Neonatal sepsis is a significant health issue associated with high mortality. Immune responses associated with neonatal sepsis, such as proinflammatory cytokine production, are believed to play a central role in the pathogenesis of this disease. In the present study, serum levels of the proinflammatory cytokines TNF-α, IL1-β, and IL-6 and the anti-inflammatory cytokines IL-4 and IL-10 were evaluated for 25 subjects with neonatal sepsis. We observed that subjects with late onset of sepsis (LOS), as well as those with early onset of sepsis (EOS), had a substantial increase in serum TNF-α. In contrast to EOS, subjects with LOS demonstrated a significant increase in serum levels IL-6 and IL-10. Additionally, we observed a significant difference in cytokine profiles between acute and postacute cases of neonatal sepsis. For instance, the level of proinflammatory cytokines, such as TNF-α and IL-6, was elevated in the acute phase, whereas the production of anti-inflammatory cytokines, such as IL-10, became substantially upregulated during the postacute phase. Additionally, no correlation was observed between cytokine levels and CRP levels or lymphocyte counts. Thus, in contrast to CRP levels and lymphocyte counts, examination of the cytokine profile can provide valuable information when determining the most effective therapy for treating neonatal sepsis. This information may be useful to physicians when determining if anti-inflammatory or immune stimulatory therapy is warranted.

Nephropathia epidemica (NE) is a form of hemorrhagic fever with renal syndrome associated with the Puumala virus species of Hantavirus. The pathogenesis of NE is not well understood; therefore, investigating the inflammatory cytokine response to infection may provide useful knowledge in deciphering the pathophysiology of NE. Using Luminex and ELISA, we analyzed the serum of 137 NE cases and 44 controls to investigate if serum cytokines associate with different clinical presentations. Serum levels of TNF-α and IL-1β are associated with disease severity while upregulation of IL-6, CXCL10, CCL2 and CCL3 are associated with clinical presentation. Inflammatory cytokine kinetics associate with the severity and phase of NE. Our data support a role for inflammatory cytokines in the pathophysiology of NE.

Background: Russia has a substantial HIV epidemic which is poised to escalate in the coming years. The increases in prevalence of HIV will result in increased healthcare needs by a medical system with limited experience with HIV. A healthcare provider's attitude towards a patient plays a significant role in determining the patient's health‐related behaviours and medical outcomes. Previous studies have identified negative attitudes of medical students towards people living with HIV. Studying the prevalence of such attitudes is of particular interest, as medical students represent the future workforce and also as the schooling years present a unique opportunity to nurture bias‐free healthcare providers. The study measures prevalence of prejudicial attitudes towards HIV‐positive and HIV‐negative patients who belong to marginalized subgroups.Methods: The cross‐sectional survey was conducted among medical students of a Russian medical university. Of 500 students surveyed, 436 provided sufficient data to be included in the analysis. Prejudicial attitudes were defined as reluctance to provide medical care to a specified hypothetical patient. Nine hypothetical HIV‐positive and HIV‐negative patients were proposed: physicians, injecting drug users, commercial sex workers, men who have sex with men and a patient HIV‐positive due to blood transfusion. A log‐binomial regression solved using generalized estimating equations was utilized to identify factors associated with reluctance to treat.Results: Prevalence of reluctance to provide medical care to HIV‐positive patients in marginalized subgroups was high (ranging from 26.4% up to 71.9%), compared to a maximum of 7.5% if a patient was an HIV‐negative physician. Students in their clinical years reported more negative attitudes than preclinical students. In general, female students were less willing to provide care than their male counterparts.Conclusions: Prejudicial attitudes about HIV‐positive patients and those in marginalized subgroups of the population are prevalent among medical students in Russia. Given the increasing prevalence of HIV in the country, reasons for this hesitance to treat must be identified and addressed. Educational programs for healthcare providers are urgently needed to eliminate bias in the delivery of critically needed medical care. These targeted interventions should be coupled with other programs to eliminate structural barriers to care.

The genetic background of an individual plays an important role in the progression of HIV infection to AIDS. Identifying previously unknown or uncharacterized single nucleotide polymorphisms (SNPs) that associate with disease progression may reveal important therapeutic targets and provide a greater understanding of disease pathogenesis. In the present study, we employed ultra-high multiplex PCR on an Ion Torrent next-generation sequencing platform to sequence 23 innate immune genes from 94 individuals with HIV/AIDS. This data was used to identify potential associations of SNPs with clinical parameters and disease progression. SNPs that associated with an increased viral load were identified in the genes for the interleukin 15 receptor (IL15RA), toll-like receptor 7 (TLR7), tripartite motif-containing protein 5 (TRIM5), and two killer-cell immunoglobulin-like receptors (KIR2DL1andKIR2DL3). Additionally, SNPs that associated with progression from HIV infection to AIDS were identified in two 2′-5′-oligoadenylate synthetase genes (OAS2andOAS3). In contrast, other SNPs identified inOAS2andOAS3genes, as well as in theTRIM5andKIR2DS4genes, were associated with a slower progression of disease. Taken together, our data demonstrates the utility of ultra-high multiplex PCR in identifying polymorphisms of potential clinical significance and further,identifies SNPs that may play a role in HIV pathogenesis.

Plasmacytoid dendritic cells in the periphery of subjects with HIV/AIDS decrease over time and the fate of these cells has been the subject of ongoing investigation. Previous studies using animal models as well as studies with humans suggest that these cells may redistribute to the gut. Other studies using animal models propose that the periphery pDCs are depleted and gut is repopulated with naïve pDCs from the bone marrow. In the present study, we utilized immunohistochemistry to survey duodenum biopsies of subjects with HIV/AIDS and controls. We observed that subjects with HIV/AIDS had increased infiltration of Ki-67+/CD303+ pDCs, a phenotype consistent with bone marrow derived pre-pDCs. In contrast, Ki-67+/CD303+ pDCs were not observed in control biopsies. We additionally observed that gut-associated pDCs in HIV/AIDS cases upregulate the proapototic enzyme granzyme B; however, no granzyme B was observed in the pDCs of control biopsies. Our data are consistent with reports in animal models that suggest periphery pDCs are depleted by exhaustion and that naïve pDCs egress from the bone marrow and ultimately infiltrate the gut mucosa. Additionally, our observation of granzyme B upregulation in naïve pDCs may identify a contributing factor to the gut pathology associated with HIV infection.

Kidney insufficiency is a hallmark of nephropathia epidemica (NE). Little is known about the mechanisms of the NE kidney pathology, with current knowledge mainly based on findings in postmortem tissue. We have analyzed kidney damage biomarkers in urine collected from early- and late-phase NE using Bio-Plex kidney toxicity panels 1 and 2. To determine the disease specificity, kidney damage biomarkers were also analyzed in urine samples from patients diagnosed with gout, type 2 diabetes, systemic lupus erythematosus, and chronic kidney insufficiency. Analysis of 12 biomarkers suggests damage to the kidney proximal tubule at the onset of NE. Also, upregulation of biomarkers of inflammation and leukocyte chemotaxis were detected in NE urine. Furthermore, increased clusterin levels were found in early- and late-phase NE urine. Comparative analysis revealed that clusterin is a biomarker, upregulated in NE urine.