Abstract
Aims
Metabolic cardiomyopathy (MC)—characterized by intra-myocardial triglyceride (TG) accumulation and lipotoxic damage—is an emerging cause of heart failure in obese patients. Yet, its ...mechanisms remain poorly understood. The Activator Protein 1 (AP-1) member JunD was recently identified as a key modulator of hepatic lipid metabolism in obese mice. The present study investigates the role of JunD in obesity-induced MC.
Methods and results
JunD transcriptional activity was increased in hearts from diet-induced obese (DIO) mice and was associated with myocardial TG accumulation and left ventricular (LV) dysfunction. Obese mice lacking JunD were protected against MC. In DIO hearts, JunD directly binds PPARγ promoter thus enabling transcription of genes involved in TG synthesis, uptake, hydrolysis, and storage (i.e. Fas, Cd36, Lpl, Plin5). Cardiac-specific overexpression of JunD in lean mice led to PPARγ activation, cardiac steatosis, and dysfunction, thereby mimicking the MC phenotype. In DIO hearts as well as in neonatal rat ventricular myocytes exposed to palmitic acid, Ago2 immunoprecipitation, and luciferase assays revealed JunD as a direct target of miR-494-3p. Indeed, miR-494-3p was down-regulated in hearts from obese mice, while its overexpression prevented lipotoxic damage by suppressing JunD/PPARγ signalling. JunD and miR-494-3p were also dysregulated in myocardial specimens from obese patients as compared with non-obese controls, and correlated with myocardial TG content, expression of PPARγ-dependent genes, and echocardiographic indices of LV dysfunction.
Conclusion
miR-494-3p/JunD is a novel molecular axis involved in obesity-related MC. These results pave the way for approaches to prevent or treat LV dysfunction in obese patients.
Determination of auditory function is a fundamental part of a complete neurologic examination. Disability from permanent hearing loss is common in the general population. Current bedside auditory ...tests are unreliable and cumbersome. We evaluated the calibrated finger rub auditory screening test (CALFRAST) as a routine diagnostic tool.
The sound spectrum and mean peak intensities of standard finger rub were measured, as well as background noise. CALFRAST overlapped the frequency spectrum of normal speech. Patients and companions were recruited from a neurology clinic. With arms extended, two stimulus intensities were presented: strong finger rub (CALFRAST-Strong 70) and the faintest rub that the examiner could hear (CALFRAST-Faint 70). With subjects' eyes closed, each ear's CALFRAST threshold was ascertained and then compared with its audiometric measure. The normal threshold was considered to be 25 dB. Validity, reliability, and discrimination abilities were obtained using standard methods.
Two hundred twenty-one subjects (442 ears; 58% women) were examined. Ages ranged from 18 to 88 years, with a mean of 46 years. Eighty-five subjects (39%) had some degree of hearing loss. Both specificity and positive predictive value of CALFRAST-Strong 70 were 100%. Both sensitivity and negative predictive value of CALFRAST-Faint 70 were 99%, with a negative likelihood ratio <0.1. Area under the receiver operating characteristic curve was 0.94, consistent with excellent discrimination ability. Both intrarater and interrater reliability were excellent, both kappa >0.8. Subjects' self-assessment of hearing was unreliable.
The calibrated finger rub auditory screening test (CALFRAST) is simple, accurate, inexpensive, and reliable. As a routine screening tool, CALFRAST may contribute to more efficient identification of auditory impairment.
Using a cadaveric 3-part fracture model and cyclic loading protocol, our study objectives were to quantify the stabilizing effect of tension-reducing rotator cuff sutures in terms of fracture ...displacement across the surgical neck and greater tuberosity compared with a control group in which no sutures were used.
Six matched pairs of fresh frozen specimens underwent a standardized, 3-part, proximal humerus fracture and were split into 2 groups. The control group had the fracture fixed with a plate and screw construct only while the experimental group had additional suture fixation through the plate to each rotator cuff tendon. Active abduction through the rotator cuff was simulated for 100, 200, 300, and 400 cycles and to failure at 1000 N. A Mann-Whitney U test compared cyclic displacement of the greater tuberosity and surgical neck fracture gaps and load to failure between the 2 groups.
There was no significant difference (P > 0.05) in fracture gap between fixation methods at the surgical neck at 100 (P = 0.13), 200 (P = 0.07), 300 (P = 0.49), and 400 (P = 0.07) cycles. There was no significant difference (P > 0.05) between fixation methods in the fracture gap at the greater tuberosity at 100 (P = 0.39), 200 (P = 1.00), 300 (P = 0.31), and 400 (P = 0.59) cycles. There was no significant difference (P > 0.5) at 1000 N at the surgical neck (P = 0.70) or the greater tuberosity (P = 0.39).
Tension-relieving rotator cuff sutures do not add stability to the repair of 3-part proximal humerus fractures. Varus collapse and greater tuberosity displacement are common complications associated with 3-part fractures. No mechanical data exist to demonstrate benefit of adding suture to a plate and screw construct for limiting fracture displacement.
In this contribution, Fe3O4 magnetic nanoparticles (MNPs) have been functionalized with a tetraphosphonate cavitand receptor (Tiiii), capable of complexing N-monomethylated species with high ...selectivity, and polyethylene glycol (PEG) via click-chemistry. The grafting process is based on MNP pre-functionalization with a bifunctional phosphonic linker, 10-undecynylphosphonic acid, anchored on an iron surface through the phosphonic group. The Tiiii cavitand and the PEG modified with azide moieties have then been bonded to the resulting alkyne-functionalized MNPs through a "click" reaction. Each reaction step has been monitored by using X-ray photoelectron and FTIR spectroscopies. PEG and Tiiii functionalized MNPs have been able to load N-methyl ammonium salts such as the antitumor drug procarbazine hydrochloride and the neurotransmitter epinephrine hydrochloride and release them as free bases. In addition, the introduction of PEG moieties promoted biocompatibility of functionalized MNPs, thus allowing their use in biological environments.
E-health applications can support continuing care for persons with chronic diseases such as multiple sclerosis (MS). We have developed a web-based mobile app called VIOLA to be used at home by ...persons with MS (pwMS) who previously participated in an innovative multidisciplinary rehab program. The purpose of VIOLA is to reinforce what participants have learned about a healthy lifestyle and to keep them motivated to adhere to rehabilitation programs. As the outbreak of the Covid-19 pandemic has severely curtailed pwMS contact with their usual health providers, we quickly updated VIOLA to grant continuity of care to our home-bound patients.
By monitoring pwMS subscriptions to individual modules, we found a definite increase after the national lockdown was declared. Subscribers rated the app very positively.
Encouraged by the positive feedbacks, we are planning to extend the access to our app also to pwMS with no prior specific learning experience. This would limit the psychophysical consequences of the lockdown. Furthermore, VIOLA could be effective in maintaining a proper lifestyle, contributing to improve the quality of life of pwMS.
VIOLA has the potential of increasing the adherence of pwMS to the rehabilitation confirming that digital communication tools are a valuable solution for those home-bound.
The purpose of the study was to trace the development of listening and reading comprehension over the period of a year. The study entailed administering Sentence Verification Technique (SVT) tests to ...151 third- and fourth-grade students on three occasions (in May at the end of the school year, in September of the next school year, and in May of the same school year). An analysis of variance revealed a significant modality of test by time of test administration interaction. The nature of this interaction was that listening comprehension performance showed relatively steady gains across the three test occasions while reading comprehension performance showed no significant gain on the second administration after a summer, but did show significant gains on the third administration, after a school year. The results are interpreted as indicating that reading and listening comprehension can be measured with SVT tests and that the two comprehension modalities develop independently with reading comprehension being more sensitive to instruction.
In the reported study, we tested the hypothesis that the comprehension of reading material drawn from a college course could be used to predict learning performance in that course. Students enrolled ...in an educational psychology course or a business statistics course took at the beginning of the semester comprehension tests that were based on both psychology and statistics texts. The reading comprehension scores were related to examination performance in the courses and to overall college grade point average (GPA). For comparison purposes, Scholastic Aptitude Test scores were related to the same variables. The results revealed that course-relevant reading comprehension performance (i.e., psychology in the psychology course, statistics in the statistics course) was a significant predictor of course performance but not of GPA. The results are discussed in terms of a model of comprehension that contains general and specific factors.
Varus failure is a well-known complication of open reduction internal fixation of proximal humeral fractures. The addition of tension-reducing sutures from the plate to the rotator cuff may attenuate ...the deforming forces of the rotator cuff resulting in decreased varus failure. In this study, we investigate the biomechanical contributions of tension-reducing sutures to a locked plate construct in a 2-part proximal humerus fracture model.
Two fixation techniques were tested in 12 matched fresh frozen humeri in which standard 2-part fractures of the surgical neck were created with a gap simulating surgical neck medial comminution. In group 1, fractures were fixed with a standard proximal humerus locking plate. In group 2, the plate fixation was similar, and additionally, tension-reducing sutures were applied from the plate to the rotator cuff. Active abduction was simulated for 400 cycles with force applied through the rotator cuff tendons. Intercyclic fracture motion, change in displacement, and load to failure were recorded.
The addition of tension-reducing sutures did not lead to significant differences in intercyclic fracture motion. The mean change in displacement and load to failure were similar in both groups. Failure typically occurred in both groups at the rotator cuff testing clamp interface.
Tension-relieving rotator cuff sutures added to locking plate fixation did not lead to a change in fracture gap with cyclic loading or an increase in ultimate failure load in a 2-part surgical neck proximal humerus fracture model without medial support.
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