Tobacco Control Measures to Reduce Socioeconomic Inequality in Smoking: The Necessity, Time-Course Perspective, and Future Implications

Previous systematic reviews of population-level tobacco control interventions and their effects on smoking inequality by socioeconomic factors concluded that tobacco taxation reduce smoking inequality by income (although this is not consistent for other socioeconomic factors, such as education). Inconsistent results have been reported for socioeconomic differences, especially for other tobacco control measures, such as smoke-free policies and anti-tobacco media campaigns. To understand smoking inequality itself and to develop strategies to reduce smoking inequality, knowledge of the underlying principles or mechanisms of the inequality over a long time-course may be important. For example, the inverse equity hypothesis recognizes that inequality may evolve in stages. New population-based interventions are initially primarily accessed by the affluent and well-educated, so there is an initial increase in socioeconomic inequality (early stage). These inequalities narrow when the deprived population can access the intervention after the affluent have gained maximum benefit (late stage). Following this hypothesis, all tobacco control measures may have the potential to reduce smoking inequality, if they continue for a long term, covering and reaching all socioeconomic subgroups. Re-evaluation of the impact of the interventions on smoking inequality using a long time-course perspective may lead to a favorable next step in equity effectiveness. Tackling socioeconomic inequality in smoking may be a key public health target for the reduction of inequality in health

DC superconducting quantum interference devices fabricated using bicrystal grain boundary junctions in Co-doped BaFe2As2 epitaxial films

DC superconducting quantum interference devices (dc-SQUIDs) were fabricated in Co-doped BaFe2As2 epitaxial films on (La, Sr)(Al, Ta)O3 bicrystal substrates with 30deg misorientation angles. The 18 x 8 micro-meter^2 SQUID loop with an estimated inductance of 13 pH contained two 3 micro-meter wide grain boundary junctions. The voltage-flux characteristics clearly exhibited periodic modulations with deltaV = 1.4 micro-volt at 14 K, while the intrinsic flux noise of dc-SQUIDs was 7.8 x 10^-5 fai0/Hz^1/2 above 20 Hz. The rather high flux noise is mainly attributed to the small voltage modulation depth which results from the superconductor-normal metal-superconductor junction nature of the bicrystal grain boundary

An Efficient Ligation Method in the Making of an in vitro Virus for in vitro Protein Evolution

The “in vitro virus” is a molecular construct to perform evolutionary protein engineering. The “virion (=viral particle)” (mRNA-peptide fusion), is made by bonding a nascent protein with its coding mRNA via puromycin in a test tube for in vitro translation. In this work, the puromycin-linker was attached to mRNA using the Y-ligation, which was a method of two single-strands ligation at the end of a double-stranded stem to make a stem-loop structure. This reaction gave a yield of about 95%. We compared the Y-ligation with two other ligation reactions and showed that the Y-ligation gave the best productivity. An efficient amplification of the in vitro virus with this “viral genome” was demonstrated

Nicastrin Functions as a γ-Secretase-Substrate Receptor

Summaryγ-secretase catalyzes the intramembrane cleavage of amyloid precursor protein (APP) and Notch after their extracellular domains are shed by site-specific proteolysis. Nicastrin is an essential glycoprotein component of the γ-secretase complex but has no known function. We now show that the ectodomain of nicastrin binds the new amino terminus that is generated upon proteolysis of the extracellular APP and Notch domains, thereby recruiting the APP and Notch substrates into the γ-secretase complex. Chemical- or antibody-mediated blocking of the free amino terminus, addition of purified nicastrin ectodomain, or mutations in the ectodomain markedly reduce the binding and cleavage of substrate by γ-secretase. These results indicate that nicastrin is a receptor for the amino-terminal stubs that are generated by ectodomain shedding of type I transmembrane proteins. Our data are consistent with a model where nicastrin presents these substrates to γ-secretase and thereby facilitates their cleavage via intramembrane proteolysis

Aortic valve replacement in a young patient with essential thrombocytosis

Essential Thrombocythcythaemia (ET) is an uncommon type of myeloproliferative disorder, characterised by both thrombotic and haemorrhagic diathesis. No clear guidelines exist for the pre- and post-operative management of patients undergoing cardiac surgery in the haematological and surgical literature. This condition has profound implications in patients undergoing cardiac surgery with the use of cardiopulmonary bypass, where heparin is used for anti-coagulation. This dilemma is further compounded in the setting of a young patient undergoing aortic valve replacement (AVR), where insertion of a mechanical prosthesis would be the procedure of choice. This would require life-long anticoagulation with warfarin which can predispose these patients to catastrophic bleeding. Using a tissue valve will subject the patient to multiple redo operations in the patient's lifetime. We report a young patient with ET requiring AVR and discuss the dilemmas surrounding the choice of prosthesis in this patient

Hippocampus, Amygdala and Basal Ganglia Based Navigation Control

In this paper we present a novel robot navigation system aimed at testing hypotheses about the roles of key brain areas in foraging behavior of rats. The key components of the control network are: 1. a Hippocampus inspired module for spatial localization based on associations between sensory inputs and places; 2. an Amygdala inspired module for the association of values with places and sensory stimuli; 3. a Basal Ganglia inspired module for the selection of actions based on the evaluated sensory inputs. By implementing this Hippocampus-Amygdala-Basal Ganglia based control network with a simulated rat embodiment we intend to test not only our understanding of the individual brain areas but especially the interaction between them. Understanding the neural circuits that allows rats to efficiently forage for food will also help to improve the ability of robots to autonomously evaluate and select navigation targets

Choroid plexus tumours

Choroid plexus tumours are rare epithelial brain tumours and limited information is available regarding their biology and the best treatment. A meta-analysis was done to determine prognostic factors and the influence of various treatment modalities. A thorough review of the medical literature (1966–1998) revealed 566 well-documented choroid plexus tumours. These were entered into a database, which was analysed to determine prognostic factors and treatment modalities. Most patients with a supratentorial tumour were children, while the most common sites in adults were the fourth ventricle and the cerebellar pontine angle. Cerebellar pontine angle tumours were more frequently benign. Histology was the most important prognostic factor, as one, five, and 10-year projected survival rates were 90, 81, and 77% in choroid plexus-papilloma (n=353) compared to only 71, 41, and 35% in choroid plexus-carcinoma respectively (P<0.0005). Surgery was prognostically relevant for both choroid plexus-papilloma (P=0.0005) and choroid plexus-carcinoma (P=0.0001). Radiotherapy was associated with significantly better survival in choroid plexus-carcinomas. Eight of 22 documented choroid plexus-carcinomas responded to chemotherapy. Relapse after primary treatment was a poor prognostic factor in choroid plexus-carcinoma patients but not in choroid plexus-papilloma patients. Treatment of choroid plexus tumours should start with radical surgical resection. This should be followed by adjuvant treatment in case of choroid plexus-carcinoma, and a ‘wait and see’ approach in choroid plexus-papilloma

Autism spectrum disorder is related to endoplasmic reticulum stress induced by mutations in the synaptic cell adhesion molecule, CADM1

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unknown molecular pathogenesis. A recent molecular focus has been the mutated neuroligin 3, neuroligin 3(R451C), in gain-of-function studies and for its role in induced impairment of synaptic function, but endoplasmic reticulum (ER) stress induced by mutated molecules also deserves investigation. We previously found two missense mutations, H246N and Y251S, in the gene-encoding synaptic cell adhesion molecule-1 (CADM1) in ASD patients, including cleavage of the mutated CADM1 and its intracellular accumulation. In this study, we found that the mutated CADM1 showed slightly reduced homophilic interactions in vitro but that most of its interactions persist. The mutated CADM1 also showed morphological abnormalities, including shorter dendrites, and impaired synaptogenesis in neurons. Wild-type CADM1 was partly localized to the ER of C2C5 cells, whereas mutated CADM1 mainly accumulated in the ER despite different sensitivities toward 4-phenyl butyric acid with chemical chaperone activity and rapamycin with promotion activity for degradation of the aggregated protein. Modeling analysis suggested a direct relationship between the mutations and the conformation alteration. Both mutated CADM1 and neuroligin 3(R451C) induced upregulation of C/EBP-homologous protein (CHOP), an ER stress marker, suggesting that in addition to the trafficking impairment, this CHOP upregulation may also be involved in ASD pathogenesis