A Rare Case of Toxic Myositis Associated with Influenza Vaccination.

The influenza vaccine is one of the most commonly administered vaccines worldwide, with a high safety profile. However, rare cases of serious adverse events have been reported in the literature. We report a 77-year-old male who presented with progressive weakness in the lower extremities shortly after receiving the Influenza vaccine. He was diagnosed with myositis involving the paraspinal and bilateral lower extremity muscles. He received treatment with high-dose steroids and taper with full recovery of his muscle weakness. Although the exact causal mechanism between the vaccine and the patient's myositis could not be established, surveillance for such rare adverse events can provide data for future vaccine safety improvement. Due to well-known benefits of the Influenza vaccine that far exceed the potential adverse effects, we strongly encourage the readers to continue their vaccine practices as per CDC guidelines.

IRF8-mutant B cell lymphoma evades immunity through a CD74-dependent deregulation of antigen processing and presentation in MHCII complexes.

The mechanism by which interferon regulatory factor 8 (IRF8) mutation contributes to lymphomagenesis is unknown. We modeled IRF8 variants in B cell lymphomas and found that they affected the expression of regulators of antigen presentation. Expression of IRF8 mutants in murine B cell lymphomas suppressed CD4, but not CD8, activation elicited by antigen presentation and downmodulated CD74 and human leukocyte antigen (HLA) DM, intracellular regulators of antigen peptide processing/loading in the major histocompatibility complex (MHC) II. Concordantly, mutant IRF8 bound less efficiently to the promoters of these genes. Mice harboring IRF8 mutant lymphomas displayed higher tumor burden and remodeling of the tumor microenvironment, typified by depletion of CD4, CD8, and natural killer cells, increase in regulatory T cells and T follicular helper cells. Deconvolution of bulk RNA sequencing data from IRF8-mutant human diffuse large B cell lymphoma (DLBCL) recapitulated part of the immune remodeling detected in mice. We concluded that IRF8 mutations contribute to DLBCL biology by facilitating immune escape.

The Use of CRISPR-Cas9 Genetic Technology in Cardiovascular Disease: A Comprehensive Review of Current Progress and Future Prospective.

Over the last century, there have been major landmark developments in the field of medicine, enabling us to control and cure various diseases on a larger scale. A few of these include the discovery of antibiotics, the development of vaccines, and the origin of organ and tissue transplants. The continued quest for innovation in microbiology and medicine has helped humankind save millions of lives and decrease morbidity at the global level. Genetic medicine has grown significantly in the last two decades and appears to be the next frontier of curative therapies for chronic diseases. One important landmark in genetic medicine is the development of CRISPR (clustered, regularly interspaced short palindromic repeats) technology. In this article, we describe the basic structure and function of the CRISPR-Cas9 system, which, simply put, consists of an RNA part and a protein. It works as a molecular scissor that can perform targeted cuts followed by repairs in and around the genes of interest to attain favorable translational outcomes. We focused on summarizing recent studies using CRISPR-Cas9 technology in diagnosing and treating cardiovascular disease. These studies are primarily experimental and limited to animal models. However, their results are promising enough to anticipate that this technology will undoubtedly be available in clinical medicine in the coming years. CRISPR-Cas9-mediated gene editing has been used to study and potentially treat congenital heart disease, hyperlipidemias, arrhythmogenic cardiomyopathies, and the prevention of ischemia-reperfusion injury. Despite the current progress, we recognize the several challenges this technology faces, including funding for research, improving precision and reproducible results for human subjects, and establishing protocols for ethical compliance so that it is acceptable to the scientific community and the general public.

New-onset seizures: an unusual neurologic manifestation of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory condition primarily affecting the musculoskeletal system but can often involve other organ systems as well. Rheumatoid meningitis is a rare central nervous system (CNS) manifestation of RA characterized by pachymeningeal and leptomeningeal enhancement. Herein, we present a case of a 64-year-old male who presented with left lower extremity weakness and witnessed seizures. The diagnostic work-up, including lumbar puncture, brain MRI and meningeal biopsy ruled out malignancy and were consistent with the diagnosis of rheumatoid meningitis. The patient was discharged on high-dose steroids along with anti-seizure medications. On subsequent follow-up visits, the patient remained seizure-free.

Health risks assessment and source admeasurement of potentially dangerous heavy metals (Cu, Fe, and Ni) in rapidly growing urban settlement.

Environmental contamination is a global challenge that impacts every aspect of ecosystem. The contaminants from anthropogenic or industrial trash continually recirculate into the environment, agricultural land, plants, livestock, and ultimately into humans by way of the food chain. After an increase in human and farmland animal deaths from illnesses due to contaminated drinking water, toxic metal water poisoning has remained a global concern. Diverse environmental and enforcement organisations have attempted to regulate the activities that serve as precursors to these heavy metals which have been proven ineffective. These unnecessary metals have severely hampered most biological processes. The presence of hazardous metals, which are harmful at extremely high levels and have a negative effect on the health of living bodies generally degrades the nutritional value of water. In order to evaluate the heavy metals (Cu, Ni, and Fe) toxicity of groundwater in pri-urban areas, the current study was conducted that have been considered as advance solution to tackle climate change which influence coastal ecosystem. Additionally, the impacts of soil and plant (spinach and brassica) contamination from groundwater were evaluated. The heavy metals were examined in the soil and groundwater samples (Pb, Fe and Ni). While Fe concentrations in water samples were found to be high as 1.978 mg/L as compared to Ni and Cu values low. According to WHO guidelines, the mean value of Fe exceeds the limit value. Similarly, Cu had a higher mean value (0.7 mg/L) in soil samples than other metals (Ni and Fe). In comparison to Ni and Cu, the Fe concentrations in spinach and brassica plants samples are greater, at 17.2 mg/L and 3.22 mg/L, respectively. The possible effects of metal poisoning of groundwater and plants on human health have been assessed using the Hazard Quotient (HQ), Evaluated Daily Intake (EDI), and Incremental Life Time Cancer Risk formulas (ILTCR). When drinking Ni-contaminated water, humans are more at risk of developing cancer (0.0031) than Fe and Cu. Metal concentrations in water and brassica showed substantially more scattered behaviour on the plot and no meaningful relationship, although PCA and masked matrix correlation showed a fair association between Ni and Cu in brassica (r2: 0.46) and Fe and Ni in spinach (r2: 0.31). According to the study's findings, it is anticipated that special management and groundwater monitoring will be needed in the examined area to reduce the health risks related to drinking water that has been contaminated with metals.

Reversible Cerebral Vasoconstriction Syndrome Associated With Oxybutynin Use; a Brief Review of Pathophysiology.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by reversible vasospasm of the central nervous system vasculature. It usually presents as a classic thunderclap headache, but complications like a stroke, seizure, or intracranial hemorrhage may occur at the onset. Most cases are linked temporally to secondary agents. The most common suggested mechanism underlying the RCVS is vascular tone dysregulation. Our report describes the RCVS incidence associated with oxybutynin use in a young female. We aim to describe the potential pathophysiology linking oxybutynin use and RCVS.

Arrhythmogenic Left Ventricular Cardiomyopathy Associated With a Phospholamban Gene Mutation in a Young Female: A Case Report and Literature Review.

Arrhythmogenic cardiomyopathy (ACM) is a myocardium disease characterized by phenotypic features of myocardial scarring due to fibrofatty myocardial replacement often associated with global or regional ventricular dysfunction. For years after arrhythmogenic right ventricular cardiomyopathy (ARVC) was first described, the left ventricle (LV) was generally considered normal or minimally involved. In recent years, however, LV involvement has been recognized. It usually presents with early-on arrhythmias more than heart failure symptoms compared to dilated cardiomyopathy. It can be right ventricular, biventricular, or left ventricular. The underlying pathophysiology involves either desmosomal or non-desmosomal mutations. Phospholamban (PLN) mutation is one of those and is associated with more severe arrhythmias and SCD. Primary prevention with ICD implantation should be considered in these patients, even the ones with an ejection fraction greater than 35%. In addition, if such patients progress to Stage D heart failure, they need to be evaluated for advanced heart failure therapies.

Lupus Podocytopathy: A Rare Cause of Nephrotic Syndrome in Patients with Systemic Lupus Erythematosus.

Lupus podocytopathy, a unique form of lupus nephritis, mimics minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS) and represents approximately 1% of lupus nephritis biopsies. Lupus podocytopathy is characterized by diffuse epithelial cell foot process effacement without immune complex deposition or with only mesangial immune complex deposition. We present the case of a young woman with systemic lupus erythematosus (SLE) who presented with nephrotic syndrome and acute kidney injury (AKI) and was subsequently diagnosed with lupus podocytopathy.

IRF8-mutant B cell lymphoma evades immunity through a CD74-dependent deregulation of antigen processing and presentation in MHC CII complexes.

In diffuse large B-cell lymphoma (DLBCL), the transcription factor IRF8 is the target of a series of potentially oncogenic events, including, chromosomal translocation, focal amplification, and super-enhancer perturbations. IRF8 is also frequently mutant in DLBCL, but how these variants contribute to lymphomagenesis is unknown. We modeled IRF8 mutations in DLBCL and found that they did not meaningfully impact cell fitness. Instead, IRF8 mutants, mapping either to the DNA-binding domain (DBD) or c-terminal tail, displayed diminished transcription activity towards CIITA, a direct IRF8 target. In primary DLBCL, IRF8 mutations were mutually exclusive with mutations in genes involved in antigen presentation. Concordantly, expression of IRF8 mutants in murine B cell lymphomas uniformly suppressed CD4, but not CD8, activation elicited by antigen presentation. Unexpectedly, IRF8 mutation did not modify MHC CII expression on the cell surface, rather it downmodulated CD74 and HLA- DM, intracellular regulators of antigen peptide processing/loading in the MHC CII complex. These changes were functionally relevant as, in comparison to IRF8 WT, mice harboring IRF8 mutant lymphomas displayed a significantly higher tumor burden, in association with a substantial remodeling of the tumor microenvironment (TME), typified by depletion of CD4, CD8, Th1 and NK cells, and increase in T-regs and Tfh cells. Importantly, the clinical and immune phenotypes of IRF8-mutant lymphomas were rescued in vivo by ectopic expression of CD74. Deconvolution of bulk RNAseq data from primary human DLBCL recapitulated part of the immune remodeling detected in mice and pointed to depletion of dendritic cells as another feature of IRF8 mutant TME. We concluded that IRF8 mutations contribute to DLBCL biology by facilitating immune escape.

Pembrolizumab-Induced Broken Heart Syndrome, Pneumonitis, and Hypophysitis Occurring Concurrently; A Deadly Triad.

Immune checkpoint inhibitors are novel medications used to treat a wide range of solid organ tumors and work by stimulating the cellular immune response. With their increasing use, more and more multiorgan side effects are reported in the literature. Prompt recognition of these findings is vital for the safe clinical use of these agents. Most side effects are immune-mediated injury, and the treatment involves stopping the ICI drug and systemic steroids. We report a case of a 72-year-old female treated with pembrolizumab monotherapy for non-small cell lung cancer. She presented for dyspnea and generalized weakness after the second session of pembrolizumab. She was found to have a triad of Takotsubo cardiomyopathy, hypophysitis, and pneumonitis. The patient was discharged home on steroids and heart failure treatment with the discontinuation of further sessions of pembrolizumab.

Heart Failure Associated With Mycoplasma Pneumoniae Infection, A Case and Review of Literature.

Mycoplasma pneumoniae is well known to cause pulmonary infection. However, it often has extrapulmonary manifestations as well. We diagnosed and treated a 41-year-old female who presented with symptoms of pneumonia along with multisystem involvement, including rash, acute hepatitis, and new onset heart failure that improved with steroids and doxycycline. Subsequent guideline-directed medical therapy for non-ischemic cardiomyopathy (NICM) coincided with the complete recovery of the left ventricular function in three months. We also did a brief literature review with similar prior reported cases.

Pakistan's Healthcare System: A Review of Major Challenges and the First Comprehensive Universal Health Coverage Initiative.

Each country's healthcare system has a different structure and functioning designed to meet the needs of its people utilizing the available resources. Due to ever-growing population needs and constantly emerging public health problems, it is vital for any healthcare system to be ready to adapt, recognize its limitations, and improve its flaws by learning from other healthcare models across the globe. In this article, we analyzed the significant challenges faced by Pakistan's healthcare system (PHS) and the first comprehensive initiative taken for universal health coverage in Pakistan. Inequitable distribution of resources, inadequate healthcare spending, non-adherence to preventative healthcare and brain drain are the major problems in the PHS. On the other hand, the recently introduced universal health coverage initiative, the Sehat Sahulat Program (SSP), can be considered one of the biggest achievements of the country's healthcare system.

An efficient spline technique for solving time-fractional integro-differential equations.

Spline curves are very prominent in the mathematics due to their simple construction, accuracy of assessment and ability to approximate complicated structures into interactive curved designs. A spline is a smooth piece-wise polynomial function. The primary goal of this study is to use extended cubic B-spline (ExCuBS) functions with a new second order derivative approximation to obtain the numerical solution of the weakly singular kernel (SK) non-linear fractional partial integro-differential equation (FPIDE). The spatial and temporal fractional derivatives are discretized by ExCuBS and the Caputo finite difference scheme, respectively. The present study found that it is stable and convergent. The validity of the current approach is examined on a few test problems, and the obtained outcomes are compared with those that have previously been reported in the literature.

Angioedema in the Absence of C1 Esterase Inhibitor Deficiency in a Young Patient With Anti-dsDNA Negative Lupus Nephritis.

Hereditary angioedema (HAE) is an autosomal dominant condition marked by a lack of functioning C1 esterase inhibitor (C1-INH). In contrast, acquired angioedema (AAE) due to a deficiency of C1 esterase inhibitor (AAE-C1-INH) may be the manifestation of an underlying lymphoproliferative, neoplastic, or autoimmune condition. Both are potentially fatal. The C1q protein is normal in HAE but low in AAE. A third mechanism has been reported to cause angioedema, especially in systemic lupus erythematosus (SLE) patients. AAE, which happens in association with SLE, may respond well to steroids. Here we present a case of AAE in a young female with SLE that led to upper airway compromise, requiring endotracheal intubation. Early detection and treatment of such cases can lead to an outstanding prognosis by preventing airway compromise and anoxic brain injury. Even though it is a condition of either very young or middle-aged patients, practitioners must be aware of this uncommon disease linked with SLE in adolescents and young adults.

Diagnostic and Therapeutic Challenges Associated With Left Ventricular Tumors.

Cardiac tumors are uncommon. Sometimes it is challenging to differentiate non-invasively between different kinds of cardiac tumors and thrombi, which is critical to dictate the subsequent treatment. In addition, not all high-risk cardiac tumors are amenable to surgical resection posing a therapeutic challenge. We report a case of cardiac papillary fibroelastoma in the left ventricular cavity with a 10-year follow-up, with no embolic complications.

Thyroid Cancer Presenting as Aspiration Pneumonia: A Tale of Retrosternal Goiters.

Abnormal enlargement of the thyroid gland is called goiter. Structurally, it can be nodular or diffuse. Usually, it presents as an anterior cervical mass; however, less commonly, it presents as a retrosternal mass causing symptoms of compression on the surrounding structures. Most patients with goiter are asymptomatic due to the euthyroid nature of the disease. However, sometimes they can be hypo or hyperthyroid depending on the etiology of the goiter. Here, we present the case of a patient without any previously known goiter who presented to the hospital with shortness of breath and was found to have hypoxic respiratory failure as his first noticed sign of thyroid disease. Diagnostic workup revealed retrosternal goiter causing compression effect on the esophagus and trachea resulting in dysphagia and aspiration. The patient was treated with feeding tube placement, followed by surgical resection of the mediastinal mass.

Ceftriaxone-Associated Severe Acute Hepatitis.

Drug-induced liver injury (DILI) is a common entity. Ceftriaxone is a well-tolerated parenteral antibiotic widely used for various bacterial infections. We report a patient who developed severe acute hepatitis following a single dose of 2 g ceftriaxone within one day. Apart from a fever of 101.9 F, no other insult was noted to explain his severe hepatocellular injury around the time of presentation. On stopping further ceftriaxone, his symptoms resolved, and liver enzymes normalized within a week. His Roussel Uclaf Causality Assessment Method (RUCAM) score was 6 which suggested DILI be a probable cause of his acute hepatitis. Further surveillance at a larger scale is needed to support evidence for this rare side effect.

Hydrothermally synthesized Ag-TiO2 nanofibers (NFs) for photocatalytic dye degradation and antibacterial activity.

This work successfully utilised eco-friendly green synthesis to produce Ag-TiO2 nanofibers (NFs). As pollution and energy limitations have become global issues, there is an ongoing need to develop more effective catalysts through straightforward and environmentally friendly methods. The Ag-TiO2 nanofibers (NFs) XRD pattern exhibits an anatase TiO2 and FCC crystal structure of Ag nanoparticles. The SEM investigation revealed a nanofiber-like surface morphology. The Ag-TiO2 nanofibers (NFs) exhibits an optical band gap energy is 2.5 eV. Methylene blue (MB), malachite green (MG), Congo red (CR), and crystal violet (CV) dye aqueous solutions were used to evaluate the photocatalytic performance of the synthesized Ag-modified TiO2 nanofibers (NFs) under direct sunlight irradiation. The effects of catalyst size on the efficient breakdown of MB dye were also investigated. The optimum catalyst concentration was found to be at 0.02 mg/mL. At 120 min of direct sunlight, the highest photosynthetic degradation efficiency (DE percentage) of 94% was achieved for MB dye. Ag-TiO2 nanofibers (NFs) have been demonstrated to have exceptional antibacterial activity against Gram-positive bacteria such as Staphylococcus aureus and Gram-negative bacteria E-Coli. Because of these great qualities, it seems likely that the Ag-TiO2 nanofibers (NFs) made could be a great photocatalyst for getting dye pollutants out of wastewater.

Utilization of diverse protein sources for the development of protein-based nanostructures as bioactive carrier systems: A review of recent research findings (2010-2021).

Consumer awareness of the relationship between health and nutrition has caused a substantial increase in the demand for nutraceuticals and functional foods containing bioactive compounds (BACs) with potential health benefits. However, the direct incorporation of many BACs into commercial food and beverage products is challenging because of their poor matrix compatibility, chemical instability, low bioavailability, or adverse impact on food quality. Advanced encapsulation technologies are therefore being employed to overcome these problems. In this article, we focus on the utilization of plant and animal derived proteins to fabricate micro and nano-particles that can be used for the oral delivery of BACs such as omega-3 oils, vitamins and nutraceuticals. This review comprehensively discusses different methods being implemented for fabrications of protein-based delivery vehicles, types of proteins used, and their compatibility for the purpose. Finally, some of the challenges and limitations of different protein matrices for encapsulation of BACs are deliberated upon. Various approaches have been developed for the fabrication of protein-based microparticles and nanoparticles, including injection-gelation, controlled denaturation, and antisolvent precipitation methods. These methods can be used to construct particle-based delivery systems with different compositions, sizes, surface hydrophobicity, and electrical characteristics, thereby enabling them to be used in a wide range of applications.

Carrier-Free Cross-linked Laccase Crystals for Biocatalytic Degradation of Textile Industrial Effluents.

Herein, laccase from Trametes versicolor was used to fabricate carrier-free cross-linked laccase crystals (CLLCs) and deployed as a robust catalyst for waste effluent treatment. The surface morphology and involvement of functional group attributes of CLLCs were scrutinized by scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). As fabricated CLLCs were subjected to kinetic characterization by assessing the effects of pH environment, thermal profile, and substrate (determination of Km and Vmax) on the activity. A fully characterized CLLCs fraction was used to treat synthetic dyes containing waste effluents taken from various industries, i.e., Chenab Textile Industry, M-tax, Sitara, and National Silk & Rayon Mills. Degradation profile revealed 36.8%, 27.6%, 39.9%, and 26.4% degradation of Chenab Textile Industry, M-tax, Sitara, and National Silk & Rayon Mills, respectively, by the free form of laccase, whereas the biocatalytic activity of CCLCs led to 78.6%, 75.6%, 85.5%, and 63.3% degradation of those effluents. The decrease in peak and mass region alongside the presence of new peaks in GC-MS affirms the effective decolorization of contaminated waste effluents. CLLCs retained over 70% and 50% of their degradation activity after 3 and 5 cycles, respectively. In conclusion, CLLCs might represent a robust bioprocess to improve the usability of laccase for various synthetic dyes containing waste effluents to diminish environmental pollution from the dye-based industries.