University of Medicine and Pharmacy of Craiova

We conducted a multicenter, observational, post-marketing, real-world cohort study in Romania that included all patients with MS (PwMS) who completed at least one cycle of CLD with at least three months of follow-up as of September 2024. Demographic variables and MS clinical characteristics regarding each patient were recorded. No Evidence of Disease Activity (NEDA-3) was assessed at one and two years after CLD initiation. The primary outcome was the proportion and characteristics of PwMS achieving NEDA-3 at 12 and 24 months after CLD initiation and the identification of predictors of failure in achieving NEDA-3. A total of 348 PwMS cases were included, of which CLD was the first DMT option in 129 (37.1%). At one year, 76.74% of the patients with complete available data fulfilled all criteria, achieving NEDA-3 status, with similar proportions between previously DMT-treated PwMS and naïve PwMS. In the univariate analysis, the onset of long-tract involvement, as compared to infratentorial (OR = 6.32, p = 0.01), and the number of Gd-enhancing lesions (OR = 1.12, p = 0.02), were significantly associated with increased odds of not achieving NEDA-3 at one year. In the multivariate model, long tracts (OR = 10.28, p = 0.006), higher baseline EDSS (OR = 1.39, p = 0.01), and longer disease duration (OR = 0.92, p = 0.04) were independent predictors. The initiation of CLD treatment was associated with achieving NEDA-3 at one year in >70% of cases. CLD demonstrated an improvement in MS control, irrespective of the patients' demographics, RMS history, or prior DMT exposure. CLD treatment has a favorable safety profile and a high level of patient adherence.

Life almost certainly began as chemistry long before the appearance of cells and genes. In this pre-cellular phase (Chemical Life), metastable reaction networks would have required mechanisms that increase the persistence of fragile intermediates, bias reaction pathways, and enable stepwise accumulation under non-equilibrium cycling. Here we propose that boron (B), through pH-dependent speciation and reversible interactions with polyhydroxylated substrates, can act as an effective chemical scaffold for ribonucleic acid (RNA)-relevant precursor chemistry. Under mildly alkaline and low water activity regimes (e.g., films, gels, evaporitic/brine microenvironments, and mineral interfaces), borate can reversibly associate with cis -diol motifs in sugars, favoring furanosyl forms (including ribose) and reducing degradative side reactions; in related settings, borate–sugar interactions can also help bias phosphate-transfer reactions toward improved regioselectivity. These roles address key constraints on prebiotic sugar persistence and phosphate availability/reactivity in bulk water. To operationalize when such effects are most plausible, we introduce the Boron Availability Index (BAI) as a heuristic, test-design metric integrating B speciation with environmental modifiers (water activity, ionic strength/competition, mineral buffering, and transport/exchange). We highlight an intermediate proposed test window (BAI ≈0.2–0.4, heuristic) where sugar stabilization, phosphorylation directionality, and network persistence can be jointly evaluated by controlled variation of physicochemical parameters. We therefore frame the Boron Theorem as a conditional, falsifiable constraint within RNA world-compatible pathways: environments that sustain B in a reactive, water-soluble form (borate) under suitable geochemical context are more likely to support Chemical Life by increasing the persistence and directional reactivity of ribose–phosphate intermediates.

Background/Objectives: Hepatitis E virus (HEV) infection is an increasingly recognized cause of acute hepatitis in Europe, but short-term in-hospital laboratory dynamics remain insufficiently described in hospitalized cohorts. We aimed to characterize admission biochemical abnormalities and paired admission-to-discharge laboratory changes in hospitalized patients with acute hepatitis E from Craiova, Romania, with exploratory sex- and age-stratified analyses. Methods: We conducted a single-center retrospective observational study including 40 consecutive hospitalized patients with acute hepatitis E during 2024-2025. Admission and discharge laboratory values were compared at the within-patient level, and exploratory subgroup analyses by sex and age class were performed. Given the limited sample size, multivariable analyses were restricted to parsimonious age-adjusted models for selected endpoints. Results: The cohort comprised 22 females (55%) and 18 males (45%), with a mean age of 53.05 ± 21.44 years; two in-hospital deaths occurred. At admission, marked transaminase elevation and frequent hyperbilirubinemia were observed, with 70% of patients having total bilirubin ≥ 2 mg/dL and 40% ≥ 10 mg/dL. During hospitalization, ALT and AST declined markedly, whereas total and direct bilirubin improved more modestly, indicating slower resolution of jaundice/cholestatic abnormalities. Platelets increased, while prothrombin index changes were heterogeneous. Male patients had higher bilirubin values at admission and discharge and more frequent clinically relevant hyperbilirubinemia thresholds; however, these findings should be interpreted cautiously given the small sample size, the retrospective design, and the absence of standardized clinical confounders and mechanistic data. Exploratory age-stratified analyses did not identify robust differences after multiplicity control. Conclusions: In hospitalized hepatitis E, hepatocellular injury markers improved rapidly during hospitalization, whereas cholestatic abnormalities resolved more slowly and often remained clinically relevant at discharge. The observed sex-related cholestatic pattern should be considered exploratory and requires confirmation in larger studies with standardized clinical covariates and longer follow-up. These findings support closer monitoring of bilirubin trajectories at discharge, particularly in male patients, and highlight the need for integrating laboratory dynamics into short-term clinical assessment of hospitalized HEV cases.

Medical oncology is a young specialty in Romania, where early-career oncologists face challenges related to training, mentorship, and research. This study explored their professional status and needs to inform workforce development. An online survey was conducted between February and April 2025 among physicians under 40 years of age who were members of the Romanian National Society of Medical Oncology (SNOMR). The questionnaire (60 items) covered demographics, employment, mentorship, research, and professional development. Descriptive analysis was performed. Of 456 eligible members, 169 responded (response rate: 37%). Most were residents based in oncology institutes or university hospitals. Job insecurity was common, with 57% on temporary contracts. Nearly all respondents (99%) had clinical duties, but only 21% engaged in research and 9% in teaching. Mentorship was inconsistently available (61% had a mentor), yet interest in structured programs was very high (88% for national and 87% for international initiatives). Research involvement was limited: 46% reported no activity, 85% lacked funding, and only 28% published in the past year. While over 80% expressed interest in fellowships or exchanges, only 16% had trained abroad. Most (85%) were ESMO members, but only half considered SNOMR support sufficient. Young oncologists in Romania are motivated but face significant barriers, including job instability, insufficient mentorship, and limited research opportunities. Expanding structured mentorship, ensuring protected research time, and strengthening international mobility are essential. Recent SNOMR initiatives represent important first steps toward addressing these gaps.

Vimentin expression as a prognostic marker in pancreatic cancer: a systematic review and meta-22 analysis 23 The authors apologize for this error and state that this does not change the scientific conclusions of 34 the article in any way. The original article has been updated.

The incorporation of plant-derived oils into cosmetic formulations has attracted increasing interest due to their natural origin, skin compatibility, and multifunctional formulation roles. Argan and castor oils are widely used in cosmetic products as emollient lipid components with intrinsic antioxidant properties. However, limited studies have systematically evaluated the physicochemical stability and antioxidant performance of emulsions combining these two oils. The aim of this study was to develop and comprehensively characterize a stable oil-in-water (O/W) cosmetic emulsion based on argan and castor oils using a natural non-ionic emulsifier (C14–22 Alcohol (and) C12–20 Alkyl Glucoside). Particular emphasis was placed on formulation stability, as it represents a critical prerequisite for further product evaluation. Stability was investigated through thermal stress testing (4–37 °C), centrifugation assays, droplet size analysis, and zeta potential measurements. Complementary physicochemical and structural characterization was performed using rheological analysis and Fourier transform infrared (FT-IR) spectroscopy. The formulated emulsion exhibited good physical stability with no phase separation under the tested conditions, a skin-compatible pH, a uniform droplet size distribution (4.15 ± 0.68 µm), and pseudoplastic, moderately thixotropic rheological behavior. Antioxidant capacity was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, yielding an IC50 value of 19.21 ± 1.02 mg/mL. Overall, this study provides a formulation-oriented framework for the development and evaluation of stable natural oil-based O/W emulsions intended for cosmetic applications, supporting future optimization and biological validation.

Background and Objectives: When a single missing tooth must be replaced, the best solution is the placement of an implant. In adults, most of the time the space for implant is totally or partially closed due to the shift in the adjacent teeth. The objective of the study was to describe the clinical parameters, treatment choices, and outcomes associated with orthodontic space opening for single-tooth implants in various treatment solutions, as well as to determine their influence on the variation in the dimension of the edentulous space. Materials and Methods: An observational prospective cohort study was designed in which patients with a single missing tooth were selected to be included in the study. After the clinical examination two groups were formed: patients who opted for fixed orthodontic treatment (metallic or sapphire) to open space for implant and patients who opted for alignment to achieve this (with Invisalign or Spark). All subjects received orthodontic treatment. A dental chart was created for each patient which included demographics, clinical data, orthopantomography (OPG), profile cephalograms, and photographs. The potential implant prosthetic space was measured during orthodontic treatment to observe the space dimension evolution in time. Results: In total, 97 patients were included in the study, 60 women and 37 men, with ages between 14 and 60 years. Edentulous spaces dimensions were opened from 1-4 mm to 5-6 mm (39.18% patients), 6-8 mm (48.45%), and >8 mm (12.37%). Both types of orthodontic treatments were effective in opening the potential prosthetic space for implant. Conclusions: Large prosthetic spaces and older edentulism tend to require longer treatments. Older patients had experienced edentulism for a longer period, indicating a correlation between age and the duration of tooth loss. Metal fixed orthodontic appliances were used in exceedingly long treatments, while aligners/sapphire brackets were used in short-medium durations. For the study group, fixed appliances and aligners proved to be effective in opening the space for future implants.

Ultra-processed foods (UPFs) represent a distinct dietary paradigm characterized by structurally simplified food matrices and chronic exposure to multiple additives, including emulsifiers, artificial sweeteners, and preservatives. Rather than acting in isolation, these compounds operate within a multi-additive environment that reshapes the gut ecosystem through convergent mechanisms. Emerging evidence suggests that additive-rich ultra-processed dietary environments may disrupt the gut ecosystem through three interconnected layers: (1) structural impairment of the intestinal barrier, including mucus erosion and tight-junction destabilization; (2) microbial metabolic shifts marked by short-chain fatty acid depletion, altered bile acid signaling, and enrichment of lipopolysaccharide-producing taxa; and (3) immune and inflammatory reprogramming promoting low-grade systemic inflammation. These processes collectively reduce ecosystem resilience-the capacity of the gut microbiota to resist and recover from perturbation. Vulnerability to additive-driven dysbiosis varies across the life course. During infancy, incomplete ecosystem stabilization may increase susceptibility to long-term ecological imprinting, whereas in older age, reduced microbial diversity and immune remodeling may impair recovery capacity following dietary stressors. In contrast, fiber-rich, minimally processed dietary patterns appear to enhance microbial resilience by reinforcing functional redundancy, metabolic buffering, and barrier integrity. Although much mechanistic evidence has been derived from experimental models, accumulating human data support the biological plausibility of additive-associated microbiota alterations. By integrating multi-additive exposure, ecosystem disruption, life-course modulation, and resilience within a unified framework, this review provides a mechanistically coherent model linking ultra-processed dietary environments to microbiota-mediated chronic disease risk. Here, we formalize this integrative perspective as the Three-Layer Ecosystem Disruption (TLED) Model.

Plant-derived extracellular vesicles (PDEVs), engineered phytosomes, bioinspired polymeric plant-based nanoparticles (PBNPs), hybrid phyto-inorganic nanocomposites, green-synthesized metal nanoparticles, self-assembled nanoarchitectures, and multifunctional composites represent a rapidly advancing class of sustainable, nature-inspired nanocarriers. These platforms combine exceptional biocompatibility, negligible immunogenicity, and renewable sourcing with tunable drug loading, targeted delivery, and controlled release properties. This review synthesizes translational advances from 2020 to 2026, covering scalable isolation/bioprocessing (bioreactors, elicitation), multi-parametric physicochemical/multi-omics characterization, rational engineering/hybridization, and rigorous in vitro/in vivo assessments of uptake, biodistribution, pharmacokinetic (PK), and efficacy. Phytosomes and PBNPs markedly enhance oral bioavailability and targeted delivery of lipophilic phytochemicals, while PDEVs offer unique immunomodulatory, anti-inflammatory, and gene-regulatory activities. Hybrid and green-synthesized systems provide structural stability, redox modulation, and synergistic effects, and self-assembled/multifunctional composites address solubilization barriers with stimuli-responsive design. Early-phase human studies on grapefruit-, ginger-, turmeric-, and ginseng-derived PDEVs report excellent short-term safety, favorable PK, and preliminary bioactivity signals, with no observed immunogenicity or dose-limiting toxicities; however, these trials remain exploratory, constrained by small sample sizes and safety-focused endpoints. Despite challenges, including methodological heterogeneity, variable yields, long-term safety uncertainties (notably for inorganic hybrids), and regulatory ambiguities, emerging strategies such as clustered regularly interspaced short palindromic repeats (CRISPR)-engineered plant line; artificial-intelligence-driven process optimization; standardized guidelines, and integrated clinical, intellectual property, and commercialization frameworks are progressively addressing these barriers. Collectively, these advances position plant-derived nanocarriers as immunologically privileged, eco-friendly alternatives to synthetic and mammalian platforms, laying the foundation for a sustainable era of precision phytomedicine.