Testing the Sarcocystis neurona vaccine using an equine protozoal myeloencephalitis challenge model.
Equine protozoal myeloencephalitis (EPM) is an important equine neurologic disorder, and treatments for the disease are often unrewarding. Prevention of the disease is the most important aspect for EPM, and a killed vaccine was previously developed for just that purpose. Evaluation of the vaccine had been hampered by lack of post vaccination challenge. The purpose of this study was to determine if the vaccine could prevent development of clinical signs after challenge with Sarcocystis neurona sporocysts in an equine challenge model. Seventy horses that were negative for antibodies to S. neurona and were neurologically normal were randomly assigned to vaccine or placebo groups and divided into short-term duration of immunity (study #1) and long-term duration of immunity (study #2) studies. S. neurona sporocysts used for the challenge were generated in the opossum/raccoon cycle isolate SN 37-R. Study #1 horses received an initial vaccination and a booster, and were challenged 34days post second vaccination. Study #2 horses received a vaccination and two boosters and were challenged 139days post third vaccination. All horses in study #1 developed neurologic signs (n=30) and there was no difference between the vaccinates and controls (P=0.7683). All but four horses in study #2 developed detectable neurologic deficits. The neurologic signs, although not statistically significant, were worse in the vaccinated horses (P=0.1559). In these two studies, vaccination with the S. neurona vaccine failed to prevent development of clinical neurologic deficits.


The economics of information exchange: Medicaid in Wisconsin.
In Medicaid, as in all third-party insurance, there are significant costs for information exchange between providers of services and the State (or other insurer), which reimburses those providers. On the basis of a study of Medicaid in Wisconsin, this article indicates that appreciable costs are incurred owing to deficiencies in information exchange between these parties. It is proposed that the costs of automated interventions, which could improve information exchange, be compared with the existing costs of the present system of information exchange.


Correlation between age-related macular degeneration and pseudoexfoliation syndrome in the population of Crete (Greece).
To evaluate the epidemiological correlation between age-related macular degeneration and pseudoexfoliation syndrome in the inhabitants of the island of Crete (Greece). A total of 777 persons (315 men and 462 women, aged 40-99 years), representing a randomized sample (1.43%) of the Cretan population, underwent slitlamp and fundus examinations according to protocol. The results were statistically analyzed. The prevalence of pseudoexfoliation was 16.1% (21.3% in men and 12.6% in women) and that of maculopathy, 7.9% (11.7% in men and 5.2% in women). The conditions were significantly correlated with each other (P = .002). Also, both displayed a significant direct correlation with age and altitude (for pseudoexfoliation, P<.001 and P = .002 for age and altitude, respectively; for age-related macular degeneration, P<.001 for age and for altitude) and an increase in bilateral incidence with progressing age. The observed prevalences of pseudoexfoliation and maculopathy were lower than those reported in the mainland of Greece and other Mediterranean regions. The correlation between age-related macular degeneration and pseudoexfoliation syndrome may be explained by the relationship of each disease with age and altitude.


Assessment of rehabilitation potential in patients with vascular dysfunction caused by undifferentiated connective tissue dysplasia.
Degradation of collagen, inherent to undifferentiated connective tissue dysplasia (UCTD) syndrome, also influences the changes in the structure of vascular walls. This contributes to the development of configured vascular anomalies, which are an independent predictor of vascular accident risk. Such diversity of UCTD manifestations requires development of prognostic criteria for rehabilitation potential, correction of which may contribute to recovery process in case of development of vascular catastrophe. Study aim is to evaluate the rehabilitation potential in patients with vascular dysfunction and underlying UCTD. The study involved 150 male patients with confirmed diagnosis of UCTD (average age - 26.4 ± 0.6 years). All patients had a complex clinical and instrumental examination. Phenotypic and UCTD visceral stigmas, UCTD biochemical markers were analyzed, followed by statistical processing of the results by method of variotional statistics. We revealed the high degree of direct correlation between the presence of vascular dysfunction and myxomatous degeneration of the mitral valve (r = + 0.76, p.


Nitric oxide preserves the glomerular protein permeability barrier by antagonizing superoxide.
The interaction of nitric oxide with superoxide (O2-) is a major O2- scavenging mechanism that can minimize O2 (-)-mediated oxidative stress. Glomeruli produce both nitric oxide and O2- and generation of both radicals is increased in various forms of glomerular disease. O2- increases glomerular capillary permeability to albumin (P(alb)). The present studies tested the hypothesis that nitric oxide opposes this effect, thereby preserving the glomerular protein permeability barrier. P(alb) was determined in isolated rat glomeruli by measuring the change in glomerular volume in response to an experimental oncotic gradient. Changes in P(alb) in response to O2- generated by tumor necrosis factor-alpha (TNF-alpha) or xanthine/xanthine oxidase (X/XO) was assessed under conditions of nitric oxide depletion and repletion. Incubation of rat glomeruli with the nitric oxide synthase (NOS) inhibitor L-N(G)-monomethyl arginine (L-NMMA) increased P(alb.) This effect was reversed by the nitric oxide donor diethylenetriamine NONOate (DETA-NONOate) and by the superoxide dismutase (SOD) mimetic Tempol. O2- generated after incubation with TNF-alpha or X/XO increased P(alb). This effect was blocked by DETA-NONOate. We demonstrate that nitric oxide protects the glomerular filtration barrier from injury caused by O2- and suggest that inhibition of nitric oxide synthesis could enhance O2(-)-mediated oxidative injury under pathologic conditions.


Arachidonate metabolites and vasospasm after subarachnoid haemorrhage.
A wide literature exists about the pathogenesis of cerebral arterial spasm following subarachnoid haemorrhage: several compounds have been identified in human cerebrospinal fluid as possible vasoactive agents involved in the biochemical mechanism of vasospasm onset. Many experimental evidences exist for a major involvement of arachidonate metabolites. The present work represents a review of experimental data supporting the hypothesis of cerebral arterial spasm as a result of an imbalanced vascular regulatory mechanism involving arachidonate metabolites. The authors have also monitored, in 25 cases of aneurysmal subarachnoid haemorrhage, lumbar and cisternal CSF levels of prostacyclin and PGD2, as representative of vasodilating and, respectively, vasoconstrictor compounds. In all cases CSF arachidonate metabolite levels after SAH were significantly higher than in control cases. Ten patients presented with symptomatic vasospasm: lumbar CSF PGD2 levels show fluctuations with superimposed peaks related to the neurological deterioration due to vasospasm, while lumbar CSF prostacyclin concentration-trend suggest a decreasing synthesis. In 15 patients presenting without vasospasm, lumbar CSF concentration of arachidonate metabolites are in a 'steady-state'. These data confirm the existence of an imbalanced biochemical situation promoting vasospasm, markedly in cisterns near to the ruptured aneurysmal wall. The evaluation of cisternal CSF levels of arachidonate metabolites supports the hypothesis of the clotting phenomenon around the ruptured aneurysm as an important predictive pattern of vasospasm, as shown in CT findings.


Primary gastrointestinal diffuse large B cell lymphoma presenting with cold agglutinin disease.
Cold agglutinin disease (CAD) is an autoimmune hemolytic anemia (AIHA) generally caused by IgM autoantibodies which exhibit maximal reactivity at 4°C. CAD can be idiopathic or secondary to some diseases and/or conditions. Only a minority of cases of secondary AIHA in non-Hodgkin's lymphoma (NHL) are associated with cold antibodies. Diffuse large B cell lymphoma (DLBCL) is the most common subtype of NHLs with a proportion of nearly 30% of all adult cases. 40% of patients with DLBCL have an extranodal disease or at least disease initially confined to extranodal sites. The most common extranodal site is the gastrointestinal tract. We present a patient with primary gastrointestinal DLBCL who presented with CAD and was treated with a CHOP-Rituximab regimen.


Interaction between long-term potentiation and depression in CA1 synapses: temporal constrains, functional compartmentalization and protein synthesis.
Information arriving at a neuron via anatomically defined pathways undergoes spatial and temporal encoding. A proposed mechanism by which temporally and spatially segregated information is encoded at the cellular level is based on the interactive properties of synapses located within and across functional dendritic compartments. We examined cooperative and interfering interactions between long-term synaptic potentiation (LTP) and depression (LTD), two forms of synaptic plasticity thought to be key in the encoding of information in the brain. Two approaches were used in CA1 pyramidal neurons of the mouse hippocampus: (1) induction of LTP and LTD in two separate synaptic pathways within the same apical dendritic compartment and across the basal and apical dendritic compartments; (2) induction of LTP and LTD separated by various time intervals (0-90 min). Expression of LTP/LTD interactions was spatially and temporally regulated. While they were largely restricted within the same dendritic compartment (compartmentalized), the nature of the interaction (cooperation or interference) depended on the time interval between inductions. New protein synthesis was found to regulate the expression of the LTP/LTD interference. We speculate that mechanisms for compartmentalization and protein synthesis confer the spatial and temporal modulation by which neurons encode multiplex information in plastic synapses.


Traumatic hemorrhage within a cerebellar dermoid cyst.
Intracranial dermoid cysts with hemorrhage are fairly rare. Herein, we reported a 28-year-old female patient with a cerebellar dermoid cyst, which was found accidently on neuro-imaging after head trauma. MR scanning revealed that the lesion was located within the cerebellar vermis and was measured 3.5cm×3.9cm×3.0cm, with hyper-intensity on T1WI and hypo-intensity on T2WI. However, on CT imaging, it showed hyper-dense signals. It was removed completely via midline sub-occipital approach under surgical microscope. Histological examination proved it was a dermoid cyst with internal hemorrhage. In combination with literature review, we discussed the factors that might be responsible for the hemorrhage within dermoid cysts.


Mosquitoes (Diptera: Culicidae) in relation to the risk of disease transmission in El Ismailia Governorate, Egypt.
Mosquito were surveyed (Nov. 2009 - March 2010) in El Ismailia Governorate. Nine species were reported: Culex pipiens, Cx. perexiguus, Cx. antennatus, Anopheles tenebrosus, An. pharoensis, An. multicolor, Ochlerotatus detritus, Oc. caspius and Culiseta longiareolata. Culex pipiens was the predominant species (ca. 87% larvae and 57% adults). For the 3 common species, Cx. pipiens, Cx. perexiguus, and Cx. antennatus the following were examined: (1) the type and characteristics (temperature and pH) of the breeding habitats and their relation to the larval density and (2) the relation of adult indoor density to the indoor and outdoor temperature and RH. The abundance of mosquito vectors in El Ismailia with its old history of vector transmitted diseases contributes to the risk of mosquito borne disease transmission in this area. This would assist in the control activities.


Incidence and Antiseizure Medications of Post-stroke Epilepsy in Umbria: A Population-Based Study Using Healthcare Administrative Databases.
Introduction: Post-stroke epilepsy (PSE) requires long-term treatment with antiseizure medications (ASMs). However, epidemiology of PSE and long-term compliance with ASM in this population are still unclear. Here we report, through population-level healthcare administrative data, incidence, risk factors, ASM choice, and ASM switch over long-term follow-up. Materials and Methods: This is a population-based retrospective study using Umbria healthcare administrative database. Population consisted of all patients with acute stroke, either ischaemic or hemorrhagic, between 2013 and 2018. ICD-9-CM codes were implemented to identify people with stroke, while PSE was adjudicated according to previously validated algorithm, such as EEG and ≥1 ASM 7 days after stroke. Results: Overall, among 11,093 incident cases of acute stroke (75.9% ischemic), 275 subjects presented PSE, for a cumulative incidence of 2.5%. Patients with PSE were younger (64 vs. 76 years), more frequently presented with hemorrhagic stroke, and had longer hospital stay (15.5 vs. 11.2 days) compared with patients without PSE. Multivariable Cox proportional hazards models confirmed that PSE associated with hemorrhagic stroke, younger age, and longer duration of hospital stay. Levetiracetam was the most prescribed ASM (55.3%), followed by valproate and oxcarbazepine. Almost 30% of patients prescribed with these ASMs switched treatment during follow-up, mostly toward non-enzyme-inducing ASMs. About 12% of patients was prescribed ASM polytherapy over follow-up. Conclusions: Post-stroke epilepsy is associated with hemorrhagic stroke, younger age, and longer hospital stay. First ASM is switched every one in three patients, suggesting the need for treatment tailoring in line with secondary prevention.


Association between acute and chronic life events on acute coronary syndrome: a case-control study.
Some studies have shown that acute and chronic psychological stressors are associated with acute coronary syndromes (ACSs). The aim of the present study was to assess the association between acute and chronic psychological stressors and ACS in an Iranian population. In an age-sex frequency-matched, case-control study, 78 hospitalized patients with ACS as the case group were compared with 146 patients with chronic stable angina (CSA) as the control group. Chronic stable angina was confirmed by positive angiographic findings. Acute stressors were examined through a semistructured interview and the acute life event checklist, regarding stressful events during 48 hours before interview. To assess chronic stress, the occurrence of 46 stressful events in a period of 6 months prior to the interview was examined using the stress inventory questionnaire. The average acute stressor counts were 4.80 (SD, 2.87) and 3.97 (SD, 2.2) in ACS and CSA groups, respectively (P = .028). Chronic stressor counts were 9.91 (SD, 5.86) and 6.58 (SD, 3.16) in case and control groups (<.001), respectively. Odds ratios for acute and chronic stressor counts were 1.14 (95% confidence interval [95% CI], 1.02-1.28) and 1.84 (95% CI, 1.10-1.26), respectively; when the associations were adjusted for traditional risk factors, they become 1.12 (95% CI, 0.99-1.27) and 1.20 (95% CI, 1.10-1.30), respectively. Acute stress did not contribute significantly in the models including chronic stress. Acute stressful events in the recent 48 hours, independent of traditional risk factors, can have a triggering effect on ACS occurrence. Nevertheless, this happens in the context of high chronic stress. In addition, chronic stress count was moderately associated with ACS even when it was adjusted for traditional risk factors (ALEACE study).


Metabolic and Hormonal Profile of Adolescent Girls With Polycystic Ovary Syndrome With Concomitant Autoimmune Thyroiditis.
Both polycystic ovary syndrome (PCOS) and autoimmune thyroiditis (AT) are considered to be among the most common endocrinopathies in young women, and they are classified as diseases that affect many processes in the human body. Their role in the development of metabolic disorders and diseases of the cardiovascular system in adult women is also emphasized. However, there are no data available to assess such risk in the teenage girl population. The aim of the study was to assess the hormonal and metabolic profile of adolescent girls with PCOS, additionally diagnosed with AT, as well as to identify possible risk factors for the coexistence of AT and PCOS. 80 euthyroidic PCOS patients were qualified for the study (chronological age 16.54 ± 1.00 years, BMI 24.60 ± 4.16 kg/m2). Eighteen girls diagnosed with AT were included in the study group and 62 girls without AT-in the control group. Each patient had biochemical and hormonal tests performed. Additionally, to diagnose AT, the level of antibodies against thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG), as well as the image of the thyroid gland on ultrasound examination, were taken into account. Estradiol concentration was significantly higher in the study than in the control group (203.00 ± 217.00 vs. 152.00 ± 78.50 pmol/L, p=0.02). Higher DHEAS concentrations were also observed in the AT group compared with the group without AT (391.28 ± 176.40 vs. 317.93 ± 114.27 µg/dl, p=0.04). Moreover, there was a positive correlation between AT and estradiol concentration (ry=0.27; p=0.04). It was also shown that there is a tendency toward statistical significance for the positive correlation between the positive anti-TPO titer and the glucose concentration at 120 min OGTT (rƴ=0.26; p=0.07) and girls with PCOS and AT had higher glucose levels in 120 min OGTT (115.29±41.70 vs. 98.56±28.02 mg/dl, p=0.08). The study results showed no difference in the metabolic profile between the groups. The high concentration of estradiol found in girls with PCOS and AT may indicate the role of this hormone in the development of the autoimmune process. However, the numbers are small, and more research is needed to confirm our findings.


Effects of Duraflo II heparin-coated cardiopulmonary bypass circuits on the coagulation system, endothelial damage, and cytokine release in patients with cardiac operation employing aprotinin and steroids.
The effects of Duraflo II heparin coated cardiopulmonary bypass circuits, low-dose aprotinin, and steroids on the coagulation system, endothelial damage, and cytokine release were evaluated by comparing those treated with low-dose aprotinin and steroids. Twenty-four adult patients undergoing coronary artery bypass grafting, aortic valve replacement, or valve repair surgery were randomly assigned to 2 groups: either heparin-coated (Duraflo group, n = 12) or noncoated equipment (noncoated group, n = 12) groups. In the Duraflo group, the cardiopulmonary reservoir was also coated with heparin. There were no significant differences in age at the time of operation, aortic cross-clamp time, cardiopulmonary bypass time, and rectal temperature during cardiopulmonary bypass. Standard systemic heparinization was performed. Methylpredonisolone and low-dose aprotinin were given in both groups of patients. Serum XIIa factor, TAT, and IL-6 were significantly higher in the control group than in the Duraflo group during cardiopulmonary bypass (p < 0.01). Serum IL-8 was significantly higher in the control group than in the Duraflo group at 24 h after cardiopulmonary bypass (p < 0.05). No significant difference was found in serum thrombomodulin and TNF-alpha; both were within normal during the study period. These results indicate that the use of Duraflo II heparin coated equipment and a heparin-coated cardiopulmonary reservoir suppressed excess coagulation and inflammatory reaction induced by cardiopulmonary bypass.


ADAMTS-13 regulates platelet adhesion under flow. A new method for differentiation between inherited and acquired thrombotic thrombocytopenic purpura.
ADAMTS-13 cleaves large and ultra-large von Willebrand factor multimers normally secreted by endothelial cells. Severe deficiency of this enzyme leads to thrombotic thrombocytopenic purpura (TTP). We applied the Impact-R system [Cone and plate(let) Analyzer, CPA] to determine optimal conditions for ADAMTS-13 function, to assess it's activity in TTP patients and to distinguish inherited TTP (inTTP) from acquired TTP (acTTP). The role of ADAMTS-13 in platelet adhesion under different conditions was investigated applying recombinant forms of VWF and ADAMTS-13. rVWF was first treated by rADAMTS-13 either in solution or when immobilized on the surface of the well, under static or flow conditions, in the presence or absence of BaCl2. The resulting cleaved VWF fragments were then immobilized and served to assess type 3 von Willebrand disease whole blood platelet adhesion under flow. Maximal effect of the rADAMTS-13 (decrease of platelet adhesion in the absence compared to the presence of BaCl2), was observed when the rVWF was pre-immobilized and the cleavage step took place under flow (85%). Mixing plasma ofTTP patients with normal blood (1:3) yielded a 1.6- to 2-fold increase of platelet adhesion under flow compared to mixing normal plasma with normal blood, at shear rate range of 1,800 - 2,500 s(-1) . Maximal increase of platelet adhesion was observed under 2,050 s(-1) . Under these conditions, the extent of adhesion was similarly higher in patients with inTTP and acTTP versus control [surface coverage (SC) 14.5 +/- 2.8% and 14.6 +/- 2.5% vs.7.4 +/- 1.7%, respectively]. ADAMTS-13 activity measured by collagen-binding test was similarly low (4.2 +/- 3.8% and 3.5 +/- 2.4% vs. 72.2 +/- 8.0%, respectively). An inverse correlation between SC and ADAMTS-13 activity was observed in a patient with inTTP assayed eight times during plasma infusion treatment. Addition of BaCl2 to the mixture of TTP plasma and normal whole blood yielded a decrease in platelet adhesion in inTTP (by 51%) but not in acTTP. The lack of reduction of platelet adhesion in acTTP could presumably be due to the presence of ADAMTS-13 inhibitor in these patients. These results suggest that VWF immobilization and high shear flow yielded optimal conditions for ADAMTS-13 activity, and that introduction of BaCl2 in the Impact-R (CPA) test may be useful for differentiation between inherited and acquired TTP.


Yield analysis of multilayer optical coatings.
Yield is defined as the ratio of the number of devices that satisfy a particular technical specification to the total number of devices produced. For coated optical devices, random layer thickness variations decrease the yield. Variations in refractive index can also affect yields, but in this work we assume that changes in index are not as important as changes in thickness. A graphic method of yield analysis for optical coatings is presented. This method probes the sensitivity of the device performance against thickness variations and translates it into yield figures. Five examples of this analysis are provided including spectral and nonspectral applications.


Socioeconomic impact of acoustic neuroma surgery.
This study aimed to assess the impact of acoustic neuroma (AN) surgery on socioeconomic function. This study was a retrospective postal survey. The study was performed at a tertiary referral center. One hundred thirty late postoperative AN patients were surveyed a minimum of 6 months after surgery (average 39 months). The survey response rate was 65% (130 of 200). These included effect of AN surgery on employability, income, activities of daily living, social involvement, and psychological well-being. When comparing preoperative occupational status with latest follow-up, 2 of 125 (1.6%) became unemployed from their usual occupations. An additional 15 of 125 (12%) retired, attributing their retirement to the effects of the tumor itself (3), an aftermath of surgery (2), and causes unrelated to their AN (10). After AN removal, two formerly unemployed patients became employed. Among those remaining employed, there was no significant impact of surgery on either income or work responsibility. Return to normal activity was gradual: < or = 6 weeks, 31%; < or = 3 month, 64%; and < or = 6 months, 84%. Among activities of daily living, the tasks most often impaired (both before and after tumor removal) were ladder climbing and night driving, whereas dressing and bathing were seldom problematic. Overall, patients reported a minor decline in ability to perform routine daily activities after tumor removal. Social function (contact with friends, community involvement, and participation in sports) changed little after surgery. The incidence of both stress and depression decreased slightly after tumor removal. The economic, social, and psychological impact of AN and its surgical management appears to be relatively minor, with few individuals having life altering consequences.


Elevated Markers of Vascular Remodeling and Arterial Stiffness Are Associated With Neurocognitive Function in Older HIV+ Adults on Suppressive Antiretroviral Therapy.
HIV is associated with elevated markers of vascular remodeling that may contribute to arterial fibrosis and stiffening and changes in pulse pressure (PP). These changes may, in turn, deleteriously affect autoregulation of cerebral blood flow and neurocognitive function. To evaluate these mechanisms, we studied markers of vascular remodeling, PP, and neurocognitive function among older (≥50 years of age) HIV-infected (HIV+, n = 72) and HIV-seronegative (HIV-, n = 36) adults. Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well-validated comprehensive battery. Three plasma biomarkers of vascular remodeling (ie, angiopoietin 2, Tie-2, and vascular endothelial growth factor, VEGF) were collected. HIV+ and HIV- participants had similar levels of plasma angiopoietin 2 (P = 0.48), Tie-2 (P = 0.27), VEGF (P = 0.18), and PP (P = 0.98). In a multivariable regression model, HIV interacted with Tie-2 (β = 0.41, P < 0.01) and VEGF (β = -0.43, P = 0.01) on neurocognitive function, such that lower Tie-2 and higher VEGF values were associated with worse neurocognitive function for HIV+ participants. Greater Tie-2 values were associated with increased PP (r = 0.31, P < 0.01). In turn, PP demonstrated a quadratic association with neurocognitive function (β = -0.33, P = 0.01), such that lower and higher, relative to mean sample, PP values were associated with worse neurocognitive function. These findings indicate that vascular remodeling and altered cerebral blood flow autoregulation contribute to neurocognitive function. Furthermore, HIV moderates the association between vascular remodeling and neurocognitive function but not the association between PP and neurocognitive function.


Ultra-High-Dose-Rate FLASH Irradiation Limits Reactive Gliosis in the Brain.
Encephalic radiation therapy delivered at a conventional dose rate (CONV, 0.1-2.0 Gy/min) elicits a variety of temporally distinct damage signatures that invariably involve persistent indications of neuroinflammation. Past work has shown an involvement of both the innate and adaptive immune systems in modulating the central nervous system (CNS) radiation injury response, where elevations in astrogliosis, microgliosis and cytokine signaling define a complex pattern of normal tissue toxicities that never completely resolve. These side effects constitute a major limitation in the management of CNS malignancies in both adult and pediatric patients. The advent of a novel ultra-high dose-rate irradiation modality termed FLASH radiotherapy (FLASH-RT, instantaneous dose rates ≥106 Gy/s; 10 Gy delivered in 1-10 pulses of 1.8 µs) has been reported to minimize a range of normal tissue toxicities typically concurrent with CONV exposures, an effect that has been coined the "FLASH effect." Since the FLASH effect has now been found to significantly limit persistent inflammatory signatures in the brain, we sought to further elucidate whether changes in astrogliosis might account for the differential dose-rate response of the irradiated brain. Here we report that markers selected for activated astrogliosis and immune signaling in the brain (glial fibrillary acidic protein, GFAP; toll-like receptor 4, TLR4) are expressed at reduced levels after FLASH irradiation compared to CONV-irradiated animals. Interestingly, while FLASH-RT did not induce astrogliosis and TLR4, the expression level of complement C1q and C3 were found to be elevated in both FLASH and CONV irradiation modalities compared to the control. Although functional outcomes in the CNS remain to be cross-validated in response to the specific changes in protein expression reported, the data provide compelling evidence that distinguishes the dose-rate response of normal tissue injury in the irradiated brain.


[A study to compare formal duties of medical directors of Italian public hospitals with actual activities performer].
It is difficult to identify, from a regulatory point of view, the actual competencies of medical directors of public hospitals in Italy. A questionnaire survey was therefore conducted to identify which are the activities actually performed by this professional. One hundred twenty local health authorities participated in the survey. Findings reveal that many activities conducted by the hospital medical director, such a mediation with the local health authorities, are not formally recognized and that the medical director actually conducts more complex activities than those formally pertaining to his role.


Development and assessment of the Canadian personal load carriage system using objective biomechanical measures.
The Defence Research and Development Canada--Toronto managed a collaborative team of designers, biomechanists, ergonomists and military stakeholders in the development of a new personal load carriage (LC) system for the Canadian Forces. Ergonomics design principles using objective measurement tools and user-centred feedback from soldiers were considered essential to system development. The purpose of this study was to provide a detailed report of contributions by biomechanical testing to the final design of the final Canadian LC system. The Load Carriage Simulator and Compliance Tester were used to test design iterations of: three fragmentation vests, seven tactical vests and three iterations of the backpack. Test data were compared to a data pool of seventeen previously tested systems. Results indicated that the objective measures helped the design team by: (1) quantifying and understanding the consequences of various design changes; (2) predicting soldiers' responses to design changes in skin contact pressure, force and relative motion; (3) objectively comparing design iterations to other systems; and (4) providing information quickly so that ideas and recommendations could be incorporated into the next design iteration. It was concluded that objective assessments added valuable information not easily interpreted from human trials. However, objective assessments cannot replace human trials for feedback on functionality and features.


Reduction of mRNA export unmasks different tissue sensitivities to low mRNA levels during Caenorhabditis elegans development.
Animal development requires the execution of specific transcriptional programs in different sets of cells to build tissues and functional organs. Transcripts are exported from the nucleus to the cytoplasm where they are translated into proteins that, ultimately, carry out the cellular functions. Here we show that in Caenorhabditis elegans, reduction of mRNA export strongly affects epithelial morphogenesis and germline proliferation while other tissues remain relatively unaffected. Epithelialization and gamete formation demand a large number of transcripts in the cytoplasm for the duration of these processes. In addition, our findings highlight the existence of a regulatory feedback mechanism that activates gene expression in response to low levels of cytoplasmic mRNA. We expand the genetic characterization of nuclear export factor NXF-1 to other members of the mRNA export pathway to model mRNA export and recycling of NXF-1 back to the nucleus. Our model explains how mutations in genes involved in general processes, such as mRNA export, may result in tissue-specific developmental phenotypes.


The increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood during vagal afferents stimulation or after angiotensin II infusion.
It has previously been demonstrated that the cardiodepressant activity is present in the bovine hypothalamic extract and in the fluid incubating the posterior pituitary lobe "in situ". The present study was an attempt to reveal if the cardiodepressant factor and vasopressin were simultaneously released from the pituitary into blood. The samples of venous blood flowing from the sella turcica and, for comparison, from the posterior paw were collected in anaesthetized rats. Blood from the sella turcica was collected with a fine cannula inserted into the internal maxillary vein. The concentration of vasopressin in blood plasma was determined by radioimmunoassay and cardiodepressant activity--using a biological test on a spontaneously discharged pacemaker tissue of the right auricle of the right heart atrium. Stimulation of the central ends of the cut vagus nerves or intra-arterial infusion of angiotensin II simultaneously caused an increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood. The cardiodepressant activity and vasopressin concentration was also enhanced to some degree in blood outflowing from the posterior paw. Present results indicate that both vasopressin and the cardiodepressant factor are released into blood from the posterior pituitary lobe.


[Effect of "Tongyuan" acupuncture treatment on success rate of extubation in stroke patients undergoing tracheotomy].
To observe the impact of "Tongyuan" (regulating the Governor Vessel to tranquilize mental activities, conducting qi back to its origin) acupuncture treatment on cough reflex, pulmonary infection and swallowing function in stroke patients undergoing tracheotomy. Seventy-four cerebral stroke patients with tracheo-tomy were randomly allocated to scalp acupuncture and "Tongyuan" acupuncture groups (n=37 in each group). All the patients of the two groups received basic treatment, including treatment of primary diseases, routine nursing, respiratory muscle training, physical therapy, acupuncture of Chize (LU5), Quchi (LI11), Hegu (LI4), Weizhong (BL40), Zusanli (ST36). In addition, for patients of the scalp acupuncture group, the middle 2/5 of Dingnieqianxiexian (MS6), the middle 2/5 of Dingniehouxiexian (MS7) and Dingpangerxian (MS9) on the contralateral side of lesions were punctured with filiform needles. For patients of the "Tongyuan" acupuncture group, Baihui (GV20), Zhongwan (GV12), Guanyuan (CV4), Qihai (CV6), Tianshu (ST25), Feishu (BL13), Pishu (BL20) were needled. The treatment in both groups lasted 30 minutes each time, once daily, 6 times a week for 4 weeks. The cough reflex grading score (CRGS, assessed according to cough, independent expectoration, sputum suction), clinical pulmonary infection score (CPIS, assessed according to the body temperature, white blood cell count, airway secretion in 24 h, PaO2/FiO2, infiltration status, cultured pathogenic bacteria), and swallowing function were evaluated by a researcher who was blinded to the grouping and treatment procedures. The success rate of extubation was calculated in a week at the end of treatments. After the treatment, the CRGS and CPIS of both groups were apparently decreased in comparison with their own pre-treatment (P<0.05), suggesting an improvement of the cough reflex and pulmonary infection. Regarding the swallowing function, of the two 37 cases in the scalp acupuncture and "Tongyuan" acupuncture groups, 9(24.3%) and 19(51.4%) experienced marked improvement, 12(32.5%)and 14(37.8%) were effective, and 16(43.2%) and 4(10.8%)failed in the treatment, with the effective rate being 56.8% and 89.2%, respectively. In regard to the successful extubation, of the two 37 cases in the scalp acupuncture and "Tongyuan" acupuncture groups, 5(13.5%) and 11(29.8%)had a marked improvement, 10(27.0%)and 18(48.6%)were effective, and 22(59.5%)and 8(21.6%)failed, with the effective rate being 40.5% and 78.4%, respectively. The therapeutic effect of "Tongyuan" acupuncture was significantly superior to that of scalp acupuncture in decreasing CRGS and CPIS, and in improving the swallowing function and raising the rate of successful extubation (P<0.05). "Tongyuan" acupuncture treatment can improve cough reflex to remove sputum, reduce pulmonary infection, enhance swallowing function, and raise the success rate of extubation in stroke patients, which is better than scalp acupuncture.


Abundant empty class II MHC molecules on the surface of immature dendritic cells.
A monoclonal antibody specific for the empty conformation of class II MHC molecules revealed the presence of abundant empty molecules on the surface of spleen- and bone marrow-derived dendritic cells (DC) among various types of antigen-presenting cells. The empty class II MHC molecules are developmentally regulated and expressed predominantly on immature DC. They can capture peptide antigens directly from the extracellular medium and present bound peptides to antigen-specific T lymphocytes. The ability of the empty cell-surface class II MHC proteins to bind peptides and present them to T cells without intracellular processing can serve to extend the spectrum of antigens able to be presented by DC, consistent with their role as sentinels in the immune system.


Neural changes following remediation in adult developmental dyslexia.
Brain imaging studies have explored the neural mechanisms of recovery in adults following acquired disorders and, more recently, childhood developmental disorders. However, the neural systems underlying adult rehabilitation of neurobiologically based learning disabilities remain unexplored, despite their high incidence. Here we characterize the differences in brain activity during a phonological manipulation task before and after a behavioral intervention in adults with developmental dyslexia. Phonologically targeted training resulted in performance improvements in tutored compared to nontutored dyslexics, and these gains were associated with signal increases in bilateral parietal and right perisylvian cortices. Our findings demonstrate that behavioral changes in tutored dyslexic adults are associated with (1) increased activity in those left-hemisphere regions engaged by normal readers and (2) compensatory activity in the right perisylvian cortex. Hence, behavioral plasticity in adult developmental dyslexia involves two distinct neural mechanisms, each of which has previously been observed either for remediation of developmental or acquired reading disorders.


Obesity and Pancreatic Cancer: A Matched-Pair Survival Analysis.
Morbid obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC). However, the impact of obesity on postoperative outcomes and overall survival in patients with PDAC remains a controversial topic. Patients who underwent pancreatic surgery for PDAC between 1997 and 2018 were included in this study. Matched pairs (1:1) were generated according to age, gender and American Society of Anesthesiologists status. Obesity was defined according to the WHO definition as BMI ≥ 30 kg/m2. The primary endpoint was the difference in overall survival between patients with and without obesity. Out of 553 patients, a total of 76 fully matched pairs were generated. Obese patients had a mean BMI-level of 33 compared to 25 kg/m2 in patients without obesity (p = 0.001). The frequency of arterial hypertension (p = 0.002), intraoperative blood loss (p = 0.039), and perineural invasion (p = 0.033) were also higher in obese patients. Clinically relevant postoperative complications (p = 0.163) and overall survival rates (p = 0.885) were comparable in both study groups. Grade II and III obesity resulted in an impaired overall survival, although this was not statistically significant. Subgroup survival analyses revealed no significant differences for completion of adjuvant chemotherapy and curative-intent surgery. Obesity did not affect overall survival and postoperative complications in these patients with PDAC. Therefore, pancreatic surgery should not be withheld from obese patients.


The validity of self-reported SARS-CoV-2 results among postpartum respondents.
Rapid and reliable health data on SARS-CoV-2 infection among pregnant individuals are needed to understand the influence of the virus on maternal health and child development, yet the validity of self-reported COVID-19 testing and diagnosis remains unknown. We assessed the validity of self-reported COVID-19 polymerase chain reaction (PCR) testing and diagnosis during delivery among postpartum respondents as well as how diagnostic accuracy varied by respondent characteristics. We validated receipt of a COVID-19 PCR test and test results by comparing self-reported results obtained through an electronic survey to electronic medical record data (gold standard) among a cross-sectional sample of postpartum respondents who delivered at four New York City hospitals between March 2020 and January 2021. To assess validity, we calculated each indicator's sensitivity, specificity and the area under the receiver-operating curve (AUC). We examined respondent characteristics (age, race/ethnicity, education level, health insurance, nativity, pre-pregnancy obesity and birth characteristics) as predictors of reporting accuracy using modified Poisson regression. A total of 276 respondents had matched electronic record and survey data. The majority, 83.7% of respondents received a SARS-CoV-2 PCR test during their delivery stay. Of these, 12.1% had detected SARS-CoV-2. Among those tested, sensitivity (90.5%) and specificity (96.5%) were high for SARS-CoV-2 detection. The adjusted risk ratio (aRR) of accurate result reporting was somewhat lower among Hispanic women relative to white non-Hispanic women (aRR 0.90, 95% CI 0.90, 1.00) and among those who had public or no insurance vs. private (aRR 0.91, 95% CI 0.82, 1.01), controlling for recall time. High recall accuracy result reporting for COVID-19 PCR tests administered during labour and delivery suggest the potential for population-based surveys as a rapid mechanism to obtain accurate data on COVID-19 diagnostic history. Additional psychometric research is warranted to ensure accurate recall across respondent subgroups.


High hepatitis C virus cure rates with approved interferon-free direct-acting antivirals among diverse mainland Chinese patients including genotypes 3a and 3b.
Globally, China has the highest chronic hepatitis C (CHC) burden, but its real-world direct-acting antiviral (DAA) data are limited. Our aim is to investigate the real-world outcome of China Food and Drug Administration-approved DAA therapies across mainland China including those with genotype (GT) 3. The REAL-C is a multinational real-world interferon-free DAA-treated CHC registry of several mainland China and other Asian centers. We evaluated the sustained virological response rate 12 weeks after end of treatment (SVR12), adverse events, and treatment effect on liver function and fibrosis (fibrosis-4 index). We analyzed 859 DAA-treated CHC patients (6/1/2017-5/30/2019) from 12 mainland China centers (three municipalities and nine provinces): median age 52, 49.9% male, 33.1% cirrhosis, 95% treatment naïve, and 2.5% HBsAg+ . The most common GT was GT1b (523, 62.2%), followed by GT2a (156, 18.5%), GT3b (74, 8.8%), GT3a (41, 4.9%), and GT6 (37, 4.4%). SVR12 rates were 98.0% overall (95% confidence interval 96.9-98.8%), 98.1% for GT1b, 96.8% GT2a, 100% GT3a, 97.3% GT3b, and 100% GT6. Baseline cirrhosis and male sex but not prior treatment history, renal dysfunction, age, and GTs were associated with SVR12. For both cirrhotic and non-cirrhotic patients, there were significant improvement in liver function tests, alpha fetoprotein, and fibrosis-4 index with SVR12. Serious adverse events were rare (1.1%) with only nine patients discontinuing therapy prematurely and anemia being the most common adverse event (13.1%, mostly with ribavirin). In real-world Chinese patients with diverse GTs, Chinese Food and Drug Administration-approved interferon-free DAAs were well tolerated, provided high cure rates (98.0% overall) including GT3a/3b, and led to improvement of liver function.


[An information support system for managing the environmental status in the Republic of Bashkortostan].
The main function of informational system supporting environmental control in Bashkortostan Republic is to prevent and liquidate accidents, to provide operative and complete information on current and future state of environment. Functioning of the system is supported by geological informational structure, ecologic databases, space information processor, broad system of mathematic models incorporated into local computer network.


Overexpression of the Key Enzymes in the Methylerythritol 4-phosphate Pathway in Corynebacterium glutamicum for Improving Farnesyl Diphosphate-Derived Terpene Production.
A systematic and combinatorial optimization has been employed to metabolically engineer microbes for identifying key gene targets for overexpression to increase the intermediate pools for terpenoid production. Herein, the methylerythritol 4-phosphate (MEP) pathway in Corynebacterium glutamicum, an industrial host, was investigated to identify the key genes whose overexpression would improve the production of farnesyl diphosphate (FPP)-derived terpenoids (squalene and α-farnesene). Using a combinatorial approach with the single, double, and triple expression of genes in the MEP pathway in a high-throughput fermentation, overexpression of the ispDF genes, along with the known dxs and idi genes, was most effective at increasing the squalene contents, i.e., by 14-fold. The dxr gene was identified as the key target enzyme for α-farnesene production. This result could provide fundamental information for improving the metabolic engineering of C. glutamicum for terpene production via an optimized MEP pathway.


The Fish Pathogen Vibrio vulnificus Biotype 2: Epidemiology, Phylogeny, and Virulence Factors Involved in Warm-Water Vibriosis.
Vibrio vulnificus biotype 2 is the etiological agent of warm-water vibriosis, a disease that affects eels and other teleosts, especially in fish farms. Biotype 2 is polyphyletic and probably emerged from aquatic bacteria by acquisition of a transferable virulence plasmid that encodes resistance to innate immunity of eels and other teleosts. Interestingly, biotype 2 comprises a zoonotic clonal complex designated as serovar E that has extended worldwide. One of the most interesting virulence factors produced by serovar E is RtxA13, a multifunctional protein that acts as a lethal factor for fish, an invasion factor for mice, and a survival factor outside the host. Two practically identical copies of rtxA13 are present in all biotype 2 strains regardless of the serovar, one in the virulence plasmid and the other in chromosome II. The plasmid also contains other genes involved in survival and growth in eel blood: vep07, a gene for an outer membrane (OM) lipoprotein involved in resistance to eel serum and vep20, a gene for an OM receptor specific for eel-transferrin and, probably, other related fish transferrins. All the three genes are highly conserved within biotype 2, which suggests that they are under a strong selective pressure. Interestingly, the three genes are related with transferable plasmids, which emphasizes the role of horizontal gene transfer in the evolution of V. vulnificus in nutrient-enriched aquatic environments, such as fish farms.


Hydrogen peroxide and extracellular signal-related kinase 1/2 pathway regulate ferritin levels in retinal pigmented and lens epithelial cells.
Iron plays a central role in the oxidative stress caused by hydrogen peroxide. The ubiquitous iron storage protein, ferritin, safely sequesters iron, reducing its ability to cause oxidative damage. Oxidative stress can activate mitogen-activated protein (MAP) kinase pathways with many downstream effects. The purpose of this study was to determine the effects of hydrogen peroxide on MAP kinase pathways (extracellular signal-related kinase [ERK]1/2, c-Jun N-terminal kinase [JNK], and p38) and ferritin levels in canine lens and retinal epithelial cells (lens epithelial cells [LECs] and retinal pigmented epithelial [RPE] cells). Primary cultures of canine LECs and RPE cells were used in these studies. Hydrogen peroxide was delivered either by a single 250 μM bolus or 0.25 mU/ml glucose oxidase (GO). Immunoblotting was used to determine the activation of the MAP kinase pathways. Ferritin was detected with enzyme immunosorbent assay. Baseline activation of ERK1/2 in the untreated RPE cells and LECs was decreased by treatment with U-0126. Bolus hydrogen peroxide greatly increased ERK1/2 activation that had been blocked by U-0126, whereas GO had no significant effect on ERK1/2 phosphorylation. Hydrogen peroxide, either bolus or constant low levels, increased ferritin levels in the LECs and RPE cells. Surprisingly, U-0126 not only did not inhibit the effect of hydrogen peroxide on the ferritin levels but also increased the ferritin levels in both cell types. Neither bolus nor chronic hydrogen peroxide exposure activated the JNK or p38 pathway. Additionally, neither JNK nor p38 inhibitors had any effect on the ferritin concentrations in the LECs or RPE cells. Although U-0126 inhibited the hydrogen peroxide-induced increase in ERK1/2 phosphorylation, U-0126's lack of inhibition of the peroxide-induced increase in intracellular ferritin levels indicates that this pathway is not involved in ferritin induction by hydrogen peroxide. This is the first study to demonstrate that hydrogen peroxide and an inhibitor of ERK1/2 activation can increase the levels of the iron storage protein, ferritin. Since ferritin can shield cells from iron-catalyzed damage, this downstream effect likely plays a protective role, which, in the case of the ERK1/2 inhibitor, U-0126, demonstrates a potential therapeutic target.


M.D. mobility express: are you ready to facilitate total physician mobility?
With new technologies erupting across the IT landscape, physician mobility is expected to leap forward in the coming years. But healthcare IT leaders and industry experts say thoughtful strategies and clear vision will be needed to make the mobile future a successful one for all those involved.


CK2 interacting proteins: emerging paradigms for CK2 regulation?
Protein kinase CK2 represents a small family of highly conserved protein kinases involved in a complex series of cellular events. Furthermore, CK2 has been localised to many discrete cellular sites and has an extensive and diverse array of substrates and interaction partners in cells. Despite considerable investigation, the precise mechanism(s) of regulation of CK2 in cells remains poorly understood. In consideration of the prospect that cells contain many distinct sub-populations of CK2 that are distinguished on the basis of localisation and/or interactions with other cellular components, one possibility is that there may be differential regulation of specific sub-populations of CK2. With this in mind, some of the individual sub-populations of CK2 may be regulated through particular protein-protein interactions that may play a role in recruiting CK2 into the vicinity of its substrates and/or modulating its ability to phosphorylate specific cellular targets. In this respect, here we examine two CK2-interacting proteins, namely Pin1 and CKIP-1 that have been shown to participate in the modulation of CK2 specificity or the subcellular localisation of CK2, respectively. One aspect of this work has been focused on the prospect that Pin1 interacts with CK2 in response to UV stimulation in a manner analogous to the phosphorylation-dependent interactions of CK2 that occur following the mitotic phosphorylation of CK2. A second aspect of this work involves an examination of the structural basis for interactions between CK2 and CKIP-1 with emphasis on a putative HIKE domain in CK2.


Involvement of intracellular Ca2+ dynamics in cytoprotective action by amino acids and cytotoxicity by sodium laurate, an absorption enhancer.
In our previous studies, taurine (Tau) and L-glutamine protected intestinal epithelial cells from local toxicity caused by sodium laurate (C12), an absorption enhancer, while maintaining sufficient absorption-enhancing effect of C12, and it was suggested that one of the mechanisms behind cytoprotection by amino acids was to prevent intracellular Ca2+ concentration ([Ca2+]i) from increasing. In the present study, we focused on the elucidation of mechanisms by which C12 increases [Ca2+]i and by which amino acids suppress [Ca2+]i by utilizing Caco-2 cells. Removal of extracellular Ca2+ remarkably suppressed the increase of [Ca2+]i by C12. Compound 48/80, an inhibitor of phospholipase C, and verapamil, a Ca2+ channel inhibitor, also significantly prevented [Ca2+]i elevation. These results indicate that C12 augmented [Ca2+]i due to (a) influx of extracellular Ca2+ through Ca2+ channel, (b) release of Ca2+ from the endoplasmic reticulum. Cytoprotective action by amino acids was significantly attenuated by orthovanadate, an inhibitor of plasma membrane Ca2+-ATPase (PMCA), suggesting that amino acids activate PMCA to enhance the efflux of intracellular Ca2+. Furthermore, Tau enhanced the mitochondrial uptake of Ca2+, which could contribute to the decrease in [Ca2+]i. These results clearly show that amino acids protect intestinal epithelial cells from being damaged by modulating intracellular Ca2+ dynamics.


Fundamental properties of digital images.
The quality of a digital image is affected by matrix size, unsharpness in the underlying image, bit depth, and noise in the underlying image. The array of all of the pixels into which an image is divided is the image matrix. If the image matrix is small (ie, composed of a few large pixels), the resolution of the digital image is low. Image blur dominates when the pixel size is much smaller than the unsharpness of the underlying image. The density in a pixel is represented by a binary number with a variable number of bits (bit depth). The more noise present in the initial image, the fewer the bits that are needed to convey its representation. Insufficient numbers of bits in the digital representation of an image, whether from too few pixels or too small a bit depth in each pixel, result in inadequate image quality. Use of too many bits, relative to the quality of the underlying image, places an increasingly unwarranted demand on digital image handling and processing.


Acute kidney injury in moderate and severe COVID-19 patients: Report of two university hospitals.
Acute kidney injury (AKI) is one of the most severe complications of SARS-CoV-2 infection. In a retrospective study, we aimed to describe the influence of COVID-19-related factors on the severity, outcome and timing of AKI in 268 patients admitted in two large COVID-19-designated university hospitals over a period of 6 months. In the univariate analysis, there was a significant relationship between KDIGO stage and the extension of COVID-19 pneumonia on computed tomography (CT), need for oxygen supplementation, serum levels of ferritin, interleukin-6, and procalcitonin, but none of these variables had a value for predicting KDIGO stage in multinomial regression. The odds of recovery of renal function were significantly diminished by d-dimer values. Lack of immunomodulatory treatment was found to be correlated with increased need for renal replacement therapy (RRT). Compared with AKI at admission, hospital-acquired AKI was predicted by the severity of lung damage on CT, evolved more frequently with incomplete recovery of renal function, and was significantly associated with antiviral therapy.


The changing suicide pattern in Canadian adolescents and youth, compared to their American counterparts.
Canada has a high rate of suicide among adolescents and youth--higher than the rate in the United States. The study of variation in societal suicide rates is still guided primarily by Durkheim's (1897) theory which proposed a primarily social integration/regulation theory of suicide. There is evidence that social and economic predictors of suicide vary depending upon the particular subgroup--women or men, and young or old. Rates of birth, divorce, marriage, and unemployment were analyzed and compared to rates of suicide from 1965-1985 in Canada and the United States for particular subgroups. In Canada, measures of domestic integration (divorce and birth rates) and the economy (unemployment rate) predicted youth suicide rates more successfully than they did adult suicide rates. In the United States for the same period, there was less variation in the predictors of suicide by age. Further research as well as caution about overgeneralizing the results are warranted.


Habitat selection by marine larvae in changing chemical environments.
The replenishment and persistence of marine species is contingent on dispersing larvae locating suitable habitat and surviving to a reproductive stage. Pelagic larvae rely on environmental cues to make behavioural decisions with chemical information being important for habitat selection at settlement. We explored the sensory world of crustaceans and fishes focusing on the impact anthropogenic alterations (ocean acidification, red soil, pesticide) have on conspecific chemical signals used by larvae for habitat selection. Crustacean (Stenopus hispidus) and fish (Chromis viridis) larvae recognized their conspecifics via chemical signals under control conditions. In the presence of acidified water, red soil or pesticide, the ability of larvae to chemically recognize conspecific cues was altered. Our study highlights that recruitment potential on coral reefs may decrease due to anthropogenic stressors. If so, populations of fishes and crustaceans will continue their rapid decline; larval recruitment will not replace and sustain the adult populations on degraded reefs.


International indoor and outdoor evaluation of Bacillus sphaericus products: complexity of standardizing outdoor protocols.
Only one Bacillus sphaericus strain, strain 2362, is currently used commercially to control Culex larval populations. A reliable methodology, easily used, was developed to identify new strains for field application. Larvicidal activities of 3 highly mosquitocidal strains, strains C3-41, Mal, and LB24, previously selected in the laboratory, were compared with that of strain 2362 in tropical and European countries. The following steps were performed: production and titration of acetonic powders from these 4 strains on local Culex species, survey of initial and residual activity under standardized indoor and outdoor conditions, and evaluation of the efficacy of liquid formulations of the 4 strains in natural breeding sites of Culex. In indoor conditions, strain C3-41 showed the highest activity on both Culex pipiens and Culex quinquefasciatus; strain Mal was the least active. The residual activity causing 80% mortality differed from 20 to 90 days according to the strains and the country. Outdoor experiments with powders (0.02-1.6 mg/liter) were performed and the initial toxicities were similar in all cases. Residual activities were very different, from 6 to 95 days posttreatment. Liquid formulations were applied to larval habitats (from 0.1 to 10 g/m2). In tropical countries, larval recolonization in cesspits or ponds occurred after 10-35 days. In Europe, higher doses were needed in polluted water than in clear water (from 3 to 10 liter/ha) for the same control, and the time before 80% residual activity was reached was less than 9-12 days. However, in cesspits, residual activity could be observed for 12 days to 5 mo. A strain 3-5 times more active than the others in bioassays is not significantly detectable from those strains in field trials.


Defective Circulating Regulatory B Cells in Patients with Dilated Cardiomyopathy.
Newly identified IL-10-producing regulatory B cells (Bregs) have been shown to play an important role in the suppression of immune responses. Chronic immune activation participates in the pathogenesis of dilated cardiomyopathy (DCM) but whether Bregs are involved in its development remains unclear. We aimed to investigate the circulating frequency and function of Bregs in DCM. In total, 35 DCM patients (20 men and 15 women) and 44 healthy controls (23 men and 21 women) were included in the experiment, and the frequency of Bregs was detected using flow cytometry. According to our results, the frequency of circulating IL-10-producing Bregs was significantly lower in DCM patients compared with healthy controls. Furthermore, the CD24hiCD27+ B cell subset in which IL-10-producing Bregs were mainly enriched from DCM patients showed impaired IL-10 expression and a decreased ability to suppress the TNF-α production of CD4+CD25- Tconv cells and to maintain Tregs differentiation. Correlation analysis showed that the frequency of IL-10-producing Bregs and the suppressive function of CD24hiCD27+ B cells were positively correlated with left ventricular ejection fraction and negatively correlated with NT-proBNP in DCM patients. In conclusion, the reduced frequency and impaired functions suggest a potential role of Bregs in the development of DCM.


Osteopontin expression and its possible functions in the aortic disorders and coronary artery disease.
Osteopontin (OPN) has been verified to be closely associated with oncogenesis and remodeling processes. But this cytokine was rarely assessed in the presence of aortopathies, especially acute aortic dissection. The aim of the present study was to evaluate the expressions of OPN by way of molecular biological approaches so as to offer a better understanding of the possible mechanisms of the aortopathies. Consecutive patients with type A acute aortic dissection (20 patients), aortic aneurysm (nine patients) or coronary artery disease (21 patients) referred to this hospital for surgical operations were enrolled into this study. Blood samples of the surgical patients after systematic heparinization, and control fast morning blood samples drawn from 21 young healthy volunteers who had no evidence of any healthy problems were investigated for enzyme linked immunosorbent assay (ELISA). The surgical specimens of the aortic tissues collected from the surgical patients during the operations were obtained for quantitative realtime reverse transcription polymerase chain reaction (RT-PCR) for OPN mRNA, western blot assay for OPN protein, and for immunohistochemical staining of OPN. Ascending aortic tissues from the autopsies of the healthy individuals dying of accident were obtained as controls of immunohistochemistry. By quantitative RT-PCR, the expressions of OPN mRNA were all upregulated in all three surgical groups. The quantitative results did not reveal any intergroup differences. Western blot assay revealed that OPN was positive with similar intensities of expressions in all three surgical groups. Quantitative western blot analyses of OPN expressions did not show any significance between groups. The OPN expressions by ELISA in the aortic tissue were 3.09311 ± 1.65737, 3.40414 ± 1.15095, and 1.68243 ± 0.31119 pg/mg protein in the aortic dissection, aortic aneurysm, and coronary artery disease groups, respectively. The OPN level of the patients with coronary artery disease was much lower than those with aortic dissection (P = 0.033) or with aortic aneurysm (P = 0.019). By unparametric tests, there were significant differences in the aortic OPN contents among aortic dissection, aortic aneurysm and coronary artery disease groups (P < 0.01). A significant direct correlation was present between plasma OPN concentration and the time interval from the onset to surgery of aortic dissection (Y = 0.1420X + 2.4838, r² = 0.5623, r = 0.750, P = 0.032). By immunohistochemistry, OPN was expressed in the aortic cells: in the intima, it was weaker in all three surgical groups in comparison with the healthy control; in the media, it was weak in the aortic dissection, intense positive in aortic aneurysm, focal positive in the coronary artery disease, but evenly positive in the healthy control groups; and in the adventitia, it was positive in the aortic dissection, coronary artery disease and healthy control groups, but weak positive in the aortic aneurysm group. These data may provide evidences that OPN may play a role in the pathogenesis of aortopathies including aortic dissection, aortic aneurysm, and coronary artery disease. OPN might be of potential perspective as a clinically diagnostic tool in the evaluations of the complex remodeling process incorporating vascular injury and repair.


[Etiological analysis of influenza surveillance data in Xuzhou from 2005 to 2011].
To investigate the prevalence and subtypes of influenza viruses in Xuzhou city from 2005 to 2011 and to provide the scientific supports for influenza prevention and control in this religion. The throat swab samples were collected from the influenza-like cases from national influenza like illness sentinel hospital in Xuzhou. The samples were used for influenza virus isolation and identification, sent on the national flu center to confirm according to the "national influenza surveillance program" and "influenza virus and experimental technology". From Oct. 2005 to Dec. 2011, a total of 9561 swab specimens were collected in which 1152 strains were identified for influenza viruses with total isolated rate of 12.0%. Among these strains, 708 strains were A1 (H1N1) subtype (14.2%), 466 strains were A3 (H3N2) subtype (40.5%), 78 strains were new H1N1 subtype (6.8%), 362 strains were BV (Victoia) subtype (31.4%) and 82 strains were BY (Yamagate) subtype (7.1%). The top detection rate (25.9%) arose in 2007, secondary detection rate (17.4%) occurred at 2009 and the lowest one (2.3%) appeared in 2011. From the winter of 2005 to the spring of 2006 A1 (H1N1) subtype had appeared as predominant strains but in the winter of 2006 the predominant strains were BV subtype. It changed to A3 subtype in 2007 to 2009 and the other three dominant strains were A1, BV and BY in 2008. In the winter of 2009, both A3 (H3N2) and new H1N1 subtype were predominant strains. BV subtype was predominant strains in 2010 to 2011. The prevalence of A3 subtype appeared in all the year while prevalence of BV only arose in the spring and winter. So the detection rate was high in January (34.4%) but low in August (2.2%). The influenza population is correlated with age, the highest detection rate arose in 5-age group and the lowest detection rate appeared in 25-age group. Influenza subtype A1, A3, New H1N1 are all appeared as predominant strains in Xuzhou city from 2005 to 2010. Besides, the prevalence of BV subtype is stronger in recently.


Initial clinical outcomes and prognostic variables in the implementation of a Code Sepsis in a high complexity University Hospital.
To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient´s epidemiological and clinical characteristics and prognostic factors. A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p <0.05), lactic acid (6.10 vs 2.62 mmol/L, p <0.05) and procalcitonin (23.27 vs 12.73 mg/dL, p<0.05). A statistically significant linear trend was found between SOFA scale rating and mortality (p<0.05). In the multivariate analysis additional independent risk factors associated with death were identified: age > 65 years (OR 5.33, p <0.05), lactic acid > 3 mmol/L (OR 5,85, p <0,05), creatinine > 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programs.


The prevalence of parasites in commonly used leafy vegetables in South Western, Saudi Arabia.
To determine the degree of contamination caused by parasites in commonly used leafy vegetables in Abha, Kingdom of Saudi Arabia (KSA). We carried out the study in the Department of Clinical Microbiology and Parasitology, King Khalid University, Abha, KSA, during the period September 2004 to May 2005. Five commonly used leafy vegetables, namely, green onion, radish, watercress, lettuce and leek, were washed each in water and Tris-buffer-saline (TBS). The washing solution was then centrifuged and the sediments were examined for parasites. The use of TBS for the extraction, significantly increased the isolation rate (27.2%) of the parasites compared with the use of tap water (7.8%) (z=4.72 p<0.001). The prevalence of the parasites was 28% in green onion, 25% in radish, 17% in watercress, 17% in lettuce, and 13% in leek. The parasites were more common in the months of September to December. Ankylostoma duodenale, Entameba coli, Ascaris lumbricoides and Blastocystis hominis were the most common isolated parasites. We encountered 12 genera of parasites during the study and the least common was iodamoeba butschlii. The study shows that parasites are common in leafy vegetables and the use of tap water does little to remove them. The public health implications of our findings will be communicated to the Aseer regional health authorities for appropriate community health education and other necessary actions.


Paediatric analgesia. Which drug? Which dose?
The pharmacological management of paediatric pain is an area which is undergoing considerable development. Improvements in pain management are coming from appreciation of the special problems of children, increased knowledge of drug pharmacology and the development of better methods of drug delivery. Traditional methods of postoperative analgesia such as intramuscular injections are disliked by children and are being replaced by intravenous infusions, patient-controlled analgesia (PCA) and epidural opioids. Local anaesthetic blocks offer the benefit of fewer side effects and for certain procedures can provide complete pain relief in the immediate postoperative period. Inhaled analgesics such as nitrous oxide can be adapted for use in children and provide excellent analgesia for short painful procedures. The pain from needles is reduced considerably by the use of local anaesthetic creams. There has been greater appreciation of the benefits of drug combination, particularly with cancer pain management, and the importance of providing long term analgesia for these patients and patients with burns. Considerable scope exists for future developments such as transmucosal and transdermal drug delivery systems and other methods of drug delivery which are suited to the special needs of children.


Iodine-mediated regioselective C2-amination of indoles and a concise total synthesis of (±)-folicanthine.
Highly substituted 2-aminated indoles can be prepared in moderate to excellent yields by regioselective C2-amination of indoles promoted by iodine. As a key step in a concise synthesis of (±)-folicanthine, its core structure was easily obtained by one step cyclization-dimerization of substituted tryptophan in high yield on a gram scale.


Personal Health Budget as a new rehabilitation model for severe mental illness within a caring community: An Italian evaluation study of beneficial effects.
Personal Health Budget has been provided to consumers with severe mental illness within a policy shift toward a person-tailored mental healthcare treatment based on individual unmet needs. Evidence of beneficial effects of Personal Health Budget is still scarce. The aim of this study was to provide preliminary data on clinical and social benefits of adding Personal Health Budget to a standard pharmacotherapy in patients with severe mental illness across a 24-month follow-up period. Participants (n = 137) were individuals with severe mental illness, aged 18-50 years, recruited in one of the adult mental health services of the Parma Department of Mental Health. They completed the Global Assessment of Functioning scale, the Health of the Nation Outcome Scale and the Brief Psychiatric Rating Scale. This age range was chosen to limit Personal Health Budget interventions to adults with a non-prolonged illness duration. Friedman's test for repeated measure was used to assess the longitudinal stability of functioning and clinical parameters. A linear regression analysis was also performed. A significant decrease in all Global Assessment of Functioning scale, Health of the Nation Outcome Scale and Brief Psychiatric Rating Scale scores along the 24 months of follow-up was observed. Regression analysis results specifically showed a relevant association between a Personal Health Budget multiaxial intervention and the longitudinal reduction in Brief Psychiatric Rating Scale 'Negative Symptoms' and Health of the Nation Outcome Scale 'Social Problems' subscores. Our findings support the useful implementation of a Health of the Nation Outcome Scale approach for severe mental illness patients within the Italian mental health service network.


Multiple arithmetic operations in a single neuron: the recruitment of adaptation processes in the cricket auditory pathway depends on sensory context.
Sensory pathways process behaviorally relevant signals in various contexts and therefore have to adapt to differing background conditions. Depending on changes in signal statistics, this adjustment might be a combination of two fundamental computational operations: subtractive adaptation shifting a neuron's threshold and divisive gain control scaling its sensitivity. The cricket auditory system has to deal with highly stereotyped conspecific songs at low carrier frequencies, and likely much more variable predator signals at high frequencies. We proposed that due to the differences between the two signal classes, the operation that is implemented by adaptation depends on the carrier frequency. We aimed to identify the biophysical basis underlying the basic computational operations of subtraction and division. We performed in vivo intracellular and extracellular recordings in a first-order auditory interneuron (AN2) that is active in both mate recognition and predator avoidance. We demonstrated subtractive shifts at the carrier frequency of conspecific songs and division at the predator-like carrier frequency. Combined application of current injection and acoustic stimuli for each cell allowed us to demonstrate the subtractive effect of cell-intrinsic adaptation currents. Pharmacological manipulation enabled us to demonstrate that presynaptic inhibition is most likely the source of divisive gain control. We showed that adjustment to the sensory context can depend on the class of signals that are relevant to the animal. We further revealed that presynaptic inhibition is a simple mechanism for divisive operations. Unlike other proposed mechanisms, it is widely available in the sensory periphery of both vertebrates and invertebrates.


Endangered Salares: micro-disasters in Northern Chile.
This article emerges from a transdisciplinary collaboration between a micro-biologist and an anthropologist deeply concerned with the protection of endangered salares (saltpans) in northern Chile. Our aim is to establish the concept of "micro-disaster" as a tool for examining how extractivism is disrupting salares and their "deep-time" microbial ecologies. These ecologies are key for understanding early events on Earth, as their evolution enabled the oxygenation of the planet 2.5 billion years ago and caused the biodiversity explosion. By considering how being human involves being microorganismal - and how human time is entangled with microorganismic time -, this article connects neoliberal extractivist history with geo-biological evolutionary history. "Micro-disasters" therefore affect us deeply as complex humans, and oblige us to develop further a planet-centered mode of collaborating, thinking, feeling, and acting. In the context of this special issue on extinction, we insist that concerns over extinction must be considered in continuity with deep-time ecologies. We propose to rethink humans as an "environmentally complex we" simultaneously entangled with historical experiential time and microbial "deep-time."


Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer.
Women with breast cancer are more frequently being treated with preoperative neoadjuvant chemotherapy. The reliability of sentinel lymph node biopsy (SLNB) following chemotherapy has not been determined. This was a meta-analysis of studies that examined the results of SLNB after preoperative chemotherapy. Included articles had to meet two criteria. First, patients had to have had operable breast cancer and to have undergone SLNB after preoperative chemotherapy and, second, patients had to have undergone subsequent axillary lymph node dissection. Meta-analyses were performed in which Bayesian hierarchical models were created to estimate the identification rate (IR) and sensitivity of SLNB in this setting. Twenty-one studies were identified that included a total of 1273 patients. The IRs reported ranged from 72 to 100 per cent, with a pooled estimate of 90 per cent. The sensitivity of SLNB ranged from 67 to 100 per cent, with a pooled estimate of 88 (95 per cent confidence interval 85 to 90) per cent. Meta-analyses performed using Bayesian modelling resulted in (posterior) estimates for IR and sensitivity of 91 (95 per cent credible interval 88 to 94) and 88 (95 per cent credible interval 84 to 91) per cent respectively. SLNB is a reliable tool for planning treatment after preoperative chemotherapy.


Hepatitis C treatment in an HIV-HCV-coinfected patient with drug addiction and psychiatric illness: a case report.
Few data are available about the treatment of chronic infection with hepatitis C virus (HCV) in HIV-infected persons with active drug or alcohol addiction and psychiatric disorders. We report the case of a 42-year-old man who entered care with a CD4+ cell count of 78/microL but was reluctant to take many of the available antiretroviral agents. For many years, periods of sobriety and good adherence to antiretroviral medications were interspersed with relapses to heroin, cocaine, and alcohol use as well as episodes of overdose, major depression with psychiatric hospitalization, incarceration, and discontinuation of antiretroviral medications. After 4 years of HIV primary care, the patient was stabilized to begin therapy for hepatitis C with pegylated interferon and ribavirin with the support of a multidisciplinary team. After starting treatment for hepatitis C, the patient achieved an early virologic response and continues to have an undetectable HCV RNA level by polymerase chain reaction testing and 100% adherence to on-site pegylated interferon injections, without adverse events related to his addiction or psychiatric symptoms. This case suggests that HIV-HCV-coinfected persons with the common comorbidities of polysubstance dependence and psychiatric illness may effectively and safely undergo pharmacotherapy for hepatitis C with appropriate support.


Sphingosine regulates the transcription of CYP17 by binding to steroidogenic factor-1.
Steroidogenic factor (SF1, Ad4BP, NR5A1) is a nuclear receptor that is essential for steroid hormone biosynthesis and endocrine development. Recent crystallographic studies have found that phospholipids are ligands for SF1. In the present study, our aim was to identify endogenous ligands for SF1 and characterize their functional significance in mediating cAMP-dependent transcription of human CYP17. Using tandem mass spectrometry, we show that in H295R adrenocortical cells, SF1 is bound to sphingosine (SPH) and lyso-sphingomyelin (lysoSM) under basal conditions and that cAMP stimulation decreases the amount of SPH and lysoSM bound to the receptor. Silencing both acid and neutral ceramidases using small interfering RNA induces CYP17 mRNA expression, suggesting that SPH acts as an inhibitory ligand. SPH antagonized the ability of cAMP and the coactivator steroid receptor coactivator-1 to increase CYP17 reporter gene activity. These studies demonstrate that SPH is a bonafide endogenous ligand for SF1 and a negative regulator of CYP17 gene expression.


Morbidity and medical care utilization of old and very old persons.
This report compares the morbidity, health care and drug utilization, and health status of random samples of HMO-enrolled Medicare beneficiaries ages 65-79, and 80 and over. The population represented 3,683 person-years of Kaiser Permanente eligibility (59.2 percent female). Those 80 and over were 20 percent of the person-years (64.1 percent female). The effects of age and sex on morbidity and utilization were analyzed using log linear models that controlled for eligibility, and using two-way analyses of variance of rates. Few differences were found in the morbidity experiences and utilization rates of the two age groups. Indicators of self-reported health status did differ. The findings support the idea that noninstitutionalized very old persons are the healthy survivors of their cohort. Their health care needs may not be much different than younger old persons in terms of the types and amounts of health care services needed.


Effects of ultraviolet radiation on the transmission process of an intertidal trematode parasite.
The transmission of parasites takes place under exposure to a range of fluctuating environmental factors, one being the changing levels of solar ultraviolet radiation (UVR). Here, we investigated the effects of ecologically relevant levels of UVR on the transmission of the intertidal trematode Maritrema novaezealandensis from its first intermediate snail host (Zeacumantus subcarinatus) to its second intermediate amphipod host (Paracalliope novizealandiae). We assessed the output of parasite transmission stages (cercariae) from infected snail hosts, the survival and infectivity of cercariae, the susceptibility of amphipod hosts to infection (laboratory experiments) and the survival of infected and uninfected amphipod hosts (outdoor experiment) when exposed to photo-synthetically active radiation only (PAR, 400-700 nm; no UV), PAR+UVA (320-700 nm) or PAR+UVA+UVB (280-700 nm). Survival of cercariae and susceptibility of amphipods to infection were the only two steps significantly affected by UVR. Survival of cercariae decreased strongly in a dose-dependent manner, while susceptibility of amphipods increased after exposure to UVR for a prolonged period. Exposure to UVR thus negatively affects both the parasite and its amphipod host, and should therefore be considered an influential component in parasite transmission and host-parasite interactions in intertidal ecosystems.


Active Regulation of Supramolecular Chirality through Integration of CdSe/CdS Nanorods for Strong and Tunable Circular Polarized Luminescence.
Building the cooperativity in artificial self-assembling systems will synergistically reshape their properties and expand their application spectrum. Here, we show how the cooperativity between achiral CdSe/CdS nanorods (NRs) and chiral perylene diimide (PDI)-based molecules is built upon their coassembly. We demonstrate that chirality transfer from chiral molecular assemblies to CdSe/CdS NRs is enabled by the encapsulation of NRs into PDI suprascrolls through chain-chain van der Waals interactions, which in turn gives rise to markedly enhanced circularly polarized luminescence of the nanocomposites. Additionally, the circularly polarized emissive bands of the nanocomposites could be finely tuned by engineering the emissive bands of NRs. More importantly, these nanocomposites are able to invert their chirality when NRs are self-assembled into chiral superlattices under a larger amount of NRs. Detailed mechanistic studies unveil that these jammed NRs assemblies hamper the folding of two-dimensional (2D) chiral nanosheets, which consequently suppress the interlayer excitonic coupling and implement the nanocomposites with inverted chirality. Our finding exemplifies a way to invert the chirality switching from folding to unfolding of 2D supramolecular nanosheets, akin to the chirality inversion in the helix-to-superhelix transition in conventional one-dimensional (1D) supramolecular systems. We also show that the strong van der Waals interactions from aliphatic chains are crucial in achieving such chirality transfer and inversion. Overall, we demonstrate that these achiral CdS/CdSe NRs could serve as artificial molecular chaperones to aid the unfolding of supramolecular nanosheets with controlled chirality.


Genome-Wide Analysis of the Glutathione S-Transferase (GST) Genes and Functional Identification of MdGSTU12 Reveals the Involvement in the Regulation of Anthocyanin Accumulation in Apple.
Anthocyanins have essential biological functions, affecting the development of horticultural production. They are synthesized in the cytoplasm through flavonoid metabolic pathways and finally transported into vacuoles for storage. Plant glutathione S-transferases (GSTs) are multifunctional enzymes involved in anthocyanin transportation. In this study, we identified 38 GSTs from the apple (Malus domestica) genome (HFTH1 Whole Genome v1.0) based on the sequence similarity with the GST family proteins of Arabidopsis. These MdGST genes could be grouped into nine chief subclasses: U, F, L, Z, T, GHR, EF1Bγ, TCHQD, and DHAR. The structures, motifs, three-dimensional models, and chromosomal distribution of MdGST genes were further analyzed. Elements which are responsive for some hormones and stress, and others that involve genes related to flavonoid biosynthesis were forecast in the promoter of MdGST. In addition, we identified 32 orthologous gene pairs between apple and Arabidopsis. These genes indicated that numerous apple and Arabidopsis counterparts appeared to be derived from a common ancestor. Amongst the 38 MdGST genes, MdGSTU12 was considerably correlated with anthocyanin variation in terms of extracting expression profiles from reported. Finally, further functional identification in apple transgenic calli and subcellular localization confirmed that MdGSTU12 was of great significance in anthocyanin accumulation in apple.


Virtual cycling effort is dependent on power update rate.
Cycling ergometer protocols are commonly integrated with a virtual reality environment (VRE), especially because of its static position that also allows multiple exercise experiments. Concerning VRE scenarios, visually delayed situations like the ones produced at excessive low update rates can also affect the sense of presence and physiological responses. However, the main interface between the subject and a cycling VRE is the power applied over the crank, and there are only a few experiments to evaluate the effect of delayed situations on this particular interface. Thus, this work aims to investigate the effects of the power update rate (PUR) over the subject`s performance on an avatar-based simulator during a drafting task. A custom cycling VRE was built, and 21 male recreational cyclists (175.9 ± 7.5 cm; 76.5 ± 13.9 kg) were tested at six different PUR levels from 100 to 3000 ms. As a result, PUR affects performance scores (virtual distance, efficiency, and heart rate, p < 0.01) at the given VRE conditions. The case-by-case analysis of the groups reveals that higher update rates always lead to a statistical equivalent or superior performance. Nevertheless, no parameter shows any group difference between 500 ms and lower PUR. These results suggest that virtual cycling protocols should consider PUR and other delay-related mechanisms as possible intervening factors over physiological responses and performance scores.


Delayed Gastric Emptying Post-Esophagectomy: A Single-Institution Experience.
Delayed gastric emptying (DGE) is a common functional disorder after esophagectomy in patients with esophageal carcinoma. Management of DGE varies widely and it is unclear how comorbidities influence the postoperative course. This study sought to determine factors that influence postoperative DGE. This retrospective study evaluates patients who underwent esophagectomy with gastric pull-up between 2007 and 2019. The cohort was stratified in various ways to determine if postoperative care and outcomes differed, including patient demographics, comorbidities, intraoperative and postoperative procedures. During the study period, 149 patients underwent esophagectomy and 37 had diabetes. Overall incidence of DGE, as defined in this study, was 76.5%. Surgery type was significantly different between DGE and normal emptying cohorts (P = 0.005). Comparing diabetic and nondiabetic patients, there was no significant difference noted in DGE (P = 0.25). Additionally, there was no difference in presence of DGE for patients who underwent any intraoperative pyloric procedure compared to those who did not (P = 0.36). Of significance, all 16 patients with chronic obstructive pulmonary disease had a delay in gastric emptying (P = 0.01). A higher proportion of patients with DGE post-esophagectomy were identified compared to the literature. There is little consensus on a true definition of DGE, but we believe this definition identifies patients suffering in the immediate postoperative period and in follow-up. There is no evidence to support a different postoperative course for patients with diabetes, but the link between chronic obstructive pulmonary disease and DGE warrants further investigation.


Cloning of metK from Actinoplanes teichomyceticus ATCC31121 and effect of its high expression on antibiotic production.
A metK gene encoding S-adenosyl-L-methionine synthetase was cloned from the non-Streptomyces actinomycetes, Actinoplanes teichomyceticus ATCC31121. In order to evaluate the effect of the metK expression on antibiotic production in actinomycetes, an expression vector harboring the metK gene was constructed and introduced into Streptomyces lividans TK24 and A. teichomyceticus, and the antibiotic production of the exconjugants was assessed. As a result, it was determined that the expression of metK induced 17-fold and 2.2-fold increases in actinorhodin production from S. lividans TK24 and teicoplanin production from A. teichomyceticus, respectively, compared with the control strains.


Constant-current supply of 3 ppm stability and resettability; application for a SQUID.
We describe a new design for a constant-current supply which is stable and resettable to 3 ppm over a period of one week, even in the presence of ambient temperature changes of several degrees. These characteristics are achieved by utilizing a digital-to-analog converter for providing a changeable, yet extremely stable, reference voltage. Seven full-scale current ranges are available between 0.1 and 100 mA. It is also shown that this constant-current supply is suitable even for use with a SQUID, meeting all of the exacting requirements for such use.


Bloodstream infections in patients with or without cancer in a large community hospital.
Cancer is associated with an increased risk of acquiring bloodstream infection (BSIs). Most knowledge on pathogens and outcome are derived from specialised cancer centres. We here sought to compare causative micro-organisms in BSIs in patients with or without cancer in a 600-bed teaching community hospital. We analysed all positive blood cultures from adult patients between January 2005 and January 2011. A total of 4,918 episodes of BSI occurred in 2,891 patients, of whom 13.4% had a diagnosis of cancer (85.5% with a solid tumour). In both patient groups, Gram-positive isolates were more prevalent (58.7 and 61.4% in patients with and without cancer, respectively) than Gram-negative isolates (31.8 and 32.3%, respectively). Amongst Gram-positive organisms, coagulase-negative staphylococci, Staphylococcus aureus and enterococci were the most frequently isolated in both patient groups; in cancer patients, twice as many BSIs were caused by Enterococcus faecalis and E. faecium. Amongst Gram-negative organisms, Escherichia coli was the most common isolate; in cancer patients, twice as many BSIs were caused by Pseudomonas aeruginosa and Enterobacter cloacae. Yeasts were grown from 3.0% of blood cultures from cancer patients compared to 1.5% of cultures from non-cancer patients. Cancer patients had a 90-day mortality of 35.8% following BSI compared to 23.5% in patients without cancer. These data demonstrate distinct BSI pathogens and impaired outcomes in patients with cancer in the setting of a large community teaching hospital.


The amiodarone derivative KB130015 activates hERG1 potassium channels via a novel mechanism.
Human ether à go-go related gene (hERG1) potassium channels underlie the repolarizing I(Kr) current in the heart. Since they are targets of various drugs with cardiac side effects we tested whether the amiodarone derivative 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015) blocks hERG1 channels like its parent compound. Using patch-clamp and two-electrode voltage-clamp techniques we found that KB130015 blocks native and recombinant hERG1 channels at high voltages, but it activates them at low voltages. The activating effect has an apparent EC(50) value of 12microM and is brought about by an about 4-fold acceleration of activation kinetics and a shift in voltage-dependent activation by -16mV. Channel activation was not use-dependent and was independent of inactivation gating. KB130015 presumably binds to the hERG1 pore from the cytosolic side and functionally competes with hERG1 block by amiodarone, E4031 (N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4-piperidinyl] carbonyl] phenyl] methanesulfonamide dihydrochloride), and sertindole. Vice versa, amiodarone attenuates hERG1 activation by KB130015. Based on synergic channel activation by mallotoxin and KB130015 we conclude that the hERG1 pore contains at least two sites for activators that are functionally coupled among each other and to the cavity-blocker site. KB130015 and amiodarone may serve as lead structures for the identification of hERG1 pore-interacting drugs favoring channel activation vs. block.


Activation of blood coagulation factor VIIa with cleaved tissue factor extracellular domain and crystallization of the active complex.
Exposure of blood to tissue factor leads to the formation of a high affinity tissue factor/factor VIIa complex which initiates blood coagulation. As a first step toward obtaining structural information of this enzyme system, a complex of active-site inhibited factor VIIa (F.VIIai) and soluble tissue factor (sTF) was prepared for crystallization. Crystals were obtained, but only after long incubation times. Analysis by SDS-PAGE and mass spectrometry indicated the presence of sTF fragments similar to those formed by proteolytic digestion with subtilisin (Konigsberg, W., Nemerson, Y., Fang, C., Lin, T.-C. Thromb. Haemost. 69:1171, 1993). To test the hypothesis that limited proteolysis of sTF facilitated the crystallization of the complex, sTF fragments were generated by subtilisin digestion and purified. Analysis by tandem mass spectrometry showed the presence of nonoverlapping N- and C-terminal sTF fragments encompassing more than 90% of the tissue factor extracellular domain. Enzymatic assays and binding studies demonstrated that an equimolar mixture of N- and C-terminal fragments bound to factor VIIa and fully restored cofactor activity. A complex of F.VIIai and sTF fragments was prepared for crystallization. Crystals were obtained using microseeding techniques. The best crystals had maximum dimensions of 0.12 x 0.12 x 0.6 mm and showed diffraction to a resolution of 3 A.


Reliability of alternative devices for postoperative patient temperature measurement: two prospective, observational studies.
Peri-operative hypothermia is associated with significant morbidity, yet limitations exist regarding non-invasive temperature assessment in the post-anaesthesia care unit (PACU). In this prospective study of 100 patients, we aimed to determine the reliability of two commonly used temperature measurement devices, forehead temporal artery temperature and tympanic measurement, in addition to an indwelling urinary catheter with temperature probe, in comparison with the final nasopharyngeal core temperature at the end of surgery. Agreement of forehead measurement with nasopharyngeal temperature showed a mean bias (±95% limits of agreement) of 0.15 °C (±1.4 °C), with a steep slope of the relationship on the Bland-Altman plot of -0.8, indicating a tendency to normalise patient temperature readings to 36.4 °C. Only 54% of hypothermic cases were correctly detected by the forehead measurement device. Agreement of tympanic measurement with nasopharyngeal core temperature measurement was marginally improved with a mean bias of 0.13 °C (95% limits of agreement ±1.15 °C). In contrast, agreement of bladder temperature with nasopharyngeal temperature showed a mean (SD) bias of 0.19 (0.28) °C (95% limits of agreement ±0.54 °C), with a relatively flat line of best fit. We demonstrated that two commonly used temperature measurement devices, forehead temporal artery temperature and tympanic measurement, compared with nasopharyngeal core temperature, were imprecise and unreliable following major surgery. However, the indwelling catheter with temperature sensor was precise and acceptable for continuous core temperature measurement in the PACU.