When Do Ring-Enhancing Brain Lesions Need to Be Biopsied, and Should They Be Treated Empirically First?

Other than acute cerebrovascular accidents, multiple ring-enhancing lesions are among the most common lesions encountered in neuroimaging. We herein describe the case of a 63-year-old diabetic man presenting with altered mental status, hyperglycaemia and community-acquired pneumonia who was found to have two ring-enhancing lesions involving the left frontal lobe and left basal ganglia. The lesions were biopsied to reveal positive fungal cultures and toxoplasma cysts. RPR titres returned reactive for non-treponemal antibodies and a suppressed CD4 count was found without evidence of HIV infection

The ‘Drug Bag’ method:Lessons from anthropological studies of antibiotic use in Africa and South-East Asia

Understanding the prevalence and types of antibiotics used in a given human and/or animal population is important for informing stewardship strategies. Methods used to capture such data often rely on verbal elicitation of reported use that tend to assume shared medical terminology. Studies have shown the category 'antibiotic' does not translate well linguistically or conceptually, which limits the accuracy of these reports. This article presents a 'Drug Bag' method to study antibiotic use (ABU) in households and on farms, which involves using physical samples of all the antibiotics available within a given study site. We present the conceptual underpinnings of the method, and our experiences of using this method to produce data about antibiotic recognition, use and accessibility in the context of anthropological research in Africa and South-East Asia. We illustrate the kinds of qualitative and quantitative data the method can produce, comparing and contrasting our experiences in different settings. The Drug Bag method produce accurate antibiotic use data as well as provide a talking point for participants to discuss antibiotic experiences. We propose it can help improve our understanding of antibiotic use in peoples' everyday lives across different contexts, and our reflections add to a growing conversation around methods to study ABU beyond prescriber settings, where data gaps are currently substantial

Frailty Screening and Detection of Geriatric Syndromes in Acute Inpatient Care: Impact on Hospital Length of Stay and 30-Day Readmissions

Background Frailty is prevalent in acute care and is associated with negative outcomes. While a comprehensive geriatric assessment to identify geriatric syndromes is recommended after identifying frailty, more evidence is needed to support this approach in the inpatient setting. This study examined the association between frailty and geriatric syndromes and their impact on outcomes in acutely admitted older adults. Methods A total of 733 individuals aged ≥65 years admitted to the General Surgery Service of a tertiary hospital were assessed for frailty using the Clinical Frailty Scale (CFS) and for geriatric syndromes using routine nursing admission assessments, including cognitive impairment, falls, incontinence, malnutrition, and poor oral health. Multinomial logistic regression and Cox regression were used to evaluate the associations between frailty and geriatric syndromes and their concomitant impact on hospital length of stay (LOS) and 30-day readmissions. Results Greater frailty severity was associated with an increased likelihood of geriatric syndromes. Individuals categorized as CFS 4–6 and CFS 7–8 with concomitant geriatric syndromes had 29% and 35% increased risks of a longer LOS, respectively. CFS 4–6 was significantly associated with functional decline (relative risk ratio =1.46; 95% confidence interval [CI], 1.03–2.07) and 30-day readmission (hazare ratio=1.78; 95% CI, 1.04–3.04), whereas these associations were not significant for CFS 7–8. Conclusions Geriatric syndromes in frail individuals can be identified from routine nursing assessments and represent a potential approach for targeted interventions following frailty identification. Tailored interventions may be necessary to achieve optimal outcomes at different stages of frailty. Further research is required to evaluate interventions for older adults with frailty in a wider hospital context

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multi-tissue integrative analysis of personal epigenomes

Evaluating the impact of genetic variants on transcriptional regulation is a central goal in biological science that has been constrained by reliance on a single reference genome. To address this, we constructed phased, diploid genomes for four cadaveric donors (using long-read sequencing) and systematically charted noncoding regulatory elements and transcriptional activity across more than 25 tissues from these donors. Integrative analysis revealed over a million variants with allele-specific activity, coordinated, locus-scale allelic imbalances, and structural variants impacting proximal chromatin structure. We relate the personal genome analysis to the ENCODE encyclopedia, annotating allele- and tissue-specific elements that are strongly enriched for variants impacting expression and disease phenotypes. These experimental and statistical approaches, and the corresponding EN-TEx resource, provide a framework for personalized functional genomics

α-Glucosidase Inhibitory Activity and Anti-Adipogenic Effect of Compounds from Dendrobium delacourii

Chemical investigation of Dendrobium delacourii revealed 11 phenolic compounds, and the structures of these compounds were determined by analysis of their NMR and HR-ESI-MS data. All compounds were investigated for their α-glucosidase inhibitory activity and anti-adipogenic properties. Phoyunnanin E (10) and phoyunnanin C (11) showed the most potent α-glucosidase inhibition by comparing with acarbose, which was used as a positive control. Kinetic study revealed the non-competitive inhibitors against the enzyme. For anti-adipogenic activity, densifloral B (3) showed the strongest inhibition when compared with oxyresveratrol (positive control). In addition, densifloral B might be responsible for the inhibition of adipocyte differentiation via downregulating the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT enhancer-binding protein alpha (C/EBPα), which are major transcription factors in adipogenesis

Contributors to the emerging investigators issue.

Biochemical Research MethodsChemistry, MultidisciplinaryNanoscience & NanotechnologySCI(E)0EDITORIAL MATERIAL182323-23331

Patterned delivery and expression of gene constructs into zebrafish embryos using microfabricated interfaces

We demonstrate a method which uses simple microfabrication and microfluidics to produce custom, shaped electroporators for the patterned delivery of foreign molecules into developing embryos. We show how these electroporators can be used to 'draw' two-dimensional patterns of tracer molecules, DNA and mRNA into the yolk and cells of zebrafish embryos (Danio rerio) at different stages of development. We demonstrate the successful delivery of patterns of Trypan Blue (normal dye), Texas Red (fluorescent dye), GFP-expressing DNA plasmids and GFP expressing mRNA constructs into both chorionated and dechorionated embryos. Both DNA and mRNA were expressed in the desired patterns subsequent to delivery. Square pulses of 10-20 V (0.20-0.40 kV/cm), 50-100 ms width were sufficient to create transient pores and introduce compounds from the late blastula period (3 hpf) to early pharyngula period (24 hpf) embryos. Using 24 hpf dechorionated embryos, we achieved a high survival of 91.3% and 89%, and a delivery efficiency of 38% and 50% for GFP-DNA and GFP-mRNA respectively. Lastly, we demonstrate the simultaneous delivery of different compounds into the developing embryo.close8

Rhesus Macaque Theta Defensins Suppress Inflammatory Cytokines and Enhance Survival in Mouse Models of Bacteremic Sepsis

Theta-defensins (θ-defensins) are macrocyclic antimicrobial peptides expressed in leukocytes of Old World monkeys. The peptides are broad spectrum microbicides in vitro and numerous θ-defensin isoforms have been identified in granulocytes of rhesus macaques and Olive baboons. Several mammalian α- and β-defensins, genetically related to θ-defensins, have proinflammatory and immune-activating properties that bridge innate and acquired immunity. In the current study we analyzed the immunoregulatory properties of rhesus θ-defensins 1–5 (RTDs 1–5). RTD-1, the most abundant θ-defensin in macaques, reduced the levels of TNF, IL-1α, IL-1β, IL-6, and IL-8 secreted by blood leukocytes stimulated by several TLR agonists. RTDs 1–5 suppressed levels of soluble TNF released by bacteria- or LPS-stimulated blood leukocytes and THP-1 monocytes. Despite their highly conserved conformation and amino acid sequences, the anti-TNF activities of RTDs 1–5 varied by as much as 10-fold. Systemically administered RTD-1 was non-toxic for BALB/c mice, and escalating intravenous doses were well tolerated and non-immunogenic in adult chimpanzees. The peptide was highly stable in serum and plasma. Single dose administration of RTD-1 at 5 mg/kg significantly improved survival of BALB/c mice with E. coli peritonitis and cecal ligation-and-puncture induced polymicrobial sepsis. Peptide treatment reduced serum levels of several inflammatory cytokines/chemokines in bacteremic animals. Collectively, these results indicate that the anti-inflammatory properties of θ-defensins in vitro and in vivo are mediated by the suppression of numerous proinflammatory cytokines and blockade of TNF release may be a primary effect