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.

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.

Food insecurity, low dietary diversity and poor mental health among Syrian refugee mothers living in vulnerable areas of Greater Beirut, Lebanon.

Syrian refugees in Lebanon are facing vulnerabilities that are affecting their food insecurity (FI) levels. The objectives of this study were to measure dietary diversity, FI and mental health status of Syrian refugee mothers in Lebanon and to explore its associations with their anaemia and nutritional status. A cross-sectional study was conducted among mothers with children under 5 years (n 433) in Greater Beirut, Lebanon. Dietary diversity was measured using the Minimum Dietary Diversity for Women (MDD-W) of reproductive age and FI using the global Food Insecurity Experience Scale at the individual level. Depression and post-traumatic stress disorder (PTSD) were measured to assess the maternal mental health status. Data on socio-economic characteristics, anthropometric measurements and Hb concentrations were collected. Overall, 63·3 % of the mothers had a low dietary diversity (LDD) and 34·4 % were moderately to severely food insecure, with 12·5 % being severely food insecure. The prevalence of PTSD, moderate depression and severe depression was 13·2, 11·1 and 9·9 %, respectively. A significant correlation was found between LDD and FI (P < 0·001). Low income was significantly associated with LDD and FI. Poor mental health was significantly associated with FI. LDD and FI were not associated with anaemia and nutritional status of mothers. Low-income households had significantly higher intakes of grains and refined starchy staples, whereas high-income households consumed more nutritious foods and sweets. Evidence of inadequate diet quality, FI and poor mental health among Syrian refugee mothers in Lebanon is presented. Multifaceted actions are needed to reduce FI and improve dietary diversity.

Association between fat-soluble vitamins and self-reported health status: a cross-sectional analysis of the MARK-AGE cohort.

Self-rated health (SRH) is associated with higher risk of death. Since low plasma levels of fat-soluble vitamins are related to mortality, we aimed to assess whether plasma concentrations of vitamins A, D and E were associated with SRH in the MARK-AGE study. We included 3158 participants (52 % female) aged between 35 and 75 years. Cross-sectional data were collected via questionnaires. An enzyme immunoassay quantified 25-hydroxyvitamin D and HPLC determined α-tocopherol and retinol plasma concentrations. The median 25-hydroxyvitamin D and retinol concentrations differed significantly (P < 0·001) between SRH categories and were lower in the combined fair/poor category v. the excellent, very good and good categories (25-hydroxvitamin D: 40·8 v. 51·9, 49·3, 46·7 nmol/l, respectively; retinol: 1·67 v. 1·75, 1·74, 1·70 µmol/l, respectively). Both vitamin D and retinol status were independently associated with fair/poor SRH in multiple regression analyses: adjusted OR (95 % CI) for the vitamin D insufficiency, deficiency and severe deficiency categories were 1·33 (1·06-1·68), 1·50 (1·17-1·93) and 1·83 (1·34-2·50), respectively; P = 0·015, P = 0·001 and P < 0·001, and for the second/third/fourth retinol quartiles: 1·44 (1·18-1·75), 1·57 (1·28-1·93) and 1·49 (1·20-1·84); all P < 0·001. No significant associations were reported for α-tocopherol quartiles. Lower vitamin A and D status emerged as independent markers for fair/poor SRH. Further insights into the long-term implications of these modifiable nutrients on health status are warranted.

Associations of 24 h urinary excretions of α- and γ-carboxyethyl hydroxychroman with plasma α- and γ-tocopherol and dietary vitamin E intake in older adults: the Lifelines-MINUTHE Study.

BACKGROUND: Urinary metabolites of vitamin E, i.e., α- and γ-carboxyethyl hydroxychroman (α- and γ-CEHC), have gained increasing attention and have been proposed as novel biomarkers of vitamin E intake and status. However, there are insufficient data on the relationship of plasma α-tocopherol and γ-tocopherol and dietary vitamin E intake with 24 h urinary excretions of α- and γ-CEHC. OBJECTIVES: We aimed to (1) investigate the associations of urinary α- and γ-CEHC/creatinine ratios and 24 h urinary excretions of α- and γ-CEHC with plasma α- and γ-tocopherol, respectively; (2) investigate the associations of urinary α- and γ-CEHC/creatinine ratios and 24 h urinary excretions of α- and γ-CEHC with dietary vitamin E intake, and we hypothesize that 24 h urinary excretions of α- and γ-CEHC will better correlate with vitamin E intake than urinary α- and γ-CEHC/creatinine ratios. DESIGN: 24 h Urine and plasma samples were collected from 1519 participants (60-75 years, male: 50%) included in the Lifelines-MINUTHE Study for the assessments of urinary α- and γ-CEHC/creatinine ratios and 24 h urinary excretions of α- and γ-CEHC, and plasma α- and γ-tocopherol. Among those participants, dietary vitamin E intake data from 387 participants were available from an externally validated Flower-Food Frequency Questionnaire (FFQ). The associations of plasma α- and γ-tocopherol, dietary vitamin E intake, with urinary α- and γ-CEHC were assessed using multivariate linear regressions. RESULTS: 24 h Urinary excretion of α-CEHC (median (IQR): 0.9 (0.3-2.4) µmol) was less than that of γ-CEHC (median (IQR): 1.5 (0.5-3.5) µmol). After adjustment for covariates, we found that 24 h urinary α-CEHC excretion and urinary α-CEHC/creatinine ratio were both positively associated with plasma α-tocopherol (std.beta: 0.06, p = 0.02; std.beta: 0.06, p = 0.01, respectively). Furthermore, the sum of 24 h urinary α- and γ-CEHC excretions was positively associated with dietary vitamin E intake (std.beta: 0.08; p = 0.03), whereas there was no relation between urinary α- and γ-CEHC/creatinine ratios and vitamin E intake. No association was observed neither between plasma α- and γ-tocopherol and dietary vitamin E intake, nor between urinary γ-CEHC and plasma γ-tocopherol. CONCLUSION: Our study confirmed our hypothesis that 24 h urinary α- and γ-CEHC excretions would be a better marker for dietary vitamin E intake than urinary α- and γ-CEHC/creatinine ratios. Considering that both 24 h urinary α- and γ-CEHC excretions and α- and γ-CEHC/creatinine ratios were also associated with plasma α-tocopherol status, we suggest that 24 h urinary α- and γ-CEHC excretions could be used to assess overall vitamin E status.

Biweekly fluctuations of neuropsychiatric symptoms according to the Neuropsychiatric Inventory: Erratic symptoms or scores?

OBJECTIVES: This study investigates the stability of neuropsychiatric symptoms (NPS) assessed biweekly using the Neuropsychiatric Inventory (NPI) in a memory clinic population during a 6 week period. METHODS: Twenty-three spousal caregivers (mean [SD] age = 69.7 [8.8], 82.6% female) of 23 patients (43.5% had dementia) completed all assessments. The NPI was assessed four times during 6 weeks. We examined whether NPI domains were present during all four assessments, studied within-person variation for each NPI domain, and calculated Spearman's correlations between subsequent time-points. Furthermore, we associated repeated NPI assessments with repeated measures of caregiver burden to examine the clinical impact of changes in NPI scores over time. RESULTS: The course of NPS was highly irregular according to the NPI, with only 35.8% of the NPI domains that were present at baseline persisted during all 6 weeks. We observed large within-person variation in the presence of individual NPI domains (61.3%, range 37.5%-83.9%) and inconsistent correlations between NPI assessments (e.g., range rs  = 0.20-0.57 for agitation, range rs  = 0.29-0.59 for anxiety). Higher NPI total scores were related to higher caregiver burden (rs  = 0.60, p < 0.001), but changes in NPI total scores were unrelated to changes in caregiver burden (rs  = 0.16, p = 0.20). CONCLUSIONS: We observed strong fluctuations in NPI scores within very short time windows raising the question whether this represents erratic symptoms and/or scores. Further studies are needed to investigate the origins of these fluctuations.

Potentially Beneficial Effects on Healthy Aging by Supplementation of the EPA-Rich Microalgae Phaeodactylum tricornutum or Its Supernatant-A Randomized Controlled Pilot Trial in Elderly Individuals.

Dietary supplements that promote healthy aging are mostly warranted in an aging society. Because of age-related risks, anti-inflammatory and anti-oxidative agents such as microalgae are potential candidates for intervention. In a randomized controlled trial, we tested Phaeodactylum tricornutum (PT), a microalgae rich in eicosapentaenoic acid (EPA), carotenoids, vitamins, and ß-glucans, cultured in bioreactors. In this pilot trial, 19 healthy elderly received supplements for two weeks based on either the whole PT (A), the ß-1,3-glucan-rich PT supernatant (SupB), the combination thereof (A+SupB), or a Comparator product (Comp). The primary outcome variable plasma interleukin-6 was reduced after treatment with A+SupB compared to the Comp group (p = 0.04). The mobility parameters 5 s sit-to-stand test (p = 0.04 in the A group) and by trend gait speed (p = 0.08 in the A+SupB diet) were improved compared to Comp. No treatment effects were observed for fatty acids, compared to Comp but omega-6 to -3 fatty acid ratio (p = 0.006) and arachidonic acid/EPA ratio (p = 0.006) were reduced within group A+SupB. Further, the SupB study product reduced faecal zonulin (p = 0.03) compared to the Comp. The data revealed an anti-inflammatory and potentially anti-oxidative effect of particular PT preparations, suggesting that they might be suitable for effects in healthy elderly.

Antioxidants Attenuate Heat Shock Induced Premature Senescence of Bovine Mesenchymal Stem Cells.

Mesenchymal stem cells (MSC) have many roles that are important for the body's proper functioning. When the MSC pool is damaged, it is often correlated with impaired development or health of the organism. MSC are known for their anti-inflammatory, immunomodulatory and trophic characteristics that play an important role in the physiological homeostasis of many tissues. Heat shock impairs MSC capacity by inducing the generation of reactive oxygen species and mitochondrial dysfunction, which, in turn, send the cells into a state of premature senescence. Here, we pre-exposed MSC to melatonin, resveratrol, or curcumin, which are natural antioxidative compounds, and tested the protective effects of these substances from oxidative stress and aging. Our data showed that pre-exposure of MSC to antioxidants decreased reactive oxygen species while mitochondrial damage remained high. Additionally, although the proliferation of the cells was slow, antioxidants protected the cells from premature senescence, and subsequent cytokine release was prevented. We conclude that while elevated temperatures directly cause mitochondrial damage, senescence is induced by elevated ROS levels. We suggest that heat shock alters cell and tissue homeostasis by several independent mechanisms; however, reducing tissue senescence will reduce damage and provide a pathway to overcome physiological challenges in animals.

Recovery of Polyphenols Using Pressurized Hot Water Extraction (PHWE) from Black Rosehip Followed by Encapsulation for Increased Bioaccessibility and Antioxidant Activity.

In this work, pressurized hot water extraction (PHWE) of hydrophilic polyphenols from black rosehip fruit was maximized using response surface methodology for simultaneous optimization in terms of extraction yield, total antioxidant capacity, total (poly)phenols, catechin, total monomeric anthocyanins, and cyanidin-3-O-glucoside. Extraction parameters, including temperature (X1: 40-80 °C) and the solvent-to-solid ratio (X2: 10-40 mL/g), were investigated as independent variables. Experimentally obtained values were fitted to a second-order polynomial model, and optimal conditions were determined using multiple regression analysis and analysis of variance. The black rosehip extract (BRE) obtained at optimized PHWE conditions was further encapsulated in biopolymer-coated liposomes and spray dried to enhance its processing and digestive stability. After reconstitution, the fabricated particles had an average size of 247-380 nm and a zeta-potential of 15-45 mV. Moreover, encapsulation provided remarkable protection of the phenolics under in vitro gastrointestinal digestion conditions, resulting in up to a 5.6-fold more phenolics in the bioaccessible fraction, which also had 2.9-8.6-fold higher antioxidant activity compared to the nonencapsulated BRE. In conclusion, PHWE in combination with a biopolymer coating is a potent method for the production of stable and safe edible natural extracts for the delivery of (poly)phenolic compounds in food and dietary supplements.

Vitamin E and carotenoid profiles in leaves, stems, petioles and flowers of stinging nettle (Urtica leptophylla Kunth) from Costa Rica.

BACKGROUND: Local leafy vegetables are gaining attention as affordable sources of micronutrients, including vitamins, pro-vitamin carotenoids and other bioactive compounds. Stinging nettles (Urtica spp.) are used as source of fibers, herbal medicine and food. However, despite the relatively wide geographical spread of Urtica leptophylla on the American continent, little is known about its content of vitamin E congeners and carotenoids. We therefore investigated the particular nutritional potential of different plant structures of wild Costa Rican U. leptophylla by focusing on their vitamin E and carotenoid profiles. RESULTS: Young, mature and herbivore-damaged leaves, flowers, stems and petioles were collected and freeze-dried. Vitamin E and carotenoids were determined by high-performance liquid chromatography after liquid/liquid extraction with hexane. α-Tocopherol was the major vitamin E congener in all structures. Flowers had a high content of γ-tocopherol. Herbivore-damaged leaves had higher contents of vitamin E than undamaged leaves. Lutein was the major and ß-carotene the second most abundant carotenoid in U. leptophylla. No differences in carotenoid profiles were observed between damaged and undamaged leaves. CONCLUSION: The leaves of U. leptophylla had the highest nutritional value of all analyzed structures; therefore, they might represent a potential source of α-tocopherol, lutein and ß-carotene. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Curcumin Administered as Micellar Solution Suppresses Intestinal Inflammation and Colorectal Carcinogenesis.

Colorectal cancer (CRC) is one of the most common cancers and preventive strategies based on natural compounds are highly desirable. Curcumin, the principal bioactive compound in Curcuma longa, was described to have multiple beneficial health effects. A drawback, however, is the low bioavailability due to its insolubility in water. Here, we studied whether nanoscaled micellar curcumin with improved bioavailability administered in drinking water reduces inflammation and CRC formation in a mouse model. C57BL6 wild-type (WT) mice and a strain defective in the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) were used, in which tumors were induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS). Inflammation and tumor formation were determined by mini-colonoscopy. Micellar curcumin (mCur) administered in drinking water significantly reduced AOM/DSS-induced colorectal inflammation in both WT and MGMT-deficient mice as compared to animals receiving drinking water with micelles not containing curcumin. In line with this, the tumor yield and tumor score were significantly lower in mCur-treated mice compared to the control group. No adverse effects were observed in animals receiving mCur daily for at least three months. Overall, our data show that chronic oral administered micellar curcumin is well tolerated and reduces chemical-induced gut inflammation and CRC formation in mice.Impact: The study shows that micellar curcumin with high bioavailability chronically administered at low and physiologically relevant concentration suppresses inflammation and carcinogenesis in a mouse colorectal tumor model.

Oral Bioavailability of Omega-3 Fatty Acids and Carotenoids from the Microalgae Phaeodactylum tricornutum in Healthy Young Adults.

The microalgae Phaeodactylum tricornutum (PT) contains valuable nutrients such as proteins, polyunsaturated omega-3 fatty acids (n-3 PUFA), particularly eicosapentaenoic acid (EPA) and some docosahexaenoic acid (DHA), carotenoids such as fucoxanthin (FX), and beta-glucans, which may confer health benefits. In a randomized intervention trial involving 22 healthy individuals, we administered for two weeks in a crossover manner the whole biomass of PT (5.3 g/day), or fish oil (FO) containing equal amounts of EPA and DHA (together 300 mg/day). In an additional experiment, sea fish at 185 g/week resulting in a similar EPA and DHA intake was administered in nine individuals. We determined the bioavailability of fatty acids and carotenoids and assessed safety parameters. The intake of PT resulted in a similar increase in the n-3 PUFA and EPA content and a decrease in the PUFA n-6:n-3 ratio in plasma. PT intake caused an uptake of FX that is metabolized to fucoxanthinol (FXOH) and amarouciaxanthin A (AxA). No relevant adverse effects occurred following PT consumption. The study shows that PT is a safe and effective source of EPA and FX-and likely other nutrients-and therefore should be considered as a future sustainable food item.

Comparative Analysis of the Antitumor Activity of Cis- and Trans-Resveratrol in Human Cancer Cells with Different p53 Status.

Resveratrol, a natural plant phytoalexin, is produced in response to fungal infection or- UV irradiation. It exists as an isomeric pair with cis- and trans-conformation. Whereas multiple physiological effects of the trans-form, including a pronounced anti-tumoral activity, are nowadays elucidated, much less knowledge exists concerning the cis-isomer. In our work, we analyzed the antiproliferative and cytotoxic properties of cis-resveratrol in four different human tumor entities in direct comparison to trans-resveratrol. We used human cell lines as tumor models for hepatocellular carcinoma (HCC; HepG2, Hep3B), colon carcinoma (HCT-116, HCT-116/p53(-/-)), pancreatic carcinoma (Capan-2, MiaPaCa-2), and renal cell carcinoma (A498, SN12C). Increased cytotoxicity in all investigated tumor cells was observed for the trans-isomer. To verify possible effects of the tumor suppressor p53 on resveratrol-induced cell death, we used wild type and p53-deleted or -mutated cell lines for every tested tumor entity. Applying viability and cytotoxicity assays, we demonstrated a differential, dose-dependent sensitivity towards cis- or trans-resveratrol among the respective tumor types.

Prostate cancer upgrading with serial prostate magnetic resonance imaging and repeat biopsy in men on active surveillance: are confirmatory biopsies still necessary?

OBJECTIVES: To investigate whether serial prostate magnetic resonance imaging (MRI) may guide the utility of repeat targeted (TBx) and systematic biopsy (SBx) when monitoring men with low-risk prostate cancer (PCa) at 1-year of active surveillance (AS). PATIENTS AND METHODS: We retrospectively included 111 consecutive men with low-risk (International Society of Urological Pathology [ISUP] Grade 1) PCa, who received protocolled repeat MRI with or without TBx and repeat SBx at 1-year of AS. TBx was performed in Prostate Imaging-Reporting and Data System (PI-RADS) score ≥3 lesions (MRI-positive men). Upgrading defined as ISUP Grade ≥2 PCa (I), Grade ≥2 with cribriform growth/intraductal carcinoma PCa (II), and Grade ≥3 PCa (III) was investigated. Upgrading detected by TBx only (not by SBx) and SBx only (not by TBx) was investigated in MRI-positive and -negative men, and related to radiological progression on MRI (Prostate Cancer Radiological Estimation of Change in Sequential Evaluation [PRECISE] score). RESULTS: Overall upgrading (I) was 32% (35/111). Upgrading in MRI-positive and -negative men was 48% (30/63) and 10% (5/48) (P < 0.001), respectively. In MRI-positive men, there was upgrading in 23% (seven of 30) by TBx only and in 33% (10/30) by SBx only. Radiological progression (PRECISE score 4-5) in MRI-positive men was seen in 27% (17/63). Upgrading (I) occurred in 41% (seven of 17) of these MRI-positive men, while this was 50% (23/46) in MRI-positive men without radiological progression (PRECISE score 1-3) (P = 0.534). Overall upgrading (II) was 15% (17/111). Upgrading in MRI-positive and -negative men was 22% (14/63) and 6% (three of 48) (P = 0.021), respectively. In MRI-positive men, there was upgrading in three of 14 by TBx only and in seven of 14 by SBx only. Overall upgrading (III) occurred in 5% (five of 111). Upgrading in MRI-positive and -negative men was 6% (four of 63) and 2% (one of 48) (P = 0.283), respectively. In MRI-positive men, there was upgrading in one of four by TBx only and in two of four by SBx only. CONCLUSION: Upgrading is significantly lower in MRI-negative compared to MRI-positive men with low-risk PCa at 1-year of AS. In serial MRI-negative men, the added value of repeat SBx at 1-year surveillance is limited and should be balanced individually against the harms. In serial MRI-positive men, the added value of repeat SBx is substantial. Based on this cohort, SBx is recommended to be performed in combination with TBx in all MRI-positive men at 1-year of AS, also when there is no radiological progression.

Dementia With Lewy Bodies: A Clinicopathologic Series of False-positive Cases.

Diagnosing dementia with Lewy bodies (DLB) is challenging as symptoms are heterogenous and not specific to the disease. Here we present a clinicopathologic series of false-positive DLB cases. Patients were enrolled retrospectively from the Netherlands Brain Bank when they met the clinical criteria of probable DLB, but with a pathologic diagnosis other than DLB or Parkinson's disease dementia. Twenty-two false-positive cases were selected. Alzheimer disease with or without copathology was the most common (64%) pathologic diagnosis. Other pathologic diagnoses, such as frontotemporal dementia, multiple-system atrophy, Creutzfeldt-Jakob disease, and autoimmune encephalitis, were also encountered. Atypical clinical signs for DLB were present in almost half of the cases and could be a trigger to consider other diagnoses than DLB. Additional diagnostic examinations, feedback of pathologic diagnosis, and the creation of a set of clinical features that are indicative of other conditions, could reduce the amount of false-positive DLB cases.

What factors are associated with maternal undernutrition in eastern zone of Tigray, Ethiopia? Evidence for nutritional well-being of lactating mothers.

BACKGROUND: Maternal undernutrition is a pervasive health problem among Ethiopian mothers. This study aims at identifying the level of maternal undernutrition and its associated factors in Kilte Awaleo-Health and Demographic Surveillance Site (KA-HDSS), Tigray region, Ethiopia. METHODS: Nutritional status of 2260 lactating mothers was evaluated using the mid-upper-arm circumference (MUAC). Data from the vital events and verbal autopsy databases were linked to the survey and baseline recensus data to investigate the association of adult mortality from chronic causes of death (CoD) on maternal undernutrition. We employed a generalized log-binomial model to estimate the independent effects of the fitted covariates. RESULTS: The overall prevalence of maternal undernutrition based on MUAC < 23 cm was 38% (95% CI: 36.1, 40.1%). Recent occurrence of household morbidity (adjusted prevalence ratio (adjPR) = 1.49; 95%CI: 1.22, 1.81) was associated with increased risk of maternal undernutrition. In addition, there was a 28% higher risk (adjPR = 1.28; 95%CI: 0.98, 1.67) of maternal undernutrition for those mothers who lived in households with history of adult mortality from chronic diseases. Especially, its association with severe maternal undernutrition was strong (adjusted OR = 3.27; 95%CI: 1.48, 7.22). In contrast, good maternal health-seeking practice (adjPR = 0.86; 95%CI: 0.77, 0.96) and production of diverse food crops (adjPR = 0.72; 95%CI: 0.64, 0.81) were associated with a lower risk of maternal undernutrition. Relative to mothers with low scores of housing and environmental factors index (HAEFI), those with medium and higher scores of HAEFI had 0.81 (adjPR = 0.81; 95%CI: 0.69, 0.95) and 0.82 (adjPR = 0.82; 95%CI: 0.72, 0.95) times lower risk of maternal undernutrition, respectively. CONCLUSIONS: Efforts to ameliorate maternal undernutrition need to consider the influence of the rising epidemiology of adult mortality from chronic diseases. Our data clearly indicate the need for channeling the integrated intervention power of nutrition-sensitive development programs with that of nutrition-specific sectoral services.

α-Tocomonoenol Is Bioavailable in Mice and May Partly Be Regulated by the Function of the Hepatic α­Tocopherol Transfer Protein.

Tocomonoenols are vitamin E derivatives present in foods with a single double bond at carbon 11' in the sidechain. The α-tocopherol transfer protein (TTP) is required for the maintenance of normal α-tocopherol (αT) concentrations. Its role in the tissue distribution of α-11'-tocomonoenol (αT1) is unknown. We investigated the tissue distribution of αT1 and αT in wild-type (TTP+/+) and TTP knockout (TTP-/-) mice fed diets with either αT or αT1 for two weeks. αT1 was only found in blood, not tissues. αT concentrations in TTP+/+ mice were in the order of adipose tissue > brain > heart > spleen > lungs > kidneys > small intestine > liver. Loss of TTP function depleted αT in all tissues. αT1, contrary to αT, was still present in the blood of TTP-/- mice (16% of αT1 in TTP+/+). Autoclaving and storage at room temperature reduced αT and αT1 in experimental diets. In conclusion, αT1 is bioavailable, reaches the blood in mice, and may not entirely depend on TTP function for secretion into the systemic circulation. However, due to instability of the test compounds in the experimental diets, further in vivo experiments are required to clarify the role of TTP in αT1 secretion. Future research should consider compound stability during autoclaving of rodent feed.

The Coconut Water Antimicrobial Peptide CnAMP1 Is Taken up into Intestinal Cells but Does Not Alter P-Glycoprotein Expression and Activity.

Coconut antimicrobial peptide-1 (CnAMP1) is a naturally occurring bioactive peptide from green coconut water (Cocos nucifera L.). Although biological activities have been reported, the physiological relevance of these reports remains elusive as it is unknown if CnAMP1 is taken up into intestinal cells. To address this open question, we investigated the cytotoxicity of CnAMP1 in intestinal cells and its cellular uptake into human intestinal cells. Considering the importance of the P-glycoprotein (P-gp) to the intestinal metabolism of xenobiotics, we also investigated the influence of CnAMP1 on P-gp activity and expression. Both cell lines showed intracellular fluorescence after incubation with fluorescein labelled CnAMP1, indicating cellular uptake of the intact or fragmented peptide. CnAMP1 (12.5-400 µmol/L) showed no signs of cytotoxicity in LS180 and differentiated Caco-2 cells and did not affect P-gp expression and activity. Further research is required to investigate the identity of CnAMP1 hydrolysis fragments and their potential biological activities.

Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia.

BACKGROUND: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD. METHODS: This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset). RESULTS: CSF NfL levels were significantly higher in patients with SD (median: 2326 pg/mL, IQR: 1628-3593) than in controls (577 (446-766), p<0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test (rs =-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (rs =-0.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival. CONCLUSION: CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities.