CRS-related coagulopathy in BCMA targeted CAR-T therapy: a retrospective analysis in a phase I/II clinical trial.

Chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) has shown promising effects in the treatment of patients with refractory/relapsed multiple myeloma (R/R MM) patients. In this retrospective analysis of phase I/II clinical trial (ChiCTR1800017404), 37 patients with R/R MM received their first BCMA-targeted CAR T-cells following lymphodepletion chemotherapy. The response rate was high (97%), while accompanied by a high incidence of adverse events including coagulation dysfunction. Of 37 patients, all (100%) had cytokine release syndrome (CRS) and 34 (91%) developed at least one abnormal coagulation parameter. The values of coagulation parameters were positively correlated with the severity of CRS as well as with the levels of some cytokines, such as interleukin (IL)-6, IL-10, and interferon (IFN)-γ, etc. Furthermore, levels of the plasma tissue factor (TF), Factor X (FX), Factor XII (FXII), and P-selectin also showed a positive correlation with severity of CRS as well as some specific cytokines, which indicates that these factors are likely to play important roles in CRS-related coagulopathy. Our study suggests that there exists relationship in some extent between coagulation disorder and CRS. Moreover, coagulation dysfunction can be managed with daily monitoring and early intervention despite high incidence.

Proportion and associated factors of meeting the 2018 Physical Activity Guidelines for Americans in adults with or at risk for knee osteoarthritis.

OBJECTIVES: Evaluate the prevalence of meeting the updated 2018 Physical Activity Guidelines for Americans (150 unbouted minutes in moderate-to-vigorous intensity physical activity [MVPA]) and determine cross-sectional factors associated with Guideline attainment in a community-based cohort of adults with or at elevated risk for knee osteoarthritis (OA). METHODS: Physical activity was monitored for 1 week in a subset of Osteoarthritis Initiative (OAI) participants with or at increased risk for knee OA. Accelerometer-measured weekly MVPA minutes were calculated; sociodemographic (age, sex, race, education, and working status) and health-related (body mass index [BMI], comorbidity, depressive symptoms, radiographic knee OA, and frequent knee symptoms) factors were assessed. We evaluated the prevalence of meeting 2018 Guidelines and used multivariate partial proportional odds model to identify factors associated with Guideline attainment, controlling for other factors in the model. RESULTS: Among 1922 participants (age 65.1 [standard deviation 9.1] years, BMI 28.4 [4.8] kg/m2, 55.2% women), 44.1% men and 22.2% women met the 2018 PA Guidelines. Adjusted cross-sectional factors associated with not-meeting 2018 Guidelines were: women, older age, higher BMI, non-Whites, depressive symptoms, not working, and frequent knee symptoms. CONCLUSION: In community-recruited adults with or at high risk for knee OA, more than 50% of men and nearly 80% of women failed to achieve the 2018 recommended level of at least 150 weekly unbouted minutes of MVPA. Study findings support gender and racial disparity in Guideline attainment and suggest addressing potentially modifiable factors (e.g., BMI, depressive symptoms, and frequent knee symptoms) to optimize benefits in PA-promoting interventions.

Hip muscle strength and protection against structural worsening and poor function and disability outcomes in knee osteoarthritis.

OBJECTIVE: Examine associations of hip abductor strength with (1) cartilage damage worsening in the tibiofemoral and patellofemoral compartments 2 years later, and (2) poor function and disability outcomes 5 years later. METHODS: Participants had knee osteoarthritis (K/L ≥ 2) in at least one knee. Hip abductor strength was measured using Biodex Dynamometry. Participants underwent 3.0T MRI of both knees at baseline and 2 years later. Baseline-to-2-year cartilage damage progression, defined as any worsening of WORMS cartilage damage score, was assessed at each tibiofemoral and patellofemoral surface. LLFDI (Late-Life Function and Disability Instrument) and Chair-Stand-Rate were recorded at baseline and 5-year follow-up; outcomes analyzed using quintiles. Poor outcomes were defined as remaining in the same low-function quintiles or being in a worse quintile at 5-year follow-up. We analyzed associations of baseline hip abductor strength with cartilage damage worsening and function and disability outcomes using multivariable log-binomial models. RESULTS: 275 knees from 164 persons [age = 63.7 (SD = 9.8) years, 79.3% women] comprised the structural outcome sample, and 187 persons [age = 64.2 (9.7), 78.6% women] the function and disability outcomes sample. Greater baseline hip abductor strength was associated with reduced risks of baseline-to-2-year medial patellofemoral and lateral tibiofemoral cartilage damage worsening [adjusted relative risks (RRs) range: 0.80-0.83) and with reduced risks of baseline-to-5-year poor outcomes for Chair-Stand-Rate and LLFDI Basic Lower-Extremity Function and Disability Limitation (adjusted RRs range: 0.91-0.94). CONCLUSION: Findings support a beneficial role of hip abductor strength for disease modification and for function and disability outcomes, and as a potential therapeutic target in managing knee osteoarthritis.

Reallocating time spent in sleep, sedentary behavior and physical activity and its association with pain: a pilot sleep study from the Osteoarthritis Initiative.

OBJECTIVE: Being physically active has broad health benefits for people with osteoarthritis (OA), including pain relief. Increasing physical activity (PA) requires reducing time in other behaviors within a fixed 24-h day. We examined the potential benefits in relation to pain from trading time in one type of wake or sleep behavior for another. METHOD: In this cross-sectional study, we used isotemporal logistic regression models to examine the estimated effect on pain from replacing time in one behavior with equal time in another, controlling for sociodemographic and health factors. Stratified analysis was conducted by the report of restless sleep. Sleep and wake behaviors [sedentary behavior (SB), light PA, moderate PA] were monitored by accelerometer in a pilot study of 185 Osteoarthritis Initiative (OAI) participants. Outcomes were bodily pain interference and knee pain. RESULTS: Moderate PA substituted for an equivalent time in sleep or other types of wake behaviors was most strongly associated with lower odds of pain (bodily pain interference odds reduced 21-25%, knee pain odds reduced 17-20% per 10-min exchange). These beneficial associations were particularly pronounced in individuals without restless sleep, but not in those with restless sleep, especially for bodily pain interference. CONCLUSION: Interventions promoting moderate physical activities may be most beneficial to address pain among people with or at high risk for knee OA. In addition to encouraging moderate-intensity PA, pain management strategies may also include the identification and treatment of sleep problems.

High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients.

Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD+) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 105/kg and were eventually settled at 1 × 105/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD+ patients achieved MRD-. All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD- with a median follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 105/kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.

Cl2 Elimination in 248 nm Photolysis of (COCl)2 Probed with Cavity Ring-Down Absorption Spectroscopy.

Cavity ring-down absorption spectroscopy (CRDS) is employed to investigate one-photon dissociation of (COCl)2 at 248 nm obtaining a primary Cl2 elimination channel. A ratio of vibrational population is estimated to be 1:(0.12 ± 0.03):(0.011 ± 0.003) for the v = 0, 1, and 2 levels. The quantum yield of Cl2 molecular channel is obtained to be 0.8 ± 0.4 initiated from the X̃ 1Ag ground state surface (COCl)2 via internal conversion. The obtained total quantum yield is attributed to both primary ((COCl)2 + hν → 2CO + Cl2) and secondary reactions (dominated by Cl + COCl → Cl2 + CO). The former is estimated to share a yield of >0.14, while the latter contributes up to 0.66. The photodissociation pathway to the molecular products is calculated to proceed via a four-center transition state (TS) from which Cl2 is eliminated synchronously. Installation of the mirrors with reflectivity of 99.995% in the CRDS apparatus prolongs the ring-down time to 70 µs, thus allowing for the contribution from 17% up to 66% of the total Cl2 yield from secondary reaction depending on the reaction temperature. Despite uncertainty in determining the product yield, the primary Cl2 dissociation channel eliminated from (COCl)2 is observed for the first time.

Association of baseline knee sagittal dynamic joint stiffness during gait and 2-year patellofemoral cartilage damage worsening in knee osteoarthritis.

OBJECTIVE: Knee sagittal dynamic joint stiffness (DJS) describes the biomechanical interaction between change in external knee flexion moment and flexion angular excursion during gait. In theory, greater DJS may particularly stress the patellofemoral (PF) compartment and thereby contribute to PF osteoarthritis (OA) worsening. We hypothesized that greater baseline knee sagittal DJS is associated with PF cartilage damage worsening 2 years later. METHODS: Participants all had OA in at least one knee. Knee kinematics and kinetics during gait were recorded using motion capture systems and force plates. Knee sagittal DJS was computed as the slope of the linear regression line for knee flexion moments vs angles during the loading response phase. Knee magnetic resonance imaging (MRI) scans were obtained at baseline and 2 years later. We assessed the association between baseline DJS and baseline-to-2-year PF cartilage damage worsening using logistic regression with generalized estimating equations (GEE). RESULTS: Our sample had 391 knees (204 persons): mean age 64.2 years (SD 10.0); body mass index (BMI) 28.4 kg/m2 (5.7); 76.5% women. Baseline knee sagittal DJS was associated with baseline-to-2-year cartilage damage worsening in the lateral (OR = 5.35, 95% CI: 2.37-12.05) and any PF (OR = 2.99, 95% CI: 1.27-7.04) compartment. Individual components of baseline DJS (i.e., change in knee moment or angle) were not associated with subsequent PF disease worsening. CONCLUSION: Capturing the concomitant effect of knee kinetics and kinematics during gait, knee sagittal DJS is a potentially modifiable risk factor for PF disease worsening.

Silicon Quantum Dot-Based Fluorescence Turn-On Metal Ion Sensors in Live Cells.

Multiple sensor systems are designed by varying aza-crown ether moiety in silicon quantum dots (SiQDs) for detecting individual Mg(2+), Ca(2+), and Mn(2+) metal ions with significant selectivity and sensitivity. The detection limit of Mg(2+), Ca(2+), and Mn(2+) can reach 1.81, 3.15, and 0.47 µM, respectively. Upon excitation of the SiQDs which are coordinated with aza-crown ethers, the photoinduced electron transfer (PET) takes place from aza-crown ether moiety to the valence band of SiQDs core such that the reduced probability of electron-hole recombination may diminish the subsequent fluorescence. The fluorescence suppression caused by such PET effect will be relieved after selective metal ion is added. The charge-electron binding force between the metal ion and aza-crown ether hinders the PET and thereby restores the fluorescence of SiQDs. The design of sensor system is based on the fluorescence "turn-on" of SiQDs while in search of the appropriate metal ion. For practical application, the sensing capabilities of metal ions in the live cells are performed and the confocal image results reveal their promising applicability as an effective and nontoxic metal ion sensor.

Isoniazid therapy for Mycobacterium tuberculosis infection in HIV clinics, Los Angeles, California.

SETTING: Publicly funded human immunodeficiency virus (HIV) clinics in Los Angeles County, California, USA. BACKGROUND: HIV-infected persons are a high priority group for targeted testing and treatment for Mycobacterium tuberculosis infection in the United States. OBJECTIVE: To describe rates of isoniazid (INH) initiation and completion among HIV-1 and M. tuberculosis co-infected persons in Los Angeles County. DESIGN: We conducted a cross-sectional study using routinely collected surveillance data from publicly funded HIV clinics. We examined differences in INH treatment initiation and completion between four clinic categories: the three largest clinics (Clinics A, B, and C) and 'Other' clinics (pooled data for the remaining 10 clinics). RESULTS: During 2010-2013, 802 (5.3%) of 15 029 HIV-1-infected persons tested positive for M. tuberculosis infection. INH was initiated in 581 (72.4%) persons, of whom 457 (78.7%) completed treatment. We found significant differences between clinics in terms of treatment initiation (range 59.1-93.4%) and completion (range 58.8-82.3%). Overall, 57% (457/802) of HIV and M. tuberculosis co-infected persons completed the recommended treatment (range across clinics 34.8-76.3%). CONCLUSION: We identified significant gaps in the treatment for M. tuberculosis infection among HIV-infected persons in Los Angeles County. Interventions are needed to improve initiation and completion of treatment for M. tuberculosis infection in this population.

Synthesis of urea in cometary model ices and implications for Comet 67P/Churyumov-Gerasimenko.

Urea is considered a fundamental building block in prebiotic chemistry. Its formation on early Earth has not yet been explained satisfactorily and exogenous delivery has been considered. We report on the synthesis along with the first online and in situ identification of urea after exposing inorganic ices to ionizing radiation.

On the formation of pyridine in the interstellar medium.

Nitrogen-substituted polycyclic aromatic hydrocarbons (NPAHs) have been proposed to play a key role in the astrochemical evolution of the interstellar medium, but the formation mechanism of even their simplest building block - the aromatic pyridine molecule - has remained elusive for decades. Here we reveal a potential pathway to a facile pyridine (C5H5N) synthesis via the reaction of the cyano vinyl (C2H2CN) radical with vinyl cyanide (C2H3CN) in high temperature environments simulating conditions in carbon-rich circumstellar envelopes of Asymptotic Giant Branch (AGB) stars like IRC+10216. Since this reaction is barrier-less, pyridine can also be synthesized via this bimolecular reaction in cold molecular clouds such as in TMC-1. The synchronized aromatization of precursors readily available in the interstellar medium leading to nitrogen incorporation into the aromatic rings would open up a novel route to pyridine derivatives such as vitamin B3 and pyrimidine bases as detected in carbonaceous chondrites like Murchison.

Characterization of molecular channel in photodissociation of SOCl2 at 248 nm: Cl2 probing by cavity ring-down absorption spectroscopy.

A primary elimination channel of the chlorine molecule in the one-photon dissociation of SOCl2 at 248 nm was investigated using cavity ring-down absorption spectroscopy (CRDS). By means of spectral simulation, the ratio of the vibrational population in the v = 0, 1, and 2 levels was evaluated to be 1 : (0.10 ± 0.02) : (0.009 ± 0.005), corresponding to a Boltzmann vibrational temperature of 340 ± 30 K. The Cl2 molecular channel was obtained with a quantum yield of 0.4 ± 0.2 from the X(1)A' ground state of SOCl2via internal conversion. The dissociation mechanism differs from a prior study where a smaller yield of <3% was obtained, initiated from the 2(1)A' excited state. Temperature-dependence measurements of the Cl2 fragment turn out to support our mechanism. With the aid of ab initio potential energy calculations, two dissociation routes to the molecular products were found, including one synchronous dissociation pathway via a three-center transition state (TS) and the other sequential dissociation pathway via a roaming-mediated isomerization TS. The latter mechanism with a lower energy barrier dominates the dissociation reaction.

External knee adduction and flexion moments during gait and medial tibiofemoral disease progression in knee osteoarthritis.

OBJECTIVE: Test the hypothesis that greater baseline peak external knee adduction moment (KAM), KAM impulse, and peak external knee flexion moment (KFM) during the stance phase of gait are associated with baseline-to-2-year medial tibiofemoral cartilage damage and bone marrow lesion progression, and cartilage thickness loss. METHODS: Participants all had knee OA in at least one knee. Baseline peak KAM, KAM impulse, and peak KFM (normalized to body weight and height) were captured and computed using a motion analysis system and six force plates. Participants underwent MRI of both knees at baseline and 2 years later. To assess the association between baseline moments and baseline-to-2-year semiquantitative cartilage damage and bone marrow lesion progression and quantitative cartilage thickness loss, we used logistic and linear regressions with generalized estimating equations (GEE), adjusting for gait speed, age, gender, disease severity, knee pain severity, and medication use. RESULTS: The sample consisted of 391 knees (204 persons): mean age 64.2 years (SD 10.0); BMI 28.4 kg/m(2) (5.7); 156 (76.5%) women. Greater baseline peak KAM and KAM impulse were each associated with worsening of medial bone marrow lesions, but not cartilage damage. Higher baseline KAM impulse was associated with 2-year medial cartilage thickness loss assessed both as % loss and as a threshold of loss, whereas peak KAM was related only to % loss. There was no relationship between baseline peak KFM and any medial disease progression outcome measures. CONCLUSION: Findings support targeting KAM parameters in an effort to delay medial OA disease progression.

Combined crossed molecular beam and ab initio investigation of the reaction of boron monoxide (BO; X(2)Σ(+)) with 1,3-butadiene (CH2CHCHCH2; X(1)Ag) and its deuterated counterparts.

The reactions of the boron monoxide ((11)BO; X(2)Σ(+)) radical with 1,3-butadiene (CH2CHCHCH2; X(1)Ag) and its partially deuterated counterparts, 1,3-butadiene-d2 (CH2CDCDCH2; X(1)Ag) and 1,3-butadiene-d4 (CD2CHCHCD2; X(1)Ag), were investigated under single collision conditions exploiting a crossed molecular beams machine. The experimental data were combined with the state-of-the-art ab initio electronic structure calculations and statistical RRKM calculations to investigate the underlying chemical reaction dynamics and reaction mechanisms computationally. Our investigations revealed that the reaction followed indirect scattering dynamics through the formation of (11)BOC4H6 doublet radical intermediates via the barrierless addition of the (11)BO radical to the terminal carbon atom (C1/C4) and/or the central carbon atom (C2/C3) of 1,3-butadiene. The resulting long-lived (11)BOC4H6 intermediate(s) underwent isomerization and/or unimolecular decomposition involving eventually at least two distinct atomic hydrogen loss pathways to 1,3-butadienyl-1-oxoboranes (CH2CHCHCH(11)BO) and 1,3-butadienyl-2-oxoboranes (CH2C ((11)BO)CHCH2) in overall exoergic reactions via tight exit transition states. Utilizing partially deuterated 1,3-butadiene-d2 and -d4, we revealed that the hydrogen loss from the methylene moiety (CH2) dominated with 70 ± 10% compared to an atomic hydrogen loss from the methylidyne group (CH) of only 30 ± 10%; these data agree nicely with the theoretically predicted branching ratio of 80% versus 19%.

Combined crossed molecular beam and ab initio investigation of the multichannel reaction of boron monoxide (BO; X2Σ+) with Propylene (CH3CHCH2; X1A'): competing atomic hydrogen and methyl loss pathways.

The reaction dynamics of boron monoxide ((11)BO; X(2)Σ(+)) with propylene (CH(3)CHCH(2); X(1)A') were investigated under single collision conditions at a collision energy of 22.5 ± 1.3 kJ mol(-1). The crossed molecular beam investigation combined with ab initio electronic structure and statistical (RRKM) calculations reveals that the reaction follows indirect scattering dynamics and proceeds via the barrierless addition of boron monoxide radical with its radical center located at the boron atom. This addition takes place to either the terminal carbon atom (C1) and/or the central carbon atom (C2) of propylene reactant forming (11)BOC(3)H(6) intermediate(s). The long-lived (11)BOC(3)H(6) doublet intermediate(s) underwent unimolecular decomposition involving at least three competing reaction mechanisms via an atomic hydrogen loss from the vinyl group, an atomic hydrogen loss from the methyl group, and a methyl group elimination to form cis-/trans-1-propenyl-oxo-borane (CH(3)CHCH(11)BO), 3-propenyl-oxo-borane (CH(2)CHCH(2)(11)BO), and ethenyl-oxo-borane (CH(2)CH(11)BO), respectively. Utilizing partially deuterated propylene (CD(3)CHCH(2) and CH(3)CDCD(2)), we reveal that the loss of a vinyl hydrogen atom is the dominant hydrogen elimination pathway (85 ± 10%) forming cis-/trans-1-propenyl-oxo-borane, compared to the loss of a methyl hydrogen atom (15 ± 10%) leading to 3-propenyl-oxo-borane. The branching ratios for an atomic hydrogen loss from the vinyl group, an atomic hydrogen loss from the methyl group, and a methyl group loss are experimentally derived to be 26 ± 8%:5 ± 3%:69 ± 15%, respectively; these data correlate nicely with the branching ratios calculated via RRKM theory of 19%:5%:75%, respectively.

Theoretical study on reaction mechanism of ground-state cyano radical with 1,3-butadiene: prospect of pyridine formation.

The reaction of ground-state cyano radicals, CN(X(2)Σ(+)), with the simplest polyene, 1,3-butadiene (C4H6(X(1)Ag)), is investigated to explore probable routes and feasibility to form pyridine at ultralow temperatures. The isomerization and dissociation channels for each of the seven initial collision complexes are characterized by utilizing the unrestricted B3LYP/cc-pVTZ and the CCSD(T)/cc-pVTZ calculations. With facilitation of RRKM rate constants, through ab initio paths composed of 7 collision complexes, 331 intermediates, 62 hydrogen atom, 71 hydrogen molecule, and 3 hydrogen cyanide dissociated products, the most probable paths at collision energies up to 10 kcal/mol, and thus the reaction mechanism, are determined. Subsequently, the corresponding rate equations are solved that the concentration evolutions of collision complexes, intermediates, and products versus time are obtained. As a result, the final products and yields are determined. The low-energy routes for the formation of most thermodynamically stable product, pyridine, are identified. This study, however, predicts that seven collision complexes would produce predominately 1-cyano-1,3-butadiene, CH2CHCHCHCN (p2) plus atomic hydrogen via the collision complex c1(CH2CHCHCH2CN) and intermediate i2(CH2CHCH2CHCN), with a very minor amount of pyridine. Our scheme also effectively excludes the presence of 2-cyano-1,3-butadiene, which has energy near-degenerate to 1-cyano-1,3-butadiene, as supported by experimental findings.

Comparison of tumor neovasculature-targeted paramagnetic nanoliposomes for MRI in mice xenograft models.

INTRODUCTION: Neovasculature imaging is a promising approach for tumor diagnosis. We constructed tumor neovasculature targeted paramagnetic nanoliposomes with RGD10, F56, and K237 peptides, which can bind to Integrin αvß3 and VEGFR-1, VEGFR-2, respectively, and compared their potential value as MRI contrast agents for detecting small tumors in animal models. MATERIALS AND METHODS: Peptide-Ahx-palmitic acid conjugate was synthesized using Fmoc solid-phase synthesis chemistry. Targeted paramagnetic nanoliposomes were prepared by the thin film dispersion-sonication method. The tumor signal enhancements of liposome particles were evaluated by MRI in a xenograft mice model. RESULTS: The apparent affinity constants of RGD10, K237, and F56 peptides binding to their cell receptors were 9.15 × 10(7), 6.01 × 10(7), and 3.85 × 10(7) mol/L, respectively. RGD10 and K237 targeted paramagnetic nanoliposomes have shown much greater tumor-specific MRI signal enhancement in xenograft of the nude mice compared to F56 targeted paramagnetic nanoliposome. Tumor signal enhancement rate (SER %) increased 2.21 ± 0.09 and 1.82 ± 0.05 fold, respectively, for RGD10 and K237 compared to non-targeted control in T1 weighted MR image. CONCLUSION: RGD10 and K237 targeted paramagnetic nanoliposomes can be developed as potential tumor-specific MRI contrast agents and are helpful for tumor detection.

Varus thrust and knee frontal plane dynamic motion in persons with knee osteoarthritis.

OBJECTIVE: Varus thrust visualized during walking is associated with a greater medial knee load and an increased risk of medial knee osteoarthritis (OA) progression. Little is known about how varus thrust presence determined by visual observation relates to quantitative gait kinematic data. We hypothesized that varus thrust presence is associated with greater knee frontal plane dynamic movement during the stance phase of gait. METHODS: Participants had knee OA in at least one knee. Trained examiners assessed participants for varus thrust presence during ambulation. Frontal plane knee motion during ambulation was captured using external passive reflective markers and an 8-camera motion analysis system. To examine the cross-sectional relationship between varus thrust and frontal plane knee motion, we used multivariable regression models with the quantitative motion measures as dependent variables and varus thrust (present/absent) as predictor; models were adjusted for age, gender, body mass index (BMI), gait speed, and knee static alignment. RESULTS: 236 persons [mean BMI: 28.5 kg/m(2) (standard deviation (SD) 5.5), mean age: 64.9 years (SD 10.4), 75.8% women] contributing 440 knees comprised the study sample. 82 knees (18.6%) had definite varus thrust. Knees with varus thrust had greater peak varus angle and greater peak varus angular velocity during stance than knees without varus thrust (mean differences 0.90° and 6.65°/s, respectively). These patterns remained significant after adjusting for age, gender, BMI, gait speed, and knee static alignment. CONCLUSION: Visualized varus thrust during walking was associated with a greater peak knee varus angular velocity and a greater peak knee varus angle during stance phase of gait.

The immune response to tuberculosis infection in the setting of Helicobacter pylori and helminth infections.

We screened 176 healthy, adult (aged 18-55 years) US refugees from tuberculosis (TB)-endemic countries to evaluate whether cytokine responses to latent TB infection (LTBI) are modified in the setting of concurrent H. pylori and helminth infection. As measured by the Quantiferon-TB GOLD interferon-γ release assay, a total 38 (22%) subjects had LTBI, of which 28 (74%) also were H. pylori seropositive and/or helminth infected. Relative to ten subjects with LTBI only, 16 subjects with concurrent H. pylori infection had significantly elevated levels of IFN-γ, and nine subjects with both H. pylori and helminth infection had significantly elevated levels of IFN-γ, IL-2, IL-13, and IL-5. H. pylori is associated with enhanced IFN-γ responses to TB, even in the setting of concurrent helminth infection. Efficacy of TB vaccines may vary with the co-existence of these three infections in the developing world.

Molecular elimination of Br2 in photodissociation of CH2BrC(O)Br at 248 nm using cavity ring-down absorption spectroscopy.

The primary elimination channel of bromine molecule in one-photon dissociation of CH(2)BrC(O)Br at 248 nm is investigated using cavity ring-down absorption spectroscopy. By means of spectral simulation, the ratio of nascent vibrational population in v = 0, 1, and 2 levels is evaluated to be 1:(0.5 ± 0.1):(0.2 ± 0.1), corresponding to a Boltzmann vibrational temperature of 581 ± 45 K. The quantum yield of the ground state Br(2) elimination reaction is determined to be 0.24 ± 0.08. With the aid of ab initio potential energy calculations, the obtained Br(2) fragments are anticipated to dissociate on the electronic ground state, yielding vibrationally hot Br(2) products. The temperature-dependence measurements support the proposed pathway via internal conversion. For comparison, the Br(2) yields are obtained analogously from CH(3)CHBrC(O)Br and (CH(3))(2)CBrC(O)Br to be 0.03 and 0.06, respectively. The trend of Br(2) yields among the three compounds is consistent with the branching ratio evaluation by Rice-Ramsperger-Kassel-Marcus method. However, the latter result for each molecule is smaller by an order of magnitude than the yield findings. A non-statistical pathway so-called roaming process might be an alternative to the Br(2) production, and its contribution might account for the underestimate of the branching ratio calculations.