HTK solution cardioplegia in paediatric patients: a meta-analysis.

INTRODUCTION: Cardioplegia, a therapy designed to induce reversible cardiac arrest, revolutionised cardiovascular surgery. Among the various pharmacological approaches is the histidine-tryptophan-ketoglutarate (HTK) solution. Despite numerous studies, no meta-analysis has investigated the efficacy of the HTK solution in the paediatric population. Therefore, we aim to conduct a meta-analysis comparing HTK and other cardioplegia solutions in paediatric patients undergoing cardiovascular surgery. METHODS: PubMed, Embase and Cochrane databases were searched from inception through April 2024. Endpoints were computed in odds ratios (OR) with 95% Confidence Intervals (CI) for dichotomous variables, whereas continuous variables were compared using mean differences (MD) with 95% CI. RESULTS: 11 studies comprising 1,349 patients were included, of whom 677 (50.19%) received HTK cardioplegia. The results were similar between groups regarding mortality (OR 0.98; 95% CI 0.29, 3.29), length of hospital (MD 0.32 days; 95% CI -0.88, 1.51), MV (MD -17.72 hours; 95% IC -51.29, 15.85), arrhythmias (OR 1.27; 95% CI 0.83, 1.95;) and delayed sternal closure (OR 0.89; 95% 0.56, 1.43). However, transfusion volume was lower in the HTK group (MD -452.39; 95% CI -890.24, -14.53; p=0.04). CONCLUSION: The use of HTK solution was demonstrated to be similar regarding its clinical efficacy to other approaches for cardioplegia, and it may present advantages to patients prone to hypervolemia.

Complex shape markers can detect alterations in the spatial distribution of cell nuclei in human lung squamous cell carcinoma: a useful tool for automatic analysis?

Lung cancer is the leading cause of cancer-related death. The use of computational methods to quantify changes that are not perceptible to the human eye is increasing in digital pathology imaging and has quickly improved detection rates at a low cost. Therefore, the present study aims to use complex computational shape markers as tools for automated analysis of the spatial distribution of cells in microscopy images of squamous cell lung carcinoma (SqCC). Photomicrographs from pathology glass slides in the LC25000 dataset were used in this study. Compared with those of the control, the fractal dimension (28%) and lacunarity (41%) of the cell nuclei changed in SqCC. The multifractal analysis revealed a significant difference in parameters Dq, α, and f(α) for all values of q (-10 to + 10), with a greater increase for more positive q values. The values at q + 10 increased by 34% for Dq, 36% for α, and 53% for f(α) in the SqCC images. The circularity, area, and perimeter also changed in the SqCC images. However, the parameters of aspect ratio, roundness, and solidity did not significantly differ between SqCC and benign tissue. The complex shape markers with the greatest changes in this study were the f(α) values for multifractality (53%) and lacunarity (41%). In conclusion, automated quantification of the spatial distribution of cell nuclei can be a fast, low-cost tool for evaluating the microscopic characteristics of SqCC; therefore, complex shape markers could be useful tools for software and artificial intelligence to detect lung carcinoma.

Human papillomavirus infection affects the immune microenvironment and antigen presentation in penile cancer.

Penile squamous cell carcinoma (PSCC) is a largely neglected condition, predominantly affecting underdeveloped regions, and is associated with risk factors such as low socioeconomic status, phimosis, and human papillomavirus (HPV) infection. Unlike other urogenital cancers, its pathophysiology and therapeutic targets remain poorly understood, particularly regarding the immune response to the tumor microenvironment. This study aims to investigate immune cell infiltration profiles, dendritic cell maturation, and lymphocyte apoptosis in both HPV-positive and HPV-negative PSCC. Clinical and histopathological data, along with peripheral blood and tumor tissue samples, were collected from 30 patients (66.6% were HPV-positive and 33.3% HPV-negative), with an additional 19 healthy donors serving as controls. Tumor-infiltrating immune cells were analyzed following enzymatic digestion of tumor tissue, enabling detailed phenotypic characterization. A simulated tumor microenvironment was created using supernatants derived from primary cultures of HPV-positive PSCC tumors. Peripheral blood mononuclear cells were isolated and differentiated into dendritic cells (Mo-DCs) for further phenotyping and lymphoproliferation assays. Lymphocytes from healthy donors and patients were exposed to tumor culture supernatants to evaluate apoptosis induced by the tumor microenvironment. Results showed that HPV-positive tumors exhibited lower T lymphocyte frequencies compared to HPV-negative tumors. Additionally, patients infected with high-risk HPV demonstrated reduced maturation rates of Mo-DCs and decreased expression of co-stimulatory molecules on these cells compared to healthy donors. Furthermore, Mo-DCs from hrHPV-positive patients showed impaired lymphoproliferation capacity relative to controls, while HPV-negative patients exhibited a trend towards reduced lymphoproliferative ability. Regarding the simulated tumor microenvironment, lymphocytes from healthy donors underwent apoptosis, contrasting with patients' lymphocytes, which showed increased viability when cultured with tumor supernatants. These results underscore the impact of HPV infection on T lymphocyte infiltration, Mo-DC maturation, and lymphocyte survival in PSCC, offering critical insights for advancing our understanding of the tumor microenvironment and guiding the development of immunotherapy strategies.

The impact of particle size of nanostructured lipid carriers on follicular drug delivery: A comprehensive analysis of mouse and human hair follicle penetration.

Introduction: Follicular delivery is one of the targeted drug delivery methods aiming to target the hair follicles. The accumulation and retention time of targeted drugs is enhanced when nanoparticles are used as drug carriers. Particle size is one of the important factors affecting the penetration and accumulation of particles in the hair follicles, and there is a controversy in different studies for the best particle size for follicular delivery. Mouse models are mostly used in clinical trials for dermal, transdermal, and follicular delivery studies. Also, it is essential to investigate the reliability of the results between human studies and mouse models. Methods: Curcumin-loaded nanostructured lipid carriers (NLCs), as a fluorescent agent, with three different particle size ranges were prepared using the hot homogenization method and applied topically on the mouse and human study groups. Biopsies were taken from applied areas on different days after using the formulation. The histopathology studies were done on the skin biopsies of both groups using confocal laser scanning microscopy (CLSM). We compared the confocal laser scanning microscope pictures of different groups, in terms of penetration and retention time of nanoparticles in human and mouse hair follicles. Results: The best particle size in both models was the 400 nm group but the penetration and accumulation of particles in human and mouse hair follicles were totally different even for the 400 nm group. In human studies, 400 nm particles showed good accumulation after seven days; this result can help to increase the formulation using intervals. Conclusion: The best particle size for human and mouse follicular drug delivery is around 400 nm and although mouse models are not completely suitable for follicular delivery studies, they can be used in some conditions as experimental models.

Decoding mutational hotspots in human disease through the gene modules governing thymic regulatory T cells.

Computational strategies to extract meaningful biological information from multiomics data are in great demand for effective clinical use, particularly in complex immune-mediated disorders. Regulatory T cells (Tregs) are essential for immune homeostasis and self-tolerance, controlling inflammatory and autoimmune processes in many diseases with a multigenic basis. Here, we quantify the Transcription Factor (TF) differential occupancy landscape to uncover the Gene Regulatory Modules governing lineage-committed Tregs in the human thymus, and show that it can be used as a tool to prioritise variants in complex diseases. We combined RNA-seq and ATAC-seq and generated a matrix of differential TF binding to genes differentially expressed in Tregs, in contrast to their counterpart conventional CD4 single-positive thymocytes. The gene loci of both established and novel genetic interactions uncovered by the Gene Regulatory Modules were significantly enriched in rare variants carried by patients with common variable immunodeficiency, here used as a model of polygenic-based disease with severe inflammatory and autoimmune manifestations. The Gene Regulatory Modules controlling the Treg signature can, therefore, be a valuable resource for variant classification, and to uncover new therapeutic targets. Overall, our strategy can also be applied in other biological processes of interest to decipher mutational hotspots in individual genomes.

Correction: Santos et al. Early Peri-Implant Bone Healing on Laser-Modified Surfaces with and without Hydroxyapatite Coating: An In Vivo Study. Biology 2024, 13, 533.

There were two errors in the original publication [...].

The Development of a Flexible Humidity Sensor Using MWCNT/PVA Thin Films.

The exponential demand for real-time monitoring applications has altered the course of sensor development, from sensor electronics miniaturization, e.g., resorting to printing techniques, to low-cost, flexible and functional wearable materials. Humidity sensing has been used in the prevention and diagnosis of medical conditions, as well as in the assessment of physical comfort. This paper presents a resistive flexible humidity sensor composed of silver interdigitated electrodes (IDTs) screen printed onto polyimide film and an active layer of multiwall carbon nanotubes (MWCNT) dispersed in a water-soluble polymer, polyvinyl alcohol (PVA). Different MWCNT/PVA sensor sizes and MWCNT percentages are tested to study their effect on the initial electrical resistance (Ri) values and sensor response at different humidity percentages. The results show that the Ri values decrease with the increase in % MWCNT. The sensor size did not influence the sensor response, while the % MWCNT affected the sensor behavior upon relative humidity (RH) increments. The 1% MWCNT/PVA sensor showed the best response, reaching a relative electrical resistance, ΔR/R0, of 509% at 99% RH. Comparable with other reported sensors, the produced MWCNT/PVA flexible sensor is simpler, greener and shows a good sensitivity to humidity, being easily incorporated in wearable monitoring applications, from sports to medical fields.

Intraretinal Microvascular Abnormalities in Eyes with Advanced Stages of Nonproliferative Diabetic Retinopathy: Comparison Between UWF-FFA, CFP, and OCTA-The RICHARD Study.

INTRODUCTION: This study aimed to evaluate intraretinal microvascular abnormalities (IRMA) in eyes with advanced nonproliferative diabetic retinopathy (NPDR) using multimodal approach in co-located areas focusing on central retina (up to 50°) and to look at possible correlations between IRMA and other structural changes, like ischemia and presence of microaneurysms. METHODS: The RICHARD study (NCT05112445) included 60 eyes from 60 patients with type 2 diabetes with moderate-severe NPDR, diabetic retinopathy severity levels 43, 47, and 53 (DRSS). IRMA were defined as capillary tortuosity covering a minimum circular area of 300 µm (calculated to correspond to the Early Treatment Diabetic Retinopathy Study standard photo 8A) and were identified using multimodal imaging with distinct fields of view (FoV): color fundus photography (CFP) using a Topcon TRC-50DX camera (Topcon Medical Systems, Japan), Optos California ultra wide field fundus fluorescein angiography (UWF-FFA) (Optos plc, UK), and swept-source optical coherence tomography angiography (SS-OCTA) (PLEX® Elite 9000, ZEISS, USA). Different areas of the retina were examined: central macula (up to 20°) and posterior pole (between 20° and 50°). RESULTS: Multimodal imaging was used to identify IRMA in co-located areas (FoV < 50°) including UWF-FFA, CFP, and SS-OCTA. In eyes with DRSS levels 47 and 53, IRMA were identified in both areas of the retina, while in eyes with DRSS level 43, IRMA were detected only outside of the central macula (FoV > 20°). Our results show that when evaluating the presence of IRMA (FoV < 50°), UWF-FFA detected 203 IRMA, SS-OCTA detected 133 IRMA, and CFP detected 104 IRMA. Our results also show that the presence of IRMA was positively associated with presence of microaneurysms. CONCLUSIONS: Identification of IRMA in eyes with advanced NPDR is better achieved by UWF-FFA than CFP and SS-OCTA. A statistically significant correlation was found between the presence of IRMA and the increase in number of microaneurysms. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05112445.

Paediatric Emergency Nurses' Perception of Medication Errors: A Qualitative Study.

Patient safety is fundamental to healthcare. Adverse events, particularly medication errors, cause harm to patients, especially the paediatric population in the emergency department. AIM: To explore paediatric emergency nurses' perceptions of medication administration errors. METHOD: A qualitative, ethnomethodological, descriptive study. The participants were nurses working in the paediatric emergency department. Data were collected through in-depth individual interviews with paediatric emergency nurses. The study excluded nurses employed for less than six months. Ten individual interviews were carried out. All interviews were face-to-face and audio-recorded with the participant's consent. Interviews took between 52 min and 1 h 25 min. A questions guide was followed during the interviews. The analysis of the data was carried out according to the scheme proposed by Taylor and Bogdan. RESULTS: The participants' discourse revealed three main categories: Safety culture, transmitted by supervisors and safety groups. Teamwork, with good communication and a positive relationship. Error management, the lack of formal support and negative feelings despite an understanding of the multifactorial nature of errors. The study identifies several challenges in the healthcare system. Emphasis was placed on the perception of errors in terms of patient harm, while near misses or dose delays or omissions are not treated as errors. CONCLUSIONS: Although institutions have implemented safety culture strategies, nurses have not fully embraced them. There is a need to promote a positive safety culture and a safe working environment that encourages communication within the team. The hospital should provide training in safe management and patient safety and develop effective protocols. This study was not registered.

Mentha aquatica (Water Mint) as a Source of Active Pharmaceutical and Cosmetic Ingredients: A Critical Review.

Mentha aquatica L., or water mint, is an important member of the Mentha genus, and has long been used in traditional medicine, mainly to treat respiratory diseases such as the common cold. Nevertheless, although over the years many studies have shown that it's potential grows beyond this use, a review that highlights M. aquatica L.'s true potential is still lacking. Thus, the main purpose of the present article is to provide a thorough and multidisciplinary critical review of M. aquatica L., including its phytochemical characterization, main bioactivities, and current marketed cosmetic products. Many compounds have been identified as part of M. aquatica L. composition, such as terpenes, phenolic acids, phenols, and terpenoids, which have been linked to a vast therapeutic potential, namely anti-inflammatory, antioxidant, antibacterial, antifungal, antiobesity, and hepatoprotection bioactivities, with additional anticancer potential for several types of tumors (breast, lung, and skin), and psycho and neuroactive potential in depression, or Alzheimer's or Parkinson's disease. Additionally, it has been proven to be suitable for cosmetic application since several cleansing, hydrating, protecting, and/or odor masking products containing it are already available, with the main functions attributed to M. aquatica including refreshing/cooling effects, calming/soothing/relaxing effects, and purifying effects, properties closely related to its anti-inflammatory and antioxidant bioactivities. Hence, M. aquatica is an extremely versatile plant, with its extracts and essential oils having great therapeutic and cosmetic potential. With many marketed cosmetic products, future studies should focus on this plant's medicinal aspects, so that 1 day it can be part of therapeutic regimens.

Retinopathy of Prematurity in Eight Portuguese Neonatal Intensive Care Units: Incidence, Risk Factors, and Progression-A Prospective Multicenter Study.

BACKGROUND/OBJECTIVES: Retinopathy of prematurity (ROP) is a retinal neovascular disease affecting preterm infants. Identifying risk factors for its development and progression is critical for effective screening and prevention. This study aimed to analyze the incidence of ROP and identify key risk factors for its development and progression. METHODS: We conducted a prospective, observational cohort study on 455 neonates (gestational age [GA] < 32 weeks or birth weight < 1500 g) across eight Portuguese NICUs. RESULTS: ROP incidence was 37.8%, with 4.6% requiring treatment. Multivariate analysis identified low GA and the number of red blood cell (RBC) transfusions as significant factors for ROP development and progression. After adjusting for these variables, platelet transfusions, high maximum fraction of inspired oxygen (FiO2) in the second week, and surfactant use remained significantly associated with ROP development, while early and late sepsis, maternal chronic hypertension, and delayed enteral nutrition were associated with progression to ROP requiring treatment. CONCLUSIONS: These findings underscore the importance of addressing low GAs and adult RBC transfusions in ROP risk management and suggest that maximum FiO2, platelet transfusions, and sepsis also play crucial roles. Larger studies are needed to validate these results and explore preventive interventions, particularly regarding the impact of multiple adult RBC transfusions on fetal hemoglobin percentages.

Severity Profile of COVID-19 in Hospitalized Pediatric Patients.

OBJECTIVE: We aimed to describe the clinical characteristics associated with severity in children hospitalized with COVID-19. METHOD: This was an epidemiological cohort study conducted in two hospitals, one of which was a reference center for the treatment of COVID-19 cases. Data were collected from the reports generated by the hospital epidemiology centers and the medical records of patients aged between 0 and 14 years with a diagnosis of COVID-19, hospitalized between March 2020 and June 2021. To analyze the association between the clinical profile and severity, the cases were classified as severe (severe and critical) and non-severe (asymptomatic, mild, and moderate). RESULTS: Of the 191 children followed up in the cohort, 73.3% developed the severe form. The percentage of children with oxygen saturation below 95% was 46.6%. In the multivariate analysis, a higher risk of severity was estimated among children with uncontrolled asthma (RR = 13.2), who were overweight or obese (RR = 3.21), who had cough symptoms (RR = 2.72), and those aged under one year (RR = 3.23). CONCLUSIONS: This result underscores the need to improve healthcare at every level for children and for the management of asthma and nutrition when considering children with this clinical profile who are diagnosed with COVID-19.

The Impact of TBXA2R Gene Variants on the Risk of Aspirin-Induced Upper Gastrointestinal Bleeding: A Case-Control Study.

Objective: Upper gastrointestinal bleeding (UGIB) has been identified as a potential adverse drug reaction associated with the use of low-dose aspirin (LDA). This study aimed to investigate the relationship between variants in the TBXA2R gene, which is involved in platelet aggregation, and the risk of UGIB in patients with cardiovascular diseases treated with LDA. Methods: A case-control study was conducted at a Brazilian hospital complex. Three groups were defined: (1) case group (n = 50): patients with cardiovascular disease who used LDA and were diagnosed with UGIB of non-variceal etiology, (2) LDA control group (n = 50): patients with cardiovascular disease who used LDA without developing UGIB, and (3) healthy control group (n = 189). Data were collected through face-to-face interviews, and blood samples were collected for the analysis of Helicobacter pylori infection and genotyping of 3 genetic variants [rs2238631 (C > T), rs4807491 (A > G), and rs1131882 (A > G)]. Results: The case group had a significantly higher frequency of carriers of the rs4807491.G allele compared to the control group of LDA users (P-value = .004). No significant difference was observed in the proportion of carriers of the rs2238631.T and 1131882.G variants between the studied groups. Carriers of rs2238631.T (OR: 4.515, 95% CI: 1.37-14.89) and rs4807491.G allele (OR: 3.232, 95% CI: 1.12-9.37) exhibited a higher risk of UGIB. Conclusion: These findings suggest that the presence of the rs2238631 and rs4807491 variant alleles is associates with a 3- to 4-fold increased risk of UGIB in patients with cardiovascular diseases treated with LDA. Future studies with larger sample sizes should confirm these results and to better identify individuals who may benefit from chronic LDA use.

Living the first years in a pandemic: children's linguistic development and related factors in and out of the COVID-19 lockdowns.

This retrospective study provides insights on linguistic development in exceptional circumstances assessing 378 children (between 2;6 and 3;6) who lived their first years during the COVID-19 pandemic and comparing it with normative data collected before this period (CDI-III-PT; Cadime et al., 2021). It investigates the extent to which linguistic development was modulated by a complex set of factors, including sex, maternal education, book reading, language-promoting practices, COVID-19 infection, parental stress and sleeping problems, considering three periods (during lockdowns, out of lockdowns and at present). The results show a substantial negative effect of the pandemic on both lexical and syntactic development. Considering individual variation, structural equation modelling unveiled a complex scenario in which age, sex, book reading, language-promoting practices, sleeping problems and COVID-19 infection showed a direct effect on linguistic development. Maternal education and parental stress had an indirect effect on children's language, mediated by book reading and sleeping problems, respectively.

Water deprivation induces a systemic pro-catabolic state that differentially affects oxidative and glycolytic skeletal muscles in male mice.

Dehydration, characterized by the loss of total body water and/or electrolytes due to diseases or inadequate fluid intake, is prevalent globally but often underestimated. Its contribution to long-term chronic diseases and sarcopenia is recognized, yet the mechanisms involved in systemic and muscle protein metabolism during dehydration remain unclear. This study investigated metabolic adaptations in a 36-hour water deprivation (WD) model of mice. Male C57BL/6 mice underwent 36-h WD or pair-feeding at rest, with assessments of motor skills along with biochemical, and metabolic parameters. Dehydration was confirmed by hypernatremia, body mass loss, hyporexia, and increased activity of vasopressinergic and oxytocinergic neurons compared to controls. These results were associated with liver mass loss, decreased glycaemia, and increased cholesterolemia. Additionally, increased VO2 and a decreased respiratory exchange ratio indicated reduced carbohydrate consumption and potentially increased protein use during dehydration. Thus, skeletal muscle protein metabolism was evaluated due to its high protein content. In the oxidative muscles of the WD group, total and proteasomal proteolysis increased, which was associated with decreased Akt-mediated intracellular signaling. Interestingly, there was an increase in fiber cross-sectional area, likely due to higher muscle water content caused by increased intracellular osmolality induced by protein catabolism products. Conversely, no changes were observed in protein turnover or water content in glycolytic muscles. These findings suggest that short-term WD imposes a pro-catabolic state, depleting protein content in skeletal muscle. However, skeletal muscle may respond differently to dehydration based on its phenotype and might adapt for a limited time.

Immunosuppressants in women with repeated implantation failure in assisted reproductive techniques: a systematic review and meta-analysis.

Objective: To compare outcomes in patients with repeated implantation failure undergoing Intracytoplasmic Sperm Injection/In vitro fertilization (IVF/ICSI) plus immunosuppressants such as prednisolone, prednisone, or cyclosporine A versus the use of IVF/ICSI alone. Data source: Databases were systematically searched in PubMed, Cochrane, and Embase databases in September 2023. Study Selection: Randomized clinical trials and observational studies with the outcomes of interest were included. Data collect: We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics. Data were analyzed using Review Manager 5.4.The main outcomes were live birth, miscarriage, implantation rate, clinical pregnancy, and biochemical pregnancy. Data synthesis: Seven studies with 2,829 patients were included. Immunosuppressive treatments were used in 1,312 (46.37%). Cyclosporine A improved implantation rate (OR 1.48; 95% CI 1.01-2.18) and clinical pregnancy (1.89, 95% CI 1.14-3.14). Compared to non-immunosuppressive treatment, prednisolone and prednisone did not improve live birth (OR 1.13, 95% CI 0.88-1.46) and miscarriage (OR 1.49, 95% CI 1.07-2.09). Prednisolone showed no significant effect in patients undergoing IVF/ICSI, clinical pregnancy (OR 1.34; 95% CI 0.76-2.36), or implantation rate (OR 1.36; 95% CI 0.76-2.42). Conclusion: Cyclosporine A may promote implantation and clinical pregnancy rates. However, given the limited sample size, it is important to approach these findings with caution. Our results indicate that prednisolone and prednisone do not have any beneficial effects on clinical outcomes of IVF/ICSI patients with repeated implantation failure. PROSPERO: CRD42023449655.

Challenges and limitations in meta-analyses of complications in neurosurgery: Systematic review with proposed approach and checklist to mitigate errors and improve the assessment of the real-world experience.

Meta-analyses are highly valued in medical science, yet accurately reporting complications in neurosurgical studies remains challenging. Examples include inconsistencies in defining and classifying complications and variations in reporting methods. This lack of reproducibility and comparability, along with other issues related to biases, hinders the ability of meta-analyses to yield significant advancements. This systematic review investigated the challenges and limitations inherent in meta-analyses of complications in neurosurgery. Based on the identified challenges and our group's experience, we developed a practical checklist to mitigate and avoid common errors in meta-analyses of complications in neurosurgery.We searched PubMed, Embase, and Web of Science for studies addressing challenges in assessing complications in neurosurgery. The main findings were qualitatively synthesized to identify common challenges and limitations. The proposed checklist was developed using a modified Delphi technique. Eleven studies were included, uncovering heterogeneity and a lack of standardization regarding the classification of complications in neurosurgery across various authors and institutions. They suggested solutions such as implementing a more uniform classification system. Additionally, the NeuroComp Meta-Analysis Checklist was developed, comprising 23 items divided into 5 domains, with a practical approach and suggestions on how to deal with the challenges when meta-analyzing.We identified numerous challenges and concerns when assessing complications in the neurosurgical field. The NeuroComp Meta-Analysis Checklist incorporated methodologies and approaches we utilized in several previously published meta-analyses. While we acknowledge that the proposal cannot solve all the issues involved in comparing and meta-analyzing complications in neurosurgery, it has the potential to enhance the informativeness of future meta-analyses and help authors mitigate common errors. Ultimately, this tool has the potential to contribute to the advancement of accumulating real-world evidence in neurosurgical science.