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OBJECTIVE: The aim of this study was to evaluate the nonfatal drowning experience, risk factors, intrahospital assessment and postincidental outcomes for children admitted to King Fahd Hospital of the University, AlKhobar, Saudi Arabia, over a 10-year period. METHODS: Children up to the age of 14 years who were admitted with the diagnosis of nonfatal drowning from July 2005 to June 2015 were included. Data regarding demographics, timing, season and location of drowning, presence of an assigned lifeguard, duration of submersion and transport to hospital, cardiopulmonary resuscitation, initial Glasgow Coma Scale, temperature, pH, blood sugar level, total hospital stay, and discharge status were extrapolated, and their effects on the patient's outcome analyzed. Patients' outcomes were classified into either full recovery, moderate to severe neurological damage, or brain death. RESULTS: Fifty-one subjects were included in the study; 66.7% were males, 57% were younger than 6 years, and 80% were Saudi citizens. Of the total cases, 94% recovered fully, and 6% were diagnosed as having brain death or discharged from the intensive care unit with severe neurological injury. Submersion time of more than 5 minutes, Glasgow Coma Scale of 4 or less, pH of less than 7.1, temperature of 35°C or less, and blood sugar of 180 mg/dL or greater were found to correlate with bad outcomes with great statistical significance. CONCLUSIONS: The findings of this study were in line with results of most of the international and local studies on the subject. Significant defects have been concluded in prehospital medical care and cardiopulmonary resuscitation. Adequate swimming safety regulations, assignments of lifeguards, and parental education should be taken into consideration by media and involved authorities.
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Afogamento Iminente/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Hospitais Universitários/estatística & dados numéricos , Humanos , Lactente , Masculino , Afogamento Iminente/etiologia , Estudos Retrospectivos , Fatores de Risco , Arábia Saudita/epidemiologiaRESUMO
This work aimed to characterize dust-fall samples collected from street's trees in Greater Cairo (GC), Egypt, and its surroundings by different spectroscopic techniques, namely; X-ray diffraction (XRD), attenuated total-reflection Fourier transform infrared (ATR-FTIR), particle-size analyzer, and scanning electron microscopy (SEM) combined with energy dispersive X-ray measurements. Samples were collected from 19 different locations inside and outside of GC. Quantitative phase analysis of the dust-fall samples was performed using the Rietveld method. Results showed that the most frequently observed phases in the dust-fall samples were calcite (CaCO3), dolomite (CaMg(CO3)2), gypsum (CaSO4·2H2O), and quartz (SiO2) with average concentrations of 39 ± 16, 8 ± 7, 22 ± 13, and 33 ± 14 wt%, respectively. The occurrence of these constituents referred to a combination of different anthropogenic and natural sources. The ATR-FTIR results are in good agreements with XRD data of the different observed phases. Based on the SEM and particle-size measurements, quantitative determination of the particle-size distribution was described. It was found that not only the large-sized particles are deposited but also the small-sized ones (PM10 and PM2.5). In addition, the particle size of the collected dust-fall samples varied from 0.1 to 200 µm with an average particle size of 17.36 µm; however, the particle size ranged from 2.5 to 40 µm predominated in all of the dust-fall samples.
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Poluentes Atmosféricos/análise , Poeira/análise , Monitoramento Ambiental , Carbonato de Cálcio , Egito , Magnésio , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Quartzo , Dióxido de SilícioRESUMO
Background: Limbic encephalitis (LE) is a rare variant of autoimmune encephalitis. It often manifests with subacute neuropsychiatric symptoms of agitation, delusions, variable seizure semiology, and short-term memory loss. Seronegative limbic encephalitis can pose a diagnostic conundrum owing to its inadequately understood pathophysiology. Case presentation: We report a rare case of a young male with subacute neuropsychiatric manifestations of delusions, agitations and seizures. He was diagnosed with seronegative limbic encephalitis (SNLE). Brain MRI demonstrated bilateral Claustrum sparing sign. An EEG showed continuous left-sided epileptiform discharges in periodic to predominantly left middle temporal. Patient condition gradually improved with pulsed methylprednisolone, intravenous immunoglobulins and anti-seizure medications. Conclusion: Claustrum remains one of the least understood neuroanatomical structures. Claustrum sign has been reported in febrile infection-related epilepsy syndrome (FIRES), LE, and autoimmune refractory epilepsy. To the best of our knowledge, we report the first case in literature with Claustrum sparing sign in seronegative Limbic Encephalitis. Further experimental models and researches are warranted to better understand the unique function of the claustrum and unravel possible other attributable auto-antibodies, which could alter treatment and prognosis.
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OBJECTIVE: To audit physicians' adherence to the local antibiotic policy guidelines in government hospitals in Kuwait. MATERIALS AND METHODS: The study was a retrospective review of patient records in nine hospitals between July 1 and December 31, 2008. Clinical notes and medication charts of the latest hospital admissions were checked for antibiotic prescribing. On the audit form, aspects of the prescribed antibiotic were benchmarked to the hospital antibiotic policy guidelines to evaluate adherence. RESULTS: Of 2,232 reviewed records, 1,112 (49.8%) patients had 1,528 antibiotic prescriptions. Patients who received antibiotics were significantly younger than those who did not (median age: 26.3 vs. 29.8 years, p < 0.001) and their hospital stay was significantly longer (median: 4 vs. 2 days, p < 0.001). The choice of an antibiotic was appropriate and matched the policy in 806 (52.7%) prescriptions. Of such appropriate antibiotics, adherence to route of administration was observed in 768/806 (95.3%), to dose in 758 (94%), to frequency in 746 (92.6%) and to duration in 608 (75.4%). Full adherence to all aspects of antibiotic choice, dose, route, frequency and duration was achieved in 464 (30.4%) prescriptions. In 382 (25%), the antibiotics administered were not indicated. CONCLUSION: There was low adherence to the local antibiotic policy guidelines. Physicians' antibiotic prescribing practices should be optimized. Adherence to, and update of, the policy is recommended.
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Antibacterianos/administração & dosagem , Fidelidade a Diretrizes/estatística & dados numéricos , Médicos/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Adulto , Uso de Medicamentos , Feminino , Humanos , Revisão da Utilização de Seguros/estatística & dados numéricos , Kuweit , Masculino , Auditoria Médica , Prontuários Médicos/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Estudos RetrospectivosRESUMO
In the original publication [...].
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CASE PRESENTATION: A 58-year-old man presented to the ED with a 1-week history of progressive weight loss, generalized weakness, unsteadiness, and dizziness. In hospital, he experienced a witnessed episode of loss of consciousness with no observable respirations that lasted for 15 minutes. His arterial blood gas demonstrated hypercapnic respiratory failure, and he required mask ventilation and vasoactive medications. Similar episodes occurred several more times over the course of the night that required the patient to be intubated. The paroxysmal episodes persisted necessitating continued invasive ventilatory support and admission to the ICU. The episodes occurred in both awake and asleep states and required the ventilator settings to dictate a minimum rate, but minimal ventilatory support otherwise. Further history revealed other symptomatic complaints of vertigo, dysphagia, and hypophonia that had progressed over a 2-month period. The patient's medical history was pertinent for a diagnosis of prostatic carcinoma 3 years previously that was found to be castrate resistant. He had metastases to his hip, ribs, and thoracic spine. Previous treatments had included bicalutamide, docetaxel, and abiraterone; he was receiving leuprolide therapy on presentation.
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Síndromes Paraneoplásicas do Sistema Nervoso/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In ferromagnetic semiconductors, the coupling of magnetic ordering with semiconductor character accelerates the quantum computing. The structural stability, Curie temperature (Tc), spin polarization, half magnetic ferromagnetism and transport properties of ZnX2Se4 (X = Ti, V, Cr) chalcogenides for spintronic and thermoelectric applications are studied here by density functional theory (DFT). The highest value of Tc is perceived for ZnCr2Se4. The band structures in both spin channels confirmed half metallic ferromagnetic behavior, which is approved by integer magnetic moments (2, 3, 4) µB of Ti, V and Cr based spinels. The HM behavior is further measured by computing crystal field energy ΔEcrystal, exchange energies Δx(d), Δx (pd) and exchange constants (Noα and Noß). The thermoelectric properties are addressed in terms of electrical conductivity, thermal conductivity, Seebeck coefficient and power factor in within a temperature range 0-400 K. The positive Seebeck coefficient shows p-type character and the PF is highest for ZnTi2Se4 (1.2 × 1011 W/mK2) among studied compounds.
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BACKGROUND: The aim of this study is to validate the Arabic version of the Basic Psychological Need Satisfaction and Frustration Scale (BPNSFS), and to investigate the extent of its invariance across five Arab countries and gender. METHODS: A back-translated version of the BPNSFS, the second version of the Beck Depression Inventory (BDI-II), and the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) were administered to a sample consisting of 1082 undergraduate students affiliated with universities in five Arab countries (487 males and 595 females: Mage = 20.04 ± 1.87 years). The data of the BPNSFS were examined for univariate and multivariate normality using Shapiro-Wilk tests and Mardia's coefficient, respectively. To evaluate and compare the four models with confirmatory factor analysis (CFA), we used the following goodness-of-fit indices: the chi-square value (χ2), comparative fit index (CFI), Tucker-Lewis index (TLI), Root Mean-Square Error of Approximation (RMSEA), and Baysian Information Criterion (BIC). A multi-group CFA [Byrne in Structural equation modeling with EQS: basic concepts, applications, and programming, Routledge, Abingdon, 2013] on the BPNSFS structure to examine its invariance across the five Arab countries and across genders. RESULTS: The results of confirmatory factor analysis supported the generalizability of the BPNSFS's six-factor model to the five Arab countries. The relationships between the six psychological needs satisfaction and frustrations and both mental health and symptoms of depression provide additional evidence on the construct validity of the BPNSFS through cross cultural data. The findings of BPNSFS's measurement invariance across males and females and across the five Arab countries help ensure that the latent means are comparable across these different groups. CONCLUSIONS: The study concluded that the Arabic version of the BPNSFS which measures satisfaction and frustration of the three basic needs (autonomy, competency, and relatedness) is proved to be invariant across the five Arab countries and gender and can be used to compare the basic psychological needs in the Arab context.
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Frustração , Satisfação Pessoal , Psicometria , Análise Fatorial , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
This is a retrospective single-center study of 417 consecutive patients with coronavirus disease 2019 (COVID-19) admitted to Jaber Al-Ahmad Hospital in Kuwait between February 24, 2020 and May 24, 2020. In total, 39.3% of patients were asymptomatic, 41% were symptomatic with mild/moderate symptoms, 19.7% were admitted to the intensive care unit (ICU). Most common symptoms in cohort patients were fever (34.3%) and dry cough (32.6%) while shortness in breath was reported in (75.6%) of ICU admissions. Reported complications requiring ICU admission included Sepsis (68.3%), acute respiratory distress syndrome (95.1%) and heart failure (63.4%). ICU patients were more likely to have comorbidities, in comparison to non-ICU patients, including diabetes (35.4% vs 20.3%) and hypertension (40.2% vs 26.9%). Mortality rate of cohort was 14.4% and mean age of death was 54.20 years (± 11.09) and 90% of death cases were males. Chest high-resolution computed tomography for ICU cases reveled multifocal large patchy areas of ground glass opacification mixed with dense consolidation. Cases admitted to ICU showed abnormal levels of markers associated with infection, inflammation, abnormal blood clotting, heart problems and kidney problems. Mean hospital stay for asymptomatic cases was 20.69 days ±8.57 and for mild/moderate cases was 21.4 days ±8.28. Mean stay in ICU to outcome for survivors was 11.95 days ±8.96 and for death cases 13.15 days ±10.02. In this single-center case series of 417 hospitalized COVID-19 patients in Kuwait 39.3% were asymptomatic cases, 41% showed mild/moderate symptoms and 18.7% were admitted to ICU with a mortality rate of 14.4%.
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Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Assintomáticas/epidemiologia , Betacoronavirus , COVID-19 , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva , Kuweit/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Adulto JovemRESUMO
AIMS: Ambulatory video-EEG monitoring has been utilized as a cost-effective alternative to inpatient video-EEG monitoring for non-surgical diagnostic evaluation of symptoms suggestive of epileptic seizures. We aimed to assess incidence of epileptiform discharges in ambulatory video-EEG recordings according to seizure symptom history obtained during clinical evaluation. METHODS: This was a retrospective cohort study. We queried seizure symptoms from 9,221 consecutive ambulatory video-EEG studies in 35 states over one calendar year. We assessed incidence of epileptiform discharges for each symptom, including symptoms that conformed to a category heading, even if not included in the ILAE 2017 symptom list. We report incidences, odds ratios, and corresponding p values using Fisher's exact test and univariate logistic regression. We applied multivariable logistic regression to generate odds ratios for the six symptom categories that are controlled for the presence of other symptoms. RESULTS: History that included motor symptoms (OR=1.53) or automatisms (OR=1.42) was associated with increased occurrence of epileptiform discharges, whereas history of sensory symptoms (OR=0.76) predicted lack of epileptiform discharges. Patient-reported symptoms that were associated with increased occurrence of epileptiform discharges included lip-smacking, moaning, verbal automatism, aggression, eye-blinking, déjà vu, muscle pain, urinary incontinence, choking and jerking. On the other hand, auditory hallucination memory deficits, lightheadedness, syncope, giddiness, fibromyalgia and chronic pain predicted absence of epileptiform discharges. The majority of epileptiform discharges consisted only of interictal sharp waves or spikes. CONCLUSIONS: Our study shows that the use of ILAE 2017 symptom categories may help guide ambulatory video-EEG studies.
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Eletroencefalografia/estatística & dados numéricos , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Monitorização Ambulatorial/estatística & dados numéricos , Convulsões/diagnóstico , Convulsões/fisiopatologia , Adulto , Idoso , Epilepsia/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Monitorização Neurofisiológica/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Convulsões/epidemiologia , Autorrelato/estatística & dados numéricos , Gravação em VídeoRESUMO
Rituximab (RTX) is a chimeric B-cell-depleting monoclonal antibody against CD-20 positive cells that has been approved for the induction and maintenance of granulomatosis with polyangiitis (GPA). Reports have identified RTX to cause drug-related psoriasis. Many theories of underlying pathways have been proposed. However, further workup around the mechanism and treatment is required. Here, we present a 38-year-old woman known to have GPA that developed drug-related psoriasis that was successfully treated with treatment discontinuation and starting adalimumab along with a literature review.
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PURPOSE: We evaluate outcome of in-home diagnostic ambulatory video-EEG monitoring (AVEM) performed on a nationwide cohort of patients over one calendar year, and we compare our findings with outcomes of inpatient adult and pediatric VEM performed during the same year at two academic epilepsy centers. METHODS: This is a retrospective cohort study. We obtained AVEM outcome data from an independent ambulatory-EEG testing facility. Inpatient VEM data from a 4-bed adult epilepsy center and an 8-bed pediatric epilepsy center were also included. Primary outcome measure was composite percentage of VEM records with epileptiform activity on EEG tracings or at least one video-recorded pushbutton event. We assessed patient-reported symptoms documented in AVEM event diaries. RESULTS: Of 9221 AVEM recordings performed across 28 states, 62.5% attained primary outcome. At least one patient-activated pushbutton event was captured on video in 54% of AVEM recordings (53.6% in adults, 56.1% in children). Epileptiform activity was reported in 1657 (18.0%) AVEM recordings (1473 [88.9%] only interictal, 9 [0.5%] only ictal, 175 [10.6%] both interictal and ictal). Most common patient-reported symptomatology during AVEM pushbutton events was behavioral/autonomic/emotional in adults and children. Compared to AVEM, inpatient VEM captured more confirmed representative events in adult and pediatric samples. CONCLUSIONS: AVEM is useful for non-urgent diagnostic evaluation of events.
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Eletroencefalografia/métodos , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Adolescente , Adulto , Idoso , Assistência Ambulatorial/métodos , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Avaliação de Resultados em Cuidados de Saúde , Estatísticas não Paramétricas , Estados Unidos/epidemiologia , Gravação em Vídeo , Adulto JovemRESUMO
BACKGROUND: Changes to the structure and function of the innervation of the gut contribute to symptom generation in inflammatory bowel diseases (IBD). However, delineation of the mechanisms of these effects has proven difficult. Previous work on sympathetic neurons identified interleukin (IL)-17A as a novel neurotrophic cytokine. Since IL-17A is involved in IBD pathogenesis, we tested the hypothesis that IL-17A contributes to neuroanatomical remodeling during IBD. METHODS: Immunohistochemistry for tyrosine hydroxylase was used to identify sympathetic axons in mice with dextran sulphate sodium (DSS)-induced colitis and controls. Axon outgrowth from sympathetic neurons in response to incubation in cytokines or endoscopic patient biopsy supernatants was quantified. KEY RESULTS: DSS-induced colitis led to an increase in tyrosine hydroxylase immunoreactivity in the inflamed colon but not the spleen. Colonic supernatants from mice with colitis and biopsy supernatants from Crohn's disease patients increased axon outgrowth from mouse sympathetic neurons compared to supernatants from uninflamed controls. An antibody that neutralized IL-17A blocked the ability of DSS-induced colitis and Crohn's disease supernatants to induce axon extension. CONCLUSIONS AND INFERENCES: These findings identify IL-17A as a potential mediator of neuroanatomical remodeling of the gut innervation during IBD.
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Colite/fisiopatologia , Doença de Crohn/fisiopatologia , Doenças Inflamatórias Intestinais/fisiopatologia , Interleucina-17/fisiologia , Plasticidade Neuronal , Sistema Nervoso Simpático/fisiopatologia , Adulto , Idoso , Axônios/fisiologia , Colite/induzido quimicamente , Colite/metabolismo , Colo/inervação , Colo/fisiopatologia , Doença de Crohn/metabolismo , Sulfato de Dextrana/administração & dosagem , Feminino , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Interleucina-17/administração & dosagem , Masculino , Pessoa de Meia-Idade , Baço/metabolismo , Baço/fisiopatologia , Fibras Simpáticas Pós-Ganglionares/fisiopatologia , Tirosina 3-Mono-Oxigenase/metabolismo , Adulto JovemRESUMO
Self-supported electrocatalysts are a new class of materials exhibiting high catalytic performance for various electrochemical processes and can be directly equipped in energy conversion devices. We present here, for the first time, sparse Au NPs self-supported on etched Ti (nanocarved Ti substrate self-supported with TiH2) as promising catalysts for the electrochemical generation of hydrogen (H2) in KOH solutions. Cleaned, as-polished Ti substrates were etched in highly concentrated sulfuric acid solutions without and with 0.1 M NH4F at room temperature for 15 min. These two etching processes yielded a thin layer of TiH2 (the corrosion product of the etching process) self-supported on nanocarved Ti substrates with different morphologies. While F--free etching process led to formation of parallel channels (average width: 200 nm), where each channel consists of an array of rounded cavities (average width: 150 nm), etching in the presence of F- yielded Ti surface carved with nanogrooves (average width: 100 nm) in parallel orientation. Au NPs were then grown in situ (self-supported) on such etched surfaces via immersion in a standard gold solution at room temperature without using stabilizers or reducing agents, producing Au NPs/TiH2/nanostructured Ti catalysts. These materials were characterized by scanning electron microscopy/energy-dispersive spectroscopy (SEM/EDS), grazing incidence X-ray diffraction (GIXRD), and X-ray photoelectron spectroscopy (XPS). GIXRD confirmed the formation of Au2Ti phase, thus referring to strong chemical interaction between the supported Au NPs and the substrate surface (also evidenced from XPS) as well as a titanium hydride phase of chemical composition TiH2. Electrochemical measurements in 0.1 M KOH solution revealed outstanding hydrogen evolution reaction (HER) electrocatalytic activity for our synthesized catalysts, with Au NPs/TiH2/nanogrooved Ti catalyst being the best one among them. It exhibited fast kinetics for the HER with onset potentials as low as -22 mV vs. RHE, high exchange current density of 0.7 mA cm-2, and a Tafel slope of 113 mV dec-1. These HER electrochemical kinetic parameters are very close to those measured here for a commercial Pt/C catalyst (onset potential: -20 mV, Tafel slope: 110 mV dec-1, and exchange current density: 0.75 mA cm-2). The high catalytic activity of these materials was attributed to the catalytic impacts of both TiH2 phase and self-supported Au NPs (active sites for the catalytic reduction of water to H2), in addition to their nanostructured features which provide a large-surface area for the HER.
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BACKGROUND: Health care is a basic human right, and Saudi Arabia affirms these rights for all its citizens. OBJECTIVES: To assess the knowledge of medical students regarding health rights in Saudi Arabia. METHODS: This cross-sectional study was conducted at King Abdulaziz University (KAU) from September 2015 through November 2015. A questionnaire written in English collected demographic data and included questions about reproductive health care and health rights of women and patients with cancer, senility, or special needs. RESULTS: Of the 267 participants, 184 (68.9%) were female, and 252 (94.4%) were Saudi. Regarding consent, 87 (32.6%) and 113 (42.3%) participants believed a female patient required the consent of a male guardian to receive medical treatment or surgery, respectively, in Saudi Arabia, and only 106 (39.7%) knew that a female patient could provide consent for a caesarean section. Sixty-six (24.7%) believed that abortion is never allowed in Islam. Only 93 (34.8%) were aware that acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) patients had health rights, about half (144, 53.9%) knew that cancer patients have a right to full information, and most (181, 67.8%) believed that a patient had the right to withhold health information from his/her family. Approximately half were aware that cancer patients have the right to free medical treatment (138, 51.7%) or that health rights applied to special needs patients (137, 51.3%) and senile patients (122, 45.7%). CONCLUSIONS: The knowledge of KAU medical students regarding health rights of certain patient populations highlights the importance of health rights education in medical school.
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Conhecimentos, Atitudes e Prática em Saúde , Direitos do Paciente , Estudantes de Medicina/psicologia , Estudos Transversais , Pessoas com Deficiência , Feminino , Humanos , Masculino , Neoplasias/terapia , Arábia Saudita , Faculdades de Medicina , Inquéritos e Questionários , Universidades , Saúde da Mulher , Adulto JovemRESUMO
In this paper, we demonstrated, for the first time, aluminum titania nanoparticle (Al-TiO2 NP) composites with variable amounts of TiO2 NPs as nonprecious active catalysts for the electrochemical generation of H2. These materials were synthesized by mixing desired amounts of hydrogen titanate nanotubes (TNTs), fabricated here by a cost-effective approach at moderate hydrothermal conditions, with aluminum powder (purity 99.7%; size 35 µm). The mixture was compacted under an applied uniaxial stress of 300 MPa followed by sintering at 500 °C for 1 h. After sintering had been completed, all TNTs were found to convert to TiO2 NPs (average particle size 15 nm). Finally, Al-xTiO2 NP nanocomposites (x = 1, 3, 5, and 10) were obtained and characterized by scanning electron microscopy/energy-dispersive X-ray, X-ray diffraction, and X-ray photoelectron spectroscopy. The hydrogen evolution reaction (HER) activity of these materials was studied in 0.5 M H2SO4 at 298 K using polarization and impedance measurements. The nanocomposite of chemical composition Al-5% TiO2 NPs showed the best catalytic performance for the HER, with an onset potential (EHER), a Tafel slope (ßc), and an exchange current density (j0) of -100 mV (RHE), 59.8 mV decade(-1), and 0.14 mA cm(-2), respectively. This HER activity is not far from that of the commercial platinum/carbon catalyst (EHER = 0.0 mV, ßc = 31 mV dec(-1), and j0 = 0.78 mA cm(-2)). The best catalyst also exhibited good stability after 10000 repetitive cycles with negligible loss in current.
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BACKGROUND AND PURPOSE: Endocannabinoids are a family of lipid mediators involved in the regulation of gastrointestinal (GI) motility. The expression, localization and function of their biosynthetic enzymes in the GI tract are not well understood. Here, we examined the expression, localization and function of the enzyme diacylglycerol lipase-α (DAGLα), which is involved in biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). EXPERIMENTAL APPROACH: Cannabinoid CB1 receptor-deficient, wild-type control and C3H/HeJ mice, a genetically constipated strain, were used. The distribution of DAGLα in the enteric nervous system was examined by immunohistochemistry. Effects of the DAGL inhibitors, orlistat and OMDM-188 on pharmacologically induced GI hypomotility were assessed by measuring intestinal contractility in vitro and whole gut transit or faecal output in vivo. Endocannabinoid levels were measured by mass spectrometry. KEY RESULTS: DAGLα was expressed throughout the GI tract. In the intestine, unlike DAGLß, DAGLα immunoreactivity was prominently expressed in the enteric nervous system. In the myenteric plexus, it was colocalized with the vesicular acetylcholine transporter in cholinergic nerves. In normal mice, inhibiting DAGL reversed both pharmacologically reduced intestinal contractility and pharmacologically prolonged whole gut transit. Moreover, inhibiting DAGL normalized faecal output in constipated C3H/HeJ mice. In colons incubated with scopolamine, 2-AG was elevated while inhibiting DAGL normalized 2-AG levels. CONCLUSIONS AND IMPLICATIONS: DAGLα was expressed in the enteric nervous system of mice and its inhibition reversed slowed GI motility, intestinal contractility and constipation through 2-AG and CB1 receptor-mediated mechanisms. Our data suggest that DAGLα inhibitors may be promising candidates for the treatment of constipation.
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Ácidos Araquidônicos/biossíntese , Constipação Intestinal/tratamento farmacológico , Endocanabinoides/biossíntese , Glicerídeos/biossíntese , Lipase Lipoproteica/antagonistas & inibidores , Receptor CB1 de Canabinoide/metabolismo , Animais , Constipação Intestinal/genética , Constipação Intestinal/fisiopatologia , Motilidade Gastrointestinal/efeitos dos fármacos , Isoleucina/análogos & derivados , Isoleucina/farmacologia , Lactonas/farmacologia , Lipase Lipoproteica/metabolismo , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Orlistate , Escopolamina/farmacologiaRESUMO
BACKGROUND: Proteases play a major role in inflammatory diseases of the gastrointestinal tract. Activatable probes are a major technological advance, enabling sensitive detection of active proteases in tissue samples. Our aim was to synthesize an activatable probe for cathepsin S and validate its use in a mouse model of colitis. METHODS: We designed and synthesized a new fluorescent activatable probe, NB200, for the detection of active cathepsin S. Colitis was induced in C57BL/6 mice by the administration of 3% dextran sulfate sodium (DSS). Homogenized mouse colons, with or without the addition of the specific cathepsin S inhibitor MV026031, were incubated with NB200 in a fluorescent plate reader. KEY RESULTS: NB200 selectively detected purified cathepsin S and not other common inflammatory proteases. Homogenates of colon from mice with DSS colitis induced a significant fluorescent increase when compared to control animals (control vs DSS: p < 0.05 at 200 min and p < 0.01 at 220-240 min), indicating cathepsin S activation. The cathepsin S inhibitor abolished this increase in fluorescence (DSS vs DSS + MV026031: p < 0.05 at 140 min, p < 0.01 at 180 min, p < 0.001 at 200-240 min), which confirms cathepsin S activation. Cathepsin S activity correlated with the disease activity index (Spearman r = 0.77, p = 0.017). CONCLUSIONS & INFERENCES: Our investigation has demonstrated the utility of activatable probes for detecting protease activity in intestinal inflammation. Panels of such probes may allow 'signature' protease profiles to be established for a range of inflammatory diseases and disorders.
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Catepsinas/análise , Colite/enzimologia , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacologia , Animais , Colite/induzido quimicamente , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The enteric nervous system is composed of both enteric neurones and enteric glia. Enteric glial cells were first described by Dogiel and are now known to outnumber neurones approximately 4 : 1. In the past, these cells were assumed to subserve a largely supportive role; however, recent evidence indicates that enteric glial cells may play a more active role in the control of gut function. In transgenic mouse models, where enteric glial cells are selectively ablated, the loss of glia results in intestinal inflammation and disruption of the epithelial barrier. Enteric glia are activated specifically by inflammatory insults and may contribute actively to inflammatory pathology via antigen presentation and cytokine synthesis. Enteric glia also express receptors for neurotransmitters and so may serve as intermediaries in enteric neurotransmission. Thus, enteric glia may serve as a link between the nervous and immune systems of the gut and may also have an important role in maintaining the integrity of the mucosal barrier and in other aspects of intestinal homeostasis.