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OBJECTIVE: In epilepsy, early diagnosis, accurate determination of epilepsy type, proper selection of antiseizure medication, and monitoring are all essential. However, despite recent therapeutic advances and conceptual reconsiderations in the classification and management of epilepsy, serious gaps are still encountered in day-to-day practice in Egypt as well as several other resource-limited countries. Premature mortality, poor quality of life, socio-economic burden, cognitive problems, poor treatment outcomes, and comorbidities are major challenges that require urgent actions to be implemented at all levels. In recognition of this, a group of Egyptian epilepsy experts met through a series of consecutive meetings to specify the main concepts concerning the diagnosis and management of epilepsy, with the ultimate goal of establishing a nationwide Egyptian consensus. METHODS: The consensus was developed through a modified Delphi methodology. A thorough review of the most recent relevant literature and international guidelines was performed to evaluate their applicability to the Egyptian situation. Afterward, several remote and live rounds were scheduled to reach a final agreement for all listed statements. RESULTS: Of 278 statements reviewed in the first round, 256 achieved ≥80% agreement. Live discussion and refinement of the 22 statements that did not reach consensus during the first round took place, followed by final live voting then consensus was achieved for all remaining statements. SIGNIFICANCE: With the implementation of these unified recommendations, we believe this will bring about substantial improvements in both the quality of care and treatment outcomes for persons with epilepsy in Egypt. PLAIN LANGUAGE SUMMARY: This work represents the efforts of a group of medical experts to reach an agreement on the best medical practice related to people with epilepsy based on previously published recommendations while taking into consideration applicable options in resource-limited countries. The publication of this document is expected to minimize many malpractice issues and pave the way for better healthcare services on both individual and governmental levels.
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Consenso , Técnica Delphi , Epilepsia , Humanos , Egito , Epilepsia/terapia , Epilepsia/diagnóstico , Guias de Prática Clínica como Assunto , Gerenciamento Clínico , Anticonvulsivantes/uso terapêuticoRESUMO
INTRODUCTION: There is little data on the role of endovascular treatment (EVT) of cerebral venous sinus thrombosis (CVST) due to vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe clinical characteristics and outcomes of CVST-VITT patients who were treated with EVT. PATIENTS AND METHODS: We report data from an international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 6 March 2023. VITT was defined according to the Pavord criteria. RESULTS: EVT was performed in 18/136 (13%) patients with CVST-VITT (92% aspiration and/or stent retrieval, 8% local thrombolysis). Most common indications were extensive thrombosis and clinical or radiological deterioration. Compared to non-EVT patients, those receiving EVT had a higher median thrombus load (4.5 vs 3). Following EVT, local blood flow was improved in 83% (10/12, 95% confidence interval [CI] 54-96). One (6%) asymptomatic sinus perforation occurred. Eight (44%) patients treated with EVT also underwent decompressive surgery. Mortality was 50% (9/18, 95% CI 29-71) and 88% (8/9, 95% CI 25-66) of surviving EVT patients achieved functional independence with a modified Rankin Scale score of 0-2 at follow-up. In multivariable analysis, EVT was not associated with increased mortality (adjusted odds ratio, 0.66, 95% CI 0.16-2.58). DISCUSSION AND CONCLUSION: We describe the largest cohort of CVST-VITT patients receiving EVT. Half of the patients receiving EVT died during hospital admission, but most survivors achieved functional independence.
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Púrpura Trombocitopênica Idiopática , Trombose dos Seios Intracranianos , Trombocitopenia , Vacinas , Humanos , Vacinas contra COVID-19/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombose dos Seios Intracranianos/etiologiaRESUMO
OBJECTIVE: The current clinical trial was conducted to evaluate the effect of proximal indirect restorations in endodontically treated posterior teeth with deeply located margins following deep margin elevation compared to surgical crown lengthening. MATERIAL AND METHODS: Deep proximal cavities in endodontically treated posterior teeth were randomly assigned into two groups; deep margin elevation (DME) or crown lengthening (CL). The clinical attachment level (CAL), probing depth (PD), bleeding on probing (BOP), crestal bone level (CBL), and secondary caries were evaluated at the baseline, 1, 3, 6, 9, and 12 months. RESULTS: A total of 20 proximal cavities were included in the study; there was no significant difference between the two groups regarding mean CAL values at the baseline and 1 month, while there was a significant difference between the two groups in all other periods. Regarding the PD, there was no statistical significance between the two groups except at 9 and 12 months, where CL showed higher mean PD values than DME. There was no statistically significant difference in BOP or CBL between the two groups. CONCLUSIONS: DME and CL are considered clinically successful with favorable biologic responses. CLINICAL RELEVANCE: The deep margin elevation approach could provide a more conservative solution when relocating deeply seated cervical margins in a more coronal position. DME reduced the number of visits and time needed for the restoration of endodontically treated teeth. Surgical crown lengthening remains a gold standard procedure in the re-establishment of the supracrestal tissue attachment, especially in cases where cervical margins are beyond the elevation capacity.
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Cárie Dentária , Dente não Vital , Humanos , Aumento da Coroa Clínica , PescoçoRESUMO
An acute exposure study of mancozeb (MAZ) fungicide was applied on Oreochromis niloticus for 96-h duration. Three hundred fish (20.50 ± 1.60 g) were assigned into six groups (50 fish/ group; 10 fish/replicate) and exposed to different six concentrations (0, 4, 8, 12, 16, and 20 mg L-1) of MAZ for 96-h. The Probit analysis program was used to compute the 96-h lethal concentration 50 (96-h LC50) of MAZ. During the exposure duration, the fish's behavior, clinical symptoms, and mortalities were recorded daily. After the exposure period was ended, the hematological, biochemical, immunological, and oxidant/antioxidant parameters were evaluated. The results of this study recorded the 96-h LC50 of MAZ for O. niloticus to be 11.49 mg L-1. Acute MAZ exposure badly affected the fish's behavior in the form of increased the breath gasping and swimming activity with aggressive mode. The exposed fish showed excessive body hemorrhages and fin rot. The survival rate of the exposed fish to MAZ was 100, 80, 66, 50, 38, and 30% in 0, 4, 8, 12, 16, and 20 mg L-1 MAZ, respectively. The hematological indices (red blood cell count, hemoglobin, packed cell volume%, and white blood cell count) were significantly decreased by increasing the MAZ exposure concentration (8-20 mg L-1). The acetylcholine esterase activity and immune indices (lysozyme, nitric oxide, immunoglobulin M, complement 3) were decreased by MAZ exposure (4-20 mg L-1). Acute MAZ exposure induced hepato-renal dysfunction and elevated stress-related parameter (cortisol) by increasing the MAZ concentration. A significant reduction in the antioxidant parameters (total antioxidant activity, catalase, and superoxide dismutase) with increasing the lipid peroxidation marker (malondialdehyde) was noticed by acute MAZ exposure (4 -20 mg L-1) in O. niloticus. Based on these outcomes, the MAZ exposure induced toxicity to the fish evident in changes in fish behavior, neurological activity, hepato-renal functioning, and immune-antioxidant responses which suggest physiological disruption.
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Ciclídeos , Fungicidas Industriais , Poluentes Químicos da Água , Animais , Antioxidantes/metabolismo , Fungicidas Industriais/toxicidade , Ciclídeos/fisiologia , Etologia , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo , Dieta , Suplementos Nutricionais/análise , Ração Animal/análiseRESUMO
BACKGROUND: Paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs) have been posited as markers of chronic active lesions (CALs). OBJECTIVE: To assess the lesion-level concordance of PRLs and SELs in MS and to characterize changes in brain tissue integrity in CALs over time. METHODS: MRIs were analyzed from a substudy of AFFINITY [NCT03222973], a phase 2 trial of opicinumab in relapsing MS. Assessments included (1) identification of SELs based on longitudinal MRIs over 72 weeks, and identification of PRLs on susceptibility-weighted imaging (SWI) filtered phase images at week 72; (2) evaluation of subject-level correlation of SEL and PRL counts, volumes, and degree of lesion-level overlap between SELs and PRLs; and (3) characterization of tissue integrity over time in overlapping and non-overlapping SELs and PRLs. RESULTS: In 41 subjects, 119 chronic PRLs and 267 SELs were detected. Of 119 (39.5%) chronic PRLs, 47 co-localized with a SEL; 46/267 (17.2%) SELs co-localized with a PRL. PRLs co-localized with SELs showed expansion and worsening microstructural damage over time. SELs with and without co-localization with PRLs showed ongoing tissue damage. CONCLUSIONS: Chronic MS lesions identified as both PRL and SEL were associated with the most severe accumulation of tissue damage. TRIAL REGISTRATION: AFFINITY [NCT03222973].
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Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética , Estudos LongitudinaisRESUMO
Rapidly progressive dementia is an uncommon neurological presentation and usually needs extensive workup, especially for reversible causes. Dural arteriovenous fistula (DAVF) has been rarely reported as a cause of thalamic dementia, in which bilateral thalamic venous congestion and edema cause dementia that usually progresses rapidly. We present a case of a 45 years-old male who presented with rapidly progressive severe attention and memory impairment over one week. Initial work-up showed bilateral thalamic recent venous infarctions and edema. Extensive work-up revealed an intracranial DAVF with internal deep venous thrombosis. Management with endovascular treatment of DAVF followed by anticoagulation for venous thrombosis leads to improvement of the patient's clinical condition, particularly memory and attention. In conclusion, DAFV could present with thalamic rapidly progressive dementia due to bithalamic infarctions and edema. Early diagnosis and treatment will reverse the cause and improve the patient's general and cognitive conditions.
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BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.
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Vacinas contra COVID-19 , COVID-19 , Trombose Intracraniana , Trombocitopenia , Trombose , Vacinas , Trombose Venosa , Adulto , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Hemorragia Cerebral , Feminino , Humanos , Trombose Intracraniana/diagnóstico , Masculino , Fatores de Risco , SARS-CoV-2RESUMO
COVID-19 is a pandemic disease caused by SARS-CoV-2, which is an RNA virus similar to the hepatitis C virus (HCV) in the replication process. Sofosbuvir/ledipasvir is an approved drug to treat HCV infection. This study investigates the efficacy of Sofosbuvir/ledipasvir as a treatment for patients with moderate COVID-19 infection. This is a single-blinded parallel-randomized controlled trial. The participants were randomized equally into the intervention group that received Sofosbuvir/ledipasvir (S.L. group), and the control group received Oseltamivir, Hydroxychloroquine, and Azithromycin (OCH group). The primary outcomes were the cure rate over time and the incidence of serious adverse events. The secondary outcomes included the laboratory findings. 250 patients were divided equally into each group. Both groups were similar regarding gender, but age was higher in the S.L. group (p=0.001). In the S.L. group, 89 (71.2%) patients were cured, while only 51 (40.8%) patients were cured in the OCH group. The cure rate was significantly higher in the S.L. group (RR=1.75, p<0.001). Kaplan-Meir plot showed a considerably higher cure over time in the S.L. group (Log-rank test, p=0.032). There were no deaths in the S.L. group, but there were six deaths (4.8%) in the OCH group (RR=0.08, p=0.013). Seven patients (5.6%) in the S.L. group and six patients (4.8%) in the OCH group were admitted to the intensive care unit (ICU) (RR=1.17, P=0.776). There were no significant differences between treatment groups regarding total leukocyte and neutrophils count, lymph, and urea. Sofosbuvir/ledipasvir is suggestive of being effective in treating patients with moderate COVID-19 infection. Further studies are needed to compare Sofosbuvir/ledipasvir with new treatment protocols.
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Tratamento Farmacológico da COVID-19 , Hepatite C Crônica , Hepatite C , Antivirais/farmacologia , Antivirais/uso terapêutico , Benzimidazóis , Quimioterapia Combinada , Egito , Fluorenos , Genótipo , Hepacivirus , Hepatite C Crônica/tratamento farmacológico , Humanos , Ribavirina/efeitos adversos , SARS-CoV-2 , Sofosbuvir/farmacologia , Sofosbuvir/uso terapêutico , Resultado do Tratamento , Uridina Monofosfato/efeitos adversosRESUMO
PURPOSE: Neurological sequelae after COVID-19 vaccination are rare. We investigated the possible pathogenesis behind the development of neurological complications within a short period after Saudi residents received a COVID-19 vaccine. PATIENTS AND METHODS: We evaluated 18 patients who recently received a COVID-19 vaccine (Comirnaty and Vaxzevria vaccines) and presented with neurological complications to the Saudi German Hospitals in Jeddah, Saudi Arabia. Neurologists assessed the patients' clinical presentation, radiological investigations, and laboratory findings. RESULTS: Three patients who received the first dose of the Vaxzevria vaccine experienced severe cerebral venous thrombosis, two of them were complicated by intracranial hemorrhage. Their laboratory investigations showed very high d-dimers and severe thrombocytopenia, which have been linked to higher mortality and poor outcome. Ischemic stroke occurred in eight cases (44.4%) with a predominance in older male patients. Three patients presented with seizures, two had optic neuritis. Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) occurred in two male patients following vaccination with Comirnaty. CONCLUSION: Neurological complications after COVID-19 vaccinations are very rare, and only a few cases have been reported worldwide. The shared pathophysiological basis between COVID-19 viral infection and COVID-19 vaccines stands behind the very rare neurological complications resulting from the hypercoagulable state triggered by the general inflammatory condition. We suspect some differences in the pathogenesis of ischemic stroke caused by COVID-19 infection and COVID-19 vaccines, which render COVID-19 vaccine-associated ischemic stroke more responsive to treatment. To date, no definitive association between the vaccine and GBS has been proven by any strong evidence, but it has recently been added as a very rare side effect of the Janssen COVID-19 vaccine. No possible links of Miller Fisher syndrome to COVID-19 vaccines have been reported before the one reported in this study.
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BACKGROUND: Major disparities have been reported in recombinant tissue plasminogen activator (rtPA) availability among countries of different socioeconomic status. AIMS: To characterize variability of rtPA price, its availability, and its association with and impact on each country's health expenditure (HE) resources. METHODS: We conducted a global survey to obtain information on rtPA price (50 mg vial, 2020 US Dollars) and availability. Country-specific data, including low, lower middle (LMIC), upper middle (UMIC), and high-income country (HIC) classifications, and gross domestic product (GDP) and HE, both nominally and adjusted for purchasing power parity (PPP), were obtained from World Bank Open Data. To assess the impact of rtPA cost, we computed the rtPA price as percentage of per capita GDP and HE and examined its association with the country income classification. RESULTS: rtPA is approved and available in 109 countries. We received surveys from 59 countries: 27 (46%) HIC, 20 (34%) UMIC, and 12 (20%) LMIC. Although HIC have significantly higher per capita GDP and HE compared to UMIC and LMIC (p < 0.0001), the median price of rtPA is non-significantly higher in LMICs (USD 755, interquartile range, IQR (575-1300)) compared to UMICs (USD 544, IQR (400-815)) and HICs (USD 600, IQR (526-1000)). In LMIC, rtPA cost accounts for 217.4% (IQR, 27.1-340.6%) of PPP-adjusted per capita HE, compared to 17.6% (IQR (11.2-28.7%), p < 0.0001) for HICs. CONCLUSION: We documented significant variability in rtPA availability and price among countries. Relative costs are higher in lower income countries, exceeding the available HE. Concerted efforts to improve rtPA affordability in low-income settings are necessary.
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Acidente Vascular Cerebral , Ativador de Plasminogênio Tecidual , Humanos , Ativador de Plasminogênio Tecidual/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Custos e Análise de Custo , Produto Interno Bruto , Terapia TrombolíticaRESUMO
OBJECTIVE: To study the combined effect of modified genioglossus advancement (MGGA) and radiofrequency tongue base reduction (RFTBR) a long with anterolateral advancement (ALA) pharyngolplasty on OSA patients with retrolingual airway collapse. STUDY DESIGN: Prospective clinical study. SETTING: Zagazig and Benha Universities Medical Hospitals. PATIENTS AND METHODS: Twenty-one patients (21)with multilevel OSA underwent modified genioglossus advancement with radiofrequency tongue base reduction and anterolateral advancement pharyngolplasty. All patients were assessed before and 6 months after surgery by history talking, clinical examination, Epworth Sleepiness Scale evaluation fiberoptic examination during muller's maneuver, drug induced sleep endoscopy (DISE), panoramic X-ray, Cephalometry and polysomnography. RESULTS: Postoperative mean ± SD Epworth Sleepiness Scale (ESS) significantly decreased from 18.86 ± 2.03to 8.19 ± 1.86 (P-value was <0.001 95% (CI) 9.80 to 11.53).postoperative mean ± SD AHI decreased from 53.39 ± 14.10 to 26.66 ± 5.44 (P-value was <0.001 95% CI 22.37 to 32.81), postoperative mean ± SD LOS increased from 68.33 ± 9.12 to 86.0 ± 4.96 (P-value was <0.001 95% (CI) 15.24 to21.33).Based on cephalometric analysis postoperative mean ± SD PAS at mid retrolingual point in mm increased from 6.43 ± 1.25 to 11.98 ± 1.69 (P-value was <0.001 95% (CI) 4.78 to 6.32), also postoperative mean ± SD Distance between H-MP in mm decreased from 23.38 ± 1.14 to 15.17 ± 0.97 (P-value was 0.001 95% (CI) 7.66 to 8.76).The postoperative mean ± SD distance from hyoid to menton (H-me) in mm decreased from 39.47 ± 2.37to24.83 ± 2.43(P-value was 0.001 95% (CI) 7.31 to 8.41), the mean ± SD distance of genioglossus muscle advancement in mm was 14.45 ± 1.12.With a success rate defined as AHI < 20 and/or 50% reduction in AHI of the pre- operative value, the surgical success was 81%. CONCLUSION: MGGA with RFTBR along with anterolateral advancement pharyngoplasty in a single session is well tolerated and safe surgery in the treatment of multilevel OSA patients. It is effective in reducing respiratory parameters and subjective symptoms of OSA.
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Apneia Obstrutiva do Sono , Cefalometria , Humanos , Polissonografia , Estudos Prospectivos , Apneia Obstrutiva do Sono/cirurgia , Língua/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Cisplatin, an effective drug against cancer, commonly induces nephrotoxicity; limiting its therapeutic efficacy and application. In this study, Cisplatin NanoComposite (Cis NC) was formulated successfully from irradiated chitosan coated Cisplatin and MgO nanoparticles (CHIT/Cis/MgO NPs) to promote cisplatin release in a more sustained manner to improve therapeutic efficacy via the reduction of its nephrotoxicity. To compare the relative induced renal toxicity of cisplatin with Cisplatin NanoComposite, histological and biochemical mechanisms underlying nephrotoxicity were investigated. METHODS: Thirty rats were equally separated to three groups, first group received saline injections and adjusted as the control group, the second group was injected intra-peritoneal with cisplatin 0.64 mg/kg b. wt./day for 6 weeks, the third group was injected intra-peritoneal with Cis NC 5.75 mg/kg b. wt. daily for 6 weeks. RESULTS: Cisplatin-induced renal functional impairment and histopathological damages in the kidney; also, cisplatin disrupted the balance of the redox system in renal tissue, stimulated the inflammatory reactions in the kidney via triggering signal transducer and activator of transcription-1 (STAT1) dependent pathways. Moreover, Cisplatin-induced activation of mammalian target of rapamycin mTOR and inactivation of AMPK/PI3K/Akt signal pathway, and was coupled with induction of p53 activity and the executioner caspase3 to induce apoptotic renal cell death. On the other hand, Cis NC exerted a minimal stimulatory effect on apoptotic and inflammatory signal cascade with negligible renal functional and morphological alterations. CONCLUSION: We postulated that Cis NC may be a valued possible drug to decrease the cytotoxicity of cisplatin thus reserves the renal function and structure.
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Cisplatino , Nefropatias , Rim , Óxido de Magnésio/farmacologia , Nanocompostos , Transdução de Sinais/efeitos dos fármacos , Quinases Proteína-Quinases Ativadas por AMP/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Cisplatino/toxicidade , Desenvolvimento de Medicamentos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/prevenção & controle , Testes de Função Renal , Nanocompostos/administração & dosagem , Nanocompostos/química , Fosfatidilinositol 3-Quinases/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Fator de Transcrição STAT1/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
AIM: This work aims to investigate the possible radio-adaptive mechanisms induced by low-dose (LD) whole-body γ-irradiation alone or combined with alpha-lipoic acid (ALA) administration in modulating high-dose (HD) head irradiation-induced brain injury in rats. MATERIALS AND METHODS: Rats were irradiated with LD (.25 Gy) 24 hours prior HD (20 Gy), and subjected to ALA (100 mg/kg/day) 5 minutes after HD and continued for 10 days. At the end of the experiment, animals were sacrificed and brain samples were dissected for biochemical and histopathological examinations. RESULTS: HD irradiation-induced brain injury as manifested by elevation of oxidative stress, DNA damage, apoptotic, and inflammatory markers in brain tissue. Histological examination of brain sections showed marked alterations. However, LD alone or combined with ALA ameliorated the changes induced by HD. CONCLUSION: Under the present experimental conditions, LD whole-body irradiation exhibited neuroprotective activity against detrimental effects of a subsequent HD head irradiation. This effect might be due to the adaptive response induced by LD that activated the anti-oxidative, anti-apoptotic, and anti-inflammatory mechanisms in the affected animals making them able to cope with the subsequent high-dose exposure. However, the combined LD exposure and ALA supplementation produced a further modulating effect in the HD-irradiated rats.
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BACKGROUND: Wave-CAIPI Visualization of Short Transverse relaxation time component (ViSTa) is a recently developed, short-T1-sensitized MRI method for fast quantification of myelin water fraction (MWF) in the human brain. It represents a promising technique for the evaluation of subtle, early signals of demyelination in the cerebral white matter of multiple sclerosis (MS) patients. Currently however, few studies exist that robustly assess the utility of ViSTa MWF measures of myelin compared to more conventional MRI measures of myelin in the brain of MS patients. Moreover, there are no previous studies evaluating the sensitivity of ViSTa MWF for the non-invasive detection of subtle tissue damage in both normal-appearing white matter (NAWM) and white matter lesions of MS patients. As a result, a central purpose of this study was to systematically evaluate the relationship between myelin sensitivity of T1-based ViSTa MWF mapping and a more generally recognized metric, Magnetization Transfer Saturation (MTsat), in healthy control and MS brain white matter. METHODS: ViSTa MWF and MTsat values were evaluated in automatically-classified normal appearing white matter (NAWM), white matter (WM) lesion tissue, cortical gray matter, and deep gray matter of 29 MS patients and 10 healthy controls using 3T MRI. MWF and MT sat were also assessed in a tract-specific manner using the Johns Hopkins University WM atlas. MRI-derived measures of cerebral myelin content were uniquely compared by employing non-normal distribution-specific measures of median, interquartile range and skewness. Separate analyses of variance were applied to test tissue-specific differences in MTsat and ViSTa MWF distribution metrics. Non-parametric tests were utilized when appropriate. All tests were corrected for multiple comparisons using the False Discovery Rate method at the level, α=0.05. RESULTS: Differences in whole NAWM MS tissue damage were detected with a higher effect size when using ViSTa MWF (q = 0.0008; Æ2 = 0.34) compared to MTsat (q = 0.02; Æ2= 0.24). We also observed that, as a possible measure of WM pathology, ViSTa-derived NAWM MWF voxel distributions of MS subjects were consistently skewed towards lower MWF values, while MTsat voxel distributions showed reduced skewness values. We further identified tract-specific reductions in mean ViSTa MWF of MS patients compared to controls that were not observed with MTsat. However, MTsat (q = 1.4 × 10-21; Æ2 = 0.88) displayed higher effect sizes when differentiating NAWM and MS lesion tissue. Using regression analysis at the group level, we identified a linear relationship between MTsat and ViSTa MWF in NAWM (R2 = 0.46; p = 7.8 × 10-4) lesions (R2 = 0.30; p = 0.004), and with all tissue types combined (R2 = 0.71; p = 8.4 × 10-45). The linear relationship was also observed in most of the WM tracts we investigated. ViSTa MWF in NAWM of MS patients correlated with both disease duration (p = 0.02; R2 = 0.27) and WM lesion volume (p = 0.002; R2 = 0.34). CONCLUSION: Because ViSTa MWF and MTsat metrics exhibit differential sensitivities to tissue damage in MS white matter, they can be collected in combination to provide an efficient, comprehensive measure of myelin water and macromolecular pool proton signals. These complementary measures may offer a more sensitive, non-invasive biopsy of early precursor signals in NAWM that occur prior to lesion formation. They may also aid in monitoring the efficacy of remyelination therapies.
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Esclerose Múltipla , Substância Branca , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Esclerose Múltipla/diagnóstico por imagem , Bainha de Mielina , Água , Substância Branca/diagnóstico por imagemRESUMO
Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. Main Outcomes and Measures: Clinical characteristics and mortality rate. Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.
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Vacinas contra COVID-19/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade , Sistema de Registros , Trombose dos Seios Intracranianos/mortalidade , Trombocitopenia/mortalidade , Tromboembolia Venosa/mortalidade , Ad26COVS1 , Adulto , Idoso , Vacina BNT162 , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Estudos de Coortes , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Fatores Sexuais , Trombose dos Seios Intracranianos/sangue , Trombose dos Seios Intracranianos/induzido quimicamente , Síndrome , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Tromboembolia Venosa/sangue , Tromboembolia Venosa/induzido quimicamente , Adulto JovemRESUMO
BACKGROUND: The optimal strategy for revascularization in patients with NSTEACS who had multivessel coronary artery disease. A lack of evidence exists about the role of complete coronary revascularization by PCI in patients with non-ST segment elevation acute coronary syndrome (NSTEACS). Till now, ACC/AHA and ESC guidelines are not clear regarding the optimal strategy for revascularization in NSTEACS patients with multivessel coronary artery disease. In this setting, identification of the culprit lesion by angiography only could be challenging. The objective is to compare the hospital and short-term (6 months) outcomes of 3 different coronary revascularization strategies in NSTEACS patients with and multivessel coronary artery disease. RESULTS: Our study was a prospective study that included 90 patients who presented with acute chest pain and were diagnosed with NSTEACS. The patients were divided into 3 groups according to the plan of management: total revascularization group (total group), staged revascularization group (staged group), and functional revascularization group using FFR (FFR group). We studied the effect of demographic data, risk factors, and angiographic and procedural criteria on hospital and short-term outcomes. No significant statistical difference was seen among the three groups regarding the hospital outcome (in-stent thrombosis, unstable angina, and renal impairment). Also, the short-term (after 6 months) outcome regarding myocardial infarction, hospitalization, stroke, and cardiac death did not differ significantly between the three groups. CONCLUSIONS: Considering NSTEACS patients with multivessel disease, different coronary revascularization strategies (total, staged, or FFR) are comparable regarding immediate and short-term (6 months) clinical follow-up. FFR can change the preplanned management, and less number of stents per patient is needed when FFR is utilized.
RESUMO
Multimodal neuroimaging provides a rich source of data for identifying brain regions associated with disease progression and aging. However, present studies still typically analyze modalities separately or aggregate voxel-wise measurements and analyses to the structural level, thus reducing statistical power. As a central example, previous works have used two quantitative MRI parameters-R2* and quantitative susceptibility (QS)-to study changes in iron associated with aging in healthy and multiple sclerosis subjects, but failed to simultaneously account for both. In this article, we propose a unified framework that combines information from multiple imaging modalities and regularizes estimates for increased interpretability, generalizability, and stability. Our work focuses on joint region detection problems where overlap between effect supports across modalities is encouraged but not strictly enforced. To achieve this, we combine L 1 (lasso), total variation (TV), and L 2 group lasso penalties. While the TV penalty encourages geometric regularization by controlling estimate variability and support boundary geometry, the group lasso penalty accounts for similarities in the support between imaging modalities. We address the computational difficulty in this regularization scheme with an alternating direction method of multipliers (ADMM) optimizer. In a neuroimaging application, we compare our method against independent sparse and joint sparse models using a dataset of R2* and QS maps derived from MRI scans of 113 healthy controls: our method produces clinically-interpretable regions where specific iron changes are associated with healthy aging. Together with results across multiple simulation studies, we conclude that our approach identifies regions that are more strongly associated with the variable of interest (e.g., age), more accurate, and more stable with respect to training data variability. This work makes progress toward a stable and interpretable multimodal imaging analysis framework for studying disease-related changes in brain structure and can be extended for classification and disease prediction tasks.
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For the treatment of internal and external hemorrhoids, policresulen (POL) and cinchocaine hydrochloride (CIN) are used in combination. Using a new, simple, fast, and economical first-derivative synchronous fluorescence spectroscopic process, both drugs were simultaneously determined and validated. At Δλ60 nm and with a scanning rate of 600 nm/min, methanol was used as the solvent for both products. In the concentration ranges of 5.0-21.0 µg mL-1 and 0.5-6.0 µg mL-1 for POL and CIN, the amplitude-concentration plots were rectilinear. The detection limits were found to be 0.770 µg mL-1 and 0.118 µg mL-1 and the quantitation limits for POL and CIN were 2.541 µg mL-1 and 0.391 µg mL-1. To evaluate all compounds in synthetic mixtures and medicinal dosage types, the proposed method has been successfully applied. These findings were in line with the results obtained using high-performance thin layer chromatography, the comparison process.
Assuntos
Dibucaína , Cresóis , Combinação de Medicamentos , Formaldeído , Pomadas , Espectrometria de Fluorescência , SupositóriosRESUMO
Metastatic tumors to the choroid are the most common intraocular malignancies. Choroidal metastasis from lung cancer is uncommon. Visual affection or other ocular manifestations as the initial clinical presentation of lung cancer primarily are rare. We report a case of a 71-year-old female patient presented with eye floaters in her right eye. Examination of the right eye visual acuity of 20/30 and fundoscopy revealed a pale choroidal mass superior to optic disc. Ocular coherent tomography showed subretinal fluid at the site of choroidal lesion. The patient is currently treated with radiotherapy and chemotherapy for secondary metastasizes in liver. In spite of floaters is very common nonserious symptoms in ophthalmology practice, but it should be taken seriously to rule out lifesaving condition.
Assuntos
Neoplasias da Coroide , Neoplasias Pulmonares , Idoso , Corioide , Neoplasias da Coroide/diagnóstico , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Oftalmoscopia , Acuidade VisualRESUMO
Multiple endocrine neoplasia type 1 (MEN1) is a complex, autosomal dominant inherited syndrome characterized by 3 different tumors (parathyroid, anterior pituitary, and pancreatic islet). The diagnosis is defined clinically by the presence of 2 or more primary tumors. We report the case of a 35 years old patient who presented with recurrent renal stones and imaging findings for MEN1. Computed tomography pancreas revealed a mass in the tail which was confirmed by magnetic resonance imaging. Ultrasound of her neck showed a mass on the left side and MIBI scan diagnosed a parathyroid adenoma which was later pathologically confirmed.