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Background: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID., Methods: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.)., Findings: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events., Interpretation: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions., Funding: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438., Competing Interests: Declaration of interests Danielle Mowery serves as an unpaid member of the Epic Cosmos Governing Council. Romain Pirracchio received funding from the FDA CERSI grant U01FD005978 and the PCORI grant P0562155 and received a consulting honorarium from Phillips. Martin van der Laan received funding from the NIAID grant 5R01AI074345. Johanna Loomba received contract funding from the NIH RECOVER program. Emily Pfaff received funding from the NIH and PCORI. The views expressed in this manuscript are solely those of the authors and do not necessarily represent those of the National Institutes of Health, the U.S. Department of Health and Human Services or the U.S. government. Qi Long was supported by grants from the NIH., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Despite recommendations by the United States Preventive Services Task Force and the Society for Vascular Surgery, adoption of screening for abdominal aortic aneurysms (AAAs) remains low. One challenge is the low prevalence of AAAs in the unscreened population, and therefore a low detection rate for AAA screenings. We sought to use machine learning to identify factors associated with the presence of AAAs and create a model to identify individuals at highest risk for AAAs, with the aim of increasing the detection rate of AAA screenings., Methods: A machine-learning model was trained using longitudinal medical records containing lab results, medications, and other data from our institutional database. A retrospective cohort study was performed identifying current or past smoking in patients aged 65 to 75 years and stratifying the patients by sex and smoking status as well as determining which patients had a confirmed diagnosis of AAA. The model was then adjusted to maximize fairness between sexes without significantly reducing precision and validated using six-fold cross validation., Results: Validation of the algorithm on the single-center institutional data utilized 18,660 selected patients over 2 years and identified 314 AAAs. There were 41 factors identified in the medical record included in the machine-learning algorithm, with several factors never having been previously identified to be associated with AAAs. With an estimated 100 screening ultrasounds completed monthly, detection of AAAs is increased with a lift of 200% using the algorithm as compared with screening based on guidelines. The increased detection of AAAs in the model-selected individuals is statistically significant across all cutoff points., Conclusions: By utilizing a machine-learning model, we created a novel algorithm to detect patients who are at high risk for AAAs. By selecting individuals at greatest risk for targeted screening, this algorithm resulted in a 200% lift in the detection of AAAs when compared with standard screening guidelines. Using machine learning, we also identified several new factors associated with the presence of AAAs. This automated process has been integrated into our current workflows to improve screening rates and yield of high-risk individuals for AAAs., Competing Interests: Disclosures A.L., T.S., and E.C. are employed by Medial EarlySign., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Research rarely explores LGBTQ+ youth bullying in the context of culture-specific outcomes (e.g., LGBTQ+ identity development) and what can mitigate the impact of peer stressors. This study used a concurrent mixed methods design to explore how experiences of peer victimization predicted LGBTQ+ youth's identity development (i.e., stigma sensitivity, concealment motivation, and difficult process) and whether social support and outness served as protective, moderating factors. The mixed methods approach provides a culture-specific context via qualitative inquiry to inform whether the quantitative findings align with how youth qualitatively discuss their experience of peer victimization, negative outcomes, and social support. Our sample consisted of 349 LGBTQ+ youth 14-17 years old who completed a survey (quantitative sample) and a subset of 39 LGBTQ+ youth who completed a semi-structured interview (qualitative sample). Our quantitative findings indicated that greater overall peer victimization was positively related to LGBIS-revised subscales of stigma sensitivity, concealment motivation, and difficult process, where both outness and social support moderated such relations. Qualitatively, victimized youth also reported stigma sensitivity and concealment motivation while also endorsing how being out and having a support system played a role in their experience of being victimized. These qualitative findings align with our quantitative findings that classmate support mitigated the effects of peer victimization on the difficulty of coming out. Implications for practitioners and researchers are provided.

Photothermal heating of nanoparticles has applications in nanomedicine, photocatalysis, photoelectrochemistry, and data storage, but accurate measurements of temperature at the nanoparticle surface are lacking. Here we demonstrate progress toward a super-resolution DNA nanothermometry technique capable of reporting the surface temperature on single plasmonic nanoparticles. Gold nanoparticles are functionalized with double-stranded DNA, and the extent of DNA denaturation under heating conditions serves as a reporter of temperature. Fluorescently labeled DNA oligomers are used to probe the denatured DNA through transient binding interactions. By counting the number of fluorescent binding events as a function of temperature, we reconstruct DNA melting curves that reproduce trends seen for solution-phase DNA. In addition, we demonstrate our ability to control the temperature of denaturation by changing the Na + concentration and the base pair length of the double-stranded DNA on the nanoparticle surface. This degree of control allows us to select narrow temperature windows to probe, providing quantitative measurements of temperature at nanoscale surfaces.

Background: An outbreak of coronavirus disease 2019 (Covid-19) occurred on the U.S.S. Theodore Roosevelt , a nuclear-powered aircraft carrier with a crew of 4779 personnel., Methods: We obtained clinical and demographic data for all crew members, including results of testing by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). All crew members were followed up for a minimum of 10 weeks, regardless of test results or the absence of symptoms., Results: The crew was predominantly young (mean age, 27 years) and was in general good health, meeting U.S. Navy standards for sea duty. Over the course of the outbreak, 1271 crew members (26.6% of the crew) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by rRT-PCR testing, and more than 1000 infections were identified within 5 weeks after the first laboratory-confirmed infection. An additional 60 crew members had suspected Covid-19 (i.e., illness that met Council of State and Territorial Epidemiologists clinical criteria for Covid-19 without a positive test result). Among the crew members with laboratory-confirmed infection, 76.9% (978 of 1271) had no symptoms at the time that they tested positive and 55.0% had symptoms develop at any time during the clinical course. Among the 1331 crew members with suspected or confirmed Covid-19, 23 (1.7%) were hospitalized, 4 (0.3%) received intensive care, and 1 died. Crew members who worked in confined spaces appeared more likely to become infected., Conclusions: SARS-CoV-2 spread quickly among the crew of the U.S.S. Theodore Roosevelt . Transmission was facilitated by close-quarters conditions and by asymptomatic and presymptomatic infected crew members. Nearly half of those who tested positive for the virus never had symptoms., (Copyright © 2020 Massachusetts Medical Society.)

Birth rates in the United States have recently fallen. Birth rates per 1000 females aged 25-29 fell from 118 in 2007 to 105 in 2015. One factor may involve the vaccination against the human papillomavirus (HPV). Shortly after the vaccine was licensed, several reports of recipients experiencing primary ovarian failure emerged. This study analyzed information gathered in National Health and Nutrition Examination Survey, which represented 8 million 25-to-29-year-old women residing in the United States between 2007 and 2014. Approximately 60% of women who did not receive the HPV vaccine had been pregnant at least once, whereas only 35% of women who were exposed to the vaccine had conceived. For married women, 75% who did not receive the shot were found to conceive, while only 50% who received the vaccine had ever been pregnant. Using logistic regression to analyze the data, the probability of having been pregnant was estimated for females who received an HPV vaccine compared with females who did not receive the shot. Results suggest that females who received the HPV shot were less likely to have ever been pregnant than women in the same age group who did not receive the shot. If 100% of females in this study had received the HPV vaccine, data suggest the number of women having ever conceived would have fallen by 2 million. Further study into the influence of HPV vaccine on fertility is thus warranted.

Conflicts of interest (COIs) cloud vaccine safety research. Sponsors of research have competing interests that may impede the objective study of vaccine side effects. Vaccine manufacturers, health officials, and medical journals may have financial and bureaucratic reasons for not wanting to acknowledge the risks of vaccines. Conversely, some advocacy groups may have legislative and financial reasons to sponsor research that finds risks in vaccines. Using the vaccine-autism debate as an illustration, this article details the conflicts of interest each of these groups faces, outlines the current state of vaccine safety research, and suggests remedies to address COIs. Minimizing COIs in vaccine safety research could reduce research bias and restore greater trust in the vaccine program.

The reason for the rapid rise of autism in the United States that began in the 1990s is a mystery. Although individuals probably have a genetic predisposition to develop autism, researchers suspect that one or more environmental triggers are also needed. One of those triggers might be the battery of vaccinations that young children receive. Using regression analysis and controlling for family income and ethnicity, the relationship between the proportion of children who received the recommended vaccines by age 2 years and the prevalence of autism (AUT) or speech or language impairment (SLI) in each U.S. state from 2001 and 2007 was determined. A positive and statistically significant relationship was found: The higher the proportion of children receiving recommended vaccinations, the higher was the prevalence of AUT or SLI. A 1% increase in vaccination was associated with an additional 680 children having AUT or SLI. Neither parental behavior nor access to care affected the results, since vaccination proportions were not significantly related (statistically) to any other disability or to the number of pediatricians in a U.S. state. The results suggest that although mercury has been removed from many vaccines, other culprits may link vaccines to autism. Further study into the relationship between vaccines and autism is warranted.

Autism is a common neurodevelopmental disorder with a significant genetic component. Existing research suggests that multiple genes contribute to autism and that epigenetic effects or gene-gene interactions are likely contributors to autism risk. However, these effects have not yet been identified. Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, has been implicated in autism etiology. Fourteen known autosomal GABA receptor subunit genes were studied to look for the genes associated with autism and their possible interactions. Single-nucleotide polymorphisms (SNPs) were screened in the following genes: GABRG1, GABRA2, GABRA4, and GABRB1 on chromosome 4p12; GABRB2, GABRA6, GABRA1, GABRG2, and GABRP on 5q34-q35.1; GABRR1 and GABRR2 on 6q15; and GABRA5, GABRB3, and GABRG3 on 15q12. Intronic and/or silent mutation SNPs within each gene were analyzed in 470 white families with autism. Initially, SNPs were used in a family-based study for allelic association analysis--with the pedigree disequilibrium test and the family-based association test--and for genotypic and haplotypic association analysis--with the genotype-pedigree disequilibrium test (geno-PDT), the association in the presence of linkage (APL) test, and the haplotype family-based association test. Next, with the use of five refined independent marker sets, extended multifactor-dimensionality reduction (EMDR) analysis was employed to identify the models with locus joint effects, and interaction was further verified by conditional logistic regression. Significant allelic association was found for markers RS1912960 (in GABRA4; P = .01) and HCV9866022 (in GABRR2; P = .04). The geno-PDT found significant genotypic association for HCV8262334 (in GABRA2), RS1912960 and RS2280073 (in GABRA4), and RS2617503 and RS12187676 (in GABRB2). Consistent with the allelic and genotypic association results, EMDR confirmed the main effect at RS1912960 (in GABRA4). EMDR also identified a significant two-locus gene-gene effect model involving RS1912960 in GABRA4 and RS2351299 in GABRB1. Further support for this two-locus model came from both the multilocus geno-PDT and the APL test, which indicated a common genotype and haplotype combination positively associated with disease. Finally, these results were also consistent with the results from the conditional logistic regression, which confirmed the interaction between GABRA4 and GABRB1 (odds ratio = 2.9 for interaction term; P = .002). Through the convergence of all analyses, we conclude that GABRA4 is involved in the etiology of autism and potentially increases autism risk through interaction with GABRB1. These results support the hypothesis that GABA receptor subunit genes are involved in autism, most likely via complex gene-gene interactions.

Autism is a complex disorder characterized by genetic and phenotypic heterogeneity. Analysis of phenotypically homogeneous subtypes has been used to both confirm and narrow potential autism linkage regions such as the chromosomal region 15q11-q13. Increased evidence for linkage in this region had been found in a subgroup of 21 autism families (total families = 94) stratified based on a savant skill factor (SSF) from the Autism Diagnostic Interview, Revised (ADI-R). We examined the savant phenotypic finding in our sample of 91 multiplex autism families. Using two-point parametric analysis in stratification with a cutoff point of a savant skill score of 0.16, our families failed to demonstrate linkage to 15q11-q13. In addition, ordered subset analysis (OSA) using SSF as a covariate also failed to show evidence for linkage. Our findings do not support savant skills as an informative phenotypic subset for linkage in our sample., (Copyright 2005 Wiley-Liss, Inc.)

Autism is a neurodevelopmental disorder characterized by stereotypic and repetitive behavior and interests, together with social and communicative deficiencies. The results of several genomic screens suggest the presence of an autism susceptibility locus on chromosome 19p13.2-q13.4. The apolipoprotein E (APOE) gene on chromosome 19 encodes for a protein, apoE, whose different isoforms (E2, E3, E4) influence neuronal growth. APOE participates in lipid transport and metabolism, repair, growth, and maintenance of axons and myelin during neuronal development. The APOE protein competes with the Reelin protein for VLDL/APOER2 receptor binding. Several studies have reported evidence for an association between autism and the Reelin gene. Based on these data we tested for association between APOE and autism using family-based association methods in a data set of 322 autism families. Three promoter, one intronic, and one 3' UTR single nucleotide polymorphisms (SNPs) in the APOE gene (-491a/t, -427c/t, -219g/t, 113c/g, and 5361c/t) as well as the APOE functional polymorphism (E2, E3, E4) were examined and failed to reveal significant evidence that autism is associated with APOE., (Copyright 2003 Wiley-Liss, Inc.)

In this paper authors present a history and clinical findings of 78 years old man with suspicion of iris melanoma. Malignant melanoma accounts for 70% of cell malignant tumors of the eye. The paper also contains short review of the most important clinical characteristic, diagnostic and treatment of iris melanoma.

This paper presents a case of a 54-year-old patient with unilateral exophthalmos. During the hospitalization basic laboratory investigations, USG, skull X-ray film, NMR of orbits were carried out. The patient was treated with systemic corticosteroids with good response. Inflammatory infiltration and venous stasis are considered to be the cause of exophthalmos. Granulomatous orbital inflammation was detected. The etiology of nonspecific orbital inflammation remains still unknown.

Autistic disorder (AutD) is a complex genetic disease. Available evidence suggests that several genes contribute to the underlying genetic risk for the development of AutD. However, both etiologic heterogeneity and genetic heterogeneity confound the discovery of AutD-susceptibility genes. Chromosome 15q11-q13 has been identified as a strong candidate region on the basis of both the frequent occurrence of chromosomal abnormalities in that region and numerous suggestive linkage and association findings. Ordered-subset analysis (OSA) is a novel statistical method to identify a homogeneous subset of families that contribute to overall linkage at a given chromosomal location and thus to potentially help in the fine mapping and localization of the susceptibility gene within a chromosomal area. For the present analysis, a factor that represents insistence on sameness (IS)--derived from a principal-component factor analysis using data on 221 patients with AutD from the repetitive behaviors/stereotyped patterns domain in the Autism Diagnostic Interview-Revised--was used as a covariate in OSA. Analysis of families sharing high scores on the IS factor increased linkage evidence for the 15q11-q13 region, at the GABRB3 locus, from a LOD score of 1.45 to a LOD score of 4.71. These results narrow our region of interest on chromosome 15 to an area surrounding the gamma-aminobutyric acid-receptor subunit genes, in AutD, and support the hypothesis that the analysis of phenotypic homogeneous subtypes may be a powerful tool for the mapping of disease-susceptibility genes in complex traits.

Autistic disorder is a pervasive neurodevelopmental disorder characterized by deficits in language and social communication, as well as stereotyped patterns of behavior. Peak LOD scores from several genomic screening efforts indicate the presence of an autistic disorder susceptibility locus within the distal long arm of human chromosome 7 (7q31-q35). Wassink et al. [2001: Am J Med Genet 105:406-413] reported that WNT2, located at 7q31, influences genetic risk in autistic disorder. These findings were enhanced when examined in a subset of families with severe language impairment. WNT genes encode secreted growth factor-like proteins that participate in growth regulation, differentiation, and tumorigenesis. We tested for genetic association of two WNT2 variants in an independent data set of 135 singleton and 82 multiplex families. No significant association was found between autistic disorder and the WNT2 genotypes in either the overall data set or in the language-impaired subset of families. However, differences in allele frequencies of the 3' UTR single nucleotide polymorphism between the present population and that of Wassink et al. may account for the inability to detect association between WNT2 and autistic disorder in the present data set. We also screened the two reported autistic disorder mutations previously detected by Wassink et al. We did not identify any activating mutation in the coding region of the WNT2 gene. Thus, we conclude that activating mutations of the WNT2 gene are not a major contributor to the development of autistic disorder in these data., (Copyright 2001 Wiley-Liss, Inc.)

Autistic disorder (AD) is a neurodevelopmental disorder characterized by abnormalities in behavior, communication, and social interactions and functioning. Recently, Cook et al. reported significant linkage disequilibrium with an AD susceptibility locus and a marker, GABRB3 155CA-2, in the gamma-aminobutyric acid(A) (GABA(A)) receptor beta3-subunit gene on chromosome 15q11-q13. This linkage disequilibrium was detected using a multiallelic version of the transmission/disequilibrium test (TDT) in a sample of nuclear families having at least one child with autistic disorder. In an attempt to replicate this finding we tested for linkage disequilibrium with this marker, as well as with three additional markers in and around the GABA(A) receptor beta3-subunit gene, in an independent, clinically comparable set of AD families. Unlike Cook et al., we failed to detect significant linkage disequilibrium between GABRB3 155CA-2 and AD in our sample. We did, however, find suggestive evidence for linkage disequilibrium with a marker, GABRB3, approximately 60 kb beyond the 3' end of beta3-subunit gene. This finding lends support for previous reports implicating the involvement of genes in this region with AD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:43-48, 2000, (Copyright 2000 Wiley-Liss, Inc.)

Genome-wide scans have suggested that a locus on 7q is involved in the etiology of autistic disorder (AD). We have identified an AD family in which three sibs inherited from their mother a paracentric inversion in the chromosome 7 candidate region (inv(7)(q22-q31.2)). Clinically, the two male sibs have AD, while the female sib has expressive language disorder. The mother carries the inversion, but does not express AD. Haplotype data on the family suggest that the chromosomal origin of the inversion was from the children's maternal grandfather. Based on these data, we have genotyped 76 multiplex (>/=2 AD affecteds/family) families for markers in this region of 7q. Two-point linkage analysis yielded a maximum heterogeneity lod score of 1.47 and maximum lod score (MLS) of 1.03 at D7S495. Multipoint MLS and NPL analyses resulted in peak scores of 1.77 at D7S2527 and 2.01 at D7S640. Examination of affected sibpairs revealed significant paternal (P = 0.007), but not maternal (P = 0. 75), identity-by-descent sharing at D7S640. Significant linkage disequilibrium was detected with paternal (P = 0.02), but not maternal (P = 0.15), transmissions at D7S1824 in multiplex and singleton families. There was also evidence for an increase in recombination in the region (D7S1817 to D7S1824) in the AD families versus non-AD families (P = 0.03, sex-averaged; and P = 0.01, sex-specific). These results provide further evidence for the presence of an AD locus on chromosome 7q, as well as provide evidence suggesting that this locus may be paternally expressed., (Copyright 1999 Academic Press.)

We analyzed the interictal [18F]fluoro-2-deoxy-D-glucose positron emission tomography (PET) findings of 17 epileptic patients with neuronal migration disorders (NMDs). Fifteen patients had abnormal PET findings, i.e., focal hypometabolism in 9 patients and displaced metabolic activity of normal gray matter in 6. All 15 patients had magnetic resonance imaging (MRI) abnormalities; however, PET abnormality assisted in the identification of NMDs on MRI in 3 patients. Two patients with negative MRI also had negative PET studies. PET hypometabolism appeared to correlate with severity of neuronal dysgenesis or temporal lobe involvement, or both. Displaced metabolic activity of gray matter is regarded as a unique interictal [18F]fluoro-2-deoxy-D-glucose-PET finding in NMD. This study demonstrates variable metabolic patterns in NMD and that PET may be a useful complement to MRI in the evaluation of NMD.

Brain development in humans is remarkably resistant to permanent damage from protein-energy malnutrition. However, specific nutrients have crucial roles. Iodine deficiency is the most important and widespread nutrient deficiency; it causes endemic cretinism, associated with deaf-mutism and cerebral palsy. Iodine deficiency during pregnancy causes both maternal and fetal hypothyroxinemia, resulting in irreversible impairment of brain development at a critical stage. Neuropathological data place this after 14 wk, perhaps continuing through the third trimester. Gross brain structure, including the gyral pattern of the cerebral cortex, develops normally; the insult affects neuron and dendrite growth. Recent magnetic-resonance-imaging (MRI) images of neurological cretin brains show remarkably normal appearance except for gliotic lesions of the globus pallidus, correlating with the proximal motor rigidity seen clinically. Myxedematous cretinism is paradoxical in showing more severe hypothyroidism and growth failure, yet better intellectual, motor, and hearing function; these observations implicate a second independent factor in its pathogenesis.

We treated four children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with high-dose intravenous immunoglobulin (IVIG). All patients received 400 mg/kg of IVIG a day for 5 days during relapses, and one patient received additional periodic infusions of 400 mg/kg. All patients showed excellent recovery of motor strength following each relapse that was treated with IVIG. Compared with plasmapheresis (which was used to treat relapses earlier), recovery of function with IVIG treatments was similar, and in two patients it was superior, to plasmapheresis. There were no side effects with IVIG treatments as compared with plasmapheresis with which two children had infection of central lines with Staphylococcus epidermidis, one had profuse bleeding from accidental extrusion of a central line, and one had multiple episodes of major venous thromboses. High-dose IVIG was a safe and effective adjunctive therapy for childhood CIDP in these four patients.

The diagnosis and management of headache in children is a challenge to the clinician, covering as it does a wide range of diagnostic possibilities and enlisting a range of skills from neurosurgery and infectious disease to the psychological. The task is best undertaken, as in so many medical problems, by taking careful history and physical examination, including the past history, family history, and life circumstance of the child. After this is done, only in a minority of cases will it be necessary to request a specific special test, such as a CT scan, lumbar puncture or EEG. In those cases where doubt remains after initial careful evaluation or even after special studies have not resolved the question, careful follow up of the child over time, with re-examination as necessary, will allow definitive diagnosis and prevent the physician from missing obscure or in apparent disease.

Three children with known primary brain neoplasms and leptomeningeal disease were evaluated with MR imaging. Two of the patients had medulloblastoma and one had pineoblastoma. The presence of leptomeningeal tumor spread was established by positive CSF cytopathology in conjunction with compatible contrast-enhanced CT findings. Contrast-enhanced CT, nonenhanced MR, and Gd-DTPA-enhanced MR studies were then compared. In two cases, leptomeningeal lesions were seen better with Gd-DTPA-enhanced MR than with contrast-enhanced CT. In all three cases, Gd-DTPA MR imaging revealed lesions that were not identified on noncontrast MR. Gd-DTPA-enhanced MR imaging is useful when searching for intracranial leptomeningeal tumor deposits in pediatric patients at risk for this condition.

Fatal infantile mitochondrial myopathy with lactic acidosis, morphologically abnormal mitochondria, deficient cytochromes aa3 and b, and a Fanconi-like aminoaciduria has been described. We report two infants, second cousins, with a similar fatal mitochondrial disorder, the cytochrome deficiency limited to skeletal muscle in one child and to liver in the other. The first child at 3 months of age had weight loss, hypotonia, external ophthalmoplegia, and a severe lactic acidosis with a high lactate/pyruvate ratio. Electron microscopy of muscle showed marked proliferation of enlarged mitochondria, many containing concentric rings of cristae. In skeletal muscle mitochondria, cytochromes aa3 and b were not detectable but cytochrome cc was found to be normal by spectroscopy. Cytochrome c oxidase activity was less than 1% of normal. Mitochondria from kidney, liver, heart, lung, and brain examined postmortem had normal cytochromes and preserved cytochrome c oxidase activity. The second cousin at 5 months of age had weight loss and hepatomegaly but no systemic lactic acidosis. Liver biopsy showed hepatocytes packed with enlarged mitochondria. The liver mitochondria showed deficient cytochromes aa3 and b postmortem, and cytochrome c oxidase activity was less than 10% of normal. Kidney mitochondria had normal cytochromes. Muscles was not studied. The mitochondrial abnormality in the two cousins presumably is related. Unexplained are the mode of genetic transmission or environmental exposure and the apparent involvement of a single different organ in each child.

Neurological examinations were made of 67 children and adults with congenital iodine-deficiency disorder (endemic cretinism) in four rural villages in highland Ecuador. There was a distinct and readily identifiable pattern of neurological deficits. These included, to varying degrees: deaf-mutism or lesser degrees of bilateral hearing-loss or dysarthria; spasticity, particularly involving the proximal lower extremities; mental deficiency of a characteristic type; and rigidity and bradykinesia. Not all of these elements were found in all cases. Less common features were strabismus, kyphoscoliosis and frontal-lobe signs. There were exceptional cases with hypotonia. In contrast, cerebellar function was largely spared, as were functions of emotion and attention, vegetative and autonomic functions, social interaction, and probably memory, except in the most severely involved.

The 14 & 6 Hz positive spike phenomenon is generally considered a normal variant finding. Our experience prompted this re-evaluation, which consisted of three parts: In children referred for sleep electroencephalograms (EEGs), 100 children with normal EEG and 100 with 14 & 6--the 14 & 6 correlated with behavior disorder and aggression; In 75 children referred for neurological evaluation and EEG because of behavior problems, 52% had 14 & 6 (excluding those with paroxysmal EEGs); and In 57 symptomatic children having prominent 14 & 6, tabulation of symptoms yielded a complex but coherent clinical picture, including disturbances of temper, mood, attention, learning, and sleep. We conclude that 14 & 6 has clinical associations and deserves study.

Between 1969 and 1979 five children were found to have lumbar disc disease and were evaluated for clinically unsuspected thoracic spine abnormalities. Of these five children, two had Scheuermann's disease and one had disc space narrowing associated with Schmorl's nodes. One other had narrowed disc spaces without bony defects, and one had a normal thoracic spine. A unitary concept of childhood lumbar disc disease, Schmorl's nodes and Scheuermann's disease is suggested.

Temporary junctions were observed between developing optic fibers of the chick embryo and were distributed along the entire length of the axons from the cell body to the tip of the growth cone. These junctions were present in all material studied between days E-3 and E-18, the latter being the start of myelin formation of the optic tract. Junctions between adjacent axons were focal in nature and showed a decrease in the size of the intercellular space caused by a close apposition of the plasma membrane. With the experimental techniques used final identification of these junctions could not be made but are thought to be of two types--the gap and occludens junctions. Temporary fasciae adherentes junctions were observed at the end of the axon, between the growth cone and adjacent neural tissue. Speculation was made on the functional role of these temporary junctions.

Pneumoencephalographic findings are described in a group of 18 children who presented to us with a history of retarded language development and autistic behaviour disturbances. None had specific diagnosable neurological diseases nor gross motor disorders. PEG findings included, most prominently, pathological enlargement of the left temporal horn in 15 cases; some cases showed enlargement of both temporal horns or mild variable enlargement of the lateral ventricles, especially the left. Comparisons between infantile autism and recognized patterns of temporal lobe disease (especially Korsakoff syndrome and Kluver-Bucy syndrome) are drawn. We have suggested that medial temporal lobe dysfunction may be a major factor in the pathogenesis of the syndrome of infantile autism.

The etiology of infantile autism is not known. To assess the possible role of familial psychopathology, we investigated a group of autistic subjects subgrouped by level of language function. Family histories were obtained by the family history method. Neurological status was assessed by neurological diagnostic examination and prenatal and perinatal history. The results showed a high incidence of Asperger's syndrome in family members of high-functioning autistic subjects only. The rate of bipolar affective disorder in family members was 4.2%, higher than in the general population; it was significantly higher in families with Asperger's syndrome, suggesting an etiological link between Asperger's syndrome and manic depression. Positive neurological findings were concentrated in the low-functioning subgroup. These findings imply different etiologies for high- versus low-functioning autism, with high-functioning autism related to familial factors, especially Asperger's syndrome.