Microbiome-driven alterations in metabolic pathways and impaired cognition in aged female TgF344-AD rats.

Alzheimer's disease (AD) not only affects cognition and neuropathology, but several other facets capable of negatively impacting quality of life and potentially driving impairments, including altered gut microbiome (GMB) composition and metabolism. Aged (20 + mo) female TgF344-AD and wildtype rats were cognitively characterized on several tasks incorporating several cognitive domains, including task acquisition, object recognition memory, anxiety-like behaviors, and spatial navigation. Additionally, metabolic phenotyping, GMB sequencing throughout the intestinal tract (duodenum, jejunum, ileum, colon, and feces), neuropathological burden assessment and marker gene functional abundance predictions (PICRUSt2) were conducted. TgF344-AD rats demonstrated significant cognitive impairment in multiple domains, as well as regionally specific GMB dysbiosis. Relationships between peripheral factors were investigated using Canonical Correspondence Analysis (CCA), revealing correlations between GMB changes and both cognitive and metabolic factors. Moreover, communities of gut microbes contributing to essential metabolic pathways were significantly altered in TgF344-AD rats. These data indicate dysbiosis may affect cognitive outcomes in AD through alterations in metabolism-related enzymatic pathways that are necessary for proper brain function. Moreover, these changes were mostly observed in intestinal segments required for carbohydrate digestion, not fecal samples. These data support the targeting of intestinal and microbiome health for the treatment of AD.

Lyme-Associated Pericarditis: A Case Report and Literature Review.

Lyme disease is caused by Borrelia burgdorferi (B. burgdorferi), which is a spirochete transmitted by ticks of the genus Ixodes. Complications related to the cardiovascular system usually occur in the early phase of infection, and the most common cardiovascular complication of Lyme disease is atrioventricular block, especially third-degree heart block. We report a case of a young Caucasian male patient who presented to the emergency department (ED) with complaints of chest pain and shortness of breath. Initial investigations, including chest X-ray, were negative. An EKG revealed ST elevation and PR depression with troponin elevation. The echocardiogram showed a normal ejection fraction with no pericardial effusion. Skin examination was positive for erythema migrans concerning Lyme. Initial Lyme testing was negative in the patient and it should be repeated after four to six weeks, according to the guidelines. This case report highlights the importance of keeping the differentials broad in these patients even if the initial testing is negative, especially since misdiagnosis or delayed diagnosis can cause cardiac complications.

Selinexor for the treatment of patients with relapsed or refractory multiple myeloma.

OBJECTIVE: Multiple myeloma cells resist standard therapies due to overexpression of the transport protein, exportin 1. Selinexor is a novel drug that targets the Exportin 1 protein in these cells. DATA SOURCE: A comprehensive search was done, and data showing the efficacy and safety of selinexor in relapsed/refractory multiple myeloma was collected using PubMed, Google Scholar, and clincialtrials.gov. DATA SUMMARY: Results from the clinical trials STORM, BOSTON, and STOMP were included. Parts I and II of the STORM trial revealed a progression-free survival (PFS) of 4.7 and 3.7 months, a median duration of response of 6.2 and 4.4 months, and an overall survival of 7.3 and 8.4 months, respectively. BOSTON trial's SVd arm (selinexor, bortezomib, and dexamethasone) had a median follow-up period of 13.2 months and an mPFS of 13.93 months. The Vd arm (bortezomib and dexamethasone) had a median follow-up duration of 16.5 months and an mPFS of 9.46 months. The STOMP trial is still active and has limited data available. The SKd arm (selinexor, carfilzomib, and dexamethasone) reported an overall response rate of 66.7% in patients with triple refractory multiple myeloma, and 82% in patients with high-risk cytogenetics. The SPd arm (selinexor, pomalidomide, and dexamethasone) shows an overall response rate of 54.30% in pomalidomide naïve-nonrefractory, 35.70% in pomalidomide refractory and 60% in those dosed at RP2D. SRd arm (selinexor, lenalidomide, and dexamethasone) shows an overall response rate of 91.7% in lenalidomide naïve and 12.5% in lenalidomide refractory patients. SVd (selinexor, bortezomib, and dexamethasone) arm reported an overall response rate of 63% in all patients while the SDd arm (selinexor, daratumumab, and dexamethasone) showed an overall response rate of 73%. CONCLUSION: To improve the outcome of patients with relapsed/refractory multiple myeloma, it is critical to develop new therapies, assess potential therapeutic synergies, and overcome drug resistance by determining the efficacy of multiple myeloma therapies across multiple disease subgroups.

The Rationale for Using Corticosteroids in COVID-19 Encephalopathy: Lessons From a Case Report With Evidence From Literature.

The coronavirus disease 2019 (COVID-19) virus primarily affects the pulmonary system, but neurological manifestations and complication of COVID-19 has been reported in abundance in the literature. We present a case of a middle-aged Caucasian male who was brought to the emergency department for altered mental status. His chief complaints were neurological rather than respiratory. A positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) nasal swab confirmed the diagnosis. Brain imaging showed mildly dilated ventricles with no other acute findings. As the patient did not require oxygen, he was treated with remdesivir alone without corticosteroids, which is also a precipitating factor of psychosis but, unfortunately, thickly used in practice. That led to remarkable results in full recovery without exposing the patient to steroid therapy. We strongly believe that remdesivir alone is sufficient in treating COVID-19-induced encephalopathy in a patient who does not require oxygen, and evidence supports this practice.

An Overview of Systemic Lupus Erythematosus (SLE) Pathogenesis, Classification, and Management.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multisystem involvement. It is multifactorial and involves epigenetic, genetic, ecological, and environmental factors. Primarily it leads to activation of both innate and adaptive immunity, which consequently leads to autoreactive B cell activation by T cells and leads to immune complexes deposition in tissues leading to an autoimmune cascade that may be limited to the single organ or can cause a widespread systemic involvement. SLE is heterogeneous in presentation, with a broad spectrum of clinical manifestations ranging from clinically mild self-resolving symptoms to severe life-threatening organ involvement. Clinical and serological heterogeneity are critical features in SLE, posing a significant challenge in its diagnosis. Antinuclear antibodies (ANA) are the telltale serological marker in more than 95% of SLE patients. The improved set of European Alliance of Associations for Rheumatology (EULAR) classification enabled accurate diagnosis of SLE. The treatment focuses on remission, preventing organ damage, and improving the overall quality of life.

A Novel Protein Elicitor (PELL1) Extracted from Lecanicillium lecanii Induced Resistance against Bemisia tabaci (Hemiptera: Aleyrodidae) in Gossypium hirsutum L.

Protein elicitors play a key role in signaling or displaying plant defense mechanism and emerging as vital tools for biocontrol of insects. This study was aimed at the characterization of the novel protein elicitor isolated from entomopathogenic fungi Lecanicillium lecanii (V3) strain and its activity against whitefly, Bemisia tabaci, in cotton (Gossypium hirsutum L.). The sequence of purified elicitor protein showed 100% similarity with hypothetical protein LEL_00878 (Cordyceps confragosa RCEF 1005) (GenBank accession no. OAA81333.1). This novel protein elicitor has 253 amino acid residues and 762 bp with a molecular mass of 29 kDa. Their combatant protein was expressed in Escherichia coli using pET-28a (+) plasmid. Bioassay was revealed to quantify the impact of numerous concentrations of protein (i.e., 58.32, 41.22, and 35.41 µg/ml) on the fecundity rate of B tabaci on cotton plants. Bioassay results exhibited a significant effect (P ≤ 0.001) of all the concentrations of protein on the fecundity rate of B. tabaci. In addition, the gene expression analysis found a significant upregulation of the major genes associated with salicylic acid (SA) and jasmonic acid (JA) defense pathways in elicitor protein-treated plants. Our results showed that the potential application of novel protein elicitor derived from Lecanicillium lecanii will be used as future biointensive controlling approaches against whitefly, Bemisia tabaci.