Sexual transmission chains of Ebola virus (EBOV) have been verified and linked to EBOV RNA persistence in semen, post-recovery. The rate of semen persistence over time, including the average duration ...of persistence among Ebola virus disease (EVD) survivors, is not well known. This cohort study aimed to analyze population estimates of EBOV RNA persistence rates in semen over time, and associated risk factors in a population of survivors from Sierra Leone.
In this cohort study from May 2015 to April 2017 in Sierra Leone, recruitment was conducted in 2 phases; the first enrolled 100 male participants from the Western Area District in the capital of Freetown, and the second enrolled 120 men from the Western Area District and from Lungi, Port Loko District. Mean age of participants was 31 years. The men provided semen for testing, analyzed by quantitative reverse transcription PCR (qRT-PCR) for the presence of EBOV RNA. Follow-up occurred every 2 weeks until the endpoint, defined as 2 consecutive negative qRT-PCR results of semen specimen testing for EBOV RNA. Participants were matched with the Sierra Leone EVD case database to retrieve cycle threshold (Ct) values from the qRT-PCR analysis done in blood during acute disease. A purposive sampling strategy was used, and the included sample composition was compared to the national EVD survivor database to understand deviations from the general male survivor population. At 180 days (6 months) after Ebola treatment unit (ETU) discharge, the EBOV RNA semen positive rate was 75.4% (95% CI 66.9%-82.0%). The median persistence duration was 204 days, with 50% of men having cleared their semen of EBOV RNA after this time. At 270 days, persistence was 26.8% (95% CI 20.0%-34.2%), and at 360 days, 6.0% (95% CI 3.1%-10.2%). Longer persistence was significantly associated with severe acute disease, with probability of persistence in this population at 1 year at 10.1% (95% CI 4.6%-19.8%) compared to the probability approaching 0% for those with mild acute disease. Age showed a dose-response pattern, where the youngest men (≤25 years) were 3.17 (95% CI 1.60, 6.29) times more likely to be EBOV RNA negative in semen, and men aged 26-35 years were 1.85 (95% CI 1.04, 3.28) times more likely to be negative, than men aged >35 years. Among participants with both severe acute EVD and a higher age (>35 years), persistence remained above 20% (95% CI 6.0%-50.6%) at 1 year. Uptake of safe sex recommendations 3 months after ETU discharge was low among a third of survivors. The sample was largely representative of male survivors in Sierra Leone. A limitation of this study is the lack of knowledge about infectiousness.
In this study we observed that EBOV RNA persistence in semen was a frequent phenomenon, with high population rates over time. This finding will inform forthcoming updated recommendations on risk reduction strategies relating to sexual transmission of EBOV. Our findings support implementation of a semen testing program as part of epidemic preparedness and response. Further, the results will enable planning of the magnitude of testing and targeted counseling needs over time.
The accumulation of myeloid-derived suppressor cells (MDSCs) has been observed in solid tumors and is correlated with tumor progression; however, the underlying mechanism is still poorly understood. ...In this study, we identified a mechanism by which tumor cells induce MDSC accumulation and expansion in the bladder cancer (BC) microenvironment via CXCL2/MIF-CXCR2 signaling. Elevated expression of CXCL2 and MIF and an increased number of CD33
MDSCs were detected in BC tissues, and these increases were significantly associated with advanced disease stage and poor patient prognosis (P<0.01). A positive association was observed between CXCL2 or MIF expression and the number of tumor-infiltrating CD33
MDSCs (P<0.01). Subsequently, we demonstrated that CD45
CD33
CD11b
HLA-DR
MDSCs from fresh BC tissues displayed high levels of suppressive molecules, including Arg1, iNOS, ROS, PDL-1 and P-STAT3, and stronger suppression of T-cell proliferation. Interestingly, these CD45
CD33
CD11b
HLA-DR
MDSCs exhibited increased CXCR2 expression compared with that in peripheral blood from BC patients or healthy controls (P<0.05). Chemotaxis assay revealed that bladder cancer cell line J82 induced MDSC migration via CXCL2/MIF-CXCR2 signaling in vitro. Mechanistic studies demonstrated that J82-induced MDSC trafficking and CXCR2 expression were associated with increased phosphorylation of p38, ERK and p65. Conversely, inhibition of the phosphorylation of p38, ERK or p65 decreased J82-induced MDSC trafficking and CXCR2 expression. CXCL2/MIF-stimulated activation of the mitogen-activated protein kinase and nuclear factor kappa B pathways in MDSCs was MyD88 dependent. Overall, our results identify the CXCL2/MIF-CXCR2 axis as an important mediator in MDSC recruitment and as predictors and potential therapeutic targets in BC patients.
A chemical genetic roadmap to improved tomato flavor Tieman, Denise; Zhu, Guangtao; Resende, Marcio F. R. ...
Science (American Association for the Advancement of Science),
01/2017, Letnik:
355, Številka:
6323
Journal Article
Recenzirano
Modern commercial tomato varieties are substantially less flavorful than heirloom varieties. To understand and ultimately correct this deficiency, we quantified flavor-associated chemicals in 398 ...modern, heirloom, and wild accessions. A subset of these accessions was evaluated in consumer panels, identifying the chemicals that made the most important contributions to flavor and consumer liking. We found that modern commercial varieties contain significantly lower amounts of many of these important flavor chemicals than older varieties. Whole-genome sequencing and a genome-wide association study permitted identification of genetic loci that affect most of the target flavor chemicals, including sugars, acids, and volatiles. Together, these results provide an understanding of the flavor deficiencies in modern commercial varieties and the information necessary for the recovery of good flavor through molecular breeding.
Using a novel method of isochronous mass spectrometry, the masses of ^{62}Ge, ^{64}As, ^{66}Se, and ^{70}Kr are measured for the first time, and the masses of ^{58}Zn, ^{61}Ga, ^{63}Ge, ^{65}As, ...^{67}Se, ^{71}Kr, and ^{75}Sr are redetermined with improved accuracy. The new masses allow us to derive residual proton-neutron interactions (δV_{pn}) in the N=Z nuclei, which are found to decrease (increase) with increasing mass A for even-even (odd-odd) nuclei beyond Z=28. This bifurcation of δV_{pn} cannot be reproduced by the available mass models, nor is it consistent with expectations of a pseudo-SU(4) symmetry restoration in the fp shell. We performed ab initio calculations with a chiral three-nucleon force (3NF) included, which indicate the enhancement of the T=1 pn pairing over the T=0 pn pairing in this mass region, leading to the opposite evolving trends of δV_{pn} in even-even and odd-odd nuclei.
Aim
Gastroparesis is a common non‐motor system symptom of Parkinson's disease (PD). However, the mechanism responsible for the gastric motor abnormality is not clear. We previously reported on the ...impaired gastric motility in 6‐hydroxydopamine (6‐OHDA) rats, which were treated with a bilateral microinjection of 6‐OHDA in the substantia nigra (SN). We hypothesize that the enhanced dopamine system and reduced acetylcholine (Ach) in gastric tissues might contribute to the delayed gastric emptying observed in PD.
Methods
A strain gauge force transducer, digital X‐ray imaging system, Western blot, immunofluorescence and Radio Immunoassay were used in this study.
Results
Dopaminergic neurones in the SN were greatly reduced following the bilateral microinjection of 6‐OHDA. 6‐OHDA rats exhibited impaired gastric motility and delayed gastric emptying, accompanied by increased dopamine content and the overexpression of D2 receptors in the stomach. The administration of the D2 receptor antagonist domperidone relieved gastric dysmotility in 6‐OHDA rats, but the D1 receptor antagonist SCH23390 failed to do so. Subdiaphragmatic vagotomy prevented the increase in the gastric dopamine content and D2 receptor expression and improved gastric dysmotility in 6‐OHDA rats.
Conclusion
Dopaminergic deficiency in the SN results in impaired gastric motility, possibly as a result of the enhanced activity of dopamine system and reduced Ach in gastric tissue. The vagus nerve plays an important role in peripheral gastric motility disorder.
Dapsone is an important medication for the treatment of leprosy, but a life-threatening drug hypersensitivity syndrome develops in some patients. In this report from China, an
HLA-B
locus is ...identified as a strong genetic risk factor for the syndrome.
Dapsone (4-4′-sulfonyldianiline), which was first synthesized in 1908,
1
is both an antibiotic and an antiinflammatory agent. Dapsone alone or in combination with other drugs has been used for the prevention and treatment of infectious diseases (e.g., leprosy, malaria, and actinomycetoma, as well as
Pneumocystis jirovecii
pneumonia in persons with human immunodeficiency virus HIV infection) and chronic inflammatory diseases characterized by the infiltration of neutrophils or eosinophils (e.g., dermatitis herpetiformis, linear IgA dermatosis, subcorneal pustular dermatosis, and erythema elevatum diutinum).
2
,
3
About 0.5 to 3.6% of persons treated with dapsone have a drug hypersensitivity syndrome,
3
–
5
which was first described by . . .
In a neutral solution, coating formation by micro-arc oxidation (MAO) on AZ91HP magnesium alloy was studied. The process involved the substrate dissolution and coating development. During the first 5
...s, the sample mass decreased, indicating substrate dissolution dominating the process. After 5
s, the sample mass began to increase and the coating development began to predominate the process. The coating was firstly nucleated on α phase and sparks initially appeared mainly on the edges of the sample. With treating proceeded, the coating was becoming uniform; meanwhile, microscopic pores of anodic coatings increased in size and decreased in number.
Pain inhibition by additional somatosensory input is the rationale for the widespread use of Transcutaneous Electrical Nerve Stimulation (TENS) to relieve pain. Two main types of TENS produce ...analgesia in animal models: high-frequency (∼50–100 Hz) and low-intensity ‘conventional’ TENS, and low-frequency (∼2–4 Hz) and high-intensity ‘acupuncture-like’ TENS. However, TENS efficacy in human participants is debated, raising the question of whether the analgesic mechanisms identified in animal models are valid in humans. Here, we used a sham-controlled experimental design to clarify the efficacy and the neurobiological effects of ‘conventional’ and ‘acupuncture-like’ TENS in 80 human volunteers. To test the analgesic effect of TENS we recorded the perceptual and brain responses elicited by radiant heat laser pulses that activate selectively Aδ and C cutaneous nociceptors. To test whether TENS has a long-lasting effect on brain state we recorded spontaneous electrocortical oscillations. The analgesic effect of ‘conventional’ TENS was maximal when nociceptive stimuli were delivered homotopically, to the same hand that received the TENS. In contrast, ‘acupuncture-like’ TENS produced a spatially-diffuse analgesic effect, coupled with long-lasting changes both in the state of the primary sensorimotor cortex (S1/M1) and in the functional connectivity between S1/M1 and the medial prefrontal cortex, a core region in the descending pain inhibitory system. These results demonstrate that ‘conventional’ and ‘acupuncture-like’ TENS have different analgesic effects, which are mediated by different neurobiological mechanisms.
•‘Acupuncture-like’ TENS produces a spatially-diffuse analgesic effect.•‘Conventional’ TENS produces a spatially-localized analgesic effect.•‘Acupuncture-like’ TENS results in an enhancement of ongoing α oscillation in S1/M1.•‘Acupuncture-like’ TENS results in an enhanced connectivity between S1/M1 and mPFC.•These two types of TENS are mediated by different neurobiological mechanisms.
Single nucleotide polymorphisms (SNPs) near the IL28B gene have been shown to be associated with response to treatment for chronic hepatitis C and also with spontaneous clearance of hepatitis C virus ...(HCV) infection. We analysed the association between IL28B genetic variants and spontaneous clearance of HCV infection in 376 HCV‐infected Chinese paid plasma donors. Genotyping of eight SNPs near the IL28B region was performed by the iPLEX system (MassARRAY® SNP Genotyping; Sequenom) in all donors, and sequencing was performed on all 80 donors who cleared HCV and on 160 of 296 donors who did not clear HCV to validate the genotypes. Eighty (21.3%) donors spontaneously cleared HCV. Four SNPs were significantly associated with spontaneous HCV clearance: rs8099917 TT (vs GT), rs8105790 TT (vs CT), rs12980275 AA (vs AG) and rs10853728 CC (vs CG or GG) with OR (95% CI) 15.27 (2.07–112.50), 14.88 (2.02–109.72), 7.92 (1.88–33.32) and 2.32 (1.22–4.42) respectively. No association between the other four IL28B SNPs including rs12979860 and spontaneous HCV clearance was found. Women had a higher rate of spontaneous HCV clearance than men 56/213 (26.3%) vs 24/163 (14.6%), P = 0.007, and this was true even after stratification for IL28B genotypes with OR of 1.9–2.2 among those with favourable genotypes. Our results confirmed that IL28B polymorphism is associated with spontaneous clearance of HCV in Chinese subjects, but the SNPs that predict HCV clearance in Chinese subjects were different from those reported in Caucasians. Women were more likely to clear HCV infection regardless of IL28B genotypes.
Abstract Objective Multi-mode universal adhesives offer clinicians the choice of using the etch-and-rinse technique, selective enamel etch technique or self-etch technique to bond to tooth ...substrates. The present study examined the short-term in vitro performance of five universal adhesives bonded to human coronal dentine. Methods Two hundred non-carious human third molars were assigned to five groups based on the type of the universal adhesives (Prime&Bond Elect, Scotchbond Universal, All-Bond Universal, Clearfil Universal Bond and Futurabond U). Two bonding modes (etch-and-rinse and self-etch) were employed for each adhesive group. Bonded specimens were stored in deionized water for 24 h or underwent a 10,000-cycle thermocycling ageing process prior to testing ( N = 10). Microtensile bond testing (μTBS), transmission electron microscopy (TEM) of resin–dentine interfaces in non-thermocycled specimens and scanning electron microscopy (SEM) of tracer-infused water-rich zones within hybrid layers of thermocycled specimens were performed. Results Both adhesive type and testing condition (with/without thermocycling) have significant influences on μTBS. The use of each adhesive in either the etch-and-rinse or self-etch application mode did not result in significantly different μTBS to dentine. Hybrid layers created by these adhesives in the etch-and-rinse bonding mode and self-etch bonding mode were ∼5 μm and ≤0.5 μm thick respectively. Tracer-infused regions could be identified within the resin–dentine interface from all the specimens prepared. Conclusion The increase in versatility of universal adhesives is not accompanied by technological advances for overcoming the challenges associated with previous generations of adhesives. Therapeutic adhesives with bio-protective and bio-promoting effects are still lacking in commercialized adhesives. Clinical significance Universal adhesives represent manufacturers’ attempt to introduce versatility in product design via adaptation of a single-bottle self-etch adhesive for other application modes without compromising its bonding effectiveness.
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