The neuronal regulation of metabolic and behavioral responses to different diets and feeding regimens is an important research area. Herein, we investigated if the opioid peptide dynorphin modulates feeding behavior and metabolism. Mice lacking dynorphin peptides (KO) were exposed to either a normal diet (ND) or a high-fat diet (HFD) for a period of 12 weeks. Additionally, mice had either time-restricted (TR) or ad libitum (AL) access to food. Body weight, food intake and blood glucose levels were monitored throughout the 12-week feeding schedule. Brain samples were analyzed by immunohistochemistry to detect changes in the expression levels of hypothalamic peptides. As expected, animals on HFD or having AL access to food gained more weight than mice on ND or having TR access. Unexpectedly, KO females on TR HFD as well as KO males on AL ND or AL HFD demonstrated a significantly increased body weight gain compared to the respective WT groups. The calorie intake differed only marginally between the genotypes: a significant difference was present in the female ND AL group, where dynorphin KO mice ate more than WT mice. Although female KO mice on a TR feeding regimen consumed a similar amount of food as WT controls, they displayed significantly higher levels of blood glucose. We observed significantly reduced levels of hypothalamic orexigenic peptides neuropeptide Y (NPY) and orexin-A in KO mice. This decrease became particularly pronounced in the HFD groups and under AL condition. The kappa opiod receptor (KOR) levels were higher after HFD compared to ND feeding in the ventral pallidum of WT mice. We hypothesize that HFD enhances dynorphin signaling in this hedonic center to maintain energy homeostasis, therefore KO mice have a more pronounced phenotype in the HFD condition due to the lack of it. Our data suggest that dynorphin modulates metabolic changes associated with TR feeding regimen and HFD consumption. We conclude that the lack of dynorphin causes uncoupling between energy intake and body weight gain in mice; KO mice maintained on HFD become overweight despite their normal food intake. Thus, using kappa opioid receptor agonists against obesity could be considered as a potential treatment strategy.

No abstract

Covid-19 is a disease caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). SARS-CoV-2 which affects respiratory, gastrointestinal and neurological systems. It not only causes atypical pneumonia with acute respiratory distress syndrome (ARDS), but also, acute cardiac damage, acute renal failure and gastrointestinal complications.1 It is a disorder that not only presents with fever and respiratory symptoms but can involve the nervous system with varied presentations in form of cerebrovascular accident, loss of taste, loss of smell, myelopathy, neuropathy, meningitis and encephalitis.2 Some cases of Guillain–Barre syndrome (GBS) associated with SARS-CoV-2 have been reported in the literature. GBS is acute immune mediated inflammatory polyradiculopathy.3 GBS presents as limb weakness or cranial nerve weakness, loss of deep tendon reflex, autonomic dysfunction due to peripheral nerve demyelination and sensory root demyelination.

In this case report we discuss a patient with neurological manifestations thought to be a case of hepatic encephalopathy. With no improvement in symptoms despite treatment, it created a diagnostic dilemma. Eventually, toxicological investigations were done which revealed that heavy metal poisoning could be the possible culprit. Encephalopathy is characterised by impaired mental state as a result of a diffuse brain dysfunction or other psychiatric condition that induces unconsciousness, typically followed by diffuse electroencephalogram (EEG) anomalies. Both primary neurological and systemic disorders are root causes of encephalopathy. Encephalopathy results from several causes such as liver failure or liver cancer, metabolic abnormalities, anoxic encephalopathy, infections, exposure to harmful compounds such as lithium paint, synthetic contaminants (toxins), inflammations (systemic lupus erythematous, sarcoidosis), drug induced, demyelination (e.g., multiple sclerosis), degenerative process like Alzheimer disease, Parkinson disease and hereditary encephalopathies such as leukodystrophy of the white matter. 1 Humans have used heavy metals since many years. While many harmful health effects of heavy metals have long been established, exposure to heavy metals continues to rise in some parts of the world, especially in underdeveloped countries. Emissions have decreased over the past 100 years in most developed countries. Heavy metals are prevalent and remain in the ecosystem, in general causing bio amplification. Living systems frequently associate with heavy metals in different proportions in the habitat. Heavy metal exposure induces lipid peroxidation, Deoxyribonucleic Acid (DNA) damage and protein modification by generation of oxygen free radicals. Exposure to these metals occurs in occupational areas by equipment, air, food and drinking water. Prolonged exposure to heavy metals may lead to neurotoxicity and brain damage. When symptoms of toxic encephalopathy emerge immediately following single acute exposure to high levels of toxic chemicals it is termed as acute toxic encephalopathy. Other than that if symptoms emerge insidiously over time in association with repeated or chronic exposure to low levels of neurotoxins it is called as chronic toxic encephalopathy. 2 In some cases, diagnosis of toxic encephalopathy is complicated by the fact that toxic chemicals can also damage liver and kidneys. In these cases hepatic dysfunction must be successfully treated before diagnosis of toxic encephalopathy can be considered. It is a diagnosis of exclusion, so a full work up for other possible aetiologies such as hepatic, uremic and infectious should be done. In this case report we have discussed heavy metal encephalopathy masquerading as hepatic dysfunction.

Libman-Sacks endocarditis is non-infectious thrombotic involvement of cardiac valves seen in systemic lupus erythematosus.1,2 Mitral valve followed by aortic valve are involved in systemic lupus erythematosus. However, involvement of tricuspid valve is rare.3 A case of a 36-year-old woman with systemic lupus erythematosus with isolated tricuspid valve endocarditis has been reported here. Within the background of the relevant medical literature, this is a rare event. In systemic lupus erythematosus (SLE) patients, mostly the aortic and mitral valves are affected.4 Echo shows evidence of vegetation in tip and septa of tricuspid valve which is suggestive of Libman-Sacks endocarditis. In our case we have discussed Libman-Sacks endocarditis involving tricuspid valve.