Recent publications
Introduction
Venous thromboembolism is the third most frequent acute cardiovascular pathology in the general population. Several risk factors have been described, including pregnancy and postpartum status.
Case Presentation
We present the case of a puerperal woman (after the fifth natural childbirth), who was diagnosed with grade II gestational hypertension four weeks before giving birth, when bed rest was recommended by her physician. The patient was admitted for dyspnea and extreme fatigue during minimal exertion, with symptoms starting immediately after birth and suddenly aggravated three days prior to presentation. She had a heart rate of 115 bpm and a blood pressure of 140/90 mmHg. The resting electrocardiogram depicted sinus tachycardia, signs of right ventricular strain and S1Q3T3 pattern. The echocardiography revealed a severely enlarged right ventricle with poor systolic function, as well as signs of right ventricle pressure overload and a high probability of pulmonary hypertension. NT-proBNP and high-sensitive troponin were mildly elevated. The computed tomographic pulmonary angiography confirmed the diagnosis of intermediate-high risk pulmonary embolism. Under treatment with unfractionated heparin, the patient’s condition did not improve. After a thorough, team-based evaluation of the risk/benefit ratio, standard catheter-directed thrombolysis was performed, with good immediate and long-term outcomes.
Conclusion
Catheter directed thrombolysis could be an effective treatment of postpartum pulmonary thromboembolism, with a reasonable hemorrhagic risk. Postpartum and pregnant women are usually excluded from clinical trials, thus disproportionately limiting their access to novel therapies with high potential benefits. In such patients, an informed, individualized, team-based decision should be made.
Objective
Heterozygous germline loss-of-function variants in AIP are associated with young-onset growth hormone and/or prolactin-secreting pituitary tumours. However, the pathogenic role of the c.911G>A; p.(Arg304Gln) (R304Q) AIP variant has been controversial. Recent data from public exome/genome databases show this variant is not infrequent. The objective of this work was to reassess the pathogenicity of R304Q based on clinical, genomic and functional assay data.
Design, materials and methods
Data were collected on published R304Q pituitary neuroendocrine tumour cases, and from International Familial Isolated Pituitary Adenoma Consortium R304Q cases (n=38, R304Q cohort). Clinical features, population cohort frequency, computational analyses, prediction models, presence of loss-of-heterozygosity and in vitro/in vivo functional studies were assessed and compared to data from pathogenic/likely pathogenic AIP variant patients (AIPmut cohort, n=184).
Results
Of 38 R304Q patients, 61% (23/38) had growth hormone excess, in contrast to 80% of AIPmut cohort (147/184, p<0.001). R304Q cohort was older at disease onset and diagnosis than the AIPmut cohort (median (quartiles) onset: 25y (16-35) vs 16y (14-23), p<0.001; median (quartiles) diagnosis: 36y (24-44) vs 21y (15-29), p<0.001). R304Q is present in gnomADv2.1 (0.31%) and UK Biobank (0.16%), including three persons with homozygous R304Q. No loss-of-heterozygosity was detected in four R304Q pituitary neuroendocrine tumour samples. In silico predictions and experimental data were conflicting.
Conclusions
Evidence suggests that R304Q is not pathogenic for pituitary neuroendocrine tumour. We recommend changing this variant classification to likely benign, and do not recommend pre-symptomatic genetic testing of family members or follow up of already identified unaffected individuals with the R304Q variant.
The growing consumption of processed foods, including meat-based and plant-based burgers (PBM), raises concerns about their long-term health effects. While PBM burgers are marketed as healthier alternatives, their biochemical and histological impacts remain unclear. This study investigates the effects of chronic meat-based and PBM burger consumption on metabolic and organ health, considering sex differences. Thirty-six Wistar rats (18 males and 18 females) were divided into three groups: control (standard chow), meat burger-fed, and PBM burger-fed. Improved chow was prepared using lyophilized burger powder. Over eight weeks, food intake, weight gain, and food efficiency ratio (FER) were monitored. Serum biochemical markers, including AST, ALT, urea, creatinine, lipid profile (TG, CHOL, HDL, LDL), and leptin, were analyzed, alongside histopathological evaluation of the liver, kidneys, and heart. PBM-fed rats exhibited significantly higher FER than the meat group (p < 0.05). AST and ALT levels were slightly elevated in meat-fed rats, while PBM-fed males had increased urea levels. Triglyceride levels were significantly higher in the meat group, but cholesterol levels did not differ significantly. Serum leptin was elevated in both experimental groups, suggesting leptin resistance. Histological findings showed mild hepatic inflammation and microvacuolar changes, with minor cardiac fibrosis. These findings highlight the need for further research on PBM’s long-term health effects.
Background/Objectives: UBC demonstrates a relatively low prevalence in patients under 50 years old. Our study aimed to compare the pathological characteristics of UBC in young and elderly patients and to assess the age-related variations in these characteristics. Methods: This retrospective study from January 2018 to December 2022 encompassed 762 patients with an initial diagnosis of UBC. To evaluate the pathological characteristics of UBC in young patients, compared to elderly patients, we divided our cohort using a cut-off age of 50 years. Additionally, to evaluate the age-dependent variations in these characteristics, we further stratified our patients into three age groups (≤50, 51–70, and >70 years old). Results: Of the 762 patients included in our study, 37 (4.86%) were young (≤50 years old), with a median age of 44 and a M:F ratio of 3.11:1. Conventional UC was the most common histology (86.5%). Regarding tumour grade, we noticed a higher prevalence of PUNLMP (10.8% versus 2.3%) and LGPUC (45.9% versus 37.1%) and a lower prevalence of HGPUC (43.2% versus 60%) and CIS (0% versus 0.6%) in young patients (p = 0.008). In this group, the pTa stage revealed a higher prevalence (64.9% versus 46.8%), while pT1 and pT2 showed a lower prevalence (32.1% versus 18.9% and 20.6% versus 16.2%) (p = 0.179). All results remained consistent when the cohort was stratified into three age groups, showing age-related variations (p = 0.001 and p = 0.089, respectively). Conclusions: In young patients, UBC tends to be of a lower grade and stage compared to elderly patients, and these characteristics demonstrate a gradual age-related stratification.
Background/Objectives: Chronic heart failure (CHF) remains a significant global health burden, with high morbidity, prolonged hospitalizations, and increased mortality. Traditional biomarkers such as NT-proBNP provide prognostic value; however, novel biomarker ratios may enhance risk stratification. This study evaluated the predictive utility of the NT-proBNP-to-albumin ratio (NTAR), red cell distribution width-to-eGFR ratio (RGR), and red cell distribution width-to-fibrinogen ratio (RFR) for hospital length of stay (LOS), extended hospitalization (ELOS), in-hospital mortality, and 6-month all-cause mortality. Methods: A retrospective observational pilot study was conducted on 382 CHF admissions (2022–2024) with comprehensive laboratory assessment. Biomarker performance was assessed through uni- and multivariate logistic regression, receiver operating characteristic curve, and Cox proportional hazards stepwise methods of analyses for refining predictive models. Results: NTAR and RGR emerged as significant predictors of hospitalization outcomes. NTAR demonstrated a moderate correlation with prolonged LOS (r = 0.45, p < 0.001) and was an independent predictor of ELOS (AUC = 0.697, OR = 2.438, p < 0.001), outperforming NT-proBNP. Additionally, NTAR significantly predicted in-hospital mortality (AUC = 0.768, OR = 4.461, p < 0.001) and 6-month all-cause mortality (AUC = 0.766, OR = 4.185, p < 0.001). RGR was the strongest predictor of in-hospital mortality (AUC = 0.785, HR = 2.18, p = 0.005), highlighting its role in renal dysfunction and erythropoietic alterations in CHF. The RFR observed prognostic value was minimal. Conclusions: In our study, NTAR and RGR offered valuable prognostic value underscoring the interplay of cardiac stress, nutritional status, and renal function in CHF prognosis. Further multicenter validation is warranted for these biomarkers.
Background: In 2016, the SAGER (sex and gender equity in research) guidelines were developed to standardize research reporting and to facilitate the generalizability of research findings for women and men, thereby impacting clinical practice.
Objectives: To assess the extent to which the SAGER guidelines have been implemented in neurosurgical publications.
Methods: Original research articles from leading neurosurgical journals indexed in Google Scholar under the category ‘Neurosurgery’ were examined and assessed for the extent to which the articles conformed to the SAGER guidelines. Data were extracted on subjects (sample size and relative proportions of sex or gender) and on adherence to the SAGER guidelines (one item for general principles and five items from recommendations for each section of the article) and summarized.
Results: We included 98 articles from 10 leading neurosurgical journals. The average number of subjects for a journal was 4728, of which 2056 (43.5%) were women. Only nine (9.2%) of the 98 articles used the terms ‘sex’ and ‘gender’ appropriately. The outcomes were disaggregated by sex in 16 (16.3%) articles; sex differences were acknowledged in the introduction in six (6.1%) articles; considered in the ‘Methods’ section in five (5.1%) articles; the differing numbers of women and men were justified in the methods in two (2%) articles; and the generalizability of the results to women or men was discussed in five (5.1%) articles. The journals showed no differences in the extent to which they adhered to the guidelines.
Conclusions: Reporting sex and gender equity in neurosurgical journals is negligible for the most screened SAGER items as is the endorsement of the guidelines. The results likely reflect the lack of awareness of both the importance of disaggregating data by sex or gender and the existence of pertinent guidelines.
Data mining and natural language processing (NLP) are fundamental fields that interact in many ways. Text mining shares many topics, such as sentiment analysis and content understanding. Combining these two fields enables more efficient mining of text data and the extraction of valuable information. In particular, the GAN (Generative Adversarial Network) architecture has achieved success in image generation and has started to be used on text data. However, training GANs is fraught with difficulties due to the complexity of text data. Linguistic studies show important differences between languages. Language is characterized by fluidity, ambiguity, and context‐sensitive interpretations, and text‐generating GAN models can struggle to deal with these complexities. The interaction between data quality, language structure, and complex interpretation can lead to inconsistency and ambiguity in the text production of GAN models. These problems are particularly pronounced when complexities such as semantic subtleties, idiomatic expressions, and context‐dependent usages come into play. Text generation is an area of GAN models used in NLP to generate language and enrich text‐based applications. Work in this area can contribute to analyzing, classifying, and processing text data. Many methods and techniques have been proposed to improve the performance of text GANs. However, some problems may be encountered in the optimization of these methods. Therefore, it is essential to use optimized methods. In conclusion, GANs can be an important tool to improve text generation in NLP. Still, they require continuous research and innovation to deal with factors such as language complexity and data quality.
Background/Objectives: Non-communicable diseases (NCDs) are the leading cause of preventable morbidity and mortality globally. To reduce the prevalence of NCDs, the World Health Organization issued guidelines for a healthy lifestyle, which have been adopted in various countries. Our study aimed to evaluate the dietary habits of the ethnic Hungarian population of Romania, allowing us to identify potential differences in nutritional behavior compared to the country’s general population. Methods: A cross-sectional, observational, questionnaire-based study was conducted to collect information on eating behavior, food purchasing habits, and dietary patterns among ethnic Hungarians, the largest minority group in Romania. The obtained data were interpreted using multivariate data analysis (MVDA), including principal component analysis models (PCA-X) to establish pattern recognition and data clustering, and orthogonal partial least squares discriminant analysis (OPLS-DA) models to examine class differences between the identified clusters. Results: A total of 247 valid questionnaires were evaluated; the most represented groups were females (67.2%), young adults aged 18 to 30 (56.3%), individuals with normal body mass index (54.7%), and those with a higher education level (45.7%). Health-conscious purchasing and eating behaviors were more characteristic of middle-aged and older adults, females, and those with a higher education level. Young adults appear to have a more varied diet, but overconsumption of unhealthy food products and a lack of interest in healthy dietary habits is evident. Conclusions: Appropriate nutritional education is necessary for all age groups; however, programs targeting young adult Hungarians are especially important, as most expressed little interest in healthy eating habits. Further research examining the underlying relationship between dietary habits and cultural factors as well as socio-economic factors could offer new opportunities to promote a healthy lifestyle.
Pyoderma gangrenosum (PG) is a debilitating inflammatory skin condition characterized by painful, necrotic ulcers, significantly impairing patient quality of life. The variability in clinical outcomes and the lack of standardized treatment protocols challenge effective PG clinical management and research. The Understanding Pyoderma Gangrenosum, Review and Assessment of Disease Effects (UPGRADE) project seeks to address this gap by establishing a core outcome set (COS) for PG clinical trials. UPGRADE has reached consensus on three core outcome domains: Pain, Quality of Life, and Clinical Signs. Here we describe a protocol detailing the next steps of UPGRADE’s COS development to employ an international multistakeholder modified Delphi consensus process to reach consensus on the content of each core domain through the identification and definition of core domain-specific domain items. The process outlined in this protocol will involve generating domain items from the existing literature, refining these items through iterative e-Delphi surveys, and finalizing them in a consensus meeting. This work will enhance the granularity of these domains and facilitate more precise outcome measurement in clinical trials. The development of these detailed domain items is crucial for standardizing outcome reporting across PG trials, thereby improving research quality and enabling better treatment strategies, ultimately enhancing patient outcomes.
Background: The first trimester of pregnancy is known for its proinflammatory state, so it is considered a challenging period due to increased maternal vulnerability to viral infections. The main purpose of the current study was to evaluate the incidence trend of early miscarriages and whether there was any possible influence of the COVID-19 pandemic on pregnancy outcomes. Materials and Methods: We conducted a retrospective cohort study in which we included all pregnant women who had been admitted to our hospital between January 2018 and December 2022. Our aim was to compare the percentage of early miscarriages occurring in the pre-pandemic period (January 2018–February 2020) and during the pandemic (March 2020–December 2022). We decided to measure the total number and percentage of early pregnancy outcomes, including all viable pregnancies, ectopic pregnancies, and both medical and spontaneous abortions. Results: The annual incidence of registry-identified early miscarriages declined from 5.4% of 12–46-year-old women in 2018 to 3.6% in 2022 (p = 0.008). An overall incidence rate of 3.66% [95% C.I. 3.26–4.05] was calculated, with 4.25% [95% C.I. 3.35–4.41] in the pre-pandemic period and 3.24% [95% C.I. 2.82–3.57] during the pandemic. The highest incidence rate (p < 0.0001) was identified among nulliparous women (36.9%). Conclusions: To conclude, this study proved that the increase in the early miscarriage incidence rate could be assigned to an advanced maternal age, irrespective of one’s reproductive history. This study proved that no significant increase in the incidence rate of early miscarriage during the COVID-19 pandemic was noted, suggesting that this viral infection does not alter the risk of miscarriages. We hope that these findings help women deal with emotional stress and offer them reassurance about bearing children during pandemic periods.
Background/Objectives: Cervical cancer primarily disseminates through the lymphatic system, with the metastatic involvement of pelvic and para-aortic lymph nodes significantly impacting prognosis and treatment decisions. Sentinel lymph node (SLN) mapping is critical in guiding surgical management. However, resource-limited settings often lack advanced detection tools like indocyanine green (ICG). This study evaluated the feasibility and effectiveness of SLN biopsy using alternative techniques in a high-risk population with a high prevalence of large tumours. Methods: This prospective, observational study included 42 patients with FIGO 2018 stage IA1–IIA1 cervical cancer treated between November 2019 and April 2024. SLN mapping was performed using methylene blue alone or combined with a technetium-99m radiotracer. Detection rates, sensitivity, and false-negative rates were analysed. Additional endpoints included tracer technique comparisons, SLN localization patterns, and factors influencing detection success. Results: SLNs were identified in 78.6% of cases, with bilateral detection in 57.1%. The combined technique yielded higher detection rates (93.3% overall, 80% bilateral) compared to methylene blue alone (70.4% overall, 40.7% bilateral, p < 0.05). The sensitivity and negative predictive values were 70% and 93.87%, respectively. Larger tumours (>4 cm), deep stromal invasion, and prior conization negatively impacted detection rates. False-negative SLNs were associated with larger tumours and positive lymphovascular space invasion. Conclusions: SLN biopsy is feasible in resource-limited settings, with improved detection rates using combined tracer techniques. However, sensitivity remains suboptimal due to a steep learning curve and challenges in high-risk patients. Until a high detection accuracy is achieved, SLN mapping should complement, rather than replace, pelvic lymphadenectomy in high-risk cases.
Despite decades of intense preclinical and clinical research, currently available antiarrhythmic strategies yield disappointing results over the long-term, as they are often ineffective and have a high side-effect profile (Ehrlich and Nattel, Drugs 69:757–74, 2009). This is at least partially due to the complexity of cardiac arrhythmias pathophysiology and to a still incomplete understanding of the fundamental mechanisms underlying them.
In different stages of development, from neonates to infants, toddlers, school-age children, and adolescents, there are important differences regarding drug absorption, distribution, metabolism, and elimination that ultimately lead to different dosage regimens, and a higher risk of adverse effects in very young children. These differences are multifactorial, ranging from physiological changes to diet, and sometimes different drug formulations. Antiarrhythmic treatment in children brings two important issues that must be addressed: adapting doses and, secondly, the lack of studies in the pediatric population. Currently, for some antiarrhythmic drugs, the dosage regimens used in the pediatric population are still heterogenous.
Background/Objectives: Molar–incisor hypomineralization (MIH) is a prevalent dental condition characterized by hypomineralized enamel affecting the first permanent molars and incisors. It leads to visible enamel opacities, with varying severity. Children with MIH often experience dental hypersensitivity, which can result in increased dental fear and anxiety, complicating dental treatment. Salivary cortisol, a well-established biomarker of stress, has been used to assess stress levels in various pediatric conditions but has not been extensively studied in MIH. This study aimed to assess salivary cortisol levels as a stress biomarker in children with MIH and compare them to those in children without MIH. Methods: Sixty children aged 5–9 years were divided into two groups: 31 with MIH and 29 healthy controls. Salivary cortisol levels were measured using ELISA, and statistical analysis was performed using IBM SPSS software, version 23 The Mann–Whitney test was used for group comparison, and the Kruskal–Wallis test evaluated the correlation between MIH severity and cortisol levels. Results: Children with MIH showed significantly higher mean cortisol levels (2.63 ng/mL) compared to controls (0.96 ng/mL), with a p-value of 0.0001. A progressive increase in cortisol levels was observed with the severity of MIH, with the highest levels recorded in grade 3 (4.38 ng/mL), in contrast to grade 0 (0.95 ng/mL), with a p-value of 0.001. Conclusions: Salivary cortisol levels are significantly higher in children with MIH, suggesting that MIH-related stress may contribute to dental anxiety and hypersensitivity. These findings highlight the importance of stress management in pediatric dental care.
The relationship between neuroinflammation and depression is a complex area of research that has garnered significant attention in recent years. Neuroinflammation, characterized by the activation of glial cells and the release of pro-inflammatory cytokines, has been implicated in the pathophysiology of depression. The relationship between neuroinflammation and depression is bidirectional; not only can inflammation contribute to the onset of depressive symptoms, but depression itself can also exacerbate inflammatory responses, creating a vicious cycle that complicates treatment and recovery. The present comprehensive review aimed to explore the current findings on the interplay between neuroinflammation and depression, as well as the mechanisms, risk factors, and therapeutic implications. The mechanisms by which neuroinflammation induces depressive-like behaviors are diverse. Neuroinflammation can increase pro-inflammatory cytokines, activate the hypothalamus–pituitary–adrenal (HPA) axis, and impair serotonin synthesis, all of which contribute to depressive symptoms. Furthermore, the activation of microglia has been linked to the release of inflammatory mediators that can disrupt neuronal function and contribute to mood disorders. Stress-induced neuroinflammatory responses can lead to the release of pro-inflammatory cytokines that not only affect brain function but also influence behavior and mood. Understanding these mechanisms is crucial for developing targeted therapies that can mitigate the effects of neuroinflammation on mood disorders.
Congenital diaphragmatic hernia (CDH) is a relatively rare and severe developmental disease. Even with the most recent multidisciplinary therapies, the risk for neonatal mortality and morbidity remains high. Recent advancements in prenatal treatments, alongside experimental and clinical data, suggest that fetoscopic endoluminal tracheal occlusion (FETO) promotes lung development and offers a promising strategy against lung hypoplasia and pulmonary hypertension. It is the only existing direct mechanical therapy that intervenes in the regulation of pulmonary pressure. Its influence on lung development also interferes with tissue homeostasis and cell differentiation; it also enhances inflammation and apoptosis. Its physiopathology on cellular and molecular levels is still poorly understood. Unfortunately, the procedure also carries significant pregnancy-, maternal-, and fetus-related risks. Assessing a multifaceted intervention requires a collective view of all aspects. This scoping review uncovers potential materno-fetal procedure-related risks and highlights innovative solutions. Future research on lung development therapies in CDH may focus on the “dual hit” mechanism, combining molecular-targeting drugs and regenerative medicine with the mechanical nature of FETO for synergistic effects.
Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) are public health concerns worldwide. These two diseases share the same pathophysiological and genetic similarities. This study aimed to investigate the T2DM known single nucleotide polymorphisms (SNPs) of the adiponectin C1Q and collagen domain containing (ADIPOQ), cyclin-dependent kinase inhibitor 2A and 2B (CDKN2A/2B), and signal sequence receptor subunit 1 (SSR1) genes in a cohort of Romanian GDM pregnant women and perinatal outcomes. DNA was isolated from the peripheral blood of 213 pregnant women with (n = 71) or without (n = 142) GDM. Afterward, ADIPOQ (rs266729), CDKN2A/2B (rs10811661), and SSR1 (rs9505118) gene polymorphisms were genotyped using TaqMan Real-Time PCR analysis. Women with GDM had a higher pre-pregnancy body mass index (BMI) (p < 0.0001), higher BMI (p < 0.0001), higher insulin resistance homeostatic model assessment (IR-HOMA) (p = 0.0002), higher insulin levels (p = 0.003), and lower adiponectin levels (p = 0.004) at birth compared to pregnant women with normoglycemia. GDM pregnant women had gestational hypertension (GH) more frequently during pregnancy (p < 0.0001), perineal lacerations more frequently during vaginal birth (p = 0.03), and more macrosomic newborns (p < 0.0001) than pregnant women from the control group. We did not find an association under any model (allelic, genotypic, dominant, or recessive) of ADIPOQ rs266729, CDKN2A/2B rs10811661, and SSR1 rs9505118 polymorphisms and GDM. In correlation analysis, we found a weak positive correlation (r = 0.24) between the dominant model GG + CG vs. CC of rs266729 and labor induction failure. In the dominant model TT vs. CC + CT of rs10811661, we found a weak negative correlation between this model and perineal lacerations. Our results suggest that the ADIPOQ rs266729, the CDKN2A/2B rs10811661, and the SSR1 rs9505118 gene polymorphisms are not associated with GDM in a cohort of Romanian pregnant women.
Background
Synchronous occurrence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is extremely rare.
Case
A 67‐year‐old male was admitted to the hospital with hemoperitoneum caused by a liver mass rupture and elevated serum liver enzymes. Abdominal magnetic resonance imaging revealed a solid mass, with 38 mm in maximum diameter, located in the fifth/sixth segments of the liver, suggesting an HCC. Emergency surgery was performed and a second liver mass in the fourth segment was identified intraoperatively, with 20 mm in maximum diameter. Hepatic resection of the affected segments was performed with free resection margins. Histopathological examination revealed the synchronous occurrence of HCC and ICC with a predominant ductal plate malformation pattern. The patient is still alive at 41 months after its first surgery.
Conclusions
In patients with HCC, a proper intraoperative assessment is indicated, in addition to imaging investigations, to detect synchronous lesions that can change the therapeutic approach. This is the first case ever reported in the literature in which synchronous HCC and ICC with a predominant ductal plate malformation pattern were incidentally diagnosed in a patient with hemoperitoneum.
Atrial fibrillation (AF) causes a heavy socio-economic burden on healthcare systems around the globe. Identification of new preventive, diagnostic, and treatment methods is imperative. In recent years, special attention has been paid to microRNAs (miRNAs) as potential regulators of AF pathogenesis. Through post-transcriptional regulation of genes, miRNAs have been shown to play crucial roles in AF-related structural and electrical atrial remodeling. Altered expression of different miRNAs has been related to proarrhythmic changes in the duration of action potentials and atrial fibrosis. In clinical studies, miRNA changes have been associated with AF, whereas in experimental studies miRNA manipulation has emerged as a potential therapeutic approach. It would appear that, with the advent of miRNAs, we may have found the Holy Grail, and that efficient and personalized AF therapy may be one step away. Yet, the clinical relevance of miRNA evaluation and manipulation remains questionable. Studies have identified numerous miRNAs associated with AF, but none of them have shown sufficient specificity for AF. MicroRNAs are not gene-specific but regulate the expression of a myriad of genes. Cardiac and non-cardiac off-target effects may thus occur following miRNA manipulation. A Pandora’s box might thus have opened with the advent of these sophisticated molecules. In this paper, we provide a critical analysis of the clinical and experimental, epidemiological and mechanistic data linking miRNAs to AF, we discuss the most promising miRNA therapeutic approaches, we emphasize a number of questions that remain to be answered, and we identify hotspots for future research.
Background and Objectives: Peripheral nerve defect regeneration is subject to ongoing research regarding the use of conduits associated with various cells or molecules. This article aims to correlate histopathological and clinical outcomes at the end of a 12-week experiment performed on a rat sciatic nerve model and show which repair method has the best results. Materials and Methods: Forty male Wistar rats were divided into four groups to compare the results of four different methods of reconstruction for sciatic nerve defect: (1) nerve graft–control group, (2) empty aortic conduit, (3) aortic conduit filled with platelet-rich plasma (PRP) and (4) aortic conduit filled with mesenchymal stem cells. There were three clinical examinations: a sensitivity test, a mobility test and a footprint test. After 12 weeks, the nerves were excised and assessed microscopically using conventional Hematoxylin and Eosin staining (HE), special stains and immunohistochemistry (IHC). Results: Nerve regeneration was observed in all batches, both from the clinical and histopathological assessment; the two types of examinations correlated for each batch. Immunohistochemistry and special staining offered a more complete image of the nerve regeneration results. Conclusions: Superior nerve regeneration was achieved using an aortic conduit in combination with either PRP or stem cells, while the empty aortic conduit recorded lesser results.
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