Towards Understanding the Effective Use of Antibiotics for Sepsis.

Background: The benefits of early antibiotics for sepsis have recently been questioned. Evidence for this mainly comes from observational studies. The only randomized trial on this subject, the Prehospital Antibiotics Against Sepsis (PHANTASi) trial, did not find significant mortality benefits from early antibiotics.

Supplemental Ascorbate Diminishes DNA Damage Yet Depletes Glutathione and Increases Acute Liver Failure in a Mouse Model of Hepatic Antioxidant System Disruption.

Cellular oxidants are primarily managed by the thioredoxin reductase-1 (TrxR1)- and glutathione reductase (Gsr)-driven antioxidant systems. In mice having hepatocyte-specific co-disruption of TrxR1 and Gsr (TrxR1/Gsr-null livers), methionine catabolism sustains hepatic levels of reduced glutathione (GSH). Although most mice with TrxR1/Gsr-null livers exhibit long-term survival, ~25% die from spontaneous liver failure between 4- and 7-weeks of age.

TrxR1, Gsr, and oxidative stress determine hepatocellular carcinoma malignancy.

Thioredoxin reductase-1 (TrxR1)-, glutathione reductase (Gsr)-, and Nrf2 transcription factor-driven antioxidant systems form an integrated network that combats potentially carcinogenic oxidative damage yet also protects cancer cells from oxidative death. Here we show that although unchallenged wild-type (WT), TrxR1-null, or Gsr-null mouse livers exhibited similarly low DNA damage indices, these were 100-fold higher in unchallenged TrxR1/Gsr-double-null livers. Notwithstanding, spontaneous cancer rates remained surprisingly low in TrxR1/Gsr-null livers.

Hepatocyte Hyperproliferation upon Liver-Specific Co-disruption of Thioredoxin-1, Thioredoxin Reductase-1, and Glutathione Reductase.

Energetic nutrients are oxidized to sustain high intracellular NADPH/NADP ratios. NADPH-dependent reduction of thioredoxin-1 (Trx1) disulfide and glutathione disulfide by thioredoxin reductase-1 (TrxR1) and glutathione reductase (Gsr), respectively, fuels antioxidant systems and deoxyribonucleotide synthesis. Mouse livers lacking both TrxR1 and Gsr sustain these essential activities using an NADPH-independent methionine-consuming pathway; however, it remains unclear how this reducing power is distributed.

Close Together, Far Apart: an Assessment of the Public Health Needs of Three Geographically Proximate Communities in Central Haiti.

Haiti, a country marked by extreme poverty and poor health, is also an active site for thousands of non-governmental organizations. The community needs assessment is an important tool that allows aid organizations to understand better community perspectives regarding health. In this study, 84 community members were interviewed across three geographically proximate communities in the Arcahaie region of Haiti to identify similarities and differences in community needs.