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For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access. We did two single-arm phase 2 trials at six centres in the USA and Poland. We enrolled adults with end-stage renal disease. A novel bioengineered human acellular vessel was implanted into the arms of patients for haemodialysis access. Primary endpoints were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months. All patients were followed up for at least 1 year, or had a censoring event. These trials are registered with ClinicalTrials.gov, NCT01744418 and NCT01840956. Human acellular vessels were implanted into 60 patients. Mean follow-up was 16 months (SD 7·6). One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. At 6 months, 63% (95% CI 47–72) of patients had primary patency, 73% (57–81) had primary assisted patency, and 97% (85–98) had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% (17–40) had primary patency, 38% (26–51) had primary assisted patency, and 89% (74–93) had secondary patency. Bioengineered human acellular vessels seem to provide safe and functional haemodialysis access, and warrant further study in randomised controlled trials. Humacyte and US National Institutes of Health.

Calprotectin is a calcium-binding protein involved in inflammatory processes. In the context of abdominal aortic aneurysm (AAA), elevated levels of calprotectin may indicate immune system activation and chronic inflammation, which are among the mechanisms contributing to the development and progression of AAA. The receptor for advanced glycation end-products (RAGE) is a receptor that binds various ligands, including advanced glycation end-products formed during the glycation of proteins and lipids under oxidative stress conditions. Activation of RAGE is associated with inflammatory processes, oxidative stress, and tissue remodeling, which may contribute to the weakening of the aortic wall and aneurysm formation. The main objective of this study was to evaluate the effectiveness of both biomarkers in distinguishing patients with abdominal aortic aneurysm. A total of 27 patients with diagnosed AAA were included in the study. The control group consisted of 27 patients without AAA. Plasma levels of calprotectin and sRAGE were measured in both groups. Statistical analysis included the Shapiro–Wilk test, Mann–Whitney U test, and the Hosmer-Lemeshow (H-L) test. The likelihood of having AAA was found to be over one hundred times greater in individuals classified into the AAA group based on a decision tree model using calprotectin and sRAGE levels, compared to those classified into the no-AAA group. Calprotectin concentration was identified as a stronger predictor of AAA than sRAGE. The optimal cut-off value for plasma calprotectin was determined as ≥1136 ng/mL, yielding a sensitivity of 81.5% and a specificity of 100.0% for discriminating AAA patients from controls. It may be beneficial in future studies to explore non-invasive approaches, such as measuring calprotectin levels in stool and sRAGE in urine, as a potential screening method for AAA. Monitoring the concentrations of these biomarkers in bodily fluids, as a non-invasive method, could support screening efforts for AAA.

The changing environment and modified lifestyles have meant that many vitamins and minerals are deficient in a significant portion of the human population. Therefore, supplementation is a viable nutritional approach, which helps to maintain health and well-being. The supplementation efficiency of a highly hydrophobic compound such as cholecalciferol (logP > 7) depends predominantly on the formulation. To overcome difficulties associated with the evaluation of pharmacokinetics of cholecalciferol, a method based on the short time absorption data in the clinical study and physiologically based mathematical modeling is proposed. The method was used to compare pharmacokinetics of liposomal and oily formulations of vitamin D3. The liposomal formulation was more effective in elevating calcidiol concentration in serum. The determined AUC value for liposomal vitamin D3 formulation was four times bigger than that for the oily formulation.

Purpose Robotic colorectal surgery continues to rise in popularity, but there remains little evidence on the stress response following the procedure. The aim of this study was to evaluate the inflammatory response to robotic colorectal surgery and compare it with the response generated by open colorectal surgery. Methods This was a prospective nonrandomized comparative study involving 61 patients with colorectal cancer. The evaluation of inflammatory response to either robotic or open colorectal surgery was expressed as changes in interleukin-1β, interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor-α, C-reactive protein, and procalcitonin during the first three postoperative days. Results Of the 61 patients, 33 underwent robotic colorectal surgery while 28 had open colorectal surgery. Groups were comparable with respect to age, sex, BMI, cancer stage, and type of resection. The relative increase of interleukin-1 receptor antagonist at 8 h postoperative, compared to baseline, was higher in the open group ( P  = 0.006). The decrease of interleukin-1 receptor antagonist on postoperative days 1 and 3, compared to the maximum at 8 h, was more pronounced in the open group than in the robotic group ( P  = 0.008, P  = 0.006, respectively), and the relative increase of interleukin-6 at 8 h after incision was higher in the open group ( P  = 0.007). The relative increase of procalcitonin on postoperative days 1 and 3 was higher in the open group than the robotic group ( P  < 0.001, P  = 0.004, respectively). Conclusions This study shows that when compared with open colorectal surgery, robotic colorectal surgery results in a less pronounced inflammatory response and more pronounced anti-inflammatory action.

Minimally invasive surgery is known to lessen postoperative stress and complications compared with open procedures, yet its molecular effects on immunity and cancer-related mechanisms remain unclear. This study examined immune and inflammatory responses after robot-assisted (RS) versus open (OS) colorectal cancer surgery. Sixty-one patients (RS = 30; OS = 31) were enrolled. Blood samples were collected before surgery and at 8, 24, and 72 h post-incision. Cytokines, growth factors, and prostanoids were measured using multiplex immunoassays and mass spectrometry to assess systemic immune and inflammatory changes. Surgery type markedly influenced perioperative immune profiles. RS induced stronger activation of Th1-associated cytokines, including IFNγ and IP-10, suggesting enhanced cellular immune responsiveness. In contrast, Th2 cytokines and other immunosuppressive mediators—such as IL-4, IL-10, and G-CSF—showed smaller or transient increases after RS, whereas OS triggered broader and more sustained elevations. Angiogenic factors (VEGF-A, PDGF-BB, FGF2) rose significantly after OS but remained comparatively lower and returned to baseline faster after RS, indicating a weaker proangiogenic response. Similarly, postoperative surges in prostaglandins linked to inflammation and tumor progression (PGE2, PGF2α) were blunted and resolved earlier following RS. Overall, the robotic approach was associated with reduced inflammatory and immunosuppressive activity, faster recovery of immune balance, and diminished biochemical signals favoring angiogenesis and potential tumor regrowth, suggesting a potential protective effect against pathogens and cancer-promoting mechanisms after colorectal tumor resection.

Mitochondria, as multifunctional and partially independent structures, play a crucial role in determining essential life processes. Recently, their significance in reproductive biology has gained increasing attention. This review aims to comprehensively analyse the role of mitochondrial processes in oocyte maturation and embryo culture. A comprehensive literature review was conducted to highlight the importance of mitochondrial activity in the early stages of life formation. Proper mitochondrial function provides energy, maintains genomic stability, and ensures optimal conditions for fertilisation and embryo progression. Understanding these processes is essential to optimise culture conditions and identify new mitochondrial biomarkers that improve reproductive success and improve assisted reproductive technologies (ARTs). Enhancing mitochondrial function in female reproductive cells is the key to improving oocyte and embryo quality, which can lead to better in vitro fertilisation and embryo transfer. Furthermore, advances in diagnostic techniques, such as mitochondrial genome sequencing, offer a more precise understanding of the relationship between mitochondrial health and oocyte quality. However, fully understanding mitochondrial functions is only part of the challenge. Expanding knowledge of the interactions between mitochondria and other cellular structures is crucial for future advancements in reproductive medicine. Understanding these complex relationships will provide deeper insight into improving reproductive outcomes and embryo development.

Cancer-associated fibroblasts (CAFs) are well-known to be part of the tumor microenvironment. This heterogeneous population of cells of the tumor microenvironment via secretion of various growth factors and cytokines was shown to contribute to increased cancer cell proliferation rate, migration, invasiveness and other key processes such as angiogenesis and lymphangiogenesis. Recent studies identified podoplanin as a marker of CAFs in various malignancies and its expression in these cells was shown to influence cancer progression. In some studies it yielded a prognostic impact on patient survival which was strongly dependent on the entity of the tumor. This review summarizes recent findings concerning the biology of podoplanin in cancer progression with particular emphasis on its expression in CAFs.

HIV infection is associated with an increased risk of cardiovascular disease in connection with atherosclerosis and thromboembolic complications. The pathogenesis of atherosclerosis is still unclear in this group of patients. Studies on pathogenesis of atherosclerosis in the general population emphasize the role of the extrinsic pathway of blood coagulation, particularly the tissue factor (TF) and tissue factor pathway inhibitor (TFPI). The effect of persistent activation of the immune system on enhanced expression of TF on the surface of monocytes in subjects infected with HIV is known to be correlated with the level of HIV RNA in blood serum. The aim of this study was to evaluate the concentration of TF and its inhibitor TFPI in blood plasma, the impact of traditional and non-traditional cardiovascular risk factors on their concentration and the impact of both markers of haemostasis on the severity of subclinical atherosclerosis as assessed by the intima-media measurement of the carotid artery in HIV infected patients. The study included 121 HIV-infected people with known clinical, immunological and virological status. The control group consisted of 42 healthy individuals, selected in terms of age and sex. Higher concentrations of TF occurred in HIV-infected patients with a low current plasma HIV RNA level, nadir CD4+ T-cell count and longer duration of cumulative antiretroviral treatment. In multivariate analysis, it was the length of cumulative NRTI treatment that impacted on the concentration of TF. The determinants of cardiovascular disease (CVD) risk factors and inflammatory markers did not show any effect on the concentrations of TF. The TFPI level in HIV-infected patients was significantly higher than in the control group and was negatively correlated with the current level of HIV RNA and nadir CD4+ T-cell count, being higher in patients subjected to antiretroviral treatment. It was shown that the higher the cardiovascular risk and the higher the levels of total cholesterol, low-density lipoprotein cholesterol (LDL) and non-high-density lipoprotein cholesterol (non-HDL), the higher the concentrations of TFPI observed. The levels of TF and TFPI were positively correlated with carotid intima media thickness (cIMT); in the multivariate analysis, TF, non-HDL cholesterol and lifetime smoking (pack-years) independently affected the growth of cIMT. A similar effect on cIMT was demonstrated by TFPI.

The immune response and specific antibody production in COVID-19 are among the key factors that determine both prognostics for individual patients and the global perspective for controlling the pandemics. So called \"dark figure\", that is, a part of population that has been infected but not registered by the health care system, make it difficult to estimate herd immunity and to predict pandemic trajectories. Here we present a follow up study of population screening for hidden herd immunity to SARS-CoV-2 in individuals who had never been positively diagnosed against SARS-CoV-2; the first screening was in May 2021, and the follow up in December 2021. We found that specific antibodies targeting SARS-CoV-2 detected in May as the \"dark figure\" cannot be considered important 7 months later due to their significant drop. On the other hand, among participants who at the first screening were negative for anti-SARS-CoV-2 IgG, and who have never been diagnosed for SARS-CoV-2 infection nor vaccinated, 26% were found positive for anti-SARS-CoV-2 IgG. This can be attributed to of the \"dark figure\" of the recent, fourth wave of the pandemic that occurred in Poland shortly before the study in December. Participants who were vaccinated between May and December demonstrated however higher levels of antibodies, than those who undergone mild or asymptomatic (thus unregistered) infection. Only 7% of these vaccinated participants demonstrated antibodies that resulted from infection (anti-NCP). The highest levels of protection were observed in the group that had been infected with SARS-CoV-2 before May 2021 and also fully vaccinated between May and December. These observations demonstrate that the hidden fraction of herd immunity is considerable, however its potential to suppress the pandemics is limited, highlighting the key role of vaccinations.

Population immunity (herd immunity) to SARS-CoV-2 derives from two sources: vaccinations or cases of infection with the virus. Infections can be diagnosed as COVID-19 and registered, or they can be asymptomatic, oligosymptomatic, or even full-blown but undiagnosed and unregistered when patients recovered at home. Estimation of population immunity to SARS-CoV-2 is difficult and remains a subject of speculations. Here we present a population screening for SARS-CoV-2 specific IgG and IgA antibodies in Polish citizens (N = 501) who had never been positively diagnosed with or vaccinated against SARS-CoV-2. Serum samples were collected in Wrocław (Lower Silesia) on 15th and 22nd May 2021. Sera from hospitalized COVID-19 patients (N = 22) or from vaccinated citizens (N = 14) served as positive controls. Sera were tested with Microblot-Array COVID-19 IgG and IgA (quantitative) that contain specific SARS-CoV-2 antigens: NCP, RBD, Spike S2, E, ACE2, PLPro protein, and antigens for exclusion cross-reactivity with other coronaviruses: MERS-CoV, SARS-CoV, HCoV 229E Np, HCoV NL63 Np. Within the investigated population of healthy individuals who had never been positively diagnosed with or vaccinated against SARS-CoV-2, we found that 35.5% (178 out of 501) were positive for SARS-CoV-2-specific IgG and 52.3% (262 out of 501) were positive for SARS-CoV-2-specific IgA; 21.2% of the investigated population developed virus-specific IgG or IgA while being asymptomatic. Anti-RBD IgG, which represents virus-neutralizing potential, was found in 25.6% of individuals (128 out of 501). These patients, though positive for anti-SARS-CoV-2 antibodies, cannot be identified in the public health system as convalescents due to undiagnosed infections, and they are considered unaffected by SARS-CoV-2. Their contribution to population immunity against COVID-19 should however be considered in predictions and modeling of the COVID-19 pandemic. Of note, the majority of the investigated population still lacked anti-RBD IgG protection (74.4%); thus vaccination against COVID-19 is still of the most importance for controlling the pandemic.