Comparative analysis of the time-dependent functional and molecular changes in spinal cord degeneration induced by the G93A SOD1 gene mutation and by mechanical compression

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The human G93A-SOD1 mutation in a pre-symptomatic rat model of amyotrophic lateral sclerosis increases the vulnerability to a mild spinal cord compression

<p>Abstract</p> <p>Background</p> <p>Traumatic injuries can undermine neurological functions and act as risk factors for the development of irreversible and fatal neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). In this study, we have investigated how a mutation of the superoxide dismutase 1 (SOD1) gene, linked to the development of ALS, modifies the acute response to a gentle mechanical compression of the spinal cord. In a 7-day post-injury time period, we have performed a comparative ontological analysis of the gene expression profiles of injured spinal cords obtained from pre-symptomatic rats over-expressing the G93A-SOD1 gene mutation and from wild type (WT) littermates.</p> <p>Results</p> <p>The steady post-injury functional recovery observed in WT rats was accompanied by the early activation at the epicenter of injury of several growth-promoting signals and by the down-regulation of intermediate neurofilaments and of genes involved in the regulation of ion currents at the 7 day post-injury time point. The poor functional recovery observed in G93A-SOD1 transgenic animals was accompanied by the induction of fewer pro-survival signals, by an early activation of inflammatory markers, of several pro-apoptotic genes involved in cytochrome-C release and by the persistent up-regulation of the heavy neurofilament subunits and of genes involved in membrane excitability. These molecular changes occurred along with a pronounced atrophy of spinal cord motor neurones in the G93A-SOD1 rats compared to WT littermates after compression injury.</p> <p>Conclusions</p> <p>In an experimental paradigm of mild mechanical trauma which causes no major tissue damage, the G93A-SOD1 gene mutation alters the balance between pro-apoptotic and pro-survival molecular signals in the spinal cord tissue from the pre-symptomatic rat, leading to a premature activation of molecular pathways implicated in the natural development of ALS.</p

How the COVID-19 pandemic affects transgender health care in upper-middle-income and high-income countries – A worldwide, cross-sectional survey

Background Since the beginning of the COVID-19 pandemic, access to medical care was restricted for nearly all non-acute medical conditions. Due to their status as a vulnerable social group and the inherent need for transition-related treatments (e.g., hormone treatment), transgender people are assumed to be affected particularly severely by the restrictions caused by the COVID-19 pandemic. This study aims to assess the impact of the COVID-19 pandemic on the health and health care of transgender people. Methods and findings As an ad hoc collaboration between researchers, clinicians, and 23 community organizations, we developed a web-based survey. The survey was translated into 26 languages, and participants were recruited via various social media and LGBTIQ-community sources. Recruitment started in May 2020. We assessed demographical data, physical and mental health problems (e.g., chronic physical conditions), risk factors (e.g., smoking), COVID-19 data (symptoms, contact history, knowledge and concerns about COVID-19), and the influence of the COVID-19 pandemic on access to transgender health care and health-related supplies. To identify factors associated with the experience of restrictions to transgender health care, we conducted multivariate logistic regression analysis. 5267 transgender people from 63 higher-middle income and high-income countries participated in the study. Over 50% of the participants had risk factors for a severe course of a COVID-19 infection and were at a high risk of avoiding testing or treatment of a COVID-19 infection due to the fear of mistreatment or discrimination. Access to transgender health care services was restricted due to the COVID-19 pandemic for 50% of the participants. Male sex assigned at birth and a lower monthly income were significant predictors for the experience of restrictions to health care. 35.0% of the participants reported at least one mental health conditions. Every third participant had suicidal thoughts, and 3.2% have attempted suicide since the beginning of the COVID-19 pandemic. A limitation of the study is that we did not analyze data from low-income countries and access to the internet was necessary to participate. Conclusions Transgender people are assumed to suffer under the severity of the pandemic even more than the general population due to the intersections between their status as a vulnerable social group, their high amount of medical risk factors, and their need for ongoing medical treatment. The COVID-19 pandemic can potentiate these vulnerabilities, add new challenges for transgender individuals, and, therefore, can lead to devastating consequences, like severe physical or mental health issues, self-harming behaviour, and suicidality

How the COVID-19 pandemic affects transgender health care - A cross-sectional online survey in 63 upper-middle-income and high-income countries

Background Due to the COVID-19 pandemic, access to medical care is restricted for nearly all non-acute conditions. Due to their status as a vulnerable social group and the inherent need for transition-related treatments, transgender people are assumed to be affected particularly severely by the restrictions caused by the COVID-19 pandemic. Methods As an ad hoc collaboration between researchers, clinicians and 23 community organizations, we developed a web-based survey in German that was translated into 26 languages. Participants were recruited via community sources, social media channels, and snowball sampling since May 2020. The present sample is based on the data collected until August 9, 2020. We assessed demographical data, health problems, risk factors, COVID-19 data (e.g., contact history), and the influence of the COVID-19 pandemic on access to transgender health care services. To identify factors associated with the experience of restrictions, we conducted multiple logistic regression analysis. Results 5267 transgender people from 63 upper-middle-income and high-income countries participated in the study. Over 50% of the participants had risk factors for a severe course of a COVID-19 infection and were at a high risk of avoiding COVID-19 treatment due to the fear of mistreatment or discrimination. Access to transgender health care services was restricted for 50% of the participants. Male sex assigned at birth and a lower monthly income were significant predictors for the experience of restrictions to health care. 35.0% reported at least one mental health condition and 3.2% have attempted suicide since the beginning of the COVID-19 pandemic. Discussion Transgender people suffer under the severity of the pandemic due to the intersections between their status as a vulnerable social group, their high number of medical risk factors, and their need for ongoing medical treatment. The COVID-19 pandemic can potentiate these vulnerabilities, add new challenges for transgender people, and, therefore, can lead to devastating consequences, like severe physical or mental health issues, self-harming behavior, and suicidality

Etude du rôle de nogo dans la sclérose latérale amyotrophique (Validation d'un marqueur moléculaire)

La Sclérose Latérale Amyotrophique (SLA) est une maladie neurodégénérative caractérisée par une atteinte des motoneurones de la moelle épinière, du tronc cérébral et du cortex moteur. L'objectif de cette thèse a été d'identifier et d'analyser les mécanismes cellulaires et moléculaires aboutissant à la perte des motoneurones. Pour cela, nous avons poursuivi les recherches menées au laboratoire sur le gène nogo, inhibiteur reconnu de la régénérescence axonale, et identifié comme marqueur potentiel de la SLA. Les différentes isoformes de Nogo présentent un profil d'expression caractéristique dans le muscle des patients atteints de SLA. Nous avons montré que les niveaux protéiques de Nogo-A et Nogo-B sont corrélés à l'état fonctionnel du patient ainsi qu'à la surface des fibres oxydatives. Nos études immunohistochimiques montrent une localisation quasi exclusive de Nogo-A dans les fibres oxydatives atrophiques de patients atteints de SLA. Ceci suggère que le niveau d'expression de Nogo-A et Nogo-B constitue un marqueur moléculaire de la sévérité de la maladie. Afin de caractériser la fonction de Nogo-A au cours de la pathologie, nous avons croisé les souris G86R (modèle transgenique de la SLA) avec des souris invalidées pour le gène Nogo-A (Nogo-A-/-). Les souris G86R/Nogo-A-/- ont présenté une augmentation significative de la durée de vie par rapport aux souris G86R/NogoA+/+. Afin de déterminer si la seule expression musculaire de Nogo-A, telle que nous la détectons chez les patients atteints de SLA et les souris G86R, est suffisante pour provoquer une déstabilisation de la jonction neuromusculaire, nous avons réalisé des expériences de transfection in vivo en injectant un vecteur d'expression Nogo-A dans le muscle. Les résultats de ces études montrent que la morphologie de la jonction neuromusculaire est affectée par l'expression ectopique de Nogo-A. En conclusion, ce travail de thèse suggère que le muscle participe activement au développement d'une SLA.Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of motor neurons in the spinal cord, brain stem and motor cortex. The objective of my PhD was to analyse the cellular and molecular mechanisms implicated in the loss of motor neurons. In this context, we carried out the studies conducted in our laboratory on the neurite outgrowth inhibitor Nogo identified as potential marker of ALS disease. Different isoforms of Nogo exhibit a specific pattern of expression in the muscle biopsies of ALS patients. Our studies showed that the protein levels of Nogo-A and Nogo-B correlated with the severity of clinical disability and with the mean area of oxidative fibres. In addition, the Nogo-A immunoreactivity was observed selectively in atrophic oxidative muscle fibres of ALS patients. These results suggest that Nogo-A and Nogo-B are the markers of disease severity. In order to characterise the function of Nogo-A in the pathology we crossbred the G86R ALS transgenic mice with the Nogo-A (Nogo-A-/-) knock-out mice. The life span G86R/ Nogo-A-/-was significantly increased. In order to determine if the muscular expression of Nogo-A as we observed in the muscle biopsies of ALS patients and in the muscle of G86R mice was sufficient to provoke destabilisation of neuromuscular junction (NMJ), we performed electrotransfer of a plasmid carrying Nogo-A gene into the soleus muscle of wild type mice. We observed that the morphology of the NMJ was affected by ectopic expression of Nogo-A. In conclusion, our results suggest that the muscle participates to the development of ALS.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Relationship between epistemological beliefs and motivational orientation among high school students

Relationship between epistemological beliefs and motivational orientation of high school students was studied and their relationship with school majoring, GPA and gender. To estimate epistemological beliefs and motivational orientation Schommer's Epistemological Questionnaire (EQ) and Work Preference Inventory (WPI) were used. Through factor analysis of EQ 5 factors were extracted, that differ from those Schommer singled out. Negative correlation between naive epistemological beliefs on one side, and intrinsic (-0.327, p lt 0.01) and general motivation (-0.247, p lt 0.01) on the other, was determined. Students majoring in social sciences have more mature epistemological beliefs (F=11.278, df=1, p lt 0.01. Boys have more mature epistemological beliefs than girls only on factor Avoiding relating, ambiguity and dependence on authority (F=16.899, df=1, p lt 0.01). Correlation between epistemological beliefs and GPA was not determined. Students majoring in social sciences have higher level of motivation (F=6.626, df=1, p lt 0.05). Girls are more motivated by enjoying in what they are doing (F=6.261, df=1, p lt 0.05)

Cyberchondria in the age of COVID-19

The global epidemic of (mis)information, spreading rapidly via social media platforms and other outlets, can be a risk factor for the development of anxiety disorders among vulnerable individuals. Cyberchondria can be a vulnerability factor for developing anxiety in a pandemic situation, particularly when the Internet is flooded with (mis)information. The aim of our study was to examine how cyberchondria is related to changes in levels of COVID-19 concern and safety behaviours among persons living in Croatia during the period in which the first COVID-19 case was identified and when the country recorded its first fatality. Repeated cross-sectional data collection was conducted during two waves over a period of three weeks (N1 = 888; N2 = 966). The first began on the day of the first confirmed case of COVID-19 in Croatia (February 24th, 2020) and the second wave began three weeks later, on the day the first COVID-19 fatality was recorded in Croatia (March 19th, 2020). Participants completed an online questionnaire regarding various COVID-19 concerns and safety behaviours aimed at disease prevention (information seeking, avoidance and hygiene) and a measure of cyberchondria (Short Cyberchondria Scale, SCS). We analysed whether changes to the epidemiological situation during the period between the two waves of data collection led to an increase in COVID-19 related behaviour directly and indirectly via an increase in COVID-19 concerns. The results indicated that, between the two waves of research, there was a pronounced increase in concerns regarding COVID-19 (b = 1.11, p < .001) as well as significant behavioural changes (b = 1.18–2.34, p < .001). Also, results demonstrated that cyberchondria plays a moderating role in these changes. In the first wave, persons with severe cyberchondria were already intensely concerned with safety behaviours. High cyberchondria and high levels of concern about the COVID-19 are associated with intense avoidance behaviours, R2 = .63, p < .001. A moderated partial mediation model was confirmed, in which the effect of the epidemiological situation was weaker for those with higher results on the SCS (as indicated by index of moderated mediation between -.10 and -.15, p < .05). As such, cyberchondria is a contributing factor to long-term anxiety and its impact during pandemic on the general mental health burden should therefore be further investigated

The Use of Probiotics in Dental Medicine

The term probiotic was first used in 1965. And it literally holds a meaning “for life” to describe “a matter that microorganisms secret to stimulate the growth of other” thus giving the contrast to the term antibiotics. Probiotics are living microorganisms which reside in gastrointestinal and urogenital mucosa that benefit the health and boost vitality. Most commonly used genera of bacteria are Lactobacillus and Bifidobacteriae. The probiotics most recognized role is in restoring the balance in oral microflora in the situation when pathogen species of bacteria start to surmount. They accomplish that by competing for the adherent space, and for the source of food with pathogen bacteria and by changing oral cavity conditions. Also, they possess antimicrobial and imunomodifying characteristics. They prove great results fighting periodontal disease, halitosis, candidiasis as well as in preventing caries. Most of commerically available genera of probiotics (yogurt, milk shakes, pills etc.) are considered safe, but there is a certain part of population at risk