Type 2 diabetes is associated with the accumulation of senescent T cells.

Type 2 diabetes is a global health priority, given that it is driven, in part, by an ageing population, the role of immune senescence has been overlooked. This is surprising, as the functional impairments of senescent T cells show strong similarities to patients with hyperglycaemia. Immune senescence is typified by alterations in T cell memory, such as the accumulation of highly differentiated end-stage memory T cells, as well as a constitutive low-grade inflammation, which drives further immune differentiation. We show here in a preliminary study that people living with type 2 diabetes have a higher circulating volume of senescent T cells accompanied with a higher level of systemic inflammation. This inflammatory environment drives the expression of a unique array of chemokine receptors on senescent T cells, most notably C-X-C motif chemokine receptor type 2. However, this increased expression of migratory markers does not translate to improved extravasation owing to a lack of glucose uptake by the T cells. Our results therefore demonstrate that the presence of senescent T cells has a detrimental impact on immune function during type 2 diabetes.

Histories of host shifts and cospeciation among free-living parasitoids of Rhagoletis flies.

Host shifts by specialist insects can lead to reproductive isolation between insect populations that use different hosts, promoting diversification. When both a phytophagous insect and its ancestrally associated parasitoid shift to the same novel host plant, they may cospeciate. However, because adult parasitoids are free living, they can also colonize novel host insects and diversify independent of their ancestral host insect. Although shifts of parasitoids to new insect hosts have been documented in ecological time, the long-term importance of such shifts to parasitoid diversity has not been evaluated. We used a genus of flies with a history of speciation via host shifting (Rhagoletis [Diptera: Tephritidae]) and three associated hymenopteran parasitoid genera (Diachasma, Coptera and Utetes) to examine cophylogenetic relationships between parasitoids and their host insects. We inferred phylogenies of Rhagoletis, Diachasma, Coptera and Utetes and used distance-based cophylogenetic methods (ParaFit and PACo) to assess congruence between fly and parasitoid trees. We used an event-based method with a free-living parasitoid cost model to reconstruct cophylogenetic histories of each parasitoid genus and Rhagoletis. We found that the current species diversity and host-parasitoid associations between the Rhagoletis flies and parasitoids are the primary result of ancient cospeciation events. Parasitoid shifts to ancestrally unrelated hosts primarily occur near the branch tips, suggesting that host shifts contribute to recent parasitoid species diversity but that these lineages may not persist over longer time periods. Our analyses also stress the importance of biologically informed cost models when investigating the coevolutionary histories of hosts and free-living parasitoids.

Appropriateness of acute-care antibiotic prescriptions for community-acquired infections and surgical antibiotic prophylaxis in England: analysis of 2016 national point prevalence survey data.

BACKGROUND: Estimates of inappropriate prescribing can highlight key target areas for antimicrobial stewardship (AMS) and inform national targets. OBJECTIVES: To (1) define and (2) produce estimates of inappropriate antibiotic prescribing levels within acute hospital trusts in England. METHODS: The 2016 national Healthcare-Associated Infections (HAI), Antimicrobial Use (AMU) and AMS point prevalence survey (PPS) was used to derive estimates of inappropriate prescribing, focusing on the four most reported community-acquired antibiotic indications (CAIs) in the PPS and surgical prophylaxis. Definitions of appropriate antibiotic therapy for each indication were developed through the compilation of national treatment guidelines. A Likert-scale system of appropriateness coding was validated and refined through a two-stage expert review process. RESULTS: Antimicrobial usage prevalence data were collected for 25,741 individual antibiotic prescriptions, representing 17,884 patients and 213 hospitals in England. 30.4% of prescriptions for the four CAIs of interest were estimated to be inappropriate (2054 prescriptions). The highest percentage of inappropriate prescribing occurred in uncomplicated cystitis prescriptions (62.5%), followed by bronchitis (48%). For surgical prophylaxis, 30.8% of prescriptions were inappropriate in terms of dose number, and 21.3% in terms of excess prophylaxis duration. CONCLUSIONS: The 2016 prevalence of inappropriate antibiotic prescribing in hospitals in England was approximated to be 30.4%; this establishes a baseline prevalence and provided indication of where AMS interventions should be prioritized. Our definitions appraised antibiotic choice, treatment duration and dose number (surgical prophylaxis only); however, they did not consider other aspects of appropriateness, such as combination therapy - this is an important area for future work.

Alternative methods for computing the sensitivity of complex surveillance systems.

Stochastic scenario trees are a new and popular method by which surveillance systems can be analyzed to demonstrate freedom from pests and disease. For multiple component systems-such as a combination of a serological survey and systematically collected observations-it can be difficult to represent the complete system in a tree because many branches are required to represent complex conditional relationships. Here we show that many of the branches of some scenario trees have identical outcomes and are therefore redundant. We demonstrate how to prune branches and derive compact representations of scenario trees using matrix algebra and Bayesian belief networks. The Bayesian network representation is particularly useful for calculation and exposition. It therefore provides a firm basis for arguing disease freedom in international forums.

Mortality among tuberculosis patients in New York City.

OBJECTIVES: To quantify tuberculosis (TB) related mortality among TB patients in New York City (NYC), NY, USA, and identify risk factors associated with TB-related mortality. DESIGN: We performed a retrospective analysis of verified TB patients in NYC, 2004-2013. NYC Office of Vital Statistics death certificate data and TB surveillance data were matched. Death certificate data were used to identify TB-related deaths. Risk factors for TB-related death for US-born and non-US-born populations were evaluated using multivariable logistic regression. RESULTS: Of 8209 TB patients in NYC, 168 (2%) suffered TB-related deaths before or during anti-tuberculosis treatment. Of these, 62% occurred among non-US-born patients, and 38% occurred among US-born patients. Among the latter, TB-related death was associated with increased age (65 vs. 18-44 years, adjusted OR [aOR] 8.27, 95%CI 3.47-19.71), being culture-positive (aOR 6.79, 95%CI 2.10-21.97), and having both pulmonary and extra-pulmonary disease (aOR 5.06, 95%CI 1.91-13.40). The same factors were also significant among non-US-born patients; TB-related death was also associated with male sex (aOR 1.80, 95%CI 1.11-2.91), history of TB disease (aOR 3.16, 95%CI 1.28-7.77), alcohol use (aOR 1.85, 95%CI 1.00-3.43), homelessness (aOR 2.66 95%CI 1.15-6.19), and unknown human immunodeficiency virus status (aOR 3.91, 95%CI 2.43-6.29). CONCLUSION: Different risk factors between the US- and non-US-born populations were identified. Interventions specific to each population may be needed for reducing TB-related mortality.

Trophectoderm in control of murine embryonal carcinoma.

It has been shown previously that the intact blastocyst of the mouse can regulate tumor formation and colony formation of murine embryonal carcinoma. This effect is consistent with the close histogenetic correspondence between embryonal carcinoma and the inner cell mass of the blastocyst. The ability of inner cell mass, blastocele fluid, and inner and outer surfaces of trophectoderm to abrogate colony formation of a variety of malignant tumors has now been tested. Direct contact of the embryonal carcinoma cells with the blastocele surface of trophectoderm proved to be necessary for abrogation of colony formation of embryonal carcinoma. This effect was not seen with any of the other tumors tested. Some tumors, which lack a normal cellular counterpart in the blastocyst, grew poorly in the blastocele unless a fistula was made in the wall of the blastocyst. Colony formation of the embryonal carcinoma was regulated in blastocysts with fistulas, but the other tumors were not regulated under these conditions. It is concluded that colony formation of embryonal carcinoma cells is regulated by direct contact with the trophectoderm of its corresponding embryonic field in an unknown but specific manner.

Overexpression of Ephrin A3 Receptor in Canine Prostatic Carcinoma.

Ephrin A3 (EphA3), a member of the ephrin receptor tyrosine kinase family, is involved in a variety of functions in normal cells, especially during embryonic development, and alterations in its expression profile have been observed in several human cancers. However, there are no reports of the expression of EphA3 in normal, hyperplastic or neoplastic canine prostate tissue or in other types of canine tumours. Six normal, 15 hyperplastic and 21 neoplastic canine prostates were examined immunohistochemically with a polyclonal antibody specific for human EphA3. The percentage of positive cells in all prostatic carcinomas was increased, with a mean of 89.28 ± 5.18% compared with normal (9.17 ± 6.72%) and hyperplastic prostates (20.00 ± 8.28%). EphA3 expression was not correlated with the histological subtypes of prostate cancer or with the Gleason score. The increase in EphA3 expression in canine prostatic carcinomas suggests the involvement of this receptor in prostatic carcinogenesis and its potential use as a target for new therapeutic strategies.

Can foxes be controlled by reducing their fertility?

A model based on data from research in New South Wales conducted by the Cooperative Research Centre for the Biological Control of Vertebrate Pest Populations suggests that the effectiveness of fertility control in reducing the abundance of foxes (Vulpes vulpes) can be strongly influenced by environmental variability. The model includes age-specific recruitment and survival as functions of resources indexed by rainfall. It is assumed that fertility control will affect only female foxes and that the use of a baiting regime to deliver a contraceptive agent will result in fixed proportional changes in pregnancy rates. By comparing the variability in the rate of increase of treated and untreated fox populations, the model predicts that: (i) frequent baiting, every one or two years, will be more effective than applications of baits at longer time intervals; (ii) the abundance of foxes will decline more rapidly, with higher levels of fertility control; (iii) infertility which lasts for only one breeding season is less effective than permanent sterility which allows for accumulation of sterile animals in the population; and (iv) highly variable results are likely to be the outcome of low-frequency baiting with an agent that produces only temporary infertility.

Arthroscopy under local anaesthesia.

Sixty patients underwent arthroscopy of the knee as day cases using a local anaesthetic technique. This provided satisfactory operating conditions and high patient acceptability.

Difficult intubation following thoracic trauma.

A previously fit 20-year-old man presented with a large haemothorax following a stab wound to the left chest. Pre-operative airway assessment indicated that tracheal intubation would be routine. On induction of anaesthesia, visualisation of the larynx proved impossible because of soft tissue swelling. Successful intubation was eventually achieved with the aid of a gum elastic bougie. At operation, the patient's common carotid artery was found to have been perforated close to its origin on the aorta. The patient made an uneventful recovery.

Long-term implantation of gentamicin-polymethylmethacrylate antibiotic beads.

Fifty-two chronic osteomyelitis patients treated with gentamicin-polymethylmethacrylate (Septopal) antibiotic bead chains were observed retrospectively to explore the relationship between the duration of bead implantation and clinical results. Group A contained 35 asymptomatic patients who had elective bead removal based on protocol, surgeon's preference, and patient variables. Group B consisted of 17 patients who retained the antibiotic beads. The presence or absence of redness, abscess, drainage, pain, or swelling at the wound site was documented for clinical evaluation. Findings indicate that Septopal bead chain implants exhibit higher success (remission) rates with increasing length of duration without increasing the risk of complications.

Postoperative analgesia after triple nerve block for fractured neck of femur.

Fifty patients with fractured neck of femur that required surgical correction with either a compression screw or pin and plate device were randomly allocated to receive one of two anaesthetic techniques, general anaesthesia combined with either opioid supplementation or triple nerve block (three in one block) with subcostal nerve block. The nerve blocks significantly reduced the quantity of opioid administered after operation; 48% of these patients required no additional analgesia in the first 24 hours. Plasma prilocaine levels in these patients were well below the toxic threshold, and peak absorption occurred 20 minutes after the injection. No untoward sequelae were associated with the nerve blocks.

Ribosomal protein RL44 is encoded by two subfamilies in upland cotton (Gossypium hirsutum L.).

We have isolated 4 cDNA clones encoding the full-length sequence of the eukaryotic ribosomal protein RL44 from upland cotton (Gossypium hirsutum L.). Sequencing of these clones resulted in the classification of 2 subfamilies of RL44; these subfamilies had coding regions (315 bp) which were 92% identical. RL44-1 (454 bp) and RL44-2 (485 bp) constitute subfamily 1, whereas RL44-3 (913 bp) and RL44-5 (541 bp) constitute subfamily 2. The differences in nucleotide sequences, however, occurred only at third codon positions and the resulting amino acid sequences of the two RL44 subfamilies were identical. The ORF encoded a protein of 105 residues with a Mr = 12029. A bipartite nuclear targeting sequence was identified from residues 29 to 43.

Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales, Australia. II. Selection of a strain of virus for release.

To be able to study the dynamics of myxoma virus spread following a release in the field, a strain of virus is required that is both highly transmissible and readily differentiated from other field strains. Eight strains of virus of known virulence for laboratory rabbits and with previously mapped and sequenced restriction fragment length polymorphisms, were used to infect groups of seronegative wild rabbits. Based on these trials, and on the nature of the DNA polymorphism, a virus designated Brooklands/2-93 was chosen as a strain suitable for experimental release. These trials confirmed that resistance to myxomatosis within wild rabbit populations continues to be substantial and that some rabbits are highly resistant. These rabbits probably have little role in transmission of virus. Most of the virus strains tested induced very small or invisible primary lesions at the inoculation site. Thus the secondary skin sites such as eyelids, face and ears may be critical for transmission.

Diabetes services in the UK: third national survey confirms continuing deficiencies.

AIMS: To determine the current level of diabetes services and to compare the results with previous national surveys. METHODS: A questionnaire was mailed to all paediatricians in the UK identified as providing care for children with diabetes aged under 16 years. Information was sought on staffing, personnel, clinic size, facilities, and patterns of care. Responses were compared with results of two previous national surveys. RESULTS: Replies were received from 244 consultant paediatricians caring for an estimated 17 192 children. A further 2234 children were identified as being cared for by other consultants who did not contribute to the survey. Of 244 consultants, 78% expressed a special interest in diabetes and 91% saw children in a designated diabetic clinic. In 93% of the clinics there was a specialist nurse (44% were not trained to care for children; 47% had nurse:patient ratio >1:100), 65% a paediatric dietitian, and in 25% some form of specialist psychology or counselling available. Glycated haemoglobin was measured routinely at clinics in 88%, retinopathy screening was performed in 87%, and microalbuminuria measured in 66%. Only 34% consultants used a computer database. There were significant differences between the services provided by paediatricians expressing a special interest in diabetes compared with "non-specialists", the latter describing less frequent clinic attendance of dietitians or psychologists, less usage of glycated haemoglobin measurements, and less screening for vascular complications. Non-specialist clinics met significantly fewer of the recommendations of good practice described by Diabetes UK. CONCLUSIONS: The survey shows improvements in services provided for children with diabetes, but serious deficiencies remain. There is a shortage of diabetes specialist nurses trained to care for children and paediatric dietitians, and a major shortfall in the provision of psychology/counselling services. The services described confirm the need for more consultant paediatricians to receive specialist training and to develop expertise and experience in childhood diabetes.