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
- Adult MeSH
- Genetic Predisposition to Disease * MeSH
- Colorectal Neoplasms * genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- DNA Repair genetics MeSH
- Pedigree MeSH
- Exome Sequencing * methods MeSH
- Aged MeSH
- Germ-Line Mutation * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article 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
- Radiotherapy Dosage MeSH
- Tachycardia, Ventricular surgery radiotherapy MeSH
- Consensus * MeSH
- Organs at Risk * radiation effects MeSH
- Humans MeSH
- Radiotherapy Planning, Computer-Assisted * standards methods MeSH
- Radiosurgery * standards methods MeSH
- Radiotherapy, Intensity-Modulated methods standards MeSH
- Heart radiation effects MeSH
- Arrhythmias, Cardiac MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Europe MeSH
Cíl: Používání filtroventrilačních systémů v městských autobusech ve vyspělých zemích zvyšuje komfort a kvalitu vnitřního ovzduší v prostředcích pozemní dopravy. Mikrobiální kontaminace byla studována na výstupních a vstupních plochách 5 vzduchových filtrů vyjmutých z klimatizačního systému městských autobusů při pravidelné údržbě. Materiál a metodika: K získání vzorků z výstupní i vstupní strany filtrů byla použita technika suchého stěru. Kultivace byla provedena na různých selektivních nebo selektivně-diagnostických půdách pro kultivaci životaschopných bakterií. K identifikaci bakteriálních druhů bylo použito barvení podle Grama a imerzní mikroskopie. Vybrané kolonie byly rovněž podrobeny proteomické studii. Po identifikaci byly bakterie kvantifikovány. Výsledky: Na vstupním i výstupním povrchu filtrů převažovaly bakterie rodu Bacillus – Bacillus cereus, Bacillus subtilis, Bacillus licheniformis, Bacillus pumilus, Bacillus flexus. Identifikovány byli také bakterie rodů Staphylococcus, Brevibacillus, Peribacillus a Paenibacillus. Kvantifikace ukázala nízkou kontaminaci výstupních povrchů filtrů 1 a 2. Kontaminace vstupní a výstupní strany filtrů 3, 4 a 5 a odhalila téměř stejnou kontaminaci vstupních a výstupních ploch. Závěry: Podle nalezených výsledků doporučujeme buď častější výměnu filtrů, nebo volbu filtrů s nižší porozitou.
The use of HVAC in urban buses in developed countries increases the comfort and indoor air quality in the means of ground transportation. The microbial contamination was studied on outlet and inlet surfaces of 5 air filters removed from the urban buses HVAC during regular maintenance. To acquire samples from both the outlet and the inlet sides of the filters, dry swabbing technique was used. Cultivation was performed on different selective or selective-diagnostic agars, to cultivate viable bacteria. To identify the bacterial species, Gram stain and immerse microscopy was used. Selected colonies underwent the proteomic study (MALDI-TOF) as well. After identification, bacteria were quantified. The bacteria of the genus Bacillus – Bacillus cereus, Bacillus subtilis, Bacillus licheniformis, Bacillus pumilus, Bacillus flexus prevailed on both inlet and outlet surfaces of the filters. The members of genera Staphylococcus, Brevibacillus, Peribacillus or Paenibacillus were also identified. The quantification of colony forming units showed low contamination of the outlet surfaces of filters 1 and 2. The contamination of inlet and outlet sides of filters 3, 4, and 5 was comparable, revealed nearly the same contamination of inlet and outlet surfaces. In the case of filters 3, 4 and 5 we recommend more frequent filter changing or more efficient filter choice.
S rozvojem intenzivní medicíny u pediatrických pacientů s vrozenými i získanými protrombotickými stavy a léčbou onkologických a hematologických onemocnění přibývají v této skupině tromboembolické komplikace, které vedou za určitých anatomických a klinických podmínek ke zvážení implantace kaválních filtrů. Vzhledem k absenci indikačních kritérií a doporučených postupů pro použití kaválních filtrů u pediatrických pacientů je možné vycházet z doporučení platných pro dospělé. Tento přístup však vyžaduje vysokou míru individualizace a pečlivé sledování již zavedených kaválních filtrů.
With advancements in intensive care medicine for pediatric patients with congenital and acquired prothrombotic conditions, as well as those undergoing treatment for oncological and hematological disorders, the incidence of thromboembolic complications in this population has risen. Under specific anatomical and clinical conditions, caval filter implantation is increasingly considered a therapeutic option. In the absence of established indication criteria and guidelines for pediatric patients, current practices are largely extrapolated from adult recommendations. However, this approach necessitates a highly individualized decision-making process and meticulous long-term monitoring of implanted caval filters to optimize patient outcomes and minimize potential complications.
Neurodegenerative motor disorders affect the neuromuscular system challenging daily life and normal activity. Parkinson's Disease (PD) is among the most prevalent ones, with a large impact and rising prevalence rates. Speech is most affected by PD as far as phonatory and articulatory performance is concerned. Neuromotor activity (NMA) alterations have an impact on larynx muscles responsible for vocal fold adduction and abduction, hampering phonation stability and regularity. The main muscular articulators involved in phonation control are the cricothyroid (tensor) and thyroarytenoid (relaxer) systems, regulated by two distinct direct neuromotor pathways, activated by the precentral gyrus laryngeal control areas. These articulations control the musculus vocalis, directly responsible for regular vocal fold vibration. An indirect estimation of the muscular tension produced by inverse filtering may split into two independent channels, assumed to be the tensor and relaxer neuromotor pathways such as the differential neuromotor activity (DNMA). The amplitude distributions of both DNMA channels allow comparing phonations from PD-affected persons (PDPs) and age-matched healthy control participants (HCPs) with respect to a set of reference mid-age normative participants (RSPs). The comparisons are carried out by Jensen-Shannon distributions of PDP and HCP phonations with respect to those of RSPs. A dataset of 96 phonation samples from participants balanced by gender is used to train a set of decision tree classifiers (DTCs) to distinguish PDP from HCP phonation. The best results from 10-fold cross-validation offered accumulated mismatches of 0.09 and 0.1292 for male and female subsets. The sensitivity, specificity, and accuracy of the classification results when separating PDP from HCP phonatios were 93.33%, 88.23%, and 90.63% (male PDP versus HCP) and 92.86%, 83.33%, and 87.50% (female PDP versus HCP), providing a stratification of PDPs and HCPs by objective disease grading from explainable AI (XAI) methods.
- MeSH
- Adult MeSH
- Phonation * physiology MeSH
- Laryngeal Muscles * physiopathology MeSH
- Larynx * physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Parkinson Disease * physiopathology complications MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Exposure to benzophenone-1 (BP-1) and benzophenone-3 (BP-3), widely used as UV filters in personal care products, has been associated with adverse health effects. However, epidemiological evidence is limited and inconclusive, particularly in vulnerable populations such as teenagers. OBJECTIVE: To examine the relation between BP-1 and BP-3 concentrations and obesity, cardiometabolic biomarkers, and asthma/allergy outcomes in European teenagers, including possible sex-specific associations. METHODS: A multi-country cross-sectional study was conducted using pooled data from six aligned studies from the Human Biomonitoring for Europe Initiative (HBM4EU). Sociodemographic data, cardiometabolic biomarkers, and asthma/allergy outcomes were collected through questionnaires. Anthropometric data and BMI z-scores were calculated (n = 1339). Plasma/serum cardiometabolic biomarkers and asthma/allergy outcomes were available for a subsample (n = 173-594). Urinary BP-1 and BP-3 concentrations were adjusted for creatinine dilution using the traditional standardization (trad.) and the covariate-adjusted creatinine standardization (CAS) method. Generalized additive models, linear, logistic, and multinomial mixed models were applied, and sex-interaction terms were tested. RESULTS: Each natural log-unit increase in urinary BP-3 (CAS) concentrations was associated with higher odds of obesity in the whole population (OR: 1.20; 95%CI: 1.04-1.38). Sex-specific associations were also found with BP-1 (CAS) and BP-3 (CAS) concentrations, which were associated with higher odds of obesity in male teenagers (OR: 1.25; 95% CI: 1.01-1.55; OR: 1.34; 95%CI: 1.09-1.65, respectively). Linear mixed models showed consistent findings toward higher BMI z-scores. A negative association was found between BP-1 (CAS) concentration and serum adiponectin levels in females (% change per loge-unit increase: -3.73, 95%CI: -7.32, -0.10). BP-3 (CAS) concentrations were also associated with higher odds of non-food allergies in males (OR: 1.27; 95%CI: 1.00-1.63). Traditional creatinine adjustment showed similar or slightly attenuated estimates compared to the CAS method. CONCLUSIONS: BP-1 and BP-3 exposure was cross-sectionally associated with higher odds of obesity in European male teenagers, highlighting the need to update regulations and keep exposure levels as low as practically achievable. Longitudinal studies are needed to confirm these findings.
- MeSH
- Hypersensitivity * epidemiology MeSH
- Benzophenones * toxicity urine adverse effects MeSH
- Biomarkers blood MeSH
- Biological Monitoring MeSH
- Asthma * epidemiology chemically induced MeSH
- Humans MeSH
- Adolescent MeSH
- Obesity * epidemiology chemically induced MeSH
- Sunscreening Agents * adverse effects MeSH
- Cross-Sectional Studies MeSH
- Environmental Exposure * MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
PURPOSE: This study investigates genes contributing to late-adult corneal dystrophies (LACDs) in aged mice, with potential implications for late-onset corneal dystrophies (CDs) in humans. METHODS: The International Mouse Phenotyping Consortium (IMPC) database, containing data from 8901 knockout mouse lines, was filtered to include late-adult mice (49+ weeks) with significant (P < 0.0001) CD phenotypes. Candidate genes were mapped to human orthologs using the Mouse Genome Informatics group, with expression analyzed via PLAE and a literature review for prior CD associations. Comparative analyses of LACD genes from IMPC and established human CD genes from IC3D included protein interactions (STRING), biological processes (PANTHER), and molecular pathways (KEGG). RESULTS: Analysis identified 14 genes linked to late-adult abnormal corneal phenotypes. Of these, 2 genes were previously associated with CDs in humans, while 12 were novel. Seven of the 14 genes (50%) were expressed in the human cornea based on single-cell transcriptomics. Protein-protein interactions via STRING showed several significant interactions with known human CD genes. PANTHER analysis identified six biological processes shared with established human CD genes. Two genes (Rgs2 and Galnt9) were involved in pathways related to human corneal diseases, including cGMP-PKG signaling, mucin-type O-glycan biosynthesis, and oxytocin signaling. Other candidates were implicated in pathways such as pluripotency of stem cells, MAPK signaling, WNT signaling, actin cytoskeleton regulation, and cellular senescence. CONCLUSIONS: This study identified 14 genes linked to LACD in knockout mice, 12 of which are novel in corneal biology. These genes may serve as potential therapeutic targets for treating corneal diseases in aging human populations.
OBJECTIVES: Treponema pallidum subsp. pallidum (T. pallidum) is the etiological agent of syphilis, a sexually transmitted disease of global public health importance. The objective of this study was to introduce a novel in vitro protocol for isolation of T. pallidum directly from patients' clinical samples, eliminating the need for rabbit propagation. METHODS: Four oral and five genital swabs were collected from nine epidemiologically unrelated patients at two hospitals in Brno, Czech Republic. Swabs were submerged in TpCM-2 medium for transport. Samples were then placed on a 0.4 μm filters and incubated for 2.5 hours. During this period, spiral T. pallidum cells passed through the filter pores to the well containing TpCM-2 medium and rabbit feeder cells (Sf1Ep). Stable T. pallidum cultures (containing >1 × 107 treponemes) were achieved by subculturing every 7 days into fresh well. RESULTS: A successful protocol for in vitro isolation of T. pallidum was established. From the nine clinical specimens processed, six T. pallidum cultures (MU1-MU6) were derived after 14 to 112 days of cultivation. Five of these strains (MU1-MU5) belonged to SS14-like cluster and shared the same allelic profile 1.3.1. The remaining strain (MU6) was identified as a Nichols-like strain with an allelic profile 9.16.3. DISCUSSION: The introduced in vitro protocol enables isolation of T. pallidum from clinical material, including frozen samples, without the need for experimental rabbits. This method facilitates the isolation of contemporary, clinically relevant treponemal strains.
- MeSH
- Bacteriological Techniques * methods MeSH
- Rabbits MeSH
- Humans MeSH
- Genitalia microbiology MeSH
- Syphilis * microbiology diagnosis MeSH
- Treponema pallidum * isolation & purification genetics classification MeSH
- Mouth microbiology MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic 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
- Olfactory Bulb * metabolism MeSH
- Behavior, Animal MeSH
- Smell * physiology MeSH
- Disease Models, Animal MeSH
- Mice, Knockout * MeSH
- Mice MeSH
- Odorants * MeSH
- Fragile X Mental Retardation Protein * genetics metabolism MeSH
- Fragile X Syndrome * physiopathology genetics MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
