A mixed-method process evaluation of an East Midlands county summer 2021 holiday activities and food programme highlighting the views of programme co-ordinators, providers, and parents.

Background: The Holiday Activities and Food (HAF) Programme is a UK Government initiative created to alleviate food insecurity and promote health and well-being among children and their families, who are eligible for Free School Meals (FSM), during the school holidays. This process evaluation investigated factors that facilitated and acted as a barrier to the delivery of the HAF Programme from the perspectives of key stakeholders (Co-ordinators, Providers, and Parents) involved in the HAF Programme across an East Midlands county. Methods: This evaluation utilized a mixed-methods approach, incorporating focus groups and online surveys to gain rich, multifaceted data. The focus groups were analyzed using a hybrid inductive-deductive thematic analysis and the online surveys were analyzed using mixed-methods approach due to the variation in question type (i.e., quantitative, Likert scale and open response) to align themes to the Government Aims and Standards of the HAF Programme. Findings: The stakeholders highlighted several factors that facilitated and acted as a barrier to the delivery of the HAF Programme. Facilitating factors included existing and maintaining relationships between Co-ordinators, Providers, and facilities/schools/communities as this improved communication and attendance. Additionally, transport provision for those attending the Programme helped overcome barriers to attendance. The primary barrier of the Programme was the late awarding of the Programme contract as this limited the time available to prepare and organize the Programme. This in turn, had several "knock on" effects that created more barriers and resulted in some of the Government Aims and Standards not being met such as, nutrition education for children and parents. Despite the challenges faced, Co-ordinators and Providers were able to deliver the Programme and positively impact upon the children and their families that attended the Programme. Conclusion: Following the facilitators and barriers that were highlighted in this evaluation, several recommendations have been made to enhance the delivery of the HAF Programme and ensure Government Aims and Standards, to improve children and family's health and well-being, are attained.

A requirement for cell elongation protein RodZ and cell division proteins FtsN and DedD to maintain the small rod morphology of Escherichia coli at growth temperatures near 8°C.

As similarly observed in nutrient-poor media at 37°C, Escherichia coli forms small rods in nutrient-rich media at temperatures near 8°C, the minimum temperature of growth. A study was initiated to identify proteins required to facilitate the small rod morphology at low temperature. E. coli contains three nonessential SPOR domain proteins (DamX, RlpA, and DedD) that have been demonstrated to bind to the septal ring. In contrast to the normal growth and small rod morphology of damX and rlpA null mutants at 10°C, the dedD null mutant exhibited reduced growth and formed filamentous cells. The presence of plasmid-encoded DedD restored growth and small rods. Plasmid-encoded FtsN, an essential SPOR domain protein that functions to stabilize the septal ring and to initiate septation, in the dedD null mutant resulted in increased growth and the formation of shorter chained cells. However, plasmid-encoded DedD failed to restore growth and cell division of cells lacking FtsN at 10°C. In contrast to cell division protein DedD, RodZ is a cell elongation protein particularly required for growth at 30°C. However, the rodZ null mutant grew similarly as the wild type strain and produced cocci in LB broth at 10°C. Moreover at 10°C, the concerted deletion of dedD and rodZ resulted in severe inhibition of growth accompanied with the formation of swollen prolate ellipsoids due to a block in septal ring assembly and cell elongation. The data indicate the cellular requirement of both FtsN and DedD for septation as well as RodZ for cell elongation to maintain the small rod morphology at temperatures near 8°C. In comparison to the growth and small rods of the wild type in M9-glucose minimal media at 37°C, the dedD null mutant grew at the same rate and produced elongated cells while the rodZ null mutant grew at a slightly slower rate and produced cocci. The data indicate that DedD and RodZ are also required to maintain the small rod morphology in nutrient-poor media, but there is a higher cellular requirement of DedD for growth and cell division in nutrient-rich media at low temperature.

Presence or absence of intestinal metaplasia but not its burden is associated with prevalent high-grade dysplasia and cancer in Barrett's esophagus.

Universal agreement on the inclusion of intestinal metaplasia to diagnose Barrett's esophagus (BE) is lacking. Our aim was to determine the association of intestinal metaplasia and its density with the prevalence of dysplasia/cancer in columnar lined esophagus (CLE). Patients with CLE but no intestinal metaplasia (CLE-no IM) were identified by querying the clinical pathology database using SNOMED codes for distal esophageal biopsies. CLE-IM patients were identified from a prospectively maintained database of BE patients. Subsequently, relative risks for prevalent dysplasia and cancer were calculated. Since patients with CLE-no IM are not usually enrolled in surveillance, only prevalent dysplasia/cancer on index endoscopy was analyzed. Goblet cell density and percent intestinal metaplasia were estimated. All biopsy slides were reviewed for dysplasia by two experienced gastrointestinal pathologists. Two hundred sixty-two CLE-IM and 260 CLE-no IM patients were included (age 64±12 vs. 60±11 years, P=0.001; whites 92% vs. 82%, P=0.001; males 99.7% vs. 99.3%, P=NS; CLE length 3.4±3.2 vears 1.4±0.4 cm, P=0.001 and hiatus hernia 64% vs. 56%, P=0.013). The odds of finding low-grade dysplasia and of high-grade dysplasia (HGD)/cancer were 12.5-fold (2.9-53.8, P=0.007) and 4.2-fold (95% CI 1.4-13, P=0.01) higher, respectively, in the CLE-IM group. Reanalysis after controlling for important variables of age, race, and length did not significantly alter the overall results. In CLE-IM group, when patients with high (>50/LPF) versus low goblet cell density (<50/LPF) and <10% versus >10% intestinal metaplasia were compared, the odds of HGD/cancer, OR 1.5 (0.5-4.9, P=0.5) and 1.97 (0.54-7.22), respectively, were not significantly higher. Demonstration of intestinal metaplasia continues to be an essential element in the definition of BE, but its quantification may not be useful for risk stratification of HGD/cancer in BE.

Detection of emamectin benzoate tolerance emergence in different life stages of sea lice, Lepeophtheirus salmonis, on farmed Atlantic salmon, Salmo salar L.

Emamectin benzoate has been used to treat sea lice, Lepeophtheirus salmonis, infestations on farmed Atlantic salmon, Salmo salar. Recent evidence suggests a reduction in effectiveness in some locations. A major challenge in the detection of tolerance emergence can be the typically low proportion of resistant individuals in a population during the early phases. The objectives of this study were to develop a method for determining differences in temporal development of tolerance between sea lice life stages and to explore how these differences might be used to improve the monitoring of treatment effectiveness in a clinical setting. This study examined two data sets based on records of sea lice abundance following emamectin benzoate treatments from the west coast of Scotland (2002-2006) and from New Brunswick, Canada (2004-2008). Life stages were categorized into two groups (adult females and the remaining mobile stages) to examine the trends in mean abundance and treatment effectiveness. Differences in emamectin benzoate effectiveness were found between the two groups by year and location, suggesting that an important part of monitoring drug resistance development in aquatic ectoparasites may be the need to focus on key life stages.

Dietary management of hepatic copper accumulation in Labrador Retrievers.

BACKGROUND: Copper-associated chronic hepatitis (CACH) recently has been recognized in the Labrador Retriever as an inherited disorder with a late onset of clinical signs. No studies have investigated dietary management for the long-term treatment of this disease or for its potential in delaying the onset of clinical signs in subclinical cases. OBJECTIVES: To investigate the effects of a low-copper diet and zinc gluconate on hepatic copper concentrations in Labrador Retrievers with abnormal hepatic copper concentrations. ANIMALS: Twenty-four client-owned Labradors that were related to patients affected with CACH and that had been diagnosed with increased hepatic copper concentrations. METHODS: Hepatic copper concentrations were assessed before and after an average of 8 and 16 months of treatment. During this time, all dogs were fed exclusively a low-copper diet. In addition, dogs were assigned to 1 of 2 groups in a randomized double-blind manner to receive a supplement of zinc gluconate or placebo. RESULTS: Twenty-one dogs completed the study. Hepatic copper concentrations decreased in both groups at recheck 1 (n = 21; group 1, P < .001; group 2, P= .001) and at recheck 2 (n= 16; group 1, P= .03; group 2, P= .04). No difference in hepatic copper concentrations was found between the 2 groups before treatment (P= .65), at recheck 1 or at recheck 2 (P= .52-.79). CONCLUSIONS AND CLINICAL RELEVANCE: Feeding low-copper diets to Labradors is effective in decreasing hepatic copper concentrations. Adjunctive treatment with zinc does not appear to increase the copper-lowering effects of dietary management.

Regulatory requirements for vaccine authorisation.

Vaccines are one of the most important tools available in the prevention and control of diseases in animals. It is therefore of the utmost importance that when vaccines are used, such use should meet with the requirements of the World Organisation for Animal Health Terrestrial Animal Health Code and must be authorised by the recognised licensing body in the country/region where the vaccines are to be used, in accordance with the three key criteria of quality, safety and efficacy. This article provides a comprehensive and comparative description of the regulatory requirements in place for veterinary vaccines in major regions of the world, highlighting the similarities and pointing out also where there are differences. Recent advances in harmonisation of such testing requirements achieved through the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) are also described. The contents will provide a valuable guide to those engaged in the research and development of vaccines globally, and reassure those involved in the prevention and control of animal diseases that veterinary vaccines, when fully authorised and used according to the label instructions, are safe and efficacious.

Species-specific in vitro pharmacological effects of the cannabinoid receptor 2 (CB2) selective ligand AM1241 and its resolved enantiomers.

BACKGROUND AND PURPOSE: Racemic (R,S) AM1241 is a cannabinoid receptor 2 (CB(2))-selective aminoalkylindole with antinociceptive efficacy in animal pain models. The purpose of our studies was to provide a characterization of R,S-AM1241 and its resolved enantiomers in vitro and in vivo. EXPERIMENTAL APPROACH: Competition binding assays were performed using membranes from cell lines expressing recombinant human, rat, and mouse CB(2) receptors. Inhibition of cAMP was assayed using intact CB(2)-expressing cells. A mouse model of visceral pain (para-phenylquinone, PPQ) and a rat model of acute inflammatory pain (carrageenan) were employed to characterize the compounds in vivo. KEY RESULTS: In cAMP inhibition assays, R,S-AM1241 was found to be an agonist at human CB(2), but an inverse agonist at rat and mouse CB(2) receptors. R-AM1241 bound with more than 40-fold higher affinity than S-AM1241, to all three CB(2) receptors and displayed a functional profile similar to that of the racemate. In contrast, S-AM1241 was an agonist at all three CB(2) receptors. In pain models, S-AM1241 was more efficacious than either R-AM1241 or the racemate. Antagonist blockade demonstrated that the in vivo effects of S-AM1241 were mediated by CB(2) receptors. CONCLUSIONS AND IMPLICATIONS: These findings constitute the first in vitro functional assessment of R,S-AM1241 at rodent CB(2) receptors and the first characterization of the AM1241 enantiomers in recombinant cell systems and in vivo. The greater antinociceptive efficacy of S-AM1241, the functional CB(2) agonist enantiomer of AM1241, is consistent with previous observations that CB(2) agonists are effective in relief of pain.

[Benzo[c][2,7]naphthyridine-5-yl-arylamines-phenol Mannich bases of the amodiaquine-, cycloquine- and pyronaridine-type]. / Benzo[c][2,7]naphthyridin-5-yl-arylamine-Phenol-Mannich-Basen vom Amodiaquin-, Cycloquin- und Pyronaridin-Typ.

2,5-Dichloro-4-methyl-benzo[c][2,7]naphthyridine (1) reacted with aromatic amines selectively by substitution at the 5-position to yield the amidines 2. The 4-aminophenol 2c could also be synthesized by cleavage of the ether 2b. The structure of 2c was proved by X-ray crystal analysis. Aminomethylation of 2c yielded the amodiaquine analogue 3. The mono- and bisaminomethylated derivatives 4 and 5 were obtained by reaction of compound 1 with phenol Mannich base hydrochlorides. Compounds 3-5 were tested in vitro for antimalarial activity using chloroquine-sensitive and resistant Plasmodium-falciparum strains. The highest activities were shown by the pyronaridine-type compounds 5a and 5b with IC50 values of approximately 200 nM.

[Benzo[c][2,7]naphthyridine-5-yl-amines and benzo[h][1,6]naphthyridine-5-yl-amines--potential antimalarials]. / Benzo[c][2,7]naphthyridin-5-yl-amine und Benzo[h][1,6]naphthyridin-5-yl-amine--Potenzielle Antimalariamittel.

The chloroimine 1a reacted with the novaldiamine-base to yield the 5-(2-methylpyrrolidinyl)-derivative 3. The 5-chloro-benzonaphthyridines 1 and 9 reacted with secondary aliphatic amines to give the amidines 5-8 and 10, while the aromatic amidines 11-14 were obtained with primary aromatic amines. Mixtures of the phenol Mannich bases 15 and 16 of the isoquine type were isolated from the aminomethylation of 13b. The amodiaquine analogues 19 and 20 were obtained from the reaction of 1b and 9a with 4-amino-2-piperidinomethyl-phenol dihydrochloride. The structure of the compounds 5a (potassium salt), 6b, 10a, 11e and 18 was proven by X-ray crystal analysis. Compounds 3, 6a-e, 7, 10a, 11a, 16, 19 and 20 were tested for in vitro antimalarial activity using a chloroquine-sensitive and -resistant Plasmodium falciparum strain. The highest activity against the sensitive strain was shown by the amodiaquine analogoue 20 with an IC50 value of 160 nM. The mixture of the isoquine derivatives 15a and 16a possessed the highest activity against the resistant strain with an IC50 value of 1100 nM.

Current availability of vaccines including vaccine banks.

Avian influenza can be considered one of the greatest global challenges the animal health sector has ever had to face. It is primarily a disease of animals and must be effectively managed by the veterinary community. Infection of humans in contact with the H5N1 virus continues to occur, however, with the possibility of mutations or re-assortment and the ever-present threat of the emergence of a pandemic. Therefore, whatever measures can be taken when outbreaks of avian influenza occur to reduce the amount of virus in circulation and potential human exposure must be reviewed constantly. Conventional methods for controlling diseases of epizootic proportions, such as avian influenza, have tended to rely on bio-security and culling (stamping out) of enormous numbers of animals. Such approaches might not be adequate in areas of intensive animal husbandry, and society is questioning more and more the ethics of slaughtering millions of animals. The costs and economic impact of this strategy also has a considerable effect on the economy of the country or region in which the disease outbreak occurs.

[Derivatives of exemestane--synthesis and evaluation of aromatase inhibition]. / Exemestan-derivate--Synthese und Prüfung auf Aromatase-Hemmung.

The irreversible aromatase inhibitor exemestane (6) reacts with nitromethane and sodium ethanolate to yield the Michael adduct 9. The aldehyde 10 is obtained by Nef reaction of the nitro compound 9 and affords the 1,4-dihydropyridine (DHP) 11 by Hantzsch reaction using methyl beta-aminocrotonate in acetic acid. The new compounds showed a reduced inhibitory potency towards aromatase (IC50 values: 9, 0.91 microM; 10, 2.5 microM; 11, 10 microM) compared to 6 (IC50 = 0.23 microM). The 1,4-DHP 11 was dehydrogenated with CAN or electrochemically (E1/2 =1.18 V) to yield the corresponding pyridine 12.

Resting energy expenditure and body composition of Labrador Retrievers fed high fat and low fat diets.

A high dietary fat intake may be an important environmental factor leading to obesity in some animals. The mechanism could be either an increase in caloric intake and/or a decrease in energy expenditure. To test the hypothesis that high fat diets result in decreased resting energy expenditure (REE), we measured REE using indirect calorimetry in 10-adult intact male Labrador Retrievers, eating weight-maintenance high-fat (HF, 41% energy, average daily intake: 8018 +/- 1247 kJ/day, mean +/- SD) and low-fat (LF, 14% energy, average daily intake: 7331 +/- 771 kJ/day) diets for a 30-day period. At the end of each dietary treatment, body composition measurements were performed using dual-energy X-ray absorptiometry. The mean +/- SD REE was not different between diets (4940 +/- 361 vs. 4861 +/- 413 kJ/day on HF and LF diets respectively). Measurements of fat-free mass (FFM) and fat mass (FM) also did not differ between diets (FFM: 26.8 +/- 2.3 kg vs. 26.3 +/- 2.5 kg; FM: 3.0 +/- 2.3 vs. 3.1 +/- 1.5 kg on HF and LF diets respectively). In summary, using a whole body calorimeter, we found no evidence of a decrease in REE or a change in body composition on a HF diet compared with LF diet.

[Contribution to the erythroquine and thalleioquine reaction]. / Zur Erythrochin- und Thalleiochin-Reaktion.

The 8,8'-biquinoline-5,5'-diones 2A are formed by the erythroquine and thalleioquine reaction from the 6-methoxyquinolines 1 as model compounds. The red substances 2A react with hydrochloric acid to yield the yellow biquinolinedihydrochlorides 3. The structure of 3b dihydrate is determined by X-ray crystal analysis. The redox properties of 2A are investigated by voltammetric methods.

[Annulated heterocycles from methyl 6-chloro-5-formyl-2-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate]. / Anellierte Heterocyclen aus 6-chlor-5-formyl-2-methyl-4-(2-nitrophenyl)-1,4- dihydropyridin-3-carbonsäuremethylester.

The pyridone 1a reacts with POCl3/DMF to yield the title compound 2a. After irradiation of 2a the enolether 3 is isolated, as shown by an X-ray structure determination. The pyridine 4 obtained by dehydrogenation of 2a leads under reductive conditions to the benzo[c][2,7]naphthyridines 5-7. The reaction of 4 with o-phenylenediamine gives the benzimidazole 8, while using 2-aminophenol or 2-aminothiophene respectively the pyrido[2,3-b[1,5]benzoxazepine 11 and the corresponding benzothiazepine 12 are obtained.

[Benzo[c][2,7]naphthyridine-2-yl-, 5-yl- and 2,5-diyl novaldiamines--synthesis and investigation of anti-malarial activity]. / Benzo[c][2,7]naphthyridin-2-yl-, 5-yl- und 2,5-diyl-novaldiamine--synthese und prüfung auf wirksamkeit gegen Malaria.

The 2,5-dichlorobenzo[c][2,7]naphthyridine 6 was synthesized starting from the 2-pyridone 1 in four or five steps, respectively. The 5-yl amine 7 and the 2,5-diyl amines 8 and 9 were isolated by the reaction of compound 6 with the novaldiamine base. Starting with the reaction of the 6-chloropyridine 3 with the novaldiamine base to yield the 6-aminopyridine 11, the 2-yl amine 13, isomeric to 7, was obtained. Compounds 7-13 were tested for in vitro antimalarial activity using a chloroquine sensitive and resistant Plasmodium falciparum strain. The highest activity was shown by 8 with IC50 values of 90 nM and 190 nM, respectively.

High-resolution characterization of the canine DLA-DRB1 locus using reference strand-mediated conformational analysis.

Several methods exist for genotyping class II DLA gene polymorphisms in the dog. The most accurate method is sequence-based typing, which involves direct sequencing of polymerase chain reaction products. However, this method is expensive and unsuitable for large-scale studies. Recently, reference strand-mediated conformation analysis (RSCA) has been shown to be effective for characterizing major histocompatibility complex genes in humans, sheep, horse, and cats. RSCA is a cheap and rapid method, ideal for large epidemiological studies. We have developed RSCA for typing DLA-DRB1 in the dog. Control panels including dogs typed by sequence-based typing and cloned major histocompatibility complex class II alleles in plasmids were used to establish migration patterns for each allele using 20 different fluorescent labeled references, of which 5 were selected to allow for clear identification and discrimination of all known DLA-DRB1 alleles. We have compared 168 dogs typed by RSCA for DLA-DRB1 and characterized by sequence-based typing, with less than 1% discrepancy. These differences were due to missing alleles because of a weak polymerase chain reaction. To date, we have RSCA-typed 1,394 dogs. RSCA is likely to become the method of choice for characterizing DLA genes in the dog and will prove a useful tool for dissecting the immune response of dogs in clinical studies.

[Biphenyl derivatives as by-products from the synthesis of 4-aryl-4H-pyrans]. / Biphenyl-derivate als nebenprodukte der synthese von 4-aryl-4H-pyranen.

The reaction of the 1,5-diketones 1 with acetic anhydride/acetic acid in the presence of zinc chloride yields the 4-aryl-4H-pyrans 2 as main products. The annulated lactone 3 and the cyclohexene derivatives 5 are isolated as by-products. The configuration of the cyclohexanone 4a and the cyclohexenes 5 are deduced from nmr spectroscopic methods. The structure of 5b is confirmed by X-ray crystal analysis.

[12-acyl-6,1 2-dihydro-6-phenyl-[1 ]benzofuro[2,3-c]- and -[1,5]benzothieno[2,3-c]-[1 ,5]-benzothiazepines--tetracyclic diltiazem derivatives]. / 12-Acyl-6,12-dihydro-6-phenyl-[1]benzofuro[2,3-c]- und -[1]benzothieno-[2,3-c]-[1,5]benzothiazepine--tetracyclische Diltiazem-Derivate.

The reaction of the tetracycles 1 with chloroacetylchloride yields the amides 2. The structure of 2a was proven by X-ray analysis. The amides 2 exist as diastereomers in solution because of planar chirality. From the N-chloroacetyl compounds only 2a, b could be substituted with diethylamine to give 3a, b. Reduction experiments of 3a, b with DIBAH do not afford diltiazem analogues; instead, the starting compounds la, b are formed by hydrolysis.

[Color reaction of chlorhexidine and proguanil with hypobromite]. / Zur Farbreaktion von Chlorhexidin und Proguanil mit Hypobromit.

Colour reaction of chlorhexidine and proguanil with hypobromite The antimalarial agent proguanil reacts with hypobromite to yield the red coloured (E)-3-[(4-chlorophenyl)imino]-N-isopropyl-3H-1,2,4-triazol-5-amine (6B). The structure of 6B was proven by X-ray. The red colour obtained by the test for the disinfectant chlorhexidinedihydrochloride Ph. Eur. with hypobromite is probably attributable to a corresponding chromophore.