402 research outputs found

    Host genetics and viral load in primary HIV-1 infection: clear evidence for gene by sex interactions

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    © 2014, The Author(s).Research in the past two decades has generated unequivocal evidence that host genetic variations substantially account for the heterogeneous outcomes following human immunodeficiency virus type 1 (HIV-1) infection. In particular, genes encoding human leukocyte antigens (HLA) have various alleles, haplotypes, or specific motifs that can dictate the set-point (a relatively steady state) of plasma viral load (VL), although rapid viral evolution driven by innate and acquired immune responses can obscure the long-term relationships between HLA genotypes and HIV-1-related outcomes. In our analyses of VL data from 521 recent HIV-1 seroconverters enrolled from eastern and southern Africa, HLA-A*03:01 was strongly and persistently associated with low VL in women (frequency = 11.3 %, P  0.50). In a reduced multivariable model, age, sex, geography (clinical sites), previously identified HLA factors (HLA-B*18, B*45, B*53, and B*57), and the interaction term for female sex and HLA-A*03:01 collectively explained 17.0 % of the overall variance in geometric mean VL over a 3-year follow-up period (P < 0.0001). Multiple sensitivity analyses of longitudinal and cross-sectional VL data yielded consistent results. These findings can serve as a proof of principle that the gap of “missing heritability” in quantitative genetics can be partially bridged by a systematic evaluation of sex-specific associations

    Peran Kepuasan Pelanggan dalam Memediasi Pengaruh Kualitas Produk terhadap Loyalitas Pelanggan pada Produk Pewangi Pakaian Molto di Kota Denpasar

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    Penelitian ini dilakukan untuk mengetahui peran kepuasan pelanggan dalam memediasi pengaruh kualitas produk terhadap loyalitas pelanggan produk pewangi pakaian Molto di Kota Denpasar. Desain penelitian menggunakan metode asosiatif yang berbentuk kausal (sebab akibat). Sampel yang digunakan berjumlah 100 responden.Teknik pengumpulan data yang digunakan adalah menyebarkan kuesioner kepada para pelanggan produk pewangi pakaian Molto di Kota Denpasar. Metode analisis data menggunakan analisis jalur (path analysis) yang disertai Uji Sobel untuk menguji hubungan mediasi antar variabel. Hasil penelitian menyatakan peran kepuasan pelanggan mampu memediasi secara positif dan signifikan pengaruh kualitas produk terhadap loyalitas pelanggan produk pewangi pakaian Molto di Kota Denpasar

    Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

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    © 2015 Elsevier Inc.Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies

    EEG Artifact Removal in TMS Studies of Cortical Speech Areas

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    The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is commonly applied for studying the effective connectivity of neuronal circuits. The stimulation excites neurons, and the resulting TMS-evoked potentials (TEPs) are recorded with EEG. A serious obstacle in this method is the generation of large muscle artifacts from scalp muscles, especially when frontolateral and temporoparietal, such as speech, areas are stimulated. Here, TMS–EEG data were processed with the signal-space projection and source-informed reconstruction (SSP–SIR) artifact-removal methods to suppress these artifacts. SSP–SIR suppressed muscle artifacts according to the difference in frequency contents of neuronal signals and muscle activity. The effectiveness of SSP–SIR in rejecting muscle artifacts and the degree of excessive attenuation of brain EEG signals were investigated by comparing the processed versions of the recorded TMS–EEG data with simulated data. The calculated individual lead-field matrix describing how the brain signals spread on the cortex were used as simulated data. We conclude that SSP–SIR was effective in suppressing artifacts also when frontolateral and temporoparietal cortical sites were stimulated, but it may have suppressed also the brain signals near the stimulation site. Effective connectivity originating from the speech-related areas may be studied even when speech areas are stimulated at least on the contralateral hemisphere where the signals were not suppressed that much.Peer reviewe

    HIV disease progression compared by linkage status in Rwanda and Zambia

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    The effect of experimental pain on short-interval intracortical inhibition with multi-locus transcranial magnetic stimulation

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    Chronic neuropathic pain is known to alter the primary motor cortex (M1) function. Less is known about the normal, physiological effects of experimental neurogenic pain on M1. The objective of this study is to determine how short-interval intracortical inhibition (SICI) is altered in the M1 representation area of a muscle exposed to experimental pain compared to SICI of another muscle not exposed to pain. The cortical representation areas of the right abductor pollicis brevis (APB) and biceps brachii (BB) muscles of 11 subjects were stimulated with a multi-locus transcranial magnetic stimulation device while the resulting motor-evoked potentials (MEPs) were recorded with electromyography. Single- and paired-pulse TMS was administered in seven conditions, including one with the right hand placed in cold water. The stimulation intensity for the conditioning pulses in the paired-pulse examination was 80% of the resting motor threshold (RMT) of the stimulated site and 120% of RMT for both the test and single pulses. The paired-pulse MEP amplitudes were normalized with the mean amplitude of the single-pulse MEPs of the same condition and muscle. SICI was compared between conditions. After the cold pain, the normalized paired-pulse MEP amplitudes decreased in APB, but not in BB, indicating that SICI was potentially increased only in the cortical area of the muscle subjected to pain. These data suggest that SICI is increased in the M1 representation area of a hand muscle shortly after exposure to pain has ended, which implies that short-lasting pain can alter the inhibitory balance in M1.Peer reviewe

    LIGHT AND ELECTRON MICROSCOPIC STUDY OF SURFACES OF TEST-SPECIMENS TESTED IN WEAR APPARATUSES

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    Objective: Symptoms of acute retroviral syndrome (ARS) may be used to identify patients with acute HIV-1 infection who seek care. ARS symptoms in African adults differ by region. We assessed whether reporting of ARS was associated with HIV-1 subtype in a multicentre African cohort study representing countries with predominant HIV-1 subtypes A, C, and D. Methods: ARS symptoms were assessed in adults enrolling within 6 weeks after the estimated date of infection in an acute and early HIV-1 infection cohort study. HIV-1 subtype was determined by POL genotyping. We used log-binomial regression to compare ARS symptom prevalence among those with subtype A vs. C or D, adjusting for sex, time since enrolment, and enrolment viral load. Results: Among 183 volunteers ascertained within 6 weeks after estimated date of infection, 77 (42.0%) had subtype A, 83 (45.4%) subtype C, and 23 (12.6%) subtype D infection. Individuals with subtype A were 1.40 (95% confidence interval: 1.17, 1.68) times as likely as individuals with subtypes C or D to report any ARS symptoms; each individual symptom other than rash was also more prevalent in subtype A than in subtype C or D, with prevalence ratios ranging from 1.94 (1.40, 2.70) for headache to 4.92 (2.24, 10.78) for lymphadenopathy. Conclusion: Individuals with subtype A were significantly more likely than individuals with subtypes C or D to report any ARS symptoms. HIV-1 subtypes may help explain differences in ARS that have been observed across regions in Africa, and may impact the yield of symptom-based screening strategies for acute HIV infection detection
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