The effect of different bed head angles on the hemodynamic parameters of intensive care patients lying in the supine position: A quasi-experimental study.

AIMS: The aim of this study was to research the effect of different bed head angles on the hemodynamic parameters of intensive care patients lying in the supine position. METHODS: This study was a non-randomized and non-controlled, quasi-experimental repeated measures study. The study was conducted with 50 intensive care patients aged 18 and over in a general surgery intensive care unit in Turkey. With each patient in the supine position, the bed head was raised to an angle of 0°, 20°, 30°, and 45° without a pillow, and the hemodynamic parameters of central venous pressure, systolic and diastolic blood pressure, heart rate, breathing rate, and peripheral oxygen saturation were recorded after 0 and 10 min. RESULTS: It was found that the mean central venous pressure value measured at min 0 and 10 was higher when the intensive care patients' bed head angle was raised to 45° than when the bed head was at an angle of 0° or 20° (p < .05). It was found that the patients' other hemodynamic parameters were not affected by different bed head angles. CONCLUSIONS: It was concluded as a result of this research that in intensive care patients in the supine position, only central venous pressure was affected by bed head angle, and that central venous pressure measurement can be reliably made at a bed head angle of 30°.

Neurocraft: software for microscale brain network dynamics.

The brain operates at millisecond timescales but despite of that, the study of its functional networks is approached with time invariant methods. Equally, for a variety of brain conditions treatment is delivered with fixed temporal protocols unable to monitor and follow the rapid progression and therefore the cycles of a disease. To facilitate the understanding of brain network dynamics we developed Neurocraft, a user friendly software suite. Neurocraft features a highly novel signal processing engine fit for tracking evolving network states with superior time and frequency resolution. A variety of analytics like dynamic connectivity maps, force-directed representations and propagation models, allow for the highly selective investigation of transient pathophysiological dynamics. In addition, machine-learning tools enable the unsupervised investigation and selection of key network features at individual and group-levels. For proof of concept, we compared six seizure-free and non seizure-free focal epilepsy patients after resective surgery using Neurocraft. The network features were calculated using 50 intracranial electrodes on average during at least 120 epileptiform discharges lasting less than one second, per patient. Powerful network differences were detected in the pre-operative data of the two patient groups (effect size = 1.27), suggesting the predictive value of dynamic network features. More than one million patients are treated with cardiac and neuro modulation devices that are unable to track the hourly or daily changes in a subject's disease. Decoding the dynamics of transition from normal to abnormal states may be crucial in the understanding, tracking and treatment of neurological conditions. Neurocraft provides a user-friendly platform for the research of microscale brain dynamics and a stepping stone for the personalised device-based adaptive neuromodulation in real-time.

Effects of vestibular neurectomy and neural compensation on head movements in patients undergoing vestibular schwannoma resection.

The vestibular system is vital for maintaining balance and stabilizing gaze and vestibular damage causes impaired postural and gaze control. Here we examined the effects of vestibular loss and subsequent compensation on head motion kinematics during voluntary behavior. Head movements were measured in vestibular schwannoma patients before, and then 6 weeks and 6 months after surgical tumor removal, requiring sectioning of the involved vestibular nerve (vestibular neurectomy). Head movements were recorded in six dimensions using a small head-mounted sensor while patients performed the Functional Gait Assessment (FGA). Kinematic measures differed between patients (at all three time points) and normal subjects on several challenging FGA tasks, indicating that vestibular damage (caused by the tumor or neurectomy) alters head movements in a manner that is not normalized by central compensation. Kinematics measured at different time points relative to vestibular neurectomy differed substantially between pre-operative and 6-week post-operative states but changed little between 6-week and > 6-month post-operative states, demonstrating that compensation affecting head kinematics is relatively rapid. Our results indicate that quantifying head kinematics during self-generated gait tasks provides valuable information about vestibular damage and compensation, suggesting that early changes in patient head motion strategy may be maladaptive for long-term vestibular compensation.

Characterization of patient head motion in otologic surgery: Implications for TEES.

PURPOSE: Middle ear disease is increasingly being managed via transcanal endoscopic ear surgery (TEES). A limitation of TEES is that it restricts the surgeon to single-handed dissection. One solution to this would be an endoscope holder to facilitate two-handed dissection. Current endoscope holders are stationary, and can cause potential damage from endoscope contact with the ossicles or ear canal if unintended head motion occurs from inadequate anesthetic. A dynamic device that could detect and react to patient motion would mitigate these concerns, but currently there is little formal characterization of the frequency, velocity and acceleration of unintended patient head motion during otologic procedures performed under general anesthesia. The present study aims to characterize intraoperative patient head motion kinematics during cases utilizing TEES. MATERIALS AND METHODS: This is a prospective study of adults undergoing otologic procedures performed with general anesthesia and without paralysis. Head motion was characterized using a nine-axis inertial measurement unit (IMU), (LPMS-B2, Life Performance Research) mounted to each patient's forehead for the procedure duration. RESULTS: Data was collected across 10 cases; 50% of patients were female and mean age was 50 ± 14 years. There was observed patient head motion in 40% of cases with maximum linear acceleration of 0.75 m/s2 and angular velocity of 12.50 degrees/s. CONCLUSIONS: Patient movement during otologic procedures was commonly observed, demonstrating the need for a dynamic holder to allow two-handed TEES. Results from this study are the first objective characterization of patient head motion kinematics during otologic procedures performed under general anesthesia.

A Comparison between Mygind and Kaiteki positions in administration of drops to the olfactory cleft.

OBJECTIVES: Topical nasal steroids are a common treatment intervention for olfactory dysfunction. Penetration of topical treatment to the olfactory cleft (OC), such as nasal drops, is greatly dependent on the position of the head when the treatment is administered. We aimed to examine the penetrance of nasal drops to the OC in two different head positions: the Mygind (lying head back) position and the Kaiteki position. DESIGN AND SETTING: The specimens were firstly positioned in Mygind, and thereafter in Kaiteki positions. Nasal drops mixed with blue food dye were administered into the nostrils in each of the head position. Endoscopic videos were recorded, and two blinded observers scored the extent of olfactory cleft penetration (OCP) using a 4-point scale (0 = none, 3 = heavy). PARTICIPANTS: Twelve fresh-frozen cadaver specimens. MAIN OUTCOME MEASURES: Penetration of the dye into the OC. RESULTS: The mean score of nasal drops penetrance to the OC in the Mygind position was 1.34 (standard deviation, SD = 0.92), as compared to 1.76 (SD = 0.65) in the Kaiteki position. The difference in the OCP score between the two groups was not statistically significant (P > .05). CONCLUSION: Both Mygind and Kaiteki head positions are reasonable options for patients considering topical nasal drops for olfaction impairment. The preference of one position over the other should be determined by patient's preference and comfort.

Characterization of patient head motion in otologic surgery: Implications for TEES.

PURPOSE: Middle ear disease is increasingly being managed via transcanal endoscopic ear surgery (TEES). A limitation of TEES is that it restricts the surgeon to single-handed dissection. One solution to this would be an endoscope holder to facilitate two-handed dissection. Current endoscope holders are stationary, and can cause potential damage from endoscope contact with the ossicles or ear canal if unintended head motion occurs from inadequate anesthetic. A dynamic device that could detect and react to patient motion would mitigate these concerns, but currently there is little formal characterization of the frequency, velocity and acceleration of unintended patient head motion during otologic procedures performed under general anesthesia. The present study aims to characterize intraoperative patient head motion kinematics during cases utilizing TEES. MATERIALS AND METHODS: This is a prospective study of adults undergoing otologic procedures performed with general anesthesia and without paralysis. Head motion was characterized using a nine-axis inertial measurement unit (IMU), (LPMS-B2, Life Performance Research) mounted to each patient's forehead for the procedure duration. RESULTS: Data was collected across 10 cases; 50% of patients were female and mean age was 50 ± 14 years. There was observed patient head motion in 40% of cases with maximum linear acceleration of 0.75 m/s2 and angular velocity of 12.50 degrees/s. CONCLUSIONS: Patient movement during otologic procedures was commonly observed, demonstrating the need for a dynamic holder to allow two-handed TEES. Results from this study are the first objective characterization of patient head motion kinematics during otologic procedures performed under general anesthesia.

Trait evolution is reversible, repeatable, and decoupled in the soldier caste of turtle ants.

The scope of adaptive phenotypic change within a lineage is shaped by how functional traits evolve. Castes are defining functional traits of adaptive phenotypic change in complex insect societies, and caste evolution is expected to be phylogenetically conserved and developmentally constrained at broad phylogenetic scales. Yet how castes evolve at the species level has remained largely unaddressed. Turtle ant soldiers (genus Cephalotes), an iconic example of caste specialization, defend nest entrances by using their elaborately armored heads as living barricades. Across species, soldier morphotype determines entrance specialization and defensive strategy, while head size sets the specific size of defended entrances. Our species-level comparative analyses of morphotype and head size evolution reveal that these key ecomorphological traits are extensively reversible, repeatable, and decoupled within soldiers and between soldier and queen castes. Repeated evolutionary gains and losses of the four morphotypes were reconstructed consistently across multiple analyses. In addition, morphotype did not predict mean head size across the three most common morphotypes, and head size distributions overlapped broadly across all morphotypes. Concordantly, multiple model-fitting approaches suggested that soldier head size evolution is best explained by a process of divergent pulses of change. Finally, while soldier and queen head size were broadly coupled across species, the level of head size disparity between castes was decoupled from both queen head size and soldier morphotype. These findings demonstrate that caste evolution can be highly dynamic at the species level, reshaping our understanding of adaptive morphological change in complex social lineages.

Comparison of Techniques for Correction of Chin-down Vertical Abnormal Head Position Associated with Infantile Nystagmus Syndrome.

PURPOSE: We evaluated the relative effectiveness of combined recession-resection of vertical rectus muscles versus superior rectus recession with inferior oblique weakening for patients who underwent surgical correction of chin-down abnormal head position (AHP) associated with infantile nystagmus syndrome (INS). DESIGN: Retrospective interventional case series. METHODS: This is a review of 22 patients who underwent surgical correction of chin-down vertical AHP associated with INS at an academic institution. The primary outcome was collapse of AHP. Unfavorable outcomes included repeat surgery and induced strabismus, in addition to failure of collapse of AHP. RESULTS: Twenty-two patients had chin-down AHP. Recession-resection (bilateral superior rectus recession 6-9 mm; bilateral inferior rectus resection 5-9 mm) was performed in 11 cases; weakening of both elevators (bilateral superior rectus recession 5-8 mm, bilateral inferior oblique recession or myectomy) occurred in 11 cases. Unfavorable outcome rates were 64% (7/11) compared with 18% (2/11), respectively (P = .03). Reoperation was performed for 6 of 22 patients. Five patients were from the recession-resection group, namely 3 for induced V-pattern esotropia, 1 for alternating esotropia, and 1 to correct recurrent AHP. The last of the 6 who required reoperation was in the elevator weakening group, and required correction of a recurrent AHP (P = .06). CONCLUSIONS: While recession-resection of the vertical recti and weakening of both elevators each produce acceptable collapse of chin-down AHP, the former frequently induces a V-pattern esotropia requiring reoperation.

Surgical management of pediatric patients with congenital fibrosis of the extraocular muscles.

PURPOSE: Congenital fibrosis of the extraocular muscles (CFEOM) is a rare nonprogressive disorder characterized by bilateral ptosis, with severely limited ocular motility. We report the treatment outcomes and problems in 3 cases of pediatric CFEOM in which extraocular muscle surgery was performed. CASES: All the cases showed bilateral ptosis and a chin-up abnormal head posture (AHP). Case 1 A 6-year-old girl. Both eyes were fixed downward with esotropia and could not elevate above the horizontal midline. She underwent simultaneous bilateral inferior rectus (IR) and medial rectus (MR) recession. Postoperatively, 8-prism-diopter (PD) exotropia was observed, and the AHP were improved, but MR advancement in the right eye was necessary because A-pattern exotropia became prominent starting about 10 months postoperatively. Case 2 A 7-year-old girl. Both eyes were fixed downward and did not elevate over the midline. She underwent bilateral IR recession. Postoperatively, 8-PD exotropia was observed; however, A-pattern exotropia became prominent gradually at about 1 year and 7 months postoperatively, and bilateral lateral rectus (LR) recession was added. Case 3 A 6-year-old girl. Both eyes were fixed downward but could be elevated above the horizontal midline by upward effort. She underwent bilateral IR recession, which resulted in improvement of the AHP and ptosis. About 8 months postoperatively, exotropia was evident only in the downward gaze. CONCLUSIONS: Bilateral IR recession in pediatric patients with CFEOM was effective in improving AHP, but postoperative exotropia appeared to be inevitable owing to the diminished adducted function caused by IR recession. Thus, horizontal strabismus surgery should be planned after the results of IR recession become evident.

STIMULUS: Noninvasive Dynamic Patterns of Neurostimulation Using Spatio-Temporal Interference.

OBJECTIVE: This paper obtains strategies that can achieve spatially precise noninvasive deep brain stimulation using electrical currents. METHODS: We provide the Spatio-Temporal Interference-based stiMULation focUsing Strategy (STIMULUS) that generates rich patterns of spatiotemporally interfering currents to stimulate precisely and deep inside the brain. To calibrate and compare the accuracy of stimulation using different techniques, we utilize computational Hodgkin-Huxley-type models for neurons and a model of current dispersion in the head. RESULTS: In this computational model, STIMULUS dramatically outperforms the recently proposed Temporal Interference (TI) stimulation strategy in spatial precision. Our results also suggest that STIMULUS can attain steerable and multisite stimulation, which can be important in giving feedback in brain-machine interfaces. Finally, by examining more mammalian neuron types, we also observe that not every neuron exhibits temporal-interference stimulation. CONCLUSIONS: Computer simulations suggest that the proposed STIMULUS strategy has potential to achieve noninvasive electrical deep brain stimulation with high spatial precision and, further, has the flexibility of generating rich stimulation patterns. The fact that some neuron types do not exhibit TI stimulation suggests that caution is needed in evaluating conclusions of application of TI stimulation on large mammalian brains. SIGNIFICANCE: A technique to reliably, noninvasively, and precisely stimulate deep inside the human brain could revolutionize human neuroscience and clinical treatments. We obtain the first computational demonstration of the recently proposed TI stimulation. Advancing on that, we propose a novel strategy that can perform stimulation with high precision and flexibility.

Long-term Outcomes Following Surgery for Infantile Nystagmus Syndrome With Abnormal Head Positioning.

PURPOSE: To evaluate long-term outcomes of surgical treatment for abnormal head positioning (AHP) associated with infantile nystagmus syndrome (INS). DESIGN: Retrospective observational case series. METHODS: Review of 150 patients who underwent surgery for AHP associated with nystagmus. Outcomes included head positioning, duction limitations, and strabismus, and were evaluated several times postoperatively. Successful collapse of AHP was defined as being ≤10°. RESULTS: Thirty-one patients had surgery for AHP in the pitch (chin up/down) position, whereas 119 had surgery for a horizontal AHP. In addition, 54 underwent 50%-60% augmentation, 19 underwent 40% augmentation, 5 underwent less than 40% augmentation. Thirty-eight had surgical dose modified to correct strabismus, and 3 underwent surgery different from standard Kestenbaum procedures. Collapse of AHP: At the 1-3-week follow-up (n = 131), 125 patients (95%) had collapse of AHP. The percentage trended down at the 2-5-month (91%, n = 106) and 2-year follow-ups (83%, n = 57). However, at 5 and 10 years, it was 93% (n = 42) and 93% (n = 14), respectively, due to reoperation in a small minority. Over- and undercorrection: At 1-3 weeks, 5% of patients were overcorrected whereas 0% were undercorrected. Over- and undercorrection rates peaked at 2 years postoperatively. Ten years out, there were no overcorrections and 7% undercorrections. Four percent of patients required reoperation for overcorrection (mean 2.7 years) and 5% did for undercorrection (mean 3.9 years). CONCLUSION: Surgery for the head positioning associated with INS produces excellent outcomes throughout 10 years postoperatively. Overcorrection presents early and resolves either over time or with additional surgery. Undercorrection develops later and can persist despite reoperation.

Management of Strabismus Associated With Infantile Nystagmus Syndrome: A Novel Classification to Assist in Surgical Planning.

PURPOSE: There is no consensus on the surgical management of head position associated with infantile nystagmus syndrome (INS) when strabismus coexists, and few outcome data have been published. We propose classifying strabismus into concordant or discordant based on the relationship between head positioning and strabismus and then modifying surgery accordingly. Our objective is to describe this system and to review surgical outcomes. DESIGN: Retrospective observational case series. METHODS: Twenty-eight patients with INS and coexisting horizontal strabismus underwent surgery for horizontal head positioning and had ≥2 months of follow-up from 1995-2018 at the Vanderbilt Eye Institute. Outcome variables included head positioning (minimal, ≤10°; mild, 11-30°; moderate 31-44°; and severe ≥45°), strabismus (range 0-70 prism diopters [PDs]; minimal ≤10 PD), and reoperation rates. Nonparametric Wilcoxon signed rank, Fisher exact, and Mann-Whitney U tests were used for statistical analysis. RESULTS: Twenty-one cases were concordant and 7 were discordant; the mean follow-up was 4.1 years. Ninety-six percent of patients had moderate to severe head positioning at baseline. Correction rates (to minimal) were 100% at 2-5 months postoperatively and 86% at last follow-up (P < .0001 at both time points compared with preoperatively). The magnitude of strabismus decreased compared with preoperative strabismus (30.8 ± 10.8 PDs; n = 28), strabismus at 2-5 months (9.1 ± 11.9 PDs; P = .0001; n = 26), and last follow-up (12.0 ± 14.1 PDs; P = .0003; n = 28). The overall reoperation rate was 32%. CONCLUSIONS: Our classification system in patients with INS allows a systematic way to surgically improve head positioning and strabismus in cases of moderate to severe baseline head positioning.

VEGF and FGF signaling during head regeneration in hydra.

BACKGROUND: Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) signaling pathways play important roles in the formation of the blood vascular system and nervous system across animal phyla. We have earlier reported VEGF and FGF from Hydra vulgaris Ind-Pune, a cnidarian with a defined body axis, an organized nervous system and a remarkable ability of regeneration. We have now identified three more components of VEGF and FGF signaling pathways from hydra. These include FGF-1, FGF receptor 1 (FGFR-1) and VEGF receptor 2 (VEGFR-2) with a view to deciphering their possible roles in regeneration. METHODS: In silico analysis of proteins was performed using Clustal omega, Swiss model, MEGA 7.0, etc. Gene expression was studied by whole mount in situ hybridization. VEGF and FGF signaling was inhibited using specific pharmacological inhibitors and their effects on head regeneration were studied. RESULTS: Expression patterns of the genes indicate a possible interaction between FGF-1 and FGFR-1 and also VEGF and VEGFR-2. Upon treatment of decapitated hydra with pharmacological inhibitor of FGFR-1 or VEGFR-2 for 48 h, head regeneration was delayed in treated as compared to untreated, control regenerates. When we studied the expression of head specific genes HyBra1 and HyKs1 and tentacle specific gene HyAlx in control and treated regenerates using whole mount in situ hybridization, expression of all the three genes was found to be adversely affected in treated regenerates. CONCLUSIONS: The results suggest that VEGF and FGF signaling play important roles in regeneration of hypostome and tentacles in hydra.

The Effect of Morbidity and Sex on Postnatal Growth of Very Preterm Infants: A Multicenter Cohort Study.

BACKGROUND: Extrauterine growth restriction is common in the preterm infant, and it is associated with poor neurodevelopment. Nutrition plays an important role in postnatal growth, but growth is also influenced by other factors like co-morbidity, and, also, there might be sex differences. METHODS: This is a cohort study including preterm infants < 32 weeks at birth (n = 21,825) from the Spanish Neonatal Network database. The effect of sex and morbidity (patent ductus arteriosus, bronchopulmonary dysplasia, necrotizing enterocolitis and late-onset sepsis) on weight gain as well as linear and head growth from birth to discharge/death was assessed with linear regression models adjusted by gestational age and Z-scores at birth. RESULTS: The 4 selected morbidities had an independent effect on all 6 growth parameters studied, which was greater in the case of necrotizing enterocolitis: changes in weight, length and head Z-scores were -0.60 (95% CI: -0.66 to -0.55), -0.62 (95% CI: -0.70 to -0.54) and -0.63 (95% CI: -0.71 to -0.56), respectively. Weight gain and linear growth were overall more affected than head growth. Girls lost slightly more weight Z-scores (-0.03; 95% CI: -0.06 to -0.002) than boys after adjustment by morbidity. There were no significant gender differences regarding linear and head growth velocity (cm/week), although girls lost more head Z-scores (-0.14; 95% CI: -0.18 to -0.10). CONCLUSIONS: Main co-morbidities associated with prematurity have an impact on postnatal growth. Head growth is less affected than length and weight. Girls are at slightly higher risk of postnatal weight and head restriction after adjustment by morbidity.

FoxN3 is necessary for the development of the interatrial septum, the ventricular trabeculae and the muscles at the head/trunk interface in the African clawed frog, Xenopus laevis (Lissamphibia: Anura: Pipidae).

BACKGROUND: Fox genes are a large family of transcription factors that play diverse roles in the immune system, metabolism, cancer, cell cycle, and animal development. It has been shown that FoxN3 is indispensable for normal craniofacial development in the mouse and the African clawed frog, Xenopus laevis. Morpholino-mediated knockdown of FoxN3 in X. laevis delays overall development of early tadpole stages and causes eye defects, the absence of some cranial nerve branches, and malformations of the cranial skeleton and some cranial muscles, while the skeleton, nerves and muscles of the trunk are unaffected. RESULTS: We report a delay in heart morphogenesis, the absence of the interatrial septum, and a reduction and compaction of the ventricular trabeculation after knockdown of FoxN3 in X. laevis. Furthermore, we found malformations of the cucullaris and diaphragmatico-branchialis muscles, two head muscles that develop in the head/trunk interface of X. laevis. CONCLUSIONS: FoxN3 is necessary for the development of the interatrial septum and trabeculae in the frog heart, as well as the cranial muscles developing in the head/trunk interface. This gives the first evidence for a dependence on the head myogenic program of the cucullaris muscle in an anuran species.

An Investigation of Pressure Ulcer Risk, Comfort, and Pain in Medical Imaging.

INTRODUCTION: Pressure ulcers present significant trauma to patients and are expensive to manage. In medical imaging (MI), no study has been conducted to rigorously investigate interface pressure (IP) risk on MI table surfaces. IP is defined as the pressure between human body and a supporting surface. The aims of this research were to investigate whether IP risks exist on MI table surfaces and to assess pain and comfort when lying on MI table surfaces. METHODS: A calibrated XSENSOR mat was used to measure IP for three jeopardy areas (head, sacrum, and heels) in healthy volunteers on an x-ray table surface with no mattress, an x-ray table surface with a thin radiolucent mattress, and a computed tomography table surface, after which they completed a pain and comfort questionnaire. RESULTS: The sample consisted of 26 females and 23 males aged 18-59 years (mean = 34.6; standard deviation [SD] = 10.5). Analysis of variance identified statistically significant differences in the mean IP for the jeopardy areas across the three MI table surfaces (P ≤ .001). Results also indicated high mean IP value for the head (75.9 mmHg; SD = 6.9) on the x-ray table with no mattress. Seventy percent of the volunteers found lying on the x-ray table with no mattress to be very uncomfortable. Sixty-seven percent experienced most pain whilst lying on the x-ray table with no mattress and over 81% of the pain occurred at the head. CONCLUSION: IP risk exists on x-ray tables with no mattress. This could increase the risk of developing pressure ulcers in patients accessing prolonged radiography/radiology procedures.

Common pathogenic mechanism in patients with dropped head syndrome caused by different mutations in the MYH7 gene.

Mutations in the MYH7 gene are the source of an allelic series of diseases, including various cardiomyopathies and skeletal myopathies that usually manifest in adulthood. We observed a 1.5 y.o. male patient with congenital weaknesses of the axial muscles, "dropped head" syndrome, and dilated cardiomyopathy. The clinical evaluation included medical history, an echocardiogram, electromyography, and a histopathological study. The genetic evaluation included whole exome sequencing. Muscle biopsy samples from the proband were used for mRNA extraction. We revealed a novel genetic variant c.5655 + 5G > C in the MYH7 gene. The analysis of the cDNA showed an in-frame skipping of exon 38 (p.1854_1885del). This variant and two previously published mutations (c.5655G > A and c.5655 + 1G > A), also presumably leading to exon 38 skipping, were studied by expression analysis in the HEK293T cell line transfected with 4 plasmids containing the MYH7 minigene (wt, c.5655G > C, c.5655 + 1G > A and c.5655 + 5G > A). A quantitative difference in expression was shown for cell lines with each of the three mutant plasmids. All mutation carriers had a similar phenotype and included congenital axial myopathy and variable cardiac involvement. Prominent dropped head syndrome was mentioned in all patients. Early-onset axial myopathy with a dropped head syndrome is a distinct clinical entity within MYH7-related disorders. We suggest that mutations in the MYH7 gene affecting the C-terminal domain of beta-myosin heavy chain should also be considered as a possible cause in cases of early-onset myopathy with "dropped head" syndrome.

An evolutionarily-conserved Wnt3/ß-catenin/Sp5 feedback loop restricts head organizer activity in Hydra.

Polyps of the cnidarian Hydra maintain their adult anatomy through two developmental organizers, the head organizer located apically and the foot organizer basally. The head organizer is made of two antagonistic cross-reacting components, an activator, driving apical differentiation and an inhibitor, preventing ectopic head formation. Here we characterize the head inhibitor by comparing planarian genes down-regulated when ß-catenin is silenced to Hydra genes displaying a graded apical-to-basal expression and an up-regulation during head regeneration. We identify Sp5 as a transcription factor that fulfills the head inhibitor properties: leading to a robust multiheaded phenotype when knocked-down in Hydra, acting as a transcriptional repressor of Wnt3 and positively regulated by Wnt/ß-catenin signaling. Hydra and zebrafish Sp5 repress Wnt3 promoter activity while Hydra Sp5 also activates its own expression, likely via ß-catenin/TCF interaction. This work identifies Sp5 as a potent feedback loop inhibitor of Wnt/ß-catenin signaling, a function conserved across eumetazoan evolution.

Identification and characterization of an atypical RIG-I encoded by planarian Dugesia japonica and its essential role in the immune response.

Retinoic acid-inducible gene I (RIG-I), an RNA sensor with a conserved structure, activates the host interferon (IFN) system to produce IFNs and cytokines for eliminating pathogens upon recognizing PAMPs. However, the biological functions and the mechanism by which RIG-I regulates the innate immunity response in invertebrates are still unknown at present. Here we identified an atypical RIG-I in planarian Dugesia japonica. Sequence analysis, 3D structure modeling and phylogenetic analysis showed that this atypical protein was clustered into a single clade at the base of the tree in invertebrates, suggesting that DjRIG-I is an ancient and unique protein of the RIG-I-like receptors (RLRs). In situ hybridization analysis revealed that the DjRIG-I mRNAs were predominantly expressed in the pharynx and head of the adult and regenerative planarians. Stimulation with PAMPs induced the over-expression of DjRIG-I in planarians. The molecular simulation demonstrated that DjRIG-I formed a large hole-structure for the docking of dsRNAs, and the pull-down assay confirmed the interaction between DjRIG-I and viral analog poly(I:C). Importantly, some representative antiviral/antibacterial genes in the RIG-I-mediated IFN and P38 signaling pathway, TBK1, IRF-3, Mx, and P38, were significantly upregulated in planarians stimulated with PAMPs. Interference of the DjRIG-I expression by RNAi, inhibited the PAMPs-induced over-expression, suggesting that DjRIG-I is a key player for downstream signaling events. These results indicate that DjRIG-I triggered the intracellular signaling cascades independent of the classical CARD domains and played an essential role in the virus/bacteria-induced innate immunity of planarian.

Effect of right lateral position with head elevation on tracheal aspirate pepsin in ventilated preterm neonates: randomized controlled trial.

Objective: To evaluate the effect of right lateral positioning in comparison with supine positioning on tracheal aspirate pepsin levels as a marker of aspiration of gastric contents in ventilated preterm neonates. Study design: This randomized controlled trial was conducted on 60 ventilated preterm neonates <35 weeks; 30 neonates were nursed in right lateral position for 6 hours while the other 30 neonates were nursed in supine position for 6 hours. Tracheal aspirate sample was obtained from each neonate in both the groups just after the end of 6 hours and pepsin level was measured. Results: Neonates in right lateral position group had significantly lower tracheal pepsin level than neonates in supine position group (6 ng/ml) interquartile range [IQR] (3-20) versus 15 ng/ml [IQR] (5.5-90) (p = .024). There is positive correlation between tracheal aspirate pepsin level and fraction of inspired oxygen (FiO2) needed during the intervention (r = 0.383, p = .040). There is no correlation between tracheal pepsin level and gestational age, birth weight, or duration of mechanical ventilation and other ventilatory settings. Conclusion: Nursing ventilated premature infants in right lateral position is associated with decreased aspiration of gastric contents.