Multicentre service evaluation of injectable cabotegravir and rilpivirine delivery and outcomes across 12 UK clinics (SHARE LAI-net).

INTRODUCTION: Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics. METHODS: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia. RESULTS: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV. CONCLUSION: In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure.

Pseudohypoaldosteronism and acquired renal aldosterone resistance with hyperkalemic type IV renal tubular acidosis in 2 cats.

This report describes the diagnosis and treatment of aldosterone resistance (AR) and acquired hyperkalemic type IV renal tubular acidosis (RTA) in 2 cats comparable to acquired pseudohypoaldosteronism in people. One cat developed AR from chronic kidney disease after an acute kidney injury and was treated with furosemide per os, which resolved the hyperkalemic RTA. The second cat developed transient AR secondary to a bacterial urinary tract infection associated with urethral catheterization, and treatment with antibiotics resolved the hyperkalemic RTA.

Modulated Self-Assembly of Catalytically Active Metal-Organic Nanosheets Containing Zr6 Clusters and Dicarboxylate Ligands.

Two-dimensional metal-organic nanosheets (MONs) have emerged as attractive alternatives to their three-dimensional metal-organic framework (MOF) counterparts for heterogeneous catalysis due to their greater external surface areas and higher accessibility of catalytically active sites. Zr MONs are particularly prized because of their chemical stability and high Lewis and Brønsted acidities of the Zr clusters. Herein, we show that careful control over modulated self-assembly and exfoliation conditions allows the isolation of the first example of a two-dimensional nanosheet wherein Zr6 clusters are linked by dicarboxylate ligands. The hxl topology MOF, termed GUF-14 (GUF = Glasgow University Framework), can be exfoliated into monolayer thickness hns topology MONs, and acid-induced removal of capping modulator units yields MONs with enhanced catalytic activity toward the formation of imines and the hydrolysis of an organophosphate nerve agent mimic. The discovery of GUF-14 serves as a valuable example of the undiscovered MOF/MON structural diversity extant in established metal-ligand systems that can be accessed by harnessing the power of modulated self-assembly protocols.

International renal interest society best practice consensus guidelines for intermittent hemodialysis in dogs and cats.

Intermittent hemodialysis (IHD) is an advanced adjunctive standard of care for severe acute kidney injury (AKI) and other indications. Most animals with AKI are managed medically, however, when the disease is severe, medical management may not control the consequences of the disease, and animals with a potential for renal recovery may die from the consequences of uremia before recovery has occurred. Extracorporeal therapies aid the management of AKI by expanding the window of opportunity for recovery of sufficient kidney function to become dialysis independent. Intermittent hemodialysis (IHD) was introduced into veterinary medicine over 50 years ago, however, updated guidelines for the delivery of IHD have not been published for several decades. To that end, the International Renal Interest Society (IRIS) constituted a Working Group to establish best practice guidelines for the safe and effective delivery of IHD to animals with indications for dialytic intervention. The IRIS Working Group generated 60 consensus statements and supporting rational for a spectrum of prescription and management categories required for delivery of IHD on designated intermittent dialysis platforms (i.e., AKI, chronic hemodialysis and intoxications). A formal consensus method was used to validate the recommendations by a blinded jury of 12 veterinarians considered experts in extracorporeal therapies and actively performing IHD. Each vote provided a level of agreement for each recommendation proposed by the Working Group. To achieve a consensus, a minimum of 75% of the voting participants had to "strongly agree" or "agree" with the recommendation.

Exploring young people's attitudes to HIV prevention medication (PrEP) in England: a qualitative study.

INTRODUCTION: Young people aged 18-24 years old are a key demographic target for eliminating HIV transmission globally. Pre-exposure prophylaxis (PrEP), a prevention medication, reduces HIV transmission. Despite good uptake by gay and bisexual men who have sex with men, hesitancy to use PrEP has been observed in other groups, such as young people and people from ethnic minority backgrounds. The aim of this study was to explore young people's perceptions and attitudes to using PrEP. DESIGN: A qualitative transcendental phenomenological design was used. PARTICIPANTS AND SETTING: A convenience sample of 24 young people aged between 18 and 24 years was recruited from England. METHODS: Semistructured interviews and graphical elicitation were used to collect data including questions about current experiences of HIV care, awareness of using PrEP and decision-making about accessing PrEP. Thematic and visual analyses were used to identify findings. RESULTS: Young people had good levels of knowledge about HIV but poor understanding of using PrEP. In this information vacuum, negative stigma and stereotypes about HIV and homosexuality were transferred to using PrEP, which were reinforced by cultural norms portrayed on social media, television and film-such as an association between using PrEP and being a promiscuous, white, gay male. In addition, young people from ethnic minority communities appeared to have negative attitudes to PrEP use, compared with ethnic majority counterparts. This meant these young people in our study were unable to make decisions about when and how to use PrEP. CONCLUSION: Findings indicate an information vacuum for young people regarding PrEP. A strength of the study is that theoretical data saturation was reached. A limitation of the study is participants were largely from Northern England, which has low prevalence of HIV. Further work is required to explore the information needs of young people in relation to PrEP.

International Renal Interest Society best practice consensus guidelines for the diagnosis and management of acute kidney injury in cats and dogs.

Acute kidney injury (AKI) is defined as an injury to the renal parenchyma, with or without a decrease in kidney function, as reflected by accumulation of uremic toxins or altered urine production (i.e., increased or decreased). AKI might result from any of several factors, including ischemia, inflammation, nephrotoxins, and infectious diseases. AKI can be community- or hospital-acquired. The latter was not previously considered a common cause for AKI in animals; however, recent evidence suggests that the prevalence of hospital-acquired AKI is increasing in veterinary medicine. This is likely due to a combination of increased recognition and awareness of AKI, as well as increased treatment intensity (e.g., ventilation and prolonged hospitalization) in some veterinary patients and increased management of geriatric veterinary patients with multiple comorbidities. Advancements in the management of AKI, including the increased availability of renal replacement therapies, have been made; however, the overall mortality of animals with AKI remains high. Despite the high prevalence of AKI and the high mortality rate, the body of evidence regarding the diagnosis and the management of AKI in veterinary medicine is very limited. Consequently, the International Renal Interest Society (IRIS) constructed a working group to provide guidelines for animals with AKI. Recommendations are based on the available literature and the clinical experience of the members of the working group and reflect consensus of opinion. Fifty statements were generated and were voted on in all aspects of AKI and explanatory text can be found either before or after each statement.

ACVIM consensus statement on diagnosis and management of urinary incontinence in dogs.

Urinary incontinence (UI) is a disorder of micturition that can occur in dogs of any age, sex, and breed depending on the underlying cause and time of onset. Diagnosis and treatment for various causes of UI in dogs have been described by multiple comprehensive single author review articles, but large prospective clinical trials comparing treatment outcomes in veterinary medicine are lacking. The objectives of this consensus statement therefore are to provide guidelines on both recommended diagnostic testing and treatment for various causes of UI in dogs. Specifically, pathophysiology directly related to the canine urinary system will be reviewed and diagnostic and therapeutic challenges will be addressed. A panel of 12 experts in the field (8 small animal internists [L. Adams, J. Bartges, A. Berent, J. Byron, J. Foster, A. Kendall, S. Vaden, J. Westropp], 2 neurologists [J. Coates, N. Olby], 1 radiologist [G. Oetelaar], and 1 surgeon [C. Adin]) was formed to assess and summarize evidence in the peer-reviewed literature and to complement it with consensus recommendations using the Delphi method. Some statements were not voted on by all panelists. This consensus statement aims to provide guidance for management of both male and female dogs with underlying storage or voiding disorders resulting in UI.

Nephrology in Veterinary Medicine.

Veterinary nephrology is a specialized field of veterinary medicine providing a high level of care for animals with all types of kidney disease. Veterinarians complete extensive training to become board-certified in veterinary nephrology-urology. Companion animal nephrology is the most advanced field; however, all species are afflicted by a variety of renal disorders. Most naturally occurring animal kidney diseases have similar disorders found in people; where veterinary research is lacking, clinical management is often modified from standard of care in people. Veterinarians have become adept at scaling down procedures to safely perform them on dogs and cats weighing only a few kilograms. Advanced diagnostics (renal biopsy, cystoscopy, fluoroscopic studies, etc. ) and therapeutics (renal replacement therapy, interventional endourology, etc. ) are commonly performed within the practice of veterinary nephrology-urology. Collaboration between veterinary and human nephrologists may advance both disciplines and improve care for people and animals alike.

Adeno-associated virus-vectored erythropoietin gene therapy for anemia in cats with chronic kidney disease.

BACKGROUND: A treatment of chronic kidney disease (CKD)-associated anemia in cats is needed. SB-001 is an adeno-associated virus-vectored (AAV)-based gene therapeutic agent that is administered intramuscularly, causing the expression of feline erythropoietin. HYPOTHESIS/OBJECTIVE: We hypothesized that SB-001 injection would lead to a sustained increase in PCV in cats with CKD-associated anemia. ANIMALS: Twenty-three cats with International Renal Interest Society (IRIS) Stage 2 to 4 CKD-associated anemia were enrolled at 4 veterinary clinics. METHODS: In a prospective clinical trial, cats were treated with 1 of 3 regimens of SB-001 (Lo 1.2 × 109 genome copies [GCs] on Day 0; Lo ± Hi [supplemental 2nd dose of 3.65 × 109 GC on Day 42]; Hi 3.65 × 109 GC IM on Day 0) and followed for 70 days. RESULTS: A response to SB-001 at any time between Day 28 and Day 70 was seen in 86% (95% confidence interval 65, 97%) of all cats. There was a significant (P < .003) increase in PCV from Day 0 to Day 28 (mean increase 6 ± 6 percentage points [pp]; n = 21), Day 42 (8 ± 9 pp; n = 21), Day 56 (10 ± 11 pp; n = 17), and Day 70 (13 ± 14 pp, n = 14). Twelve cats were hypertensive at baseline, 4 of which developed encephalopathy during the study. An additional 6 cats became hypertensive during the study. CONCLUSIONS AND CLINICAL IMPORTANCE: Results of this study suggest that SB-001 therapy represents a suitable single injection treatment that can address nonregenerative anemia in cats with CKD. It was generally well tolerated; however, hypertension and encephalopathy developed in some cats as previously described in association with erythropoiesis-stimulating agent therapy.

Population pharmacokinetic analysis of enrofloxacin and its active metabolite ciprofloxacin after intravenous injection to cats with reduced kidney function.

BACKGROUND: It is unknown if enrofloxacin accumulates in plasma of cats with reduced kidney function. HYPOTHESIS: To determine if enrofloxacin and its active metabolite ciprofloxacin have reduced clearance in azotemic cats. ANIMALS: Thirty-four cats hospitalized for clinical illness with variable degree of kidney function. METHODS: Prospective study. After enrofloxacin (dose 5 mg/kg) administration to cats, sparse blood sampling was used to obtain 2 compartment population pharmacokinetic results using nonlinear mixed-effects modeling. Plasma enrofloxacin and ciprofloxacin concentrations were measured and summed to obtain the total fluoroquinolone concentration. A model of ciprofloxacin metabolism from enrofloxacin was created and evaluated for covariate effects on clearance, volume of distribution, and the metabolic rate of ciprofloxacin generation from enrofloxacin. RESULTS: Body weight was the only covariate found to affect total fluoroquinolone volume of distribution (effect 1.63, SE 0.19, P < .01) and clearance (effect 1.63, SE 0.27, P < .01). Kidney function did not have a significant effect on total fluoroquinolone clearance (median 440.8 mL/kg/h (range 191.4-538.0 mL/kg/h) in cats with normal kidney function, 365.8 mL/kg/h (range 89.49-1092.0 mL/kg/h) in cats with moderate kidney dysfunction, and 308.5 mL/kg/h (range 140.20-480.0 mL/kg/h) in cats with severe kidney dysfunction (P = .64). Blood urea nitrogen concentration influenced the metabolic generation of ciprofloxacin from enrofloxacin (effect 0.51, SE 0.08, P < .01), but other markers of kidney function did not. CONCLUSIONS AND CLINICAL IMPORTANCE: Adjustment of enrofloxacin dosage is not indicated for azotemic cats.

Cognition and Cerebral Blood Flow After Extracranial Carotid Revascularization for Carotid Atherosclerosis: A Systematic Review.

PURPOSE: Extracranial atherosclerotic carotid stenosis is associated with inadequate cerebral blood flow (CBF) and cognitive dysfunction. The impact of extracranial carotid revascularization on cognition and how any cognitive change relates to changes in CBF are less clear. This review examines the effects of revascularization of extracranial carotid disease by carotid endarterectomy (CEA) or carotid stenting (CAS) on cognition, and how this relates to changes in CBF. METHODS: A systematic review of existing reports in the Medline, Embase, and Cochrane databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement recommendations. All original retrospective or prospective studies and clinical trials that compared pre- and postoperative cognitive function and CBF in patients with extracranial carotid stenosis who underwent CEA or CAS versus a control group, published between January 1985 and December 2022, were identified and considered eligible for inclusion in this study. FINDINGS: Seven studies (661 participants; 460 CEA or CAS) were identified. All were observational studies and of moderate to good methodologic quality. Six studies (619 participants; follow-up range 1 month to 2 years) demonstrated improvement in some cognitive domains following CEA or CAS, improvement in CBF following revascularization, and correlated some of these cognitive changes with changes in CBF. One study (42 participants; 3 months follow-up) found cognitive improvement following CEA, but found no improvement in CBF or any correlation between cognitive and CBF change. The literature however represented heterogenous study populations examining asymptomatic and/or symptomatic carotid stenosis, differing in treatment modality and criteria for control groups ranging from healthy volunteers to those with stenosis but not who underwent surgical revascularization, and finally, differing reporting methods. This heterogeneity precluded meta-analysis. IMPLICATIONS: Definitive conclusions are limited by variation in cognitive function assessment, timing of testing, and how these are correlated to CBF. However, research suggests a potential improvement in cognition which may be associated with improvement in CBF, particularly in those patients who have more significant CBF deficit at baseline. Further studies are required to better understand this association and provide a clearer picture of the cognitive effects of carotid revascularization.

Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study.

Objectives: A novel 'subscription-type' funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model. Methods: An online survey was sent to all infection consultants in NHS acute hospitals in England. Results: The response rate was 31.2% (235/753). Most consultants agreed the model is a welcome development (69.8%, 164/235), will improve treatment of drug-resistant infections (68.5%, 161/235) and will stimulate research and development of new antimicrobials (57.9%, 136/235). Consultants disagreed that the model would lead to reduced carbapenem use and reported increased use of cefiderocol post-implementation. The presence of an antimicrobial pharmacy team, requirement for preauthorization by infection specialists, antimicrobial stewardship ward rounds and education of infection specialists were considered the most effective antimicrobial stewardship interventions. Under the new model, 42.1% (99/235) of consultants would use these antimicrobials empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting).Significantly higher insurance and diversity values were given to model antimicrobials compared with established treatments for carbapenem-resistant infections, while meropenem recorded the highest enablement value. Use of both 'subscription-type' model drugs for a wide range of infection sites was reported. Respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC and cefiderocol for those producing MBLs and infections with Stenotrophomonas maltophilia, Acinetobacter spp. and Burkholderia cepacia. Conclusions: The 'subscription-type' model was viewed favourably by infection consultants in England.

Correlation between imaging findings on outpatient MR enterography (MRE) in adult patients with Crohn disease and progression to surgery within 5 years.

PURPOSE: To retrospectively evaluate which key imaging features described by SAR-AGA on outpatient surveillance MRE correlate with progression to surgery in adults with CD. METHODS: 52 CD patients imaged with outpatient MRE from 10/2015 to 12/2016 and with available clinical information were included. Two abdominal radiologists reviewed the MRE for the presence of active inflammation, intramural edema, restricted diffusion, stricture, probable stricture, ulceration, sacculation, simple fistula, complex fistula, sinus tract, inflammatory mass, abscess, perienteric inflammation, engorged vasa recta, fibrofatty proliferation, and perianal disease. Bowel wall thickness, length of bowel involvement, and degree of upstream dilation in strictures were quantified. Subsequent bowel resection, prior bowel surgery, and available laboratory values were recorded. The association between progression to surgery and imaging features was evaluated using a logistic regression model adjusting for demographics, prior bowel surgery, medication usage, and body mass index. RESULTS: 19.2% (10/52) of patients progressed to surgery. Restricted diffusion, greater degree of upstream dilation from stricture, complex fistula, perienteric inflammation, and fibrofatty proliferation were significantly more common in patients progressing to surgery (all p < 0.05). κ for these significant findings ranged 0.568-0.885. Patients progressing to surgery had longer length bowel involvement (p = 0.03). Platelet count, ESR, and fecal calprotectin were significantly higher, and serum albumin was significantly lower in patients progressing to surgery. Prior bowel surgery, sex, age, and all other parameters were similar. CONCLUSION: Radiologists should carefully describe bowel dilation upstream from strictures, penetrating and perienteric findings on outpatient MRE in CD patients, as these findings may herald progression to surgery.

Metal-Organic Framework Nanosheets as Templates to Enhance Performance in Semi-Crystalline Organic Photovoltaic Cells.

Optimizing the orientation, crystallinity, and domain size of components within organic photovoltaic (OPV) devices is key to maximizing their performance. Here a broadly applicable approach for enhancing the morphology of bulk heterojunction OPV devices using metal-organic nanosheets (MONs) as additives is demonstrated. It is shown that addition of porphyrin-based MONs to devices with fully amorphous donor polymers lead to small improvements in performance attributed to increased light absorption due to nanosheets. However, devices based on semi-crystalline polymers show remarkable improvements in power conversion efficiency (PCE), more than doubling in some cases compared to reference devices without nanosheets. In particular, this approach led to the development of PffBT4T2OD-MON-PCBM device with a PCE of 12.3%, which to the authors' knowledge is the highest performing fullerene based OPV device reported in literature to date. Detailed analysis of these devices shows that the presence of the nanosheets results in a higher fraction of face-on oriented polymer crystals in the films. These results therefore demonstrate the potential of this highly tunable class of two-dimensional nanomaterials as additives for enhancing the morphology, and therefore performance, of semi-crystalline organic electronic devices.

Post-exfoliation functionalisation of metal-organic framework nanosheets via click chemistry.

The liquid exfoliation of layered metal-organic frameworks (MOFs) to form nanosheets (MONs) exposes buried functional groups making them useful in a range of sensing and catalytic applications. Here we show how high yielding click reactions can be used post-exfoliation to systematically modify the surface chemistry of MONs allowing for tuning of their surface properties and their use in new applications. A layered amino-functionalised framework is converted through conventional post-synthetic functionalisation of the bulk MOF to form azide functionalised frameworks of up to >99% yield. Ultrasonic liquid exfoliation is then used to form few-layer nanosheets, which are further functionalised through post exfoliation functionalisation using Cu(I)-catalysed azide-alkyne cycloaddition reactions. Here we demonstrate the advantages of post-exfoliation functionalisation in enabling: (1) a range of functional groups to be incorporated in high yields; (2) tuning of nanosheet surface properties without the need for extensive recharacterisation; (3) the addition of fluorescent functional groups to enable their use in the sensing of hazardous nitrobenzene. We anticipate that the versatility of different functional groups that can be introduced through high yielding click reactions will lead to advances in the use of MONs and other 2D materials for a variety of applications.

Efficacy of probucol on cognitive function in Alzheimer's disease: study protocol for a double-blind, placebo-controlled, randomised phase II trial (PIA study).

INTRODUCTION: Preclinical, clinical and epidemiological studies support the hypothesis that aberrant systemic metabolism of amyloid beta (Aß) in the peripheral circulation is causally related to the development of Alzheimer's disease (AD). Specifically, recent studies suggest that increased plasma concentrations of lipoprotein-Aß compromise the brain microvasculature, resulting in extravasation and retention of the lipoprotein-Aß moiety. The latter results in an inflammatory response and neurodegeneration ensues. Probucol, a historic cholesterol-lowering drug, has been shown in murine models to suppress lipoprotein-Aß secretion, concomitant with maintaining blood-brain-barrier function, suppressing neurovascular inflammation and supporting cognitive function. This protocol details the probucol in Alzheimer's study, a drug intervention trial investigating if probucol has potential to attenuate cognitive decline, delay brain atrophy and reduce cerebral amyloid burden in patients with mild-to-moderate AD. METHODS AND ANALYSIS: The study is a phase II, randomised, placebo-controlled, double-blind single-site clinical trial held in Perth, Australia. The target sample is 314 participants with mild-to-moderate AD. Participants will be recruited and randomised (1:1) to a 104-week intervention consisting of placebo induction for 2 weeks followed by 102 weeks of probucol (Lorelco) or placebo. The primary outcome is changed in cognitive performance determined via the Alzheimer's Disease Assessment Scales-Cognitive Subscale test between baseline and 104 weeks. Secondary outcomes measures will be the change in brain structure and function, cerebral amyloid load, quality of life, and the safety and tolerability of Lorelco, after a 104week intervention. ETHICS AND DISSEMINATION: The study has been approved by the Bellberry Limited Human Research Ethics Committee (approval number: HREC2019-11-1063; Version 4, 6 October 2021). Informed consent will be obtained from participants prior to any study procedures being performed. The investigator group will disseminate study findings through peer-reviewed publications, key conferences and local stakeholder events. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000726853).

The Effects of Body Tempering on Force Production, Flexibility and Muscle Soreness in Collegiate Football Athletes.

There has been limited research to explore the use of body tempering and when the use of this modality would be most appropriate. This study aimed to determine if a body tempering intervention would be appropriate pre-exercise by examining its effects on perceived soreness, range of motion (ROM), and force production compared to an intervention of traditional stretching. The subjects for this study were ten Division 1 (D1) football linemen from Sacred Heart University (Age: 19.9 ± 1.5 years, body mass: 130.9 ± 12.0 kg, height: 188.4 ± 5.1 cm, training age: 8.0 ± 3.5 years). Subjects participated in three sessions with the first session being baseline testing. The second and third sessions involved the participants being randomized to receive either the body tempering or stretching intervention for the second session and then receiving the other intervention the final week. Soreness using a visual analog scale (VAS), ROM, counter movement jump (CMJ) peak force and jump height, static jump (SJ) peak force and jump height, and isometric mid-thigh pull max force production were assessed. The results of the study concluded that body tempering does not have a negative effect on muscle performance but did practically reduce perceived muscle soreness. Since body tempering is effective at reducing soreness in athletes, it can be recommended for athletes as part of their pre-exercise warmup without negatively effecting isometric or dynamic force production.

Multiple variants in XDH and MOCOS underlie xanthine urolithiasis in dogs.

Hereditary xanthinuria is a rare autosomal recessive disease caused by missense and loss of function variants in the xanthine dehydrogenase (XDH) or molybdenum cofactor sulfurase (MOCOS) genes. The aim of this study was to uncover variants underlying risk for xanthinuria in dogs. Affected dogs included two Manchester Terriers, three Cavalier King Charles Spaniels, an English Cocker Spaniel, a Dachshund, and a mixed-breed dog. Four putative causal variants were discovered: an XDH c.654G > A splice site variant that results in skipping of exon 8 (mixed-breed dog), a MOCOS c.232G > T splice site variant that results in skipping of exon 2 (Manchester Terriers), a MOCOS p.Leu46Pro missense variant (Dachshund), and a MOCOS p.Ala128Glyfs*30 frameshift variant that results in a premature stop codon (Cavalier King Charles Spaniels and English Cocker Spaniel). The two splice site variants suggest that the regions skipped are critical to the respective enzyme function, though protein misfolding is an alternative theory for loss of function. The MOCOS p.Leu46Pro variant has not been previously reported in human or other animal cases and provides novel data supporting this residue as critical to MOCOS function. All variants were present in the homozygous state in affected dogs, indicating an autosomal recessive mode of inheritance. Allele frequencies of these variants in breed-specific populations ranged from 0 to 0.18. In conclusion, multiple diverse variants appear to be responsible for hereditary xanthinuria in dogs.

Retrospective Assessment of the Impact of Primary Language Video Instructions on Image Quality of Abdominal MRI.

PURPOSE: To assess the impact of instructional videos in patients' primary language on abdominal MR image quality for whom English is a second language (ESL). METHODS: Twenty-nine ESL patients viewed Spanish or Mandarin Chinese instructional videos (approximately 2.5 min in duration) in the preparation room before abdominal MRI (ESL-video group). Comparison groups included 50 ESL patients who underwent MRI before video implementation (ESL-no video group) and 81 English-speaking patients who were matched for age, sex, magnet strength, and history of prior MRI with patients in the first two groups. Three radiologists independently assessed respiratory motion and image quality on turbo spin-echo T2-weighted images (T2WI) and postcontrast T1-weighted images (T1WI) using 1 to 5 Likert scales. Groups were compared using Kruskal-Wallis tests as well as generalized estimating equations (GEEs) to adjust for possible confounders. RESULTS: For T2WI respiratory motion and T2WI overall image quality, Likert scores of the ESL-no video group (mean score across readers of 2.6 ± 0.1 and 2.6 ± 0.1) were lower (all P < .001) compared with English-speaking (3.3 ± 0.2 and 3.3 ± 0.1) and ESL-video (3.2 ± 0.1 and 3.0 ± 0.2) groups. In the GEE model, mean T2WI respiratory motion (both adjusted P < .001) and T2WI overall quality (adjusted P = .03 and .11) were higher in English and ESL-video groups compared with ESL-no video group. For T1WI respiratory motion and T1WI overall image quality, Likert scores were not different between groups (P > .05), including in the GEE model (adjusted P > .05). CONCLUSION: Providing ESL patients with an instructional video in their primary language before abdominal MRI is an effective intervention to improve imaging quality.

Monolayer nanosheets formed by liquid exfoliation of charge-assisted hydrogen-bonded frameworks.

Hydrogen-bonded organic frameworks (HOFs) are a diverse and tunable class of materials, but their potential as free-standing two-dimensional nanomaterials has yet to be explored. Here we report the self-assembly of two layered hydrogen-bonded frameworks based on strong, charge-assisted hydrogen-bonding between carboxylate and amidinium groups. Ultrasound-assisted liquid exfoliation of both materials readily produces monolayer hydrogen-bonded organic nanosheets (HONs) with micron-sized lateral dimensions. The HONs show remarkable stability and maintain their extended crystallinity and monolayer structures even after being suspended in water at 80 °C for three days. These systems also exhibit efficient fluorescence quenching of an organic dye in organic solvents, superior to the quenching ability of the bulk frameworks. We anticipate that this approach will provide a route towards a diverse new family of molecular two-dimensional materials.