XPC protects against smoking- and carcinogen-induced lung adenocarcinoma

Cigarette smoke (CS) contains hundreds of carcinogens and is a potent inducer of oxidative and bulky DNA damage, which when insufficiently repaired leads to activation of DNA damage response and possibly mutations. The DNA repair protein xeroderma pigmentosum group C (XPC) is primed to play an important role in CS-induced DNA damage because of its function in initiating repair of both bulky oxidative DNA damage. We hypothesized that loss of XPC function will increase susceptibility to developing CS- and carcinogen-induced lung cancer through impaired repair of oxidative DNA damage. Mice deficient in XPC (XPC-/-) exposed to chronic CS developed lung tumors whereas their wild-type littermates (XPC+/+) did not. XPC-/- mice treated with the CS-carcinogen urethane developed lung adenocarcinomas representing progressive stages of tumor development, with lung tumor number increased 17-fold compared with XPC+/+ mice. Mice heterozygous for XPC (XPC+/-) demonstrated a gene-dose effect, developing an intermediate number of lung tumors with urethane treatment. Treatment of XPC-/- mice with the carcinogen 3-methylcholanthrene followed by the proliferative agent butylated hydroxytoluene resulted in a 2-fold increase in lung adenocarcinoma development. Finally, tumor number decreased 7-fold in the lungs of XPC-/- mice by concurrent treatment with the antioxidant, N-acetylcysteine. Altogether, this supports a mechanism by which decreased XPC expression promotes lung adenocarcinoma development in response to CS-carcinogen exposure, due in part to impaired oxidative DNA damage repair

Is Month of Birth a Risk Factor for Colorectal Cancer?

Introduction. The developmental origins of health and disease hypothesis and season of birth have been linked to a wide variety of later life conditions including cancer. Whether any relationship between month and season of birth and colorectal cancer exists is unknown. Methods. A case-control study was performed with month of birth extracted from a dedicated colorectal cancer database. Age and gender matched patients were used as a control group. Generalised linear models were fitted with Poisson and negative binomial responses and logarithmic links. A forward stepwise approach was followed adding seasonal components with 6- and 12-month periods. Results. 1019 colorectal cancer patients and 1277 randomly selected age and gender matched controls were included. For both men and women there is an excess of colorectal cancer in those born in autumn and a corresponding reduction of risk among those born in spring (p = 0.026). For the identified September peak, the excess risk for colorectal cancer was 14.8% (95% CI 5.6–32.3%) larger than the spring trough. Conclusion. There is a seasonal effect in the monthly birth rates of people who are operated for colorectal cancer with a disproportionate excess of cancer in those born in September. Further large studies are required to validate these findings

Blood-Stage Parasitaemia and Age Determine Plasmodium falciparum and P. vivax Gametocytaemia in Papua New Guinea

A better understanding of human-to-mosquito transmission is crucial to control malaria. In order to assess factors associated with gametocyte carriage, 2083 samples were collected in a cross-sectional survey in Papua New Guinea. Plasmodium species were detected by light microscopy and qPCR and gametocytes by detection of pfs25 and pvs25 mRNA transcripts by reverse-transcriptase PCR (qRT-PCR). The parasite prevalence by PCR was 18.5% for Plasmodium falciparum and 13.0% for P. vivax. 52.5% of all infections were submicroscopic. Gametocytes were detected in 60% of P. falciparum-positive and 51% of P. vivax-positive samples. Each 10-fold increase in parasite density led to a 1.8-fold and 3.3-fold increase in the odds of carrying P. falciparum and P. vivax gametocytes. Thus the proportion of gametocyte positive and gametocyte densities was highest in young children carrying high asexual parasite densities and in symptomatic individuals. Dilution series of gametocytes allowed absolute quantification of gametocyte densities by qRT-PCR and showed that pvs25 expression is 10-20 fold lower than pfs25 expression. Between 2006 and 2010 parasite prevalence in the study site has decreased by half. 90% of the remaining infections were asymptomatic and likely constitute an important reservoir of transmission. However, mean gametocyte densities were low (approx. 1-2 gametocyte/muL) and it remains to be determined to what extent low-density gametocyte positive individuals are infective to mosquitos

Stability of trions in strongly spin-polarized two-dimensional electron gases

Low-temperature magneto-photoluminescence studies of negatively charged excitons (X- trions) are reported for n-type modulation-doped ZnSe/Zn(Cd,Mn)Se quantum wells over a wide range of Fermi energy and spin-splitting. The magnetic composition is chosen such that these magnetic two-dimensional electron gases (2DEGs) are highly spin-polarized even at low magnetic fields, throughout the entire range of electron densities studied (5e10 to 6.5e11 cm^-2). This spin polarization has a pronounced effect on the formation and energy of X-, with the striking result that the trion ionization energy (the energy separating X- from the neutral exciton) follows the temperature- and magnetic field-tunable Fermi energy. The large Zeeman energy destabilizes X- at the nu=1 quantum limit, beyond which a new PL peak appears and persists to 60 Tesla, suggesting the formation of spin-triplet charged excitons.Comment: 5 pages (RevTex), 4 embedded EPS figs. Submitted to PRB-R

Life-saving automated external defibrillation in a teenager: a case report

<p>Abstract</p> <p>Background</p> <p>Adolescent sudden death during sport participation is commonly due to cardiac causes. Survival is more likely when an automated external defibrillator (AED) is used soon after collapse.</p> <p>Case presentation</p> <p>We describe a case of sudden death in a 14 year old boy with two remarkable points, successful resuscitation at school using an AED and diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). Bystander cardiopulmonary resuscitation (CPR) was immediately started by a witness and 5 minutes after the event the child was placed on an AED monitor that determined he was in a non shockable rhythm, therefore CPR was continued. Two minutes later, the AED monitor detected a shockable rhythm and recommended a shock, which was then administered. One minute after the shock, a palpable pulse was detected and the child began to breathe by himself. Four days after cardiac arrest, the boy was conversing and self-caring. Cardiac magnetic resonance imaging was suggestive of ARVC.</p> <p>Conclusion</p> <p>Ventricular fibrillation secondary to ARVC may be a devastating event and places young patients and athletes at high risk of sudden death. Immediate CPR and AED have been demonstrated to be lifesaving in such events. Therefore, we suggest that schools should have teachers skilled in CPR and accessible AEDs.</p

Assessment of ultra-sensitive malaria diagnosis versus standard molecular diagnostics for malaria elimination : an in-depth molecular community cross-sectional study

Submicroscopic malaria infections contribute to transmission in exposed populations but their extent is underestimated even by standard molecular diagnostics. Sophisticated sampling and ultra-sensitive molecular methods can maximise test sensitivity but are not feasible in routine surveillance. Here we investigate the gains achievable by using increasingly sensitive methods with the aim to understand what diagnostic sensitivity is necessary to guide malaria interventions.; Venous blood samples were collected from participants in a cross-sectional survey in two coastal medium-endemic villages in Madang province, Papua New Guinea. Using ultra-sensitive quantitative PCR (us-qPCR) on concentrated high-volume blood samples (2 mL) as reference, we quantified the proportion of Plasmodium falciparum and Plasmodium vivax infections and gametocyte carriers detectable in fingerprick blood volumes (200 μL) by standard 18S rRNA qPCR, us-qPCR, rapid diagnostic test (RDT), and ultra-sensitive P falciparum RDT. We further compared the epidemiological patterns observed with each diagnostic approach in the study population.; Venous blood samples were collected from 300 participants between Dec 5, 2016, and Feb 24, 2017 (ie, during peak rainy season). Standard qPCR identified 87 (54%) of 161 P falciparum infections and 73 (52%) of 141 P vivax infections detected by the reference method. us-qPCR identified an additional 11 (7%) P falciparum infections and 14 (10%) P vivax infections. 80 (86%) of 93 P falciparum gametocyte carriers and 75 (91%) of 82 P vivax gametocyte carriers were found among infections detectable by us-qPCR. Ultra-sensitive RDT missed half of P falciparum infections detected by standard qPCR, including high gametocytaemic infections. Epidemiological patterns corresponded well between standard qPCR and the reference method. As the prevalence of P vivax decreased with increasing age, the proportion of P vivax infections undetectable by standard qPCR increased.; Almost all potentially transmitting parasite carriers were identified with us-qPCR on fingerprick blood volumes. Analysing larger blood volumes revealed a large pool of ultra-low-density P falciparum and P vivax infections, which are unlikely to be transmitted. Therefore, current RDTs cannot replace molecular diagnostics for identifying potential P falciparum transmitters.; Swiss National Science Foundation

Evaluation of Effect of Taxus baccata Leaves Extract on Bronchoconstriction and Bronchial Hyperreactivity in Experimental Animals

The present investigation was undertaken to evaluate the bronchodilating effect and bronchial hyperreactivity of alcoholic extract of Taxus baccata Linn. (AET) leaves in experimental animals. Bronchodilator activity of AET was studied on the histamine and acetylcholine aerosol induced bronchospasm in guinea pigs and bronchial hyperreactivity was studied on bronchoalveolar lavage fluid (BALF) in the egg albumin sensitized guinea pigs and by histopathological studies. In vitro mast cell stabilizing activity was studied using compound 48/80 as a degranulating agent. Treatment with AET (200 and 400 mg/kg, p.o., for 7 days) showed significant protection against histamine and acetylcholine aerosol induced bronchospasm in guinea pigs. Significant decrease in the total leukocyte and differential leukocyte count in the BALF of the egg albumin sensitized guinea pigs was observed by administration of AET (200 and 400 mg/kg, p.o., for 15 days). AET dose dependently protected the mast cell disruption induced by compound 48/80. These results suggest that AET not only has bronchodilating activity but also decreases bronchial hyperreactivity by decreasing the infiltration of inflammatory cells in the airway and inhibiting the release of histamine like mediators from the mast cell by stabilizing it

What Do Youth Service Librarians Need? Reassessing Goals and Curricula in the Context of Changing Information Needs and Behaviors of Youth

The ALISE Youth Services Special Interest Group (SIG) presents a panel that explores what “youth services” means in the context of LIS education today, including novel additions to youth services curricula and how the changing needs of youth impact LIS education. The session begins with five research presentations, followed by an open discussion and Q&A. The five presentations incorporate the following topics: critical youth information needs, methods of incorporating design thinking and interdisciplinary research into MLIS youth services courses, an investigation of dialogue between librarians and youth, and the role of family and community in youth information behavior. The discussion prompted by this scholarship serves as an important contribution to the continued reform and evolution of youth services education

Seasonal Distribution of Psychiatric Births in England

There is general consensus that season of birth influences the risk of developing psychiatric conditions later in life. We aimed to investigate whether the risk of schizophrenia (SC), bipolar affective disorder (BAD) and recurrent depressive disorder (RDD) is influenced by month of birth in England to a similar extent as other countries using the largest cohort of English patients collected to date (n=57,971). When cases were compared to the general English population (n=29,183,034) all diseases showed a seasonal distribution of births (SC p=2.48E-05; BAD p=0.019; RDD p=0.015). This data has implications for future strategies of disease prevention