Prospects and Challenges in Developing mRNA Vaccines for Infectious Diseases and Oncogenic Viruses.

mRNA vaccines have emerged as an optimistic technological platform for vaccine innovation in this new scientific era. mRNA vaccines have dramatically altered the domain of vaccinology by offering a versatile and rapid approach to combating infectious diseases and virus-induced cancers. Clinical trials have demonstrated efficacy rates of 94-95% in preventing COVID-19, and mRNA vaccines have been increasingly recognized as a powerful vaccine platform. Although mRNA vaccines have played an essential role in the COVID-19 pandemic, they still have several limitations; their instability and degradation affect their storage, delivery, and over-all efficiency. mRNA is typically enclosed in a transport mechanism to facilitate its entry into the target cell because it is an unstable and negatively charged molecule. For instance, mRNA that is given using lipid-nanoparticle-based vaccine delivery systems (LNPs) solely enters cells through endocytosis, establishing an endosome without damaging the cell membrane. The COVID-19 pandemic has accelerated the development of mRNA vaccine platforms used to treat and prevent several infectious diseases. This technology has the potential to change the future course of the disease by providing a safe and effective way to combat infectious diseases and cancer. A single-stranded genetic sequence found in mRNA vaccines instructs host cells to produce proteins inside ribosomes to elicit immunological responses and prepare the immune system to fight infections or cancer cells. The potential applications of mRNA vaccine technology are vast and can lead to the development of a preferred vaccine pattern. As a result, a new generation of vaccinations has gradually gained popularity and access to the general population. To adapt the design of an antigen, and even combine sequences from different variations in response to new changes in the viral genome, mRNA vaccines may be used. Current mRNA vaccines provide adequate safety and protection, but the duration of that protection can only be determined if further clinical research is conducted.

Bromocriptine: does this drug of Parkinson's disease have a role in managing cardiovascular diseases?

Cardiovascular disease (CVD) is the most common cause of morbidity and mortality worldwide. Bromocriptine is a partial antagonist for D1 dopamine receptors while also serving as a selective agonist on D2 dopamine receptors as a dopamine receptor agonist. Apart from prolactin inhibiting action, bromocriptine has some beneficial effects on the blood pressure, plasma norepinephrine levels and vascular resistance. Dopamine D2 receptor activation of bromocriptine is associated with the antihypertensive effect, which lowers blood pressure via inhibiting sympathetic nerve activity and Na/K ATPase activity. Plasma levels of the pro-inflammatory cytokines such as interleukin (IL)-1B and IL-18, chemokine CCL2/ MCP-1/, and the pro-inflammatory hormone prolactin, all of which are elevated and linked to accelerated cardiometabolic illness, were decreased because of bromocriptine therapy. The most common side effects of Bromocriptine use are dizziness, nausea, headache, vomiting and hypotension. Bromocriptine is mainly contraindicated in patients with syncope with hypotension, psychosis, and type I diabetes mellitus. The authors suggest that developing therapies directed to increase D2 receptor expression and function by drugs like Bromocriptine can provide practical and novelistic approaches to prevent and manage myocardial and renal injury in the cardiovascular disease patients.

Mechanical thrombectomy for AIS from large vessel occlusion - current trends and future perspectives.

Stroke is found to be one of the global top causes of mortality and the major factor in years of life with a handicap (DALYs). Ischemic strokes contributed to nearly 70% of all strokes worldwide. For endovascular thrombectomy in acute ischemic stroke with large vessel obstruction (AIS-LVO), using stent retrievers and/or reperfusion catheters has become the gold standard of therapy. The methodology involved keyword-based search in databases like PubMed, Embase, and Google Scholar for recent publications on mechanical thrombectomy (MT), AIS, large vessel occlusion (Large Vessel Occlusion (LVO)), screening relevant articles, retrieving full texts, and synthesizing key findings on procedural advancements, patient selection, COVID-19 (coronavirus disease 2019) impact, delay effects, effectiveness, clinical outcomes, and future perspectives. Only people with substantial cerebral artery obstruction may do well from MT. This includes the distal carotid artery and the proximal middle cerebral artery (segment M1). The size of a blocked vessel and NIHSS (National Institute of Health Stroke Scale) score are directly connected. Both the 2018 and 2019 versions of the AHA/ASA (American Heart Association/American Stroke Association) Guidelines for the Early Management of Patients with Acute Ischemic Stroke contained the recommendations that cases with AIS-LVO get endovascular therapy when administered during the time frame of 0-6 h after onset (Grade IA evidence). It is questionable whether this group of patients can be managed without the need for intravenous tissue plasminogen activator at the onset. When functional independence [modified Rankin Scale (mRS) score 2] was present at long-term follow-up, the endovascular intervention was favored. Tenecteplase, which differs from alteplase in terms of genetic variation, has a greater half-life and a higher level of fibrin selectivity, enabling bolus infusion. Studies have also demonstrated its efficacy and safety, as well as its long-term cost-effectiveness.

The neglected continuously emerging Marburg virus disease in Africa: A global public health threat.

Background and Aim: Severe viral hemorrhagic fever (VHF) is caused by Marburg virus which is a member of the Filoviridae (filovirus) family. Many Marburg virus disease (MVD) outbreaks are reported in five decades. A major notable outbreak with substantial reported cases of infections and deaths was in 2022 in Uganda. The World Health Organisation (WHO) reported MVD outbreak in Ghana in July 2022 following the detection of two probable VHF patients there. Further, the virus was reported from two other African countries, the Equatorial Guinea (February 2023) and Tanzania (March 2023). There have been 35 deaths out of 40 reported cases in Equatorial Guinea, and six of the nine confirmed cases in Tanzania so far. Methods: Data particularly on the several MVD outbreaks as reported from the African countries were searched on various databases including the Pubmed, Scopus, and Web-of-science. Also, the primary data and reports from health agencies like the WHO and the Centers for Disease Control and Prevention CDC) were evaluated and the efficacy reviewed. Results: Chiroptera in general and bat species like Rousettus aegyptiacus and Hipposideros caffer in particular are natural reservoirs of the Marburg virus. MVD-infected nonhuman primate African fruit-bat and the MVD-infected humans pose significant risk in human infections. Cross-border viral transmission and its potential further international ramification concerns raise the risk of its rapid spread and a potential outbreak. Occurrence of MVD is becoming more frequent in Africa with higher case fatality rates. Effective prophylactic and therapeutic interventions to counter this deadly virus are suggested. Conclusion: In the face of the lack of effective therapeutics and preventives against MVD, supportive care is the only available option which contributes to the growing concern and disease severity. In view of the preventive approaches involving effective surveillance and monitoring system following the "One Health" model is extremely beneficial to ensure a healthy world for all, this article aims at emphasizing several MVD outbreaks, epidemiology, zoonosis of the virus, current treatment strategies, risk assessments, and the mitigation strategies against MVD.

A case of tension pneumoperitoneum with fecal peritonitis due to high-pressure air insufflation through the anus.

Key Clinical Message: The reckless or ridiculous usage of high pressure compressed air could lead to disastrous consequences as demonstrated in this case. Injuries from a barotrauma can vary from a simple mucosal laceration to tension pneumoperitoneum causing abdominal compartment syndrome. Decompression by a wide-bore needle can be done as depicted in our patient to provide immediate relief. Abstract: Rectal perforation most commonly occurs due to trauma, but rarely due to a high pressure compressed air passing through the anus as a part of playful joke. Owing to the belief of medico-legal issues and socio-psychological circumstances about the ano-rectal injury, initial approach to the medical facilities might be delayed, causing a delayed presentation and poor prognosis. We report an incident of a young male who presented with tension pneumoperitoneum causing abdominal compartment syndrome with fecal peritonitis due to forceful passing of high-pressure air through his anus. An initial decompression of the abdomen with a wide-bore needle was done at the emergency room. An emergency laparotomy with a primary repair of the rectal perforation by two layered sutures was done followed by a loop colostomy, 10 cm proximal to the injury. Colostomy closure was performed after 4 weeks. Post-operative recovery period was uneventful.

Transfusions with laboratory-grown red blood cells: a new development in science.

It is inevitable to anticipate the development of laboratory abilities and their involvement in clinical research in a fast-paced world. The RESTORE study is one such incident that has drawn the interest of various specialists. Red blood cells (RBCs) that have been generated in a laboratory have been transfused into a volunteer in this trial. To our knowledge, this procedure was the first to deliver laboratory-grown cells to another individual through a blood transfusion, which is an advancement in laboratory innovations. The purpose of the research was to determine how long a mini-transfusion of up to two teaspoons or 10 mL of laboratory-grown RBCs will persist in the body in comparison with an equivalent quantity of regular cells from the same donor. Assuming the process can be scaled up to a standard transfusion, this approach is advantageous because it can address the shortage of donors for those with rare blood types. Laboratory-grown blood cells are anticipated to last longer and perform better, which is another benefit to be noticed. This study represents a tremendous advancement in scientific innovation and teamwork while providing high-quality care to those who need it the most, although additional trials are required before clinical usage.

Monkeypox Epidemic: A Throwback From Smallpox Eradication.

The emergence of microbial diseases has become a major concern for humans. In the recent past, we have noticed the emergence and re-emergence of several microbes that include coronaviruses (severe acute respiratory syndrome coronavirus {SARS-CoV}, Middle-East respiratory syndrome coronavirus {MERS-CoV}, SARS-CoV-2), and others like Zika virus, Nipah virus, Influenza virus, and Ebola virus. These microbes have been noted to spill over from animals into humans. Several such microbes which were previously restricted to wild animals are now becoming responsible for infections in humans and have spread across the borders and resulted in pandemics. It has been more than two years since the discovery of the novel SARS-CoV-2 virus responsible for the coronavirus disease 2019 (COVID-19), and we are still struggling to cope-up with it and live normal lives. Recently, the monkeypox virus, which was confined to West and Central African countries, and caused endemic infections in monkeys and humans was associated with human infections in non-endemic regions like the United States of America (USA) and more than 30 other countries. Therefore, in this editorial, we attempt to put the spotlight on the monkeypox virus that is currently threatening to cause another widespread pandemic.

Activities of Serum Ferritin and Treatment Outcomes Among COVID-19 Patients Treated With Vitamin C and Dexamethasone: An Uncontrolled Single-Center Observational Study.

Background The fatal outcomes by COVID-19 are accompanied by cytokine storm syndrome, and thereby it is reported that disease severity is dependent on the cytokine storm syndrome. This cytokine storm can be assessed by evaluating the serum ferritin levels. The objective of this study was to assess the activities of serum ferritin and treatment outcomes among COVID-19 patients who were treated with dexamethasone and vitamin C.  Materials and methods A single-center, prospective, observational study was conducted among SARS-CoV-2 infected patients from July 2020 to August 2020. The diagnosis was confirmed by real-time polymerase chain reaction (RT-PCR) and computed tomography (CT) imaging of the lungs. Serum ferritin levels were compared with the treatment outcomes of COVID-19 positive patients who were treated with dexamethasone and vitamin C. Results A total of 50 COVID-19 patients were included in the study. The mean age was 41.70 years. The recovery rate (94%) was remarkably high and is a good sign of COVID 19 treatment with vitamin C and dexamethasone as key modalities. The mean serum ferritin levels among recovered and expired patients were 478.81 ng/ml and 1410 ng/ml, respectively. Conclusion The serum activities of ferritin were markedly increased in COVID-19 patients who could not survive as compared to the patients who finally recovered from the infection.

High Dose Steroid Therapy to Prevent Severe Hypoxia in COVID-19 Patients: A Potential Solution for Low Resource Clinical Setting.

Coronavirus disease 2019 (COVID-19) can lead to severe respiratory failure; about 5%-10% of patients progress to severe pneumonia and respiratory distress, leading to multi-system failure. Dexamethasone helped to prevent mortality in COVID-19 patients. Low resource population in developing countries has limited access to critical care, but they do have access to oral and IV corticosteroids, anti-hyperglycemic agents, and anticoagulants. We report two patients with severe COVID-19 successfully treated with a high dose of methylprednisolone therapy. Early intervention with high dose corticosteroids in COVID-19 patients could be a solution for pacifying cytokine storms and reducing morbidity and mortality.