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.

Background. There are scant data about the effectiveness of high flow nasal cannula (HFNC) oxygen therapy in patients hospitalized with severe acute respiratory failure (ARF) in non-intensive medical wards, particularly regarding the effect on arterial oxygenation compared to conventional oxygen therapy (COT) and non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP). Methods. In a retrospective observational study, oxygenation parameters were measured before and immediately after HFNC initiation in 37 consecutive patients hospitalized in a geriatric ward in 2017. Results. HFNC was used as escalation therapy for untreatable hypoxia after failure of NIV/CPAP (n=18) or COT (n=19). Twenty-two patients died, 2 were transferred to the intensive care unit, while 13 were discharged alive. A “do not intubate” status was identified in 17 of the 22 deceased patients. Partial pressure of oxygen (pO2, p< 0.0001), oxygen saturation (SO2, p< 0.0001), pO2/fraction of inspired oxygen ratio (p=0.004) and peripheral SO2 measured by pulse oximetry (p< 0.0001) significantly increased soon after HFNC application. Oxygenation improvements were greater after escalation from NIV/CPAP and in patients discharged alive. Conclusion. HFNC significantly improved oxygenation in severe ARF after failure of COT or NIV/CPAP and may be particularly suitable for older patients hospitalized in non-intensive medical wards.

Anesthetic management for pregnant suffering from airway pathology poses unique challenges. The presence of bilateral vocal cord granuloma adds further complexity to the management, as it can potentially cause airway compromise and respiratory distress. This case presents a pregnant patient with bilateral vocal cord granuloma who underwent anesthesia using high-flow nasal cannula (HFNC) oxygenation and oxygen reserve index (ORi) monitoring. A 33-year-old pregnant woman, who had undergone intubation six month ago, experienced hoarseness and was ultimately diagnosed with bilateral granuloma. Due to the significant airway obstruction, neither intubation nor ventilation was feasible, thereby requiring a surgical intervention. Before the surgical removal, the patient’s oxygenation was ensured using HFNC oxygenation. After confirming sufficient oxygenation of the patient with ORi of 0.38, the operation commenced and as it lasted approximately 3 minutes, the patient was able to tolerate the brief period without additional oxygen supply. Post-surgical excision, mask bagging and HFNC oxygenation was resumed, driving ORi to 0.39, then the operation was resumed. Throughout the procedure, SpO2 remained above 98. The combination of HFNC and ORi ensured adequate oxygenation and allowed for early detection of hypoxemia during the procedure. This approach may be a good option for managing granuloma.

Background: During the pandemic, Emergency departments were overcrowded with critically ill patients and confronted ethical dilemmas to assign respiratory support to them due to scarce resources. Quick tools to evaluate patients at admission were needed; many scores were used but inaccurate to predict outcomes. The Rox Index is an easy and fast score that reflects the respiratory status in acute respiratory failure patients, this score could predict the outcome of covid 19 patients. Hypothesis: The 24-hour difference in the Rox Index discriminate accurately the mortality and needs for mechanical ventilation of patients with covid-19. Methods: Study design: Prospective analytic study. Population: 204 Patients admitted to the emergency department from May to August 2020. Data were collected from the clinical records. The Rox Index was calculated at admission and 24h later, the difference was used to establish the outcome, a logistic regression model adjusting for age, sex, presence of comorbidities and disease severity to build and perform ROC analysis. Results: Difference in respiratory ROX Index between admission and 24h is a good predictor for death AUC 0.92 and for mechanic ventilation AUC: 0.75. Each decrease in one unit of the difference at 24h had an Odds Ratio for death risk: 1.48 (95%CI: 1.31-1.67) and for mechanic ventilation: 1.16 (95%IC: 1.1-1.23). Conclusion: The 24-hour variation of Rox Index has good predictive value and allows healthcare professionals to identify which patients will benefit from invasive treatment, especially in low resource settings where emergency physicians deal with survival.

Many people in the USA have lost their lives or become addicted to opioids via prescription opioids given for chronic pain. The chronic pain epidemic has emerged due to a convergence of factors, including the medicalization of pain as well as injuries happening in the workplace, in the home, or during recreation. Opioid prescriptions rose precipitously from the late 1990’s through to approximately 2020, and despite public awareness, still are increasing. This review examines literature on integrative approaches to chronic pain as delineated by pain type. The review is organized by the most common causes of chronic pain, and randomized controlled trials, meta-analyses and systematic reviews are extracted for each cause of chronic pain. Several promising interventions may alleviate chronic pain of some causes, and some interventions may work across pain causes. Lowering inflammation through dietary or lifestyle regimens may be a general way of reducing pain. Pain can be alleviated through several adjunctive and integrative treatment approaches, which may serve to lower the need for opioid medication.

All severe cases of SARS-CoV-2 infections are characterized by a high risk of disease progression towards ARDS, leading to bad outcome. Respiratory symptoms in COVID-19 patients often do not correspond to disease’s worsening. A dysregulated host response to the large viral load could play a key role in the disease progression. In our sample median age was 74 years (72-75) and 54% were men. Median period of hospitalization was 9 days. Firstly, we observed an asynchronous trend of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) in 764 selected among 963 patients who were consecutively recruited in two hospitals (Cannizzaro, S. Marco) in Catania, Italy. NLR values in deceased patients showed an increase from baseline over time. By contrast, CRP tended to fall from baseline to median day of hospitalization in all four subgroups, but steeply increased at the end of hospitalization only in ICU-admitted patients. Then we evaluated the relationships between NLR and CRP as continuous variables with PaO2/FiO2 ratio (P/F). Finally, we made mediation and moderation analyses to determine the link between inflammation (CRP), immune system (neutrophils and lymphocytes) and respiratory failure (P/F). CRP, neutrophils and P/F are linked in the same pathogenetic chain leading to respiratory failure.

Hypertension is a global public health challenge, with a high prevalence across various regions and significant implications for cardiovascular risk. This article reviews the effectiveness of herbal medicine as a potential therapeutic approach for hypertension, offering an alternative or complementary solution to conventional pharmacological treatments. It highlights several natural agents that have demonstrated efficacy in lowering systolic blood pressure (SBP) in clinical and meta-analytical studies. The methodology involved a systematic review of articles that discuss herbal therapeutics for hypertension, focusing on their efficacy compared to placebo and standard treatments. The findings suggest that certain nutraceuticals, such as garlic, hawthorn, and CoQ10, can significantly reduce SBP, presenting a viable option for managing hypertension. This review underscores the need for further research to validate these findings and optimize herbal treatment strategies, potentially expanding the use of these natural products in clinical practice. The article aims to increase awareness among medical professionals and patients about the benefits and applications of herbal medicines in treating hypertension.

The aging populations observed across numerous countries worldwide necessitate a thorough exploration of interventions aimed at promoting healthy aging. As individuals age, they undergo significant physiological changes that impact their functional capacity and often necessitate increased reliance on external support systems. Enhancing the autonomy and well-being of elderly individuals emerges as a critical imperative, serving not only individual interests but also broader societal goals. This review investigates various interventions designed to optimize the health and independence of aging populations, offering insights into effective strategies for promoting healthy aging and mitigating the societal burdens associated with an aging demographic.

Antidepressants are among the most used medications in the US, with significant deleterious effects on people’s well-being. At any given time, depression impacts approximately 1 in 10 Americans, causing wide and broad societal costs. Interest is developing for non-pharmacological treatments and preventative measures. We summarize the literature on non-invasive dietary and lifestyle approaches for treating depression, including recent work with the psychedelic treatment of depression. This review aims to inform future research and treatment programs for depression. This review provides an evidentiary summary of integrative therapeutic approaches for depression.

On the 9th March 2020, the first patient with COVID-19 was admitted to ICU in the Royal Gwent Hospital, Newport, Wales. We prospectively recorded the rate of ICU admissions of 52 patients with COVID-19 over 60 days, focusing on the epidemiology of ethnicity and deprivation. Patients were 65% (34 of 52) male and had a median (IQR) age of 55 (48-62) years. Prevalent comorbidities included obesity (52%); diabetes (33%), and asthma (23%). COVID-19 hospital and ICU inpatient numbers peaked on days 23 and 39, respectively – a lag of 16 days. The ICU mortality rate was 33% (17 of 52). Black, Asian and Minority Ethnics (BAME) population represented 35% of ICU COVID-19 admissions (18 of 52) and 35% of deaths (6 of 17). Within the BAME group, 72% (13 of 18) were found to reside in geographical areas representing the 20% most deprived in Wales, versus 27% of Caucasians (9 of 33). Less than 5% of the population within the hospital catchment area are of BAME descent, yet they represent a disproportionately high proportion of patients with ICU admission and mortality suffering from COVID-19. The interplay between ethnicity and deprivation, which is complex, may be a factor in our findings. This in turn could be related to an increased prevalence of co-morbidities; higher community exposure; or genetic polymorphisms.

Background: Vasoactive Intestinal Peptide (VIP) is known to bind to and protect the Alveolar Type II cell by blocking replication of the SARS-CoV-2 virus, upregulating surfactant production, blocking apoptosis, and blocking cytokine effects. RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) has been granted Fast Track Designation and is currently in phase 2/3 placebo-controlled trials. FDA has granted Emergency Use IND and Expanded Access Protocol approval for the use of RLF-100 in patients whose comorbidities render them ineligible for inclusion in the ongoing pivotal trial. Methods: This report describes the first 6 patients with Acute Respiratory Failure in Critical COVID-19, enrolled under Emergency Use IND were treated with three successive 12-hour infusions of intravenous Aviptadil at 50/100/150 pmol/kg/hr, while continuing to receive maximal ICU care. Results: Median patient follow-up time is 14 days. So far, all treated patients have survived. Improved radiographic appearance of typical “ground glass” COVID-19 features to varying degrees is seen in all patients within 72 hours. Improvement in blood oxygenation is seen in all patients, with complete remission from respiratory failure in 4 of 6 patients. An average 56% reduction in inflammatory markers was seen, together with a median 4 point reduction in the NIAID Ordinal Scale. 2/6 patients were discharged from the hospital and 1 patient was downgraded to the general medicine floor. Comment: The short term survival of 6/6 patients with respiratory failure in the setting of COVID-19 and major comorbidity is the most dramatic response ever seen with an antiviral agent. Improvement in radiographic appearance, oxygenation requirement, and inflammatory markers is consistent with in vitro evidence of direct anti-viral effect.

Coronavirus disease 2019 (COVID-19) is caused by infection with the 2019 novel coronavirus 2 (2019-nCoV, now referred to as SARS-CoV-2). COVID-19 has become a global pandemic since its outbreak at the end of Dec 2019. COVID-19 could lead to severe acute respiratory disease, especially to those who have reduced immunity. Binding of the viral Spike protein (S) to its receptor ACE2 (Angiotensin Converting Enzyme 2) on the surface of target cells has been proven to be key for virus entry and infection. Although ACE2 expression in the respiratory system is necessary for pneumonia infection by SARS-CoV-2, the regulation of ACE2 gene expression remains poorly investigated, especially for patients that are in pre-pathological conditions. Here, by analyzing The Gene Expression Omnibus (GEO) database, we investigated the expression regulation of ACE2 in various kinds of primary epithelial cells from the respiratory system after varies of respiratory viruses infection such as influenza A virus (IFV), respiratory syncytial virus (RSV) and human rhinovirus (hRV). Our analyses reveal that infection of multiple kinds of respiratory viruses or influenza vaccines greatly increased ACE2 expression, suggesting that respiratory viruses infection could represent a high risk factor for developing COVID-19. We also found that the regulatory effect of influenza A virus on ACE2 expression is associated with activation of the interferon beta-induced pathway and viral RNA-activated host response. Together, our data provide a theoretical framework for clinical classification for SARS-CoV-2 infection susceptibility and could be used for future prevention and therapy treatment for COVID-19.

The persistence of symptoms following COVID-19 infection represents a significant challenge in healthcare management. During the outbreak, tele-rehabilitation emerged as a new tool to support healthcare structures in providing rehabilitation services. This study assessed the effectiveness and the feasibility of a 3-week home-based motor and respiratory rehabilitation program for long COVID-19 individuals after traditional rehabilitation. Twenty-three patients completed the program and underwent functional tests at different time points (i.e. baseline, after hospital discharge, and after tele-rehabilitation). Motor function was evaluated using the instrumented Six-Minutes Walking Test (i6MWT), with monitored heart rate and oxygen saturation. Conversely, respiratory function was measured via forced vital capacity (FVC) and maximal voluntary ventilation (MVV) tests. Significant improvements (p &lt; 0.05) in motor and respiratory function were observed throughout the intervention, including an 18.3% increase in walked distance from the baseline. The findings suggest that a home-based tele-rehabilitation can enhance motor and respiratory function in post-COVID patients. Despite limitations such as sample size and lack of control group, the positive outcomes seem to support the feasibility of the proposed tele-rehabilitation program in managing long COVID symptoms and promoting functional recovery. Further research is needed to validate these findings and explore tele-rehabilitation’s potential in broader patient populations.

Background. In a cannot ventilate cannot intubate situation, careful preoxygenation with high FiO₂ allowing subsequent apneic oxygenation can be life-saving. The best position for an oxygen supply line within the human airway at which oxygen insufflation is more effective than standard preoxygenation with a face mask, or comparably effective as intratracheal insufflation, is unknown. Methods. In this experimental study, we compared effectiveness of preoxygenation by placing an oxygen cannula at the nose entrance, through the nose at the soft palatine, or at the base of tongue; as control we used ambient air. We connected a fully preoxygenated test lung on one side to an oximeter with a flow rate of 200ml/min simulating oxygen consumption of a normal adult, and on the other side to the trachea of an anatomically correctly shaped airway manikin over a 20 min observation period five times for each cannula placement in random order. Results. Oxygen percentage in the test lung dropped from 100% in all groups to 53±1% in the ambient air control group, to 87±2% in the nasal cannula group, to 96±2% in the soft palatine group, while it remained at 99±1% in the base of tongue group (p=0.003 for soft palatine vs base of tongue; and p<0.001 between all other groups). Conclusions. When simulating apneic oxygenation in a preoxygenated manikin, oxygen insufflation at the base of tongue kept oxygen percentage at baseline values of 99% demonstrating a complete block for ambient air flowing into the manikin’s airway. Oxygen insufflation at the soft palatine or insufflation via nasal cannula were less effective in regard of this effect.

Background and Objectives: Most individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are asymptomatic or have mild symptoms of COVID-19, which usually resolve after few days. Regardless of symptoms, infected people can transmit the virus to others especially on the first days of infection. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) is used to confirm SARS-CoV-2 infection; some individuals show persistent PCR-positivity after recovering from COVID-19. In this study, 12 individuals who showed persistence of COVID-19 symptoms and of SARS-CoV-2 PCR-positivity were followed-up. Methods: nasopharyngeal samples were collected for SARS-CoV-2 detection by RT-qPCR; clinical and epidemiological data were analyzed. Results: that persistence of SARS-CoV-2 PCR positivity was associated with duration of symptoms (r_s 0.81338), which varied between one and 49 days, with 75% of the individuals reporting symptoms for more than two weeks; 83.33% of cases remained positive after two weeks of onset of symptoms, despite decreases in viral load. Conclusion: neither RT-qPCR test nor a symptom-based approach alone are sufficient to evaluate discontinuation of patient isolation; other factors such as viral loads and symptom severity should also be considered. Additional studies are needed to understand how RT-PCR-positivity is related to symptoms and the risk of viral transmission, and to better support isolation guidelines.

Nasal cavity is a primary checkpoint for the invasion of several respiratory pathogens. Numerous pathogens including SARS-CoV-2, S. pneumonia, S. aureus, etc., adhere to the nasal epithelium or mucus to invade and trigger an infection. IgA serves as the first line of defense against foreign antigens and pathogens. They exhibit cross-reactivity against a diverse variety of antigens through immune exclusion, which intercepts the invasion of pathogens through the mucosal lining. Advances in intranasal immunization technology underscore the elevated neutralizing IgA levels at local and distal mucosa in contrast to the parenteral vaccines. This review highlights the adjuvants that induce IgA class switching and the challenges of maintaining nominal IgA levels at the mucosal surface. Finally, the review features the paradigm-shifting of conventional immunization techniques to IgA-inducing vaccines to enhance protection against homologous and heterologous pathogens.

The rapid convergence of Artificial General Intelligence (AGI), autonomous drones, and applied robotics presents a transformative opportunity for many sectors. However, this advancement also raises critical ethical and existential questions, particularly in warfare. This paper explores the concept of entropy as a metaphor for the potential disorder introduced by these increasingly complex technologies. We examine the risks of AGI surpassing human control in conflict situations, where autonomous decision-making could have disastrous consequences. We then analyze autonomous drones, scrutinizing their impact on warfare tactics and the ethical dilemmas surrounding independent, real-time decision-making. Finally, we investigate applied robotics in military operations, focusing on the delicate balance between enhanced capabilities and the potential for uncontrollable systems. Through a multidisciplinary lens, drawing on technology ethics, military strategy, and AI safety, this paper utilizes the concept of entropy to highlight the need for caution in developing these technologies. We propose a scientifically grounded and ethically sound framework to guide policymakers, technologists, and ethicists in navigating the path between innovation and global stability. This framework concludes with recommendations for responsible development and deployment strategies that can mitigate the risks associated with these powerful tools.

Nebulized thrombolysis offers locally targeted therapy with potentially lower bleeding risk than systemic administration for coronavirus disease 2019 (COVID-19) respiratory failure. In a proof-of-concept safety study, adult patients with COVID-19-induced respiratory failure and a <300mmHg PaO2/FiO2 (P/F) ratio, requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care during the first two UK COVID-19 waves. Matched historical controls (MHC; n=18) were used in C1. Safety co-primary endpoints were treatment-related bleeds and fibrinogen reduction to <1.0–1.5 g/L. A dose escalation strategy for improved efficacy with the least safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40–60 mg rt-PA per day for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeding events (one severe and three mild) in three patients were considered treatment-related. No significant fibrinogen reductions were reported. Greater improvement in mean P/F ratio from baseline to end of study was observed in C1 compared with MHC [C1; 154 to 299 vs MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in P/F ratio was observed in NIRS patients [NIRS; 126 to 240 vs IMV; 120 to 188) and they required fewer treatment days (NIRS; 7.86 vs IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, showing a trend of improved oxygenation and faster recovery in patients with acute COVID-19-induced respiratory failure requiring respiratory support; this effect was more pronounced in the NIRS group. Further investigation is required to study the potential of this novel treatment approach.

The increasing demand for higher power in rocket launchers is driving the development of higher power nozzles, achieved essentially by increasing the expansion ratio. However, this can lead to flow separation and resulting unsteady, asymmetrical forces, called side loads, which can limit the life of both the nozzle itself and other engine components. If this problem can be overcome, engine performance can be significantly increased. Therefore, various separation control methods have been proposed, but none have been fully implemented to date due to the uncertainties associated with modeling and predicting the flow phenomena. A numerical study of high area ratio rocket engine is presented to analyze the aeroelastic performance of the structure under the condition of flow separation. The finite volume method, the 2nd order upwind scheme and the extended wall function are used to analyze the flow inside the rocket nozzle and the transition of the Free Shock Separation (FSS) to Restricted Shock Separation (RSS) separation pattern ) to be discussed in detail. Since the location of the flow separation point depends heavily on the flow.

Background: Telemonitoring systems in cardiology have shown potential in improving chronic cardiovascular disease (CVD) management. This study aims to evaluate the impact of telemonitoring, mainly through mobile applications, on patient outcomes such as self-care, blood pressure control, quality of life, and hospitalization. Methods: We systematically reviewed studies assessing telemonitoring methods for patients with chronic CVD. The analysis included studies from various geographic regions and healthcare settings, focusing on qualitative outcomes without performing a meta-analysis. Results: Telemonitoring was found to aid in maintaining blood pressure and significantly enhance self-care abilities. Improvements in quality of life were observed in some studies, though results varied. Most studies indicated telemonitoring could effectively manage blood pressure and reduce hypertension-related complications. However, the heterogeneity of interventions and outcomes measured across trials posed challenges for a comprehensive meta-analysis. Conclusions: Integrating telemonitoring systems into routine care can significantly improve disease management and patient outcomes for chronic CVD patients. Future research should standardize telemonitoring interventions and outcome measures, conduct long-term studies, and evaluate the cost-effectiveness of these systems. Greater blindness in future randomized controlled trials and more studies on atrial fibrillation are also necessary. Significant potential exists for telemonitoring to improve patient outcomes and assist in managing chronic illnesses.

Some COVID-19 patients develop interstitial pneumonia that can evolve into Acute Respiratory Distress Syndrome (ARDS). This is accompanied by an inflammatory cytokine storm. SarS-CoV has proteins capable of promoting cytokine storm, especially in patients with comorbidities, including obesity. Since there is currently no resolutive therapy for ARDS and given the scientific literature regarding the use of adenosine, its application has been hypothesized. Adenosine through its receptors is able to inhibit the acute inflammatory process, increase the protection capacity of the epithelial barrier and reduce the damage due to an overactivation of the immune system, such as in cytokine storms. These features are known in ischemia / reperfusion models and could also be exploited in acute lung injury, with hypoxia. In light of these hypotheses, for compassionate use, a COVID-19 patient, with unresponsive respiratory failure, was treated with adenosine. The results showed a rapid and clear improvement in clinical conditions, with the negative effect of detection of SarS-CoV2.

Patients who survived critical COVID-19 frequently reported post-acute sequelae of COVID-19 (PASC) such as psychosomatic and neurocognitive health problems. The goal of this study was to identify clinical risk factors and other predictors for such long-term consequences in severely ill COVID-19 patients. Adult COVID-19 intensive care unit (ICU) survivors from August 2020 to May 2021 were enrolled. A broad range of clinical, laboratory and chest computed tomography (CT) data was collected during ICU stay. The association between ICU predictors and psychosomatic, respiratory and neurocognitive assessments 12 months after ICU discharge was analyzed using univariate regression analysis. In 17 patients (mean age 58.9 ± 11.4 years), laboratory markers (CRP, lymphocytes, hemoglobin), ICU severity (SOFA, SAPS II, need for mechanical ventilation), complications (ARDS), and lung CT data (ground-glass opacity) were promising predictors of depressive and anxiety symptoms, fatigue, and sleep problems. Recovery of psychosomatic health such as fatigue, depression and anxiety correlated with lower levels of inflammation and high hemoglobin levels. ARDS, mechanical ventilation and worse SOFA and SAPS II scores were further risk factors for depressive and anxiety symptoms. Our study identified novel associations such as pulmonary ground-glass opacity being positively associated with depression, anxiety, fatigue, and insomnia levels.

The Circular Bioeconomy (CBE) combines the concepts of bioeconomy and circular economy. As an alternative concept to the current fossil-based, linear economy, it de-scribes an economy based on the efficient valorization of biomass. It is regional in nature and aims to improve sustainability. An analysis of the transition process, by identifying its success criteria and assessing its impacts through the modelling of technology-specific scenarios is necessary to ensure that CBE concepts are sustainable. However, a compre-hensive consideration of regional influences on both is lacking. Based on extensive literature research and an expert survey, we (i) present a compre-hensive catalog of CBE success criteria and discuss their region-specific character and (ii) develop a methodology based on evaluation matrices that enable to match CBE technolo-gies with regions. The matrices support the evaluation of technological and regional characteristics influencing the successful CBE implementation. The results show that the success criteria "biomass resources", "technological", and "social" are perceived as highly important, and that most of the success criteria are both region- and technology-specific, highlighting the relevance of developing matrices to match them. We describe such matrices indicatively for the two broadest and most im-portant success criteria clusters “social acceptance” and “biomass supply chain”. With this, we substantiate the regional nature of CBE and raise the awareness on the importance of considering regional conditions in CBE transition processes. Furthermore, we provide practical guidance on how regional conditions can be reflected in the selection of technologies, e.g. in regional CBE technology scenarios.

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.

Since the discovery of the Coronavirus disease 2019 (COVID-19) outbreak, a vast majority of studies have been carried out that confirmed the worst outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with preexisting health conditions, including diabetes, obesity, hypertension, cancer, and cardiovascular diseases. Likewise, diabetes itself is one of the leading causes of global public health concerns that impose a heavy global burden on public health as well as socio-economic development. Both diabetes and SARS-CoV-2 infection have their independent ability to induce the pathogenesis and severity of multi-system organ dysfunction, while the co-existence of these two culprits can accelerate the pathophysiology and magnify the severity of the diseases. However, the exact pathophysiology of multi-system organ failure in diabetic patients after SARS-CoV-2 infection is still obscure. This review summarized the organ-specific possible molecular mechanisms of SARS-CoV-2 and diabetes-induced pathophysiology of several diseases of multiple organs, including the lungs, heart, kidney, brain, eyes, gastrointestinal system, and bones, and subsequent manifestation of multi-system organ failure.

The emergence of drug-resistant mycobacteria has rendered many clinical drugs and regimens ineffective, imposing significant economic and healthcare burden on individuals and society. Repurposing drugs intended for treating other diseases is a time-saving, cost-effective, and efficient approach for identifying excellent anti-mycobacterial candidates or lead compounds. This study is the first to demonstrate that rupatadine (RTD), a drug used to treat allergic rhinitis, possesses excellent activity against mycobacteria without detectable resistance, particularly Mycobacterium tuberculosis and Mycobacterium marinum, with a minimal inhibitory concentration as low as 3.13 µg/mL. Furthermore, RTD exhibited moderate activity against nonreplicating M. tuberculosis with the minimal inhibitory concentrations lower than drugs targeting the cell wall, suggesting that RTD has the great potential to be modified and used for the treatment of nonreplicating M. tuberculosis. Additionally, RTD exhibits partial synergistic effects when combined with clofazimine, pretomanid, and TB47 against M. tuberculosis, providing the theoretical foundation for the development of treatment regimens. Transcriptomic profiling leads us to speculate that eight essential genes may be the targets of RTD or may be closely associated with the mycobacterial resistance to RTD. In summary, RTD may be a promising hit for further anti-mycobacterial drug or regimen optimization, especially in case of nonreplicating mycobacteria.

We revisit a 2023 JAMA-published analysis of data from patients admitted for either COVID-19 or influenza to U.S. Veterans Administration (VA) hospitals in the fall/winter of 2022-2023. We note that baseline characteristics between the cohorts were similar, and the difference in vaccination rates was minimal, even after propensity score weighting. Had the vaccines been even minimally effective, significant differences in vaccination percentages would be expected. These findings call into question any efficacy claims associated with either the COVID-19 or influenza vaccines. Furthermore, the lack of efficacy of the influenza vaccines in reducing hospitalization is consistent with an earlier detailed study that found the same lack of efficacy, further validating the current result. This suggests that comparing vaccination rates between those hospitalized for different vaccine-preventable diseases can serve as a practical method for validating the vaccine efficacy claims of different vaccines.

With the emergence of COVID-19 we are confronted with a new clinical picture of acute respiratory distress syndrome in the intensive care unit. In the majority of patients, the respiratory mechanics are very different from the “normal” ARDS patient. We measured transpulmonary pressure and dead space ventilation to assess the effects of high and low PEEP levels on lung compliance and ventilation-perfusion mismatching. Advanced respiratory mechanics were assessed in 14 patients. Compared to ARDS patients, lung compliance was relatively high (61 ± 5 mL/cmH₂O). COVID-19 patients had high dead space ventilation and gas exchange impairment (Bohr 52 ± 3%; Enghoff modification 67 ± 2%; ventilatory ratio 2.24 ± 0.23). we show that higher PEEP levels decrease lung compliance and in most cases increase dead space ventilation, indicating that high PEEP levels probably cause hyperinflation in patients with COVID-19. We suggest using prone position for an extended period of time, and apply lower PEEP levels as much as possible.

This paper presents MADS (Multi-Agents for Data Science), an innovative and simple open-source multi-agent framework designed for systemic pipeline execution in applied supervised machine learning. By leveraging the capabilities of multi-agent systems (MAS), we introduce a universal approach to optimize and streamline machine learning pipelines. Our framework highlights the differences between various types of agents, such as reinforcement learning (RL) agents and large language model (LLM) agents, and their distinct contributions to the process. While we currently employ LLM agents to automate and enhance machine learning tasks, we acknowledge the potential of incorporating RL agents in future iterations to further improve performance and adaptability. The primary objective is to enhance the efficiency, scalability, and adaptability of supervised learning applications across various domains. This integration addresses the complexity and manual effort typically associated with machine learning workflows, paving the way for more automated, robust, and scalable solutions. Our approach demonstrates significant improvements in task automation, reduced human intervention, and enhanced model performance. The MADS framework, which will soon be available as an open-source implementation, represents a pivotal contribution to the field of machine learning, promising to facilitate broader adoption and collaborative advancement.

Abstract: Laryngoscopy for tracheal intubation has been developed for many decades. Among various conventional laryngoscopes, videolaryngoscopes (VL) have been applied in different patient populations, including difficult airways. The safety and effectiveness of VL have been repeatedly studied in both normal and difficult airways. The superiority of VL then has been observed and is advocated as the standard of care. In contrast to laryngoscopy, the development of video-assisted intubating stylet (VS, also named as styletubation) has been noticed two dec-ades ago. Since then, sporadic clinical experiences of use have appeared in literature. In this re-view article, we presented our vast use experiences of the styletubation (more than 55,000 pa-tients since 2016). We found this technique is swift (the time to intubate: from 3 s to 10 s), smooth (first-attempt success rate: 100%), safe (no airway complications), and easy (high subjective satis-faction and fast learning curve for the novice trainees) in both normal and difficult airway sce-narios. We therefore propose styletubation technique can be feasibly applied as universal rou-tine use for tracheal intubation.

There are limited proven therapies for the treatment of COVID-19. Vitamin C’s antioxidant, anti-inflammatory and immunomodulating effects, make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19, supporting anti-inflammatory treatment. This literature review focuses on vitamin C deficiency in respiratory infections including COVID-19; the mechanism of action in infectious disease and adrenal function supporting the anti-inflammatory actions of glucocorticosteroids: its role in preventing and treating colds and pneumonia and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8g/d) may reduce incidence and duration of respiratory infections and intravenous vitamin C (2-24g/d) has been shown to reduce mortality, Intensive Care Unit and hospital stays, time on mechanical ventilation in severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and frequency of vitamin C deficiency in respiratory infections it may be worthwhile testing patients’ vitamin C status and treating accordingly with intravenous use within ICUs and orally with doses between 2 and 8g/day in hospitalised and infected persons.

The current Covid-19 pandemic has hugely disrupted the delivery of routine and established medical care. Patients can develop a wide range of clinical signs and symptoms from a cough and fever to severe respiratory failure. There is an ongoing argument on a concise investigative pathway to ensure the safety of all healthcare workers. The stethoscope can help with any clinical respiratory assessment but the risk of cross infection is high. Computer tomography should not be routinely performed. There is a potential place for lung ultrasound but outcomes are not yet determined.

The severe acquired respiratory coronavirus–2 (SARS–CoV-2) infection has initiated both acute and chronic COVID–19 disease between 2020 and 2023, currently evolving with other homologous prior coronavirus strains of the Nidoviridae order, which encompasses other prevalent alpha/ beta coronaviruses, but also the Middle East Respiratory Syndrome (MERS-CoV) and SARS-CoV-1, with recent SARS–CoV–2 variants, increasing demands for effective immunogens and therapeutic approaches that will reduce global disease burden and further infection from SARS–CoV-2 affected individuals that may experience post acute sequelae (PASC) or “Long COVID”. Following a worldwide programme of prophylactic vaccination, there is still a dilemma in the efforts to find prophylactic and early therapeutic approaches that would treat novel SARS-CoV-2 variants and prevent future epidemics or pandemics within host human and animal populations, where zoonotic or cross species transfer naturally occurs. Concerns about viral immune escape intersect at a specific point; a gained evolutionary ability of several viruses to co–infect and compete against previous scientific advances since 1796 that remain undetected or asymptomatic during the early stages of infection progressing to symptomatic and severe disease via the double methylation of the 5' end of eukaryotic DNA or RNA-based viral genomes, the 7-MeGpppA2’-O-Me cap, and its double methylation capping process is performed by the activated viral 2’ - O - Methyltransferase (MTase) enzyme, a complex of two viral non-structural proteins (NSPs) joined together through an activation process (NSP10/16) and by N7-Methyltransferase (N7-MTase/NSP14), respectively. Moreover, it was discovered that polymorphic viruses translate NSP1, which prevents the activation of various Pattern Recognition Receptors (PRRs), and consequently, detection of Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs) alike. NSP1 also silences important interferon-encoding genes (INGs) and interferon-stimulated genes (ISGs), is signalled in a paracrine manner to neighbouring cells, and that induces the apoptosis of host cells, inducing an effect of “trace erase” effect and making the viral infection as immunologically “invisible” as possible during the initial, key stages of viral replication and distribution, all such mechanisms occurring independently of the viruses in cause. Another important viral NSP is NSP14, as it plays two functional roles that are independent of each other; to produce new viral genetic material for the purpose of maintaining the validity of the viral genome as well, and not just transfer a methyl group to the 5’ end of the viral genome. Other viral NSPs share a role with NSP1, 10, 14 and 16 in directly suppressing the activation of PRRs and ISGs, and all such viral proteins help the virus in its process of self-camouflaging against first- and second-line immunity, thereby often severely impacting the quality of the produced adaptive immune responses. The outcome of all such phenomena is the sharp decrease in the host Type I and Type III interferons' (IFNs) rate of synthesis by the host cells, that would usually occur and affect homeostatic cellular pathways, resulting in further viral replication and induced apoptosis. Nonetheless, effects of microbial immune evasion during the development of other viral or carcinogenic pathologies are not widely known. In short, polymorphic viruses developed a proportionate evolutionary response against developed adaptive immune responses, by currently relying on gaps mostly situated in the natural immune system in their process of molecular self-camouflaging. Scientists developed numerous approaches of early treatment that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration whilst filtering for the most appropriate solutions. For example, the administration of recombinant human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can simulate intracellular infection and stimulate cellular activity in a timely manner, training the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Another example could involve the treatment of natural and adaptive lymphocytes with a low dose of IFNs I and possibly III, prior to their insertion into the host lymphatic system, possibly alongside additional recruitment of plasmacytoid dendritic cells (pDCs) as further interferon “factories”, all with the purpose of early infection management. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. It is until the scientific community realises this potentially crucial aspect that large proportions of the world population will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently, monkeypox and possibly avian flu. Of note, it has been indicated that IFN I and / or III display significant immunising, early therapeutic and clinical disease onset-attenuating effects for many other microbial evoked diseases, as well as for a number of oncological diseases.

Medication non-adherence remains a substantial obstacle in asthma care, prompting the exploration of novel therapeutic modalities that prioritize rapid symptom relief, anti-inflammatory activity and facilitate patients’ compliance. This task is well served by a new form of therapy - inhaled triple-combination medications ICS/LABA/LAMA (inhaled glucocorticosteroid/long-acting beta2-agonist/long-acting muscarinic antagonist). The integration of three medications within a singular inhalation device culminates in the reduction of the effective dose of the principal therapeutic agent for asthma management, namely, ICS. This consolidation yields a dual benefit of minimizing the likelihood of adverse effects typically linked with ICS while concurrently optimizing bronchodilator efficacy. The accumulated evidence suggests that adding LAMA to a medium- or high-dose ICS/LABA results in a decrease of asthma exacerbations compared to medium- or high-dose ICS/LABA alone, accompanied by sustained enhancements in lung function parameters. We propose in adult patients experiencing suboptimal asthma control despite medium/high-dose ICS/LABA treatment - regardless of adherence to GINA-recommended strategies, such as MART therapy as a first-line approach or alternative second-line strategies - the preferred course for intensifying asthma therapy involves the addition of a LAMA, ideally in the form of SITT.

Rapid development and deployment of vaccines greatly reduced mortality and morbidity during the COVID-19 pandemic. The most widely used COVID-19 vaccines approved by national regulatory authorities require intramuscular administration. SARS-CoV-2 initially infects the upper respiratory tract where the infection can be eliminated with little or no symptoms by an effective immune response. Failure to eliminate SARS-CoV-2 in the upper respiratory tract results in lower respiratory tract infections that can lead to severe disease and death. Presently used intramuscularly administered COVID-19 vaccines are effective in reducing severe disease and mortality but are not entirely able to prevent asymptomatic and mild infections as well as person to person transmission of the virus. Individual and population differences also influence susceptibility to infection and the propensity to develop severe disease. This article provides a perspective on the nature and the mode of delivery COVID-19 vaccines that can optimize protective immunity in the upper respiratory tract to reduce infections and virus transmission as well as severe disease.

Introduction: The viral respiratory disorder known as severe acute respiratory syndrome (SARS) is caused by the SARS-associated coronavirus. End of May 2021, there have been over 170 million reported cases and more than 3.53 million deaths worldwide. In the field of cardiovascular performance, the shock index (SI) is a simple and widely used formula that measures the physiological response prior to systemic hypotension. It is obtained by dividing the heart rate by the systolic blood pressure. Another parameter, the modified shock index (MSI), is defined as the ratio of heart rate to mean arterial pressure (MAP). Methods: In this retrospective study, we examined the data of COVID-19 patients who were admitted to the ICU between June 1st, 2020, and January 31st, 2021. The patient details were collected from the Medical Records Department (MRD) in a tertiary care center. A case-recorded proforma was used to record the patient information, which was then analyzed using SPSS software. Results: The mean age of the patients was 67 years, consisting of 64 males (68.9%) and 29 females (31.1%). The standard deviation was calculated as 13.557. Among the patients, the minimum age recorded was 28, while the maximum age was 97. Patients with known CAD (Coronary Artery Disease) had a higher mortality rate among comorbidities. The p-value for Shock Index and Mortality Status was 0.205 (with an alpha value greater than 0.05), indicating no significant association. However, the modified shock index (MSI) showed a significant association with mortality status. The Pearson chi-square value for MSI and Mortality Status was 4.19, with a p-value of 0.041 (with an alpha value less than 0.05). These results suggest that there is a higher risk of mortality for patients with a Modified Shock Index of less than 0.7 or greater than 1.3. The MSI Odds ratio was found to be 4.500, indicating that such patients have a 4.5 times higher risk of mortality compared to others. Conclusion: In conclusion, our study found that there is no significant association between the Shock Index (SI) and mortality, as the p-value was greater than 0.05. However, the Modified Shock Index (MSI) showed a significant association with mortality status, with a p-value less than 0.05. This suggests that patients with a Modified Shock Index less than 0.7 or greater than 1.3 are at a higher risk of mortality. It is important to consider these findings when assessing the prognosis and potential interventions for COVID-19 patients.

Extracorporeal membrane oxygenation (ECMO) support for respiratory failure in the intensive care unit continues to have an expanded role in select patients. While acute respiratory distress syndrome remains the most common indication, ECMO may be used in other causes of refractory hypoxemia and/or hypercapnia. The most common configuration is veno-venous (V-V) ECMO, however in specific cases of refractory hypoxemia or right ventricular failure, some patients may benefit from veno-pulmonary (V-P) ECMO or veno-venoarterial (V-VA) ECMO. Patient selection and extracorporeal circuit management are essential to successful outcomes. This narrative review explores the physiology of ECMO, indications and contraindications, ventilator management, extracorporeal circuit management, troubleshooting hypoxemia, complications, and ECMO weaning in patients with respiratory failure. As the footprint of ECMO continues to expand it is essential that clinicians understand the underlying physiology and management of these complex patients.

Idiopathic pulmonary fibrosis, a chronic and fatal condition with no effective cure, is a challenging disease within the group of interstitial lung diseases. The pathogenic mechanisms of this disease are still not fully understood. In this context, the research on miRNAs, which are small non-coding RNAs that regulate messenger RNAs, is of utmost importance. These miRNAs, released into the circulation outside the cell through exosomes, play a crucial role in the pathogenic pathways and mechanisms involved in IPF development. The analysis of miRNAs in the serum/plasma of IPF patients has opened up new possibilities in the search for biomarkers. This review focuses on circulating miRNAs validated by real-time PCR in IPF and the evidence reported about the pulmonary fibrotic process.

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.

Nasal nitric oxide (nNO) is a gas synthesized by the inducible and constitutive NO synthase enzyme in the airway cells of the nasal mucosa. Like lung nitric oxide, it is thought to be associated with airway inflammation in various respiratory diseases in children. The aim of our review was to investigate the current state of use of nasal nitric oxide measurement in children. A comprehensive search was conducted using the Web of Science and PubMed databases specifically targeting publications in the English language, with the following keywords: nasal NO, children, allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). We describe the use of nNO in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD), and cystic fibrosis (CF) based on the latest literature. CONCLUSION: nNO is a noninvasive, clinically applicable test for use in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, PCD and CF. It can be used as a complementary method in the diagnosis of these respiratory diseases and as a monitoring method for the treatment of allergic rhinitis, acute and chronic rhinosinusitis.

Nasal high-frequency oscillatory ventilation (nHFOV) has emerged as an effective initial and rescue noninvasive respiratory support mode for preterm infants with respiratory distress syndrome (RDS). Multiple noninvasive respiratory support modes are currently available in Romania, but little is known about nHFOV use in Romanian neonatal intensive care units (NICUs). We aimed to identify the usage extent and clinical application of nHFOV in Romania. A structured web-based questionnaire was designed to find the rate of nHFOV use and knowledge of this new method of noninvasive respiratory support in Romanian level III NICUs. The questionnaire was addressed to the leaders of all level III Romanian NICUs. Using multiple-choice, open-ended, and yes/no questions, we collected information on the NICU’s size, noninvasive respiratory support modes used, nHFOV use, indications, settings, nasal interfaces, secondary effects, and equipment used. Descriptive statistics and comparisons were performed using IBM SPSS Statistics 26.0. A total of 21/23 (91.3%) leaders from level III NICUs (median [IQR] number of beds of 10 [10-17.5]) responded to the survey. The most frequently used noninvasive ventilation modes were CPAP mode on mechanical ventilators (76.2%), followed by NIPPV (76.2%), heated, humidified high flow nasal cannula (HHHFNC) (61.9%), and nHFOV (11/21 units; 52.4%); 5/11 units reported frequent nHFOV use (in 2 or more newborns/month) in both term and preterm infants. The main indications reported for nHFOV use were CPAP failure (90.9%), hypercapnia (81.8%), and bronchopulmonary dysplasia (72.7%). 10/11 units reported setting a mean airway pressure (MAP) equal to the CPAP level plus 1-2 cmH₂O on rescue nHFOV after CPAP failure. Both dedicated equipment (45.5%) and hybrid ventilators (63.6%) were used for nHFOV delivery, with face/nasal masks and short binasal prongs being the most commonly used nasal interfaces (90.9% and 72.7%, respectively). Air leaks at the interface level (90.9%), thick secretions (81.8%), and airway obstruction (63.6%) were the most frequently mentioned adverse effects of nHFOV; none of the units mentioned pneumothorax as an adverse effect. Only 3 of the NICUs had a written protocol for nHFOV use. Initial, minimum, and maximum amplitude and initial and minimum MAP settings used were significantly higher with hybrid ventilators as compared to dedicated equipment (p<0.05). Most units not yet using nHFOV cited lack of equipment, experience, training, or insufficient information and evidence for the clinical use and outcome of nHFOV use in neonates as the main reasons for not implementing this noninvasive respiratory mode. Our survey showed that nHFOV is already used in more than half of the Romanian level III NICUs to support term and preterm infants with respiratory distress despite a lack of consensus regarding indications and settings during nHFOV. A need for training for nHFOV use was identified, and efforts are needed at the national level to develop courses and training sessions, including using simulation workshops, to offer more information on optimal nHFOV use in clinical practice.

The coronavirus disease 2019 (COVID-19), instigated by the zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), rapidly transformed from an outbreak in Wuhan, China, into a widespread global pandemic. A significant post-infection condition, known as ‘long- COVID’, emerges in a substantial subset of patients, manifesting with a constellation of over 200 reported symptoms that span multiple organ systems. This condition, also known as 'post-acute sequelae of SARS-CoV-2 infection' (PASC), presents a perplexing clinical picture with far-reaching implications, often persisting long after the acute phase. While initial research focused on the immediate pulmonary impact of the virus, the recognition of COVID-19 as a multiorgan disruptor has unveiled a gamut of protracted and severe health issues. This review provides a summary of the primary effects of long COVID on the cardiovascular, nervous, and respiratory systems. It also delves into the mechanisms underlying these impacts and underscores the critical need for a comprehensive understanding of long COVID's pathogenesis.

On March 11, 2020, coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO). This review focuses on where the body mass index (BMI) value can be used as a tool to evaluate the risk of development and/or aggravation of this disease. Databases were used to search studies published up to April 18, 2020. In total, 4285 articles and other scientific literature were found, and twelve articles were included in this systematic review. The mean BMI value of severe COVID-19 patients ranged from 24.5 to 33.4 kg/m², versus 22.0 to 24.3 kg/m² for non-severe patients Articles using the terms obesity or overweight, without indicating the BMI value, in these patients were common, but this is not useful as the nutritional status, when not defined by this index, is confusing due to the classification being different in the West compared to among,, Asian and Korean criteria-based adults. Furthermore, the use of BMI is important during this pandemic, as it should be applied to nutritional support therapy during hospitalization of infected patients, as well as being considered in the home confinement population.

Extracellular vesicles (EVs) hold enormous potential in the diagnosis and treatment of diseases, benefit from their roles in intercellular signaling, as well as their plentiful presence and stability in body fluids. However, conventional EV isolation methods are labor-intensive, and harvest EVs with low purity and compromised recovery. In addition, the drawbacks, such as limited sensitivity and specificity of traditional EV analysis methods hinder the application of EVs in clinical use. Therefore, it is urgent to develop effective and standardized methods for isolating and detecting EVs. Microfluidics technology is a powerful and rapidly developing technology that has been introduced as a potential solution for the above bottlenecks. It holds the advantages of high integration, short analysis time, low consumption of samples and reagents. In this review, we summarize the traditional techniques alongside microfluidic-based methodologies for the isolation and detection of EVs. We emphasize the separation advantages of microfluidic technology in enhancing EV capture efficiency and precise targeting, while summarizing its analytical role in targeted detection and discussing the significance of EV detection in the tumor microenvironment, providing a direction for achieving automated and high-throughput EV detection in clinical samples.

The paper presents a proposal for an in-house mathematical model of a liquid flat-plate solar collector. The proposed model is a one-dimensional distributed parameter model enabling simulations of the collector operation under arbitrarily variable boundary conditions. The model is based on the solution of energy balance equations for all components of the collector. The formulated differential equations are solved iteratively using an implicit difference scheme. In order to obtain a stable numerical solution, it is necessary to use appropriate steps of the time and spatial division. These were found by comparing the results obtained from the model with the results of the analytical solution available in the literature for the transient state, which constitutes the novelty of the present study. The accuracy of the results obtained from the model was verified experimentally by comparing the measured and the calculated history of the fluid temperature at the outlet of the collector. The calculation of the collector time constant is proposed in the paper as an example of the model practical application. The results of the time constant calculation were compared with the values obtained experimentally on the test stand. This is another novelty of the presented research. The analysed collector instantaneous efficiency was then calculated for selected outdoor conditions. The presented mathematical model can also be used to verify the correctness of the collector operation. Comparing, on an ongoing basis, the measured and the calculated values of the fluid temperature at the collector outlet, conclusions can be drawn about the process of solar glass fouling or glycol gelling. The model's simplicity and the low computational demands enable such comparisons in an online mode.

According to many research groups, high glucose induces over production of superoxide anions, and reactive oxygen species (ROS) in general is the link between high glucose levels and the toxicities seen at cellular levels. Respiratory complex anomalies could lead to the production of ROS. Calcium [Ca2+], at physiological levels serves as a second messenger in many physiological functions. Accordingly, mitochondrial calcium [Ca2+]m overload leads to ROS production which could be lethal to the mitochondria through various mechanisms. The F1F0-ATPase (ATP syn-thase or complex V) is the enzyme that is responsible for catalyzing the final step of oxidative phosphorylation. It does so by coupling the translocation of protons in the mitochondrial in-termembrane space and shuttling them to the mitochondrial matrix for ATP synthesis to take place. Mitochondrial complex V T8993G mutation specifically blocks the translocation of protons across the intermembrane space thereby blocking ATP synthesis leading to Neuropathy, Ataxia and Retinitis Pigmentosa Syndromes (NARP). This study seeks to explore the possibility of [Ca2+]m overload mediating the pathological roles of high glucose in defective respiratory chain mediated mitochondrial stress. The NARP cybrids are the in vitro experimental models for the cells with F1FO-ATPase defects, these cells harbor 98% of mtDNA T8993G mutation. Their coun-terparts 143B osteosarcoma cell lines are the parental cell lines used for comparisons. We uncov-ered that, NARP cells mediated and enhanced the death of the cells (apoptosis) when incubated with hydrogen peroxide (H2O2) and high glucose respectively as depicted by the MTT assay of cell viability. Furthermore, using the fluorescence probe-coupled laser scanning confocal imag-ing microscopy, NARP cells significantly enabled mitochondrial reactive oxygen species (mROS) formation and enhanced the depolarization of the mitochondrial membrane potential (ΔΨm). Elucidating the mechanisms of sugar enhanced toxicity on mitochondria would help in the fu-ture to alleviate the symptoms of patients associated with (NARP) syndromes.

The COVID-19 pandemic has impacted the healthcare system across the globe, leading to more than 6.9 million deaths in the past four years. Cardiac Arrest is a terminal event with associated significantly high morbidity and mortality across age groups. Multiple clinical parameters, organ dysfunction, and chronic co-morbid conditions impact mortality in COVID-19 patients with heart failure. In this retrospective, administrative dataset-based study on 148899 patients admitted to the hospital with COVID-19 and heart failure diagnosis, we reported 6703 cardiac arrests and 5783 mortality. We have used ICD 10 codes to identify the diagnosis. The primary objective of the study is to find the predictors of Cardiac Arrest among patients admitted to hospitals with COVID-19 and heart failure. Secondary objective is to calculate the percentage of cardiac Arrest and mortality across the various age groups and the correlation of hours on the mechanical ventilator and mortality. Study results have shown that the use of a mechanical ventilator has the strongest co-correlation with cardiac Arrest with an odd ratio of 14.4, followed by septic shock with an odd ratio of 5.6, tension pneumothorax with an odd ratio of 4.9 preceding the acute renal failure with an odd ratio of 2.4 and sepsis 2.3. Complete heart block had an odd ratio of 1.9, followed by ESRD with a ratio of 1.6, acute pulmonary embolism with an odd ratio of 1.5, and Type 2 MI with an odd ratio of 1.49. Chronic co-morbid condition of DM had an odd ratio of 1.3, followed by Atrial fibrillation with an odd ratio of 1.1. These results and findings emphasized that multi-organ failure has a huge impact on cardiac Arrest among COVID-19 patients with heart failure.

Background: Several reports indicate that long stay at home for online schools due to the COVID-19 pandemic changed the normal physical activity and body weight of school-age students. Previous studies revealed that almost 50% of school students complained of increased or decreased more than 3 kg of weight due to lower physical activity. This study aims to provide insight about the Body Mass Index (BMI) among school students during COVID-19 pandemic. Methods: A retrospective matched-longitudinal study was conducted in 2022 based on previous data about BMI-for-age percentile in school-age students aged 6 to 18 years. These data were collected the year before and during COVID-19 pandemic (2019-2021). Results: All the included students were Arabic (N = 53,580) and were not diagnosed with chronic illness. The outcomes showed that the overall percentage of students with normal weight was 54%, 56%, and 53% during the 2019-2021 years, respectively. Overweight among students increased during the COVID-19 pandemic years, as almost 10% of the students were overweight in 2019 compared with 12% in 2020 and 2021 years. Besides, obese students also increased in the 2020-2021 period compared with the 2019 year (15-17% vs. 10%). In contrast, underweight trends among students declined, as 26% reported in 2019 compared to 17-18% in 2020 and 2021. Conclusion: There are significant variations in Arabic school-age students regarding their BMI values. Obesity was highly detected among children and adolescents during the COVID-19 pandemic years compared to 2019, while underweight cases declined.

Determining the genetic contribution of susceptibility to severe SARS-CoV-2 infection outcomes is important for public health measures and individualized treatment. Through intense research on this topic, several hundred genes have been implicated as possibly contributing to the severe infection phenotype(s); however, the findings are complex and appear to be population-dependent. We aimed to determine the contribution of human rare genetic variants associated with a severe outcome of SARS-CoV-2 infections and their burden in the Slovenian population. A panel of 517 genes associated with severe SARS-CoV-2 infection were obtained through an extensive review of the literature, and additionally included target genes identified by the COVID-19 Host Genetic Initiative, as well as the curated Research COVID-19 associated genes from PanelApp, England Genomics. Whole genome sequencing was performed using PCR-free WGS on DNA from 60 patients hospitalized due to severe COVID-19 disease, and the identified rare genomic variants were analyzed and classified according to the ACMG criteria. Background prevalence in the general Slovenian population was determined by comparison with sequencing data from 8025 individuals included in the Slovenian genomic database (SGDB). Results show that several rare pathogenic/likely pathogenic genomic variants in genes CFTR, MASP2, MEFV, TNFRSF13B, and RNASEL likely contribute to the severe infection outcomes in our patient cohort. These results represent an insight into the Slovenian genomic diversity associated with severe COVID-19 outcome.

Purpose: To explore how race and residential zip codes' socioeconomic index (SES) influenced COVID-19 testing rates in St. Louis during the early and peak phases of the pandemic. Method: An ecological study was conducted using COVID-19 testing data from March to November 2020 in St. Louis City. The study included 16,915 individual tests from 30 residential zip codes. Results: The overall testing rate in St. Louis was 303.97 per 10,000 population. Testing rates among Blacks, Whites, American Indian/Alaskan Natives, and Asians were 374.26, 247.77, 360.63, and 242.41 per 10,000, respectively. Higher testing rates were observed in low and middle SES zip codes compared to high SES zip codes. Adjusted for SES, testing rates were 1.68% higher among Blacks and 0.43% higher among American Indian/Alaskan Natives compared to Whites, and 0.033% lower among Asians. Geographical mapping showed higher testing rates in the inner core and lower rates in the periphery of St. Louis. Conclusion: Race and SES influence testing rates. Areas with low testing rates should be targeted for intervention in St. Louis.

The coronavirus disease caused by SARS-CoV-2 (known as COVID 19) is highly contagious and has spread rapidly over 200 countries over last three months. WHO suggested urgent escalation in testing, isolation and contact tracing, as the "backbone" of managing the pandemic. Globally, the detection of SARS-CoV-2 in patients are done by RT-PCR and blood antibody-based testing. In addition to the existing processes, flow-cytometry could be used as a high-throughput and efficient diagnostic method for detection of COVID 19. The suspected COVID 19 samples can be analyzed using ‘Indirect flow cytometry’, with the specific primary antibody and fluorescent tagged secondary antibodies. The fluorescence signal can distinguish the infected v/s non-infected samples. In the present article, we have summarized the applications of Flow virometry to study various viruses and have proposed possible application in the detection of COVID 19.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

Coronavirus disease 2019 (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached a global epidemic across the world after first reported in Wuhan, China’s Hubei province in December 2019. The pandemic is also associated with acute respiratory distress syndrome (ARDS) characterized by excess inflammation, progressive arterial hypoxemia and dyspnea. Mesenchymal stem/ stromal cells (MSCs) have been investigated as treatment for ARDS due to immunomodulatory property. Exosomes derived from MSCs play an important role in paracrine signaling of MSCs, thereby contributed to immunomodulation of the immune microenvironment. Exosomes are emerged as potential alternative to MSC cell therapy with superiority of safety. In this review, we will introduce MSC-derived exosomes and briefly discuss current progress on MSCs and exosomes in ARDS, which may have clinical implications in pathogenesis and treatment of COVID-19.

Background: A growing number of studies have reported Coronavirus disease (COVID-19)-related to both respiratory and central nervous system dysfunctions. This study evaluates the neuromodulatory effects of spinal cord transcutaneous stimulation (scTS) on the respiratory functional state in healthy controls and patients with post-COVID-19 respiratory deficits as a step toward the development of a rehabilitation strategy for these patients.; Methods: In this before-after, interventional, case-controlled clinical study, ten individuals with post-acute COVID-19 respiratory deficits and eight healthy controls received a single twenty-minute-long session of modulated monophasic scTS delivered over the T5 and T10 spinal cord segments. Forced Vital Capacity (FVC), Peak Forced Inspiratory Flow (PIF), Peak Expiratory Flow (PEF), Time-To-Peak of Inspiratory Flow (tPIF), and Time-To-Peak of Expiratory Flow (tPEF) were assessed before and after the intervention; Results: In COVID-19 group, the scTS intervention led to significantly increased PIF (p= .040) and PEF (p= .049) in association with significantly decreased tPIF (p= .035) and tPEF (p= .013). In the Control Group, the exposure to scTS also resulted in significantly increased PIF (p= .010) and significantly decreased tPIF (p= .031). Unlike the results in COVID-19 group, there was significantly decreased PEF (p= .028) in association with significantly increased tPEF (p= .036). There were no changes for FVC after scTS in both groups (p= .67 and p= .503); Conclusions: In post-COVID-19 patients scTS facilitates excitation of both inspiratory and expiratory spinal neural networks leading to an immediate improvement of respiratory functional performance. This neuromodulation approach could be utilized in rehabilitation programs for patients with COVID-19 respiratory deficits.

COVID-19 Pandemic management has become the top priority of Government Institutions globally, which is justifiable seeing the high mortality of the disease. In India, Lockdowns by National, State and Local level administrations have greatly reduced the spread of the SARS COV-2 Virus. Some areas with a greater proportion of COVID-19 patients have been declared hotspots with increased restrictions on public activities through law enforcement. But quite often delay in identification of these hotspots leads to community transmission of the Virus thus aggravating the problem. A method to identify the areas which are at risk of becoming the next hotspot for the disease is the need of the hour[1]. In this Research document we will find the probable risk factors and make an appropriate scale to measure the vulnerability of an area, identified by its Postal code. To help with this a Pan India survey by the title of “Survey on General Indian population on the level of preparedness for COVID-19 pandemic” was launched and received around 1250 submissions, with the acquired data we will evaluate the risk factors and make appropriate scale to identify ‘pre-hotspots’.

This study aimed to delineate the longitudinal antibody responses to the Pfizer- BioNTech COVID-19 vaccine (BNT162b2) within the Ugandan subset of the Sub-Saharan African (SSA) demographic, filling a significant gap in global datasets. We enrolled 48 participants, collecting 320 specimens over 12 months after vaccination. A validated enzyme-linked immunosorbent assay (ELISA) was used to quantify SARS-CoV-2-specific IgG, IgM, and IgA concentrations (ng/ml) and optical densities (ODs). Statistical analyses included box plots, diverging bar graphs, and the Wilcoxon test with Bonferroni correction. We showed a robust SIgG response within 14 days of the primary vaccine dose, consistent with global data. Remarkably, we observed no significant surge in S-IgG levels following the booster, contrasting trends other global populations. The S-IgM response was transient, and predominantly established thresholds, reflecting its typical early emergence and subsequent decline. S-IgA increased initially but declined six months post-vaccination, in line with the temporal dynamics of mucosal immunity. Eleven breakthrough infections occurred; however, all were asymptomatic, indicating a protective effect from the vaccination regardless of the participants' initial S-IgG serostatus. The Pfizer-BioNTech COVID-19 vaccine elicited strong S-IgG responses in the SSA demographic. However, antibody dynamics distinctly differed from global data highlight the significance of region-specific research and the necessity for customized vaccination strategies.

Effects of oxygen content on microstructure and creep property of FGH96 superalloy were investigated. When oxygen content increased from 135ppm to 341ppm, prior particle boundary (PPB) rose from degree 2 to degree 3, and the size of γ′ phase on PPB enlarged from 1.07μm to 1.27μm, and MC carbide size grew from 77.4nm to 104.0nm. Meanwhile, the steady creep rate accelerated form 4.34×10-3 h-1 to 1.87×10-2 h-1, and the creep rupture life shortened from 176h to 94h, and the creep rupture mode transferred from intergranular and transgranular mixed fracture to along PPB fracture. During creep, the micro-twins formation and gliding will be restrained by ∑3 boundaries. FGH96 superalloy with higher oxygen content contains less ∑3 boundaries and its micro-twins cross slipped instead of single direction slip in lower oxygen content superalloy. Consequently, specimen with higher oxygen content creeped faster and raptured earlier.

In the process of oil and gas development and production, when the flow rate in the wellbore is large, the materials underground will be eroded, causing the operation to be unable to proceed smoothly and reducing the efficiency of oil and gas production. Therefore, optimizing the anti-erosion coating under high-speed flow conditions in wellbore is a very interesting thing. It can greatly improve operational efficiency. In this paper, laser cladding was used to prepare the new coating used in the PDC drill bit. Then, the effects of tungsten carbide and multi-layer graphene on the microstructure and properties of the tungsten carbide coating were studied. The research results indicate that, for new coatings, 60% tungsten carbide and 0.3% graphene are the optimal ratios. After adding WC, the hardness has significantly improved. However, when the WC content further increases more than 30%, the increase in hardness is relatively small. In addition, when the content of graphene is more than 0.3%, the branched structure became thicker, and not only the segregation of Cr, Si and W became very obvious again, but also the segregation of Fe occurred at the Ni enrichment site. The research results contribute to improving oil and gas production and operational efficiency under high-speed fluid flow conditions in the wellbore.

Smoking a cigarette before bed or first thing in the morning is a common habit. In this review the relationship between smoking and sleep is investigated, based on the existing literature. Tobacco smoking disrupts sleep architecture by reducing slow wave and rapid eye movement (REM) sleep and undermining sleep quality. Furthermore, smoking affects sleep-related co-morbidities, such as obstructive sleep apnoea-hypopnea syndrome (OSAHS), insomnia, parasomnias, arousals, bruxism, restless legs but also non-sleep-related conditions such as cardiovascular, metabolic, respiratory, neurologic, psychiatric, inflammatory, gynecologic and pediatric. This review aims to consolidate all the existing knowledge about the relationship between smoking and sleep.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections in young children worldwide. RSV-associated deaths in children are underreported in Bangladesh. We analyzed hospital-based surveillance data on severe acute respiratory infections (SARI) in under-five children before (August 2009–February 2020) and during the COVID-19 pandemic (March 2020–March 2022). Using the World Health Organization definition, we identified SARI cases in 14 tertiary-level hospitals. Nasopharyngeal and oropharyngeal swabs were collected for real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) testing of six respiratory viruses, including RSV. SARI deaths during the pandemic (2.6%, 66) were higher than pre-pandemic (1.8%, 159; p<0.001). Nearly half of pandemic deaths (47%) had underlying respiratory viruses, similar to the pre-pandemic rate (45%). RSV detection in deaths was consistent pre-pandemic (13%, 20/159) and during the pandemic (12%, 8/66). Children aged <6 months constituted 57% (16) of RSV-related deaths. Evaluating interventions like maternal vaccination and infant monoclonal antibody prophylaxis is crucial to address RSV, a major contributor to under-five SARI deaths.

In geotechnical engineering applications, it is very important to obtain the undrained shear strength of remolded soils accurately and reliably. This study aims to obtain a trustworthy solution to determine the undrained shear strength of remolded clay mixtures using Atterberg limit test results in various states of consistency. An experimental study was carried out involving a wide range of clay mixtures of varying plasticity and geological origin. In the analyses, the variation of the remolded undrained shear strength depending on the cone penetration depth, water content, flow index, liquidity index and log liquidity index were investigated. In the study, the highest undrained shear strength of 100% Na-montmorillonite (NaM) was obtained at 171.89 kPa at 56.60% water content, while the lowest undrained shear strength was obtained for 100% Sepiolite (S), 9.28 kPa at 31.65% water content. The results of this study revealed that the shear strength is significantly affected by soil conditions, rather than dominant clay mineral. Besides, it was observed that the undrained shear strength at the plastic limit was approximately 30-35 times greater than that at liquid limit. The equations of liquid limit-flow index and plasticity index- flow index were proposed. It was concluded that the interdependence between undrained shear strength, liquidity index, log liquidity index, and flow index is not unique due to the different physical and chemical properties of clays.

We report the case of a 61-year-old woman who was referred to the Oral Surgery and Implantology Unit of the University Hospitals of Geneva to take care edentulous sites after dental avulsions of teeth 11 and 21 following traumatic shock due to endotracheal intubation under general anaesthesia. The dental history revealed that the patient had a history of generalized chronic periodontitis that had been treated several years earlier. Treatment consisted, for the first time to our knowledge, of immediate insertion of implants at sites 11 and 21 with simultaneous bone augmentation in a single surgical procedure and immediate restorations.

We assessed depression, anxiety, and stress in healthcare workers (HCWs) in 2023 and the evo-lution of depression in 2023 compared with 2022. In September-November 2023, 181 HCWs from the Infectious Diseases Hospital, Cluj-Napoca, Romania, completed the Depression, Anxiety, and Stress 21 Scale (DASS-21 R), the Patient Health Questionnaire-9 (PHQ-9), and the Hamilton Anxiety Rating Scale (HAM-A). The prevalence of moderate-to-severe levels was 13.81% for DASS-Depression, 18.79% for DASS-Anxiety, 16.02% for DASS-Stress, 19.89% for PHQ-9, and 12.16% for HAM-A. Moderate-to-severe PHQ-9 clinical depression was found in 19.89% of respondents, and moderate-to-severe HAM-A clinical anxiety in 12.16%. Moderate-to-severe PHQ-9 depres-sion was significantly lower in the 2023 study group (19.89%, N=181) compared with 2022 (30.60%, N=114) (p=0.036), also within the 2022-2023 follow-up study group (N=88) (p=0.026). We did not find significant statistical differences between those infected vs. non-infected, vaccinated vs. non-vaccinated, working with vs. non-working with SARS-CoV-2 infected patients. Males were significantly more stressed (p=0.018) and anxious (p=0.034), and physicians in training had the highest prevalence of moderate-to-severe depression (31.60%), followed by physicians (25.64%). In 2023, depression, anxiety, and stress symptoms decreased but remained within a concerning range. By addressing these psychological issues, we can prevent professional crises in the healthcare system.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Objectives: There are limited data regarding the efficacy of methylprednisolone in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation. We aimed to determine whether methylprednisolone increases the number of ventilator-free days (VFDs) among these patients. Design: Retrospective single-center study Setting: Intensive care unit Patients: All patients with ARDS due to confirmed SARS-CoV-2 infection and requiring invasive mechanical ventilation between 1 March and 29 May 2020 were included Interventions: None Measurements and Main Results: The primary outcome was ventilator-free days (VFDs) during the first 28 days, defined as being alive and free from mechanical ventilation. The primary outcome was analyzed with competing-risks regression based on Fine and Gray’s proportional subhazards model. Death before day 28 was considered to be the competing event. A total of 77 patients met the inclusion criteria. Thirty-two patients (41.6%) received methylprednisolone. The median dose was 1 mg.kg-1 (IQR: 1-1.3 mg.kg-1) and median duration of 5 days (IQR:5-7 days). Patients who received methylprednisolone had a mean 18.8 VFDs (95% CI, 16.6-20.9) during the first 28 days vs. 14.2 VFDs (95% CI, 12.6-16.7) in patients who did not receive methylprednisolone (difference, 4.61; 95% CI, 1.10-8.12; P = 0.001). In the multivariable competing-risks regression analysis and after adjusting for potential confounders (ventilator settings, prone position, organ failure support, severity of the disease, tocilizumab, and inflammatory markers), methylprednisolone was independently associated with a higher number of VFDs (subhazards ratio: 0.10, 95%CI: 0.02-0.45; p=0.003). Hospital mortality did not differ between the two groups (31.2% vs. 28.9%, p=0.82). Hospital length of stay was significantly shorter in the methylprednisolone group (24 days [IQR:15-41 days] vs. 37 days [IQR:23-52 days], p=0.046). The incidence of positive blood cultures was higher in patients who received methylprednisolone (37.5% vs. 17.8%, p=0.052). However, 91% of patients who received methylprednisolone also received tocilizumab. The number of days with hyperglycemia was similar in the two groups. Conclusions: Methylprednisolone was independently associated with increased VFDs and shortened hospital length of stay. The combination of methylprednisolone and tocilizumab was associated with a higher rate of positive blood cultures. Further trials are needed to evaluate the benefits and safety of methylprednisolone in moderate or severe COVID-19 ARDS.

Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in young children globally. Following the COVID-19 pandemic, RSV infections have become more prevalent. Consequently, a new vaccine targeting RSV infections in pregnant women has been introduced worldwide. To estimate the effectiveness of this new vaccine for pregnant women, we investigated neutralizing antibodies against RSV in samples taken from 51 mothers and their babies. The prevalence rate of neonatal antibodies, defined as a titer of ≥16, was 39.2%. We found no significant differences in neonatal neutralizing antibodies based on factors, such as sex, gestational age at birth, birth weight, presence of siblings, neonatal problem, and usage of palivizumab. Neonatal neutralizing antibodies were equal to or higher than those of their mother. A new RSV vaccine targeting all pregnant women is promising, as approximately 60% of neonates had low antibody titers against RSV. However, predicting low antibody titer against RSV remains challenging. Moreover, our findings indicate efficient transmission of RSV antibodies from babies to their mothers.

Objective: Several authors have analyzed the impact of the pandemic on the incidence rates of different conditions. Our aim was to analyze the impact of the COVID-19 pandemic on primary care new diagnoses of respiratory diseases. Methods: This was an observational retrospective study performed to describe the impact of COVID-19 pandemic on primary care new diagnosis of respiratory diseases other than lung cancer. Incidence rate ratio between pre-pandemic and pandemic period was calculated. Results: We found an decrease in the incidence of respiratory conditions (IRR 0.65) during the pandemic period. When we compared the different groups of diseases according to ICD-10, we found a significant decrease in the number of new cases during the pandemic period, except in the case of pulmonary tuberculosis, abscesses or necrosis of the lungs and other respiratory complications. Instead, we found increases in new diagnoses of flu and pneumonia (IRR 2.17) and respiratory interstitial diseases (IRR 1.41). Conclusion: There has been a decrease in new diagnosis of most respiratory diseases during the COVID-19 pandemic. The real clinical impact of this situation is still unknown. Large-scale real-life studies will make it possible to evaluate the long-term true impact of COVID-19 pandemic on the respiratory diseases management.

The COVID-19 pandemic has underscored the intricate interplay between viral infections and opportunistic bacterial pathogens such as Klebsiella pneumoniae. K. pneumoniae harbors various antibiotic resistance determinants like extended-spectrum and plasmid-mediated AmpC β-lactamases and carbapenemases. In the two years following the pandemic, carbapenemase producing K. pneumoniae isolates obtained routinely in outpatient and inpatient setting demonstrated similar resistance patterns which prompted research. The aim was to compare and subsequently analyze carbapenem-resistant hospital and outpatient’s K. pneumoniae isolates’ resistance mechanisms, traits and molecular epidemiology, following the COVID-19 pandemic. Disk diffusion and broth dilution method were the methods of choice to determine antibiotic susceptibility. β-lactamases were screened by phenotypic methods and confirmed with PCR. In total 113 isolates were analysed. Resistance to amoxicillin-clavulanate and ertapenem was confirmed in all strains. High resistance rates (over 90%) were observed for extended-spectrum cephalosporins, and ciprofloxacin. OKNV testing and PCR detected OXA-48 in 106, NDM in 7 and KPC in only one isolate. ESBLs accompanied carbapenemases in 103 isolates. Carbapenem resistance in K. pneumoniae is becoming a global problem, hence careful monitoring of its resistance traits is of utmost importance in order to combat the arising threat. OXA-48 seems to continue predominating in the turbulent period after pandemic.

Many individuals are wearing face masks improperly at ‘half mask’ and potentially breathing out microbes that can contaminate the air as well as anything below the nose. This note provides the first report that bacteria and fungi breathed out during nasal air exhalation are able to be cultured after landing on blood agar plates. The CFU’s are higher after both 10 breaths and extremely significant for 20 breaths compared to the control plates exposed to the air. Implications of this finding are that going ‘nose commando’ may be able to continue the spread of respiratory diseases such as COVID-19.

The oscillating heat pipe (OHP) is a new member in the family of heat pipes, and it has great potential applications in energy conservation. However, the fluid flow and heat transfer in the OHP as well as the fundamental effects of inner diameter on them have not been fully understood, which are essential to the design and optimization of the OHP in real applications. Therefore, by combining the high-speed visualization method and infrared thermal imaging technique, the fluid flow and thermal performance in the OHPs with inner diameters of 1, 2 and 3 mm are presented and analyzed. The results indicate that three fluid flow motions, including small oscillation, bulk oscillation and circulation, coexist or, respectively, exist alone with the increasing heating load under different inner diameters, with three flow patterns occurring in the OHPs, viz. bubbly flow, slug flow and annular flow. These fluid flow motions are closely correlated with the heat and mass transfer performance in the OHPs, which can be reflected by the characteristics of infrared thermal images of condensers. The decrease in the inner diameter increases the frictional flow resistance and capillary instability while restricting the nucleate boiling in OHPs, which leads to a smaller proportion of bubbly flow, a larger proportion of short slug flow, a poorer thermal performance, and easier dry-out of working fluid. In addition, when compared with the 2 mm OHP, the increasing role of gravity induces the thermosyphon effect and weakens the 'bubble pumping' action, which results in a little smaller and bigger thermal resistances of 3 mm OHP under small and bulk oscillation of working fluid, respectively.

Background/Objectives: The aim of this study was to investigate feasibility and safety of neuromuscular electrical stimulation (NMES) in patients on extracorporeal membrane oxygenation (ECMO) and assess thoroughly any potential adverse events. Methods: We conducted a safety and feasibility study including 16 ICU patients on ECMO support who were admitted to the cardiac surgery ICU from January 2022 to December 2023. Patients underwent a 45-minute NMES session, still on ECMO support, that included a warm up phase of 5 minutes, a main phase of 35 minutes and a recovery phase of 5 minutes. NMES was implemented on vastus lateralis, vastus medialis, gastrocnemius and peroneus longus muscle of both lower extremities. Two stimulators delivered biphasic, symmetric impulses of 75 Hz, with 400 μsec pulse duration, 5 sec on (1,6 sec ramp up and 0,8 sec ramp down) and 21 sec off. The intensity levels aimed to cause visible contractions and be well tolerated. Primary outcomes of the study were feasibility and safety, evaluated by whether the NMES sessions were successfully achieved, and by any adverse events and complications. Secondary outcomes included indices of rhabdomyolysis from biochemical blood test, 24 hours after the application of NMES. Results: All patients successfully completed their 45-minute NMES session, without presenting hemodynamic deterioration, adverse events or signs of rhabdomyolysis. The majority of patients achieved type 4 and 5 quality of muscle contraction. Conclusions: NMES is a safe and feasible exercise methodology in patients supported with ECMO.

Adolescence is a central phase for the development of a person’s identity involving complex multidimensional changes and increasing vulnerability to distress. The aim of this study was to investigate the psychological well-being of adolescent students in Brescia (Northern Italy), two years after the beginning of the Covid-19 pandemic. An online survey investigated the extent and the reasons reported by high school students for their emotional distress (ED), also considering other factors such as physical activity, diet, sleep and smartphone overuse. The main reasons for ED were classified through a qualitative analysis of the freetext answers. 1686 students agreed to participate, 50% showed a presence of ED. According to a multiple logistic analysis, the main factors associated to ED were female gender (AdjOR 2.3, p<0.0001), age (AdjOR 1.6, p<0.0001), sleep duration <8 hours (AdjOR 1.5, p=0.0003), anxiety perception (AdjOR 3.4, p<0.0001), and certain eating behaviors, e.g. comfort food consumption (AdjOR 2.0, p<0.0001). According to free-text answers, the main reasons for ED were: “school pressure”, “ relationships with family and peers”, “negative emotional states” and “the pandemic”. The results show a high level of ED among adolescents and the reported reasons may help to better address their psychological needs after the pandemic.

This paper presents a new semi-explicit algorithm for parameters estimation in a time-fractional generalization of dual-phase-lag heat conduction model with the Caputo fractional derivatives. It is shown that this model can be derived from a general linear constitutive relation for the heat transfer by conduction when the heat conduction relaxation kernel contains the Mittag-Leffler function. The model can be used to describe heat conduction phenomena in a material with power-law memory. The proposed algorithm of parameters estimation is based on the time integral characteristics method. The explicit representations of the thermal diffusivity and the fractional analogues of the thermal relaxation time and the thermal retardation are obtained via a Laplace transform of the temperature field and utilized in the algorithm. An implicit relation is derived for the order of fractional differentiation. In the algorithm, this relation is resolved numerically. An example illustrates the proposed technique.

Two series of novel [1,2,4]triazolo[4,3-c]- and [1,2,4]triazolo[1,5-c]quinazoline fluorophores with 4’-amino[1,1′]-biphenyl residue at position 5 have been prepared via Pd-catalyzed cross-coupling Suzuki-Miyaura reactions. The treatment of 2-(4-bromophenyl)-4-hydrazinoquinazoline with orthoesters in solvent-free conditions or in absolute ethanol leads to the formation of [4,3-c]-annulated triazoloquinazolines, whereas [1,5-c] isomers are formed in acidic media as a result of Dimroth rearrangement. 1D-NMR and 2D-NMR spectroscopy as well as single‐crystal X‐ray diffraction analysis unambiguously confirmed the annelation type and determined the molecular structure of p-bromophenyl intermediates and target products. Photophysical properties of the target compounds were investigated in two solvents and solid state and compared with those of related 3-aryl-substituted [1,2,4]triazolo[4,3-c]quinazolines. The excluding of aryl fragment from triazole ring has been revealed to improve fluorescence quantum yield in solution. Most of the synthesized structures show moderate to high quantum yields in solution. Additionally, the effect of solvent polarity on the absorption and emission spectra of fluorophores has been studied and considerable fluorosolvatochromism was stated. Moreover, electrochemical investigation and DFT calculations have been performed, their results are consistent with the experimental observation.

Evaluation of the usefulness of [18F]FDG-PET/CT in the short-term follow-up of patients admitted for COVID-19 pneumonia and to explore the association of findings with clinical prognostic markers. Prospective study included 20 patients admitted to hospital with COVID-19 pneumonia between November 2020 and March 2021. Clinical and laboratory test findings were gathered at admission, 48-72h post-admission, and 2-3 months post-discharge. [18F]FDG-PET/CT and respiratory function tests were performed at 2-3 months post-discharge. Lung volumes (TLC), spirometry (FVC, FEV1), lung diffusion capacity for carbon monoxide (DLCO), and respiratory muscle strength were measured. PET/CT images were qualitatively and semi-quantitatively interpreted. Volumetric [18F]FDG-PET/CT results were correlated with laboratory test and respiratory parameters. Eleven [18F]FDG-PET/CT (55%) were positive. The main finding was hypermetabolic lymphade-nopathy in the mediastinum (90.9%). SUVpeak of the target mediastinum lesion was correlated with neutrophil and lymphocyte counts. Eleven (55%) patients had impaired respiratory function, most frequently a reduced DLCO (35%). SUVpeak was positively correlated with %predict-ed-DLCO values. Pulmonary TLG was negatively correlated with %predicted-DLCO and TLC values. In the short-term follow-up of patients hospitalized for COVID-19 pneumonia, [18F]FDG-PET/CT findings revealed significant detectable inflammation in lungs and mediastinal lymph nodes that correlated with pulmonary function impairment in more than half of the patients.

Celecoxib as adjuvant therapy has been shown in a small randomized trial for Covid-19 to prevent clinical deterioration and rapidly improve thoracic computerized axial tomography (CT-chest)¹. Multiple descriptive trials of high dose famotidine (both inpatient and outpatient) have demonstrated clinical response^2,3,4. We describe the rapid clinical responses after increasing the celecoxib dosage to 400mg bid with high dose famotidine 80mg qid in both a critical inpatient who on baseline required 40 liters per minute high flow nasal insufflation and an outpatient who declined admission but had critical Covid-19 biomarkers.

This study aimed to determine shifts in microbial populations regarding richness and diversity from the daily use of a popular over-the-counter nasal spray. In addition, the finding of nasal commensal bacterial species that overlap with the oral microbiome may prove to be potential probiotics for the “gateway microbiomes.” Nasal swab samples were obtained before and after using the most popular over-the-counter (OTC) nasal spray in 10 participants aged 18–48. All participants were healthy volunteers with no significant medical histories. The participants were randomly assigned a number by randomizing software and consisted of five men and five women. The sampling consisted of placing a nasal swab atraumatically into the nasal cavity. The samples were preserved and sent to Northwestern University Sequencing Center for whole-genome deep sequencing. After 21 days of OTC nasal spray use twice daily, the participants returned for further nasal microbiome sampling. The microbial analysis included all bacteria, archaea, viruses, molds, and yeasts via deep sequencing for species analysis. The Northwestern University Sequencing Center utilized artificial intelligence analysis to determine shifts in species and strains following nasal spray use that resulted in changes in diversity and richness.

The different waves of the COVID-19 pandemic caused dramatic issues regarding the organiza-tion of care. In this context innovative solutions have to be developed in a timely manner to adapted the organization of the care. The establishment of middle care (MC) units is a bright example of such an adaptation. A multidisciplinary MC team, including expert and non-expert respiratory nurses, physicians, physiotherapists, psychologists, nutritionists and social workers, was built and trained to work in the COVID-19 MC unit. Important educational resources were set up to ensure rapid and effective training of the MC team, limiting the admission or delaying transfers to ICU and ensuring optimal management of palliative care. We conducted a retrospec-tive analysis of patient data in the MC unit during the second COVID-19 wave. Fifty-two COVID-19 ‘step-up’ patients admitted to the MC unit were included in the study. Thirty-four (65%) patients worsened, of which 12 (23%) were not eligible for ICU access. In total, 42% of the ICU-eligible patients were managed in the MC unit to avoid the ICU. Among the 22 patients transferred to the ICU, 15 were intubated. The establishment of an MC unit during a pandemic, mixing expert and non-expert respiratory team members, is feasible and needed. MC units possi-bly relieve the pressure exerted on ICUs. A highly trained multidisciplinary team is key to ensur-ing the success of an MC unit during a pandemic.

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.

The coronavirus disease–2019 pandemic created major obstacles for effective smoking cessation programs by significantly limiting access to healthcare. This retrospective study aimed to assess the effectiveness of a self-developed smoking cessation program during the pandemic. The program was based on remote lectures, educational interventions, and hybrid services provided by an outpatient clinic. We enrolled 513 participants between January 2019 and February 2022. Data on demographic characteristics, medical history, and smoking status at baseline and after at least 1-year follow-up were collected from medical records and a standardized self-developed questionnaire. Participants were classified into two groups according to their current smoking status. The smoking cessation rate at 1 year was 37%. Major predictors of smoking cessation were the place of residence, ability to refrain from smoking during severe illness, and the number of cigarettes smoked per day. The proportion of participants with high levels of nicotine dependence at baseline was 40.8% vs 29.1% at 1 year (p=0.003). In the group that did not quit smoking, there were more participants who smoked within 5 minutes after waking up, as compared with participants who quitted smoking (40.4% vs 25.4%; p=0.0004). Effective smoking cessation interventions can be performed using remote counseling and education.

SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 pandemic. It was listed as a potential global health threat by WHO due to high mortality, high basic reproduction number and lack of clinically approved drugs and vaccines for COVID-19. The genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three dimensional structure of the Main protease (Mpro) are available. The reported structure of the target Mpro was utilized in this study to identify potential drugs for COVID-19 using molecular docking based virtual screening of all approved drugs. The results of this study confirm preliminary reports that some of the drugs approved for treatment of other viral infections have the potential for treatment of COVID-19. Selected antiviral drugs, approved for human therapeutic applications, were ranked for potential effectiveness against COVID-19, based on predicted binding energy to the target Mpro of SARS-CoV-2, and novel candidates for drug repurposing were identified in this study. In addition, potential mechanisms for beneficial off target effects of some drugs in clinical trials were identified by using molecular docking.

Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF.

The domestic ducks (Anas platyrhynchos domesticus) are resistant to most of the highly pathogenic avian influenza virus (HPAIV) infections. In this study, we characterized the lung proteome and phosphoproteome of ducks infected with HPAI H5N1 virus (A/duck/India/02CA10/2011/Agartala) at 12 hr, 48 hr and 5 days post infection condition. Total 2082 proteins were differentially expressed and 320 phosphorylation sites mapping to 199 phosphopeptides corresponding to 129 proteins were identified. Functional annotation of proteome data analysis reveals activation of RIG-I-like receptor and Jak-STAT signaling pathways, that lead to induction of interferon stimulated genes (ISGs) expression. The pathway analysis of phosphoproteome datasets also confirms the activation of RIG I, Jak-STAT signaling, NF-kappa B signaling and MAPK signaling pathways in the lung tissues. The induction of ISGs proteins (STAT1, STAT3, STAT5B, STAT6, IFIT5 and PKR) establishes protective antiviral immune response in duck lung tissue. Further, the protein-protein interaction network analysis identified proteins like AKT1, STAT3, JAK2, RAC1, STAT1, PTPN11, RPS27A, NFKB1 and MAPK1 as main hub proteins that might play important roles in disease progression in ducks. Together, functional annotation of proteome and phosphoproteome datasets reveals the molecular basis of the disease progression and disease resistance mechanism in ducks infected with HPAI H5N1 virus.

The B169L protein (pB169L) of African swine fever virus (ASFV) is a structural protein with an unidentified function during the virus replication. The sequences of the B169L gene and the downstream B438L gene are separated by short intergenic regions. However, the regulatory mode of the gene transcription remains unknown. Here, we identified two distinct promoter regions and two transcription start sites (TSS) located upstream of the open reading frame (ORF) of B438L. Using the promoter reporter system, we demonstrated that the cis activity of the ORF proximal promoter exhibited significantly higher levels compared with that of the distal promoter located in the B169L gene. Furthermore, transfection with the plasmids with two different promoters for B438L could initiate the transcription and expression of the B438L gene in HEK293T cells, and the cis activity of the ORF proximal promoter also displayed the higher activities compared with the distal promoter. Interestingly, the B438L distal promoter also initiated the transcription of the alternatively spliced B169L mRNA (B169L mRNA2) encoding a truncated pB169L (tpB169L) (amino acids 92–169), and the gene transcription efficiency was increased upon mutation of the initiation codon located upstream of the alternatively spliced B169L gene. Taken together, we demonstrated that the distal promoter of B438L gene initiates the transcription of both the B438L mRNA and B169L mRNA2. Comprehensive analysis of the transcriptional regulatory mode of the B438L gene is beneficial for the understanding of the association of B438L protein and pB169L and the construction of the gene-deleted ASFV.

Regardless of the SARS-CoV-2 pandemic containment, it remains paramount to comprehensively understand its underlying mechanisms to mitigate potential future health and economic impacts, comparable to those experienced throughout the course of the pandemic. The angiotensin-converting enzyme 2 (ACE2) provide anchorage for SARS-CoV-2 binding, thus implicating that ACE and ACE2 might contribute to the variability in infection severity. This study aimed to elucidate predisposing factors influencing the disease course among people infected by SARS-CoV-2, focusing on angiotensin-converting enzyme (ACE) and ACE2 polymorphisms. Notably, despite similar demographics and comorbidities, COVID-19 patients exhibit substantial differences in prognosis. Genetic polymorphisms in ACE and ACE2 have been implicated in disease progression, prompting our investigation into their role in COVID-19 evolution. Using next-generation sequencing (NGS), we analyzed ACE and ACE2 genes in a sample group comprising six subjects infected by SARS-CoV-2. Our findings revealed a correlation between specific polymorphisms and COVID-19 outcomes. Specifically, ACE and ACE2 intronic deletions were observed in all deceased patients, suggesting a potential association with mortality. These results highlight the significance of genetic factors in shaping the clinical course of COVID-19, emphasizing the importance of further research into the impact of genetic variations on COVID-19 severity.

Microscopic vision plays an important role in automated micro-assembly. However, some uncertain factors in the assembly process, such as occlusion and stains can lead to the mistakes of feature extraction. Herein, to solve the problem, the deep learning techniques are introduced into the feature recognition tasks, focusing on the attention mechanism and visualizing CNNs for DL-based microscopic vision. The main contributions are summarized as follows: The CBAM attention mechanism is combined with the YOLOv5 algorithm to improve the accuracy and robustness of feature extraction. The micropart feature occlusion experiment results show that at 70% occlusion degree, YOLOV5-CBAM can reach 97.9% [email protected], which is 4.6% higher than the original one. Visualization analysis of DL-based model is conducted using Grad-CAM to make the decision result more transparent and avoid potential visual detection risks during assembly. The heatmap matching degree between GT area and high-light area is increased by 27.81% on average, which further verify the effectiveness of attention mechanism in micropart feature localization. Additionally, micropart surface stain and droplet quality classification models based on ResNet50 are trained to replace the manual sorting. The visual results are consistent with human eye discernment and judgement, confirming the reliability of parts and droplets sorting.

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.

Access to nasopharyngeal swabs for sampling remain a bottleneck in some regions for COVID-19 testing. This study develops a distributed manufacturing solution using only an open source manufacturing tool chain consisting of two types of open source 3-D printing and batch UV curing, and provides a parametric fully free design of a nasopharyngeal swab. The swab was designed using parametric OpenSCAD in two components (a head with engineered break point and various handles), which has several advantages: i) minimizing print time on relatively slow SLA printers, ii) enabling the use of smaller print volume open source SLA printers, iii) reducing the amount of relatively expensive UV resin, and iv) enabling production of handle on more accessible material extrusion 3-D printers. A modular open source UV LED box was designed, fabricated for $45 and tested for batch curing. Swabs can be fabricated for $0.06-$0.12/swab. The results of the mechanical validation tests showed that the swabs could withstand greater forces than would be expected in normal clinical use. The swabs were also able to absorb a significant amounts of synthetic mucus materials and passed abrasion and handling tests. The results show the open source swab are promising candidates for clinical trials.

This study investigates the effects of home-based Kakao health care breathing exercises and stretching on respiratory function and fatigue in COVID-19 cured patients. A total of 35 participants performed four movements of home-based breathing exercise and five respiratory muscle stretching exercises four times a week for four weeks. Respiratory function was measured using FVC, FEV1, FEV1/FVC, and PEF. Fatigue was assessed using the Fatigue Severity Scale (FSS). Data analysis was performed using Independent Samples and Paired Samples T-tests in SPSS 24, with a significance level set at p &lt; 0.05. After four weeks of Home based Kakao health care Breathing Exercise, there were significant increases in respiratory FVC, FEV1, FEV1/FVC, and PEF function values observed in the training group (T.G.) after the exercise intervention (p &lt; 0.05). Such an increase was observed when comparing these values with the pre-exercise measurements. In contrast, there was no statistically significant difference in respiratory function outcomes before and after exercise in the control group (C.G.) (p &gt; 0.05). The FSS scores were statistically significant within the training group (T.G.). (p &gt;0.05). The 4-week Kakao health care Breathing Exercise was found to be capable of improving some respiratory functions in COVID-19-recovered patients, but it showed no significant improvement in fatigue levels.

The use of alternative fuels and electric vehicles is an opportunity to reducing exhaust emissions. We observe that the regulations on exhaust emissions from mobile sources are becoming gradually stricter on the all the world. As is widely known, using alternative fuels instead of conventional fuels helps lower vehicle emissions. The most popular alternative fuels are hydrogen, propane, biobutanol, methanol, dimethyl ether, etc. It is very important that more than a dozen alternative fuels are under development. The article contains a comparison of the operating costs of electric cars and cars with an internal combustion engine. This work shows also the characteristic of new alternative fuels and their impacts on exhaust emissions.

The current pneumonia epidemic could evolve into a pandemic on a global scale if not effectively contained. The COVID-19 virus possesses a 61-amino acid open reading frame resembling SARS-CoV virulence factor - ORF6 peptide. The isoleucine content is 15.9% in ORF6 of SARS-CoV versus 16.4% of that in SARS-CoV-2. Given the proton affinity in the carbonyl oxygen in isoleucine, augmented proton traffic can enhance proton-ion antiport and prompt cell swelling. Calorie restriction has been confirmed in animal studies to extend lifespan, and its underlying mechanism is not fully known. As the content of essential amino acids in the open reading frame of SARS-CoV-2 reaches 57.4%, a starch/vitamin diet served for short period of time does not give rise to essential amino acids and halts virion production, which could be adopted as prophylactic approach of many viral infections. Plant-based diet or fasting/boiled rice water can also minimize the intake of essential amino acids or all amino acids respectively. Furthermore, several proteins of SARS-CoV-2 possess high valine plus glycine content which is implicated in heart disease, justifying the aforementioned approaches.

We describe a 90-year-old male presenting with disequilibrium, loss of balance and difficulty walking for three days prior to initial presentation. Interestingly, he denied cough, fever or dyspnea prior to arrival. Over the course of 48 hours, the patient developed acute respiratory distress syndrome (ARDS) requiring intubation, diagnosed with COVID-19 infection and was treated in the intensive care unit where he died. Since the initial cases in Wuhan China in Dec 2019, the medical and epidemiological communities have learned much about the presenting features, symptomatology, epidemiology, transmission and common physical, laboratory and radiological findings of this disease. Although common symptoms are already established, it is very important to learn and record atypical symptoms or presentations of this highly contagious disease. By doing so, we will be able to recognize earlier atypical symptoms and prevent the environmental exposure to Health care workers and future patients as well. We report that Central disequilibrium may be such as initial presenting sign and symptom of impending respiratory failure from SARS-CoV-2 virus. These atypical findings such as presyncope may precede common respiratory complications of SARS-CoV-2.

The Eastern Kunlun Fault Zone (EKFZ) is located in a seismic blank area. This study investigates the hydrogeochemical characteristics of varied-temperature springs in the EKFZ to understand the relationship between fractures, fluids and earthquakes. It aids in establishing their induction mechanisms and assists in monitoring the earthquake precursors of the EKFZ. In this study, the main elements, trace elements, hydrogen and oxygen isotopes and strontium isotopes of 23 varied-temperature springs in the EKFZ were analyzed. The results reveal the source of groundwater recharge, hydrochemical types, mineral saturation, and for a select few springs indicative of geothermal activity, collected geothermal reservoir temperatures. The study also explores the relationship between earthquakes and springs, identifying sensitive chemical indicators. Based on continuous monitoring at Maqu Station, we found that before the occurrence of the Maerkang Ms 6.0 earthquake, the concentration of Cl− rose by 2.9 times, and 46 days before the Gande earthquake (Ms = 4.7), the concentrations of Na+ and SO42− significantly increased. Finally, a conceptual model of the hydrogeochemistry of springs is presented to describe the groundwater circulation in the study area. This research is of great significance for the analysis of fluid geochemistry in this area and for assessing the seismic hazards of the EKFZ.

Idiopathic pulmonary fibrosis (IPF) is a difficult to treat condition to treat with a high mortality rate. While preclinical models such as Bleomycin (Bleo)-induced fibrosis recapitulate some aspects of IPF, new models that more closely mimic the disease are warranted. We have developed and characterized a novel model in BALB/c mice using a transient overexpression of IL-6 combined with Bleo. This model’s transcriptomic signature was compared to published human IPF datasets. BALB/c females were treated with AdIL-6 in combination with Bleo (AdIL-6+Bleo) or control comparators, and underwent assessments of histopathology (ECM, α-SMA accumulation), collagen content and lung physiology (Elastance, EST). Flow cytometry was used to characterize T cell and Macrophage subsets, and T cell depletion studies (anti-CD4/CD8) were completed to assess T cells role in fibrosis. Bulk RNA sequencing generated gene signatures were compared to that of other rodent fibrosis models and published human datasets of IPF datasets. The AdIL-6+Bleo treatment resulted in robust fibrosis measures (day21), sustained fibrosis until at least day 50, a unique cytokine profile at day 7, and increased activated CD4+Tcells, CD8+Tcells, and CD16+MHChi/Clec7a/iNOS-/Arg1-/CD206- macrophages. T cell depletion markedly decreased fi-brotic responses and this population of macrophages. The Day 21 AdIL-6+Bleo transcriptome shared more genes with each of two human IPF datasets than Bleo alone in C57Bl/6 mice or other rodent models. We conclude that AdIL-6+Bleo in BALB/c mice offers a superior preclinical model for studying IPF mechanisms and potential therapeutic intervention.

Following the detection of highly pathogenic avian influenza (HPAI) virus in countries bordering Kenya to the west, we conducted surveillance among domestic and wild birds along the shores of Lake Victoria. In addition, between 2018 and 2020, we conducted surveillance among poultry and poultry workers in live bird markets and among wild migratory birds in various lakes that are resting sites during migration to assess introduction and circulation of avian influenza viruses in these populations. We tested 7,464 specimens (oropharyngeal and cloacal swabs) from poultry and 6,531 fresh fecal specimens from wild birds for influenza A viruses by real-time RT-PCR. Influenza was detected in 3.9% (n=292) of specimens collected from poultry and 0.2% (n=10) of fecal specimens from wild birds. On hemagglutinin subtyping, most of the influenza A positives from poultry (274/292, 93.8%) were H9. Of 34 H9 specimens randomly selected for further subtyping, all were H9N2. On phylogenetic analysis, these viruses were genetically similar to other H9 viruses detected in East Africa. Only two of the ten influenza A positive specimens from the wild bird fecal specimens were successfully subtyped; sequencing analysis of one specimen collected in 2018 was identified as low pathogenicity avian influenza H5N2 virus of the Eurasian lineage and the second specimen, collected in 2020, was subtyped as H11. A total of 18 OP/NS swabs from poultry workers with ARI (12%) were collected; none were positive for influenza A virus. We observed significant circulation of H9N2 influenza viruses in poultry in live bird markets in Kenya. During the same period, low pathogenic H5N2 virus was detected in a fecal specimen collected in a site hosting a variety of migratory and resident birds. Although HPAI H5N8 was not detected in this survey, these results highlight the potential for introduction and establishment of highly pathogenic avian influenza viruses in poultry populations and the associated risk of spillover to human populations.

Predictive simulation of concurrent debris flow using only pre-disaster information has proven to be difficult as a result of problems in predicting the location of debris-flow initiation (i.e., slope failure). However, because catchment topography has concave characteristics, with all channels in a catchment joining each other as they flow downstream, it is possible to predict damage to downstream area using relatively inaccurate initiation points. Based on this, this paper presents methodologies employing debris-flow initiation points generated randomly using statistical slope failure prediction. A many-case simulation across numerous initiation points was performed to quantify the effect of slope-failure location in terms of deviations in the predicted water level and terrain deformation. It was found that the relative standard deviation diminished as the points approached the downstream area, indicating a location-based predictability effect.

Introduction: The objective of the study is to assess the failure of therapies with HFNO (High-Flow Nasal Oxygen), CPAP, Bilevel or combined therapy in patients with hypoxemic acute respiratory failure due to SARS-CoV-2 during their hospitalization. Methods: Retrospective and observational study of SARS-CoV-2 positive patients who required non-invasive respiratory support (NIRS), at the Reina Sofía General University Hospital of Murcia between March 2020 and May 2021. Results: Of 7355 patients, 197 (11,8%) were included. 95 of them failed this therapy (48,3%). We objectivated that during hospitalization in the ward the combined therapy with HFNO and CPAP had a lower failure rate overall and the highest treatment purely with Bilevel (p = 0,005). In the comparison of failure in therapy without two levels of airway pressure, HFNO, CPAP and combined therapy of HFNO with CPAP, (35,6% of patients) presented a 24,2% failure compared to those who did have two levels of pressure with Bilevel and combined therapy of HFNO with Bilevel (64,4% of patients) with 75,8% associated failure (OR: 0, 374; CI 95%: 0,203-0,688. p=0,001).Conclusions: The use of NIRS in conventional hospitalization is safe and effective in patients with respiratory failure secondary to SARS-CoV-2 infection. The therapeutic strategy with Bilevel increases the probability of failure, with the combined therapy strategy with CPAP and HFNO being the most promising option.

Less aligned emphasis has been given to the COVID-19 infodemic coordinating with the COVID-19 outbreak. Global profusion of tangled monikers and hashtags has found their ways in daily communication and contributed to backlash against Chinese. Official naming efforts against infodemic should be meet with a fair share of identification. Based on brief critical reviews on previous multifarious naming practices, we punctuate heuristic introspection in scientific conventions and sociocultural paradigms. Infodemiological analysis promises to articulate that people around the globe are divided in their favor stigmatized monikers in the public and scientific communities because of perceptual bias. There is no positive correlation between the degree of infection in their territories and collective perceptual bias to COVID-19. The official portfolio “COVID-19” and “SARS-CoV-2” has not become de facto standard usages, but full-fledged official names are excepted to duly contribute to the resilience of negative perceptual bias and collective behavioral propensities.

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalized. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected with PASC and its complications. The severity and the later development of PASC symptoms is positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. Cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as a condition that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with respiratory system in long COVID-19 causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. Renal system also was impacted and result in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints were linked to PASC. Conclusions: Long COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy as well as more study to address its underlying causes and long-term effects.

Background: Early postoperative airway management after laryngo-tracheal surgery is crucial. Acute respiratory failure due to glottis’ oedema may occur, requiring reintubation. This can prolong ventilatory assistance, jeopardizing the anastomosis. To date, only judicious steroid administration and fluid management are available to avoid more invasive procedures. High-Flow-Oxygen-Therapy(HFOT) is a noninvasive O2 support method providing humidification, warmed air, Positive-End-Expiratory-Pressure(AIRVO2). No data exist about HFOT use to prevent early complications after laryngo-tracheal surgery. Methods: Between Sept.2020-Sept.2022, 107 consecutive patients underwent laryngo-tracheal surgery received HFOT(Group A). Data and long-term results were compared with those of 80 patients operated between Sept.2018-Aug.2020(Group B), when HFOT was not available. All patients were operated in a single center. No pre- or post-operative settings changed, except for HFOT introduction. We analyzed and compared the risk for “delayed” reintubation (unexpected reintubation within the first 24-48 hours after extubating/laryngeal mask removal) in the two groups. Results: No patients reported HFOT-related adverse events. Control group(B) presented “delayed” reintubation in 37% (p= 0.027), Intensive Care Unit admission in 67%(p=0.005) and longer hospital stay(p=0.001) compared to HFOT group(A). Minor complications rate was 3% in both group and overall mortality was 0%. Re-stenosis was described in 4.6% of HFOT group, without a statistically significant difference (p=0.7006). Conclusions: Our study is the first to investigate HFOT use in patients undergoing laryngo-tracheal surgery, potentially representing a consistent innovation in the peri-operative management of these patients. With the limit of a retrospective series, we would suggest HFOT use for preventing post-operative reintubation rate, possibly reducing ICU admission and hospital stay.