艾滋病PA检测图像的处理与分析

针对目前普遍使用的艾滋病PA检测法的结果判定问题,提出一种用于艾滋病PA检测的图像处理方法.在对PA检测图像进行去噪、去背景处理后,利用最大类间方差法对图像进行分割,得到面积、周长、质心等参数,进而给出艾滋病诊断结果.该方法可减少人眼误判,提高艾滋病诊断的正确率,同时也适用于其他疾病PA检测的图像分析.     

Sirtuins Modulation: A Promising Strategy for HIV-Associated Neurocognitive Impairments

HIV-Associated neurocognitive disorder (HAND) is one of the major concerns since it persists in 40% of this population. Nowadays, HAND neuropathogenesis is considered to be caused by the infected cells that cross the brain–blood barrier and produce viral proteins that can be secreted and internalized into neurons leading to disruption of cellular processes. The evidence points to viral proteins such as Tat as the causal agent for neuronal alteration and thus HAND. The hallmarks in Tat-induced neurodegeneration are endoplasmic reticulum stress and mitochondrial dysfunction. Sirtuins (SIRTs) are NAD+-dependent deacetylases involved in mitochondria biogenesis, unfolded protein response, and intrinsic apoptosis pathway. Tat interaction with these deacetylases causes inhibition of SIRT1 and SIRT3. Studies revealed that SIRTs activation promotes neuroprotection in neurodegenerative diseases such Alzheimer’s and Parkinson’s disease. Therefore, this review focuses on Tat-induced neurotoxicity mechanisms that involve SIRTs as key regulators and their modulation as a therapeutic strategy for tackling HAND and thereby improving the quality of life of people living with HIV.     

Vif-ΔN28和Cullin5-N138蛋白的表达及纯化

目的获得高纯度的Vif-ΔN28和Cullin5-N138蛋白。方法以Vif/VR1012质粒为模板,PCR扩增出Vif-ΔN28基因并插入pRSETB质粒。将构建的原核表达载体Vif-ΔN28/pRSETB以及已有的Cullin5-N138/pRSETB质粒分别转化大肠杆菌BL21(DE3),经IPTG诱导表达,产物经Ni-NTA离子纯化柱纯化、复性。结果所表达的Vif-ΔN28和Cullin5-N138蛋白约占各自菌体总蛋白的20%,纯化后蛋白纯度均可达90%以上。结论已成功构建了Vif-ΔN28原核表达质粒,并在大肠杆菌中高效表达,获得了可溶性的纯化的Vif-ΔN28和Cullin5-N138蛋白。     

Novel Monocyclam Derivatives as HIV Entry Inhibitors: Design,Synthesis, Anti‐HIV Evaluation,and Their Interaction with the CXCR4 Co‐receptor

The CXCR4 receptor has been shown to interact with the human immunodeficiency virus (HIV) envelope glycoprotein gp120, leading to fusion of viral and cell membranes. Therefore, ligands that can attach to this receptor represent an important class of therapeutic agents against HIV, thus inhibiting the first step in the cycle of viral infection: the virus–cell entry/fusion. Herein we describe the in silico design, synthesis, and biological evaluation of novel monocyclam derivatives as HIV entry inhibitors. In vitro activity testing of these compounds in cell cultures against HIV strains revealed EC₅₀ values in the low micromolar range without cytotoxicity at the concentrations tested. Docking and molecular dynamics simulations were performed to predict the binding interactions between CXCR4 and the novel monocyclam derivatives. A binding mode of these compounds is proposed which is consistent with the main existing site‐directed mutagenesis data on the CXCR4 co‐receptor. Moreover, molecular modeling comparisons were performed between these novel monocyclams, previously reported non‐cyclam compounds from which the monocyclams are derived, and the well‐known AMD3100 bicyclam CXCR4 inhibitors. Our results suggest that these three structurally diverse CXCR4 inhibitors bind to overlapping but not identical amino acid residues in the transmembrane regions of the receptor.     

Host Restriction Factors Modulating HIV Latency and Replication in Macrophages

In addition to CD4⁺ T lymphocytes, myeloid cells and, particularly, differentiated macrophages are targets of human immunodeficiency virus type-1 (HIV-1) infection via the interaction of gp120Env with CD4 and CCR5 or CXCR4. Both T cells and macrophages support virus replication, although with substantial differences. In contrast to activated CD4⁺ T lymphocytes, HIV-1 replication in macrophages occurs in nondividing cells and it is characterized by the virtual absence of cytopathicity both in vitro and in vivo. These general features should be considered in evaluating the role of cell-associated restriction factors aiming at preventing or curtailing virus replication in macrophages and T cells, particularly in the context of designing strategies to tackle the viral reservoir in infected individuals receiving combination antiretroviral therapy. In this regard, we will here also discuss a model of reversible HIV-1 latency in primary human macrophages and the role of host factors determining the restriction or reactivation of virus replication in these cells.     

CD8+ T Cell Senescence: Lights and Shadows in Viral Infections,Autoimmune Disorders and Cancer

CD8⁺ T lymphocytes are a heterogeneous class of cells that play a crucial role in the adaptive immune response against pathogens and cancer. During their lifetime, they acquire cytotoxic functions to ensure the clearance of infected or transformed cells and, in addition, they turn into memory lymphocytes, thus providing a long-term protection. During ageing, the thymic involution causes a reduction of circulating T cells and an enrichment of memory cells, partially explaining the lowering of the response towards novel antigens with implications in vaccine efficacy. Moreover, the persistent stimulation by several antigens throughout life favors the switching of CD8⁺ T cells towards a senescent phenotype contributing to a low-grade inflammation that is a major component of several ageing-related diseases. In genetically predisposed young people, an immunological stress caused by viral infections (e.g., HIV, CMV, SARS-CoV-2), autoimmune disorders or tumor microenvironment (TME) could mimic the ageing status with the consequent acceleration of T cell senescence. This, in turn, exacerbates the inflamed conditions with dramatic effects on the clinical progression of the disease. A better characterization of the phenotype as well as the functions of senescent CD8⁺ T cells can be pivotal to prevent age-related diseases, to improve vaccine strategies and, possibly, immunotherapies in autoimmune diseases and cancer.     

A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected individuals.

Objective: To evaluate cognitive-behavioral therapy to enhance medication adherence and reduce depression (CBT-AD) in individuals with HIV. Design: A two arm, randomized, controlled, cross-over trial comparing CBT-AD to enhanced treatment as usual only (ETAU). ETAU, which both groups received, included a single-session intervention for adherence and a letter to the patient's provider documenting her or his continued depression. The intervention group also received 10 to 12 sessions of CBT-AD. Main Outcome Measures: Adherence to antiretroviral therapy as assessed by Medication Event Monitoring Systems (MEMs) and depression as assessed by blinded structured evaluation. Results: At the acute outcome assessment (3-months), those who received CBT-AD evidenced significantly greater improvements in medication adherence and depression relative to the comparison group. Those who were originally assigned to the comparison group who chose to cross over to CBT-AD showed similar improvements in both depression and adherence outcomes. Treatment gains for those in the intervention group were generally maintained at 6- and 12-month follow-up assessments. By the end of the follow-up period, those originally assigned CBT-AD demonstrated improvements in plasma HIV RNA concentrations, though these differences did not emerge before the cross-over, and hence there were not between-groups differences. Conclusions: CBT-AD is a potentially efficacious approach for individuals with HIV struggling with depression and adherence. Replication and extension in larger efficacy trials are needed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modulation of Viscoelasticity and HIV Transport as a Function of pH in a Reversibly Crosslinked Hydrogel

Materials that respond to physiological stimuli are important in developing advanced biomaterials for modern therapies. The reversibility of covalent crosslinks formed by phenylboronate (PBA) and salicylhydroxamate (SHA) has been exploited to provide a pH‐responsive gel for application to the vaginal tract. Dynamic rheology reveals that the gel frequency‐dependent viscoelastic properties are modulated by pH. At pH 4.8 the viscous component dominates throughout most of the frequency range. As the pH increases, the characteristic relaxation time continues to increase while the G′_Plateau levels off above pH 6. At pH 7.5, the elastic component dominates throughout the frequency sweep and is predominately independent of frequency. Particle tracking assesses the transport of both fluorescently labeled HIV‐1 and 100‐nm latex particles in the PBA–SHA crosslinked gel as a function of pH. At pH 4.8 the ensemble‐averaged mean squared displacement at lag times greater than three seconds reveals that transport of the HIV‐1 and 100‐nm particles becomes significantly impeded by the matrix, exhibiting diffusion coefficients less than 0.0002 µm² s^?1. This pH‐responsive gel thus displays properties that have the potential to significantly reduce the transport of HIV‐1 to susceptible tissues and thus prevent the first stage of male‐to‐female transmission of HIV‐1.     

A social problem-solving model of adherence to HIV medications.

HIV medication adherence remains a challenge and limits the degree to which treatment benefit can be maximized. This study tested an explanatory model of HIV medication adherence using a social problem-solving (SPS) framework. Associations of SPS with adherence are hypothesized to be direct and/or indirect via psychological health. HIV+ adults were interviewed using validated measures of SPS, psychological health, and antiretroviral therapy (ART) medication adherence. Structural equation modeling (SEM) techniques were used to test hypothesized relationships and to evaluate overall fit of the model to the data. SEM supported an indirect association (but not direct) of SPS on adherence via psychological health among the 545 HIV+ adults included in the analyses. Overall, the findings resulted in a model of adherence that offered very good fit to the data and correctly classified 97% of the cases as adherent versus nonadherent. Results support the use of SPS as a conceptual framework for understanding adherence to ART. Findings offer rationale and direction for SPS interventions to enhance adherence by improving psychological health. Such approaches, if effective, have the potential to positively impact psychological well being and adherence, thereby maximizing clinical benefit from treatment, which is linked to lower mortality from AIDS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A tutorial on biomedical process control

This paper presents a tutorial on five typical applications within the area of biomedical process control. The specific applications discussed include: control of insulin administration for treating diabetes mellitus, dynamic modeling for anti-cancer chemotherapy regimen design, modeling and control of drug infusion in critical care, structured treatment interruptions: a control mathematical approach to AIDS protocol design, and dynamic modeling and control of the anticoagulant drug heparin. The objective of the tutorial is to illustrate the rich and important set of problems within the biomedical area that process control engineers can contribute to solving. Solution to these problems can have a significant medical as well as economic impact.