Multidimensional analysis for the correlation of physico-chemical attributes to osteoblastogenesis in TiNbZrSnTa alloys.

Data-enabled approaches that complement experimental testing offer new capabilities to investigate the interplay between chemical, physical and mechanical attributes of alloys and elucidate their effect on biological behaviours. Reported here, instead of physical causation, statistical correlations were used to study the factors responsible for the adhesion, proliferation and maturation of pre-osteoblasts MC3T3-E1 cultured on Titanium alloys. Eight alloys with varying wt% of Niobium, Zirconium, Tin and Tantalum (Ti- (2-22 wt%)Nb- (5-20 wt%)Zr- (0-18 wt%)Sn- (0-14 wt%)Ta) were designed to achieve exemplars of allotropes (incl., metastable-ß, ß + α', α″). Following confirmation of their compositions (ICP, EDX) and their crystal structure (XRD, SEM), their compressive bulk properties were measured and their surface features characterised (XPS, SFE). Because these alloys are intended for the manufacture of implantable orthopaedic devices, the correlation focuses on the effect of surface properties on cellular behaviour. Physico-chemical attributes were paired to biological performance, and these highlight the positive interdependencies between oxide composition and proliferation (esp. Ti4+), and maturation (esp. Zr4+). The correlation reveals the negative effect of oxide thickness, esp. TiOx and TaOx on osteoblastogenesis. This study also shows that the characterisation of the chemical state and elemental electronic structure of the alloys' surface is more predictive than physical properties, namely SFE and roughness.

Towards a regulation of food advertising?

For 20 years the UK Government has recognised that food advertising plays a part in food choices and hence diets of the population, particularly for children. In 2007 the UK brought in regulations to stop the advertising of less healthy foods on television (TV) during child-specific programming. Less healthy foods were defined using the 2004/2005 nutrient profiling model (NPM) as products high in saturated fat, salt and sugar (HFSS). Evaluations showed that children were still seeing and being affected by the adverts for less healthy foods. To try to mitigate childhood obesity, in 2018, the UK Government announced its intention to consult on further restrictions on the advertising of HFSS products on TV and online. Two years later, the intention to implement a 9pm advertising ban on TV and a further consultation on restricting online advertising of HFSS products was announced. New legislative controls on the advertising of HFSS foods are expected to be brought into legislation in the UK in January 2024. In the present paper, the history of advertising restrictions in the UK and the evidence informing them is reviewed. There will also be a reflection on where further actions might be needed in due course.

Vulvar Fordyce adenitis: A cohort of 45 women.

BACKGROUND: Recurrent episodes of painful papules and nodules, mostly located on the labia minora, have been reported under the denominations of vulvar sebaceous adenitis (14 published cases) and vulvar acne (16 published cases). OBJECTIVES: The primary aim of this study was to delve further into the clinical and pathological features of this condition. The secondary aim was to collect therapeutic data. METHODS: In this retrospective cohort study, files and photographs of patients with papules or nodules on the labia minora or the inner labia majora were extracted from a vulvar clinic database. Clinical, pathological and therapeutic data were analysed. RESULTS: Forty-five women were included from 2002 to 2018. The median age at the time of diagnosis was 36 years (range: 16-60). The median time to diagnosis was 6.5 years. Clinical features included recurrent painful papules, pustules or nodules, suppuration (n=22), and pitted scars (n=10) on the labia minora (n=41), the inner labia majora (n=19), the outer labia majora (n=1), and the clitoral hood (n=1). Associated acne vulgaris was seen in 17 out of 26 patients for whom data were available. Hidradenitis suppurativa, androgenic alopecia and hirsutism were observed in 3, 1 and 1 cases respectively. Neutrophilic infiltrates were observed in the 4 available biopsies within or around the Fordyce sebaceous glands in 2 patients. Treatment with tetracyclines and oral zinc was not consistently effective. Isotretinoin led to complete remission in 4 patients unresponsive to tetracyclines. DISCUSSION: Vulvar sebaceous adenitis/vulvar acne is a clinically identifiable cause of painful recurrent inflammatory lesions affecting the labia minora and the inner labia majora, which are coincidentally sites of Fordyce granules. We therefore suggest a more specific denomination: "vulvar Fordyce adenitis". The relationship with acne vulgaris and hidradenitis suppurativa requires further investigation. We suggest use of an oral anti-acne therapeutic strategy to reduce inflammation and to decrease the secretion of the sebaceous glands.

Stop-signal reaction time correlates with a compensatory balance response.

BACKGROUND: Response inhibition involves suppressing automatic, but unwanted action, which allows for behavioral flexibility. This capacity could theoretically contribute to fall prevention, especially in the cluttered environments we face daily. Although much has been learned from cognitive psychology regarding response inhibition, it is unclear if such findings translate to the intensified challenge of coordinating balance recovery reactions. RESEARCH QUESTION: Is the ability to stop a prepotent response preserved when comparing performance on a standard test of response inhibition versus a reactive balance test where compensatory steps must be occasionally suppressed? METHODS: Twelve young adults completed a stop signal task and reactive balance test separately. The stop signal task evaluates an individual's ability to quickly suppress a visually-cued button press upon hearing a 'stop' tone, and provides a measure of the speed of response inhibition called the Stop Signal Reaction Time (SSRT). Reactive balance was tested by releasing participants from a supported lean position, in situations where the environment was changed during visual occlusion. Upon receiving vision, participants were required to either step to regain balance following cable release (70% of trials), or suppress a step if an obstacle was present (30% of trials). The early muscle response of the stepping leg was compared between the 'step blocked' and 'step allowed' trials to quantify step suppression. RESULTS: SSRT was correlated with muscle activation of the stepping leg when sufficient time was provided to view the response environment (400 ms). Individuals with faster SSRTs exhibited comparably less leg muscle activity when a step was blocked, signifying a superior ability to inhibit an unwanted step. SIGNIFICANCE: Performance on a standardized test of response inhibition is related to performance on a reactive balance test where automated stepping responses must occasionally be inhibited. This highlights a generalizable neural mechanism for stopping action across different behavioral contexts.

A quality improvement project to increase self-administration of medicines in an acute hospital.

QUALITY PROBLEM OR ISSUE: A patient survey found significantly fewer patients reported they had self-administered their medicines while in hospital (20% of 100 patients) than reported that they would like to (44% of 100). We aimed to make self-administration more easily available to patients who wanted it. INITIAL ASSESSMENT: We conducted a failure, modes and effects analysis, collected baseline data on four wards and carried out observations. CHOICE OF SOLUTION: Our initial assessment suggested that the main areas we should focus on were raising patient awareness of self-administration, changing the patient assessment process and creating a storage solution for medicines being self-administered. We developed new patient information leaflets and posters and a doctor's assessment form using Plan-Do-Study-Act cycles. We developed initial designs for a storage solution. IMPLEMENTATION: We piloted the new materials on three wards; the fourth withdrew due to staff shortages. EVALUATION: Following collection of baseline data, we continued to collect weekly data. We found that the proportion of patients who wished to self-administer who reported that they were able to do so, significantly increased from 41% (of 155 patients) to 66% (of 118 patients) during the study, despite a period when the hospital was over capacity. LESSONS LEARNED: Raising and maintaining healthcare professionals' awareness of self-administration can greatly increase the proportion of patients who wish to self-administer who actually do so. Healthcare professionals prefer multi-disciplinary input into the assessment process.

Nurses' and pharmacists' learning experiences from participating in interprofessional medication reviews for elderly in primary health care - a qualitative study.

BACKGROUND: Traditionally, drug prescription and follow up have been the sole responsibility of physicians. However, interprofessional medication reviews (IMRs) have been developed to prevent drug discrepancies and patient harm especially for elderly patients with polypharmacy and multimorbidity. What participating nurses and pharmacists learn from each other during IMR is poorly studied. The aim of this study was to investigate nurses' and pharmacists' perceived learning experience after participating in IMRs in primary health care for up to two years. METHODS: A qualitative study with semi-structured focus group interviews and telephone interviews with nurses and pharmacists with experience from IMRs in nursing homes and home based services. The data was analysed thematically by using systematic text condensation. RESULTS: Thirteen nurses and four pharmacists were interviewed. They described some challenges concerning how to ensure participation of all three professions and how to get thorough information about the patient. As expected, both professions talked of an increased awareness with time of the benefit of working as a team and the perception of contributing to better and more individual care. The nurses' perception of the pharmacist changed from being a controller of drug management routines towards being a source of pharmacotherapy knowledge and a discussant partner of appropriate drug therapy in the elderly. The pharmacists became more aware of the nurses' crucial role of providing clinical information about the patient to enable individual advice. Increasingly the nurses learned to link the patient's symptoms of effect and side effect to the drugs prescribed. CONCLUSIONS: Although experiencing challenges in conducting IMRs, the nurses and pharmacists had learning experiences they said improved both their own practice and the quality of drug management. There are some challenges concerning how to ensure participation of all three professions and how to get thorough information about the patient.

Respiratory autoresuscitation following severe acute hypoxemia in anesthetized adult rats.

In the present study we investigated the pattern and efficacy of respiratory autoresuscitation in spontaneously breathing adult male rats across three separate anesthetic backgrounds. Each animal was administered one of three injectable anesthetics to achieve a surgical plane of anesthesia: ketamine-xylazine (KET, n=10), pentobarbital (PEN, n=10), or urethane (URE, n=10). Animals were tracheostomized and equipped with a femoral artery catheter to record airflow and arterial pressures. In response to a bout of breathing anoxic air, none of the 10 URE animals were able to mount a successful autoresuscitation response. In contrast, all KET and PEN animals survived all four consecutive anoxic exposures, restoring eupneic breathing in all cases. Moreover, only 4/10 URE animals expressed gasping breaths following the onset of respiratory arrest, and these were temporally delayed (p<0.001) and much smaller in volume (P≤0.012) compared to KET and PEN animals. URE animals showed no clear aberrations in their cardiovascular responses to anoxia, with the exception of lower arterial pulse pressures compared to either KET or PEN animals at specific points following RA. Ketamine-xylazine and pentobarbital anesthesia can be reliably and effectively used to create models for the study of autoresuscitation in adult rats. In contrast, urethane causes catastrophic failure of respiratory autoresuscitation, by delaying or outright preventing the elaboration of gasping breaths following anoxia-induced respiratory arrest. The neuronal and synaptic alterations accompanying urethane anesthesia may therefore provide a means of understanding potential pathological alterations in rhythm generation that can predispose the respiratory control system to failed autoresuscitation following an episode of acute severe hypoxemia.

A multi-centre audit on genital lichen sclerosus in the North West of England.

BACKGROUND: Guidelines for the management of genital Lichen sclerosus (LS) have recently been updated. OBJECTIVE: To look at the audit points suggested by the updated guidelines: performance of biopsies in active LS not responding to treatment; clear follow-up arrangements for patients with active disease; patient awareness of need to report suspicious lesions; and use of an appropriate topical steroid regieme. METHOD: Patients with a diagnosis of genital LS seen over the preceding 12 months were identified from eight hospital Trusts. In this study, 194 patients participated, 178 females and 16 males. RESULTS: The diagnosis was purely clinical in 62 patients - the remainder required biopsies. The commonest reason for performing a biopsy was to clarify the diagnosis (116), followed by to rule out malignancy (11). The majority (98%) were offered follow-up after the initial consultation and only 19 patients were discharged to primary care. In this study, 37% patients had documented evidence that a patient information leaflet had been given. 112 were treated with the clobetasol propionate 0.05% regieme quoted in the guideline. CONCLUSION: We conclude biopsies should be done as indicated in the guideline and the reason for biopsy documented. Discharge may be possible at 6 months for stable uncomplicated disease, although this may prove difficult if adequate follow-up arrangements are not available in the community. We advocate that all patients should receive a patient information leaflet and must be made aware of the increased risk of SCC. Topical corticosteroid treatment should be simplied to the regieme documented in the guidelines unless contraindicated.

Real-life experience of managing vulval erosive lichen planus: a case-based review and U.K. multicentre case note audit.

BACKGROUND: There is a lack of published evidence for treatment and outcome measures for vulval erosive lichen planus (ELPV). OBJECTIVES: To conduct a multicentre case note review to examine real-life management of ELPV comparing current U.K. practice against an agreed audit standard. METHODS: Criteria for standards of care for which to evaluate current service provision were set following communication with experts from the British Society for the Study of Vulval Disease. Participants from 10 U.K. centres included nine dermatologists and one gynaecologist who run specialist vulval clinics. Standards examined the documentation of disease severity/impact measures, the use of diagnostic biopsies, treatments used and assessment of treatment response. RESULTS: Audit data were collected from 172 patients. Documentation of symptoms/clinical findings was excellent (99%, 170/172). A schematic diagram was present in the notes of 87% (150/172). Patient-related disease impact measures including Dermatology Life Quality Index (3%, 6/172) or visual analogue scales (1%, 2/172) were less well documented. Biopsies were performed in 78% (135/172); 71% (96/135) showed histological features consistent with erosive lichen planus. Squamous cell carcinoma developed in four patients (two vulval, two oral) and vulval intraepithelial neoplasia in two further patients. Recommended first-line treatment with a very potent topical steroid was used in 75% (129/172) with improvement in 66% (85/129). Significant variation in second-line therapy was seen. CONCLUSIONS: Wide variation in U.K. practice demonstrates the absence of standardized guidance for treating ELPV and the need for vulval-specific outcomes. This audit should act as a framework towards improving ELPV management and to plan future research in this area.

Hypocapnia-dependent facilitation of augmented breaths: observations in awake vs. anesthetized rats.

We investigated whether commonly used injectable laboratory anesthetics alter the regulation of augmented breaths (ABs) in different respiratory backgrounds. Male rats were studied on three separate experimental days, receiving one of three injections in randomized order: ethyl carbamate ('urethane'; 1.2mgkg(-1)), ketamine/xylazine (ket/xyl; 80/10mgkg(-1)), or normal saline. Following each of the three interventions, breathing was monitored during 15min exposures to normoxia (room air), hypoxia (10% O(2)) and hypoxia+CO(2) (10% O(2), 5% CO(2)). Urethane anesthesia completely eliminated ABs from the breathing rhythm in room air conditions (p<0.001), and decreased the hypocapnia-dependent component of this response (p<0.001). ket/xyl left the normal incidence of ABs in room air breathing intact but significantly suppressed the hypoxia-induced facilitation of ABs (p=0.0015). These results provide the first clear evidence that laboratory anesthesia can profoundly alter the regulation of ABs including the hypocapnia-dependent component of their facilitation.

Recombinant conotoxin, TxVIA, produced in yeast has insecticidal activity.

Conotoxins are a diverse collection of more than 50,000 peptides produced by predatory marine snails of the genus Conus in order to immobilize their prey. Many conotoxins modulate the activity of ion channels, and show high specificity to their targets; as a result, some have valuable pharmaceutical applications. However, obtaining active peptide is difficult and to date has only been achieved though natural collection, chemical synthesis, or the use of prokaryotic expression systems, which often have the disadvantage of requiring subsequent steps to correctly fold the peptide. This paper reports the production of a conotoxin, TxVIA from Conus textile, as a biologically active recombinant protein, using the yeast Pichia pastoris as expression host. The presence of the pro-peptide was found to be necessary for the expression of biologically active conotoxin. We also show that TxVIA is not, as previously reported, mollusc-specific, but also shows insecticidal activity when injected into lepidopteran (cabbage moth) and dipteran (house fly) larvae. In contrast, recombinant TxVIA was not found to be molluscicidal to the grey field slug Deroceras reticulatum.

Insect-resistant biotech crops and their impacts on beneficial arthropods.

With a projected population of 10 billion by 2050, an immediate priority for agriculture is to achieve increased crop yields in a sustainable and cost-effective way. The concept of using a transgenic approach was realized in the mid-1990s with the commercial introduction of genetically modified (GM) crops. By 2010, the global value of the seed alone was US $11.2 billion, with commercial biotech maize, soya bean grain and cotton valued at approximately US $150 billion. In recent years, it has become evident that insect-resistant crops expressing δ-endotoxin genes from Bacillus thuringiensis have made a significant beneficial impact on global agriculture, not least in terms of pest reduction and improved quality. However, because of the potential for pest populations to evolve resistance, and owing to lack of effective control of homopteran pests, alternative strategies are being developed. Some of these are based on Bacillus spp. or other insect pathogens, while others are based on the use of plant- and animal-derived genes. However, if such approaches are to play a useful role in crop protection, it is desirable that they do not have a negative impact on beneficial organisms at higher trophic levels thus affecting the functioning of the agro-ecosystem. This widely held concern over the ecological impacts of GM crops has led to the extensive examination of the potential effects of a range of transgene proteins on non-target and beneficial insects. The findings to date with respect to both commercial and experimental GM crops expressing anti-insect genes are discussed here, with particular emphasis on insect predators and parasitoids.

A venom metalloproteinase from the parasitic wasp Eulophus pennicornis is toxic towards its host, tomato moth (Lacanobia oleracae).

Three genes encoding clan MB metalloproteinases (EpMP1-3) were identified from venom glands of the ectoparasitic wasp Eulophus pennicornis. The derived amino acid sequences predict mature proteins of approximately 46 kDa, with a novel two-domain structure comprising a C-terminal reprolysin domain, and an N-terminal domain of unknown function. EpMP3 expressed as a recombinant protein in Pichia pastoris had gelatinase activity, which was inhibited by EDTA. Injection of recombinant EpMP3 into fifth instar Lacanobia oleracea (host) larvae resulted in partial insect mortality associated with the moult to sixth instar, with surviving insects showing retarded development and growth. EpMP3 is expressed specifically in venom glands. These results suggest that EpMP3 is a functional component of Eulophus venom, which is able to manipulate host development.