Johanssonhurley6167

CONCLUSIONS We report a rare case of PLR caused by GEJ adenocarcinoma. This is the first case of PLR in a patient with metastatic GEJ adenocarcinoma with HER2 overexpression in the Caucasian population. It is important to workup leukocytosis promptly, to keep malignancy in the differential diagnosis and to seek early hematology/oncology consultation.A 74-year-old woman developed bilateral leg weakness, with fluctuating cognitive and systemic symptoms that progressed despite treatment. Her diagnosis was confirmed at autopsy. Her case was discussed at the Edinburgh Clinical Neurology Course 2019 Clinicopathological Conference. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.A 76-year-old man developed recurrent encephalopathy, visual disturbance, myoclonus, generalised seizures and atonic drop attacks on a background of a gastrectomy for adenocarcinoma and stable chronic lymphocytic leukaemia. He presented to three different hospitals and was admitted twice, with normal investigations. His symptoms transiently improved during each admission (and with starting levetiracetam) but recurred each time on hospital discharge. Subsequent careful inspection of his medication box identified that his community pharmacy had in error been dispensing baclofen 80 mg per day instead of his prescribed Buscopan 80 mg per day. This case highlights the importance of physically inspecting a patient's medications and emphasises the spectrum of baclofen-related toxicity; it also highlights potential deficiencies in the pharmacy dispensary process and the need for multiple checks by patients and professionals. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE We aimed to assess incidence and clearance of oral human papillomavirus (HPV) infection and the respective risk factors in HIV-infected and uninfected men who have sex with men (MSM). METHODS Oral rinse and gargles were collected semiannually from 244 MSM (103, 42.2% HIV-infected). HPV-DNA testing was performed with the Linear Array HPV Genotyping test. A Markov model was used for estimation of incidence, clearance and risk factor analysis. RESULTS Incidence rates for any HPV were 21.2 and 15.0×1000 person-months in HIV-infected and uninfected MSM, respectively. The respective figures for high-risk HPVs were 10.7 and 6.5×1000 person-months. The clearance rate was 4-12 times higher than the respective incidence rate. HIV-infected MSM with >95 lifetime oral sex partners showed increased incidence of any HPV (adjusted HR, aHR 8.46, 95% CI 1.89 to 37.92). Condomless oral sex appeared the strongest predictor for incident infection by high-risk HPVs in this group (aHR 13.40, 95% CI 2.55 to 70.53). Those aged >46 years (aHR 0.30, 95% CI 0.12 to 0.74) and those with nadir CD4+ T count of 46 years had increased risk of acquiring any HPV (aHR 3.70, 95% CI 1.30 to 10.52) and high-risk HPV (aHR 5.33, 95% CI 1.06 to 26.68). see more Any HPV clearance declined in those with more than six recent oral sex partners (aHR 0.18, 95% CI 0.05 to 0.65). CONCLUSIONS Acquisition of oral HPV infection in MSM seems to occur rarely, whereas clearance seems to be a frequent event. Oral HPV natural history in these at-risk subjects is differently influenced by age and sex behaviour, depending on HIV status. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE From December 2017, the Australian National Cervical Screening Program commenced 5 yearly primary human papillomavirus (HPV) screening; one of the first high-income countries to implement primary HPV screening. This study aimed to examine the psychosocial impact of self-reporting testing HPV positive in a sample of women screened since the renewal of the programme. METHODS Women in Australia aged 25-74 years who reported participating in cervical screening since December 2017 were recruited through an online market research company to complete a cross-sectional survey. The primary outcomes were anxiety and general distress. RESULTS 1004 women completed the online survey; 80.9% reported testing HPV negative (HPV-), 6.5% reported testing HPV positive (HPV+) and 12.9% did not know/remember their test result. Women who reported testing HPV+ had significantly poorer psychological outcomes on a range of measures. Those who reported testing HPV+ had higher anxiety scores (53.03 vs 43.58 out of 80, p less ts or by other interventions. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES We explored the association between nucleic acid amplification testing (NAAT) and rectal microscopy/proctoscopy findings and correlates of rectal STIs among 150 gay and bisexual men (GBM) diagnosed with proctitis at the Sydney Sexual Health Centre from March 2016 to October 2017. METHODS From case files, we analysed risk behaviours, microscopy, proctoscopy and NAAT results for rectal STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, herpes simplex virus type 1/2, lymphogranuloma venereum and syphilis). χ2 test assessed the association between microscopy/proctoscopy findings and NAAT results. Linear regression assessed the association between NAAT positivity and correlates of rectal STIs. RESULTS The mean age was 32.5 (9.8) years, 43% (65/150) were taking pre-exposure prophylaxis, 17% (26/150) were HIV positive and 24% (36/147) had multiple rectal STIs.Among GBM with documented proctoscopy findings (n=113), 58% (65/113) had discharge, 36% (41/113) had anorectal erythema and ctal STI. Services should consider recommendations to perform these investigations. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.The initiating mutations that contribute to cancer development are sometimes present in premalignant cells. Whether therapies targeting these mutations can eradicate premalignant cells is unclear. Acute myeloid leukemia (AML) is an attractive system for investigating the effect of preventative treatment because this disease is often preceded by a premalignant state (clonal hematopoiesis or myelodysplastic syndrome). In Npm1c/Dnmt3a mutant knock-in mice, a model of AML development, leukemia is preceded by a period of extended myeloid progenitor cell proliferation and self-renewal. We found that this self-renewal can be reversed by oral administration of a small molecule (VTP-50469) that targets the MLL1-Menin chromatin complex. These preclinical results support the hypothesis that individuals at high risk of developing AML might benefit from targeted epigenetic therapy in a preventative setting. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.Radio pulsars in short-period eccentric binary orbits can be used to study both gravitational dynamics and binary evolution. The binary system containing PSR J1141-6545 includes a massive white dwarf (WD) companion that formed before the gravitationally bound young radio pulsar. We observed a temporal evolution of the orbital inclination of this pulsar that we infer is caused by a combination of a Newtonian quadrupole moment and Lense-Thirring (LT) precession of the orbit resulting from rapid rotation of the WD. LT precession, an effect of relativistic frame dragging, is a prediction of general relativity. This detection is consistent with an evolutionary scenario in which the WD accreted matter from the pulsar progenitor, spinning up the WD to a period of less then 200 seconds. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.Honey bees are essential pollinators threatened by colony losses linked to the spread of parasites and pathogens. Here, we report a new approach for manipulating bee gene expression and protecting bee health. We engineered a symbiotic bee gut bacterium, Snodgrassella alvi, to induce eukaryotic RNA interference (RNAi) immune responses. We show that engineered S. alvi can stably recolonize bees and produce double-stranded RNA to activate RNAi and repress host gene expression, thereby altering bee physiology, behavior, and growth. We used this approach to improve bee survival after a viral challenge, and we show that engineered S. alvi can kill parasitic Varroa mites by triggering the mite RNAi response. This symbiont-mediated RNAi approach is a tool for studying bee functional genomics and potentially for safeguarding bee health. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.Africa, the ancestral home of all modern humans, is the most informative continent for understanding the human genome and its contribution to complex disease. To better understand the genetics of schizophrenia, we studied the illness in the Xhosa population of South Africa, recruiting 909 cases and 917 age-, gender-, and residence-matched controls. Individuals with schizophrenia were significantly more likely than controls to harbor private, severely damaging mutations in genes that are critical to synaptic function, including neural circuitry mediated by the neurotransmitters glutamine, γ-aminobutyric acid, and dopamine. Schizophrenia is genetically highly heterogeneous, involving severe ultrarare mutations in genes that are critical to synaptic plasticity. The depth of genetic variation in Africa revealed this relationship with a moderate sample size and informed our understanding of the genetics of schizophrenia worldwide. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.Electron backscatter diffraction (EBSD) is one of the primary tools for crystal structure determination. However, this method requires human input to select potential phases for Hough-based or dictionary pattern matching and is not well suited for phase identification. Automated phase identification is the first step in making EBSD into a high-throughput technique. We used a machine learning-based approach and developed a general methodology for rapid and autonomous identification of the crystal symmetry from EBSD patterns. We evaluated our algorithm with diffraction patterns from materials outside the training set. The neural network assigned importance to the same symmetry features that a crystallographer would use for structure identification. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.Stereochemical control in the construction of carbon-carbon bonds between an alkyl electrophile and an alkyl nucleophile is a persistent challenge in organic synthesis. Classical substitution reactions via SN1 and SN2 pathways are limited in their ability to generate carbon-carbon bonds (inadequate scope, due to side reactions such as rearrangements and eliminations) and to control stereochemistry when beginning with readily available racemic starting materials (racemic products). Here, we report a chiral nickel catalyst that couples racemic electrophiles (propargylic halides) with racemic nucleophiles (β-zincated amides) to form carbon-carbon bonds in doubly stereoconvergent processes, affording a single stereoisomer of the product from two stereochemical mixtures of reactants. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.