The mucus layer is a hydrogel network that covers mucosal surfaces of the human body. Mucus has important protective properties that are related to its unique rheological properties, which are based on mucins being the main glycoprotein constituents. Mucin macromolecules entangle with one another and form a physical network that is instrumental for many important defense functions. Mucus derived from various human or animal sources is poorly defined and thus not suitable for many application purposes. Herein, a synthetic route is fabricated to afford a library of compositionally defined mucus-inspired hydrogels (MIHs). MIHs are synthesized by thiol oxidation to render disulfide bonds between the crosslinker ethoxylated trimethylolpropane tri(3-mercaptopropionate) (THIOCURE ETTMP 1300) and the linear precursors, dithiolated linear polyglycerol (LPG(SH)2) or polyethylene glycol (PEG(SH)2) of different molecular weights. The mixing ratio of linear polymers versus crosslinker and the length of the linear polymer are varied, thus delivering a library of compositionally defined mucin-inspired constructs. Their viscoelastic properties are determined by frequency sweeps at 25 and 37 °C and compared to the corresponding behavior of native human mucus. Here, MIHs composed of a 10:1 ratio of LPG(SH)2 and ETTMP 1300 are proved to be the best comparable to human airway mucus rheology.

Background: The COVID-19 pandemic triggered countermeasures like #StayAtHome initiatives, which have changed the whole world. Despite the success of such initiatives in limiting the spread of COVID-19 to #FlattenTheCurve, physicians are now confronted with the adverse effects of the current restrictive pandemic management strategies and social distancing measures.

Objective: We aim to draw attention to the particular importance and magnitude of what may be the adverse effects of COVID-19-related policies.

Methods: We herein report a case of an otherwise healthy 84-year-old woman with deep vein thrombosis (DVT) due to COVID-19-related directives. #StayAtHome policies and consequential social isolation have diminished our patient's social life and reduced her healthy movement behaviors. The patient spent long hours in a seated position while focusing on the intensive flow of media information regarding the pandemic.

Results: Reduced mobility due to preventive social isolation during the COVID-19 pandemic was the only identified cause of the DVT.

Conclusions: While evaluating the effect of the COVID-19 pandemic and governmentally implemented containment measures, including social isolation and mobility reduction, adverse events should be considered. Digital approaches might play a crucial role in supporting public health.

Background: Despite the high prevalence of child sexual offenses and the increasing amounts of available child sexual abuse material, there is a global shortage of preventive interventions focusing on individuals at risk of sexual offending. The web-based app Troubled Desire aims to address this shortage by offering self-assessments and self-management training modules in different languages to individuals with sexual interests in prepubescent and early pubescent children (ie, those with pedophilic and hebephiliac sexual interest, respectively).

Objective: The aim of this study was to describe the characteristics of the users of the Troubled Desire app.

Methods: The fully completed self-assessment data gathered within the first 30 months of this study from October 25, 2017 to April 25, 2020 were investigated. The main outcome measures were (1) sociodemographic information and (2) sexual interests and sexual behaviors of the users of Troubled Desire.

Results: The self-assessment was completed by 4161 users. User accesses were mainly from Germany (2277/4161, 54.7%) and the United States (474/4161, 11.4%). Approximately 78.9% (3281/4161) of the users reported sexual interest in children; these users were significantly more likely to report distress and trouble owing to their sexual interest. Further, child sexual offenses and consumption of child sexual abuse material were significantly more common among users with sexual interest in children than among users with no sexual interest in children. Additionally, the majority of the offenses were not known to legal authorities.

Conclusions: The Troubled Desire app is useful in reaching out to individuals with sexual interest in prepubescent and early pubescent children. However, future research is warranted to understand the prospective relevance of the Troubled Desire app in the prevention of child sexual offending.

Patients with kidney failure have notoriously weak responses to common vaccines. Thus, immunogenicity of novel SARS-CoV-2 vaccines might be impaired in this group. To determine immunogenicity of SARS-CoV-2 vaccination in patients with chronic dialysis, we analyzed the humoral and T-cell response after two doses of mRNA vaccine Tozinameran (BNT162b2 BioNTech/Pfizer). This observational study included 43 patients on dialysis before vaccination with two doses of Tozinameran 21 days apart. Overall, 36 patients completed the observation period until three weeks after the second dose and 32 patients were further analyzed at week 10. Serum samples were analyzed by SARS-CoV-2 specific IgG and IgA antibodies ~1, ~3-4 and ~10 weeks after the second vaccination. In addition, SARS-CoV-2-specific T-cell responses were assessed at ~3-4 weeks by an interferon-gamma release assay (IGRA). Antibody and T cell outcomes at this timepoint were compared to a group of 44 elderly patients not on dialysis, after immunization with Tozinameran. Median age of patients on chronic dialysis was 74.0 years (IQR 66.0, 82.0). The proportion of males was higher (69.4%) than females. Only 20/36 patients (55.6%, 95%CI: 38.29-71.67) developed SARS-CoV-2-IgG antibodies at the first sampling, whereas 32/36 patients (88.9%, 95%CI: 73.00-96.38) demonstrated IgG detection at the second sampling. In a longitudinal follow-up at ~10 weeks after the second dose, the proportion of dialysis patients reactive for anti-SARS-CoV-2-IgG decreased to 27/32 (84.37%, 95%CI: 66.46-94.10) The proportion of anti-SARS-CoV-2 S1 IgA decreased from 33/36 (91.67%; 95%CI: 76.41-97.82) at weeks 3-4 down to 19/32 (59.38; 95%CI: 40.79-75.78). Compared to a cohort of vaccinees with similar age but not on chronic dialysis seroconversion rates and antibody titers were significantly lower. SARS-CoV-2-specific T-cell responses 3 weeks after second vaccination were detected in 21/31 vaccinated dialysis patients (67.7%, 95%CI: 48.53-82.68) compared to 42/44 (93.3%, 95%CI: 76.49-98.84) in controls of similar age. Patients on dialysis demonstrate a delayed, but robust immune response three to four weeks after the second dose, which indicates effective vaccination of this vulnerable group. However, the lower immunogenicity of Tozinameran in these patients needs further attention to develop potential countermeasures such as an additional booster vaccination.

Despite RT-PCR confirmed COVID-19, specific antibodies to SARS-CoV-2 spike are undetectable in serum in approximately 10% of convalescent patients after mild disease course. This raises the question of induction and persistence of SARS-CoV-2-reactive T cells in these convalescent individuals. Using flow cytometry, we assessed specific SARS-CoV-2 and human endemic coronaviruses (HCoV-229E, -OC43) reactive T cells after stimulation with spike and nucleocapsid peptide pools and analyzed cytokine polyfunctionality (IFNγ, TNFα, and IL-2) in seropositive and seronegative convalescent COVID-19 patients as well as in unexposed healthy controls. Stimulation with SARS-CoV-2 spike and nucleocapsid (NCAP) as well as HCoV spike peptide pools elicited a similar T cell response in seropositive and seronegative post COVID-19 patients. Significantly higher frequencies of polyfunctional cytokine nucleocapsid reactive CD4+ T cells (triple positive for IFNγ, TNFα, and IL-2) were observed in both, seropositive (p = 0.008) and seronegative (p = 0.04), COVID-19 convalescent compared to healthy controls and were detectable up to day 162 post RT-PCR positivity in seronegative convalescents. Our data indicate an important role of NCAP-specific T cells for viral control.

The political debate over the inclusion of refugees frequently revolves around cultural differences, in particular differences pertaining to values, which are suspected to hamper social integration. Sociological accounts of values in principle warrant the assumption that different values promote conflict over sensitive social issues. However, only little is known about the actual values of refugees who recently arrived in many European countries. Comparative values research suggests that immigrants from culturally distant countries increase value heterogeneity. In contrast, acculturation and assimilation theories argue that values are not static constructs, but subject to change and transformation. Using data from the IAB-BAMF-SOEP survey, a representative panel of refugees in Germany, and from the World Values Survey, the present study investigates differences in liberal democratic and gender equality values between refugees and German citizens. Results indicate that refugees from almost all countries investigated show higher levels of agreement to these values, except secularism, than Germans.

At the end of last year, on the occasion of the publication of an exciting new study, several reports went through the press such as "Human-made stuff now outweighs all life on Earth" (Scientific American), "Human-made materials now weigh more than the Earth's entire biomass" (The Guardian) or "Human-made mass exceeds biomass for the first time in 2020" (Bayerischer Rundfunk). In fact, the new study published in the renowned scientific journal Nature on 9.12.2020 was also titled "Global human-made mass exceeds all living biomass" (Elhacham et al. 2020). In the meantime, I have been asked several times whether the Anthropocene Working Group (AWG) (and thus also I) has not already come up with completely different, orders of magnitude higher values for the mass of the "technosphere" at the end of 2016 and how this new study fits in. Such questions, as well as the metabolism metaphor often used in my recent Scilogs blogposts to compare the biosphere and the technosphere, but also the creation of some new number-based graphs for lectures, current talks and a paper in preparation, are what I take as an opportunity to compare the different approaches in more detail in this post. (this is the english version of an online article based on several invited talks, and posted on Scilogs/Springer under https://scilogs.spektrum.de/der-anthropozaeniker/die-menschengemachte- masse-darfs-ein-bisschen-mehr-sein/ (An extended version on the topic with other members of the Anthopocene Working Group is in preparation)

Obstructive sleep apnea (OSA), a heterogeneous and multifactorial sleep related breathing disorder with high prevalence, is a recognized risk factor for cardiovascular morbidity and mortality. Autonomic dysfunction leads to adverse cardiovascular outcomes in diverse pathways. Heart rate is a complex physiological process involving neurovisceral networks and relative regulatory mechanisms such as thermoregulation, renin-angiotensin-aldosterone mechanisms, and metabolic mechanisms. Heart rate variability (HRV) is considered as a reliable and non-invasive measure of autonomic modulation response and adaptation to endogenous and exogenous stimuli. HRV measures may add a new dimension to help understand the interplay between cardiac and nervous system involvement in OSA. The aim of this review is to introduce the various applications of HRV in different aspects of OSA to examine the impaired neuro-cardiac modulation. More specifically, the topics covered include: HRV time windows, sleep staging, arousal, sleepiness, hypoxia, mental illness, and mortality and morbidity. All of these aspects show pathways in the clinical implementation of HRV to screen, diagnose, classify, and predict patients as a reasonable and more convenient alternative to current measures.

The COVID-19 pandemic has led to significant changes around the world, including changes in education. Almost immediately after school closures were imposed in March 2020 and students in many cases had to take digital distance learning classes, educational researchers clearly pointed out that this could contribute to a worsening of existing social inequalities in education. How has this research knowledge been publicly received? This question was investigated with a discourse study framed in terms of innovation theory which analyzed a total of 88 texts from three German Internet platforms covering the period between March and September 2020. The results show that with regard to the consideration of social inequality, two barely connected worlds exist (one in research, one in the professional public). In the professional public discourse, research knowledge plays a subordinate role at best. Moreover, in the public discourse two strands of discourse are found that are also not intertwined. The results are discussed in terms of their significance for trust in educational institutions, the care and maintenance of which is a relevant topic for educational policy and management, particularly in times of disruptive changes in educational practice.

Introduction:

While parenting interventions are flourishing in low/middle-income countries (LMICs), their ethical challenges have rarely been considered. We therefore applaud Weber and colleagues1 for their contribution to a recent debate about the ethics of parenting interventions.2 3 To apply the principles of beneficence, autonomy and justice to such interventions is certainly valuable, especially if ‘respect for autonomy’ includes consideration of additional ethical principles the targeted communities uphold. We also agree that ‘recognising and integrating existing beliefs, practices, people, context and skills’1 in the programme design is crucial to fulfil the three principles. Finally, we agree most emphatically that there are considerable biases in the underlying research as it tends to ‘only measure constructs that are valued from a western perspective’.1 However, it is our contention that the authors fail to apply these insights to the science on which they build their arguments. To fully acknowledge biases in the knowledge base of early childhood development (ECD), we argue, is a fundamental requirement to meet the principles they propose.

Plant–soil systems are key for understanding the effects of factors of global change. Recent work has highlighted the general importance of considering the simultaneous incidence of some factors or stressors. To help mechanistically dissect the possible interactions of such factors, we here propose three broad groups of mechanisms that may generally lead to nonadditivity of responses within a plant–soil system: direct factor interactions (that is one factor directly changing another), within-plant information processing and crosstalk, and effects of factors on groups of soil biota interacting with plants. Interactions are also possible within and across these groups. Factor interactions are very likely to be present in experiments, especially when dealing with an increasing number of factors. Identifying the nature of such interactions will be essential for understanding and predicting global change impacts on plants and soil.

Objective: To assess the safety and efficacy of epigallocatechin-3-gallate (EGCG) add-on to glatiramer acetate (GA) in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: We enrolled patients with RRMS (aged 18-60 years, Expanded Disability Status Scale [EDSS] score 0-6.5), receiving stable GA treatment in a multicenter, prospective, double-blind, phase II, randomized controlled trial. Participants received up to 800 mg oral EGCG daily over a period of 18 months. The primary outcome was the proportion of patients without new hyperintense lesions on T2-weighted (T2w) brain MRI within 18 months. Secondary end points included additional MRI and clinical parameters. Immunologic effects of EGCG were investigated in exploratory experiments.

Results: A total of 122 patients on GA were randomly assigned to EGCG treatment (n = 62) or placebo (n = 60). We could not demonstrate a difference between groups after 18 months for the primary outcome or other radiologic (T2w lesion volume, T1w hypointense lesion number or volume, number of cumulative contrast-enhancing lesions, percent brain volume change), or clinical (EDSS, MS functional composite, and annualized relapse rate) parameter. EGCG treatment did not affect immune response to GA. Pharmacologic analysis revealed wide ranging EGCG plasma levels. The treatment was well tolerated with a similar incidence of mostly mild adverse events similar in both groups.

Conclusion: In RRMS, oral EGCG add-on to GA was not superior to placebo in influencing MRI and clinical disease activity over 18 months. The treatment was safe at a daily dosage up to 800 mg EGCG. It did not influence immune parameters, despite indication of EGCG being bioavailable in patients. Classification of Evidence This study provides Class II evidence that for patients with RRMS, EGCG added to GA did not significantly affect the development of new hyperintense lesions on T2-weighted brain MRI.

Citizen science is an approach that has become increasingly popular in recent years. Despite this growing popularity, there still is widespread scepticism in the academic world about the validity and quality of data from citizen science projects. And although there might be great potential, citizen science is a rarely used approach in the field of bioacoustics. To better understand the possibilities, but also the limitations, we here evaluated data generated in a citizen science project on nightingale song as a case study. We analysed the quantity and quality of song recordings made in a non-standardized way with a smartphone app by citizen scientists and the standardized recordings made with professional equipment by academic researchers. We made comparisons between the recordings of the two approaches and among the user types of the app to gain insights into the temporal recording patterns, the quantity and quality of the data. To compare the deviation of the acoustic parameters in the recordings with smartphones and professional devices from the original song recordings, we conducted a playback test. Our results showed that depending on the user group, citizen scientists produced many to a lot of recordings of valid quality for further bioacoustic research. Differences between the recordings provided by the citizen and the expert group were mainly caused by the technical quality of the devices used—and to a lesser extent by the citizen scientists themselves. Especially when differences in spectral parameters are to be investigated, our results demonstrate that the use of the same high-quality recording devices and calibrated external microphones would most likely improve data quality. We conclude that many bioacoustic research questions may be carried out with the recordings of citizen scientists. We want to encourage academic researchers to get more involved in participatory projects to harness the potential of citizen science—and to share scientific curiosity and discoveries more directly with society.

The oomycete Aphanomyces astaci is the etiologic agent of crayfish plague, a disease that has seriously impacted the populations of European native crayfish species. The introduction of non-indigenous crayfish of North American origin and their wide distribution across Europe have largely contributed to spread of crayfish plague in areas populated by indigenous crayfish. Tracking A. astaci genotypes may thus be a useful tool for investigating the natural history of crayfish plague in its European range, as well as the sources and introduction pathways of the pathogen. In this study, we describe the development of real-time PCR TaqMan assays aiming to distinguish the five genotype groups of A. astaci (A–E) previously defined by their distinct RAPD patterns. The method was evaluated using DNA extracts from pure A. astaci cultures representing the known genotype groups, and from A. astaci-positive crayfish clinical samples collected mostly during crayfish plague outbreaks that recently occurred in Central Italy and Czechia. The assays do not cross-react with each other, and those targeting genotype groups A, B, D, and E seem sufficiently specific to genotype the pathogen from infected crayfish in the areas invaded by A. astaci (particularly Europe). The unusual A. astaci genotype “SSR-Up” documented from crayfish plague outbreaks in Czechia and chronically infected Pontastacus leptodactylus in the Danube is detected by the group B real-time PCR. The assay originally developed to detect group C (one not yet documented from crayfish plague outbreaks) showed cross-reactivity with Aphanomyces fennicus; the A. astaci genotype “rust1” described in the United States from Faxonius rusticus is detected by that assay as well. Analyses of additional markers (such as sequencing of the nuclear internal transcribed spacer or mitochondrial ribosomal subunits) may complement such cases when the real-time PCR-based genotyping is not conclusive. Despite some limitations, the method is a robust tool for fast genotyping of A. astaci genotype groups common in Europe, both during crayfish plague outbreaks and in latent infections.

The expression of the genes encoding the inhibitors of serine (ISP) and cysteine ​​proteinases (ICP) was studied in the roots of tomato plants resistant and susceptible to the root-knot nematode Meloidogyne incognita during infection and under the effects of signaling molecules: salicylic (SA) and jasmonic (JA) acids. It was shown that, upon infection, resistant plants are characterized by an increased accumulation of transcripts of the ICP and ISP genes at the stages of penetration and development in the roots, while the level of transcription does not change in susceptible plants. There was a significant decrease in nematode invasion in susceptible plants after treatment with SA or JA compared to untreated plants, which makes it possible to determine the role of the studied proteinase inhibitors in resistance induced by signaling molecules. It was revealed that an increase in expression of the genes of proteinase inhibitors is accompanied by inhibition of the reproductive potential and size of M. incognita females, as well as by a decrease in plant infection.

Several types of psychological treatment for posttraumatic stress disorder (PTSD) are considered well established and effective, but evidence of their long-term efficacy is limited. This systematic review and meta-analysis aimed to investigate the long-term outcomes across psychological treatments for PTSD. MEDLINE, Cochrane Library, PTSDpubs, PsycINFO, PSYNDEX, and related articles were searched for randomized controlled trials with at least 12 months of follow-up. Twenty-two studies (N = 2638) met inclusion criteria, and 43 comparisons of cognitive behavioral therapy (CBT) were available at follow-up. Active treatments for PTSD yielded large effect sizes from pretest to follow-up and a small controlled effect size compared with non-directive control groups at follow-up. Trauma-focused treatment (TFT) and non-TFT showed large improvements from pretest to follow-up, and effect sizes did not significantly differ from each other. Active treatments for comorbid depressive symptoms revealed small to medium effect sizes at follow-up, and improved PTSD and depressive symptoms remained stable from treatment end to follow-up. Military personnel, low proportion of female patients, and self-rated PTSD measures were associated with decreased effect sizes for PTSD at follow-up. The findings suggest that CBT for PTSD is efficacious in the long term. Future studies are needed to determine the lasting efficacy of other psychological treatments and to confirm benefits beyond 12-month follow-up.

Herpes zoster, the result of varicella-zoster virus (VZV) reactivation, is frequently complicated by difficult-to-treat chronic pain states termed postherpetic neuralgia (PHN). While there are no animal models of VZV-induced pain following viral reactivation, subcutaneous VZV inoculation of the rat causes long-term nocifensive behaviors indicative of mechanical and thermal hypersensitivity. Previous studies using UV-inactivated VZV in the rat model suggest viral gene expression is required for the development of pain behaviors. However, it remains unclear if complete infection processes are needed for VZV to induce hypersensitivity in this host. To further assess how gene expression and replication contribute, we developed and characterized three replication-conditional VZV using a protein degron system to achieve drug-dependent stability of essential viral proteins. Each virus was then assessed for induction of hypersensitivity in rats under replication permissive and nonpermissive conditions. VZV with a degron fused to ORF9p, a late structural protein that is required for virion assembly, induced nocifensive behaviors under both replication permissive and nonpermissive conditions, indicating that complete VZV replication is dispensable for the induction of hypersensitivity. This conclusion was confirmed by showing that a genetic deletion recombinant VZV lacking DNA packaging protein ORF54p still induced prolonged hypersensitivities in the rat. In contrast, VZV with a degron fused to the essential IE4 or IE63 proteins, which are involved in early gene regulation of expression, induced nocifensive behaviors only under replication permissive conditions, indicating importance of early gene expression events for induction of hypersensitivity. These data establish that while early viral gene expression is required for the development of nocifensive behaviors in the rat, complete replication is dispensable. We postulate this model reflects events leading to clinical PHN, in which a population of ganglionic neurons become abortively infected with VZV during reactivation and survive, but host signaling becomes altered in order to transmit ongoing pain.

Current mass drug administration (MDA) programs for the treatment of human river blindness (onchocerciasis) caused by the filarial worm Onchocerca volvulus rely on ivermectin, an anthelmintic originally developed for animal health. These treatments are primarily directed against migrating microfilariae and also suppress fecundity for several months, but fail to eliminate adult O. volvulus. Therefore, elimination programs need time frames of decades, well exceeding the life span of adult worms. The situation is worsened by decreased ivermectin efficacy after long-term therapy. To improve treatment options against onchocerciasis, a drug development candidate should ideally kill or irreversibly sterilize adult worms. Emodepside is a broad-spectrum anthelmintic used for the treatment of parasitic nematodes in cats and dogs (Profender and Procox). Our current knowledge of the pharmacology of emodepside is the result of more than 2 decades of intensive collaborative research between academia and the pharmaceutical industry. Emodepside has a novel mode of action with a broad spectrum of activity, including against extraintestinal nematode stages such as migrating larvae or macrofilariae. Therefore, emodepside is considered to be among the most promising candidates for evaluation as an adulticide treatment against onchocerciasis. Consequently, in 2014, Bayer and the Drugs for Neglected Diseases initiative (DNDi) started a collaboration to develop emodepside for the treatment of patients suffering from the disease. Macrofilaricidal activity has been demonstrated in various models, including Onchocerca ochengi in cattle, the parasite most closely related to O. volvulus. Emodepside has now successfully passed Phase I clinical trials, and a Phase II study is planned. This Bayer–DNDi partnership is an outstanding example of “One World Health,” in which experience gained in veterinary science and drug development is translated to human health and leads to improved tools to combat neglected tropical diseases (NTDs) and shorten development pathways and timelines in an otherwise neglected area.

Increasing demands on ecosystems, decreasing biodiversity, and climate change are among the most pressing environmental issues of our time. As changing weather conditions are leading to increased vector-borne diseases and heat- and flood-related deaths, it is entering collective consciousness: environmental issues are human health issues. In public health, the field addressing these issues is known as environmental health. This field addresses both the effects people have on their environment as well as the effects of the environment on people. Psychology, as a discipline concerned with explaining, predicting, and changing behavior has much to contribute to these issues because human behavior is key in promoting environmental health. To date, however, an integrative view of environmental health in psychology is lacking, hampering urgently needed progress. In this paper, we review how the environment and human health are intertwined, and that much can be gained through a systemic view of environmental health in psychology. Based on a review of the literature, we suggest that psychologists unite efforts to promote an integrative science and practice of environmental health psychology, and jointly address environmental-health related behavior. The research agenda for this field will include integrating behavior change theory and intervention approaches. Thereby, psychology can potentially make an important contribution to sustained environmental health for generations to come.

One of the major reasons for a recent stuck of the development of kesterite based photovoltaic devices is related to the problems in their open circuit voltage. Several limitations can be pointed out as a possible origin. In particular, for a case of Cu and Zn containing kesterite compounds, a lattice disorder connected to these cations is considered to bring in an important contribution to the limitations above. Extensive studies showed a significant influence of this disorder being an intrinsic property of kesterites to structural, optical and vibrational properties of the related materials. However, detailed investigations focused to the role of disorder in formation of the electrical properties of the kesterite materials are still lacking. In order to cover this gap, here is investigated resistivity of Cu2ZnSn(S1-xSex)4 (CZTSSe) powder samples with x = 0.48–1.00 at temperatures between ~ 10 and 300 K. A detailed analysis of the measured data permits to establish various conductivity mechanisms within different temperature ranges, and to obtain a set of important macroscopic and microscopic electronic parameters. By itself, their dependence on x does not reveal any univocal behavior. In contrast, all the electronic parameters above exhibit a clear correlation with the order parameter Q. This is explained completely by a strong sensitivity of the electronic properties of CZTSSe to the Cu/Zn disorder.