Analysis of the Inverse Association between Cancer and Alzheimer’s Disease: Results from the Alzheimer’s Disease Neuroimaging Initiative Cohort

poster abstractAlthough a number of studies support a reciprocal inverse association between diagnoses of cancer and Alzheimer’s disease (AD), to date there has not been any systemic investigation of the neurobiological impact of or genetic risk factors underlying this effect. To facilitate this goal, this study aimed to replicate the inverse association of cancer and AD using data from the NIA Alzheimer’s Disease Neuroimaging Initiative, which includes age-matched cases and controls with information on cancer history, AD progression, neuroimaging, and genomic data. Subjects included individuals with AD (n=234), mild cognitive impairment (MCI, n=542), and healthy controls (HC, n=293). After controlling for sex, education, race/ethnicity, smoking, and apolipoprotein E (APOE) e2/3/4 allele groups, cancer history was protective against baseline AD diagnosis (p=0.042), and was associated with later age of AD onset (p=0.001). Cancer history appears to result in a cumulative protective effect; individuals with more than one cancer had a later age of AD onset compared to those with only one cancer (p=0.001). Finally, a protective effect of AD was also observed in individuals who developed incident cancer after enrolling (post-baseline visit); 20 individuals with MCI and 9 HC developed cancer, while no AD patients had subsequent cancer diagnoses (p=0.013). This supports previous research on the inverse association of cancer and AD, and importantly provides novel evidence that this effect appears to be independent of APOE, the major known genetic risk factor for AD. Future analyses will investigate the neurobiological and genetic basis of this effect

Lixo registrado em áreas livres de gelo em uma Área Antártica Especialmente Gerenciada (AAEG): Baía do Almirantado, ilha Rei George, Península Antártica

The Protocol on Environmental Protection to the Antarctic Treaty, or Madri Protocol - 1991, was created with the objective of preventing the contamination of the Antarctic environment and to guarantee the preservation of its natural resources. From the past to the presented time the Antarctic is considered a special area for conservation because it has exclusive environmental characteristics. Admiralty Bay, located on King George Island (South Shetland), is an Antarctic Specially Managed Area (ASMA) and, at the moment, there are five international stations located there. Since the beginning of its human occupation in 1819, with the arrival of the first sailors a lot of environmental changes can be register. This paper makes the first register of debris in this area, based on studies carried out during the summers of 2002/2003, 2003/2004 and 2004/2005. In total, 186 items were recorded as debris. In our study the majority of the debris was composed of wood (49%), followed by synthetic materials: metal (18%), plastic (16%), miscellaneous (16%) and cement (1%). However, what we can observe is that most of the recorded debris for Admiralty Bay comes from research activities (38%), resulting from remaining construction debris of research support; or equally, abandoned experiments, whose structures were not removed. Key words: South Shetland Island, Admiralty Bay, waste, pollution, environmental impact.O Protocolo sobre Proteção Ambiental do Tratado Antártico, ou Protocolo de Madri, foi criado com o objetivo de prevenir a contaminação do meio ambiente antártico e garantir a preservação dos seus recursos naturais. Desde o passado e ainda no presente, a Antártica é considerada uma área especial para a conservação devido às suas características ambientais únicas. A Baía do Almirantado, localizada na ilha Rei George (Shetland do Sul), é uma Área Antártica Especialmente Gerenciada (AAEG) e, até o presente, tem cinco estações científicas internacionais localizadas na região. Desde o início da ocupação humana em 1819, com a chegada dos primeiros caçadores de baleias, muitas alterações ambientais vêm sendo registradas. Este artigo faz o primeiro registro do lixo encontrado nesta área, baseado em estudos desenvolvidos durante os verões de 2002/2003, 2003/2004 e 2004/2005. No total, 186 itens foram registrados como lixo encontrado na área. A maioria do lixo encontrado foi composta por madeira (49%), seguida por materiais sintéticos: metal (18%), plástico (16%), material variado (16%) e cimento (1%). Foi constatado que a maior parte do lixo registrado em nosso estudo na Baía do Almirantado resulta de atividades científicas, sendo composto de restos de construções para suporte à pesquisa e também oriundos de experimentos científicos abandonados, nos quais a estrutura não foi removida após o fim do experimento. Palavras-chave: ilhas Shetland do Sul, Baía do Almirantado, lixo, poluição, impacto ambiental

Prenatal origin of childhood AML occurs less frequently than in childhood ALL

Background While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers. Methods We analysed Guthrie cards of 12 ALL patients aged 2–6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1–14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1–3 positive cells were present in the neonatal blood spot. Results In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML. Conclusion In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases

Diaphragmatic rupture with right colon and small intestine herniation after blunt trauma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Traumatic diaphragmatic hernias are an unusual presentation of trauma, and are observed in about 10% of diaphragmatic injuries. The diagnosis is often missed because of non-specific clinical signs, and the absence of additional intra-abdominal and thoracic injuries.</p> <p>Case presentation</p> <p>We report a case of a 59-year-old Italian man hospitalized for abdominal pain and vomiting. His medical history included a blunt trauma seven years previously. A chest X-ray showed right diaphragm elevation, and computed tomography revealed that the greater omentum, a portion of the colon and the small intestine had been transposed in the hemithorax through a diaphragm rupture. The patient underwent laparotomy, at which time the colon and small intestine were reduced back into the abdomen and the diaphragm was repaired.</p> <p>Conclusions</p> <p>This was a unusual case of traumatic right-sided diaphragmatic hernia. Diaphragmatic ruptures may be revealed many years after the initial trauma. The suspicion of diaphragmatic rupture in a patient with multiple traumas contributes to early diagnosis. Surgical repair remains the only curative treatment for diaphragmatic hernias. Prosthetic patches may be a good solution when the diaphragmatic defect is severe and too large for primary closure, whereas primary repair remains the gold standard for the closure of small to moderate sized diaphragmatic defects.</p

Status of Muon Collider Research and Development and Future Plans

The status of the research on muon colliders is discussed and plans are outlined for future theoretical and experimental studies. Besides continued work on the parameters of a 3-4 and 0.5 TeV center-of-mass (CoM) energy collider, many studies are now concentrating on a machine near 0.1 TeV (CoM) that could be a factory for the s-channel production of Higgs particles. We discuss the research on the various components in such muon colliders, starting from the proton accelerator needed to generate pions from a heavy-Z target and proceeding through the phase rotation and decay ($\pi \to \mu \nu_{\mu}$) channel, muon cooling, acceleration, storage in a collider ring and the collider detector. We also present theoretical and experimental R & D plans for the next several years that should lead to a better understanding of the design and feasibility issues for all of the components. This report is an update of the progress on the R & D since the Feasibility Study of Muon Colliders presented at the Snowmass'96 Workshop [R. B. Palmer, A. Sessler and A. Tollestrup, Proceedings of the 1996 DPF/DPB Summer Study on High-Energy Physics (Stanford Linear Accelerator Center, Menlo Park, CA, 1997)].Comment: 95 pages, 75 figures. Submitted to Physical Review Special Topics, Accelerators and Beam

Structural Biology of Human H3K9 Methyltransferases

SET domain methyltransferases deposit methyl marks on specific histone tail lysine residues and play a major role in epigenetic regulation of gene transcription. We solved the structures of the catalytic domains of GLP, G9a, Suv39H2 and PRDM2, four of the eight known human H3K9 methyltransferases in their apo conformation or in complex with the methyl donating cofactor, and peptide substrates. We analyzed the structural determinants for methylation state specificity, and designed a G9a mutant able to tri-methylate H3K9. We show that the I-SET domain acts as a rigid docking platform, while induced-fit of the Post-SET domain is necessary to achieve a catalytically competent conformation. We also propose a model where long-range electrostatics bring enzyme and histone substrate together, while the presence of an arginine upstream of the target lysine is critical for binding and specificity. Enhanced version: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available i

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Probiotic Bacteria Induce a ‘Glow of Health’

Radiant skin and hair are universally recognized as indications of good health. However, this ‘glow of health’ display remains poorly understood. We found that feeding of probiotic bacteria to aged mice induced integumentary changes mimicking peak health and reproductive fitness characteristic of much younger animals. Eating probiotic yogurt triggered epithelial follicular anagen-phase shift with sebocytogenesis resulting in thick lustrous fur due to a bacteria-triggered interleukin-10-dependent mechanism. Aged male animals eating probiotics exhibited increased subcuticular folliculogenesis, when compared with matched controls, yielding luxuriant fur only in probiotic-fed subjects. Female animals displayed probiotic-induced hyperacidity coinciding with shinier hair, a feature that also aligns with fertility in human females. Together these data provide insights into mammalian evolution and novel strategies for integumentary health

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07