Blunted anticipatory stress responses on competition day in team sports athletes compared to individual sports athletes.

Knowledge of anticipatory stress responses before sports competitions is limited, thus this study examined the relationship between anticipatory stress in terms of salivary cortisol secretion in athletes on the morning of a competition and a comparison baseline day. Thirty-seven athletes collected three saliva samples over a 45-min period post-awakening (0, 30 and 45 min). Anticipatory stress was expressed as Area Under the Curve compared to ground (AUCg; total cortisol secretion). There was no significant difference in AUCg between baseline and competition days. However, a mixed two-factor ANOVA with day and sport type (individual vs. team) revealed a significant main effect of sport type (p < 0.01) and a significant interaction (p = 0.001). Individual athletes demonstrated increased AUCg on competition day compared to baseline, while team athletes demonstrated decreased AUCg on competition day compared to baseline. This blunting response was also observed when analysing the raw cortisol secretion levels upon awakening. These findings suggest there may be substantive differences in anticipatory stress between individual and team sport athletes.

Revealing the nature of cardiovascular disease using DERGA, a novel data ensemble refinement greedy algorithm.

BACKGROUND: The study aimed to determine the most crucial parameters associated with CVD and employ a novel data ensemble refinement procedure to uncover the optimal pattern of these parameters that can result in a high prediction accuracy. METHODS AND RESULTS: Data were collected from 369 patients in total, 281 patients with CVD or at risk of developing it, compared to 88 otherwise healthy individuals. Within the group of 281 CVD or at-risk patients, 53 were diagnosed with coronary artery disease (CAD), 16 with end-stage renal disease, 47 newly diagnosed with diabetes mellitus 2 and 92 with chronic inflammatory disorders (21 rheumatoid arthritis, 41 psoriasis, 30 angiitis). The data were analyzed using an artificial intelligence-based algorithm with the primary objective of identifying the optimal pattern of parameters that define CVD. The study highlights the effectiveness of a six-parameter combination in discerning the likelihood of cardiovascular disease using DERGA and Extra Trees algorithms. These parameters, ranked in order of importance, include Platelet-derived Microvesicles (PMV), hypertension, age, smoking, dyslipidemia, and Body Mass Index (BMI). Endothelial and erythrocyte MVs, along with diabetes were the least important predictors. In addition, the highest prediction accuracy achieved is 98.64%. Notably, using PMVs alone yields a 91.32% accuracy, while the optimal model employing all ten parameters, yields a prediction accuracy of 0.9783 (97.83%). CONCLUSIONS: Our research showcases the efficacy of DERGA, an innovative data ensemble refinement greedy algorithm. DERGA accelerates the assessment of an individual's risk of developing CVD, allowing for early diagnosis, significantly reduces the number of required lab tests and optimizes resource utilization. Additionally, it assists in identifying the optimal parameters critical for assessing CVD susceptibility, thereby enhancing our understanding of the underlying mechanisms.

Prognosis of COVID-19 severity using DERGA, a novel machine learning algorithm.

It is important to determine the risk for admission to the intensive care unit (ICU) in patients with COVID-19 presenting at the emergency department. Using artificial neural networks, we propose a new Data Ensemble Refinement Greedy Algorithm (DERGA) based on 15 easily accessible hematological indices. A database of 1596 patients with COVID-19 was used; it was divided into 1257 training datasets (80 % of the database) for training the algorithms and 339 testing datasets (20 % of the database) to check the reliability of the algorithms. The optimal combination of hematological indicators that gives the best prediction consists of only four hematological indicators as follows: neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase, ferritin, and albumin. The best prediction corresponds to a particularly high accuracy of 97.12 %. In conclusion, our novel approach provides a robust model based only on basic hematological parameters for predicting the risk for ICU admission and optimize COVID-19 patient management in the clinical practice.

Genetic justification of COVID-19 patient outcomes using DERGA, a novel data ensemble refinement greedy algorithm.

Complement inhibition has shown promise in various disorders, including COVID-19. A prediction tool including complement genetic variants is vital. This study aims to identify crucial complement-related variants and determine an optimal pattern for accurate disease outcome prediction. Genetic data from 204 COVID-19 patients hospitalized between April 2020 and April 2021 at three referral centres were analysed using an artificial intelligence-based algorithm to predict disease outcome (ICU vs. non-ICU admission). A recently introduced alpha-index identified the 30 most predictive genetic variants. DERGA algorithm, which employs multiple classification algorithms, determined the optimal pattern of these key variants, resulting in 97% accuracy for predicting disease outcome. Individual variations ranged from 40 to 161 variants per patient, with 977 total variants detected. This study demonstrates the utility of alpha-index in ranking a substantial number of genetic variants. This approach enables the implementation of well-established classification algorithms that effectively determine the relevance of genetic variants in predicting outcomes with high accuracy.

Early prediction of COVID-19 outcome using artificial intelligence techniques and only five laboratory indices.

We aimed to develop a prediction model for intensive care unit (ICU) hospitalization of Coronavirus disease-19 (COVID-19) patients using artificial neural networks (ANN). We assessed 25 laboratory parameters at first from 248 consecutive adult COVID-19 patients for database creation, training, and development of ANN models. We developed a new alpha-index to assess association of each parameter with outcome. We used 166 records for training of computational simulations (training), 41 for documentation of computational simulations (validation), and 41 for reliability check of computational simulations (testing). The first five laboratory indices ranked by importance were Neutrophil-to-lymphocyte ratio, Lactate Dehydrogenase, Fibrinogen, Albumin, and D-Dimers. The best ANN based on these indices achieved accuracy 95.97%, precision 90.63%, sensitivity 93.55%. and F1-score 92.06%, verified in the validation cohort. Our preliminary findings reveal for the first time an ANN to predict ICU hospitalization accurately and early, using only 5 easily accessible laboratory indices.

Effect of standing frames used in real life on bone remodeling in non-walking children with cerebral palsy.

Children with severe cerebral palsy are prone to low bone mineral density. No clear recommendation exists for an optimal use of standing frame to enhance bone health in this context. Used in real life, this study suggests for the first time that standing practice improved bone mineralization by limiting bone resorption. INTRODUCTION: To compare the bone health of children with severe cerebral palsy who use a static standing frame in real life to that of children who do not. METHODS: A total of 24 children with severe cerebral palsy GMFCS IV & V were included in the study and were divided into two groups: 13 were using a passive standing frame and 11 were not. We performed a single center retrospective cross-sectional study comparing the two groups using dual X-ray absorptiometry data and tests on biological samples, including bone remodeling factors. RESULTS: Total body (less head) bone mineral content was significantly higher in children who used a standing frame for an average of 30 min/day. This was confirmed in the lumbar spine. Although the total body bone mineral density (less head and proximal femur) densitometric data were not significantly higher, a positive trend favored the use of a standing frame in the children. Bone resorptive factors (CTX) were higher in the non-standing-frame group, whereas there was no difference among osteoformation factors. No difference in fracture history was found. CONCLUSIONS: We show that non-ambulant children with cerebral palsy who use a static standing frame in real life have better bone health, with lower bone resorption, than children who do not. Further studies are needed to determine how standing practice could impact bone mineralization over time in real life and to explore more bone remodeling factors.

Lumbar zygapophyseal joints injections under ultrasound guidance an alternative to fluoroscopy guidance in the management of low back pain.

Ultrasound-guided injections are an alternative to evaluate in the management of low back pain associated with osteoarthritis of the lumbar facet joints: it eliminates the risk of ionizing radiation for both the patient and the practitioner. This study aims to compare the short-term clinical efficacy of lumbar facet joints injections between ultrasound-guided injections and fluoroscopy-guided injections. Observational, retrospective, single-center study. Patients received one or two lumbar zygapophyseal joints injections under fluoroscopy or ultrasound and a follow-up consultation at one month. Data from 54 patients was collected. The median of the evolution of VAS at one month was - 30 mm [-50.0; -20.0] in the ultrasound group and - 29.5 mm [-47.0; -15.0] (p < 0.001) in the fluoroscopy group with no statistically significant difference between the two groups (p = 0.835). There were no injection-related complications in either group during the follow-up. The percentage of patients who stopped NSAIDs was not statistically significant between the two groups (p = 1.00). Injections of corticosteroids of lumbar facet joints under ultrasound guidance significantly reduced pain after one month, with no difference found between the two techniques. Ultrasound-guided injections are reliable, accessible and a safe alternative that should be preferred over those under fluoroscopy.

Genetic prediction of ICU hospitalization and mortality in COVID-19 patients using artificial neural networks.

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID-19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID-19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID-19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype.

Genetic justification of severe COVID-19 using a rigorous algorithm.

Recent studies suggest excessive complement activation in severe coronavirus disease-19 (COVID-19). The latter shares common characteristics with complement-mediated thrombotic microangiopathy (TMA). We hypothesized that genetic susceptibility would be evident in patients with severe COVID-19 (similar to TMA) and associated with disease severity. We analyzed genetic and clinical data from 97 patients hospitalized for COVID-19. Through targeted next-generation-sequencing we found an ADAMTS13 variant in 49 patients, along with two risk factor variants (C3, 21 patients; CFH,34 patients). 31 (32%) patients had a combination of these, which was independently associated with ICU hospitalization (p = 0.022). Analysis of almost infinite variant combinations showed that patients with rs1042580 in thrombomodulin and without rs800292 in complement factor H did not require ICU hospitalization. We also observed gender differences in ADAMTS13 and complement-related variants. In light of encouraging results by complement inhibitors, our study highlights a patient population that might benefit from early initiation of specific treatment.

Necrotizing fasciitis and the midterm outcomes after survival.

BACKGROUND AND AIMS: Radical surgical intervention is necessary to save patients' lives in cases of necrotizing fasciitis. This leads to persistent disabilities and most likely to a deteriorated quality of life. The purpose of this study was to evaluate the midterm outcomes after survival of necrotizing fasciitis. MATERIALS AND METHODS: A retrospective analysis of 69 patients, treated for necrotizing fasciitis between 2003 and 2012. The patients were identified using the International Classification of Diseases (10th Revision) code M 72.6. Of the 50 survivors, 22 patients completed the Short Form 36 and Short Musculoskeletal Function Assessment questionnaires as a postal survey. The follow-up averaged 59 months (range: 6-128 months). RESULTS: The average age at the time of necrotizing fasciitis was 60.0 years. The body mass index average was 29.7. The patients had a significantly decreased physical component summary score of 33.3 compared to a normative group (p < 0.001) (Short Form 36). They further showed a significantly decreased dysfunction and bother indices (Short Musculoskeletal Function Assessment) (p < 0.001). An increased age (⩾70 years) was associated with an inferior role emotional (p = 0.048) and physical functioning (p = 0.011) as well as social functioning (p = 0.038) (Short Form 36). The majority of patients (16, 72.7%) complained of pain at the final follow-up and 50% of patients required an assistive device on a regular basis. CONCLUSION: Patients who survived necrotizing fasciitis suffer from functional impairment and changed body appearance. Assistive devices or pain medication are often required, and the patients present with significantly decreased physical, social, and emotional functioning at the midterm follow-up. The patient's age is a critical factor regarding functional or mental outcome parameters. Further research on the post-hospital course and long-term multidisciplinary care is required to improve the outcomes of these patients.

Molecular and epidemiological evidence of patient-to-patient hepatitis C virus transmission in a Scottish emergency department.

BACKGROUND: Transmission of hepatitis C virus (HCV) in the healthcare setting is rare. Routine infection prevention and control measures mean that this should be a preventable 'never event'. AIM: To investigate the diagnosis of acute healthcare-associated HCV infection. METHODS: Epidemiological and molecular investigation of a case of acute HCV infection associated with nosocomial exposure. FINDINGS: Detailed investigation of the treatment history of a patient with acute HCV infection identified transmission from a co-attending patient in an emergency department as the likely source; this possibility was confirmed by virus sequence analysis. The precise route of transmission was not identified, though both patient and source had minimally invasive healthcare interventions. Review of infection, prevention and control identified potentially contributory factors in the causal pathway including hand hygiene, inappropriate use of personal protective equipment, and blood contamination of the surface of the departmental blood gas analyser. CONCLUSION: We provide molecular and epidemiological evidence of HCV transmission between patients in an emergency department that was made possible by environmental contamination. Patients with HCV infection are higher users of emergency care than the general population and a significant proportion of those affected remain unknown and/or infectious. Equipment, departmental design, staff behaviour, and patient risk require regular review to minimize the risk of nosocomial HCV transmission.

The Scottish enhanced Staphylococcus aureus bacteraemia surveillance programme: the first 18 months of data in adults.

BACKGROUND: Staphylococcus aureus bacteraemia (SAB) is the second most common source of positive blood cultures, after Escherichia coli, reported within NHS Scotland. Laboratory surveillance has been mandatory in Scotland for SAB since 2001. AIM: To gain an understanding of the epidemiology of SAB cases and associated risk factors for healthcare and true community onset. Identification of these factors and the patient populations at greatest risk enables the development of focused improvement plans. METHODS: All NHS boards within NHS Scotland take part in the mandatory enhanced surveillance, with data collected by trained data collectors using nationally agreed definitions. FINDINGS: Between 1st October 2014 and 31st March 2016, 2256 episodes of SAB in adults were identified. The blood cultures were taken in 58 hospitals and across all 15 Scottish health boards. The data demonstrated that approximately one-third of all SAB cases are true community cases. Vascular access devices continue to be the most reported entry point (25.7%) in individuals who receive health care, whereas skin and soft tissue risk factors are present in all origins. A significant risk factor unique to community cases is illicit drug injection. CONCLUSION: Improvement plans for reduction of SAB should be targeted more widely than hospital care settings alone.

The Scottish enhanced Staphylococcus aureus bacteraemia surveillance programme: the first 18 months of data in children.

BACKGROUND: National enhanced surveillance of Staphylococcus aureus bacteraemia (SAB) commenced on 1st October 2014 to gain a more in-depth understanding of the epidemiology of SAB in Scotland. Children under 16 years of age were analysed separately from adults because previous studies had demonstrated epidemiological differences. AIM: To identify risk factors and patient populations at greatest risk to enable the development of focused improvement plans. METHODS: All National Health Service (NHS) boards within NHS Scotland take part in the mandatory enhanced surveillance, with data collected by trained data collectors using nationally agreed definitions. FINDINGS: Analysis of the first 18 months of data showed that hospital-acquired SAB was mostly associated with neonates with device risk factors, whereas community-associated SAB was found in older children who had few, if any, risk factors and most presented with a bone or joint infection. CONCLUSION: The enhanced SAB data highlighted the difference in risk factors and entry points for the acquisition of SAB within the paediatric population.

Lessons learned from a prolonged and costly norovirus outbreak at a Scottish medicine of the elderly hospital: case study.

BACKGROUND: Norovirus outbreaks are a major burden for healthcare facilities globally. AIM: Lessons learned to inform an action plan to improve facilities as well as responses to norovirus within the medicine of the elderly (MoE) hospital as well as other NHS (National Health Service) Lothian facilities. METHODS: This study investigated the impact of a prolonged outbreak at an MoE hospital in one of the 14 Scottish health boards between February and March 2013. FINDINGS: In all, 143 patients (14.80 cases per 1000 inpatient bed-days) and 30 healthcare staff (3.10 cases per 1000 inpatient bed-days) were affected clinically and 63 patients were confirmed virologically. Restricting new admissions to affected units resulted in 1192 lost bed-days. The cost due to lost bed-days in addition to staff absence and management of the outbreak was estimated at £341,534 for this incident alone. At certain points during the outbreak, the whole facility was closed with resulting major impact on the health board's acute care hospitals. CONCLUSION: Due to the outbreak, new measures were implemented for the first time within NHS Lothian that included floor-by-floor (instead of individual) ward closures, enhanced cleaning with chlorine-based products throughout the hospital, reduction in bed capacity with enhanced bed-spacing and interruption to direct admissions from the Board's general practice surgeries, and temporary suspension of visitors to affected areas. Together with regular communication to staff, patients, relatives, and the public throughout the outbreak and good engagement of staff groups in management of the incident, the outbreak was gradually brought under control.

Imaging the lipid-phase-dependent pore formation of equinatoxin II in droplet interface bilayers.

Using phase-separated droplet interface bilayers, we observe membrane binding and pore formation of a eukaryotic cytolysin, Equinatoxin II (EqtII). EqtII activity is known to depend on the presence of sphingomyelin in the target membrane and is enhanced by lipid phase separation. By imaging the ionic flux through individual pores in vitro, we observe that EqtII pores form predominantly within the liquid-disordered phase. We observe preferential binding of labeled EqtII at liquid-ordered/liquid-disordered domain boundaries before it accumulates in the liquid-disordered phase.

A bio-inspired spatial patterning circuit.

Lateral Inhibition (LI) is a widely conserved patterning mechanism in biological systems across species. Distinct from better-known Turing patterns, LI depend on cell-cell contact rather than diffusion. We built an in silico genetic circuit model to analyze the dynamic properties of LI. The model revealed that LI amplifies differences between neighboring cells to push them into opposite states, hence forming stable 2-D patterns. Inspired by this insight, we designed and implemented an electronic circuit that recapitulates LI patterning dynamics. This biomimetic system serve as a physical model to elucidate the design principle of generating robust patterning through spatial feedback, regardless of the underlying devices being biological or electrical.

Molecular epidemiology of norovirus in Edinburgh healthcare facilities, Scotland 2007-2011.

Norovirus (NoV) is a leading cause of outbreaks of gastroenteritis worldwide, and a major burden for healthcare facilities. This study investigated the NoV genotypes responsible for outbreaks in Edinburgh healthcare facilities between June 2008 and July 2011, and studied their temporal distribution to enable a better understanding of the epidemiology of the outbreaks. A total of 287 samples positive for NoV genogroup II (GII) RNA by reverse transcription-polymerase chain reaction (RT-PCR) during routine diagnostic testing were investigated. Nested RT-PCR (nRT-PCR) and sequencing was used to genotype the NoV strains. Overall, a total of 69 NoV strains belonging to six different genoclusters (GII.1, GII.2, GII.3, GII.4, GII.6, GII.13) were detected. The predominant genotype was GII.4 that included four variants, GII.4 2006a, GII.4 2006b, GII.4 2007 and GII.4 2010. Importantly, increases in NoV activity coincided with the emergence of new GII.4 strains, highlighting the need for an active surveillance system to allow the rapid identification of new strains.

Epidemiology and costs associated with norovirus outbreaks in NHS Lothian, Scotland 2007-2009.

Healthcare-associated gastroenteritis outbreaks are becoming more common and are recognized challenges in hospital and community settings. In Edinburgh [NHS (National Health Service) Lothian], all the hospitals and the community were actively monitored for outbreaks of gastroenteritis from September 2007 to June 2009. In total, 1732 patients and 599 healthcare staff were affected in 192 unit outbreaks. In the acute sector, 1368 patients (0.99 cases/1000 inpatient bed-days) and 406 healthcare staff (0.29 cases/1000 inpatient bed-days) were affected in 155 unit outbreaks (0.23 unit outbreaks/day). Noroviruses were detected in 142 outbreaks (74%); 50 were not laboratory confirmed but were presumed to be noroviruses on epidemiological grounds. The closure of affected units to new admissions resulted in the loss of 3678 bed-days. By extrapolation, lost bed-days and staff absence due to gastroenteritis outbreaks cost NHS Lothian £1.2 million for the two norovirus seasons. Outbreaks in which the affected unit was closed within the first three days of recognizing the index case were contained in a mean of six days, and outbreaks in units that were closed later persisted for a mean of seven days; this difference was not statistically significant. Rapid implementation of control measures was effective in the control of outbreaks.

Real-time evaluation of an optimized real-time PCR assay versus Brilliance chromogenic MRSA agar for the detection of meticillin-resistant Staphylococcus aureus from clinical specimens.

A total of 1204 meticillin-resistant Staphylococcus aureus (MRSA) screens (3340 individual swabs) were tested to evaluate a staphylococcal cassette chromosome mec (SCCmec) real-time PCR. In total, 148 (12.3 %) of the screens were MRSA-positive, where 146 (12.1 %) were MRSA-positive by the SCCmec real-time PCR assay. In contrast, 128 (10.6 %) screens were MRSA-positive by culture. One hundred and twenty-six (10.5 %) of the screens were positive by both culture and PCR. Twenty of the 1204 screens (1.66 %) were negative by culture but positive by PCR; these samples were sequenced. In 14 of the cases, a homology search confirmed the sequence as SCCmec, indicating that these samples could be considered true positives. Two of the 1204 (0.2 %) screens were positive by culture and negative by PCR. The mean turnaround time (TAT) for PCR-negative swabs was 6 h 12 min and for PCR-positive swabs was 6 h 48 min. In comparison, for culture-negative swabs the mean TAT was 29 h 30 min and for culture-positive swabs was 69 h. The cost per swab for routine culture was £0.41 (€0.48) and that of the real-time PCR assay was £2.35 (€2.75). This optimized, in-house, inexpensive, real-time PCR test maintained a very high sensitivity and specificity when evaluated under real-time laboratory conditions. The TAT of this real-time PCR assay was substantially lower than that of chromogenic culture. It was also maintained throughout the entire process, which can be taken as an indirect measure of test performance. This study showed that implementation of a molecular test can be achieved with limited resources in a standard microbiology laboratory.

Comparison of two multilocus variable-number tandem-repeat methods and pulsed-field gel electrophoresis for differentiating highly clonal methicillin-resistant Staphylococcus aureus isolates.

In the United Kingdom, EMRSA-15 and EMRSA-16 account for the majority (∼90%) of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infections. Currently, the standard typing technique, pulsed-field gel electrophoresis (PFGE), is laborious and insufficient for discriminating between closely related subtypes of EMRSA-15 and -16. The objective of the present study was to compare the usefulness of multilocus variable-number tandem-repeat fingerprinting (MLVF) and multilocus variable-number tandem-repeat analysis (MLVA) with PFGE for subtyping these highly clonal MRSA lineages. A panel of 85 MRSA isolates (41 EMRSA-15, 20 EMRSA-16, and 24 MRSA isolates with diverse PFGE patterns) was investigated. In addition, a further 29 EMRSA-15s with identical PFGE patterns from two geographically linked but epidemiologically distinct outbreaks and several sporadic cases were analyzed. PFGE, MLVF, and MLVA resolved 66 (Simpson's index of diversity [SID] = 0.984), 51 (SID = 0.95), and 42 (SID = 0.881) types, respectively, among the 85 MRSA isolates. MLVF was more discriminatory than MLVA for EMRSA-15 and -16 strains, but both methods had comparable discriminatory powers for distinguishing isolates in the group containing diverse PFGE types. MLVF was comparable to PFGE for resolving the EMRSA-15s but had a lower discriminatory power for the EMRSA-16s. MLVF and MLVA resolved the 29 isolates with identical PFGE patterns into seven and six subtypes, respectively. Importantly, both assays indicated that the two geographically related outbreaks were caused by distinct subtypes of EMRSA-15. Taken together, the data suggest that both methods are suitable for identifying and tracking specific subtypes of otherwise-indistinguishable MRSA. However, due to its greater discriminatory power, MLVF would be the most suitable alternative to PFGE for hospital outbreak investigations.