Engineered E. coli for D-pantothenic acid production with an acetolactate isomeroreductase mutant.

D-Pantothenic acid, as a momentous vitamin, is extensively applied to feed, medicine, cosmetics and other fields. However, there are still limitations to produce D-pantothenic acid by microbial fermentation at present. In this paper, we constructed a recombinant strain for D-pantothenic acid production by blocking the organic acid pathway, boosting pyruvate biosynthesis, relieving feedback inhibition of acetolactate synthase, improving glucose intake capacity, and modifying essential genes in the metabolic pathway. In addition, a new acetolactate isomeroreductase mutant V412A origin from Escherichia coli (EcAHAIR) encoded by ilvC was obtained to explore its substrate promiscuity. Compared with the wild type, the variant EcAHAIR-V412A has reduced steric hindrance and enhanced intermolecular forces, resulting in a high affinity for 2-acetolactate. Eventually, the fermentation production of the final strain DPAN19/trc-ilvCV412A reached 4.65 g/L, increased by 192.5% compared with strain DPA8 in shake flask cultivation and produced 62.82 g/L D-pantothenic acid in a 5 L bioreactor. The metabolic engineering strategies and enzyme modification approaches described in this paper provide a particular perspective for the bio-manufacturing of D-pantothenic acid, branched-chain amino acids and its derivates.

Reactive aldehyde chemistry explains the missing source of hydroxyl radicals.

Hydroxyl radicals (OH) determine the tropospheric self-cleansing capacity, thus regulating air quality and climate. However, the state-of-the-art mechanisms still underestimate OH at low nitrogen oxide and high volatile organic compound regimes even considering the latest isoprene chemistry. Here we propose that the reactive aldehyde chemistry, especially the autoxidation of carbonyl organic peroxy radicals (R(CO)O2) derived from higher aldehydes, is a noteworthy OH regeneration mechanism that overwhelms the contribution of the isoprene autoxidation, the latter has been proved to largely contribute to the missing OH source under high isoprene condition. As diagnosed by the quantum chemical calculations, the R(CO)O2 radicals undergo fast H-migration to produce unsaturated hydroperoxyl-carbonyls that generate OH through rapid photolysis. This chemistry could explain almost all unknown OH sources in areas rich in both natural and anthropogenic emissions in the warm seasons, and may increasingly impact the global self-cleansing capacity in a future low nitrogen oxide society under carbon neutrality scenarios.

Rapid Atmospheric Reactions between Criegee Intermediates and Hypochlorous Acid.

Hypochlorous acid (HOCl) is a paramount compound in the atmosphere due to its significant contribution to both tropospheric oxidation capacity and ozone depletion. The main removal routes for HOCl are photolysis and the reaction with OH during the daytime, while these processes are unimportant during the nighttime. Here, we report the rapid reactions of Criegee intermediates (CH2OO and anti/syn-CH3CHOO) with HOCl by using high-level quantum chemical methods as the benchmark; their accuracy is close to coupled cluster theory with single, double, and triple excitations and quasiperturbative connected quadruple excitations with a complete basis limit by extrapolation [CCSDT(Q)/CBS]. Their rate constants have been calculated by using a dual-level strategy; this combines conventional transition state theory calculated at the benchmark level with variational transition state theory with small-curvature tunneling by a validated density functional method. We find that the introduction of the methyl group into Criegee intermediates not only affects their reactivities but also exerts a remarkable influence on anharmonicity. The calculated results uncover that anharmonicity increases the rate constants of CH2OO + HOCl by a factor of 18-5, while it is of minor importance in the anti/syn-CH3CHOO + HOCl reaction at 190-350 K. The present findings reveal that the loose transition state for anti-CH3CHOO and HOCl is a rate-determining step at 190-350 K. We also find that the reaction of Criegee intermediates with HOCl contributes significantly to the sink of HOCl during the nighttime in the atmosphere.

Advances in the research on myokine-driven regulation of bone metabolism.

The traditional view posits that bones and muscles interact primarily through mechanical coupling. However, recent studies have revealed that myokines, proteins secreted by skeletal muscle cells, play a crucial role in the regulation of bone metabolism. Myokines are widely involved in bone metabolism, influencing bone resorption and formation by interacting with factors related to bone cell secretion or influencing bone metabolic pathways. Here, we review the research progress on the myokine regulation of bone metabolism, discuss the mechanism of myokine regulation of bone metabolism, explore the pathophysiological relationship between sarcopenia and osteoporosis, and provide future perspectives on myokine research, with the aim of identify potential specific diagnostic markers and therapeutic entry points.

[Influence of thyroid function on the fetal fraction during second trimester of pregnancy].

OBJECTIVE: To assess the influence of thyroid function on the fetal fraction (FF) during the second trimester of pregnancy. METHODS: A total of 1 861 pregnant women undergoing non-invasive prenatal testing (NIPT) and thyroxine function testing at 12 ~ 26 gestational weeks at the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital from January 2016 to December 2020 were selected as the study subjects. Univariate analysis and multivariate regression models were used to assess the correlation between free thyroxine 4 (FT4) levels and FF. RESULTS: Univariate linear regression analysis indicated that the FF is correlated to the level of FT4 (b = 0.035, P < 0.001). The median fetal FF was 10.78% (IQR: 8.2%, 13.82%), and this has increased along with the level of FT4 from 10.58% at <= 12.0 pmol/L to 11.77% at > 16.0 pmol/L. After further adjustment of gestational age and body mass index (BMI), the FF showed an increase trend along with the increase of FT4 levels, and a trend test also showed a statistical significance (Ptrend < 0.001). CONCLUSION: Maternal FF can be affected by the level of free thyroxine during the second trimester of pregnancy.

Kinetics of Sulfur Trioxide Reaction with Water Vapor to Form Atmospheric Sulfuric Acid.

Although experimental methods can be used to obtain the quantitative kinetics of atmospheric reactions, experimental data are often limited to a narrow temperature range. The reaction of SO3 with water vapor is important for elucidating the formation of sulfuric acid in the atmosphere; however, the kinetics is uncertain at low temperatures. Here, we calculate rate constants for reactions of sulfur trioxide with two water molecules. We consider two mechanisms: the SO3···H2O + H2O reaction and the SO3 + (H2O)2 reaction. We find that beyond-CCSD(T) contributions to the barrier heights are very large, and multidimensional tunneling, unusually large anharmonicity of high-frequency modes, and torsional anharmonicity are important for obtaining quantitative kinetics. We find that at lower temperatures, the formation of the termolecular precursor complexes, which is often neglected, is rate-limiting compared to passage through the tight transition states. Our calculations show that the SO3···H2O + H2O mechanism is more important than the SO3 + (H2O)2 mechanism at 5-50 km altitudes. We find that the rate ratio between SO3···H2O + H2O and SO3 + (H2O)2 is greater than 20 at altitudes between 10 and 35 km, where the concentration of SO3 is very high.

Structural insights into the transcription activation mechanism of the global regulator GlnR from actinobacteria.

In actinobacteria, an OmpR/PhoB subfamily protein called GlnR acts as an orphan response regulator and globally coordinates the expression of genes responsible for nitrogen, carbon, and phosphate metabolism in actinobacteria. Although many researchers have attempted to elucidate the mechanisms of GlnR-dependent transcription activation, progress is impeded by lacking of an overall structure of GlnR-dependent transcription activation complex (GlnR-TAC). Here, we report a co-crystal structure of the C-terminal DNA-binding domain of GlnR (GlnR_DBD) in complex with its regulatory cis-element DNA and a cryo-EM structure of GlnR-TAC which comprises Mycobacterium tuberculosis RNA polymerase, GlnR, and a promoter containing four well-characterized conserved GlnR binding sites. These structures illustrate how four GlnR protomers coordinate to engage promoter DNA in a head-to-tail manner, with four N-terminal receiver domains of GlnR (GlnR-RECs) bridging GlnR_DBDs and the RNAP core enzyme. Structural analysis also unravels that GlnR-TAC is stabilized by complex protein-protein interactions between GlnR and the conserved ß flap, σAR4, αCTD, and αNTD domains of RNAP, which are further confirmed by our biochemical assays. Taken together, these results reveal a global transcription activation mechanism for the master regulator GlnR and other OmpR/PhoB subfamily proteins and present a unique mode of bacterial transcription regulation.

Correlative Escherichia coli Transcription Rate and Bubble Conformation Remodeled by NusA and NusG.

Transcription is highly regulated by a variety of transcription factors, among which NusA and NusG act contradictorily in Escherichia coli (E. coli) that NusA stabilizes a paused RNA polymerase (RNAP) and NusG suppresses it. The mechanism of the NusA and NusG regulations on RNAP transcription has been addressed, but their effect on the conformational changes of the transcription bubble correlated with transcription kinetics remains elusive. By using single-molecule magnetic trap, we identify a reduction in the transcription rate of ∼40% events by NusA. Although the rest ∼60% of transcription events exhibit unaffected transcription rates, a NusA-enhanced standard deviation of the transcription rate is observed. NusA remodeling also increases the extent of DNA unwinding in the transcription bubble by 1-2 base pairs, which can be reduced by NusG. The NusG remodeling is more significant on the RNAP molecules with reduced transcription rates rather than those without. Our results provide a quantitative view on the mechanisms of transcriptional regulation by NusA and NusG factors.

Quantitative kinetics for the atmospheric reactions of Criegee intermediates with acetonitrile.

Obtaining quantitative kinetics of Criegee intermediates is of paramount significance in the atmosphere. However, there are limited reports on the kinetics of Criegee intermediates. Here, by using our very recently developed dual-level strategy, we report the quantitative kinetics of the reaction of Criegee intermediates (CH2OO/anti-CH3CHOO/syn-CH3CHOO) with acetonitrile (CH3CN). The dual-level strategy combines post-CCSD(T) calculations for transition state theory with the validated M06CR/MG3S and M11-L/MG3S functional methods for direct dynamics calculations using canonical variational transition state theory with small-curvature tunneling to obtain recrossing effects and tunneling coefficients. We show that W3X-L//DF-CCSD(T)-F12b/jun-cc-pVDZ can be used to obtain quantitative enthalpies of activation at 0 K in the reactions of Criegee intermediates with CH3CN. We find that the CH2OO/anti-CH3CHOO/syn-CH3CHOO + CH3CN reactions only depend on temperature. Moreover, we also find that their rate constants are dominantly determined by the enthalpy of activation at 0 K and recrossing effects and tunneling are negligible. The present findings also show that the CH2OO/anti-CH3CHOO + CH3CN reactions have negative temperature dependence in the range of 190-350 K. In the atmosphere, we reveal that the reactions of CH2OO and anti-CH3CHOO with CH3CN are significant acetonitrile sinks, leading to the formation of N-formylacetamide and diacetamide. The present findings will be useful for obtaining quantitative kinetics of Criegee intermediates and understanding acetonitrile sinks.

Structural basis of three different transcription activation strategies adopted by a single regulator SoxS.

Transcription activation is established through extensive protein-protein and protein-DNA interactions that allow an activator to engage and remodel RNA polymerase. SoxS, a global transcription activator, diversely regulates subsets of stress response genes with different promoters, but the detailed SoxS-dependent transcription initiation mechanisms remain obscure. Here, we report cryo-EM structures of three SoxS-dependent transcription activation complexes (SoxS-TACI, SoxS-TACII and SoxS-TACIII) comprising of Escherichia coli RNA polymerase (RNAP), SoxS protein and three representative classes of SoxS-regulated promoters. The structures reveal that SoxS monomer orchestrates transcription initiation through specific interactions with the promoter DNA and different conserved domains of RNAP. In particular, SoxS is positioned in the opposite orientation in SoxS-TACIII to that in SoxS-TACI and SoxS-TACII, unveiling a novel mode of transcription activation. Strikingly, two universally conserved C-terminal domains of alpha subunit (αCTD) of RNAP associate with each other, bridging SoxS and region 4 of σ70. We show that SoxS interacts with RNAP directly and independently from DNA, remodeling the enzyme to activate transcription from cognate SoxS promoters while repressing transcription from UP-element containing promoters. Our data provide a comprehensive summary of SoxS-dependent promoter architectures and offer new insights into the αCTD contribution to transcription control in bacteria.

The Effect of Elevated Alanine Transaminase on Non-invasive Prenatal Screening Failures.

Objective: To determine the effects of alanine transaminase (ALT) levels on the screening failure rates or "no calls" due to low fetal fraction (FF) to obtain a result in non-invasive prenatal screening (NIPS). Methods: NIPS by sequencing and liver enzyme measurements were performed in 7,910 pregnancies at 12-26 weeks of gestation. Univariate and multivariable regression models were used to evaluate the significant predictors of screening failure rates among maternal characteristics and relevant laboratory parameters. Results: Of the 7,910 pregnancies that met the inclusion criteria, 134 (1.69%) had "no calls." Multiple logistic regression analysis demonstrated that increased body mass index, ALT, prealbumin, albumin levels, and in vitro fertilization (IVF) conception rates were independently associated with screening failures. The test failure rate was higher (4.34 vs. 1.41%; P < 0.001) in IVF pregnancies relative to those with spontaneous conceptions. Meanwhile, the screening failure rates increased with increasing ALT levels from 1.05% at ≤10 U/L to 3.73% at >40 U/L. In particular, IVF pregnancies with an ALT level of >40 U/L had a higher test failure rate (9.52%). Compared with that for an ALT level of ≤10 U/L, the adjusted odds ratio of "no calls" for ALT levels of 10-20, 21-40, and >40 U/L was 1.204 [95% confidence interval (CI), 0.709-2.045], 1.529 (95% CI, 0.865-2.702), and 2.764 (95% CI, 1.500-5.093) (P trend < 0.001), respectively. Conclusions: Increased ALT and IVF conceptions were associated with a higher screening failure rates in NIPS. Therefore, a feasible strategy to adjust these factors to reduce the probability of "no calls" due to low FF would be of great clinical significance.

Studies on the electrostatic effects of stretched PVDF films and nanofibers.

The electroactive ß-phase in Poly (vinylidene fluoride, PVDF) is the most desirable conformation due to its highest pyro- and piezoelectric properties, which make it feasible to be used as flexible sensors, wearable electronics, and energy harvesters etc. In this study, we successfully developed a method to obtain high-content ß-phase PVDF films and nanofiber meshes by mechanical stretching and electric spinning. The phase transition process and pyro- and piezoelectric effects of stretched films and nanofiber meshes were characterized by monitoring the polarized light microscopy (PLM) images, outputting currents and open-circuit voltages respectively, which were proved to be closely related to stretching ratio (λ) and concentrations. This study could expand a new route for the easy fabrication and wide application of PVDF films or fibers in wearable electronics, sensors, and energy harvesting devices.

Risk assessment and identification of HIV infection among men who have sex with men: a cross-sectional study in Southwest China.

OBJECTIVES: The HIV epidemic is around 7%-20% among men who have sex with men (MSM) in Southwest China. The low HIV-testing rate highlights the need for tools to identify high-risk MSM in resource-limited regions. Our aim was, therefore, to evaluate the HIV RISK Assessment Tool for HIV prediction and to characterise the primary infection among MSM in Southwest China. DESIGN: A cross-sectional survey was conducted in Guizhou province between January and December 2018. Participants were recruited from gay communities, among whom the HIV RISK Assessment Tool was evaluated. Logistic regression was used to analyse items associated with HIV and the area under the curve (AUC) of the receiver operating curve was calculated to quantify discrimination performance. PARTICIPANTS: 1330 MSM participants, of which 83 (6.2%) tested as HIV positive. RESULTS: A higher composite score of the tool (adjusted OR (aOR) 9.33, 95% CI 4.57 to 19.05) was independently associated with HIV infection. Items positively associated with HIV infection included having 2-5 same sex partners (aOR 2.43, 95% CI 1.28 to 4.64), always (aOR 5.93, 95% CI 1.59 to 22.13) or sometimes (aOR 4.25, 95% CI 2.09 to 8.64) having unprotected anal intercourse, taking both insertive and receptive sex roles (aOR 4.95, 95% CI 2.57 to 9.53) or only the receptive sex role (aOR 2.26, 95% CI 1.21 to 4.24). The tool showed an optimal discrimination ability (AUC=0.827), with a specificity of 0.747 and sensitivity of 0.785. Five MSM were identified with primary infection and had similar sexual risk behaviors as HIV-positive participants. CONCLUSIONS: The HIV RISK Assessment Tool showed an overall good performance in predicting HIV risk among MSM in Guizhou province where the prevalence is still severe. This tool also demonstrated a potential to identify primary infection and is worth being promoted in resource-limited regions.

Microdeletion and microduplication of 1p36.11p35.3 involving AHDC1 contribute to neurodevelopmental disorder.

Xia-Gibbs syndrome is a rare genetic condition characterized by intellectual disability, growth retardation, delayed psychomotor development with absent or poor expressive language, distinctive facial features, hypotonia, laryngomalacia and obstructive sleep apnea. At present, Xia-Gibbs syndrome has been reported to be mainly caused by truncating mutations in AHDC1 gene located on chromosome 1p36.11. However, the evidence supporting AHDC1 deletion as a cause of this syndrome is still limited. Here we report an 8-year-old boy carrying a de novo 575 Kb microdeletion at 1p36.11 including AHDC1 gene. The boy is characterized by intellectual disability, developmental delay, short stature, expressive language delay, facial dysmorphism, obstructive sleep apnea and multiple congenital anomalies, which are mostly consistent with the characteristics of Xia-Gibbs syndrome. Therefore, we provide further supporting evidence that AHDC1 deletion causes Xia-Gibbs syndrome through a haploinsufficiency mechanism. Currently, clinical consequences of AHDC1 gene duplication has never been reported. Here, we identify a de novo 480 Kb duplication at 1p36.11p35.3 spanning the entire AHDC1 gene in a 2-year-8-month boy, who displays similar clinical features with that of Xia-Gibbs syndrome, in particular, expressive language delay, hypotonia, laryngomalacia and obstructive sleep apnea, as well as mirrored phenotypes such as overgrowth and advanced bone age. WES test excludes to the degree possible other known genetic causes. This case suggests that AHDC1 gene duplication may be clinical significance.

Rice OsDOF15 contributes to ethylene-inhibited primary root elongation under salt stress.

In early seedlings, the primary root adapts rapidly to environmental changes through the modulation of endogenous hormone levels. The phytohormone ethylene inhibits primary root elongation, but the underlying molecular mechanism of how ethylene-reduced root growth is modulated in environmental changes remains poorly understood. Here, we show that a novel rice (Oryza sativa) DOF transcription factor OsDOF15 positively regulates primary root elongation by regulating cell proliferation in the root meristem, via restricting ethylene biosynthesis. Loss-of-function of OsDOF15 impaired primary root elongation and cell proliferation in the root meristem, whereas OsDOF15 overexpression enhanced these processes, indicating that OsDOF15 is a key regulator of primary root elongation. This regulation involves the direct interaction of OsDOF15 with the promoter of OsACS1, resulting in the repression of ethylene biosynthesis. The control of ethylene biosynthesis by OsDOF15 in turn regulates cell proliferation in the root meristem. OsDOF15 transcription is repressed by salt stress, and OsDOF15-mediated ethylene biosynthesis plays a role in inhibition of primary root elongation by salt stress. Thus, our data reveal how the ethylene-inhibited primary root elongation is finely controlled by OsDOF15 in response to environmental signal, a novel mechanism of plants responding to salt stress and transmitting the information to ethylene biosynthesis to restrict root elongation.

MAPK/c-Jun signaling pathway contributes to the upregulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL induced by Epstein-Barr virus-encoded BARF1 in gastric carcinoma cells.

BARF1, encoded by Epstein-Barr virus (EBV), has been hypothesized to function as an oncogene, which was expressed in gastric carcinoma cells. Additionally, it has been reported that the anti-apoptotic function is closely associated with the expression of the B-cell lymphoma-2 (Bcl-2) protein. In addition, the signaling pathway has been reported to be involved in numerous diseases, including the mitogen-activated protein kinase (MAPK) cascade. In order to study the specific mechanism of anti-apoptotic function, BARF1-stably-expressing immortalized normal human embryo gastric epithelial cell line GES1 (GES-BARF1), and well-, moderately- and poorly-differentiated gastric carcinoma cell lines, MKN28 (which has been reported to be contaminated with the moderately-differentiated MKN74 gastric carcinoma cell line), SGC7901 and BGC823 (MKN-BARF1, SGC-BARF1 and BGC-BARF1, respectively) (GCC-BARF1) were constructed, with transfection of cells with the empty vector pSG5 acting as controls. Western blot analysis was performed to analyze the protein expression and the phosphorylation levels. Compared with the controls, it was found that the protein expression levels of c-Jun, Bcl-2 and B-cell lymphoma-extra large (Bcl-xL), as well as the phosphorylation levels of c-Jun, c-Jun N-terminal kinase (JNK) 1/2/3, p38 and extracellular signal-regulated kinase (ERK) 1/2 proteins were upregulated in 3 GCC-BARF1 but not significantly changed in GES-BARF1. The expression levels of the c-Jun, Bcl-2 and Bcl-xL proteins, and levels of c-Jun protein phosphorylation were significantly decreased in SGC-BARF1 cells subsequent to treatment with SP600125, SB203580, and U0126, which were the specific inhibitors of JNK1/2/3, p38 and ERK1/2 respectively. In addition, there was a gradual increase in the protein expression and phosphorylation levels between normal gastric epithelial cells, and well-differentiated, moderately-differentiated and poorly-differentiated gastric carcinoma cells, but this was not statistically significant. Therefore, the present study hypothesized that JNK1/2/3-, p38- and ERK1/2-MAPK/c-Jun cascade signaling pathways may contribute to the upregulation of the expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL induced by BARF1 in gastric carcinoma cells. This mechanism may mainly work in the progressive phase of the development in EBV-associated gastric carcinoma.

Differences of Matrix Metalloproteinase 2 Expression between Left and Right Ventricles in Response to Nandrolone Decanoate and/or Swimming Training in Mice.

BACKGROUND: Matrix metalloproteinase (MMP)-2 plays an important role in the remodeling of left ventricles (LVs) and right ventricles (RVs). We investigated the differences of MMP-2 expression between LV and RV in response to nandrolone decanoate (ND), swimming training (ST), and combined ND and ST (NS) in mice, based on their structural, functional, and biochemical characteristics. METHODS: Totally 28 male C57B1 mice (6 weeks old; 20-23 g) were divided into four groups, including the control (n = 7), ND (n = 6), ST (n = 8), and NS (n = 7) groups. After respective treatments for 8 weeks, echocardiographic examination was used to assess the cardiac structure and function. Van Gieson stain was used to examine the fibrosis of LV and RV in response to different treatments, and Western blotting analysis was performed to explore different MMP-2 expressions between LV and RV in response to ND and/or ST. Analysis of variance was used for comparing the four groups. RESULTS: At 8 weeks, right ventricular dimension/body weight in the ND group was larger than the other three groups (F = 7.12, P < 0.05) according to the echocardiographic examination. Fibrosis induced by ND administration was increased more in RV (2.59%) than that in LV (2.21%). MMP-2 expression of the ND group in RV was significantly greater than the control and NS groups in RV and the corresponding ND group in LV. CONCLUSION: The experimental data support the hypothesis that ND administration induces greater MMP-2 expression increase in RV compared to LV, leading to consequent RV dilation.

Initial psychometric validation of the questionnaire on pain caused by spasticity (QPS).

BACKGROUND: The Questionnaire on Pain caused by Spasticity (QPS) is a modular patient- and observer-reported outcome measure of spasticity-related pain (SRP) in children with cerebral palsy (CP). Originally developed for an English-speaking population, we conducted a psychometric validation of a recently developed Chinese language version of the QPS. METHODS: This was a prospective, observational study involving 137 children/adolescents with CP and upper and/or lower limb spasticity and their parents at three sites in China. Six QPS modules were used, three each for upper and lower limb SRP assessment: a patient self-report module; an interviewer-administered module used by site staff based on the cognitive, communicative, and motor abilities of a patient; and a parent/caregiver module administered for all children as an observer-reported outcome to complement the patient-reported outcome. If no assessment by the patient was possible because of age or cognitive impairments, only the parent/caregiver module was completed. Two visits with a 3-week interval provided data to evaluate and establish administrative ease of use, scoring of the QPS (factor analyses, Rasch analyses), reliability (Cronbach's α, intraclass correlation coefficient), validity (correlations with quality of life [PedsQL™], motor impairment [Gross Motor Function Classification System, Gross Motor Function Measure-66, Manual Ability Classification System], and spasticity [Ashworth Scale, Modified Tardieu Scale]). RESULTS: For most children, clinic staff reported no difficulties associated with general QPS use or deciding which module to use. Children (and parents) who reported more demanding activities also reported higher levels of associated SRP (or observed SRP behavior). Activity-related SRP items were combined for a total QPS score. Cronbach's α was low for child self-report, but was acceptable for interviewer-administered and parent reports on SRP. Test-retest reliability was high for all modules. Moderate-strong associations were frequently seen between QPS and quality of life, and were particularly strong in the child self-report group. Relatively weak associations were observed between QPS and motor impairment and spasticity. CONCLUSIONS: This first study was successful in providing initial evidence for the psychometric properties. Clinic staff were able to administer the QPS modules easily, and both children and parents were able to complete the designated QPS appropriately.