Search Results (9)

Background: Anterior cruciate ligament reconstruction (ACLR) using double adjustable fixation gained popularity in the last decade due to its minimally invasive technique. However, suspensory fixation devices could be related to recurrent instability, poor clinical outcomes, and patient dissatisfaction. The present study aims to evaluate the clinical outcomes following ACLR using double adjustable-loop suspensory fixation devices in the demanding population of young patients. Methods: Between 2019 and 2022, 95 patients with knee post-traumatic anterior cruciate ligament insufficiency were treated with primary ACLR using semitendinosus quadrupled graft and double adjustable-loop suspensory fixation devices and followed for at least two years. Concomitant lesions were also treated at the same surgical time. The knee examination form of the International Knee Documentation Committee (IKDC) was used to assess clinical evaluation, and the return to physical activities using the Tegner Activity Scale was recorded. Patient-reported objective measures (PROMs) were also evaluated, including the IKDC subjective and Lysholm scores. Results: Sixty-six males and twenty-nine females with a mean age of 23.8 (range 18–37) and a mean BMI of 24.9 (SD ± 2.42) kg/m² were included in this study. All patients were evaluated clinically as normal or nearly normal at the final follow-up. PROMs also significantly improved postoperatively (p < 0.05) compared to the preoperative values. The Tegner Activity Scale increased from 2 to 7, the IKDC mean score improved from 43.9 (±8.9) to 93.3 (±12.3), and the modified Lysholm from 47.3 (±11.1) to 92.9 (±16.6). No complications or adverse events were recorded. Conclusions: Anterior cruciate ligament reconstruction utilizing double adjustable-loop suspensory fixation devices provides good clinical and functional outcomes in young patients at a two-year follow-up. Full article

Background: Multiple vaccinations have potential inimical effects on the immune system aging process. We examined whether response to SARS-CoV-2 vaccination with Tozinameran is associated with immunosenescence and immunoexhaustion in kidney transplant recipients (KTRs). Methods: In this prospective observational study, we observed 39 adult kidney transplant recipients (KTRs) who had no pre-existing anti-SARS-CoV-2 antibodies and were on stable immunosuppression. CD4+ and CD8+ T-cell subpopulations [comprising CD45RA+CCR7+ (naïve), CD45RA−CCR7+ (T-central memory, TCM), CD45RA−CCR7− (T-effector memory, TEM) and CD45RA+CCR7− (T-effector memory re-expressing CD45RA, T_EMRA, senescent), CD28− (senescent) and PD1+ (exhausted)] were evaluated at 2 time points: T1 (48 h prior to the 3rd), and T2 (3 weeks following the 3rd Tozinameran dose administration). At each time point, patients were separated into Humoral and/or Cellular Responders and Non-Responders. Results: From T1 to T2, CD4+TCM and CD8+TEM were increased, while naïve CD4+ and CD8+ proportions were reduced in the whole cohort of patients, more prominently among responders. At T2, responders compared to non-responders had higher CD8+CD28+ [227.15 (166) vs. 131.44 (121) cells/µL, p: 0.036], lower CD4+CD28− T-lymphocyte numbers [59.65 (66) cells/µL vs. 161.19 (92) cells/µL, p: 0.026] and percentages [6.1 (5.5)% vs. 20.7 (25)%, p: 0.04]. Conclusion: In KTRs, response to vaccination is not associated with an expansion of senescent and exhausted T-cell concentrations, but rather with a switch from naïve to differentiated-activated T-cell forms. Full article

Gemcitabine (2′,2′-difluoro-2′-deoxycytidine), a widely used anticancer drug, is considered a gold standard in treating aggressive pancreatic cancers. Gamma-proteobacteria that colonize the pancreatic tumors contribute to chemoresistance against gemcitabine by metabolizing the drug to a less active and deaminated form. The gemcitabine transporters of these bacteria are unknown to date. Furthermore, there is no complete knowledge of the gemcitabine transporters in Escherichia coli or any other related proteobacteria. In this study, we investigate the complement of gemcitabine transporters in E. coli K-12 and two common chemoresistance-related bacteria (Klebsiella pneumoniae and Citrobacter freundii). We found that E. coli K-12 has two high-affinity gemcitabine transporters with distinct specificity properties, namely, NupC and NupG, whereas the gemcitabine transporters of C. freundii and K. pneumoniae include the NupC and NupG orthologs, functionally indistinguishable from their counterparts, and, in K. pneumoniae, one additional NupC variant, designated KpNupC2. All these bacterial transporters have a higher affinity for gemcitabine than their human counterparts. The highest affinity (K_M 2.5–3.0 μΜ) is exhibited by NupGs of the bacteria-specific nucleoside-H⁺ symporter (NHS) family followed by NupCs (K_M 10–13 μΜ) of the concentrative nucleoside transporter (CNT) family, 15–100 times higher than the affinities reported for the human gemcitabine transporter hENT1/SLC29A1, which is primarily associated with gemcitabine uptake in the pancreatic adenocarcinoma cells. Our results offer a basis for further insight into the role of specific bacteria in drug availability within tumors and for understanding the structure–function differences of bacterial and human drug transporters. Full article

Two semi-quantitative, Luminex-based, single-antigen bead (SAB) assays are available to detect anti-HLA antibodies and evaluate their reactivity with complement binding. Sera from 97 patients with positive panel reactive antibody tests (>5%) were analyzed with two SAB tests, Immucor (IC) and One-Lambda (OL), for anti-HLA antibody detection and the evaluation of their complement-binding capacity. IC detected 1608/8148 (mean fluorescent intensity (MFI) 4195 (1995–11,272)) and 1136/7275 (MFI 6706 (2647–13,184)) positive anti-HLA class I and II specificities, respectively. Accordingly, OL detected 1942/8148 (MFI 6185 (2855–12,099)) and 1247/7275 (MFI 9498 (3630–17,702)) positive anti-HLA class I and II specificities, respectively. For the IC assay, 428/1608 (MFI 13,900 (9540–17,999)) and 409/1136 (MFI 11,832 (7128–16,531)) positive class I and II specificities bound C3d, respectively. Similarly, OL detected 485/1942 (MFI 15,452 (9369–23,095)) and 298/1247 (MFI18,852 (14,415–24,707)) C1q-binding class I and II specificities. OL was more sensitive in detecting class I and II anti-HLA antibodies than IC was, although there was no significant difference in the number of class II specificities per case. MFI was higher for complement vs. non-complement-binding anti-HLA antibodies in both assays. Both methods were equal in detecting complement-binding anti-HLA class I antibodies, whereas the C3d assay was more sensitive in detecting complement-binding anti-HLA class II antibodies. Full article

Background: Hereditary cancer predisposition syndromes are responsible for approximately 5–10% of all diagnosed cancer cases. In order to identify individuals at risk in a cost-efficient manner, family members of individuals carrying pathogenic alterations are tested only for the specific variant that was identified in their carrier relative. The purpose of this study was to investigate the clinical use and implementation of cascade family testing (CFT) in families of breast cancer patients with pathogenic/likely pathogenic variants (PVs/LPVs) in cancer-related predisposition genes. Methods: Germline sequencing was carried out with NGS technology using a 52-gene panel, and cascade testing was performed by Sanger sequencing or MLPA. Results: In a cohort of 1785 breast cancer patients (families), 20.3% were found to have PVs/LPVs. Specifically, 52.2%, 25.1%, and 22.7% of patients had positive findings in high-, intermediate-, and low-penetrance breast cancer susceptibility genes, respectively. Although CFT was recommended to all families, only 117 families (32.3%) agreed to proceed with genetic testing. Among the first-degree relatives who underwent CFT, 70.3% were female, and 108 of 121 (89.3%) were cancer free. Additionally, 42.7%, 36.7%, and 20.6% were offspring, siblings, and parents of the subject, respectively. Our data suggest that CFT was mostly undertaken (104/117, 88.8%) in families with positive findings in high-risk genes. Conclusions: Cascade family testing can be a powerful tool for primary cancer prevention by identifying at-risk family members. It is of utmost importance to implement genetic counseling approaches leading to increased awareness and communication of genetic testing results. Full article

Background and Aim: Immune status profile can predict response to vaccination, while lymphocyte phenotypic alterations represent its effectiveness. We prospectively evaluated these parameters in kidney transplant recipients (KTRs) regarding Tozinameran (BNT162b2) vaccination. Method: In this prospective monocenter observational study, 39 adult KTRs, on stable immunosuppression, naïve to COVID-19, with no protective humoral response after two Tozinameran doses, received the third vaccination dose, and, based on their immunity activation, they were classified as responders or non-responders. Humoral and cellular immunities were assessed at predefined time points (T₀: 48 h before the first, T₁: 48 h prior to the third and T₂: three weeks after the third dose). Results: Responders, compared to non-responders, had a higher total and transitional B-lymphocyte count at baseline (96.5 (93) vs. 51 (52)cells/μL, p: 0.045 and 9 (17) vs. 1 (2)cells/μL, p: 0.031, respectively). In the responder group, there was a significant increase, from T₀ to T_1, in the concentrations of activated CD4+ (from 6.5 (4) to 10.08 (11)cells/μL, p: 0.001) and CD8+ (from 8 (19) to 14.76 (16)cells/μL, p: 0.004) and a drop in CD3+PD1+ T-cells (from 130 (121) to 30.44 (25)cells/μL, p: 0.001), while naïve and transitional B-cells increased from T₁ to T₂ (from 57.55 (66) to 1149.3 (680)cells/μL, p < 0.001 and from 1.4 (3) to 17.5 (21)cells/μL, p: 0.003). The percentages of memory and marginal zone B-lymphocytes, and activated CD4+, CD8+ and natural killer (NK) T-cells significantly increased, while those of naïve B-cells and CD3+PD1+ T-cells reduced from T₀ to T₁. Conclusions: Responders and non-responders to the third BNT162b2 dose demonstrated distinct initial immune cell profiles and changes in cellular subpopulation composition following vaccination. Full article

B and T lymphocytes demonstrate important alterations in patients with systemic lupus erythematous (SLE), with a significant upregulation of double negative (DN) B cells. The aim of this study was to evaluate the correlation of T cell immunity changes with the distinct B-cell-pattern SLE. In the present study, flow cytometry was performed in 30 patients in remission of SLE and 31 healthy controls to detect DN B cells (CD19+IgD-CD27-) and a wide range of T lymphocyte subpopulations based on the presence of CD45RA, CCR7, CD31, CD28, and CD57, defined as naive, memory, and advanced differentiated/senescent T cells. Both B and T lymphocytes were significantly reduced in SLE patients. However, the percentage of DN B cells were increased compared to HC (12.9 (2.3–74.2) vs. 8 (1.7–35), p = 0.04). The distribution of CD4 and CD8 lymphocytes demonstrated a shift to advanced differentiated subsets. The population of DN B cells had a significant positive correlation with most of the early differentiated T lymphocytes, CD4CD31+, CD4CD45RA+CD28+, CD4CD45RA+CD57-, CD4CD45RA-CD57-, CD4CD28+CD57-, CD4CD28+CD57+, CD4 CM, CD8 CD31+, CD8 NAÏVE, CD8CD45RA-CD57-, CD8CD28+CD57-, and CD8CD28+CD57+. Multiple regression analysis revealed CD4CD31+, CD8CD45RA-CD57-, and CD8CD28+CD57- cells as independent parameters contributing to DN B cells, with adjusted R² = 0.534 and p < 0.0001. The predominance of DN B cells in patients with SLE is closely associated with early differentiated T lymphocyte subsets, indicating a potential causality role of DN B cells in T lymphocyte activation. Full article

End-stage renal disease (ESRD) is followed by alterations in adaptive immunity. The aim of this study was to evaluate B lymphocyte subtypes in ESRD patients before and after hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Patients and Methods. CD5, CD27, BAFF, IgM and annexin were evaluated by flow cytometry on CD19+ cells in ESRD patients (n = 40), at time of initiating HD or CAPD (T0) and 6 months later (T6). Results. A significant reduction in ESRD-T0 compared to controls was noticed for CD19+, 70.8 (46.5) vs. 171 (249), p < 0.0001, CD19+CD5−, 68.6 (43) vs. 168.9 (106), p < 0.0001, CD19+CD27−, 31.2 (22.1) vs. 59.7 (88.4), p < 0.0001, CD19+CD27+, 42.1 (63.6) vs. 84.3 (78.1), p = 0.002, CD19+BAFF+, 59.7 (37.8) vs. 127.9 (123.7), p < 0.0001 and CD19+IgM+ cells, 48.9 (42.8) vs. 112.5 (81.7) (K/μL), p < 0.0001. The ratio of early/late apoptotic B lymphocytes was reduced (16.8 (10.9) vs. 110 (25.4), p = 0.03). CD19+CD5+ cells were the only cell type with an increased proportion in ESRD-T0 patients (2.7 (3.7) vs. 0.6 (1.1), p < 0.0001). After 6 months on CAPD or HD, CD19+CD27−(%) and early apoptotic lymphocytes were reduced further. The HD patients also showed a significant increase in late apoptotic lymphocytes, from 1.2 (5.7) to 4.2 (7.2) K/mL, p = 0.02. Conclusions. B cells and most of their subtypes were significantly reduced in ESRD-T0 patients compared to controls, the only exception being CD19+CD5+ cells. Apoptotic changes were prominent in ESRD-T0 patients and were exacerbated by HD. Full article

Wastewater treatment, as a crucial component of the urban water environment, consists of several energy-consumptive stages, therefore efficiency and energy savings measures are essential to maintain them as environmentally sustainable and economically viable. Operational and technical data from WWTPs in Greece have been collected as well as a sample from 61 facilities with key energy profile components. Energy consumption was assessed by specific key performance indicators (KPIs); specific energy consumption expressed per population equivalent (from 3 to 150 kWh/PE), per cubic meter treated (from 0.2 to 2.0 kWh/m³) and per unit of organic load removed (from 0.03 to 7.13 kWh/COD_removed). Full article