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Introduction: Transcranial Doppler (TCD) sonography is a noninvasive tool for measuring cerebrovascular hemodynamics. Studies have reported alterations in cerebrovascular hemodynamics in normal aging, mild cognitive impairment (MCI), and dementia, as well as in different etiologies of dementia. This systematic review and meta-analysis was designed to investigate the relationship between cerebral blood velocity (CBv) and pulsatility index (PI) in the middle cerebral artery (MCA) in persons with MCI and dementia. Methods: A systematic literature search was conducted in Pubmed, Embase, Cochrane Library, Epistemonikos, PsychINFO, and CINAHL. The search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. After screening of 33,439 articles, 86 were reviewed in full-text, and 35 fulfilled the inclusion criteria. Results: CBv was significantly lower and PI significantly higher in MCA in vascular dementia (VaD) and Alzheimer's disease (AD) compared to cognitively normal (CN) older persons. Also, CBv was lower in MCI compared to CN. There were no significant differences in CBv in MCA in AD compared with VaD, although PI was higher in VaD compared to AD. Conclusion: Alterations in cerebrovascular hemodynamics are seen in AD, VaD, and MCI. While PI was slightly higher in VaD compared to AD, the reduction in CBv appears to be equally pronounced across neurodegenerative and vascular etiologies of dementia. [ABSTRACT FROM AUTHOR]

Background and Purpose: Over past decades, targeted therapies and immunotherapy have improved survival and reduced the morbidity of patients with BRAF-mutated melanoma. However, drug resistance and relapse hinder overall success. Therefore, there is an urgent need for novel compounds with therapeutic efficacy against BRAF-melanoma. This prompted us to investigate the antiproliferative profile of a tachykinin-peptide from the Octopus kaurna, Octpep-1 in melanoma.Experimental Approach: We evaluated the cytotoxicity of Octpep-1 by MTT assay. Mechanistic insights on viability and cellular damage caused by Octpep-1 were gained via flow cytometry and bioenergetics. Structural and pharmacological characterization was conducted by molecular modelling, molecular biology, CRISPR/Cas9 technology, high-throughput mRNA and calcium flux analysis. In vivo efficacy was validated in two independent xerograph animal models (mice and zebrafish).Key Results: Octpep-1 selectively reduced the proliferative capacity of human melanoma BRAFV600E -mutated cells with minimal effects on fibroblasts. In melanoma-treated cells, Octpep-1 increased ROS with unaltered mitochondrial membrane potential and promoted non-mitochondrial and mitochondrial respiration with inefficient ATP coupling. Molecular modelling revealed that the cytotoxicity of Octpep-1 depends upon the α-helix and polyproline conformation in the C-terminal region of the peptide. A truncated form of the C-terminal end of Octpep-1 displayed enhanced potency and efficacy against melanoma. Octpep-1 reduced the progression of tumours in xenograft melanoma mice and zebrafish.Conclusion and Implications: We unravel the intrinsic anti-tumoural properties of a tachykinin peptide. This peptide mediates the selective cytotoxicity in BRAF-mutated melanoma in vitro and prevents tumour progression in vivo, providing a foundation for a therapy against melanoma. [ABSTRACT FROM AUTHOR]

Alkylresorcinols (ARs, 5-n-alkylresorcinols) are amphiphilic phenolic lipids in whole grain rye and wheat, with a long odd-numbered carbon chain. A preventive effect of whole grain diet on sex hormone-dependent cancers has been recognized, but the active component(s) or mechanisms are not known. We have investigated the effects of the ARs C15:0, C19:0, and C21:0, individually and in combination, on steroid hormone production by using the human adrenocortical cell line H295R. Decreased synthesis of dehydroepiandrosterone (DHEA), testosterone, and estradiol was demonstrated at low concentrations of C15:0 and C19:0. There were no indications of additive effects on steroid secretion from the combined treatment with equimolar concentrations of the three ARs. Gene expressions of CYP21A2, HSD3B2, and CYP19A1 were downregulated and CYP11A1 was upregulated by the ARs. The results on gene expression could not explain the effects on steroidogenesis, which may be due to direct effects on enzyme activities, such as inhibition of CYP17A1. Our results demonstrate suppressed synthesis of testosterone and estradiol by ARs suggesting a novel mechanism for ARs in the chemoprevention of prostate and breast cancer. [ABSTRACT FROM AUTHOR]

Background: Determinants of vitamin D status measured as 25-OH-vitamin D in blood are exposure to sunlight and intake of vitamin D through food and supplements. It is unclear how large the contributions are from these determinants in Swedish primary care patients, considering the low radiation of UVB in Sweden and the fortification of some foods. Asian and African immigrants in Norway and Denmark have been found to have very low levels, but it is not clear whether the same applies to Swedish patients. The purpose of our study was to identify contributors to vitamin D status in Swedish women attending a primary health care centre at latitude 60°N in Sweden. Methods: In this cross-sectional, observational study, 61 female patients were consecutively recruited between January and March 2009, irrespective of reason for attending the clinic. The women were interviewed about their sun habits, smoking, education and food intake at a personal appointment and blood samples were drawn for measurements of vitamin D and calcium concentrations. Results: Plasma concentration of 25-OH-vitamin D below 25 nmol/L was found in 61% (19/31) of immigrant and 7% (2/30) of native women. Multivariate analysis showed that reported sun holiday of one week during the last year at latitude below 40°N with the purpose of sun-bathing and native origin, were significantly, independently and positively associated with 25-OH-vitamin D concentrations in plasma with the strongest association for sun holiday during the past year. Conclusions: Vitamin D deficiency was common among the women in the present study, with sun holiday and origin as main determinants of 25-OH-vitamin D concentrations in plasma. Given a negative effect on health this would imply needs for vitamin D treatment particularly in women with immigrant background who have moved from lower to higher latitudes. [ABSTRACT FROM AUTHOR]

Background: Immigration to Sweden from lower latitude countries has increased in recent years. Studies in the general population in other Nordic countries have demonstrated that these groups are at risk of developing vitamin D deficiency, but studies in primary health care patients are rare. Objectives: The aim of this study is to examine possible differences in plasma-25(OH)-vitamin D levels and intake of vitamin D between Swedish and immigrant female patients in a primary health care centre located at 60°N, where half of the inhabitants have an immigrant background. Another objective was to estimate what foods contribute with most vitamin D. Design: Thirty-one female patients from the Middle East and Africa and 30 from Sweden were recruited. P-25(OH)D was measured and intake of vitamin D was estimated with a modified food frequency questionnaire (FFQ). Results: Vitamin D deficiency (plasma-25(OH)D <25 nmol/L) was common among immigrant women (61%). One immigrant woman and half of the Swedish women had optimal levels (plasma-25(OH)D > 50 nmol/L). There was a positive correlation between the intake of vitamin D from food and plasma-25(OH)D. Only three women, all Swedish, reached the recommended intake of vitamin D from food. The immigrant women had lower intake compared to Swedish women (median: 3.1 vs. 5.1 µg/day). The foods that contributed with most vitamin D were fatty fish, fortified milk and margarine. Immigrant women consumed less fortified milk and margarine but more meat. Irrespective of origin, patients with plasma-25(OH)D <25 nmol/L consumed less margarine but more meat. Conclusion: Vitamin D deficiency was common in the immigrant patients and their intake of vitamin D was lower. This highlights the need to target information about vitamin D to immigrant women in order to decrease the risk for vitamin D deficiency. The FFQ was well adapted to its purpose to estimate intake of vitamin D. [ABSTRACT FROM AUTHOR]

Background. Our aim was to determine the incidence of hip fractures within two years after stroke, to identify associated factors, to evaluate which test instruments that best could identify people at risk, and to describe the circumstances that prevailed when they sustained their hip fractures. Method. A total of 377 persons with first-ever stroke were followed up for a 24-month period. Stroke severity, cognition, and associated medical conditions were registered. The following test instruments were used: National Institutes of Health Stroke Scale, Mini-Mental State Examination, Berg Balance Scale, Timed Up & Go, and Stops Walking When Talking. Result. Sixteen of the persons fractured their hip within the study period, which corresponds to an incidence of 32 hip fractures per 1000 person-years. Persons with fractures more often had impaired vision and cognitive impairment and more had had previous fractures. Of the investigated test instruments, Timed Up & Go was the best test to predict fractures. Conclusion. The incidence of hip fractures in persons with stroke was high in this study. Persons with previous fractures, and visual and cognitive defects are at the greatest risk. Certain test instruments could be used in order to find people at risk, which should be targeted for fall preventive measures. [ABSTRACT FROM AUTHOR]

Background and Purpose: Over past decades, targeted therapies and immunotherapy have improved survival and reduced the morbidity of patients with BRAF-mutated melanoma. However, drug resistance and relapse hinder overall success. Therefore, there is an urgent need for novel compounds with therapeutic efficacy against BRAF-melanoma. This prompted us to investigate the antiproliferative profile of a tachykinin-peptide from the Octopus kaurna, Octpep-1 in melanoma.Experimental Approach: We evaluated the cytotoxicity of Octpep-1 by MTT assay. Mechanistic insights on viability and cellular damage caused by Octpep-1 were gained via flow cytometry and bioenergetics. Structural and pharmacological characterization was conducted by molecular modelling, molecular biology, CRISPR/Cas9 technology, high-throughput mRNA and calcium flux analysis. In vivo efficacy was validated in two independent xerograph animal models (mice and zebrafish).Key Results: Octpep-1 selectively reduced the proliferative capacity of human melanoma BRAFV600E -mutated cells with minimal effects on fibroblasts. In melanoma-treated cells, Octpep-1 increased ROS with unaltered mitochondrial membrane potential and promoted non-mitochondrial and mitochondrial respiration with inefficient ATP coupling. Molecular modelling revealed that the cytotoxicity of Octpep-1 depends upon the α-helix and polyproline conformation in the C-terminal region of the peptide. A truncated form of the C-terminal end of Octpep-1 displayed enhanced potency and efficacy against melanoma. Octpep-1 reduced the progression of tumours in xenograft melanoma mice and zebrafish.Conclusion and Implications: We unravel the intrinsic anti-tumoural properties of a tachykinin peptide. This peptide mediates the selective cytotoxicity in BRAF-mutated melanoma in vitro and prevents tumour progression in vivo, providing a foundation for a therapy against melanoma. [ABSTRACT FROM AUTHOR]