Percutaneous cryoablation for desmoid fibromatosis: initial experience at a UK centre.

AIM: To report the first UK experience of cryoablation in desmoid fibromatosis (DF) with particular focus on technique, safety, and efficacy. MATERIALS AND METHODS: Patients were selected at multidisciplinary tumour board meetings at a specialist cancer hospital. Radiation dose, procedure duration, and number of cryoprobes were compared for small versus large tumours (>10 cm long axis). Response at magnetic resonance imaging (MRI) was evaluated using different criteria, and percentage agreement with clinical response as assessed in oncology clinic calculated. RESULTS: Thirteen procedures were performed in 10 patients (eight women, median age 51 years, IQR 42-69 years) between February 2019 and August 2021. Procedures for large tumours had higher radiation dose (2,012 ± 1,012 versus 1,076 ± 519 mGy·cm, p=0.048) used more cryoprobes (13 ± 7 versus 4 ± 2, p=0.009), and were more likely to have residual unablated tumour (38 ± 37% versus 7.5 ± 10%, p=0.045). Adverse events were minor apart from one transient radial nerve palsy. Eight of 10 patients had symptomatic benefit at clinical follow-up (median 353 days, IQR 86-796 days), and three started systemic therapy mean 393 days later. All patients who had complete ablation demonstrated symptomatic response, with no instances of repeat treatment, recurrence, or need for systemic therapy during the study period. All progression occurred outside ablation zones. CONCLUSION: Cryoablation for symptomatic DF is a reproducible technique with low, transient toxicity, where one or two treatments can achieve a meaningful response. Where possible, the ablation ice ball should fully cover DF tumours.

Cerebral cortical thickness and gyrification changes in first-episode psychoses and multi-episode schizophrenia.

Cortical thickness (CT) and local gyrification index (LGI) in psychotic disorders may show modifications that relate to clinical course. This observational study aimed to analyse such variables in patients with schizophrenia, compared to healthy controls (HCs). We compared CT and LGI of 18 patients with first-episode psychosis with that of 21 with multi-episode schizophrenia and 16 HCs. CT corrected for false-positive cases (Family-Wise Error Rate) showed a reduction in the multi-episode group compared to HCs in left temporal and parietal, and right temporal, parietal, occipital, and hippocampal cortices. Family-wise corrected LGI was increased in the left inferior and middle frontal cortices, and in the right fusiform gyrus, cingulate, lingual, and parahippocampal gyri in first onset patients compared to HCs. Increased LGI was absent from later stages of psychosis, suggesting that specific CT and LGI alterations may underlie different stages of illness.

Oral dehydroepiandrosterone restores ß-endorphin response to OGTT in early and late postmenopause.

ß-endorphin is a neuropeptide involved in several brain functions: its plasma levels are higher in obese women and its release increases after oral glucose tolerance test (OGTT) in normal or obese women. The study included 46 healthy women and evaluated the effect of oral dehydroepiandrosterone [DHEA] (50 mg/day) in early postmenopausal women (50-55 years) both of normal weight (group A, n = 12, BMI = 22.1 ± 0.5) and overweight (group B, n = 12, BMI = 28.2 ± 0.5), and late postmenopausal women (60-65 years) both normal weight (group C, n = 11, BMI = 22.5 ± 0.6) and overweight (group D, n = 11, BMI = 27.9 ± 0.4) undergone OGTT, in order to investigate if DHEA could restore/modify the control of insulin and glucose secretion and ß-endorphin release in response to glucose load. The area under the curve (AUC) of OGTT evaluated plasma levels of different molecules. DHEA, DHEAS, and ß-endorphin plasma levels were lower in baseline conditions in older women than younger women. Considering the AUC of ß-endorphin response to OGTT, all groups showed a progressive significant increase after 3 and also after 6 months of treatment in comparison to baseline and 3 months of treatment.

Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients.

PURPOSE: To evaluate the efficacy of alpha-lipoic acid (ALA) administration on hormonal and metabolic parameters of obese PCOS patients. METHODS: A group of 32 obese PCOS patients were selected after informed consent. 20 patients referred to have first grade relatives with diabetes type I or II. Hormonal and metabolic parameters as well as OGTT were evaluated before and after 12 weeks of ALA integrative administration (400 mg per os every day). RESULTS: ALA administration significantly decreased insulin, glucose, BMI and HOMA index. Hyperinsulinemia and insulin response to OGTT decreased both as maximal response (Δmax) and as AUC. PCOS with diabetes relatives showed the decrease also of triglyceride and GOT. Interestingly in all PCOS no changes occurred on all hormonal parameters involved in reproduction such as LH, FSH, and androstenedione. CONCLUSIONS: ALA integrative administration at a low dosage as 400 mg daily improved the metabolic impairment of all PCOS patients especially in those PCOS with familiar diabetes who have a higher grade of risk of NAFLD and predisposition to diabetes.

Effects of the mu-opioid receptor antagonist GSK1521498 on hedonic and consummatory eating behaviour: a proof of mechanism study in binge-eating obese subjects.

The opioid system is implicated in the hedonic and motivational processing of food, and in binge eating, a behaviour strongly linked to obesity. The aim of this study was to evaluate the effects of 4 weeks of treatment with the mu-opioid receptor antagonist GSK1521498 on eating behaviour in binge-eating obese subjects. Adults with body mass index ≥ 30 kg m(-2) and binge eating scale scores ≥ 19 received 1-week single-blind placebo run-in, and were then randomized to 28 days with either 2 mg day(-1) GSK1521498, 5 mg day(-1) GSK1521498 or placebo (N=21 per arm) in a double-blind parallel group design. The outcome measures were body weight, fat mass, hedonic and consummatory eating behaviour during inpatient food challenges, safety and pharmacokinetics. The primary analysis was the comparison of change scores in the higher-dose treatment group versus placebo using analysis of covariance at each relevant time point. GSK1521498 (2 mg and 5 mg) was not different from placebo in its effects on weight, fat mass and binge eating scores. However, compared with placebo, GSK1521498 5 mg day(-1) caused a significant reduction in hedonic responses to sweetened dairy products and reduced calorific intake, particularly of high-fat foods during ad libitum buffet meals, with some of these effects correlating with systemic exposure of GSK1521498. There were no significant effects of GSK1521498 2 mg day(-1) on eating behaviour, indicating dose dependency of pharmacodynamics. GSK1521498 was generally well tolerated and no previously unidentified safety signals were detected. The potential for these findings to translate into clinically significant effects in the context of binge eating and weight regain prevention requires further investigation.

Clinical and genetic features of dominant Essential Tremor in Tuscany, Italy: FUS, CAMTA1, ATXN1 and beyond.

OBJECTIVE: Essential Tremor (ET) is one of the most common neurological disorders. In most instances ET is inherited as an autosomal dominant trait with age-related penetrance (virtually complete in advanced age); however, ET genetics remains elusive. The current study aims to identify possibly pathogenic genetic variants in a group of well-characterized ET families. METHODS: 34 individuals from 14 families with dominant ET were clinically evaluated and studied by whole exome sequencing studies (after excluding trinucleotide expansion disorders). RESULTS: Most patients had pure ET. In 4 families, exome studies could identify a genetic variant potentially able to significantly alter the protein structure (CADD >20, REVEL score > 0.25), shared by all the affected individuals (in CAMTA1, FUS, MYH14, SGCE genes). In another family there were two variants in dominant genes (PCDH9 and SQSTM1). Moreover, an interrupted "intermediate" trinucleotide expansion in ATXN1 ("SCA1") was identified in a further family with pure ET. CONCLUSION: Combining our observations together with earlier reports, we can conclude that ET genes confirmed in at least two families to date include CAMTA1 and FUS (reported here), as well as CACNA1G, NOTCH2NLC and TENM4. Most cases of familial ET, inherited with an autosomal dominant inheritance, may result from "mild" variants of many different genes that, when affected by more harmful genetic variants, lead to more severe neurological syndromes (still autosomal dominant). Thus, ET phenotype may be the "mild", incomplete manifestation of many other dominant neurogenetic diseases. These findings further support evidence of genetic heterogeneity for such disease(s). Author's keywords: cerebellar ataxias, movement disorders, neurogenetics, rare neurological disorders, tremor.

S-p-bromobenzyl-glutathione cyclopentyl diester (BBGC) as novel therapeutic strategy to enhance trabectedin anti-tumor effect in soft tissue sarcoma preclinical models.

Trabectedin, approved for the treatment of soft tissue sarcoma (STS), interferes with cell division and genetic transcription processes. Due to its strong anti-tumor activity in only certain histotypes, several studies on trabectedin combinations are currently ongoing to improve its efficacy. In this study, we aimed to investigate novel potential therapeutic strategies to enhance the anti-tumor effect of trabectedin using integrated in silico, in vitro, and in vivo approaches. For in silico analysis, we screened two public datasets, GSEA M5190 and TCGA SARC. Fibrosarcoma, leiomyosarcoma, dedifferentiated, and myxoid liposarcoma cell lines were used for in vitro studies. For in vivo experiments, fibrosarcoma orthotopic murine model was developed. In silico analysis identified Glo1 as the only druggable target upregulated after trabectedin treatment and correlated with poor prognosis. The specific Glo1 inhibitor, S-p-bromobenzylglutathione cyclopentyl diester (BBGC), increased trabectedin cytotoxicity in STS cells, and restored drug sensitivity in myxoid liposarcoma cells resistant to trabectedin. Moreover, the combined treatment with BBGC and trabectedin had a synergistic antitumor effect in vivo without any additional toxicity to mice. Based on these results, we believe that BBGC warrants further investigation to evaluate its potential clinical use in combination with trabectedin.

Low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma, outcome of advanced disease: retrospective study from the Ultra-Rare Sarcoma Working Group.

BACKGROUND: To present findings from a retrospective study conducted by the Ultra-Rare Sarcoma Working Group on metastatic low-grade fibromyxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), and hybrid (H)-LGFMS/SEF across 28 global centres. METHODS: Patients treated at participating institutions from January 2000 to September 2022 were retrospectively selected. Diagnosis was confirmed by expert pathologists. Primary endpoint was progression-free survival (PFS-1) from metastasis detection to first progression or death. PFS-2 was calculated from therapy initiation. RESULTS: A total of 101 patients were identified (32 LGFMS, 50 SEF, 19 H-LGFMS/SEF). Median (m) follow-up was 62.1 months. mPFS-1 was 28.7, 11.8, and 20.3 months for LGFMS, SEF, and H-LGFMS/SEF, respectively. mOS was 145.8, 41.9, and 113.5 months, respectively. Treatments included anthracycline-based chemotherapy, gemcitabine-based chemotherapy (G), pazopanib, trabectedin, others. mPFS-2 was: 20.1, 5.5, and 3.5 months in H-LGFMS/SEF, SEF, and LGFMS, respectively, with anthracyclines; 19.5, 7.7, and 6.9 months in LGFMS, SEF, and H-LGFMS/SEF, respectively, with pazopanib; 12.0, 9.7, and 3.1 months in H-LGFMS/SEF, LGFMS, and SEF, respectively. Occasional responses occurred with ifosfamide/oral cyclophosphamide, and prolonged stable disease with immune checkpoint inhibitors. CONCLUSIONS: In this series, the largest available, metastatic LGFMS, SEF, and H-LGFMS/SEF showed different courses. Systemic agents have modest efficacy, informing future trials of novel agents for these tumours.

GSK256073, a selective agonist of G-protein coupled receptor 109A (GPR109A) reduces serum glucose in subjects with type 2 diabetes mellitus.

AIMS: This clinical trial assessed whether a potent, selective GPR109A agonist, GSK256073, could, through inhibition of lipolysis, acutely improve glucose homeostasis in subjects with type 2 diabetes mellitus. METHODS: Thirty-nine diabetic subjects were enrolled in the randomized, single-blind, placebo-controlled, three-period crossover trial. Each subject received placebo and two of four regimens of GSK256073 for 2 days. GSK256073 was dosed 5 mg every 12 h before breakfast and supper (BID), 10 mg every 24 h before breakfast (QD), 25 mg BID and 50 mg QD. RESULTS: The change from baseline weighted mean glucose concentration for an interval from 24 to 48 h after the initial drug dose was significantly reduced for all GSK256073 regimens, reaching a maximum of -0.87 mmol/l (-1.20, -0.52) with the 25 mg BID dose. Sustained suppression of non-esterified fatty acid (NEFA) and glycerol concentrations was observed with all GSK256073 doses throughout the 48-h dosing period. Serum insulin and C-peptide concentrations fell in concert with glucose concentrations and calculated HOMA-IR scores decreased 27-47%, consistent with insulin sensitization. No marked differences were evident between either 10 and 50 mg total daily doses or QD versus BID dosing. CONCLUSIONS: Administration of a GPR109A agonist for 2 days significantly decreased serum NEFA and glucose concentrations in diabetic subjects. Glucose improvements were associated with decreased insulin concentrations and measures of enhanced insulin sensitivity. Improved glucose control occurred with GSK256073 doses that were generally safe and not associated with events of flushing or gastrointestinal disturbances.

Validity and metric of MiniMental Parkinson and MiniMental State Examination in Parkinson's disease.

The MiniMental Parkinson (MMP) has been derived from the MiniMental State Examination (MMSE) for the screening of cognitive impairment in Parkinson's disease by adding subtests that were focused on executive and visuo-spatial impairment more than on memory or language deficits. In this multicenter study, the psychometric and validity properties of the MMP have been evaluated in 69 cognitively intact and 52 cognitively impaired patients with Parkinson's disease, classified according to their performance at the Dementia Rating Scale. The MMP showed better metrics and convergent validity, and higher screening ability. However, its performance was not fully satisfying in terms of data distribution, coefficient of variation and specificity, and Receiver Operating Characteristic curves did not show clear cut superiority of either scale at their best sensitivity-specificity trade off. The MMP seems to be slightly preferable to the MMSE only at a cut off that favours sensitivity with respect to specificity, for screening purposes. The test is simple and quick, but has limitations in terms of validity.

Dirofilariosis infestation of pectoralis major muscle in Italy, a case report.

Abstract: Zoonotic dirofilariasis infestation, caused by Dirofilaria Repens, is described worldwide in different countries. A 31-years-old male patient presented thoracic muscle pain after growth of an ovoidal undefine cyst in left parasternal region. Patient reported several contacts with different species of animals for a familiar activity. In absence of blood inflammatory indices and systemic symptoms, imaging studies showed a suspected muscle cyst infection. Surgical excision was performed and microbiology confirmed parasite nature. Dirofilaria Repens, probably adult female, was identified. Treatment resulted to be definitive and any other clinical and surgical approach was needed. Healing time was uneventful and follow-up showed no further systemic relapses. The case highlights the effectiveness of surgical treatment in this subcutaneous infestation for an increasing number of human cases reported in endemic areas such as Central Italy.

Role of the association of high-risk HPV identified by real-time PCR in cervical preneoplastic lesions.

OBJECTIVE: To evaluate the effects of infection in multiple types of high-risk human papilloma virus (HPV) in cervical preneoplastic lesions in patients undergoing colposcopy following a diagnosis of atypical squamous cells of unknown significance (ASCUS) and low-grade squamous intraepithelial (LSIL) cytology. MATERIALS AND METHODS: Between 2009 and 2010, 2,500 patients were recruited with a mean age of 35 +/- 5 years. Screening for cervical cancer was performed and in case of ASCUS and LSIL the patients underwent colposcopy. The tests for the detection and typing of viral DNA (HPV - DNA test) were performed on cervical swab with real-time PCR amplification. RESULTS: The prevalence of infection was 70% (1579/2256) in the patients recruited. In relation to the degree of preneoplastic lesions some high-risk HPV viral genotypes were identified: HPV 16 (319/1466), HPV 18 (164/1466), HPV 45 (76/1466), HPV 31 (215/1466), HPV 52 (145/1466), HPV 58 (55/1466) HPV 56 (79/1466), HPV 51 (110/1466), HPV 6(138/1466), HPV 11 (88/1466), HPV 42 (34/1466), HPV 53 (43/1466). In case of high-grade lesions of CIN (CIN2 and CIN3) a greater HPV co-infection was detected and in particular the association from 16 to 18 (70%), 16-33 (18%) and 16 to 52 (12%). CONCLUSIONS: Infection caused by the simultaneous presence of multiple HPV genotypes appears to be associated with a significantly increased risk of high-grade lesions of CIN or invasive cancer than the presence of single viral infections. The infection with multiple HPV types is a significant risk factor for high-grade lesions of CIN in women undergoing colposcopy for ASCUS cytology/LSIL. The use of real-time PCR has shown the ability not only to identify the different types of HPV, but also to monitor quantitatively the same over time, and during the study phase, to evaluate the sensitivity and specificity of the method in comparison with other techniques.

The role of hypertension, body mass index, and serum leptin levels in patients with endometrial hyperplasia during premenopausal period.

OBJECTIVES: to investigate whether body mass index (BMI), hypertension (HTN), diabetes, age, and physical activity can be considered risk factors for endometrial simple hyperplasia in premenopausal women. Furthermore this study was undertaken to determine whether serum concentration of leptin in patients with BMI>or= 30 kg / m2 with endometrial hyperplasia deviate from values in patients with normal endometrium. MATERIALS AND METHODS: The authors enrolled 167 hyperplasia cases and 282 controls. Demographic characteristics and data on age, diabetes, hypertension, BMI, physical activity, and anthropometric parameters were collected. Leptin concentration in serum was measured with immunoenzymatic test kit from IBL. Univariable and multivariable analysis were performed to verify the association among age, HTN, BMI, physical activity, diabetes, and the presence of uterine hyperplasia. Furthermore the authors evaluated the correlation between BMI and leptin level (with Pearson's linear correlation) in women with simple hyperplasia and in controls. RESULTS: The prevalence of hyperplasia found was 34.4%. The following factors were independently associated with increased risk of endometrial hyperplasia: HTN (odds ratio 3.19, 95% confidence interval 1.20-8.48, p<0.020) and BMI>or=30 Kg/m2 (odds ratio 6.43, 95% confidence interval 3.92-10.53, p<0.000). Mean leptin concentration in serum was higher in patients who had endometrial hyperplasia than in controls (p<0.005) and the leptin levels depended on BMI. CONCLUSIONS: The following are risk factors for endometrial hyperplasia in premenopausal women: BMI>or=30 kg/m2 and HTN (blood pressure>or=130/85 or in therapy). Leptin appears to participate in proliferative processes of the endometrium, depending on BMI. Current guidelines may need to be reconsidered.

DTI parameters in neonates with hypoxic-ischemic encephalopathy after total body hypothermia.

BACKGROUND AND PURPOSE: MR imaging provides means for discriminating different patterns of Hypoxic-ischemic encephalopathy (HIE) and may distinguish most severe cases from less severe but is unable to predict long-term outcome. Diffusion tensor imaging (DTI) offers information for a more complete characterization of HIE. The purpose of this study is to compare the modifications of DTI parameters in newborns one week and six months following total-body cooling to healthy controls. METHODS: Forty-seven cooled newborns were studied with MRI, 20 underwent follow-up at 6 months. 12 healthy newborns and nine children at 6 months were enrolled as control groups (HC). Inferior Longitudinal Fasciculus (ILF), Corpus Callosum Fasciculus (CCF), Corticospinal Tract (CST), Optical Tract (OT), Optic Radiation (OR) were generated in all subjects. DTI parameters were evaluated in basal ganglia (BG), thalamus (TH) and tracks. Statistical analysis was performed with MANOVA. RESULTS: In newborns HIE versus HC, there were significantly lower fractional anisotropy (FA) on OR and CST and higher axial diffusivity (AD), apparent diffusion coefficient (ADC) and radial diffusivity (RD) values on CST, BG and TH in HIE-N. At 6 months there were no significant grouping effects. The analysis showed a significant increase of FA, decrease of ADC, AD, RD after 6 months for HIE and HC. CONCLUSIONS: We observed modifications of parameter values in HIE newborns vs HC; however normalization of values at 6 months suggests that changes of parameters cannot be considered early biomarkers for evaluation of therapeutic hypothermia in newborns with moderate HIE and normal conventional MRI.

Early magnesium modifications as a surrogate marker of efficacy of cetuximab-based anticancer treatment in KRAS wild-type advanced colorectal cancer patients.

BACKGROUND: KRAS wild-type mutational status is necessary but not sufficient to get benefit from epidermal growth factor receptor inhibition. Predictive markers are currently being evaluated. In this study, we investigated early hypomagnesemia as a predictor of efficacy and outcome in terms of time to progression (TtP) and overall survival (OS) in a cohort of patients affected by advanced colorectal adenocarcinoma KRAS wild-type cetuximab-treated. PATIENTS AND METHODS: One hundred and forty-three patients affected by stage IV colorectal adenocarcinoma KRAS wild type receiving cetuximab + irinotecan (CTX+IRI) as third-line anticancer treatment and resistant to oxaliplatin- and irinotecan-based chemotherapy were retrospectively included. Magnesium plasma levels were measured before the first day and 7, 14, 21 and 28 days after CTX+IRI infusion. RESULTS: The median magnesium basal value showed a statistically significant decrease after the start of CTX+IRI treatment (at 28 days, P < 0.0001). Patients with an early decrease of magnesium levels >50% compared with the basal level had a higher tumor response rate (55.8% versus 16.7%, P < 0.0001), a longer TtP (6.3 versus 3.6, P < 0.0001) and a longer median OS (11.0 versus 8.1, P = 0.002). CONCLUSIONS: We have shown that early hypomagnesemia could be a predictor of efficacy and outcome in those patients. Magnesium circulating level is an easy and inexpensive biomarker to routinely be detected in patients treated with cetuximab.

Clinical prognostic factors in advanced epithelioid haemangioendothelioma: a retrospective case series analysis within the Italian Rare Cancers Network.

BACKGROUND: This multicentric, retrospective study conducted within the Italian Rare Cancer Network describes clinical features and explores their possible prognostic relevance in patients with advanced epithelioid haemangioendothelioma (EHE) started on surveillance. PATIENTS AND METHODS: We collected data on adult patients with molecularly confirmed, advanced EHE consecutively referred at five sarcoma reference centres between January 2010 and June 2018, with no evidence of progressive disease (PD) and started on surveillance. Overall survival (OS) and progression-free survival (PFS) univariable and multivariable Cox analyses were performed. In the latter, due to the low number of cases and events, penalized likelihood was applied, and variable selection was performed using a random forest model. RESULTS: Sixty-seven patients were included. With a median follow-up of 50.2 months, 51 (76%) patients developed PD and 16 (24%) remained stable. PD at treatment start did not meet RECIST version 1.1 in 15/51 (29%) patients. The 3-year PFS and OS were 25.4% and 71.1%, respectively, in the whole population. Tumour-related pain (TRP) was the most common baseline symptom (32.8%), followed by temperature (20.9%), fatigue (17.9%), and weight loss (16.4%). Baseline TRP (P = 0.0002), development of TRP during follow-up (P = 0.005), baseline temperature (P = 0.002), and development of fatigue during follow-up (P = 0.007) were associated with a significantly worst PFS. An association between baseline TRP (P < 0.0001), development of TRP during follow-up (P = 0.0009), evidence of baseline serosal effusion (P = 0.121), and OS was recorded. CONCLUSION: Because of the poor outcome observed in EHE patients presenting with serosal effusion, TRP, temperature, or serosal effusion, upfront treatment in this subgroup could be considered.

Potential prebiotic activity of oligosaccharides obtained by enzymatic conversion of durum wheat insoluble dietary fibre into soluble dietary fibre.

BACKGROUND AND AIMS: Epidemiological evidence indicates that cereal dietary fibre (DF) may have several cardiovascular health benefits. The underlying mechanisms have not yet been elucidated. Here, the potential nutritional effects of physico-chemical properties modifications of durum wheat dietary fibre (DWF) induced by enzyme treatment have been investigated. METHODS AND RESULTS: The conversion of the highly polymerised insoluble dietary fibre into soluble feruloyl oligosaccharides of DWF was achieved by a tailored enzymatic treatment. The in vitro fermentation and release of ferulic acid by intestinal microbiota from DWF before and after the enzymatic treatment were assessed using a gut model validated to mimic the human colonic microbial environment. Results demonstrated that, compared to DWF, the enzyme-treated DWF (ET-DWF) stimulated the growth of bifidobacteria and lactobacilli. Concurrently, the release of free ferulic acid by ET-DWF was almost three times higher respect to the control. No effect on the formation of short chain fatty acids was observed. CONCLUSIONS: The conversion of insoluble dietary fibre from cereals into soluble dietary fibre generated a gut microbial fermentation that supported bifidobacteria and lactobacilli. The concurrent increase in free ferulic acid from the enzyme-treated DWF might result in a higher plasma ferulic acid concentration which could be one of the reasons for the health benefits reported for dietary fibre in cardiovascular diseases.

Role of solvent, pH, and molecular size in excited-state deactivation of key eumelanin building blocks: implications for melanin pigment photostability.

Ultrafast time-resolved fluorescence spectroscopy has been used to investigate the excited-state dynamics of the basic eumelanin building block 5,6-dihydroxyindole-2-carboxylic acid (DHICA), its acetylated, methylated, and carboxylic ester derivatives, and two oligomers, a dimer and a trimer in the O-acetylated forms. The results show that (1) excited-state decays are faster for the trimer relative to the monomer; (2) for parent DHICA, excited-state lifetimes are much shorter in aqueous acidic medium (380 ps) as compared to organic solvent (acetonitrile, 2.6 ns); and (3) variation of fluorescence spectra and excited-state dynamics can be understood as a result of excited-state intramolecular proton transfer (ESIPT). The dependence on the DHICA oligomer size of the excited-state deactivation and its ESIPT mechanism provides important insight into the photostability and the photoprotective function of eumelanin. Mechanistic analogies with the corresponding processes in DNA and other biomolecules are recognized.