RATIONALE: Mescaline is a classical psychedelic compound with a phenylethylamine structure that primarily acts on serotonin 5-HT2A/C receptors, but also binds to 5-HT1A and 5-HT2B receptors. Despite being the first psychedelic ever isolated and synthesized, the precise role of different serotonin receptor subtypes in its behavioral pharmacology is not fully understood. OBJECTIVES: In this study, we aimed to investigate how selective antagonists of 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT1A receptors affect the behavioral changes induced by subcutaneous administration of mescaline (at doses of 10, 20, and 100 mg/kg) in rats. METHODS: We used adult male Wistar rats in all our experiments. We evaluated locomotor activity using the open field test, and assessed sensorimotor gating deficits by measuring prepulse inhibition (PPI) of acoustic startle reaction (ASR). RESULTS: While the highest dose of mescaline induced hyperlocomotion (p < 0.001), which almost all the other antagonists reversed (p < 0.05-0.001), the PPI deficits were selectively normalized by the 5-HT2A antagonist (p < 0.05-0.01). The 5-HT2C antagonist partially reversed the small PPI deficit induced by lower doses of mescaline (p = 0.0017). CONCLUSION: Our findings suggest that mescaline-induced changes in behavior are primarily mediated by the 5-HT2A receptor subtype, with less pronounced contributions from the 5-HT2C receptor. The other antagonists had limited effects.
- MeSH
- Serotonin 5-HT2 Receptor Antagonists pharmacology MeSH
- Serotonin Antagonists pharmacology MeSH
- Behavior, Animal * drug effects MeSH
- Hallucinogens pharmacology administration & dosage MeSH
- Rats MeSH
- Locomotion drug effects MeSH
- Mescaline * pharmacology MeSH
- Motor Activity drug effects MeSH
- Rats, Wistar * MeSH
- Prepulse Inhibition drug effects MeSH
- Receptor, Serotonin, 5-HT2A * metabolism drug effects MeSH
- Receptor, Serotonin, 5-HT2C * metabolism drug effects MeSH
- Reflex, Startle drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The 37th International Conference on Antiviral Research (ICAR) was held in Gold Coast, Australia, May 20-24, 2024. ICAR 2024 featured over 75 presentations along with two poster sessions and special events, including those specifically tailored for trainees and early-career scientists. The meeting served as a platform for the exchange of cutting-edge research, with presentations and discussions covering novel antiviral compounds, vaccine development, clinical trials, and therapeutic advancements. A comprehensive array of topics in antiviral science was covered, from the latest breakthroughs in antiviral drug development to innovative strategies for combating emerging viral threats. The keynote presentations provided fascinating insight into two diverse areas fundamental to medical countermeasure development and use, including virus emergence at the human-animal interface and practical considerations for bringing antivirals to the clinic. Additional sessions addressed a variety of timely post-pandemic topics, such as the hunt for broad spectrum antivirals, combination therapy, pandemic preparedness, application of in silico tools and AI in drug discovery, the virosphere, and more. Here, we summarize all the presentations and special sessions of ICAR 2024 and introduce the 38th ICAR, which will be held in Las Vegas, USA, March 17-21, 2025.
- MeSH
- Antiviral Agents * therapeutic use pharmacology MeSH
- COVID-19 MeSH
- COVID-19 Drug Treatment MeSH
- Humans MeSH
- Drug Discovery MeSH
- Drug Development MeSH
- Vaccine Development MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Congress MeSH
- Geographicals
- Australia MeSH
BACKGROUND: This study aimed to determine the differences in the cervical load and prevalence of Lactobacillus crispatus DNA, Lactobacillus iners DNA, Gardnerella vaginalis DNA, Sneathia sanguinegens DNA, and Ureaplasma species DNA between pregnant women with preterm prelabor rupture of membranes (PPROM) with and without a history of cervical excisional treatment. We also assessed the changes in the cervical load and prevalence of L. crispatus DNA, L. iners DNA, G. vaginalis DNA, S. sanguinegens DNA, and U. spp DNA. according to the cone length. METHODS: This retrospective study included 132 women with singleton pregnancies complicated by PPROM. For all women, information about the cervical loads of bacterial DNA corresponding to L. crispatus, L. iners, G. vaginalis, S. sanguinegens, and U. spp., which was assessed using PCR, was available. RESULTS: Women with a history of cervical excisional treatment had a higher cervical load of L. iners DNA (4.4 × 106 copies DNA/mL vs. 3.5 × 105 copies DNA/mL, p = .04) and a higher load and prevalence of U. spp. DNA (1.1 × 105 copies DNA/mL vs. 9.6 × 104 copies DNA/mL, p = .03; 2.7% vs. 0.5%, p = .04) than those without a history of cervical excisional treatment. In the subset of women with a history of cervical excisional treatment, those with a cone length 18 mm and more had a lower relative abundance of L. crispatus DNA (6% vs. 89%, p = .02), a higher load and relative abundance of L. iners DNA (1.1 × 107 copies DNA/mL vs. 8.2 × 105 copies DNA/mL, p = .04; 91% vs. 35%, p = .04), and higher loads of G. vaginalis DNA (7.6 × 104 copies DNA/mL vs. 3.2 × 102 copies DNA/mL, p = .02) than those with cone length < 18 mm. CONCLUSIONS: A history of cervical excisional treatment was associated with alterations in the cervical microbiota composition in pregnant women with PPROM.
- MeSH
- Cervix Uteri * microbiology surgery MeSH
- DNA, Bacterial analysis isolation & purification MeSH
- Adult MeSH
- Gardnerella vaginalis isolation & purification genetics MeSH
- Lactobacillus isolation & purification genetics MeSH
- Humans MeSH
- Microbiota MeSH
- Fetal Membranes, Premature Rupture * microbiology epidemiology MeSH
- Retrospective Studies MeSH
- Pregnancy MeSH
- Ureaplasma isolation & purification MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Very low carbohydrate high fat (VLCHF) diet and high-intensity interval training (HIIT) are widely utilized for weight reduction and cardiorespiratory fitness improvement, respectively. To assess the acceptability of these approaches, it is essential to examine mental health-related indicators. This secondary analysis of a randomized controlled trial investigated the isolated and synergistic effects of VLCHF and HIIT on mental health-related indicators in individuals with excessive weight or obesity. Sixty-eight participants (age = 42 ± 10.2; 20-60 years; BMI = 29.8 ± 3.7) were analysed across four groups: HIIT (n = 15, 4 males, 11 females), VLCHF (n = 19, 4 males, 15 females), VLCHF + HIIT (n = 19, 4 males, 15 females), and control (n = 15, 4 males, 11 females). The 12-week intervention, involved VLCHF diet or HIIT sessions, depending on group affiliation and completing online questionnaires via Qualtrics software before and after the intervention. The questionnaires included the 12-item Short Form Survey (SF-12) for mental (MHS) and physical health scores (PHS), the Satisfaction with Life Scale (SWLS), and the Perceived Stress Scale (PSS). Using the Kruskal-Wallis test, we found no significant differences in mental health-related indicators between groups after 12 weeks, except for SWLS (p = 0.031; ES = 0.133; medium), which improved significantly in the VLCHF + HIIT group compared to the HIIT group. Our findings indicate that HIIT and VLCHF, alone or combined, do not significantly affect mental health-related indicators.
- MeSH
- Diet, Carbohydrate-Restricted * methods MeSH
- Diet, High-Fat * adverse effects MeSH
- Adult MeSH
- Mental Health * MeSH
- Weight Loss MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Obesity * MeSH
- Randomized Controlled Trials as Topic MeSH
- High-Intensity Interval Training * methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Extramedullary disease (EMD) is a high-risk feature of multiple myeloma (MM) and remains a poor prognostic factor, even in the era of novel immunotherapies. Here, we applied spatial transcriptomics (RNA tomography for spatially resolved transcriptomics [tomo-seq] [n = 2] and 10x Visium [n = 12]) and single-cell RNA sequencing (n = 3) to a set of 14 EMD biopsies to dissect the 3-dimensional architecture of tumor cells and their microenvironment. Overall, infiltrating immune and stromal cells showed both intrapatient and interpatient variations, with no uniform distribution over the lesion. We observed substantial heterogeneity at the copy number level within plasma cells, including the emergence of new subclones in circumscribed areas of the tumor, which is consistent with genomic instability. We further identified the spatial expression differences between GPRC5D and TNFRSF17, 2 important antigens for bispecific antibody therapy. EMD masses were infiltrated by various immune cells, including T cells. Notably, exhausted TIM3+/PD-1+ T cells diffusely colocalized with MM cells, whereas functional and activated CD8+ T cells showed a focal infiltration pattern along with M1 macrophages in tumor-free regions. This segregation of fit and exhausted T cells was resolved in the case of response to T-cell-engaging bispecific antibodies. MM and microenvironment cells were embedded in a complex network that influenced immune activation and angiogenesis, and oxidative phosphorylation represented the major metabolic program within EMD lesions. In summary, spatial transcriptomics has revealed a multicellular ecosystem in EMD with checkpoint inhibition and dual targeting as potential new therapeutic avenues.
BACKGROUND: Telerehabilitation is a practical option for individuals with multiple sclerosis (MS) to engage in sustained physical activity without -visiting a rehabilitation facility. The aim of this systematic review was to evaluate the feasibility, effectiveness, safety, and adherence of exercise-based telerehabilitation as compared with usual care for MS patients. METHODS: A comprehensive literature search adhering to PRISMA guidelines was conducted, focusing on studies published in English since 2000. The systematic review protocol was registered in PROSPERO. The selection process involved strict criteria, including studies focusing on people with MS, telerehabilitation centred on regular exercise, a control group receiving usual care, valid exercise testing, and adherence to randomized controlled trial principles. Methodological quality was assessed using the TESTEX tool, ensuring rigour in study design and reporting. RESULTS: Among the 281 records screened, 10 studies met the criteria. Telerehabilitation interventions varied in format and outcomes were assessed using diverse exercise tests and questionnaires. Despite variations, the studies collectively demonstrated promising feasibility and safety, with minimal withdrawals and minor adverse events. Effectiveness varied, with 5 out of 10 studies showing significant improvements in the intervention group. Adherence rates ranged from 38% to 100%. CONCLUSION: In most of the assessed aspects, telerehabilitation is comparable to regular centre-based rehabilitation.
- MeSH
- Patient Compliance MeSH
- Exercise * MeSH
- Humans MeSH
- Multiple Sclerosis * rehabilitation MeSH
- Telerehabilitation * MeSH
- Exercise Therapy * methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Systematic Review MeSH
Sleep symptoms, including excessive sleepiness, are frequently reported by patients with functional motor disorders (FMD). We aimed to classify the comorbid sleep disorders in FMD, and to investigate the relationship between subjective sleepiness and objective measures of hypersomnia, comparing them with data from people with central hypersomnia. A total of 37 patients (mean [SD] age 46.4 [11.2] years) with clinically definite FMD, and 17 patients (mean [SD] age 41.1 [11.6] years) with central hypersomnia underwent structured medical and sleep history, neurological examination, polysomnography, multiple sleep latency test (MSLT), and questionnaires assessing sleepiness, fatigue, and depression. In all, 23 patients with FMD (62%) reported excessive daytime sleepiness. Evidence of specific sleep disorders was identified in our cohort, with 35% having restless legs syndrome; 49% obstructive sleep apnea; and 8% periodic limb movements in sleep; however, the presence of these disorders was not correlated with subjective sleepiness. Patients with FMD with self-reported sleepiness reported higher fatigue (p = 0.002), depression (p = 0.002), and had longer sleep latencies in the MSLT (p < 0.001) compared to the patients with central hypersomnia. No correlation was found between subjective and objective sleepiness in either group. Fatigue positively correlated with self-reported sleepiness in patients with FMD (p < 0.001). This study did not find objective correlates of increased sleepiness in patients with FMD. While sleep abnormalities were found to be common in FMD, they were not correlated with self-reports of excessive sleepiness. Positive correlations between self-reported sleepiness and fatigue support the current unified model of non-motor symptoms in FMD.
- MeSH
- Depression epidemiology physiopathology MeSH
- Adult MeSH
- Comorbidity * MeSH
- Middle Aged MeSH
- Humans MeSH
- Nocturnal Myoclonus Syndrome epidemiology physiopathology MeSH
- Polysomnography * MeSH
- Disorders of Excessive Somnolence * epidemiology physiopathology MeSH
- Sleep Wake Disorders epidemiology physiopathology MeSH
- Surveys and Questionnaires MeSH
- Sleepiness MeSH
- Sleep Latency physiology MeSH
- Restless Legs Syndrome physiopathology epidemiology MeSH
- Fatigue physiopathology epidemiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
AIMS: The present study aimed to assess vitamin D status and serum concentrations of pro-inflammatory cytokines IL-17, Il-23, and IL-18 in patients with chronic plaque psoriasis and their association with various demographic and clinical characteristics. METHODS: The study was conducted during the autumn/winter period on 48 patients with chronic plaque psoriasis and 48 controls. Total serum 25(OH)D level was determined with Roche Elecsys® 2010 Vitamin D total assay. Commercial ELISA kits were used for quantifying the serum levels of IL-17A, IL-18, and IL-23. RESULTS: Serum 25(OH)D had a median value of 16.95 ng/mL (IQR 10.8-23.50) for patients with psoriasis and 18.80 ng/mL (IQR 15.45-25.85) for the control group (P=0.09). A moderate negative correlation was found between PASI score and 25(OH)D levels (rs=-0.34; P=0.02). The serum levels of IL-17 (P=0.001), IL-23 (P=0.01) and IL-18 (P=0.02) were significantly higher in the patient group compared to controls. IL-17 concentrations were higher in patients with moderate to severe psoriasis compared to patients with mild psoriasis (P=0.003). No significant correlations were detected between the serum concentrations of 25(ОH)D and IL-17, IL-23, and IL-18. CONCLUSION: It was confirmed that IL-17 serum level is associated with psoriasis severity. Measurement of 25(OH)D serum concentration can be useful in patients with moderate to severe psoriasis with or without comorbidities. A direct association between 25(OH)D serum concentration and the serum concentrations of IL-17, IL-23, or IL-18 was not identified in this study.
- MeSH
- Adult MeSH
- Interleukin-17 * blood MeSH
- Interleukin-18 * blood MeSH
- Interleukin-23 * blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Psoriasis * blood MeSH
- Case-Control Studies MeSH
- Vitamin D * blood analogs & derivatives MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Branchioma is an uncommon benign neoplasm with an adult male predominance, typically occurring in the lower neck region. Different names have been used for this entity in the past (ectopic hamartomatous thymoma, branchial anlage mixed tumor, thymic anlage tumor, biphenotypic branchioma), but currently, the term branchioma has been widely accepted. Branchioma is composed of endodermal and mesodermal lineage derivatives, in particular epithelial islands, spindle cells, and mature adipose tissue without preexistent thymic tissue or evidence of thymic differentiation. Twenty-three branchiomas were evaluated morphologically. Eighteen cases with sufficient tissue were assessed by immunohistochemistry, next-generation sequencing (NGS) using the Illumina Oncology TS500 panel, and fluorescence in situ hybridization (FISH) using an RB1 dual-color probe. All cases showed a biphasic morphology of epithelial and spindle cells with intermingled fatty tissue. Carcinoma arising in branchioma was detected in three cases. The neoplastic cells showed strong AE1/3 immunolabeling (100%), while the spindle cells expressed CD34, p63, and SMA (100%); AR was detected in 40-100% of nuclei (mean, 47%) in 14 cases. Rb1 showed nuclear loss in ≥ 95% of neoplastic cells in 16 cases (89%), while two cases revealed retained expression in 10-20% of tumor cell nuclei. NGS revealed a variable spectrum of likely pathogenic variants (n = 5) or variants of unknown clinical significance (n = 6). Loss of Rb1 was detected by FISH in two cases. Recent developments support branchioma as a true neoplasm, most likely derived from the rudimental embryological structures of endoderm and mesoderm. Frequent Rb1 loss by immunohistochemistry and heterozygous deletion by FISH is a real pitfall and potential confusion with other Rb1-deficient head and neck neoplasms (i.e., spindle cell lipoma), especially in small biopsy specimens.
- MeSH
- Branchioma * pathology MeSH
- Adult MeSH
- In Situ Hybridization, Fluorescence MeSH
- Humans MeSH
- Molecular Biology MeSH
- Thymus Neoplasms * MeSH
- Neoplasms, Glandular and Epithelial * MeSH
- Soft Tissue Neoplasms * pathology MeSH
- Retinal Neoplasms * MeSH
- Retinoblastoma * genetics pathology MeSH
- Thymoma * MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Prevalence interních chorob zvyšující se s věkem je příčinou zvýšeného zastoupení seniorů mezi hospitalizovanými na lůžkách nechirurgických oborů. Nemoc, která je důvodem hospitalizace, u pacienta s diabetem obvykle rozkolísá glykemie. Řada vyšetřovacích metod vyžaduje přípravu se změnou příjmu a složení stravy, určitou dobu lačnění před výkonem či po něm. Toto vše zvyšuje riziko hypo/hyperglykemie. Ohrožuje zdraví i život pacienta. Prevencí je zejména frekventní monitorování glykemie. Přes pokročilý vývoj odběru a měření glykemie v kapilární krvi se jeví možnou pozitivní alternativou kontinuální měření glukózy senzorem. Proto jsme ihned po zprovoznění lůžek GIK využili možností, které nabízí Intermitentně skenované kontinuální měření glykemie (isCGM). Naše první zkušenosti s využitím isCGM u seniorů hospitalizovaných na GIK jsou velmi pozitivní. Při implementaci metody bylo překvapivým zjištěním, že ve vědecké literatuře není mnoho dostupných dat, která by hodnotila přínosy/rizika isCGM během běžné hospitalizace mimo JIP u pacientů vyžadujících časté monitorování glykemie.
The prevalence of internal diseases increasing with age is the reason for the increased number of seniors among those hospitalized in non-surgical beds. The disease that is the reason for hospitalization in a patient with diabetes usually fluctuates blood sugar. A number of examination methods require preparation with a change in intake and diet composition, a certain period of fasting before or after the procedure. All this increases the risk of hypo/hyperglycemia. It threatens the health and life of the patient. Prevention is especially frequent monitoring of blood glucose. Despite the advanced development of collection and measurement of glucose in capillary blood, continuous glucose measurement with a sensor appears to be a possible positive alternative. Therefore, immediately after the GIK beds were put into operation, we took advantage of the possibilities offered by Intermittently Scanned Continuous Glycemic Measurement (isCGM). Our first experiences with the use of isCGM in elderly patients hospitalized at GIK are very positive. When implementing the method, it was a surprising finding that there is not much data available in the scientific literature evaluating the benefits/risks of isCGM during routine non-ICU hospitalization in patients requiring frequent glycemic monitoring.
- MeSH
- Diabetes Mellitus * prevention & control MeSH
- Glycated Hemoglobin analysis MeSH
- Inpatients MeSH
- Continuous Glucose Monitoring * methods MeSH
- Blood Glucose analysis MeSH
- Humans MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Publication type
- Review MeSH
