Enzymatic conversion of human blood group A kidneys to universal blood group O.

ABO blood group compatibility restrictions present the first barrier to donor-recipient matching in kidney transplantation. Here, we present the use of two enzymes, FpGalNAc deacetylase and FpGalactosaminidase, from the bacterium Flavonifractor plautii to enzymatically convert blood group A antigens from the renal vasculature of human kidneys to 'universal' O-type. Using normothermic machine perfusion (NMP) and hypothermic machine perfusion (HMP) strategies, we demonstrate blood group A antigen loss of approximately 80% in as little as 2 h NMP and HMP. Furthermore, we show that treated kidneys do not bind circulating anti-A antibodies in an ex vivo model of ABO-incompatible transplantation and do not activate the classical complement pathway. This strategy presents a solution to the donor organ shortage crisis with the potential for direct clinical translation to reduce waiting times for patients with end stage renal disease.

An online survey capturing the views of stakeholders on primary school food systems across the four UK nations.

BACKGROUND: In 2020, the Generating Excellent Nutrition in UK Schools (GENIUS) Network was established to develop an understanding of the school food system across the four UK nations. This study explores stakeholders' views (headteachers, teachers, parents and pupils) on what works well, the challenges, and what an ideal primary school food system includes. METHODS: An online 'School Food Survey' was created in Qualtrics XM including closed and open-ended questions about the primary school food system. The Qualtrics link was distributed to stakeholders with an interest in school food through key contacts and networks across the four UK nations (21st June to 21st July and September 2021). Responses from the open-ended questions were exported from Qualtrics into Excel and analysed using SPSS. Aspects of qualitative content analysis were applied to summarise, code and quantify responses. Identified codes were entered by stakeholder, for example, parents and their response to the question into a Matrix table to allow identification of categories, themes and interpretation. RESULTS: A total of 509 participants completed the survey: most participants were from Scotland (n = 281; 55%) and England (n = 213; 42%) and were parents (n = 394). There were some consistent views across stakeholder responses, for example, the range of healthy options, costs, and portion sizes offered to pupils. Parents views varied, with some expressing the range of healthy options worked well and others reporting too many unhealthy choices. The cost of school food and school food funding presented challenges for both parents and schools. For parents, an ideal school food system would include a wide variety of fresh healthy food choices that were made on site, use quality produce, be inclusive for all cultures and diets, and provide food portion sizes appropriate for pupils ages. CONCLUSIONS: The findings iterate the diversity and some inconsistencies between stakeholders, emphasising the complexity and competing tensions school food systems encounter. Parental involvement and consideration of school-level and national factors are important when identifying challenges, what works well and describing an ideal primary school food system.

Regulatory mechanisms to create healthier environments: planning appeals and hot food takeaways in England.

AIMS: To explore existing regulatory mechanisms to restrict hot food takeaway (HFT) outlets through further understanding processes at local and national levels. METHODS: The Planning Appeals Portal was utilised to identify recent HFT appeal cases across England between December 2016 and March 2020. Eight case study sites were identified using a purposive sampling technique and interviews carried out with 12 professionals involved in planning and health to explore perceptions of and including factors that may impact on the HFT appeal process. Additionally, documents applicable to each case were analysed and a survey completed by seven Local Authority (LA) health professionals. To confirm findings, interpretation meetings were conducted with participants and a wider group of planning and public health professionals, including a representative from the Planning Inspectorate. RESULTS: Eight case study sites were identified, and 12 interviews conducted. Participants perceived that LAs would be better able to work on HFT appeal cases if professionals had a good understanding of the planning process/the application of local planning policy and supplementary planning documents; adequate time and capacity to deal with appeals cases; access to accurate, robust, and up to date information; support and commitment from elected members and senior management; good lines of communication with local groups/communities interested in the appeal; information and resources that are accessible and easy to interpret across professional groups. CONCLUSIONS: Communication across professional groups appeared to be a key factor in successfully defending decisions. Understanding the impact of takeaway outlets on health and communities in the long term was also important. To create a more robust appeals case and facilitate responsiveness, professionals involved in an appeal should know where to locate current records and statistical data. The enthusiasm of staff and support from senior management/elected officials will play a significant role in driving these agendas forward.

Opportunities for intervention and innovation in school food within UK schools.

We have recently been funded by the UK Prevention Research Partnership (UKPRP) to develop a UK school food network. The overarching aim is to build a community working towards a more health-promoting food and nutrition system in UK schools (primary and secondary). Here we describe the current status of school food research, including a review of the literature supporting the health-promoting schools approach and outline the opportunities for intervention and innovation establishment of the network present. Key potential school food research themes are described, and their prioritisation within the network, as well as network activities that have been planned, with the ultimate ambition of reducing socio-economic diet-related inequalities, and, consequently, non-communicable disease risk.

Electrolyte measurements differ between point-of-care and reference analysers in dogs with hypoadrenocorticism.

INTRODUCTION: Dogs treated for hypoadrenocorticism are monitored through analysis of their blood electrolytes. This is routinely performed with point-of-care analysers and doses of medications are adjusted based on the results. OBJECTIVES: To investigate the performance of two point-of-care analysers (IDEXX Catalyst Dx and IDEXX VetStat) against a reference laboratory method for the measurement of blood sodium, potassium and chloride concentrations, as well as sodium: potassium ratios, in dogs diagnosed with and treated for hypoadrenocorticism. METHODS: Forty-eight dogs were enrolled into a prospective cross-sectional study. Paired blood samples were taken and tested on two point-of-care analysers and at a reference laboratory. Statistical analysis was then performed with Bland-Altman analysis and Passing-Bablok regression. The clinical effects of inaccurate electrolyte analysis were investigated. RESULTS: In total, 329 samples were tested on the Catalyst analyser, while another 72 samples were tested on the VetStat. Passing-Bablok regression identified both proportional and constant bias for some analytes. There was poor agreement between sodium and chloride concentrations on both analysers. Both analysers tended to give higher results than the reference method for all analytes, except for potassium when measured on the VetStat. CLINICAL SIGNIFICANCE: There are inherent differences between the electrolyte concentrations measured by these two point-of-care analysers and reference laboratory methods in dogs with hypoadrenocorticism.

The occurrence of cardiac abnormalities in canine steroid-responsive meningitis arteritis.

OBJECTIVES: To document the prevalence of cardiac abnormalities in dogs with steroid-responsive meningitis arteritis and to assess resolution of these abnormalities following corticosteroid therapy. MATERIALS AND METHODS: Steroid-responsive meningitis arteritis was diagnosed based on signalment, physical examination findings, complete blood count, biochemistry and CSF analysis. Echocardiography, C-reactive protein and cardiac troponin I were measured in all cases before and 10 to 14 days after commencing corticosteroid therapy. Fibrinogen was also measured in a proportion of dogs. RESULTS: Fourteen dogs were prospectively enrolled. Increased cardiac troponin I was identified in five of 14 dogs and echocardiographic abnormalities were detected in 12 of 14 dogs, including spontaneous echo contrast (12 of 14), mild pericardial effusion (five of 14) and mildly decreased fractional shortening (five of 14). All dogs had increased C-reactive protein and fibrinogen was increased in 11 of 12. Corticosteroid treatment was associated with clinical improvement and normalisation of C-reactive protein in all dogs. The cardiac troponin I levels normalised in four of five and fibrinogen had normalised in all five dogs which were retested. Spontaneous echo contrast improved or completely resolved in 12 of 12 and pericardial effusion resolved in five of five dogs. Fractional shortening normalised in two of five dogs. CLINICAL SIGNIFICANCE: Cardiac changes are common in dogs with steroid-responsive meningitis arteritis and most resolve with therapy. Further investigation into the cause and significance of these changes is necessary in determining whether antithrombotic therapy or positive inotropic therapy is indicated.

The evolving contribution of non-communicable diseases to maternal mortality in Jamaica, 1998-2015: a population-based study.

OBJECTIVE: To describe trends in indirect cause-specific pregnancy-related mortality from 1998 to 2015. DESIGN: Secondary analysis of annual, national cross-sectional database of maternal and late maternal deaths, identified through active surveillance of deaths among women aged 10-50 years. SETTING: Jamaica, a middle-income Caribbean country. POPULATION: Maternal and late maternal deaths. METHODS: Descriptive trend analyses of demographic and cause-specific maternal and pregnancy-related mortality ratios undertaken comparing the periods 1998-2003, 2004-2009 and 2010-2015. Multivariate logistic regression was used to confirm changes in risk of indirect death. MAIN OUTCOME MEASURES: Maternal, pregnancy-related, direct, indirect and cause-specific mortality ratios (deaths/100 000 live births). RESULTS: Maternal deaths from indirect conditions increased between the first two periods (P = 0.004) and stabilised in the third (P = 0.085). Associated with upward movement in cardiovascular deaths (P[trend] = 0.003), women under 25 years were at elevated risk (odds ratio 1.44, 95% CI 1.00-2.08; P = 0.052). Haematological/immunological conditions (69% sickle cell disease) ranked second but did not vary with time. Health service utilisation was similar across age, parity, health region and major cause categories (non-communicable diseases, non-obstetric infections, direct), however women with indirect conditions spent more time in hospital (median 5 days versus 3 days) and more often died after the puerperium. CONCLUSIONS: Medical conditions, especially cardiovascular disease, are increasingly associated with maternal and late maternal mortality. Middle-income countries need to simultaneously improve management of indirect conditions, while redoubling efforts to reduce direct deaths. Postpuerperal medical services should be integrated into routine infant health services to improve continuity of care during this high-risk period. TWEETABLE ABSTRACT: Maternal survival (SDG 3.1) in LMICs requires better care for women with both non-communicable diseases and obstetric conditions.

Hair nicotine concentration measurement in cats and its relationship to owner-reported environmental tobacco smoke exposure.

OBJECTIVES: To investigate the association between hair nicotine concentration in cats and owner-reported exposure to environmental tobacco smoke. MATERIALS AND METHODS: Owner questionnaires documented exposure. Nicotine was extracted from hair by sonification in methanol followed by hydrophilic interaction chromatography with mass spectrometry. Relationships between hair nicotine concentration and owner-reported exposure were examined using hypothesis-testing statistics and receiver operating characteristic curve analysis. RESULTS: The hair nicotine concentration of reportedly exposed cats was significantly higher than unexposed cats and groups of cats with different levels of exposure had significantly different median hair nicotine concentrations corresponding to exposure. A hair nicotine concentration of 0·1 ng/mg had a specificity of 98% (95% confidence interval: 83 to 100) and a sensitivity of 69% (95% confidence interval: 54 to 84) for detecting environmental tobacco smoke exposure. Outdoors access, coat colour, urban or rural environment and length of time living with the owner were not obviously associated with hair nicotine concentration. CLINICAL SIGNIFICANCE: Feline hair nicotine concentration appears strongly associated with owner-reported environmental tobacco smoke exposure. Feline hair nicotine concentration could therefore be used as a biomarker for tobacco smoke exposure, allowing future studies to assess whether exposed cats have an increased risk of specific diseases.

Ray tracing analysis of a two-dimensional rectangular optical cavity for enhancing detector efficiency.

High detector efficiency has broad appeal and includes such diverse fields as quantum optics and solar energy. An optical resonator can improve detector efficiency by employing multiple re-reflections to the detector. This short paper uses geometric ray tracing to examine-for a given entry port size-the probability that a photon will escape from an ideal perfectly reflective two-dimensional cavity.

Nest building is a novel method for indexing severity of alcohol withdrawal in mice.

Withdrawal after chronic ethanol (EtOH) affects body temperature, goal-directed behavior and motor function in mice and increases general central nervous system excitability. Nest-building tests have been used to assay these states but to this point have not been employed as measures of EtOH withdrawal severity. We first refined nest-scoring methods using a genetically heterogeneous stock of mice (HS/Npt). Mice were then made physically dependent following three days of chronic EtOH vapor inhalation to produce average blood EtOH concentrations (BECs) of 1.89 mg/mL. EtOH withdrawal affected the progression of nest building over time when mice were tested 2-4 days after removal from three days of chronic exposure to EtOH. In a separate group of mice, chronic EtOH vapor inhalation (BECs 1.84 mg/mL) suppressed nest building over days 1-2 but not days 2-3 of withdrawal. In a following experiment, EtOH withdrawal dose-dependently slowed recovery of nest building for up to 32 h. Finally, we determined that long-lasting nest-building deficits extend to mice undergoing withdrawal from a high dose (4 g/kg) of acute EtOH. Sex differences for nest building were absent following EtOH exposure. In mice naïve to EtOH treatments, male mice had lower pre-test body temperatures and increased nest scores across a two-day testing period compared to females. These results suggest that nest building can be used to assess chronic and acute EtOH withdrawal severity in mice.

Weak value amplification of an off-resonance Goos-Hänchen shift in a Kretschmann-Raether surface plasmon resonance device.

During the past two decades there has been increased interest in the optical excitation of surface plasmon resonance (SPR) at a metal-dielectric interface. This is due in large part to its potential applications in such areas as medical diagnostics and pharmaceutical research. Also occurring during this time has been a growing recognition by the quantum physics community that weak value amplification (WVA) can serve as a valuable metrological research resource. Recently WVA has been used to amplify very small optical Goos-Hänchen (GH) shifts in glass and it has also been shown that SPR can greatly enhance optical GH shifts at the metal/air interface in Kretschmann-Raether (KR) devices. This paper demonstrates experimentally the WVA of an off-resonance GH shift in a KR device and explains why WVA of sufficiently SPR enhanced optical GH shifts cannot be achieved.

Nanoencapsulation of ABT-737 and camptothecin enhances their clinical potential through synergistic antitumor effects and reduction of systemic toxicity.

The simultaneous delivery of multiple cancer drugs in combination therapies to achieve optimal therapeutic effects in patients can be challenging. This study investigated whether co-encapsulation of the BH3-mimetic ABT-737 and the topoisomerase I inhibitor camptothecin (CPT) in PEGylated polymeric nanoparticles (NPs) was a viable strategy for overcoming their clinical limitations and to deliver both compounds at optimal ratios. We found that thrombocytopenia induced by exposure to ABT-737 was diminished through its encapsulation in NPs. Similarly, CPT-associated leukopenia and gastrointestinal toxicity were reduced compared with the administration of free CPT. In addition to the reduction of dose-limiting side effects, the co-encapsulation of both anticancer compounds in a single NP produced synergistic induction of apoptosis in both in vitro and in vivo colorectal cancer models. This strategy may widen the therapeutic window of these and other drugs and may enhance the clinical efficacy of synergistic drug combinations.

Twenty-eight day Holter monitoring is poorly tolerated and insensitive for paroxysmal atrial fibrillation detection in cryptogenic stroke.

This pilot study in a prospective cohort of 20 cryptogenic stroke patients showed that a significant proportion has paroxysmal atrial fibrillation undetected by 24-h Holter monitoring. However, longer monitoring with 28-day Holter was poorly tolerated and still insufficiently sensitive for paroxysmal atrial fibrillation detection. Further studies are urgently needed to elucidate the optimal timing, method and duration of cardiac rhythm monitoring following ischaemic stroke.

Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice.

Drinking in the dark (DID) is a limited access ethanol-drinking phenotype in mice. High Drinking in the Dark (HDID-1) mice have been bred for 27 selected generations (S27) for elevated blood ethanol concentrations (BECs) after a 4-h period of access to 20% ethanol. A second replicate line (HDID-2) was started later from the same founder population and is currently in S20. An initial report of response to selection in HDID-1 was published after S11. This article reports genetic and behavioral characteristics of both lines in comparison with the HS controls. Heritability is low in both replicates (h(2) = 0.09) but the lines have shown 4-5 fold increases in BEC since S0; 80% of HDID-1 and 60% of HDID-2 mice reach BECs greater than 1.0 mg/ml. Several hours after a DID test, HDID mice show mild signs of withdrawal. Although not considered during selection, intake of ethanol (g/kg) during the DID test increased by approximately 80% in HDID-1 and 60% in HDID-2. Common genetic influences were more important than environmental influences in determining the similarity between BEC and intake for HDID mice. Analysis of the partitioning of intake showed that 60% of intake is concentrated in the last 2 h of the 4 h session. However, this has not changed during selection. Hourly BECs during the DID test reach peak levels after 3 or 4 h of drinking. HDID mice do not differ from HS mice in their rate of elimination of an acute dose of alcohol.

Weak value amplification of an optical Faraday differential refraction effect.

In the presence of a longitudinal magnetic field B, a beam of linearly polarized light incident from a Faraday medium of Verdet constant V refracts at its interface with a medium of negligible Verdet constant and emerges as two opposite circularly polarized beams that are separated by a small divergence angle δ that is proportional to the product BV. Judicious postselection of the polarization state of the emergent light can be used to amplify the measured value of δ by several orders of magnitude. This technique makes it possible to optically measure either very small V values when B is known or small magnetic fields when V is known.

Multiple hepatic artery aneurysms in a patient with systemic lupus erythematosus.

UNLABELLED: Systemic vasculitis is a known complication of patients with systemic lupus erythematosus (SLE). Inflammation of the vessels can result in the development of arterial aneurysms with a potential risk of rupture or bleeding. CASE HISTORY: We present the case of a 56-year-old woman with SLE who developed three episodes of gastrointestinal (GI) bleeding without evidence of lesions in the GI tract. Multiple aneurysms of the hepatic artery were identified and treated with endovascular embolization, with no further GI bleeding. After embolization, the patient developed multiple bilomas that required percutaneous drainage, and subsequent abscesses which eventually resolved without further complications. CONCLUSION: Hepatic aneurysms, possibly secondary to vasculitis, may cause GI bleeding, and should be suspected in patients with SLE and GI bleeding with no apparent cause identifiable through standard endoscopy of the upper and lower GI tract.

Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder.

Our knowledge about the neurobiology of suicide is limited. It has been proposed that suicidal behavior generally requires biological abnormalities concomitant with the personality trait of impulsivity/aggression, besides an acute psychiatric illness or psychosocial stressor. We investigated fronto-limbic anatomical brain abnormalities in suicidal and non-suicidal adult female patients with unipolar depression. Our sample consisted of seven suicidal unipolar patients, 10 non-suicidal unipolar patients and 17 healthy female comparison subjects. The criterion for suicidality was one or more documented lifetime suicide attempts. A 1.5T GE Signa Imaging System running version Signa 5.4.3 software was used to acquire the magnetic resonance imaging images. All anatomical structures were measured blindly, with the subjects' identities and group assignments masked. We used analysis of covariance with age and intracranial volume as covariates and the Tukey-Kramer procedure to compare suicidal patients, non-suicidal patients and healthy comparison subjects. Suicidal patients had smaller right and left orbitofrontal cortex gray matter volumes compared with healthy comparison subjects. Suicidal patients had larger right amygdala volumes than non-suicidal patients. Abnormalities in the orbitofrontal cortex and amygdala in suicidal patients may impair decision-making and predispose these patients to act more impulsively and to attempt suicide.

Mass screening for antimicrobial resistant Escherichia coli in dairy cows in northern New South Wales.

OBJECTIVE: To describe aspects of the epidemiology of antimicrobial resistance in Escherichia coli shed in the faeces of milking cows in a dairying region of New South Wales. DESIGN: A survey based on multi-stage sampling with repeated measures made within herds for estimating within-herd correlation of resistance status, and with repeated measures made on identical specimens for estimating test-retest reliability. PROCEDURE: From a population of 110 dairy herds, 30 were selected at random and from each herd between 5 and 10 faecal specimens were obtained from fresh manure pats. E coli from faecal specimens were grown on hydrophobic grid membrane filters (HGMF) and replicated onto chromogenic agar and agar containing antimicrobials (gentamicin, ampicillin, tetracycline and sulfamethoxazole). Image analysis was used to assess colony growth. Data were analysed descriptively, by generalised linear mixed models and by Taylor series linearisation to account for attributes of the survey design. RESULTS: Of the 10,279 E coli isolates assessed, 91% expressed no resistance, 7.3% were resistant to sulfamethoxazole, 3.6% to tetracycline, 2.2% to ampicillin and 0.09% to gentamicin. The most common multiple resistance phenotype was ampicillin-tetracycline-sulfamethoxazole (1.8% of isolates). Most multiple resistant isolates appeared clustered within particular herds but were too rare to obtain valid estimates of variance, confidence intervals or intra-herd correlation. The estimated proportion of isolates in the population that were susceptible to all four antimicrobials was 97% (95% CI: 91% to 100%) and 55% of cows had no resistance detected in faecal E coli (95% CI: 27% to 83%). Within-herd correlation of shedding status (any resistance pattern) was absent and test-retest reliability of the measurement system was estimated to be at the lower end of good (0.40) but increased to excellent (0.89) after excluding sulfamethoxazole resistance, which had a greater measurement error. CONCLUSION: Antimicrobial resistance was uncommon in E coli in the population of dairy cows studied. HGMF and image analysis is an effective tool for detecting rare forms of resistant E coli that are not uniformly distributed in livestock populations.