Oral Cancer Prevalence in Virginia

Purpose. Oral and pharyngeal cancer affects 30,000 Americans a year and kills one fourth of those diagnosed. The primary risk factors for oral cancer are past or present cigarette and tobacco usage, and alcohol consumption in conjunction with tobacco use. Even though the prevalence of oral cancer is relatively low in the younger age groups, this group is most likely to benefit from intervention programs designed to change risky behavior such as smoking, and to prevent oral cancer in the later years. The goal of the study was to identify high-risk target areas for an oral cancer prevention program in Virginia. Methods and Materials. The specific objectives were to analyze the 1986 to 2001 Oral Biopsy Database from the Virginia Commonwealth University School of Dentistry for diagnosed cases of oral cancer. To test the hypothesis that Hampton Roads, Virginia would be a high-risk target area, diagnoses were correlated with the 11 zip-code regions in Virginia to identify specific geographical areas with high numbers of oral cancer cases. The oral cancer data set consisted of 4,712 cases. Frequencies and cross-tabulations were calculated for all the variables using Statistical Package for Social Scientists software (SPSS Inc., version 10.1, Chicago, IL). Results. Results indicated that the Hampton Roads region had the second highest number of squamous cell carcinomas, with 231 total cases. The Richmond area had 435cases, almost twice as many. Conclusions. Therefore, Hampton Roads and Richmond are high-risk target areas that would benefit from an aggressive oral cancer prevention and intervention program in its public schools

DNA fragility in the parallel evolution of pelvic reduction in stickleback fish

Evolution generates a remarkable breadth of living forms, but many traits evolve repeatedly, by mechanisms that are still poorly understood. A classic example of repeated evolution is the loss of pelvic hindfins in stickleback fish (Gasterosteus aculeatus). Repeated pelvic loss maps to recurrent deletions of a pelvic enhancer of the Pitx1 gene. Here, we identify molecular features contributing to these recurrent deletions. Pitx1 enhancer sequences form alternative DNA structures in vitro and increase double-strand breaks and deletions in vivo. Enhancer mutability depends on DNA replication direction and is caused by TG-dinucleotide repeats. Modeling shows that elevated mutation rates can influence evolution under demographic conditions relevant for sticklebacks and humans. DNA fragility may thus help explain why the same loci are often used repeatedly during parallel adaptive evolution

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

Neurobehaviour between birth and 40 weeks’ gestation in infants born <30 weeks’ gestation and parental psychological wellbeing: predictors of brain development and child outcomes

BACKGROUND: Infants born <30 weeks’ gestation are at increased risk of long term neurodevelopmental problems compared with term born peers. The predictive value of neurobehavioural examinations at term equivalent age in very preterm infants has been reported for subsequent impairment. Yet there is little knowledge surrounding earlier neurobehavioural development in preterm infants prior to term equivalent age, and how it relates to perinatal factors, cerebral structure, and later developmental outcomes. In addition, maternal psychological wellbeing has been associated with child development. Given the high rate of psychological distress reported by parents of preterm children, it is vital we understand maternal and paternal wellbeing in the early weeks and months after preterm birth and how this influences the parent–child relationship and children’s outcomes. Therefore this study aims to examine how 1) early neurobehaviour and 2) parental mental health relate to developmental outcomes for infants born preterm compared with infants born at term. METHODS/DESIGN: This prospective cohort study will describe the neurobehaviour of 150 infants born at <30 weeks’ gestational age from birth to term equivalent age, and explore how early neurobehavioural deficits relate to brain growth or injury determined by magnetic resonance imaging, perinatal factors, parental mental health and later developmental outcomes measured using standardised assessment tools at term, one and two years’ corrected age. A control group of 150 healthy term-born infants will also be recruited for comparison of outcomes. To examine the effects of parental mental health on developmental outcomes, both parents of preterm and term-born infants will complete standardised questionnaires related to symptoms of anxiety, depression and post-traumatic stress at regular intervals from the first week of their child’s birth until their child’s second birthday. The parent–child relationship will be assessed at one and two years’ corrected age. DISCUSSION: Detailing the trajectory of infant neurobehaviour and parental psychological distress following very preterm birth is important not only to identify infants most at risk, further understand the parental experience and highlight potential times for intervention for the infant and/or parent, but also to gain insight into the effect this has on parent–child interaction and child development

The evolution of drug resistance in clinical isolates of Candida albicans

Candida albicans is both a member of the healthy human microbiome and a major pathogen in immunocompromised individuals. Infections are typically treated with azole inhibitors of ergosterol biosynthesis often leading to drug resistance. Studies in clinical isolates have implicated multiple mechanisms in resistance, but have focused on large-scale aberrations or candidate genes, and do not comprehensively chart the genetic basis of adaptation. Here, we leveraged next-generation sequencing to analyze 43 isolates from 11 oral candidiasis patients. We detected newly selected mutations, including single-nucleotide polymorphisms (SNPs), copy-number variations and loss-of-heterozygosity (LOH) events. LOH events were commonly associated with acquired resistance, and SNPs in 240 genes may be related to host adaptation. Conversely, most aneuploidies were transient and did not correlate with drug resistance. Our analysis also shows that isolates also varied in adherence, filamentation, and virulence. Our work reveals new molecular mechanisms underlying the evolution of drug resistance and host adaptation.National Science Foundation (U.S.). Graduate Research Fellowship ProgramHoward Hughes Medical InstituteHelen Hay Whitney Foundation (Postdoctoral Fellowship)Alfred P. Sloan FoundationNational Institutes of Health (U.S.) (Grant 8DP1CA174427)National Institutes of Health (U.S.) (Grant 2R01CA119176-01

Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes.

The natriuretic peptides, Atrial-, B-type and C-type natriuretric peptides (ANP, BNP, CNP), are regulators of many endocrine tissues and exert their effects predominantly through the activation of their specific guanylyl cyclase receptors (GC-A and GC-B) to generate cGMP. Whereas cGMP-independent signalling has been reported in response to natriuretic peptides, this is mediated via either the clearance receptor (Npr-C) or a renal-specific NPR-Bi isoform, which both lack intrinsic guanylyl cyclase activity. Here, we report evidence of GC-B-dependent cGMP-independent signalling in pituitary GH3 cells. Stimulation of GH3 cells with CNP resulted in a rapid and sustained enhancement of ERK1/2 phosphorylation (P-ERK1/2), an effect that was not mimicked by dibutryl-cGMP. Furthermore, CNP-stimulated P-ERK1/2 occurred at concentrations below that required for cGMP accumulation. The effect of CNP on P-ERK1/2 was sensitive to pharmacological blockade of MEK (U0126) and Src kinases (PP2). Silencing of the GC-B1 and GC-B2 splice variants of the GC-B receptor by using targeted short interfering RNAs completely blocked the CNP effects on P-ERK1/2. CNP failed to alter GH3 cell proliferation or cell cycle distribution but caused a concentration-dependent increase in the activity of the human glycoprotein α-subunit promoter (αGSU) in a MEK-dependent manner. Finally, CNP also activated the p38 and JNK MAPK pathways in GH3 cells. These findings reveal an additional mechanism of GC-B signalling and suggest additional biological roles for CNP in its target tissues

Improving the outcome of infants born at <30 weeks' gestation - a randomized controlled trial of preventative care at home

Background: Early developmental interventions to prevent the high rate of neurodevelopmental problems in very preterm children, including cognitive, motor and behavioral impairments, are urgently needed. These interventions should be multi-faceted and include modules for caregivers given their high rates of mental health problems

Roadmap for a sustainable circular economy in lithium-ion and future battery technologies

The market dynamics, and their impact on a future circular economy for lithium-ion batteries (LIB), are presented in this roadmap, with safety as an integral consideration throughout the life cycle. At the point of end-of-life (EOL), there is a range of potential options—remanufacturing, reuse and recycling. Diagnostics play a significant role in evaluating the state-of-health and condition of batteries, and improvements to diagnostic techniques are evaluated. At present, manual disassembly dominates EOL disposal, however, given the volumes of future batteries that are to be anticipated, automated approaches to the dismantling of EOL battery packs will be key. The first stage in recycling after the removal of the cells is the initial cell-breaking or opening step. Approaches to this are reviewed, contrasting shredding and cell disassembly as two alternative approaches. Design for recycling is one approach that could assist in easier disassembly of cells, and new approaches to cell design that could enable the circular economy of LIBs are reviewed. After disassembly, subsequent separation of the black mass is performed before further concentration of components. There are a plethora of alternative approaches for recovering materials; this roadmap sets out the future directions for a range of approaches including pyrometallurgy, hydrometallurgy, short-loop, direct, and the biological recovery of LIB materials. Furthermore, anode, lithium, electrolyte, binder and plastics recovery are considered in order to maximise the proportion of materials recovered, minimise waste and point the way towards zero-waste recycling. The life-cycle implications of a circular economy are discussed considering the overall system of LIB recycling, and also directly investigating the different recycling methods. The legal and regulatory perspectives are also considered. Finally, with a view to the future, approaches for next-generation battery chemistries and recycling are evaluated, identifying gaps for research. This review takes the form of a series of short reviews, with each section written independently by a diverse international authorship of experts on the topic. Collectively, these reviews form a comprehensive picture of the current state of the art in LIB recycling, and how these technologies are expected to develop in the future

Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1^st(7.4 μg/m³) to the 25^th(17.2 μg/m³), 50^th(33.8 μg/m³), 75^th(108.3 μg/m³), and 90^th(180.8 μg/m³) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

Elite squash players nutrition knowledge and influencing factors

Background There is a reported mismatch between macronutrient consumption and contemporary macronutrient guidelines in elite standard squash players. Suboptimal dietary practices could be due to a lack of nutrition knowledge among players. Subsequently, the purpose of this study was to assess the sports nutrition knowledge of elite squash players through the Nutrition for Sport Knowledge Questionnaire (NSKQ) and provide an indication of whether players require nutrition support to increase their nutrition knowledge. Methods This cross-sectional study assessed the nutrition knowledge of 77 elite squash players via the NSKQ over the period of June 2020 to August 2020. Results Players conveyed average nutrition knowledge with a mean NSKQ score of 48.78 ± 10.06 (56.07% ± 11.56%). There were no significant differences in NSKQ score between male and female players (p = .532). There was found to be a weak positive association between world ranking and NSKQ score (r = .208) and age and NSKQ score (r = .281). Players who had a relevant undergraduate degree (e.g. BSc Sport & Exercise Science) had significantly greater NSKQ score than players with no relevant qualifications (p = .022). Players who consulted a sports nutritionist to obtain their main source of nutrition information were shown to have significantly greater knowledge than those who acquired knowledge from a sports scientist (p = .01) or the internet / social media (p = .007). Conclusions Players should consult with a sports nutritionist to increase their sport nutrition knowledge. Future research should quantify the effectiveness of a nutritional education intervention at increasing nutrition knowledge in players