Effects of auricular acupuncture on anthropometric, lipid profile, inflammatory, and immunologic markers: a randomized controlled trial study.
A randomized controlled clinical trial was performed to examine the effectiveness of auricular acupuncture on body weight loss and its impact on lipid profile, and immunologic and inflammatory markers in obese subjects. Participants (n=204) were randomized to therapeutic acupuncture and control groups. Subjects received authentic (cases) or sham (controls) acupuncture for 6 weeks (first period) in combination with a low-calorie diet. In the next 6 weeks (second period), the low-calorie diet was used on its own. Subjects were assessed at the beginning and 6 and 12 weeks later. In addition to anthropometric and lipid parameters, serum anti-heat shock protein (Hsp)-27, 60, 65, 70 and high sensitive C-reactive protein (hs-CRP) levels were assessed. In the first period, anthropometric parameters and hs-CRP changed significantly in both groups, while significant changes in anti-Hsp antibodies were only observed in case subjects. In the second period, which shows the sustainable effects of acupuncture, changes in anthropometric parameters were more prominent in controls, while significant reductions in the group receiving authentic acupuncture were maintained for anti-Hsp antibodies. A comparison between the first and second period in both groups showed that the changes for most of the parameters were more significant in the first period. Comparison between cases and controls showed that authentic acupuncture was more effective in reducing the levels of anthropometric factors and anti-Hsp antibodies but not hs-CRP. Auricular acupuncture in combination with diet restriction was effective for weight loss and dyslipidemia. Moreover, it was found that it has immunomodulatory but not anti-inflammatory effects on the immune system by regulation of the levels of anti-Hsp antibodies.


Identification of a copper-transporting ATPase involved in biosynthesis of A. flavus conidial pigment.
Conidia are asexual spores and play a crucial role in fungal dissemination. Conidial pigmentation is important for tolerance against UV radiation and contributes to survival of fungi. The molecular basis of conidial pigmentation has been studied in several fungal species. In spite of sharing the initial common step of polyketide formation, other steps for pigment biosynthesis appear to be species-dependent. In this study, we isolated an Aspergillus flavus spontaneous mutant that produced yellow conidia. The underlying genetic defect, a three-nucleotide in-frame deletion in the gene, AFLA_051390, that encodes a copper-transporting ATPase, was identified by a comparative genomics approach. This genetic association was confirmed by disruption of the wild-type gene. When yellow mutants were grown on medium supplemented with copper ions or chloride ions, green conidial color was partially and nearly completely restored, respectively. Further disruption of AFLA_045660, an orthologue of Aspergillus nidulans yA (yellow pigment) that encodes a multicopper oxidase, in wild type and a derived strain producing dark green conidia showed that it yielded mutants that produced gold conidia. The results placed formation of the gold pigment after that of the yellow pigment and before that of the dark green pigment. Using reported inhibitors of DHN-melanin (tricyclazole and phthalide) and DOPA-melanin (tropolone and kojic acid) pathways on a set of conidial color mutants, we investigated the involvement of melanin biosynthesis in A. flavus conidial pigment formation. Results imply that both pathways have no bearing on conidial pigment biosynthesis of A. flavus.


Early diagnosis of pregnancy in sows by ultrasound evaluation of embryo development and uterine echotexture.
Two operators attempted to detect pregnancy ultrasonographically in 196 sows daily from 15 to 25 days after insemination; 20 unbred sows were also investigated. The probe was applied transcutaneously on the right abdominal wall near the last three mammary glands. During each examination, the embryos were visualised and their transverse and longitudinal dimensions were measured. Pregnancy was confirmed by an ultrasonographic detection of embryos five days after the first ultrasound diagnosis and finally 30 to 32 days after insemination. The accuracy of diagnosis was less than 83 per cent on days 15, 16 and 17 but improved to more than 90 per cent from day 18 onwards. The uterine echotexture was studied in seven sows at oestrus and 15, 17, 19, 21, 23 and 25 days after insemination. The echotexture was more homogeneous from days 15 to 25 after insemination than at oestrus.


Tolbutamide inhibits cAMP-dependent phosphorylation of liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.
The activity of a bifunctional enzyme, liver 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase (F-2,6-Pase), which regulates the level of liver fructose-2,6-bisphosphate (F-2,6-P2), the most potent activator of PFK, is modulated by its phosphorylation rate mainly catalyzed by cAMP-dependent protein kinase A (PKA). To elucidate the action mechanism of sulfonylurea on liver F-2,6-P2 production, effects of tolbutamide on PKA-dependent phosphorylation of purified liver PFK-2/F-2,6-Phase protein and on kinase and phosphatase activities of the purified enzyme were examined in vitro. The purified enzyme was phosphorylated in the presence of the catalytic subunit of PKA, and tolbutamide inhibited the enzyme phosphorylation catalyzed by PKA in a dose-dependent manner. By adding the same dosages of tolbutamide used in the phosphorylation experiment, reduced activity of PFK-2 and increased activity of F-2,6-Pase in the presence of PKA were restored to the levels observed in the absence of PKA. On the other hand, carboxytolbutamide, an inactive metabolite of tolbutamide, had little effect on enzyme phosphorylation and activity. Our results indicate that tolbutamide inhibits a phosphorylation of the liver PFK-2/F-2,6-Pase catalyzed by PKA along with an activation of PFK-2 and an inactivation of F-2,6-Pase, leading to liver F-2,6-P2 production.


[HGH response to dihydroxyphenylalanine (L-dopa) (author's transl)].
L-dopa, administered at dose levels of 250 mg., was used to assess HGH release in 36 children. In five cases of hypopituitary dwarfs no response was obtained and in the remaining 31 cases affected by short stature not of endocrine origin, the highest peak was produced 30' after the test (12.71 +/- 11.61 ng/ml; p less than 0.0005). Significant responses were also obtained at 60' (11.81 +/- 10.47 ng/ml; p less than 0.0005), 90' (7.25 +/- 7.49 ng/ml; p less than 0.0005) and 120' (4.8 +/- 4.86 ng/ml; p less than 0.005).


Rapid and Specific Detection of Apple stem grooving virus by Reverse Transcription-recombinase Polymerase Amplification.
Apple stem grooving virus (ASGV) is considered to cause the most economically important viral disease in pears in Korea. The current PCR-based methods used to diagnose ASGV are time-consuming in terms of target detection. In this study, a novel assay for specific ASGV detection that is based on reverse transcription-recombinase polymerase amplification is described. This assay has been shown to be reproducible and able to detect as little as 4.7 ng/μl of purified RNA obtained from an ASGV-infected plant. The major advantage of this assay is that the reaction for the target virus is completed in 1 min, and amplification only requires an incubation temperature of 42°C. This assay is a promising alternative method for pear breeding programs or virus-free certification laboratories.


3D surface and body documentation in forensic medicine: 3-D/CAD Photogrammetry merged with 3D radiological scanning.
A main goal of forensic medicine is to document and to translate medical findings to a language and/or visualization that is readable and understandable for judicial persons and for medical laymen. Therefore, in addition to classical methods, scientific cutting-edge technologies can and should be used. Through the use of the Forensic, 3-D/CAD-supported Photogrammetric method the documentation of so-called "morphologic fingerprints" has been realized. Forensic, 3-D/CAD-supported Photogrammetry creates morphologic data models of the injury and of the suspected injury-causing instrument allowing the evaluation of a match between the injury and the instrument. In addition to the photogrammetric body surface registration, the radiological documentation provided by a volume scan (i.e., spiral, multi-detector CT, or MRI) registers the sub-surface injury, which is not visible to Photogrammetry. The new, combined method of merging Photogrammetry and Radiology data sets creates the potential to perform many kinds of reconstructions and postprocessing of (patterned) injuries in the realm of forensic medical case work. Using this merging method of colored photogrammetric surface and gray-scale radiological internal documentation, a great step towards a new kind of reality-based, high-tech wound documentation and visualization in forensic medicine is made. The combination of the methods of 3D/CAD Photogrammetry and Radiology has the advantage of being observer-independent, non-subjective, non-invasive, digitally storable over years or decades and even transferable over the web for second opinion.


Regulation of intracellular cyclooxygenase levels by gene transcription and protein degradation.
Cyclooxygenases-1 and -2 (COX-1 and -2) catalyze the committed step in prostaglandin formation. Each isozyme subserves different biological functions. This is, at least in part, a consequence of differences in patterns of COX-1 and COX-2 expression. COX-1 is induced during development, and COX-1 mRNA and COX-1 protein are very stable. These latter properties can explain why COX-1 protein levels usually remain constant in those cells that express this isozyme. COX-2 is usually expressed inducibly in association with cell replication or differentiation. Both COX-2 mRNA and COX-2 protein have short half-lives relative to those of COX-1. Therefore, COX-2 protein is typically present for only a few hours after its synthesis. Here we review and develop the concepts that (a) COX-2 gene transcription can involve at least six different cis-acting promoter elements interacting with trans-acting factors generated by multiple, different signaling pathways, (b) the relative contribution of each cis-acting COX-2 promoter element depends on the cell type, the stimulus and the time following the stimulus and (c) a unique 27 amino acid instability element located just upstream of the C-terminus of COX-2 targets this isoform to the ER-associated degradation system and proteolysis by the cytosolic 26S proteasome.


Foot Surgery Using Resorbable Magnesium Screws.
The use of bioabsorbable magnesium (Mg) screws is new in foot surgery. Their relative merit over conventional titanium screws has not yet been proven. This prospective case series study was conducted to compare the clinical and radiological outcomes of bioabsorbable Mg screws and titanium screws. A consecutive series of patients (n = 60; 11 men and 49 women) underwent corrective hallux valgus surgery. The minimum follow-up period was 1 year. The assessment was based on a patient questionnaire, including the American Orthopedic Foot and Ankle Society (AOFAS) hallux valgus score, visual analog scale, patient's global impression of change (PGIC), and fifth metatarsus circumference (IF5C). The radiographic assessment included the intermetatarsal and hallux valgus angles, as well as time to osteotomy union and hardware failure. At 1 year, similar results were obtained radiographically. The healing of the osteotomies was significantly faster in the Mg group. Hardware failure was common in the Mg group (5/26) than in the TI group (0/34) but hardware removal was more common in the TI group (6/34) versus the MG group (0/26). IF5C increased by 8 ± 2 mm in the Mg group. The AOFAS and PGIC scores at 6 months were similar. Validated foot scores and radiographic analysis indicated that there was no detectable difference between the groups. The fast achievement of osteotomy union compensates for a high rate of hardware failure, resulting in patient satisfaction and avoiding reoperation for hardware removal. Level of Clinical Evidence: 3.


Nanomechanical and Vibrational Signature of Chikungunya Viral Particles.
Chikungunya virus (CHIKV) belongs to the genus Alphaviridae, with a single-stranded positive-sense RNA genome of 11.8 kbp encoding a polyprotein that generates both non-structural proteins and structural proteins. The virus is transmitted by the Aedes aegypti and A. albopictus mosquitoes, depending on the location. CHIKV infection leads to dengue-like musculoskeletal symptoms and has been responsible for several outbreaks worldwide since its discovery in 1952. Patients often experience fever, headache, muscle pain, joint swelling, and skin rashes. However, the ultrastructural and mechanical properties of CHIKV have not been fully characterized. Thus, this study aims to apply a physical approach to investigate CHIKV's ultrastructural morphology and mechanical properties, using atomic force microscopy and Raman spectroscopy as the main tools. Using nanomechanical assays of AFM and a gold nanoparticles substrate for Raman signal enhancement, we explored the conformational plasticity, morphology, vibrational signature, and nanomechanical properties of the chikungunya virus, providing new information on its ultrastructure at the nanoscale and offering a novel understanding of the virus' behavior upon mechanical disruptions besides its molecular composition.


Development of a Recombinase Polymerase Amplification (RPA) assay for acute hepatopancreatic necrosis disease (AHPND) detection in Pacific white shrimp (Penaeus vannamei).
Acute hepatopancreatic necrosis disease (AHPND) is currently the most important bacterial disease of shrimp that has caused enormous losses to the shrimp industry worldwide. The causative agent of AHPND are Vibrio spp. Carrying plasmids containing the pirA and pirB genes which encode binary toxins, PirAB. Currently, AHPND is mostly diagnosed by PCR-based platforms which require the use of sophisticated laboratory instrumentation and are not suitable for a point-of-care diagnostics. Therefore, the availability of an alternative method based on isothermal amplification would be suitable for AHPND detection outside a laboratory setting and extremely useful at a pond side location. Isothermal amplification is based on the nucleic acid amplification at a single temperature and does not require the use of a thermal cycler. In this study, we developed an isothermal Recombinase Polymerase Amplification (RPA) assay for AHPND detection targeting both pirA and pirB genes, simultaneously and evaluated the specificity and sensitivity of the assay. The assay could detect AHPND without any cross-reaction with other microbial pathogens and Specific Pathogen Free (SPF) shrimp. The limit of detection of the assay was 5 copies of pirAB genes. To evaluate the reliability of the assay in detecting AHPND, DNA from Penaeus vannamei shrimp displaying acute and chronic infection were analyzed by the RPA assay and the results were compared with SYBR Green real-time PCR assay. While there was a 100% conformity between the two assay while detecting acute phase infection, RPA appeared to be more sensitive in detecting chronic phase infection. The data suggest that RPA assay described here would be a reliable method in detecting AHPND outside a standard laboratory setting.


Basal cell carcinoma of the perineum.
Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. Most BCCs are found on areas of UV-damaged skin, The study of BCCs of sun-protected regions, however, suggests a more complex pathogenesis. We present a case of BCC of the perineum in a man with no previous history of skin cancer. This is the first report of BCC in this region and one of a small body of cases arising on or near the genital and perianal regions.


Increased urinary TGF-beta1 and cortical renal GLUT1 and GLUT2 levels: additive effects of hypertension and diabetes.
Diabetes and mesangial stretch caused by hypertension increase mesangial matrix deposition which is induced by local production of transforming growth factor beta 1 (TGF-beta1). Both conditions are associated with cortical GLUT1 overexpression. We evaluated the effect of genetically determined hypertension and its association with diabetes on urinary TGF-beta1 and cortical GLUT1 and GLUT2 expression. We studied Wistar-Kyoto rats (controls, C) and spontaneously hypertensive rats (SHR), weighing approximately 210 g, 30 days after the injection of streptozotocin (diabetic, D) or citrate buffer (10 C, 9 SHR, 12 C-D and 15 SHR-D). Twenty-four-hour urine was collected for glucose, albumin, and TGF-beta1 determinations. Catheters were implanted into the femoral artery to measure the arterial blood pressure in conscious animals 1 day later. Then GLUT1 and GLUT2 protein levels (Western blotting) in renal cortex and medulla were evaluated. The cortical GLUT1 levels were 5, 2, and 7 times higher in SHR, C-D, and SHR-D groups versus C group (p < 0.05); the GLUT2 contents were 1.5, 1.8, and 2.3 times higher in SHR, C-D and SHR-D groups versus C group (p < 0.05). The urinary TGF-beta1 level was elevated by diabetes and diabetes and hypertension, but not by hypertension alone: 1.39 +/- 0.2, 2.34 +/- 0.6, 18.2 +/- 3.2, and 28.8 +/- 7.6 ng/24 h, respectively, in C, SHR, C-D, and SHR-D groups (p < 0.05). Diabetes, hypertension, and especially their association increase the renal cortical GLUT1 and GLUT2 levels. The magnitude of GLUT1 overexpression caused by hypertension is higher than that induced by diabetes alone. The impact on urinary TGF-beta1 occurs when diabetes and hypertension are associated, suggesting an effect that is triggered in the presence of GLUT1 overexpression and hyperglycemia.


A rare type of burn injury due to butane gas inhalation.
Abusive inhalation of butane gas is becoming a serious public health problem among teenagers and young adult population; however, there has been little reporting on explosion burns associated with abuse of butane cigarette lighter fluid. Retrospective study was conducted of 22 patients who were burned in last 2 years in explosion of butane gas, a flammable, odorless, and colorless aliphatic hydrocarbon. Details of sociodemographic profile of the patients, any underlying psychiatric illness, alcohol abuse, depth of burn injury, any associated injury, duration of hospitalization, and percentage of burned area were recorded and analyzed. All of the patients were young men, and most had superficial burn injury. Hospital stay ranged from 0 to 11 days. All of the patients were treated with conservative management.


Toxic epidermal necrolysis in a patient treated with gold salts and benoxaprofen.
Fatal toxic epidermal necrolysis is described in a patient, treated concurrently with sodium aurothiomalate and benoxaprofen, who had previously had these two drugs separately, with only minor mucocutaneous problems while on gold, and no adverse effects from benoxaprofen. It is suggested that benoxaprofen could act synergistically with gold, resulting in enhancement of mucocutaneous side-effects, which are common to both these drugs.


Risk Perception and Risk-Taking Behaviour during Adolescence: The Influence of Personality and Gender.
This study investigated the influence of personality characteristics and gender on adolescents' perception of risk and their risk-taking behaviour. Male and female participants (157 females: 116 males, aged 13-20) completed self-report measures on risk perception, risk-taking and personality. Male participants perceived behaviours as less risky, reportedly took more risks, were less sensitive to negative outcomes and less socially anxious than female participants. Path analysis identified a model in which age, behavioural inhibition and impulsiveness directly influenced risk perception, while age, social anxiety, impulsiveness, sensitivity to reward, behavioural inhibition and risk perception itself were directly or indirectly associated with risk-taking behaviour. Age and behavioural inhibition had direct relationships with social anxiety, and reward sensitivity was associated with impulsiveness. The model was representative for the whole sample and male and female groups separately. The observed relationship between age and social anxiety and the influence this may have on risk-taking behaviour could be key for reducing adolescent risk-taking behaviour. Even though adolescents may understand the riskiness of their behaviour and estimate their vulnerability to risk at a similar level to adults, factors such as anxiety regarding social situations, sensitivity to reward and impulsiveness may exert their influence and make these individuals prone to taking risks. If these associations are proven causal, these factors are, and will continue to be, important targets in prevention and intervention efforts.


Simulation-Based Clarification of Appropriate Factors for Presenting Phosphene in Two Directions Avoiding Electrical Interference.
Walking support systems are essential for blind people. In this study, the presentation of phosphene position is focused on as a method to detect obstacles for blind people. When the phosphene is used in a walking support system, it is necessary to accurately present the phosphene in at least three directions of the visual field. Controlling the presentation of phosphene position has been reported in several previous studies. However, methodologies to present phosphene in multiple directions without any electric interference have not as yet been investigated. In this study, therefore, appropriate stimulation factors are clarified by the simulation of electric field on the eyeball surface which is strongly related to the presentation of phosphene position in the visual field. As a result of the simulation, it was revealed that the distance of each electrode does not give a significant effect to the eyeball surface. However, the phase of alternating current significantly changed the electric field on the eyeball surface. From investigation of the simulation results, it was clarified that the transition of the electric field on the eyeball surface can be controlled using anti-phase stimulation. In addition, the methodology to present the phosphene at least in two directions was verified.


Sensorimotor event: an approach to the dynamic, embodied, and embedded nature of sensorimotor cognition.
In this paper, I explore the notion of sensorimotor event as the building block of sensorimotor cognition. A sensorimotor event is presented here as a neurally controlled event that recruits those processes and elements that are necessary to address the demands of the situation in which the individual is involved. The notion of sensorimotor event is intended to subsume the dynamic, embodied, and embedded nature of sensorimotor cognition, in agreement with the satisficing and bricoleur approach to sensorimotor cognition presented elsewhere (Vilarroya, 2012). In particular, the notion of sensorimotor event encompasses those relevant neural processes, but also those bodily and environmental elements, that are necessary to deal with the situation in which the individual is involved. This continuum of neural processes as well as bodily and environmental elements can be characterized, and this characterization is considered the basis for the identification of the particular sensorimotor event. Among other consequences, the notion of sensorimotor event suggests a different approach to the classical account of sensory-input mapping onto a motor output. Instead of characterizing how a neural system responds to an external input, the idea defended here is to characterize how system-in-an-environment responds to its antecedent situation.


Low Incidence of Advanced Neoplasia in Serrated Polyposis Syndrome After (Sub)total Colectomy: Results of a 5-Year International Prospective Cohort Study.
Serrated polyposis syndrome (SPS) is accompanied by a substantially increased colorectal cancer (CRC) risk. To prevent or treat CRC in patients with a very high polyp burden, (sub)total colectomy with ileorectal or ileosigmoidal anastomosis is regularly performed. The CRC risk after (sub)total colectomy might be decreased, but evidence is lacking. We aimed to assess the yield of endoscopic surveillance in patients with SPS who underwent (sub)total colectomy. For this post hoc analysis, we used prospectively collected data from a large international prospective cohort study. We included patients diagnosed with SPS (World Health Organization type I and/or III) who underwent (sub)total colectomy. Primary endpoint was the cumulative 5-year incidence of CRC and advanced neoplasia (AN). Forty-eight patients (mean age 61 [±7.8]; 52% men) were included and followed up for a median of 4.7 years (interquartile range 4.7-5.1). None of the patients developed CRC during follow-up. Five patients developed AN, corresponding to a cumulative 5-year AN incidence of 13% (95% confidence interval 1.2-23). In 4 patients, AN was diagnosed at the first surveillance endoscopy after study inclusion, and in 1 patient, AN was detected during subsequent rounds of surveillance. The risk of AN was similar for patients with ileorectal and ileosigmoidal anastomosis (logrank P = 0.83). (Sub)total colectomy mitigates much of the excess risk of CRC in patients with SPS. Advanced neoplasms are mainly detected at the first endoscopy after (sub)total colectomy. Based on these results, after the first surveillance, intervals might be extended beyond the currently recommended 1-2 years.


Upper limb functional electrical stimulation for walker ambulation in hemiplegia: a case report.
Electrical stimulation has been sporadically used in the treatment of hemiplegia. Reported benefits include decreasing spasticity, providing a supplementary means for range of motion exercises, increasing strength, and improving local blood flow in a paretic or paralyzed limb. Some studies have also shown functional gains in the hemiplegic upper limb following treatment with electrical stimulation. Nevertheless, there have been very few reports of the use of neuromuscular stimulation to achieve new hemiplegic upper limb activity not possible without the electrical stimulation. This is a case report of a head injury patient who was able to begin ambulation with a walker, without physical assistance, for the first time in the 16 yr since his injury. A new electrical stimulation device (Handmaster) initially used therapeutically, and then functionally, provided a reliable, strong grasp and release and was instrumental in achieving the new level of function. The device proved to be easy to use in the home, giving the patient microprocessor-controlled therapeutic and patterned functional electrical stimulation.


Deep Learning-Based Predictive Model for Revascularization of Chronic Total Occlusions on Angiographic Imaging.
Revascularization of chronic total occlusions (CTO) is currently one of the most complex procedures in percutaneous coronary intervention (PCI), requiring the use of specific devices and a high level of experience to obtain good results. Once the clinical indication for extensive ischemia or angina uncontrolled with medical treatment has been established, the decision to perform coronary intervention is not simple, since this procedure has a higher rate of complications than non-PCI percutaneous intervention, higher ionizing radiation doses and a lower success rate. However, CTO revascularization has been shown to be helpful in symptomatic improvement of angina, reduction of ischemic burden, or improvement of ejection fraction. The aim of this work is to determine whether a model developed using deep learning techniques, and trained with angiography images, can better predict the likelihood of a successful revascularization procedure for a patient with a chronic total occlusion (CTO) lesion in their coronary artery (measured as procedure success and the duration of time during which X-ray imaging technology is used to perform a medical procedure) than the scales traditionally used. As a preliminary approach, patients with right coronary artery CTO will be included since they present standard angiographic projections that are performed in all patients and present less technical variability (duration, projection angle, image similarity) among them.The ultimate objective is to develop a predictive model to help the clinician in the decision to intervene and to analyze the performance in terms of predicting the success of the technique for the revascularization of chronic occlusions.Clinical Relevance- The development of a deep learning model based on the angiography images could potentially overcome the gold standard and help interventional cardiologists in the treatment decision for percutaneous coronary intervention, maximizing the success rate of coronary intervention.


Parasite-Probiotic Interactions in the Gut: Bacillus sp. and Enterococcus faecium Regulate Type-2 Inflammatory Responses and Modify the Gut Microbiota of Pigs During Helminth Infection.
Dietary probiotics may enhance gut health by directly competing with pathogenic agents and through immunostimulatory effects. These properties are recognized in the context of bacterial and viral pathogens, but less is known about interactions with eukaryotic pathogens such as parasitic worms (helminths). In this study we investigated whether two probiotic mixtures (comprised of Bacillus amyloliquefaciens, B. subtilis, and Enterococcus faecium [BBE], or Lactobacillus rhamnosus LGG and Bifidobacterium animalis subspecies Lactis Bb12 [LB]) could modulate helminth infection kinetics as well as the gut microbiome and intestinal immune responses in pigs infected with the nodular worm Oesophagostomum dentatum. We observed that neither probiotic mixture influenced helminth infection levels. BBE, and to a lesser extent LB, changed the alpha- and beta-diversity indices of the colon and fecal microbiota, notably including an enrichment of fecal Bifidobacterium spp. by BBE. However, these effects were muted by concurrent O. dentatum infection. BBE (but not LB) significantly attenuated the O. dentatum-induced upregulation of genes involved in type-2 inflammation and restored normal lymphocyte ratios in the ileo-caecal lymph nodes that were altered by infection. Moreover, inflammatory cytokine release from blood mononuclear cells and intestinal lymphocytes was diminished by BBE. Collectively, our data suggest that selected probiotic mixtures can play a role in maintaining immune homeostasis during type 2-biased inflammation. In addition, potentially beneficial changes in the microbiome induced by dietary probiotics may be counteracted by helminths, highlighting the complex inter-relationships that potentially exist between probiotic bacteria and intestinal parasites.


[Contractile reactions of the small intestine induced by stimulation of beta-adrenoreceptors].
Isopropylnoradrenaline (1-2 micrograms/ml-1) induced contractile responses of the jejunum and ileum. The contractions could occur practically simultaneously with the onset of responses of arterial vessels or their latency period (reaching up to 33 sec). Blockade of M-cholinoreceptors with atropine (0.2-0.4 mg/kg) prevented both response types whereas blockade of alpha-adrenoreceptors with phentolamine (1 mg/kg) augmented them. Preliminary infusion of acetylcholine in subthreshold concentration (10(-5)-10(-6) g/ml; 1 ml/min) into the small intestine vascular bed considerably augmented the responses to isopropylnoradrenaline. The data obtained corroborate existence of presynaptic activating beta-adrenoreceptors localized on a cholinergic neuron, in the small intestine.


Subtle Effects of Aliphatic Alcohol Structure on Water Extraction and Solute Aggregation in Biphasic Water/n-Dodecane.
Organic phase aggregation behavior of 1-octanol and its structural isomer, 2-ethylhexanol, in a biphasic n-dodecane-water system is studied with a combination of physical measurement, small-angle X-ray scattering (SAXS), and atomistic molecular dynamic simulations. Physical properties of the organic phases are probed following their mixing and equilibration with immiscible water phases. Studies reveal that the interfacial tension decreases as a function of increasing alcohol concentration over the solubility range of the alcohol with no evidence for a critical aggregate concentration (cac). An uptake of water into the organic phases is quantified, as a function of alcohol content, by Karl Fischer titrations. The extraction of water into dodecane was further assessed as a function of alcohol concentration via the slope-analysis method sometimes employed in chemical separations. This method provides a qualitative understanding of solute (water/alcohol) aggregation in the organic phase. The physical results are supported by analyses of SAXS data that reveals an emergence of aggregates in n-dodecane at elevated alcohol concentrations. The observed aggregate structure is dependent on the alcohol tail group geometry, consistent with surfactant packing parameter. The formation of these aggregates is discussed at a molecular level, where alcohol-alcohol and alcohol-water H-bonding interactions likely dominate the occurrence and morphology of the aggregates.


Cognitive fluctuations in Lewy body dementia: towards a pathophysiological framework.
Fluctuating cognition is a complex and disabling symptom that is seen most frequently in the context of Lewy body dementias encompassing dementia with Lewy bodies and Parkinson's disease dementia. In fact, since their description over three decades ago, cognitive fluctuations have remained a core diagnostic feature of dementia with Lewy bodies, the second most common dementia in the elderly. In the absence of reliable biomarkers for Lewy body pathology, the inclusion of such patients in therapeutic trials depends on the accurate identification of such core clinical features. Yet despite their diagnostic relevance, cognitive fluctuations remain poorly understood, in part due to the lack of a cohesive clinical and scientific explanation of the phenomenon itself. Motivated by this challenge, the present review examines the history, clinical phenomenology and assessment of cognitive fluctuations in the Lewy body dementias. Based on these data, the key neuropsychological, neurophysiological and neuroimaging correlates of cognitive fluctuations are described and integrated into a novel testable heuristic framework from which new insights may be gained.


A monoclonal antibody against meningococcus group B polysaccharides distinguishes embryonic from adult N-CAM.
The neural cell adhesion molecules (N-CAM) occur chiefly in two molecular forms that are selectively expressed at various stages of development. Highly sialylated forms prevalent in embryonic and neonatal brain are gradually replaced by less sialylated forms as development proceeds. Here we describe a monoclonal antibody raised against the capsular polysaccharides of meningococcus group B (Men B) which specifically distinguishes embryonic N-CAM from adult N-CAM. This antibody recognizes alpha 2-8-linked N-acetylneuraminic acid units (NeuAc alpha 2-8). Immunoblot together with immunoprecipitation experiments with cell lines or tissue extracts showed that N-CAM are the major glycoproteins bearing such polysialosyl units. Moreover we could not detect any sialoglycolipid reactive with this antibody in mouse brain or in the neural cell lines examined. By indirect immunofluorescence staining this anti-Men B antibody decorated cells such as AtT20 (D16/16), which expressed the embryonic forms of N-CAM, but not cells that expressed the adult forms. In primary cultures this antibody allowed us to follow the embryonic-to-adult conversion in individual cells. In addition, the existence of cross-reactive polysialosyl structures on Men B and N-CAM in embryonic brain cells for caution in efforts to develop immunotherapy against neonatal meningitis.


Enhanced efficiency of thin film solar cells using a shifted dual grating plasmonic structure.
We propose an ultrathin solar cell architecture design which incorporates two periodic layers of metallic and dielectric gratings. Both layers couple the incident light to photonic and plasmonic modes, thus increasing absorption within the cell. The relative position between the two gratings is examined, and is shown to have significant impact on absorption. A lateral shift between the two layers introduces structural asymmetry, and enables coupling of the incident field to optically dark photonic modes. Furthermore, the lateral shift influences mode interactions. Current density enhancement is calculated under AM1.5 G solar illumination, and is found to reach a value of 1.86. The structure proposed is optimized and compared to solar cells with a single layer of metallic or dielectric nanostructures.


Preparation and evaluation of polymer based microcarriers for all-trans-retinoic acid.
Polymeric biomaterials are being investigated for the last several years because of their controllable properties. In this study, it was aimed to prepare and evaluate the atRA carrying system using Poly(lactide-co-glycolide) (PLGA). Microparticles were characterized in terms of morphology and encapsulation efficiency. Release studies were performed for the evaluation of drug release rates. Cytotoxicity tests were implemented on MCF-7 Human breast cancer cell line for the investigation of drug and polymer toxicity. The microparticles were found smooth and spherical in shape. However, as the loaded drug amount increased, the sizes of microparticles also increased and the size distribution became less uniform. The sizes of atRA-loaded microparticles ranged between 1-10 µm. The encapsulation efficiency of atRetinoic acid (all-trans-Retinoic acid) was achieved approximately %90. Approximately, 45% of atRA was released from atRA-loaded microparticles by the end of 4-5 days. Cell growth inhibition was observed after 4 days of incubation of cells with PLGA microparticles.


Case 305.
A 27-year-old man was admitted to the emergency department with fever and thoracic pain. In the previous 6 months, the patient lost a substantial amount of weight (12 kg). His family history was negative for cardiac disease. Electrocardiography revealed sinus rhythm, and diffuse T-wave inversion. Two-dimensional echocardiography was performed (Fig 1) and revealed normal left systolic function (ejection fraction, 60%). Laboratory tests showed elevated levels of high-sensitivity cardiac troponin (1.07 ng/mL; normal value, <0.015 ng/mL), high levels of C-reactive protein (16 mg/dL; normal range, 0-5 mg/dL), and leukocytosis with an eosinophilia level of 8710/μL (normal level, <400/μL). Parasitic and infectious diseases (Toxocara canis, strongyloides, filariasis, cysticercosis, fasciola, trichinella, echinococcosis) were excluded based on blood and fecal test results. Corticosteroid therapy was started, and the patient was dismissed. A few days later, he was readmitted to the emergency department with a headache and suddenly blurred vision. Neurologic and ophthalmologic findings were normal, and MRI of the brain was performed (Fig 2). Cardiac MRI (Fig 3) was performed 2 days later and revealed the following quantitative results: (a) left ventricular end-diastolic volume (LVDV) of 165 mL (LVDV/body surface area [BSA], 89 mL/m2; normal range, 64-100 mL/m2), left ventricular end-systolic volume (LVSV) of 80 mL (LVSV/BSA, 43 mL/m2; normal range, 17-39 mL/m2); stroke volume (SV) of 85 mL (SV/BSA, 46 mL/m2; normal range, 43-67 mL/m2); and ejection fraction of 52% and (b) right ventricular end-diastolic volume (RVDV) of 163 mL (RVDV/BSA, 88 mL/m2; normal range, 63-111 mL/m2), right ventricular end-systolic volume (RVSV) of 81 mL (RVSV/BSA, 44 mL/m2; normal range, 32-92 mL/m2); stroke volume (SV) of 82 mL (SV/BSA, 44 mL/m2; normal range, 39-71 mL/m2); and ejection fraction of 50%.


[Primary glomerulopathies: incidence, dynamics and clinical manifestations of morphological variants].
4400 biopsies studied in the pathology department of I.M. Sechenov Moscow Medical Academy in 1970-1999 were analysed. Primary glomerulopathy (PGP) was found in 62.4% of nephrobiopsies. PGP was represented by mesangioproliferative glomerulonephritis (MPGN, 48.9%), mesangiocapillary glomerulonephritis (MCGN, 18.4%), membranous nephropathy (MN, 13.4%), focal segmentary glomerulosclerosis/hyalinosis (FSGH, 7.8%), minimal changes (MC, 5.6%). Mainly of nephrotic origin were MC, MN, FSGH. The hematuric form was primarily represented by MPGN. In 1970-1999, the share of non-inflammatory variants (MC, MN, FSGN) was increasing while hematuric variants (MPGN, MCGN) had the tendency to a decrease in their relative frequency.


Intent-to-treat analysis for longitudinal studies with drop-outs.
We consider intent-to-treat (IT) analysis of clinical trials involving longitudinal data subject to drop-out. Common methods, such as Last Observation Carried Forward imputation or incomplete-data methods based on models that assume random dropout, have serious drawbacks in the IT setting. We propose a method that involves multiple imputation of the missing values following drop-out based on an "as treated" model, using actual dose after drop-out if this is known, or imputed doses that incorporate a variety of plausible alternative assumptions if unknown. The multiply-imputed data sets are then analyzed using IT methods, were subjects are classified by randomization group rather than by the dose actually received. Results from the multiply-imputed data sets are combined using the methods of Rubin (1987, Multiple Imputation for Nonresponse in Surveys). A novel feature of the proposed method is that the models for imputation differ from the model used for the analysis of the filled-in data. The method is applied to data on a clinical trial for Tacrine in the treatment of Alzheimer's disease.


Chimeric potyvirus-like particles as vaccine carriers.
Presentation of subunit vaccines in a highly ordered aggregate form can result in enhanced immune responses. Coat protein (CP) monomers of a potyvirus (Johnsongrass mosaic virus) when produced in heterologous host expression systems (Escherichia coli, yeast and insect cells) self-polymerized to produce potyvirus-like particles (PVLPs). The N- and C-terminal regions of potyvirus CP are surface-exposed and are not required for assembly. Hybrid CP monomers containing short peptides fused to their N- and/or C-termini, or large target antigens fused to the N-terminus or replacing most of the N- or C-terminal exposed regions retained the ability to assemble into hybrid PVLPs. Such chimeric PVLPs were highly immunogenic in mice and rabbits even in the absence of any adjuvant. Potyvirus CP is highly versatile in accommodating peptides or large antigens and is able to present antigens exposed on the surface of virus-like particles. This, combined with the efficiency of high level bacterial and insect cell expression systems, makes PVLPs an attractive non-pathogenic and non-replicative vaccine carrier.


In vitro activity of hepatitis B virus polymerase: requirement for distinct metal ions and the viral epsilon stem-loop.
Hepadnaviruses have a complex replication cycle which includes reverse transcription of the pregenomic RNA. The initial step in this process in hepatitis B virus (HBV) requires the viral polymerase to engage a highly stable region of secondary structure within the pregenomic RNA termed the epsilon stem-loop. While reverse transcriptases belonging to the retrovirus family use a specific cellular tRNA as primer, HBV polymerase utilizes a tyrosine residue located within its own N terminus. Therefore, the first deoxyribonucleotide is covalently coupled to HBV polymerase prior to extension of the DNA strand by conventional reverse transcription. We have expressed HBV polymerase in a baculovirus and following purification have found it to be active with respect to protein-priming and reverse transcription of copurified RNA. Importantly, we found both of these processes to be critically dependent on the presence of the epsilon stem-loop. The metal ion preferences of HBV polymerase were also investigated for both the protein-priming and reverse transcription activities of this enzyme. Reverse transcription was dependent on magnesium, with an optimal concentration of 5 mM. However, protein-priming was strongly favoured by manganese ions and was optimal at a concentration of 1 mM. Thus, using manganese as sole source of metal ions our activity assay is restricted to the protein-priming event and will allow the search for novel antivirals specifically blocking this unique mechanism.


Low bacterial diet versus control diet to prevent infection in cancer patients treated with chemotherapy causing episodes of neutropenia.
Neutropenia is a potentially serious side effect of chemotherapy and a major risk factor for infection, which can be life-threatening. It has been hypothesised that a low bacterial diet (LBD) can prevent infection and (infection-related) mortality in cancer patients receiving chemotherapy that causes episodes of neutropenia, but much remains unclear. This review is an update of a previously published Cochrane review. The primary objective of this review was to determine the efficacy of an LBD versus a control diet in preventing infection and in decreasing (infection-related) mortality in adult and paediatric cancer patients receiving chemotherapy that causes episodes of neutropenia. Secondary objectives were to assess time to first febrile episode, need for empirical antibiotic therapy, diet acceptability and quality of life. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 4), the Database of Abstracts of Reviews of Effects (DARE) (2015, Issue 4), PubMed (from 1946 to 4 May 2015), EMBASE (from 1980 to 4 May 2015) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1981 to 4 May 2015).In addition, we searched the reference lists of relevant articles and conference proceedings of American Society of Hematology (ASH; from 2000 to 2015), European Bone Marrow Transplantation (EBMT; from 2000 to 2015), Oncology Nurses Society (ONS; from 2000 to 2015), International Society for Paediatric Oncology (SIOP; from 2000 to 2014), Multinational Association of Supportive Care in Cancer (MASCC; from 2000 to 2015), American Society of Clinical Oncology (ASCO; from 2000 to 2015), Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC; from 2000 to 2015), European Society for Clinical Nutrition and Metabolism (ESPEN; from 2000 to 2015), American Society for Parenteral and Enteral Nutrition (ASPEN; from 2000 to 2015) and European Hematology Association (EHA; from 2000 to 2015). In May 2015, we scanned the National Institutes of Health Register via clinicaltrials.gov and the International Standard Randomised Controlled Trial Number (ISRCTN) Register (www.controlled-trials.com). Randomised controlled trials (RCTs) comparing use of an LBD versus a control diet with regard to infection rate, (infection-related) mortality, time to first febrile episode, need for empirical antibiotic therapy, diet acceptability and quality of life in adult and paediatric cancer patients receiving chemotherapy causing episodes of neutropenia. Two review authors independently performed study selection, 'Risk of bias' assessment and data extraction. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. In the original version of this review, we identified three RCTs that assessed different intervention and control diets in 192 participants (97 randomised to intervention diet; 95 to control diet) with different types of malignancies. For the update, we identified no eligible new studies. Co-interventions (e.g. protective environment, antimicrobial prophylaxis, central venous catheter care, oral care, hygiene practices, colony-stimulating factors) and outcome definitions also differed between studies. In all included studies, it was standard policy to give empirical antibiotics (and sometimes also antimycotics) to (some of) the participants diagnosed with an infection. Two studies included adults and one study included children. In all studies, only a scant description of treatment regimens was provided. All studies had methodological limitations. Pooling of results of included studies was not possible. In two individual studies, no statistically significant differences in infection rate were identified between intervention and control diets; another study showed no significant differences between treatment groups in the number of chemotherapy cycles with an infection. None of the studies mentioned infection-related mortality, but in one study, no significant difference in overall survival was observed between treatment groups. Time from onset of neutropenia to fever, duration of empirical antibiotics and antimycotics, diet acceptability (i.e. following the diet easily and following the diet throughout all chemotherapy cycles) and quality of life were all evaluated by only one study; for all outcomes, no statistically significant differences between treatment arms were identified. At the moment, no evidence from individual RCTs in children and adults with different malignancies underscores use of an LBD for prevention of infection and related outcomes. All studies differed with regard to co-interventions, outcome definitions and intervention and control diets. As pooling of results was not possible, and as all studies had serious methodological limitations, we could reach no definitive conclusions. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. On the basis of currently available evidence, we are not able to provide recommendations for clinical practice. Additional high-quality research is needed.


Drinking at European universities? A review of students' alcohol use.
High volumes of alcohol consumption and risky single occasion drinking (RSOD) among university students have been shown to be associated with considerable harm to both those who consume alcohol and their fellow students. The vast majority of these studies are based on US and Canadian samples. The present article provides an overview of the characteristics of alcohol-consuming university students in Europe. 65 relevant articles published within the last 20years using European student populations could be identified. Sociodemographic, individual, social, and university-related characteristics associated with alcohol consumption patterns could be identified. Male students, in particular, tended to consume alcohol more often and in higher quantities, including RSOD. Students consumed alcohol chiefly during social gatherings and for social and enhancement motives. Those without family obligations and those living alone, with roommates or in areas with a high density of students were more likely to consume alcohol in higher quantities, and to engage in RSOD. Students tend to overestimate the extent of their fellow students' alcohol consumption. Health promotion and prevention efforts which focus on these characteristics (i.e., gender, drinking motives, living conditions and social norms), and which have been successful and evaluated among university students in the US and Canada, may also be very promising for their European counterparts.


Women in Allergy and Immunology: The Future Is Female, Let Us Soar!
Despite increases in the number of female physicians in the past 50 years, women remain underrepresented in key areas of medicine, such as practice owners and partners, professional society leaders, principal investigators, full professors, chairs, and deans. Women are paid less, oftentimes for more work. Allergy and Immunology (AI), as a specialty, lacks substantial workforce research, but trends across specialties are consistent. We review what is currently known about women in AI and consider barriers to practice, advancement, and contribution. Through a new inquiry, we find that the challenges women in AI encounter can be summarized through 6 themes: work-life balance, professional advancement, salary equity, mentorship and sponsorship, bias, and sexual harassment and misconduct. Together, we must address these challenges head-on and provide an equitable environment for women in AI to thrive, especially those affected by intersectionality. To do so, we suggest targeted, tangible actions to promote opportunities, offer institutional support, and advance reporting and culture change outlets across AI settings.


Feedback stabilizes propagation of synchronous spiking in cortical neural networks.
Precisely timed action potentials related to stimuli and behavior have been observed in the cerebral cortex. However, information carried by the precise spike timing has to propagate through many cortical areas, and noise could disrupt millisecond precision during the transmission. Previous studies have demonstrated that only strong stimuli that evoke a large number of spikes with small dispersion of spike times can propagate through multilayer networks without degrading the temporal precision. Here we show that feedback projections can increase the number of spikes in spike volleys without degrading their temporal precision. Feedback also increased the range of spike volleys that can propagate through multilayer networks. Our work suggests that feedback projections could be responsible for the reliable propagation of information encoded in spike times through cortex, and thus could serve as an attentional mechanism to regulate the flow of information in the cortex. Feedback projections may also participate in generating spike synchronization that is engaged in cognitive behaviors by the same mechanisms described here for spike propagation.


Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type 1 Diabetic Mice.
Hypertriglyceridemia is considered to be driven by increased lipolysis in type 1 diabetes mellitus (T1DM). However, information regarding the transcriptional circuitry that governs lipolysis remains incomplete in T1DM. Protein arginine methyltransferase 4 (PRMT4), a transcriptional coactivation factor, promotes autophagy and may play an important role in lipolysis. We wonder whether activated lipolysis in T1DM is regulated by PRMT4. Recombinant adeno-associated virus was adopted to overexpress PRMT4 in adipose tissue of mice. Streptozotocin (150 mg/kg) was injected intraperitoneally into mice to induce T1DM. Plasma insulin, triglycerides, free fatty acids (FFAs) levels were determined using commercial assay kits. Differentiated adipocytes were applied to verify the regulation of PRMT4 on lipolysis. Elevated serum triglycerides and FFAs were observed in PRMT4-overexpressed T1DM mice. We also observed that PRMT4 over-expression induced the decrease of fat pads weights and adipocyte sizes. Moreover, expression levels of lipolysis-related molecules, including ATGL, HSL, and MAGL, and HSL phosphorylation levels were increased in PRMT4-overexpressed mice when compared to those of control mice. In vitro, PRMT4 promoted FFAs release and activated HSL phosphorylation, whereas PRMT4 knockdown inhibited these processes. PRMT4 promotes lipolysis and increases serum triglyceride in T1DM.


Facile reduction of arsenate in methanogenic sludge.
Due to the recent enactment of a stricter drinking water standard for arsenate, large quantities of arsenate-laden drinking water residuals will be disposed in municipal landfills. The objective of this study was to determine the role of methanogenic consortia on the conversion of arsenate. Methanogenic conditions commonly occur in mature municipal solid waste landfills. The results indicate the rapid and facile reduction of arsenate to arsenite in methanogenic sludge. Endogenous substrates in the sludge were sufficient to support the reductive biotransformation. However the rates of arsenate reduction were stimulated by the addition of exogenous electron donating substrates, such as H2, lactate or a mixture of volatile fatty acids. A selective methanogenic inhibitor stimulated arsenate reduction in microcosms supplied with H2, suggesting that methanogens competed with arsenate reducers for the electron donor. Rates of arsenate reduction increased with arsenate concentration up to 2 mM, higher concentrations were inhibitory. The electron shuttle, anthraquinone-2,6-disulfonate, used as a model of humic quinone moieties, was shown to significantly increase rates of arsenate reduction at substoichiometric concentrations. The presence of sulfur compounds, sulfate and sulfide, did not affect the rate of arsenate transformation but lowered the yield of soluble arsenite, due to the precipitation of arsenite with sulfides. The results taken as a whole suggest that arsenate disposed into anaerobic environments may readily be converted to arsenite increasing the mobility of arsenic. The extent of the increased mobility will depend on the concentration of sulfides generated from sulfate reduction.


Enhancing site-specific DNA integration by a Cas9 nuclease fused with a DNA donor-binding domain.
The CRISPR/Cas system is widely used for genome editing. However, robust and targeted insertion of a DNA segment remains a challenge. Here, we present a fusion nuclease (Cas9-N57) to enhance site-specific DNA integration via a fused DNA binding domain of Sleeping Beauty transposase to tether the DNA segment to the Cas9/sgRNA complex. The insertion was unidirectional and specific, and DNA fragments up to 12 kb in length were successfully integrated. As a test of the system, Cas9-N57 mediated the insertion of a CD19-specific chimeric antigen receptor (CD19-CAR) cassette into the AAVS1 locus in human T cells, and induced intrahepatic cholangiocarcinoma in mice by simultaneously mediating the insertion of oncogenic KrasG12D into the Rosa26 locus and disrupting Trp53 and Pten. Moreover, the nuclease-N57 fusion proteins based on AsCpf1 (AsCas12a) and CjCas9 exhibited similar activity. These findings demonstrate that CRISPR-associated nuclease-N57 protein fusion is a powerful tool for targeted DNA insertion and holds great potential for gene therapy applications.


Toxicities associated with NBOMe ingestion-a novel class of potent hallucinogens: a review of the literature.
A new class of synthetic hallucinogens called NBOMe has emerged as drugs of abuse. Our aim was to conduct a systematic review of published reports of toxicities associated with NBOMe ingestion. We searched PubMed for relevant English-language citations that described adverse effects from analytically confirmed human NBOMe ingestion. Demographic and clinical data were extracted. A total of 10 citations met the criteria for inclusion, representing 20 individual patients. 25I-NBOMe was the most common analogue identified, followed by 25B-NBOMe and 25C-NBOMe. Fatalities were reported in 3 (15%) cases. Of all the patients, 7 (35%) were discharged after a period of observation, whereas 8 (40.0%) required admission to an intensive care unit. The most common adverse effects were agitation (85.0%), tachycardia (85.0%), and hypertension (65.0%). Seizures were reported in 8 (40.0%) patients. The most common abnormalities reported on laboratory tests were elevated level of creatinine kinase (45.0%), leukocytosis (25.0%), and hyperglycemia (20.0%). NBOMe ingestion is associated with severe adverse effects. Clinicians need to have a high index of suspicion for NBOMe ingestion in patients reporting the recent use of hallucinogens.


Water Splitting Exceeding 17% Solar-to-Hydrogen Conversion Efficiency Using Solution-Processed Ni-Based Electrocatalysts and Perovskite/Si Tandem Solar Cell.
Various noble metal-free electrocatalysts have been explored to enhance the overall water splitting efficiency. Ni-based compounds have attracted substantial attention for achieving efficient oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) catalysts. Here, we show superior electrocatalysts based on NiFe alloy electroformed by a roll-to-roll process. NiFe (oxy)hydroxide synthesized by an anodization method for the OER catalyst shows an overpotential of 250 mV at 10 mA cm-2, which is dramatically smaller than that of bare NiFe alloy with an overpotential of 380 mV at 10 mA cm-2. Electrodeposited NiMo films for the HER catalyst also exhibit a small overpotential of 100 mV at 10 mA cm-2 compared with that of bare NiFe alloy (550 mV at 10 mA cm-2). A combined spectroscopic and electrochemical analysis reveals a clear relationship between the surface chemistry of NiFe (oxy)hydroxide and the water splitting properties. These outstanding fully solution-processed catalysts facilitate superb overall water splitting properties due to enlarged active surfaces and highly active catalytic properties. We combined a solution-processed monolithic perovskite/Si tandem solar cell with MAPb(I0.85Br0.15)3 for the direct conversion of solar energy into hydrogen energy, leading to the high solar-to-hydrogen efficiency of 17.52%. Based on the cost-effective solution processes, our photovoltaic-electrocatalysis (PV-EC) system has advantages over latest high-performance solar water splitting systems.


Interactive effects between radiation and other factors on cancer risk among A-bomb survivors--an overview of RERF studies.
This paper reviews RERF cancer studies conducted to examine interactive effects between radiation and epidemiological risk factors, including smoking habits, occupation, dietary habits and OB/GYN history. Special emphasis is placed on a review of studies of interactive effects between cigarette smoking and radiation on lung cancer risk. Comments on these studies are made and proposals for future studies are presented.


Adolescent predictors and environmental correlates of young adult alcohol use problems.
To examine the rates of young adult alcohol and drug use and alcohol problems, adolescent predictors of young adult alcohol problems and correlations with young adult social, work and recreational environments. Adolescents were followed longitudinally into young adulthood. Predictors were measured in grade 9 (average age 15), and environmental correlates and outcomes in young adulthood (average age 21). Students recruited in Victoria, Australia in 2002, were resurveyed in 2010/11. Analytical n=2309, 80% retention. Adolescent self-report predictors included past-month alcohol use. Young adults completed the Alcohol Use Disorders Identification Test (AUDIT) together with reports of environmental influences. Comparisons to United States national school graduate samples revealed higher rates of alcohol, tobacco and illicit drug use (other than cannabis) in Victoria. For example, rates of past month use at age 21-22 were: alcohol 69.3% US versus 84.9%, 95% confidence interval (CI) 81.3-88.6% Victoria; illicit drugs (other than cannabis) 8.8 versus 12.7%, CI 9.7-15.7%. AUDIT alcohol problems (scored 8+) were identified for 41.2%, CI 38.8-43.6% of young adults in Victoria. The likelihood of young adult alcohol problems was higher for frequent adolescent alcohol users and those exposed to environments characterized by high alcohol use and problems in young adulthood. High rates of alcohol problems are evident in more than two in five Australian young adults, and these problems appear to be influenced both by earlier patterns of adolescent alcohol use and by young adult social, work and recreational environments.


The binding of fucose-containing glycoproteins by hepatic lectins. The binding specificity of the rat liver fucose lectin.
The parameters that affect the interaction of ligands with a fucose-binding lectin from rat liver have been examined. 125I-Fucosyl-bovine serum albumin (Fuc-BSA) containing 50 residues of fucose/molecule was used as the standard ligand. At low initial concentrations of ligand (10 ng/ml) and lectin (140 ng/ml), the reaction reaches equilibrium at pH 7.8, 23 degrees C, within 40 min. The binding of ligands is Ca2+ dependent with half-maximal binding occurring at 54 microM Ca2+; of several metal ions tested, only Sr2+ partially replaced Ca2+. Binding was maximal between pH 7.6 and 8.6, fell slightly up to pH 10, but fell markedly below pH 7. The lectin-ligand complexes dissociated at low pH, on removal of Ca2+, or in the presence of a large excess of competing ligand. The apparent association constant (Ka) for Fuc-BSA was 1.75 X 10(8) M-1. The fucose content of the Fuc-BSA also influenced binding, with little apparent binding below 24 fucose residues/molecule and maximal binding from 40 to 50 fucose residues/molecule. With knowledge of the parameters influencing binding, sensitive reproducible assays for the lectin were developed. The binding specificity of the lectin was examined by measuring the inhibition of 125I-Fuc-BSA binding by neoglycoproteins, monosaccharides, and glycosides or by direct binding of neoglycoproteins. Galactosides and beta-linked fucosides were the best ligands among the neoglycoproteins, with much weaker binding by mannosyl- or N-acetylglucosaminyl-BSA. On the basis of the pattern of inhibition of Fuc-BSA binding by various monosaccharides and glycosides, it is possible to propose the conformations of saccharides that best fit the lectin-binding site. The C1 conformation of N-acetyl-D-galactosamine fits best, although other not obviously related monosaccharides such as L-fucose, L-arabinose, and D-mannose can also assume conformations that permit them to be effective inhibitors. The pattern of binding of neoglycoproteins to the lectin differs from that of other pure hepatic lectins. Thus, the fucose lectin has a high affinity for Fuc-BSA and galactosyl-BSA but a low affinity for N-acetylglucosaminyl-BSA. The galactose lectin binds only galactosyl-BSA and shows little binding with either N-acetylglucosaminyl-BSA or Fuc-BSA. In contrast, the mannose/N-acetylglucosamine lectin binds N-acetylglucosaminyl-BSA and Fuc-BSA but not galactosyl-BSA.


Tumor necrosis factor receptor associated factor-4: an adapter protein overexpressed in metastatic prostate cancer is regulated by microRNA-29a.
The tumor necrosis factor receptor (TNFR)-associated factor 4 (TRAF4) is a member of TRAF family proteins that act as major signal transducers of the TNF receptor and the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) superfamily. TRAF4 has been reported to be overexpressed in various human cancers. However, the exact mechanisms that regulate the expression of TRAF4 still remain elusive. The objective of the present study was to investigate the regulatory mechanism of TRAF4 expression in prostate cancer. We initially identified microRNA-29a (miR‑29a) as a possible candidate to bind TRAF4 3' untranslated region (3'UTR) by the algorithm, TargetScan. The expression of TRAF4 mRNA and protein was inversely associated with miR-29a expression in prostate cancer cell lines (LNCaP, DU145 and PC3). TRAF4 expression was reduced by the introduction of mimic miR-29a in LNCaP cells. Luciferase activity from the construct harboring wild-type TRAF4 3'UTR was reduced by the mimic miR-29a and this reduction was diminished by introducing mutations at the predicted miR-29a binding site. On the other hand, TRAF4 was upregulated when transfected with the inhibitor of miR-29a in DU145 and PC3 cells. TRAF4 was significantly upregulated in patients with metastatic prostate cancer compared to those with localized prostate cancer. Furthermore, there was a significant inverse correlation between TRAF4 and miR-29a expression in tumor tissues from radical prostatectomy. Considered together, our results suggest that the tumor suppressor microRNA, miR-29a, is one of the regulators of TRAF4 expression in metastatic prostate cancer.


Identification of proteins and mRNAs in isolated yellow crescents of ascidian eggs.
The yellow crescent or myoplasm is a localized cytoplasmic region in eggs of the ascidian Styela that is partitioned to the larval tail muscle and mesenchyme cells during embryonic development. To determine whether the myoplasm contains a specific subset of maternal macromolecules, its abundant proteins and mRNAs were identified and compared to those present in the remainder of the egg. This was accomplished by exploiting a newly developed method for the mass fractionation of yellow crescents which is based on the presence of a unique cytoskeletal domain in the yellow crescent region. The fractionation yields a yellow crescent fraction (YCF) representing the myoplasm and a supernatant fraction representing the nonmyoplasmic regions. The YCF comprises structures which contain the characteristic myoplasmic organelles and about 10% of the protein, 8% of the RNA, and 1-3% of the poly(A) of whole eggs. Two-dimensional gel electrophoresis indicated that the YCF contains 15 polypeptides that are undetectable in the supernatant fraction and 43 polypeptides that are significantly depleted in the latter fraction. The proteins restricted to the YCF are both of cytoskeletal and noncytoskeletal origin. In vitro translation of RNA in a message-dependent lysate and analysis of [35S]methionine-labelled polypeptide products by two-dimensional gel electrophoresis did not reveal qualitative differences between the YCF and the supernatant fraction. Furthermore, the mRNAs coding for two polypeptides that were localized in the myoplasm were not restricted to the YCF. The results suggest that qualitative differences in proteins but not in prevalent mRNAs exist between the yellow crescent and the other cytoplasmic regions of Styela eggs.


Quantification and sensory studies of character impact odorants of different soybean lecithins.
Fifty-four potent odorants in standardized, hydrolyzed, and deoiled and hydrolyzed soybean lecithins were quantified by high-resolution gas chromatography/mass spectrometry (HRGC/MS). The characterization of their aroma impact was performed by calculation of nasal (n) and retronasal (r) odor activity values (OAVs). For this, the nasal and retronasal recognition thresholds of 18 odor-active compounds were determined in vegetable oil. The following compounds showed the highest nOAVs: 2,3-diethyl-5-methylpyrazine, methylpropanal, acetic acid, pentanoic acid, 2-ethyl-3,5-dimethylpyrazine, pentylpyridine, (Z)-1,5-octadien-3-one, 2-methylbutanal, and beta-damascenone. In addition to the compounds above, 1-octen-3-one, 1-nonen-3-one, and 3-methyl-2,4-nonandione showed potent rOAVs. The results of quantification and OAV calculation were confirmed by a model mixture of 25 impact odorants, which yielded a highly similar sensory profile to that of the original soybean lecithin. The sensory importance of pyrazines and free acids increased through enzymatic hydrolysis and decreased by the process of deoiling. The impact of unsaturated ketones on the lecithin aroma was not changed by either process.


Revisiting Wittgenstein's puzzle: hierarchical encoding and comparison facilitate learning of probabilistic relational categories.
Kittur et al. (2004, 2006) and Jung and Hummel (2011, 2014) showed that people have great difficulty learning relation-based categories with a probabilistic (i.e., family resemblance) structure, in which no single relation is shared by all members of a category. Yet acquisition of such categories is not strictly impossible: in all these studies, roughly half the participants eventually learned to criterion. What are these participants doing that the other half are not? We hypothesized that successful participants were those who divided the nominal categories into two or more sub-categories, each of which individually had a deterministic structure. We report three experiments testing this hypothesis: explicitly presenting participants with hierarchical (category and sub-category) structures facilitated the acquisition of otherwise probabilistic relational categories, but only when participants learned the subordinate-level (i.e., deterministic) categories prior to learning the nominal (i.e., probabilistic) categories and only when they were permitted to view multiple exemplars of the same category simultaneously. These findings suggest that one way to learn natural relational categories with a probabilistic structure [e.g., Wittgenstein's (1953), category game, or even mother] is by learning deterministic subordinate-level concepts first and connecting them together under a common concept or label. They also add to the literature suggesting that comparison of multiple exemplars plays an instrumental role in relational learning.


Pedometer- and accelerometer-based exercise in subjects with diabetes mellitus.
Pedometers and accelerometers have recently become applicable for not only monitoring but increasing level of physical activity (PA). We summarize the effects of pedometer- and accelerometer-based exercise interventions on glucose metabolism in subjects with diabetes mellitus (DM). We searched intervention studies that investigated the effects of step-defined exercise interventions using pedometers and accelerometers on the levels of glucose metabolism markers, such as plasma glucose and hemoglobin A1c (HbA1c), in adult subjects with type 2 DM. The study characteristics and findings of glucose metabolism markers were reviewed. Of 16 eligible studies reviewed, significant improvements in glucose metabolism markers were found in the intervention group compared to that observed in the control group in six studies: the HbA1c level in four studies, both the HbA1c and plasma glucose levels in one study and continuous glucose monitoring in one study. Four of these six studies emphasized a significance of PA intensity in addition to PA amount. Five studies found a significant increase in the number of steps, but only one of these studies showed significant reductions in glucose metabolism markers. No studies demonstrated a dose-response relationship between changes in the number of steps and glucose metabolism markers. Limited studies showed significant improvements in glucose metabolism markers and steps among subjects with type 2 DM. Future studies are needed regarding how to use pedometers and accelerometers to achieve improvements in glucose metabolism with increases in PA in such subjects, especially more focus on PA intensity.


Enhanced and Selective Absorption of Molybdenum Nanostructured Surfaces for Concentrated Solar Energy Applications.
Surfaces of commercial molybdenum (Mo) plates have been textured by fs-laser treatments with the aim to form low-cost and efficient solar absorbers and substrates for thermionic cathodes in Concentrated Solar Power conversion devices. Morphological (SEM and AFM), optical (spectrophotometry), and structural (Raman spectroscopy) properties of the samples treated at different laser fluences (from 1.8 to 14 J/cm2) have been characterized after the laser treatments and also following long thermal annealing for simulating the operating conditions of thermionic converters. A significant improvement of the solar absorptance and selectivity, with a maximum value of about four times higher than the pristine sample at a temperature of 800 K, has been detected for sample surfaces treated at intermediate fluences. The effects observed have been related to the light trapping capability of the laser-induced nanotexturing, whereas a low selectivity, together with a high absorptance, could be revealed when the highest laser fluence was employed due to a significant presence of oxide species. The ageing process confirms the performance improvement shown when treated samples are used as solar absorbers, even though, due to chemical modification occurring at the surface, a decrease of the solar absorptance takes place. Interestingly, the sample showing the highest quantity of oxides preserves more efficiently the laser texturing. The observation of this behaviour allows to extend the applicability of the laser treatments since, by further nanostructuring of the Mo oxides, it could be beneficial also for sensing applications.


[Combined endovascular stent implantation and coil embolization for the treatment of a vertebro-basilar fusiform aneurysm: technical case report].
We describe a case of the combined application of endovascular stent implantation and Guglielmi detachable coil packing for the treatment of a vertebro-basilar fusiform aneurysm and review the literature on stent placement to treat cerebral aneurysms. A 70-year-old female presented with an acute headache from subarachnoid hemorrhage. A fusiform aneurysm with a broad-based neck and dome, measuring 15 mm, involving the union of the vertebral arteries and the proximal basilar artery was demonstrated on cerebral angiography. The aneurysm was judged to be inoperable and treated conservatively. Twelve days later the patient was transferred to our hospital for endovascular therapy. An intravascular stent (MultiLink) was placed across the base of the aneurysm through the right vertebral artery. After this, coil placement in the aneurysm around the stent was performed via a microcatheter guided from the left vertebral artery. After that a microcatheter was guided from the right vertebral artery through the interstices of the stent into the aneurysm, and additional coils were placed. Final angiography showed subtotal occlusion of the aneurysm and excellent blood flow of the parent artery through the stent. There were no new neurological deficits. Neither rerupture nor ischemic event has occurred. The use of stents provides another treatment for managing the difficult entity of intracranial aneurysms.


Transcriptional regulators of hepatic gluconeogenesis.
Glucose is a primary fuel for generating energy in basic daily activities. Thus, glucose homeostasis is tightly regulated by counter-regulatory hormones such as glucagon, cortisol, and insulin, which affect key organs including liver, skeletal muscle, pancreas, and adipocytes. Among metabolic tissues, liver plays a critical role in controlling glucose production under various hormonal and metabolic cues. Under fasting, acute activation of both glycogenolysis and gluconeogenesis is achieved by post-translational modification or allosteric activation of key rate-limiting enzymes, thereby enabling enhanced glucose production from the liver to maintain glucose homeostasis. More prolonged fasting or starvation leads to the chronic activation of gluconeogenesis that requires increased expression of key enzymes in the pathway, which is turned off under feeding conditions by the molecular events that are initiated by insulin. This process is normally achieved by the regulation of gene expression at the level of transcription. Recently, the transcriptional regulators of hepatic gluconeogenesis are considered as potential therapeutic targets for the treatment of type 2 diabetes. In this review, we would like to discuss the current knowledge regarding the key transcriptional activators and inhibitors of hepatic gluconeogenic program to provide the better insight into the control of glycemia in the disease status.


Cost-effectiveness analysis of antiretroviral therapy in a cohort of HIV-infected patients starting first-line highly active antiretroviral therapy during 6 years of observation.
Costs may play a role in deciding how and when to start highly active antiretroviral therapy (HAART) in a naïve patient. The aim of the present study was to assess the cost- effectiveness of treatment with HAART in a large clinical cohort of naïve adults to determine the potential role of single-tablet regimens in the management of patients with human immunodeficiency virus (HIV). An incremental cost-effectiveness ratio analysis was performed, including a quality-adjusted life year approach. In total, 741 patients (females comprising 25.5%) were retrospectively included. The mean age was 39 years, the mean CD4 cell count was 266 cells/μL, and the mean viral load was 192,821 copies/mL. The most commonly used backbone was tenofovir + emtricitabine (77.6%); zidovudine + lamivudine was used in 10%, lamivudine + abacavir in 3%, and other nucleoside reverse transcriptase inhibitor (NRTI) or NRTI-free regimens in 9.4% of patients. NNRTIs were used in 52.8% of cases, boosted protease inhibitors in 44.1%, and unboosted protease inhibitors and integrase inhibitors in 0.7% and 2.4%, respectively. Starting therapy at CD4 >500 cells/μL and CD4 351-500 cells/μL rather than at <201 cells/μL was the more cost-effective approach. The same consideration was not true comparing current indications with the possibility to start HAART at any CD4 value (eg, >500 cells per μL); in this case, the incremental cost-effectiveness ratio value was €199,130 per quality-adjusted life year gained, a higher value than the one suggested in guidelines. The single-tablet regimen (STR) invariably dominated any other therapeutic approach. Sensitivity analysis was performed, and starting right away with an STR was cost-effective even when compared with therapeutic strategies contemplating STR as simplification. By integrating clinical data with economic variables, our study offers an estimate of the cost-effectiveness of the various first-line treatment strategies for patients infected with HIV and provides significant evidence to be used in future prospective pharmacoeconomic evaluations.


Eye movements and psychiatric disease.
During the past year a number of studies have been published on eye movement dysfunction in patients with psychiatric disease. According to the mainstream of modern neuropsychiatric research, these studies cover either genetic aspects or the results of pharmacological manipulation. A few studies addressed impaired smooth pursuit eye movements (eye tracking dysfunction) in unaffected relatives of psychiatric patients, and were important in excluding non-specific effects (e.g. medication) and isolating genetic predisposition to the disease. This predisposition could be demonstrated in families of schizophrenic patients irrespective of whether the index case was sporadic or familial. One large study demonstrated pathological distributions of various parameters of smooth pursuit eye movement performance in groups of schizophrenic patients and their relatives. However, another study challenged the specificity of eye tracking dysfunction as a trait marker for schizophrenia by showing that its prevalence was identical among relatives of patients with affective disorder and schizophrenia. Eye tracking dysfunction was associated with two gene polymorphisms that interfere with dopamine metabolism and are thus reasonable candidate genes for the predisposition to schizophrenia. The influence of nicotine and neuroleptic drugs on eye movement performance was studied in schizophrenic patients. Nicotine improved smooth pursuit performance in three studies, one of which attributed this finding to enhanced attention. Two groups of schizophrenic patients treated with two different atypical neuroleptic drugs, risperidone and olanzapine, did not differ in a battery of saccadic tasks. Eye movements provide an important tool to measure pharmacological effects in patients and unravel genetic traits in psychiatric disease.


Assessing the therapeutic efficacy of VEGFR-1-targeted polymer drug conjugates in mouse tumor models.
Polymer-drug conjugates that can actively target the tumor vasculature have emerged as an attractive technology for improving the therapeutic efficacy of cytotoxic drugs. We have recently provided, for the first time, in vivo evidence showing the significant advantage of the E-selectin-targeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin conjugate, P-(Esbp)-DOX, in inhibiting primary tumor growth and preventing the formation and development of cancer metastases. Here, we describe the design of a vascular endothelial growth factor receptor (VEGFR)-1-targeted HPMA copolymer-DOX conjugate (P-(F56)-DOX) that can actively and simultaneously target different cell types in the tumor microenvironment, such as endothelial cells (ECs), bone marrow-derived cells and many human cancer cells of diverse tumor origin. The VEGFR-1-targeted copolymer was tested for its binding, internalization and in vitro cytotoxicity in ECs (bEnd.3 and cEND cells) and cancer cells (B16-F10, 3LL and HT29). The in vivo anti-cancer activity of P-(F56)-DOX was then tested in two tumor-bearing mice (TBM) models (i.e., primary Lewis lung carcinoma (3LL) tumors and B16-F10 melanoma pulmonary metastases), relative to that of the E-selectin-targeted system (P-(Esbp)-DOX) that solely targets ECs. Our results indicate that the binding and internalization profiles of the VEGFR-1-targeted copolymer were superior towards ECs as compared to cancer cells and correlated well to the level of VEGFR-1 expression in cells. Accordingly, the VEGFR-1-targeted copolymer (P-(F56)-DOX) was more toxic towards bEnd.3 cells than to cancer cells, and exhibited significantly higher cytotoxicity than did the non-targeted control copolymer. P-(F56)-DOX inhibited 3LL tumor growth and significantly prolonged the survival of mice with B16-F10 pulmonary metastases. When compared to a system that actively targets only tumor vascular ECs, P-(F56)-DOX and P-(Esbp)-DOX exhibited comparable efficacy in slowing the growth of primary 3LL tumors and prolonging the survival of these mice. Still, P-(Esbp)-DOX had more pronounced anti-tumor activity in mice bearing B16-F10 lung metastases after a single intravenous injection, at an equivalent DOX dose. Overall, our results indicate that the VEGFR-1- and E-selectin-targeted drug delivery systems evaluated here show enhanced anti-cancer activity, and prolonged the survival of mice after a single intravenous injection. This is thus the first study comparing the anti-tumor activity of VEGFR-1- and E-selectin-targeted polymer drug conjugates in the same TBM models at an equivalent drug dose.


Socio-cultural, psychosexual and biomedical factors associated with genital symptoms experienced by men in rural India.
Biomedical, anthropological and psychiatric frameworks have been used to research different elements of men's sexual health - sexually transmitted infections, psychosexual concerns and psychological distress - but rarely within the same study. We combined these in a study in rural north India. In Tehri Garhwal and Agra districts, we explored male perceptions of genital and sexual symptoms through focus group discussions and then conducted a clinic-based survey of 366 symptomatic men who presented at rural private provider clinics. Men's urine specimens were tested for gonorrhoea and chlamydia infection using polymerase chain reaction techniques. Researchers screened them for probable psychological distress by administering the General Health Questionnaire (12- items). Results revealed that local and traditional notions of health influenced men's symptom perceptions, with semen loss their predominant concern. Dhat, commonly perceived as an involuntary semen loss, corresponded most closely with the symptom of urethral discharge, but was attributed mainly to non-infectious causes. It could also manifest as a syndrome with physical weakness and mental lethargy. FGD participants lacked correct and complete information on reproductive health. Around 75% of the symptomatic men presented with dhat, but only 5.5% tested positive for gonorrhoea or chlamydia. Application of syndromic sexually transmitted infection (STI) guidelines in these settings could result in over diagnosis and over treatment with antibiotics. In contrast, there was a significant association between dhat and probable psychological distress as detected by the GHQ (Adjusted OR, GHQ case positive: 2.66, 95% CI: 1.51-4.68). Our study confirms the existence of a dhat syndrome in rural India, which is culturally influenced and reflects heightened psychosexual concerns as well as mental distress states. Comprehensive health services for men should include assessments of their psychosexual needs and be supported by reproductive/sexual health education. STI treatment guidelines for urethral symptoms should be revised and be based on epidemiological data.


Long-range antiferromagnetic order in malonate-based compounds Na2M(H2C3O4)2·2H2O (M = Mn, Fe, Co, Ni).
The recently discovered metal-malonate compounds of formulae Na2M(H2C3O4)2·2H2O with M = Mn, Fe, Co, Ni are investigated for their magnetic properties. While the Cu-based material is a weak ferromagnet, all other members present antiferromagnetic interactions. Neutron powder diffraction experiments reveal the establishment of a long range magnetic order at low temperature in the Pbca Shubnikov magnetic group. The magnetic structures are characterized by antiferromagnetic layers perpendicular to [001]. These layers are stacked antiparallel (M = Fe) or parallel (M = Mn, Ni) in the (a, c) plane. Magnetic moments are collinear to b for the former and to c for the latter. The M = Co malonate exhibits a non-collinear magnetic structure intermediate between the two latter, with components along b and c. Density functional theory calculations indicate that the dominant magnetic interaction, J1, occurs along a malonate group via a carboxylate and links two transition metals within the same layer, while other interactions (inter- or intra-layer) are much weaker, so that these compounds present the dominant characteristics of 2D-antiferromagnets.


Toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation.
Toll-like receptor 4 (TLR4) activation is pivotal to innate immunity and has been shown to regulate proliferation and differentiation of human neural stem cells (hNSCs) in vivo. Here we study the role of TLR4 in regulating hNSC derived from the human telencephalic-diencephalic area of the fetal brain and cultured in vitro as neurospheres in compliance with Good Manifacture Procedures (GMP) guidelines. Similar batches have been used in recent clinical trials in ALS patients. We found that TLR2 and 4 are expressed in hNSCs as well as CD14 and MD-2 co-receptors, and TLR4 expression is downregulated upon differentiation. Activation of TLR4 signaling by lipopolysaccharide (LPS) has a positive effect on proliferation and/or survival while the inverse is observed with TLR4 inhibition by a synthetic antagonist. TLR4 activation promotes neuronal and oligodendrocyte differentiation and/or survival while TLR4 inhibition leads to increased apoptosis. Consistently, endogenous expression of TLR4 is retained by hNSC surviving after transplantation in ALS rats or immunocompromised mice, thus irrespectively of the neuroinflammatory environment. The characterization of downstream signaling of TLR4 in hNSCs has suggested some activation of the inflammasome pathway. This study suggests TLR4 signaling as essential for hNSC self-renewal and as a novel target for the study of neurogenetic mechanisms.


Subdividing the functional psychoses: a family hereditary approach.
Family genetic data, based on standardized and independent diagnostic procedures of index and secondary cases, confirmed the dichotomy between schizophrenias and affective disorders. The classical schizophrenic subtypes exhibited a significant tendency towards homotypia among their secondary cases. The genetic evidence did not support the monopolar-bipolar subdivision of affective disorder. Schizo-affective disorders impinged on the clear-cut schizophrenic and affective psychotic disorders and there was no homotypical tendency among the relatives of index cases with this diagnosis.


Laparoscopic radical gastrectomy for gastric cancer: Long-term outcome in a teaching center.
Laparoscopic gastrectomy for gastric cancer (GC) are increasing, yet the evidence of the relationship between the learning curve and long-term outcomes is limited. To analyze the relationship between the learning curve and survival in GC patients over a 10-year period. This retrospective cohort study studied 3674 patients who underwent laparoscopic radical gastrectomy for gastric cancer. Cusum and Cox regression analysis were used to assess the association between the surgeon's experience and the 3 years overall survival (OS). The 3-year OS of all patients was 71.8 %. This increase of 3-year OS was associated with laparoscopic cases (r = 0.638, p = 0.047). Analysis of the CUSUM curve showed a significant change in the 3-year OS of 1400 cases. Further propensity score matching (PSM) of patients during and after the learning curve (<1400 and ≥ 1400 cases) showed a significant difference in the 3-year OS between the two groups (68.5 % vs. 72.3 %, p = 0.045). Cox regression analysis verified that in ≥1400 cases, prior laparoscopic surgery (p = 0.045), textbook outcome (TO) and the number of retrieved lymph nodes (LNs) were independent protective factors. The LN non-compliance rate was an independent risk factor. In contrast, the rate of TO and the median number of retrieved LNs were significantly higher after the learning curve (≥1400 cases). Furthermore, the rates of LN non-compliance were significantly lower (p < 0.05). Increasing laparoscopic surgical experience is associated with surgical quality and prognostic improvement in patients with gastric cancer. But improvements in outcomes accrued slowly over a long period.


Lack of modifying potential of 8-methoxypsoralen in the promotion or progression stages of lung carcinogenesis in A/J female mice.
Pretreatment with 8-methoxypsoralen (8-MOP), a potent human CYP2A6 inhibitor, strongly suppresses lung tumorigenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice. Since it has been reported that CYP2A protein is highly expressed in NNK-induced lung adenomas and adenocarcinomas, potential anticancer properties of 8-MOP in female A/J mice were examined subsequent to initiation. The agent was administered at 100 ppm levels in the diet during the promotion phase (experimental weeks 1-16) and progression phase (experimental weeks 16-32) and mice were sacrificed for histopathological examination of lung tumor development at 16 and 32 weeks after the initiation of NNK treatment (2 mg/0.1 ml saline/mouse, i.p.), respectively. Chemopreventive effects of 8-MOP were not observed in either experiment. In addition, no modifying effects on hepatic mRNA levels for CYP2A5, considered to be the mouse ortholog of human CYP2A6, were evident. On immunohistochemical analysis, the CYP2A protein was found to be overexpressed in all lung adenomas and adenocarcinomas, with or without 8-MOP. It can be concluded from the present data that 8-MOP at 100 ppm in the diet does not prevent mouse lung carcinogenesis when administered in the post-initiation phase.


A preliminary study of the neuroprotective role of citicoline eye drops in glaucomatous optic neuropathy.
To study the neuroprotective effect of topical citicoline. Experimental phase to evaluate the ability of citicoline eye drops to reach the vitreous and the retina: The right eyes of 5 mice CD1 were treated with two drops per day for three days of citicoline 1% and 2% (OMK1, Omikron Italia s.r.l.), and then the vitreous was analyzed with the liquid chromatography and spectrometry mass (LC-MS/MS). Clinical phase to determine if topical citicoline is able to delay glaucoma progression, considering perimetric parameters and electro functional tests. Patients were randomized in two groups, OMK1 and OAG. The first group was treated with OMK1 three times per day, plus hypotensive therapy for two months and one month of wash out. The second group was treated only with hypotensive treatment for three months. LC-MS/MS detected the molecule very well, and only OMK1 showed systemic absorption. Thirty-four patients were enrolled, 16 in the OMK1 and 18 in the OAG group. Perimetric parameters showed a positive trend in individual eyes of patients in OMK1 group, but these values were not statistically significant in the whole group. Retinal ganglion cells function improved as shown by reduced P50 latency (P = 0.04) and increased P50-N95 amplitude (P < 0.0001) of pattern electroretinogram, up to 30 days after the washout (P = 0.01; P = 0.002). Visual evoked potential and retino-cortical time improvement regressed after 30 days of washout. In OAG group, there was any change during the follow-up. No adverse reactions were reported in both groups. Topical citicoline seems to have a neuroprotective action.


Interaction of Sindbis virus non-structural protein 3 with poly(ADP-ribose) polymerase 1 in neuronal cells.
The alphavirus non-structural protein 3 (nsP3) has a conserved N-terminal macro domain and a variable highly phosphorylated C-terminal domain. nsP3 forms complexes with cellular proteins, but its role in virus replication is poorly understood and protein interaction domains have not been defined. As the N-terminal macro domain can bind poly(ADP-ribose) (PAR), and PAR polymerase-1 (PARP-1) is activated and autoribosylated during Sindbis virus (SINV) infection, it was hypothesized that PARP-1 and nsP3 may interact. Co-immunoprecipitation studies showed that PARP-1 interacted with nsP3 during SINV infection of NSC34 neuronal cells and was most abundantly present in replication complexes that contained plus- and minus-strand SINV RNAs 10-14 h after infection, prior to PARP-1 activation or automodification with PAR. Treatment with an inhibitor of PARP enzymic activity did not affect the interaction between nsP3 and PARP-1 or SINV replication. Co-expression of individual domains of nsP3 with PARP-1 showed that nsP3 interacted with PARP-1 through the C-terminal domain, not the N-terminal macro domain, and that phosphorylation was not required. It was concluded that PARP-1 interacts with the C-terminal domain of nsP3, is present in replication complexes during virus amplification and may play a role in regulating virus RNA synthesis in neuronal cells.