A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe.

Current approaches for the assessment of environmental and human health risks due to exposure to chemical substances have served their purpose reasonably well. Nevertheless, the systems in place for different uses of chemicals are faced with various challenges, ranging from a growing number of chemicals to changes in the types of chemicals and materials produced. This has triggered global awareness of the need for a paradigm shift, which in turn has led to the publication of new concepts for chemical risk assessment and explorations of how to translate these concepts into pragmatic approaches. As a result, next-generation risk assessment (NGRA) is generally seen as the way forward. However, incorporating new scientific insights and innovative approaches into hazard and exposure assessments in such a way that regulatory needs are adequately met has appeared to be challenging. The European Partnership for the Assessment of Risks from Chemicals (PARC) has been designed to address various challenges associated with innovating chemical risk assessment. Its overall goal is to consolidate and strengthen the European research and innovation capacity for chemical risk assessment to protect human health and the environment. With around 200 participating organisations from all over Europe, including three European agencies, and a total budget of over 400 million euro, PARC is one of the largest projects of its kind. It has a duration of seven years and is coordinated by ANSES, the French Agency for Food, Environmental and Occupational Health & Safety.

[Clinical characteristics and comorbidities associated with mortality in patients with COVID-19 in Coahuila (Mexico)]. / Características clínicas y comorbilidades asociadas a mortalidad en pacientes con COVID-19 en Coahuila (México).

Background and objective: This study aims to describe the characteristics of patients with COVID-19 in a state in northern Mexico and establish the comorbidities associated with mortality. Methods: Patients with COVID-19, divided into survivors and non-survivors, were analyzed. The data were analyzed using the chi-square test, Student's t-test, and Cox's regression model. Results: A total of 17,479 patients were included and mortality rate of 6.3% was reported. Age over 60 years (HR = 8.04; 95% CI 7.03-9.19), diabetes (HR = 1.63; 95% CI 1.40-1.89), high blood pressure (HR = 1.48; 95% CI 1.28-1.72), obesity (HR = 1.37; 95% CI 1.18-1.60) and chronic kidney disease (HR = 2.06; 95% CI 1.64-2.59) were significantly associated with mortality. Conclusions: Diabetes, high blood pressure, obesity, and chronic kidney disease increased mortality among patients with COVID-19 in the population of Coahuila, Mexico. The factor that most contributed to risk of death was age over 60 years.

Effectiveness of a decision aid for patients with knee osteoarthritis: a randomized controlled trial.

OBJECTIVE: To assess the effectiveness of a Patient Decision Aid (PtDA) for knee osteoarthritis. METHOD: Randomized controlled trial, in which 193 patients were allocated to the PtDA or usual care. Outcome measures were the Decisional Conflict Scale (DCS), knowledge of osteoarthritis and arthroplasty, satisfaction with the decision-making process (SDMP) and treatment preference, assessed immediately after the intervention. At 6 months, the same measures were applied in non-operated patients, whereas those who underwent arthroplasty completed the SDMP and the Decisional Regret Scale (DRS). RESULTS: The PtDA produced a significant immediate improvement of decisional conflict (MD = -11.65, 95%CI: -14.93, -8.37), objective knowledge (MD = 10.37, 99%IC: 3.15, 17.70) and satisfaction (MD = 6.77, 99%CI: 1.19, 12.34), and a different distribution of preferences (χ2 = 8.74, p = 0.033). Patients with less than secondary education obtained a stronger effect on decisional conflict (p = 0.015 for the interaction) but weaker for knowledge (p = 0.051). At 6 months, there were no significant differences in any variable, including the rate of total knee replacement. Operated patients showed a low level of regret, which was not affected by the intervention. CONCLUSION: The PtDA is effective immediately after its application, but it shows no effects in the medium-term. Future research should investigate which subgroups of patients could benefit more from this intervention, as well as the longitudinal evolution of decision-related psychological variables.

Diagnostic challenges in von Willebrand disease. Report of two cases with emphasis on multimeric and molecular analysis.

Identification of qualitative variants of von Willebrand disease (VWD) can be a diagnostic challenge because of discrepant results obtained in the multiple laboratory tests available for its appropriate classification. We report two cases of infrequent inherited variants of VWD with unclear preliminary results with the test panel available at the time of first consultation and that were finally diagnosed as a VWD type 2A/IID with a c.8318 G > C, p.Cys2773Ser mutation and a VWD type 2M with c.4225 T > G, p.Val1409Phe mutation, respectively. The description of these two cases highlights that despite the limited diagnostic panel for the evaluation of von Willebrand Factor (VWF) functionality, the multimeric analysis and genetic family studies were fundamental tools to achieve the final diagnosis.

End-to-end image analysis pipeline for liquid-phase electron microscopy.

Liquid phase transmission electron microscopy allows the imaging of materials in liquid environments. The sample is encapsulated within electron-beam transparent windows and hence protected by the ultrahigh vacuum necessary within the electron gun. Such an approach allows to study biological and soft materials in their natural environment and offers the possibility of accessing their dynamic nature. Yet, the electron beam scattering from the windows and solvent increases the image noise and blur. Herein, we propose a pipeline to both de-noise and sharpen images obtained by liquid transmission electron microscopy. We develop the workflow in a way that it does not require any human interference, nor introduce artefacts, but actually unveils features of the imaged samples covered by the noise and the blur. LAY DESCRIPTION: Transmission Electron Microscopy TEM is one of the most powerful techniques for structural determination at the nanoscale, with the ability to image matter down to the atomic level. TEM is only possible by keeping the electron beam under high vacuum in order to avoid undesired scattering events in the beam path. High vacuum means that the TEM samples must conventionally be in solid-state. Thus, samples in liquid form or containing liquids, like water, need special preparation techniques which tend to alter the structure and chemical nature of the sample. Such alterations are particularly critical for biological and soft organic materials where the structures are controlled by the presence of water and/or other liquids. The development of new cameras, materials and sample holders have made possible for TEM to be performed on liquid samples. Liquid Phase Transmission Electron Microscopy (LTEM) offers the possibility to investigate nanoscopic structures in liquid state and monitor dynamic processes. However important limitations come from the liquid nature of samples in the imaging process such as the low contrast afforded by organic and biological materials and additional noise and blur introduced by the liquid sample and its thickness. Existing image analysis algorithms for TEM result inadequate for LTEM. The end-to-end image analysis method herein has the ability to recover the original images together with their sharpness, without introducing any artefacts. The proposed algorithms offer the great advantage of unveiling image details which are not usually seen during imaging, thus allowing a better understanding of the nature, structure and ultimately the function of the investigated structures. The fully automatised analysis method allows to efficiently process dozens of images in few hours, improving dramatically the performance of LTEM imaging.

Evaluation of highly sensitive diagnostic tools for the detection of P. falciparum in pregnant women attending antenatal care visits in Colombia.

BACKGROUND: In low transmission settings early diagnosis is the main strategy to reduce adverse outcomes of malaria in pregnancy; however, microscopy and rapid diagnostic tests (RDTs) are inadequate for detecting low-density infections. We studied the performance of the highly sensitive-RDT (hsRDT) and the loop mediated isothermal DNA amplification (LAMP) for the detection of P. falciparum in pregnant women. METHODS: A cross-sectional study was conducted in two malaria-endemic municipalities in Colombia. We screened pregnant women in the context of an antenatal care program in health facilities and evaluated five tests (microscopy, conventional RDT, hsRDT, LAMP and nested polymerase chain reaction-PCR) for the detection of P. falciparum in peripheral blood, using a quantitative reverse transcription PCR (qRT-PCR) as the reference standard. Diagnostic performance of hsRDT and LAMP were compared with routine testing. RESULTS: The prevalence of P. falciparum was 4.5% by qRT-PCR, half of those infections were subpatent. The sensitivity of the hsRDT (64.1%) was slightly better compared to microscopy and cRDT (59 and 53.8% respectively). LAMP had the highest sensitivity (89.7%) for detecting P. falciparum and the ability to detect very low-density infections (minimum parasite density detected 0.08 p/µL). CONCLUSIONS: There is an underestimation of Plasmodium spp. infections by tests routinely used in pregnant women attending antenatal care visits. LAMP methodology can be successfully implemented at local hospitals in malaria-endemic areas. The relevance of detecting and treating this sub-patent P. falciparum infections in pregnant women should be evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03172221 , Date of registration: May 29, 2017.

Split-face study comparing conventional MAL photodynamic therapy in multiple actinic keratosis with complete time vs. half-time red light LED conventional illumination.

BACKGROUND: Conventional photodynamic therapy (PDT) with methylaminolevulinic acid (MAL) and daylight PDT have demonstrated similar efficacy in the treatment of actinic keratosis (AK). The reason for the use of daylight is to reduce pain during illumination but daylight has the limitation of the weather conditions. The difference in the doses of red light applied between these two methods suggests that an intermediate dose with red light conventional illumination could be effective in PDT of AK. OBJECTIVE: To compare the efficiency of conventional MAL-PDT with half-time conventional red light illumination in patients with multiple AK. MATERIAL AND METHODS: Adult patients with more than five symmetrically distributed AK were selected. After randomization, one area was treated with conventional PDT (Aktilite® , 630 nm, 37 J/cm2 , 8 min), while the contralateral was illuminated half time (Aktilite® , 630 nm, 37 J/cm2 , 4 min). Patients evaluated pain in each different side. Patients were evaluated at baseline, 3 and 6 months after PDT treatment by a blinded dermatologist. A questionnaire to be done at home 24 h after completing treatment was deliver to the patients to evaluate any side-effects. RESULTS: A total of 774 lesions were treated, 385 with conventional PDT and 389 with half-time PDT (P > 0.05). Conventional PDT was 85% of complete response of AK (327/385) at 3 months, and half-time PDT was 82% (319/389). At 6 months, conventional PDT was 70% (268/385) of complete response and half-time PDT was 65% (252/389). Pain during illumination was significantly lower in the VAS with the half-time protocol with a mean of 5.59 (SD 1.48) vs. 6.41 (SD 1.66) in conventional PDT. No difference in adverse effects was found between protocols. CONCLUSION: Conventional PDT with half-time illumination in multiple actinic keratosis is as effective as complete time illumination and decreased pain significantly.