The gray matter structural connectome and its relationship to alcohol relapse: Reconnecting for recovery.

Gray matter (GM) atrophy associated with alcohol use disorders (AUD) affects predominantly the frontal lobes. Less is known how frontal lobe GM loss affects GM loss in other regions and how it influences drinking behavior or relapse after treatment. The profile similarity index (PSI) combined with graph analysis allows to assess how GM loss in one region affects GM loss in regions connected to it, ie, GM connectivity. The PSI was used to describe the pattern of GM connectivity in 21 light drinkers (LDs) and in 54 individuals with AUD (ALC) early in abstinence. Effects of abstinence and relapse were determined in a subgroup of 36 participants after 3 months. Compared with LD, GM losses within the extended brain reward system (eBRS) at 1-month abstinence were similar between abstainers (ABST) and relapsers (REL), but REL had also GM losses outside the eBRS. Lower GM connectivities in ventro-striatal/hypothalamic and dorsolateral prefrontal regions and thalami were present in both ABST and REL. Between-networks connectivity loss of the eBRS in ABST was confined to prefrontal regions. About 3 months later, the GM volume and connectivity losses had resolved in ABST, and insula connectivity was increased compared with LD. GM losses and GM connectivity losses in REL were unchanged. Overall, prolonged abstinence was associated with a normalization of within-eBRS connectivity and a reconnection of eBRS structures with other networks. The re-formation of structural connectivities within and across networks appears critical for cognitive-behavioral functioning related to the capacity to maintain abstinence after outpatient treatment

Regulation of macrophage and granulocyte proliferation. Specificities of prostaglandin E and lactoferrin

Hemopoietic colony-forming cells committed to macrophage differentiation (M-CFC) are selectively and differentially inhibited by prostaglandin E (PGE). A hierarchy of sensitivity was observed among murine CFC stimulated by colony-stimulating factors (CSF) which differ in their ability to initiate proliferation of morphologically distinct colony types, or stimulated by CSF provided by macrophage feeder layers. Inhibition of macrophage colony formation to 50 percent levels occurred with PGE concentrations between 10(-8) and 10(-9) M, and was still evident at 10(-10) -10(-11) M PGE concentrations. The growth of mixed colonies containing both macrophages and neutrophils was less sensitive to the inhibitory effects of PGE, however, the monocytoid component of these colonies was reduced in the presence of PGE. Neutrophil progenitor cell proliferation was not influenced by PGE concentrations below 10(-6) M, regardless of time of addition of PGE, whereas clonal macrophage expansion, as well as clone size, was sensitive to inhibition by PGE when added as late as 3 d after culture initiation. Prostaglandin F(2α), was not inhibitory to colony formation. Experimental evidence for a selective role of macrophage PGE in the regulation of macrophage colony formation was directly provided by utilizing resident peritoneal macrophages as a source of CSF for bone marrow target cell overlays. Simultaneous morphological analysis of colonies proliferating in bilayer culture in response to increasing concentrations of macrophages, and direct measurements of PGE synthesized by an identical number of macrophages maintained in liquid culture demonstrate that a specific decline in macrophage colony formation occurs coincident with a linear increase in macrophage PGE synthesis. Inhibition of macrophage PGE synthesis by indomethacin results in the specific enhancement of macrophage colony formation. Furthermore, macrophage PGE synthesis is induced by CSF preparations with the selective capacity to differentially stimulate macrophage proliferation, but not by those which preferentially stimulate granulocyte colony formation. In comparison to the effects of PGE on M-CFC, polymorphonuclear granulocyte-derived lactoferrin (LF) reduces macrophage production of colony-stimulating activities for macrophage, mixed macrophage- neutrophil and neutrophil colony formation. The ability of LF to reduce macrophage PGE synthesis, presumably by decreasing CSF production, suggests that LF and PGE can interact in the control of macrophage and granulocyte proliferation

Dog owners are more likely to meet physical activity guidelines than people without at dog: An investigation of the association between dog ownership and physical activity levels in a UK community

Previous research suggests that dog owners are slightly more physically active than those without dogs, but have only studied one household member, and it is unclear whether time spent dog walking replaces other physical activity (PA). A survey of 191 dog owning adults (DO), 455 non-dog owning adults (NDO), and 46 children, living in 385 households in West Cheshire UK, was conducted in July-August 2015. Objective (accelerometer) validation occurred on a subset (n=28 adults). Survey PA outcomes were modelled using hierarchical logistic and linear multivariable regression modelling, accounting for clustering of participants in households. DO were far more likely than NDO to report walking for recreation (OR=14.35, 95% CI=5.77-35.79, P<0.001), and amongst recreational walkers walked for longer per week (RR=1.39, 95%CI=1.27-5.91, P<0.001). Other PA undertaken did not differ by dog ownership. The odds of DO meeting current physical activity guidelines of 150mins per week were four times greater than for NDO (OR=4.10, 95% CI=2.05-8.19, P<0.001). Children with dogs reported more minutes of walking (P=0.01) and free-time (unstructured) activity (P<0.01). Dog ownership is associated with more recreational walking and considerably greater odds of meeting PA guidelines. Policies regarding public spaces and housing should support dog ownership due to PA benefits

Influence of southern hemispheric biomass burning on midtropospheric distributions of nonmethane hydrocarbons and selected halocarbons over the remote South Pacific

Aircraft measurements of nonmethane hydrocarbons (NMHCs) and halocarbons were made over the remote South Pacific Ocean during late August-early October 1996 for NASA's Global Tropospheric Experiment (GTE) Pacific Exploratory Mission-Tropics A (PEM-Tropics A). This paper discusses the large-scale spatial distributions of selected trace gases encountered during PEM-Tropics A. The PEM-Tropics A observations are compared to measurements made over the southwestern pacific in early November 1995 as part of Aerosol Characterization Experiment (ACE 1). Continental pollution in the form of layers containing elevated levels of O3 was observed during a majority of PEM-Tropics flights, as well as during several ACE 1 flights. The chemical composition of these air masses indicates that they were not fresh and were derived from nonurban combustion sources. The substantial impact of biomass burning on the vertical structure of the South Pacific troposphere is discussed. Copyright 1999 by the American Geophysical Union

Overview of field-testing of the revised, draft South African Paediatric Food-Based Dietary Guidelines amongst mothers/caregivers of children aged 0–5 years in the Western Cape and Mpumalanga, South Africa

Background: This paper provides an overview of a series of studies undertaken to assess the appropriateness and understanding of the revised, draft South African Paediatric Food-Based Dietary Guidelines (SA-PFBDGs) amongst mothers/ caregivers of children aged 0–5 years. Previous exposure to guidelines with similar messages, barriers and enablers to following the guidelines were also assessed. Design: Qualitative methods were used to collect data from 38 focus-group discussions (isiXhosa = 11, Afrikaans = 11, English =10 and siSwati = 6) resulting in 268 participants. Setting: Breede Valley sub-district (Worcester), Stellenbosch Municipality (Stellenbosch, Pniel and Franschhoek) and Northern Metropole (Atlantis, Witsand, Du Noon and Blouberg), City of Cape Town, Western Cape province, as well as Ehlanzeni District (Kabokweni) in Mpumalanga province. Subjects: Mothers/caregivers older than 18 years who provided informed consent to participate. Results: The majority of participants had previous exposure to guidelines with similar messages to the SA-PFBDGs. Information sources included nurses, local clinics, family, friends and media. Possible barriers to following the guidelines included limited physical and financial access to resources; cultural/family practices, poor social support and time constraints. Outdated information, misconceptions, inconsistent messages and contrasting beliefs were evident. The vocabulary of some messages was not well understood. Education on infant and young child feeding and visual portrayal of the guidelines could aid understanding. Conclusion: A degree of rewording should be considered for improved understanding of the revised, draft SA-PFBDGs. Once adopted, the guidelines can be used to educate various stakeholders, including parents, caregivers, healthcare providers and educators, on the correct nutritional advice for children aged 0–5 years ensuring the healthy growth and development of young children in South Africa

Dosage Effects of Histamine-2 Receptor Antagonist on the Primary Prophylaxis of Non-Steroidal Anti-Inflammatory Drug (NSAID)-Associated Peptic Ulcers: A Retrospective Cohort Study

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Exploring the active site of the Streptococcus pneumoniae topoisomerase IV-DNA cleavage complex with novel 7,8-bridged fluoroquinolones.

As part of a programme of synthesizing and investigating the biological properties of new fluoroquinolone antibacterials and their targeting of topoisomerase IV from Streptococcus pneumoniae, we have solved the X-ray structure of the complexes of two new 7,8-bridged fluoroquinolones (with restricted C7 group rotation favouring tight binding) in complex with the topoisomerase IV from S. pneumoniae and an 18-base-pair DNA binding site-the E-site-found by our DNA mapping studies to bind drug strongly in the presence of topoisomerase IV (Leo et al. 2005 J. Biol. Chem. 280, 14 252-14 263, doi:10.1074/jbc.M500156200). Although the degree of antibiotic resistance towards fluoroquinolones is much lower than that of β-lactams and a range of ribosome-bound antibiotics, there is a pressing need to increase the diversity of members of this successful clinically used class of drugs. The quinolone moiety of the new 7,8-bridged agents ACHN-245 and ACHN-454 binds similarly to that of clinafloxocin, levofloxacin, moxifloxacin and trovofloxacin but the cyclic scaffold offers the possibility of chemical modification to produce interactions with other topoisomerase residues at the active site

Axion Protection from Flavor

The QCD axion fails to solve the strong CP problem unless all explicit PQ violating, Planck-suppressed, dimension n<10 operators are forbidden or have exponentially small coefficients. We show that all theories with a QCD axion contain an irreducible source of explicit PQ violation which is proportional to the determinant of the Yukawa interaction matrix of colored fermions. Generically, this contribution is of low operator dimension and will drastically destabilize the axion potential, so its suppression is a necessary condition for solving the strong CP problem. We propose a mechanism whereby the PQ symmetry is kept exact up to n=12 with the help of the very same flavor symmetries which generate the hierarchical quark masses and mixings of the SM. This "axion flavor protection" is straightforwardly realized in theories which employ radiative fermion mass generation and grand unification. A universal feature of this construction is that the heavy quark Yukawa couplings are generated at the PQ breaking scale.Comment: 16 pages, 2 figure

Muscle Glycogen Utilisation during an Australian Rules Football Game.

PURPOSE: To better understand the carbohydrate (CHO) requirement of Australian Football (AF) match play by quantifying muscle glycogen utilisation during an in-season AF match. METHODS: After a 24 h CHO loading protocol of 8 g/kg and 2 g/kg in the pre-match meal, two elite male forward players had biopsies sampled from m. vastus lateralis before and after participation in a South Australian Football League game. Player A (87.2kg) consumed water only during match play whereas player B (87.6kg) consumed 88 g CHO via CHO gels. External load was quantified using global positioning system technology. RESULTS: Player A completed more minutes on the ground (115 vs. 98 min) and covered greater total distance (12.2 vs. 11.2 km) than Player B, though with similar high-speed running (837 vs. 1070 m) and sprinting (135 vs. 138 m), respectively. Muscle glycogen decreased by 66% in Player A (Pre-: 656, Post-: 223 mmol∙kg-1 dw) and 24% in Player B (Pre-: 544, Post-: 416 mmol∙kg-1 dw), respectively. CONCLUSION: Pre-match CHO loading elevated muscle glycogen concentrations (i.e. >500 mmol.kg-1 dw), the magnitude of which appears sufficient to meet the metabolic demands of elite AF match play. The glycogen cost of AF match play may be greater than soccer and rugby and CHO feeding may also spare muscle glycogen use. Further studies using larger sample sizes are now required to quantify the inter-individual variability of glycogen cost of match play (including muscle and fibre-type specific responses) as well examine potential metabolic and ergogenic effects of CHO feeding

Use of Optical Genome Mapping to Detect Structural Variants in Neuroblastoma

\ua9 2023 by the authors.Background: Neuroblastoma is the most common extracranial solid tumour in children, accounting for 15% of paediatric cancer deaths. Multiple genetic abnormalities have been identified as prognostically significant in neuroblastoma patients. Optical genome mapping (OGM) is a novel cytogenetic technique used to detect structural variants, which has not previously been tested in neuroblastoma. We used OGM to identify copy number and structural variants (SVs) in neuroblastoma which may have been missed by standard cytogenetic techniques. Methods: Five neuroblastoma cell lines (SH-SY5Y, NBLW, GI-ME-N, NB1691 and SK-N-BE2(C)) and two neuroblastoma tumours were analysed using OGM with the Bionano Saphyr\uae instrument. The results were analysed using Bionano Access software and compared to previous genetic analyses including G-band karyotyping, FISH (fluorescent in situ hybridisation), single-nucleotide polymorphism (SNP) array and RNA fusion panels for cell lines, and SNP arrays and whole genome sequencing (WGS) for tumours. Results: OGM detected copy number abnormalities found using previous methods and provided estimates for absolute copy numbers of amplified genes. OGM identified novel SVs, including fusion genes in two cell lines of potential clinical significance. Conclusions: OGM can reliably detect clinically significant structural and copy number variations in a single test. OGM may prove to be more time- and cost-effective than current standard cytogenetic techniques for neuroblastoma