Short-Finned Pilot Whale Strandings Associated with Pilot Whale Morbillivirus, Brazil.

Cetacean morbillivirus (CeMV) causes illness and death in cetaceans worldwide; the CeMV strains circulating in the Southern Hemisphere are poorly known. We detected a pilot whale CeMV strain in 3 short-finned pilot whales (Globicephala macrorhynchus) stranded in Brazil during July-October 2020. Our results confirm this virus circulates in this species.

Peptidylprolyl isomerase C (Ppic) regulates invariant Natural Killer T cell (iNKT) differentiation in mice.

Peptidyl-prolyl cis-trans isomerase C (Ppic) is expressed in several bone marrow (BM) hematopoietic progenitors and in T-cell precursors. Since the expression profile of Ppic in the hematoimmune system was suggestive that it could play a role in hematopoiesis and/or T lymphocyte differentiation, we sought to test that hypothesis in vivo. Specifically, we generated a Ppic-deficient mouse model by targeting the endogenous locus by CRISPR/Cas9 and tested the requirement of Ppic in hematopoiesis. Several immune cell lineages covering BM progenitors, lymphocyte precursors, as well as mature cells at the periphery were analyzed. While most lineages were unaffected, invariant NKT (iNKT) cells were reduced in percentage and absolute cell numbers in the Ppic-deficient thymus. This affected the most mature stages in the thymus, S2 and S3, and the phenotype was maintained at the periphery. Additionally, immature transitional T1 and T2 B lymphocytes were increased in the Ppic-deficient spleen, but the phenotype was lost in mature B lymphocytes. In sum, our data show that Ppic is dispensable for myeloid cells, platelets, erythrocytes, αß, and γδ T lymphocytes in vivo in the steady state, while being involved in B- and iNKT cell differentiation.

Extraoral photobiomodulation for prevention of oral and oropharyngeal mucositis in head and neck cancer patients: interim analysis of a randomized, double-blind, clinical trial.

PURPOSE: To assess the safety and efficacy of prophylactic extraoral photobiomodulation (PBM) for the prevention of oral and oropharyngeal mucositis (OM) on clinical outcomes and survival in patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC). METHODS: OOPSCC patients who received radiotherapy (RT) were prospectively randomized to two groups: prophylactic extraoral PBM and placebo. OM grade (NCI), pain (VAS), analgesia, and anti-inflammatory prescriptions were assessed weekly. Quality of life questionnaires (QoL) were performed at the first and last day of RT. Following RT, participants were evaluated quarterly for oncological outcomes follow-up. RESULTS: Fifty-five patients met the inclusion criteria. The first occurrence of OM was observed at week 1, for the placebo group (p = 0.014). Later, OM onset and severity was observed for the PBM group, with first occurrence at week 2 (p = 0.009). No difference in severe OM incidence was observed (p > 0.05). Lower mean pain score was noted at week 7 for the PBM group (2.1) compared to placebo group (4.5) (p = 0.009). Less analgesics (week 3; p = 0.009/week 7; p = 0.02) and anti-inflammatory prescription (week 5; p = 0.0346) were observed for the PBM group. Better QoL scores were observed for the PBM group at last day of RT (p = 0.0034). No difference in overall survival among groups was observed in 1 year of follow-up (p = 0.889). CONCLUSION: Prophylactic extraoral PBM can delay OM onset, reduce pain, and reduce analgesic and anti-inflammatory prescription requirements. Extraoral PBM was associated with better QoL. There was no evidence of PBM impact on oncological outcomes. TRIAL REGISTRATION: TRN:RBR-4w4swx (date of registration: 01/20/2020).

COVID-19 impact on anxiety and depression in head and neck cancer patients: A cross-sectional study.

OBJECTIVE: To evaluate whether the coronavirus disease 2019 has increased anxiety, depression, and distress levels in head and neck cancer (HNC) patients undergoing radiotherapy (RT). METHODS: In this cross-sectional study, RT-HNC patients were surveyed using the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression and the distress thermometer (DT) for distress. HADS scores were compared with data pre-COVID-19. Additionally, we evaluated the COVID-19 impact on daily routines, treatment, and cancer care through a questionnaire. RESULTS: Fifty patients were included. The HADS mean score and estimated rates were 4.34 (±4.06)/22% for anxiety and 5.08 (±4.82)/22% for depression; in comparison, our historical control had 4.04 (±3.59)/20% for anxiety (p = .79) and 4.03 (±3.62)/17% for depression (p = .49). Mean DT score was 3.68 (±2.77). Responders were aware of COVID-19, afraid of having medical complications, believed it was life-threatening, did not miss appointments, believed their treatment was not impacted, and felt safe at the hospital amid the pandemic. CONCLUSION: This study suggests that anxiety, depression, and distress levels found in RT-HNC patients did not increase during the pandemic. Patients were afraid of being infected by COVID-19; however, they complied with their cancer treatment.

Cost-effectiveness of photobiomodulation therapy for the prevention and management of cancer treatment toxicities: a systematic review.

PURPOSE: To identify and summarize the evidence on the cost-effectiveness of photobiomodulation (PBM) therapy for the prevention and treatment of cancer treatment-related toxicities. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE). Scopus, MEDLINE/PubMed, and Embase were searched electronically. RESULTS: A total of 1490 studies were identified, and after a two-step review, 4 articles met the inclusion criteria. The included studies analyzed the cost-effectiveness of PBM therapy used in the context of lymphedema for breast cancer and oral mucositis (OM) induced by chemotherapy and radiotherapy. Better outcomes were associated with PBM therapy. The incremental cost-effectiveness ratio ranged from 3050.75 USD to 5592.10 USD per grade 3-4 OM case prevented. PBM therapy cost 21.47 USD per percentage point reduction in lymphedema in comparison with 80.51 USD for manual lymph drainage and physical therapy. CONCLUSION: There is limited evidence that PBM therapy is cost-effective in the prevention and treatment of specific cancer treatment-related toxicities, namely, OM and breast cancer-related lymphedema. Studies may have underreported the benefits due to a lack of a comprehensive cost evaluation. This suggests a wider acceptance of PBM therapy at cancer treatment centers, which has thus far been limited by the number of robust clinical studies that demonstrate cost-effectiveness for the prevention and treatment of toxicities.

Impact of pandemic COVID-19 outbreak on oral mucositis preventive and treatment protocols: new perspectives for extraoral photobiomodulation therapy.

This communication discusses the current challenges of oral mucositis (OM) management during the pandemic COVID-19 outbreak and reflects about an extraoral photobiomodulation protocol as an optimal alternative for preventing and treating OM in advanced cancer patients while minimizing the risk of infection by avoiding intraoral manipulation.

Is photobiomodulation therapy effective in reducing pain caused by toxicities related to head and neck cancer treatment? A systematic review.

Photobiomodulation therapy (PBMT) has been considered an effective method for preventing and managing certain cancer-related toxicities in head and neck cancer (HNC) patients treated with radiotherapy and chemotherapy. However, the potential effects of PBMT on pain control and analgesia resulting from these toxicities is still controversial. The aim of this systematic review was to compile available evidence of the effects of PMBT on pain control and reduced use of analgesics in HNC patients. We searched three indexed databases: MEDLINE/PubMed, Embase, and Scopus. The databases were reviewed up to and including December 2018. Only human clinical studies in English language were selected. Information was only available for mucositis and radiodermatitis. Fifteen out of 1112 studies met the inclusion criteria (14 for oral mucositis (OM) and 1 for radiodermatitis). From the 14 studies involving the prevention and treatment of OM, 10 had the study subjects compared to a placebo group. Of these 10 studies, all but 1 showed statistically significant difference related to pain control favoring the PBMT group. The study that compared PBMT with other treatment modality showed better results in pain control with PBMT. It appears that PBMT application frequency and potency impact on pain control. The only study involving the prevention and treatment of radiodermatitis was compared to placebo arm and showed statistically significant difference related to pain control favoring the PBMT group. Seven studies compared the need of analgesic medication between PBMT and placebo groups. Of these, five studies showed that the use of analgesic medication was significantly higher in the placebo group. The current evidence supports that PBMT is effective in pain control resulting from OM and radiodermatitis and may also reduce the need for analgesics. The evidence is not yet available of the effects of PBMT in other HNC treatment-related toxicities.

The retinal ganglion cell layer predicts normal-appearing white matter tract integrity in multiple sclerosis: A combined diffusion tensor imaging and optical coherence tomography approach.

We investigated the relationship between retinal layers and normal-appearing white matter (WM) integrity in the brain of patients with relapsing-remitting multiple sclerosis (MS), using a combined diffusion tensor imaging and high resolution optical coherence tomography approach. Fifty patients and 62 controls were recruited. The patients were divided into two groups according to presence (n = 18) or absence (n = 32) of optic neuritis. Diffusion tensor data were analyzed with a voxel-wise whole brain analysis of diffusion metrics in WM with tract-based spatial statistics. Thickness measurements were obtained for each individual retinal layer. Partial correlation and multivariate regression analyses were performed, assessing the association between individual retinal layers and diffusion metrics across all groups. Region-based analysis was performed, by focusing on tracts associated with the visual system. Receiver operating characteristic (ROC) curves were computed to compare the biomarker potential for the diagnosis of MS, using the thickness of each retinal layer and diffusion metrics. In patients without optic neuritis, both ganglion cell layer (GCL) and inner plexiform layer thickness correlated with the diffusion metrics within and outside the visual system. GCL thickness was a significant predictor of diffusion metrics in the whole WM skeleton, unlike other layers. No association was observed for either controls or patients with a history of optic neuritis. ROC analysis showed that the biomarker potential for the diagnosis of MS based on the GCL was high when compared to other layers. We conclude that GCL integrity is a predictor of whole-brain WM disruption in MS patients without optic neuritis.

The Effects of Benralizumab on Lung Volumes and Airway Resistance in Severe Eosinophilic Asthma: A Real-World Study.

INTRODUCTION: Add-on biological monoclonal antibodies such as benralizumab (anti-IL-5Ra) are recommended by international guidelines to reduce exacerbations in severe eosinophilic asthma (SEA). However, few studies have assessed the impact of these therapies on lung function-related outcomes. Our goal was to evaluate the effectiveness of benralizumab on lung function, including lung volumes and airway resistance, in SEA patients in Portugal. METHODS: This was a real-world, observational, prospective, multicentric study including adult patients diagnosed with SEA (January-June 2023). Spirometry and plethysmography were performed at baseline (T0) and after six months of treatment (T6) with benralizumab to assess: total lung capacity (TLC), residual volume (RV), forced expiratory volume in one second (FEV1), forced vital capacity (FVC), mean forced expiratory flow between 25% and 75% of FVC (mFEF-25/75), intrathoracic gas volume (ITGV), and respiratory airway resistance (Raw). Descriptive statistics (with categorical variables described as frequencies and continuous values as mean and standard deviation (SD)) and paired t-test and Cohen's d effect size were calculated (analyses performed in StataCorp v.15.1; StataCorp LLC, TX, USA). RESULTS: Overall, 30 SEA patients were evaluated, mostly women (n=18, 60.0%), with atopy (n=22, 73.3%), a mean age of 58.4 years (SD 11.7), and assisted by pulmonology (n=19, 63.3%) or immunology-allergology (n=11, 36.7%) services. Mean eosinophilia at baseline was 1103.57 cells/mcL (SD 604.88; minimum-maximum 460-2400); after the use of benralizumab, the count dropped to zero. After six months of treatment, a significant increase (p<0.0001) in FVC (15.3%), FEV1 (22.6%), and mFEF-25/75 (17.7%) were observed from baseline (Cohen's d between 0.78 and 1.11). ITGV, RV, RV/TLC, and Raw significantly decreased (p<0.0001) during the study period (-17.3%, -29.7%, -8.9%, and -100.6%, respectively) (Cohen's d between -0.79 and -1.06). No differences in TLC were obtained (p=0.173). No differences between sexes were observed for any measure. Patients with more significant eosinophilia (>900 cells/mcL count; n=15) presented better responses in FEV1 (p=0.001) and mFEF-25/75 (p=0.007). CONCLUSIONS: A notable eosinophil depletion with add-on benralizumab led to significant improvements in SEA patients' respiratory function (static lung volumes and airway resistance) in real-world settings after six months. The significant deflating effect of benralizumab on patients' hyperinflated lungs led to enhanced expiratory flow (increased FEV1 and mFEF-25/75) and air trapping (decreased RV/TLC), suggesting this antibody improves bronchial obstruction, lung hyperinflation, and airway resistance. Further studies in a larger population are required to confirm these findings.

Forced Expiratory Volume in One Second Quotient (FEV1Q) as a Prognostic Factor in Amyotrophic Lateral Sclerosis Patients: Comparing Its Predictive Value to Other Lung Function Measurements.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the first and second motor neurons. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) have conventionally served as indicators of respiratory muscle strength. Recently, FEV1Q (FEV1 divided by the sex-specific first percentile values of absolute FEV1 in adults with lung disease) has been suggested as a predictor of mortality. While FVC has been utilized as a prognostic factor, FEV1Q has not yet been examined. METHODS: This retrospective unicenter study evaluated FEV1Q as a predictor of mortality in ALS patients, comparing its predictive efficacy with other measurements, including FEV1, FVC, sniff nasal inspiratory pressure, and maximal inspiratory pressure. The study utilized univariate analysis for each variable employing the Cox proportional hazards model to determine the statistical significance and predictive power of each measurement. RESULTS: Forty-five patients were included, female predominant (60%) and an average age at diagnosis of 69.2 ± 11 years. Almost all (95%) met the criteria for non-invasive ventilation (NIV) and initiated (93%) during the study period, a mean of 137 days after diagnosis. The mortality rate observed was 57%, occurring at a median of 398 days post-diagnosis. On average, patients underwent 1.7 pulmonary function tests, revealing a decline in various parameters, including FEV1, FEV1Q, and FVC. However, only FEV1Q was a statistically significant predictor of mortality (p < 0.0083) in a Cox regression analysis. A negative coefficient for FEV1Q indicated that higher values were associated with a reduced mortality risk, with an average FEV1Q of 2.68 observed at the time of death. CONCLUSION: FEV1Q emerged as the only statistically significant predictor of mortality among the evaluated respiratory measurements in ALS patients. This study is the first to focus on applying FEV1Q in the clinical evaluation of ALS, marking an initial step in understanding its potential role in patient follow-up. However, further studies are needed before these findings can be incorporated into clinical practice.

Copaiba oil minimizes inflammation and promotes parenchyma re-epithelization in acute allergic asthma model induced by ovalbumin in BALB/c mice.

Introduction: Asthma is a condition of airflow limitation, common throughout the world, with high mortality rates, especially as it still faces some obstacles in its management. As it constitutes a public health challenge, this study aimed to investigate the effect of copaiba oil (e.g., Copaifera langsdorffii), as a treatment resource, at doses of 50 and 100 mg/kg on certain mediators of acute lung inflammation (IL-33, GATA3, FOXP3, STAT3, and TBET) and early mechanisms of lung remodeling (degradation of elastic fiber tissues, collagen deposition, and goblet cell hyperplasia). Methods: Using an ovalbumin-induced acute allergic asthma model in BALB/c mice, we analyzed the inflammatory mediators through immunohistochemistry and the mechanisms of lung remodeling through histopathology, employing orcein, Masson's trichrome, and periodic acid-Schiff staining. Results: Copaiba oil treatment (CO) reduced IL-33 and increased FOXP3 by stimulating the FOXP3/GATA3 and FOXP3/STAT3 pathways. Additionally, it upregulated TBET, suggesting an additional role in controlling GATA3 activity. In the respiratory epithelium, CO decreased the fragmentation of elastic fibers while increasing the deposition of collagen fibers, favoring epithelial restructuring. Simultaneously, CO reduced goblet cell hyperplasia. Discussion: Although additional research is warranted, the demonstrated anti-inflammatory and re-epithelializing action makes CO a viable option in exploring new treatments for acute allergic asthma.

Analysis of the correlation between climatic variables and Dengue cases in the city of Alagoinhas/BA.

The Aedes aegypti mosquito is the main vector of dengue and is a synanthropic insect and due to its anthropophilic nature, it has specific reproductive needs. In addition to that, it also needs tropical regions that provide climate-prone conditions that favor vector development. In this article, we propose the cross-correlation analysis between the climatic variables air temperature, relative humidity, weekly average precipitation and dengue cases in the period from 2017 to early 2021 in the municipality of Alagoinhas, Bahia, Brazil. To do so, we apply the trend-free cross-correlation, [Formula: see text], being a generalization of the fluctuation analysis without trend, where we calculate the cross correlation between time series to establish the influence of these variables on the occurrence of dengue disease. The results obtained here were a moderate correlation between relative humidity and the incidence of dengue cases, and a low correlation for relative air temperature and precipitation. However, the predominant factor in the incidence of dengue cases in the city of Alagoinhas is relative humidity and not air temperature and precipitation.

Combination of Iron and Zinc Enhanced the Root Cell Division, Mitotic Regularity and Nucleolar Activity of Hexaploid Triticale.

Hexaploid triticale results from crosses between durum wheat and rye. Despite its high agronomic potential, triticale is mainly used for livestock feed. Triticale surpasses their parental species in adaptability and tolerance to abiotic and biotic stresses, being able to grow in acidic soils where a high amount of iron (Fe) and zinc (Zn) is typical. On the other hand, high amounts of these essential trace elements can be cytotoxic to bread wheat. The cytotoxicity induced by seed priming with a high concentration of Fe and Zn impaired root cell division and induced nucleolar changes in bread wheat. Such cytogenetic approaches were expedited and successfully determined cytotoxic and suited micronutrient dosages for wheat nutripriming. With this study, we intended to analyse the hexaploid triticale cv 'Douro' root mitotic cell cycle and nucleolar activity after seed priming performed with aqueous solutions of iron (Fe) and/or zinc (Zn), containing a concentration that was previously considered cytotoxic, to bread wheat and to infer the higher tolerance of triticale to these treatments. The overall cytogenetic data allowed us to conclude that the Fe + Zn treatment enhanced the root mitotic index (MI), mitosis regularity and nucleolar activity of 'Douro' relative to the control and the individual treatments performed with Fe or Zn alone. The Fe + Zn treatment might suit triticale biofortification through seed priming.

Patient's perceptions of oral and oropharyngeal cancer diagnosis disclosure: communication aspects based on SPIKES protocol.

OBJECTIVE: Breaking bad medical news is a complex task of clinical practice. The manner in which this is done has a significant impact on patients. This study aimed to assess patient's perceptions regarding oral and oropharyngeal cancer diagnosis disclosure according to the "SPIKES" protocol. STUDY DESIGN: This cross-sectional study used a questionnaire with 21 SPIKES-based items. The questionnaire was administered to 100 patients with recently diagnosed oral and oropharyngeal squamous cell carcinoma who evaluated each item according to their preference and experience. RESULTS: Nineteen items showed a significant difference between patient's preference and recalled experience. Eighteen of these items showed lower experience scores primarily related to the amount of information desired by patients, presence of a companion, time to express feelings, and summary of information. Most patients preferred receiving as much information as possible about the diagnosis. However, only 35% reported that they had obtained sufficient information. Patients who were aware of cancer diagnostic suspicion had better communication experiences. CONCLUSIONS: Protocols may be useful to guide health professionals to support patient-centered strategies to disclose oral cancer diagnoses.

Therapeutic sequencing in the era of first-line immune checkpoint inhibitor combinations, a novel challenge in patients with metastatic clear-cell renal cell carcinoma.

Immune checkpoint inhibitor combinations have reshaped the treatment landscape of metastatic clear-cell renal cell carcinoma. As four regimens are now approved in the first-line setting, including nivolumab plus ipilimumab in intermediate and poor-risk patients, and pembrolizumab plus lenvatinib, nivolumab plus cabozantinib and pembrolizumab plus axitinib in all-comers, the choice of subsequent therapies is becoming a novel challenge for physicians. Such choices now rely on several compounds used as monotherapy which have demonstrated sustained activity after previous immune checkpoint or tyrosine kinase inhibitors. Future strategies may lie in novel targets, including hypoxia-inducible factor inhibitors, as well as further exploration of combinations in more advanced settings. Here we review the current evidence regarding treatment activity after immune checkpoint inhibitor combinations, the underlying biological and clinical challenges that may impact patient selection and the optimal sequencing strategies for clinical practice.

Damage-responsive neuro-glial clusters coordinate the recruitment of dormant neural stem cells in Drosophila.

Recruitment of stem cells is crucial for tissue repair. Although stem cell niches can provide important signals, little is known about mechanisms that coordinate the engagement of disseminated stem cells across an injured tissue. In Drosophila, adult brain lesions trigger local recruitment of scattered dormant neural stem cells suggesting a mechanism for creating a transient stem cell activation zone. Here, we find that injury triggers a coordinated response in neuro-glial clusters that promotes the spread of a neuron-derived stem cell factor via glial secretion of the lipocalin-like transporter Swim. Strikingly, swim is induced in a Hif1-α-dependent manner in response to brain hypoxia. Mammalian Swim (Lcn7) is also upregulated in glia of the mouse hippocampus upon brain injury. Our results identify a central role of neuro-glial clusters in promoting neural stem cell activation at a distance, suggesting a conserved function of the HIF1-α/Swim/Wnt module in connecting injury-sensing and regenerative outcomes.

Clinical and Laboratory Profile of People Living with HIV/AIDS with Oral Kaposi Sarcoma.

The aim of this article was to evaluate the clinical and laboratory profile of people with oral Kaposi's sarcoma (KS) associated with AIDS (KS-AIDS), followed-up at a public university hospital in Salvador, Bahia, Brazil, in the past 10 years. We identified patients diagnosed with KS-AIDS, presenting oral manifestation from January 2007 to December 2017. We searched, in the hospital information systems, the patient demographics, diagnostic data, treatment, image studies, and oral photographic records. Of the 39 cases of KS-AIDS identified at the institution, 14 (22.8%) presented oral lesions. There was a predominance of black men, with a mean age of 32.5 years. Most cases (85.1%) manifested signs of KS simultaneously with the diagnosis of HIV infection, with extremely low initial CD4 T cell counts (average of 52.6 cells/mm2) and visceral involvement (64.3%). The palate (32.1%) and gingiva (21.4%) were the most affected oral sites. Histologically, the tumors exhibited proliferation of spindle cells between vascular clefts and extravasated erythrocytes. Oral KS-AIDS was frequent in young black adult men, with severe immunosuppression and high viral load counting, mostly with lesions manifested in the same period of diagnosis of infection by the HIV.

Demographic, cardiological, microbiologic, and dental profiles of Brazilian patients who developed oral bacteria-related endocarditis.

OBJECTIVE: Infective endocarditis (IE) may cause devastating complications with high morbidity and mortality rates. The aim of the present study was to study the demographic, cardiological, microbiologic, and dental profiles of patients with oral bacteria-related IE. STUDY DESIGN: We present a retrospective study of patients with oral bacteria-related IE treated at Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de Sao Paulo, Brazil, between January 2009 and December 2019. RESULTS: Of the 100 patients included, 70% were male with a mean age of 45.4 years at diagnosis. The most affected sites were aortic and mitral valves, 60% in prosthetic heart valves, 34% in native valves, and 3% in pacemakers. The most common cause of valvular disease was rheumatic cardiopathy (51.9%), and the most frequent complications were valvular and perivalvular damage (26%). Streptococcus viridans was the most common species (96%), dental caries were present in 57% of the patients, 78% had tooth loss, 45% had apical periodontitis, and 77% were at high/moderate risk for periodontal disease. CONCLUSION: Oral bacteria-related IE among Brazilians was predominant in the prosthetic heart valves of young male adults previously affected by rheumatic cardiopathy. Streptococcus viridans was the main cause of IE, which was linked to patients with a poor oral health status.

Intracellular localization of hepatitis delta virus proteins in the presence and absence of viral RNA accumulation.

Hepatitis delta virus (HDV) encodes one protein, hepatitis delta antigen (deltaAg), a 195-amino-acid RNA binding protein essential for the accumulation of HDV RNA-directed RNA transcripts. It has been accepted that deltaAg localizes predominantly to the nucleolus in the absence of HDV genome replication while in the presence of replication, deltaAg facilitates HDV RNA transport to the nucleoplasm and helps redirect host RNA polymerase II (Pol II) to achieve transcription and accumulation of processed HDV RNA species. This study used immunostaining and confocal microscopy to evaluate factors controlling the localization of deltaAg in the presence and absence of replicating and nonreplicating HDV RNAs. When deltaAg was expressed in the absence of full-length HDV RNAs, it colocalized with nucleolin, a predominant nucleolar protein. With time, or more quickly after induced cell stress, there was a redistribution of both deltaAg and nucleolin to the nucleoplasm. Following expression of nonreplicating HDV RNAs, deltaAg moved to the nucleoplasm, but nucleolin was unchanged. When deltaAg was expressed along with replicating HDV RNA, it was found predominantly in the nucleoplasm along with Pol II. This localization was insensitive to inhibitors of HDV replication, suggesting that the majority of deltaAg in the nucleoplasm reflects ribonucleoprotein accumulation rather than ongoing transcription. An additional approach was to reevaluate several forms of deltaAg altered at specific locations considered to be essential for protein function. These studies provide evidence that deltaAg does not interact directly with either Pol II or nucleolin and that forms of deltaAg which support replication are also capable of prior nucleolar transit.