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1.
ACS Omega ; 9(27): 29651-29665, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39005831

RESUMO

Novel research on the chemical compositions and biochemical activities of Camellia longii Orel and Luu leaf extracts revealed valuable resources with potential applications in Alzheimer's disease treatment. Qualitative phytochemicals detected various compound groups, including polyphenols, saponins, tannins, flavonoids, alkaloids, amino acids, coumarins, and polysaccharides. HPLC-MS identified 23 compounds in C. longii leaves with compounds found at significant levels, including epicatechin gallate (17.12%), tryptophan (13.73%), isovitexin (12.91%), gallic acid (3.06%), and quercetin (3.06%). Interestingly, the ethanol extract (CLL-Ew) exhibited the highest extraction yield (26.6%) and potent antioxidant and acetylcholinesterase (AChE) inhibitory effects in vitro. In the Drosophila melanogaster model, CLL-Ew improved longevity, movement, and memory by reducing malondialdehyde and increasing glutathione levels. Docking simulations suggested that the above compounds bind tightly to AChE's active site, potentially contributing to memory enhancement. Interestingly, observations of male and female mice after administration of a dose of 5000 mg/kg C. longii leaf extract were recorded normally throughout the 14 day experiment. These findings highlight the potential of C. longii leaf extracts in functional foods and therapeutic interventions for memory impairment prevention and treatment.

2.
Cureus ; 16(6): e62967, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39044895

RESUMO

Objective This study aims to identify factors associated with mosaicism in human embryos at Hung Vuong Hospital. Methods We performed a retrospective analysis of data from 2018 to 2022, approved by the Hung Vuong Hospital Ethics Committee (CS/HV/23/15). We analyzed variables such as demographic characteristics, clinical measurements, and in-vitro fertilization (IVF) cycle outcomes to investigate their relationship with embryo mosaicism. Results A total of 73 couples undergoing IVF with preimplantation genetic testing (PGT) were included in the analysis. Among 308 embryos, 98 (31.8%) were mosaic, 124 (40.3%) were euploid, and 86 (27.9%) were aneuploid. Univariable analysis revealed that female age was significantly associated with increased odds of mosaicism (odd ratio (OR) = 1.11, 95% confidence interval (CI): 1.04 - 1.19, p = 0.003). Male age demonstrated a marginal association with mosaicism (OR = 1.05, 95% CI: 1.00 - 1.11, p = 0.07). Other factors, including body mass index (BMI), anti-Mullerian hormone (AMH) levels, blood types, and sperm quality, were not significantly associated with mosaicism. In the multivariable analysis, controlling for both female and male age, female age showed a trend toward significance (OR = 1.12, 95% CI: 1.02 - 1.23, p = 0.02), while male age showed no significant effect (OR = 0.99, 95% CI: 0.92 - 1.06, p = 0.75). Conclusions The findings suggest that female age is a critical factor influencing the occurrence of mosaicism in embryos. Further research is needed to fully understand the mechanisms underlying mosaicism in human embryos.

3.
Children (Basel) ; 11(7)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-39062213

RESUMO

Arachnoid granulations (AGs) are generally benign structures within the subarachnoid space that extend into the dural sinuses and calvarial bone. They can present in a variety of sizes but are termed 'giant' arachnoid granulations (GAGs) when they are larger than 1 cm in diameter or take up a significant portion of the dural sinus' lumen. Vermiform giant arachnoid granulations are a specific type of GAG that are known for their worm-like appearance. Specifically, these vermiform GAGs can be challenging to diagnose as they can mimic other pathologies like dural sinus thrombosis, sinus cavernomas, or brain tumors. In this case series, we present two cases of vermiform giant arachnoid granulations, discuss their imaging characteristics and highlight the diagnostic challenges to improve identification and prevent misdiagnoses.

4.
Ann Vasc Surg ; 109: 316-325, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39067852

RESUMO

BACKGROUND: Abdominal aortic aneurysm (AAA) is a complex disease with environmental and genetic risk factors. Polygenic risk scores (PRSs) based on disease-specific risk-associated single nucleotide variants (SNVs) have demonstrated effectiveness in stratifying individual-level disease risk for cardiovascular diseases. This prospective cohort study assessed associations of PRS of AAA (PRSAAA) with risk of incident AAA, analyzed the effectiveness of a combined clinical-genetic risk model, and explored the clinical utility of the model in identifying high-risk individuals for AAA screening. METHODS: PRSAAA was calculated using 911,440 SNVs and PRS of coronary artery disease was calculated using 2,324,683 SNVs derived from mixed ancestry genome-wide association studies. The UK Biobank was used as the study cohort. All individuals with complete genetic data available and no diagnosis of AAA at the time of recruitment were included in the analysis and followed prospectively to assess for incident AAA. A PRS-informed clinical model, Prob-AAA, was developed using clinically significant variables and PRSAAA. RESULTS: Four hundred eighty-one thousand one hundred 5 individuals were included in the analysis with 2,668 incident AAA cases. Incident AAA increased from 0.30 to 0.93% between the lowest and highest decile of PRSAAA; similarly, severe AAA, requiring surgery and/or presenting with rupture, increased from 23 to 39% of incident AAA cases across deciles. PRSAAA was a predictor of incident AAA diagnosis (hazard ratio 2.06 [1.70-2.48]) independent of other clinical risk factors including male sex, older age, and smoking history. Prob-AAA was an independent predictor of incident AAA (hazard ratio 1.92 [1.69-2.20]), and identified 9.6% of cases of incident AAA compared to only 4.2% by PRSAAA. Current screening guidelines captured 5.7% of the overall cohort, with an incident AAA rate of approximately 3.2%. Among males not included by current guidelines, Prob-AAA identified an additional cohort, approximately 2% of the overall cohort, with a similar rate of incident AAA. CONCLUSIONS: Prob-AAA, a PRS-informed clinical model for AAA, improved upon the predictive power of current, clinical risk factor-informed, screening guidelines for AAA.

5.
Int J Infect Dis ; 146: 107133, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38876162

RESUMO

OBJECTIVES: To determine the associated pathogen during the 2023 conjunctivitis outbreak in Vietnam METHODS: RNA-sequencing was used to identify pathogens before and during the outbreak. RESULTS: 24 patients with infectious conjunctivitis between March and October 2023 from Hai Yen Vision Institute in Vietnam were swabbed. Coxsackievirus A24v was the most common pathogen identified. Phylogenetic analysis of these strains demonstrates similarities to the Coxsackievirus identified in the 2022 India outbreak. Human adenovirus D was also circulating. Ocular findings of tearing, purulence, and itching were common in this outbreak. CONCLUSIONS: Multiple viruses can co-circulate during conjunctivitis outbreaks. Hemorrhagic conjunctivitis, commonly associated with coxsackievirus conjunctivitis, was not a common clinical sign in this outbreak. Repeat genetic surveillance, with the notable inclusion of RNA virus detection strategies, is important for outbreak detection.


Assuntos
Infecções por Coxsackievirus , Surtos de Doenças , Filogenia , Humanos , Vietnã/epidemiologia , Infecções por Coxsackievirus/epidemiologia , Infecções por Coxsackievirus/virologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Criança , Adolescente , Pré-Escolar , Conjuntivite Viral/epidemiologia , Conjuntivite Viral/virologia , Conjuntivite Hemorrágica Aguda/epidemiologia , Conjuntivite Hemorrágica Aguda/virologia
6.
Int J Cardiol ; 404: 131990, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38521508

RESUMO

BACKGROUND: Current risk assessment for ischemic stroke (IS) is limited to clinical variables. We hypothesize that polygenic scores (PGS) of IS (PGSIS) and IS-associated diseases such as atrial fibrillation (AF), venous thromboembolism (VTE), coronary artery disease (CAD), hypertension (HTN), and Type 2 diabetes (T2D) may improve the performance of IS risk assessment. METHODS: Incident IS was followed for 479,476 participants in the UK Biobank who did not have an IS diagnosis prior to the recruitment. Lifestyle variables (obesity, smoking and alcohol) at the time of study recruitment, clinical diagnoses of IS-associated diseases, PGSIS, and five PGSs for IS-associated diseases were tested using the Cox proportional-hazards model. Predictive performance was assessed using the C-statistic and net reclassification index (NRI). RESULTS: During a median average 12.5-year follow-up, 8374 subjects were diagnosed with IS. Known clinical variables (age, gender, clinical diagnoses of IS-associated diseases, obesity, and smoking) and PGSIS were all independently associated with IS (P < 0.001). In addition, PGSIS and each PGS for IS-associated diseases was also independently associated with IS (P < 0.001). Compared to the clinical model, a joint clinical/PGS model improved the C-statistic for predicting IS from 0.71 to 0.73 (P < 0.001) and significantly reclassified IS risk (NRI = 0.017, P < 0.001), and 6.48% of subjects were upgraded from low to high risk. CONCLUSIONS: Adding PGSs of IS and IS-associated diseases to known clinical risk factors statistically improved risk assessment for IS, demonstrating the supplementary value of inherited susceptibility measurement . However, its clinical utility is likely limited due to modest improvements in predictive values.


Assuntos
Fibrilação Atrial , Diabetes Mellitus Tipo 2 , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética , Diabetes Mellitus Tipo 2/complicações , Fatores de Risco , Medição de Risco , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/genética , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/genética
7.
Geohealth ; 8(3): e2023GH000938, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38449816

RESUMO

Emissions from flaring and venting (FV) in oil and gas (O&G) production are difficult to quantify due to their intermittent activities and lack of adequate monitoring and reporting. Given their potentially significant contribution to total emissions from the O&G sector in the United States, we estimate emissions from FV using Visible Infrared Imaging Radiometer Suite satellite observations and state/local reported data on flared gas volume. These refined estimates are higher than those reported in the National Emission Inventory: by up to 15 times for fine particulate matter (PM2.5), two times for sulfur dioxides, and 22% higher for nitrogen oxides (NOx). Annual average contributions of FV to ozone (O3), NO2, and PM2.5 in the conterminous U.S. (CONUS) are less than 0.15%, but significant contributions of up to 60% are found in O&G fields with FV. FV contributions are higher in winter than in summer months for O3 and PM2.5; an inverse behavior is found for NO2. Nitrate aerosol contributions to PM2.5 are highest in the Denver basin whereas in the Permian and Bakken basins, sulfate and elemental carbon aerosols are the major contributors. Over four simulated months in 2016 for the entire CONUS, FV contributes 210 additional instances of exceedances to the daily maximum 8-hr average O3 and has negligible contributions to exceedance of NO2 and PM2.5, given the current form of the national ambient air quality standards. FV emissions are found to cause over $7.4 billion in health damages, 710 premature deaths, and 73,000 asthma exacerbations among children annually.

8.
Am J Case Rep ; 25: e943166, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38425030

RESUMO

BACKGROUND Pneumatosis intestinalis (PI) is an uncommon condition that is not specific to any particular disease. Currently, there is no specific clinical guideline for treating and diagnosing PI. Furthermore, there are numerous causes of PI, which makes it difficult for clinicians - internal medicine physicians as well as surgeons - to take a clinical approach to diagnosis and treatment. CASE REPORT We present 3 clinical scenarios with PI. In the first patient there was a solitary image of PI, which was treated successfully with parenteral nutrition and intravenous antibiotics, and he was discharged after 5 days. The other 2 cases, which involve gas in the hepatic portal vein (HPVG), were handled in 2 distinct ways: surgically and conservatively. One needed diagnostic laparoscopy with necrotic segmentectomy and was discharged from the hospital on postoperative day 16. The last patient, received resuscitation treatment due to severe comorbidities and inability to tolerate surgery. After 3 days, abdominal CT scan revealed no signs of remaining PI. However, the patient was terminally discharged after 7 weeks of treatment due to septic shock caused by sacrococcygeal ulcer and urinary tract infection. By drawing comparisons among these 3 scenarios, we aim to highlight certain indicators for conservative treatment success. CONCLUSIONS PI with HPVG is a sign of severe prognosis, which often requires surgical intervention. However, the decision to manage conservatively or surgically depends on the patient's condition and other criteria such as peritonitis, free fluid in the abdominal cavity, and the presence of shock. Physicians should also weigh the benefits and risks of surgical intervention in critically ill patients.


Assuntos
Cavidade Abdominal , Laparoscopia , Masculino , Humanos , Veia Porta , Necrose , Tomografia Computadorizada por Raios X/métodos
9.
PLoS Negl Trop Dis ; 18(3): e0012071, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38536887

RESUMO

Dengue shock (DS) is the most severe complication of dengue infection; endothelial hyperpermeability leads to profound plasma leakage, hypovolaemia and extravascular fluid accumulation. At present, the only treatment is supportive with intravenous fluid, but targeted endothelial stabilising therapies and host immune modulators are needed. With the aim of prioritising potential therapeutics, we conducted a prospective observational study of adults (≥16 years) with DS in Vietnam from 2019-2022, comparing the pathophysiology underlying circulatory failure with patients with septic shock (SS), and investigating the association of biomarkers with clinical severity (SOFA score, ICU admission, mortality) and pulmonary vascular leak (daily lung ultrasound for interstitial and pleural fluid). Plasma was collected at enrolment, 48 hours later and hospital discharge. We measured biomarkers of inflammation (IL-6, ferritin), endothelial activation (Ang-1, Ang-2, sTie-2, VCAM-1) and endothelial glycocalyx breakdown (hyaluronan, heparan sulfate, endocan, syndecan-1). We enrolled 135 patients with DS (median age 26, median SOFA score 7, 34 required ICU admission, 5 deaths), together with 37 patients with SS and 25 healthy controls. Within the DS group, IL-6 and ferritin were associated with admission SOFA score (IL-6: ßeta0.70, p<0.001 & ferritin: ßeta0.45, p<0.001), ICU admission (IL-6: OR 2.6, p<0.001 & ferritin: OR 1.55, p<0.001) and mortality (IL-6: OR 4.49, p = 0.005 & ferritin: OR 13.8, p = 0.02); both biomarkers discriminated survivors and non-survivors at 48 hours and all patients who died from DS had pre-mortem ferritin ≥100,000ng/ml. IL-6 most strongly correlated with severity of pulmonary vascular leakage (R = 0.41, p<0.001). Ang-2 correlated with pulmonary vascular leak (R = 0.33, p<0.001) and associated with SOFA score (ß 0.81, p<0.001) and mortality (OR 8.06, p = 0.002). Ang-1 was associated with ICU admission (OR 1.6, p = 0.005) and mortality (OR 3.62, p = 0.006). All 4 glycocalyx biomarkers were positively associated with SOFA score, but only syndecan-1 was associated with ICU admission (OR 2.02, p<0.001) and mortality (OR 6.51, p<0.001). This study highlights the central role of hyperinflammation in determining outcomes from DS; the data suggest that anti-IL-1 and anti-IL-6 immune modulators and Tie2 agonists may be considered as candidates for therapeutic trials in severe dengue.


Assuntos
Sepse , Dengue Grave , Choque Séptico , Adulto , Humanos , Sindecana-1 , Estudos Prospectivos , Vietnã/epidemiologia , Interleucina-6 , Biomarcadores , Ferritinas , Prognóstico , Unidades de Terapia Intensiva , Sepse/complicações
10.
Acad Radiol ; 31(2): 660-683, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37120403

RESUMO

RATIONALE AND OBJECTIVES: Recent advancements in artificial intelligence (AI) render a substantial promise for epidermal growth factor receptor (EGFR) mutation status prediction in non-small cell lung cancer (NSCLC). We aimed to evaluate the performance and quality of AI algorithms that use radiomics features in predicting EGFR mutation status in patient with NSCLC. MATERIALS AND METHODS: We searched PubMed (Medline), EMBASE, Web of Science, and IEEExplore for studies published up to February 28, 2022. Studies utilizing an AI algorithm (either conventional machine learning [cML] and deep learning [DL]) for predicting EGFR mutations in patients with NSLCL were included. We extracted binary diagnostic accuracy data and constructed a bivariate random-effects model to obtain pooled sensitivity, specificity, and 95% confidence interval. This study is registered with PROSPERO, CRD42021278738. RESULTS: Our search identified 460 studies, of which 42 were included. Thirty-five studies were included in the meta-analysis. The AI algorithms exhibited an overall area under the curve (AUC) value of 0.789 and pooled sensitivity and specificity levels of 72.2% and 73.3%, respectively. The DL algorithms outperformed cML in terms of AUC (0.822 vs. 0.775) and sensitivity (80.1% vs. 71.1%), but had lower specificity (70.0% vs. 73.8%, p-value < 0.001) compared to cML. Subgroup analysis revealed that the use of positron-emission tomography/computed tomography, additional clinical information, deep feature extraction, and manual segmentation can improve diagnostic performance. CONCLUSION: DL algorithms can serve as a novel method for increasing predictive accuracy and thus have considerable potential for use in predicting EGFR mutation status in patient with NSCLC. We also suggest that guidelines on using AI algorithms in medical image analysis should be developed with a focus on oncologic radiomics.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Inteligência Artificial , Receptores ErbB/genética , Mutação/genética
11.
J Exp Clin Cancer Res ; 42(1): 346, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38124207

RESUMO

BACKGROUND: Atypical teratoid rhabdoid tumors (ATRT) is a rare but aggressive malignancy in the central nervous system, predominantly occurring in early childhood. Despite aggressive treatment, the prognosis of ATRT patients remains poor. RRM2, a subunit of ribonucleotide reductase, has been reported as a biomarker for aggressiveness and poor prognostic conditions in several cancers. However, little is known about the role of RRM2 in ATRT. Uncovering the role of RRM2 in ATRT will further promote the development of feasible strategies and effective drugs to treat ATRT. METHODS: Expression of RRM2 was evaluated by molecular profiling analysis and was confirmed by IHC in both ATRT patients and PDX tissues. Follow-up in vitro studies used shRNA knockdown RRM2 in three different ATRT cells to elucidate the oncogenic role of RRM2. The efficacy of COH29, an RRM2 inhibitor, was assessed in vitro and in vivo. Western blot and RNA-sequencing were used to determine the mechanisms of RRM2 transcriptional activation in ATRT. RESULTS: RRM2 was found to be significantly overexpressed in multiple independent ATRT clinical cohorts through comprehensive bioinformatics and clinical data analysis in this study. The expression level of RRM2 was strongly correlated with poor survival rates in patients. In addition, we employed shRNAs to silence RRM2, which led to significantly decrease in ATRT colony formation, cell proliferation, and migration. In vitro experiments showed that treatment with COH29 resulted in similar but more pronounced inhibitory effect. Therefore, ATRT orthotopic mouse model was utilized to validate this finding, and COH29 treatment showed significant tumor growth suppression and prolong overall survival. Moreover, we provide evidence that COH29 treatment led to genomic instability, suppressed homologous recombinant DNA damage repair, and subsequently induced ATRT cell death through apoptosis in ATRT cells. CONCLUSIONS: Collectively, our study uncovers the oncogenic functions of RRM2 in ATRT cell lines, and highlights the therapeutic potential of targeting RRM2 in ATRT. The promising effect of COH29 on ATRT suggests its potential suitability for clinical trials as a novel therapeutic approach for ATRT.


Assuntos
Neoplasias do Sistema Nervoso Central , Tumor Rabdoide , Animais , Pré-Escolar , Humanos , Camundongos , Apoptose , Neoplasias do Sistema Nervoso Central/metabolismo , Reparo do DNA , Inibidores Enzimáticos/uso terapêutico , Tumor Rabdoide/tratamento farmacológico , Tumor Rabdoide/genética , Tumor Rabdoide/metabolismo
12.
Adv Sci (Weinh) ; 10(35): e2206190, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37946608

RESUMO

Epithelial cells are in continuous dynamic biochemical and physical interaction with their extracellular environment. Ultimately, this interplay guides fundamental physiological processes. In these interactions, cells generate fast local and global transients of Ca2+ ions, which act as key intracellular messengers. However, the mechanical triggers initiating these responses have remained unclear. Light-responsive materials offer intriguing possibilities to dynamically modify the physical niche of the cells. Here, a light-sensitive azobenzene-based glassy material that can be micropatterned with visible light to undergo spatiotemporally controlled deformations is used. Real-time monitoring of consequential rapid intracellular Ca2+ signals reveals that the mechanosensitive cation channel Piezo1 has a major role in generating the Ca2+ transients after nanoscale mechanical deformation of the cell culture substrate. Furthermore, the studies indicate that Piezo1 preferably responds to shear deformation at the cell-material interphase rather than to absolute topographical change of the substrate. Finally, the experimentally verified computational model suggests that Na+ entering alongside Ca2+ through the mechanosensitive cation channels modulates the duration of Ca2+ transients, influencing differently the directly stimulated cells and their neighbors. This highlights the complexity of mechanical signaling in multicellular systems. These results give mechanistic understanding on how cells respond to rapid nanoscale material dynamics and deformations.


Assuntos
Células Epiteliais , Mecanotransdução Celular , Mecanotransdução Celular/fisiologia , Células Cultivadas , Cátions
13.
Front Genet ; 14: 1248338, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37900180

RESUMO

Background: Limb-girdle muscular dystrophy (LGMD) is a group of inherited neuromuscular disorders characterized by atrophy and weakness in the shoulders and hips. Over 30 subtypes have been described in five dominant (LGMD type 1 or LGMDD) and 27 recessive (LGMD type 2 or LGMDR). Each subtype involves a mutation in a single gene and has high heterogeneity in age of onset, expression, progression, and prognosis. In addition, the lack of understanding of the disease and the vague, nonspecific symptoms of LGMD subtypes make diagnosis difficult. Even as next-generation sequencing (NGS) genetic testing has become commonplace, some patients remain undiagnosed for many years. Methods: To identify LGMD-associated mutations, Targeted sequencing was performed in the patients and Sanger sequencing was performed in patients and family members. The in silico analysis tools such as Fathmm, M-CAP, Mutation Taster, PolyPhen 2, PROVEAN, REVEL, SIFT, MaxEntScan, Spliceailookup, Human Splicing Finder, NetGene2, and Fruitfly were used to predict the influence of the novel mutations. The pathogenicity of the mutation was interpreted according to the ACMG guidelines. Results: In this study, six patients from four different Vietnamese families were collected for genetic analysis at The Center for Gene and Protein Research and The Department of Molecular Pathology Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam. Based on clinical symptoms and serum creatine kinase (CK) levels, the patients were diagnosed with limb-girdle muscular dystrophies. Five mutations, including four (c.229C>T, p.Arg77Cys; exon one to three deletion; c.983 + 5G>C; and c.257_258insTGGCT, p.Phe88Leufs*125) in the SGCA gene and one (c.946-4_946-1delACAG) in the CAPN3 gene, were detected in six LGMD patients from four unrelated Vietnamese families. Two homozygous mutations (c.983 + 5G>C and c.257_258insTGGCT) in the SGCA gene were novel. These mutations were identified as the cause of the disease in the patients. Conclusion: Our results contribute to the general understanding of the etiology of the disease and provide the basis for definitive diagnosis and support genetic counseling and prenatal screening.

14.
Contemp Oncol (Pozn) ; 27(2): 71-79, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37794989

RESUMO

Introduction: This study aimed to evaluate the treatment outcomes of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy alone or in combination with locoregional brain therapy for advanced EGFR-mutant non-small cell lung cancer (NSCLC) patients with brain metastases. Material and methods: A retrospective study involving 72 advanced EGFR-mutant NSCLC patients with brain metastases at the Vietnam National Cancer Hospital were conducted. Patients were divided into 2 groups: EGFR-TKI (erlotinib) monotherapy and EGFR-TKI combined with locoregional therapy (γ knife surgery - GKS or whole-brain radiation therapy). Evaluation criteria included clinical and laboratory characteristics, central nervous system (CNS) progression time, progression-free survival (PFS), overall survival (OS), T790M mutation rate, and adverse events. Results: Epidermal growth factor receptor tyrosine kinase inhibitor monotherapy patients had better performance status (PS), fewer CNS symptoms, and significantly fewer brain metastases (p < 0.05). Median PFS and OS were 11 and 25 months, respectively, in both groups. Patients with PS 0-1 had longer median PFS (15 months) than those with PS 2 (7 months) (p = 0.039). Exon 19 deletion patients in both groups had longer median OS (26 months) than those with L858R exon 21 (15 months) (p = 0.023). Patients with T790M mutation who received osimertinib after progression had longer median OS (41 months vs. 23 months, p = 0.0001). Median time to CNS progression was 13.9 months (48 patients). Longer time to CNS progression correlated with longer OS (R2 = 0.89). Conclusions: Epidermal growth factor receptor tyrosine kinase inhibitor therapy, with or without locoregional therapy, is effective for advanced EGFR-mutant NSCLC patients with brain metastases. Exon 19 deletion patients had better prognosis.

15.
Science ; 381(6661): eadg0995, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37651534

RESUMO

Plant mitochondria represent the largest group of respiring organelles on the planet. Plant mitochondrial messenger RNAs (mRNAs) lack Shine-Dalgarno-like ribosome-binding sites, so it is unknown how plant mitoribosomes recognize mRNA. We show that "mitochondrial translation factors" mTRAN1 and mTRAN2 are land plant-specific proteins, required for normal mitochondrial respiration chain biogenesis. Our studies suggest that mTRANs are noncanonical pentatricopeptide repeat (PPR)-like RNA binding proteins of the mitoribosomal "small" subunit. We identified conserved Adenosine (A)/Uridine (U)-rich motifs in the 5' regions of plant mitochondrial mRNAs. mTRAN1 binds this motif, suggesting that it is a mitoribosome homing factor to identify mRNAs. We demonstrate that mTRANs are likely required for translation of all plant mitochondrial mRNAs. Plant mitochondrial translation initiation thus appears to use a protein-mRNA interaction that is divergent from bacteria or mammalian mitochondria.


Assuntos
Mitocôndrias , Iniciação Traducional da Cadeia Peptídica , Proteínas de Plantas , RNA Mensageiro , Animais , Sítios de Ligação , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas de Plantas/classificação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Mitocondrial/genética , RNA Mitocondrial/metabolismo , RNA de Plantas/genética , RNA de Plantas/metabolismo , Sequência Conservada
16.
Spine (Phila Pa 1976) ; 48(18): 1289-1294, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37389986

RESUMO

STUDY DESIGN: A single-center prospective observational study. OBJECTIVE: To clarify the usefulness of a novel scoliosis screening method using a 3-dimensional (3D) human fitting application and a specific bodysuit. SUMMARY OF BACKGROUND DATA: Several scoliosis screening methods, such as scoliometer and Moiré topography, are available for detecting scoliosis. In the present study, a novel screening method for scoliosis using a 3D human fitting application and a specific bodysuit was developed. PATIENTS AND METHODS: Patients with scoliosis or suspected scoliosis, patients with non-scoliosis, and healthy volunteers were enrolled. They were divided into "non-scoliosis" and "scoliosis" groups. The scoliosis group was further subdivided into "mild," "moderate," and "severe-scoliosis" groups. Patients' characteristics and Z values, which were calculated by a 3D virtual human body model created by a 3D human fitting application and a specific bodysuit to evaluate trunk asymmetry caused by scoliosis, were compared between the non-scoliosis and scoliosis groups or among the non, mild, moderate and severe-scoliosis groups. Finally, the optimal cutoff of the Z value was determined to detect moderate to severe scoliosis using receiver operating characteristic curve analysis. RESULTS: A total of 101 patients were included. The non-scoliosis group consisted of 47 patients, and the scoliosis group included 54 patients, with 11, 31, and 12 patients in the mild, moderate, and severe-scoliosis groups, respectively. The scoliosis group showed a significantly higher Z value than the non-scoliosis group. The moderate or severe-scoliosis group had a significantly higher Z value than the non or mild-scoliosis group. The receiver operating characteristic curve analysis revealed that the optimal cutoff of the Z value was 19.9 mm (sensitivity, 95.3% and specificity, 58.6%). CONCLUSION: A novel scoliosis screening method consisting of a 3D human fitting application and a specific bodysuit may be useful for detecting moderate to severe scoliosis.


Assuntos
Escoliose , Humanos , Escoliose/diagnóstico por imagem , Programas de Rastreamento/métodos , Estudos Prospectivos , Curva ROC , Imageamento Tridimensional
17.
World Neurosurg ; 175: e796-e803, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37061031

RESUMO

BACKGROUND: Spetzler-Martin (SM) grade III arteriovenous malformations (AVMs) show angioarchitecture heterogeneity and lack a clearly defined treatment strategy. This study aims to evaluate outcomes after treatment of SM grade III AVMs with Gamma Knife radiosurgery (GKRS). METHODS: A single-institution retrospective analysis was conducted of 307 patients with SM grade III AVMs undergoing GKRS between October 2006 and December 2020 with follow-up times of at least 24 months. SM grade III AVMs were classified into 4 subtypes: IIIA (S1E1V1), IIIB (S2E0V1), subtype IIIC (S2E1V0), and IIID (S3E0V0). RESULTS: Over a median follow-up time of 50.3 months, complete AVM obliteration was achieved in 211 patients (68.7%). Complete obliteration rates in subtypes IIIA, IIIB, IIIC, and IIID were 80.8%, 55.4%, 53.4%, and 25.0%, respectively. Annual post-GKRS hemorrhage risk was 0.8%. Significant radiosurgery-induced imaging changes occurred in 7 patients (2.3%). Three variables were identified as predictors of obliteration in final forward stepwise regression models, including volume of AVM (B = -0.011; P < 0.001), age (B = -0.004; P = 0.024), and previous AVM hemorrhage (B = 0.187; P = 0.077). CONCLUSIONS: GKRS is a safe and effective treatment for SM grade III AVMs, particularly subtype IIIA (S1E1V1). AVM volume is the key predictor of post-GKRS obliteration.


Assuntos
Malformações Arteriovenosas Intracranianas , Malformações do Sistema Nervoso , Radiocirurgia , Humanos , Radiocirurgia/métodos , Estudos Retrospectivos , Malformações Arteriovenosas Intracranianas/radioterapia , Malformações Arteriovenosas Intracranianas/cirurgia , Resultado do Tratamento , Encéfalo , Malformações do Sistema Nervoso/cirurgia , Seguimentos
18.
ACG Case Rep J ; 10(1): e00963, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36699184

RESUMO

Erdheim-Chester disease (ECD) is an exceedingly rare and aggressive disease characterized by foamy CD68 + CDa-histiocytic infiltration into multiple tissues and organs. Only 1,500 cases have been diagnosed since 1930 when ECD was first described. Biliary tract involvement of ECD has only been reported in the literature once. We report a case of ECD causing extrahepatic biliary obstruction without significant bile duct dilation, mimicking primary sclerosing cholangitis or IgG4 disease.

19.
Am J Ophthalmol ; 247: 18-24, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36347276

RESUMO

PURPOSE: To evaluate myopia progression with highly aspherical lenslet (HAL) spectacles vs conventional single vision (SV) spectacles. DESIGN: Prospective, double-blind, single-center, randomized, cross-over trial. METHOD: A total of 119 Vietnamese children (7-13 years of age, spherical equivalent refractive error [SE] = -0.75 to -4.75D) were randomized to wear either HAL or SV, and after 6 months (stage 1) crossed over to the other lens for another 6 months (stage 2). At the end of stage 2, both groups wore HAL for a further 6 months. In the order that lenses were worn at each stage, group 1 was designated HSH (HAL-SV-HAL) and group 2 SHH (SV-HAL-HAL). The main outcome measures were a comparison between HAL and SV for change (Δ) in SE and axial length (AL) during each stage; and a comparison of ΔSE/AL with SV between HSH and SHH groups to determine whether myopia rebounded when switched from HAL to SV (HSH group). RESULTS: Myopia progressed more slowly with HAL than with SV during stages 1 and 2 (SEΔ stage 1: -0.21 vs -0.27D, P = .317, stage 2: -0.05 vs -0.32D, P < .001; ALΔ stage 1: 0.07 vs 0.14 mm, P = .004; stage 2: 0.04 vs 0.17 mm, P < .001). ΔSE/AL with SV was not different between the HSH and SHH groups (ΔSE -0.33 ± 0.27D vs -0.27 ± 0.42D, P = .208; ΔAL 0.17 ± 0.13mm vs 0.13 ± 0.15 mm, P = .092). An average of 14 hours per day of lens wear was reported with both lenses. CONCLUSIONS: In this cross-over trial, intergroup and intragroup comparisons indicate that HAL slows myopia. Children were compliant with lens wear, and data were not suggestive of rebound when patients were switched from HAL to SV.


Assuntos
Miopia , Oftalmologia , Criança , Humanos , Recém-Nascido , Lactente , Refração Ocular , Óculos , Estudos Prospectivos
20.
Cornea Open ; 2(4)2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38855500

RESUMO

Purpose: Conjunctivitis epidemics and pandemics remain a global burden. This study aims to comprehensively identify pathogens associated with conjunctivitis in Vietnam. Methods: Patients with acute conjunctivitis presented to an outpatient clinic in Ho Chi Minh City, Vietnam, were enrolled from September 2022 to March 2023. Swabs were obtained from conjunctiva and anterior nares of all patients. Unbiased RNA deep sequencing (RNA-seq) was used to identify any replicating pathogens in the samples. Results: Samples from 35 patients were analyzed. A pathogen was identified in 80% of the patients. 72% (95% confidence interval: 54% to 85%) were infected with either HAdV-D or HAdV-B. RNA viruses detected were rhinoviruses and human coronavirus 229E. Bacteria etiologies included Streptococcus pneumoniae, Hemophilus influenza, and Pseudomonas spp. One patient had co-infection of rhinovirus A and HAdV-B. Vittaforma corneae, a fungus, was identified in one patient. Corneal sub-epithelial infiltrates, pseudomembranes, or pre-auricular lymphadenopathy were not reported in any patient. Conclusions: Human adenoviruses are the common circulating pathogens associated with infectious conjunctivitis in Vietnam. HAdV species, however, appear to vary between geographic locations within Vietnam. Other under-recognized pathogens identified in this study, such as RNA viruses, suggest broader pathogen surveillance may be beneficial.

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