Interference with Ca2+ release activated Ca2+ (CRAC) channel function delays T‐cell arrest in vivo

Entry of lymphocytes into secondary lymphoid organs (SLOs) involves intravascular arrest and intracellular calcium ion ([Ca²⁺]_i) elevation. TCR activation triggers increased [Ca²⁺]_i and can arrest T‐cell motility in vitro. However, the requirement for [Ca²⁺]_i elevation in arresting T cells in vivo has not been tested. Here, we have manipulated the Ca²⁺ release‐activated Ca²⁺ (CRAC) channel pathway required for [Ca²⁺]_i elevation in T cells through genetic deletion of stromal interaction molecule (STIM) 1 or by expression of a dominant‐negative ORAI1 channel subunit (ORAI1‐DN). Interestingly, the absence of CRAC did not interfere with homing of naïve CD4⁺ T cells to SLOs and only moderately reduced crawling speeds in vivo. T cells expressing ORAI1‐DN lacked TCR activation induced [Ca²⁺]_i elevation, yet arrested motility similar to control T cells in vitro. In contrast, antigen‐specific ORAI1‐DN T cells had a twofold delayed onset of arrest following injection of OVA peptide in vivo. CRAC channel function is not required for homing to SLOs, but enhances spatiotemporal coordination of TCR signaling and motility arrest.     

A phonetic radical account of the phonology-to-Orthography consistency effect on writing Chinese characters: Evidence from a Chinese Dysgraphic patient

ABSTRACT

This study investigated the sublexical route in writing Chinese characters. Using a writing-to-dictation task, we compared neurotypical participants’ performance on writing a set of 40 characters with homophones sharing different phonetic radicals and another set of 40 characters with homophones sharing the same phonetic radicals. The first set of stimuli was regarded as both syllable-to-character and syllable-to-radical inconsistent, while the second set of stimuli was considered syllable-to-radical consistent but syllable-to-character inconsistent. The results of the error analysis showed that the control participants demonstrated a greater tendency to make errors with preserved phonetic radicals in the second set of stimuli. Furthermore, we conducted the same task with a Chinese brain-injured patient, WCY, who had mild dyslexia and severe dysgraphia associated with mild impairment to the lexical semantic route as shown by the patient’s character writing. The results showed that WCY demonstrated similar error patterns as those of the control participants and a shorter writing time in the second set of stimuli. Altogether, the observations were taken as evidence that supported our claim that a syllable-to-phonetic radical route governs the sublexical route in Chinese character writing.     

2020 SCCT Guideline for Training Cardiology and Radiology Trainees as Independent Practitioners (Level II) and Advanced Practitioners (Level III) in Cardiovascular Computed Tomography: A Statement from the Society of Cardiovascular Computed Tomography

Cardiovascular computed tomography (CCT) is a well-validated non-invasive imaging tool with an ever-expanding array of applications beyond the assessment of coronary artery disease. These include the evaluation of structural heart diseases, congenital heart diseases, peri-procedural electrophysiology applications, and the functional evaluation of ischemia. This breadth requires a robust and diverse training curriculum to ensure graduates of CCT training programs meet minimum competency standards for independent CCT interpretation. This statement from the Society of Cardiovascular Computed Tomography aims to supplement existing societal training guidelines by providing a curriculum and competency framework to inform the development of a comprehensive, integrated training experience for cardiology and radiology trainees in CCT.     

Abusive head trauma in court: a multi-center study on criminal proceedings in Germany

International Journal of Legal Medicine - The shaken baby syndrome (SBS) is a common variant of abusive head trauma (AHT) in infants and toddlers. Data on the legal outcome of such cases are still...     

Comparing downstream consequences of normal exercise stress echocardiograms and cardiac computed tomography angiography scans in patients suspected of having of obstructive coronary artery disease: a retrospective cohort study of Tricare beneficiaries

The International Journal of Cardiovascular Imaging - To compare overall number of downstream tests and total costs between negative exercise stress echocardiograms (ESE) or cardiac computed...     

Risk factors for complications and readmission after operative fixation of pediatric femur fractures

Purpose

Operative fixation of pediatric femur fractures with intramedullary implants has grown in popularity in recent decades. However, risk factors for short-term adverse events and readmission have not been well studied.

Methods

Pediatric patients who underwent intramedullary nailing of a femur fracture between 2012 and 2013 were identified from the American College of Surgeons National Surgical Quality Improvement Program database. Risk factors for any adverse event (AAE) and readmission after intramedullary nailing were evaluated using univariate and multivariate analysis.

Results

A total of 522 pediatric patients who underwent intramedullary nailing of the femur during the study period were identified. The mean age of this patient cohort was 10.2 ± 3.8 years. Review of the cases revealed that 18 (3.4 %) patients had AAE and that 20 (3.8 %) patients were readmitted, of whom 13 (2.5 %) underwent a reoperation. Independent risk factors for AAE were a cardiac comorbidity [odds ratio (OR) 12.7, 95 % confidence interval (CI) 1.5, 103.7], open fracture (OR 10.2, 95 % CI 1.4, 74.4), and prolonged operative time (OR 17.5, 95 % CI 6.1, 50.5). Independent risk factors for readmission were a central nervous system disorder (OR 4.5, 95 % CI 1.3, 16.2) and a seizure disorder (OR 4.9, 95 % CI 1.0, 23.5).

Conclusions

The results of the multivariate analysis suggest that cardiac comorbidities, open fractures, and prolonged operative time increase the risk for AAE and that central nervous system disorders and seizure disorders may increase the risk for readmission. Surgeons should be aware of these risk factors and counsel the families of pediatric patients who undergo intramedullary nailing of femur fractures.     

Discrimination of MHC-derived odors by untrained mice is consistent with divergence in peptide-binding region residues

Genes of the major histocompatibility complex (MHC) play a central role in immune recognition, yet they also influence the odor of individuals. Mice can be trained to distinguish odors mediated by classical MHC loci; however, training can introduce confounding behavioral artifacts. This study demonstrates that mice can distinguish some, but not all, naturally occurring allelic variants at classical MHC loci without prior training. This result suggests that MHC-disassortative mating preferences might operate by means of small MHC-based odor differences, and could therefore contribute to diversifying selection acting on MHC loci. Here we show that odors of two MHC mutant mouse strains (bm1 and bm3) can be distinguished, even after genetic background is controlled by intercrossing strains. These two strains differ by five amino acids, three of which are predicted to chemically contact peptides bound to the peptide-binding region (PBR), the site of antigen presentation for T cell recognition. However, the odors of neither bm1 nor bm3 were distinguished from their parental B6 haplotype after randomizing genomic background, despite discrimination of pure-bred B6 and bm1 strain odors. These combined results suggest that (i) there may be an MHC odor discrimination threshold based on divergence in PBR residues, providing a more logical pattern of MHC-based odor discrimination than found in previous training studies, where discrimination ability was not correlated with PBR divergence; and (ii) additional (non-MHC) mutations that influence odor have accumulated in these strains during the 100 generations of divergence between pure B6 and bm1 strains.     

Cervical Spine Motion During Football Equipment-Removal Protocols: A Challenge to the All-or-Nothing Endeavor

Context

The National Athletic Trainers'' Association position statement on acute management of the cervical spine-injured athlete recommended the all-or-nothing endeavor, which involves removing or not removing both helmet and shoulder pads, from equipment-laden American football and ice hockey athletes. However, in supporting research, investigators have not considered alternative protocols.

Objective

To measure cervical spine movement (head relative to sternum) produced when certified athletic trainers (ATs) use the all-or-nothing endeavor and to compare these findings with the movement produced using an alternative pack-and-fill protocol, which involves packing the area under and around the cervical neck and head with rolled towels.

Design

Crossover study.

Setting

Movement analysis laboratory.

Patients or Other Participants

Eight male collegiate football players (age = 21.4 ± 1.4 years; height = 1.87 ± 0.02 m; mass = 103.6 ± 12.5 kg).

Intervention(s)

Four ATs removed equipment under 4 conditions: removal of helmet only followed by placing the head on the ground (H), removal of the helmet only followed by pack-and-fill (HP), removal of the helmet and shoulder pads followed by placing the head on the ground (HS), and removal of the helmet and shoulder pads followed by pack-and-fill (HSP). Motion capture was used to track the movement of the head with respect to the sternum during equipment removal.

Main Outcome Measure(s)

We measured head movement relative to sternum movement (translations and rotations). We used 4 × 4 analyses of variance with repeated measures to compare discrete motion variables (changes in position and total excursions) among protocols and ATs.

Results

Protocol HP resulted in a 0.1 ± 0.6 cm rise in head position compared with a 1.4 ± 0.3 cm drop with protocol HS (P < .001). Protocol HP produced 4.9° less total angular excursion (P < .001) and 2.1 cm less total vertical excursion (P < .001) than protocol HS.

Conclusions

The pack-and-fill protocol was more effective than shoulder pad removal in minimizing cervical spine movement throughout the equipment-removal process. This study provides evidence for including the pack-and-fill protocol in future treatment recommendations when helmet removal is necessary for on-field care.Key Words: National Athletic Trainers'' Association position statement, pack and fill, motion analysis, helmet removal

Key Points

• The pack-and-fill protocol resulted in less overall motion than removal of the helmet and shoulder pads followed by placing the head on the ground, which is currently endorsed by the National Athletic Trainers'' Association.
• Using pack and fill, the athletic trainers could position the head at release in, on average, nearly the identical position as at initiation.
• Removal of the helmet and shoulder pads resulted in a drop in linear and angular head position, placing the cervical spine into increased extension.

American football has the highest number of catastrophic cervical spine injuries of all sports in the United States.¹ Although still of major concern, the incidence of catastrophic cervical spine injuries has declined over the past 35 years, and the rate is now less than 1 per 100 000 exposures.² Much of this decline has been attributed to a 1976 rule change making it illegal to spear, or lower the head to butt or ram an opponent.² Given the force applied at the front and top of a player''s helmet, spearing has long been associated with the axial-load mechanism of injury that results in catastrophic cervical spine injury.³ However, despite a focus on player safety, researchers^4–6 have suggested that the incidence of spearing or other axial head impacts may be as prevalent in American football in the United States today as before the 1976 rule change. Instead, improved prehospital care and on-field management of equipment-laden athletes with potential spine injuries possibly also has led to a reduction in catastrophic cervical spine injuries by reducing the number of cervical spine injuries that result in catastrophic outcomes. This possibility needs to be documented, and research pertaining to prehospital care protocols and management techniques that may affect catastrophic spinal cord injury outcomes in American football needs to continue.Proper prehospital on-field medical care of the athlete with a spine injury, including equipment management, may be critical in limiting secondary cervical spine injury while also allowing access to the airway and chest compressions. The National Athletic Trainers'' Association (NATA) position statement on the acute management of the cervical spine-injured athlete⁷ includes the all-or–nothing technique, which discourages independent removal of the helmet or shoulder pads in American football or ice hockey when an athlete has a potential cervical spine injury. This specific NATA recommendation is based on several studies^8–11 in which the researchers measured vertebral positioning or spinal cord space before and after equipment removal and showed that when the football helmet is removed while the shoulder pads remain in place, cervical alignment can be compromised as the head and neck fall backward into extension.However, a gap exists in the body of evidence used to support this recommendation, as no authors of supporting studies have addressed the use of fillers (eg, rolled towels) to stabilize the head and cervical spine after removing only the helmet and leaving the shoulder pads on the athlete. This technique, termed pack and fill, would fill the void of the missing helmet by placing rolled towels around and beneath the posterior head, cervical spine, and surface of the spine board or ground to prevent the head and cervical spine from moving into extension during performance of critical-care tasks. Although the NATA position statement⁷ mentions this technique as a possibility for an athlete whose helmet is dislodged or shoulder pads are not removed easily, pack and fill could be an alternative clinical practice when removal of the helmet is necessary to provide safe access to the airway (eg, inability to remove the facemask efficiently or a poorly fitted football helmet creating instability of the head and cervical spine within the helmet). Decoster et al¹² recently demonstrated that pack and fill can effectively maintain a neutral sagittal cervical alignment after helmet removal.Another gap in these supporting studies is that they were based on static imaging and, therefore, did not account for the amount of head and neck movement that occurs during the equipment-removal process. In the case of shoulder-pad removal, this could be substantial. Therefore, the purposes of our study were to address these 2 gaps by measuring cervical spine movement (head with respect to sternum) throughout the removal process and to compare this movement among several possible removal protocols. We hypothesized that removal of the helmet combined with the pack-and-fill technique would result in less overall movement than removal of both the helmet and shoulder pads.     

Independent effects of circulating glucose,insulin and NEFA on cardiac triacylglycerol accumulation and myocardial insulin resistance in a swine model

Aims/hypothesis

Cardiac steatosis and myocardial insulin resistance elevate the risk of cardiac complications in obesity and diabetes. We aimed to disentangle the effects of circulating glucose, insulin and NEFA on myocardial triacylglycerol (TG) content and myocardial glucose uptake.

Methods

Twenty-two pigs were stratified according to four protocols: low NEFA?+?low insulin (nicotinic acid), high NEFA?+?low insulin (fasting) and high insulin?+?low NEFA?±?high glucose (hyperinsulinaemia–hyperglycaemia or hyperinsulinaemia–euglycaemia). Positron emission tomography, [U-¹³C]palmitate enrichment techniques and tissue biopsies were used to assess myocardial metabolism. Heart rate and rate–pressure product (RPP) were monitored.

Results

Myocardial glucose extraction was increased by NEFA suppression and was similar in the hyperinsulinaemia–hypergylcaemia, hyperinsulinaemia–euglycaemia and nicotinic acid groups. Hyperglycaemia enhanced myocardial glucose uptake due to a mass action. Myocardial TG content was greatest in the fasting group, whereas hyperinsulinaemia had a mild effect. Heart rate and RPP increased in hyperinsulinaemia–euglycaemia, in which cardiac glycogen content was reduced. Heart rate correlated with myocardial TG and glycogen content.

Conclusions/interpretation

Elevated NEFA levels represent a powerful, self-sufficient promoter of cardiac TG accumulation and are a downregulator of myocardial glucose uptake, indicating that the focus of treatment should be to ‘normalise’ adipose tissue function to lower the risk of cardiac TG accumulation and myocardial insulin resistance. The observation that hyperinsulinaemia and nicotinic acid led to myocardial fuel deprivation provides a potential explanation for the cardiovascular outcomes reported in recent intensive glucose-lowering and NEFA-lowering clinical trials.