Exercise intensity alters postexercise hypotension

OBJECTIVE: Blood pressure (BP) is immediately lowered after a session of dynamic exercise, e.g. postexercise hypotension (PEH). The optimal exercise intensity needed to evoke PEH has not been established. We examined the effect of light (LITE) and moderate (MOD) exercise intensity on PEH. DESIGN: Subjects were 49 men (mean +/- SEM, 43.8 +/- 1.4 years) with high normal to stage 1 hypertension (145.0 +/- 1.5/85.8 +/- 1.1 mmHg). Men randomly completed three blinded experiments: a control session and two cycle exercise bouts, one at 40% (LITE) and the other at 60% (MOD) of maximal oxygen consumption. METHODS: Experiments began with a baseline period and were conducted at the same time of day and separated by >/= 2 days. Subjects wore an ambulatory BP monitor after the experiments. Repeated measure analysis of variance (ANOVA) tested if BP and heart rate differed over time and between experimental conditions. Multivariate regression tested factors related to the BP response. RESULTS: For 9 h after all experiments, average awake systolic blood pressure (SBP) increased and diastolic blood pressure (DBP) decreased compared with baseline (P < 0.001). Average awake SBP increased up to 6.9 mmHg less (P < 0.001) and DBP decreased 2.6 mmHg more (P < 0.05) after exercise versus control. For 5 h, PEH was greater after MOD; but over the course of 9 h, LITE was as effective as MOD in eliciting PEH. Baseline BP was the primary factor explaining the BP response (beta = -0.434 to -0.718, r = 0.096-0.295). CONCLUSIONS: LITE and MOD evoked PEH throughout the daytime hours. Lower intensity dynamic exercise such as walking, contributes to BP control in men with hypertension.     

Preventing the risk of coronary injury in posteroseptal accessory pathway ablation in children: different strategies and advantages of fluoroscopy integrated 3D-mapping system (CARTO-UNIVU™)

Purpose

To evaluate various strategies in order to minimize the risk of coronary injury during posteroseptal accessory pathways ablation in children.

Methods

We retrospectively reviewed 68 posteroseptal accessory pathways ablation procedures (20 decremental and 48 typical accessory pathways) performed in 62 pediatric patients at our institution between July 2009 and December 2016. Only posteroseptal accessory pathways targeted near or within the coronary sinus were included and ablation was mostly performed using irrigated tip radiofrequency.

Results

Median patient age was 11 years with a median body weight of 39 kg. Thirty patients underwent a coronary angiogram, 21 were coupled to the 3D navigation system CARTO-UNIVU?. The coronary angiogram showed a distance of less than 5 mm between the coronary artery and the ablation site in 40% of our cases; 3 patients had a coronary injury related to RF ablation, 6 patients were switched for cryoablation, 3 patients received limited RF energy (20 W). There were no demographic data predicting the proximity of the coronary artery to the ablation site.

Conclusion

Ablation of posteroseptal accessory pathways specifically in children carries a risk of coronary artery injury which is probably underestimated. The use of merged 3D images and coronary angiograms, the reduction of RF energy or the switch to cryoablation are possible alternatives to limit the risk of coronary injury.

     

Assessment of Parkinson's disease risk loci in Greece

Genome-wide association studies (GWAS) have been shown to be a powerful approach to identify risk loci for neurodegenerative diseases. Recent GWAS in Parkinson's disease (PD) have been successful in identifying numerous risk variants pointing to novel pathways potentially implicated in the pathogenesis of PD. Contributing to these GWAS efforts, we performed genotyping of previously identified risk alleles in PD patients and control subjects from Greece. We showed that previously published risk profiles for Northern European and American populations are also applicable to the Greek population. In addition, although our study was largely underpowered to detect individual associations, we replicated 5 of 32 previously published risk variants with nominal p values <0.05. Genome-wide complex trait analysis revealed that known risk loci explain disease risk in 1.27% of Greek PD patients. Collectively, these results indicate that there is likely a substantial genetic component to PD in Greece, similarly to other worldwide populations, that remains to be discovered.     

Microfluidic device performing on flow study of serial cell–cell interactions of two cell populations

In this study we present a novel microfluidic hydrodynamic trapping device to probe the cell–cell interaction between all cell samples of two distinct populations. We have exploited an hydrodynamic trapping method using microfluidics to immobilize a batch of cells from the first population at specific locations, then relied on hydrodynamic filtering principles, the flowing cells from the second cell population are placed in contact with the trapped ones, through a roll-over mechanism. The rolling cells interact with the serially trapped cells one after the other. The proposed microfluidic phenomenon was characterized with beads. We have shown the validity of our method by detecting the capacity of olfactory receptors to induce adhesion of cell doublets overexpressing these receptors. We report here the first controlled on-flow single cell resolution cell–cell interaction assay in a microfluidic device for future application in cell–cell interactions-based cell library screenings.

In this study we present a novel microfluidic hydrodynamic trapping device to probe the cell–cell interaction between all cell samples of two distinct populations.     

Structure-relaxation mechanism for the response of T4 lysozyme cavity mutants to hydrostatic pressure

Application of hydrostatic pressure shifts protein conformational equilibria in a direction to reduce the volume of the system. A current view is that the volume reduction is dominated by elimination of voids or cavities in the protein interior via cavity hydration, although an alternative mechanism wherein cavities are filled with protein side chains resulting from a structure relaxation has been suggested [López CJ, Yang Z, Altenbach C, Hubbell WL (2013) Proc Natl Acad Sci USA 110(46):E4306–E4315]. In the present study, mechanisms for elimination of cavities under high pressure are investigated in the L99A cavity mutant of T4 lysozyme and derivatives thereof using site-directed spin labeling, pressure-resolved double electron–electron resonance, and high-pressure circular dichroism spectroscopy. In the L99A mutant, the ground state is in equilibrium with an excited state of only ∼3% of the population in which the cavity is filled by a protein side chain [Bouvignies et al. (2011) Nature 477(7362):111–114]. The results of the present study show that in L99A the native ground state is the dominant conformation to pressures of 3 kbar, with cavity hydration apparently taking place in the range of 2–3 kbar. However, in the presence of additional mutations that lower the free energy of the excited state, pressure strongly populates the excited state, thereby eliminating the cavity with a native side chain rather than solvent. Thus, both cavity hydration and structure relaxation are mechanisms for cavity elimination under pressure, and which is dominant is determined by details of the energy landscape.Proteins in solution exist in conformational equilibria that cannot be appreciated from structures observed in crystal lattices (1–5). The members of a folded conformational ensemble may have distinct functions and hence are of interest in elucidating mechanisms of protein action (5–7). The free-energy differences between the conformations can range from zero to a few kilocalories per mole; the higher free-energy states are referred to as “invisible” or “excited” (E) states owing to their low equilibrium populations. The structural transition between the native ground state (G) and the E state may involve rigid body motion of the peptide backbone (5, 8) or local unfolding (9).For a complete understanding of molecular mechanisms underlying function, characterization of functionally relevant conformational substates is required. However, in the case of E states, low populations and short lifetimes present a challenge for biophysical characterization. The elegant high-resolution NMR studies from Akasaka (10, 11) and coworkers suggest that application of hydrostatic pressure on the order of a few kilobars may solve this problem by reversibly populating functional E states, making them amenable for study by spectroscopic methods. For example, high-pressure NMR has been used to identify and characterize E states crucial to ligand binding in ubiquitin (12) and dihydrofolate reductase (13). As a result, high-pressure biophysics is currently of mainstream interest in protein science.Application of sufficiently high pressure leads to population of a “pressure-denatured” state. For many proteins this state retains a relatively compact fold, at least near neutral pH and in the absence of denaturants, and is thus distinct from the unfolded states produced thermally or by chemical denaturants wherein both secondary and tertiary structures are largely lost (14–20). The pressure-denatured state is often labeled as the “unfolded state” (10), but here we reserve the term “unfolded” to describe a state with little tertiary or secondary structure. In this paper attention is focused on moderate pressures (<4 kbar) that shift conformational equilibria rather than leading to a pressure-denatured state.Pressure shifts equilibria in a direction to reduce the total volume of the system. The current view is that the volume reduction that accompanies pressure-modulated transitions in proteins, including formation of the denatured state, is dominated by the elimination of voids or cavities in the protein’s interior (14, 21–24) via hydration, although other factors contribute (15, 25–28). In the equilibrium between two folded conformations, G ↔ E for example, an alternative “structure-relaxation” mechanism may play a role in the pressure response. In this model, voids are eliminated by pressure owing to an increase in the population of an alternative packing arrangement of the core in which cavities are filled with native side chains rather than solvent. This model has been suggested to play a role in certain proteins at high pressure (1, 29–31), although to our knowledge direct observation of structure relaxation under pressure has not been reported.That a structure-relaxation mechanism may play a role in the pressure response is suggested by recent studies of cavity-creating mutants in T4 lysozyme (T4L) at atmospheric pressure (1). Although the crystal structures of the cavity mutants are nearly identical to those of the WT protein (32–35), in solution there are multiple conformations in equilibrium (1, 4). For example, in the T4L cavity mutants L121A/L133A, L133G, and W138A, two conformations of similar free energy were identified in solution (1). Perhaps the most extensively investigated cavity-forming mutation is T4L L99A that enlarges a preexisting cavity in the rigid four-helix bundle of the protein. In this mutant, a minor conformation (E) in equilibrium with the ground state (G) was detected that accounted for ∼3% of the population (4, 36). Remarkably, in each of the above cavity-creating mutants, one member of the conformational ensemble corresponds to a structural rearrangement that fills the cavity with a side chain; for L99A it is Phe114 that occupies the engineered cavity (5). Such conformations in which cavities are absent or reduced are expected to have a lower molar volume, and thus may be populated by pressure.The pressure dependence of the L99A mutant was recently studied with NMR methods by Nucci et al. (27) and independently by Maeno et al. (31). In the study of Maeno et al. (31), the disappearance of cross-peaks in a ¹H-¹³C heteronuclear single-quantum coherence (HSQC) NMR experiment at pressures up to 3 kbar was interpreted to reflect an increase in population of the E conformation with Phe114 occupying the cavity, consistent with a structure-relaxation mechanism rather than cavity hydration or unfolding. However, based on ¹H-¹⁵N HSQC NMR studies on the same protein, Nucci et al. (27) concluded that cavity hydration and unfolding occurred at pressures less than 2.5 kbar rather than populating the E conformation. Commentaries on these conflicting interpretations were recently published (37, 38).In the present study, we investigate the pressure dependence of T4L WT*, L99A, and L99A containing the additional mutations G113A and G113A/R119P, both of which have been shown to lower the free energy of the E conformation and hence increase the equilibrium population (5). The experimental approach is based on site-directed spin labeling EPR (SDSL-EPR) and the recently developed technologies of high-pressure continuous wave (CW) EPR spectroscopy for SDSL (30, 39), pressure-resolved double electron–electron resonance (PR DEER) spectroscopy (40), and high-pressure circular dichroism (HP-CD) (30). HP-CD reveals the global secondary structure of the protein at pressures up to 2.4 kbar. CW EPR line shapes of spin-labeled proteins are sensitive to backbone fluctuations on the nanosecond time scale (41, 42) and can unambiguously identify site-specific unfolding under pressure to 4 kbar, as well as identify sequences in slow conformational exchange on the microsecond–millisecond time scale (30, 39). The intrinsic time scale of SDSL-EPR is much shorter than NMR, such that spectral averaging of microsecond–millisecond protein conformational exchange does not occur. Hence, EPR spectra of a spin-labeled protein provide a “snapshot” of conformational equilibria frozen in time. Although the CW spectra can reveal conformational equilibria with exquisite sensitivity, they do not provide quantitative information on the structures involved or resolve the true heterogeneity of a conformational manifold. This information is uniquely provided by distance mapping using pairs of spin labels and DEER spectroscopy. At the present state of development, PR DEER allows direct structure mapping of the states populated by pressure to 6 kbar.The results reported below indicate that at pressures up to 2.4 kbar the secondary structure content of T4L L99A is unchanged, eliminating the possibility of global or subglobal unfolding of the helical C domain, in agreement with the results of Maeno et al. (31). Collectively, the data do not support a large-scale shift to the E conformation of T4L L99A under high pressure, but rather cavity hydration and finally transition to a partially disordered state at pressures of 4 kbar. However, pressure strongly shifts the G ↔ E equilibrium toward E in the presence of the additional G113A and R119P mutations that lower the energy of the E conformation, thus demonstrating a structure-relaxation mechanism for the pressure response. Moreover, ligand binding to the engineered cavity strongly stabilizes the G conformation. Taken together, the results show that both cavity hydration and structure relaxation are valid models for the pressure dependence in proteins, and which prevails depends on the details of the energy landscape.     

Navigating Language Barriers: A Systematic Review of Patient Navigators’ Impact on Cancer Screening for Limited English Proficient Patients

OBJECTIVES

To systematically review the literature on the impact of patient navigators on cancer screening for limited English proficient (LEP) patients.

DATA SOURCES

Electronic databases (PubMed, PsycINFO via OVID, Web of Science, Cochrane, EMBASE, and Scopus) through 8 May 2015.

ELIGIBILITY CRITERIA

Articles in this review had: (1) a study population of LEP patients eligible for breast, cervical or colorectal cancer screenings, (2) a patient navigator intervention to provide services prior to or during cancer screening, (3) a comparison of the patient navigator intervention to either a control group or another intervention, and (4) language-specific outcomes related to the patient navigator intervention.

STUDY APPRAISAL

We assessed the quality of the articles using the Downs and Black Scale.

RESULTS

Fifteen studies met the inclusion criteria and evaluated the screening rates for breast, colorectal, and cervical cancer in 15 language populations. Fourteen studies resulted in improved screening rates for LEP patients between 7 and 60 %. There was great variability in the patient navigation interventions evaluated. Training received by navigators was not reported in nine of the studies and no studies assessed the language skills of the patient navigators in English or the target language.

LIMITATIONS

This study is limited by the variability in study designs and limited reporting on patient navigator interventions, which reduces the ability to draw conclusions on the full effect of patient navigators.

CONCLUSIONS

Overall, we found evidence that navigators improved screening rates for breast, cervical and colorectal cancer screening for LEP patients. Future studies should systematically collect data on the training curricula for navigators and assess their English and non-English language skills in order to identify ways to reduce disparities for LEP patients.

     

Incidence,management and outcome of respiratory syncytial virus infection in adult lung transplant recipients: a 9-year retrospective multicentre study

ObjectivesTo analyse functional outcome parameters according to antimicrobial treatments after respiratory syncytial virus (RSV)-confirmed infection in adult lung transplant recipients.MethodsA 9-year retrospective multicentre cohort study (2011–19) included adult lung transplant recipients with RSV-confirmed infection. The first endpoint determined new allograft dysfunction (acute graft rejection and chronic lung allograft dysfunction (CLAD)) 3 months after infection. Then baseline and 3 months' postinfection forced expiratory volume in 1 second (FEV₁) values were compared according to antimicrobial treatment. Univariate logistic regression analysis was performed.ResultsRSV infection was confirmed in 77 of 424 lung transplant recipients (estimated incidence of 0.025 per patient per year; 95% confidence interval 0.018–0.036). At 3 months, 22 recipients (28.8%) developed allograft dysfunction: ten (13%) possible CLAD, six (7.9%) acute rejection and six (7.9%) CLAD. Recipients with the lowest preinfection FEV₁ had a greater risk of developing pneumonia (median (interquartile range) 1.5 (1.1–1.9) vs. 2.2 (1.5–2.4) L/s, p 0.003) and a higher odds of receiving antibiotics (1.6 (1.3–2.3) vs. 2.3 (1.9–2.5) L/s, p 0.017; odds ratio 0.52, 95% confidence interval 0.27–0.99). Compared to tracheobronchitis/bronchiolitis, RSV-induced pneumonia led more frequently to hospitalization (91.7%, 22 vs. 58.0%, 29, p 0.003) and intensive care unit admission (33.3%, 8 vs. 0, p < 10^-3). For ribavirin-treated recipients (24.7%, 19) and azithromycin prophylaxis (50.6%, 39), 3-month FEV₁ values were not different from untreated recipients. The overall mortality was 2.5% at 1 month and 5.3% at 6 months, unrelated to RSV.ConclusionsAt 3 months after RSV-confirmed infection, 22 recipients (28.8%) had new allograft dysfunction. Ribavirin treatment and azithromycin prophylaxis did not prevent FEV₁ decline.     

Microbial methanogenesis in subsurface oil and coal

It is now clear that active methanogens are present in the deep-subsurface. This paper reviews microbial population structures and the biodegradation of organic compounds to methane in situ within oil reservoirs and coal deposits. It summarizes our current knowledge of methanogenes and methanogenesis, fermenters, synthrophs and microbial metabolism of complex organic compounds in these two widely occurring organic-rich subsurface environments. This review is not intended to be an exhaustive report of microbial diversity. Rather, it illustrates the similarities and differences between the two environments with specific examples, from the nature of the organic molecules to the methanogenic metabolic pathways and the structure of the microbial populations to demonstrate that widely diverging microbial populations show surprisingly similar metabolic capabilities.     

Predictive factors of women’s subjective perception of childbirth experience: a systematic review of the literature

ABSTRACT

Background: Up to 33% of women report a negative or traumatic childbirth experience. Given this high prevalence and its consistent association with adverse postpartum and child outcomes, it is essential to identify predictive factors and to improve the management of the childbirth experience.

Objective: This systematic review explores and identifies risk and protective factors for women’s subjective childbirth experience and birth satisfaction by reviewing original research.

Methods: A systematic search was performed for childbirth experience literature on three online databases. Reviewed papers focused on women’s subjective childbirth experience and its predictive factors. The articles were assessed with the Mixed Methods Appraisal Tool (MMAT).

Results: Risk and protective factors are notably different depending on the study design, the country, or the method employed. The main risk factors are obstetric, such as emergency caesarean and highly perceived labour pain, and women’s dissatisfaction with social support. The main protective factors are: obstetric, including highly perceived control during labour or satisfaction regarding partner’s support. However, overall results are inconclusive for methodological or conceptual reasons.

Conclusions: Several risk factors can be identified through pregnancy or childbirth. This underlines the importance of the quality of maternal interpersonal and professional relationships, especially with first-line perinatal health-care professionals, such as midwives.