Whole exome sequencing reveals de novo pathogenic variants in KAT6A as a cause of a neurodevelopmental disorder

Neurodevelopmental disorders (NDD) are common, with 1–3% of general population being affected, but the etiology is unknown in most individuals. Clinical whole-exome sequencing (WES) has proven to be a powerful tool for the identification of pathogenic variants leading to Mendelian disorders, among which NDD represent a significant percentage. Performing WES with a trio-approach has proven to be extremely effective in identifying de novo pathogenic variants as a common cause of NDD. Here we report six unrelated individuals with a common phenotype consisting of NDD with severe speech delay, hypotonia, and facial dysmorphism. These patients underwent WES with a trio approach and de novo heterozygous predicted pathogenic novel variants in the KAT6A gene were identified. The KAT6A gene encodes a histone acetyltransfrease protein and it has long been known for its structural involvement in acute myeloid leukemia; however, it has not previously been associated with any congenital disorder. In animal models the KAT6A ortholog is involved in transcriptional regulation during development. Given the similar findings in animal models and our patient's phenotypes, we hypothesize that KAT6A could play a role in development of the brain, face, and heart in humans. © 2016 Wiley Periodicals, Inc.

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Syndrome disintegration: Exome sequencing reveals that Fitzsimmons syndrome is a co-occurrence of multiple events

In 1987 Fitzsimmons and Guilbert described identical male twins with progressive spastic paraplegia, brachydactyly with cone shaped epiphyses, short stature, dysarthria, and "low-normal" intelligence. In subsequent years, four other patients, including one set of female identical twins, a single female child, and a single male individual were described with the same features, and the eponym Fitzsimmons syndrome was adopted (OMIM #270710). We performed exome analysis of the patient described in 2009, and one of the original twins from 1987, the only patients available from the literature. No single genetic etiology exists that explains Fitzsimmons syndrome; however, multiple different genetic causes were identified. Specifically, the twins described by Fitzsimmons had heterozygous mutations in the SACS gene, the gene responsible for autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS), as well as a heterozygous mutation in the TRPS1, the gene responsible in Trichorhinophalangeal syndrome type 1 (TRPS1 type 1) which includes brachydactyly as a feature. A TBL1XR1 mutation was identified in the patient described in 2009 as contributing to his cognitive impairment and autistic features with no genetic cause identified for his spasticity or brachydactyly. The findings show that these individuals have multiple different etiologies giving rise to a similar phenotype, and that "Fitzsimmons syndrome" is in fact not one single syndrome. Over time, we anticipate that continued careful phenotyping with concomitant genome-wide analysis will continue to identify the causes of many rare syndromes, but it will also highlight that previously delineated clinical entities are, in fact, not syndromes at all. © 2016 Wiley Periodicals, Inc.

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Relaxin deficiency attenuates pregnancy-induced adaptation of the mesenteric artery to angiotensin II in mice

Pregnancy is associated with reduced peripheral vascular resistance, underpinned by changes in endothelial and smooth muscle function. Failure of the maternal vasculature to adapt correctly leads to serious pregnancy complications, such as preeclampsia. The peptide hormone relaxin regulates the maternal renal vasculature during pregnancy; however, little is known about its effects in other vascular beds. This study tested the hypothesis that functional adaptation of the mesenteric and uterine arteries during pregnancy will be compromised in relaxin-deficient (Rln^–/–) mice. Smooth muscle and endothelial reactivity were examined in small mesenteric and uterine arteries of nonpregnant (estrus) and late-pregnant (day 17.5) wild-type (Rln^+/+) and Rln^–/– mice using wire myography. Pregnancy per se was associated with significant reductions in contraction to phenylephrine, endothelin-1, and ANG II in small mesenteric arteries, while sensitivity to endothelin-1 was reduced in uterine arteries of Rln^+/+ mice. The normal pregnancy-associated attenuation of ANG II-mediated vasoconstriction in mesenteric arteries did not occur in Rln^–/– mice. This adaptive failure was endothelium-independent and did not result from altered expression of ANG II receptors or regulator of G protein signaling 5 (Rgs5) or increases in reactive oxygen species generation. Inhibition of nitric oxide synthase with l-NAME enhanced ANG II-mediated contraction in mesenteric arteries of both genotypes, whereas blockade of prostanoid production with indomethacin only increased ANG II-induced contraction in arteries of pregnant Rln^+/+ mice. In conclusion, relaxin deficiency prevents the normal pregnancy-induced attenuation of ANG II-mediated vasoconstriction in small mesenteric arteries. This is associated with reduced smooth muscle-derived vasodilator prostanoids.

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Mapping the calcitonin receptor in human brain stem

The calcitonin receptor (CTR) is relevant to three hormonal systems: amylin, calcitonin, and calcitonin gene-related peptide (CGRP). Receptors for amylin and calcitonin are targets for treating obesity, diabetes, and bone disorders. CGRP receptors represent a target for pain and migraine. Amylin receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract, the hypoglossal nucleus, the cuneate nucleus, spinal trigeminal nucleus, the gracile nucleus, and the inferior olivary nucleus. CTR staining was also observed in the area postrema, the lateral reticular nucleus, and the pyramidal tract. The extensive expression of CTR in the medulla suggests that CTR may be involved in a wider range of functions than currently appreciated.

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Ischemic preconditioning reduces hemodynamic response during metaboreflex activation

Ischemic preconditioning (IP) has been shown to improve exercise performance and to delay fatigue. However, the precise mechanisms through which IP operates remain elusive. It has been hypothesized that IP lowers the sensation of fatigue by reducing the discharge of group III and IV nerve endings, which also regulate hemodynamics during the metaboreflex. We hypothesized that IP reduces the blood pressure response during the metaboreflex. Fourteen healthy males (age between 25 and 48 yr) participated in this study. They underwent the following randomly assigned protocol: postexercise muscle ischemia (PEMI) test, during which the metaboreflex was elicited after dynamic handgrip; control exercise recovery session (CER) test; and PEMI after IP (IP-PEMI) test. IP was obtained by occluding forearm circulation for three cycles of 5 min spaced by 5 min of reperfusion. Hemodynamics were evaluated by echocardiography and impedance cardiography. The main results were that after IP the mean arterial pressure response was reduced compared with the PEMI test (means ± SD +3.37 ± 6.41 vs. +9.16 ± 7.09 mmHg, respectively). This was the consequence of an impaired venous return that impaired the stroke volume during the IP-PEMI more than during the PEMI test (–1.43 ± 15.35 vs. +10.28 ± 10.479 ml, respectively). It was concluded that during the metaboreflex, IP affects hemodynamics mainly because it impairs the capacity to augment venous return and to recruit the cardiac preload reserve. It was hypothesized that this is the consequence of an increased nitric oxide production, which reduces the possibility to constrict venous capacity vessels.

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Genetic and pharmacological evidence for low-abundance TRPV3 expression in primary vagal afferent neurons

Primary vagal afferent neurons express a multitude of thermosensitive ion channels. Within this family of ion channels, the heat-sensitive capsaicin receptor (TRPV1) greatly influences vagal afferent signaling by determining the threshold for action-potential initiation at the peripheral endings, while controlling temperature-sensitive forms of glutamate release at central vagal terminals. Genetic deletion of TRPV1 does not completely eliminate these temperature-dependent effects, suggesting involvement of additional thermosensitive ion channels. The warm-sensitive, calcium-permeable, ion channel TRPV3 is commonly expressed with TRPV1; however, the extent to which TRPV3 is found in vagal afferent neurons is unknown. Here, we begin to characterize the genetic and functional expression of TRPV3 in vagal afferent neurons using molecular biology (RT-PCR and RT-quantitative PCR) in whole nodose and isolated neurons and fluorescent calcium imaging on primary cultures of nodose ganglia neurons. We confirmed low-level TRPV3 expression in vagal afferent neurons and observed direct activation with putative TRPV3 agonists eugenol, ethyl vanillin (EVA), and farnesyl pyrophosphate (FPP). Agonist activation stimulated neurons also containing TRPV1 and was blocked by ruthenium red. FPP sensitivity overlapped with EVA and eugenol but represented the smallest percentage of vagal afferent neurons, and it was the only agonist that did not stimulate neurons from TRPV3^–/–1 mice, suggesting FPP has the highest selectivity. Further, FPP was predictive of enhanced responses to capsaicin, EVA, and eugenol in rats. From our results, we conclude TRPV3 is expressed in a discrete subpopulation of vagal afferent neurons and may contribute to vagal afferent signaling either directly or in combination with TRPV1.

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In vivo and in vitro degradation of peptide YY3-36 to inactive peptide YY3-34 in humans

Peptide YY (PYY) is a 36-amino-acid peptide released from enteroendocrine cells upon food intake. The NH₂ terminally truncated metabolite, PYY_3–36, exerts anorexic effects and has received considerable attention as a possible antiobesity drug target. The kinetics and degradation products of PYY metabolism are not well described. A related peptide, neuropeptide Y, may be degraded from the COOH terminus, and in vivo studies in pigs revealed significant COOH-terminal degradation of PYY. We therefore investigated PYY metabolism in vitro after incubation in human blood and plasma and in vivo after infusion of PYY_1–36 and PYY_3–36 in eight young, healthy men. A metabolite, corresponding to PYY_3–34, was formed after incubation in plasma and blood and during the infusion of PYY. PYY_3–34 exhibited no agonistic or antagonistic effects on the Y2 receptor. PYY_1–36 infused with and without coadministration of sitagliptin was eliminated with half-lives of 10.1 ± 0.5 and 9.4 ± 0.8 min (means ± SE) and metabolic clearance rates of 15.7 ± 1.5 and 14.1 ± 1.1 ml·kg^–1·min^–1 after infusion, whereas PYY_3–36 was eliminated with a significantly longer half-life of 14.9 ± 1.3 min and a metabolic clearance rate of 9.4 ± 0.6 ml·kg^–1·min^–1. We conclude that, upon intravenous infusion in healthy men, PYY is inactivated by cleavage of the two COOH-terminal amino acids. In healthy men, PYY_3–36 has a longer half-life than PYY_1–36.

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Complex reinnervation pattern after unilateral renal denervation in rats

Renal denervation (DNX) is a treatment for resistant arterial hypertension. Efferent sympathetic nerves regrow, but reinnervation by renal afferent nerves has only recently been shown in the renal pelvis of rats after unilateral DNX. We examined intrarenal perivascular afferent and sympathetic efferent nerves after unilateral surgical DNX. Tyrosine hydroxylase (TH), CGRP, and smooth muscle actin were identified in kidney sections from 12 Sprague-Dawley rats, to distinguish afferents, efferents, and vasculature. DNX kidneys and nondenervated kidneys were examined 1, 4, and 12 wk after DNX. Tissue levels of CGRP and norepinephrine (NE) were measured with ELISA and mass spectrometry, respectively. DNX decreased TH and CGRP labeling by 90% and 95%, respectively (P < 0.05) within 1 wk. After 12 wk TH and CGRP labeling returned to baseline with a shift toward afferent innervation (P < 0.05). Nondenervated kidneys showed a doubling of both labels within 12 wk (P < 0.05). CGRP content decreased by 72% [3.2 ± 0.3 vs. 0.9 ± 0.2 ng/g_kidney; P < 0.05] and NA by 78% [1.1 ± 0.1 vs. 0.2 ± 0.1 pmol/mg_kidney; P < 0.05] 1 wk after DNX. After 12 wk, CGRP, but not NE, content in DNX kidneys was fully recovered, with no changes in the nondenervated kidneys. The use of phenol in the DNX procedure did not influence this result. We found morphological reinnervation and transmitter recovery of afferents within 12 wk after DNX. Despite morphological evidence of sympathetic regrowth, NE content did not fully recover. These results suggest a long-term net surplus of afferent influence on the DNX kidney may be contributing to the blood pressure lowering effect of DNX.

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Development of ovine chorionic somatomammotropin hormone-deficient pregnancies

Intrauterine growth restriction (IUGR) is a leading cause of neonatal mortality and morbidity. Chorionic somatomammotropin hormone (CSH), a placenta-specific secretory product found at high concentrations in maternal and fetal circulation throughout gestation, is significantly reduced in human and sheep IUGR pregnancies. The objective of this study was to knock down ovine CSH (oCSH) expression in vivo using lentiviral-mediated short-hairpin RNA to test the hypothesis that oCSH deficiency would result in IUGR of near-term fetal lambs. Three different lentiviral oCSH-targeting constructs were used and compared with pregnancies (n = 8) generated with a scrambled control (SC) lentiviral construct. Pregnancies were harvested at 135 days of gestation. The most effective targeting sequence, "target 6" (tg6; n = 8), yielded pregnancies with significant reductions (P ≤ 0.05) in oCSH mRNA (50%) and protein (38%) concentrations, as well as significant reductions (P ≤ 0.05) in placental (52%) and fetal (32%) weights compared with the SC pregnancies. Fetal liver weights were reduced 41% (P ≤ 0.05), yet fetal liver insulin-like growth factor-I (oIGF1) and -II mRNA concentrations were reduced (P ≤ 0.05) 82 and 71%, respectively, and umbilical artery oIGF1 concentrations were reduced 62% (P ≤ 0.05) in tg6 pregnancies. Additionally, fetal liver oIGF-binding protein (oIGFBP) 2 and oIGFBP3 mRNA concentrations were reduced (P ≤ 0.05), whereas fetal liver oIGFBP1 mRNA concentration was not impacted nor was maternal liver oIGF and oIGFBP mRNA concentrations or uterine artery oIGF1 concentrations (P ≥ 0.10). Based on our results, it appears that oCSH deficiency does result in IUGR, by impacting placental development as well as fetal liver development and function.

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Nonlinear identification of the total baroreflex arc: chronic hypertension model

The total baroreflex arc is the open-loop system relating carotid sinus pressure (CSP) to arterial pressure (AP). Its linear dynamic functioning has been shown to be preserved in spontaneously hypertensive rats (SHR). However, the system is known to exhibit nonlinear dynamic behaviors. The aim of this study was to establish nonlinear dynamic models of the total arc (and its subsystems) in hypertensive rats and to compare these models with previously published models for normotensive rats. Hypertensive rats were studied under anesthesia. The vagal and aortic depressor nerves were sectioned. The carotid sinus regions were isolated and attached to a servo-controlled piston pump. AP and sympathetic nerve activity were measured while CSP was controlled via the pump using Gaussian white noise stimulation. Second-order, nonlinear dynamics models were developed by application of nonparametric system identification to a portion of the measurements. The models of the total arc predicted AP 21–43% better (P < 0.005) than conventional linear dynamic models in response to a new portion of the CSP measurement. The linear and nonlinear terms of these validated models were compared with the corresponding terms of an analogous model for normotensive rats. The nonlinear gains for the hypertensive rats were significantly larger than those for the normotensive rats [–0.38 ± 0.04 (unitless) vs. –0.22 ± 0.03, P < 0.01], whereas the linear gains were similar. Hence, nonlinear dynamic functioning of the sympathetically mediated total arc may enhance baroreflex buffering of AP increases more in SHR than normotensive rats.

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Cardiorespiratory upregulation during seawater acclimation in rainbow trout: effects on gastrointestinal perfusion and postprandial responses

Increased gastrointestinal blood flow is essential for euryhaline fishes to maintain osmotic homeostasis during the initial phase of a transition from freshwater to seawater. However, the cardiorespiratory responses and hemodynamic changes required for a successful long-term transition to seawater remain largely unknown. In the present study, we simultaneously measured oxygen consumption rate (M_O2), cardiac output (CO), heart rate (HR), and gastrointestinal blood flow (GBF) in rainbow trout (Oncorhynchus mykiss) acclimated to either freshwater or seawater for at least 6 wk. Seawater-acclimated trout displayed significantly elevated M_O2 (day: 18%, night: 19%), CO (day: 22%, night: 48%), and GBF (day: 96%, night: 147%), demonstrating that an overall cardiorespiratory upregulation occurs during seawater acclimation. The elevated GBF was achieved via a combination of increased CO, mediated through elevated stroke volume (SV), and a redistribution of blood flow to the gastrointestinal tract. Interestingly, virtually all of the increase in CO of seawater-acclimated trout was directed to the gastrointestinal tract. Although unfed seawater-acclimated trout displayed substantially elevated cardiorespiratory activity, the ingestion of a meal resulted in a similar specific dynamic action (SDA) and postprandial GBF response as in freshwater-acclimated fish. This indicates that the capacity for the transportation of absorbed nutrients, gastrointestinal tissue oxygen delivery, and acid-base regulation is maintained during digestion in seawater. The novel findings presented in this study clearly demonstrate that euryhaline fish upregulate cardiovascular function when in seawater, while retaining sufficient capacity for the metabolic and cardiovascular changes associated with the postprandial response.

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Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation

Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [¹⁴C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [¹⁴C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14, and 18 ml/min for 1 h each. At each maternal flow rate, fetal flow rates were set at 3, 6, and 9 ml/min for 20 min each. Appearance of [¹⁴C]phenylalanine was measured in the maternal and fetal venous exudates. Computational modeling of phenylalanine transfer was undertaken to allow comparison of the experimental data with predicted phenylalanine uptake and transfer under different initial assumptions. Placental uptake (mol/min) of [¹⁴C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [¹⁴C]phenylalanine to the fetal circulation was not associated with fetal or maternal flow. The absence of a relationship between placental phenylalanine uptake and net flux of phenylalanine to the fetal circulation suggests that factors other than flow or transporter-mediated uptake are important determinants of phenylalanine transfer. These observations could be explained by tight regulation of free amino acid levels within the placenta or properties of the facilitated transporters mediating phenylalanine transport. We suggest that amino acid metabolism, primarily incorporation into protein, is controlling free amino acid levels and, thus, placental transfer.

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Corrigendum

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2016 CASEM Poster Presentations

No abstract available

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Complications and Adverse Events of a Randomized Clinical Trial Comparing 3 Graft Types for ACL Reconstruction

Objective: Complications/adverse events of anterior cruciate ligament (ACL) surgery are underreported, despite pooled level 1 data in systematic reviews. All adverse events/complications occurring within a 2-year postoperative period after primary ACL reconstruction, as part of a large randomized clinical trial (RCT), were identified and described. Design: Prospective, double-blind randomized clinical trial. Patients and the independent trained examiner were blinded to treatment allocation. Setting: University-based orthopedic referral practice. Patients: Three hundred thirty patients (14-50 years; 183 males) with isolated ACL deficiency were intraoperatively randomized to ACL reconstruction with 1 autograft type. Graft harvest and arthroscopic portal incisions were identical. Intervention: Patients were equally distributed to patellar tendon (PT), quadruple-stranded hamstring tendon (HT), and double-bundle (DB) hamstring autograft ACL reconstruction. Main Outcome Measures: Adverse events/complications were patient reported, documented, and diagnoses confirmed. Results: Two major complications occurred: pulmonary embolism and septic arthritis. Twenty-four patients (7.3%) required repeat surgery, including 25 separate operations: PT = 7 (6.4%), HT = 9 (8.2%), and DB = 8 (7.3%). Repeat surgery was performed for meniscal tears (3.6%; n = 12), intra-articular scarring (2.7%; n = 9), chondral pathology (0.6%; n = 2), and wound dehiscence (0.3%; n = 1). Other complications included wound problems, sensory nerve damage, muscle tendon injury, tibial periostitis, and suspected meniscal tears and chondral lesions. Overall, more complications occurred in the HT/DB groups (PT = 24; HT = 31; DB = 45), but more PT patients complained of moderate or severe kneeling pain (PT = 17; HT = 9; DB = 4) at 2 years. Conclusions: Overall, ACL reconstructive surgery is safe. Major complications were uncommon. Secondary surgery was necessary 7.3% of the time for complications/adverse events (excluding graft reinjury or revisions) within the first 2 years. Level of Evidence: Level 1 (therapeutic studies). Clinical Relevance: This article reports on the complications/adverse events that were prospectively identified up to 2 years postoperatively, in a defined patient population participating in a large double-blind randomized clinical trial comparing PT, single-bundle hamstring, and DB hamstring reconstructions for ACL rupture.

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Shoe and Field Surface Risk Factors for Acute Lower Extremity Injuries Among Female Youth Soccer Players

Objective: To describe acute lower extremity injuries and evaluate extrinsic risk factors in female youth soccer. Design: Nested case–control study. Setting: Youth soccer clubs in Seattle, WA. Participants: Female soccer players (n = 351) ages 11 to 15 years randomly selected from 4 soccer clubs from which 83% of their players were enrolled with complete follow-up for 92% of players. Interventions: Injured players were interviewed regarding injury, field surface, shoe type, and position. Uninjured controls, matched on game or practice session, were also interviewed. Main Outcome Measures: The association between risk factors and acute lower extremity injury using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). Results: One hundred seventy-three acute lower extremity injuries occurred involving primarily the ankle (39.3%), knee (24.9%), and thigh (11.0%). Over half (52.9%) recovered within 1 week, whereas 30.2% lasted beyond 2 weeks. During practices, those injured were approximately 3-fold (OR, 2.83; 95% CI, 1.49-5.31) more likely to play on grass than artificial turf and 2.4-fold (95% CI, 1.03-5.96) more likely to wear cleats on grass than other shoe and surface combinations. During games, injured players were 89% (95% CI, 1.03-4.17) more likely to play defender compared with forward. Conclusions: Half of the acute lower extremity injuries affected the ankle or knee. Grass surface and wearing cleats on grass increased training injuries. Clinical Relevance: The majority, 64%, of female youth soccer players' acute injuries involve the ankle and knee and injury prevention strategies in this age group should target these areas. When considering playing surfaces for training, communities and soccer organizations should consider the third-generation artificial turf a safe alternative to grass.

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Three-Year Outcome After a 1-Month Physiotherapy Program of Local and Individualized Global Treatment for Patellofemoral Pain Followed by Self-Management

Objective: The main aim of this study was to assess whether improvements after a 1-month patellofemoral pain (PFP) program addressing local and global deficits were maintained for 3 years. Design: This prospective cohort study comprised 4 treatment phases including a randomized trial during week 1. Setting: The study was conducted in a private physiotherapy practice. Patients: Thirty-seven patients (55 knees) from an original cohort of 41 patients (60 knees) with PFP were followed for 3 years after referral by doctors to participate in this study. Interventions: Patients received 4 treatments: local treatment focusing on quadriceps strengthening, quadriceps stretching, and taping for fortnight 1, supplemented with individualized global treatment focusing on lower limb posture and movement patterns for fortnight 2, followed by ongoing self-management. Main Outcome Measures: Seven outcome measures, assessed at 4 time points, were quadriceps strength, quadriceps length, eccentric knee control, and 4 pain measures. Long-term measures included return to sporting activity, pain recurrence, exercise compliance, and Kujala score. Results: Improvements after fortnight 1 (P

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Physical Activity and Risk of Lung Cancer: A Meta-analysis

Objective: Previous studies concerning the association between physical activity (PA) and risk of lung cancer yielded mixed results. We investigated the association by performing a meta-analysis. Data Sources: Relevant studies were identified by searching PubMed and EMBASE to January 2014. Twelve cohort studies and 6 case–control studies involving 2 468 470 participants and 26 453 cases of lung cancer were selected for meta-analysis. Main Results: We calculated the summary relative risk (RR) and 95% confidence intervals (CIs) using random-effects models. The analyses showed that individuals who participated in any amount of PA had an RR of 0.79 (95% CI, 0.73-0.86) for risk of lung cancer. Those who participated in high PA (vs low PA) had an RR of 0.75 (95% CI, 0.68-0.84). Stratifying by study design (case–control and cohort studies), smoking status (current, former, and never smokers), and gender, similar inverse associations were found for all the subgroups except for never smokers subgroup. Conclusions: Pooled results from observational studies support a protective effect of PA against lung cancer.

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Climbing Has a Positive Impact on Low Back Pain: A Prospective Randomized Controlled Trial

Objective: Comparison of climbing versus no treatment to treat chronic low back pain. Design: Prospective randomized controlled trial. Setting: Tertiary. Participants: A total of 30 patients with chronic low back pain were recruited and randomly assigned to 2 different groups: climbing and control. The inclusion criteria were defined as chronic low back pain, age between 18 and 45 years, body mass index lower than 25, and no climbing experience. Interventions: Patients in the climbing group were instructed to climb 5 different climbing routes. A climbing activity of 10 sessions in 8 weeks, at least once a week with a minimum duration of 1 hour, was mandatory. Main Outcome Measures: The participants were examined before (T0) and after therapy (8 weeks, T8) and after another 6 weeks (T14). The outcome was evaluated using Oswestry Disability Index, Visual Analog Scale (VAS), Likert scale, and magnetic resonance imaging (MRI). Radiologists evaluating MRI were blinded. The study was performed as a single-center study. Results: Evaluating the Oswestry Disability Index, a significant difference in the time course between the 2 groups was detected (P = 0.022). Significant improvements comparing climbing and control group were also found when assessing VAS in a minimal finger-floor-distance position (P = 0.048). Patients in the climbing group showed a reduction in size of disc protrusion. Conclusions: Climbing may be an effective and low-cost therapy option for people with chronic low back pain. Clinical Relevance: Low back pain is a very common disease but still a challenge to treat. Therapy strategies vary from conservative ones, pharmacological treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and weak opioids, to invasive treatment with acupuncture, injections, and operative reconstruction. Some can be costly and not without risks. For instance, many people who use NSAIDs are at risk of common side effects such as gastrointestinal complications (irritation, ulcers, and bleeding) that may lead to hospitalization. Climbing could offer reduction of pain and better performance in daily life, because it offers a closed chain muscle training that has the potential to improve posture, perception of the trunk midline, and muscle control. Climbing may also lead to a better adherence to continuing treatment than traditional physical therapy and exercise due to a more exciting aspect of the sports activity.

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Clay-Shoveler Fracture in a Paddler: A Case Report

Abstract: Clay-shoveler fracture is a fracture of the spinous process of lower cervical and upper thoracic vertebrae. It has only rarely been reported as being caused by an overuse sports injury. This case report describes the first reported clay-shoveler fracture in a paddler. A 51-year-old male paddler, preparing for a paddling adventure over 630 km, felt a click and a sharp pain paravertebrally on the level of the upper thoracic vertebrae while paddling. Sonar investigation did not reveal any muscular injury but computed tomography revealed a fracture of the spinous process of T1. In this case, it is a stress injury due to excessive paddling over a short period of time. This fracture causes debilitating pain in the acute phase and is mainly treated conservatively.

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High School Football Players' Knowledge and Attitudes About Concussions

Objectives: To assess high school (HS) football players' knowledge of concussions and to determine whether increased knowledge is correlated with better attitudes toward reporting concussion symptoms and abstaining from play. Design: Two survey tools were used to assess athletes' knowledge and attitudes about concussions. Surveys collected information about demographics, knowledge about concussions, and attitudes about playing sports after a concussion. All athletes present completed one of the 2 surveys. A knowledge and attitude score for each survey was calculated. Frequencies and mean values were used to characterize the population; regression analysis, analysis of variance, and t tests were used to look for associations. Setting: A football camp for HS athletes in the Cincinnati area. Participants: Male HS football players from competitive football programs in the Cincinnati area. Intervention: None. Main Outcome Measure: Scores on knowledge and attitude sections; responses to individual questions. Results: One hundred twenty (100%) athletes were enrolled although not every athlete responded to every question. Thirty (25%) reported history of a concussion; 82 (70%) reported receiving prior concussion education. More than 75% correctly recognized all concussion symptoms that were asked, except "feeling in a fog" [n = 63 (53%)]. One hundred nine (92%) recognized a risk of serious injury if they return to play too quickly. Sixty-four (54%) athletes would report symptoms of a concussion to their coach; 62 (53%) would continue to play with a headache from an injury. There was no association between knowledge score and attitude score (P = 0.08). Conclusions: Despite having knowledge about the symptoms and danger of concussions, many HS football athletes in our sample did not have a positive attitude toward reporting symptoms or abstaining from play after a concussion. Clinical Relevance: Physicians should be aware that young athletes may not report concussion symptoms.

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2016 CASEM Injury Prevention Poster Presentations

No abstract available

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Hip Strength Testing of Soccer Players With Long-Standing Hip and Groin Pain: What are the Clinical Implications of Pain During Testing?

Objective: To investigate whether self-reported pain during hip strength testing correlates to a large degree with hip muscle strength in soccer players with long-standing unilateral hip and groin pain. Design: Cross-sectional study. Setting: Clinical assessments at Sports Orthopaedic Research Center-Copenhagen (SORC-C), Arthroscopic Centre Amager, Copenhagen University Hospital, Denmark. Participants: Twenty-four male soccer players with unilateral long-standing hip and groin pain. Interventions: The soccer players performed 5 reliable hip muscle strength tests (isometric hip flexion, adduction, abduction, isometric hip flexion–modified Thomas test, and eccentric hip adduction). Main Outcome Measures: Muscle strength was measured with a hand-held dynamometer, and the players rated the pain during testing on a numerical rating scale (0-10). Results: In 4 tests (isometric hip adduction, abduction, flexion, and eccentric adduction), no significant correlations were found between pain during testing and hip muscle strength (Spearman rho = −0.28 to 0.06, P = 0.09-0.39). Isometric hip flexion (modified Thomas test position) showed a moderate negative correlation between pain and hip muscle strength (Spearman rho = −0.44, P = 0.016). Conclusions: Self-reported pain during testing does not seem to correlate with the majority of hip muscle strength tests used in soccer players with long-standing hip and groin pain.

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Effects of Competition Rule Changes on the Incidence of Head Kicks and Possible Concussions in Taekwondo

Objective: Competition rules related to head kicks (HKs) in sparing-taekwondo (S-TKD) were changed in 2009, resulting in more points awarded to the head attacker. The objective of this research is to measure the incidence of HKs and to analyze the characteristics of situations leading up to and after HKs in a postrule change competition. Design: Descriptive epidemiology study using video analysis. Setting: The final matches of the World Taekwondo Championships (WTCs) in 2011 and 2013. Participants: A total of 1760 athletes participated in both WTCs. Sixty-four athletes, who had won elimination-round matches and were 15 years or older, competed in final matches. Main Outcome Measures: The final matches—a total of 64 matches including 95 rounds—were analyzed using an anatomical and outcome coding scheme for HKs. Results: Overall, a total of 30 athletes experienced receiving one or more HKs during 2 WTCs (469 HKs per 1000 athlete-exposures (A-E), 95% confidence interval = 296, 642). Female athletes showed higher incidences of HKs than male. A trend of increasing incidence of HKs was observed in the females. The HKs occurred more frequently among competitors in lightweight categories and those of similar height (49%). Conclusions: Overall, the frequency of HKs seems to have increased compared with matches before 2009. A sharp increase in the numbers of HKs is evident among the elite female athletes. To prevent receiving an HK, updated game strategies such as training for blocking skills, and safety guidelines for HKs, or revisions to rules are needed. Clinical Relevance: The recent changes to competition rules promoting the use of HKs may have resulted in an increasing frequency of HKs compared with research findings before these changes. Multiple HKs occur frequently in S-TKD; care needs to be taken to avoid possible acute/chronic consequences.

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Frog-Leg Test Maneuver for the Diagnosis of Injuries to the Posterolateral Corner of the Knee: A Diagnostic Accuracy Study

Objective: To determine the sensitivity and specificity of a new clinical test for the diagnosis of injuries to the posterolateral corner of the knee by using magnetic resonance imaging (MRI) as the reference standard. Design: Diagnostic accuracy study. Setting: A tertiary care teaching hospital. Participants: Twelve subjects with chronic instability of the knee and posterolateral corner injury diagnosed by intraoperative findings and 9 subjects without posterolateral corner injury (used as controls). Interventions: Injured and uninjured knees were assessed blindly by 2 examiners using a new clinical diagnostic test (the frog-leg test) and the classic varus stress test. Main Outcome Measures: Injuries to the posterolateral corner of the knee identified by the 2 clinical tests. Findings were compared and examined for reproducibility, and kappa statistic was used to assess interobserver agreement. Test results were compared with those of MRI and intraoperative findings to determine diagnostic accuracy. Results: The frog-leg test showed high interobserver agreement (kappa, 0.86), with a high rate (83%-100%) of agreement with the intraoperative diagnosis. The frog-leg test had high sensitivity (91.7%) and specificity (94.5%) for detecting posterolateral corner injuries. The sensitivity of the varus stress test increased from 83.3% to 90.0% when combined with the frog-leg test. Conclusions: Examiners were able to identify posterolateral corner injuries and differentiate injured from uninjured knees using the frog-leg test, which could potentially be used as an ancillary tool to the varus stress test in diagnosing injuries to the posterolateral corner of the knee. Larger studies are needed to confirm our findings.

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Risk Factors for Noncontact Ankle Injuries in Amateur Male Soccer Players: A Prospective Cohort Study

Objective: To determine whether nonmodifiable and modifiable risk factors [ankle dorsiflexion range of motion (ROM), lower limb power output, and balance], as identified in preseason screening, predict the risk of sustaining a noncontact ankle injury in amateur male soccer players during the training and competitive season. Design: Prospective cohort study. Setting: Amateur soccer competition (club and area representative teams). Participants: Amateur soccer players (n = 210) aged ≥15 years. Assessment of Risk Factors (Independent Variables): Height, weight, ankle dorsiflexion ROM, power (vertical jump) and balance (time of double-leg balanced stance on an electronic wobble board, maximum 20 seconds) measured in preseason screening. Main Outcome Measures (Dependent Variable): Incidence of noncontact ankle injury and exposure to both training and games, monitored during the competitive season following baseline measurement. Noncontact ankle injury was defined as any ankle injury not caused by a collision (with another player or object) resulting in a participant missing at least 1 game or training session. Results: Fourteen of the 210 participants (6.7%) sustained a noncontact ankle injury yielding an injury rate of 0.484 injuries per 1000 player hours. Lower limb power output scores

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Investigating the Feasibility and Utility of Bedside Balance Technology Acutely After Pediatric Concussion: A Pilot Study

Objective: To examine postural instability in children acutely after concussion, using the Wii Balance Board (WBB). We hypothesized that children with traumatic brain injury would have significantly worse balance relative to children without brain injury. Design: Prospective case–control pilot study. Setting: Emergency department of a tertiary urban pediatric hospital. Participants: Cases were a convenience sample 11-16 years old who presented within 6 hours of sustaining concussion. Two controls, matched on gender, height, and age, were enrolled for each case that completed study procedures. Controls were children who presented for a minor complaint that was unlikely to affect balance. Interventions: Not applicable. Main Outcome Measures: The participant's postural sway expressed as the displacement in centimeters of the center of pressure during a timed balance task. Balance testing was performed using 4 stances (single or double limb, eyes open or closed). Results: Three of the 17 (17.6%) cases were too dizzy to complete testing. One stance, double limbs eyes open, was significantly higher in cases versus controls (85.6 vs 64.3 cm, P = 0.04). Conclusions: A simple test on the WBB consisting of a 2-legged standing balance task with eyes open discriminated children with concussion from non-head-injured controls. The low cost and feasibility of this device make it a potentially viable tool for assessing postural stability in children with concussion for both longitudinal research studies and clinical care. Clinical Relevance: These pilot data suggest that the WBB is an inexpensive tool that can be used on the sideline or in the outpatient setting to objectively identify and quantify postural instability.

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Pregame Sore Throat, Postgame Intensive Care Unit

Abstract: A collegiate football athlete presented, on game day, with an acute onset of sore throat. He was afebrile, speaking in full sentences, without signs of respiratory distress. His examination was negative for lymphadenopathy or tonsillar enlargement or exudate. Twelve hours after initial presentation, he developed acute epiglottitis. He underwent urgent fiberoptic intubation and was empirically treated with broad-spectrum antibiotics and corticosteroids. Currently, there are no published reports of acute epiglottitis in athletes. Consequently, there is no evidence to guide return to play decisions. Return to play, following acute epiglottitis, should include resolution of symptoms and a graded return to play, taking into consideration the level of deconditioning the athlete experienced from hospitalization.

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Relationship Between Short Sleep Duration and Preseason Concussion Testing

Objective: Baseline, preseason assessment of cognition, symptoms, and balance has been recommended as part of a comprehensive sport concussion management program. We examined the relationship between sleep and baseline test results. We hypothesized that adolescents who slept fewer hours the night before would report more symptoms and perform more poorly on cognitive testing than students who had a full night sleep. Design: Cross-sectional observation study. Setting: Preseason concussion testing for high school athletes. Participants: A large sample (n = 2928) of student athletes from Maine, USA, between the ages of 13 and 18 years completed preseason testing. Participants with developmental problems, a history of treatment for neurological or psychiatric problems, recent concussion, or 3 or more prior concussions were excluded. Assessment of Risk Factors: Athletes were divided into 4 groups based on their sleep duration the night before testing. Main Outcome Measures: Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT; ImPACT Applications, Inc, Pittsburgh, PA) cognitive composite scores and the embedded Post-Concussion Symptom Scale. Results: Sleep was not related to any ImPACT cognitive composite score, after covarying for age and controlling for multiple comparisons. In contrast, there were sleep duration, sex, and sleep duration by sex effects on the Post-Concussion Symptom Scale. The effect of sleep duration on symptom reporting was more pronounced in girls. Supplementary analyses suggested that sleep insufficiency was associated with a diverse array of postconcussion-like symptoms. Conclusions: Poor sleep the night before baseline or postinjury testing may be an important confound when assessing postconcussion symptoms. Girls may be more vulnerable to experiencing and reporting symptoms following insufficient sleep. Clinical Relevance: Clinicians should routinely ask how the athlete slept the night before preseason baseline testing and consider deferring the symptom assessment or later retesting athletes who slept poorly.

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2016 CASEM Podium Presentations

No abstract available

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Novel developments in field mechanics

Publication date: Available online 1 May 2016
Source:Journal of Human Evolution
Author(s): Adam van Casteren, Vivek Venkataraman, A. Roland Ennos, Peter W. Lucas
Our aim is general: we want to illustrate how much can be gleaned from mechanical measurement in the field. We ask how mechanics may constrain foraging and feeding on both plants and animals, and how various aspects of mechanical behavior could affect the feeding choices that primates make. Here, we present novel methods for the measurement of the material properties and also the employment of tried and tested methods in novel settings. This review demonstrates how mechanical investigation methods can quantify the environmental factors affecting primate locomotion to and from food, which makes up a large part of a primate's daily energy budget. We indicate that, despite the accumulation of much data on the material properties of primate foods, the introduction of new methods is allowing researchers to pursue new avenues of research and change paradigms in primate feeding ecology. Field methods are presented that could aid in the understanding of the extra-oral processing of foodstuffs by primates and enrich further studies into cognition and culture surrounding these types of behavior. We conclude that the use of in-field measurements and a greater understanding of the physics of primate environments are vital and exciting themes integral to the continued understanding of primate evolution and biology.



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Update and Overview of Spinal Injuries in Canadian Ice Hockey, 1943 to 2011: The Continuing Need for Injury Prevention and Education

Objective: To identify spinal injuries in Canadian ice hockey from 2006 to 2011 and to discuss data from 1943 to 2011 and impact of injury prevention programs. Design: Data about spinal injuries with and without spinal cord injury in ice hockey have been collected by ThinkFirst's (now Parachute Canada) Canadian Ice Hockey Spinal Injuries Registry since 1981 through questionnaires from practitioners, ice hockey organizations, and media. Setting: All Canadian provinces and territories. Participants: All registered Canadian ice hockey players. Assessment of Risk Factors: Age, gender, level of play, location, mechanism of injury. Main Outcome Measures: Incidence, incidence rate, prevalence, and nature (morbidity) of the injuries. Results: Between 2006 and 2011, 44 cases occurred, 4 (9.1%) of which were severe. The incidence in the recent years continues to be lower than the peak years. From 1943 to 2011, 355 cases have been documented, primarily males (97.7%) and cervical spine injuries (78.9%), resulting from impact with the boards (64.2%). Check or push from behind (36.0%) was still the most common cause of injury, although slightly lower during 2006 to 2011. From 1943 to 2011, Prince Edward Island, New Brunswick, and British Columbia/Yukon had the highest injury rates. Ontario and Quebec continued to show markedly different injury rates, with Ontario more than twice that of Quebec. Conclusions: Current data for 2006 to 2011 indicate that spinal injuries in ice hockey continue to occur, although still at lower rates than the peak years 1982 to 1995. It is imperative to continue educating players and team officials about spinal injury prevention and to reinforce the rules against checking or pushing from behind to reduce the incidence of these serious injuries.

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2016 CASEM Injury Prevention Podium Presentations

No abstract available

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IOP-details

Publication date: April 2016
Source:International Journal of Psychophysiology, Volume 102





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Editorial Board

Publication date: April 2016
Source:International Journal of Psychophysiology, Volume 102





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Instructions to Authors

Publication date: April 2016
Source:International Journal of Psychophysiology, Volume 102





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Editorial

Publication date: April 2016
Source:International Journal of Psychophysiology, Volume 102





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Assessment of the amount of tooth wear on dental casts and intra-oral photographs

Summary

Tooth wear is a multifactorial condition, leading to the loss of dental hard tissues. Many grading scales are available to assess the amount of tooth wear, one of which is the tooth wear evaluation system (TWES). A grading scale can be used chairside, on casts and on photographs. The aim was to test whether the grading scales of the TWES, used on casts and on photographs, resulted in comparable scores. In addition, it was tested whether these scales can be used to assess tooth wear reliably on photographs. Of 75 tooth wear patients, sets of casts and series of photographs were obtained and graded. Comparison of the grading on casts and on photographs revealed equal median values and percentiles for both occlusal/incisal grading and non-occlusal/non-incisal grading. The grading on casts and on photographs showed a high correlation for the occlusal/incisal grading and a low correlation for the non-occlusal/non-incisal grading (Spearman's rho = 0·74 and rho = 0·47; P < 0·001). Concerning the grading on photographs, the interexaminer reliability was fair-to-good (ICC = 0·41 to ICC = 0·55) while the intra-examiner reliability was fair-to-good to excellent (ICC = 0·68 to ICC = 0·86) for the occlusal/incisal grading. For the non-occlusal/non-incisal grading, the interexaminer reliability was poor to fair-to-good (ICC = 0·22 to ICC = 0·59), while the intra-examiner reliability was fair-to-good to excellent (ICC = 0·64 to ICC = 0·82). It was concluded that the scores obtained with the grading scales of the TWES on casts and on photographs are comparable. The grading scales can be used in a reliable way on photographs, which is especially the case for occlusal/incisal grading.

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Predictors of obstructive sleep apnoea-hypopnea severity and oral appliance therapy efficacy by using lateral cephalometric analysis

Summary

Obstructive sleep apnoea-hypopnea (OSAH) is a common disorder characterised by repetitive complete or partial closure of the upper airway during sleep, which results in sleep fragmentation and oxygen desaturation. There is growing interest in the use of oral appliances (OAs) to treat OSAH. The purpose of this study was to clarify the cephalometric factors that are associated with OSAH severity and that predict the outcome of OA therapy. Two hundred nine patients with OSAH were recruited and analysed retrospectively. They had a polysomnographically documented apnoea-hypopnea index (AHI) of more than five respiratory events per hour. Lateral skull radiographs were used for cephalometric analysis. Only 67 of the 209 recruited patients underwent a second polysomnography (PSG) to evaluate the efficacy of OA therapy. In all recruited patients, the angle formed by the subspinal point (A) to the nasion (N) to the supramental point (B) (i.e. ANB angle) and the distance between the mandibular plane and hyoid bone (MP-H) were predictive factors of OSAH severity. In only 67 patients underwent PSG with an OA, the mean rate of decrease in the AHI was 47·8 ± 29·1%. OA therapy effectively treated OSAH in some patients with a very severe form of OSAH. However, patients who had a high position of the hyoid bone had a poor response to OA therapy. This study suggested that cephalometric analysis is useful for predicting OSAH severity and OA therapy efficacy.

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Is Executive function a significant predictor for risk of fall among elderly population? – A cross sectional study

2016-05-01T11-06-57Z
Source: International Journal of Therapies and Rehabilitation Research
Pereira Adelyn Mathias, Viswambharan Jidesh, Rengaramanujam R. Kanagaraj, Vanitha DSouza.
Abstract Objectives: To evaluate the correlation between executive functions (EF) and the risk of fall among the elderly. Methods: Sixty five elderly fulfilling the criteria were considered in this study. Their EF were assessed using executive interview (EXIT 25) and risk of fall was evaluated by using Elderly falls screening test (EFST). Statistical Analysis was done for the data collected by using Karl Pearsons correlation coefficient. Results: The results show that EF are have a significant moderate positive correlation with the risk of fall. Discussion: This indicating that as there is decline in EF during aging there is increased risk of fall .Therefore evaluation of executive functions should be considered as an important component during the screening for risks of falls in elderly.


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Therapeutic alliances in stroke rehabilitation: A meta-ethnography

Publication date: Available online 30 April 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Helen Michelle Lawton, Gillian Haddock, Paul Conroy, Karen Sage
ObjectiveTo synthesise qualitative studies exploring patients' and professionals' perspectives and experiences of developing and maintaining therapeutic alliances in stroke rehabilitation.Data SourceA systematic literature search was conducted using the following electronic databases: PsychInfo, CINAHL, EMBASE, Medline, AMED, ASSIA, ComDisDome from inception to May 2014. This was supplemented by hand searching, reference tracking, generic web searching and e-mail contact with experts.Study selectionQualitative peer reviewed articles reporting experiences or perceptions of the patient or professional in relation to therapeutic alliance construction and maintenance in stroke rehabilitation were selected for inclusion. Following a process of exclusion, seventeen publications were included in the synthesis.Data extractionAll text identified in the 'results' and 'discussion' sections of the selected studies were extracted verbatim for analysis in a qualitative software programme. Studies were critically appraised independently by two reviewers.Data synthesisArticles were synthesised using a technique of meta-ethnography. Four overarching themes emerged from the process of reciprocal translation: (1) the professional-patient relationship: degree of connectedness; (2) asymmetrical contributions; (3) the process of collaboration: finding the middle ground; and, (4) system drivers.ConclusionThe findings from the meta-ethnography suggest that the balance of power between the patient and professional is asymmetrically distributed in the construction of the alliance. However, given that none of the studies included in the review addressed therapeutic alliance as a primary research area, further research is required to develop a conceptual framework relevant to stroke rehabilitation, in order to determine how this construct contributes to treatment efficacy.



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Empowering Adults with Chronic SCI to Prevent Secondary Conditions

Publication date: Available online 30 April 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Bethlyn Vergo Houlihan, Sarah Everhart-Skeels, Damara Gutnick, Diana Pernigotti, Judi Zazula, Miriam Brody, Sam Burnett, Hannah Mercier, Stathis Hasiotis, Christa Green, Subramani Seetharama, Timothy Belliveau, David Rosenblum, Alan Jette
ObjectiveDevelop and assess the feasibility of My Care My Call (MCMC), an innovative peer-led, community-based telephone intervention for individuals with chronic spinal cord injury (SCI) using Peer Health Coaches (PHCs).DesignQualitative pilot study.SettingGeneral community.ParticipantsConvenience sample of 7 consumer advocates with traumatic SCI 1+ years post-injury.InterventionsMCMC applies a Health Empowerment Approach for goal-setting support, education, and referral to empower consumers in managing their preventive health needs. For feasibility testing, PHCs, trained in Brief Action Planning (BAP), called participants 6 times over 3 weeks.Main Outcome MeasuresIdentified focus areas were: Acceptability, Demand, Implementation, and Practicality. Participant outcome data was collected through brief after-call surveys and qualitative exit interviews. Through a custom website, PHCs documented call attempts, content, and their feedback. Analysis applied the constant comparative method.ResultsMCMC was highly feasible in each focus area for participants. Concerning Acceptability, participants were highly satisfied, rating PHCs as very good or excellent in 80% of calls; felt MCMC was appropriate; and would continue use. Regarding Demand, participants completed 88% of scheduled calls; reported that MCMC fills a real need; and would recommend it. Considering Implementation, PHCs made 119% of expected calls, with larger focus on compiling individualized resources. For Practicality, call duration averaged 29 minutes, with 1 hour of additional time for PHCs. Participant effects including feeling supported, greater confidence towards goals, and greater connection to resources. Subsequently, several process changes enhanced PHC training and support through roleplays, regular support calls, and streamlined MCMC support materials.ConclusionFollowing process changes, a randomized controlled trial to evaluate MCMC is underway.



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EMT/Paramedic - Event Medic Services

Event Medic Services is a National Company providing EMT, Paramedics, SCUBA and Water Rescue personnel for Movie/TV Productions, Concerts, Special Events, Large Construction Sites and Sporting Events. We are currently hiring on a per diem basis for upcoming productions and events in your area.

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Grieving mother questions 911 response

Twenty-one minutes after the first 911 call and about 17 minutes after officials dispatched a unit, Keith Zapoticky was taken to a hospital; he was placed on life support and died two days later

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High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats

Although disorders of mineral metabolism and skeletal muscle are common in chronic kidney disease (CKD), their potential relationship remains unexplored. Elevations in plasma phosphate, parathyroid hormone, and fibroblastic growth factor 23 together with decreased calcitriol levels are common features of CKD. High-phosphate intake is a major contributor to progression of CKD. This study was primarily aimed to determine the influence of high-phosphate intake on muscle and to investigate whether calcitriol supplementation counteracts negative skeletal muscle changes associated with long-term uremia. Proportions and metabolic and morphological features of myosin-based muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of uremic rats (5/6 nephrectomy, Nx) and compared with sham-operated (So) controls. Three groups of Nx rats received either a standard diet (0.6% phosphorus, Nx-Sd), or a high-phosphorus diet (0.9% phosphorus, Nx-Pho), or a high-phosphorus diet plus calcitriol (10 ng/kg 3 day/wk ip, Nx-Pho + Cal) for 12 wk. Two groups of So rats received either a standard diet or a high-phosphorus diet (So-Pho) over the same period. A multivariate analysis encompassing all fiber-type characteristics indicated that Nx-Pho + Cal rats displayed skeletal muscle phenotypes intermediate between Nx-Pho and So-Pho rats and that uremia-induced skeletal muscle changes were of greater magnitude in Nx-Pho than in Nx-Sd rats. In uremic rats, treatment with calcitriol preserved fiber-type composition, cross-sectional size, myonuclear domain size, oxidative capacity, and capillarity of muscle fibers. These data demonstrate that a high-phosphorus diet potentiates and low-dose calcitriol attenuates adverse skeletal muscle changes in long-term uremic rats.

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Local trauma in human patellar tendon leads to widespread changes in the tendon gene expression

Low cellular activity and slow tissue turnover in human tendon may prolong resolution of tendinopathy. This may be stimulated by moderate localized traumas such as needle penetrations, but whether this results in a widespread cellular response in tendons is unknown. In an initial hypothesis-generating study, a trauma-induced tendon cell activity (increased total RNA and collagen I mRNA) was observed after repeated patellar tendon biopsies in young men. In a subsequent controlled study, 25 young men were treated with two 0.8-mm-diameter needle penetrations [n = 13, needle-group (NG)] or one 2.1-mm-diameter needle biopsy [n = 12, biopsy-group (BG)] in one patellar tendon. Four weeks later biopsies were taken from treated (5 mm lateral from trauma site) and contralateral tendons for analyses of RNA content (ribogreen assay), DNA content (PCR based), and gene expression for relevant target genes (Real-time RT-PCR) (NG, n = 11 and BG, n = 8). Intervention increased RNA content, and mRNA expression of collagen I and III and TGF-β1 (P < 0.05), with biopsy treatment having greatest effect (tendency for RNA and collagen I). Results for DNA content were inconclusive, and no changes were detected in expression of insulin-like growth factor-I, connective tissue growth factor, scleraxis, decorin, fibromodulin, tenascin-C, tenomodulin, VEGFa, CD68, IL-6, MMP12, and MMP13. In conclusion, a moderate trauma to a healthy human tendon (e.g., biopsy sampling) results in a widespread upregulation of tendon cell activity and their matrix protein expression. The findings have implications for design of studies on human tendon and may provide perspectives in future treatment strategies in tendinopathy.

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Nitric oxide-mediated vascular function in sepsis using passive leg movement as a novel assessment: a cross-sectional study

Post-cuff occlusion flow-mediated dilation (FMD) is a proposed indicator of nitric oxide (NO) bioavailability and vascular function. FMD is reduced in patients with sepsis and may be a marker of end organ damage and mortality. However, FMD likely does not solely reflect NO-mediated vasodilation, is technically challenging, and often demonstrates poor reproducibility. In contrast, passive leg movement (PLM), a novel methodology to assess vascular function, yields a hyperemic response that is predominately NO-dependent, reproducible, and easily measured. This study evaluated PLM as an approach to assess NO-mediated vascular function in patients with sepsis. We hypothesized that PLM-induced hyperemia, quantified by the increase in leg blood flow (LBF), would be attenuated in sepsis. In a cross-sectional study, 17 subjects in severe sepsis or septic shock were compared with 16 matched healthy controls. Doppler ultrasound was used to assess brachial artery FMD and the hyperemic response to PLM in the femoral artery. FMD was attenuated in septic compared with control subjects (1.1 ± 1.7% vs. 6.8 ± 1.3%; values are means ± SD). In terms of PLM, baseline LBF (196 ± 33 ml/min vs. 328 ± 20 ml/min), peak change in LBF from baseline (133 ± 28 ml/min vs. 483 ± 86 ml/min), and the LBF area under the curve (16 ± 8.3 vs. 143 ± 33) were all significantly attenuated in septic subjects. Vascular function, as assessed by both FMD and PLM, is attenuated in septic subjects compared with controls. These data support the concept that NO bioavailability is attenuated in septic subjects, and PLM appears to be a novel and feasible approach to assess NO-mediated vascular function in sepsis.

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A standard, single dose of inhaled terbutaline attenuates hyperpnea-induced bronchoconstriction and mast cell activation in athletes

Release of bronchoactive mediators from mast cells during exercise hyperpnea is a key factor in the pathophysiology of exercise-induced bronchoconstriction (EIB). Our aim was to investigate the effect of a standard, single dose of an inhaled β₂-adrenoceptor agonist on mast cell activation in response to dry air hyperpnea in athletes with EIB. Twenty-seven athletes with EIB completed a randomized, double-blind, placebo-controlled, crossover study. Terbutaline (0.5 mg) or placebo was inhaled 15 min prior to 8 min of eucapnic voluntary hyperpnea (EVH) with dry air. Pre- and postbronchial challenge, urine samples were analyzed by enzyme immunoassay for 11β-prostaglandin F_2α (11β-PGF_2α). The maximum fall in forced expiratory volume in 1 s of 14 (12–20)% (median and interquartile range) following placebo was attenuated to 7 (5–9)% with the administration of terbutaline (P < 0.001). EVH caused a significant increase in 11β-PGF_2α from 41 (27–57) ng/mmol creatinine at baseline to 58 (43–72) ng/mmol creatinine at its peak post-EVH following placebo (P = 0.002). The rise in 11β-PGF_2α was inhibited with administration of terbutaline: 39 (28–44) ng/mmol creatinine at baseline vs. 40 (33–58) ng/mmol creatinine at its peak post-EVH (P = 0.118). These data provide novel in vivo evidence of mast cell stabilization following inhalation of a standard dose of terbutaline prior to bronchial provocation with EVH in athletes with EIB.

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Cardiorespiratory fitness estimation using wearable sensors: Laboratory and free-living analysis of context-specific submaximal heart rates

In this work, we propose to use pattern recognition methods to determine submaximal heart rate (HR) during specific contexts, such as walking at a certain speed, using wearable sensors in free living, and using context-specific HR to estimate cardiorespiratory fitness (CRF). CRF of 51 participants was assessed by a maximal exertion test (Vo_{2 max}). Participants wore a combined accelerometer and HR monitor during a laboratory-based simulation of activities of daily living and for 2 wk in free living. Anthropometrics, HR while lying down, and walking at predefined speeds in laboratory settings were used to estimate CRF. Explained variance (R²) was 0.64 for anthropometrics, and increased up to 0.74 for context-specific HR (0.73-0.78 when including fat-free mass). Next, we developed activity recognition and walking speed estimation algorithms to determine the same contexts (i.e., lying down and walking) in free living. Context-specific HR in free living was highly correlated with laboratory measurements (Pearson's r = 0.71–0.75). R² for CRF estimation was 0.65 when anthropometrics were used as predictors, and increased up to 0.77 when including free-living context-specific HR (i.e., HR while walking at 5.5 km/h). R² varied between 0.73 and 0.80 when including fat-free mass among the predictors. Root mean-square error was reduced from 354.7 to 281.0 ml/min by the inclusion of context-specific HR parameters (21% error reduction). We conclude that pattern recognition techniques can be used to contextualize HR in free living and estimated CRF with accuracy comparable to what can be obtained with laboratory measurements of HR response to walking.

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Bronchodilating effect of deep inspirations in asthma and chronic cough

The pathophysiologic processes distinguishing classic asthma (CA), cough-variant asthma (CVA), and methacholine (MCh)-induced cough but normal airway sensitivity (COUGH) are inadequately understood and may be a result of differences in the ability to bronchodilate following a deep inspiration (DI). The purpose of this study was to compare the bronchodilating effect of DIs in individuals with CA, CVA, and COUGH using high-dose MCh. Individuals aged 18-65 yr with CA or suspected CVA completed high-dose MCh testing to a maximum change in forced expiratory volume in 1 s (FEV₁) of 50% from baseline (MAX). Impulse oscillometry (IOS) measurements and partial and maximal-flow volume curves (used to calculate a DI index) were recorded at baseline and at each dose of MCh. Body plethysmography was performed at baseline and MAX. Twenty-eight subjects [25 women, 39.8 ± 11.9 yr (means ± SD)] were studied (n = 11 CA, n = 10 CVA, and n = 7 COUGH). At MAX, the percent change in FEV₁ was greater in subjects with CA compared with those with CVA (P < 0.001) and COUGH (P < 0.001), and the percent change in forced vital capacity was greater in those with CA than with COUGH (P = 0.017). Subjects with CA and CVA developed dynamic hyperinflation and gas trapping. In subjects with CA and CVA, all IOS parameters were significantly increased from baseline to MAX, except for central respiratory resistance (R20). In individuals with COUGH, total respiratory resistance, R20, and resonant frequency were significantly increased from baseline. At MAX, the DI index was positive in all groups, suggesting preserved bronchodilation (CA, 0.67 ± 0.97; CVA, 0.51 ± 0.73; COUGH, 0.01 ± 0.36; P = 0.211). We conclude that the bronchodilating effect of DIs is preserved in individuals with CA, CVA, and borderline with COUGH; however, hyperinflation and gas trapping are avoided in subjects with COUGH alone.

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Temperature and blood flow distribution in the human leg during passive heat stress

The influence of temperature on the hemodynamic adjustments to direct passive heat stress within the leg's major arterial and venous vessels and compartments remains unclear. Fifteen healthy young males were tested during exposure to either passive whole body heat stress to levels approaching thermal tolerance [core temperature (T_c) + 2°C; study 1; n = 8] or single leg heat stress (T_c + 0°C; study 2; n = 7). Whole body heat stress increased perfusion and decreased oscillatory shear index in relation to the rise in leg temperature (T_leg) in all three major arteries supplying the leg, plateauing in the common and superficial femoral arteries before reaching severe heat stress levels. Isolated leg heat stress increased arterial blood flows and shear patterns to a level similar to that obtained during moderate core hyperthermia (T_c + 1°C). Despite modest increases in great saphenous venous (GSV) blood flow (0.2 l/min), the deep venous system accounted for the majority of returning flow (common femoral vein 0.7 l/min) during intense to severe levels of heat stress. Rapid cooling of a single leg during severe whole body heat stress resulted in an equivalent blood flow reduction in the major artery supplying the thigh deep tissues only, suggesting central temperature-sensitive mechanisms contribute to skin blood flow alone. These findings further our knowledge of leg hemodynamic responses during direct heat stress and provide evidence of potentially beneficial vascular alterations during isolated limb heat stress that are equivalent to those experienced during exposure to moderate levels of whole body hyperthermia.

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Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias

Lung diffusing capacity for carbon monoxide (DL_CO) is decreased in both usual interstitial pneumonia-idiopathic pulmonary fibrosis (UIP-IPF) and nonspecific interstitial pneumonia (NSIP), but is moderately related to computed tomography (CT)-determined fibrotic changes. This may be due to the relative insensitivity of DL_CO to changes in alveolar membrane diffusive conductance (DM_CO). The purpose of this study was to determine whether measurement of lung diffusing capacity for nitric oxide (DL_NO) better reflects fibrotic changes than DL_CO. DL_NO-DL_CO were measured simultaneously in 30 patients with UIP-IPF and 30 with NSIP. Eighty-one matched healthy subjects served as a control group. The amount of pulmonary fibrosis was estimated by CT volumetric analysis of visually bounded areas showing reticular opacities and honeycombing. DM_CO and pulmonary capillary volume (V_C) were calculated. DL_NO was below the lower limit of normal in all patients irrespective of extent and nature of disease, whereas DL_CO was within the normal range in a nonnegligible number of patients. Both DL_NO and DL_CO were significantly correlated with visual assessment of fibrosis but DL_NO more closely than DL_CO. DM_CO was also below the lower limit of normal in all UIP-IPF and NSIP patients and significantly correlated with fibrosis extent in both diseases, whereas V_C was weakly correlated with fibrosis in UIP-IPF and uncorrelated in NSIP, with normal values in half of patients. In conclusion, measurement of DL_NO may provide a more sensitive evaluation of fibrotic changes than DL_CO in either UIP-IPF or NSIP, because it better reflects DM_CO.

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Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA^Tph2–/–) rats. DA^Tph2–/– rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (~50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA^Tph2–/– rats. Body temperature was also maintained in adult DA^Tph2–/– rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA^Tph2–/– rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat.

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Fatigue-induced adjustment in antagonist coactivation by old adults during a steadiness task

The purpose of this study was to determine the adjustments in the level of coactivation during a steadiness task performed by young and old adults after the torque-generating capacity of the antagonist muscles was reduced by a fatiguing contraction. Torque steadiness (coefficient of variation) and electromyographic activity of the extensor and flexor carpi radialis muscles were measured as participants matched a wrist extensor target torque (10% maximum) before and after sustaining an isometric contraction (30% maximum) with wrist flexors to task failure. Time to failure was similar (P = 0.631) for young (417 ± 121 s) and old (452 ± 174 s) adults. The reduction in maximal voluntary contraction torque (%initial) for the wrist flexors after the fatiguing contraction was greater (P = 0.006) for young (32.5 ± 13.7%) than old (21.8 ± 6.6%) adults. Moreover, maximal voluntary contraction torque for the wrist extensors declined for old (–13.7 ± 12.7%; P = 0.030), but not young (–5.4 ± 13.8%; P = 0.167), adults. Torque steadiness during the matching task with the wrist extensors was similar before and after the fatiguing contraction for both groups, but the level of coactivation increased after the fatiguing contraction for old (P = 0.049) but not young (P = 0.137) adults and was twice the amplitude for old adults (P = 0.002). These data reveal that old adults are able to adjust the amount of antagonist muscle activity independent of the agonist muscle during steady submaximal contractions.

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A low-cost system to easily measure spontaneous physical activity in rodents

Spontaneous physical activity (SPA) can be responsible for variations of a lot of physiological parameters at the molecular, cellular, tissue, and systemic levels. It is increasingly recognized that good understanding of a large part of experimental results requires weighting them by SPA in order to reduce variability and thus to decrease the number of animals necessary to conduct a study. However, because of the high cost of this equipment, only a few laboratories are equipped with such equipment to measure the SPA of their animals. Here we present an effective, adaptable, and affordable system to measure SPA in rodents based on video acquisition of the animal in its own environment. We compared results obtained with our system to those collected at the same time with a commercial system of actimetry recording, and we found a high degree of correlation between these two approaches (r = 0.93; P < 0.001). We also were able to detect small variations of SPA induced by a special environment like chronic hypoxia exposure (25% less spontaneous activity compared with animals in normoxia, P < 0.05) or during the circadian cycle (107% more activity during the nocturnal phase compared with the diurnal phase, P < 0.05).

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Computational neurorehabilitation: modeling plasticity and learning to predict recovery

Despite progress in using computational approaches to inform medicine and neuroscience in the last 30 years, there have been few attempts to model the mechanisms underlying sensorimotor rehabilitation. We argu...

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