The nonsense mutation stop+4 model correlates with motor changes in Duchenne muscular dystrophy

The aim was to assess 3-year longitudinal data using 6MWT in 26 ambulant boys affected by DMD carrying nonsense mutations and to compare their results to other small mutations. We also wished to establish, within the nonsense mutations group, patterns of change according to several variables. Patients with nonsense mutations were categorized according to the stop codon type newly created by the mutation and also including the adjacent 5′ (upstream) and 3′ (downstream) nucleotides. No significant difference was found between nonsense mutations and other small mutations (p > 0.05) on the 6MWT. Within the nonsense mutations group, there was no difference in 6MWT when the patients were subdivided according to: Type of stop codon, frame status of exons involved, protein domain affected. In contrast, there was a difference when the stop codon together with the 3′ adjacent nucleotide (“stop+4 model”) was considered (p < 0.05) with patients with stop codon TGA and 3′ adjacent nucleotide G (TGAG) having a more rapid decline. Our finding suggest that the stop+4 model may help in predicting functional changes. This data will be useful at the time of interpreting the long term follow up of patients treated with Ataluren that are becoming increasingly available.     

Circulating prostaglandin E2: a novel potential prognostic biomarker in patients with hepatocellular carcinoma

Clinical and Experimental Medicine - We aimed to explore the activation of monoacylglycerol lipase (MAGL)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) axis in hepatocellular carcinoma (HCC),...     

A Paradigm Shift for Torsional Stiffness of Nickel-Titanium Rotary Instruments: A Finite Element Analysis

IntroductionThe aim of this study was to investigate the influence of mass and the polar moment of inertia on the torsional behavior of nickel-titanium rotary instruments to understand which parameter of cross-sectional design had a key role in terms of torsional resistance.MethodsFour different instrument models were designed and meshed using computer-aided engineering software (SolidWorks; Dassault Systems, Waltham, MA). Instrument models shared the same characteristics, except for cross-sectional design; triangle, rectangle, square, and hollow square geometry was selected. Finite element analysis was performed simulating a static torsional test using the FEEPlus internal solver (Solid Works). Von Mises stress and torsional load at fracture were calculated by the software. Linear regression analysis was performed to investigate the relationship of the polar moment of inertia, cross-sectional area, inner core radius, and mass per volume on the torsional resistance of nickel-titanium rotary instruments.ResultsThe polar moment of inertia positively affected the maximum torsional load with the highest level of correlation (R² = 0.917). It could be stated that the higher the polar moment of inertia is, the more maximum torsional load at fracture is present. Mass and cross-sectional area had a lower level of correlation compared with the polar moment of inertia (R² = 0.5533). According to this, 2 instruments with the same mass/mm and/or cross-sectional area could have different torsional resistance.ConclusionsThe polar moment of inertia can be considered as the most important cross-sectional factor in determining the torsional resistance of rotary instruments over metal mass and cross-sectional area.     

Influence of shaft length on torsional behavior of endodontic nickel–titanium instruments

Odontology - Torsional stresses are one of the most frequent causes of intracanal separation of nickel–titanium endodontic instruments, which represents a great concern of endodontists. For...     

Motion in the Unstable Cervical Spine When Transferring a Patient Positioned Prone to a Spine Board

Context:

Two methods have been proposed to transfer an individual in the prone position to a spine board. Researchers do not know which method provides the best immobilization.

Objective:

To determine if motion produced in the unstable cervical spine differs between 2 prone logrolling techniques and to evaluate the effect of equipment on the motion produced during prone logrolling.

Design:

Crossover study.

Setting:

Laboratory.

Patients or Other Participants:

Tests were performed on 5 fresh cadavers (3 men, 2 women; age = 83 ± 8 years, mass = 61.2 ± 14.1 kg).

Main Outcome Measure(s):

Three-dimensional motions were recorded during 2 prone logroll protocols (pull, push) in cadavers with an unstable cervical spine. Three equipment conditions were evaluated: football shoulder pads and helmet, rigid cervical collar, and no equipment. The mean range of motion was calculated for each test condition.

Results:

The pull technique produced 16% more motion than the push technique in the lateral-bending angulation direction (F_1,4 = 19.922, P = .01, η² = 0.833). Whereas the collar-only condition and, to a lesser extent, the football-shoulder-pads-and-helmet condition demonstrated trends toward providing more stability than the no-equipment condition, we found no differences among equipment conditions. We noted an interaction between technique and equipment, with the pull maneuver performed without equipment producing more anteroposterior motion than the push maneuver in any of the equipment conditions.

Conclusions:

We saw a slight difference in the motion measured during the 2 prone logrolling techniques tested, with less lateral-bending and anteroposterior motion produced with the logroll push than the pull technique. Therefore, we recommend adopting the push technique as the preferred spine-boarding maneuver when a patient is found in the prone position. Researchers should continue to seek improved methods for performing prone spine-board transfers to further decrease the motion produced in the unstable spine.Key Words: injuries, transfer techniques, logroll

Key Points

• A slight difference in motion was measured between the 2 prone logrolling techniques, with the push technique producing less lateral-bending and anterior-posterior motion than the pull technique.
• The logroll push technique should be adopted as the preferred spine-boarding maneuver when a patient is found in the prone position.
• Individuals who may need to perform this rescue procedure should practice and become proficient in the logroll push technique.
• Researchers should continue to seek improved methods for transferring patients positioned prone to spine boards to further reduce the motion transmitted to the unstable spine.

Each year, 12 000 incidents of nonfatal spinal cord injury are reported in the United States.¹ Approximately 8.0% of these injuries occur during sport participation.¹ Of all US sports, American football has by far the greatest number of spinal injuries. Between 1982 and 2007, the incidence of direct injuries in males playing American football was 1.89 per 100 000 participants in a college setting and 0.75 per 100 000 participants in a high school setting.²The prehospital management of spinal cord injuries is critical to prevent exacerbation of the injury. In 3% to 25% of patients, neurologic deterioration occurs during the initial management of spinal cord injuries.³ During immobilization and transportation of the patient to the hospital, precautions must be taken to transmit as little motion as possible to the spine. One of the first transfers that rescuers must perform is placing the injured athlete onto a long, rigid spine board. When the injured athlete is supine, lift-and-slide spine-board transfers produce less motion in the spine than logroll spine-board transfers.^4–6 However, when the patient is found in the prone position, a lift-and-slide transfer cannot be performed successfully, and a logroll technique must be used.Swartz et al⁷ recommended how to best manage a catastrophic spine injury in the athlete. They described 2 techniques for logrolling an athlete who is positioned prone: the prone logroll push and the prone logroll pull. Researchers⁸ have shown that the logroll push produces less motion in the unstable thoracolumbar spine. No one knows which of the prone spine-boarding techniques provides the best immobilization in the unstable cervical spine. Therefore, the primary purpose of our study was to determine if motion produced in the unstable cervical spine differs between 2 prone logrolling techniques. Our null hypothesis was that no difference would exist in the amount of motion allowed between the 2 prone logrolling techniques. Our secondary purpose was to evaluate the effect of equipment on the motion produced during the prone logrolling technique. Our null hypothesis was that no difference would exist in the amount of motion allowed among any of the equipment conditions.     

Profiling celiac disease antibody repertoire

The aim of this study was to dissect the autoantibody response in celiac disease (CD) that remains largely unknown, with the goal of identifying the disease-specific autoantigenic protein pattern or the so called epitome. Sera from CD patients were used to select immunoreactive antigens from a cDNA phage-display library. Candidate genes were identified, the corresponding proteins produced and their immunoreactivity validated with sera from CD patients and controls. Thirteen CD-specific antigens were identified and further validated by protein microarray. The specificity for 6 of these antigens was confirmed by ELISA. Furthermore we showed that this antibody response was not abolished on a gluten free diet and was not shared with other autoimmune diseases. These antigens appear to be CD specific and independent of gluten induction. The utility of this panel extends beyond its diagnostic value and it may drive the attention to new targets for unbiased screens in autoimmunity research.     

Thalamo-cortical networks in subtypes of migraine with aura patients

BackgroundWe searched for differences in resting-state functional connectivity (FC) between brain networks and its relationship with the microstructure of the thalamus between migraine with pure visual auras (MA), and migraine with complex neurological auras (MA+), i.e. with the addition of at least one of sensory or language symptom.Methods3T MRI data were obtained from 20 patients with MA and 15 with MA + and compared with those from 19 healthy controls (HCs). We collected resting state data among independent component networks. Diffusivity metrics of bilateral thalami were calculated and correlated with resting state ICs-Z-scores.ResultsAs compared to HCs, both patients with MA and MA + disclosed disrupted FC between the default mode network (DMN) and the right dorsal attention system (DAS). The MA + subgroup had lower microstructural metrics than both HCs and the MA subgroup, which correlated negatively with the strength of DMN connectivity. Although the microstructural metrics of MA patients did not differ from those of HCs, these patients lacked the correlation with the strength of DAS connectivity found in HCs.ConclusionsThe present findings suggest that, as far as MRI profiles are concerned, the two clinical phenotypes of migraine with aura have both common and distinct morpho-functional features of nodes in the thalamo-cortical network.