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Nitrate pollution threatens the Barva and Colima multi-aquifer system, the primary drinking water source in the Greater Metropolitan Area of Costa Rica. In addressing nitrate contamination dynamics, this study proposes an integrated approach by combining multivariate statistical analyses, hydrochemical parameters, sewage discharge, and regional land-use and land-cover patterns to assess the extent and degree of contamination, dominant biogeochemical processes, and refine the interpretation of nitrate sources previously derived solely from δ15NNO3 information. Over seven years (2015-2022), 714 groundwater samples from 43 sites were analyzed for nitrate and major ions, including two sampling campaigns for dissolved organic and inorganic carbon, nitrite, ammonium, FeTotal, MnTotal, and δ15NNO3 analyses. The findings presented elevated nitrate concentrations in urban and agricultural/urban areas, surpassing the Maximum Concentration Levels on several occasions, and oxidizing conditions favoring mineralization and nitrification processes in unconfined Barva and locally confined Upper Colima/Lower Colima aquifers. Similar nitrate contents and spatial patterns in agricultural and urban zones in the shallow Barva aquifer suggest comparable contributions from nitrogen fertilizers and urban wastewaters despite the gradual increase in urban land cover and the reduction of agricultural areas. Isotopic analyses and dissolved organic carbon (DOC) indicate a shift in nitrate sources from agricultural to urban areas in both Barva and Colima aquifers. Principal Component and Hierarchical Cluster Analyses link land use, nitrate sources, and water quality. Three distinct sample clusters aligned with forest/grassland, agricultural/urban, and urban land use, emphasizing the impact of anthropogenic activities on groundwater quality, even in the deeper Colima aquifers. The study challenges nitrate isotope mixing models, enhancing accuracy in identifying pollution sources and assessing the spatial extent of contamination by incorporating DOC and other hydrochemical parameters. Similar outcomes, with and without the use of nitrate isotopes, reinforce the usefulness of the integrated approach, providing a practical and cost-effective alternative.
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AIM: To evaluate the impact of aldosterone excess on renal function in individuals with primary aldosteronism and to compare its evolution after surgery or mineralocorticoid receptor antagonist (MRA) treatment. METHODS: A multicentre, retrospective cohort study of primary aldosteronism patients in follow-up in 36 Spanish tertiary hospitals, who underwent specific treatment for primary aldosteronism (MRA or adrenalectomy). RESULTS: A total of 789 patients with primary aldosteronism were included, with a median age of 57.5âyears and 41.8% being women. At primary aldosteronism diagnosis, the prevalence of chronic kidney disease (CKD) was 10.7% ( n â=â84), with 75% of cases classified as state 3a ( n â=â63). Primary aldosteronism patients with CKD had a longer duration of hypertension, a higher prevalence of type 2 diabetes, dyslipidaemia, cardiovascular events, hypokalaemia, and albuminuria. Unilateral adrenalectomy was performed in 41.8% of cases ( n â=â330), and 459 patients were treated with MRA. After a median follow-up of 30.7âmonths (range 13.3-68.4), there was a significant decline in the estimated glomerular filtration rate (eGFR) in operated patients and those receiving MRA. During follow-up, 24.4% of patients with CKD at the time of primary aldosteronism diagnosis had normalized renal function, and 39% of those with albuminuria had albuminuria remission. There were no differences in renal function or albuminuria regression between the two therapy groups. However, development of albuminuria was less common in operated than in medically treated patients (0 vs. 6.0%, P â=â0.009). CONCLUSION: CKD affects around 10% of the patients with primary aldosteronism, with a higher risk in individuals with long-term hypertension, type 2 diabetes, dyslipidaemia, cardiovascular events, hypokalaemia, and albuminuria. At short-term, both MRA and surgical treatment lead to a reduction of renal function, but adrenalectomy led to higher renal protection.
Subject(s)
Adrenalectomy , Hyperaldosteronism , Mineralocorticoid Receptor Antagonists , Registries , Humans , Hyperaldosteronism/complications , Hyperaldosteronism/physiopathology , Female , Male , Middle Aged , Spain/epidemiology , Retrospective Studies , Mineralocorticoid Receptor Antagonists/therapeutic use , Aged , Kidney/physiopathology , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/complications , Adult , Glomerular Filtration Rate , Cohort StudiesABSTRACT
Inherited retinal diseases, which include retinitis pigmentosa, are a family of genetic disorders characterized by gradual rod-cone degeneration and vision loss, without effective pharmacological treatments. Experimental approaches aim to delay disease progression, supporting cones' survival, crucial for human vision. Histone deacetylases (HDACs) mediate the activation of epigenetic and nonepigenetic pathways that modulate cone degeneration in RP mouse models. We developed new HDAC inhibitors (5a-p), typified by a tetrahydro-γ-carboline scaffold, characterized by high HDAC6 inhibition potency with balanced physicochemical properties for in vivo studies. Compound 5d (repistat, IC50 HDAC6 = 6.32 nM) increased the levels of acetylated α-tubulin compared to histone H3 in ARPE-19 and 661W cells. 5d promoted vision rescue in the atp6v0e1-/- zebrafish model of photoreceptor dysfunction. A single intravitreal injection of 5d in the rd10 mouse model of RP supported morphological and functional preservation of cone cells and maintenance of the retinal pigment epithelium array.
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The present study assesses the effect of culinary treatment and gastrointestinal digestion upon the release of additives present in microplastics. Organic additives were determined by gas chromatography-mass spectrometry, and inorganic additives using inductively coupled plasma-mass spectrometry. The results revealed a large number of organic additives in the plastic samples, some being classified as possible carcinogens. Contents of Sb in PET (polyethylene terephthalate), Zn and Ba in LDPE (low-density polyethylene) and PVC (polyvinylchloride), and Ti and Pb in LDPE were also noteworthy. The culinary process promotes the release and solubilization of additives into the cooking liquid, with phthalates, benzophenone, N-butylbenzenesulfonamide (NBBS) and bisphenol A being of particular concern. The solubilization of phthalates and NBBS was also observed during gastrointestinal digestion. This study demonstrates that culinary treatment and gastrointestinal digestion promote release and solubilization of additives from plastics ingested with the diet. Such solubilization may facilitate their entry into the systemic circulation.
Subject(s)
Microplastics , Microplastics/chemistry , Microplastics/toxicity , Humans , Cooking , Digestion , Food Contamination/analysis , Gastrointestinal Tract/metabolismABSTRACT
Recently, intermittent fasting has gained relevance as a strategy to lose weight and improve health as an alternative to continuous caloric restriction. However, the metabolic impact and the sex-related differences are not fully understood. The study aimed to compare the response to a continuous or intermittent caloric restriction in male and female rats following a previous induction of obesity through a cafeteria diet by assessing changes in body weight, energy intake, metabolic parameters, and gene expression in liver hepatic and adipose tissue. The continuous restriction reduced the energy available by 30% and the intermittent restriction consisted of a 75% energy reduction on two non-consecutive days per week. The interventions reduced body weight and body fat in both sexes, but the loss of WAT in females was more marked in both models of caloric restriction, continuous and intermittent. Both caloric restrictions improved insulin sensitivity, but more markedly in females, which showed a more pronounced decrease in HOMA-IR score and an upregulation of hepatic IRS2 and Sirt1 gene expression that was not observed in males. These findings suggest the fact that females are more sensitive than males to reduced caloric content in the diet.
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Diet , Intermittent Fasting , Female , Male , Animals , Rats , Obesity/etiology , Food , Caloric RestrictionABSTRACT
A wide range of approaches can be used to detect micro RNA (miRNA)-target gene pairs (mTPs) from expression data, differing in the ways the gene and miRNA expression profiles are calculated, combined and correlated. However, there is no clear consensus on which is the best approach across all datasets. Here, we have implemented multiple strategies and applied them to three distinct rare disease datasets that comprise smallRNA-Seq and RNA-Seq data obtained from the same samples, obtaining mTPs related to the disease pathology. All datasets were preprocessed using a standardized, freely available computational workflow, DEG_workflow. This workflow includes coRmiT, a method to compare multiple strategies for mTP detection. We used it to investigate the overlap of the detected mTPs with predicted and validated mTPs from 11 different databases. Results show that there is no clear best strategy for mTP detection applicable to all situations. We therefore propose the integration of the results of the different strategies by selecting the one with the highest odds ratio for each miRNA, as the optimal way to integrate the results. We applied this selection-integration method to the datasets and showed it to be robust to changes in the predicted and validated mTP databases. Our findings have important implications for miRNA analysis. coRmiT is implemented as part of the ExpHunterSuite Bioconductor package available from https://bioconductor.org/packages/ExpHunterSuite.
Subject(s)
MicroRNAs , Consensus , Databases, Factual , MicroRNAs/genetics , Odds Ratio , RNA-SeqABSTRACT
Cardiovascular function monitoring has been suggested as a key parameter to determine patient stability during the anesthetic process. However, the use of pulse co-oximetry has been suggested as a technology to complement the monitoring of this system as a direct way to assess hemoglobin (Hb) blood concentration. Therefore, this study aimed to correlate and determine the measurement bias between Hb blood levels with continuously determined blood hemoglobin concentration (SpHb) and arterial oxygen content values (SpOC), both obtained by noninvasive co-oximetry in dogs undergoing elective ovariohysterectomy (OVH). A total of 85 clinically healthy bitches of different breeds that were admitted for elective OVH surgery were evaluated. These animals underwent SpHb and SpOC capture after the in vivo setting for the duration of the surgical procedure. Likewise, five minutes before the end of the surgical procedure, a blood sample was obtained directly from the jugular vein to determine the blood concentration of Hb (HbLAB). The Bland-Altman analysis showed 95% limits of agreement from -4.22 to 4.99 g/dL with a BIAS (mean difference) of 0.384 ± 2.35 g/dL (r = 0.401). SpHb recordings were correlated with oxygen saturation (SpO2) (r = 0.995), SpOC (r = 0.992) and with perfusion index (PI) (r = 0.418). Therefore, SpHb presents a moderate positive correlation with direct blood concentration of Hb. This possibly shows that continuous measurement of SpHb by noninvasive co-oximetry is a reliable and advanced alternative for monitoring Hb concentration in dogs under anesthesia.
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Purpose: To compare the clinical and hormonal characteristics of patients with familial hyperaldosteronism (FH) and sporadic primary aldosteronism (PA). Methods: A systematic review of the literature was performed for the identification of FH patients. The SPAIN-ALDO registry cohort of patients with no suspicion of FH was chosen as the comparator group (sporadic group). Results: A total of 360 FH (246 FH type I, 73 type II, 29 type III, and 12 type IV) cases and 830 sporadic PA patients were included. Patients with FH-I were younger than sporadic cases, and women were more commonly affected (P = 0.003). In addition, the plasma aldosterone concentration (PAC) was lower, plasma renin activity (PRA) higher, and hypokalemia (P < 0.001) less frequent than in sporadic cases. Except for a younger age (P < 0.001) and higher diastolic blood pressure (P = 0.006), the clinical and hormonal profiles of FH-II and sporadic cases were similar. FH-III had a distinct phenotype, with higher PAC and higher frequency of hypokalemia (P < 0.001), and presented 45 years before sporadic cases. Nevertheless, the clinical and hormonal phenotypes of FH-IV and sporadic cases were similar, with the former being younger and having lower serum potassium levels. Conclusion: In addition to being younger and having a family history of PA, FH-I and III share other typical characteristics. In this regard, FH-I is characterized by a low prevalence of hypokalemia and FH-III by a severe aldosterone excess causing hypokalemia in more than 85% of patients. The clinical and hormonal phenotype of type II and IV is similar to the sporadic cases.
Subject(s)
Hyperaldosteronism , Hypokalemia , Female , Humans , Aldosterone , Hyperaldosteronism/complications , Hyperaldosteronism/genetics , Hyperaldosteronism/epidemiology , Hypokalemia/etiology , PotassiumABSTRACT
Monocyte-derived macrophages play a key pathogenic role in inflammatory diseases. In the case of rheumatoid arthritis (RA), the presence of specific synovial tissue-infiltrating macrophage subsets is associated with either active disease or inflammation resolution. JAK inhibitors (JAKi) are the first targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) approved for treatment of RA with comparable efficacy to biologics. However, the effects of JAKi on macrophage specification and differentiation are currently unknown. We have analyzed the transcriptional and functional effects of JAKi on human peripheral blood monocyte subsets from RA patients and on the differentiation of monocyte-derived macrophages promoted by granulocyte-macrophage colony-stimulating factor (GM-CSF), a factor that drives the development and pathogenesis of RA. We now report that JAKi Upadacitinib restores the balance of peripheral blood monocyte subsets in RA patients and skewed macrophages towards the acquisition of an anti-inflammatory transcriptional and functional profile in a dose-dependent manner. Upadacitinib-treated macrophages showed a strong positive enrichment of the genes that define synovial macrophages associated to homeostasis/inflammation resolution. Specifically, Upadacitinib-treated macrophages exhibited significantly elevated expression of MAFB and MAFB-regulated genes, elevated inhibitory phosphorylation of GSK3ß, and higher phagocytic activity and showed an anti-inflammatory cytokine profile upon activation by pathogenic stimuli. These outcomes were also shared by macrophages exposed to other JAKi (baricitinib, tofacitinib), but not in the presence of the TYK2 inhibitor deucravacitinib. As a whole, our results indicate that JAKi promote macrophage re-programming towards the acquisition of a more anti-inflammatory/pro-resolution profile, an effect that correlates with the ability of JAKi to enhance MAFB expression.
Subject(s)
Arthritis, Rheumatoid , Janus Kinase Inhibitors , Humans , Janus Kinase Inhibitors/pharmacology , Janus Kinase Inhibitors/metabolism , Janus Kinase Inhibitors/therapeutic use , Macrophages/metabolism , Arthritis, Rheumatoid/pathology , Inflammation/drug therapy , Inflammation/metabolism , Anti-Inflammatory Agents/metabolism , MafB Transcription Factor/genetics , MafB Transcription Factor/metabolismABSTRACT
INTRODUCTION: Primary aldosteronism (PA) is associated with several cardiometabolic comorbidities. Specific treatment by mineralocorticoid receptor antagonists (MRA) or adrenalectomy has been reported to reduce the cardiometabolic risk. However, the cardiovascular benefit could depend on plasma renin levels in patients on MRA. AIM: To compare the development of cardiovascular, renal and metabolic complications between medically treated patients with PA and those who underwent adrenalectomy, taking the renin status during MRA treatment into account. METHODS: A multicenter retrospective study (SPAIN-ALDO Register) of patients with PA treated at 35 Spanish tertiary hospitals. Patients on MRA were divided into two groups based on renin suppression (n = 90) or non-suppression (n = 70). Both groups were also compared to unilateral PA patients (n = 275) who achieved biochemical cure with adrenalectomy. RESULTS: Adrenalectomized patients were younger, had higher plasma aldosterone concentration, and lower potassium levels than MRA group. Patients on MRA had similar baseline characteristics when stratified into treatment groups with suppressed and unsuppressed renin. 97 (55.1%) of 176 patients without comorbidities at diagnosis, developed at least one comorbidity during follow-up (median 12 months vs. 12.5 months' follow-up after starting MRA and surgery, respectively). Surgery group had a lower risk of developing new cardiovascular events (HR 0.40 [95% CI 0.18-0.90]) than MRA group. Surgical treatment improved glycemic and blood pressure control, increased serum potassium levels, and required fewer antihypertensive drugs than medical treatment. However, there were no differences in the cardiometabolic profile or the incidence of new comorbidities between the groups with suppressed and unsuppressed renin levels (HR 0.95 [95% CI 0.52-1.73]). CONCLUSION: Cardiovascular, renal, and metabolic events were comparable in MRA patients with unsuppressed and suppressed renin. Effective surgical treatment of PA was associated with a decreased incidence of new cardiovascular events when compared to MRA therapy.
Subject(s)
Cardiovascular Diseases , Hyperaldosteronism , Hypertension , Humans , Adrenalectomy , Aldosterone , Biomarkers , Cardiovascular Diseases/drug therapy , Hyperaldosteronism/diagnosis , Hyperaldosteronism/drug therapy , Hyperaldosteronism/epidemiology , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiology , Mineralocorticoid Receptor Antagonists/pharmacology , Mineralocorticoid Receptor Antagonists/therapeutic use , Potassium/metabolism , Registries , Renin/metabolism , Retrospective Studies , Spain/epidemiologyABSTRACT
The present work investigates the nutritional and bioactive composition, as well as the organoleptic and sensory properties, of S. oleraceus and S. tenerrimus, two wild plant species traditionally used in the gastronomy of the Mediterranean area. Additionally, the effect of cultivation on leaf composition was assessed to explore their potential for large-scale production and commercialization from the point of view of possible losses or gains in quality. Both species were characterized as a good source of bioactive compounds, such as vitamins, pro-vitamins and carotenoids, with health-promoting and antioxidant properties that are highly appreciated. The sensory profile revealed a good general acceptance of S. oleraceus and S. tenerrimus, indicating that they could be included in the diet. Although the cultivation of S. oleraceus resulted in a decrease in the concentration of phenolic compounds when compared to wild-harvested plants, the opposite occurred for vitamin C. In S. tenerrimus, cultivation also increased the concentration of other compounds with important nutritional and healthy properties, such as sugars, organic acids and ß-carotene. The results of the composition, organoleptic and sensory properties of S. oleraceus and S. tenerrimus support the idea of their potential to be used as edible leafy vegetables and as promising assets for functional foods.
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OBJECTIVES: This study evaluated the difference in appropriateness of antimicrobial selection in pediatric patients with febrile neutropenia (FN) after implementation of an institutional guideline, a dedicated pediatric emergency medicine (EM) pharmacist, and an electronic order set. METHODS: This was a retrospective cohort study that included febrile patients aged younger than 18 years who were at risk of neutropenia, as defined by our institutional algorithm. Charts were evaluated for inclusion by searching for patients who presented to the emergency department (ED) between February 2018 and January 2022 who had International Classification of Diseases, Tenth Revision (ICD-10) codes for patients at risk of FN. Three independent groups were compared before, during, and after interventions. A historical control group (group 1), postdedicated EM pharmacist and institutional guideline cohort (group 2), and postdedicated EM pharmacist, institutional guideline, and electronic order set cohort (group 3) were compared. Secondary outcomes included time from registration in the ED to administration of the first dose of empiric antimicrobials, days to defervescence, pediatric intensive care unit length of stay, and hospital length of stay. RESULTS: Seventy-eight charts were reviewed for inclusion. Among those included (n = 38), there was an increase in appropriate use of antimicrobials from 71% to 92% to 100% ( P = 0.1534) between group 1, group 2, and group 3, respectively. In addition, the interventions in this study lead to an overall decrease in the median time from registration to first dose of antibiotics from 142 minutes to 72 minutes ( P = 0.1370). CONCLUSIONS: This study demonstrated the positive impact a pediatric EM pharmacist along with an institutional guideline and an electronic order set have on appropriate antimicrobial selection in pediatric FN patients. Institutions should consider multipronged approaches to improve the selection and time to administration of appropriate empiric antimicrobials in the ED.
Subject(s)
Anti-Infective Agents , Febrile Neutropenia , Pediatric Emergency Medicine , Humans , Child , Aged , Retrospective Studies , Pharmacists , Anti-Bacterial Agents/therapeutic use , Emergency Service, Hospital , Febrile Neutropenia/drug therapyABSTRACT
PURPOSE: To evaluate whether the clinical, biochemical and radiological features of patients with primary aldosteronism (PA) can predict both main subtypes of PA. METHODS: A retrospective multicenter study of PA patients followed in 27 Spanish tertiary hospitals (SPAIN-ALDO Register). Only patients with confirmed unilateral or bilateral PA based on adrenal venous sampling (AVS) and/or postsurgical biochemical cure after adrenalectomy were included. Supervised regression techniques were used for model development. RESULTS: 328 patients [270 unilateral PA (UPA), 58 bilateral PA (BPA)] were included. The area under the curve (AUC) for aldosterone/potassium ratio and aldosterone responses following saline infusion test were 0.602 [95%CI 0.520 to 0.684] and 0.574 [95% CI 0.446-0.701], respectively, to differentiate UPA from BPA. The AUC was 0.825 [95% 0.764-0.886] when the prediction model with seven parameters - comorbidities (dyslipidemia, cerebrovascular disease, sleep apnea syndrome [SAS]), systolic blood pressure (SBP), plasma aldosterone levels (PAC), hypokalemia and unilateral adrenal nodule >1 cm and normal contralateral adrenal gland on CT/MRI - was used. In patients without comorbidities, hypokalemia, SBP > 160 mmHg, PAC > 40 ng/dL, and unilateral adrenal lesions were associated with a likelihood of having a UPA of 98.5%. The chance of BPA was higher in individuals with comorbidities, SBP < 140 mmHg, normokalemia, low PAC levels, and no adrenal tumors on the CT/MRI (91.5%). CONCLUSION: A combination of high PAC, SBP > 160 mmHg, low serum potassium, a unilateral adrenal nodule>1 cm and no comorbidities could predict a UPA with a 98.5% accuracy.
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AIM: To analyze differences in ventilatory parameters and outcome with different ventilatory methods during CPR. METHODS: Pragmatic prospective quasi-experimental study in out-of-hospital urban environment. Patients over 18 years of age in non-traumatic cardiac arrest, attended by an emergency medical service between April 2021 and September 2022, were included. Two groups were compared according to the ventilatory method: mechanical ventilator (IPPV, tidal volume 7 ml/kg, frequency 10-12 bpm) or manual resuscitator bag. The main variables of interest are those of gasometry performed 15 minutes after intubation or when spontaneous circulation is recovered and final outcome. Patients were followed up to hospital discharge. RESULTS: Of the 359 patients attended, 150 were included (71 in IPPV and 79 with a bag). In patients with arterial blood gases, pCO2 was 67.8 ± 21.1 in the IPPV group vs 95.9 ± 39.0 mmHg in the bag group (p = 0.006) and pH was 7.00 ± 0.18 vs 6.92 ± 0.18 (p = 0.18). With a venous sample, the pCO2 was 68.1 ± 18.9 vs 89.5 ± 26.5 mmHg (p < 0.001) and the pH was 7.03 ± 0.15 vs 6.94 ± 0.17 (p = 0.005), respectively. Survival with CPC 1-2 to hospital discharge was 15.6% with IPPV and 11.3% with bag (p = 0.44). CONCLUSION: The use of a mechanical ventilator in IPPV was associated with a better ventilatory status during CPR compared to the use of the bag, without conclusive data regarding its clinical repercussion with the sample collected.
Subject(s)
Cardiopulmonary Resuscitation , Emergency Medical Services , Out-of-Hospital Cardiac Arrest , Humans , Adolescent , Adult , Out-of-Hospital Cardiac Arrest/therapy , Prospective Studies , Cardiopulmonary Resuscitation/methods , Emergency Medical Services/methods , Ventilators, MechanicalABSTRACT
Grain mold and stalk rot are among the fungal diseases that cause significant losses in sorghum worldwide and are caused by different Fusarium spp. The presence of Fusarium species in sorghum grains causes yield losses and mycotoxin contamination, which represents a risk to consumers. In this study, Fusarium graminearum species complex (FGSC) had a high incidence, followed by Fusarium fujikuroi species complex (FFSC) and F. incarnatum-equiseti species complex. Within FFSC, F. proliferatum, F. andiyazi, F. fujikuroi, F. thapsinum, F. verticillioides and F. subglutinans were identified, and this was the first report of F. fujikuroi in sorghum. The most frequent toxins found in sorghum samples were deoxynivalenol (DON) and zearalenone (ZEN). The presence of fumonisins and nivalenol (NIV) was detected at low levels. This study adds new knowledge about the occurrence of Fusarium species and mycotoxins in sorghum grains. Furthermore, this is the first report in Uruguay on fungicide sensitivity for Fusarium isolates from sorghum, which constitutes an important starting point for defining management practices to minimize fungal infection and mycotoxin contamination.
Subject(s)
Fumonisins , Fusarium , Mycotoxins , Sorghum , Uruguay , Edible GrainABSTRACT
Purpose: The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes. Methods: This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 µg/dL (confirmed ACS if >5 µg/dL and possible ACS if 1.8-5 µg/dL) in the absence of specific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels. Results: The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS-PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS-PA and PA-only patients was similar, except for older age and larger tumor size of the adrenal lesion in the ACS-PA group. When comparing the ACS-PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64-22.32)) and cardiovascular events (OR 5.0 (2.29-11.07)) was higher in ACS-PA patients than in ACS patients. The coexistence of ACS in patients with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS-PA and PA-only groups. Conclusion: Co-secretion of cortisol and aldosterone affects almost one-third of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS-PA and PA-only are similar.
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Food represents the major risk factor for exposure to mercury in most human populations. Therefore, passage through the gastrointestinal tract plays a fundamental role in its entry into the organism. Despite the intense research carried out on the toxicity of Hg, the effects at the intestinal level have received increased attention only recently. In this review we first provide a critical appraisal of the recent advances on the toxic effects of Hg at the intestinal epithelium. Next, dietary strategies aimed to diminish Hg bioavailability or modulate the epithelial and microbiota responses will be revised. Food components and additives, including probiotics, will be considered. Finally, limitations of current approaches to tackle this problem and future lines of research will be discussed.
Subject(s)
Mercury , Humans , Mercury/toxicity , Mercury/analysis , Dietary Exposure/adverse effects , Intestines , Diet , Gastrointestinal TractABSTRACT
INTRODUCTION: Traumatic brain injury (TBI) is a public health concern with limited treatment options because it causes a cascade of side effects that are the leading cause of hospital death. Thioredoxin is an enzyme with neuroprotective properties such as antioxidant, antiapoptotic, immune response modulator, and neurogenic, among others; it has been considered a therapeutic target for treating many disorders. METHODS: The controlled cortical impact (CCI) model was used to assess the effect of recombinant human thioredoxin 1 (rhTrx1) (1 µg/2 µL, intracortical) on rats subjected to TBI at two different times of the light-dark cycle (01:00 and 13:00 h). We analyzed the food intake, body weight loss, motor coordination, pain perception, and histology in specific hippocampus (CA1, CA2, CA3, and Dental Gyrus) and striatum (caudate-putamen) areas. RESULTS: Body weight loss, reduced food intake, spontaneous pain, motor impairment, and neuronal damage in specific hippocampus and striatum regions are more evident in rats subjected to TBI in the light phase than in the dark phase of the cycle and in groups that did not receive rhTrx1 or minocycline (as positive control). Three days after TBI, there is a recovery in body weight, food intake, motor impairment, and pain, which is more pronounced in the rats subjected to TBI at the dark phase of the cycle and those that received rhTrx1 or minocycline. CONCLUSIONS: Knowing the time of day a TBI occurs in connection to the neuroprotective mechanisms of the immune response in diurnal variation and the usage of the Trx1 protein might have a beneficial therapeutic impact in promoting quick recovery after a TBI.
Subject(s)
Brain Injuries, Traumatic , Neuroprotective Agents , Humans , Rats , Animals , Minocycline/therapeutic use , Brain Injuries, Traumatic/metabolism , Hippocampus/metabolism , Thioredoxins/pharmacology , Thioredoxins/metabolism , Thioredoxins/therapeutic use , Weight Loss , Neuroprotective Agents/therapeutic use , Disease Models, AnimalABSTRACT
In animals with chronic pathologies, the detection of proteinuria via the proteinuria: creatininuria ratio (UPC) and urinary protein electrophoresis allows for the early diagnosis of chronic kidney disease (CKD). The objective of this work was to identify and determine the magnitude of proteinuria and its electrophoretic pattern characterization in dogs with chronic diseases pathophysiologically related to proteinuria. With the studied patients, five groups were formed. The control group (CG) contained non-proteinuric cases. The cases with proteinuria were classified into four groups according to the concurrent disease: chronic inflammatory diseases (IG), neoplasms (NG), heart diseases (HG), and endocrine diseases (EG). For the statistical analysis, descriptive statistics and non-parametric tests were used. Data from 264 dogs were obtained; in the disease groups, proteinuria was observed in more than 30% as the only finding of kidney disease, evidencing a greater risk factor for proteinuria in the HG group (OR 4.047, CI 1.894-8.644, p < 0.0001). In the HG, NG, and EG groups, a higher frequency of glomerular pattern (GEP) related to glomerular hypertension was observed; in the IG, a higher frequency of mixed pattern (MEP) was observed. These findings are secondary to the hyperfiltration process that affects the glomerulus and the renal tubule.
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Introduction: Cigarette smoking adversely affects multiple aspects of human health including eye disorders such as age-related macular degeneration, cataracts and dry eye disease. However, there remains a knowledge gap in how constituents of cigarette smoke affect vision and retinal biology. We used zebrafish to assess effects of short-term acute exposure to cigarette smoke extract (CSE) on visual behaviour and retinal biology. Methods: Zebrafish larvae with a developed visual system at three days post-fertilization (dpf) were exposed to CSE for 4, 24 or 48 hours. Visual behaviour, hyaloid vasculature morphology, retinal histology, oxidative stress gene expression and outer segment phagocytosis were investigated using visual behavioural optokinetic and visual motor response assays (OKR and VMR), microscopy (light, fluorescence and transmission electron microscopy), and real-time PCR. Results: In zebrafish larvae, 48 hours of CSE treatment resulted in significantly reduced visual behaviour. Larvae treated with 10, 15 or 20 µg/mL CSE showed an average of 13.7, 10.7 or 9.4 saccades per minute, respectively, significantly lower compared with 0.05% DMSO controls (p=0.0093, p=0.0004 and p<0.0001, respectively) that exhibited 19.7 saccades per minute. The diameter of intraocular vessels increased from 4.833 µm in 0.05% DMSO controls to 5.885 µm in the 20 µg/mL CSE-treated larvae (p=0.0333). Biometry analysis highlighted a significant axial length elongation in 20 µg/mL CSE-treated larvae (216.9 µm, p<0.0001) compared to 0.05% dimethyl sulfoxide (DMSO) controls (205.1 µm). Larvae exposed to 20 µg/mL CSE had significantly (p=0.0002) higher numbers of RPE phagosomes compared to vehicle controls (0.1425 and 0.093 phagosomes/µm RPE, respectively). Conclusions: Zebrafish larvae with a developed visual system display apparent defects in visual behaviour and retinal biology after acute exposure to CSE, establishing a valuable in vivo model to investigate ocular disorders related to cigarette smoke.
This study investigates the effects of cigarette smoke on the visual system of zebrafish larvae. We exposed the larvae to cigarette smoke extract for 4, 24, or 48 hours and assessed their eye movements, retina morphology and oxidative stress gene expression. Exposure to cigarette smoke extract for 48 hours reduced eye movements behaviour in the zebrafish larvae and led to changes in the morphology of their hyaloid vasculature present in the lens and the number of phagosomes in their retinal pigment epithelium. When exposure was shortened to 4 or 24 hours, eye movements were still reduced and oxidative stress was affected. These results suggest that zebrafish larvae can be used as a valuable model to investigate ocular disorders related to cigarette smoke.