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Nigella sativa (NS), commonly known as black cumin or black seed, is a medicinal plant with a rich history of traditional use in various cultures. Recent research has shed light on its potential therapeutic properties, particularly its effects on endothelial markers involved in inflammatory processes. This systematic review and meta-analysis evaluated the endothelial function responses, including intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM), to NS supplementation. We systematically searched Medline via PubMed, Scopus, Web of Science, and Embase databases from inception until August 5, 2023. Comparative randomized controlled trials (RCTs) were included. Pairwise meta-analysis was conducted using RevMan version 5.4 for Windows. Pooled data were reported as mean difference (MD), with their 95% confidence interval (CI). The present meta-analysis included three RCTs, which included 146 patients. The pooled random-effect size showed no difference between the NS group and the control group in terms of ICAM (MD = -59.32, 95% CI: -137.18 to 18.54; p = 0.14) and VCAM (MD = -200.1, 95% CI: -429.9 to 29.69; p = 0.09). The pooled data were severely heterogeneous. In conclusion, NS supplementation does not have a significant impact on the endothelial function of patients with CVD or the risks of CVD. Further comparative RCTs with larger sample sizes and more diverse populations are needed to establish the efficacy and safety of NS in different clinical settings.
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Clinical Relevance: Visual function impairment from diabetic retinopathy can have a considerable impact on patient's quality of life. Best-corrected visual acuity (BCVA) is most commonly used to assess visual function and guide clinical trials. However, BCVA is affected late in the disease process, is not affected in early disease, and does not capture some of the visual disturbances described by patients with diabetes. The goal of this report is to evaluate the relationship between diabetic retinal disease (DRD) and visual function parameters to determine which if any of them may be used in a future DRD staging system. Methods: The visual functions working group was 1 of 6 areas of DRD studied as part of the DRD staging system update, a project of the Mary Tyler Moore Vision Initiative. The working group identified 12 variables of possible interest, 7 of which were judged to have sufficient preliminary data to suggest an association with DR to warrant further review: microperimetry, static automated perimetry, electroretinogram (ERG) oscillatory potentials, flicker ERG, low luminance visual acuity (LLVA), contrast sensitivity (CS), and BCVA. The objective field analyzer (OFA) was added after subsequent in-person workshops. Results: Currently, the only visual function test available for immediate use is BCVA; the remaining tests are either promising (within 5 years) or have potential (>5 years) use. Besides BCVA, most visual function tests had a limited role in current clinical care; however, LLVA, CS, flicker ERG, and OFA demonstrated potential for screening and research purposes. Conclusions: Although current visual function tests are promising, future prospective studies involving patients with early and more advanced retinopathy are necessary to determine if these tests can be used clinically or as endpoints for clinical studies. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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PURPOSE OF REVIEW: This article aims to illustrate the current state of investigations and management of liver metastases in patients with Neuroendocrine Neoplasms. Neuroendocrine tumours (NETs) are rising in incidence globally and have become the second most prevalent gastrointestinal malignancy in UK and USA. Frequently, patients have metastatic disease at time of presentation. The liver is the most common site of metastases for gastro-enteropancreatic NETs. Characterisation of liver metastases with imaging is important to ensure disease is not under-staged. RECENT FINDINGS: Magnetic resonance imaging and positron emission tomography are now becoming standard of care for imaging liver metastases. There is an increasing armamentarium of therapies available for management of NETs and loco-regional therapy for liver metastases. The data supporting surgical and loco-regional therapy is reviewed with focus on role of liver transplantation. It is important to use appropriate imaging and classification of NET liver metastases. It is key that decisions regarding approach to treatment is undertaken in a multidisciplinary team and that individualised approaches are considered for management of patients with metastatic NETs.
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Herpes simplex encephalitis (HSVE) is a potentially fatal infectious central nervous system (CNS) disorder. Thus, early detection is critical in determining the case's fate. Clinical history and examination, brain computed tomography, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and lumbar puncture have been used to establish a diagnosis. This report describes a case of HSVE with hypocellular cerebrospinal fluid (CSF) and an uncommon form of memory impairment. However, MRI results were consistent with HSVE, and CSF PCR tested positive for HSV-1 DNA that responded to treatment. We routinely advise patients to begin antiviral therapy as soon as possible to avoid complications.
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BACKGROUND: The role of a very low-calorie diet (VLCD) before cholecystectomy in obese patients is unclear. This study evaluated whether VLCD could be used as a risk mitigation strategy for this high-risk patient cohort. PATIENTS AND METHODS: A systematic review and meta-analysis was performed (PROSPERO ID CRD42022374610). The primary outcome was to determine the impact of pre-operative VLCD on the operative findings and ease of dissection during laparoscopic cholecystectomy (LC). RESULTS: Two studies were included with a total of 84 patients. VLCD was associated with a significantly easier Calot's dissection (MD: -0.58 (95% confidence interval [CI] [ -1.03, -0.13], P = 0.01) and was associated with a significantly higher rate of pre-operative weight loss (MD; 2.92 (95% CI [2.23, 3.62], P = 0.00001). CONCLUSIONS: The published evidence regarding VLCD before cholecystectomy in obese patients is limited. After acknowledging the limitations of the data, VLCD is associated with a significantly higher rate of weight loss preoperatively and directly impacts the ease of intraoperative dissection of Calot's triangle. Routine use of VLCD should be considered for all obese patients undergoing elective LC.
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BACKGROUND: Restless legs syndrome (RLS) emerges as a notable sleep disorder characterized by distressing sensations within the lower extremities. Its prevalence appears to be higher among patients afflicted with multiple sclerosis (MS) compared to the general population. Despite this observation, the understanding of the intricacies of RLS and its repercussions within the context of MS patients in Saudi Arabia remains limited. METHODS: Employing a cross-sectional design, a comprehensive investigation was undertaken at King Fahad Armed Forces Hospital in Jeddah, Saudi Arabia, spanning from November 2021 to March 2022. A cohort of 66 individuals diagnosed with MS was recruited and subjected to an assessment for RLS employing the revised diagnostic criteria outlined by the International Restless Legs Syndrome Study Group (IRLSSG). Furthermore, the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Sleepiness Scale were employed to gage the extent of RLS's impact on sleep quality and daily functioning. RESULTS: The prevalence of RLS amidst the MS cohort was determined to be 30.4%. An observable association was discerned between RLS presence and higher scores on the Expanded Disability Status Scale (p < 0.001), along with diminished sleep quality scores (p < 0.001) and elevated fatigue scores based on IRLSSG criteria (p < 0.001). Within the studied MS cases, 98.5 % exhibited the relapsing-remitting subtype. Further investigation demonstrated that patients treated with Fingolimod or Ocrevus presented normal IRLSSG scores, whereas those undergoing Rituximab treatment manifested an even distribution between normal and moderate scores. Correspondingly, patients receiving interferons showcased 72.2 % with normal scores and 27.8 % with mild scores. Notably, a statistically significant variance in IRLSSG scores was observed when contrasting Fingolimod and Aubagio treatments (P < 0.001). CONCLUSION: The presence of RLS as a comorbidity in MS patients within the Saudi Arabian context emerges as a significant finding, exerting a discernible detrimental influence on both disability status and sleep quality. This study underscores the need for further investigations aimed at unraveling the intricate pathophysiological underpinnings, identification of risk factors, and exploration of therapeutic modalities for RLS in this population. Furthermore, additional research endeavors are warranted to elucidate the diverse impact of various disease-modifying therapies on clinical outcomes.
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Esclerose Múltipla , Síndrome das Pernas Inquietas , Humanos , Arábia Saudita/epidemiologia , Projetos Piloto , Síndrome das Pernas Inquietas/tratamento farmacológico , Síndrome das Pernas Inquietas/epidemiologia , Prevalência , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Sonolência , Estudos Transversais , Cloridrato de Fingolimode , Índice de Gravidade de DoençaRESUMO
Introduction: Basic Life Support (BLS) is a medical treatment used in life-threatening emergencies until the sufferer can be properly cared for by a team of paramedics or in a hospital. This study aimed to assess the level of knowledge regarding BLS and the contributing factors among the Arab non-medical population. Methods: An online survey-based cross-sectional study was conducted among non-medical populations in nine Arab countries between April 13, 2022, and June 30, 2022. The utilized questionnaire consisted of two parts: part one included socio-demographic characteristics and part two measured knowledge of BLS through an online survey. Results: The research included a total of 4465 participants. 2540 (56.89%) of the participants were knowledgeable about BLS. The mean basic life support knowledge scores of participants who received training were higher than those who had not (20.11 ± 4.20 vs. 16.96 ± 5.27; p< 0.01). According to the nations, Yemen scored the highest, while Morocco had the lowest levels of BLS knowledge (19.86 ± 4.71 vs. 14.15 ± 5.10, respectively; p< 0.01). Additionally, individuals who resided in urban areas scored on average higher than those who did in rural areas (17.86 ± 5.19 vs. 17.13 ± 5.24, p= 0.032) in understanding basic life support. Age, information sources, and previous training with theoretical and practical classes were significant predictors of BLS knowledge. Conclusion: The level of BLS knowledge among non-medical people in Arab nations is moderate but insufficient to handle the urgent crises that we face everywhere. In addition to physicians being required to learn the BLS principles, non-medical people should also be knowledgeable of the necessary actions to take in emergency events.
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Endocardial-epicardial (Endo-epi) catheter ablation (CA) has been shown to reduce the rate of ventricular arrhythmia (VA) ablation in patients with structural heart disease (SHD). However, the effectiveness of this technique compared with endocardial (Endo) CA alone remains uncertain. This meta-analysis aims to compare the effectiveness of Endo-epi versus Endo alone in reducing the risk of VA recurrence in patients with SHD. We searched PubMed, Embase, and Cochrane Central Register with a comprehensive strategy. We used reconstructed time-to-event data to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for VA recurrence accompanied by at least one Kaplan-Meier curve for ventricular tachycardia recurrence. Our meta-analysis included 11 studies with a total of 977 patients. Endo-epi had a significantly lower risk of VA recurrence compared with those treated with Endo alone (HR 0.43, 95% CI 0.32 to 0.57, p <0.001). Subgroup analysis based on the type of cardiomyopathy revealed that patients with arrhythmogenic right ventricular cardiomyopathy and ischemic cardiomyopathy (ICM) benefited significantly from Endo-epi in reducing the risk of VA recurrence (HR 0.835, 0.55 to 0.87, p <0.021). However, there was no significant difference with non-ICM (HR 0.440, 0.55 to 0.87, p <0.33). The analysis of conditional survival showed that patients who remained free of VA recurrence for 5 years after the procedure had a very low probability of developing VA recurrence thereafter. In conclusion, Endo-epi CA is more effective than Endo CA alone in reducing the risk of VA recurrence in patients with SHD, especially those with arrhythmogenic right ventricular cardiomyopathy and ICM.
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Displasia Arritmogênica Ventricular Direita , Cardiomiopatias , Ablação por Cateter , Cardiopatias , Taquicardia Ventricular , Humanos , Displasia Arritmogênica Ventricular Direita/complicações , Displasia Arritmogênica Ventricular Direita/cirurgia , Resultado do Tratamento , Cardiopatias/complicações , Cardiopatias/cirurgia , Cardiomiopatias/etiologia , Ablação por Cateter/métodos , RecidivaRESUMO
COVID-19 vaccination has significantly reduced both the morbidity and mortality rates associated with SARS-CoV-2 infection. Vaccines, especially mRNA vaccines, have been proposed in several studies to complicate viral myocarditis. Thus, our systematic and meta-analysis review aims to further investigate the possibility of an association between COVID-19 vaccines and myocarditis. We systematically searched PubMed, Web of Science, Scopus, Ovid, and Google Scholar and did a gray search of other databases using the following keywords and terms: "Myocarditis ("Myocarditis" Mesh) OR "Chagas Cardiomyopathy" Mesh) AND "COVID-19 Vaccines" Mesh. The studies were limited to only English articles that reported myocardial inflammation or myocarditis associated with COVID-19 vaccines. Pooled risk ratio with its 95% confidence interval was analyzed by RevMan software (5.4) to perform the meta-analysis. Our study included 671 patients from 44 studies with a mean age of 14-40 years. Nevertheless, myocarditis was noted in a mean of (3.227) days, and 4.19 per million vaccination recipients experienced myocarditis. Most cases were clinically presented with manifestations of cough, chest pain, and fever. Laboratory tests revealed increased C-reactive protein, and troponin with all other cardiac markers in most patients. Cardiac magnetic resonance imaging (MRI) revealed late gadolinium enhancement with myocardial edema and cardiomegaly. Also, electrocardiograms revealed ST-segment elevation in most patients. Furthermore, the incidence of myocarditis was statistically significantly lower in the COVID-19 vaccine group as compared with the control group (RR = 0.15, 95% CI = 0.10-0.23, p-value < 0.00001). No significant association was found between COVID-19 vaccines and the incidence of myocarditis. The study's findings highlight the importance of implementing evidence-based COVID-19 prevention strategies, such as vaccination, to reduce the public health impact of COVID-19 and its associated complications.
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Background: Gaming addiction is a compulsive mental health condition that can have severe negative consequences on a person's life. As online gaming has increased during the COVID-19 pandemic, studies have shown a heightened risk of mental health issues. This study aims to assess the prevalence of severe phobia and addiction to online gaming among Arab adolescents and identify risk factors associated with these disorders. Methods: This cross-sectional study was conducted across 11 Arab nations. Participants were recruited using convenience sampling through an online survey distributed on social media platforms in 11 Arab countries. The survey included demographic questions, the Nine-item Internet Gaming Disorder Scale-Short Form (IGDS-SF9) to measure participants' online gaming addiction, the Social Phobia Scale (SPS), and questions assessing the impact of the COVID-19 pandemic on the prevalence of internet gaming addiction. The data were analyzed using SPSS win statistical package version 26. Results: Out of 2,458 participants, 2,237 were included in the sample due to non-response and missing data. The average age of the participants was 19.9 ± 4.8 years, and the majority were Egyptian and unmarried. 69% of the participants reported playing more than usual since the COVID-19 pandemic, as they were confined to their homes. Higher social phobia scores were associated with being single, male, and Egyptian. Participants from Egypt and those who felt that the pandemic significantly increased their gaming time had higher scores for online gaming addiction. Several major criteria, such as playing hours per day and beginning gaming at an early age, were associated with a higher level of online gaming addiction with social phobia. Conclusion: The study's findings suggest that there is a high prevalence of internet gaming addiction among Arab adolescents and young adults who play online games. The results also indicate a significant association between social phobia and several sociodemographic factors, which may inform future interventions and treatments for individuals with gaming addiction and social phobia.
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Infectious bursal disease (IBD) represents a greatly transmissible viral disease found worldwide, causing significant health and production challenges in young chickens. The aim of this research was to assess the immune reaction induced by different vaccines targeting IBD. These vaccines included recombinant (Vac1; HVT-IBD vector), immune complex (Vac2; Bursa-Plex®), and intermediate plus (Vac3; Bursine plus) IBD vaccines. Our assessment relied on serological and histopathological analyses, as well as the pattern of immune-related cytokine expression in the bursal tissue. The vaccinated groups, along with a control positive (CP) group, were subjected to a vvIBDV challenge on their 28th day of life, while the control negative (CN) group received a mock vaccination with PBS. Our study revealed that Vac1 resulted in the most favorable growth performance, as well as maintained normal liver and kidney function, mitigating the impact of IBDV infection. Serological analysis using VP2 ELISA kits indicated that Vac1 induced the strongest immunological response among all vaccines. Histopathological examination demonstrated that Vac1 caused minimal lymphoid depletion observed in the lymphoid organs, followed by Vac2. Analysis of cytokine expression profiles showed significant upregulation in all vaccinated groups, particularly Vac1, during the pre-challenge period. Following IBDV infection, Vac1 resulted in a noteworthy increase in the expression of IL2 and IFN-γ, Vac2 showed a significant upregulation in TNF-α and granzyme, and both Vac1 and Vac3 exhibited increased levels of IL1ß and IL10. In conclusion, our study suggests that the various vaccines triggered immune responses against IBD through both humoral and cell-mediated immunity. However, recombinant followed by immune complex vaccines appeared to induce more robust immunity while also being safer for broiler chickens in contrast to the intermediate plus vaccine.
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Exosomes, a class of extracellular vesicles of endocytic origin, play a critical role in paracrine signaling for successful cell-cell crosstalk in vivo. However, limitations in our current understanding of these circulating nanoparticles hinder efficient isolation, characterization, and downstream functional analysis of cell-specific exosomes. In this work, we sought to develop a method to isolate and characterize keratinocyte-originated exosomes (hExoκ) from human chronic wound fluid. Furthermore, we studied the significance of hExoκ in diabetic wounds. LC-MS-MS detection of KRT14 in hExoκ and subsequent validation by Vesiclepedia and Exocarta databases identified surface KRT14 as a reliable marker of hExoκ. dSTORM nanoimaging identified KRT14+ extracellular vesicles (EVκ) in human chronic wound fluid, 23% of which were of exosomal origin. An immunomagnetic two-step separation method using KRT14 and tetraspanin antibodies successfully isolated hExoκ from the heterogeneous pool of EV in chronic wound fluid of 15 non-diabetic and 22 diabetic patients. Isolated hExoκ (Ø75-150nm) were characterized per EV-track guidelines. dSTORM images, analyzed using online CODI followed by independent validation using Nanometrix, revealed hExoκ Ø as 80-145nm. The abundance of hExoκ was low in diabetic wound fluids and negatively correlated with patient HbA1c levels. The hExoκ isolated from diabetic wound fluid showed a low abundance of small bp RNA (<200 bp). Raman spectroscopy underscored differences in surface lipids between non-diabetic and diabetic hExoκ Uptake of hExoκ by monocyte-derived macrophages (MDM) was low for diabetics versus non-diabetics. Unlike hExoκ from non-diabetics, the addition of diabetic hExoκ to MDM polarized with LPS and INFγ resulted in sustained expression of iNOS and pro-inflammatory chemokines known to recruit macrophage (mÏ) This work provides maiden insight into the structure, composition, and function of hExoκ from chronic wound fluid thus providing a foundation for the study of exosomal malfunction under conditions of diabetic complications such as wound chronicity.
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Background: Clinically significant serrated polyp detection rate (CSSDR) and proximal serrated polyp detection rate (PSDR) have been suggested as the potential quality benchmarks for colonoscopy (CSSDR = 7% and PSDR = 11%) in comparison to the established benchmark adenoma detection rate (ADR). Another emerging milestone is the detection rate of lateral spreading lesions (LSLs). Objectives: This study aimed to evaluate CSSDR, PSDR, ADR, and LSL detection rates among gastrointestinal (GI) fellows performing a colonoscopy. A secondary aim was to evaluate patient factors associated with the detection rates of these lesions. Design and Methods: A retrospective review of 799 colonoscopy reports was performed. GI fellow details, demographic data, and pathology found on colonoscopy were collected. Multiple logistic regression analysis was performed to identify the factors associated with CSSDR, PSDR, ADR, and LSL detection rates. A p value < 0.05 was considered statistically significant. Results: For our patient population, the median age was 58 years; 396 (49.8%) were male and 386 (48.6%) were African American. The 15 GI fellows ranged from first (F1), second (F2), or third (F3) year of training. We found an overall CSSDR of 4.4%, PSDR of 10.5%, ADR of 42.1%, and LSL detection rate of 3.2%. Female gender was associated with CSSDR, while only age was associated with PSDR. GI fellow level of training was associated with LSL detection rate, with the odds of detecting them expected to be four times higher in F2/F3s than F1s. Conclusion: Although GI fellows demonstrated an above-recommended ADR and nearly reached target PSDR, they failed to achieve target CSSDR. Future studies investigating a benchmark for LSL detection rate are needed to quantify if GI fellows are detecting these lesions at adequate rates.
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The agricultural domain in developing countries is mostly dictated by archaic rules based on traditions and inherited practices. With the evolution of digitalization and technology, it seems essential to apply new technologies to the agricultural field. Among the technologies to be exploited in agriculture, we mention sensors, IoT, WSN, cloud, blockchain, etc. We talk about smart agriculture in this case. In this paper, we propose a platform secured by blockchain for monitoring and securing production. This platform uses IoT connected sensors to track and save data. Our system is used to monitor the production process of olive trees. The goal is to track everything that enters and leaves our olive tree production from fertilizers, insecticides, and fortifiers to olives, trimming etc. The blockchain via its decentralized system allow a secure, irreversible, and clear monitoring. A dashboard allow us to highlight the changes while facilitating the work of farmers. Our prototype will be embedded via a Raspberry Pi 4 platform.
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Blockchain , Inseticidas , Olea , FertilizantesRESUMO
Pembrolizumab is a monoclonal antibody which targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes. It is commonly used to treat many types of malignancies. Immunotherapy-related adverse events are relatively common and include pneumonitis, colitis and hepatitis. A rare side effect of immunotherapy is gastrointestinal (GI) bleeding secondary to hemorrhagic gastritis. Side effects from immunotherapy most commonly occur eight to twelve weeks after initiation of therapy but can vary from days after the first dose to even months later. We present a rare case of a patient with metastatic melanoma who had confirmed immune-mediated hemorrhagic gastritis which occurred after 23 cycles of Pembrolizumab. Biopsies for Heliobacter Pylori (H. pylori) and cytomegalovirus (CMV) were negative. The patient's immunotherapy was discontinued, and he was started on high dose steroids. The symptoms (nausea, vomiting, and abdominal pain) improved dramatically with a long steroid taper. An esophagogastroduodenoscopy (EGD) performed three months after hospital discharge showed improvement in gastric mucosa, but biopsies continued to show evidence of acute and chronic gastritis. As cancer patients continue to live longer with immunotherapy, it is important for all providers to be aware of the less common side effects of newer agents such as pembrolizumab.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Gastrite , Melanoma , Segunda Neoplasia Primária , Doença Aguda , Anticorpos Monoclonais/uso terapêutico , Gastrite/induzido quimicamente , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia/efeitos adversos , Masculino , Melanoma/tratamento farmacológico , Melanoma/patologia , Segunda Neoplasia Primária/etiologiaRESUMO
INTRODUCTION: Gastric electrical stimulation (GES) has been recommended for drug refractory patients with gastroparesis, but no clear baseline predictors of symptom response exist. We hypothesized that long-term predictors to GES for foregut and hindgut symptoms exist, particularly when using augmented energies. PATIENTS: We evaluated 307 patients at baseline, 1 week post temporary GES, and one year after permanent GES. Baseline measures included upper and lower symptoms by patient-reported outcomes (PRO), solid and liquid gastric emptying (GET), cutaneous, mucosal, and serosal electrophysiology (EGG, m/s EG), BMI, and response to temporary stimulation. METHODS: Foregut and hindgut PRO symptoms were analyzed for 12-month patient outcomes. All patients utilized a standardized energy algorithm with the majority of patients receiving medium energy at 12 months. Patients were categorized based on change in average GI symptom scores at the time of permanent GES compared to baseline using a 10% decrease over time as the cutoff between improvers versus non-improvers. RESULTS: By permanent GES implant, average foregut and hindgut GI symptom scores reduced 42% in improved patients (n = 199) and increased 27% in non-improved patients (n = 108). Low BMI, baseline infrequent urination score, mucosal EG ratio, and proximal mucosal EG low-resolution amplitude remained significant factors for improvement status. CONCLUSIONS: GES, for patients responding positively, improved both upper/foregut and lower/hindgut symptoms with most patients utilizing higher than nominal energies. Low baseline BMI and the presence of infrequent urination along with baseline gastric electrophysiology may help identify those patients with the best response to GES/bio-electric neuromodulation.
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Terapia por Estimulação Elétrica , Gastroparesia , Estimulação Elétrica , Esvaziamento Gástrico/fisiologia , Gastroparesia/terapia , Humanos , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates an array of cytoprotective genes, yet studies in transgenic mice have led to conflicting reports on its role in liver regeneration. We aimed to test the hypothesis that pharmacological activation of Nrf2 would enhance liver regeneration. APPROACH AND RESULTS: Wild-type and Nrf2 null mice were administered bardoxolone methyl (CDDO-Me), a potent activator of Nrf2 that has entered clinical development, and then subjected to two-thirds partial hepatectomy. Using translational noninvasive imaging techniques, CDDO-Me was shown to enhance the rate of restoration of liver volume (MRI) and improve liver function (multispectral optoacoustic imaging of indocyanine green clearance) in wild-type, but not Nrf2 null, mice following partial hepatectomy. Using immunofluorescence imaging and whole transcriptome analysis, these effects were found to be associated with an increase in hepatocyte hypertrophy and proliferation, the suppression of immune and inflammatory signals, and metabolic adaptation in the remnant liver tissue. Similar processes were modulated following exposure of primary human hepatocytes to CDDO-Me, highlighting the potential relevance of our findings to patients. CONCLUSIONS: Our results indicate that pharmacological activation of Nrf2 is a promising strategy for enhancing functional liver regeneration. Such an approach could therefore aid the recovery of patients undergoing liver surgery and support the treatment of acute and chronic liver disease.
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Regeneração Hepática/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/agonistas , Ácido Oleanólico/análogos & derivados , Adulto , Idoso de 80 Anos ou mais , Animais , Células Cultivadas , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatectomia , Hepatócitos , Humanos , Fígado/fisiologia , Fígado/cirurgia , Regeneração Hepática/genética , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Ácido Oleanólico/administração & dosagem , Cultura Primária de CélulasRESUMO
Enzyme-based assays have been extensively used for the early diagnosis of disease-related biomarkers. However, these assays are time-consuming, resource-intensive, and infrastructure-dependent, which renders them unsuitable and impractical for use in resource-constrained areas. Thus, there is a strong demand for a biocompatible and potentially generalizable sensor that can rapidly detect cancer biomarkers at ultralow concentration. Herein, an enzyme-free, cost-efficient, and easy-to-use assay based on a novel approach that entails fluorescent molecularly imprinting conjugated polythiophenes (FMICPs) for cancer biomarkers detection is developed. The promising conjugated polythiophenes structure, with a PLQY as high as 55%, provides a straightforward, and affordable method for free-enzyme signal generation. More importantly, the feasibility of integrating printed-paper technology with a sensitive and cost-effective smartphone and portable prototype testing device that could be utilized for rapid point-of-care (POC) cancer diagnostics is successfully introduced. Significantly, the unique structure of FMICP nanofibers (FMICP NFs) displays superior performance with enhanced sensitivity that is 80 times higher than that of pristine FMICP. This assay could lower the limits of detection to 15 fg mL-1 and 3.5 fg mL-1 for α-fetoprotein (AFP) and carcinoembryonic antigen (CEA), respectively, which are three orders of magnitude exceeding that of the standard enzyme-based assay. Moreover, the developed sensors are successfully applied to the fast diagnosis of AFP in liver cancer patients and the FMICP and FMICP NFs results are in excellent agreement with those of clinical ELISA.
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Antígeno Carcinoembrionário/análise , Polímeros Molecularmente Impressos/química , Nanofibras/química , Testes Imediatos , Polímeros/química , Tiofenos/química , alfa-Fetoproteínas/análise , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Antígeno Carcinoembrionário/sangue , Humanos , Limite de Detecção , Nanofibras/ultraestrutura , Neoplasias/sangue , Neoplasias/diagnóstico , Papel , Saliva/química , SmartphoneRESUMO
The efficient and selective delivery of therapeutic drugs to the target site remains the main obstacle in the development of new drugs and therapeutic interventions. Up until today, nanomicelles have shown their prospective as nanocarriers for drug delivery owing to their small size, good biocompatibility, and capacity to effectively entrap lipophilic drugs in their core. Nanomicelles are formed via self-assembly in aqueous media of amphiphilic molecules into well-organized supramolecular structures. Molecular weights and structure of the core and corona forming blocks are important properties that will determine the size of nanomicelles and their shape. Selective delivery is achieved via novel design of various stimuli-responsive nanomicelles that release drugs based on endogenous or exogenous stimulations such as pH, temperature, ultrasound, light, redox potential, and others. This review summarizes the emerging micellar nanocarriers developed with various designs, their outstanding properties, and underlying principles that grant targeted and continuous drug delivery. Finally, future perspectives, and challenges for nanomicelles are discussed based on the current achievements and remaining issues.