Engineered optical properties of silver-aluminum alloy nanoparticles embedded in SiON matrix for maximizing light confinement in plasmonic silicon solar cells.
Self-assembled silver-aluminum (Ag-Al) alloy nanoparticles (NPs) embedded in SiO2, Si3N4, and SiON dielectric thin film matrices explored as a hybrid plasmonic structure for silicon solar cells to maximize light confinement. The Ag2Al NPs prepared by ex-vacuo solid-state dewetting, and alloy formation confirmed by X-ray diffraction and photoelectron spectroscopy analysis. Nanoindentation by atomic force microscopy revealed better surface adhesion of alloy NPs on silicon surface than Ag NPs due to the Al presence. The SiON spacer layer/Ag2Al NPs reduced silicon average reflectance from 22.7% to 9.2% due to surface plasmonic and antireflection effects. The SiON capping layer on NPs reduced silicon reflectance from 9.2% to 3.6% in wavelength region 300-1150 nm with preferential forward light scattering due to uniform Coulombic restoring force on NPs' surface. Minimum reflectance and parasitic absorptance from 35 nm SiON/Ag2Al NPs/25 nm SiON structure reflected in plasmonic cell's photocurrent enhancement from 26.27 mA/cm2 (of bare cell) to 34.61 mA/cm2 due to the better photon management. Quantum efficiency analysis also showed photocurrent enhancement of cell in surface plasmon resonance and off-resonance regions of NPs. We also quantified dielectric thin film antireflection and alloy NPs plasmonic effects separately in cell photocurrent enhancement apart from hybrid plasmonic structure role.


[The results of breast conserving treatment in breast cancer].
The aim of the work was to assess the results of breast conserving treatment (BCT) in early breast cancer in patients treated in Lower Silesian Oncology Centre. Analysis of data from 167 women treated between 1997 and June 2003 with BCT and adjuvant therapy was performed. Only in 14 patients (8.3%) failure of treatment was observed. In 7 cases (4.8%) there was local recurrence, all of them underwent mastectomy m. Patey and they are all alive without disease symptoms. In 6 women (3.6%) dissemination of cancer was observed. Death of 5 patients (3%) between 21 and 68 months from operation took place. In Cox-Mantel test only dependency between N status and dissemination (p < 0.05) was noted. Better results of treatment were connected with estrogen receptor (ER) overexpression. Our results do not differ from data published by leading oncology centers around the world.


Peripheral T-Cell Lymphoma: From Biological Research to New Therapies.
This series of six articles (four reviews and two original articles) is presented by international leaders on peripheral T-cell lymphomas (PTCL) [...].


Restless Legs Syndrome in Children and Adolescents.
Children with psychiatric comorbidities frequently are referred for evaluation of sleep complaints. Common sleep symptoms can include difficulty falling asleep, frequent nocturnal awakening, restless sleep, and symptoms of restless legs syndrome (RLS). The understanding of the sleep condition in relation to the psychiatric comorbidity often is a challenge to the physician and often sleep disorders remain undiagnosed, untreated, or undertreated. Restless legs syndrome has been associated with psychiatric comorbidities and with certain medications, such as antidepressants, antihistamines, and antipsychotics. This article reviews the presentation of RLS and restless sleep, the association with psychiatric comorbidities, and treatment options.


Lithium effects on circadian rhythms in fibroblasts and suprachiasmatic nucleus slices from Cry knockout mice.
Lithium is widely used as a treatment of bipolar disorder, a neuropsychiatric disorder associated with disrupted circadian rhythms. Lithium is known to lengthen period and increase amplitude of circadian rhythms. One possible pathway for these effects involves inhibition of glycogen synthase kinase-3β (GSK-3β), which regulates degradation of CRY2, a canonical clock protein determining circadian period. CRY1 is also known to play important roles in regulating circadian period and phase, although there is no evidence that it is similarly phosphorylated by GSK-3β. In this paper, we tested the hypothesis that lithium affects circadian rhythms through CRYs. We cultured fibroblasts and slices of the suprachiasmatic nucleus (SCN), the master circadian pacemaker of the brain, from Cry1-/-, Cry2-/-, or wild-type (WT) mice bearing the PER2:LUC circadian reporter. Lithium was applied in the culture medium, and circadian rhythms of PER2 expression were measured. In WT and Cry2-/- fibroblasts, 10mM lithium increased PER2 expression and rhythm amplitude but not period, and 1mM lithium did not affect either period or amplitude. In non-rhythmic Cry1-/- fibroblasts, 10mM lithium increased PER2 expression. In SCN slices, 1mM lithium lengthened period ∼1h in all genotypes, but did not affect amplitude except in Cry2-/- SCN. Thus, the amplitude-enhancing effect of lithium in WT fibroblasts was unaffected by Cry2 knockout and occurred in the absence of period-lengthening, whereas the period-lengthening effect of lithium in WT SCN was unaffected by Cry1 or Cry2 knockout and occurred in the absence of rhythm amplification, suggesting that these two effects of lithium on circadian rhythms are independent of CRYs and of each other.


Patient with the mesomelic dysplasia, Nievergelt syndrome, and cerebellovermian agenesis and cataracts.
We describe a 33-day-old boy who had short and thick tibiae, symmetrical oligosyndactyly of the hands, and distinctive face. The patient was considered as a case of Nievergelt syndrome, a rare form of mesomelic dysplasia. Besides the characteristic mesomelic limb anomalies of Nievergelt syndrome, this patient exhibited two additional features: agenesis of the cerebellar vermis and cataracts, both of which have not been previously reported.


Forecasting hydrologic controls on juvenile anadromous fish out-migration with process-based modeling and machine learning.
River herring (Alosa sp.) are ecologically and economically foundational species in freshwater streams, estuaries, and oceanic ecosystems. The migration between fresh and saltwater is a key life stage of river herring, where the timing and magnitude of out-migration by juveniles can be limited when streams dry and hydrologic connectivity is lost. Operational decisions by water managers (e.g., restricting community water use) can impact out-migration success; however, these decisions are largely made without reliable predictions of outmigration potential across the migration season. This research presents a model to generate short-term forecasts of the probability of herring out-migration loss. We monitored streamflow and herring out-migration for 2 years at three critical runs along Long Island Sound (CT, USA) to develop empirical understandings of the hydrologic controls on out-migration. We used calibrated Soil and Water Assessment Tool hydrologic models of each site to generate 10,000 years of daily synthetic meteorological and streamflow records. These synthetic meteorological and streamflow data were used to train random forest models to provide rapid within-season forecasts of out-migration loss from two simple predictors: current spawning reservoir depth and the previous 30-day precipitation total. The resulting models were approximately 60%-80% accurate with a 1.5-month lead time and 70-90% accurate within 2 weeks. We anticipate that this tool will support regional decisions on spawning reservoir operations and community water withdrawals. The architecture of this tool provides a framework to facilitate broader predictions of the ecological consequences of streamflow connectivity loss in human-impacted watersheds.


Relation between average daily metabolic rate and resting metabolic rate of the mongolian gerbil (Meriones unguiculatus).
Some early reports have claimed that the Mongolian gerbil is a diurnal rodent, but we found it to be active both night and day, being more active at night. A circadian rhythm was found both in locomotory activity under laboratory conditions and in average daily metabolic rate (ADMR).The ADMR of the Mongolian gerbil observed at 20° C in our study was 2.921 ml O2/g·h which was near the value expected from Grodzinski's equation (ADMR=19.94 W-0.50).Both ADMR and RMR were found to be negatively correlated with ambient temperature, with the slope of the regression line for ADMR being less than that for RMR. These two lines intersected at 20° C, lower below 20° C.According to Grodzinski, the ADMR is usually lower than RMR, but in our study the ADMR was found to be lower than the RMR only below 20° C, which suggests that the ambient temperature acts differently on ADMR and RMR. The temperature-dependent variation of both ADMR and RMR as well as their differences should be taken into account in the estimation of the productivity of animal population.


Quinolinic acid selectively induces apoptosis of human astrocytes: potential role in AIDS dementia complex.
There is evidence that the kynurenine pathway (KP) and particularly one of its end products, quinolinic acid (QUIN) play a role in the pathogenesis of several major neuroinflammatory diseases, and more particularly AIDS dementia complex (ADC). We hypothesized that QUIN may be involved in astrocyte apoptosis because: 1) apoptotic astrocytes have been observed in the brains of ADC patients, 2) ADC patients have elevated cerebrospinal fluid QUIN concentrations, and 3) QUIN can induce astrocyte death. Primary cultures of human fetal astrocytes were treated with three pathophysiological concentrations of QUIN. Numeration of apoptotic cells was assessed using double immunocytochemistry for expression of active caspase 3 and for nucleus condensation. We found that treatment of human astrocytes with QUIN induced morphological (cell body shrinking) and biochemical changes (nucleus condensation and over-expression of active caspase 3) of apoptosis. After 24 hours of treatment with QUIN 500 nM and 1200 nM respectively 10 and 14% of astrocytes were undergoing apoptosis. This would be expected to lead to a relative lack of trophic support factors with consequent neuronal dysfunction and possibly death. Astroglial apoptosis induced by QUIN provides another potential mechanism for the neurotoxicity of QUIN during ADC.


Low rate of detectable in utero transmission of Mycobacterium avium subspecies paratuberculosis in a dairy herd with a low prevalence of Johne's disease.
In an effort to correlate the likelihood of in utero transmission of Mycobacterium avium subsp. paratuberculosis (MAP), the causal organism of Johne's disease, with the test status of the dam, tissues from neonatal calves borne to known test status cows were cultured for the presence of MAP. Tissues from a single calf borne to a test-positive cow shedding large numbers of organisms in the feces were positive for MAP. The detected overall transmission rate was approximately 2% (1/49), and the detected transmission rate in cows that were fecal culture positive and serum enzyme-linked immunosorbent assay suspect or positive was approximately 4.3% (1/23).


Magnitude, Associated Risk Factors, and Trend Comparisons of Urinary Tract Infection among Pregnant Women and Diabetic Patients: A Systematic Review and Meta-Analysis.
Urinary tract infection (UTI) remains the most common bacterial infection that affects millions of people around the world, especially pregnant women (PW) and people with diabetes mellitus (DM). This systematic review and meta-analysis was aimed at finding the pooled prevalence of UTI and its associated risk factors among PW and DM patients. Scientific articles written in English were recovered from PubMed, ScienceDirect, Web of Science, Google Scholar, Cochrane Library, Google Engine, and University Library Databases. "Prevalence," "urinary tract infection," "associated factors," "pregnant women," "diabetic patients," and "Ethiopia" were search terms used for this study. For critical appraisal, PRISMA-2009 was applied. Heterogeneity and publication bias were evaluated using Cochran's Q, inverse variance (I2), and funnel plot asymmetry tests. A random effect model was used to calculate the pooled prevalence of UTI and its associated factors among both patients, along with the parallel odds ratio (OR) and 95% confidence interval (CI). For this meta-analysis, a total of 7271 participants were included in the 25 eligible studies. The pooled prevalence of UTI in Ethiopia among both patients was 14.50% (95% CI: 13.02, 15.97), of which 14.21% (95% CI: 12.18, 16.25) and 14.75% (95% CI: 12.58, 16.92) were cases of DM and PW, respectively. According to the subgroup analysis, the highest prevalence was observed in the Oromia region (19.84%) and in studies conducted from 2018 to 2022 (14.68%). Being female (AOR: 0.88, and 95% CI: 0.11, 1.65, P = 0.01) and having an income level ≤ 500ETB (AOR: 4.46, and 95% CI: -1.19, 10.12, P = 0.03) were risk factors significantly associated with UTI among patients with DM and PW, respectively. Furthermore, a history of catheterization (AOR = 5.58 and 95% CI: 1.35, 9.81, P < 0.01), urinary tract infection (AOR: 3.52, and 95% CI: 1.96, 5.08, P < 0.01), and symptomatic patients (AOR: 2.32, and 95% CI: 0.57, 4.06, P < 0.01) were significantly associated with UTI in both patients. Early diagnosis and appropriate medication are necessary for the treatment of UTI in patients with DM and PW.


Comparison of stroke care parameters in acute ischemic stroke patients with and without concurrent Covid-19. A Nationwide analysis.
Comparing health care parameters of acute ischemic stroke (AIS) patients with and without concurrent coronavirus disease 2019 (Covid-19, SARS-CoV-2 infection), may be helpful in terms of optimizing clinical and public health care during pandemic. We evaluated a nationwide administrative database of all hospitalized patients with main diagnosis of acute ischemic stroke with/without diagnosis of Covid-19 who were hospitalized during the time period from January 16th to May 15th, 2020. Data from a total of 1463 hospitals in Germany were included. We compared case numbers, treatment characteristics (intravenous thrombolysis, IVT; mechanical thrombectomy, MT; treated on an intensive care unit, stroke unit or regular ward) and in-hospital mortality of AIS with and without concurrent diagnosis of Covid-19. From a total of 30,864 hospitalized Covid-19 patients during the evaluation period in Germany, we identified a subgroup of 213 patients with primary diagnosis of AIS. Compared to the 68,700 AIS patients without Covid-19, this subgroup showed a similar rate of IVT (16.4% vs. 16.5%, p = 0.985) but a significantly lower rate of MT (3.8% vs. 7.9%, p = 0.017). In-hospital mortality rate was significantly higher in patients with AIS and concurrent Covid-19 compared to non-infected AIS patients (22.5% vs. 7.8%, p < 0.001). These nationwide data point out differences in mortality and medical treatment regime between AIS patients with and without concurrent Covid-19. Since the pandemic is still ongoing, these data draw attention to AIS as a less frequent but often fatal comorbidity in Covid-19 patients.


Modeling and optimal control applied to reduce the effects of greenhouse gases emitted from the coal-based power plant in Bangladesh.
The coal-fired power station is believed to be one of the major emitters of air pollutants, particularly carbon dioxide (CO2), which is the main sensitive driver of climate change due to global warming, consequently causing significant intimidation for the Sundarbans, the world's largest mangrove forest and nearby due to high emissions of air pollutants such as Carbon-Di-Oxide (CO2). Here, we used a compartmental mathematical model with 3 compartments to study the dynamics of greenhouse gas emissions, concentration, and uptake, which we can control by installing a chemical reactor system near the power plant and naturally afforesting the regions. The model was built from scratch to study these types of problems. First, we formulated the optimal control problem by connecting two control measurement systems: a chemical reactor system and natural afforestation. For this purpose, Pontryagin's maximum principle is used. The novelty of this work is the investigation of optimal strategies to minimize the impact of gases emitted by Coal based power plants on neighboring regions. More realistic facts such as system damage from excess emissions, most absorbers, and other facts are covered here. The numerical solution obtained illustrates the outcome of the system with initial values and theoretical parameters that best represent reality. By evaluating the performance index scores, and objective function values, we found that both controls (the chemical reactor system and natural afforestation) help minimize air pollution. We then simulated our model with 5 different control strategies to observe its performance in reducing pollutants. Once we determine that two control strategies are equally effective in reducing pollution, let's compare them by looking at the costs associated with each strategy. Therefore, using both control systems (chemical reactor and natural afforestation) with a higher reaction rate, we suggested chemical reactor system control as the best strategy.


[Vision screening in children: Review of the literature].
In children, refractive errors and amblyopia are the two most common causes of avoidable visual impairment. Screening for these is essential, especially since there is a so-called "sensitive" period during which the maturation of the visual pathways is not complete. The child's visual prognosis will therefore depend on his or her age, the duration of the visual deprivation and the timing of management. Visual screening is part of a public health approach, but there are significant regional disparities regarding its organization and the means used. We conducted a review of the literature in order to establish an inventory of available resources and improve practices.


Tests of two methods for identifying founder effects in metapopulations reveal substantial type II error.
Genetic analysis has been promoted as a way to reconstruct recent historical dynamics ("historical demography") by screening for signatures of events, such as bottlenecks, that disrupt equilibrium patterns of variation. Such analyses might also identify "metapopulation" processes like extinction and recolonization or source-sink dynamics, but this potential remains largely unrealized. Here we use simulations to test the ability of two currently used strategies to distinguish between a set of interconnected subpopulations (demes) that have undergone bottlenecks or extinction and recolonization events (metapopulation dynamics) from a set of static demes. The first strategy, decomposed pairwise regression, provides a holistic test for heterogeneity among demes in their patterns of isolation-by-distance. This method suffered from a type II error rate of 59-100 %, depending on parameter conditions. The second strategy tests for deviations from mutation-drift equilibrium on a deme-by-deme basis to identify sites likely to have experienced recent bottlenecks or founder effects. Although bottleneck tests have good statistical power for single populations with recent population declines, their validity in structured populations has been called into question, and they have not been tested in a metapopulation context with immigration (or colonization) and population recovery. Our simulations of hypothetical metapopulations show that population recovery can rapidly eliminate the statistical signature of a bottleneck, and that moderate levels of gene flow can generate a false signal of recent population growth for demes in equilibrium. Although we did not cover all possible metapopulation scenarios, the performance of the tests was disappointing. Our results indicate that these methods might often fail to identify population bottlenecks and founder effects if population recovery and/or gene flow are influential demographic features of the study system.


Effects of chronic social defeat stress on MAP kinase cascade.
Chronic psychological and social stress can cause psychiatric disorders in humans. In this study, we analyzed the mitogen-activated protein kinase (MAPK) cascade in the hippocampus of chronically socially defeated rats. The rats that were subjected to social defeat every day for 5 weeks showed physiological and behavioral changes, including a reduced rate of weight gain, enlarged adrenal glands, and increased immobility in the forced swim test without concomitant changes in locomotor activity in the open field test. Altered body weight and enlarged adrenal glands are typical symptoms of human depression. Prolonged immobility in the forced swim test indicates behavioral despair, a well-established index of depression. Because the MAPK cascade plays a pivotal role in depression, we quantified the expression of these molecules in the hippocampus of chronically defeated rats using western blot analysis. We found that phospho-MAPK kinases 1/2 (MEK1/2) and phospho-extracellular signal-regulated kinases 1/2 (ERK1/2) were decreased, whereas MAPK phosphatase-1 (MKP-1) was increased in the hippocampus of chronically defeated rats compared to the control group. These results were consistent with findings in depressed patients and other animal models of depression. In conclusion, our findings suggest that chronic psychosocial stress in Wistar rats induced depression-like behavior and downregulated the MAPK cascade in the hippocampus.


Affective Risk for Problem Drinking: Reciprocal Influences Among Negative Urgency, Affective Lability, and Rumination.
Affective disturbances have long been implicated in the onset and maintenance of problematic alcohol use. Affective risk theory for problem drinking has moved beyond early documentation that negative affect broadly confers risk to models specifying specific affectbased risk processes. This paper provides a theory-driven review of recent literature on the role of affect-based factors in the etiology of problematic alcohol use. First, we review recent advances in the understanding of affect-based risk for problem drinking. Second, we highlight the importance of three specific affect-based risk factors: urgency, affective lability, and rumination. Third, we offer hypotheses regarding the reciprocal relationships between specific risk factors and drinking problems. Finally, we suggest possible avenues for future research. Recent advances in the understanding of reciprocal prediction between affect-based risk factors and problem drinking have set the stage for important new avenues of investigation into the risk process. Affect-based risk processes appear to influence each otherover time, and they influence and are influenced by problem drinking. Further understanding of these processes will pave the way for a new generation of intervention strategies.


Synthesis of 1-hydroxy-3-O-substituted xanthone derivatives and their structure-activity relationship on acetylcholinesterase inhibitory effect.
This study focused on the synthesis of 1,3-dihydroxyxanthone (1) and its new derivatives with alkyl (2a-2f), alkenyl (2 g-2k), alkynyl (2 l-2n), and alkylated phenyl (2o-2r) groups at C3 position. The structures of these compounds were confirmed by MS, NMR, and FTIR spectroscopic data. All the substituted xanthones (2a-2r) showed significantly stronger acetylcholinesterase (AChE) inhibitory activities than 1. Compounds 2g and 2j exhibited the strongest activities with the IC50 values of 20.8 and 21.5 μM and their enzyme kinetic analyses indicated a mixed-mode inhibition. Molecular docking study revealed that 2g binds favourably to the active site of AChE via π-π stacking and hydrogen bonding from the xanthone ring, in addition to π-alkyl interaction from the substituent group. These xanthone derivatives are potential lead compounds to be further developed into Alzheimer's disease drugs.


Unusual case of ruptured sinus of Valsalva: rupture into left ventricle cavity along with distortion of mitral valve requiring double valve replacement.
We report a rare case of sinus of Valsalva aneurysm of left aortic sinus, which was bulging into left atrium (LA) distorting mitral valve and rupture into the left ventricle with severe aortic regurgitation in a 25 years old male patient. Due to the rupture, both aortic and mitral valves were irreparable and required a double valve replacement along with the closure of the neck of the aneurysmal cavity occupying the left atrial roof.


Phytochemicals for bacterial resistance--strengths, weaknesses and opportunities.
This review covers some of the opportunities which currently exist to exploit plants for their natural products as templates for new antibacterial substances. This is a timely exercise given the continuing and developing problems of bacterial resistance, and in particular multidrug-resistance (MDR). Some of the challenges which are evident with bacterial resistance will be described and the strengths and weaknesses of plant natural products are highlighted. Opportunities to characterise antibacterial compounds from several key taxa are described with activity against methicillin-resistant STAPHYLOCOCCUS AUREUS (MRSA), MDR variants of this species and MYCOBACTERIUM TUBERCULOSIS (MTB). These pathogens continue to cause problems in terms of their eradication and spread and MTB strains which are extremely-drug resistant (XDR) promise to afford an additional challenge for clinicians. The review also covers plant natural products that modulate or modify bacterial resistance. Specific examples include plant-derived efflux pump inhibitors (EPIs) which inhibit bacterial antibiotic efflux mechanisms that are problematic due to their broadness in substrate specificity. A summary on future trends and directions in this fruitful and interesting area is also given.


Cholesterol absorption and steroid excretion in cholesterol-fed guinea pigs.
Cholesterol absorption was studied in groups of guinea pigs fed diets containing 0, 0.1%, or 1% cholesterol. A similar proportion of tracer cholesterol was absorbed regardless of the cholesterol content of the diet. Furthermore, the proportion of tracer cholesterol absorbed by individual animals did not change when the cholesterol-free diet was changed to one containing 1% cholesterol. Cholesterol absorption was also measured in hyporesponding guinea pigs. These guinea pigs had been fed 1% cholesterol-containing diets for nearly a year with minimal pathological effects. These hyporesponders had a decreased intestinal transit time, which enabled them to decrease the fractional absorption of cholesterol below the levels seen in the controls, and to absorb less cholesterol/kg body weight than the hyperresponders. Excretion of total and of neutral steroids was measured in guinea pigs fed 0 or 1% cholesterol-containing diets. The 1% cholesterol-fed guinea pigs increased the excretion of steroids 3-fold over control levels. However, they absorbed more dietary cholesterol than they excreted in any form. It seems, therefore, that a major cause of the cholesterol pool expansion in the guinea pig is its inability to limit absorption of dietary cholesterol in conjunction with its inability to sufficiently increase excretion of steroids.


Communication: Microsecond dynamics of the protein and water affect electron transfer in a bacterial bc(1) complex.
Cross-membrane electron transport between cofactors localized in proteins of mitochondrial respiration and bacterial photosynthesis is the source of all biological energy. The statistics and dynamics of nuclear fluctuations in these protein/membrane/water heterogeneous systems are critical for their energetic efficiency. The results of 13 μs of atomistic molecular dynamics simulations of the membrane-bound bc1 bacterial complex are analyzed here. The reaction is affected by a broad spectrum of nuclear modes, with the slowest dynamics in the range of time-scales ∼0.1-1.6 μs contributing half of the reaction reorganization energy. Two reorganization energies are required to describe protein electron transfer due to dynamical arrest of protein conformations on the observation window. This mechanistic distinction allows significant lowering of activation barriers for reactions in proteins.


[Prophylaxis of venous thromboembolic disease in patients after the proximal femoral surgery].
Patients undergoing elective hip replacement and surgery for hip fracture are at increased risk of venous thromboembolic disease, a potentially preventable cause of mortality and morbidity. Although the association between these operations and venous thromboembolism has been recognized many years ago, there is still great variability in the clinical practices with respect to prophylaxis. This article aims to clarify the incidence and risk factors for deep venous thrombosis and pulmonary embolism after hip operations, and give evidence-based recommendations for prophylaxis adopted from the Seventh American College of Chest Physicians Conference (ACCP).


Localization and characterization of phosphorylation sites of the Fujinami avian sarcoma virus and PRCII virus transforming proteins.
Fujinami sarcoma virus (FSV) and PRCII are avian sarcoma viruses which share cellularly derived v-fps transforming sequences. The FSV P140gag-fps gene product is phosphorylated on three distinct tyrosine residues in transformed cells or in an in vitro kinase reaction. Three variants of FSV, and the related virus PRCII which lacks about half of the v-fps sequence found in FSV, encode gene products which are all phosphorylated at tyrosine residues contained within identical tryptic peptides. This indicates a stringent conservation of amino acid sequence at the tyrosine phosphorylation sites which presumably reflects the importance of these sites for the biologic activity of the transforming proteins. Under suitable conditions the proteolytic enzymes p15 and V8 protease each introduce one cut into FSV P140, p15 in the N-terminal gag-encoded region and V8 protease in the middle of the fps-encoded region. Using these enzymes we have mapped the major site of tyrosine phosphorylation to the C-terminal end of the fps region of FSV P140gag-fps. A second tyrosine phosphorylation site is found in the fps region of FSV P140 isolated from transformed cells, and a minor tyrosine phosphorylation site is found in the N-terminal gag-encoded region. Our results suggest that the C-terminal fps-encoded region is required for expression of the tyrosine-specific protein kinase activity.


From Pipettes to Science Policy.
Science policy provides PhD-trained scientists with unique and rewarding opportunities to support the research community. Careers in science policy require broad scientific knowledge coupled with keen problem-solving, data-analysis, and communication skills. This article describes strategies for scientists to engage in policy discussions, both extramural and full-time.


Suppressive competition: how sounds may cheat sight.
In this issue of Neuron, Iurilli et al. (2012) demonstrate that auditory cortex activation directly engages local GABAergic circuits in V1 to induce sound-driven hyperpolarizations in layer 2/3 and layer 6 pyramidal neurons. Thereby, sounds can directly suppress V1 activity and visual driven behavior.


Molecular mechanism for loss of visual cortical responsiveness following brief monocular deprivation.
A dramatic form of experience-dependent synaptic plasticity is revealed in visual cortex when one eye is temporarily deprived of vision during early postnatal life. Monocular deprivation (MD) alters synaptic transmission such that cortical neurons cease to respond to stimulation of the deprived eye, but how this occurs is poorly understood. Here we show in rat visual cortex that brief MD sets in motion the same molecular and functional changes as the experimental model of homosynaptic long-term depression (LTD), and that prior synaptic depression by MD occludes subsequent induction of LTD. The mechanisms of LTD, about which there is now a detailed understanding, therefore contribute to visual cortical plasticity.


Circulating Microvesicle-Associated Inducible Nitric Oxide Synthase Is a Novel Therapeutic Target to Treat Sepsis: Current Status and Future Considerations.
To determine whether mitigating the harmful effects of circulating microvesicle-associated inducible nitric oxide (MV-A iNOS) in vivo increases the survival of challenged mice in three different mouse models of sepsis, the ability of anti-MV-A iNOS monoclonal antibodies (mAbs) to rescue challenged mice was assessed using three different mouse models of sepsis. The vivarium of a research laboratory Balb/c mice were challenged with an LD80 dose of either lipopolysaccharide (LPS/endotoxin), TNFα, or MV-A iNOS and then treated at various times after the challenge with saline as control or with an anti-MV-A iNOS mAb as a potential immunotherapeutic to treat sepsis. Each group of mice was checked daily for survivors, and Kaplan-Meier survival curves were constructed. Five different murine anti-MV-A iNOS mAbs from our panel of 24 murine anti-MV-A iNOS mAbs were found to rescue some of the challenged mice. All five murine mAbs were used to genetically engineer humanized anti-MV-A iNOS mAbs by inserting the murine complementarity-determining regions (CDRs) into a human IgG1,kappa scaffold and expressing the humanized mAbs in CHO cells. Three humanized anti-MV-A iNOS mAbs were effective at rescuing mice from sepsis in three different animal models of sepsis. The effectiveness of the treatment was both time- and dose-dependent. Humanized anti-MV-A iNOS rHJ mAb could rescue up to 80% of the challenged animals if administered early and at a high dose. Our conclusions are that MV-A iNOS is a novel therapeutic target to treat sepsis; anti-MV-A iNOS mAbs can mitigate the harmful effects of MV-A iNOS; the neutralizing mAb's efficacy is both time- and dose-dependent; and a specifically targeted immunotherapeutic for MV-A iNOS could potentially save tens of thousands of lives annually and could result in improved antibiotic stewardship.


Contrasting effects of a convulsant (CHEB) and an anticonvulsant barbiturate (phenobarbitone) on amino acid release from rat brain slices.
The effects of a convulsant barbiturate, 5(2-cyclohexylidine-ethyl)-5-ethyl barbituric acid (CHEB), and phenobarbitone (PhB) on the release of exogenous D-aspartate and GABA from slices of rat cerebral cortex were investigated. While PhB inhibited potassium-evoked release of D-aspartate more so than that of GABA, CHEB potently inhibited potassium-evoked GABA release and stimulated evoked D-aspartate release, in a concentration-dependent manner. These actions are consistent with the observed in vivo convulsant and anticonvulsant properties of these barbiturates. CHEB, but not PhB also elevated spontaneous efflux of both amino acids. The actions of these barbiturates were further studied in calcium- and sodium-free media, and in the presence of tetrodotoxin and ruthenium red, agents known to alter ion flux across neuronal membranes. The results obtained indicate that different ionic mechanisms may be involved in the release of excitatory and inhibitory amino acid transmitters.


Kinematics of passive flexion following balanced and overstuffed fixed bearing unicondylar knee arthroplasty.
Progression of osteoarthritis in the unreplaced compartment following unicondylar knee arthroplasty (UKA) may be hastened if kinematics is disturbed following UKA implantation. The purpose of this study was to analyze tibiofemoral kinematics of the balanced and overstuffed UKA in comparison with the native knee during passive flexion since this is a common clinical assessment. Ten cadaveric knees were mounted to robotic manipulator and underwent passive flexion from 0 to 90°. The kinematic pathway was recorded in the native knee and in the balanced, fixed bearing UKA. The medial UKA was implanted using a measured resection technique. Additionally, a one millimeter thicker tibial insert was installed to simulate the effects of overstuffing. Tibial kinematics in relation to the femur was recorded. Following UKA the tibia was externally rotated, and in valgus relative to the native knee near extension. In flexion, installing the UKA caused the knee to be translated medially and anteriorly. The tibia was translated distally through the entire range of flexion after UKA. Compared to the balanced UKA, overstuffing further increased valgus at full extension and distal translation of the tibia from full extension to 45° flexion. UKA implantation altered tibiofemoral kinematics in all planes. Differences were small; nevertheless, they may affect tibiofemoral loading patterns. Alterations in tibiofemoral kinematics following UKA might have implications for prosthesis failure and progression of osteoarthritis in the remaining compartment. Overstuffing should be avoided as it further increased valgus and did not improve the remaining kinematics.


Biohybrid Adsorbent for the Preconcentration of Lead and Its Determination in Fruit Juices by Electrothermal Atomic Absorption Spectrometry.
Fruit juices are one of the most non-alcoholic beverages consumed in the world. Essential elements and other nutrients present in fruit juices play an important role in human well-being. However, fruit juices may also contain potentially toxic elements at trace levels, causing health risks. The objective of this work was to develop an analytical methodology based on the preconcentration of lead using a new biodegradable hybrid material (BHM) composed of Rhodococcus erythropolis AW3 bacteria and Brassica napus hairy roots. The BHM was implemented in an online solid-phase extraction (SPE) system for the determination of lead in fruit juices by electrothermal atomic absorption spectrometry (ETAAS). Effects of critical parameters on lead retention were studied. Under optimal experimental conditions, extraction efficiency higher than 99.9% and an enrichment factor of 62.5 were achieved. The dynamic capacity of the BHM was 36 mg/g, which favored the reuse of the column for at least eight biosorption-desorption cycles. The LOD and LOQ for preconcentration of 5 mL of sample were 5.0 and 16.5 ng/L lead, respectively. The RSD was 4.8% (at 1 µg/L lead and n = 10). The developed method was suitable for application to lead determination in different types of fruit juice. A novel microextraction procedure based on the use of a biohybrid adsorbent. Highly sensitive determination of Pb at trace levels. Analysis of Pb in fruit juices samples. An eco-friendly microextraction technique for Pb determination.


Chromosome-level organization of the regulatory genome in the Drosophila nervous system.
Previous studies have identified topologically associating domains (TADs) as basic units of genome organization. We present evidence of a previously unreported level of genome folding, where distant TAD pairs, megabases apart, interact to form meta-domains. Within meta-domains, gene promoters and structural intergenic elements present in distant TADs are specifically paired. The associated genes encode neuronal determinants, including those engaged in axonal guidance and adhesion. These long-range associations occur in a large fraction of neurons but support transcription in only a subset of neurons. Meta-domains are formed by diverse transcription factors that are able to pair over long and flexible distances. We present evidence that two such factors, GAF and CTCF, play direct roles in this process. The relative simplicity of higher-order meta-domain interactions in Drosophila, compared with those previously described in mammals, allowed the demonstration that genomes can fold into highly specialized cell-type-specific scaffolds that enable megabase-scale regulatory associations.


Heterogeneity of neutralization-related epitopes within a bluetongue virus serotype.
Twenty-four monoclonal antibodies raised against a 1962 Wyoming isolate of blue-tongue virus serotype 17 (BTV 17) were tested against 20 other field isolates of this serotype in a solid-phase radioimmunoassay (RIA), neutralization, and mouse passive protection tests. Of the 21 antibodies that bound in RIA to acetone-fixed BTV-infected cells, 18 bound to cells infected with any of the BTV 17 isolates and 3 detected minor antigenic differences in two isolates. The remaining 3 antibodies, that bound in RIA only to unfixed virus-infected cells detected additional differences. Of the 3 antibodies binding to unfixed virus-infected cells one bound to all but 2 isolates. A second antibody, 6C3A.2, bound only to the Wyoming isolate and passively protected mice against this isolate. The third antibody, 6C2A.4.2, bound to the Wyoming isolate and to 8 isolates from the mid-South U. S., but not to 12 isolates from California. Antibody 6C2A.4.2 neutralized the Wyoming and mid-South isolates to which it bound and passively protected mice against the Wyoming isolate but provided little or no protection against 4 California isolates tested. Polyclonal serum from mice immunized against Wyoming BTV 17 bound in RIA to all BTV 17 isolates and neutralized all isolates. Thus, three neutralization-related antigenic determinants were disclosed, one (perhaps a set) recognized by immune sera on all BTV 17 isolates, a second recognized by antibody 6C2A.4.2 on the Wyoming and 8 mid-South isolates, and a third recognized by antibody 6C3A.2 only on the Wyoming isolate. These differences may be important in selection of virus strains for vaccine development.


Molecular cloning and functional analysis of chitinases in the fresh water snail, Lymnaea stagnalis.
Molluscan shells, consisting of calcium carbonate, are typical examples of biominerals. The small amount of organic matrices containing chitin and proteins in molluscan shells regulates calcification to produce elaborate microstructures. The shells of gastropods have a spiral shape around a central axis. The shell thickness on the internal side of the spiral becomes thinner than that on the outer side of the spiral during the growth to expand the interior space. These observations suggest that a dissolution process works as a remodeling mechanism to change shell shape in molluscan shells. To reveal the dissolution mechanism involved in the remodeling of gastropod spiral shells, we focused on chitinases in the fresh water snail Lymnaea stagnalis. Chitinase activity was observed in the acetic acid-soluble fraction of the shell and in the buffer extract from the mantle. Allosamidin, a specific inhibitor of family 18 chitinases, inhibited the chitinase activity of both fractions completely. Homology cloning and transcriptome analyses of the mantle revealed five genes (chi-I, chi-II, chi-III, chi-IV, and chi-V) encoding family 18 chitinases. All chitinases were expressed in the mantle and in other tissues suggesting that chitinases in the mantle have multiple-functions. Treatment with commercially available chitinase obtained from Trichoderma viride altered the shell microstructure of L. stagnalis. Larvae of L. stagnalis cultured in allosamidin solution had a thinner organic layer on the shell surface. These results suggest that the chitinase activities in the shell and mantle are probably associated with the shell formation process.


Cross neutralization of SARS-CoV-2 omicron subvariants after repeated doses of COVID-19 mRNA vaccines.
We have measured the humoral response to messenger RNA (mRNA) vaccines in COVID-19 naïve and convalescent individuals. Third doses of mRNA COVID-19 vaccines induced a significant increase in potency and breadth of neutralization against SARS-CoV-2 variants of concern (VoC) including Omicron subvariants BA.1, BA.2, and BA.2.12.1, that were cross-neutralized at comparable levels and less for BA.4/5. This booster effect was especially important in naïve individuals that only after the third dose achieved a level that was comparable with that of vaccinated COVID-19 convalescents except for BA.4/5. Avidity of RBD-binding antibodies was also significantly increased in naïve individuals after the third dose, indicating an association between affinity maturation and cross neutralization of VoC. These results suggest that at least three antigenic stimuli by infection or vaccination with ancestral SARS-CoV-2 sequences are required to induce high avidity cross-neutralizing antibodies. Nevertheless, the circulation of new subvariants such as BA.4/5 with partial resistance to neutralization will have to be closely monitored and eventually consider for future vaccine developments.


Formal total synthesis of (+/-)-vindoline by tandem radical cyclization.
A formal total synthesis of (+/-)-vindoline 1 has been achieved featuring the tandem cyclization of radicals produced from the iodoaryl azide 19a.


A premature referral to the mortuary. Cerebral recovery with barbiturate therapy.
The authors report a patient in circulatory arrest with unusual spontaneous cardiopulmonary recovery in the mortuary. Cerebral outcome and clinical evaluation of various therapeutic modalities in postischemic encephalopathy are discussed briefly.


Urinary aldosterone-to-active-renin ratio: a useful tool for predicting resolution of hypertension after adrenalectomy in patients with aldosterone-producing adenomas.
The purpose of this study was to determine the preoperative clinical and biological factors that predict the clinical outcomes after surgery, in subjects with aldosterone-producing adenomas (APAs). Fifty-eight patients (mean age 52 +/- 11 years) with APA were followed up for 43 +/- 13 months after they had undergone unilateral adrenalectomy. The subjects were classified as "cured" (n = 23) if the blood pressure (BP) was <140/90 mm Hg without postoperative medication, "normalized" (n = 20) if BP was <140/90 mm Hg with antihypertensive therapy, and "uncontrolled" (n = 15) if a BP of < or =140/90 mm Hg was not achieved despite intensive therapy. The cured patients had a significantly lower mean preoperative age, cardiac mass, and serum creatinine (P < 0.001) than the other subjects. The main independent predictors of surgical curability were: age (P < 0.01), low serum potassium (P < 0.0001), and the urinary aldosterone-to-active-renin (UAAR) ratio (P < 0.008). Among the hormonal parameters, the UAAR ratio provided the best area under the receiver operating-characteristics curve (0.802 (confidence interval (CI) 95%: 0.676-0.944)). For a cutoff value of 15, the positive and negative predictive values of the UAAR ratio were 85 and 92%, respectively. In the study population as a whole, surgical treatment restored the age-systolic BP (SBP) relationship (P < 0.006), which was insignificant before surgery. Although all the subjects showed lowering of BP after surgery, and the age-BP relationship was restored, the long-term cure rate of APA subjects was 40%. The UAAR ratio, by comparison with other classical hormonal features of primary aldosteronism, was the best independent predictor of the cure of hypertension after adrenalectomy.


Intestinal FGF15/19 physiologically repress hepatic lipogenesis in the late fed-state by activating SHP and DNMT3A.
Hepatic lipogenesis is normally tightly regulated but is aberrantly elevated in obesity. Fibroblast Growth Factor-15/19 (mouse FGF15, human FGF19) are bile acid-induced late fed-state gut hormones that decrease hepatic lipid levels by unclear mechanisms. We show that FGF15/19 and FGF15/19-activated Small Heterodimer Partner (SHP/NR0B2) have a role in transcriptional repression of lipogenesis. Comparative genomic analyses reveal that most of the SHP cistrome, including lipogenic genes repressed by FGF19, have overlapping CpG islands. FGF19 treatment or SHP overexpression in mice inhibits lipogenesis in a DNA methyltransferase-3a (DNMT3A)-dependent manner. FGF19-mediated activation of SHP via phosphorylation recruits DNMT3A to lipogenic genes, leading to epigenetic repression via DNA methylation. In non-alcoholic fatty liver disease (NAFLD) patients and obese mice, occupancy of SHP and DNMT3A and DNA methylation at lipogenic genes are low, with elevated gene expression. In conclusion, FGF15/19 represses hepatic lipogenesis by activating SHP and DNMT3A physiologically, which is likely dysregulated in NAFLD.


The D-domain of Sp3 modulates its protein levels and activation of the p21(CIP1/WAF1) promoter.
A variety of signals result in the transcriptional induction of the p21(CIP1/WAF1) promoter and both Sp1 and the related Sp3 proteins have been implicated in this induction. We have characterized the role of the C-terminal D-domains of both Sp1 and Sp3 proteins in the activation of this promoter in response to butyrate treatment of Hep G2 cells. We have defined a negative regulatory domain present in the C-terminus of Sp3. This domain decreases Sp3 protein levels, and this property can be transferred to Sp1. Changes in Sp3 protein levels may bring about growth arrest through the induction of inhibitors of the cell cycle such as p21(CIP1/WAF1).


PhI(OCOCF3)2-mediated C-C bond formation concomitant with a 1,2-aryl shift in a metal-free synthesis of 3-arylquinolin-2-ones.
The reaction of the readily available N-methyl-N-phenylcinnamamides with phenyliodine bis(trifluoroacetate) (PIFA) in the presence of Lewis acids provides a general and efficient assembly of a variety of 3-arylquinolin-2-one compounds. This novel approach features not only metal-free oxidative C(sp(2))-C(sp(2)) bond formation but also an exclusive 1,2-aryl migration.


Patterns of complementary therapy use by homebound cancer patients in Taiwan.
This study explores the use of complementary therapy and factors associated with the use of such therapies by cancer patients in Taiwan who were receiving surgery, chemotherapy, or radiotherapy and lived at home. Data were collected by purposive sampling and analyzed by chi-square testing. Subjects (N = 137) from two Taipei area hospital-based oncology centers were interviewed by using a structured questionnaire. Sixty percent of the total sample used complementary therapies. Variables, such as gender, duration of illness, diagnostic stages, chemotherapy, and symptoms distress, were significantly (p <.05) related to the use of complementary therapies. Western health professionals need to know what complementary therapies their clients are using so that they can respond appropriately to questions raised by their clients, as well as help them to acknowledge diverse kinds of treatment in their therapeutic plans.


Spatiotemporal variations in childhood lymphoma cancer incidence and its survival rate in Iran, 2005-2015: a cross-sectional study.
Childhood lymphoma is the second leading cause of cancer in children under 15 years of age in Iran. The aim of this study was to investigate the spatial and time variations in lymphoma incidence as well as the children's survival time in Iran. This cross-sectional study was conducted using lymphoma cases (children under 14 years of age) from 2005 to 2015, and the data were obtained from the National Cancer Registry Center. The frequency, age-standardised incidence rate (ASIR), spatial clustering in national level and the survival rate (1 year and 5 years) using Kaplan-Meier method were evaluated. We used Spatial and Temporal Scan statistics software in order to detect statistically significant clusters in spatial analysis. A total number of 746 girls and 1610 boys were diagnosed with lymphoma during a 10-year period. ASIRs (per 100 000 people) for girls ranged from 0 in Ilam to 3.47 in Yasuj, and it ranged from 0.19 in Ilam to 5.91 in Yazd for boys from 2005 to 2015. Spatial analysis result showed a large statistically significant cluster (the most likely cluster) for both boys (relative risk (RR)=2.37) and girls (RR=2.49) located in the northwest of Iran. Fortunately, survival rate for both boys and girls was over 95.5%. Lymphoma incidence rates had heterogeneous geographical distribution, and some significant clusters were identified which strengthens the role of possible aetiological factors, and further studies are needed to clarify this ambiguity. Fortunately, the survival rate of this cancer in Iran was good and it was similar to the high-income countries.


Bicycle helmet use among children in the United States: the effects of legislation, personal and household factors.
Children ages 5-14 years have the highest rate of bicycle-related injuries in the country. Bicycle helmets can prevent head and brain injuries, which represent the most serious type of bicycle-related injury. This paper compares children's bicycle helmet use to that estimated from an earlier study, and explores regional differences in helmet use by existing helmet legislation. This study was a cross-sectional, list-assisted random-digit-dial telephone survey. Interviews were completed by 9,684 respondents during 2001-2003. The subset with at least one child in the household age 5-14 years (2,409 respondents) answered questions about bicycle helmet use for a randomly selected child in their household. Almost half (48%) of the children always wore their helmet, 23% sometimes wore their helmet, and 29% never wore their helmet. Helmet wearing was significantly associated with race, ethnicity, and child age but was not associated with the sex of the child. Other significant predictors of use included household income, household education, census region, and bicycle helmet law status. Statewide laws were more effective than laws covering smaller areas. The proportion of children who always wore a helmet increased from 25% in 1994 to 48% in 2001-2002. Significant increases in helmet use from 20% to 26% were seen among both sexes, younger (5-9 years) and older (10-14 years) children, and in all four regions of the country. While there has been substantial progress in the number of children who always wear their helmets, more than half do not. Further progress will require using a combination of methods that have been shown to successfully promote consistent helmet use. minimal.


The RABBIT risk-based approach to clinical implementation of new technology: SRS as a case study.
Radiation oncology technology continues to evolve rapidly, resulting in advanced versions frequently being brought to market. Before a new product is used standard tests are carried out to reduce the risks associated with failure of the equipment to comply with well-established technical specifications. It is much harder to identify and reduce the risks associated with how the new technology is used clinically, such as those related to poor communication and high workload. To ensure that new technology and techniques are used safely and appropriately the implementation project should be managed by a multidisciplinary team (MDT) made up of representatives from all the relevant professions. The MDT's role is to agree on the project scope, identify and rank all risks and benefits, and direct resources towards mitigating the highest risks. Before clinical release there should be consensus from the MDT that the benefits of the new technology outweigh the residual risks. The introduction of initiatives to optimise current practice may involve major changes which can be met with barriers such as limited support from management, insufficient time for MDT meetings, and staff fearful of being shown to have poor practices. To help overcome these challenges our team at St George Hospital Cancer Care Centre has developed a Risk and Benefit Balance Impact Template (RABBIT), which guides an MDT through the rapid implementation and safe use of new technology and techniques with an easy to follow Microsoft Word document. The implementation of stereotactic radiosurgery is used as a case study to illustrate the RABBIT methodology. The RABBIT is a user-friendly method for a busy radiotherapy clinic to transition to a risk-based MDT approach for the implementation of new technologies and techniques. When staff from all disciplines feel empowered to raise concerns about risks the workplace become inherently safer for patients and staff alike.


Some blood vessels in the rat median eminence are surrounded by a dense plexus of vasoactive intestinal polypeptide/peptide histidine isoleucine (VIP/PHI) immunoreactive nerves.
Using immunohistochemistry at the light and electron microscopic level some blood vessels along the median eminence were shown to be surrounded by dense networks of vasoactive intestinal polypeptide/peptide histidine isoleucine (VIP/PHI)-positive fibers. VIP and PHI released from these fibers may contribute to the elevated levels of these two peptides measured in portal blood as compared to peripheral blood by radioimmunoassay. VIP and PHI may also be important in the control of blood flow through the median eminence.


Experimental study on temperature rise of acoustic radiation force elastography.
Acoustic radiation force (ARF) elastography is potentially useful for imaging the elasticity of human tissue. Because a "push wave" that is used to generate ARF is a long burst wave comparable to that used in regular clinical imaging, detailed investigation of its safety is required. We focus on the transient temperature rise in the far field, where the beam paths are overlapped. Soft tissue mimicking a phantom and bone samples were exposed to a 2-MHz plane wave for 20 s. The temperature rises in the far field were measured using a thermocouple. The temperature rises at 1 ms, the time required for the displacement measurement, were estimated by fitting the experimental results. The results showed that the thermosensitivity of the bone was 36 times higher than that of the phantom, and the use of a repeated push wave may have exceeded the allowable maximum temperature rise, 1°C, on the bone surface. In conclusion, the imaging area, including the path of the push wave, should be carefully checked and the time interval for consecutive use should be adjusted to prevent thermal risk on the surface of the bone.


The enteric metabolite, propionic acid, impairs social behavior and increases anxiety in a rodent ASD model: Examining sex differences and the influence of the estrous cycle.
Research suggests that certain gut and dietary factors may worsen behavioral features of autism spectrum disorder (ASD). Treatment with propionic acid (PPA) has been found to create both brain and behavioral responses in rats that are characteristic of ASD in humans. A consistent male bias in human ASD prevalence has been observed, and several sex-differential genetic and hormonal factors have been suggested to contribute to this bias. The majority of PPA studies in relation to ASD focus on male subjects; research examining the effects of PPA in females is scarce. The present study includes two experiments. Experiment 1 explored sex differences in the effects of systemic administration of PPA (500 mg/kg, ip) on adult rodent social behavior and anxiety (light-dark test). Experiment 2 investigated differential effects of systemic administration of PPA (500 mg/kg) on social behavior and anxiety in relation to fluctuating estrogen and progesterone levels during the adult rodent estrous cycle. PPA treatment impaired social behavior and increased anxiety in females to the same degree in comparison to PPA-treated males. As well, females treated with PPA in their diestrus phase did not differ significantly in comparison to females administered PPA in their proestrus phase, in terms of reduced social behavior and increased anxiety.


Erratum: The effects of systematic psychological nursing on the sleep quality of schizophrenic patients with sleep disorders.
[This corrects the article on p. 7263 in vol. 13, PMID: 34306491.].


microRNA-143-3p contributes to inflammatory reactions by targeting FOSL2 in PBMCs from patients with autoimmune diabetes mellitus.
Autoimmune diabetes mellitus (defined as ADM) comprises classical type 1 diabetes mellitus (T1DM) and latent autoimmune diabetes in adults (LADA). In this study, microRNAs (miRNAs) expression profiles and functions in peripheral blood mononuclear cells (PBMCs) of ADM patients were mapped and used to explore epigenetic regulation of the pathogenesis of ADM. PBMCs samples from T1DM patients, LADA patients, and type 2 diabetes mellitus (T2DM) patients, as well as age- and sex-matched healthy controls for T1DM and T2DM, respectively, were collected and were sequenced to screen the miRNAs expression profiles. The target genes were verified by dual-luciferase reporter assay. Silencing or overexpressing of the differentially expressed miRNAs, or simultaneously silencing the miRNAs and it's target gene, and then levels of the mRNAs, protein and cytokines were detected. miR-143-3p expression was upregulated in ADM patients. The target gene of miR-143-3p was identified as Fos-related antigen 2 (FOSL2). Transfection of a miR-143-3p inhibitor into PBMCs upregulated FOSL2 expression, resulting in a downregulated expression of the IL-2, TNF-α, and IFN-γ, and an upregulated expression of IL-6. Transfection of a miR-143-3p mimic into PBMCs downregulated FOSL2 expression, leading to an upregulation of IL-2 and TNF-α expression and a downregulation of IL-6 expression. When silencing FOSL2 while inhibiting miR-143-3p in PBMCs, there was no significant change in expression of the FOSL2 mRNA, protein and cytokines. The expression of miR-143-3p in PBMCs from ADM patients is upregulated. miR-143-3p could function in the pathogenesis of ADM by modulating the inflammatory reaction through FOSL2.


Optimization of the 4-aryl group of 4-aryl-pyridine glucagon antagonists: development of an efficient, alternative synthesis.
A narrow structure-activity relationship was established for the 4-aryl group in 4-aryl-pyridine glucagon antagonists, with only small substituents being well-tolerated, and only at the 3'- and 4'-positions. However, substitution with a 2'-hydroxy group gave a ca. 3-fold increase in activity (e.g., 4'-fluoro-2'-hydroxy analogue 33, IC50=190 nM). For efficient preparation of 2'-substituted phenylpyridines, a novel synthesis via pyrones and 4-methoxy-pyridines was developed.


Protecting short-term intravascular ear catheters in healthy rabbits.
Researchers may place a catheter in the ear vessel of a rabbit for a short period of time in order to collect repeated blood samples without extensive restraint of the animal. Maintaining such a catheter in a healthy rabbit can be challenging, as the animal may scratch at the ear, removing the catheter or forming a large hematoma that might impede blood sampling. The authors developed a technique for protecting the indwelling catheter by cutting a section of moleskin to the same shape as the ear and gluing it to the surface of the ear and the catheter. They applied this technique to collect multiple blood samples during 12-h periods from nine rabbits in a pharmacokinetics study. Catheters remained patent in five rabbits for 12 h, in two rabbits for 8 h, in one rabbit for 6 h and in one rabbit for 4 h. This technique allowed for collection of repeated blood samples and prevented the rabbits from interfering with the catheter while allowing them to move freely during the sampling period.


The effect of back-transplants of the embryonic gut wall on growth of the neural tube.
Experiments in which the developing gut of avian embryos was back-transplanted to permit the bowel to interact with the developing neural tube were undertaken. Segments of intestine from 4-day quail embryos were implanted between the somites and neural tubes of chick embryos of 7 to 24 somites. The spinal cord responded to the presence of the bowel by enlarging unilaterally on the side of the graft. This effect encompassed both gray and white matter and was accompanied by the extension of neuritic projections from the spinal cord into the enteric grafts. The growth-promoting effect of enteric transplants was manifest at all levels of the neural tube where the grafts were made and led to enlargement of the brain as well as the spinal cord; however, truncal neural crest derivatives in the region of the grafts, such as developing sympathetic and spinal ganglia, were unaffected. Neither sham operations nor grafts of ciliary ganglion, lung, pancreas, mesonephros, or rudiment of the eye mimicked the action of the gut. The effect of the bowel was manifest as early as 24 hr following back-transplantation and was found to be due to an increase in the number of cells in the neuroepithelium. The cell responsible for the ability of the gut wall to enhance neuroepithelial proliferation was not identified, but the effect lacked species specificity and could be elicited in the absence of endoderm or neural crest derivatives in the explant. We propose that the musculoconnective tissue of the gut produces a short-range diffusible factor that induces mitogenic activity in the neuroepithelial cells of the neural tube, but not in the crest cells that form sympathetic or sensory ganglia. Since the gut is not normally in apposition to the neural tube, we suggest that the physiological targets of this factor are the specialized crest cells that colonize the bowel and give rise to the enteric nervous system.


Diagnosis, management, and outcomes of venous thromboembolism in COVID-19 positive patients: a role for direct anticoagulants?
Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of thromboembolic complications due to systemic coagulation activation. Little is known about the role of direct anticoagulants (DOACs) in COVID-19 related thrombosis. In this audit we sought to distinguish COVID-19 hospitalised patients with a diagnosis of venous thromboembolism (VTE) and record their outcomes over a period of 3 months (01/02/2020-30/04/2020). A total of 1583 patients were diagnosed with laboratory proven COVID-19 disease. Amongst them, 38 patients (0.82%) suffered VTE (median age 68 years, male/female: 20/18). VTE was the presenting symptom on admission in 71%. Pulmonary embolism was diagnosed in 92% of patients; 5 patients required intensive care and 3 underwent thrombolysis. 27 patients received initial treatment with unfractionated heparin/low molecular weight heparin (LMWH) while 10 were treated with direct anticoagulants (DOACs). After a median follow up of 25 days, 29 (76%) patients were alive while 5 were still hospitalised. Most patients (83%) were discharged on DOACs, no VTE recurrence or bleeding was recorded post-discharge. Our results suggest that direct anticoagulants could be a safe and effective treatment option in selected COVID-19 positive patients who have suffered venous thromboembolism.


A pilot, prospective trial of IntuBrite® versus Macintosh direct laryngoscopy for paramedic endotracheal intubation in out of hospital cardiac arrest.
Intubation in the case of out-of-hospital cardiac arrest (OHCA) is one of the most difficult procedures for Emergency Medical Services (EMS). The use of a laryngoscope with a dual light source is an interesting alternative to classic laryngoscopes. However, there are as yet no prospective data concerning the use of double light direct laryngoscopy (DL) by paramedics in traditional ground ambulance agencies in OHCA. We performed a non-blinded trial in a single EMS in Poland within ambulances crews, comparing time and first pass success (FPS) for endotracheal intubation (ETI) in DL using the IntuBrite® (INT) and Macintosh laryngoscope (MCL) during cardiopulmonary resuscitation (CPR). We collected both patient and provider demographic information along with intubation details. The time and success rates were compared using an intention-to-treat analysis. Over a period of 40 months, a total of 86 intubations were performed using 42 INT and 44 MCL based on an intention-to-treat analysis. The FPS time of the ETI attempt (13.49 vs. 15.55 s) using an INT which was shorter than MCL was used (p < 0.05). First attempt success (34/42, 80.9% vs. 29/44, 64.4%) was comparable for INT and MCL with no statistical significance. We found a statistically significant difference in intubation attempt time when the INT laryngoscope was used. Intubation first attempt success rates with INT and MCL were comparable with no statistical significance during CPR performed by paramedics. Trial was registered in Clinical Trials: NCT05607836 (10/28/2022).


The regulation of polyclonal immunoglobulin synthesis by FcR+ and FcR- monocyte subsets.
FcR+ and FcR- monocyte subsets were added to the pokeweed mitogen (PWM) or Staphylococcus aureus Cowan I-stimulated cultures of peripheral blood mononuclear cells (PBMC) or to PBMC depleted of monocytes. The numbers of immunoglobulin-secreting cells (ISC) and cells with intracytoplasmic immunoglobulins (PC) were evaluated 6 days later. The addition of FcR- subset increased the number of ISC in cultures of PBMC stimulated with PWM and reconstituted the response of monocyte depleted PBMC. In contrast, FcR+ monocytes suppressed PWM-induced response and, when added in high dose, also that induced by S. aureus. The FcR+ monocytes suppressed the response by inhibition of immunoglobulin secretion but not the development of PC. This suggests that FcR+ monocytes may modulate humoral response by preferential inhibition of the final differentiation of B lymphocytes into ISC.


Risk of unprovoked seizure after acute symptomatic seizure: effect of status epilepticus.
We asked whether acute symptomatic status epilepticus (SE) increases the risk for subsequent unprovoked seizure compared with less prolonged acute symptomatic seizure. We also explored whether the risk of unprovoked seizure differs by cause. We ascertained all first episodes of acute symptomatic seizure among residents of Rochester, Minnesota, through the Rochester Project's records-linkage system. Information was collected on seizure duration, age, sex, cause, and subsequent unprovoked seizure. At 10 years of follow-up, the risk of unprovoked seizure was 41% for those with acute symptomatic seizure with SE and 13% for those without SE. Controlling for age, sex, and cause, SE increased the risk for subsequent unprovoked seizure 3.3-fold (95% confidence interval, 1.8-6.1) compared with brief acute symptomatic seizures. Among patients with SE, the risk of unprovoked seizure was increased 18.8-fold for patients with anoxic encephalopathy, 7.1-fold for patients with a structural cause, 3.6-fold for patients with a metabolic cause. The increased risk for unprovoked seizure after SE compared with shorter seizures may be due to SE being a marker for severity of injury, damage caused by SE, or a biological substrate associated with the tendency to experience SE.


Contribution of platelet CX(3)CR1 to platelet-monocyte complex formation and vascular recruitment during hyperlipidemia.
The chemokine receptor CX(3)CR1 is an inflammatory mediator in vascular diseases. On platelets, its ligation with fractalkine (CX(3)CL1) induces platelet activation followed by leukocyte recruitment to activated endothelium. Here, we evaluated the expression and role of platelet-CX(3)CR1 during hyperlipidemia and vascular injury. The existence of CX(3)CR1 on platelets at mRNA and protein level was analyzed by RT-PCR, quantitative (q)PCR, FACS analysis, and Western blot. Elevated CX(3)CR1 expression was detected on human platelets after activation and, along with increased binding of CX(3)CL1, platelet CX(3)CR1 was also involved in the formation of platelet-monocyte complexes. Interestingly, the expression of CX(3)CR1 was elevated on platelets from hyperlipidemic mice. Accordingly, CX(3)CL1-binding and the number of circulating platelet-monocyte complexes were increased. In addition, CX(3)CR1 supported monocyte arrest on inflamed smooth muscle cells in vitro, whereas CX(3)CR1-deficient platelets showed decreased adhesion to the denuded vessel wall in vivo. Platelets in hyperlipidemic mice display increased CX(3)CR1-expression and assemble with circulating monocytes. The formation of platelet-monocyte complexes and the detection of platelet-bound CX(3)CL1 on inflamed smooth muscle cells suggest a significant involvement of the CX(3)CL1-CX(3)CR1 axis in platelet accumulation and monocyte recruitment at sites of arterial injury in atherosclerosis.


Can hyperimmune anti-CMV globulin substitute for convalescent plasma for treatment of COVID-19?
Information on treatment of COVID-19 infection in renal transplant recipients is scarce, especially in symptomatic patients and patients with recent major clinical events. This group of patients suffers from different opportunistic infections which may coexist with COVID-19. Currently available expert opinions suggest reduction of immunosuppression therapy for renal transplant recipients with symptomatic COVID-19 infection with either antiviral drugs, hydroxychloroquine and/or azithromycin. Inspired by our experience in treatment of CMV pneumonia and literature data on the potential benefit of convalescent plasma for treatment of different viral diseases we suggest use of the hyperimmune anti-CMV gamma globulins in addition to other available therapies. Besides the immunosuppression reduction which is supposed to be beneficial, immunoglobulins with their immunomodulatory effects and possible antiviral role, may increase a possibility for favorable outcome.


Effects of vagotomy on hypoglossal and phrenic responses to hypercapnia in the decerebrate rat.
Hypercapnia characterizes a variety of physiological and pathological states and must be compensated effectively by the respiratory, cardiovascular, renal, and intra- and extracellular pH buffering systems to maintain homeostasis. Several studies have examined the respiratory response to hypercapnia, but contemporaneous changes in respiratory frequency and tidal volume prevent investigating the pure influence on respiratory amplitude. Therefore, we sought to test the effect of hypercapnia on hypoglossal (XII) and phrenic nerve (PN) inspiratory (Insp) and XII pre-inspiratory (pre-I) activities in vagus-intact and vagus-denervated animals. Experiments were performed on six artificially-ventilated unanesthetized pre-collicular decerebrate Sprague-Dawley adult male rats. Vagotomy under normocapnic conditions effected the consistent appearance of significant XII pre-I and a greater increase in XII than PN Insp amplitude. In the vagus-intact state, administration of a hypercapnic (5% CO2, 95% O2) gas mixture resulted in a greater increase in XII than PN Insp activity. In the vagotomized state, hypercapnia caused a drastic increase in XII pre-I and significant non-differential increases in both XII and PN Insp activity. The increase in XII pre-I was significantly greater than hypercapnia-induced increases in XII and PN Insp discharges. Following vagotomy, duration and amplitude of XII pre-I are potently modulated by CO2 tension. Based on our results, we conclude that vagal afferents exert differential inhibition of PN Insp and XII pre-I/Insp motor outputs. The role of vagal control in orchestration and optimization of respiratory response to hypercapnia is discussed.


Synthesis and biological evaluation of 3-arylisoquinolines as antitumor agents.
To investigate the structure-activity relationship of 7,8-dimethoxy-2- methyl-3-(4,5-methylenedioxy-2-vinylphenyl)isoquinolin-1(2H) -one 2, diverse substituted 3-arylisoquinolines were synthesized and tested in vitro antitumor activity against five human tumor cell lines. The results showed a broad antitumor spectrum for a series of 3-arylisoquinolines.


Anti-immunology: evasion of the host immune system by bacterial and viral pathogens.
Multicellular organisms possess very sophisticated defense mechanisms that are designed to effectively counter the continual microbial insult of the environment within the vertebrate host. However, successful microbial pathogens have in turn evolved complex and efficient methods to overcome innate and adaptive immune mechanisms, which can result in disease or chronic infections. Although the various virulence strategies used by viral and bacterial pathogens are numerous, there are several general mechanisms that are used to subvert and exploit immune systems that are shared between these diverse microbial pathogens. The success of each pathogen is directly dependant on its ability to mount an effective anti-immune response within the infected host, which can ultimately result in acute disease, chronic infection, or pathogen clearance. In this review, we highlight and compare some of the many molecular mechanisms that bacterial and viral pathogens use to evade host immune defenses.


Failing hospitals: mission statements to drive service improvement?
This paper aims to consider whether the hospital mission statement can be used as a management tool to improve service provision in failing hospitals. A literature search into the potential value and harm of hospital mission statements was done, followed by a survey of initial attitudes within a failing hospital. Do they indicate likely success of the tool? Mission statement is a potentially valuable leadership tool in the hospital environment. The success of its implementation is broadly dependent on its being developed with the support of stakeholders and its real application to all management decisions and questions of asset allocation. The potential danger lies in the fact that it can be seen as an expensive expression of politically correct platitudes which leads to cynical alienation of stakeholders. This was a small study within a single UK failing hospital, and extending its range will help to clarify whether its findings are typical of attitudes within such institutions. The likely success of the hospital mission statement as a management tool within a failing hospital is significantly limited by initial attitudes and preconceptions. Our research suggests that implementation is likely to be detrimental without preparatory involvement of the local community and hospital staff at all levels. Hospital management cannot be divorced from the local community where patient confidence must be maintained. This paper complements previous research, which has looked at mission statement acceptance among the upper echelons of hospital management.


A circadian variation of melphalan (L-phenylalanine nitrogen mustard) toxicity to murine bone marrow: relevance to cancer treatment protocols.
The toxicity of Melphalan to murine bone marrow was assessed by automated Coulter counts of femoral marrow nucleated cells. A significant dose-response slope (p less than 0.001) was shown and also a significant variation along the 24 h scale. With food available ad libitum and light from 06.00 to 18.00 hours, the minimum marrow depression occurred around 16.00 hours. Extrapolating these findings to human chemotherapy it would appear that prescription of the drug during the early part of the activity span (usually breakfast) will minimize marrow depression. This differs from a human study in which Melphalan was given at 'bedtime' as an adjuvant to mastectomy in breast carcinoma and in which there was leucopenia at some stage of treatment in all 103 patients. It is recommended that in future cancer therapy protocols test for circadian variability of white cell depression by varying treatment times systematically along the 24 h scale.


Efficacy of modified carbon molecular sieve with iron oxides or choline chloride-based deep eutectic solvent for the separation of CO2/CH4.
It is necessary to separate CO2 from biogas to improve its quality for the production of biomethane. Herein, an improvement in the separation of CO2/CH4via adsorption was achieved by modifying the surface of CMS. The surface modification of CMS was performed by impregnation with metal oxide (Fe3O4) and N-doping (DES-[ChCl:Gly]). Subsequently, the efficacy of the surface-modified CMS was investigated. This involved CMS modification, material characterization, and performance analysis. The uptake of CO2 by CMS-DES-[ChCl:Gly] and CMS-Fe3O4 was comparable; however, their performance for the separation of CO2/CH4 was different. Consequently, CMS-DES-[ChCl:Gly] and CMS-Fe3O4 exhibited ca. 1.6 times enhanced CO2 uptake capacity and ca. 1.70 times and 1.55 times enhanced CO2/CH4 separation, respectively. Also, both materials exhibited similar repeatability. However, CMS-DES-[ChCl:Gly] was more difficult to regenerate than CMS-Fe3O4, which is due to the higher adsorption heat value of the former (59.5 kJ).


The Influence of Personalised Sarcoma Care (PERSARC) Prediction Modelling on Clinical Decision Making in a Multidisciplinary Setting.
With soft-tissue sarcoma of the extremity (ESTS) representing a heterogenous group of tumors, management decisions are often made in multidisciplinary team (MDT) meetings. To optimize outcome, nomograms are more commonly used to guide individualized treatment decision making. To evaluate the influence of Personalised Sarcoma Care (PERSARC) on treatment decisions for patients with high-grade ESTS and the ability of the MDT to accurately predict overall survival (OS) and local recurrence (LR) rates. Two consecutive meetings were organised. During the first meeting, 36 cases were presented to the MDT. OS and LR rates without the use of PERSARC were estimated by consensus and preferred treatment was recorded for each case. During the second meeting, OS/LR rates calculated with PERSARC were presented to the MDT. Differences between estimated OS/LR rates and PERSARC OS/LR rates were calculated. Variations in preferred treatment protocols were noted. The MDT underestimated OS when compared to PERSARC in 48.4% of cases. LR rates were overestimated in 41.9% of cases. With the use of PERSARC, the proposed treatment changed for 24 cases. PERSARC aids the MDT to optimize individualized predicted OS and LR rates, hereby guiding patient-centered care and shared decision making.


The role of bisphosphonates in the prevention and treatment of osteoporosis.
Bisphosphonates are synthetic compounds that are taken up preferentially by the skeleton and suppress osteoclast-mediated bone resorption. There are structural differences among the various bisphosphonates that account for considerable differences in antiresorptive potencies and in activity/toxicity ratios. Bisphosphonates are given to patients with established vertebral osteoporosis, either intermittently or continuously, but controlled, long-term data are only available for intermittent regimens. They decrease the rate of bone loss, increase spinal bone mineral density (BMD), and stabilize BMD for at least 4 years of treatment without any significant side effects. This increase in bone mass is not due to redistribution of calcium in the skeleton, as at sites with predominantly cortical bone, BMD values either do not change or increase with treatment. Bisphosphonates also appear to decrease the frequency of new vertebral fractures in some patients with established osteoporosis, but this effect needs to be verified. Other issues that need to be addressed include the optimal mode and dose of administration and hence the choice of bisphosphonate, the duration of treatment, the changes in bone metabolism following treatment arrest, and finally the efficacy of bisphosphonates in the prevention of hip fractures.


What is the mid-wall linear high intensity "lesion" on cardiovascular magnetic resonance late gadolinium enhancement?
Cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) is a valuable technique for detecting myocardial disorders and fibrosis. However, we sometimes observe a linear, mid-wall high intensity signal in the basal septum in the short axis view, which often presents diagnostic difficulties in the clinical setting. The purpose of this study was to compare the linear, mid-wall high intensity in the basal septum identified by LGE with the anterior septal perforator arteries identified by coronary computed tomography angiography (CorCTA). We retrospectively selected 148 patients who underwent both CorCTA and CMR LGE within 1 year. In the interpretation of LGE, we defined a positive linear high intensity (LHI+) as follows: ① LHI in the basal septum and ② observable for 1.5 cm or more. All other patients were defined as a negative LHI (LHI-). In LHI+ patients, we assessed the correlation between the LHI length and the septal perforator artery length on CorCTA. We also compared the length of the septal perforator artery on CorCTA between LHI+ patients and LHI- patients. A population of 111 patients were used for further analysis. Among these , there were 55 LHI+ patients and 56 LHI- patients. In LHI+ patients, linear regression analysis revealed that there was a good agreement between LGE LHI and septal perforator arteries by CorCTA in terms of length measurements. The measured length of the anterior septal perforator arteries was significantly shorter in LHI- patients than in LHI+ patients (10 ± 8 mm vs. 21 ± 8 mm; P < 0.05). The LHI observed in the basal septum on short axis LGE may reflect contrast enhancement of the anterior septal perforator arteries. It is important to interpret this septal LHI against knowledge of anatomic structure, to avoid misinterpretations of LGE and prevent misdiagnosis.


Muscle-specific acute changes in passive stiffness of human triceps surae after stretching.
It remains unclear whether the acute effect of stretching on passive muscle stiffness differs among the synergists. We examined the muscle stiffness responses of the medial (MG) and lateral gastrocnemii (LG), and soleus (Sol) during passive dorsiflexion before and after a static stretching by using ultrasound shear wave elastography. Before and after a 5-min static stretching by passive dorsiflexion, shear modulus of the triceps surae and the Achilles tendon (AT) during passive dorsiflexion in the knee extended position were measured in 12 healthy subjects. Before the static stretching, shear modulus was the greatest in MG and smallest in Sol. The stretching induced significant reductions in shear modulus of MG, but not in shear modulus of LG and Sol. The slack angle was observed at more plantar flexed position in the following order: AT, MG, LG, and Sol. After the stretching, the slack angles of each muscle and AT were significantly shifted to more dorsiflexed positions with a similar extent. When considering the shift in slack angle, the change in MG shear modulus became smaller. The present study indicates that passive muscle stiffness differs among the triceps surae, and that the acute effect of a static stretching is observed only in the stiff muscle. However, a large part of the reduction of passive muscle stiffness at a given joint angle could be due to an increase in the slack length.


[Improvement of sonographic visualization of cannula needle tips by alignment of the needle lumen : In vitro investigation of established needle tip forms].
In the context of ultrasound-guided peripheral nerve blocks (regional anesthesia), clear visualization of the needle tip and the target structure are mandatory for the performance of a safe puncture and injection. The purpose of this in vitro study was to analyze the visualization of different forms of needle tips and calibers of cannulas in a phantom simulating human tissue, with the help of a standardized image analysis system. Different depths and angles of the puncture needle in relation to the ultrasound probe were tested. Cannula needles established for use in regional anesthesia with different surfaces, diameters and needle tip form in 23 different combinations were analyzed. A gelatine-based phantom was used to simulate human tissue. The standardized visualization of the needle tip with the ultrasound probe was performed in plane at different angles (30°, 45° and 60°), depths of penetration (1 cm, 2 cm and 3 cm) and two different alignments of the cannula needle lumen to the ultrasound probe (0° and 180°). The screenshots of the ultrasound pictures were analyzed by quantifying the pixel brightness around the needle tip (region of interest) with a standardized software (score 0-255). In this study 1104 ultrasound images of cannula needles were analyzed. Diminished scores (reduced pixel brightness) of the needle tips were documented with increasing distance from the ultrasound probe. Comparison of punctures at angles of 30° and 45° showed no differences in needle tip visibility (same scores) but punctures at an angle of 60° were poorly visualized compared with 30° and 45° (mean scores 87.90 ± 11.60 vs. 78.40 ± 12.07, p < 0.001 and 81.85 ± 11.79 vs. 78.40 ± 12.07, p < 0.001, respectively). The direct alignment of the cannula lumen towards the ultrasound probe (0°) was significantly more easily visualized when compared with the reverse alignment of 180° (mean scores 86.90 ± 12.74 vs. 84.80 ± 11.66, p = 0.003, respectively). No differences in visibility were detected between the different cannula needle diameters examined. The Sprotte cannula showed the best visibility score with respect to the cut of the needle tip (mean score 89.40 ± 11.72). The visibility of cannulas in ultrasound scans depends on the ultrasound frequency, angle of the puncture in relation to the ultrasound probe and the depth of penetration. The results of this study showed that direct alignment of the cannula needle lumen towards the ultrasound probe (0°) independently improved needle tip visualization. This simple measure allows a significant improvement in the safe performance of ultrasound-guided peripheral nerve blocks.


Degree of light damage to the retina varies with time of day of bright light exposure.
After adaptation to cyclic illumination (14:10 light-dark cycle; intensity = 1.4 log ftc) male albino rats were exposed to brighter light (2.15 log ftc) seven hours daily for 25 days. The extent of retinal damage was determined histologically. Daily exposure to bright light in the morning produced greater photoreceptor loss than daily afternoon exposure. Severe retinal damage was partially prevented by brief light adaptation (20 minutes duration, at 1.4 log ftc intensity) before the onset of morning exposure. However, light adaptation did not remove the differential effect of time of day. The authors conclude that increased light exposure during the period of rod outer segment phagocytosis enhances photoreceptor damage.


Synthetic selenium nanoparticles as co-adjuvant improved immune responses against methicillin-resistant Staphylococcus aureus.
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of hospital-acquired infections worldwide, which is resistant to many antibiotics, resulting in significant mortality in societies. Vaccination is a well-known approach to preventing disease. Autolysin, a surface-associated protein in S. aureus with multiple functions, is a suitable candidate for vaccine development. As a co-adjuvant, selenium nanoparticles (SeNPs) can increase the immune system, presumably resulting in increased vaccine efficacy. The present study evaluated the immunogenicity and defense of recombinant autolysin formulated in SeNPs and Alum adjuvants against MRSA. r-Autolysin was expressed and purified by the Ni-NTA affinity chromatography. SeNPs were synthetically obtained from sodium dioxide, followed by an assessment of shape and size using SEM and DLS. Balb/c mice were injected subcutaneously with 20 mg of r-autolysin formulated in Alum and SeNps adjuvants three times with the proper control group in 2 weeks intervals. Cytokine profile and isotyping ELISA were conducted to determine the type of induced immunity. Opsonophagocytosis tests assessed the functional activity of the vaccine, and the bacterial burden from the infected tissues was determined. Results showed that mice receiving SeNps and r-Autolysin had higher levels of total IgG and isotypes (IgG1 and IgG2a) and increased cytokine levels (IFN-γ, TNF-α, IL-12, and IL-4) as compared with those only receiving autolysin and PBS as a control. More importantly, mice immunized with SeNps and r-Autolysin exhibited a decrease in mortality and bacterial burden compared to the control group. We concluded that SeNps could stimulate immune responses and can be used as an adjuvant element in vaccine formulation.


MR Fingerprinting-A Radiogenomic Marker for Diffuse Gliomas.
(1) Background: Advanced MR imaging (MRI) of brain tumors is mainly based on qualitative contrast images. MR Fingerprinting (MRF) offers a novel approach. The purpose of this study was to use MRF-derived T1 and T2 relaxation maps to differentiate diffuse gliomas according to isocitrate dehydrogenase (IDH) mutation. (2) Methods: Twenty-four patients with histologically verified diffuse gliomas (14 IDH-mutant, four 1p/19q-codeleted, 10 IDH-wildtype) were enrolled. MRF T1 and T2 relaxation times were compared to apparent diffusion coefficient (ADC), relative cerebral blood volume (rCBV) within solid tumor, peritumoral edema, and normal-appearing white matter (NAWM), using contrast-enhanced MRI, diffusion-, perfusion-, and susceptibility-weighted imaging. For perfusion imaging, a T2* weighted perfusion sequence with leakage correction was used. Correlations of MRF T1 and T2 times with two established conventional sequences for T1 and T2 mapping were assessed (a fast double inversion recovery-based MR sequence ('MP2RAGE') for T1 quantification and a multi-contrast spin echo-based sequence for T2 quantification). (3) Results: MRF T1 and T2 relaxation times were significantly higher in the IDH-mutant than in IDH-wildtype gliomas within the solid part of the tumor (p = 0.024 for MRF T1, p = 0.041 for MRF T2). MRF T1 and T2 relaxation times were significantly higher in the IDH-wildtype than in IDH-mutant gliomas within peritumoral edema less than or equal to 1cm adjacent to the tumor (p = 0.038 for MRF T1 mean, p = 0.010 for MRF T2 mean). In the solid part of the tumor, there was a high correlation between MRF and conventionally measured T1 and T2 values (r = 0.913, p < 0.001 for T1, r = 0.775, p < 0.001 for T2), as well as between MRF and ADC values (r = 0.813, p < 0.001 for T2, r = 0.697, p < 0.001 for T1). The correlation was weak between the MRF and rCBV values (r = -0.374, p = 0.005 for T2, r = -0.181, p = 0.181 for T1). (4) Conclusions: MRF enables fast, single-sequence based, multi-parametric, quantitative tissue characterization of diffuse gliomas and may have the potential to differentiate IDH-mutant from IDH-wildtype gliomas.


A probabilistic model of biological ageing of the lungs for analysing the effects of smoking, asthma and COPD.
Although a large body of literature is available that describes the effects of smoking, asthma and COPD on lung function, most studies are restricted to a small age range and to one factor. As a consequence, available results are incomplete and often difficult to compare, also due to the ways the effects are expressed. Furthermore, current approaches consider one type of measurement only or several types separately. We propose a probabilistic model that expresses the effects as number of years added to chronological age or, in other words, that estimates the biological age of the lungs. Using biological age as a measure of the effects has the advantage of facilitating the understanding of their severity and comparison of results. In our model, chronological age and other factors affecting the health status of the lungs generate biological age, which in turn generates lung function measurements. This structure enables the use of multiple types of measurement to obtain a more precise estimate of the effects and parameter sharing for characterization over large age ranges and of co-occurrence of factors with little data. We treat the parameters that model smoking habits and lung diseases as random variables to obtain uncertainty in the estimated effects. We use the model to investigate the effects of smoking, asthma and COPD on the TwinsUK Registry. Our results suggest that the combination of smoking with lung disease(s) has higher effect than smoking or lung disease(s) alone, and that in smokers, co-occurrence of asthma and COPD is more detrimental than asthma or COPD alone. The proposed model or other models based on a similar approach could be of help in improving the understanding of factors affecting lung function by enabling characterizations over large age ranges and of co-occurrence of factors with little data and the use of multiple types of measurement. The software implementing the model can be downloaded at the first author's webpage.


The major B and T cell determinant on pigeon cytochrome c in B10.a mice.
The specificities of B10.A B and T cells responding to pigeon cytochrome c have been examined. Proliferating T cells recognize glutamine 100 and lysine 104 and can be stimulated in vitro by either native cytochrome c molecules or certain of their CNBr-cleavage fragments. In contrast only molecules with the native cytochrome c conformation were found to interact with B10.A antipigeon cytochrome c antibodies. Antibodies appear to recognize a determinant or determinants which overlaps with that which elicits the T cell proliferative response.


Self assembly of human septin 2 into amyloid filaments.
Septins are a conserved group of GTP-binding proteins that form hetero-oligomeric complexes which assemble into filaments. These are essential for septin function, including their role in cytokinesis, cell division, exocytosis and membrane trafficking. Septin 2 (SEPT2) is a member of the septin family and has been associated with neurofibrillary tangles and other pathological features of senile plaques in Alzheimer's disease. An in silico analysis of the amino acid sequence of SEPT2 identified regions with a significant tendency to aggregate and/or form amyloid. These were all observed within the GTP-binding domain. This was consistent with the experimental identification of a structure rich in β-sheet during temperature induced unfolding transitions observed for both the full length protein and the GTP-binding domain alone. This intermediate state is characterized by irreversible aggregation and has the ability to bind Thioflavin-T, suggesting its amyloid nature. Under electron microscopy, fibers extending for several micrometers in length could be visualized. The results shown in this study support the hypothesis that single septins, when present in excess or with unbalanced stoichiometries, may be unstable and assemble into amyloid-like structures.