Limited predictive value of achieving beneficial plasma (Z)-endoxifen threshold level by CYP2D6 genotyping in tamoxifen-treated Polish women with breast cancer

Background Tamoxifen, the most frequently used drug for treating estrogen receptor-positive breast cancer, must be converted into active metabolites to exert its therapeutic efficacy, mainly through CYP2D6 enzymes. The objective of this study was to investigate the impact of CYP2D6 polymorphisms on (Z)-endoxifen-directed tamoxifen metabolism and to assess the usefulness of CYP2D6 genotyping for identifying patients who are likely to have insufficient (Z)-endoxifen concentrations to benefit from standard therapy. Methods Blood samples from 279 Polish women with breast cancer receiving tamoxifen 20 mg daily were analyzed for CYP2D6 genotype and drug metabolite concentration. Steady-state plasma levels of tamoxifen and its 14 metabolites were measured by using the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. Results In nearly 60 % of patients, including over 30 % of patients with fully functional CYP2D6, (Z)-endoxifen concentration was below the predefined threshold of therapeutic efficacy. The most frequently observed CYP2D6 genotype was EM/PM (34.8 %), among which 83.5 % of patients had a combination of wild-type and *4 alleles. Plasma concentration of five metabolites was significantly correlated with CYP2D6 genotype. For the first time, we identified an association between decreased (E/Z)-4-OH-N-desmethyl-tamoxifen-β-D-glucuronide levels (r 2  = 0.23; p < 10 −16 ) and increased CYP2D6 functional impairment. The strongest correlation was observed for (Z)-endoxifen, whose concentration was significantly lower in groups of patients carrying at least one CYP2D6 null allele, compared with EM/EM patients. The CYP2D6 genotype accounted for plasma level variability of (Z)-endoxifen by 27 % (p < 10 −16 ) and for the variability of metabolic ratio indicating (Z)-endoxifen-directed metabolism of tamoxifen by 51 % (p < 10 −43 ). Conclusions The majority of breast cancer patients in Poland may not achieve a therapeutic level of (Z)-endoxifen upon receiving a standard dose of tamoxifen. This finding emphasizes the limited value of CYP2D6 genotyping in routine clinical practice for identifying patients who might not benefit from the therapy. In its place, direct monitoring of plasma steady-state (Z)-endoxifen concentration should be performed to personalize and optimize the treatment

Clinical and genetic analysis of 29 Brazilian patients with Huntington’s disease-like phenotype

Huntington’s disease (HD) is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington’s disease-like 2 (HDL2), spinocerebellar ataxia (SCA) 1, SCA2, SCA3, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA) and choreaacanthocytosis (ChAc) among 29 Brazilian patients with a HD-like phenotype. In the group analyzed, we found 3 patients with HDL2 and 2 patients with ChAc. The diagnosis was not reached in 79.3% of the patients. HDL2 was the main cause of the HD-like phenotype in the group analyzed, and is attributable to the African ancestry of this population. However, the etiology of the disease remains undetermined in the majority of the HD negative patients with HD-like phenotype. Key words: Huntington’s disease, Huntington’s disease-like, chorea-acanthocytosis, Huntington’s disease-like 2

The economic impact of moderate stage Alzheimer's disease in Italy: Evidence from the UP-TECH randomized trial

Background: There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families. Methods: This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community. Results: The societal burden of AD, composed of public, patient, and informal care costs, was about �20,000/yr. Out of this, the cost borne by the public sector was �4,534/yr. The main driver of public cost was the national cash-for-care allowance (�2,324/yr), followed by drug prescriptions (�1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at �13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure. Conclusion: The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org (Trial Registration number: NCT01700556). Copyright � International Psychogeriatric Association 2015

Socioeconomic Predictors of the Employment of Migrant Care Workers by Italian Families Assisting Older Alzheimer's Disease Patients: Evidence from the Up-Tech Study

Background: The availability of family caregivers of older people is decreasing in Italy as the number of migrant care workers (MCWs) hired by families increases. There is little evidence on the influence of socioeconomic factors in the employment of MCWs. Method: We analyzed baseline data from 438 older people with moderate Alzheimer's disease (AD), and their family caregivers enrolled in the Up-Tech trial. We used bivariate analysis and multilevel regressions to investigate the association between independent variables - education, social class, and the availability of a care allowance - and three outcomes - employment of a MCW, hours of care provided by the primary family caregiver, and by the family network (primary and other family caregivers). Results: The availability of a care allowance and the educational level were independently associated with employing MCWs. A significant interaction between education and care allowance was found, suggesting that more educated families are more likely to spend the care allowance to hire a MCW. Discussion: Socioeconomic inequalities negatively influenced access both to private care and to care allowance, leading disadvantaged families to directly provide more assistance to AD patients. Care allowance entitlement needs to be reformed in Italy and in countries with similar long-term care and migration systems. � 2015 The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved

Status and Trends of Physical Activity Surveillance, Policy, and Research in 164 Countries: Findings From the Global Observatory for Physical Activity—GoPA! 2015 and 2020 Surveys

Background: Physical activity (PA) surveillance, policy, and research efforts need to be periodically appraised to gain insight into national and global capacities for PA promotion. The aim of this paper was to assess the status and trends in PA surveillance, policy, and research in 164 countries. Methods: We used data from the Global Observatory for Physical Activity (GoPA!) 2015 and 2020 surveys. Comprehensive searches were performed for each country to determine the level of development of their PA surveillance, policy, and research, and the findings were verified by the GoPA! Country Contacts. Trends were analyzed based on the data available for both survey years. Results: The global 5-year progress in all 3 indicators was modest, with most countries either improving or staying at the same level. PA surveillance, policy, and research improved or remained at a high level in 48.1%, 40.6%, and 42.1% of the countries, respectively. PA surveillance, policy, and research scores decreased or remained at a low level in 8.3%, 15.8%, and 28.6% of the countries, respectively. The highest capacity for PA promotion was found in Europe, the lowest in Africa and low- and lower-middle-income countries. Although a large percentage of the world’s population benefit from at least some PA policy, surveillance, and research efforts in their countries, 49.6 million people are without PA surveillance, 629.4 million people are without PA policy, and 108.7 million live in countries without any PA research output. A total of 6.3 billion people or 88.2% of the world’s population live in countries where PA promotion capacity should be significantly improved. Conclusion: Despite PA is essential for health, there are large inequalities between countries and world regions in their capacity to promote PA. Coordinated efforts are needed to reduce the inequalities and improve the global capacity for PA promotion

Basic chemical composition of selected cultivars of oats

Celem badań było określenie zawartości składników odżywczych w pełnym ziarnie, plewce, bielmie i otrębach różnych odmian owsa siewnego. Oceną objęto zawartość: suchej masy, białka, tłuszczu, włókna pokarmowego, węglowodanów ogółem oraz związków mineralnych w postaci popiołu. Podstawowy skład chemiczny materiału badawczego oznaczono metodami standardowymi AOAC. Wyniki otrzymanych badań pozwalają na stwierdzenie, że zarówno pełne ziarno, jak i otręby są dobrym źródłem białka w badanych odmianach owsa. Stwierdzono, że tłuszcz jest równomiernie rozmieszczony w ziarniaku, podobne zawartości tego składnika wykazano zarówno w pełnym ziarnie, bielmie, jak i w otrębach. Najlepszym źródłem węglowodanów i błonnika pokarmowego, a także związków mineralnych jest plewka.The objective of the investigation study was to determine the content of nutrient components in the whole grain, husk, endosperm, and bran in different cultivars of oats. The content of dry mass, protein, fat, dietary fibre, total carbohydrates, and mineral compounds in the form of ash were measured. The basic chemical composition of the research material was determined using the AOAC standard methods. The investigation results received permit to state that both the whole grain and endosperm are a good source of the protein in the oat cultivars investigated. It was also found that the fat was regularly distributed in the caryopsis, and the similar contents of this component were found both in the whole grain, endosperm, and in the bran. The husk is the best source of carbohydrates, dietary fibre, and mineral components

Antioxidant properties of selected cultivars of oats

Celem przeprowadzonych badań była ocena właściwości antyoksydacyjnych pełnego ziarna owsa, plewki, bielma i otrąb. Materiałem badawczym było ziarno owsa siewnego następujących odmian: Akt, Arab, Bohun, Celer, Cwał, Deresz, Flamingsprofi, Furman, Jawor, Kasztan, Krezus, Polar oraz Rajtar. W badanych frakcjach młynarskich oznaczono sumę polifenoli metodą Folina-Ciocalteau’a. Wykonano także oznaczenie zdolności eliminowania wolnego rodnika ABTS•. Największą zawartość polifenoli oznaczono w plewce badanych odmian owsa. Mniejsze ilości stwierdzono odpowiednio w otrębach, pełnym ziarnie i bielmie. Łączy się to w istotny sposób ze zdolnością wygaszania wolnego rodnika ABTS• przez poszczególne frakcje młynarskie badanego materiału.The objective of the investigation study was to assess the antioxidant properties of the whole oat grains, husk, endosperm, and bran. The investigation material was oat grain of the following cultivars: Arab, Bohun, Celer, Cwał, Deresz, Furman, Kasztan, Krezus, Polar, and Rajtar. The content of polyphenol in the milling fractions investigated was measured using a Folin-Ciocalteau method. Additionally, the ability to eliminate an ABTS• free radical was analyzed. The highest polyphenol levels were found in the husk of the oat cultivars investigated. Smaller amounts were found in bran, whole grain, and endosperm, respectively. This is significantly correlated with the radical scavenging activity of individual milling fractions of the material investigated

Anthocyanins – their profile, occurrence, and impact on human organism

Celem niniejszej pracy była chemiczna i biologiczna charakterystyka antocyjanów – barwników szeroko rozpowszechnionych w świecie roślin, o udowodnionych właściwościach prozdrowotnych. Antocyjany należą do polifenolowych związków organicznych – flawonoidów. Obecnie znanych jest kilkaset naturalnych barwników antocyjanowych (uzyskiwanych m.in. z winogron, aronii, czarnych porzeczek) i ponad sto uzyskiwanych syntetycznie. Związki te wykazują właściwości prozdrowotne. Do najważniejszych należy działanie przeciwutleniające, przeciwzapalne, przeciwmiażdżycowe, przeciwnowotworowe.The objective of the paper was to present the chemical and biological profile of anthocyanins - natural dyes, which occur very commonly in the plant world and have proven health benefits. Anthocyanins belong to the polyphenolic organic compounds – flavonoids. At present, there are know several hundred natural anthocyanin pigments (among other things, those isolated from red grapes, chokeberries, and blackcurrants) and more than one hundred synthetic ones. Those compounds show health benefits. Among them, the most important are their antioxidant, anti-inflammatory, anti-atherosclerotic, and anti-carcinogenic activity

Wpływ wydajności krów na wskaźniki rozrodu

Przeanalizowano wpływ wydajności mlecznej na długość okresu międzyciążowego w stadzie krów rasy polskiej holsztyńsko-fryzyjskiej odmiany czarno-białej (phf cb). Przyjęto 3 klasy wydajności mlecznej krów: poniżej 6000 kg mleka z laktacji 305-dniowej, 6000–9000 kg i powyżej 9000 kg mleka. W rozpatrywanym stadzie bydła zaobserwowano tendencję do wydłużania się okresów międzyciążowych w miarę rosnącej wydajności mlecznej krów. Na podstawie analizy wartości indeksu inseminacyjnego, w zależności od wydajności mlecznej krów, najmniejszą wartość tego indeksu (1,23) stwierdzono u krów o wydajności poniżej 6000 kg. Największą wartość indeksu inseminacyjnego (1,47) zanotowano u krów o wydajności mlecznej powyżej 9000 kg.The aim of this study was to analyze the impact of the level of milk productivity on the length of interpregnancy period in a herd of cows of Polish Holstein-Friesian breed black-andwhite breed (phf cb). Three divisions of milk productivity in cows herd has been adopted: less than 6.000 kg per lactation of 305 day, from 6.000–9.000 kg and more than 9.000 kg of milk. In the present herd of cattle it could be concluded that the level of milk productivity of cows affected the length of interpregnancy periods. It was noted that with the increase in milk productivity prolonged interpregnancy periods. Analyzing the value of the index of insemination depending on the level of milk productivity of cows can be observed that the lowest value of the index (1.23) was found in cows with a capacity of less than 6.000 kg. The highest index of insemination value (1.47) was observed in cows with milk productivity above 9.000 kg