Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with septic cardiomyopathy being a common and severe complication. Despite its significant clinical impact, the molecular mechanisms underlying sepsis-induced cardiomyopathy (SICM) remain incompletely understood. In this study, we performed a comparative analysis of whole transcriptome profiles in two widely used mouse models of septic cardiomyopathy, the cecal ligation and puncture (CLP) model and the lipopolysaccharide (LPS) model. Our aim was to identify key genes and pathways involved in the development of septic cardiomyopathy and to evaluate the similarities and differences between the two models. Our findings suggested that 1) both methods can induce septic heart dysfunction within 24 hours; 2) distinct whole transcriptome expression profiles are revealed; 3) potentially different pathways are involved in causing heart failure in sepsis. The comprehensive comparison provides valuable insights into the molecular basis of septic cardiomyopathy and contributes to the ongoing search for effective treatment strategies, triggered by different factors for SICM.

Introduction the outbreak of the Israel-Gaza conflict, initiated by a major attack on the civilian population in Israel provided a tragic opportunity to study the community wide association between severe emotional stressors related to acts of war and the incidence and clinical characteristics of Takotsubo cardiomyopathy (TCM) in this scenario. Methods Eight consecutive cases of TCM diagnosed during the first 50 days of the Israel-Gaza conflict were retrospectively collected from two southern medical centers who provided care to most of the war victims throughout the period of monitoring. The medical records were thoroughly reviewed and analyzed. Results During the monitoring period, the incidence of TCM increased substantially compared to the control period. Eight patients were included in the analysis. All patients were female and 100% of patients presented within the first 3 weeks of conflict whereas after this initial phase, despite the continuing war, the incidence of TCM reverted to pre-conflict levels. Two patients (25%) were under 50 years of age. All patients had hazardous clinical characteristics including severe left ventricular (LV) dysfunction (≤35%) and prolonged QTc interval (>500 ms). Five patients (62.5%) experienced complications. Nevertheless, no in-hospital mortality was reported. Conclusions Repeated exposure to severe emotional stress, on both personal and national level, due to mass crisis such as war is associated with an increased incidence of TCM potentially with high-risk phenotype in comparison to TCM following other, less potent, psychological insults.

Myocardial deformation imaging (strain imaging) is a technique to directly quantify the extent of myocardial contractility and overcomes several of the limitations of ejection fraction. The application of the most commonly used strain imaging method; speckle-tracking echocardiography to patients with sepsis cardiomyopathy heralds an exciting development to the field. However; the body of evidence and knowledge on the utility, feasibility and prognostic value of left ventricular global longitudinal strain in sepsis cardiomyopathy is still evolving. We conducted a review of literature on utility of left ventricular global longitudinal strain in sepsis cardiomyopathy. We discuss the role of left ventricular global longitudinal strain in mortality prediction, utility and limitations of the technique in the context of sepsis cardiomyopathy.

Background: Neonatal sepsis associated with severe morbidity and mortality defines the systemic condition arising from the bacterial, viral, fungal origin associated with hemodynamic and clinical alterations. Symptomatology can be different, from subclinical to severe, focal or systemic disease. The causal agent comes from maternal flora or can be of community/hospital origin. Material and method: Our retrospective study evaluated 121 newborns (both preterm and term), divided into three groups: early onset sepsis (35), late onset sepsis (39), and control group (47), from 0 to 28 days old. Blood samples and cultures were collected at admission, after 24 hours, and 72 hours. Results: The two-sample Wilcoxon signed rank test revealed a statistically significant difference between the initial and final measures of lactate dehydrogenase (LDH) and ferritin within the early onset sepsis (EOS) and late onset sepsis (LOS) groups. No significant differences were observed for those two variables within the control group. There were significant differences for first and last measurements of C-Reactive Protein (CRP) (p = 0.029), leukocyte count (p = 0.002), and platelets (TR) (p = 0.00001). Conclusions: Ferritin is a potential biomarker that can be associated with systemic response and sepsis in both cases of early and late onset sepsis.

Keywords: Barriers; Facilitators; Sepsis; Sepsis Six Guidelines; Nurses.

This prospective single-center study was designed to assess the clinical utility of the FilmArray® blood culture identification (BCID) panel for improving the diagnostic accuracy in neonatal sepsis. Results obtained using the FilmArray® BCID panel were correlated with results of blood culture in all consecutive neonates with suspicion of early-onset (EOS) and late-onset sepsis (LOS) attended in our service over a 2-year period. A total of 102 blood cultures from 92 neonates were included, 69 (67.5%) in cases of EOS and 33 (32.3%) in LOS. The FilmArray® BCID panel was performed in negative culture bottles at a median of 10 hours of blood culture incubation (range 7.5-20 hours), without differences by the type of sepsis. The FilmArray® BCID panel showed a 66.7% sensitivity, 100% specificity, 100% positive predictive value, and 95.7% negative predictive value. There were four false-negative cases, three of which of Streptococcus epidermidis in neonates with LOS and one case of Granulicatella adiacens in one neonate with EOS. We conclude that the use of the FilmArray® BCID panel in negative blood cultures from neonates with clinical suspicion of sepsis is useful in decision-making of starting or early withdrawal of empirical antimicrobials because of the high specificity and negative predictive values of this assay.

Sepsis is a serious disease that can lead to mortality. The etiology of the disease is connected to how the body as a host reacts toward microbes such as bacteria, viruses, and fungi invasion. Current research shows that during sepsis, the reaction toward microbe attacks takes two main phases. The first is known as a cytokine storm, while the second is a vicious cycle of pro-inflammatory responses followed by a strict anti-inflammatory response led by CD4+ Tregs. Various immunomodulatory therapies have been proposed to break the cycle of pro- and anti-inflammatory reactions to sepsis. However, clinical trials did not show promising results, indicating further research into the mechanism that Treg uses to inhibit proinflammatory reactions. We used next-generation sequencing (NGS) analysis of bulk RNA-seq and single-cell RNA-seq data to examine the exact molecular pathways used by Treg to inhibit the immune response in sepsis. Our approach identified ACOD1 (Aconitate Decarboxylase 1) as a primary mediator of Treg suppression of immune cells. We identified and validated CD36 as a downstream target of ACOD1. CD36 is a known metabolite regulator in Tregs. Taken together, our results indicate that targeting ACOD1 could prove valuable in regulating Treg function during sepsis.

Severe COVID-19 disease is characterised by an exaggerated inflammatory response, called cytokine storm, accompanied by a condition of immune depression. Even sepsis is characterised by an exaggerated inflammatory response, called SIRS (Systemic Inflammatory Response Syndrome), accompanied by a condition of immune depression called CARS (compensatory anti-inflammatory response syndrome). Clinical studies reveal that most sepsis patients who did not die during the hyper inflammatory response (SIRS) subsequently succumbed to the condition of immune depression (CARS). Severe acute pancreatitis begins with local inflammation that induces systemic inflammatory response syndrome (SIRS), accompanied and followed by a compensatory anti-inflammatory response (CARS). In COVID-19 disease, the male response to SARS CoV-2 virus is typically characterised by a robust inflammatory response. Instead, a cell-mediated immune response is dominant in women. This means that the male sex tends to have a more robust hyper inflammatory response than the female one. Furthermore, in women the condition of immune depression is less represented, therefore they are more protected. Sepsis, severe acute pancreatitis and COVID-19 disease evolve between two fundamental aspects: hyper inflammation and immunodepression. The experience gained over years of studies of sepsis and severe acute pancreatitis suggests that therapies should be differentiated according to the evolutionary stage of the disease. The goal is to save the lives of most patients with COVID-19 disease. The identification of critical points, suitable for designing the windows of therapeutic opportunity, may allow the use of therapeutic interventions, in the COVID-19 disease, which are effective (there are no approved drugs yet), safe (without significant side effects), targeted (based on the evolutionary phase of the disease) personalized, (based on sex, co-morbidities, age, etc.) and timely (based on signs, symptoms, laboratory parameters and instrumental investigations).

Early onset neonatal sepsis is a significant contributor to neonatal morbidity and mortality. Although blood cultures remain the diagnostic gold standard, they detect pathogens in only a minority of suspected cases. This study compared the accuracy of blood cultures with a rapid multiplex PCR test. Newborns at risk for neonatal sepsis were prospectively screened as recommended per national guidelines. Evaluations included laboratory parameters (CrP, IL6, differential blood count), blood culture, and a molecular multiplex PCR test (ROCHE LightCycler SeptiFast) identifying 20 common microbial agents. Blood samples were taken simultaneously from umbilical cord or venous sources on the first day of life. Of 229 infants included, 69% were born preterm. Blood culture and multiplex PCR sensitivity were 7.4% and 11.1% respectively. Specificity, negative and positive predictive values between methods showed no significant variance, though multiplex PCR had more false positives due to contamination. The limited sensitivity of blood cultures for early onset neonatal sepsis is concerning. Despite quicker results, multiplex PCR does not enhance diagnostic accuracy or antibiotic therapy guidance, thus it can not be recommended for this indication.

Introduction: The objective of this study was: compare the continuous infusion of cefepime with the intermittent infusion in patients with sepsis caused by Gram negative bacilli (GNB). Methods: Randomized 1:1 multicenter double-blinded placebo-controlled study with allocation concealment. Multicenter study in Intensive Care Units of Colombia. Patients with sepsis, severe sepsis or septic shock and GNB suspected bacteraemia. Cefepime was administered for 7 to 14 days over 30 m intermittently every 8 h over 24 h plus continuous saline solution (0.9%) (G1) or 3 g administered continuously plus saline solution every 8 h (0.9%) (G2). Percentage of clinical response at 3, 7, 14 days, relapse at 28 days and mortality at discharge were measured. Results: The recruitment was stopped by suggestion of the Institutional Review Board (IRB), following an FDA alert about cefepime. Thirty-two patients were randomized, 25 received the intervention and GNB bacteremia was confirmed in 16 (9 G1 and 7 G 2). Favourable clinical response in days 3,7,14 was 88.8%, 88.8%, 77.8 % (G 1) and was similar for G 2 (85.7%). There were not relapses and deaths in G2 while in G1 one relapse and 2 deaths were observed. Conclusions: The results of this study support the use of cefepime for the treatment of Gram-negative infections in critically ill patients but we could not demonstrate differences between continuous or intermittent administration, because of the small sample size, given the early suspension of the study.

Background: Sepsis still represents a major public health issue worldwide, and immune system plays a main role during infections and therefore its activity is mandatory to resolve this clinical condition In this report we aimed to retrospectively verify in real life setting the possible usefulness of Pentameric IgM plus antibiotic in recovering patients with sepsis after major abdominal surgery Materials/methods: We reviewed, from January 2013 until December 2018, all adult patients admitted in ICU for Sepsis or Septic shock (2) after major abdominal surgery. Among these patients, were identified those that according to legal indication and licence in Italy, were treated with Pentameric IgM plus antibiotic (Group A) or with antibiotic alone (Group B). We analysed the following parameters were evaluated: Blood gas analysis, Lactate, CRP, Procalcitonin, Endotoxin activity, Liver and Renal Function, Coagulation, Blood Cell count at different time points (Every 48 hrs for at least 7 days. Differences between groups have been analysed by Fisher’s exact test or Chi square test for categorical variables. Mann–Whitney U test or Kruskal–Wallis test have instead been performed to compare continuous variables. Univariate and Multivariate analysis were also performed Results: Over a period of 30 months 24 patients were enrolled in Group A and 20 patients in Group B. In those subjects no statistical differences have been found in terms of bacterial or fungal infection isolates, when detected in a blood culture test, or in inflammatory index, SOFA score, lactate levels and mortality rate. A 48hrs response was statistically more frequent in Group B than in Group A, while no differences were found in the other clinical and laboratory evaluation. Conclusions: Based on our results, the use of pentameric IgM do not seem to give any clinical advantage in sepsis after to major abdominal surgery.

Sepsis, a syndrome characterized by systemic inflammation during infection, continues to be one of the most common causes of patient mortality in hospitals across the United States. While standardized treatment protocols have been implemented, wide variability in clinical outcomes persist across racial groups. Specifically, Black and Hispanic populations are frequently associated with higher rates of morbidity and mortality in sepsis compared to the Caucasian population. While this is often attributed to systemic bias against minority groups, a growing body of literature has found patient, community, and hospital-based factors to be driving racial differences. In this article, we provide a focused review on some of the factors driving racial disparities in sepsis. We also suggest potential interventions aimed at reducing health disparities in the prevention, early identification, and clinical management of sepsis.

Background: Recent reports on the national temporal trends of sepsis-related mortality in the United States (US) suggested outcome improvement in several race and ethnicity groups. However, it is unknown whether national data reflect state-level trajectories. Methods: We used the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death dataset to identify all decedents with sepsis in the US during 2010-2019. Negative binomial regression models were fit to estimate national and state-level trends of age-adjusted sepsis-related mortality rates within race and ethnicity groups. Results: There were 1,852,610 sepsis-related deaths in the US during 2010-2019. Nationally, sepsis-related mortality rates decreased among Blacks and Asians, were unchanged among Hispanics and Native Americans, and rose among Whites. The percent of states with similar trends were 30.0% among Blacks, 32.1% among Asians, 74.3% among Hispanics, 75.0% among Native Americans, and 66.7%% among Whites, while trending in opposite direction from 3.6% among Asians to 15.0% among Blacks. Conclusions: National trends in sepsis-related mortality in the US did not represent state-level trajectories in race and ethnicity groups. Gains in sepsis outcomes among race and ethnicity groups at the national level were not shared equitably at the state level.

Sepsis is an inflammatory disorder caused by the host’s dysfunctional response to infection. Septic patients present diverse clinical characteristics, and in the recent years it has been the main cause of death in intensive care units (ICU). Aquaporins, membrane proteins with role in water transportation, have been reported to participate in numerous biological processes. Their role in sepsis progression has been studied extensively. This review aims to examine recent literature on aquaporin expression and regulation in clinical sepsis, as well as established experimental models of sepsis. We will present how sepsis affects aquaporin expression at the molecular and protein level. Moreover, we will delve into the importance of aquaporin regulation at the transcriptional, post-transcriptional, translational, and post-translational level in sepsis, by presenting data on aquaporin regulation by non-coding RNAs and selected chemical molecules. Finally, we will focus on the importance of aquaporin single nucleotide polymorphisms in the setting of sepsis.

The aim of this study was to determine the potential of early inflammatory markers to diagnose late-onset neonatal sepsis - procalcitonin (PCT), interleukin 6 (IL-6), interleukin 8 (IL-8) and endocan (ESM-1), and to compare them with routinely used markers. A prospective (January, 2022 – January, 2023) clinical-epidemiological study was conducted in a third level NICU in Pleven, Bulgaria. Patients with suspected nosocomial infection and healthy controls were tested. A sandwich ELISA method was used to measure the serum concentrations. Sixty newborns with an average gestational age of 29.75 ± 3.61 gestational weeks were included, of which 35 % were symptomatic and infected, 33.3 % were symptomatic but uninfected, and 31.7 % were asymptomatic controls. The mean values of PCT, IL-6, I:T index and PLT differ significantly in the three groups. For ESM-1, IL-8 and CRP, the difference was statistically insignificant. The best sensitivity (78%) and negative predictive value (84%) was found for IL-6. The combination of PCT + IL-6 + I:T+ PLT demonstrated high precision (78%) and best sensitivity (94%) and negative predictive value (95%). The introduction into routine practice of indicators such as PCT and IL-6 may provide an opportunity to promptly optimize the diagnostic and therapeutic approach to LOS.

Background： Sepsis-induced acute lung injury (ALI) is characterized by disruption of the epithelial barrier and activation of alveolar macrophages (AMs), which leads to uncontrolled pulmonary inflammation. However, effective treatments for ALI are unavailable. This study aimed to discover potential diagnostic molecular biomarkers based on bioinformatics, which will benefit the diagnosis and treatment of sepsis-induced ALI. Methods: GSE10474 was analyzed for differentially expressed genes (DEGs) in sepsis patients with ALI (sepsis + ALI) compared with sepsis patients without ALI. Functional enrichment analysis and protein-protein interaction (PPI) network were performed. on the DEGs via R package “clusterProfiler”, and visualized via Cytoscape. Prediction analysis of microarrays (PAM) was performed to identify diagnostic biomarkers and the diagnostic ability of diagnostic biomarkers was accessed via receiver operating characteristic (ROC) curves. Moreover, interactions among diagnostic biomarkers were analyzed via GeneMANIA. We also analyzed the function of diagnostic biomarkers and predicted their corresponding drugs via Cytoscape plugin BiNGO and web tool DGIdb. At last, we analyzed the transcriptional regulation of the diagnostic biomarkers via the web tool miRNet. Results: 71 genes were found to be differentially expressed in the sepsis + ALI group, mainly involved in immune-related biological processes and pathways. STRING database indicated 31 DEGs have protein-protein interactions. In addition, the PAM identified 6 diagnostic biomarkers, including HIST1H4H, CDKN1A, HMOX1, NQO2, RHOB, and TREM1, from these 31 DEGs. Conclusion: In conclusion, through bioinformatics analyses, we identified 6 potential diagnostic biomarkers and targets for sepsis-induced ALI.

Patients with end stage liver disease (ESLD) undergoing liver transplantation are prone to thromboses both while on the waiting list or in the perioperative period. This hypercoagulability is associated with significant endothelial dysfunction (ED) due to nitric oxide dysregulation. ED in combination with increased thrombin generation are the main factors responsible for this hypercoagulability. Sepsis itself can significantly change the coagulation profile, but in combination with ESLD, sepsis, and septic shock is responsible for very complex changes in the patients coagulation making both assessment and management of coagulation in patients with ESLD very challenging. Viscoelastic testing (VET) is a preferred method of coagulation management in patients with cirrhosis because, as with standard laboratory testing, VET can assess the entire coagulation system including the interaction between both pro- and anticoagulants and platelets.

The unknown timing of appropriate initiation of administration has led to controversy over the use of hydrocortisone in the treatment of neonatal sepsis. This study sought to compare the survival rate and NF-κB pathway expression level in newborn mice treated with hydrocortisone at different initiation times after sepsis to find the appropriate administration time window for clinical neonatal sepsis patients. Before building the sepsis model, 36 newborn C57BL/6 mice were randomly divided into six groups with six mice, using quasi-randomization: five treatment subgroups(1 h, 6 h, 12 h, 24 h and 48 h based on the initiation of hydrocortisone therapy) and 1 control group. The survival rate of mice in each group was compared. The expression levels of the NF-κB pathway and inflammatory factors were analyzed and compared among groups. Initiation of hydrocortisone therapy within 12 h of sepsis onset improved the survival of LPS-induced newborn septic mice. Treatment with hydrocortisone over 12 hours reduced the expression level of NF-κB and lowered serum IL-6 and TNF-α levels in cardiopulmonary tissues of mice. Administration of hydrocortisone early in sepsis (within 12 hours) promotes neonatal mouse survival by inhibiting the NF-κB pathway.

Antimicrobial peptides (AMPs) have emerged as a promising class of bioactive molecules with the potential to combat infections associated with medical implants and biomaterials. This review article aims to provide a comprehensive analysis of the role of antimicrobial peptides in medical implants and biomaterials, along with their diverse clinical applications. The incorporation of AMPs into various medical implants and biomaterials has shown immense potential in mitigating biofilm formation and preventing implant-related infections. We review the latest advancements in biomedical sciences and discuss the AMPs that were immobilized successfully to enhance their efficacy and stability within the implant environment. We also highlight successful examples of AMP coatings for the treatment of surgical site infections (SSIs), Contact lenses, Dental Applications, AMP-Incorporated Bone Grafts, Urinary tract infections (UTIs), Medical Implants, etc. Additionally, we discuss the potential challenges and prospects of AMPs in medical implants, such as effectiveness, instability and implant-related complications. We also discuss strategies that can be employed to overcome the limitations of AMP-coated biomaterials for prolonged longevity in clinical settings.

Background: Ceftobiprole is a fifth-generation cephalosporin that has been approved in Europe solely for the treatment of community-acquired and nosocomial pneumonia. The objective was to analyze the use of ceftobiprole medocaril (Cefto-M) in Spanish clinical practice in patients with infection in hospital or outpatient parenteral antimicrobial therapy (OPAT). Methods: This retrospective, observational, multicenter study included patients treated from September 1, 2021 to December 31, 2022. Results: 249 individuals were enrolled, aged 66.6±15.4 years, 59.4% male, with Charlson index of 4 (IQR 2-6); 13.7% had COVID-19, and 4.8% were in intensive care unit (ICU). The most frequent type of infection was respiratory (55.8%), followed by skin and soft tissue infection (21.7%). Cefto-M was administered to 67.9% as empirical treatment, being in monotherapy for 7 days (5-10) in 53.8% of cases. The infection-related mortality was 11.2%.The highest mortality rates were for ventilator-associated pneumonia [40%], and infections due to methicillin-resistant S. aureus (20.8%) and Pseudomonas aeruginosa (16.1%). Mortality-related factors were age (OR: 1.1, 95%CI [1.04-1.16]), ICU admission (OR:42.02, 95%CI[4.49-393.4]), and sepsis/septic shock (OR:2.94, 95%CI [1.01-8.54]).Conclusions: In real life, Cefto-M is a safe antibiotic, with only half of prescriptions in respiratory infections, mainly administered as rescue therapy in pluripathological patients with severe infectious diseases.

Is HSP-27 an emerging marker of good prognosis in septic shock patients – a pilot study Objective To estimate the value of serum changes of C-reactive protein, procalcitonin, presepsin, heat shock protein 27 (HSP27) and neutrophil to lymphocyte ratio in assessing the prognosis in patients with septic shock (SS) treated in intensive care unit. Methods The SS was diagnosed and treated in accordance with the guidelines of the Surviving Sepsis Campaign. 37 selected adult patients with SS were included. Serum concentrations of biomarkers were measured at admission and daily for 4 consecutive days (time points T0,T1, T2, T3 and T4 respectively). The mortality rate was determined 28 days after admission. Patients were divided into survivor and non-survivor groups according to their mortality. The differences between the levels of biomarkers at the T0 and T4 time points were analyzed. Results The mean value of the SOFA score on admission was 11.7 ± 2.7, and the APACHE II scale 29.9 ± 6.85. Nine patients died. Univariate logistic analysis revealed that changes between T0 and T4 time points of presepsin, procalcytonin, and HSP27 were associated with prognosis. A multivariate Cox analysis showed that an increase in HSP27 on T4 was the only independent predictor of good prognosis in SS patients. The area under the receiver operating characteristics curve for HSP27 was 0.785. Kaplan–Meier analysis showed that the mortality was lower (p=0.014) in patients who had an increase in HSP27 on T4 compared to those whose serum HSP27 did not increase on T4. Conclusions The increase of HSP27 level on the 4th day predicts favorable outcome in SS patients.

Sepsis is a life-threatening condition caused by a dysregulated host response to an invading pathogen such as multidrug-resistant bacteria. Despite recent advancements, sepsis is a leading cause of morbidity and mortality, resulting in a significant global impact and burden. This condition affects all age groups, with clinical outcomes depending mainly on timely diagnosis and appropriate early therapeutic intervention. Because of the unique features of nanosized systems, there is a growing interest in developing and designing novel solutions. Nanoscale-engineered materials allow a targeted and controlled release of bioactive agents, resulting in improved efficacy with minimal side effects. Additionally, nanoparticle-based sensors provide a quicker and more reliable alternative to conventional diagnostic methods for identifying infection and organ dysfunction. Despite recent advancements, fundamental nanotechnology principles are often presented in technical formats that presuppose advanced chemistry, physics, and engineering knowledge. Consequently, clinicians may not grasp the underlying science, hindering interdisciplinary collaborations and successful translation from bench to bedside. In this review, we abridge some of the most recent and most promising nanotechnology-based solutions for sepsis diagnosis and management using an intelligible format to stimulate a seamless collaboration between engineers, scientists, and clinicians.

Based on Chinese CDCP report on COVID-19, 14% of patients presented severe disease and 5% critical conditions. The average case-fatality rate was 2.3%, but mortality was as high as 49% in patients with critical illness. Serious life threatening thromboembolic complications have been found in 71·4% of non-survivors and micro/macro angiopathic coagulopathy has been found, also at autopsy, with highly increased neutrophil number, fibrinogen, concentrations of D-dimer and FDPs and NETs, ATIII decrease and normal number of platelets. A cytokine storm and interaction between inflammation and coagulation has been advocated as explanation of hypercoagulability. In this paper, it’s hypothesised that SARS-CoV-2 infection of alveolar cells induces recruitment of innate responder neutrophils, which release proteases and NETs inducing endothelial damage/endotheliopathy and imbalance of the four major proteolytic cascades (coagulation, complement, fibrinolysis and kallikrein) with prevalence of activators over inhibitors and consequent thrombotic complications. Platelets adhesion to damaged endothelium and the presence of ULVWF multimers, due to decreased ADAMTS13, contributes to the state of hypercoagulability. Neutrophil innate “unfriendly fire” response can be identified as the trigger of a “proteolytic storm”, responsible for subsequent well known prothrombotic condition and “cytokine storm”. The hypothesis explains also the pathology of recently described systemic “Kawasaki Disease like” vasculitis cases in Covid-19 young ill patients.

Background: Little is known about risk and prognostic factors in very old patients developing sepsis secondary to community-acquired pneumonia (CAP). Methods: We conducted a retrospective observational study of data prospectively collected at the Hospital Clinic of Barcelona over a 13-year period. Consecutive patients hospitalized with CAP were included if they were very old (≥80 years) and divided into those with and without sepsis for comparison. Sepsis was diagnosed based on the Sepsis-3 criteria. The main clinical outcome was 30-day mortality. Results: Among the 4,219 patients hospitalized with CAP during the study period, 1,238 (29%) were very old. The prevalence of sepsis in this aged group was 71%. Male sex, chronic renal disease, and diabetes mellitus were independent risk factors for sepsis, while antibiotic therapy before admission was independently associated with a lower risk of sepsis. Thirty-day and intensive care unit (ICU) mortality did not differ between patients with and without sepsis. In CAP-sepsis group, chronic renal disease and neurological disease were independent risk factors for 30-day mortality. Conclusion: In very old patients hospitalized with CAP, in-hospital and 1-year mortality rates were increased if they developed sepsis. Antibiotic therapy before hospital admission was associated with a lower risk of sepsis.

Successful implementation of antibiotic stewardship programs (ASP) requires a well-structured approach involving all stakeholders. Despite embracing key responsibilities, nurses’ role remains poorly defined, preventing consistent engagement. We conducted a scoping survey to assess knowledge, attitude and perception of nurses towards nurse-led initial sepsis risk evaluation using the sepsis risk calculator (SRC) of newborns admitted to the mother-baby unit. Single-center, cross-sectional study. Study link was sent to all full-time nurses in mother-baby unit. Survey centered around knowledge of unit’s ASP and attitude and perception towards nurse-led initial sepsis risk evaluation. 89% response rate. 100% agreed that SRC reduced antibiotic use and 66% felt nurse-led sepsis risk evaluation will enhance nurse involvement, but this was offset by extra burden of work (66%) and low confidence in differentiating stable from clinically unstable infants (46%). Other facilitating factors included greater nurse/patient ratio (100%), targeted education (89%) and incorporation of the SRC into EMR (78%). Only 11% were willing to serve as champions for it. There was no significant correlation to age or experience however, greater number of fresh grads were interested in championing this effort. Our study identifies a need for strong foundation of knowledge and greater nurse/patient ratio as two main factors for improving nurse-led use of the SRC. Multi-site studies scoping barriers to nursing involvement for successful implementation of ASPs are necessary.

Exercise induced bronchoconstriction (EIB) is a common complication of athletes and individuals who exercise regularly. It is estimated that about 90% of patients with underlying asthma experience EIB. Sex differences in the prevalence of asthma have been widely reported, with higher rates in boys vs. girls before puberty, and higher rates in women than men after puberty. Because atopy has been reported to occur at higher rates in athletes than in non-athletes, in this study we investigated sex differences in EIB and atopy in athletes. A systematic literature review identified 60 studies evaluating EIB and/or atopy in post-pubertal adult athletes (n=7501). Collectively, these studies reported: 1) a 23% prevalence of EIB in athletes; 2) a higher prevalence of atopy in male athletes vs. females; 3) a higher prevalence of atopy in athletes with EIB; and 4) a significantly higher rate of atopic EIB in male vs. female athletes. Our analysis indicates that the physiological changes that occur during exercise may differentially affect male and female athletes, and suggest an interaction between male sex, exercise, and atopic status in the course of EIB. Understanding these sex differences is important to provide personalized management plans to athletes with underlying asthma and/or atopy.

Neonatal sepsis is a leading cause of morbidity and mortality in neonates, particularly in low and middle-income countries. The emergence of antimicrobial resistance is a rapidly growing global problem. A significant proportion of the pathogens that commonly cause neonatal sepsis are resistant to multiple antibiotics. Therefore, for the empirical treatment of neonatal sepsis, the repurposing of older antibiotics that are effective against multidrug-resistant pathogens is being investigated. This review aims to provide an overview of current research and experience using the repurposed antibiotics, Colistin and Fosfomycin, for the empirical treatment of neonatal sepsis. Based on current knowledge, Colistin and Fosfomycin may be potentially helpful for the empirical treatment of sepsis in neonates due to their efficacy against a wide range of pathogens and acceptable safety profile.

Abstract Background Pentraxin 3 (PTX3), an acute-phase protein associated with innate immunity, serves as a promising biomarker with diagnostic and prognostic value in preterm newborns. We aimed to investigate the relationship between PTX3 levels in neonates diagnosed with FIRS and early postnatal outcomes. Material and methods The study was designed as a prospective study. A total of 62 infants, 28–36 weeks of gestational age, were enrolled. During their neonatal intensive care unit (NICU) stay, the patients' mortality and morbidity outcomes were recorded and monitored. PTX3 concentrations were studied in plasma in the maternal peripheral blood and umbilical/peripheral veins of neonates. The relationship between PTX3 concentrations and neonatal outcomes was investigated using non-parametric tests, regression analysis, and receiver operating characteristic (ROC) analysis. Results PTX3 levels in cord blood and peripheral blood samples of neonates were significantly associated with clinical conditions such as respiratory distress syndrome (RDS) (p = 0.022), sepsis (p = 0.001), neonatal pneumonia (p = 0.016), and FIRS (p = 0.001). In infants with FIRS, the increase in PTX3 was statistically significant (p = 0.013), with an OR of 1.131 (95% CI 1.026–1.246). The PTX3 level had a cutoff value >4.45 (p<0.001) for predicting FIRS with an AUC of 0.759, 76.9% sensitivity (95% CI 56.4–91), and 63.9% specificity (95% CI 46.2–79.2). Conclusions This study demonstrates that PTX3 shows potential as a sensitive and specific biomarker for the early diagnosis of FIRS in preterm newborns. PTX3 levels were significantly associated with clinical outcomes such as RDS, sepsis, neonatal pneumonia, and FIRS.

HMGB1 is a key late inflammatory mediator upregulated during air pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays significant roles in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 level may restore innate immune cell functions to protect the lungs from harmful injuries. Current therapies for air-pollution induced respiratory problems are inadequate. Dietary antioxidants from natural sources could serve as a frontline defense for air pollution-induced oxidative stress lung damage. Here, a standardized bioflavonoid antioxidant composition from Scutellaria baicalensis and Acacia catechu was evaluated for its efficacy in attenuating acute inflammatory lung injury and sepsis induced by oxidative stress and endotoxemia. Murine hyperoxia-exposed, bacterial-challenged acute lung injury, LPS-induced sepsis, and LPS-induced acute inflammatory lung injury models were utilized in vivo. Effect of the bioflavonoid composition on phagocytic activity and HMGB1 release was assessed using hyperoxia-stressed macrophages in vitro. Hematoxylin-eosin (HE) staining for lung tissue damage evaluation, ELISA for inflammatory cytokines and chemokines, western blot analysis for protein and HMGB1 as well as bacterial counts in the lung and airways have been performed. Statistically significant decrease in mortality (50%), reduced proinflammatory cytokines (TNF-α, IL-1β, IL-6) and chemokines (CINC-3) in serum and bronchoalveolar lavage, increased bacterial clearance of airways and lungs; reduced airway total protein, and extracellular HMGB1 were observed in vivo. A statistically significant 75.9% reduction in the level of HMGB1 and increased phagocytosis activity were also observed in vitro. The compilation of data in this report strongly suggest that the bioflavonoid composition could be indicated for oxidative stress induced lung damage protection possibly through attenuation of extracellular HMGB1.

Cryptococcosis is a leading cause of death among people with HIV in sub-Saharan Africa. Limited diagnostic and therapeutic options significantly impair treatment options in Africa. We investigated the burden of cryptococcosis and related mortality among people with HIV and suspected sepsis in Ethiopia. We conducted a prospective cohort at 1) Adama Hospital Medical College and 2) Asella Referral and Teaching Hospital from September 2019 to November 2020. We enrolled adult HIV-infected patients presenting with suspected sepsis and assessed 28-day survival. We performed blood cultures and cryptococcal antigen (CrAg) testing. In total, 82 participants were enrolled with a median age of 35 years and 61% being female. Overall, 11(13%) had positive CrAg tests, of which 5 had Cryptococcus detected in blood cultures. Despite high-dose fluconazole (1200mg/d) monotherapy in patients with positive CrAg tests, the 28-day mortality was 64%(7/11), being significantly higher than in CrAg-negative patients (9%(6/71); p&lt;0.001). Cryptococcosis is the leading cause of mortality among HIV-infected sepsis patients. CrAg screening in HIV-infected patients attending emergency department can minimize the cryptococcosis missing case irrespective of CD4 count and viral load. These findings warrant the need of a bundle approach for diagnosis of HIV-infected persons presenting with sepsis in low- and middle-income countries.

Sepsis is associated with dysregulated cortisol secretion, leading to abnormal levels of cortisol in the blood. In the early stages of sepsis, cortisol levels are typically elevated due to increased secretion from the adrenal glands. However, as the disease progresses, cortisol levels may decline due to impaired adrenal function, leading to relative adrenal insufficiency. The latter is thought to be caused by a combination of factors, including impaired adrenal function, decreased production of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) by the hypothalamus and pituitary gland, and increased breakdown of cortisol by enzymes such as 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). The dysregulation of cortisol secretion in sepsis is thought to contribute to the pathophysiology of the disease by impairing the body's ability to mount an appropriate inflammatory response. The actions of cortisol are mediated through two types of corticosteroid receptors: the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GCR). In sepsis, the expression and activity of GCR is altered, contributing to the pathophysiology of the disease. GCR expression and activity are typically downregulated in sepsis, impairing the body's ability to mount an appropriate inflammatory response. Given the dysregulation of cortisol secretion and corticosteroid receptors in sepsis, there has been considerable interest in the use of steroids as a treatment for sepsis. The rationale for steroid-based treatment is to supplement the body's endogenous cortisol production, restore normal cortisol levels, and improve the body's ability to mount an appropriate inflammatory response. However, the use of steroids in sepsis remains controversial, and clinical trials have yielded mixed results. Some studies have shown that steroid-based treatment can improve shock reversal, reduce the need for vasopressors, and improve overall survival in patients with septic shock, whereas other studies have found no benefit or even harm from steroid-based treatment in sepsis.

Sepsis is a life-threatening condition with high hospital mortality. Elevated mortality has also been observed in patients after hospital discharge due to post-sepsis syndrome (PSS). The etiology of PSS is still not entirely known, but it involves inflammation. Plasma extracellular vesicles (EVs) are recognized as a unique mechanism of intercellular communication in inflammatory processes. It has been reported that EV microRNA (miRNA) production during the acute sepsis phase may persist until after disease resolution and is associated with PSS. We employed mass spectrometry and qPCR analysis to determine the protein and miRNA composition of plasma-derived EVs of 36 patients during sepsis-related hospitalization, immediately after ICU discharge (post-sepsis), and three, six, twelve, and up to 36 months post-sepsis. We determined that patients’ immune system cells were the primary EV source. Fifteen differentially expressed EV miRNAs (DEmiRs) were identified in samples from septic patients compared to the control group. Predictive analyses revealed that these DEmiRs could influence inflammation by modulating pathways mediated by NF-κB, STAT3, and TLR4 signaling activation. Thirteen miRNAs (-15b-5p,-16-5p,-20a-5p,-25-3p,-27a-3p,-29a-3p,-30d-5p,-93-5p,-146a-5p,-148a-3p,-191-5p,-195-5p,-223-3p) were downregulated in the death group compared to the survivor group, making them candidate prognostic markers of ICU survival. One year after ICU discharge, the expression of miR-21-5p and miR-195-5p were decreased in the survivor group. The miRNAs identified in the present study represent potential biomarkers for the survival prognosis of post-sepsis patients.

Current interventions are not effectives in preventing sepsis-induced acute kidney injury and its long-term outcomes or even after second renal insult. Therapeutic strategies using lipid mediators, as aspirin-triggered resolvin D1 (ATRvD1), can contribute for resolution of acute and chronic inflammation. In this study, we examined the potential effect of ATRvD1 on long-term kidney dysfunction after severe sepsis. Fifteen days after cecal ligation and puncture (CLP), sepsis-surviving BALB/c mice were subjected to a tubulointerstitial injury through intraperitoneal injections of bovine serum albumin (BSA) for 7 days, called subclinical acute kidney injury (subAKI) animal model. ATRvD1 treatment was performed right before BSA injections. On day 22 after CLP, urinary protein/creatinine ratio (UPC), histologic parameters, fibrosis, cellular infiltration, apoptosis, inflammatory markers levels, and mRNA expression were determined. ATRvD1 treatment mitigated tubulointerstitial injury by reducing the proteinuria excretion, UPC ratio, glomerular cell number and extracellular matrix deposition. Pro-fibrotic markers, as transforming growth factor β (TGFb), type 3 collagen and metalloproteinase (MMP)-3 and -9 were reduced after ATRvD1 administration. Post-septic mice treated with ATRvD1 were protected from renal apoptosis and recruitment of F4/80+ cells. Interleukin-1b (IL-1b) levels were increased in subAKI animal model, being attenuated by ATRvD1. Tumor necrosis factor-a (TNF-a), IL-10 and IL-4 mRNA expression was increased in the kidney of BSA-challenged post-septic mice and it was also reduced after ATRvD1. These results suggest that ATRvD1 protects the kidney against a second insult as BSA-induced tubulointerstitial injury and fibrosis by suppressing inflammatory and pro-fibrotic mediators in renal dysfunction after sepsis.

Objectives: To investigate the value of early lactate dynamic monitoring index in predicting prognosis of patients with sepsis and septic shock. Methods: We performed our test on 50 patients. Out of 50 patients, 28 are male, and 22 are female. Prospectively studied pediatric patients with septic shock were performed. Vital signs, Lactate clearance, were obtained at presentation 6 h, 12 h, 24 h over the first 48 h of hospitalization. The therapy received, outcome parameters of mortality and duration of hospitalization were recorded. Results: The statistical data and comparative analysis showed that an average of 16.88 days after admission, 5 patients have died, 17 patients are poorly prognosis leaves the hospital, and the remaining 28 are recovered and discharged. The primary outcome variable of mean 16 days hospitalization mortality rate was 10%. Poor prognosis 34% and fully recovery 56 % were observed. In this retrospective cohort study, a lactate level of more than 2.5mmol/L was the best threshold to predict 28-day mortality among severe sepsis and septic shock patients. In our research, we found mean LC 6 h 3.08mmol/L, and after 48 h mean it is 1.79mmol/L. Significant LC 6 h found, which is 8.08mmol/L in the death group patient where 48 h mmol/L shows significant high. Poor prognosis also presents a clinical increase of lactate level high in the LC 6 h analysis, which is 3.32mmol/L. Recovered patients showed a significant improvement after administering treatment depending on the patient organ involvement and good decrease of lactate reports achieved, which is 1.20mmol/L, where admission reports show it was 1.91mmol/L in LC 6 h. Mean Heart rate 94/51mmhg, pulse 119, temperature 39℃, respiratory rate 32.26, and urine output 456 ml recorded during our study. Death patient shows a remarkable detonation of those reports but has a significant clinical report with the recovered patients. Conclusion: The early lactate dynamic monitoring index has a high value in predicting sepsis and septic shock patients' prognosis, thus worth popularizing.

Critically ill patients with sepsis require a multidisciplinary approach, as this situation implies multiorgan distress, with most of the bodily biochemical and cellular systems being affected by the condition. Moreover, sepsis is characterized by a multitude of biochemical interactions and by dynamic changes of the immune system. At the moment, there is a gap in our understanding of the cellular, genetic, and molecular mechanisms involved in sepsis. One of the systems intensely studied in recent years is the endocannabinoid signaling pathway, as light was shed over a series of important interactions of cannabinoid receptors with biochemical pathways, specifically for sepsis. Furthermore, a series of important implications on inflammation and the immune system that are induced by the activity of cannabinoid receptors stimulated by the delta-9-tetrahidrocannabinol and cannabinol have been noticed. The aim of this review paper was to present, in detail, the important mechanisms modulated by the endocannabinoid signaling pathway, as well as of the molecular and cellular links it has with sepsis. At the same time, we wish to present the possible implications of cannabinoids in the most important biological pathways involved in sepsis, such as inflammation, redox activity, immune system, and epigenetic expression.

Background: Most sepsis patients died during their first episode and the long-term survival post discharge was low. Major adverse cardiovascular events and repeated infections were regarded as the major causes in such conditions. No definite medications were proven to effectively improve the long-term outcome. We aimed to examine the benefit of statins on the long-term outcome of survived sepsis patients. Methods: Between 1999 and 2013, a total of 220,082 patients with the first episode of sepsis hospitalization were included and 134,448 ones (61.09%) survived to discharge. The survived patients who subsequently had statins use of >30 cumulative defined daily doses (cDDDs) post discharge were defined as the statin users. After propensity score matching of 1:5, a total of 7,356 and 36,780 survived patients were retrieved as the study (statin-users) and comparison cohort (non-statin users), respectively. The main outcome was the long term survival post discharge. HR with 95% CI was calculated using the Cox regression model to evaluate the effectiveness of statins with further stratification analyses according to cDDDs. Results: The study cohort, that is, the statin users had an adjusted HR of 0.29 (95% CI, 0.27-0.31) in long term mortality rate compared with the comparison cohort. For statin users with the cDDDs of 30–180, 180–365, and >365, the adjusted HRs were 0.32, 0.22, and 0.16, respectively, (95% CI, 0.30-0.34, 0.19-0.26, and 0.12-0.23, respectively) compared with the non-statin users (defined as statins use <30 cDDDs post discharge), and the P for trend <.0001. In the sensitivity analysis, after excluding the survived patients who died within three and six months post discharge, the adjusted HR of statins use remained significant (0.35, 95% CI 0.32-0.37 and 0.42, 95% CI 0.39-0.45, respectively). Conclusions: Statins decreased the long-term mortality post sepsis. Further randomized control trial deserved to be conducted to confirm this observation.

For decades, sepsis research has been motivated by the idea of a dangerous overreaction of the immune system in sepsis. But is it true that the response to sepsis is dysregulated? This review surveys the history of sepsis trials and found that evidence for dysregulation does not exist in many of the physiologic mechanisms of sepsis. It is time to consider the alternative hypothesis, that sepsis traits are often functional, and do more harm than good. This review discusses the implications of this perspective for the future of sepsis research

Background Diabetic patients have an increased risk of infections; however, the association between type 2 diabetes and hospital outcomes of sepsis remains controversial when the diabetes severity is not considered. We examined this association using nationwide and hospital-based databases concomitantly. Methods The first part of this study was conducted using 2 nationwide databases: the Longitudinal Cohort of Diabetes Patients and the Longitudinal Health Insurance Database 2000. The diabetic complication burden was evaluated using the adapted Diabetes Complications Severity Index score (aDCSI score). In the second part, we used the hospital-based database with laboratory data, such as initial blood glucose and HbA1c levels, to make comparisons between surviving and dead patients with type 2 diabetes and sepsis. Results The nationwide study included 19,719 type 2 diabetic sepsis patients and an equal number of non-diabetic patients. The diabetic sepsis patients had an increased odds ratio (OR) of 1.14 (95% CI 1.1-1.19) for hospital mortality. The OR for mortality increased as the complication burden increased (diabetic sepsis patients with aDCSI scores of 0, 1, 2, 3, 4, and ≥5 had ORs of 0.91, 0.87, 1.14, 1.25, 1.56, and 1.77 for mortality, respectively (all P<0.001 and P for trend <0.001)). A total of 1,054 diabetic sepsis patients were included from the hospital-based database. Initial blood glucose levels in the surviving and dead diabetic sepsis patients did not differ significantly: 273.9 ± 180.3 versus 266.1 ± 200.2 (mg/dL) (P=0.095). Moreover, the surviving diabetic sepsis patients did not have a lower HbA1c (%): 8.4 ± 2.6 versus 8.0 ± 2.5 (P=0.078). Conclusions In the case of type 2 diabetic sepsis patients, the diabetes-related complication burden is the major determinant of hospital mortality rather than the diabetes itself. Contrary to popular belief, initial blood glucose and HbA1c levels may not be as important as previously thought.

Movement disorders can be associated with various drugs and systemic diseases, posing diagnostic challenges for clinicians. This review explores the spectrum of movement disorders associated with pharmacological agents and medical conditions. Drug-induced movement disorders encompass a broad range of conditions resulting from exposure to medications that affect several neurotransmitters. Neuroleptic medications can lead to tardive dyskinesia, characterized by involuntary, repetitive movements. Antipsychotics and antiemetics, including metoclopramide, may induce acute dystonic reactions. Other drugs, such as dopamine receptor-blocking agents, can contribute to drug-induced parkinsonism. Beyond medications, movement disorders can also arise secondary to systemic diseases. Metabolic disorders like Wilson's disease, characterized by copper accumulation, may manifest as chorea or dystonia. Inflammatory conditions such as rheumatoid arthritis and systemic lupus erythematosus can result in secondary movement disorders due to autoimmune-mediated processes affecting the central nervous system. Movement disorders linked to drugs or systemic diseases often necessitate a thorough clinical evaluation, including detailed medication histories and comprehensive systemic assessments. Neuroimaging, laboratory investigations, and, in some cases, cerebrospinal fluid analyses and electrodiagnostic studies help in establishing accurate diagnoses. Management involves addressing the underlying cause, modifying medications, and employing symptomatic treatments.

Background: Effective identification and management in the early stages of sepsis are critical for achieving positive outcomes. In this context, neutrophil activation status (NEUT-RI) emerges as a promising and easily interpretable parameter. This study aimed to assess the predictive value of NEUT-RI in diagnosing sepsis and to evaluate its prognostic significance in distinguishing 28-day mortality outcomes. Materials: The study is a secondary retrospective observational analysis. Clinical data upon ICU admission were collected. A control group of critically ill patients without sepsis criteria was included. Patients were divided into subgroups based on renal function for biomarker evaluation, with 28-day outcomes reported for septic and non-septic patients. Results: 200 patients were included in the study. A significant difference between the "septic" and "non-septic" groups was detected in the NEUT-RI plasma concentration (53.80 [49.65–59.05] vs. 48.00 [46.00–49.90], p< 0.001, respectively). NEUT-RI and PCT distinguished between not complicated sepsis and septic shock (PCT 1.71 [0.42 - 12.09] vs 32.59 [8.83 - 100.00], < 0.001 and NEUT-RI 51.50 [47.80 - 56.30] vs 56.20 [52.30 - 61.92], p=0.005). NEUT-RI, PCT and CRP values were significantly different in patients with “renal failure”. NEUT-RI and PCT at admission in ICU in septic group were higher in patients who died (58.80 [53.85-73.10] vs 53.05 [48.90-57.22], p=0.005 and 39.56 [17.39-83.72] vs 3.22 [0.59-32.32], p=0.002, respectively). Both NEUT-RI and PCT showed high negative predictive value and low positive predictive value. Conclusions: The inflammatory biomarkers assessed in this study offer valuable support in the early diagnosis of sepsis. NEUT-RI elevation appears particularly promising for early sepsis detection and severity discrimination upon admission

Extensive genomic analyses of Enterococcus cecorum isolates from sepsis outbreaks in broilers suggests a polyphyletic origin likely arising from core genome mutations rather than gene acquisition. This species is normal intestinal flora in avian species with particular isolates associated with osteomyelitis. More recently, the species has been associated with sepsis outbreaks affecting broilers during the first 3 weeks post hatch. Understanding the genetic and management basis of this new phenotype is critical for developing strategies to mitigate this emerging problem. Phylogenomic analyses of 227 genomes suggest that sepsis isolates are polyphyletic and closely related to both commensal and osteomyelitis isolate genomes. Pangenome analyses detect no gene acquisitions that distinguish all sepsis isolates. Core genome SNP analyses identify a number of mutations, affecting protein coding sequence, that are enriched in sepsis isolates. Analysis of the protein substitutions supports mutational origins of sepsis isolates.

Monomeric Ubiquitin (Ub) is a 76-amino acid highly conserved protein found in eukaryotes. The first described biological activity of Ub in the 1970s was extracellular, but it quickly gained relevance due to its intracellular role, i.e., post-translational modification of intracellular proteins (ubiquitination) that regulate numerous eukaryotic cellular processes. In the following years, the extracellular role of Ub was relegated to the background, until a correlation between higher survival rate and increased serum Ub concentrations in patients with sepsis and burns was observed. Although the mechanism of action (MoA) of extracellular ubiquitin (eUb) is not yet well understood, further studies have shown that it may ameliorate the inflammatory response in tissue injury and multiple sclerosis diseases. These observations compounded with the high stability and low immunogenicity of eUb due to its high conservation in eukaryotes have made this small protein a relevant candidate for biotherapeutic development. Here, we review the in vitro and in vivo effects of eUb on immunologic, cardiovascular, and nervous systems, and discuss the potential MoAs of eUb as an anti-inflammatory, antimicrobial, cardio- and brain-protective agent.

Early treatment is the mainstay of sepsis therapy. We suspected that early recognition of sepsis by prehospital healthcare providers may shorten time to antibiotic administration in the Emergency Department. We retrospectively evaluated all patients above 18 years of age that were diagnosed with sepsis or severe infection in our Emergency Department between 2018 and 2020. We recorded the suspected diagnosis at time of presentation, type of referring healthcare provider and time until initiation of antibiotic treatment. Differences between groups were calculated using Kruskal-Wallis rank sum test. Of the 277 patients that were diagnosed with severe infection or sepsis in the emergency department, an infection was suspected in 124 (44.8%) patients and sepsis was suspected in 31 (11.2%) patients by referring healthcare providers. Time to initiation of antibiotic treatment was shorter in patients where sepsis or infection had been suspected prior to arrival for both patients with severe infections (p = 0.022) and sepsis (p = 0.004). Given the well described outcome benefits to early sepsis therapy, recognition of sepsis needs to be improved. Appropriate scores should be used as part of routine patient assessment to reduce time to antibiotic administration and improve patient outcomes.

Identifying a panel of markers detecting kidney injury before the glomerular filtration rate (GFR) reduction is the challenge to improve the diagnosis and the management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase, insulin growth factor binding protein (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in AKI patients. Patients and Methods: This study was prospectively conducted in the Intensive Care Unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 hours of the cardiac surgery. Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7 – 36.5) hours, after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 hours in AKI patients (1.1±0.4 mg/l vs 0.08±0.02 mg/l; p < 0.001). Its concentration >2 mg/l increases the AKI risk within the following 24 hours, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/l (0.7–7.8 nmol/l), with the highest values observed in septic shock [5.6 nmol/l (3.2–18 nmol/l)] and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values >5.1 nmol/l and urine TIMP2*IGBP7 levels > 2 mg/l showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. Conclusions: TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

Community-acquired pneumonia (CAP) is among the most common causes of death and one of the leading healthcare concerns worldwide. It can evolve into sepsis and septic shock, which have a high mortality rate, especially in critical patients and comorbidities. The definitions of sepsis were revised in the last decade as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. Procalcitonin (PCT), C-reactive protein (CRP), and complete blood count including white blood cells are among the most commonly analyzed sepsis-specific biomarkers also used in pneumonia in a broad range of studies. It appears to be a reliable diagnostic tool to expedite care of these patients with severe infections in the acute setting. PCT was found superior to most other acute phase reactants and indicators, including CRP as a predictor of pneumonia, bacteremia, sepsis and poor outcome. In addition, PCT use is beneficial to judge timing for cessation of antibiotic treatment in most severe infectious states. The clinicians should be aware of strengts and weaknesses of known and potential biomarkers in expedient recognition and management of severe infections. This manuscript is intended to present an overview of the definitions, complications and outcomes of CAP and sepsis, with special regard to PCT and other important markers.

We present a case of Capnocytophaga canimorsus septic shock after a dog bite in an immunocompetent individual, where real-time nanopore metagenomic sequencing characterized the microbial agent within 19 hours, with subsequent confirmation using droplet digital PCR. Oral swabs from the dog demonstrated a nearly-identical C. canimorsus isolate by sequencing.

Sepsis is a devastating disease that carries an enormous toll in terms of human suffering and lives lost. Over 100 novel pharmacologic agents which targeted specific molecules or pathways have failed to improve the outcome of sepsis. Preliminary data suggests that the combination of Hydrocortisone, Ascorbic Acid and Thiamine (HAT therapy) may reduce organ failure and mortality in patients with sepsis and septic shock. HAT therapy is based on the concept that a combination of readily available, safe and cheap agents which target multiple components of the host’s response to an infectious agent will synergistically restore the dysregulated immune response and thereby prevent organ failure and death. This paper reviews the rationale for HAT therapy with a focus on vitamin C.

Background: Detection of small proportion of serious bacterial infections (SBI) with potentially life threating course in a large group of children with fever admitted to emergency department (ED) is still complicated. Measurement of immature granulocytes (IG) percentage may be used as a marker of bacterial infections. The aim of the study was to evaluate whether the IG percentage is a useful additional predictive marker of SBI. Methods: This study included 258 children with febrile infections admitted to the ED. Clinical follow-up, microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (i) infected patients with no suspicion of SBI (n = 75); (ii) patients with suspicion of SBI (n = 183). IG percentage, white blood cell count (WBC) and C-reactive protein (CRP) levels were analyzed from the first routine blood samples at hospital admission. Results: A statistically significant difference in IG percentage levels was observed in children with SBI and those without - the mean IG percentage was 1.2% for the SBI group, 0.3% for those without SBI. The cutoff level of IG percentage to predict SBI was 0.45 (84% specificity, 66% sensitivity, 90% positive predictive value). We combine variables and evaluate their additive values. The sensitivity of WBC to detected SBI improved from 74% to 85% when IG percentage was added to the prediction models. When CRP, WBC and IG percentage were combined, the sensitivity to predict SBI increased to 93%, the specificity to 86%. (95% CI 77–93%). Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.80 for IG percentage. Conclusion: Addition of IG percentage to traditionally used markers of SBI as WBC and CRP may help to identify children with serious bacterial infections. Furthermore IG percentage can be rapidly obtained from the traditional full blood count without any extra sampling and costs.

Abstract: High-dose-rate interstitial brachytherapy (HDR-ISBT) has recently come to be considered one of the most effective treatments for oral cancer. On the other hand, it is important to note that radiation therapy has some side effects. Especially, radiation-induced malignancy is probably the most serious complication affecting long-term survivors. We report a case of a radiation-induced undifferentiated spindle cell sarcoma that developed following HDR-ISBT for tongue squamous cell carcinoma (SCC). A 39-year-old woman with right tongue SCC underwent HDR-ISBT (60 Gy, 10 fractions, 8 days) treatment. Five years and one month later, a tumor had developed at the primary site. Surgery was performed for the tumor, which was histopathologically diagnosed as an undifferentiated spindle cell sarcoma. That was distinct from the squamous cell origin of the primary cancer. According to recently established criteria for radiation-induced malignancy, this case was classified as a radiation-induced sarcoma. A search of the literature revealed no previous report of radiation-induced malignancy following HDR-ISBT for tongue cancer.

We present the case of a 28-year-old male with a history of alcohol dependency and smoking, who presented with chest pain, shortness of breath, and altered sensorium. He exhibited severe metabolic acidosis, low platelet count, and acute kidney injury. Alcoholic ketoacidosis (AKA) was suspected due to ketonuria, metabolic acidosis, and ketonemia, compounded by electrolyte abnormalities and radiographic findings of pneumonia.Prompt intervention included electrolyte correction, thiamine supplementation, broad-spectrum antibiotics, and diuretics. Thiamine played a pivotal role in the patient's recovery, with significant improvement in consciousness observed within a day. After six days, the patient was discharged in stable condition, showing normal renal and hepatic function during follow-up.This case emphasizes the need for early recognition and comprehensive management in AKA, highlighting thiamine's crucial role in treatment success.

Early diagnosis and appropriate treatments are crucial to reducing mortality risk in septic patients. Low SOFA scores and current biomarkers may not discern adequately patients that could develop severe organ dysfunction or have an elevated mortality risk. The aim of this prospective observational study is to evaluate the predictive value of the biomarkers midregional proadrenomedullin (MR-proADM), procalcitonin (PCT), C-Reactive Protein (CRP), and lactate for 28-day mortality in patients with sepsis and a SOFA score ≤ 6. 284 patients were included, with a 28-day all-cause mortality of 8.45 % (N=24). Non-survivors were older (p=0.003), required mechanical ventilation (p=0.04) and were ventilated for longer (p=0.02), had a higher APACHE II (p=0.015) and SOFA (p=0.027) scores. Lactate showed the highest predictive ability for all-cause 28-day mortality with an area under the receiver-operating characteristic curve (AUROC) of 0.67 (0.55–0.79). The AUROC for all-cause 28-day mortality in patients with community-acquired infection was 0.69 (0.57–0.84) for SOFA, and 0.70 (0.58–0.82) for MR-proADM. A 2.1 nmol/L cut-off point for this biomarker in this subgroup of patients discerned with 100% sensibility survivors from non-survivors at 28 days. In patients with community acquired sepsis and initial SOFA score ≤ 6, MR-proADM could help identify patients at risk of 28-day mortality.

Purpose: To reassess the results of former meta-analyses focusing on the relationship between novel HES preparations (130/0.4 and 130/0.42) and acute kidney injury. Previous meta-analyses are based on studies referring to partially or fully unpublished data or data from abstracts only. Methods: The studies included in the former meta-analyses were scrutinized by the authors independently. We completed a critical analysis of the literature, including the strengths, weaknesses and modifiers of the studies when assessing products, formulations and outcomes. Results: Both the published large studies and meta-analyses show significant bias in the context of the deleterious effect of 6% 130/0.4-0.42 HES. Without (1) detailed hemodynamic data, (2) the exclusion of other nephrotoxic events and (3) a properly performed evaluation of the dose-effect relationship; the AKI-inducing property of 6% HES 130/0.4 or 0.42 could not be accounted as evidence. The administration of HES is safe and effective if the recommended dose is respected. Conclusion: Our review suggests that there is questionable evidence for the deteriorating renal effect of these products. Further well-designed, randomized and controlled trials are needed. Further conclusions formulated for resource-rich environments should not be extended to more resource-scarce environments without proper qualifiers provided.

Life evolved in an euxinic world with subsequent oxic 'invasion' leading to two parallel but interconnected biospheres, hydrogen sulphide (H₂S) and hydrogen peroxide (H₂O₂) exemplify these worlds respectively. Their concentration gradients have informational value in meromictic lakes. Similarly, it is posited, there exists a whole body chemocline in humans in which the two molecules form an inversely coupled oxic/sulphidic oscillator (OSO). The OSO is hormetic and characterised by a range of amplitudes and frequencies in health. Deviations from its baseline profile heralds the onset of SIRS before the appearance of clinical signs. Loss of oscillator status and transition to a steady state causes widespread intercellular and inter-organ communication failure presaging multi-organ dysfunction. The salient clinico-pathophysiological features of SIRS of any aetiology are emergent phenomena related to the OSO profile. Extent of recovery of organ function will mirror the recovery of the OSO profile thereby providing a tool to predict outcomes in SIRS.

Purpose: To assess the clinical safety and possible effectiveness of Vasoactive Intestinal Peptide in the treatment of Acute Respiratory Distress Syndrome (ARDS) related to sepsis. Methods: Under FDA Investigational New Drug clearance, 8 patients with ARDS related to sepsis were treated with 50 pmole/kg/hr – 100 pmole/kg/hr of Vasoactive Intestinal Peptide by intravenous infusion for 12 hours. All patients were on mechanical ventilation and full telemetery. Results: No drug-related serious adverse events were seen. Hypotension was seen in association with two infusions and diarrhea in association with one, but did not necessitate cessation of therapy. Bigeminy was seen in association with one infusion without sequelae. Seven of eight patients demonstrated a successful course during intensive care and were successfully removed from mechanical ventilation and discharged from intensive care. The eighth patient succumbed to purulent secretions in the lungs. Of those who were discharged from the ICU, six demonstrated successful 30 day survival. The seventh died from a cerebral infract at day 30, deemed unrelated to treatment with VIP. Serum levels of Tumor Necrosis Factor α were obtained in 6 patients at baseline and 24 hours and were seen to decrease with treatment in five patients. Conclusions: Initial clinical results of treatment with VIP in patients with ARDS demonstrated a safety profile consistent with previous studies in normal volunteers. The successful clinical course seen in 7 of 8 patients in the setting of an expected 50% survival may suggest that VIP shows promise in the treatment of other infectious conditions that damage the pulmonary epithelium, particularly COVID-19.

Aim: Aim of our study to evaluate various factors responsible for surgical site infection after gastrointestinal and hepatobiliary surgeries. Material and Methods: Patient who underwent gastrointestinal and hepatobiliary surgery in our department were evaluated retrospectively. Various factors associated with surgical site infection were evaluated using univariate and multivariate analysis. Surgical site infection was defined as any culture positive discharge from the wound within 30 days of surgery.Statistical analysis was done using SPSS version 23. Results: We evaluated total 331 patients operated between April 2018 to March 2020. 14 patients were lost to follow up after discharge and before completing post operative day 30. 18 patients expired before 30 days without developing SSI and were excluded from the study as per exclusion criteria. 299 patient included in the study. Total 20 patients developed surgical site infection. It showed SSI rate in our study population was 6.68%. On univariate analysis prolonged hospital stay, more blood product used, higher cdc grade of surgery, higher ASA grade, more operative time, open surgeries,colorectal and HPB surgeries were associated with surgical site infections. On multivariate analysis only prolonged hospital stay independently predicted Surgical Site Infectins. (p=0.014,0dds ratio 1.223, 95% confidence interal 1.042-1.435). Conclusion: Prolonged hospital stay independently predicts surgical site infections after gastrointestinal and hepatobiliary surgery.

Diagnosis of neonatal sepsis is difficult as signs and symptoms are nonspecific. Interleukin-6 (IL-6) is a promising marker for neonatal sepsis. We aimed to test the accuracy of IL-6 in term and preterm infants after 72 hours of life (late-onset sepsis-LOS). We searched for IL-6 diagnostic accuracy studies between 1990 and 2020 using the PubMed database. Study selection was performed. The range of reported IL-6 sensitivities and specificities was 68% to 100% and 28% to 100%, respectively, the median values were 85.7% and 82% from 15 studies including 1306 infants. Subgroup analysis was performed. Sensitivity (87% vs 82%), but not specificity (both 86%), was better in preterm infants than in preterm and term infants. Early sample collection had the highest sensitivity (84%), but the lowest specificity (86%). To assess quality we used a STARD checklist adapted for septic neonates. Limitation of this review include the heterogeneous group of studies on the one side and the small number of studies on the other side that analyzed different combinations of biomarker. We concluded that IL-6 had a good performance especially in the preterm infant population and best results are achieved by measurements at the time of LOS suspicion.

Human sepsis is one of the leading cause of death worldwide and is known to be a harmful damaging host inflammatory condition, primarily caused by endotoxin released by gram-negative bacteria. Despite antibiotics administration being widely used to treat disease, effective targeted therapeutic strategies for the sepsis are still lacking. Here, we demonstrate that CM1, a derivative of natural polyphenol chrysin, exerts anti-inflammatory activity by inducing the ubiquitin-editing protein TNFAIP3 and NAD-dependent deacetylase sirtuin 1 (SIRT1). We found that CM1 attenuated Toll-like receptor 4 (TLR4)-induced the generation of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signaling pathway. In addition, the treatment of macrophages with CM1 induced the expression of TNFAIP3 and SIRT1 in TLR4-stimulated primary macrophages, however the anti-inflammatory properties of CM1 was disappeared by siRNA silencing of TNFAPI3 or by the genetic and pharmacologic inhibition of SIRT1. Importantly, intravenously administration of CM1 resulted in the decreased susceptibility to endotoxin-induced sepsis, leading to inhibition of the generation of proinflammatory cytokines and neutrophils infiltration into lung than control mice. Collectively, these findings suggest that CM1 has the potential to be a treatment candidate for diverse inflammatory diseases including sepsis.

Keywords: Cell-free DNA, sepsis, oxidative stress, immunoredox modulation, cecal ligation and puncture, toll-like receptor

Background. It is well established that human milk feeding contributes in limiting lung disease among vulnerable neonates. The primary aim of this research was to compare the need for mechanical ventilation of human milk-fed sick neonates with that of formula-fed sick neonates. Methods. All late preterm and full term infants from a single center with findings of sepsis, from 2002 to 2017, were identified. Data regarding infant feeding during hospital admission were recorded. Multivariate logistic regression analyses were performed to assess the impact of the type of milk on ventilation support and main neonatal morbidities. Results. The total number of participants was 322 (human milk group = 260, exclusive formula group = 62). On bivariate analysis, 72% of human milk-fed neonates did not need oxygen therapy nor respiratory support versus 55% of their formula-fed counterparts (P<0.0001). Accordingly, invasive mechanical ventilation was required by 9.2% of human milk-fed infants versus 32% of their formula-fed counterparts (P=0.0085). These results hold true in multivariate analysis, indeed human milk-fed neonates were more likely to require less respiratory support (OR=0.44; 95% CI: 0.22, 0.89) when compared to those who were exclusively formula-fed. Conclusion. Human milk feeding might minimize exposure to mechanical ventilation.

Psychosis can be defined as a combination of psychopathological symptoms including delusions and/or hallucinations without insight. Psychotic disorders may configure a primary psychiatric illness or represent the result of a functional/structural brain damage induced by substance use, neurological diseases or other medical conditions. They are multifactorial disorders in which genetic, environmental and gene-environment interaction factors contribute to the expressiveness of the symptoms. Among the environmental factors, psychotropic substances represent the most important removable facilitators of psychosis. In our study, we compared the prevalence of substance induced psychosis between a sample of patients affected by cannabis use disorder and a sample of patients affected by cocaine use disorder analyzing retrospectively the data of outpatients with no personal or family history of psychiatric illnesses.

Drug induced liver injury (DILI) is the most common cause of acute liver failure and 5-10% of patients hospitalized for jaundice are diagnosed with DILI. For a diagnosis of DILI to be made, there should be exclusion of other etiologies of liver injury and the use of a precipitator drug, latency of symptoms, and resolution of liver injury once the offending drug is identified and discontinued. In our case report, we present a patient with idiosyncratic hepatocellular pattern DILI after two doses of ocrelizumab for treatment of multiple sclerosis. Ocrelizumab was given 16 and 27 days prior to the onset of icterus, jaundice, and fatigue, in a patient without the evidence of prior exposure to hepatitis B virus. At presentation labs revealed severe acute hepatocellular liver injury with R factor of 30.42, marked hyperbilirubinemia, and transient hypoalbuminemia. No evidence of latent or active hepatitis B infection was detected. Drug dechallenge led to return of liver chemistries to near-normal levels 31 days after the onset of her symptoms. This case indicates DILI diagnosis associated with the use of ocrelizumab, and warrants careful monitoring of liver functions in patients even in the absence of hepatitis B.

In resettlement planning literature, much has been written on economic, land valuation and compensation, infrastructure and services aspects of the land. Psychological risks and stresses of resettled communities, however, have been under-researched. The current research looks at the psychological risks of resettlers in a Development-Induced Displacement and Resettlement (DIDR) project in Sri Lanka. Focusing on the stages of resettlement planning process discussed by Scudder and Colson four-stage model (1980) and the psychological risks discussed by Cernea’s (1990) impoverishment risks and reconstruction (IRR) model. This study evaluates the significant level of the psychological risks faced by the communities in DIDR projects in Sri Lanka relating to before and after resettlement. Moragahakanda Resettlement Project (MRP) was selected as the case study which is located in Naula DS division of Matale District, Central Province, Sri Lanka. A questionnaire survey, documents and field observations were used to evaluate the current psychological risks. The responses received from multiple choice questions were analyzed by Significant Point (SP) index. The research findings point that there are no conspicuous changes of psychological risks related to before/after resettlement has occurred in re-settlers. The findings highlight that the psychological risk levels in transition stage have remained the same level in the potential development stage. This research provides a systematic guidance enabling the physical planners to prioritize the most significant psychological risks which should be considered in the decision-making process of DIDR projects.

Background: The morbidity of myocardial infarction is keeping raise in this decade. Because of high safety and operability , percutaneous coronary intervention(PCI) has been used to conquer this disease for more than 20 years.An important complication of PCI is contrast induced nephropathy(CIN), which raises our attention. Previously, we started a study to explore the correlation between acute kidney injury and myonecrosis after scheduled percutaneous coronary intervention. Our study showed that the rate of CI-AKI in patients with post-procedural myocardial injury and undergoing elective PCI was higher than that in patients free of injury. Methods: In this study,forty male rats were randomly divided into four groups: control group (n=8), CM group (n=12), AMI group (n=8) and AMI+CM group (n=12), then velocity of renal artery blood flow (VRABF), computer tomography (CT), serum creatinine(Scr), reactive oxidative species (ROS), periodic acid-Schiff (PAS) and TUNEL were used to estimate the injury of kidney. We analyzed 327 non-ST-segment elevation acute coronary syndrome subjects undertaking elective PCI. Serum levels of creatinine (SCr) and the eGFR before coronary angiography, and 24–72 h after contrast administration were recorded to assess the renal function. Results: The data showed that VRABF was lower in AMI+CM group than CM group from 0 minute to 24h and CT number in cortex was higher in AMI+CM group than CM group at 4-hour. As well as the level of Scr in AMI+CM group displayed a significantly increase at 24-hour compared with CM group. The histopathologic scores and percentage of tubular cell apoptosis were higher in AMI+CM group at 24-hour. In 327 patients, we found that CI-AKI occurred more often in subjects with post-procedural myonecrosis (PMN) than in those without PMN (20.8% versus 5.8%, respectively, P=0.001). Conclusion: Compared to the elective patient, the injury of CIN exhibited a higher severity in AMI patient.

The tension cable-supported power transmission structure (TC-PTS) is a new type of power transmission structure suitable for mountainous terrain, which is sensitive to wind load. In this regard, a nonlinear finite element analysis model of wind-induced vibration is proposed for the TC-PTS, and the wind-induced vibration response of the structure is analyzed. Firstly, the tangent stiffness matrix of the three-dimensional truss element for the supporting suspension cable and transmission line, considering the geometric nonlinearity of structures, is derived through the relationship between the element elastic energy and its displacement. Subsequently, the element mass matrix and damping matrix of the supporting suspension cable and transmission line, as well as the element nodal load vector obtained from wind load equivalence are given. Then, based on the nonlinear finite element theory, the nonlinear dynamic equation of wind-induced vibration is established for the TC-PTS and solved by Newmark-β method combined with Newton-Raphson iterative method. Furthermore, the rain-flow counting method and Miner's linear fatigue cumulative damage theory were used for wind induced fatigue damage assessment. Finally, a two-span TC-PTS is selected as an example, and the wind-induced nonlinear vibration and fatigue damage assessment are analyzed through the proposed model. The results show that the proposed model has high computational accuracy and efficiency. With the increase of wind speed and wind direction angle, the maximum lateral displacement and tension of the supporting suspension cable and transmission line increase, and their degree of increase shows a nonlinear trend. In terms of the wind-induced fatigue analysis results of TC-PTS, the fatigue damage at the end of the supporting-conductor suspension cable is greater than the fatigue damage at its midpoint. Compared to the fatigue damage at the midpoint of the conductor, the fatigue damage at the end of the conductor is less affected by wind direction angle, and both are more significantly affected by the wind speed.

This paper presents Mathematical Formulation for Neutrino-Fission of a heavy nuclei in Neutrino-environments. It has been proposed that neutrino fission is a dynamic two-process reaction, where more than one neutrino can be captured by target nucleus. A quantity named Neutrino-Zeta with units of eV^-1 has been defined to represent Neutrino-environments. Neutrino-zeta with assumed excited energy states for heavy nuclei A∼230-270 is estimated to be 0.0212 MeV^-1, with the probability of fission Barrier energy state P(E_x,f)= 0.169064014 with E_x,f =6MeV. P(E_x,f)=0.222664 is highest at zeta=0.1MeV^-1 . It has been shown that probabilities of certain excitation energy states and their corresponding decay reactions at those excitation energies can be equal for two neutrino-zetas. Neutron induced fission for different neutrinos hypothesize that probability of symmetric fission channels is higher at low neutrino-zetas, which can be tested experimentally.

Spatially resolved, line-of-sight measurements of aluminum monoxide emission spectra in laser ablation plasma are used with Abel inversion techniques to extract radial plasma temperatures. Contour mapping of the radially deconvolved signal intensity shows a ring of AlO formation near the plasma boundary with the ambient atmosphere. Simulations of the molecular spectra were coupled with the line profile fitting routines. Temperature results are presented with simultaneous inferences from lateral, asymmetric radial, and symmetric radial AlO spectral intensity profiles. This analysis indicates that we measured shockwave phenomena in the radial profiles, including a temperature drop behind the blast wave created during plasma initiation.

(1) Background: Neonatal early-onset sepsis (EOS) is associated with important mortality and morbidity. The aims of this study were to evaluate the association between serum biomarkers with early onset neonatal sepsis in a cohort of patients with prolonged rupture of membranes (PROM), and to calculate their diagnostic accuracy. (2) Methods: A retrospective cohort study was conducted on 1355 newborns with PROM admitted between January 2017 and March 2020, who were divided in two groups: group A, with PROM ≥ 18 hours and group B, with PROM < 18 hours. Both groups were further split into subgroups: proven sepsis, probable sepsis and no sepsis. Descriptive statistics, ANOVA analysis, and a Random Effects Generalized Least Squares (GLS) regression were used to evaluate the data. (3) Results: The statistically significant predictors of neonatal sepsis were the high white blood cells count from the first (p = 0.005) and third day (p = 0.028), and high CRP values from the first day (p = 0.004). Procalcitonin (area under the curve - AUC = 0.78) and CRP (AUC = 0.76) measured on the first day had the best predictive performance for early onset neonatal sepsis. (4) Conclusions: Further studies are needed to explore other bi-omarkers of sepsis in both pregnant women and newborns to better predict EOS.

Background The Delta Neutrophil Index (DNI), a prodiagnostic marker for sepsis, utilizes leukocyte count. Platelet activation, similar to leukocytes, plays a crucial role in host defence against pathogens and may serve as a predictor of sepsis outcome. However, the combined evaluation of Mean Platelet Component (MPC) and DNI in assessing sepsis has been rarely used. Methods To assess the prodiagnostic validity of simultaneous utilization of DNI and MPC in cases of human febrile sepsis, we conducted measurements of cellular indices, including DNI and MPC, as well as molecular biomarkers such as procalcitonin (PCT) and C-reactive protein (CRP). This study was carried out on patients admitted to the emergency department with suspected sepsis. Results Using a cutoff value of 2.65%, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DNI in sepsis were found to be 69%, 73.9%, 77.9%, and 64.1%, respectively. Furthermore, significant differences in DNI and MPC levels were observed between the sepsis and non-sepsis groups (6.7±7.8% versus 2.1±2.2%, P=0.000 and 26.0±1.9 g/dl versus 26.8±1.4 g/dl, P=0.002), respectively. Notably, there was a negative correlation between DNI and MPC, with the strength of the correlation varying based on the cause of sepsis. By setting the cutoff value for DNI at 6.2%, the sensitivity, specificity, and NPV improved to 100%, 80.3%, and 100%, respectively, although the PPV remained at 10.6%. Importantly, the DNI≥6.2 group exhibited a higher incidence of death (10.9%, 5/46) and multiorgan failure (19.6%, 9/46) compared to the DNI<6.2 group (0.0%, 0/46 and 0.0%, 0/167, respectively) (P=0.000 and P=0.000, respectively). Conclusions In our study, DNI demonstrates superior effectiveness compared to other molecular biomarkers such as CRP and procalcitonin in distinguishing febrile septic patients from febrile nonseptic patients and predicting prognosis. Additionally, there exists a negative correlation between MPC and DNI, making MPC a valuable marker for differentiating the etiology of sepsis. These findings hold significant clinical implications as DNI/MPC is a cost-effective and readily applicable approach in various impending sepsis scenarios. Notably, this study represents the first examination of the prodiagnostic validity of simultaneously employing DNI and MPC in human cases of febrile sepsis.

Abstract: Background: Neonatal sepsis continues to be one of the leading causes of mortality and morbidity, particularly in under development and underdeveloped countries. We aim to compare laboratory parameters between the early-onset sepsis (EOS) and non-EOS groups and to evaluate the association between TLR2- Arg753Gln, TLR4 -Asp299Gly, IL6-174G/C and IL10-1082G/A gene single nucleotide polymorphisms and EOS susceptibility in preterm newborns. Methods: Genotyping of the TLR2, TLR4, IL6 and IL10 polymorphisms was performed in 36 preterm neonates by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP). Logistic regression analysis was used to test the associations between the studied gene polymorphisms and EOS susceptibility. Results: Statistically significant differences in gestational age and birth weight were observed between the two groups, preterm neonates with EOS having a lower mean of gestational age (weeks, 29.4 ± 2.8 versus 32.6 ± 1.1, p = 0.00002) and lower mean of birth weight (gr., 1342.1 ± 446.5 vs. 1984 ± 376.9) than preterm neonates without EOS. C-reactive protein (CRP) values measured at first day significantly increased in EOS group compared with non-EOS group (median, 95% CI: 0.80 [0.40, 1.15] versus 0.30 [0.02, 0.50]). Mean of neutrophils significantly decreased in the EOS preterm neonates (mean difference: 17.3%, 95% CI: [4.0%, 30.5%], p = 0.0126) and non-EOS group (mean difference: 20.8%, 95% CI: [1.8%, 39.9%, p = 0.0354) between the first day and 7th hospitalization day. The minor IL10-A1082 allele frequency was higher in the EOS group than in the nonEOS group (50% versus 25%) with a marginal statistical significance (p=0.0550). In the dominant model, the A/G + A/A variant genotype of IL10- 1082G/A polymorphism significantly increased the odds of EOS compared with GG genotype (OR= 5.25, p = 0.0322). Conclusions: The results of the current study suggests the IL10- 1082G/A gene polymorphism as significant risk factor for early onset sepsis development in preterm neonates.

Sepsis is a life-threatening condition caused by the body's overwhelming response to an infection, such as pneumonia or urinary tract infection. It occurs when the immune system releases cytokines into the bloodstream, triggering widespread inflammation. If not treated, it can lead to organ failure and death. Unfortunately, sepsis has a high mortality rate, with studies reporting rates ranging from 20% to over 50%, depending on the severity and promptness of treatment. According to the World Health Organization (WHO), the annual death toll in the world is about 11 million. One of the main toxins responsible for inflammation induction are lipopolysaccharides (LPS, endotoxin) from Gram-negative bacteria, which ranks among the most potent immunostimulants found in nature. Antibiotics are consistently prescribed as a part of anti-sepsis-therapy. However, antibiotic therapy (i) is increasingly ineffective due to resistance development and (ii) most antibiotics are unable to bind and neutralize LPS, a prerequisite to inhibit the interaction of endotoxin with its cellular receptor complex, namely Toll-like receptor 4 (TLR4)/MD-2, responsible for the intracellular cascade leading to pro-inflammatory cytokine secretion. The pandemic virus SARS-CoV-2 has infected hundreds of millions of humans worldwide since its emergence in 2019. The COVID-19 (Coronavirus disease-19) caused by this virus is associated with high lethality, particularly for elderly and immunocompromised people. As of August 2023, nearly 7 million deaths were reported worldwide due to this disease. According to some reported studies, upregulation of TLR4 and the subsequent inflammatory signaling detected in COVID-19 patients “mimics bacterial sepsis”. Furthermore, the immune response to SARS-CoV-2 was described by others as “mirror image of sepsis”. Similarly, the cytokine profile in sera from severe COVID-19 patients was very similar to those suffering from the acute respiratory distress syndrome (ARDS) and sepsis. Finally, the severe COVID-19 infection was frequently accompanied by bacterial co-infections, as well as by the presence of significant LPS concentrations. These data indicate similarity and interdependences of both syndromes, but also significant differences which will be discussed in the present review.

Presepsin is a diagnostic and prognostic biomarker of sepsis; however, elevated presepsin levels have also been documented without sepsis. This study aims to retrospectively analyze the laboratory parameters and Sequential Organ Failure Assessment (SOFA) score affecting presepsin levels in 567 patients. Some patients with elevated presepsin levels exhibited renal dysfunction or elevation of biliary enzymes despite a low SOFA score. The univariate regression analysis revealed a close correlation between presepsin levels and SOFA score, serum creatinine (CRE), blood urea nitrogen, and biliary enzymes. In addition, a multivariate regression analysis revealed that SOFA score, alkaline phosphatase (ALP), and CRE independently affected presepsin levels significantly. The analysis of covariance (ANCOVA) revealed that presepsin levels were significantly higher in patients with hepatobiliary disease. Besides, we found that patients who presented with the dilatation of intra- or extrahepatic bile ducts and the elevation of ALP or total bilirubin exhibited remarkable high presepsin levels in the bile. Furthermore, the presepsin production in the liver’s Kupffer cells was established by immunostaining in patients who received surgical liver resection. Overall, this study elucidates that biliary enzymes’ elevation affects presepsin levels, presepsin exists in high concentrations in the bile, and is positive in Kupffer cells.

Biomimetic design has recently received widespread attention. Inspired by the Terebridae structure, this paper provides a structural form for suppressing vortex-induced vibration (VIV) response. Four different structural forms are shown, including the traditional smooth cylinder (P0), the Terebridae-inspired cylinder with a helical angle of 30° (P30), the Terebridae-inspired cylinder with a helical angle of 60° (P60), and the Terebridae-inspired cylinder with a helical angle of 90° (P90). And computational fluid dynamics (CFD) method is adopted to solve the flow pass the Terebridae-inspired structures, and the vibration equation is solved using the Newmark-β method. The results show that the VIV responses are effectively controlled in the lock-in region for P30, P60, and P90, and P60 shows the best VIV suppression performance. The transverse amplitude and the downstream amplitude can be reduced by 82.67% and 91.43% respectively for P60 compared with that for P0, and the peak of the mean-drag coefficient is suppressed by 53.33%. The Q-criterion vortices of P30, P60, and P90 are destroyed, with irregular vortices shedding. It is also found that the boundary layer separation is located on the Terebridae-inspired ribs. The twisted ribs cause the separation point to constantly change along the spanwise direction, resulting in the development of the boundary layer separation being completely destroyed. The strength of the wake flow is significantly weakened for the Terebridae-inspired cylinder. In the lock-in region, the motion trajectory presents a typical 8-shaped for P0, while the motion trajectory of the Terebridae-inspired cylinder tends to be a flat 1-shaped.

Trichoderma spp. are widely used in plant disease control as biocontrol agents. Inducing plant disease resistance is an important biocontrol mechanism of Trichoderma. It is of great significance to explore the factors involved in the surface recognition and interaction of Trichoderma with plants. Hydrophobin is a small molecular protein rich in cysteine in higher filamentous fungi and has been found to participate in the morphogenesis and interaction of fungi with other organisms. In this study, the type II hydrophobic protein-coding gene Thfb6 from T. harzianum TH33 was cloned and heterologously expressed in Escherichia coli BL21 (DE3). The purified recombinant protein Thfb6 induced a hypersensitive response in tobacco leaves, a burst of reactive oxygen species, and an accumulation of callose, phenolic substances, and lignin in tobacco, indicating that Thfb6 can induce an early defense reaction in tobacco. Thfb6 also enhanced the systemic resistance of tobacco against tobacco mosaic virus. The rate of lesion number reduction by treatment with Thfb6 could be up to 36.02%. Thfb6 increased the activity of tobacco defense-related enzymes, including phenylalanine ammonia-lyase (PAL), polyphenol oxidase, and peroxidase, which were all more than three times the control after 3–5 days post treatment of Thfb6. The transcription of resistance-related genes, including the PAL gene, non-expresser of pathogenesis-related gene1 (NPR1), and basic pathogenesis-related gene 1 (PR1-b), were upregulated after Thfb6 treatment. The relative expression levels of the PAL and NPR1 genes were highest on the third and fourth days after Thfb6 treatment, at 5.5 times and 8.3 times that of the control, respectively. The relative expression level of PR1 on the sixth day after Thfb6 treatment was 5.3 times that of the control. These results indicate that the improvement of defense-related enzyme activity and the induced expression of disease-resistance-related genes were the main mechanisms by which Thfb6 induced systemic resistance in tobacco.

Fusarium wilt diseases severely influence the growth and productivity of numerous crop plants. The consortium of antagonistic rhizospheric Bacillus strains and quercetin were evaluated imperatively as a possible remedy to effectively manage the Fusarium wilt disease of tomato plants. The selection of Bacillus strains was made based on in-vitro antagonistic bioassays against Fusarium oxysporum f.sp. lycoprsici (FOL). Whereas, quercetin was selected after screening a library of phytochemicals during in-silico molecular docking analysis using tomato LysM receptor Kinases “SILKY12” based on its dual role in symbiosis and plant defense responses. After the selection of test materials, pot trials were conducted where tomato plants were provided consortium of Bacillus strains as soil drenching and quercetin as a foliar spray in different concentrations. The combined application of consortium () and quercetin (1.0 mM) reduced the Fusarium wilt disease index up to 69% also resulting in increased plant growth attributes. Likewise, the imperative application of the Bacillus consortium and quercetin (1.0 mM) significantly increased total phenolic contents and activities of the enzymes of the phenylpropanoid pathway. Non-targeted metabolomics analysis was performed to investigate the perturbation in metabolites. FOL pathogen negatively affected a range of metabolites including carbohydrates, amino acids, phenylpropanoids, and organic acids. Thereinto, combined treatment of Bacillus consortium and quercetin (1.0 mM) ameliorated the production of different metabolites in tomato plants. These findings prove the imperative use of Bacillus consortium and quercetin as an effective and sustainable remedy to manage Fusarium wilt disease of tomato plants and to promote the growth of tomato plants under pathogen stress conditions.

Land use/land cover (LULC) changes have a substantial influence on ecosystem services. The objective of this study is to estimate LULC dynamics induced ecosystem service values (ESV) changes in Western Ethiopia. Data were acquired from Landsat images of the area for four periods (1990-2020), and 221 sample households. The areas of LULC classes and the improved ESV coefficients of Costanza et al (1997) were used estimate ESV changes in 1990-2020. Forest provides diverse provisions, regulatory, supportive and cultural services. Analysis of the Landsat images showed that forest, farmland, settlement, water body and bare-land were the major LULC classes in the study area. While forest ESV had accounted 46.1% (US$ 4.95 million) of the ESV of Wayu-Tuka district in 1990, farmland ESV constituted the largest share (63.3%, US$ 5.21 million) of the ESV of the area after 30 years (2020). The ESV of forest and bare-land showed decreasing trends in three decades (1990-2020) but the farmland service value revealed an increasing trend in the same periods. Forest ecosystem exhibited the largest service value loss (US$ 3.91 million) in 1990-2020; whereas, the service value gain of farmland was only US$ 2.2 million although farmland was responsible for the conversion of the largest area size (9,766.5 ha) from other land covers in 30 years. LULC change induced net ESV loss of the district in three decades (1990-2020) was 23.4% (US$ 2.51 million). Land conversion due to expansion of farmland (by 9,766.5 ha) and settlement (by 4,061.3 ha) was the main cause for the LULC dynamics and the significant ESV loss in 1990-2020. Thus, the government and local people should cooperate so as to curb the steady degradation of forest and its ecosystem services in Wayu-Tuka district, Western Ethiopia.

A switchable and tunable terahertz (THz) metamaterial based on photosensitive silicon and Vanadium dioxide (VO2) was proposed. By using finite-difference time-domain (FDTD) method, the transmission and reflective properties of the metamaterial were investigated theoretically. The results imply that, the metamaterial can realize a dual electromagnetically induced transparency (EIT) or two narrow-band absorption depending on the temperature of the VO2. Additionally, the magnitude of the EIT and two narrow-band absorption can be tuned by varying the conductivity of photosensitive silicon (PSi) via pumping light. Correspondingly, the slow light effect accompanying the EIT can also be adjusted.

The plant immunity system is more and more revisited and new elements and roles are attributed to participate in the response to biotic stress. New terminology is also applied trying to identify different players in the whole scenario of immunity: Phytocytokines are one of those elements that are gaining more attention due the characteristics of processing and perception, and showing they are part of a big family of compounds that can amplify the immune response. This review aims to highlight the last findings about the role of phytocytokines in the whole immune response on biotic stress, including basal and adaptive immunity, and to expose the complexity in their action in plant perception and signaling events.

This study presents the developments regarding the time-domain-induced polarisation method, as a supporting tool for resistivity soundings during investigations of coastal detrital aquifers that are salinised by marine intrusion. The interpretation of resistivity measurements in such aquifers, which have variable hydrochemistry and lithology, involves uncertainties owing to the presence of low-resistivity lithologies, such as clays. To reduce these uncertainties, the use of other geophysical parameters is necessary; hence, this study focuses on induced polarisation, since it can be measured simultaneously with resistivity. In detail, we propose the determination of induced polarisation using 1D techniques, while developing a different algorithm for processing the induced polarisation data. The aim is to extend the results of this phenomenon, using instead of chargeability, the concepts of polarisability and decay time, which are extracted from the decay curve, given that they represent more intrinsic properties of the various analysed subsurface media. We present results obtained by applying this methodology to a Quaternary aquifer of the Costa del Sol in the SE Iberian Peninsula (in the province of Almería) during two different campaigns, one before and one after winter (i.e., in October and February, respectively). The results reveal the position of the saline front during each campaign, while reflecting the seasonal movement of the marine intrusion.

This paper develops the study of the effect of powerful ultrasound on the laser breakdown of liquids and a comparative study of the possibilities of acoustic and optical diagnostics of breakdown. The method of laser-induced breakdown spectroscopy (LIBS) for elemental analysis of liquids, along with high efficiency, continues to be less sensitive compared to traditional chemical methods. The paper develops a method of using additional ultrasound irradiation of the laser breakdown area in order to increase the efficiency of LIBS. Using the developed technique, spectral lines of chemical elements such as potassium, manganese, sodium, calcium, etc. were obtained for the first time depending on the frequency and power of ultrasound. It is shown that a sharp increase in the intensity of spectral lines of elements in water during laser breakdown is observed in the field of high-power ultrasound. It indicates an increase in the sensitivity of the combined method of ultrasonic LIBS. Along with the optical spectrum, the spectral and energy characteristics of acoustic emission were studied. An automated complex for hydrophysical and spectral studies is described, which was tested in the Sea of Japan during the voyage No. 81 of the research vessel RV "Professor Gagarinsky" in August 2022.

We have developed an unsteady and non-linear wind synopsis simulator called RIAM-COMPACT (Research Institute for Applied Mechanics, Kyushu University, COMputational Prediction of Airflow over Complex Terrain) in order to simulate the airflow on a microscale, i.e., a few tens of km or less. In RIAM-COMPACT, the large-eddy simulation (LES) has been adopted for turbulence modeling. LES is a technique in which the structures of relatively large eddies are directly simulated and smaller eddies are modeled using a sub-grid scale model. In the present study, we have conducted the numerical wind diagnoses for Taikoyama Wind Farm nacelle separation accident in Japan. The simulation results suggest that all six wind turbines at the Taikoyama Wind Farm are subject to significant influence from separated flow (terrain-induced turbulence) which is generated due to the topographic irregularities in the vicinity of the wind turbines. A proposal has been also made on reconstruction of the wind farm.

Sepsis-associated encephalopathy (SAE) is a common brain dysfunction following sepsis that often results in severe cognitive and neurological sequelae and increases the mortality rate in patients with sepsis. Microglia are resident macrophages in the brain that play essential roles in the pathological and physiological processes of SAE. Depending on the nature of the stimulus, microglia can adopt two polarization states (M1/M2), which correspond to altered microglial morphology, gene expression, and function. Therefore, we systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE. We demonstrated that microglia are closely related to occurrence and development of SAE and concomitant cognitive impairement. Finally, we outlined some potential therapeutic approaches that can prime microglia and neuroinflammation towards the beneficial restorative microglial phenotype in SAE.

Background: Low T3 syndrome occurs frequently in patients with sepsis. Type 3 deiodinase (Dio3) is present in immune cells but there is no description of its presence in this patients. Here we aimed to determine the prognostic impact of thyroid hormones levels (TH) measured on ICU admission on mortality and on evolution to chronic critical illness (CCI) and the presence of D3 in white cells. Methods: Prospective cohort study with a follow-up for 28 days or deceased. Results: Low T3 levels at admission were present in 86.5% of the patients. Dio3 was 55% induced in immune cells. The cut-off value of 60 pg/mL for T3 displayed a sensitivity and specificity of 81% and 64% for predicting death, odds ratio of 4.89. Lower T3 yielded an area under the receiver operating characteristic curve of 0.76 and 0.75 for mortality and evolution to CCI, respectively, thus displaying better performance than commonly used prognostic scores. Conclusions: We advance in the pathophysiology of low T3 showing induced D3 in immune cells during sepsis. Low T3 levels independently predicted a progression to CCI and mortality within 28 days in sepsis and septic shock.

The presented research faces the problem of early detection of sepsis for patients in the Intensive Care Unit. The PhysioNet/Computing in Cardiology Challenge 2019 facilitated the development of automated, open-source algorithms for the early detection of sepsis from clinical data. A labeled clinical records dataset for training and verification of the algorithms was provided by the challenge organizers. However, a relatively small number of records with sepsis, supported by Sepsis-3 clinical criteria, led to highly unbalanced dataset (only 2% records with sepsis label). A high number of unbalanced data records is a great challenge for machine learning model training and is not suitable for training classical classifiers. To address these issues, a number of various models were investigated. A solution including feature selection and data balancing techniques was proposed in this paper. In addition, several performance metrics were investigated. Results show, that for successful prediction, a particular model having few or more predictors based on the length of stay in the Intensive Care Unit should be applied.

Immune response stimulation may be an adjuvant to antimicrobial treatment. Here, we evaluated the impact of immune response modification by lysophosphatidylcholine (LPC) combined with imipenem or ceftazidime in murine models of peritoneal sepsis (PS) and pneumonia by Pseudomonas aeruginosa. Imipenem and ceftazidime-susceptible strain (Pa39), and imipenem and ceftazidime-resistant strain (Pa238) were used. Ceftazidime pharmacokinetic and pharmacodynamic parameters were determined. Therapeutic efficacy, and TNF-α and IL-10 levels were determined in murine models of PS and pneumonia by Pa39 and Pa238 treated with LPC, imipenem or ceftazidime, alone or in combination. In PS model, LPC+ceftazidime reduced spleen and lungs Pa238 concentrations (-3.45 and -3.56 log10 CFU/g; P<0.05) than ceftazidime monotherapy, while LPC+imipenem maintained the imipenem efficacy (-1.66 and -1.45 log10 CFU/g; P>0.05). In pneumonia model, LPC+ceftazidime or LPC+imipenem reduced lungs Pa238 concentrations (-2.37 log10 CFU/g, P=0.1, or -1.35 log10 CFU/g, P=0.75). For Pa39 no statistically significant difference has been observed in PS and pneumonia models between combined therapy and monotherapy. Moreover, LPC+imipenem and LPC+ceftazidime decreased and increased significantly TNF-α and IL-10 levels, respectively, in comparison with untreated controls and monotherapies. These results demonstrate the impact of immune response modification by LPC plus antibiotics on the prognosis of infections by ceftazidime-resistant P. aeruginosa.

In January and February 2001, El Salvador was hit by two strong earthquakes that triggered thousands of landslides, causing 1,259 fatalities and extensive damage. The analysis of aerial and SPOT-4 satellite images taken a few days after the events allowed us to map 6,491 coesismic landslides, which occurred in 14 study areas extending for about 400 km2. Four different Multivariate Adaptive Regression Splines (MARS) models were produced by using different covariate sets and landslide inventories, the latter containing the slope failures triggered by an extreme rainfall event of November 2009 and those induced by the earthquakes of 2001. Moreover, two validation scenarios were employed, including the 25% and 95% of the mapped landslides, respectively. The results of our experiment revealed that: (i) MARS algorithm provides reliable predictions of coesismic landslides; (ii) models calibrated with rainfall-induced landslides predict with acceptable accuracy landslides caused by deep earthquakes and distributed over vast areas; (iii) the best accuracy is achieved by models trained with both preparatory and trigger variables; (iv) a small portion of the landslides produced by an earthquake can be used to calibrate MARS predictive models that help to identify slopes where yet unreported landslides may have occurred.

Drug-induced liver disease represents one of the main problems in the therapeutic field. As with most pathologies, also in this case various risk factors can be recognised, such as age, sex, but also the gut microbiota. Therefore all drugs on the market can, in fact, cause hepatotoxicity of varying degrees. Drugs used in the treatment of IBD can also cause these adverse effects and even lead to DILI. In this review, the various classes of drugs used in the treatment of IBD were taken into consideration and the various adverse effects on the liver were illustrated. In particular, a major role has emerged regarding hepatotoxicity of immunosuppressants. Biological drugs, however, seem to be responsible for these complications to a much lesser extent.

Within the spectra of lanthanide atoms quite often overlapping spectral lines (blends) are observed. On the example of complicated blend situations within Pr I and La I it is shown that in such cases a combination of optogalvanic and laser-induced fluorescence detection is necessary to find all transitions contributing to the observed spectral signature.

Peptidylarginine deiminases (PADs) have an important role in the pathogenesis of generating citrullinated proteins which is one type of protein posttranslation modifications (PTMs). Additionally, peptidylarginine deiminases 4 (PAD4) is a component of neutrophil extracellular traps (NET) that leads to autoimmune disease during NETosis. Our aim was to check the PAD4 enzyme expression at level of gene and protein expression in streptozotocin (STZ) induced diabetic rat pancreas and checking the link between PAD4 and inflammatory cytokines. Wistar rats were divided into two groups: control group and diabetic STZ group. STZ was administered by intraperitoneally (60 mg/kg/ body weight). Rats were caged for six weeks and then terminated. Pancreatic tissue was harvested for measurement of PAD4 protein expression, PAD4 mRNA, citrulli-nated histone-3 protein (CITH3), cytokines and Ca2+ content. All measurements in diabetic rats were significantly in-creased compared to non-diabetic rats (p

Tongue mobility is an obstructive sleep apnoea (OSA) marker and myofunctional therapy (MFT) target. For this reason, all patients with sleep-disordered breathing should require a combined functional assessment from an ear, nose, and throat (ENT) specialist and a phonoaudiologist to confirm or rule out the presence of tongue-tie. To our knowledge, this is the first case of a 13-year-old girl diagnosed with severe OSA and a significant decrease of 94% in her apnoea index (AI), requiring frenotomy with immediate postoperative change in the tongue position. A drug-induced sleep en-doscopy (DISE) was performed before and immediately post-frenotomy, and the anatomical changes provoked by this surgery during sleep were confirmed for the first time.

Induced pluripotent stem cells (iPSC) are derived from reprogrammed adult somatic cells. These adult cells are manipulated in vitro to express genes and factors essential for acquiring and maintaining embryonic stem cell (ESC) properties. This technology is widely applied in many fields, and there has been much attention to developing iPSC-based disease models to validate drug discovery platforms and study pathophysiological molecular processes underlying disease onset. Especially in neurological diseases, there is a great need for iPSC-based technological research, as these cells can be obtained from each patient and carry the individual’s bulk of genetic mutations and properties. Moreover, iPSC can differentiate into multiple cell types. These are essential characteristics since the study of neurological diseases is affected by limited access to injured sites, in vitro models composed of various cell types, the complexity of reproducing the brain’s anatomy, ethical issues, and the fact that post-mortem cell culture is challenging. Neurodegenerative diseases enormously impact global health due to their high incidence, symptoms severity, and usually lack of effective therapies. Recently, analyses using disease-specific iPSC-based models confirmed their efficacy for testing multiple drugs. This review summarizes the advances in iPSC technology used in disease modeling and drug testing with a primary focus on neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases.

Idiosyncratic drug induced liver injury (DILI) is an unpredictable reaction of exposed individual on a certain drug, and the drug-induced autoimmune hepatitis (DIAIH) presents a DILI phenotype that mimics idiopathic autoimmune hepatitis (AIH) when considering the clinical, biochemical, serological and histological parameters. We present a case of a 48-year-old male that was hospitalized due to severe hepatocellular liver injury two months after the self-treatment with the muscle-building dietary supplement based on arginine-alpha-ketoglutarate, L-citrulline, L tyrosine, creatine malate and beet extract. His immunology panel was positive with increased IgG levels, and the radiologic methods showed no signs of chronic liver disease. He underwent corticosteroid treatment with adequate response. After the therapy withdrawal, a clinical relapse occurred. Seven months after the initial presentation liver MR suggested the initial cirrhotic changes of the right liver lobe. Liver biopsy revealed abundant lymphoplasmacytic infiltrate with piecemeal necrosis and grade 2 fibrosis. He responded well on the corticosteroid treatment again, and was further treated with low dose prednisone without additional relapses. Several years later, further management confirmed presence of liver cirrhosis with no histological or biochemical signs of the disease activity. DIAIH is a DILI phenotype difficult to distinguish from idiopathic AIH despite a wide armamentarium of diagnostic methods. Regular patient monitoring and clinical open-mindedness with the adjustment of therapeutic approaches according to the disease course are more important than strict labelling of the disease.

Background: Pteropodine (PT) is a component of some plants with potentially useful pharmaco-logical activities for humans. This compound has biomedical properties related to the modulation of the immune system, nervous system, and inflammatory processes. This study addresses the an-ti-inflammatory and antioxidant capacity of pteropodin in a murine model of arthritis and induced edema of the mouse ear. Methods: To evaluate the anti-inflammatory activity, we used the reversed passive Arthus reaction (RPAR), which includes the rat paw edema test, the rat pleurisy test, and a mouse ear edema model. The antioxidant effect was evaluated by determining the myeloperoxidase enzyme activity. Results: PT showed an anti-inflammatory effect in the different specific and non-specific tests. We found a 52 to 74% of inhibitory effect of PT in the rat paw edema test, 52% of reduction of the pleural exudate volume, and low neutrophil count (28%), when compared to the control group. We also found a 81% of inflammatory inhibition of the ear edema, and a significant myeloperoxidase enzyme inhibition by the three doses of PT. Conclusions: PT exerted a potent an-ti-inflammatory effect in the acute inflammation model in rodents.

The soil-borne pathogens, particularly Fusarium oxysporum f. sp. niveum (FON) and southern root-knot nematode (RKN, Meloidogyne incognita) are the major threat to watermelon production in the south-eastern United States. The role of soil micronutrients on induced resistance (IR) to plant diseases is well-documented in soil-based mediums. However, soil-based mediums limit the determination of the role(s) of individual micronutrients in IR. In this manuscript, we utilized hydroponics to assess the effect of controlled application of micronutrient, including iron (Fe), manganese (Mn), and zinc (Zn) on the expression of some IR genes (PR1, PR5, and NPR1 from salicylic acid (SA) pathway, and VSP, PDF, and LOX genes from jasmonic acid (JA) pathway) in watermelon seedlings upon inoculation with either FON or RKN or both. Plants were treated with higher (3X) or lower (0.5X) concentrations of micronutrients in Steiner solution (X= standard dose of micronutrient) for 7 days in a hydroponics system under greenhouse conditions. A subset of micronutrient-treated plants was inoculated (on the 8th day of micronutrient application) with FON and RKN (single and mixed). The expression of the IR genes in treated and control samples were evaluated using qRT-PCR. Although, significant phenotypic differences were not observed with respect to the severity of wilt symptoms or RKN galling with any of the micro-nutrient treatments within the 30 day-experimental-period, differences in the induction of IR genes were observed. However, the level of gene expression varied with sampling period, type and concentration of micro-nutrients ap-plied, and pathogen-inoculation. In the absence of pathogens, no significant changes were observed in the expression level of IR genes on 7th day of micronutrient treatment. However, pathogen inoculation affected the expression levels of the IR genes at 3-day post-inoculation. In FON inoculated plants, PDF was upregulated in high Fe treatment, whereas in RKN inoculated plants, low Mn treatment resulted in up-regulation of VSP. In the case of mixed inoculation with FON and RKN, the plants with low Zn treatment resulted in the upregulation of PR1. These observations suggest that the type and concentration of micronutrients in watermelon may potentially induce systemic resistance against FON and RKN through SA and JA pathways.

MiRNAs are 20-22 nucleotide long single-stranded non-coding RNA sequences, which can regulate post transcriptional activity of mRNA by binding with it at 3’UTR region (untranslated region). Thus deregulation of miRNA expression is responsible for dysregulating mRNA function which contributes in developing various diseases as well as cancerous phenotypes. Alteration of single nucleotide in miRNA sequence is one of the reasons behind deregulation of miRNA expression. The most frequent carcinoma in current day is breast cancer which causes a high mortality among women around the world as well as India. Despite of the advancement of diagnostic tools, strategies and treatment, the cases of breast cancer is increasing every year. There are plenty of biomarkers like ER, PR, Her2, Ki-67, etc available which are frequently used in diagnosis and treatment of breast cancer. After the discovery of MiRNA in 1993 in Caenorhabiditis elegans, it is attracting all the limelight in diagnosis and treatment of different carcinomas as well as breast cancer. In this review we will discuss on involvement of different types of MiRNAs and miR SNPs in breast cancer occurrence and susceptibility in a detailed manner.

The color changes corresponding to chromophore structures in lignin caused by exposure of Eucalyptus（Eucalyptus grandis and E. urophylla）to heat were investigated. Eucalyptus wood samples were heated in saturated steam atmospheres for 10 h at 110℃, 130℃, and 150℃. The lignin was isolated before and after heat treatment. The physicochemical properties of the lignin and changes in chromophore structures during heat treatment was evaluated through wet chemical analysis, FTIR, UV-Vis, GPC, XPSand 13C-NMR. The color of the wood became darker and redder with the increase in pressure and temperature. Depolymerization and dehydration reactions occurred via demethoxylation with heat treatment in saturated steam at 110℃ or 130℃. Lignin condensed to form insoluble compounds after heat treatment in saturated steam at 150℃. G units increased and S units decreased through demethylation during heat treatment, as revealed by FTIR and 13C-NMR analysis.

In the present study, field observation wind data from the time of the wind turbine blade damage accident on Shiratakiyama Wind Farm were analyzed in detail. In parallel, high-resolution LES turbulence simulations were performed in order to examine the model’s ability to numerically reproduce terrain-induced turbulence. The comparison of the observed and simulated time series (1 second average values) from a 10 minute period from the time of the accident led to the conclusion that the settings of the horizontal grid resolution and time increment are important to numerically reproduce the terrain-induced turbulence that caused the wind turbine blade damage accident on Shiratakiyama Wind Farm. A spectral analysis of the same set of observed and simulated data revealed that the simulated data reproduced the energy cascade of the actual terrain-induced turbulence well.

At the Atsumi Wind Farm in Aichi Prefecture, Japan, damage to wind turbines occurred frequently due to terrain-induced turbulence. In the present study, numerical analyses of terrain-induced turbulence were conducted by reproducing the topography in the vicinity of the wind turbine sites in high resolution and using RIAM-COMPACT natural terrain version, which is based on large eddy simulation (LES). The results of the diagnoses indicated that, in the case of south-easterly wind, terrain-induced turbulence is generated at a small terrain feature located upstream of Wind Turbine (WT) #2, which serves as the origin of the turbulence. At the Atsumi Wind Farm, a combination of the series of wind diagnoses and on-site operation experience led to a decision to adopt an "automatic shutdown program" for WTs #1 and #2. Here, "automatic shutdown program" refers to the automatic suspension of wind turbine operation upon the wind speed and direction meeting the conditions associated with significant effects of terrain-induced turbulence at a wind turbine site. The adoption of the "automatic shutdown program" has successfully resulted in a large reduction in the number of occurrences of wind turbine damage, thus, creating major positive economic effects. 1) a reduction in the repair costs by 9.322 million yen per year per wind turbine, 2) an increase in the availability factor by 8.05%, and 3) an increase in the capacity factor by 1.7%.

We use earthquake ground motion modelling via Ground Motion Prediction Equations (GMPEs) and numerical simulation of seismic waves to consider the effects of site amplification and basin resonance in Jakarta, the capital city of Indonesia. While spectral accelerations at short periods are sensitive to near-surface conditions (i.e., Vs30), our results suggest that, for basins as deep as Jakarta’s, available GMPEs cannot be relied upon to accurately estimate the effect of basin depth on ground motions at long periods (>1 s). Amplitudes at such long periods are influenced by entrapment of seismic waves in the basin, resulting in longer duration of strong ground motion, and interference between incoming and reflected waves as well as focusing at basin edges may amplify seismic waves. In order to simulate such phenomena in detail, a basin model derived from a previous study is used as a computational domain for deterministic earthquake scenario modeling in a 2-dimensional cross-section. A M_w 9.0 megathrust, a M_w 6.5 crustal thrust and a M_w 7.0 instraslab earthquake are chosen as scenario events that pose credible threats to Jakarta, and the interactions with the basin of seismic waves generated by these events were simulated. The highest PGV amplifications are recorded at sites near the middle of the basin and near its southern edge, with maximum amplifications of PGV in the horizontal component of 200% for the crustal, 600% for the megathrust and 335% for the deep intraslab earthquake scenario, respectively. We find that the levels of ground motion response spectral acceleration fall below those of the 2012 Indonesian building Codes's design response spectrum for short periods (< 1 s), but closely approach or may even exceed these levels for longer periods.

A metastable β-Ti alloy, Ti–10V–3Fe–3Al (wt.%), was subjected to thermos-mechanical processing including the compression test at 725°C, which is below the β transus temperature (780°C), and at strain rate of 10-3s-1. The presence of phases was determined using transmission electron microscopy and X-ray diffraction. Although the dynamic recovery took place together with slip, both deformation-induced α˝ martensite and ω were detected as other operating mechanisms for the first time in metastable-β Ti alloys deformed in α+β region. The volume fraction of stress-induced α˝ was higher than that of the same alloy deformed at room temperature due to higher strain applied. Stress-induced twinning was not operational, which could be related to the priority of slip mechanism at high temperature resulted from thermally-assisted nucleation and lateral migration of kink-pairs.

.Bacground: Sepsis remains a major health challenge worldwide, characterized by a dysre-gulated host response to infection, leading to high mortality and morbidity in intensive care units (ICUs). The Fibrosis 4 (FIB-4) index, originally developed to assess liver fibrosis in hepatitis C patients, has recently been explored for its potential prognostic value in sepsis patients. Method: This study retrospectively analyzed 309 sepsis patients admitted to the Internal Me-dicine and Anaesthesia ICUs between December 12, 2021, and December 15, 2023, to inves-tigate the relationship between FIB-4 levels, Acute Physiology and Chronic Health Evaluation (APACHE), and Sequential Organ Failure Assessment (SOFA) and clinical outcomes. Results: The study found that higher FIB-4 measurements were statistically significantly asso-ciated with increased 28-day mortality, with a cut-off value of 4.9 providing a sensitivity of 54.92% and specificity of 74.25%. Logistic regression analysis indicated that elevated Conclusion:FIB-4 levels were a significant predictor of early mortality, suggesting that the FIB-4 index could serve as a valuable prognostic tool in assessing the severity and prognosis of sepsis patients.