Fatal toxicity of antidepressant drugs in overdose.
A fatal toxicity index (deaths per million National Health Service prescriptions) was calculated for antidepressant drugs on sale during the years 1975-84 in England, Wales, and Scotland. The tricyclic drugs introduced before 1970 had a higher index than the mean for all the drugs studied (p less than 0.001). In this group the toxicity of amitriptyline, dibenzepin, desipramine, and dothiepin was significantly higher, while that of clomipramine, imipramine, iprindole, protriptyline, and trimipramine was lower. The monoamine oxidase inhibitors had intermediate toxicity, and the antidepressants introduced since 1973, considered as a group, had significantly lower toxicity than the mean (p less than 0.001). Of these newer drugs, maprotiline had a fatal toxicity index similar to that of the older tricyclic antidepressants, while the other newly introduced drugs had lower toxicity indices, with those for mianserin, nomifensine, trazodone, and viloxazine reaching significance. Provided that these drugs are equally effective clinically, serious consideration should be given to prescribing antidepressants with a lower fatal toxicity.


A behavior- and observation-based monitoring process for safety management.
The objective of this paper is to demonstrate that a combination of a behavior-based monitoring process--using an at-risk behavior and unsafe condition observation system--and an observation-based safety adherence monitoring process that can indicate the compliance level with well-defined and agreed safety critical aspects and operational practices and procedures will be an effective safety management tool. This tool herein described represents a particular case, developed by a Praxair Inc. subsidiary in Brazil. Other safety surveillance systems usually adopted in industrial environments can rarely be used on construction sites. They also do not share information, knowledge and skills among the safety staff and other professionals invited to observe, usually covering specific tasks or specific professionals only, not a complete working area, which causes functional observing and monitoring limitations in terms of capturing behaviors and environmental safety issues. This tool also offers a wide range of learning opportunities and continuous improvement.


Diagnostic and therapeutic effects of fluorescence cystoscopy and narrow-band imaging in bladder cancer: a systematic review and network meta-analysis.
This review aims to compare the efficacies of fluorescence cystoscopy, narrow-band imaging (NBI), and white light cystoscopy in the treatment and diagnosis of bladder cancer. The authors searched PubMed, EMbase, Web of Science, and the Cochrane Library from January 1990 to April 2022. A total of 26 randomized controlled studies and 22 prospective single-arm studies were selected. Most patients had nonmuscle-invasive bladder cancer. The study protocol has been registered at PROSPERO. In the pairwise meta-analysis, 5-aminolevulinic acid (5-ALA) reduced the short-term and long-term recurrence rates of bladder cancer compared with white light cystoscopy (WLC); however, no statistical difference was observed in intermediate-term recurrence rates (RR=0.79, 95% CI: 0.57-1.09). Hexaminolevulinic acid and NBI reduced short-term, intermediate-term, and long-term recurrence rates. The sensitivity of 5-ALA, hexaminolevulinic acid, NBI, and WLC for bladder cancer were 0.89 (95% CI: 0.81-0.94), 0.96 (95% CI: 0.92-0.98), 0.96 (95% CI: 0.92-0.98), and 0.75 (95% CI: 0.70-0.79), respectively; however, only NBI had the same specificity as WLC (0.74 vs. 0.74). Compared with WLC, 5-ALA improved the detection rate of carcinoma in situ and Ta stage bladder cancer but had no advantage in T1 stage tumors (OR=2.39, 95% CI:0.79-7.19). Hexaminolevulinic acid and NBI improved the detection rates of all nonmuscular-invasive bladder cancers. In the network meta-analysis, there was no significant difference in either recurrence or detection rates between 5-ALA, hexaminolevulinic acid, and NBI. Fluorescence cystoscopy and NBI are advantageous for treating and diagnosing patients with nonmuscle-invasive bladder cancer.


Endothelial Cell Tetrahydrobiopterin Modulates Sensitivity to Ang (Angiotensin) II-Induced Vascular Remodeling, Blood Pressure, and Abdominal Aortic Aneurysm.
GTPCH (GTP cyclohydrolase 1, encoded by Gch1) is required for the synthesis of tetrahydrobiopterin; a critical regulator of endothelial NO synthase function. We have previously shown that mice with selective loss of Gch1 in endothelial cells have mild vascular dysfunction, but the consequences of endothelial cell tetrahydrobiopterin deficiency in vascular disease pathogenesis are unknown. We investigated the pathological consequence of Ang (angiotensin) II infusion in endothelial cell Gch1 deficient (Gch1fl/fl Tie2cre) mice. Ang II (0.4 mg/kg per day, delivered by osmotic minipump) caused a significant decrease in circulating tetrahydrobiopterin levels in Gch1fl/fl Tie2cre mice and a significant increase in the Nω-nitro-L-arginine methyl ester inhabitable production of H2O2 in the aorta. Chronic treatment with this subpressor dose of Ang II resulted in a significant increase in blood pressure only in Gch1fl/fl Tie2cre mice. This finding was mirrored with acute administration of Ang II, where increased sensitivity to Ang II was observed at both pressor and subpressor doses. Chronic Ang II infusion in Gch1fl/fl Tie2ce mice resulted in vascular dysfunction in resistance mesenteric arteries with an enhanced constrictor and decreased dilator response and medial hypertrophy. Altered vascular remodeling was also observed in the aorta with an increase in the incidence of abdominal aortic aneurysm formation in Gch1fl/fl Tie2ce mice. These findings indicate a specific requirement for endothelial cell tetrahydrobiopterin in modulating the hemodynamic and structural changes induced by Ang II, through modulation of blood pressure, structural changes in resistance vessels, and aneurysm formation in the aorta.


Building meaning in schizophrenia.
The schizophrenia syndrome is clinically characterized by abnormal constructions of meaning during comprehension (delusions), perception (hallucinations), action (disorganized and non-goal-directed behavior) and language production (thought disorder). This article provides an overview of recent studies from our laboratory that have used event-related potentials and functional magnetic resonance imaging to elucidate abnormalities in temporal and spatial patterns of neural activity as meaning is built from language and real-world visual events in schizophrenia. Our findings support the hypothesis that automatic activity across semantic memory spreads further within a shorter period of time in thought-disordered patients, relative to non-thought-disordered patients and healthy controls. Neuroanatomically, increased activity to semantic associates is reflected by inappropriate recruitment of temporal cortices. In building meaning within sentences, the fine balance between semantic memory-based mechanisms and semantic-syntactic integration (dictating "who does what to whom") is disrupted, such that comprehension is driven primarily by semantic memory-based processes. Neuroanatomically, this imbalance is reflected by preserved (and sometimes increased) activity within temporal and inferior prefrontal cortices, but abnormal modulation of dorsolateral prefrontal and parietal cortices. In building meaning across sentences (discourse), patients fail to immediately construct coherence links, but may show inappropriate recruitment of temporal and inferior prefrontal cortices to incoherent discourse, again reflecting inappropriate semantic memory-based processing (abnormal inferencing). Finally, these abnormalities may generalize to real-world visual event comprehension, where patients show reduced neural activity in determining relationships around goal-directed actions, and comprehension is again dominated by semantic memory-based mechanisms.


Comparative survival benefit of currently licensed second or third line treatments for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) negative advanced or metastatic non-small cell lung cancer: a systematic review and secondary analysis of trials.
A review of therapies for advanced cancers licenced by the EMA between 2009 and 2013 concluded that for more than half of these drugs there was little evidence of overall survival or quality of life benefit. Recent years have witnessed a growing number of licensed second-line pharmacotherapies for advanced/metastatic non-small cell lung cancer (NSCLC). With the aim of gauging patient survival benefit, we conducted a systematic review of randomised controlled trials (RCT) and compared survival outcomes from available licensed treatments for patients with advanced/metastatic NSCLC. RCTs of second/third line treatments in participants with advanced/metastatic NSCLC and negative/low expression of Anaplastic Lymphoma Kinase (ALK) and of Epidermal Growth Factor Receptor (EGFR) were included. We searched electronic databases (MEDLINE; EMBASE; Web of Science) from January, 2000 up to July, 2017. Two or more independent reviewers screened bibliographic records, extracted data, and assessed risk of bias of studies. Published Kaplan Meier plots for OS and PFS along with restricted-mean-survival methods and parametric modelling were used to estimate the survival outcomes as mean number of months of survival. Network meta-analysis was undertaken to rank interventions and to make indirect comparisons. We included 11 RCTs with data for 7581 participants that compared nine different drugs. In studies of patients regardless of histology groups, targeted drugs (ramucirumab and nintedanib) yielded small overall survival gains of < 2.5 months over docetaxel, erlotinib provided no benefit, while immunotherapies (atezolizumab and pembrolizumab) delivered 5 to 6 months gain. Studies with patients stratified by histology confirmed the apparent superiority of immunotherapy (nivolumab and atezolizumab) over targeted treatments (ramucirumab, nintedanib, afatinib) providing between about 4 to 8 months OS gain over docetaxel. In network analysis immunotherapies consistently ranked higher than alternatives irrespective of population histology and outcome measure. Our review indicates that nivolumab, pembrolizumab and atezolizumab provide superior survival benefits compared to other licensed drugs for late stage NSCLC. Patient gains from these immunotherapies are substantial compared to the expected average survival with chemotherapy (docetaxel) of < 1 year for people with squamous histology and about 1.25 year for those with non-squamous histology.


Reducing paediatric unintended extubation: A standardized bundle approach.
Unintended extubation (UE) is a serious risk associated with endotracheal intubation. In the paediatric population, UE can lead to significant patient harm. On average, each UE increases ICU and hospital length of stay by 5.5 and 6.5 days respectively and costs an additional $36 000. The international benchmark rate of UE for quality analysis cited in the literature is <1 per 100 ventilator days. The United States organization Solutions for Patient Safety (SPS) developed and introduced a bundle to reduce UE with a goal of ≤0.95 per 100 ventilator days. The aim of this quality improvement project was to determine the baseline rate of UE in a 20-bed mixed medical/surgical PICU in the Pacific Northwest of the United States, implement the SPS bundle for UE prevention, and assess adherence to the bundle, and subsequent rate of UE. The IHI Model for Improvement Plan-Do-Study-Act (PDSA) was used to guide the development, implementation, and assessment of the SPS UE Bundle standardizing the management of endotracheal tubes. Adherence to the bundle was measured through peer-to-peer audits. Rates of adherence and UE were monitored on line charts. Baseline rate of UE was 1.83 per 100 ventilator days; 23 weeks post implementation of the bundle the rate of UE was reduced to 0.38 UE per 100 ventilator days, F(7, 9) = 4.685, p = 0.027. The mean bundle adherence was 92%. This quality improvement initiative confirms that high adherence to the SPS UE Bundle may significantly reduce rates of UE in PICU settings. Use of the SPS evidence-based discrete UE bundle and high adherence to the bundle can standardize practise and may reduce unintended extubation in the paediatric population.


[Study method for registering cardiovascular morbidity with automatic processing of medical data].
Automation of the registration of cardiological diseases provides the basis for creating an automated system of control in cardiology, which may be used to analyse the disease incidence for any length of time and to obtain, whenever required, extensive operative information on the activity of therapeutic and prophylactic establishments. This information will serve for judging the condition of specialized cardiological service on the whole as well as in different territorial and production-shop areas, and in cardiological offices, and for estimating the need in hospitalization according to the forms of cardiological diseases. This, in turn, makes it possible to improve the planning of medical care measures.


Individual (co)variation in standard metabolic rate, feeding rate, and exploratory behavior in wild-caught semiaquatic salamanders.
Repeatability is an important concept in evolutionary analyses because it provides information regarding the benefit of repeated measurements and, in most cases, a putative upper limit to heritability estimates. Repeatability (R) of different aspects of energy metabolism and behavior has been demonstrated in a variety of organisms over short and long time intervals. Recent research suggests that consistent individual differences in behavior and energy metabolism might covary. Here we present new data on the repeatability of body mass, standard metabolic rate (SMR), voluntary exploratory behavior, and feeding rate in a semiaquatic salamander and ask whether individual variation in behavioral traits is correlated with individual variation in metabolism on a whole-animal basis and after conditioning on body mass. All measured traits were repeatable, but the repeatability estimates ranged from very high for body mass (R = 0.98), to intermediate for SMR (R = 0.39) and food intake (R = 0.58), to low for exploratory behavior (R = 0.25). Moreover, repeatability estimates for all traits except body mass declined over time (i.e., from 3 to 9 wk), although this pattern could be a consequence of the relatively low sample size used in this study. Despite significant repeatability in all traits, we find little evidence that behaviors are correlated with SMR at the phenotypic and among-individual levels when conditioned on body mass. Specifically, the phenotypic correlations between SMR and exploratory behavior were negative in all trials but significantly so in one trial only. Salamanders in this study showed individual variation in how their exploratory behavior changed across trials (but not body mass, SMR, and feed intake), which might have contributed to observed changing correlations across trials.


New mitogenome and nuclear evidence on the phylogeny and taxonomy of the highly zoonotic tapeworm Echinococcus granulosus sensu stricto.
Cystic echinococcosis, a zoonotic disease caused by Echinococcus granulosus sensu lato (s. l.), is a significant global public health concern. Echinococcus granulosus s. l. is currently divided into numerous genotypes (G1-G8 and G10) of which G1-G3 are the most frequently implicated genotypes in human infections. Although it has been suggested that G1-G3 could be regarded as a distinct species E. granulosus sensu stricto (s. s.), the evidence to support this is inconclusive. Most importantly, data from nuclear DNA that provide means to investigate the exchange of genetic material between G1-G3 is lacking as none of the published nuclear DNA studies have explicitly included G2 or G3. Moreover, the commonly used relatively short mtDNA sequences, including the complete cox1 gene, have not allowed unequivocal differentiation of genotypes G1-G3. Therefore, significantly longer mtDNA sequences are required to distinguish these genotypes with confidence. The main aim of this study was to evaluate the phylogenetic relations and taxonomy of genotypes G1-G3 using sequences of nearly complete mitogenomes (11,443bp) and three nuclear loci (2984bp). A total of 23 G1-G3 samples were analysed, originating from 5 intermediate host species in 10 countries. The mtDNA data demonstrate that genotypes G1 and G3 are distinct mitochondrial genotypes (separated by 37 mutations), whereas G2 is not a separate genotype or even a monophyletic cluster, but belongs to G3. Nuclear data revealed no genetic separation of G1 and G3, suggesting that these genotypes form a single species due to ongoing gene flow. We conclude that: (a) in the taxonomic sense, genotypes G1 and G3 can be treated as a single species E. granulosus s. s.; (b) genotypes G1 and G3 should be regarded as distinct genotypes only in the context of mitochondrial data; (c) we recommend excluding G2 from the genotype list.


Construction and Production of HIV-VLP Harboring MPER-V3 for Potential Vaccine Study.
Vaccine against HIV-1 is not currently available. In present, Virus like particles (VLPs) as effective strategy was used in several vaccine developing. Two conserved sequences; V3 loop of gp120 and the membrane-proximal external region (MPER) of gp41 are dominant sites for vaccine studies. In this study, we used fusion gene of MPER and V3 to product recombinant VLPs and introduced a novel retroviral VLPs harboring high copy of MPER-V3 for HIV-1 vaccine design. The pEGFP-N1 plasmid harboring MPER-V3 sequence with Vpr linker was constructed. To produce virus-like particles, HEK 293T cells were co-transfected with the recombinant plasmid, pSPAX-2, pMD2-G and pWPXLd plasmids, evaluated by AFM and SEM microscopy and quantified using P24 end-point ELISA assay. Time-course quantification of p24 protein as the characteristics of viral production evidenced for the efficient secretion of virus-like structures (up to 120 ng/ml) to the culture supernatant of transfected cells. Examination of the centrifuge-concentrated VLPs by AFM and SEM microscope, also illustrated particles with spherical morphologies and diameters of around 150 nm that had similar sizes to HIV virions. These data indicated the production of HIV-1 virus-like particles harboring high copy of MPER-V3 that maintained their antigenic structure. These VLPs represented a good implication as a potential vaccine candidate and this guarantees the further investigations towards the assessment of its immunogenicity.


Severely blunted allergen-induced pulmonary Th2 cell response and lung hyperresponsiveness in type 1 transient receptor potential channel-deficient mice.
Transient receptor potential channels (TRPCs) are widely expressed and regulate Ca²⁺ entry in the cells that participate in the pathophysiology of airway hyperreactivity, inflammation, and remodeling. In vitro studies point to a role for TRPC1-mediated Ca²⁺ signaling in several of these cell types; however, physiological evidence is lacking. Here we identify TRPC1 signaling as proinflammatory and a regulator of lung hyperresponsiveness during allergen-induced pulmonary response. TRPC1-deficient (Trpc1(-/-)) mice are hyposensitive to methacholine challenge and have significantly reduced allergen-induced pulmonary leukocyte infiltration coupled with an attenuated T helper type 2 (Th2) cell response. Upon in vitro allergen exposure, Trpc1(-/-) splenocytes show impaired proliferation and T cell receptor-induced IL-2 production. A high number of germinal centers in spleens of Trpc1(-/-) mice and elevated levels of immunoglobulins in their serum are indicative of dysregulated B cell function and homeostasis. Thus we propose that TRPC1 signaling is necessary in lymphocyte biology and in regulation of allergen-induced lung hyperresponsiveness, making TRPC1 a potential target for treatment of immune diseases and asthma.


Mitochondria positioning controls local calcium influx in T cells.
Formation of an immunological synapse (IS) between APC and T cells activates calcium entry through ORAI channels, which is indispensable for T cell activation. Successful proliferation and maturation of naive T cells is possible only if premature inactivation of ORAI channels is prevented. Although it is undisputed that calcium entry through ORAI channels is required for T cell function, it is not known if calcium influx is uniformly distributed over the plasma membrane or if preferential local calcium entry sites (for instance, at the IS) exist. In this study, we show that mitochondrial positioning determines the magnitude of local calcium entry anywhere in the plasma membrane by reducing local calcium-dependent channel inactivation: if mitochondria are close to any given local calcium entry site, calcium influx is large; if they are not close, calcium influx is small. Following formation of the IS, mitochondria are preferentially translocated to the IS in a calcium influx-dependent manner but independent of the exact calcium influx site. Mitochondrial enrichment at the IS favors local calcium entry at the IS without the necessity to enrich ORAI channels at the IS. We conclude that local calcium entry rather than global calcium entry is the preferential mechanism of calcium entry at stable ISs in Th cells.


Children's learning and development in conflict- and crisis-affected countries: Building a science for action.
This paper critically reviews the opportunities and challenges in designing and conducting actionable research on the learning and development of children in conflict- and crisis-affected countries. We approached our review through two perspectives championed by Edward Zigler: (a) child development and social policy and (b) developmental psychopathology in context. The aim of the work was to answer the following questions: What works to enhance children's learning and development in such contexts? By what mechanisms? For whom? Under what conditions? How do experiences and conditions of crisis affect the basic processes of children's typical development? The review is based on a research-practice partnership started in the Democratic Republic of the Congo in 2010 and expanded to research in Niger and Lebanon in 2016. The focus of the research is on the impact of Healing Classrooms (a set of classroom practices) and Healing Classrooms Plus (an additional set of targeted social and emotional learning activities), developed by the International Rescue Committee, on children's academic outcomes and social and emotional learning. We sought to extract lessons from this decade of research for building a global developmental science for action. Special attention is paid to the importance of research-practice partnerships, conceptual frameworks, measurement and methodology. We conclude by highlighting several essential features of a global developmental science for action.


Unravelling proximate cues of mass flowering in the tropical forests of South-East Asia from gene expression analyses.
Elucidating the physiological mechanisms of the irregular yet concerted flowering rhythm of mass flowering tree species in the tropics requires long-term monitoring of flowering phenology, exogenous and endogenous environmental factors, as well as identifying interactions and dependencies among these factors. To investigate the proximate factors for floral initiation of mast seeding trees in the tropics, we monitored the expression dynamics of two key flowering genes, meteorological conditions and endogenous resources over two flowering events of Shorea curtisii and Shorea leprosula in the Malay Peninsula. Comparisons of expression dynamics of genes studied indicated functional conservation of FLOWERING LOCUS T (FT) and LEAFY (LFY) in Shorea. The genes were highly expressed at least 1 month before anthesis for both species. A mathematical model considering the synergistic effect of cool temperature and drought on activation of the flowering gene was successful in predicting the observed gene expression patterns. Requirement of both cool temperature and drought for floral transition suggested by the model implies that flowering phenologies of these species are sensitive to climate change. Our molecular phenology approach in the tropics sheds light on the conserved role of flowering genes in plants inhabiting different climate zones and can be widely applied to dissect the flowering processes in other plant species.


Subaponeurotic or subgaleal fluid collections in infancy: an unusual but distinct cause of scalp swelling in infancy.
Subaponeurotic or subgaleal fluid collection is a rare but important cause of scalp swelling in young infants. Fluid in the subaponeurotic or subgaleal space presents as soft, ill-defined, fluctuant, highly mobile scalp swelling and is not limited by suture lines, which makes it clinically very distinct from other scalp swellings. However, the aetiology of such swelling still remains uncertain but may be related to traumatic labour that manifests after the first few weeks of life. There is no indication for imaging if the condition is diagnosed clinically with confidence. The late subaponeurotic or subgaleal fluid collection resolves spontaneously without any intervention, hence conservative management is the treatment of choice.


Effects of endosulfan on B cells of Langerhans islets in rat pancreas.
Endosulfan is widely used in insect control and it is absorbed by both humans and animals through ingestion, inhalation, and percutaneously. The purpose of this work was to study blood glucose levels and ultrastructural changes that might occur in the pancreas of adult male Wistar rats as a result endosulfan intoxication. The treated group (n = 60) received endosulfan orally via gavage 2.0 mg/kg per day in corn oil for 6 weeks, while the control group (n = 10) was given equal amount of corn oil for the same period. The substances were administrated once a day. Blood glucose levels were significantly increased at the end of 3rd and 4th week (P < 0.05), and 5th and 6th week (P < 0.01) after administration of endosulfan to rats compared with the control group. In electron microscopy studies, at the end of 2nd and 3rd weeks, swelling of mitochondria; at the end of 4th week, vacuoles in cytoplasm; at the end of 5th week, dissolution of mitochondrial matrix; and at the end of 6th week, picnotic nucleus in B cells in Langerhans islet were observed after endosulfan treatment.


[111Indium-thrombocyte scintigraphy and percutaneous transluminal dilatation (angioplasty) of supra-aortic vascular stenoses. A new method for deciding therapy and for follow-up control].
Scintigraphy with 111indium-marked autologous platelets has been used during percutaneous transluminal dilatation of supra-aortic arterial stenoses; there were 14 successful dilatations and one attempted dilatation. The material consisted of nine stenoses of the internal carotid artery, two stenoses at the origin of the vertebral artery and four stenoses of the first part of the left subclavian artery. Deposition of thrombi could be demonstrated by scintigraphy, both before and after catheter dilatation. The value of this method for deciding on the type of treatment and for observing the course of percutaneous dilatation of cerebral vessels is discussed.


Studies of marginal zinc deprivation in rhesus monkeys: infant behavior.
Rhesus monkey infants were marginally deprived of zinc (4 ppm diet) from conception and were compared to controls (100 ppm diet) during the first year of life in development of reflexes and motor patterns, mother-infant interaction, delayed response performance, discrimination learning and reversal, and open field behavior. Deficits in amount and variety of behavior were recorded in deprived infants; spontaneous locomotor activity was 50% below control levels in males at 1 mo of age; spontaneous activity was 7-10% lower in both males and females at 3 mo of age; response latencies were 50% lower than controls at 7-9 mo; failure to reach discrimination reversal criterion was seen in 71% of deprived infants as compared to 10% of controls at 10 mo of age; and abnormally low levels of climbing and exploration were seen in two of six deprived infants at 12 mo of age. No abnormalities in the rate of behavioral development or in emotional adaptability were observed. These and other results suggest that syndromes of lethargy, apathy, and hypoactivity are characteristic of behavioral effects of marginal zinc deprivation in primates.


Chemokine receptor CXCR4 expression in hepatocellular carcinoma patients increases the risk of bone metastases and poor survival.
The chemokine and bone marrow-homing receptor CXCR4 is implicated in metastases of various cancers. This study was conducted to analyze the association of CXCR4 expression with hepatocellular carcinoma (HCC) bone metastasis and patient survival. Tumor tissue from HCC patients with (n = 43) and without (n = 138) bone metastasis was subjected to immunohistochemical staining for CXCR4 using tissue microarrays. Immunoreactivity was evaluated semi-quantitatively. A receiver-operating characteristic-based approach and logistical regression analysis were used to determine the predictive value of clinicopathologic factors, including CXCR4 expression, in bone metastasis. Patient survival was analyzed by Kaplan-Meier curves and log-rank tests. CXCR4 overexpression was detected in 34 of 43 (79.1%) patients with bone metastases and in 57 of 138 (41.3%) without bone metastases. CXCR4 expression correlated with (correlation coefficient: 0.551, P < 0.001) and was predictive of HCC bone metastases (AUC: 0.689; 95%CI: 0.601 - 0.776; P < 0.001). CXCR4 staining intensity correlated with the bone metastasis-free survival (correlation coefficient: -0.359; P = 0.018). CXCR4 overexpression in primary tumors (n = 91) decreased overall median survival (18.0 months vs. 36.0 months, P <0.001). Multivariable analysis identified CXCR4 as a strong, independent risk factor for reduced disease-free survival (relative risk [RR]: 5.440; P = 0.023) and overall survival (RR: 7.082; P = 0.001). CXCR4 expression in primary HCCs may be an independent risk factor for bone metastasis and may be associated with poor clinical outcome.


Role of frequency domain optical spectroscopy in the detection of neonatal brain hemorrhage--a newborn piglet study.
Inability of continuous wave (CW) optical spectroscopy to measure changes in scattering, and the use of an arbitrary rather than an actual baseline, makes the CW method highly susceptible to errors that can lead to a false-positive or false-negative diagnosis. Our objective was to assess whether, and to what extent, the use of quantitative frequency domain spectroscopy would improve our ability to detect and monitor the development of brain hemorrhage. A dual-channel frequency-domain tissue spectrometer (Model 96208, ISS, Inc., Champaign, IL) was used to monitor the development of experimental subcortical and periventricular-intraventricular hemorrhage (IVH) in 10 newborn piglets (blood injection model). The multidistance approach was employed to calculate the absorption and reduced scattering coefficients and hemoglobin changes from the ac, dc, and phase values acquired at four different source-detector distances and at 752 nm and 830 nm. There were significant absorption and scattering changes in the subcortical hematoma (n = 5) and the IVH groups (n = 5). The smallest detectable amount of blood in the brain was 0.04 ml. Changes associated with subcortical hematoma were several times higher than those associated with IVH, and correlated better with the estimated cross-sectional area of the hematoma than with the volume of the injected blood. As opposed to IVH, there was a significant absorption difference between the injured (subcortical hematoma) and normal side of the brain, probably because in case of IVH a significant volume of the injected blood had accumulated/spread beyond the reach of the probe. Clearly, frequency-domain spectroscopy cannot increase our ability to quantify the volume (size) or the oxygenation of the injected blood, especially in the case of IVH. However, the ability to quantify the baseline tissue absorption and scattering would significantly improve diagnostic performance, and may allow for early identification and treatment of neonatal brain hemorrhage.


FIRE AND ICE: The quest for the perfect modality in atrial fibrillation ablation.
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Catheter ablation of atrial fibrillation plays an important role in the management of AF. Radiofrequency ablation is widely used in practice all over the world. Cryoablation has emerged as an alternative method for AF ablation. The FIRE and ICE trial was a non inferiority, multicentre, randomized trial that compared between the two modalities and proved cryoablation to be non inferior to radiofrequency in terms of efficacy and safety. However, the rate of AF recurrence was markedly high in both arms of the study.


Prevention of reperfusional damage from ischemic myocardium.
Reperfusional damage refers to the serious structural, functional, and metabolic derangements commonly observed during restoration of coronary circulation following cardiopulmonary bypass. Damage is believed to result from ischemic injury incurred during aortic cross-clamping and unmasked in the recovery period and/or certain metabolic processes activated during postischemic reperfusion. It has been postulated that reperfusional damage can be minimized or eliminated if normal myocardial metabolic parameters can be maintained or restored before the initiation of reperfusion. Studies have tested a variety of cardioplegic solution compositions and administration modes. However, much controversy exists over the different methods. We have tested the hypothesis that improved myocardial protection during cardioplegia can prevent reperfusional damage and investigated the possibility of achieving optimal myocardial protection. Elective cardiac arrest was induced in isolated perfused rat hearts, under working conditions reported previously. We tested two arresting temperatures (8 degrees C and 28 degrees C), three infusion frequencies (single, double, and multiple dose), and different combinations of cardioplegic additives with demonstrated benefits (glucose, adenosine, creatine, and albumin). Metabolic and hemodynamic functions were used to evaluate the protection of the ischemic myocardium. Glucose (0.5%) and adenosine (1 mmol/L) provided clear benefits under all experimental conditions. Double-dose cardioplegia at 8 degrees C also surpassed the single- and multiple-dose groups. When oxygenated cardioplegic solution containing glucose and adenosine was reinfused for 1 minute after 30 minutes of cross-clamping, no measurable changes were detected after ischemic arrest, as compared with normal hearts. Reperfusional damage was eliminated by this procedure. We concluded that an optimal condition for myocardial preservation during elective cardiac arrest in our model was established.


Hallucinations both in and out of context: An active inference account.
Hallucinations, including auditory verbal hallucinations (AVH), occur in both the healthy population and in psychotic conditions such as schizophrenia (often developing after a prodromal period). In addition, hallucinations can be in-context (they can be consistent with the environment, such as when one hallucinates the end of a sentence that has been repeated many times), or out-of-context (such as the bizarre hallucinations associated with schizophrenia). In previous work, we introduced a model of hallucinations as false (positive) inferences based on a (Markov decision process) formulation of active inference. In this work, we extend this model to include content-to disclose the computational mechanisms behind in- and out-of-context hallucinations. In active inference, sensory information is used to disambiguate alternative hypotheses about the causes of sensations. Sensory information is balanced against prior beliefs, and when this balance is tipped in the favor of prior beliefs, hallucinations can occur. We show that in-context hallucinations arise when (simulated) subjects cannot use sensory information to correct prior beliefs about hearing a voice, but beliefs about content (i.e. the sequential order of a sentence) remain accurate. When hallucinating subjects also have inaccurate beliefs about state transitions, out-of-context hallucinations occur; i.e. their hallucinated speech content is disordered. Note that out-of-context hallucinations in this setting does not refer to inference about context, but rather to false perceptual inference that emerges when the confidence in-or precision of-sensory evidence is reduced. Furthermore, subjects with inaccurate beliefs about state transitions but an intact ability to use sensory information do not hallucinate and are reminiscent of prodromal patients. This work demonstrates the different computational mechanisms that may underlie the spectrum of hallucinatory experience-from the healthy population to psychotic states.


Genetics of adaptation in modern chicken.
We carried out whole genome resequencing of 127 chicken including red jungle fowl and multiple populations of commercial broilers and layers to perform a systematic screening of adaptive changes in modern chicken (Gallus gallus domesticus). We uncovered >21 million high quality SNPs of which 34% are newly detected variants. This panel comprises >115,000 predicted amino-acid altering substitutions as well as 1,100 SNPs predicted to be stop-gain or -loss, several of which reach high frequencies. Signatures of selection were investigated both through analyses of fixation and differentiation to reveal selective sweeps that may have had prominent roles during domestication and breed development. Contrasting wild and domestic chicken we confirmed selection at the BCO2 and TSHR loci and identified 34 putative sweeps co-localized with ALX1, KITLG, EPGR, IGF1, DLK1, JPT2, CRAMP1, and GLI3, among others. Analysis of enrichment between groups of wild vs. commercials and broilers vs. layers revealed a further panel of candidate genes including CORIN, SKIV2L2 implicated in pigmentation and LEPR, MEGF10 and SPEF2, suggestive of production-oriented selection. SNPs with marked allele frequency differences between wild and domestic chicken showed a highly significant deficiency in the proportion of amino-acid altering mutations (P<2.5×10-6). The results contribute to the understanding of major genetic changes that took place during the evolution of modern chickens and in poultry breeding.


Spinal magnetic resonance imaging with reduced specific absorption rate in patients harbouring a spinal cord stimulation device - A single-centre prospective study analysing safety, tolerability and image quality.
Spinal cord stimulation (SCS) is an accepted treatment in patients with failed back surgery (FBS), complex regional pain syndrome (CRPS) and persistent radicular pain following surgery. In order to avoid patient hazards or device malfunction manufacturers advise to abstain from magnetic resonance imaging (MRI) in patients with implanted electrodes or pulse generators. In a prospective study, 13 patients harbouring an implanted Medtronic Spinal Cord Stimulation (SCS) device underwent MRI (1.5 T) of the lumbar (n=13), the cervical (n=2) or the thoracic spine (n=1) following the development of new spinal symptoms. An adapted MRI protocol was used limiting the transmitted energy and specific absorption rate. Tolerability and safety were assessed by means of a standardized patient evaluation form documenting pain on a visual analogue scale (0-10), neurologic deficit, and discomfort during the scan. In addition, overall satisfaction with the examination procedure was rated on a Likert scale (1-5). Image quality was rated independently and blinded to the presence of a SCS device by the radiologist and the surgeon as equivalent, superior or inferior compared to the standard spine MRI examination. None of the 13 patients investigated by the modified spinal MRI protocol experienced new neurological deficits, worsening of symptoms or a defect/malfunction of the implant device. Three patients (23.1 %) reported transient warm sensation in the location of the electrode and in one case intermittent slight tingling in the lower extremities. Overall satisfaction with the examination was 1.13 ± 0.34 according to Likert scale (1-5). The image quality was rated - not statistically significant - slightly inferior to standard lumbar spine imaging (0.82 ± 0.54) with a kappa value of 0.68 between the two investigators. MRI examinations detected relevant and new lesions in 9 (69.2 %) patients which affected treatment in 8 (61.5 %) individuals. Using a protocol with a reduced specific energy absorption rate, spinal MRI examinations in patients with SCS can be considered safe. The current view that neurostimulators are a general contraindication to MR examinations has to be reconsidered in patients with new or progressive spinal symptoms.


The product of the Rhizobium meliloti ilvC gene is required for isoleucine and valine synthesis and nodulation of alfalfa.
Tn5-induced mutants of Rhizobium meliloti that require the amino acids isoleucine and valine for growth on minimal medium were studied. In one mutant, 1028, the defect is associated with an inability to induce nodules on alfalfa. The Tn5 mutation in 1028 is located in a chromosomal 5.5-kb EcoRI fragment. Complementation analysis with cloned DNA indicated that 2.0 kb of DNA from the 5.5-kb EcoRI fragment restored the wild-type phenotype in the Ilv- Nod- mutant. This region was further characterized by DNA sequence analysis and was shown to contain a coding sequence homologous to those for Escherichia coli IlvC and Saccharomyces cerevisiae Ilv5. Genes ilvC and ilv5 code for the enzyme acetohydroxy acid isomeroreductase (isomeroreductase), the second enzyme in the parallel pathways for the biosynthesis of isoleucine and valine. Enzymatic assays confirmed that strain 1028 was a mutant defective in isomeroreductase activity. In addition, it was shown that the ilvC genes of Rhizobium meliloti and E. coli are functionally equivalent. We demonstrated that in ilvC mutant 1028 the common nodulation genes nodABC are not activated by the inducer luteolin. E. coli ilvC complemented both defective properties (Ilv- and Nod-) found in mutant 1028. These findings demonstrate that R. meliloti requires an active isomeroreductase enzyme for successful nodulation of alfalfa.


Noise Robust Recognition of Depression Status and Treatment Response from Speech via Unsupervised Feature Aggregation.
In the presented work, we utilise a noisy dataset of clinical interviews with depression patients conducted over the telephone for the purpose of depression classification and automated detection of treatment response. Compared to most previous studies dealing with depression recognition from speech, our data set does not include a healthy group of subjects that have never been diagnosed with depression. Furthermore, it contains measurements at different time points for individual subjects, making it suitable for machine learning-based detection of treatment response. In our experiments, we make use of an unsupervised feature quantisation and aggregation method achieving 69.2% Unweighted Average Recall (UAR) when classifying whether patients are currently in remission or experiencing a major depressive episode (MDE). The performance of our model matches cutoff-based classification via Hamilton Rating Scale for Depression (HRSD) scores. Finally, we show that using speech samples, we can detect response to treatment with a UAR of 68.1%.


Dopamine release in nucleus accumbens during rewarded task switching measured by [¹¹C]raclopride.
Reward and motivation have positive influences on cognitive-control processes in numerous settings. Models of reward implicate corticostriatal loops and the dopamine (DA) system, with special emphasis on D2 receptors in nucleus accumbens (NAcc). In this study, 11 right-handed males (35-40 years) were scanned with positron emission tomography (PET) in a single [(11)C]raclopride dynamic scan during rewarded and non-rewarded task switching. Rewarded task switching (relative to baseline task switching) decreased [(11)C]raclopride binding in NAcc. Decreasing NAcc [(11)C]raclopride binding was strongly associated with task reaction time measures that reflect individual differences in effort and control strategies. Voxelwise analyses additionally revealed reward-related DA release in anterodorsal caudate, a region previously associated with task-switching. These PET findings provide evidence for striatal DA release during motivated cognitive control, and further suggest that NAcc DA release predicts the task reaction time benefits of reward incentives.


Darbepoetin alfa administered once every three weeks for the treatment of anemia in elderly patients with non-myeloid tumors receiving chemotherapy.
The present study aims to describe the hematological response to darbepoetin alfa (DA) under daily clinical practice conditions in anemic elderly patients with non-myeloid tumors receiving chemotherapy. This was a prospective, observational, multicenter study in elderly (≥65 years) patients with non-myeloid cancer receiving DA (500 μg every 3 weeks) for chemotherapy-induced anemia (hemoglobin [Hb] level ≤11.0 g/dL). A total of 102 anemic patients with solid tumors and 51 with hematological malignancies were included in 28 centers in Spain. Mean age (±SD) was 73.4 (±5.8) years, and mean baseline Hb level was 10.0 (±0.8) g/dL. DA was administered for a median of 8 weeks. Of the 115 subjects with a post-baseline Hb value, the percentage of patients who achieved a hematopoietic response (Hb increase ≥2 g/dL or reaching ≥12 g/dL without transfusions in the previous 28 days) was 69.7% (95% CI 56.1% to 83.3%). Functional Assessment of Cancer Therapy-Fatigue subscale scores increased during the study (median change 1.0 [Q1 -5.0, Q3 9.0], P = 0.04). One patient (0.7%) experienced a non-serious adverse reaction (cutaneous rash). The study results suggest that DA is an effective and well-tolerated therapy for the treatment of chemotherapy-induced anemia in elderly patients.


Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains.
Prions propagate as multiple strains in a wide variety of mammalian species. The detection of all such strains by a single ultrasensitive assay such as Real Time Quaking-induced Conversion (RT-QuIC) would facilitate prion disease diagnosis, surveillance and research. Previous studies have shown that bank voles, and transgenic mice expressing bank vole prion protein, are susceptible to most, if not all, types of prions. Here we show that bacterially expressed recombinant bank vole prion protein (residues 23-230) is an effective substrate for the sensitive RT-QuIC detection of all of the different prion types that we have tested so far--a total of 28 from humans, cattle, sheep, cervids and rodents, including several that have previously been undetectable by RT-QuIC or Protein Misfolding Cyclic Amplification. Furthermore, comparison of the relative abilities of different prions to seed positive RT-QuIC reactions with bank vole and not other recombinant prion proteins allowed discrimination of prion strains such as classical and atypical L-type bovine spongiform encephalopathy, classical and atypical Nor98 scrapie in sheep, and sporadic and variant Creutzfeldt-Jakob disease in humans. Comparison of protease-resistant RT-QuIC conversion products also aided strain discrimination and suggested the existence of several distinct classes of prion templates among the many strains tested.


Failing: Nursing Student Perceptions and Insights for Success.
Nursing student success is important to students, faculty, higher education, and health care as the nursing shortage continues. However, baccalaureate nursing graduation rates average 80 to 84 (National League for Nursing, n.d.; Texas Center for Nursing Workforce Studies, 2017). Research exploring increased student success is attributed to competitive admission of students highly successful in prerequisite coursework. There is a gap in the literature regarding students' experiences of failure in didactic nursing courses. This article explores why previously successful students experience didactic failure in BSN course.


Epidemiology of Severe Acute Diarrhea in Patients Requiring Hospital Admission.
Information on the epidemiology and susceptibility patterns of main pathogens causing severe acute diarrhea may help to reduce inappropriate antimicrobial use in emergency departments. We sought to investigate the micro-organisms causing severe acute diarrhea in patients requiring hospital admission by means of a commercial multiple polymerase chain reaction system. Between November 2016 and October 2018 we studied 132 patients with acute diarrhea who required hospital admission at a 250-bed hospital in Spain. Demographic, clinical, analytical, and microbiological data were collected from the medical records. Stool samples were processed using a rapid commercial multiple polymerase chain reaction system (FilmArray Gastrointestinal Panel), stool culture, and standard microbiological procedures. The median age (range) of patients was 45.5 (0.1-92) years, and 50% were male; 46.2% presented with fever, 62.8% presented with vomiting, and 12.9% presented with rectal bleeding. At least 1 enteric pathogen was identified in 93 (70.4%) patients; 28 (21.2%) patients had >1 micro-organism. FilmArray Gastrointestinal Panel results were available in a median (range) of 1 (0-3) days. The micro-organisms most frequently identified were 24 cases of Campylobacter species, 20 cases of Clostridioides difficile producing toxin A or toxin B, 20 cases of Salmonella species, 12 cases of rotavirus, and 30 cases of different types of pathogenic Escherichia coli. Among the cases of C. difficile, 12 (60%) were community-acquired and 8 (40%) had an undetermined origin. The FilmArray Gastrointestinal Panel system provides fast and reliable results and could be useful to select the most appropriate antimicrobial based on local susceptibilities until the results of the cultures are available.


Paraquat-activated BV-2 microglia induces neuroinflammatory responses in the neuron model through NF-κB signaling pathway.
Paraquat (PQ), a non-selective contact herbicide, has been generally accepted as one of the environmental neurotoxicants. Despite the direct evidence that PQ could induce inflammation responses in microglia, little is known about the effects of the inflammatory microglia on neurons. Thus in the present study, mouse primary cortical neurons and PC12 cells, widely-used in vitro neuron models for neurotoxicity research were applied to investigate the neuroinflammatory effects of PQ-activated microglia on neurons. We observed that the secretion levels of TNF-α and IL-6 in PC12 cells were markedly increased upon treatment with the supernatants of inflammatory BV2 microglia, and NF-κB p65 protein expression was also elevated. Specific inhibition of NF-κB by PDTC dramatically attenuated the increase of TNF-α and IL-6 release. These results suggested that PQ-induced inflammatory microglia exerts secondary inflammatory effects on neurons through activation of NF-κB pathway.


Environmental Factors Promoting Neural Plasticity: Insights from Animal and Human Studies.
We do not all grow older in the same way. Some individuals have a cognitive decline earlier and faster than others who are older in years but cerebrally younger. This is particularly easy to verify in people who have maintained regular physical activity and healthy and cognitively stimulating lifestyle and even in the clinical field. There are patients with advanced neurodegeneration, such as Alzheimer's disease (AD), that, despite this, have mild cognitive impairment. What determines this interindividual difference? Certainly, it cannot be the result of only genetic factors. We are made in a certain manner and what we do acts on our brain. In fact, our genetic basis can be modulated, modified, and changed by our experiences such as education and life events; daily, by sleep schedules and habits; or also by dietary elements. And this can be seen as true even if our experiences are indirectly driven by our genetic basis. In this paper, we will review some current scientific research on how our experiences are able to modulate the structural organization of the brain and how a healthy lifestyle (regular physical activity, correct sleep hygiene, and healthy diet) appears to positively affect cognitive reserve.


Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice.
Mice lacking natriuretic peptide receptor A (NPRA) have marked cardiac hypertrophy and chamber dilatation disproportionate to their increased blood pressure (BP), suggesting, in support of previous in vitro data, that the NPRA system moderates the cardiac response to hypertrophic stimuli. Here, we have followed the changes in cardiac function in response to altered mechanical load on the heart of NPRA-null mice (Npr1-/-). Chronic treatment with either enalapril, furosemide, hydralazine, or losartan were all effective in reducing and maintaining BP at normal levels without affecting heart weight/body weight. In the reverse direction, we used transverse aortic constriction (TAC) to induce pressure overload. In the Npr1-/- mice, TAC resulted in a 15-fold increase in atrial natriuretic peptide (ANP) expression, a 55% increase in left ventricular weight/body weight (LV/BW), dilatation of the LV, and significant decline in cardiac function. In contrast, banded Npr1+/+ mice showed only a threefold increase in ANP expression, an 11% increase in LV/BW, a 0.2 mm decrease in LV end diastolic dimension, and no change in fractional shortening. The activation of mitogen-activated protein kinases that occurs in response to TAC did not differ in the Npr1+/+ and Npr1-/- mice. Taken together, these results suggest that the NPRA system has direct antihypertrophic actions in the heart, independent of its role in BP control.


Clinical review: Optimal dose of continuous renal replacement therapy in acute kidney injury.
Continuous renal replacement therapy (CRRT) is the preferred treatment for acute kidney injury in intensive care units (ICUs) throughout much of the world. Despite the widespread use of CRRT, controversy and center-specific practice variation in the clinical application of CRRT continue. In particular, whereas two single-center studies have suggested survival benefit from delivery of higher-intensity CRRT to patients with acute kidney injury in the ICU, other studies have been inconsistent in their results. Now, however, two large multi-center randomized controlled trials - the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study and the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study - have provided level 1 evidence that effluent flow rates above 25 mL/kg per hour do not improve outcomes in patients in the ICU. In this review, we discuss the concept of dose of CRRT, its relationship with clinical outcomes, and what target optimal dose of CRRT should be pursued in light of the high-quality evidence now available.


Synchronous wearable wireless body sensor network composed of autonomous textile nodes.
A novel, fully-autonomous, wearable, wireless sensor network is presented, where each flexible textile node performs cooperative synchronous acquisition and distributed event detection. Computationally efficient situational-awareness algorithms are implemented on the low-power microcontroller present on each flexible node. The detected events are wirelessly transmitted to a base station, directly, as well as forwarded by other on-body nodes. For each node, a dual-polarized textile patch antenna serves as a platform for the flexible electronic circuitry. Therefore, the system is particularly suitable for comfortable and unobtrusive integration into garments. In the meantime, polarization diversity can be exploited to improve the reliability and energy-efficiency of the wireless transmission. Extensive experiments in realistic conditions have demonstrated that this new autonomous, body-centric, textile-antenna, wireless sensor network is able to correctly detect different operating conditions of a firefighter during an intervention. By relying on four network nodes integrated into the protective garment, this functionality is implemented locally, on the body, and in real time. In addition, the received sensor data are reliably transferred to a central access point at the command post, for more detailed and more comprehensive real-time visualization. This information provides coordinators and commanders with situational awareness of the entire rescue operation. A statistical analysis of measured on-body node-to-node, as well as off-body person-to-person channels is included, confirming the reliability of the communication system.


Technical skills rotation for general surgery residents.
Technical skills are an important part of any general surgery residency curriculum. With the demands of limited work weeks, it is imperative that educators create novel methods of teaching technical skills to their residents. Our program utilizes a dedicated month to help accomplish this. This study hypothesized that general surgery residents would report a positive effect of a dedicated technical skills rotation. Residents who had undergone a 1 mo rotation in technical skills during their first year were asked to fill out a survey concerning their experience. During the 1-mo rotation, the residents had almost no clinical responsibilities. Teaching of technical skills was performed with various activities, including video content (VC), virtual reality simulators (VR), open foam procedures (OF), laparoscopic box trainers (BT), surgical equipment in-service (SE), and animate sessions (AS). Responses were given on a Likert scale (1-10) with higher numbers being more positive responses. There were seven residents in this study. The residents gave a very positive response to the overall rotation (9.4) and exposure to laparoscopic procedures (9.6). The other responses were enthusiastic as well: exposure to open procedures (8.9) and preparation for operative room (9.4). After their rotation, the residents were comfortable performing a laparoscopic cholecystectomy (9.2), a hand-sewn anastomosis (8.7), and a stapled anastomosis (9.4). The residents found theses activities helpful in increasing order: VC (7.8), VR (8.0), BT (9.0), ES (9.7), OF (9.8), and AS (9.8). A 1-mo dedicated technical skills rotations was perceived to be extremely positive by the residents. The residents felt very comfortable performing a laparoscopic cholecystectomy, a hand-sewn anastomosis, and a stapled anastomosis. With the 80-h work week, alternatives to learning technical skills in the operating room are essential. Further studies need to be performed to determine if this rotation aids in accomplishing this goal.


[Miliary tuberculosis presented as a sacroiliitis: a case report].
Miliary tuberculosis is a clinical picture due to hematogenous dissemination of a very large amount of bacilli. We present a case with miliary tuberculosis in which the diagnosis and treatment was delayed due to focusing on complaints about the sacroiliac joint. The 28-year-old male patient was admitted with a five-month history of pain in his left sacroiliac joint which was not traumatic. As a definitive diagnosis could not be reached by means of laboratory tests performed, an open biopsy was planned. In the chest X-ray obtained for routine preoperative evaluation, diffuse, bilateral opacities with a 1-2 mm radius were detected and the case was diagnosed with miliary tuberculosis. Miliary tuberculosis is a disease involving multiple organs and systems and treatment can be started empirically as microbiologic verification is difficult. Sacroiliac joint infections are rare and diagnosis is often delayed. The diagnosis of bone and joint tuberculosis is hard because of relative rarity of the disorder, the wide variety in clinical presentation, low suspicion of the examining physician, and rare diagnostic findings on radiographs. This case report highlights the importance of continued awareness for early detection and treatment of a tuberculous sacroiliac joint infection.


How to Name and Classify Your Phage: An Informal Guide.
With this informal guide, we try to assist both new and experienced phage researchers through two important stages that follow phage discovery; that is, naming and classification. Providing an appropriate name for a bacteriophage is not as trivial as it sounds, and the effects might be long-lasting in databases and in official taxon names. Phage classification is the responsibility of the Bacterial and Archaeal Viruses Subcommittee (BAVS) of the International Committee on the Taxonomy of Viruses (ICTV). While the BAVS aims at providing a holistic approach to phage taxonomy, for individual researchers who have isolated and sequenced a new phage, this can be a little overwhelming. We are now providing these researchers with an informal guide to phage naming and classification, taking a "bottom-up" approach from the phage isolate level.


Synthesis of 2.3 mg/ml of protein with an all Escherichia coli cell-free transcription-translation system.
Cell-free protein synthesis is becoming a useful technique for synthetic biology. As more applications are developed, the demand for novel and more powerful in vitro expression systems is increasing. In this work, an all Escherichia coli cell-free system, that uses the endogenous transcription and translation molecular machineries, is optimized to synthesize up to 2.3 mg/ml of a reporter protein in batch mode reactions. A new metabolism based on maltose allows recycling of inorganic phosphate through its incorporation into newly available glucose molecules, which are processed through the glycolytic pathway to produce more ATP. As a result, the ATP regeneration is more efficient and cell-free protein synthesis lasts up to 10 h. Using a commercial E. coli strain, we show for the first time that more than 2 mg/ml of protein can be synthesized in run-off cell-free transcription-translation reactions by optimizing the energy regeneration and waste products recycling. This work suggests that endogenous enzymes present in the cytoplasmic extract can be used to implement new metabolic pathways for increasing protein yields. This system is the new basis of a cell-free gene expression platform used to construct and to characterize complex biochemical processes in vitro such as gene circuits.


Exploring the mediating effect of creativity on the relationship between family capital and academic achievement in geography.
This study examined the relationship between family capital (FC) and academic achievement in geography along with the mediating role of creativity. The main objective was to determine if FC is a positive predictor of creativity and geographic achievement, and whether creativity completely or partially mediates the relationship between FC and geographic achievement. 1268 high school students participated in this study using the Family Capital Questionnaire (FCQ), the Innovative Behavior Scale (IBS), and students' class geography scores. SPSS 26 and Amos software were used to analyze the descriptive statistics and the correlation between the main variables. The mediating role of creativity was tested using PROCESS version 4. The correlation analyses showed that FC positively affected academic achievement in geography (β = 0.382, SE = 0.019). Creativity also demonstrated a positive effect on geography academic achievement (β = 0.376, SE = 0.022). The mediation analysis showed that creativity mediated and buffered the relationship between FC and academic achievement in geography. Thus, FC directly affected students' academic achievement in geography and indirectly affected their creativity. This clearly demonstrates that student characteristics and the external environment should be emphasized in geography education, while placing a strong focus on cultivating individual creativity.


Activation of hsr203, a plant gene expressed during incompatible plant-pathogen interactions, is correlated with programmed cell death.
hsr203J is a tobacco gene whose activation is rapid, highly localized, and specific for incompatible interactions between tobacco and the bacterial pathogen Ralstonia solanacearum. The effect of other hypersensitive response (HR)-inducing pathogens and elicitors has been tested with transgenic plants containing the hsr203J promoter-GUS reporter gene fusion, and confirms the generality of the preferential inducibility of the hsr203J gene promoter during incompatible interactions: bacterial and viral pathogens inducing an HR in tobacco were able to induce the promoter fusion, as were inducers of HR-like responses such as harpin, elicitins, and PopA1 proteins. A tomato hsr203 homologous cDNA was isolated (Lehsr203) and used to examine the effect of avr gene products on the expression of such genes. Lehsr203 was shown to be rapidly and transiently induced in leaves of the tomato Cf-9 line, following Avr9 product infiltration, but not in those of the Cf-0 line. Among potential effectors of HR or resistance such as H2O2, salicylic acid, methyl jasmonate, and 2,6-dichloro-isonicotinic acid (INA), none is able to induce a significant increase in promoter activation. In contrast, heavy metals that cause leaf necrosis can trigger such an activation. In addition, hsr203-GUS fusion expression is detected in transgenic tobacco lines expressing the bO gene and exhibiting spontaneous HR-like lesions. Taken together, these results demonstrate a strong correlation between hsr203 and genetically controlled cell death in tobacco and tomato. The expression of this gene should be a useful marker for programmed cell death occurring in response not only to diverse pathogens, but also to diverse death-triggering extracellular agents.


Electrochemical behavior of the antifungal agents itraconazole, posaconazole and ketoconazole at a glassy carbon electrode.
The electrochemical behavior of the azole antifungal agents itraconazole, posaconazole and ketoconazole has been investigated at a glassy carbon working electrode using cyclic voltammetry. All measurements were carried out in a supporting electrolyte solution consisting of a 1:1 (v/v) mixture of 0.1 mol L(-1) sodium phosphate buffers and acetonitrile at various substance concentrations and pH values. An amperometric cell with a three electrode system consisting of a working electrode, a palladium reference electrode and a platinum disk as the auxiliary electrode was used in all experiments. All azoles showed a similar electrochemical behavior involving two reactions. An irreversible oxidation occurred at potentials of about 0.5V. A reduction peak was detected at potentials between -0.28V and -0.14V with an associated oxidation peak, which was observed in consecutive repeated measurements at potentials between -0.03 and 0.28 V. The reduction and corresponding oxidation can be regarded as a quasi-reversible process. The proposed reaction mechanisms are an irreversible oxidation of the piperazine moiety at higher potentials as well as a reduction at lower potentials of the carbonyl group of the triazolone moiety in the case of itraconazole and posaconazole or a reduction of the methoxy group of ketoconazole.


Modulation of vaccine response by concomitant probiotic administration.
Evidence suggests that probiotic bacteria modulate both innate and adaptive immunity in the host, and in some situations can result in reduced severity of common illnesses, such as acute rotavirus infection and respiratory infections. Responses to vaccination are increasingly being used to provide high quality information on the immunomodulatory effects of dietary components in humans. The present review focuses on the effect of probiotic administration upon vaccination response. The majority of studies investigating the impact of probiotics on responses to vaccination have been conducted in healthy adults, and at best they show modest effects of probiotics on serum or salivary IgA titres. Studies in infants and in elderly subjects are very limited, and it is too early to draw any firm conclusions regarding the potential for probiotics to act as adjuvants in vaccination. Although some studies are comparable in terms of duration of the intervention, age and characteristics of the subjects, most differ in terms of the probiotic selected. Further well designed, randomized, placebo-controlled studies are needed to understand fully the immunomodulatory properties of probiotics, whether the effects exerted are strain-dependent and age-dependent and their clinical relevance in enhancing immune protection following vaccination.


Gambling participation and social support among older adults: a longitudinal community study.
The purpose of this preliminary study was to examine associations between leaving home to engage in bingo or gambling activity and indices of physical and mental health and social support among a representative community cohort of 1016 elderly people. Cross-sectional and longitudinal data gathered from a prospective epidemiological study in a rural, low socio-economic status, area of Pennsylvania was employed. The cohort had a mean age of 78.8 (SD = 5.1) (range 71-97) and participated in three consecutive biennial "waves" of data collection. Nearly half (47.7) of the cohort reported gambling. To predict gambling, the independent variables included age, sex, education, employment, social support, depressive symptoms, self-rated health, alcohol use, cigarette use, and cognitive functioning. In cross-sectional, univariate analyses, gambling was associated with younger age, sex (male), fewer years of education, greater social support, lower depression scores, better self-rated health, alcohol use in the past year, and higher cognitive functioning. In a cross-sectional multiple regression model, younger age, greater social support, and alcohol use in the past year remain strongly and independently associated with gambling activity. Longitudinally, age, sex, social support, alcohol use, and gambling are predictive of future gambling activity. The results revealed that gambling may offer a forum of social support to older adults who are often isolated as they age.


Preliminary report of postoperative complications of phacoemulsification in Pugs: A multicenter retrospective study of 32 cases.
To compare complication rates and visual outcomes following phacoemulsification in Pugs versus dogs of other breeds. Thirty-two pure-bred Pugs (55 eyes) and 32 dogs of other breeds (56 eyes) undergoing phacoemulsification. Multi-institutional retrospective medical record review of perioperative factors, postoperative complications, and visual outcomes. The reference population of dogs of varying breeds included surgical cases following each Pug case at the same institutions. Perioperative risk factors and postoperative complication rates were compared between the two populations. Pigmentary keratitis and diabetes mellitus were the most common preoperative comorbidities, found in 75% (P < .001) and 72% (P = .12) of Pugs, respectively. No perioperative factors were significantly associated with postoperative complications in Pugs. Postoperative complication rates were similar between groups; however, the most common complication in Pugs was corneal ulceration (15% of operated eyes), whereas glaucoma was most common in the reference population (13% of operated eyes). Three months postoperatively, vision was preserved in 91% of eyes of Pugs (50/55) and 95% of the reference population (53/56). One year postoperatively, 80% (32/40) of Pug eyes and 82% (28/34) of eyes in the reference population remained sighted. Comorbidities and complications of cataract surgery in Pugs of this study demonstrate a predisposition for corneal disease. This highlights the importance of preoperative evaluation of factors associated with PK and corneal clarity, and postoperative monitoring for corneal ulceration in this breed.


Alzheimer's Association Project VITAL: A Florida Statewide Initiative Using Technology to Impact Social Isolation and Well-Being.
Lack of social engagement and the resulting social isolation can have negative impacts on health and well-being, especially in senior care communities and for those living with dementia. Project VITAL leverages technology and community resources to create a network for connection, engagement, education, and support of individuals with dementia and their caregivers, and explores the impact of these interventions in reducing feelings of social isolation and increasing mood among residents during the COVID-19 pandemic. Through two phases, 600 personalized Wi-Fi-enabled iN2L tablets were distributed to 300 senior care communities (55% assisted living communities, 37% skilled nursing communities, 6% memory care communities, and 2% adult family-care homes) to connect and engage residents and their families. Different phases also included Project ECHO, a video-based learning platform, Alzheimer's Association virtual and online education and support for family caregivers, evidence-based online professional dementia care staff training and certification, and Virtual Forums designed to explore ways to build sustainable, scalable models to ensure access to support and decrease social isolation in the future. Tablet usage was collected over an 11-month period and an interim survey was designed to assess the effectiveness of the tablets, in preventing social isolation and increasing mood among residents during the COVID-19 pandemic. A total of 105 care community staff (whose community used the tablets) completed the survey and overall, these staff showed a high level of agreement to statements indicating that residents struggled with loneliness and mood, and that the tablet was useful in improving loneliness and mood in residents and allowing them to stay in touch with family and friends. Additional positive results were seen through a variety of other responses around the tablets and Project ECHO. Overall, the tablets were shown to be an effective way to engage residents and connect them with friends and family, as well as being a useful tool for staff members. A third phase is currently underway in the homes of people with dementia and their family caregivers, which includes tablets and direct access to Alzheimer's Association virtual and online education and support programs.


Patient Care Documentation in the Secondary School Setting: Unique Challenges and Needs.
Athletic trainers (ATs) recognize patient care documentation as an important part of clinical practice. However, ATs using 1 electronic medical record (EMR) platform reported low accountability and lack of time as barriers to documentation. Whether ATs using paper, other EMRs, or a combined paper-electronic system exhibit similar behaviors or experience similar challenges is unclear. To explore ATs' documentation behaviors and perceived challenges while using various systems to document patient care in the secondary school setting. Qualitative study. Individual telephone interviews. Twenty ATs (12 women, 8 men; age = 38 ± 14 years; clinical experience = 15 ± 13 years; from National Athletic Trainers' Association Districts 2, 3, 6, 7, 8, 9, and 10) were recruited via purposeful and snowball-sampling techniques. Two investigators conducted semistructured interviews, which were audio recorded and transcribed verbatim. Following the consensual qualitative research tradition, 3 researchers independently coded transcripts in 4 rounds using a codebook to confirm codes, themes, and data saturation. Multiple researchers, member checking, and peer reviewing were the methods used to triangulate data and enhance trustworthiness. The secondary school setting was central to 3 themes. The ATs identified challenges to documentation, including lack of time due to high patient volume and multiple providers or locations where care was provided. Oftentimes, these challenges affected their documentation behaviors, including the process of and criteria for whether to document or not, content documented, and location and timing of documentation. To enhance patient care documentation, ATs described the need for more professional development, including resources or specific guidelines and viewing how documentation has been used to improve clinical practice. Challenges particular to the secondary school setting affected ATs' documentation behaviors, regardless of the system used to document care. Targeted professional development is needed to promote best practices in patient care documentation.


Design of best management practice applications for diffuse phosphorus pollution using interactive GIS.
The paper presents a complex environmental engineering tool, which is appropriate to support decision making in watershed management. The PhosFate tool allows planning best management practices (BMPs) in catchments and simulating their possible impacts on immissions. The method has two parts: (a) a simple phosphorus (P) fate model to calculate diffuse P emissions and their surface transport, and (b) an interactive tool to design BMPs in small catchments. The fate model calculates diffuse P emissions via surface pathways. It is a conceptual, distributed parameter and long-term (annual) average model. The model also follows the fate of emitted P from each cell to the catchment outlets and calculates the field and in-stream retention. The fate model performed well in the Zala River catchment as a case study. Finally, an interactive design tool was developed to plan BMPs in the catchments and simulate their possible impacts on diffuse P fluxes. Different management scenarios were worked out and their effects evaluated and compared to each other. The results show that the approach is suitable to test BMP scenarios at small catchment scale.


Evidence and the industrialization of medicine.
Medicine is changing rapidly. In part, this is due to the accumulation of discoveries in biomedical science. However, this is not sufficient to explain the changes clinicians see. Whereas once medical advance concerned discoveries external to clinical practice (such as the identification of a causative microorganism or gene), medical practice itself is now a subject of study. What clinicians know, how they acquire knowledge, and how knowledge is distributed are all subjects of scrutiny. In short, medicine is being industrialized: we can see the twin changes of specialization, and the desire to codify practice such that those with different educational backgrounds can undertake a clinical role. Key to such change is the role played by evidence. Whereas once natural science was seen to determine clinical practice, this view is now known to be mistaken. How we can formally combine evidence from different traditions is, despite the claims of the evidence-based medicine movement, as yet unresolved.


Cortical differentiation for nouns and verbs depends on grammatical markers.
Here we address the contentious issue of how nouns and verbs are represented in the brain. The co-occurrence of noun and verb deficits with damage to different neural regions has led to the view that they are differentially represented in the brain. Recent neuroimaging evidence and inconsistent lesion-behavior associations challenge this view. We have suggested that nouns and verbs are not differentially represented in the brain, but that different patterns of neural activity are triggered by the different linguistic functions carried by nouns and verbs. We test these claims in a functional magnetic resonance imaging study using homophones -- words which function grammatically as nouns or verbs but have the same form and meaning -- ensuring that any neural differences reflect differences in grammatical function. Words were presented as single stems and in phrases in which each homophone was preceded by an article to create a noun phrase (NP) or a pronoun to create a verb phrase (VP), thus establishing the word's functional linguistic role. Activity for single-word homophones was not modulated by their frequency of usage as a noun or verb. In contrast, homophones marked as verbs by appearing in VPs elicited greater activity in the left posterior middle temporal gyrus (LpMTG) compared to homophones marked as nouns by occurring in NPs. Neuropsychological patients with grammatical deficits had lesions which overlapped with the greater LpMTG activity found for VPs. These results suggest that nouns and verbs do not invariably activate different neural regions; rather, differential cortical activity depends on the extent to which their different grammatical functions are engaged.


Gastrointestinal microbial population of turkey (Meleagris gallopavo) affected by hemorrhagic enteritis virus.
Hemorrhagic enteritis (HE) is an acute viral disease that affects avian species, particularly turkeys, compromising their commercial production and having a negative effect on animal welfare. Turkey adenovirus 3 (TAdV-3), is the main causal agent of the disease. In this study, we considered 3 groups of turkeys to achieve 2 purposes: 1) A preliminary investigation on the microbiota content in the 4 parts of healthy turkey's intestine (group A), namely duodenum, jejunum, ileum, and ceca was done; 2) an investigation on the relationship between natural infections with TAdV-3 and the intestinal microbiota in the jejunum, where HE mostly develops, comparing group A with animals with molecular positivity for the virus and with clinical signs of HE (group B) and animals with molecular positivity for the virus but without clinical signs (group C). Massive sequencing of the hypervariable V1-V2 regions of 16S rRNA gene and QIIME 1.9.1 software analysis was performed, and operation taxonomic units (OTUs) were classified into 4 abundant phyla: Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. The microbial population of small intestine was distributed almost homogeneously in the healthy turkeys, and Firmicutes was the prevalent phylum (79.85% in duodenum, 89.57% in jejunum and 99.28% in ileum). As compared with small intestine, ceca microbial community was much more heterogeneous: Firmicutes (48.03%), Bacteroidetes (33.60%) and Proteobacteria (12.32%). In the natural infections of HEV, the main bacterial families were Bacteroidaceae (Bacteroidetes) and Peptostreptococcaceae (Firmicutes), uniquely detected in group B and C. Also Clostridiaceae (Firmicutes) was detected, uniquely in group B.


Collaborative efforts support poor elderly. A nursing center teams up with area churches to care for the elderly in their homes.
In many communities across the United States today, churches and hospitals are forming alliances to better serve the needs of the elderly. Bon Secours Hospital-Villa Maria Nursing Center in North Miami, FL, sponsors programs that deter institutionalization. Villa Maria took these efforts one step further in September 1990 with the development of Project Good Help, a church-based outreach program that provides support services to help the poor, frail elderly continue independent living in the community. Villa Maria has coordinated the project with churches because they share a sense of mission. Only churches in areas where many needy elderly persons live are selected to participate in Project Good Help. Areas that lack services are given priority. Project Good Help often coordinates with other professional social service agencies to provide assistance. Catholic Community Services, for example, focuses on nutrition, and Project Good Help focuses on assessing unmet social service needs. The two community groups refer clients to one another. Project Good Help demonstrates that the healthcare and church communities can work together in innovative ways to provide cost-effective community service when they share a mission of caring for the poor and the elderly and are mutually supportive.


Amino acids at the exposed C-terminus of the S coat protein of cowpea mosaic virus play different roles in particle formation and viral systemic movement.
The icosahedral capsid of cowpea mosaic virus is formed by 60 copies of the large (L) and small (S) coat protein subunits. The 24-amino-acid C-terminal peptide of the S coat protein can undergo proteolytic cleavage without affecting particle stability or infectivity. Mutagenic studies have shown that this sequence is involved in particle assembly, virus movement, RNA encapsidation and suppression of gene silencing. However, it is unclear how these processes are related, and which part(s) of the sequence are involved in each process. Here, we have analysed the effect of mutations in the C-terminal region of the S protein on the assembly of empty virus-like particles and on the systemic movement of infectious virus. The results confirmed the importance of positively charged amino acids adjacent to the cleavage site for particle assembly and revealed that the C-terminal 11 amino acids are important for efficient systemic movement of the virus.


[Androgen-producing steroid cell ovarian tumor. Report of a case].
Ovarian Tumors with Endocrine Repercussion make-up 5% of neoplasms in this gland, occupying the first place are the estrogen-producing tumors, in the second place are the androgen-producing tumors, progesterone, corticosteroids and renin are exceptional. In these tumors' nomenclature has existed a kind of synonyms that create confusion about their histogenesis and their difficult use in the literature. A 23 yr-old woman with opsomenorrhea of several years evolution, secondary amenorrhea, deep voice and progressive hirsutism. Weight: 98.500 kg. Height: 1.74 m. Body Mass Index (BMI): 32.61 (kg/m2). Vellus hair in the face (beard and moustache), android distribution in abdomen, forearms, thighs and legs (Ferriman score of 20), acne and bilateral breast involution. All paraclinic exams were negative. Human chorionic gonadotropin quantification in urine of 24 hours was negative. X-Ray: Right ovarian tumor was demonstrated with pelvic ultrasound and computerized axial tomography of abdomen. Cytogenetic study expressed 46 XX chromosomes. Presurgery endocrinologic studies were: total and free testosterone: 3.55 ng/mL and 14.30 pg/mL, respectively. Insulin: 43.3 microU/mL and C peptide: 5.7 ng/mL. The glucose tolerance test demonstrate intolerance to carbohydrates. During operation, the hormone levels in the right ovarian vein were: total and free testosterone of 2.70 ng/mL and 12.70 pg/mL respectively, which normalized after 12 hours of surgery. Other steroid hormones were normal. After six months of surgery the patient had Ferriman score of 10 and eumenorrhea. Weight: 98.100 kg, glucose tolerance test and basal hormone levels were normal. Electron Microscopy showed characteristic data of a steroid producing tumor without crystalloids of Reinke.


In vitro antimicrobial activity of ten medicinal plants against clinical isolates of oral cancer cases.
Suppression of immune system in treated cancer patients may lead to secondary infections that obviate the need of antibiotics. In the present study, an attempt was made to understand the occurrence of secondary infections in immuno-suppressed patients along with herbal control of these infections with the following objectives to: (a) isolate the microbial species from the treated oral cancer patients along with the estimation of absolute neutrophile counts of patients (b) assess the in vitro antimicrobial activity medicinal plants against the above clinical isolates. Blood and oral swab cultures were taken from 40 oral cancer patients undergoing treatment in the radiotherapy unit of Regional Cancer Institute, Pt. B.D.S. Health University,Rohtak, Haryana. Clinical isolates were identified by following general microbiological, staining and biochemical methods. The absolute neutrophile counts were done by following the standard methods. The medicinal plants selected for antimicrobial activity analysis were Asphodelus tenuifolius Cav., Asparagus racemosus Willd., Balanites aegyptiaca L., Cestrum diurnum L., Cordia dichotoma G. Forst, Eclipta alba L., Murraya koenigii (L.) Spreng. , Pedalium murex L., Ricinus communis L. and Trigonella foenum graecum L. The antimicrobial efficacy of medicinal plants was evaluated by modified Kirby-Bauer disc diffusion method. MIC and MFC were investigated by serial two fold microbroth dilution method. Prevalent bacterial pathogens isolated were Staphylococcus aureus (23.2%), Escherichia coli (15.62%), Staphylococcus epidermidis (12.5%), Pseudomonas aeruginosa (9.37%), Klebsiella pneumonia (7.81%), Proteus mirabilis (3.6%), Proteus vulgaris (4.2%) and the fungal pathogens were Candida albicans (14.6%), Aspergillus fumigatus (9.37%). Out of 40 cases, 35 (87.5%) were observed as neutropenic. Eight medicinal plants (A. tenuifolius, A. racemosus, B. aegyptiaca, E. alba, M. koenigii, P. murex R. communis and T. foenum graecum) showed significant antimicrobial activity (P < .05) against most of the isolates. The MIC and MFC values were ranged from 31 to 500 μg/ml. P. aeruginosa was observed highest susceptible bacteria (46.6%) on the basis of susceptible index. It can be concluded that treated oral cancer patients were neutropenic and prone to secondary infection of microbes. The medicinal plant can prove as effective antimicrobial agent to check the secondary infections in treated cancer patients.


For the Benefit of Students: Memory and Anatomical Learning at Bologna in the Fourteenth to Early Sixteenth Centuries.
The anatomical textbook in the late Middle Ages was one part of a greater pedagogical process that involved students' seeing, hearing, reading, and eventually knowing information about the human body. By examining the role of the anatomical textbook and accompanying bodily images in anatomical learning, this article illuminates the complexity and self-consciousness of anatomical education in the medieval university, as professors focused on ways to enhance student memory of the material. Traditionally, the history of anatomy has been heavily influenced by the anatomical Renaissance of the late-sixteenth century, highlighting a focus on innovative medical knowledge and the scientific method. However, if we engage a pedagogical lens when looking at these medieval authors, it becomes quickly obvious that the whole point of university medicine was not to explore unknown boundaries and discover new ideas of medicine, but rather to communicate the current and established body of knowledge to those not familiar with it.


Phycomycosis in a dog.
Chronic vomiting in a 2-year-old dog was suspected to be due to a neoplasm of the stomach wall. During exploratory laparotomy, a lymph node from the pyloric area was examined microscopically. Inasmuch as neoplastic cells or evidence of metastasis were not found, all visibly involved tissue was removed surgically. A diagnosis of phycomycosis was then established by histologic evaluation of the tissue removed. It was concluded that diagnosis of this disease is important inasmuch as it may be treated successfully, in contrast to the situation with malignant neoplastic conditions, which it grossly resembles.


Introduction of a plasmid encoding the OHIO-1 beta-lactamase to an intermediate care ward by patient transfer.
A prospective study of 147 intermediate care ward (ICW) patients for acquisition of gentamicin-resistant Enterobacteriaceae (GRE) was carried out. Fifty (34%) were colonized or infected with one or more strains of GRE. Fifteen of these patients and one nurse were colonized with 22 strains (including ten species) of GRE bearing identical 60 kb plasmids encoding a novel beta-lactamase determinant, OHIO-1 and ANT(2"). Analysis of the time course of colonized patients on the ICW revealed one probable episode of cross-transmission. Five colonized patients had been residing in the ICW from one to four months prior to study initiation. Eight patients were admitted to the ICW from other hospital areas already colonized and one additional patient acquired colonization on the ICW from an unknown source. Thus, eight of ten patients admitted to the ICW during the prospective study were already colonized on admission to the ICW. To control this level of colonization it would therefore be necessary to direct efforts at limiting admission of colonized patients or attempting to eliminate the strain from persistently colonized patients, rather than trying to limit transmission within the ward.


Diaeretiella rapae limits Myzus persicae populations after applications of deltamethrin in oilseed rape.
In fall, Myzus persicae (Sulzer) (Homoptera: Aphididae) may exhibit population resurgence in winter oilseed rape in France. This resurgence may arise from pyrethroid treatments against Coleoptera (Psylliodes chrysocephala L.) that either kill parasitoids present during treatment or prevent recolonization by off-crop parasitoids. We studied the impact of Diaeretiella rapae (M'Intosh) (Hymenoptera: Braconidae) on populations of M. persicae when parasitoids were introduced on deltamethrin-treated plants at increasing intervals after treatment. Parasitoids were introduced 1, 2, 7, or 14 d posttreatment on individually caged plants infested with established populations of M. persicae. Aphids were counted 7, 14 and 21 d after parasitoid introduction. First, we observed that both the pesticide and the parasitoid reduced aphid population growth and that their effects were additive. Second, there was no mortality of parasitoids exposed to treated leaves in a device with a refuge area, and only 20% of mortality without the refuge area. Furthermore, deltamethrin residues had no effect on the reproduction of D. rapae females. Compared with the known toxicity of deltamethrin to D. rapae on glass, this low mortality may have been due to both the high liposolubility of deltamethrin (leading to a rapid diffusion of residues in the oilseed rape leaf cuticle) and to the existence of a refuge area. This work suggests that D. rapae could limit populations of M. persicae in the fall, even after pyrethroid treatment, because the presence of deltamethrin residues had little impact on the parasitoid.


Oncolytic viruses for cancer therapy I. Cell-external factors: virus entry and receptor interaction.
After being recognized for their anti-neoplastic properties at the beginning of the last century, viruses are again being considered for use as therapeutic agents against cancer. Certain virus species have a propensity to replicate within transformed cells, which are commonly rendered vulnerable due to tumor-specific defects in their defense against viral infection. Other viruses have been modified to subject them to tumor-specific growth conditions. Oncolytic viruses carry the promise to efficiently target cancer cells for destruction and spread throughout tumor tissue to reach distant neoplastic loci without causing collateral damage to healthy tissues. In contrast to conventional cancer chemotherapy, viral anti-neoplastic agents require complex interactions with the host organism to reach their target and to unfold their oncolytic activity. Recent progress in the elucidation of the molecular mechanisms of viral pathogenesis has opened up new opportunities to manipulate virus-host interactions, generating effective anti-tumor strategies. On the other hand, significant obstacles towards the application of safe and efficacious viral therapies have become apparent. These frequently relate to the lack of cell culture and animal tumor models that accurately reflect the characteristics of cancerous tissues in patients. Throughout the past century, viral therapeutics against cancer have evolved into a new class of treatment strategies characterized by unique opportunities and challenges. A growing number of oncolytic viruses has entered clinical investigation or is scheduled to do so in the near future. Great efforts are being undertaken to rekindle an old idea and, with the help of new technologies, to realize its promise of new treatment facilities for cancer.


Characterization of the genome of bald cypress.
Bald cypress (Taxodium distichum var. distichum) is a coniferous tree of tremendous ecological and economic importance. It is a member of the family Cupressaceae which also includes cypresses, redwoods, sequoias, thujas, and junipers. While the bald cypress genome is more than three times the size of the human genome, its 1C DNA content is amongst the smallest of any conifer. To learn more about the genome of bald cypress and gain insight into the evolution of Cupressaceae genomes, we performed a Cot analysis and used Cot filtration to study Taxodium DNA. Additionally, we constructed a 6.7 genome-equivalent BAC library that we screened with known Taxodium genes and select repeats. The bald cypress genome is composed of 90% repetitive DNA with most sequences being found in low to mid copy numbers. The most abundant repeats are found in fewer than 25,000 copies per genome. Approximately 7.4% of the genome is single/low-copy DNA (i.e., sequences found in 1 to 5 copies). Sequencing of highly repetitive Cot clones indicates that most Taxodium repeats are highly diverged from previously characterized plant repeat sequences. The bald cypress BAC library consists of 606,336 clones (average insert size of 113 kb) and collectively provides 6.7-fold genome equivalent coverage of the bald cypress genome. Macroarray screening with known genes produced, on average, about 1.5 positive clones per probe per genome-equivalent. Library screening with Cot-1 DNA revealed that approximately 83% of BAC clones contain repetitive sequences iterated 103 to 104 times per genome. The BAC library for bald cypress is the first to be generated for a conifer species outside of the family Pinaceae. The Taxodium BAC library was shown to be useful in gene isolation and genome characterization and should be an important tool in gymnosperm comparative genomics, physical mapping, genome sequencing, and gene/polymorphism discovery. The single/low-copy (SL) component of bald cypress is 4.6 times the size of the Arabidopsis genome. As suggested for other gymnosperms, the large amount of SL DNA in Taxodium is likely the result of divergence among ancient repeat copies and gene/pseudogene duplication.