Αναζήτηση αυτού του ιστολογίου

Τετάρτη 4 Ιανουαρίου 2023

Are psychedelics the answer to chronic pain: a review of current literature

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Abstract

Chronic pain is a common and complex problem, with an unknown etiology. Psychedelics like lysergic acid diethylamide (LSD) and psilocybin, may play a role in the management of chronic pain. Through activation of the serotonin-2A (5-HT2A) receptor, several neurophysiological responses result in the disruption of functional connections in brain regions associated with chronic pain. Healthy reconnections can be made through neuroplastic effects, resulting in sustained pain relief. However, this process is not fully understood and evidence of efficacy is limited and of low quality. In cancer and palliative related pain, the analgesic potential of psychedelics was established decades ago, and the current literature shows promising results on efficacy and safety in patients with cancer-related psychological distress. In other areas, patients suffering from severe headache disorders like migraine and cluster headache who have self-medicated with psychedelics report both acute and prophylactic efficacy of LSD and psilocybin. Randomized control trials are now being conducted to study the effects in cluster headache Furthermore, psychedelics have a generally favorable safety profile especially when compared to other analgesics like opioids. In addition, psychedelics do not have the addictive potential of opioids. Given the current epidemic use of opioids, and that patients are in desperate need of an alternative treatment, it is important that further research is conducted on the efficacy of psychedelics in chronic pain conditions.

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Editorial perspective: Leaving the baby in the bathwater in neurodevelopmental research

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Neurodevelopmental conditions are characterised by differences in the way children interact with the people and environments around them. Despite extensive investigation, attempts to uncover the brain mechanisms that underpin neurodevelopmental conditions have yet to yield any translatable insights. We contend that one key reason is that psychologists and cognitive neuroscientists study brain function by taking children away from their environment, into a controlled lab setting. Here, we discuss recent research that has aimed to take a different approach, moving away from experimental control through isolation and stimulus manipulation, and towards approaches that embrace the measurement and targeted interrogation of naturalistic, user-defined and complex, multivariate datasets. We review three worked examples (of stress processing, early activity level in ADHD and social brain development in autism) to illustrate how these new approaches might lead t o new conceptual and translatable insights into neurodevelopment.

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Contribution of genotypes in Prothrombin and Factor V Leiden to COVID‐19 and disease severity in patients at high risk for hereditary thrombophilia

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abstract

Aim

Thrombotic and microangiopathic effects have been reported in COVID-19 patients. This study examined the contribution of the hereditary thrombophilia factors Prothrombin (FII) and Factor V Leiden (FVL) genotypes to the severity of COVID-19 disease and the development of thrombosis.

Methods

This study investigated FII and FVL alleles in a cohort of 9508 patients (2606 male and 6902 female) with thrombophilia. It was observed that 930 of these patients had been infected by SARS-CoV-2 causing COVID-19. The demographic characteristics of the patients and their COVID-19 medical history were recorded. Detailed clinical manifestations were analyzed in a subset of cases (n=4092). This subgroup was age and gender matched. FII and FVL frequency data of healthy populations without thrombophilia risk were obtained from Bursa Uludag University Medical Genetic Department's Exome Databank.

Results

The ratio of males (31.08%; 27.01%) and the mean age (36.85 ±15.20; 33.89±14.14) were higher among COVID-19 patients compared to non-COVID-19 patients. The prevalence of FVL and computerized tomography (CT) positivity in COVID-19 patients was statistically significant in the thrombotic subgroup (p<0.05). FVL prevalence, CT positivity rate, history of thrombosis, and Pulmonary thromboembolism complication were found to be higher in deceased COVID-19 patients (p<0.05). Disease severity was mainly affected by Factor V Leiden and not related to genotypes at the Prothrombin mutations.

Conclusion

Overall, disease severity and development of thrombosis in COVID-19 are mainly affected by the variation within the FVL gene. Possible FVL mutation should be investigated in COVID-19 patients and appropriate treatment should be started earlier in FVL-positive patients.

This article is protected by copyright. All rights reserved.

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Integrative systems immunology uncovers molecular networks of the cell cycle that stratify COVID‐19 severity

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Abstract

Several perturbations in the number of peripheral blood leukocytes, such as neutrophilia and lymphopenia associated with Coronavirus disease 2019 (COVID-19) severity, point to systemic molecular cell cycle alterations during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, the landscape of cell cycle alterations in COVID-19 remains primarily unexplored. Here, we performed an integrative systems immunology analysis of publicly available proteome and transcriptome data to characterize global changes in the cell cycle signature of COVID-19 patients. We found significantly enriched cell cycle-associated gene co-expression modules and an interconnected network of cell cycle-associated differentially expressed proteins (DEPs) and genes (DEGs) by integrating the molecular data of 1,469 individuals (981 SARS-CoV-2 infected patients and 488 controls [either healthy controls or individuals with other respiratory illnesses]). Among these DEPs and DEGs are seve ral cyclins (CCNs), cell division cycles (CDCs), cyclin-dependent kinases (CDKs), and mini-chromosome maintenance (MCMs) proteins. COVID-19 patients partially shared the expression pattern of some cell cycle-associated genes with other respiratory illnesses but exhibited some specific differential features. Notably, the cell cycle signature predominated in the patients' blood leukocytes (B, T, and NK cells) and was associated with COVID-19 severity and disease trajectories. These results provide a unique global understanding of distinct alterations in cell cycle-associated molecules in COVID-19 patients, suggesting new putative pathways for therapeutic intervention.

This article is protected by copyright. All rights reserved.

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Birth weight, gestational age and risk of cardiovascular disease in early adulthood: Influence of familial factors

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Abstract
The association between intrauterine growth restriction (IUGR) and cardiovascular disease (CVD) later in life might be confounded by familial factors. We conducted a bi-national register-based cohort study to assess associations of birthweight for gestational age (GA), a proxy for IUGR, and GA with CVD risk in early adulthood, before and after addressing familial factors via sibling comparison. We included 3,410,334 live non-malformed singleton births in Sweden (1973-1996) and Denmark (1978-1998). During a median follow-up of 10 years from age 18 onwards, 29,742 individuals developed incident CVD (hypertensive, ischemic heart, and cerebrovascular diseases). Compared with individuals born with appropriate birthweight for GA (AGA, 10th-90th percentiles) or full term (39-40 gestational weeks), individuals born severely small for GA (SGA, <3rd percentile) or preterm (22-36 weeks) were at increased risk of CVD [HRs (95% CIs): 1.38 (1.32-1.45) and 1 .31 (1.25-1.38), respectively]. The association was attenuated when comparing individuals born SGA with their AGA siblings (1.11, 0.99-1.25), but remained robust when comparing individuals born preterm with their term siblings (1.21, 1.07-1.37). Our findings suggest that both SGA and preterm birth are associated with CVD risk in early adulthood, with greater familial confounding noted for SGA.
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Τρίτη 3 Ιανουαρίου 2023

Mutation-associated transcripts reconstruct the prognostic features of oral tongue squamous cell carcinoma

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International Journal of Oral Science, Published online: 03 January 2023; doi:10.1038/s41368-022-00210-3

Mutation-associated transcripts reconstruct the prognostic features of oral tongue squamous cell carcinoma
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Automating the treatment planning process for 3D‐conformal pediatric craniospinal irradiation therapy

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Abstract

Purpose

Pediatric patients with medulloblastoma in low- and middle-income countries (LMICs) are most treated with 3D-conformal photon craniospinal irradiation (CSI), a time-consuming, complex treatment to plan, especially in resource-constrained settings. Therefore, we developed and tested a 3D-conformal CSI autoplanning tool for varying patient lengths.

Methods and materials

Autocontours were generated with a deep learning model trained:tested (80:20 ratio) on 143 pediatric medulloblastoma CT scans (patient ages: 2–19 years, median = 7 years). Using the verified autocontours, the autoplanning tool generated two lateral brain fields matched to a single spine field, an extended single spine field, or two matched spine fields. Additional spine subfields were added to optimize the corresponding dose distribution. Feathering was implemented (yielding nine to 12 fields) to give a composite plan. Each planning approach was tested on six patients (ages 3–10 years). A pediatric radiation oncologist assessed clinical acceptability of each autoplan.

Results

The autocontoured structures' average Dice similarity coefficient ranged from .65 to .98. The average V95 for the brain/spinal canal for single, extended, and multi-field spine configurations was 99.9% ± 0.06%/99.9% ± 0.10%, 99.9% ± 0.07%/99.4% ± 0.30%, and 99.9% ± 0.06%/99.4% ± 0.40%, respectively. The average maximum dose across all field configurations to the brainstem, eyes (L/R), lenses (L/R), and spinal cord were 23.7 ± 0.08, 24.1 ± 0.28, 13.3 ± 5.27, and 25.5 ± 0.34 Gy, respectively (prescription = 23.4 Gy/13 fractions). Of the 18 plans tested, all were scored as clinically acceptable as-is or clinically acceptable with minor, time-efficient edits preferred or required. No plans were scored as clinically unacceptable.

Conclusion

The autoplanning tool successfully generated pediatric CSI plans for varying patient lengths in 3.50 ± 0.4 minutes on average, indicating potential for an efficient planning aid in a resource-constrained settings.

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Promising applications of human-derived saliva biomarker testing in clinical diagnostics

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International Journal of Oral Science, Published online: 04 January 2023; doi:10.1038/s41368-022-00209-w

Promising applications of human-derived saliva biomarker testing in clinical diagnostics
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Temporal Trends in Variability of Respirable Dust and Respirable Quartz Concentrations in the European Industrial Minerals Sector

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Abstract
While between- and within-worker variability have been studied quite extensively, hardly any research is available that examines long-term trends in the variability of occupational exposure. In this first study on trends in occupational exposure variability temporal changes in the variability of respirable dust and respirable quartz concentrations within the European industrial minerals sector were demonstrated. Since 2000 the European Industrial Minerals Association's Dust Monitoring Program (IMA-DMP) has systematically collected respirable dust and respirable quartz measurements. The resulting IMA-DMP occupational exposure database contains at present approximately 40 000 personal full-shift measurements, collected at 177 sites owned by 39 companies, located in 23 European countries. Repeated measurements of workers performing their duties within a specific site-job-campaign combination allowed estimation of within- and between-worker variabi lity in exposure concentrations. Overall day-to-day variability predominated the between-worker variability for both respirable dust concentrations and quartz concentrations. The within-worker variability in concentrations by job was two to three times higher for respirable quartz than for respirable dust. The median between-worker variability in respirable dust concentrations was low and further reduced over time. For quartz concentrations the same phenomenon albeit somewhat less strong was observed. In contrast, for the within-worker variability in concentrations downward and upward temporal trends were apparent for both respirable dust and respirable quartz. The study shows that the (relative) size of temporal variability is large and unpredictable and therefore regular measurement campaigns are needed to ascertain compliance to occupational exposure limit values.
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Δευτέρα 2 Ιανουαρίου 2023

Deferoxamine mesylate enhances mandibular advancement‐induced condylar osteogenesis by promoting H‐type angiogenesis

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

The effect of functional orthopedic treatment for mandibular deficiency relies on mandibular advancement (MA)-induced condylar new bone formation. However, this is not easy to achieve, especially in non-growing patients. Therefore, how to obtain reliable MA-induced condylar osteogenesis is much worthy of studying.

Objective

To investigate whether deferoxamine mesylate (DFM) enhances MA-induced condylar osteogenesis in middle-aged mice.

Methods

Forty 30-week-old male C57BL/6J mice were randomly divided into 4 groups: the control (Ctrl), DFM, MA+Ctrl, and MA+DFM groups. After a 4-week experimental period, femurs, tibias, and condyles were collected for morphological, micro-computed tomography, and histological evaluation.

Results

For long bones, DFM reversed osteoporosis in middle-aged mice by promoting H-type angiogenesis. For mandibular condyles, MA promoted condylar osteogenesis in middle-aged mice, thereby allowing the mandible to achieve a stable protruding position. In addition, DFM enhanced the volume and quality of MA-induced condylar new bone formation. Furthermore, histological analysis revealed that DFM enhanced MA-induced condylar subchondral ossification. Mechanistically, it was confirmed that DFM increased the number of H-type vessels and their coupled Osterix+ osteoprogenitors by up-regulating the hypoxia-inducible factor (HIF)-1α signaling pathway, thereby enhancing MA-induced condylar osteogenesis.

Conclusion

Applying DFM to enhance MA-induced condylar osteogenesis through H-type angiogenesis is expected to be an effective strategy to achieve favorable functional orthopedic treatment effectiveness in non-growing patients.

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