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Frontiers in Neuroscience 2024Alcohol use disorder (AUD) is commonly associated with anxiety disorders and enhanced stress-sensitivity; symptoms that can worsen during withdrawal to perpetuate...
INTRODUCTION
Alcohol use disorder (AUD) is commonly associated with anxiety disorders and enhanced stress-sensitivity; symptoms that can worsen during withdrawal to perpetuate continued alcohol use. Alcohol increases neuroimmune activity in the brain. Our recent evidence indicates that alcohol directly modulates neuroimmune function in the central amygdala (CeA), a key brain region regulating anxiety and alcohol intake, to alter neurotransmitter signaling. We hypothesized that cannabinoids, such as cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), which are thought to reduce neuroinflammation and anxiety, may have potential utility to alleviate alcohol withdrawal-induced stress-sensitivity and anxiety-like behaviors via modulation of CeA neuroimmune function.
METHODS
We tested the effects of CBD and CBD:THC (3:1 ratio) on anxiety-like behaviors and neuroimmune function in the CeA of mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure (CIE). We further examined the impact of CBD and CBD:THC on alcohol withdrawal behaviors in the presence of an additional stressor.
RESULTS
We found that CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-h withdrawal. At 24-h withdrawal, CBD alone reduced anxiety-like behaviors while CBD:THC had mixed effects, showing increased center time indicating reduced anxiety-like behaviors, but increased immobility time that may indicate increased anxiety-like behaviors. These mixed effects may be due to altered metabolism of CBD and THC during alcohol withdrawal. Immunohistochemical analysis showed decreased S100β and Iba1 cell counts in the CeA at 4-h withdrawal, but not at 24-h withdrawal, with CBD and CBD:THC reversing alcohol withdrawal effects..
DISCUSSION
These results suggest that the use of cannabinoids during alcohol withdrawal may lead to exacerbated anxiety depending on timing of use, which may be related to neuroimmune cell function in the CeA.
PubMed: 38957186
DOI: 10.3389/fnins.2024.1375440 -
Trauma Case Reports Aug 2024An extensive abdominal wall defect is rare but severe trauma. Here, we have described the case of a male patient in his 20s who sustained extensive abdominal wall injury...
An extensive abdominal wall defect is rare but severe trauma. Here, we have described the case of a male patient in his 20s who sustained extensive abdominal wall injury and intra-abdominal organ damage after being caught in a noodle stirring machine. We used ABTHERA as a substitute for a defective abdominal wall, achieved open abdominal management and temporary closure of a wide abdominal wall defect, and performed staged reconstruction surgery.
PubMed: 38957173
DOI: 10.1016/j.tcr.2024.101058 -
Avicenna Journal of Medicine Apr 2024Schmidt's syndrome, or autoimmune polyendocrine syndrome type 2 (APS-2), is an uncommon disorder characterized by the co-occurrence of autoimmune thyroiditis and...
Schmidt's syndrome, or autoimmune polyendocrine syndrome type 2 (APS-2), is an uncommon disorder characterized by the co-occurrence of autoimmune thyroiditis and adrenalitis. APS-2 is defined as a combination of Addison's disease, autoimmune thyroid disease, and/or type 1 diabetes mellitus. It is an autosomal dominantly inherited polygenic disorder with incomplete penetrance; the candidate genes include but are not limited to HLA-DR3, HLA-DR4, CTLA-4, PTPN22, and CD25-IL-2. Autoimmune thyroiditis, often Hashimoto's disease, results in hypothyroidism. Primary adrenal failure results in enhanced secretion of adrenocorticotrophic hormone melanocyte and co-secretion of melanocyte-stimulating hormone, contributing to hyperpigmentation. Mineralocorticoid deficiency results in salt wasting, fatigue and cramps, postural hypotension, and hyperkalemia. Cortisol, an insulin counter-regulatory hormone, plays a pivotal role in maintaining euglycemia; deficiency predisposes to the development of hypoglycemia. We here report a rare presentation of Schmidt's syndrome as hypoinsulinemic hypoglycemia in a middle-aged male patient. Management includes treatment of acute hypoglycemic episodes with glucose or glucagon, long-term glucocorticoids and mineralocorticoids for adrenal insufficiency, and thyroid hormone supplements for hypothyroidism. This case report and brief overview aim to contribute to the scientific understanding of Schmidt's syndrome/APS-2. Additionally, here we briefly outline the diagnostic challenges in hypoglycemia evaluation, including the utilization of Whipple's triad and the gold standard supervised 72-hour fast and evaluation for primary adrenal and thyroid insufficiencies.
PubMed: 38957156
DOI: 10.1055/s-0044-1779745 -
Ophthalmic Genetics Jul 2024BCL6 co-repressor () gene variants are involved in oculofaciocardiodental (OFCD) syndrome, acute myeloid leukaemia, renal tumours, and photoreceptor degenerative...
BACKGROUND
BCL6 co-repressor () gene variants are involved in oculofaciocardiodental (OFCD) syndrome, acute myeloid leukaemia, renal tumours, and photoreceptor degenerative diseases. Here, we describe a British family with a pathogenic heterozygous variant in the gene causing congenital nuclear cataract.
METHODS
Whole-exome sequencing was conducted on an individual affected by X-linked dominant congenital cataract in a three-generation family to establish the underlying genetic basis. Bioinformatics analysis confirmed the variants with damaging pathogenicity scores.
RESULTS
A novel likely pathogenic frameshift variant NM_001123385.1: c.3621del; p.Lys1207AsnfsTer31, was identified and found to co-segregate with the disease in this family.
CONCLUSIONS
This is apparently the first report of a variant in causing X-linked dominant congenital cataract which is potentially isolated or presenting with a remarkably mild systemic phenotype. Our findings extend the genetic basis for congenital cataract and add to the phenotypic spectrum of variants.
PubMed: 38957147
DOI: 10.1080/13816810.2024.2373248 -
Scandinavian Journal of Pain Jan 2024
Topics: Humans; Galvanic Skin Response; Male; Female; Adult; Temperature; Young Adult
PubMed: 38957143
DOI: 10.1515/sjpain-2024-0033 -
Current Opinion in Pediatrics Jun 2024To review the updated 2023 Allergy Immunology Joint Task Force on Practice Parameters (JTFPP) GRADE and Institute of Medicine (IOM) Based Guidelines for the management...
PURPOSE OF REVIEW
To review the updated 2023 Allergy Immunology Joint Task Force on Practice Parameters (JTFPP) GRADE and Institute of Medicine (IOM) Based Guidelines for the management of atopic dermatitis.
RECENT FINDINGS
Topical corticosteroids and/or calcineurin inhibitors are recommended in individuals with atopic dermatitis refractory to moisturizer alone and may be used to maintain remission after acute flare control is achieved. Calcineurin inhibitors are a class of immunosuppressants used to effectively manage different autoimmune disorders. Bleach baths and allergen immunotherapy may be beneficial for individuals with moderate-to-severe disease, while elimination diets, azathioprine, methotrexate, mycophenolate, and systemic corticosteroids are not recommended. Dupilumab is strongly recommended for refractory atopic dermatitis. Oral Janus kinase (JAK) inhibitors carry significant risks; however, this class of medicines may be considered in cases of severe or refractory atopic dermatitis with intolerance to dupilumab. Patient preferences regarding cost, availability, feasibility, and tolerability should be integrated into all treatment plans using a shared decision-making approach.
SUMMARY
The 2023 JTFPP Atopic Dermatitis Guidelines offer up-to-date guidance for the management of atopic dermatitis of varying severity in infants, children, and adults.
PubMed: 38957084
DOI: 10.1097/MOP.0000000000001381 -
Scandinavian Cardiovascular Journal :... Jun 2024Electrocardiogram (ECG) and measurement of plasma brain natriuretic peptides (BNP) are established markers of right ventricular dysfunction (RVD) in the setting of acute...
OBJECTIVES
Electrocardiogram (ECG) and measurement of plasma brain natriuretic peptides (BNP) are established markers of right ventricular dysfunction (RVD) in the setting of acute pulmonary embolism (PE) but their value at long-term follow-up is largely unknown. The purpose of this prospective study was to determine the prevalence of ECG abnormalities, describe levels of N-terminal proBNP (NT-proBNP), and establish their association with dyspnea at long-term follow-up after PE.
DESIGN
All Swedish patients diagnosed with acute PE in 2005 ( = 5793) were identified through the Swedish National Patient Registry. Surviving patients in 2007 ( = 3510) were invited to participate. Of these, 2105 subjects responded to a questionnaire about dyspnea and comorbidities. Subjects with dyspnea or risk factors for development of chronic thromboembolic pulmonary hypertension were included in the study in a secondary step, which involved collection of blood samples and ECG registration.
RESULTS
Altogether 49.3% had a completely normal ECG. The remaining participants had a variety of abnormalities, 7.2% had atrial fibrillation/flutter (AF). ECG with any sign of RVD was found in 7.2% of subjects. Right bundle branch block was the most common RVD sign with a prevalence of 6.4%. An abnormal ECG was associated with dyspnea. AF was associated with dyspnea, whereas ECG signs of RVD were not. 61.2% of subjects had NT-proBNP levels above clinical cut-off (>125 ng/L). The degree of dyspnea did not associate independently with NT-proBNP levels.
CONCLUSIONS
We conclude that the value of ECG and NT-proBNP in long term follow-up after PE lies mostly in differential diagnostics.
Topics: Humans; Pulmonary Embolism; Peptide Fragments; Male; Female; Natriuretic Peptide, Brain; Electrocardiography; Sweden; Biomarkers; Aged; Prospective Studies; Dyspnea; Middle Aged; Registries; Time Factors; Predictive Value of Tests; Prevalence; Ventricular Dysfunction, Right; Risk Factors; Aged, 80 and over; Prognosis; Ventricular Function, Right; Bundle-Branch Block
PubMed: 38957080
DOI: 10.1080/14017431.2024.2373090 -
Australian Journal of General Practice Jul 2024Many Australians, particularly the elderly, suffer from eye diseases that require treatment with regular injections given into the eye. These injections can result in...
BACKGROUND
Many Australians, particularly the elderly, suffer from eye diseases that require treatment with regular injections given into the eye. These injections can result in complications, some of which can be vision threatening.
OBJECTIVE
To summarise some of the more common reasons for intraocular injection, as well as some common and/or more serious complications of intraocular injection that might present to general practitioners.
DISCUSSION
Intraocular injection is an increasingly common means of treatment for a range of eye conditions. Serious complications, although rare, often require acute intervention to achieve the best outcomes, and timely referral of patients with worrying symptoms is important to achieve optimum patient care.
Topics: Humans; Injections, Intraocular; Eye Diseases; Australia
PubMed: 38957063
DOI: 10.31128/AJGP-08-23-6944 -
Journal of Cellular and Molecular... Jul 2024Pruritus is often accompanied with bacterial infections, but the underlying mechanism is not fully understood. Although previous studies revealed that...
Pruritus is often accompanied with bacterial infections, but the underlying mechanism is not fully understood. Although previous studies revealed that lipopolysaccharides (LPS) could directly activate TRPV4 channel and TRPV4 is involved in the generation of both acute itch and chronic itch, whether and how LPS affects TRPV4-mediated itch sensation remains unclear. Here, we showed that LPS-mediated TRPV4 sensitization exacerbated GSK101-induced scratching behaviour in mice. Moreover, this effect was compromised in TLR4-knockout mice, suggesting LPS acted through a TLR4-dependent mechanism. Mechanistically, LPS enhanced GSK101-evoked calcium influx in mouse ear skin cells and HEK293T cells transfected with TRPV4. Further, LPS sensitized TRPV4 channel through the intracellular TLR4-PI3K-AKT signalling. In summary, our study found a modulatory role of LPS in TRPV4 function and highlighted the TLR4-TRPV4 interaction in itch signal amplification.
Topics: TRPV Cation Channels; Animals; Toll-Like Receptor 4; Pruritus; Lipopolysaccharides; Humans; Signal Transduction; Mice; HEK293 Cells; Phosphatidylinositol 3-Kinases; Mice, Knockout; Mice, Inbred C57BL; Male; Calcium; Proto-Oncogene Proteins c-akt
PubMed: 38957035
DOI: 10.1111/jcmm.18509 -
ARP Rheumatology 2024Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an emerging adult-onset systemic autoinflammatory disorder affecting multiple organ systems.... (Review)
Review
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an emerging adult-onset systemic autoinflammatory disorder affecting multiple organ systems. While lung involvement is common in this syndrome, literature regarding specific patterns is sparse. In this report, we present a case description of a patient with VEXAS syndrome who presented at the emergency department on two separate occasions with acute interstitial pneumonia (AIP) and diffuse alveolar hemorrhage (DAH). A literature review with a comparison of our observed findings to the general findings of VEXAS syndrome, AIP, and DAH is provided. This report underscores the rarity of specific pulmonary manifestations associated with VEXAS syndrome, contributing valuable insight to the limited literature available on this topic.
Topics: Humans; Lung Diseases, Interstitial; Hemorrhage; Pulmonary Alveoli; Male; Genetic Diseases, X-Linked; Lung Diseases; Vacuoles; Middle Aged; Syndrome; Ubiquitin-Activating Enzymes
PubMed: 38956997
DOI: No ID Found