Obesity in adults: a 2022 adapted clinical practice guideline for Ireland

This Clinical Practice Guideline (CPG) for the management of obesity in adults in Ireland, adapted from the Canadian CPG, defines obesity as a complex chronic disease characterised by excess or dysfunctional adiposity that impairs health. The guideline reflects substantial advances in the understanding of the determinants, pathophysiology, assessment, and treatment of obesity. It shifts the focus of obesity management toward improving patient-centred health outcomes, functional outcomes, and social and economic participation, rather than weight loss alone. It gives recommendations for care that are underpinned by evidence-based principles of chronic disease management; validate patients' lived experiences; move beyond simplistic approaches of "eat less, move more" and address the root drivers of obesity. People living with obesity face substantial bias and stigma, which contribute to increased morbidity and mortality independent of body weight. Education is needed for all healthcare professionals in Ireland to address the gap in skills, increase knowledge of evidence-based practice, and eliminate bias and stigma in healthcare settings. We call for people living with obesity in Ireland to have access to evidence-informed care, including medical, medical nutrition therapy, physical activity and physical rehabilitation interventions, psychological interventions, pharmacotherapy, and bariatric surgery. This can be best achieved by resourcing and fully implementing the Model of Care for the Management of Adult Overweight and Obesity. To address health inequalities, we also call for the inclusion of obesity in the Structured Chronic Disease Management Programme and for pharmacotherapy reimbursement, to ensure equal access to treatment based on health-need rather than ability to pay

Iron deficiency in healthy, term infants aged five months, in a pediatric outpatient clinic: a prospective study

Abstract Background Iron deficiency (ID) is prevalent in Malaysian children. The incidence of ID in infants under 6 months of age is unknown. Our aim was to determine the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) in healthy, term infants aged below 6 months in our hospital population. Methods A prospective longitudinal pilot study of mother-infant pairs was conducted on infants receiving routine immunizations in a mother and child clinic at a university hospital, in Kuala Lumpur, Malaysia. Mothers completed standardized questionnaires at 3- and 5-month postnatal visits. Maternal and infant full blood count, ferritin, and C-reactive protein (CRP) levels were measured at 3 months and for the infants repeated at 5 months. Infant anthropometric measurements were obtained at both visits. We conducted a univariate analysis to identify factors associated with ID and IDA. Results Altogether, 91 mother-infant pairs were enrolled, with 88 completing the study. No infant had ID or IDA at 3 months; the lowest ferritin level was 16.6 µg/L. At 5 months, 5.9% (5/85) of infants had ID, and 2.4% (2/85) had IDA. Median (interquartile range) infant ferritin levels significantly declined from 113.4 (65.0–183.6) µg/L at 3 months to 50.9 (29.2–70.4) µg/L at 5 months, p < 0.001. Exclusive breastfeeding until 3 or 5 months was significantly associated with ID at 5 months (p = 0.020, and p = 0.008, respectively) on univariate analysis. The drop in ferritin between 3–5 months was significantly associated with weight and length gains between 0–3 months (p = 0.018, p = 0.009, respectively). Altogether, 14.3% of infants exclusively breastfed until 5 months developed ID. At 5 months, 3.4% of infants were underweight, 1.1% stunted, and 10.2% wasted. Conclusions In exclusively breastfed term infants, ID occurred by 5 months. Early introduction of iron-rich foods should be considered in exclusively breastfed babies. A high prevalence of wasting suggests a calorie deficit in this population and will lead to stunting if not addressed

New insights into ocean sunfish (mola mola) abundance and seasonal distribution in the northeast atlantic

The ocean sunfish, Mola mola, is the largest teleost fish in the world. Despite being found in all oceans of the world, little is known about its abundance and factors driving its distribution. In this study we provide the first abundance estimates for sunfish in offshore waters in the northeast Atlantic and the first record of extensive sunfish presence in these waters year-round. Abundance estimates and predictive distributions for sunfish in approximately 300,000 km(2) of the northeast Atlantic were derived from large scale offshore aerial surveys in 2015-2016 using distance sampling techniques. Generalized additive models of sunfish density were fitted to survey data from 17,360 km of line transect effort resulting in minimum abundance estimates of 12,702 (CI: 9,864-16,357) in the summer (Density = 0.043 ind/ km(2)) and 8,223 individuals (CI: 6,178-10,946) (Density = 0.028 ind/ km(2)) in the winter. Density surface models predicted seasonal shifts in distribution and highlighted the importance of the mixed layer depth, possibly related to thermoregulation following deep foraging dives. The abundance estimate and estimated daily consumption of 2,600 tonnes of jellyfish in the northeast Atlantic highlights the need to re-assess the importance of this species in the pelagic ecosystem, and its role in top-down control of jellyfish blooms

Microlearning and online simulation-based virtual consultation training module for the undergraduate medical curriculum – a preliminary evaluation

Abstract Background Virtual consultation is a synchronous mode of telemedicine provided remotely via information and communication technology. The projected growth of digitalization in healthcare delivery, however, necessitates medical student training in virtual consultation (VC) to ensure safe and effective patient care. This study describes the implementation and preliminary evaluation of a competency-based VC training module for undergraduate medical students. Methods A newly developed six-week VC module was implemented online through asynchronous microlearning and synchronous simulation-based experiential learning modalities. Clinical students in years 4 and 5 and fresh graduates, who had not started pre-registration house officer or residency programmes, were invited to participate. Training outcomes using checklist-based video-recorded assessments of VC encounters between medical students and simulated patients were compared. Each video was independently assessed by two facilitators trained in VC teaching and assessment, using a direct observed virtual consultation skills checklist derived from established VC competencies. The participants completed course evaluations electronically as additional outcome measures. Results Fifty-two clinical phase medical students and alumni completed both the instructional and practical phases of this module. Altogether, 45 (95.7%) students found the module beneficial, and 46 (95.9%) reported increased self-efficacy for conducting VC. In total, 46 (95.9%) students would recommend the course to others. Post-test results showed a significant increase in the students’ abilities to conduct a VC (t-test = 16.33, p < 0.05). Conclusion Microlearning and simulation-based sessions were effective instructional delivery modalities for undergraduate medical students in their attainment of VC competencies

Vector-free intracellular delivery by reversible permeabilization

Despite advances in intracellular delivery technologies, efficient methods are still required that are vector-free, can address a wide range of cargo types and can be applied to cells that are difficult to transfect whilst maintaining cell viability. We have developed a novel vector-free method that uses reversible permeabilization to achieve rapid intracellular delivery of cargos with varying composition, properties and size. A permeabilizing delivery solution was developed that contains a low level of ethanol as the permeabilizing agent. Reversal of cell permeabilization is achieved by temporally and volumetrically controlling the contact of the target cells with this solution. Cells are seeded in conventional multi-well plates. Following removal of the supernatant, the cargo is mixed with the delivery solution and applied directly to the cells using an atomizer. After a short incubation period, permeabilization is halted by incubating the cells in a phosphate buffer saline solution that dilutes the ethanol and is non-toxic to the permeabilized cells. Normal culture medium is then added. The procedure lasts less than 5 min. With this method, proteins, mRNA, plasmid DNA and other molecules have been delivered to a variety of cell types, including primary cells, with low toxicity and cargo functionality has been confirmed in proof-of-principle studies. Co-delivery of different cargo types has also been demonstrated. Importantly, delivery occurs by diffusion directly into the cytoplasm in an endocytic-independent manner. Unlike some other vector-free methods, adherent cells are addressed in situ without the need for detachment from their substratum. The method has also been adapted to address suspension cells. This delivery method is gentle yet highly reproducible, compatible with high throughput and automated cell-based assays and has the potential to enable a broad range of research, drug discovery and clinical applications

Using tagging data and aerial surveys to incorporate availability bias in the abundance estimation of blue sharks (Prionace glauca).

There is worldwide concern about the status of elasmobranchs, primarily as a result of overfishing and bycatch with subsequent ecosystem effects following the removal of top predators. Whilst abundant and wide-ranging, blue sharks (Prionace glauca) are the most heavily exploited shark species having suffered marked declines over the past decades, and there is a call for robust abundance estimates. In this study, we utilized depth data collected from two blue sharks using pop-up satellite archival tags, and modelled the proportion of time the sharks were swimming in the top 1-meter layer and could therefore be detected by observers conducting aerial surveys. The availability models indicated that the tagged sharks preferred surface waters whilst swimming over the continental shelf and during daytime, with a model-predicted average proportion of time spent at the surface of 0.633 (SD = 0.094) for on-shelf, and 0.136 (SD = 0.075) for off-shelf. These predicted values were then used to account for availability bias in abundance estimates for the species over a large area in the Northeast Atlantic, derived through distance sampling using aerial survey data collected in 2015 and 2016 and modelled with density surface models. Further, we compared abundance estimates corrected with model-predicted availability to uncorrected estimates and to estimates that incorporated the average time the sharks were available for detection. The mean abundance (number of individuals) corrected with modelled availability was 15,320 (CV = 0.28) in 2015 and 11,001 (CV = 0.27) in 2016. Depending on the year, these estimates were ~7 times higher compared to estimates without the bias correction, and ~3 times higher compared to the abundances corrected with average availability. When the survey area contains habitat heterogeneity that may affect surfacing patterns of animals, modelling animals' availability provides a robust alternative to correcting for availability bias and highlights the need for caution when applying "average" correction factors

Cell functionality and intracellular targeting.

<p>(A) Alexa Fluor^® 488-labelled tyramide substrate demonstrated activity and localization of HRP in CHO cells following delivery of HRP. (B) Increasing production of fluorescent DCF product with increasing dose of HRP delivered into CHO cells compared with cells where HRP was delivered by pipette. (C) GFP expression following delivery of GFP mRNA. (D) Cell viability remained above 75% up to 168hr post-delivery. (E) Up to 3 doses of GFP mRNA (4 μg) were delivered. GFP expression was analyzed 24 hr after the final dose. (F) Confocal microscopy image illustrates co-delivery to A549 cells: DAPI (300 nM), Mitotracker Red (50 μM) and Phalloidin-Alexa488 (0.33 μM) correspond to blue nuclei, red mitochondria and green actin filaments, respectively. <i>n</i> = 3, data are depicted as the mean ± the standard deviation. (HRP = horseradish peroxidase; DCF = dichlorofluorescein; GFP = green fluorescent protein; DAPI = 4',6-diamidino-2-phenylindole).</p

Delivery and viability compared with electroporation.

<p>Comparison of delivery efficiency (using 10kDa dextran-Alexa488) and cell viability and survival (using propidium iodide exclusion) for (A) the reversible permeabilization method and (B) electroporation. (C) The transfection score defined as (transfected cells/ total cells)x(viable cells/ total cells) for the two methods). <i>n</i> = 3, data are depicted as the mean ± standard deviation.</p

Cell-independent delivery.

<p>(A) Delivery of 3 μM 10 kDa dextran-Alexa488 to primary human fibroblasts and primary human MSC. (B) Efficiency of delivery was quantified by flow cytometry at 2 hr post-delivery. (C) Delivery of BSA-FITC to U266 and Jurkat suspension cells. (D) Efficiency of delivery was quantified by flow cytometry at 2 hr post-delivery. All photomicrographs are 10x magnification. <i>n</i> = 3, data are depicted as the mean ± the standard deviation. (MSC = mesenchymal stem cells; BSA-FITC = bovine serum albumin-fluorescein isothiocyanate).</p

Testing mechanisms of cargo uptake and subsequent membrane resealing.

<p>(A) Time course of uptake of 10 kDa dextran-Alexa488 into A549 cells analyzed by fluorescence microscopy consistent with simple diffusion post-delivery (10x mag.). (B) In A549 cells the uptake of EGFP mRNA was not inhibited either by pretreatment with Dynasore or chloropromazine to inhibit clathrin-mediated endocytosis or Nystatin or EIPA to inhibit caveolar-mediated endocytosis and micropinocytosis. (C) Lipofectamine 2000 was used as a positive control for endocytosis-mediated delivery. EGFP expression was reduced in lipofected cells treated with Dynasore. (D) PI uptake was analyzed by flow cytometry and the data indicate that the cells remain permeable to PI for up to 6 min post-treatment but then reseal and prevent uptake thereafter. <i>n</i> = 3, data are depicted as the mean ± standard deviation. (EIPA = 5-(N-Ethyl-N-isopropyl)amiloride; EGFP = enhanced green fluorescent protein; PI = propidium iodide; PBS = phosphate buffered saline).</p