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INTRODUCTION: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications. Recently, PPI use has been linked to the development of chronic kidney disease (CKD) and cardiovascular events. Our study aimed to investigate the relationship between PPI use and the incidence of chronic kidney disease using a systematic review and meta-analysis. METHODS: We performed a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until March 2024 for relevant studies. We compared outcomes between patients using PPIs, those not using PPIs, and those using histamine-2 receptor antagonists (H2RAs). Endpoints were pooled using the DerSimonian-and-Laird random-effects model as the hazard ratio (HR) with 95% confidence intervals (CIs). RESULTS: Our analysis included twelve studies with a total of 700,125 participants (286,488 on PPIs, 373,848 not on PPIs, and 39,789 on H2RAs), with follow-up periods ranging from three months to 14 years. The current meta-analysis revealed that PPI use is associated with a statistically significant increased risk of incident CKD (HR: 1.26, 95% CI: 1.16-1.38, p < 0.001) compared with non-users. Moreover, the risk of incident CKD is significantly higher in patients with PPI use compared to H2RA use (HR: 1.34, 95% CI: 1.13-1.59, p < 0.001). The results remained unchanged in terms of magnitude and direction after a leave-one-out analysis for both outcomes. CONCLUSIONS: Our multifaceted analysis showed that PPI use was associated with a higher incidence of CKD when compared to non-PPI use and H2RA use, respectively. These findings advocate for heightened vigilance and judicious use of long-term PPIs. Further large prospective longitudinal studies are warranted to validate these observations.
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PURPOSE: Colorectal cancer screening is recommended starting at age 45, but there has been little research on strategies to promote screening in patients younger than 50. METHODS: An outreach program quasi-randomly assigned patients aged 45-50 without recent fecal immunochemical test (FIT), colonoscopy or contraindications to screening to two intervention arms: electronic outreach with email and text (electronic outreach only) versus electronic outreach plus mailed outreach with FIT, an instructional letter and a prepaid return envelope (mailed + electronic outreach). In response to known disparities in screening uptake, all Black patients were assigned to receive mailed + electronic outreach. RESULTS: Among patients quasi-randomly assigned to an intervention (non-Black patients), the 180-day FIT completion rate was 18.8% in the electronic outreach only group (n = 1,318) and 25.0% in the mailed + electronic outreach group (n = 1,364) (difference 6.2% [95% CI 3.0, 9.4]). FIT completion was 16.6% among Black patients (n = 469), 8.4% (95% CI 4.1, 12.6) lower than among non-Black patients also assigned to mailed + electronic outreach. CONCLUSION: Among patients aged 45-50, mailed + electronic outreach had a greater effect on FIT completion than electronic outreach alone. Crossover between intervention groups likely lead to an underestimation of the effect of mailed outreach.
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This work reports in situ (active) electrochemical control over the coupling strength between semiconducting nanoplatelets and a plasmonic cavity. We found that by applying a reductive bias to an Al nanoparticle lattice working electrode the number of CdSe nanoplatelet emitters that can couple to the cavity is decreased. Strong coupling can be reversibly recovered by discharging the lattice at oxidative potentials relative to the conduction band edge reduction potential of the emitters. By correlating the number of electrons added or removed with the measured coupling strength, we identified that loss and recovery of strong coupling are likely hindered by side processes that trap and/or inhibit electrons from populating the nanoplatelet conduction band. These findings demonstrate tunable, external control of strong coupling and offer prospects to tune selectivity in chemical reactions.
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A 33-year-old female was admitted for community-acquired pneumonia. On presentation, she was tachypneic and tachycardic and leukocytosis at 28,900/µL. Chest imaging showed dense consolidation on the right upper lobe. Due to refractory worsening respiratory failure, she was intubated with mechanical ventilation. Initial bronchoscopy with culture data was negative. Extracorporeal membrane oxygenation was pursued on the fourth day. Repeat bronchoscopy revealed targetoid ulcerative lesions with erythema in the right middle, lower lobes and left lower lobe. We describe a case of herpes simplex virus pneumonia in an immunocompetent patient that occurred in the setting of acute bacterial infection.
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Nanotechnology and nanoparticles have gained massive attention in the scientific community in recent years due to their valuable properties. Among various AgNPs synthesis methods, microbial approaches offer distinct advantages in terms of cost-effectiveness, biocompatibility, and eco-friendliness. In the present research work, investigators have synthesized three different types of silver nanoparticles (AgNPs), namely AgNPs-K, AgNPs-M, and AgNPs-E, by using Klebsiella pneumoniae (MBC34), Micrococcus luteus (MBC23), and Enterobacter aerogenes (MBX6), respectively. The morphological, chemical, and elemental features of the synthesized AgNPs were analyzed by using UV-Vis spectroscopy (UV-Vis), Fourier transform-infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscope (FESEM) and energy-dispersive spectroscopy (EDX). UV-Vis absorbance peaks were obtained at 475, 428, and 503 nm for AgNPs-K, AgNPs-M, and AgNPs-E, respectively. The XRD analysis confirmed the crystalline nature of the synthesized AgNPs, having peaks at 26.2°, 32.1°, and 47.2°. At the same time, the FTIR showed bands at 599, 963, 1,693, 2,299, 2,891, and 3,780 cm-1 for all the types of AgNPs indicating the presence of bacterial biomolecules with the developed AgNPs. The size and morphology of the AgNPs varied from 10 nm to several microns and exhibited spherical to porous sheets-like structures. The percentage of Ag varied from 37.8% (wt.%) to 61.6%, i.e., highest in AgNPs-K and lowest in AgNPs-M. Furthermore, the synthesized AgNPs exhibited potential for environmental remediation, with AgNPs-M exhibiting the highest removal efficiency (19.24% at 120 min) for methyl orange dye in simulated wastewater. Further, all three types of AgNPs were evaluated for the removal of methyl orange dye from the simulated wastewater, where the highest dye removal percentage was 19.24% at 120 min by AgNPs-M. Antibacterial potential of the synthesized AgNPs assessment against both Gram-positive (GPB) Bacillus subtilis (MBC23), B. cereus (MBC24), and Gram-negative bacteria Enterococcus faecalis (MBP13) revealed promising results, with AgNPs-M, exhibiting the largest zone of inhibition (12 mm) against GPB B. megaterium. Such investigation exhibits the potential of the bacteria for the synthesis of AgNPs with diverse morphology and potential applications in environmental remediation and antibacterial therapy-based synthesis of AgNPs.
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Compostos Azo , Nanopartículas Metálicas , Micrococcus luteus , Prata , Prata/química , Prata/farmacologia , Prata/metabolismo , Nanopartículas Metálicas/química , Compostos Azo/química , Compostos Azo/farmacologia , Compostos Azo/metabolismo , Micrococcus luteus/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/metabolismo , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/química , Enterobacter aerogenes/efeitos dos fármacos , Enterobacter aerogenes/metabolismo , Difração de Raios X , Poluentes Químicos da Água/metabolismo , Corantes/química , Corantes/farmacologiaRESUMO
PURPOSE: We wished to evaluate if an open-source artificial intelligence (AI) algorithm ( https://www.childfx.com ) could improve performance of (1) subspecialized musculoskeletal radiologists, (2) radiology residents, and (3) pediatric residents in detecting pediatric and young adult upper extremity fractures. MATERIALS AND METHODS: A set of evaluation radiographs drawn from throughout the upper extremity (elbow, hand/finger, humerus/shoulder/clavicle, wrist/forearm, and clavicle) from 240 unique patients at a single hospital was constructed (mean age 11.3 years, range 0-22 years, 37.9% female). Two fellowship-trained musculoskeletal radiologists, three radiology residents, and two pediatric residents were recruited as readers. Each reader interpreted each case initially without and then subsequently 3-4 weeks later with AI assistance and recorded if/where fracture was present. RESULTS: Access to AI significantly improved area under the receiver operator curve (AUC) of radiology residents (0.768 [0.730-0.806] without AI to 0.876 [0.845-0.908] with AI, P < 0.001) and pediatric residents (0.706 [0.659-0.753] without AI to 0.844 [0.805-0.883] with AI, P < 0.001) in identifying fracture, respectively. There was no evidence of improvement for subspecialized musculoskeletal radiology attendings in identifying fracture (AUC 0.867 [0.832-0.902] to 0.890 [0.856-0.924], P = 0.093). There was no evidence of difference between overall resident AUC with AI and subspecialist AUC without AI (resident with AI 0.863, attending without AI AUC 0.867, P = 0.856). Overall physician radiograph interpretation time was significantly lower with AI (38.9 s with AI vs. 52.1 s without AI, P = 0.030). CONCLUSION: An openly accessible AI model significantly improved radiology and pediatric resident accuracy in detecting pediatric upper extremity fractures.
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Semiconductor nanocrystals (NCs) can function as efficient gain materials with chemical versatility because of their surface ligands. Because the properties of NCs in solution are sensitive to ligand-environment interactions, local chemical changes can result in changes in the optical response. However, amplification of the optical response is technically challenging because of colloidal instability at NC concentrations needed for sufficient gain to overcome losses. This paper demonstrates liquid lasing from plasmonic lattice cavities integrated with ligand-engineered CdZnS/ZnS NCs dispersed in toluene and water. By taking advantage of calcium ion-induced aggregation of NCs in aqueous solutions, we show how lasing threshold can be used as a transduction signal for ion detection. Our work highlights how NC solutions and plasmonic lattices with open cavity architectures can serve as a biosensing platform for lab-on-chip devices.
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INTRODUCTION: We examined the utility of the International Classification of Disease, Tenth Revision (ICD-10) code, R19.5, for a positive or abnormal fecal immunochemical test (FIT) and its association with colonoscopy completion. METHODS: We identified all patients in a safety-net health system who underwent FITs from January 1, 2020, to August 31, 2021, and extracted the FIT date, FIT result, and ICD-10 code (R19.5) and colonoscopy procedures for each patient. RESULTS: FIT-positive patients who had an R19.5 designation within 90 days (n = 383) were significantly more likely than all other FIT-positive patients (n = 273) to complete a colonoscopy within 6 months (40.9% vs 16.8%, P <0.001). DISCUSSION: We found that less than two-thirds of patients had an ICD-10 code designated in their chart within 30 days of an abnormal FIT. When coding occurred in a timely manner, patients were more likely to complete their colonoscopy within 6 months.
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Colonoscopia , Classificação Internacional de Doenças , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Sangue Oculto , Neoplasias Colorretais/diagnóstico , Fezes/química , Detecção Precoce de Câncer/métodos , Codificação Clínica , Estudos RetrospectivosRESUMO
STUDY OBJECTIVES: To examine the associations between sleep duration, continuity, timing, and mortality using actigraphy among adults. METHODS: Data were from a cohort of 88 282 adults (40-69 years) in UK Biobank that wore a wrist-worn triaxial accelerometer for 7 days. Actigraphy data were processed to generate estimates of sleep duration and other sleep characteristics including wake after sleep onset (WASO), number of 5-minute awakenings, and midpoint for sleep onset/wake-up and the least active 5 hours (L5). Data were linked to mortality outcomes with follow-up to October 31, 2021. We implemented Cox models (hazard ratio, confidence intervals [HR, 95% CI]) to quantify sleep associations with mortality. Models were adjusted for demographics, lifestyle factors, and medical conditions. RESULTS: Over an average of 6.8 years 2973 deaths occurred (1700 cancer, 586 CVD deaths). Overall sleep duration was significantly associated with risk for all-cause (pâ <â 0.01), cancer (pâ <â 0.01), and CVD (pâ =â 0.03) mortality. For example, when compared to sleep durations of 7.0 hrs/d, durations of 5 hrs/d were associated with a 29% higher risk for all-cause mortality (HR: 1.29 [1.09, 1.52]). WASO and number of awakenings were not associated with mortality. Individuals with L5 early or late midpoints (<2:30 orâ ≥â 3:30) had a ~20% higher risk for all-cause mortality, compared to those with intermediate L5 midpoints (3:00-3:29; pâ ≤â 0.01; e.g. HR ≥ 3:30: 1.19 [1.07, 1.32]). CONCLUSIONS: Shorter sleep duration and both early and late sleep timing were associated with a higher mortality risk. These findings reinforce the importance of public health efforts to promote healthy sleep patterns in adults.
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Doenças Cardiovasculares , Neoplasias , Adulto , Humanos , Actigrafia , Duração do Sono , Biobanco do Reino Unido , Bancos de Espécimes Biológicos , SonoRESUMO
Phytonanofabrication is one of the most promising areas that has drawn the attention of scientists worldwide due to its eco-friendly nature and biocompatibility. In the current investigation, we reported the phyto-assisted formation of iron oxide nanoparticles (IONPs) from a rare species of Acacia (Acacia jacquemontii). First, ethanolic extracts of the stem powder were analyzed by high-performance thin-layer chromatography (HPTLC) for the identification of phytochemicals in the stem sections of Acacia. Furthermore, IONPs were synthesized by a chemical co-precipitation method by using the stem extract. The phytonanofabricated iron oxide particles were investigated by UV-Vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and Energy-dispersive X-ray spectroscopy (EDS) for elemental analysis. HPTLC confirmed the presence of several phenols and terpenoids in the ethanolic extracts of the stem. UV-Vis spectroscopy exhibited an absorbance peak at 380 nm, indicating the formation of IONPs, while FTIR spectroscopy showed the typical bands for Fe-O in the range of 599-1,000 cm-1 in addition to several functional groups of organic molecules at 1,596 cm-1, 2,313 cm-1, and 3,573 cm-1. XRD exhibits the amorphous nature of IONPs with peaks at 30.7, 35.5, and 62.7 nm. The IONPs were spherical-shaped, whose size varies from 10 to 70 nm, as confirmed by FESEM. EDS exhibited the presence of Fe, O, C, and NaCl. Finally, the phytonanofabricated iron oxide particles were utilized for the removal of brilliant green (BG) and Congo red (CR) dye from the aqueous solution. The removal efficiency of BG dye was up to 54.28%, while that of Congo red dye was up to 36.72% in 120 min and 60 min, respectively. Furthermore, the effect of pH and contact time was also assessed on both the dyes, where CR exhibited maximum removal at acidic pH, i.e., 47.5%, while BG showed maximum removal at pH 10, i.e., 76.59%.
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X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence of dental abscesses and periodontal disease, likely driven by poorly formed structures of the dentoalveolar complex, including the alveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (Scl-Ab) treatment improves phosphate homeostasis, and increases long bone mass, strength, and mineralization in the Hyp mouse model of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male and female wild-type and Hyp littermates were injected with 25 mg·kg-1 of vehicle or Scl-Ab twice weekly beginning at 12 weeks of age and euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineral density in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active (nonphosphorylated) ß-catenin, dentin matrix protein 1 (DMP1) and osteopontin stained alveolar osteocytes. Scl-Ab had no effect on the mass and mineralization of dentin, enamel, acellular or cellular cementum. There was a nonsignificant trend toward increased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fiber structural parameters were not affected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in adult Hyp mice.
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Raquitismo Hipofosfatêmico Familiar , Dente , Camundongos , Masculino , Feminino , Animais , Raquitismo Hipofosfatêmico Familiar/metabolismo , Osso e Ossos/metabolismo , Dente/metabolismo , Ligamento Periodontal/metabolismoRESUMO
The population worldwide is getting older as a result of advances in public health, medicine, and technology. Older individuals are living longer with a higher prevalence of subclinical and clinical cardiovascular disease (CVD). In 2010, the American Heart Association introduced a list of key prevention targets, known as "Life's Simple 7" to increase CVD-free survival, longevity, and quality of life. In 2022, sleep health was added to expand the recommendations to "Life's Essential 8" (eat better, be more active, stop smoking, get adequate sleep, manage weight, manage cholesterol, manage blood pressure, and manage diabetes). These prevention targets are intended to apply regardless of chronologic age. During this same time, the understanding of aging biology and goals of care for older adults further enhanced the relevance of prevention across the range of functions. From a biological perspective, aging is a complex cellular process characterized by genomic instability, telomere attrition, loss of proteostasis, inflammation, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These aging hallmarks are triggered by and enhanced by traditional CVD risk factors leading to geriatric syndromes (eg, frailty, sarcopenia, functional limitation, and cognitive impairment) which complicate efforts toward prevention. Therefore, we review Life's Essential 8 through the lens of aging biology, geroscience, and geriatric precepts to guide clinicians taking care of older adults.
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We present the case of a 52-year-old male who arrived at the Emergency Department after several ground-level falls in the past month. He complained of urinary incontinence, mild confusion, headaches, and appetite loss in the past month as well. Brain computed tomography (CT) and magnetic resonance imaging (MRI) were performed, which showed enlarged ventricles with moderately prominent cortical atrophy and no acute abnormalities. It was decided to conduct a cisternogram study with serial scans. The study showed a type IIIa cerebrospinal fluid (CSF) flow pattern at 24 hours. At the 48- and 72-hour marks, the study displayed an absence of radiotracer activity within the ventricles, while all the activity was concentrated within the cerebral cortices. These findings successfully ruled out normal pressure hydrocephalus (NPH) due to the highly specific indication of normal CSF circulation pattern. The patient was treated with thiamine and advised to quit drinking, as well as return for follow-up in one month as an outpatient for a repeat brain CT.
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OBJECTIVE: This study evaluates the impact of offering a clinical decision-making and problem-solving course to students academically challenged in early required clinical and pharmaceutical calculation courses on improving their ability to identify and solve drug-related problems. METHODS: Faculty designed a course with a main objective for students with grades of C or lower in any of the 5 required first-year courses to gain plentiful practice with a systematic approach to identifying and solving drug therapy problems. Students' performance on course-embedded assessments mapped to problem-solver subdomain, a pre-Advanced Pharmacy Practice Experience (APPE) competency on the ability to identify drug-related problems, and performance on Pharmacy Curriculum Outcomes Assessment were compared to a control group of students from 2 previous cohorts who did not take the course but had a subpar academic performance. Pearson chi-square test and independent samples t test were utilized for categorical and continuous data, respectively. RESULTS: The clinical decision-making and problem-solving course significantly improved student performance on pre-APPE competency to identify drug-related problems (first-attempt pass rate of 96% vs 30% when compared to a historic cohort), but not on Pharmacy Curriculum Outcomes Assessment. Student performance on case-based questions mapped to problem-solver subdomain exceeded internally set standard by 13.72% points. CONCLUSION: Students demonstrated learning problem-solving and clinical decision-making, which improved their performance on course-embedded assessments and pre-APPE competency in identifying drug-related problems.
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Educação em Farmácia , Assistência Farmacêutica , Farmácia , Humanos , Currículo , EstudantesRESUMO
Background: Diabetes mellitus (DM) is a group of metabolic disorders that have an increased risk of macro and micro-vascular complications due to lipid dysfunction. The present drug treatments for the management of DM either have numerous side effects or do not have long-lasting therapeutic effects. So it is essential to find a newer class of drug for DM treatment. Method: Broad information has been researched regarding Tyrosine kinase Inhibitors (TKIs) and their mechanism of action. They are proven for the management of various kinds of cancers. TKIs produce anti-hyperglycemic effects by acting on multiple targets such as c-Abl, Platelet-Derived Growth Factor Receptor (PDGFR), Vascular Endothelial Growth Factor Receptor (VEGFR), Epidermal Growth Factor Receptor (EGFR), and c-Kit. Result: This family of drugs blocks numerous tyrosine kinases by acting as a partial agonist of PPAR-γ receptors and results in an anti-diabetic effect by improving insulin sensitivity and glucose disposal rate. Conclusion: Therefore, it is said that TKI drugs will be great potential for the treatment of Diabetes. This review summarizes the possible targets of TKIs and TKIs being a potential drug class in the management of Diabetes mellitus.
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A 33-year-old male with a past medical history of asthma presented to the Emergency room with a three-day history of right-sided chest pain, productive cough with dark brown sputum, and shortness of breath. He was found to have right lower lobe consolidation consistent with acute pneumonia, and areas of non-homogenous density within the consolidation, suspicious of necrotizing pneumonia. Computed tomography (CT) of the chest with IV contrast revealed a large, irregular thick-walled cavitary mass involving the right middle lobe with surrounding ground glass cavitation. An extensive workup was negative, including a transbronchial biopsy. The case explains how a causative organism was detected.
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The accumulation and aggregation of the microtubule-associated protein tau (tau) into intracellular neuronal tangles are a hallmark of a range of progressive neurodegenerative tauopathies, including Alzheimer's disease (AD), frontotemporal dementia, Pick's disease, and progressive supranuclear palsy. The aberrant phosphorylation of tau is associated with tau aggregates in AD. Members of the heat shock protein 70 kDa (Hsp70) family of chaperones bind directly to tau and modulate tau clearance and aggregation. Small molecules that inhibit the Hsp70 family of chaperones have been shown to reduce the accumulation of tau, including phosphorylated tau. Here, eight analogs of the rhodacyanine inhibitor, JG-98, were synthesized and evaluated. Like JG-98, many of the compounds inhibited ATPase activity of the cytosolic heat shock cognate 70 protein (Hsc70) and reduced total, aggregated, and phosphorylated tau accumulation in cultured cells. Three compounds, representing divergent clogP values, were evaluated for in vivo blood-brain barrier penetration and tau reduction in an ex vivo brain slice model. AL69, the compound with the lowest clogP and the lowest membrane retention in a parallel artificial membrane permeability assay (PAMPA), reduced phosphorylated tau accumulation. Our results suggest that benzothiazole substitutions of JG-98 that increase hydrophilicity may increase the efficacy of these Hsp70 inhibitors to reduce phosphorylated tau.
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Doença de Alzheimer , Tauopatias , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Benzotiazóis/farmacologia , Proteínas de Choque Térmico HSP70 , Chaperonas Moleculares , Proteínas tau/metabolismo , Tauopatias/metabolismoRESUMO
X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and poor mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence of dental abscesses, likely driven by poorly formed structures of the dentoalveolar complex, including the alveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (Scl-Ab) treatment improves phosphate homeostasis, and increases bone mass, strength and mineralization in the Hyp mouse model of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male and female wild-type and Hyp littermates were injected with 25 mg/kg of vehicle or Scl-Ab twice weekly beginning at 12 weeks of age and euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineral density in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active (non-phosphorylated) ß-catenin stained alveolar osteocytes. Scl-Ab had no effect on mineralized tissues of the tooth - dentin, enamel, acellular and cellular cementum. There was a non-significant trend toward increased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fibral structural parameters were not affected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in the Hyp mouse model of XLH.