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The aim of the study is to expound the effect of psoriasis on salivary glands by evaluating the secretion of saliva and salivary cytokine biomarkers in patients with psoriasis. This study was conducted by recruiting 120 subjects that included 60 patients diagnosed clinically with active psoriasis and 60 healthy controls who were age and gender matched to psoriatic subjects. Unstimulated whole saliva was collected from all the subjects by spitting method, and levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-2 (IL-2), and IL-10 (IL-10) were determined via enzyme-linked immunosorbent assay (BT Lab, Shanghai, China). Secretion of saliva in psoriasis patients was considerably reduced than in healthy controls. The concentrations of pro-inflammatory cytokines (TNF-α, IFN-γ, and IL-2) were significantly increased, whereas level of anti-inflammatory cytokine (IL-10) was markedly decreased in the saliva of psoriasis patients with hyposalivation compared to healthy subjects. Our results demonstrated significant negative correlation of salivary flow rates with the disease severity. No significant correlations were obtained between salivary levels of tested cytokines and salivary flow rates in our study. Findings of the study reflect inflammation of salivary glands with reduced salivary flow rates in psoriasis patients. The inflammatory responses in salivary gland tissues by virtue of increased pro-inflammatory cytokines concentrations together with lower anti-inflammatory cytokine levels may have a role in affecting the saliva secretion in psoriasis patients. Secretion of unstimulated saliva in psoriasis patients decreases with the severity and duration of the disease.
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A carefully designed daylight collector for a tubular skylight is necessary to serve the occupants' illumination needs under the dynamic trajectory of the sun. This work simulated an improved configuration of a passive daylight collector comprising parabolic and conical reflectors in a modeled room using the lighting software tool TracePro. Results indicated that the lighting performance of the proposed design configuration was significantly enhanced under low altitude sun in comparison with conventional tubular skylights (with revolved parabolic and cylindrical reflectors) [Light. Res. Technol.52, 495 (2020)10.1177/1477153519872794] and hemispherical transparent dome as daylight collectors by more than â¼30%-40% and â¼110%-130%, respectively.
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Nucleic acid amplification tests (NAATs) are the primary means of identifying acute infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Accurate and fast test results may permit more efficient use of protective and isolation resources and allow rapid therapeutic interventions. We evaluated the analytical and clinical performance characteristics of the Xpert Xpress SARS-CoV-2 (Xpert) test, a rapid, automated molecular test for SARS-CoV-2. Analytical sensitivity and specificity/interference were assessed with infectious SARS-CoV-2; other infectious coronavirus species, including SARS-CoV; and 85 nasopharyngeal swab specimens positive for other respiratory viruses, including endemic human coronaviruses (hCoVs). Clinical performance was assessed using 483 remnant upper- and lower-respiratory-tract specimens previously analyzed by standard-of-care (SOC) NAATs. The limit of detection of the Xpert test was 0.01 PFU/ml. Other hCoVs, including Middle East respiratory syndrome coronavirus, were not detected by the Xpert test. SARS-CoV, a closely related species in the subgenus Sarbecovirus, was detected by a broad-range target (E) but was distinguished from SARS-CoV-2 (SARS-CoV-2-specific N2 target). Compared to SOC NAATs, the positive agreement of the Xpert test was 219/220 (99.5%), and the negative agreement was 250/261 (95.8%). A third tie-breaker NAAT resolved all but three of the discordant results in favor the Xpert test. The Xpert test provided sensitive and accurate detection of SARS-CoV-2 in a variety of upper- and lower-respiratory-tract specimens. The high sensitivity and short time to results of approximately 45 min may impact patient management.
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Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Pneumonia Viral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Automação Laboratorial/métodos , Betacoronavirus/genética , COVID-19 , Teste para COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2 , Sensibilidade e Especificidade , Adulto JovemRESUMO
Background: Cytopathology is defined as a branch of pathology which involves studying diseases and their diagnosis. The conventional method involves fixing the cells in alcohol, but its poor availability in ill-equipped areas can pose problems. One solution to this problem is air-drying of smears followed by rehydration. In this study, we intend to assess the cytomorphologic changes in air-dried smears rehydrated using various agents and to correlate them with the smears prepared using conventional wet technique. Also, we attempt to find the alternative to alcohol which can be used in less equipped areas. Materials and Methods: Three smears each were prepared from 24 patients (12 healthy and 12 with habits). A total of 72 smears were prepared. One smear from each patient was used as control group (alcohol fixation - total number: 24 smears). The remaining two smears were air-dried and rehydrated and were taken as the test group (test group A - rehydrated with aq. glycerine; total number: 24 smears, test group B - rehydrated with coconut oil; total number: 24 smears) for 5-10 minutes. Then, all 72 slides were stained by standard Papanicolaou stain. The slides were examined for cytomorphologic changes and a score was assigned from 0 to 3. Conclusion: Our study proved aq. glycerine to be a superior rehydrant in comparison to conventional wet fixed smears or coconut oil. Also, in studies where cytoplasmic evaluation is required, coconut oil can be used due to its superior quality.
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This document summarizes the relevant literature for the selection of preprocedural imaging in three clinical scenarios in patients needing endovascular treatment or cardioversion of atrial fibrillation. These clinical scenarios include preprocedural imaging prior to radiofrequency ablation; prior to left atrial appendage occlusion; and prior to cardioversion. The appropriateness of imaging modalities as they apply to each clinical scenario is rated as usually appropriate, may be appropriate, and usually not appropriate to assist the selection of the most appropriate imaging modality in the corresponding clinical scenarios. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
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Fibrilação Atrial , Medicina Baseada em Evidências , Sociedades Médicas , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Humanos , Estados Unidos , Cuidados Pré-Operatórios/métodos , Cardioversão Elétrica/métodos , Átrios do Coração/diagnóstico por imagem , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgiaRESUMO
In future generation networks, data protection is a crucial necessity particularly when information is sent on a system. Network protection has three objectives known as discretion, reliability and accessibility. The most common procedure exploited to attain this ambition is encryption. The Generalized Multi Protocol Label Switched (GMPLS) optical networks are designed to survive Internet Protocol's (IP's) unreliable delivery. In this paper, GMPLS network is proposed with random users and then the data protection algorithms have been analyzed on proposed GMPLS optical network. The various algorithms involve Rivest Shamir Adleman (RSA) algorithm and Advanced Encryption Standard (AES) algorithm. The considered algorithms are very popular but have not been implemented on GMPLS optical networks in the literature which shows the novelty of the presented work. The network performance is compared for these algorithms in terms of various parameters like blocking probability and latency. The results reveal that RSA reduces the blocking probability < 0.005 and latency < 0.007 ms. This shows that RSA gives better performance than AES algorithm and enhance the quality of service considering blocking probability, latency and overheads in GMPLS optical networks leading to enhanced data protection.
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In this study, Ferrites (Fe3O4, MnFe2O4, ZnFe2O4) and different stoichiometric ratios of ZnxMn1-xFe2O4 (x = 0.2, 0.4, 0.6, and 0.8) nanoparticles (<15 nm) were synthesized by microwave-assisted method and optimised for hyperthermia studies. The selection of the optimised variant of ferrite i.e. Zn0.4Mn0.6Fe2O4 was found to be the best variant based on VSM (38.14 emu g-1) hyperthermia-based temperature rise (maximum ΔT of 38 °C), SAR and ILP values. Trastuzumab, which is known to bind with HER2 receptors of breast cancer was chemically tethered onto Zn0.4Mn0.6Fe2O4 nanoparticles through EDC/NHS coupling with a loading efficiency of 80%. The attached Trastuzumab aided during the pre-treatment step by aiding in the internalisation of Zn0.4Mn0.6Fe2O4 nanoparticles, with cellular uptake of 11% in SK-BR-3 (cancerous HER2+) cells compared to â¼5% for MDA-MB-231 (cancerous HER2-) and RPE-1 (non-cancerous) cells. In the presence of a hyperthermia trigger for 15 mins, ZnxMn1-xFe2O4 -Trastuzumab formulation had a maximum therapeutic effect by reducing the SK-BR-3 cell viability to 14% without adversely affecting the RPE-1 cells. The mechanism of ZnxMn1-xFe2O4-Trastuzumab combination was examined using an internalisation study, MTT-based viability, proliferation study, and ROS generation assay. By utilizing both Trastuzumab and hyperthermia, we achieve their synergistic anticancer properties while minimizing the drug requirement and reducing any effect on non-cancerous cells.
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Neoplasias da Mama , Hipertermia Induzida , Nanopartículas , Humanos , Feminino , Trastuzumab/farmacologia , Trastuzumab/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Zinco , Linhagem Celular TumoralRESUMO
Recent studies have revealed the heterogeneous nature of astrocytes; however, how diverse constituents of astrocyte-lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We perform single-cell RNA sequencing of GFAP-expressing cells from sub-chronic spinal cord injury models and identify and compare with the subpopulations in acute-stage data. We find subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Immunohistochemistry, RNAscope experiments, and quantification by stereology verify the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before and after injury and uncover the populations of the intermediate cells enriched in neuronal genes that could potentially transition into other subpopulations. This study has expanded the knowledge of the heterogeneity and cell state transition of glial progenitors in adult spinal cord before and after injury.
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Neuroglia , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/genética , Astrócitos , Neurônios , Medula Espinal , Análise de Sequência de RNARESUMO
Estimating soil properties is important for maximizing the production of crops in sustainable agriculture. The hyperspectral data next input depends upon the previous one, and the current techniques do not take advantage of this sequential nature of hyperspectral signatures. The variants of RNN can learn the short-term and long-term dependencies between data. This paper proposes a deep learning hybrid framework for quantifying the soil minerals like Clay, CEC, pH of H2O, Nitrogen, Organic Carbon, Sand of European Union from the LUCAS library. The hyperspectral signatures contain the data in the range of 400-2500 nm captured from the FOSS spectroscope in the laboratory. As hyperspectral data is high dimensional, Principal Component Analysis and Locality Preserving Projections are utilized to form the hybrid features, which have low dimensions containing the local and global information of the original dataset. These hybrid features are passed on to Long Short Term Memory Networks, a deep learning framework for building an effective prediction model. The effectiveness of the prepared models is demonstrated by comparing it to existing state-of-the-art techniques.
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Redes Neurais de Computação , Solo , Agricultura , União Europeia , AreiaRESUMO
Massive efforts are being made to develop coronavirus disease 2019 (COVID-19) vaccines at an unprecedented rate. The vaccinations' adverse impact profile, on the other hand, has not been well established. Neurological complications are increasingly reported as a result of these vaccines. One such complication identified is immune-mediated inflammatory polyneuropathy, which affects peripheral nerves and neurons. We report a case of chronic inflammatory demyelinating polyneuropathy (CIDP) post-mRNA-1273 (Moderna) COVID-19 vaccine. Recognizing this complication and distinguishing it from Guillain-Barré syndrome enables timely initiation of treatment. Additionally, our report highlights a possible link between vaccination and subsequent development of CIDP, but conclusive evidence of a causal relationship requires more extensive studies.
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Hypertriglyceridemia is known to be the third most common etiology of acute pancreatitis. Triglyceride levels above 1,000 mg/dL are associated with an increased risk of acute pancreatitis. We present the case of a 22-year-old female, a known case of hypertriglyceridemia, who developed sudden onset severe epigastric abdominal pain. A marked elevation in triglyceride levels of >3,000 mg/dL, serum lipase levels of 722 U/L, and serum amylase levels of 161 U/L, in the absence of other risk factors of acute pancreatitis, suggested hypertriglyceridemia-induced acute pancreatitis. Computed tomography (CT) of the abdomen and pelvis with contrast confirmed acute pancreatitis with hepatic steatosis. She was initially placed nil per os (NPO) and intravenous (IV) fluids with normal saline were administered. However, she was subsequently transferred to the intensive care unit as she developed acute respiratory distress syndrome. She was started on IV insulin with 5% dextrose in normal saline and a hydromorphone hydrochloride patient-controlled analgesia (PCA) pump was used for pain control. The patient's condition improved gradually. At the time of discharge, the triglyceride (311 mg/dL) and lipase levels (81 U/L) of the patient were within the normal range. The prognosis of hypertriglyceridemia-induced acute pancreatitis is considered to be worse than non-hypertriglyceridemic acute pancreatitis. Patients with hypertriglyceridemia-induced acute pancreatitis need swift diagnosis and treatment to avoid serious complications.
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Anisotropic rare earth ion (RE3+) doped fluoride upconversion particles are emerging as potential candidate in diverse areas, ranging from biomedical imaging to photonics. Here, we develop a facile strategy to synthesize NaYF4: Yb, Gd, Er, and NaYF4: Yb, Gd, Tm upconversion nanorods via microwave synthesis route by controlling the synthesis time and compared the optical properties similar nanorods prepared via solvothermal technique. With the increase in synthesis time, the phase of the particle found to change from mixed phase to purely hexagonal and morphology of the particles change mixed phase of spherical and rod-shaped particles to completely nanorods for a synthesis time of 60 min. Further, the intrinsically hydrophobic particles changed to hydrophilic by removal of oleic capping via acid treatment and the amine functionalized silica coating. The upconversion luminescence as well as laser power dependent emission properties of the surface modified particles elucidate that surface modification route influence the upconversion luminescence as well as solvent dependent emission properties. Moreover, the laser power dependent studies elucidate that the upconversion process in a multi-photon process.
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Luminescência , Nanotubos , Fluoretos , Micro-Ondas , Nanotubos/química , Dióxido de SilícioRESUMO
Objective About 41 million people aged ≥18 years reported lifetime use of cocaine, and 5.4 million people reported having used cocaine in 2019. We aim to identify trends of cocaine use, manifestations, concomitant drug use, and financial burden on health care among hospitalized patients. Methods We utilized National Inpatient Sample from years 2006-2018. Patients with age ≥18 years, admitted to the hospital with a diagnosis of cocaine abuse, dependence, poisoning, or unspecified cocaine use were included in the study. We used ICD-9 Clinical Modification (CM) and ICD-10-CM codes to retrieve patient samples and comorbid conditions. The primary outcome was the trend in cocaine use among hospitalized patients from the year 2006 to 2018. Cochran-Mantel-Haenszel test was used to assess the significance of trends. Results In the year 2006, the prevalence of cocaine abuse among hospitalized patients was 10,751 per million with an initial decline to 7,451 per million in 2012 and a subsequent increase to 11,891 per million hospitalized patients in 2018 with p =0.01. The majority of patients admitted were older than 50 years (43.27%), and a greater percentage of patients were males. All ethnicities showed a rising trend in the use of cocaine except for Native Americans. Cardiovascular effects, neuropsychiatric and infectious manifestations in hospitalized patients with cocaine abuse showed a consistent increase from year 2006 to 2018 with p <0.001. Conclusions There is a recent uptrend in cocaine use among hospital admissions in the US from 2006 to 2018 with an increased rate of systemic manifestations. This highlights the impact of cocaine use on the health system and the dire need to address this growing problem.
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Glioblastoma (GBM) is a lethal brain cancer exhibiting high levels of drug resistance, a feature partially imparted by tumor cell stemness. Recent work shows that homozygous MTAP deletion, a genetic alteration occurring in about half of all GBMs, promotes stemness in GBM cells. Exploiting MTAP loss-conferred deficiency in purine salvage, we demonstrate that purine blockade via treatment with L-Alanosine (ALA), an inhibitor of de novo purine synthesis, attenuates stemness of MTAP-deficient GBM cells. This ALA-induced reduction in stemness is mediated in part by compromised mitochondrial function, highlighted by ALA-induced elimination of mitochondrial spare respiratory capacity. Notably, these effects of ALA are apparent even when the treatment was transient and with a low dose. Finally, in agreement with diminished stemness and compromised mitochondrial function, we show that ALA sensitizes GBM cells to temozolomide (TMZ) in vitro and in an orthotopic GBM model. Collectively, these results identify purine supply as an essential component in maintaining mitochondrial function in GBM cells and highlight a critical role of mitochondrial function in sustaining GBM stemness. We propose that purine synthesis inhibition can be beneficial in combination with the standard of care for MTAP-deficient GBMs, and that it may be feasible to achieve this benefit without inflicting major toxicity.
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ABSTRACT: Insulin-like growth factors have diverse functions in skeletal muscles by acting through multiple signaling pathways, including growth regulation and differentiation, anti-inflammation, and antioxidation. Insulin-like growth factors have anti-inflammatory effects and also play roles in nociceptive pathways, determining pain sensitivity, in addition to their protective role against ischemic injury in both the nervous system and skeletal muscle. In skeletal muscle, insulin-like growth factors maintain homeostasis, playing key roles in maintenance, accelerating muscle regeneration, and repair processes. As part of their maintenance role, increased levels of insulin-like growth factors may be required for the repair mechanisms after exercise. Although the role of insulin-like growth factors in myofascial pain syndrome is not completely understood, there is evidence from a recent study that insulin-like growth factor 2 levels in patients with myofascial pain syndrome are lower than those of healthy individuals and are associated with increased levels of inflammatory biomarkers. Importantly, higher insulin-like growth factor 2 levels are associated with increased pain severity in myofascial pain syndrome patients. This may suggest that too low or high insulin-like growth factor levels may contribute to musculoskeletal disorder process, whereas a midrange levels may optimize healing without contributing to pain hypersensitivity. Future studies are required to address the mechanisms of insulin-like growth factor 2 in myofascial pain syndrome and the optimal level as a therapeutic agent.
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Músculo Esquelético , Síndromes da Dor Miofascial , Humanos , Músculo Esquelético/fisiologia , DorRESUMO
Bevacizumab, a monoclonal immunoglobulin-G1 antibody directed against vascular endothelial growth factor (VEGF), inhibits angiogenesis. Gastrointestinal perforation is a serious and often fatal adverse event related to bevacizumab use. Bevacizumab is indicated in the treatment of colorectal malignancies, certain subtypes of non-small cell lung carcinoma, metastatic renal cell carcinomas, and cervical cancers. It is also indicated in the treatment of recurrent glioblastoma (GBM) in adult patients as the sole treatment agent or in combination with other antineoplastic medications. We present a case of a patient on bevacizumab currently with glioblastoma multiforme and seizures, who was previously treated with radiation treatment and temozolomide. The patient presented to the emergency room with abdominal pain, seizures and was diagnosed to have an intestinal perforation.
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Acute atraumatic carpal tunnel syndrome (CTS) that results from a hematoma as a complication of oral anticoagulation use is a highly uncommon presentation. CTS is a common type of peripheral compression neuropathy, with CTS's acute presentation being less common than chronic. The acute type is commonly caused either by recent trauma, including fractures of the distal radius and carpal dislocations, atraumatic etiologies like infections, or inflammatory conditions that increase the pressure in the carpal tunnel. Timely diagnosis of acute CTS is essential, as often surgical decompression is required if symptoms do not improve within hours. A 79-year-old female presented to the ED with a past medical history significant for stroke, paroxysmal atrial fibrillation on rivaroxaban, and hypertension. She complained of a one-day history of left wrist pain, swelling, and restricted range of motion, associated with numbness in the median nerve distribution and weakening of the handgrip. The patient denied any trauma or unusual physical activity. CCT imaging of the left upper extremity showed soft tissue expansion around the flexor pollicis longus proximal to and just distal to the carpal tunnel consistent with dissecting hematoma within the flexor compartment. The orthopedics hand team evaluated the patient. Her rivaroxaban was held, and she was monitored for 24 hours in the hospital. The next day, she almost had a complete resolution of her symptoms. She was discharged home with a close follow-up. There are various atraumatic causes of acute CTS. Spontaneous atraumatic hematoma occurring in the forearm's flexor compartment and resulting in acute CTS is extremely uncommon. In contrast to chronic CTS, acute CTS requires urgent carpal tunnel release to prevent irreversible median nerve damage. Anticoagulants in such cases increase the bleeding risk. This case highlights the importance of considering CTS into the differential diagnosis of someone on an anticoagulant and presenting with acute wrist swelling and pain. Despite the absence of any direct trauma, timely diagnosis of this condition is prudent and greatly affects the outcomes.
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Background: In microscopic assessment of mineralized tissue, decalcification is an important step during tissue processing. The present study was attempted to compare the efficacy of various decalcifying agents and to evaluate the most efficacious decalcifying agent. Aims and Objectives: The aim was to study and compare the time taken for complete decalcification of the specimen by six different chemical agents; to study and compare the effect of various decalcifying agents on cellular and nuclear changes of hard and soft tissues; to study and compare the effect of various decalcifying agents used on the staining intensity with Ehrlich's Hematoxylin and Eosin stain and to determine the ideal decalcification technique. Materials and Methods: The six decalcifying agents, namely 5% nitric acid, 8% formic acid, formalin-nitric acid, 5% trichloroacetic acid, neutral ethylenediaminetetraacetic acid (EDTA) and Perenyi's fluid were used to decalcify 30 human permanent teeth (5 teeth in each solution). The endpoint of decalcification was evaluated by chemical (calcium oxalate test) as well as radiographic methods. The specimens were then subjected to processing, sectioning and staining with hematoxylin and eosin. The stained sections were observed under a light microscope and grading was done. Results: The results in the present study confirmed the fact that the time required for complete decalcification process was least in Perenyi's fluid, 5% trichloroacetic acid and highest in 14% EDTA. Teeth decalcified in 5% trichloroacetic acid, 8% formic acid, formalin-nitric acid and 5% nitric acid were easy to section. Sectioning was most difficult for teeth decalcified in Perenyi's fluid and 14% EDTA. The overall structure details as well as staining characteristics were best in teeth decalcified by 5% trichloroacetic acid and neutral EDTA and worst in teeth decalcified by Perenyi's fluid. Conclusion: Five percent trichloroacetic acid was showing the most efficient result as it balances both tissue integrity and time factor suggesting that it can be used as a stable decalcifying agent for routine histopathological diagnosis.
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Strengthened DNA repair pathways in tumor cells contribute to the development of resistance to DNA-damaging agents. Consequently, targeting proteins in these pathways is a promising strategy for tumor chemosensitization. Here, we show that the expression of a subset of Fanconi anemia (FA) genes is attenuated in glioblastoma tumor cells deficient in methylthioadenosine phosphorylase (MTAP), a common genetic alteration in a variety of cancers. Subsequent experiments in cell line models of different cancer types illustrate that this reduced transcription of FA genes can be recapitulated by blockage of Protein Arginine Methyltransferase 5 (PRMT5), a promising therapeutically targetable epigenetic regulator whose enzymatic activity is compromised in MTAP-deficient cells. Further analyses provide evidence to support that PRMT5 can function as an epigenetic regulator that contributes to the increased expression of FA genes in cancer cells. Most notably and consistent with the essential roles of FA proteins in resolving DNA damage elicited by interstrand crosslinking (ICL) agents, PRMT5 blockage, as well as MTAP loss, sensitizes tumor cells to ICL agents both in vitro and in xenografts. Collectively, these findings reveal a novel epigenetic mechanism underlying the upregulated expression of FA genes in cancer cells and suggest that therapeutically targeting PRMT5 can have an additional benefit of chemosensitizing tumor cells to ICL agents. IMPLICATIONS: PRMT5 positively regulates the expression of FA genes. Inhibition of PRMT5 attenuates FA-dependent DNA repair pathway and sensitizes tumor cells to ICL agents.
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Epigênese Genética/genética , Anemia de Fanconi/genética , Expressão Gênica/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos , Camundongos NusRESUMO
In the United States, acute low back pain, with or without radiculopathy, is the leading cause of years lived with disability and the third ranking cause of disability-adjusted life-years. Uncomplicated acute low back pain and/or radiculopathy is a benign, self-limited condition that does not warrant any imaging studies. Imaging is considered in those patients who have had up to 6 weeks of medical management and physical therapy that resulted in little or no improvement in their back pain. It is also considered for those patients presenting with red flags, raising suspicion for a serious underlying condition, such as cauda equina syndrome, malignancy, fracture, or infection. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.