Since industrialization began, atmospheric CO2 (CO2) has increased from 270 to 415 ppm and is projected to reach 800-1000 ppm this century. Some Arabidopsis thaliana (Arabidopsis) genotypes delayed ...flowering in elevated CO2 relative to current CO2, while others showed no change or accelerations. To predict genotype-specific flowering behaviors, we must understand the mechanisms driving flowering response to rising CO2. CO2 changes alter photosynthesis and carbohydrates in plants. Plants sense carbohydrate levels, and exogenous carbohydrate application influences flowering time and flowering transcript levels. We asked how organismal changes in carbohydrates and transcription correlate with changes in flowering time under elevated CO2. We used a genotype (SG) of Arabidopsis that was selected for high fitness at elevated CO2 (700 ppm). SG delays flowering under elevated CO2 (700 ppm) relative to current CO2 (400 ppm). We compared SG to a closely related control genotype (CG) that shows no CO2-induced flowering change. We compared metabolomic and transcriptomic profiles in these genotypes at current and elevated CO2 to assess correlations with flowering in these conditions. While both genotypes altered carbohydrates in response to elevated CO2, SG had higher levels of sucrose than CG and showed a stronger increase in glucose and fructose in elevated CO2. Both genotypes demonstrated transcriptional changes, with CG increasing genes related to fructose 1,6-bisphosphate breakdown, amino acid synthesis, and secondary metabolites; and SG decreasing genes related to starch and sugar metabolism, but increasing genes involved in oligosaccharide production and sugar modifications. Genes associated with flowering regulation within the photoperiod, vernalization, and meristem identity pathways were altered in these genotypes. Elevated CO2 may alter carbohydrates to influence transcription in both genotypes and delayed flowering in SG. Changes in the oligosaccharide pool may contribute to delayed flowering in SG. This work extends the literature exploring genotypic-specific flowering responses to elevated CO2.
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Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity for breast cancer patients that leads to early treatment discontinuation and worse ...outcomes. Neuromuscular ultrasound (NMUS) is a non-invasive assessment of peripheral nerves that has not been studied in taxane CIPN. Methods: This cross-sectional study enrolled breast cancer patients with subjective complaints of CIPN symptoms during or after taxane chemotherapy and compared nerve cross-sectional area (CSA) by NMUS with historical values in 120 healthy adults. Findings were correlated with self-reported symptom scale (EORTC-QLQ CIPN20, range 0-72, higher more severe); nerve conduction studies; and skin biopsies for intraepidermal nerve fiber density (IENF). Results: We evaluated 20 participants (mean 55.4 ± 10.5 yrs) with NMUS at 74 nerve sites after median 3.7 months (IQR 1.0-6.1) since last taxane (paclitaxel 10, docetaxel 8, nab-paclitaxel 2). Participants reported moderate-to-severe CIPN symptoms which were predominantly sensory (19.1 ±4.9, max 32) as opposed to motor (15.6 ±5.8, max 32) or autonomic (3.3 ±1.6, max 8). Sural sensory nerve CSA was 1.2 mm
2
smaller than in historical controls (4.1 vs. 5.3 mm
2
, 2-sample t-test p = 0.005) and decreased with more days from last taxane (Spearman’s r -0.46, p = 0.04). Tibial motor nerve was not significantly different from controls (p = 0.35). Median nerve CSA was enlarged at the distal wrist crease entrapment site (12.5 vs 10.1, p = 0.03). Older age was associated with smaller sural CSA (r = -0.72, p < 0.001). When controlling for age and days from last taxane, for each 1mm
2
decrease in sural CSA, distal IENF reduced by 2.1 nerve/mm
2
(p = 0.04, R
2
= 0.30). Conclusions: NMUS showed expected sensory predominant distal axonopathy in taxane CIPN. Evaluation of nerve CSA by non-invasive NMUS may serve as an objective point-of-care assessment to risk-stratify women with taxane CIPN prior to the development of debilitating symptoms. Clinical trial information: NCT03139435. Table: see text
Of the 132 people known to have been infected with H7N9 influenza viruses in China, 37 died, and many were severely ill. Infection seems to have involved contact with infected poultry. We have ...examined the receptor-binding properties of this H7N9 virus and compared them with those of an avian H7N3 virus. We find that the human H7 virus has significantly higher affinity for α-2,6-linked sialic acid analogues ('human receptor') than avian H7 while retaining the strong binding to α-2,3-linked sialic acid analogues ('avian receptor') characteristic of avian viruses. The human H7 virus does not, therefore, have the preference for human versus avian receptors characteristic of pandemic viruses. X-ray crystallography of the receptor-binding protein, haemagglutinin (HA), in complex with receptor analogues indicates that both human and avian receptors adopt different conformations when bound to human H7 HA than they do when bound to avian H7 HA. Human receptor bound to human H7 HA exits the binding site in a different direction to that seen in complexes formed by HAs from pandemic viruses and from an aerosol-transmissible H5 mutant. The human-receptor-binding properties of human H7 probably arise from the introduction of two bulky hydrophobic residues by the substitutions Gln226Leu and Gly186Val. The former is shared with the 1957 H2 and 1968 H3 pandemic viruses and with the aerosol-transmissible H5 mutant. We conclude that the human H7 virus has acquired some of the receptor-binding characteristics that are typical of pandemic viruses, but its retained preference for avian receptor may restrict its further evolution towards a virus that could transmit efficiently between humans, perhaps by binding to avian-receptor-rich mucins in the human respiratory tract rather than to cellular receptors.
Oriol Mitjà * E-mail: oriol.mitja@isglobal.org Affiliations Skin NTDs Program, Barcelona Institute for Global Health, Hospital Clinic-University of Barcelona, Barcelona, Spain, Division of Public ...Health, School of Medicine and Health Sciences, University of Papua New Guinea, Port Moresby, Papua New Guinea ORCID http://orcid.org/0000-0003-3266-8868 Michael Marks Affiliations Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom, Hospital for Tropical Diseases, University College London Hospitals NHS Trust, London, United Kingdom ORCID http://orcid.org/0000-0002-7585-4743 Laia Bertran Affiliation: Skin NTDs Program, Barcelona Institute for Global Health, Hospital Clinic-University of Barcelona, Barcelona, Spain Karsor Kollie Affiliation: Neglected Tropical and Non Communicable Diseases Program, Ministry of Health, Government of Liberia, Liberia Daniel Argaw Affiliation: Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland Ahmed H. Fahal Affiliation: The Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan Christopher Fitzpatrick Affiliation: Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland L. Claire Fuller Affiliation: International Foundation for Dermatology, London, United Kingdom Bernardo Garcia Izquierdo Affiliation: Anesvad foundation, Bilbao, Spain Roderick Hay Affiliation: International Foundation for Dermatology, London, United Kingdom Norihisa Ishii Affiliation: Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan Christian Johnson Affiliation: Fondation Raoul Follereau, Cotonou, République du Bénin Jeffrey V. Lazarus Affiliation: Skin NTDs Program, Barcelona Institute for Global Health, Hospital Clinic-University of Barcelona, Barcelona, Spain Anthony Meka Affiliation: Medical Department, German Leprosy and TB Relief Association, Enugu, Nigeria Michele Murdoch Affiliation: Department of Dermatology, Watford General Hospital, Watford, United Kingdom Sally-Ann Ohene Affiliation: World Health Organization Country Office, Accra, Ghana Pam Small Affiliation: Department of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America Andrew Steer Affiliation: Group A Streptococcal Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia Earnest N. Tabah Affiliation: National Yaws, Leishmaniasis, Leprosy and Buruli ulcer Control Programme, Ministry of Public Health, Yaoundé, Cameroon Alexandre Tiendrebeogo Affiliation: World Health Organization Regional Office for Africa, Brazzaville, Congo Lance Waller Affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America Rie Yotsu Affiliation: Department of Dermatology, National Center for Global Health and Medicine, Tokyo, Japan Stephen L. Walker Affiliation: Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom Kingsley Asiedu Affiliation: Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, SwitzerlandCitation: Mitjà O, Marks M, Bertran L, Kollie K, Argaw D, Fahal AH, et al. Research * Validating a clinical algorithm for identification of skin NTDs using key symptoms and signs. * Developing common clinical and laboratory diagnostic platforms for these diseases, which are practical in the field. * Mapping to identify their overlap to allow integrated coordinated control and treatment activities as well as health system strengthening for service delivery. * Piloting the integrated approach in one or several regions. * Better understanding of the epidemiology of these diseases including transmission and interaction with poverty and water, sanitation, and hygiene (WASH). * Understand community resilience and program factors that strengthen community participation.
The dose-dense delivery of chemotherapy (greater frequency of drug delivery) was explored in women with advanced ovarian cancer. All patients received carboplatin; half received paclitaxel weekly and ...half every 3 weeks. There were no between-group differences in progression-free survival.
Ovarian cancer, the most lethal gynecologic cancer, is responsible for approximately 14,000 deaths in the United States annually.
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The incorporation of bevacizumab, a monoclonal antibody against vascular endothelial growth factor, in the treatment regimen prolongs progression-free survival but not overall survival.
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–
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A dose-dense regimen of paclitaxel involving greater frequency of drug delivery may enhance its antineoplastic effect by eliciting antiangiogenic and proapoptotic properties.
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–
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Weekly paclitaxel therapy prolonged survival among patients with early-stage breast cancer and those with metastatic breast cancer.
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,
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In a study involving patients with ovarian cancer, Japanese investigators found that dose-dense weekly paclitaxel prolonged progression-free . . .
Scabies outbreaks in residential and nursing care homes for elderly people are common, subject to diagnostic delay, and hard to control. We studied clinical features, epidemiology, and outcomes of ...outbreaks in the UK between 2014 and 2015.
We did a prospective observational study in residential care homes for elderly people in southeast England that reported scabies outbreaks to Public Health England health protection teams. An outbreak was defined as two or more cases of scabies (in either residents or staff) at a single care home. All patients who provided informed consent were included; patients with dementia were included if a personal or nominated consultee (ie, a family member or nominated staff member) endorsed participation. Dermatology-trained physicians examined residents at initial clinical visits, which were followed by two mass treatments with topical scabicide as per local health protection team guidance. Follow-up clinical visits were held 6 weeks after initial visits. Scabies was diagnosed through pre-defined case definitions as definite, probable, or possible with dermatoscopy and microscopy as appropriate.
230 residents were examined in ten outbreaks between Jan 23, 2014, and April 13, 2015. Median age was 86·9 years (IQR 81·5–92·3), 174 (76%) were female, and 157 (68%) had dementia. 61 (27%) residents were diagnosed with definite, probable, or possible scabies, of whom three had crusted scabies. Physical signs differed substantially from classic presentations. 31 (51%) of the 61 people diagnosed with scabies were asymptomatic, and only 25 (41%) had burrows. Mites were visualised with dermatoscopy in seven (11%) patients, and further confirmed by microscopy in three (5%). 35 (57%) cases had signs of scabies only on areas of the body that would normally be covered. Dementia was the only risk factor for a scabies diagnosis that we identified (odds ratio 2·37 95% CI 1·38–4·07). At clinical follow-up, 50 people who were initially diagnosed with scabies were examined. No new cases of scabies were detected, but infestation persisted in ten people.
Clinical presentation of scabies in elderly residents of care homes differs from classic descriptions familiar to clinicians. This difference probably contributes to delayed recognition and suboptimal management in this vulnerable group. Dermatoscopy and microscopy were of little value. Health-care workers should be aware of the different presentation of scabies in elderly people, and should do thorough examinations, particularly in people with dementia.
Public Health England and British Skin Foundation.
Syntrophic interspecies electron exchange is essential for the stable functioning of diverse anaerobic microbial communities. Hydrogen/formate interspecies electron transfer (HFIT), in which H
and/or ...formate function as diffusible electron carriers, has been considered to be the primary mechanism for electron transfer because most common syntrophs were thought to lack biochemical components, such as electrically conductive pili (e-pili), necessary for direct interspecies electron transfer (DIET). Here we report that Syntrophus aciditrophicus, one of the most intensively studied microbial models for HFIT, produces e-pili and can grow via DIET. Heterologous expression of the putative S. aciditrophicus type IV pilin gene in Geobacter sulfurreducens yielded conductive pili of the same diameter (4 nm) and conductance of the native S. aciditrophicus pili and enabled long-range electron transport in G. sulfurreducens. S. aciditrophicus lacked abundant c-type cytochromes often associated with DIET. Pilin genes likely to yield e-pili were found in other genera of hydrogen/formate-producing syntrophs. The finding that DIET is a likely option for diverse syntrophs that are abundant in many anaerobic environments necessitates a reexamination of the paradigm that HFIT is the predominant mechanism for syntrophic electron exchange within anaerobic microbial communities of biogeochemical and practical significance.
This study evaluated the effectiveness of a school-based mental health literacy intervention for adolescents on knowledge and stigma.
A total of 24 high schools and 534 students in the regional area ...of Ottawa, Ontario, Canada participated in this randomized controlled trial. Schools were randomly assigned to either the curriculum or control condition. The curriculum was integrated into the province's grade 11 and 12 "Healthy Living" courses and was delivered by teachers. Changes in mental health knowledge and stigma were measured using pre- and posttest questionnaires. Descriptive analyses were conducted to provide sample characteristics, and multilevel modeling was used to examine study outcomes.
For the curriculum condition, there was a significant change in stigma scores over time (p = .001), with positive attitudes toward mental illness increasing from pre to post. There was also a significant change in knowledge scores over time (p < .001), with knowledge scores increasing from pre to post. No significant changes in knowledge or stigma were found for participants in the control condition. A meaningful relationship was found whereby increases in knowledge significantly predicted increases in positive attitudes toward mental health (p < .001).
This is the first large randomized controlled trial to demonstrate the effectiveness in mental health literacy of an integrated, manualized mental health educational resource for high school students on knowledge and stigma. Findings also support the applicability by teachers and suggest the potential for broad-based implementation of the educational curriculum in high schools. Replication and further studies are warranted. Clinical trial registration information-Impact of a Mental Health Curriculum for High School Students on Knowledge and Stigma; http://clinicaltrials.gov/; NCT02561780.
The RecQ DNA helicase WRN is a synthetic lethal target for cancer cells with microsatellite instability (MSI), a form of genetic hypermutability that arises from impaired mismatch repair
. Depletion ...of WRN induces widespread DNA double-strand breaks in MSI cells, leading to cell cycle arrest and/or apoptosis. However, the mechanism by which WRN protects MSI-associated cancers from double-strand breaks remains unclear. Here we show that TA-dinucleotide repeats are highly unstable in MSI cells and undergo large-scale expansions, distinct from previously described insertion or deletion mutations of a few nucleotides
. Expanded TA repeats form non-B DNA secondary structures that stall replication forks, activate the ATR checkpoint kinase, and require unwinding by the WRN helicase. In the absence of WRN, the expanded TA-dinucleotide repeats are susceptible to cleavage by the MUS81 nuclease, leading to massive chromosome shattering. These findings identify a distinct biomarker that underlies the synthetic lethal dependence on WRN, and support the development of therapeutic agents that target WRN for MSI-associated cancers.
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