Risk of dementia in peritoneal dialysis patients compared with hemodialysis patients.
Compared with similarly aged controls, patients with end-stage renal disease (ESRD) have a higher prevalence of cognitive impairment and more rapid cognitive decline, which is not explained by traditional risk factors alone. Since previous small studies suggest an association of cognitive impairment with dialysis modality, we compared incident dementia among patients initiating hemodialysis (HD) vs peritoneal dialysis (PD) in a large national cohort. This is a retrospective cohort study of incident dialysis patients in the United States from 2006 to 2008 with no diagnosis of dementia prior to beginning dialysis. We evaluated the effect of initial dialysis modality on incidence of dementia, diagnosed by Medicare claims data, adjusted for baseline demographic and clinical data from the USRDS registry. Our analysis included 121,623 patients, of whom 8,663 initiated dialysis on PD. The mean age of our cohort was 69.2 years. Patients who initiated PD had a lower cumulative incidence of dementia than those who initiated HD (1.0% vs 2.7%, 2.5% vs 5.3%, and 3.9% vs 7.3% at 1, 2, and 3 years, respectively). The risk of dementia for patients who started on PD was lower compared with those who started on HD, with a hazard ratio (HR) = 0.46 [0.41, 0.53], in an unadjusted model and HR 0.74 [0.64, 0.86] in a matched model. Dialysis modality is associated with incident dementia in a cohort of older ESRD patients. This finding warrants further investigation of the effect of dialysis modality on cognitive function and evaluation for possible mechanisms.


Molecularly Imprinted Synthetic Antibodies: From Chemical Design to Biomedical Applications.
Billions of dollars are invested into the monoclonal antibody market every year to meet the increasing demand in clinical diagnosis and therapy. However, natural antibodies still suffer from poor stability and high cost, as well as ethical issues in animal experiments. Thus, developing antibody substitutes or mimics is a long-term goal for scientists. The molecular imprinting technique presents one of the most promising strategies for antibody mimicking. The molecularly imprinted polymers (MIPs) are also called "molecularly imprinted synthetic antibodies" (MISAs). The breakthroughs of key technologies and innovations in chemistry and material science in the last decades have led to the rapid development of MISAs, and their molecular affinity has become comparable to that of natural antibodies. Currently, MISAs are undergoing a revolutionary transformation of their applications, from initial adsorption and separation to the rising fields of biomedicine. Herein, the fundamental chemical design of MISAs is examined, and then current progress in biomedical applications is the focus. Meanwhile, the potential of MISAs as qualified substitutes or even to transcend the performance of natural antibodies is discussed from the perspective of frontier needs in biomedicines, to facilitate the rapid development of synthetic artificial antibodies.


Development of the RIKEN database for dynamic facial expressions with multiple angles.
The development of facial expressions with sensing information is progressing in multidisciplinary fields, such as psychology, affective computing, and cognitive science. Previous facial datasets have not simultaneously dealt with multiple theoretical views of emotion, individualized context, or multi-angle/depth information. We developed a new facial database (RIKEN facial expression database) that includes multiple theoretical views of emotions and expressers' individualized events with multi-angle and depth information. The RIKEN facial expression database contains recordings of 48 Japanese participants captured using ten Kinect cameras at 25 events. This study identified several valence-related facial patterns and found them consistent with previous research investigating the coherence between facial movements and internal states. This database represents an advancement in developing a new sensing system, conducting psychological experiments, and understanding the complexity of emotional events.


[Microcalorimetric study of the domain organization of serum albumin].
Scanning microcalorimetry was used for studying the melting of the structure of human and bovine serum albumins and their fragments. It was shown that the melting of the native structure of serum albumin observed by the excessive heat absorption is a complex process which is described by three simple transitions overlapping in temperature. This means that the serum albumin molecule consists of three more or less independent cooperative structures, domains.


Reiter's syndrome and recurrent peritonitis after appendectomy.
A 15-year-old male adolescent underwent an appendectomy for acute gangrenous appendicitis. One week after surgery, he underwent an exploratory laparotomy that revealed two pericecal abscesses, which were drained. Two weeks later, he had diffuse peritonitis and underwent another laparotomy, which revealed a sterile fibrinous peritonitis. Oligoarticular inflammatory arthritis, urethritis, and recurrent peritonitis subsequently developed. He was found to be positive for HLA-B27 antigens. This case report illustrates that reactive arthritis (Reiter's syndrome) may develop after peritoneal infections. It also raises the possibility that the inflammatory process, which involves other serosal surfaces in Reiter's syndrome, may affect the peritoneum.


Impact of optimal follow-up of monoclonal gammopathy of undetermined significance on early diagnosis and prevention of myeloma-related complications.
Monoclonal gammopathy of undetermined significance (MGUS) is associated with a long-term risk of progression to multiple myeloma (MM) or related malignancy. To prevent serious myeloma-related complications, lifelong annual follow-up has been recommended, but its value is unknown. We reviewed all patients from southeastern Minnesota seen at Mayo Clinic between 1973 and 2004 with MGUS who subsequently progressed to MM. Of 116 patients, 69% had optimal follow-up of MGUS. Among these, abnormalities on serial follow-up laboratory testing led to the diagnosis of MM in 16%, whereas MM was diagnosed only after serious MM-related complications in 45%. In the remaining, workup of less serious symptoms (25%), incidental finding during workup of unrelated medical conditions (11%), and unknown (3%) were the mechanisms leading to MM diagnosis. High-risk MGUS patients (≥ 1.5 g/dL and/or non-IgG MGUS) were more likely to be optimally followed (81% vs 64%), and be diagnosed with MM secondary to serial follow-up testing (21% vs 7%). This retrospective study suggests that routine annual follow-up of MGUS may not be required in low-risk MGUS. Future studies are needed to replicate and expand our findings and to determine the optimal frequency of monitoring in higher-risk MGUS patients.


[Surgical treatment of syphilitic ascending aortic aneurysm: a case report].
A 67-year-old man with positive serum reaction for syphilis had been followed by cardiologist for his moderate-sized saccular ascending aortic aneurysm and small-sized abdominal aortic aneurysm. Because of his transient ischemic attack probably secondary to the thrombo-embolism of the aneurysm and rapid growing of its size, surgical treatment was recommended. Resection of the saccular aneurysm with patch plasty of the ascending aorta was performed under the cardiopulmonary bypass associated with right side cerebral perfusion. At the time of operation, the mildly dilated ascending aorta and arch with multiple intimal ulceration were noted. Although his postoperative hemodynamic condition was stable, he suffered from multiple cerebral infarction, probably due to embolism migrated from the fragile aortic intima. His neurological condition was improved promptly, trivial hemi-paralysis was remained. The specimen of resected aneurysmal wall revealed syphilitic changes microscopically. We concluded that the extent of the aortic replacement with prosthetic graft should be deceived not only with its external appearance, but also with the changes of its inside.


[Electrophysiological aspects of the indicators of hemispheric asymmetry during reparative processes in the brain after unilateral lesions].
The gears of the conjugate activity of hemispheres in the presence of damage in one were studied before and after removal of a tumor by using an interhemispheric asymmetry index. On left hemispheric exposure, the index decreased in the anterior brain regions having mainly morphofunctional connections with the activating structures of the stem. The posterior cortical regions changed the index on exposures of the right hemisphere or synchronizing stem structures. In an operated-on patients, the damaging action at any site reduced the index in the anterior cortical regions. Interhemispheric asymmetry of the posterior regions increased or unchanged with left hemispheric damage and decreased with right hemispheric one. These changes are interpreted as a reflection of compensatory rearrangements of interhemispheric interactions which are accomplished under the influence of the activating and synchronizing systems of the brain stem.


The Association of Lesion Location and Sleep Related Breathing Disorder in Patients with Acute Ischemic Stroke.
Sleep related breathing disorders (SRBD) are common in patients with ischemic stroke and are associated with poor outcome. SRBD after stroke were assumed to be a direct consequence of injury of specific central nervous system structures. However, whether specific locations of ischemic infarcts cause SRBD is yet unknown. We therefore investigated the association of ischemic lesion location with SRBD. Patients with acute ischemic stroke treated on our stroke unit were included in a prospective observational study. All patients underwent magnetic resonance imaging (MRI) and polygraphy in the acute phase after stroke. SRBD was defined by an apnea-hypopnea index (AHI) ≥10. MRI were evaluated using standardized maps to depict voxel-wise probability distribution of infarction for patients with and without SRBD. Groups were compared using logistic regression analysis. Of 142 patients included, 86 (59%) had a SRBD. Age, body mass index and prevalence of arterial hypertension were significantly higher in patients with SRBD. There was no statistically significant association between any lesion location and SRBD. We found no association of lesion location and SRBD in stroke patients, whereas established risk factors for SRBD, known from general population, were significantly associated with SRBD. Given the high prevalence of SRBD in stroke patients, these findings suggest that cerebral ischemia facilitates the occurrence of SRBD in patients with pre-existing risk factors rather than causing it by damaging specific central nervous system structures. Our findings can be used to identify stroke patients who might benefit from polygraphy screening.


Are osseous artefacts a window to perishable material culture? Implications of an unusually complex bone tool from the Late Pleistocene of East Timor.
We report the discovery of an unusually complex and regionally unique bone artefact in a Late Pleistocene archaeological assemblage (c. 35 ka [thousands of years ago]) from the site of Matja Kuru 2 on the island of Timor, in Wallacea. The artefact is interpreted as the broken butt of a formerly hafted projectile point, and it preserves evidence of a complex hafting mechanism including insertion into a shaped or split shaft, a complex pattern of binding including lateral stabilization of the cordage within a bilateral series of notches, and the application of mastic at several stages in the hafting process. The artefact provides the earliest direct evidence for the use of this combination of hafting technologies in the wider region of Southeast Asia, Wallacea, Melanesia and Australasia, and is morphologically unparallelled in deposits of any age. By contrast, it bears a close morphological resemblance to certain bone artefacts from the Middle Stone Age of Africa and South Asia. Examination of ethnographic projectile technology from the region of Melanesia and Australasia shows that all of the technological elements observed in the Matja Kuru 2 artefact were in use historically in the region, including the unusual feature of bilateral notching to stabilize a hafted point. This artefact challenges the notion that complex bone-working and hafting technologies were a relatively late innovation in this part of the world. Moreover, its regional uniqueness encourages us to abandon the perception of bone artefacts as a discrete class of material culture, and to adopt a new interpretative framework in which they are treated as manifestations of a more general class of artefacts that more typically were produced on perishable raw materials including wood.


Electroencephalogram in children with minor traumatic brain injury.
Mild traumatic brain injury (MTBI) is one of the most frequent causes for hospitalisation in childhood. Because of different guidelines in the management the diagnostic approach varies substantially. Apart from neuroimaging studies (CT, MRI, sonography) an electroencephalogram (EEG) is often performed without any evidence-based data supporting its use. Retrospective analysis of 150 children with MTBI (age 0-16 years), who were admitted to the Children's Hospital of the University of Saarland from January 2006 to December 2007. Mean age was 4.3 (SD 3.6) years: 55.3% were boys. The most common mechanisms of injury were: Minor fall <1 m of height (60%) and fall >1.5 m of height (10%). The most common symptoms were: one or more episodes of vomiting (60%), somnolence (26.7%) and headache (12.7%). On 118 patients an EEG was performed; 106 (89.8%) were normal, 11 (9.3%) pathological and 1 (0.9%) invalid because of artefacts. The pathological EEGs showed focal findings with localised slowing in nine cases, spike-wave complexes in one case and general slowing in one case. Of the 11 patients with pathological EEG, two had a CT scan, two a MRI and two had cranial sonography; all the neuro-imaging was normal. None of the children required neurosurgical intervention, had a negative outcome or showed persistent symptoms. The routine performance of an EEG after MTBI in children is not indicated because in most of the cases it is unrevealing, and may lead to unnecessary diagnostic procedures. Instead, children with MTBI should be closely monitored for possible clinical complications and neurological deterioration.


Selective calmodulin inhibition toward myosin light chain kinase by a new cerebral circulation improver, Ro 22-4839.
Ro 22-4839, a new cerebral circulation improver, has shown to be a potent calmodulin antagonist toward myosin light chain kinase (MLCK). It inhibited in vitro activity of calmodulin-activated cyclic AMP phosphodiesterase isolated from either bovine heart or brain and ATP-induced superprecipitation of chicken gizzard actomyosin with respective IC50 values of 20 microM, 17 microM, and 2.0 microM. The inhibitory action of Ro 22-4839 on the contractile system of the smooth muscle was demonstrated directly by its inhibition of chicken gizzard MLCK. Ro 22-4839 was found to potently inhibit MLCK with an IC50 value of 3.1 microM but was unable to inhibit the activity of MLCK rendered Ca2+/calmodulin independent by limited tryptic digestion. The inhibition of MLCK induced by Ro 22-4839 was completely overcome by addition of excess calmodulin. In contrast, Ro 22-4839 hardly inhibited calmodulin-activated Ca2+, Mg2+-ATPase from rat erythrocyte membrane or adenylate cyclase from rat brain. Use of hydrophobic fluorescence probes showed that Ro 22-4839 binds to the hydrophobic region of calmodulin like other calmodulin antagonists, trifluoperazine and W-7. However, the precise binding site of Ro 22-4839 to calmodulin is different from those of trifluoperazine and W-7, as suggested from differing IC50 values of these compounds against the probes. We conclude that Ro 22-4839 inhibits calmodulin-activated enzymes, most significantly of MLCK, highly specific to smooth muscle contractile systems by binding to the hydrophobic domain of the calmodulin and inducing its conformational change in the presence of calcium.


Overcoming the Maternal Care Crisis: How Can Lessons Learnt in Global Health Informatics Address US Maternal Health Outcomes?
Despite unprecedented spending, US maternal outcomes have worsened drastically over the past decade. In comparison, maternal outcomes of many Low and Middle-Income Countries (LMIC) have improved. Lessons learnt by their success may be applicable to the US. We performed a literature review to identify innovations that had met with success across LMIC, and should be considered for adoption in the US. mHealth and patient facing alerts, Telehealth, patient controlled health records, inclusion of patient relationship data in health information systems and positioning empowered community health workers as catalysts of maternal care delivery were identified as innovations worthy of further evaluation. These innovations were categorized into several themes; knowledge, technology, patient/community empowerment, coordination and process change. Tools that place informed and empowered patients and community members at the center of maternal care has greatly improved maternal outcomes, and are suitable to be considered for the US healthcare system.


The effects of hibernation and captivity on glucose metabolism and thyroid hormones in American black bear (Ursus americanus).
American black bears (Ursus americanus) have been shown to become transiently insulin resistant and hypothyroid during winter, but no studies have investigated these changes in long-term captive bears or in bears which remain awake year-round. Wild, captive hibernating, and captive nonhibernating bears were evaluated at times corresponding to three of their major physiologic stages: fall (hyperphagic stage), winter (hibernation stage), and summer (normal activity stage). Combined insulin and glucose tolerance tests and thyroid hormone profiles were performed on all bears during each stage. All three groups of bears had evidence of insulin resistance during the winter, as compared to the summer or fall, based on glucose tolerance curves. Analysis of thyroid hormone concentration varied and distinct patterns or similarities were not apparent. While obesity in captive American black bears is multifactorial, the finding that, regardless of their ability to hibernate, captive bears retain similar physiology to their wild counterparts indicates that captive bears' complex physiologic changes need to be addressed in their management.


Clinical, Genetic and Immunological Characteristics of Paediatric Autoimmune Polyglandular Syndrome Type 1 Patients in Slovenia.
Autoimmune polyglandular syndrome type 1 (APS-1) is an autosomal recessive disorder, caused by mutations in the AIRE gene. The major components of APS-1 are chronic mucocutaneous candidiasis (CMC), hypoparathyroidism (HP) and Addison's disease (AD). Clinical, genetic and immunological characteristics of Slovenian paediatric APS-1 patients were investigated. Existing medical records of 15 APS-1 patients were rewieved, when necessary, additional clinical and laboratory investigations were issued. AIRE gene analysis was performed to identify causative mutations, and autoantibodies against type I interferons were measured by luminescence immunoprecipitation system. Patients had one to eight different manifestations of the disease. CMC was present in all, HP in 12/15 (80 %) and AD in 8/15 (53 %) patients. Growth retardation, due to hyposomatotropism, growth hormone resistance, autoimmune thyroiditis, corticosteroid treatment, malabsorption or secretory failure of exocrine pancreas, was observed in altogether 7 (46 %) patients. Six different AIRE gene mutations were detected and p.R257X mutation was present in 63.3 % of pathological alleles. Antibodies against type I interferons were detected in all patients. APS-1 is a rare disorder with a broad spectrum of clinical manifestations, which, if unrecognized or inadequately treated may be fatal. AIRE gene mutational analysis and autoantibodies against type I interferons are important in early identification of the disease. The aetiology of growth retardation was shown to be extremely diverse, frequently caused by less characteristic manifestations. APS-1 may affect patients' quality of life in numerous ways, and may cause great psychosocial burden leading to depression and suicidal thoughts even in paediatric patients.


The antibody response to the flagella of Pseudomonas aeruginosa.
Mutants lacking flagella or fimbriae (pili) or both were used for the preparation and absorption of rabbit antisera against the flagella of Pseudomonas aeruginosa. The results of agglutination, immobilisation and complement-fixation tests indicate that the antisera obtained are specific for flagella. The incorporation of nitrate into semi-solid agar for motility and immobilisation tests was found useful for the selection of activity motile cells and for the demonstration of specific antibody to flagella.


Effect of soybean protein on coprostanol production and cholesterol metabolism in cholesterol-fed rats.
The effect of soybean protein on coprostanol production and cholesterol metabolism was studied in cholesterol-fed rats. Plasma cholesterol was decreased in the soybean protein diet group compared to the casein diet group. Although coprostanol was produced more in rats fed soybean protein than in those fed casein, no difference was observed in the levels of total neutral steroids at any part of the intestine. The activity of microbial conversion from cholesterol to coprostanol was evidently high in rats fed soybean protein. The total amount of neutral steroids excreted in feces had a tendency to increase. These data seem to indicate that the increase of the unabsorbed soybean protein causes the increase of intestinal coprostanol production.


Depersonalisation disorder: a contemporary overview.
Depersonalisation disorder is characterised by prominent depersonalisation and often derealisation, without clinically notable memory or identity disturbances. The disorder has an approximately 1 : 1 gender ratio with onset at around 16 years of age. The course of the disorder is typically long term and often continuous. Mood, anxiety and personality disorders are often comorbid with depersonalisation disorder but none predict symptom severity. The most common immediate precipitants of the disorder are severe stress, depression and panic, and marijuana and hallucinogen ingestion. Depersonalisation disorder has also been associated with childhood interpersonal trauma, in particular emotional maltreatment. Neurochemical findings have suggested possible involvement of serotonergic, endogenous opioid and glutamatergic NMDA pathways. Brain imaging studies in depersonalisation disorder have revealed widespread alterations in metabolic activity in the sensory association cortex, as well as prefrontal hyperactivation and limbic inhibition in response to aversive stimuli. Depersonalisation disorder has also been associated with autonomic blunting and hypothalamic-pituitary-adrenal axis dysregulation. To date, treatment recommendations and guidelines for depersonalisation disorder have not been established. There are few studies assessing the use of pharmacotherapy in this disorder. Medication options that have been reported include clomipramine, fluoxetine, lamotrigine and opioid antagonists. However, it does not appear that any of these agents have a potent anti-dissociative effect. A variety of psychotherapeutic techniques has been used to treat depersonalisation disorder (including trauma-focused therapy and cognitive-behavioural techniques), although again none of these have established efficacy to date. Overall, novel therapeutic approaches are clearly needed to help individuals experiencing this refractory disorder.


Endogenous Neuropeptide Nocistatin Is a Direct Agonist of Acid-Sensing Ion Channels (ASIC1, ASIC2 and ASIC3).
Acid-sensing ion channel (ASIC) channels belong to the family of ligand-gated ion channels known as acid-sensing (proton-gated) ion channels. Only a few activators of ASICs are known. These are exogenous and endogenous molecules that cause a persistent, slowly desensitized current, different from an acid-induced current. Here we describe a novel endogenous agonist of ASICs-peptide nocistatin produced by neuronal cells and neutrophils as a part of prepronociceptin precursor protein. The rat nocistatin evoked currents in X. laevis oocytes expressing rat ASIC1a, ASIC1b, ASIC2a, and ASIC3 that were very similar in kinetic parameters to the proton-gated response. Detailed characterization of nocistatin action on rASIC1a revealed a proton-like dose-dependence of activation, which was accompanied by a dose-dependent decrease in the sensitivity of the channel to the protons. The toxin mambalgin-2, antagonist of ASIC1a, inhibited nocistatin-induced current, therefore the close similarity of mechanisms for ASIC1a activation by peptide and protons could be suggested. Thus, nocistatin is the first endogenous direct agonist of ASICs. This data could give a key to understanding ASICs activation regulation in the nervous system and also could be used to develop new drugs to treat pathological processes associated with ASICs activation, such as neurodegeneration, inflammation, and pain.


Benefits of orotracheal and nasotracheal intubation in neonates requiring ventilatory assistance.
To investigate differences in orotracheal (OT) and nasotracheal (NT) intubation for ventilatory assistance, we randomly assigned 91 neonates to be intubated via either of the two routes: 46 infants were assigned to the OT group and 45 infants were assigned to the NT group. Inability to intubate the nostril in three neonates, and respiratory or cardiac instability during attempted NT intubation in three neonates, resulted in the assignment of 52 infants to the OT group and 39 infants to the NT group; patients in both groups were of comparable size, sex, and clinical problems. Initial malposition of the endotracheal tube and need to retape, reposition, or replace the tube during the mean duration of intubation of 247 +/- 42 hours for the OT group and 273 +/- 57 hours for the NT group were similar. Daily Gram stains of tracheal aspirates showed that inflammation (greater than or equal to ten polymorphonuclear cells per 400 power fields) was common (51% OT group, 53% NT group). Cultures grew potential pathogens in 37% of the patients from the OT group and 31% of the NT group. There was no difference in the clinical or radiologic incidence of pneumonia. Postextubation problems were comparable: atelectasis, 48% OT and 59% NT; stridor, 15% OT and 26% NT. OT intubation may be preferred for prolonged ventilatory assistance in neonates because of the relative ease of initial intubation.


Effects of osmotic pressure on the irreversible electroporation in giant lipid vesicles.
Irreversible electroporation (IRE) is a nonthermal tumor/cell ablation technique in which a series of high-voltage short pulses are used. As a new approach, we aimed to investigate the rupture of giant unilamellar vesicles (GUVs) using the IRE technique under different osmotic pressures (Π), and estimated the membrane tension due to Π. Two categories of GUVs were used in this study. One was prepared with a mixture of dioleoylphosphatidylglycerol (DOPG), dioleoylphosphatidylcholine (DOPC) and cholesterol (chol) for obtaining more biological relevance while other with a mixture of DOPG and DOPC, with specific molar ratios. We determined the rate constant (kp) of rupture of DOPG/DOPC/chol (46/39/15)-GUVs and DOPG/DOPC (40/60)-GUVs induced by constant electric tension (σc) under different Π. The σc dependent kp values were fitted with a theoretical equation, and the corresponding membrane tension (σoseq) at swelling equilibrium under Π was estimated. The estimated membrane tension agreed well with the theoretical calculation within the experimental error. Interestingly, the values of σoseq were almost same for both types of synthesized GUVs under same osmotic pressure. We also examined the sucrose leakage, due to large osmotic pressure-induced pore formation, from the inside of DOPG/DOPC/chol(46/39/15)-GUVs. The estimated membrane tension due to large Π at which sucrose leaked out was very similar to the electric tension at which GUVs were ruptured without Π. We explained the σc and Π induced pore formation in the lipid membranes of GUVs.


PolyGEE: a generalized estimating equation approach to the efficient and robust estimation of polygenic effects in large-scale association studies.
To quantify polygenic effects, i.e. undetected genetic effects, in large-scale association studies, we propose a generalized estimating equation (GEE) based estimation framework. We develop a marginal model for single-variant association test statistics of complex diseases that generalizes existing approaches such as LD Score regression and that is applicable to population-based designs, to family-based designs or to arbitrary combinations of both. We extend the standard GEE approach so that the parameters of the proposed marginal model can be estimated based on working-correlation/linkage-disequilibrium (LD) matrices from external reference panels. Our method achieves substantial efficiency gains over standard approaches, while it is robust against misspecification of the LD structure, i.e. the LD structure of the reference panel can differ substantially from the true LD structure in the study population. In simulation studies and in applications to population-based and family-based studies, we illustrate the features of the proposed GEE framework. Our results suggest that our approach can be up to 100% more efficient than existing methodology.


A study of interfering herpes simplex virus DNA preparations containing defective genomes of either class I or II and the identification of minimal requirements for interference.
Progeny DNA of herpes simplex virus type 1 (HSV-1) strain ANG from infections involving defective interfering virus particles (DI DNA) has been described to be of low infectivity in transfection assays due to the presence of viral genomes that interfere with plaque formation by infectious standard genomes. In this study it is shown that this observation applies both for DI DNA containing repetitive defective DNA of the class I type and for DI DNA containing class II-type defective DNA. Restriction endonucleases with recognition sites only in one class of repetitive defective DNA could be used to reduce selectively the interfering activity of DI DNA preparations containing the respective defective DNA in abundance. The results obtained directly implicate repetitive defective DNA as an interfering agent. Restriction endonucleases that create monomeric DNA fragments from class II HSV-1 ANG defective DNA did not abolish the interfering activity of DI DNA containing this type of defective DNA in high abundance, indicating that it is not simply the repetitive nature of defective DNA that is required for interference. Certain DNA fragments shorter than the repeat unit of repetitive defective DNA were still capable of causing interference even in the absence of cohesive single-stranded ends. The common location of cis recognition signals responsible for progeny DNA maturation and initiation of DNA replication on one DNA fragment, however, appeared to be a minimal requirement for interference by fragmented defective DNA.


What is nursing home quality and how is it measured?
In this commentary, we examine nursing home quality and indicators that have been used to measure nursing home quality. A brief review of the history of nursing home quality is presented that provides some context and insight into currently used quality indicators. Donabedian's structure, process, and outcome (SPO) model is used to frame the discussion. Current quality indicators and quality initiatives are discussed, including those included in the Facility Quality Indicator Profile Report, Nursing Home Compare, deficiency citations included as part of Medicare/Medicaid certification, and the Advancing Excellence Campaign. Current quality indicators are presented as a mix of structural, process, and outcome measures, each of which has noted advantages and disadvantages. We speculate on steps that need to be taken in the future to address and potentially improve the quality of care provided by nursing homes, including report cards, pay for performance, market-based incentives, and policy developments in the certification process. Areas for future research are identified throughout the review. We conclude that improvements in nursing home quality have likely occurred, but improvements are still needed.


Fabrication of Iron-Containing Biochar by One-Step Ball Milling for Cr(VI) and Tetracycline Removal from Wastewater.
Simple ball milling technology can simultaneously improve the adsorption performance of adsorbents for heavy metals and organic pollutants and has attracted increasing attention. Iron-modified biochar (Fe@MBC) was prepared by one-step ball milling, and the characterization results proved that FeCl3 was successfully loaded on biochar. The removal rates of Cr(VI) and tetracycline hydrochloride (TC) by Fe@MBC were increased by 88.27% and 82.64% compared with BC. The average pore size, oxygen-containing functional groups and graphitization degree of Fe@MBC are higher than those of BC, which is more conducive to promoting adsorption. The adsorption isotherms show that the adsorption of Cr(VI) and TC on the Fe@MBC surface conforms to the Langmuir type of single-layer adsorption and the Freundlich model of multilayer adsorption, respectively. The maximum adsorption capacities of Cr(VI) and TC are 25.46 and 66.91 mg·g-1, respectively. Kinetic experiments show that the adsorption process is more consistent with the pseudo-second-order model of chemical adsorption. The adsorption process of Cr(VI) and TC on the Fe@MBC surface is a spontaneous endothermic process that becomes more obvious as the temperature increases. The increase in solution pH has a significant impact on the removal rate of Fe@MBC. When the pH value increased from 3 to 11, the adsorption rates decreased by 53.74% and 17.16%, respectively. The presence of PO43-, CO32-, K+, and Cu2+ significantly affects the adsorption of TC by Fe@MBC, and PO43- and CO32- also affect the adsorption of Cr(VI). Mechanistic studies show that ion exchange, electrostatic interaction, pore filling, and hydrogen bonding contribute to the removal of Cr(VI) and TC by Fe@MBC. The removal mechanism of Cr(VI) also involves complexation and redox reactions, and the removal mechanism of TC involves π-π bonds and van der Waals forces. The results show that Fe@MBC is a green and efficient adsorbent.


High-level arsenite removal from groundwater by zero-valent iron.
The objectives of this study were to conduct batch and column studies to (i) assess the effectiveness of zero-valent iron for arsenic remediation in groundwater, (ii) determine removal mechanisms of arsenic, and (iii) evaluate implications of these processes with regard to the stability of arsenic and long-term remedial performance of the permeable reactive barrier (PRB) technology. A high concentration arsenic solution (50 mg l(-1)) was prepared by using sodium arsenite (arsenic (III)) to simulate groundwater at a heavily contaminated Superfund site in the USA. Batch studies indicate that the removal of arsenic is a two-step reaction with fast initial disappearance of arsenite followed by a slow subsequent removal process. Flow-through columns were conducted at a flow rate of 17 ml h(-1) under reducing conditions for 6.6 mo. Kinetic analysis suggested that arsenic removal behaves as a zero-order reaction at high arsenic concentrations. Arsenic removal rate constants decreased with time and arsenic breakthrough was observed in the column study. Arsenic removal capacity of zero-valent iron was determined to be approximately 7.5 mg As/g Fe. Carbonate green rust was identified from the analysis of surface precipitates; arsenite uptake by green rust may be a major mechanism responsible for arsenic remediation by zero-valent iron. Analysis of HCl-extractable arsenic from iron samples indicated that approximately 28% of arsenic was in the form of arsenate suggesting that a surface oxidation process was involved in the arsenic removal with zero-valent iron.


Limited interactions between space- and feature-based attention in visually sparse displays.
Top-down visual attention selectively filters sensory input so relevant information receives preferential processing. Feature-based attention (FBA) enhances the representation of relevant low-level features, whereas space-based attention (SBA) enhances information at relevant location(s). The present study investigates whether the unique influences of SBA and FBA combine to facilitate behavior in a perceptually demanding discrimination task. We first demonstrated that, independently, both color and location pre-cues could effectively direct attention to facilitate perceptual decision making of a target. We then examined the combined effects of SBA and FBA in the same design by deploying a predictive color arrow pre-cue. Only SBA effects were observed in performance accuracy and reaction time. However, we detected a reaction time cost when a valid spatial cue was paired with a feature cue. A computational perceptual decision-making model largely provided converging evidence that contributions from FBA were restricted to facilitating the speed with which the relevant item was identified. Our results suggest that both selection mechanisms can be used in isolation to resolve a perceptually challenging target in a sparse display, but with little additive perceptual benefit when cued simultaneously. We conclude that there is at least some higher order interdependence between space-based and feature-based selection during decision making under specific conditions.


Refugee experiences of general practice in countries of resettlement: a literature review.
Refugees and asylum seekers often struggle to use general practice services in resettlement countries. To describe and analyse the literature on the experiences of refugees and asylum seekers using general practice services in countries of resettlement. Literature review using systematic search and narrative data extraction and synthesis methodologies. International, peer-reviewed literature published in English language between 1990 and 2013. Embase, Ovid MEDLINE, PsycINFO, CSA Sociological Abstracts, and CINAHL databases were searched using the terms: refugee, asylum seeker, experience, perception, doctor, physician, and general practitioner. Titles, abstracts and full texts were reviewed and were critically appraised. Narrative themes describing the refugee or asylum seeker's personal experiences of general practice services were identified, coded, and analysed. From 8722 papers, 85 were fully reviewed and 23 included. These represented the experiences of approximately 864 individuals using general practice services across 11 countries. Common narrative themes that emerged were: difficulties accessing general practice services, language barriers, poor doctor-patient relationships, and problems with the cultural acceptability of medical care. The difficulties refugees and asylum seekers experience accessing and using general practice services could be addressed by providing practical support for patients to register, make appointments, and attend services, and through using interpreters. Clinicians should look beyond refugee stereotypes to focus on the needs and expectations of the individual. They should provide clear explanations about unfamiliar clinical processes and treatments while offering timely management.


Prolonged toxic effects after cocaine challenge in butyrylcholinesterase/plasma carboxylesterase double knockout mice: a model for butyrylcholinesterase-deficient humans.
Death and toxicity after cocaine use do not correlate with cocaine blood levels. One explanation for this observation is that cocaine abusers may posses one or more of the 58 possible known mutations in the butyrylcholinesterase gene (BCHE). Butyrylcholinesterase (BChE) serves as the primary cocaine hydrolase producing a nontoxic product ecgonine methyl ester. A reduction in endogenous levels of BChE may result in increased metabolism by hepatic carboxylesterase to produce norcocaine, a toxic product. Humans have carboxylesterase in tissues but not in plasma, whereas wild-type mice have significant amounts of carboxylesterase in tissues and plasma. Knockout mice with no plasma carboxylesterase were created to eliminate the contribution of plasma carboxylesterase in cocaine hydrolysis, thereby simulating human enzyme levels. This study tested the hypothesis that reductions in BChE such as those in humans with BChE mutations contribute to increased toxicity after cocaine use. Carboxylesterase and BChE double knockout mice, models for humans with BChE deficiency, were challenged with a nonlethal dose of 100 mg/kg (-)-cocaine. Carboxylesterase/BChE double knockout mice demonstrated toxic signs significantly longer than did wild-type and carboxylesterase knockout mice. The carboxylesterase/BChE-deficient mice took approximately 2.5 times as long to recover from cocaine toxicities, including the following: hypothermia, hyperactivity, stereotypical behavior, ocular effects, and dorsiflexion of the tail. The carboxylesterase/BChE double knockout mouse model demonstrates the importance of endogenous BChE for protection against cocaine toxicity and provides an in vivo system for studying drug sensitivity of humans who carry a BChE mutation.


A double-blind comparison of aspirin and pirprofen in the treatment of rheumatoid arthritis.
Pirprofen (600 mg, 800 mg) and aspirin (3,600 mg) were compared in 30 outpatients (33-67 yr old) with definite or classical rheumatoid arthritis. After 10 wk of treatment with either pirprofen dose, the number of painful joints, grip strength, and the duration of morning stiffness improved significantly. Only the number of painful joints improved significantly with aspirin. The erythrocyte sedimentation rate decreased with aspirin and 600 mg pirprofen but increased (significantly) with 800 mg pirprofen. The differences in improvement between the 3 treatment groups were not statistically significant. Gastrointestinal disturbances were the most frequently reported side-effects in each treatment group. Central nervous system effects and tinnitus were reported by more patients in the aspirin group than in either of the pirprofen groups.


Oncolytic measles and vesicular stomatitis virotherapy for endometrial cancer.
Current adjuvant therapy for advanced-stage, recurrent, and high-risk endometrial cancer (EC) has not reduced mortality from this malignancy, and novel systemic therapies are imperative. Oncolytic viral therapy has been shown to be effective in the treatment of gynecologic cancers, and we investigated the in vitro and in vivo efficacy of the Edmonston strain of measles virus (MV) and vesicular stomatitis virus (VSV) on EC. Human EC cell lines (HEC-1-A, Ishikawa, KLE, RL95-2, AN3 CA, ARK-1, ARK-2, and SPEC-2) were infected with Edmonston strain MV expressing the thyroidal sodium iodide symporter, VSV expressing either human or murine IFN-β, or recombinant VSV with a methionine deletion at residue 51 of the matrix protein and expressing the sodium iodide symporter. Xenografts of HEC-1-A and AN3 CA generated in athymic mice were treated with intratumoral MV or VSV or intravenous VSV. In vitro, all cell lines were susceptible to infection and cell killing by all 3 VSV strains except KLE. In addition, the majority of EC cell lines were defective in their ability to respond to type I IFN. Intratumoral VSV-treated tumors regressed more rapidly than MV-treated tumors, and intravenous VSV resulted in effective tumor control in 100% of mice. Survival was significantly longer for mice treated with any of the 3 VSV strains compared with saline. VSV is clearly more potent in EC oncolysis than MV. A phase 1 clinical trial of VSV in EC is warranted.


Benzodiazepine Use and the Risk of Dementia in the Elderly Population: An Umbrella Review of Meta-Analyses.
The prevalence of dementia among the elderly is high, and it is the leading cause of death globally. However, the relationship between benzodiazepine use and dementia risk has produced inconsistent results, necessitating an updated review of the evidence. To address this, we conducted an umbrella review of meta-analyses to summarize the available evidence on the association between benzodiazepine use and dementia risk and evaluate its credibility. We systematically evaluated the meta-analyses of observational studies that examined the connection between benzodiazepine use and dementia risk. For each meta-analysis, we collected the overall effect size, heterogeneity, risk of bias, and year of the most recent article and graded the evidence based on pre-specified criteria. We also used AMSTAR, a measurement tool to evaluate systematic reviews, to assess the methodological quality of each study. Our review included five meta-analyses encompassing 30 studies, and the effect size of the association between benzodiazepine use and dementia risk ranged from 1.38 to 1.78. Nonetheless, the evidence supporting this relationship was weak, and the methodological quality of the studies included was low. In conclusion, our findings revealed limited evidence of a link between benzodiazepine use and dementia risk, and more research is required to determine a causal connection. Physicians should only prescribe benzodiazepine for appropriate indications.


Patients with liver cirrhosis show worse survival if decompensation occurs later during course of disease than at diagnosis.
Liver cirrhosis is characterized by a silent phase until decompensation, which is defined by onset of ascites, variceal bleeding, or encephalopathy. Although it is presumed that the survival of decompensated patients is the same regardless of when decompensation occurs, data to support this are scarce. We aimed to study the impact of time of decompensation on the clinical course and survival of patients with cirrhosis in a large population-based cohort. We used medical registries to define a 10-year cohort of 1317 patients with incident liver cirrhosis in the Scania region of Sweden. Medical records were reviewed. Patients were followed until December 2011, and for death or transplantation until December 2014. In the cohort, 629 patients were decompensated at diagnosis, of which 505 had ascites and 44 variceal bleeding only. During follow-up, 228 patients developed ascites and 39 variceal bleeding as first complication. Patients with ascites as first complication showed worse survival than patients who had ascites at diagnosis. (5-year survival 33% vs. 15%, HR 1.60 (95% CI 1.34-1.90)). This difference persisted after adjustment for confounders, including hepatocellular cancer (HR 1.38 (95% CI 1.15-1.67)). Worse survival was also seen when bleeding from varices occurred during follow-up rather than at diagnosis. Our results provide evidence for an association between transplantation-free survival after decompensation and the time of decompensation in liver cirrhosis, with worse survival when decompensation occurs during follow-up, thus challenging the generally held, view that the survival after decompensation is independent of when decompensation occurs.


VIP+ interneurons control neocortical activity across brain states.
GABAergic interneurons are positioned to powerfully influence the dynamics of neural activity, yet the interneuron-mediated circuit mechanisms that control spontaneous and evoked neocortical activity remains elusive. Vasoactive intestinal peptide (VIP+) interneurons are a specialized cell class which synapse specifically on other interneurons, potentially serving to facilitate increases in cortical activity. In this study, using in vivo Ca(2+) imaging, we describe the interaction between local network activity and VIP+ cells and determine their role in modulating neocortical activity in mouse visual cortex. VIP+ cells were active across brain states including locomotion, nonlocomotion, visual stimulation, and under anesthesia. VIP+ activity correlated most clearly with the mean level of population activity of nearby excitatory neurons during all brain states, suggesting VIP+ cells enable high-excitability states in the cortex. The pharmacogenetic blockade of VIP+ cell output reduced network activity during locomotion, nonlocomotion, anesthesia, and visual stimulation, suggesting VIP+ cells exert a state-independent facilitation of neural activity in the cortex. Collectively, our findings demonstrate that VIP+ neurons have a causal role in the generation of high-activity regimes during spontaneous and stimulus evoked neocortical activity.


An Arabidopsis thaliana protein homologous to cyanobacterial high-light-inducible proteins.
An Arabidopsis thaliana cDNA clone encoding a novel 110 amino acid thylakoid protein has been sequenced. The in vitro synthesized protein is taken up by intact chloroplasts, inserted into the thylakoid membrane and the transit peptide is cleaved off during this process. The mature protein is predicted to contain 69 amino acids, to form one membrane-spanning alpha-helix and to have its N-terminus at the stromal side of the thylakoid membrane. The protein showed similarity to the LHC, ELIP and PsbS proteins of higher plants, but more pronounced to the high-light-inducible proteins (HLIPs) of cyanobacteria and red algae, to which no homologue previously has been detected in higher plants. As for HLIP and ELIP, high light increases the mRNA levels of the corresponding gene. Sequence comparisons indicate that the protein may bind chlorophyll and form dimers in the thylakoid membrane. The level of expression of the protein seems to be far lower than that of normal PSI and PSII subunits.


[The first experience of iris-fixated intraocular lens implantation in patients with open-angle glaucoma].
The results of iris-claw intraocular lens (IOL) implantation in patients with lens dislocation, deficiency of capsule support in combination with glaucoma are presented. Iris-claw "Artizan" IOL was used in 16 eyes. IOL was implanted through 5 mm corneal incision into the posterior chamber with haptic fixated to iris stroma. Implantation of this IOL model is minimally traumatic, provides favorable visual outcome and does not lead to intraocular pressure decompensation in patients with glaucoma.


No evidence of positive assortative mating for genetic quality in fruit flies.
In sexual populations, the effectiveness of selection will depend on how gametes combine with respect to genetic quality. If gametes with deleterious alleles are likely to combine with one another, deleterious genetic variation can be more easily purged by selection. Assortative mating, where there is a positive correlation between parents in a phenotype of interest such as body size, is often observed in nature, but does not necessarily reveal how gametes ultimately combine with respect to genetic quality itself. We manipulated genetic quality in fruit fly populations using an inbreeding scheme designed to provide an unbiased measure of mating patterns. While inbred flies had substantially reduced reproductive success, their gametes did not combine with those of other inbred flies more often than expected by chance, indicating a lack of positive assortative mating. Instead, we detected a negative correlation in genetic quality between parents, i.e. disassortative mating, which diminished with age. This pattern is expected to reduce the genetic variance for fitness, diminishing the effectiveness of selection. We discuss how mechanisms of sexual selection could produce a pattern of disassortative mating. Our study highlights that sexual selection has the potential to either increase or decrease genetic load.


The application of mean field theory to image motion estimation.
Previously, Markov random field (MRF) model-based techniques have been proposed for image motion estimation. Since motion estimation is usually an ill-posed problem, various constraints are needed to obtain a unique and stable solution. The main advantage of the MRF approach is its capacity to incorporate such constraints, for instance, motion continuity within an object and motion discontinuity at the boundaries between objects. In the MRF approach, motion estimation is often formulated as an optimization problem, and two frequently used optimization methods are simulated annealing (SA) and iterative-conditional mode (ICM). Although the SA is theoretically optimal in the sense of finding the global optimum, it usually takes many iterations to converge. The ICM, on the other hand, converges quickly, but its results are often unsatisfactory due to its "hard decision" nature. Previously, the authors have applied the mean field theory to image segmentation and image restoration problems. It provides results nearly as good as SA but with much faster convergence. The present paper shows how the mean field theory can be applied to MRF model-based motion estimation. This approach is demonstrated on both synthetic and real-world images, where it produced good motion estimates.


Applicability of a pre-established set of facial proportions from frontal photographs in forensic age estimation of a Brazilian population.
Child pornography on the internet is one of the crimes with highest increasing incidence worldwide. In this specific type of crime, the victim's age has important legal implications. To overcome the lack of scientifically established protocols, European researchers explored and proposed a set of facial proportions obtained from images to estimate age. Within a validation scope, the present study aimed to test the applicability of morphological proportions from frontal photographs of the face to estimate age in a Brazilian population. Standardized frontal view photographs from 800 Brazilians (400 females and 400 males) homogeneously distributed in 4 age groups (6, 10, 14 and 18 years ± 30 days) were randomly selected from a Civilian Database of the Brazilian Federal Police. The selected images were analyzed with the aid of cephalometric landmarks. After landmarking the photographs, eighteen metric relations pre-established by Cattaneo et al. (C. Cattaneo, Z. Obertová, M. Ratnayake, L. Marasciuolo, J. Tutkuviene, P. Poppa, D. Gibelli, P. Gabriel, S. Ritz-Timme, Can facial proportions taken from images be of use for ageing in cases of suspected child pornography? A pilot study, Int. J. Leg. Med. 126 2012 139-144) were assessed and analyzed through parametric statistical tests and discriminant analysis. Two indexes had a moderate correlation with age, while ten had a weak correlation and six were not correlated with age. Eleven indexes were statistically different between sexes (p < 0.05). The discriminant analysis showed that 49.6% of the pooled sample was correctly classified into the respective age group. This percentage increased when each sex was analyzed separately: 50.2% for females and 53.5% for males. The set of facial proportions from frontal images proposed by Cattaneo et al. (2012) is related to facial development. As expected, the discriminant power of this approach did not reach optimal effectiveness in the Brazilian sample. In practice, this age estimation method must be adapted for more reliable application in Brazilians.


A preliminary study of functional magnetic resonance imaging response during verbal encoding among adolescent binge drinkers.
Binge alcohol use is common among teenagers with 28% of 12th graders reporting getting drunk in the past month. Chronic heavy drinking has been associated with verbal learning and memory deficits in adolescents and adults, yet verbal encoding in less frequently drinking teens has not yet been studied. Here, we examined functional magnetic resonance imaging (fMRI) response during verbal encoding among adolescent binge drinkers. Participants recruited from local high schools were of ages 16-18 and consisted of 12 binge drinkers and 12 demographically similar nondrinkers. Participants were all nonsmokers, and drinkers were abstinent from alcohol for an average of 33 days at the time of scanning. Participants performed a verbal paired associates learning task during fMRI acquisition. Drinkers recalled marginally fewer words than nondrinkers (P=.07). Compared with nondrinkers, bingers showed more response in right superior frontal and bilateral posterior parietal cortices but less response in occipital cortex during novel encoding (Ps<.05, clusters >1,512microL). In addition, controls showed significant activation in the left hippocampus during novel encoding, whereas binge drinkers did not. Adolescent binge drinkers demonstrated (1) more response than nondrinkers in frontal and parietal regions, which could suggest greater engagement of working memory systems during encoding; (2) no hippocampal activation to novel word pairs; and (3) slightly poorer word pair recall, which could indicate disadvantaged processing of novel verbal information and a slower learning slope. Longitudinal studies will be needed to ascertain the degree to which emergence of binge drinking is linked temporally to these brain response patterns.


An integrated newborn care kit (iNCK) to save newborn lives and improve health outcomes in Gilgit Baltistan (GB), Pakistan: study protocol for a cluster randomized controlled trial.
Ongoing high neonatal mortality rates (NMRs) represent a global challenge. In 2021, of the 5 million deaths reported worldwide for children under five years of age, 47% were newborns. Pakistan has one of the five highest national NMRs in the world, with an estimated 39 neonatal deaths per 1,000 live births. Reducing newborn deaths requires sustainable, evidence-based, and cost-effective interventions that can be integrated within existing community healthcare infrastructure across regions with high NMR. This pragmatic, community-based, parallel-arm, open-label, cluster randomized controlled trial aims to estimate the effect of Lady Health Workers (LHWs) providing an integrated newborn care kit (iNCK) with educational instructions to pregnant women in their third trimester, compared to the local standard of care in Gilgit-Baltistan, Pakistan, on neonatal mortality and other newborn and maternal health outcomes. The iNCK contains a clean birth kit, 4% chlorhexidine topical gel, sunflower oil emollient, a ThermoSpot™ temperature monitoring sticker, a fleece blanket, a click-to-heat reusable warmer, three 200 μg misoprostol tablets, and a pictorial instruction guide and diary. LHWs are also provided with a handheld scale to weigh the newborn. The primary study outcome is neonatal mortality, defined as a newborn death in the first 28 days of life. This study will generate policy-relevant knowledge on the effectiveness of integrating evidence-based maternal and newborn interventions and delivering them directly to pregnant women via existing community health infrastructure, for reducing neonatal mortality and morbidity, in a remote, mountainous area with a high NMR. NCT04798833, March 15, 2021.


Emerging Trends and New Developments in Disaster Research after the 2008 Wenchuan Earthquake.
On the tenth anniversary of the 2008 Wenchuan Earthquake, investigating the evolution of disaster science is worthwhile and can be used to improve the future execution of disaster risk management. Based on more than 55,786 articles on the relative topic of "Disaster" derived from the Web of Science Core Collection from 1999⁻2017, this study employs CiteSpace and Google Earth to identify and visualize the spatial distribution of publications, bursts of keywords and categories, highly cited references, and interdisciplinary levels and then identify the emerging trends of disaster research over the past 20 years. The results show that the earthquake indeed jumpstarted a massive wave of disaster research around the world and increased international cooperation over the last decade. However, in terms of both the quantity and quality of publications in disaster research fields, China is lagging behind the U.S. and European countries. Moreover, although designing disaster prevention and mitigation strategies is a new popular field of disaster science, geological environment changes and geologic hazards triggered by earthquakes are more popular research topics than disaster emergency and recovery. In addition, the transdisciplinary level of disaster science increased after the earthquake. This interdisciplinary characteristic of disaster science gradually increased in popularity, which demonstrates that people can learn from catastrophes. These emerging trends could serve as a scientific basis to clearly understand disaster science progress over the last 20 years and provide a reference for rapidly identifying frontier issues in disaster science.


Extracapsular nodal extension and tumor deposits in head and neck squamous cell carcinoma.
Tumor deposits (TDs) are an infrequently mentioned feature of head and neck squamous cell carcinoma (HNSCC) that are currently grouped under extranodal extension (ENE) in the AJCC 8th edition of HNSCC TNM staging. The prognostic implication of TDs in comparison to ENE remains uncertain. This observational, retrospective, non-randomized study evaluated patients with HNSCC who underwent initial surgical resection, with neck dissection and adjuvant radiotherapy ± chemotherapy. Clinical variables were considered, and statistical analyses were conducted to compare time progression and overall survival (OS) in patients with TDs against those with ENE. Of the 71 patients included in the study, 50 were diagnosed with ENE (pN2a-ENE in 38 patients and pN3b-ENE in 12), while 21 had TDs ± ENE. The median time to progression was significantly different based on the presence of ENE or TDs (p = .002) and pN2a-ENE/pN3b-ENE or TDs (p = .007). The three-year OS was 55.7% for the entire group, 60.4% in ENE and 38.4% in TDs (p = .021). The OS difference between the pN2a-ENE, pN3b-ENE, and the TDs group was also significant (p = .05). The hazard ratio between ENE and TDs was Exp (B) 4.341 (p = .044). TDs in HNSCC are associated with a lower OS than ENE, despite intensified adjuvant therapy. Our results confirm a better prognosis for pN2a-ENE vs. pN3b-ENE, and pN3b-ENE vs. TDs. TDs may serve as an indicator of poor prognosis and require separate TNM classification in HNSCC staging. Larger studies are needed to evaluate TDs impact on treatment strategies and outcomes.


Positive technology as a driver for health engagement.
Despite the fact that older adults are healthier than in the past, the current trend of an ageing population implies an increased risk and severity of chronic diseases. Low-resource healthcare systems face increased organizational healthcare costs, which is likely to result in an allocation of limited health resources. Healthcare organizations themselves must deal with patients' increasing need for a more active role in all the steps of the care & cure process. Technological advances may play a crucial role in sustaining people's health management in daily life, but only if it is "ecologically" designed and well-attuned to people's health needs and expectations. Healthcare is more and more called to orient innovative research approaches that recognize the crucial role of a person's engagement in health and well-being. This will enable patients to reach a higher quality of life and achieve a general psychophysical well-being. Thus, positive technological innovation can sustain people's engagement in health and invoke community empowerment, as we shall discuss in this document.


Circulating adiponectin levels and mortality in elderly men with and without cardiovascular disease and heart failure.
High adiponectin levels have been associated with reduced cardiovascular risk but have been shown to predict mortality in those at high risk for vascular disease. We examined the relationship between adiponectin levels and mortality in older men with and without diagnosed cardiovascular disease (CVD) and heart failure. Prospective study of 4046 men aged 60 to 79 years drawn from general practices in 24 British towns and followed up for a mean of 6 years, during which 734 deaths occurred. The men were divided into the following groups according to the presence of physician-diagnosed CVD and heart failure: (1) those with no CVD or heart failure; (2) those with CVD but without heart failure; and (3) those with heart failure (with or without CVD). After adjustment for a wide range of baseline characteristics, adiponectin levels were positively associated with significantly increased all-cause and CVD mortality in men with no diagnosed CVD or heart failure (top third vs bottom third adjusted relative risk, 1.55 [95% confidence interval (CI), 1.19-2.02; P = .002 for trend] vs 1.53 [95% CI, 1.03-2.27; P = .02 for trend]), as well as in men with diagnosed heart failure ([adjusted relative risk, 2.37 [95% CI, 0.64-8.79; P = .04 for trend] vs 3.43 [95% CI, 0.54-21.70; P = .008 for trend]). No association was seen in those with diagnosed CVD without heart failure. Adjustment for weight loss and renal function made minor differences to these relationships. In older men, high adiponectin levels are associated with increased all-cause and CVD mortality in those with heart failure and those free of CVD. Such observations suggest that adiponectin levels may reflect a balance of both protective and harmful factors.


Determinants of breastfeeding initiation among mothers in Sydney, Australia: findings from a birth cohort study.
Breastfeeding has short-term and long-term benefits for both the infant and the mother. The objective of this study was to identify the incidence of breastfeeding initiation among women in South Western Sydney, and the factors associated with the initiation of breastfeeding. Child and Family Health Nurses recruited mother-infant dyads (n = 1035) to the Healthy Smiles Healthy Kids birth study in South Western Sydney, an ethnically and socio-economically diverse area, at the first post-natal home visit. A sample of 935 women completed a structured, interviewer-administered questionnaire at 8 weeks. Multivariate logistic regression analysis was used to identify those factors independently associated with the initiation of breastfeeding. In total, 92% of women (n = 860) commenced breastfeeding in hospital. Women who completed a university degree were more likely to initiate breastfeeding compared to those who did not complete high school (AOR = 7.16, 95% CI 2.73, 18.79). Vietnamese women had lower odds of breastfeeding initiation compared to Australian born women (AOR = 0.34. 95% CI 0.13, 0.87). Women who had more than one child were less likely to breastfeed than those who had one child (AOR = 0.38, 95% CI 0.19, 0.79). Women who gave birth via a caesarean section were less likely to breastfeed their baby compared to those who had a vaginal delivery (AOR = 0.27, 95% CI 0.14, 0.52). Women who drank alcohol during pregnancy had 72% lower odds to breastfeed compared to those who did not drink alcohol during pregnancy (AOR = 0.28, 95% CI 0.11, 0.71). Women who reported that their partner preferred breastfeeding were more likely to initiate breastfeeding (AOR = 11.77, 95% CI 5.73, 24.15) and women who had chosen to breastfeed before pregnancy had more than 2.5 times the odds of breastfeeding their baby compared to those women who made their decision either during pregnancy or after labour (AOR = 2.80, 95% CI 1.31, 5.97). Women with lower levels of education, who consume alcohol during pregnancy, have more than one child, and make infant feeding decision after becoming pregnant, and those born in Vietnam should be targeted when implementing breastfeeding promotion programs. Further, women who deliver by caesarean section require additional breastfeeding support post-delivery and it is important to include fathers in breastfeeding related decisions and encourage them to participate in antenatal programs.


Sound iconicity of abstract concepts: Place of articulation is implicitly associated with abstract concepts of size and social dominance.
The concept of sound iconicity implies that phonemes are intrinsically associated with non-acoustic phenomena, such as emotional expression, object size or shape, or other perceptual features. In this respect, sound iconicity is related to other forms of cross-modal associations in which stimuli from different sensory modalities are associated with each other due to the implicitly perceived correspondence of their primal features. One prominent example is the association between vowels, categorized according to their place of articulation, and size, with back vowels being associated with bigness and front vowels with smallness. However, to date the relative influence of perceptual and conceptual cognitive processing on this association is not clear. To bridge this gap, three experiments were conducted in which associations between nonsense words and pictures of animals or emotional body postures were tested. In these experiments participants had to infer the relation between visual stimuli and the notion of size from the content of the pictures, while directly perceivable features did not support-or even contradicted-the predicted association. Results show that implicit associations between articulatory-acoustic characteristics of phonemes and pictures are mainly influenced by semantic features, i.e., the content of a picture, whereas the influence of perceivable features, i.e., size or shape, is overridden. This suggests that abstract semantic concepts can function as an interface between different sensory modalities, facilitating cross-modal associations.


What do we mean by "tailoring" of medical information during clinical interactions?
Although medical information is essential for all patients, information needs and information processing capacities vary between individual patients and over time and context, within patients. Therefore, it is often recommended to "tailor" medical information to individual patients during clinic visits. However, there is a lack of consensus on what "tailoring" in clinical interactions represents since the definitions provided in the literature thus far generally regard tailoring of written text, rather than in dialogue during face-to-face interactions. To provide clinicians with guidance on how to tailor information to individual patients and to allow researchers to assess the effectiveness thereof, clarity is urgently needed regarding what "tailoring" actually means and what it entails in practice. In this paper we outline the current challenges of applying the concept of "tailoring" to the clinical setting and present existing definitions. Importantly, we introduce a new working definition of the concept that encompasses essential informational and dialogic components. We believe this provisional definition promotes much-needed conceptual precision in how communication researchers and educators define and assess tailored information provision in clinical consultations.


Delafloxacin: Place in Therapy and Review of Microbiologic, Clinical and Pharmacologic Properties.
Delafloxacin (formerly WQ-3034, ABT492, RX-3341) is a novel fluoroquinolone chemically distinct from currently marketed fluoroquinolones with the absence of a protonatable substituent conferring a weakly acidic character to the molecule. This property results in increased intracellular penetration and enhanced bactericidal activity under acidic conditions that characterize the infectious milieu at a number of sites. The enhanced potency and penetration in low pH environments contrast what has been observed for other zwitterionic fluoroquinolones, which tend to lose antibacterial potency under acidic conditions, and may be particularly advantageous against methicillin-resistant Staphylococcus aureus, for which the significance of the intracellular mode of survival is increasingly being recognized. Delafloxacin is also unique in its balanced target enzyme inhibition, a property that likely explains the very low frequencies of spontaneous mutations in vitro. Delafloxacin recently received US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections and is currently being evaluated in a phase 3 trial among patients with community-acquired pneumonia. In the current era of a heightened awareness pertaining to collateral ecologic damage, safety issues and antimicrobial stewardship principles, it is critical to describe the unique properties of delafloxacin and define its potential role in therapy. The purpose of this article is to review available data pertaining to delafloxacin's biochemistry, pharmacokinetic/pharmacodynamics characteristics, in vitro activity and potential for resistance selection as well as current progress in clinical trials to ultimately assist clinicians in selecting patients who will benefit most from the distinctive properties of this agent.


Vitamin B2 intake and colorectal cancer risk; results from the Nurses' Health Study and the Health Professionals Follow-Up Study cohort.
Vitamin B2 serves as a cofactor to enhance one-carbon metabolism, maintain mucous membranes, and has been implicated in lowering colorectal cancer (CRC) risk. However, few prospective studies have examined the association between vitamin B2 intake and CRC. In this study, we estimated the associations between vitamin B2 intake and CRC risk using the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS) cohorts. Vitamin B2 intake was measured by a validated food frequency questionnaire every 4 years. Among 100,033 women in the NHS and 44,007 men in the HPFS we documented a total of 3,037 incident CRC cases (2,093 women and 944 men) during 24-26 years of follow-up until 2010. Intakes of total (from food and supplements), dietary (from food only), and supplemental vitamin B2 were inversely related to CRC risk in age-adjusted analysis in NHS. However, the association was attenuated and no longer statistically significant in multivariate analysis (p-trend ≥0.08). The pooled multivariate relative risks (95% confidence interval) comparing individuals in the extreme quintiles of intakes were 0.93 (0.81-1.06) for total vitamin B2, 0.89 (0.61-1.28) for dietary vitamin B2 and 0.94 (0.81-1.08) for supplemental vitamin B2. These associations of total vitamin B2 intake were similar for risk of CRC with varying lag-time periods (0-4, 4-8, 8-12 or 12-16 years), for risk of CRC subtypes by tumor location, and across strata of intake of folate or alcohol. Our prospective data do not support a beneficial role of vitamin B2 intake in lowering incidence of CRC.


A Parallel Product-Convolution approach for representing the depth varying Point Spread Functions in 3D widefield microscopy based on principal component analysis.
We address the problem of computational representation of image formation in 3D widefield fluorescence microscopy with depth varying spherical aberrations. We first represent 3D depth-dependent point spread functions (PSFs) as a weighted sum of basis functions that are obtained by principal component analysis (PCA) of experimental data. This representation is then used to derive an approximating structure that compactly expresses the depth variant response as a sum of few depth invariant convolutions pre-multiplied by a set of 1D depth functions, where the convolving functions are the PCA-derived basis functions. The model offers an efficient and convenient trade-off between complexity and accuracy. For a given number of approximating PSFs, the proposed method results in a much better accuracy than the strata based approximation scheme that is currently used in the literature. In addition to yielding better accuracy, the proposed methods automatically eliminate the noise in the measured PSFs.


Understanding the impact of 'wish-granting' interventions on the health and well-being of children with life-threatening health conditions and their families: A systematic review.
This review aimed to explore how wish-granting interventions impact on the health and well-being of children with life-threatening health conditions and their families, using any study design. Six electronic databases (Medline; PsycINFO; CINAHL; Embase; AMED and HMIC) were systematically searched to identify eligible research articles. Studies were critically appraised using a Mixed Methods Appraisal Tool. Findings were synthesized narratively. 10 papers were included, reporting studies conducted across five countries, published from 2007 to 2019. Study designs were diverse (four quantitative; two qualitative and four mixed method). Results indicated improvements to physical and mental health, quality of life, social well-being, resilience and coping for wish children, parents and siblings. In conclusion, wish-granting interventions can positively impact health and therefore should not be discouraged; however, more research is needed to define and quantify the impact of wish fulfilment and to understand how it can be maximized.


Comparison of Associations with Different Macular Inner Retinal Thickness Parameters in a Large Cohort: The UK Biobank.
To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell-inner plexiform layer (GCIPL) thicknesses in a large cohort. Cross-sectional study. We included 42 044 participants in the UK Biobank. The mean age was 56 years. Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc. Thicknesses of mRNFL, GCC, and GCIPL. We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: -0.46 μm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61-0.30]; P = 1.1×10-8), greater social deprivation (most significant for GCIPL: -0.28 μm for most deprived quartile compared with least deprived quartile [95% CI, -0.42 to -0.14]; P = 6.6×10-5), lower educational attainment (most significant for mRNFL: -0.36 μm for less than O level compared with degree level [95% CI, -0.45 to 0.26]; P = 2.3×10-14), and nonwhite ethnicity (most significant for mRNFL comparing blacks with whites: -1.65 μm [95% CI, -1.86 to -1.43]; P = 2.4×10-50). Corneal-compensated intraocular pressure was associated most significantly with GCIPL (-0.04 μm/mmHg [95% CI, -0.05 to -0.03]; P = 4.0×10-10) and was not associated significantly with mRNFL (0.00 μm/mmHg [95% CI, -0.01 to 0.01]; P = 0.77). The variables examined explained a greater proportion of the variance of GCIPL (11%) than GCC (6%) or mRNFL (7%). The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma.


[Targeting the skin - erythema multiforme in dogs and cats].
This review article will describe the complex nature of erythema multiforme in dogs and cats. The disease pattern will be illustrated in terms of etiology, pathogenesis, clinical signs, diagnostics and therapy. Erythema multiforme is a rare, immune-mediated skin disorder with an acute specific reaction pattern of skin and mucous membranes against different underlying causes. Reported triggering factors include drugs, food ingredients and neoplasias, but viral or bacterial infections and vaccine reactions were also identified. In over 20% of the cases the cause cannot be identified. The German Shepherd dog and Pembroke Welsh Corgi seem to be predisposed. Erythematous macules, slightly elevated and peripherally spreading papules as well as circular to arciform patterns were described frequently in the dog. Wheals, plaques, vesicles and bullae that develop into ulcers, are also seen. Frequently affected areas in the dog are the ventrum, mucocutaneous junctions, mouth, pinnae and foot pads. Histopathological findings include single cell necrosis in all layers of the epidermis with lymphocytic satellitosis and a cell-poor interface dermatitis. Elimination of the causative factors and concurrent symptomatic therapy are recommended. The prognosis varies from guarded to fair, depending on the underlying cause, presenting clinical signs and response to therapy.


[The radiation therapy of bladder cancer in a regimen of nontraditional fractionation with local radiomodification by metronidazole].
The authors presented short-term and immediate results of radiation therapy of bladder cancer by a conventional method and optimized program, combining accelerated hyperfractionation and local radiomodification with metronidazole. A variant, proposed by the authors, included the use of a single focal dose of 1.4 Gy twice a day with a 4-hour interruption up to a total dose of 39.2 Gy. It was followed by a dose of 6 Gy once a week with preliminary administration of 2 g of metronidazole in 30-40 ml of 50 per cent dimexide solution in the bladder. A total of 2 large fractions of irradiation combined with metronidazole were used. This method was used for the treatment of 89 cancer patients. Better local control and survival in anemic patients with poorly differentiated cancer were observed.


Nucleus accumbens dopamine release reflects Bayesian inference during instrumental learning.
Dopamine release in the nucleus accumbens has been hypothesized to signal reward prediction error, the difference between observed and predicted reward, suggesting a biological implementation for reinforcement learning. Rigorous tests of this hypothesis require assumptions about how the brain maps sensory signals to reward predictions, yet this mapping is still poorly understood. In particular, the mapping is non-trivial when sensory signals provide ambiguous information about the hidden state of the environment. Previous work using classical conditioning tasks has suggested that reward predictions are generated conditional on probabilistic beliefs about the hidden state, such that dopamine implicitly reflects these beliefs. Here we test this hypothesis in the context of an instrumental task (a two-armed bandit), where the hidden state switches repeatedly. We measured choice behavior and recorded dLight signals reflecting dopamine release in the nucleus accumbens core. Model comparison based on the behavioral data favored models that used Bayesian updating of probabilistic beliefs. These same models also quantitatively matched the dopamine measurements better than non-Bayesian alternatives. We conclude that probabilistic belief computation plays a fundamental role in instrumental performance and associated mesolimbic dopamine signaling.


Laser-induced chorioretinal venous anastomosis for nonischemic central or branch retinal vein occlusion.
To establish a communication between an obstructed retinal vein and the choroid by means of laser in eyes with nonischemic central or branch vein occlusion. Retrospective review identified eyes with nonischemic central or branch vein occlusion, and with decreasing or persistently decreased visual acuity of 20/100 or worse for 4 months or more before treatment, that received 1 or more sessions of laser photocoagulation to create a chorioretinal anastomosis. Of 24 eyes with central vein occlusion, an anastomosis formed in 9 (38%) within 2 months after treatment, with visual improvement of 6 or more lines in 2 (8%) of 24 eyes, 1 to 3 lines in 5 (21%), and no improvement in 2 (8%). Of 6 eyes with branch vein occlusion, an anastomosis formed in 3 (50%) within 2 months after treatment, with visual improvement of 1 to 3 lines in 2 (33%) of 6 and no improvement in 1 (16%). No permanent, vision-limiting complications occurred during a mean follow-up of 13 months after the first treatment session or 8 months after the last session. Laser photocoagulation of a retinal vein and Bruch's membrane may create a chorioretinal anastomosis in some eyes with a nonischemic vein occlusion. Progression to an ischemic status may possibly be prevented with successful anastomosis formation. Marked visual improvement may occur. Treatment techniques to create reliably an anastomosis with subsequent visual improvement, while minimizing potential complications, continue to evolve.


Green light: gross primary production influences seasonal stream N export by controlling fine-scale N dynamics.
Monitoring nutrient concentrations at fine-scale temporal resolution contributes to a better understanding of nutrient cycling in stream ecosystems. However, the mechanisms underlying fine-scale nutrient dynamics and its implications for budget catchent fluxes are still poorly understood. To gain understanding of patterns and controls of fine-scale stream nitrogen (N) dynamics and to assess how they affect hydrological N fluxes, we explored diel variation in stream nitrate (NO3-) concentration along a headwater stream with increasing riparian area and channel width. At the downstream site, the highest day-night variations occurred in early spring, when stream NO3- concentrations were 13% higher at night than at daytime. Such day-night variations were strongly related to daily light inputs (R2 = 0.74) and gross primary production (GPP; R2 = 0.74), and they showed an excellent fit with day-night NO- variations predicted from GPP (R2 = 0.85). These results suggest that diel fluctuations in stream NO3- concentration were mainly driven by photoautotrophic N uptake. Terrestrial influences were discarded because no simultaneous diel variations in stream discharge, riparian groundwater level, or riparian solute concentration were observed. In contrast to the downstream site, no diel variations in NO3- concentration occurred at the upstream site, likely because water temperature was colder (10 degrees C vs. 12 degrees C) and light availability was lower (4 vs. 9 mol x m(-2) x d(-1)). Although daily GPP was between 10- and 100-fold lower than daily respiration, photoautotrophic N uptake contributed to a 10% reduction in spring NO3- loads at the downstream site. Our study clearly shows that the activity of photoautotrophs can substantially change over time and along the stream continuum in response to key environmental drivers such as light and temperature, and further, that its capacity to regulate diel and seasonal N fluxes can be important even in low-productivity streams.


Bracing following correction of idiopathic clubfoot using the Ponseti method.
The Ponseti method for the management of idiopathic clubfoot has recently experienced a rise in popularity, with several centers reporting excellent outcomes. The challenge in achieving a successful outcome with this method lies not in correcting deformity but in preventing relapse. The most common cause of relapse is failure to adhere to the prescribed postcorrective bracing regimen. Socioeconomic status, cultural factors, and physician-parent communication may influence parental compliance with bracing. New, more user-friendly braces have been introduced in the hope of improving the rate of compliance. Strategies that may be helpful in promoting adherence include educating the family at the outset about the importance of bracing, encouraging calls and visits to discuss problems, providing clear written instructions, avoiding or promptly addressing skin problems, and refraining from criticism of the family when noncompliance is evident. A strong physician-family partnership and consideration of underlying cognitive, socioeconomic, and cultural issues may lead to improved adherence to postcorrective bracing protocols and better patient outcomes.


A Duty to Describe: Better the Devil You Know Than the Devil You Don't.
Although many researchers have discussed replication as a means to facilitate self-correcting science, in this article, we identify meta-analyses and evaluating the validity of correlational and causal inferences as additional processes crucial to self-correction. We argue that researchers have a duty to describe sampling decisions they make; without such descriptions, self-correction becomes difficult, if not impossible. We developed the Replicability and Meta-Analytic Suitability Inventory (RAMSI) to evaluate the descriptive adequacy of a sample of studies taken from current psychological literature. Authors described only about 30% of the sampling decisions necessary for self-correcting science. We suggest that a modified RAMSI can be used by authors to guide their written reports and by reviewers to inform editorial recommendations. Finally, we claim that when researchers do not describe their sampling decisions, both readers and reviewers may assume that those decisions do not matter to the outcome of the study, do not affect inferences made from the research findings, do not inhibit inclusion in meta-analyses, and do not inhibit replicability of the study. If these assumptions are in error, as they often are, and the neglected decisions are relevant, then the neglect may create a good deal of mischief in the field.


Use of intermediate focus for grazing incidence small and wide angle x-ray scattering experiments at the beamline P03 of PETRA III, DESY.
We describe the new experimental possibilities of the micro- and nanofocus X-ray scattering beamline P03 of the synchrotron source PETRA III at DESY, Hamburg (Germany), which arise from experiments with smaller beam sizes in the micrometer range. This beamline has been upgraded recently to perform new kinds of experiments. The use of an intermediate focus allows for reducing the beam size of microfocused hard X-rays while preserving a large working distance between the focusing elements and the focus position. For the first time, this well-known methodology has been employed to grazing incidence small- and wide-angle X-ray scattering (GISAXS/GIWAXS). As examples, we highlight the applications to in situ studies using microfluidic devices in GISAXS geometry as well as the investigation of the crystallinity of thin films in GIWAXS geometry.


Sheep Model for Uterine Transplantation: The Best Option Before Starting a Human Program.
This study reports the first four cases of a uterine transplant procedure conducted in sheep in Latin America. The aim of this study was to evaluate the success of uterine transplantation in sheep. The study was conducted at Laboratory of Medical Investigation 37 (LIM 37) at the University of São Paulo School of Medicine. Four healthy mature ewes weighing 40-60 kg were used as both the donor and recipient for a transplant within the same animal (auto-transplant). Institutional guidelines for the care of experimental animals were followed. The first two cases of auto-transplant were performed to standardize the technique. After complete uterine mobilization and isolation of the blood supply, the unilateral vascular pedicle was sectioned and anastomosed on the external iliac vessels. After standardization, the protocol was implemented. Procurement surgery was performed without complications or bleeding. After isolation of uterine arteries and veins as well as full mobilization of the uterus, ligation of the distal portion of the internal iliac vessels was performed with subsequent division and end-to-side anastomosis of the external iliac vessels. After vaginal anastomosis, the final case presented with arterial thrombosis in the left uterine artery. The left uterine artery anastomosis was re-opened and flushed with saline solution to remove the clot from the artery lumen. Anastomosis was repeated with restoration of blood flow for a few minutes before another uterine artery thrombosis appeared on the same side. All four animals were alive after the surgical procedure and were euthanized after the experimental period. We describe the success of four uterine auto-transplants in sheep models.


Thiamine suppresses thermal hyperalgesia, inhibits hyperexcitability, and lessens alterations of sodium currents in injured, dorsal root ganglion neurons in rats.
B vitamins can effectively attenuate inflammatory and neuropathic pain in experimental animals, while their efficacy in treating clinical pain syndromes remains unclear. To understand possible mechanisms underlying B vitamin-induced analgesia and provide further evidence that may support the clinical utility of B vitamins in chronic pain treatment, this study investigated effects of thiamine (B1) on the excitability and Na currents of dorsal root ganglion (DRG) neurons that have been altered by nerve injury. Nerve injury was mimicked by chronic compression of DRG in rats. Neuropathic pain was evidenced by the presence of thermal hyperalgesia. Intracellular and patch-clamp recordings were made in vitro from intact and dissociated DRG neurons, respectively. (1) In vivo intraperitoneal administration of B1 (66 mg/kg/day, 10-14 doses) significantly inhibited DRG compression-induced neural hyperexcitability, in addition to suppressing thermal hyperalgesia. (2) In vitro perfusion of B1 (0.1, 1 and 10 mM) resulted in a dose-dependent inhibition of DRG neuron hyperexcitability. In addition, the DRG neurons exhibited size-dependent sensitivity to B1 treatment, i.e., the small and the medium-sized neurons, compared to the large neurons, were significantly more sensitive. (3) Both in vitro (1 mM) and in vivo application of B1 significantly reversed DRG compression-induced down-regulation of tetrodotoxin-resistant but not tetrodotoxin-sensitive Na current density in the small neurons. B1 at 1 mM also reversed the compression-induced hyperpolarizing shift of the inactivation curve of the tetrodotoxin-resistant currents and the upregulated ramp currents in small DRG neurons. Thiamine can reduce hyperexcitability and lessen alterations of Na currents in injured DRG neurons, in addition to suppressing thermal hyperalgesia.


Effects of therapeutic concentrations of diphenylhydantoin on transmembrane potentials of normal and depressed Purkinje fibers.
Standard intracellular microelectrode techniques were used to study canine Purkinje fibers (PF) which had been superfused with blood or Tyrode's solution to determine the cardiac cellular electrophysiologic changes induced by antiarrhythmic concentrations of diphenylhydantoin (DPH). Some PF were normal whereas others were depressed by stretch, exposure to ouabain (125 mug/1) or superfusion with a solution in which all Na+ was replaced by tetraethylammonium. For normal fibers, therapeutic concentrations of DPH (DPH) induced slight decreases in action potential (AP) amplitude, maximum upstroke velocity of phase O (Vmax) and membrane responsiveness and somewhat greater decreases in AP duration. For fibers moderately depressed by ouabain or stretch, with reduced AP amplitude, maximum diastolic potential and Vmax, therapeutic [DPH] increased these variables. Fibers markedly depressed by Na-free solution or stretch developed slow response AP. The amplitude and Vmax of the AP were decreased by therapeutic [DPH]. Therapeutic [DPH] also suppressed automaticity and ouabain-induced delayed afterdepolarizations. Our studies suggest that the slight depression of normal PF AP characteristics induced by therapeutic [DPH] probably is of little significance with respect to antiarrhythmic effect. In contrast, both the improvement of AP characteristics of moderately depressed fibers and further depression of severely depressed fibers caused by [DPH] might modify arrhythmias. Effects of DPH on automaticity and delayed afterdepolarizations also would contribute to its antiarrhythmic effect.


Perspectives on tolerability and reasonableness.
Judgements on tolerability and reasonableness are central to the optimisation of protection. There are currently several international developments regarding these key considerations which will contribute to the review and evolution of the system of radiological protection. The IRPA15 International Congress brought together the principal issues currently under discussion, and the outcome of these discussions is presented.


Effects of dopamine D1 and D2 receptor agonists and antagonists on bombesin-induced behaviors.
Central administration of bombesin elicits excessive grooming and locomotor activity in rats. This grooming activity is one characterised by vigorous scratching of the face, nape and body flanks. Pretreatment with the D1 receptor antagonist SCH 23390 inhibited the expression of bombesin-induced activity with grooming being more inhibited than locomotion. Blockade of D2 receptors with eticlopride significantly attenuated the behavioral responses to bombesin. When SCH 23390 and eticlopride were administered concurrently, it was apparent that D1 blockade had a greater effect on grooming and D2 blockade a larger effect on locomotion. Stimulation of D1 receptors by SKF 38393 elicited non-stereotyped locomotor activity and a form of grooming behavior characterised by vigorous washing of the face and ventral body surfaces. Co-administration of bombesin and SKF 38393 resulted in a form of grooming which resembled that elicited by SKF 38393 alone. The specific D2 agonist PPHT elicited a form of locomotion characterised by a downward oriented head posture and slow ambulatory activity around the cage perimeter. Co-administration of PPHT and bombesin resulted in a complete suppression of bombesin-induced behaviors and was largely indistinguishable from activity observed under PPHT alone conditions. These data implicate both D1 and D2 receptor based mechanisms in the modulation/mediation of the behavioral effects of bombesin. Part of the bombesin-induced behavioral effects may be explained by (indirect) activation of (a) dopamine system(s).