Antimicrobial prophylaxis in companion animal surgery: A scoping review for European Network for Optimization of Antimicrobial Therapy (ENOVAT) guidelines.

Surgical antimicrobial prophylaxis (SAP) is widely used to reduce the risk of surgical site infections (SSI), but there is uncertainty as to what the proportion of SSI reduction is. Therefore, it is difficult for surgeons to properly weigh the costs, risks and benefits for individual patients when deciding on the use of SAP, making it challenging to promote antimicrobial stewardship in primary practice settings. The objective of this study was to map the veterinary evidence focused on assessing the effect of SAP on SSI development and in order to identify surgical procedures with some research evidence and possible knowledge gaps. In October 2021 and December 2022, Scopus, CAB Abstracts, Web of Science Core Collection, Embase and MEDLINE were systematically searched. Double blinded screening of records was performed to identify studies in companion animals that reported on the use of SAP and SSI rates. Comparative data were available from 34 out of 39123 records screened including: eight randomised controlled trials (RCT), 23 cohort studies (seven prospective and 16 retrospective) and three retrospective case series representing 12476 dogs and cats in total. Extracted data described peri- or post-operative SAP in nine, and 25 studies, respectively. In the eight RCTs evaluating SAP in companion animals, surgical procedure coverage was skewed towards orthopaedic stifle surgeries in referral settings and there was large variation in SAP protocols, SSI definitions and follow-up periods. More standardized data collection and agreement of SSI definitions is needed to build stronger evidence for optimized patient care.

Short-term outcome and complications following cutaneous reconstruction using cranial superficial epigastric axial pattern flaps in dogs: six cases (2008-2022).

OBJECTIVES: To investigate short-term outcome and complications following the use of the cranial superficial epigastric axial pattern flap to reconstruct cutaneous defects in dogs. MATERIALS AND METHODS: Medical records from dogs undergoing reconstructive surgery between 2008 and 2022 by means of cranial superficial epigastric axial pattern flap were reviewed. Data on signalment, reason for reconstruction, defect size, flap healing, post-operative complications and need for revision surgery were collected. RESULTS: Six dogs were included in the study. Indications for reconstruction included neoplasia (4/6), skin necrosis due to vehicular trauma (1/6) and dog bite (1/6). Postoperative complications occurred in 50% of the patients and included seroma (1/6), bruising (2/6) and necrosis of the distal portion of the flap (2/6), with two dogs developing concurrent complications. One dog required open wound management and additional surgery. Overall outcome was scored excellent in three, good in two, and fair in one dog. CLINICAL SIGNIFICANCE: Despite the relatively high complication rate, most of the complications were deemed minor and could be managed conservatively. Eventually, all wounds healed completely and only one flap required revision surgery.

Endoscopic treatment of acute oropharyngeal stick injuries in dogs: 46 cases (2010-2020).

OBJECTIVES: To review long-term outcomes of dogs with acute oropharyngeal stick injuries managed with rigid endoscopy at a UK referral centre. MATERIALS AND METHODS: Retrospective analysis and follow-up with referring veterinary surgeons and owners of patients treated between 2010 and 2020. A medical record search was performed and data regarding signalment, clinical presentation, treatment and long-term outcomes were recorded. RESULTS: Sixty-six dogs with acute oropharyngeal stick injury were identified and 46 (70.0%) of these had endoscopy of the wound. The dogs were of various breeds, ages (median=3 years; range 0.6 to 11 years) and weights (median=20.4 kg; range 7.7 to 38.4 kg) and 58.7% of patients were male. The median time from injury to referral was 1 day (range 2 hours to 7 days). Patients were anaesthetised, and injury tracts were explored using 0° and 30° forward-oblique, 2.7 mm diameter, 18 cm length rigid endoscopes with a corresponding 14.5 French sheath using saline infusion via gravity. All foreign material that could be grasped was removed using forceps. Tracts were flushed with saline and reinspected to confirm removal of all visible foreign material. Out of 40 dogs with long-term follow-up, 38 (95.0%) had no major long-term complications. The remaining two dogs developed cervical abscessation after endoscopy, one of which resolved after repeat endoscopy and the other resolved after open surgery. CLINICAL SIGNIFICANCE: Long-term follow-up of dogs with acute oropharyngeal stick injury managed with rigid endoscopy showed an excellent outcome in 95.0% of cases.

Culinary Nutrition Education Programs in Community-Dwelling Older Adults: A Scoping Review.

BACKGROUND: Culinary nutrition education programs are increasingly used as a public health intervention for older adults. These programs often integrate nutrition education in addition to interactive cooking workshops or displays to create programs suitable for older adults' needs, ability and behaviour change. Synthesising the existing literature on nutrition education and interactive cooking programs for older adults is important to guide future program development to support healthy ageing. OBJECTIVES: To determine the extent of published literature and report the characteristics and outcomes of interactive culinary nutrition education programs for older adults (> 51 years). DESIGN: This scoping review followed the PRISMA-ScR guidelines recommended for reporting and conducting a scoping review. METHODS: Five databases were searched of relevant papers published to May 2022 using a structured search strategy. Inclusion criteria included: older adults (≥ 51 years), intervention had both an interactive culinary element and nutrition education and reported dietary outcome. Titles and abstracts were screened by two reviewers, followed by full-text retrieval. Data were charted regarding the characteristics of the program and outcomes assessed. RESULTS: A total of 39 articles met the full inclusion criteria. The majority of these studies (n= 23) were inclusive of a range of age groups where older adults were the majority but did not target older adults exclusively. There were large variations in the design of the programs such as the number of classes (1 to 20), duration of programs (2 weeks to 2 years), session topics, and whether a theoretical model was used or not and which model. All programs were face-to-face (n= 39) with only two programs including alternatives or additional delivery approaches beside face-to-face settings. The most common outcomes assessed were dietary behaviour, dietary intake and anthropometrics. CONCLUSION: Culinary nutrition education programs provide an environment to improve dietary habits and health literacy of older adults. However, our review found that only a small number of programs were intentionally designed for older adults. This review provides a summary to inform researchers and policy makers on current culinary nutrition education programs for older adults. It also recommends providing face-to-face alternatives that will be accessible to a wider group of older adults with fewer restrictions.

Description and outcome of dogs with primary immune-mediated polyarthritis: 73 cases (2012-2017).

OBJECTIVES: To provide a description of primary idiopathic immune-mediated polyarthritis, including long-term outcome and relapse rates, for dogs starting treatment with corticosteroids alone or corticosteroids with a second immunosuppressant. MATERIALS AND METHODS: Medical records were reviewed between January 2012 and December 2017 to identify dogs diagnosed with primary immune-mediated polyarthritis. Data including signalment, clinicopathological findings, type and duration of treatment, relapse and outcome were recorded. RESULTS: Seventy-three dogs were included. Fifty-four dogs were started on corticosteroid monotherapy (an additional immunosuppressant was introduced later in 27/54 dogs) and 19 dogs were treated with multi-modal immunosuppression from the outset. Ninety-five percent (69/73) of dogs responded favourably to therapy although death was attributed to immune-mediated polyarthritis in 19% (14/73) of dogs. Relapse of clinical signs was reported in 53% (39/73) dogs (31/39 while on treatment), with multiple relapses observed in 17 dogs. Complete cure (permanent withdrawal of immunosuppressive medication) was achieved in 46 dogs (63%). Overall, 81% of dogs had a well-managed disease for an extended timeframe (≥1131 days). Fourteen of 19 (74%) dogs that started treatment with multi-modal immunosuppression and 32 of 54 (59%) started on corticosteroids alone achieved a complete cure. CLINICAL SIGNIFICANCE: This study provides extended follow-up information for a large cohort of dogs with primary immune-mediated polyarthritis. Immunosuppressive therapy was discontinued in the majority of dogs but disease-associated mortality remains high.

Outcome of caudal superficial epigastric axial pattern flaps in dogs and cats: 70 cases (2007-2020).

OBJECTIVES: To describe the outcome and complications associated with the use of caudal superficial epigastric axial pattern flaps in dogs and cats. MATERIAL AND METHODS: Multicentre retrospective review and descriptive study of clinical records of dogs and cats having undergone caudal superficial epigastric axial pattern flaps between 2007 and 2020. Data retrieved included signalment, aetiology of surgical defect, tumour type, presence/absence of clean surgical margins, presence/absence of post-operative wound infection, use of peri- and post-operative antibiotics, duration of anaesthesia, duration of surgery, presence and duration of hypothermia, presence and duration of hypotension, presence/absence of post-operative surgical drain and length of caudal superficial epigastric axial pattern flap. The incidence of complications and outcomes were documented. RESULTS: Seventy cases met the inclusion criteria; 51 dogs and 19 cats. In dogs, 67% of cases developed complications (59% minor, 8% major) and 33% had uneventful wound healing. In cats, 53% of cases developed complications, (47% minor, 5% major) and 47% had uneventful wound healing. In dogs, the percentage of cases experiencing dehiscence, necrosis, seroma, oedema and post-operative infection was 31%, 29%, 26%, 26% and 16% respectively. In cats, this was 26%, 16%, 11%, 0% and 5% respectively. A good overall outcome was seen in 77% of dogs and 79% of cats. A poor overall outcome was seen in 4% of dogs and 0% of cats. CLINICAL SIGNIFICANCE: Caudal superficial epigastric axial pattern flaps are traditionally thought more robust than other flaps, yet complication rates remain high, despite a high overall success rate.

Outcome of superficial brachial axial pattern flaps used to close skin defects in dogs: 16 cases (1996-2019).

OBJECTIVES: To report the complication rate, type of complications and outcome of the superficial brachial axial pattern flap when used for closure of skin defects in dogs. MATERIALS AND METHODS: Medical records of dogs treated with a superficial brachial axial pattern flap for closure of a skin defect were reviewed. Information regarding signalment, reason for axial pattern flap use, skin flap size, flap healing, postoperative complications and need for revision surgery was collected. RESULTS: Sixteen dogs were included in the study. Indications for the superficial brachial axial pattern flap included closure following tumour removal (15/16, 94%) and management of a non-healing wound on the olecranon (1/16, 6%). Postoperative complications occurred in all dogs and included partial dehiscence (7/16, 44%), partial flap necrosis (6/16. 38%), seroma formation (5/16, 31%), flap oedema (3/16, 19%) and complete flap necrosis (2/16, 13%). Eight flaps (50%) healed without open wound management or additional surgery. Five dogs required open wound management without additional surgery, and three dogs (19%) required revision surgery. CLINICAL SIGNIFICANCE: Use of the superficial brachial axial pattern flap was associated with a high rate of complications. Most complications were managed without additional surgery and all wounds eventually healed, in some cases after prolonged open wound management.

Superficial temporal axial pattern flap for facial reconstruction of skin defects in dogs and cats.

OBJECTIVES: Report the use, complications and outcome of the superficial temporal axial pattern flap (STA) when used for closure of skin defects localised to the maxillofacial region in dogs and cats. MATERIALS AND METHODS: Multi-centre retrospective cohort study. Medical records of dogs and cats treated with a STA flap for closure of skin defects were reviewed. Information regarding signalment, reason for axial pattern flap use, flap size, flap healing, postoperative complications including need for surgical revision and overall outcome were collected. RESULTS: Nineteen patients were included: nine dogs and 10 cats. Indications for the STA flap included closure of defects following excision of tumours (18/19, 94.7%) and fungal granuloma resection (1/19, 5.2%). 100% flap survival occurred in 17 of 19 flaps (89.4%). Postoperative complications occurred in eight of 19 flaps (42.1%). A major complication of full thickness partial necrosis of the flap occurred in one of 19 cases (5.2%), where the flap length exceeded recommended guidelines. Minor complications related to the flap were seen in four of 19 cases (21%). This included partial thickness flap necrosis, flap oedema and wound discharge. Complications related to the location of surgery (5/19, 26.3%) included mild ectropion, mild exposure of the eye, reduced ability to blink and subcutaneous emphysema. CLINICAL SIGNIFICANCE: The STA flap is a good option for closure of a skin defect localised to the maxillofacial region. STA flaps were associated with a high percentage of survival and a low incidence of major complications.

Atypical lateral tracheal collapse in a Yorkshire terrier.

A 10-month-old, neutered female Yorkshire terrier was presented with a 6-month history of inspiratory dyspnoea, coughing and exercise intolerance. Tracheoscopy revealed marked lateral-to-lateral fixed collapse of the cervical trachea and mild collapse of the thoracic trachea. Surgical exploration revealed a marked reduction in lateral tracheal width and multiple malformed tracheal rings. Placement of extraluminal ring prostheses around the cervical trachea resulted in widening of the tracheal diameter and an immediate improvement in clinical signs. 6 years postoperatively the patient was reported to have an excellent quality of life with complete resolution of clinical signs.

Magnetic Monopole Search with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions Interpreted in Photon-Fusion and Drell-Yan Production.

MoEDAL is designed to identify new physics in the form of stable or pseudostable highly ionizing particles produced in high-energy Large Hadron Collider (LHC) collisions. Here we update our previous search for magnetic monopoles in Run 2 using the full trapping detector with almost four times more material and almost twice more integrated luminosity. For the first time at the LHC, the data were interpreted in terms of photon-fusion monopole direct production in addition to the Drell-Yan-like mechanism. The MoEDAL trapping detector, consisting of 794 kg of aluminum samples installed in the forward and lateral regions, was exposed to 4.0 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges equal to or above the Dirac charge are excluded in all samples. Monopole spins 0, ½, and 1 are considered and both velocity-independent and-dependent couplings are assumed. This search provides the best current laboratory constraints for monopoles with magnetic charges ranging from two to five times the Dirac charge.

A Retrospective Study of Multi-agent Chemotherapy including either Cyclophosphamide or Lomustine as Initial Therapy for Canine High-grade T-cell Lymphoma (2011-2017).

Multi-agent chemotherapy (vincristine, epirubicin and prednisolone) including either cyclophosphamide (CEOP) or lomustine (LEOP) was given as first-line chemotherapy to treatment-naïve canine lymphoma patients with measurable, high grade T-cell lymphoma (HGTCL). All patients responded to either CEOP or LEOP. Toxicity was typical of multi-agent chemotherapy protocols and 25% of dogs receiving lomustine exhibited mild-to-moderate ALT elevation and 29% grade 3 or 4 neutropenia. Median progression-free survival (100 versus 269 days) and overall survival (155 versus 327 days) were significantly higher in patients receiving LEOP compared to CEOP. Overall survival was improved for patients receiving LEOP compared to those receiving CEOP followed by lomustine-based rescue therapy. The results of this retrospective study support further evaluation of lomustine as part of first-line, multi-agent therapy for patients with HGTCL.

A laboratory-based evaluation of tube blocking and microbial risks associated with one blended enteral feed recipe.

BACKGROUND: Concerns associated with blended enteral feeds include the risk of blocked tubes and microbial contamination, although the available evidence is limited. The present laboratory-based investigation aimed to examine these risks in a blended feed providing a nutritionally adequate intake for a hypothetical patient. METHODS: A one-blended feed recipe was made using three different methods (professional, jug and stick blenders) and three storage procedures. Feed samples were syringed via 10-, 12- and 14-French (Fr) enteral feeding tubes and both blockages and the time taken were recorded. Feed samples were diluted, plated on agars, incubated and bacterial colony-forming units (CFU) counted. After storage at -80 °C, identification was undertaken using 16S rRNA polymerase chain reaction sequencing. RESULTS: Two blockages occurred during 27 administrations of feed made using a professional blender, although they were resolved with a water flush. No blockages occurred with the 14-Fr tube and administration was quicker with wider tubes (P < 0.00001). There was no significant difference between the total bacterial CFU of feeds prepared using different methods (P = 0.771) or stored differently. The genus of bacteria identified included Enterococcus, Bacillus, lactose-fermenting Enterobacteriaceae, Pseudomonas and Staphylococcus. Pathogens, such as Clostridium spp., Salmonella spp. and Vibrio spp., were not identified by phenotypic tests used. Sequencing identified Escherichia coli, Shigella spp., Streptococcus lutetiensis and Staphylococcus epidermidis. CONCLUSIONS: The present study found no risk of tube blockages when one blended feed recipe made using three methods was delivered via a 14-Fr tube. There is concern about bacterial contamination, although this was not influenced by the methods of preparation or storage used in the present study.

Probiotics in Goat Milk Products: Delivery Capacity and Ability to Improve Sensory Attributes.

Dairy foods, particularly those of bovine origin, are the predominant vehicles for delivery of probiotic bacteria. Caprine (goat) milk also possesses potential for successful delivery of probiotics, and despite its less appealing flavor in some products, the use of goat milk as a probiotic carrier has rapidly increased over the last decade. This review reports on the diversity, applicability, and potential of using probiotics to enhance the sensory properties of goat milk and goat milk-based products. A brief conceptual introduction to probiotic microorganisms is followed by an account of the unique physicochemical, nutritive, and beneficial aspects of goat milk, emphasizing its advantages as a probiotic carrier. The sensory properties of probiotic-enriched goat milk products are also discussed. The maintenance of probiotic viability and desirable physicochemical characteristics in goat milk products over shelf life is possible. However, the unpleasant sensory features of some goat milk products remain a major disadvantage that hinder its wider utilization. Nevertheless, certain measures such as fortification with selected probiotic strains, inclusion of fruit pulps and popular flavor compounds, and production of commonly consumed tailor-made goat milk-based products have potential to overcome this limitation. In particular, certain probiotic bacteria release volatile compounds as a result of their metabolism, which are known to play a major role in the aroma profile and sensory aspects of the final products.

Is the caudal auricular axial pattern flap robust? A multi-centre cohort study of 16 dogs and 12 cats (2005 to 2016).

OBJECTIVE: To determine the frequency and type of healing complications arising after the use of the caudal auricular axial pattern flap to close defects on the head in dogs and cats. MATERIAL AND METHODS: Multi-centre retrospective cohort study. Centres were recruited by the Association for Veterinary Soft Tissue Surgery Research Cooperative. Medical records of 11 centres were reviewed, and data from all dogs and cats treated with a caudal auricular axial pattern flap were retrieved. The following data were recorded: signalment, reason for reconstruction, flap dimensions, anatomic landmarks used, histological diagnosis, flap healing and whether revision surgery was required. RESULTS: Twenty-eight cases were included: 16 dogs and 12 cats. Flap length: width ratio was approximately 3:1 and flap length extended to the scapular spine in most cases. Optimal wound healing occurred in five of 16 (31%) dogs and six of 12 (50%) cats. Wound dehiscence without flap necrosis occurred in one of 16 (6%) dogs and one of 12 (8%) cats. Wound dehiscence with flap necrosis occurred in 10 of 16 (63%) dogs and five of 12 (42%) cats. Revision surgery was performed in eight of 16 (50%) dogs and three of 12 (25%) cats. CLINICAL SIGNIFICANCE: The caudal auricular axial pattern flap can provide full thickness skin coverage for large defects on the head in dogs and cats. Partial flap necrosis is a common complication, and revision surgery may be required in order to achieve final wound closure.

Risk of exposure to air pollution among British children with and without intellectual disabilities.

BACKGROUND: Exposure to outdoor air pollution is a well-established risk factor for a range of adverse health conditions. No previous study has quantified the extent to which children with intellectual disability (ID) may be exposed to outdoor air pollution. METHODS: Secondary analysis of data extracted from the UK's Millennium Cohort Study, a nationally representative sample of over 18 000 UK children born 2000-2002. RESULTS: Averaging across ages, children with IDs were 33% more likely to live in areas with high levels of diesel particulate matter, 30% more likely to live in areas with high levels of nitrogen dioxide, 30% more likely to live in areas with high levels of carbon monoxide and 17% more likely to live in areas with high levels of sulphur dioxide. CONCLUSIONS: Levels of exposure to outdoor air pollution among children with ID are significantly higher than those of families of children without ID. Exposure to outdoor air pollution may be one of the pathways that contributes to the health inequities experienced by people with IDs.

Outcome and prognostic factors in medically treated canine prostatic carcinomas: A multi-institutional study.

Literature describing medical treatment of canine prostatic carcinoma (PC) is sparse. The aims of this study were to assess outcomes, including time to progression (TTP) and median survival time (MST), of canine PC treated with non-steroidal anti-inflammatory drugs (NSAIDs) and/or chemotherapy, and to identify prognostic factors. Records from 8 institutions were searched for dogs with cytologically or histologically confirmed PC without bladder involvement: 67 dogs were included. Presenting signs were urinary (25), gastrointestinal ([GI], 11) and systemic (3); 16 dogs had GI and urinary signs, 7 dogs had systemic signs with concurrent GI or urinary signs and in 5 dogs the tumour was an incidental finding. Out of 27 dogs, 9 (33%) had positive urine culture. Metastases were identified in 26 dogs to lymph nodes (19), lungs (10), bone (2) and liver (1). Treatment included NSAIDs and chemotherapy (32), NSAIDs alone (31) and chemotherapy alone (4). The overall MST was 82 days (range 9-752) and median TTP was 63 days (range 9-752). Dogs receiving NSAIDs combined with chemotherapy experienced a significantly longer MST (106 vs 51 days; P = .035) and TTP (76 vs 44 days; P = .02) compared to dogs receiving NSAIDs alone. Intact dogs and those with metastatic disease had significantly shorter MST (31 vs 90 days, P = .018 and 49 vs 109 days, P = .037, respectively); intact dogs also had significantly shorter TTP (25 vs 63 days, P = .0003). This study suggests that a combination of NSAIDs and chemotherapy may improve outcomes in canine PC. Metastatic disease and being entire negatively influenced prognosis.

Monopole production via photon fusion and Drell-Yan processes: MadGraph implementation and perturbativity via velocity-dependent coupling and magnetic moment as novel features.

In this work we consider point-like monopole production via photon-fusion and Drell-Yan processes in the framework of an effective U(1) gauge field theory obtained from conventional models describing the interaction of spin  magnetically-charged fields with ordinary photons, upon electric-magnetic dualisation. We present arguments based on such dualities which support the conjecture of an effective monopole-velocity-dependent magnetic charge. For the cases of spin- and spin-1 monopoles, we also include a magnetic-moment term κ , which is treated as a new phenomenological parameter and, together with the velocity-dependent coupling, allows for a perturbative treatment of the cross-section calculation. We discuss unitarity issues within these effective field theories, in particular we point out that in the spin-1 monopole case only the value κ = 1 may restore unitarity. However from an effective-field-theory point of view, this lack of unitarity should not be viewed as an impediment for the phenomenological studies and experimental searches of generic spin-1 monopoles, given that the potential appearance of new degrees of freedom in the ultraviolet completion of such models might restore it. The second part of the paper deals with an appropriate implementation of photon-fusion and Drell-Yan processes based on the above theoretical scenarios into MadGraph UFO models, aimed to serve as a useful tool in interpretations of monopole searches at colliders such as LHC, especially for photon fusion, given that it has not been considered by experimental collaborations so far. Moreover, the experimental implications of such perturbatively reliable monopole searches have been laid out.

Temozolomide alone or in combination with doxorubicin as a rescue agent in 37 cases of canine multicentric lymphoma.

Temozolomide (TMZ) is an alkylating agent previously used in conjunction with doxorubicin (DOX) to treat dogs with relapsed lymphoma. However, there are very limited data for this drug when used as single agent. The aim of this retrospective study was to evaluate the efficacy and toxicity of TMZ in dogs with relapsed multicentric lymphoma that failed multi-agent chemotherapy protocols, and compare the outcome to a group of dogs receiving the same drug in combination with DOX. Twenty-six patients were included in the TMZ group and 11 in the TMZ/DOX group. Responses were evaluated via retrospective review of the medical records. The overall median survival time (MST) for both groups was 40 days (range 1-527 days). For the TMZ group, median time to progression (TTP) was 15 days (range 1-202 days) and MST 40 days (range 1-527 days), with an overall response rate (ORR) of 32% and 46% recorded toxicities. For the TMZ/DOX group, median TTP was 19 days (range 2-87 days) and MST 24 days (range 3-91 days), with an ORR of 60% and 63% recorded toxicities. However, a proportion of haematological toxicoses may have gone undetected due to the absence of associated clinical signs. The difference in MST and TTP between the 2 groups was not statistically significant. Similarly, no negative prognostic factors were identified. Although responses were generally short lived, this study suggests that TMZ may achieve similar efficacy to TMZ/DOX whilst being associated with a lower frequency of recorded toxicities.

Vancomycin-intermediate Staphylococcus aureus isolates are attenuated for virulence when compared with susceptible progenitors.

OBJECTIVES: Vancomycin-intermediate Staphylococcus aureus (VISA) is associated with genetic changes that may also impact upon pathogenicity. In the current study, we compared the virulence of clinical VISA strains with their isogenic vancomycin-susceptible progenitors (VSSA). METHODS: Production of the critical virulence protein, α toxin, was assessed using Western blot analysis and was correlated to agr activity using a bioluminescent agr-reporter. Cytotoxicity and intracellular persistence were compared ex vivo for VSSA and VISA within non-professional phagocytes (NPP). Virulence and host immune responses were further explored in vivo using a murine model of bacteraemia. RESULTS: VISA isolates produced up to 20-fold less α toxin compared with VSSA, and this was corroborated by either loss of agr activity due to agr mutation, or altered agr activity in the absence of mutation. VISA were less cytotoxic towards NPP and were associated with enhanced intracellular persistence, suggesting that NPP may act as a reservoir for VISA. Infection with VSSA strains produced higher mortality in a murine bacteraemia model (≥90% 7-day mortality) compared with infection with VISA isolates (20% to 50%, p <0.001). Mice infected with VISA produced a dampened immune response (4.6-fold reduction in interleukin-6, p <0.001) and persistent organ bacterial growth was observed for VISA strains out to 7 days. CONCLUSIONS: These findings highlight the remarkable adaptability of S. aureus, whereby, in addition to having reduced antibiotic susceptibility, VISA alter the expression of pathogenic factors to circumvent the host immune response to favour persistent infection over acute virulence.

Search for Magnetic Monopoles with the MoEDAL Forward Trapping Detector in 13 TeV Proton-Proton Collisions at the LHC.

MoEDAL is designed to identify new physics in the form of long-lived highly ionizing particles produced in high-energy LHC collisions. Its arrays of plastic nuclear-track detectors and aluminium trapping volumes provide two independent passive detection techniques. We present here the results of a first search for magnetic monopole production in 13 TeV proton-proton collisions using the trapping technique, extending a previous publication with 8 TeV data during LHC Run 1. A total of 222 kg of MoEDAL trapping detector samples was exposed in the forward region and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges exceeding half the Dirac charge are excluded in all samples and limits are placed for the first time on the production of magnetic monopoles in 13 TeV pp collisions. The search probes mass ranges previously inaccessible to collider experiments for up to five times the Dirac charge.