Do Acoustic Characteristics of Dysarthria in People With Parkinson's Disease Differ Across Languages?

PURPOSE: Cross-language studies suggest more similarities than differences in how dysarthria affects the speech of people with Parkinson's disease (PwPD) who speak different languages. In this study, we aimed to identify the relative contribution of acoustic variables to distinguish PwPD from controls who spoke varieties of two Romance languages, French and Portuguese. METHOD: This bi-national, cross-sectional, and case-controlled study included 129 PwPD and 124 healthy controls who spoke French or Portuguese. All participants underwent the same clinical examinations, voice/speech recordings, and self-assessment questionnaires. PwPD were evaluated off and on optimal medication. Inferential analyses included Disease (controls vs. PwPD) and Language (French vs. Portuguese) as factors, and random decision forest algorithms identified relevant acoustic variables able to distinguish participants: (a) by language (French vs. Portuguese) and (b) by clinical status (PwPD on and off medication vs. controls). RESULTS: French-speaking and Portuguese-speaking individuals were distinguished from each other with over 90% accuracy by five acoustic variables (the mean fundamental frequency and the shimmer of the sustained vowel /a/ production, the oral diadochokinesis performance index, the relative sound level pressure and the relative sound pressure level standard deviation of the text reading). A distinct set of parameters discriminated between controls and PwPD: for men, maximum phonation time and the oral diadochokinesis speech proportion were the most significant variables; for women, variables calculated from the oral diadochokinesis were the most discriminative. CONCLUSIONS: Acoustic variables related to phonation and voice quality distinguished between speakers of the two languages. Variables related to pneumophonic coordination and articulation rate were the more effective in distinguishing PwPD from controls. Thus, our research findings support that respiration and diadochokinesis tasks appear to be the most appropriate to pinpoint signs of dysarthria, which are largely homogeneous and language-universal. In contrast, identifying language-specific variables with the speech tasks and acoustic variables studied was less conclusive.

Green synthesis of (R)-3-hydroxy-decanoic acid and analogs from levoglucosenone: a novel access to the fatty acid moiety of rhamnolipids.

Rhamnolipids (RLs) are highly valuable molecules in the cosmetic, pharmaceutic, and agricultural sectors with outstanding biosurfactant properties. In agriculture, due to their potential to artificially stimulate the natural immune system of crops (also known as elicitation), they could represent a critical substitute to conventional pesticides. However, their current synthesis methods are complex and not aligned with green chemistry principles, posing a challenge for their industrial applications. In addition, their bioproduction is cumbersome with reproducibility issues and expensive downstream processing. This work offers a more straightforward and green access to RLs, crucial to decipher their mechanisms of action and design novel potent and eco-friendly elicitors. To achieve this, we propose an efficient seven-step synthetic pathway toward (R)-3-hydroxyfatty acid chains present in RLs, starting from cellulose-derived levoglucosenone, with Michael addition, Baeyer-Villiger oxidation, Bernet-Vasella reaction, and cross-metathesis homologation as key steps. This method allowed the production of (R)-3-hydroxyfatty acid chains and derivatives with an overall yield ranging from 24% to 36%.

ORCA-EFCD consensus report on clinical recommendations for caries diagnosis. Paper III: caries diagnosis at the individual level.

The aim of the present consensus paper was to provide recommendations for clinical practice on the individual etiological and modifying factors to be assessed in the individual diagnosis of caries, and the methods for their assessment, supporting personalized treatment decisions. The executive councils of the European Organisation for Caries Research (ORCA) and the European Federation of Conservative Dentistry (EFCD) nominated ten experts each to join the expert panel. The steering committee formed three work groups which were asked to provide recommendations on 1) caries detection and diagnostic methods, 2) caries activity assessment and 3) forming individualised caries diagnoses. The experts responsible for "individualised caries diagnosis" searched and evaluated the relevant literature, drafted this manuscript and made provisional consensus recommendations. These recommendations were discussed and refined during the structured process in the whole work group. Finally, the agreement for each recommendation was determined using an anonymous eDelphi survey. The threshold for approval of recommendations was determined at 70% agreement. Ten recommendations were approved and agreed by the whole expert panel, covering medical history, caries experience, plaque, diet, fluoride and saliva. While the level of evidence was low, the level of agreement was typically very high, except for one recommendation on salivary flow measurement, where 70% agreed. It is recommended that all aspects of caries lesion progression and activity, recent caries experience, medical conditions and medications, plaque, diet, fluoride and saliva should be synthesized to arrive at an individual diagnosis. The expert panel merged evidence from existing guidelines and scientific literature with practical considerations and provided recommendations for their use in daily dental practice.

Lats1 and Lats2 regulate YAP and TAZ activity to control the development of mouse Sertoli cells.

Recent reports suggest that the Hippo signaling pathway regulates testis development, though its exact roles in Sertoli cell differentiation remain unknown. Here, we examined the functions of the main Hippo pathway kinases, large tumor suppressor homolog kinases 1 and 2 (Lats1 and Lats2) in developing mouse Sertoli cells. Conditional inactivation of Lats1/2 in Sertoli cells resulted in the disorganization and overgrowth of the testis cords, the induction of a testicular inflammatory response and germ cell apoptosis. Stimulated by retinoic acid 8 (STRA8) expression in germ cells additionally suggested that germ cells may have been preparing to enter meiosis prior to their loss. Gene expression analyses of the developing testes of conditional knockout animals further suggested impaired Sertoli cell differentiation, epithelial-to-mesenchymal transition, and the induction of a specific set of genes associated with Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ)-mediated integrin signaling. Finally, the involvement of YAP/TAZ in Sertoli cell differentiation was confirmed by concomitantly inactivating Yap/Taz in Lats1/2 conditional knockout model, which resulted in a partial rescue of the testicular phenotypic changes. Taken together, these results identify Hippo signaling as a crucial pathway for Sertoli cell development and provide novel insight into Sertoli cell fate maintenance.

Short- and long-term morbidity after Taylor flap (oblique rectus abdominis flap) for perineal reconstruction after abdominoperineal resection: A single-center series of 140 patients.

BACKGROUND: Abdominoperineal resection (APR) leads to a substantial loss of tissue and a high rate of complications. The Taylor flap is a musculocutaneous flap used in reconstruction after APR. OBJECTIVES: We aimed to analyze the short and long-term morbidity of reconstruction with a Taylor flap (oblique rectus abdominis flap) after APR and to identify the risk factors for postoperative complications. METHODS: We retrospectively included all patients who had undergone APR with immediate reconstruction with a Taylor flap in our department between July 2000 and June 2018. Demographics, oncological data, treatment, and short- and long-term morbidity were reviewed. RESULTS: Among the 140 patients included, we identified early minor complications in 42 patients (30%) and 14 early major complications (10%). Total necrosis of the flap requiring its removal occurred in four patients (2.8%). Eleven patients (7.9%) presented with a midline incision hernia, and seven (5%) presented with a subcostal incision hernia. No perineal hernia was found. No risk factors for the complications were identified. CONCLUSION: The Taylor flap is a safe procedure with few complications and limited donor site morbidity. Moreover, it prevents perineal hernias. These results confirm that the Taylor flap is a well-suited procedure for reconstruction after APR.

Monitoring monocyte HLA-DR expression and CD4 + T lymphocyte count in dexamethasone-treated severe COVID-19 patients.

BACKGROUND: A 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented. RESULTS: To analyze monocyte HLA-DR expression (mHLA-DR) and CD4 + T lymphocyte count (CD4) in critically ill COVID-19 patients after a dexamethasone course and evaluate their association with 28-day ICU mortality, adult COVID-19 patients (n = 176) with an ICU length of stay of at least 10 days and under dexamethasone treatment were included. Associations between each biomarker value (or in combination) measured at day 10 after ICU admission and 28-day mortality in ICU were evaluated. At day 10, the majority of patients presented decreased values of both parameters. A significant association between low mHLA-DR and 28-day mortality was observed. This association remained significant in a multivariate analysis including age, comorbidities or pre-existing immunosuppression (adjusted Hazard ratio (aHR) = 2.86 [1.30-6.32], p = 0.009). Similar results were obtained with decreased CD4 + T cell count (aHR = 2.10 [1.09-4.04], p = 0.027). When combining these biomarkers, patients with both decreased mHLA-DR and low CD4 presented with an independent and significant elevated risk of 28-day mortality (i.e., 60%, aHR = 4.83 (1.72-13.57), p = 0.001). CONCLUSIONS: By using standardized immunomonitoring tools available in clinical practice, it is possible to identify a subgroup of patients at high risk of mortality at the end of a 10-day dexamethasone treatment. This emphasizes the significance of integrating immune monitoring into the surveillance of intensive care patients in order to guide further immumodulation approaches.

Tooth wear and bruxism: A scoping review.

OBJECTIVE: This study presents a scoping review to determine the association between tooth wear and bruxism. DATA: A protocol was developed a priori (Open Science Framework (DOI 10.17605/OSF.IO/CS7JX)). Established scoping review methods were used for screening, data extraction, and synthesis. Risk of bias was assessed using JBI tools. Direct associations between tooth wear and bruxism were assessed. SOURCES: Embase, SCOPUS, Web of Science, Cochrane, and PubMed were searched. STUDY SELECTION: Any clinical study containing tooth wear and bruxism assessment done on humans in any language was included. Animal, in-vitro studies and case reports were excluded. CONCLUSIONS: Thirty publications reporting on the association between tooth wear and bruxism were included. The majority of publications were cross-sectional studies (90%) while only three were longitudinal (10%). Eleven papers assessed definitive bruxism for analysis (instrumental tools), one paper assessed probable bruxism (clinical inspection with self-report) and eighteen assessed possible bruxism (self-report). Of the eleven papers assessing definitive bruxism, eight also reported outcomes of non-instrumental tools. Tooth wear was mostly scored using indexes. Most studies reported no or weak associations between tooth wear and bruxism, except for the studies done on cervical tooth wear. When bruxism assessment was done through self-report, more often an association was found. Studies using multivariate analyses did not find an association between tooth wear and bruxism, except the cervical wear studies. Evidence shows inconclusive results as to whether bruxism and tooth wear are related or not. Therefore, well-designed longitudinal trials are needed to address this gap in the literature. CLINICAL SIGNIFICANCE: Based on the evidence, dental clinicians should not infer bruxism activity solely on the presence of tooth wear.

Tacrolimus Monitoring in Liver Transplant Recipients, Posttransplant Cholestasis: A Comparative Between 2 Commercial Immunoassays and a Liquid Chromatography-Tandem Mass Spectrometry Method.

BACKGROUND: Cholestasis commonly occurs after orthotopic liver transplantation. It can be extrahepatic because of mechanical obstruction or intrahepatic because of various causes. During cholestasis episodes, blood concentrations of tacrolimus (TAC) metabolites may increase, potentially affecting TAC concentrations measured by immunoassays. This study aimed to simultaneously evaluate the analytical performance of 2 TAC immunoassays, a quantitative microsphere system (QMS) immunoassay, and chemiluminescence microparticle immunoassay, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a reference method in liver transplant recipients. METHODS: This single-center study included 265 patients who underwent orthotopic liver transplantation. In total, 942 blood samples were collected. TAC trough concentrations were measured using LC-MS/MS and 2 immunoassays in parallel. The plasma concentrations of conjugated bilirubin were measured in all samples. The results were analyzed using Bland-Altman plots and Passing-Bablok regressions. RESULTS: The Bland-Altman plot analysis showed that the TAC QMS immunoassay has a significant bias (+37%) compared with LC-MS/MS, and this bias was higher in patients with cholestasis with hyperbilirubinemia (≤+70% in patients with conjugated bilirubin >150 µmol/L). In comparison, the chemiluminescence microparticle immunoassay showed acceptable analytical performance in patients with hyperbilirubinemia (bias <10%). CONCLUSIONS: In agreement with previous findings, the TAC QMS immunoassay showed a positive bias compared with LC-MS/MS. This bias is remarkably high in patients with cholestasis and hyperbilirubinemia, suggesting the cross-reactivity of TAC metabolites with the monoclonal antibody used in the QMS immunoassay.

Real-life use of letermovir prophylaxis for cytomegalovirus in heart transplant recipients.

INTRODUCTION: Cytomegalovirus (CMV) remains the predominant opportunistic infection following solid organ transplantation (SOT). While valganciclovir is the drug of choice for CMV prophylaxis, its utility can be compromised due to the risk of cytopenia. Letermovir, a novel agent approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients and high-risk kidney transplant recipients, exhibits reduced toxicity. This study aims to present the practical application of letermovir as both primary and secondary prophylaxis against CMV in heart transplant recipients (HTR). METHODS: In this observational, retrospective, single-center study, we included all consecutive adult HTRs from June 2020 to January 2022 who were administered letermovir for CMV prophylaxis. We documented instances of CMV breakthrough infections, side effects related to letermovir, changes in neutropenia following the switch from valganciclovir to letermovir, and any drug interactions with the immunosuppressive regimen. RESULTS: The study comprised 10 patients: two received primary prophylaxis with letermovir due to a high risk of CMV infection (donor-positive, recipient-negative serostatus), and eight received it as secondary prophylaxis following a CMV infection. The median duration of letermovir administration was 8 months (range 3-12 months). No CMV breakthrough infections were reported while on prophylaxis. However, three patients experienced CMV breakthrough infections after discontinuing letermovir prophylaxis (30%). No significant side effects were observed, although one patient reported digestive intolerance. Among the nine patients on tacrolimus, six needed reduced doses after switching to letermovir. CONCLUSION: This real-life study appears to support the effectiveness of letermovir prophylaxis in HTR. Nonetheless, the risk of CMV infection post-treatment cessation is notable. Further drug monitoring and research on the efficacy of letermovir for CMV prophylaxis in SOT patients is warranted.

ORCA-EFCD consensus report on clinical recommendations for caries diagnosis. Paper II: caries lesion activity and progression assessment.

INTRODUCTION: This consensus paper provides recommendations for oral health professionals on why and how to assess caries activity and progression with special respect to the site of a lesion. METHODS: An expert panel was nominated by the executive councils of the European Organization for Caries Research (ORCA) and the European Federation of Conservative Dentistry (EFCD). The steering committee built three working groups that were asked to provide recommendations on 1) caries detection and diagnostic methods, 2) caries activity and progression assessment and 3) obtain individualized caries diagnoses. The experts of work group 2 phrased and agreed on provisional general and specific recommendations on caries lesion activity and progression, based on a review of the current literature. These recommendations were then discussed and refined in a consensus workshop followed by an anonymous Delphi survey to determine the agreement on each recommendation. RESULTS: The expert panel agreed on general (n=7) and specific recommendations (n=6). The specific recommendations cover coronal caries on pits and fissures, smooth surfaces, proximal surfaces, as well as root caries and secondary caries/ caries adjacent to restorations and sealants (CARS). 3/13 recommendations yielded perfect agreement. CONCLUSION: The most suitable method for lesion activity assessment is the visual-tactile method. No single clinical characteristic is indicative of lesion activity; instead, lesion activity assessment is based on assessing and weighing several clinical signs. The recall intervals for visual and radiographic examination need to be adjusted to the presence of active caries lesions and recent caries progression rates. Modifications should be based on individual patient characteristics.

[Chemotherapy-induced nausea and vomiting in pediatric oncology patients: 2023 recommendations from the Supportive Care Committee of the French Society of Cancer in Children and Adolescents]. / Nausées et vomissements chimio-induits en oncohématologie pédiatrique : actualisation 2023 des recommandations du comité soins de support de la SFCE.

Chemotherapy-induced nausea and vomiting (CINV) are frequent and dreaded side effects in cancer treatments. CINV has a major impact on patient's condition and quality of life. Prophylaxis is tailored to patient's profile and the emetogenic level of their chemotherapy. The aim of this study is to update the recommendations for CINV prevention and management in pediatric onco-hematology for use in France, by adapting the guidelines of the Pediatric Oncology Group of Ontario (POGO). Clinical practice guideline adaptation is a recognized method for tailoring existing clinical practice guidelines to local context. A multidisciplinary French-speaking panel was formed to discuss about POGO guideline recommendations for the acute and delayed phases, breakthrough, refractory and anticipatory CINV and the evidence supporting them. Panel members were asked whether they wanted to adopt, modify or reject each of the POGO guideline recommendations. Panel members translated each recommendation and adapted recommendations for an implementation in France. Their acceptance required agreement at least 80 % of panel members. Algorithms and tables were created, listing all the recommendations and providing a better overview for decision-making process adapted to the patient's profile. These recommendations should be reviewed for implementation at French institutions caring for pediatric cancer patients and once implemented, the rates of adherence to recommendations and CINV control should be reported.

The biological controls of soil carbon accumulation following wildfire and harvest in boreal forests: A review.

Boreal forests are frequently subjected to disturbances, including wildfire and clear-cutting. While these disturbances can cause soil carbon (C) losses, the long-term accumulation dynamics of soil C stocks during subsequent stand development is controlled by biological processes related to the balance of net primary production (NPP) and outputs via heterotrophic respiration and leaching, many of which remain poorly understood. We review the biological processes suggested to influence soil C accumulation in boreal forests. Our review indicates that median C accumulation rates following wildfire and clear-cutting are similar (0.15 and 0.20 Mg ha-1 year-1, respectively), however, variation between studies is extremely high. Further, while many individual studies show linear increases in soil C stocks through time after disturbance, there are indications that C stock recovery is fastest early to mid-succession (e.g. 15-80 years) and then slows as forests mature (e.g. >100 years). We indicate that the rapid build-up of soil C in younger stands appears not only driven by higher plant production, but also by a high rate of mycorrhizal hyphal production, and mycorrhizal suppression of saprotrophs. As stands mature, the balance between reductions in plant and mycorrhizal production, increasing plant litter recalcitrance, and ectomycorrhizal decomposers and saprotrophs have been highlighted as key controls on soil C accumulation rates. While some of these controls appear well understood (e.g. temporal patterns in NPP, changes in aboveground litter quality), many others remain research frontiers. Notably, very little data exists describing and comparing successional patterns of root production, mycorrhizal functional traits, mycorrhizal-saprotroph interactions, or C outputs via heterotrophic respiration and dissolved organic C following different disturbances. We argue that these less frequently described controls require attention, as they will be key not only for understanding ecosystem C balances, but also for representing these dynamics more accurately in soil organic C and Earth system models.

ORCA-EFCD consensus report on clinical recommendation for caries diagnosis. Paper I: caries lesion detection and depth assessment.

OBJECTIVES: The aim of the present consensus paper was to provide recommendations for clinical practice considering the use of visual examination, dental radiography and adjunct methods for primary caries detection. MATERIALS AND METHODS: The executive councils of the European Organisation for Caries Research (ORCA) and the European Federation of Conservative Dentistry (EFCD) nominated ten experts each to join the expert panel. The steering committee formed three work groups that were asked to provide recommendations on (1) caries detection and diagnostic methods, (2) caries activity assessment and (3) forming individualised caries diagnoses. The experts responsible for "caries detection and diagnostic methods" searched and evaluated the relevant literature, drafted this manuscript and made provisional consensus recommendations. These recommendations were discussed and refined during the structured process in the whole work group. Finally, the agreement for each recommendation was determined using an anonymous Delphi survey. RESULTS: Recommendations (N = 8) were approved and agreed upon by the whole expert panel: visual examination (N = 3), dental radiography (N = 3) and additional diagnostic methods (N = 2). While the quality of evidence was found to be heterogeneous, all recommendations were agreed upon by the expert panel. CONCLUSION: Visual examination is recommended as the first-choice method for the detection and assessment of caries lesions on accessible surfaces. Intraoral radiography, preferably bitewing, is recommended as an additional method. Adjunct, non-ionising radiation methods might also be useful in certain clinical situations. CLINICAL RELEVANCE: The expert panel merged evidence from the scientific literature with practical considerations and provided recommendations for their use in daily dental practice.

Challenges in the Monitoring of Therapeutic Plasma Exchange during Acute Heparin-Induced Thrombocytopenia in Adults under ECMO.

Therapeutic plasma exchange (TPE) has been proposed to remove heparin-induced thrombocytopenia (HIT) antibodies before planned thoracic surgery in patients with acute HIT and to allow brief re-exposure to heparin during surgery. In patients on extracorporeal membrane oxygenation (ECMO), simultaneous administration of TPE and alternative nonheparin anticoagulant therapies is challenging. We report 2 patients on ECMO with acute HIT who underwent repeated TPE to enable cardiothoracic surgery with the use of heparin. In both cases, serial monitoring of HIT antibody titer and heparin-induced platelet activation assay (HIPA) was performed. The effect of adding exogenous platelet factor 4 (PF4) in the HIPA was also tested. Negative anti-PF4/H IgG levels were achieved after 5 and 3 TPE sessions, respectively and patients could beneficiate from surgery with brief heparin re-exposure without any thrombotic complication. Negative HIPA results were obtained before negative anti-PF4/H IgG in one patient but remained positive in the other despite very low antibody titers. The addition of PF4 in HIPA led to more contrasted results for the two patients. Serial HIT screening including immunological and functional assays is necessary to closely monitor TPE in acute HIT patients on ECMO who require surgery. The addition of PF4 in HIPA could help detect clinically relevant platelet-activating antibodies and guide re-exposure to heparin.

Lifestyle Factors and Breast Cancer in Females with PTEN Hamartoma Tumor Syndrome (PHTS).

Females with PTEN Hamartoma Tumor Syndrome (PHTS) have breast cancer risks up to 76%. This study assessed associations between breast cancer and lifestyle in European female adult PHTS patients. Data were collected via patient questionnaires (July 2020-March 2023) and genetic diagnoses from medical files. Associations between lifestyle and breast cancer were calculated using logistic regression corrected for age. Index patients with breast cancer before PHTS diagnosis (breast cancer index) were excluded for ascertainment bias correction. In total, 125 patients were included who completed the questionnaire at a mean age of 44 years (SD = 13). This included 21 breast cancer indexes (17%) and 39 females who developed breast cancer at 43 years (SD = 9). Breast cancer patients performed about 1.1 times less often 0-1 times/week physical activity than ≥2 times (ORtotal-adj = 0.9 (95%CI 0.3-2.6); consumed daily about 1.2-1.8 times more often ≥1 than 0-1 glasses of alcohol (ORtotal-adj = 1.2 (95%CI 0.4-4.0); ORnon-breastcancer-index-adj = 1.8 (95%CI 0.4-6.9); were about 1.04-1.3 times more often smokers than non-smokers (ORtotal-adj = 1.04 (95%CI 0.4-2.8); ORnon-breastcancer-index-adj = 1.3 (95%CI 0.4-4.2)); and overweight or obesity (72%) was about 1.02-1.3 times less common (ORtotal-adj = 0.98 (95%CI 0.4-2.6); ORnon-breastcancer-index-adj = 0.8 (95%CI 0.3-2.7)). Similar associations between lifestyle and breast cancer are suggested for PHTS and the general population. Despite not being statistically significant, results are clinically relevant and suggest that awareness of the effects of lifestyle on patients' breast cancer risk is important.

Low Density Lipoprotein Cholesterol Decreases the Expression of Adenosine A2A Receptor and Lipid Rafts-Protein Flotillin-1: Insights on Cardiovascular Risk of Hypercholesterolemia.

High blood levels of low-density lipoprotein (LDL)-cholesterol (LDL-C) are associated with atherosclerosis, mainly by promoting foam cell accumulation in vessels. As cholesterol is an essential component of cell plasma membranes and a regulator of several signaling pathways, LDL-C excess may have wider cardiovascular toxicity. We examined, in untreated hypercholesterolemia (HC) patients, selected regardless of the cause of LDL-C accumulation, and in healthy participants (HP), the expression of the adenosine A2A receptor (A2AR), an anti-inflammatory and vasodilatory protein with cholesterol-dependent modulation, and Flotillin-1, protein marker of cholesterol-enriched plasma membrane domains. Blood cardiovascular risk and inflammatory biomarkers were measured. A2AR and Flotillin-1 expression in peripheral blood mononuclear cells (PBMC) was lower in patients compared to HP and negatively correlated to LDL-C blood levels. No other differences were observed between the two groups apart from transferrin and ferritin concentrations. A2AR and Flotillin-1 proteins levels were positively correlated in the whole study population. Incubation of HP PBMCs with LDL-C caused a similar reduction in A2AR and Flotillin-1 expression. We suggest that LDL-C affects A2AR expression by impacting cholesterol-enriched membrane microdomains. Our results provide new insights into the molecular mechanisms underlying cholesterol toxicity, and may have important clinical implication for assessment and treatment of cardiovascular risk in HC.

Decreased skin colonization with Malassezia spp. and increased skin colonization with Candida spp. in patients with severe atopic dermatitis.

Background: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease in which patients are sensitized towards a plethora of allergens. The hosts fungal microbiota, the mycobiota, that is believed to be altered in patients suffering from AD acts as such an allergen. The correlation context of specific sensitization, changes in mycobiota and its impact on disease severity however remains poorly understood. Objectives: We aim to enhance the understanding of the specific sensitization towards the mycobiota in AD patients in relation to their fungal skin colonization. Methods: Sensitization pattern towards the Malassezia spp. and Candida albicans of 16 AD patients and 14 healthy controls (HC) were analyzed with the newly developed multiplex-assay ALEX2® and the established singleplex-assay ImmunoCAP®. We compared these findings with the fungal skin colonization analyzed by DNA sequencing of the internal transcribed spacer region 1 (ITS1). Results: Sensitization in general and towards Malassezia spp. and C. albicans is increased in AD patients compared to HC with a quantitative difference in severe AD when compared to mild to moderate AD. Further we saw an association between sensitization towards and skin colonization with Candida spp. yet a negative correlation between sensitization towards and skin colonization with Malassezia spp. Conclusion: We conclude that AD in general and severe AD in particular is associated with increased sensitization towards the hosts own mycobiota. There is positive correlation in Candida spp. skin colonization and negative in Malassezia spp. skin colonization when compared to AD, AD severity as well as to specific sensitization patterns.

Autophagy markers are decreased in bone of osteoporotic patients: a monocentric comparative study.

BACKGROUND: Osteoporosis (OP) is a pathology characterized by bone fragility affecting 30% of postmenopausal women, mainly due to estrogen deprivation and increased oxidative stress. An autophagy involvement is suspected in OP pathogenesis but a definitive proof in humans remains to be obtained. METHODS: Postmenopausal women hospitalized for femoral neck fracture (OP group) or total hip replacement (Control group) were enrolled using very strict exclusion criteria. Western blot was used to analyze autophagy level. RESULTS: The protein expression level of the autophagosome marker LC3-II was significantly decreased in bone of OP patients relative to the control group. In addition, the protein expression of the hormonally upregulated neu-associated kinase (HUNK), which is upregulated by female hormones and promotes autophagy, was also significantly reduced in bone of the OP group. CONCLUSIONS: These results demonstrate for the first time that postmenopausal OP patients have a deficit in bone autophagy level and suggest that HUNK could be the factor linking estrogen loss and autophagy decline. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03175874, 2/6/2017.