Miracle-dz/UniFAR-FTUs huggingface dataset:
Modified Citrus Pectin Prevents Blood-Brain Barrier Disruption in Mouse Subarachnoid Hemorrhage by Inhibiting Galectin-3

Background and Purpose— Plasma levels of galectin-3—a matricellular protein—are increased after aneurysmal subarachnoid hemorrhage (SAH), but the functional significance remains undetermined. This study was conducted to evaluate whether modified citrus pectin (MCP; galectin-3 inhibitor) prevents post-SAH early brain injury, focusing on blood-brain barrier disruption. Methods— C57BL/6 male adult mice (n=251) underwent sham or filament perforation SAH modeling, followed by a random intracerebroventricular injection of vehicle or drug at 30 minutes post-modeling. First, vehicle-treated and 0.8, 4, 16, or 32 µg MCP-treated mice were assessed by neuroscore and brain water content at 24 and 48 hours post-modeling. Second, Evans blue extravasation, Western blotting, coimmunoprecipitation and immunostaining were performed in vehicle-treated or 4 µg MCP-treated mice at 24 hours post-modeling. Third, vehicle or R-galectin-3 (recombinant galectin-3) was administered to SAH mice simultaneously with vehicle or MCP, and neuroscore and Evans blue extravasation were evaluated at 24 hours post-modeling. Fourth, vehicle or R-galectin-3 was administered to MCP-treated SAH mice at 24 hours, and neuroscore and IgG immunostaining were evaluated at 48 hours post-SAH. Results— Among tested dosages, 4 µg MCP showed the best neuroprotective effects as to preventing neurological impairments and brain edema at 24 to 48 hours post-SAH. Four micrograms MCP attenuated post-SAH blood-brain barrier disruption and galectin-3 upregulation in brain capillary endothelial cells, associated with inactivation of ERK (extracellular signal-related kinase) 1/2, STAT (signal transducer and activator of transcription)-3, and MMP (matrix metalloproteinase)-9, and the consequent preservation of a tight junction protein ZO-1 (zonula occludens-1). Coimmunoprecipitation assay demonstrated physical interactions between galectin-3 and TLR (Toll-like receptor) 4. R-galectin-3 blocked the neuroprotective effects of MCP. Conclusions— MCP prevents post-SAH blood-brain barrier disruption possibly by inhibiting galectin-3, of which the mechanisms may include binding to TLR4 and activating ERK1/2, STAT-3, and MMP-9. This study suggests galectin-3 to be a novel therapeutic target against post-SAH early brain injury.
Determination of adjusted reference intervals of urinary biomarkers of oxidative stress in healthy adults using GAMLSS models

In this study we aimed at identifying main demographic, laboratory and environmental factors influencing the level of urinary biomarkers (DNA-derived 8-oxodG and lipid membrane-derived 8-isoprostane), and deriving their adjusted 95% reference intervals (RI) in a sample of healthy people from the general population. Data from 281 healthy subjects from the Gene Environment Interactions in Respiratory Diseases survey were used in this study. Generalized additive models for location, scale and shape (GAMLSS) were used to find determinants of the biomarkers among gender, age, season and distance from collection (DFC), and to predict their RI. The RI of the biomarkers stratified by season and adjusted for DFC showed a slight statistically significant decrease in the biomarkers at the increasing DFC in two seasons, except the 8-oxodG during the warm season: median levels at the min and max values of DFC were (ng/mgcreat) 7.0–1.1 in the cold and 3.9–3.9 in the warm seasons for 8-oxodG, 0.7–0.2 in the cold and 1.3–0.6 in the warm seasons for 8-isoprostane. Both the biomarkers should be evaluated in association with the DFC and season in large epidemiological studies. The (semi)parametric GAMLSS method is a useful and flexible technique, which makes it possible to estimate adjusted RI.
Sprint-Specific Training in Youth: Backward Running vs. Forward Running Training on Speed and Power Measures in Adolescent Male Athletes.

Uthoff, A, Oliver, J, Cronin, J, Harrison, C, and Winwood, P. Sprint-specific training in youth: Backward running vs. forward running training on speed and power measures in adolescent male athletes. J Strength Cond Res XX(X): 000-000, 2018-This study compared the effects of 2 sprint-specific training programs against the natural development of speed, power, and stiffness in a group of adolescent male athletes. Forty-three male adolescents (aged 13-15 years) were randomly assigned to 1 of 2 training groups; backward running training (BRT = 26), or forward running training (FRT = 17). A physical education class (n = 24) of similar age constituted a control (CON) group. Both training groups performed running sessions matched for distance and intensity biweekly for 8 weeks. Parametric and magnitude-based inferences were used to analyze within group (pre-post measures) and between group (gain scores) for 10-m, 10- to 20-m, and 20-m sprint times, vertical countermovement jump (CMJ) height, and vertical leg stiffness. Both running groups significantly improved (p ≤ 0.05) in all performance tests from pre-training to post-training, with effect sizes ranging from -1.25 to 0.63. When the groups were compared, the BRT and FRT groups improved significantly (p ≤ 0.01) on all sprint performances and stiffness relative to the CON group. The BRT group demonstrated favorable effects for 10-m and 20-m sprint performances (effect size [ES] = -0.47 and -0.26, respectively) and CMJ height (ES = 0.51) compared with the FRT group. These results demonstrate that forward and backward sprint-specific training programs enhance speed and power measures more than natural development in adolescent male athletes. Furthermore, the greater training responses in sprint performance and CMJ ability indicate that BRT is a useful tool for improving concentric strength and power and may be classified as a sprint-specific training method.
Comparison of stents used for endovascular treatment of intracranial aneurysms

ABSTRACT Introduction: Stent-assisted coiling (SAC) has widened indications of endovascular treatment of intracranial aneurysms (wide-neck, fusiform aneurysms); moreover, it is associated with more stable anatomical results. Besides the development of other techniques such as flow diverter stents, bifurcation stents, or intrasaccular flow disruptors, SAC remains one of the most used endovascular techniques because it provides good clinical and anatomical results for most aneurysms. Several devices based on the same principle are available and have undergone many adaptations and developments over 20 years of intracranial stenting. Areas covered: The purpose of this article is to review and compare intrinsic properties of available devices and their anatomical and clinical performance. Expert commentary: Based on this review and our experience of SAC, we will discuss the behavior and performance of those devices in different anatomic and clinical situations.
Pheochromocytoma in Congenital Cyanotic Heart Disease

Studies on genome-wide transcription patterns have shown that many genetic alterations implicated in pheochromocytoma-paraganglioma (P-PGL) syndromes cluster in a common cellular pathway leading to aberrant activation of molecular response to hypoxia in normoxic conditions (the pseudohypoxia hypothesis). Several cases of P-PGL have been reported in patients with cyanotic congenital heart disease (CCHD). Patients affected with CCHD have an increased likelihood of P-PGL compared to those affected with noncyanotic congenital heart disease. One widely supported hypothesis is that chronic hypoxia represents the determining factor supporting this increased risk. We report the case of a 23-year-old woman affected with congenital tricuspid atresia surgically by the Fontan procedure. The patient was admitted to hospital with hypertensive crisis and dyspnea. Chest computed tomography revealed, incidentally, a 6-cm mass in the left adrenal lodge. Increased levels of noradrenaline (NA) and its metabolites were detected (plasma NA 5003.7 pg/ml, n.v.<480; urinary NA 1059.5 µg/24 h, n.v.<85.5; urinary metanephrine 489 µg/24 h, n.v.<320). The patient did not report any additional symptom related to catecholamine excess. The left adrenal tumor showed abnormal accumulation when 131I-metaiodobenzylguanidine scintigraphy was performed. A 18F-fluorodeoxyglucose positron emission tomography showed no significant metabolic activity in the left adrenal gland but intense uptake in the supra- and subdiaphragmatic brown adipose tissue, probably due to noradrenergic-stimulated glucose uptake. The patient underwent left open adrenalectomy after preconditioning with α- and β-blockers and histopathological examination confirmed the diagnosis of pheochromocytoma (Ki-67<5%). Screening for germline mutations did not show any genes mutation (investigated mutations: RET, TMEM127, MAX, SDHD, SDHC, SDHB, SDHAF2, SDHA, and VHL). Clinicians should consider P-PGL when an unexplained clinical deterioration occurs in CCHD patients, even in the absence of typical paroxysmal symptoms.
How the intracellular partitioning of tRNA and tRNA modification enzymes affects mitochondrial function

Organisms have evolved different strategies to seclude certain molecules to specific locations of the cell. This is most pronounced in eukaryotes with their extensive intracellular membrane systems. Intracellular compartmentalization is particularly critical in genome containing organelles, which because of their bacterial evolutionary ancestry still maintain protein‐synthesis machinery that resembles more their evolutionary origin than the extant eukaryotic cell they once joined as an endosymbiont. Despite this, it is clear that genome‐containing organelles such as the mitochondria are not in isolation and many molecules make it across the mitochondrial membranes from the cytoplasm. In this realm the import of tRNAs and the enzymes that modify them prove most consequential. In this review, we discuss two recent examples of how modifications typically found in cytoplasmic tRNAs affect mitochondrial translation in organisms that forcibly import all their tRNAs from the cytoplasm. In our view, the combination of tRNA import and the compartmentalization of modification enzymes must have played a critical role in the evolution of the organelle. © 2018 IUBMB Life, 70(12):1207–1213, 2018
Proteins in the periplasmic space and outer membrane vesicles of Rhizobium etli CE3 grown in minimal medium are largely distinct and change with growth phase

Rhizobium etli CE3 grown in succinate-ammonium minimal medium (MM) excreted outer membrane vesicles (OMVs) with diameters of 40 to 100 nm. Proteins from the OMVs and the periplasmic space were isolated from 6 and 24 h cultures and identified by proteome analysis. A total 770 proteins were identified: 73.8 and 21.3 % of these proteins occurred only in the periplasm and OMVs, respectively, and only 4.9 % were found in both locations. The majority of proteins found in either location were present only at 6 or 24 h: in the periplasm and OMVs, only 24 and 9 % of proteins, respectively, were present at both sampling times, indicating a time-dependent differential sorting of proteins into the two compartments. The OMVs contained proteins with physiologically varied roles, including Rhizobium adhering proteins (Rap), polysaccharidases, polysaccharide export proteins, autoaggregation and adherence proteins, glycosyl transferases, peptidoglycan binding and cross-linking enzymes, potential cell wall modifying enzymes, porins, multidrug efflux RND family proteins, ABC transporter proteins, and heat shock proteins. As expected, proteins with known periplasmic localizations (phosphatases, phosphodiesterases, pyrophosphatases) were found only in the periplasm, along with numerous proteins involved in amino acid and carbohydrate metabolism and transport. Nearly one-quarter of the proteins present in the OMVs were also found in our previous analysis of the R. etli total exproteome of MM-grown cells, indicating that these nanoparticles are an important mechanism for protein excretion in this species. IMPORTANCE The reduction of atmospheric nitrogen to ammonia by rhizobia symbiotically associated with legumes is of major importance in sustainable agricultural. Rhizobia excrete a variety of symbiotically important proteins using canonical secretion systems. In this work, we show that Rhizobium etli grown in culture also excretes proteins in membrane-enclosed structures called outer membrane vesicles (OMVs). This study reports OMV production by rhizobia. Proteins identified in the OMVs included Rhizobium adhering (Rap) and autoaggregation proteins, polysaccharidases, RTX toxins, porins and multidrug efflux proteins. Some of these proteins have important roles in the R. etli-common bean symbiosis, and their packaging into OMVs could deliver them to the environment in a concentrated yet diffusible form protected from degradation. The work described here provides a basis for future studies on the function of rhizobial OMVs in free life and symbiosis.
Shortened Lifespan and Other Age-Related Defects in Bang Sensitive Mutants of Drosophila melanogaster

Mitochondrial diseases are complex disorders that exhibit their primary effects in energetically active tissues. Damage generated by mitochondria is also thought to be a key component of aging and age-related disease. An important model for mitochondrial dysfunction is the bang sensitive (bs) mutants in Drosophila melanogaster. Although these mutants all show a striking seizure phenotype, several bs mutants have gene products that are involved with mitochondrial function, while others affect excitability another way. All of the bs mutants (parabss, eas, jus, ses B, tko are examined here) paralyze and seize upon challenge with a sensory stimulus, most notably mechanical stimulation. These and other excitability mutants have been linked to neurodegeneration with age. In addition to these phenotypes, we have found age-related defects for several of the bs strains. The mutants eas, ses B, and tko display shortened lifespan, an increased mean recovery time from seizure with age, and decreased climbing ability over lifespan as compared to isogenic CS or w1118 lines. Other mutants show a subset of these defects. The age-related phenotypes can be rescued by feeding melatonin, an antioxidant, in all the mutants except ses B. The age-related defects do not appear to be correlated with the seizure phenotype. Inducing seizures on a daily basis did not exacerbate the phenotypes and treatment with antiepileptic drugs did not increase lifespan. The results suggest that the excitability phenotypes and the age-related phenotypes may be somewhat independent and that these phenotypes mutants may arise from impacts on different pathways.
Pediatric Dosing of Ganciclovir and Valganciclovir: How Model‐Based Simulations Can Prevent Underexposure and Potential Treatment Failure

Intravenous ganciclovir and oral valganciclovir are effective in the prevention and treatment of pediatric cytomegalovirus (CMV) infection but various dosing regimens are used in medical practice. Population pharmacokinetic (PopPK) model‐based simulations were used to propose a new ganciclovir pediatric dosing algorithm for regulatory review and to evaluate the approved valganciclovir pediatric dosing algorithm against published dosing recommendations derived from quantitative approaches. Oral valganciclovir (mg = 7 × body surface area (BSA) × creatinine clearance according to the Schwarz formula (CrCLS) daily) and i.v. ganciclovir (mg = 3 × BSA × CrCLS daily) are effective in reaching ganciclovir target exposure for the prevention of CMV (area under the concentration‐time curve (AUC)0–24 40–60 μg ∙ hour/mL) in most pediatric patients across the full pediatric age range. In contrast, ganciclovir and valganciclovir dosing based on body weight, as commonly used in medical practice, leads to underexposure, particularly in younger pediatric patients. This example shows that model‐based dosing algorithms built on clinical pharmacology and implemented using good modeling practice can prevent underexposure and reduce the risk of treatment failure in pediatric patients.
A “Buildup” of Speech Intelligibility in Listeners With Normal Hearing and Hearing Loss

The perception of simple auditory mixtures is known to evolve over time. For instance, a common example of this is the “buildup” of stream segregation that is observed for sequences of tones alternating in pitch. Yet very little is known about how the perception of more complicated auditory scenes, such as multitalker mixtures, changes over time. Previous data are consistent with the idea that the ability to segregate a target talker from competing sounds improves rapidly when stable cues are available, which leads to improvements in speech intelligibility. This study examined the time course of this buildup in listeners with normal and impaired hearing. Five simultaneous sequences of digits, varying in length from three to six digits, were presented from five locations in the horizontal plane. A synchronized visual cue at one location indicated which sequence was the target on each trial. We observed a buildup in digit identification performance, driven primarily by reductions in confusions between the target and the maskers, that occurred over the course of three to four digits. Performance tended to be poorer in listeners with hearing loss; however, there was only weak evidence that the buildup was diminished or slowed in this group.
Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination

Background Pneumococcal conjugate vaccines (PCVs) have the potential to prevent pneumococcal disease through direct and indirect protection. This multicentre European study estimated the indirect effects of 5-year childhood PCV10 and/or PCV13 programmes on invasive pneumococcal disease (IPD) in older adults across 13 sites in 10 European countries, to support decision-making on pneumococcal vaccination policies. Methods For each site we calculated IPD incidence rate ratios (IRR) in people aged ≥65 years by serotype for each PCV10/13 year (2011–2015) compared with 2009 (pre-PCV10/13). We calculated pooled IRR and 95% CI using random-effects meta-analysis and PCV10/13 effect as (1 − IRR)*100. Results After five PCV10/13 years, the incidence of IPD caused by all types, PCV7 and additional PCV13 serotypes declined 9% (95% CI −4% to 19%), 77% (95% CI 67% to 84%) and 38% (95% CI 19% to 53%), respectively, while the incidence of non-PCV13 serotypes increased 63% (95% CI 39% to 91%). The incidence of serotypes included in PCV13 and not in PCV10 decreased 37% (95% CI 22% to 50%) in six PCV13 sites and increased by 50% (95% CI −8% to 146%) in the four sites using PCV10 (alone or with PCV13). In 2015, PCV13 serotypes represented 20–29% and 32–53% of IPD cases in PCV13 and PCV10 sites, respectively. Conclusion Overall IPD incidence in older adults decreased moderately after five childhood PCV10/13 years in 13 European sites. Large declines in PCV10/13 serotype IPD, due to the indirect effect of childhood vaccination, were countered by increases in non-PCV13 IPD, but these declines varied according to the childhood vaccine used. Decision-making on pneumococcal vaccination for older adults must consider the indirect effects of childhood PCV programmes. Sustained monitoring of IPD epidemiology is imperative.
Seroprevalence of Malaria and Hepatitis B Coinfection among Pregnant Women in Tamale Metropolis of Ghana: A Cross-Sectional Study

Background Coinfections are becoming common risk factors that may contribute to the increased burden of morbidity in pregnancy. The aim of this study was to assess the seroprevalence of coinfections of malaria, hepatitis B (HBV), human immunodeficiency virus (HIV), and syphilis among pregnant women attending antenatal clinics (ANC) in the Tamale Metropolis. Methods By means of rapid diagnostic tests (RDTs), pregnant women attending the Tamale Teaching Hospital (TTH) were screened for malaria, HBV infection, HIV infection, and syphilis from March 2013 to February 2015. Haemoglobin (Hb) values, sickling, and glucose-6-phosphate dehydrogenase deficiency (G6PDd) statuses were also assessed using full blood count (FBC), sodium metabisulphite, and methaemoglobin reduction tests, respectively. Logistic regression analysis was performed to estimate the risks/odds ratios (ORs) for the coinfections and other variables (age, gravidity, and time of the first ANC visit) with 95% confidence intervals (CIs) and set p values for accepting any differences at <0.05. Results Within the two-year study period, data were collected from 3,127 pregnant women. The mean age (SD) of the pregnant women was 28.5 (±5.0) years. Of the total number, seroprevalence was high for malaria (11.6%) and HBV infection (4.2%) and low for HIV infection (1.0%) and syphilis (0.4%) monoinfections. Mal/HBV coinfection was higher (0.7%) when compared with Mal/HIV (0.1%), Mal/syphilis (0.0%), HBV/HIV (0.0%), HBV/syphilis (0.1%), and HIV/syphilis (0.0%) coinfections. The mean Hb (g/dl) for the women with the four monoinfections was significantly different from one another (p=0.009). Pregnant women with malaria infection were about 2 times more likely to be coinfected with HBV even after adjusting for potential confounders (adjusted odds ratio (AOR) = 1.66, 95% CI = 1.04–2.65, p=0.031). Those in their third trimester and visiting the ANC for the first time were significantly less likely to be infected with HBV (AOR = 0.45, 95% CI = 0.28–0.73, p=0.001), with malaria/HBV coinfection (AOR = 0.09, 95% CI = 0.01–0.68, p=0.020), and with any coinfection (AOR = 0.19, 95% CI = 0.06–0.63, p=0.007). Conclusion A comparatively high seroprevalence of malaria and its coinfection with HBV in pregnant women was observed in this study. Considering the effects that both malaria and HBV have on the liver, it would be expedient to conduct further studies to assess liver function among malaria/HBV-infected individuals, while interventions to prevent coinfections among pregnant women are intensified.
Informative group testing for multiplex assays

Infectious disease testing frequently takes advantage of two tools—group testing and multiplex assays—to make testing timely and cost effective. Until the work of Tebbs et al. (2013) and Hou et al. (2017), there was no research available to understand how best to apply these tools simultaneously. This recent work focused on applications where each individual is considered to be identical in terms of the probability of disease. However, risk‐factor information, such as past behavior and presence of symptoms, is very often available on each individual to allow one to estimate individual‐specific probabilities. The purpose of our paper is to propose the first group testing algorithms for multiplex assays that take advantage of individual risk‐factor information as expressed by these probabilities. We show that our methods significantly reduce the number of tests required while preserving accuracy. Throughout this paper, we focus on applying our methods with the Aptima Combo 2 Assay that is used worldwide for chlamydia and gonorrhea screening.