Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. To examine this question, we studied genome-wide microarray results from 5086 kidney transplant biopsies (from 4170 patients). An updated molecular archetypal analysis designated 56% of biopsies as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower estimated glomerular filtration rate, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR, respectively, diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems.

• MeSH
• biopsie MeSH
• dospělí MeSH
• hodnoty glomerulární filtrace MeSH
• isoprotilátky imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• přežívání štěpu imunologie   MeSH
• prognóza MeSH
• rejekce štěpu * patologie   imunologie   etiologie   MeSH
• rizikové faktory MeSH
• T-lymfocyty imunologie   MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• vyšetření funkce ledvin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The role of primary healthcare (PHC) during a pandemic varies across European countries. The coronavirus disease 2019 (COVID-19) pandemic has altered the working practices of family medicine doctors and impacted the resilience of healthcare systems. OBJECTIVES: This study aimed to examine European healthcare system responses to the pandemic, focusing on rural and urban differences. MATERIAL AND METHODS: This cross-sectional, mixed-methods study used a semi-structured online questionnaire with 68 questions, including 21 free-text comments. Data were collected from May 2020 to January 2021. Key informants from 16 European Rural and Isolated Practitioners Association (EURIPA) member countries distributed questionnaires to 406 PHC doctors. Data were analyzed using descriptive statistics and nonparametric tests (χ2, Kruskal-Wallis, Mann-Whitney U) with a significance threshold of 0.05. RESULTS: A statistically significant difference was found between rural (36.4%, 55/151), semirural (19.4%, 24/124) and urban populations (29.8%, 39/131) regarding medicine shortages (χ2 = 9.91, degrees of freedom (df) = 4, p = 0.042). The semirural setting showed a statistically significant difference from the other settings (p = 0.004 in post hoc χ2 test). Significant differences were found between countries in resilience features including, effectiveness of triage, adapting to the rapidly changing requirements, government help, existence of a community resilience group, improved interprofessional collaboration, medicine shortage, and general practitioners (GPs) involvement in palliative care. CONCLUSIONS: Medicine shortage was more prevalent in rural and urban areas compared to semirural areas. Differences were observed between countries in their responses to the pandemic, particularly in adapting to the rapidly changing requirements, effectiveness of triage, government help, and the existence of a community resilience group. These differences were confirmed with qualitative analysis. The results emphasize the need for tailored approaches considering diverse contexts in shaping effective healthcare system resilience.

• MeSH
• COVID-19 * epidemiologie   MeSH
• lidé MeSH
• pandemie MeSH
• primární zdravotní péče * organizace a řízení   MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• SARS-CoV-2 MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

PURPOSE: We aimed to find predictive tumour characteristics as detected by interim positron-emission tomography/magnetic resonance imaging (PET/MRI) in cervical cancer patients. We also investigated the type of interim response. Furthermore, we compared the investigated parameters with disease-free (DFS) and overall survival (OS) outcomes. METHODS: We evaluated 108 patients treated between August 2015 and January 2023 with external-beam radiotherapy (EBRT) and image-guided adaptive brachytherapy (IGABT) who had undergone pretreatment staging, subsequent mid-treatment evaluation after completed EBRT and definitive restaging 3 months after completing the whole treatment using PET/MRI. Patients were then divided into two groups based on the RECIST and PERCIST criteria: responders (achieving complete metabolic response, CMR) and non-responders (non-CMR). These two groups were compared using selected parameters obtained at pre-PET/MRI and mid-PET/MRI. The early response to treatment as evaluated by mid-PET/MRI was categorized into three types: interim complete metabolic response, interim nodal response and interim nodal persistence. RESULTS: Mid-TLG‐S (the sum of total lesion glycolysis for the primary tumour plus pelvic and para-aortic lymph nodes) parameter showed the best discriminatory ability for predicting non-CMR. The second factor with significant discriminatory ability was mid-MTV‐S (the sum of the metabolic tumour volume of the primary tumour plus pelvic and para-aortic lymph nodes). The strongest factor, mid-TLG‐S, showed a sensitivity of 40% and a specificity of 90% at a threshold value of 70. We found a statistically significant association of DFS and OS with the following parameters: number of chemotherapy cycles, early response type and CMR vs. non-CMR. CONCLUSION: We were able to identify thresholds for selected parameters that can be used to identify patients who are more likely to have worse DFS and OS. The type of early response during concurrent chemoradiotherapy (CCRT) was also significantly associated with DFS and OS. These aspects represent an important contribution to the possible stratification of patients for subsequent individualised adjuvant treatment.

• MeSH
• brachyterapie MeSH
• chemoradioterapie * metody   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• multimodální zobrazování * MeSH
• nádory děložního čípku * terapie   diagnostické zobrazování   patologie   mortalita   MeSH
• pozitronová emisní tomografie * MeSH
• přežití bez známek nemoci MeSH
• radioterapie řízená obrazem MeSH
• senioři MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Large vessel carotid stenosis is a significant cause of ischaemic stroke. Indications for surgical revascularisation depend on the severity of the stenosis and clinical symptoms. However, mild symptoms such as TIA (Transient ischaemic attack), amaurosis fugax or minor stroke precede large strokes in only 15% of cases. AIM: The aim of this prospective study is to evaluate whether retinal perfusion is impacted in significant carotid stenosis. Automated retinal oximetry will be used to better assess perfusion in the post-stenotic basin. We presume the more stenotic the blood vessel, the more reduced the retinal perfusion is, resulting in adaptive changes such as greater arteriovenous saturation difference due to greater oxygen extraction. This could broaden the indication spectrum for revascularisation for carotid stenosis. METHODS: We plan to enroll yearly 50 patients with significant carotid stenosis and cross-examine them with retinal oximetry. The study group will provide stenotic vessels and, non-stenotic vessels will form the control group. Patients with significant carotid stenosis will undergo an MRI (Magnetic Resonnance imaging) examination to determine the presence of asymptomatic recent ischaemic lesions in the stenotic basin, and the correlation to oximetry parameters. STATISTICS: The stenosis severity and retinal oximetry parameters will be compared for study and control groups with a threshold of 70%, respectively 80% and 90% stenosis. Results will be then reevaluated with emphasis on MRI findings in the carotid basin. CONCLUSION: This prospective case control study protocol will be used to launch a multicentre trial assessing the relationship between significant carotid stenosis and retinal perfusion measured with automated retinal oximetry. Despite these differences, the findings indicate the potential of retinal oximetry for noninvasive real-time measurements of oxyhaemoglobin saturation in central nervous system vessels. Following calibration upgrade and technological improvement, verification retinal oximetry may potentially be applied to critically ill and anaesthesia care patients. The study on combined scanning laser ophthalmoscope and retinal oximetry supports the feasibility of the technique for oximetry analysis in newly born babies. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT06085612.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• oxymetrie * metody   MeSH
• prospektivní studie MeSH
• retina diagnostické zobrazování   patofyziologie   MeSH
• retinální cévy diagnostické zobrazování   patofyziologie   MeSH
• senioři MeSH
• stenóza arteria carotis * patofyziologie   chirurgie   komplikace   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

This study presents a graphene field-effect transistor (gFET) biosensor with dual detection capabilities for SARS-CoV-2: one RNA detection assay to confirm viral positivity and the other for nucleocapsid (N-)protein detection as a proxy for infectiousness of the patient. This technology can be rapidly adapted to emerging infectious diseases, making an essential tool to contain future pandemics. To detect viral RNA, the highly conserved E-gene of the virus was targeted, allowing for the determination of SARS-CoV-2 presence or absence using nasopharyngeal swab samples. For N-protein detection, specific antibodies were used. Tested on 213 clinical nasopharyngeal samples, the gFET biosensor showed good correlation with RT-PCR cycle threshold values, proving its high sensitivity in detecting SARS-CoV-2 RNA. Specificity was confirmed using 21 pre-pandemic samples positive for other respiratory viruses. The gFET biosensor had a limit of detection (LOD) for N-protein of 0.9 pM, establishing a foundation for the development of a sensitive tool for monitoring active viral infection. Results of gFET based N-protein detection corresponded to the results of virus culture in all 16 available clinical samples and thus it also proved its capability to serve as a proxy for infectivity. Overall, these findings support the potential of the gFET biosensor as a point-of-care device for rapid diagnosis of SARS-CoV-2 infection and indirect assessment of infectiousness in patients, providing additional information for clinical and public health decision-making.

• MeSH
• biosenzitivní techniky * přístrojové vybavení   metody   MeSH
• COVID-19 * diagnóza   virologie   MeSH
• design vybavení MeSH
• elektronické tranzistory MeSH
• fosfoproteiny MeSH
• grafit * chemie   MeSH
• koronavirové nukleokapsidové proteiny izolace a purifikace   MeSH
• lidé MeSH
• limita detekce MeSH
• nazofarynx virologie   MeSH
• RNA virová * izolace a purifikace   analýza   MeSH
• SARS-CoV-2 * izolace a purifikace   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: This study aims to assess the suitability of Fitbit devices for real-time physical activity (PA) and sedentary behaviour (SB) monitoring in the context of just-in-time adaptive interventions (JITAIs) and event-based ecological momentary assessment (EMA) studies. METHODS: Thirty-seven adults (18-65 years) and 32 older adults (65+) from Belgium and the Czech Republic wore four devices simultaneously for 3 days: two Fitbit models on the wrist, an ActiGraph GT3X+ at the hip and an ActivPAL at the thigh. Accuracy measures included mean (absolute) error and mean (absolute) percentage error. Concurrent validity was assessed using Lin's concordance correlation coefficient and Bland-Altman analyses. Fitbit's sensitivity and specificity for detecting stepping events across different thresholds and durations were calculated compared to ActiGraph, while ROC curve analyses identified optimal Fitbit thresholds for detecting sedentary events according to ActivPAL. RESULTS: Fitbits demonstrated validity in measuring steps on a short time scale compared to ActiGraph. Except for stepping above 120 steps/min in older adults, both Fitbit models detected stepping bouts in adults and older adults with sensitivities and specificities exceeding 87% and 97%, respectively. Optimal cut-off values for identifying prolonged sitting bouts achieved sensitivities and specificities greater than 93% and 89%, respectively. CONCLUSIONS: This study provides practical insights into using Fitbit devices in JITAIs and event-based EMA studies among adults and older adults. Fitbits' reasonable accuracy in detecting short bouts of stepping and SB makes them suitable for triggering JITAI prompts or EMA questionnaires following a PA or SB event of interest.

• Publikační typ
• časopisecké články MeSH

PURPOSE: Utility of prostate-specific antigen density (PSAd) for risk-stratification to avoid unnecessary biopsy remains unclear due to the lack of standardization of prostate volume estimation. We evaluated the impact of ellipsoidal formula using multiparametric magnetic resonance (MRI) and semi-automated segmentation using tridimensional ultrasound (3D-US) on prostate volume and PSAd estimations as well as the distribution of patients in a risk-adapted table of clinically significant prostate cancer (csPCa). METHODS: In a prospectively maintained database of 4841 patients who underwent MRI-targeted and systematic biopsies, 971 met inclusions criteria. Correlation of volume estimation was assessed by Kendall's correlation coefficient and graphically represented by scatter and Bland-Altman plots. Distribution of csPCa was presented using the Schoots risk-adapted table based on PSAd and PI-RADS score. The model was evaluated using discrimination, calibration plots and decision curve analysis (DCA). RESULTS: Median prostate volume estimation using 3D-US was higher compared to MRI (49cc[IQR 37-68] vs 47cc[IQR 35-66], p < 0.001). Significant correlation between imaging modalities was observed (τ = 0.73[CI 0.7-0.75], p < 0.001). Bland-Altman plot emphasizes the differences in prostate volume estimation. Using the Schoots risk-adapted table, a high risk of csPCa was observed in PI-RADS 2 combined with high PSAd, and in all PI-RADS 4-5. The risk of csPCa was proportional to the PSAd for PI-RADS 3 patients. Good accuracy (AUC of 0.69 and 0.68 using 3D-US and MRI, respectively), adequate calibration and a higher net benefit when using 3D-US for probability thresholds above 25% on DCA. CONCLUSIONS: Prostate volume estimation with semi-automated segmentation using 3D-US should be preferred to the ellipsoidal formula (MRI) when evaluating PSAd and the risk of csPCa.

• MeSH
• hodnocení rizik MeSH
• klinické rozhodování MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• multiparametrická magnetická rezonance MeSH
• nádory prostaty * patologie   diagnostické zobrazování   MeSH
• prospektivní studie MeSH
• prostata * patologie   diagnostické zobrazování   MeSH
• prostatický specifický antigen * krev   MeSH
• senioři MeSH
• ultrazvukem navigovaná biopsie metody   MeSH
• velikost orgánu MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

Mitochondria (mt) represent the vital hub of the molecular physiology of the cell, being decision-makers in cell life/death and information signaling, including major redox regulations and redox signaling. Now we review recent advances in understanding mitochondrial redox homeostasis, including superoxide sources and H2O2 consumers, i.e., antioxidant mechanisms, as well as exemplar situations of physiological redox signaling, including the intramitochondrial one and mt-to-cytosol redox signals, which may be classified as acute and long-term signals. This review exemplifies the acute redox signals in hypoxic cell adaptation and upon insulin secretion in pancreatic beta-cells. We also show how metabolic changes under these circumstances are linked to mitochondrial cristae narrowing at higher intensity of ATP synthesis. Also, we will discuss major redox buffers, namely the peroxiredoxin system, which may also promote redox signaling. We will point out that pathological thresholds exist, specific for each cell type, above which the superoxide sources exceed regular antioxidant capacity and the concomitant harmful processes of oxidative stress subsequently initiate etiology of numerous diseases. The redox signaling may be impaired when sunk in such excessive pro-oxidative state.

• MeSH
• antioxidancia metabolismus   MeSH
• beta-buňky metabolismus   MeSH
• lidé MeSH
• mitochondrie * metabolismus   MeSH
• oxidace-redukce * MeSH
• oxidační stres fyziologie   MeSH
• signální transdukce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• biologie MeSH
• lékařská genetika MeSH
• molekulární medicína MeSH

• Konspekt
• Lékařské vědy. Lékařství
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• biologie
• NLK Publikační typ
• učebnice vysokých škol

PURPOSE: The aim of this study was to compare changes in the conventionally undiagnosed distal nasal visual field with RNFL in patients with early primary open-angle glaucoma (POAG). MATERIAL AND METHODS: 59 eyes of 32 patients (18 women, 14 men) with early stage POAG were included. All eyes were found to have a normal visual field (fast threshold program of 50 degrees nasally and 22 degrees temporally) with the Medmont M700. Visual acuity was 1.0 (with a possible correction ±3 D), and they had no other ocular pathology except glaucoma. The visual field was subsequently examined with the same instrument by moving the fixation point 40 degrees temporally (spatially adaptive program) and simultaneously turning the head 10 degrees nasally. A total of 89 examination points were included using flicker stimuli in a range of 0-120 degrees nasally. Nerve fiber layer (RNFL) and vessel density (VD) was measured using the in-built software of the Avanti RTVue XR instrument. Using Pearson's correlation coefficient, the results of visual field examination with RNFL without and after correction (by subtracting VD from total RNFL value) in the superior-nasal (SN-5) and inferior-nasal (IN-8) segments were compared. RESULTS: In all eyes, changes were found in the distal periphery of the nasal part of the visual field. No correlation was noted by comparison with RNFL. After adjusting RNFL for VD, we observed no correlation in the SN segment (5) (r=-0.03) and a very weak correlation in the IN segment (8) (r=-0.16). CONCLUSION: With a normal visual field tested by the rapid threshold glaucoma program, changes in the distal part of the nasal periphery of the visual field were found in the entire cohort and did not correlate with the RNFL and RNFL results after correction from VD.

• Publikační typ
• časopisecké články MeSH