Barriers to paediatric penicillin allergy de-labelling in UK secondary care: a regional survey.

BACKGROUND: Incorrect penicillin allergy labels result in the use of inappropriately broad-spectrum antibiotics. De-labelling inaccurate penicillin allergy promotes antimicrobial stewardship and optimises prescribing practices. The objectives were to evaluate paediatric clinicians' knowledge and understanding of penicillin allergy and to identify barriers in tackling incorrect penicillin allergy labels. METHODS: Paediatric clinicians from across the West Midlands of the UK were surveyed using an online, anonymised questionnaire between 1 August and 30 September 2021. Domains explored were (1) approach to penicillin allergy clinical vignettes, (2) knowledge of the impact of penicillin allergy labels, (3) frequency of allergy-focused history questions and (4) barriers in tackling incorrect penicillin allergy. RESULTS: Responses were received from 307 paediatric clinicians across 12 hospitals. Sixty-one per cent would not prescribe a penicillin-based antibiotic if a family history of penicillin allergy was reported. There was an overall deficit in taking an allergy-focused history with only 36.5% inquiring about diagnostic confirmation. Absence, or lack of awareness of a referral pathway for antibiotic allergy evaluation (58.6%) and unfamiliarity of the indications for oral provocation testing (55%) were the most common reported barriers to penicillin allergy de-labelling. Fifty-one per cent would rather 'play it safe' than explore penicillin allergy confirmation as it is felt that alternative treatments were readily available. CONCLUSIONS: The deficiency in antibiotic allergy-focused history among paediatric clinicians highlights the need for better allergy education across all clinical grades. Pragmatic algorithms and clear referral pathways could address barriers faced by non-allergists in de-labelling incorrect penicillin allergy.

Inactivation strategies for SARS-CoV-2 on surgical masks using light-activated chemical dyes.

BACKGROUND: Methylene blue (MB) and riboflavin (RB) are light-activated dyes with demonstrated antimicrobial activity. They require no specialized equipment, making them attractive for widespread use. Due to COVID-19-related worldwide shortages of surgical masks, simple, safe, and effective decontamination methods for reusing masks have become desirable in clinical and public settings. MATERIAL AND METHODS: We examined the decontamination of SARS-CoV-2 Beta variant on surgical masks and Revolution-Zero Environmentally Sustainable (RZES) reusable masks using these photoactivated dyes. We pre-treated surgical masks with 2 MB concentrations, 2 RB concentrations, and 2 combinations of MB and RB. We also tested 7 MB concentrations on RZES masks. RESULTS: Photoactivated MB consistently inactivated SARS-CoV-2 at >99.9% for concentrations of 2.6 µM or higher within 30 min on RZES masks and 5 µM or higher within 5 min on disposable surgical masks. RB alone showed a lower, yet still significant inactivation (∼93-99%) in these conditions. DISCUSSION: MB represents a cost-effective, rapid, and widely deployable decontamination method for SARS-CoV-2. The simplicity of MB formulation makes it ideal for mask pre-treatment in low-resource settings. CONCLUSIONS: The results demonstrate that MB effectively decontaminates SARS-CoV-2 at concentrations above 5 µM on surgical masks and above 10 µM on RZES masks.

Preventive Digital Mental Health for Children in Primary Schools: Acceptability and Feasibility Study.

BACKGROUND: The incidence of mental health problems in children and adolescents in the United Kingdom has significantly increased in recent years, and more people are in contact with mental health services in Greater Manchester than in other parts of the country. Children and young people spend most of their time at school and with teachers. Therefore, schools and other educational settings may be ideal environments in which to identify those experiencing or those at the risk of developing psychological symptoms and provide timely support for children most at risk of mental health or related problems. OBJECTIVE: This study aims to test the feasibility of embedding a low-cost, scalable, and innovative digital mental health intervention in schools in the Greater Manchester area. METHODS: Two components of a 6-week digital intervention were implemented in a primary school in Greater Manchester: Lexplore, a reading assessment using eye-tracking technology to assess reading ability and detect early atypicality, and Lincus, a digital support and well-being monitoring platform. RESULTS: Of the 115 children approached, 34 (29.6%) consented and took part; of these 34 children, all 34 (100%) completed the baseline Lexplore assessment, and 30 (88%) completed the follow-up. In addition, most children were classified by Lincus as regular (≥1 per week) survey users. Overall, the teaching staff and children found both components of the digital intervention engaging, usable, feasible, and acceptable. Despite the widespread enthusiasm and recognition of the potential added value from staff, we met significant implementation barriers. CONCLUSIONS: This study explored the acceptability and feasibility of a digital mental health intervention for schoolchildren. Further work is needed to evaluate the effectiveness of the digital intervention and to understand whether the assessment of reading atypicality using Lexplore can identify those who require additional help and whether they can also be supported by Lincus. This study provides high-quality pilot data and highlights the potential benefits of implementing digital assessment and mental health support tools in a primary school setting.

Coastal heritage, global climate change, public engagement, and citizen science.

Climate change is threatening an uncalculated number of archaeological sites globally, totaling perhaps hundreds of thousands of culturally and paleoenvironmentally significant resources. As with all archaeological sites, they provide evidence of humanity's past and help us understand our place in the present world. Coastal sites, clustered at the water's edge, are already experiencing some of the most dramatic damage due to anthropogenic climate change, and the situation is predicted to worsen in the future. In the face of catastrophic loss, organizations around the world are developing new ways of working with this threatened coastal resource. This paper uses three examples from Scotland, Florida, and Maine to highlight how new partnerships and citizen science approaches are building communities of practice to better manage threatened coastal heritage. It compares methods on either side of the Atlantic and highlights challenges and solutions. The approaches are applicable to the increasing number of heritage sites everywhere at risk from climate change; the study of coastal sites thus helps society prepare for climate change impacts to heritage worldwide.

Skin Fungi from Colonization to Infection.

Humans are exceptional among vertebrates in that their living tissue is directly exposed to the outside world. In the absence of protective scales, feathers, or fur, the skin has to be highly effective in defending the organism against the gamut of opportunistic fungi surrounding us. Most (sub)cutaneous infections enter the body by implantation through the skin barrier. On intact skin, two types of fungal expansion are noted: (A) colonization by commensals, i.e., growth enabled by conditions prevailing on the skin surface without degradation of tissue, and (B) infection by superficial pathogens that assimilate epidermal keratin and interact with the cellular immune system. In a response-damage framework, all fungi are potentially able to cause disease, as a balance between their natural predilection and the immune status of the host. For this reason, we will not attribute a fixed ecological term to each species, but rather describe them as growing in a commensal state (A) or in a pathogenic state (B).

UK Health and Social Care Case Studies: Iterative Technology Development.

As a result of increasing demand in the face of reducing resources, technology has been implemented in many social and health care services to improve service efficiency. This paper outlines the experiences of deploying a 'Software as a Service' application in the UK social and health care sectors. The case studies demonstrate that every implementation is different, and unique to each organisation. Technology design and integration can be facilitated by ongoing engagement and collaboration with all stakeholders, flexible design, and attention to interoperability to suit services and their workflows.

Evaluation of AllergiSense Smartphone Tools for Adrenaline Injection Training.

Anaphylaxis is an increasingly prevalent life-threatening allergic condition that requires people with anaphylaxis and their caregivers to be trained in the avoidance of allergen triggers and in the administration of adrenaline autoinjectors. The prompt and correct administration of autoinjectors in the event of an anaphylactic reaction is a significant challenge in the management of anaphylaxis. Unfortunately, many people do not know how to use autoinjectors and either fail to use them or fail to use them correctly. This is due in part to deficiencies in training and also to the lack of a system encouraging continuous practice with feedback. Assistive smartphone healthcare technologies have demonstrated potential to support the management of chronic conditions such as diabetes and cardiovascular disease, but there have been deficiencies in their evaluation and there has been a lack of application to anaphylaxis. This paper describes AllergiSense, a smartphone app and sensing system for anaphylaxis management, and presents the results of a randomized, controlled, prepost evaluation of AllergiSense injection training and feedback tools with healthy participants. Participants whose training was supplemented with AllergiSense injection feedback achieved significantly better practiced injections with 90.5% performing correct injections compared to only 28.6% in the paper-only control group. In addition, the results provide insights into possible self-efficacy failings in traditional training and the benefits of embedding self-efficacy theory into the technology design process.

Hair care practices and structural evaluation of scalp and hair shaft parameters in African American and Caucasian women.

How African American hair fragility relates to hair care practices and biologic differences between races is not well understood. To assess the differences between perceptions of hair health, hair care practices, and several biologic hair parameters between Caucasian and African American women. A questionnaire on perceptions of hair health and hair care practices was administered. Biological and structural parameters of hair shaft and scalp, including growth, density, diameter, cycle, breakage, and scalp blood flow were also assessed in this case-control study. Significant differences between the Caucasian and African American women were observed in the questionnaire and biologic study data. Regarding self-reported perceptions of hair health, there were differences in the following: hair shaft type (P < 0.001), hair breakage (P = 0.040), and desire to change hair (P = 0.001). Regarding self-reported hair care practices, there were differences in the following: location of haircutting (P = 0.002) and washing (P = 0.010), washing frequency (P < 0.001), chemical relaxer use (P < 0.001), hooded hair dryer use (P < 0.001), and hair shaft conditioner use (P = 0.005). The two groups had similar practices in regard to the use of hair color, frequency of hair color use, chemical curling agents, and handheld blow dryer use. Regarding biological and structural parameters, there were differences in the following: hair growth rate (P < 0.001), density (P = 0.0016), diameter (P = 0.01), number of broken hairs (P < 0.001), and blood flow (P = 0.03). There was no significant difference in hair cycle parameters.The differences in hair care practices and hair fiber morphology among African American women may contribute to clinically observed variation in hair fragility and growth.

A view from Scotland's coast.

Coastal erosion is one of the gravest natural threats to our shared heritage. Although climate change predictions suggest that things will worsen in the future, the problem is already with us. In Scotland, the SCAPE (Scottish Coastal Archaeology and the Problem of Erosion) Trust and the University of St Andrews have been working with the public for many years. Their latest project, SCHARP, works with the public to update previous surveys and to nominate and undertake practical projects at locally valued sites. The project is increasing public knowledge about how climatic events are altering coastlines and informing management decisions, while providing the public a stake in their coastal heritage.

No association between ACE gene variation and endurance athlete status in Ethiopians.

PURPOSE: The most widely studied candidate gene for endurance performance is the angiotensin-converting enzyme (ACE) gene. The best endurance runners in the world hail from Kenya and Ethiopia, so the lack of association between the ACE gene and elite endurance athlete status we previously reported in Kenyans requires replication in Ethiopians. METHODS: DNA was extracted from buccal swabs collected from subjects filling four groups: elite endurance runners from the Ethiopian national athletics team specializing in 5 km to marathon distances (n = 76), controls demographically matched to the elite endurance athletes (n = 410), controls representing the general Ethiopian population (n = 317), and sprint and power event athletes from the Ethiopian national athletics team (n = 38). ACE I/D and A22982G (rs4363) genotype frequencies were determined for each of these groups, and differences between groups were assessed using χ(2) tests. RESULTS: There were no significant deviations from Hardy-Weinberg equilibrium in endurance athletes or either control group. Endurance athletes did not differ significantly in ACE I/D genotype frequency when compared with the endurance athlete-matched control group (P = 0.16), general controls (P = 0.076), or sprint and power athletes (P = 0.39) (endurance athletes: 15.8% II, endurance athlete-matched controls: 8.8% II, general controls: 7.6% II, sprint and power athletes: 10.5% II). Similarly, no significant differences were found in ACE A22982G genotype between groups (endurance athletes: 13.2% AA, endurance athlete-matched controls: 12.2% AA, general controls: 12.0% AA, sprint and power athletes: 13.2%; endurance athletes vs endurance athlete-matched controls: P = 0.97, endurance athletes vs general controls: P = 0.95, endurance athletes vs sprint and power athletes: P = 0.52). CONCLUSIONS: As previously shown in elite Kenyan athletes, ACE I/D and A22982G polymorphisms are not associated with elite endurance athlete status in Ethiopians.

Multicenter, open-label, randomized phase II controlled trial of an investigational recombinant Meningococcal serogroup B vaccine with and without outer membrane vesicles, administered in infancy.

BACKGROUND: In the absence of an efficacious broadly protective vaccine, serogroup B Neisseria meningitidis (MenB) is the leading cause of bacterial meningitis and septicemia in many industrialized countries. An investigational recombinant vaccine that contains 3 central proteins; Neisserial adhesin A (NadA), factor H binding protein (fHBP) and Neisserial heparin binding antigen (NHBA) has been developed. These antigens have been formulated with and without outer membrane vesicles (rMenB+OMV and rMenB, respectively) from the New Zealand epidemic strain (B:4:P1.7-2,4). In this trial, we assessed the immunogenicity of these formulations in infants, who are at greatest risk of contracting MenB disease. METHODS: A total of 147 infants from the United Kingdom were enrolled and randomly assigned to receive rMenB or rMenB+OMV at 2, 4, 6, and 12 months of age or a single dose at 12 months of age. Serum samples taken before and after vaccination were assayed in a standardized serum bactericidal antibody assay against 7 MenB strains. Local and systemic reactogenicity were recorded for 7 days after each vaccination. Analysis was according to protocol. RESULTS: After 3 doses, both vaccines were immunogenic against strains expressing homologous or related NadA and fHBP. rMenB+OMV demonstrated greater immunogenicity than did rMenB and was immunogenic against strains expressing homologous PorA. Both vaccines elicited anamnestic responses after the fourth dose. For both vaccines, responses were lower against strains expressing heterologous fHBP variants and after a single dose at 12 months. CONCLUSIONS: The rMenB+OMV vaccine has the potential to protect infants from MenB disease, although the breadth of protection afforded to heterologous antigens requires additional investigation.

Immunogenicity of two investigational serogroup B meningococcal vaccines in the first year of life: a randomized comparative trial.

BACKGROUND: An investigational vaccine against serogroup B meningococcal (MenB) disease containing 3 main recombinant proteins (factor H-binding protein, Neisserial adhesion A, and Neisserial heparin-binding antigen) has been developed. We evaluated the immunogenicity and reactogenicity of a 3-dose course of this vaccine administered alone (recombinant MenB [rMenB]) or combined with the outer membrane vesicle (OMV) component of the vaccine used in New Zealand (rMenB+OMV). METHODS: A randomized, single-blind, comparative study of 60 healthy infants enrolled at 6 to 8 months of age and immunized with rMenB or rMenB+OMV at day 0, day 60, and at age 12 months. Blood samples obtained at baseline and 1 month following the second and third doses of vaccine were analyzed for serum bactericidal antibody (SBA) using human complement (hSBA) against 7 MenB strains. The putative correlate of protection was an hSBA titer of ≥4. RESULTS: The per-protocol analysis included 24 of 30 participants randomized to each group. After 3 doses of rMenB+OMV, 90% or more of participants had an hSBA titer ≥4 for 5 MenB strains, with 70% of participants having an hSBA titer ≥4 for a sixth strain. rMenB alone was immunogenic for only 3 strains. Both vaccines were well tolerated. CONCLUSIONS: Three doses of rMenB+OMV in the second half of infancy induce bactericidal antibodies against strains expressing vaccine antigens, demonstrating the potential for broader vaccine prevention of MenB disease. This vaccine is now in phase III clinical trials.

Optimizing exercise outcomes: the efficacy of resistance training using conventional vs. novel movement arcs.

The purpose of this study was to examine the effect of using multidirectional movement arcs in a resistance training program for the shoulder. It was hypothesized that multidirectional exercises performed against resistance would result in a greater positive adaptation of the muscle tissue than conventional movement patterns commonly used in strength training. Fourteen female athletes were initially assessed using a 1x repetition maximum (1xRM) test for shoulder flexion and shoulder abduction (dominant and nondominant arm). After randomization into 2 groups, subjects engaged in different strength training programs against Thera-Band resistance for 6 weeks. Follow-up testing was then completed. Group A was assigned a strength training program that used conventional curvilinear movement arcs. Group B completed resistance training that comprised multidirectional exercises. Both the conventional and novel strength training programs induced improvements in the 1x RM test (p < 0.01). There was a trend toward greater improvements in the nonconventional training group, but this was statistically insignificant. This suggests that varying the axial or torsional loading of muscle fibers during strength training may confer further benefit to conventional methods of training variation. Consequently, further studies are indicated to investigate if resistance training that incorporates multidirectional movement arcs is more effective than those used in conventional strength training programs. This may have implications on the design of future training programs that aim to optimize strength gains.

Long-term effect of neuronal nitric oxide synthase over-expression on cardiac neurotransmission mediated by a lentiviral vector.

Short-term over-expression of neuronal nitric oxide synthase (nNOS) with adenoviral gene transfer into peripheral cardiac autonomic neurons can facilitate cholinergic neurotransmission, and inhibit sympathetic transmission, by regulating cyclic nucleotide-dependent pathways coupled to neuronal calcium entry. We tested the idea whether cardiac neuromodulation by nNOS could be sustained by long-term over-expression of the enzyme following lentiviral gene transfer. We developed a lentiviral vector with an elongation factor 1 (EF1alpha) promoter to drive nNOS or enhanced green fluorescent protein (eGFP) expression. Lenti.EF1alpha-nNOS or Lenti.EF1alpha-eGFP was transferred to the right atrium of Spague-Dawley (SD) rats and acetylcholine (ACh) or noradrenaline (NA) release to field stimulation was measured 4 months after gene transfer. Atria transduced with Lenti.EF1alpha-nNOS had higher nNOS expression compared to the atria treated with Lenti.EF1alpha-eGFP (P < 0.05). We also detected significant increases (P < 0.05) in atrial cGMP and cAMP levels in the same tissue. Immunohistochemistry revealed co-localisation of eGFP in intrinsic cholinergic neurons (choline acetyltransferase positive) and intrinsic adrenergic neurons (tyrosine hydroxylase positive) following gene transfer. nNOS-transduced animals displayed enhanced ACh release (P < 0.05) and reduced NA release (P < 0.05) compared to the eGFP-treated group. nNOS-specific inhibition reversed the enhanced ACh release. Persistent nNOS over-expression mediated by a lentiviral vector can modulate sympatho-vagal control of cardiac excitability. This approach may provide a new tool to target impaired cardiac autonomic phenotypes that are disrupted by several cardiovascular pathologies.

Effects of acute vagal nerve stimulation on the early passive electrical changes induced by myocardial ischaemia in dogs: heart rate-mediated attenuation.

Parasympathetic activity during acute coronary artery occlusion (CAO) can protect against ischaemia-induced malignant arrhythmias; nonetheless, the mechanism mediating this protection remains unclear. During CAO, myocardial electrotonic uncoupling is associated with autonomically mediated immediate (i.e. type 1A) arrhythmias and can modulate pro-arrhythmic dispersion of repolarization. Therefore, the effects of acutely enhanced or decreased cardiac parasympathetic activity on early electrotonic coupling during CAO, as measured by myocardial electrical impedance (MEI), were investigated. Anaesthetized dogs were instrumented for MEI measurements, and left circumflex coronary arterial occlusions were performed in intact (CTRL) and vagotomized (VAG) animals. The CAO was followed by either vagotomy (CTRL) or vagal nerve stimulation (VNS, 10 Hz, 10 V) in the VAG dogs. Vagal nerve stimulation was studied in two additional sets of animals. In one set heart rate (HR) was maintained by pacing (220 beats min(-1)), while in the other set bilateral stellectomy preceded CAO. The MEI increased after CAO in all animals. A larger MEI increase was observed in vagotomized animals (+85 +/- 9 Omega, from 611 +/- 24 Omega, n = 16) when compared with intact control dogs (+43 +/- 5 Omega, from 620 +/- 20 Omega, n = 7). Acute vagotomy during ischaemia abruptly increased HR (from 155 +/- 11 to 193 +/- 15 beats min(-1)) and MEI (+12 +/- 1.1 Omega, from 663 +/- 18 Omega). In contrast, VNS during ischaemia (n = 11) abruptly reduced HR (from 206 +/- 6 to 73 +/- 9 beats min(-1)) and MEI (-16 +/- 2 Omega, from 700 +/- 44 Omega). These effects of VNS were eliminated by pacing but not by bilateral stellectomy. Vagal nerve stimulation during CAO also attenuated ECG-derived indices of ischaemia (e.g. ST segment, 0.22 +/- 0.03 versus 0.15 +/- 0.03 mV) and of rate-corrected repolarization dispersion [terminal portion of T wave (TPEc), 84.5 +/- 4.2 versus 65.8 +/- 5.9 ms; QTc, 340 +/- 8 versus 254 +/- 16 ms]. Vagal nerve stimulation during myocardial ischaemia exerts negative chronotropic effects, limiting early ischaemic electrotonic uncoupling and dispersion of repolarization, possibly via a decreased myocardial metabolic demand.

Noradrenergic cell specific gene transfer with neuronal nitric oxide synthase reduces cardiac sympathetic neurotransmission in hypertensive rats.

Nitric oxide-cGMP pathway can inhibit cardiac norepinephrine (NE) release. Sympathetic hyper-responsiveness in hypertension may result from oxidative stress impairing this pathway. We tested the hypothesis that the gene transfer of neuronal NO synthase (nNOS) could restore sympathetic balance in the spontaneously hypertensive rat (SHR). An adenovirus (5x10(10) particles) constructed with a noradrenergic neuron-specific promoter (PRS x8) encoding nNOS (Ad.PRS-nNOS) or enhanced green fluorescence protein (Ad.PRS-eGFP) was targeted to the right atrial wall by percutaneous injection in age-matched male SHRs and Wistar-Kyoto (WKY) rats. Five days after transduction, right atria were removed, and evoked [(3)H] norephinephrine (NE) release, NOS activity, and cGMP were measured. In the Ad.PRS-eGFP treated group, tissue levels of cGMP were significantly lower in the SHR compared with the WKY atria. NE release was also greater in the SHR, and soluble guanylate cyclase inhibition did not alter evoked [(3)H] NE release in the Ad.PRS-eGFP-treated SHR. All atria treated with Ad.PRS-nNOS had enhanced nNOS activity when compared with Ad.PRS-eGFP atria. Ad.PRS-nNOS in WKY rats reduced NE release compared with the Ad.PRS-eGFP group. Guanylate cyclase inhibition enhanced NE release in both Ad.PRS-nNOS- and Ad.PRS-eGFP-treated WKY atria. Ad.PRS-nNOS restored cGMP levels in the SHR to those seen in the WKY atria. In the SHR, Ad.PRS-nNOS also attenuated NE release compared with Ad.PRS-eGFP group. This was reversed by guanylate cyclase inhibition. We conclude that artificial upregulation of sympathetic nNOS via gene transfer with a noradrenergic promoter may provide a novel approach for correcting peripheral sympathetic hyperactivity in hypertension.

Gene transfer of neuronal nitric oxide synthase into intracardiac Ganglia reverses vagal impairment in hypertensive rats.

Hypertension is associated with reduced cardiac vagal activity and decreased atrial guanylate cyclase and cGMP levels. Neuronal production of NO facilitates cardiac parasympathetic transmission, although oxidative stress caused by hypertension may disrupt this pathway. We tested the hypothesis that peripheral vagal responsiveness is attenuated in the spontaneously hypertensive rat (SHR) because of impaired NO-cGMP signaling and that gene transfer of neuronal NO synthase (nNOS) into cholinergic intracardiac ganglia can restore neural function. Cardiac vagal heart rate responses in the isolated SHR atrial/right vagus preparation were significantly attenuated compared with age-matched normotensive Wistar-Kyoto rats. [(3)H] acetylcholine release was also significantly lower in the SHR. The NO donor, sodium nitroprusside, augmented vagal responses to nerve stimulation and [(3)H] acetylcholine release in the Wistar-Kyoto rat, whereas the soluble guanylate cyclase inhibitor 1H-(1,2,4)oxadiazolo(4,3-a)quinoxaline-1-one attenuated [(3)H] acetylcholine release in Wistar-Kyoto atria. No effects of sodium nitroprusside or 1H-(1,2,4)oxadiazolo(4,3-a)quinoxaline-1-one were seen in the SHR during nerve stimulation. In contrast, SHR atria were hyperresponsive to carbachol-induced bradycardia, with elevated production of atrial cGMP. After gene transfer of adenoviral nNOS into the right atrium, vagal responsiveness in vivo was significantly increased in the SHR compared with transfection with adenoviral enhanced green fluorescent protein. Atrial nNOS activity was increased after gene transfer of adenoviral nNOS, as was expression of alpha(1)-soluble guanylate cyclase in both groups compared with adenoviral enhanced green fluorescent protein. In conclusion, a significant component of cardiac vagal dysfunction in hypertension is attributed to an impairment of the postganglionic presynaptic NO-cGMP pathway and that overexpression of nNOS can reverse this neural phenotype.