Targeting CD44v6 for fluorescence-guided surgery in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is an often highly invasive tumor, infiltrating functionally important tissue areas. Achieving complete tumor resection and preserving functionally relevant tissue structures depends on precise identification of tumor-free resection margins during surgery. Fluorescence-guided surgery (FGS), by intraoperative detection of tumor cells using a fluorescent tracer, may guide surgical excision and identify tumor-positive resection margins. Using a literature survey on potential surface molecules followed by immunohistochemical validation, we identified CD44 variant 6 (CD44v6) as a constitutively expressed antigen in the invasion zone of HNSCC lesions. The monoclonal anti-CD44v6 antibody BIWA was labeled with both a near-infrared fluorescent dye (IRDye800CW) and a radioactive label (Indium-111) and dual-modality imaging was applied in a locally invasive tumor mouse model. BIWA accurately detected human HNSCC xenografts in mice with a tumor uptake of 54 ± 11% ID/g and invasion regions with an accuracy of 94%. When dissected under clinical-like conditions, tumor remnants approximately 0.7 mm in diameter consisting of a few thousand cells were identified by fluorescence imaging, resulting in reliable dissection of invasive microregions. These data indicate that CD44v6 is a suitable target for reliable near-infrared detection and FGS of invasive HNSCC lesions in vivo.</p

An integrative approach to ancient agricultural terraces and forms of dependency: the case of Cutamalla in the prehispanic Andes

This paper presents an integrative and interdisciplinary approach to the study of ancient agricultural terraces and food production systems. Our approach consists of (1) a resource dependency theoretical framework and (2) the application of a variety of archaeological and geoscientific methods, including archaeological and geomorphological surveys, archaeological excavations, drone surveys, mapping based on satellite imagery and high-resolution digital elevation models (DEMs), geographic information system (GIS) applications, soil testing, phytolith analysis, radiocarbon dating, and calculations of food supply capacity and labor requirements. We apply these to the prehispanic site of Cutamalla (3,300 m asl) in the southern Peruvian Andes, which serves as an ideal and pioneering case study. Previous research has focused primarily on the settlement of Cutamalla, particularly through large-scale archaeological excavations, but less attention has been paid to the extensive farming terraces surrounding the settlement and the close relationship between agricultural and settlement activities. By analyzing both the terrace and settlement levels, we take a new perspective and introduce the term agricultural terrace-settlement system for such complexes. Our results show that the residential occupation of Cutamalla and the use of the surrounding farming terraces coincided: the agricultural terrace-settlement system was intensively used for a relatively short period of about 200 years (~250–40 BCE) during the Formative Late Paracas and transitional Initial Nasca periods, long before the famous Inka terrace agricultural systems. There is no evidence of reoccupation of the site and subsequent reuse of the agricultural system. Our data also document the large extent of agricultural terraces around Cutamalla (221 ha) and that maize was likely a major crop grown there. Finally, we place these findings in their broader socio-economic and ecological context. Cutamalla was an important regional center and economic hub during a very dynamic period characterized by significant population growth and increased violence. Not only a more humid climate, but probably also forced collective labor were cornerstones of substantial agricultural production in Cutamalla and the region

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Daytime sleepiness in depression—underestimated in psychiatric inpatients

Background Sleep disorders are among the most common symptoms of depression. Both the ICD-10/11 and DSM‑5 list sleep disorders of all types as diagnostic criteria for depression, but these are not defined in detail. Objective This study focused on the prevalence of daytime sleepiness and associated sleep disorders in patients diagnosed with a severe depressive episode. Materials and methods In total, 192 inpatients with a moderate/severe depressive episode from an open acute psychiatric ward were included. Sleep history immediately after admission and sleep-related questionnaires, such as the Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and Regensburg Insomnia Scale (RIS), were collected. Polysomnographic assessment was performed in 82 patients with suspected sleep disorders. Patient groups (e.g., with and without sleepiness or apnea) were compared. Results The prevalence of daytime sleepiness (ESS > 10) was 25.3%. Fatigue and insomnia were reported in 66.7 and 75.7% of patients, respectively. Polysomnography revealed a prevalence of sleep apnea of 18.2%, and sleep apnea was newly diagnosed in 80% of these patients. Daytime sleepiness was more common in patients with undiagnosed sleep apnea. Patients with daytime sleepiness had more fatigue but did not have more severe depression. Conclusion The present results highlight the importance of assessing sleep history in psychiatric patients, especially those with depression. The ESS may be a useful tool to specifically assess daytime sleepiness as opposed to depression-related fatigue. A systematic assessment of sleepiness and specific sleep disorders, in particular sleep apnea, might contribute to improved treatment of inpatients with depression

Increase in CSF Abeta during the very early phase of cerebral Abeta deposition in mouse models

Abnormalities in the brain of Alzheimer’s Disease (AD) patients are thought to start long before the first clinical symptoms emerge. The identification of affected individuals at this “preclinical AD” stage relies on biomarkers such as decreased levels of the β-amyloid peptide (Aβ) in the cerebrospinal fluid (CSF) and brain retention of amyloid-binding agents using positron emission tomography. However, these biomarkers are limited by the lack of longitudinal profiles and lack pathological conformation in brain. To this end we have studied CSF Aβ changes in three genetically-defined amyloid precursor protein (APP) transgenic mouse models focusing our analysis on the time of the initial Aβ deposition in brain, which differs significantly between the models studied. Remarkably, while we confirmed the CSF Aβ decrease during the course of brain amyloid deposition, a temporary 20-30% increase in CSF Aβ40 and 42 was found at the time of the appearance of the first individual Aβ plaques in all the three models. These results together with emerging indications of similar CSF Aβ increases at very early stages in familial and sporadic AD suggest that increased CSF Aβ levels may constitute the first detectable biomarker change in the AD pathological process. This important observation opens new perspectives in patient selection and stratification for preventive treatment strategies and is an incentive to the discovery of additional “preclinical AD” biomarkers

Relative importance of speech and voice features in the classification of schizophrenia and depression

Abstract Speech is a promising biomarker for schizophrenia spectrum disorder (SSD) and major depressive disorder (MDD). This proof of principle study investigates previously studied speech acoustics in combination with a novel application of voice pathology features as objective and reproducible classifiers for depression, schizophrenia, and healthy controls (HC). Speech and voice features for classification were calculated from recordings of picture descriptions from 240 speech samples (20 participants with SSD, 20 with MDD, and 20 HC each with 4 samples). Binary classification support vector machine (SVM) models classified the disorder groups and HC. For each feature, the permutation feature importance was calculated, and the top 25% most important features were used to compare differences between the disorder groups and HC including correlations between the important features and symptom severity scores. Multiple kernels for SVM were tested and the pairwise models with the best performing kernel (3-degree polynomial) were highly accurate for each classification: 0.947 for HC vs. SSD, 0.920 for HC vs. MDD, and 0.932 for SSD vs. MDD. The relatively most important features were measures of articulation coordination, number of pauses per minute, and speech variability. There were moderate correlations between important features and positive symptoms for SSD. The important features suggest that speech characteristics relating to psychomotor slowing, alogia, and flat affect differ between HC, SSD, and MDD