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The hip capsule and capsular ligaments play crucial roles in providing hip stability and mobility. Their role in hip pathologies is being increasingly recognized, underscoring the need for thorough imaging evaluation, which is better performed through MRI-arthrography. Various diseases affect the hip capsule directly or indirectly. Improper mechanical loading, as seen in conditions such as femoroacetabular impingement or chondrolabral pathology, can induce capsule thickening, whereas thinning and laxity of the capsule are characteristics of microinstability. Inflammatory conditions, including adhesive capsulitis of the hip, crystal deposition disease, polymyalgia rheumatica, and infections, also lead to capsular changes. Traumatic events, particularly posterior hip dislocations, cause capsule ligament disruption and may lead to hip macroinstability. Friction syndromes can lead to capsular edema due to impingement of the adjacent capsule. Hip arthroscopy can result in various postoperative findings ranging from fibrotic adhesions to focal or extensive capsule discontinuation. Although the significance of hip capsule thickness and morphology in the pathogenesis of hip diseases remains unclear, radiologists must recognize capsule alterations on imaging evaluation. These insights can aid clinicians in accurately diagnosing and effectively managing patients with hip conditions.

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Graphene is a promising biomaterial. However, its dispersion in aqueous medium is challenging. This study aimed to modify graphene nanoparticles with L-dopa to improve the properties of experimental dental adhesives. Adhesives were formulated with 0% (control), 0.25%, 0.5%, and 0.75% of graphene, modified or not. Particle modification and dispersion were microscopically assessed. Degree of conversion was tested by Fourier-transform infrared spectroscopy. Flexural strength and modulus of elasticity were evaluated by a 3-point flexural test. Bond strength was tested by shear. To test water sorption/solubility, samples were weighed during hydration and dehydration. Antibacterial activity was tested by Streptococcus mutans colony-forming units quantification. Cytotoxicity on fibroblasts was evaluated through a dentin barrier test. The modification of graphene improved the particle dispersion. Control presented the highest degree of conversion, flexural strength, and bond strength. In degree of conversion, 0.25% of groups were similar to control. In bond strength, groups of graphene modified by L-dopa were similar to Control. The modulus of elasticity was similar between groups. Cytotoxicity and water sorption/solubility decreased as particles increased. Compared to graphene, less graphene modified by L-dopa was needed to promote antibacterial activity. By modifying graphene with L-dopa, the properties of graphene and, therefore, the adhesives incorporated by it were enhanced.

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Objective: To describe the accuracy of HealthVCF, a software product that uses artificial intelligence, in the detection of incidental moderate-to-severe vertebral compression fractures (VCFs) on chest and abdominal computed tomography scans. Materials and Methods: We included a consecutive sample of 899 chest and abdominal computed tomography scans of patients 51-99 years of age. Scans were retrospectively evaluated by the software and by two specialists in musculoskeletal imaging for the presence of VCFs with vertebral body height loss > 25%. We compared the software analysis with that of a general radiologist, using the evaluation of the two specialists as the reference. Results: The software showed a diagnostic accuracy of 89.6% (95% CI: 87.4-91.5%) for moderate-to-severe VCFs, with a sensitivity of 73.8%, a specificity of 92.7%, and a negative predictive value of 94.8%. Among the 145 positive scans detected by the software, the general radiologist failed to report the fractures in 62 (42.8%), and the algorithm detected additional fractures in 38 of those scans. Conclusion: The software has good accuracy for the detection of moderate-to-severe VCFs, with high specificity, and can increase the opportunistic detection rate of VCFs by radiologists who do not specialize in musculoskeletal imaging.

Objetivo: Descrever a acurácia do software HealthVCF na detecção incidental de fraturas compressivas de corpos vertebrais moderadas a graves em exames de tomografia computadorizada do tórax e abdome. Materiais e Métodos: Foram incluídos 899 exames consecutivos de pacientes com idades entre 51 e 99 anos. As imagens foram retrospectivamente avaliadas pelo software e por dois radiologistas especializados em musculoesquelético que investigaram fraturas compressivas de corpos vertebrais com perda da altura somática > 25%. A análise comparativa foi realizada entre o software e um radiologista geral, usando a avaliação do especialista como referência. Resultados: O software apresentou uma acurácia de 89,6% (IC 95%: 87,4­91,5%) para fraturas compressivas moderadas a graves, com sensibilidade de 73,8%, especificidade de 92,7% e valor preditivo negativo de 94,8%. Entre as 145 tomografias positivas detectadas pelo software, o radiologista geral deixou de relatar as fraturas em 62 (42,8%) e o algoritmo detectou fraturas adicionais em 38 dessas tomografias. Conclusão: O software possui boa acurácia na detecção de fraturas compressivas moderadas a graves, com alta especificidade, podendo aumentar a taxa de detecção oportunística dessas fraturas por radiologistas não especializados em musculoesquelético.

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BACKGROUND: Idiopathic juvenile osteoporosis (IJO) is a rare condition characterized by low bone mass that can increase the risk of fractures in children. Treatment options for these patients are limited as the molecular mechanisms of disease initiation and progression are incompletely understood. Sclerostin inhibits canonical Wnt signaling, which is important for the bone formation activity of osteoblasts, and elevated sclerostin has been implicated in adult osteoporosis. OBJECTIVE: To evaluate the role of sclerostin in IJO, high-resolution confocal microscopy analyses were performed on bone biopsies collected from 13 pediatric patients. METHODS: Bone biopsies were stained with sclerostin, and ß-catenin antibodies showed elevated expression across osteocytes and increased sclerostin-positive osteocytes in 8 of the 13 total IJO patients (62%). RESULTS: Skeletal sclerostin was associated with static and dynamic histomorphometric parameters. Further, colocalization analyses showed that bone sclerostin colocalized with phosphorylated ß-catenin, a hallmark of Wnt signaling that indicates Wnt inhibition. In contrast, sclerostin-positive osteocytes were not colocalized with an "active" unphosphorylated form of ß-catenin. CONCLUSIONS: These results support a model that altered levels of sclerostin and Wnt signaling activity occur in IJO patients.

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Objective: This multicenter study aimed to retrospectively evaluate the impact of high boost simultaneous integrated boost (SIB) to pathologic lymph nodes compared to Sequential boost (Seq) in patients with locally advanced cervical cancer (LACC). Materials and methods: 97 patients with pelvic and/or para-aortic (PAo) node-positive LACC treated by definitive chemoradiation were included. Two groups were analyzed: Sequential boost group and simultaneous integrated boost (SIB) group. Endpoints were Distant Recurrence Free Survival (DRFS), Recurrence Free Survival (RFS), Overall Survival (OS), locoregional pelvic and PAo control and toxicities. Results: 3-years DRFS in SIB and Seq groups was 65% and 31% respectively (log-rank p < 0.001). 3-years RFS was 58% and 26% respectively (log-rank p = 0.009). DRFS prognostic factors in multivariable analysis were SIB, PAo involvement and maximum pelvic node diameter ≥ 2cm. Adenocarcinoma histology and absence of brachytherapy tended to be prognostic factors. SIB provided the best pelvic control at first imaging with 97%. There was no significant difference in terms of toxicities between groups. Conclusions: Nodal SIB seems to be unavoidable in the treatment of node-positive LACC. It provides the best DRFS, RFS and pelvic control without additional toxicity, with a shortened treatment duration.

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BACKGROUND: cardiorespiratory arrest (CRA) is a severe public health concern, and clinical simulation has proven to be a beneficial educational strategy for training on this topic. OBJECTIVE: To describe the implementation of a program for pediatric cardiac arrest care using rapid-cycle deliberate practice (RCDP), the quality of the technique employed, and participants' opinions on the methodology. DESIGN AND SETTING: This descriptive cross-sectional study of pre- and post-performance training in cardiopul monary resuscitation (CPR) techniques and reaction evaluation was conducted in a hospital in São Paulo. METHODS: Multidisciplinary groups performed pediatric resuscitation in a simulated scenario with RCDP mediated by a facilitator. The study sample included professionals working in patient care. During the simulation, the participants were evaluated for their compliance with the CRA care algorithm. Further, their execution of chest compressions was assessed pre- and post-intervention. RESULTS: In total, 302 professionals were trained in this study. The overall quality of CPR measured pre-intervention was inadequate, and only 26% had adequate technique proficiency, whereas it was 91% (P < 0.01) post-intervention. Of the participants, 95.7% responded to the final evaluation and provided positive comments on the method and their satisfaction with the novel simulation. Of these, 88% considered that repetition of the technique used was more effective than traditional simulation. CONCLUSIONS: The RCDP is effective for training multidisciplinary teams in pediatric CPR, with an emphasis on the quality of chest compressions. However, further studies are necessary to explore whether this trend translates to differential performances in practical settings.

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AIMS: We developed three new analogs of the antimicrobial peptide (AMP) Citropin 1.1: DAN-1-13, AJP-1-1, and HHX-2-28, and tested their potential antimicrobial and antibiofilm activities against Staphylococcus aureus and S. pseudintermedius. Potential cytotoxic or hemolytic effects were determined using cultured human keratinocytes and erythrocytes to determine their safety. METHODS AND RESULTS: To assess the antimicrobial activity of each compound, minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined against methicillin-resistant and methicillin-susceptible strains of S. aureus and S. pseudintermedius. Activity against newly formed and mature biofilms was determined in two clinical isolates using spectrophotometry and scanning electron microscopy (SEM). All three compounds exhibited antimicrobial and bactericidal activity against all studied S. aureus and S. pseudintermedius strains, with MICs ranging from 4-32 µg ml-1 and MBCs ranging from 8-128 µg ml-1. Subinhibitory concentrations of all compounds also showed ant-biofilm activity in the two tested isolates. All compounds exhibited limited cytotoxic and hemolytic activity. CONCLUSIONS: Novel analogs of Citropin 1.1 exhibit antimicrobial and bactericidal activities against S. aureus and S. pseudintermedius isolates and inhibit the biofilm formation of these bacteria.

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Maturation defects are intrinsic features of osteoblast lineage cells in CKD patients. These defects persist ex vivo, suggesting that CKD induces epigenetic changes in bone cells. To gain insights into which signaling pathways contribute to CKD-mediated, epigenetically driven, impairments in osteoblast maturation, we characterized RNA expression and DNA methylation patterns by RNA-Seq and MethylationEpic in primary osteoblasts from nine adolescent and young adult dialysis patients with end-stage kidney disease and three healthy references. ATAC-Seq was also performed on a subset of osteoblasts. Bone matrix protein expression was extracted from the iliac crest and evaluated by proteomics. Gene set enrichment analysis was used to establish signaling pathways consistently altered in chromatin accessibility, DNA methylation, and RNA expression patterns. Single genes were suppressed in primary osteoblasts using shRNA and mineralization characterized in vitro. The effect of nuclear factor of activated T cells (NFAT) signaling suppression was also assessed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) incorporation. We found that signaling pathways critical for osteoblast differentiation were strongly downregulated in CKD osteoblasts. Gene set enrichment analysis identified highly significant methylation changes, differential chromatin accessibility, and altered RNA expression in NFAT signaling targets. NFAT inhibition reduced osteoblast proliferation. Combined analysis of osteoblast RNA expression and whole bone matrix composition identified 13 potential ligand-receptor pairs. In summary, epigenetic changes in CKD osteoblasts associate with altered expression of multiple osteoblast genes and signaling pathways. An increase in NFAT signaling may play a role in impaired CKD osteoblast maturation. Epigenetic changes also associate with an altered bone matrix, which may contribute to bone fragility. Further studies are necessary to elucidate the pathways affected by these genetic alterations since elucidating these pathways will be vital to correcting the underlying biology of bone disease in the CKD population.

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BACKGROUND: Important evidence has been constantly produced and needs to be converted into practice. Professional consumption of such evidence may be a barrier to its implementation. Then, effective implementation of evidence-based interventions in clinical practice leans on the understanding of how professionals value attributes when choosing between options for dental care, permitting to guide this implementation process by maximizing strengthens and minimizing barriers related to that. METHODS: This is part of a broader project investigating the potential of incorporating scientific evidence into clinical practice and public policy recommendations and guidelines, identifying strengths and barriers in such an implementation process. The present research protocol comprises a Discrete Choice Experiment (DCE) from the Brazilian oral health professionals' perspective, aiming to assess how different factors are associated with professional decision-making in dental care, including the role of scientific evidence. Different choice sets will be developed, either focusing on understanding the role of scientific evidence in the professional decision-making process or on understanding specific attributes associated with different interventions recently tested in randomized clinical trials and available as newly produced scientific evidence to be used in clinical practice. DISCUSSION: Translating research into practice usually requires time and effort. Shortening this process may be useful for faster incorporation into clinical practice and beneficial to the population. Understanding the context and professionals' decision-making preferences is crucial to designing more effective implementation and/or educational initiatives. Ultimately, we expect to design an efficient implementation strategy that overcomes threats and potential opportunities identified during the DCEs, creating a customized structure for dental professionals. TRIAL REGISTRATION: https://osf.io/bhncv .

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Mitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are protein- and lipid-enriched hubs that mediate interorganellar communication by contributing to the dynamic transfer of Ca2+, lipid, and other metabolites between these organelles. Defective MERCs are associated with cellular oxidative stress, neurodegenerative disease, and cardiac and skeletal muscle pathology via mechanisms that are poorly understood. We previously demonstrated that skeletal muscle-specific knockdown (KD) of the mitochondrial fusion mediator optic atrophy 1 (OPA1) induced ER stress and correlated with an induction of Mitofusin-2, a known MERC protein. In the present study, we tested the hypothesis that Opa1 downregulation in skeletal muscle cells alters MERC formation by evaluating multiple myocyte systems, including from mice and Drosophila, and in primary myotubes. Our results revealed that OPA1 deficiency induced tighter and more frequent MERCs in concert with a greater abundance of MERC proteins involved in calcium exchange. Additionally, loss of OPA1 increased the expression of activating transcription factor 4 (ATF4), an integrated stress response (ISR) pathway effector. Reducing Atf4 expression prevented the OPA1-loss-induced tightening of MERC structures. OPA1 reduction was associated with decreased mitochondrial and sarcoplasmic reticulum, a specialized form of ER, calcium, which was reversed following ATF4 repression. These data suggest that mitochondrial stress, induced by OPA1 deficiency, regulates skeletal muscle MERC formation in an ATF4-dependent manner.

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Mitochondria undergo repeated cycles of fusion and fission that regulate their size and shape by a process known as mitochondrial dynamics. Numerous studies have revealed the importance of this process in maintaining mitochondrial health and cellular homeostasis, particularly in highly metabolically active tissues such as skeletal muscle and the heart. Here, we review the literature on the relationship between mitochondrial dynamics and the pathophysiology of type 2 diabetes and cardiovascular disease (CVD). Importantly, we emphasize divergent outcomes resulting from downregulating distinct mitochondrial dynamics proteins in various tissues. This review underscores compensatory mechanisms and adaptive pathways that offset potentially detrimental effects, resulting instead in improved metabolic health. Finally, we offer a perspective on potential therapeutic implications of modulating mitochondrial dynamics proteins for treatment of diabetes and CVD.

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In brown adipose tissue (BAT), short-term cold exposure induces the activating transcription factor 4 (ATF4), and its downstream target fibroblast growth factor 21 (FGF21). Induction of ATF4 in BAT in response to mitochondrial stress is required for thermoregulation, partially by increasing FGF21 expression. In the present study, we tested the hypothesis that Atf4 and Fgf21 induction in BAT are both required for BAT thermogenesis under physiological stress by generating mice selectively lacking either Atf4 (ATF4 BKO) or Fgf21 (FGF21 BKO) in UCP1-expressing adipocytes. After 3 days of cold exposure, core body temperature was significantly reduced in ad-libitum-fed ATF4 BKO mice, which correlated with Fgf21 downregulation in brown and beige adipocytes, and impaired browning of white adipose tissue. Conversely, despite having reduced browning, FGF21 BKO mice had preserved core body temperature after cold exposure. Mechanistically, ATF4, but not FGF21, regulates amino acid import and metabolism in response to cold, likely contributing to BAT thermogenic capacity under ad libitum-fed conditions. Importantly, under fasting conditions, both ATF4 and FGF21 were required for thermogenesis in cold-exposed mice. Thus, ATF4 regulates BAT thermogenesis under fed conditions likely in a FGF21-independent manner, in part via increased amino acid uptake and metabolism.

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INTRODUCTION: Post-operative pain is the most prevalent type of acute pain. Nurses are the health care professionals who most frequently assess pain, as well as evaluating the patient's response to pain management treatment and monitoring for the occurrence of adverse events. Thus, to improve outcomes and quality of care, the interventions used by nurses should be based on best practices. OBJECTIVES: The aim of this project was to implement best practices in post-operative pain management in an intensive care unit. METHODS: This evidence implementation project was conducted in a hospital for the surgical treatment of orthopedic diseases and trauma. The project followed the JBI evidence implementation framework. The project used JBI PACES software as well as JBI's Getting Research into Practice (GRiP) audit and feedback tools to develop eight audit criteria for the baseline and follow-up audits. RESULTS: The baseline audit showed that criteria 3 and 6 had low compliance, with few patients having documented plans and goals, and receiving multimodal analgesia in the ICU, respectively. Criteria 7 and 8, which assessed the use of opioids and follow-up by a pain specialist, revealed compliance of 60% and 50%, respectively. Criterion 3 improved from 0% to 20%. Criteria 6, 7, and 8 also improved, rising to 30%, 22.8%, and 50%, respectively. CONCLUSION: The project improved compliance with best practices in post-operative pain management. Further studies are needed to ensure the project's long-term sustainability.

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OBJETIVO: mapear na literatura os cuidados de enfermagem antes, durante e após a sangria terapêutica em pessoa idosa. MÉTODO: esta revisão será conduzida conforme o Manual do Instituto Joanna Briggs com utilização das diretrizes do checklist PRISMA Extension for Scoping Reviews, utilizando as seguintes bases de dados: MEDLINE via PubMed, Web of Science, EMBASE, COCHRANE e, para a literatura cinzenta, Catálogo de Teses e Dissertações CAPES e o Google Scholar. Após a busca dos estudos, será feita remoção das duplicadas no gerenciador EndNote e, em seguida, serão exportadas para o software Rayyan onde serão analisados os títulos e resumos seguida da leitura do texto completo por pares e às cegas, e quaisquer desacordos serão discutidos com um terceiro revisor. Os dados extraídos serão apresentados por meio de fluxogramas, tabelas, quadros e discussão narrativa e descritiva. Será realizado o registro da revisão no Open Science Framework: https://doi.org/10.17605/OSF.IO/HS2EK.

OBJECTIVE: To map in the literature nursing care before, during, and after therapeutic bleeding in the elderly. METHOD: this review will be conducted by the Joanna Briggs Institute Manual using the PRISMA Extension for Scoping Reviews CHECKLIST guidelines using the following databases: MEDLINE via PubMed, Web of Science, EMBASE, COCHRANE and, for gray literature, Catalogue of theses and dissertations CAPES and Google Scholar. After searching the studies, the duplicates will be removed in the EndNote manager and then exported to the Rayyan software where the titles and abstracts will be analyzed followed by reading the full text by pairs and blind, and any disagreements will be discussed with a third reviewer. The extracted data will be presented through flowcharts, tables, and narrative and descriptive discussion. The review will be recorded in the Open Science Framework: https://doi.org/10.17605/OSF.IO/HS2EK.

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BACKGROUND: The stingless bee, Trigona spinipes, is an important pollinator of numerous native and cultivated plants. Trigona spinipes populations can be negatively impacted by insecticides commonly used for pest control in crops. However, this species has been neglected in toxicological studies. Here we observed the effects of seven insecticides on the survival of bees that had fed directly on insecticide-contaminated food sources or received insecticides via trophallactic exchanges between nestmates. The effects of insecticides on flight behavior were also determined for the compounds considered to be of low toxicity. RESULTS: Imidacloprid, spinosad and malathion were categorized as highly toxic to T. spinipes, whereas lambda-cyhalothrin, methomyl and chlorfenapyr were of medium to low toxicity and interfered with two aspects of flight behavior evaluated here. Chlorantraniliprole was the only insecticide tested here that had no significant effect on T. spinipes survival, although it did interfere with one aspect of flight capacity. A single bee that had ingested malathion, spinosad or imidacloprid, could contaminate three, four and nineteen other bees, respectively via trophallaxis, resulting in the death of the recipients. CONCLUSION: This is the first study to evaluate the ecotoxicology of a range of insecticides that not only negatively affected T. spinipes survival, but also interfered with flight capacity, a very important aspect of pollination behavior. The toxicity of the insecticides was observed following direct ingestion and also via trophallactic exchanges between nestmates, highlighting the possibility of lethal effects of these insecticides spreading throughout the colony, reducing the survival of non-foraging individuals. © 2023 Society of Chemical Industry.

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ABSTRACT BACKGROUND: cardiorespiratory arrest (CRA) is a severe public health concern, and clinical simulation has proven to be a beneficial educational strategy for training on this topic. OBJECTIVE: To describe the implementation of a program for pediatric cardiac arrest care using rapid-cycle deliberate practice (RCDP), the quality of the technique employed, and participants' opinions on the methodology. DESIGN AND SETTING: This descriptive cross-sectional study of pre- and post-performance training in cardiopul monary resuscitation (CPR) techniques and reaction evaluation was conducted in a hospital in São Paulo. METHODS: Multidisciplinary groups performed pediatric resuscitation in a simulated scenario with RCDP mediated by a facilitator. The study sample included professionals working in patient care. During the simulation, the participants were evaluated for their compliance with the CRA care algorithm. Further, their execution of chest compressions was assessed pre- and post-intervention. RESULTS: In total, 302 professionals were trained in this study. The overall quality of CPR measured pre-intervention was inadequate, and only 26% had adequate technique proficiency, whereas it was 91% (P < 0.01) post-intervention. Of the participants, 95.7% responded to the final evaluation and provided positive comments on the method and their satisfaction with the novel simulation. Of these, 88% considered that repetition of the technique used was more effective than traditional simulation. CONCLUSIONS: The RCDP is effective for training multidisciplinary teams in pediatric CPR, with an emphasis on the quality of chest compressions. However, further studies are necessary to explore whether this trend translates to differential performances in practical settings.

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Abstract Objective: To describe the accuracy of HealthVCF, a software product that uses artificial intelligence, in the detection of incidental moderate-to-severe vertebral compression fractures (VCFs) on chest and abdominal computed tomography scans. Materials and Methods: We included a consecutive sample of 899 chest and abdominal computed tomography scans of patients 51-99 years of age. Scans were retrospectively evaluated by the software and by two specialists in musculoskeletal imaging for the presence of VCFs with vertebral body height loss > 25%. We compared the software analysis with that of a general radiologist, using the evaluation of the two specialists as the reference. Results: The software showed a diagnostic accuracy of 89.6% (95% CI: 87.4-91.5%) for moderate-to-severe VCFs, with a sensitivity of 73.8%, a specificity of 92.7%, and a negative predictive value of 94.8%. Among the 145 positive scans detected by the software, the general radiologist failed to report the fractures in 62 (42.8%), and the algorithm detected additional fractures in 38 of those scans. Conclusion: The software has good accuracy for the detection of moderate-to-severe VCFs, with high specificity, and can increase the opportunistic detection rate of VCFs by radiologists who do not specialize in musculoskeletal imaging.

Resumo Objetivo: Descrever a acurácia do software HealthVCF na detecção incidental de fraturas compressivas de corpos vertebrais moderadas a graves em exames de tomografia computadorizada do tórax e abdome. Materiais e Métodos: Foram incluídos 899 exames consecutivos de pacientes com idades entre 51 e 99 anos. As imagens foram retrospectivamente avaliadas pelo software e por dois radiologistas especializados em musculoesquelético que investigaram fraturas compressivas de corpos vertebrais com perda da altura somática > 25%. A análise comparativa foi realizada entre o software e um radiologista geral, usando a avaliação do especialista como referência. Resultados: O software apresentou uma acurácia de 89,6% (IC 95%: 87,4-91,5%) para fraturas compressivas moderadas a graves, com sensibilidade de 73,8%, especificidade de 92,7% e valor preditivo negativo de 94,8%. Entre as 145 tomografias positivas detectadas pelo software, o radiologista geral deixou de relatar as fraturas em 62 (42,8%) e o algoritmo detectou fraturas adicionais em 38 dessas tomografias. Conclusão: O software possui boa acurácia na detecção de fraturas compressivas moderadas a graves, com alta especificidade, podendo aumentar a taxa de detecção oportunística dessas fraturas por radiologistas não especializados em musculoesquelético.

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BACKGROUND: Obesity is a worldwide concern due to its global rapid expansion and remarkable impact on individual's health by predisposing to several other diseases. About twice as many women as men suffer from severe obesity and, in fact, there are stages in a woman's life when weight gain and adiposity can result in greater damage to health. For example, obesity triples the chance of a woman developing gestational diabetes. Many hormones promote the metabolic adaptations of pregnancy, including progesterone, whose role in female obesity is still not well known despite being involved in many physiological and pathological processes. METHODS: Here we investigated whether progesterone treatment at low dose can worsen the glucose metabolism and the morpho functional aspects of adipose tissue and pancreas in obese females. Mice were assigned into four groups: normocaloric diet control (NO-CO), high-fat and -fructose diet control (HFF-CO), normocaloric diet plus progesterone (NO-PG) and high-fat and -fructose diet plus progesterone (HFF-PG) for 10 weeks. Infusion of progesterone (0.25 mg/kg/day) was done by osmotic minipump in the last 21 days of protocol. RESULTS: Animals fed a hypercaloric diet exhibited obesity with increased body weight (p < 0.0001), adipocyte hypertrophy (p < 0.0001), hyperglycemia (p = 0.03), and glucose intolerance (p = 0.001). HFF-CO and HFF-PG groups showed lower adiponectin concentration (p < 0.0001) and glucose-stimulated insulin secretion (p = 0.03), without differences in islet size. Progesterone attenuated glucose intolerance in the HFF-PG group (p = 0.03), however, did not change morphology or endocrine function of adipose tissue and pancreatic islets. CONCLUSIONS: Taken together, our results showed that low dose of progesterone does not worsen the effects of hypercaloric diet in glycemic metabolism, morphology and function of adipose tissue and pancreatic islets in female animals. These results may improve the understanding of the mechanisms underlying the pathogenesis of obesity in women and eventually open new avenues for therapeutic strategies and better comprehension of the interactions between progesterone effects and obesity.

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The pathophysiology of chronic kidney disease-mineral and bone disorder (CKD-MBD) is not well understood. Specific factors secreted by osteocytes are elevated in the serum of adults and pediatric patients with CKD-MBD, including FGF-23 and sclerostin, a known inhibitor of the Wnt signaling pathway. The molecular mechanisms that promote bone disease during the progression of CKD are incompletely understood. In this study, we performed a cross-sectional analysis of 87 pediatric patients with pre-dialysis CKD and post-dialysis (CKD 5D). We assessed the associations between serum and bone sclerostin levels and biomarkers of bone turnover and bone histomorphometry. We report that serum sclerostin levels were elevated in both early and late CKD. Higher circulating and bone sclerostin levels were associated with histomorphometric parameters of bone turnover and mineralization. Immunofluorescence analyses of bone biopsies evaluated osteocyte staining of antibodies towards the canonical Wnt target, ß-catenin, in the phosphorylated (inhibited) or unphosphorylated (active) forms. Bone sclerostin was found to be colocalized with phosphorylated ß-catenin, which suggests that Wnt signaling was inhibited. In patients with low serum sclerostin levels, increased unphosphorylated "active" ß-catenin staining was observed in osteocytes. These data provide new mechanistic insight into the pathogenesis of CKD-MBD and suggest that sclerostin may offer a potential biomarker or therapeutic target in pediatric renal osteodystrophy.

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