Psychological therapies for the prevention of migraine in adults.
Migraine is a common neurological problem associated with the highest burden amongst neurological conditions in terms of years lived with disability. Medications can be used as prophylaxis or rescue medicines, but are costly and not always effective. A range of psychological interventions have been developed to manage migraine. The objective was to evaluate the efficacy and adverse events of psychological therapies for the prevention of migraine in adults. We searched CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL from their inception until July 2018, and trials registries in the UK, USA, Australia and New Zealand for randomised controlled trials of any psychological intervention for adults with migraine. We included randomised controlled trials (RCTs) of a psychological therapy for people with chronic or episodic migraine, with or without aura. Interventions could be compared to another active treatment (psychological or medical), an attention-placebo (e.g. supportive counselling) or other placebo, routine care, or waiting-list control. We excluded studies where fewer than 15 participants completed each arm. We extracted study characteristics and outcome data at post-treatment and the longest available follow-up. We analysed intervention versus control comparisons for the primary outcome of migraine frequency. We measured migraine frequency using days with migraines or number of migraine attacks measured in the four weeks after treatment. In addition, we analysed the following secondary outcomes: responder rate (the proportion of participants with a 50% reduction in migraine frequency between the four weeks prior to and the four weeks after treatment); migraine intensity; migraine duration; migraine medication usage; mood; quality of life; migraine-related disability; and proportion of participants reporting adverse events during the treatment. We included these variables, where available, at follow-up, the timing of which varied between the studies. We used the GRADE approach to judge the quality of the evidence. We found 21 RCTs including 2482 participants with migraine, and we extracted meta-analytic data from 14 of these studies. The majority of studies recruited participants through advertisements, included participants with migraine according to the International Classification of Headache Disorders (ICHD) criteria and those with and without aura. Most intervention arms were a form of behavioural or cognitive-behavioural therapy. The majority of comparator arms were no treatment, routine care or waiting list. Interventions varied from one 20-minute session to 14 hours of intervention. No study had unequivocally low risk of bias; all had at least one domain at high risk of bias, and 20 had two to five domains at high risk. Reporting of randomisation procedures and allocation concealment were at high or unclear risk of bias. We downgraded the quality of evidence for outcomes to very low, due to very serious limitations in study quality and imprecision. Reporting in trials was poor; we found no preregistrations stipulating the outcomes, or demonstrating equivalent expectations between groups. Few studies reported our outcomes of interest, most only reported outcomes post treatment; follow-up data were sparse.Post-treatment effectsWe found no evidence of an effect of psychological interventions for migraine frequency in number of migraines or days with migraine (standardised mean difference (SMD) -0.02, 95% confidence interval (CI) -0.17 to 0.13; 4 studies, 681 participants; very low-quality evidence).The responder rate (proportion of participants with migraine frequency reduction of more than 50%) was greater for those who received a psychological intervention compared to control: 101/186 participants (54%) with psychological therapy; 37/152 participants (24%) with control (risk ratio (RR) 2.21, 95% CI 1.63 to 2.98; 4 studies, 338 participants; very low-quality evidence). We found no effect of psychological therapies on migraine intensity (SMD -0.13, 95% CI -0.28 to 0.02; 4 studies, 685 participants). There were no data for migraine duration (hours of migraine per day). There was no effect on migraine medication usage (SMD -0.06, 95% CI -0.35 to 0.24; 2 studies, 483 participants), mood (mean difference (MD) 0.08, 95% CI -0.33 to 0.49; 4 studies, 432 participants), quality of life (SMD -0.02, 95% CI -0.30 to 0.26; 4 studies, 565 participants), or migraine-related disability (SMD -0.67, 95% CI -1.34 to 0.00; 6 studies, 952 participants). The proportion of participants reporting adverse events did not differ between those receiving psychological treatment (9/107; 8%) and control (30/101; 30%) (RR 0.16, 95% CI 0.00 to 7.85; 2 studies, 208 participants). Only two studies reported adverse events and so we were unable to draw any conclusions.We rated evidence from all studies as very low quality.Follow-upOnly four studies reported any follow-up data. Follow-ups ranged from four months following intervention to 11 months following intervention. There was no evidence of an effect on any outcomes at follow-up (very low-quality evidence). This review identified 21 studies of psychological interventions for the management of migraine. We did not find evidence that psychological interventions affected migraine frequency, a result based on four studies of primarily brief treatments. Those who received psychological interventions were twice as likely to be classified as responders in the short term, but this was based on very low-quality evidence and there was no evidence of an effect of psychological intervention compared to control at follow-up. There was no evidence of an effect of psychological interventions on medication usage, mood, migraine-related disability or quality of life. There was no evidence of an effect of psychological interventions on migraine frequency in the short-term or long-term. In terms of adverse events, we were unable to draw conclusions as there was insufficient evidence. High and unclear risk of bias in study design and reporting, small numbers of participants, performance and detection bias meant that we rated all evidence as very low quality. Therefore, we conclude that there is an absence of high-quality evidence to determine whether psychological interventions are effective in managing migraine in adults and we are uncertain whether there is any difference between psychological therapies and controls.


Osteoporotic fractures and hospitalization risk in chronic spinal cord injury.
Osteoporosis is a well acknowledged complication of spinal cord injury. We report that motor complete spinal cord injury and post-injury alcohol consumption are risk factors for hospitalization for fracture treatment. The clinical assessment did not include osteoporosis diagnosis and treatment considerations, indicating a need for improved clinical protocols. Treatment of osteoporotic long bone fractures often results in lengthy hospitalizations for individuals with spinal cord injury. Clinical features and factors that contribute to hospitalization risk have not previously been described. Three hundred and fifteen veterans > or = 1 year after spinal cord injury completed a health questionnaire and underwent clinical exam at study entry. Multivariate Cox regression accounting for repeated events was used to assess longitudinal predictors of fracture-related hospitalizations in Veterans Affairs Medical Centers 1996-2003. One thousand four hundred and eighty-seven hospital admissions occurred among 315 participants, and 39 hospitalizations (2.6%) were for fracture treatment. Median length of stay was 35 days. Fracture-related complications occurred in 53%. Independent risk factors for admission were motor complete versus motor incomplete spinal cord injury (hazard ratio = 3.73, 95% CI = 1.46-10.50). There was a significant linear trend in risk with greater alcohol consumption after injury. Record review indicated that evaluation for osteoporosis was not obtained during these admissions. Assessed prospectively, hospitalization in Veterans Affairs Medical Centers for low-impact fractures is more common in motor complete spinal cord injury and is associated with greater alcohol use after injury. Osteoporosis diagnosis and treatment considerations were not part of a clinical assessment, indicating the need for improved protocols that might prevent low-impact fractures and related admissions.


Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on ubiquinone levels in rat skeletal muscle and heart: relationship to cytotoxicity and inhibitory activity for cholesterol synthesis in human skeletal muscle cells.
Although statins are prescribed as relatively safe and effective drugs for hypercholesterolemic patients, it has been reported that a significant side effect, myopathy, occurs infrequently during medication. Moreover, because statins decrease cardiac ubiquinone levels, the risk of cardiac dysfunction has been suggested. This study sought to evaluate and compare the cytotoxicity of statins (cerivastatin, pitavastatin, fluvastatin, simvastatin, atorvastatin and pravastatin) in cultured human skeletal muscle cells (HSkMCs) and the effects on ubiquinone levels in statin-treated rat skeletal muscle and heart. Cerivastatin, the most potent inhibitor of HMG-CoA reductase, showed the strongest cytotoxicity (over 10-fold) among the statins examined, while the effects of the others were in a similar range. In rat experiments, neither pitavastatin nor cerivastatin decreased ubiquinone levels in skeletal muscle, but both dose-dependently lowered ubiquinone levels in the heart. As the rates of reduction by pitavastatin (9.6% at 30 mg/kg) and cerivastatin (9.7% at 0.3 mg/kg) were almost equal, it was estimated that cerivastatin reduced ubiquinone levels in the rat heart approximately 100-fold more strongly than pitavastatin, based on the effective doses. We found that cerivastatin showed the most potent cytotoxicity in HSkMCs and strongly lowered ubiquinone levels in the rat heart.


Defect Passivation in Lead-Halide Perovskite Nanocrystals and Thin Films: Toward Efficient LEDs and Solar Cells.
Lead-halide perovskites (LHPs), in the form of both colloidal nanocrystals (NCs) and thin films, have emerged over the past decade as leading candidates for next-generation, efficient light-emitting diodes (LEDs) and solar cells. Owing to their high photoluminescence quantum yields (PLQYs), LHPs efficiently convert injected charge carriers into light and vice versa. However, despite the defect-tolerance of LHPs, defects at the surface of colloidal NCs and grain boundaries in thin films play a critical role in charge-carrier transport and nonradiative recombination, which lowers the PLQYs, device efficiency, and stability. Therefore, understanding the defects that play a key role in limiting performance, and developing effective passivation routes are critical for achieving advances in performance. This Review presents the current understanding of defects in halide perovskites and their influence on the optical and charge-carrier transport properties. Passivation strategies toward improving the efficiencies of perovskite-based LEDs and solar cells are also discussed.


Intravenous Zoledronic Acid 5 mg on Bone Turnover Markers and Bone Mineral Density in East China Subjects with Newly Diagnosed Osteoporosis: A 24-month Clinical Study.
This randomized, double-blind, placebo-controlled study assessed the necessity of early intervention, safety and efficacy of intravenous zoledronic acid 5 mg/year in East China women with newly diagnosed osteoporosis at high risk of fracture during a 24-month treatment period. Subjects (57 [52-62] years old) were randomized 3:2 to zoledronic acid versus placebo (randomized at baseline, zoledronic acid [175 cases], placebo-zoledronic acid [110 cases]). The bone mineral density of the lumbar spine and total hip was measured every 6 months with the use of dual-energy X-ray absorptiometry. Serum procollagen I N-terminal pro-peptide (PINP) and serum C-telopeptide of type I collagen (CTX) levels were measured every 6 months. The primary end point was the rate of change in the bone mineral density at the posteroanterior spine. For subjects with measurements at 24 months, zoledronic acid significantly increased bone mineral density (BMD) at the lumbar spine (mean percent change ± SD, zoledronic acid 5.390% ± 0.854% versus placebo-zoledronic acid -1.038% ± 0.599%), the total hip (zoledronic acid 1.900% ± 0.262% versus placebo-zoledronic acid -1.631% ± 0.649%). Serum procollagen I N-terminal pro-peptide (PINP) and CTX decreased rapidly with zoledronic acid 5 mg treatment (P < 0.001 versus placebo at 6 month and 24 months) and changed from baseline in the zoledronic acid 5 mg and placebo-zoledronic acid 5 mg at 6 months by a mean of -66.348% and -75.375%, respectively (P < 0.001), and at 24 months by -49.950% and -52.325%, respectively (P < 0.001). No cases of serious adverse events were observed in two groups. Headache, pyrexia and myalgia occurred more commonly within the first 3 days after infusion with zoledronic acid 5 mg than with placebo (13.7% versus 2.1%, P = 0.0018; 28.0% versus 3.2%, P < 0.001; 21.7% versus 4.2%, P < 0.001, respectively). These data show that early application of zoledronic acid 5 mg/year was well stimulated and tolerated for bone mass in newly diagnosed east china subjects with osteoporosis in a 24-month treatment.


Elevated vascular angiotensin converting enzyme in chronic two-kidney, one clip hypertension in the dog.
The possible role of the vascular angiotensin converting enzyme (ACE) in the development of two-kidney, one clip (2-K, 1C) hypertensive dogs was studied in different blood vessels. Vascular ACE activity per mg protein differed in a variety of blood vessels; the activity appeared to vary inversely with the outer diameter of arteries. The systemic blood pressure in mongrel dogs increased after partial occlusion of the left renal artery, and the hypertension lasted for 8 months. Plasma renin activity (PRA) was raised only for the first 4 weeks after the operation and then returned to the original level in the chronic stage of hypertension. Plasma ACE activity did not alter during the experimental period. In contrast, ACE activities in the jejunal, pulmonary and renal arteries, aorta, lung and cerebral cortex, significantly increased in the chronic hypertensive stage (8 months after occlusion). The production of angiotensin II (ANG II) from ANG I was significantly greater in isolated arteries from 8-month hypertensive dogs than in those from normotensive dogs when assessed by the contractile responses to ANG I and ANG II. These results indicate that acceleration by increased vascular ACE activity of the production of ANG II in the vascular wall may contribute to the maintenance of hypertension in the chronic stage of 2-K, 1C hypertensive dogs having normal PRA and plasma ACE activity.


Temporal Profile of MicroRNA Expression in Contused Cortex after Traumatic Brain Injury in Mice.
MicroRNAs (miRNAs) were recently identified as important regulators of gene expression under a wide range of physiological and pathophysiological conditions. Thus, they may represent a novel class of molecular targets for the management of traumatic brain injury (TBI). In this study, we investigated the temporal profile of miRNA expression during the development of secondary brain damage after experimental TBI. For this purpose, we used a controlled cortical impact model in C57Bl/6 mice (n = 6) to induce a cortical contusion and analyzed miRNA expression in the traumatized cortex by microarray analysis during the development of secondary contusion expansion-i.e., at 1, 6, and 12 h after TBI. Of a total 780 mature miRNA sequences analyzed, 410 were detected in all experimental groups. Of these, 158 miRNAs were significantly upregulated or downregulated in TBI compared with sham-operated animals, and 52 miRNAs increased more than twofold. We validated the upregulation of five of the most differentially expressed miRNAs (miR-21*, miR-144, miR-184, miR-451, miR-2137) and the downregulation of four of the most differentially expressed miRNAs (miR-107, miR-137, miR-190, miR-541) by quantitative polymerase chain reaction (qPCR). miR-2137, the most differentially expressed miRNA after TBI, was further investigated by in situ hybridization and was found to be upregulated in neurons within the traumatic penumbra. This study gives a comprehensive picture of miRNA expression levels during secondary contusion expansion after TBI and may pave the way for the identification of novel targets for the management of brain trauma.


Procollagen intermediates during tendon fibrillogenesis.
The purpose of this study was to correlate ultrastructural features of tendon collagen fibrils at various stages of development with the presence of procollagen, pN-collagen, pC-collagen, and the free amino propeptides and carboxyl propeptide of type I procollagen. Tendons from 10-, 14-, and 18-day chicken embryos reveal small, well-defined intercellular compartments containing collagen fibrils with diameters showing a unimodal distribution. At 21 days (hatching) and 9 days (post hatching) and at 5 weeks (post hatching), the compartments are larger, less well-defined, and there is multimodal distribution of tendon fibril diameters. Procollagen and the intermediates pN-collagen and pC-collagen are present in tendons up to 18 days. Thereafter there is a marked reduction in procollagen, whereas the intermediates persist throughout all stages of development. Similarly, free amino propeptides and carboxyl propeptides of type I procollagen were found at all stages. The amino propeptide of type III procollagen was restricted to the peritendineum until 7 weeks post hatching. At that time, a network of fibrils containing the amino propeptide of type III procollagen was seen delineating well-circumscribed compartments of collagen fibrils throughout the entire tendon. This study supports the notion that pN- and pC-collagen have an extracellular role and participate in collagen fibrillogenesis.


Is Surgical Navigation Useful for Treating Zygomatic Arch Fractures?
To report the case of a 58-year-old man with a zygomatic arch fracture, which was well localized and reduced using a surgical navigation system. In this clinical report, the authors suggest intraoperative surgical navigation systems are useful diagnostically and for localizing sites of zygomatic arch fractures. The patient underwent successful closed reduction of zygomatic arch fractures using a surgical navigation system. Surgical navigation is a useful tool for identifying the locations of zygomatic arch fractures and for guiding closed reduction. Surgical navigation is recommended for localizing the sites of zygomatic fractures.


Transient Competitive Inhibition Bypasses the Binding Site Barrier to Improve Tumor Penetration of Trastuzumab and Enhance T-DM1 Efficacy.
Poor penetration of mAbs in solid tumors is explained, in part, by the binding site barrier hypothesis. Following extravasation, mAbs rapidly bind cellular antigens, leading to the observation that, at subsaturating doses, therapeutic antibody in solid tumors localizes around tumor vasculature. Here we report a unique strategy to overcome the binding site barrier through transient competitive inhibition of antibody-antigen binding. The anti-trastuzumab single domain antibody 1HE was identified through in vitro binding assays as a model inhibitor. Coadministration of 1HE did not alter the plasma pharmacokinetics of trastuzumab or ado-trastuzumab emtansine (T-DM1) in vivo. Administration of 1HE alone was rapidly eliminated with a terminal plasma half-life of 1.2 hours, while coadministrations of 1HE with trastuzumab had a terminal half-life of 56 hours. In mice harboring SKOV3 xenografts, coadministration of 1HE with trastuzumab led to significant increases in both penetration of trastuzumab from vasculature and the percentage of tumor area that stained positive for trastuzumab. 1HE coadministered with a single dose of T-DM1 to NCI-N87 xenograft-bearing mice significantly enhanced T-DM1 efficacy, increasing median survival. These results support the hypothesis that transient competitive inhibition can improve therapeutic antibody distribution in solid tumors and enhance antibody efficacy. SIGNIFICANCE: This study describes the development of a transient competitive inhibition strategy that enhances the tumor penetration and efficacy of anticancer antibodies.See related commentary by van Dongen, p. 3956.


[Effect of metals, benzene, pesticides and ethylene oxide on the haematopoietic system].
The hematopoietic system, due to intensive cells proliferation, is very sensitive to toxic substances. Many chemicals, including benzene, pesticides (dithiocarbamines), ethylene oxide and metals (mercury, cadmium, chrome, cobalt, lead, aluminum) exert their toxic effect on the hematopoietic system. Exposure to each of these substances may occur in the work place due to environmental pollution and in municipal or residential areas. Exposure to lead, aluminum, cadmium, and benzene results in the incidence of anemia. In addition, exposure to benzene and its metabolites leads to myelodysplastic syndromes, leukemia, lymphomas and bone marrow aplasia. Ethylene oxide induces neoplasm of the hematopoietic system and lymphomas, especially non-Hodgkin lymphoma. Arsenic compounds act like immunosuppressants. Mercury and chrome affect the immune system by immunosuppression and by evoking autoimmune reactions. Dithiocarbamates are suspected to induce leukemia. An analysis of the pathophysiology of individual substances reveal universal toxic mechanisms. In this paper, the authors discuss the pathomechanism of toxic effects of the aforesaid chemicals on the haematopoietic system and peripheral blood cells from the viewpoint of mutagenesis, apoptosis, myelotoxicity, anemia, immunomodulation, and individual sensitivity.


LIMITED DISPERSAL AND PROXIMITY-DEPENDENT MATING SUCCESS IN THE COLONIAL ASCIDIAN BOTRYLLUS SCHLOSSERI.
Although the propagules of many sessile organisms have the capacity to disperse over large distances, dispersal is often spatially restricted. In this paper, I document, using a combination of mark/recapture techniques and histocompatibility assays, dispersal distance of the planktonic larvae of the sessile, colonial sea squirt Botryllus schlosseri. Both of these methods indicate that most larvae remain within a meter of their birthplace. Such limited dispersal should lead to increased matings among relatives, and the potential for inbreeding depression. However, the success of: 1) fertilization, 2) embryogenesis, and 3) larval metamorphosis all decrease as distance between mated colonies increases. The spatial scale over which this decrease in mating success occurs is concordant with the estimates of dispersal distance based on the larval mark/recapture data and histocompatibility assays. Taken together, these results imply that inbreeding depression is not a necessary consequence of limited dispersal and consanguineous matings in B. schlosseri.


Cytoprotective effect of propolis on heat stress induces alteration to histological, ultrastructural, and oxidative stress in catfish (Clarias gariepinus).
Our study helps to evaluate the immune response, antioxidative status, and resistance against heat stress (HS) in Clarias gariepinus treated with propolis extraction; the results will contribute to theories of fish physiology and immunity under high-temperature conditions. Forty-five fish were divided into three equal groups: the control, the HS group at 36 °C, and the HS treated with alcoholic extraction of propolis that dissolved in water for 3 weeks. The results of our study suggested that the stress response differs among tissues thymus, spleen, and liver. All the tissues showed alteration in morphological and cytological structure at the light microscope (LM) and transmission electron microscope (TEM); thymus showed edema and thymocyte destruction; the spleen detected collagen deposition, and the liver displayed endoplasmic reticulum amplification (ER). In addition, we examined oxidative stress and antioxidant defenses (lipid peroxidation, catalase, and glutathione) of the spleen and measured blood biochemical parameters (alanine transaminase and aspartic transaminase levels) after heat stress. However, this toxic effect of HS was neutralized by the propolis extraction. To conclude, propolis is recommended to cope with the impacts of heat stress on catfish (Clarias gariepinus) by improving immunity and antioxidative resistance.


The complete chloroplast genome of Desmodium styracifolium.
The complete chloroplast genome (cpDNA) of Desmodium styracifolium, an important medicinal herb for urolithiasis treatment, was sequenced and assembled from the whole genome data. The cpDNA of D. styracifolium is 149,155 bp in length with GC content of 35.2%. The genome has a quadripartite structure that is composed of a large single-copy (LCS, 82,476 bp) and small single-copy (SSC, 18,439 bp) separated by a pair of inverted repeats (IRa and IRb, 24,120 bp each). There are 128 genes in the chloroplast genome, including 83 protein-coding genes, 8 rRNA genes and 37 tRNA genes.


Prevalence of skin lesions in turkeys at slaughter.
1. The aims of this study were (i) to evaluate the prevalence of welfare-related cutaneous lesions in turkeys at the end of the rearing period and (ii) to study the correlations between lesions. 2. The percentage of lesions in each flock was determined by observation at the slaughterhouse. Sixty flocks were investigated in 13 slaughterhouses between April and July 2006. 3. All flocks showed a high proportion of turkeys with footpad lesions, with 40·7% of turkey flocks having severe footpad dermatitis. A significant number of feet had swelling of the footpad and deviated toes (60·0% and 21·4% respectively). Arthritis was observed in 25·4% of the carcases and an average of 30·1% had breast buttons on the keel. 4. Positive correlations were found between evidence of feather pecking and arthritis, toe deviations and swelling of the footpad. Deviated toes, swelling of the feet and feather pecking were negatively linked to the most severe scratches (P < 0·001). 5. A method is proposed to assess turkey welfare at the slaughterhouse based on several criteria: footpad lesions, arthritis, severe scratches, deviated toes, swelling of the footpad and breast buttons.


Novel Multitarget-Directed Ligands Aiming at Symptoms and Causes of Alzheimer's Disease.
Alzheimer's disease (AD) is a major public health problem, which is due to its increasing prevalence and lack of effective therapy or diagnostics. The complexity of the AD pathomechanism requires complex treatment, e.g. multifunctional ligands targeting both the causes and symptoms of the disease. Here, we present new multitarget-directed ligands combining pharmacophore fragments that provide a blockade of serotonin 5-HT6 receptors, acetyl/butyrylcholinesterase inhibition, and amyloid β antiaggregation activity. Compound 12 has displayed balanced activity as an antagonist of 5-HT6 receptors ( Ki = 18 nM) and noncompetitive inhibitor of cholinesterases (IC50 hAChE = 14 nM, IC50 eqBuChE = 22 nM). In further in vitro studies, compound 12 has shown amyloid β antiaggregation activity (IC50 = 1.27 μM) and ability to permeate through the blood-brain barrier. The presented findings may provide an excellent starting point for further studies and facilitate efforts to develop new effective anti-AD therapy.


Emerging Piglet Models of Neonatal Short Bowel Syndrome.
Short bowel syndrome (SBS) is a growing problem in the human neonatal population. In infants, SBS is the leading cause of intestinal failure, the state of being unable to absorb sufficient nutrients for growth and development. Neonates with SBS are dependent on long-term parenteral nutrition therapy, but many succumb to the complications of sepsis and liver disease. Research in neonatal SBS is challenged by the ethical limits of studying sick human neonates and the heterogeneous nature of the disease process. Outcomes in SBS vary depending on residual intestinal anatomy, intestinal length, patient age, and exposure to nutrition therapies. The neonatal piglet serves as an appropriate translational model of the human neonate because of similarities in gastrointestinal ontogeny, physiological maturity, and adaptive processes. Re-creating the disease process in a piglet model presents a unique opportunity for researchers to discover novel insights and therapies in SBS. Emerging piglet models of neonatal SBS now represent the entire spectrum of disease seen in human infants. This review aims to contextualize these emerging piglet models within the context of SBS as a heterogeneous disease. We first explore the factors that account for SBS heterogeneity and then explore the suitability of the neonatal piglet as an appropriate translational animal model. We then examine differences between the emerging piglet models of neonatal SBS and how these differences affect their translational potential to human neonates with SBS.


Disassembly and domain structure of the proteins in the signal-recognition particle.
The signal-recognition particle (SRP) is a ribonucleoprotein (RNP) complex consisting of six different polypeptide chains and a 7SL RNA. It participates in initiating the translocation of proteins across the membrane of the endoplasmic reticulum. SRP was disassembled in 2 M KCl into three components, one RNP composed of 7SL RNA and the 54-kDa and 19-kDa proteins, and two heterodimers consisting of the 72/68-kDa and the 14/9-kDa proteins respectively. The 54-kDa protein could be released from the RNP subparticle by chromatography on DEAE-Sepharose in Mg2+-depleted buffer, while the 19-kDa protein remained bound to the 7SL RNA. The domain structure of SRP proteins was probed by using mild elastase treatment and protein-specific antibodies. It was found that the 72, 68, 54 and 19-kDa SRP proteins were proteolytically processed in distinct steps. Most remarkably a protein fragment of 55-kDa, generated from the 72-kDa SRP protein, and a 35-kDa fragment from the 54-kDa SRP protein were both released from the RNP particle. Fragments generated from the 68-kDa protein and detectable with the anti-(68-kDa protein) antibody remained associated with the RNP particle. Cleavage of the SRP proteins by elastase at 2.5 micrograms/ml resulted in partial loss of activity, while 10 micrograms/ml caused complete inactivation of the particle. Neither the elongation arrest of IgG light chain nor its translocation across SRP-depleted microsomal membranes was promoted. The implications of these results on the possible interaction between the SRP subunits are discussed.


A novel polyaniline/polypyrrole/graphene oxide fiber for the determination of volatile organic compounds in headspace gas of lung cell lines.
Exploration of volatile organic compounds (VOCs) generated by lung cell lines is a powerful and non-invasive tool for the detection of potential volatile biomarkers of lung cancer. In this study, a simple and sensitive solid phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) method was developed for the determination of VOCs in the headspace gas of lung cell lines. For the purpose of preconcentration, a novel polyaniline/polypyrrole/graphene oxide (PANI/PPy/GO) coating was prepared on the surface of stainless steel fiber via in-situ electrochemical deposition for the first time. The characteristic properties of the coating were studied and the results revealed that the coating possessed large surface area, high extraction efficiency, excellent thermal and mechanical stability as well as long lifespan. Some parameters affecting the extraction efficiency such as synthesis conditions, extraction and desorption conditions were optimized. Under the optimal conditions, the method displayed relatively wide linear range (three or four orders of magnitude) with correlation coefficients above 0.9916. Low detection limits from 1.0 to 12ngL-1 were obtained. Relative standard deviations ranged from 1.2% to 18.0% indicating good repeatability and reproducibility of the method. This method has been successfully applied to analyze VOCs in the headspace gas of lung adenocarcinoma epithelial cell line (A549) and human embryonic fibroblast cell line (MRC-5).


Molecular characterisation of 'transmembrane protein 192' (TMEM192), a novel protein of the lysosomal membrane.
Transmembrane protein 192 (TMEM192) has been previously identified in proteomic analyses of lysosomal membranes. TMEM192 does not exhibit any significant homology to known protein families and possesses four potential transmembrane segments. To approach the molecular role of TMEM192, a detailed biochemical characterisation of this protein was performed. Expression constructs of fusion proteins containing TMEM192 and appended epitope tags were constructed. In HeLa cells these proteins were detected in membranes of lysosomes/late endosomes. To examine endogenous TMEM192, a TMEM192-specific antibody was generated and validated. With this antibody colocalisation of endogenous TMEM192 with lysosomal and late endosomal markers was demonstrated. Using Percoll density gradient centrifugation and immunoblotting, co-sedimentation of major portions of both TMEM192 and the lysosomal proteins LAMP-2 and cathepsin D into high-density fractions was observed. Interestingly, in contrast to many other lysosomal proteins no N-glycosylation of TMEM192 could be detected. Western blotting of reduced and non-reduced samples and co-immunoprecipitation experiments indicated TMEM192 to be a homodimer with one or more interchain disulphide bridges. TMEM192 was found to be strongly expressed in human kidney, liver, lung and pancreas tissue. The widespread tissue distribution could suggest an important role of TMEM192 for lysosomal function.


Feature extraction algorithm of a precession target based on a Doppler frequency profile of dual-aspect observation.
In ballistic missile defense, using precession parameters is an effective way to determine warheads from decoys. Due to the geometric theory of diffraction, the backscattered field from a smooth object for a microwave radar consists of contributions from only isolated scattering centers. Further, thanks to the short wavelength of the laser, the ladar could obtain complete Doppler information of illuminated parts of precessing targets. On the basis of modeling the observation geometry of a rotating target with precession, a novel method for extracting precession parameters using coherent ladar based on a Doppler frequency profile (DFP) of dual-view observation is first proposed, to the best of our knowledge. By analyzing the periodic changes of bandwidth of a cone-shaped precessing object, we indicate that the sequence of DFP bandwidth can be approximate to a sinusoid function, based on which the precession period can be obtained through sinusoidal fitting. The precession angle can be obtained by combining dual-aspect receiving observation. A laboratory experiment verified the effectiveness of the proposed algorithm, and the errors of extracted parameters are about 10%.


Human leukocyte antigen class II haplotypes that protect against or predispose to streptococcal toxic shock.
In the United States, 1.5-5.2/100,000 persons develop invasive Streptococcus pyogenes infections each year, and approximately 10%-20% of these patients go on to develop streptococcal toxic shock syndrome (STSS). Patients who develop STSS usually present with generalized erythema, conjunctivitis, and confusion. Fulminant cardiovascular shock develops over a period of a few hours, accompanied by multiorgan failure. Between 20% and 40% of patients with STSS die, compared with approximately 10% of patients with invasive streptococcal disease without STSS.


Atorvastatin treatment improves diabetic polyneuropathy electrophysiological changes in non-insulin dependent diabetic patients: a double blind, randomized clinical trial.
Statins are widely used amongst diabetic patients. Recently, it has been proposed that they may exert many beneficial effects on vascular function regardless of their cholesterol lowering action. There are also growing concerns about statins-induced polyneuropathy in diabetic patients. As far as we know, this is the first clinical trial that has studied the effect of atorvastatin on electrophysiological parameters in diabetic neuropathy. This was a randomized, double-blind, placebo-controlled clinical trial that assessed nerve conduction velocity (NCV) parameters after a six-month therapy with atorvastatin, 20 mg per day. Although there was an 11% difference in Motor to F-wave conduction velocity ratio (M/F ratio) between the studied group and the controls, this difference was not statistically significant. Motor conduction velocity (MCV) significantly improved by 5% (P<0.05) and the F wave was not significantly deteriorated. In conclusion, treatment with statins may have a beneficial effect on diabetic neuropathy electrophysiological changes, at least in the short-term.


Clinical examination of the shoulder complex.
A comprehensive and systematic approach to physical examination of the shoulder is described, with particular emphasis on findings pertinent to an athletic population. The format consists of initial impression, inspection, palpation, range of motion and strength testing, stability assessment, special tests, vascular examination, and general physical examination.


Leiomyosarcoma of the splenic vein: A case report.
Leiomyosarcomas (LMSs) originating from the wall of blood vessels are aggressive and rare neoplasms. The current study describes a case of a 52-year-old man who presented with intermittent abdominal pain without weight loss or diarrhea. Computed tomography of the abdomen identified a 4-cm, solid, heterogeneous tumor in the tail of the pancreas, while a hypodense lesion was also noted in the right hepatic lobe. The patient subsequently underwent splenic pedicle tumor resection, splenectomy and liver tumor resection. Notably, immunohistochemical and histological analyses identified LMS, which had originated from the smooth muscle of the splenic vein. Currently available information regarding LMSs of the splenic vein and their management is also discussed, with the aim of improving diagnostic accuracy.


Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients.
Placental growth factor (PlGF), a VEGF-homolog implicated in tumor angiogenesis and adaptation to antiangiogenic therapy, is emerging as candidate target in malignancies. Here, we addressed the expression, function, and prognostic value of PlGF in neuroendocrine tumors (NETs). PlGF was determined in NET patients' sera collected retrospectively (n=88) and prospectively (n=87) using Roche-Elecsys and correlated with clinicopathological data. Tumoral PlGF was evaluated by immunohistochemistry, effects of PlGF on proliferation and migration in vitro were assessed using different NET cell lines and effects on tumor growth in vivo in orthotopic xenografts. Circulating and tumoral PlGF was elevated in patients with pancreatic NETs (pNETs) compared with control sera and respective healthy tissue. De novo PlGF expression occurred primarily in the tumor stroma, suggesting paracrine stimulatory circuits. Indeed, PlGF enhanced NET proliferation and migration in vitro and, conversely, neutralizing antibodies to PlGF reduced tumor growth in vivo. Elevated circulating PlGF levels in NET patients correlated with advanced tumor grading and were associated with reduced tumor-related survival in pNETs. Subsequent determinations confirmed and extended our observation of elevated PlGF levels in a prospective cohort of grade 1 and grade 2 pNETs (n=30) and intestinal NETs (n=57). In low-grade pNETs, normal circulating PlGF levels were associated with better survival. In intestinal NETs, circulating PlGF above median emerged as an independent prognostic factor for shorter time-to-progression in multivariate analyses. These data assign to PlGF a novel function in the pathobiology of NETs and propose PlGF as a prognostic parameter and therapeutic target.


Integrating Drug's Mode of Action into Quantitative Structure-Activity Relationships for Improved Prediction of Drug-Induced Liver Injury.
Drug-induced liver injury (DILI) is complex in mechanism. Different drugs could undergo different mechanisms but result in the same DILI type, while the same drug could lead to different DILI types via different mechanisms. Therefore, predicting a drug's potential for DILI should take its underlying mechanisms into consideration. To achieve that, we constructed a novel approach by incorporating the drug's Mode of Action (MOA) into Quantitative Structure-Activity Relationship (QSAR) modeling. This MOA-DILI approach was examined using a data set of 333 drugs. The drugs were first grouped according to their MOA profiles (positive or negative in each MOA) based on the Tox21 qHTS assays. QSAR models for individual MOA assays were developed and subsequently combined to obtain the MOA-DILI model. A hold-out testing strategy (222 drugs for training and 111 drugs as a test set) was employed, which yielded a predictive accuracy of 0.711. The MOA-DILI model was directly compared with the standard QSAR approach using the same hold-out strategy, and the QSAR model yielded an accuracy of 0.662. To minimize the random chance in splitting training/test sets, the hold-out testing process was repeated 1000 times, and the observed difference in prediction accuracy between MOA-DILI and QSARs was statistically significant (P value <0.0001). Out of 17 MOAs used, four assays (i.e., antioxidant response elements, PPAR-gamma, estrogen receptor, and thyroid receptor assays) contributed most to the improved prediction of the MOA-DILI model over QSARs. In conclusion, the MOA-DILI approach has the potential to significantly improve predictive outcomes and to reveal complex relationships between MOAs and DILI, all of which would be helpful in developing DILI predictive models in drug screening and for risk assessment of industrial chemicals.


The influence of temporal stimulus changes on speech-evoked potentials revealed by approximations of tone-evoked waveforms.
The aim of the study was to determine whether cortical auditory potentials evoked by monosyllabic words beginning with a single consonant can be attributed to a combination of two N1/P2 complexes, temporally separated by voice-onset time (VOT). Cortical auditory-evoked potentials were recorded in seven normal-hearing young adults in response to two types of stimuli (a) simple tone bursts and (b) five monosyllabic words with different VOTs. Cortical burst responses (mainly consisting of N1 and P2) formed the basic functions for the simulation of speech-evoked potentials. Actually, two basic functions were created with respect to different VOTs of the speech sounds. An optimization procedure was used to determine the relative contributions of the two N1/P2 complexes. Speech-evoked potentials differed clearly across the stimuli. In all subjects, close matches of the synthetic and the measured waveforms could be gained for all speech sounds. The relative magnitudes of the constituent complexes differed among stimuli. The auditory-evoked response to a monosyllabic speech sound with short VOT can be represented by two overlapping N1/P2 complexes-one to syllable onset and the second to vowel onset. The temporal separation between the two components is well predicted by VOT, but the relative amplitudes vary across syllables. Observed variability in the fitting accuracy across subjects is small.


Correlates of hair cortisol concentrations in disadvantaged young children.
Children from highly disadvantaged families tend to experience worse health, educational, and job outcomes than less disadvantaged peers. However, the mechanisms underlying these relationships remain to be explicated. In particular, few studies have investigated the relationships between the psychosocial influences that children are exposed to early in life and longer term cortisol output. This study aims to contribute to the literature by exploring how disadvantaged young children's experiences of family adversity, and parenting and family functioning, are related to their long-term cortisol levels. A sample of 60 children (26 males, mean = 4.25 years, SD = 1.68) and their mothers (mean = 34.18 years, SD = 7.11) from a low-income population took part in a single assessment. Mothers completed questionnaires on the family environment, parenting practices, and child behaviour. Children provided a hair sample for cortisol assay and anthropometric measures. A parsimonious multivariate regression model (including potential predictors identified by a selection algorithm) was used to investigate the correlates of hair cortisol concentration (HCC) in children. Higher levels of social exclusion, being male, and younger age were each associated with higher HCC. Maternal nurturing and emotion coaching were associated with lower HCC. Findings suggest that chronic stress may underlie relationships between adversity and its long-term effects and that HCC offers a promising method for examining chronic stress in children and evaluating interventions by which it can be ameliorated.


pIP40a, a type 1 IncC plasmid from 1969 carries the integrative element GIsul2 and a novel class II mercury resistance transposon.
The 167.5kb sequence of the conjugative IncC plasmid pIP40a, isolated from a Pseudomonas aeruginosa in 1969, was analysed. pIP40a confers resistance to kanamycin, neomycin, ampicillin, sulphonamides and mercuric ions, and several insertions in a type 1 IncC backbone were found, including copies of IS3, Tn1000 and a novel mercury resistance transposon, Tn6182. The antibiotic resistance genes were in two locations. Tn6023, containing the aphA1 kanamycin and neomycin resistance gene, is in a partial copy of Tn1/Tn2/Tn3 (blaTEM, ampicillin resistance) in the kfrA gene, and the sul2 sulphonamide resistance gene is in the integrative element GIsul2 in the position of ARI-B islands. The 11.5kb class II transposon Tn6182 is only distantly related to other class II transposons, with at most 33% identity between the TnpA of Tn6182 and TnpA of other group members. In addition, the inverted repeats are 37bp rather than 38bp, and the likely resolution enzyme is a tyrosine recombinase (TnpI). Re-annotation of GIsul2 revealed genes predicted to confer resistance to arsenate and arsenite, but resistance was not detected. The location of GIsul2 confirms it as the progenitor of the ARI-B configurations seen in many IncC plasmids isolated more recently. However, GIsul2 has integrated at the same site in type 1 and type 2 IncC plasmids, indicating that it targets this site. Analysis of the distribution of GIsul2 revealed that it in addition to its chromosomal integration site at the 3'-end of the guaA gene, it has also integrated into other plasmids, increasing its mobility.


Cataract surgery in treated retinoblastoma eyes: A study of 29 eyes.
To study the outcomes of cataract surgery in treated retinoblastoma (RB) eyes. Retrospective study of 29 eyes of 27 patients. Based on International Classification of Intraocular Retinoblastoma, tumors belonged to group B (n = 3, 10%), C (n = 1, 4%), D (n = 10, 34%), and E (n = 3, 10%). The remaining 12 eyes (41%) had regressed tumors on presentation due to prior treatment. The RB treatment details included intravenous chemotherapy (n = 24, 83%), external beam radiotherapy (n = 14, 48%), and others. The mean time interval between tumor regression and cataract surgery was 51 months (median, 26 months; range, 6-245 months). The post-operative visual acuity was 20/200 or better in 12 (41%) eyes. Overall, 16 (55%) eyes displayed improvement of vision post-cataract surgery, while 13 (45%) eyes had no improvement in vision. The complications of cataract surgery included visual axis opacification (n = 15, 52%), pupillary membrane (n = 4, 14%), hyphema (n = 1, 3%), and extraocular tumor extension (n = 1, 3%). Clearer fundus view post-surgery revealed underlying tumor edge recurrence in 1 (3%) eye, and two (7%) patients had tumor recurrence at a mean interval of 8 months (median, 8 months; range, 7-8 months) following cataract extraction. Globe salvage was achieved in 26 (90%) eyes over a mean follow-up period of 103 months (median, 91 months; range, 19-267 months). Cataract surgery in treated RB is safe with vision salvage in 55% eyes and globe salvage in 90% eyes. Though there is a risk of extraocular tumor extension, its occurrence is rare (3%).


A case of acampomelic campomelic dysplasia.
Acampomelic campomelic dysplasia is a rare variant of campomelic dysplasia syndrome affecting bone and connecting tissue. This syndrome is implicated by the absence of bowed limbs. Affected children have a characteristically smooth facial profile and are born with respiratory distress. A 15 day old Turkish boy presented with a small flat face, dolicocephalic head, proptotic eyes, short neck, low-set ears and a small thoracic cage. Limbs were mesomelically short and bilateral talipes equinovarus was present. The radiological findings indicated hypoplastic scapulae, narrow ribs, small thorax, thin claviculaes, and small iliac wings. Angulation of the femur, tibia and humerus was not observed. Our case, suited to acampomelic campomelic dysplasia, is discussed with differential diagnosis and compared with previously reported cases of the syndrome.


An emerging model organism Caenorhabditis elegans for alternative pre-mRNA processing in vivo.
A nematode Caenorhabditis elegans is an intron-rich organism and up to 25% of its pre-mRNAs are estimated to be alternatively processed. Its compact genomic organization enables construction of fluorescence splicing reporters with intact genomic sequences and visualization of alternative processing patterns of interest in the transparent living animals with single-cell resolution. Genetic analysis with the reporter worms facilitated identification of trans-acting factors and cis-acting elements, which are highly conserved in mammals. Analysis of unspliced and partially spliced pre-mRNAs in vivo raised models for alternative splicing regulation relying on specific order of intron excision. RNA-seq analysis of splicing factor mutants and CLIP-seq analysis of the factors allow global search for target genes in the whole animal. An mRNA surveillance system is not essential for its viability or fertility, allowing analysis of unproductively spliced noncoding mRNAs. These features offer C. elegans as an ideal model organism for elucidating alternative pre-mRNA processing mechanisms in vivo. Examples of isoform-specific functions of alternatively processed genes are summarized. WIREs RNA 2017, 8:e1428. doi: 10.1002/wrna.1428 For further resources related to this article, please visit the WIREs website.


Refraction correction and coordinate displacement compensation in nearshore bathymetry using ICESat-2 lidar data and remote-sensing images.
In nearshore bathymetry based on the Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2), water refraction causes a position displacement of the seafloor signal photon, decreasing the bathymetric accuracy. A novel refraction-correction method is proposed for the ICESat-2. Based on the experimental results and statistical analysis, it is illustrated that the displacement in elevation direction reaches several meters at the relative depth. The displacement in the along- and cross-track directions is very small, ranging from millimeters to centimeters. Finally, the relationship of refraction displacements with various incident angles and water depths is analyzed in detail, revealing the nearshore bathymetry characteristics of ICESat-2.


CVD mortality, 1968-1978: observations and implications.
U.S. multiple cause of death data were examined for the period 1968-1978. Specifically, the role of cerebrovascular disease mortality as an underlying and associated cause of death was studied. The number of deaths where cerebrovascular disease was cited as the underlying cause of death declined much faster than the number of deaths where cerebrovascular disease was cited as the associated cause of death. This trend is indicative of a possible change in the role of cerebrovascular disease as an associated cause of death. Cause elimination life tables were constructed for cerebrovascular disease as the underlying cause of death and as any cause of death. In the general population, eliminating stroke as a cause of death is projected to have less impact in 1978 than in 1968, for men than for women, and for whites than for nonwhites. Tables were also constructed to examine the life expectancy gains for the group of individuals who died of cerebrovascular disease. For these individuals, the gain in life expectancy at birth ranges from 9 years for white males to 18 years for nonwhite females.


Asymptomatic bacteriuria among elderly and middle-aged rural community-dwellers in South-Western Nigeria.
Asymptomatic bacteriuria in elderly individuals has been well described in institutionalized settings, but to a lesser extent in the community. The purpose of this study was to determine the pathogens responsible for asymptomatic bacteriuria in elderly and middle-aged individuals in Alajue-Ede, South-Western Nigeria, and to identify any associated factors. Mid-stream urine samples were collected from apparently healthy elderly and middle-aged volunteers who were participating in community health screening. Samples were processed and bacterial isolates were identified following standard procedures. In total, 128 volunteers (48 men, 76 women) participated in the study. Twenty-eight (22.6%) urinary pathogens were isolated, comprising Klebsiella species in five (17.9%), Pseudomonas aeruginosa in one (3.6%), Escherichia coli in 19 (67.9%), and Proteus species in three (10.7%) cases. Women were identified as being at higher risk of asymptomatic bacteriuria, and the prevalence also increased with increasing age in men. The elderly in this community have a high prevalence of asymptomatic bacteriuria, and screening for comorbid medical conditions may be of benefit.


The difference on the osteogenic differentiation between periodontal ligament stem cells and bone marrow mesenchymal stem cells under inflammatory microenviroments.
Periodontitis is a major cause of tooth loss in adults and periodontal ligament stem cells (PDLSCs) is the most favorable candidate for the reconstruction of tissues destroyed by periodontal diseases. However, pathological alterations caused by inflammatory insults might impact the regenerative capacities of these cells. Bone-marrow-derived human mesenchymal stem cells (hBMSCs) would accelerate alveolar bone regeneration by transplantation, compared to PDLSCs. Therefore, a better understanding of the osteogenic differentiation between PDLSCs and BMSCs in inflammatory microenviroments is therefore warranted. In this study, human PDLSCs were investigated for their stem cell characteristics via analysis of cell surface marker expression, colony forming unit efficiency, osteogenic differentiation and adipogenic differentiation, and compared to BMSCs. To determine the impact of both inflammation and the NF-κβ signal pathway on osteogenic differentiation, cells were challenged with TNF-α under osteogenic induction conditions and investigated for mineralization, alkaline phosphatase (ALP) activity, cell proliferation and relative genes expression. Results showed that PDLSCs exhibit weaker mineralization and ALP activity compared to BMSCs. TNF-α inhibited genes expression of osteogenic differentiation in PDLSCs, while, it stimulates gene expressions (BSP and Runx2) in BMSCs. Enhanced NF-κβ activity in PDLSCs decreases expression of Runx2 but it does not impede the osteogenic differentiation of BMSCs. Taken together, these results may suggest that the BMSCs owned the stronger immunomodulation in local microenvironment via anti-inflammatory functions, compared to PDLSCs.


Diagnostic utility of biomarkers for neonatal sepsis--a systematic review.
Neonatal sepsis is a major cause of morbidity and mortality. Early diagnosis and treatment of the neonate with suspected sepsis are essential to prevent life-threatening complications. Diagnosis of neonatal sepsis is a challenge due to non-specific clinical signs and the fact that infection markers are difficult to interpret in the first and critical phase of neonatal sepsis. The objective of the present study was to systematically evaluate existing evidence of the diagnostic utility of biomarkers for prediction of sepsis in neonates. We conducted a systematic literature search performed in PubMed and Embase. The study population was neonates with gestation age > 24 weeks in their first 28 days of life with suspected sepsis. The included manuscripts were rated due to criteria from a modified rating scale developed by Douglas Altman. Of 292 potentially relevant manuscripts, 77 fulfilled the inclusion and exclusion criteria; 16 (21%) were rated as high-quality studies. C-reactive protein (CRP) was the most extensively studied biomarker evaluated. The high-quality studies indicated that the acute phase protein serum amyloid A had high sensitivity, both at onset of symptoms and 2 days after. The studies evaluating serum amyloid A presented a variable positive predictive value (PPV, 0.67 and 0.92) with a high negative predictive value (NPV, 0.97 and 1.00). The existing evidence of the diagnostic value of serum amyloid A for neonatal sepsis showed promising results, and should be further investigated in clinical settings.


[The immune enhancement of the C3 to the Escherichia coli vaccine].
C3b was separated and purified from the SPF chicken serum. It was linked with E. coli antigen by the glutaral. 11 days aged SPF chicken were immunized by the complex antigen and the chickens of control group were immunised by the FCA- E. coli antigen . They were boosted at the age of 18 day. The immune response was monitored by an enzyme-linked immunosorbent assay(ELISA) for anti-E. coli anitibody. The ELISA results indicated that during the early several weeks, IgG titers elicited by FCA (FCA-E. coli) were higher than those elicited by C3 (C3b-E. coli), but decreased rapidly after a peak around the end of 4th week from being immunized. Chickens immunized with C3b always gave increased response, and the IgG titers were equal to that of FCA at the end of 5th week from being immunized and then higher and higher than that of FCA. Thus the adjuvant effect of C3b is different from that of FCA, it could induce production of memory cell and make the antigens stimulate immune cells consistently and stably.


Streptococcus faecalis mutants defective in regulation of cytoplasmic pH.
We have isolated two acid-sensitive mutants of Streptococcus faecalis (ATCC 9790), designated AS13 and AS25, which grew at pH 7.5 but not at pH below 6.0. The ionophore gramicidin D, which collapsed the pH gradient between the cytoplasm and the medium, had little effect on the growth of these mutants, indicating that growing cells maintain only a small pH gradient. In the presence of gramicidin D the growth rates of the parent and mutant strains were identical over a range of pH values. When glucose was added to a cell suspension at pH 6.4, the parent strain generated a pH gradient of 1.0 unit, interior alkaline; AS13 generated a pH gradient of only 0.5 units, and AS25 generated no measurable pH gradient. The proton permeability of the mutant strains was the same as that of the parent strain. These results suggest that a cytoplasmic pH of around 7.5 is required for the growth of the cells and that the mutant strains are unable to establish a neutral cytoplasmic pH in acidic medium because of damage to the regulatory system of the cytoplasmic pH. Mutant strains also have a reduced capacity to extrude protons and take up potassium. Therefore, it is likely that these cation transport systems are involved in the regulation of cytoplasmic pH.


Replacement of the proximal humerus with a ceramic prosthesis: a preliminary report.
Insertion of a multicomponent ceramic prosthesis with extracortical fixation to the conically reamed shaft of the humerus was performed in 7 patients after resection of 4 malignant and 3 benign tumors of the proximal humerus. The length of the replacement ranged from 9 to 18 cm. Fixation was secure in all but one patient, who sustained a fracture through the proximal humerus. Subluxation occurred in 3 patients but posed no difficulty, except in one patient who required revision for a dislocation. Functionally, little active motion is achieved, but the implant provides a spacer to permit efficient use of the hand and elbow. No patient has had local recurrence of the tumor. One patient died one year postoperatively from an unrelated second primary cancer. Although the preliminary results are encouraging, further investigations are necessary on the mechanical aspects of the cone fixation principle and of the techniques of shoulder muscle reconstruction to improve the function of the prosthetic joint.


High Energy Storage Performance in La-Doped AgNbO3 Ceramics via Tape Casting.
AgNbO3-based Pb-free antiferroelectric (AFE) ceramics have attracted increasing interest owing to their excellent potential in energy storage applications. Herein, a high recoverable energy storage density (Wrec) of 7.62 J/cm3 is realized in La-doped AgNbO3 ceramics prepared via tape casting. The high Wrec is attributed to high breakdown strength Eb of 380 kV/cm induced by dense microstructure as well as fine grain size and enhanced AFE stability stemming from M2 phase and reduced tolerance factor t. The high Wrec exceeding 6 J/cm3 was maintained in a wide temperature range of 20-150 °C and exhibited frequency stability with less than 8% variation in a range of 1-200 Hz. The discharge energy density Wd exhibited temperature stability at 30-110 °C with less than 9% variation. Our research provides a good method for producing AgNbO3-based ceramics having high energy storage performances.


Assessment of Ready-to-Use Freeze-dried Immobilized Biocatalysts as Innovative Starter Cultures in Sourdough Bread Making.
In the present study the effect of innovative biocatalysts as starter cultures in sourdough bread making was explored. The biocatalysts consisted of Lactobacillus paracasei K5 and Lactobacillus bulgaricus ATCC 11842 (in single and mixed form), immobilized on delignified wheat bran (DWB), and freeze dried without cryoprotectants. The parameters monitored were physicochemical characteristics, mold and rope spoilage appearance, volatile composition, and organoleptic characteristics. Results obtained showed that both biocatalysts exhibit good fermentative activity. However, the best results were achieved when freeze-dried immobilized L. paracasei K5 was applied as a single culture. In particular, the produced bread had a higher acidity (8.67 mL 0.1 N NaOH) and higher organic load (2.90 g/kg lactic acid and 1.11 g/kg acetic acid). This outcome was the main reason why this bread was preserved more regarding mold spoilage (14 days) and rope spoilage (12 days), respectively. In addition, the employment of freeze-dried immobilized L. paracasei K5 led to bread with better aromatic profile in terms of concentrations and number of volatile compounds produced as gas chromatography/mass spectrometry (GC/MS) analysis proved. Finally, no significant differences were observed through sensorial tests. Last but not least, it should be highlighted that the used microorganisms were cultured in cheese whey, minimizing the cost of the proposed biotechnological procedure.


Disruption of the structural gene for farnesyl diphosphate synthase in Escherichia coli.
The chromosomal ispA gene encoding farnesyl diphosphate synthase of Escherichia coli was disrupted by inserting a neo gene cassette. The null ispA mutants were viable. The growth yield of the mutants was 70% to 80% of that of the wild-type strain under aerobic conditions, and was almost the same as the wild-type under anaerobic conditions. The levels of ubiquinone-8 and menaquinone-8 were both significantly lower (less than 13% and 18% of normal, respectively) in the mutants than in the wild-type. The undecaprenyl phosphate level in the mutants was modestly lower (40% to 70% of normal) than in the wild-type strain. Thus the synthesis of all-E-octaprenyl diphosphate, the precursor of ubiquinone-8 and menaquinone-8, was decreased more severely than that of Z,E-mixed undecaprenyl diphosphate, the precursor of undecaprenyl monophosphates, under the conditions where the synthesis of farnesyl diphosphate was decreased. The condensation of isopentenyl diphosphate with dimethylallyl diphosphate was detected in the cell-free extracts of the mutants, although it was 5% of that in the wild-type strain. A low level of farnesyl diphosphate seems to be synthesized in the mutants by other prenyltransferases such as octaprenyl diphosphate synthase or undecaprenyl diphosphate synthase.


Fat emulsions and lung function.
IVFE infusion can impair lung function in healthy adults, premature infants, and adults with pre-existing lung injury, and in experimental animals with acute injury. Although all observed IVFE-related lung dysfunction was initially attributed to the temporally associated hyperlipemia, this explanation may in fact be correct only with fat overload syndrome. When serum triglyceride levels are in a more appropriate range, all subsequent studies have shown the same alterations in lung function unrelated to triglyceride increases and indomethacin-related blocking of lung function impairment, despite comparable serum triglyceride increases. Furthermore, our studies with Liposyn demonstrated the most significant increases in serum triglyceride levels, but the smallest PaCO2 and PaO2 changes. In general, the lung function abnormalities associated with IVFE infusion have thus been caused by increases in VA/Q inequalities. Although elucidation of the relationship between IVFE-related increased PG production and secondary VA/Q changes may be of significant physiologic import, the PaO2 and PaCO2 changes even with pre-existing lung injury have generally not been of sufficient magnitude to be of much clinical significance. The IVFE-related increases in plasma PG concentrations may, however, still have significant nonpulmonary clinical effects related to known or postulated consequences of increased plasma PG concentrations, including effects on ductus arteriosus patency, retinal and cerebral blood flow, and immune competence.


Comparison of population-averaged and subject-specific approaches for analyzing repeated binary outcomes.
Several approaches have been proposed to model binary outcomes that arise from longitudinal studies. Most of the approaches can be grouped into two classes: the population-averaged and subject-specific approaches. The generalized estimating equations (GEE) method is commonly used to estimate population-averaged effects, while random-effects logistic models can be used to estimate subject-specific effects. However, it is not clear to many epidemiologists how these two methods relate to one another or how these methods relate to more traditional stratified analysis and standard logistic models. The authors address these issues in the context of a longitudinal smoking prevention trial, the Midwestern Prevention Project. In particular, the authors compare results from stratified analysis, standard logistic models, conditional logistic models, the GEE models, and random-effects models by analyzing a binary outcome from two and seven repeated measurements, respectively. In the comparison, the authors focus on the interpretation of both time-varying and time-invariant covariates under different models. Implications of these methods for epidemiologic research are discussed.


[Pedicled fibroma of the extrahepatic bile ducts].
It is reported on the very rare occurrence of a benign tumor in common hepatic bile duct of a 33-year-old woman, associated with obstructive jaundice. Clinical diagnosis and treatment are described, histological typing like fibroblastic tumor with neurogenic parts are discussed and a short review of the literature is given.


LamB (maltoporin) of Salmonella typhimurium: isolation, purification and comparison of sugar binding with LamB of Escherichia coli.
LamB (maltoporin) of Salmonella typhimurium was found to be more strongly associated with the murein than OmpF. It was purified in one step using a hydroxyapatite (HTP) column. Reconstitution of the pure protein with lipid bilayer membrane showed that LamB of S. typhimurium formed small ion-permeable channels with a single channel conductance of about 90 pS in 1 M KCl and some preference for cations over anions. The conductance concentration curve was linear, which suggested that LamB of S. typhimurium does not contain any binding site for ions. Pore conductance was completely inhibited by the addition of 20 mM maltotriose. Titration of the LamB-induced membrane conductance with different sugars, including all members of the maltooligosaccharide series up to seven glucose residues, suggested that the channel contains, like LamB (maltoporin) of Escherichia coli, a binding site for sugars. The binding constant of sugars of the maltooligosaccharide series increased with increasing number of glucose residues up to five (saturated). Small sugars had a higher stability constant for sugar binding relative to LamB of E. coli. The advantage of a binding site inside a specific porin for the permeation of solutes is discussed with respect to the properties of a general diffusion porin.


Intrauterine insemination versus intracervical insemination in donor sperm treatment.
The first-line treatment in donor sperm treatment consists of inseminations that can be done by intrauterine insemination (IUI) or by intracervical insemination (ICI). To compare the effectiveness and safety of intrauterine insemination (IUI) and intracervical insemination (ICI) in women who start donor sperm treatment. We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL in October 2016, checked references of relevant studies, and contacted study authors and experts in the field to identify additional studies. We searched PubMed, Google Scholar, the Grey literature, and five trials registers on 15 December 2017. We included randomised controlled trials (RCTs) reporting on IUI versus ICI in natural cycles or with ovarian stimulation, and RCTs comparing different cointerventions in IUI and ICI. We included cross-over studies if pre-cross-over data were available. We used standard methodological procedures recommended by Cochrane. We collected data on primary outcomes of live birth and multiple pregnancy rates, and on secondary outcomes of clinical pregnancy, miscarriage, and cancellation rates. We included six RCTs (708 women analysed) on ICI and IUI in donor sperm treatment. Two studies compared IUI and ICI in natural cycles, two studies compared IUI and ICI in gonadotrophin-stimulated cycles, and two studies compared timing of IUI and ICI. There was very low-quality evidence; the main limitations were risk of bias due to poor reporting of study methods, and serious imprecision.IUI versus ICI in natural cyclesThere was insufficient evidence to determine whether there was any clear difference in live birth rate between IUI and ICI in natural cycles (odds ratio (OR) 3.24, 95% confidence interval (CI) 0.12 to 87.13; 1 RCT, 26 women; very low-quality evidence). There was only one live birth in this study (in the IUI group). IUI resulted in higher clinical pregnancy rates (OR 6.18, 95% CI 1.91 to 20.03; 2 RCTs, 76 women; I² = 48%; very low-quality evidence).No multiple pregnancies or miscarriages occurred in this study.IUI versus ICI in gonadotrophin-stimulated cyclesThere was insufficient evidence to determine whether there was any clear difference in live birth rate between IUI and ICI in gonadotrophin-stimulated cycles (OR 2.55, 95% CI 0.72 to 8.96; 1 RCT, 43 women; very low-quality evidence). This suggested that if the chance of a live birth following ICI in gonadotrophin-stimulated cycles was assumed to be 30%, the chance following IUI in gonadotrophin-stimulated cycles would be between 24% and 80%. IUI may result in higher clinical pregnancy rates than ICI (OR 2.83, 95% CI 1.38 to 5.78; 2 RCTs, 131 women; I² = 0%; very low-quality evidence). IUI may be associated with higher multiple pregnancy rates than ICI (OR 2.77, 95% CI 1.00 to 7.69; 2 RCTs, 131 women; I² = 0%; very low-quality evidence). This suggested that if the risk of multiple pregnancy following ICI in gonadotrophin-stimulated cycles was assumed to be 10%, the risk following IUI would be between 10% and 46%.We found insufficient evidence to determine whether there was any clear difference between the groups in miscarriage rates in gonadotrophin-stimulated cycles (OR 1.97, 95% CI 0.43 to 9.04; 2 RCTs, overall 67 pregnancies; I² = 50%; very low-quality evidence).Timing of IUI and ICIWe found no studies that reported on live birth rates.We found a higher clinical pregnancy rate when IUI was timed one day after a rise in blood levels of luteinising hormone (LH) compared to IUI two days after a rise in blood levels of LH (OR 2.00, 95% CI 1.14 to 3.53; 1 RCT, 351 women; low-quality evidence). We found insufficient evidence to determine whether there was any clear difference in clinical pregnancy rates between ICI timed after a rise in urinary levels of LH versus a rise in basal temperature plus cervical mucus scores (OR 1.31, 95% CI 0.42 to 4.11; 1 RCT, 56 women; very low-quality evidence).Neither of these studies reported multiple pregnancy or miscarriage rates as outcomes. There was insufficient evidence to determine whether there was a clear difference in live birth rates between IUI and ICI in natural or gonadotrophin-stimulated cycles in women who started with donor sperm treatment. There was insufficient evidence available for the effect of timing of IUI or ICI on live birth rates. Very low-quality data suggested that in gonadotrophin-stimulated cycles, ICI may be associated with a higher clinical pregnancy rate than IUI, but also with a higher risk of multiple pregnancy rate. We concluded that the current evidence was too limited to choose between IUI or ICI, in natural cycles or with ovarian stimulation, in donor sperm treatment.


Raman dissipative soliton fiber laser mode locked by a nonlinear optical loop mirror.
Raman dissipative soliton is generated in a mode locked polarization maintaining fiber laser with a nonlinear optical loop mirror. Ultrafast Raman laser with a repetition rate of 1.23 MHz is obtained. Signal to noise ratio of the radio frequency spectrum of the Raman dissipative soliton is as high as 85 dB. As the pump power increasing, the pulse energy and the spectral width increase, while the pulse width decreases. The highest pulse energy and lowest pulse width is 1.23 nJ and 63 ps, respectively. It is the first report of Raman dissipative soliton generation from an all polarization maintaining mode locked fiber laser to the best of our knowledge. This configuration provides a method to obtain linearly-polarized ultrafast laser at flexible wavelengths.


Photobleaching kinetics of optically trapped multilamellar vesicles containing verteporfin using two-photon excitation section sign.
Two-photon excitation photodynamic therapy (TPE-PDT) is being developed as an improved treatment for retinal diseases. TPE-PDT has advantages over one-photon PDT, including lower collateral damage to healthy tissue and more precise delivery of PDT. As with one-photon PDT, there can be local photochemical depletion of oxygen during TPE-PDT. Here, we investigate model systems and live cells to measure local photosensitizer photobleaching and through it, infer local oxygen consumption in therapeutic volumes of the order 1 microm3. Multilamellar vesicles (MLV) and African green monkey kidney (CV-1) cells were used to study the TPE photobleaching dynamics of the photosensitizer, Verteporfin. It was found that in an oxygen-rich environment, photobleaching kinetics could not be modeled using a mono-exponential function, whereas in hypoxic conditions a mono-exponential decay was adequate to represent photobleaching. A biexponential was found to adequately model the oxygen-rich conditions and it is hypothesized that the fast part of the decay is oxygen-dependent, whereas the slower rate constant is largely oxygen-independent. Photobleaching recovery studies in the CV-1 cells support this hypothesis.


Investigation of radiative and nonradiative relaxation by two-photon resonant excitation in Tm3+ doped LaF3 particles.
Nano-scaled and micro-scaled Tm(3+)-doped LaF3 were prepared by a hydrothermal technique. Two-photon resonant excitation from the ground state 3H6 to the excited state 1D2 was fulfilled by two pulsed dye lasers tuned at 656 nm and 643 nm, respectively, which were resonant with the ground state absorption of 3H6 --> 3F2 and the excited state absorption of 3H4 --> 1D2. The time evolution of the corresponding state was investigated with blue upconverted emission by tuning the delay of two excitation lights. The results showed that the nonradiative relaxation of the 3F2 state was mainly affected by the confinement effect, while the radiative relaxation of 3H4 state was significantly influenced by the Tm3+ concentration.


Isolation and identification of chlorate-reducing Hafnia sp. from milk.
Chlorate has become a concern in the food and beverage sector, related to chlorine sanitizers in industrial food production and water treatment. It is of particular concern to regulatory bodies due to the negative health effects of chlorate exposure. This study investigated the fate of chlorate in raw milk and isolated bacterial strains of interest responsible for chlorate breakdown. Unpasteurized milk was demonstrated to have a chlorate-reducing capacity, breaking down enriched chlorate to undetectable levels in 11 days. Further enrichment and isolation using conditions specific to chlorate-reducing bacteria successfully isolated three distinct strains of Hafnia paralvei. Chlorate-reducing bacteria were observed to grow in a chlorate-enriched medium with lactate as an electron donor. All isolated strains were demonstrated to reduce chlorate in liquid medium; however, the exact mechanism of chlorate degradation was not definitively identified in this study.


Cancer incidence and survival among children and adolescents in Israel during the years 1998 to 2007.
Our goal was to describe childhood cancer incidence and survival in Israel and to identify demographic and epidemiologic variations among children and adolescents with cancer. We used data from the Israel National Cancer Registry to examine the incidence and survival of pediatric cancer in Israeli children aged 0 to 19 years, diagnosed during the years 1998 to 2007. Cases were analyzed according to sex, age, ethnicity, and geographic region. Among the 4255 cases of childhood cancer, there was a total age-adjusted incidence rate of 172.4 per million for children aged 0 to 19 years and 153.4 per million for children aged 0 to 14 years. The incidence rate for boys was higher than for girls (192.5 and 153.3, respectively) and higher for Jewish children than for Arab children (177.6 and 156.8, respectively). The largest groups were leukemias (22%), lymphomas (20.2%), and central nervous system tumors (17.4%). The number of new cases increased each year, but the incidence rate remained steady. The survival probability updated to December 2008 was estimated and the 5-year survival was calculated for the new cases until the end of 2003. The overall survival at 5 years was 80.8%, with 72.8% for the Arabic population and 83.2% for the Jewish population, and depended on the diagnosis. Incidence and survival in childhood cancer in Israel is at the same medium level compared with other parts of the world. This study may set the basis for investigating the genetic and environmental factors that cause pediatric cancer in Israel, delineating the genetic basis for ethnic origin disparities in survival.


Radiobiological considerations of brachytherapy.
The special radiobiological effects of low dose-rate radiation on tumors and normal tissue are in large part responsible for the effectiveness of brachytherapy. There is good reason to believe that improvement in local tumor control can be expected by the addition of chemotherapeutic agents, specifically designed radiation sensitizers, and differentiation-inducing agents, as well as by the manipulation of dose rates and dose distributions. This can be an important contribution to cancer management in the future and is an exciting area for further study.


[Blood platelets and fibrinolysis in ischemic heart disease].
The role of platelets and fibrinolysis in ischemic heart disease are discussed. The interaction lipoproteins with platelet factors may be important in therapy of ischemic heart disease.


Light-induced Hemiplegia, an Atypical Case of Retinal Steal Syndrome.
Atherosclerosis affecting the carotid arteries accounts for up to 20% of ischemic strokes 1. The clinical effects of atherosclerotic occlusive disease vary according to multiple factors, one of which is collateral circulation. In response to a chronic decrease in cerebral perfusion from atherosclerotic occlusion, alternative flow pathways, or collaterals, develop in a variety of patterns. In the setting of carotid occlusion, flow from the Circle of Willis, if complete, often comprises the main cerebral collateral network. In addition, contributions from leptomeningeal and extracranial to intracranial collaterals may develop. In the latter, reversal of flow in the ophthalmic artery can reconstitute to restore supraclinoid internal carotid artery flow. We report a case of the unusual sequela of a collateral flow pattern via the ophthalmic artery that induces a unique retinal steal phenomenon.


Effect of copper nanoparticles administered in ovo on the activity of proliferating cells and on the resistance of femoral bones in broiler chickens.
The objective of this study was to evaluate bone resistance after in ovo administration of copper nanoparticles (NanoCu) and to determine the number of cells positive for proliferating cell nuclear antigen (PCNA) in the femoral bones of broiler chickens (n = 12 per group). The study demonstrated that femoral bones from the NanoCu group were characterised by a higher weight and volume and by significantly greater resistance to fractures compared to the Control group. NanoCu promoted the proliferation of PCNA-positive cells in the long bones of chickens. A significantly higher number of PCNA-positive cells in the bones of birds in the NanoCu group compared with the Control group (137 and 122, respectively) indicate a stimulatory effect during embryogenesis. Considering the improvement in bone resistance to fractures and the effect of NanoCu on the number of PCNA-positive cells in femoral bones, NanoCu may be an alternative agent to minimise the ever-present problem of weak bones in broiler chickens.


STYK1 promotes Warburg effect through PI3K/AKT signaling and predicts a poor prognosis in nasopharyngeal carcinoma.
STYK1 (Serine/threonine/tyrosine kinase 1), a member of the receptor tyrosine kinase family, exhibits tumorigenicity in many types of cancers. Our study reveals the important role played by STYK1 in nasopharyngeal carcinoma. STYK1 is upregulated in nasopharyngeal carcinoma tissues compared with para-carcinoma. Knockdown of STYK1 inhibits nasopharyngeal carcinoma cell proliferation, migration, and invasion, while ectopic STYK1 expression significantly promoted cell proliferation, migration, and invasion abilities. In addition, we provided lines of evidence supporting the critical role of STYK1 in the regulation of glycolysis via activation of phosphoinositide 3-kinase/AKT pathway. Survival analysis reveals that STYK1 level is an independent prognostic factor for nasopharyngeal carcinoma patients. Our results indicate that STYK1 is a promising therapeutic target in nasopharyngeal carcinoma.


Systematic Review on Copper Calcium Hydroxide Nanoparticles in the Treatment of Apical Periodontitis.
Apical periodontitis is an inflammation and destruction of the periradicular tissues due to various insults to the pulp in the form of infection, trauma, and faulty dental procedures. Conditions regarding this are treated employing root canal therapy. Recent innovations show that copper calcium hydroxide nanoparticles and their electrophoresis can be used to treat apical periodontitis effectively. To evaluate the effectiveness of copper calcium hydroxide nanoparticles in the treatment of apical periodontitis, a literature search was done using PubMed, Cochrane Central Register of controlled Trials (CENTRAL), Science Direct, and Lilacs using the MeSH (Medical Subject Heading) terms Copper calcium hydroxide, apical periodontitis, nanoparticles, and electrophoresis. Of a total of 167 articles screened, 44 were full-text articles assessed for eligibility and four articles were taken for the qualitative analysis. This review was recorded according to the PRISMA GUIDELINES. Four randomized controlled trials were included in the review process. The copper calcium hydroxide particles were compared with other root canal medicament materials. It was found that copper calcium hydroxide and its electrophoresis were used in the treatment of apical periodontitis and were found to be one of the effective methods. Copper calcium hydroxide nanoparticles were effective against the destruction of the periradicular tissues.


Clinicopathological Features of 15 Occult and 178 Clinical Pancreatic Ductal Adenocarcinomas in 8339 Autopsied Elderly Patients.
The aim of the study was to investigate the clinicopathological features of pancreatic cancer at different stages using autopsy results. We retrospectively evaluated 8399 consecutive cases of autopsy performed between 1972 and 2013 at our geriatric hospital. Macroscopic pancreatic lesions were detected in 6.13% of the cases. Primary and secondary pancreatic tumors were observed in 2.88% and 2.10% of the cases, respectively. Most primary tumors were invasive ductal adenocarcinomas (193 cases [2.31%]; mean patient age, 78.09 years) with a peak incidence at 50 to 59 years. Occult invasive ductal adenocarcinoma was discovered incidentally in 15 cases, with distant metastasis present in 26.67% of those. Microscopically, occult and advanced tumors exhibited similar characteristics such as hyalinized fibrous stroma, necrosis, invasion into vessels, peripancreatic fat tissues, and extrapancreatic nerve plexus. Mucin 1 and 2 immunohistochemical expression levels were also similar. Occult cancer incidence increased with age. Patients aged 85 years or older had shorter survival, a small tumor size, and a low incidence of lymph node metastasis. Approximately 8% of pancreatic invasive ductal adenocarcinomas progressed asymptomatically and were discovered incidentally at autopsy. Pancreatic cancers in elderly patients tend to progress asymptomatically, but once symptoms develop, they are more often fatal than those in younger patients.


[Laryngeal papillomatosis in Mali. Apropos of 19 cases collected at the Gabriel Touré Hospital of Bamako].
From 1994 to 1999, 19 cases of laryngeal papillomatosis were observed. The sex-ratio M/F was 0.9 and the mean age 10 years. The motive for consulting was dyspnoea for 45% of the cases and in all these cases resulted in emergency tracheotomy. The only available means of intervention was peeling under general anaesthesia. An anatomopathological examination could be carried out for only 63.1% of cases. Prevalence of the disease has been under-estimated for reasons of late diagnosis and the inaccessibility to health structures for some cases.


Emotional labour and aboriginal maternal infant care workers: The invisible load.
The term 'emotional labour' has been used to describe the competing demands on midwives to empathize with clients whilst maintaining a level of professional detachment. Previous research indicates that when individuals experience difficulty managing these emotions, burnout may result. Aboriginal health care workers often have roles with large emotional demands, as they are relied upon heavily to engage clients in care. However, the concept of emotional labour has received little attention in relation to this group. To explore potential sources of emotional labour for Aboriginal Maternal Infant Care workers in a maternity care program for Aboriginal women in South Australia. The program involves these workers providing care for women in partnership with midwives. We employed a phenomenological approach. Thirty in-depth interviews were conducted with staff and clients of the program. Recorded interviews were transcribed and coded and emerging themes identified. This workforce undertakes extensive emotional labour. Key sources include the cultural and family obligations they have to clients, complex social needs of many clients, and potential for community backlash when poor perinatal outcomes occur. A lack of respect for the role within the workplace further contributes to these experiences. This study found that the responsibilities inherent to the role as both cultural broker and carer create significant emotional labour for workers. Recommendations to address this and enhance the sustainability of this workforce include: recognition and valuing of emotional work by management and other staff, enhancing cultural awareness training, and building stress-relieving activities into the workplace.


Cytotoxicity and apoptosis-inducing activity of bisphenol A and hydroquinone in HL-60 cells.
BPA (bisphenol A or 2,2-bis(4-hydroxy-phenol)propane) and hydroquinone (HQ, 1,4-benzenediol) are present in dental resin materials, and small quantities of these substances may be eluted from the resins. Recently, attention has focused on the estrogen-like and carcinogenic adverse effects of BPA and HQ. Thus, it is important to investigate the cytotoxicity and apoptosis-inducing activity of these compounds. BPA and HQ reduced the viable cell number of human promyelocytic leukemia (HL-60), human oral squamous cell carcinoma (HSC-2) and human submandibular gland (HSG) cell lines in a concentration-dependent manner. The cytotoxic activity of HQ, but not of BPA, was significantly reduced by the addition of N-acetyl-L-cysteine (NAC). In biomimetic studies of the prooxidant/antioxidant activity of thiols during oxidation of BPA or HQ, the radical-scavenging activities of mixtures of BPA or HQ and 2-mercapto-1-methylimidazole (MMI, a thiol) were investigated by the induction period method. BPA without MMI showed a higher induction period (antioxidant activity) than did HQ, but BPA with MMI did not cause oxygen uptake. In contrast, HQ with MMI caused oxygen uptake, suggesting formation of MMI thiyl radicals during oxidation of HQ followed by reaction with molecular oxygen. This indicates that HQ may produce intracellular reactive oxygen species (ROS) and provides an explanation for the decrease in the cytotoxicity of HQ by NAC. BPA induced internucleosomal DNA fragmentation, a biochemical marker of apoptosis, only in HL-60 cells. BPA activated caspase-9 and caspase-3, suggesting induction of apoptosis via caspase activation by the caspase recruitment domain. The cytotoxicity of BPA was 2-fold less than that of HQ, whereas the apoptosis-inducing activity of BPA was 10-fold less than that of HQ.


Axonal injury-dependent induction of the peripheral benzodiazepine receptor in small-diameter adult rat primary sensory neurons.
The peripheral benzodiazepine receptor (PBR), a benzodiazepine but not gamma-aminobutyric acid-binding mitochondrial membrane protein, has roles in steroid production, energy metabolism, cell survival and growth. PBR expression in the nervous system has been reported in non-neuronal glial and immune cells. We now show expression of both PBR mRNA and protein, and the appearance of binding of a synthetic ligand, [(3)H]PK11195, in dorsal root ganglion (DRG) neurons following injury to the sciatic nerve. In naïve animals, PBR mRNA, protein expression and ligand binding are undetectable in the DRG. Three days after sciatic nerve transection, however, PBR mRNA begins to be expressed in injured neurons, and 4 weeks after the injury, expression and ligand binding are present in 35% of L4 DRG neurons. PBR ligand binding also appears after injury in the superficial dorsal horn of the spinal cord. The PBR expression in the DRG is restricted to small and medium-sized neurons and returns to naïve levels if the injured peripheral axons are allowed to regrow and reinnervate targets. No non-neuronal PBR expression is detected, unlike its putative endogenous ligand the diazepam binding inhibitor (DBI), which is expressed only in non-neuronal cells, including the satellite cells that surround DRG neurons. DBI expression does not change with sciatic nerve transection. PBR acting on small-calibre neurons could play a role in the adaptive survival and growth responses of these cells to injury of their axons.


E-health: an overview of the uses of the Internet, social media, apps, and websites for mood disorders.
The current article defines and surveys E-health: Internet and technology-guided interventions and tools useful for mood disorders. E-health encompasses many categories, including computerized self-help strategies, online psychotherapy, websites that provide information, social media approaches including Facebook, Internet forums for health discussions, personal blogs, and videogames. Multiple tools exist to assess and document symptoms, particularly mood charts. Although all of these approaches are popular, only online psychotherapy and videogames have actually been evaluated in studies to evaluate both validity and efficacy. The face validity of social communication strategies including social media and blogs is strong, with clear implications for stigma reduction and peer support. Informational websites continue to be primary sources of psychoeducation on mental disorders. Social media sites have widespread use by the public and a profusion of health discussions and tools, but without published research evaluation of efficacy. E-health strategies, particularly online psychotherapy and tools to document symptoms, are useful and likely effective. Social communication strategies show enormous popularity, but urgently require research evaluation for impact.


[Pulmonary microcytoma].
111 patients were treated for lung cancer in 1980-1985. Small cell carcinomas accounted for 9% of the various histological types. The cases classified by TNM were treated by radical surgery where possible. There were no cases of disease free survival at two years.


Stretchable, Stable, and Degradable Silk Fibroin Enabled by Mesoscopic Doping for Finger Motion Triggered Color/Transmittance Adjustment.
As a kind of biocompatible material with long history, silk fibroin is one of the ideal platforms for on-skin and implantable electronic devices, especially for self-powered systems. In this work, to solve the intrinsic brittleness as well as poor chemical stability of pure silk fibroin film, mesoscopic doping of regenerated silk fibroin is introduced to promote the secondary structure transformation, resulting in huge improvement in mechanical flexibility (∼250% stretchable and 1000 bending cycles) and chemical stability (endure 100 °C and 3-11 pH). Based on such doped silk film (SF), a flexible, stretchable and fully bioabsorbable triboelectric nanogenerator (TENG) is developed to harvest biomechanical energy in vitro or in vivo for intelligent wireless communication, for example, such TENG can be attached on the fingers to intelligently control the electrochromic function of rearview mirrors, in which the transmittance can be easily adjusted by changing contact force or area. This robust TENG shows great potential application in intelligent vehicle, smart home and health care systems.


A visual and semantic locus to beneficial effects of verbalization on face memory.
We examined the effect of verbally describing a face on face memory as assessed in an old-new recognition task. Verbal facilitation, measured by a difference between verbalization and control conditions, was greater for upright than for inverted faces and greater for unfamiliar than for familiar faces. We propose that generating a verbal description enhances the processing of global visual information that differentiates an individual face from other faces that are encountered and also improves recognition through the association of visually derived semantic information. Verbalization enhances visual and semantic distinctiveness in memory.


Effectiveness of photobiomodulation with low-level lasers on the acceleration of orthodontic tooth movement: a systematic review and meta-analysis of split-mouth randomised clinical trials.
Although several studies have evaluated the effect of low-level laser therapy (LLLT) on orthodontic movement acceleration, results are still inconsistent. Such inconsistencies may be attributed to the differences in the LLLT application protocols, especially in terms of wavelength ranges. Objective: (i) to assess the clinical effects of LLLT on the acceleration of orthodontic movement and (ii) to establish the most effective LLLT wavelength to accelerate tooth movement during orthodontic treatments. MEDLINE (PubMed), Scopus, ScienceDirect, and LILACS were searched from inception to October 2022. Inclusion criteria: Split-mouth randomised clinical trials (RCTs) on systemically healthy patients reporting the effect of LLLT in accelerating orthodontic movements, specifically retraction of canines. The risk of bias was assessed using RoB-2. A random effect model was applied. Nineteen RCTs met the inclusion criteria for qualitative synthesis, and eighteen RCTs were included in the quantitative synthesis. Seventeen studies were rated as at some concerns of bias and two studies were classified as having a low risk of bias. In general terms, this systematic review and meta-analysis presents a moderate risk of bias. Findings of this systematic review and meta-analysis point to a tendency for faster orthodontic dental movement in the groups receiving LLLT treatment during the first (OR of 0.28 95% CI (0.07 to 0.48)), second (OR of 0.52 95% CI (0.31 to 0.73)), and third (OR of 0.41 95% CI (0.03 to 0.79)) month follow-up. Wavelengths ≤ 810 nm and energy density values ≤ 5.3 J/cm2 were associated with faster orthodontic tooth movement.