Structural and functional studies on a mesophilic stationary phase survival protein (Sur E) from Salmonella typhimurium

SurE, the stationary-phase survival protein of Salmonella typhimurium, forms part of a stress survival operon regulated by the stationary-phase RNA polymerase alternative sigma factor. SurE is known to improve bacterial viability during stress conditions. It functions as a phosphatase specific to nucleoside monophosphates. In the present study we reported the X-ray crystal structure of SurE from Salmonella typhimurium. The protein crystallized in two forms: orthorhombic F222; and monoclinic C2. The two structures were determined to resolutions of 1.7 and 2.7Å, respectively. The protein exists as a domain-swapped dimer. The residue D230 is involved in several interactions that are probably crucial for domain swapping. A divalent metal ion is found at the active site of the enzyme, which is consistent with the divalent metal ion-dependent activity of the enzyme. Interactions of the conserved DD motif present at the N-terminus with the phosphate and the Mg2+ present in the active site suggest that these residues play an important role in enzyme activity. The divalent metal ion specificity and the kinetic constants of SurE were determined using the generic phosphatase substrate para-nitrophenyl phosphate. The enzyme was inactive in the absence of divalent cations and was most active in the presence of Mg2+. Thermal denaturation studies showed that S. typhimurium SurE is much less stable than its homologues and an attempt was made to understand the molecular basis of the lower thermal stability based on solvation free-energy. This is the first detailed crystal structure analysis of SurE from a mesophilic organism

Peri‐operative cardiac arrest in children as reported to the 7th National Audit Project of the Royal College of Anaesthetists

The 7th National Audit Project of the Royal College of Anaesthetists studied peri‐operative cardiac arrest. An activity survey estimated UK paediatric anaesthesia annual caseload as 390,000 cases, 14% of the UK total. Paediatric peri‐operative cardiac arrests accounted for 104 (12%) reports giving an incidence of 3 in 10,000 anaesthetics (95%CI 2.2–3.3 per 10,000). The incidence of peri‐operative cardiac arrest was highest in neonates (27, 26%), infants (36, 35%) and children with congenital heart disease (44, 42%) and most reports were from tertiary centres (88, 85%). Frequent precipitants of cardiac arrest in non‐cardiac surgery included: severe hypoxaemia (20, 22%); bradycardia (10, 11%); and major haemorrhage (9, 8%). Cardiac tamponade and isolated severe hypotension featured prominently as causes of cardiac arrest in children undergoing cardiac surgery or cardiological procedures. Themes identified at review included: inappropriate choices and doses of anaesthetic drugs for intravenous induction; bradycardias associated with high concentrations of volatile anaesthetic agent or airway manipulation; use of atropine in the place of adrenaline; and inadequate monitoring. Overall quality of care was judged by the panel to be good in 64 (62%) cases, which compares favourably with adults (371, 52%). The study provides insight into paediatric anaesthetic practice, complications and peri‐operative cardiac arrest

Survival at 10 years following lower extremity amputations in patients with diabetic foot disease

This is an accepted manuscript of an article published by Springer in Endocrine on 12/04/2020, available online: https://doi.org/10.1007/s12020-020-02292-7 The accepted version of the publication may differ from the final published version.© 2020, Springer Science+Business Media, LLC, part of Springer Nature. Background: Amputations are associated with markedly reduced long-term survival in patients with diabetic foot disease. However, there is paucity of long-term survival data in published literature. Methods: We searched the electronic case records and laboratory details of patients who underwent amputations between 1997 and 2006 to obtain at least 10 years of follow up data after the surgery to assess the survival rates and possible risk factors reducing survival in the year 2016. Amputation level below ankle was considered as minor and above ankle as major amputations. Results: Of the 233 cases (159 males; median age 68 years), 161 had major amputations. Of the 72 cases who had minor amputations initially, 63 needed a further amputation or contralateral amputation on follow up. One hundred seventy-seven patients (76%) were not alive after 10 years of follow up. The survival rates at 1, 3, 5, 7, and ≥10 years were 64%, 50%, 40%, 34%, and 24%, respectively. Maximum number of deaths occurred within 4 months of amputations. There was no difference between survival rates following major or minor amputations and among males or females. The only statistically significant parameter affecting lower survival rate was age ≥70 years, with each additional year of age increasing the hazard by a factor of 1.039 (95% CI: 1.024–1.054) or 3.9% (2.4–5.4%). Conclusions: Five-year and 10-year survival rates were 40% and 24%, respectively, following diabetic foot amputations. Higher age ≥70 years was associated with lower survival rate compared with younger age groups after lower extremity amputations.Published versio

Protocol for a Randomized Multiple Center Trial of Conservative Versus Liberal Oxygenation Targets in Critically Ill Children (Oxy-PICU): Oxygen in Paediatric Intensive Care

OBJECTIVES: Oxygen administration is a fundamental part of pediatric critical care, with supplemental oxygen offered to nearly every acutely unwell child. However, optimal targets for systemic oxygenation are unknown. Oxy-PICU aims to evaluate the clinical effectiveness and cost-effectiveness of a conservative peripheral oxygen saturation (Spo2) target of 88-92% compared with a liberal target of more than 94%. DESIGN: Pragmatic, open, multiple-center, parallel group randomized control trial with integrated economic evaluation. SETTING: Fifteen PICUs across England, Wales, and Scotland. PATIENTS: Infants and children age more than 38 week-corrected gestational age to 16 years who are accepted to a participating PICU as an unplanned admission and receiving invasive mechanical ventilation with supplemental oxygen for abnormal gas exchange. INTERVENTION: Adjustment of ventilation and inspired oxygen settings to achieve an Spo2 target of 88-92% during invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Randomization is 1:1 to a liberal Spo2 target of more than 94% or a conservative Spo2 target of 88-92% (inclusive), using minimization with a random component. Minimization will be performed on: age, site, primary reason for admission, and severity of abnormality of gas exchange. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred to after randomization. The primary clinical outcome is a composite of death and days of organ support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of oxygenation and organ support, and discharge outcomes. This trial received Health Research Authority approval on December 23, 2019 (reference: 272768), including a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee (reference number: 19/EE/0362). Trial findings will be disseminated in national and international conferences and peer-reviewed journals

Organizational characteristics of European pediatric onco-critical care: An international cross-sectional survey

BACKGROUND Intensified treatment protocols have improved survival of pediatric oncology patients. However, these treatment protocols are associated with increased treatment-related morbidity requiring admission to pediatric intensive care unit (PICU). We aimed to describe the organizational characteristics and processes of care for this patient group across PICUs in Europe. METHODS A web-based survey was sent to PICU directors or representative physicians between February and June 2021. RESULTS Responses were obtained from 77 PICUs of 12 European countries. Organizational characteristics were similar across the different countries of Europe. The median number of PICU beds was 12 (IQR 8-16). The majority of the PICUs was staffed by pediatric intensivists and had a 24/7 intensivist coverage. Most PICUs had a nurse-to-patient ratio of 1:1 or 1:2. The median numbers of yearly planned and unplanned PICU admissions of pediatric cancer patients were 20 (IQR 10-45) and 10 (IQR 10-30, respectively. Oncology specific practices within PICU were less common in participating centres. This included implementation of oncology protocols in PICU (30%), daily rounds of PICU physicians on the wards (13%), joint mortality and morbidity meetings or complex patients' discussions (30% and 40%, respectively) and participation of parents during clinical rounds (40%). CONCLUSION Our survey provides an overview on the delivery of critical care for oncology patients in PICU across European countries. Multidisciplinary care for these vulnerable and challenging patients remains complex and challenging. Future studies need to determine the effects of differences in PICU organization and processes of care on patients' outcome

Diabetic foot ulcers segmentation challenge report: benchmark and analysis

Monitoring the healing progress of diabetic foot ulcers is a challenging process. Accurate segmentation of foot ulcers can help podiatrists to quantitatively measure the size of wound regions to assist prediction of healing status. The main challenge in this field is the lack of publicly available manual delineation, which can be time consuming and laborious. Recently, methods based on deep learning have shown excellent results in automatic segmentation of medical images, however, they require large-scale datasets for training, and there is limited consensus on which methods perform the best. The 2022 Diabetic Foot Ulcers segmentation challenge was held in conjunction with the 2022 International Conference on Medical Image Computing and Computer Assisted Intervention, which sought to address these issues and stimulate progress in this research domain. A training set of 2000 images exhibiting diabetic foot ulcers was released with corresponding segmentation ground truth masks. Of the 72 (approved) requests from 47 countries, 26 teams used this data to develop fully automated systems to predict the true segmentation masks on a test set of 2000 images, with the corresponding ground truth segmentation masks kept private. Predictions from participating teams were scored and ranked according to their average Dice similarity coefficient of the ground truth masks and prediction masks. The winning team achieved a Dice of 0.7287 for diabetic foot ulcer segmentation. This challenge has now entered a live leaderboard stage where it serves as a challenging benchmark for diabetic foot ulcer segmentation

Nature: a new paradigm for well-being and ergonomics

Nature is presented as a new paradigm for ergonomics. As a discipline concerned with well-being, the importance of natural environments for wellness should be part of ergonomics knowledge and practice. This position is supported by providing a concise summary of the evidence of the value of the natural environment to well-being. Further, an emerging body of research has found relationships between well-being and a connection to nature, a concept that reveals the integrative character of human experience which can inform wider practice and epistemology in ergonomics. Practitioners are encouraged to bring nature into the workplace, so that ergonomics keeps pace with the move to nature-based solutions, but also as a necessity in the current ecological and social context. Practitioner Summary: Nature-based solutions are coming to the fore to address societal challenges such as well-being. As ergonomics is concerned with well-being, there is a need for a paradigm shift in the discipline. This position is supported by providing a concise summary of the evidence of the value of the natural environment to well-being

CRMP5 Regulates Generation and Survival of Newborn Neurons in Olfactory and Hippocampal Neurogenic Areas of the Adult Mouse Brain

The Collapsin Response Mediator Proteins (CRMPs) are highly expressed in the developing brain, and in adult brain areas that retain neurogenesis, ie: the olfactory bulb (OB) and the dentate gyrus (DG). During brain development, CRMPs are essentially involved in signaling of axon guidance and neurite outgrowth, but their functions in the adult brain remain largely unknown. CRMP5 has been initially identified as the target of auto-antibodies involved in paraneoplasic neurological diseases and further implicated in a neurite outgrowth inhibition mediated by tubulin binding. Interestingly, CRMP5 is also highly expressed in adult brain neurogenic areas where its functions have not yet been elucidated. Here we observed in both neurogenic areas of the adult mouse brain that CRMP5 was present in proliferating and post-mitotic neuroblasts, while they migrate and differentiate into mature neurons. In CRMP5−/− mice, the lack of CRMP5 resulted in a significant increase of proliferation and neurogenesis, but also in an excess of apoptotic death of granule cells in the OB and DG. These findings provide the first evidence that CRMP5 is involved in the generation and survival of newly generated neurons in areas of the adult brain with a high level of activity-dependent neuronal plasticity