•GALE is expressed during late-stage megakaryopoiesis, regulating the glycosylation and surface exposure of GPIbα and β1 integrin.•Novel GALE variants cause syndromic macrothrombocytopenia associated ...with impaired platelet formation and function.
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Glycosylation is recognized as a key process for proper megakaryopoiesis and platelet formation. The enzyme uridine diphosphate (UDP)-galactose-4-epimerase, encoded by GALE, is involved in galactose metabolism and protein glycosylation. Here, we studied 3 patients from 2 unrelated families who showed lifelong severe thrombocytopenia, bleeding diathesis, mental retardation, mitral valve prolapse, and jaundice. Whole-exome sequencing revealed 4 variants that affect GALE, 3 of those previously unreported (Pedigree A, p.Lys78ValfsX32 and p.Thr150Met; Pedigree B, p.Val128Met; and p.Leu223Pro). Platelet phenotype analysis showed giant and/or grey platelets, impaired platelet aggregation, and severely reduced alpha and dense granule secretion. Enzymatic activity of the UDP-galactose-4-epimerase enzyme was severely decreased in all patients. Immunoblotting of platelet lysates revealed reduced GALE protein levels, a significant decrease in N-acetyl-lactosamine (LacNAc), showing a hypoglycosylation pattern, reduced surface expression of gylcoprotein Ibα-IX-V (GPIbα-IX-V) complex and mature β1 integrin, and increased apoptosis. In vitro studies performed with patients-derived megakaryocytes showed normal ploidy and maturation but decreased proplatelet formation because of the impaired glycosylation of the GPIbα and β1 integrin, and reduced externalization to megakaryocyte and platelet membranes. Altered distribution of filamin A and actin and delocalization of the von Willebrand factor were also shown. Overall, this study expands our knowledge of GALE-related thrombocytopenia and emphasizes the critical role of GALE in the physiological glycosylation of key proteins involved in platelet production and function.
Genetic mutations affecting glycosylation can contribute to abnormal platelet production and function. In this context, Marín-Quílez and colleagues characterize the functions of UDP-galactose-4-epimerase (GALE), identifying 3 new GALE mutations in patients with macrothrombocytopenia, and moderate-to-severe bleeding tendencies. The authors explain their phenotypic effects on platelet production, structure, and function through elegant mechanistic studies.
Resistance training (RT) and n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation have emerged as strategies to improve muscle function in older adults. Overweight/obese postmenopausal women ...(55–70 years) were randomly allocated to one of four experimental groups, receiving placebo (olive oil) or docosahexaenoic acid (DHA)-rich n-3 PUFA supplementation alone or in combination with a supervised RT-program for 16 weeks. At baseline and at end of the trial, body composition, anthropometrical measures, blood pressure and serum glucose and lipid biomarkers were analyzed. Oral glucose tolerance tests (OGTT) and strength tests were also performed. All groups exhibit a similar moderate reduction in body weight and fat mass, but the RT-groups maintained bone mineral content, increased upper limbs lean mass, decreased lower limbs fat mass, and increased muscle strength and quality compared to untrained-groups. The RT-program also improved glucose tolerance (lowering the OGTT incremental area under the curve). The DHA-rich supplementation lowered diastolic blood pressure and circulating triglycerides and increased muscle quality in lower limbs. In conclusion, 16-week RT-program improved segmented body composition, bone mineral content, and glucose tolerance, while the DHA-rich supplement had beneficial effects on cardiovascular health markers in overweight/obese postmenopausal women. No synergistic effects were observed for DHA supplementation and RT-program combination.
The stone marten is a widely distributed mustelid in the Palaearctic region that exhibits variable habitat preferences in different parts of its range. The species is a Holocene immigrant from ...southwest Asia which, according to fossil remains, followed the expansion of the Neolithic farming cultures into Europe and possibly colonized the Iberian Peninsula during the Early Neolithic (ca. 7,000 years BP). However, the population genetic structure and historical biogeography of this generalist carnivore remains essentially unknown. In this study we have combined mitochondrial DNA (mtDNA) sequencing (621 bp) and microsatellite genotyping (23 polymorphic markers) to infer the population genetic structure of the stone marten within the Iberian Peninsula. The mtDNA data revealed low haplotype and nucleotide diversities and a lack of phylogeographic structure, most likely due to a recent colonization of the Iberian Peninsula by a few mtDNA lineages during the Early Neolithic. The microsatellite data set was analysed with a) spatial and non-spatial Bayesian individual-based clustering (IBC) approaches (STRUCTURE, TESS, BAPS and GENELAND), and b) multivariate methods discriminant analysis of principal components (DAPC) and spatial principal component analysis (sPCA). Additionally, because isolation by distance (IBD) is a common spatial genetic pattern in mobile and continuously distributed species and it may represent a challenge to the performance of the above methods, the microsatellite data set was tested for its presence. Overall, the genetic structure of the stone marten in the Iberian Peninsula was characterized by a NE-SW spatial pattern of IBD, and this may explain the observed disagreement between clustering solutions obtained by the different IBC methods. However, there was significant indication for contemporary genetic structuring, albeit weak, into at least three different subpopulations. The detected subdivision could be attributed to the influence of the rivers Ebro, Tagus and Guadiana, suggesting that main watercourses in the Iberian Peninsula may act as semi-permeable barriers to gene flow in stone martens. To our knowledge, this is the first phylogeographic and population genetic study of the species at a broad regional scale. We also wanted to make the case for the importance and benefits of using and comparing multiple different clustering and multivariate methods in spatial genetic analyses of mobile and continuously distributed species.
A patient who underwent previous implantation of a mitral valve replacement with a Björk-Shiley Delrin (BSD) mitral valve prosthesis during infancy was admitted to our institution 43 years later ...after an episode of syncope and cardiac arrest. Under extreme hemodynamic instability, a mitral valve prosthetic dysfunction causing massive mitral regurgitation was identified. The patient underwent an emergent cardiac operation, and a complete disc fracture with partial disc migration was found. Exceptional cases of mechanical prosthetic heart valve fracture exist. We report the first case of complete transversal disc rupture of a BSD mitral valve prosthesis after the longest period of implantation ever reported in that position.
We analysed the effects of the Nike ZoomX Vaporfly (VPF) on long-interval training performance, kinematic parameters, running power and fatigue compared to a traditional running shoe. Twelve ...well-trained men (mean ± SD: 32.91 ± 7.50 years; 69.29 ± 7.55 kg and 172.73 ± 5.97 cm) performed two long-interval training sessions (5 × 1000 m with 90s recovery period) 7 days apart, with the VPF shoe or a traditional running shoe (CON) in random order. The countermovement jump (CMJ) height was measured before and after the training sessions and heart rate, spatiotemporal parameters, running power and leg stiffness was measured during training sessions. Running-related pain was assessed prior and post-24 h of each training session. Long-interval training performance improved 2.4% using the VPF shoe compared to CON (
= 0.009; ES = 0.482). Step length, contact time and leg stiffness were higher (
< 0.05; ES = 0.51, ES = 0.677, ES = 0.356) while flight time was lower (
< 0.001; ES = 0.756) when using VPF. Running power decreased in a similar way in both conditions throughout the training session. Vertical power was significantly higher in the VPF condition (
= 0.023, ES = 0.388). CMJ height decreased in both conditions after training (4.7 vs. 7.2%, for the VPF and control, respectively,
< 0.001; ES = 0.573). Finally, the perceived muscle pain was influenced by the shoe model condition (chi-square 5.042,
= 0.025). VPF shoes improved the long-interval training performance with similar running power, heart rate and neuromuscular fatigue, and reduced subjective perceived muscle pain compared to regular training shoes.
VPF shoe may improve long-interval training performance in trained runners with the same running power and heart rate.Lower subjective perceived muscle pain is found with VPF compared to the regular training shoes.This type of footwear may be used in high-intensity training sessions aiming to increase the training volume at higher intensities with lower associated fatigue.
A patient was submitted to mitral valve replacement and tricuspid ring annuloplasty. During immediate postoperative course, signs of inferior myocardial ischemia appeared. Acute entrapment of the ...right coronary artery due to tricuspid ring sutures was confirmed by coronary angiography. The patient was reoperated and a right coronary bypass graft was successfully performed. Tricuspid procedures have shown to be effective and secure with a low rate of complication. Few cases of right coronary artery occlusion have been described and the majority not treated. Exceptional cases of right coronary occlusion related to tricuspid ring annuloplasty have been reported with a favorable outcome, as the case described herein.
Interval training (IT) is influenced by several variables and its design. However, there is no consensus about the acute effects of this type of training on running kinematics and gait patterns due ...to the variety of session designs.
The aim of this systematic review was to determine the acute effects of IT on gait patterns and running kinematics in endurance runners depending on the characteristics of the training sessions.
A systematic search on four databases (Pubmed, WOS, Medline, and Scopus) was conducted on February 22, 2022. After analyzing 655 articles, studies were included if they met the inclusion criteria developed according to the PICO model. Nine studies were finally included.
Only two of these studies measured kinematics changes during IT bouts while seven measured pre-post changes of these parameters. The quality scores of the included studies in the review averaged 5.44 (good quality) points using the modified PEDro scale. The observed changes in running kinematics during IT sessions were an increase in stride frequency, contact time and vertical displacement of center of mass.
Regarding the type of IT, anaerobic and short aerobic interval sessions (200–1000 m) should include long recovery periods (2–3 min) to avoid the increase of stride frequency, contact time and vertical oscillation of the center of mass as a results of muscle fatigue. For long aerobic interval sessions (>1000 m), a short recovery (1–2 min) between bouts do not induce a high level of muscle fatigue nor modifications in gait patterns. Coaches and athletes must consider the relative intensity and recovery periods of IT, and the type of IT, to prevent excessive fatigue which can negatively affect running kinematics.
•Longer rest periods (∼2 min) during IT protocols help support running kinematics.•In long aerobic IT, recovery < 1 min ensures that running kinematics remains unchanged.•In anaerobic IT, a recovery time ∼4 min helps to tolerate neuromuscular fatigue.•Cardiovascular fatigue appears before neuromuscular fatigue.•Monitoring of cardiometabolic parameters is recommended to improve fatigue control.
Type 2 diabetes mellitus (T2DM) is an emerging risk factor for cognitive impairment. Whether this impairment is a direct effect of this metabolic disorder on brain function, a consequence of vascular ...disease, or both, remains unknown. Structural and functional neuroimaging studies in patients with T2DM could help to elucidate this question.
We designed a cross-sectional study comparing 25 T2DM patients with 25 age- and gender-matched healthy control participants. Clinical information, APOE genotype, lipid and glucose analysis, structural cerebral magnetic resonance imaging including voxel-based morphometry, and F-18 fluorodeoxyglucose positron emission tomography were obtained in all subjects.
Gray matter densities and metabolic differences between groups were analyzed using statistical parametric mapping. In addition to comparing the neuroimaging profiles of both groups, we correlated neuroimaging findings with HbA1c levels, duration of T2DM, and insulin resistance measurement (HOMA-IR) in the diabetic patients group.
Patients with T2DM presented reduced gray matter densities and reduced cerebral glucose metabolism in several fronto-temporal brain regions after controlling for various vascular risk factors. Furthermore, within the T2DM group, longer disease duration, and higher HbA1c levels and HOMA-IR were associated with lower gray matter density and reduced cerebral glucose metabolism in fronto-temporal regions.
In agreement with previous reports, our findings indicate that T2DM leads to structural and metabolic abnormalities in fronto-temporal areas. Furthermore, they suggest that these abnormalities are not entirely explained by the role of T2DM as a cardiovascular risk factor.
The primary goal of the present research was to determine the order of swimmers on a mixed relay team that would ensure the best performance in the Fédération Internationale de Natation (FINA) World ...Championships held in Kazan (Russia, 2015), Budapest (Hungary, 2017), and Gwangju (South Korea, 2019). The data were obtained from database websites for the 4 × 100 m freestyle and 4 × 100 m medley official results, including 660 records from 188 entries of finals and 472 preliminary events. The results showed that the fastest swimmers (according to their best season times) were located primarily in the first or second positions of the freestyle relay. The most successful gender strategy for the 4 × 100 m freestyle (57 out of 82 observations) and for the 4 × 100 m medley (29 out of 83) relays was the order male-male-female-female, although no statistical differences were found (
= 0.79) for the medley relays. In the 4 × 100 m freestyle, the second (
= 0.002;
= 1.62) and third (
=0.003;
= 1.41) relay legs had a statistical effect on the total relay time, whereas in the 4 × 100 m medley, all four relay legs had a statistical effect (
< 0.001) on the final performance, the weight of the four strokes being different in heats with respect to the final round. Also, a later position of the first female swimmer or the consecutive position of two female swimmers in the team order significantly affected the relay performance in specific events. Mixed relay events appeared to present specific strategies in comparison to traditional male- or female-only relay lineups.
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