Brain Point of Care Ultrasound in Young Children Receiving Computed Tomography in the Emergency Department: A Proof of Concept Study.

Background: Point of Care Ultrasound (POCUS) is an important tool in pediatric emergency medicine. In neonatal intensive care medicine ultrasound is often used to evaluate the brains of sick neonates. In theory, POCUS could be used in the ED in young children to evaluate the brain for abnormal pathology. Objectives: To examine the ability of PEM faculty to use brain POCUS to identify clinically significant brain injuries in children with head injuries and/or abnormal neurological exams, and generate sensitivity and specificity of brain POCUS in assessing such findings. Methods: This study used a convenience sample of patients seen in a tertiary care pediatric centre who required a CT head. A team of physicians who were trained at a workshop for brain POCUS were on call to perform the POCUS while being blinded to the results of the CT. Results: 21 children were enrolled in the study. Five (24%) of the patients had a CT that was positive for intracranial bleeds. Of the 5 patients with a positive CT, 3 had a brain POCUS scan that was also positive. The two false negative brain POCUS scans were on patients with small bleeds (no surgical intervention required) on CT, as reported by radiology. The sensitivity of brain POCUS was 60% (CI 15% - 95%) with a specificity of 94% (CI 70%-100%). The diagnostic accuracy of brain POCUS was 86% (CI 64% - 97%). Conclusion: This small proof of concept study shows that brain POCUS is an imaging modality with reasonable sensitivity and specificity in identifying intracranial pathologies that are present on CT. Its use may be most beneficial to expedite definitive imaging and subspeciality involvement.

The mitochondrial tRNA MT-TW m.5537_5538insT variant presents with significant intra-familial clinical variability.

Mitochondrial disorders can present with a wide range of clinical and biochemical phenotypes. Mitochondrial DNA variants may be influenced by factors such as degree of heteroplasmy and tissue distribution. We present a four-generation family in which 10 individuals carry a pathogenic mitochondrial variant (m.5537_5538insT, MT-TW gene) with differing levels of heteroplasmy and clinical features. This genetic variant has been documented in two prior reports, both in individuals with Leigh syndrome. In the current family, three individuals have severe mitochondrial symptoms including Leigh syndrome (patient 1, 100% in blood), MELAS (patient 2, 97% heteroplasmy in muscle), and MELAS-like syndrome (patient 3, 50% heteroplasmy in blood and 100% in urine). Two individuals have mild mitochondrial symptoms (patient 4, 50% in blood and 67% in urine and patient 5, 50% heteroplasmy in blood and 30% in urine). We observe that this variant is associated with multiple mitochondrial presentations and phenotypes, including MELAS syndrome for which this variant has not previously been reported. We also demonstrate that the level of heteroplasmy of the mitochondrial DNA variant correlates with the severity of clinical presentation; however, not with the specific mitochondrial syndrome.

Strength and Microstructure Assessment of Partially Replaced Ordinary Portland Cement and Calcium Sulfoaluminate Cement with Pozzolans and Spent Coffee Grounds.

Supplementary cementitious materials are considered a viable and affordable way to reduce CO2 emissions from the cement industry's perspective since they can partially or nearly entirely replace ordinary Portland cement (OPC). This study compared the impact of adding spent coffee grounds (SCGs), fly ash (FA), and volcanic ash (VA) to two types of cement: OPC and calcium sulfoaluminate cement (CSA). Cement samples were characterized using compressive strength measurements (up to 210 days of curing), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS), X-ray diffraction (XRD), attenuated total reflection infrared spectroscopy, and hydration temperature measurements. In all the studied systems, the presence of SCGs reduced compressive strength and delayed the hydration process. CSA composite cement containing 3.5% SCGs, 30% FA, and 30% VA showed compressive strength values of 20.4 MPa and 20.3 MPa, respectively, meeting the minimum requirement for non-structural applications. Additionally, the results indicate a formation of cementitious gel, calcium silicate hydrate (C-S-H) in the OPC-based composite cements, and calcium alumino-silicate hydrate (C-A-S-H) as well as ettringite in the CSA-based composite cements.

MR Enterography Scores Correlate with Degree of Mucosal Healing in Pediatric Crohn's Disease: A Pilot Study.

Objectives: MR enterography (MRE) Index of Activity (MaRIA) and Clermont are validated scores that correlate with Crohn's disease (CD) activity; however, the Clermont score has not been validated to correlate with the degree of change in mucosal inflammation post induction treatment in children. This pilot study evaluated if MaRIA and Clermont scores can serve as surrogates to ileocolonoscopy for assessing interval change in mucosal inflammation in pediatric CD post-induction treatment. Methods: Children with known or newly diagnosed ileocolonic CD starting or changing therapy underwent ileocolonoscopy, scored with simple endoscopic score for Crohn's disease (SES-CD), and MRE on the same day at two time points (Week 0 and 12). Accuracy of global MaRIA and Clermont indices relative to ileocolonoscopy in detecting degree of post-treatment interval change in mucosal inflammation was assessed through correlational coefficients (r). Inter-reader agreement was calculated for imaging scores through intraclass correlation (ICC). Results: Sixteen children (mean age 11.5 ± 2.8) were evaluated. Global MaRIA/Clermont correlated with SES-CD in detecting the degree of change in mucosal inflammation (r = 0.676 and r = 0.677, P < 0.005, respectively). Correlation for pooled timepoint assessments between SES-CD and global MaRIA/Clermont was moderate (r = 0.546, P < 0.001 and r = 0.582, P < 0.001, respectively). Inter-rater reliability for global MaRIA and Clermont was good (ICC = 0.809 and ICC = 0.768, respectively, P < 0.001). Conclusions: MRE-based global scores correlate with endoscopic indices and may be used to monitor disease changes in children with CD undergoing induction treatment, which can advise the physician if treatment changes should be made.

Factores que afectan la estabilidad de los implantes dentales según la medición del coeficiente de estabilidad del implante (ISQ). Una revisión sistemática de la literatura / Factors affecting dental implants stability as measured by the implant stability quotient (ISQ). A systematic review of the literature

Antecedentes: La estabilidad en los implantes dentales colocados en los huesos alveolares es un parámetro importante para el éxito del tratamiento y su oseointegración. Los factores que pueden afectar la estabilidad son: densidad ósea, el macrodiseño/microdiseño de los implantes, el diseño quirúrgico, la carga y el sexo; estos se pueden evaluar mediante la obtención de valores del análisis de frecuencia de resonancia (RFA) interpretados como el coeficiente de estabilidad del implante (ISQ). Objetivo: Evaluar los factores que pueden afectar la estabilidad de los implantes mediante valores ISQ medidos con el dispositivo Osstell. Materiales y métodos: Para esta revisión sistemática se realizó una búsqueda en bases de datos: PubMed, Scopus, EBSCO, Science-direct y Cochrane de artículos publicados entre enero del 2015 y diciembre del 2021. Se realizó la elección de estudios clínicos aleatorizados, revisiones sistemáticas y metanálisis basados en el manual de Cochrane. Un total de 26 artículos cumplían con los criterios de inclusión y exclusión. Resultados: Fueron evaluados un total de 3047 implantes en 1367 pacientes. Los factores estudiados fueron: densidad ósea, macrodiseño/microdiseño del implante, técnica quirúrgica, carga y sexo. La densidad ósea es el factor que más afecta la estabilidad primaria de un implante, mientras que el microdiseño es el factor que más influye para la estabilidad secundaria.Conclusiones: Tanto la estabilidad primaria y secundaria de un implante dependen de la interacción de varios factores. Es importante individualizar cada caso y analizar cada uno de los factores con el fin de tomar decisiones acertadas y basadas en evidencia que permitan obtener resultados predecibles. (AU)

Background: Dental implants stability placed on the alveolar ridge is considered an important factor to evaluate the treatment success and its osseointegration. Factors that seem to affect the stability are: bone density, implant macro/micro design, surgical protocol, loading and sex. These factors may be evaluated by the measurement of resonance frequency analysis (RFA) resulting as the Implant Stability Quotient (ISQ). Objective: To review the literature on the factors that can affect the stability of dental implants considering the ISQ values measured with the Osstell device. Materials and methods: A systematic search of the literature was carried out in the following databases: PubMed, Scopus, EBSCO, Science direct y Cochrane of articles published between January 2015 and December 2021. Randomized controlled trials, systematic reviews and metanalysis were selected based on the Cochrane handbook for systematic reviews. A total of 26 articles were selected and analyzed based on our inclusion and exclusion criteria. Results: In the 26 articles selected, 3047 implants were evaluated placed in 1367 patients. The most studied factors were: bone density, implant macro design, implant micro design, surgical technique, implant loading and genre. Bone density is the factor that influence the most when studying primary stability. For secondary stability, implant micro design has a direct relationship according to resonance frequency analysis (RFA). Conclusions: Primary and secondary stability depends on many factors. It is important to individualize each patient and evaluate each factor for decision making based on evidence and have a more predictable outcome when placing dental implants. (AU)

White Button Mushroom (Agaricus bisporus) Supplementation Ameliorates Spatial Memory Deficits and Plaque Formation in an Amyloid Precursor Protein Mouse Model of Alzheimer's Disease.

Alzheimer's Disease (AD) is characterized by cognitive impairment and the presence of amyloid-ß (Aß) plaques and tau tangles. This study was conducted to assess the effects of white button mushroom (WBM) supplementation on spatial memory and plaque formation in mice with mutations in amyloid (Aß). Mice with amyloid precursor protein (hAPP) mutations and their wildtype (WT) littermates were fed a 10% white button mushroom (WBM) feed ad libitum three times per week, in addition to their normal diet. Morris water maze (MWM) was conducted at 14 and 32 weeks of age to assess spatial memory and Aß plaque pathology in the hippocampus was analyzed. Our results showed that hAPP mice on the WBM diet were faster in reaching the platform in the MWM compared to hAPP mice on the control diet at 32 weeks (p < 0.05). Significantly fewer plaque deposits were found in the hippocampi of hAPP mice on the WBM diet compared to those on the control diet at 32 weeks (p < 0.05). Overall, hAPP mice on the WBM diet had improved spatial memory at 32 weeks of age compared to those on the control diet and exhibited fewer amyloid plaques.

The White Matter Rounds experience: The importance of a multidisciplinary network to accelerate the diagnostic process for adult patients with rare white matter disorders.

Introduction: Adult genetic leukoencephalopathies are rare neurological disorders that present unique diagnostic challenges due to their clinical and radiological overlap with more common white matter diseases, notably multiple sclerosis (MS). In this context, a strong collaborative multidisciplinary network is beneficial for shortening the diagnostic odyssey of these patients and preventing misdiagnosis. The White Matter Rounds (WM Rounds) are multidisciplinary international online meetings attended by more than 30 physicians and scientists from 15 participating sites that gather every month to discuss patients with atypical white matter disorders. We aim to present the experience of the WM Rounds Network and demonstrate the value of collaborative multidisciplinary international case discussion meetings in differentiating and preventing misdiagnoses between genetic white matter diseases and atypical MS. Methods: We retrospectively reviewed the demographic, clinical and radiological data of all the subjects presented at the WM Rounds since their creation in 2013. Results: Seventy-four patients (mean age 44.3) have been referred and discussed at the WM Rounds since 2013. Twenty-five (33.8%) of these patients were referred by an MS specialist for having an atypical presentation of MS, while in most of the remaining cases, the referring physician was a geneticist (23; 31.1%). Based on the WM Rounds recommendations, a definite diagnosis was made in 36/69 (52.2%) patients for which information was available for retrospective review. Of these diagnosed patients, 20 (55.6%) had a genetic disease, 8 (22.2%) had MS, 3 (8.3%) had both MS and a genetic disorder and 5 (13.9%) had other non-genetic conditions. Interestingly, among the patients initially referred by an MS specialist, 7/25 were definitively diagnosed with MS, 5/25 had a genetic condition (e.g., X-linked adrenoleukodystrophy and hereditary small vessel diseases like Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) and COL4A1-related disorder), and one had both MS and a genetic demyelinating neuropathy. Thanks to the WM Rounds collaborative efforts, the subjects who currently remain without a definite diagnosis, despite extensive investigations performed in the clinical setting, have been recruited in research studies aimed at identifying novel forms of genetic MS mimickers. Conclusions: The experience of the WM Rounds Network demonstrates the benefit of collective discussions on complex cases to increase the diagnostic rate and decrease misdiagnosis in patients with rare or atypical white matter diseases. Networks of this nature allow physicians and scientists to compare and share information on challenging cases from across the world, provide a basis for future multicenter research studies, and serve as model for other rare diseases.

Is horseshoe lung a component of VACTERL spectrum? Case report and review of literature.

Horseshoe lung (HL) is a rare congenital anomaly that has been classically associated with Scimitar syndrome. Very few cases have been described in the context of the VACTERL spectrum. We present a case of a newborn girl with mesocardia, tracheoesophageal fistula, and imperforated anus, who required O2 support at birth and during hospitalization. A chest CT angiography revealed a HL as an incidental finding. We suspect that HL and the VACTERL spectrum, are not separated entities but likely a further expansion of VACTERL-associated symptoms. HL might be underdiagnosed in asymptomatic patients as Chest CT angiography is not part of the routine work up for patients with VACTERL association.

Burnout Syndrome in a Military Tertiary Hospital Staff during the COVID-19 Contingency.

(1) Background: Burnout syndrome (BOS) is defined as a psychological state of physical and mental fatigue associated with work. The COVID-19 pandemic greatly impacted the physical and mental wellbeing of health professionals. The objective of this work was to determine the impact on personnel, monitoring the frequency of BOS throughout the pandemic. (2) Methods: The Maslach Burnout Inventory (MBI) was self-applied in four periods of the pandemic according to sociodemographic and employment characteristics. In this study, all hospital personnel were included; the association of BOS with sex, age, type of participant (civilian or military), military rank and profession was analyzed. (3) Results: The frequency of BOS was 2.4% (start of the pandemic), 7.9% (peak of the first wave), 3.7% (end of the first wave) and 3.6% (peak of the third wave). Emotional exhaustion (EE) was the most affected factor, and the groups most affected were men under 30 years of age, civilians, chiefs and doctors, especially undergraduate medical doctors and specialty resident doctors, and nursing personnel were less affected. (4) Conclusions: The low BOS levels show that the containment measures and military training implemented by the hospital authorities were effective, although the chief personnel were more affected in the first wave. It is probable that this combination allowed the containment of BOS, which was not observed in civilians.

A De Novo Missense Variant in TUBG2 in a Child with Global Developmental Delay, Microcephaly, Refractory Epilepsy and Perisylvian Polymicrogyria.

Polymicrogyria is a brain malformation characterized by excessive folding of the cortex. To date, numerous causes of polymicrogyria have been identified, including variants in the genes associated with tubulinopathies. Herein, we present a child with severe intellectual disability, refractory to treatment seizures, microcephaly and MRI findings consistent with polymicrogyria, closed-lip schizencephaly, periventricular heterotopia and a dysplastic corpus callosum. Exome sequencing identified a de novo missense variant in TUBG2, a gene not associated with human disease. The variant, NM_016437.3 c.747G>A p.(Met249Ile), is absent from available control databases and is predicated to be deleterious by in silico prediction programs. Laboratory studies show that cultured lymphoblasts derived from the patient grew significantly faster than controls. Recombinant protein was expressed (recombinant wild type and mutant TUBG2-FLAG) in 293T cells and lower levels of TUBG2 mutant compared with controls were observed. Furthermore, co-immuno-precipitation in cells transfected demonstrated that the TUBG2−GCP2 interaction is increased due to the MUT recombinant protein versus WT recombinant protein. In closing, this work provides preliminary evidence that TUBG2 may represent a novel disease gene responsible for polymicrogyria.

Development and Validation of a Pediatric MRI-Based Perianal Crohn Disease (PEMPAC) Index-A Report from the ImageKids Study.

BACKGROUND: As part of the prospective multicenter ImageKids study, we aimed to develop and validate the pediatric MRI-based perianal Crohn disease (PEMPAC) index. METHODS: Children with Crohn disease with any clinical perianal findings underwent pelvic magnetic resonance imaging at 21 sites globally. The site radiologist and 2 central radiologists provided a radiologist global assessment (RGA) on a 100 mm visual analog scale and scored the items selected by a Delphi group of 35 international radiologists and a review of the literature. Two weighted multivariable statistical models were constructed against the RGA. RESULTS: Eighty children underwent 95 pelvic magnetic resonance imaging scans; 64 were used for derivation and 31 for validation. The following items were included: fistula number, location, length and T2 hyperintensity; abscesses; rectal wall involvement; and fistula branching. The last 2 items had negative beta scores and thus were excluded in a contending basic model. In the validation cohort, the full and the basic models had the same strong correlation with the RGA (r = 0.75; P < 0.01) and with the adult Van Assche index (VAI; r = 0.93 and 0.92; P < 0.001). The correlation of the VAI with the RGA was similar (r = 0.77; P < 0.01). The 2 models and the VAI had a similar ability to differentiate remission from active disease (area under the receiver operating characteristic curve, 0.91-0.94). The PEMPAC index had good responsiveness to change (area under the receiver operating characteristic curve, 0.89; 95% confidence interval, 0.69-1.00). CONCLUSIONS: Using a blended judgmental and mathematical approach, we developed and validated an index for quantifying the severity of perianal disease in children with CD. The adult VAI may also be used with confidence in children.

Whole genome sequencing identifies pathogenic RNU4ATAC variants in a child with recurrent encephalitis, microcephaly, and normal stature.

Biallelic pathogenic variants in RNU4ATAC have been linked to microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1). Although children with MOPD1 have been reported to show profound, life-limiting clinical decompensation at the time of a febrile illness, these episodes including magnetic resonance imaging (MRI) findings have not been well characterized. We present acute MRI brain findings for a 10-year-old girl with homozygous variants in RNU4ATAC (NR_023343.1) n.55G>A, who presented with two episodes of clinical decompensation associated with a febrile illness in early childhood. The pathogenic variants were identified by whole genome sequencing as RNU4ATAC is not captured in most exome products. Her MRI of the brain revealed symmetric, diffusion restriction of the deep gray nuclei that initially pointed to a mitochondrial disease or acute necrotizing encephalopathy. Her phenotype included microcephaly and profound cognitive impairment that can be seen with MOPD1. However, she did not demonstrate clinical or radiographic evidence of a spondyloepimetaphyseal dysplasia or "primordial dwarfism" that is characteristic of this disease. As such, the predominant neurological presentation of this child represents an atypical variant of RNU4ATAC-associated disease and should be a diagnostic consideration for geneticists and neurologists caring for children, particularly in the event of an acute clinical decline.

Comparison of Acute Effects of Neurotoxic Compounds on Network Activity in Human and Rodent Neural Cultures.

Assessment of neuroactive effects of chemicals in cell-based assays remains challenging as complex functional tissue is required for biologically relevant readouts. Recent in vitro models using rodent primary neural cultures grown on multielectrode arrays allow quantitative measurements of neural network activity suitable for neurotoxicity screening. However, robust systems for testing effects on network function in human neural models are still lacking. The increasing number of differentiation protocols for generating neurons from human-induced pluripotent stem cells (hiPSCs) holds great potential to overcome the unavailability of human primary tissue and expedite cell-based assays. Yet, the variability in neuronal activity, prolonged ontogeny and rather immature stage of most neuronal cells derived by standard differentiation techniques greatly limit their utility for screening neurotoxic effects on human neural networks. Here, we used excitatory and inhibitory neurons, separately generated by direct reprogramming from hiPSCs, together with primary human astrocytes to establish highly functional cultures with defined cell ratios. Such neuron/glia cocultures exhibited pronounced neuronal activity and robust formation of synchronized network activity on multielectrode arrays, albeit with noticeable delay compared with primary rat cortical cultures. We further investigated acute changes of network activity in human neuron/glia cocultures and rat primary cortical cultures in response to compounds with known adverse neuroactive effects, including gamma amino butyric acid receptor antagonists and multiple pesticides. Importantly, we observed largely corresponding concentration-dependent effects on multiple neural network activity metrics using both neural culture types. These results demonstrate the utility of directly converted neuronal cells from hiPSCs for functional neurotoxicity screening of environmental chemicals.

Whole-Body Diffusion-Weighted MRI Compared to 18 FFDG PET/CT in Initial Staging and Therapy Response Assessment of Hodgkin Lymphoma in Pediatric Patients.

PURPOSE: The aim of our study was to compare whole-body diffusion-weighted MRI (WB-DWI-MRI) to fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the assessment of initial staging and treatment response in pediatric patients with Hodgkin lymphoma. MATERIALS AND METHODS: This prospective study comprised 11 children with Hodgkin lymphoma. Whole-body DWI-MRI and FDG-PET/CT were obtained at baseline and after 2 cycles of chemotherapy. Two radiologists measured the apparent diffusion coefficient (ADC) values of the sites of involvement agreed upon in consensus and 1 nuclear medicine physician assessed the PET/CT. Reliability of radiologists' ratings was assessed by intraclass correlation coefficients (ICC2,1). The sensitivity and positive predictive value (PPV) of DW-MRI relative to PET/CT were calculated for nodal and extranodal sites. The patients were staged according to both modalities. Association of treatment responses was assessed through the Pearson correlation between the ADC ratios and the change standardized uptake value (SUV) between baseline and follow-up. RESULTS: There was good agreement between the raters for nodal and extranodal ADC measurements. The sensitivity and PPV of DW-MRI relative to PET/CT of nodal disease was 0.651 and 1.0, respectively, at baseline, and 0.697 and 0.885 at follow-up. The sensitivity and PPV of extranodal disease were 0.545 and 0.6 at baseline, and 0.167 and 0.333 at follow-up. Diffusion-weighted MRI determined correct tumor stage in 8 of 11 examinations. There was poor correlation between the ADC ratios and the absolute change in SUV between baseline and follow-up (0.348). CONCLUSION: Our experience showed that WB-DWI-MRI is inferior to PET/CT for initial staging and assessment of treatment response of Hodgkin lymphoma in pediatric patients.

Soft Tissue Lesions With High Vascular Density on Sonography in Pediatric Patients: Beyond Hemangiomas [Formula: see text].

Infantile hemangiomas are the most frequent vascular soft tissue lumps in the pediatric population. The clinical presentation and evolution of these lesions is characteristic, while the sonographic appearance is classic but not specific. This pictorial essay illustrates the different vascular soft tissue lumps on ultrasound that may mimic infantile hemangiomas. Awareness of these mimics is crucial to avoid misdiagnosis. Clinical and sonographic discriminators for each lesion are presented.

Influence of timing of initiation of therapeutic hypothermia on brain MRI and neurodevelopment at 18 months in infants with HIE: a retrospective cohort study.

OBJECTIVE: To examine the influence of timing of initiation of therapeutic hypothermia (TH) on brain injury on MRI and on neurodevelopmental outcomes at 18 months. DESIGN: Retrospective cohort study. SETTING: Tertiary neonatal intensive care unit in Ontario, Canada. PATIENTS: Ninety-one patients with hypoxic ischaemic encephalopathy (HIE) were included, 54 in the early TH group and 37 in the late TH group. INTERVENTION: Whole-body hypothermia administered for 72 hours, initiated either before 3 hours of life (early TH) or between 3 and 6 hours of life (late TH). MAIN OUTCOME MEASURES: Brain injury on MRI after TH (assessed by two neuroradiologists), and neurodevelopmental outcomes at 18 months old. RESULTS: TH was initiated at a median time of 1.4 hours (early TH) and 4.4 hours (late TH). Sixty-four neonates (early TH=36, late TH=28) survived and completed neurodevelopmental assessment at 18 months. Neonates in the early TH group received more extensive resuscitation than neonates in the late TH group (p=0.0008). No difference was observed between the two groups in the pattern or severity of brain injury on MRI, or in the neurodevelopmental outcomes at 18 months. The non-survivors (n=16) had lower Apgar scores at 10 min, more extensive resuscitation, suffered from more severe HIE and had significantly more abnormal cerebral function monitoring. CONCLUSION: In this retrospective cohort study, TH initiated early was associated neither with a difference in brain injury on MRI nor better neurodevelopmental outcomes at 18 months.