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1.
Front Psychol ; 15: 1356642, 2024.
Article in English | MEDLINE | ID: mdl-38966746

ABSTRACT

Inclusive education involves the interaction of diverse actors from different societal sectors, such as education, health, and policy. Inclusion laws and regulations in Chile are relatively new and have been taken as a regional model. However, the efforts to implement them have revealed some structural difficulties that must be discussed. This conceptual analysis article aims to provide insights to enrich cross-sectoral collaboration to foster inclusive cultures in Chilean schools. Considering the OECD Analytical Framework, which describes a systemic approach, we provide definitions for the critical components of the model and discuss the advances and challenges of current Chilean public policies in this field -including the Chile Crece Contigo and the School Integration Programs (SIP)-, the Chilean education system functioning, the social contexts, and students' needs and supports based on the available evidence. Building from inclusive education literature and previous experiences, we delve into the model to address the needs of students with disabilities, social and cultural disadvantages, students belonging to the indigenous population, and students with a low socioeconomic level to propose action guidelines with a particular focus on integrating inclusive practices at the school level.

2.
Rev Port Cardiol ; 42(5): 445-451, 2023 05.
Article in English, Portuguese | MEDLINE | ID: mdl-36706913

ABSTRACT

INTRODUCTION: The benefit of complete revascularization (CR) on long-term total event reduction in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD), still remains unclear. We assessed the efficacy of three different revascularization strategies on long-term total recurrent events. METHODS: We retrospectively analyzed 414 consecutive patients admitted with STEMI and MVD who were categorized according to the revascularization strategy used: culprit-vessel-only percutaneous coronary intervention (PCI) (n=163); in-hospital CR (n=136); and delayed CR (n=115). The combined endpoint assessed was all-cause mortality, the total number of myocardial infarctions, ischemia-driven revascularizations or strokes. Negative binomial regression was used to assess the association between the revascularization strategy and total events; risk estimates were expressed as an incidence rates ratio (IRR). RESULTS: At a median follow-up of four years (1.2-6), rates of the combined endpoint per 10 patient-years were 18, 0.8, and 0.6 in culprit-vessel-only PCI, in-hospital CR, and delayed CR strategies, respectively (p<0.001). After multivariable adjustment and when compared with culprit-vessel-only PCI, both in-hospital and delayed CR strategies were significantly associated with a reduction in the combined endpoint (IRR=0.40: 95% confidence interval (CI), 0.25-0.64; p<0.001; and IRR 0.40: 95% CI, 0.24-0.62; p<0.001, respectively). No differences were observed across in-hospital and delayed CR strategies. CONCLUSIONS: Complete revascularization of non-culprit lesions in patients with STEMI and MVD reduces the risk of total recurrent events during long-term follow-up. No differences between in-hospital and delayed CR strategies were found.


Subject(s)
Coronary Artery Disease , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/surgery , ST Elevation Myocardial Infarction/etiology , Coronary Artery Disease/etiology , Retrospective Studies , Percutaneous Coronary Intervention/adverse effects , Myocardial Infarction/etiology , Treatment Outcome , Myocardial Revascularization
3.
Lang Speech Hear Serv Sch ; 54(1): 63-81, 2023 01 17.
Article in English | MEDLINE | ID: mdl-35985325

ABSTRACT

PURPOSE: This study aims to illustrate how environmental systems shape the peer interactions of an autistic student within the classroom. METHOD: Drawing on the bioecological model of human development, this situated discourse analysis used thematic coding and microanalysis to examine data from semistructured interviews and 10 sessions of direct classroom observations of a 9-year-old autistic student and his classroom communication partners. RESULTS: Convergent data across participants, time, and data sources revealed the following systemic influences on peer interaction: predominant medicalized view of autism (macrosystem), educational practices (exosystem), misaligned roles across adults and peers in the classroom (mesosystem), and multimodal opportunities for direct interaction that were supported by objects and physical contact and inhibited by rapid pacing (microsystem). CONCLUSIONS: Findings illustrate the environmental complexities associated with the development of peer interactions for autistic students. We offer explicit clinical implications for how environmental factors can be addressed in the school-based eligibility determination process and in the Individualized Education Program.


Subject(s)
Autistic Disorder , Adult , Humans , Child , Peer Group , Schools , Students , Communication
5.
Biosensors (Basel) ; 12(9)2022 Aug 24.
Article in English | MEDLINE | ID: mdl-36140059

ABSTRACT

Two key features of cancer cells are sustained proliferation and invasion, which is preceded by a modification of the adhesion properties to the extracellular matrix. Currently, fluorescence-based techniques are mainly used to detect these processes, including flow cytometry and fluorescence resonance energy transfer (FRET) microscopy. We have previously described a simple, fast and label-free method based on a gold nanohole array biosensor to detect the spectral response of single cells, which is highly dependent on the actin cortex. Here we used this biosensor to study two cellular processes where configuration of the actin cortex plays an essential role: cell cycle and cell-matrix adhesion. Colorectal cancer cells were maintained in culture under different conditions to obtain cells stopped either in G0/G1 (resting cells/cells at the initial steps of cell growth) or G2 (cells undergoing division) phases of the cell cycle. Data from the nanohole array biosensor showed an ability to discriminate between both cell populations. Additionally, cancer cells were monitored with the biosensor during the first 60 min after cells were deposited onto a biosensor coated with fibronectin, an extracellular matrix protein. Spectral changes were detected in the first 20 min and increased over time as the cell-biosensor contact surface increased. Our data show that the nanohole array biosensor provides a label-free and real-time procedure to detect cells undergoing division or changes in cell-matrix interaction in both clinical and research settings.


Subject(s)
Biosensing Techniques , Neoplasms , Actins , Biosensing Techniques/methods , Cell Division , Fibronectins , Gold
6.
Biomedicines ; 10(5)2022 May 10.
Article in English | MEDLINE | ID: mdl-35625843

ABSTRACT

Glioblastoma (GBM) is one of the most aggressive cancers, with dismal prognosis despite continuous efforts to improve treatment. Poor prognosis is mostly due to the invasive nature of GBM. Thus, most research has focused on studying the molecular players involved in GBM cell migration and invasion of the surrounding parenchyma, trying to identify effective therapeutic targets against this lethal cancer. Our laboratory discovered the implication of TENM1, also known as ODZ1, in GBM cell migration in vitro and in tumor invasion using different in vivo models. Moreover, we investigated the microenvironmental stimuli that promote the expression of TENM1 in GBM cells and found that macrophage-secreted IL-6 and the extracellular matrix component fibronectin upregulated TENM1 through activation of Stat3. We also described that hypoxia, a common feature of GBM tumors, was able to induce TENM1 by both an epigenetic mechanism and a HIF2α-mediated transcriptional pathway. The fact that TENM1 is a convergence point for various cancer-related signaling pathways might give us a new therapeutic opportunity for GBM treatment. Here, we briefly review the findings described so far about the mechanisms that control the expression of the GBM invasion factor TENM1.

7.
Int J Mol Sci ; 23(2)2022 Jan 11.
Article in English | MEDLINE | ID: mdl-35054927

ABSTRACT

Background: Glioblastoma (GBM) remains a major clinical challenge due to its invasive capacity, resistance to treatment, and recurrence. We have previously shown that ODZ1 contributes to glioblastoma invasion and that ODZ1 mRNA levels can be upregulated by epigenetic mechanisms in response to hypoxia. Herein, we have further studied the transcriptional regulation of ODZ1 in GBM stem cells (GSCs) under hypoxic conditions and analyzed whether HIF2α has any role in this regulation. Methods: We performed the experiments in three primary GSC cell lines established from tumor specimens. GSCs were cultured under hypoxia, treated with HIF regulators (DMOG, chetomin), or transfected with specific siRNAs, and the expression levels of ODZ1 and HIF2α were analyzed. In addition, the response of the ODZ1 promoter cloned into a luciferase reporter plasmid to the activation of HIF was also studied. Results: The upregulation of both mRNA and protein levels of HIF2α under hypoxia conditions correlated with the expression of ODZ1 mRNA. Moreover, the knockdown of HIF2α by siRNAs downregulated the expression of ODZ1. We found, in the ODZ1 promoter, a HIF consensus binding site (GCGTG) 1358 bp from the transcription start site (TSS) and a HIF-like site (CCGTG) 826 bp from the TSS. Luciferase assays revealed that the stabilization of HIF by DMOG resulted in the increased activity of the ODZ1 promoter. Conclusions: Our data indicate that the HIF2α-mediated upregulation of ODZ1 helps strengthen the transcriptional control of this migration factor under hypoxia in glioblastoma stem cells. The discovery of this novel transcriptional pathway identifies new targets to develop strategies that may avoid GBM tumor invasion and recurrence.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Gene Expression Regulation, Neoplastic , Glioblastoma/etiology , Glioblastoma/metabolism , Neoplastic Stem Cells/metabolism , Nerve Tissue Proteins/genetics , Tenascin/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , Cell Hypoxia , Cell Line, Tumor , Gene Knockdown Techniques , Glioblastoma/pathology , Humans , Neoplastic Stem Cells/pathology , Nerve Tissue Proteins/metabolism , RNA, Messenger/genetics , Tenascin/metabolism
9.
Nutr Neurosci ; 25(7): 1400-1412, 2022 Jul.
Article in English | MEDLINE | ID: mdl-33345728

ABSTRACT

OBJECTIVES: The brains of individuals with Down syndrome (DS) present defects in neurogenesis and synaptogenesis during prenatal and early postnatal stages that are partially responsible for their cognitive disabilities. Because oleic and linolenic fatty acids enhance neurogenesis, synaptogenesis, and cognitive abilities in rodents and humans, in this study we evaluated the ability of these compounds to restore these altered phenotypes in the Ts65Dn (TS) mouse model of DS during early postnatal stages. METHODS: TS and euploid mice were treated with oleic or linolenic acid from PD3 to PD15, and the short- and long- term effects of these acids on neurogenesis and synaptogenesis were evaluated. The effects of these treatments on the cognitive abilities of TS mice during early adulthood were also evaluated. RESULTS: Administration of oleic or linolenic acid did not modify cell proliferation immediately after treatment discontinuation or several weeks later. However, oleic acid increased the total number of DAPI+ cells (+ 26%), the percentage of BrdU+ cells that acquired a neural phenotype (+ 9.1%), the number of pre- (+ 29%) and post-synaptic (+ 32%) terminals and the cognitive abilities of TS mice (+ 18.1%). In contrast, linolenic acid only produced a slight cognitive improvement in TS mice. (+12.1%). DISCUSSION: These results suggest that early postnatal administration of oleic acid could palliate the cognitive deficits of DS individuals.


Subject(s)
Down Syndrome , Animals , Cognition , Disease Models, Animal , Down Syndrome/genetics , Down Syndrome/therapy , Female , Hippocampus , Mice , Mice, Inbred C57BL , Mice, Transgenic , Oleic Acid , Pregnancy , alpha-Linolenic Acid/therapeutic use
10.
Sci Rep ; 11(1): 16196, 2021 08 10.
Article in English | MEDLINE | ID: mdl-34376733

ABSTRACT

We have previously shown that the transmembrane protein ODZ1 serves for glioblastoma (GBM) cells to invade the surrounding tissue through activation of RhoA/ROCK pathway. However, the transcriptional machinery used by GBM cells to regulate the expression of ODZ1 is unknown. Here we show that interaction with tumor microenvironment elements, mainly activated monocytes through IL-6 secretion, and the extracellular matrix protein fibronectin, induces the Stat3 transcriptional pathway and upregulates ODZ1 which results in GBM cell migration. This signaling route is abrogated by blocking the IL-6 receptor, inhibiting Jak kinases or knocking down Stat3. Furthermore, we have identified a Stat3 responsive element in the ODZ1 gene promoter, about 1 kb from the transcription start site. Luciferase-reporter assays confirmed that the promoter responds to the presence of monocytic cells and this activation is greatly reduced when the Stat3 site is mutated or following treatment with a neutralizing anti-IL-6 receptor antibody or transfecting GBM cells with a dominant negative variant of Stat3. Overall, we show that monocyte-secreted IL-6 and the extracellular matrix protein fibronectin activate the axis Stat3-ODZ1 and promote migration of GBM cells. This is the first described transcriptional mechanism used by tumor cells to promote the expression of the invasion factor ODZ1.


Subject(s)
Gene Expression Regulation, Neoplastic , Glioblastoma/pathology , Interleukin-6/metabolism , Nerve Tissue Proteins/metabolism , STAT3 Transcription Factor/metabolism , Tenascin/metabolism , Transcriptional Activation , Tumor Microenvironment , Cell Movement , Glioblastoma/genetics , Glioblastoma/immunology , Glioblastoma/metabolism , Humans , Nerve Tissue Proteins/genetics , Promoter Regions, Genetic , Receptors, Interleukin-6/metabolism , STAT3 Transcription Factor/genetics , Signal Transduction , Tenascin/genetics , Tumor Cells, Cultured
11.
Sci Rep ; 11(1): 16597, 2021 08 16.
Article in English | MEDLINE | ID: mdl-34400680

ABSTRACT

Pulmonary vascular resistance (PVR) is a marker of pulmonary vascular remodeling. A non-invasive model assessed by cardiovascular magnetic resonance (CMR) has been proposed to estimate PVR. However, its accuracy has not yet been evaluated in patients with heart failure. We prospectively included 108 patients admitted with acute heart failure (AHF), in whom a right heart catheterization (RHC) and CMR were performed at the same day. PVR was estimated by CMR applying the model: PVR = 19.38 - [4.62 × Ln pulmonary artery average velocity (in cm/s)] - [0.08 × right ventricle ejection fraction (in %)], and by RHC using standard formulae. The median age of the cohort was 67 years (interquartile range 58-73), and 34% were females. The median of PVR assessed by RHC and CMR were 2.2 WU (1.5-4) and 5 WU (3.4-7), respectively. We found a weak correlation between invasive PVR and PVR assessed by CMR (Spearman r = 0.21, p = 0.02). The area under the ROC curve for PVR assessed by CMR to detect PVR ≥ 3 WU was 0.57, 95% confidence interval (CI): 0.47-0.68. In patients with AHF, the non-invasive estimation of PVR using CMR shows poor accuracy, as well as a limited capacity to discriminate increased PVR values.


Subject(s)
Heart Failure/physiopathology , Models, Cardiovascular , Vascular Resistance , Aged , Area Under Curve , Cardiac Catheterization , Female , Heart Failure/blood , Heart Failure/diagnostic imaging , Humans , Magnetic Resonance Imaging, Cine , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prospective Studies , ROC Curve , Stroke Volume , Vascular Remodeling
12.
Sleep Med ; 85: 191-195, 2021 09.
Article in English | MEDLINE | ID: mdl-34343769

ABSTRACT

OBJECTIVE: To evaluate the relation between systemic iron parameters (SIP) and substantia nigra (SN) iron deposits, as assessed by transcranial sonography (TCS) in restless legs syndrome (RLS). METHODS: We conducted a cross-sectional study in RLS patients, from whom blood samples with SIP were obtained, consisting of total iron-binding capacity (TIBC), serum ferritin, hemoglobin, transferrin saturation (TSAT), serum iron, and serum transferrin. TCS was performed over the SN, and the substantia nigra echogenicity index (SNEI) was determined according to established methods. Symptom severity was evaluated using the international restless legs scale (IRLS). A Spearman correlation was performed. RESULTS: A total of 167 patients were studied. Correlations between SNEI and SIP were as follows: serum ferritin (R = 0.0422; n.s.), TSAT (R = 0.0883; n.s.), TIBC (R = -0.1091; n.s.), serum transferrin (R = -0.0420; n.s.), hemoglobin (R = 0.0185; n.s.), serum iron (R = 0.0389; n.s.). No correlation was found with age and IRLS (R = 0.1375; n.s. and R = 0.0880, n.s., respectively). CONCLUSIONS: SIP are not correlated with SN iron content in RLS, quantified by means of TCS. TCS of the SN might be a more valid estimate and could be useful in the evaluation of RLS patients.


Subject(s)
Restless Legs Syndrome , Cross-Sectional Studies , Humans , Iron , Restless Legs Syndrome/diagnostic imaging , Substantia Nigra/diagnostic imaging , Ultrasonography, Doppler, Transcranial
13.
Front Pharmacol ; 12: 613211, 2021.
Article in English | MEDLINE | ID: mdl-33935706

ABSTRACT

All individuals with Down syndrome (DS) eventually develop Alzheimer's disease (AD) neuropathology, including neurodegeneration, increases in ß-amyloid (Aß) expression, and aggregation and neurofibrillary tangles, between the third and fourth decade of their lives. There is currently no effective treatment to prevent AD neuropathology and the associated cognitive degeneration in DS patients. Due to evidence that the accumulation of Aß aggregates in the brain produces the neurodegenerative cascade characteristic of AD, many strategies which promote the clearance of Aß peptides have been assessed as potential therapeutics for this disease. Bexarotene, a member of a subclass of retinoids that selectively activates retinoid receptors, modulates several pathways essential for cognitive performance and Aß clearance. Consequently, bexarotene might be a good candidate to treat AD-associated neuropathology. However, the effects of bexarotene treatment in AD remain controversial. In the present study, we aimed to elucidate whether chronic bexarotene treatment administered to the most commonly used murine model of DS, the Ts65Dn (TS) mouse could reduce Aß expression in their brains and improve their cognitive abilities. Chronic administration of bexarotene to aged TS mice and their CO littermates for 9 weeks diminished the reference, working, and spatial learning and memory of TS mice, and the spatial memory of CO mice in the Morris water maze. This treatment also produced marked hypoactivity in the plus maze, open field, and hole board tests in TS mice, and in the open field and hole board tests in CO mice. Administration of bexarotene reduced the expression of Aß1-40, but not of Aß1-42, in the hippocampi of TS mice. Finally, bexarotene increased Thyroid-stimulating hormone levels in TS mice and reduced Thyroid-stimulating hormone levels in CO mice, while animals of both karyotypes displayed reduced thyroxine levels after bexarotene administration. The bexarotene-induced hypothyroidism could be responsible for the hypoactivity of TS and CO mice and their diminished performance in the Morris water maze. Together, these results do not provide support for the use of bexarotene as a potential treatment of AD neuropathology in the DS population.

14.
ESC Heart Fail ; 7(6): 3792-3800, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32964683

ABSTRACT

AIMS: The aim of this study was to evaluate the safety profile in terms of changes in renal function after co-treatment with sacubitril/valsartan and empagliflozin in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: This multicentre observational analysis included 108 patients with T2D and HFrEF treated with both agents: baseline sacubitril/valsartan (Group A; n = 43), baseline empagliflozin (Group B; n = 42), or both agents initiated simultaneously (Group C; n = 23). The primary endpoint was estimated glomerular filtration rate (eGFR) dynamics across treatment groups. A binary characterization of worsening renal function (WRF)/improved renal function (IRF) was included in the primary endpoint. WRF and IRF were defined as an increase/decrease in serum creatinine ≥ 0.3 mg/dL or GFR ≥ 20%. Changes in quantitative variables were evaluated using joint modelling of survival and longitudinal data (JM). Rates and their treatment differences were determined by Poisson regression. The mean left ventricle ejection fraction and eGFR were 32 ± 6% and 70 ± 28 mL/min/1.73 m2 , respectively. At a median follow-up of 1.01 years (inter-quartile range 0.71-1.50), 377 outpatient visits were recorded. Although there were differences in GFR trajectories over time within each treatment, they did not achieve statistical significance (omnibus P = 0.154). However, when these differences were contrasted among groups, there was a significant decrease in GFR in Group A as compared with Group B (P = 0.002). The contrast between Groups C and B was not significant (P = 0.430). These differences were also reflected when the rates for WRF and IRF were contrasted among treatments. CONCLUSIONS: The co-administration of sacubitril/valsartan and empagliflozin in patients with HFrEF and concomitant T2D appears to be safe in terms of renal function.

15.
Sleep Med ; 74: 48-55, 2020 10.
Article in English | MEDLINE | ID: mdl-32841843

ABSTRACT

OBJECTIVE: To evaluate the incidence of iron overload and anaphylaxis following intravenous (IV) iron treatment of restless legs syndrome (RLS). METHODS: A total of 58 consecutive RLS patients, meeting clinical requirements for IV iron treatment according to current IRLSSG guidelines were recruited. IV iron treatment consisted of two 500 mg infusions of ferric carboxymaltose (FCM) administered five days apart. During each of the three follow-up visits we obtained blood samples, substantia nigra echogenity index (SNEI) by means of transcranial sonography (TCS), and assessed the severity of RLS symptoms (IRLS scale). "Iron overload risk" was defined as transferrin saturation (TSAT) > 45% on two consecutive follow-up visits. In patients who had a reduction in systemic iron levels following treatment, an additional 500 mg of FCM was administered when feasible. In such cases an additional two follow-up visits were performed. RESULTS: Among the total sample, only 2/58 participants met criteria for iron overload risk. They had no evidence of liver damage and did not require additional treatment. Among the 21 patients receiving an additional 500 mg infusion after, only one patient was diagnosed with iron overload risk. Among these three patients, only one was a hemochromatosis gene carrier. No anaphylaxis or other side-effects were reported. CONCLUSIONS: In real-life clinical conditions, the risk of iron overload is low when IV FCM is administered according to the safety limits defined in the current RLS treatment guidelines. However, a close clinical follow-up with periodic blood sampling for iron status, is needed.


Subject(s)
Anaphylaxis , Iron Overload , Restless Legs Syndrome , Anaphylaxis/chemically induced , Anaphylaxis/drug therapy , Humans , Iron , Iron Overload/drug therapy , Restless Legs Syndrome/drug therapy , Treatment Outcome
16.
J Nutr ; 150(9): 2478-2489, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32729926

ABSTRACT

BACKGROUND: The cognitive dysfunction in Down syndrome (DS) is partially caused by deficient neurogenesis during fetal stages. Curcumin enhances neurogenesis and learning and memory. OBJECTIVES: We aimed to test the ability of curcumin to rescue the neuromorphological and cognitive alterations of the Ts65Dn (TS) mouse model of DS when administered prenatally or during early postnatal stages, and to evaluate whether these effects were maintained several weeks after the treatment. METHODS: To evaluate the effects of prenatal curcumin administration, 65 pregnant TS females were subcutaneously treated with curcumin (300 mg/kg) or vehicle from ED (Embryonic Day) 10 to PD (Postnatal Day) 2. All the analyses were performed on their TS and Control (CO) male and female progeny. At PD2, the changes in neurogenesis, cellularity, and brain weight were analyzed in 30 TS and CO pups. The long-term effects of prenatal curcumin were evaluated in another cohort of 44 TS and CO mice between PD30 and PD45. The neuromorphological effects of the early postnatal administration of curcumin were assessed on PD15 in 30 male and female TS and CO pups treated with curcumin (300 mg/kg) or vehicle from PD2 to PD15. The long-term neuromorphological and cognitive effects were assessed from PD60 to PD90 in 45 mice. Data was compared by ANOVAs. RESULTS: Prenatal administration of curcumin increased the brain weight (+45%, P < 0.001), the density of BrdU (bromodeoxyuridine)- (+150%, P < 0.001) and DAPI (4',6-diamidino-2-phenylindole)- (+38%, P = 0.005) positive cells, and produced a long-term improvement of cognition in TS (+35%, P = 0.007) mice with respect to vehicle-treated mice. Postnatal administration of curcumin did not rescue any of the short- or long-term altered phenotypes of TS mice. CONCLUSION: The beneficial effects of prenatal curcumin administration to TS mice suggest that it could be a therapeutic strategy to treat DS cognitive disabilities.


Subject(s)
Brain/growth & development , Cognition/drug effects , Curcumin/pharmacology , Down Syndrome/drug therapy , Neurogenesis/drug effects , Animal Feed/analysis , Animals , Brain/drug effects , Curcumin/administration & dosage , Diet/veterinary , Drug Administration Schedule , Female , Injections, Subcutaneous , Male , Mice , Mice, Transgenic , Pregnancy , Prenatal Exposure Delayed Effects
17.
Lang Speech Hear Serv Sch ; 51(3): 671-686, 2020 07 15.
Article in English | MEDLINE | ID: mdl-32392446

ABSTRACT

Purpose The present clinical focus draws on an intrinsic case study to provide a thick description of the communication profile of John, a 9-year-old minimally verbal autistic student. Method Specifically, traditional behavioral assessments, classroom video observations, and semistructured interviews were used to gather information regarding John's communication profile and potential sensory-motor differences. Results Convergent evidence indicated that John's expressive profile was characterized by single words, emergent word combinations, some conventional gestures, and a low frequency of communicative initiations. Concomitant language comprehension challenges and poor intelligibility associated with motor speech impairment were also indicated. His sensory-motor profile was marked by fine motor impairment, relative strengths in gross motor abilities, and sensory differences across visual, hearing, and tactile modalities. Conclusion Direct implications for supporting minimally verbal autistic students like John include the need to (a) consider sensory-motor influences on social interaction and (b) support flexible use of multimodal communication resources, including augmentative and alternative communication. Supplemental Material https://doi.org/10.23641/asha.12202448.


Subject(s)
Autistic Disorder/psychology , Communication , Child , Humans , Male
18.
J Nutr ; 150(6): 1631-1643, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32243527

ABSTRACT

BACKGROUND: The cognitive impairments that characterize Down syndrome (DS) have been attributed to brain hypocellularity due to neurogenesis impairment during fetal stages. Thus, enhancing prenatal neurogenesis in DS could prevent or reduce some of the neuromorphological and cognitive defects found in postnatal stages. OBJECTIVES: As fatty acids play a fundamental role in morphogenesis and brain development during fetal stages, in this study, we aimed to enhance neurogenesis and the cognitive abilities of the Ts65Dn (TS) mouse model of DS by administering oleic or linolenic acid. METHODS: In total, 85 pregnant TS females were subcutaneously treated from Embryonic Day (ED) 10 until Postnatal Day (PD) 2 with oleic acid (400 mg/kg), linolenic acid (500 mg/kg), or vehicle. All analyses were performed on their TS and Control (CO) male and female progeny. At PD2, we evaluated the short-term effects of the treatments on neurogenesis, cellularity, and brain weight, in 40 TS and CO pups. A total of 69 TS and CO mice were used to test the long-term effects of the prenatal treatments on cognition from PD30 to PD45, and on neurogenesis, cellularity, and synaptic markers, at PD45. Data were compared by ANOVAs. RESULTS: Prenatal administration of oleic or linolenic acid increased the brain weight (+36.7% and +45%, P < 0.01), the density of BrdU (bromodeoxyuridine)- (+80% and +115%; P < 0.01), and DAPI (4',6-diamidino-2-phenylindole)-positive cells (+64% and +22%, P < 0.05) of PD2 TS mice with respect to the vehicle-treated TS mice. Between PD30 and PD45, TS mice prenatally treated with oleic or linolenic acid showed better cognitive abilities (+28% and +25%, P < 0.01) and a higher density of the postsynaptic marker PSD95 (postsynaptic density protein 95) (+65% and +44%, P < 0.05) than the vehicle-treated TS animals. CONCLUSION: The beneficial cognitive and neuromorphological effects induced by oleic or linolenic acid in TS mice suggest that they could be promising pharmacotherapies for DS-associated cognitive deficits.


Subject(s)
Down Syndrome/physiopathology , Maternal Exposure , Oleic Acid/administration & dosage , alpha-Linolenic Acid/administration & dosage , Animals , Body Weight/drug effects , Brain/drug effects , Cognition/drug effects , Disease Models, Animal , Down Syndrome/pathology , Female , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Transgenic , Neurogenesis/drug effects , Oleic Acid/pharmacology , Organ Size/drug effects , Pregnancy , Prenatal Exposure Delayed Effects , alpha-Linolenic Acid/pharmacology
19.
PLoS One ; 13(10): e0206344, 2018.
Article in English | MEDLINE | ID: mdl-30365558

ABSTRACT

OBJECTIVE: We characterized the dynamics of eosinophils in blood and in the infarcted myocardium in patients and in a swine model of reperfused myocardial infarction (MI). The association of eosinophil dynamics with various outcomes was assessed. METHODS: Serial eosinophil count and pre-discharge cardiac magnetic resonance were carried out in a prospective series of 620 patients with a first ST-elevation MI. In a swine model of reperfused MI, the dynamics of circulating eosinophils and their presence in the infarcted myocardium were determined. In autopsies from chronic MI patients, eosinophils were quantified. RESULTS: Patient eosinophil count sharply decreased 12h post-reperfusion compared to arrival. A lower minimum eosinophil count was associated with more extensive edema, microvascular obstruction, and infarct size as measured by cardiac magnetic resonance, and also with a higher rate of cardiac events (death, re-infarction, or heart failure) during follow-up. In the experimental model, eosinophil count boosted during ischemia and dropped back immediately post-reperfusion. Myocardial samples revealed progressive eosinophil migration into the infarcted myocardium, especially areas with microvascular obstruction. Markers of eosinophil maturation and survival (interleukin-5), degranulation (eosinophil cationic protein) and migration (eotoxin-1) were detected in the blood of patients, and in porcine myocardium. Eosinophil infiltration was detected in autopsies from chronic MI patients. CONCLUSION: Eosinopenia post-MI was associated with an impaired cardiac structure and adverse events. The decay in circulating eosinophils soon after reperfusion mirrors their migration into the infarcted myocardium, as reflected by their presence in heart samples from swine and patients. Further studies are needed to understanding this unexplored pathway and its therapeutic implications.


Subject(s)
Eosinophils/cytology , Myocardial Infarction/blood , Myocardial Infarction/surgery , Myocardial Reperfusion , Animals , Cell Count , Cytokines/metabolism , Female , Humans , Male , Middle Aged , Myocardial Infarction/metabolism , Swine
20.
Rev Port Cardiol (Engl Ed) ; 37(8): 717.e1-717.e5, 2018 Aug.
Article in English, Portuguese | MEDLINE | ID: mdl-29934214

ABSTRACT

Prosthetic valve endocarditis is a major diagnostic challenge in clinical practice, due to the lower sensitivity of the modified Duke criteria and a higher percentage of cases with negative or inconclusive echocardiography results. The delay in establishing medical and surgical treatment increases the morbidity/mortality rate. New imaging techniques and 18F-FDG PET/CT in particular have meant a significant advance in cases of high clinical suspicion and negative or inconclusive echocardiography, increasing the overall sensitivity of the modified Duke criteria. We report the case of a male patient with prosthetic valve endocarditis, where 18F-FDG PET/CT provided the diagnostic key, determining the origin of the endocarditis and avoiding treatment delay.


Subject(s)
Endocarditis, Bacterial/diagnostic imaging , Fluorodeoxyglucose F18 , Heart Valve Prosthesis , Positron Emission Tomography Computed Tomography , Prosthesis-Related Infections/diagnostic imaging , Radiopharmaceuticals , Staphylococcal Infections/diagnostic imaging , Staphylococcus aureus , Endocarditis, Bacterial/etiology , Heart Valve Prosthesis/adverse effects , Humans , Male , Middle Aged , Prosthesis-Related Infections/etiology , Staphylococcal Infections/etiology
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