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Background: The cell cycle is a critical mechanism for proper cellular growth, development and viability. The p16INK4a and p21Waf1/Cip1are important regulators of the cell cycle progression in response to internal and external stimuli (e.g. stress). Accumulating evidence indicates that the prefrontal cortex (PFC) is particularly vulnerable to stress, where stress induces, among others, molecular and morphological alterations, reflecting behavioral changes. Here, we investigated if the p16INK4a and p21Waf1/Cip1 expression are associated with behavioral outcomes. Methods: PFC mRNA and protein levels of p16INK4A and p21Waf1/Cip1 of mice (6 independent groups of C57BL/6J, 8 mice/group, 50% female) exposed from 0 to 35 days of chronic restraint stress (CRS) were quantified by qPCR and Western Blot, respectively. Correlation analyses were used to investigate the associations between CKIs expression and anxiety- and depression-like behaviors. Results: Our results showed that the prefrontal cortex activated the cell cycle regulation pathways mediated by both CKIs p16INK4A and p21Waf1/Cip1 in mice exposed to CRS, with overall decreased mRNA expression and increased protein expression. Moreover, correlation analysis revealed that mRNA and protein levels are statistically significant correlated with anxiety and depressive-like behavior showing a greater effect in males than females. Conclusions: Our present study extends the existing literature providing evidence that prefrontal cortex cells respond to chronic stress exposure by overexpressing CKIs. Furthermore, our findings indicated that abnormal expression of p16INK4A and p21Waf1/Cip1 may significantly contribute to non-adaptive behavioral responses.

We report two outbreaks of Lassa fever that occurred in Benin in 2014 and 2016 with 20 confirmed cases and 50% (10/20) mortality. Benin was not previously considered to be an endemic country for Lassa fever, resulting in a delay to diagnose the disease and its human transmission. Molecular investigations showed the viral genomes to be similar to that of the Togo strain, which is genetically very different from other known strains and confirms the existence of a new lineage. Endemic circulation of Lassa virus in a new territory and the genetic diversity thus confirm that this virus represents a growing threat for West African people. Given the divergence of the Benin strain from the prototypic Josiah Sierra Leone strain frequently used to generate vaccine candidates, the efficacy of vaccine candidates should also be demonstrated with this strain.

Background. Staphylococcus aureus superantigens are associated with the pathogenesis of toxic shock syndrome, but their involvement in septic shock is unknown. Methods. We compared the distribution of 11 superantigen genes in S. aureus blood culture isolates obtained from patients with sepsis who did and did not have septic shock (19 and 61 patients, respectively), as well as from patients with suppurative infections (101 patients) and patients with colonization (25 patients). Results. The prevalence of the enterotoxin A gene (sea) increased significantly with the severity of infection (P < .001), whereas the prevalence of the enterotoxin gene cluster (egc) decreased significantly (P = .009). Conclusion. Enterotoxin A (SEA) might play a key role in sea-positive S. aureus sepsis by triggering over-expression of inflammatory mediators associated with shock. Novel treatments targeting superantigens, especially the sea gene, might be beneficial in the treatment of S. aureus sepsis.

Sudan ebolavirus (SUDV) is one of four members of the Ebolavirus genus known to cause Ebola Virus Disease (EVD) in humans, which is characterized by hemorrhagic fever and a high case fatality rate. While licensed therapeutics and vaccines are available in limited number to treat infections of Zaire ebolavirus, there are currently no effective licensed vaccines or therapeutics for SUDV. A well-characterized animal model of this disease is needed for the further development and testing of vaccines and therapeutics. In this study, twelve cynomolgus macaques (Macaca fascicularis) were challenged intramuscularly with 1000 PFUs of SUDV and were followed under continuous telemetric surveillance. Clinical observations, body weights, temperature, viremia, hematology, clinical chemistry, and coagulation were analyzed at timepoints throughout the study. Death from SUDV disease occurred between five and ten days after challenge at the point that each animal met the criteria for euthanasia. All animals were observed to exhibit clinical signs and lesions similar to those observed in human cases which included: viremia, fever, dehydration, reduced physical activity, macular skin rash, systemic inflammation, coagulopathy, lymphoid depletion, renal tubular necrosis, hepatocellular degeneration and necrosis. The results from this study will facilitate the future preclinical development and evaluation of vaccines and therapeutics for SUDV.

Antibiotic-resistance of hospital-acquired infections is a major public health issue. The worldwide emergence and diffusion of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, including Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP), is of particular concern. Preventing their nosocomial spread requires understanding their transmission. Using Close Proximity Interactions (CPIs), measured by wearable sensors, and weekly ESBL-EC-and ESBL-KP-carriage data, we traced their possible transmission paths among 329 patients in a 200-bed long-term care facility over 4 months. Based on phenotypically defined resistance profiles to 12 antibiotics only, new bacterial acquisitions were tracked. Extending a previously proposed statistical method, the CPI network's ability to support observed incident-colonization episodes of ESBL-EC and ESBL-KP was tested. Finally, mathematical modeling based on our findings assessed the effect of several infection-control measures. A potential infector was identified in the CPI network for 80% (16/20) of ESBL-KP acquisition episodes. The lengths of CPI paths between ESBL-KP incident cases and their potential infectors were shorter than predicted by chance (P = 0.02), indicating that CPI-network relationships were consistent with dissemination. Potential ESBL-EC infectors were identified for 54% (19/35) of the acquisitions, with longer-than-expected lengths of CPI paths. These contrasting results yielded differing impacts of infection control scenarios, with contact reduction interventions proving less effective for ESBL-EC than for ESBL-KP. These results highlight the widely variable transmission patterns among ESBL-producing Enterobacteriaceae species. CPI networks supported ESBL-KP, but not ESBL-EC spread. These outcomes could help design more specific surveillance and control strategies to prevent in-hospital Enterobacteriaceae dissemination.

To probe encephalopathy pathogenesis during toxic shock syndrome (TSS), we investigated the fate of bloodborne TSS toxin–1 (TSST-1) as it moves through the choroid plexus epithelium that forms the main blood–cerebrospinal fluid (CSF) barrier and the effect that TSST-1 has on choroidal barrier properties and on cultured neuronal cell viability. TSST-1 showed a slow, diffusional movement across a cellular model of the blood-CSF barrier but did not compromise the integrity of the barrier. Relevant to the acute symptoms of TSS, a combination of human leukocytes and the toxin induced a decrease in CSF clearance of the pyrogenic prostaglandin E2 (PGE2). The direct effects that TSST-1 had on primary cortical neuron cultures and a neuronal cell line involved elevated caspase 3/7 levels, which correlated with an increase in neuronal cell death. The results of the present study suggest that TSST-1 can affect the brain, by inducing both an intracerebral increase in PGE2 concentration and caspase-dependent neuronal death, which are possibly relevant to long-term intoxication

Understanding transmission routes of hospital-acquired infections (HAI) is key to improve their control. In this context, describing and analyzing dynamic inter-individual contact patterns in hospitals is essential. In this study, we used wearable sensors to detect Close Proximity Interactions (CPIs) among patients and hospital staff in a 200-bed long-term care facility over 4 months. First, the dynamic CPI data was described in terms of contact frequency and duration per individual status or activity and per ward. Second, we investigated the individual factors associated with high contact frequency or duration using generalized linear mixed-effect models to account for inter-ward heterogeneity. Hospital porters and physicians had the highest daily number of distinct contacts, making them more likely to disseminate HAI among individuals. Conversely, contact duration was highest between patients, with potential implications in terms of HAI acquisition risk. Contact patterns differed among hospital wards, reflecting varying care patterns depending on reason for hospitalization, with more frequent contacts in neurologic wards and fewer, longer contacts in geriatric wards. This study is the first to report proximity-sensing data informing on inter-individual contacts in long-term care settings. Our results should help better understand HAI spread, parameterize future mathematical models, and propose efficient control strategies.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Walter Scott's exciting tale of chivalry, daring-do and intrigue set in the Holy Land at the time of the Crusades. A brave Scottish knight foils Richard the Lionheart's assassins, winning the gratitude of the king and the hand of the lady he loves.

Walter Scott's exciting tale of chivalry, daring-do and intrigue set in the Holy Land at the time of the Crusades. A brave Scottish knight foils Richard the Lionheart's assassins, winning the gratitude of the king and the hand of the lady he loves.