Natural hybridization between divergent lineages in a selfing hermaphroditic fish.
By definition, mating between individuals is infrequent in highly selfing organisms, and so too, therefore, hybridization should be rare between genetically divergent lineages in predominantly self-fertilizing species. Notwithstanding these expectations, here we report a remarkable case of natural hybridization between highly diverged phylogeographic lineages of the mangrove rivulus, a small killifish that reproduces predominantly by self-fertilization and typically is found as highly homozygous lines in most parts of its extensive geographical range. Two distinctive genetic lineages (Kryptolebias marmoratus and a 'Central clade' closely related to K. hermaphroditus) previously were not known in sympatry, but were found by us to co-occur on San Salvador, Bahamas. Genetic analyses of a mitochondrial and multiple nuclear markers determined the direction of a cross producing a hybrid fish. Furthermore, we show that this hybrid individual was viable, as it successfully reproduced by self-fertilization for two generations. Additional sampling of this population will be necessary to determine if backcrossing of hybrids to the parental lineages occurs in nature and to analyse whether such backcross progeny are viable. Application of the biological species concept (BSC) is traditionally difficult in clonally reproducing organisms. Our results show that although mangrove rivulus fish are mostly highly selfing in nature (resulting in isogenic, effectively clonal and homozygous progeny), classification within this taxonomic complex need not be incompatible with the BSC.


Clinical test performance of distortion-product otoacoustic emissions using new stimulus conditions.
To determine whether new stimulus parameters, which have been shown to produce large distortion-product otoacoustic emission (DPOAE) levels in a group of normal-hearing listeners (Neely et al. 2005; Johnson et al. 2006), result in more accurate identification of auditory status and more accurate predictions of behavioral threshold than traditional stimulus conditions. DPOAE input/output (I/O) functions for eight f2 frequencies ranging from 0.7 to 8 kHz were recorded from 96 ears with normal hearing and 226 ears with sensorineural hearing losses ranging from mild to profound. The primary-level differences and primary-frequency ratios were set according to the stimulus relations developed by Johnson et al. (2006). The accuracy of the dichotomous decision task (area under the relative operating characteristic curve [AROC]) for these new stimulus conditions was evaluated as a function of L2 and was compared with previous reports in the literature where traditional stimuli were used (Stover et al. 1996). Here, traditional stimuli are defined as L1 = L2 + 10 and f2/f1 = 1.22 for all L2 and f2 values. In addition to I/O functions, DPgrams with L2 = 55-dB sound pressure level (SPL) and f2 ranging from 0.7 to 8 kHz were recorded for each subject using the traditional stimuli. This provided a direct within-subject comparison of AROC for moderate-level stimuli when the new and traditional stimuli were used. Finally, the accuracy with which DPOAE thresholds predicted behavioral thresholds was evaluated in relation to previous reports in the literature for two definitions of DPOAE threshold, one where the entire I/O function was used to make the prediction and a second where the lowest L2 producing a signal to noise ratio > or =3 dB was used. There was no evidence that the new stimuli improved the accuracy with which auditory status was identified from DPOAE responses. With both the new and traditional stimuli, moderate stimulus levels (L2 = 40- to 55-dB SPL) resulted in the most accurate identification of auditory status. When L2 = 55-dB SPL, the new stimuli produced AROC values that were equivalent to those observed with traditional stimuli. The new stimuli resulted in more accurate prediction of behavioral threshold for several f2 values when using the entire I/O function, although the effect was small. Furthermore, using the entire I/O function to predict behavioral threshold results in more accurate predictions of behavioral threshold than using the signal to noise ratio definition, although this approach can be applied to a smaller percentage of ears. The new stimuli that had been shown previously to produce large DPOAE levels in normal-hearing listeners (Neely et al. 2005; Johnson et al. 2006) do not result in more accurate identification of auditory status and have only a small positive effect on the prediction of behavioral threshold.


Treadmill Walking Maintains Dual-task Gait Performance and Reduces Frontopolar Cortex Activation in Healthy Adults.
Studies examining dual-task gait (DTG) have used varying conditions such as overground or treadmill walking, however it is not known whether brain activation patterns differ during these conditions. Therefore, this study compared oxyhaemoglobin (O2Hb) responses of the prefrontal cortex (PFC) during overground and treadmill walking. A total of 30 participants (14M/16F) were recruited in a randomized crossover study comparing overground and treadmill walking under single- and dual-task (STG and DTG) conditions. The DTG consisted of performing walking and cognitive (serial subtraction by 7's) tasks concurrently. A portable 24-channel functional near-infrared spectroscopy system was placed over the PFC, corresponding the left and right dorsolateral PFC and frontopolar cortices (DLPFC and FPC) during overground and treadmill STG and DTG. Results showed a reduction in gait speed during DTG compared to STG on overground but not treadmill walking, while cognitive performance was maintained during DTG on both overground and treadmill walking. A reduction in O2Hb was seen in the FPC during DTG compared to a cognitive task only, and on the treadmill compared to overground walking. Increased activation was seen in the left and right DLPFC during DTG but did not differ between treadmill and overground walking. Our results support the concept of improved gait efficiency during treadmill walking, indicated by the lack of change in STG and DTG performance and concomitant with a reduction in FPC activation. These findings suggest different neural strategies underpinning treadmill and overground walking, which should be considered when designing gait assessment and rehabilitation interventions.


Continuous Positive Airway Pressure Effect on Progression of Retinal Disease in Patients with Sleep Apnea and Nonproliferative Diabetic Retinopathy: A Randomized Clinical Trial.
Rationale: Obstructive sleep apnea (OSA) is associated with impaired glycemic control and a higher risk of vascular complications, such as diabetic retinopathy. However, the effect of apnea-hypopnea suppression on retinal disease progression is unclear. Objectives: To evaluate the efficacy and safety of continuous positive airway pressure (CPAP) for the reduction of retinal lesions in patients with non-proliferative diabetic retinopathy (NPDR) and OSA. Methods: This open-label, parallel-group, randomized controlled trial was conducted between October 2016 and February 2020 at a university hospital in Spain. The date of final follow-up was March 2, 2021. Eighty-three patients with OSA and mild to moderate NPDR receiving stable treatment were randomized to receive CPAP and usual care (43 patients with 79 available eyes) or usual care alone (40 patients with 67 available eyes) for 52 weeks. The primary outcomes were the change in the percentage of eyes with retinal exudates and the number of retinal microhemorrhages from baseline to week 52. We also assessed the effects of both interventions on retinal thickness by means of optical coherence tomography, serum concentrations of glycated hemoglobin, blood pressure, lipid concentrations, sleepiness, and quality of life. Results: Fifty-two weeks of CPAP treatment was associated with reductions from baseline in the percentage of eyes with hard exudates (overall difference, -21.7%; P = 0.035) and in optical coherence tomography indices of retinal edema, including central subfield thickness and cube volume. However, in patients who met prespecified criteria for CPAP adherence, treatment was also associated with a higher number of retinal microhemorrhages at 52 weeks (intergroup adjusted difference, 6.0 [95% confidence interval, 0.6-11.5]; P = 0.029), which was directly related to prescribed pressure levels. CPAP treatment also improved glycemic control, sleepiness, and general health-related quality of life. Conclusions: In patients with OSA and NPDR, long-term CPAP treatment in addition to usual care may result in slower progression of retinal disease, although it could also induce an increase in retinal microhemorrhages. Clinical trial registered with www.clinicaltrials.gov (NCT02874313).


Gallbladder cancer: epidemiology and genetic risk associations.
Gallbladder cancer (GBC) is a form of hepatobiliary malignancy that develops from the mucosal lining of the gallbladder. The early development of gallbladder cancer is usually asymptomatic and gallbladder cancer has a high propensity to metastatic dissemination, thus most patients are diagnosed at intermediate to advanced stages for which there is no curative treatment. Consequently, gallbladder cancer is highly lethal. Though the overall global incidence of gallbladder cancer is low, there is marked geographic variation and ethnic communities in Asia as well as Native American populations in both North and South America are affected disproportionately. This article provides a comprehensive overview of the current epidemiology and risk and protective factors associated with gallbladder cancer development. In addition, the current knowledge on environmental and genetic risk associations for gallbladder cancer and the need for additional large-scale genome wide association studies (GWAS) are discussed.


Taxonomic implications of Rhodotorula rubra isolates from polluted sea water in Rio de Janeiro, Brazil.
Sixty two strains of Rhodotorula rubra which were all isolated from marine and estuarine waters of Rio de Janeiro were found variable for 19 to 32 carbon assimilation tests used in yeast taxonomy. Two R. rubra strains which had latent assimilation of maltose and melizitose appeared to be intermediate with R. pilimanae. Strains of R. glutinis var dairenensis which differed from R. rubra only by weak assimilation of nitrate appeared to be intermediated between these two species. Our physiological tests suggested that R. rubra, R. pilimanae, and part of R. glutinis should be combined and this was supported by DNA base composition and coezyme Q data existing in the literature.


Disrupted brain functional network in internet addiction disorder: a resting-state functional magnetic resonance imaging study.
Internet addiction disorder (IAD) is increasingly recognized as a mental health disorder, particularly among adolescents. The pathogenesis associated with IAD, however, remains unclear. In this study, we aim to explore the encephalic functional characteristics of IAD adolescents at rest using functional magnetic resonance imaging data. We adopted a graph-theoretic approach to investigate possible disruptions of functional connectivity in terms of network properties including small-worldness, efficiency, and nodal centrality on 17 adolescents with IAD and 16 socio-demographically matched healthy controls. False discovery rate-corrected parametric tests were performed to evaluate the statistical significance of group-level network topological differences. In addition, a correlation analysis was performed to assess the relationships between functional connectivity and clinical measures in the IAD group. Our results demonstrate that there is significant disruption in the functional connectome of IAD patients, particularly between regions located in the frontal, occipital, and parietal lobes. The affected connections are long-range and inter-hemispheric connections. Although significant alterations are observed for regional nodal metrics, there is no difference in global network topology between IAD and healthy groups. In addition, correlation analysis demonstrates that the observed regional abnormalities are correlated with the IAD severity and behavioral clinical assessments. Our findings, which are relatively consistent between anatomically and functionally defined atlases, suggest that IAD causes disruptions of functional connectivity and, importantly, that such disruptions might link to behavioral impairments.


Screening for pancreatic cancer in familial high-risk individuals: A systematic review.
To analyze the benefits and harms of pancreatic cancer screening in familial high-risk individuals (HRIs). Studies were identified by searching PubMed, EBSCO, ClinicalTrials.gov and the Cochrane database from database inception to June 2014. We also obtained papers from the reference lists of pertinent studies and systematic reviews. English-language trials and observational studies were searched. The key words used as search terms were "screening" and "surveillance". Cost-effectiveness, diagnostic rate, survival rate, mortality and adverse events were the outcomes of interest. Age, sex, lifestyle and other confounding factors were also considered. However, anticipating only a few of these studies, we also included observational studies with or without control groups. We also included studies concerning the anxiety associated with pancreatic cancer risk and other psychological changes in familial HRIs. We extracted details on study design, objectives, population characteristics, inclusion criteria, year of enrollment, method of screening, adjusted and unadjusted mortality, cost-effectiveness and adverse events from the included studies. Studies were assessed using the Reporting of Observational studies in Epidemiology (STROBE) checklist. Sixteen studies on pancreatic cancer screening were included. Five studies included control groups, nine were observational studies without control groups, and the other two studies investigated the worry associated with pancreatic cancer risk. We found that pancreatic cancer screening resulted in a high curative resection rate (60% vs 25%, P = 0.011), longer median survival time (14.5 mo vs 4 mo, P < 0.001), and higher 3-year survival rate (20% vs 15.0%, P = 0.624). We also found that familial HRIs had a higher diagnostic rate of pancreatic tumors than controls (34% vs 7.2%, P < 0.001). In patients who underwent regular physical examinations, more stage I pancreatic cancers were observed (19% vs 2.6%, P = 0.001). In addition, endoscopic ultrasonography, which was the main means of detection, diagnosed 64.3% of pancreatic cancers. In comparison, endoscopic retrograde cannulation of the pancreas, magnetic resonance imaging, and computed tomography diagnosed 28.6%, 42.9%, and 21.4%, respectively. For mass lesions, instant surgery was recommended because of the beneficial effects of post-operative chemotherapy. However, in patients with intraductal papillary mucinous neoplasms, we did not find a significant difference in outcome between surgery and follow-up without treatment. Moreover, pancreatic cancer screening in familial HRIs had a greater perceived risk of pancreatic cancer (P < 0.0001), higher levels of anxiety regarding pancreatic cancer (P < 0.0001), and increased economic burden. Pancreatic cancer screening in familial HRIs is associated with a higher detection rate and longer survival, although screening may influence psychological function and increase the economic burden.


Effect of antibiotics and antimicrobial peptides on single protein motility.
Following the movement of individual molecules of a bacterial surface protein in vivo we investigated the effects of antibiotics and antimicrobial peptides on protein motility and membrane structure. In previous work we engineered the lambda-receptor of Escherichia coli such that less than one receptor per cell is in vivo biotinylated and can bind to a streptavidin coated bead. Such a bead served as a handle for the optical tweezers to follow the motion of an individual receptor. In an un-perturbed living cell the lambda-receptor performs a confined diffusive motion. The lambda-receptor links to the peptidoglycan layer, and indeed, a perturbation of the peptidoglycan layer had a pronounced effect on the motility of the receptor: The motility significantly decreases upon treatment with vancomycin or ampicillin, to study the effect of vancomycin we used strains with increased membrane permeability. As the motility of an individual receptor was monitored over an extended amount of time we were able to observe a temporal evolution of the action of vancomycin. Antimicrobial peptides (AMPs) are alternatives to conventional antibiotics in the treatment of bacterial infections. Therefore, we also investigated the effect of the toxic AMP polymyxin B (PMB) which targets both the outer and inner membranes and kills the organism. PMB significantly decreased the motility of the lambda-receptor. On the basis of these findings we confirm that the lambda-receptor is firmly attached to the peptidoglycan layer, and that an antibiotic or AMP mediated destruction of the dynamic peptidoglycan synthesis decreases the receptor motion.


IDS conversions to for-profit status: structuring the deal.
Not-for-profit integrated delivery systems (IDSs) may convert assets to for-profit status in a variety of ways, but typically choose from three basic conversion structures: sale of assets, joint ventures, and lease or management agreements. To select the optimal conversion structure, not-for-profit IDS executives should understand the forces driving their organization's desire or need to effect such a conversion and examine the legal, business, and political implications of each option in light of the organization's particular circumstances.


Structure-function analysis of CCL28 in the development of post-viral asthma.
CCL28 is a human chemokine constitutively expressed by epithelial cells in diverse mucosal tissues and is known to attract a variety of immune cell types including T-cell subsets and eosinophils. Elevated levels of CCL28 have been found in the airways of individuals with asthma, and previous studies have indicated that CCL28 plays a vital role in the acute development of post-viral asthma. Our study builds on this, demonstrating that CCL28 is also important in the chronic post-viral asthma phenotype. In the absence of a viral infection, we also demonstrate that CCL28 is both necessary and sufficient for induction of asthma pathology. Additionally, we present the first effort aimed at elucidating the structural features of CCL28. Chemokines are defined by a conserved tertiary structure composed of a three-stranded β-sheet and a C-terminal α-helix constrained by two disulfide bonds. In addition to the four disulfide bond-forming cysteine residues that define the traditional chemokine fold, CCL28 possesses two additional cysteine residues that form a third disulfide bond. If all disulfide bonds are disrupted, recombinant human CCL28 is no longer able to drive mouse CD4+ T-cell chemotaxis or in vivo airway hyper-reactivity, indicating that the conserved chemokine fold is necessary for its biologic activity. Due to the intimate relationship between CCL28 and asthma pathology, it is clear that CCL28 presents a novel target for the development of alternative asthma therapeutics.


The thorax musculature of Anisoptera (Insecta: Odonata) nymphs and its evolutionary relevance.
Among the winged insects (Pterygota) the Odonata (dragon- and damselflies) are special for several reasons. They are strictly aerial predators showing remarkable flight abilities and their thorax morphology differs significantly from that of other Pterygota in terms of the arrangement and number of muscles. Even within one individual the musculature is significantly different between the nymphal and adult stage. Here we present a comparative morphological investigation of the thoracic musculature of dragonfly (Anisoptera) nymphs. We investigated representatives of the Libellulidae, Aeshnidae and Cordulegasteridae and found 71 muscles: 19 muscles in the prothorax, 26 in the mesothorax and 27 in the metathorax. Nine of these muscles were previously unknown in Odonata, and for seven muscles no homologous muscles could be identified in the neopteran thorax. Our results support and extend the homology hypotheses for the thoracic musculatures of Odonata and Neoptera, thus supplementing our understanding of the evolution of Pterygota and providing additional characters for phylogenetic analyses comprising all subgroups of Pterygota.


Coke formation and carbon atom economy of methanol-to-olefins reaction.
The methanol-to-olefins (MTO) process is becoming the most important non-petrochemical route for the production of light olefins from coal or natural gas. Maximizing the generation of the target products, ethene and propene, and minimizing the production of byproducts and coke, are major considerations in the efficient utilization of the carbon resource of methanol. In the present work, the heterogeneous catalytic conversion of methanol was evaluated by performing simultaneous measurements of the volatile products generated in the gas phase and the confined coke deposition in the catalyst phase. Real-time and complete reaction profiles were plotted to allow the comparison of carbon atom economy of methanol conversion over the catalyst SAPO-34 at varied reaction temperatures. The difference in carbon atom economy was closely related with the coke formation in the SAPO-34 catalyst. The confined coke compounds were determined. A new type of confined organics was found, and these accounted for the quick deactivation and low carbon atom economy under low-reaction-temperature conditions. Based on the carbon atom economy evaluation and coke species determination, optimized operating conditions for the MTO process are suggested; these conditions guarantee high conversion efficiency of methanol.


[Glucose transport inhibition in human erythrocytes by calmodulin antagonists].
Calmodulin antagonists (tryphtazin, lidocaine, dykain, palmitate) inhibit glucose transport from human erythrocytes. Glucose efflux inhibition is proportional to the concentration of antagonists in the medium and is of uncompetitive character. It is accompanied by a decrease in the maximum transport rate with the unchanged constant of dissociation in the complex: carrier-sugar. Calcium ionophores A23187 and divaleryldibenzo-18-crown-6 eliminated the inhibiting effect of pharmacological agents on glucose transport. The authors think that the glucose transport inhibition under the influence of calmodulin antagonists may be realized through the calmodulin-dependent chain inhibition under the influence of calmodulin antagonists in the carbohydrate transport system.


Hyperphagia during lactation: satiety response to CCK and growth of the pancreas.
Cholecystokinin (CCK) secreted from the duodenum during feeding has been shown to elicit satiety and stimulate growth of the pancreas in addition to affecting gastrointestinal function. In previous experiments hyperphagic Zucker obese rats were less sensitive to the effects of CCK on satiety and had a smaller pancreas than normal-weight rats. In the present experiments with hyperphagic lactating Zucker rats, the food intake response to exogenously administered CCK and the size and composition of the pancreas were measured. Food intakes after a 2-h fast were not decreased by 4.0 or 8.0 micrograms/kg CCK-8 during wk 1, 2, or 3 of lactation. However, in the same rats 2 wk after pups were weaned, 4.0 and 8.0 micrograms/kg CCK-8 decreased food intake 32% (2.1 +/- 0.4 vs. 3.1 +/- 0.3 g, paired t = 2.33, P less than 0.03) and 52% (1.5 +/- 0.2 vs. 3.1 +/- 0.5 g, paired t = 3.48, P less than 0.006). On day 18 of lactation, pancreas weight was increased 41% (1.38 +/- 0.05 vs. 0.98 +/- 0.02 g, paired t = 2.68, P less than 0.02) and contents of DNA, RNA, and protein were increased 57, 57, and 73%, respectively. Thus, hyperphagia in lactating female rats was associated with 1) decreased sensitivity to the satiety effect of CCK similar to that in hyperphagic obese rats and 2) hypertrophy of the pancreas in contrast to decreased pancreas size in obese rats.


Written distractor words influence brain activity during overt picture naming.
Language production requires multiple stages of processing (e.g., semantic retrieval, lexical selection), each of which may involve distinct brain regions. Distractor words can be combined with picture naming to examine factors that influence language production. Phonologically-related distractors have been found to speed picture naming (facilitation), while slower response times and decreased accuracy (interference) generally occur when a distractor is categorically related to the target image. However, other types of semantically-related distractors have been reported to produce a facilitative effect (e.g., associative, part-whole). The different pattern of results for different types of semantically-related distractors raises the question about how the nature of the semantic relation influences the effect of the distractor. To explore the nature of these semantic effects further, we used functional MRI to examine the influence of four types of written distractors on brain activation during overt picture naming. Distractors began with the same sound, were categorically-related, part of the object to be named, or were unrelated to the picture. Phonologically-related trials elicited greater activation than both semantic conditions (categorically-related and part-whole) in left insula and bilateral parietal cortex, regions that have been attributed to phonological aspects of production and encoding, respectively. Semantic conditions elicited greater activation than phonological trials in left posterior MTG, a region that has been linked to concept retrieval and semantic integration. Overall, the two semantic conditions did not differ substantially in their functional activation which suggests a similarity in the semantic demands and lexical competition across these two conditions.


Global eQTL mapping reveals the complex genetic architecture of transcript-level variation in Arabidopsis.
The genetic architecture of transcript-level variation is largely unknown. The genetic determinants of transcript-level variation were characterized in a recombinant inbred line (RIL) population (n = 211) of Arabidopsis thaliana using whole-genome microarray analysis and expression quantitative trait loci (eQTL) mapping of transcript levels as expression traits (e-traits). Genetic control of transcription was highly complex: one-third of the quantitatively controlled transcripts/e-traits were regulated by cis-eQTL, and many trans-eQTL mapped to hotspots that regulated hundreds to thousands of e-traits. Several thousand eQTL of large phenotypic effect were detected, but almost all (93%) of the 36,871 eQTL were associated with small phenotypic effects (R(2) < 0.3). Many transcripts/e-traits were controlled by multiple eQTL with opposite allelic effects and exhibited higher heritability in the RILs than their parents, suggesting nonadditive genetic variation. To our knowledge, this is the first large-scale global eQTL study in a relatively large plant mapping population. It reveals that the genetic control of transcript level is highly variable and multifaceted and that this complexity may be a general characteristic of eukaryotes.


The usefulness of NICE guidance in practice: different perspectives of managers, clinicians, and patients.
The UK National Institute for Health and Clinical Excellence (NICE) has been widely hailed as an international leader in health technology assessment. The objectives of its guidance are to ensure uniformity in healthcare provision, and promote a systematic and accountable way to allocate resources. However, research relating to the implementation of guidance is limited, and little is known about how it influences decision making at the consultation level or how useful it is to individual patients. In-depth interviews were undertaken with professionals involved in healthcare provision at the community level, and with clinical professionals and patients providing or receiving care for morbid obesity and breast cancer (n = 52). Although NICE guidance was generally well-regarded, in practice it was of more importance and usefulness to managerial than clinical professionals. Clinicians used a patchy approach to implementation depending on whether recommendations accorded with their personal interpretation of the evidence available, and whether funding was available locally. Many patients had not heard of NICE, and clinical professionals did not alert them to its existence. Even where patients knew about relevant guidance, they were rarely able to use it to assert their right to treatment. These findings challenge the perception that NICE guidance results in consistent and accountable decision making, and the limited accessibility and usefulness of guidance to patients suggests more information and support is needed at the point of provision if these objectives are to be achieved.


Coagulation tests on capillary blood. A screening procedure for use in small children.
A method of investigating the coagulation mechanism is described.Results obtained by this procedure are compared with those of tests carried out on venous blood obtained simultaneously from normal subjects and patients with a variety of clotting defects. Good correlation was found between the results of P and P tests on venous and capillary blood, and also between thromboplastin screening tests on capillary blood and antihaemophilic and Christmas factor levels. The methods described have proved reliable as a pre-operative screening procedure in routine use over a period of nearly two years.


Computer literacy and attitudes towards e-learning among first year medical students.
At the Medical University of Vienna, most information for students is available only online. In 2005, an e-learning project was initiated and there are plans to introduce a learning management system. In this study, we estimate the level of students' computer skills, the number of students having difficulty with e-learning, and the number of students opposed to e-learning. The study was conducted in an introductory course on computer-based and web-based training (CBT/WBT). Students were asked to fill out a questionnaire online that covered a wide range of relevant attitudes and experiences. While the great majority of students possess sufficient computer skills and acknowledge the advantages of interactive and multimedia-enhanced learning material, a small percentage lacks basic computer skills and/or is very skeptical about e-learning. There is also a consistently significant albeit weak gender difference in available computer infrastructure and Internet access. As for student attitudes toward e-learning, we found that age, computer use, and previous exposure to computers are more important than gender. A sizable number of students, 12% of the total, make little or no use of existing e-learning offerings. Many students would benefit from a basic introduction to computers and to the relevant computer-based resources of the university. Given to the wide range of computer skills among students, a single computer course for all students would not be useful nor would it be accepted. Special measures should be taken to prevent students who lack computer skills from being disadvantaged or from developing computer-hostile attitudes.


Women's adjustment trajectories during IVF and impact on mental health 11-17 years later.
Do patients present different adjustment trajectories during and after IVF treatment? Most women show resilient trajectories during and after IVF treatment but 37% show temporary or chronic maladjustment during IVF and 10% are maladjusted 11-17 years after treatment. Research on patient psychosocial adjustment during treatment has contributed to identifying the most distressful stages of IVF treatment and profiling patients at risk for emotional maladjustment at these specific stages. This knowledge is currently driving the deliverance of psychosocial care at fertility clinics by tailoring it to patients' risk profiles and specific treatment stages. However, current care does not take into consideration how individuals adjust across the entire treatment pathway. This can be assessed by profiling individual adjustment trajectories. A longitudinal cohort study with five assessment moments that combines data from two different studies, the STRESSIVF and OMEGA projects. Participants enrolled in the STRESSIVF study (started IVF in 1998-2000) were assessed before and after the first IVF treatment cycle and 6 months and 2.5 years after the last IVF cycle. A subset participated in the OMEGA project (started IVF in 1995-2000) and reported on their mental health 11-17 years after treatment. Three hundred and forty-eight women participated in the STRESSIVF project and 108 of these in the OMEGA. Anxiety was measured with the State and Trait Anxiety Inventory, depression with the Beck Depression Inventory and mental health with the Mental Health Inventory. Latent class growth mixed modelling was carried out to identify distinct anxiety and depression trajectories over the four STRESSIVF study assessment moments. Multinominal logistic regressions were conducted to investigate predictors of trajectory membership, and stepwise linear regressions were performed to investigate if adjustment trajectories predicted mental health 11-17 years after IVF treatment. A total of 67 and 86% of women showed normal levels of anxiety and depression, respectively, throughout treatment (resilient trajectories), 24 and 33% experienced anxiety and depression only during treatment (recovery trajectories), 4.6 and 4.9% experienced anxiety and depression only after treatment (delayed trajectories), and 4.3% showed chronic anxiety (chronic trajectory, not identified for depression). Non-resilient trajectories were associated with unsuccessful treatment, marital dissatisfaction, lack of social support and negative infertility cognitions. One in 10 women had a delayed or chronic trajectory and these trajectories predicted serious mental health impairment 11-17 years after treatment. The study only focuses on women. In the OMEGA project adjustment was assessed using a mental health measure. Although we could investigate how trajectories predicted mental health, it would have been preferable to map anxiety and depression trajectories up to 11-17 years after treatment. Missing analysis showed selective dropout from the study but this was accounted for by using mixed models and imputation procedures. Finally, data on other life stressors were not collected; therefore any contribution from these events cannot be assessed. Fertility health-care providers have been called upon considering their responsibility in supporting patients in the aftermath of treatment. Results show it is possible to profile different groups of at-risk women at the start of the treatment and tailor psychosocial support to risk profile to promote health adjustment during treatment and thereafter. This study was supported by a grant from the Dutch Cancer Society (2006-3631) and the Praeventiefonds (28-3012). No competing interests exist.


Role of biomarkers in the diagnosis and management of cardio-renal syndromes.
The complex interaction between heart and kidney disease has been increasingly recognized over the recent years. Pathologies within these two organs frequently coexist and, due to organ cross-talk, dysfunction in one often leads to problems in the other. The classification of the various forms of cardio-renal syndrome has made these interactions clearer. To aid in the diagnosis, management and prognosis of these conditions, many novel cardiac and renal biomarkers have emerged to supplement traditional markers which have limited specificity and sensitivity. In this review we will summarize the literature on novel renal behind these and other biomarkers and discuss their potential relevance to the clinical scenarios of cardio-renal syndrome.


Effects of immediate postexercise carbohydrate ingestion with and without protein on neutrophil degranulation.
The purpose of the study was to determine the effects of carbohydrate (CHO) intake, with and without protein (PRO), immediately after prolonged strenuous exercise on circulating bacterially stimulated neutrophil degranulation. Twelve male runners completed 3 feeding interventions, 1 week apart, in randomized order after 2 hr of running at 75% VO2max. The feeding interventions included a placebo solution, a CHO solution equal to 1.2 g CHO/kg body mass (BM), and a CHO-PRO solution equal to 1.2 g CHO/kg BM and 0.4 g PRO/kg BM (CHO+PRO) immediately postexercise. All solutions were flavor and water-volume equivalent (12 ml/kg BM). Circulating leukocyte counts, bacterially stimulated neutrophil degranulation, plasma insulin, and cortisol were determined from blood samples collected preexercise, immediately postexercise, and every 30 min until 180 min postexercise. The immediate postexercise circulating leukocytosis, neutrophilia, and lymphocytosis (p < .01 vs. preexercise) and the delayed lymphopenia (90 min postexercise, p < .05 vs. preexercise) were similar on all trials. Bacterially stimulated neutrophil degranulation decreased during recovery in control (23% at 180 min, p < .01 vs. preexercise) but remained above preexercise levels with CHO and CHO+PRO. In conclusion, CHO ingestion, with or without PRO, immediately after prolonged strenuous exercise prevented the decrease in bacterially stimulated neutrophil degranulation during recovery.


A normobaric hypoxia facility for preparing polycythemic mice for assay of erythropoietin.
A normobaric hypoxia chamber was designed in which large numbers of mice (up to 250) were made polycythemic, after which they were used in an erythropoietin assay. The hypoxic atmosphere was composed of air diluted with N2 gas generated from liquid N2. Continuous exposure of mice to 8% O2 for 11 da resulted in a polycythemia of sufficient magnitude and duration to provide appropriate erythropoietic conditions for the erythropoietin assay. The chamber, which has been in almost continuous operation for 3 yr, requires little attention and maintenance and has proved to be reliable, safe, and economical.


The bulk crystallization of alpha-lactose monohydrate from aqueous solution.
The bulk crystallization of alpha-lactose monohydrate from aqueous solution by primary nucleation has been studied under controlled conditions of supersaturation, temperature, and pH. The induction times to nucleation were extremely long compared with those generally observed for other materials, even at the high supersaturations used in the experiment. As a result, it was necessary to stir the supersaturated solution vigorously to induce nucleation in a reasonable but still lengthy working time. Even then, nucleation only occurred to a limited extent, following which growth ceased for 8-10 h before resuming. After this period, growth recommenced but again slowed to a low rate after another 8 h. At this stage, the yield of product was low and in most cases the particles had achieved sizes close to the maximum noted. The yields increased with further crystallization time (22-72 h total from the recommencement of growth) to give, under high initial supersaturation conditions, amounts of product close to the theoretical value. For the most part, however, the particle size did not increase with this later increase in yield, showing only significant changes after the extremely long total crystallization times. It is proposed that these extreme properties result from the formation in solution by mutarotation of the anomer alpha-lactose, which inhibits nucleation as well as its previously observed influence on growth.


Cultivating the Interpersonal Domain: Compassion in the Supervisor-Doctoral Student Relationship.
The long-term and complex supervisor-doctoral student relationship is often characterised by tension and frictions. In higher education research, models, and interventions that take the potential beneficial interpersonal effects of compassion into account seem to be scarce. Hence, the aim of this study was to conceptualise the potential role compassion could have in the cultivation of an affiliative and sustainable supervisor-doctoral student relationship. The concept of compassion was investigated and analysed in relation to a contemporary model of supervisor behaviours. Furthermore, a systematic literature search in the scientific databases PubMed, PsychInfo, ScienceDirect, and Google Scholar was performed. The conceptual analysis revealed that the interpersonal domain, in which compassion could afford a shared sense of warmth, is neglected in previous definitions. Furthermore, the integration of compassion into a model of adaptive supervisor behaviour indicates a strong case for a salutary role for compassion in the supervisor-doctoral student relationship. However, the literature review showed that empirical data are lacking, and more studies are needed. The role of compassion deserves to be investigated empirically in this particular interpersonal context.


Vaspin in the pig ovarian follicles: expression and regulation by different hormones.
Vaspin, also known as visceral adipose tissue-derived serine protease inhibitor, is a member of the serine protease inhibitor family. Its expression is associated with obesity, insulin resistance and type 2 diabetes, and elevated concentration is observed in polycystic ovary syndrome. However, vaspin has never been studied in the ovary. Here, we identified vaspin in two prolific breeds of pigs: fat Meishan (MS) and lean Large White (LW). We then investigated the molecular mechanism involved in the regulation of its expression in response to gonadotropins, insulin, insulin-like growth factor type 1 (IGF-1) and steroids (progesterone, testosterone and oestradiol) in ovarian follicles cells. Using real-time PCR and Western blot, we found higher vaspin mRNA and protein expression in the ovarian follicles and adipose tissue at 10-12 days of the oestrous cycle in MS compared to LW. Moreover, vaspin expression, as well as its concentration in plasma and follicular fluid, decreased in ovarian follicles of LW during days of the oestrous cycle, while the opposite results were noted in MS. Immunohistochemistry showed vaspin in granulosa, theca, cumulus cells and oocytes as well as in adipocytes. Vaspin level in the ovary increased by gonadotropin, insulin, IGF-1 and steroids stimulation through kinases JAK/Stat, ERK1/2, PI3K and AMPK, as well as factor NF-κB. These findings all show vaspin expression and regulation in the pig ovary, indicating vaspin as a new regulator in female reproduction. Future studies will be necessary for understanding the role of vaspin on ovarian physiology providing new insights into the pathology of ovaries.


Targeting BRF2: insights from in silico screening and molecular dynamic simulations.
The Transcription factor II B (TFIIB)‑related factor 2 (BRF2) containing TFIIIB complex recruits RNA polymerase III multi-subunit complex to selective gene promoters that altogether are responsible for synthesizing a variety of small non-coding RNAs, including a special type of selenocysteine tRNA (tRNASec), micro-RNA (miRNA), and other regulatory RNAs. BRF2 has been identified as a potential oncogene that promotes cancer cell survival under oxidative stress through its genetic activation. The structure of the BRF2 protein was modeled using the Robetta server, refined, and validated using the Ramachandran plot. A virtual approach utilizing molecular docking was used to screen a natural compound library to determine potential compounds that can interact with the molecular pin motif of the BRF2 protein using Maestro (Schrodinger). Subsequent molecular dynamics simulation studies of the top four ligands that exhibited low glide scores were performed using GROMACS. The findings derived from the simulations, in conjunction with the exploration of hydrogen bonding patterns, evaluation of the free energy landscape, and thorough analysis of residue decomposition, collectively converged to emphasize the robust interaction characteristics exhibited by Ligand 366 (Deacetyl lanatoside C) and ligand 336 (Neogitogenin)-with the BRF2 protein. These natural compounds may be potential inhibitors of BRF2, which could modulate the regulation of selenoprotein synthesis in cancer cells. Targeting BRF2 using these promising compounds may offer a new therapeutic approach to sensitize cancer cells to ferroptosis and apoptosis.Communicated by Ramaswamy H. Sarma.


No difference in compensation for sugar in a drink versus sugar in semi-solid and solid foods.
It is claimed that sugar consumed in a drink is poorly compensated for by a reduction in subsequent energy intake, however very little research has tested directly the effect on appetite of adding sugar to a drink versus food. In this between subjects study, 144 participants (72 men) consumed preloads sweetened with either sucrose or the low-energy sweetener, sucralose (preload energy difference 162kcal) in the form of a blackcurrant drink, jelly or candy. The different preload viscosities were achieved by varying the amount of thickener (carrageenan) and water in the recipes. Participants completed hunger ratings before and 5, 10 and 20min after consuming their preload. After the 20-minute rating they were served a test-meal comprising an excess of bite-sized sandwiches and a sweet dessert. Energy intake measured for the same meal consumed the previous day (baseline day, no preload consumed) was used in the data analyses to control for individual differences in energy intake. Overall, there was 36% compensation for the energy difference in the preloads, but this did not vary with preload viscosity - if anything compensation was greater for the drink preload, and greater in men. The drink preload also showed an effect of sucrose versus sucralose for hunger. The lack of the predicted effect of viscosity on compensation could not be explained by differences in blood-glucose concentration 20min after the preload (measured in a separate study) or by differences in preload sweetness, flavour intensity, liking or familiarity. Comparison of baseline and test-meal food intakes indicated that, irrespective of energy content, the sweet drinks reduced the relative intake of sweet food. In conclusion, short-term energy compensation did not differ across a set of realistic drink and food stimuli.


Context-dependent seed dispersal by a scatter-hoarding corvid.
Corvids (crows, jays, magpies and nutcrackers) are important dispersers of large-seeded plants. Studies on captive or supplemented birds suggest that they flexibly adjust their scatter-hoarding behaviour to the context of social dynamics and relative seed availability. Because many corvid-dispersed trees show high annual variation in seed production, context-dependent foraging can have strong effects on natural corvid scatter-hoarding behaviour. We investigated how seed availability and social dynamics affected scatter-hoarding in the island scrub jays (Aphelocoma insularis). We quantified rates of scatter-hoarding behaviour and territorial defence of 26 colour-marked birds over a three-year period with variable acorn crops. We tested whether caching parameters were correlated with variation in annual seed production of oaks as predicted by the predator dispersal hypothesis, which states that caching rates and distances should vary with seed abundance in ways that benefit tree fitness. We also tested whether antagonistic interactions with conspecifics would affect scatter-hoarding adversely, as found in experimental studies. Caching behaviour varied with acorn availability. Caching distances correlated positively with annual acorn crop size, increasing by as much as 40% between years. Caching rates declined over time in years with small acorn crops, but increased when crops were large. Acorn foraging and caching rates were also negatively correlated with rates of territorial aggression. Overall foraging rates, however, were not associated with aggression, suggesting that reduced dispersal rates were not simply due to time constraints. Our field results support laboratory findings that caching rates and distances by scatter-hoarding corvids are context-dependent. Furthermore, our results are consistent with predictions of the predator dispersal hypothesis and suggest that large seed crops and social interactions among scatter-hoarders affect dispersal benefits for oaks and other masting tree species.


Four-State Model for Simulating Kinetic and Steady-State Voltage-Dependent Gating of Gap Junctions.
Gap junction (GJ) channels, formed of connexin (Cx) proteins, provide a direct pathway for metabolic and electrical cell-to-cell communication. These specialized channels are not just passive conduits for the passage of ions and metabolites but have been shown to gate robustly in response to transjunctional voltage, Vj, the voltage difference between two coupled cells. Voltage gating of GJs could play a physiological role, particularly in excitable cells, which can generate large transients in membrane potential during the propagation of action potentials. We present a mathematical/computational model of GJ channel voltage gating to assess properties of GJ channels that takes into account contingent gating of two series hemichannels and the distribution of Vj across each hemichannel. From electrophysiological recordings in cell cultures expressing Cx43 or Cx45, the principal isoforms expressed in cardiac tissue, various data sets were fitted simultaneously using global optimization. The results showed that the model is capable of describing both steady-state and kinetic properties of homotypic and heterotypic GJ channels composed of these Cxs. Moreover, mathematical analyses showed that the model can be simplified to a reversible two-state system and solved analytically using a rapid equilibrium assumption. Given that excitable cells are arranged in interconnected networks, the equilibrium assumption allows for a substantial reduction in computation time, which is useful in simulations of large clusters of coupled cells. Overall, this model can serve as a tool for the studying of GJ channel gating and its effects on the spread of excitation in networks of electrically coupled cells.


Computational feasibility of simulating whole-organ vascular networks.
The human body contains approximately 20 billion blood vessels, which transport nutrients, oxygen, immune cells, and signals throughout the body. The brain's vasculature includes up to 9 billion of these vessels to support cognition, motor processes, and myriad other vital functions. To model blood flowing through a vasculature, a geometric description of the vessels is required. Previously reported attempts to model vascular geometries have produced highly-detailed models. These models, however, are limited to a small fraction of the human brain, and little was known about the feasibility of computationally modeling whole-organ-sized networks. We implemented a fractal-based algorithm to construct a vasculature the size of the human brain and evaluated the algorithm's speed and memory requirements. Using high-performance computing systems, the algorithm constructed a vasculature comprising 17 billion vessels in 1960 core-hours, or 49 minutes of wall-clock time, and required less than 32 GB of memory per node. We demonstrated strong scalability that was limited mainly by input/output operations. The results of this study demonstrated, for the first time, that it is feasible to computationally model the vasculature of the whole human brain. These findings provide key insights into the computational aspects of modeling whole-organ vasculature.


Informal Caregivers' Perspectives on the Mandated No Visitation Policy During COVID-19 Pandemic in Long-Term Care: A Qualitative Study.
The current descriptive qualitative study aimed to explore how informal caregivers of persons residing in long-term care (LTC) facilities are coping with the no visitation policy during the coronavirus disease 2019 (COVID-19) pandemic. Semi-structured interviews were conducted approximately 1 month after the no visitation policy was implemented. Interview questions explored how informal caregivers are feeling, coping, and staying connected and involved with loved ones residing in LTC. Recruitment (N = 14) occurred through social media, email, and word of mouth. To maintain social distance and reduce transmission risk, interviews were conducted by phone. Through systematic data reduction, six themes emerged: (a) Reminiscing About Life Before COVID-19, (b) Feelings Related to Physical Separation, (c) Our Loved Ones Are Lonely and Don't Understand, (d) Creating Ways to Stay Connected, (e) Recognition and Concern for LTC Staff, and (f) Coping During Future No Visitation Mandates. Results of this study may assist LTC administrators and nurses if no visitation policies are required in the future. [Journal of Gerontological Nursing, 47(12), 19-26.].


Slit2 Promotes Angiogenic Activity Via the Robo1-VEGFR2-ERK1/2 Pathway in Both In Vivo and In Vitro Studies.
Recent research has provided novel but contrary insight into the function of Slit2-Robo signaling in angiogenesis. Although the role of Robo in choroidal neovascularization (CNV) has been studied, the effect of its ligand, Slit2, on CNV development is unclear. This study investigated the role of endogenous Slit2 in CNV and the possible mechanisms. Laser-induced CNV in Slit2 transgenic and wild-type mice was used to study the effects of endogenous Slit2 on angiogenesis in vivo. Fluorescein angiography was performed to evaluate the leakage area of each lesion. Plasmid-based gene transfer technology was used to increase Slit2 expression and to study its effects on human umbilical vein endothelial cells (HUVECs) in vitro. Cell proliferation, migration, and tube formation were assessed. Quantitative real-time PCR and Western blot were used to measure expression in the extracellular signal-related kinase 1/2 (ERK1/2), protein kinase B (AKT), and p38 mitogen-activated protein kinase (p38 MAPK) molecular pathways. Laser treatment led to more CNV and vascular leakage in Slit2 transgenic mice compared with wild-type mice. Upregulation of Slit2, Robo1, VEGF receptor 2 (VEGFR2), and phosphorylated ERK1/2 (p-ERK1/2) were detected in retina and choroidal tissue of laser-treated transgenic mice. After transfection of HUVECs with a Slit2 overexpression plasmid, cell proliferation, migration, and tube formation capacities were promoted. Slit2, Robo1, VEGFR2, and p-ERK1/2 were elevated in transfected HUVECs. Slit2 overexpression promoted angiogenic effects in both a laser-induced CNV mouse model and HUVECs and promoted the biological activity of endothelial cells. Slit2 may promote angiogenesis by upregulating Robo1 and activating the VEGFR2-ERK1/2 pathway.


Growth mechanism of a preferentially oriented mordenite membrane.
A preferentially oriented mordenite membrane was successfully prepared on a seeded porous a-alumina support. Characterization results of XRD (X-ray diffractometer) and FE-SEM (field emission scanning electron microscope) revealed that evolutionary selection might predominantly contribute to the formation of the sharply oriented mordenite membrane. The necessary conditions under which evolutionary selection occurs are: (a) the number density of nuclei on the support surface should be high enough at the early stage; (b) the crystals should grow fastest along one direction; and (c) the zeolite layer should proceed via the successive growth of the crystals nucleated on the support surface instead of the accumulation of the crystals formed in the bulk solution.


Psychological Discomfort in Nursing Degree Students as a Consequence of the COVID-19 Pandemic.
Students are a population at risk of developing psychological complications, such as psychological discomfort, stress, and anxiety, among other problems, especially during the current health crisis due to the COVID-19 pandemic. The present study's objective was to analyze the effects of the COVID-19 pandemic on the psychological discomfort of final-year nursing students. A cross-sectional descriptive observational study was carried out. To analyze the psychological discomfort of the participants, the Kessler test (previously validated) was used. The results of this test were divided into two levels (High ≥ 21/Low < 21), showing high sensitivity as a screening method for anxiety and depression. Questionnaires were sent via email to final-year nursing students of Spanish and South American universities, inviting them to participate voluntarily. The sample consisted of 400 students, with an average age of 23.29 years and a sex proportion of 82.75% women and 17.28% men. Almost all participants (n = 396) belonged to Spanish universities, and the greatest participation corresponded to Andalusian universities (64.5%). The average psychological discomfort was high (M = 27.94). Statistically significant relationships were detected between age, sex, and feeling ready for the world of work, observing no relationships with the rest of the studied variables. The sample of 4th-year students of the Degree of Nursing presented a high level of psychological discomfort. This pathology does not seem to be related to having suffered from COVID-19 or being in contact with infected people during the practicum and is more strongly related to personal sociodemographic variables and students' preparation for the world of work.


Outcomes of steroid-avoidance protocols in pediatric kidney transplant recipients.
Advances in immunosuppression have facilitated increased use of steroid-avoidance protocols in pediatric kidney transplantation. To evaluate such steroid avoidance, a retrospective cohort analysis of pediatric kidney transplant recipients between 2002 and 2009 in the United Network for Organ Sharing database was performed. Outcomes (acute rejection and graft loss) in steroid-based and steroid-avoidance protocols were assessed in 4627 children who received tacrolimus and mycophenolate immunosuppression and did not have multiorgan transplants. Compared to steroid-based protocols, steroid avoidance was associated with decreased risk of acute rejection at 6 months posttransplant (8.3% vs. 10.9%, p = 0.02) and improved 5-year graft survival (84% vs. 78%, p < 0.001). However, patients not receiving steroids experienced less delayed graft function (p = 0.01) and pretransplant dialysis, were less likely to be African-American and more frequently received a first transplant from a living donor (all p < 0.001). In multivariate analysis, steroid avoidance trended toward decreased acute rejection at 6 months, but this no longer reached statistical significance, and there was no association of steroid avoidance with graft loss. We conclude that, in clinical practice, steroid avoidance appears safe with regard to graft rejection and loss in pediatric kidney transplant recipients at lower immunologic risk.


Acetyl-Click Screening Platform Identifies Small-Molecule Inhibitors of Histone Acetyltransferase 1 (HAT1).
HAT1 is a central regulator of chromatin synthesis that acetylates nascent histone H4. To ascertain whether targeting HAT1 is a viable anticancer treatment strategy, we sought to identify small-molecule inhibitors of HAT1 by developing a high-throughput HAT1 acetyl-click assay. Screening of small-molecule libraries led to the discovery of multiple riboflavin analogs that inhibited HAT1 enzymatic activity. Compounds were refined by synthesis and testing of over 70 analogs, which yielded structure-activity relationships. The isoalloxazine core was required for enzymatic inhibition, whereas modifications of the ribityl side chain improved enzymatic potency and cellular growth suppression. One compound (JG-2016 [24a]) showed relative specificity toward HAT1 compared to other acetyltransferases, suppressed the growth of human cancer cell lines, impaired enzymatic activity in cellulo, and interfered with tumor growth. This is the first report of a small-molecule inhibitor of the HAT1 enzyme complex and represents a step toward targeting this pathway for cancer therapy.


UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota.
The composition of the human microbiota is recognized as an important factor in human health and disease. Many of our cohabitating microbes belong to phylum-level divisions for which there are no cultivated representatives and are only represented by small subunit rRNA sequences. For one such taxon (SR1), which includes bacteria with elevated abundance in periodontitis, we provide a single-cell genome sequence from a healthy oral sample. SR1 bacteria use a unique genetic code. In-frame TGA (opal) codons are found in most genes (85%), often at loci normally encoding conserved glycine residues. UGA appears not to function as a stop codon and is in equilibrium with the canonical GGN glycine codons, displaying strain-specific variation across the human population. SR1 encodes a divergent tRNA(Gly)UCA with an opal-decoding anticodon. SR1 glycyl-tRNA synthetase acylates tRNA(Gly)UCA with glycine in vitro with similar activity compared with normal tRNA(Gly)UCC. Coexpression of SR1 glycyl-tRNA synthetase and tRNA(Gly)UCA in Escherichia coli yields significant β-galactosidase activity in vivo from a lacZ gene containing an in-frame TGA codon. Comparative genomic analysis with Human Microbiome Project data revealed that the human body harbors a striking diversity of SR1 bacteria. This is a surprising finding because SR1 is most closely related to bacteria that live in anoxic and thermal environments. Some of these bacteria share common genetic and metabolic features with SR1, including UGA to glycine reassignment and an archaeal-type ribulose-1,5-bisphosphate carboxylase (RubisCO) involved in AMP recycling. UGA codon reassignment renders SR1 genes untranslatable by other bacteria, which impacts horizontal gene transfer within the human microbiota.


Determination of absorbed dose to water in reference conditions for radiotherapy kilovoltage x-rays between 10 and 300 kV: a comparison of the data in the IAEA, IPEMB, DIN and NCS dosimetry protocols.
A comparison of four of the most commonly used dosimetry protocols for the determination of absorbed dose to water in therapeutic kilovoltage x-rays using an ionization chamber (IAEA TRS-277, IPEMB, DIN and NCS) has been carried out. Owing to the different energy ranges and HVLs recommended by each protocol, backscatter factors, water-to-air mass energy absorption coefficient ratios and perturbation correction factors have been recast to a common quality range that all protocols satisfy individually to make a comparison possible. The results of the comparison show that in the sometimes reduced quality range originally included by the different protocols, determinations of absorbed dose to water at all beam qualities agree to within +/-1.0% with that obtained using the second edition of the IAEA TRS-277 code of practice (1997). The extrapolation of data to a common beam quality range practically preserves the agreement for all the protocols except for that issued by the NCS at the extremes of the range, where differences of up to 1.8% and 1.4% have been found for low and medium energies respectively. In all cases the DIN protocol yields very good agreement with TRS-277.


Colorimetric detection of urine glucose using a C/CdTe QDs-GOx aerogel based on a microfluidic assay sensor.
A sensitive fluorescent microfluidic sensor based on carbon quantum dots (CQDs), cadmium telluride quantum dots (CdTe QDs) aerogel and glucose oxidase (GOx) for urinal glucose detection was fabricated via a simple method. CQDs, emitting green fluorescence (emission peak at 520 nm) and the CdTe QDs, emitting red fluorescence (emission peak at 620 nm) under 365 nm ultraviolet irradiation, were synthesized. The as-prepared CQDs, CdTe QDs and GOx (C/CdTe QD-GOx) were mixed in a certain ratio and were then introduced into the microfluidic chip to construct a three-dimensional porous aerogel sensor after freeze-drying. A ratiometric fluorescence response was realized through the quenching of the red fluorescence by H2O2 produced from the glucose/GOx reaction, while the green fluorescence intensity stays constant. A small change in the ratio of the two fluorescence intensities led to a clear change in the fluorescent colour of the sensor, which can be easily observed under a UV lamp. The microsensor displayed a serial colour change from red to green with the changes in glucose concentration. The intensity ratio between the red fluorescence and green fluorescence (R/G value) indicates the glucose concentration. In our experiments, the optimal concentration ratio of CdTe QDs and CQDs was 0.5 : 1, and the optimal response time was 5 min. The detection range of glucose concentration was from 0 mM to 13 mM, and the detection limit was 0.223 mM. We also found that this glucose sensor has excellent selectivity, specificity and stability. The as-prepared microsensor can be stably stored for 30 days under -20 °C. Such a C/CdTe QD-GOx aerogel based microfluidic assay sensor provides a new approach towards the optical and quantitative detection of glucose, which enables daily urine glucose monitoring for the diabetic patients in a convenient way.


Quality of antenatal care in rural Tanzania: counselling on pregnancy danger signs.
The high rate of antenatal care attendance in sub-Saharan Africa, should facilitate provision of information on signs of potential pregnancy complications. The aim of this study was to assess quality of antenatal care with respect to providers' counselling of pregnancy danger signs in Rufiji district, Tanzania. A cross-sectional study was conducted in 18 primary health facilities. Thirty two providers were observed providing antenatal care to 438 pregnant women. Information on counselling on pregnancy danger signs was collected by an observer. Exit interviews were conducted to 435 women. One hundred and eighty five (42%) clients were not informed of any pregnancy danger signs. The most common pregnancy danger sign informed on was vaginal bleeding 50% followed by severe headache/blurred vision 45%. Nurse auxiliaries were three times more likely to inform a client of a danger sign than registered/enrolled nurses (OR = 3.7; 95% CI: 2.1-6.5) and Maternal Child Health Aides (OR = 2.3: 95% CI: 1.3-4.3) and public health nurses (OR = 2.5; CI: 1.4-4.2) were two times more likely to provide information on danger signs than registered/enrolled nurses. The clients recalled less than half of the pregnancy danger signs they had been informed during the interaction. Two out of five clients were not counselled on pregnancy danger signs. The higher trained cadre, registered/enrolled nurses were not informing majority of clients pregnancy danger signs compared to the lower cadres. Supportive supervision should be made to enhance counselling of pregnancy danger signs. Nurse auxiliaries should be encouraged and given chance for further training and upgrading to improve their performance and increase human resource for health.


Identification of gastric signet ring cell carcinoma based on endoscopic images using few-shot learning.
Deep learning (DL) models perform poorly when there are limited gastric signet ring cell carcinoma (SRCC) samples. Few-shot learning (FSL) can address the small sample problem. EfficientNetV2-S was first pretrained on ImageNet and then pretrained on esophageal endoscopic images (i.e., base classes: normal vs. early cancer vs. advanced cancer) using transfer learning. Second, images of gastric benign ulcers, adenocarcinoma and SRCC, i.e., novel classes (n = 50 per class), were included. Image features were extracted as vectors using the dual pretrained EfficientNetV2-S. Finally, a k-nearest neighbor classifier was used to identify SRCC. The above proposed 3-way 3-shot FSL framework was conducted in three rounds. Dual pretrained FSL performed better than single pretrained FSL, endoscopists and traditional EfficientNetV2-S models. Dual pretrained FSL obtained the highest accuracy (79.4%), sensitivity (68.8%), recall (68.8%), precision (69.3%) and F1-score (0.691), and the senior endoscopist achieved the highest specificity of 93.6% when identifying SRCC. The macro-AUC and F1-score for dual pretraining (0.763 and 0.703, respectively) were higher than those for single pretraining (0.656 and 0.537, respectively), along with endoscopists and traditional EfficientNetV2-S models. The 2-way 3-shot FSL also performed better. The proposed FSL framework showed practical performance in the differentiation of SRCC on endoscopic images, suggesting the potential of FSL in the computer-aided diagnosis for rare diseases.


Tumor evasion of the immune system: inhibiting p38 MAPK signaling restores the function of dendritic cells in multiple myeloma.
Dendritic cells (DCs) from patients with cancer are functionally defective, but the molecular mechanisms underlying these defects are poorly understood. In this study, we used the murine 5TGM1 myeloma model to examine the effects and mechanisms of tumor-derived factors on the differentiation and function of DCs. Myeloma cells or tumor culture conditioning medium (TCCM) were shown to inhibit the differentiation and function of BM-derived DCs (BMDCs), as evidenced by the down-regulated expression of DC-related surface molecules, decreased IL-12, and compromised capacity of the cells to activate allospecific T cells. Moreover, TCCM-treated BMDCs were inferior to normal BMDCs at priming tumor-specific immune responses in vivo. Neutralizing antibodies against IL-6, IL-10, and TGF-beta partially abrogated the effects. TCCM treatment activated p38 mitogen-activated protein kinase (MAPK) and Janus kinase (JNK) but inhibited extracellular regulated kinase (ERK). Inhibiting p38 MAPK restored the phenotype, cytokine secretion, and function of TCCM-treated BMDCs. BMDCs from cultures with TCCM and p38 inhibitor was as efficacious as normal BMDCs at inducing tumor-specific antibody, type 1 T cell, and cytotoxic T lymphocyte (CTL) responses and at prolonging mouse survival. Thus, our results suggested that tumor-induced p38 MAPK activation and ERK inhibition in DCs may be a new mechanism for tumor evasion and that regulating these pathways during DC differentiation provides new strategies for generating potent DC vaccines for immunotherapy in patients with cancer.


Direct in vivo gene transfer into the coronary and peripheral vasculatures of the intact dog.
Gene therapy approaches have been suggested for the treatment of cardiovascular disease. Recently, direct transfer of the gene encoding beta-galactosidase into peripheral arteries of the pig has been demonstrated. To determine whether this approach is applicable to other arterial beds and to other species, we first evaluated the use of beta-galactosidase as a marker protein in the canine model. We demonstrate that variable but substantial endogenous beta-galactosidase-like activity is induced by manipulation of canine peripheral arteries, which precludes the use of this marker protein in evaluating the efficiency of gene transfer in this model. A marker gene encoding firefly luciferase was then evaluated, and background luciferase activity was found to be low in the dog even after arterial manipulation. Using the luciferase gene, we then demonstrated lipid-mediated gene transfer directly into both coronary and peripheral arteries of the intact dog. These results indicate the feasibility of in vivo gene transfer into coronary arteries and demonstrate the use of the luciferase marker protein in quantifying recombinant protein expression following gene transfer in canine models. This simple and effective method for direct in vivo gene transfer into coronary and peripheral arteries may be applicable to the localized production of therapeutically important proteins for the treatment of cardiovascular diseases.


Murine macrophage-based iNos reporter reveals polarization and reprogramming in the context of breast cancer.
As part of the first line of defense against pathogens, macrophages possess the ability to differentiate into divergent phenotypes with varying functions. The process by which these cells change their characteristics, commonly referred to as macrophage polarization, allows them to change into broadly pro-inflammatory (M1) or anti-inflammatory (M2) subtypes, and depends on the polarizing stimuli. Deregulation of macrophage phenotypes can result in different pathologies or affect the nature of some diseases, such as cancer and atherosclerosis. Therefore, a better understanding of macrophage phenotype conversion in relevant models is needed to elucidate its potential roles in disease. However, there are few existing probes to track macrophage changes in multicellular environments. In this study, we generated an eGFP reporter cell line based on inducible nitric oxide synthase (iNos) promoter activity in RAW264.7 cells (RAW:iNos-eGFP). iNos is associated with macrophage activation to pro-inflammatory states and decreases in immune-suppressing ones. We validated the fidelity of the reporter for iNos following cytokine-mediated polarization and confirmed that reporter and parental cells behaved similarly. RAW:iNos-eGFP cells were then used to track macrophage responses in different in vitro breast cancer models, and their re-education from anti- to pro-inflammatory phenotypes via a previously reported pyrimido(5,4-b)indole small molecule, PBI1. Using two mouse mammary carcinoma cell lines, 4T1 and EMT6, effects on macrophages were assessed via conditioned media, two-dimensional/monolayer co-culture, and three-dimensional spheroid models. While conditioned media derived from 4T1 or EMT6 cells and monolayer co-cultures of each cancer cell line with RAW:iNos-eGFP cells all resulted in decreased fluorescence, the trends and extents of effects differed. We also observed decreases in iNos-eGFP signal in the macrophages in co-culture assays with 4T1- or EMT6-based spheroids. We then showed that iNos production is enhanced in these cancer models using PBI1, tracking increased fluorescence. Collectively, this work demonstrates that this reporter-based approach provides a facile means to study macrophage responses in complex, multicomponent environments. Beyond the initial studies presented here, this platform can be used with a variety of in vitro models and extended to in vivo applications with intravital imaging.


Trans-Allelic Model for Prediction of Peptide:MHC-II Interactions.
Major histocompatibility complex class two (MHC-II) molecules are trans-membrane proteins and key components of the cellular immune system. Upon recognition of foreign peptides expressed on the MHC-II binding groove, CD4+ T cells mount an immune response against invading pathogens. Therefore, mechanistic identification and knowledge of physicochemical features that govern interactions between peptides and MHC-II molecules is useful for the design of effective epitope-based vaccines, as well as for understanding of immune responses. In this article, we present a comprehensive trans-allelic prediction model, a generalized version of our previous biophysical model, that can predict peptide interactions for all three human MHC-II loci (HLA-DR, HLA-DP, and HLA-DQ), using both peptide sequence data and structural information of MHC-II molecules. The advantage of this approach over other machine learning models is that it offers a simple and plausible physical explanation for peptide-MHC-II interactions. We train the model using a benchmark experimental dataset and measure its predictive performance using novel data. Despite its relative simplicity, we find that the model has comparable performance to the state-of-the-art method, the NetMHCIIpan method. Focusing on the physical basis of peptide-MHC binding, we find support for previous theoretical predictions about the contributions of certain binding pockets to the binding energy. In addition, we find that binding pocket P5 of HLA-DP, which was not previously considered as a primary anchor, does make strong contribution to the binding energy. Together, the results indicate that our model can serve as a useful complement to alternative approaches to predicting peptide-MHC interactions.


Radiological and clinical results of laminectomy and posterior stabilization for severe thoracolumbar burst fracture : surgical technique for one-stage operation.
This study aimed to show the possibility of neural canal enlargement and restoration of bony fragments through laminectomy and minimal facetectomy without pediculectomy or an anterior approach, and also to prove the adequacy of posterior stabilization of vertebral deformities after thoracolumbar bursting fracture. From January 2003 to June 2009, we experienced 45 patients with thoracolumbar burst fractures. All patients enrolled were presented with either a neural canal compromise of more than 40% with a Benzel-Larson Grade of VI, or more than 30% compromise with less than a Benzel-Larson Grade of V. Most important characteristic of our surgical procedure was repositioning retropulsed bone fragments using custom-designed instruments via laminectomy and minimal facetectomy without removing the fractured bone fragments. Beneath the dural sac, these custom-designed instruments could push the retropulsed bone fragments within the neural canal after the decompression and bone fragment repositioning. The mean kyphotic deformities measured preoperatively and at follow-up within 12 months were 17.7 degrees (±6.4 degrees) and 9.6 degrees (±5.2 degrees), respectively. The mean midsagittal diameter improved from 8.8 mm (±2.8 mm) before surgery to 14.2 mm (±1.6 mm) at follow-up. The mean traumatic vertebral body height before surgery was 41.3% (±12.6%). At follow-up assessment within 12 months, this score showed a statistically significant increase to 68.3% (±12.8%). Neurological improvement occurred in all patients. Though controversy exists in the treatment of severe thoracolumbar burst fracture, we achieved effective radiological and clinical results in the cases of burst fractures causing severe canal compromise and spinal deformity by using this novel custom-designed instruments, via posterior approach alone.


A comparison of cognitive structure in schizophrenia patients and healthy controls using confirmatory factor analysis.
There is evidence that cognitive task performance breaks down into the same broad domains in schizophrenia as in healthy populations. However, this does not mean that the domains are independent of one another or that the interrelationships among domains are the same between groups. We used confirmatory factor analysis (CFA) to compare the latent structure of a broad neuropsychological battery in schizophrenia patients (n = 148) and healthy controls (n = 157). Main analyses examined the fit of a hierarchical six-factor model, in which associations among the factors were assumed to reflect their strong shared relationship to a general cognitive ability factor. The model incorporated the factors of verbal comprehension, perceptual organization, verbal memory, spatial memory, processing speed, and executive/working memory. The hierarchical model provided a good overall fit to data from both groups. However multiple groups CFA revealed significant differences in factor loadings between groups, reflecting a more generalized latent structure of cognitive ability in schizophrenia. This was also evident in higher bivariate correlations among cognitive domain composite scores calculated from the observed test data. Cognitive ability, as reflected in test performance, appears to be more unitary in schizophrenia than in healthy subjects. This finding may have measurement and treatment implications.


Adverse Childhood Experiences as Predictors of Perceived Health: Assessing the ACE Pyramid Model Using Multiple-Mediation.
Adverse Childhood Experiences (ACEs) have been shown to contribute to a litany of mental and physical health problems, including several chronic diseases and death, via a model known as the ACE pyramid. Many of the results of ACEs in the ACE pyramid are known contributors to poor perceived health, which has significant health implications. Despite these results, a possible link between ACEs and perceived health has not been examined to date. Based on the temporal order of the ACE pyramid, we believe any relationship between ACEs and perceived health will be mediated by other components of the model. We conducted an analysis of the 2010 Behavioral Risk Factor Surveillance System (BRFSS) data for 4 states (Hawaii, Nevada, Vermont and Wisconsin).The Adverse Childhood Experiences Scale (11 questions) and Physical Health Days (days out of the last 30 where physical health was not good) were the primary predictor and outcome variables, respectively. The PHQ-8, a depression measure, served as a first-level mediator, while body mass index, Sleep Days (days out of the last 30 that sleep was poor) and average monthly alcohol consumption served as second-level mediators. We conducted a multiply-mediated regression using PROCESS (Hayes, 2018). The analysis included 6,060 respondents. ACEs were associated with an increase of 0.28 additional days of poor perceived health days per ACE through increases in depression and poor sleep. Adverse childhood experiences may influence perceived health through multiple intermediary factors, including depression and poor sleep quality. We discuss several theoretical and clinical implications, and future directions are proposed that take advantage of the multiply-mediated model.


Fornix white matter glia damage causes hippocampal gray matter damage during age-dependent limbic decline.
Aging leads to gray and white matter decline but their causation remains unclear. We explored two classes of models of age and dementia risk related brain changes. The first class of models emphasises the importance of gray matter: age and risk-related processes cause neurodegeneration and this causes damage in associated white matter tracts. The second class of models reverses the direction of causation: aging and risk factors cause white matter damage and this leads to gray matter damage. We compared these models with linear mediation analysis and quantitative MRI indices (from diffusion, quantitative magnetization transfer and relaxometry imaging) of tissue properties in two limbic structures implicated in age-related memory decline: the hippocampus and the fornix in 166 asymptomatic individuals (aged 38-71 years). Aging was associated with apparent glia but not neurite density damage in the fornix and the hippocampus. Mediation analysis supported white matter damage causing gray matter decline; controlling for fornix glia damage, the correlations between age and hippocampal damage disappear, but not vice versa. Fornix and hippocampal differences were both associated with reductions in episodic memory performance. These results suggest that fornix white matter glia damage may cause hippocampal gray matter damage during age-dependent limbic decline.


Wernicke's encephalopathy during parenteral nutrition.
Thiamine deficiency in humans affects the cardiovascular, muscular, nervous, and gastrointestinal systems. Wernicke's encephalopathy is described in alcoholism, in hyperemesis gravidarum, and in prolonged IV feeding without vitamin supplementation. We report a case of a 66-year-old man undergoing surgery for acute necrotic-hemorrhagic pancreatitis, who presented a Wernicke's syndrome during parenteral nutrition (PN). After surgery, he was treated with infusion of industrial 3-compartment bags, without vitamin supplementation. On the seventh postoperative day, nausea and vomiting began, and 5 days later the patient showed diplopia, ataxia, general muscular stiffness, reduction of osteotendinous reflexes, confusional state, and thrombocytopenia. The magnetic resonance scan evidenced pathologic changes in the medial thalamus, in the third and fourth ventricular floor, in the cerebellar vermis, and in the periaqueductal gray substance. All neurologic signs and platelet blood count gradually normalized after IV supplementation of thiamine, 100 mg daily. The magnetic resonance scan repeated 40 days after the first one was normal. Our report points out the risk of incorrect procedures in management of industrial 3-compartment bags. Moreover, we suggest that thrombocytopenia may be related to thiamine deficiency.


A report template for molecular genetic tests designed to improve communication between the clinician and laboratory.
Errors are most likely to occur during the pre- and postanalytic phases of the genetic testing process, which can contribute to underuse, overuse, and misuse of genetic tests. To mitigate these errors, we created a template for molecular genetic test reports that utilizes the combined features of synoptic reporting and narrative interpretation. A variation of the Delphi consensus process with an expert panel was used to create a draft report template, which was further informed by focus group discussions with primary care physicians. There was agreement that molecular genetic test reports should present information in groupings that flow in a logical manner, and most participants preferred the following order of presentation: patient and physician information, test performed, test results and interpretation, guidance on next steps, and supplemental information. We define data elements for the report as "required," "optional," "possible," and "not necessary"; provide recommendations regarding the grouping of these data elements; and describe the ideal design of the report template, including the preferred order of the report sections, formatting of data, and length of the report. With input from key stakeholders and building upon prior work, we created a template for molecular genetic test reports designed to improve clinical decision making at the point of care. The template design should lead to more effective communication between the laboratory and ordering clinician. Studies are needed to assess the usefulness and effectiveness of molecular genetic test reports generated using this template.


α-Actinin-4 Promotes the Progression of Prostate Cancer Through the Akt/GSK-3β/β-Catenin Signaling Pathway.
The first-line treatment for prostate cancer (PCa) is androgen ablation therapy. However, prostate tumors generally recur and progress to androgen-independent PCa (AIPC) within 2-3 years. α-Actinin-4 (ACTN4) is an actin-binding protein that belongs to the spectrin gene superfamily and acts as an oncogene in various cancer types. Although ACTN4 is involved in tumorigenesis and the epithelial-mesenchymal transition of cervical cancer, the role of ACTN4 in PCa remains unknown. We found that the ACTN4 expression level increased during the transition from androgen-dependent PCa to AIPC. ACTN4 overexpression resulted in enhanced proliferation and motility of PCa cells. Increased β-catenin due to ACTN4 promoted the transcription of genes involved in proliferation and metastasis such as CCND1 and ZEB1. ACTN4-overexpressing androgen-sensitive PCa cells were able to grow in charcoal-stripped media. In contrast, ACTN4 knockdown using si-ACTN4 and ACTN4 nanobody suppressed the proliferation, migration, and invasion of AIPC cells. Results of the xenograft experiment revealed that the mice injected with LNCaPACTN4 cells exhibited an increase in tumor mass compared with those injected with LNCaPMock cells. These results indicate that ACTN4 is involved in AIPC transition and promotes the progression of PCa.


Full 180° magnetization reversal with electric fields.
Achieving 180° magnetization reversal with an electric field rather than a current or magnetic field is a fundamental challenge and represents a technological breakthrough towards new memory cell designs. Here we propose a mesoscale morphological engineering approach to accomplishing full 180° magnetization reversals with electric fields by utilizing both the in-plane piezostrains and magnetic shape anisotropy of a multiferroic heterostructure. Using phase-field simulations, we examined a patterned single-domain nanomagnet with four-fold magnetic axis on a ferroelectric layer with electric-field-induced uniaxial strains. We demonstrated that the uniaxial piezostrains, if non-collinear to the magnetic easy axis of the nanomagnet at certain angles, induce two successive, deterministic 90° magnetization rotations, thereby leading to full 180° magnetization reversals.


Neural site of leptin influence on neuropeptide Y signaling pathways altering feeding and uncoupling protein.
Inhibition of a signal that produces positive energy balance involving neuropeptide Y (NPY) projection from arcuate nucleus (Arc; site of NPY synthesis) to paraventricular nucleus (PVN; site of NPY release) is one potential mechanism of leptin action. NPY in the PVN increases feeding and decreases uncoupling protein (UCP) activity in brown fat, whereas leptin decreases NPY biosynthesis in the Arc, which presumably decreases PVN NPY. It is hypothesized that decreased NPY activity is necessary for the satiety and thermogenic effects of leptin. To test this, we first determined the effect of leptin on feeding in two paradigms: satiated rats and food-deprived rats. Leptin was effective in decreasing feeding in the satiated rats but ineffective in the food-deprived rats. Next, we determined that leptin decreases NPY and increases UCP gene expression. Finally, we injected leptin intracerebroventricularly before specific PVN NPY microinjection. We found that repletion of NPY in PVN by specific NPY microinjection reverses the feeding-inhibitory and thermogenic effects of centrally administered leptin, the first functional evidence indicating that leptin acts on the Arc-PVN feeding-regulatory pathway.


Evidence of a Synergistic Effect between Pea Seed and Wheat Grain Endogenous Phytase Activities.
Distribution of phytic acid and phytase activity in pea seeds was analyzed and compared with those in wheat grains under identical assay conditions (55 °C, pH 5.5). Most total phytic acid content and phytase activity were found in pea cotyledons. In wheat grains, debranning resulted in a 70% reduction in phytic acid content, whereas more than 40% of the total phytase activity remained. The possibility to hydrolyze phytic acid by use of ground debranned wheat as a source of phytase in blends with pea cotyledon flour was investigated. The Michaelis-Menten parameters for each endogenous enzyme were identified and used to predict the rate of phytic acid hydrolysis. Results demonstrate a synergistic effect between the two phytase activities, enabling a 70-95% reduction of phytic acid depending on pea/wheat flour ratios in a relatively short time (4 h). This reduction appears to be able to increase zinc bioavailability but remains insufficient for iron.


Epidermolysis bullosa simplex and mottled pigmentation: a new dominant syndrome. I. Clinical and histological features.
A family is reported in which 11 members presented epidermolysis bullosa simplex with some unusual features, and 10 of whom had congenital mottled hyper- and hypopigmentation of the skin. Both anomalies are inherited together in an autosomal dominant fashion, although dominant X-linkage cannot be excluded. The epidermolysis without dyspigmentation in the 11th individual suggests that the syndrome in the other 10 members is due to genetic linkage of two independent genes and not to pleiotropism of a single mutant gene. The mottled pigmentation seems distinct from previously known dyspigmentations and is also suggestive of autosomal inactivation in man. (See addendum).


Hyponatraemia in Emergency Medical Admissions-Outcomes and Costs.
Healthcare systems in the developed world are struggling with the demand of emergency room presentations; the study of the factors driving such demand is of fundamental importance. From a database of all emergency medical admissions (66,933 episodes in 36,271 patients) to St James' Hospital, Dublin, Ireland, over 12 years (2002 to 2013) we have explored the impact of hyponatraemia on outcomes (30 days in-hospital mortality, length of stay (LOS) and costs). Identified variables, including Acute Illness Severity, Charlson Co-Morbidity and Chronic Disabling Disease that proved predictive univariately were entered into a multivariable logistic regression model to predict the bivariate of 30 days in-hospital survival. A zero truncated Poisson regression model assessed LOS and episode costs and the incidence rate ratios were calculated. Hyponatraemia was present in 22.7% of episodes and 20.3% of patients. The 30 days in-hospital mortality rate for hyponatraemic patients was higher (15.9% vs. 6.9% p < 0.001) and the LOS longer (6.3 (95% CI 2.9, 12.2) vs. 4.0 (95% CI 1.5, 8.2) p < 0.001). Both parameters worsened with the severity of the initial sodium level. Hospital costs increased non-linearly with the severity of initial hyponatraemia. Hyponatraemia remained an independent predictor of 30 days in-hospital mortality, length of stay and costs in the multi-variable model.


Inactivation of poliovirus type 1 by the Kelly-Purdy ultraviolet seawater treatment unit.
Three experiments were conducted to determine the effect of ultraviolet (UV) radiation on poliovirus-contaminated seawater. In two of the experiments, the effectiveness of the Kelly-Purdy UV Seawater Treatment Unit to inactivate poliovirus type 1 (T(1)) suspended in continuously flowing seawater was determined. In experiment 1, the observed survival ratio of poliovirus T(1) was 2.3 x 10(-4) (99.98% reduction) in 15.7 sec. No virus was detected (<0.2 plaque-forming unit/ml) in 20.6 seconds. The calculated half-life value was 1.29 sec. In experiment 2, the observed survival ratio of poliovirus T(1) was 5.9 x 10(-4) (99.94% reduction) in 11.7 sec. No virus was detected in 15.7 sec. The calculated half-life value was 1.37 sec. In experiment 3, a laboratory-controlled UV experiment designed to closely simulate the geometry of the continuously flowing seawater system, the observed survival ratios of poliovirus T(1) were 9.7 x 10(-3) (99.03% reduction) and 3.6 x 10(-4) (99.96% reduction) in 15 and 30 sec, respectively; the calculated half-life value was 2.38 sec. A statistically significant difference was found between the inactivation rates of poliovirus T(1) in the two test systems. This rate difference was attributed primarily to UV dosage and stirring effects. The data indicated that UV radiation effectively inactivated poliovirus T(1) in flowing seawater. These results validate the efficacy of the Kelly-Purdy UV Seawater Treatment Unit for use in commercial depuration systems.


Anomalous drainage of the common bile duct into the fourth portion of the duodenum. Clinical sequelae.
We report two cases of early-childhood anomalous drainage of the common bile duct (CBD) into the fourth portion of the duodenum, which caused recurrent abdominal pain and hyperamylasemia. In both patients, this anomaly was associated with a long common channel between the CBD and the pancreatic duct. The CBD was obstructed by compression from the first portion of the duodenum, which passed anteriorly. Both children required choledochoenteric anastomosis to achieve permanent resolution of the abdominal pain. Elevation of the first portion of the duodenum does not produce permanent relief from symptoms. We believe that these patients represent the first described to have this unusual malformation.


Assessment of intrinsic vulnerability to contamination for Gaza coastal aquifer, Palestine.
Gaza coastal aquifer (GCA) is the major source of fresh water for the 1.5 million residents of Gaza Strip, Palestine. The aquifer is under deteriorating quality conditions mainly due to the excessive application of fertilizers. The intrinsic vulnerability of GCA to contamination was assessed using the well-known DRASTIC method. Detailed analysis of the intrinsic vulnerability map of GCA was carried out and did consider different relationships between the vulnerability indices and the on-ground nitrogen loadings and land use classes. In addition, correlation between vulnerability values and the nitrate concentrations in GCA was studied. Based on the vulnerability analysis, it was found that 10% and 13% of Gaza Strip area is under low and high vulnerability of groundwater contamination, respectively, while more than 77% of the area of Gaza Strip can be designated as an area of moderate vulnerability of groundwater contamination. It was found that the density of groundwater sampling wells for nitrate concentration is high for the moderate and high vulnerability zones. The highest first quartile, median, mean, and third quartile of nitrate concentrations are reported in the high vulnerability zones. Results of sensitivity analysis show a high sensitivity of the high vulnerability index to the depth to water table.


Estimating the number of organisms in quantal assays.
It has been demonstrated by virologists that, when procedural difficulties can be overcome and host variation can be eliminated, dosage-response data from virus assays conform with the one-particle theory of infection for both plaque counts and tissue cultures. Based on this theory, the number of virus particles from quantal virus assays can be estimated. Here a set of tables is presented from which the number of estimated particles can be obtained directly for several dilution factors and a number of dilution levels. Maximum likelihood estimation of particle counts is also illustrated using a computer program that we have prepared.