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Background: Parents and carers supporting a family member presenting with behaviors of concern experience heightened stress. The Low Arousal Approach is a crisis management strategy which recognizes that stress, or physiological arousal, can be expressed through behaviors of concern. This approach aims to equip parents and carers to manage behaviors in a person-centered and non-confrontational way. There is a paucity of published research exploring the experiences of families applying this approach., Methods: Seventeen parents who had received training in the Low Arousal Approach were interviewed to gain their perspectives on supporting their family members using this approach., Results: Thematic analysis revealed themes relating to parental stress, which was related to external pressures, isolation, family stress, and challenges in their caring role. They described encountering negative narratives relating to self-criticism and negative judgments from others. Training in the Low Arousal Approach was related to being empowered through access to evidence, increased confidence, and increased ability to advocate for their family member's needs. Low Arousal was described as a "lifestyle" that enabled increased coping for the family unit as a whole., Discussion/conclusion: Findings indicate that it is vitally important to recognize the views of parents and carers, and these are equally as important as the views of professionals. We must understand parents' and carers' needs in order to provide adequate support., Competing Interests: SB-P, KM, TK-J, and MM were employed by Studio 3 Clinical Services Limited. AM is a director of Studio 3 Training Systems Ltd. and a Visiting Professor of Autism Studies at Birmingham City University. Funding was received from Studio 3 Training Systems Ltd. The funder was involved in the study design, analysis, interpretation of data, writing, and the decision to submit the study for publication. The remaining author declares that the research was conducted without any commercial or financial relationships that could potentially create a conflict of interest., (Copyright © 2024 McDonnell, Page, Bews-Pugh, Morgalla, Kaur-Johal and Maher.)

Background: Internal Medicine (IM) residents are required to perform bedside procedures for diagnostic and therapeutic purposes. Residents' experiences with procedures vary widely, for unclear reasons., Objective: To explore IM residents' experiences with performing bedside procedures and to identify barriers and facilitators to obtaining sufficient experience., Methods: Using an inductive, thematic approach, we conducted five individual semi-structured interviews and one focus group with seven IM residents (12 residents in total) during the 2017-2018 academic year at a Canadian tertiary care centre. We used iterative, open-ended questions to elicit residents' experiences, and barriers and facilitators, to performing bedside procedures. Transcripts were analyzed for themes using Braun and Clarke's method., Results: We identified four themes 1) Patient-specific factors such as body habitus and procedure urgency; 2) Systems factors such as time constraints and accessibility of materials; 3) Faculty factors including availability to supervise, comfort level, and referral preferences, and 4) Resident-specific factors including preparation, prior experiences, and confidence. Some residents expressed procedure-related anxiety and avoidance., Conclusion: Educational interventions aimed to improve procedural efficiency and ensure availability of supervisors may help facilitate residents to perform procedures, yet may not address procedure-related anxiety. Further study is required to understand better how procedure-averse residents can gain confidence to seek out procedures., Competing Interests: No conflicts of interest or funding, (© 2023 Louis, Lee, Page, Ginsburg; licensee Synergies Partners.)

Objective: Create a process map for emergency department (ED) presentations of surgical ectopic pregnancy, and identify areas of management amenable to quality improvement., Methods: A retrospective chart review of all patients undergoing surgical management of ectopic pregnancy at a large, urban, academic tertiary care centre from 2015 to 2017 was performed., Results: Seventy-three patients were included. There were 6 (8.2%) unstable A cases (recommended time to operating room [OR] 0-2 hours), 23 (31.5%) stable A cases, and 44 (60%) B cases (recommended time to OR 2-8 hours). The percent of patients who were in the OR within the recommended time window were 6 (100%) for unstable A cases, 13 (56%) stable A cases, and 29 (65.9%) stable B cases, respectively (P = 0.139). Notable time delays include the time from gynaecology referral to the time seen by gynaecology (29.7% of total wait time for stable A cases from ED to OR) and the time the OR was booked to the time the patient was brought to the OR (53.2% of total wait time for stable B cases). Of the patients seen by physician at the emergency department first, the time from triage to the OR was significantly shorter for patients that received bedside ultrasound only (0.67 ± 0.5 hours vs. 2.1 ± 1.8 hours [P = 0.007])., Conclusion: This is the first study to map the ED presentation of surgical ectopic pregnancy. The management of ectopic pregnancy would benefit from the development of surgical triage decision aids, a surgical care pathway, and increased use of screening bedside ultrasound., (Copyright © 2022 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objectif: Fournir un algorithme fondé sur des données probantes pour orienter le diagnostic et la prise en charge de la grossesse de localisation indéterminée et de la grossesse ectopique tubaire ou non tubaire., Population Cible: Toutes les patientes en âge de procréer. BéNéFICES, RISQUES ET COûTS: La mise en œuvre de la présente directive a pour objectif de bénéficier aux patientes ayant obtenu un résultat positif pour la sous-unité bêta de la gonadotrophine chorionique et de fournir aux médecins un algorithme normalisé pour l'expectative et le traitement pharmacologique ou chirurgical en cas de grossesse de localisation indéterminée et de grossesse ectopique tubaire ou non tubaire. DONNéES PROBANTES: Les termes de recherche suivants ont été entrés dans les bases de données PubMed-Medline et Cochrane en 2018 : cesarean section, chorionic gonadotropin, beta subunit, human/blood, fallopian tubes/surgery, female, fertility, humans, infertility, laparoscopy, methotrexate, methotrexate/administration & dosage, methotrexate/therapeutic use, pregnancy (abdominal, angular, cervix, cornual, ectopic, ectopic/diagnosis, ectopic/diagnostic imaging, ectopic/drug therapy, ectopic/epidemiology, ectopic/mortality, ectopic/surgery, heterotopic, interstitial, isthmo-cervical, ovarian, tubal, unknown location), recurrence, risk factors, salpingectomy, salpingostomy, tubal pregnancy, ultrasonography, doppler ultrasonography et prenatal. Les articles retenus sont des essais cliniques randomisés, des méta-analyses, des revues systématiques, des études observationnelles et des études de cas. Des publications supplémentaires ont été sélectionnées à partir des notices bibliographiques de ces articles. Seuls les articles en anglais ont été examinés. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la solidité des recommandations en utilisant la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et faibles). PUBLIC VISé: Obstétriciens-gynécologues, médecins de famille, urgentologues, sages-femmes, infirmières autorisées, infirmières praticiennes, étudiants en médecine, résidents et moniteurs cliniques. DÉCLARATIONS SOMMAIRES (CLASSEMENT GRADE ENTRE PARENTHèSES): RECOMMANDATIONS (CLASSEMENT GRADE ENTRE PARENTHèSES)., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To provide an evidence-based algorithm to guide the diagnosis and management of pregnancy of unknown location and tubal and nontubal ectopic pregnancy., Target Population: All patients of reproductive age., Benefits, Harms, and Costs: The implementation of this guideline aims to benefit patients with positive β-human chorionic gonadotropin results and provide physicians with a standard algorithm for expectant, medical, and surgical treatment of pregnancy of unknown location and tubal pregnancy and nontubal ectopic pregnancies., Evidence: The following search terms were entered into PubMed/Medline and Cochrane in 2018: cesarean section, chorionic gonadotropin, beta subunit, human/blood, fallopian tubes/surgery, female, fertility, humans, infertility, laparoscopy, methotrexate, methotrexate/administration & dosage, methotrexate/therapeutic use, pregnancy (abdominal, angular, cervix, cornual, ectopic, ectopic/diagnosis, ectopic/diagnostic imaging, ectopic/drug therapy, ectopic/epidemiology, ectopic/mortality, ectopic/surgery, heterotopic, interstitial, isthmo-cervical, ovarian, tubal, unknown location), recurrence, risk factors, salpingectomy, salpingostomy, tubal pregnancy, ultrasonography, doppler ultrasonography, and prenatal. Articles included were randomized controlled trials, meta-analyses, systematic reviews, observational studies, and case reports. Additional publications were identified from the bibliographies of these articles. Only English-language articles were reviewed., Validation Methods: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations)., Intended Audience: Obstetrician-gynaecologists, family physicians, emergency physicians, midwives, registered nurses, nurse practitioners, medical students, and residents and fellows., Summary Statements (grade Ratings in Parentheses): RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES)., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Models of daytime and nighttime on-call responsibilities for residents vary across internal medicine training programs, but there are few data regarding residents' perceptions of their on-call experiences. The authors sought to understand what residents perceive as the benefits and detriments of 24-hour, in-house call, a perspective instrumental to informing change., Method: The authors conducted in-depth individual interviews and focus groups between December 2018 and March 2019 with 17 internal medicine residents from postgraduate years 1, 2, and 3 at the University of Toronto about their on-call experiences. Using constructivist grounded theory, the authors developed a framework to understand the residents' perceived benefits and drawbacks of 24-hour in-house call., Results: Residents' experiences on call were grouped into 7 themes regarding negative and positive aspects of call. Participants reported multidimensional fatigue related to call, including decision fatigue, emotional fragility and lability, and loss of empathy, and also reported that call adversely affected their personal lives. Residents expressed conflicting opinions as to whether prolonged duty hours affected patient outcomes. In contrast, residents also expressed benefits to call, including that overnight call led to increased autonomy and decision-making skills and provided preparation for future careers as independent internists. They described developing camaraderie and a sense of belonging to a team with coresidents overnight. Lastly, residents described occupying different roles during regular duty hours and while on call-daytime roles revolved around follow-up of previously admitted patients and administrative tasks, while overnight duties centered on initial workup and medical stabilization of referred patients., Conclusions: Understanding the nuanced phenomenon of being on call from the perspective of those who live through it is a critical step in creating evidence-based educational policies. New call models should emphasize resident autonomy and decision making and should include a consideration of residents' perceived differences between daytime and on-call roles., (Copyright © 2020 by the Association of American Medical Colleges.)

This investigation surveyed the gynaecologic services and management available to women experiencing early pregnancy complications in the province of Ontario, Canada. The Chiefs of Gynaecology/Obstetrics of 61 Ontario hospitals were invited to complete a 55-item, online questionnaire using modified Dillman methodology. Forty-three hospital site respondents completed the survey (a response rate of 70.5%). It was reported that 18 (41.9%) hospitals had access to an early pregnancy assessment unit (EPAU), and 12 (66.7%) EPAUs had ≤2 days between the referral and the first appointment. Of the 25 (58.1%) hospital respondents without an EPAU, 14 (56.0%) reported previous consideration of creating an EPAU. At these hospitals, patients with early pregnancy complications have access to care through the ED ( n  = 22, 88.0%), obstetricians/gynaecologists ( n  = 22, 88.0%), person on-call ( n  = 16, 64.0%), family physicians ( n  = 11, 44.0%) or midwives ( n  = 9, 36.0%). This investigation found great heterogeneity in the care accessible to women experiencing early pregnancy complications in hospitals in Ontario, Canada.Impact statement What is already known on this subject? Early pregnancy assessment units (EPAUs) are the standard for evaluating and caring for complications of early pregnancy. It has been well documented that EPAUs result in positive health service outcomes such as more cost-effective care, more timely management, and improved quality of care and patient satisfaction. What do the results of this study add? This investigation found that the province of Ontario, Canada has begun to adopt the EPAU model; however, a great heterogeneity exists in the care accessible to women experiencing early pregnancy complications throughout the province. Nonetheless, where EPAUs are available, they provide a structured referral system for women experiencing complications of early pregnancy that require gynaecologic assessment, such as ectopic pregnancy, providing close follow-up and predictable pathways of care for this patient population. What are the implications of these findings for clinical practice and/or further research? This study highlights the need for hospitals in the province of Ontario to improve their current service delivery models for women experiencing early pregnancy complications. Further research should be undertaken to determine whether the positive health service outcomes of EPAUs are also relevant in the Canadian healthcare system.

Purpose: Oxytocin is a commonly used drug in the labor and delivery unit. There are wide variations in oxytocin use between countries and medical centers, which may reflect the lack of structured guidelines. The aim of our study was to evaluate the need of oxytocin checklist in labor and delivery unit, while assessing the management of oxytocin with and without such a checklist., Methods: This study was conducted in a single, university-affiliated medical center in two phases: before and after the implementation of an oxytocin checklist in the labor and delivery unit (2016-2017). Six experts reviewed cardiotocographs of deliveries performed in an urgent Cesarean delivery due to non-reassuring fetal heart rate, after completing at least 4 h of oxytocin infusion for induction or augmentation of labor. The experts included three obstetricians, a midwife, and two obstetrical expert nurses, who were tasked to conclude whether oxytocin was managed properly or not. Each case was reviewed by two reviewers separately. A total of 100 cases were reviewed; 50 before the oxytocin checklist implementation, and 50 after that implementation., Results: We did not find a difference in the reviewers' assessment of oxytocin management before and after the institutional implementation of the checklist. Additionally, there were significant inconsistencies and inter-observer variations in their assessment before and after the checklist implementation., Conclusion: The implementation of an institutional oxytocin checklist did not affect expert assessment of the use of oxytocin in labor.

This article explores ethical decision-making surrounding clinical holding of children and young people in healthcare environments with the aim of enhancing autonomy and engagement on their behalf. A considerable body of evidence, published over the last 20 years, suggests that this complex and challenging area of practice is not always well managed, with mixed messages about the nature of consent, choice and negotiated practice countered by best interests decisions taking precedence ahead of the child's wishes. An ethical framework is proposed comprising four levels of value-based interventions and how they may be applied in clinical practice, allowing for increased engagement, empowerment and support on behalf of children and young people in relation to clinical holding decisions., Competing Interests: None declared, (©2019 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Healthcare staff routinely use clinical holding to help infants, children or young people stay still when treatment is being administered, to prevent children or young people from interfering with the treatment, or when invasive examinations are being carried out. However, healthcare staff rarely have any formal discussion with children and young people, or their parents, on the techniques used for clinical holding. Visual tools are important when talking to children or young people about their healthcare, and a website with images of clinical holds would allow staff to discuss relevant holds with their patients. In this article, we describe a collaboration between Birmingham City University and Birmingham Children's Hospital to develop a website that presents 3D images of clinical holds, outlining how we introduced it to staff in the clinical areas that would benefit from it and how we have been evaluating its effectiveness. We hope this website will formalise the professional discussion of clinical hold techniques. This will allow information on the appropriate holds for different situations to be documented, which will enhance best practice. In addition, the website should provide information needed to allow children, young people and their parents to give true, informed consent for any procedures they need.

The canal of Nuck is a remnant of a peritoneal evagination associated with the round ligament in women. Rarely, the canal of Nuck can remain patent allowing for development of cysts. These cysts are difficult to diagnose due to their rare incidence and because they are often mistaken for other causes of inguinal pain in women. This case series of three women presenting with groin or labial masses highlights the role of sonography as the primary imaging modality in the diagnosis of canal of Nuck cysts. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:175-178, 2017., (© 2016 Wiley Periodicals, Inc.)

Nurses hold children to administer treatment, prevent treatment interference and undertake clinical assessments, which can sometimes be invasive, as part of their regular duties. Clinical holding ensures this treatment or assessment is carried out safely, however, it has been reported that there is little training available in this area. This article explores the prevalent clinical holding techniques used by nursing staff when caring for children with behaviours that challenge. As an initial insight into what the researchers hope will become a more in-depth 2-year study, this investigation looks to explore current practice when holding children and the factors influencing this. It is hoped that this will inform the development of a training package offered to nurses when caring for these children. Thirteen semi-structured interviews took place with a small group of nurses, which were given thematic analysis. The overarching themes influencing holding practice were the nursing role itself along with intrinsic and external factors.

Background: Post-infectious irritable bowel syndrome (PI-IBS) due to traveler's diarrhea is the second most common illness seen in post-travel clinics, yet its optimal management remains unknown. We performed a systematic review to evaluate treatment efficacy in PI-IBS., Methods: We searched Medline, EMBASE, LILACS, CINAHL, CAB abstracts, and the Cochrane Library to February 3, 2014 for intervention studies of the pharmacologic and non-pharmacologic management of PI-IBS and examined the evidence according to a modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scale., Results: Of 336 records, 9 studies were included. Eight studies of pharmacologic interventions examined 5 agents (mesalazine or mesalamine, ondansetron, prednisolone, cholestyramine, and metronidazole). One study examined the non-pharmacologic intervention of different infant nutritional formulas following acute gastroenteritis. The quality of the evidence to date was low, with small sample size (fewer than 50 participants) and short duration of follow-up. Overall, the efficacy of pharmacological treatment ranged from no benefit (ondansetron and prednisolone) to moderately beneficial (cholestyramine and metronidazole). The evidence for mesalazine was equivocal: one study showed benefit, two others showed none., Conclusions: Heterogeneity in outcome measures and low strength of evidence preclude recommendations on the optimal management of PI-IBS by a specific agent. More comparative intervention research into PI-IBS treatment is needed for consistent best practice in PI-IBS management. Clinicians may elect to pursue therapeutic trials of mesalazine, cholestyramine, or metronidazole in individual patients, but should be aware that data supporting the efficacy of these agents is limited.

Prosthetic joint infections (PJIs) are commonly caused by pathogens such as Staphylococcus aureus and coagulase-negative staphylococci; however, other microbial etiologies and specific risk factors are increasingly recognized. Pasteurella multocida is a Gram-negative coccobacillus that is part of the normal oral flora in many animals, and is particularly common in dogs and cats. PJIs caused by P multocida have been reported only rarely in the literature and typically occur in the context of an animal bite or scratch. The present article describes a P multocida joint infection that occurred after a dog lick and complicated a two-stage revision arthroplasty. A comprehensive review of the literature regarding P multocida PJIs follows.

Holding practices are employed to help a child or young person stay still during the administration of treatments, prevent treatment interference or to undertake an examination, which can sometimes be invasive. The aim of this study was to explore assumptions and practices of holding to develop theories about teaching practices following Grounded Theory methodology for undergraduate nursing students, university lecturers and clinical mentors. The practice of therapeutic holding is often covert and not considered to be part of the treatment per se, which has led to concealment and a reticence to discuss practices openly. This study identified that there is variance in the experiences and practices. Prominent themes that emerged were a lack of clarity and lack of training. It appears that therapeutic holding practices have moved from being viewed as 'uncontested' (practice is not disputed) to 'indifferent' (where there is denial about this practice). These findings have serious implications for current practice and future training.

Physical holds are used to help children and young people receive clinical care in situations where their behaviour may limit the ability of nurses and allied professionals to deliver treatment effectively. This article provides an overview of a qualitative study of 11 nurses and allied professionals who were interviewed with semi-structured questions. The major findings suggest there is a lack of clear and agreed terminology and nurses and allied professionals are guessing at how to describe the practice. As a result, there was no discussion or documentation of the practices of holding (whether successful or unsuccessful) within the clinical area. For the last decade, professional opinion was that this is an 'uncontested practice'. It can therefore be questioned whether this practice has moved from being 'uncontested' to 'indifferent'. Nurses and allied professionals need to revive a common definition of 'good' around the actions of holding, which can hopefully lead to holding skills being more clearly defined and evidence-based.

Escherichia coli O157:H7-associated hemolytic-uremic syndrome (HUS) is characterized by profound prothrombotic abnormalities. Endothelial dysfunction, manifested as dysregulation of angiopoietins 1 and 2 (Ang-1/2), could underlie HUS pathophysiology. We measured Ang-1/2 in 77 children with E. coli O157:H7 infection. Ang-1, Ang-2, and the Ang-2/Ang-1 ratio were significantly different in HUS vs the pre-HUS phase of illness or uncomplicated infection. Angiopoietin dysregulation preceded HUS and worsened as HUS developed. In vitro exposure of human microvascular endothelial cells to Shiga toxin recapitulated the in vivo observations. Angiopoietin regulation is profoundly affected before and during HUS, reflecting that subclinical endothelial dysfunction precedes overt microangiopathy.

Endothelial dysfunction contributes to the pathogenesis of a variety of potentially serious infectious diseases and syndromes, including sepsis and septic shock, hemolytic-uremic syndrome, severe malaria, and dengue hemorrhagic fever. Because endothelial activation often precedes overt endothelial dysfunction, biomarkers of the activated endothelium in serum and/or plasma may be detectable before classically recognized markers of disease, and therefore, may be clinically useful as biomarkers of disease severity or prognosis in systemic infectious diseases. In this review, the current status of mediators of endothelial cell function (angiopoietins-1 and -2), components of the coagulation pathway (von Willebrand Factor, ADAMTS13, and thrombomodulin), soluble cell-surface adhesion molecules (soluble E-selectin, sICAM-1, and sVCAM-1), and regulators of vascular tone and permeability (VEGF and sFlt-1) as biomarkers in severe infectious diseases is discussed in the context of sepsis, E. coli O157:H7 infection, malaria, and dengue virus infection.

Enterohemorrhagic Escherichia coli (EHEC; Shiga toxin/verotoxin-producing E. coli) can cause bloody diarrhea and the hemolytic-uremic syndrome (HUS), typically following consumption of contaminated food (including ground beef, leafy greens, and sprouts) and water. Often associated with foodborne outbreaks, EHEC possess unique virulence factors that facilitate effective colonization of the human gastrointestinal tract and subsequent release of Shiga toxin. This article reviews the epidemiology, pathogenesis, clinical presentation, treatment, and prevention of EHEC infections, focusing on E. coli O157:H7, the serotype most common in North America, and E. coli O104:H4, the serotype responsible for the EHEC outbreak in Germany in 2011., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The benefits of breast milk to the newborn infant are well established. The Canadian Paediatric Society recommends exclusive breastfeeding for the first 6 months of life for healthy, term infants. Mothers of premature newborns, however, may have difficulty providing an adequate supply of breast milk. Domperidone is officially used as a prokinetic agent. However, it is used widely around the world as a galactogogue. Despite its widespread use as a galactogogue, only a small number of investigators have studied domperidone for this indication., Aims: The purpose of this study was to determine an optimal dosage of domperidone as a galactogogue., Methods: Eligible subjects were randomized to receive domperidone 10 mg 3 times daily or domperidone 20 mg 3 times daily for 4 weeks. At week 5, the frequency was decreased to twice daily in both groups, and finally once daily for week 6., Results: Over the entire first 4-week period, there was a significant increase in daily milk volumes within each group (P < .01). The between-group difference over this period, although not statistically significant, was clinically significant. Additionally, there was no significant within- or between-group difference during weeks 5 and 6., Conclusion: A dose of domperidone of 20 mg, 3 times daily instead of 10 mg, 3 times daily was associated with a clinical, but not statistically significant, increase in milk production.

Hemolytic uremic syndrome (HUS) is a potentially life-threatening condition. It often occurs after gastrointestinal infection with E. coli O157:H7, which produces Shiga toxins (Stx) that cause hemolytic anemia, thrombocytopenia, and renal injury. Stx-mediated changes in endothelial phenotype have been linked to the pathogenesis of HUS. Here we report our studies investigating Stx-induced changes in gene expression and their contribution to the pathogenesis of HUS. Stx function by inactivating host ribosomes but can also alter gene expression at concentrations that minimally affect global protein synthesis. Gene expression profiling of human microvascular endothelium treated with Stx implicated a role for activation of CXCR4 and CXCR7 by their shared cognate chemokine ligand (stromal cell-derived factor-1 [SDF-1]) in Stx-mediated pathophysiology. The changes in gene expression required a catalytically active Stx A subunit and were mediated by enhanced transcription and mRNA stability. Stx also enhanced the association of CXCR4, CXCR7, and SDF1 mRNAs with ribosomes. In a mouse model of Stx-mediated pathology, we noted changes in plasma and tissue content of CXCR4, CXCR7, and SDF-1 after Stx exposure. Furthermore, inhibition of the CXCR4/SDF-1 interaction decreased endothelial activation and organ injury and improved animal survival. Finally, in children infected with E. coli O157:H7, plasma SDF-1 levels were elevated in individuals who progressed to HUS. Collectively, these data implicate the CXCR4/CXCR7/SDF-1 pathway in Stx-mediated pathogenesis and suggest novel therapeutic strategies for prevention and/or treatment of complications associated with E. coli O157:H7 infection.

Colony-stimulating factors (CSFs) are attractive adjunctive anti-infective therapies. Used to enhance innate host defenses against microbial pathogens, the myeloid CSFs increase absolute numbers of circulating innate immune effector cells by accelerating bone marrow production and maturation, or augment the function of those cells through diverse effects on chemotaxis, phagocytosis, and microbicidal functions. This article summarizes the evidence supporting the accepted clinical uses of the myeloid CSFs in patients with congenital or chemotherapy-induced neutropenia, and presents an overview of proposed and emerging uses of the CSFs for the prevention and treatment of infectious diseases in other immunosuppressed and immunocompetent patient populations., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Streptococcal toxic shock syndrome (STSS) is characterized by diffuse vascular leak resulting from widespread endothelial activation. Angiopoietin-1 and -2 (Ang-1 and Ang-2), which are important regulators of endothelial quiescence and activation, respectively, are dysregulated in certain diseases that are associated with endothelial dysfunction, but they have not been previously investigated in STSS. Plasma Ang-1 and Ang-2 concentrations were measured in 37 patients with invasive streptococcal infection with and without concurrent STSS. Greater angiopoietin dysregulation (decreased Ang-1 and increased Ang-2) occurred in STSS than in invasive infection without shock; dysregulation decreased with convalescence. These results suggest that systemic Ang-1 and Ang-2 dysregulation is associated with disease severity in invasive streptococcal infection and that plasma levels of Ang-1 and Ang-2 may serve as clinically informative biomarkers in STSS.

Lyme neuroborreliosis is a tick-borne illness with central and peripheral nervous system manifestations. Clinical features and methods for accurate diagnosis differ across world regions owing to different causative Borrelia species. The importance of these distinctions is highlighted by a 12-year-old Canadian girl who acquired Lyme neuroborreliosis in Europe.

Efforts to reduce injuries associated with patient handling are often based on tradition and personal experience rather than sound educational theory. The purpose of this article is to summarize current evidence for educational interventions designed to reduce primary care staff injuries: a significant problem for decades. Evidence suggests that the current 'classroom' teaching of moving and handling is ineffective. There is a growing body of evidence to support newer interventions that are effective or show promise in reducing musculoskeletal injuries in health professionals (Freitag et al, 2007). The authors discuss potential solutions through moving and handling-related motion capture simulation and the use of e-learning to promote an understanding of the principles associated with patient handling tasks.

Unlabelled: Insulin is neuroprotective following transient global brain ischemia; however, the mechanisms by which insulin exerts its salutary effects remain unclear., Objective: We assessed insulin's effect on the PI3K-Akt survival system and consequent modulation of the pro-apoptotic proteins Bim, Bad and FoxO3a., Methods: We utilized rats subjected to 10 minutes of global brain ischemia, with or without insulin administered at the onset of reperfusion., Results: In sham-operated animals, minimal pAkt immunofluorescence was detected in the CA1. Moreover, at 30 minute reperfusion, there was no change in pAkt in CA1 neurons. Single bolus high-dose insulin treatment resulted in an early increase in pAkt after 30 minutes, preservation of CA1 neurons to 14 days of reperfusion and preservation of spatial learning ability. Insulin treatment increased cytoplasmic and nuclear staining for pAkt in both CA1 and cortex. Insulin-induced Akt phosphorylation was suppressed by the PI3K inhibitor wortmannin. Neither reperfusion nor insulin induced any change in the phosphorylation or subcellular localization of FoxO3a, Bim or Bad. A single bolus of high-dose insulin reduced CA1 neuronal cell death and thus represents a potential therapeutic intervention for global brain ischemia., Discussion: These results reveal that proximal elements of a known cell-survival pathway are triggered by high-dose insulin during early reperfusion. Insulin induces robust PI3K-dependent phosphorylation of Akt by 30 minute reperfusion and results in improvement of hippocampal structure and function. However, the Akt substrates FoxO3a, Bim and Bad do not undergo corresponding changes in phosphorylation or subcellular localization in this model of global brain ischemia. The downstream components of insulin-induced Akt survival signaling after transient global brain ischemia remain to be identified.

Purpose of Review: Infections continue to cause significant morbidity and mortality in SOT recipients despite major advances in immunosuppressive and antimicrobial regimens. Immunomodulatory cytokines provide a potential means to augment the host immune response to infection. This review will focus on cytokine therapy for the prophylaxis and treatment of infections in solid organ transplant recipients, and will speculate on the potential for further advances in the field., Recent Findings: In kidney and liver transplant recipients, granulocyte colony-stimulating factor (G-CSF) has been used successfully to reverse ganciclovir-induced neutropenia or cytomegalovirus-induced neutropenia. Although G-CSF also reversed corticosteroid-induced suppression of the neutrophil respiratory burst in vitro, prophylactic G-CSF failed to reduce infections or mortality in nonneutropenic solid organ transplant recipients. Published clinical experience with granulocyte-macrophage colony-stimulating factor (GM-CSF) in this population has been limited to case reports and a small case series, whereas the use of macrophage colony-stimulating factor (M-CSF) or interferon-gamma (IFN-gamma) has not been systematically investigated in controlled clinical trials., Summary: Despite encouraging results in vitro and in preclinical models, immunomodulatory cytokines have not met expectations when administered to SOT recipients. Nonetheless, the principle of selective enhancement of innate immunity for the prevention and treatment of infections in this patient population has promise and warrants further study.

Nurses and other carers of people with learning disabilities must be able to manage choking events and perform basic life support effectively. UK guidelines for assessment of airway obstruction and for resuscitation do not take account of the specific needs of people with profound multiple learning disability. For example, they fail to account for inhibited gag and coughing reflexes, limited body movements or chest deformity. There are no national guidelines to assist in clinical decisions and training for nurses and carers. Basic life support training for students of learning disability nursing at Birmingham City University is supplemented to address these issues. The authors ask whether such training should be provided for all nurses including those caring for children and young people. They also invite comment and discussion on questions related to chest compression and training in basic life support for a person in a seated position.

Posaconazole is the newest antifungal agent to be approved for use in Canada. With excellent in vitro activity against a broad spectrum of yeasts and filamentous fungi, as well as having a well-tolerated oral formulation, posaconazole offers many potential advantages. Of particular interest are its seemingly lower potential for cross-resistance with other azoles and its activity (unique among oral antifungal agents) against the zygomycetes. As the incidence of both common and uncommon fungal infections increases commensurate with the growing population of immunocompromised individuals, posaconazole may ultimately become an important therapeutic option. The present article reviews the in vitro and in vivo data describing its activity, and focuses on both the proven and the potential clinical applications of this new triazole agent.

Objectives: Within the first few minutes of reperfusion after global brain ischemia, there is a severe depression of protein translation owing to phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF2). There is a 67 kDa peptide (p67) that, in its glycosylated form, binds to eIF2 and protects eIF2alpha from phosphorylation. Moreover, cells with high p67 content exhibit enhanced resistance to eIF2alpha phosphorylation. To examine the possibilities that deglycosylation of brain p67 occurs during ischemia and/or early reperfusion or that p67 deglycosylation may be more extensive in the vulnerable neurons, these experiments were undertaken to characterize the localization and activation state of p67 during early brain reperfusion, Methods: Western blots using antibodies that recognize total p67, glycosylated p67 and phosphorylated eIF2alpha were used to characterize total p67 and glycosylated p67 during reperfusion-induced phosphorylation of eIF2alpha. We also characterized the immunohistochemical distribution of glycosylated p67 before and after brain ischemia and reperfusion., Results: There was a large increase in phosphorylated eIF2alpha, but there was no decrease in the levels of total or glycosylated p67 from those observed in controls following 10 minutes complete brain ischemia and 10 or 60 minutes subsequent reperfusion. Furthermore, there was no reduction in localized immunostaining for glycosylated p67 in vulnerable neurons during ischemia and reperfusion., Discussion: It does not appear that p67 plays a significant role in regulating the phosphorylation of eIF2alpha following transient brain ischemia.

Endothelial function is dependent on the generation of nitric oxide (NO) by the enzyme endothelial NO synthase (eNOS). One functional coding polymorphism of the eNOS gene (G894-->T) is associated with reduced enzyme activity, increased coronary heart disease, and the development of end-stage renal failure. Because gender and renin-angiotensin system activation also play key roles in the development of renal and cardiovascular disease and because NO plays a role in the response to angiotensin II (AngII), it was hypothesized that the eNOS gene G894-->T polymorphism would be a determinant of the systemic and renal vascular response to AngII. Fifty young, healthy, normotensive individuals who were on a controlled sodium and protein diet for 1 wk underwent assessment of BP and renal hemodynamic function at baseline and during AngII infusion (4 ng/kg per min for 45 min). Participants were genotyped for the eNOS gene G894-->T polymorphism and then segregated into groups on the basis of gender and genotype (GG versus GT/TT). Baseline values for renal blood flow, effective renal plasma flow, and GFR were lower in men with the T allele compared with men who were homozygous for the G allele (P = 0.03), but the polymorphism was not associated with renal hemodynamic function in women. The BP responses to AngII were similar in men and women regardless of genotype. Both multivariate linear regression and analysis of covariance (ANCOVA) revealed a relationship between gender and genotype. Men with the GT/TT genotype exhibited a significantly greater decrease in GFR (P = 0.04) in response to AngII than did those with the GG genotype. This association was not observed in women. The eNOS gene G894-->T polymorphism is a determinant of both baseline renal hemodynamic function and the hemodynamic response to AngII in men but not in women.

Upon brain reperfusion following ischemia, there is widespread inhibition of neuronal protein synthesis that is due to phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha), which persists in selectively vulnerable neurons (SVNs) destined to die. Other investigators have shown that expression of mutant eIF2alpha (S51D) mimicking phosphorylated eIF2alpha induces apoptosis, and expression of non-phosphorylatable eIF2alpha (S51A) blocks induction of apoptosis. An early event in initiating apoptosis is the release of cytochrome c from mitochondria, and cytochrome c release corresponds to the selective vulnerability of hippocampal CA1 neurons in rats after transient global cerebral ischemia. At present the signaling pathways leading to this are not well defined. We hypothesized that persistent eIF2alpha(P) reflects injury mechanisms that are causally upstream of release of cytochrome c and induction of apoptosis. At 4 h of reperfusion following 10-min cardiac arrest, vulnerable neurons in the striatum, hippocampal hilus and CA1 showed colocalized intense immunostaining for both persistent eIF2alpha(P) and cytoplasmic cytochrome c, while resistant neurons in the dentate gyrus and elsewhere did not immunostain for either. A lower intensity of persistent eIF2alpha(P) immunostaining was present in cortical layer V pyramidal neurons without cytoplasmic cytochrome c, possibly reflecting the lesser vulnerability of this area to ischemia. We did not observe cytoplasmic cytochrome c in any neurons that did not also display persistent eIF2alpha(P) immunostaining. Because phosphorylation of eIF2alpha during early brain reperfusion is carried out by PERK, these findings suggest that there is prolonged activation of the unfolded protein response in the reperfused brain.