The Craniofacial Collaboration UK: Developmental Outcomes in 7- and 10-Year-Old Children With Sagittal Synostosis.

The Craniofacial Collaboration UK (CC-UK) protocol is a shared agreement across the 4 UK Highly Specialist Craniofacial Centres (HSCCs) to conduct robust neurodevelopmental and psychosocial clinical screening for children with craniosynostosis. This agreement allows for the analysis of outcomes of a homogenous sample of children with single suture craniosynostosis (SSC), a frequent limitation of the existing research. The current study is the latest analysis of CC-UK data on behavioral, cognitive, and psychosocial outcomes. The focus of this analysis is 7- and 10-year-olds with nonsyndromic sagittal synostosis (SS) who have undergone primary corrective surgery and completed routine clinical screening at 1 of the 4 HSCCs since the introduction of the CC-UK protocol. Due to changes in clinical pathways, only data from 3 HSCCs is included to preserve homogeneity. Results show that the majority of children with SS fall within the average range across behavioral and neurodevelopmental domains. A notable exception was a task involving perceptual reasoning and visuomotor skills (Block Design). Although this difference was small and the mean score remained within the average range, it suggests some increased risk of subtle difficulty with such skills for children with SS. Across other measures, there was no consistent evidence of any significantly increased risk of poorer outcomes, in line with findings of previous CC-UK papers. Understanding the psychological phenotype of SS is a key research priority for parents and clinicians, and the current study is another step toward achieving this goal.

More than meets the eye: Lid and conjunctival injuries in cases of non-sexual assault are frequently accompanied by non-fatal strangulation.

OBJECTIVE: To determine the associations between lid and conjunctival injuries (LACI), non-fatal strangulation (NFS) and domestic family violence (DFV) in non-sexual assault. METHODS: The present study involves an analysis of LACI in a clinical audit of 85 sequential non-sexual assault presentations. RESULTS: LACI was present in 26.9% of non-sexual assault cases, and 47.4% of LACI patients also experienced NFS. LACI was sustained in the context of DFV in 62.9% of cases. Females made up 69.2% of LACI patients, with those between 14 and 29 years most at risk. Children were present in 12.8% of cases, 78.2% of perpetrators were male and 44.9% of patients had previously been assaulted by the same perpetrator. CONCLUSIONS: LACI is frequently associated with NFS and/or DFV. Since NFS increases future homicide attempts and events more than sixfold, LACI is an important signal about a patient's homicide risk, expanding the dimensions of the care needed. Those experiencing LACI during an assault also need to be referred for comprehensive eye examination as soon as possible. With consent, systematic forensic photography of LACI enables its assessment and documentation, which assists the legal process. These conclusions should drive legislative consideration and reform, plus expanded education for clinicians and police.

Sweet corn phytoglycogen dendrimers as a lyoprotectant for dry-state protein storage.

Protein biotherapeutics typically require expensive cold-chain storage to maintain their fold and function. Packaging proteins in the dry state via lyophilization can reduce these cold-chain requirements. However, formulating proteins for lyophilization often requires extensive optimization of excipients that both maintain the protein folded state during freezing and drying (i.e., "cryoprotection" and "lyoprotection"), and form a cake to carry the dehydrated protein. Here we show that sweet corn phytoglycogens, which are glucose dendrimers, can act as both a protein lyoprotectant and a cake-forming agent. Phytoglycogen (PG) dendrimers from 16 different maize sources (PG1-16) were extracted via ethanol precipitation. PG size was generally consistent at ~70-100 nm for all variants, whereas the colloidal stability in water, protein contaminant level, and maximum density of cytocompatibility varied for PG1-16. 10 mg/mL PG1, 2, 9, 13, 15, and 16 maintained the activity of various proteins, including green fluorescent protein, lysozyme, ß-galactosidase, and horseradish peroxidase, over a broad range of concentrations, through multiple rounds of lyophilization. PG13 was identified as the lead excipient candidate as it demonstrated narrow dispersity, colloidal stability in phosphate-buffered saline, low protein contaminants, and cytocompatibility up to 10 mg/mL in NIH3T3 cell cultures. All dry protein-PG13 mixtures had a cake-like appearance and all frozen protein-PG13 mixtures had a Tg' of ~ -26°C. The lyoprotection and cake-forming properties of PG13 were density-dependent, requiring a minimum density of 5 mg/mL for maximum activity. Collectively these data establish PG dendrimers as a new class of excipient to formulate proteins in the dry state.

Integration of an online application to optimise multi-disciplinary meetings: a retrospective analysis.

BACKGROUND: Multi-disciplinary Meetings (MDM) play a crucial role in complex patient care, involving input from various specialties to formulate evidence-based management plans. However, traditional unidirectional approaches and reliance on manual processes have led to inefficiencies in the MDM pathway. AIMS: This study identified and aimed to improve four critical moments where Information Communication Technologies (ICTs) could enhance the MDM process. Initial referral, information synthesis, meeting presentation and the creation of actionable/auditable items. METHODS: Microsoft Office Forms, a customisable survey platform, was implemented to streamline MDM processes. Forms were created to gather patient information, develop agendas, and track outcomes. Automation through Excel scripting further optimised data organisation and agenda creation. RESULTS: Referrals using Forms takes an average of 7 min and 21 s. Over 15 months the submission time has reduced and is trending towards under 5 min for each referral. The system's scalability has allowed 1744 cases to be discussed over a 15-month period. Active departments using Forms is expanding to seven from two prior to the pilot. CONCLUSION(S): Microsoft Office Forms proved to be a valuable and adaptable tool for MDMs, offering benefits such as streamlined information gathering, real-time collaboration, and scalability. The study highlights the potential of existing tools within Microsoft licenses for healthcare process optimisation, providing a cost-effective and customisable solution for MDM agendas. While recognising some limitations, the study concludes that leveraging Microsoft Office Forms can significantly improve system efficiency in a multi-disciplinary setting.

Phage predation, disease severity, and pathogen genetic diversity in cholera patients.

Despite an increasingly detailed picture of the molecular mechanisms of bacteriophage (phage)-bacterial interactions, we lack an understanding of how these interactions evolve and impact disease within patients. In this work, we report a year-long, nationwide study of diarrheal disease patients in Bangladesh. Among cholera patients, we quantified Vibrio cholerae (prey) and its virulent phages (predators) using metagenomics and quantitative polymerase chain reaction while accounting for antibiotic exposure using quantitative mass spectrometry. Virulent phage (ICP1) and antibiotics suppressed V. cholerae to varying degrees and were inversely associated with severe dehydration depending on resistance mechanisms. In the absence of antiphage defenses, predation was "effective," with a high predator:prey ratio that correlated with increased genetic diversity among the prey. In the presence of antiphage defenses, predation was "ineffective," with a lower predator:prey ratio that correlated with increased genetic diversity among the predators. Phage-bacteria coevolution within patients should therefore be considered in the deployment of phage-based therapies and diagnostics.

Supporting physical activity through co-production in people with severe mental ill health (SPACES): protocol for a randomised controlled feasibility trial.

BACKGROUND: Severe mental ill health (SMI) includes schizophrenia, bipolar disorder and schizoaffective disorder and is associated with premature deaths when compared to people without SMI. Over 70% of those deaths are attributed to preventable health conditions, which have the potential to be positively affected by the adoption of healthy behaviours, such as physical activity. People with SMI are generally less active than those without and face unique barriers to being physically active. Physical activity interventions for those with SMI demonstrate promise, however, there are important questions remaining about the potential feasibility and acceptability of a physical activity intervention embedded within existing NHS pathways. METHOD: This is a two-arm multi-site randomised controlled feasibility trial, assessing the feasibility and acceptability of a co-produced physical activity intervention for a full-scale trial across geographically dispersed NHS mental health trusts in England. Participants will be randomly allocated via block, 1:1 randomisation, into either the intervention arm or the usual care arm. The usual care arm will continue to receive usual care throughout the trial, whilst the intervention arm will receive usual care plus the offer of a weekly, 18-week, physical activity intervention comprising walking and indoor activity sessions and community taster sessions. Another main component of the intervention includes one-to-one support. The primary outcome is to investigate the feasibility and acceptability of the intervention and to scale it up to a full-scale trial, using a short proforma provided to all intervention participants at follow-up, qualitative interviews with approximately 15 intervention participants and 5 interventions delivery staff, and data on intervention uptake, attendance, and attrition. Usual care data will also include recruitment and follow-up retention. Secondary outcome measures include physical activity and sedentary behaviours, body mass index, depression, anxiety, health-related quality of life, healthcare resource use, and adverse events. Outcome measures will be taken at baseline, three, and six-months post randomisation. DISCUSSION: This study will determine if the physical activity intervention is feasible and acceptable to both participants receiving the intervention and NHS staff who deliver it. Results will inform the design of a larger randomised controlled trial assessing the clinical and cost effectiveness of the intervention. TRIAL REGISTRATION: ISRCTN: ISRCTN83877229. Registered on 09.09.2022.

The Craniofacial Collaboration UK: Developmental Outcomes in 7- and 10-Year-Old Children With Metopic Synostosis.

The Craniofacial Collaboration (CC-UK) is a shared initiative across the Psychology teams attached to 4 highly specialized craniofacial centers in the United Kingdom. The CC-UK aims to address key limitations in the existing craniofacial literature by analyzing data for homogenous samples of children with craniosynostosis. This article presents the fifth wave of CC-UK data collection, focused on 7- and 10-year olds who have undergone primary corrective surgery for metopic synostosis (MS). Data for children with sagittal synostosis and MS have previously been presented at 3 and 5 years. This paper continues to build on this with consideration to older age groups, presenting the first CC-UK analysis of cognitive assessment data using the Wechsler Abbreviated Scale of Intelligence-Second Edition. Results show that the majority of children with MS fall within the average ranges across behavioral and neurodevelopmental domains. However, several domains indicated a trend of heightened concern when compared with normative data, particularly for parent-reported outcomes, suggesting that there may be some subtle difficulties for children with MS. Consideration of how these findings compare with that of previous CC-UK analyses is explored. Further, implications for clinical practice and future research are considered, with the need for longitudinal analyses, as well as data from multiple perspectives (eg, school, parents, and self) at older age points to establish patterns over time. Through collaboration across the highly specialized craniofacial centers, the CC-UK hopes to work toward this goal moving forward.

An acyl-CoA thioesterase is essential for the biosynthesis of a key dauer pheromone in C. elegans.

Methyl ketone (MK)-ascarosides represent essential components of several pheromones in Caenorhabditis elegans, including the dauer pheromone, which triggers the stress-resistant dauer larval stage, and the male-attracting sex pheromone. Here, we identify an acyl-CoA thioesterase, ACOT-15, that is required for the biosynthesis of MK-ascarosides. We propose a model in which ACOT-15 hydrolyzes the ß-keto acyl-CoA side chain of an ascaroside intermediate during ß-oxidation, leading to decarboxylation and formation of the MK. Using comparative metabolomics, we identify additional ACOT-15-dependent metabolites, including an unusual piperidyl-modified ascaroside, reminiscent of the alkaloid pelletierine. The ß-keto acid generated by ACOT-15 likely couples to 1-piperideine to produce the piperidyl ascaroside, which is much less dauer-inducing than the dauer pheromone, asc-C6-MK (ascr#2, 1). The bacterial food provided influences production of the piperidyl ascaroside by the worm. Our work shows how the biosynthesis of MK- and piperidyl ascarosides intersect and how bacterial food may impact chemical signaling in the worm.

Phage predation, disease severity and pathogen genetic diversity in cholera patients.

Despite an increasingly detailed picture of the molecular mechanisms of phage-bacterial interactions, we lack an understanding of how these interactions evolve and impact disease within patients. Here we report a year-long, nation-wide study of diarrheal disease patients in Bangladesh. Among cholera patients, we quantified Vibrio cholerae (prey) and its virulent phages (predators) using metagenomics and quantitative PCR, while accounting for antibiotic exposure using quantitative mass spectrometry. Virulent phage (ICP1) and antibiotics suppressed V. cholerae to varying degrees and were inversely associated with severe dehydration depending on resistance mechanisms. In the absence of anti-phage defenses, predation was 'effective,' with a high predator:prey ratio that correlated with increased genetic diversity among the prey. In the presence of anti-phage defenses, predation was 'ineffective,' with a lower predator:prey ratio that correlated with increased genetic diversity among the predators. Phage-bacteria coevolution within patients should therefore be considered in the deployment of phage-based therapies and diagnostics.

High-performance polyimine vitrimers from an aromatic bio-based scaffold.

Bio-based vitrimers represent a promising class of thermosetting polymer materials, pairing the recyclability of dynamic covalent networks with the renewability of non-fossil fuel feedstocks. Vanillin, a low-cost lignin derivative, enables facile construction of polyimine networks marked by rapid exchange and sensitivity to acid-catalyzed hydrolysis. Furthermore, the aromatic structure makes it a promising candidate for the design of highly aromatic networks capable of high-performance thermal and dimensional stability. Such properties are paramount in polymeric thermal protection systems. Here, we report on the fabrication of polyimine networks with particularly high aromatic content from a novel trifunctional vanillin monomer prepared from the nucleophilic aromatic substitution of perfluoropyridine (PFP) on a multi-gram scale (>20 g) in high yield (86%). The trifunctional aromatic scaffold was then crosslinked with various diamines to demonstrate tunable viscoelastic behavior and thermal properties, with glass transition temperatures (Tg) ranging from 9 to 147 °C, degradation temperatures (5% mass loss) up to approximately 370 °C, and excellent char yields up to 68% at 650 °C under nitrogen. Moreover, the vitrimers displayed mechanical reprocessability over five destruction/healing cycles and rapid chemical recyclability following acidic hydrolysis at mild temperatures. Our findings indicate that vitrimers possessing tunable properties and high-performance thermomechanical behavior can be easily constructed from vanillin and electrophilic aromatic scaffolds for applications in heat-shielding materials and ablative coatings.

Physical Activity in Adults with Schizophrenia and Bipolar Disorder: A Large Cross-Sectional Survey Exploring Patterns, Preferences, Barriers, and Motivating Factors.

Adults with severe mental ill health may have specific attitudes toward physical activity. To inform intervention development, we conducted a survey to assess the physical activity patterns, preferences, barriers, and motivations of adults with severe mental ill health living in the community. Data were summarised using descriptive statistics, and logistic regressions were used to explore relationships between physical activity status and participant characteristics. Five-hundred and twenty-nine participants (58% male, mean age 49.3 years) completed the survey. Large numbers were insufficiently active and excessively sedentary. Self-reported levels of physical activity below that recommended in national guidelines were associated with professional inactivity, consumption of fewer than five portions of fruit and vegetables per day, older age, and poor mental health. Participants indicated a preference for low-intensity activities and physical activity that they can do on their own, at their own time and pace, and close to home. The most commonly endorsed source of support was social support from family and friends. Common motivations included improving mental health, physical fitness, and energy levels. However, poor mental and physical health and being too tired were also common barriers. These findings can inform the development of physical activity interventions for this group of people.

Nonpolar Lipids Contribute to Midday Fogging During Scleral Lens Wear.

Purpose: To determine correlations between lipids in the fluid reservoir (FR) and the severity of midday fogging (MDF) in scleral lens (SL) wear. Methods: SL neophytes were recruited to wear custom SL for 4 days, examined after 8 hours on days 1 and 4. Lens vault and MDF were quantified from anterior segment optical coherence tomography (AS-OCT), and the FR was collected and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Relative abundance of lipids was compared to MDF scores using nonparametric correlation testing (Spearman rank). Ocular surface and SL fitting characteristics (lens vault, fitting curves) were likewise compared to MDF. Results: Thirteen participants (26 eyes, 69% female, 28 ± 9 years old) were included in this study. MDF severity after 8 hours of SL wear was 33 ± 29 units on day 1 and 28 ± 24 units on day 4 (r = .94; P < 0.01). Twelve samples were analyzed using LC-MS/MS, and a total of 170 distinct lipid species were detected. The lipid classes with greatest correlation to MDF were the wax esters (r = .73, P = 0.01), cholesteryl esters (r = .59; P = 0.049), and triacylglycerols (r = .64, P = 0.03). Polar lipids were observed abundantly in all samples. None of the measured ocular surface or fitting outcomes were correlated to MDF. Conclusions: Nonpolar lipids were the greatest contributors to MDF among these normal participants. Polar lipids may be due to cellular debris, although they do not appear contributory to MDF.

The Craniofacial Collaboration UK: Developmental Outcomes in 5-Year-Old Children With Metopic Synostosis.

The Craniofacial Collaboration (CC-UK) was setup in 2015 as a joint initiative between the Psychology teams attached to the 4 highly specialized craniofacial centers in the United Kingdom. The CC-UK aims to address key limitations in the existing craniofacial literature by applying strict exclusion criteria and collating clinical data on a homogenous sample of children. This article reports the fourth wave of data collection from the CC-UK, with the analysis of developmental and behavioral outcomes for children with metopic synostosis at 5 years old. Previous data for sagittal synostosis at 3 and 5 years, and metopic synostosis at 3 years, have been presented. This paper offers the first analysis of developmental and behavioral parent-report measures at school age for metopic synostosis. All children in the current data set had primary corrective surgery. Findings highlight similar patterns to that of previous research among children with single-suture craniosynostosis, as well as earlier CC-UK analyses, with the majority falling within 1 standard deviation of the normative mean. However, differences across key behavioral and emotional domains, with some areas reporting heightened concerns compared with those detected among sagittal groups, may suggest that subtle differences between individual diagnostic groups are present. This further highlights the importance of utilizing homogenous samples within the field of craniofacial research. To further build upon this work, and to provide a greater understanding of how these difficulties and concerns may develop, or diminish, over time, further consideration to longitudinal outcomes is needed for individual diagnostic groups. Through this collaboration, the authors seek to achieve this goal in their future work.

Optimization of the Sulfo-Phospho-Vanillin Assay for Total Lipid Normalization in Untargeted Quantitative Lipidomic LC-MS/MS Applications.

Liquid chromatography (LC)-mass spectrometry (MS)/MS lipidomic normalization is generally performed by equalizing pre-extraction sample materials or via DNA or protein pre-quantitation methods, which have known measurement inaccuracies. We propose the use of the sulfo-phospho-vanillin assay (SPVA), a total lipid colorimetric analysis, as a pre-quantitation method to normalize lipids in lipidomic LC-MS/MS applications. The assay has been applied to a 300 µL well volume in a 96-well plate and tested using Avanti total lipid standards of porcine brain and E. coli. Assay parameters for lipid sample volume, sulfuric acid, vanillin/phosphoric acid, post-reaction incubation time, and wavelength are optimized for robust application to biologically sourced lipid samples. Standard test samples were prepared using three concentrations covering approximately 100 µg/mL range. The optimized assay yielded test sample errors less than 10%, indicating a precise and accurate assay performance. The test samples were then analyzed by LC-MS/MS and normalized using SPVA pre-quantitation and pseudo-mass normalization. The detected lipids showed smaller standard deviations and greater relative concentration differences compared to the pseudo-mass normalized lipids, showing promise as a normalization method.

Circadian rhythms in psoriasis and the potential of chronotherapy in psoriasis management.

The physiology and pathology of the skin are influenced by daily oscillations driven by a master clock located in the brain, and peripheral clocks in individual cells. The pathogenesis of psoriasis is circadian-rhythmic, with flares of disease and symptoms such as itch typically being worse in the evening/night-time. Patients with psoriasis have changes in circadian oscillations of blood pressure and heart rate, supporting wider circadian disruption. In addition, shift work, a circadian misalignment challenge, is associated with psoriasis. These features may be due to underlying circadian control of key effector elements known to be relevant in psoriasis such as cell cycle, proliferation, apoptosis and inflammation. Indeed, peripheral clock pathology may lead to hyperproliferation of keratinocytes in the basal layers, insufficient apoptosis of differentiating keratinocytes in psoriatic epidermis, dysregulation of skin-resident and migratory immune cells and modulation of angiogenesis through circadian oscillation of vascular endothelial growth factor A (VEGF-A) in epidermal keratinocytes. Chronotherapeutic effects of topical steroids and topical vitamin D analogues have been reported, suggesting that knowledge of circadian phase may improve the efficacy, and therapeutic index of treatments for psoriasis. In this viewpoint essay, we review the current literature on circadian disruption in psoriasis. We explore the hypothesis that psoriasis is circadian-driven. We also suggest that investigation of the circadian components specific to psoriasis and that the in vitro investigation of circadian regulation of psoriasis will contribute to the development of a novel chronotherapeutic treatment strategy for personalised psoriasis management. We also propose that circadian oscillations of VEGF-A offer an opportunity to enhance the efficacy and tolerability of a novel anti-VEGF-A therapeutic approach, through the timed delivery of anti-VEGF-A drugs.

Imaging Biomarkers in Prostate Stereotactic Body Radiotherapy: A Review and Clinical Trial Protocol.

Advances in imaging have changed prostate radiotherapy through improved biochemical control from focal boost and improved detection of recurrence. These advances are reviewed in the context of prostate stereotactic body radiation therapy (SBRT) and the ARGOS/CLIMBER trial protocol. ARGOS/CLIMBER will evaluate 1) the safety and feasibility of SBRT with focal boost guided by multiparametric MRI (mpMRI) and 18F-PSMA-1007 PET and 2) imaging and laboratory biomarkers for response to SBRT. To date, response to prostate SBRT is most commonly evaluated using the Phoenix Criteria for biochemical failure. The drawbacks of this approach include lack of lesion identification, a high false-positive rate, and delay in identifying treatment failure. Patients in ARGOS/CLIMBER will receive dynamic 18F-PSMA-1007 PET and mpMRI prior to SBRT for treatment planning and at 6 and 24 months after SBRT to assess response. Imaging findings will be correlated with prostate-specific antigen (PSA) and biopsy results, with the goal of early, non-invasive, and accurate identification of treatment failure.