Infants later diagnosed with autism have lower canonical babbling ratios in the first year of life.

BACKGROUND: Canonical babbling-producing syllables with a mature consonant, full vowel, and smooth transition-is an important developmental milestone that typically occurs in the first year of life. Some studies indicate delayed or reduced canonical babbling in infants at high familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis, but evidence is mixed. More refined characterization of babbling in the first year of life in infants with high likelihood for ASD is needed. METHODS: Vocalizations produced at 6 and 12 months by infants (n = 267) taking part in a longitudinal study were coded for canonical and non-canonical syllables. Infants were categorized as low familial likelihood (LL), high familial likelihood diagnosed with ASD at 24 months (HL-ASD) or not diagnosed (HL-Neg). Language delay was assessed based on 24-month expressive and receptive language scores. Canonical babble ratio (CBR) was calculated by dividing the number of canonical syllables by the number of total syllables. Generalized linear (mixed) models were used to assess the relationship between group membership and CBR, controlling for site, sex, and maternal education. Logistic regression was used to assess whether canonical babbling ratios at 6 and 12 months predict 24-month diagnostic outcome. RESULTS: No diagnostic group differences in CBR were detected at 6 months, but HL-ASD infants produced significantly lower CBR than both the HL-Neg and LL groups at 12 months. HL-Neg infants with language delay also showed reduced CBR at 12 months. Neither 6- nor 12-month CBR was significant predictors of 24-month diagnostic outcome (ASD versus no ASD) in logistic regression. LIMITATIONS: Small numbers of vocalizations produced by infants at 6 months may limit the reliability of CBR estimates. It is not known if results generalize to infants who are not at high familial likelihood, or infants from more diverse racial and socioeconomic backgrounds. CONCLUSIONS: Lower canonical babbling ratios are apparent by the end of the first year of life in ASD regardless of later language delay, but are also observed for infants with later language delay without ASD. Canonical babbling may lack specificity as an early marker when used on its own.

Social Media Changes in Pediatric Residency Programs During COVID-19 Pandemic.

OBJECTIVE: To describe pediatric residency program's virtual presence and opportunities for the 2021 application cycle. METHODS: A total of 202 pediatric residency programs from the Electronic Residency Application Service (ERAS) were reviewed for departmental and residency Twitter, Instagram, and Facebook accounts. These accounts, residency websites, and the Visiting Student Application Service (VSAS) were reviewed for open house opportunities and virtual subinternships. All data were collected from October 12-15, 2020. RESULTS: A total of 261 social media accounts were identified. 123 (61%) programs had at least one account, with 32 (16%) programs having presence on all 3 platforms. 68 (34%) programs established new accounts after March 1, 2020. Instagram appeared most utilized with 106 (52%) programs having accounts. A total of 115 virtual open house opportunities were offered with most offers on Instagram by 61 (30%) programs. Only 2 virtual subinternships were listed on program websites, 2 on Twitter, 1 on Instagram, and 1 on Facebook. CONCLUSIONS: COVID-19 increased the number of social media accounts used by residency programs. Approximately one-third of all accounts were created after March 1, 2020. However, only 16% of residency programs have a presence on all 3 platforms, allowing for more online growth.

A voxel-wise assessment of growth differences in infants developing autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry (TBM) results to obtain voxel-wise growth trajectories. Subjects were grouped by familial risk and clinical diagnosis at 2 years of age. Several regions, including the posterior cingulate gyrus, the cingulum, the fusiform gyrus, and the precentral gyrus, showed a significant effect for the interaction of group and age associated with ASD, either as an increased or a decreased growth rate of the cerebrum. In general, our results showed increased growth rate within white matter with decreased growth rate found mostly in grey matter. Overall, the regions showing increased growth rate were larger and more numerous than those with decreased growth rate. These results detail, at the voxel level, differences in brain growth trajectories in ASD during the first years of life, previously reported in terms of overall brain volume and surface area.

Language delay aggregates in toddler siblings of children with autism spectrum disorder.

BACKGROUND: Language delay is extremely common in children with autism spectrum disorder (ASD), yet it is unclear whether measurable variation in early language is associated with genetic liability for ASD. Assessment of language development in unaffected siblings of children with ASD can inform whether decreased early language ability aggregates with inherited risk for ASD and serves as an ASD endophenotype. METHODS: We implemented two approaches: (1) a meta-analysis of studies comparing language delay, a categorical indicator of language function, and language scores, a continuous metric, in unaffected toddlers at high and low familial risk for ASD, and (2) a parallel analysis of 350 unaffected 24-month-olds in the Infant Brain Imaging Study (IBIS), a prospective study of infants at high and low familial risk for ASD. An advantage of the former was its detection of group differences from pooled data across unique samples; an advantage of the latter was its sensitivity in quantifying early manifestations of language delay while accounting for covariates within a single large sample. RESULTS: Meta-analysis showed that high-risk siblings without ASD (HR-noASD) were three to four times more likely to exhibit language delay versus low-risk siblings without ASD (LR-noASD) and had lower mean receptive and expressive language scores. Analyses of IBIS data corroborated that language delay, specifically receptive language delay, was more frequent in the HR-noASD (n = 235) versus LR-noASD group (n = 115). IBIS language scores were continuously and unimodally distributed, with a pathological shift towards decreased language function in HR-noASD siblings. The elevated inherited risk for ASD was associated with lower receptive and expressive language scores when controlling for sociodemographic factors. For receptive but not expressive language, the effect of risk group remained significant even when controlling for nonverbal cognition. CONCLUSIONS: Greater frequency of language delay and a lower distribution of language scores in high-risk, unaffected toddler-aged siblings support decreased early language ability as an endophenotype for ASD, with a more pronounced effect for receptive versus expressive language. Further characterization of language development is warranted to refine genetic investigations of ASD and to elucidate factors influencing the progression of core autistic traits and related symptoms.

Increased Extra-axial Cerebrospinal Fluid in High-Risk Infants Who Later Develop Autism.

BACKGROUND: We previously reported that infants who developed autism spectrum disorder (ASD) had increased cerebrospinal fluid (CSF) in the subarachnoid space (i.e., extra-axial CSF) from 6 to 24 months of age. We attempted to confirm and extend this finding in a larger independent sample. METHODS: A longitudinal magnetic resonance imaging study of infants at risk for ASD was carried out on 343 infants, who underwent neuroimaging at 6, 12, and 24 months. Of these infants, 221 were at high risk for ASD because of an older sibling with ASD, and 122 were at low risk with no family history of ASD. A total of 47 infants were diagnosed with ASD at 24 months and were compared with 174 high-risk and 122 low-risk infants without ASD. RESULTS: Infants who developed ASD had significantly greater extra-axial CSF volume at 6 months compared with both comparison groups without ASD (18% greater than high-risk infants without ASD; Cohen's d = 0.54). Extra-axial CSF volume remained elevated through 24 months (d = 0.46). Infants with more severe autism symptoms had an even greater volume of extra-axial CSF from 6 to 24 months (24% greater at 6 months, d = 0.70; 15% greater at 24 months, d = 0.70). Extra-axial CSF volume at 6 months predicted which high-risk infants would be diagnosed with ASD at 24 months with an overall accuracy of 69% and corresponding 66% sensitivity and 68% specificity, which was fully cross-validated in a separate sample. CONCLUSIONS: This study confirms and extends previous findings that increased extra-axial CSF is detectable at 6 months in high-risk infants who develop ASD. Future studies will address whether this anomaly is a contributing factor to the etiology of ASD or an early risk marker for ASD.

Network inefficiencies in autism spectrum disorder at 24 months.

Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral symptoms that emerge during the first years of life. Associated with these symptoms are differences in the structure of a wide array of brain regions, and in the connectivity between these regions. However, the use of cohorts with large age variability and participants past the generally recognized age of onset of the defining behaviors means that many of the reported abnormalities may be a result of cascade effects of developmentally earlier deviations. This study assessed differences in connectivity in ASD at the age at which the defining behaviors first become clear. There were 113 24-month-old participants at high risk for ASD, 31 of whom were classified as ASD, and 23 typically developing 24-month-old participants at low risk for ASD. Utilizing diffusion data to obtain measures of the length and strength of connections between anatomical regions, we performed an analysis of network efficiency. Our results showed significantly decreased local and global efficiency over temporal, parietal and occipital lobes in high-risk infants classified as ASD, relative to both low- and high-risk infants not classified as ASD. The frontal lobes showed only a reduction in global efficiency in Broca's area. In addition, these same regions showed an inverse relation between efficiency and symptom severity across the high-risk infants. The results suggest delay or deficits in infants with ASD in the optimization of both local and global aspects of network structure in regions involved in processing auditory and visual stimuli, language and nonlinguistic social stimuli.

Serologically defined Rhipicephalus (Boophilus) microplus larval antigens in BmLF3, a partially pure Sephacryl S-300 fraction of crude larval proteins.

This report is designed to provide additional information regarding larval soluble proteins toward the planned development of a comprehensive database of Rhipicephalus (Boophilus) microplus proteins that elicit a humoral immune response in cattle as a result of natural ectoparasite infestation. Larval proteins of R. microplus are complex and the protein profile is not dominated by any major proteins. This report focuses upon an S-300 Sephacryl (molecular sieve) column fraction, fraction 3 (BmLF3). With the use of SDS-PAGE (without-2ME) and Western blotting with a composite pool of pre- and post-R. microplus larval infestation antiserum BmLF3 was found to contain 7 apparent common ixodid major antigens (207.3, 171.9, 98.0, 86.5, 65.7, 58.9, and 38.0 kDa), those potentially shared with other ixodid species, and 2 apparent R. microplus specific antigens evidenced by low-level antibody binding in crude BmLF3 (149.4 kDa) and HPLC peak 8 of BmLF3 (116.0 kDa). In addition, BmLF3 contains potent inhibitors of trypsin activity. However, these inhibitors of trypsin did not appear to elicit host antibodies as a result of natural ectoparasite exposure, as defined by Western blotting of reduced and denatured trypsin binding proteins purified by affinity chromatography.

Identification and partial purification of serologically defined Boophilus microplus larval antigens by natural ectoparasite exposure.

In an effort to identify life-stage specific Boophilus microplus proteins that elicit a humoral response in cattle, soluble proteins were extracted from 10- to 14-day-old larvae and subsequently fractionated by size-exclusion chromatography and reverse-phase high pressure liquid chromatography. Several antigens were identified by Western blotting as potentially shared with other ixodid tick species since antibodies to these proteins were present in sera of calves not previously exposed to B. microplus. Six putative B. microplus-specific antigens were identified by antibodies in the sera of calves repeatedly exposed to B. microplus larvae. One of the antigens, a 19.1 kDa protein, was used in the development of a diagnostic kELISA for previous exposure to B. microplus. The 19.1 kDa protein did not have tryptic protease activity or inhibit bovine trypsin activity, but appeared to be allergenic in that a partially pure fraction elicited immediate-type hypersensitivity responses in calves previously exposed to B. microplus.

Biochemical diagnosis of organophosphate-insensitivity with neural acetylcholinesterase extracted by sonication from the adult tick synganglion.

A sonication method for the homogeneous extraction of acetylcholinesterase (AChE) from the synganglia of adult ticks is described. The method provides for the extraction of sufficient AChE for multiple assays of enzyme activity in the presence of specific organophosphate (OP) inhibitors for the rapid diagnosis of OP-insensitivity and assignment of homozygous susceptible (SS), heterozygous resistant (RS), and homozygous resistant (RR) genotypes to individual ticks. A single synganglion from adult ticks of either gender and various stages of feeding can successfully be used for AChE extraction. The study presents the results of diagnostic screening of four Boophilus microplus strains for OP-insensitivity. The extraction method and these findings should find utility in support of researchers involved in the mitigation of acaricide resistance in tick populations worldwide, and in particular, the Cattle Fever Tick Surveillance and Quarantine Program maintained by USDA-APHIS/Veterinary Services along the south Texas border that prevents reentry of Boophilus spp. into the United States from endemic populations in Mexico.

Factors that influence the prevalence of acaricide resistance and tick-borne diseases.

This manuscript provides a summary of the results presented at a symposium organized to accumulate information on factors that influence the prevalence of acaricide resistance and tick-borne diseases. This symposium was part of the 19th International Conference of the World Association for the Advancement of Veterinary Parasitology (WAAVP), held in New Orleans, LA, USA, during August 10-14, 2003. Populations of southern cattle ticks, Boophilus microplus, from Mexico have developed resistance to many classes of acaricide including chlorinated hydrocarbons (DDT), pyrethroids, organophosphates, and formamidines (amitraz). Target site mutations are the most common resistance mechanism observed, but there are examples of metabolic mechanisms. In many pyrethroid resistant strains, a single target site mutation on the Na(+) channel confers very high resistance (resistance ratios: >1000x) to both DDT and all pyrethroid acaricides. Acetylcholine esterase affinity for OPs is changed in resistant tick populations. A second mechanism of OP resistance is linked to cytochrome P450 monooxygenase activity. A PCR-based assay to detect a specific sodium channel gene mutation that is associated with resistance to permethrin has been developed. This assay can be performed on individual ticks at any life stage with results available in a few hours. A number of Mexican strains of B. microplus with varying profiles of pesticide resistance have been genotyped using this test. Additionally, a specific metabolic esterase with permethrin-hydrolyzing activity, CzEst9, has been purified and its gene coding region cloned. This esterase has been associated with high resistance to permethrin in one Mexican tick population. Work is continuing to clone specific acetylcholinesterase (AChE) and carboxylesterase genes that appear to be involved in resistance to organophosphates. Our ultimate goal is the design of a battery of DNA- or ELISA-based assays capable of rapidly genotyping individual ticks to obtain a comprehensive profile of their susceptibility to various pesticides. More outbreaks of clinical bovine babesisois and anaplasmosis have been associated with the presence of synthetic pyrethroid (SP) resistance when compared to OP and amidine resistance. This may be the result of differences in the temporal and geographic patterns of resistance development to the different acaricides. If acaricide resistance develops slowly, herd immunity may not be affected. The use of pesticides for the control of pests of cattle other than ticks can affect the incidence of tick resistance and tick-borne diseases. Simple analytical models of tick- and tsetse-borne diseases suggest that reducing the abundance of ticks, by treating cattle with pyrethroids for example, can have a variety of effects on tick-borne diseases. In the worst-case scenario, the models suggest that treating cattle might not only have no impact on trypanosomosis but could increase the incidence of tick-borne disease. In the best-case, treatment could reduce the incidence of both trypanosomosis and tick-borne diseases Surveys of beef and dairy properties in Queensland for which tick resistance to amitraz was known were intended to provide a clear understanding of the economic and management consequences resistance had on their properties. Farmers continued to use amitraz as the major acaricide for tick control after the diagnosis of resistance, although it was supplemented with moxidectin (dairy farms) or fluazuron, macrocyclic lactones or cypermethrin/chlorfenvinphos.

Distribution of horn flies on individual cows as a percentage of the total horn fly population.

Twenty-three mixed-breed herd cows were phenotyped for their ability to serve as a suitable host for Haematobia irritans, the horn fly. Based upon consistent observations within the lower quartile or upper quartile of individual fly counts, four cows were phenotyped as low carriers and five cows were phenotyped as high carriers of horn flies. The cows designated as low carriers consistently carried levels of flies below the economic threshold. However, during a period of fly population explosion, low carriers harbored flies well above the economic threshold. Although the number of flies counted on these low carrying cattle increased as the population increased, the relative percentage of the population that they carried changed very little. A hypothesis is proposed to explain this observation, and future studies are suggested.

Isolation and identification of an esterase from a Mexican strain of Boophilus microplus (Acari: Ixodidae).

A strain of Mexican Boophilus microplus (Cz) collected near Coatzacoalcos, Veracruz, Mexico, exhibits a moderate, but significant, level of permethrin resistance. Unlike other highly permethrin resistant strains, the Cz strain does not have a mutation within the sodium channel gene that results in target-site insensitivity. However, the Cz strain possesses a substantial increase in general and permethrin esterase activity relative to highly permethrin resistant and control strains suggesting the involvement of a metabolic esterase(s) in the expression of permethrin resistance. We report the isolation of a 62.8 kDa protein from Cz strain larvae that we think is the esterase previously reported as Cz EST9. In addition, internal amino acid sequence data obtained from the 62.8 kDa protein suggest that it is the gene product of a previously reported B. microplus carboxylesterase cDNA. We propose that the 62.8 kDa protein (Cz EST9) has permethrin hydrolytic activity and as a result plays an important role in Cz strain resistance to permethrin.

Neural correlates for roughness choice in monkey second somatosensory cortex (SII).

This experiment explored the relationship between neural firing patterns in second somatosensory cortex (SII) and decisions about roughness of tactile gratings. Neural and behavioral data were acquired while monkeys made dichotomous roughness classifications of pairs of gratings that differed in groove width (1.07 vs. 1.90 and 1.42 vs. 2.53 mm). A computer-controlled device delivered the gratings to a single immobilized finger pad. In one set of experiments, three levels of contact force (30, 60, and 90 g) were assigned to these gratings at random. In another set of experiments, three levels of scanning speed (40, 80, and 120 mm/s) were assigned to these gratings at random. Groove width was the intended variable for roughness. Force variation disrupted the monkeys' groove-width (roughness) classifications more than did speed variation. A sample of 32 SII cells showed correlated changes in firing (positive or negative effects of both variables) when groove width and force increased. While these cells were recorded, the monkeys made roughness classification errors, confusing wide groove-width gratings at low force with narrow groove-width gratings at high force. Three-dimensional plots show how some combinations of groove width and force perturbed the monkeys' trial-wise classifications of grating roughness. Psychometric functions show that errors occurred when firing rates failed to distinguish gratings. A possible interpretation is that when asked to classify grating roughness, the monkeys based classifications on the firing rates of a subset of roughness-sensitive cells in SII. Results support human psychophysical data and extend the roughness range of a model of the effects of groove width and force on roughness. One monkey's SII neural sample (21 cells) showed significant correlation between firing rate response functions for groove width and speed (both correlations either positive or negative). Only that monkey showed a statistically significant interaction between groove width and speed on roughness classification performance. This additional finding adds weight to the argument that SII cell firing rates influenced monkey roughness classifications.

Variation in general esterase activity within a population of Haematobia irritans (Diptera: Muscidae).

Control of the horn fly, Hematobia irritans (L.), is generally dependent on chemical insecticides. However, the biology and behavior of the horn fly favors rapid development of insecticide resistance. To prolong the effectiveness of the insecticide option, information is required regarding the mechanisms of insecticide resistance. Metabolic hydrolysis of insecticides by esterases is a detoxification mechanism in many insect species. Measurement of general esterase activity within populations of horn flies may provide a diagnostic tool for resistance management. In this study we evaluated the amount of variation in general esterase activity within female and male horn fly samples from a population that had not been exposed to insecticides for 8 yr. We found considerable variation in general esterase activity within samples of each sex, with females demonstrating the greater variation. The observed variation is thought to be the result of age-structure dynamics within the population. The amount of inherent variation makes it difficult to detect small mean differences between populations, thus limiting the utility of general esterase assays. Thus, effective diagnosis of esterase-mediated resistance mechanisms can only be achieved by the identification of specific detoxification esterases and the design of assays, either biochemical or molecular, for their detection and measurement.

Response patterns in second somatosensory cortex (SII) of awake monkeys to passively applied tactile gratings.

This experiment explored the effects of controlled manipulations of three parameters of tactile gratings, groove width (1.07-2.53 mm), contact force (30-90 g), and scanning speed (40-120 mm/s), on the responses of cells in second somatosensory cortex (SII) of awake monkeys that were performing a groove-width classification task with passively presented stimuli. A previous experiment involving an active touch paradigm demonstrated that macaque SII cells code groove-width and hand-movement parameters in their average firing rates. The present study used a passive-touch protocol to remove somatosensory activation related to hand movements that accompany haptic exploration of surfaces. Monkeys maintained a constant hand position while a robotic device delivered stimulation with tactile gratings to a single stabilized finger pad. Single-unit recordings isolated 216 neurons that were retrospectively assigned to SII on histological criteria. Firing patterns for 86 of these SII cells were characterized in detail, while monkeys classified gratings as rough (1.90 and 2.53 mm groove widths) or smooth (1.07 and 1.42 mm groove widths), with trial-wise random, parametric manipulation of force or speed; the monkeys compared 1.07 versus 1.90 mm and 1.42 versus 2.53 mm in alternating blocks of trials. We studied 33 cells with systematic variation of groove width and force, 49 with groove width and speed, and four with all three variables. Sixty-three cells were sensitive to groove width, 43 to force (effects of random force in speed experiments contributed to N), and 34 to speed. Relatively equal numbers of cells changed mean firing rates as positive or negative functions of increasing groove width, force, and/or speed. Cells typically changed mean firing rates for two or three of the independent variables. Effects of groove width, force, and speed were additive or interactive. The variety of response functions was similar to that found in a prior study of primary somatosensory cortex (SI) that used passive touch. The SII sample population showed correlated changes (both positive and negative) in firing rates with increasing groove width and force and to a lesser degree, with increasing groove width and speed. This correlation is consistent with human psychophysical studies that found increasing groove width and force increase perceived roughness magnitude, and it strengthens the argument for SII's direct involvement in roughness perception.

Myiasis due to Hypoderma lineatum infection mimicking the hypereosinophilic syndrome.

Myiasis is the infestation of live humans with larvae of Diptera (true flies). This report describes a protracted illness caused by infestation with Hypoderma lineatum, resembling the hypereosinophilic syndrome. A 35-year-old man had a 9-month multisystemic illness with pronounced eosinophilia, pleuritis, pericarditis, and myositis. Treatments including glucocorticoids did not alter the disease. Diagnostic studies included computed tomography, 2-dimensional echocardiography, leukocyte count, surgical biopsy of skin and muscle, blood immunoglobulin levels, and blood chemistry. Myiasis was recognized when a worm emerged from the patient's skin; after a second worm emerged, the patient's symptoms disappeared rapidly. Other determinations included IgE and IgG levels specific for H lineatum, Western blot, and immunofluorescence for eosinophil major basic protein; IgG antibodies to H lineatum decreased after emergence of the worms. The patient's symptoms mimicked the hypereosinophilic syndrome but resolved when the myiasis became apparent. Specific serologic analyses can identify infected patients, and ivermectin may be useful as treatment.

Evaluation of horn flies (Diptera: Muscidae) from a pyrethroid susceptible colony for general and permethrin esterase activities.

In this study we describe a nonradioactive single-fly microassay for permethrin hydrolysis. We used this assay with a microplate assay for general esterase activity to evaluate the permethrin hydrolyzing and general esterase activities of aging pyrethroid-susceptible male and female horn flies, Haematobia irritans (L.). We found substantial gender- and age-related differences regarding general esterase activity, permethrin sensitivity, and permethrin hydrolyzing activity within the colony. Extracts of female flies collected 48 h after receiving their first blood meal yielded significantly greater esterase activity than male extracts. Aging female flies were more tolerant of permethrin than were male flies. In addition, a positive correlation was found to exist between the general esterase activity of aging females and their ability to hydrolyze permethrin.

Identification and purification of a 16-kDa allergen from Psoroptes ovis (Acarina: Psoroptidae).

Psoroptes ovis, (Hering), the sheep scab mite, is the causative agent of an allergic dermatitis of sheep and cattle. Recent studies of the host immune response to this ectoparasite have provided information that suggests control may be achieved by immune intervention. A significant effector in protection of the host from clinical lesions is host behavioral grooming. Host grooming is believed to be intensified by a pruritic immediate hypersensitivity response to mite allergens. Knowledge of potential P. ovis allergens is limited. This article reports on the identification and SDS-PAGE continuous elution purification of a 16-kDa polypeptide that elicits immediate type hypersensitivity in calves and has sequence homology with known group II mite allergens, Lep d 2 of Lepidoglyphus destructor (Schrank), and Der f II of Dermatophagoides farinae (Hughes). This P. ovis allergen appears to be a good vaccine candidate for further study and cloning.