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This study examined the association between healthcare access and quality of life (QOL) among senior citizens in Pampanga, Philippines. We conducted a cross-sectional study among 410 community-dwelling senior citizens aged 60 and above. Using validated scales, we assessed both healthcare access and QOL. Descriptive statistics were employed to characterize the senior citizens, and multiple linear regression was used to examine the association between healthcare access and QOL. Senior citizens, averaging 69 years old, were predominantly women, single/widowed, and with comorbidities. They reported high healthcare access (mean = 120.13) and moderate QOL (mean = 70.79). Environmental health scored highest in QOL domains, while social relationships scored lowest. Overall healthcare access was positively associated with overall QOL (B [unstandardized beta] = .22, 95% CI [confidence interval] 0.10, 0.33) and its domains. Significant associations with overall QOL were observed for accessibility (B = 1.95, 95% CI 0.98, 2.91) and affordability (B = -1.60, 95% CI -2.46, -0.74). Filipino senior citizens in Pampanga demonstrated high healthcare access and moderate QOL. The study highlights the importance of healthcare access in enhancing senior citizens' QOL, particularly regarding accessibility and affordability. Further research is needed to explore the nuanced relationships between healthcare access subscales and specific QOL domains.
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Therapeutics enhancing apolipoprotein (APOE) positive function are a priority, because APOE4 is the major genetic risk factor for Alzheimer's disease (AD). The function of APOE, the key constituent of lipoprotein particles that transport cholesterol and lipids in the brain, is dependent on lipidation by ABCA1, a cell-membrane cholesterol transporter. ABCA1 transcription is regulated by liver X receptors (LXR): agonists have been shown to increase ABCA1, often accompanied by unwanted lipogenesis and elevated triglycerides (TG). Therefore, nonlipogenic ABCA1-inducers (NLAI) are needed. Two rounds of optimization of an HTS hit, derived from a phenotypic screen, gave lead compound 39 that was validated and tested in E3/4FAD mice that express human APOE3/4 and five mutant APP and PSEN1 human transgenes. Treatment with 39 increased ABCA1 expression, enhanced APOE lipidation, and reversed multiple AD phenotypes, without increasing TG. This NLAI/LXR-agonist study is the first in a human APOE-expressing model with hallmark amyloid-ß pathology.
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Transportador 1 de Cassete de Ligação de ATP , Doença de Alzheimer , Apolipoproteína E3 , Apolipoproteína E4 , Modelos Animais de Doenças , Camundongos Transgênicos , Animais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Humanos , Camundongos , Apolipoproteína E4/metabolismo , Apolipoproteína E4/genética , Apolipoproteína E3/genética , Apolipoproteína E3/metabolismo , Receptores X do Fígado/agonistas , Receptores X do Fígado/metabolismo , Presenilina-1/genética , Presenilina-1/metabolismoRESUMO
Some transgender youth are treated with gonadotropin-releasing hormone agonists (GnRHa) followed by testosterone or estradiol, which may impact bone mineral density (BMD). This cross-sectional study of transgender youth (n = 56, aged 10.4-19.8 years, 53% assigned female at birth [AFAB]) utilized total body dual-energy x-ray absorptiometry to evaluate BMD Z-scores, and associations between GnRHa duration, body mass index (BMI), and BMD. Participants on GnRHa alone (n = 19, 14 assigned male at birth [AMAB], 5 AFAB) at the time of the study visit were 13.8 [12.8, 15.3] (median [IQR]) years old, had been on GnRHa for 10 [5.5, 19.5] months, and began GnRHa at age 12 [10.4, 12.6] years. Total body BMD Z-score for individuals on GnRHa monotherapy was -0.10 [-0.8, 0.4] (AFAB, female norms) and -0.65 [-1.4, 0.22] (AMAB, male norms). AFAB participants (n = 21) on testosterone were age 16.7 [15.9, 17.8] years, had been on testosterone for 11 [7.3, 14.5] months, and started testosterone at age 16 [14.8, 16.8] years; total body BMD Z-score -0.2 [-0.5, 0] (male norms) and 0.4 [-0.2, 0.7] (female norms). AMAB participants (n = 16) were age 16.2 [15.1, 17.4] years, had been on estradiol for 11 [5.6, 13.7] months, and started estradiol at age 16 [14.4, 16.7] years; total body BMD Z-score -0.4 [-1.1, 0.3] (male norms) and -0.2 [-0.7, 0.6] (female norms). BMD Z-score was negatively correlated with GnRHa duration (male norms: r = -0.5, P = .005; female norms: r = -0.4, P = .029) and positively correlated with BMI (male norms: r = 0.4, P = .003; female norms: r = 0.4, P = .004). In this cross-sectional cohort, total body BMD Z-scores were slightly below average, but lowest in the AMAB group on GnRHa monotherapy.
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Doppler shift compensation (DSC) is a unique feature observed in certain species of echolocating bats and is hypothesized to be an adaptation to detecting fluttering insects. However, current research on DSC has primarily focused on bats that are not engaged in foraging activities. In this study, we investigated the DSC performance of Pratt's roundleaf bat, Hipposideros pratti, which was trained to pursue insects in various motion states within a laboratory setting. Our study yielded three main results. First, H. pratti demonstrated highly precise DSC during insect pursuit, aligning with previous findings of other flutter-detecting foragers during orientation or landing tasks. Second, we found that the motion state of the insect prey had little effect on the DSC performance of H. pratti. Third, we observed variations in the DSC performance of H. pratti throughout the course of insect pursuit. The bats exhibited the highest DSC performance during the phase of maximum flight speed but decreased performance during the phase of insect capture. These findings of high precision overall and the time-dependent performance of DSC during insect pursuit support the hypothesis that DSC is an adaptation to detecting fluttering insects.
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Quirópteros , Ecolocação , Animais , Efeito Doppler , Insetos , Comportamento PredatórioRESUMO
Pathogenic variants in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report a pooled analysis of clinical and laboratory records of 304 individuals from 145 kindreds, including 20 previously unreported HHRH kindreds, in which two novel SLC34A3 pathogenic variants were identified. Compound heterozygous/homozygous carriers show above 90% penetrance for kidney and bone phenotypes. The biochemical phenotype for heterozygous carriers is intermediate with decreased serum phosphate, tubular reabsorption of phosphate (TRP (%)), fibroblast growth factor 23, and intact parathyroid hormone, but increased serum 1,25-dihydroxy vitamin D, and urine calcium excretion causing idiopathic hypercalciuria in 38%, with bone phenotypes still observed in 23% of patients. Oral phosphate supplementation is the current standard of care, which typically normalizes serum phosphate. However, although in more than half of individuals this therapy achieves correction of hypophosphatemia it fails to resolve the other outcomes. The American College of Medical Genetics and Genomics score correlated with functional analysis of frequent SLC34A3 pathogenic variants in vitro and baseline disease severity. The number of mutant alleles and baseline TRP (%) were identified as predictors for kidney and bone phenotypes, baseline TRP (%) furthermore predicted response to therapy. Certain SLC34A3/NPT2c pathogenic variants can be identified with partial responses to therapy, whereas with some overlap, others present only with kidney phenotypes and a third group present only with bone phenotypes. Thus, our report highlights important novel clinical aspects of HHRH and heterozygous carriers, raises awareness to this rare group of disorders and can be a foundation for future studies urgently needed to guide therapy of HHRH.
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Raquitismo Hipofosfatêmico Familiar , Hipofosfatemia , Humanos , Raquitismo Hipofosfatêmico Familiar/complicações , Raquitismo Hipofosfatêmico Familiar/diagnóstico , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Hipercalciúria/diagnóstico , Hipercalciúria/tratamento farmacológico , Hipercalciúria/genética , Rim/metabolismo , Fosfatos , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIc/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIc/metabolismoRESUMO
OBJECTIVES: Pediatric patients diagnosed with inflammatory bowel disease (IBD) are at risk of suboptimal peak bone mass attainment. This study aimed to understand rates of bone health screening adherence, describe factors associated with dual-energy X-ray absorptiometry (DXA) acquisition, and identify factors associated with abnormal DXA. METHODS: We performed a retrospective cohort study of pediatric IBD patients over a 10-year time frame. We included IBD patients (2-20 years of age) enrolled in ImproveCareNow and excluded patients with primary metabolic bone disease. Time-to-event methods and multivariable logistic regression were employed to identify factors associated with DXA acquisition and abnormal DXA. RESULTS: In 676 patients, 464 (68.63%) pediatric patients with IBD had a risk factor for low bone mineral density (BMD); 137 (29.53%) underwent an initial DXA scan. Quiescent disease was significantly associated with a reduced likelihood of DXA (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.24-0.97), while weight z-score <-2 was significantly associated with DXA performance (HR: 2.07; 95% CI: 1.08-3.98). Abnormal DXA results (BMD z-score ≤-1) occurred in 59 (35.54%) individuals. After adjusting for visit diagnosis, delayed puberty, severe disease course, 6 months or greater of steroid exposure, and history of fracture, BMI z-score <-1 (odds ratio: 5.45; 95% CI: 2.41-12.33) was associated with abnormal DXA. CONCLUSIONS: DXA screening occurred in less than one-third of eligible pediatric IBD patients. Compliance was more common in patients with a weight z-score <-2 and less common in those with quiescent disease. BMI strongly predicted abnormal DXA results when adjusting for risk factors for abnormal BMD.
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Doenças Ósseas Metabólicas , Doenças Inflamatórias Intestinais , Humanos , Criança , Absorciometria de Fóton/efeitos adversos , Absorciometria de Fóton/métodos , Densidade Óssea , Estudos Retrospectivos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/diagnósticoRESUMO
Depletion of nicotinamide adenine dinucleotide (NAD+) is associated with aging and disease, spurring the study of dietary supplements to replenish NAD+. The catabolism of NAD+ to nicotinamide (NAM) requires the salvage of NAM to replenish cellular NAD+, which relies on the rate-limiting enzyme nicotinamide phosphoribosyltransferase (NAMPT). Pharmacological activation of NAMPT provides an alternative to dietary supplements. Screening for activators of NAMPT identified small molecule NAMPT positive allosteric modulators (N-PAMs). N-PAMs bind to the rear channel of NAMPT increasing enzyme activity and alleviating feedback inhibition by NAM and NAD+. Synthesis of over 70 N-PAMs provided an excellent correlation between rear channel binding affinity and potency for enzyme activation, confirming the mechanism of allosteric activation via binding to the rear channel. The mechanism accounts for higher binding affinity leading to loss of efficacy. Enzyme activation translated directly to elevation of NAD+ measured in cells. Optimization led to an orally bioavailable N-PAM.
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NAD , Nicotinamida Fosforribosiltransferase , Nicotinamida Fosforribosiltransferase/química , Nicotinamida Fosforribosiltransferase/metabolismo , NAD/metabolismo , Niacinamida/farmacologia , Linhagem Celular Tumoral , Citocinas/metabolismo , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: The objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily. METHODS: An updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: For adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies.
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Fraturas Ósseas , Osteoporose , Reumatologia , Adulto , Criança , Humanos , Estados Unidos , Glucocorticoides/efeitos adversos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Densidade ÓsseaRESUMO
Background: TransCon CNP (navepegritide) is an investigational prodrug of C-type natriuretic peptide (CNP) designed to allow for continuous CNP exposure with once-weekly dosing. This 52-week phase 2 (ACcomplisH) trial assessed the safety and efficacy of TransCon CNP in children with achondroplasia. Methods: ACcomplisH is a global, randomised, double-blind, placebo-controlled, dose-escalation trial. Study participants were recruited between June 10, 2020, and September 24, 2021. Eligible participants were prepubertal, aged 2-10 years, with genetically confirmed achondroplasia, and randomised 3:1 to once-weekly subcutaneous injections of TransCon CNP (6, 20, 50, or 100 µg CNP/kg/week) or placebo for 52 weeks. Primary objectives were safety and annualised growth velocity (AGV). ACcomplisH is registered with ClinicalTrials.gov (NCT04085523) and Eudra (CT 2019-002754-22). Findings: Forty-two participants received TransCon CNP at doses of 6 µg (n = 10; 7 female), 20 µg (n = 11; 3 female), 50 µg (n = 10; 3 female), or 100 µg (n = 11; 6 female) CNP/kg/week, with 15 receiving placebo (5 female). Treatment-emergent adverse events (TEAEs) were mild or moderate with no grade 3/4 events reported. There were 2 serious TEAEs that were assessed as not related to TransCon CNP. Eleven injection site reactions occurred in 8 participants receiving TransCon CNP and no symptomatic hypotension occurred. TransCon CNP demonstrated a dose-dependent improvement in AGV. At 52 weeks, TransCon CNP 100 µg CNP/kg/week significantly improved AGV vs placebo (least squares mean [95% CI] 5.42 [4.74-6.11] vs 4.35 [3.75-4.94] cm/year; p = 0.0218), and improved achondroplasia-specific height SDS from baseline (least squares mean [95% CI] 0.22 [0.02-0·41] vs -0·08 [-0.25 to 0.10]; p = 0.0283). All participants completed the randomised period and continued in the ongoing open-label extension period receiving TransCon CNP 100 µg CNP/kg/week. Interpretation: This phase 2 trial suggests that TransCon CNP is effective, safe, with low injection site reaction frequency, and may provide a novel, once-weekly treatment option for children with achondroplasia. These results support TransCon CNP at 100 µg CNP/kg/week in the ongoing pivotal trial. Funding: Ascendis Pharma, A/S.
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Predator-prey interactions are important but difficult to study in the field. Therefore, laboratory studies are often used to examine the outcomes of predator-prey interactions. Previous laboratory studies have shown that moth hearing and ultrasound production can help prey avoid being eaten by bats. We report here that laboratory behavioural outcomes may not accurately reflect the outcomes of field bat-moth interactions. We tested the success rates of two bat species capturing moths with distinct anti-bat tactics using behavioural experiments. We compared the results with the dietary composition of field bats using next-generation DNA sequencing. Rhinolophus episcopus and Rhinolophus osgoodi had a lower rate of capture success when hunting for moths that produce anti-bat clicks than for silent eared moths and earless moths. Unexpectedly, the success rates of the bats capturing silent eared moths and earless moths did not differ significantly from each other. However, the field bats had a higher proportion of silent eared moths than that of earless moths and that of clicking moths in their diets. The difference between the proportions of silent eared moths and earless moths in the bat diets can be explained by the difference between their abundance in bat foraging habitats. These findings suggest that moth defensive tactics, bat countertactics and moth availability collectively shape the diets of insectivorous bats. This study illustrates the importance of using a combination of behavioural experiments and molecular genetic techniques to reveal the complex interactions between predators and prey in nature.
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Quirópteros , Ecolocação , Mariposas , Animais , Mariposas/genética , Quirópteros/genética , Comportamento Predatório , DietaRESUMO
OBJECTIVE: The objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily. METHODS: An updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: For adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies.
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Osteoporose , Reumatologia , Adulto , Criança , Humanos , Estados Unidos , Glucocorticoides/efeitos adversos , Osteoporose/induzido quimicamente , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Densidade ÓsseaRESUMO
Hypopharyngeal cancer (HPC) has one of the most unfavorable prognoses among head and neck squamous cell carcinomas. Immunotherapy in combination with chemotherapy, the same as conventional induction chemotherapy, has emerged as a vital part of the induction therapy protocol for HPC. Meanwhile, the incidence of immune-related adverse events is increasing. In this light, we present the first reported case of immune-associated encephalitis in a patient with hypopharyngeal cancer treated with Camrelizumab (a PD-1 inhibitor). After receiving immunotherapy combined with chemotherapy as induction therapy, along with concurrent chemoradiotherapy, the patient presented with symptoms of fatigue, tremors, drowsiness, and an abnormal signal in the right temporal lobe as shown on a brain magnetic resonance imaging (MRI). Despite the minor elevation in protein and IgG index observed in the lumbar puncture, there is no evidence of abnormal autoantibodies or evidence of pathogenic infection. Following a thorough multidisciplinary consultation, the patient is suspected to be afflicted with immune-related autoimmune encephalitis. Intravenous methylprednisolone was prescribed as an empirical treatment at an initial dosage of 120 mg/day for 3 days, followed by steroid tapering. Finally, the patient experienced complete neurologic and radiographic (brain MRI) recovery. This case serves as a critical reminder that encephalitis is a potential diagnosis that should never be overlooked in patients undergoing immunotherapy who present with abnormal signs of the brain. The timely diagnosis and initiation of immunosuppressive therapy are key components of treating ICI-associated encephalitis.
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Encefalite , Neoplasias Hipofaríngeas , Humanos , Nivolumabe , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Hipofaríngeas/tratamento farmacológico , Hipofaringe/patologia , Encefalite/induzido quimicamente , Encefalite/patologiaRESUMO
Multicentric carpotarsal osteolysis (MCTO) is a rare skeletal dysplasia characterized by osteolysis of the carpal and tarsal bones. Antiresorptive agents have proven ineffective and the pathogenesis of MCTO remains poorly understood. We report a young child with a novel variant in MAFB who demonstrated clinical improvement of joint symptoms following anti-rheumatic therapies. Also, radiographs from a young age suggest that dysfunctional bone formation may play a role in the skeletal phenotype of MCTO.
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BACKGROUND: Peroxisome proliferator activated receptors (PPARs) are a nuclear hormone receptors superfamily that is closely related to fatty acid (FA) metabolism and tumor progression. Solute carrier family 27 member 2 (SLC27A2) is important for FA transportation and metabolism and is related to cancer progression. This study aims to explore the mechanisms of how PPARs and SLC27A2 regulate FA metabolism in colorectal cancer (CRC) and find new strategies for CRC treatment. METHODS: Biological information analysis was applied to detect the expression and the correlation of PPARs and SLC27A2 in CRC. The protein-protein interaction (PPI) interaction networks were explored by using the STRING database. Uptake experiments and immunofluorescence staining were used to analyse the function and number of peroxisomes and colocalization of FA with peroxisomes, respectively. Western blotting and qRTâPCR were performed to explore the mechanisms. RESULTS: SLC27A2 was overexpressed in CRC. PPARs had different expression levels, and PPARG was significantly highly expressed in CRC. SLC27A2 was correlated with PPARs in CRC. Both SLC27A2 and PPARs were closely related to fatty acid oxidation (FAO)ârelated genes. SLC27A2 affected the activity of ATP Binding Cassette Subfamily D Member 3 (ABCD3), also named PMP70, the most abundant peroxisomal membrane protein. We found that the ratios of p-Erk/Erk and p-GSK3ß/GSK3ß were elevated through nongenic crosstalk regulation of the PPARs pathway. CONCLUSIONS: SLC27A2 mediates FA uptake and beta-oxidation through nongenic crosstalk regulation of the PPARs pathway in CRC. Targeting SLC27A2/FATP2 or PPARs may provide new insights for antitumour strategies.
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Neoplasias Colorretais , Receptores Ativados por Proliferador de Peroxissomo , Humanos , Ácidos Graxos/metabolismo , Glicogênio Sintase Quinase 3 beta , Receptores Citoplasmáticos e Nucleares , Coenzima A Ligases/metabolismoRESUMO
BACKGROUND: Sufentanil combined with parecoxib sodium is a commonly used postoperative medication for cancer patients. However, the effects of this combination therapy on human epidermal growth factor receptor-2 (HER2)-positive breast cancer cells have still remained elusive. This study aimed to investigate the effects and potential mechanisms of sufentanil combined with parecoxib sodium on HER2-positive breast cancer cells. METHODS: The cell counting kit-8 (CCK-8), colony formation, flow cytometry, scratch, transwell invasion, and angiogenesis assays were used to assess the proliferation, cell cycling, migration, invasion, and angiogenesis of HER2-positive breast cancer BT474 cells. Western blot assay was employed for detecting the expression levels of proteins involved in the cell cycle, migration, invasion, angiogenesis, and epithelial-mesenchymal transition (EMT). The in vivo effects of tumor growth and metastasis were examined by establishing an orthotopic transplantation mouse model of HER2-positive breast cancer (MMTV-PyMT). RESULTS: Functional assays indicated that sufentanil combined with parecoxib sodium induced blockade of HER2-positive breast cancer BT474 cells in the G1 phase of the cell cycle and inhibited cell proliferation, migration, angiogenesis, and invasion in vitro. Western blot assay revealed that sufentanil combined with parecoxib sodium downregulated the expression levels of cyclin D1, matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), vascular endothelial growth factor A (VEGFA), and EMT-related proteins (N-cadherin, Vimentin, and Snail), while up-regulated the expression level of E-cadherin in BT474 cells. In addition, it was found that sufentanil combined with parecoxib sodium inhibited tumor growth and metastasis in the orthotopic transplantation mouse model of HER2-positive breast cancer. CONCLUSION: Sufentanil combined with parecoxib sodium inhibited HER2-positive breast cancer progression, including cell proliferation, cell cycle, migration, invasion, and angiogenesis, and regulated EMT.
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Neoplasias da Mama , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Sufentanil/farmacologia , Fator A de Crescimento do Endotélio VascularRESUMO
PURPOSE OF REVIEW: Multicentric carpotarsal osteolysis (MCTO) is an ultra-rare disorder characterized by osteolysis of the carpal and tarsal bones, subtle craniofacial deformities, and nephropathy. The molecular pathways underlying the pathophysiology are not well understood. RECENT FINDINGS: MCTO is caused by heterozygous mutations in MAFB, which encodes the widely expressed transcription factor MafB. All MAFB mutations in patients with MCTO result in replacement of amino acids that cluster in a phosphorylation region of the MafB transactivation domain and account for a presumed gain-of-function for the variant protein. Since 2012, fewer than 60 patients with MCTO have been described with 20 missense mutations in MAFB. The clinical presentations are variable, and a genotype-phenotype correlation is lacking. Osteolysis, via excessive osteoclast activity, has been regarded as the primary mechanism, although anti-resorptive agents demonstrate little therapeutic benefit. This paper appraises current perspectives of MafB protein action, inflammation, and dysfunctional bone formation on the pathogenesis of the skeletal phenotype in MCTO. More research is needed to understand the pathogenesis of MCTO to develop rational therapies.
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Ossos do Carpo , Osteólise , Humanos , Osteólise/genética , Mutação , Mutação de Sentido Incorreto , Ossos do Carpo/patologia , FenótipoRESUMO
BACKGROUND: Children with medical complexity are at increased risk of low bone mineral density (BMD) and complications after spinal fusion compared with idiopathic scoliosis patients. Our aim was to compare treatments and outcomes of children with medical complexity undergoing spinal fusion in those who had dual-energy x-ray absorptiometry (DXA) scans versus those who did not in an effort to standardize the workup of these patients before undergoing spinal surgery. METHODS: We conducted a retrospective review of patients with low BMD who underwent spinal fusion at a tertiary care pediatric hospital between 2004 and 2016. We consulted with a pediatric endocrinologist to create standard definitions for low BMD to classify each subject. Regardless of DXA status, all patients were given a clinical diagnosis of osteoporosis [at least 2 long bone or 1 vertebral pathologic fracture(s)], osteopenia (stated on radiograph or by the physician), or clinically low bone density belonging to neither category. The last classification was used for patients whose clinicians had documented low bone density not meeting the criteria for osteoporosis or osteopenia. Fifty-nine patients met the criteria, and 314 were excluded for insufficient follow-up and/or not meeting a diagnosis definition. BMD Z -scores compare bone density ascertained by DXA to an age-matched and sex-matched average. Patients who had a DXA scan were also given a DXA diagnosis of low bone density (≤-2 SD), slightly low bone density (-1.0 to -1.9 SD), or neither (>-1.0 SD) based on the lowest BMD Z -score recorded. RESULTS: Fifty-nine patients were analyzed. Fifty-four percent had at least 1 DXA scan preoperatively. Eighty-one percent of DXA patients received some form of treatment compared with 52% of non-DXA patients ( P =0.03). CONCLUSIONS: Patients referred for DXA scans were more likely to be treated for low BMD, although there is no standardized system in place to determine which patients should get scans. Our research highlights the need to implement clinical protocols to optimize bone health preoperatively. LEVEL OF EVIDENCE: Level II-retrospective prognostic study.
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Doenças Ósseas Metabólicas , Osteoporose , Fraturas da Coluna Vertebral , Fusão Vertebral , Absorciometria de Fóton/efeitos adversos , Absorciometria de Fóton/métodos , Densidade Óssea , Doenças Ósseas Metabólicas/diagnóstico por imagem , Criança , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Osteoporose/diagnóstico por imagem , Estudos Retrospectivos , Fraturas da Coluna Vertebral/complicações , Fusão Vertebral/efeitos adversosRESUMO
The Simao Basin is one of the most important Mesozoic salt basins in China, and the salt rocks generally contain mud-clast conglomerates. The characteristics of mud-clast conglomerates can provide effective information indicating the evolution process of the salt deposits. A combined analysis of trace elements and clay minerals was performed to characterize the genetic model of mud-clast conglomerates in the salt rocks. The results show that the sedimentary materials are felsic rocks from the Upper Crust. Ternary plot diagrams show that the tectonic settings are between the continental margin and the continental island arc. The clay minerals in the samples mainly contain illite and illite-smectite mixed layers. A dry and hot climate prevailed during the deposition of the Mengyejing Formation, and the warm-humid climate that also occurred is interspersed in some periods. Evaporation makes the water bodies shallower, and the concentrated brine starts to precipitate salt under the arid and hot climate conditions. Redox proxies indicate that most of the samples were deposited in relatively oxic conditions. The Sr/Ba ratios (average of 0.5) and paleosalinity (average of â¼35) during the depositional period indicate an increase in terrigenous freshwater input and carry of clasts into the evaporation basin. Furthermore, the freshwater supply enhances the hydrodynamics; as a result, the detritus that deposited in the early stage is broken into mud-clast conglomerates and co-deposited with the salt rocks. The results provide a geochemical basis for further study of mud-clast conglomerates in the Simao Basin and supply recommendations for the origin of salt deposits in similar basins around the world.