Performance Characteristics of a Real-Time PCR Assay for Direct Detection of Streptococcus pneumoniae in Clinical Specimens.

Community-acquired pneumonia and complications, such as bacteremia and meningitis due to Streptococcus pneumoniae infection, still occur in at-risk populations, despite the availability of effective vaccines. Laboratory confirmation of S. pneumoniae remains challenging despite advances in blood culture techniques and the availability of nucleic acid-amplification tests.

A feasibility study on exhaled breath analysis using UV spectroscopy to detect COVID-19.

A 23-subject feasibility study is reported to assess how UV absorbance measurements on exhaled breath samples collected from silicon microreactors can be used to detect COVID-19. The silicon microreactor technology chemoselectively preconcentrates exhaled carbonyl volatile organic compounds and subsequent methanol elution provides samples for analysis. The underlying scientific rationale that viral infection will induce an increase in exhaled carbonyls appears to be supported by the results of the feasibility study.

Misdiagnosis of Clostridioides difficile Infections by Standard-of-Care Specimen Collection and Testing among Hospitalized Adults, Louisville, Kentucky, USA, 2019-2020.

Although Clostridioides difficile infection (CDI) incidence is high in the United States, standard-of-care (SOC) stool collection and testing practices might result in incidence overestimation or underestimation. We conducted diarrhea surveillance among inpatients >50 years of age in Louisville, Kentucky, USA, during October 14, 2019-October 13, 2020; concurrent SOC stool collection and CDI testing occurred independently. A study CDI case was nucleic acid amplification test‒/cytotoxicity neutralization assay‒positive or nucleic acid amplification test‒positive stool in a patient with pseudomembranous colitis.

Persistent SARS-CoV-2 Infection in a Multiple Sclerosis Patient on Ocrelizumab: A Case Report.

A 44-year-old female patient with multiple sclerosis (MS) treated with ocrelizumab was hospitalized with SARS-CoV-2 pneumonia three times over the course of five months, eventually expiring. Viral sequencing of samples from her first and last admissions suggests a single persistent SARS-CoV-2 infection. We hypothesize that her immunocompromised state, due to MS treatment with an immunosuppressive monoclonal antibody, prevented her from achieving viral clearance.

Development and Evaluation of a Fully Automated Molecular Assay Targeting the Mitochondrial Small Subunit rRNA Gene for the Detection of Pneumocystis jirovecii in Bronchoalveolar Lavage Fluid Specimens.

The fungal pathogen Pneumocystis jirovecii causes Pneumocystis pneumonia. Although the mitochondrial large subunit rRNA gene (mtLSU) is commonly used as a PCR target, a mitochondrial small subunit rRNA gene (mtSSU)-targeted MultiCode PCR assay was developed on the fully automated ARIES platform for detection of P. jirovecii in bronchoalveolar lavage fluid specimens in 2.

Detection of Ehrlichia spp. and Anaplasma phagocytophilum in whole blood specimens using a duplex real-time PCR assay on the ARIES instrument.

Cases of tick-borne diseases are increasing in the United States, and new tick-borne pathogen species causing human illness are being discovered. The specific etiology is generally difficult to diagnose based on clinical signs and symptoms alone, because of their generalized nature and often lack of a known tick bite. For some infections, such as Lyme disease and spotted fever group rickettsioses, serology remains the most appropriate laboratory diagnostic tool, but for others such as anaplasmosis, ehrlichiosis, and babesiosis, direct detection in the blood is preferred for rapid diagnosis.

Neuraminidase activity mediates IL-6 production by activated lupus-prone mesangial cells.

The development of nephritis is a leading cause of morbidity and mortality in lupus patients. Although the general pathophysiological progression of lupus nephritis is known, the molecular mediators and mechanisms are incompletely understood. Previously, we demonstrated that the glycosphingolipid (GSL) catabolic pathway is elevated in the kidneys of MRL/lpr lupus mice and human lupus patients with nephritis.

Loss of neutral ceramidase protects cells from nutrient- and energy -deprivation-induced cell death.

Sphingolipids are a family of lipids that regulate the cell cycle, differentiation and cell death. Sphingolipids are known to play a role in the induction of apoptosis, but a role for these lipids in necroptosis is largely unknown. Necroptosis is a programmed form of cell death that, unlike apoptosis, does not require ATP.

Repeated administration of low-dose cisplatin in mice induces fibrosis.

Cisplatin, a chemotherapeutic used for the treatment of solid cancers, has nephrotoxic side effects leading to acute kidney injury (AKI). Cisplatin cannot be given to patients that have comorbidities that predispose them to an increased risk for AKI. Even without these comorbidities, 30% of patients administered cisplatin will develop kidney injury, requiring the oncologist to withhold or reduce the next dose, leading to a less effective therapeutic regimen.

Kidney glycosphingolipids are elevated early in diabetic nephropathy and mediate hypertrophy of mesangial cells.

Glycosphingolipids (GSLs) play a role in insulin resistance and diabetes, but their role in diabetic nephropathy (DN) has received limited attention. We used 9- and 17-wk-old nondiabetic db/m and diabetic db/db mice to examine the role of GSLs in DN. Cerebrosides or monoglycosylated GSLs [hexosylceramides (HexCers); glucosyl- and galactosylceramides] and lactosylceramide (LacCers) were elevated in db/db mouse kidney cortices, specifically in glomeruli, and also in urine.

Glucose availability and glycolytic metabolism dictate glycosphingolipid levels.

Cancer therapeutics has seen an emergence and re-emergence of two metabolic fields in recent years, those of bioactive sphingolipids and glycolytic metabolism. Anaerobic glycolysis and its implications in cancer have been at the forefront of cancer research for over 90 years. More recently, the role of sphingolipids in cancer cell metabolism has gained recognition, notably ceramide's essential role in programmed cell death and the role of the glucosylceramide synthase (GCS) in chemotherapeutic resistance.

Sphingomyelin synthase 1 activity is regulated by the BCR-ABL oncogene.

Sphingomyelin synthase (SMS) produces sphingomyelin while consuming ceramide (a negative regulator of cell proliferation) and forming diacylglycerol (DAG) (a mitogenic factor). Therefore, enhanced SMS activity could favor cell proliferation. To examine if dysregulated SMS contributes to leukemogenesis, we measured SMS activity in several leukemic cell lines and found that it is highly elevated in K562 chronic myelogenous leukemia (CML) cells.

Sphingomyelin synthases regulate protein trafficking and secretion.

Sphingomyelin synthases (SMS1 and 2) represent a class of enzymes that transfer a phosphocholine moiety from phosphatidylcholine onto ceramide thus producing sphingomyelin and diacylglycerol (DAG). SMS1 localizes at the Golgi while SMS2 localizes both at the Golgi and the plasma membrane. Previous studies from our laboratory showed that modulation of SMS1 and, to a lesser extent, of SMS2 affected the formation of DAG at the Golgi apparatus.

Role of sphingomyelin synthase in controlling the antimicrobial activity of neutrophils against Cryptococcus neoformans.

The key host cellular pathway(s) necessary to control the infection caused by inhalation of the environmental fungal pathogen Cryptococcus neoformans are still largely unknown. Here we have identified that the sphingolipid pathway in neutrophils is required for them to exert their killing activity on the fungus. In particular, using both pharmacological and genetic approaches, we show that inhibition of sphingomyelin synthase (SMS) activity profoundly impairs the killing ability of neutrophils by preventing the extracellular release of an antifungal factor(s).

Sphingomyelin synthases regulate production of diacylglycerol at the Golgi.

SMS [SM (sphingomyelin) synthase] is a class of enzymes that produces SM by transferring a phosphocholine moiety on to ceramide. PC (phosphatidylcholine) is believed to be the phosphocholine donor of the reaction with consequent production of DAG (diacylglycerol), an important bioactive lipid. In the present study, by modulating SMS1 and SMS2 expression, the role of these enzymes on the elusive regulation of DAG was investigated.

Role of L-carnitine in the modulation of immune response in aged rats.

Background: The immune system undergoes alterations in functions with aging which results in progressive deterioration in the ability to respond to infection. The importance of nutrients in regulating immune responses has widened attempts on interventions that improve immune functions with aging. L-carnitine serves as a vital factor in the mitochondrial transport of fatty acids, a process essential for fatty acid oxidation and energy release.

Emerging role of Centella asiatica in improving age-related neurological antioxidant status.

Free radicals have been hypothesized to play an important role in ageing process. There exists an imbalance between free radical production and antioxidant defense mechanism, which may lead to cell death during ageing. Our study was designed to determine whether extract of Centella asiatica, an antioxidant, when administered orally (300 mg/kg body weight/day) for 60 days would prevent age-related changes in antioxidant defense system, lipid peroxidation (LPO) and protein carbonyl (PCO) content in rat brain regions such as cortex, hypothalamus, striatum, cerebellum and hippocampus.

Arsenic intoxication-induced reduction of glutathione level and of the activity of related enzymes in rat brain regions: reversal by DL-alpha-lipoic acid.

The purpose of this study was to examine the effects of DL: -alpha-lipoic acid (LA) on arsenic (As) induced alteration of glutathione (GSH) level and of the activity of glutathione-related enzymes-glutathione peroxidase (GSH-Px), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH)-in rat brain regions (cortex, hypothalamus, striatum, cerebellum and hippocampus). Male Wistar rats of 150+/-10 g weight were divided into four groups: control and three experimental groups supplemented with arsenic (sodium arsenite) alone (100 ppm mixed in drinking water), lipoic acid alone (70 mg kg(-1) body weight), arsenic plus lipoic acid (100 ppm arsenic in drinking water plus 70 mg lipoic acid kg(-1) body weight). The arsenic content of brain regions was found to increase with the administration of sodium arsenite.

Age-associated decreased activities of mitochondrial electron transport chain complexes in heart and skeletal muscle: role of L-carnitine.

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), considered as the pathogenic agent of many diseases and aging. L-Carnitine (4-N-trimethylammonium-3-hydroxybutric acid) plays an important role in transport of fatty acid from cytoplasm to mitochondria for energy production. Previous studies in our laboratory reported L-carnitine as a free radical scavenger in aged rats.