Publications by authors named "A Rocha"

1,779 Publications

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Treatment administered to newborns with congenital syphilis during a penicillin shortage in 2015, Fortaleza, Brazil.

BMC Pediatr 2021 Apr 8;21(1):166. Epub 2021 Apr 8.

World Health Organization, Department of Sexual Reproductive Health and Research, Geneva, Switzerland.

Background: Between 2014 and 2016, Brazil experienced a severe shortage in penicillin supply, resulting in a lack of treatment among some pregnant women and newborns with syphilis and the use of non-evidence-based regimens. This study evaluated all live births in Fortaleza reported with CS in 2015 in order to identify the different therapeutic regimens used in newborns during this period of penicillin shortage.

Methods: A retrospective cross-sectional study design was conducted using manually extracted data from medical chart review of maternal and infant cases delivered in 2015 from all public maternity hospitals in the city of Fortaleza. Data collection occurred from June 2017 to July 2018.

Results: A total of 575 congenital syphilis cases were reported to the municipality of Fortaleza during 2015 and 469 (81.5%) were analyzed. Of these, only 210 (44.8%) were treated with a nationally-recommended treatment. As alternative therapeutic options, ceftriaxone was used in 65 (13.8%), Cefazolin in 15 (3.2%) and the combination of more than one drug in 179 (38.2%). Newborns with serum VDRL titers ≥1:16 (p = 0.021), who had some clinical manifestation at birth (p = 0.003), who were born premature (p <  0.001), with low birth weight (p = 0.010), with jaundice indicative of the need for phototherapy (p = 0.019) and with hepatomegaly (p = 0.045) were more likely to be treated with penicillin according to national treatment guidelines compared to newborns treated with other regimens.

Conclusion: During the period of shortage of penicillin in Fortaleza, less than half of the infants reported with CS were treated with a nationally-recommended regimen, the remaining received treatment with medications available in the hospital of birth including drugs that are not part of nationally or internationally-recommended treatment recommendations.
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http://dx.doi.org/10.1186/s12887-021-02619-xDOI Listing
April 2021

Impact of Different Physical Exercises on the Expression of Autophagy Markers in Mice.

Int J Mol Sci 2021 Mar 5;22(5). Epub 2021 Mar 5.

Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Avenida Bandeirantes, 3900, Monte Alegre, Ribeirão Preto 14040-907, Brazil.

Although physical exercise-induced autophagy activation has been considered a therapeutic target to enhance tissue health and extend lifespan, the effects of different exercise models on autophagy in specific metabolic tissues are not completely understood. This descriptive investigation compared the acute effects of endurance (END), exhaustive (ET), strength (ST), and concurrent (CC) physical exercise protocols on markers of autophagy, genes, and proteins in the gastrocnemius muscle, heart, and liver of mice. The animals were euthanized immediately (0 h) and six hours (6 h) after the acute exercise for the measurement of glycogen levels, mRNA expression of , , , , , , , , and protein levels of Beclin 1 and ATG5. The markers of autophagy were measured by quantifying the protein levels of LC3II and Sqstm1/p62 in response to three consecutive days of intraperitoneal injections of colchicine. In summary, for gastrocnemius muscle samples, the main alterations in mRNA expressions were observed after 6 h and for the ST group, and the markers of autophagy for the CC group were increased (i.e., LC3II and Sqstm1/p62). In the heart, the Beclin 1 and ATG5 levels were downregulated for the ET group. Regarding the markers of autophagy, the Sqstm1/p62 in the heart tissue was upregulated for the END and ST groups, highlighting the beneficial effects of these exercise models. The liver protein levels of ATG5 were downregulated for the ET group. After the colchicine treatment, the liver protein levels of Sqstm1/p62 were decreased for the END and ET groups compared to the CT, ST, and CC groups. These results could be related to diabetes and obesity development or liver dysfunction improvement, demanding further investigations.
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http://dx.doi.org/10.3390/ijms22052635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962017PMC
March 2021

Improvements in the Resistance of the Banana Species to Fusarium Wilt: A Systematic Review of Methods and Perspectives.

J Fungi (Basel) 2021 Mar 25;7(4). Epub 2021 Mar 25.

Embrapa Cassava and Fruit, Cruz das Almas 44380-000, Bahia, Brazil.

The fungus f. sp. (FOC), tropical race 4 (TR4), causes wilt of banana, a pandemic that has threatened the cultivation and export trade of this fruit. This article presents the first systematic review of studies conducted in the last 10 years on the resistance of spp. to wilt. We evaluated articles deposited in different academic databases, using a standardized search string and predefined inclusion and exclusion criteria. We note that the information on the sequencing of the sp. genome is certainly a source for obtaining resistant cultivars, mainly by evaluating the banana transcriptome data after infection with FOC. We also showed that there are sources of resistance to FOC race 1 (R1) and FOC TR4 in banana germplasms and that these data are the basis for obtaining resistant cultivars, although the published data are still scarce. In contrast, the transgenics approach has been adopted frequently. We propose harmonizing methods and protocols to facilitate the comparison of information obtained in different research centers and efforts based on global cooperation to cope with the disease. Thus, we offer here a contribution that may facilitate and direct research towards the production of banana resistant to FOC.
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http://dx.doi.org/10.3390/jof7040249DOI Listing
March 2021

Food Consumption Determinants and Barriers for Healthy Eating at the Workplace-A University Setting.

Foods 2021 Mar 25;10(4). Epub 2021 Mar 25.

GreenUPorto-Sustainable Agrifood Production Research Centre, Campus de Vairão Edifício de Ciências Agrárias (FCV2) Rua da Agrária, 747, 4485-646 Vairão, Portugal.

Background: A wide variety of social, cultural and economic factors may influence dietary patterns. This work aims to identify the main determinants of food consumption and barriers for healthy eating at the workplace, in a university setting.

Methods: A cross-sectional observational study was conducted with 533 participants. Data were obtained through the application of a self-administered questionnaire that included socio-demographic information, food consumption determinants and the main perceived barriers for healthy eating at the workplace.

Results: The respondents identified "price" (22.5%), "meal quality" (20.7%), and "location/distance" (16.5%). For women, the determinant "availability of healthy food options" was more important than for men ( < 0.001). The food consumption determinants at the workplace most referred to by respondents were related to the nutritional value. Smell, taste, appearance and texture, and good value for money, were also considered important for choosing food at the workplace. Respondents referred to work commitments and lack of time as the main barriers for healthy eating at the workplace.

Conclusions: Identification of determinants involved in food consumption, and the barriers for healthy eating, may contribute to a better definition of health promotion initiatives at the workplace aiming to improve nutritional intake.
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http://dx.doi.org/10.3390/foods10040695DOI Listing
March 2021

UV Inscription and Pressure Induced Long-Period Gratings through 3D Printed Amplitude Masks.

Sensors (Basel) 2021 Mar 11;21(6). Epub 2021 Mar 11.

Instituto de Telecomunicações, Campus Universitário de Santiago, University of Aveiro, 3810-193 Aveiro, Portugal.

In this work, we demonstrate for the first time the capability to inscribe long-period gratings (LPGs) with UV radiation using simple and low cost amplitude masks fabricated with a consumer grade 3D printer. The spectrum obtained for a grating with 690 µm period and 38 mm length presented good quality, showing sharp resonances (i.e., 3 dB bandwidth < 3 nm), low out-of-band loss (~0.2 dB), and dip losses up to 18 dB. Furthermore, the capability to select the resonance wavelength has been demonstrated using different amplitude mask periods. The customization of the masks makes it possible to fabricate gratings with complex structures. Additionally, the simplicity in 3D printing an amplitude mask solves the problem of the lack of amplitude masks on the market and avoids the use of high resolution motorized stages, as is the case of the point-by-point technique. Finally, the 3D printed masks were also used to induce LPGs using the mechanical pressing method. Due to the better resolution of these masks compared to ones described on the state of the art, we were able to induce gratings with higher quality, such as low out-of-band loss (0.6 dB), reduced spectral ripples, and narrow bandwidths (~3 nm).
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http://dx.doi.org/10.3390/s21061977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998659PMC
March 2021

Excessive downhill training leads to early onset of knee osteoarthritis.

Osteoarthritis Cartilage 2021 Mar 30. Epub 2021 Mar 30.

Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada; Biomechanics Laboratory, School of Sports, Federal University of Santa Catarina, Florianopolis, SC, Brazil. Electronic address:

Objective: Increased levels of pro-inflammatory cytokines are associated with the release of degradative enzymes leading to osteoarthritis (OA) development. Although physical exercise (PE) is generally recognized as beneficial for OA symptoms, excessive training workload and eccentric muscular exercise have increased OA risk. Here, we investigated the effects of excessive exercise workload and exercise type on systemic inflammation and knee joint OA.

Methods: Mice were divided into five groups: sedentary (SED), uphill training (TRU), downhill training (TRD), excessive uphill training (ETU), and excessive downhill training (ETD) for an eight-week training intervention protocol.

Results: ETD group had increased pro-inflammatory cytokines in serum, vastus lateralis (VL), and vastus medialis (VM) muscles, while ETU group mice had increased cytokine levels in the VL and VM. General knee joint OARSI scores were more significant in ETD group compared to TRU group. They were also more meaningful for the medial tibial plateau of ETD group compared to SED group. MMP-3 and cleaved Caspase-3 were higher in the ETD group than the SED and TRU group, while Adamts-5 was higher in the ETD group than the SED group. TRU group had increased PRG-4 levels compared to ETU and ETD group. ETD group had decreased total bone volume, trabecular bone volume, and cortical thickness compared to SED group.

Conclusion: Excessive downhill training induced a chronic pro-inflammatory state in mice and was associated with early signs of cartilage and bone degeneration that are clinical indicators of knee OA.
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http://dx.doi.org/10.1016/j.joca.2021.03.016DOI Listing
March 2021

Economic evaluation of CPAP therapy for obstructive sleep apnea: a scoping review and evidence map.

Sleep Breath 2021 Mar 31. Epub 2021 Mar 31.

Cochrane Brazil, São Paulo, Brazil.

Purpose: To synthesize findings of economic evaluations investigating cost-effectiveness of continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA) and of strategies of organization of care related to CPAP therapy.

Methods: Scoping review with searches conducted in MEDLINE, CRD, LILACS, and Embase in August 2020. Eligible studies were economic evaluations comparing CPAP to other alternative or assessing strategies of care for CPAP therapy. Results were presented narratively, and incremental cost-effectiveness ratios (ICER) were presented in evidence maps.

Results: Of 34 studies, 3 concluded that CPAP is less costly and more effective when compared to usual care. Most studies indicated that CPAP is associated with better health outcomes, but at higher prices. ICER ranged from USD 316 to 98,793 per quality-adjusted life years (QALY) gained (median 16,499; IQR 8267 to 33,119). One study concluded that CPAP is more costly and less effective, when treatment is applied to all patients, regardless of disease severity. Variability of ICER was mainly due to definition of population and applied time horizons. When CPAP was compared to mandibular advancement device, ICER ranged from USD 21,153 to 361,028 (median 89,671; IQR 26,829 to 295,983), which represents the investment in CPAP therapy required to obtain one extra QALY. Three studies assessed the effects of organizing CPAP therapy in primary care, which was cost-effective or cost-saving.

Conclusions: Compared to usual care, CPAP is cost-effective after the second year of treatment, when indicated for moderate-to-severe OSA. CPAP therapy may be even more cost-effective by using different strategies of organization of care. These findings may inform decision making related to CPAP reimbursement in health systems.

Clinical Trial Registration Number: Not applicable.
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http://dx.doi.org/10.1007/s11325-021-02362-8DOI Listing
March 2021

Interleukin-6 ablation does not alter morphofunctional heart characteristics but modulates physiological and inflammatory markers after strenuous exercise.

Cytokine 2021 Mar 23;142:155494. Epub 2021 Mar 23.

Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.

Interleukin-6 (IL-6) is associated with pathological cardiac hypertrophy and can be dramatically increased in serum after an acute strenuous exercise session. However, IL-6 is also associated with the increased production and release of anti-inflammatory cytokines and the inhibition of tumor necrosis factor-alpha (TNF-α) after chronic moderate exercise. To elucidate the relevance of IL-6 in inflammatory and hypertrophic signaling in the heart in response to an acute strenuous exercise session, we combined transcriptome analysis using the BXD mice database and exercised IL-6 knockout mice (IL-6KO). Bioinformatic analysis demonstrated that low or high-levels of Il6 mRNA in the heart did not change the inflammation- and hypertrophy-related genes in BXD mice strains. On the other hand, bioinformatic analysis revealed a strong positive correlation between Il6 gene expression in skeletal muscle with inflammation-related genes in cardiac tissue in several BXD mouse strains, suggesting that skeletal muscle-derived IL-6 could alter the heart's intracellular signals, particularly the inflammatory signaling. As expected, an acute strenuous exercise session increased IL-6 levels in wild-type, but not in IL-6KO mice. Despite not showing morphofunctional differences in the heart at rest, the IL-6KO group presented a reduction in physical performance and attenuated IL-6, TNF-α, and IL-1beta kinetics in serum, as well as lower p38MAPK phosphorylation, Ampkalpha expression, and higher Acta1 and Tnf gene expressions in the left ventricle in the basal condition. In response to strenuous exercise, IL-6 ablation was linked to a reduction in the pro-inflammatory response and higher activation of classical physiological cardiac hypertrophy proteins.
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http://dx.doi.org/10.1016/j.cyto.2021.155494DOI Listing
March 2021

Successful denosumab treatment for central giant cell granuloma in a 9-year-old child.

Spec Care Dentist 2021 Mar 24. Epub 2021 Mar 24.

Oral Medicine Department, AC Camargo Cancer Center, São Paulo, Brazil.

Background: Denosumab is a nonsurgical treatment option for central giant cell granulomas (CGCG), especially in aggressive lesions.

Case Report: We describe a 9-year-old girl with an aggressive maxillary CGCG successfully treated with denosumab, avoiding a mutilating surgery after intralesional corticosteroid injections failed, and the lesion continued to rapidly grow. During denosumab treatment, she developed a self-limiting area of osteonecrosis in the maxillary alveolar bone, which rapidly resolved after antibiotic therapy. Six months after denosumab discontinuation, a maxillary surgical recontour was performed. Two weeks after surgery, the patient presented vomiting, pallor, dehydration, but no fever. Blood tests revealed severe hypercalcemia and acute renal dysfunction. After discarding thyroid, parathyroid, and adrenal alterations, a diagnosis of severe rebound hypercalcemia after denosumab treatment was made. Treatment consisted of hyperhydration, calcium pamidronate, and methylprednisolone, restoring calcium levels to normal.

Conclusion: After 2 years of follow-up, she remains on orthodontic treatment, with no recurrences or other episodes of hypercalcemia.
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http://dx.doi.org/10.1111/scd.12588DOI Listing
March 2021

The functional impact of nuclear reorganization in cellular senescence.

Brief Funct Genomics 2021 Mar 23. Epub 2021 Mar 23.

Associate Professor in the Department of Molecular Biology, Cell Biology and Biochemistry at Brown University.

Cellular senescence is the irreversible cell cycle arrest in response to DNA damage. Because senescent cells accumulate with age and contribute to chronic inflammation, they are promising therapeutic targets for healthspan extension. The senescent phenotype can vary depending on cell type and on the specific insults that induce senescence. This variability is also reflected in the extensive remodeling of the genome organization within the nucleus of senescent cells. Here, we give an overview of the nuclear changes that occur in different forms of senescence, including changes to chromatin state and composition and to the three-dimensional organization of the genome, as well as alterations to the nuclear envelope and to the accessibility of repetitive genomic regions. Many of these changes are shared across all forms of senescence, implicating nuclear organization as a fundamental driver of the senescent state and of how senescent cells interact with the surrounding tissue.
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http://dx.doi.org/10.1093/bfgp/elab012DOI Listing
March 2021

Clinical treatment for HCV infection reverses CYP2C19 inhibition.

Br J Clin Pharmacol 2021 Mar 19. Epub 2021 Mar 19.

Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

Aim: Infection by the hepatitis C virus (HCV) generates inflammatory response selectively modulating CYP activities. This study assessed the effect of chronic hepatitis C on CYP2C19 activity in patients with HCV.

Methods: Patients with HCV infection (n = 23) at different fibrosis stages were allocated into groups 1 (F0/F1 and F2, mild to moderate fibrosis) and 2 (F3 and F4, advanced fibrosis stages). Phase 1 was conducted before the treatment with direct-acting antivirals (DAAs), and Phase 2 after the sustained virological response. Participants were administered 2 mg single oral dose of omeprazole (OME) as probe a drug in both phases. Metabolic ratios (MR) (plasma samples collected at 4 h after OME administration) were calculated dividing plasma concentrations of 5-hydroxyomeprazole by OME.

Results: The MR's for group 1 were 0.45 (0.34-0.60, 90% CI) and 0.69 (0.50-0.96) for phases 1 and 2, respectively; while the MR's for group 2 were 0.25 (0.21-0.31) and 0.41 (0.30-0.56) for phases 1 and 2, respectively. MR's were different (p < 0.05) between phases 1 and 2 for both groups, as well as between groups 1 and 2 in phase 1, but not in phase 2 (p > 0.05).

Conclusion: Both groups presented different MR's before and after treatment with DAAs, evidencing that CYP2C19 inhibition during inflammation was at least partially reversed after DAAs treatment. Groups 1 and 2 were also found different in phase 1 but not phase 2, showing that CYP2C19 metabolic activity does not differ between groups after DAAs treatment.
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http://dx.doi.org/10.1111/bcp.14829DOI Listing
March 2021

Recovery of Synthetic Zika Virus Based on Rio-U1 Isolate Using a Genetically Stable Two Plasmid System and cDNA Amplification.

Front Microbiol 2021 24;12:639655. Epub 2021 Feb 24.

Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

In 2016, the world experienced the unprecedented Zika epidemic. The ZIKV emerged as a major human pathogen due to its association with the impairment of perinatal development and Guillain-Barré syndrome. The occurrence of these severe cases of Zika points to the significance of studies for understanding the molecular determinants of flavivirus pathogenesis. Reverse genetics is a powerful method for studying the replication and determinants of pathogenesis, virulence, and viral attenuation of flaviviruses, facilitating the design of vaccines and therapeutics. However, the main hurdle in the development of infectious clones is the instability of full-length cDNA in . Here, we described the development of a genetically stable and efficient infectious clone based on the ZIKV Rio-U1 isolated in the 2016 epidemic in Brazil. The employed strategy consisted of cloning the viral cDNA genome into two stable plasmid subclones and obtaining a high-quality cDNA template with increment in DNA mass for transcription by PCR amplification. The strategy for developing a ZIKV infectious cDNA clone designed in this study was successful, yielding a replicative and efficient clone-derived virus with high similarities with its parental virus, Rio-U1, by comparison of the proliferation capacity in mammal and insect cells. The infection of AG129 immunocompromised mice caused identical mortality rates, with similar disease progression and morbidity in the animals infected with the parental and the cDNA-derived virus. Histopathological analyses of mouse brains infected with the parental and the cDNA-derived viruses revealed a similar pathogenesis degree. We observed meningoencephalitis, cellular pyknosis, and neutrophilic invasion adjacent to the choroid plexus and perivascular cuffs with the presence of neutrophils. The developed infectious clone will be a tool for genetic and functional studies and to understand viral infection and pathogenesis better.
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http://dx.doi.org/10.3389/fmicb.2021.639655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943741PMC
February 2021

Surgical Management of Palatal Pleomorphic Adenoma (PPA) Recurrence After 10 years, Treated at a Brazilian Center - A Case Report.

Ann Maxillofac Surg 2020 Jul-Dec;10(2):533-536. Epub 2020 Dec 23.

Department of Radiation Oncology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.

Pleomorphic adenoma, considered the most frequent benign mixed neoplasm of the minor salivary glands, occurs mainly in the region of the hard palate, with slight predilection in females and peak of incidence between the third and fifth decades of life. An increase in recurrence rates has been associated with the histopathological variants of the tumor, cellular characteristics, stroma, and capsule rupture during surgical removal of the lesion. The present case report aims to describe the surgical approach performed on the patient, a 45-year-old woman with a recurrent Pleomorphic Adenoma (PA) in the region of the hard palate on the right side, 10 years after initial enucleation of the lesion; her main complaint was an increase in volume in the palatal region. After extensive local surgical excision of the tumor and 2 years of follow-up, there were no signs of recurrence. Computed tomography and a correct histopathological diagnosis are essential to enable the establishment of an appropriate surgical treatment, with the purpose of achieving complete removal of the lesion, with wide surgical margins, including the lining mucosa and the underlying periosteum, as described in the present case.
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http://dx.doi.org/10.4103/ams.ams_107_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944004PMC
December 2020

The ADC API: A Web API for the Programmatic Query of the AIRR Data Commons.

Front Big Data 2020 17;3:22. Epub 2020 Jun 17.

Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX, United States.

The Adaptive Immune Receptor Repertoire (AIRR) Community is a research-driven group that is establishing a clear set of community-accepted data and metadata standards; standards-based reference implementation tools; and policies and practices for infrastructure to support the deposit, curation, storage, and use of high-throughput sequencing data from B-cell and T-cell receptor repertoires (AIRR-seq data). The AIRR Data Commons is a distributed system of data repositories that utilizes a common data model, a common query language, and common interoperability formats for storage, query, and downloading of AIRR-seq data. Here is described the principal technical standards for the AIRR Data Commons consisting of the AIRR Data Model for repertoires and rearrangements, the AIRR Data Commons (ADC) API for programmatic query of data repositories, a reference implementation for ADC API services, and tools for querying and validating data repositories that support the ADC API. AIRR-seq data repositories can become part of the AIRR Data Commons by implementing the data model and API. The AIRR Data Commons allows AIRR-seq data to be reused for novel analyses and empowers researchers to discover new biological insights about the adaptive immune system.
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http://dx.doi.org/10.3389/fdata.2020.00022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931935PMC
June 2020

Polyphenols and Brazilian red propolis incorporated into a total-etching adhesive system help in maintaining bonding durability.

Heliyon 2021 Feb 19;7(2):e06237. Epub 2021 Feb 19.

Department of Chemistry, Federal Institute of Alagoas, Rua Mizael Domingues, 75, Campus Maceió, CEP 57020-600, Maceió, Alagoas, Brazil.

Objectives: The aim of this study was to evaluate the degree of conversion and bond strength of a commercial dental adhesive modified by the incorporation of quercetin, resveratrol (RES), and Brazilian red propolis (BRP).

Methods: BRP markers were identified using ultra-performance liquid chromatography coupled with a diode array detector, and the antioxidant activity (AAO) of the three substances was analyzed. Single Bond 2 adhesive (3M ESPE) was modified by adding BRP, quercetin, and RES, separately, at 20 μg/mL, 250 μg/mL, and 500 μg/mL, respectively. The degree of conversion (DC) was measured using near-infrared spectroscopy 24 h after photopolymerization. Measurements of the resin-dentin microtensile bond strength (μTBS) were carried out after 1 day and 1 year. Student's t test and ANOVA with Tukey's test were used for data analysis (α = 0.05).

Results: The markers daidzein, liquiritigenin, pinobanksin, isoliquiritigenin, formononetin, pinocembrin, and biochanin A were found in the ethanolic extract of BRP. Quercetin, RES, and BRP showed high AAO. The DC of the tested adhesives remained adequate for this category of material, with a slight increase in the DC of adhesives with quercetin and BRP ( > 0.05). Comparisons between μTBS measurements made at 1 day and 1 year showed that, contrary to the control group, μTBS values for all modified adhesives were maintained after 1 year in distilled water ( > 0.05).

Conclusions: These findings suggest that quercetin, RES, or BRP might be useful in adhesive dentistry to help improve hybrid layer resistance.

Clinical Significance: Dentin bonding agents with quercetin, RES, and BRP have potential to increase the longevity of composite restorations.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898005PMC
February 2021

Intraosseous neurilemoma of the mandible with unusual multilocular presentation: a case report.

Gen Dent 2021 Mar-Apr;69(2):28-32

This case report describes an intraosseous neurilemoma, observed radiographically as a multilocular lesion, in a 12-year-old patient. Physical examination revealed facial asymmetry, swelling on the right side of the mandibular body, and bone expansion in the region of the base of the buccal sulcus. Panoramic radiography revealed a multilocular radiolucency on the right side of the mandibular body in the periapical region extending from the distal region of the first premolar root to the second molar and adjacent to the third molar. Evaluation of a radiograph obtained 3 years earlier for an orthodontic assessment revealed that the lesion was present, appearing as a unilocular radiolucency near the root of the mandibular right first molar. An incisional biopsy of the multilocular lesion was performed, and Antoni A and Antoni B histologic patterns were identified by microscopic analysis. Immunohistochemical analysis was conducted, and neoplastic cells stained positive for the S-100 protein. The patient underwent conservative surgical excision of the lesion, and no recurrence was observed during 7 years of clinical follow-up. Based on analysis of the present case and previous cases reported in the literature, intraosseous neurilemoma, especially its multilocular variant, is an uncommon neoplasm. In the present case, evaluation of the lesion when it was first radiographically detectable, prior to orthodontic treatment, would have permitted a more limited surgical approach for the excision of a small intraosseous lesion.
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March 2021

Case Report: Intrapulmonary Arteriovenous Anastomoses in COVID-19-Related Pulmonary Vascular Changes: A New Player in the Arena?

Front Med (Lausanne) 2021 9;8:639152. Epub 2021 Feb 9.

Cardiothoracic and Vascular Division, Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Up to now, COVID-19-related vascular changes were mainly described as thrombo-embolic events. A handful of researchers reported another type of vascular abnormality referred to as "vascular thickening" or "vascular enlargement," without specifying whether the dilated vessels are arteries or veins nor providing a physiopathological hypothesis. Our observations indicate that the vascular dilatation occurs in the venous compartment, and underlying mechanisms might include increased blood flow due to inflammation and the activation of arteriovenous anastomoses.
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http://dx.doi.org/10.3389/fmed.2021.639152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900139PMC
February 2021

Paclitaxel mitigates structural alterations and cardiac conduction system defects in a mouse model of Hutchinson-Gilford progeria syndrome.

Cardiovasc Res 2021 Feb 24. Epub 2021 Feb 24.

Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.

Aims: Hutchinson-Gilford progeria syndrome (HGPS) is an ultrarare laminopathy caused by expression of progerin, a lamin A variant, also present at low levels in non-HGPS individuals. HGPS patients age and die prematurely, predominantly from cardiovascular complications. Progerin-induced cardiac repolarization defects have been described previously, although the underlying mechanisms are unknown.

Methods And Results: We conducted studies in heart tissue from progerin-expressing LmnaG609G/G609G (G609G) mice, including microscopy, intracellular calcium dynamics, patch-clamping, in vivo magnetic resonance imaging, and electrocardiography. Mouse G609G cardiomyocytes showed tubulin-cytoskeleton disorganization, t-tubular system disruption, sarcomere shortening, altered excitation-contraction coupling, and reductions in ventricular thickening and cardiac index. G609G mice exhibited severe bradycardia, and significant alterations of atrio-ventricular conduction and repolarization. Most importantly, 50% of G609G mice had altered heart rate variability, and sinoatrial block, both significant signs of premature cardiac aging. G609G cardiomyocytes had electrophysiological alterations which result in an elevated action potential plateau and early afterdepolarization bursting, reflecting slower sodium current inactivation and long Ca+2 transient duration, which may also help explain the mild QT prolongation in some HGPS patients. Chronic treatment with low-dose paclitaxel ameliorated structural and functional alterations in G609G hearts.

Conclusions: Our results demonstrate that tubulin-cytoskeleton disorganization in progerin-expressing cardiomyocytes causes structural, cardiac conduction and excitation-contraction coupling defects, all of which can be partially corrected by chronic treatment with low-dose of paclitaxel.
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http://dx.doi.org/10.1093/cvr/cvab055DOI Listing
February 2021

Primary conjunctival sporotrichosis in three cats from Northeastern Brazil.

Vet Ophthalmol 2021 Mar 19;24(2):209-215. Epub 2021 Feb 19.

Departamento de Morfologia e Fisiologia Animal, Universidade Federal Rural de Pernambuco, Brasil.

Introduction: Classically, sporotrichosis occurs as a chronic granulomatous lymphocutaneous infection. The extracutaneous form is uncommon and may affect the eye without cutaneous involvement. The most frequent form of ocular sporotrichosis reported in humans is a granulomatous conjunctivitis. There are no previous reports on primary ocular sporotrichosis in cats.

Procedures: Three mixed breed cats rescued from shelters were referred by the veterinarian for ophthalmic evaluation with a complaint of conjunctivitis nonresponsive to treatment with no evidence of skin disease or systemic disease. Complete ophthalmic examination, conjunctival cytology, and microbiological analysis were performed.

Results: Ophthalmic examinations revealed epiphora, purulent ocular discharge, conjunctival hyperemia, and a mass in the palpebral conjunctiva. Conjunctival cytology revealed segmented and degenerated neutrophils, conjunctival epithelial cells, and an abundant number of round and oval cells compatible with Sporothrix spp. Microbiological culture was performed and confirmed the presence of fungi from the Sporothrix schenckii complex. All animals were treated with oral itraconazole; two animals received topical itraconazole in association with oral treatment. Case 1 was refractory to treatment, and iodate potassium was combined with itraconazole therapy without resolution at the time of this publication. Cases 2 and 3 had complete resolution of conjunctival lesions with four months of oral and topical itraconazole therapy.

Conclusion: Conjunctival sporotrichosis should be considered as a differential diagnosis of conjunctivitis in cats from endemic regions. Conjunctival cytology is an important tool that can aid early diagnosis.
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http://dx.doi.org/10.1111/vop.12865DOI Listing
March 2021

Assessment of potters' occupational exposure to lead and associated risk factors in Maragogipinho, Brazil: preliminary results.

Int Arch Occup Environ Health 2021 Feb 19. Epub 2021 Feb 19.

Laboratory of Toxicology, College of Pharmacy, Federal University of Bahia, Av. Barão de Jeremoabo s/n. Ondina, Salvador, Bahia, 40170-115, Brazil.

Background And Purpose: Lead (Pb) is used as a flux in the glazing process of pottery utensils in several regions of the world. It can affect the nervous and hematopoietic systems; in addition, it is classified as a probable human carcinogen. This work aims to evaluate Pb exposure of potters and describe the main determinants of elevated blood Pb (PbB) levels in this group of workers.

Methods: This is a cross-sectional study with potters of Maragogipinho Village, Bahia, Brazil, of both sexes, aged 16-72 years (n = 85). Non-exposed workers of the same age range residing in the urban area of Aratuípe town were also recruited (n = 50). We evaluated Pb dust deposition rates (PbDrt) in pottery workshops and PbB levels. All Pb measurements were performed by Graphite Furnace Atomic Absorption Spectrometry.

Results: The median of PbB (min-max) and geometric mean (SD) PbDrt for the exposed group were 7.9 (0.9-49.8) µg/dL and 1463 (± 290,000) μg/m/30 days, respectively. For the control group, levels were 1.5 (0.1-19.8) μg/dL and 82 (46) μg/m 30 days, respectively.

Conclusion: The data found showed an excessive exposure among artisans, exceeding occupationally safe levels and those reported in the literature. It is important to implement occupational hygiene measures and improvements of the working conditions of these labors, especially the replacement of lead oxide in the pottery-glazing process.
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http://dx.doi.org/10.1007/s00420-021-01659-1DOI Listing
February 2021

Left Ventricular Concentric Geometric Patterns Are Associated With Worse Prognosis Among Patients With Type-A Aortic Dissection.

J Am Heart Assoc 2021 Feb 18;10(5):e018273. Epub 2021 Feb 18.

Department of Internal Medicine School of Medical Sciences State University of Campinas São Paulo Brazil.

Background This study compared left ventricular (LV) characteristics between patients with type-A and type-B aortic dissection (AD) and evaluated the ability of LV remodeling phenotypes (hypertrophy, concentricity, or geometric patterns) to predict mortality in both AD types. Methods and Results We evaluated 236 patients with type A and 120 patients with type B who had echocardiograms within 60 days before or after AD diagnosis (median [25th, 75th percentiles] time difference between echocardiogram and AD diagnosis=1 [0, 6] days) from 3 centers. Patients were stratified according to LV phenotypes, and early (90-day) and late (1-year) mortality after AD diagnosis were assessed. In adjusted logistic regression analysis, patients with type A had higher and lower odds of concentric and eccentric hypertrophy (odds ratio [OR], 2.56; 95% CI, 1.50-4.36; <0.001; and OR, 0.55; 95% CI, 0.31-0.97; =0.039, respectively) than those with type B. Results of multivariable Cox-regression analysis showed that LV remodeling phenotypes were not related to mortality in patients with type B. By contrast, LV concentricity was associated with greater early and late mortality (hazard ratio [HR], 2.22; 95% CI, 1.24-3.96; =0.007 and HR, 2.06; 95% CI, 1.20-3.54; =0.009, respectively) in type A. In further analysis considering normal LV geometry as reference, LV concentric remodeling and concentric hypertrophy were associated with early mortality (HR, 7.78; 95% CI, 2.35-25.78; <0.001 and HR, 4.38; 95% CI, 1.47-13.11; =0.008, respectively), whereas concentric remodeling was associated with late mortality (HR, 5.40; 95% CI, 1.91-15.26; <0.001) among patients with type A. Assessment of LV geometric patterns and concentricity provided incremental prognostic value in predicting early and late mortality beyond clinical variables in patients with type A based on net reclassification improvement and integrated discrimination improvement. Conclusions LV geometric patterns derived from LV concentricity were associated with greater mortality among patients with type A and may be markers of adverse prognosis in this population.
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http://dx.doi.org/10.1161/JAHA.120.018273DOI Listing
February 2021

One Bout of Aerobic Exercise Can Enhance the Expression of in Oxidative Skeletal Muscle Samples.

Front Physiol 2021 1;12:626096. Epub 2021 Feb 1.

School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, Brazil.

The nuclear receptor subfamily 1, group D member 1 (, plays a role in the skeletal muscle's oxidative capacity, mitochondrial biogenesis, atrophy genes, and muscle fiber size. In light of the effects of physical exercise, the present study investigates the acute response of and genes related to atrophy and mitochondrial biogenesis on endurance and resistance exercise protocols. In this investigation, we observed, after one bout of endurance exercise, an upregulation of in soleus muscle, but not in the gastrocnemius, and some genes related to mitochondrial biogenesis and atrophy were enhanced as well. Also, analysis of muscle transcripts from diverse isogenic BXD mice families revealed that the strains with higher gene expression displayed upregulation of AMPK signaling and mitochondrial-related genes. In summary, a single session of endurance exercise can enhance the mRNA levels in an oxidative muscle.
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http://dx.doi.org/10.3389/fphys.2021.626096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882602PMC
February 2021

Dynamics of a Dual SARS-CoV-2 Lineage Co-Infection on a Prolonged Viral Shedding COVID-19 Case: Insights into Clinical Severity and Disease Duration.

Microorganisms 2021 Feb 2;9(2). Epub 2021 Feb 2.

CHUSJ-Centro Hospitalar Universitário S. João, 4200-319 Porto, Portugal.

A few molecularly proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases of symptomatic reinfection are currently known worldwide, with a resolved first infection followed by a second infection after a 48 to 142-day intervening period. We report a multiple-component study of a clinically severe and prolonged viral shedding coronavirus disease 2019 (COVID-19) case in a 17-year-old Portuguese female. She had two hospitalizations, a total of 19 RT-PCR tests, mostly positive, and criteria for releasing from home isolation at the end of 97 days. The viral genome was sequenced in seven serial samples and in the diagnostic sample from her infected mother. A human genome-wide array (>900 K) was screened on the seven samples, and in vitro culture was conducted on isolates from three late samples. The patient had co-infection by two SARS-CoV-2 lineages, which were affiliated in distinct clades and diverging by six variants. The 20A lineage was absolute at the diagnosis (shared with the patient's mother), but nine days later, the 20B lineage had 3% frequency, and two months later, the 20B lineage had 100% frequency. The 900 K profiles confirmed the identity of the patient in the serial samples, and they allowed us to infer that she had polygenic risk scores for hospitalization and severe respiratory disease within the normal distributions for a Portuguese population cohort. The early-on dynamic co-infection may have contributed to the severity of COVID-19 in this otherwise healthy young patient, and to her prolonged SARS-CoV-2 shedding profile.
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http://dx.doi.org/10.3390/microorganisms9020300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912897PMC
February 2021

Link Prediction Based on Stochastic Information Diffusion.

IEEE Trans Neural Netw Learn Syst 2021 Feb 4;PP. Epub 2021 Feb 4.

Link prediction (LP) in networks aims at determining future interactions among elements; it is a critical machine-learning tool in different domains, ranging from genomics to social networks to marketing, especially in e-commerce recommender systems. Although many LP techniques have been developed in the prior art, most of them consider only static structures of the underlying networks, rarely incorporating the network's information flow. Exploiting the impact of dynamic streams, such as information diffusion, is still an open research topic for LP. Information diffusion allows nodes to receive information beyond their social circles, which, in turn, can influence the creation of new links. In this work, we analyze the LP effects through two diffusion approaches, susceptible-infected-recovered and independent cascade. As a result, we propose the progressive-diffusion (PD) method for LP based on nodes' propagation dynamics. The proposed model leverages a stochastic discrete-time rumor model centered on each node's propagation dynamics. It presents low-memory and low-processing footprints and is amenable to parallel and distributed processing implementation. Finally, we also introduce an evaluation metric for LP methods considering both the information diffusion capacity and the LP accuracy. Experimental results on a series of benchmarks attest to the proposed method's effectiveness compared with the prior art in both criteria.
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http://dx.doi.org/10.1109/TNNLS.2021.3053263DOI Listing
February 2021

Cardiac phenotype in familial partial lipodystrophy.

Clin Endocrinol (Oxf) 2021 Jan 27. Epub 2021 Jan 27.

Division of Metabolism, Endocrinology and Diabetes (MEND), Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.

Objectives: LMNA variants have been previously associated with cardiac abnormalities independent of lipodystrophy. We aimed to assess cardiac impact of familial partial lipodystrophy (FPLD) to understand the role of laminopathy in cardiac manifestations.

Study Design: Retrospective cohort study.

Methods: Clinical data from 122 patients (age range: 13-77, 101 females) with FPLD were analysed. Mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with an LMNA variant were studied as proof-of-concept for future studies.

Results: Subjects with LMNA variants had a higher prevalence of overall cardiac events than others. The likelihood of having an arrhythmia was significantly higher in patients with LMNA variants (OR: 3.77, 95% CI: 1.45-9.83). These patients were at higher risk for atrial fibrillation or flutter (OR: 5.78, 95% CI: 1.04-32.16). The time to the first arrhythmia was significantly shorter in the LMNA group, with a higher HR of 3.52 (95% CI: 1.34-9.27). Non-codon 482 LMNA variants were more likely to be associated with cardiac events (vs. 482 LMNA: OR: 4.74, 95% CI: 1.41-15.98 for arrhythmia; OR: 17.67, 95% CI: 2.45-127.68 for atrial fibrillation or flutter; OR: 5.71, 95% CI: 1.37-23.76 for conduction disease). LMNA mutant hiPSC-CMs showed a higher frequency of spontaneous activity and shorter action potential duration. Functional syncytia of hiPSC-CMs displayed several rhythm alterations such as early afterdepolarizations, spontaneous quiescence and spontaneous tachyarrhythmia, and significantly slower recovery in chronotropic changes induced by isoproterenol exposure.

Conclusions: Our results highlight the need for vigilant cardiac monitoring in FPLD, especially in patients with LMNA variants who have an increased risk of developing cardiac arrhythmias. In addition, hiPSC-CMs can be studied to understand the basic mechanisms for the arrhythmias in patients with lipodystrophy to understand the impact of specific mutations.
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http://dx.doi.org/10.1111/cen.14426DOI Listing
January 2021

Long term mortality of patients with Parkinson's disease treated with deep brain stimulation in a reference center.

Clin Neurol Neurosurg 2021 Mar 12;202:106486. Epub 2021 Jan 12.

Faculty of Medicine, Porto University, Portugal; Neurosurgery Department, Centro Hospitalar Universitário De São João E.P.E., Porto, Portugal.

Introduction: Parkinson's disease (PD) is a common neurodegenerative disorder, with a higher risk of death than general population. Deep Brain Stimulation (DBS) has been used to treat PD for more than 2 decades, but few studies exist concerning mortality in this subset of patients. Our goal is to analyse mortality in PD patients treated with DBS in our centre.

Methods: retrospective evaluation of clinical files of patients with PD who underwent DBS surgery consecutively between October 2002 and May 2019.

Results: 346 patients were included in the analysis, 60 % male, with a mean age at disease onset of 48± 8 years (18-64), mean age at surgery of 60 ± 7 years (33-75), and mean disease duration until surgery of 14 ± 6 years (3-52). Mean follow-up after surgery was 7 ± 4 years (range 1-17). Overall mortality rate was 17.9 % and mean age at time of death was 71 ± 6 years. The main causes of death were pneumonia, dementia and acute myocardial infarction. In our series, male gender and disease duration until surgery were the only predictors of mortality in multivariate analysis.

Conclusion: Our study showed a long-term survival higher than previously described, and suggests that the treatment of patients with shorter disease evolution might have a survival benefit. The leading causes of death in PD patients treated with DBS seems unrelated to surgery, as the main causes of death are comparable to non-DBS patients.
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http://dx.doi.org/10.1016/j.clineuro.2021.106486DOI Listing
March 2021

Neuroradiologic Phenotyping of Galactosemia: From the Neonatal Form to the Chronic Stage.

AJNR Am J Neuroradiol 2021 03 21;42(3):590-596. Epub 2021 Jan 21.

Neuroradiology Department, (A.L.P., F.T.P., A.J.d.R., L.L.F.d.A.), Hospital da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil.

Galactosemia is a rare genetic condition caused by mutation of enzymes involved in galactose and glucose metabolism. The varying clinical spectrum reflects the genetic complexity of this entity manifesting as acute neonatal toxicity syndrome, requiring prompt diagnosis and treatment, to more insidious clinical scenarios as observed in the subacute and chronic presentations. The current literature predominantly focuses on the long-standing sequelae of this disease. The purpose of this multicenter clinical report comprising 17 patients with galactosemia is to highlight the MR imaging patterns encompassing the whole spectrum of galactosemia, emphasizing the 3 main clinical subtypes: 1) acute neonatal presentation, with predominant white matter edema; 2) subacute clinical onset with a new finding called the "double cap sign"; and 3) a chronic phase of the disease with heterogeneous imaging findings. The knowledge of these different patterns together with MR spectroscopy and the clinical presentation may help in prioritizing galactosemia over other neonatal metabolic diseases and prevent possible complications.
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http://dx.doi.org/10.3174/ajnr.A7016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959436PMC
March 2021

Covid-19 Automated Diagnosis and Risk Assessment through Metabolomics and Machine Learning.

Anal Chem 2021 02 20;93(4):2471-2479. Epub 2021 Jan 20.

Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Cidade Universitária Zeferino Vaz, Campinas, São Paulo 350-13083-970, Brazil.

COVID-19 is still placing a heavy health and financial burden worldwide. Impairment in patient screening and risk management plays a fundamental role on how governments and authorities are directing resources, planning reopening, as well as sanitary countermeasures, especially in regions where poverty is a major component in the equation. An efficient diagnostic method must be highly accurate, while having a cost-effective profile. We combined a machine learning-based algorithm with mass spectrometry to create an expeditious platform that discriminate COVID-19 in plasma samples within minutes, while also providing tools for risk assessment, to assist healthcare professionals in patient management and decision-making. A cross-sectional study enrolled 815 patients (442 COVID-19, 350 controls and 23 COVID-19 suspicious) from three Brazilian epicenters from April to July 2020. We were able to elect and identify 19 molecules related to the disease's pathophysiology and several discriminating features to patient's health-related outcomes. The method applied for COVID-19 diagnosis showed specificity >96% and sensitivity >83%, and specificity >80% and sensitivity >85% during risk assessment, both from blinded data. Our method introduced a new approach for COVID-19 screening, providing the indirect detection of infection through metabolites and contextualizing the findings with the disease's pathophysiology. The pairwise analysis of biomarkers brought robustness to the model developed using machine learning algorithms, transforming this screening approach in a tool with great potential for real-world application.
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http://dx.doi.org/10.1021/acs.analchem.0c04497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023531PMC
February 2021

Whole-body senescent cell clearance alleviates age-related brain inflammation and cognitive impairment in mice.

Aging Cell 2021 02 20;20(2):e13296. Epub 2021 Jan 20.

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.

Cellular senescence is characterized by an irreversible cell cycle arrest and a pro-inflammatory senescence-associated secretory phenotype (SASP), which is a major contributor to aging and age-related diseases. Clearance of senescent cells has been shown to improve brain function in mouse models of neurodegenerative diseases. However, it is still unknown whether senescent cell clearance alleviates cognitive dysfunction during the aging process. To investigate this, we first conducted single-nuclei and single-cell RNA-seq in the hippocampus from young and aged mice. We observed an age-dependent increase in p16 senescent cells, which was more pronounced in microglia and oligodendrocyte progenitor cells and characterized by a SASP. We then aged INK-ATTAC mice, in which p16 -positive senescent cells can be genetically eliminated upon treatment with the drug AP20187 and treated them either with AP20187 or with the senolytic cocktail Dasatinib and Quercetin. We observed that both strategies resulted in a decrease in p16 exclusively in the microglial population, resulting in reduced microglial activation and reduced expression of SASP factors. Importantly, both approaches significantly improved cognitive function in aged mice. Our data provide proof-of-concept for senolytic interventions' being a potential therapeutic avenue for alleviating age-associated cognitive impairment.
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http://dx.doi.org/10.1111/acel.13296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884042PMC
February 2021