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Herein we present the synthesis of symmetrically and unsymmetrically substituted 1,3-bissulfanylbicyclo[1.1.1]pentanes from disulfides and [1.1.1]propellane. Bicyclo[1.1.1]pentanes (BCPs) recently gained interest as rigid linkers and as bioisosters of para-substituted benzene and alkyne moieties. The most promising precursor for BCPs is [1.1.1]propellane (1). The available methods to synthesize BCPs are quite limited and many groups contribute to the development of novel methods. The insertion of 1 into disulfide bonds is known, but has never been thoroughly investigated. In this study, we show that an UV initiated radical reaction can be used to synthesize symmetrically and unsymmetrically substituted BCP sulfides by reaction of [1.1.1]propellane (1) with disulfides. Depending on the ratio of 1 to the disulfide, only the BCP product (with up to 98% yield) or a mixture of BCP and [2]staffane can be obtained. The reaction tolerates functional groups such as halogens, alkyl and methoxy groups. The separation of the corresponding BCP and [2]staffane products is challenging but possible by column chromatography and preparative TLC in most cases. Single crystal X-ray diffraction analysis confirms the rod-like structure of the [2]staffanes that is often required in material applications.

Addictionology as a component of the health sciences is rapidly becoming recognized as a medical discipline, specifically as a subspecialty of psychiatry. The problem of addictions is a subject that extends and worsens in postmodern society, due to its multidimensionality and multifactoriality. The health conditions of the countries have improved in terms of reducing mortality and the incidence of some communicable diseases. However, there is a greater incidence of chronic noncommunicable diseases related to lifestyles, as well as the emergence of health problems derived from violence, drug consumption, social, recreational addictions and digital addiction (connectivity). Family factors, including rejection by parents and family conflicts, due to substance abuse and mental health problems, are among the strongest and most consistent predictors of adolescent behavior problems. Therefore, in the Holistic Family Centered Model, Nizama proposes integral human development through multidimensional organization as an axis of life that comprises eleven dimensions of human life: body, genetic potential, personality, human essence, cognition, imagination, lifestyles, assets, image, futurity and posterity. In conclusion, addictionology is the medical specialty indicated for the successful and hopeful management of this volitional disease in all age groups, with committed and sustainable family adherence. DOI:10.25176/RFMH.v19.n2.2078

2-Substituted hydrazinecarbothioamides and N,2-disubstituted hydrazinecarbothioamides react in high yield with dimethyl acetylenedicarboxylate (DMAD) to give 4-oxo-Z-(thiazolidin-5-ylidene) acetate derivatives. Several mechanistic options involving interaction are presented. The structures of thiazolidin-4-ones have been unambiguously confirmed by single crystal X-ray crystallography. Keywords: Hydrazinecarbothioamides, Dimethyl acetylenedicarboxylate, Thiazolidin-4-ones, X-ray crystallography

Subclinical left ventricular dysfunction is the most common cardiac complication after chemotherapy administration. Detection and early treatment are major issues for better cardiac outcomes in this cancer population. The most common definition of cardiotoxicity is a 10-percentage point decrease of left ventricular ejection fraction (LVEF) to a value

A series of C3-symmetric fully substituted benzenes were prepared based on alkyl triamino-benzene-tricarboxylates. Starting with a one step-synthesis, the alkyl triamino-benzene-tricarboxylates were synthesized using the corresponding cyanoacetates. The reactivity of these electronically sophisticated compounds was investigated by the formation of azides, the click reaction of the azides and a Sandmeyer-like reaction. Caused by the low stability of triaminobenzenes, direct N-alkylation was rarely reported. The use of the stable alkyl triamino-benzene-tricarboxylates allowed us total N-alkylation under standard alkylation conditions. The molecular structures of the C3-symmetric structures have been corroborated by an X-ray analysis.

The successful use of 1,3,4,2-triazaphospholenes (TAPs) as organo-catalysts stresses the need for efficient synthetic routes to these molecules. In this study, we establish the [1 + 4]-cycloaddition of PBr3 to azo-pyridines as a new approach to preparing pyrido-annellated TAPs in a single step from easily available precursors. The modular assembly of the azo-component via condensation of primary amines and nitroso compounds along with the feasibility of post-functionalization at the P–Br bond under conservation of the heterocyclic structure allows, in principle, to address a wide range of target molecules, which is illustrated by prototypical examples. The successful synthesis of a transition metal complex confirms for the first time the ability of a TAP to act as a P-donor ligand. Crystallographic studies suggest that hyperconjugation effects and intermolecular interactions induce a qualitatively similar ionic polarization of the P–Br bonds in TAPs as in better known isoelectronic diazaphospholenes.

Arctic sea-ice loss is emblematic of an amplified Arctic water cycle and has critical feedback implications for global climate. Stable isotopes (δ18O, δ2H, d-excess) are valuable tracers for constraining water cycle and climate processes through space and time. Yet, the paucity of well-resolved Arctic isotope data preclude an empirically derived understanding of the hydrologic changes occurring today, in the deep (geologic) past, and in the future. To address this knowledge gap, the Pan-Arctic Precipitation Isotope Network (PAPIN) was established in 2018 to coordinate precipitation sampling at 19 stations across key tundra, subarctic, maritime, and continental climate zones. Here, we present a first assessment of rainfall samples collected in summer 2018 (n = 281) and combine new isotope and meteorological data with sea ice observations, reanalysis data, and model simulations. Data collectively establish a summer Arctic Meteoric Water Line where δ2H = 7.6⋅δ18O–1.8 (r2 = 0.96, p < 0.01). Mean amount-weighted δ18O, δ2H, and d-excess values were −12.3, −93.5, and 4.9‰, respectively, with the lowest summer mean δ18O value observed in northwest Greenland (−19.9‰) and the highest in Iceland (−7.3‰). Southern Alaska recorded the lowest mean d-excess (−8.2%) and northern Russia the highest (9.9‰). We identify a range of δ18O-temperature coefficients from 0.31‰/°C (Alaska) to 0.93‰/°C (Russia). The steepest regression slopes (>0.75‰/°C) were observed at continental sites, while statistically significant temperature relations were generally absent at coastal stations. Model outputs indicate that 68% of the summer precipitating air masses were transported into the Arctic from mid-latitudes and were characterized by relatively high δ18O values. Yet 32% of precipitation events, characterized by lower δ18O and high d-excess values, derived from northerly air masses transported from the Arctic Ocean and/or its marginal seas, highlighting key emergent oceanic moisture sources as sea ice cover declines. Resolving these processes across broader spatial-temporal scales is an ongoing research priority, and will be key to quantifying the past, present, and future feedbacks of an amplified Arctic water cycle on the global climate system.

BackgroundCytomegalovirus (CMV) infection is amongst the most important factors complicating solid organ transplantation. In a large prospective randomized clinical trial, valganciclovir prophylaxis reduced the occurrence of CMV infection and disease compared with preemptive therapy in CMV-positive renal allograft recipients (VIPP study; NCT00372229). Here, we present a subanalysis of the VIPP study, investigating single nucleotide polymorphisms (SNPs) in immune-response-related genes and their association with active CMV infection, CMV disease, graft loss or death, rejection, infections, and leukopenia.MethodsBased on literature research ten SNPs were analyzed for TLR4, three for IFN-γ, six for IL10, nine for IL37, and two for TNF-α. An asymptotic independence test (Cochran-Armitage trend test) was used to examine associations between SNPs and the occurrence of CMV infection or other negative outcomes. Statistical significance was defined as pResultsSNPs were analyzed on 116 blood samples. No associations were found between the analyzed SNPs and the occurrence of CMV infection, rejection and leukopenia in all patients. For IL37 rs2723186, an association with CMV disease (p = 0.0499), for IL10 rs1800872, with graft loss or death (p = 0.0207) and for IL10 rs3024496, with infections (p = 0.0258) was observed in all patients, however did not hold true after correction for multiple testing.ConclusionThe study did not reveal significant associations between the analyzed SNPs and the occurrence of negative outcomes in CMV-positive renal transplant recipients after correction for multiple testing. The results of this association analysis may be of use in guiding future research efforts.

Long-term effects of the growing population of HIV-treated people in Southern Africa on individuals and the public health sector at large are not yet understood. This study proposes a novel ‘ratio’ model that relates CD4+ T-cell counts of HIV-infected individuals to the CD4+ count reference values from healthy populations. We use mixed-effects regression to fit the model to data from 1616 children (median age 4.3 years at ART initiation) and 14,542 adults (median age 36 years at ART initiation). We found that the scaled carrying capacity, maximum CD4+ count relative to an HIV-negative individual of similar age, and baseline scaled CD4+ counts were closer to healthy values in children than in adults. Post-ART initiation, CD4+ growth rate was inversely correlated with baseline CD4+ T-cell counts, and consequently higher in adults than children. Our results highlight the impacts of age on dynamics of the immune system of healthy and HIV-infected individuals.

Exercise, including winter sport activities, shows positive effects on physical and mental health, with additional benefits when participating in natural environments. Winter sport activities are particularly vulnerable to climate change, since global warming will decrease the duration and amount of snow. In the context of climate change in alpine environments, little is known on the determinants of winter sport behavior. Thus, the following study primarily aimed at comparing the effect of being exposed to a climate change affected scenario (CCA) or to a climate change unaffected scenario (CCU) on the intention to engage in recreational winter sport activities. Secondly, we aimed to analyze the role of anticipated affective responses during exercising based on the Theory of Planned Behavior (TPB). An experimental cross-sectional web-based study design was used. Participants were randomly allocated to pictures of either CCA or CCU. TPB variables and affective responses with regard to the displayed scenarios were assessed. Statistical analyses included Mann-Whitney-U Tests, linear regression, and mediation analyses. Significant group differences were seen in all TPB variables, p < 0.038; −0.13 < r < −0.30, as well as in affective responses, p < 0.001; −0.24 < r < −0.85. Lower intention to engage in winter sport activities and lower anticipated affective valence during exercising was found in CCA compared to CCU. Attitude toward winter sport was significantly positively associated with intention to engage in winter sport, beta = 0.66, p < 0.001. The effect of group allocation on attitude was mediated by anticipated affective valence, indirect effect = 0.37, p < 0.001. Intention to engage in recreational winter sport activities was lower in participants exposed to the climate change affected winter sport scenario. Since affective valence seems to influence attitude and consequently intention to exercise, the role of non-cognitive variables with regard to climate change related exposure should be considered in future studies. Therefore, winter sport resorts may consider altered winter sport behaviors due to the consequences of climate change as well as the importance of providing an optimal framework to enhance affective valence of their guests in order to mitigate potential changes in winter sports behavior.

An efficient synthesis of a series of pyridazino[4,3-c:5,6-c′]diquinolines was achieved via the autoxidation of 4-hydrazinylquinolin-2(1H)-ones. IR, NMR (1H and 13C), mass spectral data, and elemental analysis were used to fit and elucidate the structures of the newly synthesized compounds. X-ray structure analysis and theoretical calculations unequivocally proved the formation of the structure. The possible mechanism for the reaction is also discussed.

The present study aims to discover novel derivatives as antiapoptotic agents and their protective effects against renal ischemia/reperfusion. Therefore, a series of new thiadiazole analogues 2a–g was designed and synthesized through cyclization of the corresponding opened hydrazinecarbothioamides 1a–g, followed by confirmation of the structure via spectroscopic tools (NMR, IR and mass spectra) and elemental analyses. The antiapoptotic activity showed alongside decreasing of tissue damage induced by I/R in the kidneys of rats using N-acetylcysteine (NAC) as an antiapoptotic reference. Most of the cyclized thiadiazoles are better antiapoptotic agents than their corresponding opened precursors. Particularly, compounds 2c and 2g were the most active antiapoptotic compounds with significant biomarkers. A preliminary mechanistic study was performed through caspase-3 inhibition. Compound 2c was selected along with its corresponding opened precursor 1c. An assay of cytochrome C revealed that there is an attenuation of cytochrome C level of about 5.5-fold, which was better than 1c with a level of 4.1-fold. In caspases-3, 8 and 9 assays, compound 2c showed more potency and selectivity toward caspase-3 and 9 compared with 1c. The renal histopathological investigation indicated normal renal tissue for most of the compounds, especially 2c and 2g, relative to the control. Finally, a molecular docking study was conducted at the caspase-3 active site to suggest possible binding modes.

The synthesis of highly substituted hydroanthraquinone derivatives with up to three stereogenic centres via a Diels–Alder reaction, starting from easily accessible 2-substituted naphthoquinones, is described. The [4+2]-cycloaddition is applicable for a broad range of substrates, runs under mild conditions and results in high yields. The highly regioselective outcome of the reactions is enabled by a benzoyl substituent at C2 of the dienophiles. The obtained hydroanthraquinones can be further modified and represent ideal substrates for follow-up intramolecular coupling reactions to create unique bicyclo[3.3.1] or -[3.2.2]nonane ring systems which are important natural product skeletons.

Six luminophores bearing an OBO-fused benzo[fg]tetracene core as an electron acceptor were designed and synthesized. The molecular structures of three molecules (PXZ-OBO, 5PXZ-OBO, 5DMAC-OBO) were determined by single crystal X-ray diffraction studies and revealed significant torsion between the donor moieties and the OBO acceptor with dihedral angles between 75.5 and 86.2°. Photophysical studies demonstrate that blue and deep blue emission can be realized with photoluminescence maxima (λPL) ranging from 415 to 480 nm in mCP films. The emission energy is modulated by simply varying the strength of the donor heterocycle, the number of donors, and their position relative to the acceptor. Although the DMAC derivatives show negligible delayed emission because of their large singlet-triplet excited state energy difference, ΔEST, PXZ-based molecules, especially PXZ-OBO with an experimental ΔEST of 0.25 eV, demonstrate delayed emission in blend mCP films at room temperature, which suggests triplet exciton harvesting occurs in these samples, potentially by thermally activated delayed fluorescence.

Delayed graft function (DGF) occurs in a significant proportion of deceased donor kidney transplant recipients and was associated with graft injury and inferior clinical outcome. The aim of the present multi-center study was to identify the immunological and non-immunological predictors of DGF and to determine its influence on outcome in the presence and absence of human leukocyte antigen (HLA) antibodies. 1,724 patients who received a deceased donor kidney transplant during 2008–2017 and on whom a pre-transplant serum sample was available were studied. Graft survival during the first 3 post-transplant years was analyzed by multivariable Cox regression. Pre-transplant predictors of DGF and influence of DGF and pre-transplant HLA antibodies on biopsy-proven rejections in the first 3 post-transplant months were determined by multivariable logistic regression. Donor age ≥50 years, simultaneous pre-transplant presence of HLA class I and II antibodies, diabetes mellitus as cause of end-stage renal disease, cold ischemia time ≥18 h, and time on dialysis >5 years were associated with increased risk of DGF, while the risk was reduced if gender of donor or recipient was female or the reason for death of donor was trauma. DGF alone doubled the risk for graft loss, more due to impaired death-censored graft than patient survival. In DGF patients, the risk of death-censored graft loss increased further if HLA antibodies (hazard ratio HR=4.75, P < 0.001) or donor-specific HLA antibodies (DSA, HR=7.39, P < 0.001) were present pre-transplant. In the presence of HLA antibodies or DSA, the incidence of biopsy-proven rejections, including antibody-mediated rejections, increased significantly in patients with as well as without DGF. Recipients without DGF and without biopsy-proven rejections during the first 3 months had the highest fraction of patients with good kidney function at year 1, whereas patients with both DGF and rejection showed the lowest rate of good kidney function, especially when organs from ≥65-year-old donors were used. In this new era of transplantation, besides non-immunological factors, also the pre-transplant presence of HLA class I and II antibodies increase the risk of DGF. Measures to prevent the strong negative impact of DGF on outcome are necessary, especially during organ allocation for presensitized patients.

Background: Typically, African healthcare providers use immunological reference intervals adopted from Europe and the United States (US). This may be inappropriate in a setting with many differences including exposure to different environmental stimuli and pathogens. We compared immunological reference intervals for children from Europe and the US with South African children to explore whether healthy children living in settings with high rates of infectious diseases have different baseline immunological parameters.Methodology: Blood was taken from 381 HIV-uninfected children aged between 2 weeks and 13 years of age from a Child Wellness Clinic in an informal settlement in Cape Town to establish local hematological and lymphocyte reference intervals for South African children. Flow-cytometry quantified percentage and absolute counts of the B-cells, NK-cells, and T-cells including activated, naïve, and memory subsets. These parameters were compared to three separate studies of healthy children in Europe and the US.Results: Increased activated T-cells, and natural killer cells were seen in the younger age-groups. The main finding across all age-groups was that the ratio of naïve/memory CD4 and CD8 T-cells reached a 1:1 ratio around the first decade of life in healthy South African children, far earlier than in resource-rich countries, where it occurs around the fourth decade of life.Conclusions: This is the largest data set to date describing healthy children from an African environment. These data have been used to create local reference intervals for South African children. The dramatic decline in the naïve/memory ratio of both CD4 and CD8 T-cells alongside increased activation markers may indicate that South African children are exposed to a wider range of environmental pathogens in early life than in resource-rich countries. These marked differences illustrate that reference intervals should be relevant to the population they serve. The implications for the developing pediatric immune system requires further investigation.

[This corrects the article DOI: 10.1371/journal.pone.0224723.].

Achievement goals have been a major topic of research for more than 30 years. Achievement goals represent what and why individuals want to achieve. This literature has provided a large body of research in many domains (e.g., education, sports, work), but no study has hitherto been conducted in the driving domain. Moreover, no scale was available to assess achievement goals in driving even though driving is an achievement context. Indeed, drivers' personal competence is engaged and continuously evaluated both by others and the drivers themselves. The present study seeks to fill these gaps. The aims of the study were to emphasize the interest of investigating achievement goals in car driving, to develop and validate a scale named Achievement Goal Questionnaire in Driving (AGQ-D), to compare this baseline model with five alternative models, to assess the gender invariance of the scale, and to study its concurrent validity using interest and self-efficacy in driving, accidents, at-fault accidents, emergency maneuvers, and fines. The results of the Confirmatory Factor Analysis showed the good psychometric properties of the scale completed by 420 French car drivers, in comparison with five alternative models. The scale was also invariant across gender. Finally, the results of the hierarchical regression analyses showed its concurrent validity. The most significant results highlighted that mastery-avoidance goals (i.e., to avoid being a bad driver and avoiding failing in driving task demands) negatively predicted self-reported accidents and at-fault accidents. Performance-approach goals (i.e., to outperform other drivers) also positively predicted self-reported emergency maneuvers. The AGQ-D is now a tool available to develop research in the driving domain and to extend the numerous advances already found in other domains.

This manuscript summarizes recent results on the development of composite luminescent materials based on the single-crystalline films and single crystals of simple and mixed garnet compounds obtained by the liquid-phase epitaxy growth method. Such composite materials can be applied as scintillating and thermoluminescent (TL) detectors for radiation monitoring of mixed ionization fluxes, as well as scintillation screens in the microimaging techniques. The film and crystal parts of composite detectors were fabricated from efficient scintillation/TL materials based on Ce3+-, Pr3+-, and Sc3+-doped Lu3Al5O12 garnets, as well as Ce3+-doped Gd3−xAxAl5−yGayO12 mixed garnets, where A = Lu or Tb; x = 0–1; y = 2–3 with significantly different scintillation decay or positions of the main peaks in their TL glow curves. This work also summarizes the results of optical study of films, crystals, and epitaxial structures of these garnet compounds using absorption, cathodoluminescence, and photoluminescence. The scintillation and TL properties of the developed materials under α- and β-particles and γ-quanta excitations were studied as well. The most efficient variants of the composite scintillation and TL detectors for monitoring of composition of mixed beams of ionizing radiation were selected based on the results of this complex study.

Several reports indicated that a large proportion of dairy cows have not resumed cyclicity until day 60 after calving. These cows are traditionally classified as non-cycling (anoestrous or anovular cows). Static ovaries (SO, lack of luteal tissue and follicles >8 mm, and progesterone < 0.5 ng/mL) could be a possible underlying reason that contributes to a non-cycling status. Although SO affects both primiparous (PP) and multiparous (MP) cows, PP cows are more prone to be non-cycling than MP. Therefore, this study aims to compare the metabolic profiles and hormonal status between non-cycling PP and MP cows diagnosed with SO. One hundred and twenty one animals that did not express signs of oestrus until day 60 postpartum were grouped by parity (PP, n=58 and MP, n=63), then blood sampled and examined using transrectal ultrasonography. Blood samples were collected before the ultrasonographic examination. Out of those, 42 PP (72.4%) and 28 MP (44.4%) were diagnosed as non-cycling (bearing SO). Serum concentrations of triglycerides, cholesterol, total protein and albumin did not differ between parity groups. The glucose concentrations in PP cows (1.43 ± 0.59 mmol/L) and MP cows (1.69 ± 0.71 mmol/L) did not differ, however, they were less than the normal physiological concentration. In addition, no differences were detected between parity groups for concentrations of NEFA, β-HBA, progesterone and estradiol. In summary, we concluded that non-cycling PP and MP cows bearing SO have similar hormonal status and metabolic profiles.

Abstract Background Accurate assessment of health-related quality of life as an endpoint in intervention studies is a major challenge in dementia research. The DEMQOL (29 items) and the proxy version (32 items), which is partly based on the DEMQOL, are internationally used instruments. To date, there is no information on the structural validity, item distribution, or internal consistency for the German language version of these questionnaires. Methods This psychometric study is based on a secondary data analysis of a sample of 201 outpatients with a mild form of Alzheimer’s disease (AD) and their informal caregivers. The informal caregivers who were interviewed were involved in the care of the person with AD several times per week. The analysis for the evaluation of the structural validity was performed using Mokken scale analysis. The internal consistency was calculated using the ρ of the Molenaar Sijtsma statistic and Cronbach’s α. Results For both versions, four subscales were identified: [A] “positive emotions”, [B] “negative emotions”, [C] “physical and cognitive functioning”, and [D] “daily activities and social relationships”. For both instruments, the internal consistency of all subscales was considered “good” (ρ = 0.71–0.88, α = 0.72–0.87). Conclusions The results are a first indication of good construct validity of the instruments used for the German setting. We recommend further investigations of the test-retest reliability and the inter-rater reliability of the proxy instrument.

Implementation of an e-participation system in a low-income region with poor infrastructure, limited access to ICT and low awareness of civic rights and responsibilities, is challenging and requires thorough understanding of the contextual conditions and requirements. Present study provides a qualitative analysis of the implementation phase of an e-participation platform mapping the specific factors that play key roles in defining the access to and the use of the system by the citizens. Social and political context as well as the design and management of the platform are found to be the two crucial dimensions defining successful use of a platform.

Abstract Background The Quality of Life in Alzheimer’s disease scale (QoL-AD) is a widely used Health Related Quality of Life (HRQoL) instrument. However, studies investigating the instrument’s inter-rater reliability (IRR) are missing. This study aimed to determine the item distribution and IRR of the German proxy version of the QoL-AD (13 Items) and a nursing home-specific instrument version (QoL-AD NH, 15 Items). Methods The instruments were applied to 73 people with dementia living in eight nursing homes in Germany. Individuals with dementia were assessed two times by blinded proxy raters. The IRR analyses were based on methodological criteria of the quality appraisal tool for studies of diagnostic reliability (QAREL), the COSMIN group and the single-measure Intra-Class Correlation Coefficient (ICC) for absolute agreement ≥0.70. Results All items for both instrument versions demonstrated acceptable item difficulty, with the exception of one item (QoL-AD proxy). The IRR was moderate for the QoL-AD (ICC: 0.65) and insufficient for the QoL-AD NH (ICC: 0.18). The additional computation of the average measure ICC for two proxy-raters demonstrated a strong IRR (ICC: 0.79) for the QoL-AD and a weak IRR for the QoL-AD NH (ICC: 0.31). The detailed analysis of the IRR for each item underpinned the need for the further development of both instruments. Conclusions The unsatisfactory IRRs for both instruments highlight the need for the development of a user guide including general instructions for instrument application as well as definitions and examples reflecting item meaning. Priority should be given to the development of reliable proxy-person versions of both instruments. Trial registration ClinicalTrials.gov: NCT02295462, Date of registration: 11–20-2014.

The sensitization of scintillation was investigated in crosslinked polymeric composite materials loaded with luminescent gold clusters aggregates acting as sensitizers, and with organic dye rhodamine 6G as the emitting species. The evolution in time of the excited states population in the systems is described by a set of coupled rate equations, in which steady state solution allowed obtainment of an expression of the sensitization efficacy as a function of the characteristic parameters of the employed luminescent systems. The results obtained indicate that the realization of sensitizer/emitter scintillating complexes is the strategy that must be pursued to maximize the sensitization effect in composite materials.

The development of efficient biomass valorization is imperative for the future sustainable production of chemicals and fuels. Particularly, the last decade has witnessed the development of a plethora of effective and selective transformations of bio-based furanics using homogeneous organometallic catalysis under mild conditions. In this review, we describe some of the advances regarding the conversion of target furanics into value chemicals, monomers for high-performance polymers and materials, and pharmaceutical key intermediates using homogeneous catalysis. Finally, the incorporation of furanic skeletons into complex chemical architectures by multifunctionalization routes is also described.

Cisplatin (cisPt) is an important drug that is used against various cancers, including advanced lung cancer. However, drug resistance is still a major ongoing problem and its investigation is of paramount interest. Here, a high-resolution magic angle spinning (HR-MAS) NMR study is presented deciphering the metabolic profile of non-small cell lung cancer (NSCLC) cells and metabolic adaptations at different levels of induced cisPt-resistance, as well as in their de-induced counterparts (cells cultivated in absence of cisPt). In total, fifty-three metabolites were identified and quantified in the 1H-HR-MAS NMR cell spectra. Metabolic adaptations to cisPt-resistance were detected, which correlated with the degree of resistance. Importantly, de-induced cell lines demonstrated similar metabolic adaptations as the corresponding cisPt-resistant cell lines. Metabolites predominantly changed in cisPt resistant cells and their de-induced counterparts include glutathione and taurine. Characteristic metabolic patterns for cisPt resistance may become relevant as biomarkers in cancer medicine.

Platinum compounds such as cisplatin (cisPt) embody the backbone of combination chemotherapy protocols against advanced lung cancer. However, their efficacy is primarily limited by inherent or acquired platinum resistance, the origin of which has not been fully elucidated yet, although of paramount interest. Using single cell inductively coupled plasma mass spectrometry (SC-ICP-MS), this study quantifies cisPt in single cancer cells and for the first time in isolated nuclei. A comparison of cisPt uptake was performed between a wild type (wt) cancer cell line and related resistant sublines. In both, resistant cells, wt cells, and their nuclei, cisPt uptake was measured at different incubation times. A lower amount of cisPt was found in resistant cell lines and their nuclei compared to wt cells. Moreover, the abundance of internalized cisPt decreased with increasing resistance. Interestingly, concentrations of cisPt found within the nuclei were higher than compared to cellular concentrations. Here, we show, that SC-ICP-MS allows precise and accurate quantification of metallodrugs in both single cells and cell organelles such as nuclei. These findings pave the way for future applications investigating the potency and efficacy of novel metallodrugs developed for cancer treatment.

In view of the deliberations on new Euro 7 emission standards to be introduced by 2025, original equipment manufacturers (OEMs) are already hard at work to further minimise the pollutant emissions of their vehicles. A particular challenge in this context will be compliance with new particulate number (PN) limits. It is expected that these will be tightened significantly, especially by including particulates down to 10 nm. This will lead to a substantially increased effort in the calibration of gasoline particulate filter (GPF) control systems. Therefore, it is of great interest to implement advanced methods that enable shortened and at the same time more accurate GPF calibration techniques. In this context, this study presents an innovative GPF calibration procedure that can enable a uniquely efficient development process. In doing so, some calibration work packages involving GPF soot loading and regeneration are transferred to a modern burner test bench. This approach can minimise the costly and time-consuming use of engine test benches for GPF calibration tasks. Accurate characterisation of the particulate emissions produced after a cold start by the target engine in terms of size distribution, morphology, and the following exhaust gas backpressure and burn-off rates of the soot inside the GPF provides the basis for a precise reproduction and validation process on the burner test bench. The burner test bench presented enables the generation of particulates with a geometric mean diameter (GMD) of 35 nm, exactly as they were measured in the exhaust gas of the engine. The elemental composition of the burner particulates also shows strong similarities to the particulates produced by the gasoline engine, which is further confirmed by matching burn-off rates. Furthermore, the exhaust backpressure behaviour can accurately be reproduced over the entire loading range of the GPF. By shifting GPF-related calibration tasks to the burner test bench, total filter loading times can be reduced by up to 93%.

Outstanding affinity and specificity are the main characteristics of peptides, rendering them interesting compounds for basic and medicinal research. However, their biological applicability is limited due to fast proteolytic degradation. The use of mimetic peptoids overcomes this disadvantage, though they lack stereochemical information at the α-carbon. Hybrids composed of amino acids and peptoid monomers combine the unique properties of both parent classes. Rigidification of the backbone increases the affinity towards various targets. However, only little is known about the spatial structure of such constrained hybrids. The determination of the three-dimensional structure is a key step for the identification of new targets as well as the rational design of bioactive compounds. Herein, we report the synthesis and the structural elucidation of novel tetrameric macrocycles. Measurements were taken in solid and solution states with the help of X-ray scattering and NMR spectroscopy. The investigations made will help to find diverse applications for this new, promising compound class.

CsPbBr3 nanocrystals have been identified as a highly promising material for various optoelectronic applications. However, they tend to coexist with Cs4PbBr6 phase when the reaction conditions are not controlled carefully. It is therefore imperative to understand how the presence of this phase affects the luminescence performance of CsPbBr3 nanocrystals. We synthesized a mixed CsPbBr3-Cs4PbBr6 sample, and compared its photo- and radioluminescence properties, including timing characteristics, to the performance of pure CsPbBr3 nanocrystals. The possibility of energy transfer between the two phases was also explored. We demonstrated that the presence of Cs4PbBr6 causes significant drop in radioluminescence intensity of CsPbBr3 nanocrystals, which can limit possible future applications of Cs4PbBr6-CsPbBr3 mixtures or composites as scintillation detectors.

The scintillation properties of novel type of composite scintillator based on Lu3Al5O12:Pr (LuAG:Pr) single crystalline film (SCF) and LuAG:Sc substrate grown by the liquid-phase epitaxy method are considered in this work. The registration of α-particles and γ-quanta in such types of composites occurs by means of separation of the scintillation decay kinetics of SCF and crystal parts, respectively. Namely, under excitation by α-particles of 241Am (5.5 MeV) source and γ-quanta of 137Cs (662 keV) source, the large differences in the respective scintillation decay kinetics and decay time values tα and tγ are observed for the LuAG:Pr SCF/LuAG:Sc SC composite scintillator with various film thicknesses. Furthermore, the best tγ/tα ratio above 4.5 is achieved for such types of epitaxial structure with SCF and substrate thicknesses of 17 μm and about 0.5 mm, respectively. The development types of composite scintillators can be successfully applied for simultaneous registration of α-particles and γ-quanta in the mixed radiation fluxes.

Abstract Background Caring for people with dementia at home requires a significant amount of time, organization, and commitment. Therefore, informal caregivers, mainly relatives, of people with dementia often feel a high burden. Although on-site support groups are known to have positive effects on the subjective well-being (SWB) and perceived social support of informal caregivers, there are cases in which relatives have either no time or no opportunity to leave the person alone or in which there are no support groups nearby. The TALKING TIME project aims to close this supply gap by providing structured telephone-based support groups in Germany for the first time. International studies have shown benefits for informal caregivers. Methods The TALKING TIME study is a randomized controlled trial. The effects of the 3-month TALKING TIME intervention will be compared with those of a control group without intervention at two time points (baseline = T0, after 3 months = T1). The control group will receive the TALKING TIME intervention after T1. With a planned sample size of 88 participants, the study is powered to detect an estimated effect size of 0.70 for psychological quality of life, considering an α of 0.05 (two-sided), a power of 80%. Caregivers are informal caregivers who are eligible if they are 18 years of age or older and have cared for a person with diagnosed dementia for at least four hours, four days per week, in the past six months. The exclusion criteria are psychiatric disorders of the informal caregiver. The primary outcome is the mental component summary of the SF-12 rated by informal caregivers. The secondary outcomes for informal caregivers are the physical component summary of the SF-12, the Perceived Social Support Caregiver Scale (SSCS) score, and the Caregiver Reaction Scale (CRS) score. The secondary outcome for care recipients is the Neuropsychiatric Inventory (NPI-Q). For the process evaluation, different quantitative and qualitative data sources will be collected to address reach, fidelity, dosage and context. Discussion The results will provide further information on the effectiveness and optimization of telephone-based support groups for informal caregivers of people with dementia, which can help guide the further development of effective telephone-based social support group interventions. Trial registration Clinical Trials: NCT02806583 , June 9, 2016

The mesomeric betaine imidazolium-1-ylphenolate forms a borane adduct with tris(pentafluorophenyl)borane by coordination with the phenolate oxygen, whereas its NHC tautomer 1-(2-phenol)imidazol-2-ylidene reacts with (triphenylphosphine)gold(I) chloride to give the cationic NHC complex [Au(NHC)2][Cl] by coordination with the carbene carbon atom. The anionic N-heterocyclic carbene 1-(2-phenolate)imidazol-2-ylidene gives the complexes [K][Au(NHC−)2], [Rh(NHC−)3] and [Ni(NHC−)2], respectively. Results of four single crystal analyses are presented.

Para la aprobación, registro y comercialización de medicamentos, agroquímicos, productos de uso doméstico y sustancias cosméticas es necesario estudiar e informar al organismo regulador la potencial toxicidad. Por motivos éticos y económicos, en los últimos años se ha disminuido la utilización de animales de experimentación y se ha fomentado el desarrollo de metodologías alternativas. En el proceso de migración, la OCDE validó procedimientos para evaluar irritación y corrosión ocular y dérmica, mutagenicidad, fototoxicidad, sensibilización y absorción dérmica. Hoy en día es un área en constante investigación y desarrollo ya que aún no se ha logrado reemplazar completamente la calidad de los datos obtenidos en animales. Si bien la tendencia mundial al reemplazo de animales es clara, en Argentina aún no hemos dado el primer paso: no contamos con una ley que regule el uso de animales de experimentación. Las agencias reguladoras (SENASA y ANMAT) continúan solicitando ensayos con animales, pero han manifestado su interés en aceptar evidencia toxicológica obtenida por métodos alternativos. Desde el Laboratorio de Métodos Alternativos al uso de Animales de Experimentación que forma parte de la Plataforma Tecnológica EBAL nos hemos propuesto trabajar en el desarrollo, ejecución, perfeccionamiento y transferencia de metodología alternativa.

Microbial biofilms are the cause of persistent infections associated with various medical implants and distinct body sites such as the urinary tract, lungs, and wounds. Compared with their free living counterparts, bacteria in biofilms display a highly increased resistance to immune system activities and antibiotic treatment. Therefore, biofilm infections are difficult or impossible to treat with our current armory of antibiotics. The challenges associated with biofilm infections have urged researchers to pursue a better understanding of the molecular mechanisms that are involved in the formation and dispersal of biofilms, and this has led to the identification of several steps that could be targeted in order to eradicate these challenging infections. Here we describe mechanisms that are involved in the regulation of biofilm development in Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii, and provide examples of chemical compounds that have been developed to specifically inhibit these processes. These compounds include (i) pilicides and curlicides which inhibit the initial steps of biofilm formation by E. coli; (ii) compounds that interfere with c-di-GMP signaling in P. aeruginosa and E. coli; and (iii) compounds that inhibit quorum-sensing in P. aeruginosa and A. baumannii. In cases where compound series have a defined molecular target, we focus on elucidating structure activity relationship (SAR) trends within the particular compound series.

Background: Neuropsychological screening becomes increasingly important for the evaluation of subarachnoid hemorrhage (SAH) and stroke patients. It is often performed during the surveillance period on the intensive (ICU), while it remains unknown, whether the distraction in this environment influences the results. We aimed to study the reliability of the Montreal Cognitive Assessment (MoCA) in the ICU environment.Methods: Consecutive stable patients with recent brain injury (tumor, trauma, stroke, etc.) were evaluated twice within 36 h using official parallel versions of the MoCA (ΔMoCA). The sequence of assessment was randomized into (a) busy ICU first or (b) quiet office first with subsequent crossover. For repeated MoCA, we determined sequence, period, location effects, and the intraclass correlation coefficient (ICC).Results:N = 50 patients were studied [n = 30 (60%) male], with a mean age of 57 years. The assessment's sequence [“ICU first” mean ΔMoCA −1.14 (SD 2.34) vs. “Office first” −0.73 (SD 1.52)] did not influence the MoCA (p = 0.47). On the 2nd period, participants scored 0.96 points worse (SD 2.01; p = 0.001), indicating no MoCA learning effect but a possible difference in parallel versions. There was no location effect (p = 0.31) with ΔMoCA between locations (Office minus ICU) of −0.32 (SD 2.21). The ICC for repeated MoCA was 0.87 (95% CI 0.79–0.92).Conclusions: The reliability of the MoCA was excellent, independent from the testing environment being ICU or office. This finding is helpful for patient care and studies investigating the effect of a therapeutic intervention on the neuropsychological outcome after SAH, stroke or traumatic brain injury.

Massively parallel DNA sequencing opens up opportunities for bridging multiple temporal and spatial dimensions in biodiversity research, thanks to its efficiency to recover millions of nucleotide polymorphisms. Here, we identify the current status, discuss the main challenges, and look into future perspectives on biodiversity genomics focusing on insects, which arguably constitute the most diverse and ecologically important group among all animals. We suggest 10 simple rules that provide a succinct step-by-step guide and best-practices to anyone interested in biodiversity research through the study of insect genomics. To this end, we review relevant literature on biodiversity and evolutionary research in the field of entomology. Our compilation is targeted at researchers and students who may not yet be specialists in entomology or molecular biology. We foresee that the genomic revolution and its application to the study of non-model insect lineages will represent a major leap to our understanding of insect diversity.

This paper explores pre-service history teachers' ability to recognize and reflect on typical situations occurring in the history classroom and to link these to students' historical learning. Therefore, we draw on the concept of professional vision (Goodwin, 1994), which assumes that teachers need a professional knowledge base to monitor and to reason about teaching and student learning. Based on theoretical notions of teachers' pedagogical content knowledge (PCK), we investigated history teachers' professional vision by means of a video survey with integrated video clips, open-ended writing assignments and standardized item ratings. We collected data from 303 and 220 pre-service teachers at the beginning and at the end, respectively, of their subject-specific teacher training. The collected data open up the possibility of 'simultaneous triangulation' (Morse, 1991), which was used for test validation. First, we tested the reliability of the closed-ended test instrument using item response theory, in order to develop a feasible test model. Second, we investigated the validity of the test instrument by comparing test results with the findings of the open-ended writing task. In general, student teachers reached rather low test scores. They experienced difficulties in assessing classroom events in terms of their potential to support historical competencies and to evaluate the consequences for students' learning. Findings from the open writing assignment show that student teachers commented largely on generic teaching strategies while hardly noticing student learning. In sum, the chosen methodological approaches seem to contribute to a more distinct picture of preservice teachers' abilities to reason about history teaching and learning.

In vivo and ex vivo sensors have the potential to aid tracking and anti-poaching endeavours and provide new insights into rhinoceros physiology and environment. However, the propagation of electromagnetic signals in rhinoceros tissue is currently not known. We present simulation and agar models of the rhinoceros that allow the investigation of electromagnetic propagation by in vivo and ex vivo devices without the need for surgery. Since the dielectric properties of rhinoceros tissue have not been documented, the conductivity and permittivity of the skin, fat, muscle, blood and other organs are first approximated by means of a meta-analysis that includes animals with similar physical properties. Subsequently, we develop anatomical models that include dermal layers, internal organs and a skeleton. We also develop a flank model that serves as an approximation of the anatomical model in certain situations. These models are used to determine the viability of communication between an in vivo device and an ex vivo device attached to the hind leg of the animal. Two types of antenna (microstrip-fed planar elliptical monopole antenna and printed inverted-F antenna) and three feasible implant locations (back, neck and chest) are considered. In addition to the computer models, phantom recipes using salt, sugar and agar are developed to match the dielectric properties of each tissue type at the industrial, scientific and medical (ISM) frequencies of 403MHz, 910MHz and 2.4GHz. The average error between the measured and theoretically predicted dielectric values was 6.22% over all recipes and 4.49% for the 2.4 GHz recipe specifically. When considering the predicted efficiency of the transmitting and receiving antennas, an agreement of 67.38% was demonstrated between the computer simulations and laboratory measurements using the agar rhinoceros flank models. Computer simulations using the anatomical model of the rhinoceros indicate that the chest is the optimal implant location and that best signal propagation is achieved using the planar inverted-F antenna (PIFA). Using this configuration, the simulations indicate that communication between the implant and an ex vivo device attached to the hind leg is challenging but possible. Furthermore, we find that the inclusion of factors such as the density and temperature of the phantom materials were found to be critical to the achievement of good agreement between practice and simulation.

INTRODUCTION:There are Challenges in statistically modelling immune responses to longitudinal HIV viral load exposure as a function of covariates. We define Bayesian Markov Chain Monte Carlo mixed effects models to incorporate priors and examine the effect of different distributional assumptions. We prospectively fit these models to an as-yet-unpublished data from the Tshwane District Hospital HIV treatment clinic in South Africa, to determine if cumulative log viral load, an indicator of long-term viral exposure, is a valid predictor of immune response. METHODS:Models are defined, to express 'slope', i.e. mean annual increase in CD4 counts, and 'asymptote', i.e. the odds of having a CD4 count ≥500 cells/μL during antiretroviral treatment, as a function of covariates and random-effects. We compare the effect of using informative versus non-informative prior distributions on model parameters. Models with cubic splines or Skew-normal distributions are also compared using the conditional Deviance Information Criterion. RESULTS:The data of 750 patients are analyzed. Overall, models adjusting for cumulative log viral load provide a significantly better fit than those that do not. An increase in cumulative log viral load is associated with a decrease in CD4 count slope (19.6 cells/μL (95% credible interval: 28.26, 10.93)) and a reduction in the odds of achieving a CD4 counts ≥500 cells/μL (0.42 (95% CI: 0.236, 0.730)) during 5 years of therapy. Using informative priors improves the cumulative log viral load estimate, and a skew-normal distribution for the random-intercept and measurement error results is a better fit compared to using classical Gaussian distributions. DISCUSSION:We demonstrate in an unpublished South African cohort that cumulative log viral load is a strong and significant predictor of both CD4 count slope and asymptote. We argue that Bayesian methods should be used more frequently for such data, given their flexibility to incorporate prior information and non-Gaussian distributions.

Recent developments in medical imaging techniques, in particular, those in time-of-flight positron emission tomography put new challenges on scintillating material performance that cannot be fulfilled by conventional scintillators. Bright and ultrafast nanoparticles represent promising candidates to build up an advanced detection system needed. We synthesize colloidal CsPbBr3 nanoplatelets emitting blue light with fast sub-nanosecond decay. We also prepare a nanocomposite material by embedding the nanoplatelets in the polystyrene matrix. We show that blue emission is preserved provided the composite is not exposed to UV/vis light and/or elevated temperatures. Motivated by conflicting information from the literature about the room temperature structure of colloidal CsPbX3 (X = Cl, Br, I) particles, that results being orthorhombic, rather than cubic, we perform ab initio electronic structure calculations of bulk crystals with an orthorhombic structure. We calculate optical properties, as well as exciton diameters and binding energies and compare them to those previously obtained for cubic CsPbX3 crystals.

We report the first example of employing homogeneous organometal-catalyzed transfer hydrogenation for the selective reductive amination of furfurals to furfurylamines. An efficient, chemoselective, and base-free method is described using Ru-MACHO-BH as catalyst and iPrOH as H donor. The method tolerates a range of substituents affording moderate to excellent yields.

Peptoids, or poly-N-substituted glycines, are characterised by broad structural diversity. Compared to peptides, they are less restricted in rotation and lack backbone-derived H bonding. Nevertheless, certain side chains force the peptoid backbone into distinct conformations. Designable secondary structures like helices or nanosheets arise from this knowledge. Herein, we report the copper-catalysed alkyne-azide cycloaddition (CuAAC) of macrocycles to form innovative tube-like tricyclic peptoids, giving access to host–guest chemistry or storage applications. Different linker systems make the single tubes tuneable in size and enable modifications within the gap. An azobenzene linker, which is reversibly switchable in conformation, was successfully incorporated and allowed for light-triggered changes of the entire tricyclic structure.