Low-Level HIV-I Replication and the Dynamics of the Resting CD4(+) T Cell Reservoir for HIV-I in the Setting of HAART

In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-I (HIV-I) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4(+) T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-I infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells. Methods: Here we use a mathematical model of T cell dynamics in the setting of HIV-I infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART. Results: By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model. Conclusion: The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-I infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.NIH AI 065960, AI 143222, AI 51178Doris Duke Charitable FoundationThe Howard Hughes Medical InstituteIntegrative Biolog

Low-level HIV-1 replication and the dynamics of the resting CD4+ T cell reservoir for HIV-1 in the setting of HAART

<p>Abstract</p> <p>Background</p> <p>In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4⁺T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells.</p> <p>Methods</p> <p>Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART.</p> <p>Results</p> <p>By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model.</p> <p>Conclusion</p> <p>The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.</p

Determinants of healthcare utilisation and predictors of outcome in colorectal cancer patients from Northern Iran

We aimed to assess healthcare utilisation (HU), its determinants, as well as its relationship with survival in colorectal cancer (CRC) patients. This study was conducted on incident CRC cases from Northern Iran. Information on HU was collected using a valid questionnaire, considering eight diagnostic and four therapeutic services. The results were categorised as good and poor HU. Multivariate logistic regression analysis was used to assess the relationship between HU and other variables. Cox regression analysis was performed to determine major predictors of survival. In total, 227 new cases of CRC were enrolled. HU could be assessed in 218 subjects (96). Living in rural areas was the strongest variable related to poor HU (adjusted OR, odds ratio=2.65; CI, confidence interval: 1.30-5.40). The median survival time was 40.5months. The 1-, 3- and 5-year survival rates were 71, 52 and 44 respectively. Cox regression analysis showed a significant lower survival rate in patients with poor HU (HR=2.3; CI: 1.46-3.64). HU was an independent predictor of survival in our CRC patients. Patients' place of residence was a significant determinant of HU. Regarding its effects on patients' outcome, HU and its determinants should be considered in designing CRC controlling programmes in our region and similar high-risk populations. © 2016 John Wiley & Sons Ltd

Postconditioning is protective in renal reperfusion injury only in male rats. A gender difference study

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Ability of biofilm production and molecular analysis of spa and ica genes among clinical isolates of methicillin-resistant Staphylococcus aureus

Objective: This study aimed to evaluate the phenotypic and genotypic characterization of biofilm formation and spa and ica genes among clinical isolates of methicillin-resistant Staphylococcus aureus. Result: This cross-sectional study was performed on 146 Staphylococcus aureus isolates from hospitalized patients in Isfahan Province Hospitals. MRSA isolates were confirmed using disk diffusion test with oxacillin disk and amplification of mecA gene by PCR assays. Ability of biofilm production was evaluated targeting the icaA and icaD genes. Of 146 Staphylococcus aureus isolates, 24 (16.4) carried mecA genes and identified as MRSA strains. Strong ability of biofilm production was seen among 76.02 (111/146) S. aureus isolates and 87.5 (21/24) MRSA strains, respectively. Also, 75.0 (18/24) MRSA isolates carried icaA and icaD was not detected in these strains. Analysis of spa gene showed 70.83 (17/24) MRSA strains were spa positive. From which 14 and 3 strains identified with one band (150, 270, 300, 360, 400 bp) and two bands (150-300 bp), respectively. According to data obtained, the prevalence of MRSA isolates from Isfahan Province Hospitals is relatively high and a remarkable percentage of them show strong power in biofilm production. Also analysis of spa gene showed a fairly large diversity among MRSA strains. © 2020 The Author(s)

Association between socio-demographic factors and diabetes mellitus in the north of Iran: A population-based study

Objective: This study considers the prevalence of DM and some related factors among adults in the Golestan province (north of Iran) in 2006. Methods: This is a Cross-sectional-Descriptive and population-based study, carried out among 1999 cases (1000 men and 999 women) between 25 and 65 years old. Participants were chosen by cluster and stratified sampling in urban and rural areas. Data on socio-demographic factors were collected using questionnaire, and anthropometric and biochemical indexes were measured. Fasting Blood Sugar (FBS) equal to or over 126 mg/dl was classified as type 2 DM. Results: Mean of age was 39.2 years and mean ± SD of FBS among men and women was 94.51 ± 32.91 and 98.2 ± 40.1 mg/dl, respectively. Prevalence of DM was 8.3% [(men = 6.8% and women = 9.7%), (urban = 10.5% and villages = 6.4%)]. Twenty-five percent of patients were undiagnosed as whole, 43% of patients were unaware of their problem, in men more than in women (48.5% versus 39.2%) and in rural area more than in urban area (35.1% versus 54.4%). We showed a positive and significant correlation between FBS and age, waist circumference and BMI (P = 0.01). Conclusion: DM was the one of the biggest health problems in the north of Iran, and half of them were unaware of their morbidity. DM was influenced by socio-demographic factors. © 2010 International Journal of Diabetes Mellitus. Published by Elsevier Ltd. All rights reserved

Limits on Replenishment of the Resting CD4+ T Cell Reservoir for HIV in Patients on HAART

Whereas cells productively infected with human immunodeficiency virus type 1 (HIV-1) decay rapidly in the setting of highly active antiretroviral therapy (HAART), latently infected resting CD4+ T cells decay very slowly, persisting for the lifetime of the patient and thus forming a stable reservoir for HIV-1. It has been suggested that the stability of the latent reservoir is due to low-level viral replication that continuously replenishes the reservoir despite HAART. Here, we offer the first quantitative study to our knowledge of inflow of newly infected cells into the latent reservoir due to viral replication in the setting of HAART. We make use of a previous observation that in some patients on HAART, the residual viremia is dominated by a predominant plasma clone (PPC) of HIV-1 not found in the latent reservoir. The unique sequence of the PPC serves as a functional label for new entries into the reservoir. We employ a simple mathematical model for the dynamics of the latent reservoir to constrain the inflow rate to between 0 and as few as 70 cells per day. The magnitude of the maximum daily inflow rate is small compared to the size of the latent reservoir, and therefore any inflow that occurs in patients on HAART is unlikely to significantly influence the decay rate of the reservoir. These results suggest that the stability of the latent reservoir is unlikely to arise from ongoing replication during HAART. Thus, intensification of standard HAART regimens should have minimal effects on the decay of the latent reservoir

Biomechanical analysis of temporomandibular joint dynamics based on real-time magnetic resonance imaging

Aim: The traditional hinge axis theory of temporomandibular joint (TMJ) dynamics is increasingly being replaced by the theory of instantaneous centers of rotation (ICR). Typically, ICR determinations are based on theoretical calculations or three-dimensional approximations of finite element models. Materials and methods: With the advent of real-time magnetic resonance imaging (MRI), natural physiologic movements of the TMJ may be visualized with 15 frames per second. The present study employs real-time MRI to analyze the TMJ biomechanics of healthy volunteers during mandibular movements, with a special emphasis on horizontal condylar inclination (HCI) and ICR pathways. The Wilcoxon rank sum test was used to comparatively analyze ICR pathways of mandibular opening and closure. Results: Mean HCI was 34.8 degrees (± 11.3 degrees) and mean mandibular rotation was 26.6 degrees (± 7.2 degrees). Within a mandibular motion of 10 to 30 degrees, the resulting x- and y-translation during opening and closure of the mandible differed significantly (10 to 20 degrees, x: P = 0.02 and y: P 30 degrees showed no significant differences in x- and y-translation. Near occlusion movements differed only for y-translation (P < 0.01). Conclusion: Real-time MRI facilitates the direct recording of TMJ structures during physiologic mandibular movements. The present findings support the theory of ICR. Statistics confirmed that opening and closure of the mandible follow different ICR pathways, which might be due to muscular activity discrepancies during different movement directions. ICR pathways were similar within maximum interincisal distance (MID) and near occlusion (NO), which might be explained by limited extensibility of tissue fibers (MID) and tooth contact (NO), respectively