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Tremor Following Guillain Barré Syndrome
No full textBackground: Neuropathic tremor occurs with damage to the peripheral nervous system. Guillain-Barré syndrome (GBS) causes acute paralysis following nerve inflammation sometimes resulting in long-term disability. It is unclear how frequent and severe tremor is following GBS. Objectives: We aimed to assess the frequency and features of tremor following GBS. Methods: We enrolled 18 patients with GBS treated in a secondary care center within a 4-year period. Evaluations were done with the Fahn-Tolosa-Marin tremor rating scale (FTM-TRS). We compared these features with a cohort of consecutive patients with untreated essential tremor (ET). Results: There were 13 males and 5 females with a mean age at evaluation (S.D.) of 41.5 ± 14.0 years and at GBS onset of 40.2 ± 13.7. No patient had history of tremor before GBS. Upper limb tremor was identified in 16 (89%) cases, 35.5% of patients had FTM-TRS score ≥10 points. Tremor was mostly kinetic, jerky with low amplitude with a total score of 10.94 ± 11.84 in the FTM-TRS. Compared with patients with ET, those with GBS-tremor were younger and had lower scores in all subscales of the FTM-TRS (P value \u3c 0.05 for all comparisons). In a multivariate linear regression analysis “days of hospitalization” had a positive association with the total FTM-TRS score (P = 0.001). Conclusions: Tremor was common following GBS. This tremor is mild compared with patients with ET, but adds functional impact
Good Publication Practice (GPP) Guidelines for Company-Sponsored Biomedical Research From the Point of View of the Diverse Authors Involved in Its Publication
No full textNationwide Analysis of the Outcomes and Mortality of Hospitalized Infants With Concomitant Diagnosis of COVID-19
No full textObjective: Coronavirus disease 2019 (COVID-19) generally causes milder illness in the pediatric population. However, infants represent a higher-risk population with evolving symptomatology and severity. There is a paucity of large population-based data on the impact of COVID-19 on hospitalized infants. Study Design: In this large cohort study, the National Inpatient Sample database was queried for all infant hospital admissions between January and December 2020 in the United States, with and without a diagnosis of COVID-19 based on ICD-10-CM U07. The mortality and morbidity of infants with and without COVID-19 were evaluated. Parent-reported race and outcomes were also analyzed. Results: A weighted total of 3,754,236 infants who were hospitalized were identified, of which 4,265 patients (0.11%) had a concomitant diagnosis of COVID-19. Infants with COVID-19 had similar mortality and extracorporeal membrane oxygenation utilization. Infants with concomitant COVID-19 had a higher rate of respiratory failure, congestive heart failure, acute kidney injury, and coagulopathy. Compared with Caucasian infants and Asian infants, Hispanic and African American infants were more likely to have COVID-19 hospital admissions than hospitalizations without COVID-19 diagnosis. Patients with lower median household income represented the majority of the COVID-19 hospitalization. The infants with COVID-19 were more likely to have Medicaid or Medicare insurance and less likely to have private insurance. Conclusion: In this large cohort of hospitalized infants with COVID-19, the infection was associated with complications, including respiratory failure and endotracheal intubations but not associated with a higher risk for mortality. Infants from racial minorities and lower socioeconomic strata carry the highest burden of COVID-19 infection
Remodeling Anaplastic Thyroid Cancer’s Aggressive Profile and Metabolic Signature by Natural Alkaloid Berberine
Get PDFAnaplastic thyroid cancer is a rare, fatal cancer with a five-year survival of 4%. Universally diagnosed at stage IV, anaplastic thyroid cancer is characterized by its lack of differentiation, rapid proliferative rate, highly inflammatory tumor microenvironment, and metabolic dysregulation. Refractory to all established therapies, anaplastic thyroid cancer requires a novel therapeutic approach that targets all of these drivers of anaplastic thyroid cancer carcinogenesis. We propose natural alkaloid berberine as a therapeutic with multitarget efficacy to alter mitochondrial metabolism and reprogram anaplastic thyroid cancer’s aggressive phenotype. Our in vitro model uses monocyte cell line U937, anaplastic thyroid cancer cell lines T238 and SW1736, and immortalized normal thyroid cell line Nthy-ori-3-1. Validation of in vitro findings via RNA Sequencing was conducted by Genewiz from Azenta and Qiagen’s Ingenuity Pathway Analysis was used for in silico modeling.
In targeting the aggressiveness of anaplastic thyroid disease, berberine selectively slowed proliferation by 80% in anaplastic thyroid cancer cells from 48 to 72 hours while sparing normal cells. Berberine reduced migratory capacity by 33% in T238 cells and 51% in SW1736 cells after 24 hours. Berberine reduced both migration and invasion by 30% in T238. These observations were substantiated by Western blot analysis – berberine selectively decreased phosphorylation of MEK, ERK, and ribosomal protein S6, crucial downstream regulators of the pro-proliferative and pro-survival pathways in anaplastic thyroid cancer cells. Further, berberine specifically modulated cancer-associated metabolism as observed through an increase in AMPKα phosphorylation, a major rate-limiting protein in cancer-induced dysregulation with an anti-tumor effect.
Modeling the anaplastic thyroid cancer tumor microenvironment, U937 cells were activated and polarized into a proinflammatory macrophage phenotype. Following berberine treatment at the activation/polarization stages, 19 soluble inflammatory mediators were significantly downregulated in the conditioned media compared to controls. U937 cells polarized using anaplastic thyroid cancer-conditioned media pre-treated with berberine also showed decreased IFN-γ and TNF-α secretion.
Validation of in vitro findings via RNA Sequencing revealed more than 400 significantly differentially expressed genes involved in mitochondrial metabolism, glycometabolism, sirtuin signaling, apoptosis, and proliferation. Following a comprehensive analysis, we identified significant downregulation of 22 of 37 total mitochondrially encoded genes and 13 of 13 mitochondrially encoded protein-coding genes comprising the oxidative phosphorylation complexes, illuminating a clear link between berberine treatment and altered mitochondrial metabolism in anaplastic thyroid cancer. Additionally, protein expression of significantly downregulated mitochondrial genes identified via RNA Sequencing was validated via Western blot, demonstrating decreased mitochondrially-encoded protein expression related to oxidative phosphorylation.
This work reveals a novel role for berberine as an inhibitor of mitochondrial metabolism that can be used to reprogram the aggressive nature of anaplastic thyroid cancer and open the door for promising combination therapy in treating fatal anaplastic thyroid cancer
Subclinical Persistence of Residual Acral Melanoma in Situ After Treatment With Topical Imiquimod and Retinoid Creams
No full textA Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder
No full textAlcohol use disorder (AUD) is a significant contributor to morbidity and mortality in the United States. It contributes to over 140,000 annual deaths, to over 200 related diseases and health conditions globally, and accounts for 5.1% of the global disease burden. Despite its substantial impact, AUD remains undertreated, marked by a scarcity of approved medications. This paper explores the current treatment landscape and novel strategies for both alcohol withdrawal syndrome and AUD. Promising results, including the use of psychedelics alongside psychotherapy, noninvasive neural-circuit-based interventions, phosphodiesterase-4 inhibitors, and GLP-1 receptor agonists, have emerged from recent studies. While these advancements show potential, further research is crucial for a comprehensive understanding of their effectiveness. The clear shortage of approved medications and other treatment modalities underscores the pressing need for ongoing research
Acceptability of Antipsychotic Transdermal Patch for Acute Schizophrenia: A Systematic Review and Meta-Analysis
No full textThe Interplay of Gut Microbiota and Their Metabolites as Potential Regulators of Resilience or Susceptibility to Traumatic Stress in Male and Female Rats
Get PDFExposure to traumatic stress is a major risk factor for the development of mood disorders in a subpopulation of individuals, while others remain resilient. Notably, women are twice as likely as men to develop affective disorders in the aftermath of trauma. The mechanisms and contributing factors that influence sex-related disparities in mood disorders and variations in resilience remain unclear. We hypothesized that sex-specific inter-individual differences in microbial composition, functionality, and metabolites would contribute to host resilience or susceptibility to stress-induced psychopathologies. In this study, we used single prolonged stress (SPS), an animal model of Post- Traumatic Stress Disorder (PTSD), to characterize pre-existing and trauma-induced differences in microbial, immunological, and molecular factors of stress-susceptible and stress-resilient male and female rats. Additionally, we investigated whether the microbial metabolite acetate could ameliorate SPS-triggered behavioral and molecular impairments. In aims 1 and 2 two cohorts of male and female Sprague-Dawley rats were randomly assigned to unstressed controls or groups exposed to SPS. Two weeks after SPS, all rats underwent a battery of behavioral tests. Based on their anxiety measures, the animals in the SPS group were further subdivided into resilient (SPS-R) and susceptible (SPS-S) subgroups. After the last behavioral test, the rats were euthanized, and different organs were collected. Additionally, stool samples were collected from each rat before and after SPS, and urine samples were collected before and 30 min into the immobilization step of SPS. Comparative analysis of fecal 16S sequencing before and after SPS exposure indicated significant sex-specific and group differences in gut microbial composition, functionality, and metabolites of the SPS-R and SPS-S subgroups. Additionally, alterations in the sympathoadrenal axis, blood-brain barrier permeability, and neuroinflammation were evident, especially in the SPS-S subgroups of each sex compared to their respective SPS-R subgroups. Across the study, alpha diversity remained consistently lower in males compared to females. Beta diversity revealed distinct separations between male and female susceptible groups before SPS, with this separation becoming evident in resilient groups following SPS. At the genus level, Lactobacillus, Lachnospiracaeae_Incertae_Sedis, and Barnesiella exhibited sex-specific alterations, displaying opposing abundances in the SPS-R and SPS-S subgroups for each sex. In line with the alterations observed in the gut microbiota, the levels of cecal short-chain fatty acids (SCFA) were also different, with SPS-S females having significantly higher levels of branchedchain SCFAs, whereas SPS-S males had lower levels of acetate compared to their respective SPSR subgroups. Lower levels of cecal acetate were also inversely and significantly correlated with anxiety index. To further examine the anxiolytic properties of acetate, in aim 3 a separate cohort of male rats was divided into unstressed controls or SPS-exposed groups and received continued oral supplementation of either 150 mM sodium acetate or 150 mM sodium chloride-matched water. Oral supplementation with acetate ameliorated SPS-induced physiological and behavioral impairments, induced epigenetic modifications, inhibited neuroinflammation, and increased serum β-hydroxybutyrate levels without affecting unstressed controls. Collectively, our results indicate, for the first time, preexisting and trauma-induced differences in the gut microbial composition, functionality, and metabolites of male and female rats that relate to their ability to cope with traumatic stress. Further characterization of these factors will be crucial for understanding susceptibility and fostering resilience, especially in females, who are more likely than males to develop mood disorders. Additionally, by demonstrating a causal relationship between oral acetate treatment and the mitigation of several SPS-induced behavioral impairments, our study highlights the preventive therapeutic potential of acetate supplementation in alleviating adverse responses to traumatic stress
