Chronic long-COVID syndrome: A protracted COVID-19 illness with neurological dysfunctions

After almost a year of COVID-19, the chronic long-COVID syndrome has been recognized as an entity in 2021. The patients with the long-COVID are presenting with ominous neurological deficits that with time are becoming persistent and are causing disabilities in the affected individuals. The mechanisms underlying the neurological syndrome in long-COVID have remained obscure and need to be actively researched to find a resolution for the patients with long-COVID. Here, the factors like site of viral load, the differential immune response, neurodegenerative changes, and inflammation as possible causative factors are debated to understand and investigate the pathogenesis of neuro-COVID in long-COVID syndrome

Cloned Microglias with Novel Delivery System in Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic inflammatory neurological disease of the Central Nervous System (CNS), characterized by demyelination and activation of microglia. Mitochondrial mutations and dysfunctions in microglial cells are thought to contribute to the detrimental effects of neuroinflammation seen in MS. The Somatic Nuclear Transfer (SCNT) technology offers a more practical mode of therapy in MS, this method would attempt to dilute and/or progressively replace the mutated and activated microglia with cloned Olfactory Ensheathing Cells (OEC) with remyelinating and scavenging properties which would attempt to limit the progression of MS. Applying SCNTderived Embryonic Stem (ES) cells based therapy by cloning Olfactory Ensheathing Cells (OEC), engineered with an autologous nuclear component of the recipient OEC with a healthy donor oocyte. The inner cell mass of the subsequently developed blastocyst would be the source to generate the radial microglia to be used for cell therapy in MS. The novel proposed transcribrial route device offers a painless mode of cell transplantation to the brain. This mode of generating cloned glia and its transplantation to the brain is expected to replace the mutated and activated microglia of the patients with MS and use the regenerative and remyelinating and scavenging properties of the OEC’s, as has been seen in clinical trials in patients with spinal cord injuries. The use of SCNT to develop isogenic ES cellbased therapies for the prevention and treatment of MS associated with mtDNA mutations may open a new avenue of designer’s targeted cell therapy unique for the patients with MS. The proposed “transcribrial device” to access the brain can be an advantageous route of delivery of cloned cells to the brain

Covid-19 infection; loss of taste, smell, and neurogenic respiratory failure

Neurological Signs and Symptoms in COVID-19: Like the rest of the world, Pakistan is been gripped by unprecedented and complex burden of COVID-19. While the diseases got upgraded to a pandemic, the preparedness of even the first world countries to combat COVID-19 is distressing, as there seems to be a lack of clear strategy to tackle the disease spread and treatment

Neurological manifestations of COVID-19

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has turned out to be a formidable pandemic. Upcoming evidence from confirmed cases of COVID-19 suggests an anticipated incursion of patients with neurological manifestations in the weeks to come. An expression of the angiotensin-converting enzyme 2 (ACE 2), the cellular receptor for SARS-CoV-2 over the glial cells and neurons have made the brain a potential target. Neurotoxicity may occur as a result of direct, indirect and post-infectious complications. Attention to neurological deficits in COVID-19 is fundamental to ensure appropriate, timely, beneficial management of the affected patients. Most common neurological manifestations seen include dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizures. Anosmia and ageusia have recently been hinted as significant early symptoms in COVID-19. As cases with neurological deficits in COVID-19 emerge, the overall prognosis is yet unknown

In vitro efficacy of clinically available drugs against growth and viability of Acanthamoeba castellanii keratitis isolate belonging to the T4 genotype

The effects of clinically available drugs targeting muscarinic cholinergic, adrenergic, dopaminergic, and serotonergic receptors; intracellular calcium levels and/or the function of calcium-dependent biochemical pathways; ion channels; and cellular pumps were tested against a keratitis isolate of Acanthamoeba castellanii belonging to the T4 genotype. In vitro growth inhibition (amoebistatic) assays were performed by incubating A. castellanii with various concentrations of drugs in the growth medium for 48 h at 30°C. To determine amoebicidal effects, amoebae were incubated with drugs in phosphate-buffered saline for 24 h, and viability was determined using trypan blue exclusion staining. For controls, amoebae were incubated with the solvent alone. Of the eight drugs tested, amlodipine, prochlorperazine, and loperamide showed potent amoebicidal effects, as no viable trophozoites were observed (\u3e95% kill rate), while amiodarone, procyclidine, digoxin, and apomorphine exhibited up to 50% amoebicidal effects. In contrast, haloperidol did not affect viability, but all the drugs tested inhibited A. castellanii growth. Importantly, amlodipine, prochlorperazine, and loperamide showed compelling cysticidal effects. The cysticidal effects were irreversible, as cysts treated with the aforementioned drugs did not reemerge as viable amoebae upon inoculation in the growth medium. Except for apomorphine and haloperidol, all the tested drugs blocked trophozoite differentiation into cysts in encystation assays. Given the limited availability of effective drugs to treat amoebal infections, the clinically available drugs tested in this study represent potential agents for managing keratitis and granulomatous amoebic encephalitis caused by Acanthamoeba spp. and possibly against other meningoencephalitis-causing amoebae, such as Balamuthia mandrillaris and Naegleria fowleri

Can clinical staging of primary amoebic meningoencephalitis be of any therapeutic benefit

Naegleria fowleri, is a free-living amoeba (FLA) known to infect humans and cause a fatal disease called primary amoebic meningoencephalitis (PAM). All of the patients are commonly admitted to the emergency room (ER). Often, treatment in the ER is delayed due to the rarity of disease leading to a delay in the diagnosis and late arrival of patients to the ER. The attempts to reduce raised intracranial pressure and subsequent herniation of the brain stem are challenging and become the cause of death in the affected patients during their stay in ER. Use of drugs like mannitol to reduce raised intra-cerebral pressure (ICP) could prove dangerous in the presence of cerebral haemorrhage and this fact could be overlooked during the management of patients with PAM. No precise therapy is followed for PAM, and most often a course of broad spectrum anti-protozoal drugs is employed. A CDC recommended drug miltefosine has show success in early diagnosed cases. So far, there is no clinical staging of PAM, and patients are managed for the complications that develop while their stay in the ER. Given the health scare associated with N. fowleri in countries with tropical climates, and its potential ability to cause severe meningoencephalitis that often progresses to lethal outcomes, we believe it is imperative to stage PAM into clear progressive stages to help its management in the ER and debate its therapeutic gains. Such a clinical staging could aid in efforts to diagnose and treat PAM. Furthermore, it will help in raising public awareness, in educating healthcare and allied personne

Evidence of the COVID-19 virus targeting the CNS: Tissue distribution, host-virus interaction, and proposed neurotropic mechanisms

The recent outbreak of coronavirus infectious disease 2019 (COVID-19) has gripped the world with apprehension and has evoked a scare of epic proportion regarding its potential to spread and infect humans worldwide. As we are in the midst of an ongoing pandemic of COVID-19, scientists are struggling to understand how it resembles and differs from the severe acute respiratory syndrome coronavirus (SARS-CoV) at the genomic and transcriptomic level. In a short time following the outbreak, it has been shown that, similar to SARS-CoV, COVID-19 virus exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells. This finding raises the curiosity of investigating the expression of ACE2 in neurological tissue and determining the possible contribution of neurological tissue damage to the morbidity and mortality caused by COIVD-19. Here, we investigate the density of the expression levels of ACE2 in the CNS, the host-virus interaction and relate it to the pathogenesis and complications seen in the recent cases resulting from the COVID-19 outbreak. Also, we debate the need for a model for staging COVID-19 based on neurological tissue involvement

Recommendations for the management of Acanthamoeba keratitis

The aim of this letter is to provide the scientific basis of the successful prognosis observed in Acanthamoeba keratitis patients in the absence of anti-Acanthamoeba agents. Patients were treated for photophobia with anticholinergics (Atropine), and for inflammation and pain, they were given topical Diclofenac sodium. The patients responded well with the aforementioned combination. It was suggested that the successful prognosis was due to suppression of the inflammation. Here, we explained that anticholinergic agent showed potent anti-amoebic effects. Thus the successful prognosis observed in AK cases were not merely due to regulation of the inflammatory process, but were most likely due to amoebicidal effects of anticholinergic agent

Innovations in surgery between the past and future: A narrative review of targeted literature

Innovation is the introduction of a new method or technology designed to change the way things are done. History is full of remarkable innovations in surgery over the years as surgeons have always been innovating and pioneering latest techniques and equipment that can benefit the mankind. Though persistent, progress has been far from uniform. Despite all the bells and whistles that these innovations bring to the table, the little acknowledged fact is that they are only accessible to a very small proportion of the global population. Five billion people on this planet do not even have access to an operating room when needed. It has been reported that conditions requiring surgery are responsible for one-third of all the deaths in the world. The current narrative review was planned to focus on the importance of innovations in surgery, to highlight the problems that were faced by resource-restricted countries in the past, and the necessity of innovative solutions to improve global surgical care in the future