Telomere length inversely correlates with pulse pressure and is highly familial

There is evidence that telomeres, the ends of chromosomes, serve as clocks that pace cellular aging in vitro and in vivo. In industrialized nations, pulse pressure rises with age, and it might serve as a phenotype of biological aging of the vasculature. We therefore conducted a twin study to investigate the relation between telomere length in white blood cells and pulse pressure while simultaneously assessing the role of genetic factors in determining telomere length. We measured by Southern blot analysis the mean length of the terminal restriction fragments (TRF) in white blood cells of 49 twin pairs from the Danish Twin Register and assessed the relations of blood pressure parameters with TRF. TRF length showed an inverse relation with pulse pressure. Both TRF length and pulse pressure were highly familial. We conclude that telomere length, which is under genetic control, might play a role in mechanisms that regulate pulse pressure, including vascular aging.     

Chlorhexidine in Dentistry: Pharmacology,Uses, and Adverse Effects

ObjectivesThe aim of this work was to review the current uses of chlorhexidine (CHX) in dentistry based on its mechanism of action, whilst highlighting the most effective protocols that render the highest clinical efficacy whilst limiting adverse drug reactions.MethodsA literature search was conducted using the key words chlorhexidine, mechanism of action, adverse effects, and dentistry using databases in the University of Toronto library system. The titles and abstracts were read, and relevant articles were selected.ResultsA total of 1100 publications were identified, 100 were investigated, and 67 of them were used. Out of the 67 selected articles, 12 were reviews on CHX; 5 articles focussed on CHX gels; 13 focussed on CHX mouthwashes; 8 focussed on CHX products; 13 discussed adverse effects associated with CHX; 13 focussed on periodontal pathology and treatment; 6 focussed on implant periodontal and dental surgeries; 7 evaluated effects on caries; 6 looked at the mechanisms of action; and 12 focussed on the antibacterial and antimicrobial impact on the oral biome. There were multiple areas of overlap amongst the articles, and results showed that CHX provides different uses, but mainly as an adjunct to various treatments. Mouthwash was the most superior medium when used in short time spans when mechanical prophylaxis was not possible for the prevention of gingivitis and maintenance of oral hygiene. CHX products are often used in periodontics, post–oral surgical procedures, and as a prophylaxis for multiple invasive procedures with minimal adverse effects. Tooth staining was the most negative adverse effect reported by patients.ConclusionsCHX's antimicrobial properties make it an ideal prophylactic when mechanical debridement is not possible. CHX mouthwash appears to be more effective compared to gels. Concentrations of 0.12% to 0.2% are recommended; any mouthwash with concentrations above 0.2% will unnecessarily increase the unwanted side effects. CHX is useful amongst various areas of dentistry including oral surgery, periodontics, and even general dentistry. For long-term treatments, especially in periodontitis patients (stage I-III) undergoing nonsurgical treatments, CHX chips are recommended. CHX chips are also recommended as an adjunct to implant debridement in patients with peri-implant mucositis and peri-implantitis over CHX mouthwash and gels.     

Calcium chelation improves spatial learning and synaptic plasticity in aged rats

Impaired regulation of intracellular calcium is thought to adversely affect synaptic plasticity and cognition in the aged brain. Comparing young (2-3 months) and aged (23-26 months) Fisher 344 rats, stratum radiatum-evoked CA1 field EPSPs were smaller and long-term potentiation (LTP) was diminished in aged hippocampal slices. Resting calcium, in presynaptic axonal terminals in the CA1 stratum radiatum area, was elevated in aged slices. Loading the slice with the calcium chelator, BAPTA-AM, depressed LTP in young slices, but enhanced this plasticity in old slices. Forty-five minutes following LTP-inducing high frequency stimulation, resting calcium levels were significantly increased in both young and old presynaptic terminals, and significantly reduced by pretreatment with BAPTA-AM. In vivo, intraperitoneal administration of BAPTA-AM prior to training in the reference memory version of the Morris water maze test, significantly improved the acquisition of spatial learning in aged animals, without a significant effect in young rats. These results support the hypothesis that increasing intracellular neuronal buffering power for calcium in aged rats ameliorates age-related impaired synaptic plasticity and learning.     

A new cryptic virus belonging to the family Partitiviridae was found in watermelon co-infected with Melon necrotic spot virus

A novel virus was detected in watermelon plants (Citrullus lanatus Thunb.) infected with Melon necrotic spot virus (MNSV) using SOLiD next-generation sequence analysis. In addition to the expected MSNV genome, two double-stranded RNA (dsRNA) segments of 1,312 and 1,118 bp were also identified and sequenced from the purified virus preparations. These two dsRNA segments encode two putative partitivirus-related proteins, an RNA-dependent RNA polymerase (RdRP) and a capsid protein, which were sequenced. Genomic-sequence analysis and analysis of phylogenetic relationships indicate that these two dsRNAs together make up the genome of a novel Partitivirus. This virus was found to be closely related to the Pepper cryptic virus 1 and Raphanus sativus cryptic virus. It is suggested that this novel virus putatively named Citrullus lanatus cryptic virus be considered as a new member of the family Partitiviridae.     

Early stroke detection and extent: impact of experience and the role of computed tomography angiography source images

AIM: To test the performance of computed tomography angiography "source images" (CTA-SI) versus unenhanced CT (NCCT) for stroke detection and extent using the Alberta Stroke Programme Early CT Score (ASPECTS), and examine the effect of experience and clinical history. MATERIALS AND METHODS: Studies of 23 consecutive patients presenting within 4.5h were analysed by three reviewers of varying experience. Each reviewer, blinded to clinical information reviewed a random order of NCCT and CTA-SI and documented side of infarct and the ASPECTS. The readings were repeated for CTA-SI with and without clinical information. Performance measures and observer agreement were calculated. Applying an ASPECTS threshold of相似文献   

Age dependent aneuploidy and telomere length of the human vascular endothelium.

RATIONALE: Aneuploidy and telomere length are two major parameters that have been associated with cellular senescence in vitro. In order to explore the role of aneuploidy and telomere length in aging of the human vasculature, we studied these two parameters in direct preparations of endothelial cells of the human abdominal aorta. METHODS: Using fluorescent in situ hybridization on 'touch prep' slides, we evaluated aneuploidy of two autosomes (chromosomes 6 and 16) and sex chromosomes in non cultured endothelial cells of the abdominal aorta as a function of the donor's age. RESULTS: We found that the frequency of aneuploidy of vascular endothelial cells significantly increased with age. This was expressed by age-dependent tetrasomy (r(s)=0.56, P=0.006 for chromosome 6; and r(s)=0.54, P=0.008 for chromosome 16), and age dependent loss of the Y chromosome (r(s)=0.85, P=0.0003). In addition, we found that telomere length was inversely correlated with age (r=-0.38, P=0.008). DATA INTERPRETATION: These findings suggest that indicators of cellular senescence, earlier observed in vitro, are also expressed in the human vascular endothelium in vivo. Aneuploidy and telomere attrition might thus play a role in the aging of the human vasculature.     

Reduced prepulse inhibition is associated with increased hypnotizability

Hypnosis involves the manipulation of conscious attentional discrimination. The prepulse inhibition (PPI) paradigm assesses primary unconscious information processing. We investigated the correlation between hypnotizability and PPI of the startle reflex. Forty-eight healthy subjects were evaluated with the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) and acoustic PPI. Subjects were divided into low, medium, and high hypnotizable groups. The low-hypnotizable group showed a significantly higher inhibition of the startle response, at lead intervals 60 ms and 120 ms, than did the medium- and high-hypnotizable groups. We conclude that hypnotizability and PPI may be negatively correlated. These findings lend further support for the role of dopaminergic neurotransmission mechanisms in the determination of hypnotizability levels.     

Safety and efficacy of AK0529 in respiratory syncytial virus-infected infant patients: A phase 2 proof-of-concept trial

Background

Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available.

Methods

This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1–24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment.

Results

No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A −4.0 (95% CI: −4.51, −2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with −2.0 (95% CI: −3.42, −1.82) in the placebo group.

Conclusions

AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score.

Clinical Trials Registration

NCT02654171.     

Short membranous septum length in bicuspid aortic valve stenosis increases the risk of conduction disturbances

BackgroundDistinct anatomical features predispose bicuspid AS patients to conduction disturbances after TAVR. This study sought to evaluate whether the incidence of permanent pacemaker implantation (PPMI) and left bundle branch block (LBBB) in patients with bicuspid aortic stenosis (AS) following transcatheter aortic valve replacement (TAVR) is related to an anatomical association between bicuspid AS and short membranous septal (MS) length.MethodsSixty-seven consecutive patients with bicuspid AS from a Bicuspid AS TAVR multicenter registry and 67 propensity-matched patients with tricuspid ASunderwent computed tomography before TAVR.ResultsMS length was significantly shorter in bicuspid AS compared with tricuspid AS (6.2 ± 2.5 mm vs. 8.4 ± 2.7 mm, respectively; p < 0.001). In patients with bicuspid AS, MS length and aortic valve calcification were the most powerful pre-procedural independent predictors of PPMI or LBBB (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.15 to 1.55, p = 0.003 and OR: 1.92, 95% CI: 1.1 to 3.34, p = 0.022, respectively). When taking into account pre- and post-procedural parameters, aortic valve calcification and the difference between MS length and implantation depth were the most powerful independent predictors of PPMI or LBBB in patients with bicuspid AS (OR: 1.82, 95%: 1.1 to 3.1, p = 0.027; OR: 1.25, 95% CI: 1.10 to 1.38, p = 0.003).ConclusionMS length, which was significantly shorter in bicuspid AS compared with tricuspid AS, aortic valve calcification, and device implantation deeper than MS length predict PPMI or LBBB in bicuspid AS after TAVR.