The effect of nutrition training for health care staff on learner and patient outcomes in adults: a systematic review and meta-analysis.
Background: Nutrition training for health care staff has been prioritized internationally as a key means of tackling malnutrition; however, there is a lack of clear evidence to support its implementation. Systematic reviews in other fields of training for health care staff indicate that training strategies may have a beneficial impact on learner and patient outcomes.Objectives: We assessed whether nutrition training for health care staff caring for nutritionally vulnerable adults resulted in improved learner and patient outcomes and evaluated the effectiveness of different training strategies.Design: A systematic review of trials of nutrition training for health care staff was conducted. Six databases were searched with key terms relating to malnutrition and nutrition training. Studies were categorized according to cognitive (didactic teaching), behavioral (practical implementation of skills), and psychological (individualized or group feedback and reflection) training strategies. Where sufficient data were available, meta-analysis was performed according to study design and training strategy. All study designs were eligible. The risk of bias was evaluated in accordance with Cochrane guidance.Results: Twenty-four studies met the eligibility criteria: 1 randomized controlled trial, 4 nonrandomized controlled trials, 3 quasi-experimental trials, 13 longitudinal pre-post trials, 2 qualitative studies, and 1 cross-sectional survey. Results from a number of low-quality studies suggest that nutrition training for health care staff may have a beneficial effect on staff nutrition knowledge, practice, and attitude as well as patient nutritional intake. There were insufficient data to determine whether any particular training strategy was more effective than the others.Conclusions: In the absence of high-quality evidence, low-quality studies suggest that nutrition training for health care staff has some positive effects. However, further randomized controlled trials are required to confirm overall efficacy and to explore the impact of training strategies on learner and patient outcomes.


Lateral Ge Diffusion During Oxidation of Si/SiGe Fins.
This Letter reports on the unusual diffusion behavior of Ge during oxidation of a multilayer Si/SiGe fin. It is observed that oxidation surprisingly results in the formation of vertically stacked Si nanowires encapsulated in defect free epitaxial strained SixGe1-x. High angle annular dark field scanning transmission electron microscopy (HAADF-STEM) shows that extremely enhanced diffusion of Ge occurs along the vertical Si/SiO2 oxidizing interface and is responsible for the encapsulation process. Further oxidation fully encapsulates the Si layers in defect free single crystal SixGe1-x (x up to 0.53), which results in Si nanowires with up to -2% strain. Atom probe tomography reconstructions demonstrate that the resultant nanowires run the length of the fin. We found that the oxidation temperature plays a significant role in the formation of the Si nanowires. In the process range of 800-900 °C, pure strained and rounded Si nanowires down to 2 nm in diameter can be fabricated. At lower temperatures, the Ge diffusion along the oxidizing Si/SiO2 interface is slow, and rounding of the nanowire does not occur, while at higher temperatures, the diffusivity of Ge into Si is sufficient to result in dilution of the pure Si nanowire with Ge. The use of highly selective etchants to remove the SiGe could provide a new pathway for the creation of highly controlled vertically stacked nanowires for gate all around transistors.


Effectiveness of selected chemicals for controlling emission of malodorous sulfur gases in sewage sludge.
The effectiveness of various oxidants or redox buffers (ferric chloride, sodium hypochlorite, potassium permanganate, hydrogen peroxide and potassium nitrate) for controlling or reducing emission of reduced sulfur gases (hydrogen sulfide, carbonyl sulfide, methanethiol, dimethyl sulfide and carbon disulfide) produced from sewage sludge collected from a wastewater treatment plant was studied under laboratory conditions. Sludge was treated with 0, 30, 300 and 1000 ppm of each chemical and changes in emission of the various reduced sulfur gases were monitored over a period of 24 hours. Potassium permanganate and hydrogen peroxide were shown to be the best chemicals for reducing hydrogen sulfide (the dominant reduced sulfur gas measured) emission. Sodium hypochlorite was also effective in reducing hydrogen sulfide emission followed by the ferric chloride addition. Since considerably smaller quantities of other reduced sulfur gases were evolved, the influence of the various chemical additions were not as significant as the reduction observed for hydrogen sulfide emission. Potassium permanganate and hydrogen peroxide were effective in reducing methanethiol and dimethyl sulfide emission. To a lesser degree sodium hypochlorite and ferric chloride also reduced emission of these two reduced sulfur gases. Potassium nitrate had no effect on reducing hydrogen sulfide or any of the reduced sulfur gases over the 24 hour experimental period. Each of the chemicals used in the study had a little or no effect in reducing carbonyl sulfide and carbon disulfide emission from the sludge material.


Patients may respond differently to paper and electronic versions of the same questionnaires.
To adapt the Asthma Quality of Life Questionnaire (AQLQ(S)), the Asthma Control Questionnaire (ACQ) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)) for a personal digital assistant (Palm TX) and to examine the validity of the electronic versions by comparing them with the original paper versions. 84 adults with asthma and 32 with rhinitis were randomised to complete either the paper or the electronic version first. After 2h, they completed the other version. 68 asthma and 27 rhinitis patients provided analysable data. For the AQLQ(S) and RQLQ(S) differences between paper and electronic were significant. Concordance between paper and electronic, evaluated using an intraclass correlation coefficient were: AQLQ=0.92, ACQ=0.90 and RQLQ=0.85. Concordance for the individual domains of the AQLQ and RQLQ ranged from 0.52 to 0.94. These levels of concordance did not reach the a priori defined requirement for validity. The significant bias between paper and electronic versions and only modest concordance provides evidence that patients may respond differently to questionnaires in different formats and show that different formats must not be used interchangeably.


Serum antibodies to the major proteins found in cow's milk of Iranian patients with Type 1 diabetes mellitus.
The purpose of this study was to assess the humoral immune response to cow's milk proteins in Iranian children with Type 1 diabetes mellitus (T1DM). Eighty children aged 4-17 yr with T1DM from two centres in Iran (the Iranian Association of Diabetes in Tehran and Center for Diabetes Research in Hamedan), 37 apparently healthy siblings of diabetic patients (related controls), 82 apparently healthy age- and sex- matched controls (unrelated controls), and 32 patients aged 11-15 yr with auto-immune thyroiditis were examined for specific whole antibodies (Igs), IgG, and IgM to the major proteins found in cow's milk or to ovo-albumin by enzyme-linked immunosorbent assay (ELISA). A crude extract was made from 2.5% fat pasteurized cow's milk. This extract, together with individual commercial major proteins of cow's milk, was then used as antigen to evaluate the humoral immune response of the subjects to the individual proteins found in cow's milk or to cow's milk as a whole. A questionnaire on medical history, duration of exclusive and non-exclusive breast-feeding and daily intake of dairy products was completed before blood sampling. Diabetic children had significantly higher serum levels of Igs, IgG and IgM to the proteins found in cow's milk than unrelated healthy controls (p<0.001). Healthy siblings of diabetic patients, compared to unrelated controls, had significantly higher levels of serum Igs and IgG to cow's milk proteins (p<0.05 and p<0.01, respectively). Serum levels of Igs and IgG to the cow's milk proteins showed a significantly negative correlation with duration of non-exclusive breast-feeding but positive correlation with daily intake of dairy products. These correlations were stronger when calculated just within the T1DM group. In this group, serum levels of IgM to cow's milk proteins also showed a positive correlation with daily intake of dairy products. Though serum levels of IgG to casein were insignificantly higher in diabetic children than in healthy controls, there was a significant negative correlation between serum levels of IgG to casein and duration of non-exclusive breast-feeding. Again in the T1DM group, this correlation was stronger. There was no significant difference in serum levels of Igs, IgG or IgM to other major proteins of cow's milk or to ovo-albumin between groups. It was concluded that though high levels of Igs or IgG were found to cow's milk proteins, especially casein, it seems unrelated to the early introduction of cow's milk into an infant diet and the onset of T1DM in Iranian subjects.


[Massive bilateral non-Hodgkin's lymphoma of the adrenal glands].
The patient was a 47-year-old male who attended our hospital complaining of back pain. Masses in the bilateral adrenal glands were noted on abdominal ultrasonography and the patient was admitted to the hospital on August 9, 1988. Upon test laparotomy, non-Hodgkin's lymphoma (diffuse small-cell type, B-cell type) was diagnosed, and endocrinological examination revealed hypofunction of the adrenal gland. The results of various tests showed absence of distance metastasis except for that to the bilateral adrenal glands. Since complete remission was attained after 2 courses of COP-BLAM III therapy, and adrenal function also became normal, the patient was discharged on January 9, 1989. Malignant lymphoma originating from the adrenal gland seems to be a rare condition, and only 16 cases have been reported to this date.


Oestrogen action on the myocardium in vivo: specific and permissive for angiotensin-converting enzyme inhibition.
In contrast to the vasculature, it remains unclear whether oestrogens also directly affect the myocardium. In this study, we addressed basic questions regarding oestrogen effects on the myocardium, including specificity, pathophysiological relevance and potential clinical implications, with a special focus on interactions between oestrogen and angiotensin-converting enzyme (ACE) inhibitors in an established in-vivo model of cardiac hypertrophy. Female spontaneously hypertensive rats (SHR) were ovarectomized (OVX) or sham-operated and treated with 17beta-oestradiol (2 microg/kg per day subcutaneously), the oestrogen receptor antagonist ZM-182780 (250 microg/kg per day subcutaneously) and the ACE-inhibitor moexipril (10 mg/kg per day orally) alone or in combination for 3 months. Hormone replacement restored physiological oestradiol serum levels and prevented uterus atrophy. Whereas moexipril alone was ineffective in OVX rats, substitution of oestradiol restored the beneficial effect of moexipril on systolic blood pressure (-30 +/- 5 mmHg) and relative heart weight (-11 +/- 3%) in OVX rats. Oestradiol upregulated alpha-myosin heavy chain (MHC) mRNA (+37 +/- 7%) and protein expression (+43 +/- 6%) in spite of increased blood pressure in OVX rats. Simultaneous treatment with oestradiol plus moexipril most effectively shifted the ratio of alpha-/beta-MHC mRNA and protein expression towards alpha-MHC in OVX animals. Oestradiol (10 nmol/l) also upregulated alpha-MHC mRNA and protein in cultured cardiac myocytes. The oestrogen receptor antagonist ZM-182780 significantly inhibited the observed oestrogen effects. Oestrogen replacement is permissive for the beneficial effects of ACE-inhibition in female SHR rats. Oestrogen effects on the myocardium in vivo are specific (i.e. oestrogen receptor mediated) because they are inhibited by a pure oestrogen receptor antagonist and occur at physiological hormone levels.


Collagenous colitis in an adult patient with chronic diarrhoea: case report.
Collagenous colitis is an established cause of chronic watery diarrhoea of unknown aetiopathogenesis, characterised by normal colonic endoscopic findings, and a prominent collagen band in the sub-epithelial layer on colonic mucosal histology. We report a case of a 65-year old male who presented with recurrent episodes of watery diarrhoea of 38 years duration. There was a positive family history of similar diarrhoea in the mother and two siblings. Colonoscopy done was macroscopically unremarkable except for a redundant sigmoid colon. Mucosal biopsy of the rectum and colon showed at histology atrophy of the mucosal lining, infiltration of the lamina propria by plasma cells and lymphocytes, and a thick band of collagenous tissue in the sub-epithelial zone of the lining mucosa. A high index of suspicion is necessary to make the diagnosis in patients with chronic diarrhoea, especially when common causes of chronic diarrhoea like intestinal parasitoses, HIV/AIDS, diabetic autonomic neuropathy, thyrotoxicosis have been excluded. It is suggested that colonoscopic examination with adequate biopsy should be performed in patients with chronic diarrhoea with no aetiologic agent identified.


Helicobacter pylori antibiotic resistance patterns and genotypes in adult dyspeptic patients from a regional population in North Wales.
Surveillance data on Helicobacter pylori antibiotic susceptibilities in Wales are limited, despite resistance being a key factor in treatment failure. A single-centre survey was undertaken over 3 years to determine local antibiotic resistance rates on isolates from dyspeptic patients in Bangor, Gwynedd (North Wales). Susceptibilities were determined for 363 isolates by disc diffusion and the Etest. Isolates were also genotyped (cagA presence and vacA allelic types). Overall in vitro resistance rates were 24% for metronidazole and 7% for clarithromycin, with 4% resistant to both antibiotics. Resistant strains typically had high MICs of >256 mg/L. Tetracycline resistance was identified in only one isolate whereas no isolates showed resistance to amoxicillin. There was a two-fold increase in resistance over the study period. No gender and age associations with resistance were detected. Resistant and susceptible isolates were genotypically diverse with respect to cagA/vacA type but the vacA s1m2 form was a feature of all clarithromycin-resistant isolates compared with 56% of the susceptible isolates. Although the overall antibiotic resistance rates of H. pylori from North Wales were low compared with many other regions in Europe, continued surveillance, particularly of high-level resistance (MIC >256 mg/L), is recommended to monitor the effects of the 'test and treat' strategy for H. pylori eradication.


Taking Advantage of the Teachable Moment: A Review of Learner-Centered Clinical Teaching Models.
When working in a chaotic Emergency Department (ED) with competing priorities, clinical teaching may be sacrificed for the sake of patient flow and throughput. An organized, efficient approach to clinical teaching helps focus teaching on what the learner needs at that moment, incorporates regular feedback, keeps the department on track, and prevents over-teaching. Effective clinical teaching in a busy environment is an important skill for senior residents and faculty to develop. This review will provide a critique and comparison of seven structured teaching models to better prepare readers to seize the teachable moment.


Plasma concentrations of catecholamines following adrenaline infiltration during gynaecological surgery.
High pressure liquid chromatography with electrochemical detection has been used to measure plasma catecholamine concentrations in six gynaecological patients undergoing halothane anaesthesia for cervical cone biopsy. Mean catecholamine concentrations before infiltration were 1.01 +/- 0.23 (SEM) nmol litre-1 (185 +/- 43 pg ml-1) for adrenaline, and 2.2 +/- 0.25 nmol litre-1 (364 +/- 41 (185 +/- 43 pg ml-1) for adrenaline, and 2.2 +/- 0.25 nmol litre-1 (364 +/- 41 pg ml-1) for noradrenaline. Following infiltration with 0.5% bupivacaine 15 ml with adrenaline 1:200 000, plasma adrenaline concentrations increased to a mean peak concentration of 18.6 +/- 3.7 nmol litre-1 (3.4 +/- 0.69 ng litre-1). The lack of sympathoneuronal response was confirmed by simultaneous measurements of plasma noradrenaline concentrations, which did not change significantly. The proportion of the injected adrenaline measured in the intravascular compartment was 21.8%. The significance of intravascular absorption of exogenous adrenaline is discussed in relation to the use of halothane anaesthesia and the concurrent injection of a local anaesthetic solution.


FDA to Consider Real-World Evidence.
The FDA released a framework outlining how it plans to incorporate real-world evidence into the drug review process. The agency will consider real-world evidence to support the approval of new indications for approved drugs and to support or satisfy post-approval study requirements.


Medicare Switching: Patterns Of Enrollment Growth In Medicare Advantage, 2006-22.
Medicare Advantage (MA) has grown rapidly over the course of the past two decades and is projected to continue to grow. We examined sources of new enrollment in MA and analyzed the switching patterns between MA and traditional fee-for-service Medicare, using more recent and more detailed data than in previous analyses. We found that switching from fee-for-service Medicare to MA more than tripled between 2006 and 2022, whereas switching from MA to fee-for-service Medicare decreased, with the change rates accelerating since 2019. The share of switchers among all new MA enrollees rose from 61 percent in 2011 to 80 percent in 2022. Black, dual-eligible, and disabled beneficiaries had higher odds of switching in both directions, whereas younger and healthier beneficiaries had higher odds of switching from fee-for-service Medicare to MA but lower odds of switching from MA to fee-for-service Medicare. Two-thirds of annual switching between MA and fee-for-service Medicare in 2022 occurred in January, likely reflecting the open enrollment period.


Chromatofocusing purification of CD1b-antigen complexes and their analysis by isoelectric focusing.
The presentation of lipid antigens to T cells is mediated by the CD1 proteins. Purified functional CD1/lipid complexes are valuable tools to investigate such immune processes. Here, we describe how these complexes can be prepared in vitro, how they can be purified by chromatofocusing and how to control their antigen-loading status by isoelectric focusing.


Metabolism and toxicological analysis of synthetic cannabinoids in biological fluids and tissues.
Synthetic cannabinoids, which began proliferating in the United States in 2009, have gone through numerous iterations of modification to their chemical structures. More recent generations of compounds have been associated with significant adverse outcomes following use, including cognitive and psychomotor impairment, seizures, psychosis, tissue injury and death. These effects increase the urgency for forensic and public health laboratories to develop methods for the detection and identification of novel substances, and apply these to the determination of their metabolism and disposition in biological samples. This comprehensive review describes the history of the appearance of the drugs in the United States, discusses the naming conventions emerging to designate new structures, and describes the most prominent new compounds linked to the adverse effects now associated with their use. We review in depth the metabolic pathways that have been elucidated for the major members of each of the prevalent synthetic cannabinoid drug subclasses, the enzyme systems responsible for their metabolism, and the use of in silico approaches to assist in predicting and identifying the metabolites of novel compounds and drug subclasses that will continue to appear. Finally, we review and critique analytical methods applied to the detection of the drugs and their metabolites, including immunoassay screening, and liquid chromatography mass spectrometry confirmatory techniques applied to urine, serum, whole blood, oral fluid, hair, and tissues.


Transmission of 12 kV Grenz rays and 29 kV X-rays through normal and diseased nails.
Bucky and X-rays are used in the treatment of nailbed diseases. Transmission through normal and diseased nails has been measured. Nails of normal thickness transmit about 30% of Bucky rays and about 85% of X-rays. Bucky rays cannot be used when the diseased nails are thickened, whereas 60% of X-rays are transmitted.


Solid-state fermentation and composting as alternatives to treat hair waste: A life-cycle assessment comparative approach.
One of the wastes associated with leather production in tannery industries is the hair residue generated during the dehairing process. Hair wastes are mainly dumped or managed through composting but recent studies propose the treatment of hair wastes through solid-state fermentation (SSF) to obtain proteases and compost. These enzymes are suitable for its use in an enzymatic dehairing process, as an alternative to the current chemical dehairing process. In the present work, two different scenarios for the valorization of the hair waste are proposed and assessed by means of life-cycle assessment: composting and SSF for protease production. Detailed data on hair waste composting and on SSF protease production are gathered from previous studies performed by our research group and from a literature survey. Background inventory data are mainly based on Ecoinvent version 3 from software SimaPro® 8. The main aim of this study was to identify which process results in the highest environmental impact. The SSF process was found to have lower environmental impacts than composting, due to the fact that the enzyme use in the dehairing process prevents the use of chemicals traditionally used in the dehairing process. This permits to reformulate an industrial process from the classical approach of waste management to a novel alternative based on circular economy.


The density matrix formalism of nuclear relaxation: a review.
This is a review of the density matrix formalism of quantum statistical mechanics as it relates to nuclear relaxation. The single spin and coupled exchanging two spin systems are treated explicitly. We show the circumstances under which these models reduce to the more familiar expressions used to describe proton relaxation in tissue. The effect of radiofrequency (rf) pulses on the density matrix is presented as well as the density matrix description of the Carr-Purcell pulse technique and conditions under which even and odd echo trains will superpose or are independent of rf pulse rate.


Training in timing improves accuracy in golf.
In this experiment, the authors investigated the influence of training in timing on performance accuracy in golf. During pre- and posttesting, 40 participants hit golf balls with 4 different clubs in a golf course simulator. The dependent measure was the distance in feet that the ball ended from the target. Between the pre- and posttest, participants in the experimental condition received 10 hr of timing training with an instrument that was designed to train participants to tap their hands and feet in synchrony with target sounds. The participants in the control condition read literature about how to improve their golf swing. The results indicated that the participants in the experimental condition significantly improved their accuracy relative to the participants in the control condition, who did not show any improvement. We concluded that training in timing leads to improvement in accuracy, and that our results have implications for training in golf as well as other complex motor activities.


Management of influenza - updated Swedish guidelines for antiviral treatment.
Influenza causes seasonal epidemics of respiratory infection in all parts of the world. Manifestations of influenza range from mild upper to severe lower respiratory tract infection. Medical risk groups are defined by factors predisposing for development of severe disease and are recommended annual vaccination as a protective measure. The previous Swedish treatment guidelines for influenza were issued in 2011, and a review of current evidence was deemed relevant. An important reason to revisit the guidelines is the recent approval of a novel drug for influenza treatment, baloxavir. Updated Swedish evidence-based guidelines created by a group of experts from various research areas, for the management of influenza are presented here. The work has been made in collaboration with the Public Health Agency of Sweden and the Swedish Reference Group for AntiViral therapy (RAV). The updated guidelines include guidelines for diagnostics, treatment and prophylaxis in special groups, including management of pregnant women and children with influenza. A new section about infection control has been added. Pharmacological treatment is covered in detail with regards to indication and dosage. Additionally, drug resistance and environmental aspects are discussed.


A review of ketamine in affective disorders: current evidence of clinical efficacy, limitations of use and pre-clinical evidence on proposed mechanisms of action.
Recent research has seen low-dose ketamine emerge as a novel, rapid-acting antidepressant. Ketamine, an N-methy-d-aspartate (NMDA) receptor antagonist, leads to effects on the glutamatergic system and abnormalities in this neurotransmittor system are present in depression. This article aims to (1) review the clinical literature on low-dose ketamine as a rapid-acting antidepressant in affective disorders, (2) provide a critical overview of the limitations of ketamine and research attempts to overcome these (3) discuss the proposed mechanisms of action of ketamine and (4) point towards future research directions. The electronic database Pubmed, Web of Science and sciencedirect were searched using the keywords: ketamine, N-methyl-d-aspartate receptor antagonist, rapid-acting antidepressant, depression, treatment-resistant depression, bipolar depression, suicidal ideation, electroconvulsive therapy, mechanism of action. The literature demonstrates evidence supporting a rapid-acting antidepressant effect of low-dose intravenous ketamine in major depressive disorder, in bipolar depression and in depression with suicidal ideation. There are mixed results as to whether ketamine leads to a reduction in time to remission in patients undergoing electroconvulsive therapy (ECT). Efforts to unravel ketamine's therapeutic mechanism of action have implicated the mammalian target of rapamycin (mTOR)-dependent synapse formation in the rat prefrontal cortex, eukaryotic elongation factor 2 phosphorylation (p-eEF2) and glycogen synthase kinase (GSK-3). Ketamine's limiting factors are the transient nature of its antidepressant effect and concerns regarding abuse, and research efforts to overcome these are reviewed. Current and future research studies are using ketamine as a promising tool to evaluate the glutamatergic neurotransmittor system to learn more about the pathophysiology of depression and develop more specific rapid-acting antidepressant treatments.


Exploring intellectual humility through the lens of artificial intelligence: Top terms, features and a predictive model.
Intellectual humility (IH) is often conceived as the recognition of, and appropriate response to, your own intellectual limitations. As far as we are aware, only a handful of studies look at interventions to increase IH - e.g. through journalling - and no study so far explores the extent to which having high or low IH can be predicted. This paper uses machine learning and natural language processing techniques to develop a predictive model for IH and identify top terms and features that indicate degrees of IH. We trained our classifier on the dataset from an existing psychological study on IH, where participants were asked to journal their experiences with handling social conflicts over 30 days. We used Logistic Regression (LR) to train a classifier and the Linguistic Inquiry and Word Count (LIWC) dictionaries for feature selection, picking out a range of word categories relevant to interpersonal relationships. Our results show that people who differ on IH do in fact systematically express themselves in different ways, including through expression of emotions (i.e., positive, negative, and specifically anger, anxiety, sadness, as well as the use of swear words), use of pronouns (i.e., first person, second person, and third person) and time orientation (i.e., past, present, and future tenses). We discuss the importance of these findings for IH and the value of using such techniques for similar psychological studies, as well as some ethical concerns and limitations with the use of such semi-automated classifications.


Regulatory mechanism governing the diurnal rhythm of intestinal H+/peptide cotransporter 1 (PEPT1).
The intestinal H(+)/peptide cotransporter 1 (PEPT1) plays important roles as a nutrient and drug transporter. Previously, we reported that rat intestinal PEPT1 showed a diurnal rhythm and that this rhythm is closely related to the feeding schedule. Furthermore, we also demonstrated that transcription factors, Sp1, Cdx2, and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) contribute to the basal, intestine-specific, and fasting-induced expression of PEPT1, respectively. In this study, to clarify the molecular mechanism governing the diurnal rhythm of PEPT1 expression, we compared expression profiles of these transcription factors under two kinds of feeding schedules. The intestinal Sp1 and Cdx2 did not show a circadian accumulation of mRNA or response to the daytime feeding regimen. Plasma free fatty acids, endogenous PPAR-alpha ligands, exhibited a robust circadian fluctuation in phase with that of PEPT1. However, subsequent experiments using PPAR-alpha-null mice revealed the absence of any association between the circadian rhythm of PEPT1 and PPAR-alpha. We then focused on the clock genes (Clock, Bmal1, Per1-2, and Cry1) and clock-controlled gene, albumin D site-binding protein (DBP). A robust and coordinated circadian expression of the clock genes was observed, and daytime feeding entirely inverted the phase except for Clock. The expression of DBP was in phase with that of PEPT1 in both groups. Electrophoretic mobility shift assays and reporter assays revealed that DBP has the ability to bind the DBP binding site located in the distal promoter region of the rat PEPT1 gene and induce the transcriptional activity. These findings indicate that DBP plays pivotal roles in the circadian oscillation of PEPT1.


Modeling bisubstrate removal by biofilms.
A bisubstrate secondary utilization model is based on the concept that an individual substrate can be utilized not only by the biomass by its utilization but also by the biomass made from the utilization of the other substrate. When substrate concentrations are low, a key factor is having sufficient substrate to initiate biofilm growth. Modeling results for three characteristic cases demonstrate that satisfying a total S(min) concentration for a bisubstrate system is the necessary condition for initiating biofilm growth and simultaneous utilization of both substrates. Because having more than one substrate supporting biofilm growth enhances the removal of each compound, the utilization rate of a specific compound can be increased by the concentration of other compounds, and the total S(min) concentration can be less than the weighted average of individual S(min) values.


Folding and assembly of phage P22 tailspike endorhamnosidase lacking the N-terminal, head-binding domain.
Tryptic digestion of a thermal unfolding intermediate of the phage P22 tailspike endorhamnosidase produces an N-terminally shortened protein fragment comprising amino-acid residues 108-666 [Chen, B.-L. & King, J. (1991) Biochemistry 30, 6260-6269]. In the present work, the 60-kDa C-terminal fragment was purified to homogeneity from the tryptic digest by gel-fitration chromatography. As in the case for the whole tailspike protein (72 kDa), the purified fragment was found to remain stably folded as a highly soluble, SDS-resistant, enzymatically active trimer. However, its unfolding in the presence of guanidinium chloride was accelerated at least 10-fold compared to the complete, native tailspike protein. Shortened tailspike trimers reconstituted spontaneously and with high yield after diluting a solution containing acid-urea-unfolded fragment polypeptides with neutral buffer. Upon recombinant expression of the 60-kDa polypeptide in Escherichia coli, it also assembled efficiently and formed SDS-resistant trimers. The refolding and assembly pathway of the N-terminally shortened tailspike paralleled that of the complete protein with slightly, but significantly, accelerated folding reactions, at both the subunit and the trimer levels. As found for the complete tailspike protein, yields of refolding and assembly of the 60-kDa fragments into SDS-resistant trimers decreased with increasing temperature. The refolding yield of fragments derived from a temperature-sensitive mutant (Gly244-->Arg) tailspike protein was affected in similar fashion as shown for the whole protein. We conclude that the N-terminal domain (residues 1-107) is dispensable for folding and assembly of the P22 tailspike endorhamnosidase both in vitro and in vivo.


Intraperitoneally Delivered Mesenchymal Stem Cells Alleviate Experimental Colitis Through THBS1-Mediated Induction of IL-10-Competent Regulatory B Cells.
Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating inflammatory bowel disease (IBD), and intraperitoneal delivery of MSCs have become a more effective route for IBD treatment. However, the underlying mechanisms are still poorly understood. Here, we found that intraperitoneally delivered MSCs significantly alleviated experimental colitis. Depletion of peritoneal B cells, but not macrophages, clearly impaired the therapeutic effects of MSCs. Intraperitoneally delivered MSCs improved IBD likely by boosting the IL-10-producing B cells in the peritoneal cavity, and a single intraperitoneal injection of MSCs could significantly prevent disease severity in a recurrent mouse colitis model, with lower proinflammation cytokines and high level of IL-10. The gene expression profile revealed that thrombospondin-1 (THBS1) was dramatically upregulated in MSCs after coculture with peritoneal lavage fluid from colitis mice. Knockout of THBS1 expression in MSCs abolished their therapeutic effects in colitis and the induction of IL-10-producing B cells. Mechanistically, THBS1 modulates the activation of transforming growth factor-β (TGF-β), which combines with TGF-β receptors on B cells and contributes to IL-10 production. Blocking the interaction between THBS1 and latent TGF-β or inhibiting TGF-β receptors (TGF-βR) significantly reversed the THBS1-mediated induction of IL-10-producing B cells and the therapeutic effects on colitis. Collectively, our study revealed that intraperitoneally delivered MSCs secreted THBS1 to boost IL-10+Bregs and control the progression and recurrence of colitis, providing new insight for the prevention and treatment of IBD.


Multivariate models of adult Pacific salmon returns.
Most modeling and statistical approaches encourage simplicity, yet ecological processes are often complex, as they are influenced by numerous dynamic environmental and biological factors. Pacific salmon abundance has been highly variable over the last few decades and most forecasting models have proven inadequate, primarily because of a lack of understanding of the processes affecting variability in survival. Better methods and data for predicting the abundance of returning adults are therefore required to effectively manage the species. We combined 31 distinct indicators of the marine environment collected over an 11-year period into a multivariate analysis to summarize and predict adult spring Chinook salmon returns to the Columbia River in 2012. In addition to forecasts, this tool quantifies the strength of the relationship between various ecological indicators and salmon returns, allowing interpretation of ecosystem processes. The relative importance of indicators varied, but a few trends emerged. Adult returns of spring Chinook salmon were best described using indicators of bottom-up ecological processes such as composition and abundance of zooplankton and fish prey as well as measures of individual fish, such as growth and condition. Local indicators of temperature or coastal upwelling did not contribute as much as large-scale indicators of temperature variability, matching the spatial scale over which salmon spend the majority of their ocean residence. Results suggest that effective management of Pacific salmon requires multiple types of data and that no single indicator can represent the complex early-ocean ecology of salmon.


Evidence for kappa 1 opioid receptor multiplicity in the guinea pig cerebellum.
Both [3H]U69,593 alone and [3H]ethylketocyclazocine (EKC) in the presence of mu and delta blockers ([D-Ala2,MePhe4,Glyol5]enkephalin (DAMGO) and [D-Pen2,D-Pen5]enkephalin (DPDPE)) label kappa receptors in the guinea pig cerebellum. Dynorphin A(1-17) and nor-binaltorphimine (nor-BNI) potently competed the binding of both radioligands with Hill coefficients of approximately unity, strongly supporting a kappa classification of binding. However, saturation studies revealed that the Bmax for [3H]EKC binding was 45% greater than that for [3H]U69593, suggesting that [3H]EKC might be labeling more than one site. Although nonlinear regression analysis of dynorphin A(1-17) and nor-BNI competition of [3H]EKC binding best fit the curves with a one site model, competitions by dynorphin B, dynorphin A(1-9) and alpha-neoendorphin revealed Hill coefficients less than unity and were best fit to a two site model. Kinetic analysis also supported [3H]EKC binding heterogeneity. Together, these studies imply that under these conditions [3H]EKC labels more than one site in the guinea pig cerebellum. The sensitivity of all specific [3H]EKC binding to the selective kappa ligands dynorphin A(1-17) and nor-BNI indicates that both component are kappa while the differing sensitivities of dynorphin B, alpha-neoendorphin and dynorphin A(1-9) for these components support our previous hypothesis of kappa 1a and kappa 1b binding subtypes.


Improved Pixel-Level Pavement-Defect Segmentation Using a Deep Autoencoder.
Convolutional neural networks perform impressively in complicated computer-vision image-segmentation tasks. Vision-based systems surpass humans in speed and accuracy in quality inspection tasks. Moreover, the maintenance of big infrastructures, such as roads, bridges, or buildings, is tedious and time-demanding work. In this research, we addressed pavement-quality evaluation by pixelwise defect segmentation using a U-Net deep autoencoder. Additionally, to the original neural network architecture, we utilized residual connections, atrous spatial pyramid pooling with parallel and "Waterfall" connections, and attention gates to perform better defect extraction. The proposed neural network configurations showed a segmentation performance improvement over U-Net with no significant computational overhead. Statistical and visual performance evaluation was taken into consideration for the model comparison. Experiments were conducted on CrackForest, Crack500, GAPs384, and mixed datasets.


Candidate genes for obstructive sleep apnea in non-syndromic children with craniofacial dysmorphisms - a narrative review.
Pediatric obstructive sleep apnea (POSA) is a complex disease with multifactorial etiopathogenesis. The presence of craniofacial dysmorphisms influencing the patency of the upper airway is considered a risk factor for POSA development. The craniofacial features associated with sleep-related breathing disorders (SRBD) - craniosynostosis, retrognathia and micrognathia, midface and maxillary hypoplasia - have high heritability and, in a less severe form, could be also found in non-syndromic children suffering from POSA. As genetic factors play a role in both POSA and craniofacial dysmorphisms, we hypothesize that some genes associated with specific craniofacial features that are involved in the development of the orofacial area may be also considered candidate genes for POSA. The genetic background of POSA in children is less explored than in adults; so far, only one genome-wide association study for POSA has been conducted; however, children with craniofacial disorders were excluded from that study. In this narrative review, we discuss syndromes that are commonly associated with severe craniofacial dysmorphisms and a high prevalence of sleep-related breathing disorders (SRBD), including POSA. We also summarized information about their genetic background and based on this, proposed 30 candidate genes for POSA affecting craniofacial development that may play a role in children with syndromes, and identified seven of these genes that were previously associated with craniofacial features risky for POSA development in non-syndromic children. The evidence-based approach supports the proposition that variants of these candidate genes could lead to POSA phenotype even in these children, and, thus, should be considered in future research in the general pediatric population.


Selective Epitaxial Growth of Ca2NH and CaNH Thin Films by Reactive Magnetron Sputtering under Hydrogen Partial Pressure Control.
Calcium compounds with N and H are promising catalysts for NH3 conversion, and their epitaxial thin films provide a platform to quantitatively understand the catalytic activities. Here we report the selective epitaxial growth of Ca2NH and CaNH thin films by controlling the hydrogen partial pressure (PH2) during reactive magnetron sputtering. We find that the hydrogen charge states can be tuned by PH2: Ca2NH containing H- is formed at PH2 < 0.04 Pa, while CaNH containing H+ is formed at PH2 > 0.04 Pa. In situ plasma emission spectroscopy reveals that the intensity of the Ca atomic emission (∼422 nm) decreases as PH2 increases, suggesting that Ca reacts with H2 and N2 to form Ca2NH at lower PH2, whereas at higher PH2, CaHx is first formed on the target surface and then sputtered to produce CaNH. This study provides a novel route to control the hydrogen charge states in Ca-N-H epitaxial thin films.


Successful Treatment of Placental Chorangiomas by Ultrasound-Guided Percutaneous in utero Microcoil Embolization.
Placental chorangiomas can cause a high-output fetal state and increase neonatal morbidity and mortality. There is a paucity of data published describing the optimal treatment of these cases, and methods for occlusion to date include placement of vascular clips, bipolar cautery, injection of alcohol or surgical glue, interstitial laser, and microcoil embolization. We report 2 cases of prenatally diagnosed chorangiomas that caused a high-output fetal state and were successfully treated with microcoil embolization. This case series describes our technique and supports microcoil embolization as a potentially safe and effective antenatal treatment option in symptomatic chorangiomas.


Half-dose fingolimod for treating relapsing-remitting multiple sclerosis: Observational study.
To investigate the efficacy and safety of fingolimod (FTY) 0.5 mg administered every other day (FTY-EOD) compared to every day (FTY-ED) in multiple sclerosis patients. Multicentre retrospective observational study. Clinical, laboratory and neuroimaging data were consecutively collected from 60 FTY-EOD and 63 FTY-ED patients. Baseline characteristics were compared using logistic regression. Efficacy in preventing occurrence of relapses and demyelinating lesions was tested using propensity score-adjusted Cox and linear regressions. Weight was inversely associated with risk of switch to FTY-EOD because of any reason (odds ratio (OR) = 0.94, 95% confidence interval (95% CI) = 0.89-0.99, p = 0.026), and female sex and lower baseline lymphocyte count were positively associated with switch because of lymphopenia. Compared to FTY-ED patients, FTY-EOD patients were at higher risk of developing relapses (hazard ratio (HR) = 2.98, 95% CI = 1.07-8.27, p = 0.036) and either relapses or new magnetic resonance imaging (MRI) demyelinating lesions (combined outcome, HR = 2.07, 95% CI = 1.06-4.08, p = 0.034). Within FTY-EOD, treatment with natalizumab before FTY and lower age were positively associated with risk of developing relapses and combined outcome, respectively (HR = 25.71, 95% CI = 3.03-217.57, p = 0.002 and HR = 0.85, 95% CI = 0.77-0.96, p = 0.005). FTY-EOD was overall well tolerated. Disease reactivation was observed in a significant proportion of patients treated with FTY-EOD. Neurologists should be cautious when reducing FTY administration to every other day, especially in younger patients and those previously treated with natalizumab.


Inferences about which of J dependent groups has the largest robust measure of location.
Recently, a multiple comparisons procedure was derived with the goal of determining whether it is reasonable to make a decision about which of J independent groups has the largest robust measure of location. This was done by testing hypotheses aimed at comparing the group with the largest estimate to the remaining J - 1 groups. It was demonstrated that for the goal of controlling the familywise error rate, meaning the probability of one or more Type I errors, well-known improvements on the Bonferroni method can perform poorly. A technique for dealing with this issue was suggested and found to perform well in simulations. However, when dealing with dependent groups, the method is unsatisfactory. This note suggests an alternative method that is designed for dependent groups.


Angiographic study of mutant tissue-type plasminogen activator versus urokinase for acute myocardial infarction.
The effects and problems of intravenous thrombolytic therapy with a bolus injection of mutant tissue plasminogen activator (t-PA) were investigated in 34 patients with first acute myocardial infarction (AMI). In contrast, 114 patients were selected from 1,003 patients with AMI for treatment using intravenous infusion urokinase (UK). Angiography of these 148 patients revealed a complete occlusion of infarct-related artery with no clear contraindications to the study treatment. With the exception of thrombolysis in myocardial infarction (TIMI-3) recanalization 60 min after a bolus injection of mutant t-PA, the patients were given intracoronary UK in addition to mutant t-PA. The study comparisons were assessed using the following criteria: (1) 60-min assessment of recanalization rates, mutant t-PA vs UK; (2) time interval from initiation of thrombolysis to recanalization, mutant t-PA vs UK; (3) angiographic reocclusion rates within 1 month, mutant t-PA alone vs UK vs mutant t-PA plus UK; and (4) intracerebral hemorrhage rates, mutant t-PA alone vs UK vs mutant t-PA plus UK. There were no significant differences in the recanalization rates between mutant t-PA and UK, but there was a significant reduction in the time to recanalization with mutant t-PA (31.8 +/- 12.7 min) compared with UK (56.5 +/- 6.3 min). There was a significant difference in the reocclusion rates among the 3 treatment groups (20% mutant t-PA alone vs 4% UK vs 0% mutant t-PA plus UK). On the other hand, no significant differences in intracerebral hemorrhage rates among the 3 treatments were observed. In conclusion, thrombolytic therapy with a bolus injection of mutant t-PA achieved more rapid recanalization, but treatment with mutant t-PA led to a high rate of reocclusion.


Detecting cavitation in mercury exposed to a high-energy pulsed proton beam.
The Oak Ridge National Laboratory Spallation Neutron Source employs a high-energy pulsed proton beam incident on a mercury target to generate short bursts of neutrons. Absorption of the proton beam produces rapid heating of the mercury, resulting in the formation of acoustic shock waves and the nucleation of cavitation bubbles. The subsequent collapse of these cavitation bubbles promote erosion of the steel target walls. Preliminary measurements using two passive cavitation detectors (megahertz-frequency focused and unfocused piezoelectric transducers) installed in a mercury test target to monitor cavitation generated by proton beams with charges ranging from 0.041 to 4.1 muC will be reported on. Cavitation was initially detected for a beam charge of 0.082 muC by the presence of an acoustic emission approximately 250 mus after arrival of the incident proton beam. This emission was consistent with an inertial cavitation collapse of a bubble with an estimated maximum bubble radius of 0.19 mm, based on collapse time. The peak pressure in the mercury for the initiation of cavitation was predicted to be 0.6 MPa. For a beam charge of 0.41 muC and higher, the lifetimes of the bubbles exceeded the reverberation time of the chamber ( approximately 300 mus), and distinct windows of cavitation activity were detected, a phenomenon that likely resulted from the interaction of the reverberation in the chamber and the cavitation bubbles.


Atomic force microscopy reveals new biophysical markers for monitoring subcellular changes in oxidative injury: Neuroprotective effects of quercetin at the nanoscale.
Oxidative stress has been recognised as an important pathological mechanism underlying the development of neurodegenerative diseases. The biomarkers for assessing the degree of oxidative stress have been attracting much interest because of their potential clinical relevance in understanding the cellular effects of free radicals and evaluation of the efficacy of drug treatment. Here, an interdisciplinary approach using atomic force microscopy (AFM) and cellular and biological molecular methods were used to investigate oxidative damage in P19 neurons and to reveal the underlying mechanism of protective action of quercetin. Biological methods demonstrated the oxidative damage of P19 neurons and showed that quercetin improved neuronal survival by preventing H2O2-induced p53 and Bcl-2 down-regulation and modulated Akt and ERK1/2 signalling pathways. For the first time, AFM was employed to evaluate morphologically (roughness, height, Feret dimension) and nanomechanical (elasticity) properties in H2O2-induced neuronal damage. The AFM analysis revealed that quercetin suppressed H2O2-provoked changes in cell membrane elasticity and morphological properties, thus confirming its neuroprotective activity. The obtained results indicate the potential of AFM-measured parameters as a biophysical markers of oxidative stress-induced neurodegeneration. In general, our study suggests that AFM can be used as a highly valuable tool in other biomedical applications aimed at screening and monitoring of drug-induced effects at cellular level.


Observations on filarial infections and parous rates of anthropophilic blackflies in Guatemala, with reference to the transmission of Onchocerca volvulus.
In Guatemala, in areas of different onchocerciasis endemicity and outside the endemic zone, the main anthropophilic blackfly species Simulium ochraceum, S. metallicum, S. callidum and S. gonzalezi were examined for infections with Onchocerca volvulus, other filariae, and non-filarial parasites. Third stage larvae, indistinguishable from those of O. volvulus were found only in 3 females of S. ochraceum out of 3,513 examined. In S. metallicum, 2 females out of 3,121 dissected harboured infective larvae of another filaria species, morphologically different from O. volvulus. Thoracic infections were encountered in all four Simulium species. Only in S. ochraceum was there a correlation between the infection rates in the human and in the fly populations. In the endemic zone, up to 15% of the parous flies were infected, against none in the non-endemic area. Parous S. metallicum showed low over-all infection rates of 0.6 to 2.6%, and had infections also outside the endemic zone, but these could not have been of human origin. Non-filarial infections, including fungi of the ovaries, ciliates, mermithids, nematodes, were commonly observed in Guatemalan blackflies. Parous rates were 40% in S. ochraceum, 23% in S. metallicum, 39% in S. callidum, and 49% in S. gonzalezi. The size of the follicular relics showed a daily cycle in S. ochraceum. They were usually large in flies biting man in the afternoon, but small in flies biting in the morning. This suggests that the flies found a new host the same day, or the morning after they had deposited their eggs.


Adherence with controller medication in adults with asthma - impact of hospital admission for acute exacerbation.
Uncontrolled asthma is associated with higher risk of hospital admissions and death. Low adherence to inhaled corticosteroid (ICS), the cornerstone of asthma therapy, is well-documented. Our aim was to investigate if hospital admission with an acute exacerbation of asthma changes ICS adherence. This retrospective cohort study comprises 241 patients hospitalized with an asthma exacerbation over 12 months (May 2019-April 2020). The primary outcome was proportion of ICS adherent patients, defined as Medication Possession Ratio (MPR) ≥80%, in the six-month period before and after admission. The pre- to post-admission proportion of ICS adherent patients increased from 10% to 13% (p = 0.25) and the mean ICS MPR increased from 34% to 42% (p < 0.001). Different patterns of post-discharge adherence were observed, as adherent patients remained adherent, while patients with poor pre-admission adherence increased their adherence during two months after discharge followed by a decline in MPR. Co-variates such as sex, age, body mass index (BMI), GINA 2020-treatment step did not predict improvement in adherence after discharge. Admission with an asthma exacerbation did not increase the proportion of patients adherent with controller medication, primarily ICS. Although an improvement in adherence was initially seen primarily in previously poorly adherent patients, this increase was transient as it decreased over time post-discharge.


Facilitation of postischemic reperfusion with alpha-PBN: assessment using NMR and Doppler flow techniques.
We examined the effects of the free radical spin trap N-tert-butyl-alpha-phenylnitrone (PBN) on focal cerebral ischemia/reperfusion injury in halothane-anesthetized rats. Ninety minutes after middle cerebral artery occlusion by an intraluminal filament, the artery was reperfused. Intravenous injections of 25 mg/kg PBN 5 min before and 30 min after insertion of the filament significantly attenuated the lesion volume measured 24 h after ischemia. During ischemia and during the first 30 min after reperfusion, cerebral blood volume and blood flow were measured by volume-sensitive and newly developed flow-sensitive magnetic resonance imaging (MRI) techniques and by laser-Doppler flowmetry. In all animals the area of decreased blood flow was larger than the area of decreased volume by a factor of 2.2. The area of the postreperfusion flow deficits matched the final lesion volumes at 24 h measured histologically much better than did the blood volume deficits in both saline and PBN-treated animals. Reperfusion led to a return of blood flow and volume to values close to the contralateral side in the PBN-treated animals, in contrast to the saline-treated control group. We conclude that in focal ischemia/reperfusion PBN provides protection of the vascular endothelium, leading to enhanced postischemic reperfusion. The implication of this is that the vascular endothelium may be a primary target for the damaging action of free radicals given the protection afforded by putative spin traps.


Radiological evaluation of the morphological changes of root canals shaped with ProTaper for hand use and the ProTaper and RaCe rotary instruments.
This study evaluated, by means of the radiography examination, the occurrence of deviations in the apical third of root canals shaped with hand and rotary instruments. Sixty mandibular human molars were divided into three groups. The root canals in group 1 were instrumented with ProTaper (Dentsply/Maillefer, Ballaigues, Switzerland) for hand use, group 2 with ProTaper and group 3 with RaCe. The images obtained by double superimposition of the pre- and postoperative radiographs were evaluated by two endodontists with the aid of a magnifier-viewer and a fivefold magnifier. Statistical analysis was performed using the Fisher-Freeman-Halton. The instrumentation using the ProTaper for hand use showed 25% of the canals with a deviation in the apical third, as did the ProTaper, while the corresponding figure for the RaCe (FKG Dentaire, La-Chaux-de-Fonds, Switzerland) was 20%, but these results were not statistically significant. There was no correlation between the occurrence of deviations in the apical third and the systems used.


Conditional lethality of a yeast strain expressing human RHOA in place of RHO1.
The yeast RHO1 GTPase, which has 72% amino acid sequence identity with its human counterpart, RHOA, is essential for growth, although the reason has not been investigated. We report here that yeast strains that rely solely on expression of human RHOA in place of RHO1 are able to grow at 23 degrees C but grow neither at 37 degrees C nor in the presence of 300 mM CaCl2 even at 23 degrees C. Measurements of steady-state protein levels indicate that inability to grow at the restrictive temperature is not due to instability of the protein. Homolog scanning with the two GTPases identified a small, 27-residue region of RHO1 which, when substituted into RHOA, confers full function in yeast. This region corresponds to the alpha 3-helix loop 7 region of RAS; the same region was reported to determine specificity of function between GTPases of the RAB family, Sec4p and Ypt1p. By examining the phenotype of RHOA substitution strains at nonpermissive temperature, we found evidence suggesting that the normal function of RHO1 is to maintain osmotic integrity.


Recent trends in the use of polysaccharides for improved delivery of therapeutic agents: pharmacokinetic and pharmacodynamic perspectives.
New and innovative methods of delivery of therapeutic agents using polysaccharides have been recently developed, which target site of action, increase the intensity and/or prolong pharmacologic action, and/or reduce toxicity of small molecule drugs, proteins, or enzymes. This review is focused on the role of dextran, pullulan, and mannan polysaccharides in such applications. While dextran and pullulan are glucose polymers with different glucosidic linkages, mannan is composed of mannose units. In terms of pharmacokinetics of the carriers themselves, molecular weight (MW), electric charge, various chemical modifications, and degree of polydispersity and/or branching would mostly determine their fate in vivo. Generally, large MW polysaccharides (MWs > or = 40 kD) have low clearance and relatively long plasma half life, resulting in accumulation in reticuloendothelial or tumor tissues. The tumor accumulation in most cases is a passive targeting due to "enhanced permeation and retention" of macromolecules by tumors. Additionally, drugs such as anticancer agents may be actively targeted to specific cells by polysaccharides to which appropriate ligands are attached. In terms of mode of use, polysaccharides have been utilized in a variety of innovative ways for improvement of drug delivery. Their most important application has been as carriers for preparation of macromolecular prodrugs that are normally inactive and need to release the active drug at the site(s) of interest. Also, they have been used for preparation of macromolecule-protein conjugates, which may retain the activity of the proteins, in order to increase the duration of effect and decrease the immunogenicity of proteins. Several other new applications, such as polysaccharide-anchored liposomal formulations, have also been gained attention recently and are briefly reviewed here. Finally, four recent examples of polysaccharide-based delivery systems involving specific drugs/imaging agents are reviewed in detail in terms of their development, pharmacokinetics, and pharmacodynamics. Collectively, these data suggest that macromolecular polysaccharides are promising agents for improving drug delivery.


Cardiac oxygen limitation during an acute thermal challenge in the European perch: effects of chronic environmental warming and experimental hyperoxia.
Oxygen supply to the heart has been hypothesized to limit cardiac performance and whole animal acute thermal tolerance (CTmax) in fish. We tested these hypotheses by continuously measuring venous oxygen tension (Pvo2) and cardiovascular variables in vivo during acute warming in European perch (Perca fluviatilis) from a reference area during summer (18°C) and a chronically heated area (Biotest enclosure) that receives warm effluent water from a nuclear power plant and is normally 5-10°C above ambient (24°C at the time of experiments). While CTmax was 2.2°C higher in Biotest compared with reference perch, the peaks in cardiac output and heart rate prior to CTmax occurred at statistically similar Pvo2 values (2.3-4.0 kPa), suggesting that cardiac failure occurred at a common critical Pvo2 threshold. Environmental hyperoxia (200% air saturation) increased Pvo2 across temperatures in reference fish, but heart rate still declined at a similar temperature. CTmax of reference fish increased slightly (by 0.9°C) in hyperoxia, but remained significantly lower than in Biotest fish despite an improved cardiac output due to an elevated stroke volume. Thus, while cardiac oxygen supply appears critical to elevate stroke volume at high temperatures, oxygen limitation may not explain the bradycardia and arrhythmia that occur prior to CTmax Acute thermal tolerance and its thermal plasticity can, therefore, only be partially attributed to cardiac failure from myocardial oxygen limitations, and likely involves limiting factors on multiple organizational levels.


[Radioresistance mechanisms of Micrococcus radiodurans].
The modern conceptions on the molecular mechanisms of Micrococcus radiodurans viability under the action of ionized radiation have been considered. Factors providing a high level of the bacterium radioresistance-the peculiarities of the cell wall structure, membranes, DNA, the redundancy of genetic information, the multiplicity of sites of DNA attachment to the membrane, a high level of antioxidant and antiradical systems-have been analysed. It has been shown that the efficiency of accurate, error-free, well balanced DNA repair system in connection with M. radiodurans properties mentioned provides a high radiation resistance of this microorganism.


Synthesis of α-Methylene-β-Lactams via PPh3-Catalyzed Umpolung Cyclization of Propiolamides.
We report herein a facile synthesis of α-methylene-β-lactams. Thus, under the catalysis of triphenylphosphine, a number of 2-propiolamidoacetates or α-propiolamido ketones in refluxing ethanol underwent umpolung cyclization to afford the corresponding 4-substituted 3-methyleneazetidin-2-ones in high yields.


Peroperative blood salvage.
The procedure of autotransfusion includes the collection of the patient's own blood before, during or after surgery with the aim of retransfusing it either immediately or postoperatively. The increasing demands on the blood banks as well as the growing fear of transfusion transmitted diseases have created a new interest in autotransfusion. Application of autotransfusion will reduce the need for homologous blood and thereby cut the cost.


German validation of Quality of Life after Brain Injury (QOLIBRI) assessment and associated factors.
The consequences of traumatic brain injury (TBI) for health-related quality of life (HRQoL) are still poorly understood, and no TBI-specific instrument has hitherto been available. This paper describes in detail the psychometrics and validity of the German version of an internationally developed, self-rated HRQoL tool after TBI-the QOLIBRI (Quality of Life after Brain Injury). Factors associated with HRQoL, such as the impact of cognitive status and awareness, are specifically reported. One-hundred seventy-two participants after TBI were recruited from the records of acute clinics, most of whom having a Glasgow Coma Scale (GCS) 24-hour worst score and a Glasgow Outcome Scale (GOSE) score. Participants had severe (24%), moderate (11%) and mild (56%) injuries as assessed on the GCS, 3 months to 15 years post-injury. The QOLIBRI uses 37 items to measure "satisfaction" in the areas of "Cognition", "Self", "Daily Life and Autonomy", and "Social Relationships", and "feeling bothered" by "Emotions"and "Physical Problems". The scales meet standard psychometric criteria (α = .84 to .96; intra-class correlation-ICC = .72 to .91). ICCs (0.68 to 0.90) and αs (.83 to .96) were also good in a subgroup of participants with lower cognitive performance. The six-subscale structure of the international sample was reproduced for the German version using confirmatory factor analyses and Rasch analysis. Scale validity was supported by systematic relationships observed between the QOLIBRI and the GOSE, Patient Competency Rating Scale for Neurorehabilitation (PCRS-NR), Hospital Anxiety and Depression Scale (HADS), Profile of Mood States (POMS), Short Form 36 (SF-36), and Satisfaction with Life Scale (SWLS). The German QOLIBRI contains novel information not provided by other currently available measures and has good psychometric criteria. It is potentially useful for clinicians and researchers, in post-acute and rehabilitation studies, on a group and individual level.


The experience of a tertiary level hospital in the 2023 Turkey double earthquake zone; management of 1,092 musculoskeletal injuries in the first week.
The double earthquakes that occurred on February 6, 2023, are currently called the disaster of the century, in Turkey. This study is the first to report the experiences in the treatment of orthopedic emergency patients hospitalized in Adana City Training and Research Hospital (ACH), the largest tertiary hospital in the region. The study included the retrospective analysis of the files of the victims of the earthquakes admitted to the ACH between February 6, 2023, and February 13, 2023. The age, gender, time of admission, types and localization of injuries, treatment modalities of earthquake victims, and orthopedic surgical treatment data were recorded. In the first week of the quakes, 3,699 patients were admitted to the ER with earthquake-related injuries. A total of 1,092 patients with musculoskeletal injuries were hospitalized, and 827 (75.7%) received orthopedic surgery. Surgical procedures included wound debridement under anesthesia (n=392, 47.4%), large bone fractures and/or pelvic ring fractures (n=224, 27.1%), fasciotomies (n=327, 69.1%), and amputations (n=121, 14.6%). Although Orthopedics and Traumatology Clinic staff have the highest workload, all hospital personnel should be equipped with basic orthopedic approaches related to the disaster. We believe that taking a more active role in the follow-up of orthopedic patients will help improve the management of the chaotic processes and increase overall treatment success.


The relation between response rates and reinforcement rates in a multiple schedule.
In a multiple schedule, exteroceptive stimuli change when the reinforcement schedule is changed. Each performance in a multiple schedule may be considered concurrent with other behavior. Accordingly, two variable-interval schedules of reinforcement were arranged in a multiple schedule, and a third, common variable-interval schedule was programmed concurrently with each of the first two. A quantitative statement was derived that relates as a ratio the response rates for the first two (multiple) variable-interval schedules. The value of the ratio depends on the rates of reinforcement provided by those schedules and the reinforcement rate provided by the common variable-interval schedule. The following implications of the expression were evaluated in an experiment with pigeons: (a) if the reinforcement rates for the multiple variable-interval schedules are equal, then the ratio of response rates is unity at all reinforcement rates of the common schedule; (b) if the reinforcement rates for the multiple schedules are unequal, then the ratio of response rates increases as the reinforcement rate provided by the common schedule increases; (c) the limit of the ratio is equal to the ratio of the reinforcement rates. Satisfactory confirmation was obtained for the first two implications, but the third was left in doubt.


Cigarette smoking-attributable mortality and years of potential life lost--United States, 1990.
Cigarette smoking is the single most preventable cause of premature death in the United States. An estimated 390,000 smoking-attributable deaths in the United States occurred in 1985, and more than 434,000 deaths occurred in 1988; in 1988, an estimated 1,198,887 years of potential life lost (YPLL) before age 65 were attributed to smoking. To estimate the national impact of cigarette smoking on mortality and YPLL, calculations were performed using the Smoking-Attributable Mortality, Morbidity, and Economic Cost (SAMMEC) software. This report summarizes the results of this analysis.


[Comparative Experiment and Spectrometric Analysis on Characteristics of Enclosed Inductively Coupled Plasma].
In the present paper, the spectrum analytic method was used to comparatively study the ICP electron density distribution through two typical ICP sources (spiral-type and planar-type) in closed quartz chamber. The E-H mode transition of inductively coupled plasma and power coupling efficiency were researched through the change in the relative intensity of argon ion spectral line (476. 45 nm). Electron density distribution on the antennas-vertical plane of different ICP source was calculated through non-hydrogen-like Stark broadening of spectral line method. The test results show that the ICP electronic density distribution in H-mode discharge is significantly impacted by skin current of alternating magnetic field. The skin depth decreases with the increase in discharge power. Meanwhile, the bulk of the main plasma narrows and electron density increases. On the vertical plane of the antenna, electron density distribution presents center-symmetry by spiral-ICP source and bimodal by planar-ICP source. The power coupling efficiency is directly affected bysource antenna shape and capacitive coupling effect. The relative intensity of the argon spectrum shows that the power coupling efficiency of spiral-type source is lower than that of planar-type source. The proposed experimental method provides a way to obtain a plasma source in closed quartz cube chamber with the highest electron density ranging from 1. 4X 10(17) to 2. 5 X 10(17) m-3 (spiral-ICP source) and 1. 8 X 10(17) to 3. 0 X 10(17) m-3 (planar-ICP source).


Predicting Presynaptic and Postsynaptic Neurotoxins by Developing Feature Selection Technique.
Presynaptic and postsynaptic neurotoxins are proteins which act at the presynaptic and postsynaptic membrane. Correctly predicting presynaptic and postsynaptic neurotoxins will provide important clues for drug-target discovery and drug design. In this study, we developed a theoretical method to discriminate presynaptic neurotoxins from postsynaptic neurotoxins. A strict and objective benchmark dataset was constructed to train and test our proposed model. The dipeptide composition was used to formulate neurotoxin samples. The analysis of variance (ANOVA) was proposed to find out the optimal feature set which can produce the maximum accuracy. In the jackknife cross-validation test, the overall accuracy of 94.9% was achieved. We believe that the proposed model will provide important information to study neurotoxins.


A self-instructional approach to gross anatomy: evaluation of five years experience.
A largely self-instructional teaching method in gross anatomy for dental students, developed and tested over five years at the University of Louisville, is presented and evaluated. The merits of the method include reduced faculty teaching load, the potential to accommodate increased numbers of students without comparable increases in faculty or physical plant, apparent improvement in the quality of instruction, student satisfaction, early identification of marginal students, and conservation of cadavers.


Effects of hyaluronic acid on the polymorphonuclear leukocyte (PMN) release of active oxygen and protection of bovine corneal endothelial cells from activated PMNs.
The goal of this study was to evaluate the function of hyaluronic acid (HA) on the active oxygen release from polymorphonuclear leukocytes (PMNs) and the protective effect of bovine corneal endothelial cells (BCEC) from activated PMNs. We used HA with three different molecular weights (MW 700,000, 2,000,000, and 4,000,000) and five different concentrations (0, 0.1, 1, 2, and 3 mg/ml). We evaluated the amount of released superoxide from activated PMNs by using dismutase-inhibitable ferricytochrome C reduction. To compare the property and protective effect of HA with those of other viscoelastic substances, we used the same concentration of methylcellulose. HA suppressed superoxide release from PMNs and protected BCEC from activated PMNs in a dose-dependent, rather than a molecular weight-dependent, manner. The effect of HA reached almost a plateau at concentration above 2 mg/ml. However, methylcellulose, another viscoelastic substance, showed a similar effect. Therefore, it seems that the suppression of superoxide released from PMNs is not a property that is unique to HA, but is a general property of viscoelastic substances. Our results indicate that the action mechanism of HA proceeds not only through cell surface HA-receptor. We think that HA also acts as a physical barrier and/or a scavenger of superoxide.


Dual-target one-step nested PCR for sensitive detection of SARS-CoV-2 nucleic acids.
The Corona Virus Disease reported in 2019 (COVID-19) poses a significant threat to human and public health. Its early and accurate detection can reduce the spread and recurrence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Real-time reverse transcription fluorescent quantitative polymerase chain reaction (RT-qPCR) is the "gold standard" for detecting the nucleic acid of SARS-CoV-2. This study developed and tested a dual-target (ORF1ab and N gene) one-step nested RT-qPCR (DTO-N-PCR) to detect SARS-CoV-2. Ten-fold serial dilutions of mixed synthetic DNA from SARS-CoV-2 ORF1ab and N gene were used as templates to test the sensitivity of DTO-N-PCR. Its specificity was subsequently tested using throat swab specimens from 10 COVID-19 patients and 35 healthy participants. DTO-N-PCR was more sensitive and specific than conventional RT-qPCR. It has unique features, including a dual-target (ORF1ab and N gene), rapid one-step operation of reverse transcription and PCR, four pairs of inner and outer primers, and specific probes. These features aid in its rapid, accurate, and efficient detection of SARS-CoV-2 RNA.


A cryopyrin-associated periodic syndrome with joint destruction.
Describe four generations (11 members) of a family with a cryopyrin-associated periodic syndrome (CAPS), including joint destruction, associated with a CIAS1-gene mutation and good responses to anakinra. In addition to detailed questioning and physical examination, six family members underwent haematological, immunological and biochemical testing. Exon 3 of the CIAS1 gene was sequenced in search of a mutation in the 1q44 region. During childhood or adolescence, four family members developed different combinations of the following CAPS manifestations: deafness (3/4); arthritis (4/4) with joint destruction for two of them; nervous (cerebral demyelinization, 2/4), cutaneous (livedo and/or urticaria, 3/4) and eye lesions (episcleritis and/or papilloedema, 4/4); IgA hypergammaglobulinaemia (4/4) and inflammatory syndrome (3/4). Sequencing of six family members' CIAS1-gene exon 3 identified a heterozygous mutation, c.1043C > T. Pertinently, this CAPS is distinct from chronic infantile neurological cutaneous and arthritis syndrome/neonatal onset multisystemic inflammatory disease syndrome and Muckle-Wells syndrome (MWS), which also result from exon 3 mutations in this gene. Moreover, this family did not have the usual neurological manifestations, typical morphological features and frequent amyloidosis of MWS. We describe a previously unreported form of CAPS with atypical neurological signs, joint destruction and livedo. This observation extends the clinical spectrum associated with CIAS1 mutations. Anakinra, an interleukin-1-receptor antagonist, prescribed to two family members, was highly effective.


[Clinicopathological experiences in oncologic diseases].
Authors on the base of the study of clinical history and autopsy protocols of 260 patients died in 1974 in the Institute of Oncology of Hungary from oncological diseases established, that the proportion of decised younger 30 years and the number of those older 70 years increased in comparison with 1964. In the autopsy material the most frequent were tumours of the lymphoid-myeloid system, then followed the frequency of the tumours of the breast and urogenital tract, the least frequent were the tumours of the gastrointestinal tract. Number of the primary multiplex tumours during the last 10 years increased from 1,5 per cent to 5,5 per cent. In 23,5 per cent of the cases medica negligence or that of the patient itself could be proved. The clinical and the pathological diagnosis did not correlate in 35,9 per cent of the cases studied. The most common unrecognized complication was pneumonia. Surgical treatment appeared to be most effective in cases of the cancer of the breast. The average age of the patients suriving for a longer period after the operation was 62,8 years, which seems to evidence, that prognosis of oncological diseases in older ages is better than in younger. In comparison with the data in 1964 number of cases with five year surviving increased by 3,7 per cent. This was striking first of all in cases of lymphoid-myeloid tumours.


Relationship of sonographic wall components of the brachial artery to hypertension and coronary atherosclerosis.
The aim of this study was to determine whether sonographically assessed intimal (echodense, ED) or medial (echolucent, EL) thickening of the brachial artery is associated with coronary artery disease (CAD) and/or arterial hypertension (HT). In 201 patients the ED and EL wall components, as well as the total wall thickness of the brachial artery, were measured with high-resolution ultrasound (13 MHz). According to the presence or absence of CAD and HT, the patients were divided into four groups: no HT and no CAD (n = 26, group 1), CAD (> or = 30% diameter stenosis in > or = 1 major branch) only (n = 63, group 2), HT only (n = 34, group 3), and HT and CAD (n = 78, group 4). EL (p < 0.001) and combined wall thickness (p < 0.001), but not the ED wall component, were significantly different between the groups, with the highest values occurring in group 4. On logistic regression analyses adjusting for age, coronary risk factors and body mass index, EL, but not ED, thickness correlated independently with the presence of CAD (p = 0.04) and HT (p < 0.001). High-resolution ultrasound examination of the brachial artery wall structure may contribute to the noninvasive assessment of early atherosclerosis.


Preparation of Plasmonic Ag@PS Composite via Seed-Mediated In Situ Growth Method and Application in SERS.
The colloidal polystyrene (PS) was synthesized and decorated with silver nanoparticles (Ag NPs). The plasmonic Ag@PS nanocomposite was prepared by loading Ag NPs on PS microsphere through a seed-mediated in situ growth route. The property of Ag NPs deposited on the PS microsphere could be precisely controlled by adjusting the concentration of the chemicals used in the growth medium. The growth step is only limited by the diffusion of growing species in the growth media to the surface of the Ag seed. The Ag@PS prepared via the in situ growth method exhibited two advantages compared with the self-assembled PS/Ag. First, the high-density of Ag NPs were successfully deposited on the surface of PS as the electroless-deposited Ag seed process, which brings nearly three times SERS enhancement. Second, the rapid preparation process for in situ growth method (half an hour, 10 h for the self-assembled method). The PS/Ag could detect Nile blue A (NBA) down to 10-7 M by SERS. Furthermore, the plasmonic Ag@PS SERS substrate was used for pesticide identification. The on-site monitoring malachite green (MG) from fish was achieved by portable Raman spectrometer, and the limit of detection (LOD) was 0.02 ppm. The Ag@PS substrate has also shown capability for simultaneously sensing multiple pesticides by SERS.


EGCG inhibits Cd(2+)-induced apoptosis through scavenging ROS rather than chelating Cd(2+) in HL-7702 cells.
Epigallocatechin-3-gallat (EGCG), the major catechin in green tea, shows a potential protective effect against heavy metal toxicity to humans. Apoptosis is one of the key events in cadmium (Cd(2+))-induced cytotoxicity. Nevertheless, the study of EGCG on Cd(2+)-induced apoptosis is rarely reported. The objective of this study was to clarify the effect and detailed mechanism of EGCG on Cd(2+)-induced apoptosis. Normal human liver cells (HL-7702) were treated with Cd(2+) for 21 h, and then co-treated with EGCG for 3 h. Cell viability, apoptosis, intracellular reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential (MMP) and caspase-3 activity were detected. On the other hand, the chelation of Cd(2+) with EGCG was tested by UV-Vis spectroscopy analysis and Nuclear Magnetic Resonance ((1)H NMR) spectroscopy under neutral condition (pH 7.2). Cd(2+) significantly decreased the cell viability and induced apoptosis in HL-7702 cells. Conversely, EGCG co-treatment resulted in significant inhibition of Cd(2+)-induced reduction of cell viability and apoptosis, implying a rescue effect of EGCG against Cd(2+) poisoning. The protective effect most likely arises from scavenging ROS and maintaining redox homeostasis, as the generation of intracellular ROS and MDA is significantly reduced by EGCG, which further prevents MMP collapse and suppresses caspase-3 activity. However, no evidence is observed for the chelation of EGCG with Cd(2+) under neutral condition. Therefore, a clear conclusion from this work can be made that EGCG could inhibit Cd(2+)-induced apoptosis by acting as a ROS scavenger rather than a metal chelating agent.


A study of neural artistic style transfer models and architectures for Indian art styles.
Neural Style Transfer (NST) has been a widely researched topic as of late enabling new forms of image manipulation. Here we perform an extensive study on NST algorithms and extend the existing methods with custom modifications for application to Indian art styles. In this paper, we aim to provide a comprehensive analysis of various methods ranging from the seminal work of Gatys et al which demonstrated the power of Convolutional Neural Networks (CNNs) in creating artistic imagery by separating and recombining image content and style, to the state of the art image-to-image translation models which use Generative Adversarial Networks (GANs) to learn the mapping between two domain of images. We observe and infer based on the results produced by the models on which one could be a more suitable approach for Indian art styles, especially Tanjore paintings which are unique compared to the Western art styles. We then propose the method which is more suitable for the domain of Indian Art style along with custom architecture which includes an enhancement and evaluation module. We then present evaluation methods, both qualitative and quantitative which includes our proposed metric, to evaluate the results produced by the model.


The replication timing program in the hands of two HDACs.
In eukaryotes, duplication of genomic information depends on the sequential activation of multiple replication origins distributed along the chromosomes. Replication origins differ in initiation time, chromatin structure and three-dimensional position in the nucleus. Recently, we have performed a systematic analysis of the role of histone deacetylases (HDACs) in the regulation of origin activity in budding yeast. We have found that the epigenetic regulation of repetitive sequences is a key determinant of the DNA replication program. Indeed, our study revealed that two histone deacetylases, Rpd3 and Sir2, have opposite effects on the replication timing program. Rpd3 delays initiation at late origins, whereas Sir2 promotes efficient activation of early origins. Remarkably, we also found that Rpd3 and Sir2 regulate initiation at ~200 replication origins located within the ribosomal DNA (rDNA) array. We propose that this epigenetic regulation of repetitive origins controls the replication timing program by modulating the availability of limiting initiation factors.


Heinz body formation in cats fed baby food containing onion powder.
To determine whether cats fed baby food with onion powder develop Heinz bodies and anemia and to establish a dose-response relation between dietary onion powder content and Heinz body formation. Prospective study. 42 healthy, adult, specific-pathogen-free cats. Commercial baby food with and without onion powder was fed to 2 groups of 6 cats for 5 weeks. Heinz body percentage, PCV, reticulocyte percentage, turbidity index, and methemoglobin and reduced glutathione concentrations were determined twice weekly and then weekly for 4 weeks following removal of the diet. For the dose-response study, 5 groups of 6 cats were fed a canned diet for 2 months that contained 0, 0.3, 0.75, 1.5, or 2.5% onion powder. Heinz body percentage, PCV, and reticulocyte percentage were determined twice weekly. Compared with cats fed baby food without onion powder, cats ingesting baby food with onion powder had significantly higher Heinz body percentages that peaked at 33 to 53%. Methemoglobin concentration also significantly increased but did not exceed 1.2%. Glutathione concentration, PCV, and food intake did not differ between the 2 groups. Rate and degree of Heinz body formation differed significantly between various onion powder concentrations fed. Compared with 0% onion powder, the diet with 2.5% onion powder caused a significant decrease in PCV and an increased punctate reticulocyte percentage. Baby food or other foods containing similar amounts of onion powder should be avoided for use in cats because of Heinz body formation and the potential for development of anemia, particularly with high food intake. Cats with diseases associated with oxidative stress may develop additive hemoglobin damage when fed baby food containing onion powder.


[Intervertebral disc calcification in childhood].
Author describes a case of calcification of the intervertebral disk in a child, observed simultaneously in two segments on the dorsal spine. During a long observation the signs of remission were observed. The case was thought worthy to be published because of the rare occurrence and the problematic differential diagnosis.


Improved cross-talk suppression for digitally enhanced interferometry using Golay complementary pairs.
We demonstrate digitally enhanced interferometry with better than 100 dB mean cross-talk suppression with Golay complementary pairs using a combination of numerical simulations and experiments. These results exceed previously reported cross-talk suppression using conventional maximal length sequences by more than 48 dB.


Structure and expression of the overlapping ND4L and ND5 genes of Neurospora crassa mitochondria.
Genes homologous to the mammalian mitochondrial NADH dehydrogenase subunit genes ND4L and ND5 were identified in the mitochondrial genome of the filamentous fungus Neurospora crassa, and the structure and expression of these genes was examined. The ND4L gene (interrupted by one intervening sequence) potentially encodes an 89 residue long hydrophobic protein that shares about 26% homology (or 41% homology if conservative amino acid substitutions are allowed) with the analogous human mitochondrial protein. The ND5 gene (which contains two introns) encodes a 715 residue polypeptide that shares 23% homology with the human analogue; a 300 amino acid long region is highly conserved (50% homology) in the two ND5 proteins. The stop codon of the ND4L gene overlaps the initiation codon of the downstream ND5 gene, and the two genes are cotranscribed and probably cotranslated. A presumed mature dicistronic (ND4L plus ND5) RNA was detected. The postulated mRNA (about 3.2 kb) contains 5' and 3' non-coding regions of about 86 and 730 nucleotides, respectively; this species is generated from very large precursor RNAs by a complex processing pathway. The ND4L and ND5 introns are all stable after their excision from the precursor species.


[Stereotyping of overweight children by their contemporaries].
Childhood obesity represents not only a health risk but results also in social exclusion and stigmatization. While several studies have been conducted on this topic in America [1-3], there are hardly any German trials on the social impact of obesity in childhood and adolescence. This study investigates whether and how obese children and adolescents are stigmatized by their contemporaries because of their corpulence. A total of 454 (230 female, 224-male) children and adolescents aged 10-15 years from high and secondary modern schools in a Southern German university city were asked about how they appreciate their obese contemporaries. The interviewees were asked to assess six photographs of girls and boys with regard to sympathy, playmate preference, activity, intelligence and attractiveness. Obese children were assessed far more negatively in all asked areas compared to normal weight healthy and physically disabled children respectively. They were also referred to as more dislikable, lazy, less intelligent, unalluring and less considerable as playmates. This applies particularly for the obese boy. Hence, negative stereotypization of obese people can already be observed in childhood and adolescence.


The Role of the Slit/Robo Signaling Pathway.
The Slit family is a family of secreted proteins that play important roles in various physiologic and pathologic activities via interacting with Robo receptors. Slit/Robo signaling was first identified in the nervous system, where it functions in neuronal axon guidance; nevertheless, an increasing number of studies have shown that Slit/Robo signaling even regulates other activities, such as angiogenesis, inflammatory cell chemotaxis, tumor cell migration and metastasis. Although the precise role of the ligand-receptor in organisms has been obscure and the conclusions drawn are sometimes paradoxical, tremendous advances in understanding the Slit/Robo signaling pathway have been made. As such, our review summarizes the characteristics of the Slit/Robo signaling pathway and its role in various cell types.


Temperature and food quality effects on growth, consumption and post-ingestive utilization efficiencies of the forest tent caterpillar Malacosoma disstria (Lepidoptera: Lasiocampidae).
Temperature and food quality can both influence growth rates, consumption rates, utilization efficiencies and developmental time of herbivorous insects. Gravimetric analyses were conducted during two consecutive years to assess the effects of temperature and food quality on fourth instar larvae of the forest tent caterpillar Malacosoma disstria Hübner. Larvae were reared in the laboratory at three different temperatures (18, 24 and 30 degrees C) and on two types of diet; leaves of sugar maple trees Acer saccharum Marsh. located at the forest edge (sun-exposed leaves) or within the forest interior (shade-exposed leaves). In general, larvae reared at 18 degrees C had lower growth rates and lower consumption rates than larvae reared at the warmer temperatures (24 and 30 degrees C). Moreover, the duration of the instar decreased significantly with increasing temperatures. Type of diet also affected the growth rates and amount of food ingested by larvae but did not affect the duration of the instar. Larvae fed sun-exposed leaves consumed more food and gained higher biomasses. Values of approximate digestibility and efficiency of conversion of ingested food were also higher when larvae were fed sun-exposed leaves. Higher growth rates with increasing temperatures were primarily the result of the shorter stadium duration. The higher growth rates of larvae fed sun-exposed leaves were possibly the result of stimulatory feeding and consequently greater food intake and also a more efficient use of food ingested. This study suggests that the performance of M. disstria caterpillars could be enhanced by warmer temperatures and higher leaf quality.


Evidence of Amniotic Epithelial Cell Differentiation toward Hepatic Sinusoidal Endothelial Cells.
Amniotic epithelial cells (AECs) represent a useful and noncontroversial source for liver-based regenerative medicine, as they can differentiate into hepatocytes upon transplantation into the liver. However, the possibility that AECs can differentiate into other liver cell types, such as hepatic sinusoidal endothelial cells (HSECs), has never been assessed. In order to test this hypothesis, rat- and human-derived AECs (rAECs and hAECs, respectively) were subjected to endothelial cell tube formation assay in vitro. Moreover, to evaluate differentiation in vivo, the retrorsine (RS) model of liver repopulation was used. Pyrrolizidine alkaloids (including RS) are known to target both hepatocytes and endothelial cells, inducing cell enlargement and inhibition of cell cycle progression. rAECs and hAECs were able to form capillary-like structures when cultured under proangiogenic conditions. For in vivo experiments, rAECs were obtained from dipeptidyl peptidase type IV (DPP-IV, CD26) donors and were transplanted into the liver of recipient CD26 negative animals pretreated with RS. rAEC-derived cells were engrafted in between hepatocytes and resembled HSECs as assessed by morphological analysis and the pattern of expression of CD26. Donor-derived CD26+ cells coexpressed HSEC markers RECA-1 and SE-1, while they lacked expression of typical hepatocyte markers (i.e., cytochrome P450, hepatocyte nuclear factor 4α). As such, these results provide the first evidence that AECs can respond to proangiogenic signals in vitro and differentiate into HSECs in vivo. Furthermore, they support the conclusion that AECs possesses great plasticity and represents a promising tool in the field of regenerative medicine both in the liver and in other organs.


Tetrathiafulvalene-based azine ligands for anion and metal cation coordination.
The synthesis and full characterization of two tetrathiafulvalene-appended azine ligands, namely 2-([2,2'-bi(1,3-dithiolylidene)]-4-yl)-6-((2,4-dinitrophenyl)hydrazono)methyl)pyridine (L1) and 5-([2,2'-bi(1,3-dithiolylidene)]-4-yl)-2-((2,4-dinitrophenyl)hydrazono)methyl)pyridine (L2) are described. The crystal structure of ligand L1 indicates that the ligand is completely planar with the presence of a strong intramolecular N3-H3···O1 hydrogen bonding. Titration experiments with inorganic anions showed that both ligands are suitable candidates for the sensing of fluoride anions. Ligand L2 was reacted with a Re(I) cation to yield the corresponding rhenium tricarbonyl complex 3. In the crystal structure of the newly prepared electroactive rhenium complex the TTF is neutral and the rhenium cation is hexacoordinated. The electrochemical behavior of the three compounds indicates that they are promising for the construction of crystalline radical cation salts.


Measurement invariance of Female Sexual Function Index: a study with heterosexual and lesbian Portuguese women.
The Female Sexual Function Index is a powerful screening tool for female sexual dysfunction extensively used worldwide. Nonetheless, its factorial structure and psychometric properties have been tested almost exclusively with heterosexual samples. The current study aimed to testing the original factorial structure, reliability and temporal stability in two samples of women (heterosexual and lesbian), and to assess the measurement invariance across sexual orientation. An online sample of 752 Portuguese women (376 lesbian women and 376 heterosexual women) recruited between May 2012 and 2013 participated in the study and completed a sociodemographic questionnaire and the FSFI. For temporal stability, 30 Portuguese women were recruited online in May 2017. Confirmatory factor analysis, reliability analysis and temporal stability were assessed independently for each sample. Measurement invariance (configural, metric, and scalar) was also assessed. Main findings for both samples corroborate the six-factor structure and revealed excellent levels of temporal stability, with Cronbach alphas and McDonalds Omega of .95 for heterosexual sample, and .96 for lesbian women sample. Results corroborate measurement invariance (configural, metric, and scalar) across sample type. Overall, the FSFI revealed a good-fit for the six-factor model in both heterosexual and women sample, with excellent levels of reliability and temporal stability, and showed measurement invariance across sexual orientation. These findings support the use of the FSFI with lesbian women.