Differentially targeted seeding reveals unique pathological alpha-synuclein propagation patterns.

Parkinson's disease is a progressive neurodegenerative disorder characterized by the intracellular accumulation of insoluble alpha-synuclein aggregates into Lewy bodies and neurites. Increasing evidence indicates that Parkinson's disease progression results from the spread of pathologic alpha-synuclein through neuronal networks. However, the exact mechanisms underlying the propagation of abnormal proteins in the brain are only partially understood. The objective of this study was first to describe the long-term spatiotemporal distributions of Lewy-related pathology in mice injected with alpha-synuclein preformed fibrils and then to recreate these patterns using a computational model that simulates in silico the spread of pathologic alpha-synuclein. In this study, 87 2-3-month-old non-transgenic mice were injected with alpha-synuclein preformed fibrils to generate a comprehensive post-mortem dataset representing the long-term spatiotemporal distributions of hyperphosphorylated alpha-synuclein, an established marker of Lewy pathology, across the 426 regions of the Allen Mouse Brain Atlas. The mice were injected into either the caudoputamen, nucleus accumbens or hippocampus, and followed over 24 months with pathologic alpha-synuclein quantified at seven intermediate time points. The pathologic patterns observed at each time point in this high-resolution dataset were then compared to those generated using a Susceptible-Infected-Removed (SIR) computational model, an agent-based model that simulates the spread of pathologic alpha-synuclein for every brain region taking simultaneously into account the effect of regional brain connectivity and Snca gene expression. Our histopathological findings showed that differentially targeted seeding of pathological alpha-synuclein resulted in unique propagation patterns over 24 months and that most brain regions were permissive to pathology. We found that the SIR model recreated the observed distributions of pathology over 24 months for each injection site. Null models showed that both Snca gene expression and connectivity had a significant influence on model fit. In sum, our study demonstrates that the combination of normal alpha-synuclein concentration and brain connectomics contributes to making brain regions more vulnerable to the pathological process, providing support for a prion-like spread of pathologic alpha-synuclein. We propose that this rich dataset and the related computational model will help test new hypotheses regarding mechanisms that may alter the spread of pathologic alpha-synuclein in the brain.

Activation of sterol regulatory element-binding protein 1 (SREBP1)-mediated lipogenesis by the Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) promotes cell proliferation and progression of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. The EBV-encoded latent membrane protein 1 (LMP1), which is commonly expressed in NPC, engages multiple signaling pathways that promote cell growth, transformation, and metabolic reprogramming. Here, we report a novel function of LMP1 in promoting de novo lipogenesis. LMP1 increases the expression, maturation and activation of sterol regulatory element-binding protein 1 (SREBP1), a master regulator of lipogenesis, and its downstream target fatty acid synthase (FASN). LMP1 also induces de novo lipid synthesis and lipid droplet formation. In contrast, small interfering RNA (siRNA) knockdown of LMP1 in EBV-infected epithelial cells diminished SREBP1 activation and lipid biosynthesis. Furthermore, inhibition of the mammalian target of rapamycin (mTOR) pathway, through the use of either mTOR inhibitors or siRNAs, significantly reduced LMP1-mediated SREBP1 activity and lipogenesis, indicating that LMP1 activation of the mTOR pathway is required for SREBP1-mediated lipogenesis. In primary NPC tumors, FASN overexpression is common, with high levels correlating significantly with LMP1 expression. Moreover, elevated FASN expression was associated with aggressive disease and poor survival in NPC patients. Luteolin and fatostatin, two inhibitors of lipogenesis, suppressed lipogenesis and proliferation of nasopharyngeal epithelial cells, effects that were more profound in cells expressing LMP1. Luteolin and fatostatin also dramatically inhibited NPC tumor growth in vitro and in vivo. Our findings demonstrate that LMP1 activation of SREBP1-mediated lipogenesis promotes tumor cell growth and is involved in EBV-driven NPC pathogenesis. Our results also reveal the therapeutic potential of utilizing lipogenesis inhibitors in the treatment of locally advanced or metastatic NPC. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

EBV-encoded miRNAs target ATM-mediated response in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignancy that is prevalent in southern China and Southeast Asia. It is consistently associated with latent Epstein-Barr virus (EBV) infection. In NPC, miR-BARTs, the EBV-encoded miRNAs derived from BamH1-A rightward transcripts, are abundantly expressed and contribute to cancer development by targeting various cellular and viral genes. In this study, we establish a comprehensive transcriptional profile of EBV-encoded miRNAs in a panel of NPC patient-derived xenografts and an EBV-positive NPC cell line by small RNA sequencing. Among the 40 miR-BARTs, predominant expression of 22 miRNAs was consistently detected in these tumors. Among the abundantly expressed EBV-miRNAs, BART5-5p, BART7-3p, BART9-3p, and BART14-3p could negatively regulate the expression of a key DNA double-strand break (DSB) repair gene, ataxia telangiectasia mutated (ATM), by binding to multiple sites on its 3'-UTR. Notably, the expression of these four miR-BARTs represented more than 10% of all EBV-encoded miRNAs in tumor cells, while downregulation of ATM expression was commonly detected in all of our tested sequenced samples. In addition, downregulation of ATM was also observed in primary NPC tissues in both qRT-PCR (16 NP and 45 NPC cases) and immunohistochemical staining (35 NP and 46 NPC cases) analysis. Modulation of ATM expression by BART5-5p, BART7-3p, BART9-3p, and BART14-3p was demonstrated in the transient transfection assays. These findings suggest that EBV uses miRNA machinery as a key mechanism to control the ATM signaling pathway in NPC cells. By suppressing these endogenous miR-BARTs in EBV-positive NPC cells, we further demonstrated the novel function of miR-BARTs in inhibiting Zta-induced lytic reactivation. These findings imply that the four viral miRNAs work co-operatively to modulate ATM activity in response to DNA damage and to maintain viral latency, contributing to the tumorigenesis of NPC. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

The role of metabolic reprogramming in γ-herpesvirus-associated oncogenesis.

The γ-herpesviruses, EBV and KSHV, are closely associated with a number of human cancers. While the signal transduction pathways exploited by γ-herpesviruses to promote cell growth, survival and transformation have been reported, recent studies have uncovered the impact of γ-herpesvirus infection on host cell metabolism. Here, we review the mechanisms used by γ-herpesviruses to induce metabolic reprogramming in host cells, focusing on their ability to modulate the activity of metabolic regulators and manipulate metabolic pathways. While γ-herpesviruses alter metabolic phenotypes as a means to support viral infection and long-term persistence, this modulation can inadvertently contribute to cancer development. Strategies that target deregulated metabolic phenotypes induced by γ-herpesviruses provide new opportunities for therapeutic intervention.

Elevated Lactate Secondary to Gastrointestinal Beriberi.

Thiamine deficiency usually occurs with prolonged nutritional deficiency and is almost universally identified with Wernicke's encephalopathy or beriberi. It is also, however, a rare cause of elevated lactate and gastroenterological symptoms. This case report describes a 30-year-old man with 2 weeks of gastroenterological symptoms and intermittent oral intake, who was found to have an elevated lactate level. Neurological exam was normal and an extensive workup was negative, but after being treated with thiamine, his lactate level improved overnight and all of his symptoms resolved. Thiamine levels returned low at 44 nmol/L (normal 78-185 nmol/L). Lack of recognition of this phenomenon, while rare, can lead to unnecessary tests and procedures and increased morbidity and mortality.

Activation of the FGFR1 signalling pathway by the Epstein-Barr virus-encoded LMP1 promotes aerobic glycolysis and transformation of human nasopharyngeal epithelial cells.

Non-keratinizing nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. The EBV-encoded latent membrane protein 1 (LMP1) is believed to play an important role in NPC pathogenesis by virtue of its ability to activate multiple cell signalling pathways which collectively promote cell proliferation, transformation, angiogenesis, and invasiveness, as well as modulation of energy metabolism. In this study, we report that LMP1 increases cellular uptake of glucose and glutamine, enhances LDHA activity and lactate production, but reduces pyruvate kinase activity and pyruvate concentrations. LMP1 also increases the phosphorylation of PKM2, LDHA, and FGFR1, as well as the expression of PDHK1, FGFR1, c-Myc, and HIF-1α, regardless of oxygen availability. Collectively, these findings suggest that LMP1 promotes aerobic glycolysis. With respect to FGFR1 signalling, LMP1 not only increases FGFR1 expression, but also up-regulates FGF2, leading to constitutive activation of the FGFR1 signalling pathway. Furthermore, two inhibitors of FGFR1 (PD161570 and SU5402) attenuate LMP1-mediated aerobic glycolysis, cellular transformation (proliferation and anchorage-independent growth), cell migration, and invasion in nasopharyngeal epithelial cells, identifying FGFR1 signalling as a key pathway in LMP1-mediated growth transformation. Immunohistochemical staining revealed that high levels of phosphorylated FGFR1 are common in primary NPC specimens and that this correlated with the expression of LMP1. In addition, FGFR1 inhibitors suppress cell proliferation and anchorage-independent growth of NPC cells. Our current findings demonstrate that LMP1-mediated FGFR1 activation contributes to aerobic glycolysis and transformation of epithelial cells, thereby implicating FGF2/FGFR1 signalling activation in the EBV-driven pathogenesis of NPC.

Inhibition of the LKB1-AMPK pathway by the Epstein-Barr virus-encoded LMP1 promotes proliferation and transformation of human nasopharyngeal epithelial cells.

The association of Epstein-Barr virus (EBV) infection with the development of nasopharyngeal carcinoma (NPC) is well established. Latent membrane protein 1 (LMP1), the major oncogene encoded by EBV, is believed to play a crucial role in NPC pathogenesis by virtue of its ability to constitutively activate multiple cell signalling pathways. The LKB1-AMPK pathway is a master regulator of cellular metabolism that, via modulation of energy metabolism, has tumour suppressor activity. In this study we identify a novel ability of LMP1 to inhibit the LKB1-AMPK pathway through phosphorylation of LKB1 at serine 428 with subsequent suppression of the phosphorylation of AMPK and its substrates, ACC and Raptor. We show that MEK/ERK-MAPK signalling, activated by the CTAR1 domain of LMP1, is responsible for LKB1-AMPK inactivation. In addition, reactivation of AMPK signalling by AMPK activator, AICAR, abolished LMP1-induced cellular transformation (proliferation and anchorage-independent growth) in nasopharyngeal epithelial cells. Immunohistochemical staining revealed that a low level of phosphorylated AMPK is common in primary NPC specimens, and that this correlated significantly with the expression of LMP1. AICAR treatment inhibited the proliferation and anchorage-independent growth of NPC cells as well as potentiating the cytotoxic effect of the chemotherapeutic drug 5-fluorouracil. The current findings demonstrate that LMP1-mediated AMPK inactivation contributes to the proliferation and transformation of epithelial cells, thereby implicating the LKB1-AMPK pathway in the EBV-driven pathogenesis of NPC. Our findings also suggest that AMPK activators could be used to enhance the efficacy of conventional chemotherapeutic agents in the treatment of local and metastatic NPC.

Rare Autoinflammatory Neutrophilic Dermatoses in Pregnancy: Literature Review.

Rare cases of autoinflammatory neutrophilic dermatoses (AINDs) have been reported in patients during pregnancy with associated adverse maternal and fetal outcomes. Due to the rarity and heterogeneous morphology of pregnancy-associated AINDs, clinical diagnosis is often overlooked, and treatment options are limited. In this review, we present the epidemiology, clinical characteristics, therapeutic interventions, maternal and fetal outcomes, and discuss the possible pathophysiology of various pregnancy associated AINDs. Risk factors for the onset and exacerbation of AINDs in pregnancy include older maternal age, disease duration, and specific gestational age. The varied disease courses and conflicting clinical outcomes in both mothers and fetuses demonstrate the importance of symptom recognition and the understanding of the role of pregnancy on AINDs.

Exploration of Patient and Clinician Experience of Video Consultations in Community Palliative Care.

CONTEXT: Telehealth video consultations (VCs) were implemented in the community palliative care team (CPCT) in a regional NSW health district, Australia, as a response to restrictions to the COVID-19 pandemic, using patient's device in the absence of a clinician. OBJECTIVES: To evaluate patient/carer and clinician satisfaction in using VCs for CPC consultations; to explore advantages and challenges of VCs. METHODS: Self-reported online questionnaires to community-dwelling patients under care of the CPCT; seeking patients/carers and clinician perspectives on the VCs from April to September 2020. RESULTS: Of 126 eSurveys completed, (85 clinicians; 41 patients/carers), 97% patient/carers and 97% clinicians indicated they were satisfied with VC. Overall, 93% clinicians agreed they provided same level of care compared to face-to-face review; 85% patients/carers agreed they received same level of care compared to face-to-face consultations and 98% agreed their issues were addressed. Of eSurvey responses 97% clinicians and 78% patients/carers indicated they would continue to use VCs in practice. Comments indicated dissatisfaction with lack of personal examination; some found technological issues to be barriers. Benefits discovered incidentally were empowering patient independence to live out their end-of-life desires while being treated/supported, improved service delivery, increased staff autonomy and upskilling staff. CONCLUSION: Users in this study perceived VCs to have a place in CPC consultations. Using patient device enabled patient freedom, improved timeliness of clinical assessment, and communication to complement face-to-face consults, while minimizing infection risk. Unexpected, but valuable benefits were revealed. Workable technology is paramount.

Measuring Maxillary Posterior Tooth Movement: A Model Assessment using Palatal and Dental Superimposition.

Since the introduction of Invisalign by Align Technology, Inc. in 1999, questions and debates have persisted regarding the precision of Invisalign (clear aligner) therapy, particularly when compared to the use of traditional fixed appliances. This becomes particularly significant in cases involving anteroposterior, vertical, and transverse corrections, where precise comparisons are of paramount importance. To address these inquiries, this study introduces a meticulously devised protocol, placing a primary emphasis on digitally superimposing the movement of maxillary posterior teeth to facilitate accurate analysis. The sample included 25 patients who had completed their first series of Invisalign (clear) aligners. Four maxillary digital models (pre-treatment, post-treatment, ClinCheck-initial, and final models) were digitally superimposed using the palate rugae and dentitions as stable references. A software combination was used for model superimposition and tooth segmentation. Transformation matrices then expressed the differences between the achieved and predicted tooth positions. Thresholds for clinically relevant differences were at ±0.25 mm for linear displacement and ±2° for rotation. Differences were assessed using Hotelling's T-squared tests with Bonferroni correction. The mean differences in rotation (2.036° ± 4.217°) and torque (-2.913° ± 3.263°) were significant statistically and clinically, with p-values of 0.023 and 0.0003 respectively. De-rotation of premolars and torque control for all posterior teeth were less predictable. All mean differences for the linear measurements were statistically and clinically insignificant, except that the first molars seemed slightly (0.256 mm) more intruded than their predicted position. The clear aligner system appears to meet its prediction for most translational tooth movements and mesial-distal tipping in maxillary posterior teeth for non-extraction cases with mild to moderate malocclusions.

Clinical pharmacokinetics and pharmacodynamics of topical non-biological therapies for psoriasis patients.

INTRODUCTION: Psoriasis is a chronic inflammatory cutaneous disease that causes patients psychosocial distress. Topical therapies are utilized for mild-to-moderate disease and for more severe disease in conjunction with systemic therapies. Topical corticosteroids are a cornerstone of treatment for psoriasis, but long-term use can cause stria and cutaneous atrophy and as well as systemic side effects such as topical steroid withdrawal. Non-steroidal topical therapies tend to be safer than topical corticosteroids for long-term use. AREAS COVERED: We conducted a literature review on the pharmacokinetic (PK) and pharmacodynamic (PD) properties of topical therapies for psoriasis. We discuss how the PK and PD characteristics of these therapies inform clinicians on efficacy and toxicity when prescribing for patients. EXPERT OPINION: Topical corticosteroids, used intermittently, are very safe and effective. Long-term, continuous use of topical corticosteroids can cause systemic side effects. Several generic and newly approved non-steroidal options are available, but no head-to-head studies compare the effectiveness of the generics (vitamin D analogs, tacrolimus, pimecrolimus) against the newer therapies (roflumilast, tapinarof). Patients often do not respond to topical therapies due to poor adherence to treatment regimens. For patients resistant to topical treatment, phototherapy or systemic therapy may be an option.

Medical Students' Perceptions and Use of Formal and Informal Curriculum Resources.

Introduction  Resource overload describes the feeling medical students experience in choosing formal (faculty-prescribed) and informal study resources (not faculty-prescribed). This study aims to characterize students' use and perceptions of formal and informal study resources to inform their use in medical education. Methods  This is a mixed-methods study utilizing a convenience sample of first-year medical students enrolled at the University of Central Florida College of Medicine during the academic year 2020-2021. A 40-question, five-point Likert scale, survey based on Keller's Attention, Relevance, Confidence, and Satisfaction (ARCS) Model of Motivational Design was distributed to medical students during the end of their first year of medical school. Multivariate analysis of variance determined differences between formal and informal resources for each construct. Interviews were also conducted by first-year medical students and analyzed using thematic analysis. Learning logs were completed during the beginning of the medical students' second year to assess daily study habits. Results  Fifty-one students completed the survey with a response rate of 42.5%. Informal resources scored higher across all constructs: attention (formal: 3.4±1.2, informal: 4.0±1.1; p<.0125), relevance (formal: 3.8±1.1, informal: 4.3±1.0; p<.0125), confidence (formal: 3.2±1.2, informal: 4.1±1.1; p<.0125), satisfaction (formal: 2.8±1.2, informal: 3.6±1.2; p<.0125) (Likert scale 1-5, Mean±SD). Students found formal resources lacked depth and organization while informal resources allowed for concise understanding with retention cues. Learning log data reported similar use of formal and informal resources during week 1 (88.2% formal vs. 87.8% informal) and week 2 (84.6% formal vs. 82.6% informal). Conclusions  Students preferred informal resources based on ARCS constructs. However, the actual usage of formal and informal resources was similar. Formal resources align more with curricular assessments, but informal resources aid student retention and understanding. Therefore, students find both formal and informal resources necessary for success. Faculty should consider integrating informal curriculum resources to optimize student learning.

The pathological roles of BART miRNAs in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer prevalent in south-east Asia and southern China, where it constitutes a significant health burden. Although the close association of NPC with Epstein-Barr virus (EBV) infection has been known for more than four decades, the exact role that EBV plays in the pathogenesis of this malignancy is still unclear. While NPC tumours are known to express a number of EBV-encoded proteins, they also express a large number of virus-encoded microRNAs (miRNAs), the most abundant of which are those encoded from the BamHI-A region of the viral genome: the so-called BART miRNAs. miRNAs are small non-coding mRNAs that negatively regulate the expression of various genes at the post-transcriptional level. Accumulating evidence suggests that miRNAs play important roles in tumourigenesis. Here, we review the role of EBV-encoded BART miRNAs in modulating apoptosis and host innate defence mechanisms and their contribution to NPC pathogenesis. The rationale and strategies for therapeutic targeting of BART miRNAs in EBV-infected NPC are also discussed.

Novel 3D segmentation for reliable volumetric assessment of the nasal airway: a CBCT study.

OBJECTIVE: Nasal airway obstruction affects up to one-third of Americans and is one of the most common complaints by patients to otolaryngologists. Nasal airway obstruction and obstructive sleep apnea syndrome (OSAS) are closely related. The aim of this study was to use the 3D imaging software, ITK-SNAP as a platform to define a gold standard for anatomically accurate boundaries of the nasal airway in 3D CBCT and to create a more reliable and precise 3D CBCT segmentation of the nasal airway for assisting diagnosis, treatment, and monitoring of nasal airway obstruction and OSAS. METHOD AND MATERIALS: After review of the literature to identify established parameters using CBCT and CT technology for the segmentation of the nasal airway, and the existing drawbacks, a gold standard for locating the anatomical boundaries of the nasal airway using CBCT is proposed. This new method aims at standardization of segmentation and quantification, allowing for more reliable comparison between studies. ITK-SNAP software was used to segment three CBCT samples of healthy patients aged 21 to 59 years, who were patients of record, with CBCT obtained for either orthodontic, endodontic, or prosthodontic treatment planning purposes.
Results: The literature search identified 11 studies describing nasal airway parameters utilizing CBCT and CT. A great variation was detected on where the anatomical boundaries for the nasal airway were selected. A new standard in the identification of anatomical boundaries of the nasal airway is proposed for consistent segmentation and quantification using 3D CBCT by using the following landmarks: the inferior ANS-PNS border, the anterior nares border, the posterior sella-PNS border, and superiorly the border in alignment with the base of the skull (excluding the ostia, frontal, ethmoidal, and sphenoidal air cells). The three segmented samples were volumetrically measured, and statistically analyzed. The mean average Hounsfield unit intensity using the CBCT samples in this study was 629 with a standard deviation of 190.
Conclusion: The literature indicates a lack of a gold standard using CBCT technology for the segmentation of the nasal airway. With the proposed standard in this study, it is possible to quantify the nasal airway volume and thereby its reduction. For the general dental practitioner, this is an important aspect during the evaluation of overall airway assessment. This information can be useful in the diagnosis and treatment of airway compromised dental patients. (Quintessence Int 2021;52:154-164; doi: 10.3290/j.qi.a45429).

Evaluation of diagnostic radiology acumen between 2 groups of clinical dental students.

PURPOSE: To evaluate and distinguish if an additional year of clinical experience increases the cognitive ability of dental students to accurately assess and interpret dental radiographs. METHODS: Radiological acuity was assessed between two groups of clinical dental students at Penn Dental Medicine (PDM). Group 1 was composed of 147 third-year dental students (D3), group 2 was composed of 145 fourth-year dental students (D4). A 65-question test comprising the length and breadth of radiographic anatomy and pathology was administered to both D3 and D4 students. The test was designed to test the participants' knowledge of radiographic technique, anatomy, and differential diagnosis. The null hypothesis was that there would be no significant differences between the two groups. RESULTS: STATA 15 software (StataCorp LLC, College Station, TX, USA) was used to statistically analyze the findings. Although, the mean correct score for group 1 was higher (60/65) than group 2 (59/65), there was no statistically significant difference between the performance of the groups. On average, group 1 outperformed the clinically more experienced group 2 on an individual question basis. The average overall number of correctly answered items compared to incorrectly answered items reflected this difference. CONCLUSION(S): An additional year of clinical dental education does not appear to correlate with any higher radiographic acumen. This may be due to tapering exposure to unique pathology and findings, as more routine findings are encountered daily and classroom instruction during the fourth year of dental school is limited. Early incorporation of new radiographic education tools that are clinically oriented may be one method to increase retention of knowledge accumulated in the initial didactic years of dental education.

A Comparative Study of Social Impacts of the COVID-19 Pandemic on Republic of Korea, Japan, and Taiwan.

OBJECTIVE: The frequency of various disasters has become a 21st century global crisis. The biological-disaster of the coronavirus disease of 2019 (COVID-19) gave rise to a multi-dimensional global impact. The 25 items of Societal Influences Survey Questionnaire (SISQ) was developed to assess various categories of social influence during the pandemic. This study compares the SISQ scores of Taiwan, Republic of Korea (Korea) and Japan. METHODS: Persons living in Korea, Japan, and Taiwan were recruited and evaluated through an SISQ online survey. The SISQ is composed of 25 items each with a 4-point Likert scale. The SISQ assesses the following six factors: self-restraint, social impact, government policy, social cost, concern of infection, and awareness of information. A principal factor analysis and reliability (Cronbach's alpha) were performed to validate the SISQ. The analysis of variance (ANOVA) and post-hoc analysis was conducted to explore the differences between groups. RESULTS: The SISQ had acceptable reliabilities, and accounted for 58.86% of the variance. The significance for ANOVA with post-hoc analysis showed that scores of self-restraints ranked highest in Japan followed by Taiwan and Korea. Taiwanese scored lower than other nations regarding the concern of infection. Koreans scored higher in awareness of information than the other two nations. The effect of age and marital status were also estimated. CONCLUSION: The SISQ comprehensively evaluate multiple domains of social influence, and it manifests the divergence of social impacts across the three nations.

The Role of EBV-Encoded LMP1 in the NPC Tumor Microenvironment: From Function to Therapy.

Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. It is also characterized by heavy infiltration with non-malignant leucocytes. The EBV-encoded latent membrane protein 1 (LMP1) is believed to play an important role in NPC pathogenesis by virtue of its ability to activate multiple cell signaling pathways which collectively promote cell proliferation and survival, angiogenesis, invasiveness, and aerobic glycolysis. LMP1 also affects cell-cell interactions, antigen presentation, and cytokine and chemokine production. Here, we discuss how LMP1 modulates local immune responses that contribute to the establishment of the NPC tumor microenvironment. We also discuss strategies for targeting the LMP1 protein as a novel therapy for EBV-driven malignancies.

Development and validation of the Lo's Healthy and Happy Lifestyle Scale (LHHLS): The resilience in general population facing COVID-19 in Taiwan.

BACKGROUND: This article explores the effectiveness of development of the Lo's Healthy and Happy Lifestyle Scale (LHHLS), which is an evaluative tool that monitors the resilience of the Taiwan population in times of such COVID-19 epidemic. Also, to verify factors of resilience, namely the reliability and validity of self-efficacy and positive thinking, and establishment of a prospective norm analysis. METHOD: The study mainly applied Explorative Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) to develop LHHLS and establish the reliability and validity of the tool's structure, verify norm analysis and the reliability of data from each question using Cronbach's alpha. RESULTS: According to statistics, LHHLS has a good factorial effectiveness and relatively high reliability, with factor reliability analyses where Cronbach's alpha lies between 0.83 to 0.94. The 14 questions in the LHHLS has a total variance of 67.04%. The tool includes two sub-assessments that are theoretically and statistically appropriate: mental health/self-efficacy and positive thinking. CONCLUSION: The tool LHHLS can be applied to populations affected by COVID-19. With participants' self-awareness of mental health state and state of happy living, this tool is valid and reliable in assessing and evaluating the resilience of such participants against times of COVID-19. This study can become future use for epidemic prevention communities in monitoring residents' healthy living and changes in their resilience. Also, can become a reference standard for interventions to reduce the impacts populations' happy and healthy living, in times of biological disasters.