A 3-month age difference profoundly alters the primary rat stromal vascular fraction phenotype.
The stromal vascular fraction (SVF) is a heterogeneous population obtained from collagenase digestion of adipose tissue. When cultured the population becomes more homogeneous and the cells are then termed adipose stromal/stem cells (ASCs). Both the freshly isolated primary SVF population and the cultured ASC population possess regenerative abilities suggested to be mediated by paracrine mechanisms mainly. The use of ASCs and SVF cells, both in animal studies and human clinical studies, has dramatically increased during recent years. However, more knowledge regarding optimal donor characteristics such as age is demanded. Here we report that even a short age difference has an impact on the phenotype of primary SVF cells. We observed that a 3-month difference in relatively young adult rats affects the expression pattern of several mesenchymal stem cell markers in their primary SVF. The younger animals had significantly more CD90+/CD44+/CD29+/PDGFRα+primary cells, than the aged rats, suggesting an age dependent shift in the relative cell type distribution within the population. Taken together with recent studies of much more pronounced age differences, our data strongly suggest that donor age is a very critical parameter that should be taken into account in future stem cell studies, especially when using primary cells.


Early activation of rat skeletal muscle IL-6/STAT1/STAT3 dependent gene expression in resistance exercise linked to hypertrophy.
Cytokine interleukin-6 (IL-6) is an essential regulator of satellite cell-mediated hypertrophic muscle growth through the transcription factor signal transducer and activator of transcription 3 (STAT3). The importance of this pathway linked to the modulation of myogenic regulatory factors expression in rat skeletal muscle undergoing hypertrophy following resistance exercise, has not been investigated. In this study, the phosphorylation and nuclear localization of STAT3, together with IL-6/STAT3-responsive gene expression, were measured after both a single bout of resistance exercise and 10 weeks of training. Flexor Digitorum Profundus muscle samples from Wistar rats were obtained 2 and 6 hours after a single bout of resistance exercise and 72 h after the last bout of either 2, 4, or 10 weeks of resistance training. We observed an increase in IL-6 and SOCS3 mRNAs concomitant with phosphorylation of STAT1 and STAT3 after 2 and 6 hours of a single bout of exercise (p<0.05). STAT3-dependent early responsive genes such as CyclinD1 and cMyc were also upregulated whereas MyoD and Myf5 mRNAs were downregulated (p<0.05). BrdU-positive satellite cells increased at 2 and 6 hours after exercise (p<0.05). Muscle fiber hypertrophy reached up to 100% after 10 weeks of training and the mRNA expression of Myf5, c-Myc and Cyclin-D1 decreased, whereas IL-6 mRNA remained upregulated. We conclude that the IL-6/STAT1/STAT3 signaling pathway and its responsive genes after a single bout of resistance exercise are an important event regulating the SC pool and behavior involved in muscle hypertrophy after ten weeks of training in rat skeletal muscle.


[Predictive factors in the bipolarization of depressive disorders].
Since 1966 maniac-depressive illness has been divided into bipolar disorder (BP) and unipolar disorder (UP). Both groups are still in the process of subtyping (bipolar I,II,III and the tentative subtyping of unipolar group by Winokur). When affective disorder begins with depressive episodes is it possible to predict future mania and anticipate BP diagnosis? Are they variables of good predicting value for bipolarization? The issue is of importance since handicap, evolution, prognosis, treatment are somewhat different for UP and BP. Several studies indicate some possible predictors of bipolarization: pharmacological mania, bipolar familial antecedents, postpartum first episode, hypersomnia and psychomotor retardation, psychotic depression, etc. Special attention is given to switch to mania during antidepressant treatment.


Potential Lifshitz transition at optimal substitution in nematic pnictide Ba1-xSrxNi2As2.
BaNi2As2 is a structural analog of the pnictide superconductor BaFe2As2, which, like the iron-based superconductors, hosts a variety of ordered phases including charge density waves (CDWs), electronic nematicity, and superconductivity. Upon isovalent Sr substitution on the Ba site, the charge and nematic orders are suppressed, followed by a sixfold enhancement of the superconducting transition temperature (Tc). To understand the mechanisms responsible for enhancement of Tc, we present high-resolution angle-resolved photoemission spectroscopy (ARPES) measurements of the Ba1-xSrxNi2As2 series, which agree well with our density functional theory (DFT) calculations throughout the substitution range. Analysis of our ARPES-validated DFT results indicates a Lifshitz transition and reasonably nested electron and hole Fermi pockets near optimal substitution where Tc is maximum. These nested pockets host Ni dxz/dyz orbital compositions, which we associate with the enhancement of nematic fluctuations, revealing unexpected connections to the iron-pnictide superconductors. This gives credence to a scenario in which nematic fluctuations drive an enhanced Tc.


Large endocervical polyp with cartilaginous and osseous metaplasia: a hitherto unreported entity.
The author reports a previously unrecognized entity of cervical polyp with cartilaginous and osseous metaplasia. A 57-year-old woman (gravida 0, para 0) was admitted to the hospital because of genital bleeding. A colposcopic examination revealed a large endocervical polyp (12 x 13 x 30 mm), and a polypectomy was performed. Microscopically, the polyp was covered by a layer of columnar epithelium. It consisted of the following 4 elements: fibrous tissue with chronic inflammation, young cartilage with chondroblastlike cells, young ossification with focal osteoblastlike and osteoclastlike cells, and collagenous tissue. These elements were intimately admixed and there was a gradual transition among these elements. No epithelial elements were recognized. No atypia or mitotic figures were noted. Immunohistochemically, the tumor cells were positive for vimentin, bone morphogenetic protein-2 and transforming growth factor-beta1, and negative for cytokeratins, epithelial membrane antigen, alpha-smooth muscle antigen, CD34, desmin, S100 protein, neuron-specific enolase, p53 protein, and CD45. Macrophages including the giant cells were positive for CD68. Ki-67 labeling was 0.5%. The pathologic diagnosis was endocervical polyp with cartilaginous and osseous metaplasia.


Update on linezolid: the first oxazolidinone antibiotic.
Linezolid is the first of an entirely new class of antibiotics, the oxazolidinones, in decades. It has a spectrum of activity against virtually all important Gram-positive pathogens. The unique mechanism of action of linezolid makes cross-resistance with other antimicrobial agents unlikely. Linezolid has both intravenous and oral formulations and the latter is 100% bioavailable. Since its first approval and marketing in March 2000 in the US, linezolid has gained approval for use in many other countries for the treatment of community-acquired and nosocomial pneumonia, complicated and uncomplicated skin and soft-tissue infections, and infections caused by methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, including cases with concurrent bacteraemia. Several earlier comprehensive reviews summarised the chemistry, mechanism of action, pharmacokinetics, clinical efficacy and safety profile of linezolid. The present review provides an update on the latest data regarding the antimicrobial activity of linezolid versus other commonly used agents, the clinical and health-economic outcomes of linezolid versus vancomycin and teicoplanin, and safety issues.


Molecular mechanisms underlying physical exercise-induced brain BDNF overproduction.
Accumulating evidence supports that physical exercise (EX) is the most effective non-pharmacological strategy to improve brain health. EX prevents cognitive decline associated with age and decreases the risk of developing neurodegenerative diseases and psychiatric disorders. These positive effects of EX can be attributed to an increase in neurogenesis and neuroplastic processes, leading to learning and memory improvement. At the molecular level, there is a solid consensus to involve the neurotrophin brain-derived neurotrophic factor (BDNF) as the crucial molecule for positive EX effects on the brain. However, even though EX incontestably leads to beneficial processes through BDNF expression, cellular sources and molecular mechanisms underlying EX-induced cerebral BDNF overproduction are still being elucidated. In this context, the present review offers a summary of the different molecular mechanisms involved in brain's response to EX, with a specific focus on BDNF. It aims to provide a cohesive overview of the three main mechanisms leading to EX-induced brain BDNF production: the neuronal-dependent overexpression, the elevation of cerebral blood flow (hemodynamic hypothesis), and the exerkine signaling emanating from peripheral tissues (humoral response). By shedding light on these intricate pathways, this review seeks to contribute to the ongoing elucidation of the relationship between EX and cerebral BDNF expression, offering valuable insights into the potential therapeutic implications for brain health enhancement.


E2F3 transcription factor: A promising biomarker in lung cancer.
Many researches aiming to explore the pathogenesis of lung cancer have extensively studied the molecular alteration in such disease. In the present study we measured the blood E2F3 mRNA using real-time RT-PCR technique in order to evaluate its clinical significance in early diagnosis and monitoring of lung cancer. This case-control study included 50 lung cancer patients, 20 patients with benign lung diseases and 20 healthy controls. Relative quantification of blood E2F3 mRNA was done by real-time RT-PCR. Blood E2F3 mRNA levels were significantly higher in lung cancer patients when compared to either patients with benign lung diseases or healthy subjects. This elevation was significant in those with metastatic lung cancer as compared to those with localized lung cancer. At a cutoff^{(2-Δ Δ CT)} 1.5, blood E2F3 mRNA was able to distinguish malignant from benign lung conditions with a diagnostic sensitivity of 100%; while at a cutoff^{(2-Δ Δ CT)} 5.3, blood E2F3 mRNA discriminated localized from metastatic lung cancer with a sensitivity of 93.6%. Blood E2F3 mRNA is a sensitive diagnostic marker in lung cancer; moreover, it is a promising prognostic marker capable of efficiently discriminating early from late stages of the disease.


Patterns and contrasts in ophthalmic investigation.
The Snellen test has been the most popular clinical measurement of spatial vision for over a century, but it does not fully express the visual ability of an individual. For more analytical purposes the information capacity of the visual system may be assessed by tests of contrast sensitivity and peripheral vision. The visual system selectively reduces the spatial information content of the visual field to avoid overloading the limited capacity for perception and decision making in the brain. The ways in which this reduction occurs and the processing of spatial information is of interest in many disciplines, and theoretical knowledge has been accelerated by the study of artificial intelligence. These processes may be investigated in human subjects by psychophysical and electrophysiological techniques. This provides additional information for diagnostic purposes and will form the basis of new systems of clinical investigation.


[Lithium while breastfeeding: Case report].
Lithium therapy is currently a cornerstone of treatment for mothers who suffer bipolar disorders. Those who wish to breastfeed their children are often told they have to decide whether modifying the treatment for their disorder or even avoiding lactation. Lithium administration during breastfeeding has been described to produce certain side effects such as thyroid disorders, hypothermia and hypotonia. To our knowledge, there are few publications where infants have no laboratory abnormalities. Here we present the case of an infant without renal or thyroid alteration while he was breastfed.


Differential relations of executive functioning to borderline personality disorder presentations in adolescents.
Borderline personality disorder (BPD) in adolescents is highly complex and heterogeneous. Within the disorder, research has suggested the existence of at least two subgroups: one with predominantly internalizing psychopathology features and one with predominantly externalizing psychopathology features. One process that may differentiate these groups is executive functioning (EF), given that poor EF is linked to externalizing psychopathology. Against this background, the current study used a multi-informant approach to examine whether adolescent patients with predominantly externalizing BPD presentations experience greater deficits in EF than adolescent patients with predominantly internalizing presentations. The sample included inpatient adolescents ages 12-17 (M = 15.26; SD = 1.51). Analyses revealed that multiple EF domains distinguished the BPD subgroups. More specifically, adolescents with externalizing presentations exhibited greater difficulties in broad domains related to global executive functioning, metacognition and behavioural regulation and specific domains related to inhibitory control, working memory, planning/organizing, monitoring and organization of materials. While this study is the first to examine EF and adolescent BPD in the context of internalizing and externalizing psychopathology, alternative approaches to examining this question are discussed. Copyright © 2018 John Wiley & Sons, Ltd.


Evaluation of a nanoemulsion formulation strategy for oral bioavailability enhancement of danazol in rats and dogs.
The objective of this study was to determine whether nanoemulsion formulations constitute a viable strategy to improve the oral bioavailability of danazol, a compound whose poor aqueous solubility limits its oral bioavailability. Danazol-containing oil-in-water nanoemulsions (NE) with and without cosurfactants stearylamine (SA) and deoxycholic acid (DCA) were prepared and characterized. Nanoemulsion droplets size ranging from 238 to 344 nm and with surface charges of -24.8 mV (NE), -26.5 mV (NE-DCA), and +27.8 mV (NE-SA) were reproducibly obtained. Oral bioavailability of danazol in nanoemulsions was compared with other vehicles such as PEG400, 1% methylcellulose (MC) in water (1% MC), Labrafil, and a Labrafil/Tween 80 (9:1) mixture, after intragastric administration to rats and after oral administration of NE-SA, a Labrafil solution, or a Danocrine® tablet to dogs. The absolute bioavailability of danazol was 0.6% (PEG400), 1.2% (1% MC), 6.0% (Labrafil), 7.5% (Labrafil/Tween80), 8.1% (NE-DCA), 14.8% (NE), and 17.4% (NE-SA) in rats, and 0.24% (Danocrine), 6.2% (Labrafil), and 58.7% (NE-SA) in dogs. Overall, danazol bioavailability in any nanoemulsion was higher than any other formulation. Danazol bioavailability from NE and NE-SA was 1.8- to 2.2-fold higher than NE-DCA nanoemulsion and could be due to significant difference in droplet size.


Type III Hyperlipoproteinemia: Still Worth Considering?
Familial type III hyperlipoproteinemia (HLP) was first recognized as a distinct entity over 60 years ago. Since then, it has proven to be instructive in identifying the key role of apolipoprotein E (apoE) in removal of the remnants of very low density lipoproteins and chylomicrons produced by the action of lipoprotein lipase on these triglyceride-transporting lipoproteins. It has additionally shed light on the potent atherogenicity of the remnant lipoproteins. This review describes the history of development of our understanding of type III HLP, discusses the several genetic variants of apoE that play roles in the genesis of type III HLP, and describes the remarkable responsiveness of this fascinating disorder to lifestyle modification, especially carbohydrate restriction and calorie restriction, and, when required, the addition of pharmacotherapy.


External validation of the Scandinavian guidelines for management of minimal, mild and moderate head injuries in children.
Clinical decision rules (CDRs) aid in the management of children with traumatic brain injury (TBI). Recently, the Scandinavian Neurotrauma Committee (SNC) has published practical, evidence-based guidelines for children with Glasgow Coma Scale (GCS) scores of 9-15. This study aims to validate these guidelines and to compare them with other CDRs. A large prospective cohort of children (< 18 years) with TBI of all severities, from ten Australian and New Zealand hospitals, was used to assess the SNC guidelines. Firstly, a validation study was performed according to the inclusion and exclusion criteria of the SNC guideline. Secondly, we compared the accuracy of SNC, CATCH, CHALICE and PECARN CDRs in patients with GCS 13-15 only. Diagnostic accuracy was calculated for outcome measures of need for neurosurgery, clinically important TBI (ciTBI) and brain injury on CT. The SNC guideline could be applied to 19,007/20,137 of patients (94.4%) in the validation process. The frequency of ciTBI decreased significantly with stratification by decreasing risk according to the SNC guideline. Sensitivities for the detection of neurosurgery, ciTBI and brain injury on CT were 100.0% (95% CI 89.1-100.0; 32/32), 97.8% (94.5-99.4; 179/183) and 95% (95% CI 91.6-97.2; 262/276), respectively, with a CT/admission rate of 42% (mandatory CT rate of 5%, 18% CT or admission and 19% only admission). Four patients with ciTBI were missed; none needed specific intervention. In the homogenous comparison cohort of 18,913 children, the SNC guideline performed similar to the PECARN CDR, when compared with the other CDRs. The SNC guideline showed a high accuracy in a large external validation cohort and compares well with published CDRs for the management of paediatric TBI.


Xylarodons A and B, new hexaketides from the endophytic fungus Xylaria sp. SC1440.
Two new hexaketides, xylarodons B (1) and C (2), were isolated from solid cultures of the endophytic fungus Xylaria sp. SC1440. The structures of these compounds were elucidated on the basis of detailed 1D, 2D NMR, and HRESIMS analysis. Their absolute configurations were established by experimental and TDDFT calculated ECD spectra. The isolated compounds were evaluated for cytotoxic and tyrosinase inhibitory activity.


Potential of targeting natural killer T cells for the treatment of autoimmune diseases.
Abstract Natural killer (NK) T cells emerge as unique lymphocytes subsets implicated in the regulation of autoimmunity. Abnormalities in the numbers and functions of NKT cells have been observed in patients with diverse autoimmune diseases as well as in a variety of mouse strains that are genetically predisposed for the development of autoimmune diseases. Unlike conventional T cells that recognize peptides in association with major histocompatibility complex (MHC), NKT cells recognize glycolipid antigens presented by the nonpolymorphic MHC class I-like protein, CD1d. Recently, vigorous activation of NKT cells by synthetic glycolipids such as α-galactosylceramide (α-GC) or its sphingosine truncated derivative OCH have been shown to suppress autoimmune diseases such as experimental auto-immune encephalomyelitis (EAE), diabetes in nonobese diabetic (NOD) mice, and collagen-induced arthritis (CIA) by inducing T helper (Th) 2 bias of autoimmune T cells. In this review, we examine the potential roles of NKT cells in the pathogenesis of autoimmune disease regulation, and the recent advances in glycolipid therapy for autoimmune disease models. In addition, we summarize studies suggesting a role for NKT cells in human autoimmune disease, and discuss the potential of targeting NKT cells for the treatment of autoimmunity.


Inhibitory effect of thiopental on ultra-rapid delayed rectifier K+ current in H9c2 cells.
Using the whole-cell voltage clamp technique, we investigated the effects of thiopental on membrane currents in H9c2 cells, a cell line derived from embryonic rat heart. Thiopental blocked a rapidly activating, very slowly-inactivating ultra-rapid type I(Kur)-like outward K(+) current in a concentration-dependent manner. The half-maximal concentration (IC(50)) of thiopental was 97 microM with a Hill coefficient of 1.2. The thiopental-sensitive current was also blocked by high concentrations of nifedipine (IC(50) = 9.1 microM) and 100 microM chromanol 293B, a blocker of slowly activating delayed rectifier K+ current (I(Ks)), but was insensitive to E-4031, an inhibitor of rapidly activating delayed rectifier K(+) current (I(Kr)). TEA (tetraethylammonium) at 5 mM and 4-AP (4-aminopiridine) at 1 mM reduced the K(+) current to 30.8 +/- 12.2% and 20.5 +/- 6.5% of the control, respectively. Using RT-PCR, we detected mRNAs of Kv2.1, Kv3.4, Kv4.1, and Kv4.3 in H9c2 cells. Among those, Kv2.1 and Kv3.4 have I(Kur)-type kinetics and are therefore candidates for thiopental-sensitive K(+) channels in H9c2 cells. This is the first report showing that thiopental inhibits I(Kur). This effect of thiopental may be involved in its reported prolongation of cardiac action potentials.


An Enlarged and Infected Prostatic Utricle as a Rare Cause of Lower Urinary Tract Symptoms in Adolescent Males.
Dysuria with lower abdominal pain is a common presentation for a urinary tract infection (UTI), and diagnosis is based on symptoms together with a urinalysis and urine culture suggestive of infection. UTI is uncommon in circumcised males who are not sexually active. When urine culture is negative, alternate diagnoses including, but not limited to, gastroenteritis, severe constipation, appendicitis, or epididymitis need to be considered. In patients with a known urologic history of proximal hypospadias and/or disorders of sexual development, rarer diagnoses also need to be considered. This paper reports the case of a 13-year-old male with a remote history of proximal hypospadias repair, who presented with nonspecific lower urinary tract symptoms. Initially he was treated for UTI. However, urine cultures remained negative despite persistent urinary tract symptoms. On further workup, he was found to have an enlarged and infected prostatic utricle. This report illustrates the importance of considering an enlarged prostatic utricle in the differential diagnoses of patients with chronic lower urinary tract symptoms and a history of hypospadias. Additionally, this case highlights the utility of magnetic resonance imaging (MRI) in clarifying lower urinary tract anatomy in cases where ultrasound is inconclusive.


[Immunohistochemical demonstration of the proliferation zone of the gastric mucosa].
The area of proliferation in the mucosa of the gastric antrum and fundus was demonstrated immunohistochemically in an unselected sample of biopsy material using the monoclonal antibody Ki 67. The findings in normal noninflamed preparations were compared with preparations of chronic superficial gastritis and a small group of advanced, partially atrophic gastritis. In all preparations the site of the proliferation was typically in the neck of the gastric glands and in the lower area of the gastric pits. However, in the fundus these areas were much narrower than in the antrum. Only isolated positively labelled cells were found outside the proliferation zone in the specific gland body and in the upper part of the gastric pits near the surface of the mucosa. There was a distinct increase of the breadth of the proliferation zone and the labelling index in chronic inflammatory processes. However, pronounced spreading or displacement of the proliferative cell population to the surface was not shown. In all preparations the areas of proliferation contained both positively labelled cells within the cell cycle and varying numbers of nonlabelled nuclei, which may be considered to be a resting reserve population.


Eye-tracking in surgery: a systematic review.
Surgery is constantly evolving with the assistance of rapidly developing novel technology. Eye-tracking devices provide opportunities to monitor the acquisition of surgical skills, gain insight into performance, and enhance surgical practice. The aim of this review was to consolidate the available evidence for the use of eye-tracking in the surgical disciplines. A systematic literature review was conducted in accordance with PRISMA guidelines. A search of OVID Medline, EMBASE, Cochrane library, Scopus, and Science Direct was conducted January 2000 until December 2022. Studies involving eye-tracking in surgical training, assessment and technical innovation were included in the review. Non-surgical procedures, animal studies, and studies not involving surgical participants were excluded from the review. The search returned a total of 12 054 articles, 80 of which were included in the final analysis and review. Seventeen studies involved eye-tracking in surgical training, 48 surgical assessment, and 20 were focussing on technical aspects of this technology. Twenty-six different eye-tracking devices were used in the included studies. Metrics such as the number of fixations, duration of fixations, dwell time, and cognitive workload were able to differentiate between novice and expert performance. Eight studies demonstrated the effectiveness of gaze-training for improving surgical skill. The current literature shows a broad range of utility for a variety of eye-tracking devices in surgery. There remains a lack of standardization for metric parameters and gaze analysis techniques. Further research is required to validate its use to establish reliability and create uniform practices.


Detection of spacer precursors formed in vivo during primed CRISPR adaptation.
Type I CRISPR-Cas loci provide prokaryotes with a nucleic-acid-based adaptive immunity against foreign DNA. Immunity involves adaptation, the integration of ~30-bp DNA fragments, termed prespacers, into the CRISPR array as spacers, and interference, the targeted degradation of DNA containing a protospacer. Interference-driven DNA degradation can be coupled with primed adaptation, in which spacers are acquired from DNA surrounding the targeted protospacer. Here we develop a method for strand-specific, high-throughput sequencing of DNA fragments, FragSeq, and apply this method to identify DNA fragments accumulated in Escherichia coli cells undergoing robust primed adaptation by a type I-E or type I-F CRISPR-Cas system. The detected fragments have sequences matching spacers acquired during primed adaptation and function as spacer precursors when introduced exogenously into cells by transformation. The identified prespacers contain a characteristic asymmetrical structure that we propose is a key determinant of integration into the CRISPR array in an orientation that confers immunity.


A phylogenetically conserved sequence within viral 3' untranslated RNA pseudoknots regulates translation.
Both the 68-base 5' leader (omega) and the 205-base 3' untranslated region (UTR) of tobacco mosaic virus (TMV) promote efficient translation. A 35-base region within omega is necessary and sufficient for the regulation. Within the 3' UTR, a 52-base region, composed of two RNA pseudoknots, is required for regulation. These pseudoknots are phylogenetically conserved among seven viruses from two different viral groups and one satellite virus. The pseudoknots contained significant conservation at the secondary and tertiary levels and at several positions at the primary sequence level. Mutational analysis of the sequences determined that the primary sequence in several conserved positions, particularly within the third pseudoknot, was essential for function. The higher-order structure of the pseudoknots was also required. Both the leader and the pseudoknot region were specifically recognized by, and competed for, the same proteins in extracts made from carrot cell suspension cells and wheat germ. Binding of the proteins is much stronger to omega than the pseudoknot region. Synergism was observed between the TMV 3' UTR and the cap and to a lesser extent between omega and the 3' UTR. The functional synergism and the protein binding data suggest that the cap, TMV 5' leader, and 3' UTR interact to establish an efficient level of translation.


Protrusion on the Depressed Surface of Non-polypoid T1 Colorectal Cancer Is Associated with Venous Invasion.
The treatment strategies for T1 colorectal cancer (CRC) include both surgical and endoscopic resection. Surgical resection is indicated if lymphovascular invasion is present; however, the endoscopic prediction of lymphovascular invasion has not been reported. We aimed to correlate endoscopic morphology with pathological findings, including lymphovascular invasion, in non-polypoid T1 CRC. We retrospectively investigated 63 patients with non-polypoid T1 CRC surgically resected between 2008 and 2016. Four typical endoscopic findings related to deep submucosal invasion, namely protrusion from a depressed surface, fold convergence, fullness and hardness, were assessed to elucidate their association with pathological findings. Protrusion was the only finding significantly correlated with positive venous invasion (67.9% of the lesions with protrusion vs. 34.3% of those without protrusion, p=0.01), which was also confirmed by a multivariable analysis (odds ratio(OR)=3.72, 95% confidence interval(CI)=1.24-11.2, p=0.02). The endoscopic finding of protrusion on a depressed surface may be a sign indicating venous invasion in non-polypoid T1 CRC.


Inadequate record keeping by dental practitioners.
When a dental practitioner is brought before a disciplinary body, a common finding is that dental records were poorly kept and inadequate to establish issues of consent for treatment or the nature of the treatment undertaken. Often this finding may be incidental to the actual issue that brought the practitioner before a regulatory body or the Courts. The aim of this study was to examine recent cases reported in the State of Victoria involving dental practitioners, specifically seeking those cases where the record keeping was found to be inadequate as an incidental finding. Published rulings of formal complaints and notification cases brought before disciplinary hearings in the State of Victoria for the period January 2000 to June 2014 were analysed with regards to orders made in respect to record keeping. Complaints and notifications specific to dental record keeping accounted for less than 2% of formal complaints. And yet up to 75% of cases have made a finding of unprofessional conduct against a dental practitioner on the basis of inadequate record keeping, most often in combination with other breaches of conduct. Adherence to the traditional format of handwriting or typing entries into patient records may contribute to the problem of poor record keeping in a clinical dental setting. Newer technologies such as digital intraoral and extraoral photography and audio-recording of patient interactions may offer a solution to the problems of record keeping.


High-resolution mass-selective UV spectroscopy of pseudoephedrine: evidence for conformer-specific fragmentation.
Using resonance-enhanced two-photon ionization spectroscopy with mass resolution of jet-cooled molecules, a low-resolution S(1) ← S(0) vibronic spectrum of pseudoephedrine was recorded at the mass channels of three distinct fragments with m/z = 58, 71, and 85. Two of the fragments, with m/z = 71 and 85, are observed for the first time for this molecule. The vibronic spectra recorded at different mass channels feature different patterns, implying that they originate from different conformers in the cold molecular beam, following conformer-specific fragmentation pathways. Highly resolved spectra of all prominent vibronic features were measured, and from their analysis based on genetic algorithms, the molecular parameters of the conformers giving rise to the respective bands have been determined. Comparing the experimental results with those obtained from high-level ab initio quantum chemistry calculations, the observed prominent vibronic bands have been assigned to originate from four distinct conformers. The conformers are separated into two groups that have different fragmentation pathways determined by the different intramolecular interactions.


Macrolides induce severe cardiotoxicity and developmental toxicity in zebrafish embryos.
Macrolide antibiotics (MALs) are widely used for both human and animal health. Most MALs and their metabolites transfer into aquatic organisms and environment resulting in violent consequences. Previous studies show that MALs cause cardiotoxicity in humans and mammals. However, the potential risk of these chemicals in aquatic organisms remains unclear. Here, we used zebrafish embryos as a model to evaluate the toxicity of MALs. Zebrafish embryos were exposed to four typical MALs including azithromycin (AZM), clarithromycin (CLR), tilmicosin (TMS) and tylosin (TYL) to study their cardiotoxicity. The heart rate of zebrafish embryos showed similar biphasic distribution in the presence of four MALs at 2 days post-fertilization (dpf). The heart rate increased significantly at low levels of MALs while decreased obviously at high levels. Subsequently, TMS was chose to study its acute toxicity and developmental toxicity, which caused pericardial edema and spinal curvature in zebrafish embryos at 4 dpf. Furthermore, we found that TMS triggered oxidative stress, with decreased SOD activities and increased MDA contents. Lastly, apoptosis was observed in zebrafish embryos under TMS treatment, with up-regulation of apoptosis associated genes such as p53, bcl 2, bax, caspase 3 and caspase 9, confirmed by increased protein expression based on Western blot analysis. Taken together, these data indicate that MALs can cause serious toxicity in the development of zebrafish. Great caution should be taken due to the huge consumption of MALs for food animal production and treatments with TMS for infections in aquaculture.


One-step synthesis of imidazoles from Asmic (anisylsulfanylmethyl isocyanide).
Substituted imidazoles are readily prepared by condensing the versatile isocyanide Asmic, anisylsulfanylmethylisocyanide, with nitrogenous π-electrophiles. Deprotonating Asmic with lithium hexamethyldisilazide effectively generates a potent nucleophile that efficiently intercepts nitrile and imine electrophiles to afford imidazoles. In situ cyclization to the imidazole is promoted by the conjugate acid, hexamethyldisilazane, which facilitates the requisite series of proton transfers. The rapid formation of imidazoles and the interchange of the anisylsulfanyl for hydrogen with Raney nickel make the method a valuable route to mono- and disubstituted imidazoles.


Disease mapping of early- and late-stage cancer to monitor inequalities in early detection: a study of cutaneous malignant melanoma.
We consider disease mapping of early- and late-stage cancer, in order to identify and monitor inequalities in early detection. Our method is demonstrated by mapping cancer incidence at high geographical resolution using data on 10,302 cutaneous malignant melanoma (CMM) cases within the 3.7 million population of South-West Sweden. The cases were geocoded into small-areas, each with a population size between 600 and 2600 and accessible socio-demographic data. Using the disease mapping application Rapid Inquiry Facility (RIF) 4.0, we produced regional maps to visualise spatial variations in stage I, II and III-IV CMM incidences, complemented by local maps to explore the variations within two urban areas. Pronounced spatial disparities in stage I CMM incidence were revealed by the regional and local maps. Stage I CMM incidence was markedly higher in wealthier small-areas, in particular within each urban area. A twofold higher stage I incidence was observed, on average, in the wealthiest small-areas (upper quintile) than in the poorest small-areas (lower quintile). We identified in the regional map of stage III-IV CMM two clusters of higher or lower than expected late-stage incidences which were quite distinct from those identified for stage I. In conclusion, our analysis of CMM incidences supported the use of this method of cancer stage incidence mapping for revealing geographical and socio-demographic disparities in cancer detection.


A zebrafish in vivo phenotypic assay to identify 3-aminothiophene-2-carboxylic acid-based angiogenesis inhibitors.
Abstract Small molecules that inhibit angiogenesis are attractive drug candidates for cancer, retinopathies, and age-related macular degeneration. In vivo, phenotypic screening in zebrafish (Danio rerio) emerges as a powerful methodology to identify and optimize novel compounds with pharmacological activity. Zebrafish provides several advantages for in vivo phenotypic screens especially for angiogenesis, since it develops rapidly, externally, and does not rely on a functional cardiovascular system to survive for several days during development. In this study, we utilize a transgenic line that allows the noninvasive monitoring of angiogenesis at a cellular level. The inhibition of angiogenesis can be observed under a fluorescent stereoscope and quantified. To exemplify the versatility and robustness of the zebrafish screen, we have employed a series of 60 novel compounds that were designed based on a potent VEGFR2 inhibitor. Herein, we report their structure-based design, synthesis, and in vivo zebrafish screening for optimal activity, toxicity, and off-target effects, which revealed six reversible inhibitors of angiogenesis.


Controlled release of dexamethasone from PLGA microspheres embedded within polyacid-containing PVA hydrogels.
The development of zero-order release systems capable of delivering drug(s) over extended periods of time is deemed necessary for a variety of biomedical applications. We hereby describe a simple, yet versatile, delivery platform based on physically cross-linked poly(vinyl alcohol) (PVA) microgels (cross-linked via repetitive freeze/thaw cycling) containing entrapped dexamethasone-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres for controlled delivery over a 1-month period. The incorporation of polyacids, such as humic acids, Nafion, and poly(acrylic acid), was found to be crucial for attaining approximately zero-order release kinetics, releasing 60% to 75% of dexamethasone within 1 month. Microspheres alone entrapped in the PVA hydrogel resulted in negligible drug release during the 1-month period of investigation. On the basis of a comprehensive evaluation of the structure-property relationships of these hydrogel/microsphere composites, in conjunction with their in vitro release performance, it was concluded that these polyacids segregate on the PLGA microsphere surfaces and thereby result in localized acidity. These surface-associated polyacids appear to cause acid-assisted hydrolysis to occur from the surface inwards. Such systems show potential for a variety of localized controlled drug delivery applications such as coatings for implantable devices.


Problems of accuracy in official statistics on drug-related deaths.
The accuracy of statistics on drug-related deaths depends on numerous processes at work from the investigation of the death-scene to the categorization of the case in official statistics. This article discusses problems in lack of information, pressures on medical examiners, definition, nomenclature, and conventions of coding. The implications for comparisons of rates of drug-related deaths across ethnic groups and geographic areas are discussed.


Plasma folate levels and associated factors in women planning to become pregnant in a population with high prevalence of neural tube defects.
Optimal blood folate levels of women before pregnancy are critical to the prevention of neural tube defects (NTDs). However, few studies have focused on blood folate levels of women planning to become pregnant. The aims of this study were to assess plasma folate levels in women who planned to become pregnant in a population with high prevalence of NTDs, to identify factors associated with plasma folate levels, and to evaluate the risk of NTDs at the population level. A total of 2065 women were enrolled at the time of premarital health check-up in two rural counties in northern China from November 2009 to December 2012. Fasting venous blood samples were collected and plasma folate concentrations were measured by microbiological method. The overall median of plasma folate was 10.5 nmol/L. 50% of the women had a plasma folate level below 10.5 nmol/L, a cutoff for megaloblastic anemia, and 88% below 18 nmol/L, a proposed optimal plasma folate level for the prevention of NTDs. Folic acid supplementation was the only factor to be associated with plasma folate concentrations, but only 1.9% of the women reported having taken folic acid supplements. A population risk of 29.3 NTD cases per 10,000 births was predicted. Women who planned to become pregnant had very low plasma folate in the population. Folic acid supplementation was the only factor to be associated with a high plasma folate concentration. High NTD risk would remain if women would get pregnant without having taken folic acid supplements. Birth Defects Research 109:1039-1047, 2017. © 2017 Wiley Periodicals, Inc.


Clinical, biochemical, and genetic aspects of Sjögren-Larsson syndrome.
Sjögren-Larsson syndrome (SLS) is caused by an autosomal recessive mutation in ALDH3A2, which encodes the fatty aldehyde dehydrogenase responsible for the metabolism of long-chain aliphatic aldehydes and alcohols. The pathophysiologic accumulation of aldehydes in various organs, including the skin, brain, and eyes, leads to characteristic features of ichthyosis, intellectual disability, spastic di-/quadriplegia, and low visual acuity with photophobia. The severity of the clinical manifestations thereof can vary greatly, although most patients are bound to a wheelchair due to contractures. To date, correlations between genotype and phenotype have proven difficult to document due to low disease incidence and high heterogenetic variability in mutations. This review summarizes the clinical characteristics of SLS that have been found to contribute to the prognosis thereof, as well as recent updates from genetic and brain imaging studies. In addition, the differential diagnoses of SLS are briefly illustrated, covering cerebral palsy and other genetic or neurocutaneous syndromes mimicking the syndrome.


The complete mitochondrial genome of Cupido argiades (Lepidoptera: Lycaenidae).
The complete mitogenome of Cupido argiades (Lepidoptera: Lycaenidae) was determined in this study. The genome is 15,330 bp long, presenting a typical gene organization and order for completely sequenced lepidopoteran mitogenomes. All protein-coding genes (PCGs) are initiated by ATN codons, except for cox1, which uses CGA as its start codon. Some PCGs harbor TAG (nad3) or incomplete termination codon T (cox1, cox2, nad5), while others use standard canonical TAA as their termination codons. Furthermore, the largest noncoding A+T-rich region with the length of 450 bp contains two microsatellite-like repeats of (TA)9 and a conserved motif ATAGA followed by a 19-bp poly-T stretch.


[J.M. Charcot's library at the Salpêtrière Hospital in Paris].
In 1906, the personal scientific books collection of J.M. Charcot (1825-1893) was bequeathed by his son, the explorer J.B. Charcot, to the Neurological Disease Unit-Salpêtrière Hospital in Paris. This library died progressively. In the same time, so did the Anatomical Museum, founded to by J.M. Charcot, and also settled in the "Division Pariset". Since 1966, with help of the late Professeur P. Castaigne, and collaborators, the library is reviving. It increased with several gifts of personal libraries, from Dr. Souques, Pr. Mollaret, Pr. Alajouanine, Pr. Lhermitte, Pr. Signoret. It is now the "Bibliothèque de Neurosciences J.M. Charcot-Paris VI University".


Antidepressant-induced sexual dysfunction.
This article reviews current evidence regarding sexual side effects of antidepressant drugs. Controlled studies have demonstrated that some antidepressant drugs have adverse effects on orgasm and libido. Orgasmic dysfunction and ejaculatory delay appear to be common sexual side effects of the serotonin selective reuptake inhibitors (SSRIs). A variety of treatment options are available if a patient experiences antidepressant-induced sexual dysfunction. Often, modification of the pharmacologic regimen will restore sexual function while maintaining antidepressant activity. The frequency of sexual side effects reported with the SSRIs mandates that the clinician inquire about sexual function if these agents are used. Bupropion and nefazodone appear to have an unusually low incidence of sexual side effects.


Glucagon-Like Peptide-1 Receptor Agonist Protects Against Diabetic Cardiomyopathy by Modulating microRNA-29b-3p/SLMAP.
Our aims were to investigate the pathogenesis of diabetic cardiomyopathy (DCM) and to explore the protective effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) on DCM. After 12 weeks of treatment with exenatide-loaded microspheres, a long-acting GLP-1RA, in DCM mice, cardiac structure and function were evaluated by plasma B-type natriuretic peptide (BNP), echocardiography, H&E, oil red and Sirius staining. The expression of glucagon-like peptide-1 receptor in mouse heart tissue was determined by immunofluorescence staining. The label-free proteomic analysis of cardiac proteins was conducted among control, DCM and DM+GLP-1RA groups. Then, quantitative real-time PCR, Western blotting and dual-luciferase reporter assay were performed to verify the regulation of target protein by the upstream microRNA (miRNA). GLP-1RA treatment obviously improved serum BNP, myocardial fibrosis, lipid deposition of the myocardium and echocardiography parameters in DCM mice. Sarcolemmal membrane-associated protein (SLMAP) was one of 61 differentially expressed cardiac proteins found in three groups by proteomic analysis. Up-regulation of microRNA-29b-3p (miR-29b-3p) and down-regulation of SLMAP were found in the ventricular myocardium of GLP-1RA-treated DCM mice. SLMAP was a target of miR-29b-3p, while GLP-1RA regulated SLMAP expression through miR-29b-3p. Furthermore, inhibition of glucagon-like peptide-1 receptor (GLP-1R) in cardiomyocytes reversed the effects of GLP-1RA on miR-29b/SLMAP. SLMAP may play roles in the pathogenesis of DCM and may be a target of GLP-1RA in protecting against DCM. After binding to myocardial GLP-1R, GLP-1RA can regulate the expression of myocardial SLMAP through miR-29b-3p.


The role of body surface area in quantity discrimination in angelfish (Pterophyllum scalare).
Although some fish species have been shown to be able to discriminate between two groups (shoals) of conspecifics differing in the number of members, most studies have not controlled for continuous variables that covary with number. Previously, using angelfish (Pterophyllum scalare) we started the systematic analysis of the potential influence of such continuous variables, and found that they play different roles in shoal discrimination depending on whether large (≥ 4 fish) or small (<4 fish) shoals were contrasted. Here, we examine the potential role of the overall body surface area of stimulus fish in shoal preference, a prominent variable not yet examined in angelfish. We report that both when numerically large (5 versus 10 fish) and when small (2 versus 3 fish) shoals were contrasted, angelfish were unable to discriminate the numerically different shoals as long as the surface area of the contrasted shoals was equated. Thus, we conclude that body surface may be an important continuous variable in shoal discrimination. This conclusion was further supported by the analysis of preference when shoals of the same numerical size but different body surface area were contrasted. We found subjects to spend significantly more time close to the shoals with the greater overall surface area. Last, we conducted an experiment in which we simultaneously controlled a set of continuous variables, including overall surface area, and found angelfish to use the number of shoal members as a cue only in large shoal contrasts but not in small shoal contrasts. This result suggests the potential existence of different processing systems for large and small numbers in fish.


Poly(2-(dimethylamino)ethyl methacrylate)-modified nanoporous Colloidal films with pH and ion response.
Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes were grown using surface-initiated atom transfer radical polymerization on the nanopore surface inside the colloidal films assembled from 255 nm silica spheres. The molecular transport through PDMAEMA-modified colloidal nanopores was studied as a function of pH and ionic strength by measuring the flux of neutral and positively charged redox-active species across the colloidal films using cyclic voltammetry. Nanopores modified with PDMAEMA brushes exhibited pH- and ion-dependent behavior as follows. The diffusion rates decreased with decreasing pH as a result of electrostatic interactions and steric hindrance. At low pH (in the protonated state) the diffusion rates increased with increasing salt concentration because of the charge screening. We also quaternized the surface-grafted PDMAEMA, which led to the formation of strong polyelectrolyte brushes that hindered the diffusion of neutral molecules through the nanopores due to steric effects and the diffusion of positively charged species due to both electrostatic and steric effects.


All four Sendai Virus C proteins bind Stat1, but only the larger forms also induce its mono-ubiquitination and degradation.
Sendai virus infection strongly induces interferon (IFN) production and has recently been shown to interdict the subsequent IFN signaling through the Jak/Stat pathway. This anti-IFN activity of SeV is due to its "C" proteins, a nested set of four proteins (C', C, Y1, Y2) that carry out a nested set of functions in countering the innate immune response. We previously reported that all four C proteins interact with Stat1 to prevent IFN signaling through the Jak/Stat pathway. Nevertheless, only the longer C proteins reduced Stat1 levels and prevented IFN from inducing an antiviral (VSV) state, or apoptosis, in IFN-competent murine cells. Here, we investigate the mechanism by which the various C proteins differentially affect the host antiviral defenses. All four C proteins were found to physically associate with Stat1 during cell culture infections, and in vitro in the absence of other viral gene products (as evidenced by co-immunoprecipitation). In addition, the inability of a null mutant (C(F170S)) to bind Stat1 suggests that this interaction is physiologically relevant. We have also shown that the proteasomal inhibitor MG132 can prevent the C protein-induced dismantling of the antiviral (VSV) state in murine cells; thus, the turnover of Stat1 correlates with the C protein-mediated counteraction of the antiviral (VSV) state. The C protein-induced instability of Stat1 was accompanied by a clear increase in the level of mono-ubiquinated Stat1, an unexpected hallmark of protein degradation. Finally, we show that a rSeV with mutant C proteins but wild-type Y proteins (CDelta10-15, that does not counteract the endogenous antiviral (VSV) state of MEFs even though their C proteins bind Stat1 and prevent its activity) is also unable to decrease bulk Stat1 levels or to increase the level of ubiquinated Stat1.


Functionalized polypyrrole film: synthesis, characterization, and potential applications in chemical and biological sensors.
In this paper, we report the synthesis of a carboxyl-functionalized polypyrrole derivative, a poly(pyrrole-N-propanoic acid) (PPPA) film, by electrochemical polymerization, and the investigation of its basic properties via traditional characterization techniques such as confocal-Raman, FTIR, SEM, AFM, UV-vis, fluorescence microscopy, and contact-angle measurements. The experimental data show that the as-prepared PPPA film exhibits a hydrophilic nanoporous structure, abundant -COOH functional groups in the polymer backbone, and high fluorescent emission under laser excitation. On the basis of these unique properties, further experiments were conducted to demonstrate three potential applications of the PPPA film in chemical and biological sensors: a permeable and permselective membrane, a membrane with specific recognition sites for biomolecule immobilization, and a fluorescent conjugated polymer for amplification of fluorescence quenching. Specifically, the permeability and permselectivity of ion species through the PPPA film are detected by means of rotating-disk-electrode voltammetry; the specific recognition sites on the film surface are confirmed with protein immobilization, and the amplification of fluorescence quenching is measured by the addition of a quenching agent with fluorescence microscopy. The results are in good agreement with our expectations.


Global and non-Global slow oscillations differentiate in their depth profiles.
Sleep slow oscillations (SOs, 0.5-1.5 Hz) are thought to organize activity across cortical and subcortical structures, leading to selective synaptic changes that mediate consolidation of recent memories. Currently, the specific mechanism that allows for this selectively coherent activation across brain regions is not understood. Our previous research has shown that SOs can be classified on the scalp as Global, Local or Frontal, where Global SOs are found in most electrodes within a short time delay and gate long-range information flow during NREM sleep. The functional significance of space-time profiles of SOs hinges on testing if these differential SOs scalp profiles are mirrored by differential depth structure of SOs in the brain. In this study, we built an analytical framework to allow for the characterization of SO depth profiles in space-time across cortical and sub-cortical regions. To test if the two SO types could be differentiated in their cortical-subcortical activity, we trained 30 machine learning classification algorithms to distinguish Global and non-Global SOs within each individual, and repeated this analysis for light (Stage 2, S2) and deep (slow wave sleep, SWS) NREM stages separately. Multiple algorithms reached high performance across all participants, in particular algorithms based on k-nearest neighbors classification principles. Univariate feature ranking and selection showed that the most differentiating features for Global vs. non-Global SOs appeared around the trough of the SO, and in regions including cortex, thalamus, caudate nucleus, and brainstem. Results also indicated that differentiation during S2 required an extended network of current from cortical-subcortical regions, including all regions found in SWS and other basal ganglia regions, and amygdala and hippocampus, suggesting a potential functional differentiation in the role of Global SOs in S2 vs. SWS. We interpret our results as supporting the potential functional difference of Global and non-Global SOs in sleep dynamics.


Stimulation of regulatory volume decrease (RVD) by isolated bovine articular chondrocytes following F-actin disruption using latrunculin B.
Articular chondrocytes are exposed to significant changes in extracellular osmolarity during normal joint activity, which can lead to changes in cell volume and metabolism of the extracellular matrix (ECM). Chondrocytes can respond to cell swelling/shrinking by volume regulatory pathways, but the signalling pathways are poorly understood although a role for the cytoskeleton is frequently implicated. Here, we have investigated the effects of disruption of the chondrocyte F-actin cytoskeleton on the recovery of cell volume by RVD. The cytoskeleton was perturbed using the relatively specific agent latrunculin B (5 microM; 30 min) and loss of F-actin integrity quantified using fluorescent phalloidin-labelling and confocal laser scanning microscopy (CLSM). Imaging of isolated chondrocytes labelled with Fura-2 to measure the fluorescence associated with cell volume changes, showed that the extent of hypo-osmotic swelling was unaffected by latrunculin B treatment. Two categories of the chondrocyte RVD response were observed: 'fast' RVD where at 3 min post-osmotic challenge there was a recovery in cell fluorescence of >or=80%, whereas other cells exhibited 'slow' RVD. Latrunculin B increased the proportion of chondrocytes demonstrating 'fast' RVD by approximately 10 fold and reduced those cells showing 'slow' RVD. An inhibitor of chondrocyte RVD (REV 5901) had no significant effect on the integrity of the cytoskeleton showing that the RVD response could be inhibited independent of the state of the F-actin cytoskeleton. These results suggest that the intact cortical F-actin cytoskeleton has a restraining effect on the RVD response of isolated bovine articular chondrocytes.


A Framework for Interpretable Full-Body Kinematic Description Using Geometric and Functional Analysis.
Rapid advances in cost-effective and non-invasive depth sensors, and the development of reliable and real-time 3D skeletal data estimation algorithms, have opened up a new application area in computer vision - statistical analysis of human kinematic data for fast, automated assessment of body movements. These assessments can play important roles in sports, medical diagnosis, physical therapy, elderly monitoring and related applications. This paper develops a comprehensive geometric framework for quantification and statistical evaluation of kinematic features. The key idea is to avoid analysis of individual joints, as is the current paradigm, and represent movements as temporal evolutions, or trajectories, on shape space of full body skeletons. This allows metrics with appropriate invariance properties to be imposed on these trajectories and leads to definitions of higher-level features, such as spatial symmetry (sS), temporal symmetry (tS), action's velocity (Vl) and body's balance (Bl), during performance of an action. These features exploit skeletal symmetries in space and time, and capture motion cadence to naturally quantify motions of individual subjects. The study of these features as functional data allows us to formulate certain hypothesis tests in feature space. This, in turn, leads to validation of existing assumptions and discoveries of new relationships between kinematics and demographic factors, such as age, gender, and athletic training. We use the clinically validated K3Da kinect dataset to illustrate these ideas, and hope these tools will lead to discovery of new relationships between full-body kinematic features and demographic, health, and wellness factors that are clinically relevant.


Cancer-related venous thromboembolism: insight into underestimated risk factors.
Risk factors for cancer-associated VTE include certain cancer types (e.g. pancreatic adenocarcinoma), chemotherapy, and the use of erythropoiesis-stimulating agents, central venous catheters, and surgery. We studied the risk factors for cancer-associated VTE in our institution. Retrospective analysis of patients with solid cancers treated with chemotherapy at King Khalid University Hospital from 2000 to 2010. We assessed risk factors responsible for VTE, including performance status, age, chemotherapy, use of erythropoietin (EPO), stage of disease and use of a central venous catheter. Patients with other co-morbidities such as diabetes were excluded. Forty of 306 patients were identified as having VTE, including 111 males and 195 females with a median age of 38 years (range, 13-18 years). Thirty-nine patients had proximal deep vein thrombosis (DVT) and, 4 had pulmonary embolism with no evidence of DVT. Of the 43 patients, 40 patients had stage III or IV at the time of VTE. Thirty patients were taking erythropoietin (40 000 units/ week); 25 had a hemoglobin level higher than 12 g/L. All patients were treated with low molecular weight (LMW) heparin and maintained on LMW heparin or warfarin for minimum of 6 months. VTE imposes a great risk to life in cancer patients. Risk factors include age more than 40 years, advanced cancer stage, chemotherapy, use of EPO for anemia and underuse of DVT prophylaxis.


Purine and pyrimidine analogues irreversibly prevent passage of lymphocytes from the G1 to the S phase of the cell cycle.
Six-hour pulses of the purine analogue 8-azaguanine (8-AG) and the pyrimidine analogue 5-fluorouracil (5-FU) produced a novel irreversible effect on mouse and human lymphocytes. Cells treated with these analogues early during culture with concanavalin A and then washed in presence of excess natural base could pass normally through the various stages of blast formation (e.g., increased K+ transport, increase in nuclear and cytoplasmic volume, disaggregation of chromatin), but showed a severe inhibition of DNA synthesis when this was measured by [3H]thymidine incorporation at 48 h of culture; this was true irrespective of whether the 6-h pulse with analogue occurred at 0, 12, or 24 h of culture in the presence of mitogen. The analogue 6-mercaptopurine, which strongly inhibited DNA and RNA synthesis while present in the medium, had no irreversible effects, unlike 5-FU and 8-AG. The persistence of the effects of 5-FU in presence of excess thymidine in the medium suggested that inactivation of thymidylate synthetase was not responsible for the inhibition observed here. The effect was expressed in the presence or absence of protein synthesis; therefore, the observed inhibition of proliferation was not due to synthesis of a toxic protein, but to an effect on the formation or function of the DNA synthesizing system and (or) on its template, thus preventing the cells from passing from the G1 to the S phase of the cell cycle.


Effect of sleep deprivation on saccades and eyelid blinking.
In this study the effect of sleep deprivation on specific components of eye and eyelid movement was investigated in a group of young and healthy subjects. The duration of sleep deprivation was 20 h. Each subject had to execute different saccade tasks: reflexive saccades, voluntary prosaccades and antisaccades. Saccade latency, number of saccade errors and blink rate during the saccade tasks were evaluated as predictors of performance decrements resulting from sleep deprivation. The present study showed no significant deterioration of latency and number of errors in the different saccade tasks. However, the blink rate was significantly higher after a night without sleep than before. It is concluded that the blink rate appears to be a promising psychophysical measurement and a more sensitive parameter than saccade performance to evaluate the effects of 20 h of sleep deprivation. These results encourage further research on this topic.


The association between social resources and depression among female migrants affected by domestic violence.
Interpersonal violence (IPV) is associated with higher risk of depression. Female Chinese rural-to-urban migrants may experience greater depression following exposure to IPV due to lack of social support and integration within their receiving communities. The current study estimated the prevalence of IPV among rural-to-urban migrants in Guangzhou, China, and evaluated the moderating effects of social resources on migrant's depression symptoms. We recruited 1,368 women (1,003 migrants and 365 local-born) of childbearing age from population and family planning centers in two districts using a quota sampling method matched to the 2012 population census. Chinese versions of the Conflict Tactics Scale 2 Short Form, Center for Epidemiological Studies Depression Scale and the Social Support Rating Scale measured IPV, depression, and social support. Social integration was measured with a locally derived scale. Migrants reported a similar prevalence for IPV (41.20%) to local women (39.20%). Bivariate comparisons demonstrated that migrants reported greater depression (11.8±8.9 vs. 10.0±8.8, t=-3.27, p<0.001) and less social support (22.2±5.1 vs. 27.1±5.5, t=14.84, p<0.001). Regression analysis indicated that the effect of violence on depression symptoms for migrant women was moderated by social integration. Women who experienced violence and had greater integration in their community reported less depression than women who experienced violence but reported less social integration. A high prevalence of IPV was reported in our sample. Social integration is a key risk factor for migrant mental health. Social services aimed to reduce IPV and integrate migrants in their new communities are needed.


Is esophageal pH monitoring used appropriately in an open-access system? A prospective multicenter study.
To evaluate the referral patterns and indications for esophageal pH monitoring in an open-access system and to determine whether these indications conform to practice guidelines of the American Gastroenterological Association (AGA). A total of 851 consecutive patients referred for ambulatory pH monitoring to nine open-access gastrointestinal units over a 12-month period received a structured interview. The indication for the examination was decided by the physician performing the procedure, on the basis of the patient's clinical history and main complaint. Three hundred and twenty-three (38%) examinations were for indications in accordance with the guidelines. The proportion of appropriate requests in each center ranged from 34% to 47%. This figure was not significantly different in larger gastrointestinal units (more than 150 examinations per year) and smaller ones (35% and 40%; p= 0.14). The proportion of appropriate requests was 45% for gastroenterologists, 38% for surgeons, 32% for other specialists, and 24% for primary care physicians (PCPs) (p < 0.001). The percentage of appropriateness was significantly different between gastrointestinal specialists and PCPs (p < 0.001 vs gastroenterologists, p= 0.015 vs GI surgeons), and between gastroenterologists and other specialists (p= 0.006). The underuse of an empirical trial of acid-suppression therapy in patients with suspected reflux disease and the overuse of this test to confirm a diagnosis in patients with erosive esophagitis and in endoscopy-negative cases with typical symptoms responding completely to antisecretory therapy accounted for most of the referrals, which was not in accordance with the guidelines. In an open-access system, a high proportion of esophageal pH studies are done for indications not consistent with published guidelines, particularly among the examinations not requested by gastrointestinal specialists. Further education is still needed on the appropriate use of esophageal pH monitoring and management of gastroesophageal reflux disease (GERD).


Radiological and pathological correlation of lung malignant tumors treated with percutaneous radiofrequency ablation.
Radiological and histological correlation was evaluated in patients with malignant tumors of the lung that underwent radiofrequency ablation (RFA). One of the patients had a primary lung tumor and another patient had three metastatic lung tumors. RFA was performed under computed tomography (CT) fluoroscopic guidance. CT showed ground glass shadows around the tumoral lesions immediately after RFA, but one week later homogenous opacification without tumoral enhancement was noted. Two months after RFA, most lesions showed cystic changes without activity on FDG-PET. Histological evaluation showed massive coagulation necrosis throughout the tumor and some viable cells at the peripheral areas in all lesions. Although RFA is a promising therapeutic approach for malignant lung tumors, some viable cells may persist in peripheral areas of the tumor.


Mobile ankle and knee perturbator.
A mobile ankle and knee perturbator has been developed. It consists of a functional joint with an integrated clutch. Four Bowden wires connect the joint to a powerful motor and a double pneumatic cylinder. When needed during any time of the gait cycle, it is possible to impose an ankle rotation by engaging the clutch and rotating the ankle or knee joint with a predefined displacement. The system is designed to investigate electrophysiological and biomechanical features of the human ankle or knee joint during gait.


Metabolomics-based study of clinical and animal plasma samples in coronary heart disease with blood stasis syndrome.
The aim of this study is to explore a bridge connecting the mechanism basis and macro syndromes of coronary heart disease with experimental animal models. GC-MS technique was used to detect the metabolites of plasma samples in mini swine models with myocardial infarction (MI) and patients with unstable angina (UA). 30 metabolites were detected in the plasma samples of more than 50 percent of model group and control group in swine, while 37 metabolites were found in the plasma samples of UA patients and healthy control group. 21 metabolites in the plasma samples of swine model and 20 metabolites in patients with UA were found of significant value. Among which, 8 shared metabolites were found of low level expression in both swine model and UA patients. Independent Student's t-test, principal component analysis (PCA), and hierarchicalcluster analysis (HCA) were orderly applied to comprehend inner rules of variables in the data. The 8 shared metabolites could take place of the 21 or 20 metabolites in classification of swine model with MI and UA patients, which could be considered as a bridge connecting the mechanism basis and macrosyndromes of swine model with MI and UA patients.


Enzyme immunoassay discrimination of a new angiotensin-converting enzyme (ACE) inhibitor, cilazapril, and its active metabolite.
Simple and sensitive enzyme immunoassays (EIAs), discriminating a new angiotensin-converting enzyme (ACE) inhibitor, cilazapril [9(s) - [1(s)-(ethoxycarbonyl)-3-phenylpropylamino]-octahydro-10-oxo-6H- pyridazo[1,2-a] [1,2]diazepine-1(s)carboxylic acid] and its active metabolite [9(s)-[1(s)-carboxy-3-phenylpropylamino]-octahydro-10-oxo-6H- pyridazo[1,2-a][1,2]diazepine-1(s)carboxylic acid] were developed for pharmacokinetic studies of this drug which is used as an antihypertensive agent. These assays can be performed directly on serum or plasma specimens without pretreatment. The EIA for cilazapril (prodrug) allowed the determination of as little as 30 pg/mL, while a 1000-times greater concentration of its active metabolite was required to achieve the same extent of inhibition. The EIA for the active metabolite exhibited a sensitivity and specificity similar to those of the prodrug. Plasma specimens from a human volunteer study and a marmoset subacute toxicity study were assayed by these two newly developed EIAs. The plasma levels of active metabolite determined by the EIA were compared with those assayed by radioenzymatic assay, and a good correlation was observed between them.


Sequence determinants in hypoxia-inducible factor-1alpha for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3.
Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor induced by hypoxia. Under normoxic conditions, site-specific proline hydroxylation of the alpha subunits of HIF allows recognition by the von Hippel-Lindau tumor suppressor protein (VHL), a component of an E3 ubiquitin ligase complex that targets these subunits for degradation by the ubiquitin-proteasome pathway. Under hypoxic conditions, this hydroxylation is inhibited, allowing the alpha subunits of HIF to escape VHL-mediated degradation. Three enzymes, prolyl hydroxylase domain-containing proteins 1, 2, and 3 (PHD1, -2, and -3; also known as HIF prolyl hydroxylase 3, 2, and 1, respectively), have recently been identified that catalyze proline hydroxylation of HIF alpha subunits. These enzymes hydroxylate specific prolines in HIF alpha subunits in the context of a strongly conserved LXXLAP sequence motif (where X indicates any amino acid and P indicates the hydroxylacceptor proline). We report here that PHD2 has the highest specific activity toward the primary hydroxylation site of HIF-1alpha. Furthermore, and unexpectedly, mutations can be tolerated at the -5, -2, and -1 positions (relative to proline) of the LXXLAP motif. Thus, these results provide evidence that the only obligatory residue for proline hydroxylation in HIF-1alpha is the hydroxylacceptor proline itself.


Influence of the use of complete denture adhesives on microbial adhesion and biofilm formation by single- and mixed-species.
To verify whether the Ultra Corega Cream and Corega Strip Denture Adhesive adhesives interfere in the microbial adhesion and biofilm formation by Candida albicans and Lactobacillus casei in single- and mixed-species settings, and observe whether synergistic or antagonistic relationships between these species occur. Specimens made from heat-polymerized acrylic resin (Lucitone 550) were fabricated (n = 144) with a circular shape and standardized roughness (3.0 μm ±0.3 Ra) and were divided into three groups: Without Adhesive (WA), with Ultra Corega Cream adhesive (CA) and Corega Strips adhesive (SA). These groups were divided into three subgroups each: C. albicans single-species, L. casei single-species and C. albicans with L. casei (mixed-species). Microbial adhesion and biofilm formation assays were performed in duplicate at four distinct experimental times (n = 8 per experimental condition). The amount of each microorganism on the surfaces of the specimens was observed by counting of the Colony Forming Units (CFU) per substrate. Additional specimens were characterized by Scanning Electron Microscopy (SEM), with 18 specimens being used in this analysis (n = 18), 2 per experimental condition (n = 2). Two-way ANOVA and Tukey's test for multiple comparisons were employed, using α≤0.05. L. casei (mixed-species) adhered more on the WA substrate than the CA, while C. albicans (single- and mixed-species) adhered more on the SA. C. albicans, both single- and mixed-species adhered more than the L. casei (single- and mixed-species), regardless of the substrate. L. casei (single-species) formed more biofilm on the WA, but in its mixed cultivation, it had no difference of growth among the tested situations. C. albicans (single- and mixed-species) formed more biofilm on the SA than the CA, and the fungus formed more biofilm when compared to L. casei. In general, whenever a species was compared in its single- and mixed-species situation, no statistically significant difference was observed. SEM of biofilm formation assays demonstrated that L. casei single-species WA formed more biofilm than when the adhesives tested were used, and C. albicans (both single- and mixed-species) formed more biofilm on the SA than on the CA. (1) The two denture adhesives tested increased the adhesion of C. albicans but not of L. casei; (2) biofilm formation by C. albicans (single- and mixed-species) was increased on the SA; (3) Relations of synergism or antagonism was not observed between the two microorganisms studied.


Estimating tests including subtests.
Current assessment studies often face a dilemma that arises from the necessity of a simultaneous unidimensional and multidimensional interpretation of a test. When, additional to the measurement of a single domain, subdomains of this domain are to be measured, one and the same data set will have to be analyzed unidimensionaly and multidimensionaly at the same time even though it is a contradiction of the theoretical assumptions underlying the analysis. This article, at first, describes the psychometric deficiencies typically going along with current analysis approaches. Subsequently, a subdimension model is proposed that explicitly allows for the existence of subdomains, or subdimensions, in a measured domain. Thereby, the model provides a means to obtain calibration results that suffer less from the deficiencies described and also allows for an item selection in the test development process that already considers the multidimensional structure of the test.


Inhibition by N-acetyl-L-cysteine of interleukin-6 mRNA induction and activation of NF kappa B by tumor necrosis factor alpha in a mouse fibroblastic cell line, Balb/3T3.
Redox-based modulation plays a role in transcriptional control of gene expression. In the present study, we investigated the possible role of reactive oxygen species in the induction of interleukin-6 (IL-6) mRNA and in increases in NF kappa B binding activity by tumor necrosis factor (TNF) alpha using a mouse fibroblastic cell line, Balb/3T3. Expression of IL-6 mRNA is known to be dependent upon NF kappa B that binds to the 5'-flanking region of the IL-6 gene. We found that: (i) TNF alpha increased IL-6 mRNA levels and this increase was inhibited by N-acetyl-L-cysteine (NAC), a scavenger of reactive oxygen species. (ii) NF kappa B binding activity in this cell line was also increased by TNF alpha, and the increase was inhibited in the presence of NAC. (iii) The treatment of cells with low doses of hydrogen peroxide increased the NF kappa B binding activity. (iv) Expression of a reporter gene in which the chloramphenicol acetyltransferase (CAT) gene was under the control of NF kappa B binding sites was induced by hydrogen peroxide. These results suggest that the induction of IL-6 mRNA is regulated by a mechanism involving reactive oxygen species and that NF kappa B, whose activity is sensitive to the cellular redox state, plays an important role in this induction in a fibroblastic cell line, Balb/3T3, stimulated with TNF alpha.


An Effective Treatment in the Austere Environment? A Critical Appraisal into the Use of Intra-Articular Local Anesthetic to Facilitate Reduction in Acute Shoulder Dislocation.
Acute shoulder dislocation is a common injury in the outdoor environment. The objective of this systematic review of the literature was to determine if intra-articular local anesthetic (IAL) is an effective treatment that could have prehospital application. A methodical search of MEDLINE, PubMed, and EMBASE databases targeted publications from January 1, 1990 until January 1, 2017. Eligible articles compared IAL with other analgesic techniques in patients 16 years or older experiencing acute glenohumeral dislocation. Reduction success, complications, and patient-reported outcome measures underwent comparison. All identified publications originated from the hospital setting. Procedural success rates ranged widely among randomized control trials comparing IAL with intravenous analgesia and sedation (IAL 48-100%, intravenous analgesia and sedation 44-100%). A pooled risk ratio [RR] favored intravenous analgesia and sedation (RR 0.91, 95% confidence interval [CI] 0.84-0.98), but there was significant inconsistency within the analysis (I2 = 75%). IAL provided lower complication rates (4/170, 2%) than intravenous analgesia and sedation (20/150, 13%) (RR 1.11, 95% CI 1.04-1.19, I2 = 63%). One trial found a clinically relevant reduction in visual analogue pain scores when comparing IAL against no additional analgesia in the first minute (IAL 21±13 mm; control 49±15 mm; P<0.001) and fifth minute (IAL 10±10 mm; control 40±14 mm, P<0.001) after reduction. The results suggest that IAL is an effective intervention for acute anterior shoulder dislocation that would have a place in the repertoire of the remote physician. Further research might be beneficial in determining the outcomes of performing IAL in the prehospital setting.


Sensing Technologies for Detection of Acetone in Human Breath for Diabetes Diagnosis and Monitoring.
The review describes the technologies used in the field of breath analysis to diagnose and monitor diabetes mellitus. Currently the diagnosis and monitoring of blood glucose and ketone bodies that are used in clinical studies involve the use of blood tests. This method entails pricking fingers for a drop of blood and placing a drop on a sensitive area of a strip which is pre-inserted into an electronic reading instrument. Furthermore, it is painful, invasive and expensive, and can be unsafe if proper handling is not undertaken. Human breath analysis offers a non-invasive and rapid method for detecting various volatile organic compounds thatare indicators for different diseases. In patients with diabetes mellitus, the body produces excess amounts of ketones such as acetoacetate, beta-hydroxybutyrate and acetone. Acetone is exhaled during respiration. The production of acetone is a result of the body metabolising fats instead of glucose to produce energy. There are various techniques that are used to analyse exhaled breath including Gas Chromatography Mass Spectrometry (GC-MS), Proton Transfer Reaction Mass Spectrometry (PTR-MS), Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS), laser photoacoustic spectrometry and so on. All these techniques are not portable, therefore this review places emphasis on how nanotechnology, through semiconductor sensing nanomaterials, has the potential to help individuals living with diabetes mellitus monitor their disease with cheap and portable devices.


Movements near the gate of a hyperpolarization-activated cation channel.
Hyperpolarization-activated cation (HCN) channels regulate pacemaking activity in cardiac cells and neurons. Like the related depolarization-activated K+ channels (Kv channels), HCN channels use an intracellular activation gate to regulate access to an inner cavity, lined by the S6 transmembrane regions, which leads to the selectivity filter near the extracellular surface. Here we describe two types of metal interactions with substituted cysteines in the S6, which alter the voltage-controlled movements of the gate. At one position (L466), substitution of cysteine in all four subunits allows Cd2+ ions at nanomolar concentration to stabilize the open state (a "lock-open" effect). This effect depends on native histidines at a nearby position (H462); the lock-open effect can be abolished by changing the histidines to tyrosines, or enhanced by changing them to cysteines. Unlike a similar effect in Kv channels, this effect depends on a Cd2+ bridge between 462 and 466 in the same subunit. Cysteine substitution at another position (Q468) produces two effects of Cd2+: both a lock-open effect and a dramatic slowing of channel activation-a "lock-closed" effect. The two effects can be separated, because the lock-open effect depends on the histidine at position 462. The novel lock-closed effect results from stabilization of the closed state by the binding of up to four Cd2+ ions. During the opening conformational change, the S6 apparently moves from one position in which the 468C cysteines can bind four Cd2+ ions, possibly as a cluster of cysteines and cadmium ions near the central axis of the pore, to another position (or flexible range of positions) where either 466C or 468C can bind Cd2+ in association with the histidine at 462.


Effect of temperature on developmental rate of Sesamia cretica (Lepidoptera: Noctuidae) immature stages.
Effect of temperature on development of pink stem borer, Sesamia cretica Lederer, was studied at eight constant temperatures (15, 18, 20.5, 24, 27, 30, 34, and 38°C), a photoperiod of 16:8 (L:D) h, and 50-60% rela\tive humidity. The larvae of pink stem borer were reared on cutting stems of maize. The results showed that temperature had statistically significant effect on developmental times of the all developmental stages. The most commonly used six nonlinear models applied for modeling developmental rate of immature stages as a function of temperature. Evaluation of the models fit to data took place based on the coefficient of determination, residual sum of squires, adjusted coefficient of determination, and Akaike information criterion. Besides statistical criteria, biological significance was used to determine the best model. All the examined models statistically fit the data well. In addition, Briere-2 was selected as the best model considering biological significance of the estimated values for the biologically interpretable parameters of models. Based on the results, the values of the lower temperature threshold were 10.82, 11.81, 9.35, and 10.67°C, the optimal temperature were 35.50, 31.80, 33.35, and 32.22°C, and the upper temperature threshold were 38.93, 39.19, 37.41, and 36.55°C, for incubation period, larva, pupa, and overall immature stages of pink stem borer, respectively.


Competency assessment in the clinical microbiology laboratory.
The laboratory comprises an invaluable part of the total health care provided to patients. Competency assessment is one method by which we can verify that our employees are competent to perform laboratory testing and report accurate and timely results. To derive the greatest benefit from the inclusion of competency assessment in the laboratory, we must be sure that we are addressing areas where our efforts can be best utilized to optimize patient care. To be competent, an employee must know how to perform a test, must have the ability to perform the test, must be able to perform the test properly without supervision, and know when there is a problem with the test that must be solved. In some cases, competency assessment protocols may demonstrate areas of competence but can fail to disclose incompetence. For example, challenges of low-complexity tasks (such as reading the technical procedure manual) are inferior to challenges that measure understanding and execution of a protocol, and poorly designed competency challenges will probably not detect substandard laboratory performance. Thus, if we are to receive the greatest benefit from our competency assessment programs, which may be time-consuming for the supervisors and the staff as well, we must not only meet the letter of the law but also find a way to make these assessments meaningful, instructive, and able to detect areas of concern. As we address competency assessment in our laboratories, we must understand that when done properly, competency assessment will reward our organizations and assist us in providing the best possible care to our patients.


Risk factors for Crohn's disease of the neo-small intestine in ulcerative colitis patients with total proctocolectomy and primary or secondary ileostomies.
De novo Crohn's disease (CD) of the neo-small intestine in ulcerative colitis (UC) patients after total proctocolectomy (TPC) is a new disease entity, which may persist even after a secondary diverting permanent ileostomy for pouch failure. We sought to compare outcomes of primary ileostomy (PI, i.e., stoma created after colectomy without trying of ileal pouch) and secondary ileostomy (SI, i.e., stoma created after pouch failure) and to evaluate factors associated with the development of CD of the neo-small intestine proximal to ileostomy. A total of 123 eligible patients were identified from our Pouch Center Registry (PI group, n = 57 and SI group, n = 66). Demographics, clinical features and outcomes (CD of theneo-small intestine, non-CD related strictures, requirement of CD-related medications use, ileostomy-associated hospitalization, ileostomy failure with stoma revision/relocation, and shortgut syndrome) were compared. Step-wise logistic regression models were performed. The median follow-up for the whole cohort was 5.0 (2.0–12.0) years. Younger age at diagnosis and surgery, family history of IBD, toxic megacolon/fulminant colitis, pre-diversion severe diarrhea, prediversion anti-TNF biological therapy, arthralgia/arthropathy and staged surgery were more common in the SI group (p < 0.05). In multivariate analysis, the presence of SI [odds ratio (OR), 8.23; 95% confidence interval (CI), 2.43–27.85], family history of IBD (OR, 9.14; 95% CI, 3.13–26.69), and pre-diversion of weight loss (OR, 3.72; 95% CI, 1.23–11.21) were contributing factors for developing CD of the neo-small intestine. CD of the neo-small intestine in stoma patients was associated with the presence of SI, family history of IBD, and pre-diversion poor nutrition status. Patients with secondary ileostomy due to pouch failure should be carefully monitored. Aggressive medical, endoscopic or surgical therapy may be needed in patients at risk, before permanent diversion.


Bilateral spastic cerebral palsy--a collaborative study between southwest Germany and western Sweden. III: Aetiology.
In this third report from the collaborative study of children with bilateral spastic cerebral palsy born between 1975 and 1986, aetiology was analysed. Evidence for a prenatal aetiology increased with gestational age, whereas evidence for a peri-/neonatal aetiology decreased. The largest subgroup, the leg-dominated subtype, showed the same distribution of aetiology as the total group. A prenatal aetiology was found mainly among term and moderately preterm children with a four-limb-dominated subtype; a peri-/neonatal aetiology among very preterm children with a three- or four-limb-dominated subtype or among term children with a dyskinetic-spastic subtype. The findings support the hypothesis generated from the authors' epidemiological results of a peri-/neonatal aetiology being predominant among preterm, and a prenatal aetiology among term, children with bilateral spastic cerebral palsy.


Assessment of body elimination attitude.
Constructed a 26-item Likert format Body Elimination Attitude Scale with good internal consistency and temporal stability (N = 60). Factor analysis yielded seven factors labeled Fecal Smell, Personal Hygiene, Sight, Dirty Hair, Animal Feces, Mucous-like Discharge, and Sound. Both the prominence of items that pertained to defecation and the positive association of the Scale with a measure of obsessive personality-anal character were viewed as consistent with psychoanalytic theory. Correlations with psychometric instruments revealed greater body elimination disgust to be associated with psychopathology. Youth, lesser education, having fewer children, being female, and lesser income also were associated with greater disgust.


Flipping the Objective Structured Clinical Examination: A Teaching Innovation in Graduate Nursing Education.
Objective evaluation of distance-based family nurse practitioner (FNP) students can be challenging. One FNP program piloted a teaching innovation, the video-enhanced objective structured clinical examination (VE-OSCE) or "flip" of the traditional face-to-face OSCE, to assess student clinical performance in a controlled online environment using a teleconferencing platform. This project sought to assess the VE-OSCE design, implementation, and ability to identify FNP student learning needs.


Theory of minimum spanning trees. II. Exact graphical methods and perturbation expansion at the percolation threshold.
Continuing the program begun by the authors in a previous paper, we develop an exact low-density expansion for the random minimum spanning tree (MST) on a finite graph and use it to develop a continuum perturbation expansion for the MST on critical percolation clusters in space dimension d . The perturbation expansion is proved to be renormalizable in d=6 dimensions. We consider the fractal dimension D(p) of paths on the latter MST; our previous results lead us to predict that D(p)=2 for d>d(c)=6 . Using a renormalization-group approach, we confirm the result for d>6 and calculate D(p) to first order in epsilon=6-d for d<6 using the connection with critical percolation, with the result D(p)=2-epsilon/7+O(epsilon(2)) .


Spontaneous rectus sheath hematoma: an analysis of 15 cases.
Spontaneous rectus sheath hematoma (RSH) is an uncommon and frequently misdiagnosed cause of acute abdominal pain. The purpose of this study is to present our experiences in the diagnosis and treatment of spontaneous RSH. This is a retrospective study of the medical histories of 15 patients admitted to our emergency surgery unit between January 2000 and July 2009 and diagnosed with spontaneous RSH (12 females, 3 males; mean age, 64.5 years; range, 20-79 years). All cases presented with acute abdominal pain or abdominal wall mass, or both. Eleven of the cases (73%) had been receiving some form of anticoagulation therapy. The leading indications for anticoagulation and/or anti-platelet therapy were atrial fibrillation in 5 patients (33%) and mitral valve replacement in 3 patients (20%). Diagnosis was made by abdominal ultrasonography and/or computerized tomography in 14 patients (93%). Twelve (80%) of the 15 patients were discharged uneventfully after conservative management following a mean hospital stay of 8.8 days (range, 3-24 days). The mortality rate was 20%. Spontaneous RSH must be suspected in patients with advanced age who are using anticoagulation medications and present with acute abdominal pain. Early diagnosis permits conservative management and avoids unnecessary surgical interventions.


Red yeast rice lowers cholesterol in physicians - a double blind, placebo controlled randomized trial.
In recent years, red yeast rice (RYR) supplements have been marketed aggressively as a natural way to lower cholesterol; however, the large majority of commercially available products have not been studied according to current research standards. In a double blind placebo controlled randomized trial, 52 physicians and their spouses with a total cholesterol level of > 200 mg/dL were randomly allocated to receive a RYR extract or placebo for 8 weeks. As a primary outcome measure, we compared the before-after difference in lipid levels between both groups. As secondary outcome measures we looked at side-effects, CK elevation and a change in cardiovascular risk. LDL (low density lipoprotein) cholesterol was lowered with 36 mg/dL (22%) and total cholesterol with 37 mg/dL (15%) in the intervention group. This result was statistically significant as compared to the control group, in which no reduction in total cholesterol and LDL was observed (p < 0.001). There was no marked difference in CK (creatine kinase)-elevation or reported side-effects between study groups. In 5/31 participants in the intervention group, the lipid lowering effect resulted in lower cardiovascular risk as measured with SCORE (Systematic COronary Risk Evaluation). The RYR formulation under study was effective in lowering cholesterol and LDL cholesterol in this study population. RYR therapy may be an attractive and relatively well studied alternative in patients who are intolerant for statins or who have objections against pharmacological lipid lowering. However, consumers need to be warned that the actual content of commercially available preparations is not assured by governmental regulations, which raises effectiveness and safety issues. Clinicaltrials.gov, nr: NCT01558050.


Use of chimerism analysis after allogeneic stem cell transplantation: Belgian guidelines and review of the current literature.
Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option in both adult and pediatric patients with malignant and non-malignant hematological diseases. Chimerism analysis, which determines the donor or recipient origin of hematopoietic cells in HSCT recipients, is an essential aspect of post-HSCT follow-up.Objectives: To review the current literature and develop Belgian consensus guidelines for the use of chimerism analysis in the standard of care after allogeneic HSCT.Methods: Non-systematic review of the literature in consultancy with the members of the BHS transplantation committee.Results: Clinical application with regards to prediction of graft failure or relapse as well as cell source are reviewed. A consensus guideline on the use of chimerism analysis after HSCT is presented.Conclusion: Monitoring of the dynamics or kinetics of a patient's chimerism status by serial analysis at fixed time points, as well as on suspicion of relapse or graft failure, is needed to monitor engraftment levels, as well as disease control and possible relapse.


Blink reflex in motor neuron disease.
The aim of the study was to analyse the diagnostic value of blink reflex (BR) in motor neuron disease (MND). We studied 25 patients with MND including amyotrophic lateral sclerosis (ALS) in 18 patients, primary muscular atrophy (PMA) in 4 patients, and primary lateral sclerosis (PLS) in 3 patients and 12 healthy volunteers. The blink reflex was obtained in typical way. In ALS group, statistically significant increase in latency and decreased amplitude of R2 responses were found compared to the control group (p < 0.05), whereas BR in patients with PLS and PMA was within normal limits. The presence of low amplitude of R2 responses in patients with ALS may suggest loss of lower brainstem neurons connecting trigeminal and facial system, and probably also decreased facilitator effect of central nervous system on reticular formation in the brainstem.


Expression of PDGF beta-receptors in human meningioma cells.
Meningioma is a generally benign tumor derived from arachnoid tissue. We have investigated the presence of functionally active PDGF-receptors on human meningioma cells in culture. Tumor samples were obtained from 3 surgically removed benign meningiomas and normal arachnoid tissue from an autopsy case. Binding studies were performed by using 125I-labelled recombinant PDGF-AA and PDGF-BB. Only 125I-PDGF-BB showed specific binding to all tumor-cell cultures after incubation of cells for 2 hr at 4 degrees C. Effects of PDGF-AA and PDGF-BB on DNA synthesis were measured as 3H-thymidine incorporation during 48 hr of labelling cells maintained in Eagle's minimum essential medium 0.5% fetal calf serum. PDGF-BB but not PDGF-AA stimulated DNA synthesis in all 3 tumor-cell cultures. Total cellular RNA was analyzed by Northern blotting and hybridization with a 32P-labelled human PDGF beta-receptor probe, and PDGF beta-receptor mRNA was found in both tumor and arachnoid cell cultures. Furthermore, PDGF beta-receptor mRNA was shown to be present in 2 meningioma biopsies and immunohistochemical staining revealed that PDGF beta-receptors are present in meningioma and arachnoid tissues in vivo. It appears that a possible way of maintaining human meningioma cell growth in vivo is through activation of PDGF beta-receptors.