Subject(s)
Antibodies, Monoclonal, Humanized , Eosinophilic Esophagitis , Humans , Eosinophilic Esophagitis/drug therapy , Eosinophilic Esophagitis/diagnosis , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Child , Male , Female , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/diagnosisABSTRACT
OBJECTIVE: Metachromatic leukodystrophy (MLD) is a rare neurodegenerative disorder. Emerging therapies are most effective in the presymptomatic phase, and thus defining this window is critical. We hypothesize that early development delay may precede developmental plateau. With the advent of presymptomatic screening platforms and transformative therapies, it is essential to define the onset of neurologic disease. METHODS: The specific ages of gain and loss of developmental milestones were captured from the medical records of individuals affected by MLD. Milestone acquisition was characterized as: on target (obtained before the age limit of 90th percentile plus 2 standard deviations compared to a normative dataset), delayed (obtained after 90th percentile plus 2 standard deviations), or plateau (skills never gained). Regression was defined as the age at which skills were lost. LI-MLD was defined by age at onset before 2.5 years. RESULTS: Across an international cohort, 351 subjects were included (n = 194 LI-MLD subcohort). The median age at presentation of the LI-MLD cohort was 1.4 years (25th-75th %ile: 1.0-1.5). Within the LI-MLD cohort, 75/194 (39%) had developmental delay (or plateau) prior to MLD clinical presentation. Among the LI-MLD cohort with a minimum of 1.5 years of follow-up (n = 187), 73 (39.0%) subjects never attained independent ambulation. Within LI-MLD + delay subcohort, the median time between first missed milestone target to MLD decline was 0.60 years (maximum distance from delay to onset: 1.9 years). INTERPRETATION: Early developmental delay precedes regression in a subset of children affected by LI-MLD, defining the onset of neurologic dysfunction earlier than previously appreciated. The use of realworld data prior to diagnosis revealed an early deviation from typical development. Close monitoring for early developmental delay in presymptomatic individuals may help in earlier diagnosis with important consequences for treatment decisions.
Subject(s)
Age of Onset , Developmental Disabilities , Leukodystrophy, Metachromatic , Humans , Leukodystrophy, Metachromatic/diagnosis , Leukodystrophy, Metachromatic/pathology , Leukodystrophy, Metachromatic/genetics , Developmental Disabilities/diagnosis , Male , Female , Child, Preschool , Infant , Child , Adolescent , Cohort Studies , Disease ProgressionABSTRACT
In this study, essential oils and waste hydrosols of leaves of Ocimum tenuiflorum in four different geographical locations were extracted by hydrodistillation method and using gas chromatography / mass spectrometry (GC/MS) for chemical composition analysis. All four essential oil samples contained the main components (E)-ß-caryophyllene (27.8-49.0%), trans-ß-elemene (20.3-37.1%) and eugenol (9.0-44.0%). Three of the four hydrosol samples had eugenol in absolute content (94.5-98.6%), while the remaining hydrosol sample had two main components, elemicin (77.8%) and eugenol (14.2%). Essential oils and hydrosols demonstrated larvicidal activities against four important disease-transmitting mosquito species including Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Culex fuscocephala with 24-h LC50 values in the range 15.42-56.01 µg/mL and 53.88-97.80 µg/mL for the essential oils and the hydrosols, respectively. Essential oils and hydrosols strongly inhibited the acetylcholinesterase (AChE) enzyme of electric eels with IC50 values in the range of 25.35-107.19 µg/mL. Microemulsion (ME) can be considered as a sustainable pesticide formulation over 300 days and has improved larvicidal activity compared to free essential oil. The O. tenuiflorum in Vietnam can be considered a low-cost source of eugenol, botanical pesticides that control disease-transmitting mosquitoes, as well as having therapeutic potential to be further investigated.
ABSTRACT
Ultrasound (US) has gained popularity as a guidance modality for percutaneous needle insertions because it is widely available and non-ionizing. However, coordinating scanning and needle insertion still requires significant experience. Current assistance solutions utilize optical or electromagnetic tracking (EMT) technology directly integrated into the US device or probe. This results in specialized devices or introduces additional hardware, limiting the ergonomics of both the scanning and insertion process. We developed the first ultrasound (US) navigation solution designed to be used as a non-permanent accessory for existing US devices while maintaining the ergonomics during the scanning process. A miniaturized EMT source is reversibly attached to the US probe, temporarily creating a combined modality that provides real-time anatomical imaging and instrument tracking at the same time. Studies performed with 11 clinical operators show that the proposed navigation solution can guide needle insertions with a targeting accuracy of about 5 mm, which is comparable to existing approaches and unaffected by repeated attachment and detachment of the miniaturized tracking solution. The assistance proved particularly helpful for non-expert users and needle insertions performed outside of the US plane. The small size and reversible attachability of the proposed navigation solution promises streamlined integration into the clinical workflow and widespread access to US navigated punctures.
Subject(s)
Electromagnetic Phenomena , Needles , Humans , Ultrasonography, Interventional/methods , Ultrasonography, Interventional/instrumentation , Miniaturization , Equipment Design , Phantoms, ImagingSubject(s)
Genital Neoplasms, Female , Postoperative Complications , Pyrazoles , Pyridones , Humans , Female , Pyridones/therapeutic use , Pyridones/adverse effects , Pyridones/administration & dosage , Pyrazoles/therapeutic use , Pyrazoles/adverse effects , Genital Neoplasms, Female/surgery , Postoperative Complications/prevention & control , Prognosis , Thromboembolism/prevention & control , Thromboembolism/etiology , Factor Xa Inhibitors/therapeutic useABSTRACT
BACKGROUND: Stereotactic body radiation therapy (SBRT) is known to modulate the immune system and contribute to the generation of anti-tumor T cells and stimulate T cell infiltration into tumors. Radiation-induced immune suppression (RIIS) is a side effect of radiation therapy that can decrease immunological function by killing naive T cells as well as SBRT-induced newly created effector T cells, suppressing the immune response to tumors and increasing susceptibility to infections. PURPOSE: RIIS varies substantially among patients and it is currently unclear what drives this variability. Models that can accurately predict RIIS in near real time based on treatment plan characteristics would allow treatment planners to maintain current protocol specific dosimetric criteria while minimizing immune suppression. In this paper, we present an algorithm to predict RIIS based on a model of circulating blood using early stage lung cancer patients treated with SBRT. METHODS: This Python-based algorithm uses DICOM data for radiation therapy treatment plans, dose maps, patient CT data sets, and organ delineations to stochastically simulate blood flow and predict the doses absorbed by circulating lymphocytes. These absorbed doses are used to predict the fraction of lymphocytes killed by a given treatment plan. Finally, the time dependence of absolute lymphocyte count (ALC) following SBRT is modeled using longitudinal blood data up to a year after treatment. This model was developed and evaluated on a cohort of 64 patients with 10-fold cross validation. RESULTS: Our algorithm predicted post-treatment ALC with an average error of 0.24 ± 0.21 × 10 9 $0.24 \pm 0.21 \times {10}^9$ cells/L with 89% of the patients having a prediction error below 0.5 × 109 cells/L. The accuracy was consistent across a wide range of clinical and treatment variables. Our model is able to predict post-treatment ALC < 0.8 (grade 2 lymphopenia), with a sensitivity of 81% and a specificity of 98%. This model has a â¼38-s end-to-end prediction time of post treatment ALC. CONCLUSION: Our model performed well in predicting RIIS in patients treated using lung SBRT. With near-real time model prediction time, it has the capability to be interfaced with treatment planning systems to prospectively reduce immune cell toxicity while maintaining national SBRT conformity and plan quality criteria.
ABSTRACT
Excess soil salinity significantly impairs plant growth and development. Our previous reports demonstrated that the core circadian clock oscillator GIGANTEA (GI) negatively regulates salt stress tolerance by sequestering the SALT OVERLY SENSITIVE (SOS) 2 kinase, an essential component of the SOS pathway. Salt stress induces calcium-dependent cytoplasmic GI degradation, resulting in activation of the SOS pathway; however, the precise molecular mechanism governing GI degradation during salt stress remains enigmatic. Here, we demonstrate that salt-induced calcium signals promote the cytoplasmic partitioning of CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), leading to the 26S proteasome-dependent degradation of GI exclusively in the roots. Salt stress-induced calcium signals accelerate the cytoplasmic localization of COP1 in the root cells, which targets GI for 26S proteasomal degradation. Align with this, the interaction between COP1 and GI is only observed in the roots, not the shoots, under salt-stress conditions. Notably, the gi-201 cop1-4 double mutant shows an enhanced tolerance to salt stress similar to gi-201, indicating that GI is epistatic to COP1 under salt-stress conditions. Taken together, our study provides critical insights into the molecular mechanisms governing the COP1-mediated proteasomal degradation of GI for salt stress tolerance, raising new possibilities for developing salt-tolerant crops.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Plant Roots , Proteasome Endopeptidase Complex , Salt Tolerance , Ubiquitin-Protein Ligases , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Plant Roots/metabolism , Plant Roots/physiology , Plant Roots/genetics , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Salt Tolerance/genetics , Arabidopsis/genetics , Arabidopsis/physiology , Arabidopsis/metabolism , Proteasome Endopeptidase Complex/metabolism , Proteolysis/drug effects , Gene Expression Regulation, Plant , Mutation , Calcium/metabolismABSTRACT
BACKGROUND: Venous thromboembolism is a preventable complication of gynecologic cancer surgery that leads to postoperative morbidity and mortality. This study compared apixaban with enoxaparin to identify whether apixaban had the same safety and efficacy for patients undergoing gynecologic cancer surgery. METHODS: The study identified patients with a gynecologic malignancy who underwent surgery and were prescribed apixaban at discharge between June 2020 and April 2023. International Classification of Diseases 10 codes were used to identify patients who had a thromboembolism within 90 days or a bleeding event within 60 days after surgery. The rates of events for patients prescribed apixaban were compared with those for a historical cohort of patients who received enoxaparin. Fisher's exact tests were used to compare categorical variables, and t tests were used to compare continuous variables. A logistic regression was performed to compare the odds of thromboembolism between the two groups. RESULTS: Baseline patient characteristics differed in terms of body mass index (BMI), race, route of surgery, and type of cancer. Of the 490 patients in the apixaban cohort, 12 (2.4%) had a thromboembolism compared with 3 (2.1%) of the 138 patients in the enoxaparin group (adjusted odds ratio [aOR], 1.02; 95% confidence interval [CI] 0.30-4.70; p > 0.999). The odds ratio was adjusted for BMI, age, and route of surgery. A bleeding event occurred for 1 (0.2%) of the 490 patients in the apixaban group and for 1 (0.7%) of the 138 patients in the enoxaparin group. CONCLUSIONS: This validation study showed that apixaban is a safe and effective method of postoperative venous thromboembolism prophylaxis. The data provide support to previous data and guideline updates recommending the use of apixaban for postoperative prophylaxis.
Subject(s)
Enoxaparin , Genital Neoplasms, Female , Postoperative Complications , Pyrazoles , Pyridones , Humans , Female , Pyridones/therapeutic use , Pyridones/adverse effects , Pyridones/administration & dosage , Pyrazoles/therapeutic use , Pyrazoles/adverse effects , Middle Aged , Genital Neoplasms, Female/surgery , Postoperative Complications/prevention & control , Enoxaparin/therapeutic use , Enoxaparin/administration & dosage , Venous Thromboembolism/prevention & control , Venous Thromboembolism/etiology , Factor Xa Inhibitors/therapeutic use , Factor Xa Inhibitors/adverse effects , Follow-Up Studies , Aged , Prognosis , Gynecologic Surgical Procedures/adverse effects , Retrospective Studies , Anticoagulants/therapeutic use , Anticoagulants/administration & dosageABSTRACT
Importance: Despite interest in therapy de-escalation for survivors of human papillomavirus-mediated oropharyngeal squamous cell carcinoma (HPV-positive OPSCC), the association of de-escalated therapy with patient-reported quality of life (QoL) outcomes and burden of depressive symptoms remains unclear. Objective: To identify associations between clinicopathologic and therapeutic variables with patient-reported QoL outcomes and depression symptom burden in patients with HPV-positive OPSCC, who were enrolled in a therapy de-escalation trial. Design, Setting, and Participants: In this nonrandomized controlled, open-label, curative-intent therapy de-escalation clinical trial in adults with stage I, II, and III HPV-positive OPSCC, patients were recruited from a high-volume head and neck oncology practice. Main Outcomes and Measures: The main outcomes of this study included quantitative, patient-reported QoL and depression symptoms per well-validated inventories. Patient-reported QoL was based on Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) scores (range, 0-148; lower score indicates inferior QoL). Patient-reported depression-related symptom burden was based on Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) scores (range, 0-27; a higher score indicates a higher burden of depression symptoms). Baseline clinicopathologic and treatment variables were paired with FACT-HN and QIDS-SR scores at baseline, 3, 6, 12, 24, and 36 months. Linear mixed-effect models with a random intercept were used for each participant and fixed effects for other measures. Regression coefficients are reported with 95% CIs. Results: A total of 95 patients were followed up for a median (IQR) of 2.2 (1.6-3.2) years. Of these, 93 patients (98%) were male with a mean (SD) age of 60.5 (8.2) years. Overall, 54 participants (57%) had a history of current or former smoking, 47 (50%) underwent curative-intent surgery (with or without adjuvant therapy), and 48 (50%) underwent primary radiotherapy (with or without chemotherapy). The median (IQR) radiotherapy dose was 60 (60-70) Gy. Five deaths and 2 recurrence events were observed (mean [SD] recurrence interval, 1.4 [1.5] years). A higher radiotherapy dose was the only modifiable factor associated with inferior patient-reported QoL (lower FACT-HN) (coefficient, -0.66 [95% CI, -1.09 to -0.23]) and greater burden of depression-related symptoms (higher QIDS-SR) (coefficient, 0.11 [95% CI, 0.04-0.19]). With the 70-Gy dose as reference, improvements in FACT-HN and QIDS-SR scores were identified when patients received 51 to 60 Gy (coefficient, 12.75 [95% CI, 4.58-20.92] and -2.17 [-3.49 to -0.85], respectively) and 50 Gy or lower (coefficient, 15.03 [4.36-25.69] and -2.80 [-4.55 to -1.04]). Conclusions and Relevance: In this nonrandomized controlled, open-label, curative-intent therapy de-escalation trial, a higher radiotherapy dose was associated with inferior patient-reported QoL and a greater burden of depression-related symptoms. This suggests opportunities for improved QoL outcomes and reduced depression symptom burden with a reduction in radiotherapy dose. Trial Registration: ClinicalTrials.gov Identifier: NCT04638465.
Subject(s)
Depression , Oropharyngeal Neoplasms , Papillomavirus Infections , Quality of Life , Humans , Male , Oropharyngeal Neoplasms/therapy , Oropharyngeal Neoplasms/virology , Oropharyngeal Neoplasms/psychology , Oropharyngeal Neoplasms/pathology , Female , Middle Aged , Depression/etiology , Papillomavirus Infections/complications , Papillomavirus Infections/psychology , Aged , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/virology , Carcinoma, Squamous Cell/psychology , Carcinoma, Squamous Cell/pathology , Patient Reported Outcome Measures , Neoplasm StagingABSTRACT
Tomato (Solanum lycopersicum L.) is one of the most important crops in the world for its fruit production. Advances in cutting-edge techniques have enabled the development of numerous critical traits related to the quality and quantity of tomatoes. Genetic engineering techniques, such as gene transformation and gene editing, have emerged as powerful tools for generating new plant varieties with superior traits. In this study, we induced parthenocarpic traits in a population of elite tomato (ET) lines. At first, the adaptability of ET lines to genetic transformation was evaluated to identify the best-performing lines by transforming the SlANT1 gene overexpression cassette and then later used to produce the SlIAA9 knockout lines using the CRISPR/Cas9 system. ET5 and ET8 emerged as excellent materials for these techniques and showed higher efficiency. Typical phenotypes of knockout sliaa9 were clearly visible in G0 and G1 plants, in which simple leaves and parthenocarpic fruits were observed. The high efficiency of the CRISPR/Cas9 system in developing new tomato varieties with desired traits in a short period was demonstrated by generating T-DNA-free homozygous sliaa9 knockout plants in the G1 generation. Additionally, a simple artificial fertilization method was successfully applied to recover seed production from parthenocarpic plants, securing the use of these varieties as breeding materials. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01452-1.
ABSTRACT
OBJECTIVES: Burkholderia dolosa is a clinically important opportunistic pathogen in inpatients. Here we characterised an extensively drug-resistant and hypervirulent B. dolosa isolate from a patient hospitalised for stroke. METHODS: Resistance to 41 antibiotics was tested with the agar disc diffusion, minimum inhibitory concentration, or broth microdilution method. The complete genome was assembled using short-reads and long-reads and the hybrid de novo assembly method. Allelic profiles obtained by multilocus sequence typing were analysed using the PubMLST database. Antibiotic-resistance and virulence genes were predicted in silico using public databases and the 'baargin' workflow. B. dolosa N149 phylogenetic relationships with all available B. dolosa strains and Burkholderia cepacia complex strains were analysed using the pangenome obtained with Roary. RESULTS: B. dolosa N149 displayed extensive resistance to 31 antibiotics and intermediate resistance to 4 antibiotics. The complete genome included three circular chromosomes (6 338 630 bp in total) and one plasmid (167 591 bp). Genotypic analysis revealed various gene clusters (acr, amr, amp, emr, ade, bla and tet) associated with resistance to 35 antibiotic classes. The major intrinsic resistance mechanisms were multidrug efflux pump alterations, inactivation and reduced permeability of targeted antibiotics. Moreover, 91 virulence genes (encoding proteins involved in adherence, formation of capsule, biofilm and colony, motility, phagocytosis inhibition, secretion systems, protease secretion, transmission and quorum sensing) were identified. B. dolosa N149 was assigned to a novel sequence type (ST2237) and formed a mono-phylogenetic clade separated from other B. dolosa strains. CONCLUSIONS: This study provided insights into the antimicrobial resistance and virulence mechanisms of B. dolosa.
Subject(s)
Anti-Bacterial Agents , Burkholderia Infections , Drug Resistance, Multiple, Bacterial , Genome, Bacterial , Microbial Sensitivity Tests , Multilocus Sequence Typing , Phylogeny , Stroke , Humans , Anti-Bacterial Agents/pharmacology , Vietnam , Burkholderia Infections/microbiology , Stroke/microbiology , Burkholderia/genetics , Burkholderia/drug effects , Burkholderia/isolation & purification , Burkholderia/classification , Burkholderia/pathogenicity , Virulence/genetics , Virulence Factors/genetics , Whole Genome Sequencing , Southeast Asian PeopleABSTRACT
OBJECTIVE: To determine biomarkers other than CA 125 that could be used in identifying early-stage ovarian cancer. DATA SOURCES: Ovid MEDLINE ALL, EMBASE, Web of Science Core Collection, ScienceDirect, Clinicaltrials.gov , and CAB Direct were searched for English-language studies between January 2008 and April 2023 for the concepts of high-grade serous ovarian cancer, testing, and prevention or early diagnosis. METHODS OF STUDY SELECTION: The 5,523 related articles were uploaded to Covidence. Screening by two independent reviewers of the article abstracts led to the identification of 245 peer-reviewed primary research articles for full-text review. Full-text review by those reviewers led to the identification of 131 peer-reviewed primary research articles used for this review. TABULATION, INTEGRATION, AND RESULTS: Of 131 studies, only 55 reported sensitivity, specificity, or area under the curve (AUC), with 36 of the studies reporting at least one biomarker with a specificity of 80% or greater specificity or 0.9 or greater AUC. CONCLUSION: These findings suggest that although many types of biomarkers are being tested in ovarian cancer, most have similar or worse detection rates compared with CA 125 and have the same limitations of poor detection rates in early-stage disease. However, 27.5% of articles (36/131) reported biomarkers with better sensitivity and an AUC greater than 0.9 compared with CA 125 alone and deserve further exploration.
Subject(s)
Fallopian Tubes , Ovarian Neoplasms , Female , Humans , Ovarian Neoplasms/diagnosis , BiomarkersABSTRACT
BACKGROUND: Radiotherapy is an essential component of cancer treatment, yet many countries do not have adequate capacity to serve all patients who would benefit from it. Allocation systems are needed to guide patient prioritization for radiotherapy in resource-limited contexts. These systems should be informed by allocation principles deemed relevant to stakeholders. This study explores the ethical dilemmas and views of decision-makers engaged in real-world prioritization of scarce radiotherapy resources at a cancer center in Rwanda in order to identify relevant principles. METHODS: Semi-structured interviews were conducted with a purposive sample of 22 oncology clinicians, program leaders, and clinical advisors. Interviews explored the factors considered by decision-makers when prioritizing patients for radiotherapy. The framework method of thematic analysis was used to characterize these factors. Bioethical analysis was then applied to determine their underlying normative principles. RESULTS: Participants considered both clinical and non-clinical factors relevant to patient prioritization for radiotherapy. They widely agreed that disease curability should be the primary overarching driver of prioritization, with the goal of saving the most lives. However, they described tension between curability and competing factors including age, palliative benefit, and waiting time. They were divided about the role that non-clinical factors such as social value should play, and agreed that poverty should not be a barrier. CONCLUSIONS: Multiple competing principles create tension with the agreed upon overarching goal of maximizing lives saved, including another utilitarian approach of maximizing life-years saved as well as non-utilitarian principles, such as egalitarianism, prioritarianism, and deontology. Clinical guidelines for patient prioritization for radiotherapy can combine multiple principles into a single allocation system to a significant extent. However, conflicting views about the role that social factors should play, and the dynamic nature of resource availability, highlight the need for ongoing work to evaluate and refine priority setting systems based on stakeholder views.
ABSTRACT
One new indol, N-methoxymethyltryptophol (1), one new phenolic, (2 R)-2-(4-hydroxyphenyl)ethyl 2-hydroxy-3-phenylpropanoate (2) and fifteen known compounds (3-17) were isolated from the methanol extract of the fermentation of marine microalgae Aurantiochytrium sp. SC145. Their structures were elucidated by 1D-, 2D-NMR spectroscopic analysis, HR-ESI-MS, quantum chemical calculation methods and by comparing their NMR data with those reported in the literature. All compounds were evaluated for their antimicrobial activities against microorganisms. Compounds 2, 3 and 11 significantly exhibited antimicrobial activities on all tested Gram-(+), Gram-(-) bacteria and the yeast C. albicans with MIC values ranging from 32 to 256 µg/mL.
Subject(s)
Anti-Infective Agents , Microalgae , Anti-Infective Agents/chemistry , Bacteria , Plant Extracts/chemistry , Yeasts , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistryABSTRACT
OBJECTIVES: Complement factor I (CFI) deficiency is a rare autosomal recessive inborn error of immunity. In this report, we highlight that complete CFI deficiency may present with isolated and severe CNS inflammation without associated systemic features nor prior non-CNS episodes. This inflammation may respond to complement blockade therapy. METHODS: This is a case description of a young girl with severe longitudinal transverse myelitis treated with aggressive immunotherapy that included eculizumab. Published cases of CFI-associated CNS inflammation were reviewed and discussed. RESULTS: A primary immunodeficiency panel revealed 2 germline pathogenic variants in the CFI gene. Further complement testing of the index case and her family confirmed complete CFI deficiency. DISCUSSION: We describe a unique case of severe spinal inflammation secondary to complete CFI deficiency. Although rare, isolated CNS inflammation may be the primary manifestation of complete CFI deficiency. To halt the uncontrolled complement-mediated inflammation associated with CFI deficiency, prompt targeted blockade of the complement pathway using eculizumab may be life changing in the acute phase. Long-lasting blockade of the complement pathway is also essential to prevent relapse in this subgroup of patients.
Subject(s)
Complement C3 , Neoplasm Recurrence, Local , Humans , Female , Hereditary Complement Deficiency Diseases , InflammationABSTRACT
BACKGROUND: The quantitative outcome of secondary reanimation after a failed primary reconstruction attempt for facial paralysis is rarely reported in the literature. This study aimed to investigate the feasibility of secondary reanimation with gracilis free muscle transfer (GFMT) and whether this outcome is influenced by the primary reconstruction. METHODS: Twelve patients with previously failed static procedures (static group, n = 6), temporal muscle transfer (temporal transfer group, n = 2), and GFMT (GFMT group, n = 4) were all secondarily reanimated with GFMT. The clinical outcome was graded with the eFACE metric. The objective oral commissure excursion was measured with Emotrics, and the artificial intelligence software FaceReader evaluated the intensity score (IS) of emotional expression. RESULTS: The mean follow-up was 40 ± 27 months. The eFACE metric showed a statistically significant (p < 0.05) postoperative improvement in the dynamic and smile scores across all groups. In the GFMT group, oral commissure with smile (75.75 ± 20.43 points), oral commissure excursion while smiling with teeth showing (32.7 ± 4.35 mm), and the intensity of happiness emotion while smiling without teeth showing (IS of 0.37 ± 0.23) were significantly lower as compared with the static group postoperatively (98.83 ± 2.86 points, p = 0.038; 41.7 ± 4.35 mm, p = 0.025; IS 0.83 ± 0.16, p = 0.01). CONCLUSIONS: Our data suggest that secondary dynamic reconstruction with GFMT is feasible should the primary reconstruction fail. The secondary GFMT appears to improve the outcome of primary GFMT; however, the oral commissure excursion while smiling might be lower than that in patients who had static procedures as primary reconstruction.
Subject(s)
Facial Paralysis , Gracilis Muscle , Nerve Transfer , Plastic Surgery Procedures , Humans , Artificial Intelligence , Treatment Outcome , Gracilis Muscle/transplantation , Smiling/physiology , Facial Paralysis/surgery , Facial Paralysis/psychology , Nerve Transfer/methods , Retrospective StudiesABSTRACT
Fucoxanthin extracted and purified from Vietnamese Sargassum oligocystum Montagne, 1845 exhibits various biological activities. In this study, the ability of fucoxanthin to inhibit acetylcholinesterase (AChE), the antioxidant activities, and the expression of antioxidant enzymes were investigated. Fucoxanthin isolated from Vietnamese S. oligocystum showed no cytotoxic effects; moreover, it exhibited AChE inhibitory activity (with an IC50 value of 130.12 ± 6.65 µg mL-1) and antioxidant activity (with an IC50 value of 3.42 ± 0.15 mg mL-1). At concentrations of 50 and 100 µg mL-1, fucoxanthin provided protection against amyloid ß-protein fragment 25-35-induced neurotoxicity in a C6 neuronal cell line, and the survival of C6 cells was higher than 81.01% and 80.98%, respectively, compared to the control group (59%). Moreover, antioxidant enzyme activity and quantitative PCR analysis suggested that the neuroprotective effect of fucoxanthin resulted from regulation of the gene expression of antioxidant enzymes (CAT and GPx) and ER pathways (caspase-3 and Bax), as well as the promotion of expression of genes involved in PI3K/Akt signaling (GSK-3ß), autophagy (p62 and ATG5), and the biosynthesis of ACh (VAChT and ChAT). Therefore, fucoxanthin extracted from the seaweed S. oligocystum in Vietnam is a potential feedstock source for the production of health foods that exert neuroprotective effects.
ABSTRACT
A novel cyanine compound based on the conjugated perylene-benzothiazole system (PBI) as a colorimetric and fluorometric dual-channel sensor for cyanide (CN- ) detection was synthesized and characterized via UV-vis and fluorescence spectroscopy. PBI exhibited a high sensitivity and rapid optical response for CN- due to the intramolecular charge transfer (ICT) mechanism. The detection limit of PBI for CN- was 1.15×10-7 â M in the mixture of DMSO/H2 O (1 : 1, v/v). Moreover, probe PBI demonstrated high selectivity and sensitivity for CN- over other common anions, including Cl- , Br- , F- , I- , AcO- , ClO4 - , HSO4 - , SO4 2- , NO2 - , NO3 - and SCN- . This work provided a simple and effective approach to trace the toxic CN- ion with rapid response, high selectivity, and sensitivity that is possibly applied in environmental control and agricultural management.
ABSTRACT
Crackling noise is a scale-invariant phenomenon found in various driven nonlinear dynamical material systems as a response to external stimuli such as force or external fields. Jerky material movements in the form of avalanches can span many orders of magnitude in size and follow universal scaling rules described by power laws. The concept was originally studied as Barkhausen noise in magnetic materials and now is used in diverse fields from earthquake research and building materials monitoring to fundamental research involving phase transitions and neural networks. Here, we demonstrate a method for nanoscale crackling noise measurements based on AFM nanoindentation, where the AFM probe can be used to study the crackling of individual nanoscale features, a technique we call crackling noise microscopy. The method is successfully applied to investigate the crackling of individual topological defects, i.e. ferroelectric domain walls. We show that critical exponents for avalanches are altered at these nanoscale features, leading to a suppression of mixed-criticality, which is otherwise present in domains. The presented concept opens the possibility of investigating the crackling of individual nanoscale features in a wide range of material systems.
ABSTRACT
BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described neuroinflammatory demyelinating disease. OBJECTIVE: To better understand the clinical spectrum, risk factors and outcomes in MOGAD. METHODS: Retrospective cohort study including all subjects harboring anti-MOG antibodies identified in major academic hospitals across the province of Quebec. RESULTS: We identified 45 MOGAD cases. The minimal estimated point-prevalence was 0.52/100 000 in Quebec. Median age at presentation was 32 years (range 1-71) with equal sex ratio. Most frequent ethnic groups were Caucasians and Asians. The most frequent clinical manifestations at onset were optic neuritis (ON), affecting 56% of adults, and acute disseminated encephalomyelitis (ADEM), affecting 33% of children. First MRI was abnormal in 84% of cases. Most CSF samples showed pleocytosis without oligoclonal bands. Two brain biopsies revealed lipid-laden macrophages and reactive astrocytes. Despite steroids, only 38% had fully recovered at 4 weeks after onset. Half of pediatric and two thirds of adult-onset MOGAD subjects experienced relapses. At last follow-up, 69% showed residual deficits, which were moderate to severe in 17% of adults. CONCLUSION: MOGAD has heterogeneous disease course, and it is not a benign disease for a substantial proportion of adults. Best disease-modifying therapies remain to be determined.