Slow-wave sleep and obstructive sleep apnea in patients with type 2 diabetes mellitus.

PURPOSE: This study aimed to analyze sleep architecture and obstructive sleep apnea (OSA) in patients with type 2 diabetes and clarify the association between sleep characteristics and glycemic control. METHODS: All participants underwent metabolism-related laboratory testing and a cross-sectional analysis of nocturnal polysomnography for sleep parameter analysis. Data were analyzed using the chi-squared test, a one-way analysis of variance, and Kruskal-Wallis test to compare the differences among three groups (type 2 diabetes, prediabetes, and control groups). The prevalence of OSA was evaluated using descriptive statistics and comparing the group divided into HbA1c quartiles. Univariate and multivariate linear regression analyses were used to determine factors associated with glycemic control. RESULTS: Of 75 study participants (age 57.3 ± 4.1 years, 32 men), there were 25 participants each in the type 2 diabetes, prediabetes, and control groups. Participants with type 2 diabetes had significantly decreased slow-wave sleep duration (77.9 ± 30.0 min, p = 0.026) and shortened rapid eye movement sleep latency (median 75 min, p = 0.018) compared with those in the prediabetes and control groups. Forty-five participants (60%) had OSA (apnea-hypopnea index ≥ 5/h), 18 of whom were in the type 2 diabetes group. The prevalence of OSA in this group was 72%. The prevalence of moderate-to-severe OSA was significantly higher in the type 2 diabetes group than in the control group (p = 0.025) and in groups with HbA1c levels of > 6.7% than in groups with HbA1c levels of < 5.3% (p = 0.007). Multiple regression analysis showed that dyslipidemia (ß = 0.179, p = 0.000) and slow-wave sleep duration (ß = - 0.113, p = 0.008) were independently associated with the HbA1c level. CONCLUSION: Our results suggest that increasing slow-wave sleep is positively associated with glycemic control.

Efficacy and Safety of Pregabalin for Muscle Cramps in Liver Cirrhosis: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Muscle cramp is possibly related to peripheral nerve hyperexcitability (PNH), and one of the most debilitating symptoms frequently encountered in patients with liver cirrhosis. We investigated whether pregabalin, a gamma-aminobutyric acid analogue, can suppress neuronal excitability and reduce muscle cramps in cirrhotic patients. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in which study participants with cirrhosis from a single tertiary center were enrolled. Primary endpoint was the relative change in cramp frequency from the run-in to standard dose treatment phase (4 weeks per each). Secondary endpoints included the responder rate, and the changes in cramp frequency during sleep, pain intensity, health-related quality of life (Liver Disease Quality of Life Instrument, Short Form-36) and electrophysiological measures of PNH. RESULTS: This study was terminated early because of insufficient accrual. 80% (n = 56) of the target number of participants (n = 70) were randomized to pregabalin (n = 29) or placebo (n = 27). Median baseline frequency of muscle cramps (interquartile range) was 5.8 (3.5-10) per week in the pregabalin group and 6.5 (4.0-10) in the placebo group (P = 0.970). The primary analysis showed a significant reduction in cramp frequency with pregabalin compared to placebo (-36% vs. 4.5% for the percentage change, P = 0.010). Secondary outcomes did not differ significantly between the two groups. Adverse effects with pregabalin were mainly dizziness and lethargy. CONCLUSION: With multiple problems emerging from premature termination in mind, the results suggested an acceptable safety profile and favorable effect of pregabalin in reducing muscle cramps compared to placebo in cirrhotic patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01271660.

Prophylactic endoscopic coagulation to prevent delayed post-EMR bleeding in the colorectum: a prospective randomized controlled trial (with videos).

BACKGROUND AND AIMS: Post-EMR bleeding (PEB) is the most common adverse event after EMR. However, there are no established endoscopic methods for the prevention of PEB. This study aimed to investigate whether prophylactic endoscopic coagulation (PEC) using coagulation probes reduces the incidence of overall delayed PEB. METHODS: We performed a randomized controlled study of patients undergoing EMR for large (≥10 mm) sessile lesions and laterally spreading tumors. Patients were randomized 1:1 to the EMR with coagulation group (n = 285) or EMR (control) group (n = 285). Immediate bleeding during colon EMR or clean-based ulcer after EMR was excluded. Clinically significant PEB was defined as bleeding requiring endoscopic hemostasis, hospitalization, or a decrease in the hemoglobin level >2 g/dL. RESULTS: A total of 569 patients were analyzed. The incidence of overall PEB was significantly lower in the EMR with coagulation group than in the control group (12.6% [36/285] vs 18.7% [53/284], P = .048). However, this was largely because of a reduction in minor bleeding. There was no difference in clinically significant PEB (1.8% [5/285] vs 3.2% [9/284], P = .276). Rectal location was a risk factor associated with overall PEB (odds ratio, 1.256; 95% confidence interval, 1.12-1.41; P < .001). CONCLUSIONS: Although this study found reduced PEB with prophylactic cautery of visible vessels, this was largely because of a reduction in minor bleeding with no benefit observed for clinically significant bleeding. Overall, PEB was more frequent with rectal lesions. (Clinical trial registration number: KCT0000779.).

Chronic relapsing inflammatory optic neuropathy (CRION): a manifestation of myelin oligodendrocyte glycoprotein antibodies.

BACKGROUND: Key clinical features of chronic relapsing inflammatory optic neuropathy (CRION) include relapsing inflammatory optic neuritis (ON) and steroid dependency, both of which have been reported among patients with myelin oligodendrocyte glycoprotein antibodies (MOG-Abs). We investigated the relevance of the presence of serum MOG-IgG with the current diagnostic criteria for CRION among patients with idiopathic inflammatory optic neuritis (iON). METHODS: Retrospective reviews of a database prospectively collated between 2011 and 2017 from the tertiary referral center for multiple sclerosis and neuromyelitis optica were performed. Sixty-four patients with iON, who did not meet the diagnostic criteria for multiple sclerosis, neuromyelitis optica (NMO) spectrum disorder with/without NMO-IgG, or acute disseminated encephalomyelitis and who had no symptomatic central nervous system (CNS) lesions other than on the optic nerve, were included from a cohort of 615 patients with inflammatory demyelinating diseases of the CNS. Fulfillment of the current diagnostic criteria for CRION, assay results for the serum IgG1 MOG-Ab, and characteristics of CRION patients with MOG-IgG were compared to those of non-CRION patients with MOG-IgG. RESULTS: Twelve iON patients fulfilled the current diagnostic criteria for CRION, 11 patients were positive for MOG-IgG, and one patient was borderline. Among the other 52 iON patients not meeting the criteria for CRION, 14 had relapsing disease courses and 38 had monophasic courses, of which MOG-IgG positivity were 0% and 29%, respectively. CRION patients with MOG-IgG had more relapsing disease courses (first steroid-dependent worsening/relapse in 2.3 months, range 0.4-7.0) and poorer optical coherence tomography outcomes at follow-up than non-CRION patients with MOG-IgG. However, patients in the two groups did not differ in terms of age of onset, sex, or steroid treatment duration after initial attack. CONCLUSIONS: CRION, according to the current diagnostic criteria, is a relapsing optic neuritis associated with MOG-IgG. Among iON patients with MOG-IgG, the absence of steroid-dependent attacks in the early stages of the disease may predict a long-term non-relapsing disease course and a more favorable outcome.

Neurotrophic Factor-α1: A Key Wnt-ß-Catenin Dependent Anti-Proliferation Factor and ERK-Sox9 Activated Inducer of Embryonic Neural Stem Cell Differentiation to Astrocytes in Neurodevelopment.

Embryonic neurodevelopment involves inhibition of proliferation of multipotent neural stem cells (NSCs) followed by differentiation into neurons, astrocytes and oligodendrocytes to form the brain. We have identified a new neurotrophic factor, NF-α1, which inhibits proliferation and promotes differentiation of NSC/progenitors derived from E13.5 mouse cortex. Inhibition of proliferation of these cells was mediated through negatively regulating the Wnt pathway and decreasing ß-catenin. NF-α1 induced differentiation of NSCs to astrocytes by enhancing Glial Fibrillary Acidic Protein (GFAP) expression through activating the ERK1/2-Sox9 signaling pathway. Cultured E13.5 cortical stem cells from NF-α1-knockout mice showed decreased astrocyte numbers compared to wild-type mice, which was rescued by treatment with NF-α1. In vivo, immunocytochemistry of brain sections and Western blot analysis of neocortex of mice showed a gradual increase of NF-α1 expression from E14.5 to P1 and a surge of GFAP expression at P1, the time of increase in astrogenesis. Importantly, NF-α1-Knockout mice showed ∼49% fewer GFAP positive astrocytes in the neocortex compared to WT mice at P1. Thus, NF-α1 is critical for regulating antiproliferation and cell fate determination, through differentiating embryonic stem cells to GFAP-positive astrocytes for normal neurodevelopment. Stem Cells 2017;35:557-571.

A Comparison of the Severe Cognitive Impairment Rating Scale With the Mini-Mental State Examination and Delirium Rating Scale-Revised-98 for Delirium: A Cross-sectional Study.

BACKGROUND: Cognitive impairment including attention deficits, disorientation, memory impairment, language disturbance, and impaired visuospatial ability are core symptoms of delirium. The Severe Cognitive Impairment Rating Scale (SCIRS) was developed to assess cognition in patients with severe dementia, but may also be useful in elderly people with delirium. OBJECTIVE: We investigated the use of the SCIRS to assess cognition in elderly patients with delirium. METHODS: We recruited 147 participants, aged ≥65 years, referred for psychiatric consultation at a tertiary-care university hospital. The diagnosis and severity of delirium were assessed using the Korean version of the Delirium Rating Scale-Revised-98 (K-DRS-98). Cognitive function was assessed using the SCIRS and the Mini-Mental State Examination (MMSE) in the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Assessment Packet (MMSE-KC). RESULTS: There was a strong correlation of SCIRS scores with K-DRS-98 cognition domain (r = -0.796), severity scores (r = -0.742), total scores (r = -0.734), and the MMSE-KC (r = 0.905). Analysis of variance incorporating the severity of delirium suggested that while the MMSE showed a floor effect, the SCIRS could discriminate between moderate and severe delirium. CONCLUSION: The SCIRS is a useful instrument to assess cognitive function in elderly patients with moderate to severe delirium.

Duration of Shh signaling contributes to mDA neuron diversity.

Sonic hedgehog (Shh) signaling is critical for various developmental processes including specification of the midbrain dopamine (mDA) neurons in the ventral mesencephalon (vMes). While the timing of Shh and its response gene Gli1 segregates mDA neurons, their overall lineage contribution to mDA neurons heavily overlaps. Here, we demonstrate that the same set of mDA neuron progenitors sequentially respond to Shh signaling (Gli1 expression), induce Shh expression, and then turn off Shh responsiveness. Thus, at any given developmental stage, cells rarely co-express Shh and Gli1. Using Shh(Cre:GFP) mice to delete the Smoothened receptor in the Shh pathway, we demonstrate that the loss of Shh signaling in Shh expressing cells results in a transient increase in proliferation and subsequent depletion of mDA neuron progenitors in the posterior vMes due to the facilitated cell cycle exit. Moreover, the change in duration of Shh signaling in vMes progenitors altered the timing of the contribution to the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc) mDA neurons. Taken together, our investigation on the relationship between the Shh-secreting and -responding cells revealed an intricate regulation of induction and cessation of Shh signaling that influences the distribution of mDA neurons in the VTA and SNc.

Depth-variant deconvolution of 3D widefield fluorescence microscopy using the penalized maximum likelihood estimation method.

We investigated the deconvolution of 3D widefield fluorescence microscopy using the penalized maximum likelihood estimation method and the depth-variant point spread function (DV-PSF). We build the DV-PSF by fitting a parameterized theoretical PSF model to an experimental microbead image. On the basis of the constructed DV-PSF, we restore the 3D widefield microscopy by minimizing an objective function consisting of a negative Poisson likelihood function and a total variation regularization function. In simulations and experiments, the proposed method showed better performance than existing methods.

Estimation of particle size distribution using photon autocorrelation function from dynamic light scattering considering unknown baseline.

Conventional methods for estimating particle size distribution (PSD) based on the computed field autocorrelation function (ACF) of dynamic light scattering data are prone to baseline error and random measurement errors. To reduce the effects of the errors efficiently and automatically, we propose a penalized nonlinear nonnegative least squares (NNLS) method based on the measured photon ACF that simultaneously determines the PSD and the unknown baseline. In simulations and experiments, the proposed method was able to estimate the PSD more accurately than the existing NNLS method using the computed field ACF.

Shh pathway activation is present and required within the vertebrate limb bud apical ectodermal ridge for normal autopod patterning.

Expression of Sonic Hedgehog (Shh) in the posterior mesenchyme of the developing limb bud regulates patterning and growth of the developing limb by activation of the Hedgehog (Hh) signaling pathway. Through the analysis of Shh and Hh signaling target genes, it has been shown that activation in the limb bud mesoderm is required for normal limb development to occur. In contrast, it has been stated that Hh signaling in the limb bud ectoderm cannot occur because components of the Hh signaling pathway and Hh target genes have not been found in this tissue. However, recent array-based data identified both the components necessary to activate the Hh signaling pathway and targets of this pathway in the limb bud ectoderm. Using immunohistochemistry and various methods of detection for targets of Hh signaling, we found that SHH protein and targets of Hh signaling are present in the limb bud ectoderm including the apex of the bud. To directly test whether ectodermal Hh signaling was required for normal limb patterning, we removed Smo, an essential component of the Hh signaling pathway, from the apical ectodermal ridge (AER). Loss of functional Hh signaling in the AER resulted in disruption of the normal digit pattern and formation of additional postaxial cartilaginous condensations. These data indicate that contrary to previous accounts, the Hh signaling pathway is present and required in the developing limb AER for normal autopod development.

Primary Production in the Kara, Laptev, and East Siberian Seas.

Understanding of the primary production of phytoplankton in the Kara Sea (KS), the Laptev Sea (LS), and the East Siberian Sea (ESS) remains limited, despite the recognized importance of phytoplankton in the Arctic Ocean. To address this knowledge gap, we conducted three NABOS (Nansen and Amundsen Basins Observational System) expeditions in 2013, 2015, and 2018 to measure in situ primary production rates using a 13C-15N dual-tracer method and examine their major controlling factors. The main goals in this study were to investigate regional heterogeneity in primary production and derive its contemporary ranges in the KS, LS, and ESS. The daily primary production rates in this study (99 ± 62, 100 ± 77, and 56 ± 35 mg C m-2 d-1 in the KS, LS, and ESS, respectively) are rather different from the values previously reported in each sea mainly because of spatial and regional differences. Among the three seas, a significantly lower primary production rate was observed in the ESS in comparison to those in the KS and LS. This is likely mainly because of regional differences in freshwater content based on the noticeable relationship (Spearman, rs = -0.714, p < 0.05) between the freshwater content and the primary production rates observed in this study. The contemporary ranges of the annual primary production based on this and previous studies are 0.96-2.64, 0.72-50.52, and 1.68-16.68 g C m-2 in the KS, LS, and ESS, respectively. Further intensive field measurements are warranted to enhance our understanding of marine microorganisms and their community-level responses to the currently changing environmental conditions in these poorly studied regions of the Arctic Ocean.

Using a Deep Learning Model to Address Interobserver Variability in the Evaluation of Ulcerative Colitis (UC) Severity.

The use of endoscopic images for the accurate assessment of ulcerative colitis (UC) severity is crucial to determining appropriate treatment. However, experts may interpret these images differently, leading to inconsistent diagnoses. This study aims to address the issue by introducing a standardization method based on deep learning. We collected 254 rectal endoscopic images from 115 patients with UC, and five experts in endoscopic image interpretation assigned classification labels based on the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scoring system. Interobserver variance analysis of the five experts yielded an intraclass correlation coefficient of 0.8431 for UCEIS scores and a kappa coefficient of 0.4916 when the UCEIS scores were transformed into UC severity measures. To establish a consensus, we created a model that considered only the images and labels on which more than half of the experts agreed. This consensus model achieved an accuracy of 0.94 when tested with 50 images. Compared with models trained from individual expert labels, the consensus model demonstrated the most reliable prediction results.

Gli3 is required for maintenance and fate specification of cortical progenitors.

Gli3, one of three vertebrate Gli transcription factors in Hedgehog (Hh) pathway, is processed into a repressor form (Gli3R) in the absence of Hh signal and acts as the major negative transducer of the pathway. Although the role of Gli3 in embryonic patterning has been extensively studied, its role in cortical neurogenesis, especially in the regulation of neural progenitors in proliferation and cell fate specification, is largely unknown. To bypass the patterning defects caused by loss of Gli3, we conditionally deleted Gli3 after patterning was complete in mouse. Our results from birthdating and in utero electroporation experiments demonstrate that the Gli3, specifically Gli3R, is critical for specifying the fate of cortical neurons that are generated following a stereotypical temporal order. Moreover, Gli3 is required for maintaining the cortical progenitors in active cell cycle, suggesting that cells may acquire differentiated status as they turn off Gli3 expression during neurogenesis.

Usefulness of Semi-cylindrical Beam Spoiler in Treatment of Early Glottic Cancer Using 6 MV Photon Beam.

BACKGROUND/AIM: To assess the dosimetric influence of a semi-cylindrical beam spoiler (sCBS) for the treatment of early glottic cancer using a 6 MV photon beam. PATIENTS AND METHODS: The 2D dose distributions were also calculated and measured with and without the sCBS and with a 0.5 cm thick bolus. A retrospective study of 8 patients treated between 2012 and 2018 was performed. RESULTS: The 2D dose distributions obtained from the treatment planning system (TPS) and film measurements were in good agreement. In the planning study, the V95%, V100%, conformal index (CI), and homogeneity index (HI) of all pPTVs for the sCBS plans were better than those for the open field plans (p<0.01). Especially, sCBS plans had better skin sparing effect than bolus plans (p<0.05). CONCLUSION: The sCBS of the 6 MV photon beam could be a useful tool for the treatment of early glottic cancers.

Associations of health-related quality of life with depression and stigma in MERS-CoV survivors during the recovery period.

ABSTRACT: We explored factors related to health-related quality of life (HRQOL), including psychiatric symptoms and stigma related to Middle East respiratory syndrome coronavirus (MERS-CoV) infection, among MERS-CoV survivors during the recovery period.Sixty-three MERS-COV survivors were recruited from five hospitals for a cohort study, one year after their infection in 2015. The subjects' demographic information and medical conditions associated with MERS-CoV were recorded. HRQOL was evaluated using the Short Form-8 Health Survey (SF-8). Depression, post-traumatic stress symptoms, chronic fatigue, and perceived stigma were assessed using several questionnairesThe mean physical component summary (PCS) and mean mental component summary (MCS) of the SF-8 score were below 50 T (43.47 ±â€Š9.60, 45.74 ±â€Š10.18). Depression, chronic fatigue, posttraumatic stress symptoms and stigma were negatively correlated with the SF-8 PCS and MCS. Multivariate logistic regression analysis showed that the PCS was associated with stigma (OR 8.66, 95% CI 1.96-38.23), whereas MCS was associated with depression (OR 26.62, 95% CI 3.56-198.85).The estimated HRQOL of MERS-CoV survivors during recovery was poor and appeared to be associated with depression and MERS-related stigma.

In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog.

Sonic hedgehog (Shh) has been implicated in the ongoing neurogenesis in postnatal rodent brains. Here we adopted an in vivo genetic fate-mapping strategy, using Gli1 (GLI-Kruppel family member) as a sensitive readout of Shh activity, to systematically mark and follow the fate of Shh-responding cells in the adult mouse forebrain. We show that initially, only a small population of cells (including both quiescent neural stem cells and transit-amplifying cells) responds to Shh in regions undergoing neurogenesis. This population subsequently expands markedly to continuously provide new neurons in the forebrain. Our study of the behaviour of quiescent neural stem cells provides in vivo evidence that they can self-renew for over a year and generate multiple cell types. Furthermore, we show that the neural stem cell niches in the subventricular zone and dentate gyrus are established sequentially and not until late embryonic stages.

Customized 3D Bolus Applied to the Oral Cavity and Supraclavicular Area for Head and Neck Cancer.

BACKGROUND/AIM: In this study, a new method to create a customized three-dimensional (3D) bolus by accurately considering the anatomy of an individual patient is demonstrated. PATIENTS AND METHODS: A 3D bolus structure was created from an extended planning target volume (PTV) to reduce an inevitable skin reaction. In addition, during computed tomography simulation in patients with oral cavity cancers, a balloon was inserted into the mouth of a patient to secure space, and then the area surrounding the balloon was designed into a 3D bolus structure. RESULTS: For patients with head and neck cancers, a customized 3D bolus can reduce the unnecessary skin dose by 14.4% compared to a commercial bolus. For patients with oral cavity cancer, the PTV and tongue doses were 93.8% and 8% of the prescribed dose, respectively. CONCLUSION: The customized 3D bolus enables effective skin sparing and full coverage of the target area.

Perceptions and Feasibility of Actions Related to Sodium Reduction among Restaurant Owners and Cooks in Seongnam, South Korea: Comparison According to Stages of Behavioral Change.

With the increase in meals eaten outside the home, sodium reduction in restaurant foods is essential for reducing sodium intake. This study aimed to assess the stages of behavioral change for reducing sodium and the differences in perceptions among restaurant staff by stage. Restaurant owners and cooks (n = 313) in Seongnam, South Korea were surveyed on their stage of behavioral change, practices, and perceptive factors related to sodium reduction in restaurant meals using a questionnaire. The proportion of behavioral change by stage was 20.4% in the maintenance and action (MA) stage, 32.3% in the preparation (P) stage, and 47.3% in the pre-preparation (PP) stage, which included contemplation and pre-contemplation stages. The items that represent differences among the groups were recognition of social environment for sodium reduction, practice of weighing condiments and measuring salinity, and feasibility of actions related to low-sodium cooking. Logistic regression analysis was used to estimate odds ratios for practice and perceptive factors by using stage of behavioral change as the independent variable. Factors associated with being in the MA stage were weighing condiments, measuring salinity, and high feasibility of actions related to low-sodium cooking. Recognition of sodium labeling and anticipation of better taste by reducing sodium increased the odds of being in the P stage rather than the PP stage. These results suggest that customized stepwise education and support are needed for the efficacy of restaurant-based sodium reduction programs.

Content Analysis of Korean Videos Regarding Restless Legs Syndrome on YouTube.

OBJECTIVE: To evaluate the accuracy and quality of Korean videos associated with restless legs syndrome (RLS) on YouTube. METHODS: A YouTube search was performed on April 1, 2020 using the term "restless legs syndrome" in the Korean language. Two reviewers coded the source, content, and demographics of the included videos. Video quality was assessed using the modified DISCERN (mDISCERN) instrument. RESULTS: Among the 80 videos analyzed, 44 (55.0%) were reliable, and 36 (45.0%) were misleading. There was a trend toward a higher number of mean daily views in the misleading videos than in the reliable videos. Most of the misleading videos (72.2%) advocated complementary and alternative medicine as a primary treatment for RLS. Although the reliable videos had higher mDISCERN scores than the misleading videos, the overall quality of the reliable videos was low. CONCLUSION: Many Korean videos regarding RLS on YouTube involve a risk of exposure to misinformation and are of unsatisfactory quality.

Inhibition of endocytosis of porcine reproductive and respiratory syndrome virus by rottlerin and its potential prophylactic administration in piglets.

Owing to several limitations of porcine reproductive and respiratory syndrome virus (PRRSV) control procedures, the importance of antiviral agents is increasing; however, limited studies have been done on the development of anti-PRRSV agents. Herein, we explored the antiviral effect and mechanism of rottlerin against PRRSV. We demonstrated that treatment of rottlerin at an early stage of PRRSV infection significantly inhibited the viral replication. PRRSV infection induced protein kinase C-δ phosphorylation, which was specifically downregulated by rottlerin. The treatment of rottlerin led to disrupting the PRRSV entry pathway by blocking endocytosis of the virions. Further, to evaluate the anti-PRRSV effect of the rottlerin in vivo, we administrated rottlerin loaded liposome to pigs infected with PRRSV LMY or FL12 strain. The treatment of rottlerin-liposome reduced the blood viral load, interstitial pneumonia and clinical scores compared to untreated pigs. These results provide an evidence of anti-PRRSV effect of rottlerin in vitro via inhibiting PRRSV internalization and in vivo, all of which strongly suggest the applicability of rottlerin as a potential PRRSV prophylactic treatment.