The Emergence and Global Spread of Noninvasive Prenatal Testing.

Since its introduction in 2011, noninvasive prenatal testing (NIPT) has spread rapidly around the world. It carries numerous benefits but also raises challenges, often related to sociocultural, legal, and economic contexts. This article describes the implementation of NIPT in nine countries, each with its own unique characteristics: Australia, Canada, China and Hong Kong, India, Israel, Lebanon, the Netherlands, the United Kingdom, and the United States. Themes covered for each country include the structure of the healthcare system, how NIPT is offered, counseling needs and resources, and cultural and legal context regarding disability and pregnancytermination. Some common issues emerge, including cost as a barrier to equitable access, the complexity of decision-making about public funding, and a shortage of appropriate resources that promote informed choice. Conversely, sociocultural values that underlie the use of NIPT vary greatly among countries. The issues described will become even more challenging as NIPT evolves from a second-tier to a first-tier screening test with expanded use.

Delivery of Anticancer Drugs Using Microbubble-Assisted Ultrasound in a 3D Spheroid Model.

Tumor spheroids are promising three-dimensional (3D) in vitro tumor models for the evaluation of drug delivery methods. The design of noninvasive and targeted drug methods is required to improve the intratumoral bioavailability of chemotherapeutic drugs and reduce their adverse off-target effects. Among such methods, microbubble-assisted ultrasound (MB-assisted US) is an innovative modality for noninvasive targeted drug delivery. The aim of the present study is to evaluate the efficacy of this US modality for the delivery of bleomycin, doxorubicin, and irinotecan in colorectal cancer (CRC) spheroids. MB-assisted US permeabilized the CRC spheroids to propidium iodide, which was used as a drug model without affecting their growth and viability. Histological analysis and electron microscopy revealed that MB-assisted US affected only the peripheral layer of the CRC spheroids. The acoustically mediated bleomycin delivery induced a significant decrease in CRC spheroid growth in comparison to spheroids treated with bleomycin alone. However, this US modality did not improve the therapeutic efficacy of doxorubicin and irinotecan on CRC spheroids. In conclusion, this study demonstrates that tumor spheroids are a relevant approach to evaluate the efficacy of MB-assisted US for the delivery of chemotherapeutics.

Transcriptional regulation of CYR61 and CTGF by LM98: a synthetic YAP-TEAD inhibitor that targets in-vitro vasculogenic mimicry in glioblastoma cells.

Glioblastoma (GBM) is a highly angiogenic malignancy of the central nervous system that resists standard antiangiogenic therapy, in part because of an alternative process to angiogenesis termed vasculogenic mimicry. Intricately linked to GBM, dysregulation of the Hippo signaling pathway leads to overexpression of YAP/TEAD and several downstream effectors involved in therapy resistance. Little is known about whether vasculogenic mimicry and the Hippo pathway intersect in the GBM chemoresistance phenotype. This study seeks to investigate the expression patterns of Hippo pathway regulators within clinically annotated GBM samples, examining their involvement in vitro regarding vasculogenic mimicry. In addition, it aims to assess the potential for pharmacological targeting of this pathway. In-silico analysis of the Hippo signaling members YAP1, TEAD1, AXL, NF2, CTGF, and CYR61 transcript levels in low-grade GBM and GBM tumor tissues was done by Gene Expression Profiling Interactive Analysis. Gene expression was analyzed by real-time quantitative PCR from human U87, U118, U138, and U251 brain cancer cell lines and in clinically annotated brain tumor cDNA arrays. Transient gene silencing was performed with specific small interfering RNA. Vasculogenic mimicry was assessed using a Cultrex matrix, and three-dimensional capillary-like structures were analyzed with Wimasis. CYR61 and CTGF transcript levels were elevated in GBM tissues and were further induced when in-vitro vasculogenic mimicry was assessed. Silencing of CYR61 and CTGF, or treatment with a small-molecule TEAD inhibitor LM98 derived from flufenamic acid, inhibited vasculogenic mimicry. Silencing of SNAI1 and FOXC2 also altered vasculogenic mimicry and reduced CYR61/CTGF levels. Pharmacological targeting of the Hippo pathway inhibits in-vitro vasculogenic mimicry. Unraveling the connections between the Hippo pathway and vasculogenic mimicry may pave the way for innovative therapeutic strategies.

Selective synthesis of an elusive C-functional bis-cyclam and study of its inhibition of the CXCR4 chemokine receptor.

This article presents the controlled synthesis of a rare example of C,C'-linked bis-cyclam architecture in mild conditions through the "bis-aminal" route previously used for the advantageous synthesis of cyclam, N- and C-functional cyclams and N,N'-bis-cyclams. Two synthetic pathways were explored with the smart design of α,ß-unsaturated ketones or alkyl halides bis-cyclizing agents. The first led to the isolation of a key intermediate for the future design of N-functionalized bis-cyclams, whereas the second allowed the preparation of the targeted C,C'-xylylene-bis-cyclam under mild conditions with decent yield. This compound was then studied as a CXCR4 receptor inhibitor, one of the main applications known for bis-macrocyclic compounds, in particular in the context of HIV (human immunodeficiency virus) infection. Although results demonstrated that its potency is lower (i.e. 137-fold higher IC50) than the gold standard AMD3100 against HIV infection, clear evidence of CXCR4 inhibition is presented, confirming the potential of this novel architecture and related compounds in this research field.

Use of an Artificial Intelligence Device for Evaluating Blood Loss in Complex Major Orthopaedic Surgery Procedures.

BACKGROUND: An artificial intelligence algorithm that analyzes the pulse oximeter waveform in the fingertip can be used to determine the compensatory reserve index (CRI) in trauma patients. This measurement shows the remaining cardiovascular capacity and is known to be more specific and sensitive in detecting blood loss than are routine vital signs. We hypothesized that the CRI measurement could predict loss of reserve cardiovascular capacity in patients undergoing major orthopaedic surgery, and therefore could help in their management. METHODS: A total of 304 patients undergoing lower extremity arthroplasty consented to participate in waveform monitoring. Pulse oximeter waveforms were sensed with a fingertip probe and processed with a tablet computer that remained with the patient during surgery and recovery in the hospital. The CRI, systolic blood pressure, and heart rate were evaluated throughout the postoperative period. RESULTS: The CRI measurement identified a group of patients who were significantly more likely to require transfusions and emergency medical care (P = .000021). Patients who had morbid obesity were especially likely to have low CRI results and a high percentage of clinical events. A CRI of 0.40 or more was evaluated retrospectively as the criterion for withholding transfusion in 54 patients, but that group had a significantly higher incidence of transfusion later in treatment than did the cohort as a whole. The systolic blood pressure and heart rate were not useful in predicting the need for transfusion until late in treatment. CONCLUSIONS: This study suggests that the CRI measurement can identify patients at risk for transfusion and the need for urgent medical care and may aid in the management of blood loss and transfusion in major orthopedic surgery.

Fetal maceration and partial retention of fetal bones in 2 mares.

Pregnancy loss after Day 40 in mares usually results in the expulsion (abortion) of the fetus and placental membranes. However, fetal retention within the uterus is also a possible outcome, leading to either fetal mummification or maceration. Fetal maceration is septic decomposition of fetal tissues within the uterus following failure of expulsion. It requires the presence of bacteria and oxygen within the uterus, likely originating from an open cervix, and results in tissue autolysis, leaving only fetal bones remaining in the mare. Fetal maceration is a rare complication of pregnancy in mares that is usually associated with a recent history of abortion, a persistent vaginal discharge, and retention of numerous fetal bones. Here, we report 2 cases of fetal maceration with retention of only a few fetal bones in mares that were presented without noticeable clinical signs. Key clinical message: The unusual presentation of fetal maceration in these mares (only a few fetal bones and no noticeable clinical signs) brings attention to the potential insidious nature of fetal retention. It highlights the importance of a thorough reproductive examination before breeding, along with careful and ongoing monitoring after breeding and throughout pregnancy.

Macération fœtale et rétention partielle d'os fœtaux chez 2 juments. L'interruption de gestation après le Jour 40 chez les juments résulte généralement par l'expulsion (avortement) du fœtus et des membranes fœtales. Toutefois, une rétention fœtale dans l'utérus est également un résultat possible, entraînant soit une momification ou une macération fœtale. La macération fœtale est la décomposition septique des tissus fœtaux à l'intérieur de l'utérus à la suite d'un échec d'expulsion. Elle nécessite la présence de bactéries et d'oxygène dans l'utérus, résultant probablement d'une ouverture du cervix, et résulte en une autolyse des tissus, laissant uniquement des os fœtaux à l'intérieur de la jument. La macération fœtale est une complication rare de la gestation chez les juments qui est généralement associée avec une histoire récente d'avortement, une décharge vaginale persistante, et la rétention de nombreux os fœtaux. Nous rapportons ici 2 cas de macération fœtale avec rétention de seulement quelques os chez des juments présentées avec aucun signe clinique notable.Message clinique clé :La présentation inhabituelle de macération fœtale chez ces juments (uniquement quelques os fœtaux et aucun signe clinque notable) met en lumière la nature potentiellement insidieuse de la rétention fœtale. Elle souligne l'importance d'un examen reproducteur complet avant l'accouplement, avec un suivi minutieux et continu après l'accouplement et durant toute la gestation.(Traduit par Dr Serge Messier).

Hypoabsorptive surgeries cause limb-dependent changes in the gut endocannabinoidome and microbiome in association with beneficial metabolic effects.

OBJECTIVE: To determine whether the metabolic benefits of hypoabsorptive surgeries are associated with changes in the gut endocannabinoidome (eCBome) and microbiome. METHODS: Biliopancreatic diversion with duodenal switch (BPD-DS) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) were performed in diet-induced obese (DIO) male Wistar rats. Control groups fed a high-fat diet (HF) included sham-operated (SHAM HF) and SHAM HF-pair-weighed to BPD-DS (SHAM HF-PW). Body weight, fat mass gain, fecal energy loss, HOMA-IR, and gut-secreted hormone levels were measured. The levels of eCBome lipid mediators and prostaglandins were quantified in different intestinal segments by LC-MS/MS, while expression levels of genes encoding eCBome metabolic enzymes and receptors were determined by RT-qPCR. Metataxonomic (16S rRNA) analysis was performed on residual distal jejunum, proximal jejunum, and ileum contents. RESULTS: BPD-DS and SADI-S reduced fat gain and HOMA-IR, while increasing glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) levels in HF-fed rats. Both surgeries induced potent limb-dependent alterations in eCBome mediators and in gut microbial ecology. In response to BPD-DS and SADI-S, changes in gut microbiota were significantly correlated with those of eCBome mediators. Principal component analyses revealed connections between PYY, N-oleoylethanolamine (OEA), N-linoleoylethanolamine (LEA), Clostridium, and Enterobacteriaceae_g_2 in the proximal and distal jejunum and in the ileum. CONCLUSIONS: BPD-DS and SADI-S caused limb-dependent changes in the gut eCBome and microbiome. The present results indicate that these variables could significantly influence the beneficial metabolic outcome of hypoabsorptive bariatric surgeries.

EGCG inhibits the inflammation and senescence inducing properties of MDA-MB-231 triple-negative breast cancer (TNBC) cells-derived extracellular vesicles in human adipose-derived mesenchymal stem cells.

BACKGROUND: Triple-negative breast cancer (TNBC) cells' secretome can induce a pro-inflammatory phenotype in human adipose-derived mesenchymal stem cells (hADMSC). This can be prevented by the green tea polyphenol epigallocatechin-3-gallate (EGCG). The impact of EGCG on the paracrine regulation that the extracellular vesicles (EVs) specifically exert within the TNBC secretome remains unknown. METHODS: EVs were obtained from a TNBC-derived serum-starved MDA-MB-231 cell model treated or not with EGCG under normoxic or hypoxic (< 1% O2) culture conditions. RNA-Seq analysis was used to assess the EVs' genetic content. The modulation of inflammatory and senescence markers in hADMSC was evaluated by RT-qPCR using cDNA arrays and validated by immunoblotting. A protein profiler phospho-kinase array was used to explore signaling pathways. RESULTS: While hypoxic culture conditions did not significantly alter the genetic content of MDA-MB-231-secreted EVs, the addition of EGCG significantly modified EVs genetic material at low oxygen tension. Gene expression of cancer-associated adipocyte pro-inflammatory markers CXCL8, CCL2 and IL-1ß was increased in hADMSC treated with EVs. Concomitantly, EVs isolated from MDA-MB-231 treated with EGCG (EGCG-EVs) downregulated CCL2 and IL-1ß, while inducing higher expression of CXCL8 and IL-6 levels. EVs activated CHK-2, c-Jun, AKT and GSK-3ß signaling pathways in hADMSC, whereas EGCG-EVs specifically reduced the latter two as well as the serum starvation-induced senescence markers p21 and ß-galactosidase. Finally, the mitochondrial content within the TNBC cells-derived EVs was found reduced upon EGCG treatment. CONCLUSION: This proof of concept study demonstrates that the chemopreventive properties of diet-derived polyphenols may efficiently target the paracrine regulation that TNBC cells could exert upon their surrounding adipose tissue microenvironment.

A Phosphine Oxide-Functionalized Cyclam as a Specific Copper(II) Chelator.

Although cyclam-based ligands are among the strongest copper(II) chelators available, they also usually present good affinity for other divalent cations [Zn(II), Ni(II), and Co(II)], with no copper(II)-specific cyclam ligands having been described so far. As such a property is highly desirable in a wide range of applications, we present herein two novel phosphine oxide-appended cyclam ligands that could be efficiently synthesized through Kabachnik-Fields type reactions on protected cyclam precursors. Their copper(II) coordination properties were closely studied by different physicochemical techniques [electron paramagnetic resonance (EPR) and ultraviolet-visible (UV-vis) spectroscopies, X-ray diffraction, and potentiometry]. The mono(diphenylphosphine oxide)-functionalized ligand demonstrated a copper(II)-specific behavior, unprecedented within the cyclam family of ligands. This was evidenced by UV-vis complexation and competition studies with the parent divalent cations. Density functional theory calculations also confirmed that the particular ligand geometry in the complexes strongly favors copper(II) coordination over that of competing divalent cations, rationalizing the specificity observed experimentally.

Preliminary Validation Study of the French-Quebec Version of the Mild Behavioral Impairment Checklist.

BACKGROUND: Alzheimer disease dementia may be preceded by cognitive stages during which behavioral and psychological changes can occur. More precisely, behavioral symptoms may be observed during the subjective cognitive decline (SCD) or the mild cognitive impairment (MCI) stages; these symptoms can be measured using the Mild Behavioral Impairment Checklist (MBI-C). OBJECTIVE: To validate the French-Quebec version of the MBI-C in individuals ages 60-85 years. METHOD: The sample included 60 participants (20 MCI, 20 SCD, 20 cognitively healthy) and their informants. To assess the discriminant validity of the MBI-C, a Kruskal-Wallis analysis with a multiple comparisons test was performed on the MBI-C Total score. To determine convergent validity, Spearman correlations were calculated between the MBI-C subscales and a set of validation tools. Finally, test-retest reliability was assessed with Spearman correlations of MBI-C scores between two test sessions. RESULTS: All of the analyses indicated satisfactory psychometric properties for the French-Quebec version of the MBI-C. CONCLUSION: This validation study reveals that the MBI-C can be used successfully in dementia risk assessments. From now on, the use of a validated MBI-C will be possible in the French-Quebec population.

Etoposide hypersensitivity reactions associated with in-line filter use: A retrospective cohort study at CHU de Québec-Université Laval.

INTRODUCTION: A case series of hypersensitivity reactions (HSRs) during intravenous administration of etoposide was observed following the introduction of in-line filters (ILFs) at a specialized university-affiliated center. This raised questions about the possible involvement of filters in these reactions. Despite there being very little published evidence to inform clinical decision making in this potentially clinically significant situation, the use of ILFs was discontinued at this center pending further investigation. The aims of this study were to evaluate the cumulative incidence of etoposide-related HSR with and without the use of ILF and to describe the reactions in adult and pediatric patients with cancer. METHODS: A retrospective cohort study was performed among all pediatric and adult patients treated with intravenous etoposide at a maximal concentration of 0.4 mg/mL at our center between 30 September 2015 and 16 August 2018. This covered periods of time during which ILFs were used, as well as 6 months before their implementation and after their withdrawal. Data were extracted from medical records and cumulative incidence was calculated for each of the time periods (pre-ILF, ILF, and post-ILF) as the proportion of patients who recorded an HSR (one or more). Confidence intervals were calculated for each proportion using Fisher's Exact 95%. Comparisons of proportions between time periods were performed using Exact Pearson Chi-squared tests. Data were stratified by a number of perfusion cycles (single cycle or multiple cycles) and by patient population (adult and pediatric). RESULTS: A total of 284 patients were included in the study. The overall cumulative incidence of etoposide HSR was 9.9%. The cumulative incidence of HSR tended to be higher during ILF use when compared with combined pre- and post-ILF periods (12.2% [95% CI: 7.9-17.8] vs. 5.2% [95% CI: 1.7-11.7], p = 0.09). In patients who received multiple cycles of etoposide, the cumulative incidence of HSRs was higher during ILF use when compared with combined pre- and post-ILF periods (15.0% [95% CI: 9.6-21.8] vs. 3.9% [95% CI: 0.8-11.0], p = 0.01). The majority of HSRs' maximal severity were grade 1 or 2 (85.7%) according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. CONCLUSIONS: This study suggests a link between the use of ILFs and increased incidence of HSR during etoposide perfusion.

Ethical Implications of Artificial Intelligence in Population Health and the Public's Role in Its Governance: Perspectives From a Citizen and Expert Panel.

BACKGROUND: Artificial intelligence (AI) systems are widely used in the health care sector. Mainly applied for individualized care, AI is increasingly aimed at population health. This raises important ethical considerations but also calls for responsible governance, considering that this will affect the population. However, the literature points to a lack of citizen participation in the governance of AI in health. Therefore, it is necessary to investigate the governance of the ethical and societal implications of AI in population health. OBJECTIVE: This study aimed to explore the perspectives and attitudes of citizens and experts regarding the ethics of AI in population health, the engagement of citizens in AI governance, and the potential of a digital app to foster citizen engagement. METHODS: We recruited a panel of 21 citizens and experts. Using a web-based survey, we explored their perspectives and attitudes on the ethical issues of AI in population health, the relative role of citizens and other actors in AI governance, and the ways in which citizens can be supported to participate in AI governance through a digital app. The responses of the participants were analyzed quantitatively and qualitatively. RESULTS: According to the participants, AI is perceived to be already present in population health and its benefits are regarded positively, but there is a consensus that AI has substantial societal implications. The participants also showed a high level of agreement toward involving citizens into AI governance. They highlighted the aspects to be considered in the creation of a digital app to foster this involvement. They recognized the importance of creating an app that is both accessible and transparent. CONCLUSIONS: These results offer avenues for the development of a digital app to raise awareness, to survey, and to support citizens' decision-making regarding the ethical, legal, and social issues of AI in population health.

Consistent gut bacterial and short-chain fatty acid signatures in hypoabsorptive bariatric surgeries correlate with metabolic benefits in rats.

OBJECTIVE: The study aimed at comparing how changes in the gut microbiota are associated to the beneficial effects of the most clinically efficient hypoabsorptive bariatric procedures, namely Roux-en-Y gastric bypass (RYGB), biliopancreatic diversion with duodenal switch (BPD-DS) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S). METHODS: Diet-induced obese (DIO) male Wistar rats were divided into seven groups. In addition to the groups subjected to RYGB, BPD-DS and SADI-S, the following four control groups were included: SHAM-operated rats fed a high-fat diet (SHAM HF), SHAM fed a low-fat diet (SHAM LF), SHAM HF-pair-weighed to BPD-DS (SHAM HF-PW) and sleeve-gastrectomy (SG) rats. Body weight, food intake, glucose tolerance, insulin sensitivity/resistance, and L-cell secretion were assessed. The gut microbiota (16 S ribosomal RNA gene sequencing) as well as the fecal and cæcal contents of short-chain fatty acids (SCFAs) were also analyzed prior to, and after the surgeries. RESULTS: The present study demonstrates the beneficial effect of RYGB, BPD-DS and SADI-S on fat mass gain and glucose metabolism in DIO rats. These benefits were proportional to the effect of the surgeries on food digestibility (BPD-DS > SADI-S > RYGB). Notably, hypoabsorptive surgeries led to consonant microbial signatures characterized by decreased abundance of the Ruminococcaceae (Oscillospira and Ruminococcus), Oscillospiraceae (Oscillibacter) and Christensenellaceae, and increased abundance of the Clostridiaceae (Clostridium), Sutterellaceae (Sutterella) and Enterobacteriaceae. The gut bacteria following hypoabsorptive surgeries were associated with higher fecal levels of propionate, butyrate, isobutyrate and isovalerate. Increases in the fecal SCFAs were in turn positively and strongly correlated with the levels of peptide tyrosine-tyrosine (PYY) and with the beneficial effects of the surgery. CONCLUSION: The present study emphasizes the consistency with which the three major hypoabsorptive bariatric procedures RYGB, BPD-DS and SADI-S create a gut microbial environment capable of producing a SCFA profile favorable to the secretion of PYY and to beneficial metabolic effects.

Valosin-containing protein ATPase activity regulates the morphogenesis of Zika virus replication organelles and virus-induced cell death.

With no available therapies, infections with Zika virus (ZIKV) constitute a major public health concern as they can lead to congenital microcephaly. In order to generate an intracellular environment favourable to viral replication, ZIKV induces endomembrane remodelling and the morphogenesis of replication factories via enigmatic mechanisms. In this study, we identified the AAA+ type ATPase valosin-containing protein (VCP) as a cellular interaction partner of ZIKV non-structural protein 4B (NS4B). Importantly, its pharmacological inhibition as well as the expression of a VCP dominant-negative mutant impaired ZIKV replication. In infected cells, VCP is relocalised to large ultrastructures containing both NS4B and NS3, which are reminiscent of dengue virus convoluted membranes. Moreover, short treatment with the VCP inhibitors NMS-873 or CB-5083 drastically decreased the abundance and size of ZIKV-induced convoluted membranes. Furthermore, NMS-873 treatment inhibited ZIKV-induced mitochondria elongation previously reported to be physically and functionally linked to convoluted membranes in case of the closely related dengue virus. Finally, VCP inhibition resulted in enhanced apoptosis of ZIKV-infected cells strongly suggesting that convoluted membranes limit virus-induced cytopathic effects. Altogether, this study identifies VCP as a host factor required for ZIKV life cycle and more precisely, for the maintenance of viral replication factories. Our data further support a model in which convoluted membranes regulate ZIKV life cycle by impacting on mitochondrial functions and ZIKV-induced death signals in order to create a cytoplasmic environment favourable to viral replication.

Flaviviridae and mitochondria: Everything you always wanted to know about their relationship but were afraid to ask.

Infections with Flaviviridae constitute a major public health concern, especially considering the limited availability of prophylactic and therapeutic treatments. Most notably, the recent emergence of Zika virus in the Americas was associated with the dramatic increase of severe symptoms such as congenital microcephaly, while hepatitis C virus causes the death of approximately 300,000 individuals annually. Flaviviridae have evolved to hijack cellular organelles and to favor their replication, often via divergent molecular mechanisms. In addition to the remodeling of the endoplasmic reticulum, which is required for the replication of the viral genome and the assembly of the neosynthesized virions, Flaviviridae induce drastic morphological alterations of the mitochondria. This is associated with the viral co-opting of several key mitochondrial functions in apoptosis, innate immunity and metabolism. This review recapitulates the current knowledge about the morphological and functional relationship between Flaviviridae and mitochondria and explains how this contributes to the establishment of a cytoplasmic environment which is favorable to viral replication.

[Flaviviridae and mitochondria: Everything you always wanted to know about their relationship but were afraid to ask]. / Flaviviridae et mitochondries : tout ce que vous avez toujours voulu savoir sur leur relation sans jamais oser le demander.

Infections with Flaviviridae constitute a major public health concern, especially considering the limited availability of prophylactic and therapeutic treatments. Most notably, the recent emergence of Zika virus in the Americas was associated with the dramatic increase of severe symptoms such as congenital microcephaly, while hepatitis C virus causes the death of approximately 300,000 individuals annually. Flaviviridae have evolved to hijack cellular organelles and to favor their replication, often by divergent molecular mechanisms. In addition to the remodeling of the endoplasmic reticulum, which is required for the replication of the viral genome and the assembly of the neosynthetized virions, Flaviviridae induce drastic morphological alterations of the mitochondria. This is associated with the viral co-opting of several key mitochondrial functions in apoptosis, innate immunity and metabolism. This review recapitulates the current knowledge about the morphological and functional relationship between Flaviviridae and mitochondria and explains how this contributes to the establishment of a cytoplasmic environment which is favorable to viral replication.

Barriers and Facilitators to Implementing Community Outreach Work, and Inter-professional Collaboration with Regional Partners.

Community outreach workers support individuals in accessing the health and community services they require through various forms of proximity approaches. Even though community outreach has been available in the province of Quebec (Canada) for the past 40 years, it is still difficult to implement and sustain, especially with families of young children. The aim of this study was to document barriers and facilitators to implementing community outreach practices, and to describe how such workers collaborate with sectoral (e.g. health care) and inter-sectoral (e.g. municipalities, community organizations, schools) partners. We performed a content analysis on 55 scientific and grey literature documents, and transcriptions of 24 individual interviews and 3 focus groups with stakeholders including parents, community outreach workers, health care employees, and inter-sectoral partners. This study reveals four categories of barriers and facilitators to the implementation of community outreach work (i.e. organizational factors, nature of the work and worker-related factors, family-related factors, external factors). With regards to collaboration, community outreach workers deal with various partners. Good inter-professional collaboration is achieved through positive interactions and communication, shared or co-developed activities for the families, co-intervention with families, and strategies to enhance role awareness and inter-sectoral meetings. Results highlighted that many factors interact and can either influence, positively or negatively, the opportunity to implement community outreach work. The collaborative practices identified may help to maximize facilitators and overcome barriers. Advocacy and a better understanding of how to integrate community outreach work within health services while maintaining the workers' flexibility are needed to sustain this practice.

Phase Transformation and Roughening in Artificially Aged and Retrieved Zirconia-Toughened Alumina Femoral Heads.

BACKGROUND: Zirconia-toughened alumina (ZTA) used in hip arthroplasty contains yttria-stabilized zirconia (Y-TZP) as a toughening agent. However, Y-TZP is well known to degrade in vivo from tetragonal to monoclinic phase transformation. The stability of never-implanted ZTA femoral heads was evaluated in a severe artificial aging test, with retrieved ZTA heads also evaluated for clinical relevance. We hypothesized that ZTA would degrade due to tetragonal-to-monoclinic phase transformation, with changes in surface topography and progressive roughening. Y-TZP specimens served as a positive comparison group, while magnesia-stabilized zirconia (Mg-PSZ), which does not undergo phase transformation, served as a stable comparison group. METHODS: Monoclinic phase concentration, surface topography, and roughness of never-implanted ZTA, Y-TZP, and Mg-PSZ heads were measured by X-ray diffraction and optical profilometry, before and after 2 rounds of 24 hours of hydrothermal aging. Explanted ZTA heads were characterized by the same methods. RESULTS: After 48 hours in an autoclave, the surface of ZTA heads exhibited irregularly spaced protrusions about 20-30 nm high by 100-150 µm in diameter, with significant increases in monoclinic phase concentration (from 12.2% to 21.3%) and surface roughness. Similar features were observed on the surface of explanted ZTA heads, with 33% monoclinic phase after 2.7 years in vivo. CONCLUSION: Based on data collected from ZTA retrievals, this artificial aging test underestimated the amount of phase transformation in vivo. Phase transformation and surface roughening of ZTA heads steadily increased without reaching a plateau, which may lead to stress concentrations and weakening of the ceramic material, and could result in late fracture and wear.

Do plasma protein:fibrinogen ratios in horses provide additional information compared with fibrinogen concentration alone?

The plasma protein:fibrinogen (PP:F) ratio was introduced to aid interpretation of hyperfibrinogenemia by accounting for dehydration. However, this ratio is inconsistently assessed in practice and its clinical value remains unknown. Our objective was to determine whether the PP:F ratio provides additional information in adult horses beyond fibrinogen concentration alone. Two databases were reviewed to identify 412 hyperfibrinogenemic horses. Plasma protein:fibrinogen ratios were calculated and their interpretation compared to the fibrinogen concentration. Ratios < 15 were supportive of inflammation. Albumin and total protein concentrations were evaluated when ratios were ≥ 15 to determine if inflammation was supported. Very good agreement (86%) was found on the presence of inflammation when PP:F ratios were compared to fibrinogen concentration. In 72% of cases in which PP:F ratios did not support inflammation, inflammation was considered likely based on albumin and total protein. These findings suggest that PP:F ratios do not provide additional information in horses over fibrinogen concentrations alone.

Est-ce que le ratio plasma protéine:fibrinogène chez les chevaux amène une information additionnelle par rapport à la seule concentration en fibrinogène? Le ratio plasma protéine: fibrinogène (PP:F) a été introduit pour aider à l'interprétation de l'hyperfibrinogénémie lors d'hémoconcentration. Toutefois, la valeur clinique de ce ratio est inconnue. Notre objectif était de déterminer si le ratio amène une information additionnelle comparé au fibrinogène. Deux bases de données ont été revues pour identifier 412 chevaux hyperfibrinogénémiques. Le ratio a été calculé et son interprétation comparée à celle du fibrinogène. Les ratios < 15 suggèrent l'inflammation. Pour les cas présentant un ratio ≥ 15, la concentration en albumine et protéines totales a été revue pour voir si l'inflammation était possible. Nos résultats indiquent que dans 86 % des cas, le ratio et le fibrinogène suggèrent la présence d'inflammation. Pour 72 % des cas où le ratio ne suggère pas l'inflammation, cette dernière est considérée probable étant donné la concentration en protéines totales et albumine. Ces résultats suggèrent que le ratio PP:F n'apporte pas d'information supplémentaire comparé au fibrinogène.(Traduit par les auteurs).