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991.
Diana L. Cousminer Jaakko T. Leinonen Antti-Pekka Sarin Himanshu Chheda Ida Surakka Karoliina Wehkalampi Pekka Ellonen Samuli Ripatti Leo Dunkel Aarno Palotie Elisabeth Widén 《PloS one》2015,10(6)
Constitutional delay of growth and puberty (CDGP) is the most common cause of pubertal delay. CDGP is defined as the proportion of the normal population who experience pubertal onset at least 2 SD later than the population mean, representing 2.3% of all adolescents. While adolescents with CDGP spontaneously enter puberty, they are at risk for short stature, decreased bone mineral density, and psychosocial problems. Genetic factors contribute heavily to the timing of puberty, but the vast majority of CDGP cases remain biologically unexplained, and there is no definitive test to distinguish CDGP from pathological absence of puberty during adolescence. Recently, we published a study identifying significant linkage between a locus at the pericentromeric region of chromosome 2 (chr 2) and CDGP in Finnish families. To investigate this region for causal variation, we sequenced chr 2 between the genomic coordinates of 79–124 Mb (genome build GRCh37) in the proband and affected parent of the 13 families contributing most to this linkage signal. One gene, DNAH6, harbored 6 protein-altering low-frequency variants (< 6% in the Finnish population) in 10 of the CDGP probands. We sequenced an additional 135 unrelated Finnish CDGP subjects and utilized the unique Sequencing Initiative Suomi (SISu) population reference exome set to show that while 5 of these variants were present in the CDGP set, they were also present in the Finnish population at similar frequencies. Additional variants in the targeted region could not be prioritized for follow-up, possibly due to gaps in sequencing coverage or lack of functional knowledge of non-genic genomic regions. Thus, despite having a well-characterized sample collection from a genetically homogeneous population with a large population-based reference sequence dataset, we were unable to pinpoint variation in the linked region predisposing delayed puberty. This study highlights the difficulties of detecting genetic variants under linkage regions for complex traits and suggests that advancements in annotation of gene function and regulatory regions of the genome will be critical for solving the genetic background of complex phenotypes like CDGP. 相似文献
992.
Christian Daugaard Peters Krista Dybtved Kjaergaard Jens Dam Jensen Kent Lodberg Christensen Charlotte Strandhave Ida Noerager Tietze Marija Kristina Novosel Bo Martin Bibby Bente Jespersen 《PloS one》2015,10(6)
Background and Aim
Little is known about the tolerability of antihypertensive drugs during hemodialysis treatment. The present study evaluated the use of the angiotensin II receptor blocker (ARB) irbesartan.Design
Randomized, double-blind, placebo-controlled, one-year intervention trial.Setting and Participants
Eighty-two hemodialysis patients with urine output >300 mL/day and dialysis vintage <1 year.Intervention
Irbesartan/placebo 300 mg/day for 12 months administered as add-on to antihypertensive treatment using a predialytic systolic blood pressure target of 140 mmHg in all patients.Outcomes and Measurements
Cardiac output, stroke volume, central blood volume, total peripheral resistance, mean arterial blood pressure, and frequency of intradialytic hypotension.Results
At baseline, the groups were similar regarding age, comorbidity, blood pressure, antihypertensive medication, ultrafiltration volume, and dialysis parameters. Over the one-year period, predialytic systolic blood pressure decreased significantly, but similarly in both groups. Mean start and mean end cardiac output, stroke volume, total peripheral resistance, heart rate, and mean arterial pressure were stable and similar in the two groups, whereas central blood volume increased slightly but similarly over time. The mean hemodynamic response observed during a dialysis session was a drop in cardiac output, in stroke volume, in mean arterial pressure, and in central blood volume, whereas heart rate increased. Total peripheral resistance did not change significantly. Overall, this pattern remained stable over time in both groups and was uninfluenced by ARB treatment. The total number of intradialytic hypotensive episodes was (placebo/ARB) 50/63 (P = 0.4). Ultrafiltration volume, left ventricular mass index, plasma albumin, and change in intradialytic total peripheral resistance were significantly associated with intradialytic hypotension in a multivariate logistic regression analysis based on baseline parameters.Conclusion
Use of the ARB irbesartan as an add-on to other antihypertensive therapy did not significantly affect intradialytic hemodynamics, neither in short nor long-term, and no significant increase in hypotensive episodes was seen.Trial registration
Clinicaltrials.gov NCT00791830 相似文献993.
The visual system is tuned for rapid detection of faces, with the fastest choice saccade to a face at 100ms. Familiar faces have a more robust representation than do unfamiliar faces, and are detected faster in the absence of awareness and with reduced attentional resources. Faces of family and close friends become familiar over a protracted period involving learning the unique visual appearance, including a view-invariant representation, as well as person knowledge. We investigated the effect of personal familiarity on the earliest stages of face processing by using a saccadic-choice task to measure how fast familiar face detection can happen. Subjects made correct and reliable saccades to familiar faces when unfamiliar faces were distractors at 180ms—very rapid saccades that are 30 to 70ms earlier than the earliest evoked potential modulated by familiarity. By contrast, accuracy of saccades to unfamiliar faces with familiar faces as distractors did not exceed chance. Saccades to faces with object distractors were even faster (110 to 120 ms) and equivalent for familiar and unfamiliar faces, indicating that familiarity does not affect ultra-rapid saccades. We propose that detectors of diagnostic facial features for familiar faces develop in visual cortices through learning and allow rapid detection that precedes explicit recognition of identity. 相似文献
994.
995.
Heloisa da Silveira Paro Pedro Susilene Maria Tonelli Nardi Maria Izabel Ferreira Pereira Rosangela Siqueira Oliveira Philip Noel Suffys Harrison Magdinier Gomes Amanda Juliane Finardi Eloise Brasil de Moraes Ida Maria Foschiani Dias Baptista Ricardo Luiz Dantas Machado Lilian Castiglioni 《Memórias do Instituto Oswaldo Cruz》2015,110(2):235-248
Drug-resistant tuberculosis (TB) is a growing global threat. Approximately 450,000
people developed multidrug-resistant TB worldwide in 2012 and an estimated 170,000
people died from the disease. This paper describes the sociodemographic,
clinical-epidemiological and bacteriological aspects of TB and correlates these
features with the distribution of anti-TB drug resistance. Mycobacterium tuberculosis
(MT) cultures and drug susceptibility testing were performed according to the BACTEC
MGIT 960 method. The results demonstrated that MT strains from individuals who
received treatment for TB and people who were infected with human immunodeficiency
virus were more resistant to TB drugs compared to other individuals (p < 0.05).
Approximately half of the individuals received supervised treatment, but most
drug-resistant cases were positive for pulmonary TB and exhibited positive acid-fast
bacilli smears, which are complicating factors for TB control programs. Primary
healthcare is the ideal level for early disease detection, but tertiary healthcare is
the most common entry point for patients into the system. These factors require
special attention from healthcare managers and professionals to effectively control
and monitor the spread of TB drug-resistant cases. 相似文献
996.
997.
Background
The purpose of this study was to evaluate the coherence between three different methods assessing the power driven from a counter movement jump (CMJ); the Powertimer 300-series contact mat (C-mat), the MuscleLab 4010 infrared mat (IR-mat) and the MuscleLab 4010 linear encoder (M-encoder), and to evaluate the test-retest reliability of the M-encoder.Methods
Twenty-two males and 29 female, elite athletes performed two test sessions with three days in between. Each test session included counter movement jumps (CMJ) performed on a Smith-machine with external loads of 40 kg. Jump height and flight time were assessed with C-mat and IR-mat, and power was additionally assessed with C-mat. Variables analyzed from the M-encoder were average power (AP), average force (AV), average velocity (AV), and distance (D).Results
The results from the C-mat were systematically higher than the ones obtained from the M-encoder and IR-mat. The correlation between the C-mat, M-encoder and the IR-mat was strong (rp?=?0.95-0.98). The results showed a high test-retest reliability for all indices assessed with the M-encoder, AP (rp?=?0.97, p?<?0.001; TE%?=?3.9%), AF (rp?=?0.99, p?<?0.001; TE%?=?1.4%). Furthermore, the AV had high values (rp?=?0.94, p?<?0.001; TE%?=?2.9%) as well as D (rp?=?0.87, p?<?0.001; TE%?=?5.4%).Conclusion
It is important to use the same equipment in both pre- and post-testing, since all three methods were reliable, coherent but not interchangeable to each other.998.
999.
Ida Engqvist Katja Wyss Charlotte Asker-Hagelberg Ulf Bergman Ingegerd Odar-Cederl?f Carl-Olav Stiller Jessica Fryckstedt 《PloS one》2015,10(6)