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A double primary colorectal cancer (CRC) in a familial setting signals a high risk of CRC. In order to identify novel CRC susceptibility genes, we whole-exome sequenced germline DNA from nine persons with a double primary CRC and a family history of CRC. The detected variants were processed by bioinformatics filtering and prioritization, including STRING protein-protein interaction and pathway analysis. A total of 150 missense, 19 stop-gain, 22 frameshift and 13 canonical splice site variants fulfilled our filtering criteria. The STRING analysis identified 20 DNA repair/cell cycle proteins as the main cluster, related to genes CHEK2, EXO1, FAAP24, FANCI, MCPH1, POLL, PRC1, RECQL, RECQL5, RRM2, SHCBP1, SMC2, XRCC1, in addition to CDK18, ENDOV, ZW10 and the known mismatch repair genes. Another STRING network included extracellular matrix genes and TGFβ signaling genes. In the nine whole-exome sequenced patients, eight harbored at least two candidate DNA repair/cell cycle/TGFβ signaling gene variants. The number of families is too small to provide evidence for individual variants but, considering the known role of DNA repair/cell cycle genes in CRC, the clustering of multiple deleterious variants in the present families suggests that these, perhaps jointly, contributed to CRC development in these families.
- MeSH
- dospělí MeSH
- genetická predispozice k nemoci * MeSH
- kolorektální nádory * genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- oprava DNA genetika MeSH
- rodokmen MeSH
- sekvenování exomu * metody MeSH
- senioři MeSH
- zárodečné mutace * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: STereotactic Arrhythmia Radioablation (STAR) showed promising results in patients with refractory ventricular tachycardia. However, clinical data are scarce and heterogeneous. The STOPSTORM.eu consortium was established to investigate and harmonize STAR in Europe. The primary goal of this benchmark study was to investigate current treatment planning practice within the STOPSTORM project as a baseline for future harmonization. METHODS AND MATERIALS: Planning target volumes (PTVs) overlapping extracardiac organs-at-risk and/or cardiac substructures were generated for 3 STAR cases. Participating centers were asked to create single-fraction treatment plans with 25 Gy dose prescriptions based on in-house clinical practice. All treatment plans were reviewed by an expert panel and quantitative crowd knowledge-based analysis was performed with independent software using descriptive statistics for International Commission on Radiation Units and Measurements report 91 relevant parameters and crowd dose-volume histograms. Thereafter, treatment planning consensus statements were established using a dual-stage voting process. RESULTS: Twenty centers submitted 67 treatment plans for this study. In most plans (75%) intensity modulated arc therapy with 6 MV flattening filter free beams was used. Dose prescription was mainly based on PTV D95% (49%) or D96%-100% (19%). Many participants preferred to spare close extracardiac organs-at-risk (75%) and cardiac substructures (50%) by PTV coverage reduction. PTV D0.035cm3 ranged from 25.5 to 34.6 Gy, demonstrating a large variety of dose inhomogeneity. Estimated treatment times without motion compensation or setup ranged from 2 to 80 minutes. For the consensus statements, a strong agreement was reached for beam technique planning, dose calculation, prescription methods, and trade-offs between target and extracardiac critical structures. No agreement was reached on cardiac substructure dose limitations and on desired dose inhomogeneity in the target. CONCLUSIONS: This STOPSTORM multicenter treatment planning benchmark study not only showed strong agreement on several aspects of STAR treatment planning, but also revealed disagreement on others. To standardize and harmonize STAR in the future, consensus statements were established; however, clinical data are urgently needed for actionable guidelines for treatment planning.
- MeSH
- benchmarking * MeSH
- celková dávka radioterapie MeSH
- komorová tachykardie chirurgie radioterapie MeSH
- konsensus * MeSH
- kritické orgány * účinky záření MeSH
- lidé MeSH
- plánování radioterapie pomocí počítače * normy metody MeSH
- radiochirurgie * normy metody MeSH
- radioterapie s modulovanou intenzitou metody normy MeSH
- srdce účinky záření MeSH
- srdeční arytmie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa MeSH
PURPOSE: This study aimed to compare the image quality of the Siemens Biograph mCT40 (photomultiplier-based system - PMT) and the Siemens Vision600 (silicon photomultiplier-based system - SiPM) using a modified NEMA IEC Body phantom (Data Spectrum). METHODS: SiPM-based Vision600 has a smaller crystal size (3.2 × 3.2 mm vs. 4.0 × 4.0 mm in the PMT-based mCT40), resulting in better spatial resolution. Enhanced time-of-flight (TOF) timing and higher sensitivity leads to nearly four times higher effective sensitivity. The standard NEMA IEC Body phantom was modified with a 3D-printed holder to accommodate also Hollow and Micro Hollow Spheres of 15.4 mm, 12.4 mm, 7.9 mm, 6.2 mm, 5.0 mm, and 4.0 mm. Each of the three acquisition sessions per scanner included 18 time points and spanned 5.6 half-lives to assess system performance at varying activity concentrations in the field of view. RESULTS: Recovery curves for both systems were similar when identical post-reconstruction filters were applied. The SiPM-based Vision600 system detected smaller sources at significantly lower activity concentrations, and the variations in standardized uptake value (SUVmax, SUVA50) measurements were generally smaller compared to those of the PMT-based system. The two smallest sources became undetectable below 63 MBq and 16 MBq on the PMT system, versus 20 MBq and 6.5 MBq on the SiPM system. CONCLUSIONS: SiPM technology demonstrated superior performance compared to PMT in detecting small sources in low-activity scenarios and provided more robust quantification results. It is recommended to use averaged SUV metrics, such as SUVA50 or SUVpeak.
Fragile X syndrome (FXS) is a neurodevelopmental disorder oftentimes associated with abnormal social behaviors and altered sensory responsiveness. It is hypothesized that the inappropriate filtering of sensory stimuli, including olfaction, can lead to aberrant social behavior in FXS. However, previous studies investigating olfaction in animal models of FXS have shown inconsistent results. Here, we found that Fmr1 knock-out (KO) mice, a mouse model of FXS, showed increased sniffing duration for non-social odors during their first exposure. Additionally, while wild-type (WT) males demonstrated differences in behavioral patterns between non-social odors while Fmr1 KO males did not show such distinction. We also showed that Fmr1 KO males spent significantly less time sniffing female urine odor compared to WT males. Moreover, we found an increased volume of the olfactory bulb in Fmr1 KO males. Overall, our findings suggest that the Fmr1 KO mice demonstrate atypical olfactory behaviors as well as structural changes in the olfactory bulb.
- MeSH
- bulbus olfactorius * metabolismus MeSH
- chování zvířat MeSH
- čich * fyziologie MeSH
- modely nemocí na zvířatech MeSH
- myši knockoutované * MeSH
- myši MeSH
- odoranty * MeSH
- protein FMRP * genetika metabolismus MeSH
- syndrom fragilního X * patofyziologie genetika MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: Electrical stimulation involving temporal interference of two different kHz frequency sinusoidal electric fields (temporal interference (TI)) enables non-invasive deep brain stimulation, by creating an electric field that is amplitude modulated at the slow difference frequency (within the neural range), at the target brain region. OBJECTIVE: Here, we investigate temporal interference neural stimulation using square, rather than sinusoidal, electric fields that create an electric field that is pulse-width, but not amplitude, modulated at the difference frequency (pulse-width modulated temporal interference, (PWM-TI)). METHODS/RESULTS: We show, using ex-vivo single-cell recordings and in-vivo calcium imaging, that PWM-TI effectively stimulates neural activity at the difference frequency at a similar efficiency to traditional TI. We then demonstrate, using computational modelling, that the PWM stimulation waveform induces amplitude-modulated membrane potential depolarization due to the membrane's intrinsic low-pass filtering property. CONCLUSIONS: PWM-TI can effectively drive neural activity at the difference frequency. The PWM-TI mechanism involves converting an envelope amplitude-fixed PWM field to an amplitude-modulated membrane potential via the low-pass filtering of the passive neural membrane. Unveiling the biophysics underpinning the neural response to complex electric fields may facilitate the development of new brain stimulation strategies with improved precision and efficiency.
- MeSH
- elektrická stimulace MeSH
- mozek * MeSH
- počítačová simulace MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Článek popisuje případ neúmyslného intravenózního podání prokain-penicilinu (P-PNC) místo ordinovaného krystalického penicilinu (G-PNC), přičemž tento výjimečný incident je analyzován z pohledu lidského faktoru a řízení kvality pomocí metody kořenové analýzy (Root Cause Analysis, RCA). Případ zdůrazňuje zásadní roli infuzního setu s filtrem, který zamezil průchodu větších částic suspenze do krevního oběhu pacienta a tím předešel vážnějším následkům. Incident je současně významným příkladem pro ošetřovatelskou praxi, který podtrhuje důležitost důsledného dodržování bezpečnostních a standardních operačních postupů (SOP) v rámci kompetencí sester a nutnost zapojení klinického farmaceuta při práci s LASA léčivy.
The article describes a case of unintended intravenous administration of procaine penicillin (P-PNC) instead of the prescribed crystalline penicillin (G-PNC). This unique incident is analyzed from the perspectives of human factors and quality management, using the Root Cause Analysis (RCA) method. A key element was the protective role of the infusion set with a filter, which prevented larger suspension particles from entering the patient's bloodstream, thereby averting more serious consequences. This case also serves as an important example for nursing practice, emphasizing the necessity of adhering to safety and Standard Operating Procedures (SOP) within the scope of nursing competencies, as well as the crucial role of clinical pharmacists in managing LASA (Look-Alike, Sound-Alike) medications.
- Klíčová slova
- kořenová analýza, Hoigné syndrom,
- MeSH
- intravenózní podání MeSH
- lidé MeSH
- medikační omyly * MeSH
- odborná způsobilost MeSH
- prokain penicilin G aplikace a dávkování škodlivé účinky MeSH
- řízení kvality MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The level of the human body's burden of benzophenone and camphor ultraviolet (UV) filters can be estimated from their urinary levels. The present study describes the implementations and validation of the sensitive analytical method for the analysis of seven benzophenone and two camphor UV filters in urine. Sample preparation includes overnight enzymatic hydrolysis and ethyl acetate extraction followed by purification by dispersive solid-phase extraction using a sorbent Z-Sep. For the analysis, ultra-high performance liquid chromatography coupled with tandem mass spectrometry was used. Validation was performed using a Standard Reference Material® 3673 and an artificially contaminated urine sample. Target analyte recoveries ranged from 79-113% with repeatability expressed as a relative standard deviation of 2-15%. The limits of quantification were between 0.001 and 0.100 ng/mL in urine. This method was subsequently applied to examine the urine samples collected from Czech women. The analytes benzophenone-1 and 4-hydroxy-benzophenone were the most common analytes present in 100% of the samples, whereas benzophenone-3 was quantified in only 90% of the urine samples. The other four determined benzophenone derivatives were quantified in ≤33% of the samples. The derivatives of camphor were not detected in any samples. This method could be applied in biomonitoring studies.
- Publikační typ
- časopisecké články MeSH
Aims: The purpose of this study is to evaluate an Altmetric analysis of the 50 most cited refractive surgery articles in Ophthalmology journals and to compare them with traditional metrics. Methods: The term "refractive surgery" was searched, using a time filter between 2010-2020 in the Web of Science core collection database. The 50 most cited articles between 2010 and 2020 were recorded. Descriptive statistics were performed. The Spearman correlation test was used to evaluate the correlation between traditional metrics and Altmetrics. Results: The Altmetric scores of the top 50 articles ranged from 0 to 25, and the median Altmetric score was 4. The citation numbers of the 50 articles ranged from 83 to 523, and the median citation number was 119.5. The most cited article topic was "Toric Intraocular Lens"; the topics with the highest Altmetric scores were "Toric Intraocular Lens" and "Trifocal Intraocular Lens". There was no significant correlation between Altmetric scores and number of citations. There was a weak correlation between Altmetric scores and the average citation per year. Conclusion: The Altmetric score is insufficient, compared with traditional metrics, to show the scientific value of articles on refractive surgery. Altmetrics can be used to supplement traditional metrics.
Distance-based detection (DbD) on paper-based microfluidic analytical devices (μPADs) has emerged as a promising, cost-effective, simple, and instrumentation-free assay method. Broadening the applicability of a new way of immobilization of reagent for DbD on μPADs (DμPADs) is presented, employing an ion exchange (IE) interaction of an anionic metallochromic reagent, 2-(5-bromo-2-pyridylazo)-5-[N-n-propyl-N-(3-sulfopropyl)amino]phenol (5-Br-PAPS), on the anion-exchange filter paper. The IE DμPADs demonstrate superiority over standard cellulose filter paper in terms of the degree of reagent immobilization, detection sensitivity, and clear detection endpoints due to the strong retention of 5-Br-PAPS. The study investigated various parameters influencing DbD, including 5-Br-PAPS concentrations (0.25-1 mM), buffer types (acetic acid-Tris, MES), buffer concentrations (20-500 mM), and auxiliary complexing agents (acetic, formic, and glycolic acids). Subsequently, the performance of 17 metals (Ag+, Cd2+, Co2+, Cr3+, Cu2+, Fe2+, Hg2+, La2+, Mn2+, Ni2+, Pb2+, Ti2+, Zn2+, Al3+, As3+, Fe3+, and V4+) was evaluated, with color formation observed for 12 metals. Additionally, the paper surface was examined using SEM and SEM-EDX to verify the suitability of certain areas in the detection channel for reagent immobilization and metal binding. This method demonstrates quantitation limits of metals in the low μg mL-1 range, showing great potential for the rapid screening of toxic metals commonly found in herbal supplements and cosmetics regulated by the Food and Drug Administration (FDA). Thus, it holds promise for enhancing safety and regulatory compliance in product quality assessment. Furthermore, this method offers a cost-effective, environmentally sustainable, and user-friendly approach for the rapid visual quantification of heavy metals for in-field analysis, eliminating the need for complex instrumentation.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: This study aims to review the existing knowledge on the cost-effectiveness and item costs related to the diagnosis and treatment of gastroesophageal reflux disease (GERD) patients at different stages. METHODS: The study adhered to the PRISMA guidelines. The systematic search involved several steps: finding and identifying relevant articles, filtering them according to the set criteria, and examining the final number of selected articles to obtain the primary information. The number of articles published between 2013 and September 2024 in the Web of Science and PubMed databases was considered. The CHEERS checklist was used for the risk of bias assessment. Ultimately, 36 studies were included. RESULTS: Regarding the cost-effectiveness of GERD treatment, Proton pump inhibitors (PPIs) appeared to be the dominant solution for non-refractory patients. However, this might change with the adoption of the novel drug vonoprazan, which is more effective and cheaper. With advancements in emerging technologies, new diagnostic and screening approaches such as Endosheath, Cytosponge, and combined multichannel intraluminal impedance and pH monitoring catheters should be considered, with potential implications for optimal GERD management strategies. DISCUSSION: The new diagnostic methods are reliable, safe, and more comfortable than standard procedures. PPIs are commonly used as the first line of treatment for GERD. Surgery, such as magnetic sphincter augmentation or laparoscopic fundoplication, is only recommended for patients with treatment-resistant GERD or severe symptoms. OTHER: Advances in emerging technologies for diagnostics and screening may lead to a shift in the entire GERD treatment model, offering less invasive options and potentially improving patients' quality of life.
- MeSH
- analýza nákladů a výnosů * MeSH
- gastroezofageální reflux * diagnóza terapie ekonomika farmakoterapie MeSH
- inhibitory protonové pumpy * terapeutické užití ekonomika MeSH
- lidé MeSH
- osobní újma zaviněná nemocí MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
