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1.
Artículo en Inglés | MEDLINE | ID: mdl-38849301

RESUMEN

CONTEXT: The CERT1 (Cardiovascular Event Risk Test) score derived from plasma ceramides has been applied clinically for cardiovascular risk assessment. OBJECTIVE: To study whether plasma ceramides predict risk of mortality in patients with type 2 diabetes. DESIGN, SETTING AND PARTICIPANTS: A prospective study which included 1903 outpatients with type 2 diabetes in a regional hospital and a primary care facility in Singapore. EXPOSURE AND OUTCOME: Plasma ceramides (d18:1/16:0, d18:1/18:0, d18:1/24:0, d18:1/24:1) were measured by mass spectrometry and CERT1 score was calculated accordingly. Main outcomes were all-cause and cause-specific mortality. RESULTS: 252 death events were identified during median of 9.3 years of follow-up. Compared to those with low score (≤ 2), participants with a high CERT1 score (≥ 7) had 1.86 (95% CI 1.30-3.65) fold increased risk for all-cause death after adjustment for cardio-renal risk factors including eGFR and albuminuria. As continuous variable, one- unit increment in CERT1 was associated with 8% increased risk for all-cause death (adjusted HR 1.08 [1.04-1.13]). Adding CERT1 onto RECODe (Risk Equations for Complications Of type 2 Diabetes) mortality risk engine significantly improved prediction of 10- year risk of all-cause death (AUC 0.810 to 0.823, delta 0.013 [0.005-0.022]). The association between CERT1 and non-cardiovascular death remained significant (adjusted HR 2.12 [1.32-3.42]), whereas its association with cardiovascular death became non-significant after adjustment for kidney measurements (adjusted HR 1.41 [0.78-2.56]). CONCLUSION: CERT1 score predicts mortality risk independent of clinical cardio-renal risk factors. Further studies are warranted to elucidate the mechanistic linkage between ceramide and mortality, especially non-cardiovascular mortality.

2.
Contact (Thousand Oaks) ; 7: 25152564241239443, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38515862

RESUMEN

Phosphatidylinositol 4-monophosphate (PtdIns(4)P) is one of the key membrane components which mark the membrane contact sites. In the mammalian Golgi complex, PtdIns(4)P is produced at various subregions via specific mechanisms for each site. Particularly, PtdIns(4)P pools generated at the distal Golgi regions are pivotal for the determination of membrane contacts between the endoplasmic reticulum (ER) and Golgi, at which inter-organelle lipid transport takes place. In this short review, we will focus on C10orf76 (or ARMH3), which we propose to rename as DGARM after a distal Golgi armadillo repeat protein, for its function in generating a PtdIns(4)P pool crucial for ER-to-distal Golgi ceramide transport. We further discuss from the viewpoint of the evolutionary conservation of DGARM.

3.
Eur Heart J Open ; 4(1): oeae001, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38292914

RESUMEN

Aims: Low-density lipoprotein cholesterol (LDL-C) is the best documented cardiovascular risk predictor and at the same time serves as a target for lipid-lowering therapy. However, the power of LDL-C to predict risk is biased by advanced age, comorbidities, and medical treatment, all known to impact cholesterol levels. Consequently, such biased patient cohorts often feature a U-shaped or inverse association between LDL-C and cardiovascular or overall mortality. It is not clear whether these constraints for risk prediction may likewise apply to other lipid risk markers in particular to ceramides and phosphatidylcholines. Methods and results: In this observational cohort study, we recorded cardiovascular mortality in 1195 patients over a period of up to 16 years, comprising a total of 12 262 patient-years. The median age of patients at baseline was 67 years. All participants were either consecutively referred to elective coronary angiography or diagnosed with peripheral artery disease, indicating a high cardiovascular risk. At baseline, 51% of the patients were under statin therapy. We found a U-shaped association between LDL-C and cardiovascular mortality with a trough level of around 150 mg/dL of LDL-C. Cox regression analyses revealed that LDL-C and other cholesterol species failed to predict cardiovascular risk. In contrast, no U-shaped but linear association was found for ceramide- and phosphatidylcholine-containing markers and these markers were able to significantly predict the cardiovascular risk even after multivariate adjustment. Conclusion: We thus suggest that ceramides- and phosphatidylcholine-based predictors rather than LDL-C may be used for a more accurate cardiovascular risk prediction in high-risk patients.

4.
J Orthop Sports Phys Ther ; 54(2): 1-11, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37970804

RESUMEN

OBJECTIVE: To identify barriers and facilitators for using intervention reporting guidelines (CERT and TIDieR) from authors of randomized controlled trials in sports and exercise medicine journals. DESIGN: Mixed-methods cross-sectional online survey. METHODS: We recruited authors of randomized controlled trials published from June 2, 2018, to June 2, 2022, in the 10 leading sports and exercise medicine journals. We invited authors of eligible trials to complete an online survey that included multiple-choice and Likert-scale questions, as well as open-ended free-text questions on the barriers and facilitators to using intervention reporting guidelines. We used descriptive analysis to summarize the quantitative data and a hybrid deductive-inductive thematic analysis to identify barriers and facilitators from the qualitative data. We conducted a subgroup analysis to explore differences in barriers and facilitators between early-mid career researchers and senior researchers. RESULTS: Eighty-four participants from 21 countries completed the survey (44 early-mid-career researchers, 40 senior researchers). We identified 8 themes relating to using intervention reporting guidelines. Themes classified as barriers related to publication constraints (word count limits), low awareness of intervention reporting guidelines, unclear benefits of the guidelines, and the increased burden imposed upon the researcher. Themes classified as facilitators related to journal requirements for guidelines use, the desire to accurately describe interventions, recommendations from other researchers, and reporting guideline use indicating "quality" of work. CONCLUSION: Barriers to using intervention reporting guidelines are largely modifiable and could be addressed by journals mandating their use, and educational initiatives. J Orthop Sports Phys Ther 2024;54(2):1-11. Epub 16 November 2023. doi:10.2519/jospt.2023.12110.


Asunto(s)
Proyectos de Investigación , Deportes , Humanos , Estudios Transversales , Ejercicio Físico , Encuestas y Cuestionarios
5.
Arch Biochem Biophys ; 752: 109871, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38110110

RESUMEN

Ether phospholipids are synthesized by a series of enzymes localized in peroxisomes, the endoplasmic reticulum (ER), and the Golgi apparatus. During this process, the lipid intermediate alkylacylglycerol (AAG) synthesized in the ER is transferred from the site of its synthesis to the Golgi apparatus. In this study, we determined whether ceramide transport protein (CERT) is a candidate for AAG transfer. A lipid transfer assay revealed that CERT can mediate AAG transfer between phospholipid liposomes. AAG transport activity was markedly inhibited by the CERT inhibitor HPA-12 and reduced when the lipid transport domain of CERT was deleted. Suppression of CERT in HEK293 cells resulted in increased levels of plasmanyl-PC, which is synthesized by the ER-residing choline/ethanolamine phosphotransferase 1 (CEPT1). The mRNA levels and enzymatic activity of plasmanyl-PC synthesizing enzymes were not increased in CERT-deficient cells, indicating that the increase in plasmanyl-PC results from AAG accumulation in the ER. Re-introduction of CERT into CERT-deficient cells caused a decrease in plasmanyl-PC. Taken together, our findings suggest for the first time that CERT is involved in the transfer of AAG from the ER to the Golgi apparatus and plays a role in the biosynthesis of ether phospholipids.


Asunto(s)
Proteínas Portadoras , Ceramidas , Humanos , Transporte Biológico , Proteínas Portadoras/metabolismo , Ceramidas/metabolismo , Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Células HEK293 , Éteres Fosfolípidos/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo
6.
J Clin Med ; 12(24)2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38137595

RESUMEN

Ceramides and other sphingolipids are implicated in vascular dysfunction and inflammation. They have been suggested as potential biomarkers for hypertension. However, their specific association with hypertension prevalence and onset requires further investigation. This study aimed to identify specific ceramide and phosphatidylcholine species associated with hypertension prevalence and onset. The 2002 FINRISK (Finnish non-communicable risk factor survey) study investigated the association between coronary event risk scores (CERT1 and CERT2) and hypertension using prevalent and new-onset hypertension groups, both consisting of 7722 participants, over a span of 10 years. Ceramide and phosphatidylcholine levels were measured using tandem liquid chromatography-mass spectrometry. Ceramide and phosphatidylcholine ratios, including ceramide (d18:1/18:0), ceramide (d18:1/24:1), phosphatidylcholine (16:0/16:0), and the ratio of ceramide (d18:1/18:0)/(d18:1/16:0), are consistently associated with both prevalence and new-onset hypertension. Ceramide (d18:1/24:0) was also linked to both hypertension measures. Adjusting for covariates, CERT1 and CERT2 showed no-longer-significant associations with hypertension prevalence, but only CERT2 predicted new-onset hypertension. Plasma ceramides and phosphatidylcholines are crucial biomarkers for hypertension, with imbalances potentially contributing to its development. Further research is needed to understand the underlying mechanisms by which ceramides will contribute to the development of hypertension.

7.
J Clin Med ; 12(19)2023 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-37834795

RESUMEN

(1) Background: Ceramides are a new kind of lipid biomarker and have already been demonstrated to be valuable risk predictors in coronary patients. Patients with peripheral artery disease (PAD) are a population with a worse prognosis and higher mortality risk compared to coronary artery disease (CAD) patients. However, the value of ceramides for risk prediction in PAD patients is still vague, as addressed in the present study. (2)Methods: This observational study included 379 PAD patients. The primary endpoint was all-cause mortality at 10 years of follow-up. A set of ceramides was measured by LC-MS/MS and combined according to the Coronary Event Risk Test (CERT) score, which categorizes patients into one of four risk groups (low risk, moderate risk, high risk, very high risk). (3) Results: Kaplan-Meier survival curves revealed that the overall survival of patients decreased with the increasing risk predicted by the four CERT categories, advancing from low risk to very high risk. Cox regression analysis demonstrated that each one-category increase resulted in a 35% rise in overall mortality risk (HR = 1.35 [1.16-1.58]). Multivariable adjustment, including, among others, age, LDL-cholesterol, type 2 diabetes, and statin treatment before the baseline, did not abrogate this significant association (HR = 1.22 [1.04-1.43]). Moreover, we found that the beneficial effect of statin treatment is significantly stronger in patients with a higher risk, according to CERT. (4) Conclusions: We conclude that the ceramide-based risk score CERT is a strong predictor of the 10-year mortality risk in patients with PAD.

8.
Int J Mol Sci ; 24(15)2023 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-37569827

RESUMEN

Ceramide risk score (CERT1, ceramide test 1), based on specific ceramides (Cers) and their corresponding ratios in the plasma, has been reported as a promising biochemical marker for primary and secondary prediction of cardiovascular disease (CVD) risk in different populations of patients. Thus far, limited attention has been paid to metabolic syndrome, a condition considered at high CVD risk. The aim of the present study was to evaluate CERT1 in a group of obese subjects without (OB-MetS-) and with (OB-MetS+) metabolic syndrome (according to the International Diabetes Federation (IDF) diagnostic criteria), compared to an age- and sex-matched normal-weight (NW) group. In all participants, plasma levels of Cer 16:0, Cer 18:0, Cer 24:1, and Cer 24:0 were measured, and the corresponding ratios Cer 16:0/24:0, Cer 18:0/24:0, and Cer 24:1/24:0 were calculated together with CERT1. Subjects with obesity showed higher CERT1 values than the NW group (p < 0.05), with no difference between OB-MetS- and OB-MetS+ groups. Waist circumference (WC), homeostatic model assessment of insulin-resistance (HOMA-IR) (surrogates of IDF diagnostic criteria for metabolic syndrome), and C reactive protein (CRP) (a marker of inflammation) were predictors of CERT1 (p < 0.05), with the contribution of the other IDF criteria such as arterial hypertension and dyslipidemia being negligible. Adjustment for WC resulted in a loss of the difference in CERT1 between OB-MetS- and NW subjects, with the combination of WC and HOMA-IR or CRP as covariates being necessary to yield the same effect for the difference in CERT1 between OB-MetS+ and NW subjects. Importantly, an association was found between CERT1 and vascular age (VA) (p < 0.05). Proportions of NW, OB-MetS- and OB-MetS+ subjects appeared to be distributed according to the CERT1-based risk groups (i.e., low, moderate, increased, and high risk; p < 0.05), with some OB-MetS- subjects included in the increased/high-risk group and some OB-MetS+ in the low/moderate-risk one. In conclusion, the clinical diagnosis of metabolic syndrome seems to be inaccurate to assess CVD risk in the obese population; however, further studies are needed before considering CERT1 as an additional or substitutive biochemical marker in clinical practice.

9.
COPD ; 20(1): 216-223, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37439578

RESUMEN

In Japan, exacerbations are underreported compared with other countries, possibly due in part to a failure to recognize them. This study aimed to create a simple chronic obstructive pulmonary disease (COPD) Exacerbation Recognition Tool (CERT-J) specifically for Japanese patients. Patients ≥40 years with confirmed COPD or asthma-COPD overlap were included. Focus groups were held to identify words and phrases used by patients to describe symptoms associated with an exacerbation, resulting in candidate items being identified. Following cognitive debriefing, the items were refined based on item frequency, level of endorsement and effect of demographic factors. Exploratory factor analysis (EFA) was then performed to inform an expert panel's choice of items to form the new tool. A total of 41 patients were included in the focus groups and nine patients performed the cognitive debrief. Following this, the expert panel identified 26 items for testing in a further 100 patients (mean age 72 years, forced expiratory volume in 1 s 54.8% predicted and 1.8 exacerbations in the preceding 12 months). Eleven items were associated with breathlessness or activity limitation and seven of these were the most frequently endorsed. EFA identified four factors, with one (breathlessness) being dominant. The expert panel recommended that the CERT-J should include six items: breathlessness and activity limitation (3 items), cough (1 item) and phlegm (2 items). The final CERT-J should benefit patients with COPD by providing them with an increased understanding and recognition of exacerbations.Clinical Trial Registration: GSK K.K (jRCT1080224526).


Asunto(s)
Médicos , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Humanos , Progresión de la Enfermedad , Disnea/diagnóstico , Disnea/etiología , Volumen Espiratorio Forzado , Japón , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Adulto , Persona de Mediana Edad
10.
Int Cybersecur Law Rev ; 4(1): 39-60, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36798529

RESUMEN

Computer Security Incident Response Teams (CSIRTs) or Computer Emergency Response Teams (CERTs) are an integral part of incident handling capabilities and are increasingly demanded by organizations such as critical infrastructures. They can hold many different skills and are of great interest to organizations in terms of cyber security and, more concretely, cyber incident management. This contribution seeks to analyze the extent to which their activity is regulated under Swiss law, considering that private CSIRTs are not regulated in the same way as governmental and national CSIRTs such as the Computer Emergency Response Team of the Swiss government and official national CERT of Switzerland (GovCERT).

11.
Int J Mol Sci ; 23(23)2022 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-36499025

RESUMEN

The obligate intracellular bacterium Chlamydia trachomatis is the major causative agent of bacterial sexually transmitted diseases worldwide. In infected cells, the ceramide transport protein (CERT) is recruited to inclusions, where C. trachomatis replicates using host-synthesized ceramide. The ceramide is converted to sphingomyelin (SM) by a chlamydial infection-dependent SM synthesis (cidSM-synthesis) pathway, which occurs even in the absence of the SM synthases (SMS)-1 and -2 of host cells. The ceramide mimetic compound (1R,3S)-HPA-12 and the nonmimetic compound E16A, both of which are potent inhibitors of CERT, repressed the proliferation of C. trachomatis in HeLa cells. Unexpectedly, (1R,3R)-HPA-12, a ceramide mimetic compound that lacks CERT inhibitory activity, also exhibited potent anti-chlamydial activity. Using endogenous SMS-knockout mutant HeLa cells, we revealed that (1R,3R)-HPA-12 mildly inhibited cidSM-synthesis. In addition, LC-MS analysis revealed that (1R,3R)-HPA-12 is converted to a phosphocholine-conjugated metabolite in an infection-dependent manner. Imaging analysis with a fluorescent analog of ceramide suggested that cidSM-synthesis occurs in the bacterial bodies and/or inclusions. Collectively, these results suggested that (1R,3R)-HPA-12 exerts its anti-chlamydia activity not only as an inhibitor of cidSM-synthesis, but also via putative toxic effects of its phosphocholine adduct, which is most likely produced by the cidSM-synthesis route.


Asunto(s)
Ceramidas , Esfingomielinas , Humanos , Esfingomielinas/metabolismo , Ceramidas/farmacología , Ceramidas/metabolismo , Células HeLa , Fosforilcolina/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Chlamydia trachomatis/metabolismo
12.
Int J Mol Sci ; 23(15)2022 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-35955719

RESUMEN

Ceramide transport protein (CERT) mediates ceramide transfer from the endoplasmic reticulum to the Golgi for sphingomyelin (SM) biosynthesis. CERT is inactivated by multiple phosphorylation at the serine-repeat motif (SRM), and mutations that impair the SRM phosphorylation are associated with a group of inherited intellectual disorders in humans. It has been suggested that the N-terminal phosphatidylinositol 4-monophosphate [PtdIns(4)P] binding domain and the C-terminal ceramide-transfer domain of CERT physically interfere with each other in the SRM phosphorylated state, thereby repressing the function of CERT; however, it remains unclear which regions in CERT are involved in the SRM phosphorylation-dependent repression of CERT. Here, we identified a previously uncharacterized cluster of lysine/arginine residues that were predicted to be located on the outer surface of a probable coiled-coil fold in CERT. Substitutions of the basic amino acids in the cluster with alanine released the SRM-dependent repression of CERT activities, i.e., the synthesis of SM, PtdIns(4)P-binding, vesicle-associated membrane protein-associated protein (VAP) binding, ceramide-transfer activity, and localization to the Golgi, although the effect on SM synthesis activity was only partially compromised by the alanine substitutions, which moderately destabilized the trimeric status of CERT. These results suggest that the basic amino acid cluster in the coiled-coil region is involved in the regulation of CERT function.


Asunto(s)
Proteínas Portadoras , Ceramidas , Alanina/metabolismo , Aminoácidos Básicos/metabolismo , Transporte Biológico/fisiología , Proteínas Portadoras/metabolismo , Ceramidas/metabolismo , Aparato de Golgi/metabolismo , Humanos , Fosfatidilinositoles/metabolismo , Fosforilación , Proteínas Serina-Treonina Quinasas , Serina/metabolismo
13.
J Extracell Vesicles ; 11(6): e12233, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35642450

RESUMEN

The formation of extracellular vesicles (EVs) is induced by the sphingolipid ceramide. How this pathway is regulated is not entirely understood. Here, we report that the ceramide transport protein (CERT) mediates a non-vesicular transport of ceramide between the endoplasmic reticulum (ER) and the multivesicular endosome at contact sites. The process depends on the interaction of CERT's PH domain with PI4P generated by PI4KIIα at endosomes. Furthermore, a complex is formed between the START domain of CERT, which carries ceramide, and the Tsg101 protein, which is part of the endosomal sorting complex required for transport (ESCRT-I). Inhibition of ceramide biosynthesis reduces CERT-Tsg101 complex formation. Overexpression of CERT increases EV secretion while its inhibition reduces EV formation and the concentration of ceramides and sphingomyelins in EVs. In conclusion, we discovered a function of CERT in regulating the sphingolipid composition and biogenesis of EVs, which links ceramide to the ESCRT-dependent pathway.


Asunto(s)
Vesículas Extracelulares , Esfingolípidos , Proteínas Portadoras , Ceramidas , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Vesículas Extracelulares/metabolismo , Proteínas Serina-Treonina Quinasas
14.
J Clin Lipidol ; 16(3): 272-276, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35219648

RESUMEN

Accumulating evidence over the last decade suggests the promising role of ceramides as potential mediators of coronary artery disease (CAD) or prognostic biomarkers of its clinical course. This meta-analysis (CRD42021241058) aimed to assess the prognostic value of a ceramide- and phosphatidylcholine-based risk score, Coronary Event Risk Test 2 (CERT2) score, for the prediction of major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction or stroke) in 26,896 individuals with established CAD. Patients with CERT2=0-3 were used as a reference group. Pooled risk ratio (RR) of MACE among patients with CERT2=4-6 was equal to 1.35 (95% confidence intervals, CI: 1.11-1.64). Patients with CERT2=7-8 had an 81% increased risk of MACE (RR=1.81, CI: 1.40-2.34), while those with CERT2=9-12 had a 165% increased risk of MACE (RR=2.65, CI: 1.85-3.80). Subgroup analysis in patients with chronic coronary syndrome yielded an adjusted hazard ratio for MACE equal to 1.20 (CI: 1.09-1.32) per one standard deviation increase of CERT2 score. A summary c-statistic of the score combined with classical risk assessment model was found equal to 0.68 (95% CI: 0.58 to 0.77; approximate 95% prediction interval 0.38 to 0.88). Therefore, CERT2 score seems to emerge as a robust predictor of MACE. However, additional research is warranted to establish the cost-effectiveness of CERT2 score calculation for the determination of residual risk in patients with CAD.


Asunto(s)
Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Ceramidas , Humanos , Fosfolípidos , Pronóstico , Medición de Riesgo , Factores de Riesgo
15.
Int J Mol Sci ; 23(4)2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-35216212

RESUMEN

Lipid transfer proteins (LTPs) are recognized as key players in the inter-organelle trafficking of lipids and are rapidly gaining attention as a novel molecular target for medicinal products. In mammalian cells, ceramide is newly synthesized in the endoplasmic reticulum (ER) and converted to sphingomyelin in the trans-Golgi regions. The ceramide transport protein CERT, a typical LTP, mediates the ER-to-Golgi transport of ceramide at an ER-distal Golgi membrane contact zone. About 20 years ago, a potent inhibitor of CERT, named (1R,3S)-HPA-12, was found by coincidence among ceramide analogs. Since then, various ceramide-resembling compounds have been found to act as CERT inhibitors. Nevertheless, the inevitable issue remains that natural ligand-mimetic compounds might directly bind both to the desired target and to various undesired targets that share the same natural ligand. To resolve this issue, a ceramide-unrelated compound named E16A, or (1S,2R)-HPCB-5, that potently inhibits the function of CERT has recently been developed, employing a series of in silico docking simulations, efficient chemical synthesis, quantitative affinity analysis, protein-ligand co-crystallography, and various in vivo assays. (1R,3S)-HPA-12 and E16A together provide a robust tool to discriminate on-target effects on CERT from off-target effects. This short review article will describe the history of the development of (1R,3S)-HPA-12 and E16A, summarize other CERT inhibitors, and discuss their possible applications.


Asunto(s)
Transporte Biológico/fisiología , Ceramidas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Humanos , Ligandos
16.
J Orthop Sports Phys Ther ; 52(3): 130-141, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34546816

RESUMEN

OBJECTIVE: To review the quality of reporting and identify the content of exercise interventions prescribed for hamstring strain injury (HSI) rehabilitation in the scientific literature from 2010 to 2020. DESIGN: Scoping review. LITERATURE SEARCH: We searched the bibliometric databases Web of Science, CINAHL, SPORTDiscus, Scopus, Cochrane Library, MEDLINE, and Embase. STUDY SELECTION CRITERIA: Original research articles (randomized controlled trials and cohort studies) published from 2010 to 2020 that described an exercise rehabilitation intervention for participants with acute HSIs were included. Injuries must have been confirmed within 7 days of occurrence via clinical assessment and/or diagnostic imaging. DATA SYNTHESIS: The quality of reporting, in terms of completeness of exercise intervention description, was evaluated using the Consensus on Exercise Reporting Template (CERT), and the content of interventions was categorized into exercise types. RESULTS: Fourteen studies were included; exercise intervention quality of reporting was moderate in 3 studies and low in 11 studies. Using the 19-item CERT, an average of 8.8 items (range, 4-14) were reported across all studies. Two studies reported sufficient exercise content and progression information to allow replication. Exercises categorized as hamstring flexibility, hamstring strength, running related, and non-hamstring specific were prescribed in 13, 11, 10, and 10 studies, respectively. Half of the included studies incorporated all 4 exercise types in their exercise interventions. CONCLUSION: There is a wide variety of exercise interventions applied in published research that has addressed HSI rehabilitation. Researchers must improve reporting quality to support other professionals in replicating exercise interventions and help practitioners to effectively implement research in practice. J Orthop Sports Phys Ther 2022;52(3):130-141. Epub 21 Sep 2021. doi:10.2519/jospt.2022.10641.


Asunto(s)
Músculos Isquiosurales , Traumatismos de la Pierna , Traumatismos de los Tejidos Blandos , Ejercicio Físico , Terapia por Ejercicio , Músculos Isquiosurales/lesiones , Humanos
17.
Curr Diabetes Rev ; 18(4): e250821195838, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34433402

RESUMEN

BACKGROUND: Exercise is strongly recommended for the management of type 2 diabetes mellitus (T2DM). However, incomplete intervention reporting in clinical trials limits the replication of exercise protocols. As previously demonstrated by us for exercise and hypertension, the reporting quality might also be insufficient in studies with respect to T2DM and exercise. OBJECTIVE: The aim of the study was to assess the completeness of exercise intervention reporting in randomized controlled trials (RCTs) for T2DM. METHODS: Two independent reviewers applied the Consensus on Exercise Reporting Template (CERT) and the template for intervention description and replication (TIDieR) to 23 exercise trials obtained from the most recent and frequently cited meta-analysis in current guidelines. The completeness of reporting was evaluated, focusing on the F.I.T.T. components (frequency, intensity, time, type). Interrater agreement and associations with publication year and journal impact factor were examined. RESULTS: Mean CERT score was 11/19 (range 5-17), and 8/12 (range 4-12) for TIDieR. F.I.T.T. components were almost completely described, whereas overall completeness of exercise reporting was 60% and 68% (CERT and TIDieR). Replication of each exercise of the respective program was not possible in 52% of interventions. The majority of items had shown excellent agreement. No associations with publication year or impact factor were found. CONCLUSION: Exercise interventions were not found to be sufficiently reported in RCTs that currently guide clinical practice in T2DM. Replication in further studies or clinical practice is limited due to poor exercise description. We suggest the use of more specific CERT for reporting results of exercise interventions. Further refinement for internal diseases is needed to better describe exercise interventions.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipertensión , Consenso , Diabetes Mellitus Tipo 2/terapia , Ejercicio Físico , Terapia por Ejercicio/métodos , Humanos
18.
Artículo en Inglés | MEDLINE | ID: mdl-37008559

RESUMEN

The mechanisms by which cytoplasmic cargoes such as RNAs are incorporated into extracellular vesicles (EVs) are poorly understood. In a recent article published in Developmental Cell, we describe a novel function of endoplasmic reticulum membrane contact sites (ER MCS) in regulating biogenesis of RNA-containing EVs (Barman et al., 2022). We identified the ER MCS tether protein VAP-A and the ceramide transporter CERT as key drivers of this process. VAP-A depletion and overexpression produced corresponding changes in the overall number and RNA content of secreted EVs. Further sub-fractionation of small EVs from VAP-A depleted cells revealed a distinct loss in a specific subset of dense, RNA-loaded small EVs that are critical for the transfer of miR-100 to recipient cells. Cell imaging data confirmed the loss of RNA and RNA binding proteins (RBPs) in VAP-A-knockdown multivesicular bodies. Lipid analysis of VAP-A-knockdown EVs revealed decreases in ceramides, which are known to affect EV biogenesis. Depletion of the ceramide transfer protein CERT, which interacts with its binding partner VAP-A at ER MCS, leads to similar defects in EV number and RNA content as VAP-A-knockdown. These data suggest a model for ER MCS as platforms for biogenesis of a key EV population via ceramide transfer and RNA loading.

19.
NMR Biomed ; 35(1): e4610, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34636458

RESUMEN

Chemical exchange saturation transfer (CEST) methods measure the effect of magnetization exchange between solutes and water. While CEST methods are often implemented using a train of off-resonant shaped RF pulses, they are typically analyzed as if the irradiation were continuous. This approximation does not account for exchange of rotated magnetization, unique to pulsed irradiation and exploited by chemical exchange rotation transfer methods. In this work, we derive and test an analytic solution for the steady-state water signal under pulsed irradiation by extending a previous work to include the effects of pulse shape. The solution is largely accurate at all offsets, but this accuracy diminishes at higher exchange rates and when applying pulse shapes with large root-mean-squared to mean ratios (such as multi-lobe sinc pulses).


Asunto(s)
Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Análisis Numérico Asistido por Computador , Estudios de Validación como Asunto
20.
J Orthop Sports Phys Ther ; 52(2): 100-112, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34784243

RESUMEN

OBJECTIVE: To (1) describe which strength training exercise descriptors are reported in anterior cruciate ligament reconstruction (ACLR) rehabilitation research, and (2) compare the current standards of reporting ACLR strength training exercise descriptors to international best-practice strength training guidelines. DESIGN: Scoping review. LITERATURE SEARCH: We searched the MEDLINE, PsycINFO, CINAHL, SPORTDiscus, Academic Search, ERIC, Health Source: Nursing, Health Source: Consumer, MasterFILE, and Africa-Wide Information databases. STUDY SELECTION CRITERIA: We included level I to IV studies of ACLR rehabilitation programs with 1 or more reported strength training exercise descriptors. We used a predefined list of 19 exercise descriptors, based on the American College of Sports Medicine (ACSM) exercise recommendations, the Consensus on Exercise Reporting Template (CERT), and the Toigo and Boutellier exercise descriptor framework. DATA SYNTHESIS: Completeness and the standard of reporting exercise descriptors in ACLR rehabilitation programs were assessed by means of international best-practice strength training standards. RESULTS: We extracted data on 117 exercises from 41 studies. A median of 7 of the 19 possible exercise descriptors were reported (range, 3-16). Reporting of specific exercise descriptors varied across studies, from 95% (name of the strength training exercise) to 5% (exercise aim, exercise order). On average, 46%, 35%, and 43% of the exercise descriptors included in the ACSM, CERT, and Toigo and Boutellier guidelines were reported, respectively. CONCLUSION: Key exercise descriptors for muscle strength gains are not reported in studies on ACLR rehabilitation. Only the exercise name, number of exercises, frequency, and experimental period were reported in most of the studies. J Orthop Sports Phys Ther 2022;52(2):100-112. Epub 16 Nov 2021. doi:10.2519/jospt.2022.10651.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Entrenamiento de Fuerza , Lesiones del Ligamento Cruzado Anterior/rehabilitación , Lesiones del Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior/rehabilitación , Terapia por Ejercicio , Humanos , Fuerza Muscular/fisiología
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