The acute inflammatory response to copper(II)-doped biphasic calcium phosphates.

Infection and inflammation are two key features to consider to avoid septic or aseptic loosening of bone-implanted biomaterials. In this context, various approaches to fine-tune the biomaterial's properties have been studied in order to modulate the crosstalk between immune and skeletal cells. Cation-doping strategies for tuning of calcium phosphates properties has been evidenced as a promising way to control the biomaterial-induced inflammatory process, and thus improving their osteoimmunomodulatory properties. Copper(II) ions are recognized for their antibacterial potential, but the literature on their impact on particulate material-induced acute inflammation is scarce. We synthesized copper(II) ions-doped biphasic calcium phosphate (BCP), intended to exhibit osteoimmunomodulatory properties. We addressed in vitro, for the first time, the inflammatory response of human primary polymorphonuclear neutrophils (PMNs) to copper(II) ions-doped or undoped (BCP) powders, synthesized by an original and robust wet method, in the presence or absence of LPS as a costimulant to mimic an infectious environment. ELISA and zymography allowed us to evidence, in vitro, a specific increase in IL-8 and GRO-α secretion but not MIP-1ß, TNF-α, or MMP-9, by PMNs. To assess in vivo relevance of these findings, we used a mouse air pouch model. Thanks to flow cytometry analysis, we highlighted an increased PMN recruitment with the copper(II) ions-doped samples compared to undoped samples. The immunomodulatory effect of copper(II) ions-doped BCP powders and the consequent induced moderate level of inflammation may promote bacterial clearance by PMNs in addition to the antimicrobial potential of the material. Copper(II) doping provides new insights into calcium phosphate (CaP)-based biomaterials for prosthesis coating or bone reconstruction by effectively modulating the inflammatory environment.

Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC).

BACKGROUND: The MHC class I chain-related protein A (MICA) and protein B (MICB) participate in tumor immunosurveillance and may be important in colorectal cancer, but have not been examined in colorectal cancer development. METHODS: sMICA and sMICB blood levels were measured by SomaScan in Visit 2 (1990-92, baseline) and Visit 3 (1993-95) samples in cancer-free participants in the Atherosclerosis Risk in Communities Study. We selected rs1051792, rs1063635, rs2516448, rs3763288, rs1131896, rs2596542, and rs2395029 that were located in or in the vicinity of MICA or MICB and were associated with cancer or autoimmune diseases in published studies. SNPs were genotyped by the Affymetrix Genome-Wide Human SNP Array. We applied linear and Cox proportional hazards regressions to examine the associations of preselected SNPs with sMICA and sMICB levels and colorectal cancer risk (236 colorectal cancers, 8,609 participants) and of sMICA and sMICB levels with colorectal cancer risk (312 colorectal cancers, 10,834 participants). In genetic analyses, estimates adjusted for ancestry markers were meta-analyzed. RESULTS: Rs1051792-A, rs1063635-A, rs2516448-C, rs3763288-A, rs2596542-T, and rs2395029-G were significantly associated with decreased sMICA levels. Rs2395029-G, in the vicinity of MICA and MICB, was also associated with increased sMICB levels. Rs2596542-T was significantly associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males (HR = 0.68; 95% confidence interval, 0.49-0.96) but not in females (Pinteraction = 0.08). CONCLUSIONS: Rs2596542-T associated with lower sMICA levels was associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males. IMPACT: These findings support an importance of immunosurveillance in colorectal cancer.

Facility- and ward-level factors associated with SARS-CoV-2 outbreaks among residents in long-term care facilities: A retrospective cohort study.

OBJECTIVES: Long-term care facilities (LTCFs) have been disproportionately impacted by COVID-19. Yet, the reasons why certain LTCFs are affected more by outbreaks are poorly understood. This study aimed to identify the facility- and ward-level factors associated with SARS-CoV-2 outbreaks among LTCF residents. METHODS: We conducted a retrospective cohort study of multiple Dutch LTCFs (N = 60; with 298 wards providing care for ∼5600 residents) from September 2020 to June 2021. A dataset was constructed linking SARS-CoV-2 cases among LTCF residents to facility- and ward-level factors. Multilevel logistic regression analyses examined the associations between these factors and the likelihood of a SARS-CoV-2 outbreak among residents. RESULTS: During periods of the Classic variant, the mechanical recirculation of air was associated with significantly increased odds of a SARS-CoV-2 outbreak. During periods of the Alpha variant, the factors associated with significantly increased odds included large ward size (≥21 beds), wards providing psychogeriatric care, fewer restrictions on staff movement between wards and facilities, and a greater number of cases among staff (>10 cases). CONCLUSION: Policy and protocols on reducing resident density, staff movement, and mechanical recirculation of air in buildings are recommended to enhance outbreak preparedness in LTCFs. The implementation of low-threshold preventive measures among psychogeriatric residents is important because they appear as a particularly vulnerable group.

Fecal ß-glucuronidase activity differs between hematopoietic cell and kidney transplantation and a possible mechanism for disparate dose requirements.

The intestinal microbiota produces ß-glucuronidase that plays an essential role in the metabolism of the immunosuppressant mycophenolate mofetil (MMF). This drug is commonly used in organ and hematopoietic cell transplantation (HCT), with variations in dosing across transplant types. We hypothesized that ß-glucuronidase activity differs between transplant types, which may account for differences in dosing requirements. We evaluated fecal ß-glucuronidase activity in patients receiving MMF post-allogeneic HCT and post-kidney transplant. Kidney transplant patients had significantly greater ß-glucuronidase activity (8.48 ± 6.21 nmol/hr/g) than HCT patients (3.50 ± 3.29 nmol/hr/g; P = .001). Microbially mediated ß-glucuronidase activity may be a critical determinant in the amount of mycophenolate entering the systemic circulation and an important factor to consider for precision dosing of MMF.

Surgical management in submucous cleft palate patients.

OBJECTIVES: The submucous cleft palate (SMCP) is considered to be the most subtle type of cleft palate. Early detection is important to allow on time intervention by speech therapy and/or surgical repair before the children already develop compensatory speech mechanisms. The purpose of this study was to investigate at what time children with a SMCP present, to determine when children are operated, and to analyze the postoperative outcomes for in SMCP children. PATIENT AND METHODS: Medical records from 766 individuals registered in the cleft registry in the Wilhelmina's Children's' Hospital, Utrecht, were retrospectively reviewed. Inclusion criteria were children diagnosed with SMCP. The following data were collected: age at diagnosis, physical examination, age at surgery, surgical technique, speech therapy pre- and post-surgery, otitis media, secondary cleft surgery, family history, syndromes, and other anomalies. RESULTS: In total, 56 SMCP children were identified. The mean age of diagnosis was 44.0 months (range 0-150, SD = 37.0). In 48 children (85.7%), surgical intervention was performed (Furlow plasty, intravelar veloplasty, pharyngoplasty, or Furlow combined with buccal flap). CONCLUSION: This retrospective study reconfirms that SMCP often presents late, even in a country with a modern healthcare system and adequate follow-up of all newborns by the so-called youth doctors in "children's healthcare centers" up to the age of 4 years old. Almost 86% of patients ultimately needed palate surgery when SMCP was suspected. CLINICAL RELEVANCE: Any child presenting with repeated episodes of otitis media, nasal regurgitation, or speech difficulties should have prompt consideration for SMCP as diagnosis.

High performance of a novel antigen detection test on nasopharyngeal specimens for diagnosing SARS-CoV-2 infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a major public health issue worldwide. Developing and evaluating rapid and easy-to-perform diagnostic tests is a high priority. The current study was designed to assess the diagnostic performance of an antigen-based rapid detection test (COVID-VIRO®) in a real-life setting. Two nasopharyngeal specimens of symptomatic or asymptomatic adult patients hospitalized in the Infectious Diseases Department or voluntarily accessing the COVID-19 Screening Department of the Regional Hospital of Orléans, France, were concurrently collected. The diagnostic specificity and sensitivity of COVID VIRO® results were compared to those of real-time reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) results. A subset of patients underwent an additional oropharyngeal and/or saliva swab for rapid testing. A total of 121 patients confirmed to be infected and 127 patients having no evidence of recent or ongoing infection were enrolled for a total of 248 nasopharyngeal swab specimens. Overall, the COVID-VIRO® sensitivity was 96.7% (CI, 93.5%-99.9%). In asymptomatic patients, symptomatic patients having symptoms for more than 4 days and those with an RT-qPCR cycle threshold value ≥ 32, the sensitivities were 100%, 95.8%, and 91.9%, respectively. The concordance between RT-qPCR and COVID VIRO® rapid test results was 100% for the 127 patients with no SARS-CoV-2 infection. The COVID-VIRO® test had 100% specificity and sensitivity greater than 95%, which are better than the recommendations set forth by the WHO (specificity ≥ 97%-100%, sensitivity ≥ 80%). These rapid tests may be particularly useful for large-scale screening in emergency departments, low-resource settings, and airports.

Nanobody-targeted photodynamic therapy for the treatment of feline oral carcinoma: a step towards translation to the veterinary clinic.

Nanobody-targeted photodynamic therapy (NB-PDT) has been developed as a potent and tumor-selective treatment, using nanobodies (NBs) to deliver a photosensitizer (PS) specifically to cancer cells. Upon local light application, reactive oxygen species are formed and consequent cell death occurs. NB-PDT has preclinically shown evident success and we next aim to treat cats with oral squamous cell carcinoma (OSCC), which has very limited therapeutic options and is regarded as a natural model of human head and neck SCC. Immunohistochemistry of feline OSCC tissue confirmed that the epidermal growth factor receptor (EGFR) is a relevant target with expression in cancer cells and not in the surrounding stroma. Three feline OSCC cell lines were employed together with a well-characterized human cancer cell line (HeLa), all with similar EGFR expression, and a low EGFR-expressing human cell line (MCF7), mirroring the EGFR expression level in the surrounding mucosal stroma. NBA was identified as a NB binding human and feline EGFR with comparable high affinity. This NB was developed into NiBh, a NB-PS conjugate with high PS payload able to effectively kill feline OSCC and HeLa cell lines, after illumination. Importantly, the specificity of NB-PDT was confirmed in co-cultures where only the feline OSCC cells were killed while surrounding MCF7 cells were unaffected. Altogether, NiBh can be used for NB-PDT to treat feline OSCC and further advance NB-PDT towards the human clinic.

Toward RGB LEDs based on rare earth-doped ZnO.

By using ZnO thin films doped with Ce, Tb or Eu, deposited via radiofrequency magnetron sputtering, we have developed monochromatic (blue, green and red, respectively) light emitting devices (LEDs). The rare earth ions introduced with doping rates lower than 2% exhibit narrow and intense emission peaks due to electronic transitions in relaxation processes induced after electrical excitation. This study proves zinc oxide to be a good host for these elements, its high conductivity and optical transparency in the visible range being as well exploited as top transparent electrode. After structural characterization of the different doped layers, a device structure with intense electroluminescence is presented, modeled, and electrically and optically characterized. The different emission spectra obtained are compared in a chromatic diagram, providing a reference for future works with similar devices. The results hereby presented demonstrate three operating monochromatic LEDs, as well as a combination of the three species into another one, with a simply-designed structure compatible with current Si technology and demonstrating an integrated red-green-blue emission.

Randomised clinical study: oral aspirin 325 mg daily vs placebo alters gut microbial composition and bacterial taxa associated with colorectal cancer risk.

BACKGROUND: Aspirin is associated with decreased risk of colorectal cancer (CRC), potentially by modulating the gut microbiome. AIMS: To evaluate the effect of aspirin on the gut microbiome in a double-blinded, randomised placebo-controlled pilot trial. METHODS: Healthy volunteers aged 50-75 received a standard dose of aspirin (325 mg, N = 30) or placebo (N = 20) once daily for 6 weeks and provided stool samples every 3 weeks for 12 weeks. Serial measurements of gut microbial community composition and bacterial abundance were derived from 16S rRNA sequences. Linear discriminant analysis of effect size (LEfSe) was tested for between-arm differences in bacterial abundance. Mixed-effect regression with binomial distribution estimated the effect of aspirin use on changes in the relative abundance of individual bacterial taxa via an interaction term (treatment × time). RESULTS: Over the study period, there were differences in microbial composition in the aspirin vs placebo arm. After treatment, four taxa were differentially abundant across arms: Prevotella, Veillonella, Clostridium XlVa and Clostridium XVIII clusters. Of pre-specified bacteria associated with CRC (n = 8) or aspirin intake (n = 4) in published studies, interactions were significant for four taxa, suggesting relative increases in Akkermansia, Prevotella and Ruminococcaceae and relative decreases in Parabacteroides, Bacteroides and Dorea in the aspirin vs placebo arm. CONCLUSION: Compared to placebo, aspirin intake influenced several microbial taxa (Ruminococcaceae, Clostridium XlVa, Parabacteroides and Dorea) in a direction consistent with a priori hypothesis based on their association with CRC. This suggests that aspirin may influence CRC development through an effect on the gut microbiome. The findings need replication in a larger trial.

A Simple Questionnaire as a First-Step Tool to Detect Specific Frailty Profiles: The Lorraine Frailty-Profiling Screening Scale.

OBJECTIVES: To propose a simple frailty screening tool able to identify frailty profiles. DESIGN: Cross-sectional observational study. SETTING: Participants were recruited in 3 different clinical settings: a primary care outpatient clinic (RURAL population, N=591), a geriatric day clinic (DAY-CLINIC population, N=76) and healthy volunteers (URBAN population, N=147). PARTICIPANTS: A total of 817 older adults (>70 years old) living at home were included. INTERVENTION: A 9-item questionnaire (Lorraine Frailty Profiling Screening Scale, LoFProSS), constructed by an experts' working group, was administered to participants by health professionals. MEASUREMENTS: A Multiple Correspondence Analysis (MCA) followed by a hierarchical clustering of the results of the MCA performed in each population was conducted to identify participant profiles based on their answers to LoFProSS. A response pattern algorithm was resultantly identified in the RURAL (main) population and subsequently applied to the URBAN and DAY-CLINIC populations and, in these populations, the two classification methods were compared. Finally, clinically-relevant profiles were generated and compared for their ability to similarly classify subjects. RESULTS: The response pattern differed between the 3 sub-populations for all 9 items, revealing significant intergroup differences (1.2±1.4 positive responses for URBAN vs. 2.1±1.3 for RURAL vs. 3.1±2.1 for DAY-CLINIC, all p<0.05). Five clusters were highlighted in the main RURAL population: "non-frail", "hospitalizations", "physical problems", "social isolation" and "behavioral", with similar clusters highlighted in the remaining two populations. Identification of the response pattern algorithm in the RURAL population yielded a second classification approach, with 83% of tested participants classified in the same cluster using the 2 different approaches. Three clinically-relevant profiles ("non-frail" profile, "physical frailty and diseases" profile and "cognitive-psychological frailty" profile) were subsequently generated from the 5 clusters. A similar double classification approach as above was applied to these 3 profiles revealing a very high percentage (95.6%) of similar profile classifications using both methods. CONCLUSION: The present results demonstrate the ability of LoFProSS to highlight 3 frailty-related profiles, in a consistent manner, among different older populations living at home. Such scale could represent an added value as a simple frailty screening tool for accelerated and better-targeted investigations and interventions.

Evaluation of patients' needs to design and assess a patient education program in cancer pain.

Purpose: Patient education constitutes a relevant strategy to improve pain management. In the field of therapeutic patient education (TPE), we aimed 1) to assess pain impact in cancer patients, 2) to identify patients' educative needs in pain management, and 3) to refine research criteria for its future evaluation. Patients and methods: Pain intensity, relief and interference were assessed in 75 cancer patients with unbalanced background pain. Self-assessment questionnaire evaluated i) patients' pain management and ii) their knowledge and needs in TPE. Results: Most patients experienced pain for more than 6 months and 41.6% reported adequate pain relief. Understanding pain and pain management were major patients' preferences (>58%). Most patients declared they knew their pain treatments, but fewer than half of them were able to name them. However, education concerning pain treatment was considered as essential in <30% of patients. Almost all patients (97.1%) stated pain education as beneficial, with a preference for individualized sessions (41.2%). In addition, the assessment criteria for its future evaluation were refined. Conclusion: Targeted population mainly concerned patients with persistent pain. Only half of patients reported pain relief despite antalgics. Patient education was declared as beneficial for almost all participants. Practice implications: Tailoring a pain TPE on patients' needs has the potential to help them to optimally manage their pain daily.

The use of throat packs in pediatric cleft lip/palate surgery: a retrospective study.

OBJECTIVES: Throat packs are commonly used to prevent ingestion or aspiration of blood and other debris during cleft lip/palate surgery. However, dislodgement or (partial) retainment after extubation could have serious consequences. The aim of the present study was to investigate the effect of omitting pharyngeal packing during cleft lip/palate surgery on the incidence of early postoperative complications in children. MATERIALS AND METHODS: A retrospective study was performed on all children who underwent cleft lip/palate surgery at the Wilhelmina Children's Hospital. This study compared the period January 2010 through December 2012 when pharyngeal packing was applied according to local protocol (group A) with the period January 2013 till December 2015 when pharyngeal packing was no longer applied after removal from the protocol (group B). Data were collected for sex, age at operation, cleft lip/palate type, type of repair, lateral incisions, length of hospital stay, and complications in the first 6 weeks after surgery. Early complications included wound dehiscence, postoperative bleeding, infection, fever, upper respiratory tract infection (URTI), and lower respiratory tract infection (LRTI). RESULTS: This study included 489 cleft lip/palate operations (group A n = 246, group B n = 243). A total of 39 (15.9%) early complications were recorded in group A and a total of 40 (16.5%) in group B. There were no significant differences (P = 0.902) in complications between the two groups; however, there was a significant difference (P < 0.001) in length of hospital stay between the two groups (group A 3.6 days vs group B 3.2 days). CONCLUSION: Omitting routine placement of throat packs in cleft lip/palate surgery was not associated with an increased early postoperative complication rate. Therefore, the traditional, routine placement of a throat pack during cleft lip/palate surgery can be questioned. CLINICAL RELEVANCE: The traditional, routine placement of a throat pack during cleft lip/palate surgery can be questioned.

Teen drivers' awareness of vehicle instrumentation in naturalistic research.

INTRODUCTION: Naturalistic driving methods require the installation of instruments and cameras in vehicles to record driving behavior. A critical, yet unexamined issue in naturalistic driving research is the extent to which the vehicle instruments and cameras used for naturalistic methods change human behavior. We sought to describe the degree to which teenage participants' self-reported awareness of vehicle instrumentation changes over time, and whether that awareness was associated with driving behaviors. METHOD: Forty-two newly-licensed teenage drivers participated in an 18-month naturalistic driving study. Data on driving behaviors including crash/near-crashes and elevated gravitational force (g-force) events rates were collected over the study period. At the end of the study, participants were asked to rate the extent to which they were aware of instruments in the vehicle at four time points. They were also asked to describe their own and their passengers' perceptions of the instrumentation in the vehicle during an in-depth interview. The number of critical event button presses was used as a secondary measure of camera awareness. The association between self-reported awareness of the instrumentation and objectively measured driving behaviors was tested using correlations and linear mixed models. RESULTS: Most participants' reported that their awareness of vehicle instrumentation declined across the duration of the 18-month study. Their awareness increased in response to their passengers' concerns about the cameras or if they were involved in a crash. The number of the critical event button presses was initially high and declined rapidly. There was no correlation between driver's awareness of instrumentation and their crash and near-crash rate or elevated g-force events rate. CONCLUSION: Awareness was not associated with crash and near-crash rates or elevated g-force event rates, consistent with having no effect on this measure of driving performance. PRACTICAL APPLICATIONS: Naturalistic driving studies are likely to yield valid measurements of driving behavior.

An appraisal of the impact of compositional and ripening parameters on CO2 diffusivity in semi-hard cheese.

This study focuses on CO2 diffusivity, which is one of the most important factors impacting eye growth in semi-hard cheese, but yet has scarcely been investigated in literature. The effect of compositional and ripening parameters on experimental CO2 diffusivity in semi-hard cheese was studied. CO2 diffusivity in semi-hard cheese showed a complex relationship with temperature in the range 4-25°C, represented by a quadratic curve with the highest diffusivity at 13°C. Salt was found to impact CO2 diffusivity, with a decrease of about 60% for 0-2.7% w/w salt addition, which may be ascribed to viscosity increase of the cheese matrix and "salting in" effect of protein. CO2 diffusivity was found to increase with moisture content from 39% to 42% w/w, then it decreased from 42% to 48% w/w. Inevitable changes in protein content of the three cheese variants may be responsible for the complex behaviour observed.

Impact of selected composition and ripening conditions on CO2 solubility in semi-hard cheese.

Despite CO2 being one of the most important gases affecting the quality of most semi-hard cheeses, the thermodynamic properties of this molecule in relation to cheese ripening have rarely been investigated. In this study the CO2 solubility coefficient was experimentally assessed in semi-hard cheese as a function of the most relevant compositional and ripening variables. As expected, CO2 solubility was found to linearly decrease with temperature in the range 2-25 °C. Unexpectedly, solubility was not significantly different at 39% and 48% moisture, while it was found lower at 42%. Unavoidable changes in protein content of the three cheese variants is suspected to produce an interaction with water content, leading to complex interpretation of the results. Increasing salt content in cheese from 0 to 2.7%w/w significantly decreased CO2 solubility by about 25%, probably due to the increased bonded water molecules in the cheese water phase.

Mechanistic model coupling gas exchange dynamics and Listeria monocytogenes growth in modified atmosphere packaging of non respiring food.

A mechanistic model coupling O2 and CO2 mass transfer (namely diffusion and solubilisation in the food itself and permeation through the packaging material) to microbial growth models was developed aiming at predicting the shelf life of modified atmosphere packaging (MAP) systems. It was experimentally validated on a non-respiring food by investigating concomitantly the O2/CO2 partial pressure in packaging headspace and the growth of Listeria monocytogenes (average microbial count) within the food sample. A sensitivity analysis has revealed that the reliability of the prediction by this "super-parametrized" model (no less than 47 parameters were required for running one simulation) was strongly dependent on the accuracy of the microbial input parameters. Once validated, this model was used to decipher the role of O2/CO2 mass transfer on microbial growth and as a MAP design tool: an example of MAP dimensioning was provided in this paper as a proof of concept.