Behavioural phenotype of SYNGAP1-related intellectual disability.

BACKGROUND: SYNGAP1- related intellectual disability (SYNGAP1-ID) is a rare genetic disorder presenting with intellectual disability (ID), epilepsy, maladaptive behaviours and communication challenges. To date, few studies have assessed the context in which these maladaptive behaviours occur. This study aims to investigate the prevalence of problem behaviours, characterise the behavioural phenotype and use well-validated measures to explore variables that maintain the behaviours. METHODS: Our sample includes 19 individuals diagnosed with SYNGAP1-ID and their parents. Parents provided information on behaviours that their children engage in, as well as their general behavioural dispositions. Well-validated measures (e.g., the Repetitive Behaviour Scale-Revised, Sensory Profile-2 and Vineland Adaptive Behaviour Scale) were used. A subset of individuals underwent further direct experimental assessment of their problem behaviour to identify the variables maintaining those problem behaviours. Parental reports were analysed using nonparametric statistical analysis; the direct assessments of individuals' problem behaviour were analysed using visual analysis and validated supplemental measures. RESULTS: All 19 individuals engaged in some form of maladaptive problem behaviour. Ratings of ritualistic, sameness and restricted behaviours measured by the RBS-R were commensurate with individuals diagnosed with idiopathic autism spectrum disorder (ASD) while self-injurious behaviours were endorsed at a higher level in SYNGAP1-ID when compared with idiopathic ASD. The problem behaviours in our cohort of patients with SYNGAP1-ID were maintained by automatic reinforcement and social attention and are positively correlated with atypical sensory responses. CONCLUSIONS: Individuals with SYNGAP1-ID engage in problem behaviours commensurate with other populations (e.g., those with ASD), they exhibit atypical response to sensory stimuli. Problem behaviours were frequently maintained by automatic reinforcement, which may result from a dysregulated sensory system. Children with SYNGAP1-ID may benefit from strategies used in persons with ASD.

Pickleball Primer: An Overview of Common Injuries, Treatment, and Optimization Strategies in Pickleball Athlete.

Pickleball is one of the fastest growing sports in the United States with millions of players nationwide. It is a relatively appealing sport because of its ease of access, low impact, and highly social atmosphere, allowing players of all ages to participate. As the number of players continues its dramatic increase, player injuries are certain to increase in turn. There is little to no orthopaedic research on pickleball-related injuries and a paucity of data regarding treatment and prevention strategies. This summary was designed to familiarize orthopaedic surgeons with the basics of the sport and highlight potential pickleball-related injuries they may encounter in practice.

Using strain to uncover the interplay between two- and three-dimensional charge density waves in high-temperature superconducting YBa2Cu3Oy.

Uniaxial pressure provides an efficient approach to control charge density waves in YBa2Cu3Oy. It can enhance the correlation volume of ubiquitous short-range two-dimensional charge-density-wave correlations, and induces a long-range three-dimensional charge density wave, otherwise only accessible at large magnetic fields. Here, we use x-ray diffraction to study the strain dependence of these charge density waves and uncover direct evidence for a form of competition between them. We show that this interplay is qualitatively described by including strain effects in a nonlinear sigma model of competing superconducting and charge-density-wave orders. Our analysis suggests that strain stabilizes the 3D charge density wave in the regions between disorder-pinned domains of 2D charge density waves, and that the two orders compete at the boundaries of these domains. No signatures of discommensurations nor of pair density waves are observed. From a broader perspective, our results underscore the potential of strain tuning as a powerful tool for probing competing orders in quantum materials.

Designing the stripe-ordered cuprate phase diagram through uniaxial-stress.

The ability to efficiently control charge and spin in the cuprate high-temperature superconductors is crucial for fundamental research and underpins technological development. Here, we explore the tunability of magnetism, superconductivity, and crystal structure in the stripe phase of the cuprate La[Formula: see text]Ba[Formula: see text]CuO[Formula: see text], with [Formula: see text] = 0.115 and 0.135, by employing temperature-dependent (down to 400 mK) muon-spin rotation and AC susceptibility, as well as X-ray scattering experiments under compressive uniaxial stress in the CuO[Formula: see text] plane. A sixfold increase of the three-dimensional (3D) superconducting critical temperature [Formula: see text] and a full recovery of the 3D phase coherence is observed in both samples with the application of extremely low uniaxial stress of [Formula: see text]0.1 GPa. This finding demonstrates the removal of the well-known 1/8-anomaly of cuprates by uniaxial stress. On the other hand, the spin-stripe order temperature as well as the magnetic fraction at 400 mK show only a modest decrease under stress. Moreover, the onset temperatures of 3D superconductivity and spin-stripe order are very similar in the large stress regime. However, strain produces an inhomogeneous suppression of the spin-stripe order at elevated temperatures. Namely, a substantial decrease of the magnetic volume fraction and a full suppression of the low-temperature tetragonal structure is found under stress, which is a necessary condition for the development of the 3D superconducting phase with optimal [Formula: see text]. Our results evidence a remarkable cooperation between the long-range static spin-stripe order and the underlying crystalline order with the three-dimensional fully coherent superconductivity. Overall, these results suggest that the stripe- and the SC order may have a common physical mechanism.

Giant lattice softening at a Lifshitz transition in Sr2RuO4.

The interplay of electronic and structural degrees of freedom in solids is a topic of intense research. More than 60 years ago, Lifshitz discussed a counterintuitive possibility: lattice softening driven by conduction electrons at topological Fermi surface transitions. The effect that he predicted, however, was small and has not been convincingly observed. Using a piezo-based uniaxial pressure cell to tune the ultraclean metal strontium ruthenate while measuring the stress-strain relationship, we reveal a huge softening of the Young's modulus at a Lifshitz transition of a two-dimensional Fermi surface and show that it is indeed driven entirely by the conduction electrons of the relevant energy band.

Repair of Chronic Patellar Tendon Rupture with Extensor Mechanism Allograft Augmentation.

The purpose of this study was to evaluate the effectiveness of our novel chronic patellar tendon repair with allograft augmentation in an active-duty military population. From 2014 to 2018, five patients with chronic patellar tendon ruptures were treated with a primary repair of the patellar tendon augmented with Achilles tendon allograft. All patients were followed for 12 months, and their range of motion, Lysholm scores, and straight leg raise ability were assessed. Additionally, their return to active military duty was followed. All patients were managed with tendon reapproximation and Achilles allograft augmentation. Lysholm scores improved in all patients from an average of 35 to 87 postoperatively. No patients demonstrated postoperative extensor lag, and patients regained an average flexion of 130 degrees. All patients returned to active military duty. We presented a safe and effective technique to manage chronic patellar tendon ruptures that produced good outcomes. (Journal of Surgical Orthopaedic Advances 32(3):242-245, 2023).

Charge Density Waves in YBa_{2}Cu_{3}O_{6.67} Probed by Resonant X-Ray Scattering under Uniaxial Compression.

We report a comprehensive Cu L_{3}-edge resonant x-ray scattering (RXS) study of two- and three-dimensional (2D and 3D) incommensurate charge correlations in single crystals of the underdoped high-temperature superconductor YBa_{2}Cu_{3}O_{6.67} under uniaxial compression up to 1% along the two inequivalent Cu─O─Cu bond directions (a and b) in the CuO_{2} planes. We confirm the strong in-plane anisotropy of the 2D charge correlations and observe their symmetric response to pressure: pressure along a enhances correlations along b, and vice versa. Our results imply that the underlying order parameter is uniaxial. In contrast, 3D long-range charge order is only observed along b in response to compression along a. Spectroscopic RXS measurements show that the 3D charge order resides exclusively in the CuO_{2} planes and may thus be generic to the cuprates. We discuss implications of these results for models of electronic nematicity and for the interplay between charge order and superconductivity.

Heat-capacity measurements under uniaxial pressure using a piezo-driven device.

We report the development of a technique to measure heat capacity at large uniaxial pressure using a piezoelectric-driven device generating compressive and tensile strain in the sample. Our setup is optimized for temperatures ranging from 8 K down to millikelvin. Using an AC heat-capacity technique, we are able to achieve an extremely high resolution and to probe a homogeneously strained part of the sample. We demonstrate the capabilities of our setup on the unconventional superconductor Sr2RuO4. By replacing thermometer and adjusting the remaining setup accordingly, the temperature regime of the experiment can be adapted to other temperature ranges of interest.

Using Uniaxial Stress to Probe the Relationship between Competing Superconducting States in a Cuprate with Spin-stripe Order.

We report muon spin rotation and magnetic susceptibility experiments on in-plane stress effects on the static spin-stripe order and superconductivity in the cuprate system La_{2-x}Ba_{x}CuO_{4} with x=0.115. An extremely low uniaxial stress of ∼0.1 GPa induces a substantial decrease in the magnetic volume fraction and a dramatic rise in the onset of 3D superconductivity, from ∼10 to 32 K; however, the onset of at-least-2D superconductivity is much less sensitive to stress. These results show not only that large-volume-fraction spin-stripe order is anticorrelated with 3D superconducting coherence but also that these states are energetically very finely balanced. Moreover, the onset temperatures of 3D superconductivity and spin-stripe order are very similar in the large stress regime. These results strongly suggest a similar pairing mechanism for spin-stripe order and the spatially modulated 2D and uniform 3D superconducting orders, imposing an important constraint on theoretical models.

Endometriosis and the microbiome: a systematic review.

BACKGROUND: The aetiology and pathogenesis of endometriosis are still under investigation. There is evidence that there is a complex bidirectional interaction between endometriosis and the microbiome. OBJECTIVE: To systematically review the available literature on the endometriosis-microbiome interaction, with the aim of guiding future inquiries in this emerging area of endometriosis research. SEARCH STRATEGY: MEDLINE, Embase, Scopus and Web of Science were searched through May 2019. A manual search of reference lists of relevant studies was also performed. SELECTION CRITERIA: Published and unpublished literature in any language describing a comparison of the microbiome state in mammalian hosts with and without endometriosis. DATA COLLECTION AND ANALYSIS: Identified studies were screened and assessed independently by two authors. Data were extracted and compiled in a qualitative synthesis of the evidence. MAIN RESULTS: Endometriosis appears to be associated with an increased presence of Proteobacteria, Enterobacteriaceae, Streptococcus spp. and Escherichia coli across various microbiome sites. The phylum Firmicutes and the genus Gardnerella also appear to have an association; however, this remains unclear. CONCLUSIONS: The complex bidirectional relationship between the microbiome and endometriosis has begun to be characterised by the studies highlighted in this systematic review. Laboratory and clinical studies demonstrate that there are indeed differences in the microbiome composition of hosts with and without endometriosis. TWEETABLE ABSTRACT: Review findings show endometriosis associated with increased Proteobacteria, Enterobacteriaceae, Streptococcus and Escherichia coli across various microbiome sites.

Constraints on the superconducting order parameter in Sr2RuO4 from oxygen-17 nuclear magnetic resonance.

Phases of matter are usually identified through spontaneous symmetry breaking, especially regarding unconventional superconductivity and the interactions from which it originates. In that context, the superconducting state of the quasi-two-dimensional and strongly correlated perovskite Sr2RuO4 is considered to be the only solid-state analogue to the superfluid 3He-A phase1,2, with an odd-parity order parameter that is unidirectional in spin space for all electron momenta and breaks time-reversal symmetry. This characterization was recently called into question by a search for an expected 'split' transition in a Sr2RuO4 crystal under in-plane uniaxial pressure, which failed to find any such evidence; instead, a dramatic rise and a peak in a single-transition temperature were observed3,4. Here we use nuclear magnetic resonance (NMR) spectroscopy of oxygen-17, which is directly sensitive to the order parameter via hyperfine coupling to the electronic spin degrees of freedom, to probe the nature of superconductivity in Sr2RuO4 and its evolution under strain. A reduction of the Knight shift is observed for all strain values and at temperatures below the critical temperature, consistent with a drop in spin polarization in the superconducting state. In unstrained samples, our results contradict a body of previous NMR work reporting no change in the Knight shift5 and the most prevalent theoretical interpretation of the order parameter as a chiral p-wave state. Sr2RuO4 is an extremely clean layered perovskite and its superconductivity emerges from a strongly correlated Fermi liquid, and our work imposes tight constraints on the order parameter symmetry of this archetypal system.

Uniaxial pressure control of competing orders in a high-temperature superconductor.

Cuprates exhibit antiferromagnetic, charge density wave (CDW), and high-temperature superconducting ground states that can be tuned by means of doping and external magnetic fields. However, disorder generated by these tuning methods complicates the interpretation of such experiments. Here, we report a high-resolution inelastic x-ray scattering study of the high-temperature superconductor YBa2Cu3O6.67 under uniaxial stress, and we show that a three-dimensional long-range-ordered CDW state can be induced through pressure along the a axis, in the absence of magnetic fields. A pronounced softening of an optical phonon mode is associated with the CDW transition. The amplitude of the CDW is suppressed below the superconducting transition temperature, indicating competition with superconductivity. The results provide insights into the normal-state properties of cuprates and illustrate the potential of uniaxial-pressure control of competing orders in quantum materials.

Gardner Transition in Physical Dimensions.

The Gardner transition is the transition that at mean-field level separates a stable glass phase from a marginally stable phase. This transition has similarities with the de Almeida-Thouless transition of spin glasses. We have studied a well-understood problem, that of disks moving in a narrow channel, which shows many features usually associated with the Gardner transition. We show that some of these features are artifacts that arise when a disk escapes its local cage during the quench to higher densities. There is evidence that the Gardner transition becomes an avoided transition, in that the correlation length becomes quite large, of order 15 particle diameters, even in our quasi-one-dimensional system.

Resistivity in the Vicinity of a van Hove Singularity: Sr_{2}RuO_{4} under Uniaxial Pressure.

We report the results of a combined study of the normal-state resistivity and superconducting transition temperature T_{c} of the unconventional superconductor Sr_{2}RuO_{4} under uniaxial pressure. There is strong evidence that, as well as driving T_{c} through a maximum at ∼3.5 K, compressive strains ϵ of nearly 1% along the crystallographic [100] axis drive the γ Fermi surface sheet through a van Hove singularity, changing the temperature dependence of the resistivity from T^{2} above, and below the transition region to T^{1.5} within it. This occurs in extremely pure single-crystals in which the impurity contribution to the resistivity is <100 nΩ cm, so our study also highlights the potential of uniaxial pressure as a more general probe of this class of physics in clean systems.

Heterogeneity of studies in anesthesiology systematic reviews: a meta-epidemiological review and proposal for evidence mapping.

Heterogeneity among the primary studies included in a systematic review (SR) is one of the most challenging considerations for systematic reviewers. Current practices in anaesthesiology SRs have not been evaluated, but traditional methods may not provide sufficient information to evaluate the true nature of these differences. We address these issues by examining the practices for evaluating heterogeneity in anesthesiology reviews. Also, we propose a mapping method for presenting heterogeneous aspects of the primary studies in SRs.We evaluated heterogeneity practices reported in SRs published in highly ranked anesthesiology journals and Cochrane reviews. Elements extracted from the SRs included heterogeneity tests, models used, analyses conducted, plots used, and I2 values. Additionally, we selected a SR to develop an evidence map in order to display clinical heterogeneity.Our statistical analysis showed 150/207 SRs reporting a test for statistical heterogeneity. Plots were used in 138 reviews to display heterogeneity. Subgroup analyses were the most commonly reported analysis (54%). Meta-regression and sensitivity analyses were used sparingly (25%; 23% respectively). A random effects model was most commonly reported (33%). Heterogeneity statistics across meta-analyses suggested that, in our sample, the majority (55%) did not present sufficient heterogeneity to be of great concern. Cochrane reviews (n=58) were also analysed. Plots were used in 88% of Cochrane reviews. Subgroup analysis was used in 59% Cochrane reviews, while sensitivity analysis was used in 62%.Many reviews did not provide sufficient detail regarding heterogeneity. We are calling for improvement to reporting practices.

Creation of a novel risk score for surgical site infection and occurrence after ventral hernia repair.

BACKGROUND: Complex ventral hernia repair (VHR) is a common surgical operation but carries a risk of complications from surgical site infections (SSI) and occurrences (SSO). We aimed to create a predictive risk score to identify patients at increased risk for SSO or SSI within 30 days of surgery. METHODS: Data were prospectively collected on all patients undergoing VHR between January 2008 and February 2015 by a single surgeon. Multivariable logistic regression was used to identify independent factors predictive of SSO and SSI. Significant predictors of SSO and SSI were assigned point values based on their odds ratios to create a novel risk score, the Hopkins ventral hernia repair SSO/SSI risk score; predicted and actual rates of outcomes were then compared using weighted regression. RESULTS: During the study period, 362 patients underwent open VHR. Thirty-day SSO and SSI occurred in 18.5 and 10% of patients, respectively. After risk adjustment, ASA class ≥3 (1 point), operative time ≥4 h (2 points), and the absence of a postoperative wound vacuum dressing (1 point) were predictive of 30-day SSO. Predicted risk of SSO utilizing this scoring system was 9.7, 19.4, 29.1, and 38.8% for 1, 2, 3, and 4 points (AUC = 0.73). For SSI, operative time ≥4 h (1 point) and the lack of a wound vacuum dressing (1 point) were predictive. Predicted risk of SSI based on this scoring system was 12.5% for 1 point and 25% for 2 points (AUC = 0.71). Actual vs. predicted rates of SSO and SSI correlated strongly for risk model with a coefficient of determination (R 2) of 0.92 and 0.91, respectively. CONCLUSION: The novel Hopkins ventral hernia repair risk score accurately predicts risk of SSO and SSI after complex VHR. Further studies using a prospective randomized controlled trial will be needed to further validate our findings.

Effect of hernia size on operative repair and post-operative outcomes after open ventral hernia repair.

BACKGROUND: Ventral hernia repair (VHR) is a commonly performed operation, but analysis of patient outcomes based upon hernia size is lacking. We sought to identify differences in operative repair and post-operative morbidity and mortality after open VHR based on hernia defect size. METHODS: Patient and operative data were retrospectively reviewed on all patients undergoing open incisional VHR between January 2008 and February 2015 by a single surgeon at the Johns Hopkins Hospital. Patient variables were described by means for continuous variables and percentages for discrete variables, with differences between groups calculated by Chi-squared analysis. RESULTS: During the study period, 228 patients underwent open VHR during which intraoperative defect size was measured. Patients were split into four groups based upon defect size: less than 200 cm2, 200-300 cm2, 301-400 cm2, and over 400 cm2. Patients with large defects were more likely to present with a recurrent hernia (P = 0.007) and trended towards a history of wound infections (P = 0.07). Operative time was significantly longer as defect size increased (P < 0.001). Component separation was most frequently used in patients with defects 200-300 cm2 in size (P = 0.001), in whom primary closure was most likely to occur. While mesh was used in almost all patients, the specific location (overlay only, underlay only, or overlay with underlay) depended on hernia size (P < 0.001). Mean length of stay increased with defect size (P < 0.001). Larger defect size was associated with increased 30-day morbidity (P = 0.03) but not readmission (P = 0.53), recurrence (P = 0.99), or mortality (P = 0.99). CONCLUSION: Hernia defect size affects operative time and surgical technique for repair of a ventral hernia. Larger defect size is associated with increased post-operative morbidity and length of stay but not readmission, recurrence, or mortality. Hernia size greater than 400 cm2 should not be a limitation to operative repair.

Long-term, high-level hepatic secretion of acid α-glucosidase for Pompe disease achieved in non-human primates using helper-dependent adenovirus.

Pompe disease (glycogen storage disease type II (GSD-II)) is a myopathy caused by a genetic deficiency of acid α-glucosidase (GAA) leading to lysosomal glycogen accumulation causing muscle weakness, respiratory insufficiency and death. We previously demonstrated in GSD-II mice that a single injection of a helper-dependent adenovirus (HD-Ad) expressing GAA resulted in at least 300 days of liver secretion of GAA, correction of the glycogen storage in cardiac and skeletal muscles and improved muscle strength. Recent reports suggest that gene therapy modeling for lysososomal storage diseases in mice fails to predict outcomes in larger animal models. We therefore evaluated an HD-Ad expressing GAA in non-human primates. The baboons not only tolerated the procedure well, but the results also confirmed that a single dose of the HD-Ad allowed the livers of the treated animals to express and secrete large amounts of GAA for at least 6 months, at levels similar to those achieved in mice. Moreover, we detected liver-derived GAA in the heart, diaphragm and skeletal muscles of the treated animals for the duration of the study at levels that corrected glycogen accumulation in mice. This work validates our proof-of-concept studies in mice, and justifies future efforts using Ad-based vectors in Pompe disease patients.

Analysis of risk factors and prevalence of haemoplasma infection in dogs.

Mycoplasma haemocanis (Mhc) and 'Candidatus Mycoplasma haematoparvum' (CMhp) are canine haemoplasma species that can induce anaemia in immunocompromised and/or splenectomised dogs. This study aimed to determine the prevalence and phylogeny of canine haemoplasma species in dogs from Nigeria and describe any risk factors for infection. Canine haemoplasma species-specific and generic haemoplasma qPCR assays were used. The species-specific qPCR assays found Mhc infection in 18 of 245 dogs (7.3%), and CMhp infection in only one dog (0.4%). The generic haemoplasma qPCR assays were positive in 44 of 245 (17.9%) dogs. Twenty-five dogs had discordant qPCR results in that they were generic haemoplasma qPCR positive but species-specific qPCR negative. Further evaluation of these dogs by 16S rDNA sequencing gave limited results but 5 were confirmed to be infected with non-haemoplasma species: 2 Anaplasma phagocytophilum, 1 Anaplasma ovis, 1 Serratia marcescens and 1 Aerococcus spp. The 16S rRNA gene sequences from Mhc species showed>99.8% identity with each other and>99.6% identity with GenBank sequences, and resided in a single clade with other global Mhc and Mycoplasma haemofelis sequences, indicating low 16S rRNA genetic variability amongst this canine haemoplasma species.

Outcomes of Endovascular Aortic Aneurysm Repair in Kidney Transplant Recipients: Results From a National Quality Initiative.

Contrast-induced nephropathy after endovascular aortic aneurysm repair (EVAR) in kidney transplant recipients (KTRs) can have devastating consequences. The Vascular Quality Initiative (VQI) database was queried to select all KTRs who underwent EVAR between January 2003 and December 2014. Our primary outcome was renal dysfunction, defined as acute kidney injury (AKI; elevation of serum creatinine >0.5 mg/dL from baseline) or new postoperative hemodialysis requirement. Within the EVAR VQI dataset, 40 patients were KTRs (40 of 17 213, or 0.2%). Renal dysfunction occurred in five of 40 patients in the KTR group in comparison to 779 of 17 173 patients in the nontransplanted group (12.5% versus 4.5%, p < 0.01). Emergent EVAR was required in 2 (5%) patients, one of whom required dialysis after surgery and subsequently died. One-year survival after EVAR was similar in the two groups (92.9% versus 93.1%, p = 0.73). KTRs who developed renal dysfunction had significantly lower preoperative estimated glomerular filtration rates (eGFRs) (29.5 versus 54.7, p = 0.007) and a significantly higher iodine:eGFR ratio (0.78 versus 0.39, p = 0.02) despite receiving a similar volume of contrast (70.0 versus 68.8, p = 0.97). Renal dysfunction is 3 times more frequent in KTRs treated with EVAR, though overall survival did not differ between the groups. Decreased preoperative eGFR and a higher iodine:eGFR ratio are associated with postoperative renal dysfunction.