12 research outputs found
Perception of dentists, dental students, and patients on dentogingival aesthetics
No full textAbstract Introduction Patients’ demand for dentogingival aesthetics has increased significantly in recent years, and this is a complex concept due to numerous factors involved in obtaining patient/professional satisfaction. Some dentogingival features may alter smile harmony, such as excessive gingival display. Objective To evaluate whether the presence of gingival display has a negative influence on the perception of dentogingival aesthetics. Material and method 180 individuals (60 dentists, 60 dental students, and 60 patients) evaluated images of volunteer smiles. These images were digitally altered by the Adobe Photoshop™ software, creating different situations of gingival display (4 mm, 2 mm, 0 mm, -2 mm, -4 mm), and graded by the evaluators with the following scores: (01) very pleasant smile, (02) pleasant smile, and 03) unpleasant smile. The scores assigned were analyzed using ANOVA (α=0.05). Result Gingival displays between 0 and 2 mm were considered aesthetically pleasing. Changes of -4 and +4 mm were defined as the most disharmonious smiles. The 0-mm female smile was considered the most harmonious for dentists (1.51) and dental students (1.77), by Student's t test (p<0.05). In the opinion of patients, the smile of +2 mm was considered the most aesthetic. In the image evaluations of men, the 0-mm smile was considered the most aesthetic (p <0.05) for dentists (1.85) and dental students (1.62). The patients considered +2 mm of gingival display the most harmonious smile. Conclusion The aesthetic perception of dental students and dentists was different when compared to the group of patients
Perception of dentists, dental students, and patients on dentogingival aesthetics
No full textAbstract Introduction Patients’ demand for dentogingival aesthetics has increased significantly in recent years, and this is a complex concept due to numerous factors involved in obtaining patient/professional satisfaction. Some dentogingival features may alter smile harmony, such as excessive gingival display. Objective To evaluate whether the presence of gingival display has a negative influence on the perception of dentogingival aesthetics. Material and method 180 individuals (60 dentists, 60 dental students, and 60 patients) evaluated images of volunteer smiles. These images were digitally altered by the Adobe Photoshop™ software, creating different situations of gingival display (4 mm, 2 mm, 0 mm, -2 mm, -4 mm), and graded by the evaluators with the following scores: (01) very pleasant smile, (02) pleasant smile, and 03) unpleasant smile. The scores assigned were analyzed using ANOVA (α=0.05). Result Gingival displays between 0 and 2 mm were considered aesthetically pleasing. Changes of -4 and +4 mm were defined as the most disharmonious smiles. The 0-mm female smile was considered the most harmonious for dentists (1.51) and dental students (1.77), by Student's t test (p</div
Contribuições da liga de nutrologia para a formação acadêmica dos alunos de medicina da Universidade Federal do Rio Grande do Sul
No full textTargeting RTK signaling pathways in cancer
No full textThe RAS/MAP kinase and the RAS/PI3K/AKT pathways play a key role in the regulation of proliferation, differentiation and survival. The induction of these pathways depends on Receptor Tyrosine Kinases (RTKs) that are activated upon ligand binding. In cancer, constitutive and aberrant activations of components of those pathways result in increased proliferation, survival and metastasis. For instance, mutations affecting RTKs, Ras, B-Raf, PI3K and AKT are common in perpetuating the malignancy of several types of cancers and from different tissue origins. Therefore, these signaling pathways became prime targets for cancer therapy. This review aims to provide an overview about the most frequently encountered mutations, the pathogenesis that results from such mutations and the known therapeutic strategies developed to counteract their aberrant functions
The polyphenols resveratrol and caffeic acid phenethyl ester: their influence on growth-related signaling pathways in vascular smooth muscle cells
No full textmTOR complex 2 - akt signaling is physically and functionally at mam
No full textThe target of rapamycin (TOR) is a conserved protein kinase and a
central controller of growth. TOR can be part of two structurally and
functionally distinct complexes, termed TOR complex 1 and TOR
complex 2. Mammalian TOR complex 2 (mTORC2) is composed of
mTOR, Rictor, Sin1 and mLST8. Both mTORC1 and mTORC2 are activated
by growth factors. The mechanism via which growth factors
regulate mTORC2 has been elusive until recently. mTORC2 binds ribosomes
in a growth factor stimulated manner and this association is
required for mTORC2 activity.
mTOR complex 2 functions include control of spatial cell growth
and metabolism and thus, mTORC2 deregulation has been linked
to various disorders including cancer and diabetes. mTORC2 phosphorylates
and thereby activates the AGC kinase family member Akt
(PKB). Akt has many different targets and functions, not all of which
depend on mTORC2 mediated Akt phosphorylation.
In order to gain a better understanding of mTORC2 function, we
asked where mTORC2 signaling is localized. A number of studies
localized mTORC2, functionally or physically, either to the endoplasmic
reticulum (ER) or to mitochondria.We investigated whether these
seemingly unrelated observations concerning mTORC2 localization,
might be the consequence of mTORC2 signaling at MAM. MAM
or mitochondria-associated ER membrane is a quasi-synaptic subdomain
between the ER and mitochondria. MAM plays a crucial role in
the regulation of mitochondrial metabolism and cell survival by gating
both the calcium flux and phospholipid trafficking between the
ER and mitochondria.
First, we analyzed mTORC2 subcellular localization. mTORC2 is
localized to the ER adjacent to mitochondria and mTORC2 can be
biochemically isolated from MAM structures. mTOR complex 2 interacts
with the IP3R-Grp75-VDAC1 complex, a tether that connects ER
and mitochondria at MAM. Insulin stimulates mTORC2 localization
to MAM and mTORC2 interaction with the IP3R-Grp75-VDAC1 complex.
MAM localization of mTORC2 depends on mTORC2-ribosome
interaction.
Next we investigated the function of mTORC2 at MAM. Rictor
(mTORC2) knockout causes a decrease in MAM formation. Growth
factors stimulate MAM formation via mTORC2 and the Akt substrate
PACS2, a MAM resident protein. As expected for MAM deficient
cells, mTORC2 disruption changes the calcium flux from the ER to
mitochondria at MAM. Furthermore, we observe a reduction of Akt
mediated phosphorylation of the MAM calcium channel IP3R upon
Rictor knockout. Thus, mTORC2 signaling at MAM controls MAM mediated
calcium release via the Akt targets PACS2 and IP3R.
Since MAM disruption and calcium signaling both affect mitochondrial
metabolism, we proceeded by analyzing the mitochondrial physiology
of mTORC2 deficient cells. Rictor knockout cells exhibit a disruption
of VDAC1-HK2 binding, caused by a lack of Akt mediated
phosphorylation of HK2 at MAM. This, together with the defect in
MAM, induces an increase in basal respiration, mitochondrial inner
membrane potential, and ATP production in the mTORC2 deficient
cells, culminating in apoptosis. Thus, mTORC2 at MAM appears to
control several aspects of mitochondrial physiology.
These findings emphasize the role of MAM as a signaling hub that
controls cell physiology. By identifying the integral role of mTORC2
at the core of this platform, our results provide new insights on
the mechanisms that regulate growth and metabolism. These observations
may offer new therapeutic strategies against mTORC2 and
MAM driven diseases such as diabetes, Alzheimer’s and cancer
Divergence Between Clinical Trial Evidence and Actual Practice in Use of Dual Antiplatelet Therapy After Transient Ischemic Attack and Minor Stroke
No full textBackground: Randomized controlled trials (RCTs) proved that short-term (21-90 days) dual antiplatelet therapy (DAPT) reduces the risk of early ischemic recurrences after a noncardioembolic minor stroke or high-risk transient ischemic attack (TIA) without substantially increasing the hemorrhagic risk. We aimed at understanding whether and how real-world use of DAPT differs from RCTs.Methods: READAPT (Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or TIA) is a prospective cohort study including >18-year-old patients treated with DAPT after a noncardioembolic minor ischemic stroke or high-risk TIA from 51 Italian centers. The study comprises a 90-day follow-up from symptom onset. In the present work, we reported descriptive statistics of baseline data of patients recruited up to July 31, 2022, and proportions of patients who would have been excluded from RCTs. We compared categorical data through the ?(2) test.Results: We evaluated 1070 patients, who had 72 (interquartile range, 62-79) years median age, were mostly Caucasian (1045; 97.7%), and were men (711; 66.4%). Among the 726 (67.9%) patients with ischemic stroke, 226 (31.1%) did not meet the RCT inclusion criteria because of National Institutes of Health Stroke Scale score >3 and 50 (6.9%) because of National Institutes of Health Stroke Scale score >5. Among the 344 (32.1%) patients with TIA, 69 (19.7%) did not meet the RCT criteria because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score <4 and 252 (74.7%) because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score <6 and no symptomatic arterial stenosis. Additionally, 144 (13.5%) patients would have been excluded because of revascularization procedures. Three hundred forty-five patients (32.2%) did not follow the RCT procedures because of late (>24 hours) DAPT initiation; 776 (72.5%) and 676 (63.2%) patients did not take loading doses of aspirin and clopidogrel, respectively. Overall, 84 (7.8%) patients met the RCT inclusion/exclusion criteria.Conclusions: The real-world use of DAPT is broader than RCTs. Most patients did not meet the RCT criteria because of the severity of ischemic stroke, lower risk of TIA, late DAPT start, or lack of antiplatelet loading dose
Embryonic stem cells: modelling effects ofearly embryo environment
No full textThe Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that embryonic environment can induce permanent changes in metabolism during development, increasing the risk of disease in adults. Adverse environments during critical stages of gestation are sufficient to induce adaptations in offspring and disease susceptibility in later life. Rodent models show that maternal diet exclusively during preimplantation development induces cardiovascular and metabolic disease in adult offspring. Changes must therefore occur within the distinct cell populations of the early embryo and be maintained throughout development. Determining adaptive mechanisms has been challenging due to the small size of the early embryo, and genetic variability in outbred strains previously used. We generated mouse embryonic stem (ES) cells from inbred C57BL/6 mice as a model to overcome these problems. These were used to characterise mechanisms associated with the embryo’s adaptive responses to maternal diet. ES cell lines were derived from blastocysts of C57BL/6 mice assigned to either an isocaloric low protein diet (LPD), or a control diet exclusively through preimplantation development. ES cell lines were characterised for karyotype, sex, gene expression, and functional characteristics including proliferation, death, and metabolism at standardised passages. LPD had no impact on blastocyst formation in vivo or blastocyst cell lineage allocation. Experimental conditions did affect blastocyst outgrowth development in vitro. LPDoutgrowths cultured with less feeder fibroblasts showed slower development than controls. Although LPD blastocyst outgrowth was comparable to controls under high feeder growth conditions, there was a significant reduction in the capacity for ES cell derivation. There was a prominent sex bias towards male ES cell lines. These ES cells retained similar levels of gene expression related to pluripotency, housekeeping and developmental functions irrespective of diet. LPD did not affect growth or metabolism. These cells however showed increased basal apoptosis, and reduced levels of phosphorylated Extracellular signal-regulated kinase (ERK). The reduced ES cell isolation efficiency may indicate a reduced number of pluripotent cells present within the early embryo or increased sensitivity of these cells in response to maternal LPD. Increased apoptosis in ES cells derived from LPD-blastocysts reveal that these cells are indeed more sensitive. Reduced activated ERK may suggest that dysregulated ERK-mediated survival signalling causes enhanced apoptosis. Such adaptations in the early embryo may impact on lineage allocation as differentiation occurs. These ES cell lines may provide a model to investigate such mechanistic adaptations in post-implantation tissues providing further insight into foetal responses to poor nutrition and the induction of adult onset disease
The use of a genetic strategy to study the role of modulation of oxidative stress by uncoupling proteins 2 and 3 in the pathogenesis of Type 2 Diabetes
No full textMitochondrial dysfunction has been implicated in the early pathogenesis of Type 2 Diabetes. The uncoupling proteins 2 and 3 are mitochondrial proteins found in man that have been implicated in protecting mammals from the effects of over-nutrition. Examination of the effect of genetic variation in the UCP2-UCP3 genetic cluster has so far been inconclusive. The aim of this thesis was to examine, using a genetic strategy, the hypothesis that the role of the uncoupling proteins 2 and 3 in the pathogenesis of Type 2 Diabetes is via modification of oxidative stress.
In a prospective study of nearly 3000 men the risk of type 2 diabetes at 10 years was increased for both the UCP2-866AA (1.94 [1.18-3.19]: p=0.009) and the UCP3-55TT (2.06 [1.06-3.99]: p=0.03) homozygotes. This increased risk was not explained by the association with any measured conventional risk factors. Paradoxically, in a Europe-wide cross-sectional study of 598 subjects the UCP2-866A variant was associated with lower waist-hip ratio (GX v AA,1.00 [0.06] v 0.98 [0.07]; p=0.003), although also associated with lower insulin secretion (42.6 [24.6] v 35.6 [18.6]; p=0.03). The UCP3 variant was not significantly associated with any metabolic trait.
The significant heritability of plasma markers of oxidative stress (TAS 0.54, TOAS 0.49) suggests anti-oxidant function is a plausible mechanism to determine Type 2 Diabetes risk. The predictors of anti-oxidant stress in a family study were examined, as was the impact of UCP2-UCP3 gene cluster variation. Genetic variation in the UCP2-UCP3 was found to increase the risk of the Type 2 diabetes. While UCP2 may modify insulin secretion directly, the mechanism of action for UCP3 is likely to involve novel risk factors for Type 2 Diabetes such as modification of mitochondrial oxidative stress. Finally, the development of a human model is described to examine genetic influences on oxidative stress burden using a meal rich in used cooking oil
ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19
No full textThe International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use
