Closing Dichloramine Decomposition Nitrogen and Oxygen Mass Balances: Relative Importance of End-Products from the Reactive Nitrogen Species Pathway.

In drinking water chloramination, monochloramine autodecomposition occurs in the presence of excess free ammonia through dichloramine, the decay of which was implicated in N-nitrosodimethylamine (NDMA) formation by (i) dichloramine hydrolysis to nitroxyl which reacts with itself to nitrous oxide (N2O), (ii) nitroxyl reaction with dissolved oxygen (DO) to peroxynitrite or mono/dichloramine to nitrogen gas (N2), and (iii) peroxynitrite reaction with total dimethylamine (TOTDMA) to NDMA or decomposition to nitrite/nitrate. Here, the yields of nitrogen and oxygen-containing end-products were quantified at pH 9 from NHCl2 decomposition at 200, 400, or 800 µeq Cl2·L-1 with and without 10 µM-N TOTDMA under ambient DO (∼500 µM-O) and, to limit peroxynitrite formation, low DO (≤40 µM-O). Without TOTDMA, the sum of free ammonia, monochloramine, dichloramine, N2, N2O, nitrite, and nitrate indicated nitrogen recoveries ±95% confidence intervals were not significantly different under ambient (90 ± 6%) and low (93 ± 7%) DO. With TOTDMA, nitrogen recoveries were less under ambient (82 ± 5%) than low (97 ± 7%) DO. Oxygen recoveries under ambient DO were 88-97%, and the so-called unidentified product of dichloramine decomposition formed at about three-fold greater concentration under ambient compared to low DO, like NDMA, consistent with a DO limitation. Unidentified product formation stemmed from peroxynitrite decomposition products reacting with mono/dichloramine. For a 2:2:1 nitrogen/oxygen/chlorine atom ratio and its estimated molar absorptivity, unidentified product inclusion with uncertainty may close oxygen recoveries and increase nitrogen recoveries to 98% (ambient DO) and 100% (low DO).

Who Gets Sick From COVID-19? Sociodemographic Correlates of Severe Adult Health Outcomes During Alpha- and Delta-Variant Predominant Periods: September 2020-November 2021.

BACKGROUND: Because COVID-19 case data do not capture most SARS-CoV-2 infections, the actual risk of severe disease and death per infection is unknown. Integrating sociodemographic data into analysis can show consequential health disparities. METHODS: Data were merged from September 2020 to November 2021 from 6 national surveillance systems in matched geographic areas and analyzed to estimate numbers of COVID-19-associated cases, emergency department visits, and deaths per 100 000 infections. Relative risks of outcomes per infection were compared by sociodemographic factors in a data set including 1490 counties from 50 states and the District of Columbia, covering 71% of the US population. RESULTS: Per infection with SARS-CoV-2, COVID-19-related morbidity and mortality were higher among non-Hispanic American Indian and Alaska Native persons, non-Hispanic Black persons, and Hispanic or Latino persons vs non-Hispanic White persons; males vs females; older people vs younger; residents in more socially vulnerable counties vs less; those in large central metro areas vs rural; and people in the South vs the Northeast. DISCUSSION: Meaningful disparities in COVID-19 morbidity and mortality per infection were associated with sociodemography and geography. Addressing these disparities could have helped prevent the loss of tens of thousands of lives.

Long-term Outcomes of Chemoradiation for Muscle-invasive Bladder Cancer in Noncystectomy Candidates. Final Results of NRG Oncology RTOG 0524-A Phase 1/2 Trial of Paclitaxel + Trastuzumab with Daily Radiation or Paclitaxel Alone with Daily Irradiation.

BACKGROUND: Chemo-radiation is a well-established alternative to radical cystectomy in patients with muscle-invasive bladder cancer. Many patients due to age or medical comorbidity are unfit for either radical cystectomy, or standard cisplatin- or 5-fluorouracil-based chemoradiation, and do not receive appropriate treatment with curative intent. We treated patients with a less aggressive protocol employing seven weekly doses of paclitaxel and daily irradiation. In those whose tumors showed overexpression of her2/neu, seven weekly doses of trastuzumab were also administered. OBJECTIVE: To report the long-term survival outcomes and toxicity results of the of NRG Oncology RTOG 0524 study. DESIGN, SETTING, AND PARTICIPANTS: Seventy patients were enrolled and 65 (median age: 76 yr) were deemed eligible. Patients were assigned to daily radiation and weekly paclitaxel + trastuzumab (group 1, 20 patients) or to daily radiation plus weekly paclitaxel (group 2, 45 patients) based on tumor her2/neu overexpression. Radiation was delivered in 1.8 Gy fractions to a total dose of 64.8 Gy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was unresolved treatment-related toxicity. The secondary endpoints were complete response rate, protocol completion rate, and disease-free and overall survival. RESULTS AND LIMITATIONS: Protocol therapy was completed by 60% (group 1) and 76% (group 2); complete response rates at 12 wk were 62% in each group. Acute treatment-related adverse events (AEs) of grade ≥3 were observed in 80% in group 1 and 58% in group 2. There was one treatment-related grade 5 AE in group 1. Unresolved acute treatment-related toxicity was 35% in group 1 and 31% in group 2. The median follow-up was 2.3 yr in all patients and 7.2 yr in surviving patients. Overall survival at 5 yr was 25.0% in group 1 and 37.8% in group 2 (33.8% overall). At 5 yr, disease-free survival was 15.0% in group 1 and 31.1% in group 2. CONCLUSIONS: In a cohort of patients with muscle-invasive bladder cancer who are not candidates for cystectomy or cisplatin chemotherapy, chemoradiation therapy offers a treatment with a significant response rate and 34% 5-yr overall survival. While there were many AEs in this medically fragile group, there were few grade 4 events and one grade 5 event attributable to therapy. PATIENT SUMMARY: Patients with invasive bladder cancer who cannot tolerate surgery were treated with radiation and systemic therapy without surgically removing their bladders. Most patients tolerated the treatment, were able to keep their bladders, and showed a significant treatment response rate.

The circular bacteriocin enterocin NKR-5-3B has an improved stability profile over nisin.

Bacteriocins are a large family of bacterial peptides that have antimicrobial activity and potential applications as clinical antibiotics or food preservatives. Circular bacteriocins are a unique class of these biomolecules distinguished by a seamless circular topology, and are widely assumed to be ultra-stable based on this constraining structural feature. However, without quantitative studies of their susceptibility to defined thermal, chemical, and enzymatic conditions, their stability characteristics remain poorly understood, limiting their translational development. Here, we produced the circular bacteriocin enterocin NKR-5-3B (Ent53B) in mg/L quantities using a heterologous Lactococcus expression system, and characterized its thermal stability by NMR, chemical stability by circular dichroism and analytical HPLC, and enzymatic stability by analytical HPLC. We demonstrate that Ent53B is ultra-stable, resistant to temperatures approaching boiling, acidic (pH 2.6) and alkaline (pH 9.0) conditions, the chaotropic agent 6 M urea, and following incubation with a range of proteases (i.e., trypsin, chymotrypsin, pepsin, and papain), conditions under which most peptides and proteins degrade. Ent53B is stable across a broader range of pH conditions and proteases than nisin, the most widely used bacteriocin in food manufacturing. Antimicrobial assays showed that differences in stability correlated with differences in bactericidal activity. Overall, this study provides quantitative support for circular bacteriocins being an ultra-stable class of peptide molecules, suggesting easier handling and distribution options available to them in practical applications as antimicrobial agents.

Non-Steady-State Fickian Diffusion Models Decrease the Estimated Gel Layer Diffusion Coefficient Uncertainty for Diffusive Gradients in Thin-Films Passive Samplers.

Mass transport in diffusive gradients in thin-film passive samplers is restricted to diffusion through a gel layer of agarose or agarose cross-linked polyacrylamide (APA). The gel layer diffusion coefficient, DGel, is typically determined using a standard analysis (SA) based on Fick's first law from two-compartment diffusion cell (D-Cell) tests. The SA assumes pseudo-steady-state flux, characterized by linear sink mass accumulation-time profiles with a typical threshold R2 ≥ 0.97. In 72 D-Cell tests with nitrate, 63 met this threshold, but the SA-determined DGel ranged from 10.1 to 15.8 × 10-6 cm2·s-1 (agarose) and 9.5 to 14.7 × 10-6 cm2·s-1 (APA). A regression model developed with the SA to account for the diffusive boundary layer had 95% confidence intervals (CIs) on DGel of 13 to 18 × 10-6 cm2·s-1 (agarose) and 12 to 19 × 10-6 cm2·s-1 (APA) at 500 rpm. A finite difference model (FDM) developed based on Fick's second law with non-steady-state (N-SS) flux decreased uncertainty in DGel tenfold. The FDM-captured decreasing source compartment concentrations and N-SS flux in the D-Cell tests and, at 500 rpm, the FDM-determined DGel ± 95% CIs were 14.5 ± 0.2 × 10-6 cm2·s-1 (agarose) and 14.0 ± 0.3 × 10-6 cm2·s-1 (APA), respectively.

An acetonic extract and secondary metabolites from the endolichenic fungus Nemania sp. EL006872 exhibit immune checkpoint inhibitory activity in lung cancer cell.

Background: Endolichenic fungi (ELF), which live the inside the lichen thallus, contain many secondary metabolites that show various biological activities. Recent studies show that lichen and ELF secondary metabolites have antioxidant, antibacterial, antifungal, cytotoxic, and anticancer activities. Purpose: Here, the effects of an ELF extract and its bioactive compounds were investigated on the H1975 cell line focusing on immune checkpoint marker inhibition. Methods: An ELF was isolated from the host lichen Bryoria fuscescens (Gyelnik) Brodo and D. Hawksw and identified the species as Nemania sp. EL006872. The fungus was cultured on agar medium and acetonic extracts were obtained. Secondary metabolites radianspenes C and D, and dahliane D, were isolated from the crude extract. The biological effects of both the crude extract and the isolated secondary metabolites were evaluated in cell viability, qRT-PCR assays, flow cytometry analysis and western blotting. Results: The cell viability assay revealed that extracts from Nemania sp. EL006872 and the isolated secondary compounds had low cytotoxicity. The crude extract, radianspenes C and D, and dahliane D, suppressed expression of mRNA encoding PD-L1 and aromatic hydrocarbon receptor (AhR), and surface expression of PD-L1 protein by cells exposed to benzo[a] pyrene. Radianspenes C and D, and dahliane D, reduced expression of AhR, PD-L1, ICOSL, and GITRL proteins by H1975 lung cancer cells, as well as exerting anti-proliferative effects. Conclusion: Radianspenes C and D, and dahliane D, bioactive compounds isolated from Nemania sp. EL006872 ELF, have the potential for use as immunotherapy and immunoncology treatments.

Contemporary, national patterns of surgery after preoperative therapy for stage II/III rectal adenocarcinoma.

BACKGROUND: Contemporary treatment of stage II/III rectal cancer combines chemotherapy, chemoradiation, and surgery, though the sequence of surgery with neoadjuvant treatments and benefits of minimally-invasive surgery (MIS) is debated. AIM: To describe patterns of surgical approach for stage II/III rectal cancer in relation to neoadjuvant therapies. METHODS: A retrospective cohort was created using the National Cancer Database. Primary outcome was rate of sphincter-sparing surgery after neoadjuvant therapy. Secondary outcomes were surgical approach (open, laparoscopic, or robotic), surgical quality (R0 resection and 12+ lymph nodes), and overall survival. RESULTS: A total of 38927 patients with clinical stage II or III rectal adenocarcinoma underwent surgical resection from 2010-2016. Clinical stage II patients had neoadjuvant chemoradiation less frequently compared to stage III (75.8% vs 84.7%, P < 0.001), but had similar rates of total neoadjuvant therapy (TNT) (27.0% vs 27.2%, P = 0.697). Overall rates of total mesorectal excision without sphincter preservation were similar between clinical stage II and III (30.0% vs 30.3%) and similar if preoperative treatment was chemoradiation (31.3%) or TNT (30.2%). Over the study period, proportion of cases approached laparoscopically increased from 24.9% to 32.5% and robotically 5.6% to 30.7% (P < 0.001). This cohort showed improved survival for MIS approaches compared to open surgery (laparoscopy HR 0.85, 95%CI 0.78-0.93, and robotic HR 0.82, 95%CI 0.73-0.92). CONCLUSION: Sphincter preservation rates are similar across stage II and III rectal cancer, regardless of delivery of preoperative chemotherapy, chemoradiation, or both. At a national level, there is a shift to predominantly MIS approaches for rectal cancer, regardless of whether sphincter sparing procedure is performed.

The Distribution of Dengue Virus Serotype in Quang Nam Province (Vietnam) during the Outbreak in 2018.

Objectives: Quang Nam province in the Centre of Vietnam has faced an outbreak of dengue hemorrhagic fever (DHF) in 2018. Although DHF is a recurrent disease in this area, no epidemiological and microbiological reports on dengue virus serotypes have been conducted mainly due to lack of facilities for such a kind of advanced surveillance. The aim of this study was to detect different dengue virus serotypes in patients' blood samples. Design and Methods: Suspected cases living in Quang Nam province (Vietnam) and presenting clinical and hematological signs of dengue hemorrhagic fever were included in the study. The screening was performed, and the results were compared by using two methodologies: RT real-time PCR (RT-rPCR) and the Dengue NS1 rapid test. Results: From December 2018 to February 2019, looking both at RT-rPCR [+] and NS1 [+] methodologies, a total of 488 patients were screened and 336 were positive for dengue virus detection (74 children and 262 adults); 273 of these patients (81.3%) underwent viral serotype identification as follows: 12.82% (35/273) D1 serotype, 17.95% (49/273) D2, 0.37% (1/273) D3, 68.50 (187/283) D4, and 0.37% (1/273) D2+D4 serotypes. The RT-rPCR outcomes showed higher sensitivity during the first three days of infection compared to NS1 (92.3% vs. 89.7%). The NS1 increased sensitivity after the first 3 days whilst the RT-rPCR decreased. Conclusions: Advanced surveillance with dengue virus serotypes identification, if performed routinely, may help to predict and prevent further DHF epidemics based on the exposure of the different serotypes during different periods that lead to the intensification of disease severity as a consequence of antibody-dependent enhancement (ADE).

Cyclohumulanoid Sesquiterpenes Induced by the Noncompetitive Coculture of Phellinus orientoasiaticus and Xylodon flaviporus.

Microbial cocultivation has been applied as a strategy to induce the biosynthesis of specialized metabolites. However, most previous studies have focused on competitive interactions between test strains. During our LC-MS-based chemical screening of randomized cocultures of Basidiomycetous fungi, we discovered that the coculture of Phellinus orientoasiaticus (Hymenochaetaceae) and Xylodon flaviporus (Schizoporaceae) induces multiple metabolites, although they did not show any competitive morphology. Targeted isolation yielded three new sesquiterpenes (1-3) along with five known analogues (4-8). The structures of the isolates were determined by MS and NMR experiments as well as electronic circular dichroism analysis. LC-MS analysis suggested that cyclohumulanoids of illudane-, sterpurane-, and tremulane-type scaffolds (1-7) were produced by P. orientoasiaticus, whereas a drimane-type sesquiterpene (8) was produced by X. flaviporus. None of the isolates exhibited antifungal activity or cytotoxicity, and compounds 1-7 exhibited NO production of LPS-treated RAW276.4 cells in a range of 15.9% to 38.0% at 100 µM.

Toxicity After Stereotactic Body Radiation Therapy for Prostate Cancer in Patients With Inflammatory Bowel Disease: A Multi-institutional Matched Case-Control Series.

PURPOSE: To evaluate the safety of stereotactic body radiation therapy (SBRT) for prostate cancer in men with inflammatory bowel disease (IBD). METHODS AND MATERIALS: We queried a consortium database for patients with IBD receiving SBRT for prostate cancer between 2006 and 2012. Identified patients were matched with patients without a history of IBD in a 3:1 fashion based on dose, fractionation, use of androgen deprivation therapy, and age distribution. Logistic regression was used to evaluate the association between having IBD and experiencing acute and late gastrointestinal (GI) and genitourinary (GU) toxicities as scored on the Common Terminology Criteria for Adverse Events scale. Time to late toxicity was evaluated using proportional hazard Cox models. Our study was limited by absence of data on prostate size, baseline International Prostate Symptom Score, and rectal dose-volume histogram parameters. RESULTS: Thirty-nine patients with flare-free IBD at time of treatment (median follow-up 83.9 months) and 117 matched controls (median follow-up 88.7 months) were identified. A diagnosis of IBD was associated with increased odds of developing any late grade GI toxicity (odds ratio [OR] 6.11, P <.001) and GU toxicity (odds ratio 6.14, P < .001), but not odds of developing late grade ≥2 GI (P = .08) or GU toxicity (P = .069). Acute GI and GU toxicity, both overall and for grade ≥2 toxicities, were more frequent in men with IBD (P < .05). Time to late GI and GU toxicity of any grade was significantly shorter in patients with IBD (P < .001). Time to late grade ≥2 GU, but not grade ≥2 GI toxicity, was also shorter in patients with IBD (P = .044 for GU and P = .144 for GI). CONCLUSIONS: Patients with IBD who received SBRT for PCa had a higher likelihood of developing acute GI and GU toxicity, in addition to experiencing lower grade late toxicities that occurred earlier. However, patients with IBD did not have a higher likelihood for late grade ≥2 GI or GU toxicity after SBRT compared with the control cohort. Interpretation of this data are limited by the small sample size. Thus, men with IBD in remission should be properly counseled about these risks when considering SBRT.

Pediatricians' Knowledge and Practices Related to Mumps Diagnosis and Prevention.

OBJECTIVES: To assess pediatricians' mumps knowledge and testing practices, to identify physician and practice characteristics associated with mumps testing practices, and to assess reporting and outbreak response knowledge and practices. STUDY DESIGN: Between January and April 2020, we surveyed a nationally representative network of pediatricians. Descriptive statistics were generated for all items. The χ2 test, t tests, and Poisson regression were used to compare physician and practice characteristics between respondents who would rarely or never versus sometimes or often/always test for mumps in a vaccinated 17-year-old with parotitis in a non-outbreak setting. RESULTS: The response rate was 67% (297 of 444). For knowledge, more than one-half of the pediatricians responded incorrectly or "don't know" for 6 of the 9 true/false statements about mumps epidemiology, diagnosis, and prevention, and more than one-half reported needing additional guidance on mumps buccal swab testing. For testing practices, 59% of respondents reported they would sometimes (35%) or often/always (24%) test for mumps in a vaccinated 17-year-old with parotitis in a non-outbreak setting; older physicians, rural physicians, and physicians from the Northeast or Midwest were more likely to test for mumps. Thirty-six percent of the pediatricians reported they would often/always report a patient with suspected mumps to public health authorities. CONCLUSIONS: Pediatricians report mumps knowledge gaps and practices that do not align with public health recommendations. These gaps may lead to underdiagnosis and underreporting of mumps cases, delaying public health response measures and contributing to ongoing disease transmission.

Potential of 1H NMR fingerprinting and a model system approach to study non-enzymatic browning in shelf-stable orange juice during storage.

For the first time, a model system approach was combined with 1H NMR fingerprinting in studying non-enzymatic browning (NEB) of pasteurized shelf-stable orange juice during storage. Various NEB precursors were used individually or in combinations to formulate simple or complex model systems, respectively, in citric acid buffer. Based on orange juice composition, ascorbic acid, sugars (sucrose, glucose and fructose) and amino acids (proline, arginine, asparagine, aspartic acid, serine and glutamic acid) were selected as the precursors for the model systems. After pasteurization and during subsequent accelerated storage (42 °C, 16 weeks) the model systems displayed a three-phase browning development. The initial browning phase was mainly the result of ascorbic acid degradation especially in the presence of amino acids and sugars. In the later phases, the contribution of reactions of sugars and amino acids to browning became apparent. The application of 1H NMR fingerprinting on a simple model system containing ascorbic acid revealed that its degradation pathway to intermediates such as xylonic acid, acetic acid and erythrulose was responsible for the major changes during storage. When this model system was complexed by inclusion of sugars and amino acids, the hydrolysis of sucrose to glucose and fructose was identified as the main reaction leading to differences in the samples throughout storage. These three sugars dominated the NMR spectra of the samples, overshadowing several important compounds for NEB such as ascorbic acid and its degradation products. Other more advanced NMR experiments such as two-dimensional NMR analyses should be applied in future research to identify unknown compounds from NEB reactions.

Species Prioritization Based on Spectral Dissimilarity: A Case Study of Polyporoid Fungal Species.

Biological species collections are critical for natural product drug discovery programs. However, prioritization of target species in massive collections remains difficult. Here, we introduce an untargeted metabolomics-based prioritization workflow that uses MS/MS molecular networking to estimate scaffold-level distribution. As a demonstration, we applied the workflow to 40 polyporoid fungal species. Nine species were prioritized as candidates based on the chemical structural and compositional similarity (CSCS) metric. Most of the selected species showed relatively higher richness and uniqueness of metabolites than those of the others. Cryptoporus volvatus, one of the prioritized species, was investigated further. The chemical profiles of the extracts of C. volvatus culture and fruiting bodies were compared, and it was shown that derivative-level diversity was higher in the fruiting bodies; meanwhile, scaffold-level diversity was similar. This showed that the compounds found from a cultured fungus can also be isolated in wild mushrooms. Targeted isolation of the fruiting body extract yielded three unknown (1-3) and six known (4-9) cryptoporic acid derivatives, which are drimane-type sesquiterpenes with isocitric acid moieties that have been reported in this species. Cryptoporic acid T (1) is a trimeric cryptoporic acid reported for the first time. Compounds 2 and 5 exhibited cytotoxicity against HCT-116 cell lines with IC50 values of 4.3 and 3.6 µM, respectively.

Updated Reaction Pathway for Dichloramine Decomposition: Formation of Reactive Nitrogen Species and N-Nitrosodimethylamine.

The N-nitrosodimethylamine (NDMA) formation pathway in chloraminated drinking water remains unresolved. In pH 7-10 waters amended with 10 µM total dimethylamine and 800 µeq Cl2·L-1 dichloramine (NHCl2), NDMA, nitrous oxide (N2O), dissolved oxygen (DO), NHCl2, and monochloramine (NH2Cl) were kinetically quantified. NHCl2, N2O, and DO profiles indicated that reactive nitrogen species (RNS) formed during NHCl2 decomposition, including nitroxyl/nitroxyl anion (HNO/NO-) and peroxynitrous acid/peroxynitrite anion (ONOOH/ONOO-). Experiments with uric acid (a ONOOH/ONOO- scavenger) implicated ONOOH/ONOO- as a central node for NDMA formation, which were further supported by the concomitant N-nitrodimethylamine formation. A kinetic model accurately simulated NHCl2, NH2Cl, NDMA, and DO concentrations and included (1) the unified model of chloramine chemistry revised with HNO as a direct product of NHCl2 hydrolysis; (2) HNO/NO- then reacting with (i) HNO to form N2O, (ii) DO to form ONOOH/ONOO-, or (iii) NHCl2 or NH2Cl to form nitrogen gas; and (3) NDMA formation via ONOOH/ONOO- or their decomposition products reacting with (i) dimethylamine (DMA) and/or (ii) chlorinated unsymmetrical dimethylhydrazine (UDMH-Cl), the product of NHCl2 and DMA. Overall, updated NHCl2 decomposition pathways are proposed, yielding (1) RNS via NHCl2→HNO/NO-→O2ONOOH/ONOO- and (2) NDMA via ONOOH/ONOO-→UDMH-ClorDMANDMA.

Influence of pH and Composition on Nonenzymatic Browning of Shelf-Stable Orange Juice during Storage.

Nonenzymatic browning during storage of pasteurized shelf-stable orange juice causes a major color deterioration, which negatively affects consumer acceptance of the juice. This study, for the first time, investigated on a kinetic basis the effect of pH and suspected nonenzymatic browning reaction precursors such as ascorbic acid, fructose, and arginine on nonenzymatic browning during accelerated storage (42 °C) using an orange-juice-based model system. The results showed that lowering the pH of the model juice system from 3.8 to 1.5 significantly increased the rate of ascorbic acid degradation, the rate changes (increases and decreases) in different sugars, and the rates of furfural and 5-hydroxymethylfurfural formation. These changes coincided with a higher browning intensity, which became more pronounced toward the end of storage of the juice model system. Similarly, adding more ascorbic acid and fructose largely increased the formation of furfural and 5-hydroxymethylfurfural, respectively, and resulted in a higher browning intensity. In conclusion, lowering the pH of the orange juice or addition of ascorbic acid or fructose will enhance its browning during prolonged storage.

Changes in the Soluble and Insoluble Compounds of Shelf-Stable Orange Juice in Relation to Non-Enzymatic Browning during Storage.

For the first time in literature, this study revealed the participation of polymeric components of orange juice cloud and pulp (such as proteins, arabinogalactan proteins, or protein-pectin complexes) during nonenzymatic browning. In a quest to better understand the nonenzymatic browning of shelf-stable orange juice during storage, the juice was fractionated into different fractions depending on the solubility in water/ethanol and the obtained fractions were characterized. The results showed that brown compounds that were formed during storage of orange juice were distributed over water insoluble (pulp), ethanol insoluble (cloud), and ethanol soluble (serum) fractions. In the ethanol insoluble fraction, the brown compounds are hypothesized to be associated with proteins, arabinogalactan proteins, and/or protein-pectin complexes of this fraction without significantly changing their molecular weight distributions, monosaccharide compositions, and protein contents. The changes in the ethanol soluble fraction including ascorbic acid degradation, acid-catalyzed hydrolysis of sucrose, and formation of furfural and 5-hydroxymethylfurfural were highly correlated to the browning development of the juice during storage.

Long-term Outcomes of Stereotactic Body Radiotherapy for Low-Risk and Intermediate-Risk Prostate Cancer.

Importance: Stereotactic body radiotherapy harnesses improvements in technology to allow the completion of a course of external beam radiotherapy treatment for prostate cancer in the span of 4 to 5 treatment sessions. Although mounting short-term data support this approach, long-term outcomes have been sparsely reported. Objective: To assess long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. Design, Setting, and Participants: This cohort study analyzed individual patient data from 2142 men enrolled in 10 single-institution phase 2 trials and 2 multi-institutional phase 2 trials of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer between January 1, 2000, and December 31, 2012. Statistical analysis was performed based on follow-up from January 1, 2013, to May 1, 2018. Main Outcomes and Measures: The cumulative incidence of biochemical recurrence was estimated using a competing risk framework. Physician-scored genitourinary and gastrointestinal toxic event outcomes were defined per each individual study, generally by Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events scoring systems. After central review, cumulative incidences of late grade 3 or higher toxic events were estimated using a Kaplan-Meier method. Results: A total of 2142 men (mean [SD] age, 67.9 [9.5] years) were eligible for analysis, of whom 1185 (55.3%) had low-risk disease, 692 (32.3%) had favorable intermediate-risk disease, and 265 (12.4%) had unfavorable intermediate-risk disease. The median follow-up period was 6.9 years (interquartile range, 4.9-8.1 years). Seven-year cumulative rates of biochemical recurrence were 4.5% (95% CI, 3.2%-5.8%) for low-risk disease, 8.6% (95% CI, 6.2%-11.0%) for favorable intermediate-risk disease, 14.9% (95% CI, 9.5%-20.2%) for unfavorable intermediate-risk disease, and 10.2% (95% CI, 8.0%-12.5%) for all intermediate-risk disease. The crude incidence of acute grade 3 or higher genitourinary toxic events was 0.60% (n = 13) and of gastrointestinal toxic events was 0.09% (n = 2), and the 7-year cumulative incidence of late grade 3 or higher genitourinary toxic events was 2.4% (95% CI, 1.8%-3.2%) and of late grade 3 or higher gastrointestinal toxic events was 0.4% (95% CI, 0.2%-0.8%). Conclusions and Relevance: In this study, stereotactic body radiotherapy for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control. These data suggest that stereotactic body radiotherapy is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer.

The use of natural media amendments to produce kale enhanced with functional lipids in controlled environment production system.

Diets high in vegetable consumption is highly correlated with reduced risk of developing common lifestyle related diseases. We investigated the effects of three natural growth media amendments [potassium humate, dry vermicast, volcanic minerals or Promix alone (Control)] in enhancing the accumulation of functional lipids in greenhouse grown kale. Functional lipids (n9, n6, n3 fatty acids, diglycerides, galactolipids and phytosterols) were assessed using either gas chromatography/mass spectrometry (GC/MS) or ultra-high performance liquid chromatography-high resolution tandem mass spectrometry (UHPLC-HRMS/MS). The results showed volcanic minerals and dry vermicast were the most successful in enhancing the accumulation of functional lipids in kale. For example, dry vermicast enhanced the accumulation of total C18:1n9 and C16:3n3 fatty acids, while total C18:2n6 fatty acid accumulation was enhanced by volcanic minerals. In conclusion, natural growing medium amendments are remarkably effective in modulating the accumulation of functional lipids in kale grown under controlled-environment conditions. This could be a useful strategy for functional foods production in control environment production systems. Increase access to kale with enhanced functional lipids could aid in increase consumption of these health promotive compounds in the diet with potential implications in population health.

Non-alcoholic steatofibrosis (NASF) can independently predict mortality in patients with non-alcoholic fatty liver disease (NAFLD).

BACKGROUND: Hepatic fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) independently predicts mortality. Given liver biopsy's invasive nature, non-invasive method to assess hepatic steatosis and fibrosis provides NAFLD risk stratification algorithm in clinical practice. NAFLD fibrosis score (NFS) is simple and non-invasive predictive model recommended by American Association for the Study of Liver Disease (AASLD) Guideline to identify patients with NAFLD with fibrosis risk. The aim of this study is to assess long-term outcomes of subjects with significant non-alcoholic steatofibrosis (NASF) as established by ultrasound (US) and NFS. METHODS: Used National Health and Nutrition Examination Survey (NHANES III) with National Death Index-linked Mortality Files. NAFLD diagnosis established by the presence of moderate to severe hepatic steatosis on US without other causes of chronic liver disease (alcohol consumption <20 gr/day, hepatitis B surface-antigen negative, anti-hepatitis C virus antibody negative, transferrin saturation <50%). Significant hepatic fibrosis was estimated by high NFS (>0.676) and calculated with previously published formula. Subjects with NAFLD and high NFS have significant NASF. RESULTS: NHANES III included 20 050 adult participants. 2515 participants complete data and NAFLD with 5.1% (n=129) meeting criteria for significant SF. Subjects with significant SF were older, had higher body mass index, waist circumference and the homeostasis model assessment (HOMA) scores and higher rates of comorbidities (diabetes, congestive heart failure (CHF), stroke; all p<0.001). After median of 207 months of follow-up, overall mortality in NAFLD cohort was 30.0% (n=754). Crude mortality higher in subjects with significant SF (67.4% vs 28.0%, p<0.001). In multivariate survival analysis, predictors of overall mortality included significant SF (adjusted HR (aHR): 1.37; 95% CI 1.07 to 1.76, p=0.01), older age (aHR:1.08; 95% CI 1.07 to 1.09 per year), male gender (aHR:1.44; 95% CI 1.24 to 1.67), black race (aHR:1.24; 95% CI 1.04 to 1.48)), history of hypertension (aHR:1.40; 95% CI 1.20 to 1.64), diabetes (aHR:1.69; 95% CI 1.43 to 2.00), CHF (aHR:1.77; 95% CI 1.38 to 2.261), stroke (aHR:1.84; 95% CI 1.38 to 2.48) and smoking (aHR:1.74; 95% CI 1.47 to 2.07) (all p<0.02). Sensitivity analysis showed that the best association of SF with mortality is higher at NFS threshold of 0.80 (aHR:1.41; 95% CI 1.09 to 1.83, p=0.01). CONCLUSIONS: Significant NASF determined non-invasively is an independent predictor of mortality. These data should help clinicians to easily risk-stratify patients with NAFLD for close monitoring and treatment considerations in clinical trial setting.