Development and Functionalization of a Novel Chitosan-Based Nanosystem for Enhanced Drug Delivery.

Nowadays, infection diseases are one of the most significant threats to humans all around the world. An encouraging strategy for solving this issue and fighting resistant microorganisms is to develop drug carriers for a prolonged release of the antibiotic to the target site. The purpose of this work was to obtain metronidazole-encapsulated chitosan nanoparticles using an ion gelation route and to evaluate their properties. Due to the advantages of the ionic gelation method, the synthesized polymeric nanoparticles can be applied in various fields, especially pharmaceutical and medical. Loading capacity and encapsulation efficiency varFied depending on the amount of antibiotic in each formulation. Physicochemical characterization using scanning electron microscopy revealed a narrow particle size distribution where 90% of chitosan particles were 163.7 nm in size and chitosan-loaded metronidazole nanoparticles were 201.3 nm in size, with a zeta potential value of 36.5 mV. IR spectra revealed characteristic peaks of the drug and polymer nanoparticles. Cell viability assessment revealed that samples have no significant impact on tested cells. Release analysis showed that metronidazole was released from the chitosan matrix for 24 h in a prolonged course, implying that antibiotic-encapsulated polymer nanostructures are a promising drug delivery system to prevent or to treat various diseases. It is desirable to obtain new formulations based on drugs encapsulated in nanoparticles through different preparation methods, with reduced cytotoxic potential, in order to improve the therapeutic effect through sustained and prolonged release mechanisms of the drug correlated with the reduction of adverse effects.

Understanding How Minerals Contribute to Optimal Immune Function.

Sufficient mineral supply is vital not only for the innate immune system but also for the components of the adaptive immune defense, which encompass defense mechanisms against pathogens and the delicate balance of pro- and anti-inflammatory regulation in the long term. Generally, a well-balanced diet is capable of providing the necessary minerals to support the immune system. Nevertheless, specific vulnerable populations should be cautious about obtaining adequate amounts of minerals such as magnesium, zinc, copper, iron, and selenium. Inadequate levels of these minerals can temporarily impair immune competence and disrupt the long-term regulation of systemic inflammation. Therefore, comprehending the mechanisms and sources of these minerals is crucial. In exceptional circumstances, mineral deficiencies may necessitate supplementation; however, excessive intake of supplements can have adverse effects on the immune system and should be avoided. Consequently, any supplementation should be approved by medical professionals and administered in recommended doses. This review emphasizes the crucial significance of minerals in promoting optimal functioning of the immune system. It investigates the indispensable minerals required for immune system function and the regulation of inflammation. Moreover, it delves into the significance of maintaining an optimized intake of minerals from a nutritional standpoint.

Post-Coronary Artery Bypass Grafting Outcomes of Patients with/without Type-2 Diabetes Mellitus and Chronic Kidney Disease Treated with SGLT2 Inhibitor Dapagliflozin: A Single-Center Experience Analysis.

INTRODUCTION: Increasingly, SGLT2 inhibitors save patients with heart failure and comorbidities such as type-2 diabetes mellitus (T2DM) and chronic kidney disease (CKD); the inhibition of sodium-glucose cotransporter 2 (SGLT2) was first studied in patients with diabetes as a solution to lower glucose levels by preventing glucose reabsorption and facilitating its elimination; in the process, researchers took notice of how SGLT2 inhibitors also seemed to have beneficial cardiovascular effects in patients with both diabetes and cardiovascular disease. AIM: Our single-center prospective study assesses outcomes of post-coronary artery bypass grafting (CABG) rehabilitation and SLGT2 inhibition in CABG patients with/without T2DM and with/without CKD. MATERIALS AND METHODS: One hundred twenty consecutive patients undergoing CABG were included in the analysis. Patients were divided into four subgroups: diabetes patients with chronic kidney disease (T2DM + CKD), diabetes patients without chronic kidney disease (T2DM-CKD), prediabetes patients with chronic kidney disease (PreD+CKD), and prediabetes patients without chronic kidney disease (PreD-CKD). Echocardiographic and laboratory investigations post-surgery (phase I) and 6 months later (phase II) included markers for cardiac ischemia, glycemic status, and renal function, and metabolic equivalents were investigated. RESULTS: One hundred twenty patients participated, mostly men, overweight/obese, hypertensive, smokers; 65 had T2DM (18 with CKD), and 55 were prediabetic (17 with CKD). The mean ejection fraction increased by 8.43% overall but significantly more in the prediabetes group compared to the T2DM group (10.14% vs. 6.98%, p < 0.05). Overall, mean heart-type fatty-acid-binding protein (H-FABP) levels returned to normal levels, dropping from 68.40 ng/mL to 4.82 ng/mL (p = 0.000), and troponin data were more nuanced relative to an overall, strongly significant decrease of 44,458 ng/L (p = 0.000). Troponin levels in patients with CKD dropped more, both in the presence of T2DM (by 82,500 ng/L, p = 0.000) and in patients without T2DM (by 73,294 ng/L, p = 0.047). As expected, the overall glycated hemoglobin (HbA1c) levels improved significantly in those with prediabetes (from 6.54% to 5.55%, p = 0.000); on the other hand, the mean HbA1c changed from 7.06% to 6.06% (p = 0.000) in T2DM, and the presence or absence of CKD did not seem to make any difference: T2DM+CKD 7.01-6.08% (p = 0.000), T2DM-CKD 7.08-6.04% (p = 0.000), PreD+CKD 5.66-4.98% (p = 0.014), and PreD-CKD 6.03-4.94% (p = 0.00). Compared to an overall gain of 11.51, the GFRs of patients with CKD improved by 18.93 (68.15-87.07%, p = 0.000) in the presence of established diabetes and 14.89 (64.75-79.64%, p = 0.000) in the prediabetes group. CONCLUSIONS: Regarding the patients' cardiac statuses, the results from our single-center analysis revealed a significant decrease in ischemic risk (H-FABP and hs-cTnI levels) with improvements in mean ejection fraction, glycemic status, and renal function in patients post-CABG with/without T2DM, with/without CKD, and with SGLT2 inhibitor dapagliflozin treatment while undergoing cardiac rehabilitation.

Automated Retinal Vessel Analysis Based on Fundus Photographs as a Predictor for Non-Ophthalmic Diseases-Evolution and Perspectives.

The study of retinal vessels in relation to cardiovascular risk has a long history. The advent of a dedicated tool based on digital imaging, i.e., the retinal vessel analyzer, and also other software such as Integrative Vessel Analysis (IVAN), Singapore I Vessel Assessment (SIVA), and Vascular Assessment and Measurement Platform for Images of the Retina (VAMPIRE), has led to the accumulation of a formidable body of evidence regarding the prognostic value of retinal vessel analysis (RVA) for cardiovascular and cerebrovascular disease (including arterial hypertension in children). There is also the potential to monitor the response of retinal vessels to therapies such as physical activity or bariatric surgery. The dynamic vessel analyzer (DVA) remains a unique way of studying neurovascular coupling, helping to understand the pathogenesis of cerebrovascular and neurodegenerative conditions and also being complementary to techniques that measure macrovascular dysfunction. Beyond cardiovascular disease, retinal vessel analysis has shown associations with and prognostic value for neurological conditions, inflammation, kidney function, and respiratory disease. Artificial intelligence (AI) (represented by algorithms such as QUantitative Analysis of Retinal vessel Topology and siZe (QUARTZ), SIVA-DLS (SIVA-deep learning system), and many others) seems efficient in extracting information from fundus photographs, providing prognoses of various general conditions with unprecedented predictive value. The future challenges will be integrating RVA and other qualitative and quantitative risk factors in a unique, comprehensive prediction tool, certainly powered by AI, while building the much-needed acceptance for such an approach inside the medical community and reducing the "black box" effect, possibly by means of saliency maps.

Current and Emerging Approaches for Spine Tumor Treatment.

Spine tumors represent a significant social and medical problem, affecting the quality of life of thousands of patients and imposing a burden on healthcare systems worldwide. Encompassing a wide range of diseases, spine tumors require prompt multidisciplinary treatment strategies, being mainly approached through chemotherapy, radiotherapy, and surgical interventions, either alone or in various combinations. However, these conventional tactics exhibit a series of drawbacks (e.g., multidrug resistance, tumor recurrence, systemic adverse effects, invasiveness, formation of large bone defects) which limit their application and efficacy. Therefore, recent research focused on finding better treatment alternatives by utilizing modern technologies to overcome the challenges associated with conventional treatments. In this context, the present paper aims to describe the types of spine tumors and the most common current treatment alternatives, further detailing the recent developments in anticancer nanoformulations, personalized implants, and enhanced surgical techniques.

Microvesicles and Microvesicle-Associated microRNAs Reflect Glioblastoma Regression: Microvesicle-Associated miR-625-5p Has Biomarker Potential.

Glioblastoma (GB) is the most aggressive and recurrent form of brain cancer in adults. We hypothesized that the identification of biomarkers such as certain microRNAs (miRNAs) and the circulating microvesicles (MVs) that transport them could be key to establishing GB progression, recurrence and therapeutic response. For this purpose, circulating MVs were isolated from the plasma of GB patients (before and after surgery) and of healthy subjects and characterized by flow cytometry. OpenArray profiling and the individual quantification of selected miRNAs in plasma and MVs was performed, followed by target genes' prediction and in silico survival analysis. It was found that MVs' parameters (number, EGFRvIII and EpCAM) decreased after the surgical resection of GB tumors, but the inter-patient variability was high. The expression of miR-106b-5p, miR-486-3p, miR-766-3p and miR-30d-5p in GB patients' MVs was restored to control-like levels after surgery: miR-106b-5p, miR-486-3p and miR-766-3p were upregulated, while miR-30d-5p levels were downregulated after surgical resection. MiR-625-5p was only identified in MVs isolated from GB patients before surgery and was not detected in plasma. Target prediction and pathway analysis showed that the selected miRNAs regulate genes involved in cancer pathways, including glioma. In conclusion, miR-625-5p shows potential as a biomarker for GB regression or recurrence, but further in-depth studies are needed.

Recent Advances in Managing Spinal Intervertebral Discs Degeneration.

Low back pain (LBP) represents a frequent and debilitating condition affecting a large part of the global population and posing a worldwide health and economic burden. The major cause of LBP is intervertebral disc degeneration (IDD), a complex disease that can further aggravate and give rise to severe spine problems. As most of the current treatments for IDD either only alleviate the associated symptoms or expose patients to the risk of intraoperative and postoperative complications, there is a pressing need to develop better therapeutic strategies. In this respect, the present paper first describes the pathogenesis and etiology of IDD to set the framework for what has to be combated to restore the normal state of intervertebral discs (IVDs), then further elaborates on the recent advances in managing IDD. Specifically, there are reviewed bioactive compounds and growth factors that have shown promising potential against underlying factors of IDD, cell-based therapies for IVD regeneration, biomimetic artificial IVDs, and several other emerging IDD therapeutic options (e.g., exosomes, RNA approaches, and artificial intelligence).

Novel Strategies for Spinal Cord Regeneration.

A spinal cord injury (SCI) is one of the most devastating lesions, as it can damage the continuity and conductivity of the central nervous system, resulting in complex pathophysiology. Encouraged by the advances in nanotechnology, stem cell biology, and materials science, researchers have proposed various interdisciplinary approaches for spinal cord regeneration. In this respect, the present review aims to explore the most recent developments in SCI treatment and spinal cord repair. Specifically, it briefly describes the characteristics of SCIs, followed by an extensive discussion on newly developed nanocarriers (e.g., metal-based, polymer-based, liposomes) for spinal cord delivery, relevant biomolecules (e.g., growth factors, exosomes) for SCI treatment, innovative cell therapies, and novel natural and synthetic biomaterial scaffolds for spinal cord regeneration.

Traumatic subaxial cervical spine injury - Improving initial evaluation through correlation of diffusion tensor imaging and subaxial cervical spine injury classification SLIC score.

BACKGROUND: Traumatic injury to spine and spinal cord represents a devastating condition, with a huge risk for permanent severe disabilities. Predicting the long-term outcome in this type of trauma is a very difficult task being under the influence of a wide spectrum of biomechanical and pathophysiological factors. The advent of magnetic resonance imaging (MRI) structural evaluation of the spinal cord brought critical supplementary data in the initial evaluation of these cases. Although edema and hemorrhage proved to be valuable in predicting the outcome, there is a well-documented discrepancy between MRI findings and clinical status. METHODS: We performed diffusion tensor imaging (DTI) MR in 22 symptomatic patients with traumatic cervical spine injuries (mean age 49.6 ± 16, range from 17 to 74 years, 20 males and 2 females). DTI parameters were computed in 15 patients. Regional apparent diffusion coefficient, fractional anisotropy (FA), and fiber length (FL) were calculated in the region of interest defined as the region of maximum structural MR alterations and in the normal cord (above or below the level of the injury). The values for normal and pathological cord were compared. The clinical deficit was assessed with ASIA and subaxial cervical spine injury classification (SLIC) scores. We looked at the correlation between the DTI measures and clinical scores. RESULTS: There is a highly significant difference between normal and pathological spinal cord for all DTI properties measured. There is also a strong correlation between DTI measures and SLIC clinical score, especially for FA. Significant results were obtained for CDA and FL as well although with lesser statistical power. CONCLUSION: Our results suggest that DTI measures, especially FA, represent a strong indicator of the severity of the traumatic cervical cord injury. It correlates very well with SLCI score and can be used as an additional confirmation of the real degree of level lesioning and as a prognostic factor for the neurological outcome regardless of the choice of treatment.

Third-Generation Cephalosporin-Loaded Chitosan Used to Limit Microorganisms Resistance.

From their discovery, antibiotics have significantly improved clinical treatments of infections, thus leading to diminishing morbidity and mortality in critical care patients, as well as surgical, transplant and other types of medical procedures. In contemporary medicine, a significant debate regarding the development of multi-drug resistance involves all types of pathogens, especially in acute care hospitals due to suboptimal or inappropriate therapy. The possibility of nanotechnology using nanoparticles as matrices to encapsulate a lot of active molecules should increase drug efficacy, limit adverse effects and be an alternative helping to combat antibiotic resistance. The major aim of this study was to obtain and to analyze physico-chemical features of chitosan used as a drug-delivery system in order to stop the antibiotic resistance of different pathogens. It is well known that World Health Organization stated that multidrug resistance is one of the most important health threats worldwide. In last few years, nano-medicine emerged as an improved therapy to combat antibiotic-resistant infections agents. This work relies on enhancement of the antimicrobial efficiency of ceftriaxone against gram(+) and gram(-) bacteria by antibiotic encapsulation into chitosan nanoparticles. Physicochemical features of ceftriaxone-loaded polymer nanoparticles were investigated by particle size distribution and zeta potential, Fourier-transform infrared spectroscopy (FTIR), Thermal Gravimetric Analysis (TG/TGA), Scanning Electron Microscopy (SEM) characteristics techniques. The obtained results revealed an average particle size of 250 nm and a zeta potential value of 38.5 mV. The release profile indicates an incipient drug deliverance of almost 15%, after 2 h of approximately 83%, followed by a slowed drug release up to 24 h. Characteristics peaks of chitosan were confirmed by FTIR spectra indicating a similar structure in the case of ceftriaxone-loaded chitosan nanoparticles. A good encapsulation of the antibiotic into chitosan nanoparticles was also provided by thermo-gravimetric analysis. Morphological characteristics shown by SEM micrographs exhibit spherical nanoparticles of 30-250 nm in size with agglomerated architectures. Chitosan, a natural polymer which is used to load different drugs, provides sustained and prolonged release of antibiotics at a specific target by possessing antimicrobial activity against gram(+) and gram(-) bacteria. In this research, ceftriaxone-loaded chitosan nanoparticles were investigated as a carrier in antibiotic delivery.

Protection measures against SARS-CoV-2 infection for cytopathology and histopathology laboratories personnel: practical recommendations.

In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, healthcare workers are at high risk to be infected with this new coronavirus, particularly when they handle not only patients, but also their body fluids. In Romania, even though the protective measures to be used by medical staff in emergency departments, clinical departments, radiology departments, clinical laboratories and morgues services are well known, there is little information about the protection of medical staff in the laboratories of cytopathology and histopathology. In this article, we will discuss the transmission routes of the new coronavirus, the surfaces it could contaminate in a hospital, as well as the modalities of its inactivation. We will present some guidelines for preparing the pathology departments to face the pandemic situation like the present one. Also, we will point out some possible recommendations/suggestions for protective measures to be taken by laboratory staff during the cytological and histopathological procedures when they manipulate body fluids or surgical samples of patients with suspected or confirmed coronavirus disease 2019 (COVID-19). Laboratory personnel should be aware that any body fluid or surgical specimen that arrives in the laboratory may contain SARS-CoV-2 and, as such, they should act after new working procedures. We recommend restraint from performing extemporaneous examination (smear and frozen section) and cytopathological examination in laboratories that do not have adequate condition for handling and processing Hazard Group 3 (HG3) pathogens, as SARS-CoV-2. Also, laboratory personnel should pay attention to instruments, technical equipment, or environmental surfaces as these also can be contaminated with the new coronavirus.

A Functional Approach to Posttraumatic Salivary Fistula Treatment: The Use of Botulinum Toxin.

This manuscript highlights key aspects regarding the practical use of botulinum toxin for the conservative nonsurgical treatment of a rarely encountered, but significant posttraumatic complication-the parotid salivary fistula. It adds information to the scarce existing literature on the subject. The authors outline the main differences between postoperative and trauma-related parotid injury regarding salivary fistula treatment. A total of 6 patients with trauma-related salivary fistulas have been treated by Abobotulinum toxin A injections over the course of 5 years. The technique is detailed, describing the doses used in the presence of parenchyma and duct injuries, the location and number of injection points in relation to the wound pattern. The results were favorable, leading to the healing of the salivary fistulas in all patients, with 1 injection session, without additional conservative treatment. In our experience, the use of botulinum toxin is of great benefit for treating salivary fistulas in a traumatic context.