Bifid Pupil Iridodialysis Secondary to Airsoft Gun Injury.

This case report describes a diagnosis of iridodialysis in an 11-year-old boy who presented with decreased vision and inflammation after direct blunt trauma to the left eye.

Clinical Outcomes in Scleral Fixation Secondary Intraocular Lens with Yamane versus Suture Techniques: A Systematic Review and Meta-Analysis.

Background: The purpose of the study is to compare the visual outcomes and complications of sutured scleral fixation (SSF), a traditional and conservative surgical approach, and the newer and faster Yamane technique for secondary intraocular lens placement. Methods: A literature search was performed on PubMed, Embase, and Scopus on studies published between 1 July 2017 to 29 September 2023. Outcomes analyzed included the final best corrected visual acuity (BCVA) between 3 and 12 months to assess the effectiveness of the procedure, post-operative month (POM) 1 BCVA to assess the speed of visual recovery, endothelial cell count (ECC), absolute refractive error, surgical duration, and complication rates. Additional subgroup analyses were performed based on surgeon experience with the technique. Single-surgeon studies had an average of 26 procedures performed, whereas multiple-surgeon studies averaged only 9 procedures performed; these were then used to delineate surgeon experience. A sample-size weighted mean difference (MD) meta-analysis was performed across all variables using RevMan 5.4.1; p < 0.05 was considered statistically significant. Results: Thirteen studies with 737 eyes were included: 406 eyes were included in the SSF group, and 331 eyes were included in the Yamane group. There was no significant difference in the final BCVA between groups in both the single-surgeon versus multiple-surgeon studies (MD = -0.01, 95% CI: [-0.06, 0.04], p = 0.73). In the single-surgeon studies, the BCVA at POM1 was significantly improved in the Yamane group compared to SSF (MD = -0.10, 95% CI: [-0.16, -0.04], p = 0.002). In the multiple-surgeon studies, there was no significant difference in BCVA at POM1 (MD = -0.06, 95% CI: [-0.16, 0.04], p = 0.23). The Yamane group had a shorter surgical duration than SSF in both single-surgeon and multiple-surgeon studies (MD = -24.68, 95% CI: [-35.90, -13.46], p < 0.0001). The ECC, refractive error, and complication rates did not significantly differ amongst all groups. Conclusions: The Yamane technique demonstrated similar long-term visual outcomes and complication rates to the traditional SSF. Visual recovery was significantly faster in the Yamane group in the single-surgeon studies. The operative times were shorter across all Yamane groups. Based on these findings, it is advisable to consider the Yamane technique as a viable, and perhaps preferable, option for patients requiring secondary IOL placement, alongside traditional SSF methods.

Experiences and Acceptability of a Weight Loss Intervention for Diabetes (Diabetes Remission Clinical Trial-DiRECT) in Aotearoa New Zealand: A Qualitative Study within a Pilot Randomised Controlled Trial.

The Diabetes Remission Clinical Trial (DiRECT) demonstrated that substantial weight loss and remission from type 2 diabetes can be achieved with low-energy total diet replacement and behavioural support. However, the acceptability of the DiRECT intervention in diverse populations with strong cultural emphases on food and shared eating remains unclear. We conducted a qualitative study nested within a pilot randomised controlled trial of DiRECT in one Maori (the Indigenous people of New Zealand) primary care provider in Aotearoa New Zealand. Participants with type 2 diabetes or prediabetes, obesity, and a desire to lose weight were randomised to either dietitian-supported usual care or the dietitian-supported DiRECT intervention for twelve months. The DiRECT intervention included three months of total diet replacement, then food reintroduction and supported weight loss maintenance. At three and twelve months, semi-structured interviews explored the acceptability of DiRECT and participants' experiences of each intervention. Interview transcripts from 25 participants (aged 48 ± 10 years, 76% female, 78% Maori or Pacific) at three months and 15 participants at twelve months were analysed. Participants viewed their pre-enrolment selves as unhealthy people with poor eating habits and desired professional weight loss support. For DiRECT participants, the total diet replacement phase was challenging but well-received, due to rapid improvements in weight and health. Food reintroduction and weight loss maintenance each presented unique challenges requiring effective strategies and adaptability. All participants considered individualised and empathetic dietetic support crucial to success. Sociocultural factors influencing success were experienced in both interventions: family and social networks provided support and motivation; however, eating-related norms were identified as challenges. The DiRECT intervention was considered an acceptable approach to weight loss in participants with type 2 diabetes or prediabetes with strong cultural emphases on food and shared eating. Our findings highlight the importance of individualised and culturally relevant behavioural support for effective weight loss and weight loss maintenance.

Aptamer-assisted phage display: enhancing checkpoint inhibition with a peptide and an aptamer targeting distinct sites on a single PD-L1 protein.

Utilizing a novel approach known as aptamer-assisted phage display (APD), we identified an anti-PD-L1 peptide, NV Pep, capable of simultaneous binding to PD-L1 alongside the DNA aptamer MJ5C. Combined inhibition using NV Pep and MJ5C demonstrated significant enhancement compared to individual ligands against the PD-1/PD-L1 interaction.

The effect of teprotumumab infusion on ocular alignment in patients with symptomatic thyroid eye disease.

BACKGROUND: Thyroid eye disease (TED) can result in proptosis and ocular misalignment, leading to eye pain, diplopia, and vision loss. Teprotumumab, a humanized antibody against insulin-like growth factor 1 receptor, was approved in 2020 for the treatment of TED. The purpose of this study was to describe the effect of a full course of teprotumumab on ocular misalignment. METHODS: The medical records of patients who underwent treatment with teprotumumab for active moderate-to-severe TED at a single institution from April 2020 to September 2023 were reviewed retroactively. Sensorimotor examination was performed at each visit using simultaneous prism-cover testing. Demographic information and previous history of radioactive iodine, steroids, strabismus surgery, and smoking were extracted from the record for analysis. RESULTS: A total of 19 patients were treated during the study period, of whom 11 had strabismus and diplopia. The initial absolute horizontal misalignment in these 11 was 6.0Δ ± 1.5Δ, vertical misalignment was 7.7Δ ± 2.4Δ, and total misalignment was 11.5Δ ± 2.0Δ. On completion of treatment, these measurements decreased by 2.0Δ ± 1.5Δ, 2.2Δ ± 1.0Δ, and 3.2Δ ± 1.6Δ, respectively (P = 0.10, 0.02, and 0.04, resp.). Eight patients (73%) had a decrease in their strabismus, and 5 (46%) reported complete resolution of their diplopia at the final visit. No factors were predictive of which patients would have resolution of their misalignment. Of the remaining 3 patients who had no improvement in ocular alignment, 2 (66%) underwent strabismus surgery. Of the 8 patients with improvement of strabismus, only a single patient (13%) underwent strabismus surgery for persistent diplopia. CONCLUSIONS: In our study cohort, a full course of teprotumumab coincided with complete resolution of diplopia in 46% of patients and a decrease in strabismus in 73% of patients.

Volatile phenols in wine: overview of origin, formation, analysis, and sensory expression.

Volatile phenols impart particular aromas to wine. Due to their distinctive aroma characteristics and low sensory thresholds, volatile phenols can easily influence and modify the aroma of wine. Since these compounds can be formed in wines in various ways, it is necessary to clarify the possible sources of each volatile phenol to achieve management during the winemaking process. The sources of volatile phenols in wine are divided into berry-derived, fermentation-derived, and oak-derived. The pathways and factors influencing the formation of volatile phenols from each source are then reviewed respectively. In addition, an overview of the sensory impact of volatile phenols is given, both in terms of the aroma these volatile phenols directly bring to the wine and their contribution through aroma interactions. Finally, as an essential basis for exploring the scientific problems of volatile phenols in wine, approaches to quantitation of volatile phenols and their precursors are discussed in detail. With the advancement of analytical techniques, more details on volatile phenols have been discovered. Further exploration is worthwhile to achieve more detailed monitoring and targeted management of volatile phenols in wine.

The broader health benefits of optimised dietary thresholds proposed for type 2 diabetes prevention in Aotearoa New Zealand: simulation modelling.

AIM: Optimised dietary thresholds for type 2 diabetes prevention exist; however, they likely have additional benefits beyond diabetes prevention. We have modelled the effects of the proposed dietary thresholds on Health-Adjusted Life Years (HALY), health inequities and health system cost in Aotearoa New Zealand. METHODS: We created a national diet scenario using the optimised thresholds and compared it with current intakes using an established multistate life table. The primary model considered change in outcome from increasing intakes of fruits, vegetables, nuts and seeds while decreasing red meat and sugar-sweetened beverages. A separate secondary nutrient-based model considered change due to increasing whole grains and yoghurt while decreasing refined grains, potatoes and fruit juice. Both models considered the direct non-weight mediated associations between diet and disease. RESULTS: In the primary model, adopting the dietary thresholds produced clear benefit to Aotearoa New Zealand in terms of HALY (1.2 million years [95%UI 1.0-1.5]), and a health system cost saving of $17.9 billion (95%UI 13.6-23.2) over the population life course. HALY gain was at least 1.8 times higher for Maori than non-Maori. The secondary model indicated further gains in HALY for all population groups and health systems costs. CONCLUSION: These striking benefits of altering current dietary intakes provide strong evidence of the need for change. Such change requires government commitment to an overarching food strategy in Aotearoa New Zealand to build supportive food environments that enable healthy choices at affordable prices.

Healthy grocery delivery in the usual care for adults recovering from an acute coronary event: protocol for a three-arm randomised controlled trial.

INTRODUCTION: Coronary heart disease is a major contributor to the global burden of disease. Appropriate nutrition is a cornerstone of the prevention and treatment of coronary heart disease; however, barriers including cost and access to recommended foods limits long-term adherence for many. We are conducting, in adults with coronary heart disease, a randomised controlled trial comparing usual care with two dietary interventions in which usual care is augmented by 12 weeks free delivered groceries. METHODS AND ANALYSIS: Three hundred adults recovering from an acute coronary event will be recruited from outpatient cardiovascular services in three regions of Aotearoa New Zealand. Participants will be randomly allocated to three arms: usual care (control group), usual care and the free delivery of foods high in dietary fibre or usual care and the free delivery of foods high in unsaturated fats. Interventions duration is 12 weeks, with a further 12 months follow-up. The primary outcome measures are change in low-density lipoprotein (LDL) cholesterol concentration following the intervention, and a cost-effectiveness analysis of healthcare access and social costs in the year after the intervention. A broad range of secondary outcome measures include other blood lipids, anthropometry, glycaemia, inflammatory markers, gut microbiome, dietary biomarkers, food acceptability, dietary change and the facilitators and barriers to dietary change. The trial will determine whether the free provision of groceries known to reduce cardiovascular risk within usual care will be clinically beneficial and justify the cost of doing so. Results may also provide an indication of the relative benefit of foods rich in dietary fibre or unsaturated fats in coronary heart disease management. ETHICS AND DISSEMINATION: This trial, The Healthy Heart Study, has Health and Disability Ethics Committee approval (20/NTB/121), underwent Maori consultation, and has locality authority to be conducted in Canterbury, Otago and Southland. TRIAL REGISTRATION NUMBER: ACTRN12620000689976, U1111-1250-1499.

Ni aptamer: DNA mimic of His-tag to recognize Ni-NTA.

We introduced Ni Apt as the first aptamer with a characterized dissociation constant for recognizing Ni-NTA. Serving as a nucleic acid analog of the His-tag commonly employed for protein purification using Ni-NTA resin, Ni Apt displays a remarkable binding affinity (Kd = 106 nM) towards Ni-NTA. Furthermore, it can be eluted from the resin using imidazole or EDTA, similar to the removal of His-tag from Ni-NTA resin. The versatile capabilities of Ni Apt make it a valuable molecular tool in nucleic acid purification and recognition applications.

Antibiotic prophylaxis dysregulates dental implant placement surgery-induced osteoimmune wound healing and attenuates the alveolar bone-implant interface in mice.

AIM: Antimicrobial-induced shifts in commensal oral microbiota can dysregulate helper T-cell oral immunity to affect osteoclast-osteoblast actions in alveolar bone. Antibiotic prophylaxis is commonly performed with dental implant placement surgery to prevent post-surgical complications. However, antibiotic prophylaxis effects on osteoimmune processes supporting dental implant osseointegration are unknown. The aim of the study was to discern the impact of antibiotic prophylaxis on dental implant placement surgery-induced osteoimmune wound healing and osseointegration. MATERIALS AND METHODS: We performed SHAM or dental implant placement surgery in mice. Groups were administered prophylactic antibiotics (amoxicillin or clindamycin) or vehicle. Gingival bacteriome was assessed via 16S sequencing. Helper T-cell oral immunity was evaluated by flow cytometry. Osteoclasts and osteoblasts were assessed via histomorphometry. Implant osseointegration was evaluated by micro-computed tomography. RESULTS: Dental implant placement surgery up-regulated TH 1, TH 2 and TREG cells in cervical lymph nodes (CLNs), which infers helper T-cell oral immunity contributes to dental implant placement osseous wound healing. Prophylactic antibiotics with dental implant placement surgery caused a bacterial dysbiosis, suppressed TH 1, TH 2 and TREG cells in CLNs, reduced osteoclasts and osteoblasts lining peri-implant alveolar bone, and attenuated the alveolar bone-implant interface. CONCLUSIONS: Antibiotic prophylaxis dysregulates dental implant placement surgery-induced osteoimmune wound healing and attenuates the alveolar bone-implant interface in mice.

The effects of wholegrain processing on appetite: randomised crossover trial in adults with type 2 diabetes.

Aims: Recent observational data indicate higher ultra-processed food intakes are associated with a broad range of adverse health outcomes. Experimental studies on why this might be are lacking. We have considered the effects of wholegrain processing on measures of appetite in free-living adults with type 2 diabetes. Materials and methods: Participants were randomised to two interventions of two-weeks duration, separated by washout. Interventions were nutrient-matched wholegrain foods that differed by the amount of processing. Self-reported hunger and satiety were indicated on visual analogue scales before or after meals for four days at baseline and the end of each intervention. Metabolite markers of appetite were measured pre and post intervention in fasting plasma. Results: 31 adults (63 ± 13 years old, BMI 32.4 ± 7, HbA1c 7.5 ± 3.4% (59 ± 14 mmol mol-1)) commenced the trial, 28 (90%) completed both interventions. Wholegrain consumption, as measured by alkylresorcinols, was balanced between interventions. Self-reported pre-meal hunger was consistently lower at breakfast (MD, mean difference 0.49/10 95% CI 0.03 to 0.94), lunch (MD 0.67/10 95% CI 0.09 to 1.25), and dinner (MD -0.71/10 95% CI 0.19 to 1.23) during the intervention of less processed whole grains when compared with pre-intervention measures, however this did not result in a difference between interventions. Change in metabolite markers of appetite did not differ between interventions. Conclusions: A significant difference in hunger or satiety between less and more processed whole grains over intervention periods of two weeks was not detected within the current trial. Further experimental studies are needed to consider the potential effects of food processing on physiological processes such as appetite to provide mechanistic understanding behind observations of highly processed food intakes and adverse health outcomes.

Proton pump inhibitor use: systematic review of global trends and practices.

PURPOSE: Proton pump inhibitors (PPIs) reduce acid secretion in the stomach and rank as one of the most widely used acid-suppressing medicines globally. While PPIs are safe in the short-term, emerging evidence shows risks associated with long-term use. Current evidence on global PPI use is scarce. This systematic review aims to evaluate global PPI use in the general population. METHODS: Ovid MEDLINE, Embase, and International Pharmaceutical Abstracts were systematically searched from inception to 31 March 2023 to identify observational studies on oral PPI use among individuals aged ≥ 18 years. PPI use was classified by demographics and medication factors (dose, duration, and PPI types). The absolute numbers of PPI users for each subcategory were summed and expressed as a percentage. RESULTS: The search identified data from 28 million PPI users in 23 countries from 65 articles. This review indicated that nearly one-quarter of adults use a PPI. Of those using PPIs, 63% were less than 65 years. 56% of PPI users were female, and "White" ethnicities accounted for 75% of users. Nearly two-thirds of users were on high doses (≥ defined daily dose (DDD)), 25% of users continued PPIs for > 1 year, and 28% of these continued for > 3 years. CONCLUSION: Given the widespread use PPIs and increasing concern regarding long-term use, this review provides a catalyst to support more rational use, particularly with unnecessary prolonged continuation. Clinicians should review PPI prescriptions regularly and deprescribe when there is no appropriate ongoing indication or evidence of benefit to reduce health harm and treatment cost.

Synthesising Programs with Non-trivial Constants.

Program synthesis is the mechanised construction of software. One of the main difficulties is the efficient exploration of the very large solution space, and tools often require a user-provided syntactic restriction of the search space. While useful in general, such syntactic restrictions provide little help for the generation of programs that contain non-trivial constants, unless the user is able to provide the constants in advance. This is a fundamentally difficult task for state-of-the-art synthesisers. We propose a new approach to the synthesis of programs with non-trivial constants that combines the strengths of a counterexample-guided inductive synthesiser with those of a theory solver, exploring the solution space more efficiently without relying on user guidance. We call this approach CEGIS(T), where T is a first-order theory. We present two exemplars, one based on Fourier-Motzkin (FM) variable elimination and one based on first-order satisfiability. We demonstrate the practical value of CEGIS(T) by automatically synthesising programs for a set of intricate benchmarks. Additionally, we present a case study where we integrate CEGIS(T) within the mature synthesiser CVC4 and show that CEGIS(T) improves CVC4's results.

A View on Drug Development for Cancer Prevention.

Despite some notable successes, there are still relatively few agents approved for cancer prevention. Here we review progress thus far in the development of medicines for cancer prevention, and we outline some key concepts that could further enable or accelerate drug development for cancer prevention in the future. These are summarized under six key themes: (i) unmet clinical need, (ii) patient identification, (iii) risk stratification, (iv) pharmacological intervention, (v) clinical trials, and (vi) health care policy. These concepts, if successfully realized, may help to increase the number of medicines available for cancer prevention. SIGNIFICANCE: The huge potential public health benefits of preventing cancer, combined with recent advances in the availability of novel early detection technologies and new treatment modalities, has caused us to revisit the opportunities and challenges associated with developing medicines to prevent cancer. Here we review progress in the field of developing medicines to prevent cancer to date, and we present a series of ideas that might help in the development of more medicines to prevent cancer in the future.

C3a-C3aR signaling is a novel modulator of skeletal homeostasis.

Osteoimmune studies have identified complement signaling as an important regulator of the skeleton. Specifically, complement anaphylatoxin receptors (i.e., C3aR, C5aR) are expressed on osteoblasts and osteoclasts, implying that C3a and/or C5a may be candidate mediators of skeletal homeostasis. The study aimed to determine how complement signaling influences bone modeling/remodeling in the young skeleton. Female C57BL/6J C3aR-/-C5aR-/- vs. wildtype and C3aR-/- vs. wildtype mice were examined at age 10 weeks. Trabecular and cortical bone parameters were analyzed by micro-CT. In situ osteoblast and osteoclast outcomes were determined by histomorphometry. Osteoblast and osteoclast precursors were assessed in vitro. C3aR-/-C5aR-/- mice displayed an increased trabecular bone phenotype at age 10 weeks. In vitro studies revealed C3aR-/-C5aR-/- vs. wildtype cultures had less bone-resorbing osteoclasts and increased bone-forming osteoblasts, which were validated in vivo. To determine whether C3aR alone was critical for the enhanced skeletal outcomes, wildtype vs. C3aR-/- mice were evaluated for osseous tissue outcomes. Paralleling skeletal findings in C3aR-/-C5aR-/- mice, C3aR-/- vs. wildtype mice had an enhanced trabecular bone volume fraction, which was attributed to increased trabecular number. There was elevated osteoblast activity and suppressed osteoclastic cells in C3aR-/- vs. wildtype mice. Furthermore, primary osteoblasts derived from wildtype mice were stimulated with exogenous C3a, which more profoundly upregulated C3ar1 and the pro-osteoclastic chemokine Cxcl1. This study introduces the C3a/C3aR signaling axis as a novel regulator of the young skeleton.

Heritable Risk and Protective Genetic Components of Glaucoma Medication Non-Adherence.

Glaucoma is the leading cause of irreversible blindness, affecting 76 million globally. It is characterized by irreversible damage to the optic nerve. Pharmacotherapy manages intraocular pressure (IOP) and slows disease progression. However, non-adherence to glaucoma medications remains problematic, with 41-71% of patients being non-adherent to their prescribed medication. Despite substantial investment in research, clinical effort, and patient education protocols, non-adherence remains high. Therefore, we aimed to determine if there is a substantive genetic component behind patients' glaucoma medication non-adherence. We assessed glaucoma medication non-adherence with prescription refill data from the Marshfield Clinic Healthcare System's pharmacy dispensing database. Two standard measures were calculated: the medication possession ratio (MPR) and the proportion of days covered (PDC). Non-adherence on each metric was defined as less than 80% medication coverage over 12 months. Genotyping was done using the Illumina HumanCoreExome BeadChip in addition to exome sequencing on the 230 patients (1) to calculate the heritability of glaucoma medication non-adherence and (2) to identify SNPs and/or coding variants in genes associated with medication non-adherence. Ingenuity pathway analysis (IPA) was utilized to derive biological meaning from any significant genes in aggregate. Over 12 months, 59% of patients were found to be non-adherent as measured by the MPR80, and 67% were non-adherent as measured by the PDC80. Genome-wide complex trait analysis (GCTA) suggested that 57% (MPR80) and 48% (PDC80) of glaucoma medication non-adherence could be attributed to a genetic component. Missense mutations in TTC28, KIAA1731, ADAMTS5, OR2W3, OR10A6, SAXO2, KCTD18, CHCHD6, and UPK1A were all found to be significantly associated with glaucoma medication non-adherence by whole exome sequencing after Bonferroni correction (p < 10-3) (PDC80). While missense mutations in TINAG, CHCHD6, GSTZ1, and SEMA4G were found to be significantly associated with medication non-adherence by whole exome sequencing after Bonferroni correction (p < 10-3) (MPR80). The same coding SNP in CHCHD6 which functions in Alzheimer's disease pathophysiology was significant by both measures and increased risk for glaucoma medication non-adherence by three-fold (95% CI, 1.62-5.8). Although our study was underpowered for genome-wide significance, SNP rs6474264 within ZMAT4 (p = 5.54 × 10-6) was found to be nominally significant, with a decreased risk for glaucoma medication non-adherence (OR, 0.22; 95% CI, 0.11-0.42)). IPA demonstrated significant overlap, utilizing, both standard measures including opioid signaling, drug metabolism, and synaptogenesis signaling. CREB signaling in neurons (which is associated with enhancing the baseline firing rate for the formation of long-term potentiation in nerve fibers) was shown to have protective associations. Our results suggest a substantial heritable genetic component to glaucoma medication non-adherence (47-58%). This finding is in line with genetic studies of other conditions with a psychiatric component (e.g., post-traumatic stress disorder (PTSD) or alcohol dependence). Our findings suggest both risk and protective statistically significant genes/pathways underlying glaucoma medication non-adherence for the first time. Further studies investigating more diverse populations with larger sample sizes are needed to validate these findings.