Analysis of primary resistance mutations to HIV-1 entry inhibitors in therapy naive subtype C HIV-1 infected mother– infant pairs from Zambia

Background—Small molecular CCR5 inhibitors represent a new class of drugs for treating HIV-1 infection. The evaluation of the primary resistance mutations associated with entry inhibitors during HIV-1 perinatal transmission is required because they may have a profound impact on the clinical management in MTCT. Objectives—To evaluate the primary resistance mutations to maraviroc and vicriviroc during perinatal transmission and analyze the sensitivity of Env derived from mother–infant pairs to maraviroc. Study design—Nine MIPs infected by subtype C HIV-1 were recruited to analyze the prevalence and transmission of primary resistance mutations to maraviroc and vicriviroc. Moreover, Env derived from six MIPs were employed to construct provirus clones and to analyze the sensitivity to maraviroc. Results—Mutations A316T, conferring partial resistance to maraviroc, T307I and R315Q, both conferring partial resistance to vicriviroc are prevalent in mother and infant cohorts, indicating the transmission of primary resistance mutations during HIV-1 perinatal transmission. However, the mutations of acutely infected mothers seem to directly transmit to their corresponding infants, while some mutations at low frequency of chronically infected mothers would be lost during transmission. Moreover, provirus clones derived from acutely infected MIPs are less susceptible to maraviroc than those from chronically infected MIPs. Conclusions—Our study suggests that the transmission mode of primary resistance mutations and the sensitivity to maraviroc are dependent on infection status of MIPs either acutely or chronically infected. These results may indicate that higher dose of maraviroc could be needed for treatment of acutely infected MIPs compared to chronically infected MIPs

Analysis of primary resistance mutations to HIV-1 entry inhibitors in therapy naive subtype C HIV-1 infected mother– infant pairs from Zambia

Background—Small molecular CCR5 inhibitors represent a new class of drugs for treating HIV-1 infection. The evaluation of the primary resistance mutations associated with entry inhibitors during HIV-1 perinatal transmission is required because they may have a profound impact on the clinical management in MTCT. Objectives—To evaluate the primary resistance mutations to maraviroc and vicriviroc during perinatal transmission and analyze the sensitivity of Env derived from mother–infant pairs to maraviroc. Study design—Nine MIPs infected by subtype C HIV-1 were recruited to analyze the prevalence and transmission of primary resistance mutations to maraviroc and vicriviroc. Moreover, Env derived from six MIPs were employed to construct provirus clones and to analyze the sensitivity to maraviroc. Results—Mutations A316T, conferring partial resistance to maraviroc, T307I and R315Q, both conferring partial resistance to vicriviroc are prevalent in mother and infant cohorts, indicating the transmission of primary resistance mutations during HIV-1 perinatal transmission. However, the mutations of acutely infected mothers seem to directly transmit to their corresponding infants, while some mutations at low frequency of chronically infected mothers would be lost during transmission. Moreover, provirus clones derived from acutely infected MIPs are less susceptible to maraviroc than those from chronically infected MIPs. Conclusions—Our study suggests that the transmission mode of primary resistance mutations and the sensitivity to maraviroc are dependent on infection status of MIPs either acutely or chronically infected. These results may indicate that higher dose of maraviroc could be needed for treatment of acutely infected MIPs compared to chronically infected MIPs

1-Benzyl-3-[3-(naphthalen-2-yl­oxy)prop­yl]imidazolium hexa­fluoro­phosphate

In the title salt, C23H23N2O+·PF6 −, the PF6 − anion is highly disordered (occupancy ratios of 0.35:0.35:0.3, 0.7:0.15:0.15, 0.7:0.3 and 0.35:0.35:0.15:0.15) with the four F atoms in the equatorial plane rotating about the axial F—P—F bond. The mean plane of the imidazole ring makes dihedral angles of 82.44 (17) and 14.39 (16)°, respectively, with the mean planes of the benzene ring and the naphthalene ring system. The crystal structure is stabilized by C—H⋯F hydrogen bonds. In addition, π–π [centroid–centroid distances = 3.7271 (19)–3.8895 (17) Å] and C—H⋯π inter­actions are observed

A possible link between sinusitis and lower airway hypersensitivity: the role of Staphylococcal enterotoxin B

BACKGROUND AND AIMS: The prevalence of asthma has been keeping arising with unknown etiology. The cumulative evidence indicates that chronic rhinosinusitis (CRS) closely relates to asthma, but the detailed mechanisms remain unclear. The present study aimed to take insight into the role of Staphylococcus enterotoxin B (SEB) in a possible association between CRS and asthma. METHODS: 38 patients with both CRS and asthma underwent functional endoscopic sinus surgery. Serum specific IgE and cytokines, clinical symptoms of CRS and asthma were evaluated before and after the surgery. Peripheral blood mononuclear cells (PBMCs) were separated from the patients and cultured. Th2 response of the cultured PBMCs in the presence or absence of specific antigens and SEB was evaluated. RESULTS: Besides the improvement of CRS symptoms, amelioration of asthma was also observed in the patients with both CRS and asthma after the sinus surgery. The preoperatively elevated Th2 cytokines, IL-4 and IL-5, normalized postoperatively. Th2 response was generated with separated PBMCs in the presence of specific antigens. SEB was required for maintaining Th2 response in these separated PBMCs. CONCLUSION: The present results indicate that a possible link exists between CRS and lower airway hypersensitivity. Sinusitis derived SEB may play a role in sustaining Th2 responses in the low airway hypersensitivity related to sinusitis

Implication of cholinergic transmission in rat model of spinal cord injury: A potential therapeutic target

Purpose: To assess the involvement of cholinergic transmission in the etiology of spinal cord injury (SCI) in a rat model. Methods: Male adult rats (Wistar) with body weight ranging from 200 to 250 g were equally allocated into 2 groups: test (SCI) and control (non-SCI). Clipping method was used to induce SCI. Thereafter, motor function was measured using rotarod. Each rat was sacrificed by decapitation, and the cortex was excised for use in the study of the involvement of cholinergic transmission in SCI using real time quantitative polymerase chain reaction (RT-PCR) and western blot analysis (WBA). Results: Significant upregulation in acetylcholine esterase (AChE) was observed in the cortex of SCI rats, relative to non-SCI rats (p < 0.005). Results from cholinergic receptor binding studies revealed significantly decreased maximum binding (Bmax) and dissociation constant (kd) values for muscarinic receptors in SCI rats, when compared to non-SCI rats. Moreover, the reduction in intensity of cholinergic receptors was significantly greater in the cerebral cortex of SCI group compared to non-SCI group. Conclusion: The results of this study suggested that the reduction in cortical cholinergic transmission impairs motor functions in SCI, and plays a major role in motor deficits in SCI

Intraday pair trading strategies on high frequency data: the case of oil companies

This paper introduces novel ‘doubly mean-reverting’ processes based on conditional modelling of model spreads between pairs of stocks. Intraday trading strategies using high frequency data are proposed based on the model. This model framework and the strategies are designed to capture ‘local’ market inefficiencies that are elusive for traditional pairs trading strategies with daily data. Results from real data back-testing for two periods show remarkable returns, even accounting for transaction costs, with annualized Sharpe ratios of 3.9 and 7.2 over the periods June 2013–April 2015 and 2008, respectively. By choosing the particular sector of oil companies, we also confirm the observation that the commodity price is the main driver of the share prices of commodity-producing companies at times of spikes in the related commodity market