Explore the vast range of titles available.

Cre recombinase and tdTomato expressed from a neutrophil-specific promoter allow highly specific genetic manipulation and labeling of neutrophils. Neutrophil granulocyte biology is a central issue of immunological research, but the lack of animal models that allow for neutrophil-selective genetic manipulation has delayed progress. By modulating the neutrophil-specific locus Ly6G with a knock-in allele expressing Cre recombinase and the fluorescent protein tdTomato, we generated a mouse model termed Catchup that exhibits strong neutrophil specificity. Transgene activity was found only in very few eosinophils and basophils and was undetectable in bone marrow precursors, including granulomonocytic progenitors (GMPs). Cre-mediated reporter-gene activation allowed for intravital two-photon microscopy of neutrophils without adoptive transfer. Homozygous animals were Ly6G deficient but showed normal leukocyte cellularity in all measured organs. Ly6G-deficient neutrophils were functionally normal in vitro and in multiple models of sterile or infectious inflammation in vivo . However, Cre-mediated deletion of FcγRIV in neutrophils reduced the cells' recruitment to immune-complex-mediated peritonitis, suggesting a cell-intrinsic role for activating Fc receptors in neutrophil trafficking.

Neuronal injury from ischemic stroke is aggravated by invading peripheral immune cells. Early infiltrates of neutrophil granulocytes and T-cells influence the outcome of stroke. So far, however, neither the timing nor the cellular dynamics of neutrophil entry, its consequences for the invaded brain area, or the relative importance of T-cells has been extensively studied in an intravital setting. Here, we have used intravital two-photon microscopy to document neutrophils and brain-resident microglia in mice after induction of experimental stroke. We demonstrated that neutrophils immediately rolled, firmly adhered, and transmigrated at sites of endothelial activation in stroke-affected brain areas. The ensuing neutrophil invasion was associated with local blood–brain barrier breakdown and infarct formation. Brain-resident microglia recognized both endothelial damage and neutrophil invasion. In a cooperative manner, they formed cytoplasmic processes to physically shield activated endothelia and trap infiltrating neutrophils. Interestingly, the systemic blockade of very-late-antigen-4 immediately and very effectively inhibited the endothelial interaction and brain entry of neutrophils. This treatment thereby strongly reduced the ischemic tissue injury and effectively protected the mice from stroke-associated behavioral impairment. Behavioral preservation was also equally well achieved with the antibody-mediated depletion of myeloid cells or specifically neutrophils. In contrast, T-cell depletion more effectively reduced the infarct volume without improving the behavioral performance. Thus, neutrophil invasion of the ischemic brain is rapid, massive, and a key mediator of functional impairment, while peripheral T-cells promote brain damage. Acutely depleting T-cells and inhibiting brain infiltration of neutrophils might, therefore, be a powerful early stroke treatment.

Polymorphonuclear neutrophils (PMN) mediate early immunity to infection but can also cause host damage if their effector functions are not controlled. Their lack or dysfunction is associated with severe health problems and thus the analysis of PMN physiology is a central issue. One prerequisite for PMN analysis is the availability of purified cells from primary organs. While human PMN are easily isolated from peripheral blood, this approach is less suitable for mice due to limited availability of blood. Instead, bone marrow (BM) is an easily available reservoir of murine PMN, but methods to obtain pure cells from BM are limited. We have developed a novel protocol allowing the isolation of highly pure untouched PMN from murine BM by negative immunomagnetic isolation using a complex antibody cocktail. The protocol is simple and fast (~1 h), has a high yield (5-10*10⁶ PMN per animal) and provides a purity of cells equivalent to positive selection (>80%). Most importantly, cells obtained by this method are non-activated and remain fully functional in vitro or after adoptive transfer into recipient animals. This method should thus greatly facilitate the study of primary murine PMN in vitro and in vivo.

Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease caused by the fungus Aspergillus fumigatus, and is a leading cause of invasive fungal infection-related mortality and morbidity in patients with hematological malignancies and bone marrow transplants. We developed and tested a novel probe for noninvasive detection of A. fumigatus lung infection based on antibody-guided positron emission tomography and magnetic resonance (immunoPET/MR) imaging. Administration of a [64Cu]DOTA-labeled A. fumigatus-specific monoclonal antibody (mAb), JF5, to neutrophil-depleted A. fumigatus-infected mice allowed specific localization of lung infection when combined with PET. Optical imaging with a fluorochrome-labeled version of the mAb showed colocalization with invasive hyphae. The mAb-based newly developed PET tracer [64Cu]DOTA-JF5 distinguished IPA from bacterial lung infections and, in contrast to [18F]FDG-PET, discriminated IPA from a general increase in metabolic activity associated with lung inflammation. To our knowledge, this is the first time that antibody-guided in vivo imaging has been used for noninvasive diagnosis of a fungal lung disease (IPA) of humans, an approach with enormous potential for diagnosis of infectious diseases and with potential for clinical translation.

Purpose To evaluate the effectiveness of food and nutrition regulations in developing healthy behaviors of young children, this study profiled the food and nutrient contribution of snacks, the foods and drinks consumed outside of main meals, in the diets of a sample of children between the ages of 3–5 years overall and in regulated child care (RCC) and home settings. Methods From a purposive sample of 44 RCC settings from across Nova Scotia, Canada, 19 agreed to participate in this study and with RCC directors’ approvals, invitations were sent to parents of enrolled children. Using a 4-day food record, foods and drinks consumed by 79 preschool aged children, were recorded by parents at home and by trained research assistants at RCC. The foods and drinks consumed during morning, afternoon and evening snack occasions coded by the What We Eat in America (WWEIA) categories and the provision of energy, sodium, fats, sugar and fiber were calculated. Descriptive statistics and independent t tests were used to determined differences between the foods and nutrients by where and when the snacks were consumed. Results On average, children consumed 2.3 snacks per day. Fruit, salty/sweet items and dairy items were predominately consumed as snacks. Average daily contributions from snacks were 29% of energy, 22.6% sodium, 27.6% saturated fat, 39.9% sugar and 31.3% dietary fiber. Significantly more variety of food categories and higher sodium and fiber snacks were consumed at RCC than home. Home morning snacks had significantly more sugar than RCC morning snacks. Conclusions The findings provide insight into the influences from RCC and home settings on snack intakes and the important role RCC food and nutrition regulations play in supporting healthy eating behaviors. Suggested recommendations are to de-emphasize the requirement for two food group servings for each snack at RCC, focus more on variety and nutrient dense snacks and encourage knowledge sharing between RCC and home environments to promote healthy children’s snacking behaviors.

Responsive feeding characterised by recognising and appropriately addressing children’s hunger and satiety signals, plays a key role in health. Despite children’s innate ability to self-regulate food intake, caregivers can override these cues, especially in child care settings. The study determined the effects of a 6-month coaching intervention on the responsive feeding environments of child care centres. CELEBRATE Feeding was a 6-month, coaching, pre-post intervention design conducted in eight child care centres across Nova Scotia and Prince Edward Island, Canada. Child care centres’ feeding environments and educator practices were observed using a modified Environment and Policy Assessment and Observation tool at baseline and follow-up in two rooms per centre (n = 16). Twenty-one responsive feeding components were scored from 0–3 (3 as best practice). The average centre scores were summed for an overall score ranging from 0–63 at each time point. Paired samples t-tests and Wilcoxon signed rank tests were conducted to assess the impact of the intervention on overall rooms’ and individual responsive feeding components’ scores. There was an increase in scores from baseline (M = 38.16, SD = 6.55) to follow-up (M = 45.75, SD = 5.87), t (15) = 4.91, P < 0.001. All but one score improved, where 3 of the 21 scores were significantly more responsive after the intervention after applying a Bonferroni correction (P < 0.002). The score with the greatest positive change was ‘Educators provide gentle comments or nudges towards feeding’, with a mean difference of 1.33, P < 0.001. The CELEBRATE Feeding coaching intervention was successful in improving responsive feeding practices and environments in child care settings.

Background: Teenage pregnancy rates are falling in many high-resource settings, but for those who do conceive, the socioeconomic and educational disadvantage that ensues is often long lasting and intergenerational. The adverse maternal and neonatal outcomes can be ameliorated through antenatal and postnatal care that attends to the special needs of this group. Objective: The aim of this article is to provide an overview of the social, obstetric and medical complications of teenage pregnancy and the role of the general practitioner (GP) in mitigating adverse outcomes. Discussion: Management and prevention of teenage pregnancy requires broad efforts that involve schools, health services and the community. The GP has a key role in providing supportive continuity of care that spans the antenatal and crucial postnatal periods.

Airborne fungal pathogens, predominantly Aspergillus fumigatus, can cause severe respiratory tract diseases. Here we show that in environments, fungal spores can already be decorated with nanoparticles. Using representative controlled nanoparticle models, we demonstrate that various nanoparticles, but not microparticles, rapidly and stably associate with spores, without specific functionalization. Nanoparticle-spore complex formation was enhanced by small nanoparticle size rather than by material, charge, or “stealth” modifications and was concentration-dependently reduced by the formation of environmental or physiological biomolecule coronas. Assembly of nanoparticle-spore surface hybrid structures affected their pathobiology, including reduced sensitivity against defensins, uptake into phagocytes, lung cell toxicity, and TLR/cytokine-mediated inflammatory responses. Following infection of mice, nanoparticle-spore complexes were detectable in the lung and less efficiently eliminated by the pulmonary immune defense, thereby enhancing A. fumigatus infections in immunocompromised animals. Collectively, self-assembly of nanoparticle-fungal complexes affects their (patho)biological identity, which may impact human health and ecology.

The vegetable/fruit intakes of a sample of children attending regulated childcare in Nova Scotia was assessed and compared by age groups (3 and 4-5 year olds) and by home and childcare environments. Seventy-nine children had 3-4-day food records and 58 had records from both environments. The data were coded by the 2007 (CFG) recommendations and the 2014 (CNF/CFG) Tiers. Descriptive statistics and tests of significance were determined. Overall, 56% of children met the CFG vegetable/fruit recommendations but the percentage of older children meeting recommendations was half that of the younger age group; a significant difference. Fruit and juice comprised 65% of vegetable/fruit intakes with more consumed at home. Vegetable/fruit items were mostly from the higher quality CNF/CFG Tiers but more of the lower quality items were consumed at home. The 4-5 year olds may not be increasing their vegetable/fruit intakes as the CFG recommends. While just over half of children met CFG vegetable/fruit recommendations, the vegetable/fruit items were mostly high quality; fruit and juice predominated. Identification of strategies to support increased vegetable/fruit intakes of children in both home and childcare environments is warranted.

Continuing care (CC) facilities have been impacted by a growing demand for services, insufficient resources for the provision of quality food and nutrition care, and, most recently, the COVID-19 pandemic. This study explored the roles and responsibilities of dietitians working in CC facilities in Nova Scotia (NS) before and after the COVID-19 first wave. Using ethics-approved questionnaires, the estimated 75 dietitians working in CC facilities in NS were surveyed in Fall 2019 and Fall 2020 about their roles and responsibilities. Twenty responded to the first questionnaire and 15 to the second. Analysis of data included simple statistical and qualitative description methods. The findings highlighted the complexities and challenges faced by these dietitians in the provision of resident nutrition care, overseeing foodservices, training staff and dietetic interns, and contributing to facility specific care committees before and after the COVID-19 first wave. There is a need to advocate for minimum standards for dietetic and foodservice funding in CC facilities based on higher acuity and complex care needs of residents and considering the multifaceted roles of dietitians in CC. Efforts to improve awareness about the roles of dietitians working in CC among resident families, other dietitians, and dietetic interns are also needed.