To and fro in the archipelago: Repeated inter-island dispersal and New Guinea's orogeny affect diversification of Delias, the world's largest butterfly genus.

The world's largest butterfly genus Delias, commonly known as Jezebels, comprises ca. 251 species found throughout Asia, Australia, and Melanesia. Most species are endemic to islands in the Indo-Australian Archipelago or to New Guinea and nearby islands in Melanesia, and many species are restricted to montane habitats over 1200 m. We inferred an extensively sampled and well-supported molecular phylogeny of the group to better understand the spatial and temporal dimensions of its diversification. The remarkable diversity of Delias evolved in just ca. 15-16 Myr (crown age). The most recent common ancestor of a clade with most of the species dispersed out of New Guinea ca. 14 Mya, but at least six subsequently diverging lineages dispersed back to the island. Diversification was associated with frequent dispersal of lineages among the islands of the Indo-Australian Archipelago, and the divergence of sister taxa on a single landmass was rare and occurred only on the largest islands, most notably on New Guinea. We conclude that frequent inter-island dispersal during the Neogene-likely facilitated by frequent sea level change-sparked much diversification during that period. Many extant New Guinea lineages started diversifying 5 Mya, suggesting that orogeny facilitated their diversification. Our results largely agree with the most recently proposed species group classification system, and we use our large taxon sample to extend this system to all described species. Finally, we summarize recent insights to speculate how wing pattern evolution, mimicry, and sexual selection might also contribute to these butterflies' rapid speciation and diversification.

Arterial Spin Labeling: Techniques, Clinical Applications, and Interpretation.

Arterial spin labeling (ASL) is an emerging noninvasive MRI technique for assessing cerebral perfusion. An important advantage of ASL perfusion is the lack of a requirement for an exogenous tracer. ASL uses magnetically labeled water protons from arterial blood as an endogenous diffusible tracer. For this reason, ASL is an attractive perfusion imaging modality for children and for patients with contraindications or adverse reactions to gadolinium, patients with renal failure, and those who need repeated follow-up imaging. Another advantage of ASL is the possibility of quantifying cerebral blood flow, which provides an opportunity for comparative analysis among multiple longitudinal studies, unlike other MR perfusion techniques, which are semiquantitative and yield relative perfusion parameters. Advances in MRI technology and pulse sequence design have translated ASL beyond the research arena to successful clinical implementation. However, ASL is still underused in routine clinical practice. Some disadvantages of ASL include a lower signal-to-noise ratio and a longer acquisition time than those with dynamic susceptibility contrast-enhanced MRI. Additional factors limiting the use of ASL include variations in existing techniques and pulse sequence design, the complexity of implementation and postprocessing, insufficient experience with and/or knowledge of the potential clinical applications, and the absence of interpretation guidelines. The authors review the technical and physiologic basis of ASL perfusion, as well as artifacts, pitfalls, and its current clinical applications. A practical approach for interpreting ASL findings is also suggested.

An exploration of the complex biogeographical history of the Neotropical banner-wing damselflies (Odonata: Polythoridae).

BACKGROUND: The New World Tropics has experienced a dynamic landscape across evolutionary history and harbors a high diversity of flora and fauna. While there are some studies addressing diversification in Neotropical vertebrates and plants, there is still a lack of knowledge in arthropods. Here we examine temporal and spatial diversification patterns in the damselfly family Polythoridae, which comprises seven genera with a total of 58 species distributed across much of Central and South America. RESULTS: Our time-calibrated phylogeny for 48 species suggests that this family radiated during the late Eocene (~ 33 Ma), diversifying during the Miocene. As with other neotropical groups, the Most Recent Common Ancestor (MRCA) of most of the Polythoridae genera has a primary origin in the Northern Andes though the MRCA of at least one genus may have appeared in the Amazon Basin. Our molecular clock suggests correlations with some major geographical events, and our biogeographical modeling (with BioGeoBEARS and RASP) found a significant influence of the formation of the Pebas and Acre systems on the early diversification of these damselflies, though evidence for the influence of the rise of the different Andean ranges was mixed. Diversification rates have been uniform in all genera except one-Polythore-where a significant increase in the late Pliocene (~ 3 mya) may have been influenced by recent Andean uplift. CONCLUSION: The biogeographical models implemented here suggest that the Pebas and Acre Systems were significant geological events associated with the diversification of this damselfly family; while diversification in the tree shows some correlation with mountain building events, it is possible that other abiotic and biotic changes during our study period have influenced diversification as well. The high diversification rate observed in Polythore could be explained by the late uplift of the Northern Andes. However, it is possible that other intrinsic factors like sexual and natural selection acting on color patterns could be involved in the diversification of this genus.

Case 278: Mutation in ROBO3 Gene-Horizontal Gaze Palsy and Progressive Scoliosis.

HistoryA 13-year-old girl was born to consanguineous parents. She presented with mild intellectual impairment, convergent strabismus, horizontal gaze palsy, and bilateral abducens palsy. Vertical gaze was preserved, and no abnormalities suggesting facial paralysis were noted. In addition, she reported progressive back pain since she was 5 years old. Other symptoms were denied. No medications or related drugs had been administered thus far. The patient underwent brain MRI for further evaluation. Current and previous spine radiographs were also reviewed.

Case 278.

HistoryA 13-year-old girl was born to consanguineous parents. She presented with mild intellectual impairment, convergent strabismus, horizontal gaze palsy, and bilateral abducens palsy. Vertical gaze was preserved, and no abnormalities suggesting facial paralysis were noted. In addition, she reported progressive back pain since she was 5 years old. Other symptoms were denied. No medications or related drugs had been administered thus far.

Pediatric multiple sclerosis: from clinical basis to imaging spectrum and differential diagnosis.

Pediatric multiple sclerosis (MS) deserves special attention because of its impact on cognitive function and development. Although knowledge regarding pediatric MS has rapidly increased, understanding the peculiarities of this population remains crucial for disease management. There is limited expertise about the efficacy and safety of current disease-modifying agents. Although pathophysiology is not entirely understood, some risk factors and immunological features have been described and are discussed herein. While the revised International Pediatric MS Study Group diagnostic criteria have improved the accuracy of diagnosis, the recently revised McDonald criteria also offer some new insights into the pediatric population. It is fundamental that radiologists have strong knowledge about the vast spectrum of demyelinating disorders that can occur in childhood to ensure appropriate diagnosis and provide early treatment.

Tips and tricks in the diagnosis of intracranial dural arteriovenous fistulas: A pictorial review.

Dural arteriovenous fistulas (DAVFs) are complex vascular abnormalities that account for 10-15% of intracranial vascular malformations. DAVFs are typically encountered in middle-aged adults, with a slightly female predominance. The causative factors are still uncertain; however, abnormal local hemodynamics and neoangiogenesis related to dural sinus or venous thrombosis can contribute to DAVF occurrence. The diagnosis is dependent on a high level of clinical suspicion and high-resolution imaging techniques. Computed tomography and/or magnetic resonance imaging aid in the diagnosis, but conventional angiography remains the most accurate method for the complete characterization and classification of DAVFs. The therapeutic approach can be conservative or more aggressive, based on symptom severity, sequelae risk and patient characteristics. This article is a pictorial review of adult intracranial DAVFs that highlights some tips and tricks for recognizing useful red flags in the suspicion of DAVFs.

Integrating coalescent species delimitation with analysis of host specificity reveals extensive cryptic diversity despite minimal mitochondrial divergence in the malaria parasite genus Leucocytozoon.

BACKGROUND: Coalescent methods that use multi-locus sequence data are powerful tools for identifying putatively reproductively isolated lineages, though this approach has rarely been used for the study of microbial groups that are likely to harbor many unrecognized species. Among microbial symbionts, integrating genetic species delimitation methods with trait data that could indicate reproductive isolation, such as host specificity data, has rarely been used despite its potential to inform species limits. Here we test the ability of an integrative approach combining genetic and host specificity data to delimit species within the avian malaria parasite genus Leucocytozoon in central Alaska. RESULTS: We sequenced seven nuclear loci for 69 Leucocytozoon samples and used multiple species delimitation methods (GMYC and BPP models), tested for differences in host infection patterns among putative species based on 406 individual infections, and characterized parasite morphology. We found that cryptic morphology has masked a highly diverse Leucocytozoon assemblage, with most species delimitation methods recovering support for at least 21 separate species that occur sympatrically and have divergent host infection patterns. Reproductive isolation among putative species appears to have evolved despite low mtDNA divergence, and in one instance two Leucocytozoon cytb haplotypes that differed by a single base pair (~ 0.2% divergence) were supported as separate species. However, there was no consistent association between mtDNA divergence and species limits. Among cytb haplotypes that differed by one to three base pairs we observed idiosyncratic patterns of nuclear and ecological divergence, with cytb haplotype pairs found to be either conspecific, reproductively isolated with no divergence in host specificity, or reproductively isolated with divergent patterns of host specialization. CONCLUSION: Integrating multi-locus genetic species delimitation methods and non-traditional ecological data types such as host specificity provide a novel view of the diversity of avian malaria parasites that has been missed previously using morphology and mtDNA barcodes. Species delimitation methods show that Leucocytozoon is highly species-rich in Alaska, and the genus is likely to harbor extraordinary species-level diversity worldwide. Integrating genetic and ecological data will be an important approach for understanding the diversity and evolutionary history of microbial symbionts moving forward.

Neuromyelitis Optica Spectrum Disorders: Spectrum of MR Imaging Findings and Their Differential Diagnosis.

Neuromyelitis optica (NMO) is an autoimmune demyelinating disorder for which the aquaporin-4 (AQP4) water channels are the major target antigens. Advances in the understanding of NMO have clarified several points of its pathogenesis, clinical manifestations, and imaging patterns. A major advance was the discovery of the AQP4 antibody, which is highly specific for this disorder. Descriptions of new clinical and radiologic features in seropositive patients have expanded the spectrum of NMO, and the term NMO spectrum disorder (NMOSD) has been adopted. NMOSD is now included in a widening list of differential diagnoses. Acknowledgment of NMOSD imaging patterns and their mimicry of disorders has been crucial in supporting early NMOSD diagnosis, especially for unusual clinical manifestations of this demyelinating disease. This pictorial review summarizes the wide imaging spectrum of NMOSD and its differential diagnosis, as well as its historical evolution, pathophysiology, and clinical manifestations. ©RSNA, 2018.

Imaging of Creutzfeldt-Jakob Disease: Imaging Patterns and Their Differential Diagnosis.

Diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) remains a challenge because of the large variability of the clinical scenario, especially in its early stages, which may mimic several reversible or treatable disorders. The molecular basis of prion disease, as well as its brain propagation and the pathogenesis of the illness, have become better understood in recent decades. Several reports have listed recognizable clinical features and paraclinical tests to supplement the replicable diagnostic criteria in vivo. Nevertheless, we lack specific data about the differential diagnosis of CJD at imaging, mainly regarding those disorders evolving with similar clinical features (mimicking disorders). This review provides an update on the neuroimaging patterns of sCJD, emphasizing the relevance of magnetic resonance (MR) imaging, summarizing the clinical scenario and molecular basis of the disease, and highlighting clinical, genetic, and imaging correlations in different subtypes of prion diseases. A long list of differential diagnoses produces a comprehensive pictorial review, with the aim of enabling radiologists to identify typical and atypical patterns of sCJD. This review reinforces distinguishable imaging findings and confirms diffusion-weighted imaging (DWI) features as pivotal in the diagnostic workup of sCJD, as these findings enable radiologists to reliably recognize this rare but invariably lethal disease. A probable diagnosis is justified when expected MR imaging patterns are demonstrated and CJD-mimicking disorders are confidently ruled out. ©RSNA, 2017.

Signal intensity change on unenhanced T1-weighted images in dentate nucleus following gadobenate dimeglumine in patients with and without previous multiple administrations of gadodiamide.

OBJECTIVES: To evaluate the impact of previous administration of gadodiamide and neural tissue gadolinium deposition in patients who received gadobenate dimeglumine. METHODS: Our population included 62 patients who underwent at least three administrations of gadobenate dimeglumine, plus an additional contrast-enhanced last MRI for reference, divided into two groups: group 1, patients who in addition to gadobenate dimeglumine administrations had prior exposure to multiple doses of gadodiamide; group 2, patients without previous exposure to other gadolinium-based contrast agent (GBCAs). Quantitative analysis was performed on the first and last gadobenate dimeglumine MRIs in both groups. Dentate nucleus-to-middle cerebellar peduncle signal intensity ratios (DN/MCP) and relative change (RC) in signal over time were calculated and compared between groups using generalized additive model. RESULTS: Group 1 showed significant increase in baseline and follow-up DN/MCP compared to group 2 (p < 0.0001). The RC DN/MCP showed a non-statistically significant trend towards an increase in patients who underwent previous gadodiamide (p = 0.0735). CONCLUSION: There is increased T1 signal change over time in patients who underwent gadobenate dimeglumine and had received prior gadodiamide compared to those without known exposure to previous gadodiamide. A potentiating effect from prior gadodiamide on subsequent administered gadobenate dimeglumine may occur. KEY POINTS: • Neural gadolinium deposition is associated with multiple administrations of less stable GBCAs. • Less stable GBCA effect on subsequent more stable GBCA administrations is undetermined. • Significant increase of DN/MCP was seen in patients with previous gadodiamide exposure. • RC DN/MCP showed a non-significant increase in patients who received previous gadodiamide. • Potentiating effects from prior gadodiamide on subsequent administered gadobenate dimeglumine may occur.

High Signal Intensity in Globus Pallidus and Dentate Nucleus on Unenhanced T1-weighted MR Images: Evaluation of Two Linear Gadolinium-based Contrast Agents.

PURPOSE: To determine if a correlation exists between the number of previous enhanced magnetic resonance (MR) imaging examinations and high signal intensity in the globus pallidus (GP) and dentate nucleus (DN) in patients who received gadodiamide (Omniscan), a linear nonionic gadolinium-based contrast agent, and in those who received gadobenate dimeglumine (MultiHance), a linear ionic contrast agent. MATERIALS AND METHODS: Institutional review board approval was obtained for this single-center retrospective study, with waiver of informed consent. The study population included 69 patients divided into two groups: Group 1 included patients who underwent gadodiamide-enhanced MR imaging, and group 2 included patients who underwent gadobenate dimeglumine-enhanced MR imaging. Two radiologists conducted a quantitative analysis of unenhanced T1-weighted images by using region of interest measurements. The GP-to-thalamus (TH) signal intensity ratio, DN-to-middle cerebellar peduncle (MCP) signal intensity ratio and relative percentage change (Rchange) between the first and last examinations for each patient were calculated. Relation between the signal intensity ratios and Rchange and the number of enhanced MR imaging examinations was analyzed by using a generalized additive model. Inter- and intraobserver agreement was evaluated with the Lin concordance correlation coefficient test. RESULTS: Group 1 included 23 patients (19 female), with a mean of 5.0 doses ± 2.4 (standard deviation) (range, 3-11 doses) administered. Group 2 included 46 patients (24 female) with a mean of 4.6 doses ± 2.2 (range, 3-11 doses) administered. The interval between the first and last examination was 1500.1 days ± 780.2 (range, 98-3097 days) for group 1 and 1086.2 days ± 582.9 (range, 94-2633) for group 2. All patients had normal liver and renal function. Gadodiamide showed a significant increase in DN:MCP and GP:TH (P < .001 for both) and in Rchange (P = .001 for GP:TH, P < .001 for DN:MCP). In group 2, there was no significant increase in DN:MCP or GP:TH over time or in Rchange for GP:TH, but there was a significant trend toward an increase in Rchange for DN:MCP (P = .013). Interobserver agreement was almost perfect (0.99; 95% confidence interval: 0.99, 0.99) for all evaluated structures. Intraobserver agreement was substantial to almost perfect for both readers. CONCLUSION: A significant increase in GP:TH and DN:MCP is associated with multiple gadodiamide-enhanced studies but not with gadobenate dimeglumine-enhanced studies, likely reflecting differences in stability and elimination of both contrast agents. Rate-of-change data indirectly suggest gadolinium deposition in the DN with gadobenate dimeglumine use, although it is considerably less than that with gadodiamide use.

Magnetic resonance imaging of anterior temporal lobe cysts in children: discriminating special imaging features in a particular group of diseases.

INTRODUCTION: We hypothesised that disorders with anterior temporal lobe (ATL) cysts might exhibit common peculiarities and distinguishable imaging features that could be useful for diagnosis. We reviewed a series of patients for neuroimaging contributions to specific diagnoses. METHODS: A literature search was conducted, and institutional imaging files were reviewed to identify MR examinations with ATL cysts in children. Patients were divided according to head size, calcifications, white matter and cortical abnormalities. Unsupervised hierarchical clustering of patients on the basis of their MR and CT items was performed. RESULTS: We identified 23 patients in our database in whom MR revealed ATL cysts. Our series included five patients with congenital muscular dystrophy (05/23=21.7 %), six with megalencephalic leukoencephalopathy with subcortical cysts (06/23=26.1 %), three with non-megalencephalic leukoencephalopathy with subcortical cysts (03/23=13.1 %), seven with congenital cytomegalovirus disease (07/23=30.4 %) and two with Aicardi-Goutières syndrome (02/23=8.7 %). After analysis, 11 clusters resulted in the highest discriminative indices. Thereafter, patients' clusters were linked to their underlying diseases. The features that best discriminated between clusters included brainstem abnormalities, cerebral calcifications and some peculiar grey and white matter abnormalities. A flow chart was drafted to guide the radiologist in these diagnoses. CONCLUSIONS: The authors encourage the combined interpretation of these features in the herein proposed approach that confidently predicted the final diagnosis in this particular group of disorders associated with ATL cysts.

Objective Physical Activity Accumulation and Brain Volume in Older Adults: An MRI and Whole-Brain Volume Study.

A decrease in brain volume (ie, brain atrophy) is a marker of cognitive health in older adults. Insufficient weekly accumulation of moderate and vigorous physical activity (MVPA) has been associated with lower brain volume. As this association has been established for a small number of brain areas and structures and atrophy rates seem to be nonuniform between them, more comprehensive analyses are warranted. We compared the volume of 71 brain areas and structures in 45 older adults who met and did not meet objectively measured MVPA recommendations. In addition, we used multiple regression models to determine whether cardiorespiratory fitness (VO2PEAK), MVPA, and health-related risk factors could affect the atrophy of brain areas and structures. An accelerometer (GT9-X ActiGraph) was worn for 7 days. Participants were then classified into 2 groups: <150 minutes MVPA (<150'MVPA; n = 20) and ≥150 minutes MVPA (≥150'MVPA; n = 25) per week. Older adults who accumulated ≥150'MVPA per week had significantly higher absolute and relative (% of intracranial volume) volumes of 39 and 9 brain areas and structures, respectively, than those who accumulated <150'MVPA per week. Higher VO2PEAK seems to be a key predictor of the atrophy of brain areas and structures. In conclusion, meeting weekly physical activity recommendations seems to have a widespread effect on preserving the volume of more than 30 brain areas and structures in older adults. VO2PEAK seems to be the most frequent and important predictor of brain volume preservation.

Intracranial vessel wall magnetic resonance imaging features of infectious vasculitis.

Vasculitis is a complication of several infectious diseases affecting the central nervous system, which may result in ischemic and/or hemorrhagic stroke, transient ischemic attack, and aneurysm formation. The infectious agent may directly infect the endothelium, causing vasculitis, or indirectly affect the vessel wall through an immunological mechanism. The clinical manifestations of these complications usually overlap with those of non-infectious vascular diseases, making diagnosis challenging. Intracranial vessel wall magnetic resonance imaging (VWI) enables the evaluation of the vessel wall and the diseases that affect it, providing diagnostic data beyond luminal changes and enabling the identification of inflammatory changes in cerebral vasculitis. This technique demonstrates concentric vessel wall thickening and gadolinium enhancement, associated or not with adjacent brain parenchymal enhancement, in patients with vasculitis of any origin. It permits the detection of early alterations, even before a stenosis occurs. In this article, we review the intracranial vessel wall imaging features of infectious vasculitis of bacterial, viral, and fungal etiologies.

Modulation of Chitosan-TPP Nanoparticle Properties for Plasmid DNA Vaccines Delivery.

Nucleic acid vaccines have become a revolutionary technology to give a fast, safe, cost-effective and efficient response against viral infections, such as SARS-CoV-2 or Human papillomavirus (HPV). However, to ensure their effectiveness, the development of adequate methods to protect, carry, and deliver nucleic acids is fundamental. In this work, nanoparticles (NPs) of chitosan (CS)-tripolyphosphate (TPP)-plasmid DNA (pDNA) were thoroughly modulated and characterized, by measuring the charge and size through dynamic light scattering (DLS) and morphology by scanning electron microscopy (SEM). Stability, cytotoxicity and cellular uptake of NPs were also evaluated. Finally, the effect of polyplexes on the expression of HPV E7 antigen in human fibroblast and RAW cells was investigated through polymerase chain reaction (PCR) and real-time PCR. The results showed NPs with a spherical/oval shape, narrow size distribution <180 nm and positive zeta potentials (>20 mV) and good stability after one month of storage at 4 °C in formulation buffer or when incubated in culture medium and trypsin. In vitro studies of NPs cytotoxicity revealed that the elimination of formulation buffers led to an improvement in the rate of cell viability. The E7 antigen transcription was also increased for NPs obtained with high pDNA concentration (60 µg/mL). The analyzed CS-TPP-pDNA polyplexes can offer a promising vehicle for nucleic acid vaccines, not only in the prevention or treatment of viral infections, but also to fight emergent and future pathogens.

Design of Experiments to Achieve an Efficient Chitosan-Based DNA Vaccine Delivery System.

In current times, DNA vaccines are seen as a promising approach to treat and prevent diseases, such as virus infections and cancer. Aiming at the production of a functional and effective plasmid DNA (pDNA) delivery system, four chitosan polymers, differing in the molecular weight, were studied using the design of experiments (DoE) tool. These gene delivery systems were formulated by ionotropic gelation and exploring the chitosan and TPP concentrations as DoE inputs to maximize the nanoparticle positive charge and minimize their size and polydispersity index (PDI) as DoE outputs. The obtained linear and quadratic models were statistically significant (p-value < 0.05) and non-significant lack of fit, with suitable coefficient of determination and the respective optimal points successfully validated. Furthermore, morphology, stability and cytotoxicity assays were performed to evaluate the endurance of these systems over time and their further potential for future in vitro studies. The subsequent optimization process was successful achieved for the delivery systems based on the four chitosan polymers, in which the smallest particle size was obtained for the carrier containing the 5 kDa chitosan (~82 nm), while the nanosystem prepared with the high molecular weight (HMW) chitosan displayed the highest zeta potential (~+26.8 mV). Delivery systems were stable in the formulation buffer after a month and did not exhibit toxicity for the cells. In this sense, DoE revealed to be a powerful tool to explore and tailor the characteristics of chitosan/pDNA nanosystems significantly contributing to unraveling an optimum carrier for advancing the DNA vaccines delivery field.

Factors associated with prenatal care and seeking assistance in public hospitals in Vitória, Espírito Santo, Brazil.

Adequate prenatal care provides an opportunity for counseling and reducing the complications associated with pregnancy and delivery. Our objective was to describe the demographic, behavioral, and clinical profile of the pregnant women hospitalized at public maternity hospitals and to identify factors associated with six or more prenatal consultations in Vitória, Brazil. A cross-sectional study of 1,380 women was conducted in public maternity hospitals in Vitória, Brazil. Sixty-seven percent of participants had >or=6 prenatal consultations. Reasons for hospitalization were vaginal delivery (55.7%), cesarean section (32.9%), clinical treatment (7.7%), and abortion/miscarriage (3.7%). Having >or=9 years of schooling (odds ratio, OR = 1.8; 95% confidence interval, CI: 1.1-3.1), being married (OR = 1.9; 95% CI: 1.2-2.9) and delivering at term (OR = 3.6; 95% CI: 1.6-8.2) were significantly independently associated with having >or=6 prenatal consultations. Although higher education, being married, and delivering at term were associated with >or=6 prenatal consultations in this population, the high rate of Cesarean sections demonstrates the need for ongoing educative strategies among health professionals.