Search

Background: Over half of preterm neonates with necrotizing enterocolitis (NEC) require surgery, making it essential to understand short-term postoperative outcomes and complication rates. Therefore, this study aimed to provide an overview of 30-day postoperative complications for NEC. Secondary, risk factors for minor and major short-term postoperative complications were identified. Methods: This retrospective study included all preterm infants (GA < 35w) surgically treated for NEC from 2008 to 2022. Postoperative complications were scored following the Clavien–Madadi classification. Risk factors were analyzed using multivariable logistic regression analysis. Results: In this cohort of 326 patients, 204 received a stoma, 80 had a primary anastomosis, and 32 had both. Postoperative mortality was 19.0%. In total, 186 patients experienced 238 complications (57.1%), including 118 (63.4%) major and 68 (36.6%) minor complications. Most common complications were sepsis (19.4%), stoma-related (13.3%), and wound dehiscence (11.3%). Cardiovascular support between NEC diagnosis and surgery was a significant risk factor for major complications (OR: 1.92, 95%-CI 1.19–3.08, p = 0.007) and stoma creation for minor complications (OR: 6.73, 95%-CI 2.05–22.05, p = 0.002). Conclusion: This study showed a postoperative complication rate of 57.1%. We found cardiovascular support between NEC diagnosis and surgery as risk factor for major complications and stoma creation as risk factor for minor complications. These findings provide valuable insights for improving parental counseling on NEC outcomes. Level of evidence: II [ABSTRACT FROM AUTHOR]

Objective: To evaluate the diagnostic accuracy of supplemental 3D automated breast ultrasound (ABUS) in the diagnostic work-up of BI-RADS 0 recalls. We hypothesized that 3D ABUS may reduce the benign biopsy rate. Materials and methods: In this prospective multicenter diagnostic study, screening participants recalled after a BI-RADS 0 result underwent bilateral 3D ABUS supplemental to usual care: digital breast tomosynthesis (DBT) and targeted hand-held ultrasound (HHUS). Sensitivity, specificity, positive predictive value, and negative predictive value of 3D ABUS, and DBT plus HHUS, were calculated. New 3D ABUS findings and changes of management (biopsy or additional imaging) were recorded. Results: A total of 501 women (median age 55 years, IQR [51–64]) with 525 BI-RADS 0 lesions were included between April 2018 and March 2020. Cancer was diagnosed in 45 patients. 3D ABUS sensitivity was 72.1% (95% CI [57.2–83.4%]), specificity 84.4% (95% CI [80.8–87.4%]), PPV 29.2% (95% CI [21.4–38.5%]), and NPV 97.1% 95.0–98.4%). Sensitivity of DBT plus HHUS was 100% (95% CI [90.2–100%]), specificity 71.4% (95% CI [67.2–75.2%]), PPV 23.8% (95% CI [18.1–30.5%]) and NPV 100% (95% CI [98.7–100%]). Twelve out of 43 (27.9%) malignancies in BI-RADS 0 lesions were missed on 3D ABUS, despite being detected on DBT and/or HHUS. Supplemental 3D ABUS resulted in the detection of 57 new lesions and six extra biopsy procedures, all were benign. Conclusion: 3D ABUS in the diagnostic work-up of BI-RADS 0 recalls may miss over a quarter of cancers detected with HHUS and/or DBT and should not be used to omit biopsy. Supplemental 3D ABUS increases the benign biopsy rate. Trial registration: Dutch Trial Register, available via https://www.onderzoekmetmensen.nl/en/trial/29659 Critical relevance statement: Supplemental 3D automated breast ultrasound in the work-up of BI-RADS 0 recalls may miss over a quarter of cancers detected with other methods and should not be used to omit biopsy; ABUS findings did increase benign biopsy rate. Key Points: Automated breast ultrasound (ABUS) may miss over 25% of cancers detectable by alternative methods. Don't rely solely on 3D ABUS to assess indication for biopsy. New findings with supplemental 3D ABUS increase the benign biopsy rate. [ABSTRACT FROM AUTHOR]

Gadolinium-based contrast agents (GBCA) are essential for diagnostic MRI examinations. GBCA are only used in small quantities on a per-patient basis; however, the acquisition of contrast-enhanced MRI examinations worldwide results in the use of many thousands of litres of GBCA per year. Data shows that these GBCA are present in sewage water, surface water, and drinking water in many regions of the world. Therefore, there is growing concern regarding the environmental impact of GBCA because of their ubiquitous presence in the aquatic environment. To address the problem of GBCA in the water system as a whole, collaboration is necessary between all stakeholders, including the producers of GBCA, medical professionals and importantly, the consumers of drinking water, i.e. the patients. This paper aims to make healthcare professionals aware of the opportunity to take the lead in making informed decisions about the use of GBCA and provides an overview of the different options for action. In this paper, we first provide a summary on the metabolism and clinical use of GBCA, then the environmental fate and observations of GBCA, followed by measures to reduce the use of GBCA. The environmental impact of GBCA can be reduced by (1) measures focusing on the application of GBCA by means of weight-based contrast volume reduction, GBCA with higher relaxivity per mmol of Gd, contrast-enhancing sequences, and post-processing; and (2) measures that reduce the waste of GBCA, including the use of bulk packaging and collecting residues of GBCA at the point of application. Critical relevance statement This review aims to make healthcare professionals aware of the environmental impact of GBCA and the opportunity for them to take the lead in making informed decisions about GBCA use and the different options to reduce its environmental burden. Key points • Gadolinium-based contrast agents are found in sources of drinking water and constitute an environmental risk. • Radiologists have a wide spectrum of options to reduce GBCA use without compromising diagnostic quality. • Radiology can become more sustainable by adopting such measures in clinical practice. [ABSTRACT FROM AUTHOR]

Analysis of climate policy scenarios has become an important tool for identifying mitigation strategies, as shown in the latest Intergovernmental Panel on Climate Change Working Group III report1. The key outcomes of these scenarios differ substantially not only because of model and climate target differences but also because of different assumptions on behavioural, technological and socio-economic developments2–4. A comprehensive attribution of the spread in climate policy scenarios helps policymakers, stakeholders and scientists to cope with large uncertainties in this field. Here we attribute this spread to the underlying drivers using Sobol decomposition5, yielding the importance of each driver for scenario outcomes. As expected, the climate target explains most of the spread in greenhouse gas emissions, total and sectoral fossil fuel use, total renewable energy and total carbon capture and storage in electricity generation. Unexpectedly, model differences drive variation of most other scenario outcomes, for example, in individual renewable and carbon capture and storage technologies, and energy in demand sectors, reflecting intrinsic uncertainties about long-term developments and the range of possible mitigation strategies. Only a few scenario outcomes, such as hydrogen use, are driven by other scenario assumptions, reflecting the need for more scenario differentiation. This attribution analysis distinguishes areas of consensus as well as strong model dependency, providing a crucial step in correctly interpreting scenario results for robust decision-making.A Sobol attribution analysis unveils the roles of mitigation targets, model differences and scenario assumptions in shaping climate policy scenario outcomes. [ABSTRACT FROM AUTHOR]

Purpose: In breast conserving surgery, accurate lesion localization is essential for obtaining adequate surgical margins. Preoperative wire localization (WL) and radioactive seed localization (RSL) are widely accepted methods to guide surgical excision of nonpalpable breast lesions but are limited by logistical challenges, migration issues, and legislative complexities. Radiofrequency identification (RFID) technology may offer a viable alternative. The purpose of this study was to evaluate the feasibility, clinical acceptability, and safety of RFID surgical guidance for localization of nonpalpable breast cancer. Methods: In a prospective multicentre cohort study, the first 100 RFID localization procedures were included. The primary outcome was the percentage of clear resection margins and re-excision rate. Secondary outcomes included procedure details, user experience, learningcurve, and adverse events. Results: Between April 2019 and May 2021, 100 women underwent RFID guided breast conserving surgery. Clear resection margins were obtained in 89 out of 96 included patients (92.7%), re-excision was indicated in three patients (3.1%). Radiologists reported difficulties with the placement of the RFID tag, partially related to the relatively large needle-applicator (12-gauge). This led to the premature termination of the study in the hospital using RSL as regular care. The radiologist experience was improved after a manufacturer modification of the needle-applicator. Surgical localization involved a low learning curve. Adverse events (n = 33) included dislocation of the marker during insertion (8%) and hematomas (9%). The majority of adverse events (85%) occurred using the first-generation needle-applicator. Conclusion: RFID technology is a potential alternative for non-radioactive and non-wire localization of nonpalpable breast lesions. [ABSTRACT FROM AUTHOR]

White-rot fungi are efficient degraders of the lignin moiety due to the production of extracellular enzymes. Among these are laccases, which are capable of depolymerizing lignin by oxidative processes producing low-molecular weight phenolic and aromatic compounds. Among these, vanillic, protocatechuic, benzoic, ferulic and syringic acids, -hydroxylated phenol, guaiacol and vanillin have important industrial applications, as building blocks for chemical syntheses of high-valued compounds. Kraft lignin is an industrial lignin obtained from Kraft pulping of wood. Thus, the objective of this work was to optimize the culture conditions for laccase production by Pleurotus ostreatus Florida grown on Kraft lignin, and to evaluate lignin biodegradation products. Initially, the production of laccase by this fungal strain was evaluated in a Box-Behnken design with the independent variables: lignin concentration, yeast extract and time of cultivation. A second experimental design, using two variables at three levels, was performed for assaying laccase's production exclusively using the substrate 2,6-dimethoxyphenol (2,6-DMP), and the degradation products were analyzed by LC–MS/MS. Concentration of lignin was the main variable that increased laccase production assayed against 2,6-DMP substrate. The optimal conditions for laccase production were variation of lignin and yeast extract concentrations and cultivation times: 0.87% (w/v) lignin, 4.5% (w/v) yeast extract and 10 days cultivation, respectively, resulting in a laccase titer of 5.68 U/mL, which corresponded to the value predicted by the experimental design. The lignin metabolites identified were 4-methoxycinnamaldehyde and cuminaldehyde. In addition, abscisic acid was produced; considered a stress-related hormone product of the fungus. These findings demonstrated a suitable source of fungal laccase for obtaining new metabolites 4-methoxycinnamaldehyde and cuminaldehyde from the biodegradation of Kraft lignin through fermentation. [ABSTRACT FROM AUTHOR]

Available treatments for leishmaniasis have been widely used since the 1940s but come at a high cost, variable efficacy, high toxicity, and adverse side-effects. 3,3′,5,5′-Tetramethoxy-biphenyl-4,4′-diol (TMBP) was synthesized through laccase-catalysis of 2,6-dimethoxyphenol and displayed antioxidant and anticancer activity, and is considered a potential drug candidate. Thus, this study aimed to evaluate the anti-leishmanial effect of TMBP against promastigote and amastigote forms of Leishmania (L.) amazonensis and investigated the mechanisms involved in parasite death. TMBP treatment inhibited the proliferation (IC50 0.62–0.86 µM) and induced the death of promastigote forms by generating reactive oxygen species and mitochondrial dysfunction. In intracellular amastigotes, TMBP reduced the percentage of infected macrophages, being 62.7 times more selective to the parasite (CC50 53.93 µM). TMBP did not hemolyze sheep erythrocytes; indicative of low cytotoxicity. Additionally, molecular docking analysis on two enzyme targets of L. amazonensis: trypanothione reductase (TR) and leishmanolysin (Gp63), suggested that the hydroxyl group could be a pharmacophoric group due to its binding affinity by hydrogen bonds with residues at the active site of both enzymes. TMBP was more selective to the Gp63 target than TR. This is the first report that TMBP is a promising compound to act as an anti-leishmanial agent. [ABSTRACT FROM AUTHOR]

Background: The prevalence of inflicted femur fractures in young children varies (1.5-35.2%), but these data are based on small retrospective studies with high heterogeneity. Age and mobility of the child seem to be indicators of inflicted trauma.Objective: This study describes other factors associated with inflicted and neglectful trauma that can be used to distinguish inflicted and neglectful from accidental femur fractures.Materials and Methods: This retrospective study included children (0-6 years) who presented with an isolated femur fracture at 1 of the 11 level I trauma centers in the Netherlands between January 2010 and January 2016. Outcomes were classified based on the conclusions of the Child Abuse and Neglect teams or the court. Cases in which conclusions were unavailable and there was no clear accidental cause were reviewed by an expert panel.Results: The study included 328 children; 295 (89.9%) cases were classified as accidental trauma. Inflicted trauma was found in 14 (4.3%), while 19 (5.8%) were cases of neglect. Indicators of inflicted trauma were age 0-5 months (29%, positive likelihood ratio [LR +] 8.35), 6-12 months (18%, LR + 5.98) and 18-23 months (14%, LR + 3.74). Indicators of neglect were age 6-11 months (18%, LR + 4.41) and age 18-23 months (8%, LR + 1.65). There was no difference in fracture morphology among groups.Conclusion: It is unlikely that an isolated femur fracture in ambulatory children age > 24 months is caused by inflicted trauma/neglect. Caution is advised in children younger than 24 months because that age is the main factor associated with inflicted trauma/neglect and inflicted femur fractures. [ABSTRACT FROM AUTHOR]

The oxidation process of 2,6-dimethoxyphenol (2,6-DMP) by laccase from Botryosphaeria rhodina MAMB-05 and the corresponding enzyme-mediator systems was studied using cyclic voltammetry (CV). The enzyme was classified as a high oxidation potential laccase (> 0.70) V vs. NHE) based on its Redox potential at different pHs. The cyclic voltammograms for 2,6-DMP (− 58.7 mV pH−1) showed that its oxidation potential decreased more significantly compared to the enzyme (− 50.2 mV pH−1) by varying the pH. The 2,2′-azino-bis[3-ethyl-benzothiazoline-6-sulfonic acid] diammonium salt (ABTS) and 2,2,6,6-tetramethylpiperidine 1-oxyl radical (TEMPO) mediators were effectively oxidized by laccase from B. rhodina MAMB-05. The influence of laccase on the comproportionation of ABTS and the ionic step of the oxidation of TEMPO was also studied using CV. A higher potential difference was observed between laccase and the substrate, and correlated with higher enzyme activity. For the laccase-mediator systems, there was no clear correlation of potential difference between laccase and mediators with enzyme activity towards 2,6-DMP. This observation suggests that there are other limiting parameters for enzyme activity despite Redox potential difference, especially during ionic steps of the mechanism. [ABSTRACT FROM AUTHOR]

Background: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment for patients with colorectal peritoneal metastases (CRPM). Patient selection is key to optimizing outcomes after CRS/HIPEC. The aim of this study was to determine the prognostic value of ascites diagnosed on preoperative imaging. Methods: A prospective database of patients eligible for CRS/HIPEC between 2010 and 2020 was retrospectively analyzed. The presence of ascites, postoperative complications, overall survival (OS), disease-free survival (DFS), and completeness of cytoreduction were assessed. Univariable and multivariable logistic regression was performed to identify independent predictors for outcome. Results: Of the 235 included patients, 177 (75%) underwent CRS/HIPEC while 58 (25%) were not eligible for CRS/HIPEC. In 42 of the 177 patients (24%) who underwent CRS/HIPEC, ascites was present on preoperative computed tomography (CT) imaging. Peritoneal Cancer Index (PCI) score was significantly higher in patients with preoperative ascites compared with patients without (11 [range 2–30] vs. 9 [range 0–28], respectively; p = 0.011) and complete cytoreduction was more often achieved in patients without ascites (96.3% vs. 85.7%; p = 0.007). There was no significant difference in median DFS and OS after CRS/HIPEC between patients with and without ascites {10 months (95% confidence interval [CI] 7.1–12.9) vs. 9 months (95% CI 7.2–10.8), and 25 months (95% 9.4–40.6) vs. 27 months (95% CI 22.4–31.6), respectively}. Conclusions: Ascites on preoperative imaging was not associated with worse survival in CRS/HIPEC patients with CRPM. Therefore, excluding patients from CRS/HIPEC based merely on the presence of ascites is not advisable. [ABSTRACT FROM AUTHOR]

Railway systems form an important means of transport across the world. However, congestions or disruptions may significantly decrease these systems' efficiencies, making predicting and understanding the resulting train delays a priority for railway organisations. Delays are studied in a wide variety of models, which usually simulate trains as discrete agents carrying delays. In contrast, in this paper, we define a novel model for studying delays, where they spread across the railway network via a diffusion-like process. This type of modelling has various advantages such as quick computation and ease of applying various statistical tools like spectral methods, but it also comes with limitations related to the directional and discrete nature of delays and the trains carrying them. We apply the model to the Belgian railways and study its performance in simulating the delay propagation in severely disrupted railway situations. In particular, we discuss the role of spatial aggregation by proposing to cluster the Belgian railway system into sets of stations and adapt the model accordingly. We find that such aggregation significantly increases the model's performance. For some particular situations, non-trivial optimal levels of spatial resolution are found on which the model performs best. Our results show the potential of this type of delay modelling to understand large-scale properties of railway systems. [ABSTRACT FROM AUTHOR]

Human social behavior plays a crucial role in how pathogens like SARS-CoV-2 or fake news spread in a population. Social interactions determine the contact network among individuals, while spreading, requiring individual-to-individual transmission, takes place on top of the network. Studying the topological aspects of a contact network, therefore, not only has the potential of leading to valuable insights into how the behavior of individuals impacts spreading phenomena, but it may also open up possibilities for devising effective behavioral interventions. Because of the temporal nature of interactions—since the topology of the network, containing who is in contact with whom, when, for how long, and in which precise sequence, varies (rapidly) in time—analyzing them requires developing network methods and metrics that respect temporal variability, in contrast to those developed for static (i.e., time-invariant) networks. Here, by means of event mapping, we propose a method to quantify how quickly agents mingle by transforming temporal network data of agent contacts. We define a novel measure called contact sequence centrality, which quantifies the impact of an individual on the contact sequences, reflecting the individual's behavioral potential for spreading. Comparing contact sequence centrality across agents allows for ranking the impact of agents and identifying potential 'behavioral super-spreaders'. The method is applied to social interaction data collected at an art fair in Amsterdam. We relate the measure to the existing network metrics, both temporal and static, and find that (mostly at longer time scales) traditional metrics lose their resemblance to contact sequence centrality. Our work highlights the importance of accounting for the sequential nature of contacts when analyzing social interactions. [ABSTRACT FROM AUTHOR]

Railway systems occasionally get into a state of being out-of-control, meaning that barely any train is running, even though the required resources (infrastructure, rolling stock and crew) are available. Because of the large number of affected resources and the absence of detailed, timely and accurate information, currently existing disruption management techniques cannot be applied in out-of-control situations. Most of the contemporary approaches assume that there is only one single disruption with a known duration, that all information about the resources is available, and that all stakeholders in the operations act as expected. Another limitation is the lack of knowledge about why and how disruptions accumulate and whether this process can be predicted. To tackle these problems, we develop a multidisciplinary framework combining techniques from complexity science and operations research, aiming at reducing the impact of these situations and—if possible—avoiding them. The key elements of this framework are (i) the generation of early warning signals for out-of-control situations, (ii) isolating a specific region such that delay stops propagating, and (iii) the application of decentralized decision making, more suited for information-sparse out-of-control situations. [ABSTRACT FROM AUTHOR]

Contrast media are essential for diagnostic and interventional procedures. Iodinated contrast media are the most commonly used agents, with CT requiring the largest overall quantities. Data show that these iodinated contrast media are found in sewage water, surface water and drinking water in many regions in the world. Because standard drinking water purification techniques only provide poor to moderate removal of iodinated contrast media, these substances pose a problem for drinking water preparation that has not yet been solved. There is a growing body of evidence supporting the negative environmental effects of iodinated contrast media via their breakdown products. The environmental impact of iodinated contrast media can be mitigated by measures focusing on the application of contrast media or the excretion of contrast media. Measures with respect to contrast application include reducing the utilization of contrast media, reducing the waste of contrast media and collecting residues of contrast media at the point of application. The amount of contrast media excreted into the sewage water can be decreased by introducing urine bags and/or special urine collection and waste-water processing techniques in the hospital. To tackle the problem of contrast media in the water system in its entirety, it is necessary for all parties involved to cooperate, from the producer of contrast medium to the consumer of drinking water. This paper aims to make health professionals aware of the opportunity to take the lead now in more conscious decisions regarding use of contrast media and gives an overview of the different perspectives for action. [ABSTRACT FROM AUTHOR]

Purpose: Between 0.1—3% of injured children who present at a hospital emergency department ultimately die as a result of their injuries. These events are typically reported as unnatural causes of death and may result from either accidental or non-accidental trauma (NAT). Examples of the latter include trauma that is inflicted directly or resulting from neglect. Although consultation with a forensic physician is mandatory for all deceased children, the prevalence of fatal inflicted trauma or neglect among children is currently unclear. Methods: This is a retrospective study that included children (0–18 years) who presented and died at one of the 11 Level I trauma centers in the Netherlands between January 1, 2014, and January 1, 2019. Outcomes were classified based on the conclusions of the Child Abuse and Neglect team or those of forensic pathologists and/or the court in cases referred for legally mandated autopsies. Cases in which conclusions were unavailable and there was no clear accidental cause of death were reviewed by an expert panel. Results: The study included 175 cases of childhood death. Seventeen (9.7%) of these children died due to inflicted trauma (9.7%), 18 (10.3%) due to neglect, and 140 (80%) due to accidents. Preschool children (< 5 years old) were significantly more likely to present with injuries due to inflicted trauma and neglect compared to older children (44% versus 6%, p < 0.001, odds ratio [OR] 5.80, 95% confidence interval [CI] 2.66–12.65). Drowning accounted for 14 of the 18 (78%) pediatric deaths due to neglect, representing 8% of the total cases. Postmortem radiological studies and autopsies were performed on 37 (21%) of all cases of childhood death. Conclusion: One of every five pediatric deaths in our nationwide Level I trauma center study was attributed to NAT; 44% of these deaths were the result of trauma experienced by preschool-aged children. A remarkable number of fatal drownings were due to neglect. Postmortem radiological studies and autopsies were performed in only one-fifth of all deceased children. The limited use of postmortem investigations may have resulted in missed cases of NAT, which will result in an overall underestimation of fatal NAT experienced by children. [ABSTRACT FROM AUTHOR]

Railway systems provide pivotal support to modern societies, making their efficiency and robustness important to ensure. However, these systems are susceptible to disruptions and delays, leading to accumulating economic damage. The large spatial scale of delay spreading typically make it difficult to distinguish which regions will ultimately affected from an initial disruption, creating uncertainty for risk assessment. In this paper, we identify geographical structures that reflect how delay spreads through railway networks. We do so by proposing a graph-based, hybrid schedule and empirical-based model for delay propagation and apply spectral clustering. We apply the model to four European railway systems: the Netherlands, Germany, Switzerland and Italy. We characterize these geographical delay structures in the railway systems of these countries and interpret these regions in terms of delay severity and how dynamically disconnected they are from the rest. The method also allows us to point out important differences between these countries' railway systems. For practitioners, such geographical characterization of railways provides natural boundaries for local decision-making structures and risk assessment. [ABSTRACT FROM AUTHOR]

Background/objectives: Despite considerable literature supporting the potential health benefits of reducing postprandial glucose (PPG), and insulin (PPI) exposures, the size of a clinically relevant reduction is currently unknown. We performed a systematic review and meta-analysis to quantify effects of alpha-glucosidase-inhibiting (AGI) drugs on acute PPG and PPI responses. Methods: We searched EMBASE and MEDLINE until March 13, 2018 for controlled studies using AGI drugs together with a standardized carbohydrate load or mixed meal. The mean incremental PPG and PPI levels were calculated as outcomes. Meta-analyses, stratified by diabetes state, were performed by using random effects models. Results: The 66 included publications comprised 127 drug-control comparisons for PPG, and 106 for PPI, mostly testing acarbose or miglitol. The absolute effects on PPG were larger among individuals with diabetes (−1.5 mmol/l mean PPG [95% CI −1.9, −1.1] by acarbose, and −1.6 [−1.9, −1.4] by miglitol) as compared to individuals without diabetes (−0.4 [95% CI −0.5, −0.3] by acarbose, and −0.6 [−0.8, −0.4] by miglitol). Relative reductions in PPG by both drugs were similar for diabetic and non-diabetic individuals (43−54%). Acarbose and miglitol also significantly reduced mean PPI, with absolute and relative reductions being largest among individuals without diabetes. Conclusions: The present meta-analyses provide quantitative estimates of reductions of PPG and PPI responses by AGI drugs in diabetes and non-diabetic individuals. These data can serve as benchmarks for clinically relevant reductions in PPG and PPI via drug or diet and lifestyle interventions. [ABSTRACT FROM AUTHOR]

Little information is available in the literature concerning the kinetics of the production of exopolysaccharides (EPS). The kinetics of growth, substrate consumption and lasiodiplodan (LAS) production by the filamentous fungus Lasiodiplodia theobromae MMPI were studied in a new bioreactor design (Low-Shear Aerated and Agitated Bioreactor; LSAAB) using media based on glucose and glycerol. The kinetic parameters of cultivation were compared with fermentations conducted in a stirred tank bioreactor (STR) and in shake flasks. Cultivation in LSAAB using glucose resulted in 3.17 ± 0.16 g.L−1 of LAS, a value lower than that obtained in shake-flasks (6.49 ± 0.03 g.L−1), but somewhat higher than obtained in STR (0.70 ± 0.12 g.L−1). When glycerol was used as substrate, the production of LAS was less effective than glucose. From the fungal biomass produced, as well as the related growth kinetic parameters (YX/S and QX), fungal growth was more efficient in LSAAB. Lasiodiplodan production by L. theobromae MMPI from glycerol was accelerated by an increase in broth pH during cultivation, and the behavior was opposite (decreased pH) when using glucose. LSAAB proved to be promising for the production of LAS by the fungus studied. Although glucose was shown to be the better substrate for the production of LAS, glycerol, as a fermentation substrate, has potential of a less-expensive medium for cultivating the fungus. [ABSTRACT FROM AUTHOR]

A photoelectrochemical biosensing strategy for the highly sensitive detection of the flavonoid rutin was developed by synergizing the photoelectrocatalytic properties of hematite (α-Fe2O3) decorated with palladium nanoparticles (PdNPs) and the biocatalysis towards laccase-based reactions. The integration of α-Fe2O3.PdNPs with a polyphenol oxidase as a biorecognition element yields a novel biosensing platform. Under visible light irradiation, the photoactive biocomposite can generate a stable photocurrent, which was found to be directly dependent upon the concentration of rutin. Under the optimal experimental conditions, the cathodic photocurrent, measured at 0.33 V vs. Ag/AgCl, from the square-wave voltammograms presented a linear dependence on the rutin concentration within the range of 0.008–30.0 × 10−8 mol L−1 (sensitivity: 1.7 μA·(× 10−8 M−1)·cm−2), with an experimental detection limit (S/N = 3) of 8.4 × 10−11 mol L−1. The proposed biosensor device presented good selectivity towards rutin in the presence of various organic compounds and inorganic ions, demonstrating the potential application of this biosensing platform in complex matrices. This bioanalytical device also exhibited excellent operational and analytical properties, such as intra-day (standard deviation, SD = 0.21%) and inter-day (SD = 1.30%) repeatability, and long storage stability (SD = 2.80% over 30 days). Graphical abstract [ABSTRACT FROM AUTHOR]

Injection of silicate grouting materials is widely used to create temporary horizontal layers for reducing inflow of groundwater at construction sites, in regions with shallow water tables. The erosion of a grouting layer was investigated by means of analytical solutions for groundwater flow and transport within a pit after construction finished. Erosion is assumed to occur by dissolution of the temporary injection layer and subsequent advective transport. Thereby, the hydraulic conductivity changes with time. This paper presents novel analytical solutions and approximate solutions for the major fluxes in the construction pit as a function of the domain settings, aquifer gradient and hydraulic conductivity. In addition, the mass flux and the dilution ratio of erosion-related components leaving the construction pit and entering the aquifer are quantified. Derived solutions are verified against numerical simulations. A sensitivity study shows the impact of domain settings on fluxes and dilution ratio. The results confirm that mass flux of grout components increases with ongoing erosion. Thus, its effect on groundwater quality increases with time after construction ceased. [ABSTRACT FROM AUTHOR]

Soybean molasses was studied for the first time as a raw material for the fermentative production of (1 → 6)-β-d-glucan (lasiodiplodan) by Lasiodiplodia theobromae MMPI fungus. The work included characterization of soybean molasses, assessment of cultivation medium and nutritional supplementation, saccharification, fermentation of unhydrolyzed and hydrolyzed molasses, and characterization of lasiodiplodan. Crude soybean molasses showed high concentrations of monosaccharides (glucose: 13.26 g/L, galactose: 9.53 g/L and fructose: 1.99 g/L) and oligosaccharides (sucrose: 74.51 g/L, raffinose: 96.58 g/L, and stachyose: 114.02 g/L). Clarification of molasses promoted reduction of 60% of the total phenolic contents, and showed high-nutritional quality not requiring medium supplementation for fungal growth and lasiodiplodan production. Lasiodiplodia theobromae was able to assimilate the sugars from molasses (YC: 98.25%), including the oligosaccharides, thus no need for prior acid-hydrolysis for saccharification. Maximum production (1.06 g/L), yield (0.13 g/g) and volumetric productivity of lasiodiplodan (0.01 g/L h) were verified in fermentations using unhydrolyzed molasses. Both lasiodiplodan samples demonstrated high thermal stability, and presented three stages of mass-loss; the first at 150 ºC, followed by two events between 250 and 525 °C. FT-IR spectra showed characteristic signs of lasiodiplodan including bands at 1060 and 1600 cm−1 corresponding to symmetrical stretching of C–O–C (characteristic group of sugars) and glucose ring vibration, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Little is known about the impact of 70-gene signature (70-GS) use on patients' chemotherapy decision-making. The primary aim of this study was to evaluate the impact of 70-GS use on patients' decisions to undergo chemotherapy. The perceived decision conflict during decision-making was a secondary objective of the study. Methods: Patients operated for estrogen receptor positive early breast cancer were asked to fill out a questionnaire probing their inclination to undergo chemotherapy before deployment of the 70-GS test. After disclosure of the 70-GS result patients were asked about their decision regarding chemotherapy. Patients' decisional conflict was measured using the 16-item decisional conflict scale (DCS); scores < 25 are associated with a persuaded decision while a score > 37.5 implies that one feels unsure about a choice. Results: Between January 1th 2017 and December 31th 2018, 106 patients completed both questionnaires. Before deployment of the 70-GS, 58% of patients (n = 62) formulated a clear treatment preference, of whom 21 patients (34%) changed their opinion on treatment with chemotherapy following the 70-GS. The final decision regarding chemotherapy was in line with the 70-GS result in 90% of patients. The percentage of patients who felt unsure about their preference to be treated with chemotherapy decreased from 42 to 5% after disclosure of the 70-GS. The mean total DCS significantly decreased from pre-test to post-test from 35 to 23, irrespective of the risk estimate (p < 0.001). Conclusion: Deployment of the 70-GS changed patients' inclination to undergo adjuvant chemotherapy in one third of patients and decreased patients' decisional conflict. [ABSTRACT FROM AUTHOR]

The ascomycete Neodeightonia phoenicum CMIB-151 was isolated from bracts of a palm tree (Syagrus romanzoffiana) in Brazil, and identified by molecular techniques. This is the first report of the isolation of this fungus in South America, and for the first time this fungus has been described as producing an exopolysaccharide (EPS). Different carbon (glucose, fructose, sucrose, maltose, lactose, starch) and nitrogen (yeast extract, peptone, urea, ammonium sulfate) sources were evaluated for the production of EPS. Sucrose and peptone resulted in high production and yield of EPS. High production of EPS occurred at pH 6.0 and 8.0, and acidic conditions (initial pH 5.0) promoted higher mycelial growth. The EPS produced showed a high degree of purity, emulsifying activity and a high water- and oil-holding capacity; important technological properties for industrial applications. FT-IR and 13C-NMR (CP/MAS) analyzes showed typical spectra of carbohydrates containing six-carbon sugar in its structure, and the presence of β-glycosidic configuration with 3-O-substitution. The isolated EPS exhibited remarkable thermal stability. [ABSTRACT FROM AUTHOR]

We digitally transformed and analyzed ICE Facility Significant Incident Reports from 2019 to 2022[4], produced as annual rolling retrospective reports detailing the monthly count of medical, mental health, disciplinary, and non-medical, non-mental health administrative SC placements from 128 active US immigration detention facilities. Beyond minimizing (if not eliminating) the use of SC altogether, ICE must better redirect individuals who have serious mental health conditions into intensive mental health care rather than SC. The practice of solitary confinement (SC) is so detrimental to mental health that the United Nations has determined that SC lasting greater than 15 days constitutes torture[1]. [Extracted from the article]

Background/objectives: Currently, there are no widely accepted cut-off points to categorize patients as sarcopenic (low skeletal muscle mass) or myosteatotic based on computed tomography (CT) measurements. Moreover, little is known about skeletal muscle mass in healthy subjects, particularly in a Western-European population.Subjects/methods: Skeletal muscle mass (skeletal muscle index, cm2/m2) and density (Hounsfield units, HU) at the level of the third lumbar vertebra were measured on contrast-enhanced CT images in live kidney donors with an age range of 18-86 years, who may be considered as healthy subjects, from 2010 to 2015. Differences between sex, body mass index (BMI), age groups, and American Society of Anesthesiologists (ASA) classification were assessed. Mann-Whitney U and Kruskal-Wallis tests were used to compare groups.Results: Of the 1073 included patients, 499 (46.5%) were male and the median age and BMI were 51 years and 25.4 kg/m2, respectively. Male gender, increased age, and increased BMI were significantly associated with both skeletal muscle mass and density. Nomograms including these parameters were developed to calculate the estimated skeletal muscle mass and density of a healthy subject and the lower bound of the 90% prediction interval (p5) values were provided.Conclusions: Skeletal muscle density and mass were significantly associated with sex, age, and BMI in a large cohort of healthy Western-European subjects. The newly developed nomograms may be used to calculate the estimated healthy skeletal muscle mass for individuals in patient populations. [ABSTRACT FROM AUTHOR]

The coconut kernel-associated fungus, Lasiodiplodia theobromae VBE1, was grown on coconut cake with added coconut oil as lipase inducer under solid-state fermentation conditions. The extracellular-produced lipases were purified and resulted in two enzymes: lipase A (68,000 Da)—purified 25.41-fold, recovery of 47.1%—and lipase B (32,000 Da)—purified 18.47-fold, recovery of 8.2%. Both lipases showed optimal activity at pH 8.0 and 35 °C, were activated by Ca2+, exhibited highest specificity towards coconut oil and p-nitrophenyl palmitate, and were stable in iso-octane and hexane. Ethanol supported higher lipase activity than methanol, and n-butanol inactivated both lipases. Crude lipase immobilized by entrapment within 4% (w/v) calcium alginate beads was more stable than the crude-free lipase preparation within the range pH 2.5-10.0 and 20-80 °C. The immobilized lipase preparation was used to catalyze the transesterification/methanolysis of coconut oil to biodiesel (fatty acyl methyl esters (FAMEs)) and was quantified by gas chromatography. The principal FAMEs were laurate (46.1%), myristate (22.3%), palmitate (9.9%), and oleate (7.2%), with minor amounts of caprylate, caprate, and stearate also present. The FAME profile was comparatively similar to NaOH-mediated transesterified biodiesel from coconut oil, but distinctly different to petroleum-derived diesel. This study concluded that Lasiodiplodia theobromae VBE1 lipases have potential for biodiesel production from coconut oil. [ABSTRACT FROM AUTHOR]

Background/objectives: A low bioelectrical impedance analysis (BIA)-derived phase angle (PA) predicts morbidity and mortality in different patient groups. An association between PA and long-term mortality in ICU patients has not been demonstrated before. The purpose of the present study was to determine whether PA on ICU admission independently predicts 90-day mortality.Subjects/ Methods: This prospective observational study was performed in a mixed university ICU. BIA was performed in 196 patients within 24 h of ICU admission. To test the independent association between PA and 90-day mortality, logistic regression analysis was performed using the APACHE IV predicted mortality as confounder. The optimal cutoff value of PA for mortality prediction was determined by ROC curve analysis. Using this cutoff value, patients were categorized into low or normal PA group and the association with 90-day mortality was tested again.Results: The PA of survivors was higher than of the non-survivors (5.0° ± 1.3° vs. 4.1° ± 1.2°, p < 0.001). The area under the ROC curve of PA for 90-day mortality was 0.70 (CI 0.59-0.80). PA was associated with 90-day mortality (OR = 0.56, CI: 0.38-0.77, p = 0.001) on univariate logistic regression analysis and also after adjusting for BMI, gender, age, and APACHE IV on multivariable logistic regression (OR = 0.65, CI: 0.44-0.96, p = 0.031). A PA < 4.8° was an independent predictor of 90-day mortality (adjusted OR = 3.65, CI: 1.34-9.93, p = 0.011).Conclusions: Phase angle at ICU admission is an independent predictor of 90-day mortality. This biological marker can aid in long-term mortality risk assessment of critically ill patients. [ABSTRACT FROM AUTHOR]

When assessing the perceptual abilities of children, researchers tend to use psychophysical techniques designed for use with adults. However, children’s poorer attentiveness might bias the threshold estimates obtained by these methods. Here, we obtained speed discrimination threshold estimates in 6- to 7-year-old children in UK Key Stage 1 (KS1), 7- to 9-year-old children in Key Stage 2 (KS2), and adults using three psychophysical procedures: QUEST, a 1-up 2-down Levitt staircase, and Method of Constant Stimuli (MCS). We estimated inattentiveness using responses to “easy” catch trials. As expected, children had higher threshold estimates and made more errors on catch trials than adults. Lower threshold estimates were obtained from psychometric functions fit to the data in the QUEST condition than the MCS and Levitt staircases, and the threshold estimates obtained when fitting a psychometric function to the QUEST data were also lower than when using the QUEST mode. This suggests that threshold estimates cannot be compared directly across methods. Differences between the procedures did not vary significantly with age group. Simulations indicated that inattentiveness biased threshold estimates particularly when threshold estimates were computed as the QUEST mode or the average of staircase reversals. In contrast, thresholds estimated by post-hoc psychometric function fitting were less biased by attentional lapses. Our results suggest that some psychophysical methods are more robust to attentiveness, which has important implications for assessing the perception of children and clinical groups. [ABSTRACT FROM AUTHOR]

Purpose : Endothelial dysfunction and low-grade inflammation are key phenomena in the pathobiology of cardiovascular disease (CVD). Their dietary modification might explain the observed reduction in CVD that has been associated with a healthy diet rich in fruit, vegetables and fish, low in dairy products and with moderate alcohol and red wine consumption. We investigated the associations between the above food groups and endothelial dysfunction and low-grade inflammation in a population-based cohort of Dutch elderly individuals.Methods: Diet was measured by food frequency questionnaire (n = 801; women = 399; age 68.5 ± 7.2 years). Endothelial dysfunction was determined (1) by combining von Willebrand factor, and soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1, endothelial selectin and thrombomodulin, using Z-scores, into a biomarker score and (2) by flow-mediated vasodilation (FMD), and low-grade inflammation by combining C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumour necrosis factor α and sICAM-1 into a biomarker score, with smaller FMD and higher scores representing more dysfunction and inflammation, respectively. We used linear regression analyses to adjust associations for sex, age, energy, glucose metabolism, body mass index, smoking, prior CVD, educational level, physical activity and each of the other food groups.Results: Moderate [β (95% CI) −0.13 (−0.33; 0.07)] and high [−0.22 (−0.45; −0.003)] alcohol consumption, and red wine [−0.16 (−0.30; −0.01)] consumption, but none of the other food groups, were associated with a lower endothelial dysfunction biomarker score and a greater FMD. The associations for FMD were, however, not statistically significant. Only red wine consumption was associated with a lower low-grade inflammation biomarker score [−0.18 (−0.33; −0.04)].Conclusions: Alcohol and red wine consumption may favourably influence processes involved in atherothrombosis. [ABSTRACT FROM AUTHOR]

Background: Chronic cardiometabolic diseases, including cardiovascular disease (CVD), type 2 diabetes (T2D) and chronic kidney disease (CKD), share many modifiable risk factors and can be prevented using combined prevention programs. Valid risk prediction tools are needed to accurately identify individuals at risk.Objective: We aimed to validate a previously developed non-invasive risk prediction tool for predicting the combined 7-year-risk for chronic cardiometabolic diseases.Design: The previously developed tool is stratified for sex and contains the predictors age, BMI, waist circumference, use of antihypertensives, smoking, family history of myocardial infarction/stroke, and family history of diabetes. This tool was externally validated, evaluating model performance using area under the receiver operating characteristic curve (AUC)-assessing discrimination-and Hosmer-Lemeshow goodness-of-fit (HL) statistics-assessing calibration. The intercept was recalibrated to improve calibration performance.Participants: The risk prediction tool was validated in 3544 participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab).Key Results: Discrimination was acceptable, with an AUC of 0.78 (95% CI 0.75-0.81) in men and 0.78 (95% CI 0.74-0.81) in women. Calibration was poor (HL statistic: p < 0.001), but improved considerably after intercept recalibration. Examination of individual outcomes showed that in men, AUC was highest for CKD (0.85 [95% CI 0.78-0.91]) and lowest for T2D (0.69 [95% CI 0.65-0.74]). In women, AUC was highest for CVD (0.88 [95% CI 0.83-0.94)]) and lowest for T2D (0.71 [95% CI 0.66-0.75]).Conclusions: Validation of our previously developed tool showed robust discriminative performance across populations. Model recalibration is recommended to account for different disease rates. Our risk prediction tool can be useful in large-scale prevention programs for identifying those in need of further risk profiling because of their increased risk for chronic cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Major storm systems over Europe frequently have a tropical origin. This paper analyses the characteristics and dynamics of such cyclones in the observational record, using MERRA reanalysis data for the period 1979-2013. By stratifying the cyclones along three key phases of their development (tropical phase, extratropical transition and final re-intensification), we identify four radically different life cycles: the tropical cyclone and extratropical cyclone life cycles, the classic extratropical transition and the warm seclusion life cycle. More than 50% of the storms reaching Europe from low latitudes follow the warm seclusion life cycle. It also contains the strongest cyclones. They are characterized by a warm core and a frontal T-bone structure, with a northwestward warm conveyor belt and the effects of dry intrusion. Rapid deepening occurs in the latest phase, around their arrival in Europe. Both baroclinic instability and release of latent heat contribute to the strong intensification. The pressure minimum occurs often a day after entering Europe, which enhances the potential threat of warm seclusion storms for Europe. The impact of a future warmer climate on the development of these storms is discussed. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Glycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA, fasting insulin and HOMA-IR with incident type 2 diabetes mellitus. Methods: The study population included 1349 participants aged 50-75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations. Results: After a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA, 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA with incident diabetes were non-linear, rising more steeply at higher values. Conclusions/interpretation: FPG was most strongly associated with incident diabetes, followed by 2hPG, HbA, HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers. [ABSTRACT FROM AUTHOR]

Aims/Hypothesis: The relationships between smoking and glycaemic variables have not been well explored. We compared HbA 1c, fasting plasma glucose (FPG) and 2 h plasma glucose (2H-PG) in current, ex- and never-smokers. Methods: This meta-analysis used individual data from 16,886 men and 18,539 women without known diabetes in 12 DETECT-2 consortium studies and in the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) and Telecom studies. Means of three glycaemic variables in current, ex- and never-smokers were modelled by linear regression, with study as a random factor. The I2 statistic was used to evaluate heterogeneity among studies. Results: HbA 1c was 0.10% (95% CI 0.08, 0.12) (1.1 mmol/mol [0.9, 1.3]) higher in current smokers and 0.03% (0.01, 0.05) (0.3 mmol/mol [0.1, 0.5]) higher in ex-smokers, compared with never-smokers. For FPG, there was no significant difference between current and never-smokers (−0.004 mmol/l [−0.03, 0.02]) but FPG was higher in ex-smokers (0.12 mmol/l [0.09, 0.14]). In comparison with never-smokers, 2H-PG was lower (−0.44 mmol/l [−0.52, −0.37]) in current smokers, with no difference for ex-smokers (0.02 mmol/l [−0.06, 0.09]). There was a large and unexplained heterogeneity among studies, with I2 always above 50%; I2 was little changed after stratification by sex and adjustment for age and BMI. In this study population, current smokers had a prevalence of diabetes that was 1.30% higher as screened by HbA 1c and 0.52% lower as screened by 2H-PG, in comparison with never-smokers. Conclusion/interpretation: Across this heterogeneous group of studies, current smokers had a higher HbA 1c and lower 2H-PG than never-smokers. This will affect the chances of smokers being diagnosed with diabetes. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES:Lower circulating polyunsaturated fatty acids (PUFAs) may induce loss of heart function. We investigated whether lower concentrations of n-3 and n-6 PUFAs were associated with less favourable echocardiographic measures and higher heart rate in older Caucasians, cross-sectionally and after 7 years of follow-up.SUBJECTS/METHODS:We used data from the Hoorn Study, a population-based cohort. Cross-sectional data were available for 621 participants and longitudinal data for 336 participants. Mean age was 68.6±6.8 years at baseline. We performed linear regression analyses using n-3 and n-6 PUFAs quartiles-assayed by gas liquid chromatography-with left ventricular ejection fraction (LVEF), left ventricular mass index, left atrial volume index and heart rate.RESULTS:In multivariable analyses (regression coefficient (95% confidence interval)), the lowest eicosapentaenoic acid and docosahexaenoic acid quartiles compared with the highest quartiles were cross-sectionally associated with lower LVEF. Lower eicosapentaenoic acid and docosahexaenoic acid concentrations were associated with higher heart rate: 3.7 b.p.m. (1.5, 6.0; P for trend <0.001) and 3.4 b.p.m. (1.2, 5.6; P for trend 0.001), respectively. Multivariate longitudinal analyses showed a significant trend across quartiles for alpha-linolenic acid in relation to LVEF. The lowest linoleic acid quartile was significantly associated with a decreased LVEF of −4.0% compared with the highest quartile.CONCLUSIONS:This study found no strong evidence of longitudinal associations of eicosapentaenoic acid and docosahexaenoic acid with echocardiographic measures, however, lower concentrations of alpha-linolenic acid and linoleic acid were associated with decreased LVEF. These results provide evidence for a potential protective role of alpha-linolenic acid and linoleic acid in relation to systolic function. [ABSTRACT FROM AUTHOR]

Effects of a cognitive behavioural treatment (CBT) in type 2 diabetes patients were studied in a randomised controlled trial. Patients were recruited from a diabetes care system (DCS). The intervention group (n = 76) received managed care from the DCS and CBT. The control group (n = 78) received managed care only. Effects on risk of developing coronary heart disease (CHD), clinical characteristics, lifestyle, determinants of behaviour change, quality of life, and depression were assessed after 6 and 12 months. The intervention did not result in a significant reduction of CHD risk (difference between intervention and control group was −0.32 % (95 % CI: −2.27; 1.63). The amount of heavy physical activity increased significantly in the intervention group at 6 months [intervention versus control group was 20.14 min/day (95 % CI: 4.6; 35.70)]. Quality of life and level of depression improved as well. All effects disappeared after 6 months. No effects were found on clinical characteristics. [ABSTRACT FROM AUTHOR]

Purpose: Aim was to evaluate the accuracy of computed tomography colonography (CTC) for detection of colorectal neoplasia in a Fecal Occult Blood Test (FOBT) positive screening population.Methods: In three different institutions, consecutive FOBT positives underwent CTC after laxative free iodine tagging bowel preparation followed by colonoscopy with segmental unblinding. Each CTC was read by two experienced observers. For CTC and for colonoscopy the per-polyp sensitivity and per-patient sensitivity and specificity were calculated for detection of carcinomas, advanced adenomas, and adenomas.Results: In total 22 of 302 included FOBT positive participants had a carcinoma (7%) and 137 had an adenoma or carcinoma ≥10 mm (45%). CTC sensitivity for carcinoma was 95% with one rectal carcinoma as false negative finding. CTC sensitivity for advanced adenomas was 92% (95% CI: 88-96) vs. 96% (95% CI: 93-99) for colonoscopy (P = 0.26). For adenomas and carcinomas ≥10 mm the CTC per-polyp sensitivity was 93% (95% CI: 89-97) vs. 97% (95% CI: 94-99) for colonoscopy (P = 0.17). The per-patient sensitivity for the detection of adenomas and carcinomas ≥10 mm was 95% (95% CI: 91-99) for CTC vs. 99% (95% CI: 98-100) for colonoscopy (P = 0.07), while the per-patient specificity was 90% (95% CI: 86-95) and 96% (95% CI: 94-99), respectively (P < 0.001).Conclusion: CTC with limited bowel preparation performed in an FOBT positive screening population has high diagnostic accuracy for the detection of adenomas and carcinomas and a sensitivity similar to that of colonoscopy for relevant lesions. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to derive parameters that predict which high-energy blunt trauma patients should undergo computed tomography (CT) for detection of chest injury.Methods: This observational study prospectively included consecutive patients (>or=16 years old) who underwent multidetector CT of the chest after a high-energy mechanism of blunt trauma in one trauma centre.Results: We included 1,047 patients (median age, 37; 70% male), of whom 508 had chest injuries identified by CT. Using logistic regression, we identified nine predictors of chest injury presence on CT (age >or=55 years, abnormal chest physical examination, altered sensorium, abnormal thoracic spine physical examination, abnormal chest conventional radiography (CR), abnormal thoracic spine CR, abnormal pelvic CR or abdominal ultrasound, base excess <-3 mmol/l and haemoglobin <6 mmol/l). Of 855 patients with >or=1 positive predictors, 484 had injury on CT (95% of all 508 patients with injury). Of all 192 patients with no positive predictor, 24 (13%) had chest injury, of whom 4 (2%) had injuries that were considered clinically relevant.Conclusion: Omission of CT in patients without any positive predictor could reduce imaging frequency by 18%, while most clinically relevant chest injuries remain adequately detected. [ABSTRACT FROM AUTHOR]

The metabolic syndrome (MetS) increases cardiovascular disease (CVD) risk. How MetS increases CVD risk is incompletely understood, but increasing arterial stiffness is one candidate link, which in turn could be explained by (low-grade) inflammation, endothelial dysfunction (ED) or insulin resistance (IR). However, MetS-related increases in stiffness may not be uniformly distributed over muscular and elastic arteries. Therefore, the purpose of this study was to determine: (1) the associations between the MetS, and muscular and elastic arterial stiffness, and (2) whether any such associations could be explained by inflammation, ED or IR. These questions were addressed in the Hoorn Study. MetS was defined according to the NCEP (National Cholesterol Education Program) criteria. Arterial stiffness was determined by ultrasound, tonometry and echocardiography. Inflammation, ED and IR were estimated by C-reactive protein, flow-mediated vasodilation and the homoeostatic model for the assessment of IR, respectively. The results showed that MetS was associated with both femoral and brachial arterial stiffness, significantly so for the distensibility coefficients and for the femoral compliance coefficient. In the carotid artery and aorta, no particular pattern emerged. Additional adjustment for either inflammation, ED or IR did not materially alter the results. The results therefore indicate that muscular arteries may stiffen preferentially over elastic arteries and that distensibility is affected to a greater extent than compliance, thus maintaining volume compliance over vessel wall stiffening. Additionally, the increase in stiffness was not explained by inflammation, ED or IR and suggests that stiffening of the muscular arteries in MetS may not be the consequence of these phenomena. [ABSTRACT FROM AUTHOR]

Mitochondria play an important role in many processes, like glucose metabolism, fatty acid oxidation and ATP synthesis. In this study, we aimed to identify association of common polymorphisms in nuclear-encoded genes involved in mitochondrial protein synthesis and biogenesis with type II diabetes mellitus (T2DM) using a two-stage design. In the first stage, we analyzed 62 tagging single nucleotide polymorphisms (SNPs) in the Hoorn study (n=999 participants) covering all common variation in 13 biological candidate genes. These 13 candidate genes were selected from four clusters regarded essential for correct mitochondrial protein synthesis and biogenesis: aminoacyl tRNA synthetases, translation initiation factors, tRNA modifying enzymes and mitochondrial DNA transcription and replication. SNPs showing evidence for association with T2DM were measured in second stage genotyping (n=10164 participants). After a meta-analysis, only one SNP in SIRT4 (rs2522138) remained significant (P=0.01). Extending the second stage with samples from the Danish Steno Study (n=1220 participants) resulted in a common odds ratio (OR) of 0.92 (0.85–1.00), P=0.06. Moreover, in a large meta-analysis of three genome-wide association studies, this SNP was also not associated with T2DM (P=0.72). In conclusion, we did not find evidence for association of common variants in 13 nuclear-encoded mitochondrial proteins with T2DM.European Journal of Human Genetics (2009) 17, 1056–1062; doi:10.1038/ejhg.2009.4; published online 11 February 2009 [ABSTRACT FROM AUTHOR]

Background/Objective:Early insulin secretion following a meal is representative for normal physiology and may depend on meal composition. To compare the effects of a fat-rich and a carbohydrate-rich mixed meal on insulinogenic index as a measure of early insulin secretion in normoglycemic women (NGM) and in women with type 2 diabetes mellitus (DM2), and to assess the relationship of anthropometric and metabolic factors with insulinogenic index.Subjects/Methods:Postmenopausal women, 76 with NGM and 64 with DM2, received a fat-rich meal and a carbohydrate-rich meal on separate occasions. Early insulin response was estimated as insulinogenic index (△insulin0–30 min/△glucose0−30 min) for each meal. Associations of fasting and postprandial triglycerides, body mass index, waist and hip circumference and alanine aminotransferase with insulinogenic indices were determined.Results:Women with NGM present with higher insulinogenic index than women with DM2. The insulinogenic index following the fat-rich meal (△I30/△G30 (fat)) was higher than the index following the carbohydrate-rich meal (△I30/△G30 (CH)) (P<0.05 in women with DM2, and not significant in women with NGM). In women with DM2, homeostasis model assessment for insulin resistance was positively associated with △I30/△G30 (CH). In women with NGM, waist circumference was independently and inversely associated with △I30/△G30 (fat) and with △I30/△G30 (CH); hip circumference was positively associated with △I30/△G30 (fat).Conclusions:The insulinogenic index following the fat-rich meal was higher than following the isocaloric carbohydrate-rich meal, which might favorably affect postprandial glucose excursions, especially in women with DM2. The association between a larger waist circumference and a lower meal-induced insulinogenic index in women with NGM requires further mechanistic studies.European Journal of Clinical Nutrition (2009) 63, 398–404; doi:10.1038/sj.ejcn.1602953; published online 7 November 2007 [ABSTRACT FROM AUTHOR]

The enzyme hormone-sensitive lipase (HSL) is produced and is active in pancreatic beta cells. Because lipids are known to play a crucial role in normal control of insulin release and in the deterioration of beta cell function, as observed in type 2 diabetes, actions of HSL in beta cells may be critical. This notion has been addressed in different lines of HSL knockout mice with contradictory results. To resolve this, we created a transgenic mouse lacking HSL specifically in beta cells, and characterised this model with regard to glucose metabolism and insulin secretion, using both in vivo and in vitro methods. We found that fasting basal plasma glucose levels were significantly elevated in mice lacking HSL in beta cells. An IVGTT at 12 weeks revealed a blunting of the initial insulin response to glucose with delayed elimination of the sugar. Additionally, arginine-stimulated insulin secretion was markedly diminished in vivo. Investigation of the exocytotic response in single HSL-deficient beta cells showed an impaired response to depolarisation of the plasma membrane. Beta cell mass and islet insulin content were increased, suggesting a compensatory mechanism, by which beta cells lacking HSL strive to maintain normoglycaemia. Based on these results, we suggest that HSL, which is located in close proximity of the secretory granules, may serve as provider of a lipid-derived signal essential for normal insulin secretion. [ABSTRACT FROM AUTHOR]

Objective:A high monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) intake is associated with lower plasma low-density lipoprotein (LDL)-cholesterol. However, PUFA may increase the susceptibility of LDL to undergo oxidative modifications. The aim of this study was to analyze the association of habitual dietary fat intake with LDL size and oxidizability.Design:Cross-sectional.Setting:Cohort study.Subjects:Seven hundred and fifty-eight subjects with normal, impaired glucose metabolism and type II diabetes.Interventions:Mean LDL size was measured by high-performance gel-filtration chromatography. In vitro oxidizability of LDL was determined by measuring lag time, reflecting the resistance of LDL to copper-induced oxidation. Information about dietary fat intake was obtained by a validated food frequency questionnaire.Results:PUFA intake (energy percent) was significantly and negatively associated with LDL size in subjects with type II diabetes (standardized beta (95% confidence interval) −0.17 (−0.28;−0.06)) and impaired glucose metabolism – although not statistically significant – (−0.09 (−0.24;0.05)), but not in subjects with normal glucose metabolism (0.01 (−0.10;0.12)) (P-value for interaction=0.02). No significant associations were observed for total, saturated fat and MUFA intake with LDL size. Intake of fat was associated with lag time; however, the small magnitude of the associations suggested that the composition of dietary fat is not a major factor affecting lag time. The same association with lag time was observed in all three glucose metabolism categories.Conclusions:In individuals with abnormal glucose metabolism, higher PUFA intake is associated with smaller LDL particle size, but does not alter the susceptibility of LDL to in vitro oxidation.Sponsorship:Dutch Diabetes Research Foundation, and the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO).European Journal of Clinical Nutrition (2007) 61, 205–211. doi:10.1038/sj.ejcn.1602492; published online 30 August 2006 [ABSTRACT FROM AUTHOR]

Recently, a new oral liver-specific manganese-based MR agent (CMC-001) has been introduced. This contrast medium is delivered to the liver in high concentrations in the portal vein and very low doses in the hepatic artery, as only small amounts of manganese enter the general circulation. It is taken up by the hepatocytes and excreted in the bile. Our initial experience with the new MR contrast medium in a variety of patients is reported. A total of 20 patients (11 males and 9 females) were studied with MR imaging 2 h after oral ingestion of the contrast agent. Sixteen patients were referred for evaluation of focal liver lesion(s), whereas in the remaining four patients, evaluation of the biliary tract was requested. In the 17 patients without biliary obstruction, there was an increased signal intensity of the liver parenchyma, whereas in the three patients with biliary obstruction, the uptake was delayed. There was excellent visualization of the biliary system on the T1-weighted images in the 16 patients without biliary obstruction referred for evaluation of a focal liver lesion. In seven patients, the uptake was patchy. In patients with focal liver lesions or biliary tract diseases, it is possible to increase the signal intensity of the liver parenchyma after the oral intake of CMC-001. In patients without biliary tract obstruction, the biliary system is easily visualized. Oral manganese seems to be useful in hepatobiliary MRI. Further research is strongly warranted. [ABSTRACT FROM AUTHOR]

The association between depression and insulin resistance has been investigated in only a few studies, with contradictory results reported. The aim of this study was to determine whether the association between symptoms of depression and insulin resistance varies across glucose tolerance status and between men and women. Cross-sectional data from a population-based cohort study in Hoorn, a medium-sized town in the Netherlands, were analysed. The study sample consisted of 541 men and women aged 55–75 years, of whom 260 had NGT, 164 had IGT and 117 had established type 2 diabetes mellitus. Main outcome measures were insulin resistance defined by the homeostasis model assessment for insulin resistance (HOMA-IR) and symptoms of depression using the Centre for Epidemiologic Studies Depression Scale (CES-D). In the total sample, we found a weak positive correlation between the depressive symptoms CED-D scores and HOMA-IR scores ( r s = 0.156, p < 0.001). Even weaker associations were found in subjects with NGT ( r s = 0.041, p=0.509), in subjects with IGT ( r s = 0.112, p = 0.160) and in subjects with type 2 diabetes ( r s = 0.007, p = 0.942). The association between depressive symptoms and insulin resistance was similar for men and women. We found only weak associations between depressive symptoms and insulin resistance, which did not differ among different glucose metabolism subgroups or between men and women. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: This systematic review examines the relationship between alcohol consumption and long-term complications of type 2 diabetes. Meta-analyses could only be performed for total mortality, mortality from CHD, and CHD incidence, because the availability of articles on other complications was too limited. Materials and methods: A PubMed search through to September 2005 was performed and the reference lists of relevant articles examined. Among the relevant articles there were six cohort studies reporting on the risk of total mortality and/or fatal and/or incident CHD in alcohol non-consumers and in at least two groups of alcohol consumers. Results: Statistical pooling showed lower risks in alcohol consumers than in non-consumers (the reference category). The relative risk (RR) of total mortality was 0.64 (95% CI 0.49–0.82) in the <6 g/day category. In the higher alcohol consumption categories (6 to <18, and ≥18 g/day), the RRs of total mortality were not significant. Risks of fatal and total CHD were significantly lower in all three categories of alcohol consumers (<6, 6 to <18 and ≥18 g/day) than in non-consumers, with RRs ranging from 0.34 to 0.75. Conclusions/interpretation: This meta-analysis shows that, as with findings in the general population, moderate alcohol consumption is associated with a lower risk of mortality and CHD in type 2 diabetic populations. [ABSTRACT FROM AUTHOR]

Objective: To determine the level of diabetes-related symptom distress and its association with negative mood in subjects participating in a targeted population-screening program, comparing those identified as having type 2 diabetes vs. those who did not.Research Design and Methods: This study was conducted within the framework of a targeted screening project for type 2 diabetes in a general Dutch population (age 50-75 years). The study sample consisted of 246 subjects, pre-selected on the basis of a high-risk profile; 116 of whom were subsequently identified as having type 2 diabetes, and 130 who were non-diabetic subjects. Diabetes-related symptom distress and negative mood was assessed approximately 2 weeks, 6 months, and 12 months after the diagnosis of type 2 diabetes, with the Type 2 Diabetes Symptom Checklist and the Negative well-being sub scale of the Well-being Questionnaire (W-BQ12), respectively.Results: Screening-detected diabetic patients reported significantly greater burden of hyperglycemic (F = 6.0, df = 1, p = 0.015) and of fatigue (F = 5.3, df = 1, p = 0.023) symptoms in the first year following diagnosis type 2 diabetes compared to non-diabetic subjects. These outcomes did not change over time. The total symptom distress (range 0-4) was relatively low for both screening-detected diabetic patients (median at approximately 2 weeks, 6 months, and 12 months; 0.24, 0.24, 0.29) and non-diabetic subjects (0.15, 0.15, 0.18), and not significantly different. No average difference and change over time in negative well-being was found between screening-detected diabetic patients and non-diabetic subjects. Negative well-being was significantly positive related with the total symptom distress score (regression coefficient beta = 2.86, 95% CI 2.15-3.58).Conclusions: The screening-detected diabetic patients were bothered more by symptoms of hyperglycemia and fatigue in the first year following diagnosis type 2 diabetes than non-diabetic subjects. More symptom distress is associated with increased negative mood in both screening-detected diabetic patients and non-diabetic subjects. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The exact pathogenesis of retinopathy in diabetic and non-diabetic individuals is incompletely understood, but may involve chronic low-grade inflammation and dysfunction of the vascular endothelium. The aim of this study was to investigate the association of inflammation and endothelial dysfunction with prevalent retinopathy in individuals with and without type 2 diabetes. Methods: As part of a population-based cohort study, 625 individuals aged 50-74 years, stratified according to age, sex and glucose tolerance status, underwent an extensive physical examination. Retinopathy was assessed by an ophthalmological examination, including funduscopy and two-field 45° fundus photography with mydriasis in both eyes. Levels of C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), von Willebrand factor, and soluble vascular adhesion molecule-1 (sVCAM-1) were assessed, together with the urinary albumin : creatinine ratio, and the results were combined to obtain summarising z scores for inflammation and endothelial dysfunction. Results: The prevalence of retinopathy was positively associated with tertiles of CRP and sICAM-1. When compared with the lowest tertile, the highest tertile of the inflammatory z score was associated with retinopathy in all subjects (odds ratio [OR]=2.2, 95% CI 1.2-4.1, adjusted for age, sex and glucose tolerance status). The highest fertile of the endothelial dysfunction z score was associated with retinopathy among diabetic individuals (OR=4.4, 95% CI 1.2-15.9, adjusted for age and sex) but not in non-diabetic individuals. Additional adjustment for other risk factors, such as systolic and diastolic blood pressure, BMI, total cholesterol and triglycerides, or mutual adjustment of the inflammatory and endothelial dysfunction z scores did not change the results. Conclusions/interpretation: In this study, inflammatory activity and endothelial dysfunction were associated with retinopathy, which suggests their involvement in the pathogenesis of retinopathy. [ABSTRACT FROM AUTHOR]