| 1. |
- Affatato, Oreste, et al.
(författare)
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High efficacy of onabotulinumtoxinA treatment in patients with comorbid migraine and depression : a meta-analysis
- 2021
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Ingår i: Journal of Translational Medicine. - : Springer Nature. - 1479-5876. ; 19:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Migraine and depression are highly prevalent and partly overlapping disorders that cause strong limitations in daily life. Patients tend to respond poorly to the therapies available for these diseases. OnabotulinumtoxinA has been proven to be an effective treatment for both migraine and depression. While many studies have addressed the effect of onabotulinumtoxinA in migraine or depression separately, a growing body of evidence suggests beneficial effects also for patients comorbid with migraine and depression. The current meta-analysis systematically investigates to what extent onabotulinumtoxinA is efficient in migraineurs with depression.Methods: A systematic literature search was performed based on PubMed, Scopus and Web of Science from the earliest date till October 30th, 2020. Mean, standard deviation (SD) and sample size have been used to evaluate improvement in depressive symptoms and migraine using random- effects empirical Bayes model.Results: Our search retrieved 259 studies, eight of which met the inclusion criteria. OnabotulinumtoxinA injections administered to patients with both chronic migraine and major depressive disorder led to mean reduction of - 8.94 points (CI [ - 10.04,- 7.84], p < 0.01) in the BDI scale, of - 5.90 points (CI [ - 9.92,- 1.88], p < 0.01) in the BDI-II scale and of - 6.19 points (CI [ - 9.52,- 2.86], p < 0.01) in the PHQ-9 scale, when evaluating depressive symptoms. In the case of the migraine-related symptoms, we found mean reductions of - 4.10 (CI [ - 7.31,- 0.89], p = 0.01) points in the HIT6 scale, - 32.05 (CI [ - 55.96,- 8.14], p = 0.01) in the MIDAS scale, - 1.7 (CI [ - 3.27,- 0.13], p = 0.03) points in the VAS scale and of - 6.27 (CI [ - 8.48,- 4.07], p < 0.01) migraine episodes per month. Comorbid patients showed slightly better improvements in BDI, HIT6 scores and migraine frequency compared to monomorbid patients. The latter group manifested better results in MIDAS and VAS scores.Conclusion: Treatment with onabotulinumtoxinA leads to a significant reduction of disease severity of both chronic migraine and major depressive disorder in patients comorbid with both diseases. Comparative analyses suggest an equivalent strong effect in monomorbid and comorbid patients, with beneficial effects specifically seen for certain migraine features.
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| 2. |
- Al-Sabri, Mohamed H., et al.
(författare)
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Statins Induce Locomotion and Muscular Phenotypes in Drosophila melanogaster That Are Reminiscent of Human Myopathy : Evidence for the Role of the Chloride Channel Inhibition in the Muscular Phenotypes
- 2022
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 11:22
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Tidskriftsartikel (refereegranskat)abstract
- The underlying mechanisms for statin-induced myopathy (SIM) are still equivocal. In this study, we employ Drosophila melanogaster to dissect possible underlying mechanisms for SIM. We observe that chronic fluvastatin treatment causes reduced general locomotion activity and climbing ability. In addition, transmission microscopy of dissected skeletal muscles of fluvastatin-treated flies reveals strong myofibrillar damage, including increased sarcomere lengths and Z-line streaming, which are reminiscent of myopathy, along with fragmented mitochondria of larger sizes, most of which are round-like shapes. Furthermore, chronic fluvastatin treatment is associated with impaired lipid metabolism and insulin signalling. Mechanistically, knockdown of the statin-target Hmgcr in the skeletal muscles recapitulates fluvastatin-induced mitochondrial phenotypes and lowered general locomotion activity; however, it was not sufficient to alter sarcomere length or elicit myofibrillar damage compared to controls or fluvastatin treatment. Moreover, we found that fluvastatin treatment was associated with reduced expression of the skeletal muscle chloride channel, C1C-a (Drosophila homolog of CLCN1), while selective knockdown of skeletal muscle C1C-a also recapitulated fluvastatin-induced myofibril damage and increased sarcomere lengths. Surprisingly, exercising fluvastatin-treated flies restored C1C-a expression and normalized sarcomere lengths, suggesting that fluvastatin-induced myofibrillar phenotypes could be linked to lowered C1C-a expression. Taken together, these results may indicate the potential role of C1C-a inhibition in statinassociated muscular phenotypes. This study underlines the importance of Drosophila melanogaster as a powerful model system for elucidating the locomotion and muscular phenotypes, promoting a better understanding of the molecular mechanisms underlying SIM.
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| 3. |
- Amorim, Felippe E., et al.
(författare)
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Memory destabilization during reconsolidation : a consequence of homeostatic plasticity?
- 2021
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Ingår i: Learning & memory (Cold Spring Harbor, N.Y.). - : Cold Spring Harbor Laboratory Press (CSHL). - 1072-0502 .- 1549-5485. ; 28:10, s. 371-389
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Tidskriftsartikel (refereegranskat)abstract
- Remembering is not a static process: When retrieved, a memory can be destabilized and become prone to modifications. This phenomenon has been demonstrated in a number of brain regions, but the neuronal mechanisms that rule memory destabilization and its boundary conditions remain elusive. Using two distinct computational models that combine Hebbian plasticity and synaptic downscaling, we show that homeostatic plasticity can function as a destabilization mechanism, accounting for behavioral results of protein synthesis inhibition upon reactivation with different re-exposure times. Furthermore, by performing systematic reviews, we identify a series of overlapping molecular mechanisms between memory destabilization and synaptic downscaling, although direct experimental links between both phenomena remain scarce. In light of these results, we propose a theoretical framework where memory destabilization can emerge as an epiphenomenon of homeostatic adaptations prompted by memory retrieval.
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| 4. |
- Carneiro, Clarissa F. D., et al.
(författare)
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Comparing quality of reporting between preprints and peer-reviewed articles in the biomedical literature
- 2020
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Ingår i: RESEARCH INTEGRITY AND PEER REVIEW. - : BMC. - 2058-8615. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Preprint usage is growing rapidly in the life sciences; however, questions remain on the relative quality of preprints when compared to published articles. An objective dimension of quality that is readily measurable is completeness of reporting, as transparency can improve the reader's ability to independently interpret data and reproduce findings. Methods In this observational study, we initially compared independent samples of articles published in bioRxiv and in PubMed-indexed journals in 2016 using a quality of reporting questionnaire. After that, we performed paired comparisons between preprints from bioRxiv to their own peer-reviewed versions in journals. Results Peer-reviewed articles had, on average, higher quality of reporting than preprints, although the difference was small, with absolute differences of 5.0% [95% CI 1.4, 8.6] and 4.7% [95% CI 2.4, 7.0] of reported items in the independent samples and paired sample comparison, respectively. There were larger differences favoring peer-reviewed articles in subjective ratings of how clearly titles and abstracts presented the main findings and how easy it was to locate relevant reporting information. Changes in reporting from preprints to peer-reviewed versions did not correlate with the impact factor of the publication venue or with the time lag from bioRxiv to journal publication. Conclusions Our results suggest that, on average, publication in a peer-reviewed journal is associated with improvement in quality of reporting. They also show that quality of reporting in preprints in the life sciences is within a similar range as that of peer-reviewed articles, albeit slightly lower on average, supporting the idea that preprints should be considered valid scientific contributions.
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| 5. |
- de Ruijter, Markus J. T., et al.
(författare)
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Pipeline for automated assessment of intra- and inter-individual locomotive behavior in Drosophila melanogaster
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- While human psychology is studied extensively, a knowledge gap between psychology and neural physiology remains. Personality traits may be present in non-primate animals and are thought to have an evolutionary origin. Drosophila melanogaster are a highly used model organism due to their ease of culturing and handling. However, they have been little used for studying personality. In this article we describe a novel methodology that aims to assess locomotive individuality in Drosophila, as a first step into assessing potential personality traits. A dual experimental setup was performed where flies (N=40) were recorded six times, for five minutes, with ten minute breaks in between. In the first experimental setup, flies were aspirated back into a familiar vial containing food during the breaks. In the second setup, flies were kept in the recording arena for the whole duration of the experiment. Tracking of the Drosophila was performed using existing tracking software SLEAP. The resulting tracking data was subsequently examined for locomotion behavior as well as examined for more detailed behavioral motifs using B-SOiD. Finally, we assessed intra- and inter-fly differences based on the locomotion behavior. This setup resulted in an efficient experimental and computational pipeline capable of collecting and processing large amounts of high quality behavioral data. We show that the intra-individual differences are smaller than the inter-individual differences. The unsupervised clustering of behavioral motifs resulted in unusable clusters as they contained either multiple types of behavior, or were specific to individual recordings. We believe this pipeline may be of great use for studying behavioral patterns in Drosophila melanogaster in a broad manner and that combined experimental methods may start to reveal potential personalities in these organisms.
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| 6. |
- Johansson, Anton, et al.
(författare)
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Neurological manifestations of COVID-19 : A comprehensive literature review and discussion of mechanisms
- 2021
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Ingår i: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 358
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Forskningsöversikt (refereegranskat)abstract
- Several neurological symptoms and complications have been described in association with COVID-19, such as anosmia, ageusia, encephalitis and Guillain-Barre ' syndrome. Here, we review the literature describing SARSCoV-2-induced neurological manifestations and provide a comprehensive discussion of proposed mechanisms underlying the neurological pathophysiology. First, we analyse the neuroinvasiveness potential of the coronavirus family based on previous SARS-CoV-1 studies. Then, we describe the current evidence on COVID-19induced nervous tissue damage, including processes behind brain vasculopathy and cytokine storm. We also discuss in detail anosmia and Guillain-Barre ' syndrome. Finally, we provide a summarised timeline of the main findings in the field. Future perspectives are presented, and suggestions of further investigations to clarify how SARS-COV-2 can affect the CNS.
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| 7. |
- Lima da Cruz, Rafael Vitor, 1992-, et al.
(författare)
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A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus
- 2018
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Ingår i: Frontiers in Molecular Neuroscience. - : Frontiers Media SA. - 1662-5099. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The subgranular zone (SGZ) of dentate gyrus (DG) is one of the few regions in which neurogenesis is maintained throughout adulthood. It is believed that newborn neurons in this region encode temporal information about partially overlapping contextual memories. The 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring compound capable of inducing a powerful psychedelic state. Recently, it has been suggested that DMT analogs may be used in the treatment of mood disorders. Due to the strong link between altered neurogenesis and mood disorders, we tested whether 5-MeO-DMT is capable of increasing DG cell proliferation. We show that a single intracerebroventricular (ICV) injection of 5-MeO-DMT increases the number of Bromodeoxyuridine (BrdU+) cells in adult mice DG. Moreover, using a transgenic animal expressing tamoxifen-dependent Cre recombinase under doublecortin promoter, we found that 5 Meo-DMT treated mice had a higher number of newborn DG Granule cells (GC). We also showed that these DG GC have more complex dendritic morphology after 5-MeO-DMT. Lastly, newborn GC treated with 5-MeO-DMT, display shorter afterhyperpolarization (AHP) potentials and higher action potential (AP) threshold compared. Our findings show that 5-MeO-DMT affects neurogenesis and this effect may contribute to the known antidepressant properties of DMT-derived compounds.
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| 8. |
- Meth, Elisa, et al.
(författare)
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Association of Daily Eating Duration and Day-To-Day Variability in the Timing of Eating With Fatal Cancer Risk in Older Men
- 2022
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Ingår i: Frontiers in Nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Meal timing has significant effects on health. However, whether meal timing is associated with the risk of developing and dying of cancer is not well-researched in humans. In the present study, we used data from 941 community-dwelling men aged 71 years who participated in the Uppsala Longitudinal Study of Adult Men to examine the association of meal timing with cancer morbidity and fatal cancer. The following meal timing variables were derived from 7-day food diaries: (i) daily eating duration, i.e., the time between the first and last eating episode of an arbitrary day; (ii) the calorically weighted midpoint of the daily eating interval, a proxy of when the eating window typically occurs during an arbitrary day; and (iii) the day-to-day variability in the timing of eating. We also assessed the reported daily energy intake reliability using the Goldberg method. During a mean observational period of 13.4 years, 277 men (29.4%) were diagnosed with cancer. Furthermore, 191 men (20%) died from cancer during 14.7 years of follow-up. As shown by Cox regression adjusted for potential confounders (e.g., smoking status and daily energy intake), men with reliable dietary reports whose daily eating intervals were on average 13 h long had a 2.3-fold greater fatal cancer risk than men whose daily eating windows were on average about 11 h long. We also found that men with an average day-to-day variability in the timing of eating of 48 to 74 min had a 2- to 2.2-fold higher fatal cancer risk than those with the lowest average day-to-day variability in the timing of eating (i.e., 23 min). No clear associations were found in men with inadequate dietary reports, emphasizing the need to consider the reliability of dietary records in nutritional epidemiology. To fully unlock its potential, studies are needed to test whether recommendations to time-restrict the 24-h eating interval and reduce day-to-day variability in the timing of eating can meaningfully alter the risk of death due to cancer.
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| 9. |
- Mohamed, Mohamed S., et al.
(författare)
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Sex differences in COVID-19 : the role of androgens in disease severity and progression
- 2021
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Ingår i: Endocrine. - : Springer Nature. - 1355-008X .- 1559-0100. ; 71:1, s. 3-8
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Forskningsöversikt (refereegranskat)abstract
- Purpose Throughout the SARS-CoV2 pandemic, multiple reports show higher percentages of hospitalization, morbidity, and mortality among men than women, indicating that men are more affected by COVID-19. The pathophysiology of this difference is yet not established, but recent studies suggest that sex hormones may influence the viral infectivity process. Here, we review the current evidence of androgen sensitivity as a decisive factor for COVID-19 disease severity. Methods Relevant literature investigating the role of androgens in COVID-19 was assessed. Further, we describe several drugs suggested as beneficial for COVID-19 treatment related to androgen pathways. Lastly, we looked at androgen sensitivity as a predictor for COVID-19 progression and ongoing clinical trials on androgen suppression therapies as a line of treatment. Results SARS-COV2 virus spike proteins utilize Transmembrane protease serine 2 (TMPRSS2) for host entry. Androgen receptors are transcription promoters for TMPRSS2 and can, therefore, facilitate SARS-COV2 entry. Variants in the androgen receptor gene correlate with androgen sensitivity and are implicated in diseases like androgenetic alopecia and prostate cancer, conditions that have been associated with worse COVID-19 outcomes and hospitalization. Conclusion Androgen's TMPRSS2-mediated actions might explain both the low fatalities observed in prepubertal children and the differences between sexes regarding SARS-COV2 infection. Androgen sensitivity may be a critical factor in determining COVID-19 disease severity, and sensitivity tests can, therefore, help in predicting patient outcomes.
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