Aberrant brain network connectivity in presymptomatic and manifest Huntington's disease: A systematic review

Resting‐state functional magnetic resonance imaging (rs‐fMRI) has the potential to shed light on the pathophysiological mechanisms of Huntington's disease (HD), paving the way to new therapeutic interventions. A systematic literature review was conducted in three online databases according to PRISMA guidelines, using keywords for HD, functional connectivity, and rs‐fMRI. We included studies investigating connectivity in presymptomatic (pre‐HD) and manifest HD gene carriers compared to healthy controls, implementing seed‐based connectivity, independent component analysis, regional property, and graph analysis approaches. Visual network showed reduced connectivity in manifest HD, while network/areas underpinning motor functions were consistently altered in both manifest HD and pre‐HD, showing disease stage‐dependent changes. Cognitive networks underlying executive and attentional functions showed divergent anterior–posterior alterations, possibly reflecting compensatory mechanisms. The involvement of these networks in pre‐HD is still unclear. In conclusion, aberrant connectivity of the sensory‐motor network is observed in the early stage of HD while, as pathology spreads, other networks might be affected, such as the visual and executive/attentional networks. Moreover, sensory‐motor and executive networks exhibit hyper‐ and hypo‐connectivity patterns following different spatiotemporal trajectories. These findings could potentially help to implement future huntingtin‐lowering interventions.     

Cross-talks in colon cancer between RAGE/AGEs axis and inflammation/immunotherapy

The tumour microenvironment is the result of the activity of many types of cells in various metabolic states, whose metabolites are shared between cells. This cellular complexity results in an availability profile of nutrients and reactive metabolites such as advanced glycation end products (AGE). The tumour microenvironment is not favourable to immune cells due to hypoxia and for the existence of significant competition between various types of cells for a limited nutrient pool. However, it is now known that cancer cells can influence the host''s immune reaction through the expression and secretion of numerous molecules. The microenvironment can therefore present itself in different patterns that contribute to shaping immune surveillance. Colorectal cancer (CRC) is one of the most important causes of death in cancer patients. Recently, immunotherapy has begun to give encouraging results in some groups of patients suffering from this neoplasm. The analysis of literature data shows that the RAGE (Receptor for advanced glycation end products) and its numerous ligands contribute to connect the energy metabolic pathway, which appears prevalently disconnected by mitochondrial running, with the immune reaction, conditioned by local microbiota and influencing tumour growth. Understanding how metabolism in cancer and immune cells shapes response and resistance to therapy, will provide novel potential strategies to increase both the number of tumour types treated by immunotherapy and the rate of immunotherapy response. The analysis of literature data shows that an immunotherapy approach based on the knowledge of RAGE and its ligands is not only possible, but also desirable in the treatment of CRC.     

Acid base disorders in patients with COVID-19

Purpose

Acid–base derangement has been poorly described in patients with coronavirus disease 2019 (COVID-19). Considering the high prevalence of pneumonia and kidneys injury in COVID-19, frequent acid–base alterations are expected in patients admitted with SARS-Cov-2 infection. The study aimed to assess the prevalence of acid–base disorders in symptomatic patients with a diagnosis of COVID-19.

Methods

The retrospective study enrolled COVID-19 patients hospitalized at the University Hospital of Modena from 4 March to 20 June 2020. Baseline arterial blood gas (ABG) analysis was collected in 211 patients. In subjects with multiple ABG analysis, we selected only the first measurement. A pH of less than 7.37 was categorized as acidemia and a pH of more than 7.43 was categorized as alkalemia.

Results

ABG analyses revealed a low arterial partial pressure of oxygen (PO₂, 70.2?±?25.1 mmHg), oxygen saturation (SO₂, 92%) and a mild reduction of PO₂/FiO₂ ratio (231?±?129). Acid–base alterations were found in 79.7% of the patient. Metabolic alkalosis (33.6%) was the main alteration followed by respiratory alkalosis (30.3%), combined alkalosis (9.4%), respiratory acidosis (3.3%), metabolic acidosis (2.8%) and other compensated acid–base disturbances (3.6%). All six patients with metabolic acidosis died at the end of the follow-up.

Conclusion

Variations of pH occurred in the majority (79.7%) of patients admitted with COVID-19. The patients experienced all the type of acid–base disorders, notably metabolic and respiratory alkalosis were the most common alterations in this group of patients.

     

Neural underpinnings of the ‘agent brain’: new evidence from transcranial direct current stimulation

Intentional binding (IB) refers to the temporal compression between a voluntary action and its sensory effect, and it is considered an implicit measure of sense of agency (SoA), that is, the capacity to control one's own actions. IB has been thoroughly studied from a behavioural point of view but only few studies have investigated its neural underpinnings, always using the same two paradigms. Although providing evidence that the supplementary motor complex is involved, findings are still too scarce to draw definitive conclusions. The aim of the present study was to establish a causal relationship between the pre‐supplementary motor area (pre‐SMA), known for its key role in action planning and initiation, and IB by means of transcranial direct current stimulation (tDCS). Participants underwent anodal, cathodal and sham control stimulations during three separate sessions (Experiment I). Subsequently, they underwent the same stimulation protocol (Experiment II) using as control a region potentially involved in the processing of the sensory effects of voluntary action (i.e., the right primary auditory cortex for the auditory effects of action). A significant reduction in IB was found only after stimulation of the pre‐SMA, which supports the causal contribution of this prefrontal area in the perceived linkage between action and its effects. As SoA could be disrupted in many psychiatric and neurological diseases, these results have direct clinical relevance as tDCS could be successfully used in this domain in virtue of the promising advantages it offers for rehabilitation.     

Qualitative mucin disorders in patients with primary Sjögren's syndrome: a literature review

Background It is a common opinion that Primary Sjögren Syndrome (pSS) damages the exocrine glands and determines the reduction of secreted saliva, some studies show that there are qualitative anomalies of the mucins produced in saliva, including MUC7, MUC5B, MUC1. The purpose of this study is to trace all the information useful to establish whether there is a qualitative or quantitative defect of the mucins in the pSS. Material and Methods We reviewed the literature by looking for publications relevant to the topic in electronic databases. Sixteen articles met the search criteria. The studies were divided into two categories, those that studied the rheological characteristics of the saliva and those that studied the structural and / or metabolism modifications of the muciparous cells in the salivary glands. Results in Patients with pSS, xerostomia and the reduction of salivary spinnbarkeit are only partially related to the reduction of the unstimulated salivary flow. In pSS, pathological alterations of mucins’ chemical-physical properties prevail as a cause of the clinical characteristics. Moreover, in pSS there are structural and metabolism changes in salivary glands’ muciparous cells. Conclusions There is much evidence that supports the presence of qualitative alterations in the saliva’s rheological properties in Patients with pSS, and these are the main cause, more than the reduction of the unstimulated salivary flow, of the disease clinical characteristics - dry mouth and complications in the oral cavity. Therefore we propose to add to the classification criteria of pSS also a qualitative test of salivary glycoproteins. Key words:Primary Sjögren''s syndrome, mucin, MUC7, MUC5B, MUC1, sulphate oligosaccharides.     

Pituitary tumor apoplexy presenting as infective meningoencephalitis

We report on a case of a 80-year-old man who developed progressive drowsiness with headache, fever and signs of meningeal irritation 2 days after a head trauma. Suspecting an infective meningoencephalitis, the patient was treated with wide spectrum antibiotic and antiviral therapy. Brain CT scan revealed a previously unknown pituitary expansive lesion. A brain MRI study confirmed the presence of an intrasellar lesion, which presented remarkable contrast ring enhancement, and showed non-specific inflammatory tissue on the clivus, possibly responsible of the clinical features of sterile meningitis. A biopsy proven diagnosis of pituitary apoplexy was made. This case highlights MRI as an important investigation for earlier recognition of pituitary apoplexy that can present with a clinical picture resembling an infective meningoencephalitis.     

Posttraumatic dystonia and hemiplegic migraine: different expressions of neuronal hyperexcitability?

The development of focal hand dystonia after a traumatic injury of the central or the peripheral nervous system is a rare condition with multifactorial predisposing factors. We report on a patient who developed focal dystonia of the left hand after a cervical whiplash injury. Magnetic resonance imaging did not show cerebral or spinal lesions, whereas a brain F-FDG PET scan revealed hypometabolism of the right primary sensory-motor cortex extending to the inferior and superior parietal lobule. The patient had a history of recurrent migraine attacks. Four months before the whiplash injury, she had transient dystonic posture of the left hand during a hemiplegic migraine attack. Brain magnetic resonance imaging scan and neurovascular investigations were negative. Among the predisposing factors to the development of trauma-induced dystonia, a putative role of neuronal hyperexcitability, shared by migraine and dystonia, is discussed.