Parenteral Anticoagulation at First Medical Contact Improves Infarct Related Artery Patency in STEMI.

(1) Background: Acute ST-segment elevation myocardial infarction (STEMI) remains one of the main morbidity and mortality contributors worldwide. Its main treatment, primary percutaneous coronary intervention (pPCI), can only be performed with a high anticoagulation regimen, usually with heparin. There is still not enough evidence regarding the timing of heparin administration. (2) Methods: We conducted a multicenter observational study of 614 consecutive STEMI patients treated between 2017 and 2019. We split the population in two groups: one that received heparin at the first medical contact, as early as possible, and the second group that received heparin at the PCI capable center or in the cath lab. (3) Results: There was a significantly higher rate of infarct-related artery (IRA) patency at the time of the coronary angiogram in the pre-transfer heparin group than in the on-site heparin group, 44.7% vs. 37.3%, p = 0.042. Also, the early heparin group received shorter and wider stents. There was no difference in bleeding rates or in the in-hospital and two-year mortality rates. (4) Conclusions: Early administration of heparin leads to a higher rate of reperfusion in the IRA, before pPCI, with significant related benefits, such as better stent implantation parameters, without increased bleeding rates.

Peptide-functionalized chitosan-based microcapsules for dual active targeted treatment of lung infections.

Lung infections, such as: pneumonia, chronic obstructive cystic fibrosis, tuberculosis are generally caused by viruses, bacteria and fungi. As these infections are very difficult to treat, new therapeutic approaches are investigated in order to maximize the efficiency of the treatment and to reduce the major complications that can occur. The main objective of this study was focused on the preparation of drug-loaded peptides-functionalized microcapsules, obtained by a double emulsion, based on carboxylated chitosan (CMCS), poly(vinyl alcohol) (PVA) and an activator [4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride] (DMT-MM), for the dual active targeting and treatment of pulmonary infections. The microcapsules were functionalized on the surface with both CGSPGWVRC and indolicidin (IN) peptides, as effective ligands for the active targeting of both alveolar capillary endothelial cells and bacterial cells. FTIR spectroscopy confirmed the formation of ester and amide bonds into the structure of prepared microcapsules. Microcapsules diameter varied between 893 and 965 nm. The swelling degree in PBS, at pH 7.4, ranged between 1760 %- 2100 %. All the analyzed samples showed hemolysis degrees lower than 2 %, which demonstrated their non-hemolytic character. Evaluation of the impact of microcapsules on WI-38 normal human lung cells and RAW 264.7 mouse macrophages revealed a non-toxic or slightly cytotoxic effect. Internalization assay proved that microcapsules were localized at intracellular level.

The Prognostic Value of Platelet-Lymphocyte Ratio, Neutrophil-Lymphocyte Ratio, and Monocyte-Lymphocyte Ratio in Head and Neck Squamous Cell Carcinoma (HNSCC)-A Retrospective Single Center Study and a Literature Review.

INTRODUCTION: Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and pallets-to-lymphocyte ratio (PLR) are currently validated as cheap and accessible biomarkers in different types of solid tumors, including head and neck cancers (HNC). THE PURPOSE OF THE STUDY: To evaluate the possible purposes and biomarker value of NLR, PLR, and MLR recorded pre-treatment (radiotherapy/chemotherapy) in HNC. MATERIALS AND METHODS: From 190 patients with HNC included in the oncology records in the oncology outpatient clinic of the Craiova County Emergency Hospital (from January 2002 to December 2022), 39 cases met the inclusion criteria (squamous cell carcinoma and the possibility to calculate the pre-treatment (chemotherapy/radiotherapy) value of NLR, PLR, and MLR. Overall survival (OS) values were correlated with NLR, PLR, and MLR. RESULTS: The median values for NLR, PLR, and MLR were 6.15 (1.24-69), 200.79 (61.3-1775.0), and 0.53 (0.12-5.5), respectively. In the study, the mean values for NLR, PLR, and MLR of 2.88, 142.97, and 0.36, respectively, were obtained. The median OS in the study group was 11 months (1-120). Although a negative Pearson's correlation was present, the relationship between the variables was only weak, with values of R = 0.07, p = 0.67, R = 0.02, p = 0.31, and R = 0.07, p = 0.62 being related to NLR, PLR, and MLR, respectively, in correlation with OS. The median values of NLR, PLR, and MLR were calculated (1.53, 90.32, and 0.18, respectively) for the HNC cases with pre-treatment values of NLR < 2 and for the HNC cases with NLR values ≥ 6 (23.5, 232.78, and 0.79, respectively). The median OS for cases with NLR < 2 and NLR ≥ 6 were 17.4 and 13 months, respectively. CONCLUSIONS: The comparative analysis of the data highlights a benefit to OS for cases low values of NLR. The role of not only borderline NLR values (between 2 and 6) as a prognostic marker in HNSCC but also the inclusion of PLR and MLR in a prognostic score must also be defined in the future. Prospective studies with more uniformly selected inclusion criteria could demonstrate the value of pre-treatment NLR, PLR, and MLR for treatment stratification through the intensification or de-escalation of non-surgical curative treatment in HNSCC.

Lung cancer and type 2 diabetes experience in Dolj County (southwest region of Romania) - a clinical, bioclinical and pathological study.

BACKGROUND AND AIM: Type 2 diabetes (T2D) and cancer, the most important public health problems nowadays, and the mechanisms between the presence of diabetes and the development of malignancies remain unclear. The leading cause of cancer death in 2020 is attributed to lung cancer. This study aimed to highlight the impact of the association of these two diseases and the predominant histopathological type of lung cancer in the selected group, glycemic imbalance, and information about the course and outlook for these patients. PATIENTS, MATERIALS AND METHODS: The authors proposed a case-control 10-year period study, between 2007 and 2017, of two groups of patients diagnosed with T2D and lung cancer who underwent hospitalization at the Clinic of Medical Oncology, Emergency County Hospital, Craiova, Romania. RESULTS: Our study showed a higher incidence of lung adenocarcinoma in patients diagnosed with T2D. The inflammatory syndrome is more pronounced in the diabetic group, which is supported by correlations between lactate dehydrogenase (LDH), albumin, and hemoglobin levels. CONCLUSIONS: The duration of cancer treatment in lung cancer and the survival rate is strongly influenced by the presence of diabetes as a concomitant disease.

Head and Neck Low Grade Chondrosarcoma-A Rare Entity.

Chondrosarcoma represents approximately 0.1% of all neoplasms of the head and neck and is considered a rare disease with a relatively good prognosis. The 5-year overall survival (OS) rate is estimated at 70-80%, being considered a disease with a low growth rate. Approximately 13% of all cases of chondrosarcoma are located in the region of the head and neck. We present the case of a 30-year-old patient without a medical history who reported dysphagia, swallowing difficulty, neck mass sensation and dysphonia that started insidiously after an upper respiratory tract infection. Subsequently, the patient was diagnosed with a low-grade glosso-epiglottic region chondrosarcoma and was multimodally treated with surgery followed by chemotherapy and radiotherapy. The radiation treatment was delivered with a Rokus M40 former Soviet Union cobalt machine without any image guidance capabilities. The inability to obtain resection margin information justified an aggressive adjuvant treatment with chemotherapy and radiotherapy. The early loss from the oncological record without recurrence of the disease could be associated in this case with the consequence of a major complication, of which we could assume an aspiration pneumonia secondary to a dysphagia associated with an aggressive multidisciplinary treatment. Large tumor size and positive resection margins (R1 resection) are risk factors that support an intensive adjuvant approach in order to reduce the risk of recurrence, but the low grade of tumor associated with a lower risk of recurrence as well as the adverse events (AE) of adjuvant radiotherapy and chemotherapy justify a more reserved therapeutic approach. Taking into account the longer life expectancy of these patients, it is recommended to use a more conformal irradiation technique in order to reduce doses to radiosensitive structures as well as to omit elective neck irradiation, taking into account the lower risk of lymph node involvement. The lack of guidelines, which include very rare tumors including low grade chondrosarcoma of the head and neck, makes a unified approach difficult, but the data presented in case reports could contribute to choosing the regimen that offers the best therapeutic ratio.

Chemical Profile and Bioactivity Evaluation of Salvia Species from Eastern Europe.

The Salvia genus comprises about 1000 species endowed with medicinal, aromatic, cosmetic, and ornamental applications. Even though the genus is one of the most-studied taxa of the Lamiaceae family, data on the chemical composition and biological properties of certain locally used Salvia species are still scarce. The present work aimed to evaluate the phytochemical profile and antimicrobial, antioxidant, and cytotoxic potential of ten Salvia species that grow in Eastern Europe (e.g., the Republic of Moldova). LC-HRMS/MS metabolite profiling allowed for the annotation of 15 phenolic and organic acids, 18 flavonoids, 19 diterpenes, 5 sesterpenes, and 2 triterpenes. Multivariate analysis (e.g., principal component analysis, hierarchical cluster analysis) revealed that S. austriaca, S. nutans, and S. officinalis formed individual clusters, whereas the remaining species had a similar composition. S. officinalis showed the highest activity against Staphylococcus aureus and Streptococcus pneumoniae (MIC = 0.625 mg/mL). As evaluated in DPPH, ABTS, and FRAP assays, S. officinalis was one of the most potent radical scavenging and metal-reducing agents (CE50 values of 25.33, 8.13, and 21.01 µg/mL, respectively), followed by S. verticillata, S. sclarea, S. kopetdaghensis, S. aethiopis, and S. tesquicola. Pearson correlation analysis revealed strong correlations with rosmarinic acid, luteolin-O-glucuronide, and hydroxybenzoic acid. When the cytotoxic activity was evaluated in human breast carcinoma MCF-7 and MDA-MB-231 cells, no significant reduction in cell viability was observed over the concentrations ranging from 25 and 100 µg/mL. The results confirm the potential use of understudied Salvia species as promising sources of antioxidant compounds for developing novel pharmaceutical, nutraceutical, or cosmeceutical products.

Immunotherapy with PD-1 Inhibitor Nivolumab in Recurrent/Metastatic Platinum Refractory Head and Neck Cancers-Early Experiences from Romania and Literature Review.

Prognosis in recurrent/metastatic head and neck squamous-cell carcinoma (HNSCC) refractory to platinum-based chemotherapy is poor, making therapy optimization a priority. Anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody Nivolumab was approved in such cases. We present the early experience with Nivolumab immunotherapy at three cancer clinics from south and northeast Romania, aiming to describe the main characteristics and outcomes relative to literature reports, and to suggest patient selection criteria. Diagnostic, clinical, biological, therapeutic, and outcomes-related data from January 2020 until March 2023 were analyzed retrospectively. Eighteen patients with platinum refractory HNSCC (85.7% men, median age 58.9) were administered Nivolumab for 1-14 months (median 5.6 months) in addition to other treatments (surgery, radiotherapy, chemotherapy), and monitored for up to 25 months. Median neutrophil-to-lymphocyte ratio (NLR) ranged from 2.72 initially to 6.01 during treatment. Overall survival (OS) was 16 months, and patients who died early had the sharpest NLR increases (13.07/month). There were no severe immune-related adverse events. Lower NLR values and combined intensive chemotherapy, radiotherapy, and immunotherapy were related to better outcomes. To our knowledge, we also report the first two cases of second primary malignancy (SPM) in the head and neck region treated with Nivolumab in Romania (for which the sequential administration of radiotherapy and immunotherapy seems better). The work of other Romanian authors on the role of HPV status in HNC is also discussed. Multi-center trials are needed in order to investigate and confirm these observations.

Cancer and Diabetes: Predictive Factors in Patients with Metabolic Syndrome.

BACKGROUND AND OBJECTIVES: A growing number of epidemiological studies have suggested that diabetes mellitus may increase cancer risk and is implicated in numerous other metabolic and inflammatory disorders. The increase in proinflammatory cytokines plays a major role in insulin resistance and leads to hypoalbuminemia and micro- and macrovascular diabetes complications, including kidney disease and anemia. This study aimed to investigate the utility of carcinoembryonic antigen (CEA), C-reactive protein (CRP), serum albumin level, hemoglobin, and lactate dehydrogenase (LDH) as biomarkers for cancer risk, and the biological implications of diabetes on the evolution and prognosis of oncological patients. MATERIAL AND METHODS: We conducted a retrospective, longitudinal, observational study on a total group of 434 patients, of which 217 were diagnosed with a form of cancer and type two diabetes as a comorbidity, and the other 217 were a control group without diabetes. These patients were admitted to the oncology clinic. In subgroups, the same number of patients was considered, depending on the location of the oncological pathology. Anemia, hypoalbuminemia, elevated lactate dehydrogenase, glycated hemoglobin, and C-reactive protein levels are more pronounced in subjects with type two diabetes and cancer. CONCLUSIONS: The presence of diabetes negatively affects the clinical and biological prognosis of cancer patients.

Narrative Review: Update on the Molecular Diagnosis of Fragile X Syndrome.

The diagnosis and management of fragile X syndrome (FXS) have significantly improved in the last three decades, although the current diagnostic techniques are not yet able to precisely identify the number of repeats, methylation status, level of mosaicism, and/or the presence of AGG interruptions. A high number of repeats (>200) in the fragile X messenger ribonucleoprotein 1 gene (FMR1) results in hypermethylation of promoter and gene silencing. The actual molecular diagnosis is performed using a Southern blot, TP-PCR (Triplet-Repeat PCR), MS-PCR (Methylation-Specific PCR), and MS-MLPA (Methylation-Specific MLPA) with some limitations, with multiple assays being necessary to completely characterise a patient with FXS. The actual gold standard diagnosis uses Southern blot; however, it cannot accurately characterise all cases. Optical genome mapping is a new technology that has also been developed to approach the diagnosis of fragile X syndrome. Long-range sequencing represented by PacBio and Oxford Nanopore has the potential to replace the actual diagnosis and offers a complete characterization of molecular profiles in a single test. The new technologies have improved the diagnosis of fragile X syndrome and revealed unknown aberrations, but they are a long way from being used routinely in clinical practice.

Implications of diabetes in head and neck cancer - A single center real-world data.

Diabetes mellitus (DM) and altered glucose metabolism have been associated with carcinogenesis, but also with prognosis and tolerance to treatment in different types of cancer. Head and neck cancers (HNC), the sixth most common malignancy worldwide, require a multimodal approach, especially in advanced stages and cancer specific treatment is often associated with therapeutic failure and severe toxicities even if it is delivered according to current standards. The aim of the study was to evaluate the clinical, biological and outcomes implications of DM in patients with HNC. The cases diagnosed with HNC associated with DM between January 2008 and December 2016 were selected from the database of the oncology clinic and the oncology outpatient clinic of the Craiova County Hospital. Under the limits of a relatively reduced patient lot of 23 cases, certain particular aspects of these cases are highlighted possibly due to the association of DM with HNC. This category of patients should not be treated differently even if a precaution is necessary due to the increased risk of complications related to treatment. The use of Metformin could bring outcome benefit and the treatment of DM with insulin could be associated with a worst prognostic. The use of poly-chemotherapy regimens (platinum double or triple combination including platinum salts) demonstrates the feasibility of using chemotherapy for these subtypes of patients. A tendency to de-escalate the treatment by omitting radiotherapy for this category of patients should also be noted. Neutrophil to lymphocyte ratio (NLR), a less specific biomarker could be less useful than the Glasgow Prognostic Score (GPS) which can be considered an accessible biomarker. A large percent of sinonasal cancers compared to the data reported in the literature could be also related to DM. Both this possible association and the benefit of Metformin and 5-Flurouracil must be reevaluated in studies in larger groups of patients (Ref. 25). Keywords: diabetes, head and neck cancers, metformin, toxicity, outcomes, chemotherapy.

Compact A15 Frank-Kasper nano-phases at the origin of dislocation loops in face-centred cubic metals.

It is generally considered that the elementary building blocks of defects in face-centred cubic (fcc) metals, e.g., interstitial dumbbells, coalesce directly into ever larger 2D dislocation loops, implying a continuous coarsening process. Here, we reveal that, prior to the formation of dislocation loops, interstitial atoms in fcc metals cluster into compact 3D inclusions of A15 Frank-Kasper phase. After reaching the critical size, A15 nano-phase inclusions act as a source of prismatic or faulted dislocation loops, dependent on the energy landscape of the host material. Using cutting-edge atomistic simulations we demonstrate this scenario in Al, Cu, and Ni. Our results explain the enigmatic 3D cluster structures observed in experiments combining diffuse X-ray scattering and resistivity recovery. Formation of compact nano-phase inclusions in fcc structure, along with previous observations in bcc structure, suggests that the fundamental mechanisms of interstitial defect formation are more complex than historically assumed and require a general revision. Interstitial-mediated formation of compact 3D precipitates can be a generic phenomenon, which should be further explored in systems with different crystallographic lattices.

A novel device and system concept for therapeutic plasma exchange in rats.

INTRODUCTION: Therapeutic plasma exchange (TPE) has been developed more than 100 years ago in an animal model and adapted to humans 30 years later. Since then, the TPE research on animal models is lacking, mainly due to difficulties raised by the scaling of the plasmapheresis unit so that the animal's cardiovascular parameters are not considerably affected. METHODS: The system concept of a novel TPE device with continuous hemodynamic monitoring in small rodent models has been used. RESULTS: A continuum TPE unit for rats has been developed, able to produce up to 95% plasma exchange rate without any TPE-related hemodynamic impairment, monitored up to 35 days after the procedure. CONCLUSION: The TPE unit for rats was able to produce 95% plasma exchange rate in non-anesthetized animals, enabling a full translation of the human TPE into an animal model. The newly developed plasmapheresis unit enable a wide range of more accurate preclinical evaluation, with cardiac parameters monitoring, using small rodents in awaken state.

Amnio acid substitution at position 298 of human glucose-6 phosphatase-α significantly impacts its stability in mammalian cells.

Glucose-6-phosphatase-α (G6Pase-α) catalyzes the hydrolysis of glucose-6-phosphate to glucose and functions as a key regulator in maintaining blood glucose homeostasis. Deficiency in G6Pase-α causes glycogen storage disease 1a (GSD1a), an inherited disorder characterized by life-threatening hypoglycemia and other long-term complications. We have developed a potential mRNA-based therapy for GSD1a and demonstrated that a human G6Pase-α (hG6Pase-α) variant harboring a single serine (S) to cysteine (C) substitution at the amino acid site 298 (S298C) had > twofold increase in protein expression, resulting in improved in vivo efficacy. Here, we sought to investigate the mechanisms contributing to the increased expression of the S298C variant. Mutagenesis of hG6Pase-α identified distinct protein variants at the 298 amino acid position with substantial reduction in protein expression in cultured cells. Kinetic analysis of expression and subcellular localization in mammalian cells, combined with cell-free in vitro translation assays, revealed that altered protein expression stemmed from differences in cellular protein stability rather than biosynthetic rates. Site-specific mutagenesis studies targeting other cysteines of the hG6Pase-α S298C variant suggest the observed improvements in stability are not due to additional disulfide bond formation. The glycosylation at Asparagine (N)-96 is critical in maintaining enzymatic activity and mutations at position 298 mainly affected glycosylated forms of hG6Pase-α. Finally, proteasome inhibition by lactacystin improved expression levels of unstable hG6Pase-α variants. Taken together, these data uncover a critical role for a single amino acid substitution impacting the stability of G6Pase-α and provide insights into the molecular genetics of GSD1a and protein engineering for therapeutic development.

Genotype-Phenotype Correlations in 2q37-Deletion Syndrome: An Update of the Clinical Spectrum and Literature Review.

2q37 microdeletion/deletion syndrome (2q37DS) is one of the most common subtelomeric deletion disorders, caused by a 2q37 deletion of variable size. The syndrome is characterized by a broad and diverse spectrum of clinical findings: characteristic facial dysmorphism, developmental delay/intellectual disability (ID), brachydactyly type E, short stature, obesity, hypotonia in infancy, and abnormal behavior with autism spectrum disorder. Although numerous cases have been described so far, the exact mapping of the genotype and phenotype have not yet been achieved. MATERIALS AND METHODS: In this study we analyzed nine newly diagnosed cases with 2q37 deletion (3 male/6 female, aged between 2 and 30 years old), and followed up at the Iasi Regional Medical Genetics Centre. All patients were tested first with MLPA using combined kits P036/P070 subtelomeric screening mix and follow-up mix P264; after, the deletion size and location were confirmed via CGH-array. We compared our findings with the data of other cases reported in the literature. RESULTS: From nine cases, four had pure 2q37 deletions of variable sizes, and five presented deletion/duplication rearrangements (with chromosomes 2q, 9q, and 11p). In most cases, characteristic phenotypic aspects were observed: 9/9 facial dysmorphism, 8/9 global developmental delay and ID, 6/9 hypotonia, 5/9 behavior disorders, and 8/9 skeletal anomalies-especially brachydactyly type E. Two cases had obesity, one case had craniosynostosis, and four had heart defects. Other features found in our cases included translucent skin and telangiectasias (6/9), and a hump of fat on the upper thorax (5/9). CONCLUSIONS: Our study enriches the literature data by describing new clinical features associated with 2q37 deletion, and possible genotype-phenotype correlations.

The Profile and All-Cause In-Hospital Mortality Dynamics of St-Segment Elevation Myocardial Infarction Patients during the Two Years of the COVID-19 Pandemic.

During the coronavirus pandemic 2019 (COVID-19), some studies showed differences in the profile of subjects presenting with acute coronary syndromes as well as in overall mortality due to the delay of presentation and other complications. The purpose of this study was to compare the profile and outcomes, with emphasis on all-cause in-hospital mortality, of ST-elevation myocardial infarction (STEMI) subjects presenting to the emergency department during the pandemic period compared with a control group from the previous year, 2019. The study enrolled 2011 STEMI cases, which were divided into two groups-pre-pandemic (2019-2020) and pandemic period (2020-2022). Hospital admissions for a STEMI diagnosis sharply decreased during the COVID-19 period by 30.26% during the first year and 25.4% in the second year. This trend was paralleled by a significant increase in all-cause in-hospital mortality: 11.5% in the pandemic period versus 8.1% in the previous year. There was a significant association between SARS-CoV-2 positivity and all-cause in-hospital mortality, but no correlation was found between COVID-19 diagnosis and the type of revascularization. However, the profile of subjects presenting with STEMI did not change over time during the pandemic; their demographic and comorbid characteristics remained similar.

18F-FDG PET/MRI Imaging in a Preclinical Rat Model of Cardiorenal Syndrome-An Exploratory Study.

Cardiorenal syndrome (CRS) denotes the bidirectional interaction of chronic kidney disease and heart failure with an adverse prognosis but with a limited understanding of its pathogenesis. This study correlates biochemical blood markers, histopathological and immunohistochemistry features, and 2-deoxy-2-fluoro-D-glucose positron emission tomography (18F-FDG PET) metabolic data in low-dose doxorubicin-induced heart failure, cardiorenal syndrome, and renocardiac syndrome induced on Wistar male rats. To our knowledge, this is the first study that investigates the underlying mechanisms for CRS progression in rats using 18F-FDG PET. Clinical, metabolic cage monitoring, biochemistry, histopathology, and immunohistochemistry combined with PET/MRI (magnetic resonance imaging) data acquisition at distinct points in the disease progression were employed for this study in order to elucidate the available evidence of organ crosstalk between the heart and kidneys. In our CRS model, we found that chronic treatment with low-dose doxorubicin followed by acute 5/6 nephrectomy incurred the highest mortality among the study groups, while the model for renocardiac syndrome resulted in moderate-to-high mortality. 18F-FDG PET imaging evidenced the doxorubicin cardiotoxicity with vascular alterations, normal kidney development damage, and impaired function. Given the fact that standard clinical markers were insensitive to early renal injury, we believe that the decreasing values of the 18F-FDG PET-derived renal marker across the groups and, compared with their age-matched controls, along with the uniform distribution seen in healthy developing rats, could have a potential diagnostic and prognostic yield in cardiorenal syndrome.

Pulmonary Embolism Risk Assessment Using Blood Copeptin Concentration and Pulmonary Arteries Thrombotic Burden Evaluated by Computer Tomography.

(1) Background: Pulmonary embolism (PE) represents the third most important cardiovascular cause of death after myocardial infarction and stroke. The proper management of this condition is dependent on adequate risk stratification, due to the life-threatening complications of more aggressive therapies such as thrombolysis. Copeptin is a surrogate marker of vasopressin which is found increased in several cardiovascular conditions. The Mastora score is an imagistic evaluation of the degree of pulmonary arteries thrombotic burden based on computed tomography angiography. In this study, we aimed to evaluate the diagnostic and prognostic role of copeptin in patients with acute PE. Furthermore, we analyzed the relationship between copeptin and Mastora score and their role in PE risk profiling. (2) Methods: We conducted a single center prospective study that included 112 patients with PE and 53 healthy volunteers. Clinical and paraclinical parameters, together with plasma levels of copeptin and the Mastora score, were evaluated in all patients after admission. (3) Results: Copeptin levels were significantly increased in PE patients compared with the general population (26.05 vs. 9.5 pmol/L, p < 0.001), while receiver operating characteristic (ROC) analysis revealed an AUC of 0.800 (95% CI 0.728−0.873, p < 0.001). Copeptin directly correlated with the Mastora score (r = 0.535, p = 0.011) and both parameters were strong predictors for adverse clinical events and death. Receiver operating characteristic (ROC) analysis for death within 30 days revealed a copeptin cut-off of 38.36 pmol/L, which presented a specificity of 79.6% and a sensitivity of 88.9%, and a Mastora score cut-off of 82 points, which presented a specificity of 74.8% and a sensitivity of 77.8%. (4) Conclusions: Our results showed that copeptin and the Mastora score are both correlated with adverse cardiovascular events and mortality in PE patients, and this may pave the way for their use in clinical practice, helping physicians to select the best therapeutical management.

Takotsubo Cardiomyopathy and ß-Blocker Poisoning: A Case Report.

ß-blocker poisoning is frequently observed because of its primary use for the treatment of cardiovascular diseases. The management of ß-blocker toxicity is dependent on the cardiovascular response and the severity of presentation. The present study describes the case of a patient with combined drug intoxication, ß-blocker, digoxin, benzodiazepines, acetaminophen and opiates in a suicidal attempt. A 63-year-old female was found somnolent and in a confused state at her residence following intentional poly-drug ingestion. Upon presentation, she was found to be hemodynamically unstable and was thus treated with vasopressors. The toxicological screening performed upon presentation was positive for polydrug ingestion. On day 3, the patient developed chest pain and ST-segment elevation in anterior leads, while transthoracic echocardiographic assessment disclosed a non-dilated left ventricle with moderate dysfunction and akinesia of the apex. Coronary angiogram revealed normal coronary arteries and, subsequently, the diagnosis of Takotsubo cardiomyopathy (TTC) was suspected. Supportive treatment was initiated with favorable evolution and left ventricular ejection fraction normalization. The management of hemodynamic instability with vasopressors should be judiciously administered in the treatment of ß-blocker poisoning, in view of the adverse effects on cardiac functions, including stress cardiomyopathy.

Nanoporous Membranes for the Filtration of Proteins from Biological Fluids: Biocompatibility Tests on Cell Cultures and Suggested Applications for the Treatment of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease has a significant epidemiological and socioeconomic impact, and, unfortunately, the extensive research focused on potential curative therapies has not yet proven to be successful. However, in recent years, important steps have been made in the development and functionalization of nanoporous alumina membranes, which might be of great interest for medical use, including the treatment of neurodegenerative diseases. In this context, the aim of this article is to present the synthesis and biocompatibility testing of a special filtrating nano-membrane, which is planned to be used in an experimental device for Alzheimer's disease treatment. METHODS: Firstly, the alumina nanoporous membrane was synthesized via the two-step anodizing process in oxalic acid-based electrolytes and functionalized via the atomic layer deposition technique. Subsequently, quality control tests (spectrophotometry and potential measurements), toxicity, and biocompatibility tests (cell viability assays) were conducted. RESULTS: The proposed alumina nanoporous membrane proved to be efficient for amyloid-beta filtration according to the permeability studies conducted for 72 h. The proposed membrane has proven to be fully compatible with the tested cell cultures. CONCLUSIONS: The proposed alumina nanoporous membrane model is safe and could be incorporated into implantable devices for further in vivo experiments and might be an efficient therapeutic approach for Alzheimer's disease.

Chemical Composition, Antioxidant and Antiproliferative Activities of Taraxacum officinale Essential Oil.

Taraxacum officinale (TO) has been historically used for medicinal purposes due to its biological activity against specific disorders. To investigate the antioxidant and the antiproliferativepotential of TO essential oil in vitro and in vivo, the chemical composition of the essential oil was analyzed by GC-MS. The in vivo antioxidant capacity was assessed on liver and kidney homogenate samples from mice subjected to acetaminophen-induced oxidative stress and treated with TO essential oil (600 and 12,000 mg/kg BW) for 14 days. The in vitro scavenging activity was assayed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the reducing power methods. The cytotoxic effects against the HeLa cancer cell line were analyzed. The GC-MS analysis showed the presence of 34 compounds, 8 of which were identified as major constituents. The TO essential oil protected mice's liver and kidneys from acetaminophen-induced oxidative stress by enhancing antioxidant enzymes (catalase, superoxide dismutase, and glutathione) and lowering malondialdehyde levels. In vitro, the TO essential oil demonstrated low scavenging activity against DPPH (IC50 = 2.00 ± 0.05 mg/mL) and modest reducing power (EC50 = 0.963 ± 0.006 mg/mL). The growth of the HeLa cells was also reduced by the TO essential oil with an inhibition rate of 83.58% at 95 µg/mL. Current results reveal significant antioxidant and antiproliferative effects in a dose-dependent manner and suggest that Taraxacum officinale essential oil could be useful in formulations for cancer therapy.