How ChatGPT performs in Oral Medicine: The case of oral potentially malignant disorders

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Time course of brain oxidative damage caused by intrastriatal administration of 6-hydroxydopamine in a rat model of Parkinson’s disease

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s11064-006-9232-6The unilateral and intrastriatal injection of 6-hydroxydopamine is commonly used to provide a partial lesion model of Parkinson’s disease in the investigation of the molecular mechanisms involved in its pathogenesis and to assess new neuroprotective treatments. Its capacity to induce neurodegeneration has been related to its ability to undergo autoxidation in the presence of oxygen and consequently to generate oxidative stress. The aim of the present study was to investigate the time course of brain oxidative damage induced by 6-hydroxydopamine (6 μg in 5 μl of sterile saline containing 0.2% ascorbic acid) injection in the right striatum of the rat. The results of this study show that the indices of both lipid peroxidation (TBARS) and protein oxidation (carbonyl and free thiol contents) increase simultaneously in the ipsilateral striatum and ventral midbrain, reaching a peak value at 48-h post-injection for both TBARS and protein carbonyl content, and at 24 h for protein free thiol content. A lower but significant increase was also observed in the contralateral side (striatum and ventral midbrain). The indices of oxidative stress returned to values close to those found in controls at 7-day post-injection. These data show that the oxidative stress is a possible triggering factor for the neurodegenerative process and the retrograde neurodegeneration observed after 1-week post-injection is a consequence of the cell damage caused during the first days post-injection. The optimal time to assess brain indices of oxidative stress in this model is 48-h post-injection.This study was supported by Grant BFI2003-00493 from the Ministerio de Ciencia y Tecnología with the contribution of the European Regional Development Found (Madrid, Spain) and Grant PGDIT03PXIB20804PR from the Xunta de Galicia (Santiago de Compostela, Spain).S

Angiotensin type-1-receptor antagonists reduce 6-hydroxydopamine toxicity for dopaminergic neurons

Angiotensin II activates (via type 1 receptors) NAD(P)H-dependent oxidases, which are a major source of superoxide, and is relevant in the pathogenesis of several cardiovascular diseases and certain degenerative changes associated with ageing. Given that there is a brain renin–angiotensin system and that oxidative stress is a key contributor to Parkinson's disease, we investigated the effects of angiotensin II and angiotensin type 1 (AT1) receptor antagonists in the 6-hydroxydopamine model of Parkinson's disease. Rats subjected to intraventricular injection of 6-hydroxydopamine showed bilateral reduction in the number of dopaminergic neurons and terminals. Injection of angiotensin alone did not induce any significant effect. However, angiotensin increased the toxic effect of 6-hydroxydopamine. Rats treated with the AT1 receptor antagonist ZD 7155 and then 6-hydroxydopamine (with or without exogenous administration of angiotensin) showed a significant reduction in 6-hydroxydopamine-induced oxidative stress (lipid peroxidation and protein oxidation) and dopaminergic degeneration. Dopaminergic degeneration was also reduced by the NAD(P)H inhibitor apocynin. Angiotensin may play a pivotal role, via AT1 receptors, in increasing the oxidative damage of dopaminergic cells, and treatment with AT1 antagonists may reduce the progression of Parkinson's disease.S

Risk of Acute Myocardial Infarction Among New Users of Allopurinol According to Serum Urate Level: A Nested Case-Control Study

Abstract: Objectives: To test the hypothesis that allopurinol reduces the risk of acute myocardial infarction (AMI) in hyperuricemic patients and to assess whether the effect is dependent on dose, duration and serum uric acid (SUA) level attained after treatment. Methods: Nested case-control study over the period 2002?2015. From a cohort of patients aged 40?99 years old, we identified incident AMI cases and randomly selected five controls per case, matched for exact age, sex and index date. Adjusted odds ratios (AOR) and 95% CI were computed through unconditional logistic regression. Only new users of allopurinol were considered. Results: A total of 4697 AMI cases and 18,919 controls were included. Allopurinol use was associated with a reduced risk of AMI mainly driven by duration of treatment (AOR ?180 days = 0.71; 95% CI: 0.60?0.84). Among long-term users (>180 days), the reduced risk was only observed when the SUA level attained was below 7 mg/dL (AOR7mg/dL = 1.04; 95% CI: 0.75?1.46; p for trend = 0.001). A dose-effect was observed but faded out once adjusted for the SUA level attained. The reduced risk of AMI occurred in both patients with gout and patients with asymptomatic hyperuricemia. Conclusions: The results confirm a cardioprotective effect of allopurinol which is strongly dependent on duration and SUA level attained after treatment

Long-term cardiac reverse remodeling after cardiac resynchronization therapy

Introduction: The benefit of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF) have been observed in the first year. However, there are few data on long-term follow-up and the effect of changes of LVEF on mortality. This study aimed to assess the LV remodeling after CRT implantation and the probable effect of changes in LVEF with repeated measures on mortality over time in a real-world registry. Methods: Among our cohort of 328 consecutive CRT patients, mixed model effect analysis have been made to describe the temporal evolution of LVEF and LVESV changes over time up with several explanatory variables. Besides, the effect of LVEF along time on the probability of mortality was evaluated using joint modeling for longitudinal and survival data. Results: The study population included 328 patients (253 men; 70.2 ± 9.5 years) in 4.2 (2.9) years follow-up. There was an increase in LVEF of 11% and a reduction in LVESV of 42 mL during the first year. These changes are more important during the first year, but slight changes remain during the follow-up. The largest reduction in LVESV occurred in patients with left bundle branch block (LBBB) and the smallest reduction in patients with NYHA IV. The smallest increase in LVEF was an ischemic etiology, longer QRS, and LV electrode in a nonlateral vein. Besides, the results showed that the LVEF profiles taken during follow-up after CRT were associated with changes in the risk of death. Conclusion: Reverse remodeling of the left ventricle is observed especially during the first year, but it seems to be maintained later after CRT implantation in a contemporary cohort of patients. Longitudinal measurements could give us additional information at predicting the individual mortality risk after adjusting by age and sex compared to a single LVEF measurement after CRTS

Association of oral bisphosphonates with cardioembolic ischemic stroke: a nested case-control study

Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and noncardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants. Methods: We performed a case-control study nested in a cohort of patients aged 40?99 years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered. Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01?1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10?1.66) and 1.03 (95% CI: 0.88?1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR?1 year = 1.10; 95% CI:0.82?1.49; AOR>1?3 years = 1.41; 95% CI: 1.01?1.97; AOR>3 years = 1.81; 95% CI:1.25?2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR>1 year = 0.59; 0.30?1.16). An interaction between oral bisphosphonates and calcium supplements was suggested. Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS.Research Foundation of the University Hospital Príncipe de Asturia

Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study

Conventional chemotherapy against colorectal cancer (CRC), the third most common cancer in the world, includes oxaliplatin (Oxa) which induces serious unwanted side effects that limit the efficiency of treatment. Therefore, alternative therapeutic approaches are urgently required. In this work, biomimetic magnetic nanoparticles (BMNPs) mediated by MamC were coupled to Oxa to evaluate the potential of the Oxa–BMNP nanoassembly for directed local delivery of the drug as a proof of concept for the future development of targeted chemotherapy against CRC. Electrostatic interactions between Oxa and BMNPs trigger the formation of the nanoassembly and keep it stable at physiological pH. When the BMNPs become neutral at acidic pH values, the Oxa is released, and such a release is greatly potentiated by hyperthermia. The coupling of the drug with the BMNPs improves its toxicity to even higher levels than the soluble drug, probably because of the fast internalization of the nanoassembly by tumor cells through endocytosis. In addition, the BMNPs are cytocompatible and non-hemolytic, providing positive feedback as a proof of concept for the nanoassembly. Our study clearly demonstrates the applicability of Oxa–BMNP in colon cancer and offers a promising nanoassembly for targeted chemotherapy against this type of tumor.This work was also supported by the Consejería de Salud de la Junta de Andalucía (projects PI-0476-2016 and PI-0102-2017). Y.J. and B.G.-P. acknowledge FPU2016 grants (FPU16_04580 and FPU16_01716, respectively) from the Ministerio de Educación, Ciencia, y Deporte y Competitividad (Spain)

Comparison of physical fitness profiles obtained before and during COVID-19 pandemic in two independent large samples of children and adolescents: DAFIS Project

[Abstract]: COVID-19 pandemic restrictions might have negatively affected the health-related physical fitness of children and adolescents. The aim of this study was to contrast the body composition and physical fitness data of two independent samples of children and adolescents obtained from an online database (DAFIS project) before (n = 15,287) and during (n = 2101) the first academic year of the COVID-19 pandemic. The results revealed higher values for the body mass index (p = 0.002), waist circumference (p 0.05). Our data suggested that pandemic constraints might have affected body composition and muscular fitness of children and adolescents. These results might be of interest for designing specific interventions oriented toward counteracting the negative effects of pandemic restrictions on health-related physical fitness

Percentiles and Principal Component Analysis of Physical Fitness From a Big Sample of Children and Adolescents Aged 6-18 Years: The DAFIS Project

[Abstract] Assessing physical fitness has emerged as a proxy of the health status of children and adolescents and therefore as relevant from a public health point of view. DAFIS is a project included in Plan Galicia Saudable (Healthy Galicia Plan) of the regional government of Galicia (Spain). DAFIS consists of an on-line software devoted to record the results of a standard physical fitness protocol carried out as a part of the physical education curriculum. The aims of this study were: to obtain normative values of physical fitness of the Galician school population evaluated in the DAFIS project, and to identify a reduced number of components and tests able to capture a significant amount of the variability in the physical fitness of children and adolescents. From an initial sample of 27784 records, 15287 cases (7543 males, 7744 females) were considered after filtering. Generalized Additive Models for Location, Scale and Shape were used for obtaining percentile curves and tables for each sex. Furthermore, a principal components analysis was performed, selecting the number of components by applying the Kaiser’s rule and selecting a subset of variables considering the correlation between each variable and the components. Percentile curves and normative values are reported for each test and sex. Physical fitness was better in boys than in girls throughout age groups, except for flexibility that was consistently higher in girls. Two main components were detected throughout age groups: the first one representing body composition and partially cardiorespiratory fitness and the second one muscular fitness. For boys and girls, waist to height ratio had the highest correlations with the first component in four out of six age groups. The highest correlation with the second component, was most frequently observed for the handgrip test both in boys and girls (four out of six age groups). This study provides evidence about the utility of school community actions like DAFIS aimed to track the health-related fitness of children and adolescents. The results suggest that fat mass distribution (i.e., waist to height ratio and waist circumference) and muscular performance (mainly handgrip) concentrate a high proportion physical fitness variance