COVID-19 Beyond the Lungs

Since December 2019, the world has been shaken by the spread of a highly pathogen virus, causing severe acute respiratory syndrome (SARS-Cov2), which emerged in Wuhan, China. SARS-Cov2 is known to cause acute pneumonia: the cardinal feature of coronavirus disease 2019 (COVID-19). Clinical features of the disease include respiratory distress, loss of spontaneous breathing, and sometimes neurologic signs such as headache and nausea and anosmia, leading to suppose a possible involvement of the nervous system as a potential target of SARS-CoV2. The chapter will shed light on the recent clinical and experimental data sustaining the involvement of the nervous system in the pathophysiology of COVID-19, based on several case reports and experimental data reporting the possible transmission of SARS-CoV2 throughout the peripheral nerves to the brain cardiorespiratory centers. Thus, understanding the role of the nervous system in the course of clinical symptoms of COVID-19 is important in determining the appropriate therapeutic approach to combat the disease.

Hypodopaminergic state of the nigrostriatal pathway drives compulsive alcohol use

The neurobiological mechanisms underlying compulsive alcohol use, a cardinal feature of alcohol use disorder, remain elusive even though they have often been suggested to involve dopamine (DA). Here, we found that rats expressing compulsive alcohol-related behavior, operationalized as punishment-resistant self-administration, showed a decrease in DA levels restricted to the dorsolateral territories of the striatum, the main output structure of the nigrostriatal DA pathway. We then causally demonstrated that a chemogenetic-induced selective hypodopaminergia of this pathway results in compulsive alcohol self-administration in rats otherwise resilient, accompanied by the emergence of alcohol withdrawal-like motivational impairments. These results demonstrate a major implication of tonic nigrostriatal hypodopaminergic state in alcohol addiction and provide new insights into our understanding of the neurobiological mechanisms underlying compulsive alcohol use.

Lipid hydroperoxides promote muscle atrophy through lysosomal amplification

Reactive oxygen species (ROS) is a cardinal feature of skeletal muscle atrophy. However, ROS refers to a collection of radical molecules whose cellular signals are vast, and it is unclear which downstream consequences of ROS are responsible for the loss of muscle mass and strength.1,2 Here we show that lipid hydroperoxides (LOOH) are increased with age and disuse, and the accumulation of LOOH by suppression of glutathione peroxidase 4 (GPx4) is sufficient to augment muscle atrophy. Strikingly, genetic and pharmacologic suppression of muscle LOOH robustly prevented the reduction of both muscle mass and force-generating capacity. LOOH promoted atrophy in a lysosomal-dependent, proteasomal-independent manner, and the suppression of autophagic machinery was sufficient to prevent muscle atrophy and weakness. Indeed, the lysosome is essential for the amplification of LOOH induced by oxidative stress. Our findings provide novel insights for the role of LOOH in muscle atrophy including a therapeutic implication by pharmacologic suppression.

Cyclopia - A Rare Lethal Malformation

Cyclopia is the rare manifestation of most severe degree of alobar holoprosencephaly1. Its most cardinal feature is presence of single eye or partially divided eye in a single socket at mid face with varying degrees of fusion of globes. The teratogenic factors leading to this anomaly include genetics, drugs, infection, radiation. Very few reports have documented this anomaly in newborn. Hence we present a case of stillborn baby of cyclopia with synophthalmia to a 27 year old woman who presented in second stage of labour with USG showing placenta previa. Early prenatal diagnosis, genetic study and proper management of this anomaly should be emphasized for better outcome in future. Key words: cyclopia; holoprosencephaly; teratogenic; synophthalmia; prenatal diagnosis.

AN OPEN-LABEL CLINICAL TRIAL TO PROVE THE EFFICACY OF HIRUDOTHERAPY IN REDUCING THE INCREASED INTRA-OCULAR PRESSURE IN GLAUCOMA

Glaucoma is a chronic disease condition prevalent globally leading to blindness. It results in optic neuropathy which is very difficult to manage. An increase in intraocular pressure is a cardinal feature in most cases. This study aims at lowering the intraocular pressure by leech therapy, which is a conventional treatment method described in Ayur- veda. Leech therapy was conducted in the selected patients and intraocular pressure before and after treatment were recorded. The study showed clinically and statistically significant changes in the intraocular pressure. Keywords: Leech therapy, glaucoma, intraocular pressure

Back to basics: a rare and aggressive case of Aggregatibacter aphrophilus endocarditis

ABSTRACT We present the case of a 25-year-old with a history of bicuspid aortic valve and ascending aortopathy who was successfully treated for infective endocarditis (IE) due to Aggregatibacter aphrophilus. His clinical course was complicated by a large aortic root abscess not initially visualised on transthoracic echocardiography or computerised tomography. The cardinal feature of progressive prolongation of the PR interval on serial electrocardiograms was the only sign associated with clinical deterioration and was the trigger for rapid investigation and urgent management. Our case emphasises the importance of simple bedside tests to identify dynamic clinical scenarios and the requirement for early further imaging in the management of IE.

A Systematic Review of the Inclusion of Non-Inflammatory Ultrasonographic Enthesopathy Findings in Enthesitis Scoring Indices

Ultrasound has advanced the diagnosis and management of patients with inflammatory rheumatic conditions. It can be used to identify and monitor enthesitis, a cardinal feature of spondyloarthropthies. Several enthesitis scoring systems utilizing ultrasound to determine entheseal involvement have been developed. These scoring systems generally rely on determining the presence or absence of erosions, tendon enlargement, power Doppler signal, or enthesophytes. This systematic review identified ultrasound scoring systems that have been utilized for evaluating enthesitis and what key components derive the score. Review of these scoring systems, however, demonstrated confounding as some of the score components including enthesophytes may be seen in non-inflammatory conditions and some components including erosions can be seen from chronic damage, but not necessarily indicate active inflammatory disease. What is furthermore limiting is that currently there is not an agreed upon term to describe non-inflammatory enthesopathies, further complicating these scoring systems. This review highlights the need for a more comprehensive ultrasound enthesopathy scoring index.

Hippocampal Volume and Amyloid PET Status Three Years After Ischemic Stroke: A Pilot Study

Hippocampal atrophy is seen in many neurodegenerative disorders and may be a cardinal feature of vascular neurodegeneration. We examined hippocampal volume (HV) in a group of ischemic stroke survivors with amyloid 18F-NAV4694 PET imaging three years after stroke. We compared HV between the amyloid-positive (n = 4) and amyloid-negative (n = 29) groups, and associations with co-morbidities using Charlson Comorbidity Indices and multi-way ANOVA. Amyloid status was not associated with verbal or visual delayed free recall memory indices or cognitive impairment. We found no association between amyloid status and HV in this group of ischemic stroke survivors.

(Re)contextualizing the Trauma to Prevent or Treat PTSD-Related Hypermnesia

A cardinal feature of Post-traumatic stress-related disorder (PTSD) is a paradoxical memory alteration including both intrusive emotional hypermnesia and declarative/contextual amnesia. Most preclinical, but also numerous clinical, studies focus almost exclusively on the emotional hypermnesia aiming at suppressing this recurrent and highly debilitating symptom either by reducing fear and anxiety or with the ethically questionable idea of a rather radical erasure of traumatic memory. Of very mixed efficacy, often associated with a resurgence of symptoms after a while, these approaches focus on PTSD-related symptom while neglecting the potential cause of this symptom: traumatic amnesia. Two of our preclinical studies have recently demonstrated that treating contextual amnesia durably prevents, and even treats, PTSD-related hypermnesia. Specifically, promoting the contextual memory of the trauma, either by a cognitivo-behavioral, optogenetic or pharmacological approach enhancing a hippocampus-dependent memory processing of the trauma normalizes the fear memory by inducing a long-lasting suppression of the erratic traumatic hypermnesia.