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Evolutionary selection in nature has led to hierarchical structuring as a fundamental optimization strategy for biological structures, maximizing functional performance while minimizing resource usage. Precise hierarchical organization of natural materials over a wide range of length scales gives rise to unique synergistic properties that could not be achieved by single components. Despite the clear advantages offered by hierarchically structuring matter, mastering hierarchical control based on the current synthetic toolbox is still a challenge. In this review, some recent advancements in the fabrication of hierarchical metal organic framework (MOF) materials are highlighted and the advantages that arise due to different kinds of MOF hierarchy are critically analyzed. The special focus of the review lies in highlighting the applications where MOF hierarchical materials can be most impactful and describing characterization techniques currently at the disposal of scientists for the precise characterization of MOF hierarchical structures across all length scales. Finally, the intent is to inspire reticular chemists to master hierarchical control of MOF materials so as to fully utilize the advantages MOFs offer for various applications. [ABSTRACT FROM AUTHOR]

Aim: To identify new biomarkers to detect untreated and treated periodontitis in gingival crevicular fluid (GCF) using sequential window acquisition of all theoretical mass spectra (SWATH‐MS). Materials and Methods: GCF samples were collected from 44 periodontally healthy subjects and 40 with periodontitis (Stages III–IV). In the latter, 25 improved clinically 2 months after treatment. Samples were analysed using SWATH‐MS, and proteins were identified by the UniProt human‐specific database. The diagnostic capability of the proteins was determined with generalized additive models to distinguish the three clinical conditions. Results: In the untreated periodontitis vs. periodontal health modelling, five proteins showed excellent or good bias‐corrected (bc)‐sensitivity/bc‐specificity values of >80%. These were GAPDH, ZG16B, carbonic anhydrase 1, plasma protease inhibitor C1 and haemoglobin subunit beta. GAPDH with MMP‐9, MMP‐8, zinc‐α‐2‐glycoprotein and neutrophil gelatinase‐associated lipocalin and ZG16B with cornulin provided increased bc‐sensitivity/bc‐specificity of >95%. For distinguishing treated periodontitis vs. periodontal health, most of these proteins and their combinations revealed a predictive ability similar to previous modelling. No model obtained relevant results to differentiate between periodontitis conditions. Conclusions: New single and dual GCF protein biomarkers showed outstanding results in discriminating untreated and treated periodontitis from periodontal health. Periodontitis conditions were indistinguishable. Future research must validate these findings. [ABSTRACT FROM AUTHOR]

This paper analyses the impact of a healthy food nudge intervention on purchases of 1590 customers of a supermarket chain's loyalty program in Uruguay through a randomized controlled trial. Nudges were presented in the form of messages sent through WhatsApp to customers three times a week for 8 weeks (between July and September 2020). Messages highlighted the benefits of cooking at home and eating mindfully and healthy (vegetables, fruits, healthy snacks, legumes, and fish), and included easy to implement tips. Results show that, on average, customers assigned to the treatment group increased their purchases of healthy food by 8% and substituted sugar‐sweetened for sugar‐free beverages. We find an unintended increase in purchases of unhealthy food of 7%, with no correlative increase in calories, suggesting that customers substituted higher calorie products for lower calorie ones. We find that households with lower educational attainment, lower income, and with children under the age of 12 are more likely to increase purchases of fruits and vegetables, while other households are more likely to improve the diet quality without increasing expenditure. Effects do not persist after the intervention is over, suggesting that salience, rather than information is the main channel triggering the effects. [ABSTRACT FROM AUTHOR]

The criteria for clinical diagnosis of neurofibromatosis type 1 (NF1) are not sensitive in young children. Recognition is easier when one of their parents has been diagnosed with this condition, and the causal mutation is known. We present a case of a girl with isolated café‐au‐lait spots, whose father was diagnosed with NF1. However, both were found to carry different de novo mutations in the NF1 gene. This possibility has significant implications for the diagnostic process and genetic counseling. [ABSTRACT FROM AUTHOR]

Autistic individuals can experience difficulties with attention reorienting and Theory of Mind (ToM), which are closely associated with anterior and posterior subdivisions of the right temporoparietal junction. While the link between these processes remains unclear, it is likely subserved by a dynamic crosstalk between these two subdivisions. We, therefore, examined the dynamic functional connectivity (dFC) between the anterior and posterior temporoparietal junction, as a biological marker of attention and ToM, to test its contribution to the manifestation of autistic trait expression in Autism Spectrum Condition (ASC). Two studies were conducted, exploratory (14 ASC, 15 TD) and replication (29 ASC, 29 TD), using resting‐state fMRI data and the Social Responsiveness Scale (SRS) from the Autism Brain Imaging Data Exchange repository. Dynamic Independent Component Analysis was performed in both datasets using the CONN toolbox. An additional sliding‐window analysis was performed in the replication study to explore different connectivity states (from highly negatively to highly positively correlated). Dynamic FC was reduced in ASC compared to TD adults in both the exploratory and replication datasets and was associated with increased SRS scores (especially in ASC). Regression analyses revealed that decreased SRS autistic expression was predicted by engagement of highly negatively correlated states, while engagement of highly positively correlated states predicted increased expression. These findings provided consistent evidence that the difficulties observed in ASC are associated with altered patterns of dFC between brain regions subserving attention reorienting and ToM processes and may serve as a biomarker of autistic trait expression. Lay Summary: Autistic individuals may have difficulties with redirecting their attention and understanding others' thoughts and it is possible that there is a direct link between the interaction of these two functions and the level of social difficulties in autism. One way to test this link is by assessing how different brain regions associated with these functions are communicating with each other and working in synchrony. The present study focused on two subdivisions of a brain region called the temporoparietal junction, which has been associated with attention and understanding others' thoughts. Our aim was to assess the dynamic communication between these subdivisions in autistic and non‐autistic individuals and whether differences in this dynamic communication might be related to higher or lower expressions of social difficulties. Using brain scans from two different groups of 29 and 58 participants, we found that communication between these brain regions was less dynamic in autistic individuals in both groups. Moreover, reduced dynamic communication between these two subdivisions of the temporoparietal junction was associated with greater social difficulties. Across the two groups, we show consistent results whereby some of the social difficulties observed in autistic individuals might arise from reduced dynamic communication between brain areas linked to attention and understanding of others' thoughts. This insight adds to our understanding of how the spectrum of autistic traits might be rooted in the brain's communication patterns and advances the search for biological markers of autism. [ABSTRACT FROM AUTHOR]

Introduction: Plasma exchange (PE) is widely used in many immune‐based neurological diseases. Our aim is to analyze characteristics of PE in neurological patients at the Clinical Center of Montenegro. Methods: Our study involved neurological patients treated with PE between January 2020 and April 2022. Results: In total, 246 PEs were performed in 43 patients. We divided patients into 4 groups according to indications. In 8/9 multiple sclerosis (MS) patients a decrease of Expanded Dysability Status Scale at least 0.5 was verified. In 14/20 Guillain Barre syndrome patients reduction of Hughes was observed. Four patients with myasthenia gravis (MG) were treated with PE. The most heterogeneous group (4) consisted of patients in whom the mechanism of disease development is assumed to be immune system dysregulation. Fourteen patients had any adverse event. Conclusion: Our results show that PE is widely used and safe in the treatment of neurological diseases. [ABSTRACT FROM AUTHOR]

Aim: To determine the accuracy of biomarker combinations in gingival crevicular fluid (GCF) and saliva through meta‐analysis to diagnose periodontitis in systemically healthy subjects. Methods: Studies on combining two or more biomarkers providing a binary classification table, sensitivity/specificity values or group sizes in subjects diagnosed with periodontitis were included. The search was performed in August 2022 through PUBMED, EMBASE, Cochrane, LILACS, SCOPUS and Web of Science. The methodological quality of the articles selected was evaluated using the QUADAS‐2 checklist. Hierarchical summary receiver operating characteristic modelling was employed to perform the meta‐analyses (CRD42020175021). Results: Twenty‐one combinations in GCF and 47 in saliva were evaluated. Meta‐analyses were possible for six salivary combinations (median sensitivity/specificity values): IL‐6 with MMP‐8 (86.2%/80.5%); IL‐1β with IL‐6 (83.0%/83.7%); IL‐1β with MMP‐8 (82.7%/80.8%); MIP‐1α with MMP‐8 (71.0%/75.6%); IL‐1β, IL‐6 and MMP‐8 (81.8%/84.3%); and IL‐1β, IL‐6, MIP‐1α and MMP‐8 (76.6%/79.7%). Conclusions: Two‐biomarker combinations in oral fluids show high diagnostic accuracy for periodontitis, which is not substantially improved by incorporating more biomarkers. In saliva, the dual combinations of IL‐1β, IL‐6 and MMP‐8 have an excellent ability to detect periodontitis and a good capacity to detect non‐periodontitis. Because of the limited number of biomarker combinations evaluated, further research is required to corroborate these observations. [ABSTRACT FROM AUTHOR]

The multi‐batch reanalysis approach of jointly reevaluating gene/genome sequences from different works has gained particular relevance in the literature in recent years. The large amount of 16S ribosomal ribonucleic acid (rRNA) gene sequence data stored in public repositories and information in taxonomic databases of the same gene far exceeds that related to complete genomes. This review is intended to guide researchers new to studying microbiota, particularly the oral microbiota, using 16S rRNA gene sequencing and those who want to expand and update their knowledge to optimise their decision‐making and improve their research results. First, we describe the advantages and disadvantages of using the 16S rRNA gene as a phylogenetic marker and the latest findings on the impact of primer pair selection on diversity and taxonomic assignment outcomes in oral microbiome studies. Strategies for primer selection based on these results are introduced. Second, we identified the key factors to consider in selecting the sequencing technology and platform. The process and particularities of the main steps for processing 16S rRNA gene‐derived data are described in detail to enable researchers to choose the most appropriate bioinformatics pipeline and analysis methods based on the available evidence. We then produce an overview of the different types of advanced analyses, both the most widely used in the literature and the most recent approaches. Several indices, metrics and software for studying microbial communities are included, highlighting their advantages and disadvantages. Considering the principles of clinical metagenomics, we conclude that future research should focus on rigorous analytical approaches, such as developing predictive models to identify microbiome‐based biomarkers to classify health and disease states. Finally, we address the batch effect concept and the microbiome‐specific methods for accounting for or correcting them. [ABSTRACT FROM AUTHOR]

Biologicals have transformed the management of severe disease phenotypes in psoriasis and are often prescribed in women of childbearing age. However, information on safety of biologicals in pregnancy are lacking. We conducted a systematic review and meta‐analysis aimed to describe the characteristics and pregnancy outcomes in women with psoriasis exposed to biologics within 3 months before or during pregnancy, and to estimate the pooled prevalence of spontaneous, elective and total abortions, and congenital malformations in their newborns. Bibliographic searches were performed in the PubMed, Embase, Scopus and Web of Science databases up to 14 April 2022. No restrictions on sample size or publication date were applied. Review performance complied with PRISMA guidelines, and two reviewers assessed randomized controlled trials and nonrandomized studies reporting pregnancy outcomes in women exposed to biologics indicated for psoriasis during the pre‐gestational and/or gestational period. Studies focusing on rheumatologic or gastroenterological immune‐mediated inflammatory diseases were excluded. Regardless of data heterogeneity, a random‐effects model was used to pool prevalence estimates. We included 51 observational studies, involving 739 pregnancies exposed to approved biologics for psoriasis. Administration was mostly (70.4%) limited to the first trimester, and the most common drug was ustekinumab (36.0%). The estimated prevalence of miscarriage was 15.3% (95% confidence interval [CI] 12.7–18.0) and elective abortions, 10.8% (95% CI 7.7–14.3). Congenital malformations occurred in about 3.0% (95% CI 1.6–4.8) of live births exposed to biologics during pregnancy. Altogether, exposure to biologics for psoriasis during pregnancy and/or conception does not seem to be associated with an increased risk of miscarriage/abortion or congenital malformations, showing similar rates to the general population. These results suggest that biologic drugs are safe and pose an acceptable risk to the foetuses/neonates. [ABSTRACT FROM AUTHOR]

Double aortic arch (DAA) is a rare, congenital anomaly in small animals, resulting in a complete vascular ring encircling the esophagus and trachea, and subsequent compression of these organs. Few studies have reported utilizing CT angiography (CTA) for diagnosing DAA in dogs; thus, the imaging features are currently lacking in the literature. The objectives of this retrospective, multicenter, descriptive case series were to report the clinical and CTA characteristics of DAA in surgically treated cases. Medical records and CTA images were reviewed. Six juvenile dogs met the inclusion criteria (median age: 4.2 months; range: 2–5 months). The most common clinical signs included chronic regurgitation (100%), decreased body condition (67%), and coughing (50%). Common CTA features of DAA included a dominant left aortic arch (median diameter: 8.1 mm) and minor right aortic arch (median diameter: 4.3 mm; 83%), an aberrant right subclavian artery arising directly from the right aortic arch (83%), segmental esophageal constriction (100%), and variable degrees of dilation cranial to the heart base, and marked tracheal luminal compression (median percent change: –55%; 100%) and leftward curvature of the trachea at the level of the bifurcation of the aortic arches (100%). All dogs underwent successful surgical correction with only minor postoperative complications. Due to the similarity of clinical and imaging characteristics described to that of other forms of vascular ring anomalies (VRA), CTA is vital for the specific diagnosis of DAA in dogs. [ABSTRACT FROM AUTHOR]

Fermentation employing Saccharomyces cerevisiae has produced alcoholic beverages and bread for millennia. More recently, S. cerevisiae has been used to manufacture specific metabolites for the food, pharmaceutical, and cosmetic industries. Among the most important of these metabolites are compounds associated with desirable aromas and flavors, including higher alcohols and esters. Although the physiology of yeast has been well‐studied, its metabolic modulation leading to aroma production in relevant industrial scenarios such as winemaking is still unclear. Here we ask what are the underlying metabolic mechanisms that explain the conserved and varying behavior of different yeasts regarding aroma formation under enological conditions? We employed dynamic flux balance analysis (dFBA) to answer this key question using the latest genome‐scale metabolic model (GEM) of S. cerevisiae. The model revealed several conserved mechanisms among wine yeasts, for example, acetate ester formation is dependent on intracellular metabolic acetyl‐CoA/CoA levels, and the formation of ethyl esters facilitates the removal of toxic fatty acids from cells using CoA. Species‐specific mechanisms were also found, such as a preference for the shikimate pathway leading to more 2‐phenylethanol production in the Opale strain as well as strain behavior varying notably during the carbohydrate accumulation phase and carbohydrate accumulation inducing redox restrictions during a later cell growth phase for strain Uvaferm. In conclusion, our new metabolic model of yeast under enological conditions revealed key metabolic mechanisms in wine yeasts, which will aid future research strategies to optimize their behavior in industrial settings. [ABSTRACT FROM AUTHOR]

Saccharomyces non‐cerevisiae yeasts are gaining momentum in wine fermentation due to their potential to reduce ethanol content and achieve attractive aroma profiles. However, the design of the fermentation process for new species requires intensive experimentation. The use of mechanistic models could automate process design, yet to date, most fermentation models have focused on primary metabolism. Therefore, these models do not provide insight into the production of secondary metabolites essential for wine quality, such as aromas. In this work, we formulate a continuous model that accounts for the physiological status of yeast, that is, exponential growth, growth under nitrogen starvation and transition to stationary or decay phases. To do so, we assumed that nitrogen starvation is associated with carbohydrate accumulation and the induction of a set of transcriptional changes associated with the stationary phase. The model accurately described the dynamics of time series data for biomass and primary and secondary metabolites obtained for various yeast species in single culture fermentations. We also used the proposed model to explore different process designs, showing how the addition of nitrogen could affect the aromatic profile of wine. This study underlines the potential of incorporating yeast physiology into batch fermentation modelling and provides a new means of automating process design. [ABSTRACT FROM AUTHOR]

This article discusses the unequal impact of Covid‐19 on the lives of the children of survivors of modern slavery, child victims of exploitation and children at risk of exploitation in the UK. It draws on research that has analysed the risks and impacts of Covid‐19 on victims and survivors of modern slavery. It explores how pandemic responses may have hindered these children's rights to education, food, safety, development and participation and representation in legal processes. It suggests that the pandemic should be used as an impetus to address inequalities that existed pre‐Covid‐19 and those that have been exacerbated by it. [ABSTRACT FROM AUTHOR]

The precursor conversion chemistry and surface chemistry of Cu3N and Cu3PdN nanocrystals are unknown or contested. Here, we first obtain phase‐pure, colloidally stable nanocubes. Second, we elucidate the pathway by which copper(II) nitrate and oleylamine form Cu3N. We find that oleylamine is both a reductant and a nitrogen source. Oleylamine is oxidized by nitrate to a primary aldimine, which reacts further with excess oleylamine to a secondary aldimine, eliminating ammonia. Ammonia reacts with CuI to form Cu3N. Third, we investigated the surface chemistry and find a mixed ligand shell of aliphatic amines and carboxylates (formed in situ). While the carboxylates appear tightly bound, the amines are easily desorbed from the surface. Finally, we show that doping with palladium decreases the band gap and the material becomes semi‐metallic. These results bring insight into the chemistry of metal nitrides and might help the development of other metal nitride nanocrystals. [ABSTRACT FROM AUTHOR]

Background: Limited information currently exists regarding the clinical progression and outcomes of cats that undergo choledochal stenting as a treatment for extrahepatic biliary obstruction (EHBO). Hypothesis/Objectives: Describe clinical characteristics, indications for choledochal stent placement, procedure, and outcomes in a cohort of cats undergoing choledochal stenting and evaluate risk factors associated with survival as well as recurrence of EHBO in affected cats. Animals Twenty‐three client‐owned cats undergoing choledochal stent placement. Methods: Retrospective study. Medical records from 6 academic institutions were reviewed, and data were extracted and analyzed statistically. Results: Median age of cats was 10.1 years (range, 2‐16), and all cats had at least 2 clinical signs. Most common clinical signs were vomiting in 20/22 (90.9%), inappetence in 19/22 (86.4%), and lethargy in 19/23 (82.6%). Procedural complications were uncommon and rarely related to the stenting procedure. Clinical signs improved postoperatively in 15/20 (75.0%) cats and serum total bilirubin concentration decreased postoperatively in 13/19 (68.4%) cats. Eighteen (78.3%) cats survived to discharge. Recurrence of EHBO was documented in 7/18 (38.9%) cats that survived to discharge. Cholelithiasis was associated with recurrence of EHBO. Median survival time for cats that survived to discharge was 931 days (range, 19‐3034). Absence of peritoneal effusion was associated with survival to discharge. Conclusions and Clinical Importance: Choledochal stenting was an effective treatment modality in cats with EHBO with few procedural complications and potential for prolonged survival, but substantial risk for recurrence of EHBO was identified. [ABSTRACT FROM AUTHOR]

Copper complexes are promising candidates for anticancer drugs, because of their redox properties and the ability to generate ROS (reactive oxygen species) in the cellular media. Most of the reported complexes with anticancer properties are based on Cu(II), which must be reduced to Cu(I) to exert the therapeutic action. Here, we report on the synthesis and characterization of two novel copper(I) complexes, a mononuclear complex [Cu(L1)2](ClO4) (1) and a binuclear helicate [Cu2(L2)2](ClO4)2(2) (L1=2‐ethoxy‐1,10‐phenanthroline, L2=1,2‐bis((1,10‐phenanthrolin‐2‐yl)oxy)ethane), which were designed to be structurally comparable, in order to evaluate the effect of nuclearity on the artificial nuclease activity. The activity of helicate (2) was higher than that of the monometallic (1), and the DNA cleavage mechanism is through the generation of hydroxyl radical in a Fenton‐like reaction, which occurs after oxidation of Cu(I) by O2. Also, helicate (2) showed a higher cytotoxic effect against different cancer cells lines, while both complexes are more active than cisplatin. [ABSTRACT FROM AUTHOR]

Objective: Previously, only the HLA–DRB1 alleles have been assessed in rheumatoid arthritis (RA). The aim of the present study was to identify the key major histocompatibility complex (MHC) susceptibility factors showing a significant association with anti–carbamylated protein antibody–positive (anti‐CarP+) RA. Methods: Analyses were restricted to RA patients who were anti–cyclic citrullinated peptide antibody negative (anti‐CCP−), because the anti‐CCP status dominated the results otherwise. Therefore, we studied samples from 1,821 anti‐CCP− RA patients and 6,821 population controls from Spain, Sweden, and the Netherlands. The genotypes for ~8,000 MHC biallelic variants were assessed by dense genotyping and imputation. Their association with the anti‐CarP status in RA patients was tested with logistic regression and combined with inverse‐variance meta‐analysis. Significance of the associations was assessed according to a study‐specific threshold of P < 2.0 × 10−5. Results: The HLA–B*08 allele and its correlated amino acid variant Asp‐9 showed a significant association with anti‐CarP+/anti‐CCP− RA (P < 3.78 × 10−7; I2 = 0). This association was specific when assessed relative to 3 comparator groups: population controls, anti‐CarP−/anti‐CCP− RA patients, and anti‐CCP− RA patients who were positive for other anti–citrullinated protein antibodies. Based on these findings, anti‐CarP+/anti‐CCP− RA patients could be separated from other antibody‐defined subsets of RA patients in whom an association with the HLA–B*08 allele has been previously demonstrated. No other MHC variant remained associated with anti‐CarP+/anti‐CCP− RA after accounting for the presence of the HLA–B*08 allele. Specifically, the reported association of HLA–DRB1*03 was observed at a level comparable to that reported previously, but it was attributable to linkage disequilibrium. Conclusion: These results identify HLA–B*08 carrying Asp‐9 as the MHC locus showing the strongest association with anti‐CarP+/anti‐CCP− RA. This knowledge may help clarify the role of the HLA in susceptibility to specific subsets of RA, by shaping the spectrum of RA autoantibodies. [ABSTRACT FROM AUTHOR]

Thiosemicarbazone moiety is a valuable scaffold for the synthesis of metallic complexes with anticancer purposes, when bearing N‐heterocyclic the final compounds possess diverse biological activities. Using thiazole as bioisosteres, the resulting thiosemicarbazones can afford synthetic drugs with a variety of pharmacological effects. Trying to elucidate, if metal complexes from α‐N‐heterocyclic thiosemicarbazones can achieve more selectivity versus special tumor lines, we have developed new metal complexes with 1H imidazole‐4‐carboxaldehyde 4 N‐p‐tolyl‐ and 4 N‐phenylthiosemicarbazone (HL1 and HL2 respectively). The solution studies of these ligands showed a tautomeric equilibria in solution and their reaction with Li2PdCl4 proved the stability of both forms affording two mononuclear Pd(II) complexes. Both tautomeric forms are clearly coordinated to palladium center acting as two different bidentate ligands. Palladium complexes' stability in biological buffers was investigated to stablish the optimal conditions for the evaluation of cytotoxicity, that on the triple negative adenocarcinoma cell line showed IC50 values in the low micromolar range. Complexes were also studied with CT DNA (UV‐Visible spectroscopy and viscosity) and with the pBR322 plasmid supercoiled models, indicating non covalent interaction. [ABSTRACT FROM AUTHOR]

With the implementation of the National Integrated Health System in 2007, the Uruguayan government extended social health insurance (SHI) to groups of individuals previously covered by the public safety net (PSN) or that paid for private insurance out‐of‐pocket. The policy allowed new beneficiaries to choose care from a set of private providers. In this study, we focus on the extension of SHI to adolescent mothers previously covered by the PSN. Exploiting the gradual incorporation of children of formal workers during the 2008–2013 period, and the geographic variation in the intensity of the reform, we find suggestive evidence that the increase in choice associated to the expansion of SHI decreased adolescent fertility, improved prenatal care and birthweight, and decreased first year mortality among low birthweight infants. These effects were only observed in the medium run, suggesting initial choice frictions and input shortage. We provide evidence that families increased their choice of private providers and that market concentration decreased in certain areas of the country, supporting the hypothesis that choice, and possibly competition, were the main mechanisms behind the findings. [ABSTRACT FROM AUTHOR]

Background: In recent decades, many self‐report instruments have been developed to assess the extent to which patients want to be informed and involved in decisions about their health as part of the concept of person‐centred care (PCC). The main objective of this research was to translate, adapt and validate the Patient‐Practitioner Orientation Scale (PPOS) using a sample of primary care health‐care professionals in Spain. Methods: Baseline analysis of PPOS scores for 321 primary care professionals (general practitioners and nurses) from 63 centres and 3 Spanish regions participating in a randomized controlled trial. We analysed missing values, distributions and descriptive statistics, item‐to‐scale correlations and internal consistency. Performed were confirmatory factor analysis (CFA) of the 2‐factor model (sharing and caring dimensions), scale depuration and principal component analysis (PCA). Results: Low inter‐item correlations were observed, and the CFA 2‐factor model only obtained a good fit to the data after excluding 8 items. Internal consistency of the 10‐item PPOS was acceptable (0.77), but low for individual subscales (0.70 and 0.55). PCA results suggest a possible 3‐factor structure. Participants showed a patient‐oriented style (mean = 4.46, SD = 0.73), with higher scores for caring than sharing. Conclusion: Although the 2‐factor model obtained empirical support, measurement indicators of the PPOS (caring dimension) could be improved. Spanish primary care health‐care professionals overall show a patient‐oriented attitude, although less marked in issues such as patients' need for and management of medical information. [ABSTRACT FROM AUTHOR]

In their attempts to associate the nationalistic ideology with speculative promises to emancipate the people from malevolent 'outsiders', right‐wing populists often engage with rural and agricultural topics. Meanwhile, green parties, commonly associated with the progressive ideas of environmentally friendly agriculture, occasionally employ the binary logic of agrarian populism. This paper has three objectives. First, to identify the discursive features of rural (right‐wing and agrarian) populism. Second, to examine how these discursive differences unfold in agricultural, party politics. Third, to examine the implications of overlapping ideas of populist and green parties for emancipatory rural politics. The study is predominantly based on the analysis of political discourses in Hungary: Jobbik (right‐wing populist) and LMP (green party), while the agricultural discourse of Fidesz, the ruling right‐wing populist party will serve as the background to the analysis. Particular attention is given to the aesthetic, symbolic, and material dimensions of land in discourse, including environmentally friendly farming and the EU's Common Agricultural Policy (CAP). [ABSTRACT FROM AUTHOR]

Aim: To obtain salivary interleukin (IL) 1β‐based models to predict the probability of the occurrence of periodontitis, differentiating by smoking habit. Materials/Methods: A total of 141 participants were recruited, 62 periodontally healthy controls and 79 subjects affected by periodontitis. Fifty of the diseased patients were given non‐surgical periodontal treatment and showed significant clinical improvement in 2 months. IL1β was measured in the salivary samples using the Luminex instrument. Binary logistic regression models were obtained to differentiate untreated periodontitis from periodontal health (first modelling) and untreated periodontitis from treated periodontitis (second modelling), distinguishing between non‐smokers and smokers. The area under the curve (AUC) and classification measures were calculated. Results: In the first modelling, IL1β presented AUC values of 0.830 for non‐smokers and 0.689 for smokers (accuracy = 77.6% and 70.7%, respectively). In the second, the predictive models revealed AUC values of 0.671 for non‐smokers and 0.708 for smokers (accuracy = 70.0% and 75.0%, respectively). Conclusion: Salivary IL1β has an excellent diagnostic capability when it comes to distinguishing systemically healthy patients with untreated periodontitis from those who are periodontally healthy, although this discriminatory potential is reduced in smokers. The diagnostic capacity of salivary IL1β remains acceptable for differentiating between untreated and treated periodontitis. [ABSTRACT FROM AUTHOR]

RNA‐based therapies offer a wide range of therapeutic interventions including the treatment of skin diseases; however, the strategies to efficiently deliver these biomolecules are still limited due to obstacles related to the cellular uptake and cytoplasmic delivery. Herein, we report the synthesis of a triggerable polymeric nanoparticle (NP) library composed of 160 formulations, presenting physico‐chemical diversity and differential responsiveness to light. Six formulations were more efficient (up to 500 %) than commercially available lipofectamine in gene‐knockdown activity. These formulations showed differential internalization by skin cells and the endosomal escape was rapid (minutes range). The NPs were effective in the release of siRNA and miRNA. Acute skin wounds treated with the top hit NP complexed with miRNA‐150‐5p healed faster than wounds treated with scrambled miRNA. Light‐activatable NPs offer a new strategy to topically deliver non‐coding RNAs. [ABSTRACT FROM AUTHOR]

Aim: To analyse, using a meta‐analytical approach, the diagnostic accuracy of single molecular biomarkers in saliva for the detection of periodontitis in systemically healthy subjects. Materials and Methods: Articles on molecular biomarkers in saliva providing a binary contingency table (or sensitivity and specificity values and group sample sizes) in individuals with clinically diagnosed periodontitis were considered eligible. Searches for candidate articles were conducted in six electronic databases. The methodological quality was assessed through the tool Quality Assessment of Diagnostic Studies. Meta‐analyses were performed using the Hierarchical Summary Receiver Operating Characteristic model. Results: Meta‐analysis was possible for 5 of the 32 biomarkers studied. The highest values of sensitivity for the diagnosis of periodontitis were obtained for IL1beta (78.7%), followed by MMP8 (72.5%), IL6 and haemoglobin (72.0% for both molecules); the lowest sensitivity value was for MMP9 (70.3%). In terms of specificity estimates, MMP9 had the best result (81.5%), followed by IL1beta (78.0%) and haemoglobin (75.2%); MMP8 had the lowest specificity (70.5%). Conclusions: MMP8, MMP9, IL1beta, IL6 and Hb were salivary biomarkers with good capability to detect periodontitis in systemically healthy subjects. MMP8 and IL1beta are the most researched biomarkers in the field, both showing clinically fair effectiveness for the diagnosis of periodontitis. [ABSTRACT FROM AUTHOR]

Background: Lower urinary tract transitional cell carcinoma (TCC) is an important but rarely described disease of cats. Objectives: To report the clinical characteristics, treatments, and outcomes in a cohort of cats with lower urinary tract TCC and to test identified variables for prognostic relevance. Animals: One‐hundred eighteen client‐owned cats with lower urinary tract carcinoma. Methods: Medical records were retrospectively reviewed to obtain information regarding clinical characteristics, treatments, and outcomes. Recorded variables were analyzed statistically. Results: Median age of affected cats was 15 years (range, 5.0‐20.8 years) and median duration of clinical signs was 30 days (range, 0‐730 days). The trigone was the most common tumor location (32/118; 27.1%) as assessed by ultrasound examination, cystoscopy, or both. Treatment was carried out in 73 of 118 (61.9%) cats. Metastatic disease was documented in 25 of 118 (21.2%) cats. Median progression‐free survival and survival time for all cats were 113 days (95% confidence interval [CI], 69‐153) and 155 days (95% CI, 110‐222), respectively. Survival increased significantly (P <.001) when comparing cats across the ordered treatment groups: no treatment, treatment without partial cystectomy, and treatment with partial cystectomy. Partial cystectomy (hazard ratio [HR], 0.31; 95% CI, 0.17‐0.87) and treatment with nonsteroidal anti‐inflammatory drugs (HR, 0.55; 95% CI, 0.33‐0.93) were significantly associated with longer survival times. Conclusions and Clinical Importance: The results support treatment using partial cystectomy and NSAIDs in cats with TCC. [ABSTRACT FROM AUTHOR]

Aim: To analyse, by means of a meta‐analytical approach, the diagnostic accuracy of molecular biomarkers in gingival crevicular fluid (GCF) for the detection of periodontitis in systemically healthy subjects. Material and Methods: Studies on GCF molecular biomarkers providing a binary classification table (or sensitivity and specificity values and group sample sizes) in individuals with clinically diagnosed periodontitis were considered eligible. The search was performed using six electronic databases. The methodological quality of studies was assessed through the tool Quality Assessment of Diagnostic Studies. Meta‐analyses were performed using the Hierarchical Summary Receiver Operating Characteristic, which adjusts classification data using random effects logistic regression. Results: The included papers identified 36 potential biomarkers for the detection of periodontitis and for four of them meta‐analyses were performed. The median sensitivity and specificity were for MMP8, 76.7% and 92.0%; for elastase, 74.6% and 81.1%; for cathepsin, 72.8% and 67.3%, respectively. The worst estimates of sensitivity and specificity were for trypsin (71.3% and 66.1%, respectively). Conclusions: MMP8 showed good sensitivity and excellent specificity, which resulted in this biomarker being clinically the most useful or effective for the diagnosis of periodontitis in systemically healthy subjects, regardless of smoking condition. [ABSTRACT FROM AUTHOR]

Rectal prolapse can cause mucous discharge or rectal bleeding [[1]], haemorrhage, faecal incontinence (in 50%-75%) or constipation as the main symptoms. Rectal prolapse, described as a full-thickness intussusception of the rectal wall protruding externally through the anus [[1]], is a rare condition that occurs in 0.5% of the general population but is more common in elderly women, with a peak age of 70 years [[1]]. Therefore, we conclude that Delorme procedure is a valid, safe and effective [[3]] technique for a specific group of patients as a treatment for rectal prolapse, with an acceptable recurrence rate (10%-15%) [[1], [4]] and the option of a second approach, abdominally, in cases of early recurrence [[4]]. [Extracted from the article]

Likely due to specific regulatory requirements in the United States, physicians sometimes interpret interchangeability as the potential for a biologic to be substituted by a biosimilar at the pharmacy level, without the involvement of a physician. However, interchangeability between a biological reference medicine and a corresponding biosimilar medicine should not be defined by its practical application; whether physician-driven switch or pharmacist-driven substitution. Despite the strength of the science supporting interchangeability, when two medicines are deemed to be interchangeable, physicians should be relevant players in any switching decision. A science-based understanding of interchangeability may raise confidence among physicians that currently prescribe biosimilars only in naïve patients, and may make them more comfortable switching from the reference medicine to a biosimilar, to further foster the positive impact of biosimilars. [Extracted from the article]

Objective: To evaluate the efficacy and safety of increasing the dose interval of subcutaneous tocilizumab (TCZ‐SC) in patients with rheumatoid arthritis (RA) who are in clinical remission. Methods: RA patients with active disease and an inadequate response to conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) or to a biologic agent were entered into a single‐arm treatment phase with 162 mg of TCZ‐SC administered once weekly (TCZ‐SC 162 mg qw) as monotherapy or in combination with a csDMARD for 24 weeks. Patients who achieved clinical remission at weeks 20 and 24 were randomized to continue with the same regimen or to switch to 162 mg TCZ‐SC administered every 2 weeks (TCZ‐SC 162 mg q2w) for 24 weeks (open‐label). Patients with a Disease Activity Score in 28 joints (DAS28) of <2.6 were considered to be in clinical remission. Results: In total, 179 (45%) of 401 patients in the single‐arm phase achieved clinical remission and were randomized to continue to receive TCZ‐SC 162 mg qw (n = 89) or to switch to TCZ‐SC 162 mg q2w (n = 90) for 24 weeks. At week 48, significantly more patients treated with TCZ‐SC 162 mg qw remained in clinical remission compared to patients who received TCZ‐SC 162 mg q2w (90% versus 73%; P = 0.004). The results of other efficacy measures revealed greater efficacy with TCZ‐SC 162 mg qw, but none of the efficacy outcomes in this group were significantly different from those in patients treated with TCZ‐SC 162 mg q2w, except for the mean change from baseline in the DAS28 score at week 48 (mean change −4.07 points [SD 1.29] versus −3.65 points [SD 1.35]; P = 0.034). Tolerability and safety parameters were similar between the treatment groups. Conclusion: Increasing the dose interval of TCZ‐SC in patients with RA was associated with a lower likelihood of maintaining remission after 24 weeks and was not associated with better tolerability. However, most patients were able to sustain remission with a half‐dose of TCZ‐SC, and therefore this strategy deserves further investigation. [ABSTRACT FROM AUTHOR]

Objective: Recognition of a new type of rheumatoid arthritis (RA)–specific autoantibody, the anti–carbamylated protein antibodies (anti‐CarP), has provided an opportunity to improve the management and understanding of RA. The current study was undertaken to assess the relationship between anti‐CarP antibodies and HLA–DRB1 alleles in RA. Methods: Serum samples were obtained from 3 different collections, comprising a total of 1,126 RA patients. Serum reactivity against in vitro carbamylated fetal calf serum proteins was determined by enzyme‐linked immunosorbent assay. HLA–DRB1 alleles were determined using either hybridization techniques or imputation from HLA‐dense genotypes. Results of these analyses were combined in a meta‐analysis with data from 3 previously reported cohorts. The carrier frequencies of the common HLA–DRB1 alleles were compared between the antibody‐positive RA subgroups and the double‐negative subgroup of RA patients stratified by anti–citrullinated protein antibody (ACPA)/anti‐CarP antibody status, and also between the 4 RA patient strata and healthy controls. Results: Meta‐analysis was conducted with 3,709 RA patients and 2,305 healthy control subjects. Results revealed a significant increase in frequency of HLA–DRB1*03 carriers in the ACPA−/anti‐CarP+ subgroup as compared to ACPA−/anti‐CarP− RA patients and healthy controls; this was consistently found across the 6 sample collections. This association of HLA–DRB1*03 with ACPA−/anti‐CarP+ RA was independent of the presence of the shared allele (SE) and any other confounders analyzed. No other allele was specifically associated with the ACPA−/anti‐CarP+ RA patient subgroup. In contrast, frequency of the SE was significantly increased in the ACPA+/anti‐CarP− and ACPA+/anti‐CarP+ RA patient subgroups, without a significant distinction between them. Furthermore, some alleles (including HLA–DRB1*03) were associated with protection from ACPA+ RA. Conclusion: These findings indicate a specific association of HLA–DRB1*03 with ACPA−/anti‐CarP+ RA, suggesting that preferential presentation of carbamylated peptides could be a new mechanism underlying the contribution of HLA alleles to RA susceptibility. [ABSTRACT FROM AUTHOR]

Background: Ureteral stent and subcutaneous ureteral bypass (SUB) placement are commonly used for managing ureteral obstructions. Urinary tract infection (UTI) is a recognized complication. Objectives: To determine postoperative incidence of positive urine cultures in cats undergoing ureteral stent and SUB placement and to identify risk factors associated with positive urine cultures. Design Retrospective study. Animals Forty‐three cats that underwent 48 surgical events. Procedures: Medical records were reviewed. Cats were included if urine cultures were performed before and after surgery. Variables were compared to identify risk factors. Results: Urine cultures were positive postoperatively pre‐discharge in 5/20 (25%) cats. Median duration of follow‐up post‐discharge was 209 days (range, 11‐2184 days), with a total of 143 urine cultures performed in cats post‐discharge. Of these, 16 (11%) were positive in 12/48 (25%) cats. Nine different bacteria were identified; Enterococcus spp. (n = 8) predominated as monomicrobic or mixed infections. In 14/16 instances of positive urine cultures, affected cats had lower urinary tract signs, signs of pyelonephritis or both. Cats that received antibiotics postoperatively were significantly less likely to have a positive urine culture compared to those that did not (odds ratio, 0.2, 95% confidence interval, 0.05, 0.8, P = 0.02). Chronic kidney disease, renal implant type and postoperative urinary catheterization were not associated with positive urine cultures. Conclusions and Clinical Relevance: Postoperatively, occurrence of positive urine cultures was similar to previous reports. Subclinical bacteriuria was less common than UTI. Postoperative urinary catheterization has been speculated to increase risk of bacteriuria, but this was not the case in this cohort. [ABSTRACT FROM AUTHOR]

Modification of a Martius flap to treat rectovaginal fistulas consists of the transposition of a bulbocavernosus muscle flap between the vagina and rectal wall [[7]]. Rectovaginal fistula, defined as a communication between the rectum and the vagina [[1]], is mainly a clinical diagnosis [[1]]. [Extracted from the article]