High soluble CD163 levels correlate with disease progression and inflammation in Kenyan children with perinatal HIV-infection

Objectives: CD163 is a hemoglobin scavenger receptor on monocytes and macrophages, cleaved to soluble CD163 (sCD163) in the plasma following activation. In HIV+ adults, sCD163 is linked to non-AIDS morbidity and predicts mortality, but there is limited data in children. We investigated sCD163 levels in HIV+ children and their correlations with disease progression, immune activation and gut mucosal damage. Design and methods: We quantified sCD163 levels in Kenyan children aged 0–20 years with perinatal HIV infection, including 74 antiretroviral treatment (ART)-naïve (ART−) and 64 virally suppressed on ART (ART+), and 79 HIV unexposed-uninfected controls (HIV−). The cohort was divided into age groups 0–5 (younger) and 5–20 (older) years. Correlations between sCD163 and HIV viral load, %CD8+, CD4+ : CD8+ ratio, markers of T-cell activation and proliferation, and gut mucosal damage were also assessed. Results: ART− children have higher sCD163 levels compared with HIV− and ART+ children (P ≤ 0.01); ART+ have equivalent sCD163 levels to HIV− children. In a prospective analysis, sCD163 levels decreased in older ART− children after 12 months of treatment (P < 0.0001). Regardless of age, sCD163 levels correlate with clinical disease progression measured by %CD4+ T cells, CD4+ : CD8+ T-cell ratios and HIV viral load. sCD163 levels directly correlate with T-cell activation markers CD38, human leukocyte antigen-DR isotype, and Ki67 (P ≤ 0.01). Conclusion: High plasma sCD163 levels in HIV+ children correlate with advancing disease and T-cell activation. ART initiation normalizes sCD163 levels and may alleviate HIV-related morbidities and improve long-term pediatric outcomes

Low Peripheral T Follicular Helper Cells in Perinatally HIV-Infected Children Correlate With Advancing HIV Disease.

Background: T follicular helper (Tfh) cells are crucial for B cell differentiation and antigen-specific antibody production. Dysregulation of Tfh-mediated B cell help weakens B cell responses in HIV infection. Moreover, Tfh cells in the lymph node and peripheral blood comprise a significant portion of the latent HIV reservoir. There is limited data on the effects of perinatal HIV infection on Tfh cells in children. We examined peripheral Tfh (pTfh) cell frequencies and phenotype in HIV-infected children and their associations with disease progression, immune activation, and B cell differentiation. Methods: In a Kenyan cohort of 76 perinatally HIV-infected children, comprised of 43 treatment-naïve (ART-) and 33 on antiretroviral therapy (ART+), and 42 healthy controls (HIV-), we identified memory pTfh cells, T cell activation markers, and B cell differentiation states using multi-parameter flow cytometry. Soluble CD163 and intestinal fatty acid-binding protein plasma levels were quantified by ELISA. Results: ART- children had reduced levels of pTfh cells compared with HIV- children that increased with antiretroviral therapy. HIV+ children had higher programmed cell death protein 1 (PD-1) expression on pTfh cells, regardless of treatment status. Low memory pTfh cells with elevated PD-1 levels correlated with advancing HIV disease status, indicated by increasing HIV viral loads and T cell and monocyte activation, and decreasing %CD4 and CD4:CD8 ratios. Antiretroviral treatment, particularly when started at younger ages, restored pTfh cell frequency and eliminated correlations with disease progression, but failed to lower PD-1 levels on pTfh cells and their associations with CD4 T cell percentages and activation. Altered B cell subsets, with decreased naïve and resting memory B cells and increased activated and tissue-like memory B cells in HIV+ children, correlated with low memory pTfh cell frequencies. Last, HIV+ children had decreased proportions of CXCR5+ CD8 T cells that associated with low %CD4 and CD4:CD8 ratios. Conclusion: Low memory pTfh cell frequencies with high PD-1 expression in HIV+ children correlate with worsening disease status and an activated and differentiated B cell profile. This perturbed memory pTfh cell population may contribute to weak vaccine and HIV-specific antibody responses in HIV+ children. Restoring Tfh cell capacity may be important for novel pediatric HIV cure and vaccine strategies

Determining the Protein-Protein Interactions Within the Bacterial mRNA Degradosome and the Regulators of RpoS Under Nitrogen Limiting Conditions

Bacteria encounter a range of conditions throughout their lives and must be able to defend themselves against stressful environments. For Escherichia coli, α factors are integral to this adaptation process. These factors and their regulators are therefore prime targets for more specific antibacterial therapies. Some of the α factors are induced under a specific stress to bind RNA polymerase in order to upregulate the genes required to combat the particular stress encountered. RpoS is one such sigma factor and is indispensable for E. coli 's survivial . Integral in facilitating RpoS function are the anti-adaptor proteins IraP, IraM and IraD, and the sRNA's DsrA and RprA, which upregulate RpoS during different stress conditions. In this study we demonstrate that IraP and the sRNA DsrA post-translationally and translationally upregulate RpoS, respectively, during nitrogen-limited conditions. Additionally, we demonstrate that AppY, previously considered only to be a transcriptional activator, possibly interacts directly with SprE as an anti-adaptor to post-translationally upregulate RpoS. Interestingly, SprE has a second function independent of its effects on RpoS levels, which is to assist in mRNA degradation. Although the components responsible for mRNA degradation have largely been discovered and their general functions teased apart, SprE's role in the mRNA degradosome pathway remains unknown. Here we demonstrate via bacterial two-hybrid analysis that SprE possibly interacts directly with the core degradosome component PNPase and transiently, or indirectly with PAPI

Baseline differences in characteristics and risk behaviors among people who inject drugs by syringe exchange program modality: an analysis of the Miami IDEA syringe exchange

Abstract Background In March of 2016, Florida passed the Infection Disease Elimination Act (IDEA), legalizing the formation of the first syringe exchange program in Florida, which opened in December of 2016 at a fixed site in Overtown, Miami. Since that time, the exchange expanded in April of 2017 to include a mobile van unit that provides the same services at different locations throughout Miami-Dade County. Methods Trained interviewers conducted face-to-face interviews from all first-time participants at the IDEA Exchange, both at the fixed site and the mobile van unit. Results Among 718 first-time enrollees, 74.8% were male, 52.1% were non-Hispanic White, 85.9% completed high school, 59.8% were unemployed, 42.1% were homeless, 54.2% reported an annual income of less than $15,000, and the mean age was 38 years. Participants at the fixed site and mobile van unit reported differences in socioeconomic status, injection drug-related behaviors, and pre-existing hepatitis C virus (HCV) infection status. Conclusions Taken together, these results suggest that the mobile unit is capturing a subset of PWID in Miami that the fixed site is not, and vice-versa. As the opioid crisis extends into all demographics, such multimodal efforts to target various populations of PWID should be kept in mind, especially when unveiling future syringe exchanges in Florida and other late-adopting states

Thirty-day readmissions following parathyroidectomy: Evidence from the National Readmissions Database, 2013-2014

Parathyroidectomy is one of the most common procedures performed in the United States, and are increasingly being performed safely in the outpatient setting. However, complications from surgery can be life-threatening, and thus an understanding of who may be at risk is essential. We analyzed and compared the risk factors for patients readmitted within 30 days following inpatient parathyroidectomy for primary or secondary hyperparathyroidism. We reviewed the National Readmissions Database from 2013 to 2014 for patients who received inpatient parathyroidectomy for primary or secondary hyperparathyroidism. The primary outcome was non-elective readmission within 30 days. Multivariate logistic regression was used to analyze risk factor odds ratios for readmission. 7171 patients underwent inpatient parathyroidectomies in 2013 and 2014. 59.89% of parathyroidectomies were performed for primary hyperparathyroidism, with a 5.6% readmission rate. Most common causes of readmission were septicemia (13.69%), hypocalcemia (12.86%), heart failure (10.79%) and renal failure (9.54%). Having Medicare (OR: 1.71, CI:1.14-2.59, p = .01), Medicaid (OR: 3.24, CI: 2.03-5.17, p < .001), and self-paying (OR: 2.43, CI: 1.11-5.32, p = .02), were associated with increased odds of readmission for those with primary hyperparathyroidism. 21.99% of parathyroidectomies were performed for secondary hyperparathyroidism, with a 19.4% readmission rate. Most common causes of readmission were hypocalcemia (22.88%), hungry bone syndrome (14.38%), electrolyte disorders (13.73%), and renal failure (11.11%). Patients with secondary hyperparathyroidism are older, poorer and have more comorbidities than patients with primary hyperparathyroidism, and are more likely to be readmitted within 30 days of parathyroidectomy

Association of UV radiation with Parkinson disease incidence: A nationwide French ecologic study

International audienceBackground: Vitamin D is thought to contribute to brain health, but it is unclear whether low vitamin D levels are associated with increased incidence of Parkinson's disease (PD). Using ultraviolet B (UV-B) as a surrogate for vitamin D levels, we conducted a nationwide ecologic study in France in order to examine the association of UV-B with PD incidence. Methods: We used French national drug claims databases to identify PD cases using a validated algorithm. UV-B data from the solar radiation database were derived from satellite images. We estimated PD incidence (2010– 2012) at the canton level (small administrative French unit) and used multilevel Poisson regression to examine its association with UV-B (2005 annual average), after adjustment for age, sex, deprivation index, density of neurologists, smoking, proportion of agricultural land, and vitamin D supplementation. Results: Analyses are based on 69,010 incident PD patients. The association between UV-B and PD incidence was quadratic (P < 0.001) and modified by age (P < 0.001). Below 70y, incidence was higher in the bottom quintile (relative risk, RR Q1:45-49y =1.18, 95% CI=1.08–1.29) compared with the middle UV-B quintile, and lower in the top quintile (RR Q5:45-49y =0.85 [0.77–0.94]). An opposite pattern was observed in older subjects (RR Q1:85-89y =0.92 [0.89–0.96]; RR Q5:85-89y =1.06 [1.02–1.11]). Analysis based on continuous UV-B yielded similar conclusions. Conclusions: In this nationwide study, there was an age-dependent quadratic association between UV-B and PD incidence. This study suggests that reasonable UV-B exposure is associated with lower PD risk in younger persons and that future studies should examine dose-response relations and take age into account

FOXP3+Helios+ Regulatory T Cells, Immune Activation, and Advancing Disease in HIV-Infected Children.

Regulatory T cells (Tregs) are functionally suppressive CD4 T cells, critical for establishing peripheral tolerance and controlling inflammatory responses. Previous reports of Tregs during chronic HIV disease have conflicting results with higher or lower levels compared with controls. Identifying true Tregs with suppressive activity proves challenging during HIV infection, as traditional Treg markers, CD25 and FOXP3, may transiently upregulate expression as a result of immune activation (IA). Helios is an Ikaros family transcription factor that marks natural Tregs with suppressive activity and does not upregulate expression after activation. Coexpression of FOXP3 and Helios has been suggested as a highly specific marker of bona fide Tregs. We evaluated Treg subsets by FOXP3 coexpressed with either CD25 or Helios and their association with HIV disease progression in perinatally infected HIV-positive children. Identifying Tregs by FOXP3 coexpression with Helios rather than CD25 revealed markedly higher Treg frequencies, particularly in HIV+ children. Regardless of antiretroviral therapy, HIV-infected children had a selective expansion of memory FOXP3+Helios+ Tregs. The rise in memory Tregs correlated with declining HIV clinical status, indicated by falling CD4 percentages and CD4:CD8 ratios and increasing HIV plasma viremia and IA. In addition, untreated HIV+ children exhibited an imbalance between the levels of Tregs and activated T cells. Finally, memory Tregs expressed IA markers CD38 and Ki67 and exhaustion marker, PD-1, that tightly correlated with a similar phenotype in memory CD4 T cells. Overall, HIV-infected children had significant disruptions of memory Tregs that associated with advancing HIV disease. J Acquir Immune Defic Syndr 2016 Aug 15; 72(5):474-84

Management of Facial Nerve Schwannoma: A Multicenter Study of 50 Cases

Objective  In the management of facial nerve schwannoma (FNS), surgical tumor resection is now often being replaced with more conservative approaches, such as observation with serial imaging or stereotactic radiosurgery (SRS). Given the scarcity of these lesions, determining the optimal management of FNS remains challenging and subject of debate with multiple treatment approaches supported in the literature. Methods  A retrospective chart review was performed in two academic centers for patients diagnosed with FNS between 1996 and 2017. The clinical presentation, treatment modalities employed, tumor control rates, and facial nerve function (FNF) outcomes (House–Brackmann system) were assessed and analyzed. Results  The study comprised 50 adult patients. Initial treatment modalities included observation with serial clinicoradiologic review in 27 patients (54%), surgery in 17 patients (34%), and SRS in 6 patients (12%). The FNF were decreased in more than half of the patients who had surgery. Nonetheless, more than 80% of the patients who were initially managed with observation or SRS had stable or improved FNF. Conclusion  A prevailing trend toward more conservative treatment modalities for FNS has evolved over time, providing relatively long-term preservation of FNF. As there are multiple management options available, it is of paramount importance that the treating physician be familiar with all treatment modalities and outcomes and counsel patients appropriately. The surgery should be reserved for large tumors and poor FNF at initial presentation or follow-up while watchful observation with imaging is the treatment of choice for rest of the patients