Ganglionic eminence: volumetric assessment of transient brain structure utilizing fetal magnetic resonance imaging.

OBJECTIVE: To provide quantitative magnetic resonance imaging (MRI) super-resolution-based three-dimensional volumetric reference data on the growth dynamics of the ganglionic eminence (GE) relative to cortical and total fetal brain volumes (TBV). METHODS: This was a retrospective study of fetuses without structural central nervous system anomalies or other confounding comorbidities that were referred for fetal MRI. Super-resolution reconstructions of 1.5- and 3-Tesla T2-weighted images were generated. Semiautomatic segmentation of TBV and cortical volume and manual segmentation of the GE were performed. Cortical volume, TBV and GE volume were quantified and three-dimensional reconstructions were generated to visualize the developmental dynamics of the GE. RESULTS: Overall, 120 fetuses that underwent 127 MRI scans at a mean gestational age of 27.23 ± 4.81 weeks (range, 20-37 weeks) were included. In the investigated gestational-age range, GE volume ranged from 74.88 to 808.75 mm3 and was at its maximum at 21 gestational weeks, followed by a linear decrease (R2 = 0.559) throughout the late second and third trimesters. A pronounced reduction in GE volume relative to cortical volume and TBV occurred in the late second trimester, with a decline in this reduction observed in the third trimester (R2 = 0.936 and 0.924, respectively). Three-dimensional rendering allowed visualization of a continuous change in the shape and size of the GE throughout the second and third trimesters. CONCLUSIONS: Even small compartments of the fetal brain, which are not easily accessible by standardized two-dimensional modalities, can be assessed precisely by super-resolution processed fetal MRI. The inverse growth dynamics of GE volume compared with TBV and cortical volume reflects the transitory nature and physiological involution of this (patho-)physiologically important brain structure. The normal development and involution of the GE is mandatory for normal cortical development. Pathological changes of this transient organ precede impairment of cortical structures, and their detection may allow an earlier diagnosis of such anomalies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A computational neuroimaging study of reinforcement learning and goal-directed exploration in schizophrenia spectrum disorders.

BACKGROUND: Prior evidence indicates that negative symptom severity and cognitive deficits, in people with schizophrenia (PSZ), relate to measures of reward-seeking and loss-avoidance behavior (implicating the ventral striatum/VS), as well as uncertainty-driven exploration (reliant on rostrolateral prefrontal cortex/rlPFC). While neural correlates of reward-seeking and loss-avoidance have been examined in PSZ, neural correlates of uncertainty-driven exploration have not. Understanding neural correlates of uncertainty-driven exploration is an important next step that could reveal insights to how this mechanism of cognitive and negative symptoms manifest at a neural level. METHODS: We acquired fMRI data from 29 PSZ and 36 controls performing the Temporal Utility Integration decision-making task. Computational analyses estimated parameters corresponding to learning rates for both positive and negative reward prediction errors (RPEs) and the degree to which participates relied on representations of relative uncertainty. Trial-wise estimates of expected value, certainty, and RPEs were generated to model fMRI data. RESULTS: Behaviorally, PSZ demonstrated reduced reward-seeking behavior compared to controls, and negative symptoms were positively correlated with loss-avoidance behavior. This finding of a bias toward loss avoidance learning in PSZ is consistent with previous work. Surprisingly, neither behavioral measures of exploration nor neural correlates of uncertainty in the rlPFC differed significantly between groups. However, we showed that trial-wise estimates of relative uncertainty in the rlPFC distinguished participants who engaged in exploratory behavior from those who did not. rlPFC activation was positively associated with intellectual function. CONCLUSIONS: These results further elucidate the nature of reinforcement learning and decision-making in PSZ and healthy volunteers.

Somatosensory and motor representations following bilateral transplants of the hands: A 6-year longitudinal case report on the first pediatric bilateral hand transplant patient.

A vascularized composite tissue allotransplantation (VCA) was performed at the Children's Hospital of Philadelphia (CHOP), on an 8-year-old patient in 2015, six years after bilateral hand and foot amputation. Hand VCA resulted in reafferentation of the medial, ulnar, and radial nerves serving hand somatosensation and motor function. We used magnetoencephalography (MEG) to assess somatosensory cortical plasticity following the post-transplantation recovery of the peripheral sensory nerves of the hands. Our 2-year postoperative MEG showed that somatosensory lip representations, initially observed at "hand areas", reverted to canonical, orthotopic lip locations with recovery of post-transplant hand function. Here, we continue the assessment of motor and somatosensory responses up to 6-years post-transplant. Magnetoencephalographic somatosensory responses were recorded eight times over a six-year period following hand transplantation, using a 275-channel MEG system. Somatosensory tactile stimuli were presented to the right lower lip (all 8 visits) as well as right and left index fingers (visits 3-8) and fifth digits (visits 4-8). In addition, left and right-hand motor responses were also recorded for left index finger and right thumb (visit 8 only).During the acute recovery phase (visits 3 and 4), somatosensory responses of the digits were observed to be significantly larger and more phasic (i.e., smoother) than controls. Subsequent measures showed that digit responses maintain this atypical response profile (evoked-response magnitudes typically exceed 1 picoTesla). Orthotopic somatosensory localization of the lip, D2, and D5 was preserved. Motor beta-band desynchrony was age-typical in localization and response magnitude; however, the motor gamma-band response was significantly larger than that observed in a reference population.These novel findings show that the restoration of somatosensory input of the hands resulted in persistent and atypically large cortical responses to digit stimulation, which remain atypically large at 6 years post-transplant; there is no known perceptual correlate, and no reports of phantom pain. Normal somatosensory organization of the lip, D2, and D5 representation remain stable following post-recovery reorganization of the lip's somatosensory response.

ACR White Paper on Magnetoencephalography and Magnetic Source Imaging: A Report from the ACR Commission on Neuroradiology.

Magnetoencephalography, the extracranial detection of tiny magnetic fields emanating from intracranial electrical activity of neurons, and its source modeling relation, magnetic source imaging, represent a powerful functional neuroimaging technique, able to detect and localize both spontaneous and evoked activity of the brain in health and disease. Recent years have seen an increased utilization of this technique for both clinical practice and research, in the United States and worldwide. This report summarizes current thinking, presents recommendations for clinical implementation, and offers an outlook for emerging new clinical indications.

Reciprocal associations of posttraumatic stress symptoms and cognitive decline in community-dwelling older adults: The mediating role of depression.

BACKGROUND: People with posttraumatic stress disorder (PTSD) may have cognitive decline, a risk which can be particularly threatening at old age. However, it is yet unclear whether initial cognitive decline renders one more susceptible to subsequent PTSD following exposure to traumatic events, whether initial PTSD precedes cognitive decline or whether the effects are reciprocal. OBJECTIVE: This study examined the bidirectional longitudinal associations between cognitive function and PTSD symptoms and whether this association is mediated by depressive symptoms. METHOD: The study used data from two waves of the Israeli component of the Survey of Health, Ageing, and Retirement in Europe (SHARE), collected in 2013 and 2015. This study focused on adults aged 50 years and above (N = 567, mean age = 65.9 years). Each wave used three measures of cognition (recall, fluency, and numeracy) and PTSD symptoms following exposure to war-related events. Data were analyzed using mediation analysis with path analysis. RESULTS: Initial PTSD symptoms predicted cognitive decline in recall and fluency two years later, while baseline cognitive function did not impact subsequent PTSD symptoms. Partial mediation showed that older adults with more PTSD symptoms had higher depressive symptoms, which in turn were linked to subsequent cognitive decline across all three measures. CONCLUSIONS: This study reveals that PTSD symptoms are linked with subsequent cognitive decline, supporting approaches addressing this direction. It further indicates that part of this effect can be explained by increased depressive symptoms. Thus, treatment for depressive symptoms may help reduce cognitive decline due to PTSD.

Validation of the National Institute of Neurological Disorders and Stroke Spinal Cord Injury MRI Common Data Elements Instrument.

BACKGROUND AND PURPOSE: The National Institute of Neurological Disorders and Stroke common data elements initiative was created to provide a consistent method for recording and reporting observations related to neurologic diseases in clinical trials. The purpose of this study is to validate the subset of common data elements related to MR imaging evaluation of acute spinal cord injury. MATERIALS AND METHODS: Thirty-five cervical and thoracic MR imaging studies of patients with acute spinal cord injury were evaluated independently in 2 rounds by 5 expert reviewers. Intra- and interrater agreement were calculated for 17 distinct MR imaging observations related to spinal cord injury. These included ordinal, categoric, and continuous measures related to the length and location of spinal cord hemorrhage and edema as well as spinal canal and cord measurements. Level of agreement was calculated using the interclass correlation coefficient and kappa. RESULTS: The ordinal common data elements spinal cord injury elements for lesion center and rostral or caudal extent of edema or hemorrhage demonstrated agreement ranging from interclass correlation coefficient 0.68 to 0.99. Reproducibility ranged from 0.95 to 1.00. Moderate agreement was observed for absolute length of hemorrhage and edema (0.54 to 0.60) with good reproducibility (0.78 to 0.83). Agreement for the Brain and Spinal Injury Center score showed the lowest interrater agreement with an overall kappa of 0.27 (0.20, 0.34). For 7 of the 8 variables related to spinal cord injury, agreement improved between the first and second evaluation. Continuous diameter measures of the spinal cord and spinal canal using interclass correlation coefficient varied substantially (0.23 to 0.83). CONCLUSIONS: Agreement was more consistent for the ordinal measures of spinal cord injury than continuous measures. Good to excellent agreement on length and location of spinal cord hemorrhage and edema can be achieved with ordinal measures alone.

From hydroxychloroquine to ivermectin: what are the anti-viral properties of anti-parasitic drugs to combat SARS-CoV-2?

BACKGROUND: Nearly a year into the COVID-19 pandemic, we still lack effective anti-SARS-CoV-2 drugs with substantial impact on mortality rates except for dexamethasone. As the search for effective antiviral agents continues, we aimed to review data on the potential of repurposing antiparasitic drugs against viruses in general, with an emphasis on coronaviruses. METHODS: We performed a review by screening in vitro and in vivo studies that assessed the antiviral activity of several antiparasitic agents: chloroquine, hydroxychloroquine (HCQ), mefloquine, artemisinins, ivermectin, nitazoxanide (NTZ), niclosamide, atovaquone and albendazole. RESULTS: For HCQ and chloroquine we found ample in vitro evidence of antiviral activity. Cohort studies that assessed the use of HCQ for COVID-19 reported conflicting results, but randomized controlled trials (RCTs) demonstrated no effect on mortality rates and no substantial clinical benefits of HCQ used either for prevention or treatment of COVID-19. We found two clinical studies of artemisinins and two studies of NTZ for treatment of viruses other than COVID-19, all of which showed mixed results. Ivermectin was evaluated in one RCT and few observational studies, demonstrating conflicting results. As the level of evidence of these data is low, the efficacy of ivermectin against COVID-19 remains to be proven. For chloroquine, HCQ, mefloquine, artemisinins, ivermectin, NTZ and niclosamide, we found in vitro studies showing some effects against a wide array of viruses. We found no relevant studies for atovaquone and albendazole. CONCLUSIONS: As the search for an effective drug active against SARS-CoV-2 continues, we argue that pre-clinical research of possible antiviral effects of compounds that could have antiviral activity should be conducted. Clinical studies should be conducted when sufficient in vitro evidence exists, and drugs should be introduced into widespread clinical use only after being rigorously tested in RCTs. Such a search may prove beneficial in this pandemic or in outbreaks yet to come.

Direct Measurements of Collisional Dynamics in Cold Atom Triads.

The introduction of optical tweezers for trapping atoms has opened remarkable opportunities for manipulating few-body systems. Here, we present the first bottom-up assembly of atom triads. We directly observe atom loss through inelastic collisions at the single event level, overcoming the substantial challenge in many-atom experiments of distinguishing one-, two-, and three-particle processes. We measure a strong suppression of three-body loss, which is not fully explained by the presently availably theory for three-body processes. The suppression of losses could indicate the presence of local anticorrelations due to the interplay of attractive short range interactions and low dimensional confinement. Our methodology opens a promising pathway in experimental few-body dynamics.

Clinical and aesthetic outcome analysis of a case series of trigonocephaly patients after early fronto-orbital advancement.

The timing of operation for trigonocephaly is recommended before the age of 1 year. To evaluate the outcome of a consecutive series operated in a single centre, the current study was performed. The study cohort comprised a retrospective single-centre series of 20 patients with trigonocephaly operated before the age of 12 months. Intra- and postoperative clinical data, as well as aesthetic outcome measured by two-dimensional asymmetry index (2D AI) and correction of the curvature on lateral and pictures from above were evaluated. Furthermore, to evaluate postoperative aesthetic outcome, a new classification (Grades I-IV) was proposed. The mean age of the cohort was 7.9 months. 2D AI changed from 0.049 pre- to 0.03 postoperatively (P=0.165). The correction of the curvature in lateral pictures yielded a significant change on postoperative pictures (P=0.002) as well as on pictures from above. Using the proposed classification, 16/20 (80%) patients had a postoperative outcome of Grade I, 4/20 (20%) Grade II. In patients operated before the age of 12 months an excellent (Grade I, AI <0.03) or good aesthetic (Grade II, adequate parents' or surgeon's opinion) result could be reached in all patients.

Screening and exclusion of Zika virus infection in travellers by an NS1-based ELISA and qRT-PCR.

OBJECTIVES: Zika virus (ZIKV) infection during pregnancy may cause neurological abnormalities in the foetus, and therefore fast and accurate laboratory assays are critical for rapid diagnosis. ELISA based on ZIKV NS1 protein has been developed and shown to be sensitive and highly specific; however, its negative and positive predictive values have not been tested. In this study we evaluated the ability of the NS1-based ELISA to exclude ZIKV infection and serve as a first-line screening tool for travellers. METHODS: We tested samples obtained during the peak of ZIKV infection from 1188 symptomatic and asymptomatic Israeli travellers using NS1-based IgG and IgM ELISA, real-time RT-PCR analysis and ZIKV neutralization. The Kaplan-Maier method was used to evaluate the duration of ZIKV RNA in whole blood and urine samples. RESULTS: NS1-based ELISA identified 20 true-positive, five false-positive and four false-negative cases, resulting in sensitivity and specificity of 83.3% (95%CI: 62-94%) and 97.5% (95%CI: 94-99%) respectively, and positive and negative predictive values of 80% (95%CI: 59-92%) and 98% (95%CI: 95-99%) respectively. Based on 14 RT-PCR-positive cases, median time to detect ZIKV RNA in whole blood was 17.5 days (range 5-58 days) and in urine 10 days (range 5-26 days). CONCLUSIONS: The NS1-based ELISA and RT-PCR in whole blood are highly reliable for identification of ZIKV-negative and -positive cases, respectively. Combination of both assays minimizes the risk of false-negative results, and thus allows the exclusion of ZIKV infection in travellers returning from ZIKV-endemic countries, including those who are pregnant or wish for preconception screening.

Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula.

The unconventional N-methyl-d-aspartate (NMDA) receptor subunits GluN3A and GluN3B can, when associated with the other glycine-binding subunit GluN1, generate excitatory conductances purely activated by glycine. However, functional GluN1/GluN3 receptors have not been identified in native adult tissues. We discovered that GluN1/GluN3A receptors are operational in neurons of the mouse adult medial habenula (MHb), an epithalamic area controlling aversive physiological states. In the absence of glycinergic neuronal specializations in the MHb, glial cells tuned neuronal activity via GluN1/GluN3A receptors. Reducing GluN1/GluN3A receptor levels in the MHb prevented place-aversion conditioning. Our study extends the physiological and behavioral implications of glycine by demonstrating its control of negatively valued emotional associations via excitatory glycinergic NMDA receptors.

Synthetic aperture magnetometry and excess kurtosis mapping of Magnetoencephalography (MEG) is predictive of epilepsy surgical outcome in a large pediatric cohort.

OBJECTIVE: Resective surgery is the most effective treatment option for patients with refractory epilepsy; however identification of patients who will benefit from epilepsy surgery remains challenging. Synthetic aperture magnetometry and excess kurtosis mapping (SAM(g2)) of magnetoencephalography (MEG) is a non-invasive tool that warrants further examination in the pediatric epilepsy population. Here, we examined the utility of MEG with SAM(g2) to determine if MEG epileptiform foci correlates with surgical outcome and to develop a predictive model incorporating MEG information to best assess likelihood of seizure improvement/freedom from resective surgery. METHODS: 564 subjects who had MEG at the Children's Hospital of Philadelphia between 2010-2015 were screened. Clinical epilepsy history and prior electrographic records were extracted and reviewed and correlated with MEG findings. MEG assessments were made by both a neurologist and neuroradiologist. Predictive models were developed to assess the utility of MEG in determining Engel class at one year and five years after resective epilepsy surgery. RESULTS: The number of MEG spike foci was highly associated with Engel class outcome at both one year and five years; however, using MEG data in isolation was not significantly predictive of 5 year surgical outcome. When combined with clinical factors; scalp EEG (single ictal onset zone), MRI (lesional or not), age and sex in a logistic regression model MEG foci was significant for Engel class outcome at both 1 year (p = 0.03) and 5 years (0.02). The percent correctly classified for Engel class at one year was 78.43% and the positive predictive value was 71.43. SIGNIFICANCE: MEG using SAM(g2) analysis in an important non-invasive tool in the identification of those patients who will benefit most from surgery. Integrating MEG data analysis into pre-surgical evaluation can help to predict epilepsy outcome after resective surgery in the pediatric population if utilized with skilled interpretation.

Underdevelopment of the Human Hippocampus in Callosal Agenesis: An In Vivo Fetal MRI Study.

BACKGROUND AND PURPOSE: In subjects with agenesis of the corpus callosum, a variety of structural brain alterations is already present during prenatal life. Quantification of these alterations in fetuses with associated brain or body malformations (corpus callosum agenesis and other related anomalies) and so-called isolated cases may help to optimize the challenging prognostic prenatal assessment of fetuses with corpus callosum agenesis. This fetal MR imaging study aimed to identify differences in the size of the prenatal hippocampus between subjects with isolated corpus callosum agenesis, corpus callosum agenesis and other related anomalies, and healthy controls. MATERIALS AND METHODS: Eighty-five in utero fetal brain MR imaging scans, (20-35 gestational weeks) were postprocessed using a high-resolution algorithm. On the basis of multiplanar T2-TSE sequences, 3D isovoxel datasets were generated, and both hippocampi and the intracranial volume were segmented. RESULTS: Hippocampal volumes increased linearly with gestational weeks in all 3 groups. One-way ANOVA demonstrated differences in hippocampal volumes between control and pathologic groups (isolated corpus callosum agenesis: left, P = .02; right, P = .04; corpus callosum agenesis and other related anomalies: P < .001). Differences among the pathologic groups were also present for both sides. Intracranial volume and right and left hippocampal volume ratios were different between corpus callosum agenesis cases and controls (P < .001). When we corrected for intracranial volume, no differences were found between corpus callosum agenesis and other associated anomalies and isolated corpus callosum agenesis (left, P = .77; right, P = .84). Hippocampal size differences were more pronounced at a later gestational age. CONCLUSIONS: Callosal agenesis apparently interferes with the normal process of hippocampal formation and growth, resulting in underdevelopment, which could account for certain learning and memory deficits in individuals with agenesis of the corpus callosum in later life.

Nursing care for migrant and refugee families: emerging issue

The impact of migratory movements is, worldwide, an emerging theme for nursing because of the health implications of individuals and their migrant or refugee families. These movements, whether voluntary or involuntary, are motivated by social, economic, cultural, religious or environmental factors.1International migration is a concern for achieving the goals of the Sustainable Development Agenda 2030 and it is estimated that 258 million people live in a country other than their birth, of which 68.5 million are refugees and represents an increase of 49% since 2000.2The terms migrants and refugees are used interchangeably, but their meanings are different. Refugees are out of their country of origin because they fear persecution, conflict, violence or other circumstances that impose the need for "international protection." Already, migrant individuals live a voluntary process; for example, someone who crosses a border in search of better economic opportunities.3These movements bring significant socio-cultural impacts related to the abandonment of material goods; loss of employment; undocumented status, food insecurity, increased morbidity and mortality. In addition, the process of acculturation involves the rupture of social networks, changes in the way of life, uprooting, humiliation and the sensation of not belonging to any place. These are barriers that influence the level of health of families.4

Perspectives on Neuroradiology Medical Expert Testimony: Fact and Fiction.

There are numerous misconceptions about serving as a medical malpractice expert witness. By maintaining an objective perspective based in the unbiased interpretation of the images provided (for both sides of the conflict), one can best serve society as a whole. Most cases for which a neuroradiology expert is recruited are the following: 1) not with the radiologist as a defendant, 2) resolved without court testimony, and 3) short-lived if frivolous. One can learn much about medicine, our nonradiology colleagues, and the litigation process by participating as an expert witness.

Experiência do adulto jovem com a doença renal crônica emhemodiálise / Living of a young adult with chronic kidney disease under hemodialysis

Objetivo: conhecer o cotidiano do adulto jovem com a doença renal crônica em tratamento hemodialítico. Métodos: pesquisa qualitativa, exploratória e descritiva, realizada com oito informantes em um serviço de nefrologia e no domicílio em um município no Sul do Brasil, no período de junho a agosto de 2013. Utilizou-se como referencial teórico, conceitos relacionados aos aspectos culturais de Madelaine Leininger e Clifford Geertz e os instrumentos para a coleta de dados foram a entrevista narrativa, a observação assistemática e o diário de campo. Resultados: os informantes estabeleceram uma nova história, devido à convivência cotidiana com a doença, apresentando modificações nos hábitos alimentares, hídricos, atividades diárias, laborais, lazer e sexual. A dependência de outras pessoas também foi mencionada. As fontes de apoio estiveram presentes nas narrativas. Considerações finais: os adultos jovens nessa condição de adoecimento construíram um novo modo de viver baseado em sua cultura, mantendo normas, valores e crenças.

Objective: to know the experience of a young adult with chronic kidney disease under hemodialysis.Methods: qualitative, exploratory and descriptive research, performed with eight informants in aservice of nephrology, and in a home in a city of south of Brazil, during June to August 2013. Thetheoretical referential concepts of Madelaine Leininger and Clifford Geertz was used, and theinstruments for the data collection were the narrative interview, the systematic observation, and afield diary. Data analysis was by Minayo. Results: the informants established a new history, due tothe everyday living with the disease, presenting changes in the habits of life. Dependence on otherpeople and sources of support such as family, people known or not, health team were mentioned.Final Considerations: young adults in this condition of illness built a new way of living, which isbased on their culture, keeping rules, values and beliefs.

On-chip free beam optics on a polymer-based photonic integration platform.

This paper presents on-chip free beam optics on polymer-based photonic components. Due to the circumstance that waveguide-based optics allows no direct beam access we use Gradient index (GRIN) lenses assembled into the chip to collimate the beam from the waveguides. This enables low loss power transmission over a length of 1432 µm. Even though the beam propagates through air it is possible to create a resonator with a wavelength shift of 0.002 nm/°C, hence the allowed deviations from the ITU-T grid (100 GHz) are met for ± 20 °C. In order to guarantee reliable laser stability, it is necessary to implement optical isolators at the output of the laser. This requires the insertion of bulk material into the chip and is realized by a 1050 µm thick coated glass. Due to the large gap of the free-space section, it is possible to combine different resonators together. This demonstrates the feasibility of an integrated wavelength-meter.