Association between bilirubin and biomarkers of metabolic health and oxidative stress in the MARK-AGE cohort.

Recent studies have shown that elevated concentrations of unconjugated bilirubin (UCB) may be a protective host factor against the development of noncommunicable diseases (NCDs), whereas low levels of UCB are associated with the opposite effect. The results of this European study, in which 2,489 samples were tested for their UCB concentration using high-performance liquid chromatography (HPLC) and additional data from the MARK-AGE database were used for analysis, provide further evidence that elevated UCB concentrations are linked to a lower risk of developing NCDs and may act as a predictive marker of biological aging as individuals with elevated UCB concentrations showed favorable outcomes in metabolic health and oxidative-stress-related biomarkers. These findings underline the significance of studying individuals with moderate hyperbilirubinemia and investigate UCB routinely, also in the setting of aging, since this condition affects millions of people worldwide but has been underrepresented in clinical research and practice until now.

External Support of Autologous Internal Jugular Vein Grafts with FRAME Mesh in a Porcine Carotid Artery Model.

BACKGROUND: Autologous vein grafts are widely used for bypass procedures in cardiovascular surgery. However, these grafts are susceptible to failure due to vein graft disease. Our study aimed to evaluate the impact of the latest-generation FRAME external support on vein graft remodeling in a preclinical model. METHODS: We performed autologous internal jugular vein interposition grafting in porcine carotid arteries for one month. Four grafts were supported with a FRAME mesh, while seven unsupported grafts served as controls. The conduits were examined through flowmetry, angiography, macroscopy, and microscopy. RESULTS: The one-month patency rate of FRAME-supported grafts was 100% (4/4), whereas that of unsupported controls was 43% (3/7, Log-rank p = 0.071). On explant angiography, FRAME grafts exhibited significantly more areas with no or mild stenosis (9/12) compared to control grafts (3/21, p = 0.0009). Blood flow at explantation was higher in the FRAME grafts (145 ± 51 mL/min) than in the controls (46 ± 85 mL/min, p = 0.066). Area and thickness of neo-intimal hyperplasia (NIH) at proximal anastomoses were similar for the FRAME and the control groups: 5.79 ± 1.38 versus 6.94 ± 1.10 mm2, respectively (p = 0.558) and 480 ± 95 vs. 587 ± 52 µm2/µm, respectively (p = 0.401). However, in the midgraft portions, the NIH area and thickness were significantly lower in the FRAME group than in the control group: 3.73 ± 0.64 vs. 6.27 ± 0.64 mm2, respectively (p = 0.022) and 258 ± 49 vs. 518 ± 36 µm2/µm, respectively (p = 0.0002). CONCLUSIONS: In our porcine model, the external mesh FRAME improved the patency of vein-to-carotid artery grafts and protected them from stenosis, particularly in the mid regions. The midgraft neo-intimal hyperplasia was two-fold thinner in the meshed grafts than in the controls.

Fabrication of phenolic loaded spray-dried nanoliposomes stabilized by chitosan and whey protein: Digestive stability, transepithelial transport and bioactivity retention of phenolics.

Low bioavailability of phenolic compounds (phenolics) results in low in vivo bioactivity, thus their co-encapsulation could enhance potential health benefits. In this study, reconstitutable nanoliposomes loaded with phenolics varying in solubility were fabricated using spray drying after stabilized by chitosan (CH) or whey protein (WP). The physicochemical properties, biocompatibility, digestive fate, and bioactivity retention of phenolics in different forms were investigated. The surface charge of nanoliposomes (NL) shifted from -18.7 mV to positive due to conjugation with cationic CH (53.1 mV) and WP (14 mV) after spray drying while it was -26.6 mV for only spray-dried phenolics (SDP). Encapsulation efficiency of the tested phenolics ranged between 64.7 % and 95.1 %. Simulated gastrointestinal digestion/Caco-2 cell model was used to estimate the digestive fate of the phenolics yielding up to 3-fold higher bioaccessibility for encapsulated phenolics compared to their native form, combined or individually. However, the cellular uptake or transepithelial transport of phenolics did not differ significantly among formulations, except trans-resveratrol in WP-NL. On the contrary, the suppressive effect of phenolics on fatty acid induced hepatocellular lipid accumulation was strongly dependent on the encapsulation method, no activity was retained by SDP. These findings suggested that reconstitutable nanoliposomes can improve the absorption of phenolics by facilitating their bioaccessibility and thermal and/or processing stability during spray drying.

Bladder exstrophy-epispadias complex: The effect of urotherapy on incontinence.

INTRODUCTION: Achieving urinary continence is a key goal in children born with the bladder exstrophy-epispadias complex (BEEC). Unfortunately, this goal is only moderately achieved despite sometimes extensive surgical treatment. Undergoing repeated hospitalization and operations may consequently have a negative impact on quality of life. We therefore believe that other, conservative treatment options should be explored in an earlier stage of incontinence treatment in BEEC patients. As part of this, an intensive urotherapy program based on was offered to patients with persistent incontinence after reconstructive surgery for BEEC. OBJECTIVE: The aim of this study is to evaluate the benefits of intensive urotherapy on incontinence after reconstructive surgery in children with BEEC. STUDY DESIGN: A retrospective chart study was performed including all children who were enrolled in an intensive urotherapy program because of persistent incontinence after reconstructive surgery for BEEC. Urotherapy consisted of a ten-day inpatient training program based on cognitive behavioral therapy, with intensive follow-up by experienced urotherapists. Main outcome measurement was continence, expressed as the percentage of children that achieved complete continence (good result; 100% dry) or 50-99% decrease of wet days a week (improved result) after treatment. RESULTS: Data of 33 patients with a mean age of 10.6 years were analyzed. In 61% of cases (20/33) an improved or good result was reported on incontinence after urotherapy. Children with classic bladder exstrophy more often achieved a good or improved result (13/16; 81%), compared to children with epispadias (6/16; 38%). The only patient with a cloacal exstrophy completed treatment with an improved result. From the group of patients with persistent incontinence, 75% (12/16) reported that the complaints were socially acceptable at the end of follow-up. DISCUSSION: By following our intensive urotherapy program the majority of patients achieved complete continence or improved incontinence. In addition, our results show that the inpatient training program has a positive impact on acceptance in cases of persistent incontinence. The urotherapists offer individualized care and clear guidance, which we deem essential elements of successful treatment. Considering that repeated surgery may impede progress and offers no guarantee of continence, we recommend giving preference to conservative treatment options. CONCLUSION: Our results show that 37% (12/33) of patients with BEEC who were enrolled in our intensive urotherapy program because of persistent incontinence after reconstructive surgery, achieved complete continence after urotherapy and 63% (21/33) still experienced some degree of incontinence. 75% of patients who did not achieve complete continence, described the remaining incontinence as socially acceptable. These findings strongly support counselling patients with BEEC to consider conservative treatment before opting for further surgery.

Metabolism of 11'-α- and 11'-γ-Tocomonoenols in HepG2 Cells Favors the γ-Congener and Results Predominantly in Carboxymethylbutyl-Hydroxychromans.

SCOPE: Tocomonoenols (T1) are little-known vitamin E derivatives naturally occurring in foods. Limited knowledge exists regarding the cellular uptake and metabolism of α-tocomonoenol (αT1) and none about that of γ-tocomonoenol (γT1). METHODS AND RESULTS: The study investigates the cytotoxicity, uptake, and metabolism of αT1 and γT1 in HepG2 cells compared to the α- and γ-tocopherols (T) and -tocotrienols (T3). None of the studied tocochromanols are cytotoxic up to 100 µmol L-1. The uptake of the γ-congeners is significantly higher than that of the corresponding α-forms, whereas no significant differences are observed based on the degree of saturation of the sidechain. Carboxymethylbutyl-hydroxychromans (CMBHC) are the predominant short-chain metabolites of all tocochromanols and conversion is higher for γT1 than αT1 as well as for the γ-congeners of T and T3. The rate of metabolism increases with the number of double bonds in the sidechain. The rate of metabolic conversion of the T1 is more similar to tocopherols than to that of the tocotrienols. CONCLUSION: This is the first evidence that both αT1 and γT1 follow the same sidechain degradation pathway and exert similar rates of metabolism than tocopherols. Therefore, investigation into the biological activities of tocomonoenols is warranted.

Low ß-carotene bioaccessibility and bioavailability from high fat, dairy-based meal.

PURPOSE: The original aim of the study was to determine, in a double-blind 3-arm crossover human trial (n = 7), the effect of supplemental levels of iron (25 mg) and zinc (30 mg) on ß-carotene (synthetic) bioavailability (10 h postprandial). However, despite the high dose of supplemental ß-carotene (15 mg) consumed with the high fat (18 g), dairy-based breakfast test meal, there was a negligible postprandial response in plasma and triglyceride rich fraction ß-carotene concentrations. We then systematically investigated the possible reasons for this low bioavailability of ß-carotene. METHODS: We determined (1) if the supplemental ß-carotene could be micellised and absorbed by epithelial cells, using a Caco-2 cell model, (2) if the fat from the test meal was sufficiently bioavailable to facilitate ß-carotene bioavailability, (3) the extent to which the ß-carotene could have been metabolised and converted to retinoic acid/retinol and (4) the effect of the test meal matrix on the ß-carotene bioaccessibility (in vitro digestion) and Caco-2 cellular uptake. RESULTS: We found that (1) The supplemental ß-carotene could be micellised and absorbed by epithelial cells, (2) the postprandial plasma triacylglycerol response was substantial (approximately 75-100 mg dL-1 over 10 h), indicating sufficient lipid bioavailability to ensure ß-carotene absorption, (3) the high fat content of the meal (approximately 18 g) could have resulted in increased ß-carotene metabolism, (4) ß-carotene bioaccessibility from the dairy-based test meal was sixfold lower (p < 0.05) than when digested with olive oil. CONCLUSION: The low ß-carotene bioavailability is probably due to a combination of the metabolism of ß-carotene to retinol by BCMO1 and interactions of ß-carotene with the food matrix, decreasing the bioaccessibility. TRAIL REGISTRATION: The human trail was retrospectively registered (ClinicalTrail.gov ID: NCT05840848).

Potentials and limitations of a food group-based algorithm to assess dietary nutrient intake of women in rural areas in Tanzania.

The aim of this study was to evaluate the accuracy of nutrient intake assessment with the food group-based algorithm "Calculator of Inadequate Micronutrient Intake" (CIMI) in comparison to the established nutrition software NutriSurvey. Using Food Frequency Questionnaires and 24-h dietary recalls of 1010 women from two rural districts in Tanzania, 23 relevant typical Tanzanian food groups were identified and subsequently the dietary protocols assessed via CIMI algorithm were compared by bivariate correlations and Bland-Altman analysis with the results of the NutriSurvey software (reference) and were set in relation to blood biomarkers of 666 participants. CIMI and NutriSurvey calculations regarding macro- and micronutrient intakes were similar. The Bland-Altman analyses and correlation coefficients of energy (0.931), protein (0.898), iron (0.775) and zinc (0.838) confirm the agreement of both calculations. The food group based CIMI algorithm is a practical tool to identify the inadequacy of macro- and micronutrient intake at population level.

Monodopsis subterranea is a source of α-tocomonoenol, and its concentration, in contrast to α-tocopherol, is not affected by nitrogen depletion.

α-Tomonoenols (αT1) are tocochromanols structurally related to tocopherols (T) and tocotrienols (T3), the bioactive members of the vitamin E family. However, limited evidence exists regarding the sources and biosynthesis of tocomonoenols. Nitrogen depletion increases the content of α-tocopherol (αT), the main vitamin E congener, in microalgae, but little is known regarding its effect on other tocochromanols, such as tocomonoenols and tocotrienols. We therefore quantified the concentrations of T, T1, and T3, in freeze-dried biomass from nitrogen-sufficient, and nitrogen-depleted Monodopsis subterranea (Eustigmatophyceae). The identities of isomers of αT1 were confirmed by LC-MS and GC-MS. αT was the predominant tocochromanol (82% of total tocochromanols). αT1 was present in higher quantities than the sum of all T3 (6% vs. 1% of total tocochromanols). 11'-αT1 was the main αT1 isomer. Nitrogen depletion increased αT, but not αT1 or T3 in M. subterranea. In conclusion, nitrogen depletion increased the content of αT, the biologically most active form of vitamin E, in M. subterranea without affecting αT1 and T3 and could potentially be used as a strategy to enhance its nutritional value but not to increase αT1 content, indicating that αT1 accumulation is independent of that of αT in microalgae.

LRP10 and α-synuclein transmission in Lewy body diseases.

Autosomal dominant variants in LRP10 have been identified in patients with Lewy body diseases (LBDs), including Parkinson's disease (PD), Parkinson's disease-dementia (PDD), and dementia with Lewy bodies (DLB). Nevertheless, there is little mechanistic insight into the role of LRP10 in disease pathogenesis. In the brains of control individuals, LRP10 is typically expressed in non-neuronal cells like astrocytes and neurovasculature, but in idiopathic and genetic cases of PD, PDD, and DLB, it is also present in α-synuclein-positive neuronal Lewy bodies. These observations raise the questions of what leads to the accumulation of LRP10 in Lewy bodies and whether a possible interaction between LRP10 and α-synuclein plays a role in disease pathogenesis. Here, we demonstrate that wild-type LRP10 is secreted via extracellular vesicles (EVs) and can be internalised via clathrin-dependent endocytosis. Additionally, we show that LRP10 secretion is highly sensitive to autophagy inhibition, which induces the formation of atypical LRP10 vesicular structures in neurons in human-induced pluripotent stem cells (iPSC)-derived brain organoids. Furthermore, we show that LRP10 overexpression leads to a strong induction of monomeric α-synuclein secretion, together with time-dependent, stress-sensitive changes in intracellular α-synuclein levels. Interestingly, patient-derived astrocytes carrying the c.1424 + 5G > A LRP10 variant secrete aberrant high-molecular-weight species of LRP10 in EV-free media fractions. Finally, we show that this truncated patient-derived LRP10 protein species (LRP10splice) binds to wild-type LRP10, reduces LRP10 wild-type levels, and antagonises the effect of LRP10 on α-synuclein levels and distribution. Together, this work provides initial evidence for a possible functional role of LRP10 in LBDs by modulating intra- and extracellular α-synuclein levels, and pathogenic mechanisms linked to the disease-associated c.1424 + 5G > A LRP10 variant, pointing towards potentially important disease mechanisms in LBDs.

What's in a score: A longitudinal investigation of scores based on item response theory and classical test theory for the Amsterdam Instrumental Activities of Daily Living Questionnaire in cognitively normal and impaired older adults.

OBJECTIVE: We aimed to investigate whether item response theory (IRT)-based scoring allows for a more accurate, responsive, and less biased assessment of everyday functioning than traditional classical test theory (CTT)-based scoring, as measured with the Amsterdam Instrumental Activities of Daily Living Questionnaire. METHOD: In this longitudinal multicenter study including cognitively normal and impaired individuals, we examined IRT-based and CTT-based score distributions and differences between diagnostic groups using linear regressions, and investigated scale attenuation. We compared change over time between scoring methods using linear mixed models with random intercepts and slopes for time. RESULTS: Two thousand two hundred ninety-four participants were included (66.6 ± 7.7 years, 54% female): n = 2,032 (89%) with normal cognition, n = 93 (4%) with subjective cognitive decline, n = 79 (3%) with mild cognitive impairment, and n = 91 (4%) with dementia. At baseline, IRT-based and CTT-based scores were highly correlated (r = -0.92). IRT-based scores showed less scale attenuation than CTT-based scores. In a subsample of n = 1,145 (62%) who were followed for a mean of 1.3 (SD = 0.6) years, IRT-based scores declined significantly among cognitively normal individuals (unstandardized coefficient [B] = -0.15, 95% confidence interval, 95% CI [-0.28, -0.03], effect size = -0.02), whereas CTT-based scores did not (B = 0.20, 95% CI [-0.02, 0.41], effect size = 0.02). In the other diagnostic groups, effect sizes of change over time were similar. CONCLUSIONS: IRT-based scores were less affected by scale attenuation than CTT-based scores. With regard to responsiveness, IRT-based scores showed more signal than CTT-based scores in early disease stages, highlighting the IRT-based scores' superior suitability for use in preclinical populations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Acrylamide increases and furanoic compounds decrease in plant-based meat alternatives during pan-frying.

Plant-based meat alternatives are gaining popularity as protein sources. However, pan-frying may lead to the formation of potentially harmful food contaminants. We investigated the formation of acrylamide and furanoic compounds in four different plant-based meat alternatives and two meat burger patties during pan-frying at 160 and 200 °C. The highest acrylamide contents (72. ± 7.7 and 69.2 ± 9.5 µg/kg, respectively) were found in soy flour- and sunflower-protein based patties fried at 200 °C. Unprepared pea and soy protein-based burger patties contained the highest furfural amounts (2832.8 ± 576.2 and 2683.0 ± 868.5 µg/kg, respectively). Furfuryl alcohol content was highest in soy flour-based patties and increased temperature-dependently up to 1120.9 ± 383.4 µg/kg. Based on the tolerable intake calculated by the EFSA Scientific Panel on Contaminants in the Food Chain, these amounts do not pose a health risk. Nevertheless, since plant-based novel food are being increasingly consumed, further investigations into the formation of food contaminants in novel processed foods are warranted.

Dietary Intake of Fructooligosaccharides Protects against Metabolic Derangements Evoked by Chronic Exposure to Fructose or Galactose in Rats.

SCOPE: Diets rich in fat and sugars evoke chronic low-grade inflammation, leading to metabolic derangements. This study investigates the impact of fructose and galactose, two commonly consumed simple sugars, on exacerbation of the harmful effects caused by high fat intake. Additionally, the potential efficacy of fructooligosaccharides (FOS), a fermentable dietary fiber, in counteracting these effects is examined. METHODS AND RESULTS: Male Sprague-Dawley rats (six/group) are fed 8 weeks as follows: control 5% fat diet (CNT), 20% fat diet (FAT), FAT+10% FOS diet (FAT+FOS), FAT+25% galactose diet (FAT+GAL), FAT+GAL+10% FOS diet (FAT+GAL+FOS), FAT+25% fructose diet (FAT+FRU), FAT+FRU+10% FOS diet (FAT+FRU+FOS). The dietary manipulations tested do not affect body weight gain, blood glucose, or markers of systemic inflammation whereas significant increases in plasma concentrations of triacylglycerols, cholesterol, aspartate aminotransferase, and alanine aminotrasferase are detected in both FAT+FRU and FAT+GAL compared to CNT. In the liver and skeletal muscle, both sugars induce significant accumulation of lipids and advanced glycation end-products (AGEs). FOS supplementation prevents these impairments. CONCLUSION: This study extends the understanding of the deleterious effects of a chronic intake of simple sugars and demonstrates the beneficial role of the prebiotic FOS in dampening the sugar-induced metabolic impairments by prevention of lipid and AGEs accumulation.

Disparities in health and nutrition between semi-urban and rural mothers and birth outcomes of their newborns in Bukavu, DR Congo: a baseline assessment.

AIM: This research aimed to evaluate health and nutritional practices of mothers during pregnancy and birth outcomes of their newborns in Bukavu, Democratic Republic of the Congo (DRC), comparing semi-urban and rural areas. BACKGROUND: Health and nutrition during pregnancy are crucial for adequate development of the fetus. Health care plays an important role but is often poor in rural areas of developing countries. METHODS: A baseline survey of a nutritional follow-up study was conducted in two semi-urban and one rural hospital in the vicinity of Bukavu, DRC. In total, 471 mother-child pairs were recruited after delivery. Data collection included socio-demographic parameters, nutrition and health measures during pregnancy, and anthropometric parameters. Semi-urban and rural study locations were compared and predictors of birth weight evaluated. FINDINGS: Semi-urban and rural mothers differed significantly in nutrition and health practices during pregnancy, as well as birth outcomes. In the rural area, there was a higher rate of newborns with low birth weight (10.7%) and lower rates of antimalarial medication (80.8%), deworming (24.6%), consumption of nutritional supplements (81.5%), and being informed about nutrition by medical staff (32.8%) during pregnancy as well as practicing family planning (3.1%) than in the semi-urban areas (2.7%, 88.6%, 88.3%; 89.3%, 46.5%, and 17.1%, respectively). Birth weight was positively predicted by increasing maternal MUAC, age, and gestational age and negatively by rural location, being primipara, being a farmer, and female newborn sex. CONCLUSION: The findings highlight the importance of strengthening antenatal care activities especially in rural areas in order to ameliorate both maternal and infantile health and ensure appropriate development.

Novel Biphasic In Vitro Dissolution Method Correctly Predicts the Oral Bioavailability of Curcumin in Humans.

In vitro dissolution methods correctly predicting in vivo bioavailability of compounds from complex mixtures are lacking. We therefore used data on the in vivo performance of bioavailability-improved curcumin formulations to implement an in vivo predictive dissolution method (BiPHa+). BiPHa+ was applied for the characterization of eight curcumin formulations previously studied in a strictly controlled pharmacokinetic human trial. During dissolution, the dissolved proportion of curcumin in the aqueous medium underwent a formulation-dependent reduction, whereas the proportion remained stable in the organic layer. Compared with conventional dissolution systems, BiPHa+ was superior in terms of in vivo-relevant formulation characterization. All formulations could be precisely categorized according to their bioavailability in humans. In vitro-in vivo relationships for each dissolution method were established, with BiPHa+ providing the highest degree of linearity (r2 = 0.9975). The BiPHa+ assay correctly predicted the bioavailability of curcuminoids from complex mixtures and provided mechanistic information about formulation-dependent release characteristics.

The Pharmacokinetics of Individual Conjugated Xanthohumol Metabolites Show Efficient Glucuronidation and Higher Bioavailability of Micellar than Native Xanthohumol in a Randomized, Double-Blind, Crossover Trial in Healthy Humans.

SCOPE: Prenylated chalcones and flavonoids are found in many plants and are believed to have beneficial effects on health when consumed. Xanthohumol is present in beer and likely the most consumed prenylated chalcone, but poorly absorbed and rapidly metabolized and excreted, thus limiting its bioavailability. Micellar formulations of phytochemicals have been shown to improve bioavailability. METHODS AND RESULTS: In a randomized, double-blind, crossover trial with five healthy (three males and two females) volunteers, a single dose of 43 mg was orally administered as a native or micellar formulation. The major human xanthohumol metabolites are quantified in plasma. Unmetabolized free xanthohumol makes 1% or less of total plasma xanthohumol. The area under the plasma concentration-time curve of xanthohumol-7-O-glucuronide following the ingestion of the micellular formulation is 5-fold higher and its maximum plasma concentration is more than 20-fold higher compared to native xanthohumol. CONCLUSION: Metabolism of orally ingested xanthohumol is complex and efficiently converts the parent compound to predominantly glucuronic acid and to a lesser extent sulfate conjugates. The oral bioavailability of micellar xanthohumol is superior to native xanthohumol, making it a useful delivery form for future human trials.

Effects of the DICE Method to Improve Timely Recognition and Treatment of Neuropsychiatric Symptoms in Early Alzheimer's Disease at the Memory Clinic: The BEAT-IT Study.

BACKGROUND: Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD) and are associated with negative outcomes. However, NPS are currently underrecognized at the memory clinic and non-pharmacological interventions are scarcely implemented. OBJECTIVE: To evaluate the effectiveness of the Describe, Investigate, Create, Evaluate (DICE) method™ to improve the care for NPS in AD at the memory clinic. METHODS: We enrolled sixty community-dwelling people with mild cognitive impairment or AD dementia and NPS across six Dutch memory clinics with their caregivers. The first wave underwent care as usual (n = 36) and the second wave underwent the DICE method (n = 24). Outcomes were quality of life (QoL), caregiver burden, NPS severity, NPS-related distress, competence managing NPS, and psychotropic drug use. Reliable change index was calculated to identify responders to the intervention. A cost-effectiveness analysis was performed and semi-structured interviews with a subsample of the intervention group (n = 12). RESULTS: The DICE method did not improve any outcomes over time compared to care as usual. Half of the participants of the intervention group (52%) were identified as responders and showed more NPS and NPS-related distress at baseline compared to non-responders. Interviews revealed substantial heterogeneity among participants regarding NPS-related distress, caregiver burden, and availability of social support. The intervention did not lead to significant gains in quality-adjusted life years and well-being years nor clear savings in health care and societal costs. CONCLUSION: The DICE method showed no benefits at group-level, but individuals with high levels of NPS and NPS-related distress may benefit from this intervention.

Dysfunctional Voiding: Exploring Disease Transition From Childhood to Adulthood.

OBJECTIVE: To improve our transitional care, we explored how childhood dysfunctional voiding (DV) develops into adulthood. DV is a common condition in both children and adults. However, the long-term course of childhood DV into adulthood is unknown and treatment over the ages differs. METHODS: A cross-sectional follow-up was performed in a cohort of 123 females treated from 2000 to 2003 for childhood DV with urinary tract infections (UTIs) and/or daytime urinary incontinence (DUI). The main outcome was a staccato or intermittent urinary flow pattern, possibly indicating persistent or recurred DV according to the International Continence Society criteria. Flow patterns of healthy women were used to compare results. RESULTS: Twenty-five patients participated in this study, with a mean duration of 20.8 years after urotherapy. In 10/25 (40%) cases, a staccato or interrupted urinary flow pattern was found on the current measurement, compared to 5/47 (10.6%) in the control group. Around 50% (5/10) of the patients with a dysfunctional flow pattern reported UTIs and 50% (5/10) experienced DUI. In the group with a normal flow pattern, 2/15 (13%) reported UTIs and 9/15 (60%) DUI. The impact of DUI on quality of life was moderate to high in both groups. CONCLUSION: Our results show that 40% of females who had extensive urotherapy for DV in childhood, still have DV according to International Continence Society criteria as an adult, 56% still experience DUI, and 28% UTIs. These data should be taken into account in the counseling of patients and for guiding the process of transition into adulthood.

Prostate cancer risk assessment by the primary care physician and urologist: transabdominal- versus transrectal ultrasound prostate volume-based use of the Rotterdam Prostate Cancer Risk Calculator.

Background: Our objective was to assess the accuracy of transabdominal ultrasound (TAUS) measured prostate volume in the primary care setting with transrectal ultrasound (TRUS) measured prostate volume by the urologist as the reference test. Furthermore, our objective was to assess whether risk-stratification using TAUS prostate volume by the primary care physician could reduce unnecessary referrals to the urologist. Methods: Men in two Dutch primary care offices with a prostate cancer (PCa) screening request received a digital rectal examination (DRE), prostate specific-antigen (PSA), and TAUS prostate volume measurement by the general practitioner, followed by Rotterdam Prostate Cancer Risk Calculator (RPCRC) risk assessment. The examination was repeated by a urologist using TRUS. A prostate biopsy was performed in case of a RPCRC positive biopsy advice. A non-inferiority analysis was performed comparing TAUS and TRUS prostate volume differences. A risk-based referral strategy using TAUS and the RPCRC in the primary care setting was compared with the standard referral strategy based on PSA (≥3 ng/mL) and DRE. Results: A total of 105 men were included with a median PSA of 1.9 ng/mL. The mean prostate volumes measured by TAUS and TRUS were 55 and 45 mL, respectively. The mean overestimation of the prostate volume by TAUS as compared to the reference test was 9.9 mL (95% CI: 5.9-13.8). According to Dutch standard practice, 41 out of 105 (39%) men would have been referred to the urologist. Stratification in primary care based on the RPCRC using TAUS prostate volume would have avoided 29 out of the 41 (71%) referrals, at the expense of non-referral of 5 out of 11 (45%) men with a biopsy indication, according to the urologist. Conclusions: RPCRC-based risk stratification in primary care using TAUS prostate volume measurement is feasible and may prevent unnecessary referrals to the urologist and reduce costs. The accuracy of the risk assessment with TAUS might be improved by sufficient training and centralization to achieve a higher volume of consultations in primary care facilities.

Optimization of Supercritical Carbon Dioxide Extraction of Polyphenols from Black Rosehip and Their Bioaccessibility Using an In Vitro Digestion/Caco-2 Cell Model.

The fruits of Rosa pimpinellifolia are rich sources of (poly)phenols, however they are underutilized due to the limited information available. The influence of the pressure, temperature, and co-solvent concentration (aqueous ethanol) of the supercritical carbon dioxide extraction (SCO2-aqEtOH) on the extraction yield, total phenolic-, total anthocyanin-, catechin-, cyanidin-3-O-glucoside contents, and total antioxidant activity of black rosehip was investigated simultaneously. The maximum obtained total phenolic and total anthocyanin contents under the optimized extraction conditions (280 bar, 60 °C and 25% ethanol, v/v) were 76.58 ± 4.25 mg gallic acid equivalent and 10.89 ± 1.56 mg cyanidin-3-O-glucoside equivalent per g of the dry fruits, respectively. The optimal extract obtained by SCO2-aqEtOH was compared to two other extraction procedures: ultrasonication using ethanol as solvent (UA-EtOH) and pressurized hot water extraction (PH-H2O). The bioaccessibility and cellular metabolism of the phenolic compounds in the different black rosehip extracts were assessed using an in vitro digestion coupled with a human intestinal Caco-2 cell model. The in vitro digestive stability and cellular uptake of the phenolic compounds had no significant difference among the different extraction methods. The results of this study confirm the efficiency of SCO2-aqEtOH extraction for phenolic compounds and, in particular, for anthocyanins, and could be used to produce new functional food ingredients from black rosehip with high antioxidant power containing both hydrophilic and lipophilic compounds.