The earliest settlers of Mesoamerica date back to the late Pleistocene.

Preceramic human skeletal remains preserved in submerged caves near Tulum in the Mexican state of Quintana Roo, Mexico, reveal conflicting results regarding 14C dating. Here we use U-series techniques for dating a stalagmite overgrowing the pelvis of a human skeleton discovered in the submerged Chan Hol cave. The oldest closed system U/Th age comes from around 21 mm above the pelvis defining the terminus ante quem for the pelvis to 11311±370 y BP. However, the skeleton might be considerable older, probably as old as 13 ky BP as indicated by the speleothem stable isotope data. The Chan Hol individual confirms a late Pleistocene settling of Mesoamerica and represents one of the oldest human osteological remains in America.

Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid.

Peritonitis remains a major cause of morbidity and mortality during chronic peritoneal dialysis (PD). Glucose-based PD fluids reduce immunological defenses in the peritoneal cavity. Low concentrations of peritoneal extracellular glutamine during PD may contribute to this immune deficit. For these reasons we have developed a clinical assay to measure the function of the immune-competent cells in PD effluent from PD patients. We then applied this assay to test the impact on peritoneal immune-competence of PD fluid supplementation with alanyl-glutamine (AlaGln) in 6 patients in an open-label, randomized, crossover pilot trial (EudraCT 2012-004004-36), and related the functional results to transcriptome changes in PD effluent cells. Ex-vivo stimulation of PD effluent peritoneal cells increased release of interleukin (IL) 6 and tumor necrosis factor (TNF) α. Both IL-6 and TNF-α were lower at 1 h than at 4 h of the peritoneal equilibration test but the reductions in cytokine release were attenuated in AlaGln-supplemented samples. AlaGln-supplemented samples exhibited priming of IL-6-related pathways and downregulation of TNF-α upstream elements. Results from measurement of cytokine release and transcriptome analysis in this pilot clinical study support the conclusion that suppression of PD effluent cell immune function in human subjects by standard PD fluid is attenuated by AlaGln supplementation.

Role of nonsustained ventricular tachycardia and programmed ventricular stimulation for risk stratification in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: The prognostic role of asymptomatic nonsustained ventricular tachycardia (NSVT) and programmed ventricular stimulation (PVS) in patients with idiopathic dilated cardiomyopathy (IDC) remains controversial. METHODS: The prognostic significance of ventricular arrhythmias, ejection fraction, NYHA class, atrial fibrillation and age for overall and sudden death mortality was prospectively studied in 157 patients with IDC (group 1) free of documented sustained ventricular arrhythmia and syncope. In 99 patients with asymptomatic NSVT (group 2), PVS with 2 - 3 extrastimuli was performed. Non-inducible patients were discharged without specific antiarrhythmic therapy, whereas those with inducible monomorphic ventricular tachycardia were implanted with an ICD. RESULTS: In group 1, 48% of patients had NSVT. Overall and sudden death mortality were significantly higher in patients with NSVT (34.2 vs. 9.8%, p = 0.0001 and 15.8 vs. 3.7%, p = 0.0037; follow-up 22 +/- 14 months). Multivariate analysis revealed that NSVT independently predicts both overall and sudden death mortality (p = 0.0021 and.0221, respectively; adjusted for EF, NYHA class and age). In group 2, inducibility of sustained ventricular tachyarrhythmia was 7%, but sustained monomorphic VT occurred in 3% only. Two of 7 inducible patients experienced arrhythmic events during a follow-up of 25 +/- 21 months (positive predictive value 29%). Overall and sudden death mortality were 29% and 0% in the inducible group vs. 17 and 4% in the non-inducible group. Both overall and sudden death mortality were significantly lower in non-inducible patients from group 2 as compared to patients from group 1 with NSVT (p = 0.0043 and 0.0048), most likely due to a more common use of betablockers and a higher EF in the former group (p < 0.001, respectively). CONCLUSIONS: In patients with IDC, NSVT independently predicts both overall and sudden death mortality. Due to a low inducibility rate and a poor positive predictive value, PVS seems inappropriate for further arrhythmia risk assessment. However, in spite of documented NSVT, the incidence of SCD in patients on optimized medical treatment including betablockers seems to be very low, questioning the need for specific arrhythmia risk stratification.

Are electrophysiological studies needed prior to defibrillator implantation?

At present, patients with documented sustained VT or resuscitated cardiac arrest (CA) are treated with ICDs. The aim of this study was to retrospectively evaluate if a routine electrophysiological study should be recommended prior to ICD implantation. In 462 patients referred for ICD implantation because of supposedly documented VT (n = 223) or CA (n = 239), electrophysiological study was routinely performed. In 48% of the patients with CA, sustained VT or VF was inducible. Electrophysiological study suggested conduction abnormalities (n = 11) or supraventricular tachyarrhythmias (n = 3) in conjunction with severely impaired left ventricular function to have been the most likely cause of CA in 14 (5.9%) of 239 patients. Likewise, sustained VT was only inducible in 48% of patients with supposedly documented VT. Of these inducible VTs, nine were diagnosed as right ventricular outflow tract tachycardia or as bundle branch reentry tachycardia. Supraventricular tachyarrhythmias judged to represent the clinical event were the only inducible arrhythmia in 35 (16%) patients (AV nodal reentrant tachycardia [n = 7], AV reentry tachycardia [n = 4], atrial flutter [n = 19], and atrial tachycardia [n = 5]). Based on findings from the electrophysiological study, ICD implantation was withheld in 14 (5.9%) of 239 patients with CA and in 44 (19.7%) of 223 patients with supposedly documented VT. During electrophysiological study, VT or VF was only reproducible in about 50% of patients with supposedly documented VT or CA. Electrophysiological study revealed other, potentially curable causes for CA or supposedly documented VT in 12.6% (58/462) of all patients, indicating that ICD implantation can potentially be avoided or at least postponed in some of these patients. Based on these retrospective data, routine electrophysiological study prior to ICD implantation seems to be advisable.