The multiple actions of dipeptidyl peptidase 4 (DPP-4) and its pharmacological inhibition on bone metabolism: a review.

BACKGROUND: Dipeptidyl peptidase 4 (DPP-4) plays a crucial role in breaking down various substrates. It also has effects on the insulin signaling pathway, contributing to insulin resistance, and involvement in inflammatory processes like obesity and type 2 diabetes mellitus. Emerging effects of DPP-4 on bone metabolism include an inverse relationship between DPP-4 activity levels and bone mineral density, along with an increased risk of fractures. MAIN BODY: The influence of DPP-4 on bone metabolism occurs through two axes. The entero-endocrine-osseous axis involves gastrointestinal substrates for DPP-4, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptides 1 (GLP-1) and 2 (GLP-2). Studies suggest that supraphysiological doses of exogenous GLP-2 has a significant inhibitory effect on bone resorption, however the specific mechanism by which GLP-2 influences bone metabolism remains unknown. Of these, GIP stands out for its role in bone formation. Other gastrointestinal DPP-4 substrates are pancreatic peptide YY and neuropeptide Y-both bind to the same receptors and appear to increase bone resorption and decrease bone formation. Adipokines (e.g., leptin and adiponectin) are regulated by DPP-4 and may influence bone remodeling and energy metabolism in a paracrine manner. The pancreatic-endocrine-osseous axis involves a potential link between DPP-4, bone, and energy metabolism through the receptor activator of nuclear factor kappa B ligand (RANKL), which induces DPP-4 expression in osteoclasts, leading to decreased GLP-1 levels and increased blood glucose levels. Inhibitors of DPP-4 participate in the pancreatic-endocrine-osseous axis by increasing endogenous GLP-1. In addition to their glycemic effects, DPP-4 inhibitors have the potential to decrease bone resorption, increase bone formation, and reduce the incidence of osteoporosis and fractures. Still, many questions on the interactions between DPP-4 and bone remain unanswered, particularly regarding the effects of DPP-4 inhibition on the skeleton of older individuals. CONCLUSION: The elucidation of the intricate interactions and impact of DPP-4 on bone is paramount for a proper understanding of the body's mechanisms in regulating bone homeostasis and responses to internal stimuli. This understanding bears significant implications in the investigation of conditions like osteoporosis, in which disruptions to these signaling pathways occur. Further research is essential to uncover the full extent of DPP-4's effects on bone metabolism and energy regulation, paving the way for novel therapeutic interventions targeting these pathways, particularly in older individuals.

Sociodemographic disparities in oral health-related quality of life of schoolchildren in rural and urban areas.

OBJECTIVE: To assess the association between residence place, socioeconomic conditions and oral health-related quality of life (OHRQoL) among schoolchildren from southern Brazil. METHODS: Participants were 9-14-year-old schoolchildren from rural and urban municipal schools from Rosário do Sul, Brazil. The Child Perceptions Questionnaire (CPQ11-14) was used to assess OHRQoL. A structured questionnaire collected data on sociodemographic condition (family income), residence place (urban or rural), use of dental services, and behavioral variables. Clinical oral examination recorded the presence of missing teeth and the gingival bleeding index. Multilevel Poisson regression analysis with a hierarchical approach assessed the association between predictors and CPQ11-14 scores. Rate ratios (RR) and 95% confidence intervals (CI) were estimated. RESULTS: A total of 373 schoolchildren were included (rural area=122; urban area=251), with a mean CPQ11-14 score of 11.83, ranging from 0 to 42. Low-income schoolchildren living in rural areas had 15% higher CPQ11-14 scores than high-income schoolchildren living in urban areas. In urban areas, family income predicted OHRQoL, with low-income schoolchildren having 9% higher CPQ11-14 scores than high-income children. In rural areas, schoolchildren with low household income had 19% higher CPQ11-14 scores than high-income children. CONCLUSION: Schoolchildren from low-income families had a poorer OHRQoL irrespective of their area of residence (rural or urban). The association between family income and OHRQoL was more pronounced among children living in rural areas.

Contextuality and context-sensitivity in probabilistic models of cognition.

The context-sensitivity of cognition has been demonstrated across a wide range of cognitive functions such as perception, memory, judgement and decision making. A related term, 'contextuality', has appeared from the field of quantum cognition, with mounting empirical evidence demonstrating that cognitive phenomena are sometimes contextual. Contextuality is a subtle notion that influences how we must view the properties of the cognitive phenomenon being studied. This article addresses the questions: What does it mean for a cognitive phenomenon to be contextual? What are the implications of contextuality for probabilistic models of cognition? How does contextuality differ from context-sensitivity? Starting from George Boole's "conditions of possible experience", we argue that a probabilistic model of a cognitive phenomenon is necessarily subject to an assumption of realism. By this we mean that the phenomenon being studied is assumed to have cognitive properties with a definite value independent of observation. In contrast, quantum cognition holds that a cognitive property maybe indeterminate, i.e., its properties do not have well established values prior to observation. We argue that indeterminacy is sufficient for incompatibility between cognitive properties. In turn, incompatibility is necessary for their contextuality. The significance of this argument for cognitive psychology is the following:if a cognitive phenomenon is found to be contextual, then there is reason to believe it may be indeterminate. We illustrate by means of two crowdsourced experiments how context-sensitivity and contextuality of cognitive properties in the form of facial trait judgements can be characterized from empirical data. Finally, we conceptually and formally contrast contextuality with context-sensitivity. We propose that both involve a form of context dependence, with causality being the differentiating factor: the context dependence in context-sensitivity has a causal basis, whereas the context dependence in contextuality is acausal. The resulting implications for probabilistic models of cognition are discussed.

Semiquantitative analysis of interim 18F-FDG PET is superior in predicting outcome in Hodgkin lymphoma patients compared to visual analysis.

PURPOSE: To investigate the prognostic value of interim PET (PETi) in adult HL patients, comparing visual with semiquantitative analysis. MATERIAL AND METHODS: Retrospective analysis of Hodgkin's lymphoma (HL) patients diagnosed between 2012 and 2016 in the Onco-hematology Department of Instituto Português de Oncologia - Porto (median follow-up: 46.5 months [2.6-66.4]). Fifty-eight patients with available PET at diagnosis (PET0) and PETi data were included. PETi scans were analyzed according to Deauville 5-point scale (5-PS), and cut-off values for changes in maximum standardized uptake value [SUVmax], peak SUV [SUVpeak], metabolic tumour volume [MTV] and total lesion glycolysis index [TLG] between PETi and PET0 were computed using ROC analysis. Visual and semiquantitative data were compared with each other in the prediction of patient outcomes. RESULTS: Semiquantitative analysis obtained a higher sensitivity for persistent/relapsed disease compared to the 5-PS (70% vs. 10%, respectively), but lower specificity. It also demonstrated better predictive performance for response to first-line therapy (negative predictive value >92%). The positive predictive value was similar for all five measurements. At 60 months of follow-up, there was a significant difference between the progression free survival (PFS) curves of patients with positive and negative PETi according to ΔSUVmax (56.9% vs. 88.0%, p<0.05), ΔSUVpeak (55.9% vs. 88.1%, p<0.05), ΔMTV (35.3% vs. 88.7%, p<0.05), and ΔTLG (42.4% vs. 88.1%, p<0.05). Statistical significance was not reached when considering 5-PS results. DISCUSSION: PETi interpretation according to a semiquantitative approach appears to discriminate HL patients better than the visual 5-PS analysis. This could allow better detection of persistent or early relapsed disease, while a negative PETi result could support de-escalating therapy intensity.

Coleofasciculaceae, a Monophyletic Home for the Microcoleus steenstrupii Complex and Other Desiccation-tolerant Filamentous Cyanobacteria.

Cyanobacteria classified as Microcoleus steenstrupii play a significant role as pioneers of biological soil crusts (biocrusts), but this taxon is recognized to constitute a diverse complex of strains and field populations. With the aim of clarifying its systematics, we conducted a polyphasic characterization of this and allied taxa. A 16S ribosomal gene meta-analysis of published environmental sequences showed that the complex encompasses a variety of well supported genus-level clades with clade-specific environmental preferences, indicating significant niche differentiation. Fifteen strains in the M. steenstrupii complex were selected as representative of naturally occurring clades and studied using 16S rRNA gene phylogeny, morphology, and niche delineation with respect to temperature and rainfall. Bayesian phylogenetic reconstructions within a comprehensive, curated database of long 16S rRNA cyanobacterial sequences (1,000 base pairs or more) showed that they all belonged in a monophyletic, family-level clade (91.4% similarity) that included some other known genera of desiccation-resistant, largely terrestrial, filamentous, nonheterocystous cyanobacteria, including Coleofasciculus, the type genus for the family Coleofasciculaceae. To accommodate this biodiversity, we redescribe the Coleofasciculaceae, now composed of 11 genera, among which six are newly described herein (Funiculus, Parifilum, Arizonema, Crassifilum, Crustifilum, and Allocoleopsis), and five were previously recognized (Porphyrosiphon, Coleofasciculus, Pycnacronema, Potamolinea, and Wilmottia). We provide an evaluation of their respective niches and global distributions within biocrusts based on published molecular data. This new systematics treatment should help simplify and improve our understanding of the biology of terrestrial cyanobacteria.

Diagnostic, treatment, and follow-up of osteoporosis-position statement of the Latin American Federation of Endocrinology.

The Latin American Federation of Endocrinology position statement on osteoporosis was developed by endocrinologists from 9 countries. It encompasses the definition, diagnosis, treatment, and follow-up of the disease, the identification of barriers to healthcare, and proposals to improve the disease care in the region. INTRODUCTION: There is a gap in the understanding of osteoporosis in Latin America. The objective of this work is to state the position of the Latin American Federation of Endocrinology on osteoporosis care in postmenopausal women to better bridge this gap. METHODS: An experts' panel was formed comprising of 11 endocrinologists from 9 countries. A data search was conducted with a conceptual approach and data selection was based on the hierarchy of the EBHC pyramid. Unpublished data was considered for local epidemiological data and expert opinion for the identification of barriers to healthcare. An expert consensus based on the Delphi methodology was carried out. Experts were asked to respond on a 5-point Likert Scale to two provided answers to guiding questions. RESULTS: Consensus was agreed on the answer for the questions with the higher median on the Likert scale and synthetized on 16 statements covering the definition of osteoporosis, diagnostic approach, treatment options, and follow-up. Besides clinical topics, unmet needs in osteoporosis were identified in relation to local epidemiological data, barriers to treatment, and misclassification of programs within health systems. CONCLUSIONS: Through a process based on recognized methodological tools, FELAEN's position on osteoporosis was developed. This made it possible to state an optimum scenario for the care of the disease and helped to identify knowledge gaps. There is great variability in the approach to osteoporosis in Latin America and barriers in all the stages of healthcare persist.

Inactivation of Aspergillus species in real water matrices using medium pressure mercury lamps.

The aim of this work is to understand the inactivation efficiency of medium pressure mercury lamps, measured in terms of growth inhibition as well as cell death, damage and response, using three strains from three different Aspergillus species (A. fumigatus, A. niger and, A. terreus) spiked in filtered surface water. A complete characterization of the effect of the treatment on each strain of the fungal species was assessed considering spores' morphology, cell wall integrity and enzymatic activity, the formation of pyrimidine dimers in the DNA and proteome analysis. Results showed that, when subjected to medium pressure mercury lamps, A. niger is the most resistant to inactivation, that both A. fumigatus and A. niger suffer more morphological changes and present a higher number of damaged spores and A. terreus presented more dead spores. DNA damages detected in A. niger were able to be repaired to some extent, under both light and dark conditions. Finally, proteome analysis showed that the UV radiation treatment triggered different types of stress response, including cell wall reorganization and DNA repair in A. fumigatus and A. terreus, and oxidative stress responses like the increase in production of citric acid and itaconic acid in A. niger and A. terreus, respectively.

Pancreatic adenocarcinoma metastasis to the oral cavity: A rare case report and literature review.

A patient suffering from metastatic pancreatobiliary adenocarcinoma was referred to our hospital's stomatology department after a rapidly progressing swelling in the right mandibular angle, trismus and preauricular pain of 3-month duration. A mandible CT scan showed extensive bone rarefaction and a thickening of the contiguous soft tissues that involved the medial masseter and pterygoid muscle. The morphological findings and immunohistochemical profile were compatible with bone metastasis from pancreatic adenocarcinoma. Therefore, palliative treatment was proposed to the patient. Pancreatic cancer metastases to the oral cavity are extremely rare and characterized by its poor prognosis. Herein we describe the ninth case of metastatic spread to the jaw which is also remarkably the longest surviving reported case up to date.

Integrating a palliative approach into the healthcare provided by the French-African Pediatric Oncology Group's pilot units. Insights from a 3-year training program.

Working alongside local stakeholders, members of the French-African Pediatric Oncology Group developed a 3-year program to train pediatric oncology teams from 15 French-speaking countries in Africa in using analgesics and providing palliative care. This program was rolled out in three phases: initial training, in situ assessment, and advanced training in selected topics. To access this program, multidisciplinary teams had to come up with a project to improve their existing palliative care and pain management practices, and commit themselves to implementing it. All the teams invited agreed to take part in the program, which explicitly broached a subject that is often avoided in oncology teaching. The first phase was rolled out in 2017, with 65 trainees from 19 units attending one of three sessions held in Dakar, Senegal, Abidjan, Côte d'Ivoire, and Rabat, Morocco. The subsequent assessment revealed that only half the teams had started to implement their projects. The advanced training phase was therefore adjusted accordingly. A collective training session held in Marseille was attended by 15 trainees from seven teams whose projects were already underway, while in situ mentoring was provided for six other teams, through French-African twinnings in four cases. The length and openness of the program meant that we were able to identify and share the units' diverse realities, and fine-tune their projects accordingly, as well as plan ways of continuing the training both locally and collectively.

Bacillus toyonensis BCT-7112T transient supplementation improves vaccine efficacy in ewes vaccinated against Clostridium perfringens epsilon toxin.

AIM: The aim of the present study was to examine the vaccine immune response in ewes supplemented with Bacillus toyonensis BCT-7112T during a period of 5-day supplementation before vaccination against a recombinant Clostridium perfringens epsilon toxin (rETX). METHODS AND RESULTS: Ewes were vaccinated with 200 µg of rETX adjuvanted with 10% aluminium hydroxide. The treat group was orally supplemented with B. toyonensis BCT-7112T (3 × 108 viable spores) for 5 days prior to the first and second vaccination. Ewes supplemented with B. toyonensis BCT-7112T showed higher neutralizing antibody titres than the non-supplemented ewes (P < 0·05), with an increase in serum levels for total IgG anti-rETX by 3·2-fold (P < 0·0001), and for both IgG isotypes IgG1 and IgG2 by 2·1-fold and 2·3-fold (P < 0·01), respectively, compared with the control group. The peripheral blood mononuclear cells of ewes in the supplemented group had a higher (P < 0·05) cytokine mRNA transcription levels for IL-2 (6·4-fold increase), IFN-γ (2·9-fold increase) and transcription factor Bcl6 (2·3-fold increase) compared with the control group. CONCLUSION: We conclude that a 5 days of supplementation with B. toyonensis BCT-7112T prior vaccination is sufficient to significantly improve the humoral immune response of ewes against C. perfringens recombinant ETX vaccine. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings open a new perspective in the utilization of B. toyonensis BCT-7112T as an immunomodulator since a 5 days period of probiotic supplementation is sufficient to improve the vaccine immune response.

Sarcopenia in Type 2 Diabetes Mellitus: A Cross-Sectional Observational Study.

BACKGROUND: The aim of this study was to compare the prevalence of low muscle mass and sarcopenia in patients with type 2 diabetes mellitus (T2DM) versus paired controls (control group, CG) and the association between sarcopenia and chronic diabetes complications. METHODS: Men and women ≥50 years with T2DM (T2DM group, T2DMG) were recruited during routine outpatient visits. Total body densitometry and handgrip strength (HGS) were evaluated in the T2DMG and CG, while the T2DMG was also evaluated for the physical performance using the gait speed (GS) test. Sarcopenia was diagnosed according to the criteria of the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). RESULTS: The study included 177 individuals in the T2DMG and 146 in the CG. The mean HGS value was lower in the T2DMG (24.4 ± 10.3 kg) compared with the CG (30.9 ± 9.15 kg), p < 0.001, with low HGS in 46 (25.9%) and 10 (9%) in the T2DMG and CG, respectively (p < 0.001). The prevalence of sarcopenia defined according to the FNIH criteria was higher in the T2DMG 23 (12.9%) compared with the CG 8 (5.4%), p < 0.03. The presence of albuminuria increased the odds of sarcopenia (odds ratio (OR) 2.84, 95% confidence interval (CI) 1.07-7.68, p=0.04) and osteoporosis (OR 3.38, 95% CI 1.12-9.89, p=0.03), even in patients with mild to moderate nephropathy. The body composition analysis showed increased odds of sarcopenia with increased percentage of total fat (%TF) in women (OR 1.18, 95% CI, 1.03-1.43, p=0.03) and men (OR 1.31, 95% CI, 1.10-1.75, p=0.01). CONCLUSION: Patients with T2DM presenting with albuminuria, osteoporosis, and increased %TF were more likely to have sarcopenia. This finding emphasizes the need for patients with T2DM to be evaluated for sarcopenia to allow for early implementation of measures to prevent or treat this disorder.

Dyadic Adjustment and Sexual Satisfaction in HPV Diagnosed Portuguese Women: A Longitudinal Study.

This study examined the relationship between dyadic adjustment and sexual satisfaction, in Portuguese women diagnosed with human papillomavirus (HPV), using a 1-year longitudinal design. Women were assessed at the beginning of the study (N = 209), six months after (N = 178) and twelve months later (N = 105). A better dyadic adjustment predicted more sexual satisfaction but the inverse was not observed. Younger women (< 40 years) showed greater difficulties in dyadic adjustment, while older women (> 40 years) reported lower sexual satisfaction. Findings highlight the importance of intervening with couples, using different intervention programs according to women's age.

Impact of markers of endothelial injury and hypercoagulability on systemic lupus erythematosus.

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.

Influence of volumetric loading rate on aerobic sewage treatment for indigenous algal growth.

Many rural areas of Latin America and the Caribbean (LAC) region are economically depressed. Rural sewage treatment in most areas of LAC is deficient or non-existent. Consequently, the possibility of generating economic revenue from treated sewage is an attractive option for deprived areas of developing countries. Given its peculiar characteristics, rural sewage may be coupled with biological systems such as algae for nutrient cycling. Acceptable algae growth and nutrient elimination were obtained from rural sewage whose treatment may have fallen short of current disposal standards. In this study, aerobic systems working on an 8-month cycle at three different volumetric loading rates (Bv) were assessed in relation to the lifetime growth of three algae strains native to Ecuador. Results indicate Chlorella sp. M2 as the optimal algal strain, with the highest growth rate at Bv of 1 g COD L-1 d- 1 and a removal of organic-N (30%), PO4 3--P (87%) and NH4 +-N (95%). Concomitantly, the kinetic constants of the sewage resulted in a low biomass yield coefficient, making the proposed system highly suitable for developing countries. Finally, the proposed partial recovery stream method, combining nutrient recovery with economic resource generation, appears to contain great potential.

A comprehensive study on crystal structure of a novel sulfonamide-dihydroquinolinone through experimental and theoretical approaches.

Quinolinones and sulfonamides are moieties with biological potential that can be linked to form new hybrid compounds with improved potential. However, there are few hybrids of these molecules reported. In this sense, this work presents a structural description of a new sulfonamide-dihydroquinolinone (E)-2-(2-methoxyphenyl)-3-(3-nitrobenzylidene)-1-(phenylsulfonyl)-2,3 dihydroquinolin-4(1H)-one (DHQ). The molecular structure of DHQ was elucidated by X-ray diffraction, nuclear magnetic resonance and infrared spectroscopy, and both molecular packing and intermolecular interactions were analyzed by Hirshfeld surfaces and fingerprint maps. In addition, theoretical calculations on frontier orbitals, molecular electrostatic potential maps, and assignments were performed. The crystal packing of DHQ was found to be stabilized by a dimer through a weak C-H⋯O interaction along the c axis. Moreover, the structure is stabilized mainly by C-H⋯O and C-H⋯π interactions, since the interaction C25-H25⋯π contributes to a chain formation. The Hirshfeld normalized surface shows that the closest interactions are around the atoms linked to the dimer formation. The calculations indicate that DHQ possesses electrophilic sites near O atoms and depleted electrons around the H atoms. There is a band GAP of 3.29 eV between its frontier orbitals, which indicates that DHQ is more reactive than other analogues published.

Associations between anthropometric indicators in early life and low-grade inflammation, insulin resistance and lipid profile in adolescence.

BACKGROUND AND AIMS: The long-term relations between excessive adiposity in early childhood and unfavourable cardiometabolic profiles in later ages are not yet completely understood. We aimed to assess the associations between birth weight (BW) and BMI from 6 months to 6 years of age, with biomarkers indicative of low-grade inflammation, insulin resistance and lipid profiles in adolescence. METHODS AND RESULTS: Retrospective school-based study with 415 Portuguese adolescents (220 girls), mean age of 14.08 ± 1.6 years old. Anthropometric data from birth to 6 years old was extracted from individual child health book records. Actual weight and height were measured and BMI calculated. Participants were classified at each time point as normal weight or overweight according to WHO reference values. Biomarkers were obtained from venous blood samples. Linear regressions were used to explore the associations between the biomarkers and early life anthropometric indicators. From 2 years onwards, BMI associated positively with the inflammatory score and HOMA-IR in adolescence. Children who were overweight/obese from 2 to 6 years of age presented significantly higher inflammatory score and HOMA-IR later in adolescence. TC/HDL ratio was also positively associated with BMI from the age of 5 years onwards. The associations between BMI and cardiometabolic outcomes remained positive in adolescence, with overweight adolescents presenting a higher inflammatory score, HOMA-IR and TC/HDL than normal weight adolescents. CONCLUSION: A high BMI from an early age was consistently associated with worse inflammatory and lipid profiles and insulin resistance in adolescence. No associations were found between BW and the same studied outcomes.

Reduction of scum production in a modified UASB reactor treating domestic sewage.

The scum accumulation inside gas-solid-liquid separators (GSL) is one of the main limitations of upflow anaerobic sequencing batch (UASB) reactors during treatment of domestic sewage. Although this type of reactor can be equipped with devices that periodically remove scum, this solution has been proved to be very expensive in addition to being inefficient when discharging procedures are not correctly performed. The main goal of this study was to investigate the performance of a modified UASB reactor concept with a GSL separator which promotes continuous scum discharge to the settling compartment. Furthermore, this proposal was compared with a conventional UASB reactor which was used as control. Both reactors in demo-scale were fed with domestic wastewater and scum production was measured. The results demonstrated volumetric reduction of 50%, and 75% reduction in the mass of total solids in the modified reactor. Additionally, the amount of biogas recovered from the modified reactor was higher than the amount that the control reactor recovered. Therefore, the proposed modification has been proved to be effective, bringing new possibilities to the GSL project.