Closed-loop recruitment of striatal parvalbumin interneurons prevents the onset of compulsive behaviors

A prominent electrophysiological feature of compulsive behaviours is striatal hyperactivity; but its underlying dysfunctional cellular mechanisms still need to be characterized. Within the striatum, parvalbumin-positive interneurons (PVI) exert a powerful feedforward inhibition essential for the regulation of striatal activity. To investigate the potential implication of striatal PVI in aberrant repetitive behaviors, we used the Sapap3 mutant mice which exhibit compulsive-like behaviours characterized by excessive self-grooming. When striatal PVI in the centromedial striatum of Sapap3 mice were we optogenetically activated, we first showed that the number of compulsive-like events were greatly reduced. To investigate further the critical time-window when striatal PVI needed to be recruited for the behavioural regulation of compulsive-like grooming, we then designed a novel closed-loop stimulation pipeline. We identified a transient 1-4 Hz oscillations in the orbitofrontal cortex that temporally predicted grooming onsets. Exploiting this delta band signal as a biomarker, we were able to provide on-demand stimulation of striatal PVI shortly before predicted grooming events. This targeted closed-loop optogenetics approach greatly reduced grooming events and demonstrated that the recruitment of striatal PVI regulated the initiations of compulsive-like behaviours.

Antiherpetic drugs: a potential way to prevent Alzheimer’s disease?

Background Considering the growing body of evidence suggesting a potential implication of herpesviruses in the development of dementia, several authors have questioned a protective effect of antiherpetic drugs (AHDs) which may represent a new means of prevention, well tolerated and easily accessible. Subsequently, several epidemiological studies have shown a reduction in the risk of dementia in subjects treated with AHDs, but the biological plausibility of this association and the impact of potential methodological biases need to be discussed in more depth. Methods Using a French medico-administrative database, we assessed the association between the intake of systemic AHDs and the incidence of (i) dementia, (ii) Alzheimer’s disease (AD), and (iii) vascular dementia in 68,291 subjects over 65 who were followed between 2009 and 2017. Regarding potential methodological biases, Cox models were adjusted for numerous potential confounding factors (including proxies of sociodemographic status, comorbidities, and use of healthcare) and sensitivity analyses were performed in an attempt to limit the risk of indication and reverse causality biases. Results 9.7% of subjects (n=6642) had at least one intake of systemic AHD, and 8883 incident cases of dementia were identified. Intake of at least one systemic AHD during follow-up was significantly associated with a decreased risk of AD (aHR 0.85 95% confidence interval [0.75–0.96], p=0.009) and, to a lesser extent with respect to p values, to both dementia from any cause and vascular dementia. The association with AD remained significant in sensitivity analyses. The number of subjects with a regular intake was low and prevented us from studying its association with dementia. Conclusions Taking at least one systemic AHD during follow-up was significantly associated with a 15% reduced risk of developing AD, even after taking into account several potential methodological biases. Nevertheless, the low frequency of subjects with a regular intake questions the biological plausibility of this association and highlights the limits of epidemiological data to evaluate a potential protective effect of a regular treatment by systemic AHDs on the incidence of dementia

Rapidly Progressive Pituitary Apoplexy in a Patient with COVID-19 Disease Treated with Endoscopic Endonasal Surgery

This report describes a case of pituitary apoplexy with rapidly evolving hemorrhage in a 74-year-old female with coronavirus disease 2019 (COVID-19) disease. The patient presented with severe headache and mild respiratory symptoms, with laboratories concerning for pituitary hypofunction. Brain imaging demonstrated a sellar mass concerning for a pituitary adenoma with ischemic apoplexy. She subsequently developed visual deficits within 24 hours of presentation, and repeat imaging demonstrated evolving hemorrhage and new mass effect on the optic chiasm. She was successfully managed with urgent endoscopic endonasal surgery despite her COVID-19 positive status by taking special intraoperative precautions to mitigate SARS-CoV2 transmission risk. Only a handful of cases of pituitary apoplexy have been reported in association with COVID-19 disease, and even fewer reports exist of endonasal procedures in such cases. We discuss the potential implication of COVID-19 in the occurrence of pituitary apoplexy, in addition to the safety and success of endonasal surgery in this population.

Syndecan-1 is overexpressed in human thoracic aneurysm but is dispensable for the disease progression in vivo

Glycosaminoglycans (GAGs) pooling has been considered since long as one of the histopathological characteristics defining thoracic aortic aneurysm (TAA) together with smooth muscle cells (SMCs) apoptosis and elastin fibers degradation. However, few information is provided about GAGs composition or potential implication in TAA pathology. Syndecan-1 (Sdc-1) is a heparan sulfate proteoglycan that is implicated in extracellular matrix (ECM) interaction and assembly, regulation of SMCs phenotype and various aspects of inflammation in the vascular wall. In the current work, the regulation of Sdc-1 protein was examined in human TAA by ELISA and immunohistochemistry. In addition, the role of Sdc-1 was evaluated in descending TAA in vivo using a mouse model combining both aortic wall weakening and hypertension. Our results showed that Sdc-1 protein is over expressed in human TAA aortas compared to healthy counterparts and that SMCs are the major cell type expressing Sdc-1. Similarly, in the mouse model used, Sdc-1 expression was increased in TAA aortas compared to healthy samples. Although its protective role against abdominal aneurysm has been reported, we observed that Sdc-1 was dispensable for TAA prevalence or rupture. In addition, Sdc-1 deficiency did not alter the extent of aortic wall dilatation, elastin degradation, collagen deposition, or leukocyte recruitment in our TAA model. These findings suggest that Sdc-1 could be a biomarker revealing TAA pathology. Future investigations could uncover the underlying mechanisms leading to Sdc-1 expression alteration in TAA.

Role of Governance and Public Trust on Government Debt-Economic Growth Nexus (A Global Empirical Analysis)

High government debts in several countries have the potential to trigger or exacerbate economic instability. These concerns are consistent with the results of this study, where countries that have a high debt ratio tend to have declining economic growth. To provide more understanding about this effect, this study tries to examine the effect of debt on economic growth by utilising the governance and public trust level as a contextual variable and mediator. Empirically, both variables have a prominent role in the debt and economic growth nexus. The debt threshold as a budgetary rule is necessary but might not be sufficient to validate the rationality of rising debt. The capability of government in providing public governance and the effect of additional debt on public trust is another crucial aspect that needs to be seriously scrutinised, or when the addition of debt becomes inevitable (such as in pandemic situation), the government should strengthen governance capability to ensure the productivity of debt and mitigate the decreased public trust. This finding implies that the debt policy should not only be based on budgetary rule but also the capacity of governance and the potential implication of the falling public trust.

No Impact of Psychosocial Stress on Glioblastoma Development

Purpose: Psychosocial stress represents an important source of questions in the potential implication of origin of cancer. The aim of the study was to assess stress prevalence prior to diagnosis of wild-type IDH glioblastoma.Methods: This prospective single-center study enrolled consecutive new cases of wild-type IDH glioblastoma diagnosed between December 2019 and March 2021 at the University Hospital of Bordeaux. A standardized patient self-assessment stress questionnaire explored both the presence of stressor exposure and the intensity of patient stress level prior to the diagnosis. Four groups were included: high stressors/high stress, high stressors/low stress, low stressors/low stress, and low stressors/high stress. Patient characteristics were collected. Statistical analysis was based on the Chi-square test and the Kaplan-Meier survival estimator.Results: Sixty-four patients with a median age of 66 years were included. Glioblastoma involved predominantly the frontal lobe (39%). Thirty-six patients (56.3%) presented a low stressor/low stress profile. Stress corresponded mainly to the death of a loved one or to family health problems. Among working professionals, 20 patients (67.5%) reported low-intensity work stress. A history of depression was found in 30%. Progression-free survival at 6 months was 45.3% and median overall survival was estimated to be 16.5 months. Level and presence of stress did not differ based on location of tumour. No association was found between stress and tumour progression or overall survival.Conclusion: A majority of patients in this study had low exposure to stressors as well as low stress level. Psychological stress did not seem to favour the emergence of glioblastoma or survival.

Absence of Mycoplasma spp. in nightingales (Luscinia megarhynchos) and blue (Cyanistes caeruleus) and great tits (Parus major) in Germany and its potential implication for evolutionary studies in birds

Mycoplasma spp. are important pathogens in poultry and cause high economic losses for poultry industry worldwide. In other bird species (e.g. white storks, birds of prey, and several waterfowl species), Mycoplasma spp. are regularly found in healthy individuals, hence, considered apathogenic or part of the microbiota of the upper respiratory tract. However, as Mycoplasma spp. are absent in healthy individuals of some wild bird species, they might play a role as respiratory pathogen in these bird species, e.g. Mycoplasma gallisepticum in house finches. The knowledge on the occurrence of Mycoplasma spp. in wild birds is limited. To evaluate the relevance of Mycoplasma spp. in free-ranging nightingales and tits, 172 wild caught birds were screened for the presence of mycoplasmas. The birds were sampled via choanal swabs and examined via molecular methods (n = 172) and, when possible, via culture (n = 142). The Mycoplasma sp. was determined by sequencing the 16S rRNA gene and 16S-23S Intergenic Transcribed Spacer Region. All birds were tested negative for mycoplasmas via PCR and/or mycoplasmal culture. Hence, free-ranging nightingales and tits do not show any mycoplasma in their microbial flora of the respiratory tract. Therefore, these songbird species may suffer from clinical mycoplasmosis when being infected. We hypothesize that birds relying on their vocal ability for reproduction have excluded mycoplasmas from their respiratory flora compared to other bird species.