Contact-haemolysin production by entero-invasive Escherichia coli and shigellae.
Entero-invasive Escherichia coli (EIEC) and shigellae were tested for contact-haemolysin (CH) with red blood cells (RBCs) of guinea-pig, rabbit, rat, mouse, monkey, man, sheep and chicken; all bacteria showed the best lysis with guinea-pig RBCs. The best culture medium for CH activity of shigellae was tryptic soy broth, and for EIEC it was casamino acid-yeast extract broth with 1 mM CaCl2. CH production by all species was best at the slightly alkaline pH which is optimal for growth; it was also dependent on the presence of a large (140-Mda) plasmid. Pre-treatment of bacteria with homologous antisera inhibited CH activity. Various treatments of bacterial cells and RBCs suggested that CH may be a protein molecule, and that a chitotriose-like moiety may serve as CH receptor. RBCs that were incubated with bacteria at 4 degrees C, or with heat-killed bacteria at 37 degrees C, were not lysed; also, isolated cell-surface components (lipopolysaccharide and outer-membrane protein) did not lyse RBCs. This suggests that metabolically active cells are required for CH activity. Production of CH by both EIEC and shigellae is consistent with a common mechanism for the virulence of these organisms.


TgAP2IX-5 is a key transcriptional regulator of the asexual cell cycle division in Toxoplasma gondii.
Apicomplexan parasites have evolved efficient and distinctive strategies for intracellular replication where the timing of emergence of the daughter cells (budding) is a decisive element. However, the molecular mechanisms that provide the proper timing of parasite budding remain unknown. Using Toxoplasma gondii as a model Apicomplexan, we identified a master regulator that controls the timing of the budding process. We show that an ApiAP2 transcription factor, TgAP2IX-5, controls cell cycle events downstream of centrosome duplication. TgAP2IX-5 binds to the promoter of hundreds of genes and controls the activation of the budding-specific cell cycle expression program. TgAP2IX-5 regulates the expression of specific transcription factors that are necessary for the completion of the budding cycle. Moreover, TgAP2IX-5 acts as a limiting factor that ensures that asexual proliferation continues by promoting the inhibition of the differentiation pathway. Therefore, TgAP2IX-5 is a master regulator that controls both cell cycle and developmental pathways.


[European guideline for the quality of non-commercial clinical trials: elegant implementation in the Netherlands via the amended Dutch Medical Research Involving Human Subjects Act].
As of May 2004, the new European directive 2001/20/EC will require European member states to follow Good Clinical Practice rules for non-commercial academic clinical investigations. For several member states this poses a serious threat to such investigations. In the Netherlands however, most items of the new directive can be incorporated in the Dutch Medical Research Involving Human Subjects Act. In fact, many of the items are already covered by this Act, notably with respect to data integrity and patient safety. However, an extra effort is needed to implement the quality control standards to which the registration research already complies. The Dutch Medical Research Involving Human Subjects Act is currently being amended to comply with the new European directive. This is also an ideal opportunity for enhancing the national climate of clinical research and ensuring an improved translation of local research ideas into clinical trial protocols.


Isolation and identification of the first C-17 limonin epimer, epilimonin.
Limonoids are a family of highly oxygenated triterpenoid secondary metabolites found in significant quantities in Citrus and reported to possess multiple health promoting properties. This is the first known report of the isolation and characterization of an epimer of limonin. The epimer, named epilimonin, was isolated by fractional crystallization from a mixture consisting mainly of limonin and epilimonin obtained as byproduct from our efforts to isolate limonin glucoside. Side-by-side comparison of the MS, IR, and (1)H and (13)C NMR data of epilimonin and limonin lead to the assignment of C-17 as the site of epimerization. An earlier study on the bioavailability of limonin glucoside in humans had indicated that limonin glucoside was metabolized to give limonin and a second limonin metabolite. Results from analyzing epilimonin by the same chromatographic conditions used for the bioavailability study suggest that the second limonin metabolite was epilimonin.


Autosomal recessive polycystic kidney disease: the prototype of the hepato-renal fibrocystic diseases.
Autosomal recessive polycystic kidney disease (ARPKD) is a severe, typically early onset form of renal cystic disease. The care of ARPKD patients has traditionally been the purview of pediatric nephrologists for management of systemic hypertension and progressive renal insufficiency. However, the disease has multisystem manifestations and a comprehensive care strategy frequently requires a multidisciplinary team. In severely affected infants, the diagnosis often is first suspected by obstetricians when enlarged, echogenic kidneys and oligohydramnios are detected on prenatal ultrasounds. Neonatologists are central to the care of these infants, who may have respiratory compromise due to pulmonary hypoplasia and massively enlarged kidneys. Among neonatal survivors, a subset of ARPKD patients has clinically significant congenital hepatic fibrosis, which can lead to portal hypertension, requiring close monitoring by pediatric hepatologists. Surgical consultation may be sought to access pre-emptive nephrectomy to relieve mass effect, placement of dialysis access, surgical shunting procedures, and kidney and/or liver transplantation. Recent data suggest that children with ARPKD may be at risk of neurocognitive dysfunction, and may require neuropsychological referral. In addition to these morbidities, families of patients with ARPKD face decisions regarding genetic testing of affected children, testing of asymptomatic siblings, or consideration of preimplantation genetic diagnosis for future pregnancies. These issues require the input of genetic counselors, geneticists, and reproductive endocrinologists. As a result, the management of ARPKD requires the involvement of multiple subspecialists, as well as the general pediatrician, in a complex care network. In this review, we discuss the genetics of this disorder and provide an overview of the associated pathobiology; outline the spectrum of clinical manifestations of ARPKD and the management of organ-specific complications; discuss other disorders that involve genes encoding cilia-associated proteins that can clinically mimic ARPKD; review the animal models available for preclinical studies; and finally, consider future directions for potential targeted therapies.


Phase I trial of dianhydrogalactitol administered Iv in a weekly schedule.
Dianhydrogalactitol was given to 28 patients with a variety of advanced solid tumors on a weekly schedule in iv doses ranging from 2 to 80 mg/m2. No significant toxicity was encountered at doses up to 40 mg/m2/week for 4 weeks. At higher doses mild-to-moderate nausea and vomiting and hematologic toxicity were noted. Thrombocytopenia was more common than granulocytopenia and frequently resolved more slowly. No adverse drug-realted effects on liver, renal, coagulation, or cardiac function were seen. Although no patient had significant antitumor response (as strictly defined), objective improvement was noted in two patients, one with hypernephroma and the other with malignant melanoma. for phase II studies, a weekly dose of 70 mg/m2 is recommended for patients with normal hematopoiesis, with reduction by 25% (55 mg/m2) in patients with extensive prior radiation therapy, prior chemotherapy, and/or widespread metastasis to the bone.


The effects of the endotracheal tube suctioning/manual hyperventilation procedure on patients with severe closed head injuries.
The findings of this clinical study suggest that the ETTS/MH procedure could be safely performed upon patients with severe closed head injuries whose baseline measurements of MICP were within the range of 0 to 20 mm Hg, provided the CPP was maintained at 50 mm Hg or greater. The advantages of performing the ETTS/MH procedure upon intubated patients far outweigh the possible disadvantages. The removal of pulmonary mucus plugs and secretions, which subsequently prevents hypercarbia and hypoxemia, is very important to the patient's recovery. In most situations, stimulation of the cough reflex through ETTS or even MH can help prevent atelectasis, a frequent pulmonary complication of neurologically depressed patients. Atelectasis can result in hypoxia that may adversely affect the cerebrovascular status. In addition, the results of this study suggest that multiple MHs after the third and subsequent ETTSs should be extended to a longer time interval, perhaps 60 seconds, in order that the physiologic measurements of MABP, MICP, CPP, and HR more closely approach the baseline levels. Also it is suggested that nurses performing the ETTS/MH procedure delay initiation of levels of physiologic function used to assess cerebrovascular status are reached.


Metachromatic leukodystrophy - mutation analysis provides further evidence of genotype-phenotype correlation.
Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disorder resulting from the inherited deficiency of the arylsulfatase A (ARSA) enzyme. Currently, no valid therapeutic options are available for affected patients. A thorough knowledge of disease progression in its diverse clinical variants, together with the identification of reliable prognostic factors, could be instrumental in accurate patient selection for new upcoming therapeutic opportunities, such as enzyme replacement and gene therapy. The described correlation between genotype and clinical presentation proved helpful in predicting patient's prognosis, only in the minority of MLD patients harboring common mutations. Molecular characterization of a cohort of 26 MLD patients allowed us to identify 18 mutations, excluding the common 0 and R alleles, 10 of which are rare and 8 are novel. By categorizing the rare mutations, we were able to confirm a correlation between ARSA gene mutations, age at onset and patterns of disease progression, not only in those patients bearing common mutations, but also in those carrying rare mutant alleles. Moreover, in the case of absent or delayed molecular diagnosis, or of newly identified mutations, the involvement of peripheral nervous system from disease onset proved to be a sensitive prognostic marker predicting a severe progression.


Recurrent visceral leishmaniasis in an immunocompetent patient: a case report.
Current treatment options for visceral leishmaniasis (pentavalent antimony, amphotericin B, liposomal amphotericin B and mitelfosine) achieve long-term clinical cure in the majority of immunocompetent patients. Disease relapse is usually provoked by T-cell number or function impairment (corticosteroid or cytotoxic therapy, transplant recipients, advanced human immunodeficiency virus disease). We report a case of visceral leishmaniasis with multiple relapses in a 75-year-old Greek immunocompetent man. Visceral leishmaniasis relapses occurred despite appropriate treatment with liposomal amphotericin B 3mg/kg/day on days one to five, 14 and 21 (for the first episode and the first relapse) and mitelfosine 150mg/day for 28 days (for the second relapse). The third relapse was treated with high-dose liposomal amphotericin B (10mg/kg for two consecutive days), followed by a secondary prophylaxis of 3mg/kg once per month, which prevented disease reappearance during one year of follow-up. An unusual case of recurrent visceral leishmaniasis in an older immunocompetent patient was treated with high-dose liposomal amphotericin B and a monthly prophylaxis with no evidence of a relapse after one year of follow-up.


Sex choice in plants: facultative adjustment of the sex ratio in the perennial herb Begonia gracilis.
Sex allocation theory predicts that reproducing individuals will increase their fitness by facultatively adjusting their relative investment towards the rarer sex in response to population shifts in operational sex ratio (OSR). The evolution of facultative manipulation of sex ratio depends on the ability of the parents to track the conditions favouring skewed sex allocation and on the mechanism controlling sex allocation. In animals, which have well-developed sensorial mechanisms, facultative adjustment of sex ratios has been demonstrated on many occasions. In this paper, we show that plants have mechanisms that allow them to evaluate the population OSR. We simulated three different conditions of population OSR by manipulating the amount of pollen received by the female flowers of a monoecious herb, and examined the effect of this treatment on the allocation to male vs. female flowers. A shortage of pollen on the stigmas resulted in a more male-skewed sex allocation, whereas plants that experienced a relatively pollen rich environment tended to produce a more female-skewed sex allocation pattern. Our results for Begonia gracilis demonstrate that the individuals of this species are able to respond to the levels of pollination intensity experienced by their female flowers and adjust their patterns of sex allocation in accordance to the expectations of sex allocation theory.


Nitric oxide regulation of mitochondrial oxygen consumption I: cellular physiology.
Mitochondrial biochemistry is complex, expanding from oxygen consumption, oxidative phosphorylation, lipid catabolism, heme biosynthesis, to apoptosis, calcium homeostasis, and production of reactive oxygen species, including nitric oxide (NO). The latter molecule is produced by a mitochondrial NO synthase (mtNOS). The rates of consumption and production determine the steady-state concentration of NO at subcellular levels, leading to regulation of mitochondrial events. Temporospatial processes tightly regulate production of NO in mitochondria to maximize target effects and minimize deleterious reactions. Temporal regulatory mechanisms of mtNOS include activation by calcium signaling and transcriptional/translational regulations. Calcium-activated mtNOS inhibits mitochondrial respiration, resulting in a decrease of the oxygen consumption. This negative regulation antagonizes the effects of calcium on calcium-dependent dehydrogenases in the citric acid cycle, preventing the formation of anoxic foci. Temporal regulation of NO production by intracellular calcium signaling is a complex process, considering the heterogeneous intracellular calcium response and distribution. NO production in mitochondria is spatially regulated by mechanisms that determine subcellular localization of mtNOS, likely acylation and protein-protein interactions, in addition to transcriptional regulation as neuronal NOS. Because NO rapidly decays in mitochondria, subcellular localization of mtNOS is crucial for NO to function as a signal molecule. These temporospatial processes are biologically important to allow NO to act as an effective signal molecule to regulate mitochondrial events such as oxygen consumption and reactive oxygen species production.


Phase separation of intrinsically disordered FG-Nups is driven by highly dynamic FG motifs.
The intrinsically disordered FG-Nups in the central channel of the nuclear pore complex (NPC) form a selective permeability barrier, allowing small molecules to traverse by passive diffusion, while large molecules can only translocate with the help of nuclear transport receptors. The exact phase state of the permeability barrier remains elusive. In vitro experiments have shown that some FG-Nups can undergo phase separation into condensates that display NPC-like permeability barrier properties. Here, we use molecular dynamics simulations at amino acid resolution to study the phase separation characteristics of each of the disordered FG-Nups of the yeast NPC. We find that GLFG-Nups undergo phase separation and reveal that the FG motifs act as highly dynamic hydrophobic stickers that are essential for the formation of FG-Nup condensates featuring droplet-spanning percolated networks. Additionally, we study phase separation in an FG-Nup mixture that resembles the NPC stoichiometry and observe that an NPC condensate is formed containing multiple GLFG-Nups. We find that the phase separation of this NPC condensate is also driven by FG-FG interactions, similar to the homotypic FG-Nup condensates. Based on the observed phase separation behavior, the different FG-Nups of the yeast NPC can be divided into two classes: The FG-Nups (mostly GLFG-type) located in the central channel of the NPC form a highly dynamic percolated network formed by many short-lived FG-FG interactions, while the peripheral FG-Nups (mostly FxFG-type) at the entry and exit of the NPC channel likely form an entropic brush.


Circleator: flexible circular visualization of genome-associated data with BioPerl and SVG.
Circleator is a Perl application that generates circular figures of genome-associated data. It leverages BioPerl to support standard annotation and sequence file formats and produces publication-quality SVG output. It is designed to be both flexible and easy to use. It includes a library of circular track types and predefined configuration files for common use-cases, including. (i) visualizing gene annotation and DNA sequence data from a GenBank flat file, (ii) displaying patterns of gene conservation in related microbial strains, (iii) showing Single Nucleotide Polymorphisms (SNPs) and indels relative to a reference genome and gene set and (iv) viewing RNA-Seq plots. Circleator is freely available under the Artistic License 2.0 from http://jonathancrabtree.github.io/Circleator/ and is integrated with the CloVR cloud-based sequence analysis Virtual Machine (VM), which can be downloaded from http://clovr.org or run on Amazon EC2.


Identification of astroglia-like cardiac nexus glia that are critical regulators of cardiac development and function.
Glial cells are essential for functionality of the nervous system. Growing evidence underscores the importance of astrocytes; however, analogous astroglia in peripheral organs are poorly understood. Using confocal time-lapse imaging, fate mapping, and mutant genesis in a zebrafish model, we identify a neural crest-derived glial cell, termed nexus glia, which utilizes Meteorin signaling via Jak/Stat3 to drive differentiation and regulate heart rate and rhythm. Nexus glia are labeled with gfap, glast, and glutamine synthetase, markers that typically denote astroglia cells. Further, analysis of single-cell sequencing datasets of human and murine hearts across ages reveals astrocyte-like cells, which we confirm through a multispecies approach. We show that cardiac nexus glia at the outflow tract are critical regulators of both the sympathetic and parasympathetic system. These data establish the crucial role of glia on cardiac homeostasis and provide a description of nexus glia in the PNS.


Improving Sensitivity of the Digits-In-Noise Test Using Antiphasic Stimuli.
The digits-in-noise test (DIN) has become increasingly popular as a consumer-based method to screen for hearing loss. Current versions of all DINs either test ears monaurally or present identical stimuli binaurally (i.e., diotic noise and speech, NoSo). Unfortunately, presentation of identical stimuli to each ear inhibits detection of unilateral sensorineural hearing loss (SNHL), and neither diotic nor monaural presentation sensitively detects conductive hearing loss (CHL). After an earlier finding of enhanced sensitivity in normally hearing listeners, this study tested the hypothesis that interaural antiphasic digit presentation (NoSπ) would improve sensitivity to hearing loss caused by unilateral or asymmetric SNHL, symmetric SNHL, or CHL. This cross-sectional study recruited adults (18 to 84 years) with various levels of hearing based on a 4-frequency pure-tone average (PTA) at 0.5, 1, 2, and 4 kHz. The study sample was comprised of listeners with normal hearing (n = 41; PTA ≤ 25 dB HL in both ears), symmetric SNHL (n = 57; PTA > 25 dB HL), unilateral or asymmetric SNHL (n = 24; PTA > 25 dB HL in the poorer ear), and CHL (n = 23; PTA > 25 dB HL and PTA air-bone gap ≥ 20 dB HL in the poorer ear). Antiphasic and diotic speech reception thresholds (SRTs) were compared using a repeated-measures design. Antiphasic DIN was significantly more sensitive to all three forms of hearing loss than the diotic DIN. SRT test-retest reliability was high for all tests (intraclass correlation coefficient r > 0.89). Area under the receiver operating characteristics curve for detection of hearing loss (>25 dB HL) was higher for antiphasic DIN (0.94) than for diotic DIN (0.77) presentation. After correcting for age, PTA of listeners with normal hearing or symmetric SNHL was more strongly correlated with antiphasic (rpartial[96] = 0.69) than diotic (rpartial = 0.54) SRTs. Slope of fitted regression lines predicting SRT from PTA was significantly steeper for antiphasic than diotic DIN. For listeners with normal hearing or CHL, antiphasic SRTs were more strongly correlated with PTA (rpartial[62] = 0.92) than diotic SRTs (rpartial[62] = 0.64). Slope of the regression line with PTA was also significantly steeper for antiphasic than diotic DIN. The severity of asymmetric hearing loss (poorer ear PTA) was unrelated to SRT. No effect of self-reported English competence on either antiphasic or diotic DIN among the mixed first-language participants was observed. Antiphasic digit presentation markedly improved the sensitivity of the DIN test to detect SNHL, either symmetric or asymmetric, while keeping test duration to a minimum by testing binaurally. In addition, the antiphasic DIN was able to detect CHL, a shortcoming of previous monaural or binaurally diotic DIN versions. The antiphasic DIN is thus a powerful tool for population-based screening. This enhanced functionality combined with smartphone delivery could make the antiphasic DIN suitable as a primary screen that is accessible to a large global audience.


Management of common potentially serious paediatric illnesses by aid post orderlies at Tari, Southern Highlands Province.
Systematic observations were made of a small number of aid post orderlies (APOs) managing children with the common but potentially serious symptoms of cough, fever and diarrhoea. On-site performance was evaluated against recommended management guidelines set out in Dr Keith Edwards' Diagnosis and Treatment of Common Childhood Illnesses for APOs. History taking at the aid post was brief and usually non-exploratory; examination of patients was often neglected. Drug prescription was generally appropriate for the diagnosis made, but drug dosages were often incorrect and treatment principles were rarely explained to guardians. Preventive health issues were rarely tackled. Our study reaffirms the need for on-site assessment of the performance of paramedical workers, sets priority demands for continuing education of health workers, and provides a framework for competency-based problem-solving activities within this context.


A Novel R2R3-MYB Transcription Factor FaMYB10-like Promotes Light-Induced Anthocyanin Accumulation in Cultivated Strawberry.
Anthocyanins widely accumulate in the vegetative and reproductive tissues of strawberries and play an important role in stress resistance and fruit quality. Compared with other fruits, little is known about the molecular mechanisms regulating anthocyanin accumulation in strawberry vegetative tissues. In this study, we revealed an R2R3-MYB transcription factor, FaMYB10-like (FaMYB10L), which positively regulated anthocyanin accumulation and was induced by light in the petiole and runner of cultivated strawberry. FaMYB10L is a homologue of FveMYB10-like and a nuclear localization protein. Transient overexpression of FaMYB10L in a white fruit strawberry variety (myb10 mutant) rescued fruit pigmentation, and further qR-PCR analysis revealed that FaMYB10L upregulated the expression levels of anthocyanin biosynthesis-related genes and transport gene. A dual luciferase assay showed that FaMYB10L could activate the anthocyanin transport gene FaRAP. Anthocyanin accumulation was observed in FaMYB10L-overexpressing strawberry calli, and light treatment enhanced anthocyanin accumulation. Furthermore, transcriptomic profiling indicated that the DEGs involved in the flavonoid biosynthesis pathway and induced by light were enriched in FaMYB10L-overexpressing strawberry calli. In addition, yeast two-hybrid assays and luciferase complementation assays indicated that FaMYB10L could interact with bHLH3. These findings enriched the light-involved regulatory network of anthocyanin metabolism in cultivated strawberries.


Eye protection for the surgeon.
The surgeon today is obliged to operate on an increasing number of patients who are classed as high risk. A study is presented which examines the extent of potential corneal contamination with blood or tissue fluids, during common orthopaedic operations. In all, 65% of goggles worn by surgeons during the study were contaminated. The greatest risk was associated with operations around the hip joint, which are among the commonest orthopaedic procedures. Increased contamination was associated with the use of power tools and irrigation. The contamination rate of the protective flaps at the side of the goggles was relatively low (5%) suggesting that ordinary spectacles, which are more convenient and comfortable than the standard issue goggles, would provide adequate protection during routine use.


Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia.
Early allogeneic hematopoietic stem cell transplantation (HSCT) has been proposed as primary treatment modality for patients with chronic myeloid leukemia (CML). This concept has been challenged by transplantation mortality and improved drug therapy. In a randomized study, primary HSCT and best available drug treatment (IFN based) were compared in newly diagnosed chronic phase CML patients. Assignment to treatment strategy was by genetic randomization according to availability of a matched related donor. Evaluation followed the intention-to-treat principle. Six hundred and twenty one patients with chronic phase CML were stratified for eligibility for HSCT. Three hundred and fifty four patients (62% male; median age, 40 years; range, 11-59 years) were eligible and randomized. One hundred and thirty five patients (38%) had a matched related donor, of whom 123 (91%) received a transplant within a median of 10 months (range, 2-106 months) from diagnosis. Two hundred and nineteen patients (62%) had no related donor and received best available drug treatment. With an observation time up to 11.2 years (median, 8.9 years), survival was superior for patients with drug treatment (P = .049), superiority being most pronounced in low-risk patients (P = .032). The general recommendation of HSCT as first-line treatment option in chronic phase CML can no longer be maintained. It should be replaced by a trial with modern drug treatment first.


Cell Wall Polysaccharides of Candida albicans Induce Mast Cell Degranulation in the Gut.
We investigated Candida albicans-induced mast cell degranulation in vitro and in vivo. Cell wall fraction but not culture supernatant and cell membrane fraction prepared from hyphally grown C. albicans induced β-hexosaminidase release in RBL-2H3 cells. Cell wall mannan and soluble β-glucan fractions also induced β-hexosaminidase release. Histological examination of mouse forestomach showed that C. albicans gut colonization induces mast cell degranulation. However, intragastric administration of cell wall fraction failed to induce mast cell degranulation. We propose that cell wall polysaccharides are responsible for mast cell degranulation in the C. albicans-colonized gut.


Phylogenetic analysis of new Prasinoviruses (Phycodnaviridae) that infect the green unicellular algae Ostreococcus, Bathycoccus and Micromonas.
Viruses play an important role in the regulation of phytoplankton populations. In the Mediterranean Sea, prasinophyte green algae are abundant and widespread, and within this group the genera Bathycoccus, Micromonas and Ostreococcus (Mamiellales) are the most common. Although these organisms constitute a significant part of the marine ecosystem, little is known about the viruses infecting them. We showed that double-stranded DNA viruses, likely members of the Phycodnaviridae family, can infect and grow in different host laboratory prasinophyte strains. Different pairs of degenerate primers were designed to PCR amplify a region of the conserved viral polymerase gene in order to characterize these viral strains. Twenty-seven new viral strains from five different host strains were thus analysed. We established phylogenetic trees for the hosts (18S) and their associated viruses (partial polymerase gene) and discuss the taxonomic significance of Phycodnaviridae. Within eukaryotic double-stranded DNA viruses, we showed that viruses from Bathycoccus, Micromonas and Ostreococcus form a monophyletic group that we refer to as 'Prasinovirus'.


Scheimpflug image-based changes in anterior segment parameters during accommodation induced by short-term reading.
To analyze the effect of the accommodation on the anterior segment data (corneal and anterior chamber parameters) induced by short-time reading in a healthy, nonpresbyopic adult patient group. Images of both eyes of nonpresbyopic volunteers were captured with a Scheimpflug device (Pentacam HR) in a nonaccommodative state. Fifteen minutes of reading followed and through fixation of the built-in target of Pentacam HR further accommodation was achieved and new images were captured by the device. Anterior segment parameters were observed and the differences were analyzed. Fifty-two healthy eyes of 26 subjects (range 20.04-28.58 years) were analyzed. No significant differences were observed in the keratometric values before and after the accommodative task (p = 0.35). A statistically significant difference was measured in the 5.0-mm-diameter and the 7.0-mm-diameter corneal volume (p = 0.01 and p = 0.03) between accommodation states. Corneal aberrometric data did not change significantly during short-term accommodation. Significant differences were observed between nonaccommodative and accommodative states of the eyes for all measured anterior chamber parameters. Among the parameters of the cornea, only corneal volume changed during the short-term accommodation process, showing some fine changes with accommodation of the cornea in young, emmetropic patients. The position of the pupil and the anterior chamber parameters were observed to change with accommodation as captured by a Scheimpflug device.


Epitope conservation and immunohistochemical localization of the guanylin/stable toxin peptide receptor, guanylyl cyclase C.
The heat-stable enterotoxins (ST) are a family of cysteine-rich low-molecular weight peptides produced by pathogenic bacteria, and are one of the major causes of watery diarrhea all over the world. These toxins mediate their action by binding to an intestinal cell surface receptor that is a membrane-associated guanylyl cyclase (GCC). This receptor also serves as the receptor for the recently characterised endogenous ligand, guanylin. We have expressed various domains of the receptor in Escherichia coli and used purified proteins for the generation of both polyclonal and monoclonal antibodies. While polyclonal antibodies were able to partially inhibit ST binding to the native receptor present in the T84 human colonic cell line, GCC:B10 monoclonal antibody did not interfere with ligand binding. Western blot analysis, using membranes prepared from human colonic T84 cells, detected two bands of size 160 and 140 kDa, representing alternately glycosylated forms of the receptor. Using the recombinant proteins, we could map the epitope of GCC:B10 monoclonal antibody to the intracellular domain of the receptor. We used the antibody to localize the receptor throughout the rat intestine, and in the porcine and bonnet monkey colon. We could detect receptor expression in the villus and the crypts of the duodenum, jejunum, ileum, and caecum, and in the crypts of the colon. Receptor expression was observed in cells that had earlier been shown to express cGMP-dependent kinase, but not the cystic fibrosis transmembrane regulator, a known downstream target of cGMP/G-kinase, which suggests that GCC/ cGMP could regulate additional cellular signal transduction machinery.


Controlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing.
DNA damage has been implicated in ageing, but direct evidence for a causal relationship is lacking, owing to the difficulty of inducing defined DNA lesions in cells and tissues without simultaneously damaging other biomolecules and cellular structures. Here we directly test whether highly toxic DNA double-strand breaks (DSBs) alone can drive an ageing phenotype using an adenovirus-based system based on tetracycline-controlled expression of the SacI restriction enzyme. We deliver the adenovirus to mice and compare molecular and cellular end points in the liver with normally aged animals. Treated, 3-month-old mice display many, but not all signs of normal liver ageing as early as 1 month after treatment, including ageing pathologies, markers of senescence, fused mitochondria and alterations in gene expression profiles. These results, showing that DSBs alone can cause distinct ageing phenotypes in mouse liver, provide new insights in the role of DNA damage as a driver of tissue ageing.


Asthma and COVID-19; different entities, same outcome: a meta-analysis of 107,983 patients.
There are varying reports of the prevalence and effect of comorbid asthma in coronavirus disease-2019 (COVID-19) patients. We sought to conduct a meta-analysis comparing asthmatic and non-asthmatic patients to determine the clinical significance of preexisting asthma in COVID-19 patients. Online databases PubMed, ScienceDirect, Web of Science, and Scopus, were searched up to July 15, 2020, for papers comparing asthma versus non-asthma COVID-19 patients. According to prespecified inclusion criteria, this analysis included eleven retrospective studies with 107,983 COVID-19 patients. Subgroup analysis was performed based on age groups. The mean age of the patients was 59.9 years (95%CI = 51.9-67.9). Across studies, the prevalence of asthma was 11.2% (95%CI: 9.1%-13.3%) among COVID-19 patients who attended the hospitals. Asthma patients were more likely to be younger (SMD = -0.36, 95%CI = -0.61 to -0.10, p = 0.005), and obese (OR = 1.98, 95%CI = 1.54-2.55, p < 0.001), there was no differential risk of hospitalization rate, ICU admission, or development of acute respiratory distress syndrome (ARDS) between asthmatic and non-asthmatic cohorts. However, asthmatic patients had increased risk of endotracheal intubation (RR = 1.27, 95%CI = 1.02-1.58, p = 0.030) especially patients aged <50 years (RR = 6.68, 95%CI = 1.76-11.13, p = 0.009). Despite this result, asthmatic patients had better recovery with a higher liability of being discharged and were less likely to die (RR = 0.80, 95%CI = 0.65-0.97, p = 0.026). To our knowledge, our meta-analysis is the largest to shed light on preexisting asthma as a predictor of intubation in COVID-19, especially in young and obese patients. Identifying high-risk groups is crucial for designing more effective intervention plans and optimization of efficient resource allocation.


Diet and lung cancer risk from a 14-year population-based prospective study in Japan: with special reference to fish consumption.
N-3 polyunsaturated fatty acids in fish oil exhibit a variety of health benefits, and there is evidence that they can inhibit the development of human lung mucoepidermoid and other carcinomas. To examine the hypothesis that fish consumption reduces the risk of lung cancer, we conducted a population-based prospective study, following 5,885 residents for 14 yr. Person-years were used to calculate the relative risk (RR) by the Cox proportional hazards model, with adjustment for potential confounding factors. A total of 51 incident lung cancer cases were observed, and we found linearly decreasing RRs for lung cancer with increased frequency of consumption of fish and shellfish (RRs = 1.00, 0.99, and 0.32, P for trend = 0.003) but not with intake of dried/salted fish. Decreased RRs were apparent with both broiling and boiling cooking methods, but reduction with raw and deep-fried fish consumption was not statistically significant. We conclude that frequent fresh fish consumption, irrespective of the cooking method, may reduce the risk of lung cancer.


Trace elements in blood samples of smoker and nonsmoker active pulmonary tuberculosis patients from Jamshoro, Pakistan.
Pulmonary tuberculosis (PTB) is a serious public threat throughout the world. PTB and smoking have a strong correlation. Malnutrition, poverty, addiction, overcrowding, illiteracy, unemployment, and poor hygienic conditions are the collective aspects for the disease progress. Pakistan is the fifth among 22 high tuberculosis (TB) burden countries and the fourth regarding multidrug-resistant tuberculosis (MDR-TB). The aim of study was to determine the concentration of essential and toxic elements from blood samples of smoker and nonsmoker PTB patients by inductively coupled plasma mass spectrometry (ICP-MS) followed by microwave acid digestion and compared with control subjects (n = 30). Eighty PTB patients were selected from different hospitals with age ranging 20-70 years. It was interpreted that the mean age among males and females was found to be 35.6 ± 1.4 and 33.5 ± 1.2, respectively, and the male patients were highly affected in contrast to females. Essential elements such as Mn, Fe, Zn, and Se were statistically found to be lower while Ca, Co, and Cu were found to be higher compared to the control group (p = 0.00). However, toxic elements like Al, Cr, Ni, As, Cd, and Pb were statistically elevated in smokers than nonsmokers. Further research is needed to understand the degree of the impact of essential trace elements on treatment outcome (follow-up) followed by balanced healthy nutritional supplementation along with medical therapy, consequently improving the pulmonary tuberculosis outcome and survival as well.


Reliability, validity, and clinical utility of the Executive Function Performance Test: a measure of executive function in a sample of people with stroke.
This study examined the reliability and validity of the Executive Function Performance Test (EFPT). The EFPT assesses executive function deficits in the performance of real-world tasks. It uses a structured cueing and scoring system to assess higher-level cognitive functions, specifically initiation, organization, sequencing safety and judgment, and task completion. Seventy-three participants with mild to moderate stroke and 22 age- and education-matched controls completed the 4 EFPT tasks (cooking, using the telephone, managing medications, and paying bills). Significant differences were found between participants with mild and moderate stroke and healthy control participants. The EFPT can help occupational therapists determine the level of support needed by people with cognitive impairments to perform complex instrumental tasks. Objective information derived from this assessment is an essential part of the process of determining whether the person can live independently and helping families understand how to support the performance of their family members at home.


Label-Free Virtual HER2 Immunohistochemical Staining of Breast Tissue using Deep Learning.
The immunohistochemical (IHC) staining of the human epidermal growth factor receptor 2 (HER2) biomarker is widely practiced in breast tissue analysis, preclinical studies, and diagnostic decisions, guiding cancer treatment and investigation of pathogenesis. HER2 staining demands laborious tissue treatment and chemical processing performed by a histotechnologist, which typically takes one day to prepare in a laboratory, increasing analysis time and associated costs. Here, we describe a deep learning-based virtual HER2 IHC staining method using a conditional generative adversarial network that is trained to rapidly transform autofluorescence microscopic images of unlabeled/label-free breast tissue sections into bright-field equivalent microscopic images, matching the standard HER2 IHC staining that is chemically performed on the same tissue sections. The efficacy of this virtual HER2 staining framework was demonstrated by quantitative analysis, in which three board-certified breast pathologists blindly graded the HER2 scores of virtually stained and immunohistochemically stained HER2 whole slide images (WSIs) to reveal that the HER2 scores determined by inspecting virtual IHC images are as accurate as their immunohistochemically stained counterparts. A second quantitative blinded study performed by the same diagnosticians further revealed that the virtually stained HER2 images exhibit a comparable staining quality in the level of nuclear detail, membrane clearness, and absence of staining artifacts with respect to their immunohistochemically stained counterparts. This virtual HER2 staining framework bypasses the costly, laborious, and time-consuming IHC staining procedures in laboratory and can be extended to other types of biomarkers to accelerate the IHC tissue staining used in life sciences and biomedical workflow.


A controlled trial of revascularization in acute stroke.
To compare safety and utility of intraarterial revascularization with use of stents to no revascularization in patients who either failed to respond to intravenous thrombolysis (IVT) or have contraindications to IVT. The case-control study was approved by local ethics committees; all patients signed informed consent. One hundred thirty-one patients (74 men; mean age, 65.9 years ± 12.3; range, 25-86 years) with acute ischemic stroke (AIS) due to middle cerebral artery (MCA) occlusion were enrolled; 75 underwent IVT. No further recanalization therapy was performed in 26 (35%) IVT-treated patients with MCA recanalization (group 1). Patients with IVT failure after 60 minutes were allocated to endovascular treatment (group 2A) or no further therapy (group 2B). Patients with contraindication to IVT were allocated to endovascular treatment within 8 hours since AIS onset (group 3A) or to no recanalization therapy (group 3B). Neurologic deficit at admission, MCA recanalization, symptomatic intracerebral hemorrhage (SICH), and 3-month clinical outcome were evaluated. Favorable clinical outcome was defined as modified Rankin scale score 0-2 at 3 months after stroke onset. Two-sided Mann-Whitney U test, independent samples t test, Fisher exact test, multivariate logistic regression analysis of baseline variables, and complete MCA recanalization for the prediction of favorable clinical outcome were used for statistical evaluation. Median National Institutes of Health Stroke Scale score at admission was 13.5, 16.0, 15.5, 15.0, and 16.0 in groups 1, 2A, 2B, 3A, and 3B, respectively (P > .05); SICH occurred in one of 26 (3.8%), one of 23 (4.3%), one of 26 (3.8%), one of 31 (3.2%), and one of 25 (4.0%) patients, respectively (P > .05). MCA recanalization after endovascular treatment was achieved in 50 of 54 (92.6%) patients. Favorable outcome was significantly different between groups 2A and 2B (10 of 23 [43.5%] and four of 26 [15.4%], respectively; P = .03) and groups 3A and 3B (14 of 31 [45.2%] and two of 25 [8.0%], respectively; P = .004) and was dependent on MCA recanalization (odds ratio, 5.55; P = .006). In this controlled trial, intraarterial revascularization with stents was an effective and safe-effective treatment option in patients with acute MCA occlusion with contraindication to IVT or after IVT failure.


Epidemiology of brachial plexus injuries in a multitrauma population.
The purpose was to identify the prevalence, causative factors, injury types, and associated injury patterns in multitrauma patients who sustained brachial plexus injuries. A retrospective review of a prospectively collected and computerized database and a chart review were performed. Brachial plexus injuries were identified in 54 of 4538 (1.2%) patients presenting to a regional trauma facility. Young male patients predominated. Motor vehicle accidents were the most frequent cause overall, but only 0.67% of such accidents resulted in plexus injuries. Conversely, 4.2% of motorcycle accident victims and 4.8% of snowmobile accident victims suffered brachial plexus injuries. Injuries were supraclavicular for 62% of patients and infraclavicular for 38%. Supraclavicular injuries were more likely to be severe (Sunderland Grade 3 or 4), compared with infraclavicular injuries, which were neurapraxic in 50% of cases (P < 0.01). The former therefore required surgical exploration and reconstruction more often (52 versus 17%; P < 0.05). Associated injuries included closed head injuries with loss of consciousness in 72% of patients (coma in 19%), cervical spine fractures in 13%, and clavicle, scapular, or humeral fractures and shoulder dislocations or sprains in 15 to 22%. Rib fractures were observed in 41% and were complicated by internal thoracic injuries in a similar percentage of cases. The injury severity score ranged from 5 to 59, with a mean of 24, and two patients died. Brachial plexus injuries afflict slightly more than 1% of multitrauma victims. Motorcycle and snowmobile accidents carry especially high risks, with the incidence of injury approaching 5%. Head injuries, thoracic injuries, and fractures and dislocations affecting the shoulder girdle and cervical spine are particularly common associated injuries. Supraclavicular injuries are more common, are of more severe grade, more often require surgery, and are associated with worse prognosis, compared with infraclavicular injuries.


Neuroimaging tools to rate regional atrophy, subcortical cerebrovascular disease, and regional cerebral blood flow and metabolism: consensus paper of the EADC.
Neuroimaging is a mainstay in the differential diagnosis of patients with cognitive impairment. The often equivocal clinical pictures, the prognostic uncertainty of the earliest stages of mild cognitive impairment, and the subtle brain changes mean that neuroimaging techniques are of potentially great incremental diagnostic value. A number of methods, ranging from very simple subjective visual ratings to highly sophisticated computerised tools, have been developed, which allow rating of structural and functional brain changes. The choice of the method is not obvious, and current guidelines provide no indications on which tools should be preferred. In this paper, we give indications for tools with demonstrated accuracy for detecting regional atrophy, cerebrovascular disease, and regional brain function, and discuss these according to increasing technological complexity, ranging from those with high feasibility that can be used at the patient's bedside to highly technological ones that require trained personnel and specific hardware and software.


Pregnancy associated brucellosis.
Brucellosis zoonotic infection caused by Brucella spp. In endemic countries, the disease does not spare the pregnant. There is evidence that brucellosis can induce abortion in humans. Positive cultures of brucella from human placenta, aborted fetuses, and other products of conception were reported previously. It is speculated that brucellosis causes fewer spontaneous abortions in humans than animals due to the absence of Erythritol in the human placenta and fetus. In addition, the presence of anti-brucella activity in human amniotic fluid may also play a role. Rifampin is considered the mainstay of treatment of brucellosis during pregnancy, in various combinations. In a retrospective study of brucellosis in pregnancy, antepartum treatment with antimicrobial agents was more protective against the occurrence of abortion than no or inadequate treatment. It seems that the incidence of abortion is not different among patients treated with either trimethoprim-sulfamethoxazole with or without rifampicin. With therapy during pregnancy, the overall success rate resulting in normal delivery is 90%. The article discussed few of the patents associated with brucellosis.


Repeatability of vessel density measurements of optical coherence tomography angiography in normal and glaucoma eyes.
To compare the intrasession repeatability of peripapillary and macular vessel density measurements of optical coherence tomography angiography (OCTA) in normal and glaucoma eyes, and to evaluate the effect of signal strength of OCTA scans on the repeatability. In a cross-sectional study, three optic nerve head scans each of 65 eyes (30 normal, 35 glaucoma eyes) and three macular scans each of 69 eyes (35 normal, 34 glaucoma eyes) acquired in the same session with OCTA were analysed. Repeatability was assessed using within-subject coefficient of repeatability (CRw) and variation (CVw). Effect of signal strength index (SSI) on repeatability was evaluated with repeated-measures mixed-effects models. CRw (%) and CVw (%) of peripapillary measurements in normal eyes ranged between 3.3 and 7.0, and 2.5 and 4.4 respectively, and that in glaucoma eyes between 3.5 and 7.1, and 2.6 and 6.6. For the macular, these measurements ranged between 4.1 and 6.0, and 3.3 and 4.7 in normal eyes and 4.3 and 6.9, and 3.7 and 5.6 in glaucoma eyes. Repeatability estimates of most measurements were similar in normal and glaucoma eyes. Vessel densities of both peripapillary and macular regions significantly increased with increase in SSI of repeat scans (coefficients ranging from 0.15 to 0.38, p<0.01 for all associations). Repeatability estimates of OCTA measured peripapillary and macular vessel densities were similar in normal eyes and eyes with glaucoma. SSI values of the scans had a significant effect on the repeatability of OCTA with the vessel density values increasing in scans with higher SSI values.


Measuring the effects of the new ECOWAS and WAEMU tobacco excise tax directives.
In December 2017, the 15-member ECOWAS (Economic Community of West African States) and the 8-member WAEMU (West African Economic and Monetary Union, a subset of ECOWAS) passed new Tobacco Tax Directives. Both Directives increased the minimum ad valorem excise tax rate to 50%. In addition the ECOWAS Directive introduced a minimum specific tax (US$ 0.02/stick), but the WAEMU Directive did not. This paper examines the likely effects of these new Directives on cigarette prices, sales volumes and revenues. Tax simulation models using comparable data were constructed for each of the 15 countries to estimate the effects of the ECOWAS and WAEMU Directives. If the 15 ECOWAS members implement the ECOWAS Directive it would substantially increase the retail price of cigarettes (unweighted average 51%, range: 12% to 108%), decrease sales volumes (22%, range: -8% to -39%) and increase tax revenue (373%, range: 10% to 1243%). The impact of the WAEMU Directive on WAEMU countries' cigarette prices (unweighted average +2%), sales volumes (-1%) and revenue (+17%) is likely to be minimal. The 2017 ECOWAS Directive, which adds a specific excise tax per pack, along with an increase in the ad valorem tax, substantially improves its members' cigarette tax structure. The specific tax overcomes the weakness of the ad valorem excise tax, since it does not depend on import or ex-factory values, which comprise only a small part of the retail price in ECOWAS countries. We recommend that WAEMU countries adopt the ECOWAS Directive, rather than the WAEMU Directive.


Growth and differentiation of intestinal endodermal cells in a coculture system.
To investigate the role of epithelial-mesenchymal interactions on intestinal maturation, we cultured embryonic epithelial cells in several experimental conditions. Microexplants of 14-15 days fetal rat intestinal endoderm, separated from the mesenchyme by collagenase, were seeded on dishes coated with different extracellular matrix components (collagens I, III, IV, fibronectin, laminin) or on confluent monolayers of intestinal mesenchymal cells or of fetal skin fibroblasts. Only small variations in the attachment or spreading of the endodermal cells could be observed when they were cultured on the different substrata and their survival never exceeded one week. When cocultured with intestinal or skin fibroblasts, however, endodermal cells grew, formed a monolayer, survival time was prolonged up to two to three weeks, and differentiation occurred. This differentiation was assessed by cell polarisation, morphological maturation of apical brush borders, synthesis of microvillar digestive enzymes and of extracellular matrix molecules seen immunocytochemically. Finally, glucocorticoids which are known to stimulate or induce brush border enzymes, accelerated the morphological and enzymatic maturation only in the cocultures.


Plasminogen Activator System and Breast Cancer: Potential Role in Therapy Decision Making and Precision Medicine.
Shifting from the historical TNM paradigm to the determination of molecular and genetic subtypes of tumors has been a major improvement to better picture cancerous diseases. The sharper the picture is, the better will be the possibility to develop subsequent strategies, thus achieving higher efficacy and prolonged survival eventually. Recent studies suggest that urokinase-type plasminogen activator (uPA), uPA Receptor (uPAR), and plasmino-gen activator inhibitor-1 (PAI-1) may play a critical role in cancer invasion and metastasis. Consistent with their role in cancer dissemination, high levels of uPA, PAI-1, and uPAR in multiple cancer types correlate with dismal prognosis. In this respect, upfront determination of uPA and PAI-1 as invasion markers has further opened up the possibilities for individualized therapy of breast cancer. Indeed, uPA and PAI-1 could help to classify patients on their risk for metastatic spreading and subsequent relapse, thus helping clinicians in their decision-making process to propose, or not propose, adjuvant therapy. This review covers the implications for cancer diagnosis, prognosis, and therapy of uPA and PAI-1, and therefore how they could be major actors in the development of a precision medicine in breast cancer.


Contrasting nitrogen and phosphorus budgets in urban watersheds and implications for managing urban water pollution.
Managing excess nutrients remains a major obstacle to improving ecosystem service benefits of urban waters. To inform more ecologically based landscape nutrient management, we compared watershed inputs, outputs, and retention for nitrogen (N) and phosphorus (P) in seven subwatersheds of the Mississippi River in St. Paul, Minnesota. Lawn fertilizer and pet waste dominated N and P inputs, respectively, underscoring the importance of household actions in influencing urban watershed nutrient budgets. Watersheds retained only 22% of net P inputs versus 80% of net N inputs (watershed area-weighted averages, where net inputs equal inputs minus biomass removal) despite relatively low P inputs. In contrast to many nonurban watersheds that exhibit high P retention, these urban watersheds have high street density that enhanced transport of P-rich materials from landscapes to stormwater. High P exports in storm drainage networks and yard waste resulted in net P losses in some watersheds. Comparisons of the N/P stoichiometry of net inputs versus storm drain exports implicated denitrification or leaching to groundwater as a likely fate for retained N. Thus, these urban watersheds exported high quantities of N and P, but via contrasting pathways: P was exported primarily via stormwater runoff, contributing to surface water degradation, whereas N losses additionally contribute to groundwater pollution. Consequently, N management and P management require different strategies, with N management focusing on reducing watershed inputs and P management also focusing on reducing P movement from vegetated landscapes to streets and storm drains.


Pseudothrombocytopenia due to platelet aggregation and degranulation in blood collected in EDTA.
Three patients are described in whom platelet aggregation and/or degranulation occurred in blood collected into EDTA. These changes resulted in spurious thrombocytopenia and morphological changes similar to those observed in some thrombocytopathies. The abnormalities were dependent on the presence of EDTA and did not occur in citrate, oxalate or heparin anticoagulants. In two patients the abnormality was shown to be due to a plasma factor which was not IgG, IgM, fibrinogen or albumin. The most likely explanation is that these patients have an unidentified abnormal plasma component which, on exposure to EDTA, develops 'anti-platelet activity'. Althought relatively uncommon a prospective study of the incidence of these phenomena indicates that they are probably more common than either platelet cold agglutinins or platelet satellitism. They have practical significance with respect to the diagnosis of thrombocytopenia and also to the interpretation of abnormal platelet morphology.


Tobacco myths: the older adult perspective.
Twenty adults ages 50 and older who had ceased using tobacco for 1 year or longer were interviewed. Participants provided personal insights into three myths found in the literature surrounding tobacco use and cessation in older adults and were asked to describe any perceived benefits of tobacco use. The findings indicate older adult tobacco users may need additional education on tobacco risks and cessation benefits provided by health care providers during routine office visits.


Examining the relationship between childhood animal cruelty motives and recurrent adult violent crimes toward humans.
Few researchers have studied the predictive ability of childhood animal cruelty motives as they are associated with later recurrent violence toward humans. Based on a sample of 180 inmates at one medium- and one maximum-security prison in a Southern state, the present study examines the relationship among several retrospectively identified motives (fun, out of anger, hate for the animal, and imitation) for childhood animal cruelty and the later commission of violent crimes (murder, rape, assault, and robbery) against humans. Almost two thirds of the inmates reported engaging in childhood animal cruelty for fun, whereas almost one fourth reported being motivated either out of anger or imitation. Only one fifth of the respondents reported they had committed acts of animal cruelty because they hated the animal. Regression analyses revealed that recurrent animal cruelty was the only statistically significant variable in the model. Respondents who had committed recurrent childhood animal cruelty were more likely to have had committed recurrent adult violence toward humans. None of the motives for committing childhood animal cruelty had any effect on later violence against humans.


Genetic interaction of GSH metabolic pathway genes in cystic fibrosis.
Cystic fibrosis (CF) is a monogenic disease caused by CFTR gene mutations, with clinical expression similar to complex disease, influenced by genetic and environmental factors. Among the possible modifier genes, those associated to metabolic pathways of glutathione (GSH) have been considered as potential modulators of CF clinical severity. In this way it is of pivotal importance investigate gene polymorphisms at Glutamate-Cysteine Ligase, Catalytic Subunit (GCLC), Glutathione S-transferase Mu 1 (GSTM1), Glutathione S-transferase Theta 1 (GSTT1), and Glutathione S-transferase P1 (GSTP1), which have been associated to the GSH metabolic pathway and CF clinical severity. A total of 180 CF's patients were included in this study, which investigated polymorphisms in GCLC and GST genes (GCLC -129C>T and -3506A>G; GSTM1 and GSTT1 genes deletion, and GSTP1*+313A>G) by PCR and PCR-RFLP associating to clinical variables of CF severity, including variables of sex, clinical scores [Shwachman-Kulczycki, Kanga e Bhalla (BS)], body mass index, patient age, age for diagnosis, first clinical symptoms, first colonization by Pseudomonas aeruginosa, sputum's microorganisms, hemoglobin oxygen saturation in the blood, spirometry and comorbidities. The CFTR genotype was investigated in all patients, and the genetic interaction was performed using MDR2.0 and MDRPT0.4.7 software. The analysis of multiple genes in metabolic pathways in diseases with variable clinical expression, as CF disease, enables understanding of phenotypic diversity. Our data show evidence of interaction between the GSTM1 and GSTT1 genes deletion, and GSTP1*+313A>G polymorphism with CFTR gene mutation classes, and BS (Balance testing accuracy=0.6824, p=0.008), which measures the commitment of bronchopulmonary segments by tomography. Polymorphisms in genes associated with metabolism of GSH act on the CF's severity.


Essential Ca(V)beta modulatory properties are AID-independent.
Voltage-gated Ca(2+) channel beta (Ca(v)beta) subunits have a highly conserved core consisting of interacting Src homology 3 and guanylate kinase domains, and are postulated to exert their effects through AID, the major interaction site in the pore-forming alpha(1) subunit. This stereotypical interaction does not explain how individual Ca(v)beta subunits modulate alpha(1) subunits differentially. Here we show that AID is neither necessary nor sufficient for critical Ca(v)beta regulatory properties. Complete modulation depends on additional contacts that are exclusive of AID and not revealed in recent crystal structures. These data offer a new context for understanding Ca(v)beta modulation, suggesting that the AID interaction orients the Ca(v)beta core so as to permit additional isoform-specific Ca(v)alpha(1)-Ca(v)beta interactions that underlie the particular regulation seen with each Ca(v)alpha(1)-Ca(v)beta pair, rather than as the main site of regulation.


[Changes in crisis intervention and emergency psychiatry, Amsterdam emergency consultations in 1983 and 2005].
Since 1992 The Netherlands has seen a striking increase in the number of compulsory admissions. There is a danger that coercion will become the dominant form of treatment in the Amsterdam clinics. To build up a picture of the changes in emergency psychiatry which have contributed to the increase in the number of acute compulsory admissions. A cohort (n = 460) of consultations conducted by the city crisis service in 1983 was compared with a similar cohort (n = 436) of consultations conducted in 2004-2005 based on the following variables: crisis-service procedures, patient characteristics, diagnosis and consultation outcomes. In 2003-2004 more services were involved with psychiatric patients in acute situations in the public domain than were involved in 1983. The number of patients referred by the police almost doubled, rising from 29.3 to 62.7%. In 1983 all consultations took place where the patients were located; in 2004-2005 60% took place at the premises of the crisis service. The number of psychotic patients in the cohort rose from 52 to 63.3%. There was a rise in the number of compulsory admissions (from 16.7 to 20%) and a sharp decline in voluntary admissions (from 25.7 to 7.6%). The total number of admissions following a consultation decreased from 42 to 28%. The front-line outreach service of 1983 has been transformed into a specialist psychiatric emergency department with only a modest outreach component. Voluntary admissions via the consultation service have almost ceased. Further research is needed into the characteristics of the consultations and into the variables that play a role in the use of compulsion in emergency psychiatry.


Ambulatory heart rate changes in patients with panic attacks.
Of 33 "panic" attacks reported by patients wearing an ambulatory solid-state heart rate/activity monitor for 6 days, 19 (58%) occurred at heart rates disproportionate to activity levels and different enough from surrounding heart rates to indicate a distinct physiologic state. Intense panic attacks with three or more symptoms were the most readily identified. ECG monitoring found the elevated heart rates to be sinus tachycardias. Heart rate elevation did not occur during anticipatory anxiety episodes. Ambulatory heart rate recordings confirm the presence of major physiologic changes during self-reported panic attacks.


Giant aneurysm of left anterior descending coronary artery treated by surgical off-pump therapy.
Coronary artery aneurysms may predispose to acute thrombosis, embolisation and myocardial ischaemia or rupture with subsequent tamponade and/or sudden death. The optimal therapy for patients with coronary artery aneurysm is unknown, and controversy persists regarding the use of medical or surgical modalities. There is no doubt that surgical therapy is reserved for cases with large aneurysms or with myocardial ischaemia due to significant associated coronary artery stenoses. We discuss here the surgical management of a case with coronary artery aneurysm and concomitant coronary artery disease. Although the beating heart technique of myocardial revascularisation and repair of coronary artery aneurysm without cardiopulmonary bypass is not suitable for all patients, it should be considered for those high-risk patients who have impaired left ventricular function or who are at high risk for pulmonary or neurological complications.


"Namaste Flap": Modification of Subcutaneous Pedicle Propeller Flaps in the Reconstruction of Postburn Axillary and Elbow Contractures.
The reconstruction of the postburn contracture area is always a challenge in the field of plastic surgery. Moreover, the joints are very sensitive to trauma and immobilization, showing a susceptibility to stiffness. The aim of this article is to emphasize the use of "Namaste flap"-modification of subcutaneous pedicle propeller flaps in the reconstruction of postburn axillary and elbow contractures. This is a prospective case study of axillary and elbow contractures managed at a tertiary care hospital using Namaste flap-modification of subcutaneous pedicle propeller flaps from 2010 to 2016. The surgical technique involved raising 2-limbed subcutaneous pedicle-based propellar flap over the contracture using the unburnt skin at the axillary and cubital fossa. The flap with both the limb thus raised was rotated by 90 degrees in the same direction and inserted into the defect. Nine patients including 6 patients with elbow and 3 patients with axillary contractures were included in this study. The mean degree of contracture in axilla and elbow was 78.3 degrees and 59.1 degrees, respectively. The functional results postoperatively were satisfactory. The mean postoperative degree of joint movements in axilla and elbow was 176.3 degrees and 173.6 degrees, respectively. No major complications were encountered. There was a mean period of 12 months of follow-up. In cases where normal skin is still present on the axillary and cubital fossa with scar contracture caused by extensive burns, the subcutaneous propeller flap methods and their modifications should be considered one of the most useful versatile reconstruction methods. Namaste flap in addition to the advantages of subcutaneous pedicle propeller flap also negates the disadvantages caused by the use of split skin grafting of the donor area.


Localization of sodium channels in cultured neural cells.
Sodium channels in cultured neural cells were localized by light microscopic autoradiography of specifically bound 125I-scorpion toxin. Ninety percent of the cell-bound 125I-scorpion toxin was associated specifically with sodium channels as assessed by the blocking of autoradiographic labeling by unlabeled scorpion toxin and by depolarization. Sodium channels were distributed uniformly in the surface membrane of neurites and cell bodies of both morphologically differentiated and undifferentiated cells of clone N18 of mouse neuroblastoma C1300. Sodium channels were distributed nonuniformly in many cultured spinal cord neurons. Visual observation indicated that 37 +/- 5% of cultured spinal cord neurons had a higher sodium channel density on the initial segment of one or more neurites than on the cell body. For these neurons, the density on one neurite initial segment averaged 7.4 +/- 1.9-fold greater than on the adjacent cell body. This increased sodium channel density may be the basis of the lower threshold for action potential generation at the axon initial segment of motor neurons and some spinal interneurons in vivo.


The future of employer-sponsored retiree medical plans.
Complex issues cloud the economic security of people who are covered by employer-sponsored retiree medical plans. The future stability of these plans is especially confusing. In their paper, the authors carefully analyze the current structure of retiree medical plans, including the effect of certain laws. Their clarifications are objective and concise. Of particular timeliness and practicality--particularly for public policy markers--is the authors' four-point strategy to help stabilize the future.


Usage frequencies of complement-taking verbs in Spanish and English: data from Spanish monolinguals and Spanish-English bilinguals.
Verb bias, or the tendency of a verb to appear with a certain type of complement, has been employed in psycholinguistic literature as a tool to test competing models of sentence processing. To date, the vast majority of sentence processing research involving verb bias has been conducted almost exclusively with monolingual speakers, and predominantly with monolingual English speakers, despite the fact that most of the world's population is bilingual. To test the generality of competing theories of sentence comprehension, it is important to conduct cross-linguistic studies of sentence processing and to add bilingual data to theories of sentence comprehension. Given this, it is critical for the field to develop verb bias estimates from monolingual speakers of languages other than English and from bilingual populations. We begin to address these issues in two norming studies. Study 1 provides verb bias norming data for 135 Spanish verbs. A second aim of Study 1 was to determine whether verb bias estimates remain stable over time. In Study 2, we asked whether Spanish-English speakers are able to learn verb-specific information, such as verb bias, in their second language. The answer to this question is critical to conducting studies that examine when, during the course of sentence comprehension, bilingual speakers exploit verb information specific to the second language. To facilitate cross-linguistic work, we compared our verb bias results with those provided by monolingual English speakers in a previous norming study conducted by Garnsey, Lotocky, Pearlmutter, and Myers (1997). Our Spanish data demonstrated that individual verbs showed significant similarities in their verb bias across the 3 years of data collection. We also show that bilinguals are able to learn the biases of verbs in their second language, even when immersed in the first language environment. Appendixes A-C, containing the bilingual norms discussed in the article, may be downloaded from http://brm.psychonomic-journals.org/content/supplemental.


NAC transcription factor ORE1 and senescence-induced BIFUNCTIONAL NUCLEASE1 (BFN1) constitute a regulatory cascade in Arabidopsis.
Senescence is a highly regulated process that involves the action of a large number of transcription factors. The NAC transcription factor ORE1 (ANAC092) has recently been shown to play a critical role in positively controlling senescence in Arabidopsis thaliana; however, no direct target gene through which it exerts its molecular function has been identified previously. Here, we report that BIFUNCTIONAL NUCLEASE1 (BFN1), a well-known senescence-enhanced gene, is directly regulated by ORE1. We detected elevated expression of BFN1 already 2 h after induction of ORE1 in estradiol-inducible ORE1 overexpression lines and 6 h after transfection of Arabidopsis mesophyll cell protoplasts with a 35S:ORE1 construct. ORE1 and BFN1 expression patterns largely overlap, as shown by promoter-reporter gene (GUS) fusions, while BFN1 expression in senescent leaves and the abscission zones of maturing flower organs was virtually absent in ore1 mutant background. In vitro binding site assays revealed a bipartite ORE1 binding site, similar to that of ORS1, a paralog of ORE1. A bipartite ORE1 binding site was identified in the BFN1 promoter; mutating the cis-element within the context of the full-length BFN1 promoter drastically reduced ORE1-mediated transactivation capacity in transiently transfected Arabidopsis mesophyll cell protoplasts. Furthermore, chromatin immunoprecipitation (ChIP) demonstrates in vivo binding of ORE1 to the BFN1 promoter. We also demonstrate binding of ORE1 in vivo to the promoters of two other senescence-associated genes, namely SAG29/SWEET15 and SINA1, supporting the central role of ORE1 during senescence.


Costing of a cardiac catheterisation procedure.
An attempt has been made to identify the main factors involved in the costing of a Cardiac Catheterisation Procedure (CCP). The technique of historical costing was used. The cost of a CCP worked out to Rs. 4265.21. The direct costs contributed 62%, the indirect costs 2.6% and expenses contributed 35% to the total cost. All these factors were found to be sensitive to the volume and duration of CCP, hence administrators must assist the staff of cardiac catheterisation laboratory (CCL) in controlling these two factors for the cost-effectiveness and efficient utilisation of the CCL.


Attitudes of Jordanian Oncology Nurses Toward Computerization.
The implementation of electronic health records is viewed as an effective method to increase safety, efficiency, and effectiveness of nursing care. Nurses are crucial to the successful adoption of electronic health records. The purpose of this study is to assess oncology nurses' attitude toward electronic health records in Jordan. A quantitative cross-sectional survey design was used, in which 271 nurses completed the Nurses' Attitudes Towards Computerization questionnaire. The majority of participants were female (62.4%), with average age of 27.6 (SD = 5.2) years. The mean attitude score was 63.4 (SD = 13.3). Nurses' managers and nurses who received training on the adopted electronic healthcare systems were found to have a more positive attitude toward computer use in clinical practice than other nurses. The findings of this study demonstrated that oncology nurses had a positive attitude toward computerization. Training programs and facilities within an institution should be available to improve nurses' attitudes and enable them to adopt electronic healthcare systems.


Antifungal Constituents of Piper crocatum and Their Activities as Ergosterol Biosynthesis Inhibitors Discovered via In Silico Study Using ADMET and Drug-Likeness Analysis.
Along with the increasing resistance of Candida spp. to some antibiotics, it is necessary to find new antifungal drugs, one of which is from the medicinal plant Red Betel (Piper crocatum). The purpose of this research is to isolate antifungal constituents from P. crocatum and evaluate their activities as ergosterol biosynthesis inhibitors via an in silico study of ADMET and drug-likeness analysis. Two new active compounds 1 and 2 and a known compound 3 were isolated, and their structures were determined using spectroscopic methods, while their bioactivities were evaluated via in vitro and in silico studies, respectively. Antifungal compound 3 was the most active compared to 1 and 2 with zone inhibition values of 14.5, 11.9, and 13.0 mm, respectively, at a concentration of 10% w/v, together with MIC/MFC at 0.31/1.2% w/v. Further in silico study demonstrated that compound 3 had a stronger ΔG than the positive control and compounds 1 and 2 with -11.14, -12.78, -12.00, and -6.89 Kcal/mol against ERG1, ERG2, ERG11, and ERG24, respectively, and also that 3 had the best Ki with 6.8 × 10-3, 4 × 10-4, 1.6 × 10-3, and 8.88 μM. On the other hand, an ADMET analysis of 1-3 met five parameters, while 1 had one violation of Ro5. Based on the research data, the promising antifungal constituents of P. crocatum allow P. crocatum to be proposed as a new antifungal candidate to treat and cure infections due to C. albicans.


The ultrasonographic features of nonimmune hydrops fetalis: a study of 30 successive patients.
Nonimmune hydrops fetalis (NHF) is four times as common as the immune form due to the efficacy of anti-D gamma globulin therapy and the lower incidence of Rh incompatibility. Forty successive patients were studied over a 10-year period. The diagnosis of NHF was made prenatally by ultrasonography in all 30 patients who had this examination. Ten patients did not have ultrasonography. NHF usually has a recognizable cause. Of those occurrences diagnosed at less than 21 weeks' gestation, the ultrasonographic features of fetal Turner syndrome--which include NHF--were present in 88.9%. All were fatal. In those diagnosed at over 21 weeks' gestation, the commonest associated disorder was fetal cardiac decompensation (48.3%). Fetal cardiac dysrhythmia was readily identified by real-time ultrasonography. In two patients with fetal supraventricular tachycardia and NHF at 32 weeks' gestation, cardioversion with prenatal digoxin therapy was attempted but was unsuccessful. Fetus-to-fetus transfusion resulted in NHF in only one fetus in each of five multiple pregnancies. NHF was fatal in 80% of newborns. Airway problems and pulmonary hypoplasia were the main causes of death in the neonate. Survivors came from those with tachydysrhythmia, congenital infection, Noonan syndrome, and the idiopathic form of NHF. When NHF is detected ultrasonographically, I recommend fetal cardiac ultrasonography; 2-D, M-mode, and Doppler imaging may also be needed. Fetal supraventricular tachycardia is a remediable condition and treatment in utero should be considered.


Hibernation.
Hibernation (multiday torpor) and daily torpor in heterothermic mammals and birds are characterized by pronounced temporal reductions in body temperature, energy expenditure, water loss, and other physiological functions and are the most effective means for energy conservation available to endotherms. Hibernators express multiday torpor predominately throughout winter, which substantially enhances winter survival. In contrast, daily heterotherms use daily torpor lasting for several hours during the rest phase. Although torpor is still widely considered to be a specific adaptation of cold-climate species, as we will see in this primer, it is used by many diverse species from all climate zones, including the tropics. While energy conservation during adverse conditions is an important function of torpor, it is also employed to permit energy-demanding processes such as reproduction and growth, especially when food supply is limited. Even migrating birds enter torpor to conserve energy for the next stage of migration. Although many heterothermic species will be challenged by anthropogenic influences such as habitat destruction, introduced species, novel pathogens and specifically global warming, not all are likely to be affected in the same way. In fact, as argued here, it is likely that opportunistic heterotherms may be better equipped to deal with these challenges than homeotherms because heterotherms have highly flexible energy requirements, can limit foraging and reduce the risk of predation, and often are also long-lived. In contrast, strongly seasonal hibernators, especially those restricted to mountain tops, and those that have to deal with new diseases that are difficult to combat at low body temperatures, are likely to be adversely affected.


[Induction of cell surface antigens on a lymphomatous cell line by gamma interferon].
The interferons are known to induce the expression of cell surface determinants. Gamma interferon, in particular, has been shown to enhance class II antigens (DR) on the cell surface. We used this gamma interferon to induce beta 2-microglobulin (beta 2 mu) and a minor, sex related transplantation antigen called H-Y on the surface of B lymphoma cells. The antitumor effect of interferon could thus be at least twofold: an antiviral effect already known and an increase of intercellular recognition (by cell surface marker enhancement); allowing the tumor cells to be "seen" better by cells of the immune system.


Quality of life in acne vulgaris: Relationship to clinical severity and demographic data.
Acne vulgaris is known to impair many aspects of quality of life. However, the correlation of this impairment with clinical severity remains equivocal despite various school, community and hospital-based studies. A hospital-based study was undertaken to measure the impairment of quality of life of patients of acne vulgaris and correlate it with the severity of lesions. This was a cross-sectional, questionnaire-based study in a cohort of 100 patients of acne vulgaris attending the outpatient department of our referral hospital. A physician measured the severity of lesions using the global acne grading system, and patients assessed quality of life by completing a questionnaire (Cardiff acne disability index). A correlation of these two was done; some additional correlations were brought out through demographic data collected from the patients. There was no correlation between the severity of acne vulgaris and an impaired quality of life. Patients who consumed alcohol and/or smoked cigarettes were found to have an impaired quality of life. While the severity of acne progressively lessened in older patients, the impact on quality of life increased. The sample size was small and there was a lack of guaranteed reliability on the self-reported quality of life. The severity of acne vulgaris does not correlate with impairment in quality of life.


LDOC1 gene expression in two patients with head and neck squamous cell carcinomas and Parkinson's disease.
Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world. Risk factors for this cancer include tobacco and alcohol use, ultraviolet light exposure, and viral infection. Parkinson's disease is one of the most common neurodegenerative disorders, with a prevalence of 3% in persons over the age of 65 years. Apoptosis is a programmed cell death machinery pivotal for normal development, the establishment of highly organized neuronal circuitry, and the elimination of cancer cells. It has been suggested that increased expression of proapoptotic genes is associated with head tumors. One of these genes is the leucine zipper, down-regulated in cancer 1 (LDOC1) gene. We report two interesting cases of a 79-year-old man and a 98-year-old woman, both with Parkinson's disease and well-differentiated multiple HNSCC, in whom we evaluated the possible differential expression of LDOC1. We found that LDOC1 gene expression was increased in both patients compared with three male and three female controls. Conclusions. These findings suggest that apoptosis may play a pathogenetic role in HNSCC.


Bi-allelic Loss of Human APC2, Encoding Adenomatous Polyposis Coli Protein 2, Leads to Lissencephaly, Subcortical Heterotopia, and Global Developmental Delay.
Lissencephaly is a severe brain malformation in which failure of neuronal migration results in agyria or pachygyria and in which the brain surface appears unusually smooth. It is often associated with microcephaly, profound intellectual disability, epilepsy, and impaired motor abilities. Twenty-two genes are associated with lissencephaly, accounting for approximately 80% of disease. Here we report on 12 individuals with a unique form of lissencephaly; these individuals come from eight unrelated families and have bi-allelic mutations in APC2, encoding adenomatous polyposis coli protein 2. Brain imaging studies demonstrate extensive posterior predominant lissencephaly, similar to PAFAH1B1-associated lissencephaly, as well as co-occurrence of subcortical heterotopia posterior to the caudate nuclei, "ribbon-like" heterotopia in the posterior frontal region, and dysplastic in-folding of the mesial occipital cortex. The established role of APC2 in integrating the actin and microtubule cytoskeletons to mediate cellular morphological changes suggests shared function with other lissencephaly-encoded cytoskeletal proteins such as α-N-catenin (CTNNA2) and platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (PAFAH1B1, also known as LIS1). Our findings identify APC2 as a radiographically distinguishable recessive form of lissencephaly.


Conditioning of neonatal pigs using low-dose chemotherapy and murine fetal tissue before murine hybridoma transplantation.
Immunosuppression, myeloablation, and the use of immunologically immature tissue can overcome major histocompatibility complex barriers by inducing tolerance. With the goal of inducing tolerance to BALB/c-derived murine hybridoma cells producing the 4C6 monoclonal antibody (mAb), we transplanted BALB/c fetal tissue into neonatal pigs during a regimen of low-dose conditioning with busulfan and cyclophosphamide. After the tolerance induction phase, animals received intraperitoneal injections of 4C6 mAb hybridoma cells. Evidence of persistence of injected cells over time was sought by molecular analysis of peripheral blood for the presence of mouse genomic sequences and circulating 4C6 mAb. Persistence of donor polymerase chain reaction signal during the entire duration of the study, detectable mAb titer for 6 weeks, and a twofold increase of mAb concentration after a boost hybridoma infusion was observed in one animal receiving six consecutive administrations of the conditioning regimen. Our model has the distinctive advantage of allowing functional monitoring of engrafted cells for studying tolerance induction strategies. In addition, this model could be the basis for approaches aimed at producing mAbs in tolerized large animals.


Comparison of the effect of different intensity exercise on a bicycle ergometer on postprandial lipidemia in type II diabetic patients.
Postprandial lipid clearance failure and lipoprotein disorders, which are independent risk factors for cardiovascular diseases are well-recognized in type II diabetes. Reduction of fats through exercise has been proved, though the mechanism is not well-defined, and the effects of different intensity exercise on postprandial lipidemia in diabetes type II is unknown. This study aims to find these effects using a cycle ergometer. On three different days, 15 type II diabetics (10 women and 5 men, with a mean age 42.07 ± 6.05 years, weight 94.64 ± 4.37 kg, height 159.78 ± 9.09 cm, and body mass index29.83 ± 3.93 kg/m2), consumed a full fat breakfast (750-800 kcal, 85% fat), and 150 min later, blood samples were taken from them to measure their lipid profile. The 1st day was the control day, without any exercises. Seven days later, 90 min after enriched breakfast, they did 30 min of exercise on the cycle ergometer with intensity of 55-70% of maximum heart rate (HRmax), and 14 days later, 90 min after enriched breakfast, they did 30 min of exercise with intensity of 70-85% of HRmax. According to Friedman non-parametric test, high-density lipoprotein (HDL) cholesterol serum level significantly increased after 30 min of moderate intensity exercise (P > 0.05, from 39.4 ± 5.2 to 48.6 ± 9.3), while this increase was insignificant after a higher intensity exercise. Neither intensity levels had any significant effects on triglyceride or on low-density lipoprotein cholesterol. Results showed that moderate intensity exercise was more effective in increasing HDL cholesterol level in type II diabetics.


[Research in theory and practice].
By means of a survey of international articles, the authors propose to demonstrate some factors which bear an influence on the development of research and investigation in nursing, some problems which affect it, and some strategies for its development inside a clinical-teaching environment. DEVELOPMENT OR RESEARCH AND INVESTIGATION IN NURSING: In the United States, Canada, United Kingdom, other European countries, especially Spain, the authors observed the strong relationship which exists between the development of research and investigation in Nursing and its incorporation in universities. RESEARCH AND INVESTIGATION IN CLINICS: In the opinion of many authors, the main field for research and investigation lies in clinical practice. The authors analyze seven basic requirements: academic curiosity; education in research and investigation; investigative activity; climate conducive to research and investigation; funds for research and investigation; dissemination of the results of research and investigation activities; and making use of the discoveries. TEACH AND INVESTIGATE: The authors point out strategies which enable a teacher to teach from an investigative approach and to stimulate students towards investigation at various levels according to the circumstances involved.


Trace elements improve survival of DTIC-treated mice with overt liver metastases of Lewis lung carcinoma.
Trace elements have been previously shown to have specific antimetastatic effects in a mouse 3LLHH liver metastasis model. Here we have analyzed the effect on the survival of animals with liver metastases. Trace elements administered per os at 500-5000 mg/kg/day did not affect the survival of animals with liver metastases. However, when trace element treatment was combined with dacarbazine (DTIC) administration, the survival of animals was significantly improved (55%). This effect was specific for DTIC since trace elements did not influence the effect of 5-fluorouracil on survival in this liver metastasis model. These data and those found in the literature all suggest that trace elements can specifically modulate the antitumoral/antimetastatic effects of chemotherapeutic agents.


Early predictors of unfavourable outcome in subjects with moderate head injury in the emergency department.
Subjects with moderate head injury are a particular challenge for the emergency physician. They represent a heterogeneous population of subjects with large variability in injury severity, clinical course and outcome. We aimed to determine the early predictors of outcome of subjects with moderate head injury admitted to an Emergency Department (ED) of a general hospital linked via telemedicine to the Regional Neurosurgical Centre. We reviewed, prospectively, 12,675 subjects attending the ED of a General Hospital between 1999 and 2005 for head injury. A total of 309 cases (2.4%) with an admission Glasgow Coma Scale (GCS) 9-13 were identified as having moderate head injury. The main outcome measure was an unfavourable outcome at 6 months after injury. The predictive value of a model based on main entry variables was evaluated by logistic regression analysis. 64.7% of subjects had a computed tomographic scan that was positive for intracranial injury, 16.5% needed a neurosurgical intervention, 14.6% had an unfavourable outcome at 6 months (death, permanent vegetative state, permanent severe disability). Six variables (basal skull fracture, subarachnoid haemorrhage, coagulopathy, subdural haematoma, modified Marshall category and GCS) predicted an unfavourable outcome at 6 months. This combination of variables predicts the 6-month outcome with high sensitivity (95.6%) and specificity (86.0%). A group of selected variables proves highly accurate in the prediction of unfavourable outcome at 6 months, when applied to subjects admitted to an ED of a General Hospital with moderate head injury.


18q deletion in a cystic fibrosis infant, increased morbidity and challenge for correct treatment choices: a case report.
Cystic Fibrosis (CF) is the most frequent recessive disease of Caucasian patients. Association with other diseases or syndromes has previously been reported. Co-morbidity may be a challenge for clinicians, who have to face more severe problems. We have described a CF infant, F508del homozygote, diagnosed by neonatal screening, who also had a chromosome 18q terminal deletion [del (18)(q22-qter)]. Some clinical features of the 18q deletion: e.g., cardiopathy, gastro-oesophageal reflux and severe muscular hypotonia, worsened the CF clinical picture and his quality of life, with repeated pulmonary exacerbations and failure to thrive in the first six months of life. The treatment strategy was chosen following an accurate multi-disciplinary team study of overlapping chromosome syndrome and CF symptoms. The use of a gastrostomy device for enteral nutrition together with a new device (Ez-PAP) for chest physiotherapy led to normal growth, a notably reduced hospitalization rate and improved quality of life. This case shows how co-morbidities worsening the clinical course of a "complicated patient" can be faced thanks to unconventional therapies that represent a challenge for clinicians.


Country-wide genetic monitoring over 21 years reveals lag in genetic recovery despite spatial connectivity in an expanding carnivore (Eurasian otter, Lutra lutra) population.
Numerous terrestrial mammal species have experienced extensive population declines during past centuries, due largely to anthropogenic pressures. For some species, including the Eurasian otter (Lutra lutra), environmental and legal protection has more recently led to population growth and recolonization of parts of their historic ranges. While heralded as conservation success, only few such recoveries have been examined from a genetic perspective, i.e. whether genetic variability and connectivity have been restored. We here use large-scale and long-term genetic monitoring data from UK otters, whose population underwent a well-documented population decline between the 1950s and 1970s, to explore the dynamics of a population re-expansion over a 21-year period. We genotyped otters from across Wales and England at five time points between 1994 and 2014 using 15 microsatellite loci. We used this combination of long-term temporal and large-scale spatial sampling to evaluate 3 hypotheses relating to genetic recovery that (i) gene flow between subpopulations would increase over time, (ii) genetic diversity of previously isolated populations would increase and that (iii) genetic structuring would weaken over time. Although we found an increase in inter-regional gene flow and admixture levels among subpopulations, there was no significant temporal change in either heterozygosity or allelic richness. Genetic structuring among the main subpopulations hence remained strong and showed a clear historical continuity. These findings highlight an underappreciated aspect of population recovery of endangered species: that genetic recovery may often lag behind the processes of spatial and demographic recovery. In other words, the restoration of the physical connectivity of populations does not necessarily lead to genetic connectivity. Our findings emphasize the need for genetic data as an integral part of conservation monitoring, to enable the potential vulnerability of populations to be evaluated.


An outbreak of acute postoperative endophthalmitis after cataract surgery.
Endophthalmitis is one of the most serious complications of ophthalmic surgery, which includes postoperative cataract extraction. Outbreak of acute postoperative endophthalmitis after cataract surgery has been reported in Thailand and other countries. To describe an outbreak of acute postoperative endophthalmitis after cataract surgery that was referred to Chiang Mai University Hospital during March 2006. Observational case series were made from the records of inpatients and outpatients, who had been referred for treatment of acute postoperative endophthalmitis after cataract surgery at a district hospital in northern Thailand. The surgery was conducted on two consecutive days by volunteer ophthalmologists of a non-profit foundation from Bangkok. In this outbreak, the authors recorded 31 endophthalmitis cases, with 33 eyes (bilateral 2 cases). Of the 33 endophthalmitis eyes, 32 occurred following extracapsular cataract extraction with intraocular lens and one after the secondary intraocular lens implant. Microbiological investigations in the hospital were done with aqueous tapping, vitreous tapping, and vitreous from pars plana vitrectomy. Gram-positive cocci were detected from vitreous tapping in four eyes. Thirty-two cases were managed with intravitreous antibiotics, one with subconjunctival antibiotic only, and all eyes were treated with fortified topical antibiotics. Fifteen eyes underwent pars plana vitrectomy Assessment of visual acuity (VA) before and after treatment showed improvement in 75.8% (25/33), decrease of VA in 9.1% (3/33), while visual acuity remained stable in 15.2% (5/33). In high-volume cataract surgery, an outbreak of endophthalmitis is always possible. Prompt and appropriate treatment can improve the visual outcome.


Subject and Family Perspectives from the Central Thalamic Deep Brain Stimulation Trial for Traumatic Brain Injury: Part II.
This is the second paper in a two-part series describing subject and family perspectives from the CENTURY-S (CENtral Thalamic Deep Brain Stimulation for the Treatment of Traumatic Brain InjURY-Safety) first-in-human invasive neurological device trial to achieve cognitive restoration in moderate to severe traumatic brain injury (msTBI). To participate, subjects were independently assessed to formally establish decision-making capacity to provide voluntary informed consent. Here, we report on post-operative interviews conducted after a successful trial of thalamic stimulation. All five msTBI subjects met a pre-selected primary endpoint of at least a 10% improvement in completion time on Trail-Making-Test Part B, a marker of executive function. We describe narrative responses of subjects and family members, refracted against that success. Interviews following surgery and the stimulation trial revealed the challenge of adaptation to improvements in cognitive function and emotional regulation as well as altered (and restored) relationships and family dynamics. These improvements exposed barriers to social reintegration made relevant by recoveries once thought inconceivable. The study's success sparked concerns about post-trial access to implanted devices, financing of device maintenance, battery replacement, and on-going care. Most subjects and families identified the need for supportive counseling to adapt to the new trajectory of their lives.