Genome sequence, antibiotic resistance genes, and plasmids in a monophasic variant of Salmonella typhimurium isolated from retail pork.

A Salmonella isolate from retail pork was whole genome sequenced using Illumina NovaSeq6000, with a 5,320,119 bp genome and 51.06% GC content. Several antibiotic resistance genes and plasmids, including blaTEM-1, aac(6')-IIc, IncHI2, and p0111 were obtained from subsequent analysis. These findings provide vital insights into generic determinants of antimicrobial resistance (AMR) in this foodborne pathogen.

Mortality of in-hospital cardiac arrest among patients with and without preceding sepsis: A national inpatient sample analysis.

INTRODUCTION: The impact of preceding sepsis on in-hospital cardiac arrest (IHCA)-related mortality has not been established. This study aimed to determine the association between IHCA-related mortality and sepsis. METHODS: This retrospective study used the National Inpatient Sample data from 01/2017 to 12/2019. The study included adults (≥18 years) who suffered from IHCA. The study classified cardiac arrest rhythms as ventricular tachycardia/ventricular fibrillation or pulseless electronic activity/asystole. We compared the IHCA-related in-hospital mortality between sepsis and non-sepsis groups in all patients and subgroups divided by cardiac arrest rhythm and age. Multivariable logistic regression analysis was performed to assess the independent association between sepsis and in-hospital mortality. RESULTS: A total of 357,850 hospitalizations who suffered from IHCA were identified, with sepsis present in 17.6% of patients. IHCA-related in-hospital mortality was 84.8% in sepsis and 68.4% in non-sepsis-related hospitalizations (p < 0.001). IHCA-related in-hospital mortality was higher in sepsis than in non-sepsis groups, regardless of age or cardiac arrest rhythms. In multivariable logistic regression analysis, sepsis was significantly associated with higher mortality with an odds ratio of 2.27 (95% confidence interval: 2.07-2.50, p < 0.001). CONCLUSION: Sepsis was associated with higher in-hospital cardiac arrest mortality compared to non-sepsis cases, regardless of age and cardiac rhythm.

A natural small molecule-mediated inhibition of alpha-synuclein aggregation leads to neuroprotection in Caenorhabditis elegans.

Small molecules are being explored intensively for their applications as therapeutic molecules in the management of metabolic and neurological disorders. The natural small molecules can inhibit protein aggregation and underlying cellular pathogenesis of neurodegenerative diseases involving multi-factorial mechanisms of action. Certain natural small molecular inhibitors of pathogenic protein aggregation are highly efficient and have shown promising therapeutic potential. In the present study, Shikonin (SHK), a natural plant-based naphthoquinone has been investigated for its aggregation inhibition activity against α-synuclein (α-syn) and the neuroprotective potential in Caenorhabditis elegans (C. elegans). SHK significantly inhibited aggregation of α-syn at sub-stochiometric concentrations, delayed the linear lag phase and growth kinetics of seeded and unseeded α-syn aggregation. The binding of SHK to the C-terminus of α-syn maintained α-helical and disordered secondary structures with reduced beta-sheet content and complexity of aggregates. Further, in C. elegans transgenic PD models, SHK significantly reduced α-syn aggregation, improved locomotor activity and prevented dopaminergic (DA) neuronal degeneration, indicating the neuroprotective role of SHK. The present study highlights the potential of natural small molecules in the prevention of protein aggregation that may further be explored for their therapeutic efficacy in the management of protein aggregation and neurodegenerative diseases.

In-silico screening of plant-derived antivirals against main protease, 3CLpro and endoribonuclease, NSP15 proteins of SARS-CoV-2.

Novel Coronavirus or SARS-CoV-2 outbreak has developed a pandemic condition all over the world. The virus is highly infectious and spreads by human to human local transmission mode. Till date, there is no vaccination or drugs been approved for the treatment by the World Health Organisation. Henceforth, the discovery of the potential drugs is an urgent and utmost requirement for the medical fraternity. Since, the side effects of plant-derived compounds will be lower compared to synthetic/chemical drugs. The Main protease (3CLpro or NSP5) and endoribonuclease (NSP15) proteins are necessity for viral replication and its survival in the host cell. In the present study, in-silico approach of drug development was used to search for potential antiviral plant-derived compounds as inhibitors against SARS-CoV-2 replication proteins. Eight plant-derived compounds of which the antiviral activity was known and available, and two reported drugs against SARS-CoV-2 selected for the molecular docking analysis. The docking results suggested that bisdemethoxycurcumin, demethoxycurcumin, scutellarin, quercetin and myricetin showed least binding energy, i.e., greater than -6.5 Kcal/mol against 3CLpro and endoribonuclease of SARS-CoV-2. Further studies of ADME-Tox and bioavailability of drugs were also performed that exhibited efficient parameters of drug likeness. Molecular dynamics simulation calculations were performed for the most negative binding affinity of the compound to evaluate the dynamic behavior,and stability of protein-ligand complex. Our findings suggest that these compounds could be potential inhibitors of SARS-CoV-2 main protease and endoribonuclease. However, further in-vitro and pre-clinical experiments would validate the potential inhibitors of SARS-CoV-2 proteins.

Metastatic cholangiocarcinoma in a patient with undiagnosed Wilson disease.

Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy. Although the frequency of malignancy is generally increased in chronic liver disease, CC rarely presents in Wilson disease (WD). The incidence of hepatic malignancy in WD is only 1.2%, with CC accounting for 0.5%. A 66 year old male with history of hypertension, diabetes, and compensated cryptogenic cirrhosis presented with acute onset dyspnea and pleuritic chest pain. He was incidentally found to have a sizeable mass in the right hepatic lobe. Ultimately, a liver biopsy revealed dense demoplasia and increased mucin production, consistent with diagnosis of CC. Biopsy also demonstrated increased copper deposition consistent with WD, explaining the patient's underlying cirrhosis. Unlike other forms of chronic liver disease where incidence of liver cancer is increased, the lower rate of malignancy seen in WD may be explained by a protective effect of copper in WD. Copper acts to both directly stabilize DNA and inhibit angiogenesis. In this case, it is possible that the degree of copper deposition in his liver was mild, causing cirrhosis and the chronic liver inflammation that caused his CC. However, it may not have been sufficient to "protect" against development of CC.

Triple Tick Attack.

Tick-borne diseases are frequently seen in tick-inhabited areas. Lyme disease is the most common tick-borne illness. However, patients with co-infections can present with nonspecific symptoms, which can make the diagnosis far more challenging. We present a case of triple infection with babesiosis, Lyme disease, and anaplasmosis treated with antibiotics and red blood cell (RBC) exchange (erythrocytapheresis). A 74-year-old, avid female gardener presented with one week of progressive dyspnea, cough with mucoid expectoration, and fatigue. On presentation, she was afebrile, hypotensive, and tachycardic. General examination was significant for altered mental status, dyspnea, pallor, and peripheral edema. Lung examination was remarkable for bibasilar crackles. Pertinent laboratory findings were significant for hemolytic anemia and thrombocytopenia. A peripheral blood smear revealed the presence of intracytoplasmic parasites consistent with Babesia. The patient was started on azithromycin and atovaquone. Doxycycline was added empirically for Lyme disease, which was later confirmed by serology. In addition, Anaplasma titers were also positive. Further investigation revealed that the parasitic load was 9.04%, and RBC exchange (erythrocytapheresis) was performed for severe babesiosis. Repeat laboratory tests demonstrated an inadequate reduction in parasitic load (6.54%), requiring a second round of RBC exchange. Antimicrobials were changed to clindamycin, quinine, and doxycycline for a total of 14 days. There was an improvement in the patient's anemia and thrombocytopenia along with clinical improvement.

Differential adhesion molecule expression during murine embryonic stem cell commitment to the hematopoietic and endothelial lineages.

Mouse embryonic stem cells (ESC) make cell fate decisions based on intrinsic and extrinsic factors. The decision of ESC to differentiate to multiple lineages in vitro occurs during the formation of embryoid bodies (EB) and is influenced by cell-environment interactions. However, molecular mechanisms underlying cell-environmental modulation of ESC fate decisions are incompletely understood. Since adhesion molecules (AM) influence proliferation and differentiation in developing and adult tissues, we hypothesized that specific AM interactions influence ESC commitment toward hematopoietic and endothelial lineages. Expression of AM in the adherens, tight and gap junction pathways in ESC subpopulations were quantified. E-cadherin (E-cad), Claudin-4 (Cldn4), Connexin-43 (Cx43), Zona Occludens-1 (ZO-1) and Zona Occludens-2 (ZO-2) transcript levels were differentially expressed during early stages of hematopoietic/endothelial commitment. Stable ESC lines were generated with reduced expression of E-cad, Cldn4, Cx43, ZO-1 and ZO-2 using shRNA technology. Functional and phenotypic consequences of modulating AM expression were assessed using hematopoietic colony forming assays, endothelial sprouting assays and surface protein expression. A decrease in E-cad, Cldn4, Cx43 and ZO-1 expression was associated with less commitment to the hematopoietic lineage and increased endothelial differentiation as evidenced by functional and phenotypic analysis. A reduction in ZO-2 expression did not influence endothelial differentiation, but decreased hematopoietic commitment two-fold. These data indicate that a subset of AM influence ESC decisions to commit to endothelial and hematopoietic lineages. Furthermore, differentially expressed AM may provide novel markers to delineate early stages of ESC commitment to hematopoietic/endothelial lineages.