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Many proteins, especially eukaryotic proteins, membrane proteins and protein complexes, are challenging to study because they are difficult to purify in their native state without disrupting the interactions with their partners. Hence, our lab developed a novel purification technique employing Nanobodies® (Nbs). This technique, called nanobody exchange chromatography (NANEX), utilises an immobilised low-affinity Nb to capture the target protein, which is subsequently eluted – along with its interaction partners – by introducing a high-affinity Nb. In line with the growing trend towards studying proteins in smaller sample sizes, the present study validates miniaturisation of NANEX in a packed bed microfluidic (μNANEX) chip. This μNANEX setup integrates up to five submicroliter silicon chips, enabling fully automated and reproducible purifications within minutes. Additionally, a digital twin model of the μNANEX column, which accurately predicts the effect of the reaction kinetics and mass transfer on the elution peaks, has been validated over a broad range of experimental conditions. The effectiveness of the method is demonstrated with Nbs binding to the green fluorescent protein (GFP), allowing streamlined purification of any GFP fusion protein from biological samples. Specifically, we used μNANEX to purify 0.1–1 μg of GFP-fused yeast proteins from 20 μL crude lysate and identified their interaction partners via mass spectrometry, showing that μNANEX purification preserves protein complexes. [ABSTRACT FROM AUTHOR]

From a theoretical perspective of project-based organising, this study analyses how a deployed military task force heuristically learns. Empirically, learning within Task Force Uruzgan (TFU) in southern Afghanistan, is scrutinised. This contribution of the Netherlands armed forces to NATO's International Security Assistance Force (ISAF) lasted for four years and saw successive rotations of task forces simultaneously fighting an insurgency and trying to stabilise a part of Afghanistan through reconstruction and development projects. Above all, the study has found that task ambiguity can make it challenging for a task force deployed to deal with varying contingencies at the same time. Two effects are noteworthy. First, learning can become compartmentalised, with different organisational elements following their own learning trajectories. Second, learning can also become short-term focused, responding to the most imminent and familiar threat. Combined, both learning impulses affect organisational coherence in meeting the overarching mission end state. [ABSTRACT FROM AUTHOR]

Reentry, the most common cause of severe arrhythmias, is initiated by slow conduction and conduction block. Hence, evaluating conduction velocity and conduction block is of primary importance. However, the assessment of cardiac conduction safety in experimental and clinical settings remains elusive. To identify markers of conduction instability that can be determined experimentally, we developed an approach based on new pacing paradigms. Conduction across a cardiac tissue expansion was assessed in computer simulations and in experiments using cultures of neonatal murine cardiomyocytes on microelectrode arrays. Simulated and in vitro tissues were paced at a progressively increasing rate, with stochastic or alternating variations of cycle length, until conduction block occurred. Increasing pacing rate led to conduction block near the expansion. When stochastic or alternating variations were introduced into the pacing protocol, the standard deviation and the amplitude of alternating variations of local conduction times emerged as markers of unstable conduction prone to block. In both simulations and experiments, conduction delays were prolonged at the expansion but increased only slightly during the pacing protocol. In contrast, these markers of instability increased several-fold, early before block occurrence. The first and second moments of these two metrics provided an estimation of the site of block and the accuracy of this estimation. Therefore, when beat-to-beat variations of pacing cycle length are introduced into a pacing protocol, the local variability of conduction permits to predict sites of block. Our pacing paradigms may have translational applications in clinical cardiac electrophysiology, particularly in identifying ablation targets during mapping procedures. [Display omitted] • Functional conduction block can precipitate severe reentrant arrhythmias. • Conduction across a current-to-load mismatch was studied in silico and in vitro. • Pacing with stochastic or alternating intervals was used to destabilize conduction. • The local variability of conduction times permitted to anticipate the site of block. • Our new pacing paradigms thus open avenues for basic and translational applications. [ABSTRACT FROM AUTHOR]

The article discusses the themes of disincorporation and the people's two bodies in the works of José Saramago, focusing on the novels "Blindness" and "Death at Intervals." It explores how Saramago's fiction engages with the relationship between bodies, language, and things, challenging traditional notions of power and sovereignty. The text delves into the complexities of embodiment, symbolization, and the political imagination, drawing on the perspectives of thinkers like Jacques Rancière and Claude Lefort. The analysis also connects Saramago's work to contemporary issues, such as the Covid-19 pandemic, highlighting the potential for new forms of community and resistance in post-pandemic times. [Extracted from the article]

The article "Literature and Public World-Making: Introduction" explores the intersection of literature and public spheres, focusing on the global solidarity movement for Palestinian liberation. It discusses the commemorative makeshift infrastructure named after literary authors, such as Walid Daqqa and Refaat Alareer, as part of protest movements. The text delves into the transformative potential of literature in shaping counterpublics and public world-making, emphasizing the importance of critical engagement with fictionality in responding to contemporary challenges. The essays in the issue examine various dimensions of publicness, including corporeality, literary reception, illiberalism, and the poetics of the sea, to explore how literature contributes to critical, emancipatory interventions in public spheres. [Extracted from the article]

Where and what we attend is very much determined by what we have encountered in the past. Recent studies have shown that people learn to extract statistical regularities in the environment resulting in attentional suppression of locations that were likely to contain a distractor, effectively reducing the amount of attentional capture. Here, we asked whether this suppression effect due to statistical learning is dependent on the specific configuration within which it was learned. The current study employed the additional singleton paradigm using search arrays that had a configuration consisting of set sizes of either four or 10 items. Each configuration contained its own high probability distractor location. If learning would generalize across set size configurations, both high probability locations would be suppressed equally, regardless of set size. However, if learning to suppress is dependent on the configuration within which it was learned, one would expect only suppression of the high probability location that matched the configuration within which it was learned. The results show the latter, suggesting that implicitly learned suppression is configuration-dependent. Thus, we conclude that the high probability location is learned within the configuration context within which it is presented. [ABSTRACT FROM AUTHOR]

Through statistical learning, humans can learn to suppress visual areas that often contain distractors. Recent findings suggest that this form of learned suppression is insensitive to context, putting into question its real-life relevance. The current study presents a different picture: we show context-dependent learning of distractor-based regularities. Unlike previous studies which typically used background cues to differentiate contexts, the current study manipulated task context. Specifically, the task alternated from block to block between a compound search and a detection task. In both tasks, participants searched for a unique shape, while ignoring a uniquely colored distractor item. Crucially, a different high-probability distractor location was assigned to each task context in the training blocks, and all distractor locations were made equiprobable in the testing blocks. In a control experiment, participants only performed a compound search task such that the contexts were made indistinguishable, but the high-probability locations changed in exactly the same way as in the main experiment. We analyzed response times for different distractor locations and show that participants can learn to suppress a location in a context-dependent way, but suppression from previous task contexts lingers unless a new high-probability location is introduced. [ABSTRACT FROM AUTHOR]

Background: The Dutch population-based cervical cancer screening programme (PBS) consists of primary high-risk human papilloma virus (hrHPV) testing with cytology as triage test. In addition to cervical scraping by a general practitioner (GP), women are offered self-sampling to increase participation. Because cytological examination on self-sampled material is not feasible, collection of cervical samples from hrHPV-positive women by a GP is required. This study aims to design a methylation marker panel to detect CIN3 or worse (CIN3+) in hrHPV-positive self-samples from the Dutch PBS as an alternative triage test for cytology. Methods: Fifteen individual host DNA methylation markers with high sensitivity and specificity for CIN3+ were selected from literature and analysed using quantitative methylation-specific PCR (QMSP) on DNA from hrHPV-positive self-samples from 208 women with CIN2 or less (< CIN2) and 96 women with CIN3+. Diagnostic performance was determined by area under the curve (AUC) of receiver operating characteristic (ROC) analysis. Self-samples were divided into a train and test set. Hierarchical clustering analysis to identify input methylation markers, followed by model-based recursive partitioning and robustness analysis to construct a predictive model, was applied to design the best marker panel. Results: QMSP analysis of the 15 individual methylation markers showed discriminative DNA methylation levels between < CIN2 and CIN3+ for all markers (p < 0.05). The diagnostic performance analysis for CIN3+ showed an AUC of ≥ 0.7 (p < 0.001) for nine markers. Hierarchical clustering analysis resulted in seven clusters with methylation markers with similar methylation patterns (Spearman correlation> 0.5). Decision tree modeling revealed the best and most robust panel to contain ANKRD18CP, LHX8 and EPB41L3 with an AUC of 0.83 in the training set and 0.84 in the test set. Sensitivity to detect CIN3+ was 82% in the training set and 84% in the test set, with a specificity of 74% and 71%, respectively. Furthermore, all cancer cases (n = 5) were identified. Conclusion: The combination of ANKRD18CP, LHX8 and EPB41L3 revealed good diagnostic performance in real-life self-sampled material. This panel shows clinical applicability to replace cytology in women using self-sampling in the Dutch PBS programme and avoids the extra GP visit after a hrHPV-positive self-sampling test. [ABSTRACT FROM AUTHOR]

In an auditory statistical learning paradigm, listeners learn to partition a continuous stream of syllables by discovering the repeating syllable patterns that constitute the speech stream. Here, we ask whether auditory statistical learning benefits from spaced exposure compared with massed exposure. In a longitudinal online study on Prolific, we exposed 100 participants to the regularities in a spaced way (i.e., with exposure blocks spread out over 3 days) and another 100 in a massed way (i.e., with all exposure blocks lumped together on a single day). In the exposure phase, participants listened to streams composed of pairs while responding to a target syllable. The spaced and massed groups exhibited equal learning during exposure, as indicated by a comparable response-time advantage for predictable target syllables. However, in terms of resulting long-term knowledge, we observed a benefit from spaced exposure. Following a 2-week delay period, we tested participants’ knowledge of the pairs in a forced-choice test. While both groups performed above chance, the spaced group had higher accuracy. Our findings speak to the importance of the timing of exposure to structured input and also for statistical learning outside of the laboratory (e.g., in language development), and imply that current investigations of auditory statistical learning likely underestimate human statistical learning abilities. [ABSTRACT FROM AUTHOR]

The present experiment aimed to identify the potential protective role of empagliflozin (EMPA) on haloperidol (HAL)-induced ovarian damage in female rats because of its anti-inflammatory, antioxidant, and antiapoptotic effects. EMPA was administered in the presence and absence of HAL. Thirty-two adult female albino rats were divided into four groups. Control group, EMPA group: received EMPA (10 mg/kg/day) p.o., HAL group: received HAL (2 mg/kg/day) p.o., HAL + EMPA group: HAL (2 mg/kg/day) combined with EMPA for 28 days. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-mullerian hormone (AMH) levels were measured. Ovarian oxidative stress parameters, besides inflammatory and apoptotic biomarkers, and ovarian Sirtuin-1 (Sirt-1) were evaluated. Ovarian histopathological examination and heat shock protein 70 (Hsp70) immunohistochemical study were performed. HAL significantly increased serum levels of FSH, LH, and ovarian inflammatory, apoptotic, and oxidative stress biomarkers and decreased serum AMH levels and Sirt-1 expression. Histopathological findings of ovarian damage and high Hsp70 immunoexpression were detected. EMPA significantly normalized the distributed hormonal levels, oxidative stress, inflammatory, and apoptotic biomarkers with a prompt improvement in the histopathological picture and a decrease in Hsp70 immunoexpression. Accordingly, EMPA protected against HAL-induced ovarian toxicity by modulating the Sirt-1/Hsp70/TNF-α/caspase-3 signaling pathway. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the diagnostic and prognostic value of non-hyperaemic Pd/Pa and to determine its additional value when combined with the gold standard hyperaemic pressure ratio (FFR) to guide revascularization. In a large, multi-center, retrospective registry, we included a total of 2141 patients with a clinical indication for coronary angiography providing physiological data in 2726 vessels. A classification was made based on the FFR (cut-off value: 0.80) and non-hyperaemic Pd/Pa (cut-off value: 0.92) values and the primary outcome was target-vessel failure (TVF) at 5-year follow-up. Mean age was 63 ± 10.0 and 75% of the study population were men. Regression analysis showed an overall good correlation between FFR and non-hyperaemic Pd/Pa (r = 0.73, p < 0.005) and discordance was present in 17% of the vessels. Resting Pd/Pa was independently associated with TVF at 5-year follow-up (HR 0.08, 95%CI: 0.02–0.27; p < 0.005). The risk for TVF was the lowest in vessles with concordant normal pressure ratio's, with the highest risk in vessels with any abnormal pressure ratio in which revascularization was deferred. In these vessels, there was no difference in risk for TVF between the discordant and concordant abnormal values. Abnormal pressure ratios in both non-hyperemic and hyperemic conditions portend important prognostic value. Combined application of FFR and non-hyperemic Pd/Pa efficiently identifies those vessels with concordant normal resting and hyperemic pressure ratios of which long-term clinical outcomes are excellent. These data lead to hypothesize that the decision to defer revascularization should potentially be based on combined non-hyperemic and hyperemic pressure ratios. Inclusive Invasive Physiological Assessment in Angina Syndromes Registry (ILIAS Registry), NCT04485234 • Abnormal pressure ratios in both non-hyperemic and hyperemic conditions portend important prognostic value for TVF at 5-year follow up. • Combined application of FFR and non-hyperemic Pd/Pa efficiently identifies those vessels with concordant normal resting and hyperemic pressure ratios of which long-term clinical outcomes are excellent. • Our data leads to hypothesize that the decision to defer revascularization should potentially be based on combined non-hyperemic and hyperemic pressure ratios, but require confirmation in prospective studies. [ABSTRACT FROM AUTHOR]

Morbid obesity and prolonged pregnancy are independently associated with adverse delivery and perinatal outcomes. We conducted a retrospective observational study on otherwise uncomplicated women with a body mass index (BMI) ≥ 40 kg/m2 where, having reached term, induction of labour (IOL) was planned, to prevent prolonged pregnancy. The primary aim was to describe delivery outcomes and short-term maternal and perinatal adverse events. Of 117 cases included, 69 (59%) laboured spontaneously before the induction date, while 48 (41%) required an IOL. Of 48 patients that underwent an IOL, 22 (45.8%) achieved vaginal delivery, compared to 55 (79.7%) who laboured spontaneously (p = <.001). Twenty-two (18.8%) of the 117 babies weighed more than 4000 g, with 13 of these delivered vaginally. Overall, term patients with morbid obesity who laboured spontaneously before requiring induction, had a high rate of vaginal delivery. However, when IOL was required, the rate of caesarean delivery rose dramatically. What is already known on this subject? Morbid obesity and prolonged pregnancy are independently associated with adverse delivery and perinatal outcomes. Induction of labour (IOL) increases the workload in busy units. What do the results of this study add? These results help inform accurate counselling on delivery outcomes, which is integral to respectful care, for the continuously increasing numbers of morbidly obese pregnant women. What the implications are of these findings for clinical practice and/or further research? It is preferable to avoid semi- or urgent caesarean deliveries in morbidly obese women after IOL. The outcomes of earlier induction of labour from 39- or 40-weeks' gestation requires investigation. Earlier induction may reduce the numbers of caesarean deliveries for abnormal cardiotocograph during the process. [ABSTRACT FROM AUTHOR]

The purpose of this study was to verify whether pre-treatment digital setups can accurately predict the tooth positions after presurgical orthodontic treatment has been performed in a 3-dimensional way. Twenty-six patients who underwent a combined orthodontic-orthognathic surgical treatment were included. Pre-treatment digital dental models were merged with cone beam computed tomography (CBCT) scans. One operator fabricated virtual setups to simulate the tooth movements of the presurgical orthodontic treatment. Prior to surgery, digital dental models were merged with the CBCT scans. Differences between de virtual setups and the presurgical dental models were calculated using linear mixed model analyses. Differences in tooth displacements exceeding the boundaries of clinical acceptance (>2 degrees for rotations and >0.6 mm for translations) were found in 75% of the rotational and 52% of translational mean differences in the maxilla and in 74% of the rotational mean differences and 44% of the translational mean differences in the mandible. Significant differences were found for all tooth types and in all tooth displacement directions with significant effects of extractions and surgically assisted rapid maxillary expansion (SARME) procedures. The accuracy of the digital setup is still too limited to correctly simulate the presurgical orthodontic treatment. [ABSTRACT FROM AUTHOR]

Background and Purpose: Protoxin II (ProTx II) is a high affinity gating modifier that is thought to selectively block the Nav 1.7 voltage-dependent Na+ channel, a major therapeutic target for the control of pain. We aimed at producing ProTx II analogues entitled with novel functionalities for cell distribution studies and biochemical characterization of its Nav channel targets.Experimental Approach: We took advantage of the high affinity properties of the peptide, combined to its slow off rate, to design a number of new tagged analogues useful for imaging and biochemistry purposes. We used high-throughput automated patch-clamp to identify the analogues best matching the native properties of ProTx II and validated them on various Nav -expressing cells in pull-down and cell distribution studies.Key Results: Two of the produced ProTx II analogues, Biot-ProTx II and ATTO488-ProTx II, best emulate the pharmacological properties of unlabelled ProTx II, whereas other analogues remain high affinity blockers of Nav 1.7. The biotinylated version of ProTx II efficiently works for the pull-down of several Nav isoforms tested in a concentration-dependent manner, whereas the fluorescent ATTO488-ProTx II specifically labels the Nav 1.7 channel over other Nav isoforms tested in various experimental conditions.Conclusions and Implications: The properties of these ProTx II analogues as tools for Nav channel purification and cell distribution studies pave the way for a better understanding of ProTx II channel receptors in pain and their pathophysiological implications in sensory neuronal processing. The new fluorescent ProTx II should also be useful in the design of new drug screening strategies. [ABSTRACT FROM AUTHOR]

[Display omitted] • We present a 3D framework to evaluate peatland degradation research. • 54 % of 115 analyzed studies assess vegetation using space- or airborne optical data. • Research addressing vegetation, peat and hydrology in a tripartite system is rare. • Combined remote sensing sources allow more holistic peatland degradation research. Peatland degradation causes a number of environmental problems ranging from greenhouse gas (GHG) emissions to subsidence and ecosystem loss. Degraded peatlands, covering just 0.3 % of Earth's land area (500,000 km2), disproportionately contribute 5 % of GHG emissions, exacerbating the climate crisis. Once degraded, restoring peatland ecosystem functions often presents a considerable challenge because degradation affects several interconnected components in peatlands: the peat body, hydrology, and vegetation. The planning and implementation of effective peatland restoration strategies requires the accurate mapping of degradation. This review examines how remote sensing has been used to examine the components of peatland degradation. A conceptual 3D space was created using the three components of peat, hydrology, and vegetation. Within this three-dimensional space, five groups of studies were identified, representing each one of the three dimensions individually, or addressing two or three of them simultaneously. Of 115 relevant articles, 54 % solely addressed vegetation degradation, 18 % evaluated two dimensions equally, while just 10 % of all studies examined all three dimensions. These results highlight a lack of remote sensing-based research that considers all aspects of peatland degradation and their interdependence simultaneously. By synthesizing our findings into three descriptive peatland degradation scenarios (a boreal landscape, a temperate large peatland complex and a temperate small raised bog), we present rapid and efficient methods and resources for a more holistic approach to degradation mapping and monitoring. Consequently, such comprehensive assessments integrating different historical and current remote sensing data should be carried out more frequently. They allow the visualization of ecological consequences of peatland degradation and promote peatland restoration in all parts of these tripartite ecosystems. [ABSTRACT FROM AUTHOR]

A retrospective observational study of new patients who visited the gynaecology outpatient clinic at Tygerberg Hospital, South Africa, between February and June 2019 was conducted to determine the association between body mass index (BMI) and gynaecological disorders. BMI was calculated and analysed concerning the presenting complaint and final diagnosis. From the sample of 651 patients, 18.4% had a normal BMI and 47.3% were classified as overweight or obese class 1. Older age was associated with a higher BMI (p =.013). Hypertension was most prevalent (26.7%) and associated with excess weight (p <.001). Disorders significantly associated with obesity were infertility (odds ratio [OR] 1.013, 95% confidence interval [CI] 0.992–1.033, p =.001), polycystic ovarian syndrome (OR 1.058, 95% CI 1.028–1.089, p =.006), pelvic organ prolapse (OR 1.027, 95% CI 0.995–1.060, p =.0291) and postmenopausal bleeding (OR 1.038, 95% CI 1.009–1.068, p =.048). Chronic pelvic pain and endometriosis were associated with a low BMI. What is already known on this subject? It is well known that obesity has multiple negative effects on health. It affects women's health on many levels including their endocrine balance as well as pressure effects on the pelvic floor. The association between gynaecological disorders and excess weight has been described mainly in the context of separate gynaecological conditions. What the results of study add? This study described the large numbers of women with obesity in the South African context. It adds to the body of knowledge by looking at the association of BMI, not only obesity, and a large range of the most seen gynaecological conditions in the study setting. What the implications are of these findings for clinical practice and/or further research? This study highlights the importance of lifestyle and nutritional implications on women's health. For clinical practice, this knowledge needs to be applied with every opportunity to counsel women on how their weight can affect their gynaecological health. The focus of further research should focus on the most effective strategies to combat obesity in a holistic patient-centered approach. [ABSTRACT FROM AUTHOR]

Diagnosis and treatment of active tuberculosis (ATB) as well as latent tuberculosis infection (LTBI) are required for effective tuberculosis (TB) control, especially in TB endemic area. The usefulness of conventional tests to distinguish between ATB and LTBI has remained challenging. The present study was aimed to demonstrate the usefulness of the serological response to synthetic peptides from Mycobacterium tuberculosis (Mtb) antigens for discrimination between ATB and LTBI in Warao Amerindians. Serum IgG antibody levels were measured by the indirect ELISA assay using 22 designed and synthesized peptides derived from immunogenic Mtb ESAT-6 and Ag85A proteins. A total of 211 adult Warao Amerindians were included; cases with active TB (ATB, n = 75), latent TB infection (LTBI, n = 85) and non-infected (NI, n = 51). The approach’s diagnostic information was compared using receiver operating characteristic (ROC) curves. For ATB diagnostic performance between ATB and NI; ESAT-6; P-12037 had 100% of sensitivity (AUC = 0.812; 0.733 to 0.891 95% CI); and Ag85A; P-10997 had 100% of specificity (AUC = 0.691; 0.597 to 0.785 95% CI); and ATB and LTBI; Ag85A; P-29878 had 100% of sensitivity (AUC = 0.741; 0.666–0.817 95% CI), and P-29879 had 99% of specificity (AUC = 0.679; 0.593–0.765 95% CI). While that ESAT-6 P-12037 also allowed differentiation between LTBI and NI or healthy ones. It had 98.8% of sensitivity and 98.0% of specificity (AUC = 0.640; 0.545–0.735 95% CI). The potential of combination-antigen immunoassays with peptides could discriminate between Warao Amerindians with ATB, LTBI and NI. Further validation of this approach could lead to developing a complementary tool for rapid diagnosis of TB infections. [ABSTRACT FROM AUTHOR]

Purpose: This study explores the effect of glaucomatous visual field defects on several neuropsychological tests that are often used in research and in clinical settings. Methods: Nineteen glaucoma patients and nineteen healthy participants, which are current drivers and older than 65 years old were included. All participants completed the Montreal Cognitive Assessment (MoCA), the Trail Making Test (TMT), the Benton Visual Retention Test (BVRT), the Snellgrove Maze Task (SMT) and the Digit Span Test (DST). All participants were also tested on contrast sensitivity and near and far visual acuity. For the glaucoma patients, visual field tests were downloaded from hospital servers. Results: On the MoCA test, glaucoma patients scored lower than the healthy group, but not significantly. On the MoCA‐Blind, the difference was statistically significant. Glaucoma patients also had lower percentile scores on the TMT, with a significant difference in the TMT‐A, but this difference largely disappeared in the calculated TMT B‐A index, which isolates the cognitive component. The BVRT and SMT showed no significant differences between both groups. In the only non‐visual test, the DST, glaucoma patients outperformed the healthy group. Glaucoma severity did not influence results, except for the BVRT on which the moderate/severe group has better scores. Conclusion: Using visual items might lead to conclusions about cognition when it should be one about vision. Therefore, careful selection of tests is needed when examining cognition in glaucoma patients. [ABSTRACT FROM AUTHOR]

Voltage-gated calcium channels are essential regulators of brain function where they support depolarization-induced calcium entry into neurons. They consist of a pore-forming subunit (Cavα1) that requires co-assembly with ancillary subunits to ensure proper functioning of the channel. Among these ancillary subunits, the Cavβ plays an essential role in regulating surface expression and gating of the channels. This regulation requires the direct binding of Cavβ onto Cavα1 and is mediated by the alpha interacting domain (AID) within the Cavα1 subunit and the α binding pocket (ABP) within the Cavβ subunit. However, additional interactions between Cavα1 and Cavβ have been proposed. In this study, we analyzed the importance of Cavβ3 surface charged residues in the regulation of Cav2.1 channels. Using alanine-scanning mutagenesis combined with electrophysiological recordings we identified several amino acids within the Cavβ3 subunit that contribute to the gating of the channel. These findings add to the notion that additional contacts besides the main AID/ABP interaction may occur to fine-tune the expression and properties of the channel. [ABSTRACT FROM AUTHOR]

Bariatric surgery is the most effective treatment for obesity and improves several manifestations of the metabolic syndrome, including nonalcoholic fatty liver disease. Strict nutritional counseling after bariatric surgery is a key in realizing these outcomes. When postoperative nutrient intake or nutrient uptake is compromised, bariatric surgery can also lead to severe hepatic complications. Here, we describe 3 cases of acute liver injury and acute liver failure caused by bariatric surgery, all with different management strategies and outcomes. [ABSTRACT FROM AUTHOR]

If there is one certainty for the sustainable management of water resources is that facing uncertainty is an unavoidable matter. A concern that, in addition to the best available scientific knowledge and models, requires deep insights about the socio relational processes that underlie decision-making. Our objective here is to better understand if and how the socio relational environment in which decisions are made shapes decision-making under uncertainty in common pool water resource management. Our goal is twofold: methodological and analytical. It consists in designing experiments for carrying out uncertainty analysis to explore the influence that the relationships established among decision actors have in making decision choices under uncertainty in management processes. To this end, we developed one experimental game protocol, representing a typical water management scenario: irrigation, which we use to test two different conjectures about the combined effects of uncertainty and relationships. In doing so, we play close attention to the quality of relationships developed among players (acting as water managers), and how these relationships are structured and organized. Initial tests confirmed the importance that the relationships established among players have for coping with uncertainty in managing water resources. [ABSTRACT FROM AUTHOR]

Background and purpose: The consensus that bone stock preservation and optimal restoration of offset and leg length is important in total hip arthroplasty is now widespread, especially for young and active patients. Short stems seem promising in this aspect, though implant stability is still of concern. This study looked at the migration pattern of the Optimys short stem through RSA analysis. Patients and methods: 40 patients were included. RSA images were made directly postoperatively (within 5 days), at 6 weeks and at 3, 6, 12 and 24 months. Double examinations were made for precision measurement. HOOS and pain scores were obtained preoperatively and at 2 years. 4 patients were excluded due to protocol violation and 1 patient was excluded for RSA analysis with a CN number >110. 2 patients were lost to follow-up after 3 and 6 months (n = 1 lost, n = 1 deep infection, respectively). Results: Mean age was 60 years with a mean BMI of 27. RSA analysis of 34 patients showed a significant initial median proximodistal translation (subsidence) of 0.21 mm (IQR 0.64–0.06) and anteversion-retroversion rotation of 0.59° (IQR 0.01–1.34) at 6 weeks, after which the stem stabilises and showed no further significant movement. Median migration in other directions was small. 4 patients had an initial subsidence of >2 mm, all showed secondary stabilisation. HOOS outcomes were satisfactory, with the domain symptoms and pain showing a median score of 95/100 at 2 years. Conclusions: After initial migration the Optimys achieves secondary stabilisation, suggesting low risk on long-term aseptic loosening. Clinical trials registration: NL47055.048.13. [ABSTRACT FROM AUTHOR]

Postoperative follow-up with a primary care practitioner is critical to evaluate ongoing diabetic control and treatment, preferably targeting a glycosylated hemoglobin level of <= 7%, as per the Diabetes Canada Clinical Practice Guidelines.[35] Gastrointestinal bleeding Gastrointestinal bleeding is an uncommon but important consideration in patients who have undergone cardiac surgery, especially if they have pre-existing gastrointestinal pathology. Recent data suggest that almost 10% of patients who undergo coronary artery bypass grafting (CABG) are readmitted to hospital within 30 days of surgery. Patients may also be discharged on anticoagulation, specifically warfarin if their atrial fibrillation persists for more than 48 hours, to decrease their risk of stroke.[37] New-onset atrial fibrillation after CABG is self-limiting, and almost all patients return to a normal sinus rhythm by 6-12 weeks after cardiac surgery.[36],[38],[39] Therefore, primary care practitioners following such patients should always re-evaluate whether anticoagulant treatment is still necessary by 3 months postoperatively.[36],[39] Discontinuation of anticoagulation should be considered at this time if the patient is arrhythmia free (normal sinus rhythm, no palpitations) and the only instance of atrial fibrillation was after cardiac surgery.[36],[39] How should hypertension be managed after CABG surgery? Most CABG surgeries are performed using cardiopulmonary bypass, which uniquely affects patients' physiology and leads to specific postoperative complications in some patients. [Extracted from the article]

Jeremiah 52 largely parallels 2 Kgs 25, and Jer 40–43 contains various sentences that are also found in 2 Kgs 25:22–26. The present article compares these parallel texts, in order to determine the relationship between the Masoretic text of Jeremiah and the book's Old Greek translation. It concludes that this relationship is complex, but that the agreements between the Greek text of Jeremiah and the Hebrew text of Kings support the view that the Old Greek of Jeremiah reflects an early Hebrew version of the book. [ABSTRACT FROM AUTHOR]

Rationale: Selective serotonin reuptake inhibitor (SSRI) antidepressants are increasingly prescribed during pregnancy. Changes in serotonergic signaling during human fetal development have been associated with changes in brain development and with changes in affective behavior in adulthood. The suprachiasmatic nucleus (SCN) is known to be modulated by serotonin and it is therefore assumed that SSRIs may affect circadian rhythms. However, effects of perinatal SSRI treatment on circadian system functioning in the offspring are largely unknown. Objective: Our aim was to investigate the effects of perinatal exposure to the SSRI fluoxetine (FLX) on circadian behavior, affective behavior, and 5-HT1A receptor sensitivity in female rats. In addition, we studied the expression of clock genes and the 5-HT1A receptor in the SCN, as they are potentially involved in underlying mechanisms contributing to changes in circadian rhythms. Results: Perinatal FLX exposure shortened the free-running tau in response to the 5-HT1A/7 agonist 8-OH-DPAT. However, FLX exposure did not alter anxiety, stress coping, and 5-HT1A receptor sensitivity. No differences were found in 5-HT1A receptor and clock genes Per1, Per2, Cry1, and Cry2 SCN gene expression. Conclusions: Perinatal FLX exposure altered the response to a phase-shifting challenge in female rats, whether this may pose health risks remains to be investigated. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to evaluate the clinical accuracy of virtual orthodontic setups by using a new CBCT-based approach. Materials and methods: Ten patients who underwent pre-surgical orthodontics were included in this study. Pre-treatment and pre-surgical cone-beam CT (CBCT) scans and digital dental models were available. The pre-treatment digital dental model was used to create an orthodontic virtual setup. The digital dental models were fused with the corresponding CBCT scans, and the two CBCT scans were aligned using voxel-based matching. Moving each individual tooth from the virtual setup to the final outcome allows the calculation of the accuracy of the virtual setup by using an iterative closest point algorithm. Differences between virtual setup and final outcome were recorded as well as the ICC between two observers. Results: The inter-observer variability showed a high level of agreement between the observers. The largest mean difference between observers was found in the cranial/caudal direction (0.36 ± 0.30 mm) and the roll rotation (1.54 ± 0.98°). Differences between the virtual setup and final outcome were small in the translational direction (0.45 ± 0.48 mm). Rotational mean differences were larger with the pitch of the incisors (0.00 ± 7.97°) and molars (0.01 ± 10.26°) as largest difference. Excessive extrusion of all upper teeth and more anterior movement than planned were seen for both upper and lower arch. Lower molars showed less extrusion. Clinical relevance: The data of this study can be used to obtain more insight in the accuracy and achievability of orthodontic virtual setup. Tooth movement can now be studied in more details which can lead to new insights. [ABSTRACT FROM AUTHOR]

Maurotoxin (MTX) is a 34-residue peptide from Scorpio maurus venom. It is reticulated by four disulfide bridges with a unique arrangement compared to other scorpion toxins that target potassium (K+) channels. Structure–activity relationship studies have not been well performed for this toxin family. The screening of Scorpio maurus venom was performed by different steps of fractionation, followed by the ELISA test, using MTX antibodies, to isolate an MTX-like peptide. In vitro, in vivo and computational studies were performed to study the structure–activity relationship of the new isolated peptide. We isolated a new peptide designated MTX1, structurally related to MTX. It demonstrated toxicity on mice eight times more effectively than MTX. MTX1 blocks the Kv1.2 and Kv1.3 channels, expressed in Xenopus oocytes, with IC50 values of 0.26 and 180 nM, respectively. Moreover, MTX1 competitively interacts with both 125I-apamin (IC50 = 1.7 nM) and 125I-charybdotoxin (IC50 = 5 nM) for binding to rat brain synaptosomes. Despite its high sequence similarity (85%) to MTX, MTX1 exhibits a higher binding affinity towards the Kv1.2 and SKCa channels. Computational analysis highlights the significance of specific residues in the β-sheet region, particularly the R27, in enhancing the binding affinity of MTX1 towards the Kv1.2 and SKCa channels. [ABSTRACT FROM AUTHOR]

Na v 1.1 is an important pharmacological target as this voltage-gated sodium channel is involved in neurological and cardiac syndromes. Channel activators are actively sought to try to compensate for haploinsufficiency in several of these pathologies. Herein we used a natural source of new peptide compounds active on ion channels and screened for drugs capable to inhibit channel inactivation as a way to compensate for decreased channel function. We discovered that JzTx-34 is highly active on Na v 1.1 and subsequently performed a full structure-activity relationship investigation to identify its pharmacophore. These experiments will help interpret the mechanism of action of this and formerly identified peptides as well as the future identification of new peptides. We also reveal structural determinants that make natural ICK peptides active against Na v 1.1 challenging to synthesize. Altogether, the knowledge gained by this study will help facilitate the discovery and development of new compounds active on this critical ion channel target. [ABSTRACT FROM AUTHOR]

• Non-Dutch student cyclists report more accidents than Dutch cyclists. • After three months control of the bicycle by non-Dutch cyclists is similar to the Dutch. • Non-Dutch students make more serious errors in Dutch traffic, Dutch make more mild errors. Thirty-seven young adult participants completed a bicycle ride through the city of Groningen. Behaviour of Dutch and non-Dutch cyclists was compared in three conditions: on a control track (i.e. a one-way bicycle path), on a complex intersection, and on a roundabout. Basic bicycle control of the two groups did not differ, neither did reported invested mental effort. However, non-Dutch participants made more serious errors in the experiment and reported to have had more crashes previous to the experiment. It is concluded that the performance of non-Dutch cyclists who continue cycling upon arrival in a new country, does not differ on the control level, but at the higher manoeuvre level more performance errors were observed in the non-Dutch group. [ABSTRACT FROM AUTHOR]

Provides information on a study which examined the heat transfer inside cylindrical resistance diffusion and low-pressure chemical vapor deposition furnaces aimed at developing an improved temperature controller. Model of thermal behavior; Thermal behavior of the thermocouples; Model of an alternative temperature controller of the linear quadratic Gaussian type model.

Provides information on a study which detailed thermomigration experiments on vapor-deposited films of pure indium and of indium with addition of silver, gallium, lead, and antimony. Situation that promotes internal laser degradation; Cause of the increase in thermal resistance between the laser chip and the heat sink; Reason for the arousal of the temperature gradient.

Trichoptera, or caddisflies, are common members of freshwater ecosystems as larvae and are important indicators of aquatic system health. As such, the species are relatively well studied, with keys available for larvae and adults of many of the taxa occurring in Canada. The number of species recorded from Canada since 1979 (Wiggins 1979) has increased from 546 to 636, an increase of 16.4%. Of those species newly recorded, 17 represent newly described taxa since 1979. Taking into consideration the species likely to be subsequently found in Canada based on records in adjacent parts of the United States and results from DNA barcoding, an estimated 129-181 species remain to be documented in Canada. [ABSTRACT FROM AUTHOR]

The currently documented fauna of described species of myriapods in Canada includes 54 Chilopoda, 66 Diplopoda, 23 Pauropoda, and two Symphyla, representing increases of 24, 23, 23, and one species, respectively, since 1979. Of the 145 myriapod species currently documented, 40 species are not native to Canada. The myriapods have not been well documented with DNA barcodes and no barcodes are available for Pauropoda. It is conservatively estimated that at least 93 additional myriapods species will be discovered in Canada: Chilopoda (40), Diplopoda (29), Pauropoda (17), and Symphyla (seven). In general, there is a serious dearth of knowledge about myriapods in Canada, and systematics research and surveys continue to be needed to help document the diversity and distribution of these groups in the country. [ABSTRACT FROM AUTHOR]

Summary: In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites.Introduction: To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally—in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters.Methods: Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history.Results: After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (− 4%) in prediabetes and smaller cross-sectional area of the tibia (− 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (− 5%), cortical thickness (− 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (− 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters.Conclusions: In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract This study focussed on investigating the coupling of continuous manufacturing of drug substance and continuous manufacture of drug product. An important step in such an integrated end-to-end continuous manufacturing was envisioned by dosing the API as suspension into a twin-screw wet granulation process. To achieve this goal, a model drug substance (ibuprofen) was fed as a concentrated aqueous suspension (50% w/w) into a twin-screw granulator and compared against traditional solid feeding of the model drug substance to meet a target ibuprofen load of 60% w/w in the formulation. Granulation and compaction behaviour were evaluated to determine the impact of feeding API as suspension in twin-screw wet granulation on the critical quality attributes of the drug product. It was demonstrated that the ibuprofen suspension feed is comparable with the ibuprofen dry blend feed in twin-screw wet granulation. Next to enabling end-to-end continuous manufacturing, API suspension feed in twin-screw wet granulation could afford a number of additional advantages including manufacturing efficiency by removing the drying step for API, or overcoming processing issues linked to the bulk properties of the API powder (e.g. flowability). [ABSTRACT FROM AUTHOR]

Most HR-pQCT studies examining cortical bone use an automatically generated endocortical contour (AUTO), which is manually corrected if it visually deviates from the apparent endocortical margin (semi-automatic method, S-AUTO). This technique may be prone to operator-related variability and is time consuming. We examined whether the AUTO instead of the S-AUTO method can be used for cortical bone analysis. Fifty scans of the distal radius and tibia from participants of The Maastricht Study were evaluated with AUTO, and subsequently with S-AUTO by three independent operators. AUTO cortical bone parameters were compared to the average parameters obtained by the three operators (S-AUTOmean). All differences in mean cortical bone parameters between AUTO and S-AUTOmean were < 5%, except for lower AUTO cortical porosity of the radius (- 16%) and tibia (- 6%), and cortical pore volume (Ct.Po.V) of the radius (- 7%). The ICC of S-AUTOmean and AUTO was > 0.90 for all parameters, except for cortical pore diameter of the radius (0.79) and tibia (0.74) and Ct.Po.V of the tibia (0.89), without systematic errors on the Bland-Altman plots. The precision errors (RMS-CV%) of the radius parameters between S-AUTOmean and AUTO were comparable to those between the individual operators, whereas the tibia RMS-CV% between S-AUTOmean and AUTO were higher than those of the individual operators. Comparison of the three operators revealed clear inter-operator variability. This study suggests that the AUTO method can be used for cortical bone analysis in a cross-sectional study, but that the absolute values-particularly of the porosity-related parameters-will be lower. [ABSTRACT FROM AUTHOR]

Chromatographic retention time peak shifts between consecutive analyses is a well-known fact yet not fully understood. Algorithms have been developed to align peaks between runs, but with no specific studies considering the causes of peak shifts. Here, designed experiments reveal chromatographic shift patterns for a complex peptide mixture that are attributable to the temperature and pH of the mobile phase. These results demonstrate that peak shifts are highly structured and are to a high degree explained by underlying differences in physico-chemical parameters of the chromatographic system and also provide experimental support for the alignment algorithm called the generalized fuzzy Hough transform which exploits this fact. It can be expected that the development of alignment algorithms enters a new phase resulting in increasingly accurate alignment by considering the latent structure of the peak shifts. [ABSTRACT FROM AUTHOR]

Introduction: Community-dwelling older persons often experience hindering health complaints that disturb daily activities. If general practitioners (GPs) are unaware of such complaints, this could lead to a mismatch in provided care and needed or expected care. In this qualitative study with community-dwelling older persons we investigated how older persons experience hindering health complaints, how they deal with them, and what they expect from their GP. Methods: Participants (aged ≥80 years) with pain and/or problems with walking/standing were invited to participate in a (group)interview about hindering health problems and expectations from general practice. Data were analysed using the framework method and results were discussed with a client panel. Results: Participants experienced various hindering health complaints in addition to pain and/or problems with walking/standing. Complaints affecting social activities were experienced as the most hindering. Participants actively tried to remain independent and, to achieve this, GPs were expected to be involved and be easily accessible. However, they did not expect specific help from their GP for pain or problems with walking/standing. Suggestions for improvement of care from GPs included optimisation of accessibility (continuous availability by telephone), a yearly check including medication review, open communication, and empathy and support during major life events. Conclusions: According to older persons with hindering health complaints, GPs could improve their accessibility/relationship with patients by: 1) continuous telephonic availability, 2) initiating regular contact with medication reviews, and 3) initiating support during major life events. This might lower the reported barriers to contact the GP for hindering health complaints. [ABSTRACT FROM AUTHOR]

Objective: Understanding patient satisfaction from the perspective of older adults is important to improve quality of their care. Since patient and care variables which can be influenced are of specific interest, this study examines the relation between patient satisfaction and the perceived doctor-patient relationship in older persons and their general practitioners (GPs). Design: Cross-sectional survey. Subjects and setting: Older persons (n=653, median age 87 years; 69.4% female) living in 41 residential homes. Main outcome measures: Patient satisfaction (report mark) and perceived doctor-patient relationship (Leiden Perioperative care Patient Satisfaction questionnaire); relationships were examined by comparing medians and use of regression models. Results: The median satisfaction score was 8 (interquartile range 7.5-9; range 0-10) and doctorpatient relationship 65 (interquartile range 63-65; range 13-65). Higher satisfaction scores were related to higher scores on doctor-patient relationship (Jonckheere Terpstra test, p for trend <.001) independent of gender, age, duration of stay in the residential home, functional and clinical characteristics. Adjusted for these characteristics, per additional point for doctor-patient relationship, satisfaction increased with 0.103 points (β=0.103, 95% CI 0.092-0.114; p<.001). In those with a 'low' doctor-patient relationship rating, the percentage awarding 'sufficient or good' to their GP for 'understanding about the personal situation' was 12%, 'receiving attention as an individual' 22%, treating the patient kindly 78%, and being polite 94%. Conclusion: In older persons, perceived doctor-patient relationship and patient satisfaction are related, irrespective of patient characteristics. GPs may improve patient satisfaction by focusing more on the affective aspects of the doctor-patient relationship. [ABSTRACT FROM AUTHOR]

Objectives: Providing parenteral amino acids to very-low-birth-weight infants during the first weeks of life is critical for adequate growth and neurodevelopment. However, there is no consensus about what dose is appropriate or when to initiate supplementation. As a result, daily practice varies among neonatal intensive care units. The objective of our study was to determine the effects of early parenteral amino-acid supplementation (within 24 h of birth) versus later initiation and high dose (>3.0 g/kg/day) versus a lower dose on growth and morbidities. Methods: A systematic review and meta-analysis of publications identified by searching PubMed, EMBASE, and Cochrane databases was conducted. Randomized controlled studies were eligible if information on growth was available. Results: The search identified 14 studies. No differences were observed in growth or morbidity after early or high-dose amino-acid supplementation, but for several outcomes, meta-analysis was not possible due to study heterogeneity. Initiation of amino acids within the first 24 h of life appeared to be safe and well tolerated, and leads more rapidly to a positive nitrogen balance. Conclusions: Administering a high dose (>3.0 g/kg/day) or an early dose (≤24 h) of parenteral amino acids is safe and well tolerated but does not offer significant benefits on growth. Further large-scale randomized controlled trials in preterm infants are needed to study the effects of early and high-dose amino acids on growth and morbidity more consistently and extensively. [ABSTRACT FROM AUTHOR]

• first- and third-person perspective was compared in a driving simulator. • third-person perspective affects driving behaviour and reduces presence. • No difference in simulator sickness between perspectives. • A third-person perspective is not advised for driving simulator behavioural research. This study explores the effects of changing the viewing perspective from a first-person perspective (a traditional viewing perspective in virtual reality) to a third-person perspective (a view from behind the vehicle, as used in many computer games) on driving behaviour, presence, and simulator sickness. In a driving simulator participants drove the same route twice, once for each perspective. Measures for driving behaviour were recorded during the rides, and both simulator sickness and feeling of presence were measured after each ride. Participants also evaluated the perspectives for the different situations they encountered. Results show that changing viewing perspectives leads to a lower feeling of presence, but does not result in lower simulator sickness scores. While lane control is similar between perspectives, participants drove faster and more to the left in the third-person perspective. The first-person perspective was evaluated more positively in all situations, and was preferred by almost all participants. These results indicate that a third-person perspective is unlikely to be an effective method for reducing simulator sickness in driving simulators, and the results show that the third-person perspective is not advised in driving simulator behavioural research. [ABSTRACT FROM AUTHOR]

Background Stroke/death rates within 30 days of carotid endarterectomy (CEA) and carotid artery stenting (CAS) in RCTs inform current clinical guidelines. However, the risks may have changed in recent years with wider use of effective stroke prevention therapies, especially statins, improved patient selection and growing operator expertise. The aim of this study was to investigate whether the procedural stroke/death risks from CEA and CAS have changed over time. Methods MEDLINE and Embase were searched systematically from inception to May 2016 for observational cohort studies of CEA and CAS. Studies included reported on more than 1000 patients, with 30-day outcomes after the procedure according to patients' symptom status (recent stroke or transient ischaemic attack). Restricted maximum likelihood random-effects and meta-regressions methods were used to synthesize procedural stroke/death rates of CEA and CAS according to year of study recruitment completion. Results Fifty-one studies, including 223 313 patients undergoing CEA and 72 961 undergoing CAS, were reviewed. Procedural stroke/death risks of CEA decreased over time in symptomatic and asymptomatic patients. Risks were substantially lower in studies completing recruitment in 2005 or later, both in symptomatic (5·11 per cent before 2005 versus 2·68 per cent from 2005 onwards; P = 0·002) and asymptomatic (3·17 versus 1·50 per cent; P < 0·001) patients. Procedural stroke/death rates of CAS did not change significantly over time (4·77 per cent among symptomatic and 2·59 per cent among asymptomatic patients). There was substantial heterogeneity in event rates and recruitment periods were long. Conclusions Risks of procedural stroke/death following CEA appear to have decreased substantially. There was no evidence of a change in stroke/death rates following CAS. [ABSTRACT FROM AUTHOR]

Background: EarlyNutrition ( www.project-earlynutrition.eu ) is an international research consortium investigating the effects of early nutrition on metabolic programming.Objective: To summarize current evidence and standards, recommendations, guidelines, and regulations on nutrition or supplements in lactating women with emphasis placed on long-term health effects in offspring, including cardiovascular disease, hypertension, overweight/obesity, metabolic syndrome, diabetes, or glucose intolerance.Methods: Medline, Embase, selected databases and websites were searched for documents published between 2010 and 2015.Results: Thirteen documents met the inclusion criteria. Effects of maternal long-chain polyunsaturated fatty acid (LC-PUFA) supplementation on overweight/obesity or hypertension in offspring were assessed in 10 studies. One study described the effect of maternal vitamin D supplementation on overweight/obesity, and the remaining 2 studies assessed the effects of maternal probiotic/synbiotic supplementation during lactation on overweight/obesity or metabolic syndrome in their infants. Forty-one documents contained dietary recommendations on various macro- and micronutrients for lactating women, but without consideration of our long-term health outcomes in infants.Conclusion: Literature on nutrition of lactating women and its effect on their infants' later health with respect to metabolic programming outcomes appeared to be scarce, and focused mostly on supplementation of LC-PUFA's. No recent guidelines or recommendations were available, highlighting the significant research gaps regarding this topic. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of fractures, despite normal to increased bone mineral density (BMD). Insulin use is one of the factors linked to this increased fracture risk. However, direct negative effects of insulin on bone quality are not expected since insulin is thought to be anabolic to bone. In this cross-sectional study the association between insulin use and volumetric BMD (vBMD), bone micro-architecture and bone strength of the distal radius, as measured with HR-pQCT, was examined. Data from 50 participants with T2DM of The Maastricht Study (mean age 62 ± 7.5 years, 44% women) was used. Participants were classified as insulin user (n = 13) or non-insulin user (n = 37) based on prescription data. Linear regression analysis was used to estimate the association between current insulin use and HR-pQCT derived parameters. After adjustment for age, sex, body mass index, glycated hemoglobin A1c and T2DM duration, insulin use was associated with lower total vBMD (standardized beta (β):− 0.56 (95% CI:− 0.89 to − 0.24)), trabecular vBMD (β:− 0.58 (95% CI:− 0.87 to − 0.30)), trabecular thickness (β:− 0.55 (95% CI:− 0.87 to − 0.23)), cortical thickness (β:− 0.41 (95% CI:− 0.74 to − 0.08)), log cortical pore volume (β:− 0.43 (95% CI:− 0.73 to − 0.13)), bone stiffness (β:− 0.39 (95% CI:− 0.62 to − 0.17)) and failure load (β:− 0.39 (95% CI:− 0.60 to − 0.17)) when compared to the non-insulin users. Insulin use was not associated with cortical vBMD, trabecular number, trabecular separation, cortical porosity and cortical pore diameter. This study indicates that insulin use is negatively associated with bone density, bone micro-architectural and bone strength parameters. These findings may partly explain the previously observed increased fracture risk in insulin users, although there may be residual confounding by other factors related to disease severity in insulin users. [ABSTRACT FROM AUTHOR]

As a cyclist, it is essential to make inferences about the intentions of other road users in order to anticipate their behaviour. There are official ways for cyclists to communicate their intentions to other road users, such as using their arms to point in the intended direction of travel. However, in everyday traffic cyclists often do not use such active forms of communication. Therefore, other visual cues have to be used to anticipate (critical) encounters or events. During this study, 108 participants completed a video internet survey in which they predicted the intentions of a lead cyclist based on visible behaviour preceding a turning manoeuvre. When the lead cyclist approached the intersection, each video was stopped just before the cyclist initiated turning. Based on visual cues, the participants had to select which direction they thought the cyclist would go. After entering their prediction, they were asked how certain they were about their prediction and on which visible behaviour(s) each prediction was based. The results show that it is very hard to predict the direction of a turning cyclist based on visual cues before the turning manoeuvre is initiated. Exploratory regression analyses revealed that observable behaviours such as head movements and cycling speed were related to prediction accuracy. These results may be used to support cyclists in traffic interactions. [ABSTRACT FROM AUTHOR]

Background: Very preterm infants often receive donor milk from mothers who deliver at term, but its composition differs from that of their own mother's milk. Because breast-milk glucocorticoids can support developing neonates, we explored concentration variability within and between mothers.Objective: We hypothesized that breast-milk glucocorticoid concentrations would be higher after very preterm delivery [gestational age (GA) <32 wk; study 1] and would follow the diurnal rhythm of maternal adrenocortical activity (study 2).Methods: Study 1 assessed differences in milk cortisol, cortisone, and the cortisone-to-(cortisol+cortisone) ratio of mothers who delivered at (median) GA: 28.6 wk or at term weekly during the first month postpartum. Study 2 assessed variations in milk cortisol, cortisone, and the cortisone-to-(cortisol+cortisone) ratio over 24 h, and tested Pearson correlations between milk and salivary concentrations in mothers who delivered at term (median GA: 38.9 wk) during week 4 postpartum. In these studies, foremilk glucocorticoids were measured by liquid chromatography-tandem mass spectrometry. Associations of milk cortisol, milk cortisone, and the milk cortisone-to-(cortisol+cortisone) ratio with prematurity (study 1) or collection time (study 2) were studied with longitudinal data analyses.Results: In study 1, giving birth to a very preterm infant was associated with reductions in milk cortisol and cortisone concentrations of 50% (β: 0.50; 95% CI: 0.26, 0.99; P = 0.05) and 53% (β: 0.53; 95% CI: 0.30, 0.93; P = 0.03), respectively, when adjusted for collection time. In study 2, concentrations of milk cortisol and cortisone were associated with collection time (both P < 0.01), peaking at ∼0700. Milk and salivary concentrations of cortisol (r = 0.92, P < 0.01) and cortisone (r = 0.93, P < 0.01) as well as the cortisone-to-(cortisol+cortisone) ratio (r = 0.64, P < 0.01) were correlated with one another.Conclusions: Breast-milk glucocorticoid concentrations follow the diurnal rhythm of maternal hypothalamus-pituitary-adrenal axis activity and are lower in mothers who deliver very preterm. [ABSTRACT FROM AUTHOR]