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Nocturnal scratch is one major factor leading to impaired quality of life in atopic dermatitis (AD) patients. Therefore, objectively quantifying nocturnal scratch events aids in assessing the disease state, treatment effect, and AD patients’ quality of life. In this paper, we describe the use of actigraphy, highly predictive topological features, and a model-ensembling approach to develop an assessment of nocturnal scratch events by measuring scratch duration and intensity. Our assessment is tested in a clinical setting against the ground truth obtained from video recordings. The new approach addresses unmet challenges in existing studies, such as the lack of generalizability to real-world applications, the failure to capture finger scratches, and the limitations in the evaluation due to imbalanced data in the current literature. Furthermore, the performance evaluation shows agreement between derived digital endpoints and the video annotation ground truth, as well as patient-reported outcomes, which demonstrated the validity of the new assessment of nocturnal scratch.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headaches associated with segmental vasoconstriction of cerebral arteries, which may result in intracranial hemorrhage (ICH). There is a lack of contemporary data available regarding the ICH burden in RCVS cohort. Our aim of the study is to assess the ICH burden, associated risk factors, and discharge outcome of ICH in patients with RCVS.All patients diagnosed with RCVS in the 2016 Nationwide Readmission Database were identified using ICD-10 code after excluding patients with the concurrent diagnosis of primary angiitis. ICH was defined as both intraparenchymal (IPH), subarachnoid hemorrhage (SAH), and subdural hematoma (SDH). Categorical and continuous variables were assessed by the Rao-Scott Chi-square test and the Wilcoxon signed-rank sum test respectively. We used a multivariable survey-weighted logistic model to determine the association between ICH and RCVS patient-level characteristics.A total of 799 patients were identified with RCVS. Total hospitalization of ICH was 43.4% [(95% CI 36.4-50.4%); (n = 346)] including SAH 35.9% [(95% CI 29.7-42.1%); (n = 287)], IPH 13.1% [(95% CI 9.5-16.7%); (n = 105)] and SDH 3.6% [(95% CI 1.5-5.6%); (n = 28)]. Patients with hemorrhagic RCVS (H-RCVS) had a mean age (years ± SE) of 47.4 ± 1.1 vs. 45.5 ± 1.2 years in R-RCVS (p = 0.247); and were predominantly female (84.0% vs. 68.8%; p = 0.001); with longer inpatient stays (10.9 vs. 6.8 days; p = 0.016); and a higher inpatient cost ($44,300 vs. $21,350; p 0.001). On multivariable analyses, higher odds of ICH were female sex 2.57 (95% CI 1.45-4.55; p = 0.001), middle age-group (45-64 years) 1.87 (CI: 1.11-3.15; p = 0.018) and older age group ( 64 years) 3.72 (CI: 1.15-12.03; p = 0.029). About 67.0% of all H-RCVS patients were discharged home, with no observed inpatient mortality.Intracerebral hemorrhage is the most common vascular complication in hospitalized RCVS patients, resulting in longer hospitalizations with more invasive procedures and higher healthcare expenditure. However, overall outcomes are excellent regardless of types of ICH, with no inpatient mortality observed in patients with hemorrhagic RCVS. Female sex and middle to older age-group are associated with higher odds of ICH.

Diffusion tensor imaging (DTI) studies show widespread white matter abnormalities in schizophrenia, but it is difficult to directly relate these parameters to biological processes. Neurite orientation dispersion and density imaging (NODDI) is geared toward biophysical characterization of white matter microstructure, but only few studies have leveraged this technique to study white matter alterations. We recruited 42 schizophrenia patients (30 antipsychotic-naïve and 12 currently untreated) and 42 matched controls in this prospective study. We assessed the orientation dispersion index (ODI) and extracellular free water (FW) using single-shell DTI data before and after a 6-week trial of risperidone. Longitudinal data were available for 27 patients. Voxelwise analyses showed significantly increased ODI in the posterior limb of the internal capsule in unmedicated patients (242 voxels; x = −24; y = 6; z = 6; p

Clinicians have different techniques and varying levels of experience with the pivot shift test, introducing variability into its performance. The purpose of this study was to evaluate the influence of teaching and repetition on the success rate and anterior translation of the lateral knee compartment during the pivot shift test in a cadaveric ACL injury model. Twenty-five participants (five each of medical students, orthopaedic surgery residents, physical therapists, athletic trainers, sports medicine fellows) were recruited and a senior orthopaedic surgeon served as gold standard examiner. Each participant performed 20 pivot shift tests on lower extremity cadaveric specimens with ACL deficiency and lateral meniscectomy: 5 prior to education (baseline), 10 after watching an instructional video (passive teaching), and 5 after an interactive education session (active teaching). The anterior translation of the lateral knee compartment was recorded during each pivot shift test using electromagnetic tracking system. For medical students and orthopaedic surgery residents, significant improvement in success rate was found when compared to baseline (12% and 24%, respectively) after both passive (36% and 60%, respectively) and active teaching (52% and 72%, respectively) (p

We study patch solutions of a family of transport equations given by a parameter $$\alpha $$ , $$0< \alpha \alpha /2$$ are time integrable. This finite-time singularity criterion holds for lower regularity than the regularity shown in numerical simulations in Cordoba et al. (Proc Natl Acad Sci USA 102:5949–5952, 2005) and Scott and Dritschel (Phys Rev Lett 112:144505, 2014) for surface quasi-geostrophic patches, where the curvature of the contour blows up numerically. This is the first proof of a finite-time singularity criterion lower than or equal to the regularity in the numerics. Finally, we also improve results in Gancedo (Adv Math 217(6):2569–2598, 2008) and in Chae et al. (Commun Pure Appl Math 65(8):1037–1066, 2012), giving local existence for patches in $$H^{2}$$ for $$0

Purpose Disruption of the syndesmosis, the anterior-inferior tibiofibular ligament (AITFL), the posterior-inferior tibiofibular ligament (PITFL), and the interosseous membrane (IOM), leads to residual symptoms after an ankle injury. The objective of this study was to quantify tibiofibular joint motion with isolated AITFL- and complete syndesmotic injury and with syndesmotic screw vs. suture button repair compared to the intact ankle. Methods Nine fresh-frozen human cadaveric specimens (mean age 60 yrs.; range 38–73 yrs.) were tested using a six degree-of-freedom robotic testing system and three-dimensional tibiofibular motion was quantified using an optical tracking system. A 5 Nm inversion moment was applied to the ankle at 0°, 15°, and 30° plantarflexion, and 10° dorsiflexion. Outcome measures included fibular medial-lateral translation, anterior-posterior translation, and external rotation in each ankle state: 1) intact ankle, 2) AITFL transected (isolated AITFL injury), 3) AITFL, PITFL, and IOM transected (complete injury), 4) tricortical screw fixation, and 5) suture button repair. Results Both isolated AITFL and complete injury caused significant increases in fibular posterior translation at 15° and 30° plantarflexion compared to the intact ankle (p p Conclusion Ankle instability is similar after both isolated AITFL and complete syndesmosis injury and persists after suture button fixation in the sagittal plane in response an inversion stress. Sagittal instability with ankle inversion should be considered when treating patients with isolated AITFL syndesmosis injuries and after suture button fixation. Level of evidence Controlled laboratory study, Level V.

Previous investigations in gene expression changes in blood after radiation exposure have highlighted its potential to provide biomarkers of exposure. Here, FDXR transcriptional changes in blood were investigated in humans undergoing a range of external radiation exposure procedures covering several orders of magnitude (cardiac fluoroscopy, diagnostic computed tomography (CT)) and treatments (total body and local radiotherapy). Moreover, a method was developed to assess the dose to the blood using physical exposure parameters. FDXR expression was significantly up-regulated 24 hr after radiotherapy in most patients and continuously during the fractionated treatment. Significance was reached even after diagnostic CT 2 hours post-exposure. We further showed that no significant differences in expression were found between ex vivo and in vivo samples from the same patients. Moreover, potential confounding factors such as gender, infection status and anti-oxidants only affect moderately FDXR transcription. Finally, we provided a first in vivo dose-response showing dose-dependency even for very low doses or partial body exposure showing good correlation between physically and biologically assessed doses. In conclusion, we report the remarkable responsiveness of FDXR to ionising radiation at the transcriptional level which, when measured in the right time window, provides accurate in vivo dose estimates.

This study is one in series determining the potential of RAGE axis (receptor for advanced glycation end products, isoforms, ligands) as a biomarker in multiple sclerosis (MS). We evaluated serum levels of RAGE ligand, the high-mobility group box (HMGB)1 in MS patients, and assessed the correlation between HMGB1 serum levels and the use of disease-modifying drugs (DMDs), and between HMGB1 serum levels and indicators of MS disease severity. HMGB1 serum levels were compared between 96 (23 males) MS patients and 34 age- and gender-matched healthy controls (HCs) using enzyme-linked immunosorbent assays. DMD-naive MS patients had significantly higher HMGB1 serum levels compared with DMD-treated (P = 0.04) and compared with HCs (P = 0.01). HMGB1 serum levels were not significantly different between total MS patients (DMD-naive plus DMD-treated) and HCs (P = 0.09). DMD-naive MS patients in clinical relapse tended to have lower HMGB1 serum levels than clinically stable RRMS patients (P = 0.07). HMGB1 serum levels showed 0.65 area under the curve (95 % CI 0.55–0.95) sensitivity/specificity for MS clinical relapse. The role of HMGB1 in MS disease pathology and DMD modulation of this protein warrant further investigations.

Background Exposure to second-hand tobacco smoke (SHS) is one of the prime risk factors for chronic lung disease development. Smoking during pregnancy may lead to birth defects in the newborn that include pulmonary dysfunction, increased susceptibility to opportunistic pathogens, or initiation of childhood respiratory manifestations such as bronchopulmonary dysplasia (BPD). Moreover, exposure to SHS in early childhood can have negative impact on lung health, although the exact mechanisms are unclear. Autophagy is a crucial proteostatic mechanism modulated by cigarette smoke (CS) in adult lungs. Here, we sought to investigate whether SHS exposure impairs autophagy in pediatric lungs. Methods Pregnant C57BL/6 mice were exposed to room air or SHS for 14 days. The newborn pups were subsequently exposed to room air or SHS (5 h/day) for 1 or 14 days, and lungs were harvested. Soluble and insoluble protein fractions isolated from pediatric mice lungs were subjected to immunoblotting for ubiquitin (Ub), p62, VCP, HIF-1α, and β-actin. Results Our data shows that short-term exposure to SHS (1 or 14 days) leads to proteostasis and autophagy-impairment as evident by significant increase in accumulation of ubiquitinated proteins (Ub), p62 (impaired-autophagy marker) and valosin-containing protein (VCP) in the insoluble protein fractions of pediatric mice lungs. Moreover, increased HIF-1α levels in SHS-exposed mice lungs points towards a novel mechanism for SHS-induced lung disease initiation in the pediatric population. Validating the in vivo studies, we demonstrate that treatment of human bronchial epithelial cells (Beas2b cells) with the proteasome inhibitor (MG-132) induces HIF-1α expression that is controlled by co-treatment with autophagy-inducing drug, cysteamine. Conclusions SHS-exposure induced proteostasis/autophagy impairment can mediate the initiation of chronic lung disease in pediatric subjects. Hence, our data warrants the evaluation of proteostasis/autophagy-inducing drugs, such as cysteamine, as a potential therapeutic intervention strategy for SHS-induced pediatric lung diseases.

BACKGROUND AND PURPOSE: Target volume definitions for radiotherapy in pancreatic ductal adenocarcinoma (PDAC) vary substantially. Some groups aim to treat the primary tumor only, whereas others include elective lymph nodes (eLNs). eLNs close to the primary tumor are often included unintentionally within the treatment volume, depending on the respective treatment philosophies. We aimed to measure the percentages of anatomical coverage of eLNs by comparing four different contouring guidelines. PATIENTS AND METHODS: Planning target volumes (PTVs) were contoured using planning computed tomography (CT) scans of 11 patients with PDAC based on the Oxford, RTOG (Radiation Therapy Oncology Group), Michigan, and SCALOP (Selective Chemoradiation in Advanced Localised Pancreatic Cancer trial) guidelines. Clinical target volumes (CTVs) included the peripancreatic, para-aortic, paracaval, celiac trunk, superior mesenteric, and portal vein lymph node areas. Volumetric comparisons of the coverage of all eLN regions were conducted to illustrate the differences between the four contouring strategies. RESULTS: The PTV sizes of the RTOG and Oxford guidelines were comparable. The SCALOP and Michigan PTV sizes were similar to each other and significantly smaller than the RTOG and Oxford PTVs. A large variability of eLN coverage was found for the various subregions according to the respective contouring strategies. CONCLUSION: This is the first study to directly compare the percentage of anatomical coverage of eLNs according to four PTVs in the same patient cohort. Potential practical consequences are discussed in detail.

IgG4-related disease is a recently recognized systemic disorder involving multiple organs throughout the body. The multi-organ involvement of this disease was previously thought to occur as isolated, unrelated autoimmune disorders. Although virtually any part of the body may be involved in IgG4-related disease, abdominal manifestations tend to predominate in most affected individuals. While autoimmune pancreatitis is the most commonly encountered abdominal disorder in the setting of IgG4-related disease, the liver, kidneys, gastrointestinal tract, retroperitoneum, and mesentery may likewise be involved. Various diagnostic criteria for IgG4-related disease have been proposed based on physical exam, serology, and histopathologic confirmation. However, imaging plays an essential role in the diagnosis of this disorder, not only to establish the presence of IgG4-related disease, but to assess the severity and extent of systemic disease involvement.

Immunoincompetence after allogeneic hematopoietic stem cell transplantation (HSCT) affects in particular the T-cell lineage and is associated with an increased risk for infections, graft failure and malignant relapse. To generate large numbers of T-cell precursors for adoptive therapy, we cultured mouse hematopoietic stem cells (HSCs) in vitro on OP9 mouse stromal cells expressing the Notch-1 ligand Delta-like-1 (OP9-DL1). We infused these cells, together with T-cell-depleted mouse bone marrow or purified HSCs, into lethally irradiated allogeneic recipients and determined their effect on T-cell reconstitution after transplantation. Recipients of OP9-DL1-derived T-cell precursors showed increased thymic cellularity and substantially improved donor T-cell chimerism (versus recipients of bone marrow or HSCs only). OP9-DL1-derived T-cell precursors gave rise to host-tolerant CD4+ and CD8+ populations with normal T-cell antigen receptor repertoires, cytokine secretion and proliferative responses to antigen. Administration of OP9-DL1-derived T-cell precursors increased resistance to infection with Listeria monocytogenes and mediated significant graft-versus-tumor (GVT) activity but not graft-versus-host disease (GVHD). We conclude that the adoptive transfer of OP9-DL1-derived T-cell precursors markedly enhances T-cell reconstitution after transplantation, resulting in GVT activity without GVHD.

Influenza viral passaging through pre-vaccinated mice shows that emergent antigenic site mutations on the viral hemagglutinin (HA) impact host receptor-binding affinity and, therefore, the evolution of fitter influenza strains. To understand this phenomenon, we computed the Significant Interactions Network (SIN) for each residue and mapped the networks of antigenic site residues on a representative H1N1 HA. Specific antigenic site residues are ‘linked’ to receptor-binding site (RBS) residues via their SIN and mutations within “RBS-linked” antigenic residues can significantly influence receptor-binding affinity by impacting the SIN of key RBS residues. In contrast, other antigenic site residues do not have such “RBS-links” and do not impact receptor-binding affinity upon mutation. Thus, a potential mechanism emerges for how immunologic pressure on RBS-linked antigenic residues can contribute to evolution of fitter influenza strains by modulating the host receptor-binding affinity., National Institutes of Health (U.S.) (grant GM R37 GM057073-13), Singapore–MIT Alliance for Research and Technology, National Institutes of Health (U.S.) (grant AI058113)