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Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel treatments are urgently needed to improve clinical outcomes. In this open-label feasibility study, 10 adult female participants (mean body mass index 19.7 kg m -2 ; s.d. 3.7) who met Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM-5) criteria for AN or pAN (partial remission) were recruited to a study conducted at an academic clinical research institute. Participants received a single 25-mg dose of synthetic psilocybin in conjunction with psychological support. The primary aim was to assess safety, tolerability and feasibility at post-treatment by incidences and occurrences of adverse events (AEs) and clinically significant changes in electrocardiogram (ECG), laboratory tests, vital signs and suicidality. No clinically significant changes were observed in ECG, vital signs or suicidality. Two participants developed asymptomatic hypoglycemia at post-treatment, which resolved within 24 h. No other clinically significant changes were observed in laboratory values. All AEs were mild and transient in nature. Participants' qualitative perceptions suggest that the treatment was acceptable for most participants. Results suggest that psilocybin therapy is safe, tolerable and acceptable for female AN, which is a promising finding given physiological dangers and problems with treatment engagement. ClinicalTrials.gov identifier NCT04661514. Appeared originally in Nat Med 2023; 29:1947-1953., (Copyright © 2024 by the American Psychiatric Association.)

Background: Appetite suppression and weight loss are established potential side effects of most medications for attention deficit/hyperactivity disorder (ADHD). These side effects may be especially problematic when using stimulants to treat ADHD in the context of a restrictive eating disorder, such as avoidant restrictive food intake disorder (ARFID), although these diagnoses are often comorbid in children. This paper presents a combined approach to treating ADHD comorbid with ARFID using stimulant medication and behavior management within a partial hospitalization program (PHP) and intensive outpatient program (IOP)for eating disorders. The aim of this paper is to determine if the continued or new use of stimulant medication allows for adequate weight restoration by reviewing a series of cases receiving the combined treatment., Case Presentations: Consecutive patients with a historical or new diagnosis of ADHD when presenting for treatment for ARFID were included in this case series. This series included 10 patients (8 male, 2 female) who received pharmacotherapy using stimulants and behavior management interventions involving structured mealtimes and contingency management. All treatment occurred within the context of a PHP/IOP for childhood eating disorders. All youth were able to effectively continue on stimulant medication, show clinical benefit in core ADHD symptoms, and able to gradually restore weight. In all cases, stimulant medications were not discontinued, but in some cases, doses were optimized (increased or decreased), switched to a different stimulant, or augmented with non-ADHD medication, such as mirtazapine, to support the management of ADHD while concurrently assisting in weight gain as necessary for the treatment of ARFID. Only one patient was newly started on a stimulant medication; as this was near the end of her treatment stay, limited conclusions can be drawn from this case., Conclusions: These findings support the use of pharmacotherapy, including continuing stimulant medication, when combined with behavior management strategies as a potentially effective treatment approach for ADHD in youth with ARFID in the PHP/IOP setting. Future studies using more rigorous methodology, longer follow-up times, and within other treatment settings are needed., (© 2023. The Author(s).)

Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel treatments are urgently needed to improve clinical outcomes. In this open-label feasibility study, 10 adult female participants (mean body mass index 19.7 kg m - 2 ; s.d. 3.7) who met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AN or pAN (partial remission) were recruited to a study conducted at an academic clinical research institute. Participants received a single 25-mg dose of synthetic psilocybin in conjunction with psychological support. The primary aim was to assess safety, tolerability and feasibility at post-treatment by incidences and occurrences of adverse events (AEs) and clinically significant changes in electrocardiogram (ECG), laboratory tests, vital signs and suicidality. No clinically significant changes were observed in ECG, vital signs or suicidality. Two participants developed asymptomatic hypoglycemia at post-treatment, which resolved within 24 h. No other clinically significant changes were observed in laboratory values. All AEs were mild and transient in nature. Participants' qualitative perceptions suggest that the treatment was acceptable for most participants. Results suggest that psilocybin therapy is safe, tolerable and acceptable for female AN, which is a promising finding given physiological dangers and problems with treatment engagement. ClinicalTrials.gov identifier NCT04661514 ., (© 2023. The Author(s).)

While neuroimaging studies typically collapse data from many subjects, brain functional organization varies between individuals, and characterizing this variability is crucial for relating brain activity to behavioral phenotypes. Rest has become the default state for probing individual differences, chiefly because it is easy to acquire and a supposed neutral backdrop. However, the assumption that rest is the optimal condition for individual differences research is largely untested. In fact, other brain states may afford a better ratio of within- to between-subject variability, facilitating biomarker discovery. Depending on the trait or behavior under study, certain tasks may bring out meaningful idiosyncrasies across subjects, essentially enhancing the individual signal in networks of interest beyond what can be measured at rest. Here, we review theoretical considerations and existing work on how brain state influences individual differences in functional connectivity, present some preliminary analyses of within- and between-subject variability across conditions using data from the Human Connectome Project, and outline questions for future study., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Retrospective studies have associated perioperative regional anesthesia/analgesia during mastectomy for breast cancer with a decreased incidence of cancer recurrence. However, to date, no prospective data from a randomized controlled trial have been reported. In a previous study we found that extending a single-injection paravertebral block with a multiple-day perineural local anesthetic infusion improves analgesia. This follow-up study investigates the rates of cancer recurrence for the single-injection and multiple-day infusion treatments., Methods: Patients undergoing unilateral (n = 24) or bilateral mastectomy (n = 36) were included in the study. All patients had been diagnosed with breast cancer or tumor in situ, except for six patients who were receiving prophylactic bilateral mastectomy and were excluded from analyses. Patients received unilateral or bilateral single-injection thoracic paravertebral block(s) corresponding to their surgical site(s) with ropivacaine and perineural catheter(s). Subsequently, patients were randomized to receive either ropivacaine 0.4% (n = 30) or normal saline (n = 30) via their catheter(s) until catheter removal on postoperative day 3. Cancer recurrence from the date of surgery until at least 2 years post surgery was investigated via chart review., Results: Five of the 54 (9.2%) patients experienced a cancer recurrence following mastectomy-3 of 26 (11.5%) of the patients with perineural ropivacaine and 2 of 28 (7.1%) of the patients with perineural saline., Conclusions: This pilot study found no evidence that extending a single-injection paravertebral block with a multi-day perineural local anesthetic infusion decreases the risk of post-mastectomy cancer recurrence. However, due to the small sample size of this investigation, further research is needed to draw definitive conclusions.

Combined scientific advances in pharmaceutical agents, perineural blocks, and pump delivery capabilities such as those used with continuous peripheral nerve blocks have demonstrated advantages in pain management for patients undergoing joint arthroplasty. This report documents the incidence of falls increased after the implementation of a continuous peripheral nerve block program for patients undergoing knee and hip arthroplasty in an academic medical center.

The membrane cytoskeletal component dystrophin and its associated glycoproteins play a central role in the molecular pathogenesis of several muscular dystrophies, i.e. Duchenne/Becker muscular dystrophy, congenital muscular dystrophy and various forms of limb-girdle muscular dystrophy. Although the most frequent of these disorders, Duchenne muscular dystrophy, is mainly recognized as a disease of skeletal muscle fibers, pathophysiological changes also involve the heart and diaphragm, as well as the peripheral and central nervous system. Thus current research efforts into the elucidation of the molecular mechanisms underlying these genetic diseases are not only directed towards studying skeletal muscle necrosis but also investigate abnormalities of heart and brain dystrophin-glycoprotein complexes in cardiomyopathy and brain deficiencies associated with muscular dystrophy. Furthermore, many isoforms of dystrophin and dystrophin-associated components have been identified in various non-muscle tissues and their function(s) are mostly unknown. With respect to skeletal muscle fibers, the characterization of new dystrophin-associated proteins, such as dystrobrevin, sarcospan and the syntrophins, led to a modified model of the spatial configuration of the dystrophin-glycoprotein complex. However, it is generally accepted now that beta-dystroglycan forms the plasmalemma-spanning linkage between dystrophin and the laminin-binding protein alpha-dystroglycan and that this complex is associated with the sarcoglycan subcomplex of sarcolemmal glycoproteins.

Abnormalities in the muscle dystrophin-glycoprotein complex are implicated in the molecular pathogenesis of various neuromuscular disorders. Weakening of the trans-sarcolemmal linkage between the actin membrane-cytoskeleton and the extracellular matrix appears to trigger destabilization of the muscle cell periphery. In addition to muscular weakness, one-third of patients suffering from Duchenne muscular dystrophy exhibit mental retardation. Since little is known about the pathophysiology of brain abnormalities in these patients, we investigated the fate of the most abundant dystrophin-associated protein, beta-dystroglycan, in the central nervous system. It was found to be present throughout all normal brain regions studied. In contrast, this glycoprotein was greatly reduced in brain microsomes derived from Duchenne specimens, while it is of normal abundance in the brain from the dystrophic animal model mdx. Deficiency in brain beta-dystroglycan might render nervous tissue more susceptible to cellular disturbances and this may result in cognitive impairment in some Duchenne patients.

The surface component beta-dystroglycan is a member of the dystrophin-glycoprotein complex providing a trans-sarcolemmal linkage between the actin membrane cytoskeleton and the extracellular matrix component laminin-alpha2. Although abnormalities in this complex are involved in the pathophysiology of various neuromuscular disorders, little is known about the organization of dystrophin-associated glycoproteins in diaphragm and brain. We therefore investigated the oligomerization of beta-dystroglycan and its connection with the most abundant dystrophin homologues in these two tissues. Employing detergent solubilization and alkaline extraction procedures of native membranes, it was confirmed that beta-dystroglycan behaves like an integral surface molecule as predicted by its cDNA sequence. Immunoblot analysis following chemical crosslinking of native membranes showed that beta-dystroglycan has a tendency to form high-molecular-mass complexes. Within these crosslinkable complexes, immuno-reactive overlaps were observed between beta-dystroglycan, alpha-dystroglycan, laminin and 427 kDa dystrophin in diaphragm and skeletal muscle. In synaptosomes, the major brain dystrophin isoform Dp116 also exhibited an immuno-reactive overlap with members of the dystroglycan complex. These findings demonstrate that beta-dystroglycan does not exist as a monomer in native membranes and imply that certain dystrophin isoforms and dystrophin-associated components interact with this surface protein in diaphragm and brain as has been previously shown for skeletal and heart muscle., (Copyright 1998 Elsevier Science B.V.)

The membrane cytoskeletal component dystrophin, which is the protein product of the human Duchenne muscular dystrophy gene, exists in manifold isoforms. Using immunoblot analysis with an antibody to the carboxy-terminal domain of the 427 kDa skeletal muscle dystrophin, we investigated the membrane cytoskeletal properties of dystrophin isoforms from rabbit skeletal muscle, heart and brain. All isoforms identified, including the abundant brain isoforms Dp116 which lacks the amino-terminal actin-binding domain of 427 kDa dystrophin, exhibited similar biochemical properties, i.e. insolubility in non-ionic detergent but extraction from the membrane with alkaline solutions. In muscle, beta-dystroglycan was found to be more tightly associated with dystrophin than alpha-sarcoglycan. These findings agree with the proposed structure of identified muscle and brain dystrophin isoforms and are also consistent with the current model of the dystrophin-glycoprotein complex.

12 children with handicapping problems were taught various strategies during a two-year period. These programs, designed to enrich their appreciation and awareness of the sounds of letters and how they are used, increased the children's attention span, parental participation with children and teacher, and promoted active involvement in reading.