Highly Cross-Linked Polyethylene in Patients 50 Years of Age and Younger: A 20-year Follow-Up Analysis.

BACKGROUND: Highly cross-linked polyethylene (HXLPE) has been an excellent bearing for total hip arthroplasty (THA) due to improved wear characteristics compared to conventional materials. Patients 50 years of age or younger are at high risk for wear-related complications of their THA, and few studies have followed these patients who have HXPLE into the third decade. METHODS: In a retrospective review of 88 consecutive THAs performed in 77 patients aged 50 years and younger (mean 41; range, 20 to 50), in which HXLPE was utilized, they were evaluated for their clinical and radiographic results at an average of 20-year follow-up (range, 18 to 24). The current study reports on longer-term follow-up from our previously published series at shorter follow-up times. Patients were categorized by femoral head material: cobalt chrome (n = 14), ceramic (n = 30), and oxidized zirconium (n = 22) and by femoral head size: 26 mm (n = 12), 28 mm (n = 46), and 32 mm (n = 8). Harris Hip Scores were collected preoperatively and at the most recent follow-up. Radiographs were evaluated for linear and volumetric wear, radiolucent lines, and osteolysis. RESULTS: Mean Harris Hip Scores improved from 47.1 (standard deviation [SD] 8.8) preoperatively to 92.0 (SD 7.7) (P < .0001) at 20-year follow-up. There was one hip that was revised for recurrent instability, and no hip demonstrated radiographic evidence of loosening or osteolysis. The mean polyethylene linear wear rate was 0.017 (SD 0.012) mm/y, and the mean polyethylene volumetric wear rate was 3.15 (SD 2.8) mm3/year, with no significant differences based on articulation type or head size. CONCLUSIONS: Total hip arthroplasty with HXLPE in patients ≤ 50 years of age continues to demonstrate excellent long-term clinical and radiographic outcomes with low wear characteristics at 20-year follow-up, regardless of femoral head material or size.

Novel Technique for the Identification of Hip Implants Using Artificial Intelligence.

BACKGROUND: The anticipated growth of total hip arthroplasty will result in an increased need for revision total hip arthroplasty. Preoperative planning, including identifying current implants, is critical for successful revision surgery. Artificial intelligence (AI) is promising for aiding clinical decision-making, including hip implant identification. However, previous studies have limitations such as small datasets, dissimilar stem designs, limited scalability, and the need for AI expertise. To address these limitations, we developed a novel technique to generate large datasets, tested radiographically similar stems, and demonstrated scalability utilizing a no-code machine learning solution. METHODS: We trained, validated, and tested an automated machine learning-implemented convolutional neural network to classify 9 radiographically similar femoral implants with a metaphyseal-fitting wedge taper design. Our novel technique uses computed tomography-derived projections of a 3-dimensional scanned implant model superimposed within a computed tomography pelvis volume. We employed computer-aided design modeling and MATLAB to process and manipulate the images. This generated 27,020 images for training (22,957) and validation (4,063) sets. We obtained 786 test images from various sources. The performance of the model was evaluated by calculating sensitivity, specificity, and accuracy. RESULTS: Our machine learning model discriminated the 9 implant models with a mean accuracy of 97.4%, sensitivity of 88.4%, and specificity of 98.5%. CONCLUSIONS: Our novel hip implant detection technique accurately identified 9 radiographically similar implants. The method generates large datasets, is scalable, and can include historic or obscure implants. The no-code machine learning model demonstrates the feasibility of obtaining meaningful results without AI expertise, encouraging further research in this area.

Metaphyseal Fixation Using Cones and Sleeves for Severe Proximal Tibial Bone Loss.

BACKGROUND: Tibial bone defects are commonly encountered in revision total knee arthroplasty (rTKA) and can be managed with metaphyseal cones or sleeves. Few studies have directly compared tibial cones and sleeves in rTKA, and none have limited this comparison to the most severe tibial defects. The purpose of this study was to evaluate and compare the outcomes of metaphyseal cones and sleeves for tibial reconstruction in rTKA regarding implant fixation and clinical outcomes. METHODS: A retrospective review was conducted on patients undergoing rTKA in which metaphyseal cones or sleeves were utilized for addressing metaphyseal bone loss (34 cones and 18 sleeves). Tibial bone loss was classified according to the Anderson Orthopaedic Research Institute bone defect classification, with types 2B and 3 being included. Patient-reported outcomes and postoperative complications were collected, and a radiographic evaluation of osseointegration or loosening was performed. RESULTS: There were 52 knees included (34 cones, 18 sleeves), with a median follow-up of 41.0 months. All-cause implant survival was 100% at 2 years and 96% (95% confidence interval: 76 to 99%) at 4 years, with 98% of tibial components demonstrating osseointegration at the final follow-up. During follow-up, there were a total 11 revisions, of which 1 sleeve was revised secondary to implant loosening. Tibial sleeves had a higher risk of revision compared to tibial cones (P < .01), and sleeves fixed with a hybrid technique were more likely to need revision than cones fixed by the same method (P = .01). CONCLUSIONS: Porous metaphyseal tibial cones and tibial metaphyseal sleeves both performed well at a 41-month median follow-up with no difference in aseptic survivorship between the 2 constructs. Both demonstrate high rates of osseointegration, low rates of aseptic failure, and significant improvement in Knee Society Scores in patients with severe tibial defects in rTKA.

In-Hospital Mortality and Related Outcomes for Elevated Risk Acute Pulmonary Embolism Treated With Mechanical Thrombectomy Versus Routine Care.

PURPOSE: To compare in-hospital mortality and other hospitalization related outcomes of elevated risk patients (Pulmonary Embolism Severity Index [PESI] score of 4 or 5, and, European Society of Cardiology [ESC] classification of intermediate-high or high risk) with acute central pulmonary embolism (PE) treated with mechanical thrombectomy (MT) using the Inari FlowTriever device versus those treated with routine care (RC). MATERIALS AND METHODS: Retrospective data was collected of all patients with acute, central PE treated at a single institution over 2 concurrent 18-month periods. All collected patients were risk stratified using the PESI and ESC Guidelines. The comparison was made between patients with acute PE with PESI scores of 4 or 5, and, ESC classification of intermediate-high or high risk based on treatment type: MT and RC. The primary endpoint evaluated was in-hospital mortality. Secondary endpoints included intensive care unit (ICU) length of stay, total hospital length of stay, and 30-day readmission. RESULTS: Fifty-eight patients met inclusion criteria, 28 in the MT group and 30 in the RC group. Most RC patients were treated with systemic anticoagulation alone (24 of 30). In-hospital mortality was significantly lower for the MT group than for the RC group (3.6% vs 23.3%, P < .05), as was the average ICU length of stay (2.1 ± 1.2 vs 6.1 ± 8.6 days, P < .05). Total hospital length of stay and 30-day readmission rates were similar between MT and RC groups. CONCLUSION: Initial retrospective comparison suggests MT can improve in-hospital mortality and decrease ICU length of stay for patients with acute, central PE of elevated risk (PESI 4 or 5, and, ESC intermediate-high or high risk).

Interferon-Induced Protein 44 and Interferon-Induced Protein 44-Like Restrict Replication of Respiratory Syncytial Virus.

Cellular intrinsic immunity, mediated by the expression of an array of interferon-stimulated antiviral genes, is a vital part of host defense. We have previously used a bioinformatic screen to identify two interferon-stimulated genes (ISG) with poorly characterized function, interferon-induced protein 44 (IFI44) and interferon-induced protein 44-like (IFI44L), as potentially being important in respiratory syncytial virus (RSV) infection. Using overexpression systems, CRISPR-Cas9-mediated knockout, and a knockout mouse model, we investigated the antiviral capability of these genes in the control of RSV replication. Overexpression of IFI44 or IFI44L was sufficient to restrict RSV infection at an early time postinfection. Knocking out these genes in mammalian airway epithelial cells increased levels of infection. Both genes express antiproliferative factors that have no effect on RSV attachment but reduce RSV replication in a minigenome assay. The loss of Ifi44 was associated with a more severe infection phenotype in a mouse model of infection. These studies demonstrate a function for IFI44 and IFI44L in controlling RSV infection.IMPORTANCE RSV infects all children under 2 years of age, but only a subset of children get severe disease. We hypothesize that susceptibility to severe RSV necessitating hospitalization in children without predefined risk factors is, in part, mediated at the antiviral gene level. However, there is a large array of antiviral genes, particularly in the ISG family, the mechanism of which is poorly understood. Having previously identified IFI44 and IFI44L as possible genes of interest in a bioinformatic screen, we dissected the function of these two genes in the control of RSV. Through a range of overexpression and knockout studies, we show that the genes are antiviral and antiproliferative. This study is important because IFI44 and IFI44L are upregulated after a wide range of viral infections, and IFI44L can serve as a diagnostic biomarker of viral infection.

Room Temperature Terahertz Electroabsorption Modulation by Excitons in Monolayer Transition Metal Dichalcogenides.

The interaction between off-resonant laser pulses and excitons in monolayer transition metal dichalcogenides is attracting increasing interest as a route for the valley-selective coherent control of the exciton properties. Here, we extend the classification of the known off-resonant phenomena by unveiling the impact of a strong THz field on the excitonic resonances of monolayer MoS2. We observe that the THz pump pulse causes a selective modification of the coherence lifetime of the excitons, while keeping their oscillator strength and peak energy unchanged. We rationalize these results theoretically by invoking a hitherto unobserved manifestation of the Franz-Keldysh effect on an exciton resonance. As the modulation depth of the optical absorption reaches values as large as 0.05 dB/nm at room temperature, our findings open the way to the use of semiconducting transition metal dichalcogenides as compact and efficient platforms for high-speed electroabsorption devices.

The cause of death in bacterial meningitis.

BACKGROUND: Death from bacterial meningitis is rarely attributed to the actual event causing death. The present study therefore categorized and characterized the cause and time of death due to bacterial meningitis. METHODS: In a cohort of patients > 15 years of age with community acquired bacterial meningitis the medical records were reviewed, and a clinical cause of death categorized into six main categories: 1) CNS complications, 2) Systemic complications, 3) Combination of systemic and CNS complications, 4) Sudden death, 5) Withdrawal of care, or 6) Unknown. RESULTS: We identified 358 patients of which 84 (23%) died in-hospital. Causes of death were ascribed to CNS complications in 43%, Systemic complications in 39%, Combined CNS and systemic complications in 4%, Sudden death in 7% and withdrawal of care in 5%. Brain herniation, circulatory failure, intractable seizures and other brain injury were the most common specific causes of death within 14 days from admission (55%). CONCLUSION: Fatal complications due to the primary infection - meningitis - is most common within 14 days of admission. The diversity of complications causing death in meningitis suggest that determining the clinical cause of death is essential to the evaluation of novel treatment strategies.

Does Coronal Plane Malalignment of the Tibial Insert in Total Ankle Arthroplasty Alter Distal Foot Bone Mechanics? A Cadaveric Gait Study.

BACKGROUND: Total ankle arthroplasty (TAA) is becoming a more prevalent treatment for end-stage ankle arthritis. However, the effects of malalignment on TAA remain poorly understood. QUESTIONS/PURPOSES: The purpose of this study was to quantify the mechanical effects of coronal plane malalignment of the tibial insert in TAA using cadaveric gait simulation. Specifically, we asked, is there a change in (1) ankle joint congruency, (2) kinematic joint position, (3) kinematic ROM, (4) peak plantar pressure, and (5) center of pressure with varus and valgus malalignment? METHODS: A modified TAA was implanted into seven cadaveric foot specimens. Wedges were used to simulate coronal plane malalignment of the tibial insert. The degree of malalignment (tibial insert angle [TIA] and talar component angle [TCA]) was quantified radiographically for neutral and 5°, 10°, and 15° varus and valgus wedges. Dynamic walking at 1/6 of physiological speed was simulated using a robotic gait simulator. A motion capture system was used to measure foot kinematics, and a pressure mat was used to measure plantar pressure. Joint congruency was quantified as the difference between TIA and TCA. Continuous joint position, joint ROM, peak plantar pressure, and center of pressure for varus and valgus malalignment compared with neutral alignment were estimated using linear mixed effects regression. Pairwise comparisons between malalignment conditions and neutral were considered significant if both the omnibus test for the overall association between outcome and malalignment and the individual pairwise comparison (adjusted for multiple comparisons within a given outcome) had p ≤ 0.05. RESULTS: Descriptively, the TIA and TCA were both less pronounced than the wedge angle and component incongruence was seen (R = 0.65; p < 0.001). Varus malalignment of the tibial insert shifted the tibiotalar joint into varus and internally rotated the joint. The tibiotalar joint's ROM slightly increased as the TIA shifted into varus (1.3 ± 0.7° [mean ± SD] [95% confidence interval -0.7 to 3.4]; p = 0.03), and the first metatarsophalangeal joint's ROM decreased as the TIA shifted into varus (-1.9 ± 0.9° [95% CI -5.6 to 1.7]; p = 0.007). In the sagittal plane, the naviculocuneiform joint's ROM slightly decreased as the TIA shifted into varus (-0.9 ± 0.4° [95% CI -2.1 to 0.3]; p = 0.017). Hallux pressure increased as the TIA became more valgus (59 ± 50 kPa [95% CI -88 to 207]; p = 0.006). The peak plantar pressure slightly decreased in the third and fourth metatarsals as the TIA shifted into valgus (-15 ± 17° [95% CI -65 to 37]; p = 0.03 and -8 ± 4° [95% CI -17 to 1]; p = 0.048, respectively). The fifth metatarsal's pressure slightly decreased as the TIA shifted into valgus (-18 ± 12 kPa [95% CI -51 to 15]) or varus (-7 ± 18 kPa [95% CI -58 to 45]; p = 0.002). All comparisons were made to the neutral condition. CONCLUSIONS: In this cadaver study, coronal plane malalignment in TAA altered foot kinematics and plantar pressure. In general, varus TAA malalignment led to varus shift and internal rotation of the tibiotalar joint, a slight increase in the tibiotalar ROM, and a slight decrease in the first metatarsophalangeal ROM, while a valgus TAA malalignment was manifested primarily through increased hallux pressure with a slight off-loading of the third and fourth metatarsals. CLINICAL RELEVANCE: This study may increase our understanding of the biomechanical processes that underlie the unfavorable clinical outcomes (such as, poor patient-reported outcomes or implant loosening) that have been associated with coronal plane malalignment of the tibial component in TAA.

Terahertz-Driven Stark Spectroscopy of CdSe and CdSe-CdS Core-Shell Quantum Dots.

The effects of large external fields on semiconductor nanostructures could reveal much about field-induced shifting of electronic states and their dynamical responses and could enable electro-optic device applications that require large and rapid changes in optical properties. Studies of quasi-dc electric field modulation of quantum dot (QD) properties have been limited by electrostatic breakdown processes observed under high externally applied field levels. To circumvent this, here we apply ultrafast terahertz (THz) electric fields with switching times on the order of 1 ps. We show that a pulsed THz electric field, enhanced by a microslit field enhancement structure (FES), can strongly manipulate the optical absorption properties of a thin film of CdSe and CdSe-CdS core-shell QDs on the subpicosecond time scale with spectral shifts that span the visible to near-IR range. Numerical simulations using a semiempirical tight binding model show that the band gap of the QD film can be shifted by as much a 79 meV during these time scales. The results allow a basic understanding of the field-induced shifting of electronic levels and suggest electro-optic device applications.

Quantitative electroencephalography supports diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy.

Long-term treatment of multiple sclerosis with natalizumab (NTZ) carries the risk of a devastating complication in the form of an encephalopathy caused by a reactivation of a latent John Cunningham virus infection (progressive multifocal leucoencephalopathy, PML). Early diagnosis is associated with considerably better prognosis. Quantitative EEG as an objective, rater-independent technique provides high sensitivity (88%) and specificity (82%) for the diagnosis of NTZ-PML. Combination of diagnostic modalities addressing static morphological (brain MRI) as well as functional (EEG) pathologic changes may improve risk management programmes.

Safety and Efficacy of Acute Pulmonary Embolism Treated via Large-Bore Aspiration Mechanical Thrombectomy Using the Inari FlowTriever Device.

PURPOSE: To report initial experience with safety and efficacy in the treatment of pulmonary embolism (PE) using the FlowTriever device. MATERIALS AND METHODS: A single-center retrospective study was performed in all patients with acute central PE treated using the FlowTriever device between March 2018 and March 2019. A total of 46 patients were identified (massive = 8; submassive = 38), all with right ventricular (RV) strain and 26% with thrombolytic contraindications. Technical success (according to SIR reporting guidelines) and clinical success (defined as mean pulmonary artery pressure intraprocedural improvement) are reported, as are major device and procedure-related complications within 30 days after discharge. RESULTS: Technical success was achieved in 100% of cases (n = 46). Average mean pulmonary artery pressure improved significantly from before to after the procedure for the total population (33.9 ± 8.9 mm Hg before, 27.0 ± 9.0 mm Hg after; P < .0001; 95% confidence interval [CI], 5.0-8.8), submassive cohort (34.7 ± 9.1 mm Hg before, 27.4 ± 9.2 mm Hg after; P < .0001; 95% CI, 5.2-9.5) and massive cohort (30.4 ± 6.9 mm Hg before, 25.4 ± 8.2 mm Hg after; P < .05; 95% CI:0.4-9.6). Intraprocedural reduction in mean pulmonary artery pressure was achieved in 88% (n = 37 of 42). A total of 100% of patients (n = 46 of 46) survived to hospital discharge. In total, 71% of patients (n = 27 of 38) experienced intraprocedural reduction in supplemental oxygen requirements. Two major adverse events (4.6%) included hemoptysis requiring intubation, and procedure-related blood loss requiring transfusion. No delayed procedure-related complications or deaths occurred within 30 days of hospital discharge. CONCLUSIONS: Initial clinical experience using the FlowTriever to perform mechanical thrombectomy showed encouraging trends with respect to safety and efficacy for the treatment of acute central, massive, and submassive pulmonary embolism.

Portable standoff spectrometer for hazard identification using integrated quantum cascade laser arrays from 6.5 to 11 µm.

This article presents new spectroscopic results in standoff chemical detection that are enabled by monolithic arrays of Distributed Feedback (DFB) Quantum Cascade Lasers (QCLs), with each array element at a slightly different wavelength than its neighbor. The standoff analysis of analyte/substrate pairs requires a laser source with characteristics offered uniquely by a QCL Array. This is particularly true for time-evolving liquid chemical warfare agent (CWA) analysis. In addition to describing the QCL array source developed for long wave infrared coverage, a description of an integrated prototype standoff detection system is provided. Experimental standoff detection results using the man-portable system for droplet examination from 1.3 meters are presented using the CWAs VX and T-mustard as test cases. Finally, we consider three significant challenges to working with droplets and liquid films in standoff spectroscopy: substrate uptake of the analyte, time-dependent droplet spread of the analyte, and variable substrate contributions to retrieved signals.

Terahertz-Driven Luminescence and Colossal Stark Effect in CdSe-CdS Colloidal Quantum Dots.

Optical properties of colloidal semiconductor quantum dots (QDs), arising from quantum mechanical confinement of charge, present a versatile testbed for the study of how high electric fields affect the electronic structure of nanostructured solids. Studies of quasi-DC electric field modulation of QD properties have been limited by electrostatic breakdown processes under high externally applied electric fields, which have restricted the range of modulation of QD properties. In contrast, here we drive CdSe-CdS core-shell QD films with high-field THz-frequency electromagnetic pulses whose duration is only a few picoseconds. Surprisingly, in response to the THz excitation, we observe QD luminescence even in the absence of an external charge source. Our experiments show that QD luminescence is associated with a remarkably high and rapid modulation of the QD bandgap, which changes by more than 0.5 eV (corresponding to 25% of the unperturbed bandgap energy). We show that these colossal energy shifts can be explained by the quantum confined Stark effect even though we are far outside the regime of small field-induced shifts in electronic energy levels. Our results demonstrate a route to extreme modulation of material properties and to a compact, high-bandwidth THz detector that operates at room temperature.

Both CD8+ and CD4+ T Cells Contribute to Corneal Clouding and Viral Clearance following Vaccinia Virus Infection in C57BL/6 Mice.

UNLABELLED: Vaccinia virus (VACV) keratitis is a serious complication following smallpox vaccination and can lead to blindness. The pathological mechanisms involved in ocular VACV infection are poorly understood. Previous studies have used rabbits, but the lack of immune reagents and transgenic or knockout animals makes them less suitable for mechanistic studies. We report that infection of C57BL/6 mice with 1 × 10(7) PFU of vaccinia virus strain WR results in blepharitis, corneal neovascularization, and stromal keratitis. The DryVax strain of VACV was completely attenuated. Infection required corneal scarification and replication-competent virus, and the severity of ocular disease was similar in 4- to 6-week-old and 1-year-old mice. Viral titers peaked at approximately 1 × 10(6) PFU on day 5 postinfection, and virus had not cleared by day 13 postinfection. Neutrophils were found in the peripheral cornea on day 1 after infection and then declined, followed by infiltration of both CD4(+) and CD8(+) T cells, which remained peripheral throughout the infection. Blood vessel growth extended 2 to 5 mm into the cornea from the limbus. Infection of CD4(-/-), CD8(-/-), or antibody-depleted mice resulted in similar disease severity and corneal clouding, indicating that both T-cell subsets were involved in the immunopathological response. Depletion of both CD4(+) and CD8(+) T cells resulted in significantly more severe disease and failure to clear the virus. On the basis of our results, the pathology of VACV keratitis is significantly different from that of herpes simplex virus keratitis. Further studies are likely to reveal novel information regarding virulence and immune responses to viral ocular infection. IMPORTANCE: Potentially blinding eye infections can occur after vaccination for smallpox. Very little is known about the pathological mechanisms that are involved, and the information that is available was generated using rabbit models. The lack of immunological reagents for rabbits makes such studies difficult. We characterized a mouse model of vaccinia virus ocular disease using C57BL/6 mice and strain WR and show that both CD4(+) and CD8(+) T-cell subsets play a role in the blinding eye disease and in controlling virus replication. On the basis of these results, vaccinia virus keratitis is significantly different from herpes simplex virus keratitis, and further studies using this model should generate novel insights into immunopathological responses to viral ocular infection.

Childhood trauma is associated with increased brain responses to emotionally negative as compared with positive faces in patients with psychotic disorders.

BACKGROUND: Childhood trauma increases risk of a range of mental disorders including psychosis. Whereas the mechanisms are unclear, previous evidence has implicated atypical processing of emotions among the core cognitive models, in particular suggesting altered attentional allocation towards negative stimuli and increased negativity bias. Here, we tested the association between childhood trauma and brain activation during emotional face processing in patients diagnosed with psychosis continuum disorders. In particular, we tested if childhood trauma was associated with the differentiation in brain responses between negative and positive face stimuli. We also tested if trauma was associated with emotional ratings of negative and positive faces. METHOD: We included 101 patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM) schizophrenia spectrum or bipolar spectrum diagnosis. History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Brain activation was measured with functional magnetic resonance imaging during presentation of faces with negative or positive emotional expressions. After the scanner session, patients performed emotional ratings of the same faces. RESULTS: Higher levels of total childhood trauma were associated with stronger differentiation in brain responses to negative compared with positive faces in clusters comprising the right angular gyrus, supramarginal gyrus, middle temporal gyrus and the lateral occipital cortex (Cohen's d = 0.72-0.77). In patients with schizophrenia, childhood trauma was associated with reporting negative faces as more negative, and positive faces as less positive (Cohen's d > 0.8). CONCLUSIONS: Along with the observed negativity bias in the assessment of emotional valence of faces, our data suggest stronger differentiation in brain responses between negative and positive faces with higher levels of trauma.

Increase in migraine diagnoses and guideline-concordant treatment in veterans, 2004-2012.

Background and aim Health administrators, policy makers, and educators have attempted to increase guideline adherence of migraine medications while reducing inappropriate use of opioid- and barbiturate-containing medications. We evaluated the burden of migraine and proportion of guideline-concordant care in a large, national health care system over time. Methods We conducted a time-series study using data from the Veterans Health Administration (VHA) electronic health record. Veterans with migraines were identified by ICD-9 code (346.X). Prescriptions and comorbid conditions were evaluated before and after migraine diagnosis. Chi-square tests and logistic regression were performed. Results A total of 57,064 veterans were diagnosed with migraine headache (5.3%), with women significantly more likely diagnosed (11.6% vs. 4.4%, p < 0.0001). The number of veterans diagnosed with migraine has significantly increased over the years. By 2012, triptans were prescribed to 43% of people with migraine, with no difference by gender. However, triptan prescriptions increased from 2004 to 2012 in men, but not women, veterans. Preventive medicines showed a significant increase with the year of migraine diagnosis, after controlling for age, sex, race, and for comorbidities treated with medications used for migraine prevention. Conclusions The burden of migraines is increasing within the VHA, with a corresponding increase in the delivery of guideline-concordant acute and prophylactic migraine-specific medication.

Polyhydroxybutyrate and polyhydroxydodecanoate produced by Burkholderia contaminans IPT553.

AIMS: In this paper, we introduce a new Burkholderia contaminans capable of producing a newly characterized polymer. METHODS AND RESULTS: CG-MS and magnetic nuclear resonance 1 H and 13 C were used to determine the constitution of polymers produced in glucose, glucose with casein, sucrose and sucrose with casein. Three pairs of primers were used to find the polyhydroxyalkanoates (PHA) synthase class and sequence. The synthesized polymers were composed by short-chain length PHA (scl-PHA), especially polyhydroxybutyrate (PHB), and medium chain length PHA (mcl-PHA), especially polyhydroxydodecanoate (PHDd), and their concentration, constitution and molecular weight depend on carbon source used. The bacterium showed only class I synthase which could not explain the mcl-PHA production. CONCLUSIONS: Burkholderia contaminans has a class I PHA synthase and produces PHB combined to PHDd when cultivated in sucrose or glucose, and PHDd concentration is affected when casein is used. SIGNIFICANCE AND IMPACT OF THE STUDY: PHA are natural polymers produced by a wide range of bacteria. The presence of PHDd monomers confers to the polymer elastomeric properties. Previously, PHDd was only obtained when bacteria were cultivated in related carbon source. In this work, B. contaminansIPT553 produced PHB with PHDd using simple and low-cost carbon sources that can make possible the cheaper production of a more flexible biopolymer with crystallinity and elasticity different from the more common PHAs.

Reduced heart rate variability in schizophrenia and bipolar disorder compared to healthy controls.

OBJECTIVE: Despite current diagnostic systems distinguishing schizophrenia (SZ) and bipolar disorder (BD) as separate diseases, emerging evidence suggests they share a number of clinical and epidemiological features, such as increased cardiovascular disease (CVD) risk. It is not well understood if poor cardiac autonomic nervous system regulation, which can be indexed non-invasively by the calculation of heart rate variability (HRV), contributes to these common CVD risk factors in both diseases. METHOD: We calculated HRV in 47 patients with SZ, 33 patients with BD and 212 healthy controls. Measures of symptom severity were also collected from the patient groups. RESULTS: Heart rate variability was significantly reduced in both these disorders in comparison with the healthy participants; however, there were no HRV differences between disorders. Importantly, these reductions were independent of the medication, age or body mass index effects. There was also preliminary evidence that patients with reduced HRV had increased overall and negative psychosis symptom severity regardless of SZ or BD diagnosis. CONCLUSION: We suggest that HRV may provide a possible biomarker of CVD risk and symptom severity in severe mental illness. Thus, our results highlight the importance of cardiometabolic screening across SZ and bipolar spectrum disorders.

Design of glycoconjugate vaccines against invasive African Salmonella enterica serovar Typhimurium.

Nontyphoidal salmonellae, particularly Salmonella enterica serovar Typhimurium, are a major cause of invasive disease in Africa, affecting mainly young children and HIV-infected individuals. Glycoconjugate vaccines provide a safe and reliable strategy against invasive polysaccharide-encapsulated pathogens, and lipopolysaccharide (LPS) is a target of protective immune responses. With the aim of designing an effective vaccine against S. Typhimurium, we have synthesized different glycoconjugates, by linking O-antigen and core sugars (OAg) of LPS to the nontoxic mutant of diphtheria toxin (CRM(197)). The OAg-CRM(197) conjugates varied in (i) OAg source, with three S. Typhimurium strains used for OAg extraction, producing OAg with differences in structural specificities, (ii) OAg chain length, and (iii) OAg/CRM(197) ratio. All glycoconjugates were compared for immunogenicity and ability to induce serum bactericidal activity in mice. In vivo enhancement of bacterial clearance was assessed for a selected S. Typhimurium glycoconjugate by challenge with live Salmonella. We found that the largest anti-OAg antibody responses were elicited by (i) vaccines synthesized from OAg with the highest glucosylation levels, (ii) OAg composed of mixed- or medium-molecular-weight populations, and (iii) a lower OAg/CRM(197) ratio. In addition, we found that bactericidal activity can be influenced by S. Typhimurium OAg strain, most likely as a result of differences in OAg O-acetylation and glucosylation. Finally, we confirmed that mice immunized with the selected OAg-conjugate were protected against S. Typhimurium colonization of the spleen and liver. In conclusion, our findings indicate that differences in the design of OAg-based glycoconjugate vaccines against invasive African S. Typhimurium can have profound effects on immunogenicity and therefore optimal vaccine design requires careful consideration.

Bronchial arteries: anatomy, function, hypertrophy, and anomalies.

The two main sources of blood supply to the lungs and their supporting structures are the pulmonary and bronchial arteries. The bronchial arteries account for 1% of the cardiac output but can be recruited to provide additional systemic circulation to the lungs in various acquired and congenital thoracic disorders. An understanding of bronchial artery anatomy and function is important in the identification of bronchial artery dilatation and anomalies and the formulation of an appropriate differential diagnosis. Visualization of dilated bronchial arteries at imaging should alert the radiologist to obstructive disorders that affect the pulmonary circulation and prompt the exclusion of diseases that produce or are associated with pulmonary artery obstruction, including chronic infectious and/or inflammatory processes, chronic thromboembolic disease, and congenital anomalies of the thorax (eg, proximal interruption of the pulmonary artery). Conotruncal abnormalities, such as pulmonary atresia with ventricular septal defect, are associated with systemic pulmonary supply provided by aortic branches known as major aortopulmonary collaterals, which originate in the region of the bronchial arteries. Bronchial artery malformation is a rare left-to-right or left-to-left shunt characterized by an anomalous connection between a bronchial artery and a pulmonary artery or a pulmonary vein, respectively. Bronchial artery interventions can be used successfully in the treatment of hemoptysis, with a low risk of adverse events. Multidetector computed tomography helps provide a vascular road map for the interventional radiologist before bronchial artery embolization.