Comparison of Ultrastructural Cytotoxic Effects of Carbon and Carbon/Iron Particulates on Human Monocyte-Derived Macrophages

In this study, we tested the hypothesis that the presence of iron in carbon particulates enhances ultrastructural perturbation in human monocyte-derived macrophages (MDMs) after phagocytosis. We used 1-μm synthetic carbon-based particulates, designed to simulate environmental particulates of mass median aerodynamic diameter ≤ 2.5 μm (PM(2.5)). Cultures of human MDMs or T-lymphocytes (as a nonphagocytic control) were exposed to carbon or carbon/iron particulates for various time periods and examined by transmission electron microscopy for ultrastructural changes. T-cells failed to internalize either of the particulates and showed no organelle or nuclear changes. Conversely, MDMs avidly phagocytized the particulates. MDMs treated with C particulates exhibited morphologic evidence of macrophage activation but no evidence of lysis of organelles. In contrast, MDMs treated with C/Fe particulates exhibited coalescence of particulate-containing lysosomes. This phenomenon was not observed in the case of C particulates. By 24 hr there was a tendency of the C/Fe particulates to agglomerate into loose or compact clusters. Surrounding the compact C/Fe agglomerates was a uniform zone of nearly total organelle lysis. The lytic changes diminished in proportion to the distance from the agglomerate. In such cells, the nucleus showed loss of chromatin. Although C particles induced no detectable oxidative burst on treated MDMs, C/Fe particles induced a nearly 5-fold increase in the extracellular oxidative burst by treated MDMs compared with untreated controls. Iron bound to C particles catalyzed the decomposition of hydrogen peroxide to generate hydroxyl radicals. Results of these studies suggest that, among particulates of similar size, biologic activity can vary profoundly as a function of particulate physicochemical properties

Peer observation of teaching: A decoupled process

This article details the findings of research into the academic teaching staff experience of peer observation of their teaching practice. Peer observation is commonly used as a tool to enhance a teacher’s continuing professional development. Research participants acknowledged its ability to help develop their teaching practice, but they also reported that it could operate superficially as a tick box exercise, that its outcomes were frequently decoupled from formal staff development processes, and that its purpose and usefulness therefore seemed unclear. This article argues that the presence of decoupling reinforces the need to account for structural factors that can interact with peer observation of teaching to ensure it is a meaningful exercise for all teaching staff. It concludes that the published academic literature is perhaps guilty of overplaying the role of personal choice and individual tutor characteristics when addressing the complex issue that is staff disengagement with peer observation of teaching

Characteristics of Cognitive Behavioral Therapy for Older Adults Living in Residential Care: Protocol for a Systematic Review

Background: The prevalence rates of depressive and anxiety disorders are high in residential aged care settings. Older adults in such settings might be prone to these disorders because of losses associated with transitioning to residential care, uncertainty about the future, as well as a decline in personal autonomy, health, and cognition. Cognitive behavioral therapy (CBT) is efficacious in treating late-life depression and anxiety. However, there remains a dearth of studies examining CBT in residential settings compared with community settings. Typically, older adults living in residential settings have higher care needs than those living in the community. To date, no systematic reviews have been conducted on the content and the delivery characteristics of CBT for older adults living in residential aged care settings. Objective: The objective of this paper is to describe the systematic review protocol on the characteristics of CBT for depression and/or anxiety for older adults living in residential aged care settings. Methods: This protocol was developed in compliance with the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Studies that fulfill the inclusion criteria will be identified by systematically searching relevant electronic databases, reference lists, and citation indexes. In addition, the PRISMA flowchart will be used to record the selection process. A pilot-tested data collection form will be used to extract and record data from the included studies. Two reviewers will be involved in screening the titles and abstracts of retrieved records, screening the full text of potentially relevant reports, and extracting data. Then, the delivery and content characteristics of different CBT programs of the included studies, where available, will be summarized in a table. Furthermore, the Downs and Black checklist will be used to assess the methodological quality of the included studies. Results: Systematic searches will commence in May 2018, and data extraction is expected to commence in July 2018. Data analyses and writing will happen in October 2018. Conclusions: In this section, the limitations of the systematic review will be outlined. Clinical implications for treating late-life depression and/or anxiety, and implications for residential care facilities will be discussed

Phylogenetic Placement of Exact Amplicon Sequences Improves Associations with Clinical Information

Janssen S, McDonald D, Gonzalez A, et al. Phylogenetic Placement of Exact Amplicon Sequences Improves Associations with Clinical Information. mSystems. 2018;3(3):e00021-18

Metformin reduces airway glucose permeability and hyperglycaemia-induced Staphylococcus aureus load independently of effects on blood glucose

Background Diabetes is a risk factor for respiratory infection, and hyperglycaemia is associated with increased glucose in airway surface liquid and risk of Staphylococcus aureus infection. Objectives To investigate whether elevation of basolateral/blood glucose concentration promotes airway Staphylococcus aureus growth and whether pretreatment with the antidiabetic drug metformin affects this relationship. Methods Human airway epithelial cells grown at air–liquid interface (±18 h pre-treatment, 30 μM–1 mM metformin) were inoculated with 5×105 colony-forming units (CFU)/cm2 S aureus 8325-4 or JE2 or Pseudomonas aeruginosa PA01 on the apical surface and incubated for 7 h. Wild-type C57BL/6 or db/db (leptin receptor-deficient) mice, 6–10 weeks old, were treated with intraperitoneal phosphate-buffered saline or 40 mg/kg metformin for 2 days before intranasal inoculation with 1×107 CFU S aureus. Mice were culled 24 h after infection and bronchoalveolar lavage fluid collected. Results Apical S aureus growth increased with basolateral glucose concentration in an in vitro airway epithelia–bacteria co-culture model. S aureus reduced transepithelial electrical resistance (RT) and increased paracellular glucose flux. Metformin inhibited the glucose-induced growth of S aureus, increased RT and decreased glucose flux. Diabetic (db/db) mice infected with S aureus exhibited a higher bacterial load in their airways than control mice after 2 days and metformin treatment reversed this effect. Metformin did not decrease blood glucose but reduced paracellular flux across ex vivo murine tracheas. Conclusions Hyperglycaemia promotes respiratory S aureus infection, and metformin modifies glucose flux across the airway epithelium to limit hyperglycaemia-induced bacterial growth. Metformin might, therefore, be of additional benefit in the prevention and treatment of respiratory infection

Suitability of simple human immunodeficiency virus rapid tests in clinical trials in community-based clinic settings

The suitability and accuracy of using simple human immunodeficiency virus (HIV) rapid (SR) tests in community-based clinics in northwest Tanzania were determined to assess eligibility for participation in clinical trials. The HIV rapid and ELISA test results for 789 women aged 16 to 54 who were screened for two clinical trials of HIV prevention were compared. Women were offered voluntary HIV counseling and testing (VCT) at screening; those who accepted were tested with the Abbott Determine and Trinity Biotech Capillus SR tests in parallel. The results were confirmed by two parallel HIV enzyme-linked immunosorbent assay (ELISA) tests (Abbott Murex HIV Ag/Ab combination and Vironostika Uniform II HIV Ag/Ab) to determine eligibility. Positive samples for any of the four assays were confirmed by a line immunoassay and p24 testing. The parallel SR tests had high concordance (96.2%) with the parallel ELISA algorithm. The sensitivities of the SR tests were 98.6% for Capillus (95% confidence interval [CI], 95.1 to 99.8%), 99.3% for Determine (95% CI, 96.2 to 100%), and 98.6% for the parallel SR (95% CI, 95.1 to 99.8%). The specificities were 99.7% for Capillus (95% CI, 98.9 to 100%), 99.7% for Determine (95% CI, 98.9 to 100%), and 100% for the parallel SR (95% CI, 99.4 to 100%). SR tests are suitable for use in community-based clinical research settings to assess eligibility both for trial participation and for the provision of on-site VCT services. Copyrigh

Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization

Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epidermal-growth-factor-like-domains 8 (MEGF8), which exhibits substantial clinical overlap with Carpenter syndrome but is frequently associated with abnormal left-right patterning. We describe five affected individuals with similar dysmorphic facies, and three of them had either complete situs inversus, dextrocardia, or transposition of the great arteries; similar cardiac abnormalities were previously identified in a mouse mutant for the orthologous Megf8. The mutant alleles comprise one nonsense, three missense, and two splice-site mutations; we demonstrate in zebrafish that, in contrast to the wild-type protein, the proteins containing all three missense alterations provide only weak rescue of an early gastrulation phenotype induced by Megf8 knockdown. We conclude that mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members. We did not observe any subject with biallelic loss-of function mutations, suggesting that some residual MEGF8 function might be necessary for survival and might influence the phenotypes observed

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

<b>Background</b> Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.<p></p> <b>Methods and findings</b> The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.<p></p> <b>Conclusions</b> Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems