Molecularly imprinted nanogels as synthetic recognition materials for the ultrasensitive detection of periodontal disease biomarkers.

Periodontal disease affects supporting dental structures and ranks among one of the top most expensive conditions to treat in the world. Moreover, in recent years, the disease has also been linked to cardiovascular and Alzheimer's diseases. At present, there is a serious lack of accurate diagnostic tools to identify people at severe risk of periodontal disease progression. Porphyromonas gingivalis is often considered one of the most contributing factors towards disease progression. It produces the Arg- and Lys-specific proteases Rgp and Kgp, respectively. Within this work, a short epitope sequence of these proteases is immobilised onto a magnetic nanoparticle platform. These are then used as a template to produce high-affinity, selective molecularly imprinted nanogels, using the common monomers N-tert-butylacrylamide (TBAM), N-isopropyl acrylamide (NIPAM), and N-(3-aminopropyl) methacrylamide hydrochloride (APMA). N,N-Methylene bis(acrylamide) (BIS) was used as a crosslinking monomer to form the interconnected polymeric network. The produced nanogels were immobilised onto a planar gold surface and characterised using the optical technique of surface plasmon resonance. They showed high selectivity and affinity towards their template, with affinity constants of 79.4 and 89.7 nM for the Rgp and Kgp epitope nanogels, respectively. From their calibration curves, the theoretical limit of detection was determined to be 1.27 nM for the Rgp nanogels and 2.00 nM for the Kgp nanogels. Furthermore, they also showed excellent selectivity against bacterial culture supernatants E8 (Rgp knockout), K1A (Kgp knockout), and W50-d (wild-type) strains in complex medium of brain heart infusion (BHI).

In Vivo Identification of Thick, Thin, and Pale Stripes of Macaque Area V2 Using Submillimeter Resolution (f)MRI at 3 T.

Primate area V2 contains a repetitive pattern of thick, thin and pale cytochrome oxidase stripes that are characterized by largely discrete in- and output channels, as well as differences in function, and myelo- and cytoarchitecture. Stripes have been identified mainly using microscope-based imaging of tiny portions of superficially located V2, or by postmortem methods, hence, the quest for (quasi) noninvasive tools to study these mesoscale functional units. Only recently, stripe-like V2 patterns have been demonstrated in humans with high-field (functional) magnetic resonance imaging (f)MRI, but in both such studies only 2 stripe compartments could be identified. Although interstripe distances in monkeys are ~half of those in humans, we show that all 3 V2 stripe classes can be reliably separated using submillimeter (f)MRI (0.6 mm isotropic voxels) on regular 3 T scanners by combining contrast agents and implanted phased-array coils. Specifically, we show highly reproducible fMRI patterns, both within and across subjects, of color-selective thin and disparity-selective thick stripes. Furthermore, reliable MRI-based higher myelin-density was observed in pale stripes. Hence, this is the first study showing segregation of columns using (f)MRI-based methods in macaque cortex, which opens the possibility of studying these elementary building blocks of the visual system noninvasively on a large scale.

Acquisition and generalization of cough trigger beliefs in allergic rhinitis.

In allergic conditions, trigger identification is often inaccurate, and may be influenced by pre-existing beliefs. In this study, we investigated the acquisition and generalization of symptom trigger beliefs in individuals with allergic rhinitis (n = 24) and control participants (n = 24). In a lab-based trigger acquisition task, unique exemplars of two trigger categories were either paired with saline inhalation (CS- category) or citric acid inhalation (CS+ category). The next day, we tested recognition and symptom expectancy for CS category exemplars and exemplars of novel trigger categories. Participants acquired differential symptom expectancies for CS+ compared to CS- exemplars, with faster acquisition in participants with rhinitis. Differential symptom expectancies persisted the next day, and generalized to novel trigger categories, with stronger generalization in rhinitis vs. control participants. These patterns of acquisition and generalization suggest that overgeneralization of trigger beliefs may complicate trigger identification in participants with allergic conditions.

Towards an assessment of perceived COPD exacerbation triggers: Initial development and validation of a questionnaire.

BACKGROUND AND OBJECTIVE: Prevention of exacerbations in chronic obstructive pulmonary disease (COPD) is important to decrease overall declines in functioning and improve quality of life. The present study sought to develop a psychometrically valid measure of perceived triggers of exacerbations in COPD patients, the COPD Exacerbation Trigger Inventory (CETI). METHODS: Participants (n = 192) were recruited through local clinics and online to complete surveys of the CETI, demographic information, disease-specific information and the COPD Assessment Test (CAT). The CETI included a free response section on patients' individual top triggers, combined with ratings of their controllability. RESULTS: Exploratory principal component analyses identified a stable 5-factor structure (33 items), from which trigger subscales for weather/climate, air pollution/irritants, exercise, infection/illness and psychological factors were formed (internal consistency Cronbach's α = 0.90-0.94). Trigger factors were associated with COPD functional status, exacerbation frequency and healthcare utilization. Participants found personal triggers related to dust, air pollution, smoking and physical activity to be the most easily controlled, whereas those related to psychological factors, climate, infection, respiratory symptoms and sleep to be more difficult to control. Greater perceived controllability of triggers was associated with lower CAT scores, indicating better health status and less impact of the disease on functioning. CONCLUSION: The CETI is a psychometrically valid measure of perceived exacerbation triggers in patients with COPD. Perceived triggers are associated with clinical outcomes. Assessment of trigger classes and their controllability may prove useful in both research and clinical settings with COPD patients and to further our knowledge in prevention and disease management.

Covert shifts of spatial attention in the macaque monkey.

In the awake state, shifts of spatial attention alternate with periods of sustained attention at a fixed location or object. Human fMRI experiments revealed the critical role of the superior parietal lobule (SPL) in shifting spatial attention, a finding not predicted by human lesion studies and monkey electrophysiology. To investigate whether a potential homolog of the human SPL shifting region exists in monkeys (Macaca mulatta), we adopted an event-related fMRI paradigm that closely resembled a human experiment (Molenberghs et al., 2007). In this paradigm, a pair of relevant and irrelevant shapes was continuously present on the horizontal meridian. Subjects had to covertly detect a dimming of the relevant shape while ignoring the irrelevant dimmings. The events of interest consisted of the replacement of one stimulus pair by the next. During shift but not stay events, the relevant shape of the new pair appeared at the contralateral position relative to the previous one. Spatial shifting events activated parietal areas V6/V6A and medial intraparietal area, caudo-dorsal visual areas, the most posterior portion of the superior temporal sulcus, and several smaller frontal areas. These areas were not activated during passive stimulation with the same sensory stimuli. During stay events, strong direction-sensitive attention signals were observed in a distributed set of contralateral visual, temporal, parietal, and lateral prefrontal areas, the vast majority overlapping with the sensory stimulus representation. We suggest medial intraparietal area and V6/V6A as functional counterparts of human SPL because they contained the most widespread shift signals in the absence of contralateral stay activity, resembling the functional characteristics of the human SPL shifting area.

Probabilistic and single-subject retinotopic maps reveal the topographic organization of face patches in the macaque cortex.

Face perception is crucial to survival among social primates. It has been suggested that a group of extrastriate cortical regions responding more strongly to faces than to nonface objects is critical for face processing in primates. It is generally assumed that these regions are not retinotopically organized, as with human face-processing areas, showing foveal bias but lacking any organization with respect to polar angle. Despite many electrophysiological studies targeting monkey face patches, the retinotopic organization of these patches remains largely unclear. We have examined the relationship between cortical face patches and the topographic organization of extrastriate cortex using biologically relevant, phase-encoded retinotopic mapping stimuli in macaques. Single-subject fMRI results indicated a gradual shift from highly retinotopic to no topographic organization from posterior to anterior face patches in inferotemporal cortex. We also constructed a probabilistic retinotopic atlas of occipital and ventral extrastriate visual cortex. By comparing this probabilistic map to the locations of face patches at the group level, we showed that a previously identified posterior lateral temporal face patch (PL) is located within the posterior inferotemporal dorsal (PITd) retinotopic area. Furthermore, we identified a novel face patch posterior PL, which is located in retinotopically organized transitional area V4 (V4t). Previously published coordinates of human PITd coincide with the group-level occipital face area (OFA), according to a probabilistic map derived from a large population, implying a potential correspondence between monkey PL/PITd and human OFA/PITd. Furthermore, the monkey middle lateral temporal face patch (ML) shows consistent foveal biases but no obvious polar-angle structure. In contrast, middle fundus temporal (MF), anterior temporal and prefrontal monkey face patches lacked topographic organization.

The retinotopic organization of macaque occipitotemporal cortex anterior to V4 and caudoventral to the middle temporal (MT) cluster.

The retinotopic organization of macaque occipitotemporal cortex rostral to area V4 and caudorostral to the recently described middle temporal (MT) cluster of the monkey (Kolster et al., 2009) is not well established. The proposed number of areas within this region varies from one to four, underscoring the ambiguity concerning the functional organization in this region of extrastriate cortex. We used phase-encoded retinotopic functional MRI mapping methods to reveal the functional topography of this cortical domain. Polar-angle maps showed one complete hemifield representation bordering area V4 anteriorly, split into dorsal and ventral counterparts corresponding to the lower and upper visual field quadrants, respectively. The location of this hemifield representation corresponds to area V4A. More rostroventrally, we identified three other complete hemifield representations. Two of these correspond to the dorsal and the ventral posterior inferotemporal areas (PITd and PITv, respectively) as identified in the Felleman and Van Essen (1991) scheme. The third representation has been tentatively named dorsal occipitotemporal area (OTd). Areas V4A, PITd, PITv, and OTd share a central visual field representation, similar to the areas constituting the MT cluster. Furthermore, they vary widely in size and represent the complete contralateral visual field. Functionally, these four areas show little motion sensitivity, unlike those of the MT cluster, and two of them, OTd and PITd, displayed pronounced two-dimensional shape sensitivity. In general, these results suggest that retinotopically organized tissue extends farther into rostral occipitotemporal cortex of the monkey than generally assumed.

The impact of harmfulness information on citric acid induced cough and urge-to-cough.

PURPOSE: The cough reflex is an automatic protective reflex, which can be modulated by conscious effort or other forms of top-down control. In this experiment, we investigated whether information about harmfulness of a cough-inducing substance would augment cough reflex sensitivity and associated urge-to-cough. METHODS: Healthy participants (N = 39) were randomized to receive information that they were to inhale a harmless substance (natural citric acid), or a potentially harmful substance (a potent agro-chemical acid). Using dosimeter-controlled inhalations, the dose of citric acid eliciting at least three coughs (C3) was determined. Next, participants received 4 blocks of randomized presentations of citric acid at the C3 dose, a sub-threshold dose of citric acid and saline control. RESULTS: C3 was reached for 27/39 participants, and C3 thresholds were not influenced by harmfulness information. During repeated citric acid presentations, framing the cough-inducing substance as a potentially harmful chemical resulted in a greater urge-to-cough compared to information framing it as natural citric acid (p < .01). The experimental manipulation did not influence cough frequencies. CONCLUSIONS: Our findings show that harmfulness information influences urge-to-cough, corroborating the role of cortical mechanisms in modulating the urge-to-cough and suggesting that cognitive manipulations may contribute to cough treatment.

Surface based analysis of diffusion orientation for identifying architectonic domains in the in vivo human cortex.

Diffusion tensor MRI is sensitive to the coherent structure of brain tissue and is commonly used to study large-scale white matter structure. Diffusion in gray matter is more isotropic, however, several groups have observed coherent patterns of diffusion anisotropy within the cerebral cortical gray matter. We extend the study of cortical diffusion anisotropy by relating it to the local coordinate system of the folded cerebral cortex. We use 1mm and sub-millimeter isotropic resolution diffusion imaging to perform a laminar analysis of the principal diffusion orientation, fractional anisotropy, mean diffusivity and partial volume effects. Data from 6 in vivo human subjects, a fixed human brain specimen and an anesthetized macaque were examined. Large regions of cortex show a radial diffusion orientation. In vivo human and macaque data displayed a sharp transition from radial to tangential diffusion orientation at the border between primary motor and somatosensory cortex, and some evidence of tangential diffusion in secondary somatosensory cortex and primary auditory cortex. Ex vivo diffusion imaging in a human tissue sample showed some tangential diffusion orientation in S1 but mostly radial diffusion orientations in both M1 and S1.

A 22-channel receive array with Helmholtz transmit coil for anesthetized macaque MRI at 3 T.

The macaque monkey is an important model for cognitive and sensory neuroscience that has been used extensively in behavioral, electrophysiological, molecular and, more recently, neuroimaging studies. However, macaque MRI has unique technical differences relative to human MRI, such as the geometry of highly parallel receive arrays, which must be addressed to optimize imaging performance. A 22-channel receive coil array was constructed specifically for rapid high-resolution anesthetized macaque monkey MRI at 3 T. A local Helmholtz transmit coil was used for excitation. Signal-to-noise ratios (SNRs) and noise amplification for parallel imaging were compared with those of single- and four-channel receive coils routinely used for macaque MRI. The 22-channel coil yielded significant improvements in SNR throughout the brain. Using this coil, the SNR in peripheral brain was 2.4 and 1.7 times greater than that obtained with single- or four-channel coils, respectively. In the central brain, the SNR gain was 1.5 times that of both the single- and four-channel coils. Finally, the performance of the array for functional, anatomical and diffusion-weighted imaging was evaluated. For all three modalities, the use of the 22-channel array allowed for high-resolution and accelerated image acquisition.

Microcontact-Imprinted Optical Sensors for Virulence Factors of Periodontal Disease.

Periodontitis (gum disease) is a common biofilm-mediated oral condition, with around 7% of the adult population suffering from severe disease with risk for tooth loss. Moreover, periodontitis virulence markers have been found in atherosclerotic plaque and brain tissue, suggesting a link to cardiovascular and Alzheimer's diseases. The lack of accurate, fast, and sensitive clinical methods to identify patients at risk leads, on the one hand, to patients being undiagnosed until the onset of severe disease and, on the other hand, to overtreatment of individuals with mild disease, diverting resources from those patients most in need. The periodontitis-associated bacterium, Porphyromonas gingivalis, secrete gingipains which are highly active proteases recognized as key virulence factors during disease progression. This makes them interesting candidates as predictive biomarkers, but currently, there are no methods in clinical use for monitoring them. Quantifying the levels or proteolytic activity of gingipains in the periodontal pocket surrounding the teeth could enable early-stage disease diagnosis. Here, we report on a monitoring approach based on high-affinity microcontact imprinted polymer-based receptors for the Arg and Lys specific gingipains Rgp and Kgp and their combination with surface plasmon resonance (SPR)-based biosensor technology for quantifying gingipain levels in biofluids and patient samples. Therefore, Rgp and Kgp were immobilized on glass coverslips followed by microcontact imprinting of poly-acrylamide based films anchored to gold sensor chips. The monomers selected were N-isopropyl acrylamide (NIPAM), N-hydroxyethyl acrylamide (HEAA) and N-methacryloyl-4-aminobenzamidine hydrochloride (BAM), with N,N'-methylene bis(acrylamide) (BIS) as the crosslinker. This resulted in imprinted surfaces exhibiting selectivity towards their templates high affinity and selectivity for the templated proteins with dissociation constants (K d) of 159 and 299 nM for the Rgp- and Kgp-imprinted, surfaces respectively. The former surface displayed even higher affinity (K d = 71 nM) when tested in dilute cell culture supernatants. Calculated limits of detection for the sensors were 110 and 90 nM corresponding to levels below clinically relevant concentrations.

Symptoms, lung function, and perception of asthma control: an exploration into the heterogeneity of the asthma control construct.

BACKGROUND: Asthma control is still surprisingly poor, which may be related to factors causing discrepancies between objective lung function measures and subjective symptom reports or discrepancies between objective indicators of asthma control and control perception. Identifying patients prone to such discrepancies may help to understand asthma control problems. METHODS: Ninety-four persons with asthma participated in this study. We used cluster analysis to identify different subgroups of asthma control, based on a measure of lung function and self-report of daytime and nighttime symptoms, activity limitations, reliever medication use, and perception of asthma control. Subsequently, we explored between-cluster differences in clinical and psychological characteristics. RESULTS: We identified two homogeneous clusters: a cluster of persons with poorly controlled asthma and a cluster of persons with well-controlled asthma. A third cluster included persons with an intermediate level of asthma control, an absence of nighttime symptoms, and a reduced impact of asthma symptoms on daily activities despite high levels of symptoms and reliever medication use. Members of the poorly controlled asthma cluster showed higher symptom levels, more catastrophic thinking, and activity avoidance beliefs compared with members of other clusters. CONCLUSION: The clusters we identified crosscut current definitions of asthma severity and asthma control and indicate the importance of affective evaluation of symptoms in explaining poor asthma control.

Predicting asthma treatment outcome at diagnosis: the role of symptom perception during a histamine challenge test.

OBJECTIVE: In asthma, many treatment decisions are dependent upon patient perception/patient report of asthma symptoms. Discrepancies between patient perception of asthma symptoms and objective indicators of pathophysiology are widespread and can hinder asthma treatment. Early detection of problems in asthma symptom perception may be a first step to help these patients. We investigated the predictive value of symptom perception during a histamine challenge test (HCT) at asthma diagnosis for patient-rated outcome of asthma treatment 3 months later. METHODS: In a prospective observational study, persons with asthma (N = 60) showing bronchial hyperresponsiveness in a HCT completed questions on asthma symptoms and negative affectivity (NA). The HCT was extended with an ambiguous situation suggesting asthma symptoms despite physiological recovery. Lung function (forced expiratory volume in 1 second (FEV(1))) and symptom ratings were measured during the test (after each histamine dosage), and we constructed several measures of asthma symptom perception based on FEV(1) and symptom ratings. Three months later, 30 participants completed questionnaires on asthma control and asthma-related quality of life. RESULTS: Symptoms reported during HCT predicted worse asthma control and quality of life 3 months later. The prospective association between symptoms during HCT and asthma control remained significant when controlling for NA and baseline lung function. These effects were strongest for symptoms during ambiguous situations. CONCLUSIONS: Higher symptom levels at the start of the HCT and during recovery may reflect a tendency to inaccurately perceive asthma symptoms in ambiguous situations. Assessing symptoms during diagnostic challenge tests can help predict problems with asthma treatment.

ERS International Congress 2021: highlights from the Allied Respiratory Professionals assembly.

This paper provides an overview of some of the most memorable sessions that were (co)organised by the Allied Respiratory Professionals Assembly during the 2021 European Respiratory Society International Congress, which was held online for the second consecutive year due to the COVID-19 pandemic. Early Career Members from Assembly 9 summarised the content of the sessions (three oral communication sessions, two symposia and one Expert View) with the support of the chairs from the four Assembly groups: Respiratory Function Technologists and Scientists (Group 9.01); Physiotherapists (Group 9.02); Nurses (Group 9.03); and Psychologists and Behavioural Scientists (Group 9.04). The sessions covered the following topics: impact of COVID-19 on lung function and healthcare services, and the importance of quality assurance and technology in lung function assessment; diagnosis and management of sarcopenia in patients with chronic respiratory disease; maintenance of the effects of pulmonary rehabilitation; solutions outside the hospital for the management of patients with COVID-19 in need of health care; the nursing perspective during the COVID-19 pandemic; and psychological and behavioural issues in respiratory care. This highlights article provides valuable insight into the latest scientific data and emerging areas affecting clinical practice of allied respiratory professionals.

Dyspnea-related anxiety: The Dutch version of the Breathlessness Beliefs Questionnaire.

Dyspnea-related anxiety may lead to reduced quality of life and functional disability through fearful avoidance of dyspnea-evoking activity. We describe the validation of a generic - diagnosis-independent - instrument assessing dyspnea-related anxiety. A total of 187 patients with respiratory diseases completed the Breathlessness Beliefs Questionnaire (BBQ), a 17-item questionnaire adapted from the Tampa Scale for Kinesiophobia (TSK), a measure of how harmful pain patients think painful movement is and to what extent they think activity should be avoided. Measures of negative and positive affectivity (PANAS), anxiety and depression (HADS), functional status (PFSDQ), and health-related quality of life (CRDQ) were also completed. Principal component analysis and item-total correlations suggested a reliable (reduced) 11-item BBQ (Cronbach's alpha = .85) with two factors converging with the TSK factors: a 'somatic focus' factor assessing the harmfulness of dyspnea and the underlying pathology and an 'activity avoidance' factor assessing beliefs that activity should be avoided. Correlational analyses support the construct validity of the BBQ: higher scores on the BBQ are associated with reduced health-related quality of life and functional status. Associations between 'somatic focus' and negative affectivity and anxiety and between 'activity avoidance' and positive affectivity and depression further supported the validity of the BBQ and its subscales. The BBQ is a valid, short, and useful instrument to assess respiratory patients' beliefs about the harmfulness of their disease and physical activities. Further research is needed to document to what extent BBQ scores are related to daily life activities and symptoms.

Subcortical gray matter volumes in asthma: associations with asthma duration, control, and anxiety.

Asthma as a chronic inflammatory disease can be expected to affect central nervous system structures but little is known about subcortical structures in asthma and their potential association with illness-specific outcomes and anxiety. A total of 40 young adults (20 with asthma and 20 gender- and age-matched controls) underwent high-resolution T1-weighted MRI scan, viewed short distressing film clips, and filled in questionnaires about anxious and depressed mood, as well as asthma history, control, and catastrophizing thoughts about asthma, for those with asthma. The structural scans were processed in FSL's FIRST program to delineate subcortical structures of interest: amygdala, hippocampus, putamen, pallidum, caudate nucleus, nucleus accumbens, and thalamus. Findings showed no general reduction in subcortical gray matter volumes in asthma compared to controls. Asthma duration, asthma control, and catastrophizing of asthma and asthma attacks were negatively associated with volumes of putamen and pallidum, and to a weaker extent thalamus and amygdala, while controlling for gender, age, and corticosteroid inhaler use. In addition, stronger anxiety in response to distressing films was associated with lower volume of the pallidum, whereas general anxious and depressed mood was unrelated to subcortical structures. Thus, although there are no subcortical structural differences between young adults with asthma and healthy controls, longer asthma history, suboptimal management, and illness-related anxiety are reflected in lower gray matter volumes of subcortical structures, further emphasizing the importance of maintaining optimal asthma control.

In the spotlight: first ERS Early Career Member Award winner, the ERS Lung Science Conference 2020 and new ECMC members.

All you need to know about @LiesLahousse, first ECM to be granted the Early Career Member Award; #LSC2020; the newly elected assembly representatives for @EarlyCareerERS; and new @EuroRespSoc fellowship opportunities http://bit.ly/2OTgQlo.

Placebo and nocebo effects and operant pain-related avoidance learning.

INTRODUCTION: Research on learning in placebo and nocebo has relied predominantly on Pavlovian conditioning procedures. Operant learning procedures may more accurately model learning in real-life situations in which placebo and nocebo effects occur. OBJECTIVES: To investigate the development and persistence of placebo and nocebo effects using an operant avoidance learning task. METHODS: Pain-free participants (n = 58) could learn to avoid pain by performing movements that differed in difficulty and intensity of painful stimulation. Participants performed movements in 2 contexts. In the high cost of avoidance context, pain stimulus intensity reduced with increasing movement difficulty. In the low cost of avoidance context, contingencies were reversed. Participants rated pain expectations and pain intensity. During test, movement difficulties were unchanged, but participants always received a medium-intensity pain stimulus. Placebo and nocebo effects were defined as lower/higher pain intensity ratings for trajectories that previously resulted in low/high-intensity compared with medium-intensity stimulation. RESULTS: As expected, participants acquired differential movement-pain expectations and differential movement choices. Testing with a medium-intensity pain stimulus quickly erased differences in movement choice across contexts, but differences in pain expectations were maintained. Pain modulation across context was in line with movement-pain expectations. However, we only observed placebo effects within the low cost of avoidance context and found no evidence of nocebo effects. CONCLUSION: Operant learning can change pain expectations, pain modulation, and pain-related avoidance behavior. Persisting pain expectations suggest that acquired pain beliefs may be resistant to disconfirmation, despite self-initiated experience with novel pain-movement contingencies.

Assessment of Anterior Cruciate Ligament Graft Maturity With Conventional Magnetic Resonance Imaging: A Systematic Literature Review.

BACKGROUND: Magnetic resonance imaging (MRI) signal intensity (SI) measurements are being used increasingly in both clinical and research studies to assess the maturity of anterior cruciate ligament (ACL) grafts in humans. However, SI in conventional MRI with weighted images is a nonquantitative measure dependent on hardware and software. PURPOSE: To conduct a systematic review of studies that have used MRI SI as a proxy for ACL graft maturity and to identify potential confounding factors in assessing the ACL graft in conventional MRI studies. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review was conducted by searching the MEDLINE/PubMed, Scopus, and Cochrane Library electronic databases according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify studies that examined the healing of the intra-articular portion of the ACL graft by assessing SI on MRIs. RESULTS: A total of 34 studies were selected for inclusion in this systematic review. The MRI acquisition techniques and methods to evaluate the ACL graft SI differed greatly across the studies. No agreement was found regarding the time frames of SI changes in MRI reflecting normal healing of the ACL tendon graft, and the graft SI and clinical outcomes after ACL reconstruction were found to be poorly correlated. CONCLUSION: The MRI acquisition and evaluation methods used to assess ACL grafts are very heterogeneous, impeding comparisons of SI between successive scans and between independent studies. Therefore, quantitative MRI-based biomarkers of ACL graft healing are greatly needed to guide the appropriate time of returning to sports after ACL reconstruction.

Impact of Disease-Specific Fears on Pulmonary Rehabilitation Trajectories in Patients with COPD.

Disease-specific fears predict health status in chronic obstructive pulmonary disease (COPD), but their role in pulmonary rehabilitation (PR) remains poorly understood and especially longer-term evaluations are lacking. We therefore investigated changes in disease-specific fears over the course of PR and six months after PR, and investigated associations with PR outcomes (COPD assessment test (CAT) and St. Georges respiratory questionnaire (SGRQ)) in a subset of patients with COPD (n = 146) undergoing a 3-week inpatient PR program as part of the STAR study (Clinicaltrials.gov, ID: NCT02966561). Disease-specific fears as measured with the COPD anxiety questionnaire improved after PR. For fear of dyspnea, fear of physical activity and fear of disease progression, improvements remained significant at six-month follow-up. Patients with higher disease-specific fears at baseline showed elevated symptom burden (CAT and SGRQ Symptom scores), which persisted after PR and at follow-up. Elevated disease-specific fears also resulted in reduced improvements in Quality of Life (SGRQ activity and impact scales) after PR and at follow-up. Finally, improvement in disease-specific fears was associated with improvement in symptom burden and quality of life. Adjustment for potential confounding variables (sex, smoking status, age, lung function, and depressive symptoms) resulted in comparable effects. These findings show the role of disease-specific fears in patients with COPD during PR and highlight the need to target disease-specific fears to further improve the effects of PR.