Early Animal Origin of BACE1 APP/Aß Proteolytic Function.

Alzheimer's disease is characterized, in part, by the accumulation of ß-amyloid (Aß) in the brain. Aß is produced via the proteolysis of APP by BACE1 and γ-secretase. Since BACE1 is the rate-limiting enzyme in the production of Aß, and a target for therapeutics, it is of interest to know when its proteolytic function evolved and for what purpose. Here, we take a functional evolutionary approach to show that BACE1 likely evolved from a gene duplication event near the base of the animal clade and that BACE1 APP/Aß proteolytic function evolved during early animal diversification, hundreds of millions of years before the evolution of the APP/Aß substrate. Our examination of BACE1 APP/Aß proteolytic function includes cnidarians, ctenophores, and choanoflagellates. The most basal BACE1 ortholog is found in cnidarians, while ctenophores, placozoa, and choanoflagellates have genes equally orthologous to BACE1 and BACE2. BACE1 from a cnidarian (Hydra) can cleave APP to release Aß, pushing back the date of the origin of its function to near the origin of animals. We tested more divergent BACE1/2 genes from a ctenophore (Mnemiopsis) and a choanoflagellate (Monosiga), and neither has this activity. These findings indicate that the specific proteolytic function of BACE1 evolved during the very earliest diversification of animals, most likely after a gene-duplication event.

Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma.

The sub-ventricular zone (SVZ) is the most well-characterized neurogenic area in the mammalian brain. We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and emergence of recurrence. Here, we built a single-nucleus RNA-sequencing-based microenvironment landscape of the tumor mass (T_Mass) and the SVZ (T_SVZ) of 15 GBM patients and 2 histologically normal SVZ (N_SVZ) samples as controls. We identified a mesenchymal signature in the T_SVZ of GBM patients: tumor cells from the T_SVZ relied on the ZEB1 regulatory network, whereas tumor cells in the T_Mass relied on the TEAD1 regulatory network. Moreover, the T_SVZ microenvironment was predominantly characterized by tumor-supportive microglia, which spatially co-exist and establish heterotypic interactions with tumor cells. Lastly, differential gene expression analyses, predictions of ligand-receptor and incoming/outgoing interactions, and functional assays revealed that the IL-1ß/IL-1RAcP and Wnt-5a/Frizzled-3 pathways are therapeutic targets in the T_SVZ microenvironment. Our data provide insights into the biology of the SVZ in GBM patients and identify specific targets of this microenvironment.

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

A further case of chondrodysplasia with growth failure occurring after hematopoietic stem cell transplantation (HSCT).

There is an emerging body of evidence showing that young patients, post haematopoietic stem cell transplantation (HSCT), can develop skeletal changes that mimic an osteochondrodysplasia process. The key discriminator is that these children have had otherwise normal growth and skeletal development before the therapeutic intervention (HSCT), typically for a haematological malignancy. Herein we present that case of a boy who underwent HSCT for Haemophagocytic Lymphohistiocytosis (HLH) aged 2 years. Following Intervention with HSCT this boy's growth has severely decelerated (stature less than 1st centile matched for age) and he has developed a spondyloepiphyseal dysplasia.

Acoustic metasurfaces with Frieze symmetriesa).

Frieze patterns follow a set of tiling instructions including reflection, rotation, and translation, and tile the infinite strip. Many metamaterials function due to the underlying symmetry, and its strategic breaking, of their constituent sub-structures that allow tailoring of the dispersion of modes supported by the structure. We design, simulate, and experimentally characterize seven one-dimensional acoustic metasurfaces whose unit cells each belong to one of the distinct Frieze groups.

Cognitive function and the longitudinal hippocampal axis in mesial temporal sclerosis.

OBJECTIVE: The relationship of preoperative memory deficits in patients with mesial temporal lobe epilepsy (mTLE) and hippocampal sclerosis (HS) to the distribution of neuronal loss is uncertain. Building on the material specificity theory, we tested the hypothesis that visual memory deficits are associated with posterior hippocampal atrophy, whereas verbal memory deficits are associated with anterior hippocampal atrophy. METHODS: We studied 22 adults with mTLE and HS, calculating hippocampal head, body, and tail volumes, correcting for estimated total intracranial volume, using automated segmentation. Preoperative memory ability was evaluated with the Wechsler Memory Scale (WMS-II: logical memory, verbal paired associates, family pictures, and faces subtests). We correlated memory ability with hippocampal division volumes using SPSS 26.1 (repeated measures ANOVAs, one-way ANOVAs, Pearson r correlations) for statistical analysis. RESULTS: We found a significant main effect of hippocampal subdivision, reporting volumetric differences between the head, body, and tail. Pairwise comparisons reported that the hippocampal head had significantly greater volume than both the body and tail (p < 0.001). For both left and right focus groups, the ipsilateral hippocampi were significantly smaller than the contralateral. Linear regression reported a left hippocampal model (head, body, and tail volumes) predicted performance on logical memory with the left hippocampal tail volume being the strongest predictor. A right hippocampal model (head, body, and tail volumes) predicted memory ability for family pictures and verbal paired associates at a trend level. CONCLUSIONS: Ipsilateral hippocampal head and tail seem more vulnerable to injury than the body in both the left and right mTLE. Our study suggests there may be functional differences along the hippocampal longitudinal axis, particularly for the left hippocampal tail with verbal memory. Our findings are consistent with material-specific right-left differences in memory processing.

Evaluation of phytase dose effect on performance, bone mineralization, and prececal phosphorus digestibility in broilers fed diets with varying metabolizable energy, digestible amino acids, and available phosphorus concentration.

The nutritional composition of diets and the provision of exogenous phytases play important roles in animal performance. Therefore, we evaluated the individual and combined impact of metabolizable energy (ME), digestible lysine (dLys), available phosphorus (avP) and calcium (Ca), and phytase dose (1,000 or 2,000 FTU/kg) on the growth performance, feed efficiency, phosphorus digestibility, and bone ash content of broiler chickens from 10 to 42 d of age. Experimental diets were formulated in a Box-Behnken design to contain various levels of ME (11.9, 12.2, 12.54, or 13.1 MJ/kg), dLys (0.91, 0.93, 0.96, or 1.00%) and avP/Ca (0.12/0.47, 0.21/0.58, or 0.33/0.68%). The effect of phytase was expressed in terms of the extra nutrients released. The diets were formulated to have consistent phytate substrate contents (0.28% in average). Body weight gain (BWG) and feed conversion ratio (FCR) were described via polynomial equations (R2 = 0.88 and 0.52, respectively), with interconnections between variables (ME, dLys, and avP/Ca). No interaction was observed among variables (P > 0.05). Metabolizable energy was the most important factor affecting BWG and FCR (linearly; P < 0.001). Reducing ME content from 13.1 to 11.9 MJ/kg in control diet resulted in a 6.8% decrease in BWG and a 3.1% increase in FCR (P < 0.001). The dLys contents also affected performance linearly (P < 0.001), but to a lesser degree; BWG decreased by 160 g when the dLys was reduced by 0.09% units, while the same reduction in dLys increased the FCR by 0.108 points. The inclusion of phytase alleviated the negative effects on feed intake (FI), BWG, and FCR. Phytase improved phosphorus digestibility and bone ash content according to a quadratic relationship. When phytase was added, ME negatively affected FI (r = -0.82, P < 0.001), whereas the dLys content was correlated with FCR (r = -0.80, P < 0.001). Supplementing phytase allowed the reduction of ME, dLys, and avP-Ca in the diet without affecting performance. The addition of phytase increased of ME, dLys, and avP by 0.20 MJ/kg, 0.04 and 0.18% units for 1,000 FTU/kg and 0.4 MJ/kg, 0.06 and 0.20% units for 2,000 FTU/kg.

Neosporosis in Argentina: Past, present and future perspectives.

Neosporosis, caused by the protozoan Neospora caninum, was first diagnosed in Argentinean cattle in the 90's. With a national bovine stock of approximately 53 million head, the cattle industry is socially and economically relevant. Severe economic losses have been estimated at US$ 33 and 12 million annually in dairy and beef cattle, respectively. Approximately 9% of bovine abortions in the Buenos Aires province are caused by N. caninum. In 2001, the first isolation of N. caninum oocysts from feces of a naturally infected dog was performed in Argentina and named as NC-6 Argentina. Further strains were isolated from cattle (NC-Argentina LP1, NC-Argentina LP2) and axis deer (Axis axis, NC-Axis). Epidemiological studies revealed a high distribution of Neospora-infections not only in dairy but also in beef cattle, with seroprevalence rates of 16.6-88.8% and 0-73%, respectively. Several experimental infection studies in cattle have been carried out, as well as attempts to develop effective vaccines to avoid Neospora-abortions and transmission. However, no vaccine has proven successful for its use in daily practice. Reduction of seroprevalence, vertical transmission and Neospora-related abortions have been achieved in dairy farms by the use of selective breeding strategies and embryo transfer. Neospora-infections have been also detected in goats, sheep, deer, water buffaloes (Bubalus bubalis) and gray foxes (Lycalopex griseus). Moreover, Neospora-related reproductive losses were reported in small ruminants and deer species and could be more frequent than previously thought. Even though diagnostic methods have been improved during the last decades, control of neosporosis is still not optimal. The development of new strategies including new antiprotozoal drugs and vaccines is highly needed. This paper reviews the information from the previous 28 years of research of N. caninum in Argentina, including seroprevalence and epidemiological studies, available diagnostic techniques, experimental reproduction, immunization strategies, isolations and control measures in domestic and non-domestic animals from Argentina.

Performance and health of broiler chickens fed low erucic acid, lower fiber pennycress (CoverCressTM) grain.

CoverCress (low erucic acid, lower fiber pennycress) is being developed as a cover crop to be planted in the fall after corn and harvested in the spring prior to planting soybeans. Two experiments were conducted to evaluate 2 lines of the whole grain (CCWG-1: natural mutation and mutation breeding; CCWG-2: gene edited) and the whole grain pretreated with the potential palatability agent copper sulfate (CCWG-1-CuSO4; CCWG-2-CuSO4) as an ingredient for broilers. In Experiment 1, CCWG-1-CuSO4 was included in the diet at 0, 4, and 6% for 41 d. Feed intake, body weight gain, feed conversion, processing characteristics, organ weights, serum thyroid, macropathology and histology data were collected. In Experiment 2, broilers were fed diets containing Control, 2% CCWG-1, 4% CCWG-1, 4% CCWG-2, and 4.35% CCWG-1-CuSO4 for 42 d. Feed intake, body weight gain, feed conversion, organ weights, serum thyroid, blood chemistries, macropathology, and histology data were collected. In Experiment 1, feed intake and body weight were diminished with no effect on feed conversion for the birds consuming diets containing CCWG-1-CuSO4. In Experiment 2, feed intake and body weight were lower with no difference in feed conversion in birds fed diets containing greater than 2% CoverCress grain during d 0 to 28. During d 28 to 42 no difference in feed intake, body weight and an improvement in feed conversion was observed in birds fed all of the CoverCress grain products. In both experiments no significant negative effects were observed in processing, liver, kidney, and thyroid weights, T3, T4, blood chemistries, macropathology, and histopathology between the control and any of the CoverCress grain treatments. No difference in performance was observed in birds fed the mutant (4% CCWG-1) and gene-edited (4% CCWG-2) products. Pretreating CoverCress grain with copper sulfate did not have a significant effect on improving palatability. In conclusion, CoverCress grain can be safely fed to broilers when included at a target rate of 4% in diets and with total glucosinolate levels not to exceed 4.9 µmoles g-1.

Use and comparison of serologic assays to detect anti-Neospora caninum antibodies in farmed red deer (Cervus elaphus).

Neospora caninum is a protozoan parasite that cause abortion in different ruminant species, including red deer ( Cervus elaphus). There are no validated assays to be performed with sera from red deer. At the present work, we evaluated the agreement among indirect fluorescent antibody test (IFAT), competitive inhibition ELISA based on a recombinant protein (ciELISA tSAG1) and immunoblot (IB) to detect anti- N. caninum antibodies in a red deer herd that presented reproductive losses due to N. caninum. In addition, we analyzed the relationship between the serologic results and 15 hinds were analyzed by IFAT, ciELISA tSAG1 and IB to detect anti- N. caninum antibodies. In the three assays, the cut-off established for cattle was used. Besides, sera were analyzed by IFAT to detect anti- Toxoplasma gondii antibodies. The hinds were monitored by ultrasound scanning during the gestational period to detect abortions. Gwet's agreement coefficient (AC1) and the percentage of agreement were used to estimate the agreement between pairs of assays. Chi-square test and odds ratio (OR) were used for the statistical association between abortion and seropositivity to N. caninum or to T. gondii. The N. caninum seropositivity rate was 53.9% (62/115), 57.4% (66/115) and 55.7% (64/115) for IFAT, ciELISA tSAG1 and IB, respectively. The AC1 and percentage of agreement were 0.760% and 87.8% for the pair ciELISA tSAG1 /IFAT, 0.793% and 89.6% for the pair IFAT/IB, and 0.966% and 98.3% for the pair IB/ciELISA tSAG1. The T. gondii seropositivity rate was 53.0% (61/115). Seropositive hinds to N. caninum were more likely to abort than seronegative hinds by the 3 assays. The OR for the association between N. caninum seropositivity and abortion was 72.70, 22.96 and 83.24 when ciELISA tSAG1, IFAT or IB assays were used, respectively. between T. gondii seropositivity and abortion. The three serologic assays were useful to detect N. caninum infected hinds. The validation of the assays for use in red deer would be an improvement for diagnosis of neosporosis in this species.

Links Between Childhood Abuse, Insidious Trauma, and Methamphetamine Use Across the Lifespan Among Gay, Bisexual, and Other Men Who Have Sex with Men: A Qualitative Analysis.

Developmental and lifespan examinations of methamphetamine use among gay, bisexual, and other men who have sex with men (GBM) remain limited. We used a feminist trauma framework to examine potential links between childhood trauma, trauma-related stressors, and methamphetamine use among GBM. From June 2018 to October 2018, semi-structured interviews (N = 33) were conducted with GBM across British Columbia. Interviews focused on sexual experiences, support services, and methamphetamine use. Using thematic analysis, two overarching trauma-related themes were identified: developmental and insidious trauma and coping with trauma-related stressors. GBM's methamphetamine use co-occurred with childhood experiences of family- and peer-perpetrated heterosexism, childhood sexual abuse, and intersecting forms of oppression/marginalization. These experiences manifested as internalized shame, interpersonal anxiety, and low self-esteem. In adulthood, participants reported difficulty managing emotions, low self-confidence, and loneliness. GBM reported using methamphetamine to manage negative emotions, life stressors, and overcome barriers to interpersonal connection. Findings indicate a need for trauma-informed interventions that address underlying issues and help GBM cultivate supportive relationships.

Transcriptional changes detected in fecal RNA from neonatal dairy calves of different breeds following gastrointestinal disease of varying severity.

Gastrointestinal (GI) disease is a major health concern in preweaned dairy calves. The objective of this fixed cohort study was to use RNA isolated from preweaned Holstein and Jersey heifer calf feces to study the molecular adaptations to variable clinical GI disease. The study was conducted on a commercial calf ranch in the western U.S. Enrolled calves were assessed twice daily for variations in demeanor, milk intake, and hydration. Fecal consistency scores were recorded at enrollment (day 1), and on the day (day 10) that a fecal sample was collected for differential gene expression (DGE). Calves with diarrhea on either day were classified as having either uncomplicated, localized GI disease (scours), or systemic GI disease (systemic enteritis). Eighty-four calves' fecal RNA was evaluated for DGE, of which 33 calves (n = 20 Holstein; n = 13 Jersey) were consistently healthy. The remaining 51 calves (n = 23 Holstein; n = 28 Jersey) experienced varying severity of GI disease during the sampling window. Genes of interest were related to the inflammatory response (i.e., IFNG, NFKB1, NOD2, TLR2, and TLR4) and cell membrane or cytoplasmic transport (i.e., AQP3, FABP2, KRT8 and SLC5A1). Breed-specific findings indicated that AQP3, IFNG, and TLR4 were upregulated in Holsteins with systemic enteritis, whereas KRT8 was downregulated in systemically affected Jerseys. Holsteins did not appear affected by scours aside from a tendency for DGE of toll-like receptors (TLRs) on the day of diarrhea. However, Jersey calves consistently demonstrated a tendency to upregulate IFNG, NFKB1, and TLR4 when affected with either scours or systemic enteritis. These findings were more pronounced in systemically affected Jersey calves and were observed as a delayed response to both scours and systemic enteritis. These findings support previous observations suggesting that Holstein calves may be better equipped than Jersey calves to rapidly fight pathogen invasion.

The Greater Manchester Child Friendly Dental Practice Scheme: Using a Transformational Commissioning Approach to Align Paediatric Dental Service Provision with Childhood Oral Health Needs in Greater Manchester.

In response to the impact of the COVID-19 pandemic on access to already oversubscribed specialist paediatric dental services, a pilot of an enhanced primary care paediatric dental pathway, known as the Child Friendly Dental Practice (CFDP) scheme, was commissioned by the Greater Manchester Health and Social Care Partnership. Supported by a transformational commissioning approach, the ambition of the CFDP pilot was to manage or stabilise the oral health of high-need paediatric patients who had been referred to specialist dental services within Community or Hospital Dental Service settings, through timely access to primary care clinicians who were confident and experienced in treating children. The theory of change of the CFDP pilot proposed that rapid access to enhanced primary dental care would reduce the need for onward referral to specialist paediatric dental services, whilst also stabilising the oral health of children who require more complex management in specialist services. A formative evaluation of the phase one pilot implementation of the CFDP Scheme has demonstrated the potential of the CFDP Scheme to improve access to dental services for paediatric patients referred from their General Dental Practitioner. Comparison of waiting times between the CFDP pathway and the standard paediatric dental referral pathway have revealed substantially reduced waiting times to access care along the CFDP pathway, while less than 30% of those who attended CFDPs required onward referral to specialist paediatric dental services. Encouragingly, similar attendance and treatment completion rates were noted among patients from all levels of socio-economic deprivation, reducing concerns regarding the potential for service-based interventions to increase oral health inequalities. Following successful completion of the phase one pilot implementation and evaluation, the CFDP Scheme has now been rolled out across all localities in Greater Manchester as part of a second phase pilot implementation. Public Health Competencies; Equitable healthcare provision, Partnership working, Evidence-based public health, Systems thinking, Transformational commissioning, Healthcare evaluation.

Who are the 10%? Characteristics of the populations and communities receiving fluoridated water in England.

OBJECTIVES: In England, around 10% of the population receive optimally fluoridated water. This coverage has evolved through a combination of historical local decision-making and natural geography, rather than being strategically targeted at the national level. It is important to understand if the current distribution is equitable according to indicators of oral health need and to identify any population-level differences in socio-demographic characteristics that could introduce bias to studies evaluating the effectiveness of water fluoridation. BASIC RESEARCH DESIGN: Descriptive analysis comparing the census characteristics of populations that received optimally fluoridated (=/⟩ 0.7 mg F/L) and non-fluoridated water (⟨0.7 mg F/L) between 2009 and 2020. RESULTS: Populations receiving fluoridated water between 2009-2020 were on average slightly younger, more urban, more deprived, with lower education levels, higher unemployment and lower car and home ownership than the populations who received non-fluoridated water. They are more ethnically diverse, with a higher proportion of Asian ethnicity and a lower proportion of White ethnicity, compared to the non-fluoridated population. DISCUSSION: This descriptive analysis provides evidence that water fluoridation coverage within England is targeted reasonably equitably in relation to population-level indicators of need. It also confirms the need to consider the impact of underlying differences in age, deprivation, rurality, and ethnicity when evaluating the impact of water fluoridation on health outcomes in England.

Opportunities for Education in Heart Failure Pharmacotherapy Demonstrated by a Survey of Clinicians.

Aim We conducted a survey of practitioners' knowledge of the clinical application of the major drug classes in HF, with reference to the European Society of Cardiology guidelines. The aim was to identify areas for practice development through education, which may improve HF morbidity and mortality. Methods We distributed a 14 item questionnaire assessing doctors knowledge of indications and contraindications for the major HF drug classes. Results Total number of responses was 127: Intern (N=21), SHO (N=64), Registrar (N=12), SpR (N=14), Consultant (N=4), GP (N=2). Consultants and GPs were excluded from analysis due to underrepresentation. Median years of practice was 4. Indications were correctly identified in a mean of 78% of responses overall. Of participants who felt comfortable with initiation and up-titration of beta blockers (N=84), only 31% (N=26) correctly identified an optimal target heart rate of less than 70 beats per minute. Forty-five percent (N=50) identified serum potassium and creatinine concentrations generally considered safe as contraindications to the initiation of MRA. Twenty-five percent of respondents (N=28) were unaware of a specialist HF service that catered to their institution, and how to refer to it, but 99% (N=110) felt that their practice would benefit from further education on HF pharmacotherapy. Conclusion Results of this survey suggest a need, and indeed a demand, for further education for clinicians in order to reduce mortality, morbidity, and hospital readmission in HF, as well as their attendant costs.

Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network.

BACKGROUND: Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate. METHOD: This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada. RESULTS: The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers. CONCLUSION: The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.

Fate of thiamethoxam from treated seeds in mesocosms and response of aquatic invertebrate communities.

Thiamethoxam is a neonicotinoid insecticide widely applied in the Canadian Prairies. It has been detected in surface waters of agro-ecosystems, including wetlands, but the potential effects on non-target invertebrate communities in these wetlands have not been well characterized. In an effort to understand better the fate of thiamethoxam in wetlands and the response of invertebrates (zooplankton and emergent insects), model systems were used to mimic wetland flooding into planted fields. Outdoor mesocosms were treated with a single application of thiamethoxam-treated canola seeds at three treatment levels based on a recommended seeding rate (i.e., 6 kg/ha; 1×, 10×, and 100× seeding rate) and monitored over ten weeks. The mean half-life of thiamethoxam in the water column was 6.2 d. There was no ecologically meaningful impact on zooplankton abundances or community structure among treatments. Statistically significant differences were observed in aquatic insect abundance between control mesocosms and the two greatest thiamethoxam treatments (10× and 100× seeding rate). The observed results indicate exposure to thiamethoxam at environmentally relevant concentrations likely does not represent a significant ecological risk to abundance and community structure of wetland zooplankton and emergent insects.

Water fluoride concentrations in England, 2009-2020.

OBJECTIVES: Contemporary research, surveillance and monitoring of water fluoridation requires an understanding of the population coverage of this intervention. The aims of this research are to create the first publicly available record of water fluoride concentrations in England and to describe and visualise the observed variation in water fluoride concentrations and optimal fluoridation (⟩/= 0.7 mg F/L) between 2009-2020. BASIC RESEARCH DESIGN: Routine water quality sampling data were requested from water companies in England from 2009-2020 under the provisions of the Environmental Information Regulations 2004. Fluoride concentrations of Water Supply Zones (WSZs) were assigned to Lower Super Output Areas (LSOAs) using population-weighted centroids. RESULTS: Between 2009-2020 4247 LSOAs (12.9%) had an annual mean water fluoride concentration of ⟩/= 0.7 mg F/L in at least one year, and 3019 LSOAs (9.1%) had a grand mean fluoride concentration of ⟩/= 0.7 mg F/L. Coverage of optimal fluoridation varied over time; from 10.9% of LSOAs in 2014 to 6.3% in 2016. DISCUSSION: This study confirms previous work identifying variability in the coverage and achieved concentrations of water fluoridation programmes. The current provision for accessing, collating and utilising these data are a barrier to essential monitoring, surveillance and research. An annually maintained and publicly accessible database of water fluoride concentrations is urgently required.

Histological and immunohistochemical features suggesting aetiological differences in lymph node and (muco)cutaneous feline tuberculosis lesions.

OBJECTIVES: To identify and describe histological and immunohistochemical criteria that may differentiate between skin and lymph node lesions associated with Mycobacterium (M.) bovis and M. microti in a diagnostic pathology setting. MATERIALS AND METHODS: Archived skin and lymph node biopsies of tuberculous lesions were stained with haematoxylin and eosin, Ziehl-Neelsen and Masson's Trichrome. Immunohistochemistry was performed to detect the expression of calprotectin, CD3 and Pax5. Samples were scored for histological parameters (i.e. granulomas with central necrosis versus small granulomas without central necrosis, percentage necrosis and/or multinucleated giant cells), number of acid-fast bacilli (bacterial index) and lesion percentage of fibrosis and positive immunohistochemical staining. RESULTS: Twenty-two samples were examined (M. bovis n=11, M. microti n=11). When controlling for age, gender and tissue, feline M. bovis-associated lesions more often featured large multi-layered granulomas with central necrosis. Conversely, this presentation was infrequent in feline M. microti-associated lesions, where small granulomas without central necrosis predominated. The presence of an outer fibrous capsule was variable in both groups, as was the bacterial index. There were no differences in intralesional expression of immunohistochemical markers. CLINICAL SIGNIFICANCE: Differences in the histological appearance of skin and lymph node lesions may help to infer feline infection with either M. bovis or M. microti at an earlier stage when investigating these cases, informing clinicians of the potential zoonotic risk. Importantly, cases of tuberculosis can present with numerous acid-fast bacilli. This implies that a high bacterial index does not infer infection with non-zoonotic non-tuberculous mycobacteria.