Comparative genomic and phylogenetic analysis of the first usutu virus isolate from a human patient presenting with neurological symptoms.

Usutu virus (USUV) is a mosquito-borne flavivirus, belonging to the Japanese encephalitis antigenic complex, that circulates among mosquitoes and birds. We describe and analyze the complete genome sequence of the first USUV strain isolated from an immunocompromised patient with neuroinvasive disease. This USUV isolate showed an overall nucleotide identity of 99% and 96%, respectively, with the genomes of isolates from Europe and Africa. Comparison of the human USUV complete polyprotein sequence with bird-derived strains, showed two unique amino acid substitutions. In particular, one substitution (S595G) was situated in the DIII domain of the viral Envelope protein that is recognized by flavivirus neutralizing antibodies. An additional amino acid substitution (D3425E) was identified in the RNA-dependent RNA polymerase (RdRp) domain of the NS5 protein. This substitution is remarkable since E3425 is highly conserved among the other USUV isolates that were not associated with human infection. However, a similar substitution was observed in Japanese encephalitis and in West Nile viruses isolated from humans. Phylogenetic analysis of the human USUV strain revealed a close relationship with an Italian strain isolated in 2009. Analysis of synonymous nucleotide substitutions (SNSs) among the different USUV genomes showed a specific evolutionary divergence among different countries. In addition, 15 SNSs were identified as unique in the human isolate. We also identified four specific nucleotide substitutions in the 59 and 39 untranslated regions (UTRs) in the human isolate that were not present in the other USUV sequences. Our analyses provide the basis for further experimental studies aimed at defining the effective role of these mutations in the USUV genome, their potential role in the development of viral variants pathogenic for humans and their evolution and dispersal out of Africa

Multiple right-sided pulmonary nodules: metastatic cancer or resectable early stage tumor?

The aim of this paper is to focus attention on complex cases of lung disease that may benefit from being managed outside formal guidelines. A 52 year-old man who had previously undergone a laryngectomy for squamous cell carcinoma, presented with a 1.2 cm nodule in the right upper pulmonary lobe. Three months later a new CT scan found that the nodule had slightly increased in size and also detected two new smaller nodules in the middle lobe. A PET/CT scan showed metabolic hyperactivity of all nodules. Since needle aspiration of the upper one revealed malignant cells, the patient was considered to be suffering from metastatic cancer and started on chemotherapy. At follow-up both CT and PET scans found a significant reduction in volume and activity of the lower nodules but no change in the upper one. At diagnostic thoracoscopy, histology demonstrated that the upper nodule was an adenocarcinoma while the lower ones were inflammatory. An upper lobectomy and systematic nodal dissection were therefore performed. Histology established a diagnosis of upper pulmonary adenocarcinoma and sarcoidosis. Our report suggests that in complicated oncologic cases in which non-invasive diagnostic tools yield incongruous results surgery should be considered without delay

GBR 12909 administration as a mouse model of bipolar disorder mania: mimicking quantitative assessment of manic behavior

Mania is a core feature of bipolar disorder (BD) that traditionally is assessed using rating scales. Studies using a new human behavioral pattern monitor (BPM) recently demonstrated that manic BD patients exhibit a specific profile of behavior that differs from schizophrenia and is characterized by increased motor activity, increased specific exploration, and perseverative locomotor patterns as assessed by spatial d. It was hypothesized that disrupting dopaminergic homeostasis by inhibiting dopamine transporter (DAT) function would produce a BD mania-like phenotype in mice as assessed by the mouse BPM. We compared the spontaneous locomotor and exploratory behavior of C57BL/6J mice treated with the catecholamine transporter inhibitor amphetamine or the selective DAT inhibitor GBR 12909 in the mouse BPM. We also assessed the duration of the effect of GBR 12909 by testing mice in the BPM for 3 h and its potential strain dependency by testing 129/SvJ mice. Amphetamine produced hyperactivity and increased perseverative patterns of locomotion as reflected in reduced spatial d values but reduced exploratory activity in contrast to the increased exploration observed in BD patients. GBR 12909 increased activity and reduced spatial d in combination with increased exploratory behavior, irrespective of inbred strain. These effects persisted for at least 3 h. Thus, selectively inhibiting the DAT produced a long-lasting cross-strain behavioral profile in mice that was consistent with that observed in manic BD patients. These findings support the use of selective DAT inhibition in animal models of the impaired dopaminergic homeostasis putatively involved in the pathophysiology of BD mania

Repeated Assessment of Exploration and Novelty Seeking in the Human Behavioral Pattern Monitor in Bipolar Disorder Patients and Healthy Individuals

Exploration and novelty seeking are cross-species adaptive behaviors that are dysregulated in bipolar disorder (BD) and are critical features of the illness. While these behaviors have been extensively quantified in animals, multivariate human paradigms of exploration are lacking. The human Behavioral Pattern Monitor (hBPM), a human version of the animal open field, identified a signature pattern of hyper-exploration in manic BD patients, but whether exploratory behavior changes with treatment is unknown. The objective of this study was to assess the sensitivity of the hBPM to changes in manic symptoms, a necessary step towards elucidating the neurobiology underlying BD.Twelve acutely hospitalized manic BD subjects and 21 healthy volunteers were tested in the hBPM over three sessions; all subjects were retested one week after their first session and two weeks after their second session. Motor activity, spatial and entropic (degree of unpredictability) patterns of exploration, and interactions with novel objects were quantified. Manic BD patients demonstrated greater motor activity, extensive and more unpredictable patterns of exploration, and more object interactions than healthy volunteers during all three sessions. Exploration and novelty-seeking slightly decreased in manic BD subjects over the three sessions as their symptoms responded to treatment, but never to the level of healthy volunteers. Among healthy volunteers, exploration did not significantly decrease over time, and hBPM measures were highly correlated between sessions.Manic BD patients showed a modest reduction in symptoms yet still demonstrated hyper-exploration and novelty seeking in the hBPM, suggesting that these illness features may be enduring characteristics of BD. Furthermore, behavior in the hBPM is not subject to marked habituation effects. The hBPM can be reliably used in a repeated-measures design to characterize exploration and novelty seeking and, in parallel with animal studies, can contribute to developing treatments that target neuropsychiatric disease

Hostility, Physical Aggression and Trait Anger as Predictors for Suicidal Behavior in Chinese Adolescents: A School-Based Study

Purpose: This study explored the extent to which trait aggression is associated with suicidal behavior in a nationwide school-based sample of adolescents. Methods: A nationwide sample of 14,537 high school students in urban areas of China was recruited. Information concerning suicide ideation, plans, attempts, trait aggression and other risk factors was collected by a self-reported questionnaire. Multivariate regression analyses were employed to predict suicidal behavior. Results: Approximately 18.5 % of students reported suicide ideation, 8.7 % reported suicide plans, and 4.1 % reported attempts during the past one year. Hostility and trait anger had a significant positive association with suicidal ideation. Hostility and physical aggression were positively related to suicide plans. Hostility had a positive correlation with suicide attempts, while trait anger was inversely associated with suicide attempts. Conclusions: This study suggests that hostility, physical aggression and trait anger may be able to be used to predict suicidal behavior among adolescents. Suicide prevention programs should target at attenuating the severity of hostility, anger and physical aggression. But teachers and parents should also give close attention to students with low trait anger

Management of Lung Nodules and Lung Cancer Screening During the COVID-19 Pandemic: CHEST Expert Panel Report

Background: The risks from potential exposure to coronavirus disease 2019 (COVID-19), and resource reallocation that has occurred to combat the pandemic, have altered the balance of benefits and harms that informed current (pre-COVID-19) guideline recommendations for lung cancer screening and lung nodule evaluation. Consensus statements were developed to guide clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic. / Methods: An expert panel of 24 members, including pulmonologists (n = 17), thoracic radiologists (n = 5), and thoracic surgeons (n = 2), was formed. The panel was provided with an overview of current evidence, summarized by recent guidelines related to lung cancer screening and lung nodule evaluation. The panel was convened by video teleconference to discuss and then vote on statements related to 12 common clinical scenarios. A predefined threshold of 70% of panel members voting agree or strongly agree was used to determine if there was a consensus for each statement. Items that may influence decisions were listed as notes to be considered for each scenario. / Results: Twelve statements related to baseline and annual lung cancer screening (n = 2), surveillance of a previously detected lung nodule (n = 5), evaluation of intermediate and high-risk lung nodules (n = 4), and management of clinical stage I non–small-cell lung cancer (n = 1) were developed and modified. All 12 statements were confirmed as consensus statements according to the voting results. The consensus statements provide guidance about situations in which it was believed to be appropriate to delay screening, defer surveillance imaging of lung nodules, and minimize nonurgent interventions during the evaluation of lung nodules and stage I non–small-cell lung cancer. / Conclusions: There was consensus that during the COVID-19 pandemic, it is appropriate to defer enrollment in lung cancer screening and modify the evaluation of lung nodules due to the added risks from potential exposure and the need for resource reallocation. There are multiple local, regional, and patient-related factors that should be considered when applying these statements to individual patient care

Comparison of (18)F SPECT with PET in myocardial imaging: A realistic thorax-cardiac phantom study

BACKGROUND: Positron emission tomography (PET) imaging with fluorine-18 ((18)F) Fluorodeoxyglucose (FDG) and flow tracer such as Rubidium-82 ((82)Rb) is an established method for evaluating an ischemic but viable myocardium. However, the high cost of PET imaging restricts its wider clinical use. Therefore, less expensive (18)F FDG single photon emission computed tomography (SPECT) imaging has been considered as an alternative to (18)F FDG PET imaging. The purpose of the work is to compare SPECT with PET in myocardial perfusion/viability imaging. METHODS: A nonuniform RH-2 thorax-heart phantom was used in the SPECT and PET acquisitions. Three inserts, 3 cm, 2 cm and 1 cm in diameter, were placed in the left ventricular (LV) wall to simulate infarcts. The phantom acquisition was performed sequentially with 7.4 MBq of (18)F and 22.2 MBq of Technetium-99m ((99m)Tc) in the SPECT study and with 7.4 MBq of (18)F and 370 MBq of (82)Rb in the PET study. SPECT and PET data were processed using standard reconstruction software provided by vendors. Circumferential profiles of the short-axis slices, the contrast and viability of the inserts were used to evaluate the SPECT and PET images. RESULTS: The contrast for 3 cm, 2 cm and 1 cm inserts were for (18)F PET data, 1.0 ± 0.01, 0.67 ± 0.02 and 0.25 ± 0.01, respectively. For (82)Rb PET data, the corresponding contrast values were 0.61 ± 0.02, 0.37 ± 0.02 and 0.19 ± 0.01, respectively. For (18)F SPECT the contrast values were, 0.31 ± 0.03 and 0.20 ± 0.05 for 3 cm and 2 cm inserts, respectively. For (99m)Tc SPECT the contrast values were, 0.63 ± 0.04 and 0.24 ± 0.05 for 3 cm and 2 cm inserts respectively. In SPECT, the 1 cm insert was not detectable. In the SPECT study, all three inserts were falsely diagnosed as "viable", while in the PET study, only the 1 cm insert was diagnosed falsely "viable". CONCLUSION: For smaller defects the (99m)Tc/(18)F SPECT imaging cannot entirely replace the more expensive (82)Rb/(18)F PET for myocardial perfusion/viability imaging, due to poorer image spatial resolution and poorer defect contrast

Is Lamarckian evolution relevant to medicine?

BACKGROUND: 200 years have now passed since Darwin was born and scientists around the world are celebrating this important anniversary of the birth of an evolutionary visionary. However, the theories of his colleague Lamarck are treated with considerably less acclaim. These theories centre on the tendency for complexity to increase in organisms over time and the direct transmission of phenotypic traits from parents to offspring. DISCUSSION: Lamarckian concepts, long thought of no relevance to modern evolutionary theory, are enjoying a quiet resurgence with the increasing complexity of epigenetic theories of inheritance. There is evidence that epigenetic alterations, including DNA methylation and histone modifications, are transmitted transgenerationally, thus providing a potential mechanism for environmental influences to be passed from parents to offspring: Lamarckian evolution. Furthermore, evidence is accumulating that epigenetics plays an important role in many common medical conditions. SUMMARY: Epigenetics allows the peaceful co-existence of Darwinian and Lamarckian evolution. Further efforts should be exerted on studying the mechanisms by which this occurs so that public health measures can be undertaken to reverse or prevent epigenetic changes important in disease susceptibility. Perhaps in 2059 we will be celebrating the anniversary of both Darwin and Lamarck

Interventional radiology virtual simulator for liver biopsy

Purpose Training in Interventional Radiology currently uses the apprenticeship model, where clinical and technical skills of invasive procedures are learnt during practice in patients. This apprenticeship training method is increasingly limited by regulatory restrictions on working hours, concerns over patient risk through trainees’ inexperience and the variable exposure to case mix and emergencies during training. To address this, we have developed a computer-based simulation of visceral needle puncture procedures. Methods A real-time framework has been built that includes: segmentation, physically based modelling, haptics rendering, pseudo-ultrasound generation and the concept of a physical mannequin. It is the result of a close collaboration between different universities, involving computer scientists, clinicians, clinical engineers and occupational psychologists. Results The technical implementation of the framework is a robust and real-time simulation environment combining a physical platform and an immersive computerized virtual environment. The face, content and construct validation have been previously assessed, showing the reliability and effectiveness of this framework, as well as its potential for teaching visceral needle puncture. Conclusion A simulator for ultrasound-guided liver biopsy has been developed. It includes functionalities and metrics extracted from cognitive task analysis. This framework can be useful during training, particularly given the known difficulties in gaining significant practice of core skills in patients