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Human immunodeficiency virus type-1 (HIV-1) causes a spectrum of neurological impairments, termed HIV-associated neurocognitive disorder (HAND), following the infiltration of infected cells into the brain. Even though the implementation of antiretroviral therapy reduced the systemic viral load, the prevalence of HAND remains unchanged and infected patients develop persisting neurological disturbances affecting their quality of life. As a result, HAND have gained importance in basic and clinical researches, warranting the need of developing new adjunctive treatments. Nonetheless, a better understanding of the molecular and cellular mechanisms remains necessary. Several studies consolidated their efforts into elucidating the neurotoxic signaling leading to HAND including the deleterious actions of HIV-1 viral proteins and inflammatory mediators. However, the scope of these studies is not sufficient to address all the complexity related to HAND development. Fewer studies focused on an altered neuroprotective capacity of the brain to respond to HIV-1 infection. Neurotrophic factors are endogenous polyproteins involved in neuronal survival, synaptic plasticity, and neurogenesis. Any defects in the processing or production of these crucial factors might compose a risk factor rendering the brain more vulnerable to neuronal damages. Due to their essential roles, they have been investigated for their diverse interplays with HIV-1 infection. In this review, we present a complete description of the neurotrophic factors involved in HAND. We discuss emerging concepts for their therapeutic applications and summarize the complex mechanisms that down-regulate their production in favor of a neurotoxic environment. For certain factors, we finally address opposing roles that rather lead to increased inflammation.Immunochips containing 12 recombinant antigens of T. pallidum (Тр15, Тр17, Тр47, TmpA, Тр0163, Тр0277, Тр0319, Тр0453, Тр0684, Тр0965, Тр0971, and Тр1038) were prepared to assay for IgG and IgM in serum samples (n=68) of healthy individuals and patients with the latent stages of syphilis. The linear discriminant analysis of detected IgG and IgM differentiated three groups of serum samples as 1) early latent syphilis; 2) seroresistant early latent syphilis; and 3) late latent syphilis with overall differentiation potency of 95.6% (88.9-100%). The samples of all syphilis patients were differentiated from the samples of healthy individuals with 100% specificity.
Bakanae is a seedborne disease caused by Fusarium fujikuroi. Rice seedlings emerging from infected seeds can show diverse symptoms such as elongated and slender stem and leaves, pale coloring, a large leaf angle, stunted growth and even death. Little is known about rice defense mechanisms at early stages of disease development.
This study focused on investigating early defenses against F. fujikuroi in a susceptible cultivar, Zerawchanica karatals (ZK), and a resistant cultivar, Tainung 67 (TNG67). Quantitative PCR revealed that F. check details fujikuroi colonizes the root and stem but not leaf tissues. Illumina sequencing was conducted to analyze the stem transcriptomes of F. fujikuroi-inoculated and mock-inoculated ZK and TNG67 plants collected at 7 days post inoculation (dpi). More differentially expressed genes (DEGs) were identified in ZK (n = 169) than TNG67 (n = 118), and gene ontology terms related to transcription factor activity and phosphorylation were specifically enriched in ZK DEGs. Among the complex phyt
Cerebrospinal fluid (CSF) has emerged as a sensitive matrix for the screening of biomarkers for diagnosis and clinical follow-up of diseases with neurological manifestations, including some lysosomal storage disorders. In this study, we assessed the range of values of arylsulfatase A (ARSA) activity in the CSF of pediatric and adult donors, and in pediatric patients who underwent gene therapy for metachromatic leukodystrophy (MLD).
A cohort of 56 CSF samples was included in the study pediatric donors (n = 36), adult donors (n = 9), and MLD patients (n = 11) at different timepoints [pre-gene therapy (GT), post-GT + 1 Year, post-GT + 2 Years, post-GT + 3 Years]. We have used our fluorometric assay for the determination of ARSA activity. The total protein content in the samples was also evaluated.
We discovered that ARSA activity was higher in pediatric donors (geometric mean 1.039 nmol/mg/h; 95% range 0.859-1.258 nmol/mg/h) compared to adults (geometric mean 0.305 nmol/mg/h; 95% range 0.214-0.435 nmol/mg/h). No ARSA activity was detected in the CSF of MLD patients pre-GT, whereas ARSA activity was stably expressed and almost restored to range of values of pediatric donors in MLD patients post-GT + 3 Years with a geometric mean of 0.822 nmol/mg/h (95% range 0.580-1.165 nmol/mg/h).
This study establishes range of values of ARSA activity in the CSF for MLD clinical practice. The observed ranges of ARSA activities in CSF exhibited an unpredicted age dependence and, in turn, revealed the need of using pediatric ARSA activity for evaluating the restoration of the enzyme activity during the therapy of MLD.
This study establishes range of values of ARSA activity in the CSF for MLD clinical practice. The observed ranges of ARSA activities in CSF exhibited an unpredicted age dependence and, in turn, revealed the need of using pediatric ARSA activity for evaluating the restoration of the enzyme activity during the therapy of MLD.
Antiretroviral treatment (ART) during acute/recent HIV infection decreases transmission and optimizes immune recovery but the optimal ART-regimen in this setting is unknown. The objectives were to analyze the virological efficacy, immunological reconstitution and tolerability of different ART-regimens at 3 years after starting ART during acute/recent HIV infection.
Retrospective cohort study of consecutive acutely/recently infected patients who started ART within 6 months postinfection.
We compared regimens based on protease-inhibitors (N = 28), integrase-strand-transfer-inhibitors (InSTI, N = 87) and nonnucleoside-reverse-transcriptase-inhibitors (N = 22). Virological suppression (viral load <50 copies/ml), immune reconstitution (CD4 T-cell count >900 cells/μl and CD4/CD8 ratio >1) and adverse events leading to ART discontinuation at 1 and 3 years were compared.
Baseline characteristics were comparable among groups. Overall viral suppression at 1 (96%) and 3 years (99%) was comparable in aller proportion of long-term immunological recovery.Hypertension is a chronic condition leading to increased stress on the heart and blood vessels, a critical risk factor for clinically significant events such as myocardial infarction heart failure, stroke and death. Chlorthalidone and hydrochlorothiazide are first-line antihypertensive agents for most patients with hypertension. The aim of our meta-analysis was to compare the efficacy and safety of both therapies in patients with hypertension. Searches of electronic databases PubMed, MEDLINE, Scopus, PsycInfo and eLIBRARY.ru, were performed. We used network meta-analysis to combine direct and indirect evidence. Forest plots and closed loops depict estimated results from studies included in our meta-analysis. Of 1289 identified sources, only 37 were included in our meta-analysis. Our analysis has demonstrated a slight superiority for chlorthalidone regarding SBP and not statistically significant differences regarding DBP. Simultaneously, hydrochlorothiazide seems to be a safer choice of therapy, as evidenced by the levels of serum potassium. The two diuretics can be used interchangeably.
The purpose of this meta-analysis was to evaluate the effects of vitamin D supplementation on metabolic parameters of women with polycystic ovary syndrome (PCOS).
We performed a literature search of databases and identified randomized controlled trials (RCTs) published prior to December 2019. A meta-analysis was conducted using RevMan 5.3 and Stata 12.0 software. We compared the effects of vitamin D supplementation alone to the administration of placebos on metabolic parameters of PCOS women with vitamin D deficiency.
Ten articles of RCTs were included and analyzed in this meta-analysis, which included a total of 520 PCOS women. Our meta-analysis results showed no significant effects of vitamin D supplementation on BMI (
= .43), systolic blood pressure (
= .05), diastolic blood pressure (
= .87), fasting insulin concentration (
= .86), HOMA-IR (
= .47), HDL-C (
= .76), LDL-C (
= .23) and triglyceride (
= .77). Both low dose vitamin D supplementation (<4000 IU/day) and high dose vitamin D supplementation (≥4000 IU/day) were found to significantly decreased the fasting glucose concentration (
= .01,
= .001, respectively). Vitamin D supplementation significantly decreased total cholesterol concentration (
= .03).
The results of this meta-analysis suggested that vitamin D supplementation decreases fasting glucose concentration and total cholesterol concentration in PCOS women with vitamin D deficiency.
The results of this meta-analysis suggested that vitamin D supplementation decreases fasting glucose concentration and total cholesterol concentration in PCOS women with vitamin D deficiency.Irradiation of a molecular system by an intense laser field can trigger dynamics of both electronic and nuclear subsystems. The lighter electrons usually move on much faster, attosecond timescale but the slow nuclear rearrangement damps ultrafast electronic oscillations, leading to the decoherence of the electronic dynamics within a few femtoseconds. We show that a simple, single-trajectory semiclassical scheme can evaluate the electronic coherence time in polyatomic molecules accurately by demonstrating an excellent agreement with full-dimensional quantum calculations. In contrast to numerical quantum methods, the semiclassical one reveals the physical mechanism of decoherence beyond the general blame on nuclear motion. In the propiolic acid, the rate of decoherence and the large deviation from the static frequency of electronic oscillations are quantitatively described with just two semiclassical parameters-the phase space distance and signed area between the trajectories moving on two electronic surfaces. Because it evaluates the electronic structure on the fly, the semiclassical technique avoids the "curse of dimensionality" and should be useful for preselecting molecules for experimental studies.
Inadequate myelosuppression during maintenance therapy for acute lymphoblastic leukemia (ALL) is associated with an increased risk of relapse. One mechanism is skewed metabolism of 6-mercaptopurine (6MP), a major component of maintenance therapy, which results in preferential formation of the hepatotoxic metabolite (6-methyl mercaptopurine [6MMP]) with low levels of the antileukemic metabolite, 6-thioguanine nucleotides (6TGN). Allopurinol can modify 6MP metabolism to favor 6TGN production and reduce 6MMP.
Patients in maintenance were considered for allopurinol treatment who had the following features (a) Grade≥3 hepatotoxicity; (b) Grade≥2 nonhepatic gastrointestinal (GI) toxicity; or (c) persistently elevated absolute neutrophil count (ANC) despite >150% protocol dosing of oral chemotherapy.
From 2013 to 2017, 13 ALL patients received allopurinol nine for hepatotoxicity, five for inadequate myelosuppression, and three for nonhepatic GI toxicity (four met multiple criteria). Allopurinol was well tolerated, without significant adverse events.
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