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The term "inflammatory bowel disease" (IBD) describes a class of relapse-remitting conditions that affect the gastrointestinal (GI) tract. Among these, Crohn's disease (CD) and ulcerative colitis (UC) are two of the most globally prevalent and debilitating conditions. Several articles have brought attention to the significant role that inflammation and oxidative stress cooperatively play in the development of IBD, offering a different viewpoint both on its etiopathogenesis and on strategies for the effective treatment of these conditions. Marine ecosystems may be a significant source of physiologically active substances, supporting the search for new potential clinical therapeutics. Based on this evidence, this review aims to comprehensively evaluate the activity of marine algae and deriving biomolecules in decreasing pathological features of CD and UC. To match this purpose, a deep search of the literature on PubMed (MEDLINE) and Google Scholar was performed to highlight primary biological mechanisms, the modulation of inflammatory and oxidative stress biochemical parameters, and potential clinical benefits deriving from marine species. From our findings, both macroalgae and microalgae have shown potential as therapeutic solutions for IBD due to their bioactive compounds and their anti-inflammatory and antioxidant activities which are capable of modulating markers such as cytokines, the NF-κB pathway, reactive oxidative and nitrosative species (ROS and RNS), trefoil factor 3 (TFF3), lactoferrin, SIRT1, etc. However, while we found promising preclinical evidence, more extensive and long-term clinical studies are necessary to establish the efficacy and safety of marine algae for IBD treatment.
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Enfermedades Inflamatorias del Intestino , Estrés Oxidativo , Humanos , Estrés Oxidativo/efectos de los fármacos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/metabolismo , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Biomarcadores/metabolismo , Algas Marinas/química , Microalgas/química , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Organismos Acuáticos , Inflamación/tratamiento farmacológicoRESUMEN
Yield stability, alongside high yield potential and broad adaptation to various agroclimatic environments, is a key objective for rice breeders aiming to ensure food security. This study aimed to explore the most suitable and stable Boro rice genotypes for Bangladesh. Ten Boro rice genotypes underwent testing in four environments during the 2022 Boro season to investigate genotype-environment interaction (GEI) and yield stability performance. The experiment utilized three replications of a completely randomized block design. Yield stability performance was assessed through combined analysis and the additive main effects and multiplicative interaction (AMMI) model. The combined ANOVA revealed that the environment explained 10.23%, while GEI accounted for 9.17%, and the genotypes captured 80.60% of the variance, significantly impacting grain yield. Significance was observed in the environment, genotype main effects, and GEI. Analysis indicated that BRRI dhan 68 yielded the highest (6,754 kg·ha-1) and BRRI dhan 88 the lowest (5,620 kg·ha-1) among the investigated genotypes. In addition, genotypes BRRI dhan 84, BRRI dhan 81, and BRRI dhan 67 exhibited the highest grain yields. The Rangpur environment demonstrated considerable stability across the four environments with a high mean value of grain yield (7,206 kg·ha-1). Therefore, the AMMI model emerges as a valuable tool for identifying the most suitable and stable Boro rice genotypes with high-yielding potential across various regions in Bangladesh, as well as under diverse conditions.
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Background: Vitamin D binding protein (DBP) might increase substantially after ovarian stimulation and hence could be associated with IVF/ICSI outcomes because it determines the fraction of free bioavailable 25(OH) vitamin D. In this study, we aim to determine whether DBP is associated with E2 level after ovarian stimulation and IVF/ICSI outcomes. Design: Post-hoc analysis of a prospective observational cohort. Setting: Single-center study. Participants: 2569 women receiving embryo transfer. Intervention: None. Main outcome measures: The main outcomes were oocyte and embryo quality as well as pregnancy outcomes. Results: DBP concentration correlates with E2 on hCG day (=day of inducing ovulation with hCG; correlation coefficient r = 0.118, P<0.001) and E2 x-fold change to baseline level (r = 0.108, P<0.001). DBP is also positively correlated with total 25(OH)D (r = 0.689, R2 = 0.475, P<0.001) and inversely with free 25(OH)D (r=-0.424, R2=0.179, P<0.001), meaning that E2-stimulated DBP synthesis results in a decrease of free 25(OH)D during ovarian stimulation. However, such alteration does not affect IVF/ICSI outcomes when considering confounding factors, such as the number and quality of oocytes nor embryo quality as well as pregnancy outcomes. Conclusion: DBP concentration correlates with the degree of E2 increase after ovarian stimulation. DBP is also positively correlated with total 25(OH)D and inversely with free 25(OH)D, suggesting that the proportion of free 25(OH)D decreases during ovarian stimulation caused by E2-stimulated DBP synthesis. However, such alteration does not affect clinical IVF/ICSI outcomes.
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Gonadotropina Coriónica , Fertilización In Vitro , Inducción de la Ovulación , Ovulación , Resultado del Embarazo , Proteína de Unión a Vitamina D , Humanos , Femenino , Embarazo , Proteína de Unión a Vitamina D/sangre , Adulto , Inducción de la Ovulación/métodos , Gonadotropina Coriónica/administración & dosificación , Ovulación/efectos de los fármacos , Estudios Prospectivos , Fertilización In Vitro/métodos , Estrógenos/administración & dosificación , Transferencia de Embrión , Índice de Embarazo , Inyecciones de Esperma IntracitoplasmáticasRESUMEN
Parkinson's disease (PD) is recognized as the second most common neurodegenerative disease worldwide. Even if PD etiopathogenesis is not yet fully understood, in recent years, it has been advanced that a chronic state of inflammation could play a decisive role in the development of this pathology, establishing the close link between PD and neuroinflammation. In the broad panorama of inflammation and its several signaling pathways, the C-C chemokine receptor type 1 (CCR1) could play a key pathogenic role in PD progression, and could constitute a valuable target for the development of innovative anti-PD therapies. In this study, we probed the neuroprotective properties of the CCR1 antagonist BX471 compound in a mouse model of MPTP-induced nigrostriatal degeneration. BX471 treatments were performed intraperitoneally at a dose of 3 mg/kg, 10 mg/kg, and 30 mg/kg, starting 24 h after the last injection of MPTP and continuing for 7 days. From our data, BX471 treatment strongly blocked CCR1 and, as a result, decreased PD features, also reducing the neuroinflammatory state by regulating glial activation, NF-κB pathway, proinflammatory enzymes, and cytokines overexpression. Moreover, we showed that BX471's antagonistic action on CCR1 reduced the infiltration of immune cells, including mast cells and lymphocyte T activation. In addition, biochemical analyses carried out on serum revealed a considerable increase in circulating levels of CCR1 following MPTP-induced PD. In light of these findings, CCR1 could represent a useful pathological marker of PD, and its targeting could be a worthy candidate for the future development of new immunotherapies against PD.
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Enfermedad de Parkinson , Receptores CCR1 , Receptores CCR1/metabolismo , Receptores CCR1/antagonistas & inhibidores , Animales , Ratones , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Masculino , Modelos Animales de Enfermedad , Biomarcadores , Ratones Endogámicos C57BL , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Transducción de Señal/efectos de los fármacosRESUMEN
Objective: To compare the efficacy of tadalafil alone, dapoxetine alone, and tadalafil with dapoxetine as a combination therapy for the treatment of premature ejaculation. Patients and Methods: Eligible patients attended our andrology clinic with premature ejaculation were randomly allocated into three groups: group A (92 participants) received on-demand tadalafil, 5 mg; group B (91 participants) were given on-demand dapoxetine, 30 mg; and group C (89 participants) received on-demand combination of tadalafil, 5 mg, and dapoxetine, 30 mg. We assessed the changes in the intravaginal ejaculatory latency time (IELT) and the satisfaction scores 1, 2, and 3 months after treatment. Results: Highly statistically significant improvements were found in the mean IELT and satisfaction scores 1, 2, and 3 months post-treatment in all groups (P = <0.001). Post hoc analysis suggested this improvement was more pronounced in group C (P < 0.001). Conclusion: Both tadalafil and dapoxetine are effective in the treatment of patients with premature ejaculation, but the combination of both drugs gives better results.
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Indole-chalcone hybrids have burst into prominence as potent weapons in the battle against pain and inflammation due to their unique features, allowing these ligands to form pivotal interactions with biological targets. In this context, the base-catalyzed Claisen-Schmidt condensation of 3',4'-(methylenedioxy)acetophenone with heteroaromatic aldehydes carrying an indole scaffold yielded new chalcones (1-7). The central and peripheral antinociceptive activities of all chalcones (compounds 1-7) at the dose of 10 mg/kg (i.p.) were evaluated by hot plate (supraspinal response), tail immersion (spinal response), and acetic acid-induced writhing tests in mice. The anti-inflammatory activities of compounds 1-7 were also investigated by means of a carrageenan-induced mouse paw edema model. The results revealed that compounds 1-7 extended the latency of response to thermal stimulus significantly in a hot-plate test similar to dipyrone (300 mg/kg; i.p.), the positive control drug. However, only compounds 2-7 were found to be significantly effective in the tail-immersion test. Compounds 1-7 also significantly showed analgesic effect by reducing the number of writhes and anti-inflammatory activity by inhibiting edema formation at different time intervals and levels. 1-(1,3-Benzodioxol-5-yl)-3-(1-methyl-1H-indol-2-yl)prop-2-en-1-one (4) drew attention by providing the highest efficacy results in both acute analgesia and inflammation models. Based on the in silico data acquired from the QikProp module, compound 4 was predicted to possess favorable oral bioavailability and drug-like properties. Taken together, it can be concluded that chalcones (1-7), especially compound 4, are outstanding candidates for further research to investigate their potential use in the management of pain and inflammation.
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BACKGROUND: Hypertrophic cardiomyopathy is a genetic, life-threatening cardiovascular disease that often goes unidentified in pediatric patients. Patients are often asymptomatic and neither history or physical examination are reliable to detect the disease. The only reliable method to diagnose hypertrophic cardiomyopathy is with echocardiography to look at interventricular septal thickness. Emerging literature has shown that cardiac point-of-care ultrasound (POCUS) performed by pediatric emergency medicine (PEM) physicians is as effective and accurate compared with cardiac echocardiography performed by pediatric cardiologists. OBJECTIVE: The objective of the study was to determine the diagnostic accuracy of POCUS performed by ultrasound-trained PEM physicians in measuring the interventricular septum end diastole (IVSd) thickness in the pediatric emergency department. METHODS: We conducted a prospective, single-center, observational, diagnostic accuracy study to examine the diagnostic accuracy of POCUS in measuring IVSd thickness in pediatric patients who presented to the pediatric emergency department with symptoms that prompted a cardiac POCUS. Cardiac POCUS findings were interpreted by a PEM physician at the bedside and retrospectively by a pediatric cardiologist. Diagnostic concordance of the measurements obtained by the PEM physician and cardiologist was assessed. RESULTS: Forty-eight patients were enrolled. Median patient age was 13.4 years. There was excellent diagnostic agreement on the measurement of the IVSd thickness between PEM physicians and the pediatric cardiologist (81.25% of cases; 39/48). Disagreement was seen in 18.75% of the cases (9/48). The mean error of disagreement was -0.32, with a 95% confidence interval of -0.37 to -0.28. Overall, the mean error of both agreement and disagreement was -0.046, with 95% confidence interval of -0.08 to -0.01 and P value of 0.008. CONCLUSIONS: Point-of-care ultrasound performed by ultrasound-trained PEM physicians to measure pediatric IVSd thickness has a high diagnostic accuracy with excellent agreement with a pediatric cardiologist.
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Cardiomiopatía Hipertrófica , Ecocardiografía , Servicio de Urgencia en Hospital , Sistemas de Atención de Punto , Humanos , Estudios Prospectivos , Masculino , Femenino , Niño , Adolescente , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Ecocardiografía/métodos , Tabique Interventricular/diagnóstico por imagen , Preescolar , LactanteRESUMEN
Sclerostin (SOST) is produced by osteocytes and is known as a negative regulator of bone homeostasis. Parathyroid hormone (PTH) regulates calcium, phosphate as well as vitamin D metabolism, and is a strong inhibitor of SOST synthesis in vitro and in vivo. PTH has two methionine amino acids (positions 8 and 18) which can be oxidized. PTH oxidized at Met18 (Met18(ox)-PTH) continues to be bioactive, whereas PTH oxidized at Met8 (Met8(ox)-PTH) or PTH oxidized at Met8 and Met18 (Met8, Met18(di-ox)-PTH) has minor bioactivity. How non-oxidized PTH (n-oxPTH) and oxidized forms of PTH act on sclerostin synthesis is unknown. The effects of n-oxPTH and oxidized forms of PTH on SOST gene expression were evaluated in UMR106 osteoblast-like cells. Moreover, we analyzed the relationship of SOST with n-oxPTH and all forms of oxPTH in 516 stable kidney transplant recipients using an assay system that can distinguish in clinical samples between n-oxPTH and the sum of all oxidized PTH forms (Met8(ox)-PTH, Met18(ox)-PTH, and Met8, Met18(di-ox)-PTH). We found that both n-oxPTH and Met18(ox)-PTH at doses of 1, 3, 20, and 30 nmol/L significantly inhibit SOST gene expression in vitro, whereas Met8(ox)-PTH and Met8, Met18(di-ox)-PTH only have a weak inhibitory effect on SOST gene expression. In the clinical cohort, multivariate linear regression showed that only n-oxPTH, but not intact PTH (iPTH) nor oxPTH, is independently associated with circulating SOST after adjusting for known confounding factors. In conclusion, only bioactive PTH forms such as n-oxPTH and Met18(ox)-PTH, inhibit SOST synthesis.
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Proteínas Adaptadoras Transductoras de Señales , Proteínas Morfogenéticas Óseas , Hormona Paratiroidea , Hormona Paratiroidea/metabolismo , Humanos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Marcadores Genéticos , Animales , Osteoblastos/metabolismo , Osteoblastos/efectos de los fármacos , Masculino , Oxidación-Reducción , Femenino , Ratas , Metionina/metabolismo , Metionina/farmacología , Línea Celular , Persona de Mediana EdadRESUMEN
It has been suggested that the novel selective phosphodiesterase 9 (PDE9) inhibitor may improve cardiac and renal function by blocking 3',5'-cyclic guanosine monophosphate (cGMP) degradation. 5/6 nephrectomized (5/6Nx) rats were used to investigate the effects of the PDE9 inhibitor (BAY 73-6691) on the heart and kidney. Two doses of BAY 73-6691 (1 mg/kg/day and 5 mg/kg/day) were given for 95 days. The 5/6Nx rats developed albuminuria, a decrease in serum creatinine clearance (Ccr), and elevated serum troponin T levels. Echocardiographic data showed that 5/6 nephrectomy resulted in increased fractional shortening (FS), stroke volume (SV), and left ventricular ejection fraction (EF). However, 95 days of PDE9 inhibitor treatment did not improve any cardiac and renal functional parameter. Histopathologically, 5/6 nephrectomy resulted in severe kidney and heart damage, such as renal interstitial fibrosis, glomerulosclerosis, and enlarged cardiomyocytes. Telmisartan attenuated renal interstitial fibrosis and glomerulosclerosis as well as improved cardiomyocyte size. However, except for cardiomyocyte size and renal perivascular fibrosis, BAY 73-6691 had no effect on other cardiac and renal histologic parameters. Pathway enrichment analysis using RNA sequencing data of kidney and heart tissue identified chronic kidney disease pathways, such as phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, complement and coagulation cascades, and nuclear factor kappa B (NF-κB) signaling pathway. PDE9i did not affect any of these disease-related pathways. Two dosages of the PDE9 inhibitor BAY 73-6691 known to be effective in other rat models have only limited cardio-renal protective effects in 5/6 nephrectomized rats.
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Corazón , Riñón , Nefrectomía , Animales , Masculino , Ratas , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Miocardio/metabolismo , Miocardio/patología , Nefrectomía/métodosRESUMEN
PURPOSE: To assess the frequency and the predictive factors of Acute Kidney injury (AKI) in patients undergoing percutaneous nephrolithotomy (PNL). METHODS: A prospective observational work. Demographic, preoperative laboratory data, stone characteristics, and intraoperative and postoperative data were gathered. Perioperative AKI had been defined as an elevation in serum creatinine by ≥ 0.3 mg/dl within 48 h, or ≥ 1.5 times baseline, or urine volume less than 0.5 ml/ kg/hour for 6 hours. A multivariate logistic regression analysis was performed to determine the predictive factors of AKI. ROC curves were utilized to determine the cutoff values of the risk variables. P-values were deemed statistically significant when they were less than 0.05. RESULTS: A total of 418 participants had been involved. The frequency of AKI was 13.9, and 17.2% of patients with AKI developed CKD. The risk factors were age > 46.5 years, smoking, BMI > 28.5 kg/m2, hypertension, diabetes, utilization of angiotensin-converting enzyme inhibitors (ACEI), haemoglobin < 10.8 gm/dl, baseline creatinine > 1.41 mg/dl, eGFR < 65.2 ml/min./1.73 m2, serum uric acid > 5.2 mg/dl, stone volume > 1748 mm3, large tract size, long operative time, and intra-operative bleeding. Patients with AKI had a notably extended duration of hospitalization (3.2 days ± 0.45 vs 2.1 ± 0.42, p < 0.001). CONCLUSIONS: Perioperative AKI occurred in 13.9% of individuals undergoing PNL. Identification and optimization of the risk factors and meticulous technique during PNL procedures should be attempted to decrease the risk of AKI.
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Lesión Renal Aguda , Nefrolitotomía Percutánea , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/epidemiología , Estudios Prospectivos , Nefrolitotomía Percutánea/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Factores de Riesgo , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Cálculos Renales/cirugía , Factores de Edad , Creatinina/sangre , AncianoRESUMEN
Millets are small-grained nutritious minor cereal crops that are resistant to different abiotic stresses resulting from climate change. Despite their many benefits, millets have received limited attention in agricultural research, policies, and markets. Considering the importance of millets, recently the government many tropical countries including India and Bangladesh give more emphasis to millets cultivation and improvement. Moreover, Food and Agricultural Organization of the United Nations (FAO) declared 2023 to be the "International Years of Millets". In these connections, a details and updated review of the pros and cons of millets cultivation and its improvement in this region warrant due attention. The review therefore, examines the potential and main barriers to the adoption and promotion of millet cultivation in this region. These include limited research and development efforts, inadequate infrastructure and inputs, weak market linkages and demand, and insufficient awareness and knowledge about millets' nutritional and environmental benefits. This review also highlighted the prospects and strategies for scaling up millet cultivation in this region especially in Bangladesh. These include increasing public and private investment in research and extension services, strengthening farmers' organizations and market linkages, promoting millet-based value chains and products, and integrating millets into nation's food policy. The review concludes that millets might support equitable and sustainable agricultural growth, which would contribute to global food and nutritional security and could help attain the sustainable development goals (SDGs). However, achieving this potential will require concerted efforts from multiple stakeholders, including farmers, researchers and policymakers. The review emphasizes the need for a multi-disciplinary and multi-stakeholder approach that prioritizes innovation, inclusiveness, and sustainability. Lastly, the review highlights more investigation into the socioeconomic, environmental, and nutritional effects of millet production in this region with special emphasis on Bangladesh in order to support evidence-based policies and practices.
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Series of novel 1,2,3-triazole, and 1,2,3- triazoline glycosides (a-e) were efficiently synthesized starting from d-arabinose in an effort to synthesize a new type of hybrid molecules containing sugar azide. The key step involved is the introduction of a new group, ethylene glycol, to the anomeric site and protection of the hydroxyl groups with acetic anhydride. Following that, the acetyl group is converted into ethylene glycol to tosylate. Compound Azido ethyl-O-ß-d-arabinofuranoside 4 was synthesized with good yield by treating the derivative 3 with sodium azide, which displaced the tosylate 3 and replaced it with the azide group. The new glycosides were synthesized via a 1,3-dipolar cycloaddition reaction between the intermediate compound 4 and several alkenes and alkynes. The triazole and triazoline compounds were characterized by FT-IR, 1H NMR, 13C NMR, LC/MS-IT-TOF spectral, and C·H.N. analysis. The antimicrobial screening was assayed using the disc diffusion technique revealed moderate to high potential inhibitory values against three test microorganisms compared to standard drugs. Their pharmacokinetics evaluation also showed promising drug-likeness and ADME properties. Furthermore, density functional theory (DFT) was utilized to obtain the molecular geometry of the title compounds utilizing B3LYP/6-311G++ (d, p), molecular electrostatic potential (MEP), frontier molecular orbitals (FMOs) through the investigation of HOMO and LUMO orbitals, and energy gap value. A lower energy gap value denotes that electrons can be transported more easily, indicating that molecule (b) is more reactive than other compounds. Molecular docking analysis revealed that all the designed triazole and triazoline glycosides interacted strongly inside the active site of the enzyme (PDB ID: 2Q85). and exhibits high docking scores, higher than the standard drug. The range of docking scores is -7.99 kcal/mol compound (a) to -7.42 kcal/mol compound (e).
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Glicósidos , Triazoles , Triazoles/farmacología , Triazoles/química , Simulación del Acoplamiento Molecular , Glicósidos/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , Azidas , Glicoles de EtilenoRESUMEN
Background: 25-hydroxyvitamin D (25(OH)D) and potentially also 1,25-dihydroxyvitamin D (1,25(OH)2D) inhibits the synthesis of parathyroid hormone (PTH) in the chief cells of the parathyroid gland. Clinical studies showing a negative correlation between (25(OH)D and PTH are in good agreement with these findings in basic science studies. However, PTH was measured in these studies with the currently clinically used 2nd or 3rd generation intact PTH (iPTH) assay systems. iPTH assays cannot distinguish between oxidized forms of PTH and non-oxidized PTH. Oxidized forms of PTH are the by far most abundant form of PTH in the circulation of patients with impaired kidney function. Oxidation of PTH causes a loss of function of PTH. Given that the clinical studies done so far were performed with an PTH assay systems that mainly detect oxidized forms of PTH, the real relationship between bioactive non-oxidized PTH and 25(OH)D as well as 1,25(OH)2D is still unknown. Methods: To address this topic, we compared for the first time the relationship between 25(OH)D as well as 1,25(OH)2D and iPTH, oxPTH as well as fully bioactive n-oxPTH in 531 stable kidney transplant recipients in the central clinical laboratories of the Charité. Samples were assessed either directly (iPTH) or after oxPTH (n-oxPTH) was removed using a column that used anti-human oxPTH monoclonal antibodies, a monoclonal rat/mouse parathyroid hormone antibody (MAB) was immobilized onto a column with 500 liters of plasma samples. Spearman correlation analysis and Multivariate linear regression were used to evaluate the correlations between the variables. Results: There was an inverse correlation between 25(OH)D and all forms of PTH, including oxPTH (iPTH: r=-0.197, p<0.0001; oxPTH: r=-0.203, p<0.0001; n-oxPTH: r=-0.146, p=0.001). No significant correlation was observed between 1,25(OH)2D and all forms of PTH. Multiple linear regression analysis considering age, PTH (iPTH, oxPTH and n-oxPTH), serum calcium, serum phosphor, serum creatinine, fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), albumin, and sclerostin as confounding factors confirmed these findings. Subgroup analysis showed that our results are not affected by sex and age. Conclusion: In our study, all forms of PTH are inversely correlated with 25-hydroxyvitamin D (25(OH)D). This finding would be in line with an inhibition of the synthesis of all forms of PTH (bioactive n-oxPTH and oxidized forms of PTH with minor or no bioactivity) in the chief cells of the parathyroid glad.
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Trasplante de Riñón , Hormona Paratiroidea , Animales , Ratones , Ratas , Calcifediol , Glándulas Paratiroides/metabolismoRESUMEN
Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic datasets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework stdpopsim seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of stdpopsim focused on establishing this framework using six well-characterized model species (Adrion et al., 2020). Here, we report on major improvements made in the new release of stdpopsim (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than threefold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed the best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to stdpopsim aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone.
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Genoma , Programas Informáticos , Simulación por Computador , Genética de Población , GenómicaRESUMEN
Inflammatory processes are increasingly attributed to macrophage polarization. Proinflammatory macrophages promote T helper (Th) 1 response, tissue repair, and Th2 responses. Detection of macrophages in tissue sections is facilitated by CD68. Our study is focused on the expression of CD68 and the estimation of proinflammatory cytokines in children's patients with chronic tonsillitis secondary to vitamin D supplementation. This hospital-based Randomized prospective case-control study was conducted on 80 children with chronic tonsillitis associated with vitamin D deficiency where (40 received vitamin D 50,000 IU weekly for 3-6 months and 40 received 5 ml distilled water as placebo). The serum 25-hydroxyvitamin D [25(OH)D] was measured using an Enzyme-linked immunosorbent assay on all included children. Different histological and immunohistochemical studies for the detection of CD68 were done. There was a significantly lower serum level of 25(OH)D in the placebo group versus the vitamin D group (P < 0.001). The levels of pro-inflammatory cytokines, TNFα, and IL-2 significantly increased in the placebo group as compared to the vitamin D group (P < 0.001). The increased level of IL-4 and IL-10 in the placebo group as compared to the vitamin D group was insignificant (P = 0.32, 0.82) respectively. Vitamin D supplementation alleviated the deleterious effect of chronic tonsillitis on the histological structure of the tonsil. Tonsillar tissues of the children in the control and vitamin D groups demonstrated a highly statistically significantly lower number of CD68 immunoexpressing cells compared with those in the placebo group (P < 0.001). Low vitamin D may play a role in chronic tonsillitis. Vitamin D supplementation could help reduce the occurrence of chronic tonsillitis in susceptible children.
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Tonsilitis , Deficiencia de Vitamina D , Niño , Humanos , Estudios de Casos y Controles , Colecalciferol , Citocinas , Suplementos Dietéticos , Vitamina D , VitaminasRESUMEN
A crop simulation model is adopted to calculate the potential yield in a certain location. The data sets generated in each scenario (2021-2022) were used to evaluate the InfoCrop model. A field experiment using a randomized complete block design was conducted at the Agronomy Department's research field, Hajee Mohammad Danesh Science and Technology University. The following two factors: 1) factor A: sowing dates (Planting date 1: PD1 = 5th November and Planting date 2: PD2 = 15th November 2021) and 2) factor B: Trichoderma biofertilizers (T1 = control, T2 = 50% chemical fertilizer + 2,000 kg ha-1 Trichoderma biofertlizer, T3 = fully chemical fertilizer; and T4 = fully 3,000 kg ha-1 Trichoderma biofertilizer). Three BARI (Bangladesh Agricultural Research Institute) released varieties (V1 = BARI Sarisa-14, V2 = BARI Sarisa-16, and V3 = BARI Sarisa-17) used for the completion of the experiment. The Trichoderma biofertilizer and planting dates had a significant influence on yield and yield attributes of mustard. Results showed that plant height, leaf width, leaves per plant, pods per plant, harvest index, maturity date, and yield were significantly affected by Trichoderma biofertilizer treatments, two different conditions, and varieties. The regression analysis indicated a significant linear relationship between two different growing conditions especially for harvest index PD2>PD1 (0.88>0.83), grain yield (0.94>0.90), flowering date (0.95>0.91) and maturity date (0.95>0.90). It was found that the model significantly overestimated all the parameters with an acceptable error range (<15%) while growth and yield characteristics including flowering and maturity dates and yield were simulated and results were compared to observed data. BARI Sarisa 16 had the highest simulated yield of 2.5 t ha-1 and showed a high yielding variety among the used varieties in the experiment. As a result, it can be concluded that if the InfoCrop growth model is carefully calibrated, it will be an excellent tool for evaluating and identifying the best yielding variety.
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Trichoderma , Humanos , Planta de la Mostaza , Fertilizantes/análisis , Agricultura/métodos , Grano ComestibleRESUMEN
BACKGROUND: Genetic-guided P2Y12 inhibitor selection has been proposed to reduce ischemic events by identifying CYP2C19 loss-of-function (LOF) carriers at increased risk with clopidogrel treatment after percutaneous coronary intervention (PCI). A prespecified analysis of TAILOR-PCI (Tailored Antiplatelet Therapy Following PCI) evaluated the effect of genetic-guided P2Y12 inhibitor therapy on cumulative ischemic and bleeding events. OBJECTIVES: Here, the authors detail a prespecified analysis of cumulative endpoints. The primary endpoint was cumulative incidence rate of ischemic events at 12 months. Cumulative incidence of major and minor bleeding was a secondary endpoint. Cox proportional hazards models as adapted by Wei, Lin, and Weissfeld were used to estimate the effect of this strategy on all observed events. METHODS: The TAILOR-PCI trial was a prospective trial including 5,302 post-PCI patients with acute and stable coronary artery disease (CAD) who were randomized to genetic-guided P2Y12 inhibitor or conventional clopidogrel therapy. In the genetic-guided group, LOF carriers were prescribed ticagrelor, whereas noncarriers received clopidogrel. TAILOR-PCI's primary analysis was time to first event in LOF carriers. RESULTS: Among 5,276 patients (median age 62 years; 25% women; 82% acute CAD; 18% stable CAD), 1,849 were LOF carriers (903 genetic-guided; 946 conventional therapy). The cumulative primary endpoint was significantly reduced in the genetic-guided group compared with the conventional therapy (HR: 0.61; 95% CI: 0.41-0.89; P = 0.011) with no significant difference in cumulative incidence of major or minor bleeding (HR: 1.36; 95% CI: 0.67-2.76; P = 0.39). CONCLUSIONS: Among CYP2C19 LOF carriers undergoing PCI, a genetic-guided strategy resulted in a statistically significant reduction in cumulative ischemic events without a significant difference in bleeding. (Tailored Antiplatelet Therapy Following PCI [TAILOR-PCI]; NCT01742117).
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Síndrome Coronario Agudo , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Femenino , Persona de Mediana Edad , Masculino , Clopidogrel/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Citocromo P-450 CYP2C19/genética , Intervención Coronaria Percutánea/efectos adversos , Estudios Prospectivos , Resultado del Tratamiento , Hemorragia/etiología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/complicaciones , Síndrome Coronario Agudo/terapia , Antagonistas del Receptor Purinérgico P2Y/efectos adversosRESUMEN
BACKGROUND: The quantitative relationship of incident cardiovascular disease (CVD) to lifetime cumulative risk factor exposure is not well understood. OBJECTIVES: Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we examined the quantitative associations of cumulative exposure over time to multiple, simultaneously operating risk factors with CVD incidence and the incidence of its components. METHODS: Regression models were developed quantifying the influence of the time course and severity of multiple CVD risk factors, operating simultaneously, on risk of incident CVD. The outcomes were incident CVD and the incidence of its components: coronary heart disease, stroke, and congestive heart failure. RESULTS: Our study included 4,958 asymptomatic adults enrolled in CARDIA from 1985 to 1986 (ages 18 to 30 years) who were followed for 30 years. Risk of incident CVD depends on the time course and severity of a series of independent risk factors, the impact of which is mediated by their effects on individual CVD components after age 40 years. Cumulative exposure (AUC vs time) to low-density lipoprotein cholesterol and triglycerides was independently associated with risk of incident CVD. Of the blood pressure variables, areas under the mean arterial pressure vs time curve and the pulse pressure vs time curve were strongly and independently associated with incident CVD risk. CONCLUSIONS: The quantitative description of the link between risk factors and CVD informs the construction of individualized CVD mitigation strategies, design of primary prevention trials, and assessment of public health impact of risk factor-based interventions.
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Enfermedades Cardiovasculares , Enfermedad Coronaria , Insuficiencia Cardíaca , Adulto Joven , Humanos , Adolescente , Adulto , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Factores de Riesgo , Insuficiencia Cardíaca/epidemiología , Presión Sanguínea/fisiología , IncidenciaRESUMEN
BACKGROUND: Modic changes (MC) of the vertebral endplates and facet joint degeneration are common causes of neck pain. No previous study has shown the prevalence of and relationship between MC and facet joint changes in cervical spondylotic myelopathy (CSM). The objective of this article was to study the endplate and facet joint changes in CSM. METHODS: Magnetic resonance imaging of the cervical spine in 103 patients with CSM was retrospectively evaluated. The scans were evaluated by 2 raters, who classified spinal segments according to the Modic classification and the degree of facet degeneration. RESULTS: In patients <50 years old, there were no MC in 61.5%. In patients with MC, Modic type II at C4-C5 was observed most frequently. MC were found in 71.4% of patients ≥50 years old. In patients with MC, Modic type II at C3-C4 was observed most frequently. Degenerative changes of the facet joints were found frequently in both patients <50 years old (77.5%) and patients ≥50 years (90.2%), and grade I degeneration was observed most frequently in both groups. There was a significant correlation between MC and facet joint changes. CONCLUSIONS: MC in the cervical spine are common magnetic resonance imaging findings in patients with CSM ≥50 years old. Degenerative facet joint changes are found in the majority of patients with CSM regardless of age. We found a significant correlation between MC and facet joint changes at the same level, indicating that both imaging findings are involved in a common pathophysiological pathway.