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As bacteria grow and proliferate, they release a variety of volatile compounds that can be profiled and used for speciation, providing an approach amenable to disease diagnosis through quick analysis of clinical cultures as well as patient breath analysis. As a practical alternative to mass spectrometry detection and whole cell pyrolysis approaches, we have developed methodology that involves detection via a sensitive, micromachined differential mobility spectrometer (microDMx), for sampling head-space gases produced by bacteria growing in liquid culture. We have applied pattern discovery/recognition algorithms (ProteomeQuest) to analyze headspace gas spectra generated by microDMx to reliably discern multiple species of bacteria in vitro: Escherichia coli, Bacillus subtilis, Bacillus thuringiensis, and Mycobacterium smegmatis. The overall accuracy for identifying volatile profiles of a species within the 95% confidence interval for the two highest accuracy models evolved was between 70.4 and 89.3% based upon the coordinated expression of between 5 and 11 features. These encouraging in vitro results suggest that the microDMx technology, coupled with bioinformatics data analysis, has potential for diagnosis of bacterial infections.

The ongoing Zika virus epidemic in the Americas and the observed association with both fetal abnormalities (primary microcephaly) and adult autoimmune pathology (Guillain–Barré syndrome) has brought attention to this neglected pathogen. While initial case studies generated significant interest in the Zika virus outbreak, larger prospective epidemiology and basic virology studies examining the mechanisms of Zika viral infection and associated pathophysiology are only now starting to be published. In this review, we analyze Zika fetal neuropathogenesis from a comparative pathology perspective, using the historic metaphor of “TORCH” viral pathogenesis to provide context. By drawing parallels to other viral infections of the fetus, we identify common themes and mechanisms that may illuminate the observed pathology. The existing data on the susceptibility of various cells to both Zika and other flavivirus infections are summarized. Finally, we highlight relevant aspects of the known molecular mechanisms of flavivirus replication. [ABSTRACT FROM AUTHOR]

Introduction: Reports of high rates of primary microcephaly and Guillain–Barré syndrome associated with Zika virus infection in French Polynesia and Brazil have raised concerns that the virus circulating in these regions is a rapidly developing neuropathic, teratogenic, emerging infectious public health threat. There are no licensed medical countermeasures (vaccines, therapies or preventive drugs) available for Zika virus infection and disease. The Pan American Health Organization (PAHO) predicts that Zika virus will continue to spread and eventually reach all countries and territories in the Americas with endemic Aedes mosquitoes. This paper reviews the status of the Zika virus outbreak, including medical countermeasure options, with a focus on how the epidemiology, insect vectors, neuropathology, virology and immunology inform options and strategies available for medical countermeasure development and deployment. Methods: Multiple information sources were employed to support the review. These included publically available literature, patents, official communications, English and Lusophone lay press. Online surveys were distributed to physicians in the US, Mexico and Argentina and responses analyzed. Computational epitope analysis as well as infectious disease outbreak modeling and forecasting were implemented. Field observations in Brazil were compiled and interviews conducted with public health officials. [ABSTRACT FROM AUTHOR]

Iminosugars that are competitive inhibitors of endoplasmic reticulum (ER) -glucosidases have been demonstrated to have antiviral activity against a diverse set of viruses. A novel iminosugar, UV-4B, has recently been shown to provide protection against lethal infections with dengue and influenza A (H1N1) viruses in mice. In the current study, the breadth of activity of UV-4B against influenza was examined ex vivo and in vivo. Efficacy of UV-4B against influenza A and B viruses was shown in primary human bronchial epithelial cells, a principal target tissue for influenza. Efficacy of UV-4B against influenza A (H1N1 and H3N2 subtypes) and influenza B was demonstrated using multiple lethal mouse models with readouts including mortality and weight loss. Clinical trials are ongoing to demonstrate safety of UV-4B and future studies to evaluate antiviral activity against influenza in humans are planned. [ABSTRACT FROM AUTHOR]

Background: Bats are reservoirs for a diverse range of coronaviruses (CoVs), including those closely related to human pathogens such as Severe Acute Respiratory Syndrome (SARS) CoV and Middle East Respiratory Syndrome CoV. There are approximately 139 bat species reported to date in Thailand, of which two are endemic species. Due to the zoonotic potential of CoVs, standardized surveillance efforts to characterize viral diversity in wildlife are imperative. Findings: A total of 626 bats from 19 different bat species were individually sampled from 5 provinces in Eastern Thailand between 2008 and 2013 (84 fecal and 542 rectal swabs). Samples collected (either fresh feces or rectal swabs) were placed directly into RNA stabilization reagent, transported on ice within 24 hours and preserved at -80°C until further analysis. CoV RNA was detected in 47 specimens (7.6%), from 13 different bat species, using broadly reactive consensus PCR primers targeting the RNA-Dependent RNA Polymerase gene designed to detect all CoVs. Thirty seven alphacoronaviruses, nine lineage D betacoronaviruses, and one lineage B betacoronavirus (SARS-CoV related) were identified. Six new bat CoV reservoirs were identified in our study, namely Cynopterus sphinx, Taphozous melanopogon, Hipposideros lekaguli, Rhinolophus shameli, Scotophilus heathii and Megaderma lyra. Conclusions: CoVs from the same genetic lineage were found in different bat species roosting in similar or different locations. These data suggest that bat CoV lineages are not strictly concordant with their hosts. Our phylogenetic data indicates high diversity and a complex ecology of CoVs in bats sampled from specific areas in eastern regions of Thailand. Further characterization of additional CoV genes may be useful to better describe the CoV divergence. [ABSTRACT FROM AUTHOR]

Background: To evaluate the current status of malaria at parturition and its impact on delivery outcome in Nigeria.Methods: A total of 2500 mother-neonate pairs were enrolled at 4 sites over a 12-month period. Maternal and placental blood smears for malaria parasitaemia and haematocrit were determined.Results: Of the 2500 subjects enrolled, 625 were excluded from analysis because of breach in study protocol. The mean age of the remaining 1875 mothers was 29.0 +/- 5.1 years. The prevalence of parasitaemia was 17% and 14% in the peripheral blood and placenta of the parturient women, respectively. Peripheral blood parasitaemia was negatively associated with increasing parity (P < .0001). Maternal age <20 years was significantly associated with both peripheral blood and placental parasitaemia. After adjusting for covariates only age <20 years was associated with placental parasitaemia. Peripheral blood parasitaemia in the women was associated with anaemia (PCV < or =30%) lower mean hematocrit (P < .0001). lower mean birth weight (P < .001) and a higher proportion of low birth weight babies (LBW), (P = .025).Conclusion: In Nigeria, maternal age < 20 years was the most important predisposing factor to malaria at parturition. The main impacts on pregnancy outcome were a twofold increase in rate of maternal anaemia and higher prevalence of LBW. [ABSTRACT FROM AUTHOR]

Since congenital malaria had previously been thought to be rare, blood film examination for malaria parasites is still sometimes not routinely performed in ill neonates in malaria-endemic regions. Because of increasing published reports of congenital malaria in Nigeria, there is a need to characterize the clinical and laboratory manifestations associated with malaria parasitemia within the first few hours of life. In a 12-month (April 2003-March 2004), multicenter study in Nigeria, thin and thick blood smears made from maternal (finger prick), placental aspirates, cord blood and neonate (heel prick taken within 4 hours of life) were Giemsa-stained and examined by light microscopy for asexual stages of Plasmodium. Parasitemic neonates were closely monitored for clinical and laboratory features of symptomatic malaria. Plasmodium falciparum was found in 5.1% (95/1875) of neonatal heel pricks; mean parasite density was low (mean = 48/μL, range 8–200/μL). Antepartum maternal and placental parasitemia were the most important risk factors for congenital parasitemia (P < 0.001 and P < 0.001). Prolonged labor and prolonged rupture of membranes were also significant factors in the symptomatic neonates. Sixty-one percent (58/95) of parasitemic babies were asymptomatic, while 38.9% (37/95) of them exhibited signs of possible infection. The presence of any symptom was significantly related to parasitemia (P < 0.001). Among the symptomatic parasitemic babies the most common symptoms were, fever (temperature >37.5&degic;) within the first 24 hours of life (100%) and refusal to suck (10.8%). Anemia at birth (hematocrit <42%) was found in 15.7% (15/95) of parasitemic babies as compared to 9.2% in the non-parasitemic ones. (P = 0.03, OR = 1.84). The mean hematocrit of parasitemic neonates within 4 hours of life was 49.5 ± 6.4 as compared to 52.6 ± 8.2 in non-parasitemic babies (P = 0.001). Furthermore, the mean hematocrit was 44.0 ± 5.5% in the symptomatic parasitemic babies. All symptomatic babies were treated with oral chloroquine with a cure rate of 89.1%. Treatment failures subsequently received oral sulfadoxine-pyrimethamine with good outcome. The febrile newborn should be evaluated for malaria especially if there is a history of prolonged labor or in the presence of maternal malaria infection. Efforts should be intensified to reduce the burden of maternal, placental malaria and therefore congenital malaria. [ABSTRACT FROM AUTHOR]

Blockade of immune-checkpoint programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 can enhance effector T-cell responses. However, the lack of response in many patients to checkpoint-inhibitor therapies emphasizes the need for combination immunotherapies to pursue maximal antitumor efficacy. We have previously demonstrated that antagonism of C-X-C chemokine receptor type 4 (CXCR4) by plerixafor (AMD3100) can decrease regulatory T (T reg )-cell intratumoral infiltration. Therefore, a combination of these 2 therapies might increase antitumor effects. Here, we evaluated the antitumor efficacy of AMD3100 and anti-PD-1 (αPD-1) antibody alone or in combination in an immunocompetent syngeneic mouse model of ovarian cancer. We found that AMD3100, a highly specific CXCR4 antagonist, directly down-regulated the expression of both C-X-C motif chemokine 12 (CXCL12) and CXCR4 in vitro and in vivo in tumor cells. AMD3100 and αPD-1 significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice when given as monotherapy. Combination of these 2 agents significantly enhanced antitumor effects compared with single-agent administration. Benefits of tumor control and animal survival were associated with immunomodulation mediated by these 2 agents, which were characterized by increased effector T-cell infiltration, increased effector T-cell function, and increased memory T cells in tumor microenvironment. Intratumoral T reg cells were decreased, and conversion of T reg cells into T helper cells was increased by AMD3100 treatment. Intratumoral myeloid-derived suppressor cells were decreased by the combined treatment, which was associated with decreased IL-10 and IL-6 in the ascites. Also, the combination therapy decreased suppressive leukocytes and facilitated M2-to-M1 macrophage polarization in the tumor. These results suggest that AMD3100 could be used to target the CXCR4-CXCL12 axis to inhibit tumor growth and prevent multifaceted immunosuppression alone or in combination with αPD-1 in ovarian cancer, which could be clinically relevant to patients with this disease.-Zeng, Y., Li, B., Liang, Y., Reeves, P. M., Qu, X., Ran, C., Liu, Q., Callahan, M. V., Sluder, A. E., Gelfand, J. A., Chen, H., Poznansky, M. C. Dual blockade of CXCL12-CXCR4 and PD-1-PD-L1 pathways prolongs survival of ovarian tumor-bearing mice by prevention of immunosuppression in the tumor microenvironment.

Disasters, natural and man-made, have a considerable impact on communities. Most recently, disasters stemming from terrorist attacks have become a leading cause of concern. The importance of work in the lives of employees, coupled with the vulnerability of workplaces as potential targets of terrorist attacks, suggests that workplaces can and should play a role in planning for, and responding to, disasters. This article addresses the role of the workplace in disasters, with an emphasis on the psychological impact of such events, by drawing upon experience and literature related to workplace violence and to other traumatic events in the workplace.

Interleukin-1 (also known as osteoclast activating factor, OAF) is a cytokine produced primarily by monocytes and macrophages and is thought to mediate many of the immunologic, metabolic, and endocrine alterations seen with microbial infection, tissue injury, inflammatory disease, and bone loss. Stimuli for IL-1 production include microorganisms, endotoxins (LPS), antigen-antibody complexes, clotting components, and other cytokines. The purpose of this study was to determine whether dental implants stimulated peripheral blood mononuclear cells (PBMCs) to produce IL-1β (OAF) as well as tumor necrosis factor (TNFα). This production may lead to bone loss or failure of an implant. Three duplicates of five different implants were incubated with 2 × 106 PBMCs/ ml in 20% autologous serum; the esterase positive PBMCs amounted to 14.5%. Measured by radioimmunoassay techniques and compared to controls, all of the implants except one caused significant in vitro generation of IL-1β and TNFα. The stimulation of IL1β/TNFα production by these materials suggests that they are not physiologically inert and that the IL-1β (OAF) production may contribute to a less favorable osseoadaptation. OAF has a physiologic (homeostatic) role in maintenance and alteration of osseous structures, but the level at which physiologic becomes pathologic is unknown. Although there were statistical differences between the cellular response to these implants, the clinical significance of the differences remains to be determined. J Periodontol 1992; 63:426-430., (© 1992 American Academy of Periodontology.)