Instability in progressive multiple sequence alignment algorithms.
Progressive alignment is the standard approach used to align large numbers of sequences. As with all heuristics, this involves a tradeoff between alignment accuracy and computation time. We examine this tradeoff and find that, because of a loss of information in the early steps of the approach, the alignments generated by the most common multiple sequence alignment programs are inherently unstable, and simply reversing the order of the sequences in the input file will cause a different alignment to be generated. Although this effect is more obvious with larger numbers of sequences, it can also be seen with data sets in the order of one hundred sequences. We also outline the means to determine the number of sequences in a data set beyond which the probability of instability will become more pronounced. This has major ramifications for both the designers of large-scale multiple sequence alignment algorithms, and for the users of these alignments.


A randomized controlled trial using surgical gloves to prevent chemotherapy-induced peripheral neuropathy by paclitaxel in breast cancer patients (AIUR trial).
Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of taxane treatment and can significantly affect patient quality of life. Currently, there are no effective treatments to alleviate symptoms of CIPN; thus, starting with prevention steps in high-risk patients is considered advantageous. However, for these prevention steps to be applicable to all patients, their side effects or accompanying discomforts should be minimal, and the intervention cost-effective. Compression therapy can be considered a prevention intervention, and using surgical gloves is feasible and cost-effective (approximately $0.6 per pair). Although previous studies on compression therapy using surgical gloves have reported decreased incidence of PN, these studies were non-randomized, limited to nab-paclitaxel treatment, and involved the use of small gloves, which may have caused discomfort. Therefore, this study aimed to assess the preventive effects of compression therapy using normal-sized surgical gloves on CIPN in patients treated with paclitaxel. This clinical trial is designed to evaluate the preventive effects of compression therapy using surgical gloves on CIPN in women with stage II-III breast cancer who received paclitaxel chemotherapy for at least 12 weeks. This multicenter, randomized-controlled, open-label study will be conducted in six academic hospitals. Patients with medication or a medical history related to neuropathy or hand disease will be excluded. The primary outcome will be the preventive effect of compression therapy using surgical gloves, measured based on changes in the neurotoxicity component of the Functional Assessment of Cancer Therapy-Taxane questionnaire. Furthermore, we will assess the National Cancer Institute's Common Terminology Criteria for Adverse Events grade of CIPN after 6 months. Notably, the estimated sample size, based on a p-value < 0.025 and statistical power of 0.9, will consist of 104 patients (52 per group), accounting for a 10% sample loss. This intervention can be easily implemented in clinical practice and may serve as a preventive strategy for CIPNs with strong patient adherence. If successful, this intervention could improve the quality of life and treatment adherence in patients receiving chemotherapy that can induce PN, extending beyond paclitaxel treatment alone. ClinicalTrials.gov, NCT05771974; Registered on March 16, 2023.


Microplastics - An emerging contaminants for algae. Critical review and perspectives.
In recent decades, micro- and nanoplastics (MNPs) became persistent contaminants of emerging concern to the environment. These xenobiotic are found in all components of environment, including living organisms. Ubiquitous contamination of aquatic ecosystems with these pollutants is studied worldwide. In aquatic ecosystems, algae are important primary producers providing nutrients for a wide range of species, so they play a fundamental role in maintaining the balance of the marine ecosystem. Thus, the toxic effect of pollutants on algae can have a negative impact on organisms at higher trophic levels. The microplastic toxic effect on algae is studied by many researches, leading to many different conclusions due to different experimental designs. The polymer type is an important parameter, as it influences the growth rate, the photosynthetic pigments content, and the oxidative stress. Polystyrene is considered more toxic than other types of microplastics. Studies show that plastics of a smaller size and with a positive surface charge have a higher toxic effect on algae. MNPs toxicity to algae strongly depends on their concentration, and becomes more severe as its level increase. Moreover, size and concentration of plastic particles influence changes in reactive oxygen species and the enzymatic antioxidant activity. MNPs are also a vector for other environmental pollutants. Effects of pollutant-MNPs complexes are more often found to be antagonistic than synergetic, in consequence of toxic substance adsorption on the MNPs surface and their lower bioavailability to algae. The aim of this review was to summarize effects and impacts of microplastics and coexisting pollutants on algal populations, on the basis of currently available literature.


Comparison of FT-NIR transmission and UV-vis spectrophotometry to follow the mixing kinetics and to assay low-dose tablets containing riboflavin.
For several years, near-infrared spectroscopy (NIRS) has become an analytical technique of great interest for the pharmaceutical industry, particularly for the non-destructive analysis of dosage forms. The goal of this study is to show the capacity of this new technique to assay the active ingredient in low-dosage tablets. NIR spectroscopy is a rapid, non-destructive technique and does not need any sample preparation. As an example, a binary mixture of microcrystalline cellulose and riboflavin was used to prepare tablets of different weights by direct compression. A prediction model was built by using a partial least square regression fit method. The NIR assay was performed by transmission. The results obtained by NIR spectroscopy were compared with a conventional UV-vis spectrophotometry method. The study showed that tablets can be individually analysed by NIR with high accuracy. It was shown that the variability of this new technique is less important than that of the conventional method which is the UV-vis spectrophotometry.


Impact of cyadox on human colonic microflora in chemostat models.
The aim of this study was to evaluate the microbiological safety of cyadox, a new member of quinoxaline-1,4-dioxides (QdNOs), on human intestinal flora. Four chemostats containing human fecal flora were exposed to 0, 16, 32, and 128 μg/mL of cyadox, respectively. Bacterial populations, resistance rates of two predominant bacteria and short-chain fatty acids (SCFA) were monitored daily prior to and during drug MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products exposure. Colonization resistance (CR) of each community was determined by three successive daily challenges of Salmonella typhimurium. Efflux pump gene (oqxAB) in the Escherichia coli and Enterococcus strains were analyzed by PCR amplification and DNA sequencing. No change in SCFA was observed after exposure to different concentrations of cyadox. Lower concentration of cyadox (16 μg/mL) had no adverse effect on human microflora. However, higher concentrations of cyadox (32 and 128 μg/mL) could change bacterial population and increase the proportion of resistant E. coli and Enterococcus. More than 26% (12/46) of cyadox resistant E. coli strains contained oqxAB gene, while all the resistant Enterococcus were negative to oqxAB gene. Relationship between the occurrence of oqxAB gene and cyadox exposure is inconclusive. Our data indicated that 16 μg/mL might be the no observed effect concentration (NOEC) of cyadox. Derived microbiological acceptable daily intake (mADI) would be 1552.03 μg/kg d. The data obtained in present study indicated that cyadox was a safe member of QdNOs family of antimicrobial agents.


Innovation and value-driven engineering.
Emerging strategies to simultaneously catalyse rewardable innovation in the field of medical devices and reduce health-care costs could also be applicable in drug development.


The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19.
The global coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on global social and economic development and human health. By combining traditional Chinese medicine (TCM) with modern medicine, the Chinese government has protected public health by supporting all phases of COVID-19 prevention and treatment, including community prevention, clinical treatment, control of disease progression, and promotion of recovery. Modern medicine focuses on viruses, while TCM focuses on differential diagnosis of patterns associated with viral infection of the body and recommends the use of TCM decoctions for differential treatment. This differential diagnosis and treatment approach, with its profoundly empirical nature and holistic view, endows TCM with an accessibility advantage and high application value for dealing with COVID-19. Here, we summarize the advantage of and evidence for TCM use in COVID-19 prevention and treatment to draw attention to the scientific value and accessibility advantage of TCM and to promote the use of TCM in response to public health emergencies. Please cite this article as: Huang M, Liu YY, Xiong K, Yang FW, Jin XY, Wang ZQ, Zhang JH, Zhang BL. The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19. J Integr Med. 2023; 21(5): 407-412.


Biofilm on the pipeline wall is an important transmission route of resistome in drinking water distribution system.
Due to the intensive use of antibiotics, the drinking water distribution system (DWDS) has become one of the hotspots of antibiotic resistance. However, little is known about the role of biofilm in the aspect of spreading resistance in DWDS. In present study, four lab-scale biological annular reactors (BAR) were constructed to investigate the transmission of ARGs exposed to a certain amount of antibiotic (sulfamethoxazole) synergistic disinfectants. It was emphasized that pipe wall biofilm was an important way for ARGs to propagate in the pipeline, and the results were quantified by constructing an operational taxonomic unit (OTU) network map. The network analysis results showed the biofilm contribution to waterborne bacteria was finally estimated to be 51.45% and 34.27% in polyethylen (PE) pipe and ductile iron (DI) pipe, respectively. The proportion of vertical gene transfer (VGT) in biofilm was higher than that in water, and the occurrence of this situation had little relationship with the selection of pipe type. Overall, this study revealed how biofilm promoted the transmission of resistome in bulk water, which can provide insights into assessing biofilm-associated risks and optimizing pipe material selection for biofilm control in DWDS.


TriMem: A parallelized hybrid Monte Carlo software for efficient simulations of lipid membranes.
Lipid membranes are integral building blocks of living cells and perform a multitude of biological functions. Currently, molecular simulations of cellular-scale membrane remodeling processes at atomic resolution are extremely difficult, due to their size, complexity, and the large times-scales on which these processes occur. Instead, elastic membrane models are used to simulate membrane shapes and transitions between them and to infer their properties and functions. Unfortunately, an efficiently parallelized open-source simulation code to do so has been lacking. Here, we present TriMem, a parallel hybrid Monte Carlo simulation engine for triangulated lipid membranes. The kernels are efficiently coded in C++ and wrapped with Python for ease-of-use. The parallel implementation of the energy and gradient calculations and of Monte Carlo flip moves of edges in the triangulated membrane enable us to simulate large and highly curved membrane structures. For validation, we reproduce phase diagrams of vesicles with varying surface-to-volume ratios and area difference. We also compute the density of states to verify correct Boltzmann sampling. The software can be used to tackle a range of large-scale membrane remodeling processes as a step toward cell-scale simulations. Additionally, extensive documentation make the software accessible to the broad biophysics and computational cell biology communities.


Changes in renal function and oxidative damage in methamphetamine-treated rat.
In this study, we observed renal damage and peroxidative injury as the acute or sub-acute effect of methamphetamine (MA) to determine whether MA intoxication can be diagnosed from immunohistochemical changes in the kidney. In addition, renal function was investigated in relation to the immunohistochemical changes. A single administration of MA (group I) (50mg/kg/ (i.p.)) and repeated administration (group II) (10mg/kg/day (i.p.) for 5 days) were designed as an acute model and a sub-acute or chronic model. Immunohistochemically, cell damage markers were observed. Then, renal function markers and minerals in blood were measured. Myoglobin and creatinine phosphokinase (CPK) in blood were also analyzed. In group I, ubiquitin immunoreactivity was enhanced only in the renal tubules. Creatinine increased, while K, Ca, and P decreased (P<0.01). CPK increased significantly (P<0.01). Therefore, it was suspected that MA might induce renal dysfunction with renal tubule damage. This damage might be related to leakage of CPK from muscle. In group II, 8-hydroxy-2'-deoxyguanosine (8-OH-dG) increased immunohistochemically and quantitatively (P<0.01). It was considered that oxidative DNA damage might be induced by repeated administration. It was considered that this study offers basic information for the evaluation of pathological changes in the kidney in MA-related autopsy cases.


Trends in death attributed to myocardial infarction, heart failure and pulmonary embolism in Europe and Canada over the last decade.
Worldwide, cardiovascular diseases and cancer account for ∼40% of deaths. Certain reports have shown a progressive decrease in mortality. Our main objective was to assess mortality trends related to myocardial infarction (MI), heart failure (HF) and pulmonary embolism (PE). MI, HF and PE were studied as cause of death based on the analysis of death certificates in Canada (C), England and Wales (E), France (F) and Sweden (S). We also used a multiple cause approach. Age-standardized death rates (SDR) were calculated. The SDR for MI, HF or PE as the underlying cause of death, all decreased during the last decade. The decrease in SDR secondary to MI exceeded that for HF or PE. Concerning multiple cause of death, a greater decrease was also found for MI, compared with HF or PE. We confirm the beneficial trends in SDR with MI, HF or PE both as underlying or multiple causes in the studied countries. For HF and PE, multiple cause approach seems more accurate to describe the burden of these two pathologies. Our study also suggests that more efforts should be dedicated to HF and PE in order to achieve similar trends than in MI.


Animal models for arthritis.
Animal models for rheumatic diseases complement human investigations to study in detail pathogenic hypotheses and therapeutic strategies. An overview of animal studies in the last years shows examples for ideas taken from bench to bedside and from bedside to bench. Depending on the disease studied, progress includes a refinement of physiological and pathogenic thinking and a better definition of promising cellular and molecular therapeutic targets.


Essential radiographic evaluation for distal radius fractures.
Fractures of the distal radius can be complex injuries, often generating multiple fragments with distortion of the normal anatomy in all three dimensions. Superficial assessment of the injury on the standard PA and lateral radiographs often can result in incomplete recognition of the injury pattern and a misdirected approach to treatment. In addition, failure to recognize subtle radiographic findings may result in the acceptance of a reduction that has significant residual incongruency and articular surface disruption. Standard radiographs of the distal radius can provide a wealth of information about the topography of the bone if the surgeon knows what to look for. The ability to recognize detailed landmarks and parameters on the radiographic images and convert this information into a three-dimensional visual image is a skill that requires education and training. As more aggressive treatments have emerged for anatomic restoration of the bony and articular anatomy, accurate identification of the pattern of injury has become essential. Parameters such as the tear drop angle, AP distance, and articular separation have been recognized only recently. Because these parameters reflect the congruency of the articular surface,it would be natural to assume that postreduction films in which these parameters are abnormal would compromise clinical outcome. Because nearly all historical studies do not include routine evaluation of these parameters, knowledge of radiographic correlation with clinical outcome is still incomplete. At the same time, previous studies to assess outcome of distal radius fractures may be compromised by the failure to recognize residual deformity and articular incongruency that would have been evident with measurement of these parameters. With careful understanding of the radiographic landmarks, radiographic parameters, and patterns of injury, the surgeon can visualize a more accurate picture of the fracture itself and the reduction. As a result, treatment decisions for distal radius fractures can be based on a more thorough understanding of the anatomy of the injury, and future grading of radiographic results may reflect more accurately the precision of the articular restoration.


Inhibition by Porphyromonas gingivalis LPS of apoptosis induction in human peripheral blood polymorphonuclear leukocytes.
Many factors, such as cytokines and bacterial products, are known to affect the life-span of polymorphonuclear leukocytes (PMNs). We investigated here whether Porphyromonas gingivalis (P.gingivalis) LPS slows down the apoptotic process of PMNs. During incubation in regular culture medium, the viability of PMNs progressively declined, producing apoptotic cells, characterized by chromatin condensation, internucleosomal DNA fragmentation, cell shrinkage and blebbing of plasma membrane. P.gingivalis LPS significantly increased the viability of PMNs and reduced the production of fragmented DNA, as efficiently as E.coli LPS. The present study suggests that the retardation of PMNs apoptosis by P.gingivalis LPS may modulate the restoration of acute inflammation in the periodontal tissues, where activated PMNs accumulate.


Mechanistic investigation into flow-through electrochemical oxidation of sulfanilamide for groundwater using a graphite anode.
The technical effectiveness/merit of electrochemical oxidation (EO) has been recognized. Nonetheless, its practical application to groundwater remediation has not been fully implemented due to several technical challenges. To overcome the technical incompleteness, this study adopted a graphite anode in the flow-through system and studied the mechanistic roles of a graphite anode. To this end, groundwater contaminated with sulfanilamide was remediated by means of EO, and sulfanilamide oxidation was quantitatively determined in this study. Approximately 60% of sulfanilamide was degraded at the anode zone, and such observation offered that the removal of sulfanilamide was not closely related with current variations (10-100 mA). However, this study delineated that sulfanilamide removal is contingent on the flow speed. For example, the removal of sulfanilamide was lowered from 59 to 25% owing to a short contact time when the flow velocity was increased from 0.14 to 0.55 cm/min. This study also delineated that a shorter anode-cathode distance could offer a favorable chance to enhance the removal of sulfanilamide even under an identical current. A shorter distance could offer a chance to save energy due to the lower voltage operation. This study also offered that chloride (Cl-) and sulfate (SO42-) electrolytes served a crucial role in the generation of active species. In contrast, bicarbonate (HCO3-) and synthetic groundwater electrolytes impeded the oxidation rate because HCO3- scavenged the other active species. In an effort to seek the oxidation mechanisms of a graphite anode, scavenger, cyclic voltammetry test, and electron https://en.wikipedia.org/wiki/Electron_paramagnetic_resonanceparamagnetic resonance (EPR) analysis were done. From a series of the tests, it was inferred that a graphite anode did not directly affect the generation of the active species. Thus, the prevalence of the oxygenated functional groups on an anode surface could be the main mechanism in sulfanilamide removal due to the enhanced electron transfer.


Steel slags for enhanced removal of landfill leachate in a three-dimensional electrochemical oxidation system.
In this study, a three-dimensional electrochemical oxidation system, with steel slags as particle electrodes, was applied to deal with landfill leachate. The characteristics of particle electrodes were investigated by scanning electron microscope (SEM), X-ray fluorescence spectroscopy (XRF) and X-ray diffraction (XRD) measurements. It was found that the steel slag exhibited rough and irregular surface and mainly consisted of SiO2 (Quartz), which indicated the enhanced absorbed and electroconducted abilities. Subsequently, comparative degradation tests between two-dimensional (2D) and three-dimensional (3D) electrochemical oxidation systems were carried out and results indicated removal efficiencies of COD. Moreover, NH4+-N from landfill leachate in 3D system was greatly improved compared with that of 2D system. Besides, operating conditions were also optimized to interelectrode distance of 1 cm, current density of 20 mA·cm-2, initial pH value of 4.4 and steel slag concentration of 0.30 g·mL-1, all of which were determined to guarantee excellent landfill leachate removal efficiency. In addition, a possible removal mechanism for this system was proposed. The introduction of steel slag particle electrodes in three-dimensional electrochemical oxidation system implied the concept for "using waste to treat waste", providing a workable way in pollutant elimination.


Human placental development and function.
The placenta is a transient fetal organ that plays a critical role in the health and wellbeing of both the fetus and its mother. Functionally, the placenta sustains the growth of the fetus as it facilitates delivery of oxygen and nutrients and removal of waste products. Not surprisingly, defective early placental development is the primary cause of common disorders of pregnancy, including recurrent miscarriage, fetal growth restriction, pre-eclampsia and stillbirth. Adverse pregnancy conditions will also affect the life-long health of the fetus via developmental programming[1]. Despite its critical importance in reproductive success and life-long health, our understanding of placental development is not extensive, largely due to ethical limitations to studying early or chronological placental development, lack of long-term in vitro models, or comparative animal models. In this review, we examine current knowledge of early human placental development, discuss the critical role of the maternal endometrium and of the fetal-maternal dialogue in pregnancy success, and we explore the latest models of trophoblast and endometrial stem cells. In addition, we discuss the role of oxygen in placental formation and function, how nutrient delivery is mediated during the periods of histotrophic nutrition (uptake of uterine secretions) and haemotrophic nutrition (exchange between the maternal and fetal circulations), and how placental endocrine function facilitates fetal growth and development.


Applying Proteomics to Investigate Extracellular Matrix in Health and Disease.
The molecular composition of basement membranes (BMs) has traditionally been investigated by candidate-based approaches leading to the identification of key structural components as described in previous chapters. Laminins, collagen IV, nidogens, perlecan, and type XV/XVIII collagen are integral to BMs with isoforms showing tissue specificity. More recently the application of mass spectrometry (MS)-based proteomics has led to the discovery of many more structural and regulatory components of BMs and more broadly, extracellular matrix (ECM). These investigations have revealed tissue-specific signatures of between 100 and 150 ECM components, demonstrating the complexity of the extracellular niche. In addition to providing a structural scaffold for cells, ECM is a dynamic extracellular environment capable of regulating the physical properties of tissues. Global investigations of ECM with proteomics in turn enable systems level analyses and when applied to health and disease states these investigations provide insights into pathways regulating matrix dysregulation. This chapter focuses on the methods used to extract ECM and on the analysis of its composition using MS-based proteomics, and it provides examples of how these approaches have been used to investigate health and disease states.


A universal SARS-CoV DNA vaccine inducing highly cross-reactive neutralizing antibodies and T cells.
New variants in the SARS-CoV-2 pandemic are more contagious (Alpha/Delta), evade neutralizing antibodies (Beta), or both (Omicron). This poses a challenge in vaccine development according to WHO. We designed a more universal SARS-CoV-2 DNA vaccine containing receptor-binding domain loops from the huCoV-19/WH01, the Alpha, and the Beta variants, combined with the membrane and nucleoproteins. The vaccine induced spike antibodies crossreactive between huCoV-19/WH01, Beta, and Delta spike proteins that neutralized huCoV-19/WH01, Beta, Delta, and Omicron virus in vitro. The vaccine primed nucleoprotein-specific T cells, unlike spike-specific T cells, recognized Bat-CoV sequences. The vaccine protected mice carrying the human ACE2 receptor against lethal infection with the SARS-CoV-2 Beta variant. Interestingly, priming of cross-reactive nucleoprotein-specific T cells alone was 60% protective, verifying observations from humans that T cells protect against lethal disease. This SARS-CoV vaccine induces a uniquely broad and functional immunity that adds to currently used vaccines.


Low-velocity, civilian firearm extremity injuries-review and update for radiologists.
Firearm injuries are a preventable epidemic in the USA. Extremities are commonly affected in gunshot injuries. Such injuries may be complex with concomitant osseous, soft tissue, and neurovascular components. The maximum wounding potential of a projectile is determined by its kinetic energy and the proportion of the kinetic energy that is transmitted to the target. Accurate assessment of ballistic injuries is dependent on utilizing the principles of wound ballistics, accurate bullet count, and ballistic trajectory analysis. The goals of this article are to review wound ballistics and the imaging evaluation of extremity civilian firearm injuries in the adult population, with emphasis on ballistic trajectory analysis, specific ballistic fracture patterns, and diffuse, secondary soft tissue ballistic injuries.


Utility of a Structured Teaching Approach, Rehearsal, and Training for Patients With Autism Spectrum Disorder to Avoid Physical Restraint During Induction of Anesthesia.
We aimed to determine whether the use of a structured teaching approach, rehearsing, and training (SRT) for anesthesia induction in patients with autism spectrum disorder (ASD) could reduce the need for physical restraint. Retrospective observational study METHODS: We retrospectively analyzed 63 patients (4 to 40 y old) with ASD who underwent general anesthesia for dental treatment. Patients were divided into SRT (n = 22) and non-SRT (n = 41) groups. In the SRT group, patients were presented with a visual guide based on a structured teaching approach at the pre-anesthetic consultation. The guide comprised photographs of the places, tools, and processes that the patient would experience prior to anesthesia induction. Patients then practiced these processes (rehearsal). Patients in the non-SRT group were administered anesthesia in a conventional manner without SRT. The percentage of patients needing physical restraint was significantly lower in the SRT (3/22, 13%) than in the non-SRT group (21/41, 51%, P < .001). The SRT method reduces the need for physical restraint in patients with ASD during anesthesia induction.


Hydroxychloroquine blood levels predicts flare in childhood-onset lupus nephritis.
Low hydroxychloroquine (HCQ) blood levels are predictors of flare in adult lupus. Childhood-onset systemic lupus erythematosus (cSLE) has high morbidity with renal involvement in up to 80% of cases. The aim of this study is to determine the HCQ cut-off levels which predicts flare in childhood-onset lupus nephritis (LN). Sixty LN patients on HCQ use for at least 6-months were prospectively evaluated at baseline (BL) and about 6-months later for cSLE flare and HCQ blood levels (ng/mL) measured by liquid chromatography-tandem mass spectrometry. There were 19 patients (32%) with flare, during the study with median SLEDAI increase of 4 (0-8). Median (IQR) BL HCQ levels of the flare group were lower compared to stable patients [557.5 (68.6-980.3) vs. 1061.9 (534.8-1590.0 ng/mL); p=0.012]. ROC curve analysis demonstrated that HCQ levels≤1075 ng/mL were associated with a 5.08 (95%CI 1.28-20.13; p=0.021) times increased risk of flare. Six-month HCQ levels revealed that most patients 24/54 (44%) had persistently low levels (≤1075) during follow-up. Among those, 11/24 (46%) had flare. Multiple logistic regression analysis including prednisone use, baseline SLEDAI-2K, adherence based on pharmacy refill and BL HCQ blood levels as possible predictors of flare revealed that only HCQ blood level was independently associated with flare (OR 0.999, 95%CI 0.998-1.0, p=0.013). We demonstrated that HCQ blood cut-off level under 1075 ng/mL predicts flare in childhood-onset LN patients under prescribed HCQ dose of 4.0-5.5 mg/kg/day. We further observed that most of these patients have compliance issues reinforcing the need for a close surveillance particularly in those with levels below the defined cut-off.


A nonisotopic assay method for hepatitis C virus NS5B polymerase.
The RNA-dependent RNA polymerase of hepatitis C virus (HCV) is responsible for replication of genomic RNA. A novel nonisotopic assay method is described for detecting its enzymatic activity. The 5' end of the in vitro-transcribed template RNA was attached covalently to the surface of a Covalink module using carbodiimide condensation. The RNA strand containing the 3' untranslated region (3' UTR) of HCV at its 3' end was free in the solution. A purified NS5B polymerase and NTPs along with biotin-labeled UTP were added to this module and the polymerization activity could be detected colorimetrically with streptavidin-conjugated alkaline phosphatase.


Helicobacter pylori in gastroduodenal diseases: rapid identification by endoscopic brush cytology.
Previous reports showed Helicobacter pylori (H. pylori) in type B gastritis-affected stomachs. This study was carried out to compare H. pylori staining effectiveness on biopsy to brush cytology. Tissue and brush parallel samples of gastric mucosa with abnormal or normal appearances were examined: 57.6% H. pylori-positive pieces from the antrum and 19.2% from the body were found, versus 65.3% and 25% H. pylori-positive brush smears, respectively. H. pylori resembling organisms were mainly related to chronic and acute antral inflammations and were often associated with higher amounts of round-shaped cocco-bacteria. In addition, H. pylori direct stain on brushing is proposed as the most rapid and reliable method for the routine diagnosis of Helicobacter pylori infection, in both ulcer or nonulcer gastritis.


Increased disability and MRI lesions after discontinuation of IFN-beta-1a in secondary progressive MS.
To examine neurological and magnetic resonance imaging (MRI) changes following discontinuation of interferon (IFN)-beta-1a treatment in secondary progressive multiple sclerosis (SPMS). The study involved 21 SPMS patients who received subcutaneous (s.c.) IFN-beta-1a 44 microg three times weekly (t.i.w.) for 12 months and were thereafter followed up without treatment for a further 12 months. The number of relapses, disability on the Expanded Disability Status Scale (EDSS) and MRI were recorded at baseline, at 12 months of IFN-beta-1a 44 microg t.i.w. and 1 year after discontinuation of treatment. During the 12-month treatment EDSS score and volumes of brain T2- and T1-weighted lesions remained without significant progression, but at 12 months after treatment discontinuation both EDSS score and the volumes of cerebral lesions increased significantly. Cerebrospinal fluid fraction increased significantly both during the treatment and during follow-up. Discontinuation of IFN-beta-1a 44 microg t.i.w. in SPMS may be associated with an increase in neurological disability and brain lesions on MRI.


Urinary incontinence in women 55 years and older: A scoping review to understand prevalence, incidence, and mortality of urinary incontinence during secondary care admission.
Up to 40% of older women living in the community experience urinary incontinence. In community settings, urinary incontinence impacts the quality of life, morbidity, and mortality rates. However, little is known about urinary incontinence and its impact on older women admitted to hospitals. This scoping review aims to establish the current knowledge of urinary incontinence during hospital admission for women (⩾ 55 years of age) with three key objectives: (a) What is the prevalence/incidence of urinary incontinence? (b) What health conditions are associated with urinary incontinence? (c) Is there an association between urinary incontinence and mortality? Empirical studies were included in assessing the incidence/prevalence of urinary incontinence during hospital admissions and its related morbidities and mortality rates. Studies which only included men or younger women (< 55 years of age) were excluded. Only articles written in English and conducted between 2015 and 2021 were included. A search strategy was developed, and CINAHL, MEDLINE, and Cochrane databases were searched. Data from each article meeting the criteria were pulled into a table, including study design, study population, and setting, aims, methods, outcome measures, and significant findings. A second researcher then reviewed the populated data extraction table. Overall, 383 papers were found: 7 met inclusion/exclusion criteria. Prevalence rates ranged from 22% to 80% depending on the study cohort. Several conditions were associated with urinary incontinence, including frailty, orthopaedics, stroke, palliative care, neurology, and cardiology. There was a potential positive association between mortality and urinary incontinence, although only two papers reviewed reported mortality. A dearth of literature determined the prevalence, incidence, and mortality rates for older women admitted to hospitals. Limited consensus on associated conditions was found. Further research is needed to fully explore urinary incontinence in older women during hospital admissions, particularly concerning prevalence/incidence and its association with mortality.


Determination of alpha-1-antitrypsin phenotypes and M subtypes by isoelectric focusing in immobilized pH gradients.
A procedure to determine alpha-1-antitrypsin phenotypes (Pi types), including the six common PiM subtypes, is described. Phenotypes of the inhibitor, including the deficiency phenotype PiZ and the PiM subtypes, can be identified by isoelectric focusing in an immobilized pH gradient with a pH range of 4.2 to 5.0 or 4.0 to 5.0. This method gives clear separation of M, S, V, P and Z allele products. Up to 24 samples can be analyzed in a single overnight run using commercially available equipment and reagents.


Determination of selenium in biological samples by gas-liquid chromatography with electron-capture detection.
Selenium can be determined quantitatively in biological samples after nitric acid-magnesium nitrate digestion and formation of 5-nitropiazselenole, by extraction into toluene for gas-liquid chromatography with electron-capture detection. The method is suitable for the determination of selenium in orchard leaves, bovine liver and human placenta, hair, blood and urine.


Behavioural and physiological responses of Gammarus fossarum (Crustacea Amphipoda) exposed to silver.
The study aims at investigating the effects of silver (Ag), a re-emerging contaminant, on physiological and behavioural responses in Gammarus fossarum. In a first experiment, G. fossarum Ag LC50s were evaluated during 96 h under semi-static mode of exposure. Juveniles appeared to be more sensitive to Ag (LC5096h: 1.01 μg L(-1)) than ovigerous females (LC5096h: 1.9 μg L(-1)) and adult males (LC5096h: 2.2 μg L(-1)). In a second experiment, the physiological (osmo-/ionoregulation; antioxidant enzymes; lipid peroxidation (LPO)) and behavioural (locomotor activity and ventilation) responses of male G. fossarum exposed to Ag (0, 0.5, 1, 2, and 4 μg L(-1)) were investigated. The mortality and Ag bioconcentration of gammarids exposed to Ag were significantly higher than controls. Concerning physiological responses, a 48 h-exposure to Ag had no impact on catalase activity but led to a significant decrease of haemolymph osmolality and [Na(+)]. On the contrary, LPO, Se-GPx and Na(+)/K(+)-ATPase activity were significantly increased. Behavioural responses, such as locomotor and ventilatory activities, were also significantly reduced in Ag exposed gammarids. After 96 h-exposure, especially to 0.5 μg Ag L(-1), most responses (ventilation, locomotor activity, haemolymph osmolality and [Na(+)]) were even more pronounced and haemolymph [Cl(-)] was significantly decreased but, contrary to observations after 48 h-exposure, Na(+)/K(+)-ATPase activity was significantly reduced. Our results demonstrate the drastic effects of realistic [Ag] concentration (0.5 μg Ag L(-1)) on an ubiquitous and functionally important freshwater invertebrate (implied in detritus breakdown), but also strongly suggest an energetic reallocation to the detriment of locomotor activity and in favour of maintenance functions (i.e., osmoregulation and detoxification). These results highlight the risk represented by Ag and the need to perform integrated studies (at different scales, from individual to ecosystem).


Internalization of Calcium Oxalate Calculi Developed in Narrow Cavities.
We describe the case of a patient with calcium oxalate monohydrate and calcium oxalate dihydrate calculi occluded in cavities. All those calculi were located inside narrow cavities covered with a thin epithelium that permits their visualization. Urinary biochemical analysis showed high calciuria, not hypercalciuria, hypocitraturia, and a ratio [calcium]/[citrate] >0.33. The existence of cavities of very low urodynamic efficacy was decisive in the formation of such calculi. It is important to emphasize that we observed a thin epithelium covering such cavities, demonstrating that this epithelium may be formed after the development of the calculi through a re-epithelialization process.


Identification of the structural gene for glyoxalase I from Saccharomyces cerevisiae.
The structural gene for glyoxalase I (GLO1) of Saccharomyces cerevisiae was identified. The GLO1 gene contained an open reading frame with 326 amino acids, and the molecular weight of the gene product (Glo1p) deduced from the DNA sequence was calculated to be 37,207.06. Glyoxalase I activity increased approximately 95-fold when the GLO1 gene was introduced into the yeast cell with a multicopy plasmid, and the resultant transformant showed the increased resistance against methylglyoxal. Since the knockout mutant of the GLO1 gene of haploid strain of S. cerevisiae was still viable, the GLO1 gene was thought to be unnecessary for growth of the yeast. The GLO1 gene was overexpressed in two kinds of glutathione-deficient mutants, gamma-glutamylcysteine synthetase-deficient (gsh1(-)) and glutathione synthetase-deficient (gsh2(-)), respectively, and the sensitivites to methylglyoxal were compared. The gsh1-deficient mutant, which could not produce glutathione at all, was hypersensitive to methylglyoxal, and overproduction of the Glo1p did not restore the growth arrest caused by exogenously added methylglyoxal. The gsh2-deficient mutant, which accumulates gamma-glutamylcysteine (an intermediate of glutathione biosynthesis), was also sensitive to methylglyoxal compared with the isogenic wild type strain, although the growth arrest caused by methylglyoxal was partially restored by overexpression of the GLO1 gene. Purified glyoxalase I from yeast could use gamma-glutamylcysteine as a substrate (kcat/Km = 1.89 x 10(7) M-1 s-1, glutathione; 3.47 x 10(4) M-1 s-1, gamma-glutamylcysteine).


Degron Tagging Using mAID and SMASh Tags in RPE-1 Cells.
Degron tags allow the precise and well-controlled analysis of essential genes by rapidly inducing degradation of the protein of interest. This is critical when the consequences of loss of gene function needs to be analyzed in a strictly defined time window such as a specific cell cycle phase. We have recently published the successful application of degron tags to analyze cell cycle genes such as CDC6, CCNA2, and CCNB1. A critical aspect of our approach was to combine two tags to generate a synergy in the degradation dynamics. Here we outline our approach and describe some of the essential steps to generate double-degron-tagged genes in RPE-1 cells. Similar procedures can easily be applied to other cell lines.


Steroidal saponins from the flowers of Dioscorea bulbifera var. sativa.
Eleven steroidal saponins, dioscoreanosides A-K, along with five known congeners, were isolated from the flowers of Dioscorea bulbifera var. sativa. Their structures were established by extensive NMR experiments in conjunction with mass spectrometry. The isolated compounds were tested for cytotoxicity against urinary bladder carcinoma cells (ECV-304 cells). Our results revealed a moderate activity for spiroconazol A (15), pennogenin 3-O-α-l-rhamnopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→4)-[α-l-rhamnopyranosyl-(1→2)]-β-d-glucopyranoside (12), and 26-O-ß-d-glucopyranosyl-(25R)-5-en-furost-3ß,17α,22α,26-tetraol-3-O-α-l-rhamnopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→4)-[α-l-rhamnopyranosyl-(1→2)]-β-d-glucopyranoside (13).


Converting organosulfur compounds to inorganic polysulfides against resistant bacterial infections.
The use of natural substance to ward off microbial infections has a long history. However, the large-scale production of natural extracts often reduces antibacterial potency, thus limiting practical applications. Here we present a strategy for converting natural organosulfur compounds into nano-iron sulfides that exhibit enhanced antibacterial activity. We show that compared to garlic-derived organosulfur compounds nano-iron sulfides exhibit an over 500-fold increase in antibacterial efficacy to kill several pathogenic and drug-resistant bacteria. Furthermore, our analysis reveals that hydrogen polysulfanes released from nano-iron sulfides possess potent bactericidal activity and the release of polysulfanes can be accelerated by the enzyme-like activity of nano-iron sulfides. Finally, we demonstrate that topical applications of nano-iron sulfides can effectively disrupt pathogenic biofilms on human teeth and accelerate infected-wound healing. Together, our approach to convert organosulfur compounds into inorganic polysulfides potentially provides an antibacterial alternative to combat bacterial infections.


Expression of cyclin D1 and Ki-67 in squamous cell carcinoma of the oral cavity: clinicopathological and prognostic significance.
The prognostic and clinicopathologic significance of cyclin D1 and Ki-67 expressions was studied in oral squamous cell carcinomas. We performed an immunohistochemical study to determine the level of expression of cyclin D1 and Ki-67 labelling index in tumor specimens obtained from 35 patients, of whom 14 died as a result of recurrent disease, and 20 were free of recurrence at the end of the follow-up period. Overexpression of cyclin D1 was significantly associated with regional lymph node metastases (P=0.00005) and advanced tumor stage (P=0.0007). The relative risk for nodal metastases in the cases that overexpressed cyclin D1 was 2.6. The Ki-67 labelling index was significantly (P=0.001) higher in tumors with poor histologic grade of differentiation. Our results showed that cyclin D1 is a useful prognostic factor, and suggested it could be a marker to help determine the appropriate treatment for patients with oral squamous cell carcinoma. Cyclin D1 and Ki-67 overexpression were positively correlated.


Utilizing constructivism learning theory in collaborative testing as a creative strategy to promote essential nursing skills.
In nursing education, students participate in individual learner testing. This process follows the instructionist learning theory of a system model. However, in the practice of nursing, success depends upon collaboration with numerous people in different capacities, critical thinking, clinical reasoning, and the ability to communicate with others. Research has shown that collaborative testing, a constructivism learning activity and a form of collaborative learning, enhances students' abilities to master these areas. Collaborative testing is a clear, creative strategy which constructivists would say supports the socio-linguistic base of their learning theory. The test becomes an active implementation of peer-mediated learning where individual knowledge is enhanced through problem solving or defense of an individual position with the collaborative method. There is criticism for the testing method's potential of grade inflation and for students to receive grade benefits with little effort. After a review of various collaborative testing methods, this nursing faculty implemented a collaborative testing format that addresses both the positive and negative aspects of the process.


Fengycin induces ion channels in lipid bilayers mimicking target fungal cell membranes.
The one-sided addition of fengycin (FE) to planar lipid bilayers mimicking target fungal cell membranes up to 0.1 to 0.5 μM in the membrane bathing solution leads to the formation of well-defined and well-reproducible single-ion channels of various conductances in the picosiemens range. FE channels were characterized by asymmetric conductance-voltage characteristic. Membranes treated with FE showed nonideal cationic selectivity in potassium chloride bathing solutions. The membrane conductance induced by FE increased with the second power of the lipopeptide aqueous concentration, suggesting that at least FE dimers are involved in the formation of conductive subunits. The pore formation ability of FE was not distinctly affected by the molecular shape of membrane lipids but strongly depended on the presence of negatively charged species in the bilayer. FE channels were characterized by weakly pronounced voltage gating. Small molecules known to modify the transmembrane distribution of electrical potential and the lateral pressure profile were used to modulate the channel-forming activity of FE. The observed effects of membrane modifiers were attributed to changes in lipid packing and lipopeptide oligomerization in the membrane.


DAX1 regulatory networks unveil conserved and potentially new functions.
DAX1 is an orphan nuclear receptor with actions in mammalian sex determination, regulation of steroidogenesis, embryonic development and neural differentiation. Conserved patterns of DAX1 gene expression from mammals to fish have been taken to suggest conserved function. In the present study, the European sea bass, Dicentrarchus labrax, DAX1 promoter was isolated and its conserved features compared to other fish and mammalian DAX1 promoters in order to derive common regulators and functional gene networks. Fish and mammalian DAX1 promoters share common sets of transcription factor frameworks which were also present in the promoter region of another 127 genes. Pathway analysis clustered these into candidate gene networks associated with the fish and mammalian DAX1. The networks identified are concordant with described functions for DAX1 in embryogenesis, regulation of transcription, endocrine development and steroid production. Novel candidate gene network partners were also identified, which implicate DAX1 in ion homeostasis and transport, lipid transport and skeletal development. Experimental evidence is provided supporting roles for DAX1 in steroid signalling and osmoregulation in fish. These results highlight the usefulness of the in silico comparative approach to analyse gene regulation for hypothesis generation. Conserved promoter architecture can be used also to predict potentially new gene functions. The approach reported can be applied to genes from model and non-model species.


Structures of the Human SPAK and OSR1 Conserved C-Terminal (CCT) Domains.
STE20/SPS1-related proline/alanine-rich kinase (SPAK) and oxidative stress responsive 1 (OSR1) kinase are two serine/threonine protein kinases that regulate the function of ion co-transporters through phosphorylation. The highly conserved C-terminal (CCT) domains of SPAK and OSR1 bind to RFx[V/I] peptide sequences from their upstream 'With No Lysine Kinases (WNKs), facilitating their activation via phosphorylation. Thus, the inhibition of SPAK and OSR1 binding, via their CCT domains, to WNK kinases is a plausible strategy for inhibiting SPAK and OSR1 kinases. To facilitate structure-guided drug design of such inhibitors, we expressed and purified human SPAK and OSR1 CCT domains and solved their crystal structures. Interestingly, these crystal structures show a highly conserved primary pocket adjacent to a flexible secondary pocket. We also employed a biophysical strategy and determined the affinity of SPAK and OSR1 CCT domains to short peptides derived from WNK4 and NKCC1. Together, this work provides a platform that facilitates the design of CCT domain specific small molecule binders that inhibit SPAK- and OSR1-activation by WNK kinases, and these could be useful in treating hypertension and ischemic stroke.


Toxicity and physiological interruptions of a proteinaceous toxin from Metarhizium anisopliae against the olive fruit pest, Bacterocera oleae (Diptera: Tephritidae).
The use of natural bioactive compounds mainly proteinaceous secondary metabolites of fungi is one of the promising pest control methods because of their lethal effects on insects in low concentration, limited persistence in environment and easily decomposition into environmentally safe compounds. The olive fruit fly, Bactrocera oleae (Rossi) (Diptera: Tephritidae), is a destructive pest of olive fruits around the world. In the current study, the proteinaceous compounds were extracted from the two isolates (MASA and MAAI) of Metarhizium anisopliae and their effects were evaluated on toxicity, feeding performance and antioxidant system of the adult's olive flies. Both extracts from MASA and MAAI showed entomotoxicity against the adults by 2.47 and 2.38 mg/mL as LC50 concentrations. Also, LT50 values were recorded 1.15 and 1.31 days for MASA and MAAI, respectively. No statistical differences were recorded in the consumption rate of the adults on control and secondary metabolite contained protein hydrolysate. In contrast, the adults fed on LC30 and LC50 concentrations of MASA and MAAI demonstrated significant reduction in the activities of digestive alpha-amylase, glucosidases, lipase, trypsin, chymotrypsin, elastase, amino- and carboxypeptidases. Activity of antioxidant enzymes changed in the adults of B. oleae fed on the fungal secondary metabolites. Catalase, Peroxidase and Superoxide dismutase elevated in the treated adults with the highest amounts of MAAI. Similar results were found in activity of ascorbate peroxidase and glucose-6-phosphate dehydrogenase except for malondialdehyde amount in which no statistical differences were recorded between treatments and control. Relative gene expression of caspase enzymes revealed the higher expression in the treated B. oleae compared to control with the highest level of caspase 8 for MASA and caspases 1 and 8 for MAAI. Results of our study showed that the secondary metabolites extracted from the two isolates of M. anisopliae caused mortality, interrupted digestion and induced oxidative stress in the adults of B. oleae.


Effect of gait retraining for reducing ambulatory knee load on trunk biomechanics and trunk muscle activity.
The purpose of this study was to test the hypothesis that walking with increased medio-lateral trunk sway is associated with lower external knee adduction moment and lower extremity muscle activation, and higher external ipsilateral trunk moment and trunk muscle activity than walking with normal trunk sway in healthy participants. Fifteen participants performed walking trials with normal and increased medio-lateral trunk sway. Maximum trunk sway, first maximum knee adduction moment, lateral trunk bending moment, and bilateral vastus medialis, vastus lateralis, gluteus medius, rectus abdominis, external oblique and erector spinae muscle activity were computed. Walking with increased trunk sway was associated with lower maximum knee adduction moment (95% confidence interval (CI): 0.50-0.62Nm/kg vs. 0.62-0.76Nm/kg; P<.001) and ipsilateral gluteus medius (-17%; P=.014) and erector spinae muscle activity (-24%; P=.004) and greater maximum lateral trunk bending moment (+34%; P<.001) and contralateral external oblique muscle activity (+60%; P=.009). In all participants, maximum knee adduction moment was negatively correlated and maximum trunk moment was positively correlated with maximum trunk sway. The results of this study suggest that walking with increased trunk sway not only reduces the external knee adduction moment but also alters and possibly increases the load on the trunk. Hence, load-altering biomechanical interventions should always be evaluated not only regarding their effects on the index joint but on other load-bearing joints such as the spine.


Pericardial rupture following blunt trauma. Case report and review of the literature.
A case of pericardial rupture following blunt thoracic trauma is presented, together with a collective review of the literature. The rising survival rate is due to heightened awareness of this injury, which should be suspected in all patients who have sustained high-energy trauma.


Attitudes of internal medicine residents regarding influenza vaccination.
To survey the attitudes of internal medicine residents regarding the influenza vaccine and their reasons for accepting or refusing the vaccine during a hospitalwide immunization campaign. Internal medicine residents responded to a written survey. A university-owned, 891-bed, tertiary referral hospital and a 278-bed Veterans Administration hospital in Iowa. Immediately following the immunization campaign, 51% of residents had received the vaccine. Of those residents who were not vaccinated, 42% never had time to go to the vaccine clinic, but only 8% worried about side effects of the vaccine. Residents whose clinics were staffed by infectious disease subspecialists were significantly more likely to be vaccinated (odds ratio = 2.55; CI95 = 1.01 to 6.42) than residents working with general internists or other subspecialists. Knowledge, vaccine availability, and social pressure all increase the likelihood that residents will be vaccinated. Faculty, particularly those interested in infectious diseases, may influence residents to accept the vaccine.


A Single Proximal Interlocking Bolt May Be Sufficient for Retrograde Nailing of Extra-articular Femur Fractures.
To evaluate whether a single proximal interlocking bolt was sufficient during the treatment of extra-articular femur fractures with retrograde medullary nailing. Retrospective comparative study. Academic Level 1 trauma center. The study included 136 patients with extra-articular femur fractures treated with retrograde medullary nailing who met inclusion and follow-up criteria. The intervention included surgical treatment for a femur fracture with retrograde medullary nailing, with comparisons made between those treated with a single proximal interlocking (1 IL) bolt and those treated with 2 proximal interlocking bolts (2 IL). The main outcome measurements were as follows: (1) rate of nonunion and (2) rate of catastrophic implant failure. There was no difference in the rate of nonunion requiring surgical intervention between the 2 groups. There were no catastrophic failures in either group. A single proximal interlocking bolt may be sufficient when using retrograde nailing for the treatment of extra-articular femur fractures. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Confirmation of peak assignments in capillary electrophoresis using immunoprecipitation. Application to D-aspartate measurements in neurons.
Capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection is a powerful tool for analysis of samples ranging from tissue extracts to single cells. However, accurate peak identification in electropherograms is challenging when complex biological samples are analyzed, as often matching a migration time between an analyte and corresponding standard may be insufficient to confirm the peak's identity. A method which combines single-step immunoprecipitation and CE-LIF analysis for investigation of the chiral amino acids in single cells and small tissue samples is demonstrated. D-Aspartate (D-Asp) has been reported in the central nervous system of the invertebrate neurobiological model Aplysia californica. In order to confirm the identity of D-Asp signal in the complex electropherograms of nerve tissue extracts and individual neurons, anti-D-Asp serum, preincubated with L-Asp conjugate, is added to the sample. This selectively binds the free D-Asp, creating an antibody-antigen complex with a migration time similar to that of antibody alone, but not that of D-Asp. The complete disappearance of the putative D-Asp peak confirms its identity and validates that there are no other detectable analytes co-migrating with D-Asp in the electropherogram.


Do lung volumes change with sleep state in the neonate?
We have studied 12 healthy full-term babies, mean age 3.2 days, using physiological criteria--EEG, electrooculogram, electromyogram, respiratory regularity and visible movement--to assess sleep state, and a respiratory jacket to record changes in functional residual capacity (FRC). A total of 593 min of sleep data were analysed. Of the recordings, 39% were scored as quiet sleep, 40% as active and 21% as indeterminate sleep. The mean maximum variation in FRC overall was 29 ml (SD +/- 15.4 ml). Examination of these figures showed that FRC variations during sleep state changes were smaller than those seen within a defined sleep state. We conclude that changes in sleep state are not associated with variations in FRC.


Rat intestinal glycolipids. III. Fatty acids and long chain bases of glycolipids from villus and crypt cells.
Previous studies from this laboratory have demonstrated a striking difference in rat intestinal glycolipids between differentiated villus cells and immature crypt cells. Villus cells contained proportionally greater amounts of glucosylceramide and hematoside while crypt cells were deficient in hematoside, but contained proportionally greater amounts of trihexosylceramide. In order to further elucidate possible differences between villus and crypt cell glycolipids, a study of the sphingosine and fatty acids of rat intestinal glycolipids was conducted. Villus and crypt cells were separated from rat intestine and the glycolipids purified. Fatty acids and long chain bases of the three major glycolipids (glucosylceramide, trihexosylceramide, hematoside) extracted from these cells were characterized. Phytosphingosine accounted for 63-73% of the total long chain bases in all glycolipids whether from villus or crypt cells. Hydroxy fatty acids represented 70% of total fatty acids in the glucosylceramide and in the hematoside but accounted for only 30% in the trihexosylceramide. In addition, trihexosylceramide contained a larger percentage of fatty acids with 20-carbon atoms than glucosylceramide and hematoside isolated from villus cells. These fatty acids were more concentrated in crypt cells than in villus cells glycolipids. These results suggest that hematoside and trihexosylceramide, respectively abundant in villus and in crypt cells, may be derived from a different lactosylceramide precursor and further underscore differences in villus and crypt cell glycolipid synthesis.


College men's and women's respective perceptions of risk to perpetrate or experience sexual assault: the role of alcohol use and expectancies.
The present study examines alcohol use, expectancies (i.e., beliefs about the outcomes of alcohol consumption), and college men's (n = 127) and women's (n = 191) respective perceptions of risk to perpetrate/experience sexual violence. Interactions between alcohol consumption and expectancies were examined. Alcohol expectancies regarding assertiveness increased women's perceived risk for sexual intercourse via alcohol/drugs. Among women reporting high alcohol use, global expectancies were positively associated with perceived risk for sexual intercourse via alcohol/drugs. Furthermore, among women reporting low alcohol use, expectancies regarding assertiveness were positively associated with perceived risk for coerced sexual contact. Implications are discussed.


Photoconductivity of synthetic dopa-melanin polymer.
The photoconductivity effect in synthetic dopa-melanin polymer with relation to the charge hopping conduction has been investigated. Measurements of the rise and decay of photocurrents upon visible radiation (400-800 nm) and at temperatures of 293-326 K allowed the determination of the major trapping levels as follows: 56, 35 and 26 kJ/mol. Spectral response of the steady-state photocurrent in the range 367-1100 nm showed significant departures from the absorption spectrum of melanin. The high concentration of traps or recombination centers can explain the long time-constants calculated from the photocurrent rise and decay curves. The results obtained can support the postulated earlier polarons and hopping model of conductivity in synthetic dopa-melanin.


Exploring reasons for bed pressures in Winnipeg acute care hospitals.
Hospital overcrowding has plagued Winnipeg and other Canadian cities for years. This study explored factors related to overcrowding. Hospital files were used to examine patterns of hospital use from fiscal years 1996/1997 to 1999/2000. Chart reviews were conducted to examine appropriateness of admissions and hospital stays during one pressure week. Results indicate that pressure periods in the hospital system were driven by an influx of older adults with influenza-associated respiratory illnesses. Moreover, examination of one specific pressure week showed that at least 100 beds were occupied by patients who likely did not require acute care. The chart review revealed that a substantial proportion of non-acute patient-days were spent awaiting home care, long-term care, or diagnostic testing services. These findings suggest future bed pressures might be prevented through influenza vaccination and an increase in the availability of--and timely transfer to--alternative levels of care.


Partial hepatic grafting: porcine study on critical volume reduction.
The safe limit of volume reduction in partial hepatic transplantation, including extracorporeal hepatic resection, remains to be clarified. This study evaluated such a limit and pathologic features associated with transplantation of a less than critical volume. Partial hepatic grafting was performed in a porcine orthotopic autotransplantation model. According to the remnant liver volume, animals were classified into three groups: group 1, 73.8% +/- 4.2% (SD); group 2, 52.6% +/- 6.7%; and group 3, 29.4% +/- 6.7% of the whole liver (n = 5 each). Three-day survival was achieved in five (100%), four (80%), and zero animals, respectively. All animals in group 3 died of graft nonfunction; their intraoperative clearance of the total bile acids was significantly worse than the other groups (p < 0.01). After operation the clearance of the total bile acids and hyaluronic acid, which is selectively cleared by hepatic endothelial cells, was significantly better in group 1 than group 2 (p < 0.01 and < 0.05, respectively). On histologic examination postperfusion biopsy specimens of group 3 exhibited severe ischemic changes and portosinusoidal hyperemia, whereas that of groups 1 and 2 exhibited only mild ischemic damages. Transplantation of less than 30% of expected full liver volume could lead to primary graft nonfunction after partial hepatic grafting.


The noncanonical chronicles: Emerging roles of sphingolipid structural variants.
Sphingolipids (SPs) are structurally diverse and represent one of the most quantitatively abundant classes of lipids in mammalian cells. In addition to their structural roles, many SP species are known to be bioactive mediators of essential cellular processes. Historically, studies have focused on SP species that contain the canonical 18‑carbon, mono-unsaturated sphingoid backbone. However, increasingly sensitive analytical technologies, driven by advances in mass spectrometry, have facilitated the identification of previously under-appreciated, molecularly distinct SP species. Many of these less abundant species contain noncanonical backbones. Interestingly, a growing number of studies have identified clinical associations between these noncanonical SPs and disease, suggesting that there is functional significance to the alteration of SP backbone structure. For example, associations have been found between SP chain length and cardiovascular disease, pain, diabetes, and dementia. This review will provide an overview of the processes that are known to regulate noncanonical SP accumulation, describe the clinical correlations reported for these molecules, and review the experimental evidence for the potential functional implications of their dysregulation. It is likely that further scrutiny of noncanonical SPs may provide new insight into pathophysiological processes, serve as useful biomarkers for disease, and lead to the design of novel therapeutic strategies.


Natural levels of lead, cadmium and mercury in tissues and hair of newborn calves from different areas of Czechoslovakia.
Liver, kidney, muscle and hair samples from newborn, born-dead or found-dead calves were collected within 10 days after parturition, for the determination of Pb, Cd and Hg levels. Differential pulse anodic stripping voltammetry at the static mercury dropping electrode was used for Pb and Cd determination after dry ashing of the samples. Cold-vapour atomic absorption spectrometry was used for direct Hg determination. The aim of the study was to monitor background Pb, Cd and Hg levels in vital and important tissues of newborn calves in which nutritional influence was negligible. Three geographic areas in Czechoslovakia were monitored (A, B and C). The following ranges of mean values for all animals were obtained (mg kg-1, wet wt): Pb--muscle (0.04-0.25), liver (0.10-0.29), kidney (0.05-0.43), hair (0.11-0.55); Cd--muscle (0.007-0.038), liver (0.008-0.073), kidney (0.007-0.062), hair (0.009-0.074); Hg--muscle (0.002-0.071), liver (0.005-0.18), kidney (0.004-0.50), hair (0.07-0.77). The value obtained for heavy-metal levels (Pb, Cd, Hg) indicated that there is a significant difference between the groups of found-dead and slaughtered calves from the Nymburk region (muscle--Pb, Cd; liver--Pb; kidney--Pb, Cd). Unexplained high Hg levels in hair samples were measured in the Hradec Králové region.


The extent of local tumor invasion predicts prognosis in stage IE nasal natural killer/T-cell lymphoma: a novel T staging system for risk stratification.
A heterogeneous treatment response and prognosis exists among patients with Ann Arbor stage IE natural killer/T-cell lymphoma (NKTCL), and further risk stratification is required to identify high-risk patients. Here, we assessed the extent of local tumor invasion (LTI) in 185 patients with Ann Arbor stage IE primary nasal NKTCL and proposed a novel four-level T staging system. We found that a more advanced T stage was associated with a significantly lower rate of complete remission (CR) after chemotherapy and a marginally lower rate of CR after radiotherapy. While patients with no LTI (T1) or mild LTI (T2) presented with similar 5-year overall survival (OS; 83.6 % vs. 86.0 %, P = 0.990), those with moderately or highly advanced local disease (T3 or T4) had significantly worse survival (5-year OS was 63.3 % and 35.1 %, respectively). A more advanced T stage (T3 or T4) was an independent prognostic factor for both OS and progression-free survival (PFS) in the Cox regression model. In addition, patients with T3 or T4 disease experienced locoregional failure more frequently than those with T1 or T2 disease, and patients with T4 disease had a significantly higher risk of distant failure. Our data demonstrated that the T staging system, based on the extent of LTI, could serve as an effective clinical parameter for further risk stratification among patients with primary nasal Ann Arbor stage IE NKTCL.


An optimization framework for COVID-19 vaccine allocation and inventory management: A case study.
As the novel coronavirus pandemic wreaked havoc globally, governments have implemented massive vaccination programs to tackle it. However, since the pandemic's emergence moves beyond the second year, some issues have stymied vaccination programs, including vaccine hesitancy, vaccine distribution inequality, new strains of the virus, and a possibility that the virus enters a stage of a requirement for cyclical vaccination. These challenges highlight the need for an appropriate mass COVID-19 vaccination program. Therefore, we attempt to address this problem by developing a bi-objective integrated vaccine allocation and inventory management framework. The goal is to minimize the system costs while maximizing the vaccination service level. Several important factors, such as multiple types of vaccines, the vaccines' perishability concept, demand uncertainty, and motivational strategy, have been addressed using dynamic planning. Besides that, the model development mechanism is carried out to be compatible and applicable to the current general vaccination program policies, forcing few strategic changes. Then, a case study concerning the vaccination program of the city of Mashhad in Iran is applied to the model. The results demonstrated significant advantages in total cost, vaccine shortage, and wastage compared to the current policy. Finally, the Lagrangian relaxation method is implemented on the model to strengthen further its capacity to handle larger-scale problems.


Error in measurement of intraocular pressure with the Icare and IcarePRO.
We sought to determine whether changes in the measurement angle of the Icare TA01i and IcarePRO tonometers led to errors in the measurement of intraocular pressure (IOP). In this prospective, single-facility study, we analyzed 77 patients from November 2017 to September 2019. We measured IOP with the Icare TA01i and IcarePRO while changing the angle of the device with the cornea center and analyzed the associated changes in the measurement. IOP measured with the Icare tilted - 30°, - 15° vertically was significantly higher than that measured with the Icare tilted horizontally (p < 0.0001, p < 0.0001). The IOP measured with a + 10° vertical tilt was significantly lower than that measured horizontally (p < 0.0001). When the IcarePRO was tilted + 90° vertically, the IOP was significantly lower with the patient in the supine position than in the lateral position (p = 0.00058). IOP measured with the Icare and IcarePRO is affected by the measurement angle. The study results will direct the clinicians to exercise extra precautions in determining the measurement angle while measuring IOP.


A case of choroid plexus papilloma with stromal sclerosis and indistinct papillary structures.
We present a case of choroid plexus papilloma with unusual histopathological findings. A 41-year-old Japanese man presented with dizziness. Brain magnetic resonance imaging scan showed a distinct mass in the fourth ventricle. Histopathological examination showed proliferation of cuboidal cells forming irregular trabeculae, small nests, and pseudoglandular and indistinct papillary structures, accompanied by a variable degree of stromal sclerosis. The tissue sections also showed rare mitotic activity, no hypercellularity, cellular pleomorphism, or necrosis. The immunohistochemical findings were tumor cells positive for cytokeratin 7, vimentin, S-100 protein, and transthyretin but negative for cytokeratin 20, BerEP4 and carcinoembryonic antigen. These findings were consistent with choroid plexus papilloma. The combination of these immunohistochemical markers was helpful in establishing the diagnosis, although the morphological finding of stromal sclerosis is rare for choroid plexus papilloma.


Inhibition of Na(+),K(+)-ATPase by the extract of Stephania cephararantha HAYATA and bisbenzylisoquinoline alkaloid cycleanine, a major constituent.
The Stephania cephararantha HAYATA extract, and its constituent bisbenzylisoquinoline alkaloids, such as cycleanine, cepharanthine, isotetrandrine, berbamine, homoaromoline, and cepharanoline were studied for effects on Na(+),K(+)-ATPase activity. The S. cephararantha HAYATA extract inhibited Na(+),K(+)-ATPase activity with an apparent IC(50) value of 540 microg/mL. Cycleanine markedly inhibited Na(+),K(+)-ATPase activity with an IC(50) value of 6.2 x 10(-4)M. It slightly inhibited Mg(2+)-ATPase, H(+)-ATPase, and Ca(2+)-ATPase. No effects on alkaline and acid phosphatase activities were observed. The inhibition by isotetrandrine, homoaromoline, cepharanthine, and berbamine was less marked, and cepharanoline showed no effect. Five synthetic analogues of cepharanthine slightly inhibited the activity. The mechanism of inhibition by cycleanine on Na(+),K(+)-ATPase activity was examined in detail, and the following results were obtained in the overall reaction: (1) the mode of inhibition was noncompetitive with respect to ATP; (2) the degree of inhibition was decreased with a decrease of K(+) concentration; (3) it was not affected by Na(+) concentration; (4) the inhibition mechanism was different from that of ouabain. The activity of K(+)-dependent p-nitrophenyl phosphatase, a partial reaction of Na(+),K(+)-ATPase, did not appear to have been inhibited by cycleanine in the reaction mixture containing 15 mM K(+) (optimum condition). However, cycleanine increased the K(0.5) value for K(+) and reduced the K(i) values for Na(+) and ATP, in K(+)-dependent p-nitrophenyl phosphatase. Cycleanine might interact with the enzyme in Na.E(1)-P form and prevents the reaction step from Na.E(1)-P to E(2)-P.


Different methods for anatomical targeting.
Several procedures are used in the different neurosurgical centers in order to perform stereotactic surgery for movement disorders. At the moment no procedure can really be considered superior to the other. We contribute with our experience of targeting method. Ten patients were selected, in accordance to the guidelines for the treatment of Parkinson disease, and operated by several methods including pallidotomy, bilateral insertion of chronic deep brain electrodes within the internal pallidum and in the subthalamic nucleus (18 procedures). in each patient an MR scan was performed the day before surgery. Scans were performed axially parallel to the intercommissural line. The operating day a contrast CT scan was performed under stereotactic conditions. after digitalization of the MRI images, it was possible to visualize the surgical target and to relate it to parenchimal and vascular anatomic structures readable at the CT examination. The CT scan obtained was confronted with the MR previously performed, the geometrical relation between the different parenchimal and vascular structures and the selected targets were obtained. Stereotactic coordinates were obtained on the CT examination. It was possible to calculate the position of the subthalamic nucleus and of the internal pallidum on the CT scan, not only relating to the intercommissural line, but considering also the neurovascular structures displayed both on the MRI and the CT scans. The technique that our group presents consist in an integration between information derived from the CT and the MR techniques, so that we can benefit from the advantages of both methods and overcome the disadvantages.


[Matrix metalloproteinases and their tissue inhibitors in basal cell and metatypical cancer of the skin].
10 cases of ulcerative-nodular basal cell carcinoma and 10 cases of metatypical carcinoma of the skin were studied immunohistochemically for immunoexpression of matrix metalloproteinases (MMP-1, MMP-9) and their endogenic tissue inhibitors (TIMP-1, TIMP-2) in combination with PCNA, p53 tumor complexes. Some differences are found in these types of tumors.


Carbon tetrachloride-induced cell death in perfused livers from phenobarbital-pretreated rats under hypoxic conditions and various ionic milieu. Further evidence for calcium-dependent irreversible changes.
The role of Ca2+ in the initiation of carbon tetrachloride (CCl4) hepatotoxicity was studied using perfused livers isolated from phenobarbital-pretreated rats in a single-pass system. Krebs-Henseleit bicarbonate buffer containing 1.3 mM CaCl2 (KHB) was the regular ionic milieu. In the liver perfused with fructose-supplemented regular KHB equilibrated with 95% N2-5% CO2, infusion of 0.5 mM CCl4 caused an early uptake of Ca2+ coupled with K+ leakage and Na+ uptake within the infusion time of 30 min, which was followed by a marked lactic dehydrogenase (LDH) leakage into the effluent perfusate and further Ca2+ uptake by the liver. With Ca(2+)-free medium, the prenecrotic K+ leakage and the successive LDH leakage were suppressed markedly. However, a perfusate exchange from regular to Ca(2+)-free KHB at the end of the prenecrotic stage did not protect against the LDH leakage, and the perfusate exchange conversely did not produce LDH leakage. Perfusion of the liver with high K+(Cl-) medium under 20% O2 markedly suppressed CCl4-induced LDH leakage even in the presence of Ca2+, whereas once CCl4 had acted under regular KHB perfusion, changing the medium to high K+ did not further prevent the LDH leakage. High K(+)-lactobionic acid medium containing Ca2+ and supplemented with fructose also suppressed LDH leakage under 95% N2 without the accompanying prenecrotic Ca2+ uptake. However, a change of the medium after CCl4 infusion to regular KHB containing Ca2+ caused LDH leakage and K+ leakage, with Ca2+ uptake. The prevention of LDH leakage in a different ionic milieu may not be due to suppression of CCl4 bioactivation, since the liver cytochrome P450 content decreased to a similar extent. These findings suggest that entry of extracellular Ca2+ into hepatocytes coupled with K+ leakage and Na+ entry is a prerequisite for CCl4-induced hepatocyte death and that association of Ca2+ with a CCl4-derived radical-mediated process may be necessary for early and irreversible plasma membrane damage.


Ultrasound-mediated gene transfection: problems to be solved and future possibilities.
Together, the human genome project and advances in molecular biology have led to identification of many genes, some useful in the field of medicine. Gene therapy has opened a potentially new therapeutic avenue for managing an array of complicated diseases. One of the more critical areas of gene therapy is the design of an appropriate, accurate, and effective gene transfer system that can be safely applied in vivo. Because no known system meets all the requirements for clinical use, a better, more versatile method of gene transfer is desired. Ultrasound-mediated transfection (USMT) could serve as a potential site-specific gene transfer modality. Although no actual mechanism has yet been thoroughly described, we focus on the principles of USMT, discuss the use of microbubbles as a gene-transfer mechanism, and summarize preliminary in vivo experiments using microbubbles as vectors. Although the published data suggest the promise of this method, extensive improvement in USMT remains essential. Reassuringly, recent success in USMT research has positioned ultrasound as a highly safe modality for gene transfer.


Child and case influences on recidivism in a statewide dissemination of Multisystemic Therapy for juvenile offenders.
Multisystemic Therapy (MST) is an evidence-based treatment for high-risk youth and their families shown to reduce subsequent delinquent activity. This study investigated (1) re-arrest rates of a statewide MST dissemination; and (2) the relation of child, family, and case characteristics to re-arrest rates following receipt of MST. Analyses examined outcomes for 633 youth following referral to MST. Separate models examined predictors of general re-arrest of any type and of more serious misdemeanor or felony arrests. Sixty-five percent of youth experienced a new arrest of any type within 12-months of MST initiation; fewer (53%) experienced a misdemeanor or felony charge in that timeframe. Recipients who were younger, had an externalizing behavior disorder, and had a greater number and severity of pre-MST charges were more likely to recidivate. Findings highlight potential child and case factors that may account for variability in treatment effects when MST is implemented broadly within a system.


Development of a fluorine-18 radiolabelled fluorescent chalcone: evaluated for detecting glycogen.
Glycogen is a multibranched polysaccharide of glucose produced by cells to store energy and plays a key role in cancer. A previously reported fluorescent probe (CDg4) was shown to selectively bind glycogen in mouse embryonic stem cells, however the molecule was not evaluated in cancer cells. We report the synthesis and biological evaluation of a dual-modality imaging probe based on CDg4, for positron emission tomography (PET) and fluorescence microscopy. A fluorine-18 radiolabelled derivative of CDg4, ([18F]5) for in vivo quantification of total glycogen levels in cancer cells was developed and synthesised in 170 min with a non-decay corrected radiochemical yield (RCY n.d.c) of 5.1 ± 0.9% (n = 4) in > 98% radiochemical purity. Compound 5 and [18F]5 were evaluated in vitro for their potential to bind glycogen, but only 5 showed accumulation by fluorescence microscopy. The accumulation of 5 was determined to be specific as fluorescent signal diminished upon the digestion of carbohydrate polymers with α-amylase. PET imaging in non-tumour bearing mice highlighted rapid hepato-biliary-intestinal elimination of [18F]5 and almost complete metabolic degradation after 60 min in the liver, plasma and urine, confirmed by radioactive metabolite analysis. Fluorescent compound 5 selectively accumulated in glycogen containing cancer cells, identified by fluorescence microscopy; however, rapid in vivo metabolic degradation precludes further investigation of [18F]5 as a PET radiopharmaceutical.


Dipyridamole, cerebrovascular disease, and the vasculature.
Stroke is a leading cause of morbidity and mortality and the most common cause of neurological disability in older individuals. Prevention of recurrent stroke includes risk factor modification as well as the use of therapies that inhibit platelet activation. One such recommended therapy, dipyridamole, is given in combination with aspirin. Dipyridamole's inhibitory effect is thought to be due to inhibition of the adenosine transporter leading to an increase in cAMP, an inhibitor of platelet aggregation. However, recent studies suggest that dipyridamole possesses beneficial properties in vasculature in addition to anti-platelet effects. This includes direct and indirect effects on the endothelium such as inhibition of proliferation, antioxidant, and anti-inflammatory properties as well as their subsequent effect on cell signaling. The purpose of this review is to examine whether the recently identified beneficial antioxidant and anti-inflammatory properties of aspirin/extended-release dipyridamole may partially underlie the clinical benefits observed in the secondary prevention of stroke.


The clinical utility of rapid exome sequencing in a consanguineous population.
The clinical utility of exome sequencing is now well documented. Rapid exome sequencing (RES) is more resource-intensive than regular exome sequencing and is typically employed in specialized clinical settings wherein urgent molecular diagnosis is thought to influence acute management. Studies on the clinical utility of RES have been largely limited to outbred populations. Here, we describe our experience with rapid exome sequencing (RES) in a highly consanguineous population. Clinical settings included intensive care units, prenatal cases approaching the legal cutoff for termination, and urgent transplant decisions. A positive molecular finding (a pathogenic or likely pathogenic variant that explains the phenotype) was observed in 80 of 189 cases (42%), while 15 (8%) and 94 (50%) received ambiguous (variant of uncertain significance (VUS)) and negative results, respectively. The consanguineous nature of the study population gave us an opportunity to observe highly unusual and severe phenotypic expressions of previously reported genes. Clinical utility was observed in nearly all (79/80) cases with positive molecular findings and included management decisions, prognostication, and reproductive counseling. Reproductive counseling is a particularly important utility in this population where the overwhelming majority (86%) of identified variants are autosomal recessive, which are more actionable in this regard than the de novo variants typically reported by RES elsewhere. Indeed, our cost-effectiveness analysis shows compelling cost savings in the study population. This work expands the diversity of environments in which RES has a demonstrable clinical utility.


Stimulation of a ouabain-sensitive Rb+ uptake in human erthrocytes with an external electric field.
(Na, K)ATPase of the red blood cell (RBC) is known to be electrogenic. Activation of this pump hyperpolarizes the RBC membrane by several millivolts. By exposing erythrocytes in an isotonic suspension to an alternating electric field it is possible to modulate transmembrane potential (delta psi) of the RBC. We have found that this modulation stimulates uptake of Rb+, against a chemical concentration gradient, when the applied AC field exceeds 10 V/cm (or an induced delta psi of 6 mV). The voltage-stimulated Rb+ uptake is completely inhibited by ouabain. Thus, (Na, K)ATPase may be involved. The stimulated Rb+ uptake is unrelated to the thermal effect by several lines of evidence. First, this uptake is above levels in controlled samples maintained at an identical temperature. Second, this uptake shows an optimum voltage. The maximum stimulation obtained in our experiment (26 amol/RBC X hr) occurs at 20 V/cm, i.e., a delta psi of 12 mV. Above or below this field strength the uptake is reduced. Third, this uptake is AC frequency dependent. It peaks around 1 kHz and diminishes at 1 MHz. The effective range is between 0.1 kHz to 0.1 MHz. A thermal effect would not be frequency dependent. In contrast to the ATP-dependent pumping activity of the (Na, K)ATPase, no stimulated Na+ efflux is detectable with the AC field. Neither Rb+ efflux, nor Na+ influx is stimulated by the AC field. Rb+ uptake is also stimulated by the AC field in a RBC sample treated with vanadate. The meaning of these observations is discussed.


A test of the karyotypic fissioning theory of primate evolution.
Karyotypic fissioning theory has been put forward by a number of researchers as a possible driving force of mammalian evolution. Most recently, Giusto and Margulis (BioSystems, 13 (1981) 267-302) hypothesized that karyotypic fissioning best explains the evolution of Old World monkeys, apes, and humans. According to their hypothesis, hominoid karyotypes were derived from the monkey chromosome complement by just such a fissioning event. That hypothesis is tested here by comparing the G-banded chromosomes of humans and great apes with eight species of Old World monkeys. Five submetacentric chromosomes between apes and monkeys have identical banding patterns and nine chromosomes share the same pericentric inversion. Such extensive karyological similarities are not in accordance with, or predicted by karyotypic fissioning. Apparently, karyotypic fissioning is an extremely uneconomical model of chromosomal evolution. The strong conservation of banding patterns sometimes involving the retention of identical chromosomes indicates that ancient linkages of genes have probably been maintained through many speciation events.


Environmental, ecological and methodological factors of Tonic Immobility (TI) modulation.
Modulation of Tonic Immobility (TI) concerns environmental and individual factors. TI is modulated by processes of habituation and sensitization. In poikilotherm frog and lizard, TI duration is much shorter at usual environmental temperatures and is potentiated at higher or lower temperatures, as the last resource for survival. During ontogeny, age may differentially affect TI susceptibility to the induction procedures, as in the case of newborn ectothermic and older endothermic rabbits. TI duration displays a daily rhythm, with longer TI in the night. Its resistance to habituation indicates that in the dark TI is the most prominent defense against nocturnal predators. In all studied species, there is synchronization of the prey's defensive responses with the feeding activity of predators. Ecological factors and exposure to different anthropogenic environmental pressures may alter morphology, behavior and TI in wild populations. TI duration has been associated with a genomic region comprising the dystrophin gene on quail chromosome 1.


Depression care among adults with co-occurring major depressive episodes and substance use disorders in the United States.
We examined 12-month prevalence and correlates of receiving depression care and perceiving helpfulness of depression care among U.S. adults with major depressive episodes (MDE) and substance use disorders (SUD). Data were from 325,800 adults who participated in the 2008-2014 National Surveys on Drug Use and Health (NSDUH). Descriptive analyses and bivariable and multivariable logistic regression models were applied. In the U.S., 3.3 million adults (1.4% of the adult population) had co-occurring MDE and SUD in the past year. Among adults with both disorders, 55.4% reported receiving past-year depression care. Among those with past-year depression care, 36.1% perceived it as helpful. Compared with adults who did not receive substance use treatment in the past year, those who received substance use treatment were significantly more likely to receive depression care, and those who received treatment of both disorders were more likely to perceive their depression care as helpful (adjusted risk ratios (ARRs) = 1.5-1.6). Compared with adults who received depression care only from general medical providers, those who received depression care from specialty mental health providers were more likely to report that their care was helpful (ARRs = 1.4-1.6). Receipt of prescription medication for MDE was associated with perceived helpfulness of depression care (ARR = 1.3, 95% CI = 1.05-1.73). Almost half of adults with co-occurring MDE and SUD did not receive past-year depression care. Among those who received depression care, most did not perceive it as helpful. Substance use treatment, specialty mental health treatment, and antidepressant medications were perceived as helpful aspects of depression care.


Simultaneous in vivo comparison of bone substitutes in a guided bone regeneration model.
A direct, simultaneous comparison of bone substitutes is hampered by the limited number of samples that can be tested simultaneously. The goal of this study was to establish a preclinical model for guided bone regeneration that offers testing of different bone substitutes in a one-wall defect situation. We show here that up to eight titanium hemispheres can be placed on the calvaria of minipigs. To establish our model, titanium hemispheres were filled with and without Bio-Oss, a deproteinized bovine bone mineral, Ostim, an aqueous paste of synthetic nanoparticular hydroxyapatite, and Osteoinductal, an oily calcium hydroxide suspension, before being positioned on the calvaria. After 6 and 12 weeks, titanium hemispheres were subjected to histological and histomorphometric analysis. We show here that bone filled approximately one-tenth of the area below the hemispheres which were left empty, indicating a critical size model for guided bone regeneration. In accordance with the documented osteoconductive properties of Bio-Oss and Ostim, titanium hemispheres were almost completely filled with bone. Moreover, the expected degradation profile of Bio-Oss and Ostim could be confirmed by histologic and histomorphometric analysis. Under the same conditions, Osteoinductal failed to exert osteoconductive properties, rather a progressive resorption of the host bone was observed. These results demonstrate that the preclinical model presented here is suitable to simultaneously compare bone substitutes with different material properties. Our model based on the titanium hemispheres allows evaluation of graft consolidation under standardized conditions thereby avoiding intra-individual variations.


Thalamo-cortical interactions modeled by weakly connected oscillators: could the brain use FM radio principles?
We consider all models of the thalamo-cortical system that satisfy the following two assumptions: (1) each cortical column is an autonomous oscillator; (2) connections between cortical columns and the thalamus are weak. Our goal is to deduce from these assumptions general principles of thalamo-cortical interactions that are independent of the equations describing the system. We find that the existence of synaptic connections between any two cortical columns does not guarantee that the columns interact: They interact only when there is a certain nearly resonant relation between their frequencies, which implies that the interactions are frequency modulated (FM). When the resonance relation holds, the cortical columns interact through phase modulations. Thus, communications between weakly connected cortical oscillators employ a principle similar to that in FM radio: The frequency of oscillation encodes the channel of communication, while the information is transmitted via phase modulations. If the thalamic input has an appropriate frequency, then it can dynamically link any two cortical columns, even those that have non-resonant frequencies and would otherwise be unlinked. Thus, by adjusting its temporal activity, the thalamus has control over information processing taking place in the cortex. Our results suggest that the mean firing rate (frequency) of periodically spiking neuron does not carry any information other than identifying a channel of communication. Information (i.e. neural code) is carried through modulations of interspike intervals.


American childhood football as a possible risk factor for cerebral infarction.
Three adolescent football players who had ischemic stroke associated with football practice and play are described. The literature on stroke associated with childhood sports and football in particular is reviewed, and the multiple mechanisms by which football can contribute to ischemic stroke are discussed.


Immunoelectron microscopy of amylase in the human parotid gland. Ultrastructural localization by use of both the protein A-gold and the biotin-avidin-gold technique.
Specimens of the human parotid gland were studied by immuno-electron microscopy for the presence of amylase. Both the protein A-gold technique and the biotin-avidin-gold technique were used on the same specimens. Different fixations were tried. Amylase was detected in the zymogen granules in high amounts. This enzyme could even be seen in glutaraldehyde fixed and routinely embedded material. The subcellular localization of this enzyme opens a new field of functional morphological studies and studies in special tumours including acinic cell carcinomas.


Interactions between Ca(2+)-mobilizing receptors and their G proteins in hepatocytes.
In hepatocytes, different receptors that share an ability to stimulate inositol 1,4,5-trisphosphate formation by activating guanine nucleotide-binding proteins (G proteins) evoke Ca2+ signals that are characteristic of the receptor that evoked them. High affinity, guanine nucleotide-sensitive binding of agonists to their receptors provides a convenient means of assessing receptor-G protein interactions. We used these methods to examine the extent to which different Ca(2+)-mobilizing receptors share G protein pools. Although our earlier results (Dasso, L. L. T., and Taylor, C.W. (1992) Mol. Pharmacol. 42, 453-457) showed that activated V1-vasopressin receptors prevented alpha 1-adrenoreceptors from associating with G proteins, our present results show that neither alpha 1-adrenergic agonists nor angiotensin II influences the interaction between V1 receptors and their G proteins. This asymmetric scavenging of G proteins by alpha 1-adrenoreceptors and V1 receptors is not a consequence of there being more of the latter and may result either from V1 receptors binding more tightly to G proteins or from their ability to interact with a second G protein pool. We speculate that the different interactions among V1 receptors, alpha 1-adrenoreceptors, and their G proteins contribute to the differently shaped Ca2+ spikes evoked by these receptors.