Cell therapies for spinal cord injury: a review of the clinical trials and cell-type therapeutic potential.

Spinal cord injury (SCI) is an as yet untreatable neuropathology that causes severe dysfunction and disability. Cell-based therapies hold neuroregenerative and neuroprotective potential, but, although being studied in SCI patients for more than two decades, long-term efficacy and safety remain unproven, and which cell types result in higher neurological and functional recovery remains under debate. In a comprehensive scoping review of 142 reports and registries of SCI cell-based clinical trials, we addressed the current therapeutical trends and critically analysed the strengths and limitations of the studies. Schwann cells, olfactory ensheathing cells (OECs), macrophages and various types of stem cells have been tested, as well as combinations of these and other cells. A comparative analysis between the reported outcomes of each cell type was performed, according to gold-standard efficacy outcome measures like the ASIA impairment scale, motor and sensory scores. Most of the trials were in the early phases of clinical development (phase I/II), involved patients with complete chronic injuries of traumatic aetiology and did not display a randomized comparative control arm. Bone marrow stem cells and OECs were the most commonly tested cells, while open surgery and injection were the main methods of delivering cells into the spinal cord or submeningeal spaces. Transplantation of support cells, such as OECs and Schwann cells, resulted in the highest ASIA Impairment Scale (AIS) grade conversion rates (improvements in ∼40% of transplanted patients), which surpassed the spontaneous improvement rate expected for complete chronic SCI patients within 1 year post-injury (5-20%). Some stem cells, such as peripheral blood-isolated and neural stem cells, offer potential for improving patient recovery. Complementary treatments, particularly post-transplantation rehabilitation regimes, may contribute highly to neurological and functional recovery. However, unbiased comparisons between the tested therapies are difficult to draw, given the great heterogeneity of the design and outcome measures used in the SCI cell-based clinical trials and how these are reported. It is therefore crucial to standardize these trials when aiming for higher value clinical evidence-based conclusions.

Towards optimization of ceftazidime dosing in obese ICU patients: the end of the 'one-size-fits-all' approach?

BACKGROUND: Ceftazidime is commonly used as a key antibiotic against Pseudomonas aeruginosa in critically ill patients. ICU patients have severely altered and variable antibiotic pharmacokinetics, resulting in lower antimicrobial concentrations and potentially poor outcome. Several factors, including obesity and renal function, may influence pharmacokinetics. Thus, the objective of the study was to evaluate the impact of obesity and renal function on ceftazidime plasma concentrations and dosing regimen in ICU patients. METHODS: All consecutive adult patients from six ICUs, treated with continuous ceftazidime infusion and under therapeutic drug monitoring evaluation, were included. Obesity was defined as BMI ≥30 kg/m². Glomerular filtration rate (GFR) was estimated by the Chronic Kidney Disease Epidemiology Collaboration formula. The ceftazidime recommended target for plasma concentrations was between 35 and 80 mg/L. RESULTS: A total of 98 patients (45 obese), with an average weight of 90 (±25) kg, were included. Mean GFR was 84.1 (±40.4) mL/min/1.73 m2. Recommended ceftazidime plasma concentrations were achieved for only 48.0% of patients, with median dosing regimen of 6 g/day. Obese patients had lower ceftazidime plasma concentrations compared with non-obese patients (37.8 versus 56.3 mg/L; P = 0.0042) despite similar dosing regimens (5.83 g/day versus 5.52 g/day, P = 0.2529). Almost all augmented renal clearance patients were underdosed despite ceftazidime dosing of 6.6 (±0.8) g/day. Weight-based ceftazidime dosing seemed to attenuate such obesity-related discrepancies, regardless of GFR. CONCLUSIONS: Obese ICU patients required significantly greater ceftazidime doses to achieve the target range. A tailored dosing regimen may be considered based on weight and GFR. Future prospective studies should be performed to confirm this individualized dosing approach.

Characterization of education, technical practices and attitudes of Portuguese pharmacy technicians towards manipulation of cytotoxic drugs.

Pharmacy professionals that manipulate cytotoxic drugs need to undergo educational programs, adopt the most convenient practices, and use appropriate equipment to avoid, as far as possible, occupational exposure to cytotoxic drugs. The main goal of this work is to characterize the education, technical practices, and attitudes towards cytotoxic drugs, of Portuguese pharmacy technicians. A questionnaire comprising eleven questions deemed pertinent was elaborated and subsequently validated by a pilot test. The anonymous, web-based survey was conducted between December 2022 and January 2023, by graduated pharmacy technicians that had manipulated cytotoxic drugs between 2017 and 2022. A total of 77 pharmacy technicians responded to the survey. Although sixty-six pharmacy technicians (86%) had been trained before beginning to manipulate cytotoxic drugs, the promotion of regular post-admission training by the institutions is sparse - only assumed by 53% of the pharmacy technicians (n = 41). All participants reported using gloves and gown during manipulation and the use of double gloves was common (99%; n = 76). Compliances with the recommended limit time for uninterrupted manipulation activity (82%; n = 63) and systematic double-checking (86%; n = 66) were high, but the regular use of sterile gauze around syringe connection sites 58% (n = 45), was less frequent. None of the surveyed pharmacy technicians used closed-system transfer devices (CSTD) and 41 (53%) of those who used spikes did not thoughtfully use these devices. The implementation of regular training programs in manipulating cytotoxic drugs should be fostered, to promote the more judicious use of engineering controls and transversal adoption of the safest technical practices.

Virtual reality and behaviour management in paediatric dentistry: a systematic review.

BACKGROUND: Virtual reality (VR) has emerged as an innovative tool in medicine and dentistry, improving anxiety and pain management in children. The immersive and interactive environments of VR technology facilitate positive engagement of young patients during dental procedures via distraction, potentially reducing anxiety levels and improving treatment experience. The aim of this review was to provide current evidence-based guidance on the usage of VR in the clinical practice of paediatric dentistry. METHODS: A systematic review was conducted according to the PRISMA guidelines with the following research question using the PICO format: Does VR (I) effectively manage anxiety and pain (O) during a paediatric dental consultation (P) compared to alternative behavioural control techniques (C)? PubMed/Medline®, SCOPUS and Web of Science databases were searched and analysed. RESULTS: A total of 22 randomised control trials were included in this review. These studies have shown that VR is a highly effective method of behaviour management, successfully alleviating pain and anxiety in children during dental treatment, surpassing traditional tools. Selected studies included participants with a large age range and dental procedures varied greatly, from first consultations to infiltration of local anaesthetic and other invasive procedures. VR was mostly used during treatment delivery and different immersive VR techniques were considered. Behaviour, anxiety and pain scales were used to determine efficacy and patient satisfaction. CONCLUSIONS: VR offers an engaging and immersive experience, effectively diverting patients' attention away from the clinical environment, fostering a positive and enjoyable treatment experience. However, it is important to acknowledge the limitations of existing studies and the need for further research to enhance the understanding of VR's full potential in paediatric dentistry.

Dietary polyglycosylated anthocyanins, the smart option? A comprehensive review on their health benefits and technological applications.

Over the years, anthocyanins have emerged as one of the most enthralling groups of natural phenolic compounds and more than 700 distinct structures have already been identified, illustrating the exceptional variety spread in nature. The interest raised around anthocyanins goes way beyond their visually appealing colors and their acknowledged structural and biological properties have fueled intensive research toward their application in different contexts. However, the high susceptibility of monoglycosylated anthocyanins to degradation under certain external conditions might compromise their application. In that regard, polyglycosylated anthocyanins (PGA) might offer an alternative to overcome this issue, owing to their peculiar structure and consequent less predisposition to degradation. The most recent scientific and technological findings concerning PGA and their food sources are thoroughly described and discussed in this comprehensive review. Different issues, including their physical-chemical characteristics, consumption, bioavailability, and biological relevance in the context of different pathologies, are covered in detail, along with the most relevant prospective technological applications. Due to their complex structure and acyl groups, most of the PGA exhibit an overall higher stability than the monoglycosylated ones. Their versatility allows them to act in a wide range of pathologies, either by acting directly in molecular pathways or by modulating the disease environment attributing an added value to their food sources. Their recent usage for technological applications has also been particularly successful in different industry fields including food and smart packaging or in solar energy production systems. Altogether, this review aims to put into perspective the current state and future research on PGA and their food sources.

The Role of Anthocyanins, Deoxyanthocyanins and Pyranoanthocyanins on the Modulation of Tyrosinase Activity: An In Vitro and In Silico Approach.

Tyrosinase is the central enzyme involved in the highly complex process of melanin formation, catalyzing the rate-limiting steps of this biosynthetic pathway. Due to such a preponderant role, it has become a major target in the treatment of undesired skin pigmentation conditions and also in the prevention of enzymatic food browning. Numerous phenolic-based structures from natural sources have been pointed out as potential tyrosinase inhibitors, including anthocyanins. The aim of the present study was to individually assess the tyrosinase inhibitory activity of eight purified compounds with a variable degree of structural complexity: native anthocyanins, deoxyanthocyanins, and pyranoanthocyanins. The latter two, the groups of anthocyanin-related compounds with enhanced stability, were tested for the first time. Compounds 1 to 4 (luteolinidin, deoxymalvidin, cyanidin-, and malvidin-3-O-glucoside) revealed to be the most effective inhibitors, and further kinetic studies suggested their inhibition mechanism to be of a competitive nature. Structure-activity relationships were proposed based on molecular docking studies conducted with mushroom tyrosinase (mTYR) and human tyrosinase-related protein 1 (hTYRP1) crystal structures, providing information about the binding affinity and the different types of interactions established with the enzyme's active center which corroborated the findings of the inhibition and kinetic studies. Overall, these results support the applicability of these compounds as pigmentation modulators.

Exploring the Applications of the Photoprotective Properties of Anthocyanins in Biological Systems.

Due to their physical and chemical characteristics, anthocyanins are amongst the most versatile groups of natural compounds. Such unique signature makes these compounds a focus in several different areas of research. Anthocyanins have well been reported as bioactive compounds in a myriad of health disorders such as cardiovascular diseases, cancer, and obesity, among others, due to their anti-inflammatory, antioxidant, anti-diabetic, anti-bacterial, and anti-proliferative capacities. Such a vast number of action mechanisms may be also due to the number of structurally different anthocyanins plus their related derivatives. In this review, we highlight the recent advances on the potential use of anthocyanins in biological systems with particular focus on their photoprotective properties. Topics such as skin aging and eye degenerative diseases, highly influenced by light, and the action of anthocyanins against such damages will be discussed. Photodynamic Therapy and the potential role of anthocyanins as novel photosensitizers will be also a central theme of this review.

"Clicking" an Ionic Liquid to a Potent Antimicrobial Peptide: On the Route towards Improved Stability.

A covalent conjugate between an antibacterial ionic liquid and an antimicrobial peptide was produced via "click" chemistry, and found to retain the parent peptide's activity against multidrug-resistant clinical isolates of Gram-negative bacteria, and antibiofilm action on a resistant clinical isolate of Klebsiella pneumoniae, while exhibiting much improved stability towards tyrosinase-mediated modifications. This unprecedented communication is a prelude for the promise held by ionic liquids -based approaches as tools to improve the action of bioactive peptides.

CD81 Promotes a Migratory Phenotype in Neuronal-Like Cells.

Tetraspanins, such as CD81, can form lateral associations with each other and with other transmembrane proteins. These interactions may underlie CD81 functions in multiple cellular processes, such as adhesion, morphology, migration, and differentiation. Since CD81's role in neuronal cells' migration has not been established, we here evaluated effects of CD81 on the migratory phenotype of SH-SY5Y neuroblastoma cells. CD81 was found enriched at SH-SY5Y cell's membrane, co-localizing with its interactor filamentous-actin (F-actin) in migratory relevant structures of the leading edge (filopodia, stress fibers, and adhesion sites). CD81 overexpression increased the number of cells with a migratory phenotype, in a potentially phosphatidylinositol 3 kinase (PI3K)-Ak strain transforming (AKT) mediated manner. Indeed, CD81 also co-localized with AKT, a CD81-interactor and actin remodeling agent, at the inner leaflet of the plasma membrane. Pharmacologic inhibition of PI3K, the canonical AKT activator, led both to a decrease in the acquisition of a migratory phenotype and to a redistribution of intracellular CD81 and F-actin into cytoplasmic agglomerates. These findings suggest that in neuronal-like cells CD81 bridges active AKT and actin, promoting the actin remodeling that leads to a motile cell morphology. Further studies on this CD81-mediated mechanism will improve our knowledge on important physiological and pathological processes such as cell migration and differentiation, and tumor metastasis.

Oral Mucositis Management in Children under Cancer Treatment: A Systematic Review.

Children undergoing antineoplastic treatment often present severe side effects due to the dosage and duration of treatments, with oral mucositis emerging as one of the most prevalent and painful inflammatory conditions. There is a growing body of evidence on therapeutic interventions such as cryotherapy, low-level laser therapy, and natural compounds for this condition. The aim of this systematic review was to identify and compare therapies for the management of cancer treatment-induced oral mucositis in pediatric patients. From 2655 articles obtained in initial searches, 39 articles were considered in this systematic review, after applying inclusion/exclusion criteria. Low-level laser therapy, palifermin, honey, and zinc demonstrated reductions in oral mucositis incidence, duration, severity, and pain reported by the patient. Although there are several therapies in place for the prevention and treatment of oral mucositis in children, evidence of their efficacy is still inconclusive to establish accurate clinical protocols.

Dosing Regimen for Cefotaxime Should Be Adapted to the Stage of Renal Dysfunction in Critically Ill Adult Patients-A Retrospective Study.

Cefotaxime administration is recommended in doses of 3-12 g/day in adults with a Glomerular Filtration Rate (GFR) > 5 mL/min. This study aimed to assess the impact of renal function and obesity on cefotaxime concentrations in intensive care unit (ICU) patients. A retrospective cohort study was conducted on consecutive ICU patients receiving continuous cefotaxime infusion between 2020 and 2022 [IRBN992021/CHUSTE]. Doses were not constant; consequently, a concentration-to-dose ratio (C/D) was considered. Statistical analysis was performed to assess the relationship between cefotaxime concentrations, renal function, and obesity. A total of 70 patients, median age 61 years, were included, with no significant difference in cefotaxime concentrations between obese and non-obese patients. However, concentrations varied significantly by GFR, with underdosing prevalent in patients with normal to increased renal function and overdosing in those with severely impaired renal function. Adjustment of cefotaxime dosing according to GFR was associated with improved target attainment. Cefotaxime dosing in critically ill patients should consider renal function, with higher initial doses required in patients with normal to increased GFR and lower doses in those with severely impaired renal function. Therapeutic drug monitoring may aid in optimising dosing regimens. Prospective studies are warranted to validate these findings and inform clinical practice.

Cardiovascular risk assessment using SCORE2 in a population with hypertension - The reality at a primary health care unit.

INTRODUCTION AND OBJECTIVES: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Portugal, thus it is important to identify individuals at risk. Patients with hypertension have an increased risk of adverse cardiovascular (CV) events. The role of LDL cholesterol (LDL-C) in atherosclerotic CVD is well-established. SCORE2, a new CV risk calculation tool, is used to predict the 10-year risk of fatal or non-fatal CVD. The aim of this study was to understand the impact of SCORE2 on CV risk assessment in a population with hypertension from a moderate risk country, compared to the previously used SCORE. METHODS: This observational cross-sectional study analyzed a population census of 3146 patients diagnosed with hypertension without complications (K86). After applying inclusion and exclusion criteria, 654 patients were included. Data from medical records were collected to calculate and compare SCORE and SCORE2 categories and LDL-C targets. RESULTS: Patients were classified into SCORE categories: 188 (28.75%) low, 448 (68.5%) moderate, 17 (2.6%) high and 1 (0.15%) very high risk. Using SCORE2, individuals in the SCORE low risk category were reclassified, requiring new targets: 149 individuals (80%) as low to moderate and 39 (20%) as high risk. These differences became more evident when considering SCORE moderate and high-risk categories, where 358 patients (77%) received a higher CV risk categorization, and therefore a lower LDL-C target. There was a significant increase in individuals failing to meet the target when using SCORE2, compared to SCORE (p<0.001). CONCLUSION: These findings support the importance of CV risk assessment using SCORE2 algorithm in patients with hypertension.

Investigating the correlation between genotype and phenotype in Prader-Willi syndrome: a study of 45 cases from Brazil.

BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder characterized by abnormalities in the 15q11-q13 region. Understanding the correlation between genotype and phenotype in PWS is crucial for improved genetic counseling and prognosis. In this study, we aimed to investigate the correlation between genotype and phenotype in 45 PWS patients who previously underwent methylation-sensitive high-resolution melting (MS-HRM) for diagnosis. RESULTS: We employed methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and Sanger sequencing, along with collecting phenotypic data from the patients for comparison. Among the 45 patients, 29 (64%) exhibited a deletion of 15q11-q13, while the remaining 16 (36%) had uniparental disomy. No statistically significant differences were found in the main signs and symptoms of PWS. However, three clinical features showed significant differences between the groups. Deletion patients had a higher prevalence of myopia than those with uniparental disomy, as well as obstructive sleep apnea and an unusual skill with puzzles. CONCLUSIONS: The diagnostic tests (MS-HRM, MS-MLPA, and Sanger sequencing) yielded positive results, supporting their applicability in PWS diagnosis. The study's findings indicate a general similarity in the genotype-phenotype correlation across genetic subtypes of PWS.

Teaching and training of human resources for genetics and genomics in Brazil.

This manuscript reviewed the state of the art about the teaching and training of human resources for genetics and genomics in Brazil. We presented the national scenario of teaching genetics in medical undergraduate and other health courses. We discussed the training of medical geneticists through medical residency and addressed the training in genetics of physicians from specialties other than genetics. We examined the training of health professionals specializing in genetics through lato sensu and stricto sensu postgraduate programs and presented the proposals for multi-professional residency in genetic counseling and genetics and genomics that are currently the subject of discussion in the country. Finally, we highlighted the importance of training primary health care professionals concerning genetics and genomics for the effective establishment of a line of care for individuals with genetic disorders in the Brazilian Unified Health System. Therefore, we provided a thorough overview of how genetics is (or is not) incorporated into professional training in a comprehensive public healthcare system such as the Brazilian.

Understanding the Role of Mono and Ternary Alkali Metal Salts on CO2 Uptake of MgO Sorbents.

CO2 uptake by MgO-based sorbents at intermediate temperatures is attractive for pre- and post-combustion CO2 capture applications. However, besides the high CO2 uptake potential of these materials (1.1 g CO2 g-1 sorbent), in practice, the realistic CO2 capture is far from that of the theorical values. In this work, the sol-gel method was used to synthetize unsupported and supported MgO sorbents (10% Ca- or 10% Ce- support, mol) that were impregnated with different fractions (15, 25, and 35; % mol) of a NaNO3 single salt or a ternary alkali salt (NaNO3, LiNO3 and KNO3 (18/30/52; % mol)). To understand the role of alkali metal salts (AMSs) in the MgO sorbents' performance, the working and decomposition temperature ranges of AMS under different atmospheres (CO2 and air) were evaluated. The findings show that the CO2 uptake temperature range and maximum uptake (20-500 °C, CO2 atmosphere) of sorbents are correlated. The cyclic CO2 uptake of the most promising sorbents was tested along five carbonation-calcination cycles. For the first and fifth cycles, respectively, the 15 (Na, K, Li)-MgO sorbents showed the highest carrying capacity, i.e., 460-330 mg CO2 g-1 sorbent, while for the 15 (Na, K, Li)-MgO-Ca sorbents, it was 375-275 mg CO2 g-1. However, after the first cycle, the carbonation occurred faster for the 15 (Na, K, Li)-MgO-Ca sorbents, meaning that it can be a path to overpassing carbonation kinetics limitations of the MgO sorbent, making it viable for industrial applications.

Methods of Primary Clinical Prevention of Dental Caries in the Adult Patient: An Integrative Review.

AIM: Preventive approaches to oral health diseases, mainly dental caries, require individual and collective policies. Thus, this review was conducted to identify the primary prevention methods of dental caries in adults to improve oral health at the clinical and community levels. METHODS: This review followed the PICO strategy with the research question: "What are the methods of primary prevention of dental caries, in adults, for improving and maintaining oral health integrating clinical and community-based strategies?" Electronic screening was carried out by two independent reviewers in five databases (MedLine/PubMed, SciELO, Web of Science, Cochrane Library, and LILACS) to find relevant publications between 2015-2022. We applied eligibility criteria for selection of the articles. The following MeSH terms were used: "Primary Prevention"; "Adult"; "Oral Health"; "Dental Caries"; "Fluorides, Topical"; "Fluoride Varnishes"; "Pit and Fissure Sealants"; "Preventive Dentistry". Although the term "Prevention strategy" is not a MeSH descriptor, several correlated terms appeared and were used in the search engines: "Preventative Care", "Disease Prevention, Primary", and "Prevention, Primary". The tool provided by the JBI organization (Joanna Briggs Institute) was used to assess the quality of the included studies. RESULTS: Nine studies were included. Overall, it was found that the main primary prevention methods applied in dentistry in adults are the application of pit and fissure sealants, topical application of fluoride performed in the dental clinic, use of fluoridated toothpaste, mouthwash with chlorhexidine at home, use of xylitol, the recommendation for regular appointments with the dentist, and the need to inform patients about the saliva buffer capacity and adoption of a non-cariogenic diet. For that purpose, preventive policies should be taken to prevent dental caries. These include three major challenges: providing the adult population with more knowledge regarding their oral health, empowering patients through adopting healthy lifestyles, and developing new preventive strategies and awareness campaigns aimed at the adult population to promote proper oral health habits. CONCLUSIONS: A small number of studies were found whose participants were adult patients. There was some consistency regarding primary prevention methods in our studies. However, good quality randomized control studies are still required to define the best intervention strategies for adult caries prevention.

Long-term outcomes of COVID-19 intensive care unit survivors and their family members: a one year follow-up prospective study.

Purpose: To describe the long-term physical, functional and mental status of COVID-19 intensive care unit (ICU) patients and their family members 1 year after ICU discharge. Methods: We performed a prospective observational cohort study among patients admitted to the ICU for COVID-19-associated respiratory failure and their family members. Patients attended a one-year follow-up consultation with family members. Physical, functional and respiratory outcomes were collected. In addition, participants completed the Hospital Anxiety and Depression Scale and the Revised Impact of Event Scale. Qualitative components were collected during a 2-h face-to-face interview. Results: Fifty-four patients and 42 family members were included. Thirty-four (63%) patients reported chronic fatigue and 37 (68.5%) dyspnea. Computed tomography scans were abnormal in 34 patients (72.3%). Anxiety symptoms were present in 23 (48%) patients and 26 (66%) family members, depression in 11 (23%) and 13 (33%), and post-traumatic stress disorder in 12 (25%) and 23 (55%), respectively. Visit limitation was reported as the most painful experience for family members. Numerous patients recalled nightmares that contributed to the anxiety. Long-term reconstruction was difficult for both patients and family members. Conclusion: The vast majority of patients and their relatives reported long-term consequences on various physical and mental components, leading to a profound impact on their well-being.