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Background: Individuals with avoidant/restrictive food intake disorder (ARFID) self-report heightened sensitivity to taste and smell, but neither phenomenon has been systematically explored in the laboratory. We hypothesized that, compared to healthy controls (HC, n = 34), children, adolescents, and adults with full/subthreshold ARFID (n = 100; ages 9 to 23 years) would self-report heightened response to taste/smell stimuli and exhibit stronger bitter taste perception and heightened smell perception in performance-based tasks, and these differences would be especially prominent in those with the ARFID-sensory sensitivity presentation., Method: We measured self-reported sensitivity to taste/smell with the adolescent/adult sensory profile (AASP). We measured performance-based bitter taste perception with the regional taste intensity test (RTIT) and 6-N-propylthiouracil (PROP) test, and olfactory performance with the Sniffin' Sticks test (including the odor threshold, odor detection, and odor identification subscales)., Results: As expected, the ARFID group self-reported heightened response to taste/smell on the AASP, compared to HC, with an especially large effect size in the subset with the ARFID-sensory sensitivity presentation. Contrary to hypotheses, on performance-based measures, neither the ARFID group-nor the ARFID-sensory sensitivity group specifically-demonstrated heightened sensitivity to bitter taste on the RTIT or PROP tests, nor heightened smell perception on the Sniffin' Sticks test., Conclusion: These first laboratory findings in a clinically diagnosed sample of individuals with full/subthreshold ARFID highlight the discrepancy between perceived versus actual sensitivity to taste/smell stimuli. Future research should explore whether this discrepancy can be replicated and therapeutically leveraged to facilitate successful food exposures., (© 2025 Wiley Periodicals LLC.)

Competing Interests: None declared.

By understanding health conditions, impairments, and impact on quality of life for pediatric feeding disorders, assessment and treatment approaches can target multiple levels of health-related domains that improve child health and well-being. The purpose of this study was to characterize medical diagnoses and feeding impairments for children with feeding disorders; examine child quality of life and caregiver impact; and compare quality of life differences between children with feeding disorders and children with other conditions. A cross-sectional study was conducted in the Greater Boston Area, between October 2017 and June 2018. Fifty children with a feeding disorder diagnosis, ages 2-5 years, were enrolled. Demographic and clinical data were abstracted from the electronic health record to characterize medical diagnoses and impairments. Parents completed the Pediatric Quality of Life Generic Core Scales 4.0 (PedsQL) and the Feeding/Swallowing Impact Survey (FS-IS) to understand child quality of life and caregiver impact. We calculated descriptive statistics across the medical diagnosis and impairment groups, and for the surveys. Children presented with heterogeneous medical diagnoses and feeding impairments. We found a mean (SD) total score of 72.82(19.21) on the PedsQL and 2.33(0.89) on the FS-IS demonstrating that children with feeding disorders presented with poor quality of life and their caregivers were negatively impacted by their feeding difficulties. By understanding medical diagnoses, impairments, and quality of life, assessment and treatment methods can be tailored to children's specific needs, as well as address the overall wellbeing of children and their families., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Avoidant/restrictive food intake disorder (ARFID) occurs across the weight spectrum, however research addressing the coexistesnce of ARFID with overweight/obesity (OV/OB) is lacking. We aimed to establish co-occurrence of OV/OB and ARFID and to characterize divergent neurobiological features of ARFID by weight., Method: Youth with full/subthreshold ARFID (12 with healthy weight [HW], 11 with OV/OB) underwent fasting brain fMRI scan while viewing food/non-food images (M age = 16.92 years, 65% female, 87% white). We compared groups on BOLD response to high-calorie foods (HCF) (vs. objects) in food cue processing regions of interest. Following fMRI scanning, we evaluated subjective hunger pre- vs. post-meal. We used a mediation model to explore the association between BMI, brain activation, and hunger., Results: Participants with ARFID and OV/OB demonstrated significant hyperactivation in response to HCF (vs. objects) in the orbitofrontal cortex (OFC) and anterior insula compared with HW participants with ARFID. Mediation analysis yielded a significant indirect effect of group (HW vs. OV/OB) on hunger via OFC activation (effect = 18.39, SE = 11.27, 95% CI [-45.09, -3.00]), suggesting that OFC activation mediates differences in hunger between ARFID participants with HW and OV/OB., Conclusions: Compared to youth with ARFID and HW, those with OV/OB demonstrate hyperactivation of brain areas critical for the reward value of food cues. Postprandial changes in subjective hunger depend on BMI and are mediated by OFC activation to food cues. Whether these neurobiological differences contribute to selective hyperphagia in ARFID presenting with OV/OB and represent potential treatment targets is an important area for future investigation.

Objective: Avoidant/restrictive food intake disorder (ARFID) is characterized by food avoidance or dietary restriction not primarily motivated by body weight/shape concerns. Individuals with ARFID can report early satiation, post-prandial fullness, and high intermeal satiety, but whether these symptoms are related to differences in the biology underlying appetite regulation is unknown. In male and female children and adolescents, we hypothesized that fasting levels of cholecystokinin (CCK), a satiety hormone, would be elevated in participants with ARFID (full or subthreshold) versus healthy controls (HCs). Within the ARFID group, we also explored the relations of CCK with weight status, subjective appetite ratings, and ARFID severity and phenotypes., Methods: A total of 125 participants (83 with full/subthreshold ARFID (per DSM-5 ) and 42 HCs, aged 10.2-23.7 years; 61% female; July 2014-December 2019) underwent fasting blood draws for CCK, completed self-report measures assessing subjective state and trait appetite ratings, and completed a semistructured interview assessing ARFID severity., Results: Fasting CCK was higher in those with full/subthreshold ARFID versus HCs with a large effect ( F 1  = 25.0, P  < .001, η p 2  = 0.17), controlling for age, sex, and body mass index (BMI) percentile. Within the ARFID group, CCK was not significantly related to BMI percentile, subjective appetite ratings, or ARFID characteristic measures., Conclusions: CCK may contribute to etiology and/or maintenance of ARFID, as children and adolescents with heterogeneous presentations of avoidant/restrictive eating appear to show elevated fasting levels compared to healthy youth. Further research is needed to understand relations between CCK and appetite, weight, and eating behavior in ARFID., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

There are currently no evidence-based treatments for adults with avoidant/restrictive food intake disorder (ARFID). The purpose of this study was to evaluate the acceptability, feasibility, and proof-of-concept of cognitive-behavioral therapy for ARFID (CBT-AR) for adults. Males and females (ages 18-55 years) were offered 20-30 outpatient sessions of CBT-AR delivered by one of five therapists. Of 18 eligible adults offered CBT-AR, 15 chose to participate and 14 completed treatment. All patients endorsed high ratings of treatment credibility and expected improvement after the first session, and 93% of completers provided high ratings of satisfaction at the conclusion of treatment. Therapists rated the majority (80%) of patients as "much improved" or "very much improved." Based on intent-to-treat analyses, ARFID severity on the Pica, ARFID, and Rumination Disorder Interview (PARDI) showed a large and significant decrease from pre- to post-treatment; and patients incorporated a mean of 18.0 novel foods. The underweight subgroup ( n = 4) gained an average of 11.38 pounds, showing a large and significant increase in mean BMI from the underweight to the normal-weight range. At post-treatment, 47% of patients no longer met criteria for ARFID. To our knowledge, this is the first prospective treatment study of ARFID in adults. The findings of this study provide preliminary evidence of feasibility, acceptability, and proof-of-concept of CBT-AR for heterogeneous presentations of ARFID in adults. Randomized controlled trials are needed to confirm these findings. ClinicalTrials.gov Identifier: NCT02963220., Competing Interests: Disclosure of interest JJT, KTE, and KRB receive royalties from Cambridge University Press for the sale of their books on ARFID. All other authors declare that they have no competing interest.

Transcranial direct-current stimulation (tDCS) is a non-invasive brain stimulation approach previously shown to enhance memory acquisition, but more studies are needed to elucidate the underlying mechanisms. Here, we examined the effects of anodal tDCS (0.25 mA for 30 min) on the memory performance of male Sprague Dawley rats in the passive avoidance test (PAT) and the associated modifications to the hippocampal proteomes. Results indicate anodal tDCS applied before the acquisition period significantly enhanced memory performance in the PAT. Following PAT, synaptoneurosomes were biochemically purified from the hippocampi of tDCS-treated or sham-treated rats and individual protein abundances were determined by bottom-up liquid chromatography mass spectrometry analysis. Proteomic analysis identified 184 differentially expressed hippocampal proteins when comparing the sham to the tDCS before memory acquisition treatment group. Ingenuity pathway analysis (IPA) showed anodal tDCS before memory acquisition significantly enhanced pathways associated with memory, cognition, learning, transmission, neuritogenesis, and long-term potentiation (LTP). IPA identified significant upstream regulators including bdnf , shank3 , and gsk3b Protein-protein interaction (PPI) and protein sequence similarity (PSS) networks show that glutamate receptor pathways, ion channel activity, memory, learning, cognition, and long-term memory were significantly associated with anodal tDCS. Centrality measures from both networks identified key proteins including dlg , shank , grin , and gria that were significantly modified by tDCS applied before the acquisition period. Together, our results provide descriptive molecular evidence that anodal tDCS enhances memory performance in the PAT by modifying hippocampal synaptic plasticity related proteins., (Copyright © 2019 Jung et al.)

Background: Clinical trials of therapies for spinal muscular atrophy (SMA) that are designed to increase the expression the SMN protein ideally include careful assessment of relevant SMN biomarkers., Objective: In the SMA VALIANT trial, a recent double-blind placebo-controlled crossover study of valproic acid (VPA) in ambulatory adult subjects with SMA, we investigated relevant pharmacodynamic biomarkers in blood samples from SMA subjects by direct longitudinal measurement of histone acetylation and SMN mRNA and protein levels in the presence and absence of VPA treatment., Methods: Thirty-three subjects were randomized to either VPA or placebo for the first 6 months followed by crossover to the opposite arm for an additional 6 months. Outcome measures were compared between the two treatments (VPA and placebo) using a standard crossover analysis., Results: A significant increase in histone H4 acetylation was observed with VPA treatment (p = 0.005). There was insufficient evidence to suggest a treatment effect with either full length or truncated SMN mRNA transcript levels or SMN protein levels., Conclusions: These measures were consistent with the observed lack of change in the primary clinical outcome measure in the VALIANT trial. These results also highlight the added benefit of molecular and pharmacodynamic biomarker measurements in the interpretation of clinical trial outcomes.

White adipose tissue (WAT) is composed of mature adipocytes and a stromal vascular fraction (SVF), which contains a variety of cells, including immune cells that vary among the different WAT depots. Growth hormone (GH) impacts immune function and adiposity in an adipose depot-specific manner. However, its effects on WAT immune cell populations remain unstudied. Bovine GH transgenic (bGH) mice are commonly used to study the in vivo effects of GH. These giant mice have an excess of GH action, impaired glucose metabolism, decreased adiposity, increased lean mass, and a shortened lifespan. Therefore, the purpose of this study was to characterize the WAT depot-specific differences in immune cell populations in the presence of excess GH in vivo. Three WAT depots were assessed: inguinal (sc), epididymal (EPI), and mesenteric (MES). Subcutaneous and MES bGH WAT depots showed a significantly higher number of total SVF cells, yet only MES bGH WAT had higher leukocyte counts compared with control samples. By means of flow cytometry analysis of the SVF, we detected greater macrophage and regulatory T-cell infiltration in sc and MES bGH WAT depots compared with controls. However, no differences were observed in the EPI WAT depot. RNA-sequencing confirmed significant alterations in pathways related to T-cell infiltration and activation in the sc depot with fewer significant changes in the EPI bGH WAT depot. These findings collectively point to a previously unrecognized role for GH in influencing the distribution of WAT immune cell populations in a depot-specific manner.

The aim of the present study was to evaluate oxidative injury in gill pavement cells (GPCs) from fathead minnow (Pimephales promelas) using F2-isoprostane (F2-iP) release as an index of lipid peroxidation. Cells were isolated from pooled gill tissue by collagenase treatment, mechanical sieving, and Percoll density gradient centrifugation. Baseline levels of 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) were measured by incubating GPCs in physiological buffer (10(6) cells/ml) and enzyme immunoassay. After 60 min, the amount of immunoreactive 8-epi-PGF2 alpha (ir8-epi-PGF2 alpha) in control medium ranged from 1,374 to 5,515 pg/ml. Lead nitrate, 0.6 to 120 microM, did not influence ir8-epi-PGF2 alpha release, whereas FeCl3 stimulated release at 500 microM but not at 5 microM. Incubation medium was extracted for acidic lipids and analyzed by liquid chromatography/mass spectrometry/electrospray ionization. A compound in the medium exhibited a retention time on reverse-phase high-performance liquid chromatography nearly identical to that of synthetic 8-epi-PGF2 alpha The mass spectrum taken from the total ion chromatogram from 14.8 to 15.1 min contained a prominent ion at m/z 353, as expected for the molecular ion of 8-epi-PGF2 alpha. Similar results were obtained with tissue subjected to base hydrolysis. Mass spectra of extracted ion chromatograms obtained with gill extracts and authentic standard showed a close correspondence of fragment ions, providing definitive evidence for production and storage of F2-iPs by fish gills. In summary, F2-iP release occurs during lipid peroxidation injury to fish gill epithelium, and its measurement may facilitate aquatic toxicology studies of metallic and nonmetallic contaminants.

The morbidity and mortality of Staphylococcus aureus infections remain high despite antibiotic therapy. To investigate further the observation that penicillins increase the hemolytic activity of staphylococcal cultures, 37 strains were grown in broth with and without subinhibitory nafcillin. Nafcillin stimulated hemolytic activity in nafcillin-susceptible and -resistant isolates. Sterile broth filtrates of nafcillin-associated cultures injected intraperitoneally in mice were more rapidly lethal than filtrates of the same strain grown without nafcillin. Lethality was neutralized by anti-alpha-toxin antisera. DNA-RNA hybridization revealed a nafcillin-associated increase in alpha-toxin mRNA during the postexponential growth phase after the activation of agr. Isolates grown in slightly inhibitory nafcillin concentrations had more alpha-toxin mRNA than did nafcillin-free cultures, whereas agr RNAIII levels were comparable. This suggests that nafcillin-induced alpha-toxin production is not entirely attributable to agr. A supplemental regulatory mechanism may be involved.

Staphylococcal alpha-toxin, a hemolytic exotoxin, can be iodinated using the lactoperoxidase method. 125 I-Labeled alpha-toxin binds to rabbit erythrocytes in an apparently irreversible and highly specific manner. The binding of 125 I-labeled alpha-toxin to erythrocytes of rabbit and human reflects the species specificity of native alpha-toxin. Binding of 125I-labeled alpha-toxin is blocked by the presence of native alpha-toxin, 127I-labeled alpha-toxin, or anti-alpha-toxin antibody. Simultaneous assays of 125I-labeled alpha-toxin binding and leakage of intracellular 86Rb+ suggest that toxin binding and membrane damage are separate, sequential functions. Both the rate and extent of binding are temperature dependent. Rabbit erythrocytes possess 5 X 10(3) binding sites/cell, while human erythrocytes possess no detectable binding sites. Treatment of rabbit erythrocytes with 125I-labeled alpha-toxin appears to decrease the number of unoccupied binding sites. Chaotropic ions can inhibit 125I-labeled alpha-toxin binding and cause bound 125I-labeled alpha-toxin to dissociate from rabbit erythrocyte membranes. Treatment of intact rabbit erythrocytes with pronase reduces both the binding capacity of the cells for 125I-labeled alpha-toxin, and the cells' sensitivity to hemolysis by native alpha-toxin. It is proposed that the primary binding site for alpha-toxin in biomembranes is a surface membrane protein.

Immunological effects of D- and D,L-penicillamine (PA) were studied in efforts to develop assays for synthetic D or D,L analogs and to contribute to the understanding of the mechanism(s) of action of D-PA in rheumatoid arthritis. At the highest doses tolerated by mice, D,L-PA did not significantly inhibit the development of haemagglutinating antibodies in vivo. In studies in vitro with T lymphocytes, D-PA at 1 mM concentration inhibited both concanavalin A- and phytohaemagglutinin-induced transformation as assayed by [3H]thymidine incorporation, but D-PA concentrations of 5 mM were required to inhibit concanavalin A-induced amino acid uptake. No effect of D-PA was observed either on the induction of cytotoxic T cells or on the attack of specifically sensitized T cells on target cells. It is of interest that D-PA at 1 mM concentration did inhibit lipopolysaccharide-induced transformation, which predominately stimulates B lymphocytes. The effects of PA on the induced transformation of T and B cells deserve further attention for studies with analogs of PA.

Recent developments in the area of Staphylococcal alpha-toxin studies are presented which modify the concepts previously held with respect to both biological and physical properties of alpha-toxin. New data concerning the nature of the binding site for alpha-toxin on rabbit erythrocyte membranes and a model to explain the various observed complexes of alpha-toxin and membrane receptor are discussed. Finally, evidence suggesting that Staphylococcal alpha-toxin is a potent demyelinating agent is presented.

Staphylococcal alpha-toxin at 1 microgram and 10 micrograms was injected into the right lateral ventricle of the brain of conscious, unrestrained rats. Clinical behavior and changes in EEG patterns were monitored. Clinical behavior attributed to alpha-toxin intoxication consisted of intermittent periods of stretching, tremors, convulsions and 'barrel rolling'. The EEG patterns, selected from recordings obtained during quiescent periods of behavior, demonstrate focal spiking, with and without recruitment, slow waves, spindling and complex spikes. We conclude that the central nervous system is a critical target for the lethal action of alpha-toxin.

In recent studies we have demonstrated that staphylococcal alpha-toxin can specifically bind to rabbit vagus nerves and cause disruption of myelin sheaths in this peripheral nerve in vitro. We report here that staphylococcal alpha-toxin, incubated in vitro with brain slices or injected intracerebrally into mice, can induce disruption of myelin sheaths in central nervous tissue. Intracerebral injection of alpha-toxin is followed by a characteristic and reproducible syndrome involving ataxia followed by a severe contraction of the limbs on the side contralateral to the injection and a maximal extension of the opposing limbs. At 1.1 micrograms of toxin injected, death occurs within 20 min. Histopathologic examination reveals extensive demyelination with minimal involvement of the axons. It is possible that staphylococcal alpha-toxin may play a role in the etiology of multiple sclerosis.

Staphylococcal alpha-toxin (alpha-toxin) was incubated with 3T3 or SV40-virus transformed mouse 3T3 fibroblasts during 2 hrs at room temperature. This resulted in about a two-fold increase in the hemolytic activity of alpha-toxin toward rabbit RBC. The concentration of alpha-toxin causing 50% hemolysis of rabbit RBC was lowered from about 120 ng/ml to about 65 ng/ml. Release of 86Rb from labeled RBC and isolated rabbit vagus nerves also occured at lower concentrations of alpha-toxin after preincubation with fibroblasts. The enhancement of hemolytic activity of alpha-toxin was still exerted by cultured fibroblasts preheated to 56 degrees C, but fibroblasts exposed to 100 degrees C were ineffective. The hemolytic activity of alpha-toxin toward rabbit RBC was also slightly enhanced by leucine aminopeptidase (5--20 microgram/ml) and aminopeptidase M (30--300 IU/ml).

Iodination of staphylococcal alpha-toxin by the lactoperoxidase method resulted in the maximal incorporation of about 2.5 atoms of iodine per molecule of alpha-toxin. The iodination primarily involved a single tyrosine residue as shown by analysis of both cyanogen bromide and tryptic peptides. Iodination at a level of 1.2 iodine atoms per alpha-toxin molecule led to a dramatic decrease in the hemolytic and lethal activities, although no decrease in the binding of iodinated toxin to rabbit erythrocytes was observed (Cassidy and Harshman (1976), Biochemistry, the following paper in this issue). Monoiodinated alpha-toxin was found to have 15% of the specific hemolytic activity of native alpha-toxin. Incubation of rabbit erythrocytes with iodinated alpha-toxin led to a significant protection from the hemolytic activity of native alpha-toxin added later. The results show the modification of a single unique tyrosyl residue in alpha-toxin permits the resolution of alpha-toxin's biological activities from its cell binding activity.

Chromatography on controlled pore glass in combination with chaotropic buffers makes possible, in a single step, protein purifications of several hundredfold. The new emphasis is on highly selective controllable adsorption. The method is useful for the purification and concentration of proteins from large volumes of complex media and for the purification of proteins that are poorly soluble or tend to aggregate in aqueous solution D-(-)-Beta-Hydroxybutyrate dehydrogenase, a mitochondrial membrane-bound protein, several soluble proteins, and staphylococcal alpha toxin, which can be purified directly from large volumes of culture medium, are used to illustrate the method.

A monoclonal antibody (A-Tox-653.1) selected for its reactivity in a dot immunoblot assay with denatured staphylococcal alpha-toxin has been isolated and its capacity to block the hemolytic and lethal activities of alpha-toxin measured. In addition, 'reactivity with monomer, hexamer, 125I-monoiodinated and CNBr peptides of alpha-toxin was studied. In all cases the reactions of the monoclonal antibody were compared to those obtained with anti-alpha-toxin rabbit hyperimmune serum. We find that while both the monoclonal antibody and the rabbit antiserum react with all forms of alpha-toxin, only the rabbit antiserum blocks hemolytic or lethal activity. Further, the rabbit antiserum reacts with CNBr fragments IV, V ad VII, whereas the monoclonal antibody reacts only with the carboxy terminal CNBr peptide VII. We conclude that, in solution, the carboxy terminal segment of alpha-toxin is relatively free and reaction with the monoclonal antibody neither impedes its binding to the specific receptor on the membrane nor interferes with formation of the hexamer complex.