Miracle-dz/UniFAR-FTUs huggingface dataset:
Detraining and Bone Effect of Exercise on Bone Mass and Structure with Special Reference to Maintenance of the Exercise-induced Bone

Kontulainen, Saija Training, detraining and bone Effect of exercise on bone mass and structure with special reference to maintenance of exercise induced bone gain Jyväskylä: University of Jyväskylä, 2002, 70 p. (Studies in Sport, Physical Education and Health, ISSN 0356-1070; 88) ISBN 951-39-1294-9 Finnish summary Diss. The objectives of this thesis were to investigate the effects of long-term mechanical loading on mass, size and mechanical strength of bone in male and female racquet sports players and to evaluate the maintenance of exercise-induced bone gain in these players during the following years of reduced training. In addition, bone maintenance was assessed after jumping exercise interventions in pubertal girls and premenopausal women. Altogether 223 subjects were involved in the study serie. The cross-sectional comparisons of bone mass, structure and strength between playing and nonplaying arm of racquet sports players showed that playing had increased bone size but not volumetric density of cortical bone. The loaded bone shaft seemed to have grown periosteally leading to 11-34% greater estimated bone strength in the loaded arm compared to its counterpart. In female players, this exercise-induced benefit in bone strength was more than two times greater if starting age of the activity had been before the onset of puberty. Prospective 4and 5-year follow-up studies of male and female racquet sports players and their controls revealed that despite reduced training the exerciseinduced bone gain was well maintained in all groups of players regardless of the starting age of activity (either in growing years or in adulthood) and different amount of exercise-induced bone gain. Changes in training were weakly related to the changes in the side-to-side BMC difference even among players who had completely stopped training a minimum one year before the follow-up. As regards, the maintenance of the effects of jumping interventions on bone and physical performance were evaluted in perimenarcheal girls and in premenopausal females. Girls’ follow-up showed that although the greatest proportion of bone mineral accrual was attributable to growth, an additional bone gain achieved by jumping training was maintained at the lumbar spine at least a year after the end of the training. In premenopausal women, the significant bone gain that was obtained by 18-month high-impact exercise was well maintained three and half years after the end of the intervention, while the exercise-induced improvements in the neuromuscular performance had returned to the baseline level. All these findings emphasise long-term benefits of exercise on bone. Therefore, exercise can be recommended for preventing osteoporosis and related fractures.
Efficacy and Safety of Crofelemer for Noninfectious Diarrhea in HIV-Seropositive Individuals (ADVENT Trial): A Randomized, Double-Blind, Placebo-Controlled, Two-Stage Study

Abstract Background: HIV-associated diarrhea remains a significant concern with limited treatment options. Objective: To determine the optimal dose, efficacy, and safety of crofelemer for noninfectious diarrhea. Methods: This randomized, double-blind, phase 3 trial used a 2-stage design. Both stages included 2-week screening, 4-week placebo-controlled treatment, and 20-week placebo-free (open-label) extension phases. In stage I, 196 HIV-seropositive patients with chronic diarrhea were randomized to crofelemer 125 mg, 250 mg, or 500 mg or placebo twice daily. Using a prospective analysis, the 125-mg twice-daily dose was selected for stage II. In stage II, 180 new patients were randomized to crofelemer 125 mg twice daily or placebo for 4 weeks. Primary efficacy analysis was the percentage of patients (stages I/II combined) who achieved clinical response (defined as ≤2 watery stools/week during ≥2 of 4 weeks). During the placebo-free extension phase, response (≤2 watery stools) was assessed weekly. Results: Significantly more patients receiving crofelemer 125 mg achieved clinical response versus placebo (17.6% vs 8.0%; one-sided, P = .01). Crofelemer 125 mg resulted in a greater change from baseline in number of daily watery bowel movements (P = .04) and daily stool consistency score (P = .02) versus placebo. During the placebo-free extension phase, percentages of weekly responders ranged from 40% to 56% at weeks 11 to 24. Crofelemer was minimally absorbed, well tolerated, did not negatively impact clinical immune parameters, and had a safety profile comparable to placebo. Conclusions: In HIV-seropositive patients taking stable antiretroviral therapy, crofelemer provided significant improvement in diarrhea with a favorable safety profile.
Teasing Apart the Many Effects of Lighting Environment on Opsin Expression and Foraging Preference in Bluefin Killifish

Coloration and color vision covary with lighting in many taxa. Determining the mechanisms underlying these patterns is difficult because lighting environments can have multiple effects on signaling that occur at multiple timescales. Lighting environments can (1) immediately affect signal propagation and transmission, which determine the radiance spectrum reaching the receiver; (2) induce variation in visual systems via developmental plasticity; and (3) lead to genetic differences in visual systems due to a history of selection in different habitats. We tease apart these effects on pecking preference and examine the relationship between pecking preference and opsin expression. Using killifish from two visually distinct populations (clear vs. tea‐stained water), we performed crosses (genetics), raised animals under different lighting conditions (developmental plasticity), and assayed the preference to peck at different‐colored dots under different lighting conditions (immediate effects). Pecks are interpreted as foraging preference. Developmental plasticity affected both pecking preference and opsin expression. Lighting environments also had immediate effects on pecking preference, but these depended on the lighting conditions animals experienced during development. Genetic effects were detected in opsin expression, but there were no corresponding effects on pecking preference. Overall, only 3.36% of the variation in pecking preference was accounted for by opsin expression.
The Molecular Basis of High-Altitude Adaptation in Deer Mice

Elucidating genetic mechanisms of adaptation is a goal of central importance in evolutionary biology, yet few empirical studies have succeeded in documenting causal links between molecular variation and organismal fitness in natural populations. Here we report a population genetic analysis of a two-locus α-globin polymorphism that underlies physiological adaptation to high-altitude hypoxia in natural populations of deer mice, Peromyscus maniculatus. This system provides a rare opportunity to examine the molecular underpinnings of fitness-related variation in protein function that can be related to a well-defined selection pressure. We surveyed DNA sequence variation in the duplicated α-globin genes of P. maniculatus from high- and low-altitude localities (i) to identify the specific mutations that may be responsible for the divergent fine-tuning of hemoglobin function and (ii) to test whether the genes exhibit the expected signature of diversifying selection between populations that inhabit different elevational zones. Results demonstrate that functionally distinct protein alleles are maintained as a long-term balanced polymorphism and that adaptive modifications of hemoglobin function are produced by the independent or joint effects of five amino acid mutations that modulate oxygen-binding affinity.
Binding Stoichiometry and Kinetics of the Interaction of a Human Anthrax Toxin Receptor, CMG2, with Protective Antigen*

The protective antigen (PA) moiety of anthrax toxin binds to cellular receptors and mediates entry of the two enzymatic moieties of the toxin into the cytosol. Two PA receptors, anthrax toxin receptor (ATR)/tumor endothelial marker 8 (TEM8) and capillary morphogenesis protein 2 (CMG2), have been identified. We expressed and purified the von Willebrand A (VWA) domain of CMG2 and examined its interactions with monomeric and heptameric forms of PA. Monomeric PA bound a stoichiometric equivalent of CMG2, whereas the heptameric prepore form bound 7 eq. The Kd of the VWA domain-PA interaction is 170 pm when liganded by Mg2+, reflecting a 1000-fold tighter interaction than most VWA domains with their endogenous ligands. The dissociation rate constant is extremely slow, indicating a 30-h lifetime for the CMG2·PA monomer complex. CMG2 metal ion-dependent adhesion site (MIDAS) was studied kinetically and thermodynamically. The association rate constant (∼105 m-1 s-1) is virtually identical in the presence or absence of Mg2+ or Ca2+, but the dissociation rate of metal ion liganded complex is up to 4 orders of magnitude slower than metal ion free complex. Residual affinity (Kd ∼ 960 nm) in the absence of divalent metal ions allowed the free energy for the contribution of the metal ion to be calculated as 5 kcal mol-1, demonstrating that the metal ion-dependent adhesion site is directly coordinated by CMG2 and PA in the binding interface. The high affinity of the VWA domain for PA supports its potency in neutralizing anthrax toxin, demonstrating its potential utility as a novel therapeutic for anthrax.
Role of Iron Uptake Systems in Pseudomonas aeruginosa Virulence and Airway Infection

ABSTRACT Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and chronic lung infections in cystic fibrosis patients. Iron is essential for bacterial growth, and P. aeruginosa expresses multiple iron uptake systems, whose role in lung infection deserves further investigation. P. aeruginosa Fe3+ uptake systems include the pyoverdine and pyochelin siderophores and two systems for heme uptake, all of which are dependent on the TonB energy transducer. P. aeruginosa also has the FeoB transporter for Fe2+ acquisition. To assess the roles of individual iron uptake systems in P. aeruginosa lung infection, single and double deletion mutants were generated in P. aeruginosa PAO1 and characterized in vitro, using iron-poor media and human serum, and in vivo, using a mouse model of lung infection. The iron uptake-null mutant (tonB1 feoB) and the Fe3+ transport mutant (tonB1) did not grow aerobically under low-iron conditions and were avirulent in the mouse model. Conversely, the wild type and the feoB, hasR phuR (heme uptake), and pchD (pyochelin) mutants grew in vitro and caused 60 to 90% mortality in mice. The pyoverdine mutant (pvdA) and the siderophore-null mutant (pvdA pchD) grew aerobically in iron-poor media but not in human serum, and they caused low mortality in mice (10 to 20%). To differentiate the roles of pyoverdine in iron uptake and virulence regulation, a pvdA fpvR double mutant defective in pyoverdine production but expressing wild-type levels of pyoverdine-regulated virulence factors was generated. Deletion of fpvR in the pvdA background partially restored the lethal phenotype, indicating that pyoverdine contributes to the pathogenesis of P. aeruginosa lung infection by combining iron transport and virulence-inducing capabilities.
SYNTHESIS, TOXICITY AND APPLICATIONS OF DOPED CARBON NANOTUBES

By doping carbon nanotubes it is possible to alter significantly the electronic, mechanical and chemical properties of the tubes. This possibility opens up new avenues in the production of nanomaterials with desired properties using different dopants. Therefore, the controlled production of N-doped carbon nanotubes will be discussed. The field emission properties of doped tubes, their use as gas sensors or protein immobilizers will also be discussed. It will be also demonstrated that Ag and Au particles could be easily anchored on the surface of N-doped nanotubes. Possible mechanisms will be discussed. We will present the first results related to the fabrication of CNx nanotube–polystyrene (PS) composites, which were produced by a novel polymerization technique using a “grafting from” route using Nitroxide Mediated Radical Polymerization (NMRP) and atomic transfer radical polymerization (ATRP). We demonstrate using HRTEM and EELS that the tube material was covalently bonded to the PS chains, thus forming brush-like structures. These polymerized CNx nanotubes form uniform dispersions in organic solvents. The results are novel and constitute will results in further developments related to the chemistry of CNx nanotubes and fabrication of novel polymer composites.Finally, the bio-applications of CNx nanotubes will be discussed in detail. In particular, comparative toxicological studies of CNx MWNTs and pure carbon multi-walled nanotubes (MWNTs) on mice reveal that CNx tubes appear to be far less harmful. For example, using extreme high doses of CNx nanotubes (e.g. 5mg/kg), no lethal effects were observed on the mice, which is in contrast to previous reports using MWNTs or SWNTs. Interestingly, pure MWNTs appeared to be lethal at all doses tested for intratracheal instilation, whereas CNx MWNTs were not. We also carried out a detailed cell viability study with amoeba and different types of nanotubes: pure carbon MWNTs and N-doped MWNTs. We found that when the cells were incubated with CNx MWNTs, they survived and even proliferated at all doses tested. In contrast, most of the amebas’ population died after 8 hs of incubation with undoped MWCNTs. Therefore, we believe that CNx nanotubes are more biocompatible when compared to undoped nanotubes (either singleor multi-walled).
Impact and Effectiveness of 10 and 13-Valent Pneumococcal Conjugate Vaccines on Hospitalization and Mortality in Children Aged Less than 5 Years in Latin American Countries: A Systematic Review

Background Several Latin American and Caribbean (LAC) countries have introduced pneumococcal conjugate vaccine (PCV-10 or PCV-13) in their routine national immunization programs. Objectives We aimed to summarize the evidence of PCV impact and effectiveness in children under 5 years old in the LAC Region. Methods We conducted a systematic review of the literature on impact or effectiveness of PCVs on deaths or hospitalizations due to invasive pneumococcal disease (IPD), pneumonia, meningitis and sepsis. We searched Medline, WoS, Lilacs, Scopus, Central and gray literature published in any language from 2009 to January 2016. We included studies addressing the outcomes of interest in children in the target age group, and with the following designs: randomized trials, cohort or case-control, interrupted time series with at least three data points before and after the intervention, and before-after studies. Screening of citations, data extraction, and risk of bias assessment were conducted in duplicate by independent reviewers, according to the study protocol registered on PROSPERO. Descriptive analysis of the effectiveness measurements and sensitivity analysis were conducted. Effectiveness is reported as 1-OR or 1-RR for case control or cohort/clinical trials, and as percent change of disease incidence rates for before-after studies. Results We identified 1,085 citations, 892 from databases and 193 from other sources. Of these, 22 were further analyzed. Studies were from Brazil, Chile, Uruguay, Argentina, Peru and Nicaragua. Effectiveness ranged from 8.8–37.8% for hospitalizations due to X-ray confirmed pneumonia, 7.4–20.6% for clinical pneumonia, and 13.3–87.7% for meningitis hospitalizations, and 56–83.3% for IPD hospitalization, varying by age, outcome definition, type of vaccine and study design. Conclusions Available evidence to date indicates significant impact of both PCV-10 and PCV-13 in the outcomes studied, with no evidence of the superiority of one vaccine over the other on pneumonia, IPD or meningitis hospitalization reduction in children under 5 years old.
Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.

BACKGROUND Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma. METHODS In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival. RESULTS At a median follow-up of 13.5 months in a protocol-specified interim analysis, 169 events of disease progression or death were observed (in 53 of 286 patients [18.5%] in the daratumumab group vs. 116 of 283 [41.0%] in the control group; hazard ratio, 0.37; 95% confidence interval [CI], 0.27 to 0.52; P<0.001 by stratified log-rank test). The Kaplan-Meier rate of progression-free survival at 12 months was 83.2% (95% CI, 78.3 to 87.2) in the daratumumab group, as compared with 60.1% (95% CI, 54.0 to 65.7) in the control group. A significantly higher rate of overall response was observed in the daratumumab group than in the control group (92.9% vs. 76.4%, P<0.001), as was a higher rate of complete response or better (43.1% vs. 19.2%, P<0.001). In the daratumumab group, 22.4% of the patients had results below the threshold for minimal residual disease (1 tumor cell per 105 white cells), as compared with 4.6% of those in the control group (P<0.001); results below the threshold for minimal residual disease were associated with improved outcomes. The most common adverse events of grade 3 or 4 during treatment were neutropenia (in 51.9% of the patients in the daratumumab group vs. 37.0% of those in the control group), thrombocytopenia (in 12.7% vs. 13.5%), and anemia (in 12.4% vs. 19.6%). Daratumumab-associated infusion-related reactions occurred in 47.7% of the patients and were mostly of grade 1 or 2. CONCLUSIONS The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened progression-free survival among patients with relapsed or refractory multiple myeloma. Daratumumab was associated with infusion-related reactions and a higher rate of neutropenia than the control therapy. (Funded by Janssen Research and Development; POLLUX ClinicalTrials.gov number, NCT02076009 .).
Critical role of Jun N-terminal Kinase and p 38 in the pathogenesis of sepsis-induced down regulation of the renal outer medullary K + channel-1 expression

Objective: In sepsis, renal expression of the renal outer medullary K+ channel-1 (ROMK) is impaired via NFkB-induced cytokines. Mitogen activated protein kinases (MAPKs) are induced by lipopolysaccharide (LPS) or proinflammatory cytokines and ROMK-1 expression is downregulated via p38 or Jun N-terminal kinase (JNK). We investigated how MAPK-inhibition of p38 or JNK affects ROMK-1 during sepsis. Material and methods: Male C57/BL-6 mice (20–25 g) were used for in vivo and murine CCD cells (M1 cell line) for in vitro investigations. Mice were treated with LPS and MAPKs were inhibited by siRNA. M1 cells were stimulated with LPS or cytokines in addition to pathway inhibitors. In vivo, IL1b, TNFa and INFg in blood were detected by cytometric bead immunoassay. In vitro, M1-cell line and a ROMK reporter gen assay were used. Results: In vivo, LPS increased cytokines and decreased renal ROMK-1. Inhibition of JNK diminished LPS induction of cytokines and decrease of ROMK-1. JNK/p38 in kidney tissue were not changed after LPS nor affected by either MAPK inhibition, indicating that the regulation observed is due to cytokine-release in circulating macrophages. Incubation of M1-cells with cytokines decreased ROMK-1 expression. Inhibition of JNK/p38 had no effect on cytokine-induced down regulation of ROMK-1. Conclusion: Inhibition of JNK decreases proinflammatory cytokines and increases renal ROMK1 in sepsis. The latter is not due to an effect on the renal level but likely on the level of macrophages.
Glacial Survival of Boreal Trees in Northern Scandinavia

Tree Refugia Ideas of how and when boreal plants spread to the formerly glaciated parts of the world following the retreat of the glaciers 9000 years ago are long debated. Models of the postglacial spread of boreal plants argue for dispersal from southern refugia; however, Parducci et al. (p. 1083) have shown that both spruce and pine were present in small ice-free regions of Scandinavia much earlier than thought. DNA haplotyping confirmed that a remnant mitochondrial type of spruce, once unique to Scandinavia, now lives alongside the more common spruce originating from Eastern Europe. Evidence from lake cores collected from central and northern Norway indicated the survival of conifers as early as 22,000 years before the present, when apart from ice-free pockets, most of Scandinavia was covered by ice. DNA from modern and ancient spruce and pine indicate that both survived in ice-free areas during the last glaciations. It is commonly believed that trees were absent in Scandinavia during the last glaciation and first recolonized the Scandinavian Peninsula with the retreat of its ice sheet some 9000 years ago. Here, we show the presence of a rare mitochondrial DNA haplotype of spruce that appears unique to Scandinavia and with its highest frequency to the west—an area believed to sustain ice-free refugia during most of the last ice age. We further show the survival of DNA from this haplotype in lake sediments and pollen of Trøndelag in central Norway dating back ~10,300 years and chloroplast DNA of pine and spruce in lake sediments adjacent to the ice-free Andøya refugium in northwestern Norway as early as ~22,000 and 17,700 years ago, respectively. Our findings imply that conifer trees survived in ice-free refugia of Scandinavia during the last glaciation, challenging current views on survival and spread of trees as a response to climate changes.
Influence of misfit on the occurrence of veneering porcelain fractures (chipping) in implant‐supported metal‐ceramic fixed dental prostheses: an in vitro pilot trial

OBJECTIVE Technical complications such as veneer fractures are more common in implant-supported than tooth-supported restorations. The underlying causes have not been fully identified. The aim of this study was to evaluate whether misfit between the restoration and the implant may affect the risk of veneer fractures. MATERIALS AND METHODS Twenty standardized five-unit implant-supported metal-ceramic fixed dental prostheses (FDP)s were manufactured and fixed in acrylic blocks. The test group consisted of ten FDPs fixed with a 150-μm misfit at the distal abutment. The remaining ten FDPs were fixed without misfit and acted as a control group. All FDPS underwent cyclic loading for a total of 100,000 cycles at 30-300 N. The FDPs were checked for cracks or chip-off fractures regularly. After cyclic load, the retorque value of all abutment screws was checked. RESULTS Cracks within the veneering porcelain were noted in nine FDPs in the test group and one FDP in the control group. This difference was statistically significant (P < 0.001). Fractures of the veneering porcelain occurred in three FDPs in the test group. No fractures occurred in the control group. This difference was not statistically significant. There were no significant differences in retorque values neither between the groups nor between different abutment positions in the FDPs. CONCLUSIONS Within the limitations of this in vitro pilot trial, it is suggested that misfit between a restoration and the supporting implant may increase the risk of cracking and/or chipping of the veneering porcelain for metal-ceramic FDPs.