Background Characteristics of cohorts of individuals aged ≤17 years with homeostatic iron regulator (
) p.C282Y (rs1800562) homozygosity, a common hemochromatosis genotype, have not been reported. ...Methodology We retrospectively tabulated characteristics of white individuals aged ≤17 years with p.C282Y homozygosity. Individuals were not recruited for this study. We defined transferrin saturation (TS) >45%, serum ferritin (SF) >300 µg/L (M) and >200 µg/L (F) as elevated and liver iron grade 3 or 4, hepatic iron index >1.9 µmol Fe/g dry weight liver/y, and phlebotomy-mobilized iron >1.0 g (M) and >0.3 g (F) as increased. Results There were nine males and six females with a mean age of 12 ± 4 years (range = 5-17 years). The mean age of 10 probands (13 ± 3 years) was greater than that of five individuals discovered in family studies (9 ± 4 years) (p = 0.0403). Presenting manifestations of probands included fatigue/lethargy (5), elevated TS (2), and polycystic ovary syndrome, amenorrhea, and diabetes (2). In 15 individuals, the mean TS was 65 ± 23%. TS was elevated in 11 (73.3%) individuals aged 5-17 years. In 14 individuals, the mean SF was 262 ± 289 µg/L. SF was elevated and liver and phlebotomy-mobilized iron were increased in two male and three female probands aged 13-16 years (5/14 individuals, 35.7%). No individual had advanced hepatic fibrosis, arthropathy, hypogonadism, cardiomyopathy, or hyperpigmentation. Conclusions We conclude that five individuals aged 13-16 years (5/14 individuals, 35.7%) had increased liver and phlebotomy-mobilized iron.
Numerous studies have shown that the relative frequency of retouched pieces can help to distinguish forager mobility strategies amongst individual layers at a single site and, potentially, at ...multiple sites across regions (Riel-Salvatore & Barton, 2004; Riel-Salvatore et al., 2008; Barton & Riel-Salvatore, 2014). We use this proxy measure and other lines of evidence to evaluate Late Pleistocene human land-use practices from 47 Upper Paleolithic and Mesolithic sites in northern coastal Spain.
To monitor mobility strategies we examine the proportion of retouched pieces to total lithics, focusing on backed pieces which probably served mostly as replaceable inserts in organic armatures for hunting weapons. Kuhn (1995) argued that foragers at some distance from a residential base would have had to rely on replaceable elements for the tools and weapons they carried with them. Assemblages with low total lithic densities but a high proportion of backed pieces would most likely represent the remains of short-term camps where hunting weapons were repaired in the field, whereas those with high lithic densities and relatively few backed pieces would likely represent residential bases where hunting weapons were manufactured.
The analysis also links variation in lithic assemblages to paleoclimate and topography and uses 951 radiocarbon dates to identify demographic ‘pulses’ under the assumption that – ceteris paribus – the density of dates and the density of population are at least roughly linearly correlated with one another (French & Collins, 2015). Increases and decreases in regional population density can be detected and compared to episodes of climate change measured by the GISP2 and NGRIP2 ice cores over the Pleniglacial, Tardiglacial (MIS 2) and the early Holocene. Data insufficiencies, incomparable typologies, and adequacy of reporting are also discussed.
Abstract
As the global climate warms, a key question is how increased leaf temperatures will affect tree physiology and the coupling between leaf and air temperatures in forests. To explore the ...impact of increasing temperatures on plant performance in open air, we warmed leaves in the canopy of two mature evergreen forests, a temperate Eucalyptus woodland and a tropical rainforest. The leaf heaters consistently maintained leaves at a target of 4 °C above ambient leaf temperatures. Ambient leaf temperatures (Tleaf) were mostly coupled to air temperatures (Tair), but at times, leaves could be 8–10 °C warmer than ambient air temperatures, especially in full sun. At both sites, Tleaf was warmer at higher air temperatures (Tair > 25 °C), but was cooler at lower Tair, contrary to the ‘leaf homeothermy hypothesis’. Warmed leaves showed significantly lower stomatal conductance (−0.05 mol m−2 s−1 or −43% across species) and net photosynthesis (−3.91 μmol m−2 s−1 or −39%), with similar rates in leaf respiration rates at a common temperature (no acclimation). Increased canopy leaf temperatures due to future warming could reduce carbon assimilation via reduced photosynthesis in these forests, potentially weakening the land carbon sink in tropical and temperate forests.
Graphical abstract
To report outcomes across three countries for patients with symptomatic knee or hip OA attending the evidence-based education and exercise therapy program Good Life with osteoArthritis from Denmark ...(GLA:D®).
GLA:D® is a structured treatment program including 2–3 patient education sessions and 12 supervised exercise sessions delivered over 8 weeks by certified health care practitioners. The program was introduced in Denmark in 2013, in Canada 2015 and in Australia 2016. Absolute mean change in pain intensity, number of chair stands in 30 s, 40 m walk test time and Knee injury and Osteoarthritis Outcome Score (KOOS)/Hip dysfunction and Osteoarthritis Outcome Score (HOOS) QOL subscale scores from baseline to immediately after treatment were reported as means and 95 % CIs and proportion of responders for each country.
Patients from the three countries improved 26–33% in mean pain intensity, 8–12% in walking speed, 18–30% in chair stand ability and 12–26% in joint-related quality of life from baseline to immediately after treatment, with no clinically relevant differences between patients with hip and knee OA. These improvements correspond with moderate to large within-group effect sizes and 43–47 % of the patients experienced clinically relevant pain reductions.
About half or more of patients across the three countries were categorized as responders for pain and objective function following the implementation of GLA:D®. These findings indicate positive patient outcomes associated with GLA:D® participation across varying health care systems from implementation of guideline-based patient education and exercise therapy for knee and hip OA.
The bromodomain containing proteins TRIM24 (tripartite motif containing protein 24) and BRPF1 (bromodomain and PHD finger containing protein 1) are involved in the epigenetic regulation of gene ...expression and have been implicated in human cancer. Overexpression of TRIM24 correlates with poor patient prognosis, and BRPF1 is a scaffolding protein required for the assembly of histone acetyltransferase complexes, where the gene of MOZ (monocytic leukemia zinc finger protein) was first identified as a recurrent fusion partner in leukemia patients (8p11 chromosomal rearrangements). Here, we present the structure guided development of a series of N,N-dimethylbenzimidazolone bromodomain inhibitors through the iterative use of X-ray cocrystal structures. A unique binding mode enabled the design of a potent and selective inhibitor 8i (IACS-9571) with low nanomolar affinities for TRIM24 and BRPF1 (ITC K d = 31 nM and ITC K d = 14 nM, respectively). With its excellent cellular potency (EC50 = 50 nM) and favorable pharmacokinetic properties (F = 29%), 8i is a high-quality chemical probe for the evaluation of TRIM24 and/or BRPF1 bromodomain function in vitro and in vivo.
No global positioning system (GPS) technology study has been conducted among a sample of young gay, bisexual, and other men who have sex with men (YMSM). As such, the purpose of this study was to ...evaluate the feasibility and acceptability of using GPS methods to understand the spatial context of substance use and sexual risk behaviors among a sample of YMSM in New York City, a high-risk population.
Data came from a subsample of the ongoing P18 Cohort Study (n = 75). GPS feasibility and acceptability among participants was measured with: 1) a pre- and post-survey and 2) adherence to the GPS protocol which included returning the GPS device, self-report of charging and carrying the GPS device as well as objective data analyzed from the GPS devices. Analyses of the feasibility surveys were treated as repeated measures as each participant had a pre- and post-feasibility survey. When comparing the similar GPS survey items asked at baseline and at follow-up, we present percentages and associated p-values based on chi-square statistics.
Participants reported high ratings of pre-GPS acceptability, ease of use, and low levels of wear-related concerns in addition to few concerns related to safety, loss, or appearance, which were maintained after baseline GPS feasibility data collection. The GPS return rate was 100%. Most participants charged and carried the GPS device on most days. Of the total of 75 participants with GPS data, 75 (100%) have at least one hour of GPS data for one day and 63 (84%) had at least one hour on all 7 days.
Results from this pilot study demonstrate that utilizing GPS methods among YMSM is feasible and acceptable. GPS devices may be used in spatial epidemiology research in YMSM populations to understand place-based determinants of health such as substance use and sexual risk behaviors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
MicroRNAs (miRNAs) have important roles in diverse cellular processes, but little is known about their identity and functions during early mammalian development. Here, we show the effects of the loss ...of maternal inheritance of miRNAs following specific deletion of Dicer from growing oocytes. The mutant mature oocytes were almost entirely depleted of all miRNAs, and they failed to progress through the first cell division, probably because of disorganized spindle formation. By comparing single-cell cDNA microarray profiles of control and mutant oocytes, our data are compatible with the notion that a large proportion of the maternal genes are directly or indirectly under the control of miRNAs, which demonstrates that the maternal miRNAs are essential for the earliest stages of mouse embryonic development.
The equiatomic alloy FeRh is of great scientific and technological interest due its highly unusual first-order antiferromagnetic (AF) to ferromagnetic (FM) phase transition. Here we report an ...exploration of the interplay between topography and phase evolution with a comprehensive magnetic force microscopy study of nominal 50 nm thick FeRh thin films and subtractively patterned wires of width 0.2 µm-2 µm. In continuous films where the surface morphology had not been optimised for smoothness, the topographical variation was observed to dominate the distribution of the magnetic transition temperatures and dictates the nucleation and growth of the magnetic phases. This observation was repeated for patterned elements, where the effects of surface morphology were more significant than those of spatial confinement. These results have clear implications for future studies of low-dimensional FeRh films, as surface topography must be considered when analysing and comparing the transition behaviour of FeRh thin films.
Constrictive pericarditis in the new millennium Gillombardo, C. Barton; Hoit, Brian D.
Journal of cardiology,
April 2024, 2024-Apr, 2024-04-00, 20240401, Letnik:
83, Številka:
4
Journal Article
Recenzirano
Constrictive pericarditis (CP) is a complex clinical syndrome in which an inflamed pericardium becomes fibrotic and non-compliant, ultimately reducing cardiac pump performance. Although we have known ...about CP for centuries, it remains a challenge to diagnose. Recent advances in cardiac imaging, along with an expanding armamentarium of treatment options, have improved the quality and precision of care for patients with CP. This article reviews important historical and contemporary perspectives on the pathophysiology of CP, as well as our approach to diagnosis and management.
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•Loss of pericardial compliance and reserve volume are central to the pathophysiology of constrictive pericarditis.•Patient presentation, treatment, and prognosis are related to the extent of pericardial fibrosis.•Diagnosis may require integrating clinical data with cardiac imaging and invasive hemodynamics.•Transthoracic echocardiography remains the first-line imaging modality.•Cardiac magnetic resonance imaging and computed tomography can help confirm diagnosis and guide the next steps in management.
This study introduces a novel technique to implement a locking hole system into AM patient-specific implants without the need of additional post-processing steps such as mechanical machining. This ...has the potential to decrease the time and cost of manufacturing these implants, providing surgeons with an additional option, that is better suited in cases where the underlying bone is already weakened or bone porosis is an inherent risk. A commercially available locking system was chosen and replicated using high-resolution X-ray CT. A biocompatible material, 316L stainless steel was used to print specimen on a L-PBF machine in different orientations. The specimen were heat treated to tune the mechanical properties to enable the locking system to work. The accuracy of the printed holes was confirmed using a nominal/actual comparison between the original and printed holes. The strength of the system was evaluated by measuring the force needed to push the screw out of the locking plate. The 316L stainless steel samples, when annealed to tailor hardness, performed similarly to the commercial system. This included different build orientations that suggest the locking system can be included in AM implants without the need for additional post-processing steps.
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•A locking fixation system was printed in different orientations using L-PBF•The geometry of the printed system was compared to the original using X-ray CT•The mechanical properties of the used material was characterized•The strength of the printed system was compared to the original
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