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Extracellular vesicles (EVs) can be loaded with therapeutic cargo and engineered for retention by specific body sites; therefore, they have great potential for targeted delivery of biomolecules to treat diseases. However, the pharmacokinetics and biodistribution of EVs in large animals remain relatively unknown, especially in primates. We recently reported that when cell culture-derived EVs are administered intravenously toMacaca nemestrina(pig-tailed macaques), they differentially associate with specific subsets of peripheral blood mononuclear cells (PBMCs). More than 60% of CD20+B cells were observed to associate with EVs for up to 1 hr post-intravenous administration. To investigate these associations further, we developed anex vivomodel of whole blood collected from healthy pig-tailed macaques. Using thisex vivosystem, we found that labeled EVs preferentially associate with B cells in whole blood at levels similar to those detectedin vivo. This study demonstrates thatex vivoblood can be used to study EV-blood cell interactions.

To catalyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research, including development of novel interventive and preventive strategies, the progression of disease was characterized in a robust coronavirus disease 2019 (COVID-19) animal model. In this model, male and female golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 USA-WA1/2020. Groups of inoculated and mock-inoculated uninfected control animals were euthanized at 2, 4, 7, 14, and 28 days after inoculation to track multiple clinical, pathology, virology, and immunology outcomes. SARS-CoV-2-inoculated animals consistently lost body weight during the first week of infection, had higher lung weights at terminal time points, and developed lung consolidation per histopathology and quantitative image analysis measurements. High levels of infectious virus and viral RNA were reliably present in the respiratory tract at days 2 and 4 after inoculation, corresponding with widespread necrosis and inflammation. At day 7, when the presence of infectious virus was rare, interstitial and alveolar macrophage infiltrates and marked reparative epithelial responses (type II hyperplasia) dominated in the lung. These lesions resolved over time, with only residual epithelial repair evident by day 28 after inoculation. The use of quantitative approaches to measure cellular and morphologic alterations in the lung provides valuable outcome measures for developing therapeutic and preventive interventions for COVID-19 using the hamster COVID-19 model.

The thermoresponsive behavior of a hydroxypropylmethylcellulose (HPMC) sample in aqueous solutions has been studied by a powerful combination of characterization tools, including rheology, turbidimetry, cryogenic transmission electron microscopy (cryoTEM), light scattering, small-angle neutron scattering (SANS), and small-angle X-ray scattering (SAXS). Consistent with prior literature, solutions with concentrations ranging from 0.3 to 3 wt % exhibit a sharp drop in the dynamic viscoelastic moduli G' and G″ upon heating near 57 °C. The drop in moduli is accompanied by an abrupt increase in turbidity. All the evidence is consistent with this corresponding to liquid-liquid phase separation, leading to polymer-rich droplets in a polymer-depleted matrix. Upon further heating, the moduli increase, and G' exceeds G″, corresponding to gelation. CryoTEM in dilute solutions reveals that HPMC forms fibrils at the same temperature range where the moduli increase. SANS and SAXS confirm the appearance of fibrils over a range of concentration, and that their average diameter is ca. 18 nm; thus gelation is attributable to formation of a sample-spanning network of fibrils. These results are compared in detail with the closely related and well-studied methylcellulose (MC). The HPMC fibrils are generally shorter, more flexible, and contain more water than with MC, and the resulting gel at high temperatures has a much lower modulus. In addition to the differences in fibril structure, the key distinction between HPMC and MC is that the former undergoes liquid-liquid phase separation prior to forming fibrils and associated gelation, whereas the latter forms fibrils first. These results and their interpretation are compared with the prior literature, in light of the relatively recent discovery of the propensity of MC and HPMC to self-assemble into fibrils on heating.

Although rare, hypertrophic cardiomyopathy (HCM) with midventricular obstruction is often associated with severe symptoms and complications. None of the existing HCM animal models display this particular phenotype. Our group developed a mouse line that overexpresses the ErbB2 receptor (ErbB2(tg)) in cardiomyocytes; we previously showed that the ErbB2 receptor induces cardiomyocyte hypertrophy, myocyte disarray, and fibrosis compatible with HCM. In the current study, we sought to further echocardiographically characterize the ErbB2(tg) mouse line as a model of HCM. Compared with their wild-type littermates, ErbB2(tg) mice show increased left ventricular (LV) mass, concentric LV hypertrophy, and papillary muscle hypertrophy. This hypertrophy was accompanied by diastolic dysfunction, expressed as reduced E:A ratio, prolonged deceleration time, and elevated E:e' ratio. In addition, ErbB2(tg) mice consistently showed midcavity obstruction with elevated LV gradients, and the flow profile revealed a prolonged pressure increase and a delayed peak, indicating dynamic obstruction. The ejection fraction was increased in ErbB2(tg) mice, due to reduced end-diastolic and end-systolic LV volumes. Furthermore, systolic radial strain and systolic radial strain rate but not systolic circumferential strain and longitudinal strain were decreased in ErbB2(tg) compared with wild-type mice. In conclusion, the phenotype of the ErbB2(tg) mouse model is consistent with midventricular HCM in many important aspects, including massive LV hypertrophy, diastolic dysfunction, and midcavity obstruction. This pattern is unique for a small animal model, suggesting that ErbB2(tg) mice may be well suited for research into the hemodynamics and treatment of this rare form of HCM.

Previous research suggests that a woman's past experiences of being parented will have a significant influence on how she parents her own children. This study, reported by Amanda Maxwell, Julie Proctor and Linda Hammond, aimed to explore young care-leaving mothers' experiences of motherhood, focusing on their experience of themselves as mothers, their relationship with their child and their understanding of their child's experiences. Six mothers were interviewed who had spent time in care and were teenagers at the time of the birth of their child. They also completed diaries of their experiences over a two-week period. Data were analysed using interpretative phenomenological analysis (IPA) and super-ordinate themes were identified. These themes were represented as dialectical positions and included: the ideal and reality; motherhood as building positive views of self and other, but also highlighting vulnerability; identification with her child but also feeling taken over by him or her; and external world as needed but also unwanted and destabilising. These results are discussed in relation to existing literature, and practice and research implications are considered.

The efficacy of porphyrin binding to human serum albumin (HSA) is critical to clinical use in photodynamic therapy (PDT). Several porphyrins were utilized to measure the effect of porphyrin structure on its binding to HSA. Two categories of porphyrins were utilized: porphyrins with a hydrophobic and hydrophilic side: Protoporphyrin IX (PPIX), Protoporphyrin IX dimethylester (PPIXDE), and Chlorin e6 (Ce6) and porphyrins with hydrophilic substituents on both sides: Hematoporphyrin IX (Hme), Hematoporphyrin IX dimethylester (HmeDE), and Deuteroporphyrin IX dimethylester (DPIXEG). The following methods were used for the analysis: Stern–Volmer quenching, fluorescence lifetimes, anisotropy, fluorescence binding, and homogeneous studies. The results indicate that PPIX, PPIXDE, and Ce6 bind to HSA efficiently, evidence that porphyrins bind strongly to HSA if they have a hydrophobic and hydrophilic side. Hme is thought to bind to HSA but likely to a lesser degree than the aforementioned three porphyrins. HmeDE and DPIXEG seem not to bind to HSA probably due to the lack of hydrophobic substituents.

A number of critical issues concerning the assessment of children with intellectual disabilities, including definitional problems, psychometric factors, and practical difficulties, are raised in this article. It is suggested that school counsellors and psychologists should consider these issues when assessing children with probable or known intellectual disabilities, particularly when using IQ tests. The use of adaptive scales as an additional means of defining and measuring intellectual disability is also examined. Although no ideal means of formally assessing children with intellectual disabilities is put forward, a range of concerns is explored and some suggestions for appropriate additions and caveats to present practice are proposed.

The response of canine insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) to moderate nutritional restriction followed by refeeding has not previously been studied in detail. The purpose of these studies was to examine the effects of nutritional restriction on the IGF system of adult dogs. Normal serum IGF values were established after validation of heterologous RIAs for measuring canine IGFs-I and -II. Canine serum IGFBP profiles were examined by Western ligand blotting (WLB), using radiolabelled recombinant human (rh) IGF-I as the ligand, and were found to be similar to those of other species. IGF-I and IGFBP-3 concentrations correlated with body weight, thus reflecting breed size as previously shown, whereas IGF-II concentrations did not. IGFBP-2 serum concentrations and band intensity on WLB were increased compared with normal human serum IGFBP-2. Overnight fasting had no effect on IGF or IGFBP concentrations, including IGFBP-1, nor did refeeding. Prolonged restriction to 56% and then 42.5% of maintenance energy requirements for 2 weeks decreased IGF-I concentrations by 20.4% and 32.7% respectively. Feeding of the same diet ad libitum for 2 weeks normalised IGF-I concentrations. There were no changes in IGF-II or insulin levels. Serum IGFBP-2 concentrations increased with 56% restriction of maintenance energy (P = 0.03). We conclude that serum IGF-I is potentially a useful marker of short-term change in nutritional status in the adult dog.

Nutritional modulation of insulin-like growth factors (IGF) and their binding proteins (IGFBP) is well established. The effect of nutritional restriction on the serum IGF/IGFBP system of adult cats was investigated to evaluate serum IGF-I as a biochemical marker of nutritional status. Assays for measuring feline serum IGF and IGFBP were validated and normal ranges established in a study population of 46 healthy nonobese adult cats. Serum concentrations of IGF-I and IGF-II correlated significantly with body weight (r = 0.75, P < 0. 0001 and r = 0.34, P < 0.03, respectively). Serum IGFBP profiles were similar to other species, including humans, dogs and guinea pigs. IGFBP-3 was the predominant binding protein reflecting IGF-I concentrations and body size. Serum IGFBP-2 concentrations were high relative to the normal human serum pool (NHS) control. Food withdrawal for 18 h followed by refeeding did not alter circulating IGF or IGFBP concentrations, including IGFBP-1, in nine cats. Short-term dietary restriction of nine adult cats to supply initially 56% (56%M) and then 42.5% (42.5%M) of calculated maintenance energy requirements for 14 d resulted in a significant weight loss (P < 0.01). However, serum IGF-I concentrations fell significantly (-51%, P < 0.01) only with 42.5%M restriction. Serum IGF-II, IGFBP, insulin and albumin concentrations were not altered during the study. We conclude that nutrition does modulate the adult feline IGF/IGFBP system, but to a lesser extent than in other species. Further evaluation is required before serum IGF-I can be used for the assessment of nutritional status in adult cats.

Eight gluten-sensitive Irish setters underwent a gluten challenge to investigate changes in the insulin-like growth factor (IGF) axis. In the first study, they were challenged with an acute intraduodenal administration of tryptic-peptic gluten digest and then maintained on dietary gluten for three months. In the second study, the challenge came solely from dietary gluten fed for three months. After the acute intraduodenal administration of gluten, serum IGF-I levels decreased signifilcantly by 21-8 per cent, (Pe0.01) on day 3 after challenge and then returned to normal. There was also a decrease (52.5 per cent, Pl0.03) in the levels of serum IGF-binding protein- 3 (IGFBP-3) until day 14 after challenge but they had returned to normal by day 28. In two dogs IGFBP-3 levels decreased through specific serum protease activity. There were no changes in serum IGF-I or IGFBP levels during the second study after the dietary gluten challenge alone, or in four non-gluten-sensitive beagles studied as controls during the acute intraduodenal/dietary gluten challenge.

This paper discusses the perceived seriousness and understanding of plagiarism by local and Asian international students in Australia, presenting new data from a study conducted at two Australian universities. In our study no differences were found between local and Asian students in ratings of perceived seriousness or understanding of plagiarism. However, significant negative relationships were found between both seriousness and understanding, and self-reported plagiarism rates. This suggested that as perceived seriousness and understanding decreased, rates of plagiarism increased. The importance of such findings in re-examining some commonly-held assumptions about cultural differences is discussed. It is suggested that most students demonstrate some difficulty understanding what constitutes plagiarism, highlighting the need for interventions that address knowledge of plagiarism and referencing skills.