Structure and chemical state of the Pt(557) surface during hydrogen oxidation reaction studied by in situ scanning tunneling microscopy and X-ray photoelectron spectroscopy.
The surface structure of Pt(557) during the catalytic oxidation of hydrogen was studied with in situ scanning tunneling microscopy and X-ray photoelectron spectroscopy. At 298 K, the surface Pt oxide formed after exposing Pt(557) to approximately 1 Torr of O2 can be readily removed by H2, at H2 partial pressures below 50 mTorr. Water is detected as the product in the gas phase, which also coadsorbs with hydroxyl groups on the Pt(557) surface.


Hybrid life cycle assessment comparison of colloidal silica and cement grouted soil barrier remediation technologies.
Site remediation involves balancing numerous costs and benefits but often neglects the environmental impacts over the entire project life cycle. Life cycle assessment (LCA) offers a framework for inclusion of global environmental "systems-level" decision metrics in combination with technological and cost analysis. We compare colloidal silica (CS) and cement grouted soil barrier remediation technologies for soils affected by low level radionuclides at a U.S. Superfund site using hybrid LCA methods. CS is a new, high performance grouting material installed using permeation grouting techniques. Cement, a more traditional grouting material, is typically installed using jet grouting techniques. Life cycle impacts were evaluated using the US EPA TRACI 2 model. Results show the highest life cycle environmental impacts for the CS barrier occur during materials production and transportation to the site. In general, the life cycle impacts for the cement barrier were dominated by materials production; however, in the extreme scenario the life cycle impacts were dominated by truck transportation of spoils to a distant, off-site radioactive waste facility. It is only in the extreme scenario tested in which soils are transported by truck (Option 2) that spoils waste transport dominates LCIA results. Life cycle environmental impacts for both grout barriers were most sensitive to resource input requirements for manufacturing volumes and transportation. Uncertainty associated with the efficacy of new technology such as CS over its required design life indicates that barrier replacement could increase its life cycle environmental impact above that of the cement barrier.


Erythroid and granulocytic colony growth in cultures supplemented with human serum lipoproteins.
The ability of human serum to support erythroid and granulocytic colony formation has been investigated. It was found that normal human serum could replace fetal calf serum in the cultures and was able to support the growth of these hemopoietic colonies. Serum fractions enriched for low density lipoproteins, either by precipitation with Heparin-Mn++ or by ultracentrifugation, was found to contain this growth supporting activity of human serum.


Brain myelin water fraction is associated with APOE4 allele status in patients with cognitive impairment.
Apolipoprotein E4 (APOE4) is a major genetic risk factor for Alzheimer's disease. However, the effect of APOE4 status on myelin remains unclear. This study investigated the effect of APOE4 on myelin content in cognitively impaired individuals using T2* gradient echo (GRE)-based myelin water fraction (MWF) imaging. Between August 2017 and January 2019, we evaluated 39 cognitively impaired patients (median age, 75 years; male:female = 8:31; Alzheimer's disease: mild cognitive impairment = 11:28). We obtained brain MWF values from white matter hyperintensities (WMHs) and normal-appearing white matter (NAWM). Linear regression analysis was performed to investigate the relationship between the APOE4 status and MWF and cognitive function and MWF. Among the 39 cognitively impaired patients, nine (23.1%) were APOE4 carriers and 30 (76.9%) were noncarriers. APOE4 carriers had a lower hippocampal volume than noncarriers (p = .045), but other brain volume parameters were not differed. After age adjustment, the APOE4 status was significantly associated with reduced MWF in NAWM (β = -0.310 per allele; p = .049) but not in WMH (β = -0.258 per allele; p = .113). After age adjustment, MWF in NAWM was significantly associated with Mini-Mental State Examination score (β = 0.313, p = .031). T2* GRE-based MWF imaging can reveal myelin loss, particularly in NAWM, in cognitively impaired patients among APOE4 carriers. In vivo MWF in NAWM might be a novel imaging marker of Alzheimer's disease, for clarifying the interactions between the white matter and cognitive dysfunction with respect to the APOE4 status.


The chirality origin of retinal-carotenoid complex in gloeobacter rhodopsin: a temperature-dependent excitonic coupling.
Retinal proteins play significant roles in light-induced protons/ions transport across the cell membrane. A recent studied retinal protein, gloeobacter rhodopsin (gR), functions as a proton pump, and binds the carotenoid salinixanthin (sal) in addition to the retinal chromophore. We have studied the interactions between the two chromophores as reflected in the circular dichroism (CD) spectrum of gR complex. gR exhibits a weak CD spectrum but following binding of sal, it exhibits a significant enhancement of the CD bands. To examine the CD origin, we have substituted the retinal chromophore of gR by synthetic retinal analogues, and have concluded that the CD bands originated from excitonic interaction between sal and the retinal chromophore as well as the sal chirality induced by binding to the protein. Temperature increase significantly affected the CD spectra, due to vanishing of excitonic coupling. A similar phenomenon of excitonic interaction lose between chromophores was recently reported for a photosynthetic pigment-protein complex (Nature Commmun, 9, 2018, 99). We propose that the excitonic interaction in gR is weaker due to protein conformational alterations. The excitonic interaction is further diminished following reduction of the retinal protonated Schiff base double bond. Furthermore, the intact structure of the retinal ring is necessary for obtaining the excitonic interaction.


Gum Arabic polysaccharide embedded L-cysteine capped copper oxide nanocarriers selectively inhibit fluconazole-resistant C. albicans biofilm and remove the toxic dye from wastewater.
Copper oxide nanocarriers have attracted increasing interest in the scientific community, including antimicrobial applications. Candida biofilm developed causes serious clinical problems, leading to drug failure caused by its inherent drug tolerance. Nanocarriers are a good alternative approach to solving this challenge because of their excellent penetration power inside biofilms. Hence, main objectives of this research were to prepare gum arabic-embedded L-cysteine-capped copper oxide nanocarriers (GCCuO NCs) and tested against C. albicans and explore another application. To achieve the main research objectives, GCCuO NCs were synthesized and investigated for antibiofilm potency against C. albicans. Various methods were employed to measure antibiofilm potency such as biofilm assay etc., of NCs. The nano size of GCCuO NCs is advantageous for augmenting penetration power and retention into biofilms. GCCuO NCs at 100 μg/mL exhibited significant antibiofilm activity against the C. albicans DAY185 by switching of yeast-to-hyphae and gene perturbation. The level of CR dye adsorption was 58.96 % using 30 μg/mL of NCs. Based on effective C. albicans biofilm inhibition and CR dye adsorption capacity of NCs, it can be suggested that present research work opens an innovative path to treat biofilm-associated fungal infections, and these NCs can be used for environmental remedies.


Comparison of genomic selection models for exploring predictive ability of complex traits in breeding programs.
Traits with a complex unknown genetic architecture are common in breeding programs. However, they pose a challenge for selection due to a combination of complex environmental and pleiotropic effects that impede the ability to create mapping populations to characterize the trait's genetic basis. One such trait, seedling emergence of wheat (Triticum aestivum L.) from deep planting, presents a unique opportunity to explore the best method to use and implement genetic selection (GS) models to predict a complex trait. Seventeen GS models were compared using two training populations, consisting of 473 genotypes from a diverse association mapping panel phenotyped from 2015 to 2019 and the other training population consisting of 643 breeding lines phenotyped in 2015 and 2020 in Lind, WA, with 40,368 markers. There were only a few significant differences between GS models, with support vector machines reaching the highest accuracy of 0.56 in a single breeding line trial using cross-validations. However, the consistent moderate accuracy of the parametric models indicates little advantage of using nonparametric models within individual years, but the nonparametric models show a slight increase in accuracy when combing years for complex traits. There was an increase in accuracy using cross-validations from 0.40 to 0.41 using diversity panels lines to breeding lines. Overall, our study showed that breeders can accurately predict and implement GS for a complex trait by using nonparametric machine learning models within their own breeding programs with increased accuracy as they combine training populations over the years.


[Combined approach for the treatment of spontaneous temporal encephaloceles: transmastoid plus temporal minicraniotomy].
Spontaneous encephaloceles are defined as brain herniations with no apparent cause. The aim of this paper is to describe the surgical technique performed in our department. We reviewed the last 3 cases treated with combined approach (transmastoid plus minicraniotomy) with 2-layer closure. In all cases the bone defects were located and successfully sealed. We had no postoperative complications. There were no relapses in our follow-up period. The transmastoid approach has the advantage over the open approach with middle fossa craniotomy in that it locates the bone defect with no brain retraction. Nevertheless, it is not useful in large-sized, multiple or anterior defects. Due to those drawbacks, we think that the combined approach with temporal minicraniotomy is the best choice for this entity.


LazySampling and LinearSampling: fast stochastic sampling of RNA secondary structure with applications to SARS-CoV-2.
Many RNAs fold into multiple structures at equilibrium, and there is a need to sample these structures according to their probabilities in the ensemble. The conventional sampling algorithm suffers from two limitations: (i) the sampling phase is slow due to many repeated calculations; and (ii) the end-to-end runtime scales cubically with the sequence length. These issues make it difficult to be applied to long RNAs, such as the full genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To address these problems, we devise a new sampling algorithm, LazySampling, which eliminates redundant work via on-demand caching. Based on LazySampling, we further derive LinearSampling, an end-to-end linear time sampling algorithm. Benchmarking on nine diverse RNA families, the sampled structures from LinearSampling correlate better with the well-established secondary structures than Vienna RNAsubopt and RNAplfold. More importantly, LinearSampling is orders of magnitude faster than standard tools, being 428× faster (72 s versus 8.6 h) than RNAsubopt on the full genome of SARS-CoV-2 (29 903 nt). The resulting sample landscape correlates well with the experimentally guided secondary structure models, and is closer to the alternative conformations revealed by experimentally driven analysis. Finally, LinearSampling finds 23 regions of 15 nt with high accessibilities in the SARS-CoV-2 genome, which are potential targets for COVID-19 diagnostics and therapeutics.


Study of biological safety of scaffold material with heterologous deproteinized bone.
To evaluate the biological safety of manufactured heterologous deproteinized bone and to provide an experimental basis for clinical applications. Deproteinized bone (10 mm) and leaching liquor were made from pig ribs with a series of physical and chemical methods, then were evaluated through acute and subacute toxicity test, hemolysis test, pyrogen test, intracutaneous test, intramuscular implantation test and cytotoxity test. No obvious toxicity, hemolysis, pyrogenic characteristics, skin irritation, inflammatory reaction after intramuscular implantation and cytotoxity were observed. The heterologous deproteinized bone has good biological safety and meets all the demands of scaffold material for tissue engineering.


Growth and mortality in mountain hares: the effect of sex and date of birth.
Current theory suggests that high juvenile growth effort, may result in higher mortality. This prediction is tested in mountain hares (Lepus timidus), by examination of post-weaning growth and mortality of males and females. Dates of birth were estimated from weight at first capture and growth in body weight and hind foot length was described by the logistic growth equation. Although adult female hares are on average larger than males, this results from a longer period of growth and not from a faster growth rate. There was no clear sex bias in mortality, a slight but not significantly greater proportion of males suffered mortality during the growth period. Predictions as to sex difference in mortality should specify which aspects of growth (rate or duration) are the agents of mortality, since the two parameters are not necessarily positively associated. Overall asymptotic body size decreased and rate of growth increased from early through to late-born young. Rate of growth in hind foot length was greater in late-born males but not in late-born females as compared with those born earlier. It is hypothesized that late-born males are more tightly constrained to complete growth and subsequent sexual maturation earlier than late-born females.


Comparative experimental study of myocardial energy metabolism during ventricular workload induced by chronic stenoses of ascendent aorta and pulmonary artery.
In this paper, an attempt was made to describe the alterations of the myocardial energy metabolism following moderate stenoses of aorta or pulmonary artery. Biochemical investigations regarding the main high energy phosphates and a large series of dehydrogenases in the myocardium of the overloaded ventricles have revealed the following facts: (1) the myocardial CP-CPK system appears to be more labile than the myocardial AMP-ATP system in response to a ventricular overload; (2) the changes in the amounts of myocardial high energy phosphates seem to be more important in the right chronic cardiac overload than in the left one; (3) before the overloaded ventricle becomes insufficient, the myocardial dehydrogenase system elicits no alteration, suggesting that the oxidative phosphorylation is not affected; (4) there is a closer relationship between the coronary flow and pressure and the myocardial energy metabolism than that existing between this metabolism and the tension of the myocardial fibres following a persistent increase in the systemic arterial resistance.


Evidence vs experience in the surgical management of necrotizing enterocolitis and focal intestinal perforation.
Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are neonatal intestinal emergencies that affect premature infants. Although most cases of early NEC can be successfully managed with medical therapy, prompt surgical intervention is often required for advanced or perforated NEC and FIP. The surgical management and treatment of FIP and NEC are discussed on the basis of literature review and our personal experience. Surgical options are diverse, and include peritoneal drainage, laparotomy with diverting ostomy alone, laparotomy with intestinal resection and primary anastomosis or stoma creation, with or without second-look procedures. The optimal surgical therapy for FIP and NEC begins with prompt diagnosis and adequate fluid resuscitation. It appears that there is no significant difference in patient outcome based on surgical management alone. However, the infant's weight, comorbidities, surgeon preference and timing of intervention should be taken into account before operative intervention.


Magnetic resonance imaging system for intraoperative margin assessment for DCIS and invasive breast cancer using the ClearSight™ system in breast-conserving surgery-Results from a postmarketing study.
Breast-conserving surgery (BCS) is followed by reoperations in approximately 25%. Reoperations lead to an increased risk of infection and wound healing problems as well as a worse cosmetic outcome. Several technical approaches for an intraoperative margin assessment to decrease the reoperation rate are under evaluation, some of them are still experimental. A prospective single-arm post-marketing study with 60 patients undergoing BCS for ductal carcinoma in situ (DCIS) and invasive breast cancer was conducted. The specimen was intraoperatively examined by the ClearSight™ system, a mobile magnetic resonance imaging system that is based on a diffusion-weighted imaging protocol. However, the results were blinded to the surgeon. The ClearSight™ system was performed for both ductal and lobular breast cancer and DCIS, with a sensitivity of 0.80 (95% confidence interval [CI]: 0.44-0.96) and a specificity of 0.84 (95% CI 0.72-0.92), with an overall diagnostic accuracy of 80%. Had the ClearSight™ been known to the surgeon intraoperatively, the reoperation rate would have been reduced by 83% for invasive carcinoma, from 10% to 2%, and 50% for DCIS, from 30% to 15% reoperations. A trial designed to examine the impact on reoperation rates is currently ongoing.


NABTT 0502: a phase II and pharmacokinetic study of erlotinib and sorafenib for patients with progressive or recurrent glioblastoma multiforme.
The signal transduction pathways of epidermal growth factor receptor and Ras are both important in the growth of glioblastoma multiforme (GBM). We hypothesized that inhibition of both pathways would improve the survival time of patients with recurrent GBM. Patients with recurrent/progressive GBM with 0-2 prior chemotherapy regimens received erlotinib 150 mg once daily and sorafenib 400 mg twice daily until progression. The primary endpoint was overall survival. Pharmacokinetic sampling was performed during cycle 1. The median overall survival was 5.7 months. Progression-free survival at 6 months was 14%. Toxicity was manageable. Clearance of erlotinib was markedly enhanced by sorafenib. The study did not meet its objective of a 30% increase in overall survival time compared with historical controls. Erlotinib and sorafenib have significant pharmacokinetic interactions that may negatively impact the efficacy of the combination regimen.


A third species of the rarely collected Oriental hoverfly genus Furcantenna Cheng, 2008 (Diptera, Syrphidae, Microdontinae).
Furcantenna malayana sp. nov. is described from Peninsular Malaysia, based on a single female collected in 1962. The other two known species of this genus are also known from single specimens, from Southeastern China and Nepal. A key to the species is given, and the taxonomy and distribution of the genus are discussed.


Analysis of anterior and posterior corneal curvature changes using Orbscan technology in radial keratotomy eyes exposed to hypoxia.
To study the changes in anterior and posterior corneal curvatures in radial keratotomy (RK) and normal eyes exposed to hypoxia using Orbscan (Bausch & Lomb) technology. Department of Ophthalmology, Madigan Army Medical Center, Tacoma, Washington, USA. At sea level, 11 RK subjects and 10 control subjects were exposed to ocular surface hypoxia in 1 eye by filtering humidified, compressed 100% nitrogen (0% oxygen) through an airtight goggle system for 2 hours. The contralateral eye was exposed to humidified, compressed air (21% oxygen) simultaneously through the airtight goggle system. Orbscan analysis was performed in each subject before and immediately after gas exposure. This analysis included measurement of the anterior axial and posterior axial corneal curvatures as well as corneal pachymetry. In the RK eyes exposed to 100% nitrogen gas, there was a statistically significant flattening in the anterior axial corneal curvature (P = .0012) and in the posterior axial corneal curvature (P = .0067). Radial keratotomy and control eyes exposed to air and control eyes exposed to 100% nitrogen gas demonstrated no statistically significant change in the anterior axial or posterior axial corneal curvature. Corneal hypoxia induced a statistically significant flattening in the anterior axial and posterior axial corneal curvatures in eyes that had had RK. There was no significant change in these curvatures in RK eyes exposed to air and in control eyes exposed to air or 100% nitrogen gas.


Long COVID-19 in children: an Italian cohort study.
Long COVID-19 syndrome is a complex of symptoms that occurs after the acute SARS-CoV-2 infection, in the absence of other possible diagnoses. Studies on Long COVID-19 in pediatric population are scanty and heterogeneous in design, inclusion criteria, outcomes, and follow-up time. The objective of the present study is to assess the prevalence of Long COVID-19 syndrome in a cohort of Italian pediatric primary care patients, observed for a period of time of 8 to 36 weeks from healing. Prevalence was also assessed in a cohort of pediatric patients hospitalized during acute infection. Data concerning 629 primary care patients with previous acute SARS-CoV-2 infection were collected by a questionnaire filled in by Primary Care Pediatrician (PCP). The questionnaire was administrated to patients by 18 PCPs based in 8 different Italian regions from June to August 2021. Data concerning 60 hospitalized patients were also collected by consultation of clinical documents. Cumulative incidence of Long COVID-19 resulted to be 24.3% in primary care patients and 58% in hospitalized patients. The most frequently reported symptoms were abnormal fatigue (7%), neurological (6.8%), and respiratory disorders (6%) for the primary care cohort. Hospitalized patients displayed more frequently psychological symptoms (36.7%), cardiac involvement (23.3%), and respiratory disorders (18.3%). No difference was observed in cumulative incidence in males and females in both cohorts. Previous diseases did not influence the probability to develop Long COVID-19. The prevalence of Long COVID-19 was 46.5% in children who were symptomatic during acute infection and 11.5% in asymptomatic ones. Children aged 0 to 5 years had a greater risk to develop respiratory symptoms, while adolescents (aged 11-16 years) had a greater risk to develop neurological and psychological Long COVID-19 symptoms. Our study demonstrates that Long COVID-19 is a reality in pediatric age and could involve even patients with mild or no acute symptoms. The results stress the importance of monitoring primary care pediatric patients after acute COVID-19 infection and the relevance of vaccination programs in pediatric population, also in order to avoid the consequences of Long COVID-19 syndrome.


Quantifying anthropogenic threats affecting Marine Protected Areas in developing countries.
Conservation's capacity to deal with anthropogenic environmental threats within Marine Protected Areas (MPAs) varies enormously, especially in developing countries that are often immersed in weak enforcement, ineffective management and shortages of resources. A deeper understanding of the causes of these threats is fundamental for identifying effective management solutions. Here, we investigate the presumptive drivers of environmental threats across 40 Brazilian MPAs. We categorized and quantified environmental threats from two independent sources: i) the results of systematic social surveys carried out as part of WWF's RAPPAM assessment, as primary data source, and; ii) data gathered from news media articles related to the MPAs (secondary data source). We identified 461 reports of threats that we classified into three general categories: overexploitation, urbanization and land use threats. The presence of overexploitation threats was strongly associated with extreme poverty of local communities close to the MPAs. Threats also seem to be more frequent in category V MPAs, which in Brazil are Environmental Protection Areas (EPA), with multiple use objectives. Threats were concentrated on the North and Southeast coasts of Brazil. We found that data from news media can be used for qualitative assessment of threats, but has limited potential for quantification. Our findings highlight the need for policy makers and MPA managers to adopt a broader perspective that considers the role of social inequalities in promoting and exacerbating environmental threats. While recognizing that conservation has limited capacity to address the widespread social inequalities found in many tropical developing countries, if the socioeconomic context of local communities is significantly compromising conservation efforts it may be necessary to target and prioritize social interventions as a prerequisite for effective MPA management and governance.


Proopiomelanocortin interference in the measurement of adrenocorticotrophic hormone: a United Kingdom National External Quality Assessment Service study.
It is recognized that measurement of ACTH-precursor peptides including proopiomelanocortin (POMC) has clinical utility in identifying the aetiology of Cushing's syndrome. Recent data have also demonstrated cross-reactivity of POMC in ACTH immunoassays used in clinical laboratories. The aim of this study was to assess the cross-reactivity of POMC in the main commercial immunoassays for ACTH and to survey the awareness of laboratory professionals to this potential interference. To assess cross-reactivity, specimens containing ACTH and/or POMC were prepared by the UK National External Quality Assessment Service (UK NEQAS) [Edinburgh]. A separate interpretative exercise was also sent to participating laboratories. Eighty-seven laboratories measured 'total' ACTH (i.e. ACTH and/or POMC) in their assays. Cross-reactivity of POMC varied from a mean of 1·6-4·7% (reflected in a large percentage increase in measured ACTH of up to 261% due to POMC cross-reactivity) depending on the manufacturer. Major differences in the clinical interpretation of test results were observed in returned responses to the interpretative exercise. An appraisal of POMC cross-reactivity in currently available ACTH immunoassays has been achieved. Cross-reactivity was sufficient to detect ACTH precursors at concentrations that could be found in patients with ectopic ACTH syndrome. These data will assist laboratories in interpreting results when assessing the hypothalamic-pituitary-adrenal axis. Endocrinologists and laboratory professionals should be aware of the degree of cross-reactivity in ACTH immunoassay in order to minimize the risk of misinterpretation of results and/or potentially delayed treatment.


Production of the soluble human Fas ligand by Dictyostelium discoideum cultivated on a synthetic medium.
Human Fas ligand (hFasL) is of considerable interest since it is a type II transmembrane glycoprotein that induces programmed cell death, or apoptosis. In this study Dictyostelium discoideum was used to produce a soluble form of the human Fas ligand. The recombinant cells were adapted to a modified synthetic FM medium, called SIH medium. Cells adapted to the SIH medium reached about 2 times higher cell densities and hFasL concentrations on this medium compared with cells growing on the standard complex medium HL-5C. Even higher values were achieved by a dissolved oxygen-controlled fed-batch cultivation in a conventional stirred bioreactor on SIH medium. Cell densities of up to 5.5 x 10(7) ml(-1) and a maximum hFasL concentration of 148 microgl(-1) were obtained. These results were further improved by means of continuous cultivation of D. discoideum in a bioreactor equipped with cell retention by microfiltration. At low space velocity very high cell densities of up to 2.4 x 10(8) ml(-1) and hFasL concentrations of up to 205 microgl(-1) were achieved.


Congenital central hypoventilation syndrome with hyperinsulinism in a preterm infant.
Congenital central hypoventilation syndrome (CCHS), a rare disorder typically presenting in the newborn period, results in over 90% of cases from PHOX2B polyalanine repeat mutations. It is characterized by alveolar hypoventilation, symptoms of autonomic nervous system dysregulation, and in a subset of cases Hirschsprung's disease and, later, tumors of neural crest origin. We describe a preterm infant with severe phenotype of CCHS and hyperinsulinism. A novel de novo heterozygote missence mutation (Gly68Cys) in the PHOX2B gene could be identified. Based on the observation of three patients presenting with the combination of congenital hyperinsulinism and CCHS, hyperinsulinism might represent an additional clinical feature of CCHS.


41-month follow-up of risk factors correlated with new coronary events in 708 elderly patients.
A prospective study correlated coronary risk factors with new coronary events in 192 elderly men and 516 elderly women, mean age 82 +/- 8 years. Follow-up was 41 +/- 6 months (range 24-44). Coronary events (myocardial infarction, primary ventricular fibrillation, and sudden cardiac death) occurred in 64 of 192 men (33%) and in 149 of 516 women (29%), P not significant. Using univariate analysis, significant risk factors for coronary events were antecedent coronary artery disease, cigarette smoking, hypertension, diabetes mellitus, serum total cholesterol (TC) greater than or equal to 200 mg/dL and greater than or equal to 250 mg/dL, serum high-density lipoprotein cholesterol (HDL-C) less than 35 mg/dL, and serum TC/HDL-C greater than or equal to 6.5 in men and women, and obesity in women. Using multivariate analysis, significant risk factors for coronary events were age, antecedent coronary artery disease, cigarette smoking, hypertension, diabetes mellitus, and serum TC in men and women and serum HDL-C and serum triglycerides in women. Using univariate analysis, significant risk factors for coronary events in men and women with antecedent coronary artery disease were cigarette smoking, diabetes mellitus, serum TC greater than or equal to 250 mg/dL, and serum TC/HDL-C greater than or equal to 6.5. Using multivariate analysis, significant risk factors for coronary events in men and women with antecedent coronary artery disease were age, cigarette smoking, diabetes mellitus, serum TC, serum HDL-C, and serum triglycerides.(ABSTRACT TRUNCATED AT 250 WORDS)


Oxygen transfer rate identifies priming compounds in parsley cells.
In modern agriculture, the call for an alternative crop protection strategy increases because of the desired reduction of fungicide and pesticide use and the continuously evolving resistance of pathogens and pests to agrochemicals. The direct activation of the plant immune system does not provide a promising plant protection measure because of high fitness costs. However, upon treatment with certain natural or synthetic compounds, plant cells can promote to a fitness cost-saving, primed state of enhanced defense. In the primed state, plants respond to biotic and abiotic stress with faster and stronger activation of defense, and this is often associated with immunity and abiotic stress tolerance. Until now, the identification of chemical compounds with priming-inducing activity (so-called plant activators) relied on tedious and invasive approaches, or required the late detection of secreted furanocoumarin phytoalexins in parsley cell cultures. Thus, simple, fast, straightforward, and noninvasive techniques for identifying priming-inducing compounds for plant protection are very welcome. This report demonstrates that a respiration activity-monitoring system (RAMOS) can identify compounds with defense priming-inducing activity in parsley cell suspension in culture. RAMOS relies on the quasi-continuous, noninvasive online determination of the oxygen transfer rate (OTR). Treatment of parsley culture cells with the known plant activator salicylic acid (SA), a natural plant defense signal, resulted in an OTR increase. Addition of the defense elicitor Pep13, a cell wall peptide of Phythophthora sojae, induced two distinctive OTR peaks that were higher in SA-primed cells than in unprimed cells upon Pep13 challenge. Both, the OTR increase after priming with SA and the Pep13 challenge were dose-dependent. Furthermore, there was a close correlation of a compound's activity to enhance the oxygen consumption in parsley cells and its capacity to prime Pep13-induced furanocoumarin secretion as evaluated by fluorescence spectroscopy. RAMOS noninvasively determines the OTR as a measure of the metabolic activity of plant cells. Chemical enhancement of oxygen consumption by salicylic derivatives in parsley cell suspension cultures correlates with the induction of the primed state of enhanced defense that enhances the quantity of Pep13-induced furanocoumarin phytoalexins. Treatment with the priming-active compounds methyl jasmonate and pyraclostrobin also resulted in an enhanced respiration activity. Thus, RAMOS is a novel technology for identifying priming-inducing compounds for agriculture.


Quality assurance and temporal stability of a 1.5 T MRI scanner for MR-guided Photon and Particle Therapy.
To describe performance measurements, adaptations and time stability over 20 months of a diagnostic MR scanner for integration into MR-guided photon and particle radiotherapy. For realization of MR-guided photon and particle therapy (MRgRT/MRgPT), a 1.5 T MR scanner was installed at the Heidelberg Ion Beam Therapy Center. To integrate MRI into the treatment process, a flat tabletop and dedicated coil holders for flex coils were used, which prevent deformation of the patient external contour and allow for the use of immobilization tools for reproducible positioning. The signal-to-noise ratio (SNR) was compared for the diagnostic and therapy-specific setup using the flat couch top and flexible coils for the a) head & neck and b) abdominal region as well as for different bandwidths and clinical pulse sequences. Additionally, a quality assurance (QA) protocol with monthly measurements of the ACR phantom and measurement of geometric distortions for a large field-of-view (FOV) was implemented to assess the imaging quality parameters of the device over the course of 20 months. The SNR measurements showed a decreased SNR for the RT-specific as compared to the diagnostic setup of (a) 26% to 34% and (b) 11% to 33%. No significant bandwidth dependency for this ratio was found. The longitudinal assessment of the image quality parameters with the ACR and distortion phantom confirmed the long-term stability of the MRI device. A diagnostic MRI was commissioned for use in MR-guided particle therapy. Using a radiotherapy specific setup, a high geometric accuracy and signal homogeneity was obtained after some adaptions and the measured parameters were shown to be stable over a period of 20 months.


Method for predicting human intestinal first-pass metabolism of UGT substrate compounds.
1. As intestinal glucuronidation has been suggested to generate the low oral bioavailability (F) of drugs, estimating its effects would be valuable for selecting drug candidates. Here, we investigated the absorption and intestinal availability (F(a)F(g)) in animals, and intrinsic clearance via UDP-glucuronosyltransferase (UGT) in intestinal microsomes (CL(int,UGT)) for three drug candidates possessing a carboxylic acid group, in an attempt to estimate the impact of intestinal glucuronidation on F and select potential drug candidates with high F in humans. 2. The F(a)F(g) values of the three test compounds were low in rats and monkeys (0.16-0.51), and high in dogs (≥0.81). Correspondingly, the CL(int,UGT) values were high in rats and monkeys (101-731 µL/min/mg), and low in dogs (≤ 59.6 µL/min/mg). A good inverse correlation was observed between F(a)F(g) and CL(int,UGT), suggesting that intestinal glucuronidation was a major factor influencing F(a)F(g) of these compounds. 3. By applying this correlation to F(a)F(g) in humans using human CL(int,UGT) values (26.9-114 µL/min/mg), compounds 1-3 were predicted to have relatively high F(a)F(g). 4. Our approach is expected to be useful for estimating the impact of intestinal glucuronidation on F in animals and semiquantitatively predicting human F for drug candidates.


Alexa Irene Canady: the first African-American woman neurosurgeon.
The advances of the civil rights movement in the mid-20th century made it possible for many African Americans to have the opportunity to enter the distinguished field of neurosurgery, beginning in 1953 with Clarence S. Greene, Sr. This report details the career and exploits of the first African-American woman neurosurgeon, Alexa Irene Canady, MD. A comprehensive review of pertinent modern and historical records spanning the past century was performed. Born on November 7, 1950, in Lansing, MI, Canady received her MD from the University of Michigan in 1975, graduating with distinction and being elected into the Alpha Omega Alpha Honor Society. Training in neurosurgery under Dr. Shelley Chou from 1976-1981 at the University of Minnesota, she became the program's first female graduate. Following residency, she trained as a pediatric neurosurgery fellow at the Children's Hospital of Philadelphia. In 1984, Canady became the first African-American woman certified by the American Board of Neurological Surgery. She subsequently continued a long, distinguished career in pediatric neurosurgery, first at Henry Ford and later as chief of neurosurgery at Children's Hospital of Michigan before retiring in 2001. Among her many accolades, she was named 1993 Woman of the Year by the American Woman's Medical Association. Canady's diligence, perseverance and commitment enabled her to overcome tremendous odds to become the first African-American woman neurosurgeon, trained at the University of Minnesota. A true pioneer, her achievements have inspired many, opening the door for subsequent women and African Americans to enhance the field of neurosurgery.


A dicentric no. 15 chromosome with two satellite regions.
A case of an inherited chromosome no. 15 with two centromeres and two satellite regions is described and its origin postulated. The chromosome appears to have no clinical significance.


Inhibition of RhoA/Rho kinase pathway and smooth muscle contraction by hydrogen sulfide.
Hydrogen sulfide (H2 S) plays an important role in smooth muscle relaxation. Here, we investigated the expression of enzymes in H2 S synthesis and the mechanism regulating colonic smooth muscle function by H2 S. Expression of cystathionine-γ-lyase (CSE), but not cystathionine-β-synthase (CBS), was identified in the colonic smooth muscle of rabbit, mouse, and human. Carbachol (CCh)-induced contraction in rabbit muscle strips and isolated muscle cells was inhibited by l-cysteine (substrate of CSE) and NaHS (an exogenous H2 S donor) in a concentration-dependent fashion. H2 S induced S-sulfhydration of RhoA that was associated with inhibition of RhoA activity. CCh-induced Rho kinase activity also was inhibited by l-cysteine and NaHS in a concentration-dependent fashion. Inhibition of CCh-induced contraction by l-cysteine was blocked by the CSE inhibitor, dl-propargylglycine (DL-PPG) in dispersed muscle cells. Inhibition of CCh-induced Rho kinase activity by l-cysteine was blocked by CSE siRNA in cultured cells and DL-PPG in dispersed muscle cells. Stimulation of Rho kinase activity and muscle contraction in response to CCh was also inhibited by l-cysteine or NaHS in colonic muscle cells from mouse and human. Collectively, our studies identified the expression of CSE in colonic smooth muscle and determined that sulfhydration of RhoA by H2 S leads to inhibition of RhoA and Rho kinase activities and muscle contraction. The mechanism identified may provide novel therapeutic approaches to mitigate gastrointestinal motility disorders.


Gadolinium Deposition and Chronic Toxicity.
Clinicians, radiologists, and patients should be aware of the most up-to-date data on the risks of gadolinium-based contrast agent (GBCA) administration. In this review, we discuss in vivo gadolinium retention, particularly brain tissue retention, and potential toxic effects. GBCA pharmacokinetics and biodistribution are reviewed briefly. Based on the more recent published literature and society guidelines, general safety recommendations for clinical practice are provided.


Prognostic value of immunotherapy-induced organ inflammation assessed on 18FDG PET in patients with metastatic non-small cell lung cancer.
We evaluated the prognostic value of immunotherapy-induced organ inflammation observed on 18FDG PET in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs). Data from patients with IIIB/IV NSCLC included in two different prospective trials were analyzed. 18FDG PET/CT exams were performed at baseline (PETBaseline) and repeated after 7-8 weeks (PETInterim1) and 12-16 weeks (PETInterim2) of treatment, using iPERCIST for tumor response evaluation. The occurrence of abnormal organ 18FDG uptake, deemed to be due to ICPI-related organ inflammation, was collected. Exploratory cohort (Nice, France): PETInterim1 and PETInterim2 revealed the occurrence of at least one ICPI-induced organ inflammation in 72.8% of patients, including midgut/hindgut inflammation (33.7%), gastritis (21.7%), thyroiditis (18.5%), pneumonitis (17.4%), and other organ inflammations (9.8%). iPERCIST tumor response was associated with improved progression-free survival (p < 0.001). iPERCIST tumor response and immuno-induced gastritis assessed on PET were both associated with improved overall survival (OS) (p < 0.001 and p = 0.032). Combining these two independent variables, we built a model predicting patients' 2-year OS with a sensitivity of 80.3% and a specificity of 69.2% (AUC = 72.7). Validation cohort (Genova, Italy): Immuno-induced gastritis (19.6% of patients) was associated with improved OS (p = 0.04). The model built previously predicted 2-year OS with a sensitivity and specificity of 72.0% and 63.6% (AUC = 70.7) and 3-year OS with a sensitivity and specificity of 69.2% and 80.0% (AUC = 78.2). Immuno-induced gastritis revealed by early interim 18FDG PET in around 20% of patients with NSCLC treated with ICPI is a novel and reproducible imaging biomarker of improved OS.


Formation of ammonia-helium compounds at high pressure.
Uranus and Neptune are generally assumed to have helium only in their gaseous atmospheres. Here, we report the possibility of helium being fixed in the upper mantles of these planets in the form of NH3-He compounds. Structure predictions reveal two energetically stable NH3-He compounds with stoichiometries (NH3)2He and NH3He at high pressures. At low temperatures, (NH3)2He is ionic with NH3 molecules partially dissociating into (NH2)- and (NH4)+ ions. Simulations show that (NH3)2He transforms into intermediate phase at 100 GPa and 1000 K with H atoms slightly vibrate around N atoms, and then to a superionic phase at ~2000 K with H and He exhibiting liquid behavior within the fixed N sublattice. Finally, (NH3)2He becomes a fluid phase at temperatures of 3000 K. The stability of (NH3)2He at high pressure and temperature could contribute to update models of the interiors of Uranus and Neptune.


The Common Femoral Artery Is a Fixed Arterial Segment.
The risk of stent fracture caused by the movements of the hip joint is one of the limitations of the endovascular treatment of the common femoral artery (CFA). The aim of this study was to describe and analyze the deformations of the iliofemoral axis during flexion and extension of the hip, and to evaluate the impact of stents implanted in the CFA on the deformations observed. This monocentric descriptive study was carried out on the pelvis obtained from three fresh cadavers (two men aged 72 and 71 years, respectively, and one 94-year-old woman). Arteriography was carried out to appreciate the deformations of the external iliac and common femoral arteries, and to analyze the femoral junctions. A first arteriography was carried out on native arteries, and a second one was carried out after the implantation of a stent in the CFA (Zilver PTX, Cook Medical, Bloomington, IN, USA). In all the cases, anterior and lateral images were obtained, with the hip maintained in extension (0°) or flexion (45°, 90°). In a neutral position (extension), four points of deformation of the iliofemoral axis were identified in the frontal (A, B, C, and D) and sagittal (A', B', C', D') planes. These points were the vertices of the angles formed by the arterial deformation in the frontal and sagittal planes. These four points of deformation observed in the two planes appeared overlapping (A/A', B/B', C/C', and D/D') and were located on the external iliac artery, the origin of the CFA, the femoral bifurcation and the superficial femoral artery, respectively. In the frontal plane, all the angles closed during flexion, and the closure of the angle increased with the degree of flexion. In the sagittal plane, we observed that the angles with the A', C', and D' vertices closed during the flexion of the hip, and that the angle with the B' vertex opened during flexion. The higher was the degree of flexion, the more the angles were accentuated. The implantation of one stent in the CFA modified neither the localization of the points of deformation nor the modifications of angles previously observed on the frontal and the sagittal sections. As seen from the front and side, the CFA is a fixed segment during the movements of extension and flexion of the hip. The implantation of a stent does not modify this observation.


Cell survival pathways targeted in rare lung disease affecting women.
Novel drug targets are identified in lymphangioleiomyomatosis (LAM), a rare disease in women. These targets focus on uterine transcription factors necessary for LAM cell survival.


Relation of reperfusion success with anistreplase or alteplase in acute myocardial infarction to body weight. The TEAM-3 investigators.
Adjustment in dose based on body size is not recommended currently for thrombolytic regimens, except for a reduction in alteplase (recombinant tissue-type plasminogen activator [rt-PA]) dose for safety reasons in patients with low body weight. It is unresolved how to dose thrombolytic agents in very heavy patients. The study objective was to assess whether patency of the infarct-related artery at 1 day after therapy with anistreplase (anisoylated plasminogen streptokinase activator complex [APSAC]) or rt-PA is adversely affected by increased body weight. Data were analyzed from a double-blind, randomized, comparative study of APSAC (30 U/5 min) versus rt-PA (100 mg/3 hours, adjusted downward for body weight < 65 kg), together with heparin and aspirin, in patients with acute myocardial infarction presenting within 4 hours of symptom onset. Coronary patency, determined at 1 day, was assessed in a blinded fashion, and patency success was correlated with body weight, divided into quintiles. In patients treated with APSAC, coronary patency rates were similar in those in the upper quintile of body weight (> 94 kg; n = 22) and in the low-normal weight group (n = 126) (86 and 90%, respectively, for perfusion grade 2/3 [p = 0.64]; and 82 and 74%, respectively, for grade 3 [p = 0.42]). In contrast, for the rt-PA group, heavy patients (n = 34) achieved significantly lower patency rates (74 vs 89% for grade 2/3 [p = 0.02]; and 59 vs 77% for grade 3 [p = 0.03]). The dose of heparin administered, adjusted to maintain a therapeutic partial thromboplastin time until the 1-day (mean 28 hours) angiogram, was greater in the heavy than in the low-normal weight group (mean +/- SE 39,680 +/- 4,818 vs 30,027 +/- 1,177 U; p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)


Physiological Ca2+ level and Ca2+-induced Permeability Transition Pore control protein phosphorylation in rat brain mitochondria.
Phosphorylation of several low molecular mass proteins (3.5, 17, 23 and 29kDa) was observed in rat brain mitochondria (RBM) at ATP concentration close to that in the mitochondrial matrix. Furthermore, regulatory effects of Ca2+ on phosphorylation of these proteins were investigated. Protein phosphorylation was found to be modulated by Ca2+ in the physiological concentration range (10(-8) to 10(-6)M free Ca2+). Incorporation of 32P from [gamma-32P]ATP into the 17kDa protein was dramatically increased within the 10(-7) to 10(-6)M free Ca2+ range, whereas an opposite effect was observed for the 3.5kDa polypeptide. Strong de-phosphorylation of the 3.5kDa polypeptide and enhanced 32P-incorporation into the 17 and 23kDa proteins were found with supra-threshold Ca2+ loads and these effects were eliminated or reduced in the presence of cyclosporin A, an inhibitor of Permeability Transition Pore (PTP) opening. In the presence of calmidazolium (Cmz), a calmodulin antagonist, enhanced levels of phosphorylation of the 17 and 3.5kDa polypeptides were observed and the 17kDa protein phosphorylation was suppressed by H-8, a protein kinase A inhibitor. It is concluded that Ca2+ in physiological concentrations, as a second messenger, can control phosphorylation of the low molecular mass phospoproteins in RBM, in addition to well known regulation of some Krebs cycle dehydrogenases by Ca2+. The protein phosphorylation was strongly dependent on the Ca2+-induced PTP opening.


The importance of 'neighbourhood' in the persistence of bovine tuberculosis in Irish cattle herds.
Local persistence of infection is a key feature of bovine tuberculosis (bTB) among cattle herds in the Republic of Ireland. The aim of this study was to determine the relative importance of 'neighbourhood', specifically farm-to-farm spread and spread from wildlife, in the persistence of bTB by investigating herds having a bTB episode in 2006. A case-control study was conducted on the association between the occurrence of a bTB episode in 2006 and the occurrence of bTB in previous years among neighbouring herd(s) within 1 km, while controlling for each herd's bTB history and other risk factors. Neighbouring herds were grouped into three zones, based on distance, and bTB incidence measures summarised within each zone and by calendar year (2001-2005). The incidence of bTB was associated with an increased animal incidence in two subsets of neighbouring herds: (i) herds directly contiguous during the previous 2 years (attributable fraction=0.20), and (ii) herds at a distance of >25 m in the previous year (attributable fraction=0.19). Other predictors of bTB in a herd in 2006 included the occurrence of a bTB episode within that herd in any of the previous 5 years, herd size, and the number of animals purchased at age greater than 12 months. An infected wildlife source best explains the existence of a "neighbouring herd risk" for bTB at distances greater than 25 m. Further studies will be necessary to determine to what extent neighbouring herd risk within 25 m may be confounded by the same wildlife (badger) source.


Comparative roles of free fatty acids with reactive nitrogen intermediates and reactive oxygen intermediates in expression of the anti-microbial activity of macrophages against Mycobacterium tuberculosis.
We assessed the role of free fatty acids (FFA) in the expression of the activity of macrophages against Mycobacterium tuberculosis in relation to the roles of two major anti-microbial effectors, reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI). Intracellular growth of M. tuberculosis residing inside macrophages was accelerated by treatments of macrophages with either quinacrine (phospholipase A2 (PLA2) inhibitor), arachidonyl trifuloromethylketone (type IV cytosolic PLA2 inhibitor), NG-monomethyl-L-arginine (nitric oxide synthase inhibitor), and superoxide dismutase plus catalase (ROI scavengers). In addition, M. tuberculosis-infected macrophages produced and/or secreted these effectors sequentially in the order ROI (0-3 h), FFA (0-48 h), and RNI (3 to at least 72 h). Notably, membranous FFA (arachidonic acid) of macrophages translocated to M. tuberculosis residing in the phagosomes of macrophages in phagocytic ability- and PLA2-dependent fashions during cultivation after M. tuberculosis infection. FFA, RNI and H2O2-mediated halogenation system (H2O2-halogenation system) displayed strong activity against M. tuberculosis in cell-free systems, while ROI alone exerted no such effects. Combinations of 'FFA + RNI' and 'RNI + H2O2-halogenation system' exhibited synergistic and additive effects against M. tuberculosis, respectively, while 'FFA + H2O2-halogenation system' had an antagonistic effect. Moreover, a sequential attack of FFA followed by RNI exerted synergistic activity against M. tuberculosis. Since M. tuberculosis-infected macrophages showed simultaneous production of RNI with FFA secretion for relatively long periods (approx. 45 h) and prolonged RNI production was seen thereafter, RNI in combination with FFA appear to play critical roles in the manifestation of the activity of macrophages against M. tuberculosis.


Scale-free vertical tracking microscopy.
The behavior and microscale processes associated with freely suspended organisms, along with sinking particles underlie key ecological processes in the ocean. Mechanistically studying such multiscale processes in the laboratory presents a considerable challenge for microscopy: how to measure single cells at microscale resolution, while allowing them to freely move hundreds of meters in the vertical direction? Here we present a solution in the form of a scale-free, vertical tracking microscope, based on a 'hydrodynamic treadmill' with no bounds for motion along the axis of gravity. Using this method to bridge spatial scales, we assembled a multiscale behavioral dataset of nonadherent planktonic cells and organisms. Furthermore, we demonstrate a 'virtual-reality system for single cells', wherein cell behavior directly controls its ambient environmental parameters, enabling quantitative behavioral assays. Our method and results exemplify a new paradigm of multiscale measurement, wherein one can observe and probe macroscale and ecologically relevant phenomena at microscale resolution. Beyond the marine context, we foresee that our method will allow biological measurements of cells and organisms in a suspended state by freeing them from the confines of the coverslip.


Effect of RNAi-induced down regulation of nuclear factor kappa-B p65 on acute monocytic leukemia THP-1 cells in vitro and vivo.
NF-κB p65 is found constitutively active in acute monocytic leukemia, and has been considered an important factor for poor prognosis. Therefore, develop specifically target p65 inhibitors will be substantial interest. Until now, although several p65 inhibitors are currently in preclinical and clinical development, none of them are targeting. In this study, siRNA targeting p65 was introduced into the acute monocytic leukemia cell line THP-1 and THP-1 xenograft tumors in nude mice, and then, we measured p65 mRNA and protein levels by real-time RT-PCR and Western blotting, and levels of related protein cyclin D1, Bc1-2, and SMRT by Western blotting. We also investigated the cell cycle and apoptosis via FCM, and cell proliferation by Cell Counting Kit-8 assay. We found that p65 siRNA could effectively reduce the p65 mRNA and protein expression, arrest cells in G0/G1 phase, inhibit the proliferation and increase the apoptosis of THP-1 cells, and intratumoral injection of p65 siRNA could suppress tumor growth in nude mice. We also found that when down regulation of p65, the expression of cyclin D1 and Bc1-2 decreased, and the expression of SMRT increased in vitro and vivo. All these findings suggest that NF-κB p65 maybe an attractive candidate for the therapeutic targeting of acute monocytic leukemia.


Acceptor substrate discrimination in phosphatidyl-myo-inositol mannoside synthesis: structural and mutational analysis of mannosyltransferase Corynebacterium glutamicum PimB'.
Long term survival of the pathogen Mycobacterium tuberculosis in humans is linked to the immunomodulatory potential of its complex cell wall glycolipids, which include the phosphatidylinositol mannoside (PIM) series as well as the related lipomannan and lipoarabinomannan glycoconjugates. PIM biosynthesis is initiated by a set of cytosolic α-mannosyltransferases, catalyzing glycosyl transfer from the activated saccharide donor GDP-α-D-mannopyranose to the acceptor phosphatidyl-myo-inositol (PI) in an ordered and regio-specific fashion. Herein, we report the crystal structure of mannosyltransferase Corynebacterium glutamicum PimB' in complex with nucleotide to a resolution of 2.0 Å. PimB' attaches mannosyl selectively to the 6-OH of the inositol moiety of PI. Two crystal forms and GDP- versus GDP-α-d-mannopyranose-bound complexes reveal flexibility of the nucleotide conformation as well as of the structural framework of the active site. Structural comparison, docking of the saccharide acceptor, and site-directed mutagenesis pin regio-selectivity to a conserved Asp residue in the N-terminal domain that forces presentation of the correct inositol hydroxyl to the saccharide donor.


The effects of a polystyrene nanoplastic on the immune response and gut microbiota of Eriocheir sinensis and its post-recovery state.
Although there is increasing concern about the toxicity of nanoplastics, the effects of nanoplastic exposure and subsequent recovery on immune responses, as well as antioxidant responses and gut microbiota, in crustaceans are rarely reported. In this study, the nonspecific immunity and antioxidant defense of Eriocheir sinensis were evaluated after acute exposure to various concentrations (0, 2.5, 5, 10 and 20 mg/L) of 75-nm polystyrene nanoplastics (PS-NPs) for 48 h, as well as after 7 days of recovery from the nanoplastic environment. The results showed that, after 48 h of exposure, nanoplastics were observed in the gills, hepatopancreas and gut. However, no nanoplastics were found in the gut after 7 days of recovery. Under nanoplastic-induced stress, Hc, Relish, proPO, and LITAF mRNA levels increased in the gills and hepatopancreas for 48 h. Expression of the myd88, Hc, Relish and proPO genes decreased in the gills during the 7-day recovery period. Exposure to nanoplastics for 48 h and recovery for 7 days significantly decreased the activities of lysozyme (LZM) alkaline phosphatase (AKP), total superoxide dismutase (SOD) and phenoloxidase (POD) and, glutathione peroxidase (GPX) in the hepatopancreas. Meanwhile, the relative abundance of pathogens exposed to 10 mg/L nanoplastics for 48 h increased at the species level, and these pathogens decreased significantly in the 7-day recovery period. These results suggested that exposure to nanoplastics for 48 h affected the activities of immune system enzymes and expression of immune-related genes in Eriocheir sinensis and altered the diversity and composition of their gut microbiota. E. sinensis could not recover from damage to the hepatopancreas within a 7-day recovery period. The results of this study provided insight into the effects of nanoplastics on crustaceans and it filled a gap in research on crustacean recovery after exposure to nanoplastics.


Aromatic alcohols as neuroprotectants.
Free radicals and oxidative stress-induced neuronal cell death have been implicated in various neurological disorders including neurodegenerative diseases. We have recently shown that estrogens can protect neurons against oxidative stress due to their antioxidant potential. Here, we report that also other aromatic alcohols with intact phenolic groups and different phenol derivatives can protect neurons against oxidative cell death as induced by glutamate and hydrogen peroxide. Starting with melatonin, in this study, we degraded the chemical structure step by step and tested various aromatic alcohols as well as phenol derivatives for their potential antioxidant activity. We found that aromatic alcohols with intact phenolic groups protect neurons effectively against oxidative damage and cell death and that this neuroprotective activity is independent of the time the compound is added before the toxin. Methylation of the phenolic hydroxyl group led to a decrease or loss in neuroprotection. Moreover, the tested compounds directly inhibited peroxidation reactions suggesting that the neuroprotection is mediated by antioxidant properties. Our result may have some impact on the design of future drugs for the antioxidant treatment or prevention of oxidative stress-associated pathological conditions.


Use of arterialised venous instead of arterial blood for measurement of myocardial glucose metabolism during euglycaemic-hyperinsulinaemic clamping.
Sampling of arterialised venous blood (AVB) is often used as an alternative to sampling of arterial blood when determining the myocardial metabolic rate of glucose (MRGlu). This method, however, has not yet been validated for measurement of plasma fluorine-18 fluorodeoxyglucose (FDG) activity during a euglycaemic-hyperinsulinaemic clamp (EHC). In this study, dynamic FDG scans were performed with arterial blood sampling during EHC. Samples of arterial and AVB or venous blood were simultaneously withdrawn at five time points for measurement of FDG activity and plasma glucose in 36 patients. Both venous to arterial and AVB to arterial ratios were calculated for FDG activity and plasma glucose. Mean ratios between AVB and arterial FDG activity were then used to create calculated arterialised venous input functions from corresponding arterial input functions. The mean effect of arterialisation on the calculation of K(i) was assessed. In nine additional patients, K(i) obtained with continuous sampling of AVB was compared with K(i) obtained with a corresponding (quality-controlled) image-derived input function from the ascending aorta. Using AVB, measurements of FDG activity were much more reliable than with venous blood sampling. As compared with arterial sampling, however, FDG activity was underestimated early after injection, while it was overestimated after 20 min. In both analyses, AVB resulted in approximately 10%+/-10% overestimation of K(i). Because of a 5%+/-5% underestimation of plasma glucose concentration with AVB, the net effect on the final calculation of MRGlu was small (on average 5% overestimation). It is concluded that the use of AVB has a small average effect on the determination of MRGlu. This method does, however, contribute to variability in the results. This variability cannot be explained by different degrees of arterialisation.


Influence of moisture and amylose on the physicochemical properties of rice starch during heat treatment.
Moisture and amylose are important factors affecting the quality of heat-treated starches. The amylose content in heat-treated rice starch increased as moisture content (MC) increased from 8% to 30%, but decreased at MC of 70%. With the increase of MC, the paste transmittance, gelatinization temperature, and digestibility of starch increased, whereas the swelling power and enthalpy decreased. The long- and short-range molecular order and the digestive properties of starch with MC ≤ 30% changed moderately, but high MC (70%) gelatinized the starch and drastically changed the physicochemical properties. High amylose content in rice starch led to low long- and short-range molecular order, swelling power, and gelatinization temperature, but increased resistant starch. The results indicated that 30% of MC separates effects of heat treatment of starch, where low MC (≤30%) and high amylose lowers digestibility, which is beneficial for diabetics, while high MC (>30%) promotes solubility and transparency.


Vitality markers in forensic investigations: a literature review.
Determining whether an injury was sustained in life or not is one of the most important topics in forensic medicine. Morphological, cytological, and biological techniques are used to assess wound vitality. Several markers involved in vital and supravital reactions increase the accuracy of wound age estimation. This systematic review aimed to investigate the main vitality markers used in forensic medicine to date. This review was conducted by performing a systematic literature search on online resources (PubMed Central database and Google Scholar) until May 2022. We identified 46 articles published between 1987 and May 2022, analyzing a total of 53 markers. Based on the data of this review, the most studied vitality markers were adhesion molecules (fibronectin, p-selectin, CD 15), pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), cathepsin D, tryptase, and microRNAs (miRNAs). The most interesting studies were based on animal models: the different markers were investigated through immunohistochemical and qRT-PCR methods. The experimental methods were usually based on skin incisions, ligature marks, and burned skin areas. To date, it has not been possible to identify any gold standard markers based on the criteria of efficacy, specificity, and reliability; however, studies are still in progress. In the future, the use of miRNAs is promising as well as the combination of multiple markers. In this way, it will be possible to increase the sensitivity and specificity to validate systems or models for determining wound vitality in forensic practice.


Accuracy of Controlled Attenuation Parameter and Liver Stiffness Measurement in Patients with Non-alcoholic Fatty Liver Disease.
We evaluated the diagnostic accuracy of the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) measured with either an M or XL probe against liver biopsy (LB) in patients with non-alcoholic fatty liver disease (NAFLD). This study was a cross-sectional prospective study that included 179 NAFLD patients. With a cutoff value for CAP ≥345, we can exclude significant steatosis in 87% (79.4%-92.5%) of our population. With respect to the LSM, the highest accuracy was obtained for F ≥ F3 (area under the receiver operating characteristic curve [AUROC] = 0.98) and F = F4 (AUROC = 0.98). In a multivariable linear regression model, significant predictors influencing LSM were fibrosis stage (β = 2.6, p < 0.001) as a positive predictor and lobular inflammation (β = -0.68, p = 0.04) as a negative predictor, without significant influence after adjustment for CAP and probe type. We found that CAP is a satisfactory method for excluding advanced steatosis, while LSM is a good non-invasive marker for the exclusion of fibrosis.


Transthyretin inhibition of amyloid beta aggregation and toxicity.
The aim of this study was to investigate transthyretin (prealbumin) effects on Abeta25-35-induced cytotoxicity. In view of the well-recognized literature data demonstrating that Abeta25-35 fibrillar aggregates cause in vitro cytotoxicity to human red blood cells and apoptotic changes to SK-N-BE neuroblastoma cells in cultures (ultrastructural evidence), we tested transthyretin effects on these two experimental models. Incubation of Abeta25-35 with transthyretin (at transthyretin concentrations equal to CSF physiological levels) demonstrated both inhibition of red blood cells lysis and neutralization of SK-N-BE neuroblastoma cells ultrastructural apoptotic changes. Moreover, transthyretin was shown to be able to inhibit the formation of fibrillar macroaggregates of Abeta25-35. The findings imply that experimental systems investigating Abeta-induced cytotoxicity consider the protective interaction of transthyretin with Abeta; an interaction to be considered also in vivo in view of the fact that transthyretin immunoreactivity has been previously demonstrated in amyloid plaques of brains from Alzheimer's disease patients.


SPECT/CT imaging of HER2 expression in colon cancer-bearing nude mice using 125I-Herceptin.
An accurate assessment of HER2 status in patients with colorectal cancer is very important, because only the patients overexpressing HER2 can benefit most from the anti-HER2 targeted therapy. In this study, we investigated the feasibility of detecting HER2 expression in colon cancer by SPECT imaging using 125I-Herceptin, which showed high labeling rate, good in vitro stability and high binding specificity for HER2. HER2-positive mouse colon adenocarcinoma cell line (MC 38) was chosen as the colon caner cell model, and used for the establishment of colon cancer-bearing nude mice model. SPECT/CT imaging suggested that the tumors can be visualized at 12 h after the injection of 125I-Herceptin, and the uptake of tracer in tumors reached the peak at 24 h after injection, and can be attenuated significantly by pretreatment with an excess of nonlabeled Herceptin. These results indicates that 125I-Herceptin can be considered as an effective SPECT probe for the non-invasive detection of HER2 expression in colon cancer.


Analysis of neurofibromatosis 1 (NF1) lesions by body segment.
Café-au-lait spots and neurofibromas are defining features of neurofibromatosis 1 (NF1), but they vary greatly in number, size, and clinical importance from patient to patient. The cause of this variability is unknown. We tested the hypotheses that development of these lesions is influenced by local or familial factors. The presence or absence of café-au-lait spots, cutaneous neurofibromas, and diffuse plexiform neurofibromas was recorded for each of 10 divisions of the body surface in 547 NF1 patients, including 117 affected individuals in 52 families. We used stratified Mantel-Haenszel tests to look for local associations between the presence of diffuse plexiform neurofibromas, cutaneous neurofibromas, and café-au-lait spots in individual body segments of NF1 patients. We used a random effects model to obtain intrafamilial correlation coefficients for the age-adjusted number of body divisions affected with each of the three lesions. No significant association was observed between the occurrence of cutaneous and diffuse plexiform neurofibromas, between café-au-lait spots and cutaneous neurofibromas, or between café-au-lait spots and plexiform neurofibromas in the same body segment. The correlation among relatives in the number of body segments affected with café-au-lait spots was 0.45 (95% confidence interval [CI] = 0.18-0.71), with cutaneous neurofibromas, 0.37 (95% CI = 0.15-0.55), and with plexiform neurofibromas, 0.35 (95% CI = 0.15-0.57). We conclude that the development of café-au-lait spots, cutaneous neurofibromas, and plexiform neurofibromas are spatially independent in NF1 patients but that the development of all three lesions is influenced by familial factors.


Bioengineered glaucomatous 3D human trabecular meshwork as an in vitro disease model.
Intraocular pressure (IOP) is mostly regulated by aqueous humor outflow through the human trabecular meshwork (HTM) and represents the only modifiable risk factor of glaucoma. The lack of IOP-modulating therapeutics that targets HTM underscores the need of engineering HTM for understanding the outflow physiology and glaucoma pathology in vitro. Using a 3D HTM model that allows for regulation of outflow in response to a pharmacologic steroid, a fibrotic state has been induced resembling that of glaucomatous HTM. This disease model exhibits HTM marker expression, ECM overproduction, impaired HTM cell phagocytic activity and outflow resistance, which represent characteristics found in steroid-induced glaucoma. In particular, steroid-induced ECM alterations in the glaucomatous model can be modified by a ROCK inhibitor. Altogether, this work presents a novel in vitro disease model that allows for physiological and pathological studies pertaining to regulating outflow, leading to improved understanding of steroid-induced glaucoma and accelerated discovery of new therapeutic targets. Biotechnol. Bioeng. 2016;113: 1357-1368. © 2015 Wiley Periodicals, Inc.


Changes in jugular bulb oxygen saturation during off-pump coronary artery bypass graft surgery.
The effect of haemodynamic derangement during coronary artery anastomosis in off-pump coronary artery bypass surgery on cerebral blood flow has not been elucidated. Jugular bulb oxygen saturation is a useful indicator of cerebral blood flow provided that the cerebral metabolic rate is constant. This study was designed to evaluate the changes in jugular bulb oxygen saturation during off-pump coronary artery bypass surgery. With IRB approval, 48 patients were included. After anaesthesia, an 18-G catheter was introduced into the jugular bulb. Haemodynamic variables and oxygen profiles from gas analysis of jugular bulb blood and arterial blood were obtained: after sternotomy (baseline); at 5 min after the beginning of the anastomosis of the left anterior descending artery, obtuse marginal artery, and right coronary artery; and after sternal closure. Cardiac index and mixed venous oxygen saturation decreased significantly during anastomosis of all three arteries compared to the baseline value. Although the changes in jugular bulb oxygen saturation during anastomosis were statistically significant compared to its baseline value, jugular bulb oxygen saturation remained within normal limit throughout the study. Jugular bulb oxygen saturation, which represents the global cerebral oxygenation, was well maintained during the anastomosis of all coronary arteries despite significant haemodynamic changes during off-pump coronary artery bypass (OPCAB).


Trends of hepatitis B and hepatitis C mortality in Canada, 1979-1997.
Mortality data from Statistics Canada were analyzed to measure the temporal trends and burden of illness attributed to viral hepatitis in Canada. Analysis of age-standardized mortality rates from 1979 to 1997 showed an increasing trend in mortality for both hepatitis B and non-A, non-B hepatitis (NANBH), most of which are attributed to hepatitis C infections. Hepatitis B and NANBH age-standardized mortality rates increased respectively, from 0.03 and 0.12 deaths per 100,000 population in 1979 to 0.26 and 0.41 deaths per 100,000 in 1997. Male mortality rates were consistently higher than female for both diseases. Among deaths from chronic liver disease, over 1,000 deaths were estimated to have been caused by hepatitis B and hepatitis C annually. Although the hepatitis B or NANBH recorded deaths largely underestimate the true burden of HBV and HCV in Canada, the temporal trends are useful as they reflect changes in the impact of both diseases.


Assessment of successful valve reconstruction by intraoperative transesophageal echocardiography (TEE).
In 17 patients (10 patients with mitral insufficiency, 5 patients with tricuspid regurgitation, 2 patients with mitral stenosis) the result of valve reconstruction was evaluated by intraoperative two-dimensional transesophageal contrast-echocardiography (TEE). Therefore, 1-2cc of an agitated contrast-medium (Gelifundol) were injected into the left or right ventricle. The result of reconstruction was assessed by the extent of regurgitant microbubbles into the left or right atrium. A successful valve repair could be demonstrated in 15 patients without or with only minimal regurgitation of contrast-fluid. In one patient residual severe mitral insufficiency after valve reconstruction could only be detected when valve function was examined by contrast-TEE in the beating heart. An intraoperative decision for valve replacement was made. In another patient, mild to moderate residual mitral incompetence was shown; no further surgical intervention was done. By TEE the function of reconstructed valves can be examined under physiological conditions in the beating heart. Surgeons can obtain additional intra-operatively information and certainty about the result of reconstruction and an early decision for valve replacement can be made if necessary.


Machine learning algorithms for predicting days of high incidence for out-of-hospital cardiac arrest.
Predicting out-of-hospital cardiac arrest (OHCA) events might improve outcomes of OHCA patients. We hypothesized that machine learning algorithms using meteorological information would predict OHCA incidences. We used the Japanese population-based repository database of OHCA and weather information. The Tokyo data (2005-2012) was used as the training cohort and datasets of the top six populated prefectures (2013-2015) as the test. Eight various algorithms were evaluated to predict the high-incidence OHCA days, defined as the daily events exceeding 75% tile of our dataset, using meteorological and chronological values: temperature, humidity, air pressure, months, days, national holidays, the day before the holidays, the day after the holidays, and New Year's holidays. Additionally, we evaluated the contribution of each feature by Shapley Additive exPlanations (SHAP) values. The training cohort included 96,597 OHCA patients. The eXtreme Gradient Boosting (XGBoost) had the highest area under the receiver operating curve (AUROC) of 0.906 (95% confidence interval; 0.868-0.944). In the test cohorts, the XGBoost algorithms also had high AUROC (0.862-0.923). The SHAP values indicated that the "mean temperature on the previous day" impacted the most on the model. Algorithms using machine learning with meteorological and chronological information could predict OHCA events accurately.


In vitro effects of pollutants from particulate and volatile fractions of air samples-day and night variability.
Chemicals in air were characterized for potential interference with signaling of estrogen, androgen, and arylhydrocarbon (AhR) receptors, which are known to play an important role in endocrine-disruptive changes in vivo. Previously, effects of this type have been studied mainly in particulate matter in the ambient air from various localities. In this study, both volatile and particulate fractions of air from three sites in Banja Luka region (Bosnia and Herzegovina) were investigated to describe the distribution of endocrine-disrupting contaminants on a small spatial scale. Circadian variability of air pollution was investigated by collecting samples during both day and night. Air samples collected from urban localities at night were more potent in producing the AhR-mediated effects than those collected during daytime. This trend was not observed at the reference rural location. None of the samples showed significant estrogenic or androgenic activity. On the other hand, anti-androgenicity was detected in both particulate and vapor phases, while anti-estrogenicity was detected only in the particulate fraction of air from all localities. The AhR-mediated potencies of samples were associated primarily with non-persistent compounds. Based on the concentrations of 28 individual compounds, PAHs accounted for approximately 30 % of the AhR-mediated potency determined by the bioassay. The results show that there can be a significant difference between levels of bioactive compounds in air between daytime and nighttime.


Outcomes of patients with myocardial infarction and cardiogenic shock treated with culprit vessel-only versus multivessel primary PCI.
Multivessel primary percutaneous coronary intervention (pPCI) is still often used in patients with ST-elevation myocardial infarction (STEMI) and cardiogenic shock (CS). The study aimed to compare the characteristics and prognosis of patients with CS-STEMI and multivessel coronary disease (MVD) treated with culprit vessel-only pPCI or multivessel-pPCI during the initial procedure. From 2016 to 2020, 23,703 primary PCI patients with STEMI were included in a national all-comers registry of cardiovascular interventions. Of them, 1,213 (5.1%) patients had CS and MVD at admission to the hospital. Initially, 921 (75.9%) patients were treated with culprit vessel (CV)-pPCI and 292 (24.1%) with multivessel (MV)-pPCI. Patients with 3-vessel disease and left main disease had a higher probability of being treated with MV-pPCI than patients with 2-vessel disease and patients without left main disease (28.5% vs. 18.6%; p < 0.001 and 37.7% vs. 20.6%; p < 0.001). Intra-aortic balloon pump, extracorporeal membrane oxygenation (ECMO), and other mechanical circulatory support systems were more often used in patients with MV-pPCI. Thirty (30)-day and 1-year all-cause mortality rates were similar in the CV-pPCI and MV-pPCI groups (odds ratio, 1.01; 95% confidence interval [CI] 0.77 to 1.32; p = 0.937 and 1.1; 95% CI 0.84 to 1.44; p = 0.477). The presence of 3-vessel disease and the use of ECMO were the strongest adjusted predictors of 30-day and 1-year mortality. Our data from an extensive all-comers registry suggests that selective use of MV-pPCI does not increase the all-cause mortality rate in patients with CS-STEMI and MVD compared to CV-pPCI.


IVT CCK-8 is more effective than IV CCK-8 at decreasing meal size in the baboon.
In this study, we compared the effectiveness of intravenous (IV) vs. intraventricular (IVT) cholecystokinin octapeptide (CCK-8) to decrease single meal size over a dose range of 0.1 to 4.0 micrograms/kg in a population of overnight fasted baboons. IV CCK did not decrease meal size significantly at doses of 0.5, 1, and 4 micrograms/kg (84 +/- 22%, 78 +/- 12%, and 89 +/- 33% of paired control meal sizes respectively). IVT CCK significantly decreased single meal size at all doses tested (40 +/- 18%, 26 +/- 10%, 37 +/- 15%, 26 +/- 12%, and 12 +/- 6% of paired control meal sizes at 0.1, 0.25, 0.5, 1, and 2 micrograms/kg respectively). Meal suppression with IVT CCK was significantly greater than that achieved with IV CCK at doses of 1 and 2 micrograms/kg. We conclude that in the baboon, CCK may have a direct effect at the central nervous system to suppress single meal size.


Terephthalamide derivatives as mimetics of the helical region of Bak peptide target Bcl-xL protein.
A group of novel Bcl-xL/Bak antagonists, based on a terephthalamide scaffold, were designed to mimic the alpha-helical region of the Bak peptide. Good in vitro inhibition potencies in disrupting the Bak/Bcl-xL complex have been observed (terephthalamide 4, K(i)=0.78+/-0.07 microM).


An actin-destabilizing factor is present in human plasma.
Plasma and serum of humans or experimental animals contain a factor which destabilizes F-actin. The factor has no DNAse or thrombin activity and after incubation with F-actin does not modify the position of the actin band on a SDS polyacrylamide gel. Hence it probably depolymerizes F-actin.


The plant-growth-promoting actinobacteria of the genus Nocardia induces root nodule formation in Casuarina glauca.
Actinorhizal plants form a symbiotic association with the nitrogen-fixing actinobacteria Frankia. These plants have important economic and ecological benefits including land reclamation, soil stabilization, and reforestation. Recently, many non-Frankia actinobacteria have been isolated from actinorhizal root nodules suggesting that they might contribute to nodulation. Two Nocardia strains, BMG51109 and BMG111209, were isolated from Casuarina glauca nodules, and they induced root nodule-like structures in original host plant promoting seedling growth. The formed root nodule-like structures lacked a nodular root at the apex, were not capable of reducing nitrogen and had their cortical cells occupied with rod-shaped Nocardiae cells. Both Nocardia strains induced root hair deformation on the host plant. BMG111209 strain induced the expression of the ProCgNin:Gus gene, a plant gene involved in the early steps of the infection process and nodulation development. Nocardia strain BMG51109 produced three types of auxins (Indole-3-acetic acid [IAA], Indole-3-Byturic Acid [IBA] and Phenyl Acetic Acid [PAA]), while Nocardia BMG111209 only produced IAA. Analysis of the Nocardia genomes identified several important predicted biosynthetic gene clusters for plant phytohormones, secondary metabolites, and novel natural products. Co-infection studies showed that Nocardia strain BMG51109 plays a role as a "helper bacteria" promoting an earlier onset of nodulation. This study raises many questions on the ecological significance and functionality of Nocardia bacteria in actinorhizal symbioses.


Health-promoting behavior among undergraduate students in the COVID-19 era: Its association with problematic use of social media, social isolation, and online health information-seeking behavior.
To examine the association between problematic use of social media, online health information-seeking, social isolation, and health-promoting behaviors among Korean undergraduate students. In total, 178 undergraduate students participated in this study. A multiple linear regression analysis was performed. Predictors of health-promoting behaviors included overall time spent on social media, problematic social media use, social isolation, and online information-seeking, explaining 33.5 % of the variance in health-promoting behaviors. Prolonged social media use and social isolation negatively affected undergraduate students' health-promoting behaviors, while online information-seeking positively affected them. Nurses should assist young adults in improving health-promoting behaviors by preventing problematic social media uses, reducing social isolation, and strengthening their online health information-seeking ability.


Impact of COVID-19 on Teaching the Tooth Morphology Course to the New Generation of Learners: A Cross-sectional Study.
The purpose of the study was two-fold. First, to evaluate students' learning style and relate it to their academic performance. Second, to highlight changes implemented in the tooth morphology (TOMO) course as a response to the coronavirus disease-2019 (COVID-19) pandemic. The study was performed during 2021-2022 with 101 dental students. Didactic lectures were delivered online and students challenged with nine quizzes and one final examination. Didactic score was calculated by averaging the scores of quizzes and the final exam. Lab score was a combination of five lab projects and the final competency. At course completion, students received a survey on their learning style and how they would like to receive feedback. Kruskal-Wallis test was used to assess differences in didactic and lab scores among groups. Many students perceived themselves as visual learners (39%) followed by kinesthetic (24%), aural (19%), and reader (18%). There was no difference among learning style groups in performance of didactic (p = 0.340) and lab scores (p = 0.845). Students preferred that the instructor talks them through the questions for feedback on quizzes (41%) while they preferred demonstrations when receiving feedback on their wax-ups (51%). Most students (75%) preferred a TOMO teacher that uses demonstrations. 2020-2021 marked the year of the pandemic where all lectures were delivered online and waxing projects were performed at-home. A postpandemic transformation occurred during 2021-2022, reverting to conventional in-person lab sessions while keeping online didactic lectures. We conclude that TOMO should be delivered by using various teaching styles rather than focusing on a single method while providing more demonstrations. Teaching tooth morphology to the new generation type of learners efficiently will affect the clinical work of dental graduates.


Treatment of mucocutaneous herpes simplex infections with acyclovir.
Topical acyclovir speeds healing and decreases viral shedding and pain in immunocompromised patients with chronic, ulcerative herpetic lesions; it may be used when one does not wish to add another systemic drug. In severe first-episode and life-threatening infections, acyclovir may be administered intravenously for 7 to 10 days. In milder and non-life-threatening first-episode infections, acyclovir may be given orally in a dosage of 200 mg five times a day for 10 days. With these doses, healing is 50% faster and viral shedding stops 90% sooner. Acyclovir given early during first-episode infections, especially true primary infections, may decrease immune responses to the virus, but these usually become normal later. Fewer than six recurrences a year may be managed by 200 mg acyclovir orally five times a day for 5 days beginning as soon as symptoms appear. More than six recurrences a year, often every month, may be managed by continuous suppressive oral acyclovir therapy. Kaposi's varicelliform eruption responds to acyclovir given orally or intravenously depending on circumstances. Primary and recurrent herpetic whitlow respond to acyclovir.


Use of a Retrograde Guidewire to Direct an Antegrade Femoral Nail.
Antegrade intramedullary nailing for the treatment of diaphyseal femur fractures may present challenges in obtaining appropriate positioning of the distal tip of the nail. Known mismatch between the radius of curvature of commonly used nails and the anatomic bow of the femur may result in impingement or perforation of the anterior cortex of the distal femur. Additionally, some unique scenarios may arise that complicate traditional antegrade wire passage. We report our surgical technique and clinical experience using a retrograde guidewire to direct an antegrade femoral nail to aid in obtaining a desired central location of the distal nail tip. [Orthopedics. 2023;46(2):e132-e135.].


Transitions Between Preexposure Prophylaxis Eligibility States and HIV Infection in the Lisbon Cohort of HIV-Negative Men Who Have Sex With Men: A Multistate Model Analysis.
We aimed to describe transitions between preexposure prophylaxis (PrEP) eligibility and human immunodeficiency virus (HIV) infection among HIV-negative men who have sex with men (MSM). We used data from 1,885 MSM, who had not used PrEP, enrolled in the Lisbon Cohort of MSM, with at least 2 consecutive measurements of PrEP eligibility from 2014-2020. A time-homogeneous Markov multistate model was applied to describe the transitions between states of PrEP eligibility-eligible and ineligible-and from these to HIV infection (HIV). The intensities of the transitions were closer for ineligible-to-eligible and eligible-to-ineligible transitions (intensity ratio, 1.107, 95% confidence interval (CI): 1.080, 1.176), while the intensity of the eligible-to-HIV transition was higher than that for ineligible-to-HIV transition (intensity ratio, 9.558, 95% CI: 0.738, 65.048). The probabilities of transitions increased with time; for 90 days, the probabilities were similar for the ineligible-to-eligible and eligible-to-ineligible transitions (0.285 (95% CI: 0.252, 0.319) vs. 0.258 (95% CI: 0.228, 0.287)), while the eligible-to-HIV transition was more likely than ineligible-to-HIV (0.004 (95% CI: 0.003, 0.007) vs. 0.001 (95% CI: 0.001, 0.008)) but tended to become closer with time. Being classified as ineligible was a short-term indicator of a lower probability of acquiring HIV. Once an individual moved to eligible, he was at a higher risk of seroconversion, demanding a timely delivery ofPrEP.


Binocular correlates of the direction of motion in depth.
Two binocular cues to the direction of an object's motion in depth are the ratio (phi R/phi L) between the velocities of the object's retinal images in the right and left eyes and the ratio (phi/gamma) between the velocity of the binocularly-fused image of the object and the rate of change of disparity. We report that the apparent direction of motion in depth of a monocularly-camouflaged target can be varied by altering the ratio phi/gamma. Because no monocular motion signal is available in this case, we conclude that the ratio phi/gamma is a sufficient cue to the direction of motion in depth. This is not to deny that the phi R/phi L cue might be used in the everyday visual situation where monocular velocities phi R and phi L are available to the brain.


Cardiac assist devices.
During the latter half of the twentieth century, physicians have had the capability to support the circulation with mechanical devices. This article gives an historical overview of those devices. Various devices and their complications are described and evaluated. Patient selection and clinical results also are discussed.


A novel ECG parameter for diagnosis of acute pulmonary embolism: RS time: RS time in acute pulmonary embolism.
Pulmonary embolism (PE) is one of the leading causes of cardiovascular mortality worldwide. Electrocardiography (ECG) may provide useful information for patients with acute PE. In this study, we aimed to investigate the diagnostic value of the QRS duration and RS time in inferolateral leads in patients admitted to the emergency department, and pre-diagnosed with acute PE. We retrospectively enrolled 136 consecutive patients, admitted to the emergency department, pre-diagnosed with the clinical suspicion of acute PE, and underwent computerized tomographic pulmonary angiography (CTPA) to confirm the PE diagnosis. The study subjects were divided into two groups according to the presence or absence of PE, and the independent predictors of PE were investigated. Sixty-eight patients (50%) had PE. Patients with PE had a longer RS time. Among the ECG parameters, only RS time was an independent predictor of PE (OR: 1.397, 95% CI: 1.171-1.667; p < 0.001). The ROC curve analyses revealed that the cut-off value of RS time for predicting acute PE was 64.20 ms with a sensitivity of 85.3% and a specificity of 79.4% (AUC: 0.846, 95%CI: 0.749-0.944; p < 0.001). In the correlation analyses; the RS time was correlated with RV end-diastolic diameter (r = 0.422; p < 0.001), RV/left ventricle (LV) ratio (r = 0.622; p < 0.001), and systolic pulmonary artery pressure (SPAP) (r = 0.508; p < 0.001). As a novel ECG parameter, RS time could be measured for each patient. A longer RS time can be a very useful index for diagnosing acute PE as well as for estimating the RV end-diastolic diameter and SPAP.


[Pneumatosis cystoides intestinalis complicating paraneoplastic dermatomyositis].
Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by the presence of gas-filled cysts within the wall of the digestive tract. Classically, it occurs in lung or colon diseases but rarely in patients with collagen disorders. We report a new case of PCI occurring during the course of paraneoplastic dermatomyositis. A 53-year-old woman was diagnosed with dermatomyositis two years ago. Relapse of dermatomyositis preceded the discovery of metastases for which chemotherapy was initiated with 5-fluorouracil and vinorelbine. Three months later, she was admitted to our department for abdominal pains. On physical examination, the abdomen was distended with normal peristalsis. There was no evidence in favour of active dermatomyositis. Abdominal computed tomography scan showed gas collection in the mesentery, revealing the PCI. There was also pneumoperitoneum. The patient slowly improved with symptomatic treatment. PCI is uncommon in systemic diseases and extremely rare in dermatomyositis. The pathogenesis and aetiology of PCI are unknown in most cases. In collagen diseases, several hypotheses have been suggested: digestive hypokinesia, corticosteroid-induced ulceration and intestinal vasculitis. In our patient, two factors contributed to PCI: corticosteroid administration and a chemotherapeutic agent (vinorelbine), resulting in severe constipation. Diagnosis of PCI is based on abdominal computed tomography. Pneumoperitonitis is frequent. Although rare, the diagnosis of PCI must be evoked in collagen disorder patients presenting nonspecific abdominal symptoms.


Imaging findings in noncraniofacial childhood rhabdomyosarcoma.
Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood. This paper is focuses on imaging for diagnosis, staging, and follow-up of noncraniofacial RMS.


Determination of serum ionised calcium by ion-exchange electrode in normal subjects.
Serum ionised calcium concentration [Ca2+] was measured with a calcium selective electrode in 65 normal people. A mean value of 1.06 mmol/l (+/- 0.04 S.D.) with an actual range of 0.97 to 1.13 mmol/l was obtained. Serum samples refrigerated at 4 degrees C for 24 h were satisfactory for analysis. Storage of whole blood samples for 6 h at room temperature before separation caused a very small error (+0.04 mmol/l). Mean results and ranges were similar in males and females and there was no significant correlation with age. No significant change in serum [Ca2+] was found following a normal meal. Serum [Ca2+] and total serum calcium showed a very slight correlation (r = 0.35). The method is reproducible and sensitive.


Selective attention deficits in early and moderate stage Parkinson's disease.
Patients with Parkinson's disease (PD) often show impaired performance on visuospatial attentional tasks. The objective of the study was to examine the attentional function of PD patients performing the attentional network test (ANT). We used the ANT to compare PD patients with healthy controls with respect to the efficiency of 3 anatomically defined attentional networks: the alerting, orienting, and executive control networks. We found that PD patients showed a selective abnormality in the orienting network. Although the alerting and executive control networks apparently remained unaffected, the efficiencies of these networks in patients with PD negatively correlated with the Hoehn-Yahr stage. The results supported the idea that the orienting processes may be more dynamic in PD than in non-PD individuals.


A Community "Hub" Network Intervention for HIV Stigma Reduction: A Case Study.
We describe the implementation of a community "hub" network intervention to reduce HIV stigma in the Tlokwe Municipality, North West Province, South Africa. A holistic case study design was used, focusing on community members with no differentiation by HIV status. Participants were recruited through accessibility sampling. Data analyses used open coding and document analysis. Findings showed that the HIV stigma-reduction community hub network intervention successfully activated mobilizers to initiate change; lessened the stigma experience for people living with HIV; and addressed HIV stigma in a whole community using a combination of strategies including individual and interpersonal levels, social networks, and the public. Further research is recommended to replicate and enhance the intervention. In particular, the hub network system should be extended, the intervention period should be longer, there should be a stronger support system for mobilizers, and the multiple strategy approach should be continued on individual and social levels.