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Background: Stretching improves range of motion and changes the viscoelastic properties of muscle-tendon units. We hypothesized that a regular stretching program would reduce the functional consequences of pain for employees working in echocardiographic, ultrasound, and interventional laboratories. This exploratory, proof-of-concept study was meant to inform expectations for future randomized, controlled studies. Methods: In this unblinded, nonrandomized, observational study, we enrolled 196 health care professionals working in the interventional and echocardiographic laboratories in the departments of cardiology and radiology at Mayo Clinic and Mayo Clinic Health System to perform 15-minute neck, upper extremity, low back, and lower extremity stretches for 1 year. The functional consequences of pain were self-reported by using the Disability of Arm, Shoulder, and Hand; Neck Disability Index; and Roland-Morris Questionnaire, which was administered at baseline and at 1 year to measure response to stretching. Monitoring with an assessment plan for injuries was undertaken. Employees who were pregnant, unable to do exercises, or under active orthopedic treatment, were excluded. Results: Of the 196 enrolled, 68 (35%) provided complete data at both baseline and follow-up. The majority of participants were over 40 years (n = 51; 72%) and female (n = 51; 72%). Participants performed stretches for 120.5 (IQR, 52-184) days over the year. The number of days of doing the stretches was well distributed across the study period with median quarters 1, 2, 3, and 4 of 32 (19-51), 32 (20-51), 31 (17-45), and 32.5 (12-47) days, respectively. The majority of participants (52.3%) stretched before, 18.9% stretched during and 28.8% stretched after work. Self-reported upper extremity disability improved in the treatment group with a significant decrease in the median Disability of Arm, Shoulder, and Hand score (5.2 to 2.6; P = .002). There was an absolute 4% decrease in the Neck Disability Index score, between baseline and 1-year follow-up (10% to 6%, P = .017). There was not a significant change in the Roland-Morris Questionnaire from baseline to follow-up (1 to 0; P = .287). No participant reported any stretch-related injuries. Conclusions: A routine stretching program may represent an attractive, low-cost, noninvasive option to reduce upper extremity musculoskeletal disability of employees working in the echocardiographic, ultrasound, and interventional laboratories. Larger randomized trials are needed to confirm the association.
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UPDATE: This article was updated on September 4, 2024 because of a previous error, which was discovered after the preliminary version of the article was posted online. In the Note listing the members of the Wrist and Elbow Research Group of Canada, the text that had read "Thomas T. Goetz, MD, FRCSC" now reads "Thomas J. Goetz, MD, FRCSC". BACKGROUND: The primary goal after open reduction and internal fixation of an established scaphoid nonunion is to achieve union. Low-intensity pulsed ultrasound (LIPUS) has been reported to increase the rate of union and to decrease the time to union for multiple fractures and nonunions in clinical and animal models. The evidence for LIPUS in the treatment of scaphoid nonunion, however, is sparse. The aim of this study was to assess whether active LIPUS (relative to sham LIPUS) accelerates the time to union following surgery for scaphoid nonunion. METHODS: Adults with a scaphoid nonunion indicated for surgery were recruited for a multicenter, prospective, double-blinded randomized controlled trial. After surgery, patients self-administered activated or sham LIPUS units beginning at their first postoperative visit. The primary outcome was the time to union on serial computed tomography (CT) scans starting 6 to 8 weeks postoperatively. Secondary outcomes included patient-reported outcome measures, range of motion, and grip strength. RESULTS: A total of 142 subjects completed the study (69 in the active LIPUS group and 73 in the sham group). The average age was 27 years, and the cohort was 88% male. There was no difference in time to union (p = 0.854; hazard ratio, 0.965; 95% confidence interval, 0.663 to 1.405). Likewise, there were no differences between the active LIPUS and sham groups with respect to any of the secondary outcomes, except for wrist flexion at baseline (p = 0.008) and at final follow-up (p = 0.043). CONCLUSIONS: Treatment with LIPUS had no effect on reducing time to union in patients who underwent surgical fixation of established scaphoid nonunions. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.
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Fracturas no Consolidadas , Hueso Escafoides , Terapia por Ultrasonido , Humanos , Hueso Escafoides/lesiones , Hueso Escafoides/cirugía , Fracturas no Consolidadas/cirugía , Fracturas no Consolidadas/terapia , Masculino , Adulto , Femenino , Terapia por Ultrasonido/métodos , Método Doble Ciego , Estudios Prospectivos , Curación de Fractura/fisiología , Fijación Interna de Fracturas/métodos , Adulto Joven , Persona de Mediana Edad , Resultado del Tratamiento , Ondas UltrasónicasAsunto(s)
Enfermedad de la Arteria Coronaria , Tolerancia al Ejercicio , Isquemia Miocárdica , Índice de Severidad de la Enfermedad , Humanos , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/diagnóstico , Isquemia Miocárdica/fisiopatología , Isquemia Miocárdica/diagnóstico , Prueba de EsfuerzoRESUMEN
AIM: The present study compared the safety, efficacy, and tolerability of the new fixed-dose combination (FDC) of telmisartan 40 mg + bisoprolol 5 mg (TBP) tablets with the existing comparator FDC telmisartan 40 mg + metoprolol succinate ER 50 mg (TMS) tablets in patients with stage 1 and stage 2 hypertension. METHODOLOGY: The multicentric, double-blind, parallel-group, comparative, prospective, phase-III clinical study involved 264 subjects with stage 1 and stage 2 hypertension from 10 centres across India. The selected subjects were randomized into two groups: group A received the TMS and group B received the new FDC TBP. The primary endpoint was the mean change in seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) from baseline to week 12 in both the control and study arms. The secondary endpoint was achieving the target of SeSBP <140 mmHg and SeDBP <90 mmHg from baseline to week 12 in both groups. Safety and tolerability parameters were evaluated in both groups based on adverse effects (AEs) reported by the patients and the physician. RESULTS: Both treatment groups exhibited a reduction in BP after 2 weeks of treatment, which was sustained until 12 weeks. The mean change in SeSBP and SeDBP at weeks 2, 6, and 12 compared to the previous visit showed statistical significance (p < 0.001) in all cases for both groups A and B. The mean changes in SeSBP and SeDBP from baseline to study end were numerically higher in group B than in group A. The mean difference in SeSBP from baseline to study end was significantly higher in group B compared to group A (p = 0.029). By week 12, 88.28 % and 89.84 % of subjects in group B achieved SeSBP <140 mmHg and SeDBP <90 mmHg respectively, while 86.71 % and 91.40 % of subjects in group A achieved the same targets. Reported AEs were mostly mild to moderate in both treatment groups, and no serious AEs or deaths were reported. Tolerability was rated as 'excellent' by 93.75 % of subjects in group B and 91.40 % of subjects in group A. CONCLUSION: Both the new FDC TBP and the existing comparator TMS combination therapy have comparable efficacy, tolerability, and safety for the management of stage 1 and stage 2 hypertension. TRIAL REGISTRY NAME: Clinical Trials Registry of India (CTRI) TRIAL REGISTRATION NO: CTRI/2021/11/037,926 PROTOCOL NO: MLBTL/05/2021 PROTOCOL URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62069&EncHid=&userName=bisoprolol.
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Bisoprolol , Presión Sanguínea , Hipertensión , Metoprolol , Telmisartán , Humanos , Masculino , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Femenino , Bisoprolol/administración & dosificación , Bisoprolol/uso terapéutico , Método Doble Ciego , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Presión Sanguínea/efectos de los fármacos , Telmisartán/administración & dosificación , Telmisartán/uso terapéutico , Metoprolol/administración & dosificación , Metoprolol/uso terapéutico , Benzoatos/administración & dosificación , Benzoatos/uso terapéutico , Bencimidazoles/administración & dosificación , Bencimidazoles/uso terapéutico , India , Relación Dosis-Respuesta a Droga , Antihipertensivos/uso terapéutico , Antihipertensivos/administración & dosificación , Quimioterapia Combinada , Adulto , Combinación de Medicamentos , Estudios de SeguimientoRESUMEN
The rapidly increasing burden of hypertension is responsible for premature deaths from cardiovascular disease (CVD), renal disease, and stroke, with a tremendous public health and financial burden. Hypertension detection, treatment, and control vary worldwide; it is still low, particularly in low- and middle-income countries (LMICs). High blood pressure (BP) and CVD risk have a strong, linear, and independent association. They contribute to alarming numbers of all-cause and CVD deaths. A major culprit for increased hypertension is sympathetic activity, and further complications of hypertension are heart failure, ischemic heart disease (IHD), stroke, and renal failure. Now, antihypertensive interventions have emerged as a global public health priority to reduce BP-related morbidity and mortality. Calcium channel blockers (CCB) are highly effective vasodilators. and the most common drugs used for managing hypertension and CVD. Cilnidipine, with both L- and N-type calcium channel blocking activity, is a promising 4th generation CCB. It causes vasodilation via L-type calcium channel blockade and inhibits the sympathetic nervous system (SNS) via N-type calcium channel blockade. Cilnidipine, which acts as a dual L/N-type CCB, is linked to a reduced occurrence of pedal edema compared to amlodipine, which solely blocks L-type calcium channels. The antihypertensive properties of cilnidipine are very substantial, with low BP variability and long-acting properties. It is beneficial for hypertensive patients to deal with morning hypertension and for patients with abnormal nocturnal BP due to exaggerated sympathetic nerve activation. Besides its BP-lowering effect, it also exhibits organ protection via sympathetic nerve inhibition and renin-angiotensin-aldosterone system inhibition; it controls heart rate and proteinuria. Reno-protective, neuroprotective, and cardioprotective effects of cilnidipine have been well-documented and demonstrated.
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Bloqueadores de los Canales de Calcio , Dihidropiridinas , Hipertensión , Humanos , Hipertensión/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Dihidropiridinas/uso terapéutico , India/epidemiología , Antihipertensivos/uso terapéutico , Consenso , ComorbilidadRESUMEN
BACKGROUND: Limited data exist on the long-term outcomes of transcatheter aortic valve insertion (TAVI) in nonagenarian patients. This study investigated the relationship between patient baseline comorbidity and frailty on the long-term outcome of the nonagenarian population. METHODS: A retrospective analysis was conducted of 187 consecutive nonagenarian patients who underwent TAVI from 2009 to 2020. Multivariable models were used to analyze the association between baseline patient and frailty variables and mortality, stroke, and repeat hospitalization. Long-term survival was compared with an age- and sex-matched United States population. RESULTS: The median Society of Thoracic Surgeons predicted risk of mortality was 10% (interquartile range, 7%-17%). Frailty was met in 72% of patients based on the 5-meter walk test, 13% based on the Kansas City Cardiomyopathy Questionnaire 12-item instrument score, 12% based on Katz Index of Independence in Activities of Daily Living, and 8% based on serum albumin levels. Procedure-related death occurred in 3 patients (2%) and stroke in 8 (4%). The median duration of follow-up was 3.4 years. Outcomes included death in 150 patients (80%), stroke in 15, and repeat hospitalization in 114. Multivariable analysis identified no association between any of the baseline patient variables with mortality, stroke, repeat hospitalization, or the combined outcomes (all P > .05). The 1- and 5-year survival rates in TAVI-treated nonagenarians were similar to age- and sex-matched controls (P = .27). CONCLUSIONS: Long-term death or stroke is independent of The Society of Thoracic Surgeons predicted risk of mortality and frailty risk variables in this nonagenarian patient population who received TAVI. Furthermore, survival is similar to age- and sex-matched controls.
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We evaluated the performance of various polygenic risk score (PRS) models derived from European (EU), South Asian (SA), and Punjabi Asian Indians (AI) studies on 13,974 subjects from AI ancestry. While all models successfully predicted Coronary artery disease (CAD) risk, the AI, SA, and EU + AI were superior predictors and more transportable than the EU model; the predictive performance in training and test sets was 18% and 22% higher in AI and EU + AI models, respectively than in EU. Comparing individuals with extreme PRS quartiles, the AI and EU + AI captured individuals with high CAD risk showed 2.6 to 4.6 times higher efficiency than the EU. Interestingly, including the clinical risk score did not significantly change the performance of any genetic model. The enrichment of diversity variants in EU PRS improves risk prediction and transportability. Establishing population-specific normative and risk factors and inclusion into genetic models would refine the risk stratification and improve the clinical utility of CAD PRS.
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The overall impact of a crude oil spill into a pristine freshwater environment in Canada is largely unknown. To evaluate the impact on the native microbial community, a large-scale in situ model experimental spill was conducted to assess the potential role of the natural community to attenuate hydrocarbons. A small volume of conventional heavy crude oil (CHV) was introduced within contained mesocosm enclosures deployed on the shoreline of a freshwater lake. The oil was left to interact with the shoreline for 72 h and then free-floating oil was recovered using common oil spill response methods (i.e. freshwater flushing and capture on oleophilic absorptive media). Residual polycyclic aromatic hydrocarbon (PAH) concentrations returned to near preoiling concentrations within 2 months, while the microbial community composition across the water, soil, and sediment matrices of the enclosed oligotrophic freshwater ecosystems did not shift significantly over this period. Metagenomic analysis revealed key polycyclic aromatic and alkane degradation mechanisms also did not change in their relative abundance over the monitoring period. These trends suggest that for small spills (<2 l of oil per 15 m2 of surface freshwater), physical oil recovery reduces polycyclic aromatic hydrocarbon concentrations to levels tolerated by the native microbial community. Additionally, the native microbial community present in the monitored pristine freshwater ecosystem possesses the appropriate hydrocarbon degradation mechanisms without prior challenge by hydrocarbon substrates. This study corroborated trends found previously (Kharey et al. 2024) toward freshwater hydrocarbon degradation in an environmentally relevant scale and conditions on the tolerance of residual hydrocarbons in situ.
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Ecosistema , Lagos , Contaminación por Petróleo , Petróleo , Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Petróleo/metabolismo , Lagos/microbiología , Hidrocarburos Policíclicos Aromáticos/metabolismo , Canadá , Contaminantes Químicos del Agua/metabolismo , Biodegradación Ambiental , Sedimentos Geológicos/microbiología , Microbiota/efectos de los fármacos , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Bacterias/clasificación , Agua Dulce/microbiologíaRESUMEN
With the increase in crude oil transport throughout Canada, the potential for spills into freshwater ecosystems has increased and additional research is needed in these sensitive environments. Large enclosures erected in a lake were used as mesocosms for this controlled experimental dilbit (diluted bitumen) spill under ambient environmental conditions. The microbial response to dilbit, the efficacy of standard remediation protocols on different shoreline types commonly found in Canadian freshwater lakes, including a testing of a shoreline washing agent were all evaluated. We found that the native microbial community did not undergo any significant shifts in composition after exposure to dilbit or the ensuing remediation treatments. Regardless of the treatment, sample type (soil, sediment, or water), or type of associated shoreline, the community remained relatively consistent over a 3-month monitoring period. Following this, metagenomic analysis of polycyclic aromatic and alkane hydrocarbon degradation mechanisms also showed that while many key genes identified in PAH and alkane biodegradation were present, their abundance did not change significantly over the course of the experiment. These results showed that the native microbial community present in a pristine freshwater lake has the prerequisite mechanisms for hydrocarbon degradation in place, and combined with standard remediation practices in use in Canada, has the genetic potential and resilience to potentially undertake bioremediation.
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Biodegradación Ambiental , Hidrocarburos , Lagos , Contaminación por Petróleo , Lagos/microbiología , Canadá , Hidrocarburos/metabolismo , Microbiota , Contaminantes Químicos del Agua/metabolismo , Bacterias/genética , Bacterias/metabolismo , Bacterias/clasificación , Hidrocarburos Policíclicos Aromáticos/metabolismo , Sedimentos Geológicos/microbiología , Agua Dulce/microbiología , MetagenómicaRESUMEN
An intriguing effect of short-term caloric restriction (CR) is the expansion of certain stem cell populations, including muscle stem cells (satellite cells), which facilitate an accelerated regenerative program after injury. Here, we utilized the MetRSL274G (MetRS) transgenic mouse to identify liver-secreted plasminogen as a candidate for regulating satellite cell expansion during short-term CR. Knockdown of circulating plasminogen prevents satellite cell expansion during short-term CR. Furthermore, loss of the plasminogen receptor KT (Plg-RKT) is also sufficient to prevent CR-related satellite cell expansion, consistent with direct signaling of plasminogen through the plasminogen receptor Plg-RKT/ERK kinase to promote proliferation of satellite cells. Importantly, we are able to replicate many of these findings in human participants from the CALERIE trial. Our results demonstrate that CR enhances liver protein secretion of plasminogen, which signals directly to the muscle satellite cell through Plg-RKT to promote proliferation and subsequent muscle resilience during CR.
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Plasminógeno , Receptores de Superficie Celular , Ratones , Animales , Humanos , Plasminógeno/metabolismo , Receptores de Superficie Celular/metabolismo , Restricción Calórica , Hígado/metabolismo , Ratones Transgénicos , Serina Proteasas , Proliferación Celular , Músculos/metabolismoRESUMEN
OBJECTIVE: Drug induced sleep endoscopy (DISE) is often performed for pediatric obstructive sleep apnea (OSA) when initial diagnostic studies do not provide adequate information for therapy. However, DISE scoring is subjective and with limitations. This proof-of-concept study demonstrates the use of a novel long-range optical coherence tomography (LR-OCT) system during DISE of two pediatric patients. METHODS: LR-OCT was used to visualize the airway of pediatric patients during DISE. At the conclusion of DISE, the OCT probe was guided in the airway under endoscopic visual guidance, and cross-sectional images were acquired at the four VOTE locations. Data processing involved image resizing and alignment, followed by rendering of three-dimensional (3D) volumetric models of the airways. RESULTS: Two patients were included in this study. Patient one had 18.4%, 20.9%, 72.3%, and 97.3% maximal obstruction at velum, oropharynx, tongue base, and epiglottis, while patient two had 40.2%, 41.4%, 8.0%, and 17.5% maximal obstruction at these regions, respectively. Three-dimensional reconstructions of patients' airways were also constructed from the OCT images. CONCLUSION: This proof-of-concept study demonstrates the successful evaluation of pediatric airway during DISE using LR-OCT, which accurately identified sites and degrees of obstruction with respective 3D airway reconstruction.
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Obstrucción de las Vías Aéreas , Apnea Obstructiva del Sueño , Humanos , Niño , Tomografía de Coherencia Óptica , Polisomnografía , Endoscopía/métodos , Apnea Obstructiva del Sueño/diagnóstico , Sueño , Obstrucción de las Vías Aéreas/diagnóstico por imagen , Obstrucción de las Vías Aéreas/etiologíaRESUMEN
Ensembl (https://www.ensembl.org) is a freely available genomic resource that has produced high-quality annotations, tools, and services for vertebrates and model organisms for more than two decades. In recent years, there has been a dramatic shift in the genomic landscape, with a large increase in the number and phylogenetic breadth of high-quality reference genomes, alongside major advances in the pan-genome representations of higher species. In order to support these efforts and accelerate downstream research, Ensembl continues to focus on scaling for the rapid annotation of new genome assemblies, developing new methods for comparative analysis, and expanding the depth and quality of our genome annotations. This year we have continued our expansion to support global biodiversity research, doubling the number of annotated genomes we support on our Rapid Release site to over 1700, driven by our close collaboration with biodiversity projects such as Darwin Tree of Life. We have also strengthened support for key agricultural species, including the first regulatory builds for farmed animals, and have updated key tools and resources that support the global scientific community, notably the Ensembl Variant Effect Predictor. Ensembl data, software, and tools are freely available.
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Bases de Datos Genéticas , Genómica , Animales , Genoma , Anotación de Secuencia Molecular , Filogenia , Programas Informáticos , HumanosRESUMEN
Semiconductor core/shell quantum dots (QDs) are considered promising building blocks to fabricate photoelectrochemical (PEC) cells for the direct conversion of solar energy into hydrogen (H2). However, the lattice mismatch between core and shell in such QDs results in undesirable defects and severe carrier recombination, limiting photo-induced carrier separation/transfer and solar-to-fuel conversion efficiency. Here, an interface engineering approach is explored to minimize the core-shell lattice mismatch in CdS/CdSexS1-x (x = 0.09-1) core/shell QDs (g-CSG). As a proof-of-concept, PEC cells based on g-CSG QDs yield a remarkable photocurrent density of 13.1 mA cm-2 under AM 1.5 G one-sun illumination (100 mW cm-2), which is ≈54.1% and ≈33.7% higher compared to that in CdS/CdSe0.5S0.5 (g-CSA) and CdS/CdSe QDs (g-CS), respectively. Theoretical calculations and carrier dynamics confirm more efficient carrier separation and charge transfer rate in g-CSG QDs with respect to g-CSA and g-CS QDs. These results are attributed to the minimization of the core-shell lattice mismatch by the cascade gradient shell in g-CSG QDs, which modifies carrier confinement potential and reduces interfacial defects. This work provides fundamental insights into the interface engineering of core/shell QDs and may open up new avenues to boost the performance of PEC cells for H2 evolution and other QDs-based optoelectronic devices.
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Background: Genome-wide polygenic risk scores (PRS) have shown high specificity and sensitivity in predicting type 2 diabetes (T2D) risk in Europeans. However, the PRS-driven information and its clinical significance in non-Europeans are underrepresented. We examined the predictive efficacy and transferability of PRS models using variant information derived from genome-wide studies of Asian Indians (AIs) (PRSAI) and Europeans (PRSEU) using 13,974 AI individuals. Methods: Weighted PRS models were constructed and analyzed on 4602 individuals from the Asian Indian Diabetes Heart Study/Sikh Diabetes Study (AIDHS/SDS) as discovery/training and test/validation datasets. The results were further replicated in 9372 South Asian individuals from UK Biobank (UKBB). We also assessed the performance of each PRS model by combining data of the clinical risk score (CRS). Results: Both genetic models (PRSAI and PRSEU) successfully predicted the T2D risk. However, the PRSAI revealed 13.2% odds ratio (OR) 1.80 [95% confidence interval (CI) 1.63-1.97; p = 1.6 × 10-152] and 12.2% OR 1.38 (95% CI 1.30-1.46; p = 7.1 × 10-237) superior performance in AIDHS/SDS and UKBB validation sets, respectively. Comparing individuals of extreme PRS (ninth decile) with the average PRS (fifth decile), PRSAI showed about two-fold OR 20.73 (95% CI 10.27-41.83; p = 2.7 × 10-17) and 1.4-fold OR 3.19 (95% CI 2.51-4.06; p = 4.8 × 10-21) higher predictability to identify subgroups with higher genetic risk than the PRSEU. Combining PRS and CRS improved the area under the curve from 0.74 to 0.79 in PRSAI and 0.72 to 0.75 in PRSEU. Conclusion: Our data suggest the need for extending genetic and clinical studies in varied ethnic groups to exploit the full clinical potential of PRS as a risk prediction tool in diverse study populations.
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Heterochronic parabiosis (HPB) is known for its functional rejuvenation effects across several mouse tissues. However, its impact on biological age and long-term health is unknown. Here we performed extended (3-month) HPB, followed by a 2-month detachment period of anastomosed pairs. Old detached mice exhibited improved physiological parameters and lived longer than control isochronic mice. HPB drastically reduced the epigenetic age of blood and liver based on several clock models using two independent platforms. Remarkably, this rejuvenation effect persisted even after 2 months of detachment. Transcriptomic and epigenomic profiles of anastomosed mice showed an intermediate phenotype between old and young, suggesting a global multi-omic rejuvenation effect. In addition, old HPB mice showed gene expression changes opposite to aging but akin to several life span-extending interventions. Altogether, we reveal that long-term HPB results in lasting epigenetic and transcriptome remodeling, culminating in the extension of life span and health span.