The persistence of coronavirus disease 2019 (COVID-19)-related hospitalization severely threatens medical systems worldwide and has increased the need for reliable detection of acute status and prediction of mortality. We applied a systems biology approach to discover acute-stage biomarkers that could predict mortality. A total 247 plasma samples were collected from 103 COVID-19 (52 surviving COVID-19 patients and 51 COVID-19 patients with mortality), 51 patients with other infectious diseases (IDCs) and 41 healthy controls (HCs). Paired plasma samples were obtained from survival COVID-19 patients within 1 day after hospital admission and 1-3 days before discharge. There were clear differences between COVID-19 patients and controls, as well as substantial differences between the acute and recovery phases of COVID-19. Samples from patients in the acute phase showed suppressed immunity and decreased steroid hormone biosynthesis, as well as elevated inflammation and proteasome activation. These findings were validated by enzyme-linked immunosorbent assays and metabolomic analyses in a larger cohort. Moreover, excessive proteasome activity was a prominent signature in the acute phase among patients with mortality, indicating that it may be a key cause of poor prognosis. Based on these features, we constructed a machine learning panel, including four proteins [C-reactive protein (CRP), proteasome subunit alpha type (PSMA)1, PSMA7, and proteasome subunit beta type (PSMB)1)] and one metabolite (urocortisone), to predict mortality among COVID-19 patients (area under the receiver operating characteristic curve: 0.976) on the first day of hospitalization. Our systematic analysis provides a novel method for the early prediction of mortality in hospitalized COVID-19 patients.

C-reactive protein (CRP) is a plasma protein that is evolutionarily conserved, found in both vertebrates and many invertebrates. It is a member of the pentraxin superfamily, characterized by its pentameric structure and calcium-dependent binding to ligands like phosphocholine (PC). In humans and various other species, the plasma concentration of this protein is markedly elevated during inflammatory conditions, establishing it as a prototypical acute phase protein that plays a role in innate immune responses. This feature can also be used clinically to evaluate the severity of inflammation in the organism. Human CRP (huCRP) can exhibit contrasting biological functions due to conformational transitions, while CRP in various species retains conserved protective functions in vivo. The focus of this review will be on the structural traits of CRP, the regulation of its expression, activate complement, and its function in related diseases in vivo.

UNASSIGNED: To synthesize evidence on the effect of early post-stroke spasticity interventions.
UNASSIGNED: Systematic literature search (PubMed, Embase, and Web of Science) encompassing studies on spasticity reducing interventions within 3 months post stroke on outcome defined within the International Classification of Functioning (ICF).
UNASSIGNED: In total, 27 studies were identified with n = 1.658 cases. Botulinum toxin (2-12 weeks; 10 studies, n = 794) showed consistent and significant reduced spasticity by Modified Ashworth Scale (MAS) or electromyography (EMG). Electrical muscle stimulation (1-8 weeks; 6 studies, n = 335) showed lower MAS/Composite Spasticity Scale scores in 4 studies. Transcranial stimulation (3 studies; n = 131), oral spasmolytics (1 study; n = 38), shockwave (1 study; n = 40), orthotics (3 studies; n = 197 and robot-assisted therapy (3 studies; n = 123) showed inconclusive results. Effects on ICF activity domain could not be established due to limited data and large outcome measures heterogeneity. One out of two studies showed significant benefit for early compared to late BoNT intervention (< 90 vs> 90 days).
UNASSIGNED: This study provides evidence for early applied (<3 months) BoNT to effectively reduce spasticity and probable effectiveness of electrical stimulation. Establishing effects of interventions in the acute/hospitalization phase (<7 days) needs further work, specifically on the ICF activity domain. Standardization of outcome measures is required.
Spasticity, which may develop in the first weeks after stroke, is now mostly treated in the chronic phase.This study shows that early applied Botulinum Toxin (within three months after stroke) effectively reduces spasticity and suggests that electrical stimulation may reduce spasticity.Early application of treatment with Botulinum Toxin should be considered when spasticity occurs within three months post-stroke.

OBJECTIVE: To review the literature on the topic, to suggest a common line of treatment applicable across a wide community of specialists, and to contribute in maintaining the high level of interest in this disease.
METHODS: A comprehensive and exhaustive review of the literature was performed, identifying hundreds of articles on the topic.
RESULTS: Peyronie\'s disease is a condition that has been recognized, studied, and treated for centuries; despite this, if one excludes surgery in cases in which the deformity is stable, no clear treatment (or line of treatment) is available for complete relief of signs and symptoms. Treatment options were divided into local, oral, and injection therapy, and a wide variety of drugs, remedies, and options were identified.
CONCLUSIONS: Low-intensity extracorporeal shock wave therapy, vacuum therapy, penile traction therapy, phosphodiesterase type 5 inhibitors, hyaluronic acid, and collagenase of Clostridium histolyticum may be recommended only in specific contexts. Further studies on individual options or potential combinations are required.

Introduction: Diving decompression theory hypothesizes inflammatory processes as a source of micronuclei which could increase related risks. Therefore, we tested 10 healthy, male divers. They performed 6-8 dives with a maximum of two dives per day at depths ranging from 21 to 122 msw with CCR mixed gas diving. Methods: Post-dive VGE were counted by echocardiography. Saliva and urine samples were taken before and after each dive to evaluate inflammation: ROS production, lipid peroxidation (8-iso-PGF2), DNA damage (8-OH-dG), cytokines (TNF-α, IL-6, and neopterin). Results: VGE exhibits a progressive reduction followed by an increase (p < 0.0001) which parallels inflammation responses. Indeed, ROS, 8-iso-PGF2, IL-6 and neopterin increases from 0.19 ± 0.02 to 1.13 ± 0.09 μmol.min-1 (p < 0.001); 199.8 ± 55.9 to 632.7 ± 73.3 ng.mg-1 creatinine (p < 0.0001); 2.35 ± 0.54 to 19.5 ± 2.96 pg.mL-1 (p < 0.001); and 93.7 ± 11.2 to 299 ± 25.9 μmol·mol-1 creatinine (p = 0.005), respectively. The variation after each dive was held constant around 158.3% ± 6.9% (p = 0.021); 151.4% ± 5.7% (p < 0.0001); 176.3% ± 11.9% (p < 0.0001); and 160.1% ± 5.6% (p < 0.001), respectively. Discussion: When oxy-inflammation reaches a certain level, it exceeds hormetic coping mechanisms allowing second-generation micronuclei substantiated by an increase of VGE after an initial continuous decrease consistent with a depletion of \"first generation\" pre-existing micronuclei.

BACKGROUND: Severe burns may alter the stability of the intestinal flora and affect the patient\'s recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association with phenotype can help to accurately assess the progression of the disease and identify potential microbiota markers.
METHODS: We established mouse models of partial thickness deep III degree burns and collected faecal samples for 16 S rRNA amplification and high throughput sequencing at two time points in the acute phase for independent bioinformatic analysis.
RESULTS: We analysed the sequencing results using alpha diversity, beta diversity and machine learning methods. At both time points, 4 and 6 h after burning, the Firmicutes phylum content decreased and the content of the Bacteroidetes phylum content increased, showing a significant decrease in the Firmicutes/Bacteroidetes ratio compared to the control group. Nine bacterial genera changed significantly during the acute phase and occupied the top six positions in the Random Forest significance ranking. Clustering results also clearly showed that there was a clear boundary between the communities of burned and control mice. Functional analyses showed that during the acute phase of burn, gut bacteria increased lipoic acid metabolism, seleno-compound metabolism, TCA cycling, and carbon fixation, while decreasing galactose metabolism and triglyceride metabolism. Based on the abundance characteristics of the six significantly different bacterial genera, both the XGboost and Random Forest models were able to discriminate between the burn and control groups with 100% accuracy, while both the Random Forest and Support Vector Machine models were able to classify samples from the 4-hour and 6-hour burn groups with 86.7% accuracy.
CONCLUSIONS: Our study shows an increase in gut microbiota diversity in the acute phase of deep burn injury, rather than a decrease as is commonly believed. Severe burns result in a severe imbalance of the gut flora, with a decrease in probiotics and an increase in microorganisms that trigger inflammation and cognitive deficits, and multiple pathways of metabolism and substance synthesis are affected. Simple machine learning model testing suggests several bacterial genera as potential biomarkers of severe burn phenotypes.

Antimicrobial usage (AMU) could be reduced by differentiating the causative bacteria in cases of clinical mastitis (CM) as either Gram-positive or Gram-negative bacteria or identifying whether the case is culture-negative (no growth, NG) mastitis. Immunoassays for biomarker analysis and a Tandem Mass Tag (TMT) proteomic investigation were employed to identify differences between samples of milk from cows with CM caused by different bacteria. A total of 94 milk samples were collected from cows diagnosed with CM across seven farms in Scotland, categorized by severity as mild (score 1), moderate (score 2), or severe (score 3). Bovine haptoglobin (Hp), milk amyloid A (MAA), C-reactive protein (CRP), lactoferrin (LF), α-lactalbumin (LA) and cathelicidin (CATHL) were significantly higher in milk from cows with CM, regardless of culture results, than in milk from healthy cows (all P-values <0.001). Milk cathelicidin (CATHL) was evaluated using a novel ELISA technique that utilises an antibody to a peptide sequence of SSEANLYRLLELD (aa49-61) common to CATHL 1-7 isoforms. A classification tree was fitted on the six biomarkers to predict Gram-positive bacteria within mastitis severity scores 1 or 2, revealing that compared to the rest of the samples, Gram-positive samples were associated with CRP < 9.5 μg/ml and LF ≥ 325 μg/ml and MAA < 16 μg/ml. Sensitivity of the tree model was 64%, the specificity was 91%, and the overall misclassification rate was 18%. The area under the ROC curve for this tree model was 0.836 (95% bootstrap confidence interval: 0.742; 0.917). TMT proteomic analysis revealed little difference between the groups in protein abundance when the three groups (Gram-positive, Gram-negative and no growth) were compared, however when each group was compared against the entirety of the remaining samples, 28 differentially abundant protein were identified including β-lactoglobulin and ribonuclease. Whilst further research is required to draw together and refine a suitable biomarker panel and diagnostic algorithm for differentiating Gram- positive/negative and NG CM, these results have highlighted a potential panel and diagnostic decision tree. Host-derived milk biomarkers offer significant potential to refine and reduce AMU and circumvent the many challenges associated with microbiological culture, both within the lab and on the farm, while providing the added benefit of reducing turnaround time from 14 to 16 h of microbiological culture to just 15 min with a lateral flow device (LFD).

UNASSIGNED: In the acute phase after a spinal cord injury or disease (SCI/D), various therapeutic assessments and interventions are applied with the goal of restoring structures, preventing complications and preparing the patient as best as possible for further activity and finally participation. The goal was to identify and evaluate the available evidence on assessments and interventions for body functions and structures to prepare adults with acute spinal cord SCI/D for activity and participation during the first 14 days.
UNASSIGNED: A scoping review was conducted. The search was performed on June 19, 2023 using the databases PubMed, PEDro, Cochrane library and Embase. These were screened for studies including patients with acute SCI/D and physiotherapeutic or occupational therapy assessments and interventions. Only studies in English or German published between 2012 and 2023 were included.
UNASSIGNED: Twelve publications met the inclusion criteria, namely three systematic reviews, two randomized controlled trials, two observational studies and five clinical practice guidelines. Assessments as the Spinal Cord Independence Measure, as well as exercises such as daily passive mobilization of body structures against contractures were used in the entire population, while others were only applied in subgroups of SCI/D such as the Graded Redefined Assessment of Strength, Sensation and Prehension or functional electrical stimulation with and without additional movements. The methodological quality of the studies found varied greatly from good to very poor.
UNASSIGNED: Heterogeneity in research design and study population as well as lack of high-quality studies do not cover the standard of clinical management in the acute phase and further comprehensive research is needed.

UNASSIGNED: Suicides are predicted to drop in the acute phase of any crisis that poses a threat to the entire population, though data on this are inconsistent. A pandemic is the most severe global crisis one can imagine. There is an urgent need to identify objective trends in suicide rates across countries and populations in a real-time manner in order to be better informed regarding prospects and adaptation of preventive strategies.
UNASSIGNED: To evaluate suicidal behaviour in a metropolis immediately after the introduction of severe containment measures due to the pandemic.
UNASSIGNED: Cases of completed suicides in St. Petersburg were obtained from the local city Bureau of Forensic Medical Examinations for the period 1 January 2016 to 31 July 2020. Data were accurately collected and monthly frequencies per 100,000 of the population in April-May 2020 (introduction of the most severe stay at home measures) were compared with corresponding data from 2016-2019. Confidence intervals were calculated according to Wilson.
UNASSIGNED: Suicide frequencies in the population of St. Petersburg in April 2020 did not go up, in contrast, they were 30.3% lower than the average for the previous four years. The decrease in April was more pronounced in males than in females (36.3% and12.4%, respectively). When looking at age groups it was found that the biggest drop in suicides was in older males ( 55 years). In this group, suicide indices were 58.5% lower than average for the previous four years. However, in females, there was a 50% rise in suicides in June, while in young males (15-34 years) there was an 87.9% rise in May. Total number of suicides for the first half of 2020 was very close to the average seen in previous years. None of the registered changes were statistically significant.
UNASSIGNED: The analysis is preliminary and does not account for possible seasonality, however, we consider that the reduction in completed suicides immediately after crisis exposure deserves attention. It supports views that in the acute phase of the crisis, suicidal behaviour may decline, which may be quickly replaced by a rise. Such a rise in females and younger males points on possible risk groups and requires a response from society. More studies are needed to have a clearer picture of suicide dynamics in Russia during the different waves of the pandemic, and prevention should be prioritized regardless of the tendencies.

UNASSIGNED: Molecular mechanisms underlying perioperative acute phase reactions in cardiac surgery are largely unknown. We aimed to characterise perioperative alterations of the acute phase plasma proteome in a cohort of adult patients undergoing on-pump cardiac surgery using high-throughput mass spectrometry and to identify candidate proteins potentially relevant to postoperative clinical outcome through a novel, multi-step approach.
UNASSIGNED: This study is an analysis of the Bern Perioperative Biobank, a prospective cohort of adults who underwent cardiac surgery with the use of cardiopulmonary bypass (CPB) at Bern University Hospital between January and December 2019. Blood samples were taken before induction of anaesthesia and on postoperative day one. Proteomic analyses were performed by mass spectrometry. Through a multi-step, exploratory approach, hit-proteins were first identified according to their perioperative prevalence and dynamics. The set of hit-proteins were associated with predefined clinical outcome measures (all-cause one-year mortality, length of hospital stay, postoperative myocardial infarction and stroke until hospital discharge).
UNASSIGNED: 192 patients [75.5% male, median age 67.0 (IQR 60.0-73.0)] undergoing cardiac surgery with the use of CPB were included in this analysis. In total, we identified and quantified 402 proteins across all samples, whereof 30/402 (7%) proteins were identified as hit-proteins. Three hit-proteins-LDHB, VCAM1 and IGFBP2-demonstrated the strongest associations with clinical outcomes. After adjustment both for age, sex, BMI and for multiple comparisons, the scaled preoperative levels of IGFBP2 were associated with 1-year all-cause mortality (OR 10.63; 95% CI: 2.93-64.00; p = 0.046). Additionally, scaled preoperative levels of LDHB (OR 5.58; 95% CI: 2.58-8.57; p = 0.009) and VCAM1 (OR 2.32; 95% CI: 0.88-3.77; p = 0.05) were found to be associated with length of hospital stay.
UNASSIGNED: We identified a subset of promising candidate plasma proteins relevant to outcome after on-pump cardiac surgery. IGFBP2 showed a strong association with clinical outcome measures and a significant association of preoperative levels with 1-year all-cause mortality. Other proteins strongly associated with outcome were LDHB and VCAM1, reflecting the dynamics in the acute phase response, inflammation and myocardial injury. We recommend further investigation of these proteins as potential outcome markers after cardiac surgery.
UNASSIGNED: ClinicalTrials.gov; NCT04767685, data are available via ProteomeXchange with identifier PXD046496.