Dimethyl fumarate treatment in relapsed and refractory cutaneous T-cell lymphoma: a multicenter phase 2 study.

Targeted therapies for cutaneous T-cell lymphoma (CTCL) are limited and curative approaches are lacking. Furthermore, relapses and drug induced side effects are major challenges in the therapeutic management of patients with CTCL, creating an urgent need for new and effective therapies. Pathologic constitutive NF-κB activity leads to apoptosis resistance in CTCL cells and, thus, represents a promising therapeutic target in CTCL. In a preclinical study we showed the potential of dimethyl fumarate (DMF) to block NF-κB and, specifically, kill CTCL cells. To translate these findings to applications in a clinical setting, we performed a multicentric phase 2 study evaluating oral DMF therapy in 25 patients with CTCL stages Ib to IV over 24 weeks (EudraCT number 2014-000924-11/NCT number NCT02546440). End points were safety and efficacy. We evaluated skin involvement (using a modified severity weighted assessment tool [mSWAT]), pruritus, quality of life, and blood involvement, if applicable, as well as translational data. Upon skin analysis, 7 of 23 (30.4%) patients showed a response with >50% reduction in the mSWAT score. Patients with high tumor burden in the skin and blood responded best to DMF therapy. Although not generally significant, DMF also improved pruritus in several patients. Response in the blood was mixed, but we confirmed the NF-κB-inhibiting mechanism of DMF in the blood. The overall tolerability of the DMF therapy was very favorable, with mostly mild side effects. In conclusion, our study presents DMF as an effective and excellently tolerable therapeutic option in CTCL to be further evaluated in a phase 3 study or real-life patient care as well as in combination therapies. This trial was registered at www.clinicaltrials.gov as #NCT02546440.

Deep immune profiling of chronic rhinosinusitis in allergic and non-allergic cohorts using mass cytometry.

Chronic rhinosinusitis (CRS) is a persistent nasal and paranasal sinus mucosa inflammation comprising two phenotypes, namely CRS with nasal polyps (CRSwNP) and without (CRSsNP). CRSwNP can be associated with asthma and hypersensitivity to non-steroidal anti-inflammatory drug (NSAID) in a syndrome known as NSAID-exacerbated respiratory disease (N-ERD). Furthermore, CRS frequently intertwines with respiratory allergies. This study investigated levels of 33 different nasal and serum cytokines and phenotypic characteristics of peripheral blood mononuclear cells (PBMCs) within cohorts of CRS patients (n = 24), additionally examining the influence of comorbid respiratory allergies by mass cytometry. N-ERD patients showed heightened type 2 nasal cytokine levels. Mass cytometry revealed increased activated naive B cell levels in CRSwNP and N-ERD, while resting naive B cells were higher in CRSsNP. Th2a cell levels were significantly elevated in allergic subjects, but not in CRS groups. In conclusion, there are distinct immunological features in PBMCs of CRS phenotypes and allergy.

The role of sociodemographic, psychosocial, and behavioral factors in the use of preventive healthcare services in children and adolescents: results of the KiGGS Wave 2 study.

BACKGROUND: In Germany, various preventive services are offered to children and adolescents. These include regular standardized examinations (so called U/J examinations) and several vaccinations. Although strongly recommended, most of them are not mandatory. Our aim is to identify factors associated with the use of U/J examinations and vaccination against diphtheria, hepatitis B, Hib, pertussis, polio, and tetanus. While previous research has focused on sociodemographic factors, we also include socioeconomic, behavioral, and psychosocial factors. METHODS: We analyzed cross-sectional data from 15,023 participants (aged 0-17 years) of the nationwide representative KiGGS Wave 2 Survey. Participation in U/J examinations was assessed using a questionnaire, filled out by participants and/or their parents. Information on vaccination status was drawn from the participants' vaccination booklets. To identify relevant determinants for the use of preventive examinations and vaccinations, unadjusted and adjusted logistic regression models were employed with up to 16 different independent variables. RESULTS: Various independent variables showed an association with the use of preventive services. Higher socioeconomic status, absence of migration background, and lower household size were associated with significantly higher utilization of U examinations. Parents' marital status, area of residence, behavioral and psychosocial factors yielded insignificant results for most U/J examinations. Higher vaccination rates were found for children with no migration background, with residence in eastern Germany, lower household size, and with married parents. CONCLUSION: This study attempted to depict the influence of sociodemographic, psychosocial, and behavioral factors on the use of several preventive services. Our results indicate that predominantly sociodemographic variables influence the use of preventive services. Further efforts should be made to investigate the interplay of different determinants of healthcare use in children and adolescents.

Understanding e-Cigarette Addictiveness: Triangulation of Focus Group and Netnographic Data.

BACKGROUND: Numerous studies have shown that e-cigarettes are addictive. For example, we previously showed that users of e-cigarette online forums discuss experiences of addiction in a netnographic analysis. However, it is unclear what makes e-cigarettes addictive apart from nicotine. In a focus group analysis, we recently identified 3 unique features of e-cigarettes that users linked to experiences of addiction: the pleasant taste, unobtrusiveness, and unlimited usability of e-cigarettes. OBJECTIVE: This study aimed to validate the previously identified features of e-cigarette addictive potential by triangulating data from the netnographic analysis and focus group discussions. METHODS: Drawing on a netnographic analysis of 3 popular, German-language e-cigarette forums, we studied whether experiences of addiction were linked to specific e-cigarette features. We included 451 threads in the analysis that had been coded for addictive experiences in a previous study by our team. First, we conducted a deductive analysis with preregistered codes to determine whether the features of pleasant taste, unobtrusiveness, and unlimited usability were mentioned in relation to the addictive potential of e-cigarettes in the online forums. Second, an inductive approach was chosen to identify further possible addictive features of e-cigarettes. RESULTS: Our deductive analysis confirmed that the features highlighted in our previous focus group study (pleasant taste, unobtrusiveness, and unlimited usability) were also frequently discussed in online forums in connection to addictive symptoms. In addition, our inductive analysis identified nicotine dosage as a significant feature linked to addiction. Users reported varying their nicotine doses for different reasons, leading to the identification of four distinct user types based on dosing patterns: (1) high doses for intermittent, (2) high doses for constant use, (3) low doses for constant use, and (4) switching between high and low doses depending on the situation. CONCLUSIONS: Our comprehensive analysis of online forum threads revealed that users' experiences of addiction are linked to 4 specific features unique to e-cigarettes: pleasant taste, unobtrusiveness, unlimited usability, and nicotine dosage. Recognizing these addictive features of e-cigarettes is crucial for designing cessation programs and informing public health policies to reduce the addictiveness of e-cigarettes.

Nasal IL-13 production identifies patients with late-phase allergic responses.

BACKGROUND: There is limited knowledge on how local cytokine secretion patterns after nasal allergen challenge correlate with clinical symptoms especially with regard to the "late allergic response," which occurs in approximately 40% to 50% of patients with allergy. OBJECTIVE: We sought to characterize the immunologic and clinical nasal responses to birch pollen allergen challenge with a special focus on the late allergic response. METHODS: In this randomized, double-blind, placebo-controlled trial, birch pollen-allergic participants were challenged with birch pollen extract (n = 20) or placebo (n = 10) on 3 consecutive days. On days 1 and 3, nasal secretions were collected at selected time points over a 24-hour time course for the measurement of 33 inflammatory mediators. Clinical responses were determined through subjective symptom scores and objective nasal airflow measurements. RESULTS: Provoked participants had significantly greater clinical responses and showed significant increases in tryptase and the soluble IL-33 receptor serum stimulation 2 (sST2) in nasal secretions within minutes compared with the placebo group. Eight of 20 provoked participants displayed high IL-13 levels 2 to 8 hours after allergen provocation. This group also showed significant changes in clinical parameters, with a secondary drop in nasal airflow measured by peak nasal inspiratory flow and increased symptoms of nasal obstruction, which significantly differed from IL-13 nonresponders after 6 hours. CONCLUSIONS: IL-13 response status correlates with clinical responses and type 2 cytokine responses in the late phase after allergen provocation.

C-H Bond Activation by Iridium(III) and Iridium(IV) Oxo Complexes.

Oxidation of an iridium(III) oxo precursor enabled the structural, spectroscopic, and quantum-chemical characterization of the first well-defined iridium(IV) oxo complex. Side-by-side examination of the proton-coupled electron transfer thermochemistry revealed similar driving forces for the isostructural oxo complexes in two redox states due to compensating contributions from H+ and e- transfer. However, C-H activation of dihydroanthracene revealed significant hydrogen tunneling for the distinctly more basic iridium(III) oxo complex. Our findings complement the growing body of data that relate tunneling to ground state properties as predictors for the selectivity of C-H bond activation.

Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease.

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) comprises the triad of chronic rhinosinusitis with nasal polyps, asthma and intolerance to NSAIDs. Dupilumab treatment, targeting the interleukin-4 (IL-4) receptor α, significantly reduces polyp burden as well as asthma symptoms. Here we aimed to investigate the effect of dupilumab on aspirin intolerance, burden of disease and nasal cytokine profiles in patients with N-ERD. METHODS: In this open-label trial, adult patients with confirmed N-ERD were treated with dupilumab for 6 months. Clinical parameters (e.g. total polyp scores, quality of life questionnaires, smell test, spirometry), oral aspirin provocation testing and blood, nasal and urine sampling were monitored at regular intervals for up to 6 months after starting dupilumab therapy. RESULTS: Of the 31 patients included in the study, 30 completed both aspirin provocation tests. After 6 months of treatment with dupilumab, 23% of patients (n=7 of 30) developed complete aspirin tolerance and an additional 33% of patients (n=10 of 30) tolerated higher doses. Polyp burden was significantly reduced (total polyp score: -2.68±1.84, p<0.001), while pulmonary symptoms (asthma control test: +2.34±3.67, p<0.001) and olfactory performance improved (University of Pennsylvania Smell Identification Test: +11.16±9.54, p<0.001) in all patients after therapy. Patients with increased aspirin tolerance showed a significant decrease in urinary leukotriene E4 levels and their improvement in clinical parameters was associated with a reduction of eotaxin-1, C-C motif chemokine ligand 17, IL-5, IL-17A and IL-6. CONCLUSION: In this study, 57% of N-ERD patients tolerated higher doses of aspirin under dupilumab therapy.

Association of viral load with TRAIL, IP-10, CRP biomarker signature and disease severity in children with respiratory tract infection or fever without source: A prospective, multicentre cohort study.

BACKGROUND: To investigate the association of viral load (VL) with (i) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10, C-reactive protein, and a combinatorial score (BV score), and (ii) clinical severity. STUDY DESIGN: In this prospective, multicentre cohort substudy, children with respiratory tract infection or fever without source were enrolled. VL for influenza virus, rhinovirus, respiratory syncytial virus, and adenovirus was measured from nasopharyngeal swabs. The reference standard diagnosis was established based on expert panel adjudication. RESULTS: Of 1140 recruited patients, 333 had a virus monodetection. VL for the aggregated data set correlated with TRAIL and IP-10 levels, with the length of oxygen therapy, and inversely with the BV score. At a single viral level, only the influenza VL yielded a correlation with TRAIL, IP-10 levels, and the BV score. Children with a viral reference standard diagnosis had significantly higher VL than those with bacterial infection (p = 0.0005). Low TRAIL (incidence rate ratio [IRR] 0.6, 95% confidence interval [CI] 0.39-0.91) and young age (IRR 0.62, 95% CI 0.49-0.79) were associated with a longer hospital stay, while young age (IRR 0.33, 95% CI 0.18-0.61), low TRAIL (IRR 0.25, 95% CI 0.08-0.76), and high VL (IRR 1.16, 95% CI 1.00-1.33) were predictive of longer oxygen therapy. CONCLUSION: These findings indicate that VL correlates with biomarkers and may serve as a complementary tool pertaining to disease severity.

Nitrogen Fixation via Splitting into Nitrido Complexes.

The large carbon footprint of the Haber-Bosch process, which provides ammonia for fertilizers but also the feedstock for all nitrogenous commercial products, has fueled the quest for alternative synthetic strategies to nitrogen fixation. Owing to the extraordinarily strong N≡N triple bond, the key step of the Haber-Bosch reaction, i.e., the dissociative adsorption of N2, requires high temperatures. Since the first report in 1995, a wide variety of molecular transition metal and f-block compounds have been reported that can fully cleave N2 at ambient conditions and form well-defined nitrido complexes. We here provide a comprehensive survey of the current state of N2 splitting reactions in solution and follow-up nitrogen transfer reactivity. Particular emphasis is put on electronic structure requirements for the formation of suitable molecular precursors and their N-N scission reactivity. The prospects of N2 splitting for the synthesis of nitrogen containing products will be discussed, ranging from ammonia and heterocumulenes to organic amines, amides or nitriles via proton coupled electron transfer, carbonylation, or electrophilic functionalization of N2 derived nitrido complexes. Accomplishments and challenges for nitrogen fixation via N2 splitting are presented to offer guidelines for the development of catalytic platforms.

Addictive Potential of e-Cigarettes as Reported in e-Cigarette Online Forums: Netnographic Analysis of Subjective Experiences.

BACKGROUND: While e-cigarettes usually contain nicotine, their addictive potential is not yet fully understood. We hypothesized that if e-cigarettes are addictive, users will experience typical symptoms of addiction. OBJECTIVE: The aim of our study was to investigate whether and how e-cigarette users report signs of addiction. METHODS: We identified 3 large German-language e-cigarette online forums via a systematic Google search. Based on a netnographic approach, we used deductive content analysis to investigate relevant posts in these forums. Netnography has the advantage of limiting the social desirability bias that prevails in face-to-face research, such as focus groups. The data were coded according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for tobacco use disorder, adapted for e-cigarettes. The DSM-5 criteria were used to portray a broad spectrum of possible experiences of addiction. RESULTS: Overall, 5337 threads in 3 forums were screened, and 451 threads containing relevant information were included in the analysis. Users reported experiences consistent with the DSM-5 criteria, such as craving e-cigarettes, excessive time spent vaping, and health issues related to e-cigarette use. However, our analysis also showed that users reported the absence of typical tobacco use disorder criteria, such as successful attempts to reduce the nicotine dosage. For most themes, reports of their absence were more frequent than of their presence. The absence of perceived addiction was mostly reported in contrast to prior tobacco smoking. CONCLUSIONS: This is the first study to use a netnographic approach to explore unfiltered self-reports of experiences of e-cigarette addiction by users in online forums. As hypothesized, some but not all users reported subjective experiences that corresponded to the criteria of tobacco use disorder as defined by the DSM-5. Nevertheless, subjective reports also indicated that many e-cigarette users felt in control of their behavior, especially in contrast to their prior use of tobacco cigarettes. The finding that some e-cigarette users subjectively experience addiction highlights the need for effective cessation programs to support users who experience their e-cigarette use as burdensome. This research can guide the refinement of instruments to assess e-cigarette addiction and guide cessation programs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s40359-021-00682-8.

Photoinduced Metallonitrene Formation by N2 Elimination from Azide Diradical Ligands.

Transition-metal nitrides/nitrenes are highly promising reagents for catalytic nitrogen-atom-transfer reactivity. They are typically prepared in situ upon optically induced N2 elimination from azido precursors. A full exploitation of their catalytic potential, however, requires in-depth knowledge of the primary photo-induced processes and the structural/electronic factors mediating the N2 loss with birth of the terminal metal-nitrogen core. Using femtosecond infrared spectroscopy, we elucidate here the primary molecular-level mechanisms responsible for the formation of a unique platinum(II) nitrene with a triplet ground state from a closed-shell platinum(II) azide precursor. The spectroscopic data in combination with quantum-chemical calculations provide compelling evidence that product formation requires the initial occupation of a singlet excited state with an anionic azide diradical ligand that is bound to a low-spin d8 -configured PtII ion. Subsequent intersystem crossing generates the Pt-bound triplet azide diradical, which smoothly evolves into the triplet nitrene via N2 loss in a near barrierless adiabatic dissociation. Our data highlight the importance of the productive, N2 -releasing state possessing azide ππ* character as a design principle for accessing efficient N-atom-transfer catalysts.

Stabilizing Doubly Deprotonated Diazomethane: Isolable Complexes with CN22- and CN2- Radical Ligands.

Transition metal complexes with a doubly deprotonated diazomethane (CNN2-) ligand have been proposed as fleeting intermediates in nitrogen transfer reactions. However, in contrast to isoelectronic azide (N3-), well-defined examples are unknown. We here report the synthesis and characterization of isolable complexes with terminal and bridging CNN2- ligands, stabilized by platinum(II) pincer fragments. Bonding within the allenic dimetallanitrilimine core (Pt-N═N═C-Pt) was probed by oxidation of the bridging ligand. Enhanced reactivity toward [3 + 2]-cycloaddition with CO2 was obtained. Photofragmentation favors N-NC over NN-C bond cleavage as a route to cyanide and a transient metallonitrene complex.

Blocking P2X purinoceptor 4 signalling alleviates cigarette smoke induced pulmonary inflammation.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with elevated ATP levels in the extracellular space. Once released, ATP serves as danger signal modulating immune responses by activating purinergic receptors. Accordingly, purinergic signalling has been implicated in respiratory inflammation associated with cigarette smoke exposure. However, the role of P2X4-signalling has not been fully elucidated yet. METHODS: Here, we analysed the P2X4 mRNA expression in COPD patients as well as cigarette smoke-exposed mice. Furthermore, P2X4-signalling was blocked by either using a specific antagonist or genetic depletion of P2rx4 in mice applied to an acute and prolonged model of cigarette smoke exposure. Finally, we inhibited P2X4-signalling in macrophages derived from THP-1 before stimulation with cigarette smoke extract. RESULTS: COPD patients exhibited an increased P2X4 mRNA expression in cells isolated from the bronchoalveolar lavage fluid and peripheral mononuclear cells. Similarly, P2rx4 expression was elevated in lung tissue of mice exposed to cigarette smoke. Blocking P2X4-signalling in mice alleviated cigarette smoke induced airway inflammation as well as lung parenchyma destruction. Additionally, human macrophages derived from THP-1 cells released reduced concentrations of proinflammatory cytokines in response to cigarette smoke extract stimulation when P2X4 was inhibited. CONCLUSION: Taken together, we provide evidence that P2X4-signalling promotes innate immunity in the immunopathologic responses induced by cigarette smoke exposure.

Halide Effects in Reductive Splitting of Dinitrogen with Rhenium Pincer Complexes.

Transition metal halide complexes are used as precursors for reductive N2 activation up to full splitting into nitride complexes. Distinct halide effects on the redox properties and yields are frequently observed yet not well understood. Here, an electrochemical and computational examination of reductive N2 splitting with the rhenium(III) complexes [ReX2(PNP)] (PNP = N(CH2CH2PtBu2)2 and X = Cl, Br, I) is presented. As previously reported for the chloride precursor ( J. Am. Chem. Soc.2018, 140, 7922), the heavier halides give rhenium(V) nitrides upon (electro-)chemical reduction in good yields yet with significantly anodically shifted electrolysis potentials along the halide series. Dinuclear, end-on N2-bridged complexes, [{ReX(PNP)}2(µ-N2)], were identified as key intermediates in all cases. However, while the chloride complex is exclusively formed via 2-electron reduction and ReIII/ReI comproportionation, the iodide system also reacts via an alternative ReII/ReII-dimerization mechanism at less negative potentials. This alternative pathway relies on the absence of the potential inversion after reduction and N2 activation that was observed for the chloride precursor. Computational analysis of the relevant ReIII/II and ReII/I redox couples by energy decomposition analysis attributes the halide-induced trends of the potentials to the dominating electrostatic Re-X bonding interactions over contributions from charge transfer.

Nudging and boosting children's restaurant menus for healthier food choice: a blinded quasi-randomized controlled trial in a real life setting.

BACKGROUND: Restaurants are ideal settings for implementing food interventions targeted at children. Studies with adults suggest that changes to the physical menu can lead to healthier food choices; online studies with parents indicate that specific menu designs facilitate healthier choices. However, it is unknown whether applying well-established nudging and boosting methods to children's menus also increases their choice of healthier meals in a real-world restaurant setting. METHODS: The effects of two versions of a restaurant menu on the frequency of choosing a healthy meal (newly created, healthy target dish) were tested in a blinded quasi-randomized controlled trial. The menu in the control condition contained all dishes (including the healthy target dish) in a standardized format. The intervention menu included nudging (e.g. comic character, fun attractive name for the dish) and boosting elements (e.g. information on low calorie density) next to the healthy target dish. Over five months, the control and intervention menus were switched every two weeks and records were made of how often the healthy target dish was ordered. RESULTS: In total, 607 orders were made from the children's restaurant menu (57% from the intervention menu). During the intervention phase, 4.2% of all ordered dishes from the children's menu were the healthy target dish, during the control phase, 4.4% of orders were for the target dish (p=.896). CONCLUSIONS: Contrary to our hypothesis, a modified children's menu did not lead to a significant increase in the number of orders for a healthy dish compared with a neutral control menu. Importantly, given that parents and children often choose the child's dish together, particularly boosting methods that focus on social processes and joint decision making could be promising to increase children's frequency of healthy food choices in restaurants. TRIAL REGISTRATION: DRKS00027039 , registered on 11/22/2021, (Retrospectively registered).

Associations of individual factors and early childhood education and care (ECEC) centres characteristics with preschoolers' BMI in Germany.

BACKGROUND: The number of obese children is rising worldwide. Many studies have investigated single determinants of children's body mass index (BMI), yet studies measuring determinants at different potential levels of influence are sparse. The aim of this study is to investigate the independent role of parental socioeconomic position (SEP), additional family factors at the micro level, as well as early childhood education and care (ECEC) centre characteristics at the meso level regarding BMI. METHODS: Analyses used the baseline data of the PReschool INtervention Study (PRINS) including up to 1,151 children from 53 ECEC centres. Multi-level models first estimated the associations of parental SEP indicators (parental school education, vocational training, and household income) with the children's standard deviation scores for BMI (SDS BMI, standardised for age and gender). Second, structural (number of siblings), psychosocial (strained family relationships), and nutrition behavioural (soft-drink consumption, frequency of fast-food restaurant visits) family factors at the micro level were included. Third, characteristics of the ECEC centre at the meso level in terms of average group size, the ratio of overweight children in the group, ECEC centre type (all-day care), and the location of the ECEC centre (rural vs urban) were included. All analyses were stratified by gender and adjusted for age, migration background, and parental employment status. RESULTS: Estimates for boys and girls appeared to differ. In the full model, for boys the parental SEP indicators were not related to SDS BMI. Factors related to SDS BMI in boys were: two or more siblings; B = -.55; p = 0.045 [ref.: no sibling]), the characteristics of the ECEC centre in terms of average group size (20 - 25 children; B = -.54; p = 0.022 [ref.: < 20 children]), and the ratio of overweight children (more overweight children B = -1.39; p < 0.001 [ref.: few overweight children]). For girls the number of siblings (two and more siblings; B = .67; p = 0.027 [ref.: no sibling]) and average group size (> 25 children; B = -.52; p = 0.037 [ref.: < 20 children]) were related to SDS BMI. CONCLUSIONS: The BMI of preschool children appears to be associated with determinants at the micro and meso level, however with some gender differences. The identified factors at the micro and meso level appear largely modifiable and can inform about possible interventions to reduce obesity in preschool children.

Moderating or mediating effects of family characteristics on socioeconomic inequalities in child health in high-income countries - a scoping review.

BACKGROUND: By explaining the development of health inequalities, eco-social theories highlight the importance of social environments that children are embedded in. The most important environment during early childhood is the family, as it profoundly influences children's health through various characteristics. These include family processes, family structure/size, and living conditions, and are closely linked to the socioeconomic position (SEP) of the family. Although it is known that the SEP contributes to health inequalities in early childhood, the effects of family characteristics on health inequalities remain unclear. The objective of this scoping review is to synthesise existing research on the mediating and moderating effects of family characteristics on socioeconomic health inequalities (HI) during early childhood in high-income countries. METHODS: This review followed the methodology of "Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews". To identify German and English scientific peer-reviewed literature published from January 1st, 2000, to December 19th, 2019, the following search term blocks were linked with the logical operator "AND": (1) family structure/size, processes, living conditions, (2) inequalities, disparities, diversities, (3) income, education, occupation, (4) health and (5) young children. The search covered the electronic databases PubMed, PsycINFO, and Scopus. RESULTS: The search yielded 7,089 records. After title/abstract and full-text screening, only ten peer-reviewed articles were included in the synthesis, which analysed the effects of family characteristics on HI in early childhood. Family processes (i.e., rules /descriptive norms, stress, parental screen time, parent-child conflicts) are identified to have mediating or moderating effects. While families' living conditions (i.e., TVs in children's bedrooms) are suggested as mediating factors, family structure/size (i.e., single parenthood, number of children in the household) appear to moderate health inequalities. CONCLUSION: Family characteristics contribute to health inequalities in early childhood. The results provide overall support of models of family stress and family investment. However, knowledge gaps remain regarding the role of family health literacy, regarding a wide range of children's health outcomes (e.g., oral health, inflammation parameters, weight, and height), and the development of health inequalities over the life course starting at birth.

Annual trends in Google searches provides insights related to rhinosinusitis exacerbations.

PURPOSE: Temporal trends of disease-specific internet searches may provide novel insights into seasonal dynamics of disease burden and, by extension, disease pathophysiology. The aim of this study was to define the temporal trends in rhinosinusitis-specific internet searches. METHODS: This was a cross sectional analysis of search volume for predefined search terms. Google trends was used to explore the volume of searches for five specific search terms related to rhinosinusitis: nose, mucus, sinus, sinusitis, chronic sinusitis, which were entered into Google web search between 2004 and 2019. Results were analyzed within search "context" which included temporally associated related searches. Relative search volume (RSV) was analyzed for English and non-English speaking countries from the Northern and Southern hemispheres. Analysis of seasonality was performed using the cosinor model. RESULTS: The five specific search terms were most related to rhinosinusitis-related search contexts, indicating that they were appropriately reflective of internet queries by patients for rhinosinusitis. The RSV for rhinosinusitis-related terms and more general search terms increased with each passing year indicating constant interest in rhinosinusitis. Cosinor time series analysis revealed inquiry peaks in winter months for all five specific rhinosinusitis-related search terms independent from the hemisphere. CONCLUSION: Over a 15-year period, Google searches with rhinosinusitis-specific search terms consistently peaked during the winter around the world. These findings indirectly support the model of viral infection or exposure as the predominant cause of acute rhinosinusitis and acute exacerbations of chronic rhinosinusitis.

Photoelectrochemical Conversion of Dinitrogen to Benzonitrile: Selectivity Control by Electrophile- versus Proton-Coupled Electron Transfer.

Nitride complexes are key species in homogeneous nitrogen fixation to NH3 via stepwise proton-coupled electron transfer (PCET). In contrast, direct generation of nitrogenous organic products from N2 -derived nitrides requires new strategies to enable efficient reductive nitride transfer in the presence of organic electrophiles. We here present a 2-step protocol for the conversion of dinitrogen to benzonitrile. Photoelectrochemical, reductive N2 splitting produces a rhenium(V) nitride with unfavorable PCET thermochemistry towards ammonia generation. However, N-benzoylation stabilizes subsequent reduction as a basis for selective nitrogen transfer in the presence of the organic electrophile and Brønsted acid at mild reduction potentials. This work offers a new strategy for photoelectrosynthetic nitrogen fixation beyond ammonia-to yield nitrogenous organic products.

Rhenium-Mediated Conversion of Dinitrogen and Nitric Oxide to Nitrous Oxide.

Reductive splitting of N2 is an attractive strategy towards nitrogen fixation beyond ammonia at ambient conditions. However, the resulting nitride complexes often suffer from thermodynamic overstabilization hampering functionalization. Furthermore, oxidative nitrogen atom transfer of N2 derived nitrides remains unknown. We here report a ReIV pincer platform that mediates N2 splitting upon chemical reduction or electrolysis with unprecedented yield. The N2 derived ReV nitrides undergo facile nitrogen atom transfer to nitric oxide, giving nitrous oxide nearly quantitatively. Experimental and computational results indicate that outer-sphere ReN/NO radical coupling is facilitated by the activation of the nitride via initial coordination of NO.