New World University

• We designed a multi-epitope-based vaccine candidate against Mycobacterium tuberculosis (MTB) through an in-silico approach . • Immune simulation and docking with toll-like receptor 4 (TLR4) confirmed strong binding affinity and robust immunological properties. • Simulations predicted elevated levels of CD4 and CD8, T- lymphocytes, B- lymphocytes, plasma cells, and natural killer cells in secondary and tertiary immune responses. • While the construct showed high antigenicity and lacked allergenic or toxic properties, this study demonstrated the potentials of reverse vaccinology and in-silico methods for designing effective multi-epitope vaccines. Mycobacterium tuberculosis (MTB) remains a global health challenge, necessitating innovative strategies to enhance control and prevention. The emergence of drug-resistant MTB strains underscores the need for advanced tuberculosis (TB) vaccines beyond the Bacillus Calmette-Guérin (BCG). This study used computational approaches to design a multi-epitope MTB vaccine. Conserved antigenic proteins (PE_PGRS, ESAT-6, and CFP-10) were identified via MTB genome analyses from the NCBI database. Cytotoxic T cell (CTL), helper T cell (HTL), and B cell epitopes were predicted using the Immune Epitope Database (IEDB) and assembled with adjuvants and linkers to optimize stability and immunogenicity. The vaccine construct underwent rigorous assessments of epitope mapping, allergenicity, antigenicity, and tertiary structural modeling. Immune simulation and docking with toll-like receptor 4 (TLR4) confirmed strong binding affinity and robust immunological properties. The final construct, consisting of 512 amino acids and a molecular weight of 48,937.61 Da, demonstrated favorable structural and immunological attributes, including 91% of residues in acceptable regions (Ramachandran analysis). Simulations predicted elevated levels of CD4 and CD8 T lymphocytes, B lymphocytes, plasma cells, and natural killer cells in secondary and tertiary immune responses. Additionally, the vaccine was successfully cloned into an Escherichia coli (strain K12) pET-28a (+) plasmid for expression analysis. This study highlights the promise of reverse vaccinology and in-silico methods for designing effective multi-epitope vaccines. While the construct showed high antigenicity and lacked allergenic or toxic properties, further in vivo evaluations are crucial for confirming human efficacy.

The novel coronavirus disease 2019 (COVID-19) causes serious respiratory illness and related disorders. Vulnerable populations, including those with chronic obstructive pulmonary disease, heart disease, diabetes, chronic kidney disease, obesity, and the elderly, face an increased risk of severe complications. As the pandemic evolves, various diagnostic techniques are available to detect severe acute respiratory distress syndrome (SARS-CoV-2), including clinical presentation, rapid antigen/antibody testing, molecular testing, supplemental laboratory analysis, and imaging. Based on peer-reviewed data, treatment options include convalescent plasma transfusion, corticosteroids, antivirals, and immunomodulatory medications. Convalescent plasma therapy, historically used in outbreaks like Middle East respiratory syndrome, Ebola, and SARS, is suggested by the World Health Organization for critically ill COVID-19 patients when vaccines or antiviral drugs are unavailable. Neutralizing antibodies in convalescent plasma help control viral load and improve patient outcomes, especially when administered early, though effectiveness varies. The United States Food and Drug Administration has authorized its emergency use for severe COVID-19 cases, but potential risks such as transfusion reactions and transfusion-related acute lung injury require further investigation to establish definitive efficacy. Antiviral agents like Remdesivir, an adenosine nucleotide analog, inhibit viral RNA polymerase and have shown efficacy in reducing COVID-19 severity, leading to its emergency use authorization for hospitalized patients. Other antivirals like ritonavir, lopinavir, and umifenovir disrupt viral replication and entry, but their effectiveness against SARS-CoV-2 remains under investigation. Dexamethasone, a corticosteroid, has been used in critically ill COVID-19 patients to reduce inflammation and prevent respiratory failure, as shown in the RECOVERY trial. Other immunosuppressants like ruxolitinib, baricitinib, and colchicine help modulate the immune response, reducing cytokine storms and inflammation-related complications. However, corticosteroids carry risks such as hyperglycemia, immunosuppression, and delayed viral clearance, requiring careful administration. Systematic reviews of clinical studies revealed that hydroxychloroquine with or without azithromycin did not decrease viral load nor reduce the severity of symptoms, but increased mortality among acutely hospitalized patients. There was no improvement in patients’ clinical conditions after 15 days compared to standard treatment. The United States Food and Drug Administration has revoked the authorization for the use of hydroxychloroquine in COVID-19 patients due to the null benefit-risk balance. Monoclonal antibodies like itolizumab, gimsilumab, sarilumab, and tocilizumab are being studied for their ability to reduce the severe inflammatory response in COVID-19 patients, particularly cytokine release syndrome and acute respiratory distress syndrome. These antibodies target specific immune pathways to decrease pro-inflammatory cytokines, with some showing promising results in clinical trials, though their use remains under investigation. The Clustered Regularly Interspaced Short Palindromic Repeats/Cas13 family of enzymes, sequenced from many COVID-19-positive patients, can potentially inhibit SARS-CoV-2 replication, cleave the RNA genome, and aid in the amplification of the genome assay. Cas13 can also target emerging pathogens via an adeno-associated virus vector when delivered to the infected lungs. In addition to pharmacological agents, vaccines effectively prevent symptomatic infection, reduce hospitalizations, minimize mortality rates, and ultimately reduce the severity of the disease. This paper aims to explore the management of patients with underlying conditions who present with COVID-19 to lessen the burden on healthcare systems.

Metformin is a widely prescribed medication for the management of type 2 diabetes. It is known to have a high safety index; however, it can cause serious adverse effects such as lactic acidosis, particularly in patients with chronic kidney disease. Elderly patients are at higher risk of developing metformin-associated lactic acidosis (MALA) due to aging kidneys. We present an 82-year-old male with a past medical history of diabetes, stage 2 chronic kidney disease, atrial fibrillation on apixaban, stroke, and chronic stage 4 sacral decubitus ulcer who was sent to the emergency department (ED) for altered mental status. He was admitted to the intensive care unit for the management of septic shock, pulseless electrical activity (PEA) cardiac arrest, and acute hypoxemic respiratory failure requiring intubation. Laboratory tests showed lactic acidosis and anion gap metabolic acidosis in the absence of an infectious source. The patient had chronic kidney disease with acute renal failure on metformin. He was diagnosed with MALA. This case highlights the potential risks associated with metformin use in older adults with chronic kidney diseaseand acute kidney injury from infections, dehydration, and decreasing oral intake due to acute illness, aging, or dementia. There are expected physiological changes in the aging kidney, including cellular dysfunction and nephrosclerosis, that can cause unexpected kidney injury in older adults, causing their estimated glomerular filtration rate (eGFR) to drop acutely. Age-related changes in renal function and decreased clearance of drugs place elderly patients at higher risk of developing MALA. Guidelines for reducing or deprescribing metformin can be considered in older adults. This could prevent morbidity, mortality, and adverse outcomes in frail older adults with diabetes.

A cutaneous horn is a yellow or white-colored conical projection made up of complex keratin that arises from the surface of the skin. It is usually diagnosed clinically but requires histologic examination to rule out malignancy or determine the underlying lesion. Verruca vulgaris, a human papillomavirus-associated lesion, is a very common benign underlying lesion. We present a case of an 80-year-old female who presented with a cutaneous horn on a unique location, the proximal interphalangeal joint (PIP) of her left fourth digit. Post-excision biopsy revealed a diagnosis of a verruca vulgaris-associated cutaneous horn.

Omicron, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant that is now spreading across the world, is the most altered version to emerge so far, with mutations comparable to changes reported in earlier variants of concern linked with increased transmissibility and partial resistance to vaccine-induced immunity. This article provides an overview of the SARS-CoV-2 variant Omicron (B.1.1.529) by reviewing the literature from major scientific databases. Although clear immunological and clinical data are not yet available, we extrapolated from what is known about mutations present in the Omicron variant of SARS-CoV-2 and offer preliminary indications on transmissibility, severity, and immune escape through existing research and databases.

Though the modern era has proven to be reassuring with the advancement of perioperative care leading to improved survival, congenital heart disease (CHD) continues to underscore its significance in the lives of newborns and families worldwide. Particularly, CHD has disproportionately afflicted vulnerable minorities such as Black and Hispanic populations from the standpoint of ethnic disparities in mortality following heart surgery, increased resource utilization, and longer durations of stay. This study aims to identify and provide insight regarding the relationships between the aforementioned factors to develop targeted strategies of intervention to mitigate the outcomes for patients of these specific populations. Free, current peer-reviewed literature from databases such as the American Heart Association, The European Heart Journal, Science Direct, and PubMed regarding CHD, racial disparities, and socioeconomic variances were accessed. The study was narrowed to a patient population including only infants without chromosomal anomalies or those that passed away before hospital discharge. Having private insurance and maternal education showed positive correlations with positive outcomes of patients post congenital heart surgery. Teaching hospitals were linked with increased mortality and complications. Male infants showed higher rates of complications. Hispanics had increased odds of complications. Black patients had increased risk for failures in being rescued. Race plays a major role in the disparities in CHD, it is imperative to evaluate the socioeconomic contributors, surgical efforts, and provisions in place regarding minority patients. The apparency of these disparities, and willingness to invoke changes in practice has the potential for improvements in outcomes for these patients.

The coronavirus disease 2019 (COVID-19) outbreak was first reported in Wuhan, China, and was later reported to have spread throughout the world to create a global pandemic. As of August 18th, 2020, the coronavirus had spread to more than 216 countries with at least 21,756,357 confirmed cases, resulting in 771,635 deaths globally. Several countries declared this pandemic as a national emergency, forcing millions of people to go into lockdown. This unexpected imposed social isolation has caused enormous disruption of daily routines for the global community, especially children. Among the measures intended to reduce the spread of the virus, most schools closed, canceled classes, and moved it to home-based or online learning to encourage and adhere to social distancing guidelines. Education and learnings of 67.6% of students are impacted globally due to coronavirus in 143 countries. The transition away from physical classes has significantly disrupted the lives of students and their families, posing a potential risk to the mental well-being of children. An abrupt change in the learning environment and limited social interactions and activities posed an unusual situation for children's developing brains. It is essential and obligatory for the scientific community and healthcare workers to assess and analyze the psychological impact caused by the coronavirus pandemic on children and adolescents, as several mental health disorders begin during childhood. Countries across the globe, including the United States, are in the dilemma of determining appropriate strategies for children to minimize the psychological impact of coronavirus. The design of this review is to investigate and identify the risk factors to mental health and propose possible solutions to avoid the detrimental consequence of this crisis on the psychology of our future adult generations.

Stevens - Johnson Syndrome and Toxic Epidermal Necrolysis are adverse hypersensitivity reactions that affect the skin and mucous membranes. They are characterised by erythematous macules and hemorrhagic erosions of the mucous membranes. Epidermal detachments of varying degrees of severity also occur in these conditions. Various aetiologies are associated with these conditions, with adverse drug reaction being the most common. Though the worldwide incidence of these conditions is recorded as low, diverse types of medication are being observed to lead to these conditions. This review compiles information on the details of Stevens-Johnson syndrome and Toxic Epidermal Necrolysis, the pathophysiology, therapeutic management, and largely considers the drug-induced etiologies associated with these conditions.