Migration of sea urchin primordial germ cells

COVER PHOTOGRAPH: EMT and migration of sea urchin PGCs. Live‐cell confocal micrographs of 34 and 43 hour old purple sea urchin, Strongylocentrotus purpuratus, gastrulae. The germline marker, Sp‐Vasa, is yellow and the apical marker, Sp‐ABCG2a, is cyan. From Campanale et al., Developmental Dynamics 243:917–927.     

Clinical anatomy of vertebrae in scoliosis: global analysis in four different diseases by multiplanar reconstructive computed tomography

Background contextFew accurate analyses of clinically useful vertebral anatomy have been conducted, and most have focused on thoracic idiopathic scoliosis.PurposeTo evaluate the different anatomic characteristics in scoliosis by disease type and level.Study designObservational cohort study.Patient sampleForty-eight patients with scoliosis were included in this study.Outcome measuresSubjects underwent computed tomography (CT) of the whole spine.MethodsForty-eight patients with scoliosis were included in this study: 15 adolescent idiopathic, 11 cerebral palsy (CP), 10 muscular dystrophy (MD), and 12 congenital (CG) scoliosis patients with similar demographics. Subjects underwent CT of the whole spine, preoperatively. Eight anatomic parameters were measured in multiplanar reconstructive CT images, and statistical analysis was performed to investigate differences.ResultsIn general, values in the anatomic parameters were similar for the four diseases. Each parameter showed the unique change pattern according to the spinal level regardless of curvature shape, direction, or magnitude. In particular, chord length (CL) in MD and CG scoliosis was lower than in adolescent idiopathic scoliosis (AIS) and CP, and pedicle rib unit length was lower in CG scoliosis than in the other diseases (p<.05). Comparisons of convex and concave anatomies in AIS showed that inner pedicle width (PWI) and outer pedicle width (PWO) were wider for convex side, CL, pedicle width, and transverse pedicle angle were greater for concave side (p<.05), and differences were more significant at apices. However, in CP, PWI and PWO were similar between convex and concaves sides (p>.05). Although PWI and PWO were wider for convex sides and CL and pedicle length were greater for concave sides in MD (p<.05), differences were less significant at apices. Particularly, CG scoliosis showed severely deformed anatomy, with differences of seven parameters at apical vertebrae (p<.05).ConclusionClinical anatomies of vertebrae in scoliosis were found to differ significantly at different levels and in terms of convexity and disease type.     

Predictors of disease-specific quality of life after arthroscopic rotator cuff repair

Purpose

Disease-specific instruments of quality of life (QOL) are more sensitive to disease-specific changes. The purpose of this study is to identify prognostic factors for disease-specific QOL after all-arthroscopic rotator cuff (RC) repair using the Western Ontario Rotator Cuff Index (WORC).

Methods

A total of 140 patients were evaluated after an RC repair with a mean follow-up of 22?±?6.7 months. Evaluations included the WORC, EQ-5D and anchor questions. Preoperative patient demographics and radiologic characteristics were assessed to identify predictors of disease-specific QOL.

Results

Most patients (81.4 %) were satisfied with their surgical result. Minor tear retraction (odds ratio [OR] 2.97, p?=?0.030), male gender (OR 3.67, p?=?0.003), no social benefits (OR 3.67, p?=?0.042) and pre-surgical complaints for more than six months (OR 3.03, p?=?0.021) were independent predictors for superior postoperative WORC score in multivariable analysis. None of these factors were predictive for a higher EQ-5D score.

Conclusion

These findings highlight the important impact of retraction on QOL after RC repair and underline the utility of disease-specific instruments. Future studies should focus on how these significant predictors can be used to improve decision making and to develop new treatment approaches.

     

Contextual interaction of GABAergic circuitry with dynamic synapses

Visual context shapes human perception, yet our understanding of this phenomenon in terms of synaptic circuitry is still rudimentary. Our in vitro experiments with avian tectum reveal two distinct GABAergic pathways that mediate the spatiotemporal tectal interaction of retinal inputs. One pathway mediates postsynaptic lateral inhibition. The other pathway interacts with the synaptic depression of retinotectal synapses. Simulations of an experimentally constrained model including the two pathways reproduce the observed avian tectum wide-field neuron's sensitivity to small and moving stimuli, while being insensitive to whole-field motion.     

Pre-operative Two-Point Discrimination Predicts Response to Carpal Tunnel Release

HSS Journal ® - Limited evidence informs whether pre-operative values of two-point discrimination (2PD) in patients with carpal tunnel syndrome predict response to surgery. The primary aim of...     

An inactive receptor-G protein complex maintains the dynamic range of agonist-induced signaling

Agonist binding promotes activation of G protein-coupled receptors (GPCRs) and association of active receptors with G protein heterotrimers. The resulting active-state ternary complex is the basis for conventional stimulus-response coupling. Although GPCRs can also associate with G proteins before agonist binding, the impact of such preassociated complexes on agonist-induced signaling is poorly understood. Here we show that preassociation of 5-HT₇ serotonin receptors with G_s heterotrimers is necessary for agonist-induced signaling. 5-HT₇ receptors in their inactive state associate with G_s, as these complexes are stabilized by inverse agonists and receptor mutations that favor the inactive state. Inactive-state 5-HT₇–G_s complexes dissociate in response to agonists, allowing the formation of conventional agonist–5-HT₇–G_s ternary complexes and subsequent G_s activation. Inactive-state 5-HT₇–G_s complexes are required for the full dynamic range of agonist-induced signaling, as 5-HT₇ receptors spontaneously activate G_s variants that cannot form inactive-state complexes. Therefore, agonist-induced signaling in this system involves two distinct receptor-G protein complexes, a conventional ternary complex that activates G proteins and an inverse-coupled binary complex that maintains the inactive state when agonist is not present.

G protein-coupled receptors (GPCRs) transduce a wide variety of physiological signals and are targeted by a substantial fraction of all therapeutic drugs (1). GPCRs are conformationally dynamic and transition between inactive and active states, the latter being capable of interacting with and activating heterotrimeric G proteins (2). Although some level of constitutive activity is common, the conformational equilibrium “setpoint” usually favors the inactive state of the receptor, thus keeping the system turned off and ready to respond to agonists. Agonist binding stabilizes active conformations and promotes the formation of transient active-state ternary agonist-receptor-G protein complexes (3). This positive allosteric interaction between agonist and G protein binding is the hallmark of conventional GPCR coupling. Receptor-G protein complexes that form before agonist binding have also been described (4–8) and are generally thought of as a means to promote rapid or specific signaling after agonist binding. However, the properties and functional significance of such “preassociated” complexes are largely unknown, and inactive receptor conformations are generally considered unable to interact with G proteins. Here we show that unliganded 5-HT₇ serotonin receptors form complexes with G_s heterotrimers, and that these complexes help maintain the receptor in an inactive state. Agonist binding leads to dissociation of inactive-state 5-HT₇–G_s complexes, which in turn allows increased formation of active-state 5-HT₇–G_s complexes and G protein activation. Thus, a negative allosteric interaction between agonist and G protein binding is required for the full sensitivity of these receptors to serotonin.     

Effect of increased wall thickness on indices of left ventricular pump function in children.

OBJECTIVE--To investigate whether augmented chamber performance in children with a concentric hypertrophied left ventricle is due to increased myocardial shortening or a geometric effect of the thickened ventricular wall. DESIGN--Chamber performance in terms of fractional area change and myocardial shortening--that is, circumferential midwall shortening--were measured by cross sectional echocardiography in young people with normal left ventricles and those with concentric hypertrophy of the left ventricle. PATIENTS--52 healthy infants, children, and young people (age range 3 1/2 weeks to 26 years; body weight 1.8-89 kg (mean 23.6 kg)) and 29 infants, children, and adolescents with ventricular hypertrophy (mean body weight 31.4 kg, age range 4 weeks to 18.7 years). MAIN OUTCOME MEASURES--Chamber areas, fractional area change, midwall circumferential shortening normalised to body weight. RESULTS--In the controls normalised reference values were: end diastolic cavity area, 1.47 (0.25) cm2/kg0.65; fractional area change, 0.56 (0.03); end diastolic myocardial area, 1.62 (0.25) cm2/kg0.55; midwall circumferential shortening, 0.21 (0.03). By comparison, the patients had normal chamber areas (end diastolic myocardial area, 1.57 (0.42) cm2/kg0.65), increased fractional area change, 0.68 (0.05) (P < 0.001), and normal midwall circumferential shortening, 0.21 (0.03). There was a significant relation between the degree of hypertrophy (in terms of end diastolic myocardial area) and pump function while midwall shortening remained constant: 0.08 x end diastolic myocardial area + 0.44 (r = 0.74, P < 0.001). CONCLUSIONS--The relation between myocardial shortening, wall thickness, and fractional area change emphasises that the augmentation of pump function variables in left ventricular hypertrophy in young people is an effect of the thickened wall and not necessarily due to increased myocardial shortening. This relation offers the possibility of assessing the adequacy of chamber performance with respect to the degree of hypertrophy.     

Hyperhomocysteinemia in patients with heart failure referred for cardiac transplantation: preliminary observations

BACKGROUND: Hyperhomocysteinemia is becoming recognized as a risk factor for cardiovascular disease, yet there are limited data on the prevalence of hyperhomocysteinemia in patients with heart failure. HYPOTHESIS: The purpose of this study was to examine the prevalence of hyperhomocysteinemia in patients with severe heart failure and to correlate serum homocysteine levels with factors that may affect homocysteine metabolism. METHODS: Serum homocysteine levels were measured at the time of cardiac transplant evaluation in 89 consecutive patients with severe heart failure. Homocysteine levels for patients with ischemic cardiomyopathy (ICM) were compared with levels obtained in patients with nonischemic cardiomyopathy (NICM), and homocysteine levels were correlated with demographic and hemodynamic parameters as well as functional status. RESULTS: The mean plasma homocysteine level was increased (14.3 +/- 5.3 micromol/l, normal <9.0 micromol/l) and was equivalent between patients with ICM versus NICM (14.7 +/- 5.8 micromol/l vs. 13.8 +/- 4.5 micromol/l, p = 0.44). Elevated homocysteine levels were seen in a large proportion (89%) of patients and were equally common to patients with NICM (94%) and ICM (85%). Serum homocysteine levels correlated with serum creatinine (r = 0.51, p < 0.001), with a history of diabetes (p = 0.028), and with a history of peripheral vascular disease (p = 0.045). Only 6% of patients were receiving folic acid therapy at the time of transplant referral. CONCLUSION: Hyperhomocysteinemia is common in patients with severe heart failure, and plasma homocysteine levels are uniformly elevated regardless of the etiology of heart failure. Elevated plasma homocysteine levels are likely a consequence of heart failure-related renal insufficiency.     

Medial patellofemoral ligament reconstruction in patellar instability

Background:

Medial patellofemoral ligament (MPFL) is one of the major static medial stabilising structures of the patella. MPFL is most often damaged in patients with patellar instability. Reconstruction of MPFL is becoming a common surgical procedure in treating patellar instability. We hypothesised that MPFL reconstruction was adequate to treat patients with patellar instability if the tibial tubercle and the centre of the trochlear groove (TT-TG) value was less than 20 mm and without a dysplastic trochlea.

Materials and Methods:

30 patients matching our inclusion criteria and operated between April 2009 and May 2011 were included in the study. MPFL reconstruction was performed using gracilis tendon fixed with endobutton on the patellar side and bio absorbable interference screw or staple on the femoral side. Patients were followed up with subjective criteria, Kujala score and Lysholm score.

Results:

The mean duration of followup was 25 months (range 14-38 months). The mean preoperative Kujala score was 47.5 and Lysholm score was 44.7. The mean postoperative Kujala score was 87 and Lysholm score was 88.06. None of the patients had redislocation.

Conclusion:

MPFL reconstruction using gracilis tendon gives excellent results in patients with patellar instability with no redislocations. Some patients may have persistence of apprehension.