Search Results (12,087)

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article

Objective: The accurate visualization of root canal systems on periapical radiographs is critical for successful endodontic treatment. This study aimed to evaluate and compare the effectiveness of several image enhancement algorithms—including a novel Total Variation–Contrast-Limited Adaptive Histogram Equalization (TV-CLAHE) technique—in improving the detectability of root canal configurations in mandibular incisors, using cone-beam computed tomography (CBCT) as the gold standard. A null hypothesis was tested, assuming that enhancement methods would not significantly improve root canal detection compared to original radiographs. Method: A retrospective analysis was conducted on 60 periapical radiographs of mandibular incisors, resulting in 420 images after applying seven enhancement techniques: Histogram Equalization (HE), Contrast-Limited Adaptive Histogram Equalization (CLAHE), CLAHE optimized with Pelican Optimization Algorithm (CLAHE-POA), Global CLAHE (G-CLAHE), k-Caputo Fractional Differential Operator (KCFDO), and the proposed TV-CLAHE. Four experienced observers (two radiologists and two dentists) independently assessed root canal visibility. Subjective evaluation was performed using an own scale inspired by a 5-point Likert scale, and the detection accuracy was compared to the CBCT findings. Quantitative metrics including Peak Signal-to-Noise Ratio (PSNR), Signal-to-Noise Ratio (SNR), image entropy, and Structural Similarity Index Measure (SSIM) were calculated to objectively assess image quality. Results: Root canal detection accuracy improved across all enhancement methods, with the proposed TV-CLAHE algorithm achieving the highest performance (93–98% accuracy), closely approaching CBCT-level visualization. G-CLAHE also showed substantial improvement (up to 92%). Statistical analysis confirmed significant inter-method differences (p < 0.001). TV-CLAHE outperformed all other techniques in subjective quality ratings and yielded superior SNR and entropy values. Conclusions: Advanced image enhancement methods, particularly TV-CLAHE, significantly improve root canal visibility in 2D radiographs and offer a practical, low-cost alternative to CBCT in routine dental diagnostics. These findings support the integration of optimized contrast enhancement techniques into endodontic imaging workflows to reduce the risk of missed canals and improve treatment outcomes. Full article

Objectives: Diabetes Mellitus involves demanding challenges that interfere with family functioning and routines. In turn, family and social context impacts individual glycemic control. This study aims to identify this recursive interplay, the mutual influences of family systems and diabetes management. Design: Data was collected through a cross-sectional design comparing patients, aged 22–55, with and without metabolic control. Methods: Participants filled out a set of self-report measures of sociodemographic, clinical and family systems assessment. Patients (91) were also invited to describe their perception about disease management interference regarding family functioning. We first examined the extent to which family variables grouped dataset to determine if there were similarities and dissimilarities that fit with our initial diabetic groups’ classification. Results: Cluster analysis results identify a two-cluster solution validating initial classification of two groups of patients: 49 with metabolic control (MC) and 42 without metabolic control (NoMC). Independent sample tests suggested statistically significant differences between groups in family subscales- family difficulties and family communication (p < 0.05). Binary logistic regression shed light on predictors of explained variance to no metabolic control, in four models: Sociodemographic, Clinical data, SCORE-15/Congruence Scale and Eating Behavior. Furthermore, groups differ on family support, level and sources of family conflict caused by diabetes management issues. Considering only patients who co-habit with a partner for more than one year (N = 44), NoMC patients score lower on marital functioning in all categories (p < 0.05). Discussion: Family-Chronic illness interaction plays a significant role in a patient’s adherence to treatment. This study highlights the Standards of Medical Care for Diabetes, considering caregivers and family members on diabetes care. Full article

Constipation is a prevalent gastrointestinal disorder that significantly impairs quality of life. While pharmacological agents such as loperamide are widely used to induce constipation in experimental models, there is increasing interest in natural alternatives for alleviating intestinal dysfunction. In this study, we investigated the laxative effects of soybean powder fermented by Bacillus subtilis DKU_09 in a loperamide-induced rat model of constipation. The probiotic strain was isolated from cheonggukjang, a traditional Korean fermented soybean paste, and its identity was confirmed through 16S rRNA sequencing. Fermented soybean powder was characterized morphologically via scanning electron microscopy and chemically via HPLC to assess its isoflavone content. Rats were administered loperamide (5 mg/kg) for four days to induce constipation and were then treated with fermented soybean powder at doses of 100, 200, or 300 mg/kg. No pharmacological laxatives (e.g., PEG) were used as a positive control; instead, values from the treatment groups were compared with those from the loperamide-only constipation group. Key outcomes of fecal output, water content, colonic fecal retention, and gastrointestinal transit ratio were measured. The fermented product significantly improved stool frequency and moisture content, reduced colonic fecal retention, and restored gastrointestinal transit in a dose-dependent manner. Notably, the 300 mg/kg group demonstrated nearly complete recovery of fecal parameters without affecting body weight. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. These findings suggest that Bacillus subtilis-fermented soybean powder exerts synergistic laxative effects through the combined action of probiotic viability and fermentation-enhanced bioactive compounds such as aglycone isoflavones. This study supports the potential use of fermented soybean-based nutraceuticals as a natural and safe intervention for constipation and gastrointestinal dysregulation. Full article

Background: Patients in Intensive Care Units (ICUs) often develop non-thyroidal illness syndrome. Potentially, thyroid hormones may be removed during continuous veno-venous hemodiafiltration (CVVHDF), as their molecular size is smaller than the filter pores’ cutoff. The study’s main aim was to assess whether the serum concentration of thyroid hormones changes over time during CVVHDF. Methods: This was a prospective observational trial that included 30 patients treated in an ICU. All patients developed acute kidney injury (AKI) and had clinical indications for implementation of CVVHDF. Blood samples were collected before initiation of CVVHDF and at 1, 2, 3, 6, 9 and 12 days after. The last sample was collected three days after CVVHDF withdrawal. Thyroid function was evaluated by determining the serum concentration of TSH, thyrotropin-releasing hormone (TRH), free triiodothyronine (fT₃), free thyroxine (fT₄), total triiodothyronine (tT₃), total thyroxine (tT₄) and reverse triiodothyronine (rT₃). We additionally calculated the total activity of peripheral deiodinases (G_D) using a mathematical model. Results: TRH and TSH levels remained mostly within normal ranges. fT4 and tT4 were in normal range or slightly below. In contrast, fT3 and tT3 were undetectably low in most patients throughout. Reverse T3 levels remained within normal limits. There were no statistically significant changes in any thyroid hormone levels over the CVVHDF treatment period. The calculated peripheral G_D activity was lower than normal, but importantly, it did not change significantly over time. Conclusions: Thyroid hormones are not lost due to hemodiafiltration. Decreased deiodinases activity is responsible for alterations in serum concentrations of thyroid hormones in patients during CVVHDF. Full article

Background/Objectives: Neoadjuvant radiochemotherapy and perioperative chemotherapy are both well-established treatment strategies for locally advanced adenocarcinoma of the esophagus (EAC) and the esophagogastric junction (AEGJ). However, recent knowledge controversially discusses whether neoadjuvant radiotherapy or perioperative chemotherapy represents superior therapeutic options to prolong survival or cause less toxicity. Methods: We retrospectively analyzed 76 patients with locally advanced EAC or AEGJ treated at our tertiary cancer center between January 2015 and March 2023. Patients received either perioperative FLOT chemotherapy (n = 36) or neoadjuvant radiochemotherapy following the CROSS protocol (n = 40), followed by surgical resection and standardized follow-up. We compared survival outcomes, toxicity profiles, treatment compliance, and surgical results between the two groups. Results: There were no statistically significant differences between FLOT and CROSS treatments in five-year loco-regional controls (LRC: 61.5% vs. 68.6%; p = 0.81), progression-free survival (PFS: 33.9% vs. 42.8%; p = 0.82), overall survival (OS: 60.2% vs. 63.4%; p = 0.91), or distant controls (DC: 42.1% vs. 56.5%; p = 0.39). High-grade hematologic toxicities did not significantly differ between groups (p > 0.05). Treatment compliance was lower in the FLOT group, with 50% (18/36) not completing all the planned chemotherapy cycles, compared to 17.5% (7/40) in the CROSS group. All the patients in the CROSS group received the full radiotherapy dose. Surgical outcomes and post-surgical tumor status were comparable between the groups. Conclusions: Although perioperative chemotherapy with FLOT has recently become a standard of care for locally advanced EAC and AEGJ, neoadjuvant radiochemotherapy per the CROSS protocol remains a well-tolerated alternative. In appropriately selected patients, both approaches yield comparable oncological outcomes. Full article

Drought stress is a major environmental constraint that significantly reduces wheat productivity worldwide. In this study, seventeen wheat genotypes were evaluated under well-watered and drought-stressed conditions across two consecutive years (2023–2024) in a controlled greenhouse experiment. Twenty morphological and agronomic traits were recorded, and their responses to prolonged water limitation were assessed using multivariate statistical methods, including three-way ANOVA, principal component analysis (PCA), and cluster analysis. Drought stress significantly decreased all traits except the harvest index (HI), with the most severe reductions observed in traits related to secondary spikes (e.g., grain weight reduced by 95%). The ANOVA results confirmed significant genotype × treatment (G × T) interactions for key agronomic traits, with the strongest effect observed for total grain weight (F = 7064.30, p < 0.001). A PCA reduced the 20 original variables to five principal components, explaining 87.2% of the total variance. These components reflected distinct trait groups associated with productivity, spike architecture, and development in phenology. Cluster analysis based on PCA scores grouped genotypes into three clusters with contrasting drought response profiles. A yield-based evaluation confirmed the cluster structure, distinguishing genotypes with a stable performance (average yield loss ~58%) from highly sensitive ones (~70% loss). Overall, the findings demonstrate that drought tolerance in wheat is governed by complex trait interactions. Integrating a trait-based multivariate analysis with a yield stability assessment enables the identification of genotypes with superior adaptation to water-limited environments, providing an excellent genotype background for future breeding efforts. Full article

The frequency of specific variants associated with the risk of developing cardiovascular diseases has been extensively studied through genome-wide association studies (GWASs). Differences between populations may be caused by the interaction of several factors, such as environmental and genetic backgrounds. Here, we studied 19 SNPs involved in atherosclerosis (AT) and venous thromboembolism (VTE) risk in the Azorean and mainland Portuguese populations and compared their frequencies with other European, Asian, and African populations. Results revealed that, although there was no difference between Azorean and mainland populations, eight SNPs in ADAMTS7, PCSK9, APOE, and LDLR genes showed significant statistical differences (χ², p < 0.05) when compared with the European population. The multilocus genetic profile (MGP) analysis demonstrated that 7.4% of mainlanders and 11.2% of Azoreans have a high-risk of developing atherosclerosis. The opposite tendency was observed for venous thromboembolism risk, where the mainland population presented a higher risk (6.5%) than the Azorean population (4.1%). Significant differences in VTE-MGP distribution were found among the Azorean geographic groups (p < 0.05), with the Eastern group showing the highest VTE risk. Conversely, for the risk AT-MGP, the Central group shows the highest risk (12.9%). Taken together, the data suggest a risk of developing a cardiovascular disease consistent with the European population. However, the Azorean-specific genetic background and socio-cultural habits (dietary and sedentary) may explain the differences observed, validating the need to assess the allelic and genotypic frequencies between different populations, especially in small geographical locations, such as the Azores archipelago. In conclusion, these findings can improve the prevention, diagnosis, and treatment of high-risk individuals, and contribute to reducing the lifelong burden of cardiovascular diseases in the Azorean population. Full article

Background/Objectives: This single-cohort follow-up study describes the median overall survival (OS) in patients with unresectable head and neck squamous cell carcinoma (HNSCC) due to invasion of vital structures, which is under-represented in the current literature. Secondarily, subgroups were evaluated according to the type of presentation, in order to identify clinical characteristics and contribute to developing an appropriate treatment plan and managing patient’s expectations. Methods: This single-cohort observational study analysed the OS of 39 patients from the Otolaryngology Department with advanced-stage head and neck cancer with invasion of vital anatomical structures considered ineligible for surgical treatment. Secondarily, subgroups were evaluated according to type of presentation and various clinical characteristics. Results: A total of 39 patients radiologically classified as having unresectable HNSCC (i.e., unsuitable for surgical resection), with a mean age of 66.87 years, were included during a 24-month follow-up. By the end of the study, 56.4% of the patients had died. The median OS was 16.09 months. Statistically significant differences were observed when comparing human papilloma virus (HPV)-positive and -negative status and when comparing initial and recurrent tumours. Conclusions: The invasion of anatomical structures such as the skull base, internal carotid artery, and prevertebral space was associated with a marked decrease in survival, with an OS time of 16 months. This study provides valuable evidence in patients with unresectable HNSCC, highlighting tumour recurrence and HPV-negative status as important indicators of poor prognosis. Full article

Glioma is a type of neoplasia that spontaneously arises from the glial cells of the brain in humans and dogs, and its prognosis is grave. Current treatment options for glioma include surgery, radiation therapy, chemotherapy, or symptomatic treatment. Evidence has shown that cannabidiol (CBD) may have anticancer, anti-angiogenic, and anti-inflammatory properties in both in vitro and in vivo studies. In this in vivo murine experiment, the canine glioma cell line J3TBG was injected into the frontoparietal cortex of immunodeficient mice using xenogeneic tissue transplantation. A total of 20 mice were randomly assigned to one of four treatment groups—Control group (C), CBD group (CBD), Radiation Therapy group (RT), and CBD plus Radiation Therapy group (CBD + RT). After transplantation of J3TBG, a single fraction of 5.5 Gy RT was administered to the RT and CBD + RT groups, and CBD was administered daily to the CBD and CBD + RT groups. Necropsies were performed to collect blood and brain tissue. Although there was not a statistically significant difference, the survival time among mice were longer in the CBD + RT group than the RT group. These results indicate that CBD may be used as an adjunctive therapy to enhance RT treatment. Larger cohort studies are required to substantiate the hypothesis. Full article

Climate change has a significant negative impact on agriculture and food production. This trend requires technological development and the adaptation of new technologies in both the grapevine production and winemaking sectors. High temperatures and heat accumulation during the growing season result in faster ripening and a higher sugar content, leading to a higher alcohol content during fermentation. The negative consequences are an imbalanced wine character and consumer reluctance, as lower alcoholic beverages are now in high demand. Over the last decade, several methods have been developed to handle this impact and reduce the alcohol content of wines. In this study, we used the MASTERMIND^® REMOVE membrane-based dealcoholization system to reduce the alcohol concentration in of Pinot gris wines from 12.02% v/v to 10.69% v/v and to investigate the effect on analytical parameters in three steps (0.5%, 1%, and 1.5% reductions) along the treatment. To evaluate the impact of the partial alcohol reduction and identify correlations between the wine chemical parameters, data were analyzed with ANOVA, PCA, multivariate linear regression and cluster analysis. The results showed that except for the extract, sugar content and proline content, the treatment had a significant effect on the chemical parameters. Both free and total SO₂ levels were significantly reduced as well as volatile acid, glycerol and succinic acid levels. It must be highlighted that some parameters were not differing significantly between the untreated and the final wine, while the change was statistically verified in the intermediate steps of the partial alcohol reduction. This was the case for example for n-Propanol, i-Amylalcohol, Acetaldehyde, and Ethyl acetate. The multivariate linear regression model explained 18.84% of the total variance, indicating a modest but meaningful relationship between the alcohol content and the investigated analytical parameters. Our results showed that even if the applied instrument significantly modified some of the wine chemical parameters, those changes would not influence significantly the wine sensory attributes. Full article

Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ² = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania’s shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program. Full article

Introduction: Lichen sclerosus (LSc) is a chronic, progressive, inflammatory skin disease that primarily affects the anogenital region in both sexes and across all age groups. Aim: To investigate the relationship between quality of life (QoL) and disease severity, as measured by a newly developed Lichen Sclerosus Score (LSc score), with respect to anatomical site before and after 12 weeks of treatment. Methods: A total of 136 patients diagnosed with LSc (88 men, 48 women) were enrolled between March and September 2022. Patients were clinically evaluated using the LSc score and completed the Dermatology Life Quality Index (DLQI). Treatment was individualized based on clinical findings and history. At 12 weeks, both clinical assessment and DLQI were repeated. Results: LSc scores significantly decreased following treatment (p < 0.001), except in the female subgroup. In men, LSc scores were strongly correlated with DLQI scores both before (r = 0.709; p < 0.001) and after (r = 0.492; p < 0.001) treatment. Among women, a significant correlation was found only before treatment (r = 0.457; p < 0.001). Significant associations were identified between LSc score and DLQI items 1, 8, and 9 in men and the overall cohort. No statistically significant differences in LSc scores or DLQI were observed across anatomical sites after correction for multiple comparisons. Conclusions: Disease severity in genital LSc is closely associated with QoL impairment. This is, to our knowledge, the first study to examine the correlation between a clinical severity score and DLQI. While anatomical site did not significantly affect scores, certain sites may have a disproportionate impact, underscoring the complex ways in which LSc affects patients’ lives. Full article

Background/Objectives: The expansion of National Health Insurance (NHI) coverage for dental implants in South Korea has substantially increased implant placements among older adults. While implants offer functional and esthetic benefits, their lack of periodontal ligaments alters occlusal force distribution, potentially increasing biomechanical stress on adjacent or opposing teeth. This study aimed to investigate the association between the increased number of dental implants and the incidence of cracked teeth following the introduction of implant insurance. Methods: A retrospective analysis was conducted using the Clinical Data Warehouse of Seoul St. Mary’s Dental Hospital. Patients who underwent molar crown restorations between 2014 and 2022 were included. The incidence and clinical features of cracked teeth were compared before (2014–2015) and after (2016–2022) the introduction of implant insurance. Statistical analyses assessed differences in symptom presentation, pulp status, and treatment outcomes. Results: Among 5044 molars restored with crowns, 1692 were diagnosed with cracks. The incidence of cracked teeth significantly increased after NHI coverage for implants (25.5% vs. 32.6%, p < 0.001). Cases after insurance implementation showed fewer signs and symptoms at initial presentation (67.4% vs. 50.0%, p < 0.001), reduced irreversible pulpitis (37.2% vs. 25.8%, p < 0.001), and increased preservation of pulp vitality (46.9% vs. 57.8%, p < 0.001). These shifts may reflect changes in occlusal adjustment practices and earlier clinical intervention. Conclusions: The findings suggest a temporal link between increased implant placement and the rising incidence of cracked teeth. Implant-induced occlusal changes may contribute to this trend. Careful occlusal evaluation and follow-up are essential after implant placement, and further prospective studies are warranted to confirm causality and refine prevention strategies. Full article

Background/Objectives: Immediate dentin sealing (IDS) has been widely investigated in sound dentin; however, its efficacy on demineralized dentin remains insufficiently explored. This in vitro experimental study aimed to evaluate the shear bond strength (SBS) of indirect composite resin restorations bonded to demineralized dentin using IDS, assessed at 24 h and after 6 months of aging. Methods: Twenty-five extracted premolars were randomly divided into five groups: (1) control (no sealing), (2) IDS applied to sound dentin (sound-IDS), (3) IDS applied to demineralized dentin (carious-IDS), (4) delayed dentin sealing (DDS) on sound dentin (sound-DDS), and (5) DDS on demineralized dentin (carious-DDS). SBS values were analyzed using a three-way analysis of variance (ANOVA) with dentin condition (sound vs. demineralized), aging time (24 h vs. 6 months), and sealing strategy (control, IDS, DDS) as independent variables. Statistical analyses were performed using SigmaPlot 12.0, with significance set at p < 0.05. Results: The results showed that IDS led to significantly higher SBS than DDS (p < 0.05). Bond strength was significantly influenced by dentin condition (p < 0.05), and all interactions between variables—particularly between dentin condition and sealing strategy, and between aging time and treatment—were statistically significant (p < 0.001). Overall, bond strength was higher at 24 h than after 6 months. IDS showed optimal performance in sound dentin, while DDS resulted in better long-term outcomes in demineralized dentin. Conclusions: These findings suggest that DDS may be the more effective approach in cases of carious or demineralized dentin. Full article