Lawesson's Reagent: Providing a New Approach to the Forgotten 6-Thioverdazyl Radical.

A new method for the preparation of the underrepresented 1,5-dimethyl-6-thioverdazyl radicals has been developed employing Lawesson's reagent (LR). The synthetic route involves the direct thionation of the carbonyl group of the corresponding dialkylbishydrazone followed by cyclization to give the tetrazinanthione verdazyl precursor on a gram scale. Subsequent oxidation yields the 6-thioverdazyl radical. It was determined that thionation of substrates containing electron-withdrawing groups in the ortho- or para-positions was high yielding. In contrast, for the parent phenyl group or substrates bearing weakly electron-donating substituents, thionation efficiency was significantly reduced. This could be overcome by utilizing partial in situ cyclization, which occurs during work up, to generate the tetrazinanthione directly via a one-pot synthesis. Density functional theory suggests that the LR fragment interacts with the carbonyl prior to cycloaddition and subsequent to cycloreversion, leading to the thiocarbonyl. The electronic nature of the radical is characterized with electron paramagnetic resonance as well as the first report of 6-thioverdazyl redox properties.

Behavioural activation to mitigate the psychological impacts of COVID-19 restrictions on older people in England and Wales (BASIL+): a pragmatic randomised controlled trial.

BACKGROUND: Older adults were more likely to be socially isolated during the COVID-19 pandemic, with increased risk of depression and loneliness. We aimed to investigate whether a behavioural activation intervention delivered via telephone could mitigate depression and loneliness in at-risk older people during the COVID-19 pandemic. METHODS: BASIL+ (Behavioural Activation in Social Isolation) was a pragmatic randomised controlled trial conducted among patients recruited from general practices in England and Wales, and was designed to assess the effectiveness of behavioural activation in mitigating depression and loneliness among older people during the COVID-19 pandemic. Eligible participants were aged 65 years and older, socially isolated, with a score of 5 or higher on the Patient Health Questionnaire-9 (PHQ-9), and had multiple long-term conditions. Participants were allocated in a 1:1 ratio to the intervention (behavioural activation) or control groups by use of simple randomisation without stratification. Behavioural activation was delivered by telephone; participants were offered up to eight weekly sessions with trained BASIL+ Support Workers. Behavioural activation was adapted to maintain social connections and encourage socially reinforcing activities. Participants in the control group received usual care with existing COVID-19 wellbeing resources. The primary clinical outcome was self-reported depression severity, assessed by the PHQ-9, at 3 months. Outcomes were assessed masked to allocation and analysis was by treatment allocation. This trial is registered with the ISRCTN registry (ISRCTN63034289). FINDINGS: Between Feb 8, 2021, and Feb 28, 2022, 449 eligible participants were identified and 435 from 26 general practices were recruited and randomly assigned (1:1) to the behavioural activation intervention (n=218) or to the control group (usual care with signposting; n=217). The mean age of participants was 75·7 years (SD 6·7); 270 (62·1%) of 435 participants were female, and 418 (96·1%) were White. Participants in the intervention group attended an average of 5·2 (SD 2·9) of eight remote behavioural activation sessions. The adjusted mean difference in PHQ-9 scores between the control and intervention groups at 3 months was -1·65 (95% CI -2·54 to -0·75, p=0·0003). No adverse events were reported that were attributable to the behavioural activation intervention. INTERPRETATION: Behavioural activation is an effective and potentially scalable intervention that can reduce symptoms of depression and emotional loneliness in at-risk groups in the short term. The findings of this trial add to the range of strategies to improve the mental health of older adults with multiple long-term conditions. These results can be helpful to policy makers beyond the pandemic in reducing the global burden of depression and addressing the health impacts of loneliness, particularly in at-risk groups. FUNDING: UK National Institute for Health and Care Research.

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.

Factors associated with low fruit and vegetable consumption among people with severe mental ill health.

Severe mental ill health (SMI) is associated with excess mortality, and poor diet is one associated modifiable risk factor. This study investigated factors associated with low consumption of fruit and vegetables among people with SMI (N = 9914). A total of 8.4% of participants ate no portions per day, while only 15% ate 5 + portions. Individuals who never consumed fruit and vegetables or ate < 5 portions per day were more likely to be male, younger than 65, unemployed, experience poorer general health, or perceive health as unimportant. Poor diet is common among people with SMI and tailored dietary improvement interventions are required.

Diagnosis, management, and outcome of an intralenticular foreign body in a dog: A case report.

Background: Intra-lenticular foreign bodies are rare in veterinary medicine and uncommon in human medicine. Approximately 50% of perforating ocular injuries in canines have lenticular involvement. Treatment choices include conservative management and surgical options. Retained intra-lenticular foreign body with delayed removal has not been reported in animals. Case Description: A 3-year-old male neutered Lurcher presented with right-sided ocular discomfort and a sealed full-thickness corneal perforation. The full ophthalmic examination could not be performed at the initial presentation due to miosis. Recrudescence of anterior uveitis was seen post-drug cessation. Re-evaluation of the eye with a mydriatic pupil revealed an intra-lenticular foreign body. Surgical removal via phacoemulsification was performed 8 weeks after the initial perforating injury. The eye remains visual, comfortable, and normotensive 50 months post-operatively. Conclusion: This is the first report of an encapsulated, retained intra-lenticular foreign body with delayed removal in a dog. Mydriasis and repeat examinations are of crucial importance when evaluating eyes post-perforation.

Tandem High-Pressure Crystallography-Optical Spectroscopy Unpacks Noncovalent Interactions of Piezochromic Fluorescent Molecular Rotors.

To develop luminescent molecular materials with predictable and stimuli-responsive emission, it is necessary to correlate changes in their geometries, packing structures, and noncovalent interactions with the associated changes in their optical properties. Here, we demonstrate that high-pressure single-crystal X-ray diffraction can be combined with high-pressure UV-visible absorption and fluorescence emission spectroscopies to elucidate how subtle changes in structure influence optical outputs. A piezochromic aggregation-induced emitter, sym-heptaphenylcycloheptatriene (Ph7C7H), displays bathochromic shifts in its absorption and emission spectra at high pressure. Parallel X-ray measurements identify the pressure-induced changes in specific phenyl-phenyl interactions responsible for the piezochromism. Pairs of phenyl rings from neighboring molecules approach the geometry of a stable benzene dimer, while conformational changes alter intramolecular phenyl-phenyl interactions correlated with a relaxed excited state. This tandem crystallographic and spectroscopic analysis provides insights into how subtle structural changes relate to the photophysical properties of Ph7C7H and could be applied to a library of similar compounds to provide general structure-property relationships in fluorescent organic molecules with rotor-like geometries.

Statistical agreement of gonioscopy performed as a puppy and as an adult in the Samoyed dog.

OBJECTIVE: To assess whether gonioscopy performed on Samoyed puppies (6-14 weeks of age) is a reliable predictor of their gonioscopy results as adults (>11 months of age). PROCEDURE: A retrospective medical record search was performed to identify Samoyed dogs that had undergone gonioscopy as a puppy (6-14 weeks of age). A second prospective gonioscopy examination was performed as an adult (>11 months of age) and the results were compared. Gonioscopy was assessed on two characteristics: percent of iridocorneal angle (ICA) unaffected by pectinate ligament abnormalities (PLA) and ICA width, with PLA results categorized into unaffected ( ≥ $$ \ge $$ 75% open), moderately affected (50%-74% open), and severely affected (<50% open) and the width categorized into wide, moderate, narrow, and closed groups. A multivariate model was created that considered factors such as PLA, angle width, sex, puppy age, neuter status, and time between examinations. RESULTS: The eyes of 77 Samoyed dogs (154 eyes) met inclusion criteria. When assessing PLA, 90% of dogs had the same categorization as a puppy and as an adult. When assessing ICA width, 53.2% of dogs had the same width classification as a puppy and as an adult. There is strong evidence that variation between puppy and adult results increases with time between examination (p = .03). CONCLUSION: Puppies unaffected by PLA and with a wide ICA angle, are likely to retain these features as adults. Selection of puppies with desirable gonioscopic traits may help breeders to choose dogs likely to retain these traits as adults for breeding. This may reduce the incidence of glaucoma in the breed. Puppy examinations should be performed in both eyes. Examination of adults prior to breeding remains prudent.

Pressure-induced postsynthetic cluster anion substitution in a MIL-53 topology scandium metal-organic framework.

Postsynthetic modification of metal-organic frameworks (MOFs) has proven to be a hugely powerful tool to tune physical properties and introduce functionality, by exploiting reactive sites on both the MOF linkers and their inorganic secondary building units (SBUs), and so has facilitated a wide range of applications. Studies into the reactivity of MOF SBUs have focussed solely on removal of neutral coordinating solvents, or direct exchange of linkers such as carboxylates, despite the prevalence of ancillary charge-balancing oxide and hydroxide ligands found in many SBUs. Herein, we show that the µ2-OH ligands in the MIL-53 topology Sc MOF, GUF-1, are labile, and can be substituted for µ2-OCH3 units through reaction with pore-bound methanol molecules in a very rare example of pressure-induced postsynthetic modification. Using comprehensive solid-state NMR spectroscopic analysis, we show an order of magnitude increase in this cluster anion substitution process after exposing bulk samples suspended in methanol to a pressure of 0.8 GPa in a large volume press. Additionally, single crystals compressed in diamond anvil cells with methanol as the pressure-transmitting medium have enabled full structural characterisation of the process across a range of pressures, leading to a quantitative single-crystal to single-crystal conversion at 4.98 GPa. This unexpected SBU reactivity - in this case chemisorption of methanol - has implications across a range of MOF chemistry, from activation of small molecules for heterogeneous catalysis to chemical stability, and we expect cluster anion substitution to be developed into a highly convenient novel method for modifying the internal pore surface and chemistry of a range of porous materials.

High-pressure single-crystal diffraction at the Australian Synchrotron.

A new high-pressure single-crystal diffraction setup has been designed and implemented at the Australian Synchrotron for collecting molecular and protein crystal structures. The setup incorporates a modified micro-Merrill-Bassett cell and holder designed specifically to fit onto the horizontal air-bearing goniometer, allowing high-pressure diffraction measurements to be collected with little to no modification of the beamline setup compared with ambient data collections. Compression data for the amino acid, L-threonine, and the protein, hen egg-white lysozyme, were collected, showcasing the capabilities of the setup.

Improving programme-led and focused interventions for eating disorders: An experts' consensus statement-A UK perspective.

OBJECTIVE: Eating disorders are associated with significant illness burden and costs, yet access to evidence-based care is limited. Greater use of programme-led and focused interventions that are less resource-intensive might be part of the solution to this demand-capacity mismatch. METHOD: In October 2022, a group of predominantly UK-based clinical and academic researchers, charity representatives and people with lived experience convened to consider ways to improve access to, and efficacy of, programme-led and focused interventions for eating disorders in an attempt to bridge the demand-capacity gap. RESULTS: Several key recommendations were made across areas of research, policy, and practice. Of particular importance is the view that programme-led and focused interventions are suitable for a range of different eating disorder presentations across all ages, providing medical and psychiatric risk are closely monitored. The terminology used for these interventions should be carefully considered, so as not to imply that the treatment is suboptimal. CONCLUSIONS: Programme-led and focused interventions are a viable option to close the demand-capacity gap for eating disorder treatment and are particularly needed for children and young people. Work is urgently needed across sectors to evaluate and implement such interventions as a clinical and research priority.

Adapting an online guided self-help intervention for the management of binge eating in adults with type 2 diabetes: The POSE-D study.

AIMS: People with type 2 diabetes (T2D) are more likely to experience binge eating than the general population, which may interfere with their diabetes management. Guided self-help (GSH) is the recommended treatment for binge-eating disorder, but there is currently a lack of evidenced treatment for binge eating in individuals living with T2D. The aims of the current study were to adapt an existing evidence-based GSH intervention using the principles of co-design to make it available online, suitable for remote delivery to address binge eating specifically in adults living with T2D. The Working to Overcome Eating Difficulties GSH intervention comprises online GSH materials presented in seven sections delivered over 12 weeks, supported by a trained Guide. METHODS: In order to adapt the intervention, we held four collaboration workshops with three expert patients recruited from diabetes support groups, eight healthcare professionals and an expert consensus group. We used thematic analysis to make sense of the data. RESULTS AND CONCLUSIONS: The main themes included; keeping the GSH material generic, adapting Sam the central character, tailoring the dietary advice and eating diary. The length of Guidance sessions was increased to 60 min, and Guide training was focussed around working with people with diabetes.

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.

Emotional Eating Interventions for Adults Living with Overweight or Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Emotional eating (EE) may be defined as a tendency to eat in response to negative emotions and energy-dense and palatable foods, and is common amongst adults with overweight or obesity. There is limited evidence regarding the effectiveness of interventions that address EE. OBJECTIVES: To synthesize evidence on the effectiveness of EE interventions for weight loss and EE in adults living with overweight or obesity. METHODS: This is a systematic review and meta-analysis. Adhering to the PRISMA guidance, a comprehensive electronic search was completed up to February 2022. Random effects meta-analysis was carried out to determine the percentage change in weight and EE scores. RESULTS: Thirty-four studies were included. The combined effect size for percentage weight change was -1.08% (95% CI: -1.66 to -0.49, I2 = 64.65%, n = 37), once adjusted for publication bias. Similarly, the combined effect size for percentage change in EE was -2.37%, (95% CI: -3.76 to -0.99, I2 = 87.77%, n = 46). Cognitive Behavioural Therapy showed the most promise for reducing weight and improving EE. CONCLUSIONS: Interventions to address EE showed promise in reducing EE and promoted a small amount of weight loss in adults living with overweight or obesity.

Impact of glycaemic technologies on quality of life and related outcomes in adults with type 1 diabetes: A narrative review.

AIMS: To explore the association between the use of glycaemic technologies and person-reported outcomes (PROs) in adults with type 1 diabetes (T1D). METHODS: We included T1D and technology publications reporting on PROs since 2014. Only randomised controlled trials and cohort studies that used validated PRO measures (PROMs) were considered. RESULTS: T1D studies reported on a broad range of validated PROMs, mainly as secondary outcome measures. Most studies examined continuous glucose monitoring (CGM), intermittently scanned CGM (isCGM), and the role of continuous subcutaneous insulin infusion (CSII), including sensor-augmented CSII and closed loop systems. Generally, studies demonstrated a positive impact of technology on hypoglycaemia-specific and diabetes-specific PROs, including reduced fear of hypoglycaemia and diabetes distress, and greater satisfaction with diabetes treatment. In contrast, generic PROMs (including measures of health/functional status, emotional well-being, depressive symptoms, and sleep quality) were less likely to demonstrate improvements associated with the use of glycaemic technologies. Several studies showed contradictory findings, which may relate to study design, population and length of follow-up. Differences in PRO findings were apparent between randomised controlled trials and cohort studies, which may be due to different populations studied and/or disparity between trial and real-world conditions. CONCLUSIONS: PROs are usually assessed as secondary outcomes in glycaemic technology studies. Hypoglycaemia-specific and diabetes-specific, but not generic, PROs show the benefits of glycaemic technologies, and deserve a more central role in future studies as well as routine clinical care.

Can we mitigate the psychological impacts of social isolation using behavioural activation? Long-term results of the UK BASIL urgent public health COVID-19 pilot randomised controlled trial and living systematic review.

BACKGROUND: Behavioural and cognitive interventions remain credible approaches in addressing loneliness and depression. There was a need to rapidly generate and assimilate trial-based data during COVID-19. OBJECTIVES: We undertook a parallel pilot RCT of behavioural activation (a brief behavioural intervention) for depression and loneliness (Behavioural Activation in Social Isolation, the BASIL-C19 trial ISRCTN94091479). We also assimilate these data in a living systematic review (PROSPERO CRD42021298788) of cognitive and/or behavioural interventions. METHODS: Participants (≥65 years) with long-term conditions were computer randomised to behavioural activation (n=47) versus care as usual (n=49). Primary outcome was PHQ-9. Secondary outcomes included loneliness (De Jong Scale). Data from the BASIL-C19 trial were included in a metanalysis of depression and loneliness. FINDINGS: The 12 months adjusted mean difference for PHQ-9 was -0.70 (95% CI -2.61 to 1.20) and for loneliness was -0.39 (95% CI -1.43 to 0.65).The BASIL-C19 living systematic review (12 trials) found short-term reductions in depression (standardised mean difference (SMD)=-0.31, 95% CI -0.51 to -0.11) and loneliness (SMD=-0.48, 95% CI -0.70 to -0.27). There were few long-term trials, but there was evidence of some benefit (loneliness SMD=-0.20, 95% CI -0.40 to -0.01; depression SMD=-0.20, 95% CI -0.47 to 0.07). DISCUSSION: We delivered a pilot trial of a behavioural intervention targeting loneliness and depression; achieving long-term follow-up. Living meta-analysis provides strong evidence of short-term benefit for loneliness and depression for cognitive and/or behavioural approaches. A fully powered BASIL trial is underway. CLINICAL IMPLICATIONS: Scalable behavioural and cognitive approaches should be considered as population-level strategies for depression and loneliness on the basis of a living systematic review.

Pressure and guest-mediated pore shape modification in a small pore MOF to 1200 bar.

Guest-mediated pore-shape modification of the metal-organic framework, Sc2BDC3 upon adsorption of n-pentane and isopentane is examined from 50-1200 bar. Rotation of the BDC linker responsible for the change in pore shape occurs at much lower pressures than previously reported, with distinct adsorption behaviour observed between pentane isomers.

Regulation of Multistep Spin Crossover Across Multiple Stimuli in a 2-D Framework Material.

We investigate the effects of a broad array of external stimuli on the structural, spin-crossover (SCO) properties and nature of the elastic interaction within the two-dimensional Hofmann framework material [Fe(cintrz)2Pd(CN)4]·guest (cintrz = N-cinnamalidene 4-amino-1,2,4-triazole; A·guest; guest = 3H2O, 2H2O, and Ø). This framework exhibits a delicate balance between ferro- and antiferro-elastic interaction characters; we show that manipulation of the pore contents across guests = 3H2O, 2H2O, and Ø can be exploited to regulate this balance. In A·3H2O, the dominant antiferroelastic interaction character between neighboring FeII sites sees the low-temperature persistence of the mixed spin-state species {HS-LS} for {Fe1-Fe2} (HS = high spin, LS = low spin). Elastic interaction strain is responsible for stabilizing the {HS-LS} state and can be overcome by three mechanisms: (1) partial (2H2O) or complete (Ø) guest removal, (2) irradiation via the reverse light-induced excited spin-state trapping (LIESST) effect (λ = 830 nm), and (3) the application of external hydrostatic pressure. Combining experimental data with elastic models presents a clear interpretation that while guest molecules cause a negative chemical pressure, they also have consequences for the elastic interactions between metals beyond the simple chemical pressure picture typically proposed.

Behavioural Activation for Social IsoLation (BASIL+) trial (Behavioural activation to mitigate depression and loneliness among older people with long-term conditions): Protocol for a fully-powered pragmatic randomised controlled trial.

INTRODUCTION: Depression is a leading mental health problem worldwide. People with long-term conditions are at increased risk of experiencing depression. The COVID-19 pandemic led to strict social restrictions being imposed across the UK population. Social isolation can have negative consequences on the physical and mental wellbeing of older adults. In the Behavioural Activation in Social IsoLation (BASIL+) trial we will test whether a brief psychological intervention (based on Behavioural Activation), delivered remotely, can mitigate depression and loneliness in older adults with long-term conditions during isolation. METHODS: We will conduct a two-arm, parallel-group, randomised controlled trial across several research sites, to evaluate the clinical and cost-effectiveness of the BASIL+ intervention. Participants will be recruited via participating general practices across England and Wales. Participants must be aged ≥65 with two or more long-term conditions, or a condition that may indicate they are within a 'clinically extremely vulnerable' group in relation to COVID-19, and have scored ≥5 on the Patient Health Questionnaire (PHQ9), to be eligible for inclusion. Randomisation will be 1:1, stratified by research site. Intervention participants will receive up to eight intervention sessions delivered remotely by trained BASIL+ Support Workers and supported by a self-help booklet. Control participants will receive usual care, with additional signposting to reputable sources of self-help and information, including advice on keeping mentally and physically well. A qualitative process evaluation will also be undertaken to explore the acceptability of the BASIL+ intervention, as well as barriers and enablers to integrating the intervention into participants' existing health and care support, and the impact of the intervention on participants' mood and general wellbeing in the context of the COVID-19 restrictions. Semi-structured interviews will be conducted with intervention participants, participant's caregivers/supportive others and BASIL+ Support Workers. Outcome data will be collected at one, three, and 12 months post-randomisation. Clinical and cost-effectiveness will be evaluated. The primary outcome is depressive symptoms at the three-month follow up, measured by the PHQ9. Secondary outcomes include loneliness, social isolation, anxiety, quality of life, and a bespoke health services use questionnaire. DISCUSSION: This study is the first large-scale trial evaluating a brief Behavioural Activation intervention in this population, and builds upon the results of a successful external pilot trial. TRIAL REGISTRATION: ClinicalTrials.Gov identifier ISRCTN63034289, registered on 5th February 2021.

Clinical outcome of intravitreal gentamicin injection for the treatment of end-stage glaucoma in five rabbits (eight eyes).

Background: Glaucoma is a painful and blinding condition that occurs in many species, including rabbits. When medication is no longer effective in maintaining intraocular pressure (IOP), enucleation is the recognized treatment for rabbits with end-stage glaucoma. However, this procedure carries risks relating to the procedure and the anesthesia. Aim: The aim of this retrospective study was to report the efficacy of intravitreal gentamicin injection in controlling IOP in blind eyes of rabbits with end-stage glaucoma. Ocular and non-ocular complications were retrospectively assessed. Methods: Medical record review was performed to identify five client-owned rabbits (eight eyes) that were treated by intravitreal injection of 6-20 mg of gentamicin per eye (median 7.18 mg/kg) for chronic, end-stage glaucoma. Treatment was unilateral in two and bilateral in three rabbits. IOP control was assessed via rebound tonometry readings performed approximately 2 weeks, 1 month, 3 months, and 6 months after injection. Total follow-up was between 313 and 1,111 days. Ocular complications were recorded and systemic health was estimated by the owner-answered questionnaire and changes in body weight. Results: IOP was <25 mmHg in 87.5% of eyes 3 months post-injection. The most common ocular complications were cataracts (62.5%), anterior uveitis (25%), retinal detachment (12.5%), and corneal erosion (12.5%). There were no behavioral or body weight changes suggestive of systemic complications. Conclusion: 87.5% of rabbit eyes treated with intravitreal gentamicin had controlled IOP 3 months after injection. All eyes were blind at the time of injection. Ocular side effects were common. Investigation of the safety and systemic effects of intravitreal gentamicin injection is required; however, no overt complications were identified in treated rabbits in this study.

Enhanced synthesis of oxo-verdazyl radicals bearing sterically-and electronically-diverse C3-substituents.

The synthetic viability of the hydrazine- and phosgene-free synthesis of 1,5-dimethyl oxo-verdazyl radicals has been improved via a detailed study investigating the influence of the aryl substituent on tetrazinanone ring formation. Although it is well established that functionalisation at the C3 position of the tetrazinanone ring does not influence the nature of the radical, it is crucial in applications development. The synthetic route involves a 4-step sequence: Schiff base condensation of a carbohydrazide with an arylaldehyde, alkylation, ring closure then subsequent oxidation to the radical. We found that the presence of strong electron-donating substituents and electron rich heterocycles, result in a significant reduction in yield during both the alkylation and ring closure steps. This can, in part, be alleviated by milder alkylation conditions and further substitution of the aryl group. In comparison, more facile formation of the tetrazine ring was observed with examples containing electron-withdrawing groups and with meta- or para-substitution. Density functional theory suggests that the ring closure proceeds via the formation of an ion pair. Electron paramagnetic resonance spectroscopy provides insight into the precise electronic structure of the radical with small variations in hyperfine coupling constants revealing subtle differences.