Impact of COVID-19 lockdown on progressive multiple sclerosis patients

Neurological Sciences - The COVID-19 pandemic caused major changes in the lifestyle and in the access to health services worldwide. Progressive multiple sclerosis (pMS) patients are a vulnerable...     

ASO Visual Abstract: Time to Surgical Treatment and Facility Characteristics as Potential Drivers of Racial Disparities in Breast Cancer Mortality: Delay,Facilities, and Breast Cancer Mortality

Annals of Surgical Oncology -     

Harmful and protective roles of neutrophils in sepsis

The current studies demonstrate protective and harmful effects of neutrophils (PMN) during experimental sepsis after cecal ligation and puncture (CLP). It is known that CLP induces signaling defects in blood PMN. When PMN were depleted 12 h after CLP, there were dramatic reductions in levels of bacteremia, evidence for reduced liver and renal dysfunction, sharp reductions in serum levels of cytokines (IL-1beta, IL-6, IL-10, TNF-alpha, and IL-2), and improved survival. In contrast, PMN depletion before CLP resulted in substantial increases in bacteremia and no evidence for attenuation of liver and renal failure dysfunction. These data suggest that at the onset of sepsis, PMN are important in regulating the levels of bacteremia, whereas after the onset of sepsis, as they lose innate immune functions, their presence is associated with higher levels of bacteremia and intensified organ dysfunction.     

Basal ganglia hyperintensity on T1-weighted MRI in Rendu-Osler-Weber disease

The purpose of this study was to evaluate possible central nervous system (CNS) involvement in Rendu-Osler-Weber (ROW) disease in magnetic resonance imaging (MRI). Three patients with symptomatic ROW disease underwent brain MRI. Brain MRI depicted in all three of them increased signal intensity on T1-weighted images involving the globus pallidus and cerebral crura bilaterally. Laboratory studies of the two men showed iron deficiency anemia, while all three of them had normal liver function tests and increased manganese blood concentration. Gastroscopy and colonoscopy revealed a gastric and a cecal arteriovenous malformation (AVM) in the first one, while pulmonary and hepatic computed tomography (CT) angiography did not detect any intrahepatic shunts. Liver ultrasound in the second one revealed dilatation of intrahepatic artery branches consistent with intrahepatic shunts, while it was normal in the third patient. Chest radiographs were normal in all three patients. Pallidal T1 hyperintensity on T1-weighted imaging may be a biomarker of manganese overload in ROW disease.     

Relationship between Antimalarial Drug Activity, Accumulation, and Inhibition of Heme Polymerization in Plasmodium falciparum In Vitro

We have investigated the contribution of drug accumulation and inhibition of heme polymerization to the in vitro activities of a series of antimalarial drugs. Only those compounds exhibiting structural relatedness to the quinolines inhibited heme polymerization. We could find no direct correlation between in vitro activity against chloroquine-susceptible or chloroquine-resistant isolates and either inhibition of heme polymerization or cellular drug accumulation for the drugs studied. However, in vitro activity against a chloroquine-susceptible isolate but not a chloroquine-resistant isolate showed a significant correlation with inhibition of heme polymerization when the activity was normalized for the extent of drug accumulation. The importance of these observations to the rational design of new quinoline-type drugs and the level of agreement of these conclusions with current views on quinoline drug action and resistance are discussed.