Patient and Public Involvement (PPI) and Responsible Research and Innovation (RRI) approaches in mental health projects involving young people: a scoping review protocol.

BACKGROUND: Rather than being perceived as merely 'part of the problem', the perspectives and experiences of young people play a pivotal role in devising effective solutions for mental health challenges. Two distinct methodologies that aid in this endeavour are 'patient and public involvement' (PPI) and 'responsible research and innovation' (RRI). However, there is a tendency to conflate PPI and RRI practices, leading to ambiguity in their application. Moreover, the extent and nature of young people's involvement in mental health-related projects (namely: research, intervention, product development) employing these methodologies, and the subsequent implications thereof, remain unclear. Consequently, the proposed scoping review aims to identify and analyse literature pertaining to PPI and RRI approaches in mental health projects that engage young people in collaboration. METHODS: The selected databases will be MEDLINE, PsycINFO, PsycArticles, Scopus, Web of Science, IBBS, CINAHL (EBSCO) and ASSIA. Comprehensive searches will span from the inception of each database. A pilot test will be conducted to assess the screening criteria and data extraction form, with two authors independently reviewing titles and abstracts. Full-text articles meeting the inclusion criteria will undergo narrative syntheses, with results presented in tabular format. Feedback on the findings from a youth perspective will be sought from young people within our broader research network, namely Sprouting Minds. The review will adhere to the guidelines outlined by the Joanna Briggs Institute (JBI) and follow the PRISMA-ScR procedures. Inclusion criteria will comprise English-language, primary research peer-reviewed articles focused on Patient and Public Involvement (PPI) or Responsible Research and Innovation (RRI), examining mental health-related research processes, interventions, and products developed in collaboration with young people. Studies employing quantitative, qualitative, and mixed-methods approaches will be considered, while non-journal publications will be excluded. DISCUSSION: The intended scoping review aims to map the literature concerning mental health-related projects that engage with young people through PPI or RRI approaches. The outcomes hold promise for enriching the participatory research domain, particularly in studies centred on young people and their mental well-being. Furthermore, by delineating potential overlaps and distinctions between PPI and RRI, the findings stand to aid mental health researchers and practitioners in making informed decisions about the most suitable approach for their projects when partnering with young individuals. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework (registration: DOI https://doi.org/10.17605/OSF.IO/N4EDB ).

This study aims to understand how young people are involved in mental health projects (namely: research, intervention, and product development) and how their perspectives shape the outcomes. Two approaches, Patient and Public Involvement (PPI) and Responsible Research and Innovation (RRI), are often used in these projects, but it's not clear how they differ or how young people are involved. To explore this, the researchers will review existing literature on mental health projects involving young people. They will search databases for articles that describe or evaluate these projects, focusing on how young people are involved in the research and/or development processes. They will include studies in English that have been peer-reviewed and cover both numerical and text-based research. Young people will be involved to provide feedback from their perspective. This review will follow established guidelines to ensure trustworthiness and transparency. The findings from this review will help researchers and professionals understand the best ways to involve young people in mental health projects. By clarifying the differences between PPI and RRI and highlighting effective strategies, this study aims to improve future research and ultimately benefit young people's mental health.

The effect of diabetes management on the workload of district and community nursing teams in the UK.

AIMS: The number of older people with diabetes requiring care from district nursing teams is increasing. The role of district nursing teams in diabetes management has expanded to involve diagnosis, treatment and medication administration. As the complexity of caseloads increases, the current model is likely unsustainable. This study aims to understand the current diabetes workload of district nursing teams. METHODS: An online survey was distributed via social media and key stakeholder networks to district nursing teams. Survey items were designed by the researchers prior to pilot testing with potential participants. Descriptive statistical and qualitative analyses were conducted. Data are median ± IQR. RESULTS: 159 district nursing teams completed the survey. The median caseload per team was 300 (IQR 176-407) patients including 21 with diabetes (IQR 14-40; 8.7% (4-20%)). 1.09 home visits per day per person with diabetes lasting 13.8 minutes (excluding travel time) were needed, with most requiring insulin administration. 96% of nursing teams undertake multiple daily visits for some patients. 91% reported workloads relating to diabetes management had increased over the last 2 years; 76% stated current diabetes workloads were unsustainable. More insulin usage, more referrals and a lack of ability or willingness to self-administer insulin has increased the diabetes workload. Possible solutions include better collaboration between healthcare professionals, simplification of insulin administration and glucose monitoring, better training and upskilling of healthcare assistants and promotion of self-efficacy. CONCLUSIONS: Diabetes management forms an increasing component of district nursing workload and is likely to be unsustainable unless new models are found.

Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo.

Only praziquantel is available for treating schistosomiasis, a disease affecting more than 200 million people. Praziquantel-resistant worms have been selected for in the lab and low cure rates from mass drug administration programs suggest that resistance is evolving in the field. Thioredoxin glutathione reductase (TGR) is essential for schistosome survival and a validated drug target. TGR inhibitors identified to date are irreversible and/or covalent inhibitors with unacceptable off-target effects. In this work, we identify noncovalent TGR inhibitors with efficacy against schistosome infections in mice, meeting the criteria for lead progression indicated by WHO. Comparisons with previous in vivo studies with praziquantel suggests that these inhibitors outperform the drug of choice for schistosomiasis against juvenile worms.

Modelling the dynamics of senescence spread.

Cellular senescence is a cell surveillance mechanism that arrests the cell cycle in damaged cells. The senescent phenotype can spread from cell to cell through paracrine and juxtacrine signalling, but the dynamics of this process are not well understood. Although senescent cells are important in ageing, wound healing and cancer, it is unclear how the spread of senescence is contained in senescent lesions. In the absence of the immune system, senescence could theoretically spread infinitely from one cell to another, but this contradicts experimental evidence. To investigate this issue, we developed both a minimal mathematical model and a stochastic simulation of senescence spread. Our results suggest that differences in the number of signalling molecules secreted between subtypes of senescent cells can limit the spread of senescence. We found that dynamic, time-dependent paracrine signalling prevents the uncontrolled spread of senescence, and we demonstrate how model parameters can be determined using Bayesian inference in a proposed experiment.

Rapid Testing of Resistance of Timber to Biodegradation by Marine Wood-Boring Crustaceans.

Wood-boring invertebrates rapidly destroy marine timbers and wooden coastal infrastructure, causing billions of dollars of damage around the globe every year. As treatments of wood with broad spectrum biocides, such as creosote and chromated copper arsenate (CCA), are now restricted in marine use by legislation, naturally durable timber species and novel preservation methods of wood are required. These methods undergo testing in order to meet regulatory standards, such as the European standard for testing wood preservatives against marine borers, EN 275. Initial investigation of durable timbers species or wood preservative treatments can be achieved quickly and inexpensively through laboratory testing, which offers many advantages over marine field trials that are typically costly, long-term endeavours. Many species of Limnoria (gribble) are marine wood-boring crustaceans. Limnoria are ideal for use in laboratory testing of biodegradation of wood by marine wood-borers, due to the practicality of rearing them in aquaria and the ease of measuring their feeding rates on wood. Herein, we outline a standardizable laboratory test for assessing wood biodegradation using gribble.

The professional resilience of mid-career GPs in the UK: a qualitative study.

BACKGROUND: With a continued crisis of increasing workload and reduced workforce in general practice, supporting resilience is a key strategy for sustaining the profession into the future. AIM: How do GPs perceive professional resilience, and what workplace factors influence it? DESIGN AND SETTING: A UK-based qualitative study of the perspectives of GPs currently practicing in mainly urban locations across the UK with ≥5 years' experience after completion of GP training. METHOD: Participants were recruited using convenience sampling, which included social media forums, and underwent semi-structured interviews undertaken in May and June 2020 (n = 27). Data were analysed using thematic analysis. RESULTS: Participants offered definitions of and influences on resilience that largely fit with existing research, but in addition, may result in the perception that GPs are obstructive, or that resilience may be a 'surface act'. GPs agree that the current focus on methods of improving resilience does support them, but there is significantly more to be done in this field. Social media activity aiming at GP support may be counterproductive. Reduction of clinical working hours is a common strategy to improve resilience. CONCLUSION: That GPs feel to improve resilience they need to work fewer clinical hours may have huge implications for a workforce already in crisis, and ultimately, for the health care of the UK population. Urgent research is needed to formulate a bespoke assessment for measuring GP resilience to assess potential interventions, and to identify GPs at risk of mental ill-health or leaving the profession.

Induction and expression of GluA1 (GluR-A)-independent LTP in the hippocampus.

Long-term potentiation (LTP) at hippocampal CA3-CA1 synapses is thought to be mediated, at least in part, by an increase in the postsynaptic surface expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptors induced by N-methyl-d-aspartate (NMDA) receptor activation. While this process was originally attributed to the regulated synaptic insertion of GluA1 (GluR-A) subunit-containing AMPA receptors, recent evidence suggests that regulated synaptic trafficking of GluA2 subunits might also contribute to one or several phases of potentiation. However, it has so far been difficult to separate these two mechanisms experimentally. Here we used genetically modified mice lacking the GluA1 subunit (Gria1(-/-) mice) to investigate GluA1-independent mechanisms of LTP at CA3-CA1 synapses in transverse hippocampal slices. An extracellular, paired theta-burst stimulation paradigm induced a robust GluA1-independent form of LTP lacking the early, rapidly decaying component characteristic of LTP in wild-type mice. This GluA1-independent form of LTP was attenuated by inhibitors of neuronal nitric oxide synthase and protein kinase C (PKC), two enzymes known to regulate GluA2 surface expression. Furthermore, the induction of GluA1-independent potentiation required the activation of GluN2B (NR2B) subunit-containing NMDA receptors. Our findings support and extend the evidence that LTP at hippocampal CA3-CA1 synapses comprises a rapidly decaying, GluA1-dependent component and a more sustained, GluA1-independent component, induced and expressed via a separate mechanism involving GluN2B-containing NMDA receptors, neuronal nitric oxide synthase and PKC.

Reticulated telangiectatic erythema of the pacemaker.

Reticulated telangiectatic erythema is a rare entity; it has been reported to occur following the placement of implanted cardiac devices and drug delivery systems. Histologically, reticulated telangiectatic erythema of the pacemaker is characterized by slight spongiosis and increased dermal telangiectasias. We describe a patient that developed reticulated telangiectatic nonpruritic patches on the left chest after the placement of a pacemaker. The patient responded favorably to the removal of the pacemaker.

Open-label pilot study of alitretinoin gel 0.1% in the treatment of photoaging.

Alitretinoin (9-cis-retinoic acid) is an FDA-approved topical therapy for the treatment of Kaposi sarcoma. Alitretinoin is a naturally occurring endogenous retinoid that binds to and activates all known intracellular retinoic acid receptor (RAR) subtypes alpha, beta, and gamma and retinoic X receptor (RXR) subtypes alpha, beta, and gamma. Photoaging of the skin is the result of accumulated exposure to solar UV radiation. Several topically applied retinoids have been proven clinically effective for treating the appearance of photoaging. Tretinoin and tazarotene, which have been shown to improve photodamaged skin, bind RAR subtypes only. The theoretic benefit of alitretinoin gel 0.1% (Panretin) in the treatment of photoaged skin stems from the binding and activation of both RARs and RXRs, which promote the repair mechanisms in damaged skin. The objective of this study was to evaluate the safety and efficacy of topical alitretinoin gel 0.1% in the treatment of photodamaged skin. The treatment was well tolerated by participants (N=20) and subjectively showed improvement of benign skin lesions (eg, seborrheic keratoses) and precancerous lesions (eg, actinic keratoses). Larger, blinded, controlled trials are needed to investigate the role of this novel retinoid in the treatment of photoaging.

Pilot study of the safety and efficacy of Myobloc (botulinum toxin type B) for treatment of axillary hyperhidrosis.

BACKGROUND: Botulinum toxin type B (BTX-B, Myobloc, San Francisco, CA, USA) was FDA-approved for the treatment of cervical dystonia in December 2000. It has since been used off-label for the treatment of axillary hyperhidrosis. However, there are sparse data in the medical literature evaluating the safety and efficacy of Myobloc (botulinum toxin type B) for this indication. OBJECTIVE: To assess the safety, efficacy and duration of action of Myobloc (botulinum toxin type B) in the treatment of bilateral axillary hyperhidrosis. METHODS: This study was a double-blinded, randomized, pilot study conducted in an outpatient office setting at a private academic medical center beginning in November 2001. Twenty-three male and female volunteers between the ages of 18 and 80 were screened for participation; 20 participants with primary axillary hyperhidrosis were enrolled. Participants were injected subcutaneously with either Myobloc (botulinum toxin type B) (2500 U, or 0.5 ml, per axilla) or 0.5 ml vehicle (100 mM NaCl, 10 mM succinate, and 0.5 mg/ml human albumin) into bilateral axillae. Participants who received placebo were rolled over and received Myobloc (botulinum toxin type B) at subsequent visits. All participants were followed until sweating returned to baseline levels. This trial was initially conceived as a placebo-controlled study; however, owing to the insufficient size of the placebo group, the placebo arm of this trial was dropped during data analysis. The main outcome measures were safety, efficacy, and duration of effect. RESULTS: According to participant assessment of axillary hyperhidrosis improvement (A-HI) and quality of life (A-HQOL) scores and the physician assessment scores, a significant difference was observed in treatment response at Day 30 in the participants receiving Myobloc (botulinum toxin type B) injections. Duration of action ranged from 2.2 to 8.1 months (mean 5.0 months). The adverse event profile included bruising, flu-like symptoms, and dry eyes. CONCLUSION: Myobloc (botulinum toxin type B) proved to be safe and efficacious for the treatment of bilateral axillary hyperhidrosis. More studies are needed to assess the duration of response using different doses of Myobloc (botulinum toxin type B).

Double-blind, randomized, placebo-controlled pilot study of the safety and efficacy of Myobloc (botulinum toxin type B) for the treatment of palmar hyperhidrosis.

BACKGROUND: Palmar hyperhidrosis is a problem of unknown etiology that affects patients both socially and professionally. Botulinum toxin type B (Myobloc), approved by the Food and Drug Administration for use in the treatment of cervical dystonia in the United States in December 2000, has subsequently been used effectively in an off-label indication to treat hyperhidrosis. There are sparse data, however, in the literature evaluating the safety and efficacy of BTX-B for the treatment of palmar hyperhidrosis. OBJECTIVE: We evaluated the safety and efficacy of Myobloc in the treatment of bilateral palmar hyperhidrosis. This was a double-blind, randomized, placebo-controlled study to report on the safety and efficacy of Myobloc. METHODS: Twenty participants (10 men, 10 women) diagnosed with palmar hyperhidrosis were injected with either Myobloc (5,000 U per palm) or a 1.0 mL vehicle (100 mM NaCl, 10 mM succinate, and 0.5 mg/mL human albumin) into bilateral palms (15 Myobloc, 5 placebo). The participants were followed until sweating returned to baseline levels. The main outcome measures were safety, efficacy versus placebo, and duration of effect. RESULTS: A significant difference was found in treatment response at day 30, as determined by participant assessments, between 15 participants injected with Myobloc and 3 participants injected with placebo. The duration of action, calculated in the 17 participants who received Myobloc injections and completed the study, ranged from 2.3 to 4.9 months, with a mean duration of 3.8 months. The single most reported adverse event was dry mouth or throat, which was reported by 18 of 20 participants. The adverse event profile also included indigestion or heartburn (60%), excessively dry hands (60%), muscle weakness (60%), and decreased grip strength (50%). CONCLUSION: Myobloc proved to be efficacious for the treatment of palmar hyperhidrosis. Myobloc had a rapid onset, with most participants responding within 1 week. The duration of action ranged from 2.3 to 4.9 months, with a mean of 3.8 months. The adverse event profile included dry mouth, indigestion or heartburn, excessively dry hands, muscle weakness, and decreased grip strength.

Telangiectasia macularis eruptiva perstans with an associated myeloproliferative disorder.

Telangiectasia macularis eruptiva perstans (TMEP) is a cutaneous form of mastocytosis. It has been rarely associated with an underlying myeloproliferative disorder. We report the case of a patient, while receiving treatment for thrombocytosis, with both platelet production and function inhibitors presented with TMEP. TMEP is often refractory to therapy; however, our patient responded to treatment with PUVA.

Non-science majors gain valuable insight studying clinical trials literature: an evidence-based medicine library assignment.

When faced with a diagnosis, it is empowering to be able to assess the evidence of treatment effectiveness and safety. To teach this skill to non-science majors, we assigned the "Responsible Patienthood Project" (RPP). For the RPP, students studied an array of disease and treatment literature: the final product of their work was a poster presentation, in which they did an in-depth analysis of one primary article, thus encouraging critical evaluation of experimental design, methods, and conclusions. Post-RPP, there was a 35% decrease in the student perception that they would unquestioningly accept a recommended treatment for a hypothetical diagnosis, and a 40% increase in the perception that they would consult a combination of resources, including primary articles. We recommend this project based on our results that suggest 1) non-science majors are able to successfully access and assess primary scientific literature, 2) students felt empowered by the RPP, and 3) skills in information gathering, via library instruction, may serve as a particularly helpful lifelong learning tool.

Cutaneous Wegener's granulomatosis (malignant pyoderma) in a patient with Crohn's disease.

We report a case of an unusual presentation of Wegener's granulomatosis (WG) in a patient with Crohn's disease (CD). She presented to our Wound Care Center with 7th cranial nerve palsy and facial pyoderma-like ulcerations. Although WG has a predilection for the lung, kidney, and eyes, cutaneous involvement can be seen in 50% of the cases, and it can be the presenting sign in 9-14%. Because of the lethality of WG if not properly treated, the diagnosis is imperative.

Ulcers caused by bullous morphea treated with tissue-engineered skin.

Bullous morphea is an uncommon form of localized scleroderma. The exact pathogenesis is unknown and treatment of the accompanying ulcers is problematic. We report a patient with bullous morphea with long-standing ulcers whom we successfully treated with the tissue-engineered skin Apligraf (Organogenesis Inc., Canton, MA). The patient experienced rapid improvement in granulation tissue and the ulcers healed 4 months after a single application. The rationale for the use of Apligraf is based on experience with patients with venous ulcers who have surrounding peri-ulcer fibrosis. This condition, termed lipodermatosclerosis, has been reported as a poor prognostic factor for healing, yet many ulcers associated with lipodermatosclerosis may respond to treatment with tissue-engineered skin. Taken in concert, these results suggest a role for tissue- engineered skin in the treatment of chronic wounds with surrounding fibrosis.

Allelic phasing of a mouse chromosome 11 deficiency influences p53 tumorigenicity.

Most tumour suppressor genes (TSGs) have been found through linkage studies in cancer predisposed families where the mutations have a high penetrance, for example, the breast cancer genes BRCA1 and BRCA2. Loss of heterozygosity (LOH) analyses of sporadic breast tumours indicate that there are many other putative TSGs yet to be identified. One such locus is proximal to BRCA1 on human chromosome 17q21. In an attempt to isolate this putative TSG, we have assessed a portion of the orthologous region on mouse chromosome 11 for its tumorigenic potential using segmental haploidy in combination with a p53 mutation. Two populations of animals were studied, with the deleted region being either on the same (cis) or on the homologous chromosome (trans) to a targeted mutant p53 allele. The deficiency elevated the tumour susceptibility of p53 heterozygous mice and modified the tumour spectrum, but only when the deficiency was in trans with the p53 mutation. Even though the genotype of these mice is identical, allelic phasing affects both the tumour spectrum and progression.