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Numerous research projects focused on the management of acute pulmonary hypertension as Coronavirus Disease 2019 (COVID-19) might lead to hypoxia-induced pulmonary vasoconstriction related to acute respiratory distress syndrome. For that reason, inhalative therapeutic options have been the subject of several clinical trials. In this experimental study, we aimed to examine the hemodynamic impact of the inhalation of the SIN-1A formulation (N-nitroso-N-morpholino-amino-acetonitrile, the unstable active metabolite of molsidomine, stabilized by a cyclodextrin derivative) in a porcine model of acute pulmonary hypertension. Landrace pigs were divided into the following experimental groups: iNO (inhaled nitric oxide, n = 3), SIN-1A-5 (5 mg, n = 3), and SIN-1A-10 (10 mg, n = 3). Parallel insertion of a PiCCO system and a pulmonary artery catheter (Swan-Ganz) was performed for continuous hemodynamic monitoring. The impact of iNO (15 min) and SIN-1A inhalation (30 min) was investigated under physiologic conditions and U46619-induced acute pulmonary hypertension. Mean pulmonary arterial pressure (PAP) was reduced transiently by both substances. SIN-1A-10 had a comparable impact compared to iNO after U46619-induced pulmonary hypertension. PAP and PVR decreased significantly (changes in PAP: −30.1% iNO, −22.1% SIN-1A-5, −31.2% SIN-1A-10). While iNO therapy did not alter the mean arterial pressure (MAP) and systemic vascular resistance (SVR), SIN-1A administration resulted in decreased MAP and SVR values. Consequently, the PVR/SVR ratio was markedly reduced in the iNO group, while SIN-1A did not alter this parameter. The pulmonary vasodilatory impact of inhaled SIN-1A was shown to be dose-dependent. A larger dose of SIN-1A (10 mg) resulted in decreased PAP and PVR in a similar manner to the gold standard iNO therapy. Inhalation of the nebulized solution of the new SIN-1A formulation (stabilized by a cyclodextrin derivative) might be a valuable, effective option where iNO therapy is not available due to dosing difficulties or availability. [ABSTRACT FROM AUTHOR]

The manipulation of droplets plays a vital role in biomedicine, chemistry, and hydromechanics, especially in microfluidics. Magnetic droplet manipulation has emerged as a prominent and advanced technique in comparison to other modes such as dielectric infiltration, optical radiation, and surface acoustic waves. Its notable progress is attributed to several advantages, including excellent biocompatibility, remote and non-contact control, and instantaneous response. This review provides a comprehensive overview of recent developments in magnetic droplet manipulation and its applications within the biomedical field. Firstly, the discussion involves an examination of the distinctive features associated with droplet manipulation based on both permanent magnet and electromagnet principles, along with a thorough exploration of the influencing factors impacting magnetic droplet manipulation. Additionally, an in-depth review of magnetic actuation mechanisms and various droplet manipulation methods is presented. Furthermore, the article elucidates the biomedical applications of magnetic droplet manipulation, particularly its role in diagnostic assays, drug discovery, and cell culture. Finally, the highlights and challenges of magnetic droplet manipulation in biomedical applications are described in detail. [ABSTRACT FROM AUTHOR]

Heart failure (HF) with preserved ejection fraction (HFpEF) is an increasingly frequent form and is estimated to be the dominant form of HF. On the other hand, HFpEF is a syndrome with systemic involvement, and it is characterized by multiple cardiac and extracardiac pathophysiological alterations. The increasing prevalence is currently reaching epidemic levels, thereby making HFpEF one of the greatest challenges facing cardiovascular medicine today. Compared to HF with reduced ejection fraction (HFrEF), the medical attitude in the case of HFpEF was a relaxed one towards the disease, despite the fact that it is much more complex, with many problems related to the identification of physiopathogenetic mechanisms and optimal methods of treatment. The current medical challenge is to develop effective therapeutic strategies, because patients suffering from HFpEF have symptoms and quality of life comparable to those with reduced ejection fraction, but the specific medication for HFrEF is ineffective in this situation; for this, we must first understand the pathological mechanisms in detail and correlate them with the clinical presentation. Another important aspect of HFpEF is the diversity of patients that can be identified under the umbrella of this syndrome. Thus, before being able to test and develop effective therapies, we must succeed in grouping patients into several categories, called phenotypes, depending on the pathological pathways and clinical features. This narrative review critiques issues related to the definition, etiology, clinical features, and pathophysiology of HFpEF. We tried to describe in as much detail as possible the clinical and biological phenotypes recognized in the literature in order to better understand the current therapeutic approach and the reason for the limited effectiveness. We have also highlighted possible pathological pathways that can be targeted by the latest research in this field. [ABSTRACT FROM AUTHOR]

Right ventricular failure (RFV) is a potential complication following cardio-thoracic surgery, with an incidence ranging from 0.1% to 30%. The increase in pulmonary vascular resistance (PVR) is one of the main triggers of perioperative RVF. Inhaled pulmonary vasodilators (IPVs) can reduce PVR and improve right ventricular function with minimal systemic effects. This narrative review aims to assess the efficacy of inhaled nitric oxide and inhaled prostacyclins for the treatment of perioperative RVF. The literature, although statistically limited, supports the clinical similarity between them. However, it failed to demonstrate a clear benefit from the pre-emptive use of inhaled nitric oxide in patients undergoing left ventricular assist device implantation or early administration during heart-lung transplants. Additional concerns are related to cost safety and IPV use in pathologies associated with pulmonary venous congestion. The largest ongoing randomized controlled trial on adults (INSPIRE-FLO) is addressing whether inhaled Epoprostenol and inhaled nitric oxide are similar in preventing RVF after heart transplants and left ventricular assist device placement, and whether they are similar in preventing primary graft dysfunction after lung transplants. The preliminary analysis supports their equivalence. Several key points may be achieved by the present narrative review. When RVF occurs in the setting of elevated PVR, IPV should be the preferred initial treatment and they should be preventively used in patients at high risk of postoperative RVF. If severe refractory postoperative RVF occurs, IPVs should be combined with complementary pharmacology (inotropes and inodilators). If unsuccessful, right ventricular mechanical support should be established. [ABSTRACT FROM AUTHOR]

With the increase in the use of Internet interconnected systems, security has become of utmost importance. One key element to guarantee an adequate level of security is being able to detect the threat as soon as possible, decreasing the risk of consequences derived from those actions. In this paper, a new metric for early detection system evaluation that takes into account the delay in detection is defined. Time aware F-score (TaF) takes into account the number of items or individual elements processed to determine if an element is an anomaly or if it is not relevant to be detected. These results are validated by means of a dual approach to cybersecurity, Operative System (OS) scan attack as part of systems and network security and the detection of depression in social media networks as part of the protection of users. Also, different approaches, oriented towards studying the impact of single item selection, are applied to final decisions. This study allows to establish that nitems selection method is usually the best option for early detection systems. TaF metric provides, as well, an adequate alternative for time sensitive detection evaluation. [ABSTRACT FROM AUTHOR]

Brown seaweed is a promising source of polysaccharides and phenolics with industrial utility. This work reports the development of a green enzyme-assisted extraction method for simultaneously extracting polysaccharides and phenolics from the brown seaweed Padina gymnospora. Different enzymes (Cellulast, Pectinex, and Alcalase), individually and in combination, were investigated, with Alcalase alone showing the highest efficiency for the simultaneous extraction of polysaccharides and phenolics. Yields from Alcalase-assisted aqueous extraction were higher than those obtained using either water alone or conventional ethanol extraction. Alcalase-assisted extraction was subsequently optimized using a response surface methodology to maximize compound recovery. Maximal polysaccharide and phenolic recovery was obtained under the following extraction conditions: a water-to-sample ratio of 61.31 mL/g, enzyme loading of 0.32%, temperature of 60.5 °C, and extraction time of 1.95 h. The extract was then fractionated to obtain alginate-, fucoidan-, and phenolic-rich fractions. Fractions exhibited potent 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity with IC50 values of 140.55 µg/mL, 126.21 µg/mL, and 48.17 µg/mL, respectively, which were higher than those obtained from conventional extraction methods. The current work shows that bioactive polysaccharides and phenolics can be obtained together in high yield through a single aqueous-only green and efficient Alcalase-assisted extraction. [ABSTRACT FROM AUTHOR]

Purpose: Despite its rich vascularity, metastasis (MTS) to the thyroid tissue is unusual, ranging from 1 to 3%. This entity is not usually considered as differential diagnosis and is not included in the upfront approach in patients with thyroid nodules. Once diagnosed, treatment is controversial. The aim of this study was to evaluate diagnosis, treatment, and outcome at the end of follow-up in patients with a diagnosis of MTS to the thyroid., Methods: A retrospective multicenter study was designed from 1985 to 2022; 29 patients with MTS to the thyroid gland were included in the analysis., Results: Clinical presentation included the presence of a nodular goiter (65.5%), compression symptoms (17.2%), diffuse goiter (10.3%), and suspicious lymph nodes in the neck (7%). Primary tumor sites were: kidney (44.8%), breast (24.1%), lung (13.8%), neuroendocrine system (6.9%), colon (3.4%), cervix (3.4%), and ovary (3.4%). In 18/23 patients, suspicious ultrasound criteria for malignancy were described. Preoperative diagnosis was made in 23/27 patients by FNA and confirmed in 18 cases by immunohistochemistry. Seventeen patients underwent surgery. At the end of the follow-up, 19 patients had died of oncological disease, and six were alive (2/6 disease-free with isolated intrathyroidal MTS)., Conclusion: Renal carcinoma was the tumor that most frequently metastasized to the thyroid gland. Immunodiagnosis was a very useful tool for etiological confirmation. Patients with MTS to the thyroid gland as a unique site had a more favorable course compared to patients with multiple metastatic sites. Finally, outcomes and prognosis essentially depended on the biology of the primary tumor., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)