The Streptococcus phage protein paratox is an intrinsically disordered protein.

The bacteriophage protein paratox (Prx) blocks quorum sensing in its streptococcal host by directly binding the signal receptor and transcription factor ComR. This reduces the ability of Streptococcus to uptake environmental DNA and protects phage DNA from damage by recombination. Past work characterizing the Prx:ComR molecular interaction revealed that paratox adopts a well-ordered globular fold when bound to ComR. However, solution-state biophysical measurements suggested that Prx may be conformationally dynamic. To address this discrepancy, we investigated the stability and dynamic properties of Prx in solution using circular dichroism, nuclear magnetic resonance, and several fluorescence-based protein folding assays. Our work shows that under dilute buffer conditions Prx is intrinsically disordered. We also show that the addition of kosmotropic salts or protein stabilizing osmolytes induces Prx folding. However, the solute stabilized fold is different from the conformation Prx adopts when it is bound to ComR. Furthermore, we have characterized Prx folding thermodynamics and folding kinetics through steady-state fluorescence and stopped flow kinetic measurements. Our results show that Prx is a highly dynamic protein in dilute solution, folding and refolding within the 10 ms timescale. Overall, our results demonstrate that the streptococcal phage protein Prx is an intrinsically disordered protein in a two-state equilibrium with a solute-stabilized folded form. Furthermore, the solute-stabilized fold is likely the predominant form of Prx in a solute-crowded bacterial cell. Finally, our work suggests that Prx binds and inhibits ComR, and thus quorum sensing in Streptococcus, by a combination of conformational selection and induced-fit binding mechanisms.

Matching-Adjusted Indirect Comparison of the Long-Term Efficacy of Deucravacitinib Versus Adalimumab for Moderate to Severe Plaque Psoriasis.

INTRODUCTION: Deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, is approved in the United States to treat adults with moderate-to-severe plaque psoriasis (PsO). This study compared the long-term efficacy of deucravacitinib and adalimumab using results from long-term extension (LTE) trials. METHODS: Open-label LTE trials were identified for an indirect treatment comparison (deucravacitinib: POETYK PSO-LTE [NCT04036435]; adalimumab: REVEAL extension [NCT00195676]). To ensure study design comparability, patients initially randomized to placebo and switched to deucravacitinib or adalimumab after week 16 were compared. The primary outcome was an ≥ 75% reduction in Psoriasis Area and Severity Index score (PASI 75) at week 112 postrandomization. Secondary outcomes were PASI 75 at week 52 and an ≥ 90% reduction in PASI score (PASI 90) at weeks 52 and 112. Missing PASI data were imputed. A matching-adjusted indirect comparison was conducted; individual patient-level data from POETYK PSO-LTE were reweighted to balance baseline characteristics with those from the REVEAL extension. RESULTS: Before reweighting, on average, patients in the POETYK PSO-LTE (N = 329) versus the REVEAL (N = 345) extension were older, had a lower body weight, received more prior systemic treatments, and had higher baseline PASI scores and week 16 placebo PASI 75 and PASI 90 response rates. Following reweighting, adjusted week 112 PASI 75 response rates were significantly higher for deucravacitinib versus adalimumab (67.2% vs. 54.0%; mean difference [95% CI], 13.2 [4.0-22.5] percentage points). Deucravacitinib had a numerically higher adjusted week 112 PASI 90 response rate (41.3% vs. 34.0%; mean difference [95% CI], 7.3 [-2.0 to 16.7] percentage points). The treatments had similar week 52 adjusted PASI 75 and PASI 90 response rates. CONCLUSION: In this interim analysis, adults with moderate to severe PsO had higher long-term response rates at 2 years when treated with deucravacitinib versus adalimumab. Deucravacitinib response rates remained stable whereas adalimumab response rates declined in year 2.

Plaque psoriasis is an inflammatory disease that causes red, itchy, dry patches (called plaques) on the skin. The disease cannot be cured, but the symptoms can be treated. Deucravacitinib and adalimumab are two treatments approved for use in adults with moderate to severe plaque psoriasis; deucravacitinib is an oral medication and adalimumab is injected with a needle under the skin. Each treatment has proven its efficacy compared with placebo (a pill or injection with no active effect) in separate clinical trials, but because no two clinical trials are exactly alike, the results cannot be accurately compared. Matching-adjusted indirect comparison is a method used to compare the results of one clinical trial with those of another when a direct comparison is not possible; characteristics from the patients in one trial are made to match the patient population in the other trial, and the adjusted results are compared. We performed a matching-adjusted indirect comparison of an open-label extension trial of deucravacitinib with an open-label extension trial of adalimumab to study the long-term efficacy of each treatment. At 1 year of treatment, we observed that similar proportions of patients receiving each treatment achieved a 75% or 90% improvement from their baseline Psoriasis Area and Severity Index score, called PASI 75 or PASI 90, respectively. At 2 years of treatment, similar proportions achieved PASI 90, but the proportion of patients receiving deucravacitinib who achieved PASI 75 was greater than that of patients receiving adalimumab.

Early Discontinuation of Apremilast in Patients with Psoriasis and Gastrointestinal Comorbidities: Rates and Associated Risk Factors.

INTRODUCTION: Apremilast, the first oral targeted treatment for moderate to severe psoriasis, is associated with diarrhea, nausea, and vomiting, which have contributed to treatment discontinuation. This study describes early apremilast discontinuation rates in patients with psoriasis, including a cohort with gastrointestinal (GI) comorbidities, and associated characteristics. METHODS: This retrospective cohort study used IBM® (now Merative™) MarketScan® commercial and Medicare claims data to identify adults with psoriasis who filled their first apremilast prescription between September 1, 2014 and March 31, 2020. Discontinuation was defined as a gap of > 30 days after exhausting the days' supply of a prescription fill. The GI comorbidity cohort included patients with ≥ 1 claim for inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), or other GI comorbidity during the study period. RESULTS: Discontinuation rates were high, regardless of previous biologic treatment or GI comorbidities. Among all patients, 25.5% discontinued within 60 days and 56.4% discontinued within 180 days. Patients who discontinued were more likely to be younger, female, and have IBD, Crohn's disease, or a mental health disorder. At 180 days, patients who used biologics previously were more likely to discontinue than biologic-naive patients. Patients with IBD discontinued at a greater rate than those without IBD at 60 days (30.3% vs 24.4%; P = 0.018) and 180 days (63.6% vs 57.2%; P = 0.026). Differences in discontinuation rates were minimal between GI comorbidity groups; patients with IBS discontinued at numerically higher rates than those without IBS. CONCLUSIONS: High rates of early discontinuation were observed for patients with and without GI comorbidities. Early discontinuation, whether attributable to poor tolerability or effectiveness, suggests the need for additional oral treatment options.

Treatment patterns and healthcare costs among patients with psoriasis initiating apremilast or biologics: a retrospective claims database cohort analysis.

OBJECTIVE: This study aimed to compare treatment patterns and healthcare costs for patients with psoriasis who initiate apremilast, tumor necrosis factor inhibitor, or interleukin inhibitor. METHODS: This retrospective cohort study used Optum Clinformatics® Data Mart to identify propensity score-matched patients initiating apremilast, tumor necrosis factor inhibitors, or interleukin inhibitors, with 12-month baseline and 24-month follow-up data. Switch, discontinuation, persistence, healthcare resource utilization, and total healthcare costs were assessed. RESULTS: Twenty-four-month switch rates were highest for tumor necrosis factor inhibitors (32%), followed by apremilast (21%) then interleukin inhibitors (14%). Mean (SD) per-patient-per-month costs for switchers were lowest for apremilast ($4213 [$2304]), higher for tumor necrosis factor inhibitors ($5274 [$2280]), and highest for interleukin inhibitors ($5539 [$2296]; p < .001), primarily attributable to pharmacy costs: $3466 (apremilast), $4432 (tumor necrosis factor inhibitor), and $4721 (interleukin inhibitor). LIMITATIONS: Psoriasis severity is absent from claims data; cost outcomes may be influenced by more severe psoriasis being more costly. CONCLUSION: Switching psoriasis treatment is common and increases over time. Apremilast initiators had lower switch rates and costs compared with tumor necrosis factor inhibitors, despite lower effectiveness reported in previous studies, perhaps indicating patient preference for oral treatment. Additional oral options may be desirable for this population.

Lovo-cel gene therapy for sickle cell disease: Treatment process evolution and outcomes in the initial groups of the HGB-206 study.

lovo-cel (bb1111; LentiGlobin for sickle cell disease [SCD]) gene therapy (GT) comprises autologous transplantation of hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified ß-globin gene (ßA-T87Q ) to produce anti-sickling hemoglobin (HbAT87Q ). The efficacy and safety of lovo-cel for SCD are being evaluated in the ongoing phase 1/2 HGB-206 study (ClinicalTrials.gov: NCT02140554). The treatment process evolved over time, using learnings from outcomes in the initial patients to optimize lovo-cel's benefit-risk profile. Following modest expression of HbAT87Q in the initial patients (Group A, n = 7), alterations were made to the treatment process for patients subsequently enrolled in Group B (n = 2, patients B1 and B2), including improvements to cell collection and lovo-cel manufacturing. After 6 months, median Group A peripheral blood vector copy number (≥0.08 c/dg) and HbAT87Q levels (≥0.46 g/dL) were inadequate for substantial clinical effect but stable and sustained over 5.5 years; both markedly improved in Group B (patient B1: ≥0.53 c/dg and ≥2.69 g/dL; patient B2: ≥2.14 c/dg and ≥6.40 g/dL, respectively) and generated improved biologic and clinical efficacy in Group B, including higher total hemoglobin and decreased hemolysis. The safety of the lovo-cel for SCD treatment regimen largely reflected the known side effects of HSPC collection, busulfan conditioning regimen, and underlying SCD; acute myeloid leukemia was observed in two patients in Group A and deemed unlikely related to insertional oncogenesis. Changes made during development of the lovo-cel treatment process were associated with improved outcomes and provide lessons for future SCD GT studies.

Health information seeking in the digital age: a national survey of women with disabilities.

PURPOSE: Access to high quality and accessible online health information (OHI) is critical for reducing disparities, overcoming barriers, and improving the health of women with disabilities. This study aimed to understand women with physical disabilities' use of the Internet to access OHI, most often searched health topics, perceived usefulness of OHI, and self-reported eHealth literacy and challenges in OHI seeking. METHODS: We conducted a national online survey with 508 women with physical disabilities who used the Internet. RESULTS: Respondents utilized a wide variety of OHI resources. They searched a broad array of health and disability-related topics, with bowel/bladder and finding a physician the most highly searched topics. They generally had confidence in their eHealth literacy skills and ability to understand statistics in OHI. Nevertheless, although our sample consisted of a majority of highly educated internet-users, a sizeable percentage found OHI seeking difficult and frustrating, did not find the information very helpful, and had concerns about the quality of information. CONCLUSIONS: This study serves as a call to action to disability and rehabilitation scientists, health care providers, and other health professionals to enhance the availability and accessibility of OHI critical to empowering women with physical disabilities to make well-informed health decisions. Implications for rehabilitationAccess to high quality online health information (OHI) is critical for reducing disparities, overcoming barriers, and improving the health of women with disabilities.Many of the women with disabilities in our study found OHI seeking difficult and frustrating, did not find the information very helpful, and had concerns about the quality of the information.Disability and rehabilitation scientists, health care providers, and public health and health policy professionals need to do more to enhance the availability and accessibility of OHI and resources critical to empowering women with physical disabilities to make well-informed health decisions.Physical medicine and rehabilitation scientists are encouraged to develop and improve assistive technologies needed for accessing OHI, which in turn can promote the independent functioning of people with disabilities.

Does Urea Preferentially Interact with Amide Moieties or Nonpolar Sidechains? A Question Answered Through a Judicious Selection of Model Systems.

The transfer model suggests that urea unfolds proteins mainly by increasing the solubility of the amide backbone, probably through urea-induced increase in hydrogen bonding. Other studies suggest that urea addition increases the magnitude of solvent-solute van der Waals interactions, which increases the solubility of nonpolar sidechains. More recent analyses hypothesize that urea has a similar effect in increasing the solubility of backbone and sidechain groups. In this work, we compare the effects of urea addition on the solvation of amides and alkyl groups. At first, we study the effects of urea addition upon solvent hydrogen bonding acidity and basicity through the perturbation in the fluorescence spectrum of probes 1-AN and 1-DMAN. Our results demonstrate that the solvent's hydrogen bonding properties are minimally affected by urea addition. Subsequently, we show that urea addition does not perturb the intra-molecular hydrogen bonding in salicylic acid significantly. Finally, we investigate how urea preferentially interacts with amide and alkyl groups moieties in water by comparing the effects of urea addition upon the solubility of acetaminophen and 4-tertbutylphenol. We show that urea affects amide and t-butyl solubility (lowers the transfer free energy of both amide (backbone) and alkyl (sidechain) groups) in a similar fashion. In other words, preferential interaction of urea with both moieties contributes to protein denaturation.

Economic Burden of Comorbidities in Patients with Psoriasis in the USA.

INTRODUCTION: This study assessed the comorbidity burden, healthcare resource utilization (HCRU), and costs associated with patients with moderate to severe psoriasis (PsO) compared with a matched cohort of the general population without PsO in the USA. METHODS: Comorbidity-related HCRU (incidence rate ratios [IRRs]) and direct medical cost burden (per patient per month [PPPM] 2020 USD) in patients with moderate to severe PsO in the USA, previously apremilast- and biologic-naive, but currently treated, versus the general population were assessed through a retrospective cohort study using IBM (now Merative) MarketScan Commercial and Medicare Claims data (1 January 2006 to 31 December 2019). Comorbidities included cardiovascular, mental health, pulmonary, diabetes, hyperlipidemia, hypertension, peripheral vascular, liver, obesity, and other autoimmune disorders. RESULTS: There are increased all-cause HCRU and costs in patients with PsO compared with the general population. These differences (PsO-general population) in HCRU and costs (IRR visits; PPPM) are associated with specific comorbidities, including mental health (1.08; $372), chronic pulmonary disease (1.07; $135), diabetes (1.10; $159), hyperlipidemia (1.13; $203), hypertension (1.13; $305), liver disease (1.21; $360), and obesity (1.12; $145, all P < 0.01). CONCLUSIONS: Patients with PsO experience a higher economic burden of comorbidities than the general population despite using currently available systemic treatments for PsO.

Psoriasis is a disease that causes itchy and painful sores on the skin. People with psoriasis can develop several other diseases, known as comorbidities. These comorbidities include cardiovascular disease, depression, diabetes, hypertension, and obesity, and they pose a large economic burden to individuals, households, and society. Existing estimates of this burden are outdated because new treatments have become available for psoriasis. The aim of this study was to assess the economic burden of comorbidities in people with psoriasis compared with the economic burden in the general population in the USA. Healthcare claims reported in the IBM (now Merative) MarketScan Commercial and Medicare Claims database were used. This study assessed the total number of health-related visits to a doctor's office, hospital, or emergency department and the total costs of these visits in both groups. This study found that people with psoriasis had more health visits and costs because of comorbidities than the general population, despite using advanced treatments for their psoriasis.

Innovative treatment utilizing an autologous blood clot for diabetic foot ulcers.

INTRODUCTION: Diabetic foot ulcer is a complex wound that requires considerable effort to restart a stalled healing process. In this study, a TABCT product was used in a point-of-care setting to treat DFUs by reconstructing the ECM and adjusting intricate phenotypes and mechanisms of mediators to progress towards complete healing. The mechanism of action consists of reconstruction of the ECM, which protects the wound area from further destruction while it incorporates into the ulcer to promote granulation over exposed vital structures (ie, tendons, bone, and neurovascular structures). OBJECTIVE: The authors evaluated the efficacy of the TABCT product in the management of DFUs. MATERIALS AND METHODS: Study participants were wound care patients in hospitals and clinics across the United States and Israel as part of a registry study (ClinicalTrials.gov: NCT04699305). Twenty-nine patients age 18 years or older with chronic DFUs were included. A blood clot was created using the patient's own peripheral blood in a point-of-care setting. An 18-mL blood sample was drawn from the patient and incorporated with calcium gluconate and kaolin to form a clot. Efficacy and superiority levels in PAR at week 4 and week 12 over the SOC treatment were established using the Agresti-Coull confidence interval. RESULTS: Treatment of DFUs using the TABCT product resulted in 22 patients (75.86%) achieving 50% PAR at week 4 and showed superiority when compared with SOC data in previously published studies. Complete closure was achieved in 28 wounds (95%) at week 12. CONCLUSION: In the current study, TABCT exhibited superiority over SOC treatment and provided granulation over vital structures with a reduction in overall wound size in a timely manner via incorporation and stimulation of the body's own healing capabilities.

Shock Tube/Laser Absorption Measurements of Cyclopentadiene Pyrolysis.

High-temperature cyclopentadiene pyrolysis was examined behind reflected shock waves in a heated shock tube using several laser absorption diagnostic schemes. A two-color, online-offline sensor near 3335 cm-1 was used to measure time histories of acetylene, while a three-color scheme of diagnostics at 10.532, 10.675, and 11.345 µm yielded measurements of cyclopentadiene and ethylene. Species time histories of cyclopentadiene decomposition and acetylene formation as well as ethylene yields are reported from 1319 to 1678 K at 1.2-1.5 atm. In addition, the overall decomposition rate of cyclopentadiene is reported, and comparisons are made to a number of kinetic models.

Development of a novel PRO instrument for use in familial chylomicronemia syndrome.

BACKGROUND: Familial chylomicronemia syndrome (FCS), a rare genetic disorder characterized by high levels of circulating triglycerides, negatively impacts multiple organs, including the liver and pancreas. OBJECTIVE: The objective of this study was to develop and support the content validity of a novel patient-reported outcome (PRO) measure addressing FCS symptoms and impacts. To facilitate use in clinical trials of new treatments, evidence supporting the new measure needed to be consistent with regulatory guidance and requirements. METHODS: A pool of items addressing symptoms and impacts of FCS was initially developed based on data from a large burden-of-illness study with patients with FCS as well as a review of available literature and existing PRO measures. Two rounds of qualitative interviews were conducted with patients with FCS (N = 10) to refine the draft items and support the measure's content validity. Each interview began with concept elicitation followed by cognitive debriefing of the draft FCS measure. RESULTS: Patient-reported symptoms and impacts of FCS were generally consistent with those identified by the burden-of-illness study; abdominal pain was particularly prevalent and salient for patients. Suggested changes to the draft item pool were generally minor. Comprehensibility and ease of completion for the final instrument were confirmed during the second set of interviews. CONCLUSION: The content validity of the final 17-item FCS Symptoms and Impacts Scale is strongly supported by patient input gathered through both a large burden-of-illness study and qualitative research. To further support use in clinical trials, psychometric evaluation of the measure is underway.

Collisional excitation kinetics for O(3s

Collisional excitation kinetics for atomic oxygen is studied behind reflected shock waves in 1%O_{2}/Ar mixtures over 10 000-11 000K using laser absorption spectroscopy of the O(3s^{5}S^{o}) to O(3p^{5}P_{3}) transition at 777 nm and the O(3p^{5}P_{3}) to O(3d ^{5}D_{2,3,4}^{o}) transitions at 926 nm. Four time histories are inferred simultaneously from the absorbance of the two transitions: the population density of level 4 of atomic oxygen, i.e., the O(3s ^{5}S^{o}) state, n_{4}; the population density of level 6 of atomic oxygen, i.e., the O(3p^{5}P_{3}) state, n_{6}; the electron number density, n_{e}; and the heavy-particle translational temperature, T_{tr}. Atomic oxygen in the levels 4 and 6 are not in equilibrium with the ground-state atomic oxygen as the measurements of n_{4} and n_{6} are generally 3-20 times smaller than the corresponding values under Boltzmann equilibrium at T_{tr}. However, these two states are close to partial equilibrium with each other within the test time, indicating strong heavy-particle cross coupling between levels 4 and 6 of atomic oxygen. A simplified two-temperature collisional-radiative (CR) model is developed to study the thermal and chemical nonequilibrium of atomic oxygen following shock heating. The four measured time histories are used to optimize the 12 collisional rate constants in the CR model using a stochastic gradient descent (SGD) algorithm. The time-history results, diagnostic methods, and collisional-radiative model presented in the current study are potentially useful in studies of high-enthalpy air, plasma processing, or other applications involving weakly ionized oxygen.

Boron rich nanotube drug carrier system is suited for boron neutron capture therapy.

Boron neutron capture therapy (BNCT) is a two-step therapeutic process that utilizes Boron-10 in combination with low energy neutrons to effectively eliminate targeted cells. This therapy is primarily used for difficult to treat head and neck carcinomas; recent advances have expanded this method to cover a broader range of carcinomas. However, it still remains an unconventional therapy where one of the barriers for widespread adoption is the adequate delivery of Boron-10 to target cells. In an effort to address this issue, we examined a unique nanoparticle drug delivery system based on a highly stable and modular proteinaceous nanotube. Initially, we confirmed and structurally analyzed ortho-carborane binding into the cavities of the nanotube. The high ratio of Boron to proteinaceous mass and excellent thermal stability suggest the nanotube system as a suitable candidate for drug delivery into cancer cells. The full physicochemical characterization of the nanotube then allowed for further mechanistic molecular dynamic studies of the ortho-carborane uptake and calculations of corresponding energy profiles. Visualization of the binding event highlighted the protein dynamics and the importance of the interhelical channel formation to allow movement of the boron cluster into the nanotube. Additionally, cell assays showed that the nanotube can penetrate outer membranes of cancer cells followed by localization around the cells' nuclei. This work uses an integrative approach combining experimental data from structural, molecular dynamics simulations and biological experiments to thoroughly present an alternative drug delivery device for BNCT which offers additional benefits over current delivery methods.

Efficacy of aminolevulinic acid 20 % solution photodynamic therapy in the treatment of actinic keratoses on the upper extremities: A post hoc analysis of a phase 3, randomized, vehicle-controlled trial.

BACKGROUND: Photodynamic therapy with 5-aminolevulinic acid is indicated for targeted treatment of actinic keratoses on the face, scalp, and upper extremities. This was a post hoc analysis of a phase 3 randomized trial assessing the efficacy of aminolevulinic acid/photodynamic therapy for treatment of actinic keratoses on the upper extremities. METHODS: Adults with 4-15 grade 1-2 actinic keratosis lesions on ≥1 upper extremity were randomized (1:1) to receive aminolevulinic acid/photodynamic therapy or vehicle/photodynamic therapy applied to individual lesions followed by occlusion and blue light treatment. Assessments included the clearance rate of treated lesions vs baseline, cumulative disease area clearance, and complete clearance by lesion size. RESULTS: There were 135 and 134 patients randomized to aminolevulinic acid/photodynamic therapy and vehicle/photodynamic therapy groups, respectively. At 12 weeks, clearance of treated lesions (80.6 % vs 45.5 %; P <0.0001) and the mean decrease in cumulative disease area (82.4 % vs 42.6 %; P <0.0001) was significantly higher for aminolevulinic acid/photodynamic therapy vs vehicle/photodynamic therapy, respectively. Rates of complete clearance and clearance by cutpoint (≥90 %, ≥85 %, ≥80 %, or ≥75 % clearance) were numerically higher for aminolevulinic acid/photodynamic therapy. Clearance of lesions was higher for aminolevulinic acid/photodynamic therapy vs vehicle/photodynamic therapy regardless of baseline lesion size. Aminolevulinic acid/photodynamic therapy was well tolerated with adverse events consistent with those expected with photodynamic therapy. CONCLUSIONS: Aminolevulinic acid photodynamic therapy is effective and well tolerated for the treatment of actinic keratosis lesions of the extremities.

2D Saturation Transfer Difference NMR for Determination of Protein Binding Sites on RNA Guanine Quadruplexes.

Saturation transfer difference (STD) NMR is a technique that provides information on the intermolecular interfaces of heterogenous complexes by cross-saturation from one molecule to the other. In this case, selective saturation of protein protons is applied, and the cross-relaxation to the RNA sample results in a reduction of the peak intensities in the measured H1-H1 NOESY spectrum. This allows for a relatively rapid and simple method of identifying the protein binding interface of an RNA with assigned chemical shift data.

Ketogenic, Hypocaloric Diet Improves Nonalcoholic Steatohepatitis.

BACKGROUND AND OBJECTIVES: Nonalcoholic steatohepatitis (NASH) is strongly associated with obesity. A weight loss of ≥10% is necessary to improve NASH severity, but this goal has rarely been achieved in published studies using different diet protocols. The effect of a ketogenic, hypocaloric, commercial diet ("Ideal Protein," IP) on body weight, metabolic markers, and liver tests in a group of NASH patients is evaluated in this study. Daily calorie intake was tailored to achieve a weight loss of ≥10%. METHODS: We analyzed 38 patients with NASH who were placed on the IP diet between 2014 and 2018 and compared their outcomes with 6 control patients who declined the diet. All patients were evaluated by a trained health coach in weekly intervals throughout the study period. Clinical and laboratory data obtained before and at 6.5 months after intervention were compared using paired t-testing. RESULTS: The patients on the IP diet experienced a significant weight reduction (217 ± 8 lb vs. 194 ± 7 lb; mean ± S.E.M.), corresponding to an average weight loss of 9.7% ± 1.6%. Significant changes in systolic blood pressure (133 ± 3 mmHg vs. 123 ± 3 mmHg), triglycerides (200 ± 21 mmol/L vs. 132 ± 11 mmol/L), hemoglobin A1c (6.71% ± 0.29% vs. 5.74% ± 0.19%), SGPT (97.3 ± 11.1 IU/L vs. 44.2 ± 5.9 IU/L), SGOT (82.4 ± 10.5 IU/L vs. 32.8 ± 5.2 IU/L), and Fib-4 scores (2.25 ± 0.23 vs. 1.40 ± 0.13) were also observed (P<0.05 in all cases). In the IP group, 50.5% of patients lost ≥10% body weight. In contrast, no significant changes were observed in the control group. The IP diet was well tolerated, and no safety signals were noticed. CONCLUSIONS: A ketogenic, hypocaloric resulted in striking weight loss and significant improvements in metabolic parameters and liver tests, suggesting that this approach carries promise for the dietary management of patients with NASH.

Determination of the JP10 + OH → Product Reaction Rate with Measured Fuel Concentrations in Shock Tube Experiments.

The overall reaction rate for JP10 + OH → products was measured directly via laser absorption of OH in shock tube experiments from 931 to 1308 K and 0.94 to 1.44 atm. The JP10 concentration of test gas mixtures was measured in the shock tube for several experiments using a 3.39 µm laser fuel diagnostic. The measured JP10 concentrations indicated fuel losses due to adsorption of 11-31% compared to values calculated manometrically from mixture preparation. OH was generated via rapid thermal decomposition of tert-butyl hydroperoxide behind reflected shock waves, and post-shock OH profiles were measured via laser absorption at 308.6 nm. The measured OH profiles were fit with a chemical kinetic model for JP10 chemistry to determine the overall JP10 + OH reaction rate. A recommendation is made for the JP10 + OH overall reaction rate over the temperature range explored in this study as k1 (931-1308 K) = 1.622 × 1014 exp(-1826/T [K]) ± 12%. To the authors' knowledge, these data are the first direct measurements of the overall reaction rate for JP10 + OH.

Shock Tube Measurement of the CH3 + C2H6 → CH4 + C2H5 Rate Constant.

The rate constant for the CH3 + C2H6 → CH4 + C2H5 reaction was studied behind reflected shock waves at temperatures between 1369 and 1626 K and pressures from 8.6 to 47.4 atm in mixtures of methane, ethane, and argon. Ethylene time histories were measured using laser absorption of radiation from a carbon dioxide gas laser near 10.532 µm. The resulting rate constant data can be represented by the Arrhenius equation k (T) = 3.90 × 1013 exp(-16670 cal/mol/RT) cm3 mol-1 s-1. We believe this is the first study to extend experimental data for this rate constant to temperatures above 1400 K. The overall 2σ uncertainty of the current data is +18%/-21% resulting primarily from uncertainties associated with the influence of secondary reactions and the fitting of rapidly changing species time histories at the higher temperatures.