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Goal: We previously demonstrated that near-infrared spectroscopy in vivo presents spectral features at 895 and 861 nm that accurately classify Alzheimer's disease, mild cognitive impairment, and age-matched control subjects. Our purpose here is to associate the 895 nm signal with $\beta$-amyloid. Methods: We applied our feature selection technique to subjects with and without leptomeningeal amyloid. We developed a novel concept, optical taxonomic signal, to determine the dependence of signal on source-detector distance. Results: Features at 891 and 768 nm discriminate between subjects with and without leptomeningeal $\beta$-amyloid. The variation of optical taxonomic signal with source-detector distance indicates that both signals come from the leptomeninges and not cerebral cortex. The two features are highly correlated and likely result from the same cellular material. Conclusions: The discovery of an 891 nm feature that clearly depends upon the presence of $\beta$-amyloid supports our hypothesis that the 895 nm feature previously discovered also reports $\beta$-amyloid.

Abstract Background As the primary cause of various preventable illnesses, smoking results in approximately five million premature deaths each year in the US and a multitude of adults living with serious illness. The majority of smokers know the health risks associated with smoking and intend to quit. However, quitting is very difficult partly because of insomnia and stress associated with it. Current tobacco cessation medications are not designed to address these problems, which may have contributed to their limited success in enabling cessation. Novel interventions are thus urgently needed to enhance success rates in tobacco cessation. Based on its historical usage and our preliminary data, kava is such a candidate. Kava, customarily enjoyed by South Pacific Islanders, is known for its relaxing effects, stress-relieving properties, and ability to enhance sleep. In the US, it is marketed and distributed as a dietary supplement due to its recognized calming properties. A pilot trial was performed among active smokers with a one-week ingestion of a kava supplement. The results for the first-time revealed kava’s potential in enabling tobacco cessation with effects on a panel of biological signatures. The primary goal of this trial is to replicate kava’s effects on the biological signatures of tobacco use, stress, and sleep in addition to its compliance and safety among those who smoke. Methods A double-blind randomized placebo controlled two-arm trial will enroll 76 smokers with intention to quit, who will consume AB-free kava at a dietary supplement dose or placebo, 3 times per day for 4 weeks with two follow-ups. Discussion The study will (1) monitor the adherence to and safety of AB-free kava consumption among smokers and evaluate changes in smoking habits, and (2) quantify a panel of non-invasive translatable biomarkers to objectively evaluate AB-free kava’s holistic effects on biological signatures associated with tobacco use, stress, and sleep. We hypothesize that AB-free kava is a novel and promising intervention to facilitate tobacco cessation via its holistic effects associated with managing stress and insomnia during abstinence. If the results from this study support our hypothesis, kava could emerge as an affordable and accessible dietary supplement candidate for tobacco cessation. Trial Registration registered on 04/14/2023 in ClinicalTrials.gov with the identifier NCT05814055.

Abstract Distinguishing periods of intermittent unrest from the run-up to eruption is a major challenge at volcanoes around the globe. Comparing multidisciplinary monitoring data with mineral chemistry that records the physical and spatio-temporal evolution of magmas fundamentally advances our ability to forecast eruptions. The recent eruption of Mauna Loa, Earth’s largest active volcano, provides a unique opportunity to differentiate unrest from run-up and improve forecasting of future eruptions. After decades of intermittent seismic and geodetic activity over 38 years of repose, Mauna Loa began erupting on 27 November 2022. Here we present a multidisciplinary synthesis that tracks the spatio-temporal evolution of precursory activity by integrating mineral and melt chemistry, fluid inclusion barometry, numerical modeling of mineral zoning, syn-eruptive gas plume measurements, the distribution and frequency of earthquake hypocenters, seismic velocity changes, and ground deformation. These diverse data indicate that the eruption occurred following a 2-month period of sustained magma intrusion from depths of 3–5 km up to 1–2 km beneath the summit caldera, providing a new model of the plumbing system at this very high threat volcano. Careful correlation of both the geochemistry and instrumental monitoring data improves our ability to distinguish unrest from the run-up to eruption by providing deeper understanding of the both the monitoring data and the magmatic system—an approach that could be applied at other volcanic systems worldwide.

Background: Explicit funding and industry affiliation are believed to potentially impact medical research. There have been an increasing number of studies that have evaluated this relationship. The purpose of this study is to determine whether industry affiliation influences the outcomes of randomized controlled trials that investigate the effectiveness of platelet-rich plasma (PRP) in the treatment of lateral epicondylitis. Methods: A search of PubMed, SPORTDiscus, and SCOPUS was performed using the search terms “lateral epicondylitis” and “platelet-rich plasma” as well as “tennis elbow” and “platelet-rich plasma.” Only studies from 2010 to present were considered. Final texts were then analyzed for industry affiliation and treatment efficacy. When determining whether a study was industry-affiliated, explicit financial supporters of the study, stated conflicts of interest, American Academy of Orthopaedic Surgeons disclosures, and the Centers for Medicare and Medicaid Services open payments database were assessed. Study outcomes were categorized as favorable, analogous, or unfavorable based on achieving a statistically significant (P

Innovative wood inspection technology is crucial in various industries, especially for determining wood quality by counting rings in each stave, a key factor in wine barrel production. (1) Background: Traditionally, human inspectors visually evaluate staves, compensating for natural variations and characteristics like dirt and saw-induced aberrations. These variations pose significant challenges for automatic inspection systems. Several techniques using classical image processing and deep learning have been developed to detect tree-ring boundaries, but they often struggle with woods exhibiting heterogeneity and texture irregularities. (2) Methods: This study proposes a hybrid approach combining classical computer vision techniques for preprocessing with deep learning algorithms for classification, designed for continuous automated processing. To enhance performance and accuracy, we employ a data augmentation strategy using cropping techniques to address intra-class variability in individual staves. (3) Results: Our approach significantly improves accuracy and reliability in classifying wood with irregular textures and heterogeneity. The use of explainable AI and model calibration offers a deeper understanding of the model’s decision-making process, ensuring robustness and transparency, and setting confidence thresholds for outputs. (4) Conclusions: The proposed system enhances the performance of automatic wood inspection technologies, providing a robust solution for industries requiring precise wood quality assessment, particularly in wine barrel production.

Abstract Background Patient involvement is most common during the first phases of a research project. Despite good intentions, maintaining meaningful collaborations throughout the research process doesn't seem easy. Several training programmes for researchers and patients have been developed to stimulate continuous involvement. These are mostly one-time training sessions at the start of a project, for researchers and patients separately. We aimed to co-create a prolonged side-by-side programme for pairs of patient representatives and researchers, to stimulate mutual learning from the start and throughout the research projects. Methods We developed a group training and peer-to-peer support programme lasting 2–3 years for 4–5 pairs of researchers and patient representatives working together on a research project. The programme took 30 h, spread over 6–8 meetings. The main goal was mutual and bi-directional learning and maintaining the collaboration throughout the research projects. From the start, the pairs were instructed to discuss communication, roles, expectations and responsibilities to prevent misunderstandings. The character of the meetings was intended to evolve from training and peer support into peer-group coaching and support for the whole group. The programme was not a fixed method, it was adjusted to the context and the needs of the participants. Results Thus far, the programme has been applied in 5 groups, with varying health topics and types of research. Patients’ prior knowledge of research methods and researchers' experience with patient involvement varied within the groups. As a result of the side-by-side training power imbalances within pairs were reduced. All participants gained knowledge and experience in patient involvement. In subsequent group coaching sessions, they discussed issues and dilemmas on an equal footing. Most pairs found their way of working together, adapted to the wishes and capabilities of both partners. Differences between pairs were found to improve the discussions. Conclusions We co-created a prolonged side-by-side programme for pairs of patient representatives and researchers, to stimulate mutual learning from the start and throughout the research projects. The programme proved feasible for groups with different research types and health conditions. It fulfils an unmet need for researchers, patients and funders.

Purpose: Our objective was to determine if patients with a distal radius fracture and concomitant lower-extremity fracture benefit from bridge plating when compared with volar plating. Methods: We conducted a retrospective cohort study evaluating distal radius fractures fixated by bridge or volar plating in orthopedic trauma patients with a concomitant lower-extremity fracture. Patients were prescribed a platform walker and followed for gait aid use and both upper and lower-extremity fracture-related outcomes. Results: Differences in platform walker use, radiographic findings, and rates of complications for both distal radius and lower-extremity fractures were comparable between groups. Conclusions: Although more studies are needed, it appears that this cohort of patient’s ability to mobilize using a gait aid is similar, regardless of the distal radius fracture fixation method. A concomitant lower-extremity fracture should not necessarily indicate bridge plating over volar plate fixation. Type of study/level of Evidence: Therapeutic Study IV.

Abstract Background Cardiac positron emission tomography (PET) offers non-invasive assessment of perfusion and left ventricular (LV) function from a single dynamic scan. However, no prior assessment of mitral regurgitation severity by PET has been presented. Application of indicator dilution techniques and gated image analyses to PET data enables calculation of forward stroke volume and total LV stroke volume. We aimed to evaluate a combination of these methods for measurement of regurgitant volume (RegVol) and fraction (RegF) using dynamic 15O-water and 11C-acetate PET in comparison to cardiovascular magnetic resonance (CMR). Results Twenty-one patients with severe primary mitral valve regurgitation underwent same-day dynamic PET examinations (15O-water and 11C-acetate) and CMR. PET data were reconstructed into dynamic series with short time frames during the first pass, gated 15O-water blood pool images, and gated 11C-acetate myocardial uptake images. PET-based RegVol and RegF correlated strongly with CMR (RegVol: 15O-water r = 0.94, 11C-acetate r = 0.91 and RegF: 15O-water r = 0.88, 11C-acetate r = 0.84, p 30mL) was 95% for 15O-water and 92% for 11C-acetate. Conclusions LV regurgitation severity quantified using cardiac PET correlated with CMR and showed high accuracy for discriminating patients from healthy volunteers.

Catching, carrying, and loading of broilers before transport to the slaughterhouse causes stress. In this study three catching methods (two manual (inverted, upright) and one mechanical) were compared using a cost-benefit analysis of animal welfare, ergonomics and economic analysis. Depopulation of approximately 5,000 broilers per catching method per flock (upright vs. inverted vs. mechanical: n=3; upright vs. inverted: n=9; inverted vs. mechanical: n=3 flocks) was analyzed on 15 commercial farms. Economic considerations (person-hours per 1,000 chickens), ergonomics (catcher survey, ergonomic assessment of simulated catching), and animal welfare on-farm (wing flapping frequency, catcher-bird interaction) and at the slaughterhouse (catch damage and DOA prevalence) were considered. Wing flapping frequency was lower (2.0 ± 0.1 vs. 5.4 ± 0.1, P < 0.001), and catcher-bird interaction was better (3.7 ± 0.2 vs. 4.4 ± 0.2, P < 0.01) for upright catching compared to inverted catching based on a 7-point Likert scale. Prevalence of catch damage was lower for upright versus mechanical catching (15.5 ± 1.3% vs. 17.7 ± 1.4%, P = 0.046). More person-hours per 1,000 broilers were required for upright versus inverted (1.6 ± 0.1 h vs. 1.0 ± 0.1 h) and mechanical catching (0.6 ± 0.3 h) (P < 0.001). Upright catching was 1.5 and 1.2 times more expensive than inverted and mechanical catching based on 20,000 broilers. Compared to inverted catching, fair compensation would increase by €0.012 (upright) and €0.006 (mechanical) per kg of live weight. An ergonomics expert rated manual catching as very demanding, but catchers (n = 16) disliked upright catching (more labor-intensive). This study revealed animal welfare benefits of upright versus inverted (less wing flapping, better catcher-bird interaction) and mechanical catching (less catch damage), whereas mechanical catching provided the best labor conditions. Widespread application of upright catching would require testing of entire flocks and collaboration with the poultry sector to determine fair compensation, improve labor conditions and identify strategies to minimize catch and load duration.

Background and purpose: Motion management strategies such as gating under breath-hold can reduce breathing-induced motion during stereotactic arrhythmia radioablation (STAR) for refractory ventricular tachycardia. However, heartbeat-induced motion is essential to define an appropriate cardiac internal target volume (ITV) margin. In this study, we introduce a patient- and segment-specific cardiac motion estimation method and cardiac motion data of the clinical target volume (CTV), ICD lead tips and left ventricle (LV) segments. Materials and methods: Data from 10 STAR-treated patients were retrospectively analyzed. The LV was semi-automatically segmented according to the 17-segment model. Electrocardiogram-gated contrast-enhanced breath-hold cardiac CTs were automatically non-rigidly registered for motion estimation. The correlation and significant differences between ICD tip motion and CTV motion were assessed using the Pearson correlation coefficient (PCC) and Wilcoxon signed-rank test, while spatial discrepancies with both CTV and segment motion were quantified using the Euclidean distance. Results: The CTVs (center of mass) moved 3.4 ± 1.4 mm and the ICD lead tips moved 4.9 ± 2.2 mm. The maximum motion per patient was observed in basal and mid-cavity LV segments in 3D. The PCC showed a strong positive motion correlation between the ICD tip and CTV in 3D (0.84), while the p-values indicated statistically significant differences in the right-left, anterior-posterior and 3D directions. Conclusion: The proposed methods enable patient- and segment-specific cardiac ITV margin estimation. The motion in most LV segments was limited, however, cardiac ITV margins may need adjustment in individual cases. The impact of cardiac motion on the dosimetry needs further investigation.

Purpose: To investigate the characteristics and rate of sociodemographic variables reported in randomized controlled trials (RCTs) studying platelet-rich plasma (PRP) injections in the treatment of knee osteoarthritis (OA). Methods: In January 2024, PubMed, Scopus, and Web of Science databases were queried for the phrase “Platelet-Rich Plasma Knee Osteoarthritis.” Included studies were RCTs investigating PRP use in knee OA published in English between 2012 and 2023. Each RCT was inspected for patient age and sex or gender as well as the following sociodemographic variables: race, ethnicity, insurance status, income, housing status, work status, and education. Data were presented in a descriptive fashion and analyzed using χ2 test and Fisher’s exact test to compare 2 and 3 categorical variables, respectively, with significance defined as P < .05. Results: From 2012 through 2023, 71 RCTs met inclusion criteria. Included publications reported both age and sex or gender in 71/71 papers (100%). Reporting rates for other sociodemographic variables were as follows: race (3/71, 4.23%), work status (5/71, 7.04%), and education (3/71, 4.23%). No studies included the ethnicity, insurance status, income, or housing status of the enrolled patients. There was no difference in reporting sociodemographic variables by journal (P = .083) or by year of publication (P = .340). Sociodemographic variables were reported significantly less frequently than age and sex or gender (P < .001). Conclusions: In this study, we found that age and sex or gender are always reported in RCTs of PRP use for knee OA. However, other sociodemographic variables, such as race, work status, and education, that may be important to understand are rarely reported. Clinical Relevance: Sociodemographic variables may affect outcomes in knee osteoarthritis. It is important to understand which of these variables are most studied and which variables are most overlooked. This will help us better understand the quality of the available information.

We have reported the case of a 36-year-old man with severe scrotal swelling that had remained undiagnosed after multiple diagnostic tests. The patient had presented with scrotal swelling, multiple weeping ulcers on the dorsal aspect of the scrotum, and worsening pain affecting his day-to-day functioning. Duplex ultrasound showed low- to no-flow hypervascularity and dependent edema suspicious for a vascular malformation. Treatment included sequential Gelfoam (Pfizer, New York, NY) embolization using ultrasound-guided direct cannulation and traditional angiography. The scrotal circumference decreased by 65%, with moderate relief of his pain. The details from the present case have highlighted the significance of vascular malformations, various diagnostic and therapeutic techniques used, and value of endovascular embolization.

Abstract. Objectives:. Does degree of comminution affect femoral version after intramedullary nailing of femoral shaft fractures? Design:. Retrospective. Setting:. Standard of care, Level II Trauma Center, Hospital. Patients/Participants:. We reviewed electronic medical records of consecutive patients from 2000 to 2009 with diaphyseal femoral shaft fractures treated with intramedullary nailing and with available early postoperative computed tomography scanograms. Four hundred seventeen patients were identified, and 307 met inclusion criteria. Intervention:. Intramedullary nailing of the femur. Main Outcome Measurements:. Our primary study measure, determined before data collection, was the difference in femoral version between the uninjured limb and the injured limb. Femoral version was determined on postoperative computed tomography scanograms and reviewed by a fellowship trained musculoskeletal radiologist and a senior orthopaedic surgeon. Results:. Fractures were classified by an experienced orthopaedic trauma attending surgeon. OTA/AO type A fractures were the most common (51.5%), followed by type B (30.0%) and type C (18.5%). When categorized according to the Winquist system, 49.5% were type 1, 14.7% were type 2, 21.2% were type 3, and 14.7% were type 4. In univariate analysis, none of the classification systems were predictive of postoperative difference in femoral version (OTA/AO types and subtypes, OTA/AO types only, all Winquist types, and low-grade vs. high-grade Winquist; P > 0.05 for all). Subsequently, multivariate models did not yield any significant predictors. Conclusions:. Increasing degree of comminution based on fracture classifications had no significant impact on obtaining acceptable femoral version after intramedullary nailing. Level of Evidence:. Level III.

Flexible policies aimed at irrigated agriculture are essential to adapt to climate change. Despite the importance of this goal, little published work has conceptualized, formulated, developed, and applied an integrated optimization framework for irrigated agriculture to guide adaptation to climate-related water stress. This research addresses the question: how can water management plans for irrigated agriculture be designed to minimize economic losses caused by adapting to climate-induced water stress? The study answers this by developing an optimization approach that identifies water use patterns to minimize farm income losses during water shortages, considering three water shortage sharing programs. An optimization model, calibrated using positive mathematical programming, is applied to replicate historical land use while adapting to future water supplies that deviate from the historical pattern. The analysis focuses on two irrigated regions in North America’s Rio Grande Basin, illustrating land use, water use, and cropping patterns that minimize regional farm economic losses to shortages. These losses are assessed under three water-sharing strategies: intercrop and interdistrict trading (IIT), intercrop and intradistrict trading (IRT), and no trading (NT). The results demonstrate that IIT yields an average economic gain of $2.824 million per year, while IRT results in an average gain of $2.600 million per year compared to NT. These findings offer valuable insights for water managers, scientists, stakeholders, and policymakers tasked with developing irrigation management strategies in arid regions facing future water supply challenges. The methods developed and results shown here highlight a path forward, using scientific, economic, and policy innovations to strengthen agricultural livelihoods in regions facing uncertain water availability.

Abstract Light sheet fluorescence microscopy (LSFM) is a transformative imaging method that enables the visualization of non-dissected specimen in real-time 3D. Optical clearing of tissues is essential for LSFM, typically employing toxic solvents. Here, we test the applicability of a non-hazardous alternative, ethyl cinnamate (ECi). We comprehensively characterized autofluorescence (AF) spectra in diverse murine tissues—ocular globe, knee, and liver—employing LSFM under various excitation wavelengths (405–785 nm) to test the feasibility of unstained samples for diagnostic purposes, in particular regarding percutaneous biopsies, as they constitute to most harvested type of tissue sample in clinical routine. Ocular globe structures were best discerned with 640 nm excitation. Knee tissue showed complex variation in AF spectra variation influenced by tissue depth and structure. Liver exhibited a unique AF pattern, likely linked to vasculature. Hepatic tissue samples were used to demonstrate the compatibility of our protocol for antibody staining. Furthermore, we employed machine learning to augment raw images and segment liver structures based on AF spectra. Radiologists rated representative samples transferred to the clinical assessment software. Learning-generated images scored highest in quality. Additionally, we investigated an actual murine biopsy. Our study pioneers the application of AF spectra for tissue characterization and diagnostic potential of optically cleared unstained percutaneous biopsies, contributing to the clinical translation of LSFM.

Irrigated agriculture throughout much of the western United States relies on water resources that are under increasing stress from more frequent and severe droughts, reduced snowpack, and changes in the timing of runoff. Much of the water used for irrigation in that region passes through lands managed by irrigation organizations. These organizations play an important role in the use, allocation, and conservation of water resources through the maintenance of conveyance infrastructure, administration of rights to use water, and distribution of water to users. However, little work has been published to date systematically describing economic effects from alternative irrigation water trading arrangements for adapting to drought and climate change. The contribution of this work is to fill a gap in previous research by assessing the economic performance of various water trading arrangements for adapting to water shortages. We secured U.S. Department of Agriculture data on irrigation water use patterns in the central part of the Rio Grande Basin of the American Southwest to support formulation of a mathematical model predicting water use patterns to assess impacts on farm income associated with a range of water shortages and water trading arrangements for adapting to these shortages. Model results show that unlimited water trading minimizes farm income lost from shortages, while a more limited geographic scope for trading also moderates farm income losses. Among the three shortage sharing methods considered, a proportional sharing of shortages with no trading produces the greatest loss in farm income for adapting to shortage. These findings suggest that water trading arrangements have an important role play in adapting to water supply changes. Our results provide science-informed guidance to water managers, stakeholders, and policymakers tasked with discovering efficient water shortage adaptation plans for arid and semi-arid irrigation regions internationally.

ABSTRACT: This study explores upright versus inverted catching and crating of spent laying hens. Both catching methods were compared using a cost-benefit analysis that focused on animal welfare, ergonomic, and financial considerations. Data were collected on seven commercial farms (one floor system and six aviary systems) during depopulation of approximately 3,000 hens per method per flock. Parameters such as wing flapping frequency, catcher bird interaction, incidence of catching damage and hens dead on arrival (DOA) were measured and compared between catching methods. Ergonomic evaluations were performed via catcher surveys and expert assessment of video recordings. The wing flapping frequency was lower (3.1 ± 0.6 vs. 4.0 ± 0.5, P < 0.001) and handling was gentler (1.9 ± 0.5 vs. 4.4 ± 0.5, P < 0.001), both on a 7-point Likert scale, for upright versus inverted catching. However, more person-hours per 1000 hens were required for upright than inverted catching (8.2 ± 3.2 h vs. 4.8 ± 2.0 h, P = 0.011), with only wing bruises being significantly less common for upright than inverted catching (1.1 ± 0.6 % vs. 1.7 ± 0.7%, P = 0.04). Upright catching was 1.8 times more expensive than inverted catching; compensation for this cost would require a premium price of approximately €0.0005 extra per egg. Ergonomically, both catching methods were considered demanding, although catchers (n = 29) preferred inverted catching. In conclusion, this study showed animal welfare benefits of upright vs. inverted catching. Industry adoption of upright catching will depend on compensation of the additional labor costs, adjustments to labor conditions and shorter loading times.

Abstract. Introduction:. Delay to surgery >24 hours has been shown to correlate with mortality rates in patients with hip fracture when left untreated. Many of these patients have multiple comorbidities, including aortic stenosis (AS), and undergo workup for operative clearance, which may delay time to surgery. The purpose of this study was to examine whether preoperative echocardiogram workup affects time to surgery, complications, and mortality after operative fixation for hip fracture. Methods:. Our institutional hip fracture registry was retrospectively reviewed for inclusion over a 3-year period. Patients who had a preoperative echocardiogram (yECHO) for operative clearance were compared with those who did not (nECHO). Demographic data, time to surgery, overall complication rate, and mortality at 30 days, 90 days, and 1 year were collected. Results:. Two cohorts consisted of 136 yECHO patients (45.8%) and 161 nECHO patients (54.2%). Thirty-two yECHO patients (23.5%) had AS. Patients in the yECHO cohort were more likely to have a complication for any cause compared with nECHO patients (25.7% vs. 10.6%, P = 0.01) and have a higher mortality rate at 1 year (38.9% vs. 17.4%, P = 0.001). There was no association found between AS and all-cause complication (P = 0.54) or 30-day (P = 0.13) or 90-day mortality rates (P = 0.79). However, patients with AS had a significantly higher mortality rate at 1 year (45.8% vs. 25.1%, P = 0.03). Conclusion:. This study reinforces the benefits of ensuring less than a 24-hour time to surgery in the setting of a hip fracture and identifies an area of preoperative management that can be further optimized to prevent unnecessary prolongation in time to surgery. Patients with known aortic stenosis are not associated with increased 30-day or 90-day mortality or all-cause complications. Surgical delays in the yECHO cohort were attributed to preoperative medical assessments, including echocardiograms and the management of comorbidities. Therefore, the selective utilization of preoperative echocardiograms is needed and should be reserved to ensure they have a definitive role in guiding the perioperative care of patients with hip fracture. Level of Evidence:. III.

Cold temperature (≤20 ᵒC) storage or handling is required to maintain the quality characteristics of chocolate after production throughout the supply chain. The objective of this study was to assess the retail conditions, challenges, and willingness of retailers to use cooling devices. A total of 228 chocolate retailers sampled from Kumasi and Accra were interviewed using questionnaires with both closed and open-ended questions. The purposive, snowballing, and random sampling techniques were used. The collected data were analyzed using SPSS version 26. The majority of the respondents were female (82 %), aged between 21 and 30 years (33.9 %) and had a maximum of Junior High School education (39.0 %). About 15.4 % were registered retailers of Cocoa Processing Company - Ghana, 56.1 % sold on the streets of which 71.1 % sold under no shade and 71.9 % sold all day. A proportion of 76.2 % reported having challenges in their chocolate retail business. Among these challenges softening dominated with about 78.1 % of the retailers reported experiencing it in their daily operations. Spoilage (18.9 %), damage during handling (35.1 %), oily surface (34.2 %), darker surface appearance (10.1 %), and whitish surface appearance (39.9 %) were other challenges faced by retailers. The majority (76.8 %) of the respondents affirmed elevated temperatures caused melting, oil leakage and fat bloom in chocolate leading to rejections by clients. A significant proportion (81.1 %) indicated a cooling device for retail is necessary and were willing to use it when made available. The findings show that vending conditions were generally unsuitable for the shelf-stability of chocolates. An innovative vending device with cooling system would serve as possible intervention to mitigate the challenges faced by chocolate retailers.

Background Many disease processes are influenced by circadian clocks and display ~24‐hour rhythms. Whether disruptions to these rhythms increase stroke risk is unclear. We evaluated the association between 24‐hour rest‐activity rhythms, stroke risk, and major poststroke adverse outcomes. Methods and Results We examined ~100 000 participants from the UK Biobank (aged 44–79 years; ~57% women) assessed with actigraphy (6–7 days) and 5‐year median follow‐up. We derived (1) most active 10‐hour activity counts across the 24‐hour cycle and the timing of its midpoint timing; (2) the least active 5‐hour count and its midpoint; (3) relative amplitude; (4) interdaily stability; and (5) intradaily variability, for stability and fragmentation of the rhythm. Cox proportional hazard models were constructed for time to (1) incident stroke (n=1652) and (2) poststroke adverse outcomes (dementia, depression, disability, or death). Suppressed relative amplitude (lowest quartile [quartile 1] versus the top quartile [quartile 4]) was associated with stroke risk (hazard ratio [HR], 1.61 [95% CI, 1.35–1.92]; P

Abstract Background There is a growing population of survivors of colorectal cancer (CRC). Fatigue and insomnia are common symptoms after CRC, negatively influencing health-related quality of life (HRQoL). Besides increasing physical activity and decreasing sedentary behavior, the timing and patterns of physical activity and rest over the 24-h day (i.e. diurnal rest-activity rhythms) could also play a role in alleviating these symptoms and improving HRQoL. We investigated longitudinal associations of the diurnal rest-activity rhythm (RAR) with fatigue, insomnia, and HRQoL in survivors of CRC. Methods In a prospective cohort study among survivors of stage I-III CRC, 5 repeated measurements were performed from 6 weeks up to 5 years post-treatment. Parameters of RAR, including mesor, amplitude, acrophase, circadian quotient, dichotomy index, and 24-h autocorrelation coefficient, were assessed by a custom MATLAB program using data from tri-axial accelerometers worn on the upper thigh for 7 consecutive days. Fatigue, insomnia, and HRQoL were measured by validated questionnaires. Confounder-adjusted linear mixed models were applied to analyze longitudinal associations of RAR with fatigue, insomnia, and HRQoL from 6 weeks until 5 years post-treatment. Additionally, intra-individual and inter-individual associations over time were separated. Results Data were available from 289 survivors of CRC. All RAR parameters except for 24-h autocorrelation increased from 6 weeks to 6 months post-treatment, after which they remained relatively stable. A higher mesor, amplitude, circadian quotient, dichotomy index, and 24-h autocorrelation were statistically significantly associated with less fatigue and better HRQoL over time. A higher amplitude and circadian quotient were associated with lower insomnia. Most of these associations appeared driven by both within-person changes over time and between-person differences in RAR parameters. No significant associations were observed for acrophase. Conclusions In the first five years after CRC treatment, adhering to a generally more active (mesor) and consistent (24-h autocorrelation) RAR, with a pronounced peak activity (amplitude) and a marked difference between daytime and nighttime activity (dichotomy index) was found to be associated with lower fatigue, lower insomnia, and a better HRQoL. Future intervention studies are needed to investigate if restoring RAR among survivors of CRC could help to alleviate symptoms of fatigue and insomnia while enhancing their HRQoL. Trial registration EnCoRe study NL6904 ( https://www.onderzoekmetmensen.nl/ ).

Background: Left bundle branch pacing (LBBP) is a novel physiological pacing technique which may serve as an alternative to cardiac resynchronization therapy (CRT) by biventricular pacing (BVP). This study assessed ventricular activation patterns and echocardiographic and clinical outcomes of LBBP and compared this to BVP. Methods: Fifty consecutive patients underwent LBBP or BVP for CRT. Ventricular activation mapping was obtained by ultra-high-frequency ECG (UHF-ECG). Functional and echocardiographic outcomes and hospitalization for heart failure and all-cause mortality after one year from implantation were evaluated. Results: LBBP resulted in greater resynchronization vs BVP (QRS width: 170 ± 16 ms to 128 ± 20 ms vs 174 ± 15 to 144 ± 17 ms, p = 0.002 (LBBP vs BVP); e-DYS 81 ± 17 ms to 0 ± 32 ms vs 77 ± 18 to 16 ± 29 ms, p = 0.016 (LBBP vs BVP)). Improvement in LVEF (from 28 ± 8 to 42 ± 10 percent vs 28 ± 9 to 36 ± 12 percent, LBBP vs BVP, p = 0.078) was similar. Improvement in NYHA function class (from 2.4 to 1.5 and from 2.3 to 1.5 (LBBP vs BVP)), hospitalization for heart failure and all-cause mortality were comparable in both groups. Conclusions: Ventricular dyssynchrony imaging is an appropriate way to gain a better insight into activation patterns of LBBP and BVP. LBBP resulted in greater resynchronization (e-DYS and QRS duration) with comparable improvement in LVEF, NYHA functional class, hospitalization for heart failure and all-cause mortality at one year of follow up.

Abstract The chemokine CXCL12 promotes glioblastoma (GBM) recurrence after radiotherapy (RT) by facilitating vasculogenesis. Here we report outcomes of the dose-escalation part of GLORIA (NCT04121455), a phase I/II trial combining RT and the CXCL12-neutralizing aptamer olaptesed pegol (NOX-A12; 200/400/600 mg per week) in patients with incompletely resected, newly-diagnosed GBM lacking MGMT methylation. The primary endpoint was safety, secondary endpoints included maximum tolerable dose (MTD), recommended phase II dose (RP2D), NOX-A12 plasma levels, topography of recurrence, tumor vascularization, neurologic assessment in neuro-oncology (NANO), quality of life (QOL), median progression-free survival (PFS), 6-months PFS and overall survival (OS). Treatment was safe with no dose-limiting toxicities or treatment-related deaths. The MTD has not been reached and, thus, 600 mg per week of NOX-A12 was established as RP2D for the ongoing expansion part of the trial. With increasing NOX-A12 dose levels, a corresponding increase of NOX-A12 plasma levels was observed. Of ten patients enrolled, nine showed radiographic responses, four reached partial remission. All but one patient (90%) showed at best response reduced perfusion values in terms of relative cerebral blood volume (rCBV). The median PFS was 174 (range 58-260) days, 6-month PFS was 40.0% and the median OS 389 (144-562) days. In a post-hoc exploratory analysis of tumor tissue, higher frequency of CXCL12+ endothelial and glioma cells was significantly associated with longer PFS under NOX-A12. Our data imply safety of NOX-A12 and its efficacy signal warrants further investigation.

This study combines theoretical modeling and experimental validation to explore anaerobic digestion comprehensively. Developing a computational model is crucial for accurately simulating a digester’s performance, considering various feedstocks and operational parameters. The main objective was to adapt the anaerobic digestion model 1 (ADM1) simulation code to align with the laboratory-scale anaerobic digestion reactor’s specifications, especially regarding the liquid–gas transfer process. Within this computational framework, users may define model parameters and elucidate processes occurring in compartments reflecting the physical design. The model accurately predicts total concentrations of chemical oxygen demand (COD) as well as the produced biogas, with an average difference of less than 10% between experimental and simulated data. This consistency underscores the reliability and effectiveness of the adapted model in capturing anaerobic digestion nuances under specified conditions.

Los herbicidas de síntesis son muy efectivos para controlar arvenses en diversas condiciones. Sin embargo, las aplicaciones indiscriminadas aumentan la contaminación ambiental, siendo necesario buscar alternativas más amigables con el entorno. El objetivo de la investigación fue evaluar la efectividad de extractos acuosos de plantas en el control preemergente de arvenses en caña de azúcar. En el Instituto de Investigaciones de la Caña de Azúcar de Villa Clara, se realizó un experimento semicontrolado con un esqueje de una yema del cultivar C86-12 por maceta y otro en parcelas de campo, con esquejes de tres yemas de los cultivares CP52-43 y C86-12. En ambos experimentos se asperjó Merlin Total CS 60 a 0,25 L ha-1 en un caldo de 200 L ha-1, así como extractos acuosos de hojas verdes de Pinus sp, Eucaliptus sp. y plantas completas de Cyperus rotundus L., aplicados a 800 L ha-1, 200 y 400 L ha-1 de caldo, respectivamente. El control de especies anuales de los extractos fue entre 62-72% y 49-55%. En el merlin total fue de 100 y 88% en ambos experimentos. El rendimiento agrícola en el segundo experimento solo tuvo diferencia significativa en el manejo de arvenses, donde los tratamientos superaron al control. Palabras clave: Bioherbicidas, Caña de Azúcar, Extractos Acuosos, Preemergencia, Rendimiento Agrícola.

Abstract Massive rotator cuff (RC) tendon tears are associated with progressive fibro-adipogenesis and muscle atrophy that altogether cause shoulder muscle wasting. Platelet derived growth factor β (PDGFRβ) lineage cells, that co-express PDGFRα have previously been shown to directly contribute to scar formation and fat accumulation in a mouse model of irreversible tendon and nerve transection (TTDN). Conversely, PDGFRβ+ lineage cells have also been shown to be myogenic in cultures and in other models of skeletal muscle injury. We therefore hypothesized that PDGFRβ demarcates two distinct RC residing subpopulations, fibro-adipogenic and myogenic, and aimed to elucidate the identity of the PDGFRβ myogenic precursors and evaluate their contribution, if any, to RC myo-regeneration. Lineage tracing revealed increasing contribution of PDGFRβ+ myo-progenitors to the formation of GFP+ myofibers, which were the most abundant myofiber type in regenerated muscle at 2 weeks post-TTDN. Muscle regeneration preceded muscle atrophy and both advanced from the lateral site of tendon transection to the farthest medial region. GFP+/PDGFRβ+Sca-1−lin−CXCR4+Integrin-β1+ marked a novel subset of satellite cells with confirmed myogenic properties. Further studies are warranted to identify the existence of PDGFRβ+ satellite cells in human and other mouse muscles and to define their myo-regenerative potential following acute and chronic muscle injury.

Abstract Background To effectively promote vaccine uptake, it is important to understand which people are most and least inclined to be vaccinated and why. In this study, we examined predictors of COVID-19 vaccine uptake and reasons for non-vaccination. Methods We conducted an online English-language survey study in December-2020, January-2021, and March-2021. A total of 930 US respondents completed all surveys. Multiple logistic regression models were run to test whether the early vaccine eligibility, demographic factors, and psychological factors predict getting at least one dose of a COVID-19 vaccination in January-2021 and in March-2021. Results The proportion of respondents who received ≥ 1-dose of a COVID-19 vaccine increased from 18% (January) to 67% (March). Older age predicted vaccine uptake in January (OR = 2.02[95%CI = 1.14–3.78], p

Infants born with intrauterine growth restriction (IUGR) have up to a five-fold higher risk of learning and memory impairment than those with normal growth. Using a mouse model of hypertensive diseases of pregnancy (HDP) to replicate uteroplacental insufficiency (UPI), we have previously shown that UPI causes premature embryonic hippocampal dentate gyrus (DG) neurogenesis in IUGR offspring. The DG is a brain region that receives the first cortical information for memory formation. In the current study, we examined the postnatal DG neuron morphology one month after delivery (P28) using recombinant adeno-associated viral labeling of neurons. We also examined DG microglia’s morphology using immunofluorescent histochemistry and defined the hippocampal cytokine/chemokine milieu using Luminex xMAP technology. We found that IUGR preserved the principal dendrite lengths but decreased the dendritic branching and volume of DG neurons. IUGR augmented DG microglial number and cell size. Lastly, IUGR altered the hippocampal cytokine/chemokine profile in a sex-specific manner. We conclude that the prematurely-generated neuronal progenitors develop abnormal morphologies postnatally in a cell-autonomous manner. Microglia appear to modulate neuronal morphology by interacting with dendrites amidst a complex cytokine/chemokine environment that could ultimately lead to adult learning and memory deficits in our mouse model.

TRANSVAC represents a long-running effort to accelerate the development of novel vaccines by integrating institutions from across Europe under a single collaborative framework. This initiative has empowered the global vaccine community since 2009 including contributing toward the development and optimization of vaccine candidates as well as the provision of new adjuvants, research protocols, and technologies. Scientific services were provided in support of 88 different vaccine development projects, and 400 professionals attended TRANSVAC training events on various vaccine-related topics. Here, we review the accomplishments of the TRANSVAC consortia and analyze the continued needs of academic and industrial vaccine developers in Europe. The findings highlight the benefits of coordination across different sectors, both through research infrastructures such as TRANSVAC and other mechanisms, to address the current and future global health challenges and ensure that European vaccine developers have the support required to successfully compete in the global market.

Inflammation models with the proinflammatory cytokine interleukin-1β (IL-1β) are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis (OA). The aim of this study was to systematically analyze the influence of IL-1β in a 3D chondral pellet culture model. Bovine articular chondrocytes were cultured to passage 3 and then placed in pellet culture. Titration of IL-1β (100–0.1 ng/mL) was performed with both human and bovine recombinant protein in chondrocyte culture for 2 weeks. Gene expression of anabolic (collagen 2, aggrecan, cartilage oligomeric protein (COMP), proteoglycan-4 (PRG-4)), catabolic matrix metallo proteinases (MMP-3, MMP-13), dedifferentiation (collagen 1) markers and inflammatory cytokines IL-6 and IL-8 was determined. Analysis of the cell culture medium was performed for the inflammatory markers IL-6 and nitric oxide (NO). In general, the influence of IL-1β was shown by a decrease in the expression of anabolic markers (collagen 2, aggrecan, PRG-4), whereas the catabolic markers MMP-3 and MMP-13 as well as the inflammatory markers IL-6 and IL-8 were significantly increased. This was observed both at the early time point (day 4) and at the late time point (day 14). The described inflammatory effects were confirmed by increased concentration-dependent release of NO and IL-6. The threshold concentration for a detectable effect compared to control differed between groups, but was reached earlier by homologous application of IL-1β. This study provides a systematic evaluation of IL-1β-specific effects on chondrocytes in a 3D pellet culture model, which is highly relevant for comparisons of studies in OA-specific drug development.

Improving the economic performance of range forage in drylands internationally faces challenges from economic, ecological, and climate stress. Stakeholders in these drylands wish to protect range forage ecosystems while assuring economic viability of ranching. Despite several recent research achievements, little work to date has integrated relationships among precipitation, grazing pressure, animal performance, and forage production to protect ranching incomes faced with economic, ecological, and climate stress in dryland areas. This work addresses that gap by developing an empirical mathematical programming model for optimizing economic performance of livestock grazing on range forage ecosystems that adapt to several stressors. Its unique contribution is to formulate and apply a ranch income optimization model calibrated using positive mathematical programming. The model replicates observed economic, forage, and climate conditions while accounting for interacting relations among stocking rates, forage conditions, grazing pressure, animal performance, and ranch economic productivity. Results show ranch incomes ranging from about $5 to $88 per acre and marginal values of forage ranging from $0.01 to $0.12 per pound of forage, depending on economic, ecological, and climate conditions. Results reveal how all these stressors affect economically optimized choices of grazing levels, ranch income, and economic values of forage for a range of six biomes seen in the US west. Results help livestock ranchers to adjust stocking and forage choices as well as farm policymakers who seek flexible government programs to adapt to changes in economic, ecological, and climate conditions. The work's importance comes from applicability to forage management problems in dry regions internationally.

Protein Tyrosine Phosphatase 1B (PTP1B) has emerged as a significant regulator of metabolic and cardiovascular disease. It is a non-transmembrane protein tyrosine phosphatase that negatively regulates multiple signaling pathways integral to the regulation of growth, survival, and differentiation of cells, including leptin and insulin signaling, which are critical for development of obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. Given PTP1B's central role in glucose homeostasis, energy balance, and vascular function, targeted inhibition of PTP1B represents a promising strategy for treating these diseases. However, challenges, such as off-target effects, necessitate a focus on tissue-specific approaches, to maximize therapeutic benefits while minimizing adverse outcomes. In this review, we discuss molecular mechanisms by which PTP1B influences metabolic and cardiovascular functions, summarize the latest research on tissue-specific roles of PTP1B, and discuss the potential for PTP1B inhibitors as future therapeutic agents.

Objective: Previous literature has described race and socioeconomic disparities in both treatment and outcomes following cervical spinal cord injuries (SCI). The goal of this study is to investigate the current state of parity in management and outcomes following SCI. Methods: We surveyed the National Inpatient Sample database (NIS) for patients admitted with primary diagnosis of cervical SCI. 49,320 patients were identified. Univariate and multivariate analyses were performed to evaluate racial and socioeconomic differences in SCI care and outcomes. Results: Compared to white patients, minority race was associated with a longer time from presentation to operative intervention (p

ABSTRACT: Environmental conditions during incubation and rearing can influence stress responsivity of laying hen pullets throughout their lifespan, and therefore have important implications for their welfare. In this study, a 12:12h green LED light-dark cycle during incubation and larvae provisioning as enrichment during rearing were tested as strategies to optimize early-life conditions and thereby decrease stress responsivity in ISA Brown laying hens. A combination of parameters was measured to indicate neuronal, physiological, and behavioral changes that may affect fear and stress. The proteins calbindin D28k (calbindin1), doublecortin (DCX), and neuronal nuclein protein (NeuN) were quantified after hatch as a proxy for brain plasticity. Plasma and feather corticosterone levels were measured after hatch and at the end of the rearing phase, and fearfulness was investigated through a series of behavioral tests (i.e., voluntary approach, open field, tonic immobility, and manual restraint tests). No effects of light during incubation were found on calbindin1, DCX, or NeuN. Neither of the treatments affected corticosterone levels in blood plasma and feathers. Light-incubated pullets showed less fearfulness towards humans in the voluntary approach test, but not in the other behavioral tests reported in this study. Larvae provisioning had no effect on behavior. Our study showed minor effects of light during incubation and no effects of enrichment during rearing on stress responsivity of laying hen pullets. The small effects may be explained by the enriched rearing conditions for all birds in this experiment (low stocking density, natural daylight, and 24/7 classical music). Given the promising results of lighted incubation in other studies, which were mostly performed in broiler chickens, and evidence regarding the positive effects of enrichment during rearing, the potential of these strategies to improve laying hen welfare needs to be explored further.

In most rabbit farms, breeding does kindle and nurse their kits in single-litter cages throughout their entire reproduction cycle. However, the protective behavior can lead to aggressive displays and injuries when the does are housed in groups. This study aimed to evaluate cage enrichment for reducing the agonistic behavior in part-time group-housed does. A total of eighty does with their 22-day-old kits were allocated to 20 multi-litter cages, with each cage housing four does and their litters for 10 days. Each multi-litter group was subjected to one of four treatments: alfalfa blocks as distraction material (A), wooden panels underneath the platforms (P), both alfalfa and wooden panels (AP), or no extra enrichment (controls, C). This experiment was replicated for three consecutive reproduction cycles. The skin injuries of the does and the kits were scored with a tagged visual analog scale before grouping and at one, three, six, eight, and 10 days after grouping. Computer vision techniques were used to continuously monitor rabbit activity and agonistic behavior (aggression and fleeing/chasing) during the first 24 h after grouping, specifically during light hours. During the first day in the group, 67.2% of the does and 13.4% of the kits acquired new injuries. This increased to 82.0 and 33.2%, respectively after 10 days in the group relative to the onset of grouping. The injury scores of the does increased toward the sixth day after grouping compared to the first (p

Background: Periprosthetic joint infection after total knee arthroplasty is commonly treated via 2-stage revision utilizing either articulating or static antibiotic cement spacers. While recent literature exhibits a slight functional advantage in favor of articulating spacers, those patients with a history of recurrent infection/multiple revision procedures are frequently excluded from these studies. The purpose of this study was to report infection eradication rates and efficacy of utilizing antibiotic-loaded locked intramedullary nail for infection for the multiply revised, infected total knee arthroplasty. Methods: A retrospective review was performed of all consecutive patients receiving static spacers between 2017 and 2020 at an academic medical center. Surgical techniques for all patients included irrigation and debridement using a reamer-irrigator-aspirator, injection of antibiotic-loaded calcium sulfate into the intramedullary canal, and nail placement. Antibiotic-loaded cement is then used to create a spacer block in the joint space. A Cox proportional hazard regression was run to identify risk factors for reinfection. Results: Forty-two knees in 39 patients were identified meeting inclusion criteria. Overall, there was an 68.8% infection eradication rate at an average of 46.9 months following spacer placement. The only risk factors identified on cox regression were increasing number of previous spacers, a surrogate for previous infections (hazards ratio = 14.818, P value = .021), and increasing operative time during spacer placement (hazards ratio = 1.014, P value = .039). Conclusions: Use of static spacers, in conjunction with reamer-irrigator-aspirator and antibiotic-loaded calcium sulfate, can be effective in treating chronic, complex periprosthetic joint infections in the setting of bone loss and or soft-tissue compromise and produced similar results to more simple infection scenarios.

During acetabular cup positioning, intraoperative measurements of cup anteversion were taken using both fluoroscopy and navigation system. With the C-arm introduced at 40°, an anteroposterior view of the pelvis is taken. The C-arm is then centered over the hip, showing an anteverted cup with an approximate inclination of 40°. The axial C-arm is tilted away until the cup opening is visualized as a straight line, indicating that the beam of the fluoroscopy is aligned with the cup’s anteversion. The tilt angle on the C-arm and anteversion reading on the navigation workstation were recorded. The high degree of agreement between fluoroscopic and navigation measurement of acetabular cup anteversion supports the use of fluoroscopy in settings with limited access to navigation systems in direct anterior total hip arthroplasty.

Abstract Background Temporomandibular disorders (TMD) are a collective term for pain and dysfunction of the masticatory muscles and the temporomandibular joints. The most common types of TMD are pain-related, which may impact the psychological behavior and quality of life. Currently, the most popular methods for the treatment of TMD patients are occlusal splint therapy, often in combination with physical- and/or pharmacotherapy. However, due to the complexity of etiology, the treatment of chronic TMD remains a challenge. Recently, CE-certified systems for non-invasive VNS (transcutaneous auricular vagus nerve stimulation, taVNS) have become available and show positive effects in the treatment of chronic pain conditions, like migraine or fibromyalgia, with which TMD shares similarities. Therefore, it is the main purpose of the study to evaluate the feasibility of daily taVNS against chronic TMD and to assess whether there is an improvement in pain severity, quality of life, and kinetic parameters. Methods This study is designed as a single-blinded, double-arm randomized controlled trial (RCT) in a 1:1 allocation ratio. Twenty adult patients with chronical TMD symptoms will be enrolled and randomized to stimulation or sham group. In the stimulation group, taVNS is performed on the left tragus (25 Hz, pulse width 250 µs, 28 s on/32 s off, 4 h/day). The sham group will receive no stimulation via a non-functional identical-looking electrode. Validated questionnaire data and clinical parameters will be collected at the beginning of the study and after 4 and 8 weeks. The compliance of a daily taVNS of patients with chronical TMD will be evaluated via a smartphone app recording daily stimulation time and average intensity. Additionally, the treatment impact on pain severity and quality of life will be assessed with different questionnaires, and the effect on the mandibular mobility and muscle activity will be analyzed. Discussion This is the first clinical trial to assess the feasibility of taVNS in patients with chronic TMD symptoms. If taVNS improves the symptoms of TMD, it will be a significant gain in quality of life for these chronic pain patients. The results of this pilot study will help to determine the feasibility of a large-scale RCT. Trial registration This study has been registered in the DRKS database (DRKS00029724).

Abstract Background Ionotropic glutamate receptors α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) modulate proliferation, invasion and radioresistance in glioblastoma (GB). Pharmacological targeting is difficult as many in vitro-effective agents are not suitable for in patient applications. We aimed to develop a method to test the well tolerated AMPAR- and NMDAR-antagonist xenon gas as a radiosensitizer in GB. Methods We designed a diffusion-based system to perform the colony formation assay (CFA), the radiobiological gold standard, under xenon exposure. Stable and reproducible gas atmosphere was validated with oxygen and carbon dioxide as tracer gases. After checking for AMPAR and NMDAR expression via immunofluorescence staining we performed the CFA with the glioblastoma cell lines U87 and U251 as well as the non-glioblastoma derived cell line HeLa. Xenon was applied after irradiation and additionally tested in combination with NMDAR antagonist memantine. Results The gas exposure system proved compatible with the CFA and resulted in a stable atmosphere of 50% xenon. Indications for the presence of glutamate receptor subunits were present in glioblastoma-derived and HeLa cells. Significantly reduced clonogenic survival by xenon was shown in U87 and U251 at irradiation doses of 4–8 Gy and 2, 6 and 8 Gy, respectively (p

Abstract Background Mounting evidence indicates potential associations between poor oral health status (OHS) and increased pneumonia risk. Relative pneumonia risk was assessed in the context of longitudinally documented OHS. Methods Electronic medical/dental patient data captured from 2007 through 2019 were retrieved from the integrated health records of Marshfield Clinic Health Systems. Participant eligibility initiated with an assessment of OHS, stratified into the best, moderate, or worst OHS groups, with the additional criterion of ‘no pneumonia diagnosis in the past 90 days’. Pneumonia incidence was longitudinally monitored for up to 1 year from each qualifying dental visit. Models were assessed, with and without adjustment for prior pneumonia incidence, adjusted for smoking and subjected to confounding mitigation attributable to known pneumonia risk factors by applying propensity score analysis. Time-to-event analysis and proportional hazard modeling were applied to investigate relative pneumonia risk over time among the OHS groups. Results Modeling identified associations between any incident pneumonia subtype and ‘number of missing teeth’ (p

Abstract Adults with sickle cell disease bear a mutation in the β-globin gene, leading to the expression of sickle hemoglobin (HbS; α2βS 2). Adults also possess the gene for γ-globin, which is a component of fetal hemoglobin (HbF, α2γ2); however, γ-chain expression normally ceases after birth. As HbF does not form the fibers that cause the disease, pharmacological and gene-modifying interventions have attempted to either reactivate expression of the γ chain or introduce a gene encoding a modified β chain having γ-like character. Here, we show that a single-site modification on the α chain, αPro114Arg, retards fiber formation as effectively as HbF. Because this addition to the repertoire of anti-sickling approaches acts independently of other modifications, it could be coupled with other therapies to significantly enhance their effectiveness.

Abstract Background Sepsis-induced immunosuppression is a frequent cause of opportunistic infections and death in critically ill patients. A better understanding of the underlying mechanisms is needed to develop targeted therapies. Circulating bile acids with immunosuppressive effects were recently identified in critically ill patients. These bile acids activate the monocyte G-protein coupled receptor TGR5, thereby inducing profound innate immune dysfunction. Whether these mechanisms contribute to immunosuppression and disease severity in sepsis is unknown. The aim of this study was to determine if immunosuppressive bile acids are present in endotoxemia and septic shock and, if so, which patients are particularly at risk. Methods To induce experimental endotoxemia in humans, ten healthy volunteers received 2 ng/kg E. coli lipopolysaccharide (LPS). Circulating bile acids were profiled before and after LPS administration. Furthermore, 48 patients with early (shock onset within 0.4 μg/kg/min) and 48 healthy age- and sex-matched controls were analyzed for circulating bile acids. To screen for immunosuppressive effects of circulating bile acids, the capability to induce TGR5 activation was computed for each individual bile acid profile by a recently published formula. Results Although experimental endotoxemia as well as septic shock led to significant increases in total bile acids compared to controls, this increase was mild in most cases. By contrast, there was a marked and significant increase in circulating bile acids in septic shock patients with severe liver failure compared to healthy controls (61.8 µmol/L vs. 2.8 µmol/L, p = 0.0016). Circulating bile acids in these patients were capable to induce immunosuppression, as indicated by a significant increase in TGR5 activation by circulating bile acids (20.4% in severe liver failure vs. 2.8% in healthy controls, p = 0.0139). Conclusions Circulating bile acids capable of inducing immunosuppression are present in septic shock patients with severe liver failure. Future studies should examine whether modulation of bile acid metabolism can improve the clinical course and outcome of sepsis in these patients. Graphical abstract

As part of the European Green Deal, the EU has recognised that there is a need to increase organic farming as well as improve animal welfare standards. The PIGLOW app was developed with these goals in mind and allows free-range and organic pig farmers to perform welfare assessments (WAs) of their pigs. The results of each WA contain automated feedback and benchmarking information. The objective of this two-year longitudinal study was to determine whether regular use of the app helps farmers improve pig welfare. Farmers (n = 12) were asked to perform 6 WAs for finisher pigs with the app. At the beginning and end of the study, a researcher visited each farm and performed a detailed WA to determine the welfare status of the pigs at both moments. Farmers (n = 11) also filled out surveys about their opinions on pig welfare and the PIGLOW app. The welfare results did not support that the use of the PIGLOW app had an overall effect on pig welfare, but suggested a positive effect on some specific welfare aspects. Farmers indicated that they found the app easy to use and found most of its elements very useful. However, when asked about the specific influence of the app on their opinions on pig welfare and the welfare of their pigs, they indicated that the app only had small effects. Responses suggested that the app could likely be more useful to new farmers who still have more to learn about animal welfare.

Background: Novel vaccines targeting the world’s deadliest pathogen Mycobacterium tuberculosis (Mtb) are urgently needed as the efficacy of the Bacillus Calmette–Guérin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule, and HLA-E-restricted Mtb-specific CD8+ T cells can control intracellular Mtb growth, making HLA-E a promising vaccine target for Mtb. Methods: In this study, we evaluated the frequency and phenotype of HLA-E-restricted Mtb-specific CD4+/CD8+ T cells in the circulation and bronchoalveolar lavage fluid of two independent non-human primate (NHP) studies and from humans receiving BCG either intradermally or mucosally. Results: BCG vaccination followed by Mtb challenge in NHPs did not affect the frequency of circulating and local HLA-E–Mtb CD4+ and CD8+ T cells, and we saw the same in humans receiving BCG. HLA-E–Mtb T cell frequencies were significantly increased after Mtb challenge in unvaccinated NHPs, which was correlated with higher TB pathology. Conclusions: Together, HLA-E–Mtb-restricted T cells are minimally induced by BCG in humans and rhesus macaques (RMs) but can be elicited after Mtb infection in unvaccinated RMs. These results give new insights into targeting HLA-E as a potential immune mechanism against TB.

Competent authorities of many countries, including Belgium, impose control measures (preventing wild bird access to feeders and water facilities, indoor confinement of captive birds, or fencing off outdoor ranges with nets) on professional and non-professional keepers of birds to prevent the spread of avian influenza (AI). Flemish laying hen farmers (FAR, n = 33) and private keepers of captive birds (PRI, n = 263) were surveyed about their opinion on and compliance with AI measures legally imposed during the most recent high-risk period before this survey in 2021. Participants answered questions on a 5-point Likert scale (1 = the worst, 3 = neutral, and 5 = the best). FAR indicated better compliance with the AI measures than PRI, except for net confinement. FAR indicated that they and other poultry farmers complied better with AI measures than PRI. Additionally, PRI indicated that they better complied than other PRI keepers. FAR regarded the AI measures as more effective than PRI. To prevent the spread of AI more effectively, national authorities could focus on information campaigns explaining to private bird keepers the need for the various control measures that they impose. If these campaigns fail, local authorities may need stricter enforcement or alternative ways to increase compliance.