Development and validation of Mayaro virus with luciferase reporter genes as a tool for antiviral assays.

Arboviruses are etiological agents in an extensive group of emerging diseases with great clinical relevance in Brazil, due to the wide distribution of their vectors and the favorable environmental conditions. Among them, the Mayaro virus (MAYV) has drawn attention since its emergence as the etiologic agent of Mayaro fever, a highly debilitating disease. To study viral replication and identify new drug candidates, traditional antiviral assays based on viral antigens and/or plaque assays have been demonstrating low throughput, making it difficult to carry out larger-scale assays. Therefore, we developed and characterized two DNA-launched infectious clones reporter viruses based on the MAYV strain BeAr 20290 containing the reporter genes of firefly luciferase (FLuc) and nanoluciferase (NLuc), designated as MAYV-firefly and MAYV-nanoluc, respectively. The viruses replicated efficiently with similar properties to the parental wild-type MAYV, and luminescence expression levels reflected viral replication. Reporter genes were also preserved during passage in cell culture, remaining stably expressed for one round of passage for MAYV-firefly and three rounds for MAYV-nanoluc. Employing the infectious clone, we described the effect of Rimantadine, an FDA-approved Alzheimer's drug, as a repurposing agent for MAYV but with a broad-spectrum activity against Zika virus infection. Additionally, we validated MAYV-nanoluc as a tool for antiviral drug screening using the compound EIDD-2749 (4'-Fluorouridine), which acts as an inhibitor of alphavirus RNA-dependent RNA polymerase.

The effects of art therapy interventions on anxiety in children and adolescents: A meta-analysis.

OBJECTIVE: This study aimed to assess the effects of art therapy on anxiety among children and adolescents. METHODS: We searched several databases, including PubMed, Web of Science, Embase (via Ovid), PsychINFO (through EBSCO), and The Cochrane Library, comprising the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials. Additionally, Chinese databases such as CNKI (China National Knowledge Infrastructure) and Wan Fang Data were explored from their beginnings until October 22, 2023. Studies that investigated the impact of art therapy on anxiety compared to a control group were included. The methodological quality of these randomized controlled trials was evaluated using the Cochrane Handbook's risk of bias instrument. RESULTS: Six studies involving 422 participants were included. The findings indicated a notable decrease in anxiety symptoms due to art therapy, with a Standardized Mean Difference (SMD) of -1.42, 95% Confidence Interval (95%CI -2.33, -0.51), p < 0.002. Notably, there was pronounced heterogeneity, as evidenced by Tau2 = 1.41, Chi2 = 101.19, df = 6, and I² = 94%, with Z = 3.06. CONCLUSION: Art therapy significantly improved the anxiety symptoms of children and adolescents, positioning it as an effective means of treating anxiety.

The effects of art therapy interventions on anxiety in children and adolescents: A meta-analysis

Abstract Objective: This study aimed to assess the effects of art therapy on anxiety among children and adolescents. Methods: We searched several databases, including PubMed, Web of Science, Embase (via Ovid), PsychINFO (through EBSCO), and The Cochrane Library, comprising the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials. Additionally, Chinese databases such as CNKI (China National Knowledge Infrastructure) and Wan Fang Data were explored from their beginnings until October 22, 2023. Studies that investigated the impact of art therapy on anxiety compared to a control group were included. The methodological quality of these randomized controlled trials was evaluated using the Cochrane Handbook's risk of bias instrument. Results: Six studies involving 422 participants were included. The findings indicated a notable decrease in anxiety symptoms due to art therapy, with a Standardized Mean Difference (SMD) of -1.42, 95% Confidence Interval (95%CI -2.33, -0.51), p < 0.002. Notably, there was pronounced heterogeneity, as evidenced by Tau2 = 1.41, Chi2 = 101.19, df = 6, and I2 = 94%, with Z = 3.06. Conclusion: Art therapy significantly improved the anxiety symptoms of children and adolescents, positioning it as an effective means of treating anxiety.

Diagnostic value of a computer-assisted diagnosis system for the ultrasound features in thyroid nodules

ABSTRACT Objective: To explore the diagnostic value of the TUIAS (SW_TH01/II) computer-aided diagnosis (CAD) software system for the ultrasound Thyroid Imaging Reporting and Data System (TI-RADS) features in thyroid nodules. Materials and methods: This retrospective study enrolled patients with thyroid nodules in Shanghai East Hospital between January 2017 and October 2021. The novel CAD software (SW_TH01/II) and three sonographers performed a qualitative analysis of the ultrasound TI-RADS features in aspect ratio, margin irregularity, margin smoothness, calcification, and echogenicity of the thyroid nodules. Results: A total of 225 patients were enrolled. The accuracy, sensitivity, and specificity of the CAD software in "aspect ratio" were 95.6%, 96.2%, and 95.4%, in "margin irregularity" were 90.7%, 90.5%, and 90.9%, in "margin smoothness" were 85.8%, 88.5%, and 83.0%, in "calcification" were 83.6%, 81.7%, and 82.0%, in "homogeneity" were 88.9%, 90.6%, and 82.2%, in "major echo" were 85.3%, 88.0%, and 85.4%, and in "contains very hypoechoic echo" were 92.0%, 90.0%, and 92.4%. The analysis time of the CAD software was significantly shorter than for the sonographers (2.7 ± 1.6 vs. 29.7 ± 12.7 s, P < 0.001). Conclusion: The CAD system achieved high accuracy in describing thyroid nodule features. It might assist in clinical thyroid nodule analysis.

Diagnostic value of a computer-assisted diagnosis system for the ultrasound features in thyroid nodules.

Objective: To explore the diagnostic value of the TUIAS (SW_TH01/II) computer-aided diagnosis (CAD) software system for the ultrasound Thyroid Imaging Reporting and Data System (TI-RADS) features in thyroid nodules. Materials and methods: This retrospective study enrolled patients with thyroid nodules in Shanghai East Hospital between January 2017 and October 2021. The novel CAD software (SW_TH01/II) and three sonographers performed a qualitative analysis of the ultrasound TI-RADS features in aspect ratio, margin irregularity, margin smoothness, calcification, and echogenicity of the thyroid nodules. Results: A total of 225 patients were enrolled. The accuracy, sensitivity, and specificity of the CAD software in "aspect ratio" were 95.6%, 96.2%, and 95.4%, in "margin irregularity" were 90.7%, 90.5%, and 90.9%, in "margin smoothness" were 85.8%, 88.5%, and 83.0%, in "calcification" were 83.6%, 81.7%, and 82.0%, in "homogeneity" were 88.9%, 90.6%, and 82.2%, in "major echo" were 85.3%, 88.0%, and 85.4%, and in "contains very hypoechoic echo" were 92.0%, 90.0%, and 92.4%. The analysis time of the CAD software was significantly shorter than for the sonographers (2.7 ± 1.6 vs. 29.7 ± 12.7 s, P < 0.001). Conclusion: The CAD system achieved high accuracy in describing thyroid nodule features. It might assist in clinical thyroid nodule analysis.

Tracing global N2O emission mitigation strategies through trade networks.

Nitrous oxide (N2O) is the third most potent greenhouse gas (GHG) and the most important ozone depleting substance. But how global N2O emissions are connected through the interwoven trade network remains unclear. This paper attempts to specifically trace anthropogenic N2O emissions via global trade networks using a multi-regional input-output model and a complex network model. Nearly one quarter of global N2O emissions can be linked to products traded internationally in 2014. The top 20 economies contribute to about 70% of the total embodied N2O emission flows. In terms of the trade embodied emissions classified by sources, cropland-, livestock-, chemistry-, and other industries-related embodied N2O emissions account for 41.9%, 31.2%, 19.9%, and 7.0%, respectively. Clustering structure of the global N2O flow network is revealed by the regional integration of 5 trading communities. Hub economies such as mainland China and the USA are collectors and distributors, and some emerging countries, such as Mexico, Brazil, India, and Russia, also exhibit dominance in different kinds of networks. This study selects the cattle sector to further verify that low production-side emission intensities and trade cooperation can lead to N2O emission reduction. In view of the impact of trade networks on global N2O emissions, achieving N2O emission reduction calls for vigorous international cooperation.

Challenges in the Clinical Recognition of Acute Flaccid Myelitis and its Implications.

OBJECTIVES: To explore the challenges in diagnosing acute flaccid myelitis (AFM) and evaluate clinical features and treatment paradigms associated with under recognition. STUDY DESIGN: This was a retrospective multicenter study of pediatric patients (≤18 years) who were diagnosed with AFM from 2014 to 2018 using the Centers for Disease Control and Prevention's case definition. RESULTS: In 72% of the cases (126 of 175), AFM was not considered in the initial differential diagnosis (n = 108; 61.7%) and/or the patient was not referred for acute care (n = 90; 51.4%) at the initial clinical encounter, and this did not improve over time. Although many features of the presentation were similar in those initially diagnosed with AFM and those who were not; preceding illness, constipation, and reflexes differed significantly between the 2 groups. Patients with a non-AFM initial diagnosis more often required ventilatory support (26.2% vs 12.2%; OR, 0.4; 95% CI, 0.2-1.0; P = .05). These patients received immunomodulatory treatment later (3 days vs 2 days after neurologic symptom onset; 95% CI, -2 to 0; P = .05), particularly intravenous immunoglobulin (5 days vs 2 days; 95% CI, -4 to -2; P < .001). CONCLUSIONS: Delayed recognition of AFM is concerning because of the risk for respiratory decompensation and need for intensive care monitoring. A non-AFM initial diagnosis was associated with delayed treatment that could have a clinical impact, particularly as new treatment options emerge.

Meniscus injuries under high-intensity training in cycling athletes / Lesões no menisco sob treinamento de alta intensidade em atletas de ciclismo / Lesiones de menisco bajo entrenamiento de alta intensidad en atletas de ciclismo

ABSTRACT Introduction: Due to the high intensity and speed of cycling, a high technical and tactical level, physical quality, and psychological quality are required of athletes. Meniscal injuries are common in cyclists. In particular, chronic meniscal injuries are usually caused by an accumulation of fatigue or untimely and incomplete treatment of acute sports injuries. Objective: Analyze the protective factors and methods for meniscal injuries in cyclists. Methods: Volunteer male cyclists were selected for a questionnaire that investigated the athletes' meniscal injuries. The data collected were statistically analyzed. Results: There were 6 cases of right knee meniscus injury in athletes; these data accounted for 75% of the injuries. Left meniscus injuries accounted for 2 cases. There was one case of medial injury in both knees. The corresponding preventive measures are presented according to the cause of the injury. Conclusion: Causes of meniscal injuries in cyclists include insufficient knee strength, inadequate training methods, physical fatigue, and long-term localized effort. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Devido à alta intensidade e velocidade do ciclismo, é exigido um alto nível técnico e tático, qualidade física e qualidade psicológica dos atletas. Lesões meniscais são comuns em ciclistas. Em particular, as lesões meniscais crônicas são geralmente causadas por um acúmulo de fadiga ou tratamento inoportuno e incompleto de lesões esportivas agudas. Objetivo: Analisar os fatores e métodos de proteção para lesões meniscais em ciclistas. Métodos: Ciclistas do sexo masculino voluntários foram selecionados para um questionário que investigou as lesões meniscais dos atletas. Os dados coletados foram analisados estatisticamente. Resultados: Houve 6 casos de lesão meniscal do joelho direito em atleta, esses dados são responsáveis por 75% dos danos. Lesões no menisco esquerdo representaram 2 casos. Houve um caso de lesão medial em ambos os joelhos. As medidas preventivas correspondentes são apresentadas de acordo com a causa da lesão. Conclusão: As causas das lesões meniscais em ciclistas incluem força insuficiente no joelho, métodos de treinamento inadequados, fadiga física e esforço localizado a longo prazo. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Debido a la alta intensidad y velocidad del ciclismo, se exige a los deportistas un alto nivel técnico y táctico, calidad física y calidad psicológica. Las lesiones de menisco son comunes en los ciclistas. En particular, las lesiones crónicas de menisco suelen ser causadas por una acumulación de fatiga o por un tratamiento inoportuno e incompleto de las lesiones deportivas agudas. Objetivo: Analizar los factores y métodos de protección de las lesiones meniscales en ciclistas. Métodos: Se seleccionaron ciclistas masculinos voluntarios para un cuestionario que investigaba las lesiones meniscales de los atletas. Los datos recogidos se analizaron estadísticamente. Resultados: Hubo 6 casos de lesiones de menisco de la rodilla derecha en atletas, estos datos representaron el 75% de las lesiones. Las lesiones del menisco izquierdo representaron 2 casos. Hubo un caso de lesión medial en ambas rodillas. Las medidas preventivas correspondientes se presentan según la causa de la lesión. Conclusión: Las causas de las lesiones de menisco en los ciclistas incluyen una fuerza insuficiente de la rodilla, métodos de entrenamiento inadecuados, fatiga física y esfuerzos localizados a largo plazo. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Optimization of density and durability of pellets using the response surface methodology in ultrasonic vibration-assisted pelleting of corn stover

Top-quality pellets can significantly increase density and durability of agricultural residues, reducing logistic costs. However, these pellets depend on numerous parameters, including feedstock properties and production conditions. To ensure high-quality pellets, a single-factor experiment and the response surface methodology were used to investigate the effects of particle size, moisture content, molding pressure, pelleting time, ultrasonic power, and interaction effects between variables on density and durability of pellets for ultrasonic vibration-assisted pelleting of corn stover. The response surface models between variables and response were established. The results showed that all variables affect the density and durability of pellets. An optimal condition for density and durability was obtained, and a further experiment was conducted to validate the values. The results suggested that desirability (0.999) under optimal conditions confirmed the validation of models. The optimal combination of process parameters included particle size of 1.5 mm, moisture content of 10 %, molding pressure of 379 kPa, pelleting time of 80 s, ultrasonic power of 250 W, with values of 1,381.14 kg m-3 and 97.58 % for density and durability of pellets, respectively.

High expression of HOXA4 in patients with glioma indicates unfavorable clinical outcomes.

HOXA4 is a novel oncogene that has been observed in many kinds of tumors, but its role during glioma carcinogenesis and its clinical significance in diagnosing and prognosis human glioma remains unknown. In the present study, the Chinese Glioma Atlas (CGGA)-RNA sequencing database, CGGA microarray, and The Cancer Genome Atlas (TCGA)-RNA seq data from 1674 glioma patients were obtained from online databases and analyzed using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) to detect changes in the expression level of HOXA4 and characterize the relationship between HOXA4 and the clinical characteristics and prognosis of patients with glioma. Gene set enrichment analysis (GSEA) was used to reveal how HOXA4 regulates tumor-related pathways. HOXA4 mRNA levels in glioma tissue were higher than those in adjacent brain tissue. HOXA4 expression was also closely related to the clinical and molecular characteristics of gliomas, such as tumor grade and isocitrate dehydrogenase (IDH) mutation. Functional enrichment analysis revealed that HOXA4 could regulate cancer-related signal pathways, such as Cell cycle, Cell adhesion molecules cams, and JAK/STAT signaling pathway. Results of in vitro experiments confirmed that knockdown of HOXA4 blocks the cell cycle pathway and inhibits the proliferation, invasion and chemotherapy resistance in gliomas. We concluded that HOXA4 was an independent risk factor for glioma and may have clinical diagnostic potential. Meanwhile, our findings revealed that HOXA4 could be used as a biomarker for glioma diagnosis and treatment.

Two-step extinction of Late Cretaceous marine vertebrates in northern Gulf of Mexico prolonged biodiversity loss prior to the Chicxulub impact.

Recent studies on mass extinctions are often based on the global fossil record, but data from selected paleogeographic regions under a relatively constant paleoenvironmental setting can also provide important information. Eighty-nine marine vertebrate species, including cartilaginous and bony fish and marine reptiles, from northern Gulf of Mexico - located about 500 km from the Chicxulub crater - offer a unique opportunity to determine an extinction process during the last 20 million years of the Late Cretaceous. Our diversity data show two separate extinction events: (i) the 'Middle Campanian Crisis' (about 77 Mya) and (ii) the end-Maastrichtian (66 Mya) events. Whether this stepwise pattern of extinctions occurred locally or globally cannot be determined at present due to the lack of a dataset of the marine vertebrate record for reliable comparison. However, this stepwise pattern including the Middle Campanian and end-Maastrichtian events for, at least, a 13 million-year interval indicates long-term global marine environmental changes (e.g., regression, ocean water chemistry change). Because most Cretaceous marine vertebrates already disappeared in the Gulf of Mexico prior to the latest Maastrichtian, the Chicxulub Impact may not be considered as the most devastating extinction event for the community.

Quantifying global CH4 and N2O footprints.

This study aims to quantify global CH4 and N2O footprints in 2012 in terms of 181 economies and 20 world regions based on the official national emission accounts from the UNFCCC database and the global multi-region input-output accounts from the EORA database. Global total CH4 and N2O emissions increased by 15.0% in 2012 compared to 1990, mainly driven by increasing demands of agricultural and energy products. Mainland China, Western Europe, the USA, Southeast Asia and Sub-Saharan Africa were identified as the largest five CH4 footprint contributors (55.6% of the global total), while Mainland China, the USA, Western Europe, Brazil and Sub-Saharan Africa as the largest N2O footprint contributors (59.2% of the global total). In most developed economies, the CH4 and N2O footprints were much higher than their emissions on the production side, but opposite picture is observed in emerging economies. 36.4% and 24.8% of the global CH4 and N2O emissions in 2012 were associated with international trade, respectively. Substantial energy-related CH4 and agricultural CH4 and N2O emissions were transferred from developed countries to developing countries. Several nations within Kyoto targets have reduced their CH4 and N2O emissions significantly between 1990 and 2012, but the generally-believed success is challenged when viewing from the consumption side. Mainland China, Southeast Asia, Sub-Saharan Africa, Brazil, Middle East and India witnessed prominent increase of CH4 and N2O footprints in the same period. The structure and spatial patterns of global CH4 and N2O footprints shed light on the role of consumption-side actions and international cooperation for future non-CO2 GHG emission reduction.

Endoscopic full-thickness resection for gastric gastrointestinal stromal tumor originating from the muscularis propria.

OBJECTIVE: This study retrospectively reviewed 46 cases of gastric gastrointestinal stromal tumors treated by endoluminal endoscopic full-thickness resection (EFR) microsurgery in our gastrointestinal endoscopy center. We aimed to evaluate the EFR for the treatment of gastric gastrointestinal stromal tumors originating from the muscularis propria. METHODS: A total of 46 patients with gastric gastrointestinal stromal tumors originated from the muscularis propria layer from January 2012 to June 2015 were treated with EFR. The patients were followed up with gastroscope and computed tomography (CT) for evaluation of therapeutic effect and safety. RESULTS: EFR was successfully accomplished to remove all tumors in 46 patients. The mean procedure time was 82.5±39.8min (56-188min). Except in 3 leiomyomas, pathological examination confirmed gastrointestinal stromal tumor (GIST) in 43 cases. None of the patients had occurred bleeding, peritonitis and other complications after EFR. Thereafter, all patients were followed up with gastro-scope after 1, 6,12 months. CONCLUSIONS: EFR is effective and safe for patients with gastric gastrointestinal stromal tumors originated from muscularis propria layer and has the advantage of less invasive treatment and higher tumor resection rate. It should be considered for further application.

Long-Term Parathyroid Hormone 1-34 Replacement Therapy in Children with Hypoparathyroidism.

OBJECTIVE: To determine whether multiple daily injections of parathyroid hormone (PTH) 1-34 are safe and effective as long-term therapy for children with hypoparathyroidism. STUDY DESIGN: Linear growth, bone accrual, renal function, and mineral homeostasis were studied in a long-term observational study of PTH 1-34 injection therapy in 14 children. METHODS: Subjects were 14 children with hypoparathyroidism attributable to autoimmune polyglandular syndrome type 1 (N = 5, ages 7-12 years) or calcium receptor mutation (N = 9, ages 7-16 years). Mean daily PTH 1-34 dose was 0.75 ± 0.15 µg/kg/day. Treatment duration was 6.9 ± 3.1 years (range 1.5-10 years). Patients were evaluated semiannually at the National Institutes of Health Clinical Center. RESULTS: Mean height velocity and lumbar spine, whole body, and femoral neck bone accretion velocities were normal throughout the study. In the first 2 years, distal one-third radius bone accrual velocity was reduced compared with normal children (P < .003). Serum alkaline phosphatase correlated with PTH 1-34 dose (P < .006) and remained normal (235.3 ± 104.8 [SD] U/L, N: 51-332 U/L). Mean serum and 24-hour urine calcium levels were 2.05 ± 0.11 mmol/L (N: 2.05-2.5 mmol/L) and 6.93 ± 1.3 mmol/24 hour (N: 1.25-7.5 mmol/24 hour), respectively-with fewer high urine calcium levels vs baseline during calcitriol and calcium treatment (P < .001). Nephrocalcinosis progressed in 5 of 12 subjects who had repeated renal imaging although renal function remained normal. CONCLUSIONS: Twice-daily or thrice-daily subcutaneous PTH 1-34 injections provided safe and effective replacement therapy for up to 10 years in children with hypoparathyroidism because of autoimmune polyglandular syndrome type 1 or calcium receptor mutation.

Endoscopic full-thickness resection for gastric gastrointestinal stromal tumor originating from the muscularis propria

SUMMARY OBJECTIVE: This study retrospectively reviewed 46 cases of gastric gastrointestinal stromal tumors treated by endoluminal endoscopic full-thickness resection (EFR) microsurgery in our gastrointestinal endoscopy center. We aimed to evaluate the EFR for the treatment of gastric gastrointestinal stromal tumors originating from the muscularis propria. METHODS: A total of 46 patients with gastric gastrointestinal stromal tumors originated from the muscularis propria layer from January 2012 to June 2015 were treated with EFR. The patients were followed up with gastroscope and computed tomography (CT) for evaluation of therapeutic effect and safety. RESULTS: EFR was successfully accomplished to remove all tumors in 46 patients. The mean procedure time was 82.5±39.8min (56-188min). Except in 3 leiomyomas, pathological examination confirmed gastrointestinal stromal tumor (GIST) in 43 cases. None of the patients had occurred bleeding, peritonitis and other complications after EFR. Thereafter, all patients were followed up with gastro-scope after 1, 6,12 months. CONCLUSIONS: EFR is effective and safe for patients with gastric gastrointestinal stromal tumors originated from muscularis propria layer and has the advantage of less invasive treatment and higher tumor resection rate. It should be considered for further application.

RESUMO OBJETIVO: Este estudo revisou retrospectivamente 46 casos de tumores gástricos estromáticos gastrointestinais tratados por microcirurgia endoluminal endoscópica de ressecção completa (EFR) em nosso centro de endoscopia gastrointestinal. Pretendemos avaliar a EFR para o tratamento de tumores gastrointestinais estromáticos originários da muscularis própria. MÉTODOS: Um total de 46 pacientes com tumores gástricos estromáticos gastrointestinais originários da camada muscular própria, de janeiro de 2012 a junho de 2015, foi tratado com EFR. Os pacientes foram acompanhados com gastroscópio e tomografia computadorizada (TC) para avaliação de efeitos terapêuticos e segurança. RESULTADOS: A EFR foi realizada com sucesso para remover todos os tumores em 46 pacientes. O tempo médio de procedimento foi de 82,5±39,8 min (56-188 min). Exceto em três leiomiomas, exame patológico confirmou tumor estromal gastrointestinal (Gist) em 43 casos. Em nenhum paciente ocorreu sangramento, peritonite e outras complicações após EFR. Posteriormente, todos os pacientes foram acompanhados com gastroscópio após um, seis e 12 meses. CONCLUSÕES: A EFR é eficaz e segura para pacientes com tumores gastrointestinais originários da camada muscular própria e tem a vantagem de ser um tratamento menos invasivo e com maior taxa de ressecção tumoral. Deve ser considerada para posterior aplicação.

Potential for Co-Infection of a Mosquito-Specific Flavivirus, Nhumirim Virus, to Block West Nile Virus Transmission in Mosquitoes.

Nhumirim virus (NHUV) is an insect-specific virus that phylogenetically affiliates with dual-host mosquito-borne flaviviruses. Previous in vitro co-infection experiments demonstrated prior or concurrent infection of Aedes albopictus C6/36 mosquito cells with NHUV resulted in a 10,000-fold reduction in viral production of West Nile virus (WNV). This interference between WNV and NHUV was observed herein in an additional Ae. albopictus mosquito cell line, C7-10. A WNV 2K peptide (V9M) mutant capable of superinfection with a pre-established WNV infection demonstrated a comparable level of interference from NHUV as the parental WNV strain in C6/36 and C7-10 cells. Culex quinquefasciatus and Culex pipiens mosquitoes intrathoracically inoculated with NHUV and WNV, or solely with WNV as a control, were allowed to extrinsically incubate the viruses up to nine and 14 days, respectively, and transmissibility and replication of WNV was determined. The proportion of Cx. quinquefasciatus mosquitoes capable of transmitting WNV was significantly lower for the WNV/NHUV group than the WNV control at seven and nine days post inoculation (dpi), while no differences were observed in the Cx. pipiens inoculation group. By dpi nine, a 40% reduction in transmissibility in mosquitoes from the dual inoculation group was observed compared to the WNV-only control. These data indicate the potential that infection of some Culex spp. vectors with NHUV could serve as a barrier for efficient transmissibility of flaviviruses associated with human disease.

Preoperative imatinib for patients with primary unresectable or metastatic/recurrent gastrointestinal stromal tumor.

OBJECTIVES: Despite its rising popularity, reports on the use of preoperative imatinib mesylate (IM) in patients with advanced gastrointestinal stromal tumor (GIST) are limited. This study aims to explore the clinical efficacy of preoperative IM in patients with primarily unresectable or metastatic/recurrent GIST. METHODS: Between September 2009 and February 2014, patients with primarily unresectable or metastatic/recurrent GIST treated by a single medical team were recruited and considered for preoperative IM therapy. Re-examination was conducted regularly and abdominal enhanced CT data, blood biochemistry and responses to IM were recorded. RESULTS: A total of 18 patients were enrolled, including 13 with a primary tumor (7 stomach, 3 small bowel, 2 rectal and 1 pelvic tumor) and 5 with recurrent or metastatic GIST (2 with liver metastasis, 2 with anastomotic recurrence and 1 with pelvic GIST). The median follow-up time was 9.5 months (range of 3-63). The median tumor sizes before and after initiation of IM treatment were 9.1 cm and 6.0 cm (p=0.003) based on the CT findings, respectively. All patients showed a decrease in tumor burden and the median tumor size reduction was 35%. Sixteen of the 18 patients showed a partial response to IM and two possessed stable disease. Nine of the 18 patients (50%) underwent surgical resection of primary or metastatic/recurrent tumors, with a median of 7 months of IM therapy. One case each of multivisceral resection and tumor recurrence were noted. CONCLUSIONS: IM as a preoperative therapy is feasible and safe for unresectable or metastatic/recurrent GIST that can effectively decrease tumor size, facilitating resection.

Preoperative imatinib for patients with primary unresectable or metastatic/recurrent gastrointestinal stromal tumor

OBJECTIVES: Despite its rising popularity, reports on the use of preoperative imatinib mesylate (IM) in patients with advanced gastrointestinal stromal tumor (GIST) are limited. This study aims to explore the clinical efficacy of preoperative IM in patients with primarily unresectable or metastatic/recurrent GIST. METHODS: Between September 2009 and February 2014, patients with primarily unresectable or metastatic/recurrent GIST treated by a single medical team were recruited and considered for preoperative IM therapy. Re-examination was conducted regularly and abdominal enhanced CT data, blood biochemistry and responses to IM were recorded. RESULTS: A total of 18 patients were enrolled, including 13 with a primary tumor (7 stomach, 3 small bowel, 2 rectal and 1 pelvic tumor) and 5 with recurrent or metastatic GIST (2 with liver metastasis, 2 with anastomotic recurrence and 1 with pelvic GIST). The median follow-up time was 9.5 months (range of 3-63). The median tumor sizes before and after initiation of IM treatment were 9.1 cm and 6.0 cm (p = 0.003) based on the CT findings, respectively. All patients showed a decrease in tumor burden and the median tumor size reduction was 35%. Sixteen of the 18 patients showed a partial response to IM and two possessed stable disease. Nine of the 18 patients (50%) underwent surgical resection of primary or metastatic/recurrent tumors, with a median of 7 months of IM therapy. One case each of multivisceral resection and tumor recurrence were noted. CONCLUSIONS: IM as a preoperative therapy is feasible and safe for unresectable or metastatic/recurrent GIST that can effectively decrease tumor size, facilitating resection. .

Protective effects of lycopene on oxidative stress, proliferation and autophagy in iron supplementation rats.

Lycopene is common in diet and known for its antioxidant activities. However, the impact of lycopene on iron metabolism is poorly investigated. In this study, we hypothesize that lycopene can prevent iron-mediated oxidative stress, proliferation and autophagy in liver and use a rat model of nutritional iron supplementation to confirm its intervention in these defence mechanisms. We found that iron supplementation induced cell proliferation predominantly in non parenchymal cells compared with hepatocytes, but not apoptosis. In addition, iron was accumulated within the hepatic lysosomes where it triggered autophagy as evidenced by the formation of autophagic vesicles detected by LC3-B staining. Iron supplementation also induced morphologic alterations of the mitochondrial membranes probably due to increased lipid peroxidation as indicated by elevated iron and malondialdehyde concentrations in serum and tissues. Lycopene reduced iron-catalyzed lipid peroxidation by decreasing the malondialdehyde level in the liver and colon and enhancing the total superoxide dismutase activities in serum and tissues. The result suggest that lycopene prevents iron-induced oxidative stress, proliferation and autophagy at both biochemical and histological levels due to its potent free radical scavenging and antioxidant properties.