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Indole-3-acetic acid (IAA) is the most widely utilized plant growth regulator. Despite its extensive usage, IAA is often overlooked as an environmental pollutant. Due to its protein-binding nature, it also functions as a uremic toxin, contributing to its association with chronic kidney disease (CKD). While in vitro and epidemiological research have demonstrated this association, the precise impact of IAA on cardiovascular disease in animal models is unknown. The main objective of this study is to conduct a mechanistic analysis of the cardiotoxic effects caused by IAA using male Wistar albino rats as the experimental model. Three different concentrations of IAA (125, 250, 500 mg/kg) were administered for 28 days. The circulating IAA concentration mimicked previously observed levels in CKD patients. The administration of IAA led to a notable augmentation in heart size and heart-to-body weight ratio, indicating cardiac hypertrophy. Echocardiographic assessments supported these observations, revealing myocardial thickening. Biochemical and gene expression analyses further corroborated the cardiotoxic effects of IAA. Dyslipidemia, increased serum c-Troponin-I levels, decreased SOD and CAT levels, and elevated lipid peroxidation in cardiac tissue were identified. Moreover, increased expression of cardiac inflammatory biomarkers, including ANP, BNP, ß-MHC, Col-III, TNF-α, and NF-κB, was also found in the IAA-treated animals. Histopathological analysis confirmed the cardiotoxic nature of IAA, providing additional evidence of its adverse effects on cardiovascular health. These results offer insights into the potential negative impact of IAA on cardiovascular function, and elucidating the underlying mechanisms of its cardiotoxicity.
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Cardiomegalia , Ácidos Indolacéticos , Ratos Wistar , Animais , Masculino , Ratos , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Estresse Oxidativo/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologia , Biomarcadores/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , CardiotoxicidadeRESUMO
Cancer stands in the frontline among leading killers worldwide and the annual mortality rate is expected to reach 16.4 million by 2040. Humans suffer from about 200 different types of cancers and many of them have a small number of approved therapeutic agents. Moreover, several types of major cancers are diagnosed at advanced stages as a result of which the existing therapies have limited efficacy against them and contribute to a dismal prognosis. Therefore, it is essential to develop novel potent anticancer agents to counteract cancer-driven lethality. Natural sources such as bacteria, plants, fungi, and marine microorganisms have been serving as an inexhaustible source of anticancer agents. Notably, over 13,000 natural compounds endowed with different pharmacological properties have been isolated from different bacterial sources. In the present article, we have discussed about the importance of natural products, with special emphasis on bacterial metabolites for cancer therapy. Subsequently, we have comprehensively discussed the various sources, mechanisms of action, toxicity issues, and off-target effects of clinically used anticancer drugs (such as actinomycin D, bleomycin, carfilzomib, doxorubicin, ixabepilone, mitomycin C, pentostatin, rapalogs, and romidepsin) that have been derived from different bacteria. Furthermore, we have also discussed some of the major secondary metabolites (antimycins, chartreusin, elsamicins, geldanamycin, monensin, plicamycin, prodigiosin, rebeccamycin, salinomycin, and salinosporamide) that are currently in the clinical trials or which have demonstrated potent anticancer activity in preclinical models. Besides, we have elaborated on the application of metagenomics in drug discovery and briefly described about anticancer agents (bryostatin 1 and ET-743) identified through the metagenomics approach.
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Antineoplásicos , Produtos Biológicos , Neoplasias , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Fungos/metabolismo , BactériasRESUMO
Pseudomonas aeruginosa (PA) is an opportunistic pathogen that causes healthcare-associated infection and high mortality in immunocompromised patients. It produces several virulence factors through quorum sensing (QS) mechanisms that is essential for subverting host immune system. Even front-line antibiotics are unable to control PA pathogenicity due to the emergence of antibiotic resistance. Luteolin is a naturally derived compound that has proven to be the effective drug to annihilate pathogens through quorum quenching mechanism. In this study, the protective effect of luteolin against the PA-mediated inflammation was demonstrated using zebrafish model. Luteolin protects zebrafish from PA infection and increases their survival rate. It was found that PA-mediated ROS, lipid peroxidation, and apoptosis were also significantly reduced in luteolin-treated zebrafish larvae. Open field test (OFT) reveals that luteolin rescued PA-infected zebrafish from retarded swimming behavior. Furthermore, luteolin increases SOD and CAT levels and decreases LDH and NO levels in PA-infected zebrafish compare to control group. Histological and gene expression analysis reveals that luteolin protects PA-infected zebrafish by decreasing gut inflammation and altering the expression of inflammatory (TNF-α, IL-1ß, IL-6) and antioxidant markers (iNOS, SOD, CAT). Thus, luteolin was found to have dual effect in protecting PA-infected zebrafish by decreasing virulence factors production in PA and stimulating host immune system. This is the first study demonstrating the protective effect of luteolin using animal model. Hence, luteolin could be used as a future therapeutic drug to control multi-drug resistant PA.
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Infecções por Pseudomonas , Fatores de Virulência , Animais , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Pseudomonas aeruginosa , Luteolina/farmacologia , Peixe-Zebra , Percepção de Quorum , Inflamação , Superóxido Dismutase/metabolismo , Antibacterianos/metabolismo , Biofilmes , Proteínas de Bactérias/metabolismo , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/patologiaRESUMO
Diverse microbial communities colonize different habitats of the human body, including gut, oral cavity, nasal cavity and tissues. These microbial communities are known as human microbiome, plays a vital role in maintaining the health. However, changes in the composition and functions of human microbiome can result in chronic low-grade inflammation, which can damage the epithelial cells and allows pathogens and their toxic metabolites to translocate into other organs such as the liver, heart, and kidneys, causing metabolic inflammation. This dysbiosis of human microbiome has been directly linked to the onset of several non-communicable diseases. Recent metabolomics studies have revealed that pathogens produce several uraemic toxins. These metabolites can serve as inter-kingdom signals, entering the circulatory system and altering host metabolism, thereby aggravating a variety of diseases. Interestingly, Enterobacteriaceae, a critical member of Proteobacteria, has been commonly associated with several non-communicable diseases, and the abundance of this family has been positively correlated with uraemic toxin production. Hence, this review provides a comprehensive overview of Enterobacterial translocation and their metabolites role in non-communicable diseases. This understanding may lead to the identification of novel biomarkers for each metabolic disease as well as the development of novel therapeutic drugs.
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Microbioma Gastrointestinal , Microbiota , Doenças não Transmissíveis , Humanos , Enterobacteriaceae , Inflamação/microbiologiaRESUMO
Vermiform appendix is a highly variable organ, which is an enigma to the surgeon in terms of its position, size and symptoms. Attachment of its tip to the surrounding organs is relatively rare. Here we present a rare variation of vermiform appendix. The appendix was 12cm long and was in retrocecal and retrocolic position. Its tip was attached to the right lobe of the liver through a fibrous band which was 2cm long. This variation might pose difficulties in appendicular resection, renal and hepatic surgeries.
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Apendicite , Apêndice , Humanos , Apêndice/diagnóstico por imagem , Apendicite/diagnóstico , Apendicite/cirurgia , Fígado/diagnóstico por imagemRESUMO
Plastic recycling reduces the wastage of potentially useful materials as well as the consumption of virgin materials, thereby lowering the energy consumption, air pollution by incineration, soil and water pollution by landfilling. Plastics used in the biomedical sector have played a significant role. Reducing the transmission of the virus while protecting the human life in particular the frontline workers. Enormous volumes of plastics in biomedical waste have been observed during the outbreak of the pandemic COVID-19. This has resulted from the extensive use of personal protective equipment such as masks, gloves, face shields, bottles, sanitizers, gowns, and other medical plastics which has created challenges to the existing waste management system in the developing countries. The current review focuses on the biomedical waste and its classification, disinfection, and recycling technology of different types of plastics waste generated in the sector and their corresponding approaches toward end-of-life option and value addition. This review provides a broader overview of the process to reduce the volume of plastics from biomedical waste directly entering the landfill while providing a knowledge step toward the conversion of "waste" to "wealth." An average of 25% of the recyclable plastics are present in biomedical waste. All the processes discussed in this article accounts for cleaner techniques and a sustainable approach to the treatment of biomedical waste.
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We evaluated the cost-effectiveness of recurrent periods of 3 versus 6 years of zoledronic acid treatment prior to 3-year bisphosphonate holidays for US postmenopausal women with osteoporosis and femoral neck BMD T-scores between - 2.5 and - 3.5. We found that cycles of 3 years of treatment followed by holidays is likely to be the more cost-effective option. INTRODUCTION: We compared the effectiveness and cost-effectiveness of cycles of 3 years versus 6 years of zoledronic acid treatment prior to 3-year bisphosphonate holidays for US postmenopausal women with osteoporosis. METHODS: We developed an individual-level state-transition microsimulation cost-effectiveness model to compare treatment strategies over the lifetime of recurrent periods of 3 years of zoledronic acid followed by 3-year holidays (zoledronic acid 3/3), recurrent periods of 6 years of zoledronic acid followed by 3-year holidays (zoledronic acid 6/3), and no zoledronic acid treatment for women with osteoporosis and femoral neck BMD T-scores between - 2.5 and - 3.5. RESULTS: Base-case analysis and all key parameter sensitivity analysis findings for every treatment initiation age evaluated (50, 60, 70, and 80) revealed that zoledronic acid 3/3 was consistently the most cost-effective strategy, assuming a willingness-to-pay of $100,000 per quality-adjusted life-year (QALY). In general, the zoledronic acid 3/3 and 6/3 strategies were relatively close in effectiveness (QALYs) over the lifetime; however, lifetime direct health care costs were on average approximately $2000 lower for the 3/3 strategy. Probabilistic sensitivity analysis results revealed that the zoledronic acid 3/3 strategy was favored in greater than 70% of the iterations for a willingness-to-pay threshold of $100,000/QALY for all treatment initiation ages evaluated. CONCLUSIONS: After 3 years of zoledronic acid treatment for postmenopausal women with osteoporosis and femoral neck BMD T-scores between - 2.5 and - 3.5, taking 3-year holidays before restarting another treatment cycle is likely to be more cost-effective over the lifetime than cycles of 6 years of treatment prior to 3-year holidays.
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Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Conservadores da Densidade Óssea/uso terapêutico , Análise Custo-Benefício , Difosfonatos/uso terapêutico , Feminino , Férias e Feriados , Humanos , Osteoporose/tratamento farmacológico , Osteoporose Pós-Menopausa/tratamento farmacológico , Anos de Vida Ajustados por Qualidade de Vida , Ácido ZoledrônicoRESUMO
Mangroves play a key role in ecosystem balancing and climate change mitigation. It acts as a source and sink of methane (CH4), a major greenhouse gas responsible for climate change. Energy metabolic pathways of methane production (methanogenesis) and oxidation (methanotrophy) are directly driven by sulphur (S) and nitrogen (N) metabolism and salinity in coastal wetlands. To investigate, how mangrove-degradations, affect the source-sink behaviour of CH4; the pathways of CH4, S and N were studied through whole-genome metagenomic approach. Soil samples were collected from degraded and undisturbed mangrove systems in Sundarban, India. Structural and functional microbial diversities (KEGG pathways) of CH4, S and N metabolism were analysed and correlated with labile carbon pools and physico-chemical properties of soil. Overall, the acetoclastic pathway of methanogenesis was dominant. However, the relative proportion of conversion of CO2 to CH4 was more in degraded mangroves. Methane oxidation was higher in undisturbed mangroves and the serine pathway was dominant. After serine, the ribulose monophosphate pathway of CH4 oxidation was dominant in degraded mangrove, while the xylulose monophosphate pathway was dominant in undisturbed site as it is more tolerant to salinity and higher pH. The assimilatory pathway (AMP) of S-metabolism was dominant in both systems. But in AMP pathway, adenosine triphosphate sulfurylase enzyme reads were higher in degraded mangrove, while NADPH-sulfite reductase abundance was higher in undisturbed mangrove due to higher salinity, and pH. In N-metabolism, the denitrification pathway was predominant in degraded sites, whereas the dissimilatory nitrate reduction pathway was dominant in undisturbed mangroves. The relative ratios of sulphur reducing bacteria (SRB): methanogens were higher in degraded mangrove; however, methanotrophs:methanogens was higher in undisturbed mangrove indicated lower source and greater sink capacity of CH4 in the system. Microbial manipulation in mangrove-rhizosphere for regulating major energy metabolic pathways of methane could open-up a new window of climate change mitigation in coastal wetlands.
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Ecossistema , Metano , Dióxido de Carbono/análise , Mudança Climática , Redes e Vias Metabólicas , Nitrogênio , Solo , Enxofre , Áreas AlagadasRESUMO
The scrotum is supplied by ilioinguinal, genital branch of genitofemoral, perineal branch of the posterior cutaneous nerve of the thigh and the posterior scrotal branches of the pudendal nerve. We report an extremely rare innervation of the anterior part of the scrotum by the anterior division of the right obturator nerve. The genital branch of genitofemoral nerve did not reach the scrotum. The ilioinguinal nerve did not supply the scrotum. The anterior division of the obturator nerve gave a branch which ascended superomedially in the thigh, crossed superficial to the spermatic cord and communicated with the right ilioinguinal nerve. As it crossed the spermatic cord, it gave a scrotal branch which descended over the spermatic cord and ramified to supply the anterior part of the scrotum. Knowledge of this variation could be important to anaesthesiologists, urologists and surgeons in general.
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Nervo Obturador , Escroto , Humanos , Plexo Lombossacral , Masculino , Escroto/inervação , Escroto/cirurgiaRESUMO
Flexor digitorum accessorius (quadratus plantae) is a muscle of second layer of the sole of the foot. Though it is not a very important muscle in terms of movements or stability of foot, it could pose problems when it presents variations. We observed a novel, accessory slip of flexor digitorum accessorius. The slip arose from the fascia covering abductor digiti minimi muscle and got inserted into the tendon of the flexor digitorum longus muscle. It was supplied by a branch from lateral plantar nerve. The proximal part of this accessory slip surrounded the lateral plantar nerve and vessels. Compression of lateral plantar nerve by this accessory slip might produce symptoms similar to that of tarsal tunnel syndrome and lead to misdiagnosis. The case could be of importance to foot and ankle surgeons and radiologists.
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Músculo Esquelético , Tendões , PéRESUMO
Common iliac vein variations are relatively rare compared to the variations of external and internal iliac veins. A rare pattern of formation of common iliac vein by the confluence of four veins is being reported here. The left common iliac vein was formed by the union of left external iliac vein, internal iliac vein, iliolumbar vein and a common trunk formed by the obturator and vesical veins. External iliac vein and obturator veins were connected by a communicating vein. Both external and common iliac veins were respectively medial to the external and common iliac arteries. Knowledge of this variant formation of common iliac vein could be useful to radiologists, gynecologists and orthopedic surgeons.
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Veia Ilíaca , Pelve , Abdome , Aorta Abdominal , Artéria Ilíaca/diagnóstico por imagem , Veia Ilíaca/diagnóstico por imagemRESUMO
Jejunum is drained into superior mesenteric vein through a series of jejunal veins. The way in which the first jejunal vein terminates is of great importance in upper abdominal surgery and radiological procedures. Knowledge of its variations is particularly important in surgical procedures like orthotropic hepatic transplantation, hepatic vein reconstruction, pancreatic surgery and surgical procedures of duodenojejunal junction. We saw a first jejunal vein opening directly into the portal vein. Further, the inferior mesenteric vein drained into the first jejunal vein. This case could be useful to gastroenterologists, general surgeons and radiologists.
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Veias Mesentéricas , Veia Porta , Abdome , Veias Mesentéricas/diagnóstico por imagem , Veias Mesentéricas/cirurgia , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgiaRESUMO
Gall bladder is known for many congenital anomalies such as duplication, intrahepatic position, floating position etc. Most of its anomalies can be detected in ultrasound examination and radiography. We report an extremely rare congenital anomaly of gall bladder as observed in a male cadaver during dissection classes. The gall bladder was totally enclosed in the right free margin of the lesser omentum, in front of the usual contents of the right free margin of lesser omentum. The size, shape and blood supply of the gall bladder were normal. Though this anomaly might not cause any functional disturbances, it might result in complications during laparoscopic cholecystectomy.
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Colecistectomia Laparoscópica , Vesícula Biliar , Vesícula Biliar/anormalidades , Vesícula Biliar/diagnóstico por imagem , Humanos , Fígado , Masculino , Mesentério , Omento/diagnóstico por imagemRESUMO
Signal transducer and activator of transcription 3 (STAT3) is a tumorigenic transcription factor that is persistently activated in various human cancers including hepatocellular carcinoma (HCC). Therefore, STAT3 is considered as a prominent target to counteract the uncontrolled proliferation of cancer cells. In the present report, pyrimidine-2,4-diones (N-methyluracil derivatives) (MNK1-MNK14) were synthesized in an ionic liquid (BMIm PF6) medium employing a ligand-free Suzuki-Miyaura cross-coupling process. Among the 14 derivatives, compound MNK8 showed good cytotoxicity towards both the tested cell lines and did not display a toxic effect against normal hepatocytes (LO2). MNK8 significantly increased the Sub-G1 cell count in both cell lines and the cytotoxic effect of MNK8 was found to be mediated through the suppression of constitutive phosphorylation of STAT3Y705. It also decreased the DNA interaction ability of nuclear STAT3 in HCC cells. MNK8 downregulated the levels of apoptosis-related proteins (such as Bcl-2, cyclin D1, survivin) and increased cleaved caspase-3 inferring the apoptogenic effect of MNK8. It also reduced the CXCL12-triggered cell migration and invasion in in vitro assay systems. Overall, MNK8 has been demonstrated as a new inhibitor of STAT3 signaling cascade in HCC cells.
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Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fator de Transcrição STAT3/genética , Transdução de SinaisRESUMO
We performed a cost-effectiveness analysis comparing 5 versus 10 years of alendronate treatment prior to 5-year drug holiday for US postmenopausal women with hip BMD T-scores between - 2.5 and - 3.5. We found that for most postmenopausal women 5 years of treatment prior to drug holiday is the more effective and cost-effective option. INTRODUCTION: We performed a cost-effectiveness analysis to compare 5 versus 10 years of alendronate treatment prior to 5-year drug holiday for postmenopausal osteoporotic women. METHODS: We created an individual-level state-transition microsimulation model to compare 3 treatment strategies for US postmenopausal women with osteoporosis and femoral neck BMD T-scores between - 2.5 and - 3.5 at baseline: recurrent periods of 5 years of alendronate followed by 5 years of drug holiday (alendronate 5/5), recurrent periods of 10 years of alendronate followed by 5 years of drug holiday (alendronate 10/5), and no alendronate treatment. RESULTS: Base-case analysis revealed for women initiating treatment at ages 50, 60, and 70, the alendronate 5/5 strategy dominated (was more effective and less costly than) the alendronate 10/5 strategy and no treatment. For women age 80, the alendronate 10/5 strategy dominated. When assuming a lower relative risk of nonvertebral fracture during years 6-10 of alendronate treatment than the base-case assumption, the alendronate 10/5 strategy became the most cost-effective strategy even at younger treatment initiation ages. Probabilistic sensitivity analysis results supported the base-case findings; for treatment initiation ages of 50, 60, and 70, the alendronate 5/5 strategy was favored, whereas for treatment initiation age of 80, the alendronate 10/5 strategy was favored; however, there was uncertainty in these findings. CONCLUSIONS: After 5 years of alendronate treatment, younger postmenopausal women (ages 50-70) with osteoporosis would likely benefit from a drug holiday, whereas older women (age 80) are likely to benefit from treatment for 10 years before a drug holiday.
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Alendronato/uso terapêutico , Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Preparações Farmacêuticas , Idoso , Idoso de 80 Anos ou mais , Alendronato/economia , Conservadores da Densidade Óssea/economia , Conservadores da Densidade Óssea/uso terapêutico , Análise Custo-Benefício , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Cooling of beams of gold ions using electron bunches accelerated with radio-frequency systems was recently experimentally demonstrated in the Relativistic Heavy Ion Collider at Brookhaven National Laboratory. Such an approach is new and opens the possibility of using this technique at higher energies than possible with electrostatic acceleration of electron beams. The challenges of this approach include generation of electron beams suitable for cooling, delivery of electron bunches of the required quality to the cooling sections without degradation of beam angular divergence and energy spread, achieving the required small angles between electron and ion trajectories in the cooling sections, precise velocity matching between the two beams, high-current operation of the electron accelerator, as well as several physics effects related to bunched-beam cooling. Here we report on the first demonstration of cooling hadron beams using this new approach.
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Epoxy-polydimethylsiloxane-graphene oxide (EPG) nanocomposite coatings were successfully developed by loading different wt% of graphene oxide nanosheets (GNs) into an epoxy-hydroxy-terminated-polydimethylsiloxane (EP-hPD) matrix via a facile in situ preparation technique. The inclusion of GNs into EPN led to an increase in modulus of elasticity and tensile strength up to 1570.46 MPa and 31.54 MPa, respectively, in the case of 1 wt% loading of GNs in the EP-hPD matrix. Also, an increase in the water contact angle from 90.1° to 115.2°, 104.5° and 101.7° was discerned at 1, 3 and 5 wt% loadings of GNs respectively. Taber abrasion results demonstrated a decrease in abrasion loss by 33.3% at 1 wt% loading of GNs in comparison to the unreinforced coating. An improvement in the glass transition temperature (Tg) was observed from 63.5 °C for the neat sample to 77.6 °C, 76.3 °C and 71.6 °C for the 1, 3 and 5 wt% EPG nanocomposites, respectively. An inevitable enhancement in the properties of the nanocomposites was affirmed due to the synergistic effect of GNs dispersed within the EP-hPD blend matrix. The prominent findings of this work include a minimum corrosion rate of 0.73 × 10-2 mm per year and upgradation in the antifouling performance of the nanocomposite coatings in comparison to the neat coating.
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AIM: To develop a robust toolkit to aid decision-making for mechanical thrombectomy (MT) based on readily available patient variables that could accurately predict functional outcome following MT. MATERIALS AND METHODS: Data from patients with anterior circulation stroke who underwent MT between October 2009 and January 2018 (n=239) were identified from our MT database. Patient explanatory variables were age, sex, National Institutes of Health Stroke Scale (NIHSS), Alberta Stroke Program Early CT Score (ASPECTS), collateral score, and Glasgow Coma Scale. Five models were developed from the data to predict five outcomes of interest: model 1: prediction of survival: modified Rankin Scale (mRS) of 0-5 (alive) or 6 (dead); model 2: prediction of good/poor outcome: mRS of 0-3 (good), or 4-6 (poor); model 3: prediction of good/poor outcome: mRS of 0-2 (good), or 3-6 (poor); model 4: prediction of mRS category: mRS of 0-2 (no disability), 3 (minor disability), 4-5 (severe disability) or 6 (dead); model 5: prediction of the exact mRs score (mRs as a continuous variable). The accuracy and discriminative power of each predictive model were tested. RESULTS: Prediction of survival was 87% accurate (area under the curve [AUC] 0.89). Prediction of good/poor outcome was 91% accurate (AUC 0.94) for Model 2 and 95% accurate (AUC 0.98) for Model 3. Prediction of mRS category was 76% accurate, and increased to 98% using the "one-score-out rule". Prediction of the exact mRS value was accurate to an error of 0.89. CONCLUSIONS: This novel toolkit provided accurate estimations of outcome for MT.
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Angiografia Cerebral , Angiografia por Tomografia Computadorizada , Técnicas de Apoio para a Decisão , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Idoso , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise de Sobrevida , Trombectomia/mortalidadeRESUMO
We performed a systematic review on the effect of drug holidays (discontinuation) on bone mineral density (BMD) and fracture risk. Bisphosphonate discontinuation may be considered for women who do not have low hip BMD after 3-5 years of initial treatment, while women who have low hip BMD may benefit from treatment continuation. INTRODUCTION: We performed a systematic review and meta-analysis on the effect of drug holidays (discontinuation) on BMD and fracture risk. METHODS: We searched PubMed, Embase, and Cochrane Library databases to locate controlled clinical trials and cohort studies evaluating the effect of drug holidays/discontinuation versus osteoporosis treatment continuation. We performed random-effects meta-analyses of hazard ratios of hip and any clinical osteoporotic fracture for individuals who discontinued bisphosphonates compared to persistent users. RESULTS: Thirteen records reporting results from eight different studies met inclusion criteria. The FLEX study found a reduced clinical vertebral fracture risk with 10 years of alendronate therapy compared to 5 (RR 0.45, 95% CI 0.24-0.85), and the HORIZON extension studies found a reduced risk of morphometric vertebral fracture with 6 years of zoledronic acid therapy compared to 3 (OR = 0.51, 95% CI 0.26-0.95); subgroup analyses showed that women with low hip BMD T-scores after the initial treatment period benefitted from continued treatment in terms of reduced vertebral fracture risk. Meta-analysis of adjusted hazard ratios of hip and any clinical osteoporotic fracture for women who discontinued bisphosphonates revealed no significant differences in the risk of hip fracture (summary estimate of HR 1.09, 95% CI 0.87-1.37) or any clinical fracture (summary estimate of HR 1.13, 95% CI 0.75-1.70) compared to persistent users. CONCLUSIONS: Bisphosphonate discontinuation may be considered for women who do not have low hip BMD after 3 to 5 years of initial treatment, while women who have low hip BMD may benefit from treatment continuation.
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Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Tomada de Decisão Clínica/métodos , Difosfonatos/farmacologia , Difosfonatos/uso terapêutico , Esquema de Medicação , Humanos , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/fisiopatologia , Medição de Risco/métodos , Suspensão de TratamentoRESUMO
Extreme complexity in the range of metallic and non-metallic parts present in waste printed circuit boards leads to incineration for collecting valuable metals. The non-metallic parts of the printed circuit board can be used effectively without affecting the environment. In this study, the non-metallic parts of the printed circuit board, which is made up by cross-linked resin and fibre, was used as a filler in recycled plasticised polyvinyl chloride collected from waste wires and cables. The properties of the plasticised polyvinyl chloride matrix and plasticised polyvinyl chloride-non-metallic parts of printed circuit board composite were compared with each other by means of mechanical properties and thermal properties. Both mechanical and thermal properties results indicated that incorporation of non-metallic parts of printed circuit board significantly improved the hardness, stiffness, abrasion resistance and thermal stability of plasticised polyvinyl chloride-non-metallic parts of printed circuit board composite; however, the tensile strength of the composite material is not improved because of poor adhesion between the plasticised polyvinyl chloride matrix and non-metallic parts of printed circuit board filler. The poor chemical interaction is also observed from Fourier transform infrared spectroscopy results. This plasticised polyvinyl chloride-non-metallic parts of printed circuit board composite can reduce the leaching of a hazardous element from the printed circuit board with effective utilisation of plastics fraction from waste wires and cables.