Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120

BACKGROUND: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus. METHODS: Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope. RESULTS: 1) CAP binds to HIV-1 virus particles and to the envelope glycoprotein gp120; 2) this leads to blockade of the gp120 V3 loop and other gp120 sites resulting in diminished reactivity with HIV-1 coreceptors CXCR4 and CCR5; 3) CAP binding to HIV-1 virions impairs their infectivity; 4) these findings apply to both HIV-1 IIIB, an X4 virus, and HIV-1 BaL, an R5 virus. CONCLUSIONS: These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection

Can COVID 19 present like appendicitis?

Coronavirus disease -19 is a novel pandemic contagious respiratory infection that frequently presents with fever and dry cough. However, it can present with other rare symptoms. As this disease is a new disease, the full picture of the disease presentation is not yet clear, and it might present with symptoms and signs of other common diseases. Here, we report a 40 year old female who presented with acute onset nausea, vomiting, loss of appetite and vague abdominal pain as a clinical picture of appendicitis, but her CT abdomen image showed normal appendix, bilateral patchy peripheral lung basal consolidation, and ground-glass attenuation, so she was tested for coronavirus disease-19, which was positive

Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

<b>BACKGROUND:</b> In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.<p></p> <b>RESULTS:</b> Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.<p></p> <b>CONCLUSIONS:</b> The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.<p></p&gt

Impact of chemotherapy for HIV-1 related lymphoma on residual viremia and cellular HIV-1 DNA in patients on suppressive antiretroviral therapy

The first cure of HIV-1 infection was achieved through complex, multimodal therapy including myeloablative chemotherapy, total body irradiation, anti-Thymocyte globulin, and allogeneic stem cell transplantation with a CCR5 delta32 homozygous donor. The contributions of each component of this therapy to HIV-1 eradication are unclear. To assess the impact of cytotoxic chemotherapy alone on HIV-1 persistence, we longitudinally evaluated low-level plasma viremia and HIV-1 DNA in PBMC from patients in the ACTG A5001/ALLRT cohort on suppressive antiretroviral therapy (ART) who underwent chemotherapy for HIV-1 related lymphoma without interrupting ART. Plasma HIV-1 RNA, total HIV-1 DNA and 2-LTR circles (2-LTRs) in PBMC were measured using sensitive qPCR assays. In the 9 patients who received moderately intensive chemotherapy for HIV-1 related lymphoma with uninterrupted ART, low-level plasma HIV-1 RNA did not change significantly with chemotherapy: median HIV-1 RNA was 1 copy/mL (interquartile range: 1.0 to 20) pre-chemotherapy versus 4 copies/mL (interquartile range: 1.0 to 7.0) post-chemotherapy. HIV-1 DNA levels also did not change significantly, with median prechemotherapy HIV-1 DNA of 355 copies/106 CD4+ cells versus 228 copies/106 CD4+ cells post-chemotherapy. 2-LTRs were detectable in 2 of 9 patients pre-chemotherapy and in 3 of 9 patients post-chemotherapy. In summary, moderately intensive chemotherapy for HIV-1 related lymphoma in the context of continuous ART did not have a prolonged impact on HIV-1 persistence. © 2014 Cillo et al

Detecting spam using Harris Hawks optimizer as a feature selection algorithm

The Harris Hawks optimization (HHO) was used in this study to enhance spam identification. Only the features with a high influence on spam detection have been selected using the HHO metaheuristic technique. The HHO technique's assessment of the selected features was conducted using the ISCX-URL2016 dataset. The ISCX-URL2016 dataset has 72 features, but the HHO technique reduces that to just 10 features. Extra tree (ET), extreme gradient boosting (XGBoost), and support vector machine (SVM) techniques are used to complete the classification assignment. 99.81% accuracy is attained by the ET, 99.60% by XGBoost, and 98.74% by SVM. As we can see, with the ET, XGBoost, and k-nearest neighbor (KNN) techniques, the HHO technique achieves accuracy above 98%. Nonetheless, the ET technique outperforms the XGBoost and KNN techniques. ET outperforms other methods due to its robust ensemble approach, which benefits from the diverse and relevant feature subset selected by HHO. HHO's effective reduction of noisy or redundant features enhances ET's ability to generalize and avoid overfitting, making it a highly efficient combination for spam detection. Thus, it looks promising to combat spam emails by combining the ET technique for classification with the HHO technique for feature selection

Psychometric properties of the Arabic version of the good death inventory (GDI-A) questionnaire tested on Palestinian family members of deceased adult cancer patients

Background Despite the importance of understanding the concept of good death (GD) from different cultural perspectives, it has not been assessed in Arab communities because of the unavailability of validated instruments. This study aimed to evaluate the psychometric properties of the Arabic version of the Good Death Inventory (GDI-A) questionnaire used among Palestinian bereaved family members of cancer patients. Methods A cross-sectional methodological study was applied. An online survey was adopted as a data collection method. The online survey was delivered through Qualtrics and posted in cancer and health-related social media groups on Facebook, the most commonly utilized social media platform in Palestine. A convenient and snowball sampling of 285 family members of deceased adult cancer patients was adopted. The participants were asked to complete GDI online survey. A confirmatory factor analysis (CFA), content validity, and internal consistency reliability were assessed. Results Participants showed a good perspective about death (M = 300.01, SD = 31.09). Significant differences in GDI-A total score were reported with the “patient’s relationship with family” (M = 303.02, SD = 31.42), F(2, 282) = 7.787, p = .001, “educational level” (M = 305.97, SD = 28.38), F(4, 280) = 3.685, p = .006, and “member’s relationship with the patient” (M = 311.74, SD = 16.57), F(5, 279) = 3.125, p = .009. The Arabic version scale-level content validity index and the scale-level content validity index-universal agreement were 0.96 and 0.85, respectively. Factor analysis with a varimax rotation matrix revealed that 16 factors explained 76.08% of the variance. Conclusion This study provides the literature with an Arabic questionnaire for understanding the concept of a GD from the perspective of bereaved families. The GDI Arabic translated version is a psychometrically robust instrument with satisfactory measurement, which can be used for evaluating a GD among bereaved families

Using death to one's advantage: HIV modulation of apoptosis

Infection by human immunodeficiency virus (HIV) is associated with an early immune dysfunction and progressive destruction of CD4+ T lymphocytes. This progressive disappearance of T cells leads to a lack of immune control of HIV replication and to the development of immune deficiency resulting in the increased occurrence of opportunistic infections associated with acquired immune deficiency syndrome (AIDS). The HIV-induced, premature destruction of lymphocytes is associated with the continuous production of HIV viral proteins that modulate apoptotic pathways. The viral proteins, such as Tat, Env, and Nef, are associated with chronic immune activation and the continuous induction of apoptotic factors. Viral protein expression predisposes lymphocytes, particularly CD4+ T cells, CD8+ T cells, and antigen-presenting cells, to evolve into effectors of apoptosis and as a result, to lead to the destruction of healthy, non-infected T cells. Tat and Nef, along with Vpu, can also protect HIV-infected cells from apoptosis by increasing anti-apoptotic proteins and down- regulating cell surface receptors recognized by immune system cells. This review will discuss the validity of the apoptosis hypothesis in HIV disease and the potential mechanism(s) that HIV proteins perform in the progressive T cell depletion observed in AIDS pathogenesis. Originally published Leukemia, Vol. 15, No. 3, Mar 200

PI3Kδ and primary immunodeficiencies.

Primary immunodeficiencies are inherited disorders of the immune system, often caused by the mutation of genes required for lymphocyte development and activation. Recently, several studies have identified gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (which encodes p110δ) and PIK3R1 (which encodes p85α) that cause a combined immunodeficiency syndrome, referred to as activated PI3Kδ syndrome (APDS; also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (PASLI)). Paradoxically, both loss-of-function and gain-of-function mutations that affect these genes lead to immunosuppression, albeit via different mechanisms. Here, we review the roles of PI3Kδ in adaptive immunity, describe the clinical manifestations and mechanisms of disease in APDS and highlight new insights into PI3Kδ gleaned from these patients, as well as implications of these findings for clinical therapy

Removal of fluoride using quaternized palm kernel shell as adsorbents: Equilibrium isotherms and kinetics studies

Palm kernel shell (PKS) core fibers, an agricultural waste, were chemically modified using N-(3-chloro-2-hydroxypropyl) trimethylammonium chloride (CHMAC) as a quaternizing agent. The potential of quaternized palm kernel shell (QPKS) as an adsorbent for fluoride in an aqueous solution was then studied. The quaternized palm kernel shell (QPKS) core fibers were characterized using Fourier transform infrared spectroscopy (FTIR) and a scanning electron microscope (SEM). The effect of various factors on the fluoride sequestration was also investigated. The results showed that with an increase in the adsorbent amount and contact time, the efficiency of fluoride removal was improved. The maximum fluoride uptake was obtained at pH 3 and a contact time of 4 h. The adsorption behavior was further investigated using equilibrium isotherms and kinetics studies. The results from these studies fit well into Freundlich, Redlich-Peterson, and Sips isotherm's with a coefficient of determination (R2) of 0.9716. The maximum fluoride removal was 63%. For kinetics studies, the pseudo-second order was the best fit for fluoride, with an R2 of 0.999. These results suggest that QPKS has the potential to serve as a low-cost adsorbent for fluoride removal from aqueous solutions