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INTRODUCTION: According to the American Academy of Sleep Medicine, obstructive sleep apnoea (OSA) is sleep-related breathing disorder that involves a decrease or complete halt in airflow despite an ongoing effort to breathe. The OSA-18 questionnaire is a short and self-administered questionnaire to assess paediatric patients' symptoms and quality of life with obstructive sleep apnoea. MATERIALS AND METHODS: This cross-sectional study is conducted at the Otorhinolaryngology-Head and Neck Surgery (ORL-HNS) clinic of Hospital Universiti Sains Malaysia. The forward and backward translation of the OSA- 18 questionnaire into the Malay language (Malay OSA-18) was performed and tested for content and face validity. The questionnaire's internal validity and reliability were tested using Pearson's correlation, Cronbach α and inter-reliability coefficient tests. The psychometric properties (validity, reliability and reproducibility) were assessed. RESULTS: We observed 84 patients ranging from six months up to 12 years of age. The mean age was 8 years old, and 63.1% were male patients. Among the samples, 96.4% presented with palatine tonsillar enlargement, and 84.5% presented with adenoid tonsillar enlargement. Based on the questionnaire the patient's caregiver answered, Pearson's correlation demonstrated that all the symptom scales correlate and measure the same things. The Cronbach's α coefficient value for each symptom scale was acceptable, within 0.6-0.8. The total Cronbach's α coefficient value was 0.89. The test-retest evaluation was excellent, with the value of intraclass correlation (ICC) more than 0.90. CONCLUSION: The Malay version of the OSA-18 questionnaire is equivalent to the original English version. It is an effective tool to assess the paediatric OSA patient's symptoms and quality of life based on the obtained validity, reliability and reproducibility values. Therefore, it is recommended to be a screening tool in daily practice.
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Qualidade de Vida , Apneia Obstrutiva do Sono , Traduções , Humanos , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Masculino , Malásia , Criança , Feminino , Estudos Transversais , Inquéritos e Questionários , Pré-Escolar , Reprodutibilidade dos Testes , Lactente , PsicometriaRESUMO
BACKGROUND: Cardiac magnetic resonance imaging (CMR) is the modality of choice for quantification of myocardial iron overload in ß-thalassemia major patients using the T2* sequence. CMR feature tracking (FT) is a recent magnetic resonance imaging tool that gives an idea about myocardial fibers deformation; thus, it can detect early impairment in myocardial function even before the reduction in ejection fraction. METHODS: This study aims to assess the ability of left ventricular CMR-FT in the early detection of systolic dysfunction in ß thalassemia major patients and to correlate it with the degree of myocardial iron overload measured by CMR T2*. This prospective study enrolled 57 ß thalassemia major patients who received long-term blood transfusion and 20 healthy controls. CMR was used to evaluate left ventricular volumes, ejection fraction, and the amount of myocardial T2*. A two-dimensional left ventricular FT analysis was performed. Both global and segmental left ventricular strain values were obtained. RESULTS: The mean global circumferential strain (GCS) and global radial strain (GRS) values were significantly lower in patients compared to control (P = 0.002 and P = 0.006, respectively). No correlation was found between T2* values and ejection fraction; however, there was a significant correlation between T2* values and GCS and GRS (P = 0.012 and P = 0.025, respectively) in thalassemia patients. Regional strain revealed significantly lower values of GCS and GRS in basal regions compared to apical ones (P = 0.000). CONCLUSIONS: Our study revealed that CMR-FT can play a role in the early detection of systolic impairment in thalassemia patients.
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This research was undertaken to assess the effect of tragacanth gum-chitin nanofiber (TG-CNF) film containing free (CEO) or encapsulated cumin essential oil (CNE) combined with oxygen absorber (OA) packaging on the shelf-life of ready-to-cook (RTC) turkey breast burgers during chilled storage. The experimental groups were OA and TG-CNF as single treatments, TG-CNF + CEO, TG-CNF + CNE, and TG-CNF + OA as binary treatments, TG-CNF + CEO + OA and TG-CNF + CNE + OA as ternary treatments, and control. The samples were stored at 3°C for 20 days and analyzed for microbial, physicochemical, and sensory attributes. Binary treatments, when compared to single treatments, and ternary treatments, when compared to binary treatments, exhibited enhanced effectiveness in managing microbial growth, hindering physicochemical alterations, and decelerating sensory alterations. At day 20, TG-CNF + CNE + OA group was identified as the most effective group in inhibiting the growth of total mesophilic bacteria (TMB), total psychrophilic bacteria (TSB), and coliforms (final counts were 4.8, 4.16, and ≤1 log CFU/g, respectively), and TG-CNF + CNE + OA and TG-CNF + CEO + OA groups were known as the most effective groups in inhibiting lactic acid bacteria (LAB) (final counts were 4.71 and 5.15 log CFU/g, respectively). Furthermore, the TG-CNF + CNE + OA treatment proved to be the most effective group in reducing the total volatile nitrogen (TVN) (final level was 19.2 mg N/100 g) and thiobarbituric acid reactive substances (TBARS) (final level was 0.119 mg malondialdehyde (MDA)/kg). TG-CNF + CNE + OA and TG-CNF + CEO + OA were the most efficient groups to delay the increasing rate of cooking loss (final values were 23.3% and 24.6%) and pH (final values were 7.01 and 6.99). The sample's shelf-life was 4 days in control and TG-CNF, 8 days in OA and TG-CNF + OA, 12 days in TG-CNF + CEO, 16 days in TG-CNF + CNE and TG-CNF + CEO + OA, and at least 20 days in TG-CNF + CNE + OA. As a result, the incorporation of TG-CNF + CNE alongside OA packaging emerges as a highly effective active packaging method for preserving RTC turkey breast burgers during chilled storage.
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OBJECTIVE: Colorectal cancer, one of the most frequently diagnosed cancers worldwide, has a high mortality rate. Thus, our research aims to examine the preventive effects of diosmin (DIO) alone and in conjunction with the anti-cancer drug irinotecan (camptothecin-11, CPT-11), on 1,2-dimethylhydrazine (DMH)-induced colon cancer (CC) in male Wistar rats. MATERIALS AND METHODS: Fifty adult male Wistar rats were categorized into five groups. Group I (Normal) received saline 0.9 orally % as a vehicle once a week for 14 weeks. Group II (DMH) received DMH (20 mg/kg/week) orally dissolved in 0.9% saline for 14 weeks and 1% carboxymethylcellulose (CMC) every other day for the final 10 weeks. Group III (DMH+DIO) received DMH orally for 14 weeks and DIO (10 mg/kg, suspended in 1% CMC) every other day for the final 10 weeks. Group IV (DMH+CPT-11) received DMH orally for 14 weeks and intraperitoneal injection of CPT-11 (3 mg/kg) twice a week for the final 10 weeks. Group V (DMH+DIO+CPT-11) orally received DMH for 14 weeks and both DIO and CPT-11. RESULTS: All treated groups showed a significant reduction (p<0.05) in their elevated serum malondialdehyde levels and significant amelioration (p<0.05) of their lowered activities of colon glutathione-S-transferase (GST) and glutathione reductase (GR) as well as serum glutathione level (GSH). In addition, simultaneous treatment with DIO and CPT-11 led to a significant decrease (p<0.05) in the elevated serum levels of carcinoembryonic antigen (CEA) in rats administered with DMH, as well as a reduction in the colon expression levels of the inflammatory mediator (NF-κB), cell proliferator protein (Ki-67), and proapoptotic protein (p53). CONCLUSIONS: These findings suggest DIO, CPT-11, and their combination have anticarcinogenic effects against DMH-induced CC by suppressing oxidative stress, simulating the antioxidant defense system, attenuating the inflammatory effects, and reducing cell proliferation.
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1,2-Dimetilidrazina , Neoplasias do Colo , Diosmina , Irinotecano , Ratos Wistar , Animais , Masculino , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/prevenção & controle , Neoplasias do Colo/metabolismo , Ratos , Diosmina/farmacologia , Diosmina/administração & dosagem , Irinotecano/farmacologia , Irinotecano/administração & dosagem , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
Alzheimer's disease (AD) is a neurodegenerative disease that badly impacts patients and their caregivers. AD is characterized by deposition of amyloid beta (Aß) and phosphorylated tau protein (pTau) in the brain with underlying neuroinflammation. We aimed to develop a neuroprotective paradigm by loading verapamil (VRH) into hyaluronic acid-modified carbon quantum dots (CQDs) and comparing its effectiveness with the free form in an AD-like model in rats induced by lipopolysaccharide (LPS). The experimental rats were divided into seven groups: control, LPS, CQDs, early free VRH (FVRH), late FVRH, early verapamil carbon quantum dots (VCQDs), and late VCQDs. Characterizations of VCQDs, the behavioral performance of the rats, histopathological and immunohistochemical changes, some AD hallmarks, oxidative stress biomarkers, neuro-affecting genes, and DNA fragmentation were determined. VRH was successfully loaded into CQDs, which was confirmed by the measured parameters. VRH showed enhancement in cognitive functions, disruption to the architecture of the brain, decreased Aß and pTau, increased antioxidant capacity, modifiable expression of genes, and a decline in DNA fragmentation. The loaded therapy was superior to the free drug. Moreover, the early intervention was better than the late, confirming the implication of the detected molecular targets in the development of AD. VRH showed multifaceted mechanisms in combating LPS-induced neurotoxicity through its anti-inflammatory and antioxidant properties, thereby mitigating the hallmarks of AD. Additionally, the synthesized nanosystem approach exhibited superior neuroprotection owing to the advantages offered by CQDs. However, finding new actionable biomarkers and molecular targets is of decisive importance to improve the outcomes for patients with AD.
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Carbono , Lipopolissacarídeos , Fármacos Neuroprotetores , Pontos Quânticos , Verapamil , Animais , Pontos Quânticos/química , Lipopolissacarídeos/efeitos adversos , Ratos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Verapamil/farmacologia , Carbono/química , Masculino , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas tau/metabolismo , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/metabolismoRESUMO
Proper utilization of agricultural land is a big challenge as they often laid over as waste lands. Farming is a significant occupation in any country and improving it further by promoting more farming opportunities will take the country towards making a huge leap forward. The issue in achieving this would be the lack of knowledge of cultivable land for food crops. The objective of this work is to utilize modern computer vision technology to identify and map cultivable land for agricultural needs. With increasing population and demand for food, improving the farming sector is crucial. However, the challenge lies in the lack of suitable land for food crops cultivation. To tackle this issue, we propose to use sophisticated image processing techniques on satellite images of the land to determine the regions that are capable of growing food crops. The solution architecture includes enhancement of satellite imagery using sophisticated pan sharpening techniques, notably the Brovey transformation, aiming to transform dull satellite images into sharper versions, thereby improving the overall quality and interpretability of the visual data. Making use of the weather data on the location observed and taking into factors like the soil moisture, weather, humidity, wind, sunlight times and so on, this data is fed into a generative pre-trained transformer model which makes use of it and gives a set of crops that are suitable to be grown on this piece of land under the said conditions. The results obtained by the proposed fusion approach is compared with the dataset provided by the government for different states in India and the performance was measured. We achieved an accuracy of 80% considering the crop suggested by our model and the predominant crop of the region. Also, the classification report detailing the performance of the proposed model is presented.
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This study aimed to assess the effect of coating based on nanochitosan-whey protein isolate (NCH-WPI) containing summer savory essential oil (SEO) combined with oxygen absorber (OA) packaging on Pseudomonas aeruginosa, Listeria monocytogenes, and Escherichia coli O157H7, inoculated to rainbow trout fillets stored under refrigeration. Except control and OA groups, L. monocytogenes decreased (0.49-1.82 log CFU/g) in all treatment groups until the eighth day, and then increased (0.39-0.68 log CFU/g). This indicates that the treatments were ineffective to inhibit the proliferation of this bacterium. Considering the forced aerobic nature of inoculated P. aeruginosa, the counts of these bacteria become undetectable in groups packed with OA after the fourth day of storage, while the other groups showed an increase (0.99-2.23 log CFU/g) in this bacteria population during entire storage period. This growth rate was slower in the NCH-WPI + 1%SEO and NCH-WPI + 2%SEO groups. Regarding the inoculated E. coli, its count was decreased (1.48-2.41 log CFU/g) during storage, and this reduction (2.24-2.41 log CFU/g) was the highest in NCH-WPI + 1%SEO + OA and NCH-WPI + 2%SEO + OA groups. In conclusion, NCH-WPI treatments delayed the growth of all pathogenic bacteria, but the ternary treatment (NCH-WPI + SEO + OA) was the most effective treatment in this regard.
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Over the last decade, randomized clinical trials of several pharmacologic agents have demonstrated a reduction in cardiovascular mortality and other important secondary outcomes. Angiotensin-Neprilysin Inhibitors and Sodium-Glucose Co-transporter 2 inhibitors have now become pillars in the treatment of heart failure. Ivabradine is a negative chronotropic agent used as an adjunctive therapy in patients with heart failure. Two new hypertension therapies, zilebresiran and aprocitentan, are currently in investigational stages. Finally, mavacamten has emerged as a pharmacologic treatment for hypertrophic obstructive cardiomyopathy. Practitioners must be familiar with the indications and side effects of newer therapies as they are now frequently prescribed.
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Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Ivabradina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Valsartana , Ácidos Dicarboxílicos , Ácidos Graxos , RNA Interferente PequenoRESUMO
This study aims to investigate the molecular mechanisms and the neuroprotective effect of hyaluronic acid modified verapamil-loaded carbon quantum dots (VRH-loaded HA-CQDs) against an in-vitro Alzheimer's disease model induced by amyloid beta (Aß) in SH-SY5Y and Neuro 2a neuroblastoma cells. Briefly, different HA-CQDs were prepared using hydrothermal method and optimized by Box-Behnken design to maximize quantum yield and minimize particle size. Serum stable negatively charged VRH-loaded HA-CQDs was successfully prepared by admixing the optimized HA-CQDs and VRH with association efficiency and loading capacity of 81.25 ± 3.65 % and 5.11 ± 0.81 %, respectively. Cells were pretreated with VRH solution or loaded-HA-CQDs followed by exposure to Aß. Compared to the control group, amyloidosis led to reduction in cellular proliferation, mitochondrial membrane potential, expression of cytochrome P450, cytochrome c oxidase, CREB-regulated transcriptional coactivator 3, and mitotic index, along with marked increase in reactive oxygen species (ROS) and inflammatory cytokines. Pretreatment with VRH, either free or loaded HA-CQDs, enhanced cell survival, mitochondrial membrane potential, mitotic index, and gene expression. It also reduced inflammation and ROS. However, VRH-loaded HA-CQDs exhibited superior effectiveness in the measured parameters. These findings suggest that VRH-loaded HA-CQDs have enhanced therapeutic potential compared to free VRH in mitigating amyloidosis negative features.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Carbono , Ácido Hialurônico , Fármacos Neuroprotetores , Pontos Quânticos , Espécies Reativas de Oxigênio , Verapamil , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Pontos Quânticos/química , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Humanos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Carbono/química , Carbono/farmacologia , Verapamil/farmacologia , Peptídeos beta-Amiloides/metabolismo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , AnimaisRESUMO
INTRODUCTION: Tuberculous lymphadenitis (TBLN) is the most common infectious etiology of peripheral lymphadenopathy in adults, in Turkiye. This study aimed to identify the demographic, clinical, and laboratory variables that differentiate TBLN from non-tuberculous lymphadenitis (NTBLN), as well as the etiology of lymphadenopathy in adults. METHODOLOGY: Patients who were over 18 years old and were referred to the infectious disease outpatient clinics with complaints of swollen peripheral lymph nodes, and who underwent lymph node biopsy between 1 January 2010 and 1 March 2021, were included in this multicenter, nested case-control study. RESULTS: A total of 812 patients at 17 tertiary teaching and research hospitals in Turkiye were included in the study. TBLN was the most frequent diagnosis (53.69%). The proportion of patients diagnosed with TBLN was higher among females; and among those who had a higher erythrocyte sedimentation rate, positive purified protein derivative test, and positive interferon-gamma release test result (p < 0.05). However, TBLN was less frequent among patients with generalized lymphadenopathy, bilateral lymphadenopathy, axillary lymphadenopathy, inguinal lymphadenopathy, hepatomegaly, splenomegaly, leukocytosis, and moderately increased C reactive protein levels (p < 0.05). CONCLUSIONS: Identifying the variables that predict TBLN or discriminate TBLN from NTBLN will help clinicians establish optimal clinical strategies for the diagnosis of adult lymphadenopathy.
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Tuberculose dos Linfonodos , Humanos , Tuberculose dos Linfonodos/diagnóstico , Feminino , Masculino , Adulto , Estudos de Casos e Controles , Pessoa de Meia-Idade , Adulto Jovem , Turquia/epidemiologia , Linfonodos/patologia , Adolescente , Linfadenopatia/diagnóstico , Linfadenopatia/etiologia , Idoso , Testes de Liberação de Interferon-gama/métodosRESUMO
Breast cancer remains a major global health issue, particularly affecting women and contributing significantly to mortality rates. Current treatments for estrogen receptor-positive breast cancers, such as aromatase inhibitors, are effective but often come with side effects and resistance issues. This study addresses these gaps by targeting aromatase, an enzyme crucial for estrogen synthesis, which plays a pivotal role in breast cancer progression. The innovative approach involves synthesizing novel bis-triazolopyridopyrimidines, designed to leverage the combined pharmacological benefits of pyridopyrimidine and 1,2,4-triazole structures, known for their potent aromatase inhibition and anti-cancer properties. These compounds were synthesized and characterized using 1H-NMR, 13C-NMR, and MS spectral analyses, and their anticancer efficacy was evaluated through MTT assays against MCF-7 breast cancer cell lines inâ vitro. Molecular docking analyses revealed strong binding energies with aromatase, particularly for compounds 5 b, 5 c, 10 a, and 10 b, indicating their potential as effective aromatase inhibitors. The study highlights these compounds as promising candidates for further development as therapeutic agents against breast cancer.
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Echinochasmidae are considered one of the digenean intestinal parasites of carnivorous mammals and humans. Some larvicidal medications, such as praziquantel and albendazole, were employed to interrupt the life cycle of Echinochasmidae, which may cause harmful and serious effects on the domestic fish, ducks, and humans in our ecosystem. Cercariae of Echinochasmus sp. (gymnocephalus type) were harvested by exposing snails to strong artificial illumination. The emerging cercariae were exposed in vitro to different concentrations of praziquantel and albendazole at the same period of incubation 12 h. Using probit analysis in SPSS version 25, the lethal concentrations 50 and 95% were determined. They were 0.036 and 0.82 ppm, respectively, for praziquantel and 5.3 and 9.2 ppm, respectively, for albendazole. The ultrastructural changes using scanning electron microscope on the tegumental surface of the treated cercariae with the two drugs were compared to the untreated cercariae. The untreated cercariae have a pear-shaped body with a long tail. The oral sucker is armed with a spiny collar and decorated with ciliated and unciliated sensory papillae. The cardinal ventral sucker has a thick, muscular wall. The cercarial tail is decorated with parallel longitudinal tegumental processes and spherical, unciliated papillae. In comparisons, cercariae treated with both drugs lost all healthy morphological features, but in varying degrees and effects between the two drugs. Our findings suggest that the use of both drugs can be recommended during the design of control strategies to combat this type of intestinal parasite.
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OBJECTIVE: We sought to examine outcomes of ultrafiltration in real world community-based hospital settings. BACKGROUND: Ultrafiltration (UF) is an accepted therapeutic option for advanced decompensated heart failure (ADHF). the feasibility of UF in a community hospital setting, by general cardiologists in a start-up program had not been objectively evaluated. METHODS: We retrospectively analyzed the first-year cohort of ADHF patients treated with UF from 10/1/2019 to 10/1/2020, which totaled 30 patients, utilizing the CHF Solutions Aquadex FlexFlow™ System with active UF rate titration. RESULTS: Baseline patient characteristics were similar to RCTs: mean age 63, 73 % male; 27 % female; 53 % Caucasian; 47 % African American; 77 % had LVEF ≤ 40. The baseline mean serum creatinine (Cr) was 1.84 ±0.62 mg/dL, mean GFR of 36.95 ±9.60 ml/min. HF re-admission rates were not significantly different than prior studies (17.2 % at 30 d, 23.3 % at 60 d, but in our cohort, per patient HF re-admission rates were reduced significantly by 60 d (0.30 p = 0.017). CONCLUSION: Our analysis showed success with UF in mainstream setting with reproducible results of significant volume loss without adverse renal effect, mitigation of recurrent Hdmissions, and remarkable subjective clinical benefit.
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Dimensionally stable anodes of titanium (Ti) metal coated with mixed metal oxides (MMO) are widely used in several electrochemical applications, especially chloro-alkali electrolysis. Herein, we deposited MMO coatings on Ti substrates in different compositions, namely, (60%RuO2-40%TiO2), (60%RuO2-30%TiO2-10%IrO2), and (60%RuO2-20%TiO2-15%IrO2-5%Ta2O5), where RuO2 has the same percentage ratio in all coatings. The aim was to use these electrodes for chlorine evolution reaction (CER) and oxygen evolution reaction (OER) applications. Electrochemical characterization of the coated samples was performed to identify the best Ti/MMO electrodes with the highest efficiencies among the various prepared combinations. The role of IrO2 and Ta2O5 in enhancing corrosion resistance and electrochemical efficacy was up for debate. Scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) analyses were exploited to determine the surface morphology, chemical composition, crystallinity, surface composition, and chemical states of the acquired coatings. The differential scanning calorimetry (DSC) method was used to evaluate the apparent activation energy ( E a ) of the deposited MMO. Additionally, the electrochemical performance of our designed coatings was scrutinized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), a current on-off test, a CV stability test (ST), and an accelerated stability test (AST). Furthermore, linear sweep voltammetry (LSV) was incorporated to assess the catalytic efficacy of the prepared anodes toward the CER in a brine solution of pH 2 and the OER in 1 M H2SO4. It became clear that the CER and OER incurred almost the same potential value (1.1 V) on both Ti/RuO2-TiO2 and Ti/RuO2-TiO2-IrO2 electrodes. However, on the Ti/RuO2-TiO2-IrO2-Ta2O5 anode, there was a 0.2 V potential difference between the CER occurring at 1.1 V and the OER happening at 1.3 V.
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Targeted covalent inhibitors (TCIs) have witnessed a significant resurgence in recent years, particularly in the kinase drug discovery field for treating diverse clinical indications. The inhibition of Bruton's tyrosine kinase (BTK) for treating B-cell cancers is a classic example where TCIs such as ibrutinib have had breakthroughs in targeted therapy. However, selectivity remains challenging, and the emergence of resistance mutations is a critical concern for clinical efficacy. Computational methods that can accurately predict the impact of mutations on inhibitor binding affinity could prove helpful in informing targeted approachesâproviding insights into drug resistance mechanisms. In addition, such systems could help guide the systematic evaluation and impact of mutations in disease models for optimal experimental design. Here, we have employed in silico physics-based methods to understand the effects of mutations on the binding affinity and conformational dynamics of select TCIs of BTK. The TCIs studied include ibrutinib, acalabrutinib, and zanubrutinibâall of which are FDA-approved drugs for treating multiple forms of leukemia and lymphoma. Our results offer useful molecular insights into the structural determinants, thermodynamics, and conformational energies that impact ligand binding for this biological target of clinical relevance.
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Tirosina Quinase da Agamaglobulinemia , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Tirosina Quinase da Agamaglobulinemia/genética , Conformação Molecular , Mutação , /farmacologiaRESUMO
Estrogens have proven to be effective in bovine estrus induction protocols. Considering the extensive use of these products in large-scale estrus synchronization, the primary objective of the present study was to assess their effects on pregnancy rate (PR) using a meta-analysis approach. A total of 797 papers were screened from three major databases (PubMed, Web of Science, Scopus). Sixty-one studies were eligible for inclusion in the meta-analysis. The pregnancy status (success or failure) at 30 days post-insemination was considered as the effect size data. The odds ratios (OR) of PR were evaluated by considering the effects of estrogens in groups with or without estrogen intervention. The impact of estrogen (including factors such as type, dose, and time of administration) and animal characteristics (such as breed, type, and parity) was taken into account when assessing the effectiveness of estrogen response as PR. The results showed an OR of 1.25 (95% CI: 1.15-1.36; P = 0.000) for PR in animals that received estrogen compared to cattle that did not receive estrogen. Estradiol benzoate (OR = 1.3) and estradiol cypionate (OR = 1.2), with doses ranging from 1 to 3 mg (OR = 1.13-1.7), significantly increased the OR of PR. In terms of PR, beef cattle exhibited a higher odds ratio (OR = 1.4; P = 0.000) compared to dairy cattle (OR = 1.1; P = 0.09). The administration of estrogens in the estrus synchronization protocol significantly improved PR in both artificial insemination (OR = 1.2; P = 0.000) and embryo transfer (OR = 1.3; P = 0.033) programs. In summary, incorporating estrogens into estrus induction protocols led to an enhancement of the OR of PR among cattle.
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Estrogênios , Progesterona , Feminino , Gravidez , Bovinos , Animais , Estrogênios/farmacologia , Taxa de Gravidez , Progesterona/farmacologia , Estradiol/farmacologia , Estro/fisiologia , Sincronização do Estro/métodos , Inseminação Artificial/veterinária , Inseminação Artificial/métodos , Dinoprosta/farmacologia , Hormônio Liberador de Gonadotropina/farmacologiaRESUMO
Vitamin D deficiency is a globally recognized health concern, with particular prominence in specific geographies and demographics. Saudi Arabia, with its unique climatic conditions and cultural practices, has been under scrutiny regarding the prevalence of this deficiency, especially among children and adolescents. This systematic review aimed to assess the prevalence of vitamin D deficiency among children and adolescents in Saudi Arabia by compiling and analyzing various studies to offer a comprehensive view of the situation. The comprehensive web search encompassed a range of databases, including Google Scholar and PubMed, to gather studies published between 2012 and 2023. An analysis was conducted on seven studies, totaling 2,429 participants, with each study focusing on various aspects, regions, and cohorts within Saudi Arabia. These studies employed different methodologies, ranging from cross-sectional surveys to randomized clinical trials. The review unveiled an alarming prevalence of vitamin D deficiency in the studied population. On average, around 81.1% of children and adolescents showcased inadequate vitamin D levels. Specific vulnerable groups, such as those with Type 1 diabetes mellitus or asthma, had pronounced deficiencies. Factors influencing these levels ranged from dietary habits, sun exposure, physical activity, and socioeconomic parameters. The compelling evidence from the studies underscores a consistent health issue among the pediatric population in Saudi Arabia that the overwhelming majority of Saudi children and adolescents lack adequate vitamin D. Addressing this widespread deficiency needs a multifaceted approach. Implementing policies that support vitamin D food fortification, encouraging routine screenings, and launching public awareness campaigns about safe sun exposure and diet can play a transformative role in this health crisis.
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This study examined the influence of cariogenic environments on the surface roughness of ion-releasing restorative materials (IRMs). Custom-made stainless steel molds with holes of 5 mm × 2mm were used to fabricate 60 disc-shaped specimens of each of the following materials: Activa Bioactive (AV), Beautifil Bulk Restorative (BB), Cention N (Bulk-fill) (CN), and Filtek Z350XT (FZ) (Control). Baseline surface roughness (Ra) measurements were obtained using an optical 3D measurement machine (Alicona Imaging GmbH, Graz, Austria). The specimens were then randomly divided into five subgroups (n=12) and exposed to 10 ml of the following mediums at 37°C: distilled water (DW), demineralization solution (DM), remineralization solution (RM), pH cycling (PC) and air (AR) (control). Ra measurements were again recorded after one week and one month, followed by statistical evaluations with two-way analysis of variance (ANOVA) to determine interactions between materials and mediums. One-way ANOVA and post hoc Games Howell tests were performed for intergroup comparisons at a significance level of 0.05. Mean Ra values ranged from 0.085 ± 0.004 (µm) to 0.198 ± 0.001 µm for the various material-medium combinations. All IRMs showed significant differences in Ra values after exposure to the aqueous mediums. The smoothest surfaces were observed in the AR for all materials. When comparing materials, AV presented the roughest surfaces for all mediums. All IRM materials showed increased surface roughness over time in all cariogenic environments but were below the threshold value for bacterial adhesion, except for AV 1-month post immersion with pH cycling. Therefore, besides AV, the surface roughness of IRMs did not deteriorate to an extent that it is clinically relevant.
Assuntos
Resinas Compostas , Materiais Dentários , Resinas Compostas/uso terapêutico , Teste de Materiais , Água , Aderência Bacteriana , Propriedades de SuperfícieRESUMO
This study investigates the potential of using bacteriophages to control foodborne pathogen biofilms on stainless steel surfaces in the food industry. Biofilm-forming bacteria can attach to stainless steel surfaces, rendering them difficult to eradicate even after a thorough cleaning and sanitizing procedures. Bacteriophages have been proposed as a possible solution, as they can penetrate biofilms and destroy bacterial cells within, reducing the number of viable bacteria and preventing the growth and spread of biofilms. This systematic review and meta-analysis evaluates the potential of bacteriophages against different biofilm-forming foodborne bacteria, including Cronobacter sakazakii, Escherichia coli, Staphylococcus aureus, Pseudomonas fluorescens, Pseudomonas aeruginosa and Listeria monocytogenes. Bacteriophage treatment generally causes a significant average reduction of 38 % in biofilm formation of foodborne pathogens on stainless steel. Subgroup analyses revealed that phages are more efficient in long-duration treatment. Also, applying a cocktail of phages is 1.26-fold more effective than applying individual phages. Phages at concentrations exceeding 107 PFU/ml are significantly more efficacious in eradicating bacteria within a biofilm. The antibacterial phage activity decreases substantially by 3.54-fold when applied at 4 °C compared to temperatures above 25 °C. This analysis suggests that bacteriophages can be a promising solution for controlling biofilms in the food industry.
RESUMO
BACKGROUND AND AIMS: Video analysis has emerged as a potential strategy for performance assessment and improvement. We aimed to develop a video-based skill assessment tool for peroral endoscopic myotomy (POEM). METHODS: POEM was deconstructed into basic procedural components through video analysis by an expert panel. A modified Delphi approach and 2 validation exercises were conducted to refine the POEM assessment tool (POEMAT). Twelve assessors used the final POEMAT version to grade 10 videos. Fully crossed generalizability (G) studies investigated the contributions of assessors, endoscopists' performance, and technical elements to reliability. G coefficients below .5 were considered unreliable, between .5 and .7 as modestly reliable, and above .7 as indicative of satisfactory reliability. RESULTS: After task deconstruction, discussions, and the modified Delphi process, the final POEMAT comprised 9 technical elements. G analysis showed low variance for endoscopist performance (.8%-24.9%) and high interrater variability (range, 63.2%-90.1%). The G score was moderately reliable (≥.60) for "submucosal tunneling" and "myotomy" and satisfactorily reliable (≥.70) for "active hemostasis" and "mucosal closure." CONCLUSIONS: We developed and established initial content and response process validity evidence for the POEMAT. Future steps include appraisal of the tool using a wider range of POEM videos to establish and improve the discriminative validity of this tool.