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The clinical management of coronary artery disease and the prevention of acute coronary syndromes require knowledge of the underlying atherosclerotic plaque pathobiology. Hybrid imaging modalities capable of comprehensive assessment of biochemical and morphological plaques features can address this need. Here we report the first implementation of an intravascular catheter system combining fluorescence lifetime imaging (FLIm) with polarization-sensitive optical coherence tomography (PSOCT). This system provides multi-scale assessment of plaque structure and composition via high spatial resolution morphology from OCT, polarimetry-derived tissue microstructure, and biochemical composition from FLIm, without requiring any molecular contrast agent. This result was achieved with a low profile (2.7 Fr) double-clad fiber (DCF) catheter and high speed (100 fps B-scan rate, 40 mm/s pullback speed) console. Use of a DCF and broadband rotary junction required extensive optimization to mitigate the reduction in OCT performance originating from additional reflections and multipath artifacts. This challenge was addressed by the development of a broad-band (UV-visible-IR), high return loss (47 dB) rotary junction. We demonstrate in phantoms, ex vivo swine coronary specimens and in vivo swine heart (percutaneous coronary access) that the FLIm-PSOCT catheter system can simultaneously acquire co-registered FLIm data over four distinct spectral bands (380/20 nm, 400/20 nm, 452/45 nm, 540/45 nm) and PSOCT backscattered intensity, birefringence, and depolarization. The unique ability to collect complementary information from tissue (e.g., morphology, extracellular matrix composition, inflammation) with a device suitable for percutaneous coronary intervention offers new opportunities for cardiovascular research and clinical diagnosis.

Abstract Treatment planning parameters in radiotherapy are key elements that dictate the success of treatment outcome. While some parameters are commonly evaluated irrespective of cancer type, others are site-dependent and strongly patient specific. Given the critical influence of planning parameters on personalized therapy, the aim of this study was to evaluate the correlations between the dosimetric indices (conformity, homogeneity and mismatch indices) related to tumor coverage and the patient-specific parameters which encompass parameters pertaining to organs at risk (widths and lengths of heart and ipsilateral lung included in treatment fields, mean/maximum doses to heart, ipsilateral lung, left anterior descending aorta and contralateral breast) and tumor volume. Forty breast cancer patients were divided into two groups according to tumor location: twenty with left-sided (group A) and twenty with right-sided breast cancer (group B). Conformal (3DCRT), intensity modulated (IMRT) and volumetric arc modulated (VMAT) radiotherapy techniques were used for plan creation. Moderate to strong correlations were found for ipsilateral lung parameters for both groups of patients regardless of the treatment technique. Moderate to strong correlations were found for heart parameters in group A patients, while no correlations were observed in group B. The mismatch index presented moderate to strong correlations with tumor volume for all treatment techniques (r = -0.861 3DCRT, r = -0.556 IMRT, r = -0.533 VMAT) particularly in group A. The evaluated correlations indicate the role of dosimetric indices in personalized treatment planning.

Abstract Background Persistent inequities in breast cancer outcomes exist. Understanding women’s experiences along the care pathway is the first step to finding solutions to tackle these inequities. Methods Secondary data analysis of the 2017/2018 English National Cancer Patient Experience Survey (n = 25,408) using logistic regression to explore inequities in care experience by sociodemographic factors (age, ethnicity, socioeconomic position, sexual orientation) across 59 survey questions. We used the Candidacy Framework to interpret and organise our findings. Results Compared to older (65–74) and White British women, young (35-44, OR = 0.55 [0.44, 0.69]), Asian (OR = 0.52 [0.41, 0.67]), Black (OR = 0.67 [0.46, 0.97]) and White Other (OR = 0.63 [0.49, 0.81]) women were more likely to rate their overall care experience less positively, respectively. Similar findings were observed along all domains of the cancer pathway. Through a candidacy lens, we identified multilevel factors related to this variation including prolonged help-seeking behaviours (individual), poor patient-provider communication (interpersonal), and variation in access to healthcare professionals and resources (system level). Conclusion Multilevel factors influence inequities in the experience of care along the breast cancer pathway for young women and women from minoritised groups. Interventions are necessary to ensure cancer care systems are responsive to women’s health needs and provide equity of care to all patients.

Abstract The goal of this study is to improve methodologies that define the maturation of ovarian follicles and enhance in vitro fertilization by employing decellularized ovaries. Preantral follicles of mice were cultured for 14 days in both the decellularized ovary and two- dimensional (2D) conditions. The oocyte maturation rate, fertilization rate, and the subsequent embryo development rate were assessed in 2D and the decellularized ovary and compared to in vivo condition. Additionally, the gene expression profile of IGF1R, integrin α v β 3, Cox2, Caspase-3, Bax, and Bcl2 l1 was determined in blastocysts. The culture in the decellularized ovary showed a significantly higher number of MII oocytes in comparison to the 2D culture (P < 0.05). Compared to in vivo, both the 2D and the decellularized ovary cultures exhibited significantly lower percentages of MII oocytes, 2PN, two-cell, cleavage, and blastocyst (P < 0.05). In the decellularized ovary culture, significantly higher percentages of 2PN and blastocyst were observed (P < 0.05) compared to the 2D culture. The gene expression level of IGF1R and Cox2 in blastocysts from both the 2D and the decellularized ovary cultures was markedly lower compared to in vivo. However, the gene expression levels of Integrin α v and β 3 were comparable in blastocysts derived from in vivo and decellularized ovary-matured oocytes. Blastocysts derived from decellularized ovary-matured oocytes showed a higher bcl211 expression level compared to the blastocysts from 2D (P < 0.05). Employing decellularized ovarian tissues methodologies for in vitro maturation of oocytes provides a promising avenue towards generating embryos with improved implantation potential.

This study explores the complex relationships between various dimensions of eating behavior regulation and their impact on bulimia and food preoccupation using network analysis. The objective was to identify key regulatory mechanisms that influence bulimic behaviors and food-related obsessions. The study analyzed data from 659 participants, recruited via convenience sampling, using scales that measured intrinsic motivation, integrated regulation, identified regulation, introjected regulation, external regulation, amotivation, and bulimia and food preoccupation. Pearson’s correlation analysis revealed significant negative relationships between bulimia and both introjected regulation (r = −0.345, p < 0.001) and external regulation (r = −0.298, p < 0.001). Network analysis highlighted identified regulation and introjected regulation as central nodes with substantial influence over bulimia and food preoccupation, while integrated regulation demonstrated a significant indirect impact. The perception that food is necessary for life and energy, as well as for nourishment, enjoyment, social and cultural relationships, and emotional comfort, was further demonstrated using qualitative thematic analysis. The aforementioned results emphasize the pivotal functions of identified and introjected regulatory mechanisms in shaping conduct associated with food preoccupation and bulimia. According to the study, specific therapies that target these mechanisms may be essential for lowering bulimic symptoms and encouraging better eating practices.

Medical oncology, through conventional chemotherapy as well as targeted drugs, remains an important component of cancer patient management, particularly for systemic disease. Despite advances in all areas of medical oncology, certain challenges persist in the form of drug resistance and severe normal tissue toxicity. These unwanted effects can be counteracted through a patient-tailored treatment approach, which in chemotherapy is translated as pharmacogenomics. This research field investigates the way genetic makeup influences a patient’s response to various drugs with the aim to minimize trial-and-error associated with drug administration. The paper introduces the role, advances and challenges of pharmacogenomics, highlighting the importance of Big Data mining to reveal the mechanisms behind drug–gene pair interaction for better patient outcomes. International consortiums have prioritized their focus on the clinical implementation of pharmacogenomics while tackling the challenges ahead: data standardization, ethical aspects and the education of physicians and patients alike to comprehend the power of pharmacogenomics to transform medical oncology.

This Letter presents an experimental study comparing the photon rate and photon economy of pulse sampling fluorescence lifetime imaging (PS-FLIm) with the conventional time-correlated single photon counting (TCSPC) technique. We found that PS-FLIm has a significantly higher photon detection rate (200 MHz) compared with TCSPC (2-8 MHz) but lower photon economy (4-5 versus 1-1.3). The main factor contributing to the lower photon economy in PS-FLIm is laser pulse variability. These results demonstrate that PS-FLIm offers 25× faster imaging speed than TCSPC while maintaining room light rejection in clinical settings. This makes PS-FLIm a robust technique for clinical applications.

This study analyses the bioclimate of Cacica and Târgu Ocna resorts and of the salt mines on their territory, based on the Thermo-Hygrometric Index (THI). The bioclimate was analyzed based on hourly data (air temperature and relative humidity) from 2020-2022. The annual and diurnal regime of THI in the two resorts and the two underground salt mines were investigated and periods of bioclimatic comfort were identified. Thus, at Cacica, the comfort period covers the months of June-July-August and partly September, while at Târgu Ocna the period starts one month earlier (in May) and extends by one month compared to Cacica resort (until September). It is worth noting the presence of clusters of days or hours with thermal discomfort caused by heat, especially in Târgu Ocna (in July and August). Over the course of a day, bioclimatic comfort based on the THI index is reached in Cacica, during the summer, from 6.00 a.m. and lasts until midnight. In the transition months, April, May and October, comfort is felt between 11.00 a.m and 6.00. p.m. In Târgu Ocna the bioclimatic comfort is specific to summer throughout the day, with a more pronounced discontinuity in the afternoon hours, when the discomfort caused by the heat sets in. The salt mines benefit from a thermal stability that is reflected in the slightly variable THI values and in a slight cooling discomfort. The stable atmosphere and the microclimatic uniformity give Cacica and Trotuș salt mines certain balneoclimatic qualities recommended both for tourists and patients (with respiratory diseases).

SignificanceThis third biennial intraoperative molecular imaging (IMI) conference shows how optical contrast agents have been applied to develop clinically significant endpoints that improve precision cancer surgery.AimNational and international experts on IMI presented ongoing clinical trials in cancer surgery and preclinical work. Previously known dyes (with broader applications), new dyes, novel nonfluorescence-based imaging techniques, pediatric dyes, and normal tissue dyes were discussed.ApproachPrincipal investigators presenting at the Perelman School of Medicine Abramson Cancer Center's third clinical trials update on IMI were selected to discuss their clinical trials and endpoints.ResultsDyes that are FDA-approved or currently under clinical investigation in phase 1, 2, and 3 trials were discussed. Sections on how to move benchwork research to the bedside were also included. There was also a dedicated section for pediatric dyes and nonfluorescence-based dyes that have been newly developed.ConclusionsIMI is a valuable adjunct in precision cancer surgery and has broad applications in multiple subspecialties. It has been reliably used to alter the surgical course of patients and in clinical decision making. There remain gaps in the utilization of IMI in certain subspecialties and potential for developing newer and improved dyes and imaging techniques.

Challenges in identifying a glioblastoma's infiltrative edge during neurosurgical procedures result in rapid recurrence. A label-free fluorescence lifetime imaging (FLIm) device was used to evaluate glioblastoma's infiltrative edge in vivo in 15 patients (89 samples). FLIm data were analyzed according to tumor cell density, infiltrating tissue type (gray and white matter), and diagnosis history (new or recurrent). Infiltrations in white matter from new glioblastomas showed decreasing lifetimes and a spectral red shift with increasing tumor cell density. Areas of high versus low tumor cell density were separated through a linear discriminant analysis with a ROC-AUC=0.74. Current results support the feasibility of intraoperative FLIm for real-time in vivo brain measurements and encourage refinement to predict glioblastoma infiltrative edge, underscoring the ability of FLIm to optimize neurosurgical outcomes.

Identifying isocitrate dehydrogenase (IDH)-mutation and glioma subtype during surgery instead of days later can aid in modifying tumor resection strategies for better survival outcomes. We report intraoperative identification of IDH-mutant glioma (N = 12 patients) with a clinically compatible fluorescence lifetime imaging (FLIm) device (excitation: 355 nm; emission spectral bands: 390/40 nm, 470/28 nm, 542/50 nm). The fluorescence-derived parameters were analyzed to study the optical contrast between IDH-mutant tumors and surrounding brain tissue. IDH-mutant oligodendrogliomas exhibited shorter lifetimes (3.3 ± 0.1 ns) than IDH-mutant astrocytomas (4.1 ± 0.1 ns). Both IDH-mutant glioma subtypes had shorter lifetimes than white matter (4.6 ± 0.4 ns) but had comparable lifetimes to cortex. Lifetimes also increased with malignancy grade within IDH-mutant oligodendrogliomas (grade 2: 2.96 ± 0.08 ns, grade 3: 3.4 ± 0.3 ns) but not within IDH-mutant astrocytomas. The current results support the feasibility of FLIm as a surgical adjuvant for identifying IDH-mutant glioma tissue.

The present study addresses the issue in its title, starting from the definition of the general concepts of ethics and deontology, continuing with some regulations from Romania that concern norms of university ethics and deontology, their violations and procedural aspects in the case of finding the commission of such acts - their analysis being carried out from the perspective of the form of legal liability incurred, then, making an examination of the existing factual situation in this matter in the Republic of Moldova, highlighting the similarities and differences between some of the regulations of the two states mentioned above, and passing, finally, to the presentation of the conclusions drawn from the entire analysis carried out within the study. Particular attention was paid to the issue of the originality of the doctoral thesis and especially to the issue of plagiarism, examined including in correlation with copyright, the problem of the difficulties in detecting signs of plagiarism in some situations and the inequity in its detection, as well as the issue of the legal consequences of the detection of the existence of plagiarism, including in terms of the procedures carried out after the respective finding, from the perspective of the framework law currently in force, the drafting of which also took into account the CCR jurisprudence in relation to the way of resolving a notification regarding the suspicion of plagiarism on a doctoral thesis following the presentation of which the author was awarded the title of doctor. Last but not least, the present study, the elaboration of which involved, among other things, the consultation of relevant materials from the specialised literature, includes, in addition to highlighting the superior quality of some current regulations, several critical observations of the author, in consideration of which he formulated appropriate de lege ferenda proposals.

The aim of this study was to determine the degree of liver fibrosis with the help of a non-invasive method - transient elastography - in a long term monitored HIV-HBV coinfected group of patients (from the former Romanian pediatric cohort) and to assess the implication of various factors as potential risk factors for the development of liver fibrosis. We have reviewed a total of 636 patients (Px) that were in the evidence of the HIV Department of the “Victor Babes” Hospital of Infectious Diseases of Craiova, from which we randomly selected a group of 37 patients that are monthly attending the HIV department. Mean age of the patients was 34.03±2 years old and they were monitored for a long period of time, mean duration of monitorization was 26.11±4.31 years. Patients have been split into group A (13 Px) with various degrees of liver fibrosis and group B (24 Px) without liver fibrosis; the mean value of liver stiffness was higher in group A vs group B 11.27±5.72 vs.4.93±0.98 kPa, p

Microbial resistance is a rapidly escalating phenomenon worldwide, with complex mechanisms and important involvement in the determinants of healthcare-associated and in-hospital infections. At European level, it is estimated that 80.000 hospitalised patients have at least one HAI every day with multi-antimicrobial resistant germs, leading to an extension of hospital stay by 16 million days every year. In high-income countries, the prevalence is around 7.5%, and in low- and middle-income countries, the prevalence ranges from 5.7% to 19.2%. Material and method. Through a retrospective, descriptive study carried out in the Clinc Emergency Hospital ,,Prof.Dr. Nicolae Oblu” in Iasi, Romania in the period 2020-2021, the 602 identified and reported intra-hospital infections were investigated, focusing on the etiology and microbial resistance of the pathogens involved.Results. The most frequent etiological agents of HAI identified in our study were K. pneumoniae (13.45%), A. calcoaceticus (10.11%), S. aureus (8.45%), E. coli (7.62%), P. aeruginosa (5.47%), noting the predominance of Gram-negative bacteria (GN) and the fact that they are part of the ESKAPE group of pathogens, the percentages obtained being similar to the European average. Klebsiella pneumoniae (13.45 %) was the most common in the aetiological palette of HAIs, allowing us to highlight certain peculiarities regarding its antimicrobial resistance.Conclusions. The present study provides useful data for monitoring the resistance of pathogens involved in HAIs at hospital level, for guiding antibiotic therapy in healthcare-associated infections and for substantiating the implementation of a set of measures related to antibiotic therapy and antibiotic prophylaxis.

In general terms, neoplastic conditions are characterized by increasing in cell proliferation and decreasing in cell apoptosis. The multiplication of atypical neoplastic cells, through their invasive capacity, leads to the infiltration of tissues or organs through the bloodstream or the lymphatic system. In this context, chemotherapy remains one of the most used treatment modalities, contrary to the progress made in recent years regarding the management of cancer in the Oro-Maxillo-Facial (OMF) sphere. This is applied either alone or associated with other therapeutic methods to block abnormal cell proliferation. The great inconvenience of chemotherapy is the lack of selectivity because it acts both on tumor cells and normal cells in the body. The oral cavity is very vulnerable to the direct and indirect toxic effects of chemotherapy. This fact is primarily due to local peculiarities that include: a high rate of mucosal cell turnover, the presence of a complex and diverse microflora in the oral cavity as well as the small traumatic injuries present as a result of the exercise of normal oral functions (mastication, swallowing, phonation).

SignificanceCartilage tissue engineering is a promising strategy for effective curative therapies for treatment of osteoarthritis. However, tissue engineers depend predominantly on time-consuming, expensive, and destructive techniques as quality control to monitor the maturation of engineered cartilage. This practice can be impractical for large-scale biomanufacturing and prevents spatial and temporal monitoring of tissue growth, which is critical for the fabrication of clinically relevant-sized cartilage constructs. Nondestructive multimodal imaging techniques combining fluorescence lifetime imaging (FLIm) and optical coherence tomography (OCT) hold great potential to address this challenge.AimThe feasibility of using multimodal FLIm-OCT for nondestructive, spatial, and temporal monitoring of self-assembled cartilage tissue maturation in a preclinical mouse model is investigated.ApproachSelf-assembled cartilage constructs were developed for 4 weeks in vitro followed by 4 weeks of in vivo maturation in nude mice. Sterile and nondestructive in situ multispectral FLIm and OCT imaging were carried out at multiple time points ( t=2 , 4, and 8 weeks) during tissue development. FLIm and 3D volumetric OCT images were reconstructed and used for the analysis of tissue biochemical homogeneity, morphology, and structural integrity. A biochemical homogeneity index was computed to characterize nonhomogeneous tissue growth at different time points. OCT images were validated against histology.ResultsFLIm detects heterogenous extracellular matrix (ECM) growth of tissue-engineered cartilage. The outer edge of the tissue construct exhibited longer fluorescence lifetime in 375 to 410 and 450 to 485 nm spectral channels, indicating increase in collagen content. Significant ( p

Considering a growing, aging population, the need for interventions to improve the healthspan in aging are tantamount. Diet and nutrition are important determinants of the aging trajectory. Plant-based diets that provide bioactive phytonutrients may contribute to offsetting hallmarks of aging and reducing the risk of chronic disease. Researchers now advocate moving toward a positive model of aging which focuses on the preservation of functional abilities, rather than an emphasis on the absence of disease. This narrative review discusses the modulatory effect of nutrition on aging, with an emphasis on promising phytonutrients, and their potential to influence cellular, organ and functional parameters in aging. The literature is discussed against the backdrop of a recent conceptual framework which describes vitality, intrinsic capacity and expressed capacities in aging. This aims to better elucidate the role of phytonutrients on vitality and intrinsic capacity in aging adults. Such a review contributes to this new scientific perspective—namely—how nutrition might help to preserve functional abilities in aging, rather than purely offsetting the risk of chronic disease.

The research paper aims to build a composite index of the financial performance of companies, to find if the impact of the COVID-19 crisis was significantly positive for most manufacturing companies listed on Bucharest Stock Exchange, and to look if the manufacturing companies were resilient being prepared with savings that could have mitigate the effects of this pandemic crisis. The results of the FE model selected show that 31.67% of the company’s equity variation is justified by the two independent variables, the stronger correlation of equity being with reserves. Based on the composite index of financial performance built, the manufacturing companies were grouped in three clusters: a cluster with low financial performance companies (z < 4), a cluster with good financial performance companies (4 ≤ z ≤ 8) and a cluster with high financial performance companies (z > 8). The third cluster groups the most analysed companies, on which the pandemic crisis had a positive impact, which achieved the highest financial performance; they are those companies that “take advantage” from the COVID-19 crisis, adapting their business strategy to the market conditions imposed. The article adds value to the specialty literature by building the financial performance’s composite indicator, clustering the manufacturing companies by financial performance’ Z-score.

Key Clinical Message In contrast to previously thought, arrhythmogenic cardiomyopathy can occur exclusively in the left ventricle in association with autosomal dominant mutation, even without any skin manifestations. Abstract We present a case of a 43‐year‐old male with left ventricle (LV)‐predominant arrhythmogenic cardiomyopathy (ACM) caused by a novel p.Q1830 mutation in the desmoplakin (DSP) gene. The patient had a significant family history of sudden cardiac death (SCD) and presented with presyncope and exertional dyspnea. The patient's electrocardiography (ECG) showed frequent premature ventricular complexes (PVCs) with bigeminy and couplet patterns. Cardiac magnetic resonance imaging (CMR) revealed late gadolinium enhancement of the left ventricle (LV) and ventricular systolic dysfunction, suggesting LV‐predominant arrhythmogenic cardiomyopathy. The patient was started on guideline‐directed medical therapy (GDMT), and an implantable cardioverter‐defibrillator (ICD) was implanted for primary prevention. The patient reported significant improvement in his heart failure symptoms at the 2‐year follow‐up. The article highlights the importance of timely diagnosis with multimodality imaging and genetic testing and management of the rare DSP‐related LV‐predominant ACM associated with a high risk of SCD.