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Archaeological and genomic evidence suggest that modern Homo sapiens have roamed the planet for some 300-500 thousand years. In contrast, global human mitochondrial (mtDNA) diversity coalesces to one African female ancestor ("Mitochondrial Eve") some 145 thousand years ago, owing to the ¼ gene pool size of our matrilineally inherited haploid genome. Therefore, most of human prehistory was spent in Africa where early ancestors of Southern African Khoisan and Central African rainforest hunter-gatherers (RFHGs) segregated into smaller groups. Their subdivisions followed climatic oscillations, new modes of subsistence, local adaptations, and cultural-linguistic differences, all prior to their exodus out of Africa. Seven African mtDNA haplogroups (L0-L6) traditionally captured this ancient structure-these L haplogroups have formed the backbone of the mtDNA tree for nearly two decades. Here we describe L7, an eighth haplogroup that we estimate to be ~ 100 thousand years old and which has been previously misclassified in the literature. In addition, L7 has a phylogenetic sublineage L7a*, the oldest singleton branch in the human mtDNA tree (~ 80 thousand years). We found that L7 and its sister group L5 are both low-frequency relics centered around East Africa, but in different populations (L7: Sandawe; L5: Mbuti). Although three small subclades of African foragers hint at the population origins of L5'7, the majority of subclades are divided into Afro-Asiatic and eastern Bantu groups, indicative of more recent admixture. A regular re-estimation of the entire mtDNA haplotype tree is needed to ensure correct cladistic placement of new samples in the future., (© 2022. The Author(s).)

Ventilator-associated pneumonia (VAP) is an infection of the lung parenchyma developing in patients on mechanical ventilation for more than 48 h. VAP is associated with a remarkably constant spectrum of pathogenic bacteria, most of which are aerobic Gram-negative bacilli (AGNB) and, to a lesser extent Staphyloccus aureus. Most authorities agree that VAP develops as a result of aspiration of secretions contaminated with pathogenic organisms, which appear to be endogenously acquired. These pathogens gain access to the distal airways by mechanical reflux and aspiration of contaminated gastric contents and also by repetitive inoculation of contaminated upper airway secretions into the distal tracheobronchial tree. Persistence of these organisms in the upper airways involves their successful colonization of available surfaces. Although exogenous acquisition can occur from the environment, the rapidity at which critically ill patients acquire AGNB in the upper airways in conjunction with the low rate of AGNB colonization of health-care workers exposed to the same environment favors the presence of endogenous proximate sources of AGNB and altered upper airway surfaces that are rendered receptive. Proximate sources of AGNB remain unclear, but potential sites harboring AGNB prior to illness include the upper gastrointestinal tract, subgingival dental plaque, and the periodontal spaces. Following illness or antibiotic therapy, competitive pressures within the oropharynx favor AGNB adherence to epithelial cells, which lead to oropharyngeal colonization. Similar dynamic changes in contiguous structures (oropharynx, trachea, sinuses, and the upper gastrointestinal tract) lead to the transcolonization of these structures with pathogenic bacteria. Following local colonization or infection, these structures serve as reservoirs of AGNB capable of inoculating the lower airways. As the oropharynx becomes colonized with AGNB, contaminated oropharyngeal secretions reach the trachea, endotracheal tube, and ventilator circuit. Contaminated secretions pooled above the endotracheal tube cuff gain access to the trachea and inner lumen of the endotracheal tube by traversing endotracheal tube cuff folds. Amorphic particulate deposits containing AGNB form along the endotracheal tube and are capable of being propelled into the distal airways by ventilator-generated airflow or by tubing manipulation. Bacteria embedded within this type of amorphous matrix are particularly difficult for the host to clear. If host defenses fail to clear the inoculum, then bacterial proliferation occurs, and the host inflammatory response progresses to bronchopneumonia.(ABSTRACT TRUNCATED AT 400 WORDS)

Most patients with adult respiratory distress syndrome (ARDS) survive the initial insult which caused respiratory failure only to succumb later to sepsis caused by nosocomial pneumonia or to pulmonary fibrosis. Clinical criteria and analysis of the tracheal aspirate are notoriously inadequate for establishing a diagnosis of ventilator-associated pneumonia. We implemented a comprehensive diagnostic protocol to determine the cause of sepsis in ARDS patients who had been ventilated for more than three days and who had no bronchoscopic evidence of pneumonia. Nine patients with late ARDS who had fever (89 percent), leukocytosis (89 percent), a new localized infiltrate (78 percent), purulent tracheal secretions (89 percent), low systemic vascular resistance (50 percent), and marked uptake of gallium in the lungs (100 percent) had no source of infection identified. Open-lung biopsy specimens from seven patients showed the fibroproliferative phase of diffuse alveolar damage and confirmed absence of pneumonia. Treatment with prolonged high doses of corticosteroids was associated with a marked and rapid improvement in lung injury score (p less than 0.003 at five days). Our findings indicate that the fibroproliferative process occurring in the lungs of patients with late ARDS gives rise to clinical manifestations identical to those of pneumonia and is potentially responsive to steroid treatment.

Programs of continuing education in mental health are increasing at a rapid pace. This study examines-selected personal and occupational characteristics of enrollees in one such program and classifies the nature of enrollee motivation for participating in specialized programs of community mental health training. The learning-style preferences of these highly experienced professionals are also explored and recommendations are made concering the design of similar educational programs under development elsewhere.