Exposure to tick-borne encephalitis virus among nature management workers in the Netherlands.

Tick-borne encephalitis virus (TBEV) has only recently been detected in the Netherlands. With still few autochthonous tick-borne encephalitis (TBE) patients, human exposure to TBEV is expected to be very low among the general population. We aimed to assess the exposure to TBEV among persons with an occupationally high risk of tick bites in the Netherlands. In our cross-sectional serological survey, employees and volunteers of nature management organizations provided a single blood sample and completed an online questionnaire in 2017. The sera were screened in the anti-TBEV IgG Enzyme-Linked Immunosorbent Assay (ELISA), after which a TBEV-specific virus neutralization test (VNT) was applied to confirm positive ELISA outcomes. Ten sera tested positive for IgG antibodies in the TBEV ELISA, among 556 participants who did not report vaccination against TBEV. Through confirmation in VNT, TBEV-specific IgG antibodies were detected among 0.5% (3/556, 95%CI 0.1%-1.6%). During the five years prior to the questionnaire, 87% reported tick bites. Half of the participants considered that most of their tick bites (75% to 100%) had been acquired while being at work. A very low seroprevalence of TBEV exposure was observed among these nature management workers, even though they report a six times higher exposure to tick bites, compared to our general population. Nonetheless, the emergence of TBEV in the Netherlands reaffirms the need for education and preventative measures against tick bites and tick-borne diseases.

High risk of positive Trendelenburg test after using the direct lateral approach to the hip compared with the anterolateral approach: a single-centre, randomized trial in patients with femoral neck fracture.

AIMS: The aim of this randomized trial was to compare the functional outcome of two different surgical approaches to the hip in patients with a femoral neck fracture treated with a hemiarthroplasty. PATIENTS AND METHODS: A total of 150 patients who were treated between February 2014 and July 2017 were included. Patients were allocated to undergo hemiarthroplasty using either an anterolateral or a direct lateral approach, and were followed for 12 months. The mean age of the patients was 81 years (69 to 90), and 109 were women (73%). Functional outcome measures, assessed by a physiotherapist blinded to allocation, and patient-reported outcome measures (PROMs) were collected postoperatively at three and 12 months. RESULTS: A total of 11 patients in the direct lateral group had a positive Trendelenburg test at one year compared with one patient in the anterolateral group (11/55 (20%) vs 1/55 (1.8%), relative risk (RR) 11.1; p = 0.004). Patients with a positive Trendelenburg test reported significantly worse Hip Disability Osteoarthritis Outcome Scores (HOOS) compared with patients with a negative Trendelenburg test. Further outcome measures showed few statistically significant differences between the groups. CONCLUSION: The direct lateral approach in patients with a femoral neck fracture appears to be associated with more positive Trendelenburg tests than the anterolateral approach, indicating a poor clinical outcome. Cite this article: Bone Joint J 2019;101-B:793-799.

Biomarkers of muscle damage increased in anterolateral compared to direct lateral approach to the hip in hemiarthroplasty: no correlation with clinical outcome : Short-term analysis of secondary outcomes from a randomized clinical trial in patients with a displaced femoral neck fracture.

In this study, we found elevated levels of serum CK in the anterolateral approach to the hip compared to the direct lateral approach in patients with a displaced femoral neck fracture. No correlation was found between levels of CK and functional outcomes. INTRODUCTION: To compare increase in serum creatine kinase (CK) and its association with functional outcome between the muscle-sparing anterolateral approach and the direct lateral approach to the hip in patients with displaced femoral neck fracture (FNF). METHODS: In this randomized trial, we enrolled eligible patients between 70 and 90 years of age with FNF. Patients were allocated to an uncemented hemiarthroplasty inserted through a direct lateral or an anterolateral approach. The primary endpoints were pain and patient satisfaction assessed by the Visual Analogue Scale (VAS). Among secondary endpoints was increase in CK at 24 and 48 h compared to baseline and its association with surgical parameters, Timed up and Go Test (TUG), Harris Hip Score (HHS), and the presence of a Trendelenburg sign using correlation analysis. This paper reports on increase in serum CK and its association with functional outcome. RESULTS: At 24 h, there was a mean increase from baseline in total CK of 228 U/L (95% CI 187 to 269; P < 0.001). There was a difference between groups at 24 h in CK increase with higher levels in the anterolateral group (mean difference 80 U/L; 95% CI - 0.5 to 162; P = 0.05). Likewise, at 48 h, there was a mean difference of 117 U/L (95% CI 22 to 212; P = 0.01). No correlation was found between CK values and functional assessments. CONCLUSIONS: Compared with the direct lateral approach, the anterolateral approach yielded higher levels of postoperative CK. However, there was no correlation between levels of CK and functional outcome. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02028468.

Blood flow regulation and oxygen uptake during high-intensity forearm exercise.

The vascular strain is very high during heavy handgrip exercise, but the intensity and kinetics to reach peak blood flow, and peak oxygen uptake, are uncertain. We included 9 young (25 ± 2 yr) healthy males to evaluate blood flow and oxygen uptake responses during continuous dynamic handgrip exercise with increasing intensity. Blood flow was measured using Doppler-ultrasound, and venous blood was drawn from a deep forearm vein to determine arteriovenous oxygen difference (a-vO2diff) during 6-min bouts of 60, 80, and 100% of maximal work rate (WRmax), respectively. Blood flow and oxygen uptake increased (P < 0.05) from 60%WRmax [557 ± 177(SD) ml/min; 56.0 ± 21.6 ml/min] to 80%WRmax (679 ± 190 ml/min; 70.6 ± 24.8 ml/min), but no change was seen from 80%WRmax to 100%WRmax Blood velocity (49.5 ± 11.5 to 58.1 ± 11.6 cm/s) and brachial diameter (0.49 ± 0.05 to 0.50 ± 0.06 cm) showed concomitant increases (P < 0.05) with blood flow from 60% to 80%WRmax, whereas no differences were observed in a-vO2diff Shear rate also increased (P < 0.05) from 60% (822 ± 196 s-1) to 80% (951 ± 234 s-1) of WRmax The mean response time (MRT) was slower (P < 0.05) for blood flow (60%WRmax 50 ± 22 s; 80%WRmax 51 ± 20 s; 100%WRmax 51 ± 23 s) than a-vO2diff (60%WRmax 29 ± 9 s; 80%WRmax 29 ± 5 s; 100%WRmax 20 ± 5 s), but not different from oxygen uptake (60%WRmax 44 ± 25 s; 80%WRmax 43 ± 14 s; 100%WRmax 41 ± 32 s). No differences were observed in MRT for blood flow or oxygen uptake with increased exercise intensity. In conclusion, when approaching maximal intensity, oxygen uptake appeared to reach a critical level at ~80% of WRmax and be regulated by blood flow. This implies that high, but not maximal, exercise intensity may be an optimal stimulus for shear stress-induced small muscle mass training adaptations.NEW & NOTEWORTHY This study evaluated blood flow regulation and oxygen uptake during small muscle mass forearm exercise with high to maximal intensity. Despite utilizing only a fraction of cardiac output, blood flow reached a plateau at 80% of maximal work rate and regulated peak oxygen uptake. Furthermore, the results revealed that muscle contractions dictated bulk oxygen delivery and yielded three times higher peak blood flow in the relaxation phase compared with mean values.

Pre-winter lipid stores in brown trout Salmo trutta along altitudinal and latitudinal gradients.

Pre-winter lipid stores of brown trout Salmo trutta L. parr were compared along altitudinal (0-920 m a.s.l.) and latitudinal (58-71° N) gradients. There were increases in lipid content (size adjusted to common lipid-free dry mass of 2·0 g, corresponding to fresh mass of 10 g) with both increasing altitude and latitude. Mean size-adjusted lipid content for S. trutta in high altitude rivers was 60% higher than at low altitude (0·29 and 0·18 g, respectively). Mean size-adjusted lipid content for S. trutta in northern rivers was 30% higher compared to that in southern rivers (0·30 and 0·23 g, respectively). There was a marked between-river variation in mean lipid storage, probably reflecting different strategies or opportunities for the pre-winter acquisition of lipid both locally within rivers and between different populations. This study shows that temperature or winter length, not latitudinal covariates such as annual light regime, governs lipid storage patterns in juvenile salmonids.

Morphological differences in parr of Atlantic salmon Salmo salar from three regions in Norway.

Morphological characters were compared in parr (total length 33-166 mm) of Atlantic salmon Salmo salar sampled from eight wild populations in three regions, three in northern, two in the middle and three in southern Norway, covering a distance of 1700 km (from 70° N to 58° N). On the basis of morphological characters 94·6% of the individuals were correctly classified into the three regions. Discrimination between populations within these three regions also had a high degree of correct classification (89·0-95·8%). Principle component analysis identified largest differences to be in head characters, notably eye diameter and jawbone, with the smallest diameter and head size among the northernmost populations. Fish from the southern rivers had a deeper body form whereas fish from the middle region had larger heads and pectoral fins. This illustrates that S. salar already in the early parr stage has morphological traits, which can be used in discrimination between regions and populations and that these differences are discernible in spite of the volume of escaped farmed fish spawning in Norwegian rivers during the past 30 years.

Aortic Customize: an in vivo feasibility study of a percutaneous technique for the repair of aortic aneurysms using injectable elastomer.

OBJECTIVE: This study aimed to test a percutaneous technique for aneurysm-sac filling by means of in situ polymerisation in an in vivo model. DESIGN: Aortic Customize is a new endovascular treatment concept for aortic aneurysms: a non-cross-linked liquid elastomer is injected to fill the aneurysm sac around a balloon-catheter. With this method, a compliant elastomer mould with a patent lumen is created. MATERIAL: The formulation used in the experiments consisted of a two-component addition-cure liquid-silicone formulation, based on vinyl-terminated polydimethylsiloxane (PDMS). METHODS: The concept of aneurysm-sac filling was tested in vivo in porcine experiments (n = 3). RESULTS: In vivo porcine experiments with the sac-filling application showed successful exclusion of the created aneurysms with patent lumens and absence of endoleaks. The aneurysms were excluded successfully in the in vivo model, injecting elastomer through a 7-French catheter, filling up the entire aneurysm sac. CONCLUSIONS: These in vivo experiments demonstrate that the principle of aneurysm-sac filling by means of in situ curing is feasible, excluding the aneurysm and creating a new lumen. Further long-term animal experiments must be done prior to consideration of clinical application.

[The comparative analysis of high-risk behaviour related to HIV infection in users of psychoactive drugs with stimulating action and opioids].

To study clinical and psychological characteristics associated with high-risk behaviour related to HIV infection in 2006-2007 years, we examined 68 patients with psychoactive drugs (with stimulating action) and opioids (heroin) dependencies. Patients were stratified into 2 groups: users of psychoactive drugs (UPS)--34 patients and opioid users (OU)--34. Behavior of UPS differed from that of OU by using more drug injections per day although the former used syringes of other users less often. Therefore, the risk of being infected was lower in the UPS group compared to the OU group. The evaluation of the risk through sexual transmission did not reveal significant between-group differences.

Pre-winter lipid stores in young-of-year Atlantic salmon along a north-south gradient.

The pre-winter lipid stores of young-of-the-year (YOY, age 0 year) Atlantic salmon Salmo salar were analysed along a north-south gradient from c. 71 to 58 degrees N, with winter conditions ranging from >200 days of ice cover to no ice. The rivers sampled in Northern Norway represent some of the most northerly S. salar rivers. There was an increase in lipid content with increasing latitude, and mean lipid content (size adjusted to common mass) for YOY in northern rivers were almost three times higher: 0.035 g compared to 0.013 g in southern rivers. The relationship was not sensitive to variation in sampling time or variation in YOY body size. The lipid stores, however, varied markedly between rivers and also between neighbouring rivers, indicating different strategies or opportunities for pre-winter lipid storage both at latitudinal and local scales.

The origins of modern proteomes.

Distributions of phylogenetically related protein domains (fold superfamilies), or FSFs, among the three Superkingdoms (trichotomy) are assessed. Very nearly 900 of the 1200 FSFs of the trichotomy are shared by two or three Superkingdoms. Parsimony analysis of FSF distributions suggests that the FSF complement of the last common ancestor to the trichotomy was more like that of modern eukaryotes than that of archaea and bacteria. Studies of length distributions among members of orthologous families of proteins present in all three Superkingdoms reveal that such lengths are significantly longer among eukaryotes than among bacteria and archaea. The data also reveal that proteins lengths of eukaryotes are more broadly distributed than they are within archaeal and bacterial members of the same orthologous families. Accordingly, selective pressure for a minimal size is significantly greater for orthologous protein lengths in archaea and bacteria than in eukaryotes. Alignments of orthologous proteins of archaea, bacteria and eukaryotes are characterized by greater sequence variation at their N-terminal and C-terminal domains, than in their central cores. Length variations tend to be localized in the terminal sequences; the conserved sequences of orthologous families are localized in a central core. These data are consistent with the interpretation that the genomes of the last common ancestor (LUCA) encoded a cohort of FSFs not very different from that of modern eukaryotes. Divergence of bacterial and archaeal genomes from that common ancestor may have been accompanied by more intensive reductive evolution of proteomes than that expressed in eukaryotes. Dollo's Law suggests that the evolution of novel FSFs is a very slow process, while laboratory experiments suggests that novel protein genesis from preexisting FSFs can be relatively rapid. Reassortment of FSFs to create novel proteins may have been mediated by genetic recombination before the advent of more efficient splicing mechanisms.

Frequency- and time-domain femtosecond vibrational sum frequency generation from CO adsorbed on Pt111.

We have studied the effects of intermolecular and intramolecular coupling on the C-O stretching vibration of CO adsorbed on Platinum (111) by means of femtosecond broadband vibrational sum frequency generation (VSFG). Resonant intermolecular coupling is investigated through the coverage dependence of the VSFG signal. The experimental observations can be accurately modeled as lateral coupling of the molecular transition dipole moments; this coupling is invoked in the nonlinear optical response model as a local field correction. The linear polarizability, which appears in this model, is modified by both the dipole-dipole coupling and the population of bridged adsorption sites. By extending the formalism to include these effects, we deduce a vibrational polarizability of 0.32 A(3) from the data. Intramolecular coupling to the frustrated translational mode is observed as temperature dependence of the C-O stretch. The present data can be described either by pertubative or nonpertubative lineshape models from the literature. Measurements of the temperature dependence of the vibrational free induction decay indicate a population relaxation time T(1) of (0.8+/-0.1) ps, in agreement with the observed low-temperature linewidth. Moreover, the ability of this time-domain method to discriminate spectral inhomogeneity yields clear evidence of the order-disorder transition near 275 K. Above this temperature an inhomogeneous linewidth component of (12+/-3) cm(-1) is observed. This value allows us to estimate the structural heterogeneity of the disordered phase, which result agrees with published Monte Carlo simulations.

[Monitoring of vital patient's functions by contact-free sensors]. / Monitoring zhiznennykh funktsii patsienta s ispol'zovaniem sensorov nekontaktnogo tipa.

An experimental device was constructed as well as hardware and software were designed to register the functional state parameters, i.e. external respiration functions, rhythmic heart activity and general motor activity (including the spastic and epileptic variations), when there is no direct galvanic contact with the patient's body.

Application of C1-esterase inhibitor during reperfusion of ischemic myocardium: dose-related beneficial versus detrimental effects.

BACKGROUND: Complement activation during reperfusion of ischemic myocardium augments myocardial injury, and complement inhibition with C1-esterase inhibitor (C1-INH) at the time of reperfusion exerts marked cardioprotective effects in experimental studies. Application of C1-INH in newborns, however, was recently reported to have dangerous and even lethal side effects. This study addresses the essential role of dosage in studies using C1-INH. METHODS AND RESULTS: Cardioprotection by C1-INH was examined in a pig model with 60 minutes of coronary occlusion followed by 120 minutes of reperfusion. C1-INH was administered intravenously 5 to 10 minutes before coronary reperfusion without heparin at a dose of 40, 100, and 200 IU/kg body wt. Compared with the NaCl controls, C1-INH 40 IU/kg reduced myocardial injury (44.1+/-13.8% versus 76.7+/-4.6% necrosis of area at risk, P/=100 IU/kg) of C1-INH will provoke detrimental side effects, probably via its procoagulatory action.

Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori.

Among the several factors that affect the appearance and spread of acquired antibiotic resistance, the mutation frequency and the biological cost of resistance are of special importance. Measurements of the mutation frequency to rifampicin resistance in Helicobacter pylori strains isolated from dyspeptic patients showed that approximately 1/4 of the isolates had higher mutation frequencies than Enterobacteriaceae mismatch-repair defective mutants. This high mutation frequency could explain why resistance is so frequently acquired during antibiotic treatment of H. pylori infections. Inactivation of the mutS gene had no substantial effect on the mutation frequency, suggesting that MutS-dependent mismatch repair is absent in this bacterium. Furthermore, clarithromycin resistance conferred a biological cost, as measured by a decreased competitive ability of the resistant mutants in mice. In clinical isolates this cost could be reduced, indicating that compensation is a clinically relevant phenomenon that could act to stabilize resistant bacteria in a population.

Comparison of repressor and transcriptional attenuator systems for control of amino acid biosynthetic operons.

In bacteria, expression from amino acid biosynthetic operons is transcriptionally controlled by two main mechanisms with principally different modes of action. When the supply of an amino acid is in excess over demand, its concentration will be high and when the supply is deficient the amino acid concentration will be low. In repressor control, such concentration variations in amino acid pools are used to regulate expression from the corresponding amino acid synthetic operon; a high concentration activates and a low concentration inactivates repressor binding to the operator site on DNA so that initiation of transcription is down or up-regulated, respectively. Excess or deficient supply of an amino acid also speeds or slows, respectively, the rate by which the ribosome translates mRNA base triplets encoding this amino acid. In attenuation of transcription, it is the rate by which the ribosome translates such "own" codons in the leader of an amino acid biosynthetic operon that decides whether the RNA polymerase will continue into the operon, or whether transcription will be aborted (attenuated). If the ribosome rate is fast (excess synthesis of amino acid), transcription will be terminated and if the rate is slow (deficient amino acid supply) transcription will continue and produce more messenger RNAs. Repressor and attenuation control systems have been modelled mathematically so that their behaviour in living cells can be predicted and their system properties compared. It is found that both types of control systems are unexpectedly sensitive when they operate in the cytoplasm of bacteria. In the repressor case, this is because amino acid concentrations are hypersensitive to imbalances between supply and demand. In the attenuation case, the reason is that the rate by which ribosomes translate own codons is hypersensitive to the rate by which the controlled amino acid is synthesised. Both repressor and attenuation mechanisms attain close to Boolean properties in vivo: gene expression is either fully on or fully off except in a small interval around the point where supply and demand of an amino acid are perfectly balanced.Our results suggest that repressors have significantly better intracellular performance than attenuator mechanisms. The reason for this is that repressor, but not attenuator, mechanisms can regulate expression from biosynthetic operons also when transfer RNAs are fully charged with amino acids so that the ribosomes work with maximal speed.

Self-reported hyperarousal traits among insomnia patients.

Hyperarousal Scale scores for certain self-reported behaviors reportedly correlate with EEG arousal measures. We tested whether an insomnia subject group had different Hyperarousal Scale scores compared with hypersomnia, delayed sleep phase syndrome, procrastinator or normal subject groups. Compared with 139 normal subjects, mean scores for a group of 256 insomnia subjects was significantly 1.2 S.D. higher on Hyperarousal total scale score, 0.82 S.D. higher on React subscale score and 0.85 S.D. higher on Introspectiveness subscale score. The insomnia group median Extreme score was 2.25 times that of the normal group. These self-report findings suggest that insomnia subjects may be more responsive generally. All sleep disorder groups had increased total Hyperarousal scores, although these increases were accounted for by different scale items. The procrastinator group had Hyperarousal score patterns that generally differed from those of the other groups.

Residual human immunodeficiency virus type 1 infection in lymphoid tissue during highly active antiretroviral therapy: quantitation and virus characterization.

HIV-1 can persist in infected patients despite undetectable plasma viremia. To characterize the residual viral load, repetitive blood and tonsillar samples were collected from 11 HIV-1-positive individuals before and during 96 weeks of therapy with zidovudine, lamivudine, and indinavir. HIV-1 RNA in tonsils was quantified by RT-PCR and infectious HIV-1 provirus by the limiting dilution assay. Genotypic resistance analyses and biological characterization were performed on plasma virus, blood, and tonsillar isolates. Tonsillar infectious HIV-1 provirus and HIV-1 RNA declined by 2 and 3 log(10), respectively, but 10(3)-10(4) cells, less than 0.5% of the total body CD4(+) T cell population carrying infectious HIV-1 provirus, remained involved in active viral replication of drug-sensitive R5 viruses. Thus, the dominant HIV-1 residual infection consists of < or = 10(6) latently infected CD4(+) cells. Plasma HIV-1 RNA decline of > 1.5 log(10) during the first 2 weeks of therapy may indicate low levels of this latent reservoir. Whereas the reservoir of latently infected cells remains stable, actively replicating HIV-1 continuously declines during prolonged antiretroviral therapy. Thus, although viral eradication seems unlikely, antiretroviral therapy may induce an extended period of virologic latency in HIV-1-positive individuals.

Fluctuations in repressor control: thermodynamic constraints on stochastic focusing.

The influence of fluctuations in molecule numbers on genetic control circuits has received considerable attention. The consensus has been that such fluctuations will make regulation less precise. In contrast, it has more recently been shown that signal fluctuations can sharpen the response in a regulated process by the principle of stochastic focusing (SF) (, Proc. Natl. Acad. Sci. USA. 97:7148-7153). In many cases, the larger the fluctuations are, the sharper is the response. Here we investigate how fluctuations in repressor or corepressor numbers can improve the control of gene expression. Because SF is found to be constrained by detailed balance, this requires that the control loops contain driven processes out of equilibrium. Some simple and realistic out-of-equilibrium steps that will break detailed balance and make room for SF in such systems are discussed. We conclude that when the active repressors are controlled by corepressor molecules that display large ("coherent") number fluctuations or when corepressors can be irreversibly removed directly from promoter-bound repressors, the response in gene activity can become significantly sharper than without intrinsic noise. A simple experimental design to establish the possibility of SF for repressor control is suggested.