Adverse reaction and rational use of paracetamol tablets and its drug content detection based on spectral test.
Paracetamol and amantadine hydrochloride tablet is a commonly used drug to relieve the common cold. Its main ingredient is 4-Acetamidophenol. The safety of acetaminophen containing cold drugs has attracted more and more attention in recent years. In order to promote the clinical safety of drugs, the adverse reaction and clinical application of acetaminophen drugs are analyzed in this paper. The adverse reactions induced by acetaminophen mainly include: allergic reaction (46.1%), liver and kidney injury (25%), blood system (15.7%) and digestive system (5.2%). At the same time, we tested the content of acetaminophen by using spectral test. It can be seen that the method can be extended to the quantitative analysis and quality control of the effective components of other compound drugs.


Advances in Point-of-Care Thoracic Ultrasound.
Pulmonary ultrasound continues to develop and is ideally suited for the evaluation and treatment of respiratory emergencies. It is portable, can be performed rapidly, has no ionizing radiation, and is highly sensitive and specific for the diagnosis of pneumothorax, pneumonia, pulmonary edema, and free fluid in the chest.


Food-grade argan oil supplementation in molasses enhances fermentative performance and antioxidant defenses of active dry wine yeast.
The tolerance of the yeast Saccharomyces cerevisiae to desiccation is important for the use of this microorganism in the wine industry, since active dry yeast (ADY) is routinely used as starter for must fermentations. Both biomass propagation and dehydration cause cellular oxidative stress, therefore negatively affecting yeast performance. Protective treatments against oxidative damage, such as natural antioxidants, may have important biotechnological implications. In this study we analysed the antioxidant capacity of pure chemical compounds (quercetin, ascorbic acid, caffeic acid, oleic acid, and glutathione) added to molasses during biomass propagation, and we determine several oxidative damage/response parameters (lipid peroxidation, protein carbonylation, protective metabolites and enzymatic activities) to assess their molecular effects. Supplementation with ascorbic, caffeic or oleic acids diminished the oxidative damage associated to ADY production. Based on these results, we tested supplementation of molasses with argan oil, a natural food-grade ingredient rich in these three antioxidants, and we showed that it improved both biomass yield and fermentative performance of ADY. Therefore, we propose the use of natural, food-grade antioxidant ingredients, such as argan oil, in industrial processes involving high cellular oxidative stress, such as the biotechnological production of the dry starter.


Epidermal enzymes: their role in homeostasis and their relationships with dermatoses.
This review underlines the importance of different enzymes (beta-glucocerebrosidase, phospholipase A2, proteases and cholesterol sulfatase) in the formation and maintenance of the epidermal barrier function. Certain diseases may be characterized by the lack or excess of one or more of these different enzyme activities, altering the homeostatic equilibrium of the epidermis. In addition to this, particular enzymes may show potential in the development of novel dermocosmetic strategies.


Photodynamic Therapy is an Effective Treatment of Facial Pigmented Actinic Keratosis.
Actinic keratosis (AK), or solar keratosis, is a precancerous condition of the skin, mainly caused by excessive and chronic exposure to ultraviolet radiation. Pigmented AK (pAK) is a rare variant of AK. Photodynamic therapy (PDT) is widely used to treat the classical variant of AK, but very limited data are available on the use of PDT in patients with pAK. The objective of this study was to assess the usefulness of PDT in the treatment of pAK. The study included 16 patients with 20 pAK lesions treated with PDT. All skin lesions were clinically and dermatoscopically assessed for typical features characteristic of pAK. Reflectance confocal microscopy (RCM) was also used to assess keratinocyte atypia, confirm pAK diagnosis, and rule out other disease entities. After three PDT sessions, the complete resolution of all clinical features of pAK was observed in 80% of the studied lesions. Dermatoscopically, 65% of the lesions achieved 100% response and no cellular atypia was seen in the follow-up RCM images of 85% of lesions. Photodynamic therapy is an effective treatment modality for pAK in fair-skinned individuals.


Validation of the indirect TaSP enzyme-linked immunosorbent assay for diagnosis of Theileria annulata infection in cattle.
An ELISA based on a recombinant Theileria annulata surface protein (TaSP) was evaluated for detection of antibodies in sera from cattle exposed to tropical theileriosis in Sudan. The reference positive samples, used in this study, were from Theileria-infected populations and consisted of 80 cattle from an endemic area in Khartoum State, with high antibody titers in the indirect fluorescent antibody test (IFAT). The reference negative samples were taken from non-exposed populations and consisted of 120 cattle maintained under strict tick control at a commercial farm in Sudan. The cut-off value determined by Two-Graph Receiver-Operating Characteristic (TG-ROC) curves was set at 31.6%, based on the positive reference samples. Further diagnostic validation was performed, which consisted of the measurement of the area under the ROC (AUC) and by valid range proportion (VRP), which was 0.97 and 0.98 for the cut-off, respectively. There were no cross-reactions with antibodies raised against Babesia spp. It is concluded that the TaSP ELISA is a useful test for the diagnosis of T. annulata infection in cattle under field conditions.


A sexual arousability model involving steroid effects at the plasma membrane.
This review will discuss the status of research related to sexual arousability. It will also present a model for sexual arousability based on current knowledge of steroids effects at the membranes of cells. Steroids have multiple rapid actions that are suggested to result from actions at membrane-associated receptors. When stimulated by steroids these receptors alter G-protein coupling in a manner unique to this complex. Initial stimulation of the receptors by steroids alters the coupling pattern of G-proteins and of other binding sites associated with the complex. This change in G-protein coupling is a stable alteration and thus may serve as a long-term change in the system, which is a requirement of sexual arousability. Stimulation of this receptor system by a surge of oxytocin at ejaculation or orgasm then decouples the G-protein and reduces arousability. Sex hormone binding globulin may be an important ligand at this complex. This model suggests completely new relationships among steroids and their receptors that may complement or diverge from actions at known intracellular receptors.


Structure, regulation, and host interaction of outer membrane protein U (OmpU) of Vibrio species.
OmpU is a multimeric, cation selective outer membrane protein of Vibrio and related species that non-covalently interact with peptidoglycan layer. Interaction of OmpU with human host cells triggers signaling pathways to promote cytokine secretion, reactive oxygen species production, and caspase independent death in immune and epithelial cells. Non-choleric OmpU imparts resistance to antimicrobial peptides and induces actin cytoskeletal reorganization in the host cells. Further, OmpU isolated from Vibrio species elicits an immune response in several aquaculture hosts. Importantly, in-vivo studies using recombinant OmpU or OmpU derived mimotopes reveal a short-lasting immunity, and protection against Vibrio in the aquaculture sector. In conclusion, OmpU is a key adhesion protein and an important virulence factor for successful colonization of Vibrio species into hosts. This review article provides a broad overview of structural, regulatory, and functional mechanisms of OmpU in normal and disease states.


Sphingosine 1-phosphate dynamically regulates myosin light chain phosphatase activity in human endothelial cells.
Sphingosine 1-phosphate (S1P) is known to induce reorganization of the actin cytoskeleton through activation of the GTPase Rho. We have investigated the dynamic behavior of Rho/Rho kinase-regulated myosin light chain (MLC) phosphatase activity and MLC phosphorylation in Human Umbilical Vein Endothelial Cells (HUVEC) stimulated with S1P. Immediately (30-60 s) after S1P stimulation, MLC phosphatase activity dropped and MLC phosphorylation increased in a Rho/Rho kinase-dependent manner. Shortly thereafter (2 min), MLC phosphatase increased above baseline and MLC phosphorylation correspondingly decreased to near control values. At this time point, formation of actin ruffles and Rac activity assays indicated activation of Rac. Finally, between 5 and 15 min, MLC phosphatase dropped to a plateau below baseline. In parallel, MLC phosphorylation became constantly elevated above control values. These findings indicate that S1P is able to induce dynamic cycles of MLC phosphatase deactivation and activation. This novel feature of S1P could contribute to its chemotactic and angiogenic activity.


Normalization of serum C1q after intravenous immunoglobulin infusions in hypogammaglobulinemia: dependence upon methods of immunoglobulin preparation.
Low levels of serum complement subcomponent C1q may accompany primary humoral immunodeficiency diseases such as sex-linked agammaglobulinemia, severe combined immunodeficiency, and common varied immunodeficiency. This selective depression of C1q is proportional to the degree of hypogammaglobulinemia, and is corrected in severe combined immunodeficiency by bone marrow transplantation or in hypogammaglobulinemia by immunoglobulin infusions, possibly because C1q is stabilized by IgG by reversible interactions which reduce extravascular degradation. In this study it is shown that a pH 4.0 treated intravenous gamma-globulin (ivGG) and a reduced and alkylated ivGG can equally increase levels of serum IgG, but that only the pH 4.0 preparation can raise C1q levels into the normal range. These findings show that some of the methods used to produce immunoglobulins suitable for intravenous use may hinder the ability of these molecules to stabilize Clq. The clinical implications of this observation remain unclear.


Observations on community screening for alcohol problems: a pilot project to assess the feasibility of identifying heavy drinkers in a community setting.
Using a standard computerised alcohol screening questionnaire including the CAGE and SMAST instruments, 122 subjects in a suburban shopping centre in Perth, Western Australia, were screened in an attempt to estimate the prevalence of hazardous drinking and to investigate knowledge of and attitudes to safe and heavy alcohol consumption.


Modelling the laminar connectome of the human brain.
The human connectome is the complete structural description of the network of connections and elements that form the 'wiring diagram' of the brain. Due to the current scarcity of information regarding laminar end points of white matter tracts inside cortical grey matter, tractography remains focused on cortical partitioning into regions, while ignoring radial partitioning into laminar components. To overcome this biased representation of the cortex as a single homogenous unit, we use a recent data-derived model of cortical laminar connectivity, which has been further explored and corroborated in the macaque brain by comparison to published studies. The model integrates multimodal MRI imaging datasets of both white matter connectivity and grey matter laminar composition into a laminar-level connectome. In this study, we model the laminar connectome of healthy human brains (N = 30) and explore them via a set of complex network measures. Our analysis demonstrates a subdivision of network hubs that appear in the standard connectome into each individual component of the laminar connectome, giving a fresh look into the role of laminar components in cortical connectivity and offering new prospects in the fields of both structural and functional connectivity.


Early effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on rat thymocytes in vitro.
TCDD is known to induce thymic atrophy in several mammalian species through activation of programmed cell death, or apoptosis. To investigate the time course of events which precede TCDD-induced thymic apoptosis in vitro, experiments were performed with thymocytes isolated from immature rats. Peak accumulation of both total and specifically bound [3H]TCDD was observed at 60 min post incubation. Incubation of cells with 10 nM TCDD resulted in significant increases in RNA polymerase activity and incorporation of [3H]uridine at 30 min, indicating increased RNA synthesis in response to TCDD. TCDD-induced stimulation of [3H]uridine incorporation was not significantly altered in the presence of cycloheximide, while this effect was abrogated in the presence of actinomycin D. Incubation of thymocytes with 10 nM TCDD also stimulated the activity of poly(A)polymerase, the enzyme catalyzing mRNA polyadenylation, at time points beyond 30 min. No significant increases in [35S] incorporation were observed in cells treated with 10 nM TCDD, although analysis of detergent and high salt extracted nuclear proteins by SDS-PAGE and coomassie blue staining revealed the increased abundance of at least two proteins with molecular masses of 52,000 and 42,000 Da, respectively. These studies reveal that thymocyte nuclei rapidly accumulated TCDD in vitro, leading to increased RNA synthesis, poly(A)polymerase activity and protein synthesis. These events correlate closely with the process of programmed cell death.


A Proficiency-Based Progression Simulation Training Curriculum to Acquire the Skills Needed in Performing Arthroscopic Bankart and Rotator Cuff Repairs-Implementation and Impact.
To investigate the impact of a proficiency-based progression (PBP) curriculum employed to teach trainees in the skills needed to demonstrate proficiency for an arthroscopic Bankart repair (ABR) and an arthroscopic rotator cuff repair (ARCR) by objectively comparing pre- and immediate postcourse performances. In a prospective study, 16 arthroscopy/sports medicine fellows and 2 senior residents (complete group: N = 18) were randomly assigned to perform a precourse cadaveric ABR (Bankart subgroup: N = 6), ARCR (cuff subgroup: N = 6), or basic skills on a shoulder simulator (N = 6). After completing a PBP training curriculum, all 18 registrants performed both an ABR and ARCR scored in real time by trained raters using previously validated metrics. The Bankart subgroup made 58% fewer objectively assessed errors at the completion of the course than at baseline (P = .004, confidence interval -1.449 to -0.281), and performance variability was substantially reduced (standard deviation = 5.89 vs 2.81). The cuff subgroup also made 58% fewer errors (P = .001, confidence interval -1.376 to 0.382) and showed a similar reduction in performance variability (standard deviation = 5.42 vs 2.1). Only one subject's precourse baseline performance met the proficiency benchmark compared with 89% and 83% of the all registrants on the final ABR and ARCR cadaveric assessments, respectively. The results of this study reject the null hypothesis. They demonstrate that the implementation of a PBP simulation curriculum to train the skills necessary to perform arthroscopic Bankart and rotator cuff repairs results in a large and statistically significant improvement in the trainee's ability to meet the 2 related performance benchmarks. Proficiency was demonstrated by 89% and 83% of the trainees for an ABR and an ARCR, respectively, in a two- and one-half day course. Surgical training employing a PBP curriculum is efficient, effective, and has the potential to improve patient safety.


Correlates of physical and emotional health among Native American adolescents.
To examine the risk and protective factors among Native American youth that are correlated with both physical and emotional health. The study was based upon the National American Indian Adolescent Health Survey (n = 13,454), conducted using students self-categorized into a ranked variable of physical health ("poor," "fair," "good," or "excellent") and a continuous variable of emotional health based upon a nine-item unidimensional scale (overall Cronbach's alpha of .74). Twenty-nine variables derived from resilience theory encompassing both risk and protective factors were selected. Associations with physical and emotional health were examined using linear regression analysis. Identified protective factors explained approximately 30% of variance for emotional health, with family caring explaining nearly 15% of variance for both genders. The most significant associations for emotional health for females were family caring, body pride, feelings about school, and worries or concerns particularly about violence. For males, most significant protective factors included family caring, body pride, parental expectations, and type of sexual attraction. For physical health, the identified variables explained only 16% of variance for both genders. Body pride was the most significant association, explaining 10% of variance. Connection to family remains a consistently powerful factor in the lives of these youth. Other associations including body pride and parental expectations may help in the exploration and buffering of emotional health among American Indian youth.


A comprehensive set of ER protein disulfide isomerase family members supports the biogenesis of proinflammatory interleukin 12 family cytokines.
Cytokines of the interleukin 12 (IL-12) family are assembled combinatorially from shared α and β subunits. A common theme is that human IL-12 family α subunits remain incompletely structured in isolation until they pair with a designate β subunit. Accordingly, chaperones need to support and control specific assembly processes. It remains incompletely understood, which chaperones are involved in IL-12 family biogenesis. Here, we site-specifically introduce photocrosslinking amino acids into the IL-12 and IL-23 α subunits (IL-12α and IL-23α) for stabilization of transient chaperone-client complexes for mass spectrometry. Our analysis reveals that a large set of endoplasmic reticulum chaperones interacts with IL-12α and IL-23α. Among these chaperones, we focus on protein disulfide isomerase (PDI) family members and reveal IL-12 family subunits to be clients of several incompletely characterized PDIs. We find that different PDIs show selectivity for different cysteines in IL-12α and IL-23α. Despite this, PDI binding generally stabilizes unassembled IL-12α and IL-23α against degradation. In contrast, α:β assembly appears robust, and only multiple simultaneous PDI depletions reduce IL-12 secretion. Our comprehensive analysis of the IL-12/IL-23 chaperone machinery reveals a hitherto uncharacterized role for several PDIs in this process. This extends our understanding of how cells accomplish the task of specific protein assembly reactions for signaling processes. Furthermore, our findings show that cytokine secretion can be modulated by targeting specific endoplasmic reticulum chaperones.


Duration criterion of respiratory events for children with obstructive sleep apnea.
To investigate the duration criterion of respiratory events in children with obstructive sleep apnea syndrome (OSAS) by analyzing standard nocturnal polysomnograms (PSG). To provide reference values for pediatric PSG. 107 OSAS children diagnosed by PSG from January 2004 to May 2006 were randomly selected. The decrease in arterial oxygen saturation (ΔSaO2) and the corresponding event duration of each respiratory event were observed. (1) There was significant positive correlation between oxygen desaturation values (ΔSaO2=0-17%) and the corresponding durations of respiratory events (P<0.001). (2) There was no significant difference in durations of respiratory events in rapid eye movement (REM) sleep and NREM sleep, the demographics between male and female children. (3) Significant positive correlation between age and duration of respiratory events (apnea/hypopnea) when oxygen desaturation values equal to 4% (ΔSaO2=4%) was observed. (4) The lower limit of 95% confidence intervals of which duration of oxygen desaturation value equals to 4% was 5.4s. (1) PSG studies may allow the establishment of the duration criterion of significant respiratory events; (2) 5.4s can be defined as duration criteria of respiratory events; (3) the present study provides reference values for Pediatric PSG.


Bacterial lipopolysaccharide depresses spontaneous, evoked, and ionophore-induced transmitter release at the neuromuscular junction.
The neurotoxocity of RNA-free lipopolysaccharide (LPS) extracted from Salmonella Typhimurium (SR-11) was tested at the frog neuromuscular junction using intracellular recording techniques. Spontaneous miniature endplate potential (MEPP) frequency was reduced to 45% of control after 60 minutes in the presence of 10 and 50 micrograms LPS/ml Ringer's solution. Elevation of extracellular [Ca] to 10 mM converted the MEPP frequency response to a biphasic pattern of early acceleration followed by late depression. Evoked endplate potentials (EEPs) were reduced in quantal content until phasic release of transmitter was abolished, while MEPP amplitude and endplate resting potential remained constant. Effects of the potent cation ionophore X537A on MEPP frequency were blocked by 45 minutes of pre-exposure to LPS. Because of its extremely lipophilic character, LPS apparently alters the physical structure of the presynaptic terminal membrane, eventually reducing resting and phasic Ca influx, and isolating the presynaptic terminal from ionophore action.


Ligament and tendon oxygenation measurements using polarographic oxygen sensors.
This pilot study was designed to investigate a new flexible polarographic oxygen sensor for intraarticular oxygen tissue tension monitoring, as a first step in designing a combined simultaneous oxygen and perfusion monitor. The tendoachilles in the sheep provided the initial testing model, which was followed by in vivo testing in the human knee. In the animal model, the tendoachilles was perforated by a single needle through which the new flexible multichannel polarographic oxygen sensor probe was passed. Variations in blood and oxygen delivery to the hindlimb were then produced by tourniquet and fraction of inspired oxygen (FiO2) changes. The oxygen sensors appropriately recorded current variations proportional to the hypothesized oxygen delivery. In the human model, the anterior cruciate ligament (ACL) in five human knees was exposed during routine total knee replacement surgery and stripped of the fat pad and synovial attachments. The probe was inserted into the substance of the ligament from distal to proximal. Oxygen measurements were taken with the tourniquet elevated and then inflated, in an effort to evaluate the response of the oxygen sensors and to establish the degree of oxygenation that the bone blood supply provides to the ACL. In the sheep, 100% of the time (13 of 13 events), the current changed appropriately to a change in the FiO2. Ninety-four percent of the time (17 of 18 events), the current changed appropriately to a tourniquet change. In the human ACL, the probe was 83% sensitive (5 of 6 events) to a tourniquet change. The FiO2 changes were inconclusive owing to an insufficient amount of time allowed for tissue perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Prosepective Study to Evaluate Rate and Frequency of Perturbations of Implanted Programmable Hakim Codman Valve After 1.5-Tesla Magnetic Resonance Imaging.
Exposure to magnetic fields may alter the settings of programmable ventriculoperitoneal shunt valves or even cause permanent damages to these devices. There is little information about this topic, none on live patients. To investigate the effects of 1.5-tesla magnetic resonance imaging (MRI) on Hakim-Codman (HC) pressure programmable valves implanted in our hospital. A single-center prospective study to assess the rate of perturbations of HC programmable valve implanted. One hundred consecutive patients implanted for different clinical reasons between 2008 and 2012 were examined. A conventional skull x-ray before and after a standard MRI on 1.5 tesla. We evaluated before and after results, analyzed modification rate, and verified eventual damages to the implanted devices. Implanted HC valves are extremely handy and durable, even if they are likely to change often due to the exposure to magnetic fields. None of the patients complained of heating effects. Oscillations range from 10-30 mm H2O with a patient who reached 50 mm H2O and 1 who reached 60 mm H2O. Global alteration rate was 40%: 10 patients (10%) experienced a 10 mm H2O change; 14 patients (14%) had a 20 mm H2O change; 6 patients (6%) had a 30 mm H2O change; 8 patients (8%) had a 40 mm H2O change; 1 patient had a 50 mm H2O change; and 1 patient had a 60 mm H2O change. HC valves presented a variable perturbation rate, with an alteration rate of 40% with 1.5-telsa MRI. We have not observed malfunctioning hardware as a result of magnetic influence. We claim  a cranial x-ray immediately after the MRI because of a high risk (40%) of decalibration, especially in patients with low ventricles compliance.


Serum concentrations of vitamin D metabolites in different degrees of impaired renal function. Estimation of renal and extrarenal secretion rate of 24,25-dihydroxyvitamin D.
The serum levels of 25-hydroxycholecalciferol, 24,25-dihydroxycholecalciferol, and 1,25-dihydroxycholecalciferol were measured simultaneously in three groups of adults with different renal function: normal (n = 24), glomerular filtration rate (GFR) greater than 70 ml/min; moderately decreased (n = 15), GFR 5-35 ml/min, and severely decreased (n = 27), GFR less than 5 ml/min. 25-hydroxycholecalciferol was normal in both patient groups with decreased renal function. 1,25-dihydroxycholecalciferol was halved in the group with moderately decreased renal function (p less than 0.01) and severely decreased (almost undetectable) in the group with severely decreased renal function (p less than 0.01). In contrast, 24,25-dihydroxycholecalciferol was normal in the group with moderately decreased renal function and only halved (p less than 0.05) in the group with severely decreased renal function. These findings suggest extrarenal C-24 hydroxylase activity which may be stimulated by decreasing renal function, thus decreasing renal C-24 hydroxylase activity.


Polyphenol containing Sargassum horneri attenuated Th2 differentiation in splenocytes of ovalbumin-sensitised mice: involvement of the transcription factors GATA3/STAT5/NLRP3 in Th2 polarization.
Sargassum horneri (Turner) C. Agardh (Sargassaceae) is a brown marine alga used in oriental medicine to treat allergic conditions. This study clarifies the effect of polyphenol-containing S. horneri ethanol extract (SHE) on T-helper type-2 (Th2) polarisation. All mice (BALB/c mice, n = 12) except in the healthy control group were first sensitised with an intraperitoneal injection of ovalbumin (OVA; 20 µg) and alum (2 mg) on Day 0 and Day 14. Similarly, phosphate-buffered saline (PBS) was injected according to the same schedule into the healthy control mice. After the final administration, splenocytes were obtained. OVA sensitised mice were challenged with OVA (100 µg/mL) in the absence or presence (62.5 and 125 µg/mL) of SHE while healthy control group remained untreated. SHE (0-1000 µg/mL) was not cytotoxic to splenocytes and demonstrated IC50 values of 3.27 and 3.92 mg/mL, respectively, at 24 and 48 h of incubation. SHE suppressed cell proliferation at concentrations ≥62.5 µg/mL. SHE treatment (125 µg/mL) subdued (by 1.8-fold) the population expansion of CD3+CD4+ helper T cells induced by OVA challenge. SHE attenuated the OVA-induced activation of respective transcription factors GATA3 and NLRP3. Simultaneously, highly elevated levels of cytokines interleukin (IL)-4 and IL-5 caused by OVA stimulation were removed completely and IL-13 suppressed by 1.5-fold. SHE exhibits Th2 immune suppression under OVA stimulation via GATA3- and NLRP3-dependent IL-4, IL-5, and IL-13 suppression. Therefore, SHE could be therapeutically useful for alleviating the symptoms of allergen-mediated immune diseases.


The symptomatic, urodynamic and psychodynamic results of bladder re-education programs.
Bladder training and/or biofeedback techniques were used to treat 75 patients with frequency, urgency, nocturia and urge incontinence. Significant improvement or cure was obtained in 70 per cent of enuretic children, and 66 per cent of men and 74 per cent of women with unstable detrusor function. The clinical results correlated with cystometric reversion to stable bladder function. Patients who obtained good results showed improvement in the tested level of psychological adjustment, suggesting that psychological factors are not causes of the urological problem.


Modeling safe and unsafe driving behaviour.
A sample of 743 Dutch drivers was queried about driving-related errors and violations, and about the frequency of their accident involvement over the past 3 years. In addition, the following risky behaviours and characteristics related to driving were measured through self-report: strategic decisions made about driving before starting a trip, attitudes related to committing violations, psychological precursors of unsafe driving (such as being tired or stressed when driving), and physical precursors of unsafe driving (suffering physical or psychological handicaps when driving). The results show that several scales have acceptable reliability coefficients, though several others are in need of improvement. Path analysis showed that an acceptable structural model could be developed to describe all empirical relationships. Considerable parts of the variance in the violations scores and the psychological precursors scores could be explained by the other model variables. In terms of predictive power, "unsafe" attitudes, physical precursors, and psychological precursors had the most impact, each explaining up to 9% of the variance in violations scores, errors scores, and/or psychological precursors scores. The way these results can be utilized in future accident prevention programs and in driver training programs are indicated, as are their implications for future research.


Minimum standards of clinical practice for physiotherapists working in critical care settings in Australia and New Zealand: A modified Delphi technique.
Achieving competency in critical care in entry-level physiotherapy courses across Australia and New Zealand is not essential, and accredited training for qualified physiotherapists working in critical care units is lacking. As a result, practice standards and training may vary. The objective was to establish consensus-based minimum clinical practice standards for physiotherapists working in critical care settings in Australia and New Zealand. A modified Delphi technique, which consisted of three rounds of questionnaires, was used to obtain consensus on items. Australian and New Zealand critical care settings. A panel (n = 61) was invited from a pool of eligible physiotherapists throughout Australia and New Zealand (n = 93). Eligibility criteria were defined a-priori on the basis of possession of expertise and experience in the practice and teaching of critical care physiotherapy clinical skills. Questionnaires were disseminated electronically (either via email, or SurveyMonkey®). Items were designated by participants as being 'Essential/Unsure/Not Essential'. Consensus for inclusion was achieved when items were ranked 'Essential' by more than 70% of participants. Fifty physiotherapists consented and participated in the initial Delphi round, of whom 45 (90%) completed all rounds. Consensus was reached on 199 (89%) items. The panel agreed that 132 (58%) items were 'Essential' items for inclusion in the final framework. This is the first study to develop a consensus framework of minimum standards of practice for physiotherapists working in critical care. The clinical utility of this framework now requires assessment.


Tomato I2 Immune Receptor Can Be Engineered to Confer Partial Resistance to the Oomycete Phytophthora infestans in Addition to the Fungus Fusarium oxysporum.
Plants and animals rely on immune receptors, known as nucleotide-binding domain and leucine-rich repeat (NLR)-containing proteins, to defend against invading pathogens and activate immune responses. How NLR receptors respond to pathogens is inadequately understood. We previously reported single-residue mutations that expand the response of the potato immune receptor R3a to AVR3a(EM), a stealthy effector from the late blight oomycete pathogen Phytophthora infestans. I2, another NLR that mediates resistance to the will-causing fungus Fusarium oxysporum f. sp. lycopersici, is the tomato ortholog of R3a. We transferred previously identified R3a mutations to I2 to assess the degree to which the resulting I2 mutants have an altered response. We discovered that wild-type I2 protein responds weakly to AVR3a. One mutant in the N-terminal coiled-coil domain, I2(I141N), appeared sensitized and displayed markedly increased response to AVR3a. Remarkably, I2(I141N) conferred partial resistance to P. infestans. Further, I2(I141N) has an expanded response spectrum to F. oxysporum f. sp. lycopersici effectors compared with the wild-type I2 protein. Our results suggest that synthetic immune receptors can be engineered to confer resistance to phylogenetically divergent pathogens and indicate that knowledge gathered for one NLR could be exploited to improve NLR from other plant species.


Optimizing Radiotherapy with Immunotherapeutic Approaches.
Several factors must be considered to successfully integrate immunotherapy with radiation into clinical practice. One such factor is that concepts arising from preclinical work must be tested in combination with radiation in preclinical models to better understand how combination therapy will work in patients; examples include checkpoint inhibitors, tumor growth factor-beta (TGF-β) inhibitors, and natural killer (NK) cell therapy. Also, many radiation fields and fractionation schedules typically used in radiation therapy had been standardized before the introduction of advanced techniques for radiation planning and delivery that account for changes in tumor size, location, and motion during treatment, as well as uncertainties introduced by variations in patient setup between treatment fractions. As a result, radiation therapy may involve the use of large treatment volumes, often encompassing nodal regions that may not be irradiated with more conformal techniques. Traditional forms of radiation in particular pose challenges for combination trials with immunotherapy. This chapter explores these issues in more detail and provides insights as to how radiation therapy can be optimized to combine with immunotherapy.


Differential transcription of multiple copies of a silk worm gene encoding tRNA(Gly1).
Ten different tRNA(Gly1) genes from the silk worm, Bombyx mori, have been cloned and characterized. These genes were transcribed in vitro in homologous nuclear extracts from the posterior silk gland (PSG) or nuclear extracts derived from the middle silk gland or ovarian tissues. Although the transcription levels were much higher in the PSG nuclear extracts, the transcriptional efficiency of the individual genes followed a similar pattern in all the extracts. Based on the levels of in vitro transcription, the ten tRNA(Gly1) genes could be divided into three groups, viz., those which were transcribed at very high levels (e.g., clone pR8), high to medium levels (e.g., pBmi1, pBmp1, pBmh1, pBmt1) and low to barely detectable levels (e.g., pBms1, pBmj1 and pBmk1). The coding sequences of all these tRNA genes being identical, the differential transcription suggested that the flanking sequences modulate their transcriptional efficiency. The presence of positive and negative regulatory elements in the 5' flanking regions of these genes was confirmed by transcription competition experiments. A positive element was present in the immediate upstream A+T-rich sequences in all the genes, but no consensus sequences correlating to the transcriptional status could be generated. The presence of negative elements on the other hand was indicated only in some of the genes and therefore may have a role in the differential transcription of these tRNA(Gly1) genes in vivo.


Anti-inflammatory properties of mutolide isolated from the fungus Lepidosphaeria species (PM0651419).
Mutolide an anti-inflammatory compound was isolated from the coprophilous fungus Lepidosphaeria sp. (PM0651419). The compound mitigated LPS-induced secretion of pro-inflammatory cytokines TNF-α and IL-6 from THP-1 cells as well as human peripheral blood mononuclear cells (hPBMCs). Mutolide also inhibited secretion of another pro-inflammatory cytokine IL-17 from anti-hCD3/anti-hCD28 stimulated hPBMCs. NF-κB is the major transcription factor involved in the secretion of pro-inflammatory cytokines including IL-17. Mechanistic evaluations revealed that mutolide inhibited induced NF-κB activation and translocation from cytoplasm into the nucleus. However, mutolide did not significantly affect activity of p38 MAPK enzyme, a serine/threonine kinase involved in cell cycle proliferation and cytokine secretion. These results indicate that mutolide may exert its anti-inflammatory effect via NF-κB inhibition. Oral administration of mutolide at 100 mg/kg showed significant inhibition of LPS-induced release of TNF-α from Balb/c mice in an acute model of inflammation. Our results highlight the anti-inflammatory properties of mutolide and suggest that further evaluation in a chronic model of inflammation is required to confirm the potential of mutolide as a druggable candidate for the treatment of inflammatory diseases.


Fat cadherins in mouse models of degenerative ataxias.
Autophagy is a lysosomal degradation pathway that plays an essential role in neuronal homeostasis and is perturbed in many neurological diseases. Transcriptional downregulation of fat was previously observed in a Drosophila model of the polyglutamine disease Dentatorubral-pallidoluysian atrophy (DRPLA) and this was shown to be partially responsible for autophagy defects and neurodegeneration. However, it is still unclear whether a downregulation of mammalian Fat orthologues is associated with neurodegeneration in mice. We hereby show that all four Fat orthologues are transcriptionally downregulated in the cerebellum in a mouse model of DRPLA. To elucidate the possible roles of single Fat genes, this study concentrates on Fat3. This fat homologue is shown to be the most widely expressed in the brain. Conditional knockout (KO) of Fat3 in brains of adult mice was attempted using the inducible Thy1Cre(ERT2) SLICK H line. Behavioral and biochemical analysis revealed that mice with conditional KO of Fat3 in the brain display no abnormalities. This may be ascribed either to the limited efficiency of the KO strategy pursued or to the lack of effect of Fat3 KO on autophagy.


Transanal Minimally Invasive Surgery: State of the Art.
The treatment for rectal cancer and benign rectal lesions continues to progress in the arena of minimally invasive surgery. While surgical excision of the primary mass remains essential for eradication of disease, there has been a paradigm shift towards less invasive resection methods. Local excision is increasing in popularity for its low morbidity and excellent functional results in select patients. Transanal minimally invasive surgery (TAMIS) is a new technology developed to elevate the practice of local excision to state-of-the-art resection. The goal of this article is to evaluate the history, short-term outcomes, and evolution of the TAMIS technique for excision of benign and malignant rectal neoplasia.


Retention reproducibility of basic drugs in high-performance liquid chromatography on a silica column with a methanol-ammonium nitrate eluent. The effect of the mobile phase and the operating conditions.
The reproducibility of capacity factors and relative capacity factors are compared as methods for recording retentions for the high-performance liquid chromatography of basic drugs on a silica column with methanol-aqueous ammonium nitrate as the eluent. The effects of changing the column temperature and the ionic strength, pH and proportion of organic modifier in the eluent on the retentions and selectivity have been studied. The results suggest that the mobile phase and operating conditions must be closely defined in order to obtain results of adequate reproducibility to develop a data base of retention values for interlaboratory comparisons and/or for the identification of basic drugs.


Is low-intensity pulsed ultrasound effective for revitalizing a severely necrotic small bone? An experimental rabbit model.
Previously, we successfully applied a new method composed of drilling, bone marrow transplantation (BMT), external fixation and low-intensity pulsed ultrasound (LIPUS) for the clinical treatment of Kienböck's disease. The purpose of this study was to investigate whether bone regeneration can be induced by LIPUS and/or multiple drilling and/or BMT within a severely necrotic small-bone rabbit model. Eighteen rabbits were divided into three groups (BMT, drilling and control) and LIPUS stimulation was introduced daily for 8 weeks post-transplantation. Next, 12 additional rabbits were produced for the BMT group and LIPUS stimulation was introduced daily for 4 and 12 weeks (n = 6 for each). Histopathologically, new bone formations were rarely observed in the drilling and control groups. In the BMT group, the mineralizing surface areas of LIPUS(+) showed a significant increase compared with LIPUS(-) for 8 weeks. LIPUS treatment alone did not accelerate the revitalization of necrotic bones. However, LIPUS combined with BMT tended to promote new bone formation.


Ototoxicity (cochleotoxicity) classifications: A review.
Drug-mediated ototoxicity, specifically cochleotoxicity, is a concern for patients receiving medications for the treatment of serious illness. A number of classification schemes exist, most of which are based on pure-tone audiometry, in order to assist non-audiological/non-otological specialists in the identification and monitoring of iatrogenic hearing loss. This review identifies the primary classification systems used in cochleototoxicity monitoring. By bringing together classifications published in discipline-specific literature, the paper aims to increase awareness of their relative strengths and limitations in the assessment and monitoring of ototoxic hearing loss and to indicate how future classification systems may improve upon the status-quo. Literature review. PubMed identified 4878 articles containing the search term ototox*. A systematic search identified 13 key classification systems. Cochleotoxicity classification systems can be divided into those which focus on hearing change from a baseline audiogram and those that focus on the functional impact of the hearing loss. Common weaknesses of these grading scales included a lack of sensitivity to small adverse changes in hearing thresholds, a lack of high-frequency audiometry (>8 kHz), and lack of indication of which changes are likely to be clinically significant for communication and quality of life.


Effect of dietary fats on erythrocyte membrane lipid composition and membrane-bound enzyme activities.
Four different oil-based diets were used in a feeding study involving rats to assess the relationship between the fatty acid composition of the dietary fat and its influence on erythrocyte membrane (EM) lipid composition and the activities of membrane-bound enzymes. Nutritionally adequate diets containing 20% groundnut (GNO), coconut (CO), safflower (SO), or mustard oil (MO) were fed to weanling CFY rats for 4 months. EMs were analyzed for total cholesterol, phospholipids, fatty acid profiles, and sialic acid content. Activities of membrane-bound enzymes such as Na+, K(+)-adenosine triphosphatase (ATPase), Mg(2+)-ATPase, Ca2+, Mg(2+)-ATPase, and acetylcholinesterase were also assayed. The activities of all membrane-bound enzymes, except Mg(2+)-ATPase, and sialic acid content were higher in the MO-fed group than in the rest of the groups. Ca2+, Mg(2+)-ATPase activity was distinctly lower in the SO-fed group than in the other groups. Cholesterol to phospholipid molar ratio was similar in all the groups. However, SO- and MO-fed groups displayed an increased cholesterol content and a higher degree of unsaturation in the membrane fatty acid composition. The higher membrane fatty acid unsaturation in the SO-fed group was principally due to linoleic (18:2) and arachidonic (20:4) acids, while in the MO-fed group it was mainly due to oleic (18:1), eicosenoic (20:1), erucic (22:1), and linoleic (18:2) acids. These results suggest a relationship between the quality of dietary fat, EM fatty acyl composition, and the activities of membrane-bound enzymes.


Medications and diagnoses in relation to falls in a long-term care facility.
The association between falls, drugs, and diagnoses in elderly residents of a long-term care facility was explored using case-control methodology. The odds of being a faller rather than a control were significant (P less than .01) for those taking antidepressants, sedatives/hypnotics, or vasodilators, and for those with osteoarthritis or depression. When drug/diagnosis subgroups were examined, these same drug classes and diagnoses had high-odds ratios in the largest numbers of subgroups. In general, risk of falling appeared to be more strongly associated with drugs than with diagnoses.


Characterization of Rhopalosiphum padi takeout-like genes and their role in insecticide susceptibility.
Due to the extensive use of chemical insecticides, the field populations of Rhopalosiphum padi, a serious wheat pest worldwide, have developed resistance to insecticides. Therefore, deep understanding of the mechanisms of the aphid's physiological response to insecticides would be of importance for the management of insecticide resistance in pests. Takeout belongs to a protein superfamily found exclusively in insects. Previous research showed that the takeout gene had various functions in insect physiology and behavior. However, few studies have explored the functions of takeout in insect insecticide susceptibility. The susceptibility of R. padi to imidacloprid and beta-cypermethrin was tested. Thirteen takeout-like genes were identified based on the genome database of R. padi. The number of exons was variable in these takeout-like genes, and nine highly conserved amino acids (two Cysteine, two Proline, four Glycine and one Aspartic acid) were identified. Expression levels of takeout-like-2, takeout-like-3, takeout-like-5, takeout-like-8, takeout-like-10 and takeout-like-11 were significantly increased after imidacloprid treatment; seven genes (takeout-like-1, takeout-like-2, takeout-like-5, takeout-like-6, takeout-like-7, takeout-like-8 and takeout-like-11) tended to be upregulated after beta-cypermethrin treatment. RNA interference results showed that the mortalities of R. padi injected with dsTOL-2, dsTOL-5, dsTOL-8, dsTOL-10 and dsTOL-11 were significantly increased after exposure to imidacloprid in comparison with control (injection of dsGFP). Under two sublethal concentrations of beta-cypermethrin, the silencing of takeout-like-2, takeout-like-5 and takeout-like-11 significantly increased the mortalities of R. padi. These results provide evidence for the involvement of takeout-like genes in insecticide susceptibility of R. padi, which improves our understanding the determinant of insecticide susceptibility.


Interaction between estradiol and prolactin on vasoactive intestinal peptide concentrations in the hypothalamus and in the anterior pituitary of the female rat.
To determine whether vasoactive intestinal peptide (VIP) can be regulated by modification of plasma estradiol and prolactin levels, VIP concentrations in various structures of the rat brain and in the pituitary were measured in hyperprolactinemic female rats by means of a specific radioimmunoassay for the peptide. In ovariectomized rats treated with estradiol (E2) implants alone and with both E2 and pituitary grafts to induce an experimental hyperprolactinemia, VIP levels decreased in the anterior and mediobasal hypothalamus and increased in the pituitary as compared to ovariectomized rats. No modification of hypothalamic VIP concentrations was observed in ovariectomized rats with pituitary grafts only, whereas a significant increase was found in the pituitary. These results suggest that, in the female rats, E2 exerts an effect on hypothalamic VIP levels, probably through indirect mechanisms, and that this action can be enhanced by elevated plasma prolactin levels.


Hearing Screening in Children with Suspected Hearing Loss at a Tertiary Care Centre of Eastern Uttar Pradesh.
This study aims to comprehend the experience of hearing screening in children with suspected hearing loss at a tertiary care centre of eastern Uttar Pradesh, India using distortion product otoacoustic emission (DPOAE) as a screening modality. This study was conducted at a tertiary care centre of eastern Uttar Pradesh during the period of July, 2021to June, 2022 consisting of 96 children who were referred with suspected hearing loss. They underwent distortion product otoacoustic emissions (DPOAE) testing. Out of 96 children who underwent DPOAE testing, 25 (26.04%) passed the test, 55(57.29%) had "refer" result in bilateral ears whereas 16 (16.67%) had "refer" result in either ear. OAE is a simple, cost-effective and convenient tool for hearing screening in spite of some limitations. Universal new-born hearing screening can be implemented using OAE.


Nigrumin-5-p-coumarate and nigrumin-5-ferulate, two unusual nitrile-containing metabolites from black currant (Ribes nigrum) seed.
Two novel nitrile-containing compounds, nigrumin-5-p-coumarate and nigrumin-5-ferulate, together with six known flavonoids, were isolated from the seed of black currant (Ribes nigrum). The chemical structures of nigrumin-5-p-coumarate and 5-ferulate were elucidated using NMR spectroscopy as 2-trans-p-coumaroyloxymethyl-4-beta-D-glucopyranosyloxy-2(E)-butenenitrile and 2-trans-feruloyloxymethyl-4-beta-D-glucopyranosyloxy-2(E)-butenenitrile, respectively.


Does radial artery harvesting for coronary revascularization cause neurological injury in the forearm and hand?
Radial artery (RA) is now used widely as a conduit of choice in coronary artery bypass grafting. Although RA removal is considered safe in the presence of adequate collateral arterial supply, there is still a considerable suspicion on the functional status of the forearm and hand. However, a neurological dysfunction may occur owing to either surgical trauma or ischemic neuropathy. This study was aimed to investigate the functional outcome of the donor forearm nerves of the patients who underwent coronary artery bypass grafting surgery with RA conduits. A consecutive series of 50 patients who underwent coronary artery bypass graft surgery with one or two RA grafts were investigated in the study. Motor and sensory functions of donor forearm nerves were measured by ENMG studies, pre- and postoperatively at the third week and sixth month of the operation. The conduction velocities, distal latencies and amplitudes of action potentials for motor and sensorial conductions of radial, ulnar and median nerves were measured in each ENMG examination. Neurologic status of the donor forearm and hand was assessed by the same neurologist who performed a detailed neurologic physical examination and ENMG studies. Results were statistically compared using one-way ANOVA test. The incidence of any neurologic symptoms was 32% in early postoperative period. All reported neurologic complaints were associated with sensory conduction deceleration in ENMG investigations of related nerves. In postoperative assessment, median nerve sensory-motor, and ulnar nerve motor conduction records were slightly lower than the preoperative values, but no statistical difference was observed. Pre- and postoperative radial nerve motor and sensory conduction records were statistically similar (P>0.05). We advocate that removal of RA does not lead to any major neurologic hand complications in the presence of adequate collateral arterial blood supply. ENMG studies confirmed minimal conduction alterations with no statistical significance, even if neurologic symptoms were stated.


Partial identification by site-directed mutagenesis of a cell growth inhibitory site on the human galectin-1 molecule.
Previous work, by us and others, has shown that mammalian galectins-1 have a growth-inhibitory activity for mammalian cells which is apparently independent of their beta-galactoside binding site. We have made recombinant human galectin-1 as a bacterial fusion protein with an N-terminal hexahistidine tag. This protein displays both haemagglutination and growth-inhibitory activities, even in the presence of the hexahistidine tag. Site-directed mutagenesis of this protein has confirmed the independent nature of the protein sites responsible for the two biological activities. Mutant proteins were created, which displayed each activity in the absence of the other. Human galectin-1 possesses a growth-inhibitory site, which is not part of the beta-galactoside binding site. A surface loop, comprising amino acid residues 25-30, and joining two internal beta-strands, forms part of the growth-inhibitory site. This region is relatively close to the N-terminus of the protein, and N-terminal substitutions or extensions also affect growth-inhibitory activity. Further experiments will be necessary to fully define this site.


Temporal Sequence of Laryngeal Vestibule Closure and Reopening is Associated With Airway Protection.
Upper esophageal sphincter opening (UESO), and laryngeal vestibule closure (LVC) are two essential kinematic events whose timings are crucial for adequate bolus clearance and airway protection during swallowing. Their temporal characteristics can be quantified through time-consuming analysis of videofluoroscopic swallow studies (VFSS). We sought to establish a model to predict the odds of penetration or aspiration during swallowing based on 15 temporal factors of UES and laryngeal vestibule kinematics. Manual temporal measurements and ratings of penetration and aspiration were conducted on a videofluoroscopic dataset of 408 swallows from 99 patients. A generalized estimating equation model was deployed to analyze association between individual factors and the risk of penetration or aspiration. The results indicated that the latencies of laryngeal vestibular events and the time lapse between UESO onset and LVC were highly related to penetration or aspiration. The predictive model incorporating patient demographics and bolus presentation showed that delayed LVC by 0.1 s or delayed LVO by 1% of the swallow duration (average 0.018 s) was associated with a 17.19% and 2.68% increase in odds of airway invasion, respectively. This predictive model provides insight into kinematic factors that underscore the interaction between the intricate timing of laryngeal kinematics and airway protection. Recent investigation in automatic noninvasive or videofluoroscopic detection of laryngeal kinematics would provide clinicians access to objective measurements not commonly quantified in VFSS. Consequently, the temporal and sequential understanding of these kinematics may interpret such measurements to an estimation of the risk of aspiration or penetration which would give rise to rapid computer-assisted dysphagia diagnosis. 2 Laryngoscope, 133:521-527, 2023.


Mechanisms of antidiarrhoeal activity of methanol leaf extract of Combretum hypopilinum diels (combretaceae): Involvement of opioidergic and (α1 and β)-adrenergic pathways.
The plant Combretum hypopilinum Diels (Combretaceae) is used in traditional medicine for the treatment of diarrhoea and other diseases in Africa. Previously, the antidiarrhoeal activity of its methanol leaf extract was reported. However, the mechanism(s) responsible for this activity is yet to be evaluated. This study aimed to elucidate the possible mechanism(s) of antidiarrhoeal activity of methanol leaf extract of Combretum hypopilinum (MECH) in mice. Phytochemical screening and acute toxicity study were conducted according to standard methods. Adult mice were orally (p.o) administered distilled water (10 ml/kg), MECH (1000 mg/kg) and loperamide (5 mg/kg). The probable mechanisms of antidiarrhoeal activity of MECH were investigated following pretreatment with naloxone (2 mg/kg, subcutaneously), prazosin (1 mg/kg, s.c), yohimbine (2 mg/kg, intraperitoneally), propranolol (1 mg/kg, i.p), pilocarpine (1 mg/kg, s.c) and isosorbide dinitrate (150 mg/kg, p.o) 30 min before administration of MECH (1000 mg/kg). The mice were then subjected to castor oil-induced intestinal motility test. The oral median lethal dose (LD50) of MECH was found to be higher than 5000 mg/kg. There were significant (p < 0.05) decrease in the charcoal movement in the mice treated with the MECH (1000 mg/kg) and loperamide (5 mg/kg). The pretreatment of the mice with naloxone, prazosin and propranolol each significantly (p<0.05) reversed the antidiarrhoeal activity produced by MECH. The results obtained in this study suggest the probable involvement of opioidergic and (α1 and β)-adrenergic systems in the antidiarrhoeal activity of the methanol leaf extract of Combretum hypopilinum.


Vulvar neoplasia in the young.
Vulvar intraepithelial neoplasms may be occurring more frequently among younger age groups. Six patients with carcinoma in situ or severe vulvar dysplasia are reported, as well as one patient with microinvasive carcinoma, all under the age of 30 years. The vulvar lesions were noted to be mostly multicentric. They were associated with other intraepithelial neoplasias of the cervix or vagina in four of the six cases. The lesions were most often mistaken for condyloma acuminatum. Histologic changes were primarily Bowen's disease or Bowenoid dysplasia.


Multiple brain abscesses following esophageal dilation.
A 6-year-old boy esophageal stricture due to the ingestion of caustic 7 months prior to admission. Eight esophageal dilations and a feeding gastrostomy were performed. He presented with seizure, right-sided weakness, fever, and somnolence. Computed tomographic scans revealed multiple brain abscesses. The abscesses were treated by burr-hole drainage. The patient improved and was discharged from the hospital without neurological deficit. Brain abscesses are not very common following esophageal dilation. It should be kept in mind that brain abscess is a potential complication of esophageal dilation.


Escherichia coli phosphoglucose isomerase can be substituted by members of the PGI family, the PGI/PMI family, and the cPGI family.
The Escherichia coli strain Pgi-UdhA, a mutant of the strain MG1655, is deficient in both the pgi gene and the udhA gene and cannot grow on glucose as carbon and energy source. This strain was transformed with different pET-plasmids containing archaeal or bacterial pgi, cpgi or pgi/pmi genes from the three known PGI families (PGI, PGI/PMI, cPGI). Growth could be restored upon plasmid-based expression of pgi, pgi/pmi or cpgi genes indicating that these heterologous proteins can substitute for E. coli PGI. However, complete restoration of the growth rate could not be obtained by any of the PGIs, PGI/PMIs, or cPGIs used. The data indicate that the PGI function of the three PGI families is functionally exchangeable in glycolysis.


Different forms of childhood maltreatment have different impacts on the neural systems involved in the representation of reinforcement value.
The current study aimed to address two gaps in the literature on child maltreatment, reinforcement processing and psychopathology. First, the extent to which compromised reinforcement processing might be particularly associated with either neglect or abuse. Second, the extent to which maltreatment-related compromised reinforcement processing might be associated with particular symptom sets (depression, conduct problems, anxiety) or symptomatology more generally. A sample of adolescents (N = 142) aged between 14 and 18 years with varying levels of prior maltreatment participated in this fMRI study. They were scanned while performing a passive avoidance learning task, where the participant learns to respond to stimuli that engender reward and avoid responding to stimuli that engender punishment. Maltreatment (abuse and neglect) levels were assessed with the Childhood Trauma Questionnaire (CTQ). We found that: (i) level of neglect, but not abuse, was negatively associated with differential BOLD responses to reward-punishment within the striatum and medial frontal cortex; and (ii) differential reward-punishment responses within these neglect-associated regions were particularly negatively associated with level of conduct problems. Our findings demonstrate the adverse neurodevelopmental impact of childhood maltreatment, particularly neglect, on reinforcement processing. Moreover, they suggest a neurodevelopmental route by which neglect might increase the risk for conduct problems.


Fifty-Hertz electromagnetic fields facilitate the induction of rat bone mesenchymal stromal cells to differentiate into functional neurons.
Research results have shown that bone mesenchymal stromal cells (BMSC) can different into neural cells. Electromagnetic fields (EMF) play a role in regulating cell proliferation and differentiation, but the mechanisms behind this are unknown. In the present study, we explored the efficacy of EMF on the induction of rat BMSC differentiation into neurons in vitro. First, rat BMSC were induced in a nerve cell culture environment and divided into three groups: an EMF induction treatment group (frequency of 50 Hz, magnetic induction of 5 mT, 60 min per day for 12 days), an induction-only group and a control group. Second, we observed cell phenotypes in a confocal microscope, tested gene expression through the use of reverse transcriptase-polymerase chain reaction, and detected postsynaptic currents by means of a cell patch-clamp. We analyzed the cell cycles and the portion of cells expressing neural cell markers with the use of flow cytometry. The results indicated that EMF can facilitate BMSC differentiation into neural cells, which expressed neuronal-specific markers and genes; they formed synaptic junctions and pulsed excitatory postsynaptic currents. At the same time, the G0-G1 phase ratio recorded by means of flow cytometry gradually decreased under the EMF treatment, whereas there was an increase of S-phase ratio, and the portion of cells expressing neuronal-specific markers increased. Given that a noninvasive treatment of 50-Hz EMF could significantly facilitate BMSC to differentiate into functional neurons, EMF appears to be a promising clinical option for stem cell transplantation therapies to combat central nervous system diseases.


Immunobiology of HPV and HPV vaccines.
Genital human papillomavirus (HPV) infection with both low- and high-risk types is common, but most infections resolve as a result of a cell-mediated immune response. Failure to induce an effective immune response is related to inefficient activation of innate immunity and ineffective priming of the adaptive immune response; this defective immune response facilitates viral persistence, a key feature of high-risk HPV infection. This milieu becomes operationally HPV antigen tolerant, and the host's defenses become irrevocably compromised. HPV antigen-specific effector cells are poorly recruited to the infected focus and their activity is downregulated; neoplastic HPV containing cervical keratinocytes expressing high levels of E6 and E7 oncoproteins are not killed in this immunosuppressive, tolerant milieu, and progression to high-grade disease and cancer can result. Highly efficacious prophylactic HPV L1 virus-like particle (VLP) vaccines circumvent viral epithelial evasion strategies since they are delivered by intramuscular injection. The stromal dendritic cells of the muscle that encounter the highly immunogenic repeat structure of the VLP then migrate with their cargo to the lymph node, initiating an immune cascade that results in a robust T-cell dependent B-cell response, which generates high levels of L1-specific serum neutralizing antibodies and immune memory.


Summer dispersal and survival of juvenile Great Tits in southern Sweden.
Movements and survival of 506 first-brood Great Tit nestlings that fledged in mid-June in an oak wood in southern Sweden were studied by intensive trapping in that wood and in several neighbouring woods between 17 July and 10 September 1977. A total of 1177 captures of 508 individuals was made.Two periods of summer dispersal can be distinguished: the first period, one to one- and-one-half months after fledging, lasts longer in females and results in females moving farther away from their birthplace than males; and the second period in early September. There was no effect of brood-size, fledging date or size on dispersal movements. There is, however, a 'nest effect' in that siblings tend to be more alike in the distance moved than non-siblings.The summer mortality rate is constant but high (13% per week). It is not affected by brood size or fledging date, but during the first month after fledging large individuals survive better than smaller ones. The summer mortality rate of dispersers (birds moving between woods) is not higher than that of non-dispersers.The results contradict two hypotheses proposed to explain when and how postfledging mortality occurs. The mortality rate is not higher during the first month after fledging, as Perrins' and Lack's hypothesis predicts. Since only 22% of the young are still alive at the beginning of September, autumn territorial behaviour cannot be the main factor causing juvenile losses, as proposed by Kluyver.There is some circumstantial evidence that Great Tits compete for food during the summer, and that food therefore could be in short supply, as suggested by Perrins.The observed differential dispersal of adults and young, and of male and female juveniles, may be the result of the dominance relationships in the family flock and later in the summer flocks, with subordinate individuals moving farthest.


An ELISA for grancalcin, a novel cytosolic calcium-binding protein present in leukocytes.
Grancalcin is a newly discovered cytosolic calcium-binding protein, belonging to the group of EF-hand proteins. Grancalcin is specifically associated with cells originating in the bone marrow. Grancalcin binds reversibly to secretory vesicles and plasma membranes in human neutrophils and might therefore play a role in the regulation of vesicle/granule exocytosis. We describe here the production of recombinant grancalcin, the generation of antibodies to the protein and the development of a specific, accurate and sensitive ELISA for the detection of human leukocytic grancalcin. This ELISA may be useful for monitoring leukocyte infiltration into tissues.


Solution-state behaviour of algal mono-uronates evaluated by pure shift and compressive sampling NMR techniques.
Sodium salts of the algal uronic-acids, d-mannuronic acid (HManA) and l-guluronic acid (HGulA) have been isolated and characterised in solution by nuclear magnetic resonance (NMR) spectroscopy. A suite of recently-described NMR experiments (including pure shift and compressive sampling techniques) were used to provide confident assignments of the pyranose forms of the two uronic acids at various pD values (from 7.5 to 1.4). The resulting high resolution spectra were used to determine several previously unknown parameters for the two acids, including their pKa values, the position of their isomeric equilibria, and their propensity to form furanurono-6,3-lactones. For each of the three parameters, comparisons are drawn with the behaviour of the related D-glucuronic (HGlcA) and D-galacturonic acids (HGalA), which have been previously studied extensively. This paper demonstrates how these new NMR spectroscopic techniques can be applied to better understand the properties of polyuronides and uronide-rich macroalgal biomass.


Poly (ADP-ribose) polymerase, a potential target for drugs: Part II. Regulation of differentiation by the poly ADP-ribose system.
It is shown that eukaryotic differentiation is specifically sensitive to pADPRT regulation in Trypanosomna, Leishmania and Mytilus models. There is powerful inhibition of early differentiation without cell toxicity by pADPRT ligands.


Long-term effects of tacrolimus for maintenance therapy of lupus nephritis: a 5-year retrospective study at a single center.
Previously, we reported the short-term effects of tacrolimus in treating lupus nephritis (LN); however, long-term data are lacking. We conducted a retrospective study of 26 adult patients with LN. Tacrolimus was initiated at a dose of 3 mg/day after induction therapy. We retrospectively collected data on renal response; modified lupus nephritis disease activity index (m-LNDAI), including hematuria, proteinuria, complement 3, anti-double-stranded DNA antibody, and estimated glomerular filtration rate (eGFR); and prednisolone (PSL) dose. Three patients discontinued tacrolimus treatment because of related complications, including acute myeloblastic leukemia, tremor, or a general personal choice or a desire to become pregnant. We analyzed data from 23 patients who were treated with tacrolimus over a 5-year period. The mean urinary protein/creatinine ratio decreased from a baseline of 0.24 (min 0.00-max 4.20) to 0.00 (0.00-7.05) at 5 years (p = 0.0134), while eGFR levels remained unchanged throughout the 5 years. The mean m-LNDAI decreased from a baseline of 3.00 (0.00-12.0) to 2.00 (0.00-4.00) at 5 years (p = 0.0074). The mean PSL dose decreased from a baseline of 0.33 (0.00-0.75) mg/kg/day to 0.15 (0.15-0.33) at 5 years (p = 0.001). Our results suggest that tacrolimus is potentially effective for treating LN and that the current dosage was generally well tolerated for long-term maintenance treatment in our patients with LN.


Descriptive Morphology of Male and Female Genitalia of the Long-horned Grasshopper in the Tribe Aphractini (Orthoptera: Tettigoniidae), with a Key to the Genera.
The male and female genital morphologies of the tribe Aphractini are presented in this study. Four species are included: Aphractus acuminatus, Paraphractus abbreviatus, Polycleptidella chilensis and Polycleptis scutellifera. A dichotomous key to the genera is provided. The lengths between the female spermathecal duct and titillatory articulated processes are similar within species but differ between them. Therefore, we propose that the function of these organs could be associated with the sperm removal strategy.


Crystal structure of phosphoglucomutase from Leishmania major at 3.5 Å resolution.
The crystal structure of phosphoglucomutase (LmPGM) from the parasite Leishmania major has been solved at 3.5 Å resolution. Although the active form of the enzyme is monomeric in solution, four molecules (A, B, C, D) were found in the asymmetric unit, of which the pairs (A,D) and (B,C) were of identical inter-subunit geometry. The parasitic enzyme constituted of four domains exhibited the canonical 'heart' shape of the protein, with domains I to III having a conserved α|β core, while the fourth (IV) domain being structurally distinct from the rest. Conformational variability of the IVth domain, postulated to be responsible for the catalytic function of the enzyme has been studied by normal mode analysis (NMA) and the conformational features responsible for domain movement in the 'hinge region' analyzed in detail. Although the active site of phosphoglucomutase is highly conserved from parasite to human, initial calculations show that a ligand binding pocket could exist near the hinge region, which is unique to the parasite. The enzymatic parameters of LmPGM have been determined and compared with other PGMs from orthologous species in addition to elucidating its mechanism of action by docking the substrate, intermediate onto the active site.


Spermometer: electrical characterization of single boar sperm motility.
To study single sperm boar motility using electrical impedance measurements in a microfluidic system. Comparison of the optical data and electrical impedance data. Research laboratory at a university. Boar semen sample were used. A microfluidic system is developed that is able to spatially confine single boar sperm cells and allows noninvasive analysis of their motility on the single cell level. Using this system, the single sperm motility was affected by changing the temperature or adding chemical stimuli (caffeine). The retrieved electrical impedance and video data were processed using Matlab. The sperm beat frequency and amplitude determined from the electrical impedance and video data. The electrically measured sperm beat frequency was verified by optical analysis and in correspondence. Furthermore the microfluidic platform allowed single sperm analysis by altering the sperm by temperature and chemical stimuli. This platform could be exploited as a potential tool to study sperm cells on the single cell level and to perform advanced sperm selection for intracytoplasmic sperm injection (ICSI) applications.


Trophic transfer of Cd from larval chironomids (Chironomus riparius) exposed via sediment or waterborne routes, to zebrafish (Danio rerio): tissue-specific and subcellular comparisons.
Zebrafish were fed chironomid larvae (8% wet weight daily ration) for 7 days, followed by 3 days of gut clearance in a static-renewal system. Regardless of whether the chironomids had been loaded with Cd via a waterborne exposure or sediment exposure, they had similar subcellular distributions of Cd, with the largest areas of storage being metal rich granules (MRG)>organelles (ORG)>enzymes (ENZ) except that sediment-exposed chironomids had significantly more Cd in the metallothionein-like protein (MTLP) fraction, and significantly less Cd in the cellular debris (CD) fraction. When zebrafish fed sediment-exposed chironomids (153+/-11 microg Cd/g dry weight) were compared directly to zebrafish fed waterborne exposed chironomids (288+/-12microg Cd/g dry weight), identical whole-body Cd levels were observed, despite the difference in the concentration in the food source. Thus trophic transfer efficiency (TTE) of Cd was significantly greater from sediment-exposed chironomids (2.0+/-0.5%) than from waterborne-exposed chironomids (0.7+/-0.2%). Subsequent tests with waterborne exposed chironomids loaded to comparable Cd concentrations, as well as with Cd-spiked manufactured pellets, demonstrated that TTEs were concentration-independent. In all treatments, zebrafish exhibited similar subcellular storage of Cd, with the greatest uptake occurring in the ORG fraction followed by the ENZ fraction. However, neither trophically available metal (TAM) nor metabolically available fractions (MAF) were good predictors for the TTEs found in this study. Tissue Cd concentrations were highest in the kidney and gut tissue, then liver, but lower in the gill, and carcass. Overall, the gut and carcass contributed >/=71% to total body burdens on a mass-weighted basis. This study presents evidence that Cd may be acquired by fish from natural diets at levels of environmental relevance for contaminated sites, and that the exposure route of the prey influences the TTE.


Accelerated onset and delayed recovery of d-tubocurarine blockade with pancuronium in infants and children.
The effect of age on the onset and duration of action of a d-tubocurarine (DTC) neuromuscular blockade with and without pancuronium priming in children was examined. Sixty ASA physical status I or II patients in three age ranges (0-1 yr, 1-3 yr and 3-10 yr) were anaesthetized with thiopentone, halothane and nitrous oxide. Each patient received either a single paralyzing dose of DTC 0.4 mg.kg-1, or DTC 0.36 mg.kg-1 preceded three minutes earlier by pancuronium 0.007 mg.kg-1. Evoked force of contraction of the adductor pollicis was measured using train-of-four stimulation applied every 12 sec. Time to 90 per cent first twitch depression after a single dose of DTC increased with increasing age (r = 0.65, p less than 0.01), and was 1.6 min (SEM +/- 0.3) in the 0-1 yr group, 1.9 +/- 0.3 min (1-3 yr), and 5.2 +/- 1.2 min (3-10 yr). Time to ten per cent spontaneous recovery after single dose DTC was shorter in older individuals (r = 0.40, p less than 0.05), being 36.4 +/- 5.1 min in infants 0-1 yr, 30.6 +/- 4.6 min (1-3 yr), and 24.0 +/- 2.7 min (3-10 yr). Priming with pancuronium accelerated the onset significantly in all age groups with 90 per cent T1 depression occurring at 0.7 +/- 0.1 min (0-1 yr), 0.9 +/- 0.1 min (1-3 yr), and 2.1 +/- 0.6 min (3-10 yr). However, priming delayed recovery, especially in infants.(ABSTRACT TRUNCATED AT 250 WORDS)


Interactions of porphyrins with purified DNA and more highly organized structures.
Studies of the solution properties of gold(III)tetrakis(4-N-methylpyridyl) porphine and its DNA binding characteristics have been conducted utilizing uv/vis absorption spectroscopy, circular dichroism (CD), Mossbauer spectroscopy, and temperature-jump relaxation techniques. These studies indicate that over the concentration range considered this water soluble gold(III) porphyrin does not aggregate, binds axial ligands only weakly with a preference for soft Lewis bases, and is capable of intercalation into nucleic acids of appropriate base pair content. The interaction of this and several other porphyrins with the synthetic polynucleotide poly(dA-dC).poly(dT-dG) has been studied. Spectroscopic signatures for intercalation were found for those derivatives not having axial ligands. Intercalation into chromatin in vitro can also occur with those porphyrins and metalloporphyrins which do not have axial ligands. Finally, studies utilizing microinjection techniques indicate that once within the cell, tetrakis(4-N-methylpyridyl)porphine tends to localize in the nucleus.


Numbers of neurotensin-immunoreactive neurons selectively increased in rat ventral striatum following acute haloperidol administration.
The effect of haloperidol (HAL) on neurotensin (NT) levels in various structures of the rat brain was evaluated using an immunoperoxidase method. Adult, male Sprague-Dawley rats were given intraperitoneal injections of either HAL (2 mg/kg) or vehicle at twenty-four and four hours prior to sacrifice. The brains were fixed, cut at 50 micron on the vibratome, and prepared to demonstrate NT immunoreactivity, or its absence following appropriate control incubations. The distributions of NT-immunoreactive (IR) cell bodies were plotted using the camera lucida, and the numbers of NT-IR neurons in various structures were recorded. The numbers of NT-IR perikarya in striatal and ventral striatal structures of HAL-treated rats greatly exceeded those observed in the same structures of control animals. In other NT-IR rich regions including the bed nucleus of the stria terminalis, central amygdala, hypothalamus and septum, HAL and control values did not differ. Conversely, HAL treatment appeared to effect a decrease in the number of immunoreactive perikarya in the medial amygdala and caudal part of the endopiriform area. It was noted that in brain regions where D-2 receptors are reported to be numerous, the number of NT-stained cells increased following HAL treatment, whereas in regions where D-1 receptors predominate, the number remained stable or decreased. Subjective evaluation of axon terminal immunoreactivity revealed a change only in the globus pallidus, where the proportional area of that structure exhibiting NT-immunoreactivity expanded following HAL.


Shaping innovation in health care: A content analysis of innovation policies in the English NHS, 1948-2015.
Governments around the world seek to design policies that enhance the innovative capacity of public service. Hence, identifying the underlying meanings attributed to innovation concepts in public policies is critical, as these very understandings inform not only the policy discourses, but also the overall institutional landscape regulating innovation activities. This paper examines such fundamental definitional aspects in the specific context of the National Health Service in England. For this purpose, it traces the evolution of the innovation concept in policy discourse based on the analysis of 21 key policy documents published or commissioned by the English Department of Health between 1948 and 2015. Systematic analysis of these texts reveals that policymakers' conception of healthcare innovation broadened considerably over time. English health innovation policy initially focused on basic biomedical research. Subsequently, it entered a transitional period, zeroing in on science- and technology-based innovation. Finally, this focus gradually shifted to a broader conception of innovation translating into health, economic, and service design benefits.


Extracorporeal membrane oxygenation for pediatric cardiopulmonary failure.
Extracorporeal membrane oxygenation is now standard treatment of severe respiratory failure in newborn infants in our center (200 cases) and worldwide (over 2500 cases), but there are few reports of such trials in older children. We reviewed our experience with extracorporeal membrane oxygenation in 33 children aged 1 week to 18 years between 1971 and 1989. The modality was used when all other treatment failed. Extracorporeal membrane oxygenation provided excellent cardiopulmonary support for 1 to 25 days (average 7 1/2 days). The survival rate was 25% for cardiac support patients and 47% for respiratory failure patients (36% overall survival). Mechanical complications included membrane lung failure, tubing rupture, and pump failure, all managed without mortality. Physiologic complications included bleeding, pneumothorax, cardiac arrest, renal failure, hepatic failure, and brain injury. The major cause of death was irreversible injury to lung, heart, or brain. Extracorporeal life support is a reasonable approach for children with serious but reversible cardiopulmonary failure.


Short-term testing of heart rate variability in heart-transplanted children: equal to 24-h ECG recordings?
Heart rate variability (HRV) is reduced in adults and children after cardiac transplantation. Testing of HRV has been used to assess re-innervation of the cardiac graft; its reliability in ruling out acute graft rejection is still under investigation. This study used a short-term test on HRV in 23 heart and heart-lung transplanted children and adolescents and compared the results with 24-h ECG recordings. Twenty-three subjects (16.3+/-4.2 yr; 10 females) underwent a 10-min HRV test at two occasions and one 24-h ECG. HRV was calculated according to the time domain method (RR interval, standard deviation of RR interval) and the frequency domain method (total power, LF and HF for assessment of sympathovagal modulation of heart rate). Correlation between the short-term tests and 24-h ECG was high with regard to the frequency domain analysis of HRV. Correlation was less pronounced in the time domain method. In heart and heart-lung-transplanted children and adolescents, due to reduced overall HRV short-term testing may give as reliable data as 24-h ECG. Therefore, especially when power spectral analysis has to be performed as a longitudinal assessment of re-innervation of the cardiac graft, short-term testing may offer an easily applicable and non-invasive diagnostic tool. Further studies are warranted to investigate whether HRV testing may contribute to rule out acute graft rejection.


Isolation of a multi-trait plant growth promoting Brevundimonas sp. and its effect on the growth of Bt-cotton.
Arid regions pose a serious problem for crop production by suppressing plant growth. The use of plant growth promoting rhizobacteria (PGPR) as bioinoculant may be promising to enhance the crop yield in arid conditions. In the present investigation, four strains of cultivable bacteria associated with the rhizosphere of Saccharum L. grown in arid region were isolated using N-free media. Assessment of their nitrogen-fixing ability through amplification of nifH gene showed the presence of nifH gene (390 bp) in only one (MDB4) of the four isolates. The nitrogen-fixing potential of this isolate was confirmed by the presence of nitrogenase activity determined using acetylene reduction assay. The diazotrophic MDB4 isolate also exhibited other PGPR traits, such as the production of indole-3-acetic acid (IAA) and ammonia. In pot experiments, inoculation of Bt-cotton seeds with MDB4 enhanced the growth of plants as shown by significant increase in plant height (68.41 %), shoot dry weight (58.44 %) and root dry weight (64.81 %) over untreated control. The MDB4 strain was Gram negative and identified as Brevundimonas sp. on the basis of phenotypic, biochemical, phylogenetic and 16S rRNA gene sequencing data. It is concluded that the MDB4 bacterial strain having different plant growth promoting activities can be considered as a beneficial microbe for sustainable agriculture in arid regions.


Experimental design for the optimization of the extraction conditions of polycyclic aromatic hydrocarbons in milk with a novel diethoxydiphenylsilane solid-phase microextraction fiber.
An innovative solid-phase microextraction coating based on the use of diethoxydiphenylsilane synthesized by sol-gel technology was used for the determination of polycyclic aromatic hydrocarbons at trace levels in milk. The effects of time and temperature of extraction and acetone addition were investigated by experimental design. Regression models and desirability functions were applied to find the experimental conditions providing the highest global extraction response. The capabilities of the developed fiber were proved obtaining limit of quantitation values in the low microg/l range, enabling the direct analysis of complex matrices like milk and a complete desorption of high-boiling compounds without carryover effects.


Is morphine-induced akinesia related to inhibition of reflex activation of flexor alpha-motoneurones? Role of the nucleus accumbens.
Unilateral injections of morphine (5-15 micrograms) into the nucleus accumbens of non-anesthetized rats produces a decrease of locomotor activity and a catalepsy. In a similar dose-response relationship, injections of morphine into this area inhibited the reflex activation of alpha-motoneurones by mild tetanic stimulation of the ipsilateral peroneal nerve (flexor alpha-motoneurones) in halothane-anesthetized rats. All these effects were antagonized by systemic administration of naloxone. Our results suggest that a reduction in reflex activation of flexor alpha-motoneurones by proprioceptive stimuli seems to be relevant for the development and/or mediation of akinesia and catalepsy, and that the nucleus accumbens plays a key role in these effects produced by morphine.


Slow programmable and ultra-rapid freezing of human embryos.
To compare the outcomes of slow freezing with ultra-rapid freezing (URF) of cleavage-stage human embryos on aluminum foil. Two-cell mouse embryos were used to test our method of ultra-rapid freezing. The embryos were randomly allocated to a non-frozen control (208 embryos), and slow (204 embryos) or ultra-rapid freezing groups (204 embryos). Immediate survival rate, further cleavage and blastocyst formation were compared. After validating our ultra-rapid freezing method on mouse embryos, we applied a similar ultra-rapid freezing protocol to human embryos. Consecutive human frozen/thawed embryo transfer (FET) cycles from October 1998 to June 2005 were reviewed. The survival rate, further cleavage rate and the pregnancy outcomes were compared between the URF and slow programmable freezing. Mouse embryos in the URF group survived the freezing/thawing process better than those in the slow freezing group (93.1% vs 82.8%, P = 0.001). Blastocyst and hatching blastocyst formation of the surviving embryos were comparable in the URF and slow freezing group (59% vs 58.6%, P = 0.944 and 32.6% vs 42%, P = 0.066, respectively). There were 146 human FET cycles in the URF group and 28 cycles in the slow freezing group. The immediate survival of embryos was higher in the URF group than in the slow freezing group (87.9% and 64.3%, P < 0.001). There was no significant difference in the mean number of embryos per transfer (3.7 +/- 1.3 and 3.3 +/- 1.2, P = 0.178), clinical pregnancy rate per transfer (28.5% and 21.4%, P = 0.444) and implantation rate per embryo (10.98% and 10.9%, P = 0.974) in the URF or slow freezing groups. Our in-house URF method gave comparable results to slow programmable freezing. Although the risk of potential contamination is a major drawback of the present ultra-rapid freezing technique, future refinement will minimize or entirely eliminate this concern.


The PMMA epidemic in Norway: comparison of fatal and non-fatal intoxications.
During a 6 month period (July 2010-January 2011) we observed 12 fatal intoxications and 22 non-fatal cases related to the drug paramethoxymethamphetamine (PMMA) in Norway (4.8 mill inhabitants). This toxic designer drug, also known as "Death", is occasionally found in street drugs offered as "ecstasy" or "amphetamine". The present study aimed to evaluate the cause of death, and to compare the PMMA blood concentrations in fatal and non-fatal cases. Methods for identification and quantification of PMMA are presented. The median age of fatalities was 30 years (range 15-50) with 67% males; in non-fatal cases 27 years (20-47) with 86% males. In the 12 fatalities, the median PMMA blood concentration was 1.92 mg/L (range 0.17-3.30), which is in the reported lethal range of 0.6-3.1 mg/L in peripheral blood and 1.2-15.8 mg/L in heart blood. In the 22 non-fatal cases, the median PMMA concentration was 0.07 mg/L (range 0.01-0.65). Poly-drug use was frequent both in fatal and non-fatal cases. The PMA concentrations ranging from 0.00 to 0.26 mg/L in both groups likely represented a PMMA metabolite. Three fatalities were attributed to PMMA only, six to PMMA and other psychostimulant drugs, and three to PMMA and CNS depressant drugs, with median PMMA concentrations of 3.05 mg/L (range 1.58-3.30), 2.56 (1.52-3.23) and 0.52 mg/L (0.17-1.24), respectively. Eight victims were found dead, while death was witnessed in four cases, with symptoms of acute respiratory distress, hyperthermia, cardiac arrest, convulsions, sudden collapse and/or multiple organ failure. In summary, all fatalities attributed to PMMA had high PMMA blood concentrations compared to non-fatal cases. Our sample size was too small to evaluate a possible impact of poly-drug use. A public warning is warranted against use and overdose with illegal "ecstasy" or "speed" drugs.


Multiscale investigation of USPIO nanoparticles in atherosclerotic plaques and their catabolism and storage in vivo.
The storage and catabolism of Ultrasmall SuperParamagnetic Iron Oxide (USPIO) nanoparticles were analyzed through a multiscale approach combining Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM) at different times after intravenous injection in an atherosclerotic ApoE(-/-) mouse model. The atherosclerotic plaque features and the USPIO heterogeneous biodistribution were revealed down from organ's scale to subcellular level. The biotransformation of the nanoparticle iron oxide (maghemite) core into ferritin, the non-toxic form of iron storage, was demonstrated for the first time ex vivo in atherosclerotic plaques as well as in spleen, the iron storage organ. These results rely on an innovative spatial and structural investigation of USPIO's catabolism in cellular phagolysosomes. This study showed that these nanoparticles were stored as non-toxic iron compounds: maghemite oxide or ferritin, which is promising for MRI detection of atherosclerotic plaques in clinics using these USPIOs. From the Clinical Editor: Advance in nanotechnology has brought new contrast agents for clinical imaging. In this article, the authors investigated the use and biotransformation of Ultrasmall Super-paramagnetic Iron Oxide (USPIO) nanoparticles for analysis of atherosclerotic plagues in Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM). The biophysical data generated from this study could enable the possible use of these nanoparticles for the benefits of clinical patients.


Screening for Epstein-Barr and human cytomegalovirus in normal and abnormal cervical smears by fluorescent in situ cytohybridization.
Using the routine Papanicolaou test for grouping, 35 normal and 148 abnormal cervical smears were screened by fluorescent in situ cytohybridization for Epstein-Barr (EBV) and human cytomegalovirus (HCMV). Viral presence was detected in 55% of all hybridized smears while routine Papanicolaou tests exposed no morphological evidence for HCMV or EBV. Thus in situ cytohybridization is necessary and suitable for direct identification of EBV and HCMV. The prevalence of viral infection for women with normal cervical smears was 29% for HCMV and 34% for EBV. Even smears of three of the four virgins were positive for HCMV and two had a mixed infection with EBV. The infection rate with at least one of these two herpesviruses was 51% in the control group, 56% in smears with reactive and reparative cell changes, 54% in mild (slight) dysplasias and 56% in moderate or severe dysplasias. Thus infection with HCMV and EBV did not differ significantly in controls and prevention groups. Both viruses were most frequently found in the age group 20 to 29 years. These data suggest that HCMV and EBV are not involved in the etiology of intraepithelial neoplasias and carcinomas of the uterine cervix.


Coronary artery calcification and emphysema.
It is thought that emphysema patients are at a higher risk of coronary artery disease. The present study is one of very few that evaluated the prevalence of significant coronary artery disease in emphysema patients using coronary artery calcification measured by electron beam computed tomography. A retrospective chart review evaluated 1720 consecutive patients, some of whom were self-referred. All patients had both heart and lungs imaged with electron beam computed tomography when they were seen at the Inner Imaging Center, a cardiac imaging center affiliated with the Beth Israel Hospital in New York, New York. Multiple logistic regression was performed to determine which factors were independently associated with coronary artery calcification. Age, sex, hypertension and smoking were the risk factors independently associated with coronary artery calcification in the population studied. The emphysema group was significantly higher on measures of smoking and hypertension compared with the control group. Comparison of scores between the two groups using different categories for coronary artery calcification scores did not show a statistically significant difference using chi(2) analysis (P=0.088). However, there was a significant difference between dichotomized coronary artery calcification scores of lower than 100 and 100 or higher in patients with and without emphysema, respectively (P=0.013). Coexisting smoking and hypertension may contribute to the higher incidence of coronary artery calcification in emphysema patients. Symptoms of chest pain and shortness of breath were not different between the emphysema and control groups. Emphysema patients have a higher prevalence of significant coronary artery calcification, defined as a coronary artery calcification score higher than 100.


Acute Q fever in an Omani presenting with a febrile movement disorder - A Case Report.
Q fever is a zoonotic infection caused by the organism Coxiella burnetii. It is transmitted by contracting the organism from it is most known reservoirs which include cattle, sheep, and goats. It is an endemic disease with very few cases reported in the Arabian Peninsula. It can present with a wide range of clinical presentations; however, the neurological manifestation of Q fever is rare and overlooked hence we present a case report of a 38-year-old man who presented with fever, headache, and jerky movements. He had a significant exposure to livestock animals mainly goats and sheep. The work up was negative apart from positive Coxiella burnetii serology and serum PCR suggestive of acute Q fever. He had shown remarkable improvement after a course of antimicrobial therapy with complete resolution of fever and neurological symptoms. Our case report highlights the importance considering Q fever as a cause of unusual neurological symptoms in Q fever endemic areas and patients with a significant zoonotic exposure.


Evolution of serum prealbumin, C-reactive protein, and orosomucoid in neonates with bacterial infection.
The simultaneous changes in serum prealbumin, orosomucoid (alpha-acidglycoprotein, AGP), and C-reactive protein (CRP) were evaluated in 36 newborn infants with septicemia (n = 20), meningitis (n = 10), arthritis (n = 5), and peritonitis (n = 1). In 29 patients with a favorable outcome the values for serum prealbumin and CRP showed a rapid return toward normal: in 2 to 3 days serum prealbumin increased by 84% from the basal value and remained at (mean +/- 1 SD) 0.11 +/- 0.02 gm/L. Serum CRP decreased from 85 +/- 75 mg/L (range 0.15 to 206 mg/L) to 49 +/- 64 mg/L (2 to 210 mg/L) at 3 to 4 days of evolution and to normal values at day 13 to 16. The changes in serum orosomucoid values were slower, from 1.33 +/- 0.75 gm/L to 1.16 +/- 0.75 gm/L at day 13 to 16, with normalization after 20 to 30 days. Serum orosomucoid values returned to the normal range with the clinical improvement. In some patients the orosomucoid/prealbumin ratio decreased earlier than the serum orosomucoid concentration. Seven patients died, and in four of these in whom at least three values could be determined serum CRP and orosomucoid remained very high, whereas serum prealbumin did not increase or subsequently decreased. These data show an inverse change in serum CRP and prealbumin concentrations in infected neonates. The immediate decrease in CRP reflects the effect of treatment, whereas the later decrease in serum AGP parallels the clinical course of the infection. Thus the determination of these proteins can help to guide the treatment of infection in newborn infants.