Nanophotonics of higher-plant photosynthetic membranes.

The thylakoid membrane inside chloroplasts hosts the light-dependent reactions of photosynthesis. Its embedded protein complexes are responsible for light harvesting, excitation energy transfer, charge separation, and transport. In higher plants, when the illumination conditions vary, the membrane adapts its composition and nanoscale morphology, which is characterized by appressed and non-appressed regions known as grana and stroma lamellae, respectively. Here we investigate the nanophotonic regime of light propagation in chloroplasts of higher plants and identify novel mechanisms in the optical response of the thylakoid membrane. Our results indicate that the relative contributions of light scattering and absorption to the overall optical response of grana strongly depend on the concentration of the light-harvesting complexes. For the pigment concentrations typically found in chloroplasts, the two mechanisms have comparable strengths, and their relative value can be tuned by variations in the protein composition or in the granal diameter. Furthermore, we find that collective modes in ensembles of grana significantly increase light absorption at selected wavelengths, even in the presence of moderate biological disorder. Small variations in the granal separation or a large disorder can dismantle this collective response. We propose that chloroplasts use this mechanism as a strategy against dangerously high illumination conditions, triggering a transition to low-absorbing states. We conclude that the morphological separation of the thylakoid membrane in higher plants supports strong nanophotonic effects, which may be used by chloroplasts to regulate light absorption. This adaptive self-organization capability is of interest as a model for novel bioinspired optical materials for artificial photosynthesis, imaging, and sensing.

The interpretation of change score of the pain disability index after vocational rehabilitation is baseline dependent.

BACKGROUND: The Pain Disability Index (PDI) is a widely-used instrument to measure pain-related disability. The aim of this study was to assess the responsiveness and interpretation of change score of the PDI in patients with chronic musculoskeletal pain (CMP) at discharge of vocational rehabilitation. METHODS: Retrospective data of patients with CMP who attended vocational rehabilitation between 2014 and 2017 was used. The anchor-based method was used to assess the responsiveness of the total sample and of PDI baseline quartile groups. A receiver operating characteristic curve was performed, including Area Under the Curve (AUC) and Minimal Important Change (MIC). RESULTS: The PDI showed responsive to detect clinically relevant changes in pain-related disability at discharge of vocational rehabilitation (AUC 0.79). A PDI change score of 13 points (MIC 12.5) can be considered as a real change in pain-related disability for the total study sample, and a PDI change score of 7-20 points can be considered as a real change in pain-related disability for PDI lowest and highest baseline quartile scores. CONCLUSION: The PDI is responsive in patients with CMP at discharge of vocational rehabilitation. The interpretation of change score depends on PDI baseline score. Patients with a PDI baseline score of ≤27 should decrease minimal 7 points, patients with a baseline score between 28 and 42 should decrease minimal 15 points, and patients with a baseline score ≥ 43 should decrease minimal 20 points.

Upregulation of CD38 expression on multiple myeloma cells by all-trans retinoic acid improves the efficacy of daratumumab.

Daratumumab is an anti-CD38 monoclonal antibody with lytic activity against multiple myeloma (MM) cells, including ADCC (antibody-dependent cellular cytotoxicity) and CDC (complement-dependent cytotoxicity). Owing to a marked heterogeneity of response to daratumumab therapy in MM, we investigated determinants of the sensitivity of MM cells toward daratumumab-mediated ADCC and CDC. In bone marrow samples from 144 MM patients, we observed no difference in daratumumab-mediated lysis between newly diagnosed or relapsed/refractory patients. However, we discovered, next to an expected effect of effector (natural killer cells/monocytes) to target (MM cells) ratio on ADCC, a significant association between CD38 expression and daratumumab-mediated ADCC (127 patients), as well as CDC (56 patients). Similarly, experiments with isogenic MM cell lines expressing different levels of CD38 revealed that the level of CD38 expression is an important determinant of daratumumab-mediated ADCC and CDC. Importantly, all-trans retinoic acid (ATRA) increased CD38 expression levels but also reduced expression of the complement-inhibitory proteins CD55 and CD59 in both cell lines and primary MM samples. This resulted in a significant enhancement of the activity of daratumumab in vitro and in a humanized MM mouse model as well. Our results provide the preclinical rationale for further evaluation of daratumumab combined with ATRA in MM patients.

Different value of coronary calcium score to predict obstructive coronary artery disease in patients with and without moderate chronic kidney disease.

PURPOSE: The coronary calcium score (CCS) predicts significant coronary artery disease (CAD) in the general population. While moderate chronic kidney disease (CKD) is associated with high CCS, the use of CCS to predict significant CAD in these patients is unknown. METHODS: A total of 704 patients underwent computed tomography coronary angiography for the assessment of CCS and CAD. Sixty-nine (10 %) patients had moderate CKD, defined by an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/min/1.73m(2), and the remaining patients were considered to be without significant CKD (eGFR ≥ 60 mL/min/1.73m(2)). RESULTS: Patients with moderate CKD were older, had a higher CCS, and a higher prevalence of obstructive CAD than patients without significant CKD. Receiver-operator curve analysis showed that CCS predicted the presence of obstructive CAD in both patients with moderate CKD and those without significant CKD. In patients with moderate CKD, the optimal cut-off value of CCS to diagnose obstructive CAD was 140 (sensitivity 73 % and specificity of 70 %), and is 2.8 fold higher than in patients without significant CKD (cut-off value = 50; sensitivity 75 % and specificity 75 %). CONCLUSION: The present results demonstrate that CCS can predict obstructive CAD in patients with moderate CKD, although the optimal cut-off value is higher than in patients without significant CKD.

Towards an ICF- and IMMPACT-based pain vocational rehabilitation core set in the Netherlands.

BACKGROUND: For clinical use and research of pain within the context of vocational rehabilitation, a specific core set of measurements is needed. The recommendations of the International Classification of Functioning, Disability and Health (ICF) brief Core Set for Vocational Rehabilitation (VR) and those of Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) cover two broad areas. These two sources can be integrated when made applicable to vocational rehabilitation and pain. Objective To develop a core set of diagnostic and evaluative measures specifically for vocational rehabilitation of patients with subacute and chronic musculoskeletal pain, while using the brief ICF core set for VR as the reference framework in VR, and the IMMPACT recommendations in the outcome measurements around pain. METHODS: Three main steps were taken. The first step was to remove irrelevant and duplicate domains of the brief ICF Core Set for Vocational Rehabilitation and the IMMPACT recommendations around pain. The second step was to match the remaining domains with existing instruments or measures. Instruments were proposed based on availability and its proven use in Dutch practice and based on proof of sufficient clinimetric properties. In step 3, the preliminary VR-Pain core set was presented to 3 expert panels: proposed users, Dutch pain rehabilitation experts, and international VR experts. RESULTS: Experts agreed with the majority of the proposed domains and instruments. The final VR-Pain Core Set consists of 18 domains measured with 12 instruments. All instruments possessed basic clinimetric properties. CONCLUSION: An agreed-upon VR-Pain Core Set with content that covers relevant domains for pain and VR and validated instruments measuring these domains has been developed. The VR-Pain Core Set may be used for regular clinical purposes and research in the field of vocational rehabilitation and pain, but adaptations should be considered for use outside the Netherlands.

Non-invasive assessment of atherosclerotic coronary lesion length using multidetector computed tomography angiography: comparison to quantitative coronary angiography.

Multidetector computed tomography angiography (CTA) provides information on plaque extent and stenosis in the coronary wall. More accurate lesion assessment may be feasible with CTA as compared to invasive coronary angiography (ICA). Accordingly, lesion length assessment was compared between ICA and CTA in patients referred for CTA who underwent subsequent percutaneous coronary intervention (PCI). 89 patients clinically referred for CTA were subsequently referred for ICA and PCI. On CTA, lesion length was measured from the proximal to the distal shoulder of the plaque. Quantitative coronary angiography (QCA) was performed to analyze lesion length. Stent length was recorded for each lesion. In total, 119 lesions were retrospectively identified. Mean lesion length on CTA was 21.4 ± 8.4 mm and on QCA 12.6 ± 6.1 mm. Mean stent length deployed was 17.4 ± 5.3 mm. Lesion length on CTA was significantly longer than on QCA (difference 8.8 ± 6.7 mm, P < 0.001). Moreover, lesion length visualized on CTA was also significantly longer than mean stent length (CTA lesion length-stent length was 4.2 ± 8.7 mm, P < 0.001). Lesion length assessed by CTA is longer than that assessed by ICA. Possibly, CTA provides more accurate lesion length assessment than ICA and may facilitate improved guidance of percutaneous treatment of coronary lesions.

Performance and efficacy of 320-row computed tomography coronary angiography in patients presenting with acute chest pain: results from a clinical registry.

The purpose of this study was to evaluate the performance of 320-row computed tomography angiography (CTA) in the identification of significant coronary artery disease (CAD) in patients presenting with acute chest pain and to examine the relation to outcome during follow-up. A total of 106 patients with acute chest pain underwent CTA to evaluate presence of CAD. Each CTA was classified as: normal, non-significant CAD (<50% luminal narrowing) and significant CAD (≥50% luminal narrowing). CTA results were compared with quantitative coronary angiography. After discharge, the following cardiovascular events were recorded: cardiac death, non-fatal infarction, and unstable angina requiring revascularization. Among the 106 patients, 23 patients (22%) had a normal CTA, 19 patients (18%) had non-significant CAD on CTA, 59 patients (55%) had significant CAD on CTA, and 5 patients (5%) had non-diagnostic image quality. In total, 16 patients (15%) were immediately discharged after normal CTA and 90 patients (85%) underwent invasive coronary angiography. Sensitivity, specificity, and positive and negative predictive values to detect significant CAD on CTA were 100, 87, 93, and 100%, respectively. During mean follow-up of 13.7 months, no cardiovascular events occurred in patients with a normal CTA examination. In patients with non-significant CAD on CTA, no cardiac death or myocardial infarctions occurred and only 1 patient underwent revascularization due to unstable angina. In patients presenting with acute chest pain, an excellent clinical performance for the non-invasive assessment of significant CAD was demonstrated using CTA. Importantly, normal or non-significant CAD on CTA predicted a low rate of adverse cardiovascular events and favorable outcome during follow-up.

Functional capillary density decreases after the first week of life in term neonates.

BACKGROUND: Changes in the microcirculation have been recognized to play a crucial role in many disease processes. In premature neonates, functional capillary density (FCD) decreases during the first months of life. OBJECTIVES: The aims of this study were to obtain microcirculatory parameters in term neonates and older children who did not present with compromised respiration or circulation and to determine developmental changes in the microcirculation in young children. METHODS: This single-center prospective observational study was performed at a level III university children's hospital. Subjects eligible for inclusion were children up to the age of 3 years who did not have any respiratory compromise, circulatory compromise or signs of dehydration. The buccal mucosa of 45 children was assessed, using orthogonal polarization spectral imaging. RESULTS: We found a significantly higher FCD in neonates younger than 1 week compared with older children. The median FCD was 8.1 cm/cm(2) (range 7.3-9.4) for 0- to 7-day-old neonates (n = 12), 6.9 cm/cm(2) (range 4.7-8.7) for 8- to 28-day-olds (n = 10), 7.3 cm/cm(2) (range 6.1-8.8) for 1- to 6-month-olds (n = 19) and 6.7 cm/cm(2) (range 6.5-9.2) for 3-year-olds (n = 4). After the first week, there was no significant correlation between age and FCD. CONCLUSION: FCD of the buccal mucosa decreases after the first week of life.

Clinical application of CT coronary angiography: state of the art.

In recent years, multi-slice computed tomography (MSCT) technology has developed rapidly, allowing high-resolution non-invasive imaging of the coronary arteries and surrounding structures. Since the introduction of MSCT, acquisition time, detector number, spatial and temporal resolution have continuously improved with each new scanner generation, resulting in excellent image quality and diagnostic accuracy in the detection of coronary artery disease (CAD). At the same time, developments in MSCT technology have focused on reduction of the radiation dose. In particular, the availability of dose modulation and prospective ECG gating have drastically reduced patient radiation dose. Moreover, with the introduction of 320-slice MSCT, volumetric scanning of the entire heart has become possible in a single heart beat or gantry rotation, thereby eliminating oversampling and stair-step artifact. The present article provides an overview of state of the art clinical applications of cardiac MSCT, including the diagnosis of CAD, evaluation of plaque morphology and composition, prognostification, and the evaluation of left ventricular function and aortic and mitral valve anatomy.

Plaque type and composition as evaluated non-invasively by MSCT angiography and invasively by VH IVUS in relation to the degree of stenosis.

BACKGROUND: Imaging of coronary plaques has traditionally focused on evaluating degree of stenosis, as the risk for adverse cardiac events increases with stenosis severity. However, the relation between plaque composition and severity of stenosis remains largely unknown. OBJECTIVE: To assess plaque composition (non-invasively by multislice computed tomography (MSCT) angiography and invasively by virtual histology intravascular ultrasound (VH IVUS)) in relation to degree of stenosis. METHODS: 78 patients underwent MSCT (identifying three plaque types; non-calcified, calcified, mixed) followed by invasive coronary angiography and VH IVUS. VH IVUS evaluated plaque burden, minimal lumen area and plaque composition (fibrotic, fibro-fatty, necrotic core, dense calcium) and plaques were classified as fibrocalcific, fibroatheroma, thin-capped fibroatheroma (TCFA), pathological intimal thickening. For each plaque, percentage stenosis was evaluated by quantitative coronary angiography. Significant stenosis was defined >50% stenosis. RESULTS: Overall, 43 plaques (19%) corresponded to significant stenosis. Of the 227 plaques analysed, 70 were non-calcified plaques (31%), 96 mixed (42%) and 61 calcified (27%) on MSCT. Plaque types on MSCT were equally distributed among significant and non-significant stenoses. VH IVUS identified that plaques with significant stenosis had higher plaque burden (67% (11%) vs 53% (12%), p<0.05) and smaller minimal lumen area (4.6 (3.8-6.8) mm(2) vs 7.3 (5.4-10.5) mm(2), p<0.05). Interestingly, no differences were observed in percentage fibrotic, fibro-fatty, necrotic core and dense calcium. Non-significant stenoses were more frequently classified as pathological intimal thickening (46 (25%) vs 3 (7%), p<0.05), although TCFA (more vulnerable plaque) was distributed equally (p = 0.18). CONCLUSION: No evident association exists between the degree of stenosis and plaque composition or vulnerability, as evaluated non-invasively by MSCT and invasively by VH IVUS.

How many people return to work after acquired brain injury?: a systematic review.

PRIMARY OBJECTIVE: To investigate how many people return to work (RTW) after acquiring brain injury (ABI) due to traumatic or non-traumatic causes. Secondary objectives were to investigate the differences in outcome between traumatic and non-traumatic causes, the development of RTW over time and whether or not people return to their former job. METHODS: A systematic literature search (1992-2008) was performed using terms of ABI and RTW. The methodological quality of the studies was determined. An overall estimation of percentage RTW 1 and 2 years post-injury was calculated by data pooling. MAIN OUTCOMES AND RESULTS: Finally, 49 studies were included. Within 2 years post-injury, 39.3% of the subjects with non-traumatic ABI returned to work. Among people with traumatic ABI, 40.7% returned to work after 1 year and 40.8% after 2 years. No effect of cause or time since injury was found. Some people with traumatic ABI who returned to work were not able to sustain their job over time. Changes of occupation and job demands are common among people with ABI. CONCLUSIONS: About 40% of the people with traumatic or non-traumatic ABI are able to return to work after 1 or 2 years. Among those with acquired traumatic brain injury a substantial proportion of the subjects were either not able to return to their former work or unable to return permanently.

Prognostic factors of return to work after acquired brain injury: a systematic review.

PRIMARY OBJECTIVE: To provide insight into the prognostic and non-prognostic factors of return to work (RTW) in people with traumatic and non-traumatic acquired brain injury (ABI) who were working before injury. METHODS: A systematic literature search (1992-2008) was performed, including terms for ABI, RTW and prognostic factors. The methodological quality of the studies was determined. Evidence was classified as strong (positive, negative or no), weak or inconsistent. MAIN OUTCOMES AND RESULTS: Following classification of the studies, 22 studies were included. Strong evidence was found that 'gender' and 'anatomic location' were not associated with RTW after non-traumatic ABI and that both 'injury severity' (classified by the Glascow Coma Scale) and 'suffering from depression' or 'anxiety' were not associated with RTW after traumatic ABI. In addition strong evidence was found for the negative prognostic value on RTW of the 'inpatient length of stay', after traumatic ABI. Weak evidence was found for the three trainable/treatable factors 'ability to perform activities of daily living', 'residual physical deficits/higher disability level' and 'number of associated injuries'. CONCLUSION: Strong evidence was found that six variables either had no association or a negative association with RTW. It is recommended to focus in rehabilitation on the factors for which weak evidence was found but that are trainable/treatable with the goal of improving the process of vocational rehabilitation.

Physical capacity and walking ability after lower limb amputation: a systematic review.

OBJECTIVE: To review the influence of physical capacity on regaining walking ability and the development of walking ability after lower limb amputation. DESIGN: A systematic search of literature was performed. The quality of all relevant studies was evaluated according to a checklist for statistical review of general papers. SUBJECTS: Lower limb amputees. MAIN MEASURES: Physical capacity (expressed by aerobic capacity, anaerobic capacity, muscle force, flexibility and balance) and walking ability (expressed by the walking velocity and symmetry). RESULTS: A total of 48 studies that complied with the inclusion criteria were selected. From these studies there is strong evidence for deterioration of two aspects of physical capacity (muscle strength and balance) and of two aspects of walking ability (walking velocity and symmetry) after lower limb amputation. Strong evidence was found for a relation between balance and walking ability. CONCLUSION: Strong evidence was only found for a relation between balance and walking ability. Evidence about a relation between other elements of physical capacity and walking ability was insufficient. Training of physical capacity as well as walking ability during rehabilitation following lower limb amputation should not be discouraged since several parameters have been shown to be reduced after amputation, although their relation to regaining walking ability and to the development of walking ability remains unclear.

Influence of gaze direction on crossmodal modulation of visual ERPS by endogenous tactile spatial attention.

Recent evidence indicates that the spatial direction of endogenous covert spatial attention in one sensory modality can crossmodally influence early processing of stimuli in a different modality. However, spatial locations are initially coded according to different frames of reference for different modalities (e.g., body-centered for touch versus retinocentric vision) and postural changes (e.g., gaze shifts) will realign these. Here, we used event-related potentials (ERPs) to investigate how the direction of endogenous tactile attention affects sensory-specific visual ERP components. Critically, by manipulating direction of gaze, we were able to test whether any crossmodal effects depend on visual and tactile projections to a common hemisphere, on common locations in external space, or on some combination of the two. We found that both P1 and N1 visual components were modulated according to the direction of endogenous tactile attention. While the P1 crossmodal effect followed purely hemispheric constraints, the attentional modulation of N1 appeared to combine both anatomical and external spatial constraints.