Emerging Therapeutic Potential of Cannabidiol (CBD) in Neurological Disorders: A Comprehensive Review.
Cannabidiol (CBD), derived from Cannabis sativa, has gained remarkable attention for its potential therapeutic applications. This thorough analysis explores the increasing significance of CBD in treating neurological conditions including epilepsy, multiple sclerosis, Parkinson's disease, and Alzheimer's disease, which present major healthcare concerns on a worldwide scale. Despite the lack of available therapies, CBD has been shown to possess a variety of pharmacological effects in preclinical and clinical studies, making it an intriguing competitor. This review brings together the most recent findings on the endocannabinoid and neurotransmitter systems, as well as anti-inflammatory pathways, that underlie CBD's modes of action. Synthesized efficacy and safety assessments for a range of neurological illnesses are included, covering human trials, in vitro studies, and animal models. The investigation includes how CBD could protect neurons, control neuroinflammation, fend off oxidative stress, and manage neuronal excitability. This study emphasizes existing clinical studies and future possibilities in CBD research, addressing research issues such as regulatory complications and contradicting results, and advocates for further investigation of therapeutic efficacy and ideal dose methodologies. By emphasizing CBD's potential to improve patient well-being, this investigation presents a revised viewpoint on its suitability as a therapeutic intervention for neurological illnesses.


A New Repellent for Redbay Ambrosia Beetle (Coleoptera: Curculionidae: Scolytinae), Primary Vector of the Mycopathogen That Causes Laurel Wilt.
The redbay ambrosia beetle, Xyleborus glabratus, was detected in Georgia, USA, in 2002 and has since spread to 11 additional states. This wood-boring weevil carries a symbiotic fungus, Harringtonia lauricola, that causes laurel wilt, a lethal disease of trees in the Lauraceae family. Native ambrosia beetles that breed in infected trees can acquire H. lauricola and contribute to the spread of laurel wilt. Since 2002, laurel wilt has devastated native Persea species in coastal forests and has killed an estimated 200,000 avocado trees in Florida. Since laurel wilt is difficult to manage once it has entered a susceptible agrosystem, this study evaluated piperitone as a candidate repellent to deter attacks by X. glabratus and other ambrosia beetles. Additionally, piperitone was compared to the known repellent verbenone as a potential cost-effective alternative. The repellent efficacy was determined by comparing captures in traps baited with commercial beetle lures containing α-copaene versus captures in traps baited with lures plus a repellent. In parallel 10-week field tests, the addition of piperitone reduced the captures of X. glabratus in α-copaene-baited traps by 90%; however, there was no significant reduction in the captures of native ambrosia beetles in ethanol-baited traps. In two replicate 10-week comparative tests, piperitone and verbenone both reduced X. glabratus captures by 68-90%, with longevity over the full 10 weeks. This study identifies piperitone as a new X. glabratus repellent with potential for pest management.


Microanatomical considerations for the fenestration of the septum pellucidum.
The anatomical foundations for the endoscopic fenestration of the septum pellucidum have not been presented previously in an isolated fashion. Using a surgical microscope, the microsurgical anatomy of the septum pellucidum, lateral ventricles, and surrounding structures was examined in ten adult brains injected with silicone rubber. The mean anteroposterior length of the septum pellucidum was 41 mm (range 40-42). Its mean height was 13.11 mm (range 12-15) at the level of the foramen of Monro; 10 mm (range 9-11) at the frontal horns, and 8 mm (range 7-10) at the ventricular atrium. One to three septal veins delimited 2 or 3 avascular areas in the septum pellucidum. We found an anterior area which was consistently avascular and large enough to be fenestrated safety. More posterior areas, while avascular, were inconsistent in their size and shape.


Ultrasound-Induced Bubble Clusters in Tissue-Mimicking Agar Phantoms.
Therapeutic ultrasound can drive bubble activity that damages soft tissues. To study the potential mechanisms of such injury, transparent agar tissue-mimicking phantoms were subjected to multiple pressure wave bursts of the kind being considered specifically for burst wave lithotripsy. A high-speed camera recorded bubble activity during each pulse. Various agar concentrations were used to alter the phantom's mechanical properties, especially its stiffness, which was varied by a factor of 3.5. However, the maximum observed bubble radius was insensitive to stiffness. During 1000 wave bursts of a candidate burst wave lithotripsy treatment, bubbles appeared continuously in a region that expanded slowly, primarily toward the transducer. Denser bubble clouds are formed at higher pulse repetition frequency. The specific observations are used to inform the incorporation of damage mechanisms into cavitation models for soft materials.


Epigenetic Regulation of Vascular Smooth Muscle Cell Phenotype Switching in Atherosclerotic Artery Remodeling: A Mini-Review.
Atherosclerosis is a chronic inflammatory disease characterized by extensive remodeling of medium and large-sized arteries. Inward remodeling (=lumen shrinkage) of the vascular walls is the underlying cause for ischemia in target organs. Therefore, inward remodeling can be considered the predominant feature of atherosclerotic pathology. Outward remodeling (=lumen enlargement) is a physiological response compensating for lumen shrinkage caused by neointimal hyperplasia, but as a pathological response to changes in blood flow, outward remodeling leads to substantial arterial wall thinning. Thinned vascular walls are prone to rupture, and subsequent thrombus formation accounts for the majority of acute cardiovascular events. Pathological remodeling is driven by inflammatory cells which induce vascular smooth muscle cells to switch from quiescent to a proliferative and migratory phenotype. After decades of intensive research, the molecular mechanisms of arterial remodeling are starting to unfold. In this mini-review, we summarize the current knowledge of the epigenetic and transcriptional regulation of vascular smooth muscle cell phenotype switching from the contractile to the synthetic phenotype involved in arterial remodeling and discuss potential therapeutic options.


Thrombopoietin stimulates migration and activates multiple signaling pathways in hepatoblastoma cells.
Thrombopoietin (TPO), a cytokine that participates in the differentiation and maturation of megakaryocytes, is produced in the liver, but only limited information is available on the biological response of liver-derived cells to TPO. In this study, we investigated whether HepG2 cells express c-Mpl, the receptor for TPO, and whether TPO elicits biological responses and intracellular signaling in this cell type. Specific transcripts for c-Mpl were detected in HepG2 cells by RT-PCR, and expression of the protein was demonstrated by Western blot analysis and immunofluorescence. Exposure of HepG2 cells to TPO was associated with a dose-dependent increase in cell migration and chemoinvasion through Matrigel-coated filters. A checkerboard analysis showed that the effects of TPO on cell migration were dependent on both chemotaxis and chemokinesis. Exposure of HepG2 cells to TPO resulted in the activation of different members of the MAPK family, including ERK and JNK, as assessed using phosphorylation-specific antibodies and immune complex kinase assays. TPO also activated phosphatidylinositol 3-kinase (PI3K) and the downstream kinase Akt in a time-dependent manner. Finally, activation of c-Mpl was associated with increased activation of nuclear factor-kappaB. With the use of specific inhibitors, tyrosine phosphorylation and activation of PI3K were found to be required for the induction of migration in response to TPO. We conclude that TPO exerts biological actions on cultured hepatoblastoma cells via activation of c-Mpl and its downstream signaling.


3D-Printed Column with Porous Monolithic Packing for Online Solid-Phase Extraction of Multiple Trace Metals in Environmental Water Samples.
In this study, we used a multimaterial three-dimensional printing (3DP) technology and porous composite filaments (Lay-Fomm, Gel-Lay, and Lay-Felt) to fabricate solid phase extraction (SPE) columns for the enhanced extraction of multiple metal ions. When employed as sample pretreatment devices in an automatic flow injection analysis/inductively coupled plasma mass spectrometry (ICP-MS) system, these 3D-printed SPE columns performed the near-complete extractions of Mn, Co, Ni, Cu, Zn, Cd, and Pb ions from natural water samples prior to ICP-MS determination. After optimizing the column fabrication, the extraction conditions, and the automatic analysis system, the column packed with the porous composite Lay-Fomm 40 was found to provide the highest extraction performance-the extraction efficiencies of the listed metal ions were all greater than 99.2%, and the detection limits of the method ranged from 0.3 to 6.7 ng L-1. The detection of these metal ions in several reference materials (CASS-4, SLEW-3, 1640a, and 1643f) validated the reliability of this method; spike analyses of collected water samples (groundwater, river water, and seawater) demonstrated the applicability of the method. The nature of the printing materials enhanced the analytical performance of 3D-printed sample pretreatment devices. Such approaches will be useful to diversify the range of sample preparation schemes and analytical methods enabled by 3DP technologies.


Cubic aromaticity in ligand-stabilized doped Au superatoms.
The magnetic response of valence electrons in doped gold-based M@Au8L8 q superatoms (M = Pd, Pt, Ag, Au, Cd, Hg, Ir, and Rh; L = PPh3; and q = 0, +1, +2) is studied by calculating the gauge including magnetically induced currents (GIMIC) in the framework of the auxiliary density functional theory. The studied systems include 24 different combinations of the dopant, total cluster charge, and cluster structure (cubic-like or oblate). The magnetically induced currents (both diatropic and paratropic) are shown to be sensitive to the atomic structure of clusters, the number of superatomic electrons, and the chemical nature of the dopant metal. Among the cubic-like structures, the strongest aromaticity is observed in Pd- and Pt-doped M@Au8L8 0 clusters. Interestingly, Pd- and Pt-doping increases the aromaticity as compared to a similar all-gold eight-electron system Au9L8 +1. With the recent implementation of the GIMIC in the deMon2k code, we investigated the aromaticity in the cubic and butterfly-like M@Au8 core structures, doped with a single M atom from periods 5 and 6 of groups IX-XII. Surprisingly, the doping with Pd and Pt in the cubic structure increases the aromaticity compared to the pure Au case not only near the central atom but encompassing the whole metallic core, following the aromatic trend Pd > Pt > Au. These doped (Pd, Pt)@Au8 nanoclusters show a closed shell 1S21P6 superatom electronic structure corresponding to the cubic aromaticity rule 6n + 2.


Propidium Monoazide Improves Quantification of Resting Spores of Plasmodiophora brassicae with qPCR.
Plasmodiophora brassicae, which causes clubroot of Brassica crops, persists in soil as long-lived resting spores. Quantitative polymerase chain reaction (qPCR) analysis is often used to quantify resting spores but does not distinguish between DNA of viable and nonviable spores. The impact of pretreating spores with propidium monoazide (PMA), which inhibits amplification of DNA from nonviable microorganisms, was assessed in several experiments. Spore suspensions from immature and mature clubs were heat treated; then, PMA-PCR analyses and bioassays were performed to assess spore viability. Prior to heat treatment, assessments comparing PMA-PCR to qPCR for mature spores were similar, indicating that most of these spores were viable. However, only a small proportion (<26%) of immature spores were amplified in PMA-PCR. Bioassays demonstrated that clubroot severity was much higher in plants inoculated with mature spores than with immature spores. Heat treatment produced little or no change in estimates of mature spores from qPCR but spore estimates from PMA-PCR and clubroot severity in bioassays were both substantially reduced. Estimates of spore concentration with PMA-PCR were less consistent for immature spores. To facilitate use of PMA-PCR on infested soil, a protocol for extracting spores from soil was developed that provided higher extraction efficiency than the standard methods.


Accuracy of the Surgeons' Clinical Prediction of Postoperative Major Complications Using a Visual Analog Scale.
Although the risk factors that contribute to postoperative complications are well recognized, prediction in the context of a particular patient is more difficult. We were interested in using a visual analog scale (VAS) to capture surgeons' prediction of the risk of a major complication and to examine whether this could be improved. The study was performed in 3 stages. In phase I, the surgeon assessed the risk of a major complication on a 100-mm VAS immediately before and after surgery. A quality control questionnaire was designed to check if the VAS was being scored as a linear scale. In phase II, a VAS with 6 subscales for different areas of clinical risk was introduced. In phase III, predictions were completed following the presentation of detailed feedback on the accuracy of prediction of complications. In total, 1295 predictions were made by 58 surgeons in 859 patients. Eight surgeons did not use a linear scale (6 logarithmic, 2 used 4 categories of risk). Surgeons made a meaningful prediction of major complications (preoperative median score 40 mm for complications v. 22 mm for no complication, P < 0.001; postoperative 46 mm v. 21 mm, P < 0.001). In phase I, the discrimination of prediction for preoperative (0.778), postoperative (0.810), and POSSUM (Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity) morbidity (0.750) prediction was similar. Although there was no improvement in prediction with a multidimensional VAS, there was a significant improvement in the discrimination of prediction after feedback (preoperative, 0.895; postoperative, 0.918). Awareness of different ways a VAS is scored is important when designing and interpreting studies. Clinical assessment of major complications by the surgeon was initially comparable to the prediction of the POSSUM morbidity score and improved significantly following the presentation of clinically relevant feedback.


Role of rigidity on the activity of proteinase inhibitors and their peptide mimics.
The Bowman-Birk inhibitors (BBIs) are a family of proteins that share a canonical loop structure whose presence in a conserved conformation is linked to their inhibitory activity. We study the conformational properties of the canonical loop using a graph theoretical approach as implemented in the floppy inclusions and rigid substructure topography (FIRST). We find that the canonical loop is an independent rigid cluster in the natural inhibitors. We have further used this technique to identify residues that play an important role in the structural rigidity of the protein by quantifying their contribution to the overall rigidity of the inhibitor. We find that the conserved elements among the natural and synthetic peptides are the ones that contribute the most to rigidity, even if they are located far from the active site, as rigidity effects are nonlinear and hence nonlocal. The results help to elucidate why certain mutations in the loop of the BBI produce peptides that fail to have the designed inhibitory activity.


The Potential of Overlayers on Tin-based Perovskites for Water Splitting.
Photoelectrochemical water splitting is a promising method of clean hydrogen production for green energy uses. Here, we report on a tin-based oxide perovskite combined with an overlayer that shows enhanced bifunctional hydrogen and oxygen evolution. In our first-principles study of tin-based perovskites, based upon density functional theory, we investigate how the formation of a surface affects the electronic properties of these materials. We show that the best candidate, SrSnO3, possesses hydrogen and oxygen overpotentials of 0.75 and 0.72 eV, respectively, which are reduced to 0.35 and 0.54 eV with the inclusion of a ZrO2 overlayer. Furthermore, this overlayer promotes charge extraction, stabilizes the reaction pathways, and improves the band gap such that it straddles the overpotentials between pH 0 and pH 12. This result indicates that SrSnO3 with a ZrO2 overlayer has significant potential as a highly efficient bifunctional water splitter for producing hydrogen and oxygen gas on the same surface.


Depletion of pulmonary intravascular macrophages inhibits acute lung inflammation.
Pulmonary intravascular macrophages (PIMs) are present in ruminants and horses. These species are highly sensitive to acute lung inflammation compared with non-PIM-containing species such as rats and humans. There is evidence that rats and humans may also recruit PIMs under certain conditions. We investigated precise contributions of PIMs to acute lung inflammation in a calf model. First, PIMs were recognized with a combination of in vivo phagocytic tracer Monastral blue and postembedding immunohistology with anti-CD68 monoclonal antibody. Second, gadolinium chloride depleted PIMs within 48 h of treatment (P < 0.05). Finally, PIMs contain TNF-alpha, and their depletion reduces cells positive for IL-8 (P < 0.05) and TNF-alpha (P < 0.05) and histopathological signs of acute lung inflammation in calves infected with Mannheimia hemolytica. The majority of IL-8-positive inflammatory cells in lung septa of infected calves were platelets. Platelets from normal cattle contained preformed IL-8 that was released upon in vitro exposure to thrombin (P < 0.05). These novel data show that PIMs, as the source of TNF-alpha, promote recruitment of inflammatory cells including IL-8-containing platelets to stimulate acute inflammation and pathology in lungs. These data may also be relevant to humans due to our ability to recruit PIMs.


Oculopharyngeal muscular dystrophy as a paradigm for muscle aging.
Symptoms in late-onset neuromuscular disorders initiate only from midlife onward and progress with age. These disorders are primarily determined by identified hereditable mutations, but their late-onset symptom manifestation is not fully understood. Here, we review recent research developments on the late-onset autosomal dominant oculopharyngeal muscular dystrophy (OPMD). OPMD is caused by an expansion mutation in the gene encoding for poly-adenylate RNA binding protein1 (PABPN1). The molecular pathogenesis for the disease is still poorly understood. Despite a ubiquitous expression of PABPN1, symptoms in OPMD are limited to skeletal muscles. We discuss recent studies showing that PABPN1 levels in skeletal muscles are lower compared with other tissues, and specifically in skeletal muscles, PABPN1 expression declines from midlife onward. In OPMD, aggregation of expanded PABPN1 causes an additional decline in the level of the functional protein, which is associated with severe muscle weakness in OPMD. Reduced PABNPN1 expression in muscle cell culture causes myogenic defects, suggesting that PABPN1 loss-of-function causes muscle weakness in OPMD and in the elderly. Molecular signatures of OPMD muscles are similar to those of normal muscle aging, although expression trends progress faster in OPMD. We discuss a working hypothesis that aging-associated factors trigger late-onset symptoms in OPMD, and contribute to accelerated muscle weakness in OPMD. We focus on the pharyngeal and eyelid muscles, which are often affected in OPMD patients. We suggest that muscle weakness in OPMD is a paradigm for muscle aging.


Peculiar snoring in patients with multiple system atrophy: its sound source, acoustic characteristics, and diagnostic significance.
It is known that abductor paralysis (AP) of the vocal folds sometimes occurs in patients with multiple system atrophy (MSA), and some of them have sleep apnea and loud snoring during sleep. However, the site of obstruction and the sound source of the snoring are still unknown. We performed fiberscopic examinations under diazepam sedation in 8 MSA patients with AP and analyzed the snoring sound. We found that the peculiar snoring occurred with inspiratory vibration of the vocal folds, and there was no obstruction in this portion. Acoustic analysis showed that the fundamental frequency of vocal fold snoring was 260 to 330 Hz, which is different from that of ordinary soft palate snoring. Recognition of vocal fold snoring is important in the early diagnosis of MSA and sleep-related breathing disorders.


Simultaneous Distinction of Monospecific and Mixed DFS70 Patterns During ANA Screening with a Novel HEp-2 ELITE/DFS70 Knockout Substrate.
Systemic autoimmune connective tissue disorders are characterized by circulating antinuclear antibodies (ANA). Although there are several technologies available for ANA screening, indirect immunofluorescence (IIF) using Human epithelial cells-2 (HEp-2) substrate remains the primary and recommended method because of its superior sensitivity. HEp-2 substrates can detect a multitude of patterns resulting from autoantibody binding to various protein and nucleic acid autoantigens distributed throughout the nucleus and cytoplasm of the cells. The great diversity of monospecific and mixed patterns resulting from positive reactions on HEp-2 substrate also complicate the interpretation and accuracy of reporting. One specific example which received utmost attention recently is the dense fine speckled 70 (DFS70) pattern resulting from autoantibodies that specifically bind to a protein called lens epithelium derived growth factor (LEDGF). Lack of clear association with a specific systemic autoimmune disease and high prevalence in healthy populations have made accurate interpretation of DFS70 pattern important. Accurate distinction of DFS70 pattern from disease-associated patterns using conventional HEp-2 substrate is challenging. Moreover, frequent co-occurrence of DFS70 pattern along with disease-associated patterns such as homogeneous, speckled, and mixed homogeneous-speckled patterns complicate the IIF interpretation. The goal of this paper is to demonstrate the utility of a novel engineered HEp-2 IIF substrate that retains all advantages of conventional HEp-2 substrate while simultaneously providing the ability to distinguish DFS70 pattern with high confidence in both monospecific and mixed ANA positive examples. The new substrate is further able to unmask disease-associated ANA patterns previously concealed by DFS70 pattern.


Reversible tubular lesion in pregnancy-induced hypertension detected by urinary beta 2-microglobulin.
Serum and urine beta 2-microglobulin concentrations were measured in 17 primigravidas with mild pregnancy-induced hypertension and nine normotensive control patients matched for gestational age. Serum beta 2-microglobulin and creatinine clearance values were not different between the two groups but urinary excretion of beta 2-microglobulin was three times higher in the hypertensive patients. This difference disappeared within seven days of delivery. These results indicate that a reversible renal tubular lesion occurs in pregnancy-induced hypertension even in the absence of detectable proteinuria.


Structural analysis of a bacterial UDP-sugar 2-epimerase reveals the active site architecture before and after catalysis.
The sugar, 2,3-diacetamido-2,3-dideoxy-d-mannuronic acid, was first identified ∼40 years ago in the O-antigen of Pseudomonas aeruginosa O:3,a,d. Since then, it has been observed on the O-antigens of various pathogenic Gram-negative bacteria including Bordetella pertussis, Escherichia albertii, and Pseudomonas mediterranea. Previous studies have established that five enzymes are required for its biosynthesis beginning with uridine dinucleotide (UDP)-N-acetyl-d-glucosamine (UDP-GlcNAc). The final step in the pathway is catalyzed by a 2-epimerase, which utilizes UDP-2,3-diacetamido-2,3-dideoxy-d-glucuronic acid as its substrate. Curious as to whether this biochemical pathway is found in extreme thermophiles, we examined the published genome sequence for Thermus thermophilus HB27 and identified five ORFs that could possibly encode for the required enzymes. The focus of this investigation is on the ORF WP_011172736, which we demonstrate encodes for a 2-epimerase. For this investigation, ten high resolution X-ray crystallographic structures were determined to resolutions of 2.3 Å or higher. The models have revealed the manner in which the 2-epimerase anchors its UDP-sugar substrate as well as its UDP-sugar product into the active site. In addition, this study reveals for the first time the manner in which any sugar 2-epimerase can simultaneously bind UDP-sugars in both the active site and the allosteric binding region. We have also demonstrated that the T. thermophilus enzyme is allosterically regulated by UDP-GlcNAc. Whereas the sugar 2-epimerases that function on UDP-GlcNAc have been the focus of past biochemical and structural analyses, this is the first detailed investigation of a 2-epimerase that specifically utilizes UDP-2,3-diacetamido-2,3-dideoxy-d-glucuronic acid as its substrate.


Quantitative proteomic and lipidomics analyses of high oil content GmDGAT1-2 transgenic soybean illustrate the regulatory mechanism of lipoxygenase and oleosin.
Proteomic and lipidomics analyses of WT and GmDGAT1-2 transgenic soybeans showed that GmDGAT1-2 over-expression induced lipoxygenase down-regulatation and oleoin up-regulatation, which significantly changed the compositions and total fatty acid. The main goal of soybean breeding is to increase the oil content. Diacylglycerol acyltransferase (DGAT) is a key rate-limiting enzyme in fatty acid metabolism and may regulate oil content. Herein, 10 GmDGAT genes were isolated from soybean and transferred into wild-type (WT) Arabidopsis. The total fatty acid was 1.2 times higher in T3 GmDGAT1-2 transgenic Arabidopsis seeds than in WT. Therefore, GmDGAT1-2 was transferred into WT soybean (JACK), and four T3 transgenic soybean lines were obtained. The results of high-performance gas chromatography and Soxhlet extractor showed that, compared with those of JACK, oleic acid (18:1), and total fatty acid levels in transgenic soybean plants were much higher, but linoleic acid (18:2) was lower than WT. Palmitic acid (16:0), stearic acid (18:0), and linolenic acid (18:3) were not significantly different. For mechanistic studies, 436 differentially expressed proteins (DEPs) and 180 differentially expressed metabolites (DEMs) were identified between WT (JACK) and transgenic soybean pods using proteomic and lipidomics analyses. Four lipoxygenase proteins were down-regulated in linoleic acid metabolism while four oleosin proteins were up-regulated in the final oil formation. The results showed an increase in the total fatty acid and 18:1 composition, and a decrease in the 18:2 composition of fatty acid. Our study brings new insights into soybean genetic transformation and the deep study of molecular mechanism that changes the total fatty acid, 18:1, and 18:2 compositions in GmDGAT1-2 transgenic soybean.


Inhibitory synaptic plasticity: spike timing-dependence and putative network function.
While the plasticity of excitatory synaptic connections in the brain has been widely studied, the plasticity of inhibitory connections is much less understood. Here, we present recent experimental and theoretical findings concerning the rules of spike timing-dependent inhibitory plasticity and their putative network function. This is a summary of a workshop at the COSYNE conference 2012.


Perforated duodenal ulcer in a pediatric patient with eosinophilic gastroenteritis.
An 11-year-old boy with eosinophilic gastroenteritis treated by an elimination diet alone presented with a perforated gastroduodenal ulcer subsequent to blunt trauma to the abdomen. Peripheral eosinophilia, chronic iron deficiency, chronic hypoalbuminemia and severe failure to thrive had been present since age 2 years. Immunological work-up revealed food allergies, documented by skin tests. A review of the literature since 1966 revealed only six other cases of perforation of the gastrointestinal tract, one of whom was also a child.


Monolithic Mid-Infrared Integrated Photonics Using Silicon-on-Epitaxial Barium Titanate Thin Films.
Broadband mid-infrared (mid-IR) photonic circuits that integrate silicon waveguides and epitaxial barium titanate (BTO) thin films are demonstrated using the complementary metal-oxide-semiconductor process. The epitaxial BTO thin films are grown on lanthanum aluminate (LAO) substrates by the pulsed laser deposition technique, wherein a broad infrared transmittance between λ = 2.5 and 7 μm is observed. The optical waveguiding direction is defined by the high-refractive-index amorphous Si (a-Si) ridge structure developed on the BTO layer. Our waveguides show a sharp fundamental mode over the broad mid-IR spectrum, whereas its optical field distribution between the a-Si and BTO layers can be modified by varying the height of the a-Si ridge. With the advantages of broad mid-IR transparency and the intrinsic electro-optic properties, our monolithic Si on a ferroelectric BTO platform will enable tunable mid-IR microphotonics that are desired for high-speed optical logic gates and chip-scale biochemical sensors.


Additive Effects of Quorum Sensing Anti-Activators on Pseudomonas aeruginosa Virulence Traits and Transcriptome.
In the opportunistic pathogen Pseudomonas aeruginosa, quorum sensing (QS) via acyl-homoserine lactone (AHL) signals coordinates virulence gene expression. AHL signals must reach a critical threshold before enough is bound by cognate regulators LasR and RhlR to drive transcription of target genes. In addition, three anti-activator proteins, QteE, QscR, and QslA, sequester QS regulators to increase the threshold for induction and delay expression of QS target genes. It remains unclear how multiple anti-activators work together to achieve the quorum threshold. Here, we employed a combination of mutational, kinetic, phenotypic, and transcriptomic analysis to examine regulatory effects and interactions of the three distinct anti-activators. We observed combinatorial, additive effects on QS gene expression. As measured by reporter gene fusion, individual deletion of each anti-activator gene increased lasB expression and QS-controlled virulence factor production. Deletion of qslA in combination with the deletion of any other anti-activator gene resulted in the greatest increase and earliest activation of lasB gene expression. Western analysis revealed that relative increases in soluble LasR in anti-activator mutants correlate with increased lasB expression and QS-controlled virulence factor production. RNA-seq of the previously uncharacterized QslA and QteE regulons revealed overlapping, yet distinct groups of differentially expressed genes. Simultaneous inactivation of qteE and qslA had the largest effect on gene expression with 999 genes induced and 798 genes repressed in the double mutant vs. wild-type. We found that LasR and RhlR-activated QS genes formed a subset of the genes induced in the qteE, qslA, and double mutant. The activation of almost all of these QS genes was advanced from stationary phase to log phase in the qteE qslA double mutant. Taken together, our results identify additive effects of anti-activation on QS gene expression, likely via LasR and RhlR, but do not rule out QS-independent effects.


From Discovery of Snake Venom Disintegrins to A Safer Therapeutic Antithrombotic Agent.
Snake venoms affect blood coagulation and platelet function in diverse ways. Some venom components inhibit platelet function, while other components induce platelet aggregation. Among the platelet aggregation inhibitors, disintegrins have been recognized as unique and potentially valuable tools for examining cell-matrix and cell-cell interactions and for the development of antithrombotic and antiangiogenic agents according to their anti-adhesive and anti-migration effect on tumor cells and antiangiogenesis activities. Disintegrins represent a family of low molecular weight, cysteine-rich, Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing polypeptides, which inhibit fibrinogen binding to integrin αIIbβ3 (i.e., platelet glycoprotein IIb/IIIa), as well as ligand binding to integrins αvβ3, and α5β1 expressed on cells (i.e., fibroblasts, tumor cells, and endothelial cells). This review focuses on the current efforts attained from studies using disintegrins as a tool in the field of arterial thrombosis, angiogenesis, inflammation, and tumor metastasis, and briefly describes their potential therapeutic applications and side effects in integrin-related diseases. Additionally, novel R(K)GD-containing disintegrin TMV-7 mutants are being designed as safer antithrombotics without causing thrombocytopenia and bleeding.


Morning blood pressure surge is associated with carotid intima-media thickness in prehypertensive patients.
Morning blood pressure (BP) surge (MBPS) is defined as an excessive increase in the morning BP from the lowest systolic BP during sleep and is reported as a risk factor for cardiovascular events in current clinical studies. In this study, we aimed to investigate the relationship between MBPS and carotid intima-media thickness (C-IMT) in prehypertensive patients. We evaluated the association between the rate of BP variation derived from ambulatory BP monitoring and C-IMT in patients with prehypertension. One hundred and seventy patients with prehypertension were included in the study. All office BP measurements and ambulatory 24-h, day-time, and night-time measurements were similar between each group. C-IMT [0.60 (range: 0.57-0.65) vs. 0.55 (range: 0.50-0.60) cm; P<0.001] and the mean platelet volume [8.7 (range: 7.9-9.1) vs. 7.9 (range: 7.3-8.8) fl; P=0.002] were significantly higher in the greater MBPS group than the lower group. In multivariate analysis, male sex [odds ratio (OR): 2.271, confidence interval (CI): 1.011-5.100, P=0.047], greater MBPS (OR: 8.474, CI: 3.623-19.608, P<0.001), and elevated mean platelet volume levels (OR: 3.359, CI: 1.978-5.705, P<0.001) were found to be independent predictors of greater C-IMT in prehypertensive patients. Our study suggests that greater MBPS is associated independently with C-IMT in prehypertensive patients.


[Presence of a new Trichostrongyloidea (Nematoda) Nochtia (Nochtia) atelerixi n. sp. in an Erinacoidea (Insectivora) in Togo].
Nochtia (Nochtia) atelerixi n. sp. (Nematoda, Trichostrongyloidea) of Ethiopian Erinacoidea. - Nochtia (Nochtia) atelerixi n. sp. is found in the intestine of the hedgehog Atelerix albiventris in Togo. It is distinguished from the two other congeneric species parasite of asiatic Primates, N. (N.) nochti Travassos et Vogelsang, 1929 and N. (N.) tani Le Van Hoa, 1966, mainly by the highest number of cuticular crests and spicules with six tips.


Optical binary image encryption using aperture-key and dual wavelengths.
We described a method where the secret binary image that has been encoded into a single amplitude pattern in Fresnel domain can be recovered based on phase retrieval with an aperture-key and wavelength keys, and no holographic recording is needed in the encryption. The predesigned aperture-key not only realizes the intensity modulation of the encrypted image, but also helps to retrieve the secret image with high quality. All the necessary decryption keys can be kept in digital form that facilitates data transmission and loading in image retrieval process. Numerical simulation results are given for testing the validity and security of the proposed approach.


Hydration prevents chronic hyperglycaemic patients from neurological deterioration post-ischaemic stroke.
To determine whether chronic hyperglycaemia predisposes patients to dehydration, which may promote neurological deterioration, and to investigate whether dehydration control improves functional outcome. This study included 355 patients hospitalized with acute ischaemic stroke and diabetes mellitus who fulfilled the glycaemic gap ≤0. We used the following cut-offs: (i) no chronic hyperglycaemia (glycated haemoglobin A1c [HbA1c] < 7%) and (ii) chronic hyperglycaemia (HbA1c ≥ 7%). The chronic hyperglycaemic patients were randomly divided into the control group and the hydration group. Hydration therapy was only initiated in the hydration group. The blood urea nitrogen (BUN)/creatinine (Cr) ratio was used as an indicator of dehydration. Stroke severity on admission and discharge was assessed by means of National Institutes of Health Stroke Scale (NIHSS). The mean baseline BUN/Cr ratios were higher in the control group and hydration group than in the no chronic hyperglycaemia group. The mean BUN/Cr ratio decreased from 91.22 ± 29.95 on the first day to 77.03 ± 18.23 on the third day (P < .001) in the hydration group. On the third day after admission, there was no significant difference in the BUN/Cr ratio between the hydration group and the no chronic hyperglycaemia group (P = .831). Moreover, neurological deterioration was highest in the control group (33.6%, 36/107), followed by the hydration group (10.5%, 11/105) and the no chronic hyperglycaemia group (5.6%, 8/143). Chronic hyperglycaemia was associated with the admission NIHSS score and neurological deterioration after excluding the effect of stress hyperglycaemia. Furthermore, hydration therapy may help prevent neurological deterioration.


Socioeconomic Predictors of Treatment Outcomes Among Adults With Major Depressive Disorder.
In this study, the authors sought to examine the impact of socioeconomic variables on outcomes of pharmacotherapy treatments for major depressive disorder in analyses that controlled for treatment access and level of care. The authors used data from the Combining Medications to Enhance Depression Outcomes study, a prospective clinical trial conducted from March 2008 to April 2014 with 665 adults who had major depressive disorder and were randomly assigned to three pharmacotherapeutic treatments, to develop Bayesian hierarchical models of treatment trajectories for change in Quick Inventory of Depressive Symptomatology-Self-Report ratings. Posterior tail probabilities were used to evaluate the effects of education, income, race-ethnicity, and employment on treatment outcomes. After sex, age, and treatment type were controlled for in the analyses, not having a college education (<16 years of schooling), being unemployed, or being non-White were each associated with slower and less improvement. At the end of treatment (week 12), not having a college degree reduced treatment responses by 9.6% (p=0.045), being unemployed by 6.6% (p=0.007), and being non-White by 11.3% (p<0.001). Treatment response was significantly related to income; having an income at the 25th percentile of the income distribution decreased improvement by 4.8% compared with having an income at the 75th percentile (p=0.018). Within a short-term, randomized controlled trial, socioeconomic factors had a critical role in the acute response of patients to pharmacotherapy for major depression.


Hydrogen Sulfide Triggered Charge-Reversal Micelles for Cancer-Targeted Drug Delivery and Imaging.
Currently, the development of polymeric micelles combining diagnosis and targeted therapy is theoretically and practically significant in cancer treatment. In addition, it has been reported that cancer cells can produce large amounts of hydrogen sulfide (H2S) and their survival depends on the content of H2S. In this study, a series of N-(2-hydroxyethyl)-4-azide-1,8-naphthalimide ended amphiphilic diblock copolymer poly(2-hydroxyethyl methacrylate)-block-poly(methyl methacrylate) (N3-Nap-PHEMA-b-PMMA-N3) micelles were prepared. Around cancer tissues, the N3-Nap-PHEMA45-b-PMMA42-N3 micelles exhibited dual characteristics of monitoring H2S and H2S triggered charge reversal with the reduction of the azido group. The surface charge of N3-Nap-PHEMA45-b-PMMA42-N3 micelles reversed from negative to positive after monitoring H2S. With H2S triggered charge reversal, the cellular uptake of DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles was effectively enhanced through electrostatic attraction mediated targeting, and a fast doxorubicin (DOX) release rate was observed. The MTT assay demonstrated that N3-Nap-PHEMA45-b-PMMA42-N3 micelles were biocompatible to HeLa cells, and DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles showed enhanced cytotoxicity in HeLa cells in the presence of H2S. Furthermore, in vivo fluorescence imaging and biodistribution experiments revealed that DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles could provide good tumor imaging and accumulate in tumor tissue. Therefore, N3-Nap-PHEMA45-b-PMMA42-N3 micelles can be used as a promising platform for tumor diagnosis and therapy.


Bile acid distributions, sex-specificity, and prognosis in colorectal cancer.
Bile acids are known to be genotoxic and contribute to colorectal cancer (CRC). However, the link between CRC tumor bile acids to tumor location, patient sex, microbiome, immune-regulatory cells, and prognosis is not clear. We conducted bile acid analysis using targeted liquid chromatography-mass spectrometry (LC-MS) on tumor tissues from CRC patients (n = 228) with survival analysis. We performed quantitative immunofluorescence (QIF) on tumors to examine immune cells. Twelve of the bile acids were significantly higher in right-sided colon tumors compared to left-sided colon tumors. Furthermore, in male patients, right-sided colon tumors had elevated secondary bile acids (deoxycholic acid, lithocholic acid, ursodeoxycholic acid) compared to left-sided colon tumors, but this difference between tumors by location was not observed in females. A high ratio of glycoursodeoxycholic to ursodeoxycholic was associated with 5-year overall survival (HR = 3.76, 95% CI = 1.17 to 12.1, P = 0.026), and a high ratio of glycochenodeoxycholic acid to chenodeoxycholic acid was associated with 5-year recurrence-free survival (HR = 3.61, 95% CI = 1.10 to 11.84, P = 0.034). We also show correlation between these bile acids and FoxP3 + T regulatory cells. This study revealed that the distribution of bile acid abundances in colon cancer patients is tumor location-, age- and sex-specific, and are linked to patient prognosis. This study provides new implications for targeting bile acid metabolism, microbiome, and immune responses for colon cancer patients by taking into account primary tumor location and sex.


The human renin kidney enhancer is required to maintain base-line renin expression but is dispensable for tissue-specific, cell-specific, and regulated expression.
Renin is the rate-limiting enzyme in the renin-angiotensin system and thus dictates the level of the pressor hormone angiotensin-II. The classical site of renin expression and secretion is the renal juxtaglomerular cell, where its expression is tightly regulated by physiological cues. An evolutionarily conserved transcriptional enhancer located 11 kb upstream of the human RENIN gene has been reported to markedly enhance transcription in renin expressing cells in vitro. However, its importance in vivo remains unclear. We tested whether this enhancer is required for appropriate tissue- and cell-specific expression, or for physiological regulation of the human RENIN gene. To accomplish this, we used a retrofitting technique employing homologous recombination in bacteria to delete the enhancer from a 160-kb P1-artificial chromosome containing human RENIN, two upstream genes and one downstream gene, and then generated two lines of transgenic mice. We previously showed that human renin expression in transgenic mice containing the wild type construct is tightly regulated as is expression of the linked genes. Deletion of the enhancer had no effect on tissue-specific expression of human RENIN, but using the downstream gene as an internal control, found that human RENIN mRNA levels were 3-10-fold decreased compared with constructs containing the enhancer. Despite this decrease in expression, renin protein remained localized to renal juxtaglomerular cells and was appropriately regulated by cues that either increase or decrease expression of renin. Our results suggest that sequences other than the enhancer may be necessary for tissue-specific, cell-specific, and regulated expression of human RENIN.


Synthesis and molecular tumbling properties of sialyl Lewis X and derived neoglycolipids.
The sialyl Lewis X (sLeX) epitope has become a prominent target for biological studies because of its role in inflammation through binding to selectins. This epitope is located at the terminal end in glycosphingolipids and a lactose unit serves as spacer to the ceramide moiety. This paper focuses on the influence of the spacer structure and spacer length in regard to the mobility of the sLeX epitope. To this end sLex neoglycolipids 1a-c, with one, two, or three lactose units as spacer between the sLeX tetrasaccharide epitope and the membrane anchor, were synthesized. The synthetic strategy was also applied to the synthesis of the corresponding Lewis X (LeX) derivatives. The glycolipids were inserted in model membranes, and the tumbling frequencies of the sLex tetrasaccharide epitopes were then analysed by NMR spectroscopy. A nonaethylene glycol spacer decouples the carbohydrate moiety from the membrane mobility while (oligo-)lactoses act as more rigid distance keepers between the Lewis epitope and the surface of the membrane. Quantification of the different degrees of decoupling was possible by analysis of rotational correlation times.


Lobe transport analysis of the Kelvin-Stuart cat's eyes driven flow.
Mixing and transport in the driven Kelvin-Stuart cat's eyes dynamical system is studied using lobe transport theory and the topological approximation method (TAM). The application of the TAM also provides a global bifurcation analysis. Lobe areas are calculated using the Melnikov amplitude function, which has been derived for the Kelvin-Stuart system. Results indicate that regions, originally in the exterior above the vortex chain, can be transported to the exterior below the vortex chain (and vice versa) by passing through the interior, and that a region within the interior of a given vortex can be transported to the interior of a neighboring vortex, or the interior of a vortex several vortices distant from the given vortex. Cumulative transport is shown to decrease with increasing perturbation frequency for a fixed value of perturbation strength. Cumulative transport increases with increasing perturbation strength for a fixed value of the structure index L. Cumulative transport approaches a characteristic maximum value for each set of parameter values. Results demonstrate a linear dependence of the maximum cumulative transport upon a universal flux function of the form proposed by Rom-Kedar and Poje, suggesting a possible scaling in the transport dependent on the structure index L.


Developing an interdisciplinary and cross-sectoral community of practice in the domain of forests and livelihoods.
Although significant resources are being spent researching and fostering the relationship between forests and livelihoods to promote mutually beneficial outcomes, critical gaps in understanding persist. A core reason for such gaps is that researchers, practitioners, and policy makers lack the structured space to interact and collaborate, which is essential for effective, interdisciplinary research, practice, and evaluation. Thus, scientific findings, policy recommendations, and measured outcomes have not always been synthesized into deep, systemic understanding; learning from practice and implementation does not easily find its way into scientific analyses, and science often fails to influence policy. Communities of practice (CofPs) are dynamic sociocultural systems that bring people together to share and create knowledge around a common topic of interest. They offer participants a space and structure within which to develop new, systemic approaches to multidimensional problems on a common theme. Uniquely informed by a systems-thinking perspective and drawing from the scientific and gray literatures and in-depth interviews with representatives of established CofPs in the natural resource management and development domain, we argue that a well-designed and adequately funded CofP can facilitate interdisciplinary and cross-sectoral relationships and knowledge exchange. Well-designed CofPs integrate a set of core features and processes to enhance individual, collective, and domain outcomes; they set out an initial but evolving purpose, encourage diverse leadership, and promote collective-identity development. Funding facilitates effective communication strategies (e.g., in person meetings). We urge our colleagues across sectors and disciplines to take advantage of CofPs to advance the domain of forests and livelihoods.


Looking for childhood schizophrenia: case series of false positives.
Extensive experience with the diagnosis of childhood-onset schizophrenia indicates a high rate of false positives. Most mislabeled patients have chronic disabling, affective, or behavioral disorders. The authors report the cases of three children who passed stringent initial childhood-onset schizophrenia "screens" but had no chronic psychotic disorder. For two, the European literature yielded more fitting diagnoses: psychosis not otherwise specified (e.g., reactive or psychogenic psychosis, paranoid schizophrenia), single episode in full remission (e.g., anxiety psychosis), and factitious disorder (DSM-IV 300.16). These cases illustrate that transient psychotic illnesses can be misdiagnosed as childhood-onset schizophrenia. Proper identification can prevent years of inappropriate therapies.


Identification of MAGEC2/CT10 as a High Calcium-Inducible Gene in Triple-Negative Breast Cancer.
The expression of the melanoma/cancer-testis antigen MAGEC2/CT10 is restricted to germline cells, but like most cancer-testis antigens, it is frequently upregulated in advanced breast tumors and other malignant tumors. However, the physiological cues that trigger the expression of this gene during malignancy remain unknown. Given that malignant breast cancer is often associated with skeletal metastasis and co-morbidities such as cancer-induced hypercalcemia, we evaluated the effect of high Ca2+ on the calcium-sensing receptor (CaSR) and potential mechanisms underlying the survival of triple-negative breast cancer (TNBC) cells at high Ca2+. We show that chronic exposure of TNBC cells to high Ca2+ decreased the sensitivity of CaSR to Ca2+ but stimulated tumor cell growth and migration. Furthermore, high extracellular Ca2+ also stimulated the expression of early response genes such as FOS/FOSB and a unique set of genes associated with malignant tumors, including MAGEC2. We further show that the MAGEC2 proximal promoter is Ca2+ inducible and that FOS/FOSB binds to this promoter in a Ca2+- dependent manner. Finally, downregulation of MAGEC2 strongly inhibited the growth of TNBC cells in vitro. These data suggest for the first time that MAGEC2 is a high Ca2+ inducible gene and that aberrant expression of MAGEC2 in malignant TNBC tissues is at least in part mediated by an increase in circulating Ca2+via the AP-1 transcription factor.


The in-vivo assessment of Turkish propolis and its nano form on testicular damage induced by cisplatin.
Chemotherapeutic drugs, such as cisplatin (CP), which are associated with oxidative stress and apoptosis, may adversely affect the reproductive system. This study tests whether administration of propolis and nano-propolis (NP) can alleviate oxidative stress and apoptosis in rats with testicular damage induced by CP. In this study, polymeric nanoparticles including propolis were synthesized with a green sonication method and characterized using Fourier transform-infrared spectroscopy, Brunauer-Emmett-Teller, and wet scanning transmission electron microscopy techniques. In total, 56 rats were divided into the following seven groups: control, CP, propolis, NP-10, CP + propolis, CP + NP-10, and CP + NP-30. Propolis (100 mg/kg), NP-10 (10 mg/kg), and NP-30 (30 mg/kg) treatments were administered by gavage daily for 21 d, and CP (3 mg/kg) was administered intraperitoneally in a single dose. After the experiment, oxidative stress parameters, namely, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT), and apoptotic pathways including B cell leukemia/lymphoma-2 protein (Bcl-2) and Bcl-2-associated X protein (Bax) were measured in testicular tissues. Furthermore, sperm quality and weights of the testis, epididymis, right cauda epididymis, seminal vesicles and prostate were evaluated. Propolis and NP (especially NP-30) were able to preserve oxidative balance (decreased MDA levels and increased GSH, CAT, and GPx activities) and activate apoptotic pathways (decreased Bax and increased Bcl-2) in the testes of CP-treated rats. Sperm motility in the control, CP, and CP + NP-30 groups were 60%, 48.75%, and 78%, respectively (P < 0.001). Especially, NP-30 application completely corrected the deterioration in sperm features induced by CP. The results show that propolis and NP treatments mitigated the side effects of CP on spermatogenic activity, antioxidant situation, and apoptosis in rats.


Reduction of amphotericin B nephrotoxicity with mannitol.
Amphotericin B in combination with mannitol was given to a patient who had mucocutaneous candidiasis and moderate renal insufficiency. Previously, amphotericin B alone had induced an abrupt increase in serum creatinine and urea nitrogen, but when mannitol was given concurrently there was no worsening of renal function. Thus, amphotericin B with mannitol appears to offer a less nephrotoxic but equally candicidal therapeutic regimen in the renal compromised patient requiring parenteral candicidal therapy.


Suppressive effect of triethyllead on entry of proteins into the CNS myelin sheath in vitro.
Incorporation of [14C]leucine into the myelin sheath was studied in brain stem slices prepared from 22-day-old rats. Individual major myelin proteins were separated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. There was a time lag before incorporation of the label into proteolipid protein (PLP) and intermediate protein (IP) reached maximal rates. Labelling of basic proteins (BP) and Wolfgram proteins (WP) revealed a much shorter lag in entry. Appearance of radioactive proteins in the myelin sheath was significantly hampered by triethyllead (PbEt3) added to the incubation medium at micromolar concentrations. Inhibition values were highest in the case of PLP and were closely followed by the values for IP. BP and WP were less inhibited, although incorporation of these proteins into myelin was still suppressed more than was synthesis of total homogenate protein. Thus, myelin -forming cells seem to be unduly vulnerable to the toxin relative to the rest of the tissue. Furthermore, the results indicate an interference of PbEt3 with certain posttranslational process involved in furnishing of integral myelin proteins.


Fatty Acid and Stable Carbon Isotope Composition of Slovenian Milk: Year, Season, and Regional Variability.
This study examined the percentage and stable isotope ratios of fatty acids in milk to study seasonal, year, and regional variability. A total of 231 raw cow milk samples were analyzed. Samples were taken twice per year in 2012, 2013, and 2014, in winter and summer, covering four distinct geographical regions in Slovenia: Mediterranean, Alpine, Dinaric, and Pannonian. A discriminant analysis model based on fatty acid composition was effective in discriminating milk according to the year/season of production (86.9%), while geographical origin discrimination was less successful (64.1%). The stable isotope composition of fatty acids also proved to be a better biomarker of metabolic transformation processes in ruminants than discriminating against the origin of milk. Further, it was observed that milk from Alpine and Mediterranean regions was healthier due to its higher percentage of ω-3 polyunsaturated fatty acid and conjugated linoleic acid.


Toll-like receptor 2- and MyD88-dependent phosphatidylinositol 3-kinase and Rac1 activation facilitates the phagocytosis of Listeria monocytogenes by murine macrophages.
Toll-like receptors (TLRs) play a key role in the innate immune response by sensing bacterial ligands. The mechanisms involved in the TLR-mediated cytokine response are well established; however, the possible contribution of TLR-dependent recognition of bacteria to macrophage phagocytosis remains unclear. Listeria monocytogenes is an intracellular, parasitic, Gram-positive bacterium recognized mainly by TLR2. In this study, we investigated whether TLR2-dependent signaling is involved in the phagocytosis of L. monocytogenes by macrophages. We found no difference in the number of L. monocytogenes cells associating with wild-type (WT) and TLR2(-/-) macrophages 1 h after infection. However, the number of L. monocytogenes cells phagocytosed in TLR2(-/-) and MyD88(-/-) macrophages was significantly lower than that of WT macrophages. In addition, lipopolysaccharide (LPS) treatment restored impaired phagocytic activity of TLR2(-/-) macrophages but did not enhance the activity of MyD88(-/-) macrophages. The efficiency of phagocytosis was suppressed by inhibitors of phosphatidylinositol 3-kinase (PI3K) and the small Rho GTPases but not by cycloheximide. Moreover, functional activation of PI3K and Rac1 was impaired in TLR2(-/-) and MyD88(-/-) macrophages. In an in vivo infection model, we found significantly lower numbers of L. monocytogenes cells phagocytosed in peritoneal macrophages of TLR2(-/-) and MyD88(-/-) mice after intraperitoneal infection. Moreover, a lower number of bacteria were detected in the spleens of TLR2(-/-) mice 1 day after intravenous infection than in WT mice. These results clearly indicated that TLR2-MyD88-dependent signaling enhances the basal level of phagocytosis of L. monocytogenes by macrophages through activation of PI3K and Rac1, not by synthesis of proinflammatory cytokines or expression of phagocytic receptors.


Characterization of the bacterial microbiome in first-pass meconium using propidium monoazide (PMA) to exclude nonviable bacterial DNA.
Numerous studies have reported bacterial DNA in first-pass meconium samples, suggesting that the human gut microbiome is seeded prior to birth. However, these studies have not been able to discriminate between DNA from living bacterial cells, DNA from dead bacterial cells or cell-free DNA. Here we have used propidium monoazide (PMA) together with 16S rRNA gene sequencing to determine whether there are intact bacterial cells in the fetal gut. DNA was extracted from first-pass meconium (n = 5) and subjected to 16S rRNA gene sequencing with/without PMA treatment. All meconium samples, regardless of PMA treatment, contained detectable levels of bacterial DNA; however, treatment with PMA prior to DNA extraction decreased the DNA yield by approximately 20%. PMA-treated meconium samples did not differ significantly from untreated samples in terms of observed number of OTUs (P = 0·945); although they did differ taxonomically, with around one quarter of OTUs identified in untreated samples only, suggesting that they have originated from cell-free/nonviable DNA. The mean Sørensen coefficient for treated vs untreated samples was 0·527. Our findings suggest that the fetal gut is seeded with intact bacterial cells prior to birth. This is an important finding, as exposure to live bacteria during gestation might have a significant impact on the developing fetus. SIGNIFICANCE AND IMPACT OF THE STUDY: DNA-based microbiome studies performed using 16S rRNA gene sequencing are limited by their inability to discriminate between live bacterial cells, dead bacterial cells and cell-free DNA. Here we use propidium monoazide (PMA) to exclude nonviable bacteria from microbiome analysis of first-pass meconium samples and thereby reveal that the majority of the purported fetal gut microbiome is from intact bacterial cells. This work demonstrates the importance of excluding nonviable bacteria when analysing the microbial community in low-biomass samples such as meconium.


A diagnostic challenge: anterior variant of mandibular lingual bone depression.
Mandibular lingual bone depressions are considered to be developmental anomalies and most clinicians are familiar with the posterior variant (known as Stafne's bone cavity) that occurs in lingual mandibular molar regions, adjacent to the submandibular gland and below the mandibular canal. The anterior variant of the mandibular lingual bone depression is an asymptomatic bone cavity that occurs adjacent to the sublingual gland in the anterior mandible. Radiographically, it appears as a well-corticated radiolucency that retains a normal trabecular pattern internally. CT imaging is diagnostic and avoids surgical and sialographic procedures. This article reviews radiographic and CT features of a case involving the anterior variant of mandibular lingual bone depression.


Increased incidence of adjuvant arthritis in Wistar rats.
The moderate incidence of arthritis in Wistar rats after inoculation of a suspension of Mycobacterium butyricum in oil increased to nearly 100% by two modifications. Inoculation with 4 week- as compared to 1 week-cultured. M. butyricum raised the incidence from 34 to 63%. Inoculation of this more arthritogenic material into the F1-descendants of M. butyricum sensitive parents raised the incidence of 96%. Also the severity of the arthritis in rats selected in that manner was higher than in non-selected rats. Treatment of arthritic rats of either source with phenylbutazone resulted in a comparable dose-related reduction of the diameters of the hind-limbs. Mating of rats with various degrees of arthritic response showed that sensitivity transmission to the F1-descendants was optimal with the most sensitive parents. Although the exact nature of the transmission has not been defined, the uniform and higher sensitivity of thus selected rats is of great value for quantitative pharmacological studies.


The depressor action of dopamine and adrenaline.
Dopamine is a pressor agent in the spinal cat, but causes a fall of blood pressure in the guinea-pig and rabbit under urethane anaesthesia. When guinea-pigs and rabbits are injected with reserpine, which depletes the vessel walls of noradrenaline, dopamine then becomes pressor. If an intravenous infusion of noradrenaline is given the depressor action returns. An intravenous infusion of vasopressin does not have this effect.A strip of rabbit aorta is caused to contract by noradrenaline and by dopamine, but if dopamine is added at the height of a noradrenaline contraction it causes relaxation.Adrenaline causes a fall of blood pressure in the cat under ether with vagi cut. However, in a reserpine-treated cat its action is pressor. The depressor action is restored during an infusion of noradrenaline. Noradrenaline has thus been shown to cause a vasomotor reversal of dopamine and of adrenaline.


Size-corrected BMD decreases during peak linear growth: implications for fracture incidence during adolescence.
Peak adolescent fracture incidence at the distal end of the radius coincides with a decline in size-corrected BMD in both boys and girls. Peak gains in bone area preceded peak gains in BMC in a longitudinal sample of boys and girls, supporting the theory that the dissociation between skeletal expansion and skeletal mineralization results in a period of relative bone weakness. The high incidence of fracture in adolescence may be related to a period of relative skeletal fragility resulting from dissociation between bone expansion and bone mineralization during the growing years. The aim of this study was to examine the relationship between changes in size-corrected BMD (BMDsc) and peak distal radius fracture incidence in boys and girls. Subjects were 41 boys and 46 girls measured annually (DXA; Hologic 2000) over the adolescent growth period and again in young adulthood. Ages of peak height velocity (PHV), peak BMC velocity (PBMCV), and peak bone area (BA) velocity (PBAV) were determined for each child. To control for maturational differences, subjects were aligned on PHV. BMDsc was calculated by first regressing the natural logarithms of BMC and BA. The power coefficient (pc) values from this analysis were used as follows: BMDsc = BMC/BA(pc). BMDsc decreased significantly before the age of PHV and then increased until 4 years after PHV. The peak rates in radial fractures (reported from previous work) in both boys and girls coincided with the age of negative velocity in BMDsc; the age of peak BA velocity (PBAV) preceded the age of peak BMC velocity (PBMCV) by 0.5 years in both boys and girls. There is a clear dissociation between PBMCV and PBAV in boys and girls. BMDsc declines before age of PHV before rebounding after PHV. The timing of these events coincides directly with reported fracture rates of the distal end of the radius. Thus, the results support the theory that there is a period of relative skeletal weakness during the adolescent growth period caused, in part, by a draw on cortical bone to meet the mineral demands of the expanding skeleton resulting in a temporary increased fracture risk.


Acute retinal detachment induced by the Valsalva manoeuvre in morning glory disc anomaly.
We present a case in which a large, bullous, predominantly inferior, serous retinal detachment developed acutely after the Valsalva manoeuvre (from a coughing fit) in an eye with morning glory disc anomaly. We postulate that a rapid alteration in intracranial pressure was transmitted through the cavitary disc defect. This allowed a sudden influx of cerebrospinal fluid and/or liquefied vitreous into the subretinal space. This previously unreported case provides important evidence for the role of intracranial pressure fluctuations in the pathogenesis of macular schisis and neurosensory detachment secondary to optic disc cavitations.


Infertile polycystic ovary syndrome patients undergoing in vitro fertilization with the gonadotropin-releasing hormone-antagonist protocol: role of hyperandrogenism.
This retrospective cohort study is to assess the effects of hyperandrogenism (HA) in polycystic ovary syndrome (PCOS) patients with gonadotropin-releasing hormone (GnRH)-antagonist protocol during in vitro fertilization (IVF). Total 892 infertile Patients between 20 and 35 years of age with normal body mass index (BMI, 18.50 -24.99 kg/m2), including those with tubal factor infertility (control, n = 318), PCOS infertility with HA (HA PCOS, n = 244), and PCOS infertility without HA (non-HA PCOS, n = 330), were included. Number of retrieved oocytes was significantly higher and total Gonadotropin consumption was significant lower in the HA PCOS group, whereas abortion rate was significantly higher and live birth rate was significantly lower in the HA PCOS group, compared with the control and non-HA PCOS groups. In the HA PCOS group, the number of available embryos tended to be higher with no significance. The GnRH-antagonist protocol is more suitable for HA PCOS patients, with lower cost and more number of embryos available for transfer. Due to the high abortion rate and low live birth rate, a freeze-all approach might be a preferable option for HA PCOS patients so as to create a buffer for reducing androgen levels before transferring freeze-thawed embryos.


Enhancing cancer clonality analysis with integrative genomics.
It is understood that cancer is a clonal disease initiated by a single cell, and that metastasis, which is the spread of cancer from the primary site, is also initiated by a single cell. The seemingly natural capability of cancer to adapt dynamically in a Darwinian manner is a primary reason for therapeutic failures. Survival advantages may be induced by cancer therapies and also occur as a result of inherent cell and microenvironmental factors. The selected "more fit" clones outmatch their competition and then become dominant in the tumor via propagation of progeny. This clonal expansion leads to relapse, therapeutic resistance and eventually death. The goal of this study is to develop and demonstrate a more detailed clonality approach by utilizing integrative genomics. Patient tumor samples were profiled by Whole Exome Sequencing (WES) and RNA-seq on an Illumina HiSeq 2500 and methylation profiling was performed on the Illumina Infinium 450K array. STAR and the Haplotype Caller were used for RNA-seq processing. Custom approaches were used for the integration of the multi-omic datasets. Reported are major enhancements to CloneViz, which now provides capabilities enabling a formal tumor multi-dimensional clonality analysis by integrating: i) DNA mutations, ii) RNA expressed mutations, and iii) DNA methylation data. RNA and DNA methylation integration were not previously possible, by CloneViz (previous version) or any other clonality method to date. This new approach, named iCloneViz (integrated CloneViz) employs visualization and quantitative methods, revealing an integrative genomic mutational dissection and traceability (DNA, RNA, epigenetics) thru the different layers of molecular structures. The iCloneViz approach can be used for analysis of clonal evolution and mutational dynamics of multi-omic data sets. Revealing tumor clonal complexity in an integrative and quantitative manner facilitates improved mutational characterization, understanding, and therapeutic assignments.


Probing the visible luminescence mechanism in ZnO nanoparticles by band edge modulation.
The visible luminescence mechanism of ZnO is an important but controversial problem. In this paper, we report the structural and optical properties of Mg-doped ZnO nanoparticles (approximately 3-4 nm) synthesized via the sol-gel method. X-ray diffraction (XRD) analysis and absorption spectra observations revealed that Mg ions replace Zn ions in the lattice. In the room temperature photoluminescence (PL) spectra, three emission bands, ultraviolet (UV), blue, and green, were observed. With increasing concentration of Mg, the near band edge (NBE) emission band progressively shifted to the higher energy side. The green emission in the visible emission band, however, presented an inconspicuous shift. The reason is probably that the bottom of the conduction band in ZnO is determined by the Zn 4s state, and the top of the valence band is determined by the O 2p state. Mg ions in ZnO substitute for zinc ions and enter a slightly distorted tetrahedral site, which causes the bottom of the ZnO conduction band to be shifted to higher energy and leaves the top of the valence band unchanged. This combined with the fact that the deep level position is insensitive to the shift of the band edge led us to conclude that the green emission originates from electronic transition between the deep defect level and the top of the valence band (or very shallow acceptor level).


[Vaccination against malaria. Disappointments and hopes].
After the first in vitro cultivation of Plasmodium falciparum 21 years ago, the prospect of anti-malarial vaccination arose many hopes, but, in the end, it so far has mainly given rise to doubts and disappointments. Technically, the problem is particularly difficult. Plasmodium falciparum has a very complex antigenic structure with several hundreds, if not several thousands, of different epitopes for each of the four main evolutive stages of the parasite (sporozoites, merozoites, gametocytes, ookinetes) which correspond to different phase of the infection and could be a target for vaccination. Many of these epitopes are stage-specific and some of them vary from one strain to another. Adjuvants also play a major role and can qualitatively modify the type of immune response. The immune mechanisms also differ according to the final goal: anti-Plasmodium infection or anti-disease vaccine. Over the last few years, the first clinical assays have been carried out with the Spf66 vaccine, a synthetic complex protein directed against sporozoites and merozoites. In adults and children, the first results in South America and in East Africa were modest but encouraging. Unfortunately they were not confirmed by further studies in West Africa and South-East Asia. Two new types of vaccines are under preliminary clinical evaluation. One is directed against ookinetes of Plasmodium falciparum (Pfs25 and Pfs28) and can stop the transmission from the mosquito. The other is an anti-sporozoite vaccine with a new immunogen (RTS,S) in which the circumsporozoite protein is fused to the hepatitis B surface antigen and can protect against infestation. New prospects and improvements are offered by the technique of DNA vaccines and will probably also result from better knowledge of cellular and molecular biology of the parasite which is being extensively studied (genomic structure). If new promising perspectives exist, it is particularly important to be careful to avoid such disappointments as those caused, in the past, by a too-optimistic and over-publicized presentation of some preliminary results. It is now certain that one or several malaria-vaccines will be available, but no one can seriously say when, for whom and how. In any case, it is unrealistic to hope that vaccine(s) alone will be able to eradicate such an epidemiologically complex disease as malaria. It is probable that only the coordinated use of all the techniques available (anti-vectorial protection and fight, chemoprophylaxis and chemotherapy, vaccination) will lead to success.


[Changes in spontaneous blast transformation of children's lymphocytes which have been observed in vitro in the last years].
In the Immunology Department of the Institute of Mother and Child in Warsaw we have used lymphocyte blastic transformation test (LETT) over 30 years to study lymphocyte function. During the last 10 years we have noticed progressive elevation of lymphocyte percentage undergoing spontaneous blast transformation (autotransformation) in culture of these cells. The percentage rose from mean value of 2.5% to 14.7% in year 2000 with statistically significant difference already between 1985 and 1990 (2.5% versus 9.3%). The reason for this phenomenon is unknown and needs more investigations.


Trelagliptin Mitigates Macrophage Infiltration by Preventing the Breakdown of the Blood-Brain Barrier in the Brain of Middle Cerebral Artery Occlusion Mice.
Stroke is a significant cardiovascular disease that influences the health of human beings all over the world, especially the elderly population. It is reported that the blood-brain barrier (BBB) can be easily destroyed by stroke, which is one of the main factors responsible for macrophage infiltration and central nervous inflammation. Here, we report the protective effects of Trelagliptin against BBB injury and macrophage infiltration. Our results indicate that the infraction volume, the neurological score, and macrophage infiltration staining with CD68 were increased in middle cerebral artery occlusion (MCAO) mice but significantly reversed by treatment with Trelagliptin. Additionally, Trelagliptin reduced the permeability of the BBB by increasing the expression of the tight junction zonula occludens protein-1 (ZO-1) in the cerebral cortex. In an in vitro hypoxia model of endothelial cells, the increased migration of macrophages, enlarged permeability of endothelial monolayer, downregulation of ZO-1, and elevated expression level of CXCL1 by hypoxic conditions were all reversed by treatment with Trelagliptin in a dose-dependent manner. Our results demonstrate that Trelagliptin might mitigate macrophage infiltration by preventing the breakdown of the blood-brain barrier in the brains of MCAO mice.


Shift length and working practices in UK hospital settings: An online survey of heads of midwifery.
There is currently a lack of data that records how midwives are expected to work in hospital settings. The aim of this study was to determine the prevalence of 12-h shifts and current working practices of hospital-based midwives. An online survey conducted between December 2018 and March 2019. Descriptive data are summarised regionally and nationally. NHS Trusts providing maternity services in hospital settings in the UK PARTICIPANTS: The link to the survey was emailed to Heads of Midwifery in 155 NHS Trusts FINDINGS: Responses were received from 94 of the 155 NHS Trusts (60.65%). Some responses included data for more than one hospital, so results are summarised for 97 hospitals. 12-h shifts were the most prevalent shift length, with only 4.1% of hospitals still routinely operating shorter shifts. 55% of hospitals limit the maximum number of consecutive shifts to three, but this can be influenced by different factors. More than half of midwives (55.67%) will be rostered to start a day shift within 24-h of finishing a night shift. 70% of hospitals do not currently record the number of midwives working beyond their contracted hours but 68% report formal methods of recording missed rest breaks. Regional differences were seen in the use of other personnel to support the midwifery workforce. Shift schedules and the lack of formal methods to record the number of midwives working beyond their contracted hours may be a cause for concern due to the potential impact on recovery times. Further research is required to explore how working practices may affect midwives and their ability to provide care for women and their babies.


The role of prophylactic gastrojejunostomy for unresectable periampullary carcinoma.
One hundred and fifteen patients undergoing palliative bypass for unresectable periampullary carcinoma were reviewed. Postoperative mortality and subsequent length of survival correlated with both presenting symptoms and operative findings. Among 93 patients presenting with biliary obstruction alone, 42 underwent a biliary bypass only and 51, a biliary bypass with a prophylactic gastrojejunostomy. Operative mortality and the postoperative hospital stay were similar for these two groups; postoperative complications tended to be more common in patients undergoing the double bypass. Patients undergoing a biliary bypass alone required significantly more subsequent operations, usually for gastroduodenal obstruction. Thus, it appears that a prophylactic gastrojejunostomy should be performed upon most patients with unresectable periampullary carcinoma presenting with biliary obstruction alone to decrease the number of subsequent palliative operative procedures required.


Elasticities in variable environments: properties and implications.
Elasticities in stochastic matrix models are used to understand both population and evolutionary dynamics. We examine three such elasticities: stochastic elasticity E(ij)(S) with respect to the (i, j) matrix element, the elasticity E(ij)(S mu) with respect to the mean mu(ij) of the matrix element, and the elasticity E(ij)(S sigma) with respect to the variability sigma(ij) of the matrix element. We show that the stochastic elasticity E(S) does not accurately describe the effect of variability; one should use E(S sigma) and E(S mu). We establish two general properties of these elasticities: a sum rule that connects them and a limit on the sum of the E(S sigma). We discuss the implications of these properties for the analysis of buffering and selection on the average rates versus the variability of rates.


Leishmania amazonensis induces modulation of costimulatory and surface marker molecules in human macrophages.
Manipulation of costimulatory and surface molecules that shape the extent of immune responses by Leishmania is suggested as one of the mechanisms of evading the host's defences. The experiments reported here were designed to evaluate the expressions of CD11b, CD11c, CD14, CD18, CD54, CD80, CD86, CD206, MHC class II and TLR-2 (Toll-like receptor 2) in human macrophages infected with L. amazonensis. Phenotypic evaluation revealed a negative modulation in CD11b, CD11c, CD14, CD18, CD54 and MHC class II molecules, depending on the level of infection. The results showed that as early as 1 hour after infection no reduction in marker expression occurs, whereas after 24 hours, downregulation of these molecules was observed in macrophages. No significant changes were observed in the expressions of CD80, CD86, CD206 and TLR2. Evidence of the differential modulation of markers expression and that after parasite uptake no reduction in surface marker expression occurs indicates that parasite internalization is not involved in the phenomena of down-modulation.


A Fatal Hantavirus Pulmonary Syndrome Misdiagnosed as Dengue: An Investigation into the First Reported Case in Rio de Janeiro State, Brazil.
We report the results of an investigation into a fatal case of hantavirus pulmonary syndrome (HPS) in Rio de Janeiro State, Brazil, where the disease had not been reported previous to 2015. Following the notification of an HPS case, serum samples were collected from the household members and work contacts of the HPS patient and tested for antibody to hantaviruses. Seroprevalence of 22% (10/45) was indicated for hantavirus out of 45 human samples tested. Blood and tissue samples were collected from 72 rodents during fieldwork to evaluate the prevalence of hantavirus infection, by using enzyme-linked immunosorbent assay IgG, and to characterize the rodent hantavirus reservoir(s), by reverse transcription polymerase chain reaction and sequencing. Antibody prevalence was 6.9%. The circulation of a single genotype, the Juquitiba hantavirus, carried by two rodent species, black-footed pigmy rice rat (Oligoryzomys nigripes) and cursor grass mouse (Akodon cursor), was shown by analysis of the nucleotide sequences of the S segment. Juquitiba hantavirus circulates in rodents of various species, but mainly in the black-footed pigmy rice rat. HPS is a newly recognized clinical entity in Rio de Janeiro State and should be considered in patients with febrile illness and acute respiratory distress.


Guess What We Can Hear-Novel Voice Biomarkers for the Remote Detection of Disease.
The advancement of digital biomarkers and the provision of remote health care greatly progressed during the coronavirus disease 2019 global pandemic. Combining voice/speech data with artificial intelligence and machine-based learning offers a novel solution to the growing demand for telemedicine. Voice biomarkers, obtained from the extraction of characteristic acoustic and linguistic features, are associated with a variety of diseases and even coronavirus disease 2019. In the current review, we (1) describe the basis on which digital voice biomarkers could facilitate "telemedicine," (2) discuss potential mechanisms that may explain the association between voice biomarkers and disease, (3) offer a novel classification system to conceptualize voice biomarkers depending on different methods for recording and analyzing voice/speech samples, (4) outline evidence revealing an association between voice biomarkers and a number of disease states, and (5) describe the process of developing a voice biomarker from recording, storing voice samples, and extracting acoustic and linguistic features relevant to training and testing deep and machine-based learning algorithms to detect disease. We further explore several important future considerations in this area of research, including the necessity for clinical trials and the importance of safeguarding data and individual privacy. To this end, we searched PubMed and Google Scholar to identify studies evaluating the relationship between voice/speech features and biomarkers and various diseases. Search terms included digital biomarker, telemedicine, voice features, voice biomarker, speech features, speech biomarkers, acoustics, linguistics, cardiovascular disease, neurologic disease, psychiatric disease, and infectious disease. The search was limited to studies published in English in peer-reviewed journals between 1980 and the present. To identify potential studies not captured by our database search strategy, we also searched studies listed in the bibliography of relevant publications and reviews.


Research on the Privacy Security of Face Recognition Technology.
To solve the problem that privacy data are easy to leak in the application of face recognition technology in apps, a method which is based on differential privacy for privacy security protection is proposed. Firstly, Bayesian GAN is conducted to obtain the training data with the same distribution as the privacy data, and the algorithm of differential privacy is conducted to train the training data to obtain these labels with privacy protection. Then, based on the proposed lightface lightweight face recognition model, the tag with noise is generated, and the gradient descent is conducted on the recovered face feature vector from the attack. Finally, through the analysis of privacy loss, an accurate privacy protection boundary is provided. From the results of experiments, it could be known that the proposed privacy security protection method can effectively protect the parameter information of the face recognition model under the face recognition technology and reduce the recognition accuracy of the image recovered by the attacker. Compared with the privacy protection methods such as DPSGD and PATE, it has strong privacy protection ability and can be applied to the privacy protection of practical APP.


[Gender differences in the volume of brain structures in the aspect of physiological aging.]
The aim of the work was to clarify the gender, age and variable differences in the structure of brain structures in healthy volunteers in connection with the task of distinguishing between physiological aging and pathological processes of the brain. The study methods included performing structural MRI of the brain in 131 conditionally healthy volunteers aged 20 to 70 years (72 of them were women and 59 men). Using the method of MR voxel-based morphometry, the total volume of the brain as a whole, as well as its segmented parts, was measured, followed by a comparison of the data obtained in age subgroups and between the sexes. The data obtained in the course of the study indicate that the right and left thalamuses, the left caudate nucleus, the right shell, the left pale ball, and both hippocampus undergo the greatest reduction in size after 60 years. The greatest changes in the hippocampus are the volumes of CA3 Brodman fields. It is established that the process of «physiological aging» of the brain.


A pilot study on the content and the release of Ni and other allergenic metals from cheap earrings available on the Italian market.
The capability of alloys used in cheap jewellery to release metal ions on contact with the skin causing allergic contact dermatitis (ACD) is generally acknowledged. To reduce the diffusion of the Ni-induced ACD the Council Directive 94/27/EC [Council Directive 94/27/EC of 30 June 1994. Official Journal L 188, 22/07/1994, 1.] limited the total Ni content in alloys and its release rate in artificial sweat. In this work, three different aspects were explored: i) the frequency of skin sensitization to Ni-containing earrings in patients before and after the introduction of the Directive's limit; ii) metal composition of alloys by X-ray analysis; iii) metal leaching in artificial sweat followed by Sector Field Inductively Coupled Plasma Mass Spectrometry (SF-ICP-MS) quantification. Well-known allergenic metals, as Ni, Cr and Co, and possible emergent allergens, as Al, Ag, Au, Cd, Cu, Fe, Ir, Mn, Pb, Pd, Pt, Rh, Sn, V and Zn, were studied. Results showed that the frequency of allergy due to earrings did not decrease after the introduction of the Ni limit: in 1994 and in 2005 patients positive to Ni patch tests were 54.3% and 53.5%, respectively. The earring components analyzed were Fe-based or alloys of Cu/Zn or Fe/Cr/Ni, plated with a thin film of precious metal (Ag, Au) which, in several cases, was combined with a Ni layer beneath. Five out of 10 items were not in compliance with the Ni Directive 94/27/EC having a total Ni content >0.05%. In three cases the release of Ni concentrations was higher than the safe sensitizing limit given by the above mentioned Regulation (i.e., <0.5 microg/cm(2)/week). The release of Cu and Zn was very variable among the different pieces (Cu: 0.134-30.9 microg/cm(2)/week; Zn: 0.141-160 microg/cm(2)/week); two objects released high amounts of Fe (358 and 586 microg/cm(2)/week) and one released considerable Mn (21 microg/cm(2)/week). Lead was released from 70% of the objects, while Ag, Al, Cd, Co, Cr and Sn from ca. 30% of the items and concentrations of these elements were well below 0.5 microg/cm(2)/week. Vanadium was released by only one item whereas Au, Ir, Pd, Pt and Rh were never leached.


Mapping and measuring social disparities in premature mortality: the impact of census tract poverty within and across Boston neighborhoods, 1999-2001.
The identification and documentation of health disparities are important functions of public health surveillance. These disparities, typically falling along lines defined by gender, race/ethnicity, and social class, are often made visible in urban settings as geographic disparities in health between neighborhoods. Recognizing that premature mortality is a powerful indicator of disparities in both health status and access to health care that can readily be monitored using routinely available public health surveillance data, we undertook a systematic analysis of spatial variation in premature mortality in Boston (1999-2001) across neighborhoods and sub-neighborhoods in relation to census tract (CT) poverty. Using a multilevel model based framework, we estimated that the incidence of premature mortality was 1.39 times higher (95% credible interval 1.09-1.78) among persons living in the most economically deprived CTs (>/=20% below poverty) compared to those in the least impoverished tracts (<5% below poverty). We present maps of model-based standardized mortality ratios that show substantial within-neighborhood variation in premature mortality and a sizeable decrease in spatial variation after adjustment for CT poverty. Additionally, we present maps of model-based direct standardized rates that can more readily be compared to externally published rates and targets, as well as maps of the population attributable fraction that show that in some of Boston's poorest neighborhoods, the proportion of excess deaths associated with CT poverty reaches 25-30%. We recommend that these methods be incorporated into routine analyses of public health surveillance data to highlight continuing social disparities in premature mortality.


Effects of surgically assisted rapid maxillary expansion on mandibular position: a three-dimensional study.
This study aimed to evaluate three-dimensional changes in mandibular position after surgically assisted rapid maxillary expansion (SARME). A retrospective study was carried out with tomographic records of 30 adult patients with maxillary transverse deficiency who underwent SARME. Cone beam computed tomography scans were obtained preoperatively (T1), after expansion (T2) and 6 months after expansion (T3). Mandibular landmarks were measured with respect to axial, sagittal, and coronal planes. Repeated measures ANOVA was used for statistical analysis. Clockwise rotation and lateral displacement of the mandible were observed immediately after SARME. However, mandibular displacements tended to return close to their initial values at T3. Clockwise rotation and lateral shift of the mandible are transient effects of SARME.


Germacyclobutenes: generation by 1,1-carbalumination or 1,1-carbagallation and their photophysical properties.
Aluminium- and gallium-functionalised alkenylalkynylgermanes, R(1) 2 Ge(C≡C-R(2) )[C{E(CMe3 )2 }=C(H)-R(2) ] (E=Al, Ga), exhibit a close contact between the coordinatively unsaturated Al or Ga atoms and the α-C atoms of the intact ethynyl groups. These interactions activate the Ge-C(alkynyl) bonds and favour the thermally induced insertion of these C atoms into the E-C(vinyl) bonds by means of 1,1-carbalumination or 1,1-carbagallation reactions. For the first time the latter method was shown to be a powerful alternative to known metallation processes. Germacyclobutenes with an unsaturated GeC3 heterocycle and endo- and exocyclic C=C bonds resulted from concomitant Ge-C bond formation to the β-C atoms of the alkynyl groups. These heterocyclic compounds show an interesting photoluminescence behaviour with Stokes shifts of >110 nm. The fascinating properties are based on extended π-delocalisation including σ*-orbitals localised at Ge and Al. High-level quantum chemical DFT and TD-DFT calculations for an Al compound were applied to elucidate their absorption and emission properties. They revealed a biradical excited state with the transfer of a π-electron into the empty p-orbital at Al and a pyramidalisation of the metal atom.


An Overview of Conceptualizations of Eating Disorder Recovery, Recent Findings, and Future Directions.
This review delineates issues in the conceptualization and operationalization of eating disorder recovery, highlights recent findings about recovery (since 2016), and proposes future directions. A longstanding problem in the field is that there are almost as many different definitions of recovery in eating disorders as there are studies on the topic. Yet, there has been a general shift to accepting that psychological/cognitive symptoms are important to recovery in addition to physical and behavioral indices. Further, several operationalizations of recovery have been proposed over the past two decades, and some efforts to validate operationalizations exist. However, this work has had limited impact and uptake, such that the field is suffering from "broken record syndrome," where calls are made for universal definitions time and time again. It is critical that proposed operationalizations be compared empirically to help arrive at a consensus definition and that institutional/organizational support help facilitate this. Themes in recent recovery research include identifying predictors, examining biological/neuropsychological factors, and considering severe and enduring anorexia nervosa. From qualitative research, those who have experienced eating disorders highlight recovery as a journey, as well as factors such as hope, self-acceptance, and benefiting from support from others as integral to the process of recovery. The field urgently needs to implement a universal definition of recovery that is backed by evidence, that can parsimoniously be implemented in clinical practice, and that will lead to greater harmonization of scientific findings.


Quantitative phase imaging of adherent mammalian cells: a comparative study.
The Quantitative phase imaging methods have several advantages when it comes to monitoring cultures of adherent mammalian cells. Because of low photo-toxicity and no need for staining, we can follow cells in a minimally invasive way over a long period of time. The ability to measure the optical path difference in a quantitative manner allows the measurement of the cell dry mass, an important metric for studying the growth kinetics of mammalian cells. Here we present and compare cell measurements obtained with three different techniques: digital holographic microscopy, lens-free microscopy and quadriwave lateral sheering interferometry. We report a linear relationship between optical volume density values measured with these different techniques and estimate the precisions of this measurement for the different individual instruments.


Technology of Two-dimensional Bioimpedance Analysis of the Human Body Composition.
The BIA primary result sheets as a rule contain one-dimensional graphical scales with a selected area of normal values. In 1994, Piccoli et al. proposed BIVA, an alternative form of BIA data presentation, where two bioimpedance parameters are considered simultaneously as tolerance ellipses: resistance and reactance normalized to height. The purpose of this study is to develop an approach to data analysis in body composition bioimpedance research in two-dimensional representations. The data of 1.124.668 patients aged 5 to 85 years who underwent a bioimpedance study in Russian Health Centers from 2009 to 2015 were used. Statistical programming in the R Studio environment was carried out to estimate two-dimensional distribution densities of pairs of body composition parameters for each year of life. The non-Gaussian distribution is found in most parameters of bioimpedance analysis of body composition for most ages (Lilliefors test, p-value << 0.0001). The slices of the actual two-dimensional distribution pairs of body composition parameters had an irregular shape. The authors of the article propose using the actually observed distribution for populations where numerous bioimpedance studies have already been carried out. Such technology can be called two-dimensional bioimpedance analysis of human body composition (2DBIA). The 2DBIA approach is clearer for practitioners and their patients due to the use of body composition parameters in addition to electrical impedance parameters.


Monoclonal antibodies to a Mr 68,000 pore complex glycoprotein interfere with nuclear protein uptake in Xenopus oocytes.
Using a monoclonal antibody (PI1) raised against mouse lymphocyte nuclear matrix fractions we have identified a N-acetylglucosamine (GlcNAc)-containing glycoprotein of Mr 68,000 as a component of the nuclear pore complexes of Xenopus laevis oocytes. The antigenic determinant recognized by antibody PI1 comprises both the sugar moiety and protein sequences since, on the one hand, added GlcNAc competed effectively for antibody binding and, on the other hand, the antibody reacted in immunoblots with only one member of the GlcNAc-containing pore complex glycoprotein family. By using immunogold-electron microscopy we could demonstrate that the Mr 68,000 glycoprotein was located preferentially to the cytoplasmic side of the pore complex channel. When radiolabeled soluble nuclear proteins were injected into the cytoplasm of Xenopus oocytes, their reentry into the nucleus was almost completely inhibited in the presence of antibody PI1 as shown by two-dimensional gel electrophoresis. The results indicate that the evolutionarily conserved Mr 68,000 glycoprotein is involved in transport processes of karyophilic proteins from the cytoplasm into the nucleus.