Objectives: Evaluate hand-held echocardiography (HHE) performed and interpreted by trained Advanced Practice Providers (APPs) on hospitalized CHF patients for image quality and interpretation, by comparing against expert echocardiographer and SE findings. Background: Congestive heart failure (CHF) is associated with increased hospital admissions and mortality. While standard echocardiogram (SE) is the gold standard for cardiac assessment, it is not readily available. Hospitalized CHF patients require rapid assessment for expedited treatment. Methods: Over 6 months, five trained APPs performed HHE on hospitalized CHF patients and interpreted: a) Left ventricular (LV) size, b) LV ejection fraction (LVEF), and c) right atrial pressure (RAP). The study echocardiographer reviewed and blindly interpreted HHE images and compared with APPs and SE findings. Kappa-statistics determined the degree of agreement between APPs and study echocardiographer interpretation of HHE images and SE. Results: 80 CHF patients [age 73±14 years, 58% males; LVEF (by SE) 45±19%; 36.3% body mass indexes ≥30 kg/m2] were enrolled. HHE interpretation by APPs had good agreement for LVEF (kappa 0.79) with study echocardiographer and SE (kappa 0.74), and good agreement for RAP (kappa 0.67) with study echocardiographer. Correlation between absolute LVEF interpretation by study echocardiographer on HHE and SE was r=0.88 (p<0.0001). Conclusions: Trained APPs obtained diagnostic-quality HHE images and interpreted LV function and RAP in CHF patients, with good agreement with the study echocardiographer. LVEF by HHE correlated with LVEF by SE. Our study suggests trained APPs can use HHE to evaluate LVEF and RAP in CHF patients leading to expedited and optimized treatment.

Psilocybin-containing mushrooms, commonly known as magic mushrooms have antidepressant effect, however, their safety in cardiovascular diseases such as heart failure is not fully known and needs to be investigated. Cardiac hypertrophy is an independent risk factor for heart failure morbidity and mortality. Angiotensin II (Ang-II) plays a major role in the pathogenesis of cardiac hypertrophy. We investigated the cardiovascular safety of extracts of Panaeolus cyanescens, Psilocybe natalensis, Psilocybe cubensis, and Psilocybe cubensis leucistic A+ strain mushrooms, well-known psilocybin-containing mushrooms in the Panaeolus and Psilocybe genus on Ang II-induced hypertrophy oxidative stress. The four mushrooms were grown, dried and extracted with 70% ethanol, cold and hot water. Extracts were tested for cytotoxicity on H9C2 cardiomyoblast cells. The cardiomyocytes were induced with (10 µM) AngII and treated with the three extracts of the four mushrooms over 48 hours. Control cells were serum starved but neither AngII induced nor treated while AngII cells were serum starved and stimulated with AngII but not treated. Losartan, an inhibitor of AngII type 1 receptor was used as positive control. Effects of the extracts on actin-filament labelling and cell surface area, mitochondrial activity, reactive oxygen species (ROS) and atrial natriuretic peptide levels were determined. Stimulation with AngII lowered cell viability, increased the cell width measurements and intracellular ROS levels significantly compared to control cells. The results indicated that the ethanol and water extracts of the four psilocybin mushrooms did not exacerbate the angiotensin II-induced hypertrophy conditions, but the extracts had cardio-protective activity against angiotensin II-induced oxidative stress. The phytochemical analysis of the extracts confirmed detections of known compounds with antioxidant and anti-inflammatory effects in the water and ethanol extracts of these four psilocybin mushrooms.

The construction of a house with a stage structure is the uniqueness of Banjarmasin's swampland. Particularly, foundations for swampy terrain necessitate special handling. Building material defects and the basic inability to modify the use and design of wood pillar foundations are the main causes of house building problems. The very limited capacity of a wooden pillar foundation makes house buildings collapse frequently. The aim of the study is to determine the weaknesses of the wooden pillar foundations by examining the indications of damage to the house structure. Field observation investigations, including housing and individual object observations, will be carried out at multiple construction sites in Banjarmasin (Indonesia) as part of this study. The way the data is presented is descriptive. A wooden pillar foundation, which is a frequently used foundation, has a limited load bearing capacity. Because that, there has been no related research that addresses the issue of how this foundation damage. The aim of the study is to determine the early signs of swamp building collapse in the wooden pillar foundations weaknesses by examining the indications of damage to the house structure. The weak construction of a wooden pillar foundation explains some indications of house building damage, such as broken wooden pillars and floor settlement. The existence of evidence that there is a broken 'sunduk’ element is one of the causes of damage to this foundation

Lophomonas are flagellated protozoa which have been increasingly associated with upper and lower airway infection in humans. The prevalence and characterization of this disease in the critically ill remains poorly understood. We present a series of eleven ICU patients with confirmed Lophomonas spp. identification in respiratory samples.

Abstract The heart serves as the pivotal organ generating rhythmic contractions allowing blood ejection from the ventricles and its circulation in the cardiovascular system. Contractions of the heart requires oxygen and energy consumption and removal of metabolic factors from cardiac myocytes. The mechanical performance of the cardiac muscle and production of the vasoactive factors are significantly affected in cardiovascular and metabolic diseases, especially in the heart failure, hypertension and diabetes mellitus. The processes affecting coronary blood flow and cardiac contractility in these diseases are not fully recognized. The present review draws attention to specific role of angiotensin peptides, vasopressin and insulin in the regulation of the coronary blood flow and cardiac contractions. There is evidence for intracardiac production of some of these compounds and their importance in the regulation of the cardiac tissue oxygenation, energy production and metabolism, and generation of other cardiovascular compounds, such as nitric oxide, bradykinin and endothelin. Presence of receptors for angiotensin II, angiotensin-(1-7) and insulin in the coronary vessels and cardiomyocyes sets up conditions for interaction of these factors at the signaling level. Coronary vessels and cardiac muscle possess AT1 and AT2 receptors, angiotensin-1-7 receptor, vasopressin V1 receptor, and insulin receptor substrates. Expression of these receptors and responsiveness to angiotensins, vasopressin and insulin are altered during heart failure, hypertension, obesity and diabetes mellitus, especially when these diseases occur simultaneously. The survey of the literature presented in the review provides evidence for the belief that very individualized treatment, including interactions of angiotensins and vasopressin with insulin, should be selected for patients suffering simultaneously for cardiovascular and metabolic diseases.

The purpose of this study is to investigate the failure mechanism and preventive strengthening methods of prefabricated full length small box girder (PSBG) under car explosion. After damage analysis during blast loads using the commercial software Autodyn, three strengthening methods are presented to improve the blast mitigation performance. The results show that the failure modes and bearing capacity are significantly different with various strengthening measures. Adhering U-shaped steel plate can effectively enhance the shear performance of PSBG under blast loads. Strengthening the bottom of the upper flange of box girder with steel plate can effectively mitigate the local bending failure, and enhance the overall flexural capacity during car explosion.

Heart failure (HF) management in type 1 diabetes (T1D) is particularly challenging due to its increased prevalence and the associated risks of hospitalization and mortality, driven by diabetic cardiomyopathy. Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) offer a promising avenue for treating HF, specifically the preserved ejection fraction variant most common in T1D, but their utility is hampered by the risk of euglycemic diabetic ketoacidosis (DKA). This review investigates the potential of SGLT2-i in T1D HF management, alongside the emergent Continuous Ketone Monitoring (CKM) technology as a means to mitigate DKA risk, through a comprehensive analysis of clinical trials, observational studies, and reviews. The evidence suggests SGLT2-i significantly reduce HF hospitalization and enhance cardiovascular outcomes. However, their application in T1D patients remains limited due to DKA concerns. CKM technology emerges as a crucial tool in this context, offering real-time monitoring of ketone levels, which enables the safe incorporation of SGLT2-i into treatment regimes by allowing for early detection and intervention in the development of ketosis. The synergy between SGLT2-i and CKM has the potential to revolutionize HF treatment in T1D, promising improved patient safety, quality of life, and reduced HF-related morbidity and mortality. Future research should aim at clinical trials directly assessing this integrated approach, potentially guiding new management protocols for HF in T1D.

There is a bidirectional relationship between the heart and the gut. Gut microbiome is an excellent gut-homeostasis keeper since controls the growth of potentially harmful bacteria and protects the microbiota environment. There is evidence suggesting that diet rich in fatty acid can be metabolized and converted by gut microbiome and hepatic enzymes to trimethyl-amine N-oxide (TMAO) a product that is associated with atherogenesis, platelet dysfunction, thrombotic events, coronary artery disease, stroke, heart failure and ultimately death. Heart failure, by inducing gut ischemia and congestion and consequently gut barrier dysfunction promote an intestinal leak of microbes or even of their products, facilitating their entrance into the circulation and thus stimulating the low-grade inflammation and hence the immune response. Drugs used for heart failure may alter the gut microbiome, and conversely gut microbiome may modify the pharmacokinetic properties of the drugs. Modification of lifestyle based mainly on exercise and Mediterranean diet along with the use of pre- or probiotics may be beneficial to some extent for the gut microbiome environment. The potential role of gut microbiome in heart failure development and outcomes is a fruitful area of future research.

Heart failure with preserved ejection fraction (HFpEF) is a leading form of human cardiovascular disease and commonly associated with systemic hypertension. Unique evolved adaptations in giraffe myocardia may be a natural animal model of resistance to HFpEF. In humans, pressure-overload induced left ventricular thickening (PLVT) impairs diastolic relaxation, elevates left atrial pressures and may progress to heart failure with symptoms including exercise intolerance. In healthy giraffe, the left ventricle thickens as developmental neck lengthening widens the vertical distance between the heart and head increasing pressures needed to maintain constant brain perfusion. Yet, diastolic relaxation and exercise capacity are unimpaired, a critical adaptation for prey species such as giraffe. The proximate mechanisms underlying this unique cardiovascular physiology are not yet characterized. Developmental PLVT in giraffe emerges as a species-specific evolved adaptation which offers a roadmap for identifying innovations in therapeutic and prevention strategies for HFpEF.

Diabetes mellitus is associated with cardiovascular, ophthalmic, and renal comorbidities. Among these, diabetic cardiomyopathy (DCM) causes the most severe symptoms and is considered to be a major health problem worldwide. Exercise is widely known as an effective strategy for the prevention and treatment of many chronic diseases. Importantly, the onset of complications arising from diabetes can be delayed or even prevented by exercise. Regular exercise is reported to have positive effects on diabetes mellitus and the development of DCM. The protective effects of exercise include the prevention of cardiac apoptosis, fibrosis, oxidative stress, and microvascular diseases, as well as improvement in cardiac mitochondrial function, and calcium regulation. The present review summarizes the recent findings to describe the potential mechanisms by which exercise may prevent DCM and heart failure.

Introduction In sacubitril-valsartan (sacub/v), the effects of an angiotensin II receptor blocker (ARB) exerted by valsartan are strengthened by the addition of sacubitril, an inhibitor of neutral endopeptidases. PARADIGM - HF study proved this association to be superior to enalapril in reducing both all-cause death and cardiovascular mortality, as well as heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction( HFREF) belonging to NYHA class II-IV. To test whether even in our experience sacub/v is associated with favorable outcomes concerning mortality and morbidity, an outpatient small population of HFREF patients was retrospectively studied, of whom one third was treated with sacub/v instead of conventional therapy with ACE -inhibitors or ARBs. Methods A retrospective cohort study was carried out to assess the effects of sacub/v in addition to beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients in NYHA classes II-III compared with conventional therapy (comprising ACE inhibitor or ARB added to beta-blocker plus a MRA) administered in a second group of HFREF patients with comparable clinical features retrospectively enrolled as controls. In the two groups, the therapeutic regimen was established in accordance with the preferences of the treating physician. Additionally, in both groups, evidence-based drug therapy was supplemented by the adjunct of a loop diuretic, usually furosemide, at variable doses. The primary outcomes of interest were all-cause death and HF hospitalizations. Safety outcomes were symptomatic hypotension, angioedema, hyperkalemia and worsening renal function. Results Mortality at six months was 6.8% in patients under therapy with sacub/v versus 34% in those treated with conventional therapy (odds ratio[OR] = 0.14; 95% CI: 0.04-0.49). Moreover, HF hospitalizations in the observation period considered were 4.5% in sacub/v group versus 59% in the conventional therapy group (OR = 0.03; 95% CI: 0.01–0.14). Safety outcomes included in our study (angioedema, hyperkalemia, hypotension and worsening renal function) showed a comparable profile in the two groups, with evidence of good tolerability of sacub/v , except for the side - effect " hypotension" (PAS < 100 mm Hg) , found in 15.9% of patients under sacub/v versus 5.7% reported in controls (OR = 3.14; 95% CI: 0.94–10.55). Conclusions In our experience, sacub/v has yielded a strong protection against both all-cause death and HF hospitalizations at six months , in the absence of significant noxious side effects. Nevertheless, considering the retrospective character of the study and the relatively exiguous sample size, further post marketing observational studies would be desirable . In particular, studies aiming at exploring safety of the new pharmacologic principle, namely mainly focusing on hypotension and angioedema, are warranted, in order to validate further this very efficacious molecule for therapy of chronic HF, especially stable HFREF in NYHA classes II-III.

The present study investigates the failure mechanisms of industrial fiber materials, using a custom designed fiber cutting performance test bench. The fracture morphologies of single PA6 fibers are examined by scanning electron microscopy. The analysis reveals that fiber cutting can be distinguished according to four distinct stages of fiber failure represented by shearing, cutting, brittle fracture, and tensile failure, which are the result of different mechanisms active during the processes of crack initiation, extension and fracture. The results of fractographic analysis are further verified by an analysis of the blade assembly speed with respect to time over the entire fracture failure process based on high-speed camera data. The results of fractographic analysis and blade assembly speed are fully consistent.

The aim of this paper is to at first evaluate the influence of three key parameters including weld current, weld time and electrode force on nugget diameter and tensile strength in resistance projection welding. Then, a 2-D axis-symmetric finite element model is developed to simulate the projection welding and predict the nugget diameter. Finally, the FEM results are compared to experimental data to verify the simulation model and simulated results. In the finite element model, the temperature-dependent material properties were taken into account.

A systematic review and meta-analysis were conducted to estimate the prevalence of chlamydiosis in small ruminants. The study included 133 publications that reported the presence of Chlamydia abortus in 109 and 74 studies in sheep and goats from 45 countries. The prevalence of chlamydiosis was estimated at global, regional, and national levels using meta-analyses of proportions. Meta-regression and cumulative meta-analyses were also performed. Globally, the prevalence of chlamydiosis in sheep and goats was estimated at 20.1% (95% CI: 17.8-22.4) and 14.4% (11.6-17.4), respectively. For sheep, chlamydiosis prevalence was heterogeneous at regional and national levels. South Asia had the highest prevalence (30.6%) and East Asia and Pacific the lowest (14.0%). Nationally, chlamydiosis was more prevalent in Romania, Hungary, and Germany (range 53.3-87.0%) compared to Costa Rica, Australia, and Zimbabwe (4.7-5.2%). Among goats, chlamydiosis prevalence was similar across regions (10.4-19.7%), but varied significantly among countries, 0.0% in Romania and Australia and 91.7% in Bosnia and Herzegovina. In both species, sample size, number of diagnostic techniques, and latitude were significant covariates. Prevalence varied widely in the first decades of publications before stabilizing. Our study found a high prevalence of chlamydiosis in small ruminants, with the pathogen being distributed globally but heterogeneously across countries.

Background: There is limited data on gender-based differences in atrial fibrillation (AF) treatment and prognosis. Our aim was to examine gender-related differences in medical attention in emergency department (ED) and follow-up (FU) among patients diagnosed with an AF episode and to determine whether there are gender-related differences in clinical characteristics, therapeutic strategies and long-term adverse events in this population. Methods: We performed a retrospective observational study of patients who presented to a tertiary hospital ER for AF from 2010-2015, with a minimum FU of one year. Data on medical attention received, mortality and other adverse outcomes were collected and analyzed. Results: Among the 2 013 patients selected, 1232 (60%) was female. Women were less likely than men to be evaluated by a cardiologist during the ED visit (11.5% vs. 16.6%, p=0.001) and were less likely to be admitted (5.9% vs. 9.5%, p<0.05). Electrical cardioversion was performed more frequently in men, both during the first episode (3.4% vs. 1.2%, p=0.001) and during FU (15.9% vs. 10.6%, p<0.001), in spite of a lower AF recurrence rate in women (9.9% vs 18.1%). During FU, women had more hospitalizations for heart failure (26.2% vs. 16.1%, p<0.001). Conclusions: In patients with AF, although no gender differences in mortality, there were significant differences in clinical outcomes, medical attention received, and therapeutic strategies. Women underwent fewer attempts at cardioversion, had a lower probability of being evaluated by cardiologists and showed a higher probability of hospitalization for heart failure. Being alert to these iniquities should facilitate to adopt measures to correct them.

Extracellular vesicles (EVs) are emerging mediators of intracellular and inter-organ communications in cardiovascular diseases (CVDs), especially in the pathogenesis of heart failure through the transference of EV-containing bioactive substances. microRNAs (miRNAs) are contained in EV cargo and are involved in the progression of heart failure. Over the past several years, a growing body of evidence has suggested that the biogenesis of miRNAs and EVs are tightly regulated, and the sorting of miRNAs into EVs is highly selective and tightly controlled. Extracellular miRNAs, in particular circulating EV-miRNAs, have shown promising potential as prognostic and diagnostic biomarkers for heart failure and as therapeutic targets. In this review, we summarize the latest progress concerning the role of EV-miRNAs in HF and their application in a therapeutic strategy development for heart failure.

Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remote organ damage after trauma remain obscure. HMGB1 and inflammatory mediators were analyzed in plasma from 54 combat casualties, collected on admission to a military hospital in Iraq, and at 8 and 24 hours after admission. Forty-five (83%) of these patients had traumatic brain injury (TBI). Nine healthy volunteers were enrolled as controls. HMGB1 plasma levels were significantly increased in the first 8 hours after admission, and were found to be associated with systemic inflammatory responses, injury severity score, and presence of TBI. These data provided the rationale for designing experiments in rats subjected to blast injury and hemorrhage, to explore the effect of HMGB1 inhibition by CX-01. Animals were cannulated, then recovered for 5-7 days before blast injury in a shock tube and volume-controlled hemorrhage. Blast injury and hemorrhage induced an early increase in HMGB1 plasma levels that coincided with severity of tissue damage and mortality. CX-01 inhibited systemic HMGB1 release, decreased local and systemic inflammatory responses, significantly reduced tissue and organ damage, and tended to increase survival. These data suggest that CX-01 has potential as an adjuvant treatment for traumatic hemorrhage.

This case report presents a critical clinical scenario involving a 55-year-old patient who developed severe Plasmodium falciparum malaria with renal complications despite receiving doxycycline prophylaxis while travelling in a malaria-endemic region. The case emphasizes the potential failure of doxycycline prophylaxis and highlights the importance of considering malaria in patients with a history of travel to endemic areas, even if they have adhered to prophylactic treatment. The patient's clinical presentation included fever, extreme fatigue, and loss of consciousness, leading to hospitalization. Laboratory findings revealed severe anaemia, elevated liver enzymes, and impaired renal function, consistent with the criteria for severe malaria. The diagnosis was confirmed by the presence of Plasmodium falciparum parasites on blood smears. Due to limited access to parenteral antimalarial medications, the patient received oral artemether-lumefantrine, resulting in clinical improvement. Supportive care and dialysis played a vital role in the patient's recovery. This case report underscores the need for increased awareness of prophylaxis failure, the challenges of managing severe malaria in non-endemic countries, and the importance of timely and appropriate interventions to improve outcomes in severe malaria cases, particularly those with renal involvement. Further research is warranted to evaluate alternative preventive strategies in regions with drug-resistant malaria strains.

Introduction: Decompensated heart failure (HF) is a complex and debilitating syndrome, which constitutes a severe emergency condition with high morbidity and mortality. The kidneys play fundamental roles in the pathophysiology of HF and, in the context of decompensations, acute kidney injury (AKI) has a bilateral cause-and-effect relationship, which can significantly worsen prognosis. However, the interaction between AKI and decompensated HF is poorly understood. Objective: This study aimed to assess the occurrence of AKI in patients hospitalized due to decompensated HF and to analyze its prognostic impact during hospitalization. Methods: Prospective single-center observational study that included patients hospitalized due to decompensated HF in a tertiary-level teaching hospital, conducted between July 2017 and January 2020. Patients who developed AKI during hospitalization were compared with those who did not develop it, until hospital discharge or death. AKI was defined as a serum creatinine increase greater than or equal to 0.3 mg/dl in 48 hours, a 1.5-fold increase in baseline creatinine in seven days or urinary volume <0.5 ml/kg/h during six hours, according to the Acute Kidney Injury Network (AKIN) criteria. The endpoints analyzed were death, need for invasive mechanical ventilation (IMV) and length of hospital stay. The Wilcoxon, Mann-Whitney and unpaired student t tests were used. Results: Ninety-nine patients were included, with a mean age of 65.4 ± 14 years, of which 47 (47.5%) were male and 52 (52.5%) were female. Reduced ejection fraction was observed in 77.8% of patients, whilst 22.2% had a diagnosis of HF with preserved EF. The decompensation clinical classifications were: dry and warm = 7 (7.1%), wet and warm = 72 (72.7%), wet and cold = 15 (15.1%) and dry and cold = 5 (5.1%). The average left ventricular ejection fraction was 38.3% ± 15. AKI ocurred in 22 patients (22.2%). Comparison between patients who evolved with and without AKI showed higher mortality (36.4% vs 10.4%, p = 0.004) and the need for IMV (54.5% vs 13%, p = 0.0001) in the first group. There was no significant difference regarding the length of in-hospital stay (22.9 ± 19 vs 18.8 ± 16 days, p = 0.26). Conclusions: The occurrence of AKI was frequent in patients with decompensated HF requiring hospitalization, affecting approximately one out of five patients. This complication was significantly associated with increased mortality and the need for IMV during hospitalization.

Left atrial dysfunction is associated with exercise intolerance and poor prognosis in heart failure (HF). The effects of exercise training on atrial function in patients with HF with mid-range ejection fraction (HFmrEF) are unknown. The purpose of the present study was to assess the effects of a 12-weeks supervised concurrent, aerobic continuous plus resistance, exercise training (SCT) pro-gram on left atrial function of patients with HFmrEF. The study included 70 stable patients, who were randomly assigned into two groups: SCT with (three session/week) or a control (CON) group directed to follow contemporary exercise preventive guidelines at home. Before starting the training program and at 12-weeks, all patients performed: ergometric test, 6-minute walk test and echocardiography. At 12-weeks, exercise duration at ergometric test and distance walked at 6-minute walk test presented a significant greater increase in the SCT compared to control (be-tween-groups p 0.0001 and p 0.004 respectively). Peak atrial longitudinal strain and conduit strain presented an increase of 29% and 34% respectively in the SCT and were unchanged in the CON (between-groups p 0.008 and p 0.001 respectively). Peak atrial contraction strain increased of 21% in the SCT with no changes in the CON (between-groups p 0.002). Left ventricular global longi-tudinal strain increased significantly SCT compared to control (between-groups p 0.03). In con-clusions SCT improved left atrial and left ventricular function in HFmrEF

Background: The 6-minute walk test (6MWT) is a simple and low-cost method that allows assessment of functional capacity in patients with heart failure (HF). However, the prognostic role of 6MWT in HF remains uncertain. Objectives: We aimed to evaluate the 6MWT as a predictor of mid-term adverse outcomes in patients with HF with mid-range and reduced ejection fraction. Methods: Prospective single-center cohort study that included patients with HF with an ejection fraction under 50% at a specialized outpatient HF service. Patients underwent the 6MWT on admission and were compared according to the distance walked: Group I walked ≥350 meters and group II <350 meters. The primary outcome was a composite of death from any cause or hospitalization for HF decompensation in one-year follow-up. Secondary outcomes were the components of the primary outcome in an isolated analysis. Results: Sixty patients were included, 43.3% male, with a mean age of 61.1 ± 12.9 years and ejection fraction 34.3 ± 10.1%. 52 patients (86.7%) were on guideline-directed triple therapy for HF. The average distance walked in the 6MWT was 395.1 ± 98.8 meters, with 40 patients (66.7%) in group I and 20 (33.3%) in group II. The primary outcome in groups I and II were, respectively, 15,0% and 35,0% (p=0.05). One-year mortality was 5.0% vs 15.0% (p=0.18) and the hospitalization rate was 10.0% vs 20.0% (p=0.28). Conclusions: There was no association of distance <350 meters in the 6MWT with the primary outcome in patients with HF. Despite the higher occurrence of outcomes in group II, the difference was not statistically significant in this analysis. On a selective basis, the 6MWT may be a useful tool for prognostic stratification in HF, if combined with other methods.

Background This paper draws learnings and successes based on field implementation experience spanning four years (2016–2019) of implementing CLTS by Prince of Peace Orphans and Widows Vision, a community-based organization located in Kaberamaido district in eastern Uganda. Methods The study aimed to document, disseminate and inform from an evidence-based point of view how adaptation and collaborative engagements triggers learning from mistakes to inform iterative changes from improvements and success.This is a descriptive paper that used project documents review based on field implementation experience. Existing project reports were synthesised, collated and curated for evidence. Data were drawn from project reports and records to inform narratives in writing. Implementation of the project was executed in homogenous rural communities occupied by people of the same dialect, cultural and social settings. Results We note that success in CLTS implementation can hardly be achieved by merely following prescriptions in handbooks and guidelines but rather by devising innovative community engagement and other participatory and community-driven techniques that foster adaptive management, promote ownership, and buy-in.Having learned from our failures, we used data to inform decisions and transformatively deviated from traditional CLTS implementation and introduced high impact and innovative approaches such as the use of CLTS helpdesks and Situation room, the Pamoja approach, learning labs and iterative feedback loops, innovatively tackling slippage and carefully introducing the follow-up mandona approach. These enhanced experiential learning and ultimately resulted in sustained sanitation behaviour. Conclusions The CLTS approach as outlined in the handbook needs to be flexibly adapted to address contextual needs. Reflective and learning sessions reinforced with routine feedback loops from implementers and beneficiaries yields tremendous results, propagates experiential learning, and ultimately results in a transformative deviation from undesirable to desired sanitation behaviours. These innovative approaches once carefully blended have proved to be sustainable, are adaptable and can work in an even larger scale and in a variety of contexts.

Natural fibers are being increasingly used in different areas of engineering, including as composite reinforcement. Among these fibers, carauá stands out for its good mechanical properties and adherence to resin. Nevertheless, little is known about the behavior of this material in the manufacture of a composite or whether classic failure theory can be used in this case. In this context, the present study assesses the mechanical properties of two laminas made of unidirectional curauá fiber with volumetric fiber percentages of 30 % and 22 %, and compares the results with the values obtained for four failure criteria reported in the literature, using analysis of variance (ANOVA). To that end, tensile tests were conducted in the direction of the fiber and at other loading angles, in addition to iosipescu shear tests. The results show that the maximum stress criterion does not represent the failure behavior of these materials and that the best was the Hashin criterion.

High-flow Nasal Cannula (HFNC) oxygen therapy is gaining traction globally as a treatment for respiratory failure. There are several physiological benefits and there may be a growing patient preference for HFNC. In this narrative review, we aim to outline the basic mechanisms of HFNC, who can use it and review the literature regarding its utility both in the critical care setting, as well as in the home setting for chronic hypercapnic respiratory failure with an emphasis on Chronic Obstructive Pulmonary Disease (COPD). The role of non-pharmacological interventions like non-invasive ventilation (NIV) and HFNC in the prevention of hospital readmissions following acute exacerbations of COPD (AECOPD) is an area of increasing importance because randomised controlled trials and systematic reviews have found measures like nurse-led predischarge bundles to be clinically ineffective and to have a high cost per quality adjusted life year. This review therefore considers the evidence of NIV vs HFNC in the context of AECOPD and the application of HFNC at home in the prevention of AECOPD. We also look at applications of HFNC in specific settings, such as in the peri-operative period, emergency department, acute (mainly Critical Care) setting including in immunocompromised patients and palliative care.

House construction is a unique characteristic of the swamp lands in Banjarmasin. Foundations for swampy soil require special handling. The weakness of wood materials and the inability of wood pillar foundations to support building loads are the primary causes of building problems in these swampy areas. Mistakes in foundation construction often arise from the need to expand houses to two stories or renovations. The load-bearing capacity of the wood pillar foundations used is very limited. This study aims to determine the weaknesses of wood pillar foundations to address signs of damage in house construction on swamp land. Field observation research, including the examination of house buildings and individual objects, was conducted at several construction sites in Banjarmasin as part of this study. Data presentation is descriptive. The results indicate that weak wood pillar foundation construction is characterized by damaged piles and floor subsidence. The small size of the wood pillars also limits the load-bearing capacity. The presence of broken 'sunduk' elements is one of the causes of this foundation damage. This research provides new insights into the weaknesses of wood pillar foundations and offers repair recommendations to enhance the resilience and stability of buildings on swamp land.

Serine/arginine-rich splicing factors (SRSF) are a family of proteins involved in RNA metabolism, including pre-mRNA constitutive and alternative splicing. The role of SRSF proteins on mitochondria activity has already been shown for SRSF6 but SRSF4 altered expression has never been reported as disease causing. An 8-year-old patient admitted to the Hematology Unit because of leukopenia, lymphopenia, and neutropenia showed a missense variant of unknown significance on the SRSF4 gene (p.R235W) found by Whole Genome Sequencing analysis and inherited by the mother who suffered from mild leuko-neutropenia. Both patients showed lower SRSF4 protein expression compared to HD and altered mitochondrial function and energetic metabolism, which appeared associated with low mTOR phosphorylation and an imbalance in proteins regulating biogenesis (i.e., CLUH) and mitochondrial dynamics (i.e., DRP1, OPA1). Transfection with the wt-SRSF4 gene restored the mitochondrial function. In conclusion, this study shows that the de-scribed variant of the SRSF4 gene is pathogenetic and causes reduced SRSF4 protein expression, which leads to cells’ mitochondrial function impairment. Since mitochondrial function is crucial for hematopoietic stem cells maintenance and some genetic bone marrow failure syndromes display mitochondrial defects, SRSF4 mutation could have substantially contribute to the clinical phenotype of our patient.

Background: Lung CT provides an effective modality to evaluate patients with suspected COVID-19. However, overlapping imaging findings with cardiogenic pulmonary oedema have been reported. Reports comparing lung CT features of these diseases have not been elaborated. Thus, we aimed to investigate these gaps in the knowledge regarding low-dose lung CT features of patients with COVID-19 pneumonia with those with acute heart failure (HF). Methods: This retrospective analysis enrolled hospitalized patients with COVID-19 (n=10) and acute heart failure (n=9) that exclusively underwent low-dose lung CT scans within 24-hours of admission. Clinical and lung CT characteristics were collected and analysed. Results: Ground-glass-opacities (GGO) appearance has been recorded in all subjects in HF and COVID-19 group. There was no significant statistical difference between the two groups for rounded morphology, consolidation, crazy paving pattern, lesion distribution, parenchymal band (P> 0.05). However, diffuse lesions were more frequent in HF cases (55.6% vs. 0%) than in COVID-19 pneumonia, which had predominantly multifocal pattern. Notably, CT images in HF patients were more likely to have signs of interstitial tissue thickening such as the interlobular septums, fissures and peribronchovascular interstitium (55.6% vs 0%, 88.9% vs 20% and 44.4% vs 0%,respectively), as well as cardiomegaly (77.8% vs 0%), increased artery to bronchus ratio (55.6% vs 0%), and pleural effusions (77.8% vs 0%). Conclusions: Major overlaps of lung CT imaging features existed between COVID-19 pneumonia and acute HF cases. However, signs of fluid redistribution are clues that favour HF over COVID-19 pneumonia.

Repeated desaturation of oxyhemoglobin, micro-arousals, which are typical in obstructive sleep apnea syndrome (OSAS), have negative effects on the health of patients, leading to a wide range of complications such as cardiovascular (arterial hypertension, pulmonary hypertension, chronic heart failure, arrhythmias, myocardial infarction) cerebrovascular (strokes), metabolic (insulin resistance, obesity, diabetes mellitus, metabolic syndrome), gastrointestinal (non-alcoholic liver disease), urinary (chronic renal failure), neuropsychiatric complications and a wide range of malignancies. This in turn has a multilateral effect on familial, occupational and social life, as well as increasing the risk of road traffic accidents or accidents at workplace. Awareness, timely screening and prevention of complications play an important role in the diagnosis and treatment of comorbid conditions. This review focuses on comorbidities in OSAS and the effect of CPAP therapy on their prognosis.

We describe real-world use of mavacamten in 50 patients with oHCM. Consistent with EXPLORER-HCM and VALOR-HCM, we report significant improvement in wall thickness, mitral regurgitation, left ventricular outflow tract obstruction and NYHA class. Moreover, in our center’s experience, neither arrhythmia burden, nor contractility have worsened in the vast majority of patients: We note a clinically insignificant mean decrease in left ventricular ejection fraction (LVEF), with only two patients requiring temporary mavacamten discontinuance for LVEF < 50%. Adverse events were rare, unrelated to mavacamten itself, and seen solely in patients with disease too advanced to have been represented in clinical trials. Our multidisciplinary pathway enabled us to provide a large number of patients with a novel closely-monitored therapeutic within just a few months of commercial availability. These data lead us to conclude that mavacamten, as a first-in-class cardiac myosin inhibitor, is safe and efficacious in real-world settings.

Background : ATPase inhibitor factor-1 (IF1) preserves cellular ATP under conditions of respiratory collapse, yet the function of IF1 under normal respiring conditions is unresolved. We tested the hypothesis that IF1 promotes mitochondrial dysfunction and pathological cardiomyocyte hypertrophy in the context of heart failure (HF). Methods and results Cardiac expression of IF1 was increased in mice and in humans with HF, downstream of neurohumoral signaling pathways and in patterns that resembled the fetal-like gene program. Adenoviral expression of wild type IF1 in primary cardiomyocytes resulted in pathological hypertrophy and metabolic remodeling as evidenced by enhanced mitochondrial oxidative stress, reduced mitochondrial respiratory capacity, and the augmentation of extra-mitochondrial glycolysis. Similar perturbations were observed with an IF1 mutant incapable of binding to ATP-synthase (E55A mutation), indication that these effects occurred independent of binding to ATP synthase. Instead, IF1 promoted mitochondrial fragmentation and compromised mitochondrial Ca2+ handling, which resulted in sarcoplasmic reticulum Ca2+ overloading. The effects of IF1 on Ca2+ handling were associated with the cytosolic activation of CaMKII and inhibition of CaMKII or co-expression of catalytically dead CaMKIIδC was sufficient to prevent IF-1 induced pathological hypertrophy. Conclusions IF1 represents a novel member of the fetal-like gene program that contributes to mitochondrial dysfunction and pathological cardiac remodeling in HF. Furthermore, we present evidence for a novel, ATP-synthase independent, role for IF1 in mitochondrial Ca2+ handling and mitochondrial- to nuclear crosstalk involving CaMKII.

Systemic amyloidosis is a multisystem illness characterized by fibrillary protein deposition, which causes dysfunction in the afflicted organ systems. Its diagnosis is frequently delayed since the disease's symptoms are unpredictable and non-specific. Its two main variants are light chain (AL) amyloidosis and transthyretin-related ATTR amyloidosis, which has both a sporadic (wildtype, ATTRwt) and hereditary (mutated, ATTRv) subtype. We discuss a case of Amyloidosis emerging in the kidneys and heart as a result of chronic inflammation caused by failure to treat TB, as well as its typical radiological characteristics, clinical presentation, imaging and instrumental evaluations, and therapeutic plan. This case report serves as a good reminder to medical personnel to ensure thorough patient follow-up in order to avoid extremely unusual and late complications resulting from treatment default.

Feline immunodeficiency virus (FIV) is a lentivirus in the family Retroviridae that infects domestic cats resulting in an immunodeficiency disease featuring a progressive and profound decline in multiple sets of peripheral lymphocytes. Despite compelling evidence of FIV-associated immunopathology, there are conflicting data concerning the clinical effects of FIV infection on host morbidity and mortality. To explore FIV-associated immunopathogenesis and clinical disease, we experimentally inoculated a cohort of 4 specific pathogen free kittens with a biological isolate of FIV clade C and continuously monitored these animals along with 2 uninfected control animals for more than 13 years, from the time of inoculation to the humane euthanasia endpoint. Here we report the results obtained during the late asymptomatic and terminal phases of FIV infection in this group of experimentally FIV-infected cats.

The objective was to compare the failure loads of glass ceramic, and polymer crowns against yttria-partially stabilized zirconia (Y-PSZ) crowns with varying yttria concentrations. Monolithic crowns of zirconia (Cercon XT, Katana UTML, BruxZir Anterior), glass ceramic (Celtra press, IPS e.max press, Lisi press), and polymeric materials (Trilor, Juvora, Pekkton) were fabricated and cemented to epoxy abutments. The total number of specimens was 135 for crowns and 135 for discs (15 specimens per material type and design). A universal testing machine was used to perform compressive loading of all crowns to failure with a steel hemisphere along the longitudinal axis of the abutments. Energy dispersive spectroscopy (EDS) was used to identify the concentration (mol% yttria-partially stabilized zirconia) for each zirconia brand. The data were analyzed using a generalized linear model and regression analysis. The results revealed significant differences (P < .05) in mean failure loads for different crown materials: Trilor (6811 ± 960 N) > Juvora (5215 ± 151 N) > Cercon (4260 ± 520 N) = BruxZir (4186 ± 269 N) = e.max (3981 ± 384 N) > Katana (3195 ± 350 N) = Lisi (3173 ± 234 N) = Pekkton (3105 ± 398 N) > Celtra (2696 ± 393 N). EDS showed that the zirconia materials contained yttria at different concentrations (BruxZir = 5Y-PSZ, Cercon = 4Y-PSZ, Katana = 3Y-PSZ). The yttria concentration had a significant effect on the failure load of the Katana (3Y-PSZ) crowns, which revealed lower failure loads than the Cercon (4Y-PSZ) and BruxZir (5Y-PSZ) crowns. New zirconia materials are provided with different yttria concentrations (3Y-, 4Y-, and 5Y-PSZ). Since a higher yttria concentration increases the translucency, clinicians should be aware that 4-5 wt% yttria-partially stabilized zirconia materials provide comparable or higher mechanical properties than e. max glass ceramic for dental application of crowns.

Background: The global pandemic of coronavirus disease 2019 (COVID-19) resulted to many deaths from fulminant respiratory failure. Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There has been great concern regarding the impact of COPD on COVID-19 illness. Methods: Data from the Philippine CORONA Study were analyzed to determine the association of COPD and COVID-19 in terms of mortality, disease severity, respiratory failure, mechanical ventilation, and lengths of stay in the intensive care unit (ICU) and hospital. The influence of smoking on COVID-19 disease severity and mortality were also reviewed. Results: A total of 10,881 patients were included in the study and 156 (1.4%) patients had been diagnosed with COPD. Majority of COVID-19 patients with COPD had other existing comorbidities: hypertension, diabetes mellitus, chronic cardiac disease, and chronic kidney disease. COPD patients more commonly present with severe or critical COVID-19. COPD patients with COVID-19 were at higher risk to experience in-hospital mortality, respiratory failure, and to be admitted in the ICU. Smokers were more likely to present with higher COVID-19 severity and experience in-hospital mortality. Conclusion: Our study supports that the growing evidence that COPD among COVID-19 patients is a risk for higher mortality, more severe form of COVID-19, higher ICU admission, and higher respiratory failure needing ventilatory support. Smoking increases risk for developing severe COVID-19 and mortality.

Abstract Sodium glucose cotransporter type 2 inhibitors are a new class of drugs acting on cardiovascular system, renal and metabolism in a multiple way. Indeed, even their principal action is on the transporter of sodium and glucose in the convoluted distal tubule, they have multiple actions as antifibrotic and endothelial protective action. Their principal mechanism consist in the loss of sodium and glucose. Therefore, they have effect on blood pressure and glucose metabolism. In a first period their use has been in the diabetic general population, later on some studies documented their activity in non-diabetic general population, in heart failure in chronic kidney disease. Only in recent years several small studies documented their efficacy in diabetic and non-diabetic kidney transplant patients, larger studies are few and very recent and open new ways for these drugs

In this paper we present experimental results concerning Acoustic Emission (AE) recorded during cyclic compression tests on two different kinds of brittle building materials, namely concrete and basalt. The AE inter-event times were investigated through a non-extensive statistical mechanics analysis which shows that their decumulative probability distributions follow q-exponential laws. The entropic index q and the relaxation parameter q  1=Tq, obtained by fitting the experimental data, exhibit systematic changes during the various stages of the failure process, namely (q; Tq) linearly align. The Tq = 0 point corresponds to the macroscopic breakdown of the material. The slope, including its sign, of the linear alignment appears to depend on the chemical and mechanical properties of the sample. These results provide an insight on the warning signs of the incipient failure of building materials and could therefore be used in monitoring the health of existing structures such as buildings and bridges.

Recently, Electric Two-Wheelers ETW are changing the face of the global automotive market. This study focused on selecting proper material and mechanical isolation gap to design a protective enclosure for the battery pack of ETW. The integration of the Failure, Modes, Mechanism and Effect Analysis (FMMEA) method is utilized to develop the interface matrix and the severity index of different components of the enclosure. By analyzing different forces from the road conditions, dynamics during turn, acceleration, and deceleration with the enclosure, it becomes a crucial load-bearing element. Employing Finite Element Modeling (FEM), structural strength using materials like AL6061, Q235, C22000, DC 01 and Teflon are assessed under varying static, dynamic and thermal conditions. Modal analysis is conducted to observe the excitation frequencies where the maximum deformation for the metal enclosure is observed beyond 500Hz. AL6061 material that can withstand the stresses and deformations that are under allowable stress limits with negligible deformation is most preferable material based on the results. Minimal of 2.5 mm gap to be provided in case of metal casing and 10mm in case of Teflon is proven.

Cadaver bone is possibly the most common transplant material used today. Common types of cadaver bone transplants are freeze dried bone allografts and xenografts. In the case of freeze dried bone allograft transplants, it was theorized that these materials mineralize by way of osteoinduction and stimulating osteogenesis. However, these theories have been proven false. It has been proposed that these materials mineralize via osteoconduction however, there are no studies to support this hypothesis. This study was undertaken to determine how these transplants mineralize and what type of bone they produce. Materials and Methods: This study is a histological analysis of human cadaver bone graft healing from the incipient stages of mineralization through completed mineralization. All cadaver bone grafts used for evaluation in this study were particulate bone graft materials in the maxilla or mandible. No block grafts were evaluated. Results: The mineralization of cadaver bone transplants was produced by an inflammatory response to the transplanted tissue. The histologic findings of the mineralized bone produced by this process was sclerotic bone. No resorption of cadaver bone graft particles was found. When loaded the sclerotic bone was found to fail through an accumulation of microfractures.Conclusions: Particulate freeze-dried bone allografts and xenografts do not heal via the normal processes of mineralization. Cadaver bone grafts produce significant inflammation and are hypothesized to mineralize by a process termed antigenic ossification. The process of antigenic ossification produces sclerotic bone that is not capable of self-repair which can ultimately lead to bone failure.

Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic method. The multitude of different etiological factors, the diversity of the clinical picture and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated diseases that in their natural course can lead to myocardial involvement, but also the iatrogenic cause of myocarditis due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, changes in ECG and echocardiography has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive diagnostic gold standard for diagnosis and clinical follow-up of thses patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening patients with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high.

Although acute heart failure (AHF) is a common disease associated with significant symptoms, morbidity and mortality, the diagnosis, risk stratification and treatment of patients with hypertensive acute heart failure (H-AHF) still remain a challenge in modern medicine. Despite great progress in diagnostic and therapeutic modalities, this disease is still accompanied by a high rate of both in-hospital (from 3.8% to 11%) and one-year mortality (from 20% to 36%). Considering the high rate of re-hospitalization (22% to 30% in the first three months), the treatment of this disease represents a major financial blow to the health system of each country. This disease is characterized by heterogeneity in precipitating factors, clinical presentation, therapeutic modalities and prognosis. Since heart decompensation usually occurs quickly (within a few hours) in patients with H-AHF, establishing a rapid diagnosis is of vital importance. In addition to establishing the diagnosis of heart failure itself, it is necessary to see the underlying cause that led to it, especially if it is de novo heart failure. Given that hypertension is a precipitating factor of AHF and in up to 11% of AHF patients, strict control of arterial blood pressure is necessary until target values are reached in order to prevent the occurrence of H-AHF, which is still accompanied by a high rate of both early and long-term mortality.

The decompensation trajectory check is a basic step to assess the clinical course and to plan future therapy in hospitalized patients with acute heart failure (ADHF). Due to the atypical presentation and clinical complexity, trajectory checks can be challenging in the oldest old patients with acute HF. Point of care ultrasound (POCUS) proved to be helpful in the clinical decision-making of patients with dyspnea, but no study has attempted to verify its effectiveness in predicting determinants of HF in-hospital worsening. In this single-center prospective study, we consecutively enrolled patients aged 75 or older hospitalized with acutely decompensated HF in a tertiary care hospital. All the patients underwent complete clinical examination, blood tests, and POCUS including Lung Ultrasound, Focused Cardiac Ultrasound, Pleural Effusion score (PEFs), and Inferior Vena Cava (IVC) assessment. Out of 184 patients hospitalized with ADHF enrolled in the study, sixty experienced HF in-hospital worsening. No differences were found among patients with HF worsening and controls in terms of age, gender, frailty, and left ventricular ejection fraction. By multivariable logistic analysis, total PEFs [aOR: 1.15 (CI95% 1.02– 1.33), p = 0.043], and IVC collapsibility [aOR: 0.90 (CI95% 0.83 – 0.95), p = 0.039] emerged as independent predictors of acute HF worsening after extensive adjustment for potential confounders.

Introduction and objectives: arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease defined by the progressive replacement of the ventricular myocardium with fibroadipose tissue, which can act as a substrate for arrhythmias, sudden death, or even give rise to heart failure (HF). Sudden death is frequently the first manifestation of the disease, particularly among young patients. The aim of this study is to describe a new pathogenic variant in the PKP2 gene. Methods: A descriptive observational study that included 8 initially non-interrelated families with a diagnosis of ACM undergoing follow-up at our HF and Familial Cardiomyopathies Unit, who were carriers of the NM_004572.3:c.775_776insG; p. (Glu259Glyfs*77) variant in PKP2 gene. The genetic testing employed next-generation sequencing for the index cases, and the Sanger method for the targeted study with family members. We compiled personal and family histories, demographic and clinical characteristics, data from the additional tests at the time of diagnosis, and arrhythmic events at diagnosis and during follow-up. Results: We included 47 subjects, of whom 8 were index cases (17%). Among the evaluated family members, 16 (34%) were carriers of the genetic variant, 3 of whom also had a diagnosis of ACM. The majority were women (26 patients; 55.3%), with a mean age on diagnosis of 48.9 ± 18.6 years, and a median follow-up of 39 [24-59] months. Worthy of note are the high incidence of arrhythmic events as the form of presentation and in follow-up (21.5% and 20.9% respectively), and the onset of HF in 25% of the sample. The most frequent ventricular involvements were right (4 patients 16.7%) and biventricular (4 patients 16.7%); we found no statistical differences in any of the variables analysed. Conclusions: This variant is a pathogenic variant of gene PKP2 that has not previously been described and is not present in the control groups associated with ACM. It has incomplete penetrance, a highly variable phenotypic expressivity, and was identified in 8 families of our geographical area in Malaga (Andalusia, Spain), where we can establish a founder effect and describe the clinical and risk characteristics.

Background: Left ventricular noncompaction (LVNC) is a genetically determined cardiomyopathy, that occurs following a disruption of endomyocardial morphogenesis. The purpose of this study was to identify the clinical characteristics and genetic profile of children with LVNC. Methods: From February 2008 to July 2020, a total of 32 children (median 11.5 years) with LVNC were prospectively enrolled and followed up for the median of 4.02 years. Diagnosis was made based on characteristic features of LVNC in echocardiography and cardiovascular magnetic resonance (CMR). Patients’ clinical symptoms, family history, ECG, Holter ECG and genetic tests were also evaluated. Results: The most common presenting symptom was heart failure (31% of children). ECG abnormalities were noted in 56% of patients. The most prominent features were ventricular arrhythmias, sinus bradycardia and paroxysmal third-degree atrioventricular block. Most of the patients (94%) met the criteria for LVNC and CMR confirmed this diagnosis in 82% of cases. The molecular etiology was found in 53% of children. Conclusion: Although heart failure and arrhythmias were very frequent in our study group, thromboembolic events and genetic syndromes were rare. For accurate and reliable assessment of children with LVNC, it is necessary to get to know their family history and detailed clinical profile.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterized by multiple risk factors and associated conditions. HFpEF prevalence is rising, and its prognosis remains poor after the first hospitalization. Using a two-hit HFpEF murine model, we aimed at studying cardiac reverse remodelling after stopping the causing stress (Angiotensin II [AngII]) and a high-fat diet [HFD]; MHS) and introducing voluntary exercise. We studied in young male and female C57Bl6/J mice fed or not with an HFD (60% calories from fat) the cardiac response to AngII (1.5 mg/kg/day for 28 days). Then, MHS was stopped, and VE was started for another four weeks (RR). We studied the effects of MHS and RR on the circulatory microRNA (miR) profile (miRNome) and the myocardial miRNome to characterize the cardiac and non-cardiac response of small RNAs. AngII alone and MHS but not the HFD caused cardiac hypertrophy (CH), left ventricular (LV) concentric remodelling and left atrial enlargement in male mice. HFD-induced CH and LV concentric remodelling only in female mice. Four weeks after RR, CH, LV concentric remodelling and atrial enlargement were reversed. We performed bulk circulatory and LV miR sequencing. We did not observe differences linked to biological sex. RR restored normality for circulatory miRNome, whereas LV miRNome remained relatively similar to the one after MHS. Among the 25 most abundant circulatory miRs, ten were modulated by MHS (9 upregulated). In the LV, 8 of the 25 most abundant miR were upregulated by MHS, and 10 were downregulated. MiRNomes from AngII, HFD or MHS shared many common modulated miRs (32), suggesting that the overall response of organs producing the bulk of circulatory small non-coding RNA was similar even for seemingly different stress.

Primary failure of eruption (PFE) is a rare non-syndromic condition involving total or partial non-eruption of posterior teeth, in the absence of mechanical obstruction. This paper presents the case of a healthy girl referred at age 4 years for asymmetry of upper arch. Clinical examination confirmed a slight shift of the upper midline to the left, with no erupted teeth distal to the upper left canine and left posterior open bite. Panoramic X-ray showed delayed intra-osseous development of lateral left upper teeth compared to the right side. Clinic and radiographic follow-up during the next 9 years showed that 26 has not erupted by almost 13 years of age, 27 has delayed development and an unusual shape and there is agenesis of 24, 25. Genetic analysis using the PTH1R single gene sequencing did not detect any known disease-causing or rare pathogenic variants that could explain the patient's phenotype. Even when detected early, PFE rises difficult problems with regard to diagnosis and ortho-surgical treatment planning due to the impossibility to accurately predict the evolution. Tooth agenesis on the same arch worsens the prognosis and adds challenges to planning the treatment. Close long-term follow-up and timely adjustment of treatment plan in accordance to the evolution of the case are needed.

Cancer treatment with specific chemotherapeutic agents has been well documented to have an adverse impact on female fertility leading to premature ovarian failure (POF). The objective of this study was to investigate if chemotherapeutic induced POF can be reversed with an infusion of autologous nucleated peripheral blood cells (PBMC). To reach our goal, mice were treated with a single intraperitoneal injections of busulfan and cyclophosphamide to induce POF. This was followed by transfusion of PBMC. The ovarian morphology and functional parameters were monitored by radioimmunoassay, real-time PCR, immunofluorescence and immunohistochemistry analysis. Our study showed that chemotherapy (CTX) protracted estrous cycle period and repressed E2 production. CTX decreased the expressions of steroidogenesis markers- CYP-17 synthesis, StAR and Connexin-43 protein expression from the ovarian follicles. We also observed reduced numbers and sizes of the primordial and primary follicles in CTX-treated mice compared to untreated controls (P < 0.05). When both CTX and untreated –control groups were stimulated with gonadotrophin, the control group produced ten times more ova than the CTX group. Finally, the treatment of premature ovarian failure induced by CTX with autologous PBMC transfusion resulted in over-expression and a statistically significant increase in several stem cell markers and restoration of fertility. Infusion with PBMC in CTX further decreased the estrous cycle length by 2.5 times (P < 0.01). We found that transfusion of autologous PBMC to mice with chemotherapy induced POF was very effective at restoring fertility. These results are similar to other studies using bone marrow derived mesenchymal stem cells.

Heart failure with preserved ejection fraction (HFpEF) remains a poorly characterized syndrome with many dark aspects related to different patients profile, various associated risk factors and wide aetiologies. It comprises several pathophysiological pathways related to endothelial dysfunction, myocardial fibrosis, extracellular matrix deposition and high inflammatory response. Up to now, it has been described only for clinical appearance and most common associated risk factors without an effective characterization of biological processes responsible for cardiovascular deteriorations. Recent advances in laboratory and metabolomic researches showed that HFpEF appears strictly related to specific cells and molecular mechanisms dysregulation. Some biomarkers are capable to early identify these processes adding new insights into diagnosis and risk stratification. Additionally recent advances on intermediate metabolites reflecting provide relevant information on intrinsic cellular and energetic substrate alterations. The systematic combination of clinical imaging and laboratory data may lead to a precision medicine approach providing prognostic and therapeutic advantages. Current review reports traditional and emerging biomarkers recently investigated in HFpEF setting, and it purpose a new diagnostic approach based on integrative information achieved from risk factors burden, hemodynamic dysfunction and biomarkers signature partnership.

Background and Objectives: Ischemic and idiopathic heart failure are two different etiologies, however reactive cardiac fibrosis together with impaired vasculogenesis has been described in both of them. Implication of main proangiogenic factors as: angiogenin, agiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) has been described mainly in experimental models of heart failure. However, differences in molecular pathways between these cardiomyopathies are still under investigation. In this short communication we aimed to evaluate and compare the expression of pro-angiogenic molecules in the heart tissue of patients with advanced chronic heart failure (CHF) of ischemic and idiopathic etiology. Methods and Results: Heart tissue from left ventricular walls was obtained at transplantation from ischemic heart disease (IHD), idiopathic cardiomyopathy (ICM) patients. Tissue samples were examined using immunohistochemistry for angiogenic molecules. Immunopositivity (I-pos) for angiopoietin-1 was mainly observed in the cardiomyocytes, while I-pos for Ang-2 and Tie-2 receptor mainly in endothelial cells. Procollagen-I (PICP), angiogenin, Ang-1, Tie-2 receptor, were similarly expressed in IHD and ICM patients. In contrast, endothelial immunopositivity for Ang-2 was higher in IHD samples compared to ICM (p=0.03). Conclusions: Ang-2 expression is different in heart tissue of ICM and ICM patients and distribution of Ang-1 and angiogenin is higher in cardiomyocytes, whereas Ang-2 higher in endothelial cells, suggesting a different pattern of angiogenic stimulation, or at least of altered endothelial integrity. This data may serve for further studies investigating angiogenesis signaling pathways and in HF of different etiology.

In this study, in order to explore the failure mode of ZnO varistors under multiple lightning stroke, a 5-pulse 8/20 μs nominal lightning current with pulse intervals of 50 ms was applied to the ZnO varistors. Scanning electron microscopy (SEM) and X-ray diffractometry (XRD) were used to analyze the microstructure of the material. The failure processes of ZnO varistors caused by multiple lightning impulse current were described. The performance changes of ZnO varistors after multiple lightning impulses were analyzed from macro and micro perspectives. According to the results of this study’s experiments, the macroscopic failure mode of the ZnO varistors after multiple lightning impulse was that the electrical parameters deteriorate rapidly with the increase of the number of impulse groups, and finally destroyed by side-corner cracking. The microstructural examination indicated that after the multiple lightning strokes, the proportion of Bi in the several crystal phases had been converted, the grain size of ZnO varistors became smaller, and the white intergranular phase (Bi-rich grain boundary layer) increased significantly. The failure mechanism was thermal damage and grain boundary structure damage caused by temperature gradient thermal stress generated by multiple lightning current.

Background: Children suffering from COVID-19 constitute about 10% of the entire population infected with the virus. In most of them, we observe asymptomatic or mild course; however, about 1% of affected children require a stay in the pediatric intensive care unit (PICU) due to the severe life-threatening course. The risk of respiratory failure, as in adults, is associated with the coexistence of concomitant diseases. The aim of our study was to analyze patients admitted to PICUs due to severe course of SARS-CoV-19 infection. Methods: A retrospective multi-center study, the analysis covered all children with a confirmed diagnosis of SARS-CoV-2 virus infection, who were admitted to PICUs, in the period from November 2020 to August 2021. We studied epidemiological and laboratory parameters, and the endpoint – survival or death. Results: The study analyzed 45 patients (0.075% of all children hospitalized in Poland due to COVID-19 at that time). Mortality calculated in the entire study group was 40% (n=18). Statistically significant differences between the compared groups (survived and died) concerned the parameters of the respiratory system, Lung Injury Score and Pediatric Sequential Organ Failure Assessment . A significant correlation between disease severity and the patient's prognosis was shown by the liver function parameter AST (p=0.028). Analyzing patients requiring mechanical ventilation and assuming survival as the primary outcome, a significantly higher oxygen index on the first day of hospitalization, lower pSOFA scores and lower AST levels (p: 0.007; 0.043; 0.020; 0.005; 0.039, respectively) were found. Conclusions: As in adults, children with comorbidities are most frequently at risk of severe SARS-CoV-2 infection. Increasing symptoms of respiratory failure, the need for mechanical ventilation and persistently high values of aspartate aminotransferase are indicators of poor prognosis.

Introduction: The construction of a house with a stage structure is the uniqueness of Banjarmasin's swampland. Particularly, foundations for swampy terrain necessitate special handling. Building material defects and the basic inability to modify the use and design of wood pillar foundations are the main causes of house building problems. The very limited capacity of a wooden pillar foundation makes house buildings collapse frequently. Purpose of the study: The aim of the study is to determine the weaknesses of the wooden pillar foundations by examining the indications of damage to the house structure. Methods: Field observation investigations, including housing and individual object observations, will be carried out at multiple construction sites in Banjarmasin (Indonesia) as part of this study. The way the data is presented is descriptive. Result: The weak construction of a wooden pillar foundation explains some indications of house building damage, such as broken wooden pillars and floor settlement. The existence of evidence that there is a broken 'sunduk’ element is one of the causes of damage to this foundation. The small size of the wooden poles also makes the load-bearing capacity limited.

Failure of wind turbines is a multi-faceted problem and its monetary impact is often unpredicted. In this study, we present a novel application of survival analysis on wind turbine reliability performance that includes accounting of previous failures and history of scheduled maintenance. We investigate the operational, climatic and geographical factors which affect wind turbine failures and model the risk rate of wind turbine failures based on data from 109 turbines in Germany operating during a period of 19 years. Our analysis showed that adequately scheduled maintenance can increase the survivorship of wind turbine systems and electric subsystems up to 2.8 and 3.8 times, respectively compared to the ones without scheduled maintenance. Geared-drive wind turbines and their electrical systems were observed to have 1.2- and 1.4-times higher survivorship, respectively, compared to direct-drive turbines and their electrical systems. It is also found that survivorship of frequently-failed wind turbine components, such as switches, is worse in geared-drive than in direct-drive wind turbines. We show that survival analysis is a useful tool for guiding the reduction of operating and maintenance costs of wind turbines.

Studies have found critical software malfunctions responsible for some of the worst accidents in recent times. These malfunctions are often only minor defects that snowball into large problems; a few lines of code is all it takes. Complexity, safety, quality, and resilience are among the key attributes defining a software’s operational success. There are many leading factors for complexity, such as increases in the product size, the rate of requirement changes, and the number and type of stakeholders, and failure to manage these issues efficiently always has the same consequence, i.e., massive failure and sometimes technological catastrophe. This work analyzes some of the architecture, design, and implementation guidelines used as detection and mitigation techniques. It also discusses the safety considerations, as considering how the steam industry has handled safety issues could offer some guidance for ensuring safety. Complexity in such systems also causes some of the worst side effects from the quality auditor's perspective. While failures in the software are hard to predict, one of the most significant ways of showing preparedness is practicing software resilience. New mitigation areas, such as the fragility spectrum and failure obviation, and their usage for building a safer system are analyzed. Also discussed are various architecture styles in practice and the dramatic effect human factors can have on the success of the software being developed.

Beyond plasma glucose-lowering in patients with type 2 diabetes, sodium- glucose cotransporter 2 inhibitors (SGLT2i) significantly reduced the hospitalization for heart failure (HF) and retarded the progression of chronic kidney disease (CKD). Endothelial dysfunction is not only involved in the development and progression of cardiovascular disease (CVD), and is also associated with the progression of CKD. In patients with type 2 diabetes, hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia induce the development of endothelial dysfunction. SGLT2i have shown an improvement in endothelial dysfunction, as assessed by flow-mediated vasodila-tion, in individuals at high risk for CVD. Along with an improvement of endothelial dysfunction, SGLT2i showed improvements in oxidative stress, inflammation, mitochondrial dysfunction, glucotoxicity such as advanced glycation end products signaling and nitric oxide bioavailability. The improvements in endothelial dysfunc-tion and such endothelium-derived factors may play an important role in preventing the development of coronary artery disease, coronary microvascular dysfunction and diabetic cardiomyopathy which cause HF and in retarding CKD. The suppression of the development of HF and the progression of CKD achieved by SGLT2i might have been largely induced by the improvement of vascular endothelial function by SGLT2i.

Dilated cardiomyopathy (DCM) is a common form of cardiomyopathy, characterized by ventricular chamber dilatation and systolic dysfunction, in the absence of coronary artery disease, arterial hypertension, valvular or congenital diseases. DCM is a heterogeneous group of disorders of the myocardium caused by genetic factors, environmental factors, or a combination of both. DCM affects mainly men aged between 20 and 50 years, being considered one of the main causes of heart failure (HF) and the main indication for heart transplantation. Guideline-based HF treatment is the mainstay of management for patients with DCM. In recent years, gene therapy and induced pluripotent stem cells have become promising strategies. In this review, we summarize the relevant clinical issues, and current treatment of DCM patients, including the role of genetic evaluation.

Background A decline in cardiovascular hospitalizations was observed during the initial phases of the COVID-19 pandemic. We examine the continued effect of the pandemic on cardiovascular hospitalizations and the associated mortality rates during the first year of the pandemic in Israel. Methods We conduct a retrospective cohort study using the data of Clalit Health Services, the largest healthcare organization in Israel. We divide the Corona year into six periods (three lockdowns and three post-lockdowns) and compare the incidence rates of cardiovascular hospitalizations and their 30-day mortality during each period to the previous three years. Results The number of non-STEMI hospitalizations during the first year of the pandemic was 13.7% lower than the average of the previous three years (95% CI 11%-17%); STEMI hospitalizations were 15.7% lower (95% CI 13%-19%); and CHF hospitalizations were 23.9% lower (95%, CI 21%-27%). No significant differences in 30-day mortality rates were observed for AMI patients during most of the periods, whereas the annual 30-day all-cause mortality rate of CHF was 23% higher. Conclusions Hospitalizations for AMI and CHF were significantly lower during the first year of the pandemic relative to 2017–9. Mortality rates were higher in the case of CHF patients but not in the case of AMI patients, possibly due a change in the clinical acuity of patients arriving at the hospitals. We conclude that targeted public health messaging should be implemented, together with proactive monitoring in order to identify residual disability in patients that may have received non-optimal treatment during the pandemic.

Much evidence reveals an important link between gut microbiota and the heart. In particular, the gut microbiota plays a key role in the onset of cardiovascular (CV) disease, including heart failure (HF). In HF, splanchnic hypoperfusion causes intestinal ischemia resulting in the translocation of bacteria and their metabolites into the blood circulation. Among these, the most important is the Trimethylamine N-Oxide (TMAO), which is responsible through various mechanisms for pathological processes in different organs and tissues. In this review, we summarise the complex interaction between gut microbiota and CV disease, particularly with HF, and the possible strategies to influence its composition and function. Finally, we highlight the potential role of TMAO as a novel prognostic marker and new therapeutic target of HF.

Background and Objectives: Proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (AF) patients. Left atrial appendage closure (LAAC) may be considered for stroke prevention in patients with AF and contraindications for long-term anticoagulant treatment. We aimed to assess the anticoagulation status and LAAC indications in patients with AF from HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Materials and Methods: HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on March 3, 2022, in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves and moderate to severe mitral valve stenosis. Patients with prior stroke, previous major bleeding, poor adherence to anticoagulants, and end-stage renal disease were considered candidates for LAAC. Results: Two hundred fifty-six patients (mean age 76.6±11.7, 148 males) were included in our analysis. Most of them (n=159; 62%) suffered from persistent AF. Mean CHA2DS2-VASc score was 4.28±1.7, while mean HAS-BLED score was 1.47±0.9. Three out of 3 patients with a CHA2DS2-VASc 0 or 1 (female) received improperly anticoagulants. Sixteen out of 18 patients with a CHA2DS2-VASc 1 or 2 (female) received anticoagulants. Thirty-three out of 235 patients with a CHA2DS2-VASc &gt; 1 or 2 (for female) did not receive improperly anticoagulants. Among 221 under anticoagulant therapy, 191 (86.4%) received non-vitamin K antagonist oral anticoagulants (NOACs) and 30 (13.6%) received vitamin K antagonists. Relative indications for LAAC were present in 64 patients with NVAF (60 had only one risk factor and 2 had two concurrent risk factors). In detail, 36 had a prior stroke, 17 patients had a history of major bleeding, 15 patients reported poor or no adherence to the anticoagulant therapy and 5 had eGFR&lt; 15 ml/min/1.73m2. Moreover, 33 had a HAS-BLED score ≥3. No LAAC treatment was recorded. Conclusions: Anticoagulation status was nearly optimal in a high thromboembolic risk population of cardiology patients, mainly treated with NOACs. One out of four AF patients should be screened for LAAC.

Is there any possible synergic effect of fertility outcome between spindle view-assisted intracyto-plasmic sperm injection (SV-ICSI) with or without assisted oocyte activation (AOA) for patients with low fertilization rate history? To explore the answer, a retrospective study was held in our fertility center by reviewing patients receiving SV-ICSI during 2019/03 to 2023/06. Total 47 pa-tients were included, the fertility outcomes of intervention group (AOA-SV-ICSI, 14 patients) and control group (SV-ICSI, 33 patients), such as fertilization rate, blastocyst formation rate and clin-ical pregnancy rate, were analyzed. The blastocyst formation rate between groups was signifi-cantly higher in AOA-SV-ICSI group (p=0.020), but the fertilization rate and clinical pregnancy rate did not reach any statistical significance. This discovery of increased blastocyst formation rate in low fertilization rate patients could possibly help them in getting more usable embryos in fertility treatment.

The thyroid-heart relationship has a long and articulated history of its own, a history that en-compasses physiological and pathophysiological knowledge, the latter particularly in the context of cardiac diseases such as heart failure, arrhythmias and ischaemic heart disease. In recent years, molecular biology studies, in an experimental context, have highlighted the extraordinary dialogue that exists among the two systems in the field of cardioprotection, being an extremely important area for the treatment of cardiac diseases in both acute and chronic phases. In addi-tion, in the last few years, several studies have been carried out on the prognostic impact of al-terations in thyroid function, including subclinical ones, in heart disease, in particular in heart failure and acute myocardial infarction, with evidence of a negative prognostic impact of these and therefore with the suggestion to treat these alterations in order to prevent cardiac events, such as death. This review provides a comprehensive summary of the heart-thyroid relation-ship.

Regulatory T cells are key immune cells to initiate tolerable immune responses. TGFβ is the key cytokine of regulatory T cells. TGFβ is also the master cytokine to stimulate tissue fibrosis. Systemic sclerosis is an autoimmune disease related to overt organ fibrosis. Thus, systemic sclerosis is a disease related to regulatory T cell over-representation. Besides, many end stage organ failures including heart failure, liver cirrhosis, uremia, and pulmonary fibrosis also related to tissue fibrosis. Thus, TGFβ producing regulatory T cells are also involved in the pathogenesis of these end stage organ failure. Once we know the significance of TGFβ and it induced tolerable immune reactions in the pathophysiology of end organ failure, we can develop better prevention or therapeutic strategies to combat these detrimental disorders.

This paper aims to provide an overall review of degradation, damage evolution and fatigue models in the literature of various engineering materials, mostly metals, and composites.

Background: Anthracyclines form the backbone of many systemic chemotherapy regimens but dose-limiting cardiotoxicity can also lead to reduction in cardiac function and an increased risk of heart failure. Methods: This review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD42022373496). Results: 26 studies met the eligibility criteria including a total of 910 patients. Overall reduction in pooled mean left ventricular ejection fraction (LVEF) post‐anthracyclines in the placebo arms of included randomised-controlled trials was 4.6% (95% CI, 2.7 to 6.6). The trend in LVEF showed a progressive decline until approximately 180 days after which there was no significant change. Those receiving a cumulative anthracycline dose 300 mg/m2 experienced a more profound reduction. The risk of a 10% absolute decline in LVEF from baseline or decline to an LVEF below 50%, the overall pooled risk was 16% (95% CI: 11 to 21; I2 = 77%). Sensitivity analyses by baseline LVEF and trastuzumab treatment status did not yield significant differences. Conclusion: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines are required.

On the aero-engine combustor liner, a phenomenon of overheating resembling a hot spot exists, accompanied by a preferential peeling of the YSZ thermal barrier coating that will negatively affect the service life of the component. The temperature gradient of the hot spot may affect the YSZ fracture pattern.In this paper, the morphological and property changes of YSZ sintering is investigated experimentally, and a coupled analysis of the YSZ Crack Propagation Mode under the hot spot is performed using ABAQUS. The results show that the pore fractal size D of YSZ increases by 15%. Inside the hot spot region, the coating has a shear stress of 75MPa. By inserting Cohesive units globally in the model to simulate the random crack initiation and propagation, unlike the thinning of YSZ layered peeling caused by uniform superheating, hot spot will cause the crack initiation at the tip of the pores inside the coating and the oblique propagation, eventually forming an oblique crack connection through the pores. When the temperature gradient reaches 30K/mm, the crack propagation is 40% greater than in a uniform temperature field; consequently, the YSZ in the hot spot boundary region with a greater temperature gradient results in more severe bulk peeling.

Hepatic encephalopathy (HE) is a form of brain dysfunction that is specifically caused by liver insufficiency and/or portal-systemic shunt. The exact nature of HE is debated, so that conflicting uses of the term HE may cause inconsistencies in its detection and, in turn, issues with its management. This review highlights the meaning of the term HE on the basis of both its historical origins and current consensus. It also provides criteria for the diagnosis of the condition, on the basis of its phenotypes and the risk factors for its occurrence. The procedure for differential diagnosis from other conditions which result in similar phenotypes is considered, together with precipitants and confounders. Finally, the current multidimensional approach for the correct clinical recording of HE episodes is discussed.

It has been proposed that procedures which up-regulate mitochondrial biogenesis and autophagy by replacing damaged mitochondria with healthy ones, may prevent the development of several heart diseases. A member of serine and threonine kinases, AMPK, could play essential roles in the autophagy and/or mitophagy. AMPK is widely distributed in various cells, which might play diverse regulatory roles in different tissues and/or organs. In fact, changes in the kinase function of AMPK due to alteration of activity have been linked with diverse pathologies including cardiac disorders. AMPK can regulate mitochondrial biogenesis via PGC1α signaling and also improve oxidative mitochondrial metabolism through inhibition of mTOR pathway, which may also modulate the autophagy/mitophagy through ULK1 and/or TGF-β signaling. Therefore, the modulation of AMPK in autophagy/mitophagy pathway might be considered as a therapeutic tactic for several cardiac disorders. As kinases are amongst the most controllable proteins, in general, the design of small molecules targeting kinases might be an eye-catching avenue to modulate the cardiac function. Some analyses of the molecular biology underlying mitophagy suggests that nutraceuticals and/or drugs including specific AMPK modulator as well as physical exercise and/or dietary restriction that could modulate AMPK may be useful against several heart diseases. In particular, some nutraceutical regimens may have encouraging potential for controlling some of cardiac disorders.

Advanced heart failure (AHF) presents a complex landscape with challenges spanning diagnosis, management, and patient outcomes. In response, the integration of multimodality imaging techniques has emerged as a pivotal approach. This comprehensive review delves into the profound significance of these imaging strategies within AHF scenarios. Multimodality imaging, encompassing echocardiography, cardiac magnetic resonance imaging (CMR), and cardiac computed tomography (CCT), stands as a cornerstone in the care of patients with both short- and long-term mechanical support devices. These techniques facilitate precise device selection, placement, and vigilant monitoring, ensuring patient safety and optimal device functionality. In the context of orthotopic cardiac transplant (OTC), the role of multimodality imaging remains indispensable. Echocardiography offers invaluable insights into allograft function and potential complications. Advanced methods, like speckle tracking echocardiography (STE), empower the detection of acute cell rejection. CMR and CCT further enhance diagnostic precision, especially concerning allograft rejection and cardiac allograft vasculopathy. This comprehensive imaging approach goes beyond diagnosis, shaping treatment strategies and risk assessment. By harmonizing diverse imaging modalities, clinicians gain a panoramic understanding of each patient's unique condition, facilitating well-informed decisions. Thus, this review underscores the irreplaceable role of multimodality imaging in elevating patient outcomes, refining treatment precision, and propelling advancements in the evolving landscape of advanced heart failure management.

Background: the aim of this study was to assess acute changes on left atrial (LA) function a during a progressive exercise in patients with heart failure with mid-range ejection fraction (HFmrEF) in comparison to healthy controls (HS). Methods: twenty patients with established HFmrEF were compared with 10 HS, age-matched controls. All subiects performed a stepwise exercise test on cyclette. Echocardiography was performed at baseline, during submaximal effort, at peak of exercise, and after 5 minutes of recovery. Results: HS obtained an higher value of METs at peak exercise than HFmrEF (7.4 vs 5.6; between group p 0.002). Heart rate and systolic blood pressure presented a greater increase in the HS group than in HFmrEF (between-groups p 0.006 and p 0.003 respectively). In the HFmrEF group peak atrial longitudinal strain (PALS), and conduit strain were both increased at submaximal exercise (p<0.05 for both versus baseline) and remained constant at peak exercise. Peak atrial contraction strain (PACS) did not show significant changes during the exercise. In the control group PALS and PACS increased significantly at submaximal level (p<0.05 for both versus baseline) but PALS returned near baseline values at peak exercise; conduit strain decreased progressively during the exercise in HS. Stroke volume (SV) increased in both groups at submaximal exercise; at peak exercise SV remained constant in the HFmrEF while it decreased in controls (between-groups p 0.002). Conclusions: Patient with HFmrEF, show a proper increase of LA reservoir function during incremental exercise that contributes to maintain SV throughout the exercise.

Background: Inhibition of sodium-glucose co-transporter 2 (SGLT-2) has been shown to be beneficial in the treatment of diabetic and non-diabetic patients with heart failure with reduced ejection fraction (HFrEF). The underlying mechanisms are incompletely understood. The present prospective study investigates for the first time the effect of empagliflozin on various soluble markers of inflammation in HFrEF. Methods: We included 50 inpatients with HFrEF and diabetes mellitus type 2. Half of the patients received a therapy with the SGLT-2-inhibitor empagliflozin in addition to standard medication, the other half of the patients did not receive empagliflozin and were considered as control group. Quality of life, functional status and soluble immunological parameters in serum were assessed at baseline and after 3 months. Results: Baseline characteristics of both groups revealed no significant differences. Patients on empagliflozin demonstrated a significant improvement in the Minnesota living with heart failure questionnaire (baseline 44.2 ± 20.2 vs. 24 ± 17.7; p<0.001), in distance in the 6-minute walk test (baseline 343 ± 145 m vs. 450 ± 115 m; p<0.001) and in soluble interleukin-6 level (baseline 21.7 ± 21.8 pg/ml vs. 13.7 ± 15.8 pg/ml; p=0.008). There was no significant change of these or other parameters in the control group (p>0.05 each). Conclusions: The empagliflozin-induced improvement of quality of life and functional capacity in patients with HFrEF and type 2 diabetes mellitus is accompanied by a substantial reduction of interleukin-6 levels. Thus, antiinflammatory effects may contribute to the benefits of SGLT2-inhibitors in heart failure.

Introduction: The exponential growth of the SARS-CoV-2 virus transmission during the first months of 2020 has placed substantial pressure on health systems worldwide. The complications derived from the novel coronavirus disease (COVID-19) vary in due to comorbidities, sex and age, with more than 50% of the patients who require some level of intensive care developing acute respiratory distress syndrome (ARDS). Areas covered: Various complications caused by SARS-CoV-2 infection have been identified, the most lethal being the acute respiratory distress syndrome, caused most likely by the presence of severe immune cell response and the concomitant alveolus inflammation. The authors carried out an extensive and comprehensive literature review on SARS-CoV-2 infection, the clinical, pathological and radiological presentation as well as the current treatment strategies. Expert Opinion Elevation of inflammatory biomarkers is a common trend among seriously ill patients. The information available strongly suggests that in COVID-19 patients, their altered immune response, including a massive cytokine storm, is responsible for the further damage evidenced among ARDS patients. The increasingly high number of scientific articles and evidence available can only suggest that the individualization of each case is the norm, not all patients with acute respiratory failure due to COVID-19 meet the Berlin definition and therefore ARDS should be considered as a heterogeneous disease, with a wide range in the expression of its severity and clinical manifestations.

AbstractCadaver bone is possibly the most common transplant material used today. Common types of cadaver bone transplants are freeze-dried bone allografts and xenografts. Studies have shown that mineralized freeze-dried bone allografts have the same percentage of retained bone graft particles at different time points, indicating that these materials are never resorbed. However, it is commonly accepted by clinicians that these materials are resorbed and convert the graft site into normal bone. This histologic study was undertaken to determine the fate of mineralized freeze-dried bone allograft particles grafted into human extraction sockets. Materials and Methods:This study is a photographic, radiologic, and histological analysis of mineralized freeze-dried bone allograft healing in human sockets after mineralization at different time points. The mineralized freeze-dried bone allografts used for evaluation in this study were particulate bone graft materials in maxillary or mandibular extraction sockets. Patient selection was random, based on the following time periods: 6 months, 2 years, 5 years, 7 years, 10 years and 15 years. No block bone grafts were evaluated. Results:No resorption of cadaver bone graft particles was found at any time point. No osteoclasts were found in any of the histology at any time point. At different time points from 6 months through 15 years, mineralized freeze-dried bone allograft particles were found to be exfoliated out of the alveolar crest as a result of the formation of a hypervascular zone surrounding the grafted site. The embedded graft particles remain embedded in sclerotic bone until the particles reach the alveolar crest at which time the sclerotic bone and graft particles break up and are released into the gingiva. All histologic samples from 6 months to 15 years contained residual graft particles. The sclerotic bone formed around graft particles did not integrate to the graft particles or the implant surface. Conclusions:Mineralized freeze-dried bone allograft particles are not resorbed after mineralization. A hypervascular zone forms around the grafted site and exfoliates the bone graft particles into the gingiva. The mineralization process produces sclerotic bone which never remodels into normal bone. Sclerotic bone covers but does not integrate to the retained bone graft particles or implant surface resulting in a weakened structure with an increased likelihood of bone failure and implant loss.

Background: We aimed to evaluate whether baseline GLS and NT-proBNP and their changes after cardiac resynchronization therapy (CRT) can predict the long-term clinical outcomes and the echocardiographic-based response to CRT (defined by 15% relative reduction in left ventricular end-systolic volume). Methods: We enrolled 143 patients with stable, ischemic heart failure (HF) undergoing CRT-D implantation. NT-proBNP and echocardiogram were obtained before and 6 months after. The patients were followed-up (median: 58 months) for HF-related deaths and/or HF hospitalizations (primary endpoint) or HF-related deaths (secondary endpoint) Results: 84 patients achieved the primary and 53 the secondary endpoint, while 104 patients were considered as CRT-responders and 39 as non-responders. At baseline, event-free patients had higher absolute GLS values (p&lt;0.001) and lower NT-proBNP serum levels (p&lt;0001) than those achieving primary endpoint. A similar pattern was observed in favor of CRT-responders vs non-responders. In Cox regression analysis, lower baseline absolute GLS value (HR=0.77;95%CI, 0.51-1.91; p=0.002), higher baseline NT-proBNP levels (HR=1.55;95%CI, 1.43-2.01;p=0.002) and diabetes (HR=1.27;95%CI, 1.12-1.98;p=0.003) were associated with lower incidence of primary endpoint. Conclusions: In HF patients undergoing CRT-D, baseline GLS and NT-proBNP concentrations may serve as prognostic factors, while they may predict the echocardiographic-based response to CRT.

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.

Urban trees are often more sun- and wind-exposed than their forest-grown counterparts. These environmental differences can impact how many species grow – impacting trunk taper, crown spread, branch architecture, and other aspects of tree form. Given these differences, windthrow models derived from traditional forest production data sources may not be appropriate for urban forest management. Additionally, visual abnormalities historically labeled as “defects” in timber production may not have a significant impact on tree failure potential. In this study, we look at urban tree failures associated with Hurricane Irma in Tampa, Florida, USA. We used spatial analysis to determine if patterns of failure existed among our inventoried trees. We also looked at risk assessment data to determine which visual defects were the most common and the most likely to be associated with branch or whole-tree failure. Results indicate that there was no spatial pattern associated with the observed tree failures – trees failed or withstood the storm as individuals. While some defects like decay and dead wood were associated with increased tree failure, other defects like weak branch unions and poor branch architecture were less problematic.

This experimental study investigates the effect of scarf geometry in restoring the impact response of scarf patched 3 mm thick glass-fibre reinforced polymer (GFRP) matrix composite laminates. Traditional circular along with rounded rectangular scarf patch configurations considered as repair patches. Experimental measurements revealed that the temporal variations of force and energy response of the pristine specimen are close to that of circular repaired specimens. The predominant failure modes were witnessed only in repair patch which include the matrix cracking, fibre fracture, delamination and no discontinuity in adhesive interface was witnessed. When compared with the pristine samples, the top ply damage size of the of the circular repaired specimens is larger by 9.91 %, while that of the rounded rectangular repaired specimens is larger by 434.23 %. The results show that circular scarf repair is more suitable choice of repair approach under the condition of 37J low-velocity impact event even though the global force-time response is similar.

The present paper describes a study case of the failure investigation of Duplex stainless steel (UNS S31803) on the tube and tube sheet section of a shell and tube heat exchanger BEM TEMA type with seawater as the cooling medium. Although UNS S31803 offers high strength, high resistance to chloride-induced SCC, and high resistance to pitting attack in chloride environments, in this study case, the heat exchanger experienced some material degradation; 26 tubes were leaked and plugged on both sides, and scales plugged 76 tubes. The examination in this study case revealed the formation of biofilm inside the tubes, XRD examination revealed that the film contained aragonite (CaCO3), and by using microstructural examination on the inner surface of the tube, the austenite grains were preferentially attacked by crevice corrosion. In this case, the failure was caused by crevice corrosion, and crevice corrosion was enhanced by microbiological-induced corrosion (MIC). Recommendations to avoid similar failures are also suggested in this paper.

Objective: One of the major causes of cerebral ventricular shunt failure is proximal catheter occlusion. We describe a novel ventricular cerebrospinal fluid (CSF) flow replicating system that assesses pressure and flow responses to varied degrees of catheter occlusion. Methods: Ventricular catheter performance was assessed during conditions of partial and complete occlusion. The catheters were placed into a three-dimensionally printed phantom ventricular replicating system. Artificial CSF was pumped through the ventricular system at a constant rate of 1 ml/min to mimic CSF flow, with the proximal end of the catheter in the phantom ventricle. Pressure transducer and flow rate sensors were used to measure intra-phantom pressure, outflow pressure and CSF flow rates. The catheters were also inserted into silicone tubing and pressure was measured in the same manner for comparison with the phantom. Results: Pressure measured in the phantom ventricle did not change when the outflow of the ventricular catheter was partially occluded. However, the intraventricular phantom pressure significantly increased when the outflow catheter was 100% occluded. Flow through the catheter showed no significant difference in rate with any degree of partial occlusion of the catheter. At the distal end of the partially occluded catheters, there was less pressure compared with the nonoccluded catheters. This difference in pressure in partially occluded catheters correlated with the percentage of catheter hole occlusion. Conclusions: Our model mimics physiological dynamics of the CSF flow in partially and completely obstructed ventricular catheters. We found that partial occlusion of the catheter had no effect on CSF flow rate, but did reduce outflow pressure of the catheter.

In this paper, we aim to assess the electric current parameters and report the analysis of the associated degree of ventricular recovery during left ventricular assist device (LVAD) support. An assumption was made there is a linear relationship between ventricular recovery degree and the pump electric current pulsatility index (PI). The experimental study was carried out using the ViVitro Pulse Duplicator System with Sputnik 1 LVAD connected. Cardiac output (CO) and cardiac power output (CPO) were used as a measure of ventricular recovery degree. Different heart rates (HR) (59, 73, 86 bpm) and pump speeds (7600–8400 rpm in 200 rpm steps) were investigated. Ventricular stroke volumes in the range of 30–80 ml for each heart rate at certain pump speed were used. The obtained relationships of CO and CPO vs. PI was linear as the coefficients of determination for each regression curve were more than 0.8. CO vs. PI: R2=0.9218; 0.9271; 0.9172 and CPO vs. PI: R2=0.8517; 0.841; 0.8244 for HR=59 bpm; 73 bpm; 86 bpm, respectively. Study findings suggest that adequate interpretation of parameters could potentially serve as a valuable clinical tool to assess ventricular recovery based on LVAD infrastructure without requiring any special hemodynamic assessment.

The early failure of glaucoma surgery is mainly caused by an overly fibrosis at the subconjunctival space causing obliteration of the filtration bleb. Because fibrosis has a suspected basis of genetic predisposition, we have undertaken a prospective study to identify upregulated profibrotic genes in a population of glaucoma patients with signs of conjunctival fibrosis and early postoperative surgical failure. Clinical data of re-operated fibrosis patients, hyperfibrosis patients re-operated more than once in a short time, and control patients with no fibrosis were recorded and analyzed at each follow-up visit. Conjunctival-Tenon surgical specimens were obtained intraoperatively to evaluate the local expression of a panel of genes potentially associated with fibrosis. In order to correlate gene expression signature with protein levels, we quantified secreted proteins in primary cultures of fibroblasts from patients. Expression of VEGF-A, IL-8, C-MYC, and CDKN1A was induced in the conjunctiva of hyperfibrosis patients. VEGF-A and IL-8 protein levels were also increased in fibroblast supernatants. We propose that these proteins may act as biomarkers of conjunctival fibrosis in glaucoma patients undergoing filtering surgery. Molecular markers could be crucial for early detection of patients at high risk of failure of filtration surgery leading to more optimal and personalized treatments.

The fatigue crack growth rate (FCGR) of aluminium alloys under the combined influence of temperature and humidity remains a relatively unexplored area, receiving limited attention due to its intricate nature and challenges in predicting the combined impact of these factors. The challenge was to investigate and address the specific mechanisms and interactions between temperature and humidity, as in coastal environment conditions, on the FCGR of aluminium alloy. The present study conducts a comprehensive investigation on the combined influence of temperature and humidity on the FCGR of Al6082 alloy. The fatigue pre-cracked compact tension specimens were corroded for 7 days and then subjected to various temperature and humidity conditions in a thermal chamber for 3 days to simulate coastal environments. The obtained data were analysed to determine the influence of temperature and humidity on the FCGR of Al6082 alloy. An empirical model was also established to predict fatigue life cycle values under these environmental conditions precisely. The correlation between FCGR and fracture toughness models was also examined. The Al6082 alloy exhibits a 34% increase in the Paris constant C, indicating reduced FCGR resistance due to elevated temperature and humidity levels. At the same time, fatigue, corrosion, moisture-assisted crack propagation, and hydrogen embrittlement lead to a 27% decrease in threshold fracture toughness. The developed model exhibited accurate predictions for fatigue life cycles, and the correlation between fracture toughness and FCGR showed less than 10% error, indicating a strong relationship between these parameters.

Background: Acute heart failure (AHF) is a serious medical problem that necessitates hospitalisation and often results in death. Patients hospitalised to the emergency department (ED) should therefore receive an immediate diagnosis and treatment. Unfortunately, there is not yet a fast and accurate laboratory test for identifying AHF. The purpose of this research is to apply the principles of explainable artificial intelligence (XAI) to the analysis of hematological predictors for AHF. Methods: In this retrospective analysis, 425 patients with AHF and 430 healthy individuals served as assessments. Patients' demographic and hematological information was analyzed to determine AHF. Important risk variables for AHF diagnosis were identified using LASSO feature selection. To test the efficacy of the suggested prediction model (XGBoost), a 10-fold cross-validation procedure was implemented. The area under the receiver operating characteristic curve (AUC), F1 score, Brier score, and Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were all computed to evaluate the model's efficacy. Permutation-based analysis and SHAP, were used to assess the importance and influence of the model's incorporated risk factors. Results: White blood cell (WBC), monocytes, neutrophils, neutrophil-lymphocyte ratio (NLR), red cell distribution width-standard deviation (RDW-SD), RDW-coefficient of variation (RDW-CV), and platelet distribution width (PDW) values were significantly higher than the healthy group (p&lt;0.05). On the other hand, erythrocyte, hemoglobin, basophil, lymphocyte, mean platelet volume (MPV), platelet, hematocrit, mean erythrocyte hemoglobin (MCH) and procalcitonin (PCT) values were found to be significantly lower in AHF patients compared to healthy controls (p &lt;0.05). When XGBoost was used in conjunction with LASSO to estimate AHF, the resulting model had an AUC of 87.9%, an F1 score of 87.4%, a Brier score of 0.036, and an F1 score of 87.4%. PDW, age, RDW-SD, and PLT were identified as the most crucial risk factors in differentiating AHF. Conclusions: The XGBoost model demonstrated exceptional performance in accurately estimating Acute Heart Failure, and the application of Explainable Artificial Intelligence effectively provided intuitive explanations for the model's estimations. The suggested interpretable model holds potential for the identification of patients at high risk, thereby facilitating the optimization of treatment and planning for follow-up in cases of AHF.

The shear failure of surface methane capture borehole (SMCB) is the main cause of shortening life cycle of SMCB but lack of lithological analysis. In order to improve the stability of SMCB and improve efficient drainage period, it is of great significance to investigate the lithology performances for shear failure of SMCB. Based on the direct shear tests and geological method, the results shows that the shear displacement increases as the grain size decreases. Mechanical jump occurs at the lithological boundaries, which is mainly determined by the composition of rock specimens. The cohesion is the mainly possible reason for the step change of shear strength. Lithology with high quartz and low clay may effectively improve shear strength and failure resistance. Boreholes drilled into the weaker siltstone and mudstone sections may potentially experience preferential damage due to the larger shear displacement and shear strength. Protective measures at these sections may improve the stability of the borehole casing. The probing data where it was found that boreholes closure validated the prediction.

Background: Congestive heart failure is the inability to pump blood throughout the body which causes the walls to be unable to pump adequately. Purpose: This study aimed to ascertain the effect of a contrast bath with a 30 º elevation on the reduction of edema in congestive heart failure patients at Ulin General Hospital, Banjarmasin. Methods: The design of this study was quasi-experimental with an unequal control group design. The population is patients with congestive heart failure, and the sample used is successive sampling. 34 respondents were divided into two groups, 17 respondents in the intervention group and 17 in the control group. Results: The Mann-Whitney result value P = 0.027 (P < 0.05) represented a significant reduction in Bath contrast edema with 30º feet elevation in the intervention group and control group patients with congestive heart failure. Conclusion: Based on the results of this study, it is expected to be able to apply contrast showers with an elevation of 30 º in nursing services to reduce the degree of edema in congestive heart failure patients.

Coronary microvascular dysfunction (CMD) is a clinical entity linked with various risk factors that significantly affect cardiac morbidity and mortality. Hypertension, one of the most important, causes both functional and structural alterations in the microvasculature, promoting the occurrence and progression of microvascular angina. Endothelial dysfunction and capillary rarefaction play the most significant role in the development of CMD among patients with hypertension. CMD is also related to several hypertension-related morphological and functional changes in the myocardium in the subclinical and early clinical stages, including left ventricular hypertrophy, interstitial myocardial fibrosis, and diastolic dysfunction. This indicates the fact that CMD, especially if associated with hypertension, is a subclinical marker of end-organ damage and heart failure, particularly the one with preserved ejection fraction. This is why it is important to search for microvascular angina in every patient with hypertension and chest pain not associated with obstructive coronary artery disease. Several highly sensitive and specific non-invasive and invasive diagnostic modalities have been developed to evaluate the presence and severity of CMD, but also to investigate additional complications that can affect further prognosis, especially among those with hypertensive heart disease. Although various pharmacological and interventional treatments demonstrated certain clinical effects, integrated diagnostic and therapeutic algorithms are necessary to reduce the burden of this emerging condition.

The kidney and the heart work together in balancing the body circulation and although their physiology is based on strict inter dependence, their performance fulfills different aims. While the heart can rapidly increase its own oxygen consumption to comply with the wide changes in metabolic demand linked to body function, the kidney physiology is primarily designed to maintain a stable metabolic rate and has limited capacity to cope with any steep increase in renal metabolism. In the kidneys the glomerular population filters a large amount of blood and the tubular system has been programmed to reabsorb 99% of filtrate by reabsorbing sodium together with other filtered substances including all glucose molecules. Glucose reabsorption involves the sodium-glucose cotransporters SGLT2 and SGLT1 on the apical membrane in the proximal tubular section; it also enhances bicarbonate formation so as to preserve the acid-base balance. The complex work of reabsorption in the kidney is the main factor in renal oxygen consumption; analysis of renal glucose transport in disease states is providing better understanding of the renal physiology changes that occur when clinical conditions alter the neurohormonal response leading to an increase in glomerular filtration pressure. In this circumstance glomerular hyperfiltration occurs, imposing a higher metabolic demand on kidney physiology and causing progressive renal impairment. Albumin urination is the warning signal of renal engagement over-exertion and most frequently heralds heart failure development, regardless of disease etiology. The review analyzes the mechanisms linked to renal oxygen consumption, focusing on sodium-glucose management.

The entry and exit method is a simple and practical method to determine the critical slip surface of slope. However, it has the drawback of sacrificing computational efficiency to improve search accuracy. To solve this problem, this paper proposes an improved entry and exit method to search for the critical slip surface. Based on the random fields generated by using Karhunen–Loève expansion method, the simplified Bishop’s method combined with the improved entry and exit method is used to determine the critical slip surface and its corresponding minimum factor of safety. Then, the failure probability is calculated by conducting Monte Carlo simulation. Two examples are reanalyzed to verify the accuracy and efficiency of the proposed method. Meaningful comparisons are made to demonstrate the calculating accuracy and calculating efficiency of the improved entry and exit method in searching for the minimum safety factor of slope, based on which the effect of the reduced searching range on slope reliability was explored. The results indicate that the proposed method provides a practical tool for evaluating the reliability of slopes in spatially variable soils. It can greatly improve the computational efficiency in relatively high-computational accuracy of slope reliability analysis.

The formability and failure behavior of TRIP steel blanks were investigated through various stress states. The forming limit diagram (FLD) at fracture is constructed both experimentally and numerically. Numerical studies are performed to evaluate the applicability of different damage criteria in predicting the FLD as well as complex cross-die deep drawing process. The fracture surface and numerical results revealed that the material failed in a different mode for different strain path. Therefore, Tresca model which is based on shear stress accurately predicted the conditions where shear had the profound effect on the damage initiation, whereas Situ localized necking criterion was able to calculate the conditions which localization was dominant.

The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in a significant surge of critically ill patients and an unprecedented demand on intensive care services. The rapidly evolving understanding of pathogenesis, limited disease specific evidence and demand-resource imbalances have posed significant challenges for intensive care clinicians. COVID-19 is a complex multisystem inflammatory vasculopathy with a significant mortality implication for those admitted to intensive care. Institutional strategic preparation and meticulous intensive care support are essential to maximising outcomes during the pandemic. The significant mortality variation observed between institutions and internationally, despite a single aetiology and uniform presentation, highlights the potential influence of management strategies on outcome. Given that optimal organ support and adjunctive therapies for COVID-19 have not yet been well defined by trial-based outcomes, strategies are predicated on existing literature and experiential learning. This review outlines the relevant pathophysiology and management strategies for critically ill patients with COVID-19, and shares some of the collective learning accumulated in a high volume Severe Respiratory Failure centre in London.

: The ichthyofauna of Lake Tanganyika consists of 12 families of fish of which five belong to Siluriformes (catfishes). Studies on siluriforms and their parasites in this lake are very fragmentary. The present study was carried out to help fill the knowledge gap on the monogeneans parasitizing the siluriform fishes of Lake Tanganyika in general and more particularly Clarias gariepinus. The gills of a specimen of Clarias gariepinus (Clariidae) were examined for ectoparasites. We identified the monogenean Gyrodactylus transvaalensis (Gyrodactylidae). This is the first time this parasite was found infecting gills. We are the first to observe a large spine in the male copulatory organ of this species, and to provide measurements of its genital spines; this completes the description of the male copulatory organ which is important in standard monogenean identification. This is the first monogenean species reported on C. gariepinus at Lake Tanganyika and the third known species on a representative of Siluriformes of this lake. It brings the total number of species of Gyrodactylus recorded in Lake Tanganyika to four. Knowing that other locations where this species has been reported are geographically remote from Lake Tanganyika, we propose a “failure to diverge” phenomenon for G. transvaalensis.

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.

Diagnosis and prognosis of failures for aircrafts’ integrity are some of the most important regular functionalities in complex and safety-critical aircraft structures. Further, development of failure diagnostic tools such as Non-Destructive Testing (NDT) techniques, in particular, for aircraft composite materials, has been seen as a subject of intensive research over the last decades. The need for diagnostic and prognostic tools for composite materials in aircraft applications rises and draws increasing attention. Yet, there is still an ongoing need for developing new failure diagnostic tools to respond to the rapid industrial development and complex machine design. Such tools will ease the early detection and isolation of developing defects and the prediction of damages propagation; thus allowing for early implementation of preventive maintenance and serve as a countermeasure to the potential of catastrophic failure. In this paper, following a short introductory summary and definitions, this paper provides a brief literature review of recent research on failure diagnosis of composite materials with an emphasis on the use of NDT techniques in aerospace industry. In addition to this, within a some of significant NDT application extents, prognosis of composites is also briefly discussed.

Bayesian analysis for masked data under competing risk frameworks is studied for the purpose of assessing the impact of covariates on the hazard functions when the failure time is exactly observed for some subjects but only known to lie in an interval of time for the remaining subjects. Such data, known as partly interval-censored data, usually result from periodic inspection. Dirichlet and Gamma processes are assumed as priors for masking probabilities and baseline hazards. The Markov Chain Monte Carlo (MCMC) technique is employed for the implementation of the Bayesian approach. The effectiveness of the proposed model is tested through numerical studies, including simulated and real data sets.

Heart failure (HF) diagnosis, phenotyping, prognosis, and treatment decisions are all based on the left ventricular ejection fraction (EF). Heart failure with mid-range EF (HFmrEF) is a third EF category for heart failure with an EF between 40 and 49 percent. Comparatively, heart failure with preserved EF or reduced EF has been largely unexplored. 10–25% of patients with HF have HFmrEF. Although HFmrEF has an intermediate clinical profile, it is more similar to HF with reduced EF, particularly because these patients have a high incidence of ischaemic heart disease. Heart failure with preserved EF has a lower risk of cardiovascular events than heart failure with reduced EF, which is milder. HFmrEF and HF with preserved EF patients have a similar or higher risk of non-cardiovascular adverse events than patients with HF with reduced EF. There is still a great deal of mystery surrounding HFmrEF. The purpose of this review is to describe the major pathophysiology of HFmrEF and its similarities and differences with the other two types of EF. It is the purpose of this paper to present a comprehensive overview of the currently available evidence in support of the pathophysiology of patients with HFmrEF. Further investigation of the pathophysiology, treatment, and prognosis of this condition will be needed in the future in order to better understand it.

Heart failure is a leading cause of death among people worldwide. The cost of treatment can be prohibitive, and early prediction of heart failure would reduce treatment costs to patients and hospitals. Improved prediction of readmission would also be of great help hospital, allowing them to better manage their treatment programs and budgets. This systematic review aims to summarize recent studies of predictive analytics models that have been constructed to predict heart failure and readmission. Some of these models use a statistical approach and others a machine learning approach. Electronic patient health records, including demography, physical and clinical values, and laboratory findings are used to design and build predictive models. Predictive analytics with good performance have become essential for clinicians and specialists. Choosing a suitable machine learning algorithm and data preprocessing technique will improve predictive model performance, including data imputation and class imbalance.

PURPOSE: The aim of this study was to identify the incidence of early mechanical failure in the first post-surgical year in patients who had undergone spinal surgery, and to assess the related risk factors. METHODS: Retrospective observational study of a prognostic cohort was conducted at an orthopaedic hospital, examining all patients with spine degenerative disease who consecutively underwent arthrodesis surgery between March 2018 and March 2019. The incidence of postoperative mechanical failure during the first year was calculated as primary outcome; the time between the date of the implant surgery and diagnosis of the mechanical failure was calculated as secondary outcome. RESULTS: A total of 237 patients were identified for statistical analysis. The median age of the group of patients was 47 years (IQR of 44), and 66.6% were female. The incidence of mechanical failure in the first postoperative year was 5.1% overall with 12 events and the median time between surgery and the need for revision surgery was 5 months (IQR=7.75). ASA score (OR= 2,39; p=0.134), duration of the surgical procedure (OR=1,27; p=0,006) and inability to walk at discharge (OR=7,86; p=0,072) were independent risk of factor associated with the mechanical failure. CONCLUSION: Higher ASA score and longer duration of surgery are risk factors for mechanical failure in the first year in patients who had undergone spinal surgery and must be carefully considered when planning spinal surgery. During hospitalization, recovery of ambulation must be encouraged to prevent mechanical failure. All these factors are useful in identifying patients with a closer follow-up is needed.

Left ventricular (LV) remodeling is a dynamic process which is characterized by abnormal LV wall thickness and altered myocardial geometry, and it is considered as a negative prognostic factor in both heart failure with reduced eject fraction (HFrEF) and heart failure with preserved eject fraction (HFpEF). Hypertension, type 2 diabetes (T2D) and obesity are strongly correlated with the development and the progression of LV remodeling, LV hypertrophy and LV systolic and/or diastolic dysfunction. Indeed, the beneficial impact of exercise training on primary and secondary prevention of cardiovascular disease (CVD) has been well-established. Recent studies highlight that exercise training enhances functional capacity, muscle strength and endurance, cardiac function and cardiac-related biomarkers, among patients with established coronary artery disease (CAD) or HF, thus improving substantially their cardiovascular prognosis, survival rates and needs for rehospitalization. Therefore, in this review article, we discuss the evidence of LV remodeling in patients with cardiometabolic risk factors, such as hypertension, T2D, obesity, and also highlight the current studies evaluating the effect of exercise training on LV remodeling in these patients.

Though there has been a decline in the number of new cases of viral hepatitis-induced acute liver failure in Europe and the United States of America, viral hepatitis still remains the leading cause of acute liver failure in Asia-Pacific and South America. However, the epidemiology of viral-hepatitis-induced acute liver failure in sub-Saharan Africa-the world epicenter of viral hepatitis-is unclear. The aim of this review was to collate data on the incidence, prevalence, specific etiologic agents, features/diagnosis, treatment and prognosis of viral-induced acute liver failure in sub-Saharan Africa. One hundred and forty-seven cases of viral-induced acute liver failure were recorded in 11 studies conducted in six countries between 1981-2020. Etiological agents were: Hepatitis viruses A, B, C, and E, as well as Adenovirus, Enterovirus, Parvovirus, Herpes Simplex Virus (HSV) and EBV. HAV was the most frequent in paediatric subjects: (11/16) 69% and (19/30) 63%. HBV was the only etiological agent in the study that only included adults. HEV (genotype 2 in one study) contracted amidst hepatitis E outbreaks was the most commonly reported cause of ALF in pregnant women. Treatment was mainly supportive, and liver transplantation reported only in South Africa. Where reported, case fatality rates were high. In conclusion, viral-hepatitis induced acute liver failure is largely understudied in sub-Saharan Africa. The few available data are consistent with literature from the other parts of the world regarding aetiologic agents. Liver transplantation is not available in most sub-Saharan African countries, and short-term case fatality rates of individuals with acute liver failure could outstrip current rates from the other world regions.

In the development of the safety-critical systems, it is important to perform Failure Modes and Effects Analysis (FMEA) process to identify potential failures. However, traditional FMEA activities tend to be considered difficult and time-consuming tasks. To compensate for the difficulty of the FMEA task, various types of tools are used to increase the quality and the effectiveness of the FMEA reports. This paper explains an Automatic FMEA tool which integrates the Model-based Design (MBD), FMEA, and Simulated Fault Injection techniques in a single environment. The Automatic FMEA tool has the following advantages compared to the existing FMEA analysis tool. First, the Automatic FMEA tool automatically generates FMEA reports compared to the traditional spreadsheet-based FMEA tools. Second, the Automatic FMEA tool analyzes the causality between the failure modes and the failure effects by performing model-based fault injection simulation. In order to demonstrate the applicability of the Automatic FMEA, we used the electronic fuel injection system (EFI) Simulink model. The results of the Automatic FMEA were compared to that of the legacy FMEA.

Background. The type-2 sodium-glucose cotransporters inhibitors (SGLT2i) are a new relevant therapeutic option for patients affected by chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate, in a real-world population from a single center, the feasibility of introducing SGLT2i and their interaction with other recommended drug classes. Methods. We evaluated the consecutive patients affected by chronic heart failure (CHF) since January 2022. At baseline clinical visit the therapy taken by the patients as well as that prescribed were accurately collected. During a 6-12 month follow-up the the changes in concomitant therapy were analyzed. Results. At baseline, among 350 patients evaluated, only 17 (5%) were already taking SGLT2i, 13 with HFrEF, 2 with CHF with mild reduced (HFmrEF) and 2 with preserved ejection fraction (HFpEF). After baseline evaluation, SGLT2i were prescribed to 220 (63%) of all the patients enrolled, among whom 178 (84%) of HFrEF patients, 25 (42%) of HFmrEF and 17 (22%) of HFpEF. After follow-up, SGLT2i therapy was highly tolerated and it was associated with a significant increased prescription of sacubitril/valsartan and a reduced use of diuretics. Finally, a significant improvement in functional status and left ventricular systolic function after SGLT2i therapy was observed. Conclusions. In this single center “real world” study, SGLT2i were prescribed in HFrEF patients most of all already in therapy with the other classes of drugs currently recommended for their treatment. Moreover, a further optimization in prescribed ther-apy was observed during a short term follow-up. These data further support the use of this thera-peutic approach in routine clinical practice.

Purpose: Kidney Transplant Recipients (KTRs) tend to develop infections with characteristic epidemiology, presentation and outcome. While infective endocarditis (IE) is among such complications in KTRs, literature is scarce. We describe the presentation, epidemiology, and factors associated with IE in KTRs. Methods: We performed a retrospective case/control study which included patients from two centers. First episodes of definite or possible IE (Duke criteria), in adult KTRs from January 2007 to December 2018 were included, as well as two controls per case, and followed until December 31 2019. Clinical, biological, and microbiological data and the outcome were collected. Survival was studied using the Kaplan-Meier method. Finally, we searched for factors associated with the onset of IE in KTRs by the comparison of cases and controls. Results: Seventeen cases and 34 controls were included. IE was diagnosed after a mean delay of 78 months after KT, mostly on native valves of the left heart only. Pathogens of digestive origin were most frequently involved (six Enterococcus spp, three Streptococcus gallolyticus and one Escherichia coli), followed by Staphylococci (three cases of S. aureus and S. epidermidis each). Among the risk factors evaluated only age was significantly associated with the occurrence of IE in our study (63.8 years for cases vs. 55.6 years for controls, P=0.03) Patient and death-censored graft survival were greatly diminished five years after IE compared to controls being 50.3% vs. 80.6% (p<0.003) and 29.7% vs. 87.5% (p<0.002), respectively. Conclusion: IE in KTRs is a disease that carries significant risks both for the survival of the patient and the transplant.