Early-Onset Colorectal Cancer Patients Do Not Require Shorter Intervals for Post-Surgical Surveillance Colonoscopy.

BACKGROUND: Early-onset colorectal cancer (EO-CRC), diagnosed before age 50, is rising in incidence worldwide. Although post-surgical colonoscopy surveillance strategies exist, appropriate intervals in EO-CRC remain elusive, as long-term surveillance outcomes remain scant. We sought to compare findings of surveillance colonoscopies of EO-CRC to average onset colorectal cancer (AO-CRC) patients to help define surveillance outcomes in these groups. METHODS: Single institution retrospective chart review identified EO-CRC and AO-CRC patients with colonoscopy and no evidence of disease. Surveillance intervals and time to development of advanced neoplasia (CRC and advanced polyps (adenoma/sessile serrated)) were examined. For each group, three serial surveillance colonoscopies were evaluated. Statistical analyses were performed utilizing log-ranked Kaplan-Meier method and Cox proportional hazards. RESULTS: A total of 1259 CRC patients were identified, with 612 and 647 patients in the EO-CRC and AO-CRC groups, respectively. Compared to AO-CRC patients, EO-CRC patients had a 29% decreased risk of developing advanced neoplasia from time of initial surgery to first surveillance colonoscopy (HR=0.71, 95% CI 0.52 - 1.0). Average follow-up time from surgical resection to first surveillance colonoscopy was 12.6 months for both cohorts. Overall surveillance findings differed between cohorts (p=0.003), and EO-CRC were found to have less advanced neoplasia compared to AO-CRC counterparts (12.4% vs 16.0%, respectively). Subsequent colonoscopies found that while EO-CRC patients returned for follow-up surveillance colonoscopy earlier than AO-CRC patients, the EO-CRC cohort did not have more advanced neoplasia nor non-advanced adenomas. CONCLUSIONS: EO-CRC patients do not have an increased risk of advanced neoplasia compared to AO-CRC patients and therefore do not require more frequent colonoscopy surveillance than current guidelines recommend.

Flicker and reading speed: Effects on individuals with visual sensitivity.

Flicker and patterns of stripes in the modern environment can evoke visual illusions, discomfort migraine, and seizures. We measured reading speed while striped and less striped texts were illuminated with LED lights. In Experiment 1, the lights flickered at 60 Hz and 120 Hz compared to 60 kHz (perceived as steady light). In Experiment 2, the lights flickered at 60 Hz or 600 Hz (at which frequency the phantom array is most visible), and were compared to continuous light. Two types of text were used: one containing words with high horizontal autocorrelation (striped) and another containing words with low autocorrelation (less striped). We measured the number of illusions participants saw in the Pattern Glare (PG) Test. Overall, reading speed was slowest during the 60 Hz and 600 Hz flicker and was slower when reading the high autocorrelation text. Interestingly, the low PG group showed greater effects of flicker on reading speed than the high PG group, which tended to be slower overall. In addition, reading speed in the high PG group was reduced when the autocorrelation of the text was high. These findings suggest that uncomfortable visual environments reduce reading efficiency, the more so in individuals who are visually sensitive.

Distinct genomic and immunologic tumor evolution in germline TP53-driven breast cancers.

Pathogenic germline TP53 alterations cause Li-Fraumeni Syndrome (LFS), and breast cancer is the most common cancer in LFS females. We performed first of its kind multimodal analysis of LFS breast cancer (LFS-BC) compared to sporadic premenopausal BC. Nearly all LFS-BC underwent biallelic loss of TP53 with no recurrent oncogenic variants except ERBB2 (HER2) amplification. Compared to sporadic BC, in situ and invasive LFS-BC exhibited a high burden of short amplified aneuploid segments (SAAS). Pro-apoptotic p53 target genes BAX and TP53I3 failed to be up-regulated in LFS-BC as was seen in sporadic BC compared to normal breast tissue. LFS-BC had lower CD8+ T-cell infiltration compared to sporadic BC yet higher levels of proliferating cytotoxic T-cells. Within LFS-BC, progression from in situ to invasive BC was marked by an increase in chromosomal instability with a decrease in proliferating cytotoxic T-cells. Our study uncovers critical events in mutant p53-driven tumorigenesis in breast tissue.

No trauma-related diagnosis in emergency trauma room whole-body computer tomography of patients with inconspicuous primary survey.

PURPOSE: Whole-body computer tomographic examinations (WBCT) are essential in diagnosing the severely injured. The structured clinical evaluation in the emergency trauma room, according to ATLS® and guidelines, helps to indicate the correct radiological imaging to avoid overtriage and undertriage. This retrospective, single-center study aimed to evaluate the value of WBCT in patients with an inconspicuous primary survey and whether there is any evidence for this investigation in this group of patients. METHODS: This retrospective, single-center study was conducted with patients admitted to a maximum-care hospital and supraregional trauma center in Germany and part of the TraumaNetwork DGU® in southwest Germany between January 2012 and November 2017. Hospital files were used for evaluation, and WBCT was carried out using a 32-row MSCT device from Siemens Healthineers, Volume Zoom, Erlangen, Germany. For evaluation, non-parametric procedures such as the chi-square test, U test, Fisher test, and Wilcoxon rank sum test were used to test for significance (p < 0.05). RESULTS: From 3976 patients treated with WBCT, 120 patients (3.02%) showed an inconspicuous primary survey. This examination did not reveal any trauma sequelae in any of this group. Additionally, 198 patients (4.98%) showed minor clinical symptoms in the primary survey, but no morphological trauma sequence could be diagnosed in WBCT diagnostics. Three hundred forty-two patients were not admitted as inpatients after WBCT and discharged to further outpatient treatment because there were no objectifiable reasons for inpatient treatment. Four hundred fifteen patients did not receive WBCT for, e.g., isolated extremity trauma, child, pregnancy, or death. CONCLUSION: Not one of the clinically asymptomatic patients had an imageable injury after WBCT diagnostics in this study. WBCT should only be performed in severely injured patients after clinical assessment regardless of "trauma mechanism." According to guidelines and ATLS®, the clinical examination seems to be a safe and reliable method for reasonable and responsible decision-making regarding the realization of WBCT with all well-known risk factors.

Maltose accumulation-induced cell death in Saccharomyces cerevisiae.

Pretreatment of lignocellulose yields a complex sugar mixture that potentially can be converted into bioethanol and other chemicals by engineered yeast. One approach to overcome competition between sugars for uptake and metabolism is the use of a consortium of specialist strains capable of efficient conversion of single sugars. Here, we show that maltose inhibits cell growth of a xylose-fermenting specialist strain IMX730.1 that is unable to utilize glucose because of the deletion of all hexokinase genes. The growth inhibition cannot be attributed to a competition between maltose and xylose for uptake. The inhibition is enhanced in a strain lacking maltase enzymes (dMalX2) and completely eliminated when all maltose transporters are deleted. High-level accumulation of maltose in the dMalX2 strain is accompanied by a hypotonic-like transcriptional response, while cells are rescued from maltose-induced cell death by the inclusion of an extracellular osmolyte such as sorbitol. These data suggest that maltose-induced cell death is due to high levels of maltose uptake causing hypotonic-like stress conditions and can be prevented through engineering of the maltose transporters. Transporter engineering should be included in the development of stable microbial consortia for the efficient conversion of lignocellulosic feedstocks.

Ictal-Interictal Continuum in the Pediatric Intensive Care Unit.

BACKGROUND: The ictal-interictal continuum (IIC) consists of several electroencephalogram (EEG) patterns that are common in critically ill adults. Studies focused on the IIC are limited in critically ill children and have focused primarily on associations with electrographic seizures (ESs). We report the incidence of the IIC in the pediatric intensive care unit (PICU). We then compare IIC patterns to rhythmic and periodic patterns (RPP) not meeting IIC criteria looking for associations with acute cerebral abnormalities, ES, and in-hospital mortality. METHODS: This was a retrospective review of prospectively collected data for patients admitted to the PICU at Children's National Hospital from July 2021 to January 2023 with continuous EEG. We excluded patients with known epilepsy and cerebral injury prior to presentation. All patients were screened for RPP. The American Clinical Neurophysiology Society standardized Critical Care EEG terminology for the IIC was applied to each RPP. Associations between IIC and RPP not meeting IIC criteria, with clinical and EEG variables, were calculated using odds ratios (ORs). RESULTS: Of 201 patients, 21% (42/201) had RPP and 12% (24/201) met IIC criteria. Among patients with an IIC pattern, the median age was 3.4 years (interquartile range (IQR) 0.6-12 years). Sixty-seven percent (16/24) of patients met a single IIC criterion, whereas the remainder met two criteria. ESs were identified in 83% (20/24) of patients and cerebral injury was identified in 96% (23/24) of patients with IIC patterns. When comparing patients with IIC patterns with those with RPP not qualifying as an IIC pattern, both patterns were associated with acute cerebral abnormalities (IIC OR 26 [95% confidence interval {CI} 3.4-197], p = 0.0016 vs. RPP OR 3.5 [95% CI 1.1-11], p = 0.03), however, only the IIC was associated with ES (OR 121 [95% CI 33-451], p < 0.0001) versus RPP (OR 1.3 [0.4-5], p = 0.7). CONCLUSIONS: Rhythmic and periodic patterns and subsequently the IIC are commonly seen in the PICU and carry a high association with cerebral injury. Additionally, the IIC, seen in more than 10% of critically ill children, is associated with ES. The independent impact of RPP and IIC patterns on secondary brain injury and need for treatment of these patterns independent of ES requires further study.

Synthetic Vesicles for Sustainable Energy Recycling and Delivery of Building Blocks for Lipid Biosynthesis†.

ATP is a universal energy currency that is essential for life. l-Arginine degradation via deamination is an elegant way to generate ATP in synthetic cells, which is currently limited by a slow l-arginine/l-ornithine exchange. We are now implementing a new antiporter with better kinetics to obtain faster ATP recycling. We use l-arginine-dependent ATP formation for the continuous synthesis and export of glycerol 3-phosphate by including glycerol kinase and the glycerol 3-phosphate/Pi antiporter. Exported glycerol 3-phosphate serves as a precursor for the biosynthesis of phospholipids in a second set of vesicles, which forms the basis for the expansion of the cell membrane. We have therefore developed an out-of-equilibrium metabolic network for ATP recycling, which has been coupled to lipid synthesis. This feeder-utilizer system serves as a proof-of-principle for the systematic buildup of synthetic cells, but the vesicles can also be used to study the individual reaction networks in confinement.

Comparison between Ultrasound-Guided and Palpatory Localization of the Dorsal Joint Space of the Shoulder Joint.

AIM OF THE STUDY: Arthroscopy ranks among the frequently performed interventions in orthopedics. The aim of this study was to compare the palpation technique with the ultrasound technique for locating the dorsal glenohumeral joint space (JS) in shoulder joint punctures. MATERIAL AND METHODS: Participants inexperienced in ultrasound examinations were included. Palpatory and ultrasound finding of the joint space by the participants was performed according to current recommendations and was initially demonstrated by an instructional video. The ideal point (IP) was marked under ultrasound visualization by an experienced ultrasound examinator and shoulder-elbow surgeon. Furthermore, a corridor for a safe puncture was defined. The palpatorily determined point (pdP) was marked by the participants and evaluated by means of a coordinate system. The evaluation of the sonographically determined point (sdP) was performed similarly to that of the palpatory procedure. RESULTS: Fifty-four participants were included in the study, and the mean length of work experience was 6.3 years. On average, participants had performed 16.5 punctures of the shoulder joint and 6.8 arthroscopies of the shoulder joint. The mean experience in performing sonographic examinations of the shoulder was 27.6 examinations. A total of 100 shoulder joints were examined (54 left, 46 right shoulders). The mean deviation from the ideal point (IP) for the palpatory approach was 17.1 mm with a maximum deviation of 59.5 mm; for the sonographic technique, the mean deviation was 10.3 mm (max. 30.2 mm). Overall, 22% of pdPs were within the defined corridor, while 42% of sdPs were within the target corridor. The average difference between palpatory and sonographic approaches was 9.0 mm in favor of the sonographic technique (max. 46.5 mm). A significantly greater deviation (p < 0.001) from the IP was observed with the palpatory approach than with the sonographic approach. CONCLUSION: Based on the results, the authors recommend ultrasound imaging of the shoulder joint as well as ultrasound-assisted punctures, especially for inexperienced users. Furthermore, training in ultrasound-assisted interventions should be implemented in future training curricula.

Association of epicardial adipose tissue with early structural and functional cardiac changes in Type 2 diabetes.

BACKGROUND: Dysregulated epicardial adipose tissue (EAT) may contribute to the development of heart failure in Type 2 diabetes (T2D). This study aimed to evaluate the associations between EAT volume and composition with imaging markers of subclinical cardiac dysfunction in people with T2D and no prevalent cardiovascular disease. METHODS: Prospective case-control study enrolling participants with and without T2D and no known cardiovascular disease. Two hundred and fifteen people with T2D (median age 63 years, 60 % male) and thirty-nine non-diabetics (median age 59 years, 62 % male) were included. Using computed tomography (CT), total EAT volume and mean CT attenuation, as well as, low attenuation (Hounsfield unit range -190 to -90) EAT volume were quantified by a deep learning method and volumes indexed to body surface area. Associations with cardiac magnetic resonance-derived left ventricular (LV) volumes and strain indices were assessed using linear regression. RESULTS: T2D participants had higher LV mass/volume ratio (median 0.89 g/mL [0.82-0.99] vs 0.79 g/mL [0.75-0.89]) and lower global longitudinal strain (GLS; 16.1 ± 2.3 % vs 17.2 ± 2.2 %). Total indexed EAT volume correlated inversely with mean CT attenuation. Low attenuation indexed EAT volume was 2-fold higher (18.8 cm3/m2 vs. 9.4 cm3/m2, p < 0.001) in T2D and independently associated with LV mass/volume ratio (ß = 0.002, p = 0.01) and GLS (ß = -0.03, p = 0.03). CONCLUSIONS: Higher EAT volumes seen in T2D are associated with a lower mean CT attenuation. Low attenuation indexed EAT volume is independently, but only weakly, associated with markers of subclinical cardiac dysfunction in T2D.

Method to develop a regional guide for the allergenic potential of tree pollen.

Allergic rhinitis, caused by airborne pollen, is a common disease with a great impact on the quality of life for patients and high costs for society. Prevention of high pollen concentrations in the air is relevant for creating a safe environment for allergic patients. Due to climate change, the heat in cities during the summer is a recurring problem. The local climate can be improved by using the cooling properties of trees, providing shade and cooling by evapotranspiration. When deciding which tree species will be planted, it is important to take into account the allergenicity of the pollen that the tree produces. Available guides, used all over the world, on the allergenicity of pollen are very divers in content and interpretation and not applicable for the Netherlands. In this study a method is described to develop a guide for the allergenic potential of tree pollen in a region, in this case the Netherlands. For the most common tree species in the Netherlands the scientific knowledge on the allergenicity of the pollen was collected, followed by an inventory on regional pollen abundance. Subsequently, the sensitization pattern in a patient group with possible inhalation allergy was analyzed. Based on these data allergenicity of the tree pollen was classified into five classes. Eight tree species/genera of the 61 most planted tree species in the Netherlands are considered to have a very strong to moderate allergenic potential. We propose to use this methodology to develop regional-specific guides classifying the allergenic potential of tree pollen.

The Modified Ultrasound-Assisted Method: A Study of the Correlation between Magnetic Resonance Imaging and the Ultrasound-Assisted Evaluation of the Critical Shoulder Angle.

BACKGROUND: An increased or decreased critical shoulder angle (CSA) is a known risk factor for osteoarthritis, lesions, and re-ruptures in the rotator cuff. A CSA greater than 35° correlates with degenerative rotator cuff tears, while a CSA of less than 30° correlates with osteoarthritis in the glenohumeral joint. The diagnostic gold standard for its determination is X-ray or MRI. OBJECTIVES: The primary objective of this research was to assess the viability of utilizing sonography imaging as a diagnostic tool to determine the modified critical shoulder angle (mCSA). This study aimed to investigate the feasibility and effectiveness of sonographic techniques in accurately diagnosing CSA compared to MRI. STUDY DESIGN AND METHODS: A cohort study was carried out (level of evidence 3). The CSA (MRI) and the mCSA (ultrasound) were assessed retrospectively by two independent board-certified investigators in 109 patients with shoulder pain by MRI and musculoskeletal sonography. The CSA in the MRI dataset was determined using routine protocols and then compared to the values assessed using the modified sonography-assisted method (mCSA). Both results were analyzed with linear regression to determine a possible correlation. All investigations were performed by a DEGUM (German Society for Medical Ultrasound)-certified specialist in musculoskeletal sonography. RESULTS: A total of 112 patients were included in this study, namely 40 female patients and 72 male patients with a mean age of 54.7 years at the time of the investigation. The mean CSA in MRI was 31.5° ± 3.899, and the mCSA in sonography was 30.1° ± 4.753. The inter- and intraobserver reliability for the CSA was factual with values of 0.993 and 0.967. The inter- and intraobserver reliability for mCSA was factual as well, with values of 0.989 and 0.948. The ANOVA analysis did not reveal a significant difference between the CSA and the mCSA values, and linear regression determined the R2 value to be 0.358 with p < 0.05. CONCLUSIONS: Diagnosing the mCSA using sonography is a safe and valid method. No statistically significant differences between the results in MRI and sonography could be seen. Although this is a retrospective, single-center study including only Caucasian mid-Europeans, and with the known limitations of ultrasound imaging, it nevertheless shows that sonography can be used as a simple, cheap, and fast technique to assess a modified CSA, which shows very good correlation with the standard CSA without losing the diagnostic quality.

Macromolecular Crowding, Phase Separation, and Homeostasis in the Orchestration of Bacterial Cellular Functions.

Macromolecular crowding affects the activity of proteins and functional macromolecular complexes in all cells, including bacteria. Crowding, together with physicochemical parameters such as pH, ionic strength, and the energy status, influences the structure of the cytoplasm and thereby indirectly macromolecular function. Notably, crowding also promotes the formation of biomolecular condensates by phase separation, initially identified in eukaryotic cells but more recently discovered to play key functions in bacteria. Bacterial cells require a variety of mechanisms to maintain physicochemical homeostasis, in particular in environments with fluctuating conditions, and the formation of biomolecular condensates is emerging as one such mechanism. In this work, we connect physicochemical homeostasis and macromolecular crowding with the formation and function of biomolecular condensates in the bacterial cell and compare the supramolecular structures found in bacteria with those of eukaryotic cells. We focus on the effects of crowding and phase separation on the control of bacterial chromosome replication, segregation, and cell division, and we discuss the contribution of biomolecular condensates to bacterial cell fitness and adaptation to environmental stress.

Background EEG Suppression Ratio for Early Detection of Cerebral Injury in Pediatric Cardiac Arrest.

BACKGROUND: Our objective was to assess the utility of the 1-h suppression ratio (SR) as a biomarker of cerebral injury and neurologic prognosis after cardiac arrest (CA) in the pediatric hospital setting. METHODS: Prospectively, we reviewed data from children presenting after CA and monitored by continuous electroencephalography (cEEG). Patients aged 1 month to 21 years were included. The SR, a quantitative measure of low-voltage cEEG (≤ 3 µV) content, was dichotomized as present or absent if there was > 0% suppression for one continuous hour. A multivariate logistic regression analysis was performed including age, sex, type of CA (i.e., in-hospital or out-of-hospital), and the presence of SR as a predictor of global anoxic cerebral injury as confirmed by magnetic resonance imaging (MRI). RESULTS: We included 84 patients with a median age of 4 years (interquartile range 0.9-13), 64% were male, and 49% (41/84) had in-hospital CA. Cerebral injury was seen in 50% of patients, of whom 65% had global injury. One-hour SR presence, independent of amount, predicted cerebral injury with 81% sensitivity (95% confidence interval (CI) (66-91%) and 98% specificity (95% CI 88-100%). Multivariate logistic regression analyses indicated that SR was a significant predictor of both cerebral injury (ß = 6.28, p < 0.001) and mortality (ß = 3.56, p < 0.001). CONCLUSIONS: The SR a sensitive and specific marker of anoxic brain injury and post-CA mortality in the pediatric population. Once detected in the post-CA setting, the 1-h SR may be a useful threshold finding for deployment of early neuroprotective strategies prior or for prompting diagnostic neuroimaging.

Unraveling the multiplicity of geranylgeranyl reductases in Archaea: potential roles in saturation of terpenoids.

The enzymology of the key steps in the archaeal phospholipid biosynthetic pathway has been elucidated in recent years. In contrast, the complete biosynthetic pathways for proposed membrane regulators consisting of polyterpenes, such as carotenoids, respiratory quinones, and polyprenols remain unknown. Notably, the multiplicity of geranylgeranyl reductases (GGRs) in archaeal genomes has been correlated with the saturation of polyterpenes. Although GGRs, which are responsible for saturation of the isoprene chains of phospholipids, have been identified and studied in detail, there is little information regarding the structure and function of the paralogs. Here, we discuss the diversity of archaeal membrane-associated polyterpenes which is correlated with the genomic loci, structural and sequence-based analyses of GGR paralogs.

Model-based super-resolution reconstruction for pseudo-continuous Arterial Spin Labeling.

Arterial spin labeling (ASL) is a promising, non-invasive perfusion magnetic resonance imaging technique for quantifying cerebral blood flow (CBF). Unfortunately, ASL suffers from an inherently low signal-to-noise ratio (SNR) and spatial resolution, undermining its potential. Increasing spatial resolution without significantly sacrificing SNR or scan time represents a critical challenge towards routine clinical use. In this work, we propose a model-based super-resolution reconstruction (SRR) method with joint motion estimation that breaks the traditional SNR/resolution/scan-time trade-off. From a set of differently oriented 2D multi-slice pseudo-continuous ASL images with a low through-plane resolution, 3D-isotropic, high resolution, quantitative CBF maps are estimated using a Bayesian approach. Experiments on both synthetic whole brain phantom data, and on in vivo brain data, show that the proposed SRR Bayesian estimation framework outperforms state-of-the-art ASL quantification.

Two-photon excited-state dynamics of mEGFP-linker-mScarlet-I crowding biosensor in controlled environments.

Macromolecular crowding affects many cellular processes such as diffusion, biochemical reaction kinetics, protein-protein interactions, and protein folding. Mapping the heterogeneous, dynamic crowding in living cells or tissues requires genetically encoded, site-specific, crowding sensors that are compatible with quantitative, noninvasive fluorescence micro-spectroscopy. Here, we carried out time-resolved 2P-fluorescence measurements of a new mEGFP-linker-mScarlet-I macromolecular crowding construct (GE2.3) to characterize its environmental sensitivity in biomimetic crowded solutions (Ficoll-70, 0-300 g L-1) via Förster resonance energy transfer (FRET) analysis. The 2P-fluorescence lifetime of the donor (mEGFP) was measured under magic-angle polarization, in the presence (intact) and absence (enzymatically cleaved) of the acceptor (mScarlet-I), as a function of the Ficoll-70 concentration. The FRET efficiency was used to quantify the sensitivity of GE2.3 to macromolecular crowding and to determine the environmental dependence of the mEGFP-mScarlet-I distance. We also carried out time-resolved 2P-fluorescence depolarization anisotropy to examine both macromolecular crowding and linker flexibility effects on GE2.3 rotational dynamics within the context of the Stokes-Einstein model as compared with theoretical predictions based on its molecular weight. These time-resolved 2P-fluorescence depolarization measurements and conformational population analyses of GE2.3 were also used to estimate the free energy gain upon the structural collapse in crowded environment. Our results further the development of a rational engineering design for bioenvironmental sensors without the interference of cellular autofluorescence. Additionally, these results in well-defined environments will inform our future in vivo studies of genetically encoded GE2.3 towards the mapping of the crowded intracellular environment under different physiological conditions.