American Society of Nephrology Kidney TREKS Program.

In response to decreasing numbers of individuals entering into nephrology fellowships, the American Society of Nephrology launched Kidney TREKS (Tutored Research and Education for Kidney Scholars) to stimulate interest in nephrology among medical students, graduate students, and postdoctoral fellows. The program combines a one-week intensive exposure to kidney physiology with a longitudinal mentorship program at the participants' home institutions. Ten years in, an analysis was conducted to assess its effectiveness. We surveyed participants to assess their opinions regarding nephrology before and after the course and followed them longitudinally to determine their career choices. TREKS applicants who were not selected to participate were used as a comparison group. 381 people participated in the program and 242 completed the survey. After TREKS, both medical students and graduate students showed increased interest in nephrology, with rank scores of 5.6±0.2 pre- to 7.5±0.1 post-course for medical students (mean ± standard deviation, n=189, p=0.001) and 7.3±0.3 to 8.7±0.3 (n=53, p=0.001) for graduate students. In long term follow-up, TREKS medical students chose a nephrology pipeline residency at a higher rate than medical students overall (57% vs. 31%, p=0.01) and TREKS applicants who did not participate (47% vs. 31%, p=0.04). Nephrology fellowship rates for these groups exceeded the general population but did not significantly differ between TREKS participants and applicants. PhD students and postdoctoral TREKS participants had a higher rate of participating in nephrology research compared to TREKS applicants (66% vs. 30%, p=0.01). In summary, the ASN Kidney TREKS program has demonstrated that it can improve interest in nephrology in the short term and increase the number of individuals going into nephrology careers. This long-term effect is most evident in PhD students and postdoctoral participants. Further study is needed to assess the impact of TREKS on enrollment in nephrology fellowship programs.

The Impact of Sex on Cognitive Control in ADHD: Girls Slow to Inhibit, Boys Inhibit Less, and Both Show Higher Response Variability.

OBJECTIVE: To determine whether girls and boys with ADHD show distinct impairments in components of cognitive control across multiple tasks (go/no-go, stop signal, and flanker) and performance metrics (response speed, variability, and errors). METHOD: A total of 300 children, ages 8 to 12 years with ADHD (n = 210, 58 girls) or typically developing (TD; n = 99, 37 girls), completed all tasks. Traditional response measures (e.g., mean and standard deviation of reaction time, inhibition errors, and stop signal reaction time) and ex-Gaussian modeling of reaction times (mu, sigma, and tau) were analyzed. RESULTS: Girls showed intact response inhibition in the context of slower response speed, while boys made more inhibition errors and did not slow their response speed. Both girls and boys with ADHD showed higher response variability and poorer interference control than TD children. CONCLUSION: Girls and boys with ADHD show distinct impairments in cognitive control that may be important for understanding the pathophysiology of ADHD.

Brain glutathione and GABA+ levels in autistic children.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication challenges and repetitive behaviors. Altered neurometabolite levels, including glutathione (GSH) and gamma-aminobutyric acid (GABA), have been proposed as potential contributors to the biology underlying ASD. This study investigated whether cerebral GSH or GABA levels differ between a cohort of children aged 8-12 years with ASD (n = 52) and typically developing children (TDC, n = 49). A comprehensive analysis of GSH and GABA levels in multiple brain regions, including the primary motor cortex (SM1), thalamus (Thal), medial prefrontal cortex (mPFC), and supplementary motor area (SMA), was conducted using single-voxel HERMES MR spectroscopy at 3T. The results revealed no significant differences in cerebral GSH or GABA levels between the ASD and TDC groups across all examined regions. These findings suggest that the concentrations of GSH (an important antioxidant and neuromodulator) and GABA (a major inhibitory neurotransmitter) do not exhibit marked alterations in children with ASD compared to TDC. A statistically significant positive correlation was observed between GABA levels in the SM1 and Thal regions with ADHD inattention scores. No significant correlation was found between metabolite levels and hyper/impulsive scores of ADHD, measures of core ASD symptoms (ADOS-2, SRS-P) or adaptive behavior (ABAS-2). While both GSH and GABA have been implicated in various neurological disorders, the current study provides valuable insights into the specific context of ASD and highlights the need for further research to explore other neurochemical alterations that may contribute to the pathophysiology of this complex disorder.

Sex Differences and Behavioral Associations with Typically Developing Pediatric Regional Cerebellar Gray Matter Volume.

The cerebellum contributes to motor and higher-order control throughout neurodevelopment, with marked growth during childhood. Few studies have investigated differential associations of cerebellar morphometry with function in males and females. The present study examines sex differences in regional cerebellar gray matter volume (GMV) and the moderating effect of sex on the relationship between GMV and motor, cognitive, and emotional functions in a large cohort of typically developing (TD) children. Participants included 371 TD children (123 females, age 8-12 years). A convolutional neural network-based approach was employed for cerebellar parcellation. Volumes were harmonized using ComBat to adjust for hardware-induced variations. Regression analyses examined the effect of sex on GMV and whether sex moderated the relationship between GMV and motor, cognitive, and emotional functions. Males showed larger GMV in right lobules I-V, bilateral lobules VI, crus II/VIIb, and VIII, left lobule X, and vermis regions I-V and VIII-X. Greater motor function correlated with less vermis VI-VII GMV in females. Greater cognitive function correlated with greater left lobule VI GMV in females and less left lobule VI GMV in males. Finally, greater internalizing symptoms correlated with greater bilateral lobule IX GMV in females but less in males. These findings reveal sexually dimorphic patterns of cerebellar structure and associations with motor, cognitive, and emotional functions. Males generally show larger GMV than females. Larger GMV was associated with better cognitive functioning for females and better motor/emotional functioning for males.

Developmental deviation in delay discounting as a transdiagnostic indicator of risk for child psychopathology.

BACKGROUND: The tendency to prefer smaller, immediate rewards over larger, delayed rewards is known as delay discounting (DD). Developmental deviations in DD may be key in characterizing psychiatric and neurodevelopmental disorders. Recent work empirically supported DD as a transdiagnostic process in various psychiatric disorders. Yet, there is a lack of research relating developmental changes in DD from mid-childhood to adolescence to psychiatric and neurodevelopmental disorders. Additionally, examining the interplay between socioeconomic status/total household income (THI) and psychiatric symptoms is vital for a more comprehensive understanding of pediatric pathology and its complex relationship with DD. METHODS: The current study addresses this gap in a robust psychiatric sample of 1843 children and adolescents aged 5-18 (M = 10.6, SD = 3.17; 1,219 males, 624 females). General additive models (GAMs) characterized the shape of age-related changes in monetary and food reward discounting for nine psychiatric disorders compared with neurotypical youth (NT; n = 123). Over 40% of our sample possessed a minimum of at least three psychiatric or neurodevelopmental disorders. We used bootstrap-enhanced Louvain community detection to map DD-related comorbidity patterns. We derived five subtypes based on diagnostic categories present in our sample. DD patterns were then compared across each of the subtypes. Further, we evaluated the effect of cognitive ability, emotional and behavioral problems, and THI in relation to DD across development. RESULTS: Higher discounting was found in six of the nine disorders we examined relative to NT. DD was consistently elevated across development for most disorders, except for depressive disorders, with age-specific DD differences compared with NTs. Community detection analyses revealed that one comorbidity subtype consisting primarily of Attention-Deficit/Hyperactivity Disorder (ADHD) Combined Presentation and anxiety disorders displayed the highest overall emotional/behavioral problems and greater DD for the food reward. An additional subtype composed mainly of ADHD, predominantly Inattentive Presentation, learning, and developmental disorders, showed the greatest DD for food and monetary rewards compared with the other subtypes. This subtype had deficits in reasoning ability, evidenced by low cognitive and academic achievement performance. For this ADHD-I and developmental disorders subtype, THI was related to DD across the age span such that participants with high THI showed no differences in DD compared with NTs. In contrast, participants with low THI showed significantly worse DD trajectories than all others. Our results also support prior work showing that DD follows nonlinear developmental patterns. CONCLUSIONS: We demonstrate preliminary evidence for DD as a transdiagnostic marker of psychiatric and neurodevelopmental disorders in children and adolescents. Comorbidity subtypes illuminate DD heterogeneity, facilitating the identification of high-risk individuals. Importantly, our findings revealed a marked link between DD and intellectual reasoning, with children from lower-income households exhibiting lower reasoning skills and heightened DD. These observations underscore the potential consequences of compromised self-regulation in economically disadvantaged individuals with these disorders, emphasizing the need for tailored interventions and further research to support improved outcomes.

The times they are K+-changin': bringing the potassium curriculum out of the 20th century.

PURPOSE OF REVIEW: Although most of the current medical education literature has focused on teaching strategies, little attention has been devoted to selecting appropriate course content. Despite elegant descriptions of physiologic mechanisms in recent decades, medical school curricula and students continue to rely on outdated textbooks and certification examination study aids composed to fit an antiquated exam blueprint. RECENT FINDINGS: Advances in our understanding of potassium physiology offer multiple examples of key concepts that deserve to be included in the modern-day renal physiology curriculum, including the relationship of potassium to blood pressure and the potassium 'switch', the aldosterone paradox, and novel pharmacologic agents that target dietary potassium absorption and potassium handling in the kidney. SUMMARY: Key advances in our understanding and application of renal physiology to patient care have not been readily integrated into the nephrology curriculum of medical students. Difficult questions remain regarding when new concepts are sufficiently established to be introduced to medical students in the preclinical years.

Perceptual alterations in the relationship between sensory reactivity, intolerance of uncertainty, and anxiety in autistic children with and without ADHD.

Sensory differences and anxiety disorders are highly prevalent in autistic individuals with and without ADHD. Studies have shown that sensory differences and anxiety are associated and that intolerance of uncertainty (IU) plays an important role in this relationship. However, it is unclear as to how different levels of the sensory processing pathway (i.e., perceptual, affective, or behavioral) contribute. Here, we used psychophysics to assess how alterations in tactile perception contribute to questionnaire measures of sensory reactivity, IU, and anxiety. Thirty-eight autistic children (aged 8-12 years; 27 with co-occurring ADHD) were included. Consistent with previous findings, mediation analyses showed that child-reported IU fully mediated an association between parent-reported sensory reactivity and parent-reported anxiety and that anxiety partially mediated an association between sensory reactivity and IU. Of the vibrotactile thresholds, only simultaneous frequency discrimination (SFD) thresholds correlated with sensory reactivity. Interestingly, we found that sensory reactivity fully mediated an association between SFD threshold and anxiety, and between SFD threshold and IU. Taken together, those findings suggest a mechanistic pathway whereby tactile perceptual alterations contribute to sensory reactivity at the affective level, leading in turn to increased IU and anxiety. This stepwise association can inform potential interventions for IU and anxiety in autism.

Brain Glutathione and GABA+ levels in autistic children.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication challenges and repetitive behaviors. Altered neurometabolite levels, including glutathione (GSH) and gamma-aminobutyric acid (GABA), have been proposed as potential contributors to the biology underlying ASD. This study investigated whether cerebral GSH or GABA levels differ between a large cohort of children aged 8-12 years with ASD (n=52) and typically developing children (TDC, n=49). A comprehensive analysis of GSH and GABA levels in multiple brain regions, including the primary motor cortex (SM1), thalamus (Thal), medial prefrontal cortex (mPFC), and supplementary motor area (SMA), was conducted using single-voxel HERMES MR spectroscopy at 3T. The results revealed no significant differences in cerebral GSH or GABA levels between the ASD and TDC groups across all examined regions. These findings suggest that the concentrations of GSH (an important antioxidant and neuromodulator) and GABA (a major inhibitory neurotransmitter) do not exhibit marked alterations in children with ASD compared to TDC. A statistically significant positive correlation was observed between GABA levels in the SM1 and Thal regions with ADHD inattention scores. No significant correlation was found between metabolite levels and hyper/impulsive scores of ADHD, measures of core ASD symptoms (ADOS-2, SRS-P) or adaptive behavior (ABAS-2). While both GSH and GABA have been implicated in various neurological disorders, the current study provides valuable insights into the specific context of ASD and highlights the need for further research to explore other neurochemical alterations that may contribute to the pathophysiology of this complex disorder.

ADHD-related sex differences in frontal lobe white matter microstructure and associations with response control under conditions of varying cognitive load and motivational contingencies.

Children with attention-deficit/hyperactivity disorder (ADHD) demonstrate reduced response inhibition, increased response time variability, and atypical frontal lobe white matter microstructure with emerging evidence of sex differences. This study aims to examine whether frontal lobe white matter microstructure is differentially impacted in ADHD by sex and whether this relates to Go/No-Go (GNG) task performance. Diffusion tensor imaging (DTI) from 187 children (8-12 years), including ADHD (n = 94) and typically developing controls (TD; n = 93). Participants completed three GNG tasks with varying cognitive demands and incentives (standard, cognitive, and motivational). Fractional anisotropy (FA) was examined as an index of white matter microstructure within bilateral frontal lobe regions of interest. Children with ADHD showed reduced FA in primary motor (M1) and supplementary motor area (SMA) regardless of sex. Sex-based dissociation for the effect of diagnosis was observed in medial orbitofrontal cortex (mOFC), with higher FA in girls with ADHD and lower FA in boys with ADHD. Both diagnosis and sex contributed to performance on measures of response inhibition and reaction time (RT) variability, with all children with ADHD demonstrating poorer performance on all GNG tasks, but boys with ADHD demonstrating more impulsivity on standard and motivational behavioral paradigms compared to girls with ADHD. Analyses revealed associations between reduced FA in M1, SMA, and mOFC and increased response inhibition and RT variability with some sex-based differences. These findings provide novel insights regarding the brain basis of ADHD and associated impairments in response inhibition and RT variability, and contribute to our understanding of sexual dimorphic behavioral outcomes.

Fluent contextual reading is associated with greater synchronization of the visual and auditory networks, fluent reading and better speed of processing in children with dyslexia.

The asynchrony theory of dyslexia postulates weaker visual (orthographical processing) and auditory (phonological processing) network synchrony in dyslexic readers. The weaker visual-auditory network synchronization is suggested to contribute to slow processing speed, which supports cognitive control, contributing to single-word reading difficulty and lower reading fluency. The current study aims to determine the neurobiological signature for this theory and to examine if prompting enhanced reading speed through deleted text is associated with a greater synchronization of functional connectivity of the visual and auditory networks in children with dyslexia and typical readers (TRs). We further aimed to determine if the change in visual-auditory connectivity prompted by deleted text is associated with reading fluency and processing speed abilities. Nineteen children with dyslexia and 21 typical readers ages 8-12 years old participated in a fMRI under two types of reading conditions: a still text condition and deleted text condition, in which letters was sequentially deleted from the screen. Effects of diagnostic group and condition on functional connectivity (FC) of visual and auditory networks were examined. Results revealed a significant overall effect of condition with a marginally significant Group × Condition interaction, such that as compared with TRs, children with dyslexia showed a significantly greater increase in visual-auditory FC between the still and deleted text conditions. Additionally, for children with dyslexia, this FC increase was significantly correlated with better reading fluency and verbal/nonverbal processing speed. These results support a relationship between the synchronization of the visual and auditory networks, fluent reading and increased speed of processing abilities in children with dyslexia, which can help guide fluency-based intervention strategies.

Acid Base Disorders in Cirrhosis.

Metabolic and respiratory acid-base disorders are common in individuals with liver disease and cirrhosis. The most common disorder is respiratory alkalosis, which may be related to dyspnea or respiratory stimulation. Primary metabolic disorders are less common. Although the liver plays a role in metabolism of amino acids and generation of acid from dietary sources, it does not play a role in the regulation of pH. Instead, metabolic disorders may arise from alterations in normal metabolism or from medications, particularly diuretics and osmotic laxatives, used in the treatment of these complex patients. Understanding the mechanistic underpinnings of these disorders can aid in the management of individuals with liver disease in the hospital and in outpatient settings.

Examining the latent structure and correlates of sensory reactivity in autism: a multi-site integrative data analysis by the autism sensory research consortium.

BACKGROUND: Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population. METHODS: Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a "general response pattern" factor for each supra-modal construct and determine the added value of "modality-specific response pattern" scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO, and SEEK (sub)constructs. RESULTS: All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses supported the validity of a supra-modal HYPER construct (ωH = .800) but not a supra-modal HYPO construct (ωH = .653), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (ωH = .800; 4/7 modalities). Modality-specific subscales demonstrated significant added value for all response patterns. Meta-analytic correlations varied by construct, although sensory features tended to correlate most with other domains of core autism features and co-occurring psychiatric symptoms (with general HYPER and speech HYPO demonstrating the largest numbers of practically significant correlations). LIMITATIONS: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to caregiver report of observable behaviors and excluded multisensory items that reflect many "real-world" sensory experiences. CONCLUSION: Of the three sensory response patterns, only HYPER demonstrated sufficient evidence for valid interpretation at the supra-modal level, whereas supra-modal HYPO/SEEK constructs demonstrated substantial psychometric limitations. For clinicians and researchers seeking to characterize sensory reactivity in autism, modality-specific response pattern scores may represent viable alternatives that overcome many of these limitations.

Identifying the Toxidrome of Ivermectin Toxicity.

Ivermectin is an antiparasitic drug that has been used as an alternative for prophylaxis and treatment of COVID-19 infection. The adverse effects from supratherapeutic doses of ivermectin can include non-neurological and neurological symptoms. In this study, we report the case of a 52-year-old Filipino male with newly diagnosed diabetes mellitus who developed a subacute history of fever, cough, and generalized weakness, causing him to self-medicate with supratherapeutic doses of ivermectin and thereafter subsequently developed a decrease in sensorium, restlessness, and complex visual hallucinations. Significant laboratory examinations showed hyperglycemia, mild hyponatremia, positive SARS-CoV2 reverse transcriptase polymerase chain reaction test, and bilateral pneumonia on chest radiograph. He was subsequently started on antibiotics, a high-flow nasal cannula, and given two doses of activated charcoal. During the first 24 hours of hospital admission, there was a significant improvement in the patient's sensorium with a resolution of restlessness and visual hallucinations. During the rest of the hospitalization, his respiratory symptoms improved, and he was subsequently discharged. Clinical outcome in our patient after administration of activated charcoal and completion of antibiotics showed an overall improvement in symptoms and without any neurologic sequelae.

Sex differences in atypical fronto-subcortical structural connectivity among children with attention-deficit/hyperactivity disorder: Associations with delay discounting.

PURPOSE: Atypical fronto-subcortical neural circuitry has been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), including connections between prefrontal cortical regions involved in top-down cognitive control and subcortical limbic structures (striatum and amygdala) involved in bottom-up reward and emotional processing. The integrity of fronto-subcortical connections may also relate to interindividual variability in delay discounting, or a preference for smaller, immediate over larger, delayed rewards, which is associated with ADHD, with recent evidence of ADHD-related sex differences. METHODS: We applied diffusion tensor imaging to compare the integrity of the white matter connections within fronto-subcortical tracts among 187 8-12 year-old children either with ADHD ((n = 106; 29 girls) or typically developing (TD) controls ((n = 81; 28 girls). Analyses focused on diagnostic group differences in fractional anisotropy (FA) within fronto-subcortical circuitry implicated in delay discounting, connecting subregions of the striatum (dorsal executive and ventral limbic areas) and amygdala with prefrontal regions of interest (dorsolateral [dlPFC], orbitofrontal [OFC] and anterior cingulate cortex [ACC]), and associations with two behavioral assessments of delay discounting. RESULTS: Children with ADHD showed reduced FA in tracts connecting OFC with ventral striatum, regardless of sex, whereas reduced FA in the OFC-amygdala and ventral ACC-amygdala tracts were specific to boys with ADHD. Across diagnostic groups and sex, reduced FA in the dorsal ACC-executive striatum tract correlated with greater game time delay discounting. CONCLUSIONS: These results suggest a potential neurobiological substrate of heightened delay discounting in children with ADHD and support the need for additional studies including larger sample sizes of girls with ADHD to further elucidate ADHD-related sex differences in these relationships.

ADHD-related sex differences in emotional symptoms across development.

To investigate developmental changes in emotion dysregulation (ED) and associated symptoms of emotional lability, irritability, anxiety, and depression, among girls and boys with and without ADHD from childhood through adolescence. Data were collected from a sample of 8-18-year-old children with (n = 264; 76 girls) and without (n = 153; 56 girls) ADHD, with multiple time-points from a subsample of participants (n = 121). Parents and youth completed rating scales assessing child ED, emotional lability, irritability, anxiety, and depression. Mixed effects models were employed to examine effects and interactions of diagnosis, sex [biological sex assigned at birth], age among boys and girls with and without ADHD. Mixed effects analyses showed sexually dimorphic developmental patterns between boys and girls, such that boys with ADHD showed a greater reduction in ED, irritability, and anxiety with age compared to girls with ADHD, whose symptom levels remained elevated relative to TD girls. Depressive symptoms were persistently elevated among girls with ADHD compared to boys with ADHD, whose symptoms decreased with age, relative to same-sex TD peers. While both boys and girls with ADHD showed higher levels of ED during childhood (compared to their sex-matched TD peers), mixed effects analyses revealed substantial sexually dimorphic patterns of emotional symptom change during adolescence: Boys with ADHD showed robust improvements in emotional symptoms from childhood to adolescence while girls with ADHD continued to show high and/or increased levels of ED, emotional lability, irritability, anxiety and depression.

Biomarkers of tic severity in children with Tourette syndrome: Motor cortex inhibition measured with transcranial magnetic stimulation.

AIM: To compare transcranial magnetic stimulation (TMS)-derived measures of primary motor cortex (M1) physiology between children with and without Tourette syndrome, and to dimensionally analyze TMS measures with Tourette syndrome-related symptom severity. METHOD: We used a cross-sectional experimental design. Sixty 8- to 12-year-old children participated (30 with Tourette syndrome: three females, mean age 10 years 10 months, standard deviation [SD] 1 year 3 months; 30 typically developing children: seven females, mean age 10 years 7 months, SD 1 year 3 months). In the group with Tourette syndrome, 15 (one female, mean age 10 years 11 months, SD 1 year 3 months) had comorbid attention-deficit/hyperactivity disorder (ADHD), rated with the Conners, Third Edition and the parent-reported ADHD rating scales. Tic severity was rated with the Yale Global Tic Severity Scale and urge severity with the Individualized Premonitory Urge for Tics Scale. M1 short-interval cortical inhibition (SICI) and intracortical facilitation were compared between diagnostic groups and, within the group with Tourette syndrome, correlated with symptom severity using linear mixed-effects models for repeated measures. RESULTS: Accounting for ADHD, we found no difference in SICI or intracortical facilitation in those with Tourette syndrome versus typically developing children (p > 0.1). In the group with Tourette syndrome, reduced M1 SICI predicted greater total (p = 0.012) and global (p = 0.002) tic severity. There were no associations with urge severity (p > 0.5). INTERPRETATION: Reduced M1 SICI is robustly associated with increased tic, but not urge, severity. WHAT THIS PAPER ADDS: Increased tic severity is associated with reduced motor cortex short-interval cortical inhibition (SICI). Children with Tourette syndrome with increased urge severity also show increased tic severity. However, reduced motor cortex SICI is associated with tic, but not urge, severity.