Skin as the target for allergy prevention and treatment.

The fact that genetic and environmental factors could trigger disruption of the epithelial barrier and subsequently initiate a TH2 inflammatory cascade conversely proposes that protecting the same barrier and promoting adequate interactions with other organs, such as the gut, may be crucial for lowering the risk and preventing atopic diseases, particularly, food allergies. In this review, we provide an overview of structural characteristics that support the epithelial barrier hypothesis in patients with atopic dermatitis, including the most relevant filaggrin gene mutations, the recent discovery of the role of the transient receptor potential vanilloid 1, and the role involvement of the microbiome in healthy and damaged skin. We present experimental and human studies that support the mechanisms of allergen penetration, particularly the dual allergen exposure and the outside-in, inside-out, and outside-inside-outside hypotheses. We discuss classic skin-targeted therapies for food allergy prevention, including moisturizers, steroids, and topical calcineurin inhibitors, along with pioneering trials proposed to change their current use (Prevention of Allergy via Cutaneous Intervention and Stopping Eczema and ALlergy). We provide an overview of the novel therapies that enhance the skin barrier, such as probiotics and prebiotics topical application, read-through drugs, direct and indirect FLG replacement, and interleukin and janus kinases inhibitors. Last, we discuss the newer strategies for preventing and treating food allergies in the form of epicutaneous immunotherapy and the experimental use of single-dose of adeno-associated virus vector gene immunotherapy.

An abnormal finding in the third trimester.

A healthy woman presented with an antepartum haemorrhage at 35/40 during a low-risk pregnancy with normal antenatal bloods and anomaly scan at 20/40 gestation. Following an abnormal ultrasound (USS), the baby was delivered by emergency C-section. A male infant was born in good condition but admitted to the neonatal unit for monitoring. Examination revealed global hypotonia, a weak uncoordinated suck and absent Moro reflex. He had widened sagittal sutures and a large posterior fontanelle. The remainder of the examination was unremarkable. Abnormal bloods are shown in table 1 .

Facilitators and barriers to teaching undergraduate medical students in general practice.

CONTEXT: Globally, primary health care is facing workforce shortages. Longer and higher-quality placements in primary care increase the likelihood of medical students choosing this specialty. However, the recruitment and retention of community primary care teachers are challenging. Relevant research was predominantly carried out in the 1990s. We seek to understand contemporary facilitators and barriers to general practitioner (GP) engagement with undergraduate education. Communities of practice (CoP) theory offers a novel conceptualisation, which may be pertinent in other community-based teaching settings. METHODS: Semi-structured interviews were undertaken with 24 GP teachers at four UK medical schools. We purposively sampled GPs new to teaching, established GP teachers and GPs who had recently stopped teaching. We undertook NVivo-assisted deductive and inductive thematic analysis of transcripts. We used CoP theory to interpret data. RESULTS: Communities of practice theory illustrated that teachers negotiate membership of three CoPs: (i) clinical practice; (ii) the medical school, and (iii) teaching. The delivery of clinical care and teaching may be integrated or exist in tension. This can depend upon the positioning of the teaching and teacher as central or peripheral to the clinical CoP. Remuneration, workload, space and the expansion of GP trainee numbers impact on this. Teachers did not identify strongly as members of the medical school or a teaching community. Perceptions of membership were affected by medical school communication and support. The findings demonstrate gaps in medical school recruitment. CONCLUSIONS: This research demonstrates the marginalisation of primary care-based teaching and proposes a novel explanation rooted in CoP theory. Concepts including identity and membership may be pertinent to other community-based teaching settings. We recommend that medical schools review and broaden recruitment methods. Teacher retention may be improved by optimising the interface between medical schools and teachers, fostering a teaching community, increasing professional rewards for teaching involvement and altering medical school expectations of learning in primary care.

Enhancing voluntary imitation through attention and motor imagery.

Action observation activates brain areas involved in performing the same action and has been shown to increase motor learning, with potential implications for neurorehabilitation. Recent work indicates that the effects of action observation on movement can be increased by motor imagery or by directing attention to observed actions. In voluntary imitation, activation of the motor system during action observation is already increased. We therefore explored whether imitation could be further enhanced by imagery or attention. Healthy participants observed and then immediately imitated videos of human hand movement sequences, while movement kinematics were recorded. Two blocks of trials were completed, and after the first block participants were instructed to imagine performing the observed movement (Imagery group, N = 18) or attend closely to the characteristics of the movement (Attention group, N = 15), or received no further instructions (Control group, N = 17). Kinematics of the imitated movements were modulated by instructions, with both Imagery and Attention groups being closer in duration, peak velocity and amplitude to the observed model compared with controls. These findings show that both attention and motor imagery can increase the accuracy of imitation and have implications for motor learning and rehabilitation. Future work is required to understand the mechanisms by which these two strategies influence imitation accuracy.

The development and implementation of an interdisciplinary on-line academic course using a life course perspective.

The University of Wisconsin-Madison Pediatric Pulmonary Center (UW PPC) provides interdisciplinary leadership training for graduate students and postgraduate professionals. The training includes a three-credit on-line course entitled Interdisciplinary Care of Children with Special Health Care Needs. This paper describes the course, the content and organization of which was guided by the life course perspective (LCP). The UW PPC team used the LCP to guide course organization, content development, and evaluation approaches. UW PPC trainees took responsibility for content areas, performed literature reviews and reviews of resources, and suggested student activities. Course content was focused on the child with special health care needs (CSHCN) embedded in contextual environments of family, community, culture, and larger social and public policy arenas. The content included three case-study videos that followed a child with cystic fibrosis from birth to age 18. Key concepts of the LCP were woven in throughout the videos and other course materials. Emphasis was on representing development of the individual during critical/sensitive periods and on social determinants of health. At semester's end, qualitative and quantitative student evaluation results were very positive for all areas of the course. The final course paper, organized similarly to course modules, synthesized all aspects of the course. A successful paper included LCP concepts woven throughout to show integration of course content. The LCP provided a useful framework for course organization and content, and served as a lens through which students came to understand the care needs of CSHCN and their families. A course such as this can serve the important goal of educating future maternal child health professionals in using the LCP to understand how multiple determinants of health interact across the life span to produce health outcomes in this population.

A randomised controlled trial of additional bolus insulin using an insulin-to-protein ratio compared with insulin-to-carbohdrate ratio alone in people with type 1 diabetes following a carbohydrate-restricted diet.

AIMS: Postprandial hyperglycemia can be problematic for people with type 1 diabetes (T1DM) following carbohydrate-restricted diets. Bolus insulin calculated for meal protein plus carbohydrate may help. This study evaluated the effect of additional bolus insulin using an insulin-to-protein ratio (IPR) on glycaemic control. MATERIALS AND METHODS: Participants with T1DM aged ≥18-years were randomly allocated (1:1) to either carbohydrate and protein-based, or carbohydrate-based insulin dosing alone for 12 weeks while following a carbohydrate-restricted diet (50-100 g/day). Measurement of HbA1c and continuous glucose monitoring occurred at baseline and 12 weeks, with assessment of participant experience at 12 weeks. RESULTS: Thirty-four participants were randomised, 22 female, mean(SD): age 39.2 years (12.6) years; diabetes duration 20.6 years (12.9); HbA1c 7.3 % (0.8), 56.7 mmol/mol (9.2). Seven in each group used insulin pump therapy. HbA1c reduced at 12 weeks with no difference between treatments: mean (SD) control 7.2 % (1.0), 55.7 mmol/mol (10.6); intervention 6.9 % (0.7), 52.3 mmol/mol (7.2) (p = 0.65). Using additional protein-based insulin dosing compared with carbohydrate alone, there was no difference in glycaemic variability, time spent in euglycemic range (TIR), or below range. Participants using IPR reported more control of their diabetes, but varying levels of distress. CONCLUSIONS: Additional bolus insulin using an IPR did not improve glycaemic control or TIR in patients with well controlled T1DM following a carbohydrate-restricted diet. Importantly, the use of the IPR does not increase the risk of hypoglycemia and may be preferred.

Validation of a Quality Metric Score to Assess the Placement of Hydrogel Rectal Spacer in Patients Treated With Prostate Stereotactic Radiation Therapy.

Purpose: To evaluate the quality of the interspace between the prostate and rectum and assess the effect on the dose to the rectum by measuring the spacer quality score (SQS) before and after implanting a hydrogel rectal spacer. Methods and Materials: Thirty patients with prostate cancer were treated with stereotactic ablative body radiation therapy as part of the SPORT clinical trial. Each patient had a 10 mL polyethylene glycol hydrogel spacer inserted transperineally. Computed tomography scans were acquired before and after spacer insertion, 10MV flattening filter free (FFF) stereotactic ablative body radiation therapy (SABR) treatment plans were generated using each image set. To calculate the SQS, the prostate-rectal interspace (PRI) was measured in the anterior-posterior orientation, parallel to the anatomic midline at the prostate base, apex, and midgland on the prespacer and postspacer computed tomography. Measurements were taken in 3 transverse positions between the prostate and the rectum, and PRI scores of 0, 1, and 2 were assigned if the interspace between prostate and rectum was <0.3, 0.3 to 0.9, or ≥1 cm, respectively. The overall SQS was the lowest of the PRI scores. Differences between prespacer and postspacer PRIs and SQS were investigated by performing Fisher's exact test and differences between doses to the rectum were investigated by performing the paired samples Wilcoxon rank-sum test and Student t test. Results: Statistically significant differences between prespacer versus postspacer patients were found when grouping patients according to their overall SQS. The PRI summary score did not reach statistical significance between prespacer and postspacer at the base but was significantly higher for the prostate midline and apex. Statistically significant differences in some rectum dose-volume metrics were found when grouping patients according to their PRIs and SQS. Conclusions: SQS before and after the spacer insertion was evaluated and was found to be correlated with pre- and postspacer rectal dosimetry. Sources of improvement of the SQS scoring metric and limitations are discussed.

Evaluation of a novel phantom for the quality assurance of a six-degree-of-freedom couch 3D-printed at multiple centres.

This study aimed to validate a bespoke 3D-printed phantom for use in quality assurance (QA) of a 6 degrees-of-freedom (6DoF) treatment couch. A novel phantom design comprising a main body with internal cube structures, was fabricated at five centres using Polylactic Acid (PLA) material, with an additional phantom produced incorporating a PLA-stone hybrid material. Correctional setup shifts were determined using image registration by 3D-3D matching of high HU cube structures between obtained cone-beam computer tomography (CBCT) images to reference CTs, containing cubes with fabricated rotational offsets of 3.5°, 1.5° and -2.5° in rotation, pitch, and roll, respectively. Average rotational setup shifts were obtained for each phantom. The reproducibility of 3D-printing was probed by comparing the internal cube size as well as Hounsfield Units between each of the uniquely produced phantoms. For the five PLA phantoms, the average rot, pitch and roll correctional differences from the fabricated offsets were -0.3 ± 0.2°, -0.2 ± 0.5° and 0.2 ± 0.3° respectively, and for the PLA hybrid these differences were -0.09 ± 0.14°, 0.30 ± 0.00° and 0.03 ± 0.10°. There was found to be no statistically significant difference in average cube size between the five PLA printed phantoms, with the significant difference (P < 0.05) in HU of one phantom compared to the others attributed to setup choice and material density. This work demonstrated the capability producing a novel 3D-printed 6DoF couch QA phantom design, at multiple centres, with each unique model capable of sub-degree couch correction.

Systemic but not local rehydration restores dehydration-induced changes in pulmonary function in healthy adults.

Water transport and local (airway) hydration are critical for the normal functioning of lungs and airways. Currently, there is uncertainty regarding the effects of systemic dehydration on pulmonary function. Our aims were 1) to clarify the impact of exercise- or fluid restriction-induced dehydration on pulmonary function in healthy adults; and 2) to establish whether systemic or local rehydration can reverse dehydration-induced alterations in pulmonary function. Ten healthy participants performed four experimental trials in a randomized order (2 h exercise in the heat twice and 28 h fluid restriction twice). Pulmonary function was assessed using spirometry and whole body plethysmography in the euhydrated, dehydrated, and rehydrated states. Oral fluid consumption was used for systemic rehydration and nebulized isotonic saline inhalation for local rehydration. Both exercise and fluid restriction induced mild dehydration (2.7 ± 0.7% and 2.5 ± 0.4% body mass loss, respectively; P < 0.001) and elevated plasma osmolality (P < 0.001). Dehydration across all four trials was accompanied by a reduction in forced vital capacity (152 ± 143 mL, P < 0.01) and concomitant increases in residual volume (216 ± 177 mL, P < 0.01) and functional residual capacity (130 ± 144 mL, P < 0.01), with no statistical differences between modes of dehydration. These changes were normalized by fluid consumption but not nebulization. Our results suggest that, in healthy adults: 1) mild systemic dehydration induced by exercise or fluid restriction leads to pulmonary function impairment, primarily localized to small airways; and 2) systemic, but not local, rehydration reverses these potentially deleterious alterations.NEW & NOTEWORTHY This study demonstrates that, in healthy adults, mild systemic dehydration induced by exercise in the heat or a prolonged period of fluid restriction leads to negative alterations in pulmonary function, primarily localized to small airways. Oral rehydration, but not nebulized isotonic saline, is able to restore pulmonary function in dehydrated individuals. Our findings highlight the importance of maintaining an adequate systemic fluid balance to preserve pulmonary function.

Effect of peritoneal lavage on bacterial isolates in 40 dogs with confirmed septic peritonitis.

OBJECTIVE: To evaluate bacterial isolates, antimicrobial drug susceptibility, and change in resistance among pre- and post-lavage culture samples in dogs with septic peritonitis. DESIGN: Prospective observational study. SETTING: Private practice referral hospital. ANIMALS: Forty client-owned dogs with confirmed septic peritonitis requiring surgical intervention. INTERVENTIONS: All dogs had perioperative abdominal lavage following source control with 200 to 300 mL/kg 0.9% sterile saline. Pre- and post-lavage aerobic and anaerobic culture samples were evaluated. MEASUREMENTS AND MAIN RESULTS: Thirty-five of 40 dogs (87.5%) survived to hospital discharge. The likelihood of an aerobic organism to have multidrug resistance (resistance to 3 or more antimicrobial classes) post-lavage was a third of that pre-lavage (odds ratio [OR] 0.34, 95% CI [0.17-0.68], P = 0.01). Thirty-nine of 40 dogs (97.5%) received appropriate empiric antimicrobial therapy based on pre- and post-lavage culture results, of which 5 (12.8%) did not survive to discharge. The single dog with inappropriate antimicrobial therapy survived to discharge. The most frequent isolates detected included Escherichia coli, Clostridium perfringens, and Enterococcus faecalis. The same organism based on species was isolated in pre- and post-lavage cultures in 32 dogs, accounting for 59 anaerobic and aerobic isolates. There was a new bacterial isolate detected in 20 dogs, accounting for 46 isolates and an overall total decrease of 14 isolates between pre- and post-lavage culture (P = 0.09). CONCLUSIONS: This study suggests that there is a significant decrease in the likelihood of isolating a multidrug resistant organism following peritoneal lavage, and aerobic and anaerobic culture results have the potential to change following peritoneal lavage, although this cannot be confirmed without further studies. Overall survival rates were higher than previously reported in the literature for septic peritonitis.

Chronic probiotic supplementation with or without glutamine does not influence the eHsp72 response to a multi-day ultra-endurance exercise event.

Probiotic and glutamine supplementation increases tissue Hsp72, but their influence on extracellular Hsp72 (eHsp72) has not been investigated. The aim of this study was to investigate the effect of chronic probiotic supplementation, with or without glutamine, on eHsp72 concentration before and after an ultramarathon. Thirty-two participants were split into 3 independent groups, where they ingested probiotic capsules (PRO; n = 11), probiotic + glutamine powder (PGLn; n = 10), or no supplementation (CON; n = 11), over a 12-week period prior to commencement of the Marathon des Sables (MDS). eHsp72 concentration in the plasma was measured at baseline, 7 days pre-race, 6-8 h post-race, and 7 days post-race. The MDS increased eHsp72 concentrations by 124% (F[1,3] = 22.716, p < 0.001), but there was no difference in the response between groups. Additionally, PRO or PGLn supplementation did not modify pre- or post-MDS eHsp72 concentrations compared with CON (p > 0.05). In conclusion, the MDS caused a substantial increase in eHsp72 concentration, indicating high levels of systemic stress. However, chronic PRO or PGLn supplementation did not affect eHsp72 compared with control pre- or post-MDS. Given the role of eHsp72 in immune activation, the commercially available supplements used in this study are unlikely to influence this cascade.

An unsuccessful attempt to demonstrate attentional orienting within the purely emotional domain.

Inhibition of return (IOR) is an attentional effect that has been much researched in the spatial domain, whereby people are slower to respond to stimuli presented in a previously attended location. Recently, Chao (2010) reported that participants were slower to respond to a negative schematic facial target compared with a positive facial target if they had previously viewed a cue with a negative expression, which he interpreted as IOR in the purely emotional domain. That is, once their attention is drawn away, people are slower to reattend to negative emotions. Here, we investigated whether this effect could be observed when controlling for the valence of the target and when using a more naturalistic human facial expression as a cue. We replicated Chao's findings using real face cues, observing slower responses for negative cues followed by negative versus positive targets, and faster responses for positive cues followed by positive versus negative targets. However, our reanalysis indicates that these effects are better accounted for by the valence (positive/negative) of the target, with responses being slower to negative compared with positive facial expressions regardless of the preceding cue. In conclusion, orienting in the emotional domain could not be measured using a cue-target task, as the effect of responding to emotional targets eclipsed any potential emotional cuing effect.

The Impact of Different Environmental Conditions on Cognitive Function: A Focused Review.

Cognitive function defines performance in objective tasks that require conscious mental effort. Extreme environments, namely heat, hypoxia, and cold can all alter human cognitive function due to a variety of psychological and/or biological processes. The aims of this Focused Review were to discuss; (1) the current state of knowledge on the effects of heat, hypoxic and cold stress on cognitive function, (2) the potential mechanisms underpinning these alterations, and (3) plausible interventions that may maintain cognitive function upon exposure to each of these environmental stressors. The available evidence suggests that the effects of heat, hypoxia, and cold stress on cognitive function are both task and severity dependent. Complex tasks are particularly vulnerable to extreme heat stress, whereas both simple and complex task performance appear to be vulnerable at even at moderate altitudes. Cold stress also appears to negatively impact both simple and complex task performance, however, the research in this area is sparse in comparison to heat and hypoxia. In summary, this focused review provides updated knowledge regarding the effects of extreme environmental stressors on cognitive function and their biological underpinnings. Tyrosine supplementation may help individuals maintain cognitive function in very hot, hypoxic, and/or cold conditions. However, more research is needed to clarify these and other postulated interventions.