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Introduction: Methotrexate (MTX) is a folate antagonist used as an immunosuppressant in a number of conditions, including rheumatoid arthritis (RA). Low-dose MTX (MTX-LD) is associated with a risk of haematological, hepatic, gastrointestinal and pulmonary toxicity, which may up until now have limited its use., State of the Art: In RA, data from retrospective cohorts have reported a possible excess risk of methotrexate toxicity in cases of underlying interstitial lung disease (ILD). However, recent prospective and retrospective multicentre studies have found no such increased risk, and have reassuringly concluded that MTX-LD can be prescribed in cases of RA-associated ILD (RA-ILD)., Perspectives and Conclusions: Current recommendations are not to delay the introduction of MTX in patients with RA at risk of developing ILD or in the presence of RA-ILD with mild to moderate respiratory impairment., (Copyright © 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Although electronic consults (e-consults) are utilized in healthcare systems by medical professionals, use of e-consults by pharmacy remains novel outside of niche disease states. Additional research is required to fill literature gaps to assist in optimizing the pharmacist's role in e-consult programs. Objective: This study aimed to assess the impact of pharmacist expertise on e-consult outcomes. Methods: This study was a retrospective review of all pharmacy e-consults completed by pharmacists at a large academic health system between March 1st, 2020, and August 31st, 2022. This was deemed quality improvement and did not require Institutional Review Board approval. E-consults were identified using a report. Key data collection points included e-consult disease state, ordering provider, pharmacists' specialty, and recommendation result. The primary outcome was the difference in acceptance rates of expert versus non-expert pharmacist recommendations. Secondary outcomes included the overall implementation rate, implementation rate over time, acceptance rate between provider types, time to implementation, and pharmacist response time. Acceptance rates were compared between expert/non-expert dichotomy via Pearson chi-square test. Results: A total of 375 e-consults met inclusion criteria and spanned 19 unique disease states. The three most common included diabetes mellitus (27.0%), pain management (13.1%), and mental health (11.0%). Nearly 60% of e-consults were in a disease with an expert. The provider acceptance rate was higher when e-consults were completed by an expert versus non-expert (62.6% versus 39.6% respectively, p = 0.002). The overall implementation rate was 51.8%. Physicians (MD/DOs) accepted the pharmacist's recommendations 55.6% of the time, advanced practice registered nurses (APRNs) 64.7%, physician assistants (PAs) 100.0%, and other professionals 25.0% (p = 0.033). Mean time to recommendation implementation was 16.5 days (SD = 29.4 days). Mean time to pharmacist response was 1.1 days (SD = 1.4 days). Conclusions: Comprehensive e-consult programs are more successful when integrating expert pharmacists., (© Individual authors.)

Background: The safety and efficacy of botulinum neurotoxin type A (BoNTA) treatments are well established, but injection techniques, target muscles, and toxin doses continue to evolve, with each refinement producing improvements in treatment outcomes. The recommendations in this consensus move away from standard templates and illustrate how to tailor treatments to individual patterns and strengths of muscle activity, and patient preferences., Methods: Seventeen experts in the fields of plastic surgery, dermatology, ophthalmology, otorhinolaryngology, and neurology convened in 2022 to develop consensus-based recommendations for the use of botulinum toxin A for the treatment of horizontal forehead lines, glabellar frown lines, and crow's feet lines that reflect current clinical practice. The focus was on how to tailor injections to individual patients to optimize treatment outcomes., Results: For each upper face indication, consensus members describe how to perform a dynamic assessment to optimize the dose and injection technique for each patient. A tailored treatment protocol is presented for commonly observed patterns of dynamic lines. Units of Inco are defined and the precise location of injection points, illustrated with the use of anatomical images., Conclusion: This consensus provides up-to-date recommendations on the tailored treatment of upper facial lines based on the latest research and collective clinical experience of the expert injectors. Optimal outcomes require thorough patient evaluation, both at rest and during animation, using both visual and tactile cues; detailed understanding of facial muscular anatomy and how opposing muscles interact; and use of a BoNTA with high precision to target identified zones of excess muscle activity., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Perceived burdensomeness (PB), defined by an intractable perception of burdening others, often reflects a false mental calculation that one's death is worth more than one's life and has been supported as a significant risk factor for suicide. Because PB often reflects a distorted cognition, it may serve as a corrective and promising target for the intervention of suicide. More work on PB is needed in clinically severe and in military populations. Sixty-nine (Study 1) and 181 (Study 2) military participants at high baseline suicide risk engaged in interventions targeting constructs relating to PB. Baseline and follow-up measures (at 1, 6, 12, 18, and 24 months) of suicidal ideation were administered, and various statistical approaches-including repeated-measures ANOVA, mediation analyses, and correlating standardized residuals-explored whether suicidal ideation decreased specifically by way of PB. In addition to utilizing a larger sample size, Study 2 included an active PB-intervention arm (N = 181) and a control arm (N = 121), who received robust care as usual. In both studies, participants improved considerably regarding baseline to follow-up suicidal ideation. The results of Study 2 mirrored those of Study 1, corroborating a potential mediational role for PB in treatment-related improvements in suicidal ideation in military participants. Effect sizes ranged from .07-.25. Interventions tailored at decreasing levels of perceived burdensomeness may be uniquely and significantly effective in reducing suicidal thoughts., (Copyright © 2023 Association for Behavioral and Cognitive Therapies. Published by Elsevier Ltd. All rights reserved.)

The ability to monitor one's behaviour is frequently impaired following TBI, impacting on patients' rehabilitation. Inaccuracies in judgement or self-reflection of one's performance provides a useful marker of metacognition. However, metacognition is rarely measured during routine neuropsychology assessments and how it varies across cognitive domains is unclear. A cohort of participants consisting of 111 TBI patients [mean age = 45.32(14.15), female = 29] and 84 controls [mean age = 31.51(12.27), female = 43] was studied. Participants completed cognitive assessments via a bespoke digital platform on their smartphones. Included in the assessment were a prospective evaluation of memory and attention, and retrospective confidence judgements of task performance. Metacognitive accuracy was calculated from the difference between confidence judgement of task performance and actual performance. Prospective judgment of attention and memory was correlated with task performance in these domains for controls but not patients. TBI patients had lower task performance in processing speed, executive functioning and working memory compared to controls, maintaining high confidence, resulting in overestimation of cognitive performance compared to controls. Additional judgments of task performance complement neuropsychological assessments with little additional time-cost. These results have important theoretical and practical implications for evaluation of metacognitive impairment in TBI patients and neurorehabilitation.

The European Initiative HBM4EU aimed to further establish human biomonitoring across Europe as an important tool for determining population exposure to chemicals and as part of health-related risk assessments, thus making it applicable for policy advice. Not only should analytical methods and survey design be harmonized and quality assured, but also the evaluation of human biomonitoring data. For the health-related interpretation of the data within HBM4EU, a strategy for deriving health-based human biomonitoring guidance values (HBM-GVs) for both the general population and workers was agreed on. On this basis, HBM-GVs for exposure biomarkers of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), phthalates (diethyl hexyl phthalate (DEHP), di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), butyl benzyl phthalate (BBzP), and bis-(2-propylheptyl) phthalate (DPHP)), bisphenols A and S, pyrethroids (deltamethrin and cyfluthrin), solvents (1-methyl-2-pyrrolidone (NMP), 1-ethylpyrrolidin-2-one (NEP), N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC)), the heavy metal cadmium and the mycotoxin deoxynivalenol (DON) were developed and assigned a level of confidence. The approach to HBM-GV derivations, results, and limitations in data interpretation with special focus on the pyrethroids are presented in this paper., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Purpose: The purpose of this study was to determine the frequency of detection of isthmoceles by ultrasound 6 months after caesarean section (CS) and which symptoms associated with isthmocele formation occur after CS. Subsequently, it was determined how often the ultrasound finding "isthmocele" coincided with the presence of complaints., Methods: A prospective multicentre cohort study was conducted with 546 patients from four obstetric centres in Berlin, who gave birth by primary or secondary CS from October 2019 to June 2020. 461 participants were questioned on symptoms 3 months after CS; 329 participants were included in the final follow-up 6 months after CS. The presence of isthmoceles was determined by transvaginal sonography (TVS) 6 months after CS, while symptoms were identified by questionnaire., Results: Of the 329 women, 146 (44.4%) displayed an isthmocele in the TVS. There was no statistically significant difference in the manifestation of symptoms between the two groups of women with and without isthmocele; however, when expressed on a scale from 1 to 10 the intensity of both scar pain and lower abdominal pain was significantly higher in the set of women that had shown to have developed an isthmocele (p = 0.014 and p = 0.031, respectively)., Conclusion: The prevalence of isthmoceles 6 months after CS was 44.4%. Additionally, scar pain and lower abdominal pain were more pronounced when an isthmocele was also observed in the TVS., Trial Registration: Trial registration number DRKS00024977. Date of registration 17.06.2021, retrospectively registered., (© 2022. The Author(s).)

Quantum cascade detectors (QCDs) are devices operating at zero external bias with a low dark-current. They show linear detection and high saturation intensities, making them suitable candidates for heterodyne detection in long-wave infrared (LWIR) free space optical communication systems. We present an approach to mitigate the performance limitation at long wavelengths, by a comparison of similar single and multi-period QCDs for optimizing their responsivity and noise behaviour. Our InGaAs/InAlAs/InP ridge QCDs are designed for operation at λ = 9.124 µm. Optical waveguide simulations support the accurate optical characterization. A detailed device analysis reveals room-temperature responsivities of 111 mA/W for the 15-period and 411 mA/W for the single-period device.

The last several decades have witnessed growing and converging evidence from randomized controlled trials (RCT's) that an identifiable set of simple clinical management strategies are effective for those at risk for suicidal thinking and/or suicide attempts. The current article offers a brief review of clinical strategies supported by RCT's targeting suicidality as "commonalities of treatments that work" and related recommendations for use in the delivery of care for suicidal individuals in generic fashion, regardless of any particular treatment, theoretical orientation, or intervention perspective. The article includes eight recommendations that can be easily adapted across the full range of clinical contexts, institutional settings, and delivery systems, recommendations that help frame a broader clinical narrative for suicide prevention. Recommendations cut across five identifiable domains or clinical strategies for the delivery of care: (1) informed consent discussion that identifies risks of opting out of care and emphasizes the importance of shared responsibility and a collaborative process, (2) an explanatory model that emphasizes the importance of individual self-management skills and targeting the causes of suicide rather than describing suicidality as a function of mental illness, (3) the importance of proactively identifying barriers to care and engaging in targeted problem-solving to facilitate treatment adherence, (4) a proactive and specific plan for management of future suicidal episodes, and (5) reinforcing the importance of taking steps to safeguard lethal means and facilitate safe storage of firearms., Competing Interests: DJ is an owner in CAMS-care. MD and SF own an interest in Oui Therapeutics. CB serves as a consultant for Oui Therapeutics. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 David Rudd, Bryan, Jobes, Feuerstein and Conley.)

Trapeziometacarpal (TM) Osteoarthritis is one of the most common osteoarthritis. It causes pain, loss of mobility and strength and affected function in daily life. Splint is one of the conservative treatments proposed to patients. The purpose of this study was to assess the effect of this conservative treatment on pain, function and quality of life at long-term. We sent 193 questionnaires to patients who received a CMC splint for their TM osteoarthritis. The CMC splint immobilizes only the TM joint and leaves free the interphalangeal joint of the thumb and the wrist. First, we comptuted how many patients had finally undergone surgical treatment. On the non-operated patients, we analyzed the pain (VAS), the function (QuickDASH score) and the quality of life (SF-12). We compared the results to literature and norms. Finally, 186 people could be included in the study ,115 we answered and 28 were operated on (24%). After 4 years (3.8±1.7 yrs) of conservative treatment, The VAS and QuickDASH scores were significantly worse comparatively to a cohort of healthy patients, trapezectomy and arthrodesis patients. The SF-12 scores were reduced from 20% comparative to norms. In conclusion, few patients had surgery after splinting as a conservative treatment. However, these non- operated patients do not provide good results.

The impact of immune system and inflammation on organ homeostasis and tissue stem cell niches in the absence of pathogen invasion has long remained a conundrum in the field of regenerative medicine. The paradoxical role of immune components in promoting tissue injury as well as resolving tissue damage has complicated therapeutic targeting of inflammation as a means to attain tissue homeostasis in degenerative disease contexts. This confound could be resolved by an integrated intricate assessment of cross-talk between inflammatory components and micro- and macro-environmental factors existing in tissues during health and disease. Prudent fate choice decisions of stem cells and their differentiated progeny are key to maintain tissue integrity and function. Stem cells have to exercise this fate choice in consultation with other tissue components. With this respect tissue immune components, danger/damage sensing molecules driving sterile inflammatory signaling cascades and barrier cells having immune-surveillance functions play pivotal roles in supervising stem cell decisions in their niches. Stem cells learn from their previous damage encounters, either endogenous or exogenous, or adapt to persistent micro-environmental changes to orchestrate their decisions. Thus understanding the communication networks between stem cells and immune system components is essential to comprehend stem cell decisions in endogenous tissue niches. Further the systemic interactions between tissue niches integrated through immune networks serve as patrolling systems to establish communication links and orchestrate micro-immune ecologies to better organismal response to injury and promote regeneration. Understanding these communication links is key to devise immune-centric regenerative therapies. Thus the present review is an integrated attempt to provide a unified purview of how inflammation and immune cells provide guidance to stem cells for tissue sculpting during development, organismal aging and tissue crisis based on the current knowledge in the field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garg, Chandanala, David-Luther, Govind, Prasad, Kumar and Prasanna.)

Background: College students are a priority population for health insurance literacy interventions. Yet, there are few psychometric studies on measuring health insurance knowledge - a core construct of health insurance literacy., Methods: We administered a health insurance survey to 2,250 college students. We applied Classical Test Theory and Item Response Theory methods to estimate psychometric properties of the Kaiser Family Foundation's 10-item health insurance knowledge quiz., Results: The scale is unidimensional, and a two-parameter logistic model best fit the data. IRT estimates indicated varying item discriminations ( a range: 0.717-2.578) and difficulties ( b range: -0.913-1.790). Precision of measurement was maximized for students half a standard deviation below the mean (θ = -0.686) health insurance knowledge ability., Conclusions: This scale can be used to identify gaps in health insurance knowledge among college students and be applied in clinical and community health education practice., (© Copyright 2021 Springer Publishing Company, LLC.)

Background: An effective cross-cultural doctor-patient communication is vital for health literacy and patient compliance. Building a good relationship with medical staff is also relevant for the treatment decision-making process for cancer patients. Studies about the role of a specific migrant background regarding patient preferences and expectations are lacking. We therefore conducted a multicentre prospective survey to explore the needs and preferences of patients with a migrant background (PMB) suffering from gynecological malignancies and breast cancer to evaluate the quality of doctor-patient communication and cancer management compared to non-migrants (NM)., Methods: This multicentre survey recruited patients with primary or recurrence of breast, ovarian, peritoneal, or fallopian tube cancer. The patients either filled out a paper form, participated via an online survey, or were interviewed by trained staff. A 58-item questionnaire was primarily developed in German and then translated into three different languages to reach non-German-speaking patients., Results: A total of 606 patients were included in the study: 54.1% (328) were interviewed directly, 9.1% (55) participated via an online survey, and 36.8% (223) used the paper print version. More than one quarter, 27.4% (166) of the participants, had a migrant background. The majority of migrants and NM were highly satisfied with the communication with their doctors. First-generation migrants (FGM) and patients with breast cancer were less often informed about participation in clinical trials (p < 0.05) and 24.5% of them suggested the help of an interpreter to improve the medical consultation. Second and third-generation migrants (SGM and TGM) experienced more fatigue and nausea than expected., Conclusions: Our results allow the hypothesis that training medical staff in intercultural competence and using disease-related patient information in different languages can improve best supportive care management and quality of life in cancer patients with migrant status., (© 2021. The Author(s).)

The effectiveness of postoperative radiotherapy (PORT) in improving outcomes remains debatable for oral squamous cell carcinoma (OSCC) patients with pathological intermediate-risk factors (IRFs) after surgery. A retrospective analysis was conducted on 432 intermediate-risk OSCC patients defined by histological reporting of close margin (<5mm), early nodal disease (pN1), depth of invasion/tumour thickness ≥5mm, perineural invasion, and/or lymphovascular invasion. Outcomes measured were disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). PORT was associated with an improvement in 5-year DFS on univariable analysis (80% vs 71%; P=0.044), but this did not remain significant on multivariable analysis. PORT was not associated with differences in DSS or OS. The surgical salvage rate was similar in the PORT and surgery-only groups (41% vs 47%; P=0.972). Perineural invasion was found to be an independent predictor of inferior DSS (hazard ratio (HR) 2.19), DFS (HR 1.89), and OS (HR 1.97). Significantly worse outcomes were observed for patients with ≥4 concurrent IRFs. The application of PORT was associated with lower rates of recurrence, but the benefit was less apparent on mortality. Patients with perineural invasion and multiple concurrent IRFs were found to be at greatest risk, representing a subset of intermediate-risk OSCC patients who may benefit from PORT., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Primary nonfunction (PNF) in the early postoperative period following liver transplantation is fatal if not managed appropriately with early retransplantation. Severe early allograft dysfunction can mimic PNF. The identification of treatable causative factors such as sepsis, hepatic artery, or portal vein thrombosis is essential to distinguish it from PNF, and their early management may avoid the need for retransplantation. In this article, we describe a case of sepsis-induced severe liver dysfunction from a contaminated graft perfused with normothermic machine perfusion (NMP), which presented in a manner similar to PNF. The implications of graft contamination are poorly described. To our knowledge, this is the first report of bacterial contamination of a graft that underwent NMP and subsequently caused severe sepsis in the recipient. The conditions created with NMP may be optimal for certain micro-organisms to thrive. The role of the liver in the immune system is complex as it provides an essential barrier to enterically derived portal venous pathogens and produces numerous acute phase proteins that augment the systemic immune response. Additionally, the liver is also known to restrain harmful and excessive systemic immune responses such as those that occur with the sepsis syndrome. The relationship between bacterial graft contamination, sepsis, and graft dysfunction may be multidirectional., (Copyright © 2020. Published by Elsevier Inc.)

Background: Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care., Methods: The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions., Results: We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures., Conclusions: We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.

Aim: The main aim of this study is to evaluate the interest of three-dimensional ultrasound perineal in the measurement of the levator hiatus area as an objective reflection of the surgical correction of pelvic organ prolapse (POP). Our hypothesis is that POP surgery decreases the size of the levator hiatus area., Materials and Methods: A longitudinal and prospective study was conducted between April and July 2017 in the Department of Gynaecology & Obstetrics at University Hospital of Angers. Surgery was performed either by laparoscopy (sacrocolpopexy) or vaginal surgery (with or without the use of mesh). All patients were handed an information letter and signed an informed consent before being included in the study. A questionnaire was fullfilled before and one month after surgery. A clinical evaluation using the simplified POP-Q classification and a perineal 3D ultrasound were carried out before and after surgery by the same professional. The levator hiatus area was assessed before and after surgery in order to evaluate the impact of surgery on the levator hiatus area. Simplified POP-Q measurements and responses to PFDI-20 and PFDI-7 questionnaires were also collected., Results: A total of 18 patients were included in the study and four were excluded. Seven underwent laparoscopic surgery and seven underwent vaginal surgery. The levator hiatus area decreased substantially from 20.87 to 16.55cm 2 on mean (p=0.0001) at rest. Regarding patient satisfaction, the PFDI-20 score improved after surgery from 89.36 to 37.87 on mean (p=0.006), but the PFIQ-7 score did not reveal any significant changes (p=0.096). For the clinical examination, we used the simplified POP-Q with Ba measurement from 2.3 to -1.92cm (p=0.005) or Bp from -1.5 to -2.46cm, which is not a significant change (p=0.14). Points C (or D in cases with a history of hysterectomy) changed from -3.1 to -6.15cm (p=0.03)., Conclusion: The levator hiatus area seems to decrease after POP surgery. 3D ultrasound seems a new and complementary procedure that allowed to evaluate objectively the levator hiatus area and thus the clinical findings of the surgery., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: The impact of the Covid-19 pandemic on the 11 million people currently incarcerated worldwide is the subject of many concerns. Prisons and jails are filled with people suffering from many preexisting medical conditions increasing the risk of complications. Detainees' access to medical services is already limited and overcrowding poses a threat of massive contagion. Beyond the health impact of the crisis, the tightening of prison conditions worries. On March 16, 2020, in France, the lockdown measures have been accompanied by specific provisions for prisons: all facilities have suspended visitations, group activities and external interventions. Over 10,000 prisoners have been released to reduce the prison population and the risk of virus propagation. These adjustments had major consequences on the healthcare system in French prisons. The objectives of this article are to describe the reorganization of the three levels of psychiatric care for inmates in France in the context of Covid-19 pandemic and to have a look at the impact of lockdown measures and early releases on mental health of prisoners., Methods: This work is based on a survey conducted in April 2020 in France among psychiatric healthcare providers working in 42 ambulatory units for inmates and in the 9 full-time inpatient psychiatric wards exclusively for inmates called "UHSAs" (which stands for "unités hospitalières spécialement aménagées", and can be translated as "specially equipped hospital units"). A review of the international literature on mental healthcare system for inmates during the Covid-19 epidemic has also been performed., Results: The Covid-19 epidemic has been rather contained during the period of confinement in French prisons but the impact of confinement measures on the prison population is significant. The three levels of psychiatric care for inmates have implemented specific measures to ensure continuity of care, to support detainees during Coronavirus lockdown and to prevent an infection's spread. Among the most important are: limitation of medical consultations to serious and urgent cases, creation of "Covid units", cancellation of voluntary psychiatric hospitalizations, reinforcement of preventive hygiene measures and reshuffling of medical staff. Prolonged confinement has consequences on mental health of detainees. Currently, mental health workers are facing multiple clinical situations such as forced drug and substance withdrawal (linked to difficulties in supplying psychoactive substances), symptoms of anxiety (due to concerns for their own and their relatives' well-being) and decompensation among patients with severe psychiatric conditions. Early releases from prison may also raise some issues. People recently released from prison are identified as at high risk of death by suicide and drug overdose. The lack of time to provide the necessary link between health services within prisons and health structures outside could have serious consequences, emphasizing the well-known "revolving prison doors" effect., Discussion: The current lockdown measures applied in French jails and prisons point out the disparities between psychiatric care for inmates and psychiatric care for general population. Giving the high vulnerability of prison population, public health authorities should pay more attention to health care in prisons., (Copyright © 2020 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Targeted delivery to specific tissues and subcellular compartments is of paramount importance to optimize therapeutic or diagnostic interventions while minimizing side-effects. Using recently identified LDL receptor (LDLR) -targeting small synthetic peptide-vectors conjugated to model cargos of different nature and size, we investigated in LDLR-expressing cells the impact of vector-cargo molecular engineering and coupling valency, as well as the cellular exposure duration on their target engagement and intracellular trafficking and delivery profiles. All vector-cargo conjugates evaluated were found to be delivered to late compartments together with the natural ligand LDL, although to varying extents and with different kinetics. Partial recycling together with the LDLR was also consistently observed. Under continuous cellular exposure, the extent of intracellular vector-cargo delivery primarily relies on their endosomal unloading potential. In this condition, the highest intracellular delivery potential was observed with a monovalent conjugate displaying a rather high LDLR dissociation rate. On the contrary, under transient cellular exposure followed by chase, low dissociation-rate bivalent conjugates revealed a higher intracellular delivery potential than the monovalent conjugate. This was shown to rely on their ability to undergo multiple endocytosis-recycling rounds, with limited release in the ligand-free medium. The absence of reciprocal competition with the natural ligand LDL on their respective intracellular trafficking was also demonstrated, which is essential in terms of potential safety liabilities. These results demonstrate that not only molecular engineering of new therapeutic conjugates of interest, but also the cellular exposure mode used during in vitro evaluations are critical to anticipate and optimize their delivery potential., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ballast water discharges may cause negative impacts to aquatic ecosystems, human health and economic activities by the introduction of potentially harmful species. Fifty untreated ballast water tanks, ten in each port, were sampled in four Adriatic Italian ports and one Slovenian port. Salinity, temperature and fluorescence were measured on board. Faecal indicator bacteria (FIB), phyto- and zooplankton were qualitatively and quantitatively determined to identify the species assemblage arriving in ballast water. FIB exceeded the convention standard limits in 12% of the sampled tanks. Vibrio cholerae was not detected. The number of viable organisms in the size groups (minimum dimension) <50 and ≥10 μm and ≥50 μm resulted above the abundances required from the Ballast Water Management Convention in 55 and 86% of the samples, respectively. This is not surprising as unmanaged ballast waters were sampled. Some potentially toxic and non-indigenous species were observed in both phyto- and zooplankton assemblages., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Approximately 21% of Germany's inhabitants have been born abroad or are of direct descent of immigrants. A positive birth experience has an effect on a woman's mental health and her future family planning choices. While international studies showed that immigrant women are less satisfied with their birth experience, no such study has been conducted in Germany until now., Methods: At our center of tertiary care in Berlin, with approximately 50% immigrants among patients, pregnant women of at least 18 years of age were offered participation in this study. A modified version of the Migrant Friendly Maternity Care Questionnaire (MFMCQ) designed by Gagnon et al. in German, English, French, Spanish, Arabic and Turkish was used. We compared non-immigrant women to immigrant women and women with direct descent of immigrants. For certain analysis, the latter two groups were included together under the category "migration background"., Results: During the study period, 184 non-immigrant, 214 immigrant women and 62 direct descendants of immigrants were included. The most frequent countries of origin were Syria (19%), Turkey (17%), and Lebanon (9%). We found a slight difference between groups regarding age (non-immigrants: mean 33 years versus women with any migration background: mean 31) as well as parity with more non-immigrants delivering their first child. No difference in the satisfaction with care was observed between immigrant and any migration background groups (p ≥ 0.093 in the two-sided Fisher's exact test). At least 75.8% of all participating women reported complete satisfaction with care during labor, birth and after birth. Interestingly, the level of German language proficiency did not influence the immigrant patient's satisfaction with care., Conclusion: The study results show no difference regarding overall satisfaction with care during labor and birth despite a relevant language barrier. We are for the first time providing the MFMCQ in German and Turkish. Further future analyses on the impact of patient expectations on satisfaction with care will be conducted.

Background: Traditional medical education strategies teach learners how to correctly perform procedures while neglecting to provide formal training on iatrogenic error management. Error management training (EMT) requires active exploration as well as explicit encouragement for learners to make and learn from errors during training. Simulation provides an excellent methodology to execute a curriculum on iatrogenic procedural complication management. We hypothesize that a standardized simulation-based EMT curriculum will improve learner's confidence, cognitive knowledge, and performance in iatrogenic injury management., Methods: This was a pilot, prospective, observational study performed in a simulation center using a curriculum developed to educate resident physicians on iatrogenic procedural complication management. Pre- and postintervention assessments included confidence surveys, cognitive questionnaires, and critical action checklists for six simulated procedure complications. Assessment data were analyzed using medians and interquartile ranges (IQRs), and the paired change scores were tested for median equality to zero via Wilcoxon signed rank tests with p < 0.05 considered statistically significant., Results: Eighteen residents participated in the study curriculum. The median (IQR) confidence increased significantly by a summed score of 12.5 (8.75-17.25; p < 0.001). Similarly, the median (IQR) knowledge significantly increased by 6 (3-8) points from the pre- to postintervention assessment (p < 0.001). For each of the simulation cases, the number of critical actions performed increased significantly (p < 0.001 to p = 0.002)., Conclusion: We demonstrated significant improvement in the confidence, clinical knowledge, and performance of critical actions after the completion of this curriculum. This pilot study provides evidence that a structured EMT curriculum is an effective method to teach management of iatrogenic injuries.

Thlaspi arvense (pennycress) has the potential for domestication as a new oilseed crop. Information from an extensive body of research on the related plant species Arabidopsis can be used to greatly speed this process. Genome-scale comparisons in this paper documented that pennycress and Arabidopsis share similar gene duplication. This finding led to the hypothesis that it should be possible to isolate Arabidopsis-like mutants in pennycress. This proved to be true, as forward genetic screens identified floral and vegetative pennycress mutants that were similar to mutants found in Arabidopsis. Extending this approach, it was shown that most of the pennycress genes responsible for the formation of oxidized tannins could be rapidly identified. The causative mutations in the pennycress mutants could be identified either by PCR amplification of candidate genes or through whole-genome sequencing (WGS) analysis. In all, WGS was used to characterize 95 ethyl methane sulfonate mutants, which revealed a mutation rate of 4.09 mutations per megabase. A sufficient number of non-synonymous mutations were identified to create a mutant gene index that could be used for reverse genetic approaches to identify pennycress mutants of interest. As proof of concept, a Ta-max3-like dwarf mutant and Ta-kcs5/cer60-like wax mutants deficient in the biosynthesis of long chain fatty acids were identified. Overall, these studies demonstrate that translational genomics can be used to promote the domestication of pennycress. Furthermore, the ease with which important findings could be made in pennycress makes this species a new potential model plant., (© 2018 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.)