Organ-on-a-Chip: Ubi sumus? Fundamentals and Design Aspects.

This review outlines the evolutionary journey from traditional two-dimensional (2D) cell culture to the revolutionary field of organ-on-a-chip technology. Organ-on-a-chip technology integrates microfluidic systems to mimic the complex physiological environments of human organs, surpassing the limitations of conventional 2D cultures. This evolution has opened new possibilities for understanding cell-cell interactions, cellular responses, drug screening, and disease modeling. However, the design and manufacture of microchips significantly influence their functionality, reliability, and applicability to different biomedical applications. Therefore, it is important to carefully consider design parameters, including the number of channels (single, double, or multi-channels), the channel shape, and the biological context. Simultaneously, the selection of appropriate materials compatible with the cells and fabrication methods optimize the chips' capabilities for specific applications, mitigating some disadvantages associated with these systems. Furthermore, the success of organ-on-a-chip platforms greatly depends on the careful selection and utilization of cell resources. Advances in stem cell technology and tissue engineering have contributed to the availability of diverse cell sources, facilitating the development of more accurate and reliable organ-on-a-chip models. In conclusion, a holistic perspective of in vitro cellular modeling is provided, highlighting the integration of microfluidic technology and meticulous chip design, which play a pivotal role in replicating organ-specific microenvironments. At the same time, the sensible use of cell resources ensures the fidelity and applicability of these innovative platforms in several biomedical applications.

Real-world assessment of Multipolar and Point-by-Point Mapping for Premature Ventricular Contraction Ablation.

PURPOSE: We aimed to assess acute and midterm efficacy of premature ventricular contraction (PVC) ablation guided by multielectrode and point-by-point (PbP) mapping. METHODS: Retrospective, international multicenter study of consecutive patients referred for PVC ablation in 10 hospital centers from January 2017 to December 2021. Based on the mapping approach two cohorts were identified: the "Multipolar group" where a dedicated high density mapping catheter was employed and the "PbP group" where mapping was performed with the ablation catheter. Procedural endpoints, safety, acute (procedural) and midterm efficacy were assessed. RESULTS: Of the 698 patients included in this study, 592 received activation mapping (46% males, median age of 55[41-65] years) - 248 patients in the Multipolar group and 344 patients in the PbP group. A higher number of activation points (432 [217-843] vs. 95 [42-185], p<0.001), reduced mapping time (40±38 min vs. 61±50 min, p<0.001), and shorter procedure time (124±60 min vs. 143±63 min, p<0.001) were reported in the Multipolar group. Both groups had high acute success rates (84.7% with Multipolar mapping vs. 81.3% with PbP mapping, p=0.63), as well as midterm efficacy (83.4% vs. 77.4%, p=0.08), with no significant differences in the risk of adverse events (6.0% vs. 3.5%, p=0.24). However, for left-sided PVC ablation specifically, there was higher midterm efficacy in the Multipolar group (80.7% vs. 69.5%, p=0.04), with multipolar mapping being an independent predictor of success (adjusted OR= 2.231 [95% CI, 1.476-5.108], p=0.02). CONCLUSIONS: Acute and midterm efficacy of PVC ablation is high with both multipolar and PbP mapping, although the former allow for quicker procedures and may potentially improve the outcomes of left-sided PVC ablation.

Available rehabilitation technology with the potential to be incorporated into the clinical practice of physiotherapists: A systematic review.

Background: The development of prototypes capable of intervening in the area of rehabilitation in physical therapy clinical practice activities that were previously carried out in a traditional way, that is, manually, demonstrates how technology is having an impact on professional careers such as physiotherapy. Objective: The purpose of this study is to present a comprehensive examination of various technologies employed in the facilitation of patient rehabilitation, with a focus on their potential integration within the clinical practice of physical therapists. Methods: We conducted a systematic search in four electronic databases (CINAHL, Embase, PEDro, and PubMed) for research on rehabilitation technologies. The eligible studies should demonstrate a clear utilization of technology in various aspects of the clinical approach to the rehabilitation process and have been published between 2000 and 2021 in either Portuguese or English. Results: A total of 18 articles that satisfied the selection criteria were included in the study. The studies were classified into four distinct categories of rehabilitation technologies, which were determined by the specific characteristics of the technology employed and its integration with the therapeutic approach to rehabilitation. These categories include digital technologies, artificial intelligence and/or robotics, virtual technologies, and hybrid technologies. Implications on Physiotherapy Practice: Rehabilitation technologies possess the capacity to effectively facilitate clinical activities performed by physical therapy professionals, including injury prevention, movement monitoring, and coordination of rehabilitation programs, with minimal or negligible intervention from the physical therapist. Further research is required to ascertain the precise capabilities of various technologies in collaborating with physiotherapists to deliver comprehensive care for patients' physical well-being, encompassing both therapeutic and preventive approaches. Trial Registration: PROSPERO registration number CRD42020222288.

An Unusual Coexistence: Right-Sided Colon Cancer and Intestinal Malrotation in an Adult.

Intestinal malrotation (IM), a rare congenital anomaly disrupting typical embryonic rotation around the superior mesenteric artery, is exceptionally uncommon in adults, with its link to colon cancer being even rarer. This article presents a case of colonic cancer in conjunction with IM in a 63-year-old male. Image studies and intraoperative findings show signs of IM. Open resection was performed due to concerns about vascular anomalies and abnormal lymphatic drainage. The case underscores the rarity of colon cancer in a malrotated gut, highlighting the necessity of preoperative identification for precise surgical planning and emphasizing the importance of careful dissection to prevent inadvertent vascular injury.

Bromelain as a natural anti-inflammatory drug: a systematic review.

Inflammation is a complex and necessary mechanism of an organ's response to biological, chemical and/or physical stimuli. In recent years, investigations on natural compounds with therapeutic actions for the treatment of different diseases have increased. Among these compounds, bromelain is highlighted, as a cysteine protease isolated from the Ananas comosus (pineapple) stem. This review aimed to evaluate the anti-inflammatory activity of bromelain, as well as its pathways on inflammatory mediators, through a systematic review with in vitro studies on different cell lines. The search was performed in PubMed, Science Direct, Scopus, Cochrane Library and Web of Science databases. Bromelain reduced IL-1ß, IL-6 and TNF-α secretion when immune cells were already stimulated in an overproduction condition by proinflammatory cytokines, generating a modulation in the inflammatory response through prostaglandins reduction and activation of a cascade reactions that trigger neutrophils and macrophages, in addition to accelerating the healing process.

A mathematical model for temporal cerebral blood flow response to acetazolamide evaluated in patients with Moyamoya disease.

BACKGROUND: Paired cerebral blood flow (CBF) measurement is usually acquired before and after vasoactive stimulus to estimate cerebrovascular reserve (CVR). However, CVR may be confounded because of variations in time-to-maximum CBF response (tmax) following acetazolamide injection. With a mathematical model, CVR can be calculated insensitive to variations in tmax, and a model offers the possibility to calculate additional model-derived parameters. A model that describes the temporal CBF response following a vasodilating acetazolamide injection is proposed and evaluated. METHODS: A bi-exponential model was adopted and fitted to four CBF measurements acquired using arterial spin labelling before and initialised at 5, 15 and 25 min after acetazolamide injection in a total of fifteen patients with Moyamoya disease. Curve fitting was performed using a non-linear least squares method with a priori constraints based on simulations. RESULTS: Goodness of fit (mean absolute error) varied between 0.30 and 0.62 ml·100 g-1·min-1. Model-derived CVR was significantly higher compared to static CVR measures. Maximum CBF increase occurred earlier in healthy- compared to diseased vascular regions. CONCLUSIONS: The proposed mathematical model offers the possibility to calculate CVR insensitive to variations in time to maximum CBF response which gives a more detailed characterisation of CVR compared to static CVR measures. Although the mathematical model adapts generally well to this dataset of patients with MMD it should be considered as experimental; hence, further studies in healthy populations and other patient cohorts are warranted.

Cotton plants overexpressing the Bacillus thuringiensis Cry23Aa and Cry37Aa binary-like toxins exhibit high resistance to the cotton boll weevil (Anthonomus grandis).

The cotton boll weevil (CBW, Anthonomus grandis) stands as one of the most significant threats to cotton crops (Gossypium hirsutum). Despite substantial efforts, the development of a commercially viable transgenic cotton event for effective open-field control of CBW has remained elusive. This study describes a detailed characterization of the insecticidal toxins Cry23Aa and Cry37Aa against CBW. Our findings reveal that CBW larvae fed on artificial diets supplemented exclusively with Cry23Aa decreased larval survival by roughly by 69%, while supplementation with Cry37Aa alone displayed no statistical difference compared to the control. However, the combined provision of both toxins in the artificial diet led to mortality rates approaching 100% among CBW larvae (LC50 equal to 0.26 PPM). Additionally, we engineered transgenic cotton plants by introducing cry23Aa and cry37Aa genes under control of the flower bud-specific pGhFS4 and pGhFS1 promoters, respectively. Seven transgenic cotton events expressing high levels of Cry23Aa and Cry37Aa toxins in flower buds were selected for greenhouse bioassays, and the mortality rate of CBW larvae feeding on their T0 and T1 generations ranged from 75% to 100%. Our in silico analyses unveiled that Cry23Aa displays all the hallmark characteristics of ß-pore-forming toxins (ß-PFTs) that bind to sugar moieties in glycoproteins. Intriguingly, we also discovered a distinctive zinc-binding site within Cry23Aa, which appears to be involved in protein-protein interactions. Finally, we discuss the major structural features of Cry23Aa that likely play a role in the toxin's mechanism of action. In view of the low LC50 for CBW larvae and the significant accumulation of these toxins in the flower buds of both T0 and T1 plants, we anticipate that through successive generations of these transgenic lines, cotton plants engineered to overexpress cry23Aa and cry37Aa hold promise for effectively managing CBW infestations in cotton crops.

Clinical course and disease burden of patients with generalized pustular psoriasis in Portugal: a multicenter retrospective cohort study.

OBJECTIVES: Generalized pustular psoriasis (GPP) is a rare, life-threatening skin inflammatory disorder. This study aimed to describe the disease course, treatment strategies, and healthcare utilization among patients with GPP in Portugal. METHODS: This multicentric, observational, retrospective study included consecutive adult patients with GPP undergoing a dermatology evaluation in different reporting institutions by experienced dermatologists between 2002 and 2023. RESULTS: A total of 59 patients were assessed. Most of the cohort had a previous history of plaque psoriasis (71%) and 83% presented at least one comorbidity. At the initial encounter, 64% of the cohort needed hospitalization. Systemic involvement was common, including fever (37%), and elevated white blood cell count and erythrocyte sedimentation rate/C-reactive protein (49%). Nearly, 73% of patients initiated systemic drugs, and 70% had to discontinue the first treatment. During the study, 98% of patients experienced at least one flare. At the last visit, 3.4% of patients had died, and 71.2% exhibited signs of active disease despite undergoing treatment. CONCLUSIONS: Our study demonstrates that GPP is a chronic, debilitating condition associated with systemic involvement, frequent flares, and hospitalizations, despite receiving multiple systemic treatments. Improved disease awareness and new treatments are needed to improve patient care and decrease the burden of the disease.

Preliminary hazard assessment of a new nature-inspired antifouling (NIAF) agent.

A recently synthesized aminated 3,4-dioxygenated xanthone (Xantifoul2) was found to have promising antifouling (AF) effects against the settlement of the macrofouler Mytilus galloprovincialis larvae. Preliminary assessment indicated that Xantifoul2 has reduced ecotoxicological impacts: e.g., being non-toxic to the marine crustacea Artemia salina (<10 % mortality at 50 µM) and showing low bioconcentration factor in marine organisms. In order to meet the EU Biocidal Product Regulation, a preliminary hazard assessment of this new nature-inspired antifouling (NIAF) agent was conducted in this work. Xantifoul2 did not affect the swimming ability of the planktonic crustacean Daphnia magna, the growth of the diatom Phaeodactylum tricornutum, and the cellular respiration of luminescent Gram-negative bacteria Vibrio fischeri, supporting the low toxicity towards several non-target marine species. Regarding human cytotoxicity, Xantifoul2 did not affect the cell viability of retinal human cells (hTERT-RPE-1) and lipidomic studies revealed depletion of lipids involved in cell death, membrane modeling, lipid storage, and oxidative stress only at a high concentration (10 µM). Accelerated degradation studies in water were conducted under simulated sunlight to allow the understanding of putative transformation products (TPs) that could be generated in the aquatic ecosystems. Both Xantifoul2 and photolytic-treated Xantifoul2 in the aqueous matrix were therefore evaluated on several nuclear receptors (NRs). The results of this preliminary hazard assessment of Xantifoul2, combined with the high degradation rates in water, provide strong evidence of the safety of this AF agent under the evaluated conditions, and provide the support for future validation studies before this compound can be introduced in the market.

Early Mobilization Decision after an Acute Ischemic Stroke: Protocol for an Umbrella Review.

INTRODUCTION: Stroke is considered one of the greatest public health challenges worldwide, with the ischemic subtype being the most prevalent. Various acute stroke clinical guidelines recommend early rehabilitation interventions, including very early mobilization. However, despite the studies conducted in recent years regarding when to initiate mobilization after an acute stroke, there are few systematic and personalized protocols based on the factors for which patient mobilization should ideally be performed. We aim to conduct an umbrella review of systematic reviews and meta-analyses to study the early mobilization decision after an acute ischemic stroke in comparison with conventional care and correlate the different approaches with patient clinical outcomes. METHODS AND ANALYSIS: We will perform a systematic search on PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Epistemonikos and Web of Science Core Collection databases. Retrieved studies will be independently reviewed by two authors and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias in the selected studies. We will use the 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist as the critical appraisal tool to assess cumulative evidence and risk of bias of the different studies. This will be the first umbrella review that compares early mobilization approaches in post-acute ischemic stroke. This study may help to define the optimal early mobilization strategy in stroke patients. PROSPERO registration number: CRD42023430494.

A Regulatory Perspective on Biosimilar Medicines.

By definition, biosimilar medicinal products are biological medicinal products that are similar to other biological medicinal products that are already on the market-the reference medicinal products. Access to biosimilar medicines is a current reality. However, to achieve this goal, it is extremely important to consistently and scientifically substantiate the regulatory requirements necessary for biosimilar medicines when accessing the market. Based on an analysis of the raw materials and the type of methods used in the manufacturing processes of biological medicines, it is known that this tends to be more complex for the quality of the finished product than the manufacture of molecules obtained through a chemical process. It is then relevant to highlight the main differences between both products: biological medicines manufactured using biotechnology and the current generics containing active pharmaceutical ingredients (APIs) obtained from synthetic processes. Once arriving at the approval process of these medicinal products, it is imperative to analyse the guidance documents and the regulatory framework that create the rules that allow these biosimilar medicinal products to come to the market. The present review aimed at documenting comparatively the specific provisions of European legislation, through the European Medicines Agency (EMA), as well as the legislation of the United States of America, through the Food and Drug Administration (FDA). This was then translated into a critical appraisal of what concerns the specific criteria that determine the favourable evaluation of a biosimilar when an application for marketing authorisation is submitted to different regulatory agencies. The gathered evidence suggests that the key to the success of biosimilar medicines lies in a more rigorous and universal regulation as well as a greater knowledge, acceptance, and awareness of health professionals to enable more patients to be treated with biological strategies at an earlier stage of the disease and with more affordable medicines, ensuring always the safety and efficacy of those medicines.

Dispersal history of SARS-CoV-2 in Galicia, Spain.

The dynamics of SARS-CoV-2 transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the USA became increasingly significant. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.

Routine Use of Neck Drains Following Thyroid Operations to Prevent Complications Is No Longer Advisable.

BACKGROUND: The use of cervical drains to prevent cervical hematoma or seroma after thyroidectomy remains a controversial issue. OBJECTIVE: Identify clinical and surgical risk factors for hematoma or seroma and evaluate the usefulness of routine use of drains following thyroid surgery. MATERIAL AND METHODS: The authors conducted a retrospective multicentric study related to consecutive patients submitted to thyroid surgery in seven Portuguese hospitals between January 2018 and December 2020 (n=945). The data collected included the following parameters: age and gender of the patients, anticoagulation or anti-aggregating therapy, histological diagnoses, type of surgery, the presence or absence of postoperative drains, thyroid weight, length of hospital stay, postoperative complications, and reinterventions. In this study, surgical complications evaluated were limited to the presence of hematoma or seroma. A total of 945 patients who underwent thyroid surgery were included in the study. Twenty-seven patients (2.9%, n=27) experienced complications classified as hematomas or seromas. In the series, significant differences were observed between the two groups according to hypocoagulation or anti-aggregation status (OR=3.62; 95% CI 1.14-11.4) (p=0.001) and the nature of histological diagnosis (toxic vs. non-toxic benign disease) (OR=6.59; 95% CI 1.83-23.7). Hypocoagulation or anti-aggregation status were independently associated with a higher risk of complications. The presence of drains was associated with longer hospitalization periods (p<0.001) and not a decreased need for reintervention. CONCLUSION: Cervical hematoma or seroma are rare complications associated with both hypocoagulation and anti-aggregation therapy and with the presence of benign toxic pathology. The use of drains does not decrease the need for reintervention and is even associated with a longer length of hospital stay; therefore, their routine use should not be advised.

High-Performance PEEK/MWCNT Nanocomposites: Combining Enhanced Electrical Conductivity and Nanotube Dispersion.

High-performance engineering thermoplastics offer lightweight and excellent mechanical performance in a wide temperature range. Their composites with carbon nanotubes are expected to enhance mechanical performance, while providing thermal and electrical conductivity. These are interesting attributes that may endow additional functionalities to the nanocomposites. The present work investigates the optimal conditions to prepare polyether ether ketone (PEEK)/multi-walled carbon nanotube (MWCNT) nanocomposites, minimizing the MWCNT agglomerate size while maximizing the nanocomposite electrical conductivity. The aim is to achieve PEEK/MWCNT nanocomposites that are suitable for melt-spinning of electrically conductive multifilament's. Nanocomposites were prepared with compositions ranging from 0.5 to 7 wt.% MWCNT, showing an electrical percolation threshold between 1 and 2 wt.% MWCNT (107-102 S/cm) and a rheological percolation in the same range (1 to 2 wt.% MWCNT), confirming the formation of an MWCNT network in the nanocomposite. Considering the large drop in electrical conductivity typically observed during melt-spinning and the drawing of filaments, the composition PEEK/5 wt.% MWCNT was selected for further investigation. The effect of the melt extrusion parameters, namely screw speed, temperature, and throughput, was studied by evaluating the morphology of MWCNT agglomerates, the nanocomposite rheology, and electrical properties. It was observed that the combination of the higher values of screw speed and temperature profile leads to the smaller number of MWCNT agglomerates with smaller size, albeit at a slightly lower electrical conductivity. Generally, all processing conditions tested yielded nanocomposites with electrical conductivity in the range of 0.50-0.85 S/cm. The nanocomposite processed at higher temperature and screw speed presented the lowest value of elastic modulus, perhaps owing to higher matrix degradation and lower connectivity between the agglomerates. From all the process parameters studied, the screw speed was identified to have the higher impact on nanocomposite properties.

Preserving visual acuity: a compelling 12-year case study of controlling neovascular age-related macular degeneration.

INTRODUCTION: In neovascular age-related macular degeneration (nAMD) trials, anti-VEGF injection frequency decreases after the first year, while outcomes remain primarily related to the number of injections. To the best of our knowledge, there are no reports of maintaining the best corrected visual acuity (BCVA) for more than 7 years in extension studies. OBJECTIVE: To report a 12-year follow-up of a real-world case of nAMD where BCVA was preserved from declining. CASE DESCRIPTION: A 67-year-old Caucasian female presented to our department in June 2010 due to decreased vision in her left eye (LE) within the preceding months. Examination showed a BCVA of 85 letters (L) in the right eye (RE) and 35 L in the LE. Fundus examination showed drusen in the macula of both eyes. Macular edema, loss of the macular lutein pigment, macular hypo/hyperpigmentation were observed in the LE. A diagnosis of Type 2 choroidal neovascular membrane (CNV) in the LE was established and within two months a Type 1 CNV developed in the RE. She undergone 9 injections of bevacizumab (six) and ranibizumab (three) within the first year of treatment in the LE and seven injections of ranibizumab within the first year in the RE. RESULTS: The LE had a mean of 5.2 injections per year, and the RE had a mean of 7.5 injections per year, from 2010 to 2022. RE's BCVA dropped by 8L (85L to 77L) and central retinal thickness (CRT) increased by 16 µm (276 µm to 292 µm) while LE's BCVA increased by 28L (35L to 63L) and CRT decreased by 369 µm (680 µm to 311 µm), at the twelfth year. CONCLUSIONS: Although the final visual outcome depends on baseline BCVA and lesion type or size, the number of injections is paramount in preserving BCVA and achieving favorable functional outcomes in nAMD, even after 12 years of treatment.

Developmental progression continues during embryonic diapause in the roe deer.

Embryonic diapause in mammals is a temporary developmental delay occurring at the blastocyst stage. In contrast to other diapausing species displaying a full arrest, the blastocyst of the European roe deer (Capreolus capreolus) proliferates continuously and displays considerable morphological changes in the inner cell mass. We hypothesised that developmental progression also continues during this period. Here we evaluate the mRNA abundance of developmental marker genes in embryos during diapause and elongation. Our results show that morphological rearrangements of the epiblast during diapause correlate with gene expression patterns and changes in cell polarity. Immunohistochemical staining further supports these findings. Primitive endoderm formation occurs during diapause in embryos composed of around 3,000 cells. Gastrulation coincides with elongation and thus takes place after embryo reactivation. The slow developmental progression makes the roe deer an interesting model for unravelling the link between proliferation and differentiation and requirements for embryo survival.

Serum and Vitreous Levels of Placenta Growth Factor in Diabetic Retinopathy Patients: Correlation With Disease Severity and Optical Coherence Tomographic Parameters.

Purpose The primary objective of this study was to compare placenta growth factor (PlGF) levels in the serum and vitreous of diabetic retinopathy (DR) patients to non-diabetic controls. Additionally, the study aimed to establish associations between serum and vitreous PlGF concentrations and to examine the correlation between vitreous PlGF in DR patients and morphological parameters. Methods This study included serum and vitreous samples from 38 patients, including 21 patients with DR and 17 non-diabetic controls. The control group included non-diabetic patients with rhegmatogenous retinal detachment with retinal tears secondary to posterior vitreous detachment or trauma. PlGF levels were quantified in vitreous and serum samples using an enzyme-linked immunosorbent assay (ELISA). Optical coherence tomography (OCT) scans from DR patients were evaluated to measure the central retinal thickness (CRT) and macular volume (MV). Results DR patients had significantly higher mean vitreous PlGF levels compared to non-DR patients (70.0±39.2 vs. 46.47±9.7 pg/mL, p-value=0.004). However, no significant increase in mean serum PlGF levels was observed in DR patients (p-value=0.232). Within the DR group, proliferative DR (PDR) patients presented significantly higher vitreous PlGF levels than non-PDR (NPDR) patients (76.5±41.0 vs. 42.5±5.0 pg/mL, p-value=0.009). There was no association between serum and vitreous PlGF levels. The correlation between vitreous PlGF levels and morphological parameters was rsp=0.175, p-value=0.488 for CRT, and rsp=0.288, p-value=0.262 for MV. Conclusion This study emphasizes the important role of PlGF in neovascularization, specifically highlighting its overexpression exclusively in vitreous from PDR patients. The observed increase in PlGF levels may be indicative of disease severity. The lack of correlation between vitreous and serum PlGF levels suggests a potential dissociation between intravitreal and systemic PlGF synthesis. Consequently, targeting PlGF in therapeutic approaches may offer an additional strategy for ocular pathologies with a neovascular component.

Application of nanoformulations as a strategy to optimize chemotherapeutic treatment of glioblastoma: a systematic review.

The aim of this review was to explore the advances of nanoformulations as a strategy to optimize glioblastoma treatment, specifically focusing on targeting and controlling drug delivery systems to the tumor. This review followed the PRISMA recommendations. The studies were selected through a literature search conducted in the electronic databases PubMed Central, Science Direct, Scopus and Web of Science, in April 2023, using the equation descriptors: (nanocapsule OR nanoformulation) AND (glioblastoma). Forty-seven investigations included were published between 2011 and 2023 to assess the application of different nanoformulations to optimize delivery of chemotherapies including temozolomide, carmustine, vincristine or cisplatin previously employed in brain tumor therapy, as well as investigating another 10 drugs. Data demonstrated the possible application of different matrices employed as nanocarriers and utilization of functionalizing agents to improve internalization of chemotherapeutics. Functionalization was developed with the application of peptides, micronutrients/vitamins, antibodies and siRNAs. Finally, this review demonstrated the practical and clinical application of nanocarriers to deliver multiple drugs in glioblastoma models. These nanomodels might ideally be developed using functionalizing ligand agents that preferably act synergistically with the drug these agents carry. The findings showed promising results, making nanoformulations one of the best prospects for innovation and improvement of glioblastoma treatment.

Understanding Ocular Surface Disease in Glaucoma: A Comparative Analysis of Symptoms and Objective Parameters.

Background Glaucoma is a progressive optic neuropathy that may result in irreversible visual impairment and can diminish quality of life. Lowering intraocular pressure (IOP) through topical eyedrops is usually the primary approach to managing glaucoma. However, long-term treatment poses a risk to ocular surface health, leading to ocular surface disease (OSD). Preservative-containing eyedrops are implicated in OSD development due to their detrimental effects on the tear film and goblet cell density. OSD symptoms may impact patient compliance due to local side effects. This study aims to assess OSD in glaucoma patients receiving topical treatment, quantify symptoms and objective ocular surface parameters, and compare them to a control group not using topical glaucoma medications. Methodology Patients diagnosed with primary open-angle glaucoma receiving topical treatment and a control group were included in this study. To assess OSD, patients completed the Ocular Surface Disease Index (OSDI) questionnaire to evaluate symptoms and underwent objective measurements of ocular surface parameters using a keratograph. These parameters included assessments of bulbar redness and non-invasive keratograph tear break-up time (NIKTBUT). Results A cohort of 92 patients was subjected to examination, comprising 66 individuals diagnosed with glaucoma and 26 controls. Within the glaucoma patient subset, the mean number of IOP-lowering drugs administered was 2.42 ± 0.18, with 22.7% exclusively utilizing preservative-free eye drops. Our investigations unveiled a substantial prevalence of OSD symptoms, manifesting not only within the glaucoma cohort but also among the control group, with 72.7% and 53.8%, respectively (p = 0.224), reporting moderate-to-severe symptoms (OSDI > 23). Remarkably, OSDI scores exhibited higher values among female participants (p = 0.039) and glaucoma patients using prostaglandins (p<0.001) and were negatively correlated to the number of IOP-lowering drugs used (-0.448; p < 0.001). Furthermore, employing keratograph assessment, we discerned heightened bulbar redness (1.86 ± 0.07) in the glaucoma group compared to the control group (1.58 ± 0.07; p = 0.008). Glaucoma subgroup analyses further unveiled higher bulbar redness among glaucoma patients employing carbonic anhydrase inhibitors (p = 0.035) and applying medication preservatives (p = 0.045) but lower among individuals using beta-blockers (p = 0.018). However, the NIKTBUT did not show significant variance between the two groups (glaucoma group: 10.19 ± 0.85 seconds; control group: 10.96 ± 1.37 seconds; p = 0.499). Conclusions Our study revealed a significant prevalence of OSD in our sample, with the OSDI questionnaire showing limited specificity. The notable increase in bulbar redness pointed to an elevated prevalence of OSD among glaucoma patients, emphasizing the considerable impact of preservatives on ocular surface damage. Recognizing the potential damage to the tear film and ocular surface is crucial for glaucoma experts, who must employ comprehensive therapeutic strategies to mitigate symptoms, advocating for the preferential use of preservative-free medications, when possible, for optimizing long-term treatment.