The three-dimensional structure of human serum albumin has been solved at 6.0 angstrom (Å) resolution by the method of multiple isomorphous replacement. Crystals were grown from solutions of polyethylene glycol in the infrequently observed space group P 42 1 2 (unit cell constants a = b = 186.5 ± 0.5 Å and c = 81.0 ± 0.5 Å) and diffracted x-rays to lattice d -spacings of less than 2.9 A. The electron density maps are of high quality and revealed the structure as a predominantly α-helical globin protein in which the course of the polypeptide can be traced. The binding loci of several organic compounds have been determined.

The mechanism by which tumor necrosis factor-␣ (TNF) differentially modulates type I diabetes mellitus in the nonobese diabetic (NOD) mouse is not well understood. CD4 ؉ CD25 ؉ T cells have been implicated as mediators of self-tolerance. We show (i) NOD mice have a relative deficiency of CD4 ؉ CD25 ؉ T cells in thymus and spleen; (ii) administration of TNF or anti-TNF to NOD mice can modulate levels of this population consistent with their observed differential age-dependent effects on diabetes in the NOD mouse; (iii) CD4 ؉ CD25 ؉ T cells from NOD mice treated neonatally with TNF show compromised effector function in a transfer system, whereas those treated neonatally with anti-TNF show no alteration in ability to prevent diabetes; and (iv) repeated injection of CD4 ؉ CD25 ؉ T cells into neonatal NOD mice delays diabetes onset for as long as supplementation occurred. These data suggest that alterations in the number and function of CD4 ؉ CD25 ؉ T cells may be one mechanism by which TNF and anti-TNF modulate type I diabetes mellitus in NOD mice.

PurposeCurrent guidelines recommend maintaining a mean arterial pressure (MAP) ≥ 65 mmHg in septic patients. However, the relationship between hypotension and major complications in septic patients remains unclear. We, therefore, evaluated associations of MAPs below various thresholds and in-hospital mortality, acute kidney injury (AKI), and myocardial injury.MethodsWe conducted a retrospective analysis using electronic health records from 110 US hospitals. We evaluated septic adults with intensive care unit (ICU) stays ≥ 24 h from 2010 to 2016. Patients were excluded with inadequate blood pressure recordings, poorly documented potential confounding factors, or renal or myocardial histories documented within 6 months of ICU admission. Hypotension exposure was defined by time-weighted average mean arterial pressure (TWA-MAP) and cumulative time below 55, 65, 75, and 85 mmHg thresholds. Multivariable logistic regressions determined the associations between hypotension exposure and in-hospital mortality, AKI, and myocardial injury.ResultsIn total, 8,782 patients met study criteria. For every one unit increase in TWA-MAP < 65 mmHg, the odds of in-hospital mortality increased 11.4% (95% CI 7.8%, 15.1%, p < 0.001); the odds of AKI increased 7.0% (4.7, 9.5%, p < 0.001); and the odds of myocardial injury increased 4.5% (0.4, 8.7%, p = 0.03). For mortality and AKI, odds progressively increased as thresholds decreased from 85 to 55 mmHg.ConclusionsRisks for mortality, AKI, and myocardial injury were apparent at 85 mmHg, and for mortality and AKI risk progressively worsened at lower thresholds. Maintaining MAP well above 65 mmHg may be prudent in septic ICU patients.Electronic supplementary materialThe online version of this article (10.1007/s00134-018-5218-5) contains supplementary material, which is available to authorized users.

PurposeRecent data suggest that both elevated serum chloride levels and volume overload may be harmful during fluid resuscitation. The purpose of this study was to examine the relationship between the intravenous chloride load and in-hospital mortality among patients with systemic inflammatory response syndrome (SIRS), with and without adjustment for the crystalloid volume administered.MethodsWe conducted a retrospective analysis of 109,836 patients ≥18 years old that met criteria for SIRS and received fluid resuscitation with crystalloids. We examined the association between changes in serum chloride concentration, the administered chloride load and fluid volume, and the ‘volume-adjusted chloride load’ and in-hospital mortality.ResultsIn general, increases in the serum chloride concentration were associated with increased mortality. Mortality was lowest (3.7 %) among patients with minimal increases in serum chloride concentration (0–10 mmol/L) and when the total administered chloride load was low (3.5 % among patients receiving 100–200 mmol; P < 0.05 versus patients receiving ≥500 mmol). After controlling for crystalloid fluid volume, mortality was lowest (2.6 %) when the volume-adjusted chloride load was 105–115 mmol/L. With adjustment for severity of illness, the odds of mortality increased (1.094, 95 % CI 1.062, 1.127) with increasing volume-adjusted chloride load (≥105 mmol/L).ConclusionsAmong patients with SIRS, a fluid resuscitation strategy employing lower chloride loads was associated with lower in-hospital mortality. This association was independent of the total fluid volume administered and remained significant after adjustment for severity of illness, supporting the hypothesis that crystalloids with lower chloride content may be preferable for managing patients with SIRS.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-014-3505-3) contains supplementary material, which is available to authorized users.