No evidence that arousal affects reactivated memories.

Memory for inherently neutral elements of emotional events is often enhanced on delayed tests - an effect that has been attributed to noradrenergic arousal. Reactivation of a memory is thought to return its corresponding neural ensemble to a state that is similar to when it was originally experienced. Therefore, we hypothesized that neutral elements of memories, too, can be enhanced through reactivation concurrent with heightened arousal. Participants (n = 94) visited the lab for three sessions. During the first session, they encoded 120 neutral memories consisting of an object presented in unique context images. In session two, the 80 objects were reactivated by presenting their corresponding context images, 40 of which were immediately followed by an arousal-inducing shock. Finally, recognition memory for all objects was tested. It was found that memory for reactivated objects was enhanced, but even though the shocks elicited elevations in arousal as indexed by skin conductance, there was no difference between memory of objects reactivated with and without heightened arousal. We thus conclude that arousal, when isolated from other cognitive and affective variables that might impact memory, has no enhancing effect on reactivated memories.

Reliability and Accuracy of the Pediatric Swiss Emergency Triage Scale-the SETSped Study.

BACKGROUND AND IMPORTANCE: The Swiss Emergency Triage Scale (SETS) is an adult triage tool used in several emergency departments. It has been recently adapted to the pediatric population but, before advocating for its use, performance assessment of this tool is needed. OBJECTIVES: The purpose of this study was to assess the reliability and the accuracy of the pediatric version of the SETS for the triage of pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: This study was a cross-sectional study among a sample of emergency triage nurses (ETNs) exposed to 17 clinical scenarios using a computerized simulator. OUTCOME MEASURES AND ANALYSIS: The primary outcome was the reliability of the triage level performed by the ETNs. It was assessed using an intraclass correlation coefficient.Secondary outcomes included accuracy of triage compared with expert-based triage levels and factors associated with accurate triage. MAIN RESULTS: Eighteen ETNs participated in the study and completed the evaluation of all scenarios, for a total of 306 triage decisions. The intraclass correlation coefficient was 0.80 (95% confidence interval, 0.69-0.91), with an agreement by scenario ranging from 61.1% to 100%. The overall accuracy was 85.8%, and nurses were more likely to undertriage (16.0%) than to overtriage (4.3%). No factor for accurate triage was identified. CONCLUSIONS: This simulator-based study showed that the SETS is reliable and accurate among a pediatric population. Future research is needed to confirm these results, compare this triage scale head-to-head with other recognized international tools, and study the SETSped in real-life setting.

Identifying individual, household and environmental risk factors for malaria infection on Bioko Island to inform interventions.

BACKGROUND: Since 2004, malaria transmission on Bioko Island has declined significantly as a result of the scaling-up of control interventions. The aim of eliminating malaria from the Island remains elusive, however, underscoring the need to adapt control to the local context. Understanding the factors driving the risk of malaria infection is critical to inform optimal suits of interventions in this adaptive approach. METHODS: This study used individual and household-level data from the 2015 and 2018 annual malaria indicator surveys on Bioko Island, as well as remotely-sensed environmental data in multilevel logistic regression models to quantify the odds of malaria infection. The analyses were stratified by urban and rural settings and by survey year. RESULTS: Malaria prevalence was higher in 10-14-year-old children and similar between female and male individuals. After adjusting for demographic factors and other covariates, many of the variables investigated showed no significant association with malaria infection. The factor most strongly associated was history of travel to mainland Equatorial Guinea (mEG), which increased the odds significantly both in urban and rural settings (people who travelled had 4 times the odds of infection). Sleeping under a long-lasting insecticidal net decreased significantly the odds of malaria across urban and rural settings and survey years (net users had around 30% less odds of infection), highlighting their contribution to malaria control on the Island. Improved housing conditions indicated some protection, though this was not consistent across settings and survey year. CONCLUSIONS: Malaria risk on Bioko Island is heterogeneous and determined by a combination of factors interacting with local mosquito ecology. These interactions grant further investigation in order to better adapt control according to need. The single most important risk factor identified was travel to mEG, in line with previous investigations, and represents a great challenge for the success of malaria control on the Island.

Assessing IRS performance in a gender-integrated vector control programme on Bioko Island, Equatorial Guinea, 2010-2021.

BACKGROUND: Indoor residual spraying (IRS) is a common vector control strategy in countries with high malaria burden. Historically, social norms have prevented women from working in IRS programmes. The Bioko Island Malaria Elimination Project has actively sought to reduce gender inequality in malaria control operations for many years by promoting women's participation in IRS. METHODS: This study investigated the progress of female engagement and compared spray productivity by gender from 2010 to 2021, using inferential tests and multivariable regression. Spray productivity was measured by rooms sprayed by spray operator per day (RSOD), houses sprayed by spray operator per day (HSOD), and the daily productivity ratio (DPR), defined as the ratio of RSOD to HSOD, which standardized productivity by house size. RESULTS: The percentage of women participating in IRS has increased over time. The difference in DPR comparing male and female spray operators was only statistically significant (p < 0.05) for two rounds, where the value was higher for women compared to men. Regression analyses showed marginal, significant differences in DPR between men and women, but beta coefficients were extremely small and thus not indicative of a measurable effect of gender on operational performance. CONCLUSIONS: The quantitative analyses of spray productivity are counter to stigmatizing beliefs that women are less capable than male counterparts during IRS spray rounds. The findings from this research support the participation of women in IRS campaigns, and a renewed effort to implement equitable policies and practices that intentionally engage women in vector control activities.

Lung-on-a-Chip Models of the Lung Parenchyma.

Since the publication of the first lung-on-a-chip in 2010, research has made tremendous progress in mimicking the cellular environment of healthy and diseased alveoli. As the first lung-on-a-chip products have recently reached the market, innovative solutions to even better mimic the alveolar barrier are paving the way for the next generation lung-on-chips. The original polymeric membranes made of PDMS are being replaced by hydrogel membranes made of proteins from the lung extracellular matrix, whose chemical and physical properties exceed those of the original membranes. Other aspects of the alveolar environment are replicated, such as the size of the alveoli, their three-dimensional structure, and their arrangement. By tuning the properties of this environment, the phenotype of alveolar cells can be tuned, and the functions of the air-blood barrier can be reproduced, allowing complex biological processes to be mimicked. Lung-on-a-chip technologies also provide the possibility of obtaining biological information that was not possible with conventional in vitro systems. Pulmonary edema leaking through a damaged alveolar barrier and barrier stiffening due to excessive accumulation of extracellular matrix proteins can now be reproduced. Provided that the challenges of this young technology are overcome, there is no doubt that many application areas will benefit greatly.

Autologous tumor lysate-loaded dendritic cell vaccination in glioblastoma: What happened to the evidence?

In patients with glioblastoma, the "DCVax-L" trial reported a survival benefit with the addition of autologous tumor lysate-loaded denditric cell vaccination to the standard-of-care (SoC) in patients with glioblastoma. The trial presented as a phase 3 externally controlled trial is showing an improvement in overall survival (OS) in patients receiving the vaccine therapy as compared to externally controlled patients, both in the newly diagnosed setting (median OS = 19.3 months versus 16.5 months; HR = 0.80; 98% CI, 0.00-0.94; P = 0.002) and in the recurrent setting (median OS = 13.2 months versus 7.8 months; HR = 0.58; 98% CI, 0.00-0.76; P < 0.001). Interestingly, the original endpoint, progression-free survival (PFS), was not improved by the experimental therapy. While we praise efforts to improve outcomes in a population representing a true unmet need, the trial's design, methods and report raise several issues undermining the ability to derive meaningful conclusion. These limitations are mainly driven by multiple changes occurring years after the trial ended. External controls were used in a trial originally randomizing patients, the primary endpoint was modified (OS instead of PFS), a new study population (recurrent glioblastoma) was added, and unplanned analyses were conducted, among several other changes. Additionally, due to inclusion criteria, the external controls likely selected patients with less favorable outcome as compared with patients enrolled in the trial, potentially biasing the reported survival benefit. In the absence of data sharing, these shortcomings will not be clarified. Dendritic cell vaccination remains a promising approach for GBM. It is therefore disappointing that due to key methodological limitations, the DCVax-L trial ultimately failed to provide sound conclusions about the potential efficacy of such approach for patients with glioblastoma.

Paediatric Burkitt lymphoma patient-derived xenografts capture disease characteristics over time and are a model for therapy.

Burkitt lymphoma (BL) accounts for almost two-thirds of all B-cell non-Hodgkin lymphoma (B-NHL) in children and adolescents and is characterised by a MYC translocation and rapid cell turnover. Intensive chemotherapeutic regimens have been developed in recent decades, including the lymphomes malins B (LMB) protocol, which have resulted in a survival rate in excess of 90%. Recent clinical trials have focused on immunochemotherapy, with the addition of rituximab to chemotherapeutic backbones, showing encouraging results. Despite these advances, relapse and refractory disease occurs in up to 10% of patients and salvage options for these carry a dismal prognosis. Efforts to better understand the molecular and functional characteristics driving relapse and refractory disease may help improve this prognosis. This study has established a paediatric BL patient-derived xenograft (PDX) resource which captures and maintains tumour heterogeneity, may be used to better characterise tumours and identify cell populations responsible for therapy resistance.

CD90+CD146+ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung.

Our understanding of mesenchymal cell subsets and their function in human lung affected by aging and in certain disease settings remains poorly described. We use a combination of flow cytometry, prospective cell-sorting strategies, confocal imaging, and modeling of microvessel formation using advanced microfluidic chip technology to characterize mesenchymal cell subtypes in human postnatal and adult lung. Tissue was obtained from patients undergoing elective surgery for congenital pulmonary airway malformations (CPAM) and other airway abnormalities including chronic obstructive pulmonary disease (COPD). In microscopically normal postnatal human lung, there was a fivefold higher mesenchymal compared with epithelial (EpCAM+) fraction, which diminished with age. The mesenchymal fraction composed of CD90+ and CD90+CD73+ cells was enriched in CXCL12 and platelet-derived growth factor receptor-α (PDGFRα) and located in close proximity to EpCAM+ cells in the alveolar region. Surprisingly, alveolar organoids generated from EpCAM+ cells supported by CD90+ subset were immature and displayed dysplastic features. In congenital lung lesions, cystic air spaces and dysplastic alveolar regions were marked with an underlying thick interstitium composed of CD90+ and CD90+PDGFRα+ cells. In postnatal lung, a subset of CD90+ cells coexpresses the pericyte marker CD146 and supports self-assembly of perfusable microvessels. CD90+CD146+ cells from COPD patients fail to support microvessel formation due to fibrinolysis. Targeting the plasmin-plasminogen system during microvessel self-assembly prevented fibrin gel degradation, but microvessels were narrower and excessive contraction blocked perfusion. These data provide important new information regarding the immunophenotypic identity of key mesenchymal lineages and their change in a diverse setting of congenital lung lesions and COPD.

Integrated omics profiling reveals novel patterns of epigenetic programming in cancer-associated myofibroblasts.

There is increasing evidence that stromal myofibroblasts play a key role in the tumour development however, the mechanisms by which they become reprogrammed to assist in cancer progression remain unclear. As cultured cancer-associated myofibroblasts (CAMs) retain an ability to enhance the proliferation and migration of cancer cells in vitro, it is possible that epigenetic reprogramming of CAMs within the tumour microenvironment may confer long-term pro-tumourigenic changes in gene expression. This study reports the first comparative multi-omics analysis of cancer-related changes in gene expression and DNA methylation in primary myofibroblasts derived from gastric and oesophageal tumours. In addition, we identify novel CAM-specific DNA methylation signatures, which are not observed in patient-matched adjacent tissue-derived myofibroblasts, or corresponding normal tissue-derived myofibroblasts. Analysis of correlated changes in DNA methylation and gene expression shows that different patterns of gene-specific DNA methylation have the potential to confer pro-tumourigenic changes in metabolism, cell signalling and differential responses to hypoxia. These molecular signatures provide new insights into potential mechanisms of stromal reprogramming in gastric and oesophageal cancer, while also providing a new resource to facilitate biomarker identification and future hypothesis-driven studies into mechanisms of stromal reprogramming and tumour progression in solid tumours.

A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA.

BACKGROUND: The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. The development of an effective Ebola vaccine is a priority for control of a future outbreak. METHODS: In this phase 1 study, we administered a single dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) to 60 healthy adult volunteers in Oxford, United Kingdom. The vaccine was administered in three dose levels--1×10(10) viral particles, 2.5×10(10) viral particles, and 5×10(10) viral particles--with 20 participants in each group. We then assessed the effect of adding a booster dose of a modified vaccinia Ankara (MVA) strain, encoding the same Ebola virus glycoprotein, in 30 of the 60 participants and evaluated a reduced prime-boost interval in another 16 participants. We also compared antibody responses to inactivated whole Ebola virus virions and neutralizing antibody activity with those observed in phase 1 studies of a recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) to determine relative potency and assess durability. RESULTS: No safety concerns were identified at any of the dose levels studied. Four weeks after immunization with the ChAd3 vaccine, ZEBOV-specific antibody responses were similar to those induced by rVSV-ZEBOV vaccination, with a geometric mean titer of 752 and 921, respectively. ZEBOV neutralization activity was also similar with the two vaccines (geometric mean titer, 14.9 and 22.2, respectively). Boosting with the MVA vector increased virus-specific antibodies by a factor of 12 (geometric mean titer, 9007) and increased glycoprotein-specific CD8+ T cells by a factor of 5. Significant increases in neutralizing antibodies were seen after boosting in all 30 participants (geometric mean titer, 139; P<0.001). Virus-specific antibody responses in participants primed with ChAd3 remained positive 6 months after vaccination (geometric mean titer, 758) but were significantly higher in those who had received the MVA booster (geometric mean titer, 1750; P<0.001). CONCLUSIONS: The ChAd3 vaccine boosted with MVA elicited B-cell and T-cell immune responses to ZEBOV that were superior to those induced by the ChAd3 vaccine alone. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT02240875.).

Suspicion of appendicitis in pregnant women: emergency evaluation by sonography and low-dose CT with oral contrast.

OBJECTIVES: To evaluate non-intravenously enhanced low-dose computed tomography with oral contrast (LDCT) for the assessment of pregnant women with right lower quadrant pain, when magnetic resonance imaging (MRI) is not immediately available. METHODS: One hundred and thirty-eight consecutive pregnant women with acute abdominal pain were admitted in our emergency centre. Thirty-seven (27%) of them, with clinical suspicion of acute appendicitis, underwent abdominal ultrasonography (US). No further examination was recommended when US was positive for appendicitis, negative with low clinical suspicion or showed an alternative diagnosis which explained the clinical presentation. All other patients underwent LDCT (<2.5 mSv). Standard intravenously enhanced CT or MRI was performed when LDCT was indeterminate. RESULTS: Eight (22%) of 37 US exams were reported normal, 25 (67%) indeterminate, 1 (3%) positive for appendicitis, 3 (8%) positive for an alternative diagnosis. LDCT was obtained in 29 (78%) patients. It was reported positive for appendicitis in 9 (31%), for alternative diagnosis in 2 (7%), normal in 13 (45%) and indeterminate in 5 (17%). Further imaging (standard CT or MRI) showed appendicitis in 2 of these 5 patients, was truly negative in 1, indeterminate in 1 and falsely positive in 1. An appendicitis was confirmed at surgery in 12 (32%) of the 37 patients. The sensitivity and the specificity of the algorithm for appendicitis were 100% (12/12) and 92% (23/25), respectively. CONCLUSIONS: The proposed algorithm is very sensitive and specific for detection of acute appendicitis in pregnant women; it reduces the need of standard CTs when MRI is not available as second-line imaging. KEY POINTS: • In pregnant women, US is limited by an important number of indeterminate results • Low-dose CT can be used after an inconclusive US for the diagnosis of appendicitis in pregnant women • An algorithm integrating US and low-dose CT is highly sensitive and specific for appendicitis in pregnant women.

Overuse of plain abdominal radiography in emergency departments: a retrospective cohort study.

BACKGROUND: Plain abdominal radiography (PAR) is routinely performed in emergency departments (EDs). This study aimed to (1) identify the indications for PAR in EDs and compare them against international guidelines, (2) uncover predictors of non-compliance with guidelines, and (3) describe the use of additional radiological examinations in EDs. METHODS: Retrospective cohort study in the EDs of two hospitals in Geneva, Switzerland, including all adult patients who underwent PAR in the EDs. Indications were considered "appropriate" if complying with guidelines. Predictors of non-compliance were identified by univariate and multivariate analyses. RESULTS: Over 1 year, PAR was performed in 1997 patients (2.2% of all admissions). Their mean age was 59.7 years, with 53.1% of female patients. The most common indications were constipation (30.8%), suspected ileus (28.9%), and abdominal pain (15.3%). According to the French and American guidelines, only 11.8% of the PARs were indicated, while 46.2% of them complied with the Australian and British guidelines. On multivariate analysis, admission to the private hospital ED (odds ratio [OR] 3.88, 95% CI 1.78-8.45), female gender (OR 1.95, 95% CI 1.46-2.59), and an age >  65 years (OR 2.41, 95%CI 1.74-3.32) were associated with a higher risk of inappropriate PAR. Additional radiological examinations were performed in 73.7% of patients. CONCLUSIONS: Most indications for PAR did not comply with guidelines and elderly women appeared particularly at risk of being exposed to inappropriate examination. PAR did not prevent the need for additional examinations. Local guidelines should be developed, and initiatives should be implemented to reduce unnecessary PARs. TRIAL REGISTRATION: ClinicalTrials.gov , identifier NCT02980081 .

Diagnosis of Pulmonary Embolism During Pregnancy: A Multicenter Prospective Management Outcome Study.

Background: Data on the optimal diagnostic management of pregnant women with suspected pulmonary embolism (PE) are limited, and guidelines provide inconsistent recommendations on use of diagnostic tests. Objective: To prospectively validate a diagnostic strategy in pregnant women with suspected PE. Design: Multicenter, multinational, prospective diagnostic management outcome study involving pretest clinical probability assessment, high-sensitivity D-dimer testing, bilateral lower limb compression ultrasonography (CUS), and computed tomography pulmonary angiography (CTPA). (ClinicalTrials.gov: NCT00740454). Setting: 11 centers in France and Switzerland between August 2008 and July 2016. Patients: Pregnant women with clinically suspected PE in emergency departments. Intervention: Pulmonary embolism was excluded in patients with a low or intermediate pretest clinical probability and a negative D-dimer result. All others underwent lower limb CUS and, if results were negative, CTPA. A ventilation-perfusion (V/Q) scan was done if CTPA results were inconclusive. Pulmonary embolism was excluded if results of the diagnostic work-up were negative, and untreated pregnant women had clinical follow-up at 3 months. Measurements: The primary outcome was the rate of adjudicated venous thromboembolic events during the 3-month follow-up. Results: 441 women were assessed for eligibility, and 395 were included in the study. Among these, PE was diagnosed in 28 (7.1%) (proximal deep venous thrombosis found on ultrasonography [n = 7], positive CTPA result [n = 19], and high-probability V/Q scan [n = 2]) and excluded in 367 (clinical probability and negative D-dimer result [n = 46], negative CTPA result [n = 290], normal or low-probability V/Q scan [n = 17], and other reason [n = 14]). Twenty-two women received extended anticoagulation during follow-up, mainly for previous venous thromboembolic disease. The rate of symptomatic venous thromboembolic events was 0.0% (95% CI, 0.0% to 1.0%) among untreated women after exclusion of PE on the basis of negative results on the diagnostic work-up. Limitation: There were several protocol deviations, reflecting the difficulty of performing studies in pregnant women with suspected PE. Conclusion: A diagnostic strategy based on assessment of clinical probability, D-dimer measurement, CUS, and CTPA can safely rule out PE in pregnant women. Primary Funding Source: Swiss National Foundation for Scientific Research, Groupe d'Etude de la Thrombose de Bretagne Occidentale, and International Society on Thrombosis and Haemostasis.

Femoral head subchondral impaction on CT: what does it mean in patients with acetabular fracture?

OBJECTIVE: To evaluate the prevalence of isolated femoral head impactions associated with acetabular fractures and to assess whether impactions may be predictive of the development of delayed major complications requiring total hip arthroplasty. MATERIALS AND METHODS: A total of 128 consecutive adult patients with acetabular fracture and no femoral head fracture were included. Admission CTs were re-interpreted for the presence of hip dislocation and femoral head impactions. Radiological and clinical reports were reviewed in patients in whom conservative management of the femoral head was attempted, to determine if total hip arthroplasty was eventually required over a 48-month follow-up period. Univariate and multivariate analyses were performed to assess whether impaction is an independent predictor of failure of conservative management. RESULTS: Impaction was found in 40% of all patients (51 out of 128), in 58% of those with dislocation (19 out of 33), and in 34% of those without dislocation (32 out of 95; p < 0.05). One hundred and five patients underwent conservative management of the femoral head; 12.5% of them (13 out of 105) eventually required total hip arthroplasty. An impaction was present in 77% of the latter (10 out of 13) and in 33% of patients with successful conservative management (30 out of 92; p = 0.0042). At multivariate analysis, impaction and dislocation were significantly and independently associated with a higher risk for delayed total hip arthroplasty (odds ratio of 4.8 and 4.0 respectively). CONCLUSION: Femoral head impactions are frequently seen on CT of patients with acetabular fractures; they are independent predictive factors for the need for delayed total hip arthroplasty. They should be systematically mentioned in the CT report.

Concomitant leukocytosis and lymphopenia predict significant pathology at CT of acute abdomen: a case-control study.

BACKGROUND: Acute abdominal pain accounts for about 10% of emergency department visits and has progressively become the primary indication for CT scanning in most centers. The goal of our study is to identify biological or clinical variables able to predict or rule out significant pathology (conditions requiring urgent medical or surgical treatment) on abdominal CT in patients presenting to an emergency department with acute abdominal pain. METHODS: This was a retrospective cohort study performed in the emergency department of an academic center with an annual census of 60'000 patients. One hundred and-nine consecutive patients presenting with an acute non-traumatic abdominal pain, not suspected of appendicitis or renal colic, during the first semester of 2013, who underwent an abdominal CT were included. Two medical students, completing their last year of medical school, extracted the data from patients' electronic health record. Ambiguities in the formulations of clinical symptoms and signs in the patients' records were solved by consulting a board certified emergency physician. Nine clinical and biological variables were extracted: shock index, peritonism, abnormal bowel sounds, fever (> 38 °C), intensity and duration of the pain, leukocytosis (white blood cell count >11G/L), relative lymphopenia (< 15% of total leukocytes), and C-reactive Protein (CRP). These variables were compared to the CT results (reference standard) to determine their ability to predict a significant pathology. RESULTS: Significant pathology was detected on CT in 71 (65%) patients. Only leukocytosis (odds ratio 3.3, p = 0.008) and relative lymphopenia (odds ratio 3.8, p = 0.002) were associated with significant pathology on CT. The joint presence of these two anomalies was strongly associated with significant pathology on CT (odds ratio 8.2, p = 0.033). Leukocytosis with relative lymphopenia had a specificity of 89% (33/37) and sensitivity of 48% (33/69) for the detection of significant pathology on CT. CONCLUSION: The high specificity of the association between leukocytosis and relative lymphopenia amongst the study population suggests that these parameters would be sufficient to justify an emergency CT. However, none of the parameters could be used to rule out a significant pathology.

Human microvasculature-on-a chip: anti-neovasculogenic effect of nintedanib in vitro.

Idiopathic pulmonary fibrosis is characterized by a progressive scarring and stiffening of the peripheral lung tissue that decreases lung function. Over the course of the disease, the lung microvasculature undergoes extensive remodeling. There is increased angiogenesis around fibrotic foci and an absence of microvessels within the foci. To elucidate how the anti-fibrotic drug nintedanib acts on vascular remodeling, we used an in vitro model of perfusable microvessels made with primary endothelial cells and primary lung fibroblasts in a microfluidic chip. The microvasculature model allowed us to study the impact of nintedanib on permeability, vascularized area, and cell-cell interactions. The anti-vasculogenic impact of nintedanib was visible at the minimal concentrations of 10 nM, showing a significant increase in vessel permeability. Furthermore, nintedanib decreased microvessel density, diameter, and influenced fibroblast organization around endothelial microvessels. These results show that nintedanib acts on the endothelial network formation and endothelial-perivascular interactions. Advanced in vitro microvasculature models may thus serve to pinpoint the mechanistic effect of anti-fibrotic drugs on the microvascular remodeling in 3D and refine findings from animal studies.

McKenzie mechanical syndromes coincide with biopsychosocial influences, including central sensitization: a descriptive study of individuals with chronic neck pain.

BACKGROUND: Mechanical diagnosis and therapy (MDT) aims to assess and classify patients into theoretically mutually exclusive subgroups, in order to direct treatment. However, the latest evidence for biopsychosocial influence-central sensitization (CS) and psychological distress-have not been assessed in conjunction with MDT. OBJECTIVES: (1) Determine the percentage of patients categorized into the MDT subgroups; (2) characterize the biopsychosocial clinical profile (presence of CS and psychological distress); and (3) identify associations between pain, disability, and biopsychosocial influences among this cohort. METHODS: Eighty four patients with chronic neck pain were recruited by 10 certified MDT therapists using a convenience (consecutive) sampling method. Patients were evaluated using MDT principles and also completed an online survey to measure CS (using the Central Sensitization Inventory [CSI]), pain catastrophizing and kinesiophobia. RESULTS: The proportions of the subgroups derangement (DER), dysfunction, postural and 'other' were 74.4, 2.4, 1.2, 20.7%, respectively. CS was observed in 62% of our sample (CSI score ≥ 40). CS was also observed in 64.7% of patients of the DER subgroup. Almost half of our sample (47.8%) demonstrated the co-occurrence of CS and DER, while 38% presented with DER syndrome, CS, and kinesiophobia. CONCLUSION: The majority of our patients were classified as DER; they also presented with high levels of CS and/or psychological distress. This suggests that MDT mechanical subgroups, particularly DER, can present with co-occurring biopsychosocial influences. Without assessing CS and psychological distress, MDT therapists may miss crucial information. Further research is required to determine the optimal management of patients presenting with mechanical and non-mechanical drivers of pain.