MRI of cervical spine with flexion and extension used in patients with rheumatoid arthritis.
Patients with rheumatoid arthritis (RA) often have involvement of the cervical spine. The most common abnormality is atlanto-axial subluxation (AAS). The more serious vertical subluxation (VS) is thought to develop at a later stage. Direct cord compression may occur, but the symptoms may be vague and difficult to interpret. In addition to clinical follow up, RA patients undergo several conventional radiographs of the cervical spine, with addition of flexion and extension images. This, in spite of the fact that the cervical cord and soft tissue do not show. Magnetic resonance imaging (MRI), is the modality of choice to visualize soft tissue and the cervical medulla, but is rarely performed in the follow up of RA patients. Five patients with long-standing RA, episodes of neck pain, and known AAS were asked to volunteer for a MRI study of the cervical spine, consisting of sagittal T2 weighted images of the cervical spine during flexion and extension of the neck. Compared to clinical examinations and cervical radiographs, MRI gave valuable information not otherwise obtained. The importance of MRI with the neck in a flexed and extended position is stressed. This is possible to obtain within a conventional quadrature neck coil in many RA patients.


Brown Seaweed Consumption as a Promising Strategy for Blood Glucose Management: A Comprehensive Meta-Analysis.
Diabetes is a chronic condition that can lead to various complications; therefore, there is a need to emphasize prevention and management. Dietary interventions, such as the Mediterranean diet or calorie-restricted regimens, coupled with exercise-induced weight reduction, have been recommended for enhancing diabetes management. Seaweeds contain various functional components, such as polyphenols and fucoidan, which have been reported to exert multiple benefits, including blood glucose regulation, improved intestinal health, and enhanced of lipid profiles. The association between blood glucose and seaweed consumption has been established in previous research. We searched the PubMed, RISS, Google Scholar, ScienceDirect, and Cochrane Library databases to identify relevant studies after applying the selection/exclusion criteria, and 23 studies were ultimately included in this analysis. Comprehensive Meta-Analysis (CMA) software version 4.0 was used to assess statistical significance and heterogeneity. In this meta-analysis, postprandial blood glucose, glycated hemoglobin (HbA1c), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels demonstrated significant improvements in the seaweed group compared to the control group. Conversely, fasting blood glucose and insulin levels did not show significant associations with seaweed consumption. Subgroup analysis revealed that a high dose (1000 mg or more) was more beneficial than a low dose, and seaweeds such as Laminaria digitata, Undaria pinnatifida, Acophyllum nodosum, and Fucus vesiculosus were found to be more effective at improving blood glucose levels than control treatments. Therefore, based on our research, seaweed supplementation appears to be a promising strategy for reducing postprandial blood glucose, HbA1c, and HOMA-IR levels, thereby enabling better blood glucose management and leading to a decreased risk of type 2 diabetes.


A Rare Case of Solitary Kidney Metastasis Following Primary Laryngeal Squamous Cell Carcinoma.
Laryngeal cancer is the 14th most common malignancy worldwide, and its common subtype squamous cell carcinoma (SCC) is highly associated with tobacco use and long-term alcohol consumption. The incidence of distant metastasis from a primary laryngeal cancer has been reported to be very low, between 6.5% and 8.5%, according to published tumour registry data. Distant metastases of laryngeal SCC most commonly involve the lung, liver, bone and mediastinum, seldom involving the kidney. Renal metastasis has been well established in many other cancers such as lymphoma, lung, breast and gastric carcinoma. This report discusses the rare case of a solitary renal metastasis following a primary laryngeal SCC.


Predictive ability of genome-assisted statistical models under various forms of gene action.
Recent work has suggested that the performance of prediction models for complex traits may depend on the architecture of the target traits. Here we compared several prediction models with respect to their ability of predicting phenotypes under various statistical architectures of gene action: (1) purely additive, (2) additive and dominance, (3) additive, dominance, and two-locus epistasis, and (4) purely epistatic settings. Simulation and a real chicken dataset were used. Fourteen prediction models were compared: BayesA, BayesB, BayesC, Bayesian LASSO, Bayesian ridge regression, elastic net, genomic best linear unbiased prediction, a Gaussian process, LASSO, random forests, reproducing kernel Hilbert spaces regression, ridge regression (best linear unbiased prediction), relevance vector machines, and support vector machines. When the trait was under additive gene action, the parametric prediction models outperformed non-parametric ones. Conversely, when the trait was under epistatic gene action, the non-parametric prediction models provided more accurate predictions. Thus, prediction models must be selected according to the most probably underlying architecture of traits. In the chicken dataset examined, most models had similar prediction performance. Our results corroborate the view that there is no universally best prediction models, and that the development of robust prediction models is an important research objective.


Association of anthropometric measures with fat and fat-free mass in the elderly: The Rotterdam study.
The decrease in fat-free mass (FFM) seen in many elderly people is usually associated with an increase in fat mass (FM), a state referred to as sarcopenic obesity. It is not clear which anthropometric measures are best used to identify sarcopenic obesity. We therefore evaluated which anthropometric measures are differentially associated with FM and FFM. The anthropometric measures tested were body mass index (BMI), waist circumference (WC), and a body shape index (ABSI = WC/(BMI(2/3)*Height(1/2))). FM and FFM were estimated by dual-energy X-ray absorptiometry. An index-score was calculated for both FM (FMI) and FFM (FFMI) by dividing FM and FFM by height. Multivariable linear regression models were used to assess the associations of BMI, WC and ABSI with FMI and FFMI among 3612 participants (2092 women) from the prospective population-based Rotterdam Study. In multivariate models adjusted for confounders, BMI and WC were positively associated with both FMI and FFMI in men and women. ABSI was positively associated with FMI (β 1.01, 95% confidence interval (95%CI) 0.85, 1.17) and negatively associated with FFMI (β -0.28, 95%CI -0.38, -0.17) in men. In women, ABSI was not associated with FMI and was positively associated with FFMI (β 0.18, 95%CI 0.10, 0.26). While BMI and WC were both positively associated with FM and FFM, ABSI showed a differential association with FM and FFM in men, but not in women. Since sarcopenic obesity is associated with decreased FFM and increased FM, ABSI could be a useful tool for identifying men at higher risk of sarcopenic obesity.


Elderly suicide in Singapore.
The suicide rate in Singapore has remained at 9-11 per 100,000 over the past decade. Comparing the age specific suicide rate, elderly people (60 years and above) have a much higher rate (21.3 per 1000,000) than the young (5 per 100,000). The data also indicate that elderly men are more prone to kill themselves than elderly women. Risk factors in elderly suicide and preventive measures are discussed.


Primary role of sarcoplasmic reticulum in phasic contractile activation of cardiac myocytes with shunted myolemma.
Homogeneous populations of single myocytes showing good preservation of ultrastructure were obtained by enzymatic digestion of rabbit and rat hearts, and maintained in a relaxed state in the presence of free Ca2+ concentrations less than 10(-7) M. Ultrastructural details such as a cytoskeleton of 100-A filaments connected to the sarcolemma at the Z lines were demonstrated especially well in these preparations. In spite of seemingly normal structure, electron probe analysis of cryosections reveals similar concentrations of electrolytes in the medium and in the cytoplasm, indicating the presence of electrochemical shunting across the external membrane. The dissociated myocytes display Ca uptake and phasic contractions that are apparently dependent on mitochondrial respiration, but are not affected by mitochondrial uncouplers when ATP and phosphocreatine are added. The uptake is augmented by oxalate and, based on identification of calcium oxalate crystals by electron microscopy and electron probe analysis, is localized to the sarcoplasmic reticulum (SR). An advantageous feature of the dissociated myocytes is that they are suitable for experiments using large numbers of cells in suspension. Thereby, velocities of calcium transport were measured directly by isotopic tracer and filtration methods. It was then found that the lowest CA2+ concentrations (5 x 10(-7) M for the rabbit and 1 x 10(-7) M for the rat) sustaining Ca transport also induce phasic contractile activity in all myocytes, even though the external membrane is electrochemically shunted. A stepwise rise in the Ca2+ concentration of up to one order of magnitude, increases transport velocities in parallel with the rates of phasic contractions. Both these parameters are affected by Mg2+, temperature, cyclic-AMP, and methylxanthines, even though the Ca2+ concentration is maintained constant in the medium. Therefore, Ca transport by SR is a requirement and a rate limiting factor for the occurrence of phasic contractile activation in dissociated cardiac cells retaining an electrochemically shunted external membrane. It is suggested that transient Ca release required for phasic contractile activation is due to equilibrium oscillations across the SR membrane. The sequential pattern of sarcomere activation is consistent with a self propagating mechanism of calcium release. SR in dissociated skeletal muscle cells sustains a greater Ca transport activity than in dissociated heart cells. However, the heart cells display a much higher phasic contractile activity, indicating that cardiac SR has a greater tendency to release accumulated calcium. If free Ca2+ in the medium is raised above 10(-6) M, both cardiac and skeletal myocytes undergo contractures and degenerative phenomena, accompanied by Ca, Mg, and phosphate accumulation in cardiac mitochondria.


Microplastics and Nanoplastics Impair the Biophysical Function of Pulmonary Surfactant by Forming Heteroaggregates at the Alveolar-Capillary Interface.
Microplastics (MPs) are ubiquitous environmental pollutants produced through the degradation of plastic products. Nanoplastics (NPs), commonly coexisting with MPs in the environment, are submicrometer debris incidentally produced from fragmentation of MPs. We studied the biophysical impacts of MPs/NPs derived from commonly used commercial plastic products on a natural pulmonary surfactant extracted from calf lung lavage. It was found that in comparison to MPs/NPs derived from lunch boxes made of polypropylene or from drinking water bottles made of poly(ethylene terephthalate), the MP/NP derived from foam packaging boxes made of polystyrene showed the highest adverse impact on the biophysical function of the pulmonary surfactant. Accordingly, intranasal exposure of MP/NP derived from the foam boxes also induced the most serious proinflammatory responses and lung injury in mice. Atomic force microscopy revealed that NP particles were adsorbed on the air-water surface and heteroaggregated with the pulmonary surfactant film. These results indicate that although the incidentally formed NPs only make up a small mass fraction, they likely play a predominant role in determining the nano-bio interactions and the lung toxicity of MPs/NPs by forming heteroaggregates at the alveolar-capillary interface. These findings may provide novel insights into understanding the health impact of MPs and NPs on the respiratory system.


One-Step Hydrothermal Synthesis of Cu2ZnSnS4 Nanoparticles as an Efficient Visible Light Photocatalyst for the Degradation of Congo Red Azo Dye.
A hydrothermal method was successfully employed to synthesize kesterite Cu2ZnSnS4 (CZTS) nanoparticles. X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), and optical ultraviolet-visible (UV-vis) spectroscopy were used for characterization of structural, chemical, morphological, and optical properties. XRD results confirmed that a nanocrystalline CZTS phase corresponding to the kesterite structure was formed. Raman analysis confirmed the existence of single pure phase CZTS. XPS results revealed the oxidation states as Cu+, Zn2+, Sn4+, and S2-. FESEM and TEM micrograph images revealed the presence of nanoparticles with average sizes between 7 nm to 60 nm. The synthesized CZTS nanoparticles bandgap was found to be 1.5 eV which is optimal for solar photocatalytic degradation applications. The properties as a semiconductor material were evaluated through the Mott-Schottky analysis. The photocatalytic activity of CZTS has been investigated through photodegradation of Congo red azo dye solution under solar simulation light irradiation, proving to be an excellent photo-catalyst for CR where 90.2% degradation could be achieved in just 60 min. Furthermore, the prepared CZTS was reusable and can be repeatedly used to remove Congo red dye from aqueous solutions.


Contractile responses to histamine of isolated pulmonary artery strips from healthy and heartworm-infected dogs.
Pulmonary artery strips from control and Dirofilaria immitis-infected dogs were tested for isometric contractile response to histamine, carbamylcholine, and norepinephrine. The strips from D immitis-positive dogs showed diminished response to histamine; a smaller percentage of the strips contracted, and the magnitude of the contraction was less than the response of the control strips to the highest concentration used. Carbamylcholine caused virtually no contractile effect in either group. Norepinephrine contracted all strips, even those not responding to histamine. A role for histamine in the pathogenesis of the pulmonary arterial lesions associated with dirofilariasis is presented.


Proteomic Analysis of Fractionated Eimeria tenella Sporulated Oocysts Reveals Involvement in Oocyst Wall Formation.
Eimeria tenella is the most pathogenic intracellular protozoan parasite of the Eimeria species. Eimeria oocyst wall biogenesis appears to play a central role in oocyst transmission. Proteome profiling offers insights into the mechanisms governing the molecular basis of oocyst wall formation and identifies targets for blocking parasite transmission. Tandem mass tags (TMT)-labeled quantitative proteomics was used to analyze the oocyst wall and sporocysts of E. tenella. A combined total of 2865 E. tenella proteins were identified in the oocyst wall and sporocyst fractions; among these, 401 DEPs were identified, of which 211 were upregulated and 190 were downregulated. The 211 up-regulated DEPs were involved in various biological processes, including DNA replication, fatty acid metabolism and biosynthesis, glutathione metabolism, and propanoate metabolism. Among these proteins, several are of interest for their likely role in oocyst wall formation, including two tyrosine-rich gametocyte proteins (EtGAM56, EtSWP1) and two cysteine-rich proteins (EtOWP2, EtOWP6). Concurrently, 96 uncharacterized proteins may also participate in oocyst wall formation. The present study significantly expands our knowledge of the proteome of the oocyst wall of E. tenella, thereby providing a theoretical basis for further understanding of the biosynthesis and resilience of the E. tenella oocyst wall.


Evaluations of combined zebrafish (Danio rerio) embryo and marine phytoplankton (Diacronema lutheri) toxicity of dissolved organic contaminants in the Ythan catchment, Scotland, UK.
A wide variety of organic contaminants including pesticides, polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) have previously been detected in surface waters in the river Ythan catchment, North East Scotland UK. While the concentrations detected were below Water Framework Directive Environmental Quality Standards (WFD-EQSs) environmental exposures to the diverse mixtures of contaminants, known and unknown, may pose chronic and/or sublethal effects to non target organisms. The present study assessed the embryo and algal toxicity potential of freely dissolved organic contaminants from the Ythan catchment using silicone rubber passive sampling devices (SR-PSDs) and miniaturised bioassay techniques. Zebrafish (Danio rerio) embryos and marine phytoplankton species (Diacronema lutheri) were exposed to extracts from SR-PSDs deployed at different locations along the river Ythan and an undeployed procedural blank. Statistically significant developmental and algal toxicities were measured in all tests of extracts from deployed samples compared with the procedural blanks. This indicates environmental exposure to, and the combined toxicity potential of, freely dissolved organic contaminants in the catchment. The present and previous studies in the Ythan catchment, coupling SR-PSDs and bioassay techniques, have both helped to understand the interactions and combined effects of dissolved organic contaminants in the catchment. They have further revealed the need for improvement in the techniques currently used to assess environmental impact.


Three-dimensional analysis of cylindrical microresonators based on the aperiodic Fourier modal method.
We develop a 3D vectorial description of microresonators of the microdisk and microring types based on the aperiodic Fourier modal method. Such a rigorous coupled-wave analysis allows us to evaluate accurately the resonant wavelengths, the quality factor, and the full profile of whispering-gallery modes. The results are compared with 2D (effective index) as well as 3D finite-difference time domain calculations.


In Silico Identification of Cholesterol Binding Motifs in the Chemokine Receptor CCR3.
CC motif chemokine receptor 3 (CCR3) is a Class A G protein-coupled receptor (GPCR) mainly responsible for the cellular trafficking of eosinophils. As such, it plays key roles in inflammatory conditions, such as asthma and arthritis, and the metastasis of many deadly forms of cancer. However, little is known about how CCR3 functionally interacts with its bilayer environment. Here, we investigate cholesterol binding sites in silico through Coarse-Grained Molecular Dynamics (MD) and Pylipid analysis using an extensively validated homology model based on the crystal structure of CCR5. These simulations identified several cholesterol binding sites containing Cholesterol Recognition/Interaction Amino Acid Consensus motif (CRAC) and its inversion CARC motifs in CCR3. One such site, a CARC site in TM1, in conjunction with aliphatic residues in TM7, emerged as a candidate for future investigation based on the cholesterol residency time within the binding pocket. This site forms the core of a cholesterol binding site previously observed in computational studies of CCR2 and CCR5. Most importantly, these cholesterol binding sites are conserved in other chemokine receptors and may provide clues to cholesterol regulation mechanisms in this subfamily of Class A GPCRs.


Reactive oxygen species formation and apoptosis in human peripheral blood mononuclear cell induced by 900 MHz mobile phone radiation.
We demonstrate that reactive oxygen species (ROS) plays an important role in the process of apoptosis in human peripheral blood mononuclear cell (PBMC) which is induced by the radiation of 900 MHz radiofrequency electromagnetic field (RFEMF) at a specific absorption rate (SAR) of ~0.4 W/kg when the exposure lasts longer than two hours. The apoptosis is induced through the mitochondrial pathway and mediated by activating ROS and caspase-3, and decreasing the mitochondrial potential. The activation of ROS is triggered by the conformation disturbance of lipids, protein, and DNA induced by the exposure of GSM RFEMF. Although human PBMC was found to have a self-protection mechanism of releasing carotenoid in response to oxidative stress to lessen the further increase of ROS, the imbalance between the antioxidant defenses and ROS formation still results in an increase of cell death with the exposure time and can cause about 37% human PBMC death in eight hours.


Pomegranate Juice Polyphenols Induce Macrophage Death via Apoptosis as Opposed to Necrosis Induced by Free Radical Generation: A Central Role for Oxidative Stress.
At high concentrations, polyphenols induce cell death, and the polyphenols-rich pomegranate juice (PJ), known for its antioxidative/antiatherogenic properties, can possibly affect cell death, including macrophage death involved in atherogenesis. In the present study, apoptotic/necrotic macrophage death was analyzed in J774A.1 macrophages and in peritoneal macrophages isolated from atherosclerotic apoE-/- mice treated with PJ. The effects of PJ were compared with those of the free radical generator 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH). Both PJ and AAPH significantly increased J774A.1 macrophage death; however, flow cytometric and microscopic analyses using annexin V/propidium iodide revealed that PJ increased the early apoptosis of the macrophage dose dependently (up to 2.5-fold, P < 0.01), whereas AAPH caused dose-dependent increases in late apoptosis/necrosis (up to 12-fold, P < 0.001). Unlike PJ, AAPH-induced macrophage death was associated with increased intracellular oxidative stress (up to 7-fold, P < 0.001) and with lipid stress demonstrated by triglyceride accumulation (up to 3-fold, P < 0.01) and greater chromatic vesicle response to culture medium (up to 5-fold, P < 0.001). Accordingly, recombinant paraoxonase 1, which hydrolyzes oxidized lipids, attenuated macrophage death induced by AAPH, but not by PJ. Similar apoptotic and oxidative effects were found in macrophages from apoE-/- mice treated with PJ or AAPH. As macrophage apoptotic/necrotic death has considerable impact on atherosclerosis progression, these findings may provide novel mechanisms for the antiatherogenicity of PJ.


Integrated Metabolomic and Transcriptomic Analysis Reveals the Flavonoid Regulatory Network by Eutrema EsMYB90.
Flavonoids are representative secondary metabolites with different metabolic functions in plants. Previous study found that ectopic expression of EsMYB90 from Eutremasalsugineum could strongly increase anthocyanin content in transgenic tobacco via regulating the expression of anthocyanin biosynthesis genes. In the present research, metabolome analysis showed that there existed 130 significantly differential metabolites, of which 23 metabolites enhanced more than 1000 times in EsMYB90 transgenic tobacco leaves relative to the control, and the top 10 of the increased metabolites included caffeic acid, cyanidin O-syringic acid, myricetin and naringin. A total of 50 markedly differential flavonoids including flavones (14), flavonols (13), flavone C-glycosides (9), flavanones (7), catechin derivatives (5), anthocyanins (1) and isoflavone (1) were identified, of which 46 metabolites were at a significantly enhanced level. Integrated analysis of metabolome and transcriptome revealed that ectopic expression of EsMYB90 in transgenic tobacco leaves is highly associated with the prominent up-regulation of 16 flavonoid metabolites and the corresponding 42 flavonoid biosynthesis structure genes in phenylpropanoid/flavonoid pathways. Dual luciferase assay documented that EsMYB90 strongly activated the transcription of NtANS and NtDFR genes via improving their promoter activity in transiently expressed tobacco leaves, suggesting that EsMYB90 functions as a key regulator on anthocyanin and flavonoid biosynthesis. Taken together, the crucial regulatory role of EsMYB90 on enhancing many flavonoid metabolite levels is clearly demonstrated via modulating flavonoid biosynthesis gene expression in the leaves of transgenic tobacco, which extends our understanding of the regulating mechanism of MYB transcription factor in the phenylpropanoid/flavonoid pathways and provides a new clue and tool for further investigation and genetic engineering of flavonoid metabolism in plants.


Back Pain in Adolescents: Characteristics, Quality of Life, and Drug Self-Management: A Cross-Sectional Study of 1301 Italian Students.
Back pain is one of the major problems for the public health system in the western world. The purposes of this study were to assess back pain in a large cohort of adolescents; to evaluate the prevalence, intensity, and features; and obtain information about drug management of this symptom. One thousand four hundred seventy-one healthy students aged 14 to 19 years were enrolled in the study. The subjects underwent a face-to-face interview using an ad hoc questionnaire, the Numeric Rating Scale, the Neuropathic Pain Symptom Inventory, and the Short-Form 36 questionnaire. Sixty-eight percent of adolescents reported moderate to severe pain, with a higher prevalence of moderate/severe pain in female. The intensity of pain was higher (P < 0.001) in females than in men. A correlation was found between pain and quality of life. Considering the adolescents with severe pain, 21.6% requested a doctor's opinion, and 18% used analgesics (63.2% of them without a doctor's prescription), with a frequency of about 2 times per month. We found that the prevalence of back pain in adolescents is very high, with the consequences on quality of life, and it becomes frequently a self-managed symptom. This should encourage research on the causes of pain in order to limit the risk factors underlying the pain development and obtain a good prevention strategy.


Preventing drowning through design--the contribution of human factors.
A number of routes can be followed towards the prevention of drowning, such as educating on water safety, installing barriers between non-intended users and water, mitigating the consequences of submersion incidents, and design. The human factor approach to safety is that design should always be the primary route. Human factors can be applied to the design of personal protective equipment such as buoyancy aids, barriers such as pool fencing, ancillary equipment such as swimming pool covers through to information and organisational factors such as safety signs and swimming campaigns. Design should consider all potential drowning scenarios and accommodate the characteristics of those at risk. A framework is presented with examples on how human factor principles can be applied to the design of potential drowning sites and products, with suggestions for methods and techniques that can be used in the key stages of predicting potential hazards and assessing risk.


Henry Ware Cattell and Walt Whitman's Brain.
Henry Ware Cattell was a prominent pathologist and medical editor in late 19th and early 20th century America. Strangely, his name is unknown to most medical historians but is more widely known by aficionados of Walt Whitman's poetry. In 1892, Cattell was involved in an incident that abruptly changed his life and decreased his commitment to pathology as a career. Cattell had been serving as the pathologist/prosector for the American Anthropometric Society at the time the poet Walt Whitman died. Cattell, the pathologist for the University of Pennsylvania's Wistar Institute, performed Whitman's autopsy on March 27, 1892; Whitman's brain was removed and was to join those of other prominent American intellectuals who had donated their brains to the Society's "Brain Club," but something went horribly wrong (allegedly, an assistant had dropped the brain and destroyed it) and Cattell kept this a secret. Full of self-doubt, Cattell was anguished about his inadequacies as a pathologist and was extremely worried about how all of this would affect his career when discovered. While still continuing to practice hospital-based pathology, he began to transition into an author and editor. This essay will provide a detailed biographical sketch of Henry Ware Cattell, address his sibling rivalry with his more famous brother James McKeen Cattell, briefly discuss the fad of 19th century intellectuals embracing the pseudo-science of phrenology and their participation in anatomical "brain clubs," and, finally, address the mystery of what happened to Walt Whitman's brain. Clin. Anat. 31:988-996, 2018. © 2018 Wiley Periodicals, Inc.


Analysis of risk factors for colonic diverticular bleeding and recurrence.
The increase in incidence of colonic diverticular bleeding is relative to an age-related rise in the incidence of colonic diverticulosis and use of antithrombotic medication. However, risk factors related to the onset, recurrence, and prophylaxis have not been established. Therefore, we aimed to determine risk factors for the onset and recurrence of colonic diverticular bleeding.An age- and sex-matched case-control study was performed to assess the risk factors for the onset of colonic diverticular bleeding. The distribution of diverticulosis, comorbidity, and medication were evaluated from medical records. We also assigned patients with a first-time bleeding into groups with and without rebleeding during follow-up to determine risk factors for recurrence.Bilateral colonic diverticulosis, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin (LDA), and anticoagulants were significant risk factors for the onset of colonic diverticular bleeding on multivariate analysis. In contrast, the use of selective cyclooxygenase-2 (COX-2) inhibitor was not a risk factor for the onset. The incidence of bleeding in direct oral anticoagulant and warfarin users was not different between the 2 groups. The cumulative recurrence rate at 1 year was 15%. Recurrence rate was significantly higher in patients with a prior history of colonic diverticular bleeding than those without. Steroid use was associated with recurrence.Extensive distribution of diverticulosis and use of nonselective NSAIDs, LDA, and anticoagulants are regarded as risk factors for the onset of colonic diverticular bleeding. In addition, a prior history of colonic diverticular bleeding is related to the recurrence.


The status of home care training for physician assistants.
Homebound individuals represent a medically underserved and rapidly growing population. Nonphysician practitioners--physician assistants and nurse practitioners--in the home care setting afford increased availability of and access to medical services by homebound patients.


Current Perspective on the Use of Opioids in Perioperative Medicine: An Evidence-Based Literature Review, National Survey of 70,000 Physicians, and Multidisciplinary Clinical Appraisal.
Opioids represent an important analgesic option for physicians managing acute pain in surgical patients. Opioid management is not without its drawbacks, however, and current trends suggest that opioids might be overused in the United States. An expert panel was convened to conduct a clinical appraisal regarding the use of opioids in the perioperative setting. The clinical appraisal consisted of the review, presentation, and assessment of current published evidence as it relates to the statement "Opioids are not overused in the United States, even though opioid adjunct therapy achieves greater pain control with less risk." The authors' evaluation of this statement was also compared with the results of a national survey of surgeons and anesthesiologists in the United States. We report the presented literature and proceedings of the panel discussion. The national survey revealed a wide range of opinions regarding opioid overuse in the United States. Current published evidence provides support for the efficacy of opioid therapy in surgical patients; however, it is not sufficient to conclude unequivocally that opioids are-or are not-overused in the management of acute surgical pain in the United States. Opioids remain a key component of multimodal perioperative analgesia, and strategic opioid use based on clinical considerations and patient-specific needs represents an opportunity to support improved postoperative outcomes and satisfaction. Future studies should focus on identifying optimal procedure-specific and patient-centered approaches to multimodal perioperative analgesia.


Hurthle cell neoplasms of thyroid in south-western region of Saudi Arabia.
Thyroid Hurthle cell neoplasm (THCN) is relatively rare. To describe the presentation, diagnostic approach and management of THCN in our institution. This was a retrospective chart review of all thyroid Hurthle cell neoplasms diagnosed at Aseer Central Hospital (ACH), Saudi Arabia during the period from October 1998 to April 2007. Data including clinical, cytopathologic, radiologic, histopathologic and surgical treatment were extracted for analysis. Nine patients were diagnosed as THCN (eight females and one male). Their ages ranged from 24-49 years. Three cases were Hurthle cell carcinomas and six cases were Hurthle cell adenomas. Carcinomas presented as solitary nodules (two cases) and as multinodular goiter (one case). Adenomas presented as solitary nodules (two cases), as multinodular goiter (three cases) and as diffuse swelling (one case). Fine needle aspiration cytology (FNAC) was diagnostic for THCN in two cases of carcinoma that presented as solitary nodules and hence total thyroidectomy was performed. Total thyroidectomy was also done in one case of adenoma. Hemithyroidectomy was performed in two cases of adenoma in which FNAC showed benign lesion and in one case of carcinoma based on clinical and ultrasonographic impression of benign MNG in the involved lobe and inconclusive FNAC result. Subtotal thyroidectomy was performed in one case of adenoma. Preoperative diagnosis and management of THCN is still a dilemma. Neither clinical nor FNAC findings can exclude carcinoma. Therefore a combination of clinical, radiological, FNAC and histopathological results should be used for a more definitive subtyping and proper management.


Myeloperoxidase and free iron levels: potential biomarkers for early detection and prognosis of ovarian cancer.
The study sought to identify whether a relationship exists between serum myeloperoxidase (MPO) and free iron with stages of ovarian cancer. Serum and tissue samples were collected from women with stages I through IV ovarian cancer, benign gynecologic conditions, inflammation, and healthy controls. Myeloperoxidase ELISA and VITROS Fe Slide assays were used to measure serum and tissue MPO and free iron levels, respectively. Data were analyzed with a one-way ANOVA with post-hoc comparisons (p < 0.05 considered significant). There was a significant increase in the level of free iron in serum and tissues obtained from stages II-IV as compared to early-stage (stage I) ovarian cancer. There was an overlap between early-stage and inflammation serum MPO levels, however serum free iron levels were significantly higher in early-stage. There was no significant change in serum free iron levels between non-cancer groups. In contrast, there was a significant increase in serum free iron levels in early-stage as compared to non-cancer groups. Collectively, these findings clearly indicate a role for the combination of serum MPO and free iron as biomarkers for early detection and prognosis of ovarian cancer.


Disproportionation of Co2+ in the Topochemically Reduced Oxide LaSrCoRuO5.
Complex transition-metal oxides exhibit a wide variety of chemical and physical properties which are a strong function the local electronic states of the transition-metal centres, as determined by a combination of metal oxidation state and local coordination environment. Topochemical reduction of the double perovskite oxide, LaSrCoRuO6, using Zr, yields LaSrCoRuO5. This reduced phase contains an ordered array of apex-linked square-based pyramidal Ru3+O5, square-planar Co1+O4 and octahedral Co3+O6 units, consistent with the coordination-geometry driven disproportionation of Co2+. Coordination-geometry driven disproportionation of d7 transition-metal cations (e.g. Rh2+, Pd3+, Pt3+) is common in complex oxides containing 4d and 5d metals. However, the weak ligand field experienced by a 3d transition-metal such as cobalt leads to the expectation that d7+ Co2+ should be stable to disproportionation in oxide environments, so the presence of Co1+O4 and Co3+O6 units in LaSrCoRuO5 is surprising. Low-temperature measurements indicate LaSrCoRuO5 adopts a ferromagnetically ordered state below 120 K due to couplings between S = 1/2 Ru3+ and S = 1 Co1+.


The role of the RgpA-Kgp proteinase-adhesin complexes in the adherence of Porphyromonas gingivalis to fibroblasts.
Porphyromonas gingivalis strains W50 and ATCC 33277 were shown to bind to cultured human fibroblast (MRC-5) cells using flow cytometry. As the concentration of P. gingivalis strain W50 cells was increased relative to the concentration of MRC-5 cells, the number of W50 cells bound per MRC-5 cell increased, as did the percentage of MRC-5 cells with bacteria bound. However, this relationship was only seen for P. gingivalis strain ATCC 33277 at low cell concentrations: at high bacterial cell concentrations strain ATCC 33277 auto-aggregated and binding to the MRC-5 cells decreased. Strain W50 was therefore chosen to study the role of the surface proteinase-adhesin complexes (RgpA-Kgp complexes) in binding to MRC-5 cells. P. gingivalis W50 cells treated with an inhibitor of the RgpA-Kgp complexes exhibited reduced binding to MRC-5 cells. The purified active and proteinase-inactive RgpA-Kgp complexes competitively inhibited binding of W50 to MRC-5 cells, and isogenic mutants of W50 lacking RgpA/B and Kgp displayed reduced binding. P. gingivalis W50 mutant cells lacking Kgp exhibited the lowest binding to MRC-5 cells, suggesting an important role for this proteinase and its associated adhesins in binding to fibroblasts.


Ice caps on venus?
The data on Venus obtained by Mariner V and Venera 4 are interpreted as evidence of giant polar ice caps holding the water that must have come out of the volcanoes with the observed carbon dioxide, on the assumption that Earth and Venus are of similar composition and volcanic history. The measurements by Venera 4 of the equatorial surface temperature indicate that the microwave readings were high, so that the polar ice caps may be allowed to exist in the face of the 10-centimeter readings of polar temperature. Life seems to be distinctly possible at the edges of the ice sheets.


Overexpression of long noncoding RNA ANRIL inhibits phenotypic switching of vascular smooth muscle cells to prevent atherosclerotic plaque development in vivo.
Phenotypic switching of vascular smooth muscle cells (VSMCs) plays a key role in atherosclerosis. Long noncoding RNA ANRIL (lncRNA-ANRIL) is critical in vascular homeostasis. Metformin produces multiple beneficial effects in atherosclerosis. However, the underlying mechanisms need to be elucidated. Metformin increased lncRNA-ANRIL expression and AMPK activity in cultured VSMCs, and inhibited the phenotypic switching of VSMCs to the synthetic phenotype induced by platelet-derived growth factor (PDGF). Overexpression of lncRNA-ANRIL inhibited phenotypic switching and reversed the reduction of AMPK activity in PDGF-treated VSMCs. While, gene knockdown of lncRNA-ANRIL by adenovirus or silence of AMPKγ through siRNA abolished AMPK activation induced by metformin in VSMCs. RNA-immunoprecipitation analysis indicated that the affinity of lncRNA-ANRIL to AMPKγ subunit was increased by metformin. In vivo, administration of metformin increased the levels of lncRNA-ANRIL, suppressed VSMC phenotypic switching, and prevented the development of atherosclerotic plaque in Apoe-/- mice fed with western diet. These protective effects of metformin were abolished by infecting Apoe-/- mice with adenovirus expressing lncRNA-ANRIL shRNA. The levels of AMPK phosphorylation, AMPK activity, and lncRNA-ANRIL expression were decreased in human atherosclerotic lesions. Metformin activates AMPK to suppress the formation of atherosclerotic plaque through upregulation of lncRNA-ANRIL.


Molecular divergence defines two distinct lineages of Crithidia bombi (Trypanosomatidae), parasites of bumblebees.
This study provides, for the first time, sequence data for the protozoan flagellates Crithidia bombi and Crithidia mellificae (Kinetoplastea: Trypanosomatidae). We amplified the partial sequences of the small subunit ribosomal RNA (SSU rRNA), glycosomal glyceraldehyde phosphate dehydrogenase (gGAPDH), cytochrome b (Cyt b), and the complete internal transcribed spacer region 1 (ITS1) of the ribosomal RNA gene region for 66 clones of C. bombi from Switzerland and Alaska. Furthermore, we sequenced the same stretch of SSU rRNA and gGAPDH for one isolate of C. mellificae from Switzerland. All four molecular markers classified the C. bombi samples into two distinct lineages A and B. Both lineages were found in the two sampling locations. Variation within lineages was small or non-existing. Sequence differences between lineages were 1.64% for SSU rRNA, 4.36% for gGAPDH, and 12.02% for Cyt b. The ITS1-sequences of lineages A and B have diverged so much that no alignment was possible. With regard to ITS1, we additionally found fragment length polymorphism (variation in microsatellite repeat numbers) as well as nucleotide diversity within each lineage. Furthermore, the sequences of SSU rRNA and gGAPDH of C. mellificae were different from both lineages of C. bombi. The separation of lineages A and B, based on sequence differences and phylogenetic reconstruction, is so pronounced as to characterize two species of "C. bombi." We propose to retain C. bombi for the more common lineage A and suggest the name Crithidia expoeki n. sp. for lineage B.


A comparative assessment of the size of the frontal air sinus in the giraffe (Giraffa camelopardalis).
The current study examines the frontal air sinus of the giraffe (Giraffa camelopardalis) cranium with the aim of evaluating previously offered hypotheses as to why they have such an atypically voluminous frontal sinus relative to other artiodactyls. To date, no quantification of the frontal sinus in the adult or developing giraffe has been undertaken or compared to other artiodactyl species. Crania from eight species of adult artiodactyls, and giraffes varying in age from newborn to adult, were studied using CT scans to provide a volumetric assessment of the frontal sinus. Sinus volume was strongly correlated to cranial mass in the male giraffe ontogenetic series. The adult giraffe of both sexes were found to possess a far larger than predicted sinus volume relative to the relationship between frontal sinus volume and cranial mass observed in the other adult artiodactyls. Our results suggest that the volume of the frontal sinus in the giraffe is likely to be unique among artiodactyls, and the potential function and evolution we consider in light of several previously articulated hypotheses.


The STR120 satellite DNA of soybean: organization, evolution and chromosomal specificity.
A highly repeated DNA sequence family, STR120, with tandemly arranged repetitive units (monomers) of approximately 120bp, has been identified in soybean [Glycine max (L.) Merr.]. Five related clones showing tandem repeats of a 120-bp-long monomer were isolated from a soybean genomic library. Results of Southern blotting experiments using three of the clones as probes onto genomic DNA digested with different restriction enzymes were in agreement with a tandem arrangement of these sequences in the genome. A total of 12 monomers were sequenced, showing considerable sequence heterogeneity. A consensus sequence of 126 bp was obtained that exhibits an average similarity of 81% to the sequenced units. In three of the clones identified, neighbouring units are significantly more similar to each other than to units from different clones; in the remaining two clones, however, similarity between the two units observed is low (70%), while the overall similarity between the two clones is high (95%). This indicates that in these cases the repetitive unit may be the dimer rather than the monomer. Based on the presence of direct repeats within each monomer, we suggest that the 120-bp monomer may itself have evolved by duplication of an ancestral 60-bp unit. The STR120 family distribution is limited to annual soybeans and is not found, at least at high-copy number, in related perennial soybeans or other members of the tribe Phaseolae. Fluorescence in situ hybridization (FISH) to metaphase chromosomes using four of the clones as probes shows that the number of chromosomal locations differs depending on the stringency conditions and goes from two to eight when the stringency is progressively lowered. The estimated copy number for one of the clones is from 5000 to 10000, but this may just represent a lower boundary for the whole family in consideration of the high sequence divergence observed within the family. FISH and sequence analysis therefore indicate that different subfamilies as well as higher-order repeat units are present in the STR120 family, very much like those in primate alpha satellite DNA, and that some of the subfamilies seem to exhibit divergence on a chromosomal basis.


Continuous subcutaneous insulin infusion versus multiple daily injections in children and young people at diagnosis of type 1 diabetes: the SCIPI RCT.
The risk of developing long-term complications of type 1 diabetes (T1D) is related to glycaemic control and is reduced by the use of intensive insulin treatment regimens: multiple daily injections (MDI) (≥ 4) and continuous subcutaneous insulin infusion (CSII). Despite a lack of evidence that the more expensive treatment with CSII is superior to MDI, both treatments are used widely within the NHS. (1) To compare glycaemic control during treatment with CSII and MDI and (2) to determine safety and cost-effectiveness of the treatment, and quality of life (QoL) of the patients. A pragmatic, open-label randomised controlled trial with an internal pilot and 12-month follow-up with 1 : 1 web-based block randomisation stratified by age and centre. Fifteen diabetes clinics in hospitals in England and Wales. Patients aged 7 months to 15 years. Continuous subsutaneous insulin infusion or MDI initiated within 14 days of diagnosis of T1D. Data were collected at baseline and at 3, 6, 9 and 12 months using paper forms and were entered centrally. Data from glucometers and CSII were downloaded. The Health Utilities Index Mark 2 was completed at each visit and the Pediatric Quality of Life Inventory (PedsQL, diabetes module) was completed at 6 and 12 months. Costs were estimated from hospital patient administration system data. The primary outcome was glycosylated haemoglobin (HbA1c) concentration at 12 months. The secondary outcomes were (1) HbA1c concentrations of < 48 mmol/mol, (2) severe hypoglycaemia, (3) diabetic ketoacidosis (DKA), (4) T1D- or treatment-related adverse events (AEs), (5) change in body mass index and height standard deviation score, (6) insulin requirements, (7) QoL and (8) partial remission rate. The economic outcome was the incremental cost per quality-adjusted life-year (QALY) gained. A total of 293 participants, with a median age of 9.8 years (minimum 0.7 years, maximum 16 years), were randomised (CSII, n = 149; MDI, n = 144) between May 2011 and January 2015. Primary outcome data were available for 97% of participants (CSII, n = 143; MDI, n = 142). At 12 months, age-adjusted least mean squares HbA1c concentrations were comparable between groups: CSII, 60.9 mmol/mol [95% confidence interval (CI) 58.5 to 63.3 mmol/mol]; MDI, 58.5 mmol/mol (95% CI 56.1 to 60.9 mmol/mol); and the difference of CSII - MDI, 2.4 mmol/mol (95% CI -0.4 to 5.3 mmol/mol). For HbA1c concentrations of < 48 mmol/mol (CSII, 22/143 participants; MDI, 29/142 participants), the relative risk was 0.75 (95% CI 0.46 to 1.25), and for partial remission rates (CSII, 21/86 participants; MDI, 21/64), the relative risk was 0.74 (95% CI 0.45 to 1.24). The incidences of severe hypoglycaemia (CSII, 6/144; MDI, 2/149 participants) and DKA (CSII, 2/144 participants; MDI, 0/149 participants) were low. In total, 68 AEs (14 serious) were reported during CSII treatment and 25 AEs (eight serious) were reported during MDI treatment. Growth outcomes did not differ. The reported insulin use was higher with CSII (mean difference 0.1 unit/kg/day, 95% CI 0.0 to 0.2 unit/kg/day; p = 0.01). QoL was slightly higher for those randomised to CSII. From a NHS perspective, CSII was more expensive than MDI mean total cost (£1863, 95% CI £1620 to £2137) with no additional QALY gains (-0.006 QALYs, 95% CI -0.031 to 0.018 QALYs). Generalisability beyond 12 months is uncertain. No clinical benefit of CSII over MDI was identified. CSII is not a cost-effective treatment in patients representative of the study population. Longer-term follow-up is required to determine if clinical outcomes diverge after 1 year. A qualitative exploration of patient and professional experiences of MDI and CSII should be considered. Current Controlled Trials ISRCTN29255275 and EudraCT 2010-023792-25. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 42. See the NIHR Journals Library website for further project information. The cost of insulin pumps and consumables supplied by F. Hoffman-La Roche AG (Basel, Switzerland) for the purpose of the study were subject to a 25% discount on standard NHS costs.


The effect of dilution on plasma coagulation kinetics determined by thrombelastography is dependent on antithrombin activity and mode of activation.
Hemodilution-associated hypercoagulability has been the focus of several investigations because significant morbidity and mortality have been associated with perioperative thrombophilia. Because most investigations implicate imbalances in procoagulant/anticoagulant activity as the etiology of hemodilution-associated hypercoagulability, we determined the effects of dilution on coagulation kinetics and clot strength with thrombelastography (TEG(R)). Control plasma (+/-celite activation) and antithrombin (AT)-deficient (<10% activity) plasma were diluted 0%, 10%, 20%, and 30% with saline. TEG(R) variables measured included time to clot initiation (reaction time, R), speed of clot propagation (angle, alpha), and clot strength (amplitude, A; or shear elastic modulus, G). Dilution of control plasma (10%-30%) resulted in a significant (P < 0.05) 16% decrease in R values, no change in alpha values, and decrease in A and G values. AT-deficient plasma had significantly smaller R values compared with control, and dilution did not change R values in AT-deficient plasma. Celite activation eliminated dilution-associated changes in R values in control plasma but resulted in linear decreases (R(2) = 0.88-0.96, P < 0.0001) in alpha, A, and G in response to dilution. Thus, our data indirectly support the concept that decreases in AT activity cause dilution-mediated hypercoagulability in plasma. Finally, celite activation permits quantification of dilution with TEG.


Accurate measurement of 5-methylcytosine and 5-hydroxymethylcytosine in human cerebellum DNA by oxidative bisulfite on an array (OxBS-array).
The Infinium 450K Methylation array is an established tool for measuring methylation. However, the bisulfite (BS) reaction commonly used with the 450K array cannot distinguish between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). The oxidative-bisulfite assay disambiguates 5mC and 5hmC. We describe the use of oxBS in conjunction with the 450K array (oxBS-array) to analyse 5hmC/5mC in cerebellum DNA. The "methylation" level derived by the BS reaction is the combined level of 5mC and 5hmC at a given base, while the oxBS reaction gives the level of 5mC alone. The level of 5hmC is derived by subtracting the oxBS level from the BS level. Here we present an analysis method that distinguishes genuine positive levels of 5hmC at levels as low as 3%. We performed four replicates of the same sample of cerebellum and found a high level of reproducibility (average r for BS = 98.3, and average r for oxBS = 96.8). In total, 114,734 probes showed a significant positive measurement for 5hmC. The range at which we were able to distinguish 5hmC occupancy was between 3% and 42%. In order to investigate the effects of multiple replicates on 5hmC detection we also simulated fewer replicates and found that decreasing the number of replicates to two reduced the number of positive probes identified by > 50%. We validated our results using qPCR in conjunction with glucosylation of 5hmC sites followed by MspI digestion and we found good concordance with the array estimates (r = 0.94). This experiment provides a map of 5hmC in the cerebellum and a robust dataset for use as a standard in future 5hmC analyses. We also provide a novel method for validating the presence of 5hmC at low levels, and highlight some of the pitfalls associated with measuring 5hmC and 5mC.


Structure-Guided Discovery of Potent and Selective DYRK1A Inhibitors.
The kinase DYRK1A is an attractive target for drug discovery programs due to its implication in multiple diseases. Through a fragment screen, we identified a simple biaryl compound that is bound to the DYRK1A ATP site with very high efficiency, although with limited selectivity. Structure-guided optimization cycles enabled us to convert this fragment hit into potent and selective DYRK1A inhibitors. Exploiting the structural differences in DYRK1A and its close homologue DYRK2, we were able to fine-tune the selectivity of our inhibitors. Our best compounds potently inhibited DYRK1A in the cell culture and in vivo and demonstrated drug-like properties. The inhibition of DYRK1A in vivo translated into dose-dependent tumor growth inhibition in a model of ovarian carcinoma.


Citric acid does not improve phosphorus utilization in laying hens fed a corn-soybean meal diet.
Data previously obtained from our laboratory have indicated that citric acid was very effective at improving phytate-P utilization in chicks fed a P-deficient corn-soybean meal (SBM) diet. The objective of the current study was to determine if citric acid would have similar effects in a commercial strain of Single Comb White Leghorn laying hens (n = 432) fed a corn-SBM diet containing 0.10% available P (AP). Dietary treatments were a corn-SBM basal diet (0.10% AP, 3.8% Ca, and 17% CP) supplemented with 0, 1, 2, 3, or 4% citric acid and a positive control diet containing 0.45% AP. Each of the six dietary treatments were fed to six replicate groups of 12 hens from 22 to 40 wk of age. No significant differences in performance were observed among treatments during the first 4 wk of the experiment. Hen-day egg production, feed consumption, feed efficiency, and egg yield were subsequently depressed in hens fed 0, 1, 2, 3, or 4% citric acid compared with hens fed 0.45% AP. The results of this study indicate that citric acid does not improve the utilization of dietary P in laying hens fed a corn-SBM diet containing 3.8% Ca.


Evidence that laminin-5 is a component of the tooth surface internal basal lamina, supporting epithelial cell adhesion.
Laminin-5 (Ln-5) is an extracellular matrix (ECM) glycoprotein found in epithelial basal laminae. We studied its expression on the surface of rat molars, in relationship to the location of the internal basal lamina (IBL) of the junctional epithelium (JE). In order to avoid disruption of the JE-tooth interface as much as possible, the surface of molars was prepared by mechanical removal of tissue debris and detergent/osmotic lysis of epithelial cell layers, and directly stained by immunohistochemistry, without sectioning. Antibodies to Ln-5 specifically stained a narrow band in the region of the cemento-enamel junction (CEJ), consistent with the expected location of the IBL. Western blotting of ECM material detergent--solubilized from the prepared tooth surfaces confirmed the molecular nature of Ln-5 identified by immunohistochemistry. By the use of a high-definition 3-D microscope, it appeared that Ln-5 coated the most apical part of the enamel and the most coronal portion of the cementum, on either side of the CEJ. In adhesion assays performed directly on tooth surfaces, epithelial cells adhered preferentially to the Ln-5 coated area of the tooth compared to the root surface, which is coated by other ECM components. Adhesion to the Ln-5 coated surface was specifically inhibited by a function-blocking monoclonal antibody to Ln-5. These results suggest that Ln-5 is a component of the IBL, and that it may be important in promoting adhesion of JE cells onto the tooth surface.


[Nutritional status of schoolchildren of the National Child and Youth Education Teaching Network of the Social Service of Commerce (Sesc), Brazil, 2012].
The objective of this study was to identify and describe the growth and nutritional anthropometric profile of children enrolled in the Sesc National Network of Elementary Education. It is a cross-sectional study conducted among 20,113 students (9,992 girls) from 83 schools aged from 3 to 17. Nutritional status was determined using the body mass index for age and stature for age according to the WHO criteria. Stunting was observed in only 1.6% (girls) and 1.3% (boys). Overweight + obesity was observed in 29.7% of the schoolchildren (27.6% of girls and 32.3% of boys). In the < 5y schoolchildren, BMI was equal to 12.3% (10.9% of girls and 13.2% of boys). In the 5-10y group, the prevalence was 35.3% in girls and 40.1% in boys (37.8% in all). In the 10y+ group, there were 32.5% (girls) and 43.0% (boys), 37.4% overall. The identified prevalences of BMI in all age groups were high and the problem worsens in older children and in boys. These findings corroborate the reported situation in national and international studies and reinforce the need for monitoring and intervening in the nutritional status of schoolchildren.


Role of Pre-Operative Nutrition Status on Surgical Site Infection After Posterior Lumbar Interbody Fusion: A Retrospective Study.
Background: A retrospective case-control study to determine the role of pre-operative systemic and local nutritional factors on patients developing a surgical site infection (SSI) after posterior lumbar interbody fusion (PLIF). Surgical site infection after PLIF remains a substantial cause of morbidity. The literature demonstrates the prognosis of surgical patients is associated with pre-operative nutritional status that not only includes systemic nutritional factors, such as prognostic nutritional index (PNI), body mass index (BMI), and serum albumin, but also local nutritional factors, such as subcutaneous fat thickness at the surgical site, including absolute fat thickness and relative fat thickness. However, the role of pre-operative nutrition status in SSI after PLIF surgery remains unclear. Patients and Method: A retrospective review was performed on a consecutive cohort of 766 consecutive adult patients who underwent PLIF surgery for lumbar degenerative conditions between 2020 and 2021 at Second Xiangya Hospital. Previously identified risk factors as well as systemic and local nutritional factors nutritional factors were collected. Results: Among the 766 patients, 38 had post-operative SSI including 15 superficial SSI and 23 deep SSI. Univariable analysis showed that body weight, BMI, PNI, serum albumin, and relative fat thickness differed between the SSI and non-SSI groups. Multivariable logistic regression analysis showed that pre-operative PNI and relative fat thickness were independently associated with SSI after PLIF surgery. Conclusions: Lower pre-operative PNI and higher relative fat thickness are independent risk factors for developing deep SSI after PLIF.


Care fragmentation and emergency department use among complex patients with diabetes.
To evaluate the association between patterns of fragmented care and emergency department (ED) use among adult patients with diabetes and chronic kidney disease. Observational study in an open healthcare system. The study sample included patients with diabetes and chronic kidney disease (mean estimated glomerular filtration rate, 20-60 mL/min) and with an established primary care provider. Dispersion of care was defined by a fragmentation of care index (range, 0-1), with zero reflecting all care in 1 outpatient clinic and 1 reflecting each visit at a different clinic site. We used a negative binomial model to estimate the influence of fragmentation on ED use after adjusting for patient demographic characteristics, insurance, diabetes control, and number of comorbidities; results are reported as incidence rate ratios and associated 95% confidence intervals (CIs). The main outcome measure was the number of ED visits from 2002 to 2003. Of 3873 patients with diabetes having an established primary care provider, 623 (16.1%) had chronic kidney disease and comprised the final study sample. On average, patients made 19.0 (95% CI, 18.5-20.4) outpatient visits and 1.2 (95% CI, 1.1-1.4) ED visits over the 2-year period. The median fragmentation of care index was 0.48; 14.3% of subjects had a fragmentation of care index of zero. In the adjusted model, a 0.1-U increase in the fragmentation of care index was associated with a 15% increase in the number of ED visits (incidence rate ratio, 1.15; 95% CI, 1.09-1.21). The posited benefits of specialist referrals among patients with complex diabetes may be partially negated by care fragmentation. Better models for care coordination and stronger evidence of the marginal benefits of referrals are needed.


Results of a fatigue management programme in multiple sclerosis.
Fatigue in patients with multiple sclerosis (MS) is a complex symptom that is notoriously difficult to treat, not least because it is extremely subjective and is experienced differently by each patient. Owing to the prevalence of this symptom, most patients with MS who are seen in outpatient settings complain of fatigue and experience the disabling effect it can have upon day-to-day living. Managing and treating this symptom is a challenge, although there is some evidence that applying fatigue management principles can potentially reduce the debilitating effect fatigue has on patients (Welham, 1995). This article reviews the evidence base surrounding the management and treatment of fatigue that is applied in clinical practice. It describes the fatigue management programme that had been introduced for people with MS at the authors' workplace, and evaluated whether applying fatigue management principles can make a difference to people's ability to self-care. The effect this symptom has upon people's quality of life will also be explored.


Simple models for containment of a pandemic.
Stochastic simulations of network models have become the standard approach to studying epidemics. We show that many of the predictions of these models can also be obtained from simple classical deterministic compartmental models. We suggest that simple models may be a better way to plan for a threatening pandemic with location and parameters as yet unknown, reserving more detailed network models for disease outbreaks already underway in localities where the social networks are well identified.We formulate compartmental models to describe outbreaks of influenza and attempt to manage a disease outbreak by vaccination or antiviral treatment. The models give an important prediction that may not have been noticed in other models, namely that the number of doses of antiviral treatment required is extremely sensitive to the number of initial infectives. This suggests that the actual number of doses needed cannot be estimated with any degree of reliability. The model is applicable to pre-epidemic vaccination, such as annual vaccination programs in anticipation of an 'ordinary' influenza outbreak with limited drift, and as a combination of treatment both before and during an epidemic.


CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling.
Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The hrs/actinin-4/BERP/myosin V (CART [cytoskeleton-associated recycling or transport]) complex assembles in a linear manner and interrupting binding of any member to its neighbor produces an inhibition of transferrin recycling rate. Disrupting the CART complex results in shunting receptors to a slower recycling pathway that involves the recycling endosome. The novel CART complex may provide a molecular mechanism for the actin-dependence of rapid recycling of constitutively recycled plasma membrane receptors.


Dynamical Boolean Modeling of Immunogenic Cell Death.
As opposed to the standard tolerogenic apoptosis, immunogenic cell death (ICD) constitutes a type of cellular demise that elicits an adaptive immune response. ICD has been characterized in malignant cells following cytotoxic interventions, such as chemotherapy or radiotherapy. Briefly, ICD of cancer cells releases some stress/danger signals that attract and activate dendritic cells (DCs). The latter can then engulf and cross-present tumor antigens to T lymphocytes, thus priming a cancer-specific immunity. This series of reactions works as a positive feedback loop where the antitumor immunity further improves the therapeutic efficacy by targeting cancer cells spared by the cytotoxic agent. However, not all chemotherapeutic drugs currently approved for cancer treatment are able to stimulate bona fide ICD: some commonly used agents, such as cisplatin or 5-fluorouracil, are unable to activate all features of ICD. Therefore, a better characterization of the process could help identify some gene or protein candidates to target pharmacologically and suggest combinations of drugs that would favor/increase antitumor immune response. To this end, we have built a mathematical model of the major cell types that intervene in ICD, namely cancer cells, DCs, CD8+ and CD4+ T cells. Our model not only integrates intracellular mechanisms within each individual cell entity, but also incorporates intercellular communications between them. The resulting cell population model recapitulates key features of the dynamics of ICD after an initial treatment, in particular the time-dependent size of the different cell types. The model is based on a discrete Boolean formalism and is simulated by means of a software tool, UPMaBoSS, which performs stochastic simulations with continuous time, considering the dynamics of the system at the cell population level with appropriate timing of events, and accounting for death and division of each cell type. With this model, the time scales of some of the processes involved in ICD, which are challenging to measure experimentally, have been predicted. In addition, our model analysis led to the identification of actionable targets for boosting ICD-induced antitumor response. All computational analyses and results are compiled in interactive notebooks which cover the presentation of the network structure, model simulations, and parameter sensitivity analyses.


[Specific latex preparations in the etiological diagnosis of suppurative bacterial meningitis].
The results of the evaluation of the diagnostic latex preparations Bactigen, manufactured by Wampole Laboratories (USA) and intended for the detection of meningococcal antigens, serogropus A, B, C, Y, pneumococcal polyantigens and type b Haemophilus influenzae antigens in the spinal fluid and blood of patients with meningococcal infection and purulent bacterial meningitides, are presented. The pathological material was studied by traditional methods and by the latex agglutination (LAG) test. 522 LAG tests were made, including 414 tests for meningococcal infection, 60 tests for pneumococcal infection and 48 tests for type b H. influenzae. The results of this study revealed that the latex preparations were highly specific with respect to type b H. influenzae antigens and meningococcal antigens (false positive reactions constituted 0.96%). The simplicity of the test and the rapid techniques making it possible to obtain results within 30-40 minutes indicate good prospects of using the LAG test in laboratory practice.


Class H diabetes and pregnancy.
Class H diabetes is defined as the presence of diabetes of any duration associated with ischemic myocardial disease. Because of a lack of experience with the coexistence of myocardial ischemic disease and diabetes during pregnancy, it is difficult to offer patients an accurate prognosis for mother and infant during such a gestation. Previous reports suggest that outcomes in this situation are almost routinely poor. It is likely, however, that there is a subset of patients within the class H diabetic population in whom pregnancy can be successful. Reported are the pregnancies of three such patients. The authors suggest that careful attention to cardiac status and glycemic control contribute to both maternal and fetal well-being. Prepregnancy screening of class H patients for evidence of cardiac dysfunction may allow for the screening of those class H diabetic women who are most likely to achieve successful pregnancy outcome.


The neural substrates of religious experience.
Religious experience is brain-based, like all human experience. Clues to the neural substrates of religious-numinous experience may be gleaned from temporolimbic epilepsy, near-death experiences, and hallucinogen ingestion. These brain disorders and conditions may produce depersonalization, derealization, ecstasy, a sense of timelessness and spacelessness, and other experiences that foster religious-numinous interpretation. Religious delusions are an important subtype of delusional experience in schizophrenia, and mood-congruent religious delusions are a feature of mania and depression. The authors suggest a limbic marker hypothesis for religious-mystical experience. The temporolimbic system tags certain encounters with external or internal stimuli as depersonalized, derealized, crucially important, harmonious, and/or joyous, prompting comprehension of these experiences within a religious framework.


Preoperative ultrasound is worthwhile for reoperative parathyroid surgery.
High-resolution ultrasound and sestamibi scanning are regarded as the first-line methods for preoperative localization of parathyroid adenomas. The utility of ultrasound in reoperative cases has been questioned because of concern that scarring will obscure normal tissue planes and vascularity that are critical to identification of an adenoma using this imaging modality. The purposes of the study were to evaluate the ability of high-resolution ultrasound to accurately localize parathyroid adenomas in the reoperative exploration and to identify any factors that influence its accuracy Retrospective chart review at a tertiary care academic medical center. All patients seen in referral for parathyroid surgery between May 1994 and September 2002 underwent high-resolution ultrasound as their initial diagnostic test. Patients who subsequently underwent exploration were included in the study. Intraoperative and ultrasound findings were compared. One hundred forty-two patients were included, 116 without and 26 with prior exploration. The sensitivity and positive predictive value of ultrasound were 86.9% and 89.1%, respectively. These data were not significantly different in patients without (88.2% and 90%) and in patients with (80% and 84.2%) prior thyroid or parathyroid surgery. The overall accuracy was 79% with a false-negative rate of 11.3%. Thyroid nodularity was significantly more common (81.8%) in patients who had a false-positive or false-negative finding on ultrasound than in the total population (61.3%). High-resolution ultrasound is an accurate method for localizing parathyroid adenomas even in patients who have previously undergone parathyroid exploration. However, the presence of thyroid nodules can interfere with its accuracy.


Spectrum of leprosy among suspected cases attending a teaching hospital in Western Rajasthan, India.
Leprosy is a chronic granulomatous infectious disease, which mainly involves skin, peripheral nerves, mucosa of the upper respiratory tract, and eyes. According to National Leprosy Eradication Programme 2017-18 annual report, the annual new case detection rate from Rajasthan is 1.27 per 1 lakh population and prevalence rate is 0.14. The main objective of this study was to determine the spectrum of Mycobacterium leprae infections among suspected cases attending a teaching hospital in western Rajasthan, India. This is a retrospective study conducted in the Department of Microbiology, in a teaching hospital, western Rajasthan, between the period of January 2017 and April 2019. The records of modified Ziehl-Neelsen staining during the study period were analyzed. The demographic data like age and sex along with clinical diagnosis were also recorded from laboratory register and hospital information system. Out of total 91 suspected cases, 30.77% was microbiologically confirmed cases of leprosy. Out of total positive cases, 71.43% were male and 28.57% were female. A maximum number of positive (50%) were found in the age group of 31-50 years. Present study gives an insight about the spectrum of leprosy in the region. The large number of positive cases signifies that leprosy awareness and programs aimed at elimination need to be more vigorously implemented. To achieve complete eradication from this menace, newer strategies like effective vaccine development and drug-resistance testing should be implemented.


Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes.
Previous studies had shown that the integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP), a reference resource population for cardiovascular and metabolic traits. We report numerous novel transcripts supported by proteomic analyses, as well as novel non coding RNAs. High resolution genetic mapping of transcript levels in HMDP, reveals both local and trans expression Quantitative Trait Loci (eQTLs) demonstrating 2 trans eQTL 'hotspots' associated with expression of hundreds of genes. We also report thousands of alternative splicing events regulated by genetic variants. Finally, comparison with about 150 metabolic and cardiovascular traits revealed many highly significant associations. Our data provide a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation.


Frequency dependence of specific heat in supercooled liquid water and emergence of correlated dynamics.
Molecular origin of the well-known specific heat anomaly in supercooled liquid water is investigated here by using extensive computer simulations and theoretical analyses. A rather sharp increase in the values of isobaric specific heat with lowering temperature and the weak temperature dependence of isochoric specific heat in the same range are reproduced in simulations. We calculated the spatio-temporal correlation among temperature fluctuations and examined the frequency dependent specific heat. The latter shows a rapid growth in the low frequency regime as temperature is cooled below 270 K. In order to understand the microscopic basis of this increase, we have performed a shellwise decomposition of contributions of distant molecules to the temperature fluctuations in a central molecule. This decomposition reveals the emergence, at low temperatures, of temporally slow, spatially long ranged large temperature fluctuations. The temperature fluctuation time correlation function (TFCF) can be fitted to a William-Watts stretched exponential form with the stretching parameter close to 0.6 at low temperatures, indicating highly non-exponential relaxation. Temperature dependence of the relaxation time of the correlation function can be fitted to Vogel-Fulcher-Tamermann expression which provides a quantitative measure of the fragility of the liquid. Interestingly, we find that the rapid growth in the relaxation time of TFCF with lowering temperature undergoes a sharp crossover from a markedly fragile state to a weakly fragile state around 220 K.


Based on T-spherical fuzzy environment: A combination of FWZIC and FDOSM for prioritising COVID-19 vaccine dose recipients.
The problem complexity of multi-criteria decision-making (MCDM) has been raised in the distribution of coronavirus disease 2019 (COVID-19) vaccines, which required solid and robust MCDM methods. Compared with other MCDM methods, the fuzzy-weighted zero-inconsistency (FWZIC) method and fuzzy decision by opinion score method (FDOSM) have demonstrated their solidity in solving different MCDM challenges. However, the fuzzy sets used in these methods have neglected the refusal concept and limited the restrictions on their constants. To end this, considering the advantage of the T-spherical fuzzy sets (T-SFSs) in handling the uncertainty in the data and obtaining information with more degree of freedom, this study has extended FWZIC and FDOSM methods into the T-SFSs environment (called T-SFWZIC and T-SFDOSM) to be used in the distribution of COVID-19 vaccines. The methodology was formulated on the basis of decision matrix adoption and development phases. The first phase described the adopted decision matrix used in the COVID-19 vaccine distribution. The second phase presented the sequential formulation steps of T-SFWZIC used for weighting the distribution criteria followed by T-SFDOSM utilised for prioritising the vaccine recipients. Results revealed the following: (1) T-SFWZIC effectively weighted the vaccine distribution criteria based on several parameters including T = 2, T = 4, T = 6, T = 8, and T = 10. Amongst all parameters, the age criterion received the highest weight, whereas the geographic locations severity criterion has the lowest weight. (2) According to the T parameters, a considerable variance has occurred on the vaccine recipient orders, indicating that the existence of T values affected the vaccine distribution. (3) In the individual context of T-SFDOSM, no unique prioritisation was observed based on the obtained opinions of each expert. (4) The group context of T-SFDOSM used in the prioritisation of vaccine recipients was considered the final distribution result as it unified the differences found in an individual context. The evaluation was performed based on systematic ranking assessment and sensitivity analysis. This evaluation showed that the prioritisation results based on each T parameter were subject to a systematic ranking that is supported by high correlation results over all discussed scenarios of changing criteria weights values.


A nanostructured graphene/polyaniline hybrid material for supercapacitors.
A flexible graphene/polyaniline hybrid material as a supercapacitor electrode was synthesized by an in situ polymerization-reduction/dedoping-redoping process. This product was first prepared in an ethylene glycol medium, then treated with hot sodium hydroxide solution to obtain the reduced graphene oxide/polyaniline hybrid material. Sodium hydroxide also acted as a dedoping reagent for polyaniline in the composite. After redoping in an acidic solution, the thin, uniform and flexible conducting graphene/polyaniline product was obtained with unchanged morphology. The chemical structure of the materials was characterized by X-ray photoelectron spectroscopy and Raman spectroscopy. The composite material showed better electrochemical performances than the pure individual components. A high specific capacitance of 1126 F g(-1) was obtained with a retention life of 84% after 1000 cycles for supercapacitors. The energy density and power density were also better than those of pure component materials.


In vitro resistance selections for Plasmodium falciparum dihydroorotate dehydrogenase inhibitors give mutants with multiple point mutations in the drug-binding site and altered growth.
Malaria is a preventable and treatable disease; yet half of the world's population lives at risk of infection, and an estimated 660,000 people die of malaria-related causes every year. Rising drug resistance threatens to make malaria untreatable, necessitating both the discovery of new antimalarial agents and the development of strategies to identify and suppress the emergence and spread of drug resistance. We focused on in-development dihydroorotate dehydrogenase (DHODH) inhibitors. Characterizing resistance pathways for antimalarial agents not yet in clinical use will increase our understanding of the potential for resistance. We identified resistance mechanisms of Plasmodium falciparum (Pf) DHODH inhibitors via in vitro resistance selections. We found 11 point mutations in the PfDHODH target. Target gene amplification and unknown mechanisms also contributed to resistance, albeit to a lesser extent. These mutant parasites were often hypersensitive to other PfDHODH inhibitors, which immediately suggested a novel combination therapy approach to preventing resistance. Indeed, a combination of wild-type and mutant-type selective inhibitors led to resistance far less often than either drug alone. The effects of point mutations in PfDHODH were corroborated with purified recombinant wild-type and mutant-type PfDHODH proteins, which showed the same trends in drug response as the cognate cell lines. Comparative growth assays demonstrated that two mutant parasites grew less robustly than their wild-type parent, and the purified protein of those mutants showed a decrease in catalytic efficiency, thereby suggesting a reason for the diminished growth rate. Co-crystallography of PfDHODH with three inhibitors suggested that hydrophobic interactions are important for drug binding and selectivity.


Nonstatistical dynamics on the caldera.
We explore both classical and quantum dynamics of a model potential exhibiting a caldera: that is, a shallow potential well with two pairs of symmetry related index one saddles associated with entrance/exit channels. Classical trajectory simulations at several different energies confirm the existence of the "dynamical matching" phenomenon originally proposed by Carpenter, where the momentum direction associated with an incoming trajectory initiated at a high energy saddle point determines to a considerable extent the outcome of the reaction (passage through the diametrically opposing exit channel). By studying a "stretched" version of the caldera model, we have uncovered a generalized dynamical matching: bundles of trajectories can reflect off a hard potential wall so as to end up exiting predominantly through the transition state opposite the reflection point. We also investigate the effects of dissipation on the classical dynamics. In addition to classical trajectory studies, we examine the dynamics of quantum wave packets on the caldera potential (stretched and unstretched). These computations reveal a quantum mechanical analogue of the "dynamical matching" phenomenon, where the initial expectation value of the momentum direction for the wave packet determines the exit channel through which most of the probability density passes to product.


Lumbosacral chordoma. Prognostic factors and treatment.
Retrospective analysis. To analyze the prognostic factors in patients with chordomas, the success of various treatments, the diagnostic value of open versus needle biopsy, the neurologic impairment after sacral nerve resection, and the clinical presentation and site of origin. Staging of chordomas has not been of much value, compared with other bone tumors, because for chordomas, grade is similar, metastasis is infrequent at presentation, and the prognostic significance of size is uncertain. A review of patients with chordoma from 1965 through 1996 found 23 cases (mean age of patients, 55 years). The mean follow-up was 84 months. Mean tumor size was 81 mm (range, 35-135 mm), location was lumbar (n = 6), S1 (n = 4), S2 (n = 3), S3 (n = 7), S4 (n = 2), and S5 (n = 1). No tumors were found in the higher sacrum (S1-S2) alone, without involvement of the lower sacrum. Survival analysis at 5 years showed overall survival (OS) 86%, continuous disease-free survival (CDFS) 58%, and local recurrence-free survival (LRFS) 60%. The location of tumor, defined by highest level of involvement (lumbar vs. sacrum) was of prognostic significance for OS (P = 0.01; log-rank test), CDFS (P = 0.036), but not for LRFS (P = 0.189). Results of multivariate regression showed that location was significant for OS (P = 0.007), CDFS (P = 0.008), and LRFS (P = 0.001). For patients with positive margins (n = 16), initial radiation correlated with longer CDFS (P = 0.002; Mantel-Cox) and LRFS (P = 0.005, Mantel-Cox), but was not significant for OS (P = 0.41). For patients who received no radiation, a positive margin correlated with a shorter CDFS (P = 0.04), a trend to shorter LRFS (P = 0.08), but no difference in OS. Therefore, both a tumor-free margin and initial radiation correlated with a longer survival. No patients had urinary or bowel dysfunction when both S3 nerves were preserved. If one S3 nerve was preserved, 1 of 3 patients had partial urinary incontinence and 2 of 3 patients required bowel medications. If both S3 nerves were resected, all patients required intermittent urinary catheterization and bowel medications. If both S2 nerves were resected, there was complete urinary and bowel incontinence. The highest level of tumor involvement was prognostically significant for OS, CDFS, and LRFS. Radiation was of value when complete excision was not achieved. Bilateral S3 nerve preservation is necessary to ensure retention of normal urinary and bowel function.


Nightly sublingual tizanidine HCl in multiple sclerosis: clinical efficacy and safety.
Approximately 90% of patients with multiple sclerosis (MS) experience spasticity during their lifetime. Tizanidine HCl is an alpha2 adrenergic agonist indicated for treating spasticity due to MS or spinal cord injury. To compare the clinical efficacy and safety of once-nightly sublingual versus oral tizanidine HCl (8 mg) or placebo in MS patients with spasticity requiring treatment. A double-blind, double-dummy, randomized, 3-treatment, 2-way crossover, comparative, placebo-controlled study was conducted in a neuroimmunology clinic of a university-affiliated medical center (December 2005 to March 2006). Enrolled patients received placebo once nightly and were then randomized to receive oral tizanidine HCl following sublingual tizanidine HCl or sublingual tizanidine HCl following oral tizanidine HCl, each arm for 7 days. The patients were evaluated for spasticity (Ashworth scale), mobility, Global Assessments of Disease Severity and Change, and safety parameters, including next-day somnolence (Epworth Sleepiness Scale), fatigue, hypotension, and hepatotoxicity. Sixteen MS patients aged 20 to 65 years with spasticity requiring treatment and Expanded Disability Status Scale score of 6.5 or less were enrolled. There were significant reductions in next-day (12-14 hours after dosing) spasticity following sublingual tizanidine compared with placebo and oral tizanidine, oral versus placebo treatment, and sublingual tizanidine versus placebo treatment. Fatigue, hypotension, or hepatotoxicity levels did not increase. Overnight sublingual tizanidine provides improvement in next-day spasticity compared with placebo, without increasing next-day somnolence. The Epworth somnolence score improved significantly with sublingual tizanidine treatment. This is contrary to the reported day-dose tizanidine use, in which increased somnolence is the most cited cause for patient dissatisfaction and noncompliance.


Multistage Self-Assembled Nanomaterials for Cancer Immunotherapy.
Advances in nanotechnology have brought innovations to cancer therapy. Nanoparticle-based anticancer drugs have achieved great success from bench to bedside. However, insufficient therapy efficacy due to various physiological barriers in the body remains a key challenge. To overcome these biological barriers and improve the therapeutic efficacy of cancers, multistage self-assembled nanomaterials with advantages of stimuli-responsiveness, programmable delivery, and immune modulations provide great opportunities. In this review, we describe the typical biological barriers for nanomedicines, discuss the recent achievements of multistage self-assembled nanomaterials for stimuli-responsive drug delivery, highlighting the programmable delivery nanomaterials, in situ transformable self-assembled nanomaterials, and immune-reprogramming nanomaterials. Ultimately, we perspective the future opportunities and challenges of multistage self-assembled nanomaterials for cancer immunotherapy.


Support Vector Machine Weather Prediction Technology Based on the Improved Quantum Optimization Algorithm.
Emotion recognition is a research hotspot in the field of artificial intelligence. If the human-computer interaction system can sense human emotion and express emotion, it will make the interaction between the robot and human more natural. In this paper, a multimodal emotion recognition model based on many-objective optimization algorithm is proposed for the first time. The model integrates voice information and facial information and can simultaneously optimize the accuracy and uniformity of recognition. This paper compares the emotion recognition algorithm based on many-objective algorithm optimization with the single-modal emotion recognition model proposed in this paper and the ISMS_ALA model proposed by recent related research. The experimental results show that compared with the single-mode emotion recognition, the proposed model has a great improvement in each evaluation index. At the same time, the accuracy of emotion recognition is 2.88% higher than that of the ISMS_ALA model. The experimental results show that the many-objective optimization algorithm can effectively improve the performance of the multimodal emotion recognition model.


Prostatic ductal system in rats: regional variation in stromal organization.
The rat prostate is composed of a complex system of branching ducts which terminate proximally at the urethra. It has been recognized that epithelial cells lining the ducts respond differently to androgen in various regions of the ducts, with responses ranging from proliferation to apoptosis, but the cellular mechanisms underlying these effects are unclear. Interaction between prostatic stroma and epithelium is essential to normal prostate growth and development, and the prostatic stroma is thought to be the first site of androgen action. Therefore we have examined the organization and distribution of stromal cell types along the rat prostatic ductal system. Using immunohistochemical techniques, we observed abundant fibrous tissue surrounding the distal region of the ducts, with a sparse, discontinuous smooth muscle layer. The intermediate region was surrounded by a continuous layers of smooth muscle one to two cells thick, which increased to greater than four layers thick at the proximal region. Fibrous tissue was located in interductal spaces and occasionally interspersed within the muscle layers in both regions. These observations indicate that regional variations in the distribution of stromal cell types exist and suggest that their corresponding secretory products could be responsible for the various effects of androgen on the epithelium in the rat prostatic ductal system.


Latent TB infection in newly diagnosed lung cancer patients - A multicenter prospective observational study.
Lung cancer and tuberculosis (TB) share common risk factors and are associated with high morbidity and mortality. Coexistence of lung cancer and TB were reported in previous studies, with uncertain pathogenesis. The association between lung cancer and latent TB infection (LTBI) remains to be explored. Newly diagnosed, treatment-naïve lung cancer patients were prospectively enrolled from four referral medical centers in Taiwan. The presence of LTBI was determined by QuantiFERON-TB Gold In-Tube (QFT-GIT). Demographic characteristics and cancer-related factors associated with LTBI were investigated. The survival status was also analyzed according to the status of LTBI. A total of 340 lung cancer patients were enrolled, including 96 (28.2%) LTBI, 214 (62.9%) non-LTBI, and 30 (8.8%) QFT-GIT results-indeterminate cases. Non-adenocarcinoma cases had higher proportion of LTBI than those of adenocarcinoma, especially in patients with younger age. In multivariate analysis, COPD (OR 2.41, 95% CI 1.25-4.64), fibrocalcified lesions on chest radiogram (OR 2.73, 95% CI 1.45-5.11), and main tumor located in typical TB areas (OR 2.02, 95% CI 1.15-3.55) were independent clinical predictors for LTBI. Kaplan-Meier survival analysis demonstrated patients with indeterminate QFT-GIT results had significantly higher 1-year all-cause mortality than those with LTBI (p<0.001) and non-LTBI (p=0.003). In multivariate analysis, independent predictors for 1-year all-cause mortality included BMI<18.5 (HR 2.09, 95% CI 1.06-4.14, p=0.033), advanced stage of lung cancer (RR 7.76, 95% CI 1.90-31.78, p=0.004), and indeterminate QFT-GIT results (RR 2.40, 95% CI 1.27-4.54, p=0.007). More than one-quarter of newly diagnosed lung cancer patients in Taiwan have LTBI. The independent predictors for LTBI include COPD, fibrocalcified lesions on chest radiogram, and main tumor located in typical TB areas. The survival rate is comparable between LTBI and non-LTBI cases. However, indeterminate QFT-GIT result was an independent predictor for all-cause mortality in lung cancer patients.


Using host traits to predict reservoir host species of rabies virus.
Wildlife are important reservoirs for many pathogens, yet the role that different species play in pathogen maintenance frequently remains unknown. This is the case for rabies, a viral disease of mammals. While Carnivora (carnivores) and Chiroptera (bats) are the canonical mammalian orders known to be responsible for the maintenance and onward transmission of rabies Lyssavirus (RABV), the role of most species within these orders remains unknown and is continually changing as a result of contemporary host shifting. We combined a trait-based analytical approach with gradient boosting machine learning models to identify physiological and ecological host features associated with being a reservoir for RABV. We then used a cooperative game theory approach to determine species-specific traits associated with known RABV reservoirs. Being a carnivore reservoir for RABV was associated with phylogenetic similarity to known RABV reservoirs, along with other traits such as having larger litters and earlier sexual maturity. For bats, location in the Americas and geographic range were the most important predictors of RABV reservoir status, along with having a large litter. Our models identified 44 carnivore and 34 bat species that are currently not recognized as RABV reservoirs, but that have trait profiles suggesting their capacity to be or become reservoirs. Further, our findings suggest that potential reservoir species among bats and carnivores occur both within and outside of areas with current RABV circulation. These results show the ability of a trait-based approach to detect potential reservoirs of infection and could inform rabies control programs and surveillance efforts by identifying the types of species and traits that facilitate RABV maintenance and transmission.


Visceral artery aneurysm rupture.
Aneurysms of the visceral arteries are infrequently encountered. Many are found incidentally and are thought to have a benign outcome. To better characterize these lesions and their clinical course, we reviewed our experience with visceral artery aneurysms (VAAs) at a single institution. A retrospective analysis of all VAAs diagnosed at our institution over the past 10 years was performed. The presentation, management, and outcome of therapy was examined for each patient. Thirty-four VAAs in 26 patients were diagnosed over the past 10 years. Four patients had multiple VAAs: splenic (17), hepatic (7), celiac (3), superior mesenteric (2), gastroduodenal (2), pancreaticoduodenal (1), right gastric (1), ileal (1) artery aneurysms. Associated aneurysms were found in 31% of patients and involved the thoracic aorta (3 patients), abdominal aorta (4 patients), renal arteries (2 patients), iliac artery (3 patients), lower extremity (1 patient), and intracranium (1 patient). In 15 patients (58%), VAAs were detected before rupture by chance or because abdominal symptoms resulted in diagnostic evaluation. Eight of these underwent elective surgery, and there were no deaths. Of those 15 patients with known VAAs, one patient died of rupture and hemorrhage from an untreated splenic artery aneurysm. Eleven patients (42%) presented unexpectedly with rupture, and two died despite prompt surgical treatment. The mortality rate in patients who had ruptured VAAs was 25%, including those who presented with ruptured aneurysms and those observed whose aneurysms eventually ruptured. Aneurysms of the visceral arteries are rare but important vascular lesions. Associated aneurysms are common. Because of the risk of rupture, often with a fatal outcome, an aggressive approach to the treatment of VAA is essential.