Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
<span class="paragraphSection">1F012A033J00</span>
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Genetic disease and congenital anomalies continue to be a leading cause of neonate mortality and morbidity. A genetic diagnosis in the neonatal intensive care unit (NICU) can be a challenge given the associated genetic heterogeneity and early stage of a disease. We set out to evaluate the outcomes of Medical Genetics consultation in the NICU in terms of cytogenetic and molecular diagnostic rates and impact on management. We retrospectively reviewed 132 charts from patients admitted to the NICU who received a Medical Genetics diagnostic evaluation over a 2 year period. Of the 132 patients reviewed, 26% (34/132) received a cytogenetic or molecular diagnosis based on the Medical Genetics diagnostic evaluation; only 10% (13/132) received a diagnosis during their admission. The additional 16% (21 patients) received their diagnosis following NICU discharge, but based on a genetic test initiated during hospital-stay. Mean time from NICU admission to confirmed diagnosis was 24 days. For those who received a genetic diagnosis, the information was considered beneficial for clinical management in all, and a direct change to medical management occurred for 12% (4/32). For those non-diagnosed infants seen in out-patient follow-up clinic, diagnoses were made in 8% (3/37). The diagnoses made post-discharge from the NICU comprised a greater number of Mendelian disorders and represent an opportunity to improve genetic care. The adoption of diagnostic tools, such as exome sequencing, used in parallel with traditional approaches will improve rate of diagnoses and will have a significant impact, in particular when the differential diagnosis is broad.
Tuberous sclerosis complex (TSC) is due to pathogenic variants in TSC1 or TSC2 genes resulting in hyperactivation of the mTOR pathway. Many organ systems can be affected, such as brain, skin, eye, heart, bone, kidney, or lung. Sclerotic bone lesions have been reported as frequent findings in TSC although they are not considered diagnostic criteria. The objective of this study is to characterize sclerotic bone lesions detected by chest CT in a large cohort of adult TSC patients and to correlate with genotype. Chest CT scans of 92 adult patients with a definite clinical diagnosis of TSC were reviewed. Sclerotic bone lesions were found in 82 cases (89%) and affected mainly the posterior vertebral elements. Patients without bone lesions had negative mutational studies of TSC1/TSC2 in 86%. Awareness of these lesions in TSC is important to avoid misdiagnosis with osteoblastic metastases.
Costello Syndrome is a rare congenital condition characterized by failure-to-thrive, cardiac abnormalities, distinctive facial features, predisposition to malignant tumors, and developmental delay. In 1999, we analyzed the functional health in a cohort of 18 patients. Since then, a mutation in the HRAS gene has been found to be causative, medical management has been refined, and the level of awareness has increased. The purpose of this study is to compare the functional health outcomes from the 1999 cohort with data prospectively collected from a comparable cohort in 2015. The Pediatric Outcome Data Collection Instrument (PODCI) was administered to parents of children with Costello syndrome during the 2015 International Costello Syndrome Conference. The same instrument and setting were used in the 1999 study. We compared functional health scores from the two groups. A total of 21 participants were included in the 2015 cohort; 15 females (71%) and 6 males (29%). Average age was 5.8 years (range 2–16). When comparing functional health outcomes, we found that the 2015 cohort scored slightly higher in Upper Extremity and Physical Function (57 vs. 54) and Comfort scales (86 vs. 82). However, there was no significant difference in any of the PODCI scales between the two groups. When compared with normative scores, both groups scored significantly lower in every scale except for happiness (p = 0.2952). Despite recent advancements, functional health outcomes in 2015 were similar to those measured in a different cohort in 1999.
Chromosome 7 germline macrodeletions have been implicated in human congenital malformations and developmental delays. We herein report a novel heterozygous macrodeletion of 7q34-q36.3 in a 16-year-old girl originally from West Indies. Similar to previously reported cases of germline chromosome 7q terminal deletions, our patient has dental malposition, and developmental (growth and intellectual) delay. Novel phenotypic features include endemic Kaposi sarcoma (KS), furrowed tongue, thoracolumbar scoliosis, and mild mitral valve dysplasia. The occurrence of human herpes virus 8-driven KS, in a child otherwise normally resistant to other infectious agents and without any other tumoral lesion, points to a very selective immunodeficiency. While defects in organogenesis have been described with such macrodeletions, this is the first report of immunodeficiency and cancer predisposition.
A male child, born from consanguineous parents and having intellectual disability, short stature, dysmorphic facial features, synpolydactyly, and cardiac malformations is reported. Chromosomal microarray analysis showed that the patient presents with an 8p23.1 homozygous deletion, containing the microRNA miR-4660, the exoribonuclease 1 (ERI1), and malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) genes. The microRNA miR-4660 has no known function. MFHAS1 is an immunomodulatory protein involved in Toll-like receptor signaling, erythropoiesis, and cancer. ERI1 is a ribonuclease involved in RNA metabolism and is required for the correct patterning of the skeleton by defining the HOXC8 expression. We discuss the involvement of these deleted genes to the patient's features and highlight differential diagnoses with syndromes implicating limb extremity abnormalities such as synpolydactyly, including the monosomy 8p.
Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by prominent trabecular meshwork, and it is thought to result from arrest of the normal compaction process during embryogenesis. Patients with LVNC may be asymptomatic or have symptoms ranging from heart failure to stroke, life-threatening arrhythmias, or sudden death. The frequency of LVNC in children has increased with longer clinical courses. About 80% of patients with trisomy 13 have a congenital cardiac abnormality, but a clinical description of LVNC with trisomy 13 is lacking because of its poor prognosis and lack of awareness about LVNC. We described a patient with trisomy 13 who was diagnosed with LVNC-dilated phenotype and died suddenly, as well as two additional patients with LVNC. All three patients had chronic heart failure without congenital heart disease and were treated with diuretics. To manage trisomy 13 with or without congenital heart disease, cardiac disease such as LVNC may present at any ages, and therefore cardiac evaluation should be considered as a part of their appropriate management.
Pre-eclampsia (PE) remains a disease of theories despite extensive research into its etiology. Alteration in the production of vascular endothelial growth factor (VEGF), a biomarker of endothelial dysfunction,...
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Obese individuals differ in their risk of developing metabolic and cardiovascular complications depending on fat distribution (subcutaneous versus visceral) and adipose tissue (AT) phenotype (hyperplasic versu...
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Reports on the effect of age and obesity on myocardial ischaemia/reperfusion (I/R) injury and ischaemic preconditioning are contradictory. The aim of this study was to re-evaluate the effects of age and diet-i...
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In preparation for migration from freshwater to marine habitats, Atlantic salmon (Salmo salar L.) undergo smoltification, a transformation that includes the acquisition of hyposmoregulatory capacity. The growth h...
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To investigate the anti-inflammatory effects of specific small interfering RNA targeting NF-κB on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats.
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Transcranial magnetic stimulation (TMS) represents a painless and non-invasive method to study the motor system. TMS has become extensively used worldwide, for example in healthy humans to investigate mechanisms of brain plasticity in the primary motor cortex (M1) (Delvendahl et al., 2012) and to probe the neurophysiological underpinnings of M1 function (Reis et al., 2008). Also, TMS-related measures are used clinically for diagnostic, prognostic and evaluative purposes in different pathologies, such as stroke (Liepert et al., 2000a; Liepert et al., 2000b; Talelli et al., 2006).
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Different seizure-onset patterns (SOP) have been described in intracranial EEG. A recent meta-analysis demonstrated the variety of SOPs in focal epilepsy, and concluded that low-voltage fast activity (LVF) is overall the most common, whereas high-amplitude low-frequency periodic spiking (PS) is the most prevalent in mesiotemporal lobe epilepsy (mTLE) (Singh et al., 2015). In a large series of patients with refractory focal epilepsy due to different pathologies, our group identified seven different intracerebral SOPs (Perucca et al., 2014).
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Some common disorders of the peripheral nervous system are closely linked to a monoclonal gammopathy.Peripheral neuropathy associated with monoclonal gammopathy is an uncommon but important cause of neuropathy that may stem from a grave underlying disorder (Ramchandren and Lewis 2012). It has long been demonstrated that myelin-associated glycoprotein (MAG) behaves as a self-antigen in patients with polyneuropathy and IgM monoclonal gammopathy (Joint Task Force of the EFNS and the PNS 2010; Magy et al.
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The present paper characterizes the attachment ability of males and females of Nezara viridula (Heteroptera: Pentatomidae) on artificial surfaces (smooth hydrophilic, smooth hydrophobic, different surface roughness) and on both leaf surfaces of the typical host plant species Vicia faba, using a centrifugal force tester and a traction force experiments set up. N. viridula is a serious crop pest in the world and shows attachment devices different from the so far investigated Heteroptera, with a tarsus characterized by distal smooth flexible pulvilli combined with claws and proximal ventral hairy pad. Notwithstanding the different body mass between the sexes, no difference was found between friction forces generated by females and males. Friction force was higher on hydrophilic surfaces than on hydrophobic ones and was lower on both sides of V. faba leaf compared with both hydrophilic and hydrophobic artificial smooth surfaces. On the surfaces with different roughness, the friction force values varied significantly, with the higher attachment ability on the surface with very high asperity size followed by the smooth surface. The lowest attachment was on the surfaces with intermediate asperity sizes. These results could be related to the specific combination of attachment devices of N. viridula.
In many sports, athletes have a preferred leg for sport-specific tasks, such as jumping, which leads to strength differences between both legs, yet the underlying changes in force-generating mechanical properties of the muscle remain unknown. The purpose of this study was to investigate whether the muscle architecture of the medial gastrocnemius (MG) is different between both legs in well-trained jumping athletes and untrained individuals. In addition, we investigated the effect of two ankle joint positions on ultrasound muscle architecture measurements.
Muscle architecture of both legs was measured in 16 athletes and 11 untrained individuals at two ankle joint angles: one with the ankle joint in a tendon slack length (TSL) angle and one in a 90° angle.
Fascicle lengths and pennation angles at TSL were not different between the preferred and non-preferred legs in either group. The comparison between groups showed no difference in fascicle length, but greater pennation angles were found in the athletes (21.7° ± 0.5°) compared to the untrained individuals (19.8° ± 0.6°). Analyses of the muscle architecture at a 90° angle yielded different results, mainly in the comparison between groups.
These results provide only partial support for the notion of training-induced changes in muscle architecture as only differences in pennation angles were found between athletes and untrained individuals. Furthermore, our results provide support to the recommendation to take into account the tension–length relationship and to measure muscle architecture at individually determined tendon slack joint angles.
The aim of the present study was to compare the energy expenditure (EE) during and after two treadmill protocols, high-intensity interval training (HIIT) and moderate continuous training (CONT), in young adult men.
The sample was comprised by 26 physically active men aged between 18 and 35 years engaged in aerobic training programs. They were divided into two groups: HIIT (n = 14) which performed eight 20 s bouts at 130% of the velocity associated with the maximal oxygen consumption on a treadmill with 10 s of passive rest, or CONT (n = 12) which performed 30 min running on a treadmill at a submaximal velocity equivalent to 90–95% of the heart rate associated with the anaerobic threshold. Data related to oxygen consumption ( \(\dot{V}{\text{O}}_{2}\) ) and EE were measured during the protocols and the excess post-exercise oxygen consumption (EPOC) was calculated for both sessions.
No difference was found between groups for mean \(\dot{V}{\text{O}}_{2}\) (HIIT: 2.84 ± 0.46 L min−1; CONT: 2.72 ± 0.43 L min−1) and EE per minute (HIIT: 14.36 ± 2.34 kcal min−1; CONT: 13.21 ± 2.08 kcal min−1) during protocols. Regarding total EE during session, CONT resulted in higher values compared to HIIT (390.45 ± 65.15; 55.20 ± 9.33 kcal, respectively). However, post-exercise EE and EPOC values were higher after HIIT (69.31 ± 10.88; 26.27 ± 2.28 kcal, respectively) compared to CONT (55.99 ± 10.20; 13.43 ± 10.45 kcal, respectively).
These data suggest that supramaximal HIIT has a higher impact on EE and EPOC in the early phase of recovery when compared to CONT.
The use of pattern recognition-based methods to control myoelectric upper-limb prostheses has been well studied in individuals with high-level amputations but few studies have demonstrated that it is suitable ...
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It is quite difficult to evaluate ataxic gait quantitatively in clinical practice. The aim of this study was to analyze the characteristics of ataxic gait using a triaxial accelerometer and to develop a novel ...
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The present paper describes the design and evaluation of an automated version of the Modified Jebsen Test of Hand Function (MJT) based on the Microsoft Kinect sensor.
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Deficits of kinesthesia (limb position and movement sensation) commonly limit sensorimotor function and its recovery after neuromotor injury. Sensory substitution technologies providing synthetic kinesthetic f...
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Powered ankle-foot exoskeletons can reduce the metabolic cost of human walking to below normal levels, but optimal assistance properties remain unclear. The purpose of this study was to test the effects of dif...
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Microbial Drug Resistance , Vol. 0, No. 0.
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Another intubation tip from Williamson County EMS.
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Another intubation tip from Williamson County EMS.
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Steve Whitehead, host of Remember 2 Things, discusses coping mechanisms for EMS providers dealing with ongoing stress.
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Another intubation tip from Williamson County EMS.
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Steve Whitehead, host of Remember 2 Things, discusses coping mechanisms for EMS providers dealing with ongoing stress.
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Another intubation tip from Williamson County EMS.
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Steve Whitehead, host of Remember 2 Things, discusses coping mechanisms for EMS providers dealing with ongoing stress.
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Steve Whitehead, host of Remember 2 Things, discusses coping mechanisms for EMS providers dealing with ongoing stress.
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The spectrum of congenital anomalies affecting either the upper tract (kidneys and ureters) or lower tract (reproductive organs) of the genitourinary (GU) system are fundamentally linked by the developmental origin of multiple GU tissues, including the kidneys, gonads, and reproductive ductal systems: the intermediate mesoderm. Although ∼31% of DiGeorge/del22q11.2 syndrome...
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Publication date: Available online 9 May 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Stefano Carda, Andrea Biasiucci, Andrea Maesani, Silvio Ionta, Julien Moncharmont, Stephanie Clarke, Micah M. Murray, José del R. Millán
ObjectiveTo evaluate the effects of electrically assisted movement therapy (EAMT) in which patients use functional electrical stimulation, modulated by a custom device controlled through the patient's unaffected hand, to produce or assist task-specific upper limb movements, which enables them to engage in intensive goal-oriented training.DesignRandomized, crossover, assessor-blinded, 5-week trial with follow-up at 18 weeks.SettingRehabilitation university hospital.ParticipantsPatients with chronic, severe stroke (N=11; mean age, 47.9y) more than 6 months poststroke (mean time since event, 46.3mo).InterventionsBoth EAMT and the control intervention (dose-matched, goal-oriented standard care) consisted of 10 sessions of 90 minutes per day, 5 sessions per week, for 2 weeks. After the first 10 sessions, group allocation was crossed over, and patients received a 1-week therapy break before receiving the new treatment.Main Outcome MeasuresFugl-Meyer Motor Assessment for the Upper Extremity, Wolf Motor Function Test, spasticity, and 28-item Motor Activity Log.ResultsForty-four individuals were recruited, of whom 11 were eligible and participated. Five patients received the experimental treatment before standard care, and 6 received standard care before the experimental treatment. EAMT produced higher improvements in the Fugl-Meyer scale than standard care (P<.05). Median improvements were 6.5 Fugl-Meyer points and 1 Fugl-Meyer point after the experimental treatment and standard care, respectively. The improvement was also significant in subjective reports of quality of movement and amount of use of the affected limb during activities of daily living (P<.05).ConclusionsEAMT produces a clinically important impairment reduction in stroke patients with chronic, severe upper limb paresis.
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United Hatzalah of Israel JERUSALEM — In an effort to raise awareness and create a stronger visual presence in the community, United Hatzalah has rebranded its vehicles and uniforms utilizing a new logo and embracing the color orange which has been widely understood as representing the organization's 3,200 EMS volunteers around the country. While explaining the choice of why the organization ...
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background.</strong> Myocardial injury after non-cardiac surgery (MINS), a complication with unclear pathogenesis, occurs within the first 30 days after surgery and worsens prognosis. Hypercoagulability induced by surgery might contribute to plaque rupture, with subsequent thrombosis and myocardial injury. This study assessed haemostatic markers before surgery and evaluated their association with MINS.<strong>Methods.</strong> This is a substudy of VISION, a prospective cohort study of perioperative cardiovascular events. Of 475 consecutive vascular surgery patients, 47 (9.9%) developed MINS, defined as postoperative high-sensitivity troponin ≥50 ng litre<sup>−1</sup>, with ≥20% elevation from the preoperative concentration. The control group consisted of 84 non-MINS patients matched for patient characteristics and co-morbidities. The following preoperative markers of hypercoagulability and fibrinolysis were measured: antithrombin, factor VIII activity, von Willebrand factor concentration and activity, fibrinogen, D-dimer, plasmin–antiplasmin complex, and tissue plasminogen activator. Moreover, C-reactive protein and CD40L concentrations were measured to assess inflammatory activity.<strong>Results.</strong> Patients with MINS compared with the non-MINS group had a significantly higher concentration of factor VIII (186 <span style="font-style:italic;">vs</span> 155%, <span style="font-style:italic;">P</span>=0.006), von Willebrand factor activity (223 <span style="font-style:italic;">vs</span> 160%, <span style="font-style:italic;">P</span><0.001), von Willebrand factor concentration (317 <span style="font-style:italic;">vs</span> 237%, <span style="font-style:italic;">P</span>=0.02), concentrations of fibrinogen (5.6 <span style="font-style:italic;">vs</span> 4.2 g litre<sup>−1</sup>, <span style="font-style:italic;">P</span>=0.03), D-dimer (1680.0 <span style="font-style:italic;">vs</span> 1090.0 ng ml<sup>−1</sup>, <span style="font-style:italic;">P</span>=0.04), plasmin–antiplasmin complex (747 <span style="font-style:italic;">vs</span> 512 ng ml<sup>−1</sup>, <span style="font-style:italic;">P</span>=0.002) and C-reactive protein (10 <span style="font-style:italic;">vs</span> 4.5 mg litre<sup>−1</sup>, <span style="font-style:italic;">P</span>=0.02) but not antithrombin (95 <span style="font-style:italic;">vs</span> 94%, <span style="font-style:italic;">P</span>=0.89), tissue plasminogen activator (11 <span style="font-style:italic;">vs</span> 9.7 ng ml<sup>−1</sup>, <span style="font-style:italic;">P</span>=0.06) and CD40L (8790 <span style="font-style:italic;">vs</span> 8580 pg ml<sup>−1</sup>, <span style="font-style:italic;">P</span>=0.73).<strong>Conclusions.</strong> Preoperative elevation of blood markers of hypercoagulability in patients undergoing vascular surgery is associated with a higher risk of MINS.<strong>Clinical trial registration.</strong> NCT00512109.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background.</strong> Machine-generated indices based on quantitative electroencephalography (EEG), such as the patient state index (PSI™) and burst-suppression ratio (BSR), are increasingly being used to monitor intraoperative depth of anaesthesia in the endeavour to improve postoperative neurological outcomes, such as postoperative delirium (POD). However, the accuracy of the BSR compared with direct visualization of the EEG trace with regard to the prediction of POD has not been evaluated previously.<strong>Methods.</strong> Forty-one consecutive patients undergoing non-cardiac, non-intracranial surgery with general anaesthesia wore a SedLine<sup>®</sup> monitor during surgery and were assessed after surgery for the presence of delirium with the Confusion Assessment Method. The intraoperative EEG was scanned for absolute minutes of EEG suppression and correlated with the incidence of POD. The BSR and PSI™ were compared between patients with and without POD.<strong>Results.</strong> Visual analysis of the EEG by neurologists and the SedLine<sup>®</sup>-generated BSR provided a significantly different distribution of estimated minutes of EEG suppression (<span style="font-style:italic;">P</span>=0.037). The Sedline<sup>®</sup> system markedly underestimated the amount of EEG suppression. The number of minutes of suppression assessed by visual analysis of the EEG was significantly associated with POD (<span style="font-style:italic;">P</span>=0.039), whereas the minutes based on the BSR generated by SedLine<sup>®</sup> were not associated with POD (<span style="font-style:italic;">P</span>=0.275).<strong>Conclusions.</strong> Our findings suggest that SedLine<sup>®</sup> (machine)-generated indices might underestimate the minutes of EEG suppression, thereby reducing the sensitivity for detecting patients at risk for POD. Thus, the monitoring of machine-generated BSR and PSI™ might benefit from the addition of a visual tracing of the EEG to achieve a more accurate and real-time guidance of anaesthesia depth monitoring and the ultimate goal, to reduce the risk of POD.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background:</strong> The study aimed to determine whether a patient's choice for their intrathecal morphine (ITM) dose reflects their opioid requirements and pain after caesarean delivery and if giving women a choice of ITM dose would reduce opioid use and improve pain scores compared with women who did not have a choice.<strong>Methods:</strong> A total of 120 women undergoing caesarean delivery with spinal anaesthesia were enrolled in this randomized, double-blind study. Patients were randomly assigned to a choice of 100 or 200 μg ITM or no choice. The study involved deception, such that all participants were still randomly assigned 100 or 200 μg ITM regardless of choice. Rescue opioid use over the 48-h study period was the primary outcome measure. Pain at rest and movement and side effect (pruritus, nausea, and vomiting) data were collected 3, 6, 12, 24, 36 and 48 h postoperatively. Data are presented as median [95% confidence interval (CI)].<strong>Results:</strong> Women who requested the larger ITM dose required more supplemental opioid [median 0.8 (95% CI 0.4–1.3)] mg morphine equivalents at each assessment interval; <span style="font-style:italic;">P</span> < 0.001] and reported more pain with movement [median 1.2 (95% CI 0.5–1.9)] verbal numerical rating score of 0–10 points] than patients who requested the smaller ITM dose (<span style="font-style:italic;">P</span> = 0.0008), regardless of the ITM dose given. There was no difference in opioid use whether the patient was offered a perceived choice or not.<strong>Conclusions:</strong> Women who were given a choice and chose the larger ITM dose correctly anticipated a greater postoperative opioid requirement and more pain compared with women who chose the smaller dose. Simply being offered a choice did not impact opioid use or pain scores after caesarean delivery.<strong>Trial Registration:</strong> ClinicalTrials.gov (NCT01425762).</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background:</strong> Caudal block is commonly administered for postoperative analgesia in children. Although caudal block with 1.5 ml kg<sup>−1</sup> local anaesthetic has been reported to reduce cerebral oxygenation in infants, the effect of caudal block on intracranial pressure (ICP) in children has not been well investigated. Optic nerve sheath diameter (ONSD) correlates with degree of ICP. This study aimed to estimate the effects of caudal block on ICP according to volume of local anaesthetic using ultrasonographic measurement of ONSD in children.<strong>Methods:</strong> Eighty patients, 6- to 48-months-old, were randomly allocated to the high-volume (HV) or low-volume (LV) groups for caudal block with ropivacaine 0.15%, 1.5 ml kg<sup>−1</sup> or 1.0 ml kg<sup>−1</sup>, respectively. Measurement of ONSD was performed before (T0), immediately after (T1), and 10 min (T2) and 30 min (T3) after caudal block.<strong>Results:</strong> The two groups exhibited significant differences in ONSD according to time (<span style="font-style:italic;">P</span><sub>Group x Time</sub>=0.003). The HV group exhibited significantly greater changes in ONSD from T0 to T2 and T3 than the LV group. However, in both groups, ONSDs at T1, T2 and T3 were significantly greater compared with those at T0, with the highest values at T2.<strong>Conclusions:</strong> Caudal block with a high volume of local anaesthetic can cause a greater increase in ICP than caudal block with a low volume of local anaesthetic. However, caudal block with 1.0 ml kg<sup>−1</sup> of local anaesthetic can also result in a significant increase in ICP.<strong>Clinical trial registration.</strong> NCT02768493.</span>
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Classical Ehlers-Danlos syndrome (cEDS) is characterized by marked cutaneous involvement that is defined by many criteria of the Villefranche nosology and the 2017 revision. However, the diagnostic flow-chart that prompts molecular testing is still based on experts' opinion rather than systematic published data. Here we report on 62 molecularly characterized cEDS patients with focus on skin, mucosae, face, and joint hypermobility. The major and minor Villefranche criteria, additional 11 mucocutaneous signs and 15 facial dysmorphic traits were ascertained and feature rates compared by sex and age. In our cohort, we did not observe any mandatory clinical sign, skin hyperextensibility plus atrophic scars was the most frequent combination, whereas generalized joint hypermobility according to the Beighton score decreased with age. Skin was more commonly hyperextensible on elbows, neck, and knees. The sites more frequently affected by abnormal atrophic scar patterning included knees, face (especially forehead), pretibial area, and elbows. Facial dysmorphism commonly affected midface/orbital areas with epicanthal folds and infraorbital creases more common in young patients. The combination of ≥1 eye dysmorphism and facial/forehead scars may support the diagnosis in children. Minor acquired traits, such as molluscoid pseudotumors, subcutaneous spheroids, and signs of premature skin aging are equally useful in adults.
Clinical features of pediatric and adult patients with classical Ehlers Danlos syndrome
It has been suggested that matrix metalloproteinase (MMP) polymorphisms are associated with the pathogenesis of aortic aneurysmal diseases. In this study, we conducted a systematic review with an update meta-analysis to investigate the relationship between MMP family polymorphisms and aortic aneurysmal diseases. We systematically reviewed 24 polymorphisms in eight MMP genes related to the risk of abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA) or thoracic aortic dissection (TAD). A total of 19 case–control studies with 15 highly studied MMP polymorphisms were included in our meta-analysis. Our results suggested that MMP2rs243865, MMP3rs3025058, MMP13rs2252070 polymorphisms were significantly associated with AAA risk, MMP2rs11643630, MMP8rs11225395 polymorphisms were correlated with TAD risk, and MMP9rs3918242 under the dominant model could increase AAA risk in hospital-based (HB) subgroup. No associations with aortic aneurysmal diseases were identified for other polymorphisms assessed in our meta-analysis. In summary, some studied MMP polymorphisms associated with the risk of aortic aneurysmal diseases are potential predictive biomarkers for the clinical application. Moreover, other MMP polymorphisms with limited studies but relevant to aortic aneurysmal formation and progression need further prospective and large investigations to confirm results.
A systematic review and meta-analysis for the association of MMPs polymorphisms with the risk of aortic aneurysmal disease.
Turner syndrome (TS), characterized by short stature and premature ovarian failure, is caused by chromosomal aberrations with total or partial loss of one of the two X chromosomes. Spontaneous puberty, menarche, and pregnancy occur in some patients depending on the abnormality of the X. Moreover, spontaneous pregnancy is uncommon (<0.5%) for TS with 45,X monosomy. Among TS patients, 45,X/47,XXX karyotype is extremely rare. Previous reports have demonstrated that TS with 45,X/47,XXX is less severe than common TS due to higher occurrence of puberty (83%), menarche (57–67%), and fertility (14%) and lower occurrence of congenital anomalies (<5%). However, TS mosaicism may not reduce the frequency of short stature. We diagnosed a 10-year-girl with TS with 45,X/47,XXX mosaicism who presented with short stature. She showed mild TS phenotype including short stature but had spontaneous puberty. Based on our case and previous reports, we expect that girls with 45,X/47,XXX mosaicism may progress through puberty normally, without estrogen therapy. Therefore, it is necessary to consider specific guidelines for clinical decisions surrounding pubertal development and fertility in TS with 45,X/47,XXX karyotype.
The hippocampus is a brain region in the temporal lobe that supports learning and memory. The first stage of hippocampal processing occurs in the dentate gyrus (DG), a region that has long perplexed and tantalized researchers because of its striking quiet.
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The localization of motor unit territories provides an anatomical basis to suggest that the CNS may have more independence in motor unit recruitment and control strategies than what was previously thought. In this study, we investigated whether the human spinal cord has the neuromuscular circuitry to independently activate motor units located in different regions of the vastus medialis.
Mechanical taps were applied to multiple locations in the vastus medialis (VM) in nine healthy individuals. Regional responses within the muscle were observed using a grid of 5 × 13 surface EMG electrodes. The EMG amplitude was quantified for each channel, and a cluster of channels showing the largest activation was identified. The spatial location of the EMG response was quantified as the position of the channels in the cluster. In a subset of 3 participants, intramuscular recordings were performed simultaneously with the surface EMG recordings.
Mechanical taps resulted in localized, discrete responses for each participant. The spatial location of the elicited responses was dependent on the location of the tap (P < 0.001). Recordings with intramuscular electrodes confirmed the regional activation of the VM for different tap locations.
Selective stimulation of 1a afferents localized in a region of the VM results in reflex recruitment of motor units in the same region. These findings suggest that the human spinal cord has the neuromuscular circuitry to modulate spatially the motoneuronal output to vastus medialis regions, which is a neuroanatomical prerequisite for regional activation.
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Chest wall strapping has been used to assess mechanisms of dyspnea with restrictive lung disease. This study examined the hypothesis that dyspnea with restriction depends principally on the degree of reflex ventilatory stimulation. We compared dyspnea at the same (iso)ventilation when added dead space provided a component of the ventilatory stimulus during exercise. Eleven healthy men undertook a randomized controlled crossover trial that compared four constant work exercise conditions: 1) control (CTRL): unrestricted breathing at 90% gas exchange threshold (GET); 2) CTRL+dead space (DS): unrestricted breathing with 0.6-l dead space, at isoventilation to CTRL due to reduced exercise intensity; 3) CWS: chest wall strapping at 90% GET; and 4) CWS+DS: chest strapping with 0.6-l dead space, at isoventilation to CWS with reduced exercise intensity. Chest strapping reduced forced vital capacity by 30.4 ± 2.2% (mean ± SE). Dyspnea at isoventilation was unchanged with CTRL+DS compared with CTRL (1.93 ± 0.49 and 2.17 ± 0.43, 0–10 numeric rating scale, respectively; P = 0.244). Dyspnea was lower with CWS+DS compared with CWS (3.40 ± 0.52 and 4.51 ± 0.53, respectively; P = 0.003). Perceived leg fatigue was reduced with CTRL+DS compared with CTRL (2.36 ± 0.48 and 2.86 ± 0.59, respectively; P = 0.049) and lower with CWS+DS compared with CWS (1.86 ± 0.30 and 4.00 ± 0.79, respectively; P = 0.006). With unrestricted breathing, dead space did not change dyspnea at isoventilation, suggesting that dyspnea does not depend on the mode of reflex ventilatory stimulation in healthy individuals. With chest strapping, dead space presented a less potent stimulus to dyspnea, raising the possibility that leg muscle work contributes to dyspnea perception independent of the ventilatory stimulus.
NEW & NOTEWORTHY Chest wall strapping was applied to healthy humans to simulate restrictive lung disease. With chest wall strapping, dyspnea was reduced when dead space substituted for part of a constant exercise stimulus to ventilation. Dyspnea associated with chest wall strapping depended on the contribution of leg muscle work to ventilatory stimulation. Chest wall strapping might not be a clinically relevant model to determine whether an alternative reflex ventilatory stimulus mimics the intensity of exertional dyspnea.
We investigate the influence of bifurcation geometry, asymmetry of daughter airways, surfactant distribution, and physicochemical properties on the uniformity of airway recruitment of asymmetric bifurcating airways. To do so, we developed microfluidic idealized in vitro models of bifurcating airways, through which we can independently evaluate the impact of carina location and daughter airway width and length. We explore the uniformity of recruitment and its relationship to the dynamic surface tension of the lining fluid and relate this behavior to the hydraulic (PHyd) and capillary (PCap) pressure drops. These studies demonstrate the extraordinary importance of PCap in stabilizing reopening, even in highly asymmetric systems. The dynamic surface tension of pulmonary surfactant is integral to this stability because it modulates PCap in a velocity-dependent manner. Furthermore, the surfactant distribution at the propagating interface can have a very large influence on recruitment stability by focusing surfactant preferentially to specific daughter airways. This implies that modification of the surfactant distribution through novel modes of ventilation could be useful in inducing uniformly recruited lungs, aiding in gas exchange, and reducing ventilator-induced lung injury.
NEW & NOTEWORTHY The dynamic surface tension of pulmonary surfactant is integral to the uniformity of asymmetric bifurcation airway recruitments because it modulates capillary pressure drop in a velocity-dependent manner. Also, the surfactant distribution at the propagating interface can have a very large influence on recruitment stability by focusing surfactant preferentially to specific daughter airways. This implies that modification of the surfactant distribution through novel modes of ventilation could be useful in inducing uniformly recruited lungs, reducing ventilator-induced lung injury.
Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans. Twenty-eight healthy, middle-aged, sedentary men were randomized for 2 wk of HIIT or MICT. Intestinal insulin-stimulated glucose uptake and fasting free fatty acid uptake from circulation were measured using positron emission tomography and [18F]FDG and [18F]FTHA. In addition, effects of HIIT and MICT on intestinal GLUT2 and CD36 protein expression were studied in rats. Training improved aerobic capacity (P = 0.001) and whole body insulin sensitivity (P = 0.04), but not differently between HIIT and MICT. Insulin-stimulated glucose uptake increased only after the MICT in the colon (HIIT = 0%; MICT = 37%) (P = 0.02 for time x training) and tended to increase in the jejunum (HIIT = –4%; MICT = 13%) (P = 0.08 for time x training). Fasting free fatty acid uptake decreased in the duodenum in both groups (HIIT = –6%; MICT = –48%) (P = 0.001 time) and tended to decrease in the colon in the MICT group (HIIT = 0%; MICT = –38%) (P = 0.08 for time x training). In rats, both training groups had higher GLUT2 and CD36 expression compared with control animals. This study shows that already 2 wk of MICT enhances insulin-stimulated glucose uptake, while both training modes reduce fasting free fatty acid uptake in the intestine in healthy, middle-aged men, providing an additional mechanism by which exercise training can improve whole body metabolism.
NEW & NOTEWORTHY This is the first study where the effects of exercise training on the intestinal substrate uptake have been investigated using the most advanced techniques available. We also show the importance of exercise intensity in inducing these changes.
Multipotent cells have received great interest because of their potential capacity to repair and remodel peripheral tissues. We examined the effect of an acute exercise bout on the number of circulating cells with known remodeling properties and the level of factors in plasma and skeletal muscle tissue with potential to recruit these cells. Twenty healthy male subjects performed a 60-min cycling exercise. Blood samples for flow cytometry were drawn from 10 subjects (group 1) before and up to 2 h after exercise, and absolute cell counts of the classical (CD14++CD16–), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocyte (MO) subpopulations and of CD45dimCD34+VEGFR2+ endothelial progenitor cells (EPCs) were measured by bead-based determination. Plasma samples and vastus lateralis muscle biopsies were obtained from the other 10 subjects (group 2). In group 1, all MO subsets were increased directly after exercise, with CD14+CD16++ MOs showing the greatest fold increase. After 2 h, only CD14++CD16– MOs were increased compared with resting levels. The number of EPCs showed a trend toward increasing with exercise (P = 0.08). In group 2, the mRNA levels of the endothelial adhesion molecules ICAM-1, VCAM-1, and E-selectin increased in the skeletal muscle tissue. VEGF-A increased in exercised skeletal muscle and stimulated the expression of VCAM-1 and E-selectin in human umbilical vein endothelial cells. In conclusion, exercise increases MO subsets with different temporal patterns and enhances the capacity of skeletal muscle tissue to recruit circulating cells as shown by increased expression of endothelial adhesion molecules.
NEW & NOTEWORTHY In the present study we showed for the first time that the adhesion molecules ICAM-1, VCAM-1, and E-selectin, known to be able to recruit circulating cells to the peripheral tissue, increased in exercised human skeletal muscle concurrently with increased circulating levels of cells shown to have importance for skeletal muscle remodeling. These findings support the concept of cell recruitment from the circulation playing a role in skeletal muscle adaptation to exercise.
Noisy stimuli, along with linear systems analysis, have proven to be effective for mapping functional neural connections. We explored the use of noisy (10–115 Hz) Achilles tendon vibration to examine somatosensory reflexes in the triceps surae muscles in standing healthy young adults (n = 8). We also examined the association between noisy vibration and electrical activity recorded over the sensorimotor cortex using electroencephalography. We applied 2 min of vibration and recorded ongoing muscle activity of the soleus and gastrocnemii using surface electromyography (EMG). Vibration amplitude was varied to characterize reflex scaling and to examine how different stimulus levels affected postural sway. Muscle activity from the soleus and gastrocnemii was significantly correlated with the tendon vibration across a broad frequency range (~10–80 Hz), with a peak located at ~40 Hz. Vibration-EMG coherence positively scaled with stimulus amplitude in all three muscles, with soleus displaying the strongest coupling and steepest scaling. EMG responses lagged the vibration by ~38 ms, a delay that paralleled observed response latencies to tendon taps. Vibration-evoked cortical oscillations were observed at frequencies ~40–70 Hz (peak ~54 Hz) in most subjects, a finding in line with previous reports of sensory-evoked -band oscillations. Further examination of the method revealed 1) accurate reflex estimates could be obtained with <60 s of low-level (root mean square = 10 m/s2) vibration; 2) responses did not habituate over 2 min of exposure; and importantly, 3) noisy vibration had a minimal influence on standing balance. Our findings suggest noisy tendon vibration is an effective novel approach to characterize somatosensory reflexes during standing.
NEW & NOTEWORTHY We applied noisy (10–115 Hz) vibration to the Achilles tendon to examine the frequency characteristics of lower limb somatosensory reflexes during standing. Ongoing muscle activity was coherent with the noisy vibration (peak coherence ~40 Hz), and coherence positively scaled with increases in stimulus amplitude. Our findings suggest that noisy tendon vibration, along with linear systems analysis, is an effective novel approach to study somatosensory reflex actions in active muscles.
To improve the pathophysiological understanding of visual changes observed in astronauts, we aimed to use quantitative MRI to measure anatomic and physiological responses during a ground-based spaceflight analog (head-down tilt, HDT) combined with increased ambient carbon dioxide (CO2). Six healthy, male subjects participated in the double-blinded, randomized crossover design study with two conditions: 26.5 h of –12° HDT with ambient air and with 0.5% CO2, both followed by 2.5-h exposure to 3% CO2. Volume and mean diffusivity quantification of the lateral ventricle and phase-contrast flow sequences of the internal carotid arteries and cerebral aqueduct were acquired at 3 T. Compared with supine baseline, HDT (ambient air) resulted in an increase in lateral ventricular volume (P = 0.03). Cerebral blood flow, however, decreased with HDT in the presence of either ambient air or 0.5% CO2 (P = 0.002 and P = 0.01, respectively); this was partially reversed by acute 3% CO2 exposure. Following HDT (ambient air), exposure to 3% CO2 increased aqueductal cerebral spinal fluid velocity amplitude (P = 0.01) and lateral ventricle cerebrospinal fluid (CSF) mean diffusivity (P = 0.001). We concluded that HDT causes alterations in cranial anatomy and physiology that are associated with decreased craniospinal compliance. Brief exposure to 3% CO2 augments CSF pulsatility within the cerebral aqueduct and lateral ventricles.
NEW & NOTEWORTHY Head-down tilt causes increased lateral ventricular volume and decreased cerebrovascular flow after 26.5 h. Additional short exposure to 3% ambient carbon dioxide levels causes increased cerebrovascular flow associated with increased cerebrospinal fluid pulsatility at the cerebral aqueduct. Head-down tilt with chronically elevated 0.5% ambient carbon dioxide and acutely elevated 3% ambient carbon dioxide causes increased mean diffusivity of cerebral spinal fluid within the lateral ventricles.
The dynamic response to a stimulus such as exercise can reveal valuable insights into systems control in health and disease that are not evident from the steady-state perturbation. However, the dynamic response profile and kinetics of cerebrovascular function have not been determined to date. We tested the hypotheses that bilateral middle cerebral artery blood flow mean velocity (MCAV) increases exponentially following the onset of moderate-intensity exercise in 10 healthy young subjects. The MCAV response profiles were well fit to a delay (TD) + exponential (time constant, ) model with substantial agreement for baseline [left (L): 69, right (R): 64 cm/s, coefficient of variation (CV) 11%], response amplitude (L: 16, R: 13 cm/s, CV 23%), TD (L: 54, R: 52 s, CV 9%), (L: 30, R: 30 s, CV 22%), and mean response time (MRT) (L: 83, R: 82 s, CV 8%) between left and right MCAV as supported by the high correlations (e.g., MRT r = 0.82, P < 0.05) and low CVs. Test-retest reliability was high with CVs for the baseline, amplitude, and MRT of 3, 14, and 12%, respectively. These responses contrasted markedly with those of three healthy older subjects in whom the MCAV baseline and exercise response amplitude were far lower and the kinetics slowed. A single older stroke patient showed baseline ipsilateral MCAV that was lower still and devoid of any exercise response whatsoever. We conclude that kinetics analysis of MCAV during exercise has significant potential to unveil novel aspects of cerebrovascular function in health and disease.
NEW & NOTEWORTHY Resolution of the dynamic stimulus-response profile provides a greater understanding of the underlying the physiological control processes than steady-state measurements alone. We report a novel method of measuring cerebrovascular blood velocity (MCAv) kinetics under ecologically valid conditions from rest to moderate-intensity exercise. This technique reveals that brain blood flow increases exponentially following the onset of exercise with 1) a strong bilateral coherence in young healthy individuals, and 2) a potential for unique age- and disease-specific profiles.
Genetic architectures of plant height, stem thickness, spike length, awn length, heading date, thousand-kernel weight, kernel length, leaf area and chlorophyll content were aligned on the DArT-based high-density map of the 541 × Ot1–3 RILs population of rye using the genes interaction assorting by divergent selection (GIABDS) method. Complex sets of QTL for particular traits contained 1–5 loci of the epistatic D class and 10–28 loci of the hypostatic, mostly R and E classes controlling traits variation through D–E or D–R types of two-loci interactions. QTL were distributed on each of the seven rye chromosomes in unique positions or as a coinciding loci for 2–8 traits. Detection of considerable numbers of the reversed (D′, E′ and R′) classes of QTL might be attributed to the transgression effects observed for most of the studied traits. First examples of E* and F QTL classes, defined in the model, are reported for awn length, leaf area, thousand-kernel weight and kernel length. The results of this study extend experimental data to 11 quantitative traits (together with pre-harvest sprouting and alpha-amylase activity) for which genetic architectures fit the model of mechanism underlying alleles distribution within tails of bi-parental populations. They are also a valuable starting point for map-based search of genes underlying detected QTL and for planning advanced marker-assisted multi-trait breeding strategies.
Ca2+ influx via the L-type Ca2+ channel Cav1.2 triggers our heartbeat. Perinatally and particularly at birth, angiotensin II is produced to augment necessary physiological changes in blood flow such as pulmonary perfusion.
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The earliest vertebrates were agnathans—fish-like organisms without jaws, which first appeared near the end of the Cambrian radiation. One group of agnathans became cyclostomes, which include lamprey and hagfish. Other agnathans gave rise to jawed vertebrates or gnathostomes, the group including all other existing vertebrate species. Because cyclostomes diverged from other vertebrates 500 million years ago, it may be possible to infer some of the properties of the retina of early vertebrate progenitors by comparing lamprey to other vertebrates. We have previously shown that rods and cones in lamprey respond to light much like photoreceptors in other vertebrates and have a similar sensitivity. We now show that these affinities are even closer. Both rods and cones adapt to background light and to bleaches in a manner almost identical to other vertebrate photoreceptors. The operating range in darkness is nearly the same in lamprey and in amphibian or mammalian rods and cones; moreover background light shifts response-intensity curves downward and to the right over a similar range of ambient intensities. Rods show increment saturation at about the same intensity as mammalian rods, and cones never saturate. Bleaches decrease sensitivity in part by loss of quantum catch and in part by opsin activation of transduction. These correspondences are so numerous and pervasive that they are unlikely to result from convergent evolution but argue instead that early vertebrate progenitors of both cyclostomes and mammals had photoreceptors much like our own.
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Extracellular matrix (ECM) stiffening is a key element of cardiac disease. Increased rigidity of the ECM passively inhibits cardiac contraction, but if and how matrix stiffening also actively alters cardiomyocyte contractility is incompletely understood. In vitro models designed to study cardiomyocyte-matrix interaction lack the possibility to separate passive inhibition by a stiff matrix from active matrix-induced alterations of cardiomyocyte properties. Here we introduce a novel experimental model that allows exploration of cardiomyocyte functional alterations in response to matrix stiffening. Adult rat cardiomyocytes were cultured for 24 hours on matrices of tuneable stiffness representing the healthy and the diseased heart and detached from their matrix before functional measurements. We demonstrate that matrix stiffening, independent of passive inhibition, reduces cell shortening and Ca2+ handling but does not alter myofilament generated force. Additionally, detachment of adult cultured cardiomyocytes allowed the transfer of cells from one matrix to another. This revealed that stiffness-induced cardiomyocyte changes are reversed when matrix stiffness is normalised. These matrix stiffness-induced changes in cardiomyocyte function could not be explained by adaptation in the microtubules. Additionally, cardiomyocytes isolated from stiff hearts of the obese ZSF1 rat-model of heart failure with preserved ejection fraction, show more pronounced reduction in unloaded shortening in response to matrix stiffening. Taken together, we introduce a method that allows evaluation of the influence of ECM properties on cardiomyocyte function apart from the passive inhibitory component of a stiff matrix. As such, it adds an important and physiological relevant tool to investigate the functional consequences of cardiomyocyte-matrix interactions.
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