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Communications Biology Nov 2023Infectious prions consist of PrP, a misfolded, aggregation-prone isoform of the host's prion protein. PrP assemblies encode distinct biochemical and biological...
Infectious prions consist of PrP, a misfolded, aggregation-prone isoform of the host's prion protein. PrP assemblies encode distinct biochemical and biological properties. They harbor a specific profile of PrP species, from small oligomers to fibrils in different ratios, where the highest infectivity aligns with oligomeric particles. To investigate the impact of PrP aggregate complexity on prion propagation, biochemical properties, and disease pathogenesis, we fractionated elk prions by sedimentation velocity centrifugation, followed by sub-passages of individual fractions in cervidized mice. Upon first passage, different fractions generated PrP with distinct biochemical, biophysical, and neuropathological profiles. Notably, low or high molecular weight PrP aggregates caused different clinical signs of hyperexcitability or lethargy, respectively, which were retained over passage, whereas other properties converged. Our findings suggest that PrP quaternary structure determines an initial selection of a specific replication environment, resulting in transmissible features that are independent of PrP biochemical and biophysical properties.
Topics: Mice; Animals; Prion Diseases; Prions; Prion Proteins
PubMed: 37964018
DOI: 10.1038/s42003-023-05541-3 -
Ear, Nose, & Throat Journal Sep 2023Deep neck infections are common in infants and occur in several anatomic subsites including the retropharyngeal space. Retropharyngeal abscesses are significant given... (Review)
Review
Deep neck infections are common in infants and occur in several anatomic subsites including the retropharyngeal space. Retropharyngeal abscesses are significant given their propensity for mediastinal extension and can have life-threatening sequelae. We present 3 cases of retropharyngeal abscess with mediastinal extension in infants. In one case, an incompletely vaccinated 10-month-old boy presented with cough, rhinorrhea, and fever. Despite antibiotic treatment, he developed Horner's syndrome and hypoxia. A computed tomography (CT) scan showed a C1-T7 retropharyngeal abscess. He underwent transoral incision and drainage and recovered fully. In another case, a 12-month old infant presented with 8 days of fever and neck pain. A CT scan showed a retropharyngeal collection extending to the mediastinum and right hemithorax. Transoral incision and drainage and video-assisted thoracoscopic surgery thoracotomy were performed for abscess drainage. He recovered fully with antibiotics. In the third case, an 8-month-old boy presented to the emergency room following several days of fever, lethargy, and decreased neck range of motion. A CT scan showed a large retropharyngeal abscess that required both transoral and transcervical drainage. His case was complicated by septic shock, yet the patient eventually made a full recovery.
Topics: Male; Infant; Humans; Retropharyngeal Abscess; Mediastinum; Neck; Anti-Bacterial Agents; Drainage
PubMed: 37309202
DOI: 10.1177/01455613231178975 -
Brain and Nerve = Shinkei Kenkyu No... Dec 2023The Labours of Hercules, written by Agatha Christie, contains twelve short stories, with 'atropine' playing a crucial role in the seventh story, The Cretan Bull (1939)....
The Labours of Hercules, written by Agatha Christie, contains twelve short stories, with 'atropine' playing a crucial role in the seventh story, The Cretan Bull (1939). Atropine easily crosses the blood-brain barrier (BBB), leading to central nervous system (CNS) side effects such as delirium, hallucinations, disorientation, memory problems, coma or stupor, and convulsive seizures when overdosed. In this episode, a concentrated form of atropine obtained from prescribed eye drops was misused to induce a hereditary incurable neurodegenerative disorder, similar to Huntington's Chorea, in the client's fiancée. However, Mr. Poirot discerned this by careful examination of his symptoms and resolved the case.
Topics: Male; Animals; Cattle; Humans; Atropine; Atropa belladonna; Seizures; Hallucinations; Blood-Brain Barrier
PubMed: 38097222
DOI: 10.11477/mf.1416202532 -
Schizophrenia Research Jan 2024Catatonia is widely under-detected, and the many differences across catatonia rating scales and diagnostic criteria could be a key reason why clinicians have a hard time... (Review)
Review
BACKGROUND
Catatonia is widely under-detected, and the many differences across catatonia rating scales and diagnostic criteria could be a key reason why clinicians have a hard time knowing what catatonia looks like and what constitutes each of its features.
METHODS
This review begins by discussing the nature of catatonia diagnosis, its evolution in ICD and DSM, and different approaches to scoring. The central analysis then provides a descriptive survey of catatonia's individual signs across scales and diagnostic criteria. The goal of this survey is to characterize distinctions across scales and diagnostic criteria that can introduce variance into catatonia caseness.
RESULTS
Diagnostic criteria for catatonia in DSM-5-TR and ICD-11 are broadly aligned in terms of which items are included, item definitions and number of items required for diagnosis; however, the lack of item thresholds is a fundamental limitation. Many distinctions across scales and criteria could contribute to diagnostic discordance.
DISCUSSION
Clear, consistent definitions for catatonia features are essential for reliable detection. Of available scales, Bush-Francis and Northoff can be converted to diagnostic criteria with limited modification. Bush-Francis is the most efficient, with a screening instrument, videographic resources and standardized clinical assessment. Northoff offers the most detailed assessment and uniquely emphasizes emotional and volitional disturbances in catatonia.
CONCLUSIONS
The field's understanding of the catatonia phenotype has advanced considerably over the past few decades. However, this review reveals many important limitations in the ICD and DSM as well as differences across scales and criteria that stand in the way of reliable catatonia detection.
Topics: Humans; Catatonia; Psychiatric Status Rating Scales; Diagnostic and Statistical Manual of Mental Disorders; International Classification of Diseases; Surveys and Questionnaires
PubMed: 35995651
DOI: 10.1016/j.schres.2022.08.002 -
Schizophrenia Research Jan 2024Catatonia is a complex psychomotor disorder characterized by motor, affective, and behavioral symptoms. Despite being known for almost 150 years, its pathomechanisms...
BACKGROUND
Catatonia is a complex psychomotor disorder characterized by motor, affective, and behavioral symptoms. Despite being known for almost 150 years, its pathomechanisms are still largely unknown.
METHODS
A systematic research on PubMed, Web of Science, and Scopus was conducted to identify neuroimaging studies conducted on group or single individuals with catatonia. Overall, 33 studies employing structural magnetic resonance imaging (sMRI, n = 11), functional magnetic resonance imaging (fMRI, n = 10), sMRI and fMRI (n = 2), functional near-infrared spectroscopy (fNIRS, n = 1), single positron emission computer tomography (SPECT, n = 4), positron emission tomography (PET, n = 4), and magnetic resonance spectroscopy (MRS, n = 1), and 171 case reports were retrieved.
RESULTS
Observational sMRI studies showed numerous brain changes in catatonia, including diffuse atrophy and signal hyperintensities, while case-control studies reported alterations in fronto-parietal and limbic regions, the thalamus, and the striatum. Task-based and resting-state fMRI studies found abnormalities located primarily in the orbitofrontal, medial prefrontal, motor cortices, cerebellum, and brainstem. Lastly, metabolic and perfusion changes were observed in the basal ganglia, prefrontal, and motor areas. Most of the case-report studies described widespread white matter lesions and frontal, temporal, or basal ganglia hypoperfusion.
CONCLUSIONS
Catatonia is characterized by structural, functional, perfusion, and metabolic cortico-subcortical abnormalities. However, the majority of studies and case reports included in this systematic review are affected by considerable heterogeneity, both in terms of populations and neuroimaging techniques, which calls for a cautious interpretation. Further elucidation, through future neuroimaging research, could have great potential to improve the description of the neural motor and psychomotor mechanisms underlying catatonia.
Topics: Humans; Brain; Catatonia; Cerebellum; Magnetic Resonance Imaging; Motor Cortex
PubMed: 36404217
DOI: 10.1016/j.schres.2022.11.002 -
Clinical Case Reports Sep 2023A 31-year-old female with a diagnosis of bipolar disorder developed black hairy tongue after alprazolam therapy. Her symptom resolved 10 days after the cessation of...
KEY CLINICAL MESSAGE
A 31-year-old female with a diagnosis of bipolar disorder developed black hairy tongue after alprazolam therapy. Her symptom resolved 10 days after the cessation of alprazolam.
ABSTRACT
Alprazolam is a widely used antidepressant and antianxiety drug. Mild to moderate side effect of alprazolam was commonly seen, including lethargy, dizziness, headache, dry mouth, nausea, fatigue, constipation, and blurred vision. In this case, we reported a patient developed black hairy tongue after alprazolam intake, and her symptom resolved after 10-day discontinuation of alprazolam. This rare adverse event should be of concern to clinicians. This is the first paper to report an alprazolam-induced BHT. This rare side effect of alprazolam should be concern of clinicians; we hope our report will promote the understand of BHT and acknowledge clinicians of this rare side effect of alprazolam.
PubMed: 37636887
DOI: 10.1002/ccr3.7831 -
Cureus Sep 2023Levothyroxine (LT) is the synthetic form of thyroxine (T4), a thyroid hormone analog used to treat hypothyroidism. LT overdose rarely results in severely poor outcomes....
Levothyroxine (LT) is the synthetic form of thyroxine (T4), a thyroid hormone analog used to treat hypothyroidism. LT overdose rarely results in severely poor outcomes. General guidelines for treating exogenous thyrotoxicosis depend on the severity of symptoms. There is no standardized protocol; however, drug discontinuation, beta-blockers (specifically propranolol), and cholestyramine effectively manage overdose when needed, with most cases resolving independently without medical intervention. Here, we present the case of a 26-year-old female with a history of supraventricular tachycardia, anxiety, depression, and Hashimoto thyroiditis who was accidentally overprescribed LT (300 mcg for one and a half months) that resulted in symptoms of lethargy, tremors, body temperature dysregulation, orthostatic hypotension, and diarrhea. This case, with limited evidence, suggests that excessive LT exacerbated the patient's underlying psychiatric symptoms, encouraging suicidal ideation.
PubMed: 37809152
DOI: 10.7759/cureus.44787 -
Diagnostics (Basel, Switzerland) Nov 2023The term "Osmotic Demyelination Syndrome" (ODS) is synonymous with central pontine myelinolysis (CPM), denoting a condition characterised by brain damage, particularly...
The term "Osmotic Demyelination Syndrome" (ODS) is synonymous with central pontine myelinolysis (CPM), denoting a condition characterised by brain damage, particularly affecting the white matter tracts of the pontine region. This damage arises due to the rapid correction of metabolic imbalances, primarily cases of hyponatremia. Noteworthy triggers encompass severe burns, liver transplantations, anorexia nervosa, hyperemesis gravidarum, and hyperglycaemia, all linked to the development of CPM. Clinical manifestations encompass a spectrum of signs and symptoms, including dysphagia, dysarthria, spastic quadriparesis, pseudobulbar paralysis, ataxia, lethargy, tremors, disorientation, catatonia, and, in severe instances, locked-in syndrome and coma. A recent case involving a 45-year-old woman illustrates these complexities. Upon admission to the Medicine Intensive Care Unit, she presented with symptoms indicative of diminished responsiveness and bilateral weakness in the upper and lower limbs. Of significance, the patient had a pre-existing medical history of hyperthyroidism. Extensive diagnostic investigations were undertaken, revealing compelling evidence of profound hyponatremia through blood analyses. Furthermore, magnetic resonance imaging (MRI) was performed, unveiling conspicuous areas of abnormal hyperintensity located in the central pons, intriguingly accompanied by spared peripheral regions. These radiological findings align with the characteristic pattern associated with osmotic demyelination syndrome, illuminating the underlying pathology.
PubMed: 37958289
DOI: 10.3390/diagnostics13213393 -
Veterinary Clinical Pathology Dec 2023B-cell leukemia is a rare form of hematologic neoplasia in sheep, especially in adult animals. We present a case report of a 5-year-old WhiteFace Sheep wether with...
B-cell leukemia is a rare form of hematologic neoplasia in sheep, especially in adult animals. We present a case report of a 5-year-old WhiteFace Sheep wether with suspected acute lymphoblastic leukemia. The patient, a second-generation relative of ewes experimentally inoculated with atypical scrapie, exhibited acute lethargy and loss of appetite. Laboratory investigation revealed marked leukocytosis, lymphocytosis, and abnormal serum chemistry panel results. Microscopic examination of blood and bone marrow smears exhibited a high percentage of large neoplastic cells with lymphoid characteristics. Histopathologic analysis of the spleen, liver, lungs, and other organs confirmed the presence of widespread tissue infiltration by neoplastic cells. Immunohistochemical labeling demonstrated strong intracytoplasmic labeling for CD20, consistent with B-cell neoplasia. Flow cytometric analysis confirmed the B-cell lineage of the neoplastic cells. Screening for bovine leukemia virus, which can experimentally cause leukemia in sheep, yielded a negative result. In this case, the diagnosis of B-cell leukemia was supported by a comprehensive panel of diagnostic evaluations, including cytology, histopathology, immunohistochemistry, and immunophenotyping. This case report highlights the significance of accurate diagnosis and classification of hematologic neoplasia in sheep, emphasizing the need for immunophenotyping to aid in the diagnosis of B-cell leukemia. It also emphasizes the importance of considering spontaneous leukemia as a differential diagnosis in sheep with lymphoid neoplasia, especially in the absence of circulating infectious diseases.
Topics: Male; Animals; Sheep; Female; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Spleen; Lymphocytosis; Immunophenotyping; Flow Cytometry; Sheep Diseases
PubMed: 38012962
DOI: 10.1111/vcp.13303 -
Journal of Affective Disorders Mar 2024Women show higher prevalence of depression and different symptomatology than men, possibly influenced by sex hormones. Many transgender persons, who face a high risk of...
BACKGROUND
Women show higher prevalence of depression and different symptomatology than men, possibly influenced by sex hormones. Many transgender persons, who face a high risk of depression, use Gender-Affirming Hormone Therapy (GAHT), but the impact of GAHT on depressive symptom profiles is unknown.
METHODS
This study examined depressive symptoms in transgender persons before GAHT and after 3- and 12 months of GAHT. We used the Inventory of Depressive Symptomatology-Self Report to assess depressive symptoms, exploratory factor analysis (EFA) to assess symptom clusters, and linear mixed models to assess changes in symptom clusters.
RESULTS
This study included 110 transmasculine (TM) and 89 transfeminine (TF) participants. EFA revealed four symptom clusters: mood, anxiety, lethargy, and somatic symptoms. Changes in total depressive symptoms significantly differed between TM and TF groups. After 3 months of GAHT, TM participants reported improvement in lethargy (-16 %; 95%CI: -29 %; -2 %), and after 12 months TF participants reported worsening in low mood (24 %; 95%CI: 3 %; 51 %), but absolute score changes were modest. Neither group showed changes in anxiety or somatic symptoms.
LIMITATIONS
This study had limited sample sizes at 12 months follow-up and did not include relevant biological or psychosocial covariates.
DISCUSSION
Changes in depressive symptoms after GAHT use differ in TM and TF persons: TM persons report slight improvements in lethargy, whereas TF persons report a slight increase in low mood. Starting GAHT represents a significant life event with profound social and physical effects, and further research should assess social and biological effects of GAHT on mood-related symptoms.
Topics: Male; Female; Humans; Transgender Persons; Depression; Lethargy; Medically Unexplained Symptoms; Syndrome; Hormones
PubMed: 38154588
DOI: 10.1016/j.jad.2023.12.056