficacy of Ganoderma lucidum (G. lucidum, also known as Lingzhi in China) has been proved by clinical research and a large number of animal experiments. However, its pharmacological mechanism is not clear. Here, we used the Caenorhabditis elegans as an animal model to study the anti-oxidative stress and anti-aging effects of G. lucidum water extract. Our results showed that G. lucidum effectively promoted the nematodes to resist the oxidative stress of paraquat and heavy metal Cr6+, and significantly prolonged the lifespan of the nematodes. The underlining mechanisms were further investigated by focusing on the signaling pathways that regulate the stress responses and the lifespan. We found that G. lucidum protected the nematode against the insults of paraquat and heavy metals through the diet restriction pathway and the mTOR/S6K signaling pathway, respectively. Whereas, the effect of G. lucidum on the longevity of the nematode mainly depended on the germline signaling pathway. Microarray assays were conducted to reveal the gene expression profiles. The expression levels of 2746 genes were significantly changed during the aging process, of which 34 genes were reversed in their expression by the treatment of G. lucidum in aged nematodes. These results suggest that G. lucidum regulates the biophysiological processes in the nematodes through multiple signaling pathways.


Fruit and Vegetable Knowledge and Intake within an Australian Population: The AusDiab Study.
Understanding the relationship between fruit and vegetable knowledge (FVK) and fruit and vegetable intake (FVI) is an important consideration for improved public health and successful targeting of health promotion messaging. The aim of this study was to investigate the association between FVK and FVI in Australian adults and to identify subgroups most at risk of poor knowledge. Using data from the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab), we investigated associations between FVK and FVI, as well as demographic and lifestyle factors. Baseline FVK was measured using two self-reported questions. FVI was assessed using a validated, self-reported, food frequency questionnaire in 1999/00 (baseline), 2004/05, and 2011/12. Amongst the 8966 participants assessed at baseline, 24.1% had adequate, 73.0% had insufficient, and 2.9% had poor FVK. Using linear regression, those with insufficient or poor FVK reported significantly lower FVI (grams/day) compared to those with adequate FVK: baseline (coefficient (95%CI)): -67.1 (-80.0, -54.3) and -124.0 (-142.9, -105.1), respectively, whilst, at 12 years, the differences were -42.5 (-54.6, -30.5) and -94.6 (-133.8, -55.5) grams/day, respectively (all p < 0.001). Poor FVK was more likely to be reported in males, older individuals (>65 years), socio-economically disadvantaged, smokers, and those with insufficient physical activity/sedentary behavior. We demonstrate that having adequate knowledge of FVI, defined as knowing to consume fruit and vegetables several times a day for a well-balanced diet, is strongly associated with FVI, with several demographic and lifestyle factors predicting FVK. Health promotion messages aimed at increasing FVK should target these subgroups for maximal effect.


Approximate empirical relations for nonlinear photonic crystal fibers.
Approximate empirical relations for nonlinear photonic crystal fibers (PCFs) are newly proposed. Replacing a PCF with a conventional step-index fiber, closed form expressions for the effective refractive index and the effective core area of nonlinear PCFs are derived. To define the equivalent cladding index, the effective index of the so-called fundamental space-filling mode, which is calculated using empirical relations for the effective normalized frequency, is introduced, and thus, nonlinear guided waves propagating in PCFs can be easily characterized without the need for numerical computations. The validity of the method proposed here is ensured by comparing the calculated results with those obtained by a fullvector finite-element method.


Electron microscopy of cell cultures infected with a chlamydial agent causing polyarthritis of lambs.
McCoy cell cultures infected with the agent of ovine chlamydial polyarthritis were examined with the electron microscope. The agent was seen as small dense particles (250 to 450 nm) with an eccentric nucleoid and a multilaminated cell wall, as large (800 to 1,200 nm) granular particles surrounded by two unit membranes and as intermediate particles. Replication, which occurred throughout the cytoplasm, was initiated by phagocytosis of a small dense particle and terminated by rupture of the plasma membrane. Upon entering a cell, the small dense particles developed into large granular particles which divided by binary fission. Daughter particles either repeated the division or condensed to form new small dense particles.


Optimization of reduced-dose MDCT of thoracic aorta using iterative reconstruction.
To evaluate the contribution of iterative reconstruction on image quality of reduced-dose multidetector computed tomography of the thoracic aorta. A torso phantom was scanned using two tube potentials (80 and 120 kVp) and five different tube currents (110, 75, 40, 20, and 10 mAs). All images were reconstructed with both filtered back projection (FBP) and iterative reconstruction. Aortic attenuation, image noise within the thoracic aorta, signal-to-noise ratio, and sharpness of the aortic wall were quantified in the phantom for the two reconstruction algorithms. Data were analyzed using paired t test. A value of P < 0.05 was considered significant. The aortic attenuation was similar for FBP and iterative reconstruction (P > 0.05). Image noise level was lower (P < 0.0001), and image sharpness was higher (P = 0.046) with iterative reconstruction. Signal-to-noise ratios were higher with iterative reconstruction compared with those with FBP (P < 0.0001). Signal-to-noise ratio at 80 kVp with iterative reconstruction (9.8 ± 4.4) was similar to the signal-to-noise ratio at 120 kVp with FBP (8.4 ± 3.3) (P = 0.196). Less image noise and higher image sharpness may be achieved with iterative reconstruction in reduced-dose multidetector computed tomography of the thoracic aorta.


Tulbaghia alliacea phytotherapy: a potential anti-infective remedy for candidiasis.
The reproductive health of individuals is severely compromised by HIV infection, with candidiasis being the most prevalent oral complication in patients. Although not usually associated with severe morbidity, oropharyngeal candidiasis can be clinically significant, as it can interfere with the administration of medications and adequate nutritional intake, and may spread to the esophagus. Azole antifungal agents are commonly prescribed for the treatment and prophylaxis of candidal infections, however, the emergence of drug resistant strains and dose limiting toxic effects has complicated the treatment of candidiasis. Consequently, safe and effective and affordable medicine is required to combat this fungus. Commercial garlic (Allium sativum) has been used since time immemorial as a natural antibiotic, however, very little is known about the antifungal properties of two indigenous South African species of garlic, namely Tulbaghia alliacea and Tulbaghia violacea, used as folk medicines for a variety of infections. This study compares the in vitro anticandidal activity of Tulbaghia alliacea, Tulbaghia violacea and Allium sativum extracts. It was found that the greatest concentrations of inhibitory components were extracted by chloroform or water. The IC50 concentrations of Tulbaghia alliacea were 0.007-0.038% (w/v). Assays using S. cerevisiae revealed that the T. alliacea extract was fungicidal, with a killing half-life of approximately 2 h. This inhibitory effect of the T. alliacea extracts was observed via TLC, and may be due to an active compound called marasmicin, that was identified using NMR. This investigation confirms that extracts of T. alliacea exhibit anti-infective activity against candida species in vitro.


Potential cost-effectiveness of therapeutic drug monitoring in patients with resistant hypertension.
Nonadherence to drug therapy poses a significant problem in the treatment of patients with presumed resistant hypertension. It has been shown that therapeutic drug monitoring (TDM) is a useful tool for detecting nonadherence and identifying barriers to treatment adherence, leading to effective blood pressure (BP) control. However, the cost-effectiveness of TDM in the management of resistant hypertension has not been investigated. A Markov model was used to evaluate life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios in resistant hypertension patients receiving either TDM optimized therapy or standard best medical therapy. The model ran from the age of 30 to 100 years or death, using a cycle length of 1 year. Efficacy of TDM was modeled by reducing risk of hypertension-related morbidity and mortality. Cost analyses were performed from a payer's perspective. Deterministic and probabilistic sensitivity analyses were conducted. In the age group of 60-year olds, TDM gained 1.07 QALYs in men and 0.97 QALYs in women at additional costs of €3854 and €3922, respectively. Given a willingness-to-pay threshold of €35,000 per QALY gained, the probability of TDM being cost-effective was 95% or more in all age groups from 30 to 90 years. Results were influenced mostly by the frequency of TDM testing, the rate of nonresponders to TDM, and the magnitude of effect of TDM on BP. Therapeutic drug monitoring presents a potential cost-effective healthcare intervention in patients diagnosed with resistant hypertension. Importantly, this finding is valid for a wide range of patients, independent of sex and age.


Short Communication: The effects of physical feed properties on gastric emptying in pigs measured with the 13C breath test.
The performance of pigs is affected by the rate of nutrient absorption in the gastrointestinal tract, which depends in turn strongly on the rate of stomach emptying. The 13C breath test provides a non-invasive diagnostic tool to measure gastric emptying patterns. Despite the wide acceptance of this method in human intervention studies, it has not found its way to the domain of animal sciences. In this study, we used the breath test to measure gastric emptying in young growing pigs using [1-13C] octanoic acid to trace digesta solids and [1-13C] glycine to study liquids. Pigs were fed a starch-rich diet, varying in starch source (isolated starch from barley, maize or high-amylose maize) or form (isolated barley starch, ground barley or extruded barley), after which 13CO2 enrichment was frequently measured during 11 h. Outliers in 13CO2 enrichment in the response curve of each pig were identified with a Cook's distance outlier test in combination with a leave-one-out analysis. Effects of experimental treatments on breath test parameters were tested using a GLM. In general, pigs were easy to train and the tailor-made mask allowed effortless sampling. Gastric emptying of all pigs followed a biphasic pattern, with a higher 13C recovery during the first peak. The first peak in gastric emptying of solids reached its maximum enrichment within 2 h after feeding in all cases. For digesta liquids, this peak was reached earlier for pigs fed ground barley (2.2 h after feeding), compared to pigs fed diets containing isolated starch (2.8 h after feeding). The second peak in gastric emptying of solids was reached later for pigs fed ground barley (5.9 h after feeding), compared with pigs fed extruded barley (4.5 h after feeding) and pigs fed diets containing isolated barley starch (4.8 h after feeding). In conclusion, the 13C breath test is a convenient, non-invasive tool to gain more insights into the gastric emptying pattern of pigs.


The role of the novel adipocyte-derived protein adiponectin in human disease: an update.
Adiponectin is a collagen-like protein expressed in adipose tissue. Low serum adiponectin is associated with insulin resistance, atherogenic hyperlipidemia and arterial hypertension. High serum adiponectin predicted a reduced risk of myocardial infarction. Other surveys have shown that high levels of serum adiponectin were a predictor of future cardiovascular disease and mortality. These paradoxical findings might be explained through the concept of the reversal epidemiology in the adiponectin physiology. According to this hypothesis, this protein would behave as an insulin sensitizing and cardioprotective factor in the health state and as a wasting marker in the advanced states of disease.


Rhodium-catalyzed Heck-type reaction of arylboronic acids with alpha,beta-unsaturated esters: tuning beta-hydrogen elimination vs. hydrolysis of alkylrhodium species.
The elusive rhodium-catalyzed Heck-type coupling of arylboronic acids with alpha,beta-unsaturated esters is effected using rhodium chloride as catalyst, indicating the hydrolysis of Rh-C bond could be finely tuned by the steric environment around rhodium.


8(th) Annual European Antibody Congress 2012: November 27-28, 2012, Geneva, Switzerland.
The 8th European Antibody Congress (EAC), organized by Terrapin Ltd., was again held in Geneva, Switzerland, following on the tradition established with the 4th EAC. The new agenda format for 2012 included three parallel tracks on: (1) naked antibodies; (2) antibody drug conjugates (ADCs); and (3) bispecific antibodies and alternative scaffolds. The meeting started and closed with three plenary lectures to give common background and to share the final panel discussion and conclusions. The two day event included case studies and networking for nearly 250 delegates who learned of the latest advances and trends in the global development of antibody-based therapeutics. The monoclonal antibody track was focused on understanding the structure-function relationships, optimization of antibody design and developability, and processes that allow better therapeutic candidates to move through the clinic. Discussions on novel target identification and validation were also included. The ADC track was dedicated to evaluation of the ongoing success of the established ADC formats alongside the rise of the next generation drug-conjugates. The bispecific and alternative scaffold track was focused on taking stock of the multitude of bispecific formats being investigated and gaining insight into recent innovations and advancements. Mechanistic understanding, progression into the clinic and the exploration of multispecifics, redirected T cell killing and alternative scaffolds were extensively discussed. In total, nearly 50 speakers provided updates of programs related to antibody research and development on-going in the academic, government and commercial sectors.


Targeting of adenoviral vectors through a bispecific single-chain antibody.
Recombinant adenoviral vectors are attractive in the context of cancer gene therapy because they are capable of delivering genes to a wide variety of tissues. The utility of adenoviruses is limited by their lack of specificity and by the absence of the receptor(s) for these viruses on many tumor cells. Redirecting adenoviral vectors to tissue- or tumor-specific targets can be achieved by using bispecific conjugates produced by chemical linkage of an anti-adenovirus antibody (Ab) and a ligand or Ab directed toward a specific target. To avoid the limitations of chemical conjugates, molecular conjugates of anti-fiber knob and ligand have been proposed. We present here a novel strategy that allows the production of recombinant bispecific single-chain Abs directed at cell surface molecules. A construct was made that encodes a neutralizing anti-adenovirus fiber single-chain Fv (scFv) Ab (S11) fused to a scFv Ab (425) directed against the epidermal growth factor receptor. The fusion protein markedly enhanced the infection efficiency of adenoviral vectors in epidermal growth factor receptor-expressing cell lines. The bispecific scFv could be purified and concentrated after binding of its 6His tag to a nickel column without significant loss of activity. This approach should permit the production of high quantities of active bispecific scFv for in vivo use. The universal design of the construct allows rapid screening for relevant specific scFv directed at cell surface antigens that can be incorporated into adenoviral targeting strategies.


Fringe formation in two-wavelength contour holography.
This paper presents a description of fringe formation in two-wavelength contour holography. Approximations are introduced primarily by restricting the recording wavelength difference with the aid of a tunable dye laser and by observing the contour fringes through a controlled viewing system aperture. Several holographic recording and readout arrangements are presented for which explicit and conveniently interpretable contour fringe formulations are derived. Finally, the results from a set of experiments performed with each of the arrangements are offered as experimental evidence supporting the analysis.


Pericardial superfusion to measure cardiac interstitial adenosine concentration.
The steady-state concentration of adenosine in pericardial superfusates, [Ado]SS, may estimate the concentration in the cardiac interstitium. As reaching a steady state may sometimes require many minutes, the concentration at an earlier time is often used as an index of [Ado]SS. The latter assumes that the rate of approach to [Ado]SS is uniform and insensitive to perturbations of cardiac oxygen usage (MVO2). In 11 open-chest dogs superfusate adenosine rose at a rate (+/- SD) of 0.53 +/- 0.99/min to an [Ado]SS of 68 +/- 32. The mean rate of equilibration has a very large coefficient of variation, indicating substantial dog-to-dog variation. In five dogs the rate of equilibration during the second of successive superfusions was significantly lower than the first. Raising MVO2 by cardiac pacing or isoproterenol infusion changed neither the rate of equilibration nor [Ado]SS. Aortic constriction or propranolol slowed equilibration but had no effect on [Ado]SS. Thus superfusate adenosine concentration early in the course of equilibration seems an unreliable index of [Ado]SS. That interventions that change MVO2 do not change [Ado]SS from control means either that [Ado]SS fails to reflect the concentration in the vicinity of the coronary resistance vessels or, alternatively, that adenosine does not regulate coronary blood flow.


A kinetic Monte Carlo approach to study fluid transport in pore networks.
The mechanism of fluid migration in porous networks continues to attract great interest. Darcy's law (phenomenological continuum theory), which is often used to describe macroscopically fluid flow through a porous material, is thought to fail in nano-channels. Transport through heterogeneous and anisotropic systems, characterized by a broad distribution of pores, occurs via a contribution of different transport mechanisms, all of which need to be accounted for. The situation is likely more complicated when immiscible fluid mixtures are present. To generalize the study of fluid transport through a porous network, we developed a stochastic kinetic Monte Carlo (KMC) model. In our lattice model, the pore network is represented as a set of connected finite volumes (voxels), and transport is simulated as a random walk of molecules, which "hop" from voxel to voxel. We simulated fluid transport along an effectively 1D pore and we compared the results to those expected by solving analytically the diffusion equation. The KMC model was then implemented to quantify the transport of methane through hydrated micropores, in which case atomistic molecular dynamic simulation results were reproduced. The model was then used to study flow through pore networks, where it was able to quantify the effect of the pore length and the effect of the network's connectivity. The results are consistent with experiments but also provide additional physical insights. Extension of the model will be useful to better understand fluid transport in shale rocks.


Joint sparse and low rank recovery algorithm for compressive hyperspectral imaging.
Compressive spectral imaging techniques encode and disperse a hyperspectral image (HSI) to sense its spatial and spectral information with few bidimensional (2D) multiplexed projections. Recovering the original HSI from the 2D projections is carried by traditional compressive sensing-based techniques that exploit the sparsity property of natural HSI as they are represented in a proper orthonormal basis. Nevertheless, HSIs also exhibit a low rank property inasmuch only a few numbers of spectral signatures are present in the images. Specifically, when an HSI is rearranged as a matrix whose columns represent vectorized 2D spatial images in a different wavelength, this matrix is said to be low rank. Therefore, this paper proposes an HSI recovering algorithm from compressed measurements involving a joint sparse and low rank optimization problem, which seeks to jointly minimize the ℓ2-, ℓ1-, and ℓ*-norm, leading the solution to fit the given projections, and be simultaneously sparse and low rank. Several simulations, along different data sets and optical sensing architectures, show that when the low rank property is included in the inverse problem formulation, the reconstruction quality increases up to four (dB) in terms of peak signal to noise ratio.


Platelet-rich plasma injections in the treatment of chronic rotator cuff tendinopathy: a randomized controlled trial with 1-year follow-up.
Rotator cuff tendinopathy (RCT) is a significant source of disability and loss of work. Platelet-rich plasma (PRP) has been suggested to be beneficial in the treatment of RCT. To investigate the effect of PRP injections on pain and shoulder functions in patients with chronic RCT. Randomized controlled trial; Level of evidence, 1. A total of 40 patients, 18 to 70 years of age, with (1) a history of shoulder pain for >3 months during overhead-throwing activities, (2) MRI findings of RCT or partial tendon ruptures, and (3) a minimum 50% reduction in shoulder pain with subacromial injections of an anesthetic were included in this placebo-controlled, double-blind randomized clinical trial. Patients were randomized into a PRP group (n = 20) or placebo group (n = 20). Patients received an ultrasound-guided injection into the subacromial space that contained either 5 mL of PRP prepared from autologous venous blood or 5 mL of saline solution. All patients underwent a 6-week standard exercise program. Outcome measures (Western Ontario Rotator Cuff Index [WORC], Shoulder Pain and Disability Index [SPADI], 100-mm visual analog scale [VAS] of shoulder pain with the Neer test, and shoulder range of motion) were assessed at baseline and at 3, 6, 12, and 24 weeks and 1 year after injection. Comparison of the patients revealed no significant difference between the groups in WORC, SPADI, and VAS scores at 1-year follow-up (P = .174, P = .314, and P = .904, respectively). Similar results were found at other assessment points. Within each group, the WORC, SPADI, and VAS scores showed significant improvements compared with baseline at all time points (P < .001). In the range of motion measures, there were no significant group × time interactions. At 1-year follow-up, a PRP injection was found to be no more effective in improving quality of life, pain, disability, and shoulder range of motion than placebo in patients with chronic RCT who were treated with an exercise program.


Antimicrobial action of copper is amplified via inhibition of heme biosynthesis.
Copper (Cu) is a potent antimicrobial agent. Its use as a disinfectant goes back to antiquity, but this metal ion has recently emerged to have a physiological role in the host innate immune response. Recent studies have identified iron-sulfur containing proteins as key targets for inhibition by Cu. However, the way in these effects at the molecular level translate into a global effect on cell physiology is not fully understood. Here, we provide a new insight into the way in which Cu poisons bacteria. Using a copA mutant of the obligate human pathogen Neisseria gonorrhoeae that lacks a Cu efflux pump, we showed that Cu overloading led to an increased sensitivity to hydrogen peroxide. However, instead of promoting disproportionation of H2O2 via Fenton chemistry, Cu treatment led to an increased lifetime of H2O2 in cultures as a result of a marked decrease in catalase activity. We showed that this observation correlated with a loss of intracellular heme. We further established that Cu inhibited the pathway for heme biosynthesis. We proposed that this impaired ability to produce heme during Cu stress would lead to the failure to activate hemoproteins that participate in key processes, such as the detoxification of various reactive oxygen and nitrogen species, and aerobic respiration. The impact would be a global disruption of cellular biochemistry and an amplified Cu toxicity.


The association between fetal nasal bone hypoplasia and aneuploidy.
To determine the association between fetal nasal bone hypoplasia and aneuploidy in women undergoing prenatal diagnosis. A prospective cohort study involving women undergoing chorionic villus sampling and amniocentesis for an increased risk of aneuploidy. Fetal biometric and nasal bone measurements were obtained at the time of prenatal diagnosis and compared with karyotypes. Nasal bone hypoplasia was defined as nasal bone less than 2.5th percentile for the gestational age. A total of 632 fetuses were evaluated. Twenty-nine (4.6%) had an aneuploidy (18 trisomy 21, 5 trisomy 18, 1 Turner's syndrome, one Marker chromosome 1, 2 sex chromosome anomalies, and 2 triploidy). Nasal bone measurements were documented in 29 aneuploid fetuses. The nasal bone was either absent or hypoplastic in 12 of 29 (41%) fetuses with aneuploidy and in 8 of 18 (44%) with trisomy 21. By using receiver operating characteristics curves, the optimal threshold of nasal bone hypoplasia associated with fetal aneuploidy was a biparietal diameter/nasal bone ratio of 11 or greater. The sensitivity, specificity, and positive and negative predictive values for the detection of fetal aneuploidy were 50%, 93%, 24%, and 98%, respectively. Absent or hypoplastic nasal bone is a marker for fetal aneuploidy in a high-risk population. However, this marker needs to be evaluated by larger prospective studies in low-risk populations before adoption for clinical use.


Association between total hypercalcaemia and iliosacral lymph node metastasis in dogs diagnosed with anal sac adenocarcinoma using abdominal ultrasonography.
Anal sac adenocarcinoma (ASACA) in dogs is a malignant perianal tumour that often metastasizes to the iliosacral lymph nodes. Additionally, this tumour can be associated with hypercalcemia of malignancy. To date, no study has looked at the association between increased blood calcium levels and suspected or confirmed lymph node metastasis as a primary objective. The objective of this study was to determine if increased total serum calcium level is associated with iliosacral lymph node metastasis in dogs diagnosed with ASACA. Medical records of a single referral hospital were searched to identify dogs examined between 2011 and 2021 that had a diagnosis of ASACA via cytology or histopathology. Only dogs that had serum total calcium recorded and abdominal ultrasound were included in the study. All images were reviewed by a board-certified radiologist blinded to any patient identifiers. Of the 58 dogs, 33% (19/58) had total hypercalcaemia, and of these, 68% had confirmed or suspected iliosacral lymph node metastasis. Total hypercalcaemia was significantly associated with confirmed or suspected iliosacral lymph node metastasis (p < 0.01). However, 46% (11/24) of dogs with confirmed or suspected iliosacral lymph node metastasis were normocalcaemic. Based on these results, it is suggested that while the presence of total hypercalcaemia may increase the likelihood of concurrent lymph node metastasis, total hypercalcaemia alone cannot be used as a screening tool for lymph node metastasis. Dogs diagnosed with ASACA should undergo full staging regardless of total serum calcium values.


Electronic Medical Records, Medical Students, and Ambulatory Family Physicians: A Multi-Institution Study.
Medical students commonly encounter electronic medical records (EMRs) in their ambulatory family medicine clerkships, but how students interact with this technology varies tremendously and presents challenges to students and preceptors. Little research to date has evaluated the impact of EMRs on medical student education in the ambulatory setting; this three-institution study aimed to identify behaviors of ambulatory family medicine preceptors as they relate to EMRs and medical students. In 2015, the authors sent e-mails to ambulatory preceptors who in the preceding year had hosted medical students during family medicine clerkships, inviting them to participate in the survey, which asked questions about each preceptor's methods of using the EMR with medical students. Of 801 ambulatory preceptors, 265 (33%) responded. The vast majority of respondents used an EMR and provided students with access to it in some way, but only 62.2% (147/236) allowed students to write electronic notes. Of those who allowed students electronic access, one-third did so by logging students in under their own (the preceptor's) credentials, either by telling the students their log-in information (22/202; 10.9%) or by logging in the student without revealing their passwords (43/202; 21.3%). Ambulatory medical student training in the use of EMRs not only varies but also requires many preceptors to break rules for students to learn important documentation skills. Without changes to the policies surrounding student access to and use of EMRs, future physicians will enter residency without the training they need to appropriately document patient care.


Antithrombotic drugs: part II.
The defibrinating agent ancrod has had limited clinical trial, but appears to give no advantages over heparin. Intravenous infusion of dextran, a glucose polymer, has been shown to have an antithrombotic effect in many experimental models of thrombosis. However, the evidence that dextran is a clinically valuable antithrombotic drug is conflicting. A number of controlled randomized studies have shown that dextran can prevent postoperative venous thromboembolism when a large volume of dextran 40 or 70 was infused rapidly during and after surgery. However, blood volume expansion during dextran treatment prohibits its use in patients with reduced cardiac reserve, and infrequent though sometimes severe, allergic reactions have been reported. Evidence that dextran is of value for the treatment of venous or arterial thromboembolism comes from uncontrolled studies and is not convincing. Many compounds have been shown to inhibit platelet function in vitro but only five of these drugs have been extensively evaluated as prophylactic or therapeutic antithrombotic agents in man. These are aspirin, sulphinpyrazone, dipyridamole, hydroxychloroquine and clofibrate. They have been evaluated mainly in patients with cerebral vascular disorders, coronary artery disease, peripheral artery ischaemia, venous thromboembolism, prosthetic heart valves, and in patients with arteriovenous shunts. The evaluation of the clinical effect of the platelet function suppressing drugs is in its early stages, but they appear to differ from each other in the spectrum of their clinical effectiveness, and they may be more effective in arterial than in venous thromboembolic disorders. Their role in the management of cerebral vascular disease and coronary artery disease is still uncertain, and should be clarified by the results of a number of multi-centre, prospective, randomized studies which are currently in progress. Three types of thrombolytic drugs have been evaluated clinically; the plasminogen activators streptokinase and urokinase, proteolytic enzymes such as plasmin, and agents which increase the level of endogenous plasminogen activator (e.g. anabolic steroids). Of these, the plasminogen activators now have a definite place in clinical practice. The plasminogen activators accelerate the lysis of recent venous thrombi and pulmonary emboli, and of arterial thrombi or emboli. Thrombolytic therapy with these agents should be considered particularly in patients with recent major pulmonary embolism, as lysis of recent emboli is rapid and substantial. It should also be considered in patients with recent extensive venous thrombosis, because total lysis of venous thrombi has been reported to result in long-term preservation of valve function, and is likely to prevent postphlebitic syndrome, though this has not been proven. However, plasminogen activator therapy carries a higher risk of bleeding than heparin treatment...


Chronic hypoxia impairs murine hippocampal development and depletes the postnatal progenitor pool by attenuating mammalian target of rapamycin signaling.
Chronic hypoxia (CH) is a major risk factor for impaired cognitive function in various disease states, particularly in the context of cyanotic congenital heart disease. Although most brain development occurs prenatally, the dentate gyrus (DG) of the hippocampus harbors progenitor stem cells that contribute to its ongoing development postnatally. It is unclear how exposure to CH might affect postnatal hippocampal development, so we used a transgenic mouse that expresses enhanced green fluorescent protein (eGFP) within this progenitor population to determine the effect of CH on the DG. We find that exposure to 10% oxygen from postnatal d 3 to 28 results in a smaller DG with long-term impairment of hippocampal neurogenesis. Because the mammalian target of rapamycin (mTOR) pathway is a well-known regulator of cell proliferation and growth and is sensitive to hypoxia, we investigated its activation on exposure to CH and find it to be attenuated specifically in neural progenitor cells. Systemic inhibition of the mTOR pathway using rapamycin also caused impairment of hippocampal neurogenesis that mimics exposure to CH. Our findings demonstrate that CH results in long-term impairment of hippocampal neurogenesis and is mediated, in part, by attenuation of the mTOR pathway.


Regulation of the spontaneous augmentation of Na(V)1.9 in mouse dorsal root ganglion neurons: effect of PKA and PKC pathways.
Sensory neurons in the dorsal root ganglion express two kinds of tetrodotoxin resistant (TTX-R) isoforms of voltage-gated sodium channels, Na(V)1.8 and Na(V)1.9. These isoforms play key roles in the pathophysiology of chronic pain. Of special interest is Na(V)1.9: our previous studies revealed a unique property of the Na(V)1.9 current, i.e., the Na(V)1.9 current shows a gradual and notable up-regulation of the peak amplitude during recording ("spontaneous augmentation of Na(V)1.9"). However, the mechanism underlying the spontaneous augmentation of Na(V)1.9 is still unclear. In this study, we examined the effects of protein kinases A and C (PKA and PKC), on the spontaneous augmentation of Na(V)1.9. The spontaneous augmentation of the Na(V)1.9 current was significantly suppressed by activation of PKA, whereas activation of PKA did not affect the voltage dependence of inactivation for the Na(V)1.9 current. On the contrary, the finding that activation of PKC can affect the voltage dependence of inactivation for Na(V)1.9 in the perforated patch recordings, where the augmentation does not occur, suggests that the effects of PMA are independent of the augmentation process. These results indicate that the spontaneous augmentation of Na(V)1.9 was regulated directly by PKA, and indirectly by PKC.


The effect of providing patient-specific electronically monitored antipsychotic medication adherence results on the treatment planning of prescribers of outpatients with schizophrenia.
Adherence to antipsychotic medication was assessed monthly over a 6-month study period using patient-specific electronic monitoring (EM) of medication bottle opening in 23 outpatients with schizophrenia or schizoaffective disorder. Patient-specific EM adherence results were then shared with the seven participating prescribers, who were surveyed concerning the treatment changes, if any, that they would recommend based on the EM adherence results. Prescribers indicated that they would recommend adherence-related treatment plan changes in 61% of patients, all of whom were ≤80% adherent. The strength of this effect was significantly stronger for psychosocial intervention treatment plan change recommendations than for medication treatment plan change recommendations. Of the psychosocial intervention recommendations, an increase in case management intensity was most often recommended. Of the medication treatment plan recommendations, initiation of a long-acting injectable medication and an increase in dosage of current oral antipsychotic medication were each recommended in only one case. Prescriber recommendations of adherence interventions in this study were not necessarily consistent with major guideline recommendations. Findings suggest the need for further study and dissemination of findings regarding evidence-based adherence assessment and interventions.


Tackling TB in migrants arriving at Europe's southern border.
Over a quarter of the individuals diagnosed with tuberculosis [TB] in the European Union region are born outside of the area and the proportion has been increasing steadily. Italy is a low TB incidence country with over 50% of TB cases in the foreign-born population primarily due to the high numbers of migrants entering the country via land or sea. As a case study to evaluate the value of screening in newly arrived migrants, the EDETECT-TB project in Italy implemented and evaluated active TB screening in the migrant population at first reception centres to ensure early diagnosis to avoid further spread. Based on a cost-effectiveness analysis from a program provider perspective, a decision tree model allowed the assessment of the value for money of case finding by estimating the cost per case of active TB detected compared with the status quo of no screening. The analysis confirmed that early case detection is a cost-effective intervention in areas with migrants arriving from high TB risk settings. Targeted post-arrival early screening of high TB risk vulnerable new entrants to Italy has a potential role in reducing the spread of TB among migrants.


Management of bilateral congenital lacrimal punctal and canalicular atresia and congenital fistula of the lacrimal sac.
An 8-year-old girl presented with complaints of bilateral epiphora since birth. The patient had congenital punctal and canalicular atresia combined with congenital fistula. She was treated successfully with surgery. A review of the literature indicated very few reports of surgical treatment of such cases.


Pancoast tumors of the lung.
Pancoast or superior pulmonary sulcus tumors are uncommon primary bronchogenic carcinomas that produce a characteristic clinical syndrome of upper extremity pain and Horner's syndrome. Treatment of patients with this malignancy has traditionally involved irradiation alone or preoperative irradiation followed by resection. Recent advances in the management of Pancoast tumors include the importance of mediastinoscopy in staging the tumor before treatment begins. A complete resection should be accomplished including a lobectomy whenever possible. The current treatment protocol involves induction chemoradiotherapy followed by surgery.


In vivo measurement of ethanol metabolism in the rat liver using magnetic resonance spectroscopy of hyperpolarized [1-13C]pyruvate.
[1-(13)C]pyruvate is a readily polarizable substrate that has been the subject of numerous magnetic resonance spectroscopy (MRS) studies of in vivo metabolism. In this work (13)C-MRS of hyperpolarized [1-(13)C]pyruvate was used to interrogate a metabolic pathway involved in neither aerobic nor anaerobic metabolism. In particular, ethanol consumption leads to altered liver metabolism, which when excessive is associated with adverse medical conditions including fatty liver disease, hepatitis, cirrhosis, and cancer. Here we present a method for noninvasively monitoring this important process in vivo. Following the bolus injection of hyperpolarized [1-(13)C]pyruvate, we demonstrate a significantly increased rat liver lactate production rate with the coadministration of ethanol (P = 0.0016 unpaired t-test). The affect is attributable to increased liver nicotinamide adenine dinucleotide (NADH) associated with ethanol metabolism in combination with NADH's role as a coenzyme in pyruvate-to-lactate conversion. Beyond studies of liver metabolism, this novel in vivo assay of changes in NADH levels makes hyperpolarized [1-(13)C]pyruvate a potentially viable substrate for studying the multiple in vivo metabolic pathways that use NADH (or NAD(+)) as a coenzyme, thus broadening the range of applications that have been discussed in the literature to date.


Impact of the pre-transplant histological score on 3-year graft outcomes of kidneys from marginal donors: a single-centre study.
The reliability of kidney biopsy as the sole means for assessing kidneys from extended-criteria donors (ECDs) to be allocated to single or dual transplantation is still a matter of debate. We compared retrospectively 3 years graft survival and renal function in 44 recipients of a single kidney graft from a marginal donor with good renal function and a Karpinski histological score of ≤ 3 and 56 recipients of a single transplant with a Karpinski score of 4 or 5. The donors' and recipients' characteristics were compared by means of Wilcoxon's rank-sum test and Fisher's exact test, and survival was analysed using the log-rank test and Cox regression survival analysis. The donors with the worse histological scores were slightly younger (68.0 ± 4.74 versus 71.3 ± 4.6 years, P < 0.01) and had a higher glomerular filtration rate (85.8 ± 28.2 versus 76.3 ± 26.53 mL/min, P = 0.013), but there was no difference in serum creatinine levels (0.83 ± 0.24 versus 0.85 ± 0.30 mg/dL, P = 0.381). Three years after transplantation, there was no difference between the two groups in terms of recipient serum creatinine levels (1.94 ± 0.69 versus 1.74 ± 0.49 mg/dL, P = 0.134), estimated glomerular filtration rate (eGFR, 45.6 ± 21.1 versus 51.7 ± 22.0 mL/min, P = 0.331) or the rates of graft loss (27.3 versus 35.7%, P = 0.47), delayed graft function or acute rejection. In our experience, provided the donor has a normal renal function, a difference in the pre-transplant histological score of kidneys from marginal cadaveric donors do not have a significant influence on the outcome 3 years after transplantation. Our findings might represent a basis for designing a randomized controlled trial of using a higher histological score threshold for the DKT allocation of grafts from ECDs with a normal renal function.


Early lung transplantation success utilizing controlled donation after cardiac death donors.
Donation-after cardiac death (DCD) donor organs have potential to significantly alleviate the shortage of transplantable lungs. However, only limited data so far describes DCD lung transplantation (LTx) techniques and results. This study aims to describe the Alfred Hospital's early and intermediate outcomes following DCD donor LTx. Following careful experimentation and consultation DCD guidelines were created to utilize Maastricht category III lung donors from either the ICU or operating room(OR), with a warm ischemic time(WIT) of <60 min. Between May 2006 and December 2007, 22 referred DCD donors led to 11 attempted retrievals after withdrawal, resulting in 8 actual bilateral LTx (2 donors did not arrest in prescribed period and 1 donor had nonacceptable lungs). ICU WIT = 38.4 min (range 20-54, OR WIT = 12.7 min (11-15), p < 0.05. Post-LTx, 1 pulmonary hypertensive patient required ECMO for PGD3. The mean group pO2/FiO2 ratio at 24 hours was 307.7 (240-507) with an ICU stay of 9.5 days (2-21) and ward stay of 21.5 days (11-76). All 8 survive at a mean of 311 days (10-573) with good performance status and lung function. In conclusion, the use of Maastricht category III lungs for human LTx is associated with acceptable early clinical outcomes.


Fast computation of static capacitance for periodic SAW transducers.
An efficient algorithm to compute the static capacitance of periodic SAW (surface acoustic wave) interdigital transducers is proposed. The method is based on a new formulation of the well-known relationship giving the capacitance as a linear combination of the charges induced on an infinite transducer for one-electrode excitation. Besides computational efficiency, an interesting physical interpretation of static capacitance results. The algorithm itself is also tailored to split-finger transducers.


[Isothiocyanate and vinyl thio-oxazolidone contents of rape seeds and rape seed oil].
Comparative studies on the isothiocyanate content of rape-seeds and rape-seed oil show that, apart from nearly 300 mg/100 g of vinyl thio-oxazolidone, rape-seeds contain almost 200--300 mg/100 g of isothiocyanates of which 3-butenyl isothiocyanate and 4-pentenyl isothiocyanate (ratio of 4:1) are the main components as evidenced thin-layer and gaschromatographically. Only about 1 mg/100 g of isothiocyanates are found in pressed rape-seed oil; and but circa 10 mg/100 g, in extracted rape-seed oil. 3-Butenyl isothiocyanate and 4-pentenyl isothiocyanate (ratio of 4:1) are once more the main components. Thioglycerides are not detected in the oil. Vinyl thio-oxazolidone is found only in extracted rape-seed oil (about 2 mg/100 g).


Physical linkage of metabolic genes in fungi is an adaptation against the accumulation of toxic intermediate compounds.
Genomic analyses have proliferated without being tied to tangible phenotypes. For example, although coordination of both gene expression and genetic linkage have been offered as genetic mechanisms for the frequently observed clustering of genes participating in fungal metabolic pathways, elucidation of the phenotype(s) favored by selection, resulting in cluster formation and maintenance, has not been forthcoming. We noted that the cause of certain well-studied human metabolic disorders is the accumulation of toxic intermediate compounds (ICs), which occurs when the product of an enzyme is not used as a substrate by a downstream neighbor in the metabolic network. This raises the hypothesis that the phenotype favored by selection to drive gene clustering is the mitigation of IC toxicity. To test this, we examined 100 diverse fungal genomes for the simplest type of cluster, gene pairs that are both metabolic neighbors and chromosomal neighbors immediately adjacent to each other, which we refer to as "double neighbor gene pairs" (DNGPs). Examination of the toxicity of their corresponding ICs shows that, compared with chromosomally nonadjacent metabolic neighbors, DNGPs are enriched for ICs that have acutely toxic LD50 doses or reactive functional groups. Furthermore, DNGPs are significantly more likely to be divergently oriented on the chromosome; remarkably, ∼40% of these DNGPs have ICs known to be toxic. We submit that the structure of synteny in metabolic pathways of fungi is a signature of selection for protection against the accumulation of toxic metabolic intermediates.


Household exposure to violence and human rights violations in western Bangladesh (II): history of torture and other traumatic experience of violence and functional assessment of victims.
Organised crime and political violence (OPV) and human rights violations have marred Bangladesh history since 1971. Little is known about the consequences for the oppressed population. This study describes the patterns of OPV and human rights violations in a disturbed area of Bangladesh and assesses the physical, emotional and social functioning of victims. A total of 236 of selected participants in a household survey in Meherpur district were recruited for a detailed study. Interviews and physical examinations were used to obtain information about history of torture and other cruel, inhuman or degrading treatment or punishment (TCIDTP), and about injuries, pain frequency and intensity. Handgrip strength and standing balance performance were measured. The "WHO-5 Well-being" scale was used to assess the subjective emotional well-being of study participants. The majority of the reported cases of TCIDTP occurred in 2000-2008, 51% of incidents occurred during winter; 32.0% between 20:00 and midnight. Police involvement was reported in 75% of cases. Incidents took place at victims' homes (46.7%), or at the police station, military camp, in custody or in prison (21.9%). Participants experienced 1-10 TCIDTP methods and reported 0-6 injury locations on their bodies; 77.5% reported having at least two injuries. Less than half of the participants were able to stand on one leg for 30 seconds. Only 7.5% of males aged 25-44 had handgrip strength in both hands exceeding average values for healthy people at the same age. Over 85% of participants scored low (<13) on the 25-point "WHO-5 Well-being" scale. The number of years since the TCIDTP event, pain frequency, the need to quit a job to take care of an injured family member, political involvement, personal conflicts and the fear of neighbourhood violence strongly affected emotional well-being. Good emotional well-being correlated with increased political and social participation. A detailed picture of characteristics of the victimisation is presented. The participants showed poor emotional well-being and reduced physical capacity. The results indicated that the simple and rapid method of assessment used here is a promising tool that could be used to monitor the quality and outcome of rehabilitation.


Consistency of long-term outcome of acute Rockwood grade III acromioclavicular joint separations after K-wire transfixation.
Surgical approach to acute Rockwood grade III acromioclavicular (AC) joint injuries demands satisfying and reliable treatment results of shoulder function in the long term. This study investigates the operative outcome of acute grade III AC joint separations after temporary K-wire transfixation of the AC joint over the years. We hypothesize, that the well-established temporary articular transfixation of acute Rockwood grade III AC joint dislocations with K-wires provides good and consistent functional outcome at long term. Seventy patients who underwent temporary articular transfixation of the AC joint followed by a standardized rehabilitation program and early physiotherapeutic exercising were divided into three follow-up cohorts. The treatment results were investigated 1 to 2 years (short-term, group A, n = 18), 3 to 5 years (mid-term, group B, n = 33), and 6 to 10 years (long-term, group C, n = 19) after surgical procedure. The outcome was measured using a standardized functional patient questionnaire including Constant score, ASES rating scale, SPADI, and XSMFA-D score. The results given in average and mean +/- SD were compared between the three cohorts by calculating the Kruskal-Wallis one way analysis for variance on ranks. Average patient age at time of surgical therapy was 37 (+/-11) years without significant difference between the three cohorts. Independent of follow-up period all patients demonstrated good functional treatment results in the long run expressed by an over all Constant score of 88 (+/-10) points, ASES rating scale of 29 (+/-3) points, SPADI of 3 (+/-9) points, XSMFA-D function score of 13 (+/-2) points, and XSMFA-D impairment score of 4 (+/-1) points, respectively. The comparison of the three follow-up groups proved no significant differences in outcome over a maximum follow-up period of up to 10 years. However, the longer the follow-up period, the tendency of the promising treatment outcome becomes more stable. Temporary K-wires fixation of acute Rockwood grade III AC joint separations enable good long-term results in shoulder function. The achieved functional outcome parameters reveal a high consistency in the long run over the years.


High risk of non-A non-B hepatitis after a first exposure to volunteer or commercial clotting factor concentrates: effects of prophylactic immune serum globulin.
After a first exposure to factor VIII concentrates, 9/9 British patients treated with U.S.A.-derived commercial products, and 10/12 treated with British volunteer (NHS) products, developed acute non-A, non-B (NANB) hepatitis. Hepatitis following commercial products was more severe, and of shorter incubation. High previous exposure to NHS blood products seemed to prevent NHS but not commercial factor VIII-induced hepatitis; the latter was also not attenuated by administration of U.S.A.-derived commercial immune serum globulin (ISG). After a first exposure to NHS factor IX concentrates without ISG, 4/4 patients developed short incubation NANB hepatitis; one also contracted prolonged incubation hepatitis B. One patient treated with ISG and factor IX of proven infectivity did not develop hepatitis, suggesting protection by ISG. Observed differences between concentrates might be attributable to their content of different NANB agents, but dose-related effects could provide alternative explanations. This data provides a basis for comparative assessment of new products of possible reduced infectivity in only small numbers of patients.


[Protein kinase activity of immunoglobulins in human blood plasma].
Protein kinase activity of the immunoglobulins (Ig) fractions from blood plasma of clinically healthy humans has been studied. IgA, IgG and IgM preparations have been obtained using column chromatography on sorbents with rabbit antibody to H-chains of human Ig. The level of 32P incorporation in casein in the presence of [gamma-32P]ATP was used to determine protein kinase activity of the Ig-fractions. The protein kinase activity of the preparation of IgA (but not IgG or IgM) was defined. The high-purified preparation of IgA for studing the protein kinase activity has been obtained. Three stages of purifications were used--the separation of plasma proteins by polyethylenglycol 6000, gel-filtration on the column with Toyopearl HW-60 Fine and affinity chromatography on the column containing rabbit antibody to H-chains of human IgA. It was revealed that the fraction of IgA possesses the casein phosphorylation activity. Heparin and trifluoperazine completely and partially inhibited protein kinase activity of IgA while spermidine did not render essential influence. On the basis of the obtained results the conclusion is made that the blood of clinical by healthy humans contains IgA possessing the protein kinase activity.


Mitochondrial disorders and drugs: what every physician should know.
Mitochondrial disorders are a group of metabolic conditions caused by impairment of the oxidative phosphorylation system. There is currently no clear evidence supporting any pharmacological interventions for most mitochondrial disorders, except for coenzyme Q10 deficiencies, Leber hereditary optic neuropathy, and mitochondrial neurogastrointestinal encephalomyopathy. Furthermore, some drugs may potentially have detrimental effects on mitochondrial dysfunction. Drugs known to be toxic for mitochondrial functions should be avoided whenever possible. Mitochondrial patients needing one of these treatments should be carefully monitored, clinically and by laboratory exams, including creatine kinase and lactate. In the era of molecular and 'personalized' medicine, many different physicians (not only neurologists) should be aware of the basic principles of mitochondrial medicine and its therapeutic implications. Multicenter collaboration is essential for the advancement of therapy for mitochondrial disorders. Whenever possible, randomized clinical trials are necessary to establish efficacy and safety of drugs. In this review we discuss in an accessible way the therapeutic approaches and perspectives in mitochondrial disorders. We will also provide an overview of the drugs that should be used with caution in these patients.


The transcription coactivator CBP is a dynamic component of the promyelocytic leukemia nuclear body.
The transcription coactivator and histone acetyltransferase CAMP response element-binding protein (CBP) has been demonstrated to accumulate in promyelocytic leukemia (PML) bodies. We show that this accumulation is cell type specific. In cells where CBP does not normally accumulate in PML bodies, it can be induced to accumulate in PML bodies through overexpression of either CBP or Pml, but not Sp100. Using fluorescence recovery after photobleaching, we demonstrate that CBP moves rapidly into and out of PML bodies. In contrast, Pml and Sp100 are relatively immobile in the nucleoplasm and within PML nuclear bodies. They possess the characteristics expected of proteins that would play a structural role in the integrity of these subnuclear domains. Our results are consistent with CBP being a dynamic component of PML bodies and that the steady-state level in these structures can be modulated by Pml.


No association between CTNNBL1 and episodic memory performance.
Polymorphisms in the gene encoding catenin-β-like 1 (CTNNBL1) were recently reported to be associated with verbal episodic memory performance--in particular, delayed verbal free recall assessed between 5 and 30 min after encoding--in a genome-wide association study on healthy young adults. To further examine the genetic effects of CTNNBL1, we tested for association between 455 single-nucleotide polymorphisms (SNPs) in or near CTNNBL1 and 14 measures of episodic memory performance from three different tasks in 1743 individuals. Probands were part of a population-based study of mentally healthy adult men and women, who were between 20 and 70 years old and were recruited as participants for the Berlin Aging Study II. Associations were assessed using linear regression analysis. Despite having sufficient power to detect the previously reported effect sizes, we found no evidence for statistically significant associations between the tested CTNNBL1 SNPs and any of the 14 measures of episodic memory. The previously reported effects of genetic polymorphisms in CTNNBL1 on episodic memory performance do not generalize to the broad range of tasks assessed in our cohort. If not altogether spurious, the effects may be limited to a very narrow phenotypic domain (that is, verbal delayed free recall between 5 and 30 min). More studies are needed to further clarify the role of CTNNBL1 in human memory.


Rapid, dose-dependent elimination of phenol across the gills, and slow elimination of phenyl sulfate in the urine of phenol-dosed lobsters, Homarus americanus.
Although lobsters are known to metabolize lipophilic organic compounds by monooxygenation, little is known of the fate of the hydroxylated metabolites. Single doses of [14C]phenol, 0.019 to 2.8 mg/kg, were administered intrapericardially to groups of lobsters. Hemolymph was sampled serially from appendage joints and analyzed for radioactivity and chemical composition. Separate groups of lobsters were dissected at 0.5, 4, and 24 hr after the 0.1-mg/kg dose to collect urine and tissue samples. Tank water was collected at 0.5 hr and analyzed. Phenol concentrations decreased rapidly in hemolymph (alpha t1/2 = 8.7 min, beta t1/2 = 14.0 min) and part of the dose was excreted through gills into tank water as parent phenol in the first 30 min. The percentage of each dose excreted through the gills increased with increasing dose up to greater than 90% at greater than 2 mg/kg. The phenol that was not excreted through gills was rapidly conjugated with sulfate in the antennal glands and possibly other sites. In both male and female lobsters, phenyl sulfate was eliminated from hemolymph much more slowly than parent phenol. The terminal elimination half-life of phenyl sulfate was slower in females (t1/2 = 11.9 hr) than in males (t1/2 = 6.3 hr). The [14C] present in urine collected 24 hr after the dose consisted primarily of phenyl sulfate (greater than 97%) with traces of phenyl beta-D-glucoside (0.1-3%). Thus, in the lobster, metabolism of phenol to polar conjugates did not enhance elimination from the animal.


Teaching multiple approaches to management to facilitate prosocial and environmental well-being.
Friedman's maxim "The social responsibility of business is to increase its profits" (p. 32) has shaped what managers consider effective management. This Financial Bottom Line approach to management has been challenged by both Positive Organizational Scholarship (POS) and Critical Management Studies (CMS). POS highlights how enhancing prosocial and other nonfinancial considerations can increase profits, consistent with the current dominant Triple Bottom Line approach. In contrast, CMS tends to critique any approach that seeks to maximize profits by creating dysfunctional power symmetries and marginalization. This study introduces a third option, the Social and Ecological Thought approach, which promotes maximizing social and ecological well-being while remaining financially viable. A longitudinal pre-post intervention in a sample of undergraduate management students showed that teaching multiple approaches to management-Financial Bottom Line, Triple Bottom Line, and Social and Ecological Thought-resulted in learners becoming less likely to espouse profit-related goals (e.g. to maximize efficiency, productivity, profitability) and more likely to identify nonfinancial ones (e.g. extra-organizational prosociality and reduction of marginalization) when characterizing effective management. However, the results did not support predictions regarding intra-organizational prosociality and marginalization, or power asymmetries. We discuss implications for pedagogy and the future development of POS and CMS.


Prevention of recurrent spontaneous abortions by leukocyte transfusions.
One hundred and thirty-nine couples referred because of recurrent abortions with no obvious cause were assessed for genetic similarity using the HLA major histocompatibility system. Comparison with 103 fertile control couples demonstrated that a much higher proportion of couples in the abortion group shared two or more HLA antigens. Using this criterion, 44 wives out of the 139 couples referred, when compared with a child-bearing group, appeared to share a greater than expected number of histocompatibility antigens and were therefore considered suitable for treatment. Twenty-eight wives have received treatment with white cell infusions from erythrocyte-compatible donors and so far they have delivered 17 babies plus 2 second babies. Another 3 wives are pregnant beyond their previous dates for abortions (1 first and 2 second pregnancies). There have been 5 failures (4 first pregnancy and 1 second pregnancy); one of these was treated a second time and has now successfully delivered. Seven couples are awaiting conception. Of the patients who have become pregnant, 81.5% have had successful deliveries. No adverse transfusion reactions have been observed.


Canned sea fish marketed in Serbia: their zinc, copper, and iron levels and contribution to the dietary intake.
The aim of this study was to determine the levels of Zn, Cu, and Fe in three canned fish species marketed Serbia to see if they meet recommended daily intake requirements or exceed safety limits. We collected a total of 207 samples of canned tuna, sardine, and mackerel, in oil or tomato sauce and analysed them with inductively coupled plasma mass spectrometry (ICP-MS) after acid digestion. The highest levels were obtained for Zn (15.1 mg kg-1) and Cu (1.37 mg kg-1) in sardine in oil and tomato sauce, respectively, and for Fe (18.98 mg kg-1) in mackerel in tomato sauce. Our results keep within the ranges reported by several national food databases and available literature data, with a few exceptions. Our findings also single out canned sardines as the richest source of the three essential elements combined. The estimated daily intake (EDI) of the three essential elements, however, was subpar, and ranged between 0.14 % and 0.72 % of the recommended dietary allowance (RDA) for Zn, Cu, and Fe.


Tuberculosis of the esophagus.
We report a case of a patient with esophageal tuberculosis, a very uncommon form of extrapulrhonar tuberculosis. Initially, because of constitutional symptomatology and radiological findings of mediastinal lymph node enlargement, lymphoma was considered. However, the endoscopic findings of ulcerative masses and a sinus tract revealed by esophagram were suspicious of tuberculous origin. Diagnosis was achieved after bacterial examination of smear samples from esophageal ulcers that revealed bacillus tuberculous and histological demonstration of caseating granulomas in cervical lymph nodes. Tuberculous mediastinal lymphadenitis was thought to be source of the spread to esophagus.The patient was successfully treated with a three antituberculous drugs regimen. In spite of its rarity, even in patients without risk factors, the diagnosis would be considered in the differential diagnosis of uncertain esophageal lesions.


The effectiveness of police custody assessments in identifying suspects with intellectual disabilities and attention deficit hyperactivity disorder.
Intellectual Disabilities (ID) and Attention Deficit Hyperactivity Disorder (ADHD) are recognized psychological vulnerabilities in police interviews and court proceedings in England and Wales. The aims of this study were to investigate: (a) the prevalence of ID and/or ADHD among suspects detained at a large London metropolitan police station and their relationship with conduct disorder (CD), (b) the impact of their condition on police staff resources, (c) the effectiveness of current custody assessment tools in identifying psychological vulnerabilities, and (d) the use of 'Appropriate Adults' in interviews. A total of 200 individuals in a police custody suite were interviewed and screened for ID, ADHD (current symptoms) and CD. The screening rates for these three disorders were 6.7%, 23.5% and 76.3%, respectively. ADHD contributed significantly to increased requests being made of staff after controlling for CD and duration of time in custody. This is a novel finding. Reading and writing difficulties and mental health problems were often identified from the custody risk assessment tools, but they were not used effectively to inform on the need for the use of an Appropriate Adult. The frequency with which Appropriate Adults were provided to support detainees in police interviews (4.2%) remains almost identical to that found in a similar study conducted 20 years previously. The current findings suggest that in spite of reforms recently made in custodial settings, procedures may not have had the anticipated impact of improving safeguards for vulnerable suspects. Detainees with ID and ADHD require an Appropriate Adult during police interviews and other formal custody procedures, which they commonly do not currently receive. The findings of the current study suggest this may be due, in large part, to the ineffective use of risk-assessment tools and healthcare professionals, which represent missed opportunities to identify such vulnerabilities.


[Electrophysiologic study and ablation therapy in idiopathic paroxystic atrial fibrillation].
To analyze the results of radiofrequency catheter ablation (RFCA) of the pulmonary veins (PV) in patients with paroxysmal atrial fibrillation (PAF). We describe 4 patients (38 +/- 12 years, interval 8-52; 11 men) with symptomatic PAF, refractory to antiarrhythmic drugs. Special mapping catheters were used and ablation was performed at the ostium/antrum of those veins with abnormal electrical activity (AEA). AEA in one or more PV was identified in 13 patients (86%); in one patient AEA was also found in the superior vena cava (6.6%). One procedure was complicated by unstable ventricular tachycardia and was notfinished. Success was accomplished in 10, in 5 after the first ablation, in 4 after the second, and in one after a third procedure. One patient had pericarditis with a small pericardial effusion that did not require intervention. RFCA is a useful and relatively safe procedure for the treatment of PAF and the only one with curative potential. The long-term rate of success (with or without antiarrhythmics) in this series was 71%. These results justify catheter ablation in selected patients with symptomatic PAF unresponsive to medical treatment.


Grape ASR-Silencing Sways Nuclear Proteome, Histone Marks and Interplay of Intrinsically Disordered Proteins.
In order to unravel the functions of ASR (Abscisic acid, Stress, Ripening-induced) proteins in the nucleus, we created a new model of genetically transformed grape embryogenic cells by RNAi-knockdown of grape ASR (VvMSA). Nuclear proteomes of wild-type and VvMSA-RNAi grape cell lines were analyzed by quantitative isobaric tagging (iTRAQ 8-plex). The most significantly up- or down-regulated nuclear proteins were involved in epigenetic regulation, DNA replication/repair, transcription, mRNA splicing/stability/editing, rRNA processing/biogenesis, metabolism, cell division/differentiation and stress responses. The spectacular up-regulation in VvMSA-silenced cells was that of the stress response protein VvLEA D-29 (Late Embryogenesis Abundant). Both VvMSA and VvLEA D-29 genes displayed strong and contrasted responsiveness to auxin depletion, repression of VvMSA and induction of VvLEA D-29. In silico analysis of VvMSA and VvLEA D-29 proteins highlighted their intrinsically disordered nature and possible compensatory relationship. Semi-quantitative evaluation by medium-throughput immunoblotting of eighteen post-translational modifications of histones H3 and H4 in VvMSA-knockdown cells showed significant enrichment/depletion of the histone marks H3K4me1, H3K4me3, H3K9me1, H3K9me2, H3K36me2, H3K36me3 and H4K16ac. We demonstrate that grape ASR repression differentially affects members of complex nucleoprotein structures and may not only act as molecular chaperone/transcription factor, but also participates in plant responses to developmental and environmental cues through epigenetic mechanisms.


Parametric face drawings: A demographically diverse and customizable face space model.
We introduce a novel face space model-parametric face drawings (or PFDs)-to generate schematic, though realistic, parameterized line drawings of faces based on the statistical distribution of human facial features. A review of existing face space models (including FaceGen Modeller, Synthetic Faces, MPI, and active appearance model) indicates that current models are constrained by their reliance on ethnically homogeneous face databases. This constraint has led to negative consequences for underrepresented populations, such as impairments in automatized identity recognition of certain demographic groups. Our model is based on a demographically diverse sample of 400 faces (200 female, 200 male; 100 East Asian/Pacific Islander, 100 Latinx/Hispanic, 100 black/African-American, and 100 white/Caucasian) compiled from several face databases (including FERET face recognition technology and the Chicago Face Database). Each front-view face image is manually coded with 85 landmark points that are then normalized and rendered with MATLAB (MathWorks, Natick, MA) tools to produce a smooth, parameterized face line drawing. We present data from two behavioral experiments to validate our model and demonstrate its applicability. In Experiment 1 we show that PFDs produce a reliable "inversion effect" in short-term recognition, a hallmark of holistic processing. In Experiment 2, we conduct a celebrity recognition task, comparing performance on PFDs to performance on untextured renderings from FaceGen Modeller. Participants successfully recognized approximately 50% of celebrity faces based on the PFD models, comparable to performance based on FaceGen Modeler (also 50% correct). We highlight a range of potential applications of our model, list some limitations, and provide MATLAB resources for researchers to utilize our face space, including the ability to customize the demographic makeup of the face space, add new faces, and produce morphs and caricatures.