Against Acquired Immunodeficiency Syndrome Research Articles

A multi-layer photonic spiking neural network with a modified backpropagation algorithm for nonlinear classification

In this work, we construct a fully connected multi-layer photonic spiking neural network (PSNN) based on excitable vertical-cavity surface-emitting lasers with an embedded saturable absorber (VCSELs-SA) equipped with the modified supervised backpropagation (BP) algorithm. Different from the traditional BP algorithm, our proposed modified BP algorithm is based on optical spikes, and its activation function exploits the excitable characteristic of VCSELs-SA. It is demonstrated that this BP PSNN can be competent in linearly inseparable problems by correctly solving the exclusive or (XOR) problem. Thus, a three-layer fully connected BP PSNN is designed to perform the prediction of Human immunodeficiency virus-1 protease (HIV-1 PR) cleavage sites and achieves 91.95% classification accuracy with the modified BP algorithm, which could be a useful tool in helping to find effective inhibitors of HIV PR to fight against acquired immunodeficiency syndrome (AIDS). These results demonstrate the validity of our modified BP algorithm in dealing with nonlinear classification problems in PSNNs, which is helpful for supervised learning in the photonic neuromorphic computing architecture for future neuromorphic applications.

Therapeutic and Medicinal Properties of “The Silent Healer” Aloe vera (Aloe barbadensis Miller): A Systematic Review

The medicinal plants are widely recommended worldwide by the traditional and modern medical practitioners for curing various diseases of patients. Aloe vera is well known for its considerable medicinal properties. Aloe is widely used in wound healing, treating burns, minimizing frost bite damage, protection against skin damage from X-rays, lung cancer, intestinal problems, increasing High Density Lipoprotein (HDL), reducing Low Density Lipoprotein (LDL), reducing blood sugar in Diabetics, fighting against Acquired Immuno Deficiency Syndrome (AIDS), allergies and improving immune system. Aloe is used in traditional Indian medicine for constipation, colic, skin diseases, worm infestation, and infections. It is found in variety of commercial products such as, pills, sprays, ointments, lotions, liquids, drinks, jellies and creams. All these uses associated with Aloe vera have been attributed to the polysaccharides contained in the gel of the leaves. The chemistry of the plant has revealed that there are more than 200 different biologically active substances.

Sibr (Aloe barbadensis): A Short Description with Unani Approach

In many parts of world, there is still a tradition of using herbal drugs to combat various diseases & infections. Sibr is one of the essential components of Unani system of medicine and used by Unani physicians due to it’s a lot of medicinal properties since ancient time. It is commonly called Aloe-vera and belongs to the Lilicaceal family. It is a cactus like herb and grows in hot and arid environment. Unani physicians have been using this drug as a laxative, purgative (phlegm/bile), brain tonic, stomach tonic, liver tonic, emmenogogue, anti-inflammatory, blood purifier, antibacterial, and carminative agent. Hence, this drug having a vital place in Unani system of medicine and text. It is also use to reducing Low density Lipoprotein, increasing High density Lipoprotein, minimizing frost-bite injury, reducing blood glucose level, fighting against Acquired Immuno Deficiency Syndrome (AIDS), allergies, and boosting immune system. This article was designed to lime light the Aloe barbadensis by describing its brief toxicology, contraindications, traditional, therapeutic and others uses.
 Keywords: Antibacterial, Aloe barbadensis, Sibr, therapeutic, Unani system of medicine.

New Efavirenz Derivatives and 1,2,3-Triazolyl-phosphonates as Inhibitors of Reverse Transcriptase of HIV-1

According to the World Health Organization (WHO), the fight against Acquired Immunodeficiency Syndrome (AIDS) is still one of the most significant challenges facing humanity. Worldwide, it is estimated that 36.7 million people are infected by the Human Immunodeficiency Virus (HIV). Despite the variety of available drugs, the search for new enzymatic inhibitors of HIV is still important due to the presence of adverse effects and the development of resistant strains. Therefore, the present study aimed to design, synthesize, and biologically evaluate novel inhibitors of HIV Reverse Transcriptase (RT). These compounds were obtained in two series, and compounds in both series contain a 1,2,3-triazole ring in their structures. The compounds in the first series are Efavirenz (EFV) analogues with the N-1 position substituted by another important fragment as described in the medicinal chemistry literature on anti-HIV drugs. The second series has a phosphonate chain similar to that in the structure of Tenofovir Disoproxil Fumarate (TDF). The results of the biological evaluation showed that all compounds presented high RT inhibition values and lower or comparable inhibitory concentrations (the concentration needed to reduce the enzymatic activity by 50%, IC50 values, 0.8-1.9 µM). Among the compounds in the first series, the three with the lowest IC50 values had values between 0.8-0.9 µM, and of those in the second series, the most potent had an IC50 value of 1.1 µM; compounds in both series were equipotent to TDF (1.2 µM). Thus, the new compounds could be considered lead compounds for the development of new antiretroviral compounds.

Application of 3D-QSAR, Pharmacophore, and Molecular Docking in the Molecular Design of Diarylpyrimidine Derivatives as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors.

Diarylpyrimidines (DAPYs), acting as HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs), have been considered to be one of the most potent drug families in the fight against acquired immunodeficiency syndrome (AIDS). To better understand the structural requirements of HIV-1 NNRTIs, three-dimensional quantitative structure–activity relationship (3D-QSAR), pharmacophore, and molecular docking studies were performed on 52 DAPY analogues that were synthesized in our previous studies. The internal and external validation parameters indicated that the generated 3D-QSAR models, including comparative molecular field analysis (CoMFA, = 0.679, = 0.983, and = 0.884) and comparative molecular similarity indices analysis (CoMSIA, = 0.734, = 0.985, and = 0.891), exhibited good predictive abilities and significant statistical reliability. The docking results demonstrated that the phenyl ring at the C4-position of the pyrimidine ring was better than the cycloalkanes for the activity, as the phenyl group was able to participate in π–π stacking interactions with the aromatic residues of the binding site, whereas the cycloalkanes were not. The pharmacophore model and 3D-QSAR contour maps provided significant insights into the key structural features of DAPYs that were responsible for the activity. On the basis of the obtained information, a series of novel DAPY analogues of HIV-1 NNRTIs with potentially higher predicted activity was designed. This work might provide useful information for guiding the rational design of potential HIV-1 NNRTI DAPYs.

Assessment of Knowledge, Attitude and Belief of Medical Students towards AIDS Prevention and Transmission in Mashhad, Iran

Abstract Background: Iran is estimated to have about 73000 (50000-130000) people living with human immune deficiency virus (HIV) by end of 2015. Medical students are of special emphasis in agenda setting against Acquired Immunodeficiency Syndrome (AIDS). Objectives: The aim of this study was to assess the Knowledge, attitudes and practice of medical students to HIV/AIDS. Methods: This cross-sectional study was conducted among medical students in Mashhad, Iran in a six-month period at the second half of the year 2016. Stratified cluster random sampling technique was used to select 202 students in 4 courses of medical education. The world health organization’s instrument was used for assessing knowledge, attitudes, and beliefs about HIV/AIDS. One way ANOVA or Kruskal wallis test were used for data analysis. Results: The mean age of the subjects was 22.31+2.97 years. Most of them were male (65.7%) and 77.4% were single. Medical students had almost good general knowledge about HIV/AIDS. 28.9-98% answered correctly to this section. In transmission knowledge section there were some misconceptions about the routes of transmission and 15.6-98.5% answered correctly. The majority of students had positive attitudes toward HIV/AIDS, 74-98.2% of respondents answered correctly to this section. Overall 56-98% of students responded correctly to different beliefs domain questions. There were significant differences in mean knowledge score between four different courses of medical education (P=0.004). Conclusion: Findings indicated a statistically significant betterment in some aspect in knowledge, attitude and belief toward HIV/AIDs, but it was expected that final year medical students had more correct information, a fact not indicated in this study. Keywords: Attitude, Belief, HIV/AIDS, Knowledge, Medical Student

Dynamic and Electrostatic Effects on the Reaction Catalyzed by HIV-1 Protease.

HIV-1 Protease (HIV-1 PR) is one of the three enzymes essential for the replication process of HIV-1 virus, which explains why it has been the main target for design of drugs against acquired immunodeficiency syndrome (AIDS). This work is focused on exploring the proteolysis reaction catalyzed by HIV-1 PR, with special attention to the dynamic and electrostatic effects governing its catalytic power. Free energy surfaces for all possible mechanisms have been computed in terms of potentials of mean force (PMFs) within hybrid QM/MM potentials, with the QM subset of atoms described at semiempirical (AM1) and DFT (M06-2X) level. The results suggest that the most favorable reaction mechanism involves formation of a gem-diol intermediate, whose decomposition into the product complex would correspond to the rate-limiting step. The agreement between the activation free energy of this step with experimental data, as well as kinetic isotope effects (KIEs), supports this prediction. The role of the protein dynamic was studied by protein isotope labeling in the framework of the Variational Transition State Theory. The predicted enzyme KIEs, also very close to the values measured experimentally, reveal a measurable but small dynamic effect. Our calculations show how the contribution of dynamic effects to the effective activation free energy appears to be below 1 kcal·mol-1. On the contrary, the electric field created by the protein in the active site of the enzyme emerges as being critical for the electronic reorganization required during the reaction. These electrostatic properties of the active site could be used as a mold for future drug design.

Selection of a muramyl peptide based on its lack of activation of nuclear factor-kappa B as a potential adjuvant for AIDS vaccines.

Activation of the cellular transcription factor nuclear factor-kappa B (NF-kappa B) by cytokines and other immunostimulants has been tightly linked with enhanced replication of human immunodeficiency virus-type 1 (HIV-1) in infected cells. Various immunomodulators are currently being examined in animal and human trials for their suitability as adjuvants in potential vaccines against acquired immunodeficiency syndrome (AIDS). It may prove to be beneficial to select adjuvants that do not induce NF-kappa B activation and particularly if the vaccines are to be aimed at seropositive individuals. We have examined a battery of synthetic immunostimulants of the muramyl peptide family for their ability to activate NF-kappa B in human and mouse cell lines. In this report, we demonstrate selective activation of NF-kappa B in different cell lines and by different muramyl peptides possessing immunostimulatory activities. The mechanism of such activation is apparently via production of reactive oxygen intermediates (ROI) since pretreatment of cells with antioxidants blocked subsequent activation of NF-kappa B. However, among all the molecules tested only one lipophilic, non-pyrogenic adjuvant active muramyl peptide showed a complete lack of NF-kappa B activation in all cell lines tested. This molecule could well become the adjuvant of choice in future AIDS vaccines.

The role of the armadillo and sooty mangabey monkey in human leprosy

The armadillo was the first animal model of leprosy. Its role in the transmission of leprosy remains controversial. The sooty mangabey model of leprosy led to the discovery that rhesus monkeys were more susceptible to leprosy when coinfected with simian immunodeficiency virus (SIV), but that leprosy may play a protective role against acquired immunodeficiency syndrome (AIDS) mortality. Recently, molecular methods have been developed for leprosy and may help resolve the role of zoonoses in leprosy. The recent identification of a case of leprosy in a native-born American on the east coast of the USA and the identification of leprosy as an immunologic reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-positive cases raise the question of what role zoonoses may play in leprosy. Leprosy in armadillos and sooty mangabeys has been manipulated by human experimentation. In the case of the armadillo, further study, including molecular techniques, is required to elucidate the role of the armadillo as a zoonosis in human leprosy. Experimentation with the sooty mangabey led to the discovery of an interaction between SIV and leprosy in rhesus monkeys, and prompted the continued investigation of the relationship between HIV and leprosy.

Using case vignettes to measure HIV-related stigma among health professionals in China

We examined Chinese health professionals' attitudes towards patients with AIDS vs patients with hepatitis B. A representative sample of 1101 Chinese health professionals was used. Prejudicial attitudes and willingness to interact were measured based on two case vignettes. Statistical analyses revealed that health professionals had negative biases against acquired immunodeficiency syndrome (AIDS) patients and reported much less willingness to interact with AIDS patients than hepatitis B patients. Perceived risk of infection at work was also negatively associated with willingness to interact with patients with human immunodeficiency virus (HIV)/AIDS, but relationships varied by profession. This study underscores the importance of developing and implementing stigma reduction interventions in health care settings to address attitudinal biases and discrimination in clinical practice.

Macrophage Inflammatory Protein 1 and CCR5 as Attractive Therapeutic Targets for HIV Infection

Chemokines play key roles in inflammatory and immune responses mediated by their respective target cell populations. For instance, release of chemokines from inflammatory cells is a crucial step in the recruitment of cells needed to establish local inflammatory responses (e.g. rheumatoid arthritis). Moreover, recent advances in our understanding of the pathogenesis of human immunodeficiency virus (HIV) infection have revealed that chemokines and chemokine receptors are crucially involved in the molecular mechanism of HIV entry into target cells. Studies have shown that the chemokine receptor CCR5 serves as a critical coreceptor during the viral entry stage of HIV infection, while its ligands macrophage inflammatory protein (MIP)-1alpha and beta and RANTES act as endogenous inhibitors of HIV infection. This makes chemokine/chemokine receptor systems an attractive potential target for the development highly specific drugs with which to improve the management of HIV. This review will discuss the latest developments in the research on chemokine/chemokine receptor systems, especially MIP-1 and CCR5, with a particular focus on their role in the mechanism of HIV infection and on the development of effective therapies against acquired immunodeficiency syndrome (AIDS).

Application of 3D-QSAR Techniques in Anti-HIV-1 Drug Design - An Overview

Despite the availability of several classes of drugs against acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus type 1(HIV-1), this deadly disease showing very little sign of containment, especially in Sub-Saharan Africa and South-East Asia. More than 20 million people died since the first diagnosis of AIDS more than twenty years ago and almost 40 million people are currently living with HIV/AIDS. Structure-based drug design effort was immensely successful in identifying several drugs that are currently available for the treatment of HIV-1. Many applications have been reported on the use of quantitative structure-activity relationship (QSAR) studies to understand the drug-receptor interactions and help in the design of more effective analogs. Extensive application was also reported on the application of 3D-QSAR techniques, such as, Comparative Molecular Field Analysis (CoMFA), Comparative Molecular Similarity Analysis (CoMSIA), pharmacophore generation using Catalyst/HypoGen, free-energy binding analysis, GRID/GOLPE, HINT-based techniques, etc. in anti-HIV-1 drug discovery programs in academia and industry. We have attempted to put together a comprehensive overview on the 3D-QSAR applications in anti-HIV-1 drug design reported in the literature during the last decade.

Mucosal-targeted AIDS vaccines: the next generation?

Mucosal tissues are the predominant site for human immunodeficiency virus (HIV)-1 infection and replication, and mucosal immunization strategies might be essential to elicit an effective vaccine against acquired immunodeficiency syndrome (AIDS). The subversion of dendritic cells (DCs) by HIV-1 for mucosal transmission has designated these cells as promising targets for intervention. Strikingly, DCs might also be important for inducing mucosal-specific immunity. Here we will discuss the different roles that DCs play in mucosal HIV-1 transmission and AIDS vaccine development.

Knowledge and attitude towards HIV/AIDS among Iranian students.

BackgroundYoung people are of particular importance in state policies against Acquired Immunodeficiency Syndrome (AIDS). We intended to assess the knowledge and attitude of high school students regarding AIDS in Iran.MethodsThrough a cluster-sampling, 4641 students from 52 high schools in Tehran were assessed by anonymous questionnaires in February 2002.ResultsThe students identified television as their most important source of information about AIDS. Only a few students answered all the knowledge questions correctly, and there were many misconceptions about the routes of transmission. Mosquito bites (33%), public swimming pools (21%), and public toilets (20%) were incorrectly identified as routes of transmission. 46% believed that Human Immunodeficiency Virus positive (HIV positive) students should not attend ordinary schools. Most of the students wanted to know more about AIDS. In this study knowledge level was associated with students' attitudes and discipline (p < 0.001).ConclusionAlthough the knowledge level seems to be moderately high, misconceptions about the routes of transmission were common. There was a substantial intolerant attitude towards AIDS and HIV positive patients. We recommend that strategies for AIDS risk reduction in adolescents be developed in Iranian high schools.

Religious Affiliation and Social Commitment as Determinants of Moral Attitudes in the Prevention of AIDS or the Fight Against Poverty

The present study is an analysis of the effect of religious affiliation and social commitment on moral attitudes in the fight against acquired immunodeficiency syndrome (AIDS) or the fight against poverty. French citizens (N = 284) who either belonged to the Roman Catholic church or were without religious affiliation, who were committed to the prevention of AIDS or to the fight against poverty, completed a 9-item scale drawn from R. C. Katz, J. Santman, and P. Lonero's (1994) Morally Debatable Behaviors Scale-Revised. Results indicated that the responses were significantly affected by the religious affiliation and beliefs of respondents: Roman Catholics expressed less moral tolerance than nonreligious respondents. An interaction between commitment and religious belief showed that Roman Catholics committed to the fight against AIDS were less tolerant of illegal conduct than those committed to the fight against poverty, whereas no difference appeared between nonreligious respondents. No gender effect appeared.

Pathology of human immunodeficiency virus infection: noninfectious conditions.

Diagnostic anatomic pathologists play a crucial role in the battle against acquired immunodeficiency syndrome (AIDS). Not only are they intimately involved in the treatment of individual patients with human immunodeficiency virus (HIV) infection, but also they make important observations that result in the expansion of the scientific understanding of its pathogenesis. Pathologists studying tissue from patients with HIV infection should be familiar with the conditions to which these patients are susceptible. Although opportunistic infections are important causes of morbidity and mortality, noninfectious conditions frequently make substantial contributions to the disease course. Patients with HIV infection may be at increased risk for neoplastic disease. They do not, however, have an increased incidence of the most common tumors affecting the general population, such as breast, colon, and prostate carcinoma. Immunodeficiency results in increased susceptibility to malignant neoplasms, both by decreased immunologic response to abnormal cells and increased susceptibility to infection by viruses. All of the malignant neoplastic diseases that are Centers for Disease Control and Prevention (CDC) AIDS indicator conditions have been shown to have an association with a virus: Kaposi sarcoma (KS) with herpes hominis virus 8 (HHV-8), malignant lymphoma with Epstein-Barr virus (EBV), and cervical carcinoma with human papilloma virus (HPV). Patients with HIV infection also can develop reactive processes that are attributable to direct effects of HIV or immune system alterations. Such conditions include salivary gland cystic lymphoepithelial lesion, lymphadenopathy, lymphocytic interstitial pneumonitis, encephalopathy, enteropathy, nephropathy, hepatic conditions, dermatologic conditions and anemia.

A live-virus "suicide" vaccine for human immunodeficiency virus.

A vaccine that uses a live, attenuated human immunodeficiency virus (HIV) may offer the best hope of a vaccine against acquired immunodeficiency syndrome (AIDS). A recent improvement should increase the safety of the live-virus approach: a "suicide gene" inserted into the viral RNA, which causes infected cells to die when treated with ganciclovir. We envision using this strategy not only to prevent AIDS, but also to treat it.

A Perspective on AIDS Vaccines

To many people it is unfathomable that after more than 10 years of research, there is no human immunodeficiency virus (HIV) vaccine ready for large-scale efficacy trials. A complex web of scientific, political, and social issues remains to be untangled. Barry Bloom (Howard Hughes Medical Institute, Albert Einstein College of Medicine, USA) takes a hard look at the fundamental questions that must be answered before a vaccine against acquired immunodeficiency syndrome (AIDS) becomes a reality.

Recombinant subunit vaccines as an approach to study correlates of protection against primate lentivirus infection

Using pathogenic simian immunodeficiency virus (SIV) infection of macaques as a model, we explored the limits of the protective immunity elicited by recombinant subunit vaccines and examined factors that affect their efficacy. Envelope gp 160 vaccines, when used in a live recombinant virus-priming and subunit-protein-boosting regimen, protected macaques against a low-dose, intravenous infection by a cloned homologous virus SIV mne E11S. The same regimen was also effective against intrarectal challenge by the same virus and against intravenous challenge by E11S grown on primary macaque peripheral blood mononuclear cells (PBMC). However, only limited protection was observed against uncloned SIV mne. Priming with live recombinant virus was more effective than immunization with subunit gp 160 alone, indicating a potential advantage of native antigen presentation and the possible role of cell-mediated immunity in protection. Whole gp 160 was more effective than the surface antigen (gp130), even though both antigens elicited similar levels of neutralizing antibodies. Animals immunized with the core ( gag-pol) antigens failed to generate any neutralizing antibody and were all infected following challenge. However, their proviral load was 10–100-fold lower than that of the control animals, indicating that immune mechanisms such as cytotoxic T lymphocytes (CTL) may play a role. Finally, animals immunized with both the core and the envelope antigens generated significant protective immunity, even with relatively low neutralizing antibodies. Taken together, these results indicate that multiple mechanisms may contribute to protection. It may therefore be advantageous to incorpotate multiple antigens in the design of recombinant subunit vaccines against acquired immunodeficiency syndrome (AIDS).

The risk of domestic violence and women with HIV infection: implications for partner notification, public policy, and the law.

Partner notification has emerged as an important strategy in the fight against acquired immunodeficiency syndrome (AIDS), and states have now adopted a plethora of laws that encourage or mandate notification, often without the patient's consent. As human immunodeficiency virus (HIV) infection continues to spread among women, the future development of AIDS control strategies and public health laws must be shaped by concern for the safety and autonomy of patients who face a risk of domestic violence. Three distinct recommendations flow from this premise. First, all HIV-infected women should be assessed for the risk of domestic violence and offered appropriate interventions. Second, where a risk of abuse is indicated, partners should never be notified without the patient's consent. State laws that presently permit involuntary notification should be repealed or amended. Third, laws that punish a patient's refusal to notify partners should also be modified or repealed.