Long-term benzodiazepine and Z-drugs use in England: a survey of general practice [corrected].
Current British National Formulary (BNF) guidelines state that benzodiazepines and zolpidem, zopiclone, and zaleplon, commonly known as Z-drugs (BZD), be prescribed for no more than 4 weeks, although anecdotal data suggest that many patients are prescribed BZDs for much longer. As there are no recent, evidence-based estimates of long-term (>12 months) BZD use in the UK, the scale of this potential problem is unknown. To produce the first reliable, evidence-based estimate of long-term BZD use in the UK. Estimates of UK long-term BZD use were projected from data obtained from a survey conducted in 2014-2015 by the Bridge Project, a prescribed-drug withdrawal support charity in the North of England (Bradford). Percentages of long-term users of BZD were derived from the survey, by sampling primary care GP surgeries with around 100 000 registered patients, and these were applied to UK-wide NHS patient numbers. The data were filtered to exclude the very young and old, and those with other health issues. The mean percentage of registered patients prescribed BZDs for more than a year in the survey sample is 0.69% (95% confidence interval [CI] = 0.54 to 0.84). Applying this value to national patient numbers yields a mean projection of 296 929 (95% CI = 232 553 to 361 305) long-term users of BZD in the UK. The data also suggest that as many as 119 165 of these patients may be willing to accept prescribed drug dependency withdrawal services. More than a quarter of a million people in the UK are likely to be taking highly dependency-forming hypnotic medication far beyond the recommended time scales. As there is evidence that long-term use of BZDs causes adverse physiological and neurological effects, and protracted withdrawal (with associated complications), this represents a serious public health problem.


Neighbourhood social capital and common mental disorder: testing the link in a general population sample.
General population multilevel studies of social capital and mental health are few in number. This multilevel study examined external measures of neighbourhood social capital and common mental disorders (CMD). Main effects and stress buffering models were tested. Based on data from over 9000 residents in 239 neighbourhoods in England and Scotland, there was no evidence of a main effect of social capital. For people living in deprived circumstances only, associations between neighbourhood social capital and CMD were seen. Elements of bridging social capital (contact amongst local friends) were associated with lower reporting of CMD. Elements of bonding social capital (attachment to neighbourhood) were associated with higher reporting of CMD. Findings provide some support for the hypothesis that social capital may protect against CMD, but indicate that initiatives should be targeted to deprived groups, focus on specific elements of social capital and not neglect the important relationship between personal socioeconomic disadvantage and CMD.


[Minimally invasive direct coronary artery bypass for ischemic heart disease associated with preoperative severe complications].
Our experiences of minimally invasive direct coronary artery bypass (MIDCAB) were reported with review of literatures. Patient #1 was a 69 years-old man with left main lesion associated with cerebral infarction and impaired renal function. Preoperative CT examination showed calcified ascending aorta. There was no significant lesions in the large right coronary artery and the circumflex was small. The patient underwent MIDCAB via minithoracotomy on the fourth intercostal space with left internal thoracic artery (ITA) to left anterior descending artery (LAD). The patient was weaned from ventilator 3 hours after the operation and his postoperative course was uneventful. Patient #2 was a 80 years-old man with acute myocardial infarction requiring intraaortic balloon pumping (IABP) due to significant stenosis in the right coronary artery and left main lesion associated with chronic hemodialysis due to renal failure. The right coronary artery was dilated by balloon angioplasty at the time of emergency coronary angiogram. However, the emergent operation was required because of the left main lesion. The circumflex was relatively small and because of severe complication, MIDCAB was selected to improve his condition. He underwent MIDCAB via minithoracotomy. The heart was enlarged because of congestive heart failure and left inferior epigastric artery was used to extend the length of the left ITA. The composite graft of ITA and IEA was anastomosed to the LAD under beating heart. The IABP was removed 8 hours after the operation and his postoperative course was uneventful. The MIDCAB for coronary artery bypass was first reported by Benetti et al in 1995 and the procedure seemed to be very effective for preventing postoperative complications in selected patients as seen in ours.


Psychotic disorders in MS: population-based evidence of an association.
Administrative data from a Canadian province were accessed to assess the association of psychotic disorders with multiple sclerosis (MS). Physician-assigned ICD-9-CM codes were used to classify MS and psychotic disorder status. A significant association was observed. Additional research is needed to determine the clinical importance and treatment needs of this population.


PI 3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning.
We investigated whether phosphatidylinositol 3-kinase (PI3K) might regulate mitochondrial permeability transition pore (mPTP) opening in hearts reperfused with either low pressure or postconditioning. Male Wistar rat hearts (n=72) were perfused according to the Langendorff technique, exposed to 30 min of ischemia, and assigned to one of the following groups: (1) reperfusion with normal pressure (NP; 100 cm H2O), (2) reperfusion with low pressure (LP; 70 cm H2O), or reperfusion with postconditioning, i.e. 3 episodes of 30 s reperfusion followed by 30 s of ischemia (PostC). Hearts received either the PI3K inhibitors wortmannin or LY294002, or vehicle at the onset of the 60 min reperfusion. Postischemic functional recovery was assessed by rate-pressure product (RPP), and irreversible injury by lactate dehydrogenase (LDH), creatine kinase (CK) and troponin I (TnI) release. Mitochondria were isolated from the reperfused myocardium, and Ca2+-induced mPTP opening was measured using a potentiometric method. Functional recovery was significantly improved in LP and PostC hearts with RPP averaging 13,880+/-810 (LP) and 17,130+/-900 mm Hgxbeats/min (PostC) versus 6450+/-500 mm Hgxbeats/min in NP hearts (p<0.01). LDH release averaged 230+/-30 and 145+/-15 IU/h/g of myocardial tissue in LP and PostC versus 340+/-10 IU/h/g in NP (p<0.05). Wortmannin and LY294002 prevented both RPP improvement and decrease in LDH, CK, and TnI release in LP and PostC groups. The Ca2+ load required to induce mPTP opening averaged 58+/-3 and 52+/-1 nmol/mg mitochondrial proteins in LP and PostC groups, respectively, versus 35+/-4 nmol/mg in the NP group (p<0.01). Wortmannin and LY294002 prevented the beneficial effect in both the LP and PostC groups. These results suggest that PI3K regulates the opening of the mitochondrial permeability transition pore in rat hearts reperfused with low pressure or postconditioning.


Brain Imaging Techniques: Improving the Quality.
Image quality is a factor of the utmost importance in nuclear medicine. Regardless of what type of scan is being done, technologists should be diligent in how images are being acquired. With respect to brain imaging, there can be challenges that the technologist must understand how to navigate and overcome. This continuing education article, focusing mainly on brain SPECT (particularly with 123I-ioflupane) and brain 18F-FDG PET/CT, will help technologists better understand how artifacts occur and how imaging techniques can affect image quality.


Occurrence of a new microsporidium in the skeletal muscle of the flying fish Cypselurus pinnatibarbatus japonicus (Exocoetidae) from Yakushima, Japan.
A new microsporidium was observed in the flying fish Cypselurus pinnatibarbatus japonicus (Franz) (Exocoetidae) from Yakushima, Japan. Visual examination revealed the microsporidium to form white elongate nodules in the host's trunk muscle. Monomorphic spores were ovoid to pyriform in shape, with average dimensions of 4.1 x 2.2 microm and possessing a polar tube describing 13-15 coils. Histological observations showed that each parasite focus of infection was encapsulated by a host-produced fibrous membrane. The presence of sporophorous vesicles was not clearly determined. Ribosomal DNA sequence analyses showed the microsporidium to be discrete from other known fish muscle-infecting species and to be most closely related to a clade comprising the Pleistophoridae and Glugea spp. The parasite is provisionally placed as Microsporidium cypselurus sp. n.


Identifying and assessing highly hazardous drugs within quality risk management programs.
Historically, pharmaceutical industry regulatory guidelines have assigned certain active pharmaceutical ingredients (APIs) to various categories of concern, such as "cytotoxic", "hormones", and "steroids". These categories have been used to identify APIs requiring segregation or dedication in order to prevent cross-contamination and protect the quality and safety of drug products. Since these terms were never defined by regulatory authorities, and many novel pharmacological mechanisms challenge these categories, there is a recognized need to modify the historical use of these terms. The application of a risk-based approach using a health-based limit, such as an acceptable daily exposure (ADE), is more appropriate for the development of a Quality Risk Management Program (QRMP) than the use of categories of concern. The toxicological and pharmacological characteristics of these categories are discussed to help identify and prioritize compounds requiring special attention. Controlling airborne concentrations and the contamination of product contact surfaces in accordance with values derived from quantitative risk assessments can prevent adverse effects in workers and patients, regardless of specific categorical designations to which these APIs have been assigned. The authors acknowledge the movement away from placing compounds into categories and, while not yet universal, the importance of basing QRMPs on compound-specific ADEs and risk assessments. Based on the results of a risk assessment, segregation and dedication may also be required for some compounds to prevent cross contamination during manufacture of APIs.


Lipid exchange in crystal-confined fatty acid binding proteins: X-ray evidence and molecular dynamics explanation.
Fatty acid binding proteins (FABPs) are responsible for the long-chain fatty acids (FAs) transport inside the cell. However, despite the years, since their structure is known and the many studies published, there is no definitive answer about the stages of the lipid entry-exit mechanism. Their structure forms a β -barrel of 10 anti-parallel strands with a cap in a helix-turn-helix motif, and there is some consensus on the role of the so-called portal region, involving the second α -helix from the cap ( α 2), β C- β D, and β E- β F turns in FAs exchange. To test the idea of a lid that opens, we performed a soaking experiment on an h-FABP crystal in which the cap is part of the packing contacts, and its movement is strongly restricted. Even in these conditions, we observed the replacement of palmitic acid by 2-Bromohexadecanoic acid (Br-palmitic acid). Our MD simulations reveal a two-step lipid entry process: (i) The travel of the lipid head through the cavity in the order of tens of nanoseconds, and (ii) The accommodation of its hydrophobic tail in hundreds to thousands of nanoseconds. We observed this even in the cases in which the FAs enter the cavity by their tail. During this process, the FAs do not follow a single trajectory, but multiple ones through which they get into the protein cavity. Thanks to the complementary views between experiment and simulation, we can give an approach to a mechanistic view of the exchange process.


The worst of times, the best of times : psychotherapy in the 1990s.
The author discusses the state of the art of psychotherapy at the brink of the new decade. The theme of the 1990s is rapprochement, the bridging of divisive aspects of the field. Four major manifestations of increased detente are explored: convergence of mind and brain, collaboration of research and public policy, coordination of economic constraints and ethical standards, and connection between psychopathology and therapeutic practice. Factors of major importance for the future of psychotherapy are the impact of the neurosciences on psychological phenomena, the role of the computer in human simulation, the socioeconomic influence of government and third-party payers on the direction of treatment, and the utilization of clinical practice in devising new diagnostic dimensions.


Age-related shifts in gut microbiota contribute to cognitive decline in aged rats.
Cognitive function declines during the aging process, meanwhile, gut microbiota of the elderly changed significantly. Although previous studies have reported the effect of gut microbiota on learning and memory, all the reports were based on various artificial interventions to change the gut microbiota without involvement of aging biological characteristics. Here, we investigated the effect of aged gut microbiota on cognitive function by using fecal microbiota transplantation (FMT) from aged to young rats. Results showed that FMT impaired cognitive behavior in young recipient rats; decreased the regional homogeneity in medial prefrontal cortex and hippocampus; changed synaptic structures and decreased dendritic spines; reduced expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate receptor NR1 subunit, and synaptophysin; increased expression of advanced glycation end products (AGEs) and receptor for AGEs (RAGE). All these behavioral, brain structural and functional alterations induced by FMT reflected cognitive decline. In addition, FMT increased levels of pro-inflammatory cytokines and oxidative stress in young rats, indicating that inflammation and oxidative stress may underlie gut-related cognitive decline in aging. This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function.


Dynamical states in driven colloidal liquid crystals.
We study a model colloidal liquid crystal consisting of hard spherocylinders under the influence of an external aligning potential by Langevin dynamics simulation. The external field that rotates in a plane acts on the orientation of the individual particles and induces a variety of collective nonequilibrium states. We characterize these states by the time-resolved orientational distribution of the particles and explain their origin using the single particle behavior. By varying the external driving frequency and the packing fraction of the spherocylinders we construct the dynamical state diagram.


Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive-compulsive disorder as an example of overlapping clinical and genetic heterogeneity.
Individuals with obsessive-compulsive disorder (OCD) have also been shown to have comorbid lifetime diagnoses of major depressive disorder (MDD; rates greater than 70%), bipolar disorder (rates greater than 10%) and other anxiety disorders (e.g. panic disorder, post-traumatic stress disorder (PTSD)). In addition, overlap exists in some common genetic variants (e.g. the serotonin transporter gene (SLC6A4), the brain-derived neurotrophic factor (BDNF) gene), and rare variants in genes/chromosomal abnormalities (e.g. the 22q11 microdeletion syndrome) found across the affective/anxiety disorder spectrums. OCD has been proposed as a possible independent entity for DSM-5, but by others thought best retained as an anxiety disorder subtype (its current designation in DSM-IV), and yet by others considered best in the affective disorder spectrum. This review focuses on OCD, a well-studied but still puzzling heterogeneous disorder, regarding alterations in serotonergic, dopaminergic and glutamatergic neurotransmission in addition to other systems involved, and how related genes may be involved in the comorbidity of anxiety and affective disorders. OCD resembles disorders such as depression, in which gene × gene interactions, gene × environment interactions and stress elements coalesce to yield OC symptoms and, in some individuals, full-blown OCD with multiple comorbid disorders.


Intestinal Flora: A Potential Mechanism by Which Yinlai Decoction Treats Lipopolysaccharide-Induced Pneumonia.
We intended to explore the mechanism of Yinlai decoction in the treatment of lipopolysaccharide (LPS)-induced pneumonia from the perspective of intestinal flora. Thirty Sprague-Dawley rats were randomly assigned to the blank control group (N), the pneumonia group (P), and the Yinlai decoction group (PT). The rat pneumonia model was established using LPS inhalation (0.5 mg/mL, 5 mL, 30 min/day, 3 days). Yinlai decoction was administered intragastrically (2 mL/100 g, 3 days). Lung tissue pathology, organ indexes, serum inflammatory factors, tumor necrosis factor-alpha (TNF-α), and intestinal flora changes were measured. Lung tissue inflammation was prevented by Yinlai decoction. IL-6 levels showed a higher tendency to be higher, and IL-12 and TNF-α were significantly higher in the PT group than in the P group. The structure of the intestinal flora in the P differed from that in the N. The relative abundance of 10 out of 12 microflora was significantly higher in the P group than in the N and PT groups. In the PT group, the structure and the distribution of microbial groups were like those of the N group. Yinlai decoction inhibited LPS-induced lung and systemic inflammation in rats and may help the intestinal flora restore equilibrium by inhibiting the colonization of pathogenic bacteria and adjusting the ratio between probiotics and pathogenic bacteria. Intestinal flora may serve as a mediator of Yinlai decoction's effect on LPS-induced pneumonia.


An educational visual resource to support understanding of liquid-liquid phase separation.
In collaboration with educators and researchers, we created an online resource called Phase Separation 101 to help undergraduate students understand the basics of liquid-liquid phase separation, an emerging and complex concept in cell biology for which visual resources are still scarce. This work presents the workflow and visual communication strategies that we followed to build scientifically accurate visualizations of dynamic processes.


Profiling and screening analysis of 27 aromatic amino acids by capillary electrophoresis in dual modes.
An efficient capillary electrophoretic (CE) profiling and screening system based on dual modes of capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC) was developed for the simultaneous determination of 23 nonprotein amino acids (NPAAs) and 4 protein amino acids with aromatic moiety. It involves separation by an uncoated fused-silica capillary under phosphoric acid buffer in CZE mode and by another uncoated fused-silica capillary under neutral sodium dihydrogen phosphate buffer containing sodium dodecyl sulfate in MEKC mode. Migration orders of the amino acids studied on the two separation modes under each optimum condition were very different. The repeatability of migration times measured by the CZE and MEKC was found to be better than 4.8 and 3.4%, respectively, thereby enabling to cross-check the identification of each amino acid. The method linearity and limit of detection of the CZE for each amino acid were found to be adequate for the assay of aromatic amino acids. When the present CE profiling and screening analysis in dual modes was applied to plant seeds, NPAAs such as mimosine from Mimosa pudica Linné, and 2-phenylglycine from Lindera erythrocarpa Makino were positively detected along with tryptophan, phenylalanine and tyrosine.


The application of scanning electron microscopy to the study of the cytoskeleton of cells in culture.
This paper reviews the methods available for studying the structural organization of the cytoskeleton of cells in culture. These are transmission electron microscopy of whole cells, immunofluorescence, and detergents extraction procedures. Published methods for detergent extraction are critically reviewed with special emphasis on those factors that are most relevant for the preparation of cytoskeletons for observation by scanning electron microscopy. These include the type of detergent, the use of chemical crosslinking reagents or specially formulated buffers to stabilize the cytoskeleton during extraction, the osmotic and salt composition of the extraction medium, the use of cool sputter coaters, and the application of minimal amounts of metal during coating. Finally, examples are given of the types of information about the three dimensional organization of the cytoskeleton that can be obtained by SEM.


Anatomical Study of the Innervation of Anterior Knee Joint Capsule: Implication for Image-Guided Intervention.
The knee joint is the most common site of osteoarthritis. While joint replacement is considered an ultimate solution, radiofrequency denervation may be contemplated in some cases. Radiofrequency ablation requires precise localization of the articular branches innervating the joint capsule. The objective of this cadaveric study was to determine the source, course, relationships, and frequency of articular branches innervating the anterior knee joint capsule. Fifteen knees were meticulously dissected. The number and origin of the articular branches were recorded, and their distribution defined by quadrants. Their relationships to anatomical landmarks were identified. The articular branches terminated in 1 of the 4 quadrants with minimal overlap. In all specimens, the superolateral quadrant was innervated by the nerve to vastus lateralis, nerve to vastus intermedius, superior lateral genicular and common fibular nerves; inferolateral by the inferior lateral genicular and recurrent fibular nerves; superomedial by the nerve to vastus medialis, nerve to vastus intermedius and superior medial genicular nerve; and inferomedial by the inferior medial genicular nerve. In 3 specimens, the inferomedial quadrant also received innervation from the infrapatellar branch of saphenous nerve. All articular branches except the nerves to vastus lateralis and medialis course at the periosteal level. The frequency map of the articular branches provides an anatomical basis for the development of new clinical protocols for knee radiofrequency denervation and perioperative pain management.


Idiopathic Spinal Subarachnoid Hemorrhage: A Case Report and Review of the Literature.
Study Design Case report. Objective Spinal subarachnoid hemorrhage (SSAH) makes up less than 1.5% of all the cases of subarachnoid hemorrhage. Most cases of spontaneous SSAH occur in association with coagulopathy, lumbar punctures, or minor trauma. Idiopathic SSAH is extremely rare with only 17 cases published. Idiopathic SSAH presents a diagnostic dilemma, and the appropriate investigations and treatment remain a matter of controversy. We report a case of idiopathic SSAH and a review of the literature regarding its clinical presentation, diagnosis, and treatment. Methods A 73-year-old woman presented to the emergency department after spontaneously developing severe right leg and lower back pain while bending over to vomit. After a review of the patient's history and examination, the magnetic resonance imaging (MRI) of the thoracolumbar spine revealed T1 hyperintensity and T2 hypointensity, a diffusion-restricted collection at the T11-T12 level, and a posterior collection from L3 to S1 producing a mild displacement of the thecal sac. Results The patient was taken for an L5 laminectomy. Intraoperatively, rust-colored, xanthochromic fluid was drained from the subarachnoid space, confirming SSAH. The thecal sac was decompressed. The cultures and Gram stains were negative. Computer tomography (CT) and CT angiography of the brain were normal. She recovered postoperatively with resolution of the pain and no further episodes of hemorrhage after 2 years of follow-up. Repeat thoracolumbar MRI, selective spinal angiogram, and six-vessel cerebral angiogram did not reveal pathology. Conclusion We suggest a clinical algorithm to aid in the diagnosis and management of such patients.


Validation of a commercial dry-form broth microdilution device (Sensititre) for testing tedizolid, a new oxazolidinone.
Tedizolid, a novel oxazolidinone antibacterial with potent activity against a wide range of Gram-positive pathogens, was recently approved by regulatory authorities for the treatment of acute bacterial skin and skin structure infections. A commercial broth microdilution device (Sensititre; Thermo Fisher Scientific) was validated using 285 selected Gram-positive isolates, and the device was documented to have 100.0% essential and categorical agreement with reference MIC results and excellent MIC endpoint reproducibility.


The interplay between depression and tuberculosis.
Depression is a major mental health condition and is expected be the most debilitating and widespread health disorder by 2030. Tuberculosis (TB) is also a leading cause of morbidity and mortality worldwide and interestingly, is a common comorbidity of depression. As such, much attention has been paid to the association between these 2 pathologies. Based on clinical reports, the association between TB and depression seems to be bidirectional, with a substantial overlap in symptoms between the 2 conditions. TB infection or reactivation may precipitate depression, likely as a consequence of the host's inflammatory response and/or dysregulation of the hypothalamic-pituitary-adrenal axis. Nevertheless, few studies have considered whether patients with depression are at a higher risk for TB. In this review, we discuss the hypotheses on the association between depression and TB, highlighting the immuno-inflammatory response and lipid metabolism as potential mechanisms. Improving our understanding of the interplay between these 2 disorders should help guide TB clinical care and prevention both in patients with comorbid depression and in the general population.


Pidotimod exacerbates allergic pulmonary infection in an OVA mouse model of asthma.
Pidotimod is a synthetic dipeptide with biological and immuno‑modulatory properties. It has been widely used for treatment and prevention of recurrent respiratory infections. However, its impact on the regulation of allergic pulmonary inflammation is still not clear. In the current study, an ovalbumin (OVA)‑induced allergic asthma model was used to investigate the immune‑modulating effects of pidotimod on airway eosinophilia, mucus metaplasia and inflammatory factor expression compared with dexamethasone (positive control). The authors determined that treatment with pidotimod exacerbated pulmonary inflammation as demonstrated by significantly increased eosinophil infiltration, dramatically elevated immunoglobulin E production, and enhanced T helper 2 response. Moreover, treatment failed to attenuate mucus production in lung tissue, and did not reduce OVA‑induced high levels of FIZZ1 and Arg1 expression in asthmatic mice. In contrast, administration of dexamethasone was efficient in alleviating allergic airway inflammation in OVA‑induced asthmatic mice. These data indicated that pidotimod as an immunotherapeutic agent should be used cautiously and the effectiveness for controlling allergic asthma needs further evaluation and research.


An assessment of the toxicological significance of anthropogenic contaminants in Canadian arctic wildlife.
Anthropogenic contaminants have been a concern in the Canadian arctic for over 30 years due to relatively high concentrations of bioaccumulating and biomagnifying organochlorine contaminants (OCs) and toxic metals found in some arctic biota and humans. However, few studies have addressed the potential effects of these contaminants in Canadian arctic wildlife. Prior to 1997, biological effects data were minimal and insufficient at any level of biological organization. The present review summarizes recent studies on biological effects related to contaminant exposure, and compares new tissue concentration data to threshold effects levels. Weak relationships between cadmium, mercury and selenium burdens and health biomarkers in common eider ducks (Somateria mollissima borealis) in Nunavut were found but it was concluded that metals were not influencing the health of these birds. Black guillemots (Cepphus grylle) examined near PCB-contaminated Saglek Bay, Labrador, had enlarged livers, elevated EROD and liver lipid levels and reduced retinol (vitamin A) and retinyl palmitate levels, which correlated to PCB levels in the birds. Circulating levels of thyroid hormones in polar bears (Ursus maritimus) were correlated to PCB and HO-PCB plasma concentrations, but the impact at the population level is unknown. High PCB and organochlorine pesticide concentrations were found to be strongly associated with impaired humoral and cell-mediated immune responses in polar bears, implying an increased infection risk that could impact the population. In beluga whale (Delphinapterus leucas), cytochromes P450 (phase I) and conjugating (phase II) enzymes have been extensively profiled (immunochemically and catalytically) in liver, demonstrating the importance of contaminants in relation to enzyme induction, metabolism and potential contaminant bioactivation and fate. Concentrations of OCs and metals in arctic terrestrial wildlife, fish and seabirds are generally below effects thresholds, with the possible exception of PCBs in burbot (Lota lota) in some Yukon lakes, Greenland shark (Somniosus microcephalus), glaucous and great black-backed gulls (Larus hyperboreus and L. marinus), and TEQs of dioxin-like chemicals in seabird eggs. PCB and DDT concentrations in several arctic marine mammal species exceed effects thresholds, although evidence of stress in these populations is lacking. There is little evidence that contaminants are having widespread effects on the health of Canadian arctic organisms, with the possible exception of polar bears. However, further research and better understanding of organohalogen exposure in arctic biota is needed considering factors such as tissue levels that exceed effects thresholds, exposure to "new" organohalogen contaminants of concern, contaminated regions, and climate change.


Fibrin clots in the choriocapillaris and serous detachment of the retina.
Clot formation occurs preferentially in the choriocapillaris. With intraocular inflammation this clotting begins along the inner surface of the choriocapillaris suggesting that dilatation of the vessels and opening of the endothelial fenestra have initiated the process. With the systemic coagulopathy of thrombotic thrombocytopenia (TTP) and disseminated intravascular coagulopathy (DIC) clotting occurs preferentially in the submacular choriocapillaris, sometimes associated with choroidal hemorrhage and detachment of the retina. These complications are illustrated in the present paper by a patient with TTP showing relatively chronic coagulopathy and by three patients with DIC showing variations of acute coagulopathy.


The epitope of monoclonal antibodies blocking erythrocyte invasion by Plasmodium falciparum map to the dimerization and receptor glycan binding sites of EBA-175.
The malaria parasite, Plasmodium falciparum, and related parasites use a variety of proteins with Duffy-Binding Like (DBL) domains to bind glycoproteins on the surface of host cells. Among these proteins, the 175 kDa erythrocyte binding antigen, EBA-175, specifically binds to glycophorin A on the surface of human erythrocytes during the process of merozoite invasion. The domain responsible for glycophorin A binding was identified as region II (RII) which contains two DBL domains, F1 and F2. The crystal structure of this region revealed a dimer that is presumed to represent the glycophorin A binding conformation as sialic acid binding sites and large cavities are observed at the dimer interface. The dimer interface is largely composed of two loops from within each monomer, identified as the F1 and F2 β-fingers that contact depressions in the opposing monomers in a similar manner. Previous studies have identified a panel of five monoclonal antibodies (mAbs) termed R215 to R218 and R256 that bind to RII and inhibit invasion of erythrocytes to varying extents. In this study, we predict the F2 β-finger region as the conformational epitope for mAbs, R215, R217, and R256, and confirm binding for the most effective blocking mAb R217 and R215 to a synthetic peptide mimic of the F2 β-finger. Localization of the epitope to the dimerization and glycan binding sites of EBA-175 RII and site-directed mutagenesis within the predicted epitope are consistent with R215 and R217 blocking erythrocyte invasion by Plasmodium falciparum by preventing formation of the EBA-175- glycophorin A complex.


Immune reactive proteins in patients irradiated for cervical cancer. One year follow up.
The parameters of nonspecific humoral immunity--serum immunoglobulins and immune complexes--were evaluated in irradiated group of patients with uterine cervix carcinoma (Stages IIB and IIIB), during one year follow up. The concentrations of IgA, which were elevated in patients before therapy, slowly declined after the radiotherapy, at the end of the follow up being returned to the normal range. The concentrations of IgG, which were significantly decreased in patients immediately after the therapy, were sharply and transiently elevated two months after the therapy; afterwards, the levels of IgG gradually decreased to the values which did not differ from their pre- or post-RT levels, as well as from control ones. The levels of CIC were not significantly changed after radiotherapy, although a transient increase was found seven months after radiotherapy, being not different from controls at the end of the follow up. The serum IgM remained in the range of control values immediately after radiotherapy, as well as during monitoring. The slow normalization of the serum IgA and CIC levels might reflect the success of the therapy.


A radiomics nomogram based on contrast-enhanced CT for preoperative prediction of Lymphovascular invasion in esophageal squamous cell carcinoma.
To develop a radiomics nomogram based on contrast-enhanced computed tomography (CECT) for preoperative prediction of lymphovascular invasion (LVI) status of esophageal squamous cell carcinoma (ESCC). The clinical and imaging data of 258 patients with ESCC who underwent surgical resection and were confirmed by pathology from June 2017 to December 2021 were retrospectively analyzed.The clinical imaging features and radiomic features were extracted from arterial-phase CECT. The least absolute shrinkage and selection operator (LASSO) regression model was used for radiomics feature selection and signature construction. Multivariate logistic regression analysis was used to develop a radiomics nomogram prediction model. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the performance and clinical effectiveness of the model in preoperative prediction of LVI status. We constructed a radiomics signature based on eight radiomics features after dimensionality reduction. In the training cohort, the area under the curve (AUC) of radiomics signature was 0.805 (95% CI: 0.740-0.860), and in the validation cohort it was 0.836 (95% CI: 0.735-0.911). There were four predictive factors that made up the individualized nomogram prediction model: radiomic signatures, TNRs, tumor lengths, and tumor thicknesses.The accuracy of the nomogram for LVI prediction in the training and validation cohorts was 0.790 and 0.768, respectively, the specificity was 0.800 and 0.618, and the sensitivity was 0.786 and 0.917, respectively. The Delong test results showed that the AUC value of the nomogram model was significantly higher than that of the clinical model and radiomics model in the training and validation cohort(P<0.05). DCA results showed that the radiomics nomogram model had higher overall benefits than the clinical model and the radiomics model. This study proposes a radiomics nomogram based on CECT radiomics signature and clinical image features, which is helpful for preoperative individualized prediction of LVI status in ESCC.


[Cystatin C and preclinical lesions in the target organs of hypertensive patients].
To study the association between cystatin C levels and preclinical lesions in the target organs (heart, kidney, vessels) of patients with hypertensive disease (HD) at moderate and high risks for cardiovascular events (CVE). The investigation enrolled 47 patents (30 men and 17 women) with Stages I-II HD at moderate (n = 23) and high (n = 24) risks for CVE. The patients' mean age was 46.0 ± 1.8 years; the duration of HD was 4.1 ± 0.2 years. The blood level of cystatin C was estimated by photometry using a biochemical autoanalyzer. Glomerular filtration rate (GFR) was calculated by the MDRD formula. Microalbuminuria (MAU) was determined by turbidimetry employing a biochemical autoanalyzer. No association between cystatin C level and 24-hour blood pressure (BP) monitoring readings was found in the patients except the men in whom it was correlated with 24-hour diastolic BP (DBP) (r = 0.36; p < 0.05). The hypertensive patients showed a positive correlation of cystatin C with their age (r = 0.51; p < 0.001). There were higher cystatin C levels in smoking patients with HD (n = 19) and no statistically significant differences in the level of MAU, urine uric acid, and GFR between them. There was a statistically highly significant negative. correlation between cystatin C concentration and GFR by the MDRD formula (r = -0.59; p < 0.001), at the same time, no correlation was found between creatinine clearance (by the Cockroft-Gault formula). There were no statistically significant differences in cystatin C levels in relation to the presence or absence of carotid atherosclerosis (1.01 ± 0.03 and 0.93 ± 0.02 mg/l, respectively; p = 0.08). Overall, there was a positive correlation of cystatin C levels with left ventricular mass index (r = 0.58; p < 0.001) and relative myocardial thickness index (r = 0.40; p < 0.05). The findings of the association of cystatin C and 24-hour DBP, preclinical lesions in the heart, vessels, and kidney seem to argue for the concept of cardiorenal syndrome in patients with HD just at its early stages.


Influence of Sociodemographic Factors in Measles-Rubella Campaign Compared with Routine Immunization at Mysore City.
Vaccines are mostly delivered through routine immunization and catch-up campaigns. Measles-rubella (MR) campaign, one of the largest vaccination campaigns, was launched on February 8, 2017, in five states of India including Karnataka. The objective of this study was to compare the association of various sociodemographic factors influencing routine immunization and MR campaign and to identify the reasons for nonvaccination. A cross-sectional study was done after the end of MR campaign, by interviewing parents of 147 children aged 9 months to 5 years in urban areas of Mysore. Sociodemographic factors and measles vaccination status by routine immunization and MR campaign were studied. The coverage of measles vaccination by routine immunization and the MR campaign was 93.9% (138/147) and 86.4% (127/147), respectively. While communication with field workers was significantly associated with both routine immunization and the MR campaign, religion and mother's educational status were associated with MR campaign (P < 0.05). The most common reason for not being vaccinated was lack of unawareness about the campaign and the location for vaccination which could have been curbed by health education. The study has shown that there are many factors which can be prevented by the health system that might help in improving immunization coverage.


GOOD VISUAL OUTCOME AT 1 YEAR IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION WITH PIGMENT EPITHELIUM DETACHMENT: Factors Influencing the Treatment Response.
To evaluate baseline and treatment factors influencing the response of pigment epithelial detachment (PED) in patients with treatment-naive neovascular age-related macular degeneration after 1 year of intravitreal anti-vascular endothelial growth factor treatment. This retrospective consecutive case series study included 104 eyes (94 patients) with treatment-naive neovascular age-related macular degeneration and associated PED >150 μm treated with aflibercept (n = 41) or ranibizumab (n = 63) for at least 1 year. Stepwise linear regression was used to assess factors influencing best-corrected visual acuity and PED response. At 1 year, the best-corrected visual acuity improved from 20/63 (60.8 ± 15.9 Early Treatment of Diabetic Retinopathy Study letters) at baseline to 20/40 (69.0 ± 15.0 letters) (P = 0.001), and PED maximal height decreased from 370.8 ± 205.6 μm to 238.8 ± 178.5 μm (P = 0.001). Multivariate analysis revealed an association of the visual improvement with lower best-corrected visual acuity at baseline (P = 0.001), the presence of foveal subretinal fluid (P = 0.001), and female gender (P = 0.047). Pigment epithelial detachment height reduction was dependent on higher baseline PED height (P = 0.001) and treatment drug (P = 0.008). Visual improvement in neovascular age-related macular degeneration with PED was equally achieved with ranibizumab and aflibercept, influenced mainly by baseline best-corrected visual acuity and foveal subretinal fluid. Pigment epithelial detachment height reduction was influenced by baseline height and the treatment drug, favoring aflibercept for a stronger effect. The clinical significance of this result warrants further studies.


Atypical MOG antibody disease presenting with typical multiple sclerosis lesions.
Myelin oligodendrocyte glycoprotein (MOG) antibody disease is an autoimmune disease of the central nervous system associated with a serological antibody against MOG, a glycoprotein expressed on the outer membrane of myelin. It is solely found within the central nervous system in the brain, optic nerves and spinal cord. MOG antibody disease falls within the neuromyelitis optica spectrum disorders (NMOSD), however clinical characteristics appear distinct from aquaporin-4 antibody related disease and multiple sclerosis. It has predilection for causing recurrent optic neuritis and transverse myelitis. Accurate diagnosis is important to determine long term prognosis and suitable treatment. We describe the case of a 42 year old woman previously labelled as MS who demonstrated a variable presentation of MOG antibody disease.


A Cross-Sectional Evaluation of Publication Bias in the Plastic Surgery Literature.
Publication bias (PB) is the preferential publishing of studies with statistically significant results. PB can skew findings of systematic reviews (SR) and meta-analyses (MA), with potential consequences for patient care and health policy. This study aims to determine the extent by which SRs and MAs in the plastic surgery literature evaluate and report PB. This cross-sectional study assessed PB reporting and analysis from plastic surgery studies published between January 1, 2015 and June 19, 2020. Full-texts of SRs and MAs were assessed by two reviewers for PB assessment methodology and analysis. Post-hoc assessment of studies that did not originally analyze PB was performed using Egger's regression, Duval and Tweedie's trim-and-fill, and Copas selection models. There were 549 studies evaluated, of which 531 full-texts were included. PB was discussed by 183 (34.5%) studies, and formally assessed by 97 (18.3%) studies. Among SR and MAs that formally assessed PB, PB was present in 24 (10.7%), not present in 52 (23.1%), and inconclusive in 8 (3.6%) studies; 141 (62.7%) studies did not report the results of their PB assessment. Funnel plots were the most common assessment method (n=88, 39.1%), and 60 (68.2%) studies published funnel plots. The post-hoc assessment revealed PB in 17/20 (85.0%) studies. PB is inadequately reported and analyzed amongst studies in the plastic surgery literature. Most studies that assessed PB found PB, as did post-hoc analysis of non-reporting studies. Increased assessment and reporting of PB amongst SRs and MAs would improve quality of evidence in plastic surgery.


Pathophysiology and clinical consequences of Raynaud's phenomenon related to systemic sclerosis.
According to the so-called vascular hypothesis, Raynaud's phenomenon (RP) is one initial event in the pathophysiological cascade leading to sclerosis in systemic sclerosis (SSc). It is characterized by recurrent, reversible spasms of small arterioles and digital arteries, usually triggered by cold and emotional stress. Clinical signs of RP are a sudden pallor of single digits of fingers followed by reactive hyperaemia and in severe cases also by cyanosis. Besides imbalances between vasoconstrictive and vasodilatory processes, structural alterations of the involved vessels are fundamental to secondary RP in SSc. The latter is the reason why secondary RP in SSc, in contrast to primary RP, often leads to ischaemia and re-perfusion injuries. New insights into the pathophysiology of RP feature a special role for alpha2c-adrenoreceptors, Rho-kinase signalling pathways and soluble mediators. They have resulted in promising therapeutic options, including antagonism of endothelin receptors, inhibition of phosphodiesterases or selective blockade of alpha2c-adrenoreceptors. They should also have a positive impact on the course of SSc in general.


Quantitative computer-aided diagnostic algorithm for automated detection of peak lesion attenuation in differentiating clear cell from papillary and chromophobe renal cell carcinoma, oncocytoma, and fat-poor angiomyolipoma on multiphasic multidetector computed tomography.
To evaluate the performance of a novel, quantitative computer-aided diagnostic (CAD) algorithm on four-phase multidetector computed tomography (MDCT) to detect peak lesion attenuation to enable differentiation of clear cell renal cell carcinoma (ccRCC) from chromophobe RCC (chRCC), papillary RCC (pRCC), oncocytoma, and fat-poor angiomyolipoma (fp-AML). We queried our clinical databases to obtain a cohort of histologically proven renal masses with preoperative MDCT with four phases [unenhanced (U), corticomedullary (CM), nephrographic (NP), and excretory (E)]. A whole lesion 3D contour was obtained in all four phases. The CAD algorithm determined a region of interest (ROI) of peak lesion attenuation within the 3D lesion contour. For comparison, a manual ROI was separately placed in the most enhancing portion of the lesion by visual inspection for a reference standard, and in uninvolved renal cortex. Relative lesion attenuation for both CAD and manual methods was obtained by normalizing the CAD peak lesion attenuation ROI (and the reference standard manually placed ROI) to uninvolved renal cortex with the formula [(peak lesion attenuation ROI - cortex ROI)/cortex ROI] × 100%. ROC analysis and area under the curve (AUC) were used to assess diagnostic performance. Bland-Altman analysis was used to compare peak ROI between CAD and manual method. The study cohort comprised 200 patients with 200 unique renal masses: 106 (53%) ccRCC, 32 (16%) oncocytomas, 18 (9%) chRCCs, 34 (17%) pRCCs, and 10 (5%) fp-AMLs. In the CM phase, CAD-derived ROI enabled characterization of ccRCC from chRCC, pRCC, oncocytoma, and fp-AML with AUCs of 0.850 (95% CI 0.732-0.968), 0.959 (95% CI 0.930-0.989), 0.792 (95% CI 0.716-0.869), and 0.825 (95% CI 0.703-0.948), respectively. On Bland-Altman analysis, there was excellent agreement of CAD and manual methods with mean differences between 14 and 26 HU in each phase. A novel, quantitative CAD algorithm enabled robust peak HU lesion detection and discrimination of ccRCC from other renal lesions with similar performance compared to the manual method.


Pro/con clinical debate: the use of a protected specimen brush in the diagnosis of ventilator associated pneumonia.
Although mechanical ventilation is instituted as a life-saving technique, it may lead to complications that can negatively impact on patients' morbidity and/or mortality. Ventilator associated pneumonia (VAP) is one such complication that is a common challenge to intensivists. Although most experts would agree that early 'appropriate' antibiotic use is essential in patients who develop VAP, the best diagnostic test to guide decision-making is far from clear. One diagnostic test that is capable of providing microbiological samples from the lower respiratory tree is invasive bronchoscopy with a protected specimen brush. Such a procedure has long been available to intensivists and is frequently employed in many intensive care units. However, this procedure has associated costs and potential complications, and its utility in VAP has been challenged. In this issue of Critical Care Forum, the two sides of this debate are brought forward with compelling arguments. The authors' arguments should fuel future trials.


Resveratrol Stimulates Hydrogen Sulfide (H2 S) Formation to Relax Murine Corpus Cavernosum.
Resveratrol (RVT) found in red wine protects against erectile dysfunction and relaxes penile tissue (corpus cavernosum) via a nitric oxide (NO) independent pathway. However, the mechanism remains to be elucidated. Hydrogen sulfide (H2 S) is a potent vasodilator and neuromodulator generated in corpus cavernosum. We investigated whether RVT caused the relaxation of mice corpus cavernosum (MCC) through H2 S. H2 S formation is measured by methylene blue assay and vascular reactivity experiments have been performed by DMT strip myograph in CD1 MCC strips. Endothelial NO synthase (eNOS) inhibitor Nω-Nitro-L-arginine (L-NNA, 0.1 mM) or H2 S inhibitor aminooxyacetic acid (AOAA, 2 mM) which inhibits both cystathionine-β-synthase (CBS) and cystathionine-gamma-lyase (CSE) enzyme or combination of AOAA with PAG (CSE inhibitor) has been used in the presence/absence of RVT (0.1 mM, 30 min) to elucidate the role of NO or H2 S pathways on the effects of RVT in MCC. Concentration-dependent relaxations to RVT, L-cysteine, sodium hydrogen sulfide (NaHS) and acetylcholine (ACh) were studied. Exposure of murine corpus cavernosum to RVT increased both basal and L-cysteine-stimulated H2 S formation. Both of these effects were reversed by AOAA but not by L-NNA. RVT caused concentration-dependent relaxation of MCC and that RVT-induced relaxation was significantly inhibited by AOAA or AOAA + PAG but not by L-NNA. L-cysteine caused concentration-dependent relaxations, which are inhibited by AOAA or AOAA + PAG significantly. Incubation of MCC with RVT significantly increased L-cysteine-induced relaxation, and this effect was inhibited by AOAA + PAG. However, RVT did not alter the effect of exogenous H2 S (NaHS) or ACh-induced relaxations. These results demonstrate that RVT-induced relaxation is at least partly dependent on H2 S formation and acts independent of eNOS pathway. In phosphodiesterase 5 inhibitor (PDE-5i) nonresponder population, combination therapy with RVT may reverse erectile dysfunction via stimulating endogenous H2 S formation.


Passive cutaneous anaphylaxis-inhibitory action of tectorigenin, a metabolite of tectoridin by intestinal microflora.
Tectoridin isolated from the flowers of Pueraria thunbergiana (Leguminosae) are metabolized to tectorigenin by human intestinal microflora. When tectoridin was orally administered to rats, tectorigenin, but not tectoridin, was detected in urine after beta-glucuronidase hydrolysis. The main metabolite tectorigenin potently inhibited the passive cutaneous anaphylaxis reaction and inhibited in vitro the release of beta-hexosaminidase from RBL-2H3 cells induced by IgE. These results suggest that tectoridin is a prodrug, which can be transformed into the active agent tectorigenin by human intestinal bacteria and can be a candidate for antiallergic agent.


Genome-wide responses to DNA-damaging agents.
Genome-wide studies of mRNA regulation and phenotypic responses have shown that eukaryotic cells mount a robust and multifaceted response upon exposure to DNA-damaging agents. The integration of theses studies over frameworks provided by protein-protein interactions, protein-DNA interactions, and subcellular localization information have led to the identification of networked responses to damage. Taken together, these studies illustrate that cellular protection from DNA and other macromolecular damage involves an intricate network of proteins involved in many different cellular functions, some of them expected (e.g., DNA repair and cell cycle checkpoints) but many of them unexpected (e.g., protein trafficking and degradation). This review highlights many of the studies that detail genome-wide responses to DNA-damaging agents and examines how these datasets have been used to build a systems view of cellular responses to damage.


Biological Activity of Polynesian Calophyllum inophyllum Oil Extract on Human Skin Cells.
Oil from the nuts of Calophyllum inophyllum, locally called "Tamanu oil" in French Polynesia, was traditionally used for wound healing and to cure various skin problems and ailments. The skin-active effect of "Tamanu oil emulsion" was investigated on human skin cells (keratinocytes and dermal fibroblasts) and showed cell proliferation, glycosaminoglycan and collagen production, and wound healing activity. Transcriptomic analysis of the treated cells revealed gene expression modulation including genes involved in the metabolic process implied in O-glycan biosynthesis, cell adhesion, and cell proliferation. The presence of neoflavonoids as bioactive constituents in Tamanu oil emulsion may contribute to these biological activities. Altogether, consistent data related to targeted histological and cellular functions brought new highlights on the mechanisms involved in these biological processes induced by Tamanu oil effects in skin cells.


COVID-19 meta-analyses: a scoping review and quality assessment.
To carry out a scoping review of the meta-analyses published regarding about coronavirus disease 2019 (COVID-19), evaluating their main characteristics, publication trends and methodological quality. A bibliometric search was performed in PubMed®, Scopus and Web of Science, focusing on meta-analyses about COVID-2019 disease. Bibliometric and descriptive data for the included articles were extracted and the methodological quality of the included meta-analyses was evaluated using A Measurement Tool to Assess Systematic Reviews. A total of 348 meta-analyses were considered eligible. The first meta-analysis about COVID-19 disease was published on February 26, 2020, and the number of meta-analyses has grown rapidly since then. Most of them were published in infectious disease and virology journals. The greatest number come from China, followed by the United States, Italy and the United Kingdom. On average, these meta-analyses included 23 studies and 15,200 participants. Overall quality was remarkably low, and only 8.9% of them could be considered as of high confidence level. Although well-designed meta-analyses about COVID-19 disease have already been published, the majority are of low quality. Thus, all stakeholders playing a role in COVID-19 deseases, including policy makers, researchers, publishers and journals, should prioritize well-designed meta-analyses, performed only when the background information seem suitable, and discouraging those of low quality or that use suboptimal methods.


[Primary aldosteronism--personal experience with diagnosis and surgical treatment of adenomatous forms].
Primary aldosteronism (Conn's syndrome) forms about 2% of disease in patients with arterial hypertension. Primary aldosteronism is in 50% of patients caused by aldosteron producing adenoma. Surgical treatment of these adenomas is excellent, or with complete disappearance of the disease, or with simple drug control of the symptoms after adrenalectomy. In the diagnostic process we can meet also seemingly divergent results of investigations. In these cases diagnosis usually requires the catheterization of adrenal veins with selected sampling of aldosteron level and thus determines the localisation of the tumor. Localised adenomas are indicated for surgical treatment. The best approach seems to be the abdominal transperitoneal incision with removal the whole adrenal gland. In this paper authors describe their experience with 5 patients treated at the F.D. Roosevelt Hospital in Banská Bystrica. (Tab. 1, Fig. 2, Ref. 25.)


Evaluation of Anesthesia Profile in Pediatric Patients after Inguinal Hernia Repair with Caudal Block or Local Wound Infiltration.
The aim of this study is to evaluate anesthesia and recovery profile in pediatric patients after inguinal hernia repair with caudal block or local wound infiltration. In this prospective interventional clinical study, the anesthesia and recovery profile was assessed in sixty pediatric patients undergoing inguinal hernia repair. Enrolled children were randomly assigned to either Group Caudal or Group Local infiltration. For caudal blocks, Caudal Group received 1 ml/kg of 0.25% bupivacaine; Local Infiltration Group received 0.2 ml/kg 0.25% bupivacaine. Investigator who was blinded to group allocation provided postoperative care and assessments. Postoperative pain was assessed. Motor functions and sedation were assessed as well. The two groups did not differ in terms of patient characteristic data and surgical profiles and there weren't any hemodynamic changes between groups. Regarding the difference between groups for analgesic requirement there were two major points - on one hand it was statistically significant p < 0.05 whereas on the other hand time to first analgesic administration was not statistically significant p = 0.40. There were significant differences in the incidence of adverse effects in caudal and local group including: vomiting, delirium and urinary retention. Between children undergoing inguinal hernia repair, local wound infiltration insures safety and satisfactory analgesia for surgery. Compared to caudal block it is not overwhelming. Caudal block provides longer analgesia, however complications are rather common.


Predictors of serum chromium levels after stainless steel posterior spinal instrumentation for adolescent idiopathic scoliosis.
Prospective cohort study. To determine the predictors of serum chromium levels after stainless steel posterior spinal instrumentation for adolescent idiopathic scoliosis. Abnormally elevated serum chromium levels have been detected in patients with adolescent idiopathic scoliosis after stainless steel instrumentation. To date, the relationship among serum chromium levels, time of implantation, and implant characteristics (including surface area, rod length, numbers of hooks, screws, and cross connectors) has not been studied. Thirty patients with adolescent idiopathic scoliosis undergoing posterior instrumented spinal arthrodesis using stainless steel implants between 1998 and 2002 were prospectively studied. Serum chromium levels were measured between October 2006 and June 2007. Postoperative radiographs were used to measure rod lengths, number of hooks, screws, cross-connectors, and cables. The surface area of each component and the total surface area for each patient were calculated. Possible associations between serum chromium levels, time of implantation, and implant characteristics were investigated. Implant exposure, whether expressed in the form of total metal implant surface area, rod length, or number of metal interfaces, was found to be positively associated with serum chromium levels. Specifically, chromium levels increased by a multiplicative factor of 1.0060 for every additional square centimeter of total metal implant surface area (P = 0.02). In addition, the chromium level was found to decrease by a multiplicative factor of 0.7766 for every additional year since surgery (P = 0.02). After adjusting for the number of years since surgery, metal implant exposure is positively associated with elevated serum chromium levels in adolescent idiopathic scoliosis patients with stainless steel posterior spinal implants. This is the first study to identify statistically significant positive associations between specific spinal implant characteristics (other than corrosion identified by radiographs) and serum chromium levels.


Exogenous Arachidonic Acid Affects Fucoxanthin Biosynthesis and Photoprotection in Phaeodactylum tricornutum.
Fucoxanthin is an oxygenated carotenoid component that has been reported to play important roles in anti-oxidation, anti-obesity and anti-cancer in the human body. Fucoxanthin-chlorophyll protein (FCP) complexes participate in light harvesting and photoprotection in diatom. In order to better understand the change of fucoxanthin content and its role in photoprotection, the growth, fucoxanthin biosynthesis and photosynthetic phenotypes were studied in the diatom Phaeodactylum tricornutum under the treatment of exogenous arachidonic acid (AA). Our results demonstrated that even low concentration of AA at 0.1 mg/L strongly induced fucoxanthin accumulation in algal cells to a maximum of 1.1 mg/g dry weight (DW), which was 36.6% higher than that in the untreated ones. By principal component analysis (PCA), we also identified a close correlation between fucoxanthin accumulation and the expression of genes involved in fucoxanthin biosynthesis, especially phytoene synthase (PSY), suggesting that AA change the metabolism of fucoxanthin by inducing carotenoid metabolic enzymes at the transcriptional level. Furthermore, we found that the exogenous application of AA affected non-photochemical quenching (NPQ) and photoinhibition, which resulted from the changed diadinoxanthin (DD) and diatoxanthin (DT) cycle, and thus played an important role in photoprotection.


DARC and D6: silent partners in chemokine regulation?
Chemokine receptors adorn the surface of leukocytes and other cell types ready to translate the extracellular chemokine environment into functional cellular outcomes. However, there are several molecules that, in many respects, look like chemokine receptors, but which do not have the ability to confer chemotactic potential to cell lines. This apparent silence spurred the search for signalling-independent functions and led to the development of new paradigms of chemokine regulation. In this review, we summarise the experimental basis for these ideas focussing on DARC and D6, the most studied members of this group of molecules. We discuss data generated using in vitro systems and genetically deficient mice, include results from observational human studies, and summarise the key findings of recent research. We take a critical look at current models of in vivo function highlighting important gaps in our knowledge and demonstrating that there is still much to find out about these enigmatic molecules.


Visually guided avoidance in the chameleon (Chamaeleo chameleon): response patterns and lateralization.
The common chameleon, Chamaeleo chameleon, is an arboreal lizard with highly independent, large-amplitude eye movements. In response to a moving threat, a chameleon on a perch responds with distinct avoidance movements that are expressed in its continuous positioning on the side of the perch distal to the threat. We analyzed body-exposure patterns during threat avoidance for evidence of lateralization, that is, asymmetry at the functional/behavioral levels. Chameleons were exposed to a threat approaching horizontally from the left or right, as they held onto a vertical pole that was either wider or narrower than the width of their head, providing, respectively, monocular or binocular viewing of the threat. We found two equal-sized sub-groups, each displaying lateralization of motor responses to a given direction of stimulus approach. Such an anti-symmetrical distribution of lateralization in a population may be indicative of situations in which organisms are regularly exposed to crucial stimuli from all spatial directions. This is because a bimodal distribution of responses to threat in a natural population will reduce the spatial advantage of predators.


Assessment outcome is weakly correlated with lecture attendance: influence of learning style and use of alternative materials.
The relation between lecture attendance and learning is surprisingly weak, and the role of learning styles in this is poorly understood. We hypothesized that 1) academic performance is related to lecture attendance and 2) learning style influences lecture attendance and, consequently, affects performance. We also speculated that the availability of alternative resources would affect this relationship. Second-year Bachelor of Science physiology students (n = 120) self-reported their lecture attendance in a block of 21 lectures (attendance not compulsory) and use of alternative resources. Overall self-reported lecture attendance was 73 ± 2%. Female students (n = 71) attended more lectures (16.4 ± 0.6) than male students (14.3 ± 0.08, n = 49) and achieved a higher composite mark in all assessments (73.6% vs. 69.3%, P < 0.02). Marks in the final exam were not statistically different between the sexes and correlated only weakly with lecture attendance (r = 0.29, n = 49, P < 0.04 for male students; r = 0.10, n = 71, P = not significant for female students; and r =0.21, n = 120, P < 0.02 for the whole class). Of the students who passed the exam, poor attenders (<11 lectures) reported significantly more use of lecture recordings (37 ± 8%, n = 15, vs. 10 ± 1%, n = 85, P < 0.001). In a VARK learning style assessment (where V is visual, A is auditory, R is reading/writing, and K is kinesthetic), students were multimodal, although female students had a slightly higher average percentage of the R learning style (preferred read/write) compared with male students (28.9 ± 0.9%, n = 63, vs. 25.3 ± 1.3%, n = 32, P < 0.03). Lecture attendance was not correlated with measured learning style. We concluded that lecture attendance is only weakly correlated with academic performance and is not related to learning style. The substitution of alternative materials for lecture attendance appears to have a greater role than learning style in determining academic outcomes.


[Ectopic ureter in pediatrics. A change in the way of presentation].
Classically, the diagnosis of ectopic ureter was done in grown up girls due to urinary incontinence, today the diagnoses are more precocious, which has partially changed treatment. The objective of this paper is to perform a review of our experience over the last years and to correlate it with the current type of presentation. We studied all patients with the diagnosis of ectopic ureter in a period of 10 years, between 1997 and December 2006. Demographic characteristics, type of presentation, diagnostic tests performed, age at the time of diagnosis and treatment were all analyzed, altogether with the different techniques employed for treatment. We found 19 patients with this disease, 15 of them females. Type of presentation was febrile urinary tract infection in 13 patients, urinary incontinence in two, and prenatal diagnosis of hydronephrosis in 4. Sixteen children had double pyeloureteral systems and only three had single systems. In all cases the diagnosis was performed with renal-bladder ultrasound, urethrocystogram and endoscopic studies. Additional studies such as excretion pyelograms were performed in 8 patients at the start of the series and nuclear medicine tests in 17. Median age at the time of diagnosis was eight months. All patients underwent surgical treatment. In patients with double systems superior heminephroureterectomy was performed in 8 patients, vesicoureteral reimplantation in three and pyelopyelic anastomosis in three cases with upper pole remnant function. In another two cases nephroureterectomy was performed due to the presence of reflux to the lower or system and severe renal compromise. In all three cases with single systems ureter reimplantation was performed. Currently prenatal suspicion and adequate study of urinary tract infections enable confirmation of ectopic ureter. Few children debut with urinary incontinence currently, due to the precocity of diagnosis. Treatment is always surgical, and basically depends on renal function, and the presence or absence of vesicoureteral reflux. Vesicoureteral reimplantation is performed preferentially in patients with ectopic ureter and a single system, and superior heminephrectomy in those with double systems, leaving the distal ureter of first option.


Global distribution of nearly identical phage-encoded DNA sequences.
Phages, the most abundant biological entities on the planet, play important roles in biogeochemical cycling, horizontal gene transfer, and defining microbial community composition. However, very little is known about phage diversity or biogeography, and there has not yet been a systematic effort to compare the phages found in different ecosystems. Here, we report that T7-like Podophage DNA polymerase sequences occur in every major biome investigated, including marine, freshwater, sediment, terrestrial, extreme, and metazoan-associated. The majority of these sequences belong to a unique clade that is only distantly related to cultured isolates. Some identical T7-like phage-encoded DNA polymerase genes from this clade were >99% conserved at the nucleotide level in multiple different environments, suggesting that these phages are moving between biomes in recent evolutionary time and that the global genomic pool for T7-like phages may be smaller than previously hypothesized.


Laparoscopic resection of an adrenal pseudocyst.
Adrenal pseudocysts are rare cystic lesions surrounded by a layer of fibrous tissue that lacks epithelial or endothelial cells. Patients with adrenal pseudocysts may be asymptomatic or present with abdominal pain or other gastrointestinal symptoms. We present the case of a morbidly obese 41- year-old woman who presented with left flank pain. A computed tomography scan of the abdomen and pelvis discovered an 8-cm adrenal lesion. The lesion was hormonally inactive and a transperitoneal laparoscopic left adrenalectomy was performed to exclude malignancy. Pathology discerned multiple pseudocysts with and without calcifications. The patient was discharged on postoperative day 2. She has been asymptomatic in terms of left flank pain for 12 months. We report this case in detail and briefly review the literature regarding adrenal pseudocysts.


Hydroxyl radical footprinting of DNA complexes of the ets domain of PU.1 and its comparison to the crystal structure.
Hydroxyl radical footprinting has been used to probe interactions in complexes between the ets domain of the murine transcription factor PU.1 and three different DNA restriction fragments, each containing one copy of the recognition sequence 5'-GGAA-3'. Two natural PU.1 binding sites, the SV40 enhancer site and the lambdaB motif of Ig lambda2-4 enhancer, were used as well as the PU.1 binding site present in the crystallized PU.1-DNA complex [Kodandapani, R., Pio, F., Ni, C.-Z., Piccialli, G., Klemsz, M., McKercher, S. R., Maki, R. A., and Ely, K. R. (1996) Nature 380, 456-460]. The footprints obtained for the three different DNA sequences are almost identical. The extent of contact with the protein was monitored for every base in the complex. Two concentration-dependent cleavage sites on the complementary TTCC strand are evidence of a specific interaction between PU.1 and the DNA. Two more protection sites and a hypersensitive cleavage site on the GGAA strand were observed. Although these data confirm the global structure of the PU.1-DNA complex as suggested by crystallography, the footprinting data reveal differences between the protein-DNA contacts in solution and in the crystal state. An additional interaction site not present in the crystal structure was observed by hydroxyl radical footprinting.


External validation of the cancer of the prostate risk assessment-s score in koreans undergoing radical prostatectomy.
To evaluate the validity of the University of California San Francisco Cancer of the Prostate Risk Assessment-S score (CAPRA-S score), a biochemical indicator of recurrent prostate cancer that uses histopathologic data, in Korean prostate cancer patients. A total of 203 prostate cancer patients who underwent radical prostatectomy between February 1997 and November 2010 were observed for longer than 6 months. The CAPRA-S score of 134 patients for whom records were available for preoperative prostate-specific antigen (PSA), pathologic specimen Gleason score, surgical margin, seminal vesicle invasion, extracapsular extension, and lymph node invasion were calculated. Biochemical recurrence was defined as repetitive measurement of PSA ≥0.2 ng/mL at least 6 months after surgery with at least a 4-week interval. The Cox proportional hazard model and Kaplan-Meier analysis were used for the statistical testing. The CAPRA-S scores were divided into nine groups. The 5-year disease-free survival rate was reduced as the CAPRA-S score increased compared with the group with a CAPRA-S score of 0-1. The CAPRA-S score in this study was more sensitive to biochemical recurrence than was the CAPRA score conducted at this institution (CAPRA-S concordance index, 0.776; CAPRA concordance index, 0.728). The CAPRA-S score is judged to be a useful tool for predicting the disease-free survival rate of Korean prostate cancer patients and is thought to assist in establishing postoperative management.


Influence of ginseng on mating behavior of male rats.
Experiment on the mating behavior of male albino rats paired with receptive females established that in comparison with control animals, males under the influence of ginseng (a) began ejaculation earlier and repeated the action more often in a 45-minute observation period and (b) deposited more copulation plugs in 10 days. The data suggest that ginseng facilitates the mating behavior of male rats.


Vanadium-based nanowires for sodium-ion batteries.
Sodium-ion batteries (SIBs) have received great attention because of the abundance source and low cost. To date, some Na+ storage materials have achieved great performance, but the larger Na+ radius and more complex Na+ storage mechanism compared with Li+ still limit the energy density and power density. This review systematically summarizes emerging synthetic technologies of vanadium-based materials from simple nanowires to complicated modified/optimized structures. In addition, vanadium-based nanowire materials are reviewed at both the cathode and anode side, and advantages and drawbacks are proposed to explain the challenges facing application of novel materials. Furthermore, a vanadium-based single-nanowire device is reported to reveal the Na+ storage mechanism, which contributes to the understanding of the reaction in SIBs. Finally, this review summarizes the current development challenges of SIBs and looks forward to the future development prospects of vanadium-based nanowires, providing a new direction for further applications of SIBs.


Graphene oxide-based substrate: physical and surface characterization, cytocompatibility and differentiation potential of dental pulp stem cells.
The aim of this study was to evaluate the cytotoxicity and differentiation potential of a graphene oxide (GO)-based substrate using dental pulp stem cell (DPSC). GO was obtained via chemical exfoliation of graphite using the modified Hummer's method and dispersed in water-methanol solution. 250μL of 1.5mg/mL solution were added to a cover slip and allowed to dry (25°C, 24h). GO-based substrate was characterized by Raman spectroscopy, AFM and contact angle. DPSC were seeded on GO and glass (control). Cell attachment and proliferation were evaluated by polymeric F-actin staining, SEM and MTS assay for five days. mRNA expression of MSX-1, PAX-9, RUNX2, COL I, DMP-1 and DSPP were evaluated by qPCR (7 and 14 days). Statistical analyses were performed by either Mann-Whitney, one or two-way Anova followed by and Tukey's post hoc analysis (α=0.05). Peaks at 1587cm(-1) and 1340cm(-1) (G and D band) and ID/IG of 0.83 were observed for GO with Raman. AFM showed that GO was randomly deposited and created a rougher surface comparing to the control. Cells successfully adhered on both substrates. There was no difference in cell proliferation after 5 days. Cells on GO presented higher expression for all genes tested except MSX-1 and RUNX2 for 7 days. GO-based substrate allowed DPSC attachment, proliferation and increased the expression of several genes that are upregulated in mineral-producing cells. These findings open opportunities to the use of GO alone or in combination with dental materials to improve their bioactivity and beyond.


Microbial Rhodopsins: Diversity, Mechanisms, and Optogenetic Applications.
Microbial rhodopsins are a family of photoactive retinylidene proteins widespread throughout the microbial world. They are notable for their diversity of function, using variations of a shared seven-transmembrane helix design and similar photochemical reactions to carry out distinctly different light-driven energy and sensory transduction processes. Their study has contributed to our understanding of how evolution modifies protein scaffolds to create new protein chemistry, and their use as tools to control membrane potential with light is fundamental to optogenetics for research and clinical applications. We review the currently known functions and present more in-depth assessment of three functionally and structurally distinct types discovered over the past two years: (a) anion channelrhodopsins (ACRs) from cryptophyte algae, which enable efficient optogenetic neural suppression; (b) cryptophyte cation channelrhodopsins (CCRs), structurally distinct from the green algae CCRs used extensively for neural activation and from cryptophyte ACRs; and


Angiographic patterns of restenosis after drug-coated balloon angioplasty for femoropopliteal lesions and 1-year prognosis after repeat endovascular therapy.
The aim of the current study sought to investigate the angiographic patterns of restenosis after drug-coated balloon (DCB) angioplasty for femoropopliteal (FP) lesions and which repeat endovascular therapy (EVT) for DCB restenosis would provide more freedom from recurrent restenosis. This retrospective multicenter study included 119 limbs (chronic limb-threatening ischemia [CLTI]: 55%, lesion length: 136.9 ± 89.6 mm, chronic total occlusion: 25%) of 95 patients (diabetes mellitus: 70%, hemodialysis: 56%) who were diagnosed with DCB restenosis between January 2018 and December 2019. The cases were classified into three groups based on angiographic patterns of restenosis: Class I: focal lesions ≤50 mm, Class II: diffuse lesions >50 mm, and Class III: totally occluded lesions. The DCB restenosis patterns and frequency and predictors of recurrent restenosis after repeated EVT (re-EVT) were investigated. The mean follow-up duration was 29.8 ± 9.5 months. Groups I, II, and III comprised of 30 (25.2%), 55 (46.2%), and 34 (29.0%) cases, respectively. The overall rate of 1-year freedom from recurrent restenosis was 58.2%. One-year rate of freedom from recurrent restenosis after repeat DCB was not statistically different from that after scaffolding (71.1% vs. 74.6%, respectively, p = 0.911); however, it was significantly better than that after noncoated balloon angioplasty (repeat DCB vs. noncoated balloon angioplasty: 71.1% vs. 25.7%, respectively, p < 0.001). Multivariate analysis demonstrated that CLTI (hazard ratio [HR]: 5.15, p < 0.001) and re-EVT with noncoated balloon (HR: 3.16, p < 0.001) were significantly associated with recurrent restenosis; however, Class III pattern of DCB restenosis was not associated with recurrent restenosis (HR: 1.04, p = 0.918). This study revealed the angiographic patterns of restenosis after DCB therapy for FP lesions and the 1-year rate of recurrent restenosis after repeat revascularization. Repeat DCB therapy demonstrated acceptable 1-year recurrent restenosis rates.


Associations of fat and muscle mass with overall survival in men with prostate cancer: a systematic review with meta-analysis.
To systematically review and analyse the associations between fat and muscle mass measures with overall survival in men with prostate cancer. A systematic search was conducted in CINAHL, Cochrane Library, EMBASE, PubMed, and Web of Science databases from inception to December 2020, while abstracts from the American Society of Clinical Oncology (ASCO), Clinical Oncology Society of Australia (COSA), and the American College of Sports Medicine (ACSM) conferences were searched from 2014 to 2020. Eligible articles examined the association of body composition measures, such as fat mass (e.g., fat mass, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT) and muscle mass measures, with overall survival in prostate cancer patients at any treatment stage. The primary endpoint was overall survival. Random-effect meta-analysis was conducted for studies reporting multivariable or univariable analysis assessing the associations of fat mass measures (i.e., fat mass, VAT, SAT, VAT/SAT) and muscle mass measures with overall survival. Sixteen cohort studies that comprised 4807 men with prostate cancer were included. Total adiposity (hazard ratio (HR) 0.98, 95% CI: 0.75-1.28, p = 0.888) and VAT (HR 1.03, 95% CI: 0.74-1.43, p = 0.873) were not significantly associated with overall survival, while higher subcutaneous adipose tissue levels were associated with higher survival (HR 0.68, 95% CI: 0.54-0.84, p = 0.001). Greater mortality risk was found in patients with localised (HR 1.91, 95% CI: 1.40-2.62, p < 0.001) and advanced disease (HR 1.43, 95% CI: 1.07-1.92, p = 0.020) presenting with low levels of muscle mass compared to those presenting with high levels. These results indicate that although overall adiposity should be cautiously interpreted in regards to survival, high muscle mass and SAT, and low VAT/SAT ratio values are associated with overall survival in men with prostate cancer.


Successful Shrinkage of a Giant Cutaneous Squamous Cell Carcinoma with Immunotherapy in a Kidney Transplant Recipient.
A 56-year-old male living donor kidney transplant recipient presented with a giant cutaneous squamous cell carcinoma in his right parotid region. Programmed radiotherapy had been previously terminated due to lesion ulceration and bleeding. He was characterized as a terminal case. We applied cemiplimab, which is an immune checkpoint inhibitor against the pro-grammed cell death receptor PD-1. After 6 months, the cutaneous squamous cell carcinoma had shrunk and had stopped bleeding. The patient was treated with methylprednisolone, cyclosporine, and mycophenolate mofetil during this period. He had 2 rejection episodes defined as doubling baseline serum creatinine with no other explanation. Both episodes were successfully treated with intravenous methylprednisolone, while immunotherapy was postponed for 10 days. In both cases, serum creatinine returned to baseline within 1 week. Immune checkpoint inhibitors are indicated for invasive cutaneous squamous cell carcinoma therapy, and the risk of acute rejection should not prevent the use of these agents in kidney transplant recipients, because immune checkpoint inhibitors may enhance the quantity and quality of life of such patients.


Analysis of redox states of protic and aprotic solutions irradiated by low linear energy transfer carbon-ion beams using a 2,2-diphenyl-1-picrylhydrazyl radical.
The quantitative evaluation of changes in the redox state induced by low linear energy transfer (LET) radiations such as the plateau region of heavy-ion beams via formation of reactive oxygen species is of considerable importance to eliminate the adverse effects of radiation therapy on normal tissues adjacent to a tumour. In this study, a 2,2-diphenyl-1-picrylhydrazyl radical (DPPH˙) was used as a redox probe to estimate the redox states of protic and aprotic solutions irradiated by low LET carbon-ion (C-ion) beams. The dose dependence of the decrease in the absorption band due to DPPH˙ (which was solubilised by β-cyclodextrin (β-CD) in water) after irradiation with low LET C-ion beams (13 keV μm-1) was similar to that after X-irradiation. Similar results were obtained when H2O was replaced with methanol or acetonitrile although the slope values of the plots of the absorbance changes vs. radiation doses were twice larger as compared to the case in β-CD-containing H2O. Moreover, DPPH˙ was more susceptible to the C-ion beam than to X-rays in isopropyl myristate (IPM), which is one of the saturated fatty acid esters.


Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices.
The aim of this study was to compare the performance of fecal lactoferrin (Lf), calprotectin (Cal), polymorphonuclear neutrophil elastase (PMN-e), as well as serum C-reactive protein (CRP) in patients with inflammatory bowel diseases (IBD) to address (a) whether these markers can differentiate IBD patients with endoscopically assessed inflammation from IBD patients without inflammation and from irritable bowel syndrome (IBS); (b) whether they correlate with endoscopic severity of inflammation; and (c) whether a combination of fecal markers with the respective disease-specific activity indices may increase the diagnostic accuracy with reference to the endoscopic severity of inflammation. Fecal levels of Lf, Cal, and PMN-e and serum CRP were assessed in 139 patients undergoing diagnostic ileocolonoscopy (54 IBS patients, 42 ulcerative colitis [UC], 43 Crohn's disease [CD]). Disease activity was determined for CU with the colitis activity index (CAI) and for CD with the Crohn's disease activity index (CDAI). The performance of each marker with reference to endoscopic inflammatory activity was assessed by computing correlations, and sensitivity and specificity using published as well as adjusted cutoffs. A comprehensive activity index was computed by combining results from fecal markers, serum CRP, and a clinical activity index. UC or CD patients with active inflammation demonstrated significantly higher levels of Lf, Cal, and PMN-e in feces as well as serum-CRP when compared to patients with inactive inflammation as well as patients with IBS (all P < 0.05). Using adjusted cutoffs enabled a marked improvement of all markers with an overall diagnostic accuracy in IBD of 80.0% for Lf, 80.0% for Cal, 74.1% for PMN-e, 64.0% for CRP, and 79.0% for the respective clinical disease scores. Cal showed the highest diagnostic accuracy in CD (81.4%), whereas Lf was superior to the other markers in UC (83.3%). The comprehensive activity index yielded a further improvement of sensitivity and specificity, with a diagnostic accuracy of 95.3% for UC patients. The fecal markers Lf, Cal, and PMN-e are able to differentiate active IBD from inactive IBD as well as from IBS. None of these three stool markers is consistently superior in its ability to reflect endoscopic inflammation, but all three are superior to CRP in their diagnostic accuracy. A combination of the stool markers with the CRP and a disease-specific activity index in a categorical comprehensive activity index can increase the diagnostic accuracy with reference to the endoscopic inflammation in UC.


Carcinosarcoma of the rectosigmoid colon in a 13-year-old girl.
Reported herein is an unusual case of carcinosarcoma of the colon. A 13-year-old girl was transferred to Chonbuk National University Hospital, Korea with a known pelvic mass. CT and magnetic resonance imaging confirmed a large pelvic mass. A sarcoma was diagnosed following colonoscopic biopsy. An ultra-low anterior resection with pelvic lymph node dissection was performed. The tumor consisted of a well-differentiated adenocarcinoma showing strong immunoreactivity to epithelial markers (pancytokeratin, cytokeratin 7, cytokeratin 19, cytokeratin 20, epithelial membrane antigen, and CEA) and a sarcomatous lesion with strong diffuse vimentin expression but no immunoreactivity to any of the six epithelial markers. Carcinosarcomas of the colon are extremely rare, and all reported cases involve adults. To the authors' knowledge, this is the first reported case of a carcinosarcoma of the colon in a child.


Subcutaneous pleomorphic adenomas in two different areas of the face.
A 41-year-old woman developed two subcutaneous pleomorphic adenomas on her face. Pleomorphic adenoma usually arises as a benign tumour of a major salivary gland and often develops multifocally within the gland. These two pleomorphic adenomas originated in the subcutaneous layer of the face, also multifocally. They were excised, she made a good recovery, and she had no signs of recurrence a year later.


Treatment and follow-up variables discriminating abstainers, controlled drinkers and relapsers.
A group of behaviorally treated abstainers, controlled drinkers and relapsers who had been followed up for a minimum of 1 year were compared on eight treatment and 11 posttreatment variables. Discriminating characteristics of abstainers were their goal of abstinence at discharge and length of attendance at aftercare facilities. Controlled drinkers had a goal of controlled drinking and were most likely to have had controlled drinking training during treatment. Relapsers were most likely to have been discharged from treatment prematurely, to receive further treatment and to use psychotropic medication. No controlled drinkers attended Alcoholics Anonymous or received residential care during follow-up in contrast to a small proportion of abstainers and relapsers who did. Some aspects of the drinking behavior of controlled drinkers and relapsers were also studied. Controlled drinkers were more likely to have a period of initial abstinence and for a longer period of time. Of the controlled drinkers, 66% drank at least once per week and 86% set themselves drinking limits; average consumption of alcohol was 48 and 32 g/day by men and women, respectively. The majority of controlled drinkers changed their preferred beverage and their social and physical drinking environment after treatment in accordance with therapeutic advice.


Spatial Configuration of Drought Disturbance and Forest Gap Creation across Environmental Gradients.
Climate change is increasing the risk of drought to forested ecosystems. Although drought impacts are often anecdotally noted to occur in discrete patches of high canopy mortality, the landscape effects of drought disturbances have received virtually no study. This study characterized the landscape configuration of drought impact patches and investigated the relationships between patch characteristics, as indicators of drought impact intensity, and environmental gradients related to water availability to determine factors influencing drought vulnerability. Drought impact patches were delineated from aerial surveys following an extreme drought in 2011 in southwestern Australia, which led to patchy canopy dieback of the Northern Jarrah Forest, a Mediterranean forest ecosystem. On average, forest gaps produced by drought-induced dieback were moderate in size (6.6 ± 9.7 ha, max = 85.7 ha), compact in shape, and relatively isolated from each other at the scale of several kilometers. However, there was considerable spatial variation in the size, shape, and clustering of forest gaps. Drought impact patches were larger and more densely clustered in xeric areas, with significant relationships observed with topographic wetness index, meteorological variables, and stand height. Drought impact patch clustering was more strongly associated with the environmental factors assessed (R2 = 0.32) than was patch size (R2 = 0.21); variation in patch shape remained largely unexplained (R2 = 0.02). There is evidence that the xeric areas with more intense drought impacts are 'chronic disturbance patches' susceptible to recurrent drought disturbance. The spatial configuration of drought disturbances is likely to influence ecological processes including forest recovery and interacting disturbances such as fire. Regime shifts to an alternate, non-forested ecosystem may occur preferentially in areas with large or clustered drought impact patches. Improved understanding of drought impacts and their patterning in space and time will expand our knowledge of forest ecosystems and landscape processes, informing management of these dynamic systems in an uncertain future.


[An unexpected delivery in Mayotte].
The particular social-cultural context of Mayotte is resulting in an increase in the number of unexpected home births. When a secondary emergency response vehicle is dispatched, A & E nurses are involved in providing prehospital care, sometimes in difficult conditions, as one nurse testifies in this account.


Steroid levels and steroid metabolism in relation to early gonadal development in the tilapia Oreochromis niloticus (Teleostei: cyprinoidei).
Sex steroid levels and steroid metabolism were investigated in relation to early gonadal development in a mixed sex population of the tilapia Oreochromis niloticus. Androstenedione (AD), testosterone (T), 11-ketotestosterone (KT), and estradiol (E2) were quantified by radioimmunoassay (RIA) of whole body extracts. Androstenedione metabolism was assessed by incubations in vitro with 3H-AD and metabolites were identified by thin-layer chromatography coupled with radioisotope image analysis. Histology revealed the presence of gonadal structures at 15 days postfertilization (dpf) and ovaries at 36 dpf, with other individuals exhibiting undifferentiated gonads containing germinal cells, presumably eventual testes. Androgen levels were initially high in eggs then decreased severalfold prior to the emergence of gonads. A transient increase in the levels of T and KT occurred at 22 dpf. Levels of E2 were either low or undetectable except for a transient increase (43 dpf) after ovaries were present. Levels of T approached bimodality from 57 to 64 dpf. Steroid metabolism generally increased throughout development. Metabolites were generally similar, consisting of T predominantly as well as 5beta-reduced androgen derivatives and 11-oyxgenated derivatives. Estriol was tentatively identified. Conjugated steroids were not formed. Two types of steroid metabolic profiles occurred at 50 dpf. These results demonstrate that changes in the steroidogenic profile occur during early transitions of gonadal development. Notably, (1) steroid biosynthetic capacity preceeds gonadal differentiation, (2) evidence for estrogens occurs after ovarian development has begun, and (3) bimodality of levels of T and differential steroid metabolism later in development may reflect the onset of sexual divergence.


Disseminating research to different audiences: lessons learned from the UNICEF Innocenti Report Card Project.
As the academic world becomes increasingly aware of the need to improve the dissemination of research, this article considers some of the theoretical issues involved in the communication of research to non-specialist audiences. It also demonstrates how theory can be put into practice using the case study of a UNICEF Innocenti Report Card on childhood injury.


Magnetic-field-limited currents.
An upper limit on the net current of a charged particle beam is derived by requiring the energy per unit length in the magnetic field to be less than that in the particles. The limit is calculated for five different current profiles. It is shown that an arbitrarily large net current can propagate in a large diameter ring. The results are found to be closely related to the Alfvén limit. A limit on the forward current in a conductor is calculated, which defines a magnetic inhibition time.


Intracellular electrophysiological alterations in canine cardiac conducting tissue induced by aprindine and lignocaine.
The effects of aprindine and lignocaine (lidocaine USP) were compared on intracellularly recorded potentials from normal canine conducting tisues. Only aprindine produced marked depression of the maximum rate of rise (Vmax) of action potentials elicited at normal cycle lengths (1000 ms). Both compounds, however, produced enhanced depression of Vmax at short cycle lengths or at short S1-S2 coupling intervals at normal membrane resting potential. Both lignocaine and aprindine shorten the action potential duration (APD) and effective refractory period (ERP) but increase the EPR/APD ratio. These effects are easily reversible upon perfusion with drug-free solution only in the case of lignocaine.