Non-destructive monitoring of microalgae biofilms.

Biofilm-based cultivation systems are emerging as a promising technology for microalgae production. However, efficient and non-invasive monitoring routines are still lacking. Here, a protocol to monitor microalgae biofilms based on reflectance indices (RIs) is proposed. This framework was developed using a rotating biofilm system for astaxanthin production by cultivating Haematococcus pluvialis on cotton carriers. Biofilm traits such as biomass, astaxanthin, and chlorophyll were characterized under different light and nutrient regimes. Reflectance spectra were collected to identify the spectral bands and the RIs that correlated the most with those biofilm traits. Robust linear models built on more than 170 spectra were selected and validated on an independent dataset. Astaxanthin content could be precisely predicted over a dynamic range from 0 to 4% of dry weight, regardless of the cultivation conditions. This study demonstrates the strength of reflectance spectroscopy as a non-invasive tool to improve the operational efficiency of microalgae biofilm-based technology.

CAR-T cells for treating systemic lupus erythematosus: A promising emerging therapy.

Chimeric Antigen Receptor T-cell therapy (CAR-T), currently employed routinely for treating B-cell malignancies, has emerged as a groundbreaking approach in addressing severe autoimmune diseases, especially for systemic lupus erythematosus (SLE). The immunological rationale for targeting B lymphocytes in autoimmune diseases is well-established, demonstrating success in numerous autoantibody-mediated autoimmune conditions through targeted therapies over several years. However, this approach has often proven ineffective in the context of systemic lupus erythematosus. Recent data on CAR-T usage in lupus, revealed promising results including rapid and prolonged remission without treatment, highlighting the potential of CAR-T therapy in severe lupus cases. This article provides a comprehensive overview of CAR-T cells, tracing their evolution from hematological malignancies to their recent applications in autoimmune disorder, especially in lupus. Clinical trials within a regulated framework are now imperative to assess the procedural aspects in order to validate the considerable promise of CAR-T cell therapy in the field of autoimmune diseases. This includes evaluating safety and long-term efficacy and security of the procedure, the benefit-risk ratio in the field of autoimmunity, the availability and cost-related issues associated with this emerging cellular therapy procedure.

Does the Impact of COVID-19 on Patients With Systemic Sclerosis Change Over Time?

OBJECTIVE: The outcome of patients with COVID-19 improved over the pandemic, including patients with systemic rheumatic diseases. However, data on patients with systemic sclerosis (SSc) are lacking. This study aimed to assess the outcome of patients with both SSc and COVID-19 over several waves. METHODS: Patients with both SSc and COVID-19 who were registered in the European Scleroderma Trials and Research group (EUSTAR) were collected between April 2020 and April 2021. Patients were assigned to waves 1, 2, or 3 depending on the date of their COVID-19 diagnosis. Primary endpoints were death, intensive care unit stay, or ventilatory support (severe outcome). Subgroup analyses of patients who were hospitalized or died were conducted. General and SSc-specific characteristics and treatment were compared over the waves. Descriptive statistics and multivariate logistic regression were applied. RESULTS: A total of 333 patients were included; 57 patients (17%) had a severe outcome, and 30 patients (9%) died. Compared to wave 1, significantly fewer patients with SSc suffered from severe COVID-19 in waves 2 and 3 (28.2% vs 9.8% and 12.7%; P < 0.001), fewer patients required hospitalization (46.7% vs 19.6% and 25.5%; P < 0.001) or ventilatory support (24.0% vs 8.7% and 10.9%; P = 0.001), and fewer patients died (15.7% vs 5.0% and 7.5%; P = 0.011). Patients were significantly younger, more often men, had less frequent arterial hypertension, and less SSc cardiac involvement over waves 1 to 3. Patients received significantly less medium to high doses of corticosteroids as they did SSc treatment. CONCLUSION: The outcome of patients with both SSc and COVID-19 improved significantly over time because of intrinsic and extrinsic factors.

Normal B cells express ZAP70 in chronic lymphocytic leukemia: A link between autoimmunity and lymphoproliferation?

ZAP70 has a prognostic value in chronic lymphocytic leukemia (CLL), through altered B-cell receptor signaling, which is important in CLL pathogenesis. A good correlation between ZAP70 expression in CLL cells and the occurrence of autoimmune phenomena has been reported. Yet, the great majority of CLL-associated autoimmune cytopenia is due to polyclonal immunoglobulin (Ig) G synthesized by nonmalignant B cells, and this phenomenon is poorly understood. Here, we show, using flow cytometry, that a substantial percentage of CD5- nonmalignant B cells from CLL patients expresses ZAP70 compared with CD5- B cells from healthy subjects. This ZAP70 expression in normal B cells from CLL patients was also evidenced by the detection of ZAP70 mRNA at single-cell level with polyclonal Ig heavy- and light-chain gene transcripts. ZAP70+ normal B cells belong to various B-cell subsets and their presence in the naïve B-cell subset suggests that ZAP70 expression may occur during early B-cell development in CLL patients and potentially before malignant transformation. The presence of ZAP70+ normal B cells is associated with autoimmune cytopenia in CLL patients in our cohort of patients, and recombinant antibodies produced from these ZAP70+ nonmalignant B cells were frequently autoreactive including anti-platelet reactivity. These results provide a better understanding of the implication of ZAP70 in CLL leukemogenesis and the mechanisms of autoimmune complications of CLL.

Exploring the dynamics of astaxanthin production in Haematococcus pluvialis biofilms using a rotating biofilm-based system.

Microalgae biofilm emerged as a solid alternative to conventional suspended cultures which present high operative costs and complex harvesting processes. Among several designs, rotating biofilm-based systems stand out for their scalability, although their primary applications have been in wastewater treatment and aquaculture. In this work, a rotating system was utilized to produce a high-value compound (astaxanthin) using Haematococcus pluvialis biofilms. The effect of nitrogen regime, light intensity, and light history on biofilm traits was assessed to better understand how to efficiently operate the system. Our results show that H. pluvialis biofilms follow the classical growth stages described for bacterial biofilms (from adhesion to maturation) and that a two-stage (green and red stages) allowed to reach astaxanthin productivities of 204 mg m-2 d-1 . The higher light intensity applied during the red stage (400 and 800 µmol m-2 s-1 ) combined with nitrogen depletion stimulated similar astaxanthin productivities. However, by training the biofilms during the green stage, using mild-light intensity (200 µmol m-2 s-1 ), a process known as priming, the final astaxanthin productivity was enhanced by 40% with respect to biofilms pre-exposed to 50 µmol m-2 s-1 . Overall, this study shows the possibility of utilizing rotating microalgae biofilms to produce high-value compounds laying the foundation for further biotechnological applications of these emerging systems.

Health related quality of life, remission and low lupus disease activity state in patients with systemic lupus erythematosus.

OBJECTIVES: To measure the association between systemic lupus erythematosus (SLE) remission and scores of patients reported outcome measures (PRO). METHODS: We performed a prospective cohort study of SLE patients with a 2-year follow-up, recording LupusPRO, LupusQol, SLEQOL, and SF-36 questionnaires. Remission was defined as remission-off-treatment (ROFT) and remission-on-treatment (RONT) according to the DORIS consensus. Mixed models accounting for repeated measures were used to compare groups as follow: ROFT and RONT versus no remission, and Lupus Low Disease activity state (LLDAS) versus no LLDAS. RESULTS: A total of 1478 medical visits and 2547 PRO questionnaires were collected during the follow-up from the 336 recruited patients. A between-group difference in PRO scores reaching at least 5 points on a 0-100 scale was obtained in the following domains: "lupus symptoms" (LLDAS: +5 points on the 0-100 scale, RONT: +9 and ROFT: +5), "lupus medication" (LLDAS: +5, RONT: +8 and ROFT: +9), "pain vitality" (LLDAS: +6, RONT: +9 and ROFT: +6) of LupusPRO, "role emotional" (LLDAS: +5, RONT: +8), "role physical" (RONT: +7 and ROFT: +7), "bodily pain" (RONT: +6), "mental health" (RONT: +5) and "social functioning" (RONT: +6) of SF-36. In contrast, a between-group difference reaching at least 5 points was not achieved for any of the LupusQol and SLEQOL domains. CONCLUSIONS: RONT, ROFT, and LLDAS were associated with significant and clinically relevant higher quality of life in most PRO domains of LupusPRO (disease-specific) and SF-36 (generic) questionnaires, but not with LupusQol and SLEQOL disease-specific questionnaires.

Bragg coherent diffraction imaging with the CITIUS charge-integrating detector.

The CITIUS detector is a next-generation high-speed X-ray imaging detector. It has integrating-type pixels and is designed to show a consistent linear response at a frame rate of 17.4 kHz, which results in a saturation count rate of over 30 Mcps pixel-1 when operating at an acquisition duty cycle close to 100%, and up to 20 times higher with special extended acquisition modes. Here, its application for Bragg coherent diffraction imaging is demonstrated by taking advantage of the fourth-generation Extremely Brilliant Source of the European Synchrotron (ESRF-EBS, Grenoble, France). The CITIUS detector outperformed a photon-counting detector, similar spatial resolution being achieved (20 ±â€…6 nm versus 22 ±â€…9 nm) with greatly reduced acquisition times (23 s versus 200 s). It is also shown how the CITIUS detector can be expected to perform during dynamic Bragg coherent diffraction imaging measurements. Finally, the current limitations of the CITIUS detector and further optimizations for coherent imaging techniques are discussed.

Influence of systemic sclerosis on periodontal health: A case-control study.

AIM: Patients with systemic sclerosis (SSc) present various clinical and radiological oral manifestations. However, precise evaluation of the oral features associated with diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) is limited. The objective of this study was to evaluate the periodontal ligament (PDL) surface in SSc patients in comparison with controls. Assessment of oral-health-related quality of life (OHRQoL) and the levels of different biomarkers in the gingival crevicular fluid (GCF) was performed. MATERIALS AND METHODS: SSc patients and matched controls underwent standardized oral examination and cone-beam computed tomography (CBCT). Levels of interleukin-6 (IL-6), chemokine (C-X-C motif) ligand 4 (CXCL-4) and matrix metalloproteinase-9 (MMP-9) in the GCF were determined by enzyme-linked immunosorbent assay. PDL surface was measured on CBCT axial views. OHRQoL was quantified using the Mouth Handicap in SSc Scale (MHISS). RESULTS: Thirty-nine SSc patients and 39 controls were included. SSc patients exhibited increased PDL surface, higher number of missing teeth as well as elevated IL-6, MMP-9 and CXCL-4 levels. Reduced mouth opening was observed in dcSSc but not in lcSSc patients. MHISS score was higher in dcSSc than in lcSSc patients. Although worse periodontal parameters were found in both subgroups compared with controls, dcSSc patients presented lower gingival inflammation. CONCLUSIONS: SSc is associated with PDL space widening, impaired oral health and OHRQoL.

Santé sexuelle et discriminations croisées chez les hommes afro-latino-caribéens ayant des rapports sexuels avec des hommes à Bruxelles.

INTRODUCTION: The starting point of our article is the observation that the target group of Afro-Latin-Caribbean men, who have sex with men, is not reached by sexual health promotion programs for MSM, nor by those aimed at Afro-Latino-Caribbean audiences. Indeed, it seems to be in a blind spot of prevention programs designed by key audiences. PURPOSE OF RESEARCH: The objective of our article is to understand the vulnerabilities of this group, the impacts of its invisibility and the intersectoral discrimination (homophobia, racism, …) of which itis victim on the management of his sexual health, in order to highlight ways to improve prevention programs towards this group. RESULTS: Our study highlighted some vulnerabilities inherent in being Afro-Latino-Caribbean MSM and the impact of the intersectional discrimination on the management of their sexual health. We have also demonstrated the invisibility suffered by these audiences and their request to be recognized in their specificities, particularly through the creation of secure places that would be entirely dedicated to them. CONCLUSIONS: This project allowed us to highlight the importance, for minority audiences, of being visibilized and to have their specificities recognized in sexual health promotion programs. This is even more important when they are victims of multiple discrimination. It also showed the importance of implementing actions that promote the empowerment of vulnerable audiences.

Refining Incidence and Characteristics of Inflammatory Myopathies: A Quadruple-Source Capture-Recapture Survey Using the 2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria.

OBJECTIVE: Inflammatory myopathies (IM), characterized by muscle inflammation and weakness, are rare systemic diseases. Our previous study estimated an IM incidence rate of 7.98 cases per million people per year (95% confidence interval 7.38-8.66) and highlighted important variations that were likely because of methodologic issues rather than true epidemiologic differences. In this study, we aimed to refine the incidence of IM, using the 2017 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for IM and a quadruple-source capture-recapture method during a 6-year period in Alsace, France, a region with a population of 2 million having benefits of good access to health care and accredited IM referral centers. METHODS: Clinical data of potential IM patients were obtained from 4 sources (general practitioners and community specialists, public and private hospital records, public and private laboratories, and archives from the pathology department). Patients residing in Alsace and who fulfilled the 2017 EULAR/ACR criteria for IM between January 1, 2006, and January 1, 2013, were included. We corrected potentially incomplete ascertainment of cases with capture-recapture analyses. We studied both spatial and temporal distributions of incidence of IM. We also assessed systemic manifestations of the disease. RESULTS: Our review of 1,742 potential cases identified 106 patients with IM. No spatial or temporal heterogeneity was observed. Use of log-linear models showed an estimated 14.9 additional missed cases. Thus, the incidence rate of IM was 8.22 new cases per million inhabitants per year (95% confidence interval 6.76-9.69). Extramuscular manifestations other than dermatomyositis rash were frequently recorded. CONCLUSION: The stringent methodology used in our study provides an accurate estimation of the incidence of IM. This study also demonstrates, in a population-based cohort, the systemic nature of IM.

French guidelines for the etiological workup of eosinophilia and the management of hypereosinophilic syndromes.

Eosinophilic-related clinical manifestations are protean and the underlying conditions underpinning eosinophilia are highly diverse. The etiological workup of unexplained eosinophilia/hypereosinophilia can be challenging, and can lead sometimes to extensive, inappropriate, costly and/or invasive investigations. To date, guidelines for the etiological workup and management of eosinophilia are mainly issued by hematologists, and thus mostly cover the scope of clonal hypereosinophilic syndromes (HES). Here, thanks to an extensive literature review, and thanks to the joint work of a large panel of experts involving physicians from both adult and pediatric medicine and from various subspecialties (as well as a representative of a patients' association representative), we provide recommendations for both the step-by step diagnostic workup of eosinophilia (whether unexplained or within specific contexts) as well as the management and follow-up of the full spectrum of eosinophilic disorders (including clonal, reactive, lymphocytic and idiopathic HES, as well as single-organ diseases). Didactic prescription summaries intended to facilitate the prescription of eosinophil-targeted drugs are also provided, as are practical diagnostic and therapeutic algorithms. Lastly, this set of recommendations also includes a summary intended for general practitioners, as well as an overview of the therapeutic patient education program set up by the French reference center for HES. Further updates will be mandatory as new validated information emerges.

The mediating effect of fatigue in impaired quality of life in systemic lupus erythematosus: mediation analysis of the French EQUAL cohort.

OBJECTIVES: Mediation analyses were conducted to measure the extent to which musculoskeletal (MSK) flares and depression affected physical health through excessive fatigue. METHODS: Mediation analyses were performed in a large multicentre cohort of SLE patients. Domains of the LupusQoL and SLEQOL questionnaires were selected as outcomes, MSK flares according to the SELENA-SLEDAI flare index (SFI-R) score and depression defined by Center for Epidemiologic Studies-Depression scale (CES-D) scale as exposures and different fatigue domains from MFI-20 and LupusQoL questionnaires as mediators. For each model, total, direct, indirect effects and proportion of effect mediated by fatigue (i.e. proportion of change in health-related quality of life) were determined. RESULTS: Of the 336 patients, 94 (28%) had MSK flares at inclusion and 99 (29.5%) were considered with depression. The proportion of the total effect of MSK flares on physical health impairment explained by fatigue ranged from 59.6% to 78% using the LupusQOL 'Physical health' domain and from 51.1% to 73.7% using the SLEQOL 'Physical functioning' domain, depending on the fatigue domain selected. The proportion of the total effect of depression on physical health impairment explained by fatigue ranged from 68.8% to 87.6% using the LupusQOL 'Physical health' domain and from 79.3% to 103.2% using the SLEQOL 'Physical functioning' domain, depending on the fatigue domain selected. CONCLUSIONS: The effect of MSK flares and depression on physical health impairment is largely mediated by fatigue. Thus, the patient's perception of disease activity as measured by physical health is largely influenced by fatigue. In addition, fatigue has a significant negative impact on quality of lifeof SLE patients with depression. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904812.

Impact of COVID-19 on the Belgian HIV epidemic: slowdown of HIV transmission and testing and adaptation of care.

BACKGROUND: To gain insight into the impact of the COVID-19 pandemic and containment measures on the HIV epidemic and services, this study aims to describe HIV trends in 2020 and compare them with previous years. METHODS: Belgian national HIV surveillance data 2017-2020 were analysed for trends in HIV testing, HIV diagnoses, VL measurements, ART uptake and PrEP purchase. Descriptive statistics from 2020 are compared to annual averages from 2017 to 2019 (proportional difference, %). RESULTS: In 2020, 725 HIV infections were diagnosed in Belgium (- 21.5% compared to 2019). The decline was most pronounced during the first lockdown in April-May but also present in July-December. The number of HIV tests performed decreased by 17.6% in 2020, particularly in March-May and October-December (- 57.5% in April and -25.4% in November 2020 compared to monthly 2017-19 numbers). Diagnosis of acute HIV infections decreased by 47.1% in 2020 (n = 27) compared to 2019 (n = 51). Late HIV diagnoses decreased by 24.7% (95% CI [- 40.7%; -9.7%]) in 2020 compared to 2019. Of patients in care in 2019, 11.8% interrupted HIV care in 2020 compared to 9.1% yearly in the 3 previous years. The number of HIV patients with VL monitoring per month dropped in March-May 2020, whilst proportions of VL suppression and ART coverage remained above 86% and 98.5% respectively in 2020. PrEP purchases, number of purchasers and starters dropped during April-May 2020 (respectively - 45.7%, - 47.4%, - 77.9% in April compared to February 2020). CONCLUSIONS: The significant decrease in HIV diagnoses in Belgium in 2020 coincided with the COVID-19 pandemic and following containment measures, particularly in April-May during the first lockdown. A slowdown of HIV transmission due to reduced HIV risk exposure is suggested by the halving in diagnosis of acute HIV infections in March-December 2020 compared to the previous year, and the adaptive decrease in PrEP use and PrEP initiation from April onwards. Despite a slight increase in HIV care interruptions, the indicators of quality of HIV care remained stable. Access to prevention, testing and care for all people living with HIV and at risk of acquiring HIV is a priority during and after times of pandemic.

Fatigue is independently associated with disease activity assessed using the Physician Global Assessment but not the SLEDAI in patients with systemic lupus erythematosus.

OBJECTIVES: To analyse whether reported fatigue, one of the most challenging manifestations of systemic lupus erythematosus (SLE), may bias the assessment of disease activity in SLE according to the Physician Global Assessment (PGA). METHODS: Patients from the Lupus BioBank of the upper Rhein database, a cross-sectional multicentre collection of detailed clinical and biological data from patients with SLE, were included. Patients had to fulfil the 1997 American College of Rheumatology criteria for SLE and the PGA (0-3 scale) at the time of inclusion had to be available. Fatigue was assessed according to the Fatigue Scale for Motor and Cognitive Functions. Univariate and multivariate regression models were built to determine which variables were associated with the PGA. RESULTS: A total of 350 patients (89% female; median age: 42 years, IQR: 34-52) were included. The median Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 4 (IQR: 2-6). Of these 350 patients, 257 (73%) reported significant fatigue. The PGA (p=0.004) but not the SELENA-SLEDAI (p=0.43) was significantly associated with fatigue. Both fatigue and SELENA-SLEDAI were independently associated with the PGA in two different multivariate models. CONCLUSION: Fatigue is independently associated with disease activity assessed using the PGA but not the SLEDAI. These findings highlight the fact that the PGA should capture only objectively active disease manifestations in order to improve its reliability.

Electronic, non-linear optical, optoelectronic, and thermodynamic properties of undoped and doped bis (ethylenedithio) tetraselenafulvalene (BETS) (C10H8S4Se4) molecule: first study using ab initio investigation.

We have performed the ab initio calculation of the undoped and doped molecules bis (ethylenedithio) tetraselenafulvalene (BETS). Carbone (C) atoms have been substituted by Boron (B) to investigate their effects on the electronic structure and nonlinear optical, optoelectronic, and thermodynamic properties of BETS molecule. The RHF and hybrid density functional theories (WB97XD, B3PW91, and B3LYP) methods were applied, using the cc-pVDZ basis set. We found that the energy gap (Egap) of the doped molecules are respectively 2.476 eV and 2.569 eV for C8B2H8S4Se4 and C7B3H8S4Se4 with B3LYP/cc-pVDZ basis set, lower than one of the undoped molecule (3.316 eV). The significant increase values of polarizability (˂α˃) and first order hyperpolarizability (ß) of the doped compounds, especially in C8B2H8S4Se4 (< α > = 4.5315 × 10-23 esu, ß = 22,672.27 × 10-33 esu and < α > = 4.518 × 10-23 esu, ß = 23,657.43 × 10-33 esu respectively for B3LYP and B3PW91) compared to those of the undoped molecule (< α > = 4.3602 × 10-23 esu, ß = 1290.38 × 10-33 esu, and < α > = 4.518 × 10-23 esu) show that the new molecules have a good nonlinear optical property. Results suggest that these molecules doped with boron are a potential candidate as semiconductors compounds and nonlinear optical materials.

The architecture and metabolic traits of monospecific photosynthetic biofilms studied in a custom flow-through system.

Microalgae biofilms have great ecological importance and high biotechnological potential. Nevertheless, an in-depth and combined structural (i.e., the architecture of the biofilm) and physiological characterization of microalgae biofilms is still missing. An approach able to provide the same time physiological and structural information during biofilm growth would be of paramount importance to understand these complex biological systems and to optimize their productivity. In this study, monospecific biofilms of a diatom and a green alga were grown under dynamic conditions in custom flow cells represented by UV/Vis spectroscopic cuvettes. Such flow cells were conceived to characterize the biofilms by several techniques mostly in situ and in a nondestructive way. Physiological traits were obtained by measuring variable chlorophyll a fluorescence by pulse amplitude modulated fluorometry and by scanning the biofilms in a spectrometer to obtain in vivo pigments spectral signatures. The architectural features were obtained by imaging the biofilms with a confocal laser scanning microscopy and an optical coherence tomography. Overall, this experimental setup allowed us to follow the growth of two biofilm-forming microalgae showing that cell physiology is more affected in complex biofilms likely as a consequence of alterations in local environmental conditions.

Improving patient pathways for systemic lupus erythematosus: a multistakeholder pathway optimisation study.

OBJECTIVE: Among the most significant challenges in SLE are the excessive diagnosis delay and the lack of coordinated care. The aim of the study was to investigate patient pathways in SLE in order to improve clinical and organisational challenges in the management of those with suspected and confirmed SLE. METHODS: We conducted a cross-sectional study of patients with SLE, healthcare providers and other representative stakeholders. Focus groups were conducted, and based on the collected data the most impactful disruption points in SLE patient pathways were identified. A novel framework to improve individual patient pathways in SLE was developed, discussed and validated during a consensus meeting with representative stakeholders. RESULTS: Six thematic clusters regarding disruption in optimal patient pathways in SLE were identified: appropriate and timely referral strategy for SLE diagnosis; the need for a dedicated consultation during which the diagnosis of SLE would be announced, and following which clarifications and psychological support offered; individualised patient pathways with coordinated care based on organ involvement, disease severity and patient preference; improved therapeutic patient education; prevention of complications such as infections, osteoporosis and cancer; and additional patient support. During the consensus meeting, the broader panel of stakeholders achieved consensus on these attributes and a framework for optimising SLE patient pathways was developed. CONCLUSIONS: We have identified significant disruption points and developed a novel conceptual framework to improve individual patient pathways in SLE. These data may be of valuable interest to patients with SLE, their physicians, health organisations as well as policy makers.

Health-related quality of life in patients with mixed connective tissue disease: a comparison with matched systemic sclerosis patients.

OBJECTIVES: Health-Related Quality of Life (HRQoL) in adult patients with mixed connective tissue disease (MCTD) has not been described so far. Therefore, we performed an explorative study to evaluate HRQoL in MCTD patients. METHODS: MCTD patients fulfilling the Kahn criteria and participating in the prospective follow-up cohort for MCTD of the Leiden University Medical Center were included; and matched to systemic sclerosis (SSc) patients based on age, sex and disease duration. Data on disease characteristics and HRQoL (SF36 and EQ-5D) were collected annually. HRQoL was compared between MCTD and SSc patients at baseline. Factors associated with HRQoL in MCTD were identified using linear regression and change in HRQoL over 3 years using linear mixed models. RESULTS: Thirty-four MCTD patients (121 visits) and 102 SSc patients (424 visits) were included. At baseline, MCTD patients presented with interstitial lung disease, cardiac involvement, synovitis and myositis more frequently compared to SSc patients, while use of immunosuppressive medication was less frequent. In both groups, mean SF36 scores were lower than in the general Dutch population. The SF36 subscore "general health perception" was impacted most in both groups (MCTD: 38.5 [SD:7.0], SSc: 39.9 [SD:8.9]). During follow-up, SF36 scores improved in MCTD patients, while EQ5DNL remained stable. No specific characteristics were identified that associated with baseline HRQoL or change in HRQol over time. CONCLUSIONS: Like in SSc, HRQoL in MCTD is significantly impaired, especially the general health perception of patients. Evaluation in larger prospective cohorts is needed to identify characteristics that impact HRQol most.

Toxicological analysis of a "poison vial" found in the remains of an SS soldier (Maltot, Normandy, France).

In Maltot (Normandy, France), one grave containing the remains of a German soldier, who died in 1944, was excavated amongst other graves and isolated elements. A dozen whole vials were unearthed, resulting in questions about their content. Various screenings were carried out on the contents of one single vial: HPLC-DAD and HR-LC-MS screening after 1/10 dilution in mobile phase, GC-MS and HS-GC-MS after 1/10 dilution in methanol, multi-element research by HR-ICP-MS after total mineralization, and cyanide analysis. Analyzed vial contained approximately 300 µL of a colorless, water-immiscible liquid with a characteristic solvent odor. HPLC-DAD, GC-MS, HR-LC-MS/MS, ICP-MS, and cyanide screenings were negative excluding the presence of cyanide, arsenic, barbiturates, amphetamines, or narcotics. HS-GC-MS analysis highlighted the presence of ethanol, chloroform, and diethyl ether at significant concentrations. Chloroform and diethyl ether were anesthetic products mainly reserved for urgent situations. We hypothesized that the soldier may have been a combat medic working on battlefields. as he was wounded, another possibility could be that he may have used the vials to relieve his pain; however, the immediate severity of the wounds drove us to assess the second hypothesis of delayed death as being less plausible. The high number of vials containing ethanol, chloroform, and diethyl ether, and the massive blood loss leading to quick death led us to support the combat medic or paramedic hypothesis.