Clinical strategies for the primary health care professional to minimize prescription opioid abuse.
Prescription opioid analgesic therapy can be effective in managing chronic noncancer pain in appropriately selected patients. However, the risks and benefits of prescription opioids should be carefully considered when treating this patient population. A dramatic increase in opioid-related morbidity and mortality has been observed in the United States in the past decade. Therefore, health care providers must balance the treatment of chronic pain with the need to minimize the risks of opioid misuse, abuse, addiction, and diversion. Current literature suggests that most patients with chronic pain are managed at the primary care level. However, many of these practitioners are not skilled in risk assessment, stratification, and monitoring. This article reviews strategies and tools that providers may implement to help identify appropriate patients for chronic opioid therapy and recognize signs of drug-related aberrant behaviors and abuse. In addition, the potential role of abuse-deterrent, extended-release opioid formulations to reduce risk in patients and nonmedical users of opioids is introduced. Collectively, these preventative measures may effectively reduce opioid misuse, abuse, and diversion without denying adequate analgesia in appropriate patients.


On the Processing of "Extinguished" Stimuli in Unilateral Visual Neglect: An Approach Using Negative Priming.
We report experiments examining the processing of "extinguished" stimuli in a patient showing visual extinction to double simultaneous stimulation. The experiments used a matching paradigm, designed so that extinguished stimuli cannot benefit from priming from non-extinguished stimuli presented simultaneously. The task involved matching for physical identity central targets in prime and probe displays, flanked by distractors. On "different" trials, distractors in primes could re-appear as targets in probe displays (the ignored repetition condition). Experiments 1 and 3 used normal subjects and established negative priming in the ignored repetition condition. Negative priming occurred both when stimuli in the prime and the probe displays were the same case and when they differed in case. Experiment 2 used a patient manifesting left-field neglect. Like control subjects, he showed negative priming from right-field distractors. In contrast, however, he showed positive priming from left-field distractors. Positive priming also occurred when distractors and targets differed in case (Experim ent 2b). Experiment 4 showed that the patient showed marked left-field extinction under conditions equivalent to those used in the matching task. The data indicate both that "extinguished" stimuli can be processed to activate internal representations and that inhibitory processes may not be applied unless conscious attention is involved.


Atrial Arrhythmias in a Patient Presenting With Coronavirus Disease-2019 (COVID-19) Infection.
The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that has significant potential cardiovascular implications for patients. These include myocarditis, acute coronary syndromes, cardiac arrhythmias, cardiomyopathies with heart failure and cardiogenic shock, and venous thromboembolic events. We describe a Caribbean-Black gentleman with COVID-19 infection presenting with atrial arrhythmias, namely, atrial flutter and atrial fibrillation, which resolved with rate and rhythm control strategies, and supportive care.


Smaller Feedback-Related Negativity (FRN) Reflects the Risky Decision-Making Deficits of Methamphetamine Dependent Individuals.
Methamphetamine (MA) chronic users show risky decision-making deficits. However, the neural mechanisms underlying these deficits remain unclear. A case-control study was conducted to understand how MA users and healthy controls differ in electrophysiological responses associated with series decision-making. Electroencephalography of 31 MA users and 27 healthy controls was recorded when they performed the Balloon Analogue Risk Task involving risky decision-making with uncertain gain or loss. Feedback-related negativity (FRN) was measured and their association with their risky decision-making and impulsivity were examined. Compared to healthy controls, MA users showed smaller peak FRN amplitudes in fronto-central electrodes (F (1, 56) =4.559, p=0.037), and the attenuated peak FRN amplitudes correlated with more risk-taking behavior (r=0.48, p=0.012). Besides, MA users exhibited later FRN (F (1, 56) = 7.561, p=0.008) and earlier P300 (F (1, 56) = 3.582, p = 0.041) compared to healthy controls in fronto-central electrodes, which were correlated with higher score of impulsivity. These findings provided further evidence that MA users showed insensitivity to negative feedback in risky decision-making. FRN might be a promising biomarker of dependence.


Patients who stalk doctors: their motives and management.
The prevalence of stalking is increasing and healthcare professionals are overrepresented among stalking victims. The most common motivations for stalking are patients' developing a romantic attachment, due to delusional beliefs (as in erotomania) or misplaced expectations (often by socially inept patients), and patients' developing a resentment for some supposed injury. Strategies to prevent victimisation and minimise the impact of stalking include: taking care to preserve privacy and security, making clear to patients that the relationship will always be professional and what the boundaries are, informing colleagues and other relevant parties, transferring the patient's care to another doctor, and considering legal action.


Tight clustering and hemizygosity of apomixis-linked molecular markers in Pennisetum squamulatum implies genetic control of apospory by a divergent locus that may have no allelic form in sexual genotypes.
Apomixis is a naturally occurring mode of reproduction that results in embryo formation without the involvement of meiosis or fertilization of the egg. Seed-derived progeny of an apomictic plant are genetically identical to the maternal parent. We are studying a form of apomixis called apospory that occurs in the genus Pennisetum, a taxon in the grass family. A cultivated member of this genus, pearl millet (Pennisetum glaucum), reproduces sexually. A wild relative of pearl millet, Pennisetum squamulatum, that is an obligate aposporous species, is cross-compatible with pearl millet when used as a pollen donor in the interspecific cross. We present herein the genetic mapping of 13 molecular markers in an interspecific hybrid population of 397 individuals that segregates for apomixis and sexuality. Surprisingly, 12 of the 13 markers strictly cosegregated with aposporous embryo sac development, clearly defining a contiguous apospory-specific genomic region in which no genetic recombination was detected. Lack of or suppression of recombination may be coincidentally associated with the chromosomal context of the apomixis locus or it may be a consequence of its evolution that is essential for preservation of gene function as has been previously shown in studies of complex loci in both plant and animal species.


Muscle fiber and motor unit behavior in the longest human skeletal muscle.
The sartorius muscle is the longest muscle in the human body. It is strap-like, up to 600 mm in length, and contains five to seven neurovascular compartments, each with a neuromuscular endplate zone. Some of its fibers terminate intrafascicularly, whereas others may run the full length of the muscle. To assess the location and timing of activation within motor units of this long muscle, we recorded electromyographic potentials from multiple intramuscular electrodes along sartorius muscle during steady voluntary contraction and analyzed their activity with spike-triggered averaging from a needle electrode inserted near the proximal end of the muscle. Approximately 30% of sartorius motor units included muscle fibers that ran the full length of the muscle, conducting action potentials at 3.9 +/- 0.1 m/s. Most motor units were innervated within a single muscle endplate zone that was not necessarily near the midpoint of the fiber. As a consequence, action potentials reached the distal end of a unit as late as 100 ms after initiation at an endplate zone. Thus, contractile activity is not synchronized along the length of single sartorius fibers. We postulate that lateral transmission of force from fiber to endomysium and a wide distribution of motor unit endplates along the muscle are critical for the efficient transmission of force from sarcomere to tendon and for the prevention of muscle injury caused by overextension of inactive regions of muscle fibers.


Cellular toxicity of fecal water depends on diet.
To determine whether concentrations of potentially toxic lipids in the aqueous phase of human stool are responsive to changes in dietary fat, calcium, and fiber, 20 male volunteers were placed on a high-fat, low-calcium, low-fiber or a low-fat, high-calcium, high-fiber diet for 4 days. To assess toxicity of the fecal fractions, we examined the ability of fecal supernatants to lyse human erythrocytes. Bile acid concentrations in fecal water from the low-fat group were reduced significantly from 180 +/- 60 microM to 100 +/- 70 microM; in the high-fat group, increased from 190 +/- 60 microM to 250 +/- 100 microM. Erythrocyte lysis was 76% for the high-fat group, 37% for the low-fat group. There was a significant weak correlation between aqueous bile acid concentration and cell lysis. Results suggest that diet can influence concentrations of detergents in the aqueous phase of human stool and the potential toxicity of this fraction to cell membranes.


The role of Na+ and Ca2+ ions on the action of pancreatic lipase studied with the help of immobilisation techniques.
The role of Na+ and Ca2+ as well as the influence of other metal ions on the lipase action were studied with the aid of immobilisation techniques. By this method it is possible to distinguish between the action of these ions on the lipase molecule itself and their action on the substrate or product. It could be shown that both alkali and alkali earth metal ions, especially Na+, Ca2+ and Mg2+ stabilize active states of the enzyme which were detected by immobilization to controlled pore glass beads. Though Na+ as well as Ca2+ and Mg2+ stabilize the enzyme significantly, they differ in their efficacy. Reasons for this are discussed and the data compared to the findings of other authors who performed their studies with the native enzyme.


Efficient GFP-labeling and analysis of spermatogenic cells using the IRG transgene and flow cytometry.
Spermatogenesis is a highly ordered developmental program that produces haploid male germ cells. The study of male germ cell development in the mouse has provided unique perspectives into the molecular mechanisms that control cell development and differentiation in mammals, including tissue-specific gene regulatory programs. An intrinsic challenge in spermatogenesis research is the heterogeneity of germ and somatic cell types present in the testis. Techniques to separate and isolate distinct mouse spermatogenic cell types have great potential to shed light on molecular mechanisms controlling mammalian cell development, while also providing new insights into cellular events important for human reproductive health. Here, we detail a versatile strategy that combines Cre-lox technology to fluorescently label germ cells, with flow cytometry to discriminate and isolate germ cells in different stages of development for cellular and molecular analyses.


Synthesis, structures, and properties of two three-dimensional metal-organic frameworks, based on concurrent ligand extension.
A tritopic carboxylate ligand, tris(4'-carboxybiphenyl)amine (L-H(3)), has been synthesized and applied in the construction of microporous metal-organic frameworks (MOFs). Two novel metal-organic frameworks (MOFs), {[Zn(2)(L)(OH)]·2DMF·H(2)O}(∞) (1) and {[Cu(L-H)(DMA)]·DMA·2H(2)O}(∞) (2), have been constructed out of L-H(3), Zn(2+), and Cu(2+), respectively. 1 has a 2-fold interpenetrating three-dimensional framework formed by L connectors and the [Zn(2)(CO(2))(3)] secondary building units (SBUs). As for 1, it is worth pointing out that one μ(2)-OH group links two Zn atoms between two neighboring SBUs to produce interesting Zn-O-Zn zigzag chains in the structure. 2 has a two-dimensional grid sheet formed by L-H connectors and the typical paddle-wheel [Cu(2)(CO(2))(4)] SBUs. Two-dimensional (2D) sheets nest with each other, which finally forms a three-dimensional (3D) nested framework. Two MOFs are characterized by infrared (IR) spectroscopy, thermogravimetry, single-crystal and elemental analyses, and powder X-ray diffraction methods. Framework 1' exhibits high permanent porosity (Langmuir surface area = 848 m(2)/g), high thermal stability (up to 450 °C), highly active properties for Friedel-Crafts alkylation reaction, as well as the potential application for the CO(2) gas storage and luminescent material. The catalytic results reveal that 2' is indeed an efficient heterogeneous catalyst for olefin epoxidation reactions.


Improving Spatial Resolution of Multispectral Rock Outcrop Images Using RGB Data and Artificial Neural Networks.
Spectral information provided by multispectral and hyperspectral sensors has a great impact on remote sensing studies, easing the identification of carbonate outcrops that contribute to a better understanding of petroleum reservoirs. Sensors aboard satellites like Landsat series, which have data freely available usually lack the spatial resolution that suborbital sensors have. Many techniques have been developed to improve spatial resolution through data fusion. However, most of them have serious limitations regarding application and scale. Recently Super-Resolution (SR) convolution neural networks have been tested with encouraging results. However, they require large datasets, more time and computational power for training. To overcome these limitations, this work aims to increase the spatial resolution of multispectral bands from the Landsat satellite database using a modified artificial neural network that uses pixel kernels of a single spatial high-resolution RGB image from Google Earth as input. The methodology was validated with a common dataset of indoor images as well as a specific area of Landsat 8. Different downsized scale inputs were used for training where the validation used the ground truth of the original size images, obtaining comparable results to the recent works. With the method validated, we generated high spatial resolution spectral bands based on RGB images from Google Earth on a carbonated outcrop area, which were then properly classified according to the soil spectral responses making use of the advantage of a higher spatial resolution dataset.


[New aspects on the etiology and pathogenesis of arteriosclerosis from the pathologic viewpoint].
Three main atherogenic processes are recognised today: hyperlipemia, arterial wall injury and parietal thrombosis. The role of hyperlipemia is supported, among other things, by the following: 1. Experimentally, protracted hyperlipemia can reproduce faithfully the lesions and all complications of advanced human atherosclerosis. 2. Immunohistochemically, plaque lipoproteins are identical with certain blood lipoproteins. 3. The incidence of atherosclerosis in different populations roughly parallels the average blood lipid levels of these populations. 4. Dietary and pharmacological reductions of blood lipid levels in certain populations have reduced the clinical manifestations of atherosclerosis in these populations. Prolonged hyperlipemia generates arterial plaques by causing penetration of blood lipids into the myocytes of the inner arterial wall, immigration of lipid-laden monocytes into the subendothelial space, and increased endothelial permeability for blood lipoproteins and mitogens. All types of arterial wall injury diminish the endothelial barrier and increase endothelial permeability for blood lipoproteins and mitogenic factors. Seven groups of naturally occurring arterial insults are recognised today: hemodynamic turbulence, hypertension, metabolic insults (including hyperlipemia), immune insults, viruses, exogenous chemicals, and obstruction of adventitial lymphatics. These insults usually cause a functional increase of endothelial permeability (when mild) or a loosening of interendothelial junctions (when intense). Parietal thrombosis develops practically only in atherosclerotic-almost never in normal-arteries. It is most frequently initiated by tiny breaks of plaque surfaces, breaks which expose blood to the highly thrombogenic collagen and lipid masses that abound in the atherosclerotic--but are absent from the normal arterial wall. parietal thrombi are overgrown by endothelium, turned into fibrous tissue and incorporated into the underlying plaques, whose thickness they can thus greatly increase.


The spectrum of Salmonella infection.
Salmonellae have demonstrated an extraordinary capacity to adapt to a wide range of ecologic niches and to the peculiarities of modern society, such as the mass production of food products. The vast majority of infections in the United States are caused by serotypes not specifically adapted to human or animal hosts, whereas the most frequent isolate in developing countries is S. typhi, which is highly adapted to human hosts. The number of isolates reported in the United States has been increasing steadily since 1975, largely a result of outbreaks associated with the mass production of food products, particularly poultry, which is frequently contaminated. Salmonella infection occurs when ingested organisms bypass gastric defenses, multiply within the intestinal lumen, penetrate the intestinal mucosa, and multiply within macrophages of the reticuloendothelial system. They may then disseminate via the systemic circulation. Several virulence factors have been identified. The wide range of pathologic and clinical manifestations are subdivided into four syndromes, each requiring a distinct diagnostic and therapeutic approach: (1) gastroenteritis, (2) enteric fever, (3) bacteremia with or without metastatic disease, and (4) asymptomatic carriage. Although any serotype can cause any of these syndromes, certain serotypes are associated with specific presentations. Serious complications of bacteremic infection include infections of the aorta, endocardium, bone, and meninges. Salmonella infection is particularly severe in patients who have AIDS, leukemia, lymphoma, immunodeficiency of other causes, inflammatory bowel disease, schistosomiasis, and macrophage dysfunction. Diagnosis is based on culture of the organism from appropriate sites. Several serologic tests have been developed that warrant further evaluation. Chloramphenicol, ampicillin, amoxicillin, and trimethoprimsulfamethoxazole have clearly established efficacy. Experience with third generation cephalosporins and quinolones is preliminary and fragmentary, but results suggest that they may prove to be efficacious in certain clinical circumstances. Antibiotic resistance has become a major problem in certain geographic areas. The three vaccines for S. typhi that are currently in use internationally provide only moderate protection for short periods of time.


Secondary metabolites of endophytic fungi isolated from Huperzia serrata.
The natural product Huperzine A isolated from Huperzia serrata is a targeted inhibitor of acetylcholinesterase that has been approved for clinical use in the treatment of Alzheimer's disease. Given the large demand for natural sources of Huperzine A (Hup. A), efforts have been made to explore whether it is also produced by endophytic fungi from H. serrata and, if so, identify its biosynthetic pathway. These studies have indicated that endophytic fungi from H. serrata represent a huge and largely untapped resource for natural products (including Hup. A) with chemical structures that have been optimized by evolution for biological and ecological relevance. To date, more than three hundred endophytic fungi have been isolated from H. serrata, of which 9 strains can produce Hup. A, whilst more than 20 strains produce other important metabolites, such as polyketones, xanthones, alkaloids, steroids, triterpenoids, furanone derivatives, tremulane sesquitepenes and diterpenoids. In total, 200 secondary metabolites have been characterized in endophytic fungi from H. serrata to date. Functionally, some have cholinesterase-inhibitory or antibacterial activity. This review also considers the different classes of secondary metabolites produced by endophytic fungi, along with their possible applications. We systematically describe the taxonomy, biology, and chemistry of these secondary metabolites. It also summarizes the biosynthetic synthesis of metabolites, including that of Hup. A. The review will aid researchers in obtaining a clearer understanding of this plant-endophyte relationship to better exploit the excellent resources it offers that may be utilized by pharmaceutical industries.


The extended nervous system: affect regulation, somatic and social change processes associated with mindful parenting.
A theoretical model of mindful parenting has the potential to succinctly summarise its various change processes. The primary aim of this study was to investigate some of the change processes associated with mindful parenting, namely, the affect regulation, somatic and social change processes. A secondary aim was to verify whether clinical insights are consistent with the change processes identified in a systematic review of mindful parenting. Interpretative Phenomenological Analysis (IPA) was used to analyse semi-structured interviews with four Australian clinicians delivering Mindful Parenting (MP) programs. The clinicians had extensive personal meditation practice. This qualitative study is part of a mixed methods study, which commenced with a quantitative systematic review. Six higher-order themes identified as change processes included reflective functioning, attachment, cognitive, affective, somatic and social change processes. The anchor is a new theoretical model summarising the change processes associated with mindful parenting. The mother portrayed as the extended nervous system for the infant is a neologism that also has not been previously mentioned in the literature. Given the limitations with the small sample and potential bias with interpretation, the anchor is a starting point to developing a theoretical model of mindful parenting. Future research with larger sample sizes and objective measures is needed to confirm whether the anchor is a reasonable summary of the change processes.


Fabrication of monolithic capillary columns with inner diameter 50-530 μm employing a mixture of pentaerythritol tetraacrylate and polyhedral oligomeric silsesquioxane-methacrylate as crosslinkers.
Highly crosslinked monolithic capillary columns with inner diameters in the range of 50-530 μm were prepared by radical polymerization of pentaerythritol tetraacrylate, polyhedral oligomeric silsesquioxane-methacrylate, and n-octadecyl methacrylate in the presence of methanol, dodecyl alcohol, and polyethylene glycol lauryl ether. Columns were evaluated by inverse size-exclusion chromatography employing a set of polystyrene standards of narrow molecular-size distribution and by scanning electron microscopy. Chromatographic performance under reversed-phase conditions was also evaluated. The combination of two effective crosslinkers as pentaerythritol tetraacrylate and polyhedral oligomeric silsesquioxane-methacrylate in the polymerization mixture allows for the preparation of robust and efficient monolithic capillary columns within a fairly wide range of internal diameters.


BALF metagenomic next-generation sequencing analysis in hematological malignancy patients with suspected pulmonary infection: clinical significance of negative results.
Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) is gradually being used in hematological malignancy (HM) patients with suspected pulmonary infections. However, negative results are common and the clinical value and interpretation of such results in this patient population require further analysis. Retrospective analysis of 112 HM patients with suspected pulmonary infection who underwent BALF mNGS and conventional microbiological tests. The final diagnosis, imaging findings, laboratory results and treatment regimen of 29 mNGS-negative patients were mainly analyzed. A total of 83 mNGS positive and 29 negative patients (15 true-negatives and 14 false-negatives) were included in the study. Compared to false-negative patients, true-negative patients showed more thickening of interlobular septa on imaging (p < 0.05); fewer true-negative patients had acute respiratory symptoms such as coughing or sputum production (p < 0.05) clinically; On the aspect of etiology, drug-related interstitial pneumonia (6/15, 40%) was the most common type of lung lesion in true-negative patients; on the aspect of pathogenesis, false-negative patients mainly missed atypical pathogens such as fungi and tuberculosis (8/14, 57.1%). Regarding treatment, delayed anti-infection treatment occurred after pathogen missing in mNGS false-negative patients, with the longest median time delay observed for anti-tuberculosis therapy (13 days), followed by antifungal therapy (7 days), and antibacterial therapy (1.5 days); the delay in anti-tuberculosis therapy was significantly longer than that in antibacterial therapy (p < 0.05). For HMs patients with imaging showing thickening of interlobular septa and no obvious acute respiratory symptoms, lung lesions are more likely caused by drug treatment or the underlying disease, so caution should be exercised when performing BALF mNGS. If BALF mNGS is negative but infection is still suspected, atypical pathogenic infections should be considered.


Nutritional value and potential chemical food safety hazards of selected Polish sausages as influenced by their traditionality.
Traditional food products have been regaining consumer interest worldwide. The aim of the study was to investigate the differences in nutritional value of traditional and conventional Polish sausages and to determine potential chemical hazards connected with these products. The research material consisted of 5 varieties of registered traditional sausages and 4 varieties of conventional sausages. The nutritional value was identified based on selected indicators: protein, fat, NaCl, total ash, water, Feder's number, Ca, Fe, Mg, K, Zn, Cr, Cu; whereas the chemical food safety - based on: nitrates and nitrites, total and added phosphorus, Cd, Pb. The results of this study show that traditional sausages have higher content of protein, zinc, magnesium and potassium as well as lower concentrations of calcium, water and total ash, plus lower water to protein ratio in comparison to conventional counterparts. Polyphosphates are not used in the production of traditional sausages and the amounts of added nitrites are at low levels.


On the chemistry of ethanol on basic oxides: revising mechanisms and intermediates in the Lebedev and Guerbet reactions.
A common way to convert ethanol into chemicals is by upgrading it over oxide catalysts with basic features; this method makes it possible to obtain important chemicals such as 1-butanol (Guerbet reaction) and 1,3-butadiene (Lebedev reaction). Despite their long history in chemistry, the details of the close inter-relationship of these reactions have yet to be discussed properly. Our present study focuses on reactivity tests, in situ diffuse reflectance infrared Fourier transform spectroscopy, MS analysis, and theoretical modeling. We used MgO as a reference catalyst with pure basic features to explore ethanol conversion from its very early stages. Based on the obtained results, we formulate a new mechanistic theory able to explain not only our results but also most of the scientific literature on Lebedev and Guerbet chemistry. This provides a rational description of the intermediates shared by the two reaction pathways as well as an innovative perspective on the catalyst requirements to direct the reaction pathway toward 1-butanol or butadiene.


Polymeric nanogel formulations of nucleoside analogs.
Nanogels are colloidal microgel carriers that have been recently introduced as a prospective drug delivery system for nucleotide therapeutics. The crosslinked protonated polymer network of nanogels binds oppositely charged drug molecules, encapsulating them into submicron particles with a core-shell structure. The nanogel network also provides a suitable template for chemical engineering, surface modification and vectorisation. This review reveals recent attempts to develop novel drug formulations of nanogels with antiviral and antiproliferative nucleoside analogs in the active form of 5'-triphosphates, discusses structural approaches to the optimisation of nanogel properties, and discusses the development of targeted nanogel drug formulations for systemic administration. Notably, nanogels can improve the CNS penetration of nucleoside analogs that are otherwise restricted from passing across the blood-brain barrier. The latest findings reviewed here demonstrate an efficient intracellular release of nucleoside analogs, encouraging further applications of nanogel carriers for targeted drug delivery.


Performance evaluation of a Loeb-Eiber mass filter at 1 Torr.
The Loeb-Eiber mass filter is best operated at relatively high pressures-such as 1 Torr-where collisional dampening of ions up to the mass filter thermalizes the ions' kinetic energy, which is a requirement for effective filtering. The inter-electrode gaps of ~8 μm require rf amplitudes on the order of 0-5 V p-p at approximately 50 MHz to achieve mass filtering up to m/z 40. Mass filtering between the 25-μm diameter wires, therefore, takes place on time frames less than the collision frequency at ~1 Torr. The low power and high pressure capabilities of the Loeb-Eiber mass filter make it ideally suited for miniaturization, where power and space are a premium. In the present work, a Loeb-Eiber mass filter was constructed using commercial silicon-on-insulator (SOI) microfabrication techniques. Ions transmitting through the chip-based Loeb-Eiber mass filter were characterized in real time using a traditional linear quadrupole mass analyzer in series with the Loeb-Eiber mass filter. The new hybrid instrument has enabled us to verify several important claims regarding the operation of the Loeb-Eiber mass filter: (1) that ions can be effectively filtered at ~1 Torr, (2) that for ions of a fixed mass-to-charge ratio, the ion transmission current decreases linearly with increasing rf amplitude on the Loeb-Eiber mass filter, (3) that the cutoff voltage at which all ions of a particular m/z value are effectively blocked is linearly related to mass-to-charge, and (4) that square waveforms can filter ions more effectively than sinusoidal waveforms for a given peak-to-peak rf amplitude.


Growth hormone and somatostatin gene expression in pituitary adenomas with active acromegaly and minimal plasma growth hormone elevation.
Some patients with active acromegaly have elevated plasma IGF-I concentrations with only minimal elevation of plasma GH. We compared adenomatous GH and SRIH expression in 3 such patients (patients No. 1, 2 and 3; basal plasma GH level less than 4 micrograms/l) and in 3 acromegalic patients with high basal plasma GH level (patients No. 4, 5 and 6; 51.7 +/- 16.1 micrograms/l, mean +/- SEM). By immunocytochemistry, all the tumours proved to be somatotropic adenomas. At the ultrastructural level, signs of low secretory activity were observed in adenomas from patients No. 2 and 3. Perifused adenoma cells of patients No. 1, 2 and 3 released very little GH compared with those of patients No. 4, 5 and 6 (1 +/- 0.37 vs 51.5 +/- 34.1 micrograms x (10(-6) cells) x min-1, p less than 0.001). Adenoma SRIH content was 65.7 and 30.6 pg/mg proteins in patients No. 1 and 2, whereas it was undetectable in the others (patients No. 4, 5 and 6). Northern blot analysis showed that the GH gene was poorly expressed in the adenomas from patients No. 1, 2 and 3 compared with the adenomas from patients No. 4, 5 and 6. SRIH mRNA was detected in all 6 adenomas. However, the signal was more intense in the adenomas from patients No. 1, 2 and 3 than in those from patients No. 4, 5 and 6.(ABSTRACT TRUNCATED AT 250 WORDS)


Minor or occult ankle instability as a cause of anterolateral pain after ankle sprain.
The aim of this study was to determine which intra-articular injuries are associated with chronic anterolateral pain and functional instability after an ankle sprain. From 2008 to 2010, records of all patients who underwent ankle joint arthroscopy with anterolateral pain and functional instability after an ankle sprain were reviewed. A systematic arthroscopic examination of the intra-articular structures of the ankle joint was performed. Location and characteristics of the injuries were identified and recorded. A total of 36 ankle arthroscopic procedures were reviewed. A soft-tissue occupying mass over the lateral recess was present in 18 patients (50%). A partial injury of the anterior talofibular ligament (ATFL) was observed in 24 patients (66.6%). Cartilage abrasion due to the distal fascicle of the anteroinferior tibiofibular ligament coming into contact with the talus was seen in 21 patients (58.3%), but no thickening of the ligament was observed. Injury to the intra-articular posterior structures, including the transverse ligament in 19 patients (52.7%) and the posterior surface of the distal tibia in 21 patients (58.3%), was observed. Intra-articular pathological findings have been observed in patients affected by anterolateral pain after an ankle sprain. Despite no demonstrable abnormal lateral laxity, morphologic ATFL abnormality has been observed on arthroscopic evaluation. An injury of the ATFL is present in patients with chronic anterolateral pain and functional instability after an ankle sprain. A degree of microinstability due to a deficiency of the ATFL could explain the intra-articular pathological findings and the patients' complaints. IV.


Spike-Timing-Dependent Plasticity Mediated by Dopamine and its Role in Parkinson's Disease Pathophysiology.
Parkinson's disease (PD) is a multi-systemic neurodegenerative brain disorder. Motor symptoms of PD are linked to the significant dopamine (DA) loss in substantia nigra pars compacta (SNc) followed by basal ganglia (BG) circuit dysfunction. Increasing experimental and computational evidence indicates that (synaptic) plasticity plays a key role in the emergence of PD-related pathological changes following DA loss. Spike-timing-dependent plasticity (STDP) mediated by DA provides a mechanistic model for synaptic plasticity to modify synaptic connections within the BG according to the neuronal activity. To shed light on how DA-mediated STDP can shape neuronal activity and synaptic connectivity in the PD condition, we reviewed experimental and computational findings addressing the modulatory effect of DA on STDP as well as other plasticity mechanisms and discussed their potential role in PD pathophysiology and related network dynamics and connectivity. In particular, reshaping of STDP profiles together with other plasticity-mediated processes following DA loss may abnormally modify synaptic connections in competing pathways of the BG. The cascade of plasticity-induced maladaptive or compensatory changes can impair the excitation-inhibition balance towards the BG output nuclei, leading to the emergence of pathological activity-connectivity patterns in PD. Pre-clinical, clinical as well as computational studies reviewed here provide an understanding of the impact of synaptic plasticity and other plasticity mechanisms on PD pathophysiology, especially PD-related network activity and connectivity, after DA loss. This review may provide further insights into the abnormal structure-function relationship within the BG contributing to the emergence of pathological states in PD. Specifically, this review is intended to provide detailed information for the development of computational network models for PD, serving as testbeds for the development and optimization of invasive and non-invasive brain stimulation techniques. Computationally derived hypotheses may accelerate the development of therapeutic stimulation techniques and potentially reduce the number of related animal experiments.


A morphological investigation of sexual and lateral dimorphism in the developing metanephric kidney.
Sexual dimorphism is a prominent feature of renal physiology and as a consequence, it differentially affects predisposition to many adult kidney diseases. Furthermore the left and right kidneys differ in terms of their position, size and involvement in congenital malformations of the urogenital tract. We set out to determine whether differences in the program of branching morphogenesis that establishes the basic architecture of the kidney were apparent with respect to either sex or laterality in mouse embryonic kidneys. This was achieved using a combination of optical projection tomography imaging and computational analysis of many spatial metrics describing the branched ureteric tree. We undertook a comprehensive assessment of twelve aspects of ureteric morphology across developmental time and we found no consistent differences between kidneys of different sexes or laterality. These results suggest that dimorphism is established after birth or at a physiological or cellular level that is not reflected in the morphology of the ureteric tree.


Detection of anti-neutrophil cytoplasmic antibodies under actual clinical testing conditions.
Anti-neutrophil cytoplasmic antibodies (ANCA) are a useful diagnostic tool for Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). To maximize diagnostic utility, current guidelines recommend dual testing by standard indirect immunofluorescence (IIF) and target antigen-specific assays. Most published data come from specialized research laboratories, not reflecting the performance of assays under routine clinical conditions. Therefore, we compared the performance of standard IIF, PR3-, and MPO-ANCA-specific direct ELISA, and a PR3-ANCA-specific capture ELISA used alone and in combination under routine clinical conditions. Consecutive serum samples (615) submitted for routine ANCA testing over a 10-month period were assayed. Diagnoses were WG/MPA (n = 86), other autoimmune disease (n = 118), and various others (n = 411). The combination of PR3-ANCA and MPO-ANCA ELISA had the highest sensitivity (72.1%), and C-ANCA determination using IIF, the highest specificity (99.6%). While maintaining maximal diagnostic accuracy, significant labor savings are achieved by screening for WG/MPA by ELISA followed by confirmatory IIF.


The lasso technique for posterior C1-C2 fusion.
Posterior atlantoaxial arthrodesis requires placement of a bone graft in a properly prepared environment that includes decorticated bony surfaces, compressive forces between graft and native bone, and limited motion. To achieve posterior atlantoaxial arthrodesis, various cable-and-graft constructs have been used, all of which require an intact posterior arch of C1. For patients who lack an intact arch owing to congenital, iatrogenic, or traumatic causes, we have devised the "lasso technique," which uses the remnants of the posterior arch of C1 for placement of the graft to achieve fusion isolated to C1-C2 or to be part of an occipitocervical construct. A retrospective record review was conducted of all patients who underwent the lasso technique. Clinical and radiographic history, perioperative course, and time to fusion were recorded. We describe the technique in detail. During the last 13 years, we have used this technique successfully in five female and four male patients. The absent or incompetent posterior arch was a congenital defect in one patient, a result of prior surgical removal in four patients, and caused by fracture associated with prior failed fusion attempts in four other patients. All patients experienced successful fusion after an average of 6.8 months. Securing a bone graft in the absence of an intact C1 lamina is a challenge when a patient presents with atlantoaxial instability. We have devised the lasso technique to secure an interpositional C1-C2 graft using the remnants of the posterior atlantal arch. Although this technique has been required relatively infrequently, we have found it to be valuable and effective in our practice.


Efficacy of AKT Inhibitor ARQ 092 Compared with Sorafenib in a Cirrhotic Rat Model with Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related mortality worldwide. The AKT pathway has been found activated in 50% of HCC cases, making it a promising target. Therefore, we assess efficacy of the allosteric AKT inhibitor ARQ 092 compared with untreated control and standard treatment, sorafenib, in vitro and in vivo ARQ 092 blocked phosphorylation of AKT in vitro and strongly inhibited cell growth with significantly higher potency than sorafenib. Similarly, apoptosis and cell migration were strongly reduced by ARQ 092 in vitro To mimic human advanced HCC, we used a diethylnitrosamine-induced cirrhotic rat model with fully developed HCC. MRI analyses showed that ARQ 092 significantly reduced overall tumor size. Furthermore, number of tumors was decreased by ARQ 092, which was associated with increased apoptosis and decreased proliferation. Tumor contrast enhancement was significantly decreased in the ARQ 092 group. Moreover, on tumor tissue sections, we observed a vascular normalization and a significant decrease in fibrosis in the surrounding liver of animals treated with ARQ 092. Finally, pAKT/AKT levels in ARQ 092-treated tumors were reduced, followed by downregulation of actors of AKT downstream signaling pathway: pmTOR, pPRAS40, pPLCγ1, and pS6K1. In conclusion, we demonstrated that ARQ 092 blocks AKT phosphorylation in vitro and in vivo In the HCC-rat model, ARQ 092 was well tolerated, showed antifibrotic effect, and had stronger antitumor effect than sorafenib. Our results confirm the importance of targeting AKT in HCC. Mol Cancer Ther; 16(10); 2157-65. ©2017 AACR.


Association between a vasopressin receptor AVPR1A promoter region microsatellite and eating behavior measured by a self-report questionnaire (Eating Attitudes Test) in a family-based study of a nonclinical population.
Considerable evidence including twin and family studies suggests that biologic determinants interact with cultural cues in the etiology of anorexia and bulimia nervosa. A gene that makes "biologic sense" in contributing susceptibility to these disorders, and to our knowledge not previously investigated for this phenotype, is the vasopressin receptor (AVPR1A), which we have tested for association with eating pathology. We genotyped 280 families with same-sex siblings for two microsatellites in the promoter region of the AVPR1A gene. Siblings completed the 26-item Eating Attitudes Test (EAT) and the Drive for Thinness (DT) and Body Dissatisfaction (BD) subscales of the Eating Disorders Inventory (EDI). The Quantitative Transmission Disequilibrium Test program (QTDT), which employs flexible and powerful variance-components procedures, was used to test for an association between EAT scores and the two AVPR1A promoter region microsatellites, RS1 and RS3. A significant association (p = .036) was detected between the RS3 microsatellite and EAT scores. The strongest association was between RS3 and the Dieting subscale of the EAT (p = .011). A significant association was also observed between the EDI-DT and the RS3 microsatellit (p = .0450). We demonstrate for the first time an association between a microsatellite polymorphism in the AVPR1A promoter region and scores on the EAT as well as with the EDI-DT. The strongest association was observed between the RS3 microsatellite and the Dieting subscale of the EAT. The relevant phenotype appears to tap severe dietary restriction for weight loss purposes.


[Double teeth].
Double teeth are not really rare, but it is still enigmatic why and how they develop. Based upon the clinical, morphological and anatomical appearance and the number of teeth in mouths with double teeth, the double teeth are labelled as products of 'fusion' and 'clefting', but the criteria to attach such etiological names are lacking. It is assumed that heredity is involved in the development of double teeth. Therefore it is attempted to explain why only one of a homozygotic twin had a double tooth.


[Lumps and bumps. Diagnosis and management of soft-tissue tumors].
Patients with soft-tissue tumours usually consult for a mass at the level of an extremity or the torso. This article aims to help the general practitioner and the general surgeon in the standardized setup of these tumours. The epidemiology, clinical presentation and evaluation as well as the useful exams to be performed, including biopsy, are developped, in order to obtain rational principles for the diagnostic setup and surgical decision-making.


A patient and family data domain collection framework for identifying disparities in pediatrics: results from the pediatric health equity collaborative.
By 2020, the child population is projected to have more racial and ethnic minorities make up the majority of the populations and health care organizations will need to have a system in place that collects accurate and reliable demographic data in order to monitor disparities. The goals of this group were to establish sample practices, approaches and lessons learned with regard to race, ethnicity, language, and other demographic data collection in pediatric care setting. A panel of 16 research and clinical professional experts working in 10 pediatric care delivery systems in the US and Canada convened twice in person for 3-day consensus development meetings and met multiple times via conference calls over a two year period. Current evidence on adult demographic data collection was systematically reviewed and unique aspects of data collection in the pediatric setting were outlined. Human centered design methods were utilized to facilitate theme development, facilitate constructive and innovative discussion, and generate consensus. Group consensus determined six final data collection domains: 1) caregivers, 2) race and ethnicity, 3) language, 4) sexual orientation and gender identity, 5) disability, and 6) social determinants of health. For each domain, the group defined the domain, established a rational for collection, identified the unique challenges for data collection in a pediatric setting, and developed sample practices which are based on the experience of the members as a starting point to allow for customization unique to each health care organization. Several unique challenges in the pediatric setting across all domains include: data collection on caregivers, determining an age at which it is appropriate to collect data from the patient, collecting and updating data at multiple points across the lifespan, the limits of the electronic health record, and determining the purpose of the data collection before implementation. There is no single approach that will work for all organizations when collecting race, ethnicity, language and other social determinants of health data. Each organization will need to tailor their data collection based on the population they serve, the financial resources available, and the capacity of the electronic health record.


Growth inhibition in normal mammalian melanocytes in vitro.
Studies on primary cultures of normal adult melanocytes from the ear skin of a black strain of guinea-pigs are reported. Melanocytes have a low proliferation rate and tend to form cohesive groups on a glass surface. The cells undergo division while maintaining close contacts with each other whereas DNA synthesis is rare in melanocytes with multiple contacts.


Protecting the health of United States military forces in Afghanistan: applying lessons learned since the Gulf War.
Four weeks after the terrorist attacks on the World Trade Center and the Pentagon, US combat troops began bombing missions over Afghanistan in Operation Enduring Freedom. Additional Reserve and National Guard personnel were called to active duty to support the war effort and to ensure security throughout the United States. All of these troops will require health care and assistance during and after this war on terrorism. They will benefit from recent federal legislation that has increased access to health care and from the changes implemented by the Departments of Defense and Veterans Affairs since the Gulf War. An innovative Defense Department "Force Health Protection" strategy places greater emphasis on helping service members and families stay healthy and fit and on preventing injury and illness. The two agencies also have developed new post-deployment clinical practice guidelines, established deployment research centers, and made further improvements in preventive medicine, health surveillance, and risk communication and are thus better prepared for this newest generation of war veterans.


Coordinate regulation of drug metabolism by xenobiotic nuclear receptors: UGTs acting together with CYPs and glucuronide transporters.
Xenobiotic nuclear receptors (PXR, CAR, and the Ah receptor) coordinately induce genes involved in all phases of xenobiotic metabolism including oxidative metabolism, conjugation, and transport. The comment--dedicated to honor the memory of Herbert Remmer, mentor of the author K. W. B.--discusses mechanistic, functional, and evolutionary aspects of xenobiotic nuclear receptors which induce UGTs together with CYPs and glucuronide transporters in human and rodent liver and intestine. Recent findings on regulation of CYPs, UGTs, and transporters suggest that while nuclear receptor signaling induces different CYPs, regulation may converge on single UGTs and transporters. Functional consequences of co-regulation are discussed using examples from the metabolism of xeno- and endobiotics (drugs, bilirubin, bile salts, steroid hormones, and carcinogens). Animal-plant interactions may have been a major driving force in the evolutionary divergence of CYPs and UGTs in mammals and insects as well as in their regulation by nuclear receptors. In addition, regulation by nuclear receptors was probably shaped by the need for homeostatic control of endobiotic signals in the evolution of multicellular organisms.


High-power liquid-lithium jet target for neutron production.
A compact liquid-lithium target (LiLiT) was built and tested with a high-power electron gun at the Soreq Nuclear Research Center. The lithium target, to be bombarded by the high-intensity proton beam of the Soreq Applied Research Accelerator Facility (SARAF), will constitute an intense source of neutrons produced by the (7)Li(p,n)(7)Be reaction for nuclear astrophysics research and as a pilot setup for accelerator-based Boron Neutron Capture Therapy. The liquid-lithium jet target acts both as neutron-producing target and beam dump by removing the beam thermal power (>5 kW, >1 MW/cm(3)) with fast transport. The target was designed based on a thermal model, accompanied by a detailed calculation of the (7)Li(p,n) neutron yield, energy distribution, and angular distribution. Liquid lithium is circulated through the target loop at ~200 °C and generates a stable 1.5 mm-thick film flowing at a velocity up to 7 m/s onto a concave supporting wall. Electron beam irradiation demonstrated that the liquid-lithium target can dissipate electron power areal densities of >4 kW/cm(2) and volume power density of ~2 MW/cm(3) at a lithium flow of ~4 m/s while maintaining stable temperature and vacuum conditions. The LiLiT setup is presently in online commissioning stage for high-intensity proton beam irradiation (1.91-2.5 MeV, 1-2 mA) at SARAF.


Novel Insights Into Effects of Cortisol and Glucagon on Nocturnal Glucose Production in Type 2 Diabetes.
The effect of physiological changes in night-time cortisol and glucagon on endogenous glucose production (EGP) and nocturnal glycemia are unknown. To determine the effects of changes in cortisol and glucagon on EGP during the night. Two overnight protocols were conducted. In Protocol 1, endogenous cortisol was blocked with metyrapone and hydrocortisone infused either at constant (constant) or increasing (variable) rates to mimic basal or physiological nocturnal cortisol concentrations. In Protocol 2, endogenous glucagon was blocked with somatostatin and exogenous glucagon was infused at either basal or elevated rates to mimic nocturnal glucagon concentrations observed in nondiabetic (ND) and type 2 diabetes (T2D) individuals. EGP was measured using [3-3H] glucose and gluconeogenesis estimated with 2H2O in all studies. Mayo Clinic Clinical Research Trials Unit, Rochester, MN, US. In Protocol 1, 34 subjects (17 ND and 17 T2D) and in Protocol 2, 39 subjects (21 ND and 18 T2D) were studied. Endogenous glucose production. EGP, gluconeogenesis, and glycogenolysis were higher with variable than with constant cortisol at 7 am in T2D subjects. In contrast, nocturnal EGP did not differ in ND subjects between variable and constant cortisol. While elevated glucagon increased EGP, glycogenolysis, and gluconeogenesis in ND, the data in T2D subjects indicated that EGP and gluconeogenesis but not glycogenolysis were higher during the early part of the night. Nocturnal hyperglucagonemia, but not physiological rise in cortisol, contributes to nocturnal hyperglycemia in T2D due to increased gluconeogenesis.


A paediatric trauma study of scooter injuries.
To investigate the incidence and describe the nature of non-motorized scooter related injuries in children presenting to the ED. Paediatric ED of a metropolitan tertiary referral hospital. A prospective observational study of patients aged under 19 years presenting with injuries sustained while using a non-motorized scooter. Clinicians recorded the data in the patient record. type of injury sustained; period of experience on the scooter; the use of protective gear; the presence of adult supervision; the place of accident; and the patient outcome. Sixty-two eligible patients were recruited over an 18 month period. The incidence of scooter- related injuries was 1.3% of all paediatric trauma presentations. There was a fall in scooter injury presentations over the study period; however, this was not statistically significant. The most common injury sustained using a scooter was an upper limb fracture (41.9%). Closed head injury comprised 8.1% of all scooter related injuries. The majority of patients were not wearing protective gear and were unsupervised at the time of their accident. Most patients (79%) were managed in the ED and discharged. There has been no significant change in scooter injury presentations over the two summer periods of 2000 and 2001. Children presenting to the ED with a scooter related injury tend to be primary school aged, which may have implications on scooter design, age recommendations and safety guidelines.


Binding properties of human anti-DNA antibodies to cloned human DNA fragments.
The DNA-anti-DNA antibody immune complexes were isolated from plasma of systemic lupus erythematosus (SLE) patients and DNA fragments separated from immune complexes were subjected to molecular cloning. The resulting recombinant DNA clones showed a molecular size of 37-79 base pairs, a high guanine and cytosine content, high frequencies of CpG dinucleotides, and palindromic sequences, and also clusters of G + C- and A + T-rich segments. These clones hybridized randomly to total human DNA. The reactivity of dsDNA antibodies, both monoclonal and polyclonal, from SLE was examined with a cloned SLE antigen DNA. A competitive inhibition assay showed that human monoclonal antibodies had at least one magnitude higher affinity to the cloned DNA than to the native DNA fragments. In order to characterize the factors that were recognized by antibodies, human G + C-rich and also A + T-rich 100 bp DNA fragments were cloned, and their base sequences determined. The antibody showed a higher affinity to the G + C-rich DNA fragment (71% G + C) than to the A + T-rich DNA fragment (46% G + C). When cytosines in CpG doublets in G + C-rich fragments were methylated (mCpG), the reactivity increased up to 100-fold. The native anti-DNA antibodies from SLE patients also showed preferential binding to G + C-rich fragments. These observations suggested that human anti-dsDNA antibodies may recognize some unique structures around the G + C regions or G + C clusters of DNA.


IgG4-related disease: an analysis of the clinicopathological spectrum: UK centre experience.
To retrospectively evaluate the characteristic clinicopathological spectrum in patients with suspicion of IgG4-related disease (IgG4RD). Winpath histology database from January 2011 to April 2018 identified all suspected IgG4RD cases wherein IgG4 immunohistochemistry was performed. The histology slides were reviewed to categorise cases into Boston criteria groups-highly suggestive of IgG4RD, probable IgG4RD and insufficient evidence. Information regarding clinical data, treatment received, follow-up and serum IgG4 levels was obtained from medical records and AllScripts Patient Administration System (APAS) clinical database. The study included 204 patients and the most common sites of biopsy/resection were pancreas and duodenum. The most common clinical presentation was fibroinflammatory lesion or mass/lump. On histology, 54/204 (26.47%) cases showed typical storiform fibrosis, 65/204 (32.64%) had >10 IgG4+ plasma cells per high power field and only one case showed thrombophlebitis (0.49%). There were 14/204 (6.78%) cases categorised as highly suggestive of IgG4RD; 8 of these showed high serum IgG4 levels and were managed clinically as true IgG4RD. Histological diagnosis of IgG4RD remains challenging, as not all characteristic features are always present especially in small biopsies. Due to the novelty of its experience, fear of over diagnosis in the context of malignancy and features overlapping with diseases of similar clinical scenario, diagnosis of IgG4RD has become more puzzling. Further multicentre clinical trials/studies are advisable.


Cardiovascular risks associated with calcium supplementation in patients with osteoporosis: a nationwide cohort study.
This study aimed to evaluate the real effects of calcium supplementation on cardiovascular outcomes within a population-based cohort. From a nationwide health screening database in South Korea, a total of 11 297 patients with osteoporosis who had taken calcium supplementation with or without vitamin D for at least 90 days [total calcium group; calcium supplementation only (CaO), n = 567; calcium supplementation in combination with vitamin D (CaD), n = 10 730] were matched at a 1:1 ratio to patients who had not taken calcium supplements (control group) by using propensity scores. The overall mean age was 59.9 ± 8.8 years and the percentage of women was 87.9% in our study population. Over a median follow-up of 54 months, the incidence rate of composite cardiovascular diseases (CVDs) per 1000 person-years was not different between the groups: 9.73 in the total calcium group and 8.97 in the control group [adjusted hazard ratio (HR): 1.12; 95% confidence interval (CI): 0.99-1.28; P = 0.08]. However, calcium supplementation without vitamin D was associated with an increased risk of composite CVD (HR: 1.54; 95% CI: 1.17-2.04; P < 0.01), especially non-fatal myocardial infarction (HR: 1.89; 95% CI: 1.23-2.91; P < 0.01), compared with no calcium supplementation. Our population-based study supported that taking calcium supplementation combined with vitamin D did not appear to be harmful to cardiovascular health, but reminded that calcium supplementation without vitamin D should be used carefully even in populations with low dietary calcium intake.


Using Feature Engineering and Principal Component Analysis for Monitoring Spindle Speed Change Based on Kullback-Leibler Divergence with a Gaussian Mixture Model.
Machining is a crucial constituent of the manufacturing industry, which has begun to transition from precision machinery to smart machinery. Particularly, the introduction of artificial intelligence into computer numerically controlled (CNC) machine tools will enable machine tools to self-diagnose during operation, improving the quality of finished products. In this study, feature engineering and principal component analysis were combined with the online and real-time Gaussian mixture model (GMM) based on the Kullback-Leibler divergence's measure to achieve the real-time monitoring of changes in manufacturing parameters. Based on the attached accelerometer device's vibration signals and current sensing of the spindle, the developed GMM unsupervised learning was successfully used to diagnose the spindle speed changes of a CNC machine tool during milling. The F1-scores with improved experimental results for X, Y, and Z axes were 0.95, 0.88, and 0.93, respectively. The established FE-PCA-GMM/KLD method can be applied to issue warnings when it predicts a change in the manufacturing process parameter. A smart sensing device for diagnosing the machining status can be fabricated for implementation. The effectiveness of the developed method for determining the manufacturing parameter changes was successfully verified by experiments.


Relationship between urine lipid peroxidation, anthropometric parameters and parameters associated with goitre formation in school-age children.
Oxidative stress has been implicated in the normal ageing process and the pathogenesis of several diseases, including goitre. The aim of the study was to evaluate the relationship between urine lipid peroxidation (LPO) and anthropometric parameters as well as the parameters associated with goitre formation in children. The subjects included 172 healthy children (93 girls and 79 boys) aged 8-15, divided into 4 age groups - group I (8-9 years), group II (10-11 years), group III (12-13 years) and group IV (14-15 years) - and into 2 groups based on the BSA: the BSA-1 group (≤ 0.55 m2) and the BSA-2 group (> 0.55 m2). The value of LPO was the highest in group I but the difference between the groups was not statistically significant (p = 0.074). In the BSA-1 group, the LPO was higher than in the BSA-2 group (12.75 ±6.90 nmol/ml and 10.79 ±4.86 nmol/ml, respectively; p = 0.023). We found a weak, negative linear correlation between LPO and age (r = -0.216; p < 0.005), body mass (r = -0.153; p < 0.05), height (r = -0.152; p < 0.05) and BSA (r = -0.151; p < 0.05). Anthropometric parameters of school-age children independently of age are negatively associated with oxidative damage to membrane lipids, whereas factors promoting goitrogenesis do not contribute to this process.


Structural and Electronic Flexibility in Hydrides of Zintl Phases with Tetrel-Hydrogen and Tetrel-Tetrel Bonds.
The hydrogenation of Zintl phases enables the formation of new structural entities with main-group-element-hydrogen bonds in the solid state. The hydrogenation of SrSi, BaSi, and BaGe yields the hydrides SrSiH5/3-x, BaSiH5/3-x and BaGeH5/3-x . The crystal structures show a sixfold superstructure compared to the parent Zintl phase and were solved by a combination of X-ray, neutron, and electron diffraction and the aid of DFT calculations. Layers of connected HSr4 (HBa4 ) tetrahedra containing hydride ions alternate with layers of infinite single- and double-chain polyanions, in which hydrogen atoms are covalently bound to silicon and germanium. The idealized formulae AeTtH5/3 (Ae=alkaline earth, Tt=tetrel) can be rationalized with the Zintl-Klemm concept according to (Ae2+ )3 (TtH- )(Tt2 H2- )(H- )3 , where all Tt atoms are three-binding. The non-stoichiometry (SrSiH5/3-x , x=0.17(2); BaGeH5/3-x , x=0.10(3)) can be explained by additional π-bonding of the Tt chains.


The effect of routine radiological reporting of thyroid incidentalomas on rates of thyroid needle biopsy, thyroid surgery and detection of thyroid malignancy.
This study looked at the effect of a changing radiology reporting policy to routinely review the thyroid gland where visible and report on any thyroid lesion, recommending further investigation as appropriate. Incidentaloma is a term used to describe a lesion found on imaging unrelated to the clinical issue under investigation. There is variability in the radiological reporting of thyroid incidentalomas and conflicting recommendations as to how these lesions should be managed. Data were collected retrospectively during a two-year period, including 12 months before and 12 months after the change in reporting policy and categorized according to whether the lesion under investigation was a thyroid incidentaloma or a symptomatic thyroid lesion. All patients undergoing ultrasound-guided fine-needle aspiration cytology or core biopsy were included. The effects of the change in policy were analysed including rates of needle biopsy, rates of malignancy and subsequent surgical intervention. There was a 122% increase in thyroid incidentalomas undergoing needle biopsy, the majority of these were detected on computed tomography. The number of malignancies increased from 1 to 4 from year 1 to year 2. All patients were >35 years old. One patient had a positron emission tomography (PET)-detected cancer, two of four of the non-PET-detected malignancies were <1.5 cm. This study posits that routine radiological reporting of thyroid incidentalomas, with further investigation when clinically appropriate, is warranted. The results suggest that lesion size and CT characteristics are not reliable criteria to triage patients for investigation/biopsy.


Historical and clinical perspectives on de qi: exposing limitations in the scientific study of de qi.
De qi is a concept most often associated with patient experiences during needling in acupuncture treatment. A review of the early historical literature on acupuncture shows that texts tended to describe de qi and its associated concept, qi zhi more in terms of practitioner-based phenomena and that this is something more in the realm of the experienced practitioner (i.e., it is skill based). Many modern authors in Asia and the West also describe the importance of practitioner-based experiences in the de qi of acupuncture, further implying that this may lie at the heart of the treatment effects of acupuncture. A review of scientific studies on de qi shows that qualitative studies have focused almost exclusively on patient-based aspects of de qi while quantitative studies have focused exclusively on them. There thus exists a gap in current research on the phenomenon of de qi that possibly reveals weakness in the wider study of acupuncture. It is important that precise qualitative studies of the practitioner-based aspects of de qi begin soon and as they become better understood, quantitative research also is initiated. This research will not only better inform clinical trials and physiologic research of acupuncture in general but could contribute significantly to rethinking of how to train practitioners.


[Birth asphyxia, neonatal risk factors for hypoxic ischemic encephalopathy].
Neonates suffering from severe birth asphyxia may develop hypoxic ischemic encephalopathy (HIE), some of which develop permanent neurological damage. As the incidence of asphyxia and HIE in Iceland is unknown, this study was conducted. Furthermore, we evaluated the association between some neonatal risk factors and the development of HIE. All term infants born at LSH from 1997-2001 with birth asphyxia, defined as 5 minute Apgar score or=<6, were included in the study. Clinical information, length and weight, Apgar scores at 1, 5 and 10 minutes normoblasts count, initial pH and hemoglobin levels were retrospectively collected. The incidence of HIE after birth asphyxia was 1.4/1000. The infants who developed HIE had significantly lower birth weight and Apgar scores at one, five and ten minutes. They also had lower umbilical artery pH, had more base deficit and lower serum bicarbonate concentrations than the infants who did not develop HIE. The incidence of HIE was low compared to other studies. Birth asphyxia resulting in HIE is associated with lower birth weight, Apgar scores, pH and neonatal hemoglobin levels at birth. We conclude that neonates with low hemoglobin level are at increased risk for developing HIE and that low pH and Apgar scores may predict worse outcomes after birth asphyxia.


Brain lesions associated with acute toxic hepatopathy in cattle.
Samples of the liver, telencephalon, brainstem, and cerebellum were obtained from 22 bovids suffering from spontaneous or experimental acute toxic liver disease. Perreyia flavipes larvae, and leaves of Cestrum corymbosum, Cestrum intermedium, Dodonaea viscosa, Trema micrantha, and Xanthium cavanillesii were the causal agents in the disorders studied. Hematoxylin and eosin and periodic acid-Schiff staining, as well as anti-S100 protein (anti-S100), anti-glial fibrillary acidic protein (anti-GFAP), and anti-vimentin immunostaining were used to evaluate the brain sections. Astrocytic changes were observed in all samples and were characterized by swollen vesicular nuclei in gray (Alzheimer type II astrocytes) and white matter; and by abundant eosinophilic or vacuolated cytoplasm with pyknotic nuclei in the white matter. These changes were evidenced by anti-S100 and anti-GFAP immunostaining. Our study demonstrates major changes in astrocytes of cattle that died with neurologic clinical signs as the result of acute toxic liver disease.


Surgery for tricuspid regurgitation late after mitral valve replacement.
Tricuspid valve insufficiency may contribute to a poor hemodynamic result after mitral valve replacement. To determine the role of surgical treatment, we have reviewed the records of 32 adult patients who underwent tricuspid valve repair or replacement 4 months to 14 years after mitral valve replacement. Mild tricuspid valve insufficiency at the time of mitral valve replacement was present in 21 patients (66%); 26 patients (81%) had New York Heart Association class IV disability. Tricuspid annuloplasty was performed in 16 patients, and the remainder received various prosthetic valves. Concomitant repair of mitral valve periprosthetic leak and/or replacement of the aortic valve was necessary in 18 patients (53%). Hospital mortality was 25%, and all early deaths were related to low cardiac output. Among hospital survivors there have been 14 late deaths for 3 and 5 year actuarial survival rates of 65% and 44%. Twelve of the 14 patients who died late and one of 10 patients who were alive at the end of the follow-up period had little or no functional improvement after tricuspid valve repair or replacement. The high early and late mortality and poor functional outcome for patients undergoing tricuspid valve surgery late after mitral valve replacement contrast with our good overall results in reoperation for prosthetic heart valves. It appears that serious tricuspid valve insufficiency after mitral valve replacement frequently signals right ventricular failure and dilatation; restoring valve competence is palliative. This experience encourages us to continue our policy of liberal indications for tricuspid valve annuloplasty at initial mitral valve replacement.


KEGG mapping tools for uncovering hidden features in biological data.
In contrast to artificial intelligence and machine learning approaches, KEGG (https://www.kegg.jp) has relied on human intelligence to develop "models" of biological systems, especially in the form of KEGG pathway maps that are manually created by capturing knowledge from published literature. The KEGG models can then be used in biological big data analysis, for example, for uncovering systemic functions of an organism hidden in its genome sequence through the simple procedure of KEGG mapping. Here we present an updated version of KEGG Mapper, a suite of KEGG mapping tools reported previously (Kanehisa and Sato, Protein Sci 2020; 29:28-35), together with the new versions of the KEGG pathway map viewer and the BRITE hierarchy viewer. Significant enhancements have been made for BRITE mapping, where the mapping result can be examined by manipulation of hierarchical trees, such as pruning and zooming. The tree manipulation feature has also been implemented in the taxonomy mapping tool for linking KO (KEGG Orthology) groups and modules to phenotypes.


Spinocerebellar ataxia type 6 and episodic ataxia type 2: differences and similarities between two allelic disorders.
Spinocerebellar ataxia type 6 (SCA6) is one of three allelic disorders caused by mutations of CACNA1A gene, coding for the pore-forming subunit of calcium channel type P/Q. SCA6 is associated with small expansions of a CAG repeat at the 3' end of the gene, while point mutations are responsible for its two allelic disorders (Episodic Ataxia type 2 and Familial Hemiplegic Migraine). Genetic, clinical, pathological and pathophysiological data of SCA6 patients are reviewed and compared to those of other SCAs with expanded CAG repeats as well as to those of its allelic channelopathies, with particular reference to Episodic Ataxia type 2. Overall SCA6 appears to share features with both types of disorders, and the question as to whether it belongs to polyglutamine disorders or to channelopathies remains unanswered at present.


Jahn-Teller Effect on Framework Flexibility of Hybrid Organic-Inorganic Perovskites.
Here we study the Jahn-Teller (JT) effect on framework flexibility of two analogous hybrid organic-inorganic perovskites, [C(NH2)3][Zn(HCOO)3] (1-Zn) and [C(NH2)3][Cu(HCOO)3] (2-Cu). Single-crystal nanoindentation measurements show that the elastic moduli and hardnesses of 1-Zn are up to ∼52.0% and ∼25.0% greater than those of the JT active 2-Cu. Temperature-dependent X-ray diffraction measurements indicate that the thermal expansion along the b-axis is switched from negative to positive by replacing Zn2+ with Cu2+ on the B-site. These stark distinctions in framework flexibility are primarily attributed to the ∼10.0% elongation of Cu-O bonds induced by the JT effect and associated alterations in octahedral tilting and hydrogen-bonding. Our results demonstrate the prominence of the JT effect in the emerging hybrid perovskites and highlight the possibilities of tuning materials' properties using orbital order.


Evaluation of the 2023 Kahramanmaras earthquake from the perspective of Plastic Surgery Department: A single-center experience.
The aim of this study was to evaluate the treatment management and demographic data of earthquake victims admitted to Plastic Surgery Department of our center after the 2023 Kahramanmaras earthquake. Between February 6th, 2023 and February 15th, 2023, a total of 120 patients (65 males, 55 females; mean age: 36.3±17.3 years; range, 85 to 88 years) who were consulted to the Plastic Surgery Department of our center were included. Demographic data of the patients, time to admission to the emergency room, removal time under the rubble, type of injury, emergency operation requirement, fasciotomy requirement, hyperbaric oxygen therapy administration, and length of stay in the intensive care unit were evaluated. After the first intervention, patients with compartment syndrome underwent emergency fasciotomy immediately. Perioperative laboratory values of the patients were followed closely to prevent the development of crush syndrome. Due to stay under the rubble, upper extremity soft tissue injury was seen in 46.2% of the patients. The pelvic and abdominal region were the least affected soft tissues in 1.7% patients. Fasciotomy was performed in 75 patients who stayed under the rubble. Hyperbaric oxygen therapy was applied to 21 of 75 patients who underwent fasciotomy. Amputation was performed in four patients, three of which were in the upper extremity and one in the lower extremity, during follow-up after fasciotomy. A total of 10.83% of the patients were treated conservatively and 11.67% of them were reconstructed with free flaps. Totally 7.5% of the patients who stayed under the rubble were hospitalized in our clinic for maxillofacial injuries. A total of 66.6% of these patients were treated surgically, while 33.3% of them were further treated conservatively. Proper triage, proper fasciotomy, and appropriate surgical interventions reduce the amputation rate, yielding clinically satisfactory results.


Mesenchymal stem cells in mammary adipose tissue stimulate progression of breast cancer resembling the basal-type.
Data are accumulating to support a role for adipose-derived mesenchymal stem cells (MSCs) in breast cancer progression; however, to date most studies have relied on adipose MSCs from non-breast sources. There is a particular need to investigate the role of adipose MSCs in the pathogenesis of basal-like breast cancer, which develops at a disproportionate rate in pre-menopausal African-American women with a gain in adiposity. The aim of this study was to better understand how breast adipose MSCs (bMSCs) contribute to the progression of basal-like breast cancers by relying on isogenic HMT-3255 S3 (pre-invasive) and T4-2 (invasive) human cells that upon transplantation into nude mice resemble this tumor subtype. In vitro results suggested that bMSCs may contribute to breast cancer progression in multiple ways. bMSCs readily penetrate extracellular matrix components in part through their expression of matrix metalloproteinases 1 and 3, promote the invasion of T4-2 cells and efficiently chemoattract endothelial cells via a bFGF-independent, VEGF-A-dependent manner. As mixed xenografts, bMSCs stimulated the growth, invasion and desmoplasia of T4-2 tumors, yet these resident stem cells showed no observable effect on the progression of pre-invasive S3 cells. While bMSCs form vessel-like structures within Matrigel both in vitro and in vivo and chemoattract endothelial cells, there appeared to be no difference between T4-2/bMSC mixed xenografts and T4-2 xenografts with regard to intra- or peri-tumoral vascularity. Collectively, our data suggest that bMSCs may contribute to the progression of basal-like breast cancers by stimulating growth and invasion but not vasculogenesis or angiogenesis.


Lesch-Nyhan disease.
Lesch-Nyhan disease is the most severe or complete phenotype of deficiency in hypoxanthineguanine phosphoribosyltransferase; other variant enzymes are found in patients without abnormality in behavior or mental development, and there are intermediate phenotypes in which enzyme activity is intermediate. A considerable number and variety of mutations in the HPRT gene have been discovered.


Multiple Evanescent White Dot Syndrome Following Intradermal Influenza Vaccination.
Purpose: To present a case report of MEWDS following an intradermal influenza vaccination. Methods: Review of the clinical, laboratory, photographic, and angiographic records of a patient with MEWDS. Results: 27-year-old female that presented to our clinic with photopsias OD. These symptoms began 2 weeks following an influenza intradermal vaccination. Fundus examination and diagnostic testing were consistent with MEWDS. Conclusion: While rare, MEWDS can occur following influenza vaccination.


[Two siblings with congenital adrenocortical unresponsiveness to ACTH showing peripheral neuropathy--morphometric evaluation of the sural nerve].
A 13-year-old boy, with the diagnosis of congenital adrenocortical unresponsiveness to ACTH (ACTH insensitivity) at age 7, developed a steppage gait, when under glucocorticoid replacement therapy at age 13. The parents were healthy and not consanguinous. On general physical examination, a mild diffuse skin hyperpigmentation was noted. Neurological examinations revealed that all the muscle stretch reflexes of both limbs were absent without pathologic reflexes. Pes cavus was found bilaterally. A slight decrease of tactile sensation was noted distal to the ankle joints. Pain sensation was slightly decreased in the toes. On laboratory examination, the conduction velocities of the left ulnar and median motor nerves were 51 and 45 m/sec, respectively, which are normal. No M-wave responses were obtained by electrical stimulation of the tibial and peroneal nerves. The coefficient of the variation of the R-R interval from ECG recordings was normal. Orthostatic hypotension was not observed. Achalasia was negative on the barium swallow esophagram. Therefore, it was concluded that he had motor and sensory polyneuropathy, and a right sural nerve biopsy was performed. A 12-year-old girl, a sister of the boy described above, with the diagnosis of ACTH insensitivity at age 5, noted a pain on the medial aspect of the left sole after skating. On general physical examination, a mild diffuse skin hyperpigmentation was discovered. On neurological examination, a spontaneous pain with dysesthesia was noted on the plantar aspect of the 1st, 2nd and 3rd left toes and on the anterior and medial aspect of the sole. Otherwise she was normal. A diagnosis of the left tarsal tunnel syndrome was made.(ABSTRACT TRUNCATED AT 250 WORDS)


Invasive Salmonellosis in Humans.
Human salmonellosis is generally associated with Salmonella enterica from subspecies enterica (subspecies I). Acute infections can present in one of four ways: enteric fever, gastroenteritis, bacteremia, or extraintestinal focal infection. As with other infectious diseases, the course and outcome of the infection depend on a variety of factors, including the infecting organism, the inoculating dose, and the immune status and genetic background of the host. For serovarsTyphi and Paratyphi A there is a clear association between the genetic background of the serovar and systemic infection in humans. For serovars Paratyphi B and Paratyphi C, a good clinical description of the host and detailed population genetics of the pathogen are necessary before more detailed genetic studies of novel virulence factors,or host factors,can be initiated. For the nontyphoidalserovars (NTS) the situation is less clear. Serovars Typhimurium and Enteritidis are the most common within the food chain, and so the large number of invasive infections associated with these serovars is most likely due to exposure rather than to increased virulence of the pathogen. In Africa, however, a closely related group of strains of serovar Typhimurium, associated with HIV infection, may have become host adapted tohumans, suggesting that not all isolates called "Typhimurium" should be considered as a single group. Here we review current knowledge of the salmonellae for which invasive disease in humans is an important aspect of their population biology.


Sustained Release of a Peptide-Based Matrix Metalloproteinase-2 Inhibitor to Attenuate Adverse Cardiac Remodeling and Improve Cardiac Function Following Myocardial Infarction.
Following myocardial infarction (MI), degradation of extracellular matrix (ECM) by upregulated matrix metalloproteinases (MMPs) especially MMP-2 decreases tissue mechanical properties, leading to cardiac function deterioration. Attenuation of cardiac ECM degradation at the early stage of MI has the potential to preserve tissue mechanical properties, resulting in cardiac function increase. Yet the strategy for efficiently preventing cardiac ECM degradation remains to be established. Current preclinical approaches have shown limited efficacy because of low drug dosage allocated to the heart tissue, dose-limiting side effects, and cardiac fibrosis. To address these limitations, we have developed a MMP-2 inhibitor delivery system that can be specifically delivered into infarcted hearts at early stage of MI to efficiently prevent MMP-2-mediated ECM degradation. The system was based on an injectable, degradable, fast gelation, and thermosensitive hydrogel, and a MMP-2 specific inhibitor, peptide CTTHWGFTLC (CTT). The use of fast gelation hydrogel allowed to completely retain CTT in the heart tissue. The system was able to release low molecular weight CTT over 4 weeks possibly due to the strong hydrogen bonding between the hydrogel and CTT. The release kinetics was modulated by amount of CTT loaded into the hydrogel, and using chondroitin sulfate and heparin that can interact with CTT and the hydrogel. Both glycosaminoglycans augmented CTT release, while heparin more greatly accelerated the release. After it was injected into the infarcted hearts for 4 weeks, the released CTT efficiently prevented cardiac ECM degradation as it not only increased tissue thickness but also preserved collagen composition similar to that in the normal heart tissue. In addition, the delivery system significantly improved cardiac function. Importantly, the delivery system did not induce cardiac fibrosis. These results demonstrate that the developed MMP-2 inhibitor delivery system has potential to efficiently reduce adverse myocardial remodeling and improve cardiac function.


T-cell lymphoma with abundant CD20 expression showing a good response to rituximab with gemcitabine, oxiplatin, and L-asparaginase (R-pGEMOX): A case report.
T-cell lymphoma is a neoplasm that expresses markers of T-cell or natural killer cell (NK)-origin but not those of B-cell origin. Although B-cell lymphoma with abundant expression of T-cell markers exist, the opposite is very rare. Therefore, little is known about this subtype of lymphoma, including its treatment and prognosis. A 65-year-old man was diagnosed with T-cell lymphoma with abundant CD20 expression. He was refractory to cyclophosphamide + epirubicin + vincristine + prednisone + etoposide (CHOPE), ifosfamide + cisplatin + etoposide + dexamethasone (DICE), and hyper-cyclophosphamide + vincristine + epirubicin + dexamethasone (CVAD) chemotherapy. The patient was also treated with prednisone + thalidomide + chidamide, which was also not effective. Upon admission to our department, he was administered a rituximab + gemcitabine + oxiplatin + L-asparaginase (R-pGEMOX) regimen and achieved partial remission. CD20-positive T-cell lymphoma is a very rare type of lymphoma that is refractory to CHOP-like regimens alone. Rituximab may be effective in patients showing abundant CD20 expression, and an R-pGEMOX regimen will likely be effective, even in refractory/recurrent patients.


Sp1 and p73 activate PUMA following serum starvation.
p53-upregulated modulator of apoptosis (PUMA) plays an essential role in p53-dependent apoptosis following DNA damage. PUMA also mediates apoptosis independent of p53. In this study, we investigated the role and mechanism of PUMA induction in response to serum starvation in p53-deficient cancer cells. Following serum starvation, the binding of Sp1 to the PUMA promoter significantly increased, whereas inhibition of Sp1 completely abrogated PUMA induction. p73 was found to be upregulated by serum starvation and mediate PUMA induction through the p53-binding sites in the PUMA promoter. Sp1 and p73beta appeared to cooperatively activate PUMA transcription, which is inhibited by the phosphoinsitide 3-kinase (PI3K)-protein kinase B (AKT) pathway. Furthermore, knockdown of PUMA suppressed serum starvation-induced apoptosis in leukemia cells. Our results suggest that transcription factors Sp1 and p73 mediate p53-independent induction of PUMA following serum starvation to trigger apoptosis in human cancer cells.


Bayesian Inference Approach to Quantify Primary and Secondary Organic Carbon in Fine Particulate Matter Using Major Species Measurements.
The determination of primary organic carbon (POC) and secondary organic carbon (SOC) in fine particulate matter using ambient measurements is essential in atmospheric chemistry. A novel Bayesian inference (BI) approach is proposed to achieve such quantification using only major component measurement data and tested in two case studies. One case study composes of filter-based daily compositional data made in the Pearl River Delta region, China, during 2012, while the other uses online measurement data recorded at the Dianshan Lake monitoring site in Shanghai in wintertime 2019. Source-specific organic trace measurement data are available in both the cases so that positive matrix factorization (PMF) analysis is performed, where PMF-resolved POC and SOC are used as the best available reference values for model evaluation. Meanwhile, traditional techniques, i.e., minimum ratio value, minimum R squared, and multiple linear regression, are also employed and evaluated. For both the cases, the BI models have shown significant advantages in accurately estimating POC and SOC amounts over conventional methods. Further analysis suggests that using sulfate as the SOC tracer in BI model gives the best model performance. This methodological advance provides an improved and practical tool to derive POC and SOC levels for addressing PM-related environmental impacts.


Discernment scheme for paraquat poisoning: A five-year experience in Shiraz, Iran.
To evaluate various schemes for paraquat poisoning and different variables that influence the outcome of acute paraquat poisoning. In a cross-sectional study, the information about all cases of acute paraquat poisoning who were admitted to teaching hospitals affiliated to Shiraz University of Medical Sciences, in a five year period (September 2010 to September 2015) were evaluated. The variables included: Demographic data, medical assessment, therapeutic options, laboratory findings, and the outcomes. Data were analyzed using SPSS, version 22. Significant difference between groups was tested using t-test for continues outcomes and χ2 test for categorical. The significance level was considered to be P < 0.05. A total of 104 patients (66.3% male) were evaluated. The mean age of the female patients was 22.81 ± 9.87 years and the male patients' was 27.21 ± 11.06 years. Ninety seven (93.3%) of all the cases were suicide attempts with mortality rate of 43.2%. Despite the necessity for emergency hemodialysis during the first 6 h of intoxication, none of the patients had dialysis during this time. Immunosuppressive and corticosteroid medications were not administrated in adequate dosage in 31.1% and 60% of the patients, respectively. Ingestion of more than 22.5 cc of paraquat and increase in creatinine level were the most important predictors of mortality. Treatment should start immediately for these patients. Moreover, creating a clinical guideline according to the findings can have an impact on the treatment procedure which seems to be necessary.


Multi-allergen screening immunoassay for the detection of protein markers of peanut and four tree nuts in chocolate.
A multiresidue enzyme immunoassay was developed to check for the presence of markers of peanut, hazelnut, almond, cashew and Brazil nuts in a single run. The assay was designed under the competitive indirect format and adapted for screening purposes applied to chocolate samples. The limit of detection for this assay was below 1 microg g-1 protein for each allergenic food. In most cases, the high specificity of the antibodies used allowed the identification of each particular allergenic food with no possible confusion. This assay was proven to be useful as part of an analytical procedure involving the identification of the unknown allergenic food among peanut and other tree nuts in recalled samples before the application of a quantitative technique to determine the level of cross-contamination.


Effect of tetrahedral DNA nanostructures on osteogenic differentiation of mesenchymal stem cells via activation of the Wnt/β-catenin signaling pathway.
Adipose-derived stem cells (ADSCs) are considered to be ideal stem cell sources for bone regeneration owing to their ability to differentiate into osteo-like cells. Therefore, they have attracted increasing attention in recent years. Tetrahedral DNA nanostructures (TDNs), a new type of DNA-based biomaterials, have shown great potential for biomedical applications. In the present work, we aimed to investigate the role played by TDNs in osteogenic differentiation and proliferation of ADSCs and tried to explore if the canonical Wnt signal pathway could be the vital biological mechanism driving these cellular responses. Upon exposure to TDNs, ADSCs proliferation and osteogenic differentiation were significantly enhanced, accompanied by the up-regulation of genes correlated with the Wnt/β-catenin pathway. In conclusion, our results indicate that TDNs are crucial regulators of the increase in osteogenic potential and ADSCs proliferation, and this noteworthy discovery could provide a promising novel approach toward ADSCs-based bone defect regeneration.


Obesity, adipocytokines, and insulin resistance in breast cancer.
The adipocytokines are biologically active polypeptides that are produced either exclusively or substantially by the adipocytes, and act by endocrine, paracrine, and autocrine mechanisms. Most have been associated with obesity, hyperinsulinaemia, type 2 diabetes, and chronic vascular disease; in addition, six adipocytokines--vascular endothelial growth factor, hepatocyte growth factor, leptin, tumour necrosis factor-alpha, heparin-binding epidermal growth factor-like growth factor, and interleukin-6--promote angiogenesis while one, adiponectin, is inhibitory. Obesity and insulin resistance have both been identified as risk factors for breast cancer and are associated with late-stage disease and poor prognosis. Angiogenesis is essential for breast cancer development and progression, and so it is plausible that obesity-related increases in adipocytokine production and a reduction in adiponectin may adversely affect breast cancer outcome by their angiogenesis-related activities. There is also experimental evidence that some adipocytokines can act directly on breast cancer cells to stimulate their proliferation and invasive capacity. Thus, adipocytokines may provide a biological mechanism by which obesity and insulin resistance are causally associated with breast cancer risk and poor prognosis. Both experimental and clinical studies are needed to develop this concept, and particularly in oestrogen-independent breast cancers where preventive and therapeutic options are limited.


Systematic evaluation of cancer risk associated with DNMT3B polymorphisms.
The aim of our study is to provide a precise quantification for the association between DNA methyltransferase 3B (DNMT3B) variations (rs2424913 C/T, rs1569686 G/T, rs6087990 T/C and rs2424908 T/C) and the risk of cancer. We performed a systematic literature review and assessed the methodological quality of included case-control designed studies based on Newcastle-Ottawa Scale. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to assess the strengths of the associations. We identified 34 studies for pooled analyses. Overall, the results demonstrated that rs2424913 polymorphism was significantly associated with negative cancer risk in the African population (CT vs TT: OR 0.10, 95% CI 0.02-0.63, P = 0.01; CT+CC vs TT: OR 0.14, 95% CI 0.03-0.76, P = 0.02), and the rs1569686 polymorphism was significantly associated with a subtly decreased cancer risk (GT vs TT: OR 0.80, 95% CI 0.72-0.90, P < 0.01; GT+GG vs TT: OR 0.84, 95% CI 0.76-0.94, P < 0.01), particularly in the Asian population (GT vs TT: OR 0.79, 95% CI 0.66-0.96, P < 0.01) and in colorectal cancer subgroup (G vs T: OR 0.69, 95% CI 0.54-0.88, P < 0.01). In addition, the rs6087990 polymorphism was associated with decreased risk in Asian population (T vs C: OR 0.77, 95% CI 0.62-0.96, P = 0.02). Similarly, the rs2424908 polymorphism was observed as a protective factor for cancer in the Asian population (CT+CC vs TT: OR 0.79, 95% CI 0.66-0.95, P = 0.01). DNMT3B polymorphisms might be associated with decreased cancer risk especially in the Asian population and for colorectal cancer. Further multicentric studies are still needed to confirm the results.


[18F]Fluorodeoxyglucose-positron emission tomography/computed tomography response evaluation can predict histological response at surgery after induction chemotherapy for oligometastatic bladder cancer.
Patients with limited metastatic and locally advanced bladder cancer have a poor prognosis, and no definite treatment recommendations exist. However, long-term survival is possible for selected patients if surgery is combined with multiple courses of chemotherapy (i.e. induction chemotherapy). Patients with tumours that are insensitive to chemotherapy probably have little to gain from subsequent extensive surgery. The aim of this study was to evaluate sequential FDG-PET/CT examinations as an indicator of chemotherapy response. Between 2007 and 2015, 50 patients with oligometastatic invasive bladder cancer selected for induction chemotherapy underwent two FDG-PET/CT examinations: the first before the start of chemotherapy and the second after three courses of cisplatinum-based combination chemotherapy. Responders were given up to six courses of chemotherapy. FDG-PET/CT response was correlated with histological response in excised lymph-node metastases. Three patients showed progression to incurable disease during chemotherapy and another two patients did not undergo surgery, for medical reasons. Lymphadenectomy was performed in the remaining 45 patients, of whom 43 had lymph-node metastasis. FDG-PET/CT prediction of the histological nodal chemotherapy response was correct in 37 (86%) of those 43. The second FDG-PET/CT examination identified four out of nine non-responders. For response, the sensitivity, specificity, and positive and negative predictive values for FDG-PET/CT accuracy were 37 out of 37 (100%), one out of six (17%), 37 out of 42 (88%) and one out of one (100%), respectively. Repeated FDG-PET/CT seems to predict histological response. However, with the histological response criteria used in this study, five non-responders were not identified by the second FDG-PET/CT investigation.