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Background: In the United States, >45,000 adolescent and young adult (AYA) women are diagnosed with cancer annually. Reproductive issues are critically important to AYA cancer survivors, but insufficient information is available to address their concerns. The AYA Horizon Study was initiated to contribute high-quality, contemporary evidence on reproductive outcomes for female cancer survivors in the United States. Methods: The study cohort includes women diagnosed with lymphoma, breast, melanoma, thyroid, or gynecologic cancer (the five most common cancers among women ages 15–39 years) at three study sites: the state of North Carolina and the Kaiser Permanente health systems in Northern and Southern California. Detailed information on cancer treatment, fertility procedures, and pregnancy (e.g., miscarriage, live birth) and birth (e.g., birth weight, gestational length) outcomes are leveraged from state cancer registries, health system databases and administrative insurance claims, national data on assisted reproductive technology procedures, vital records, and survey data. Results: We identified a cohort of 11,072 female AYA cancer survivors that includes >1,200 African American women, >1,400 Asian women, >1,600 Medicaid enrollees, and >2,500 Hispanic women using existing data sources. Active response to the survey component was low overall (N ¼ 1,679), and notably lower among minority groups compared with non-Hispanic white women. Conclusions: Passive data collection through linkage reduces participant burden and prevents systematic cohort attrition or potential selection biases that can occur with active participation requirements. Impact: The AYA Horizon study will inform survivorship planning as fertility and parenthood gain increasing recognition as key aspects of high-quality cancer care.

Tumor growth and progression depends on tumor angiogenesis, the growth of tumor blood vessels, therefore, targeting tumor angiogenesis is a very promising approach for controlling tumor growth and/or causing regression. Tumor blood vessels have been recognized as a critical component of radiation response to the point of being independent of tumor oxygenation during radiation. An anti-angiogenic approach has been considered less likely to develop drug resistance. But recent findings suggest that anti-angiogenesis causes hypoxia that selects tumor cells (due to genetic instability) that are less dependent on blood supply and leads to drug resistance. The approach of combination of anti-angiogenesis with ionizing radiation by targeting both endothelial and tumor cells should minimize this possibility. The combination may produce a synergistic anti-tumor effect.

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В руслі авторських концепцій функціонально-метаболічного континууму і нейроендокринно-імунного комплексу з використанням методів дискримінантного і канонічного кореляційного аналізів продемонстровано, що молекула сечової кислоти проявляє відчутну фізіологічну активність і може вважатися четвертою ендогенною сигнальною молекулою поряд з NO, CO і H2S. Для біохіміків, патофізіологів, ендокринологів, імунологів. The monograph highlights the results of priority experimental and clinical-physiological studies of the relationship between uricemia and uricosuria with the parameters of urea, creatinine and electrolyte metabolism and the neuro-endocrine-immune complex. In line with the author's concepts of the functional-metabolic continuum and the neuroendocrine-immune complex using the methods of discriminant and canonical correlation analyses, it was demonstrated that the uric acid molecule exhibits significant physiological activity and can be considered the fourth endogenous signal molecule along with NO, CO and H2S. For biochemists, pathophysiologists, endocrinologists, immunologists. Аннотація В експерименті на здорових щурах виявлено широкий діапазон параметрів обміну сечової кислоти і вперше показано, що з ними значуще корелюють 34 імунні параметри із 41 зареєстрованого. Урикозурія (більшою мірою) і урикемія (меншою мірою), взяті разом, детермінують стан імунітету на 71%. Сечова кислота стимулює фагоцитоз Staph. aureus нейтрофілами (але не моноцитами) крові, збільшує відносний вміст лімфоцитів загалом і В-лімфоцитів зокрема в крові, Т-лімфоцитів і макрофагів в тимусі та фібробластів в селезінці, а також нарощує ентропію імуноцитограми крові. З іншого боку, сечова кислота зменшує ентропію лейкоцитограми крові, загальний вміст в крові лейкоцитів і відносний вміст в лейкоцитограмі моноцитів і паличкоядерних нейтрофілів, натуральних кілерів в імуноцитограмі, а також ентропію тимоцитограми і вміст в ній епітеліоцитів і ретикулоцитів. Вперше показано, що з-поміж нейро-ендокринних факторів адаптації урикозурія і урікемія негативно корелюють з ВРС-маркерами симпатичного тонусу і циркулюючих катехоламінів, рівнем в плазмі кортикостерону і товщиною фасцикулярної зони кори наднирників, а також рівнем в плазмі трийодтироніну і Са-Р-маркером кальцитонінової активності, натомість позитивно корелюють з ВРС-маркером вагального тонусу і екскрецією з сечею 17-кетостероїдів. Міра детермінації сечовою кислотою нейро-ендокринних факторів адаптації становить 62%. Сукупний детермінуючий вплив параметрів обміну сечової кислоти (за значної переваги урикозурії над урикемією) на констеляцію метаболічних параметрів становить 56%. Максимальній позитивній детермінації з боку сечової кислоти підлеглі діурез і екскреція фосфатів та калію, меншою мірою детермінуються екскреція кальцію, креатиніну і сечовини, ще меншою – рівні креатиніну, сечовини і калію в плазмі, а мінімальній детермінації підлегла магнійурія. У людей обох статей, хворих на хронічний пієлонефрит в фазі ремісії, виявлено чотири варіанти обміну сечової кислоти. У 34% помірна гіпоурикозурія поєднується з нижньопограничною урикемією. У 24% помірно підвищена урикозурія асоціюється із нормальною урикемією. У 17% помірно підвищена урикозурія поєднується з вираженою гіпоурикемією. Нарешті, у 25% пацієнтів нижньопогранична урикемія супроводжується вираженою гіперурикозурією. З-поміж усіх зареєстрованих параметрів в якості розпізнавальних щодо чотирьох варіантів обміну сечової кислоти виявлено 28. У дискримінантну модель включено, окрім урикозурії і урикемії за визначенням, 6 нейроендокринних параметрів адаптації (кортизол, трийодтиронін, тестостерон, кальцитонін, вегетативний індекс Кердьо і Са/К-маркер симпато-вагального балансу), 8 параметрів імунітету (активність і завершеність фагоцитозу нейтрофілами грампозитивних і грамнегативних бактерій, рівень в крові загальних лімфоцитів, інтерлейкіну-1β, IgG та IgA в слині), два інформаційні параметри (індекс напруження лейкоцитограми Поповича і ентропія імуноцитограми), 7 параметрів метаболізму електролітів (магній, калій, фосфати) і неелектролітів (глюкоза, сечовина і креатинін), а також маркери хронічного пієлонефриту (бaктерійурія і лейкоцитурія) і мікробіоти (Bifidobacteria). Вперше показано, що динаміка урикозурії позитивно детермінує динаміку діурезу і екскреції сечовини, креатиніну, кальцію, фосфатів, магнію, хлориду і калію та калійемії, рівня Т-гелперів, ВРС-маркерів вагального тонусу і симпато-вагального балансу. Натомість негативній детермінації підлеглі зміни вегетативного індексу Кердьо та інтенсивності фагоцитозу Staph. aureus. Динаміка такої констеляції параметрів організму детермінується динамікою сечової кислоти на 97%. Динаміка урикемії детермінує динаміку вегетативного індексу Кердьо, кортизолу і кальцитоніну негативно, натомість електролітних маркерів паратироїдної активності і симпато-вагального балансу та тестостерону – позитивно. З-поміж імунних параметрів негативній сечокислій детермінації підлеглі зміни Т-гелперів і TNF-α, натомість позитивній – ЦІК, моноцитів і IgG. Стосовно параметрів метаболізму спостерігається лише позитивна сечокисла детермінації їх динаміки. Метаболічна констеляція включає кальційемію, хлоридемію, магнійемію, а також діурез та екскрецію хлориду, натрію, сечовини і креатиніну. В цілому сечокисла детермінація динаміки перелічених параметрів організму становить 80%. Одержані результати розвивають і доповнюють концепцію, що ендогенна сечова кислота володіє фізіологічною активністю, яка проявляється у модуляції параметрів нейроендокринно-імунного комплексу і метаболізму. Gozhenko AI, Korda MM, Smagliy VS, Badiuk NS, Zukow W, Klishch MI, Korda IV, Bombushkar IS, Popovych IL. Uric Acid, Metabolism, Neuro-Endocrine-Immine Complex. Odesa. Feniks; 2023: 266 p. Annotation In an experiment on healthy rats, a wide range of parameters of uric acid metabolism was revealed, and it was shown for the first time that 34 immune parameters out of 41 registered were significantly correlated with them. Uricosuria (to a greater extent) and uricemia (to a lesser extent), taken together, determine the state of immunity by 71%. Uric acid stimulates the phagocytosis of Staph. aureus by neutrophils (but not monocytes) of the blood, increases the relative content of lymphocytes in general and B-lymphocytes in particular in the blood, T-lymphocytes and macrophages in the thymus and fibroblasts in the spleen, and also increases the entropy of the blood immunocytogram. On the other hand, uric acid reduces the entropy of the blood leukocytogram, the total content of leukocytes in the blood and the relative content of monocytes and rod-shaped neutrophils in the leukocytogram, natural killers in the immunocytogram, as well as the entropy of the thymocytogram and the content of epitheliocytes and reticulocytes in it. For the first time, it was shown that among the neuro-endocrine factors of adaptation, uricosuria and uricemia are negatively correlated with HRV-markers of sympathetic tone and circulating catecholamines, the plasma level of corticosterone and the thickness of the fascicular zone of the adrenal cortex, as well as the plasma level of triiodothyronine and the Ca-P marker calcitonin activity, on the other hand, are positively correlated with HRV-marker of vagal tone and urinary excretion of 17-ketosteroids. The rate of determination of neuro-endocrine adaptation factors by uric acid is 62%. The cumulative determining influence of parameters of uric acid metabolism (due to the significant advantage of uricosuria over uricemia) on the constellation of metabolic parameters is 56%. Diuresis and excretion of phosphates and potassium are subject to the maximum positive determination by uric acid, excretion of calcium, creatinine and urea are determined to a lesser extent, levels of creatinine, urea and potassium in plasma are even less determined, and magnesiumuria is subject to the minimum determination. In people of both sexes, patients with chronic pyelonephritis in the phase of remission, four variants of uric acid metabolism were found. In 34%, moderate hypouricosuria is combined with lower borderline uricemia. In 24%, moderately increased uricosuria is associated with normal uricemia. In 17%, moderately increased uricosuria is combined with pronounced hypouricemia. Finally, in 25% of patients, subliminal uricemia is accompanied by marked hyperuricosuria. Among all the registered parameters, 28 were identified as identifying four variants of uric acid metabolism. In addition to uricosuria and uricemia by definition, the discriminant model included 6 neuroendocrine parameters of adaptation (cortisol, triiodothyronine, testosterone, calcitonin, Kerdoe’s autonomic index and Ca/K-marker of sympatho-vagal balance), 8 parameters of immunity (activity and completion of phagocytosis by neutrophils of gram-positive and gram-negative bacteria, the levels of total lymphocytes, interleukin-1β, IgG in the blood and IgA in saliva), two informational parameters (the Popovych’s leukocytogram strain index and the entropy of the immunocytogram), 7 parameters of electrolyte metabolism (magnesium , potassium, phosphates) and non-electrolytes (glucose, urea and creatinine), as well as markers of chronic pyelonephritis (bacteriuria and leukocyturia) and microbiota (Bifidobacteria). It was shown for the first time that the dynamics of uricosuria upregulates the dynamics of diuresis and excretion of urea, creatinine, calcium, phosphates, magnesium, chloride and potassium and plasma potassium, the level of T-helpers, HRV-markers of vagal tone and sympatho-vagal balance. Instead, changes in the Kerdoe’s vegetative index and the intensity of Staph. aureus phagocytosis are subject to downregulation. The dynamics of such a constellation of body parameters is determined by the dynamics of uric acid by 97%. The dynamics of uricemia determines the dynamics of the Kerdoe’s autonomic index, cortisol and calcitonin negatively, instead of the electrolyte markers of parathyroid activity and sympatho-vagal balance and testosterone - positively. Among the immune parameters, changes in T-helpers and TNF-α are subject to negative uric acid determination, while positive ones include CIC, monocytes, and IgG. Regarding metabolic parameters, only positive uric acid determination of their dynamics is observed. The metabolic constellation includes calciumemia, chlorideemia, magnesiumemia, as well as diuresis and excretion of chloride, sodium, urea, and creatinine. In general, uric acid determines the dynamics of the listed parameters of the body by 80%. The obtained results develop and complement the concept that endogenous uric acid has physiological activity, which is manifested in the modulation of the parameters of the neuroendocrine-immune complex and metabolism.

lin p.c., lin l.c., shyu y.i.l. & hua m.s. (2010) Chinese version of the Pain Assessment in Advanced Dementia Scale: initial psychometric evaluation. Journal of Advanced Nursing 66(10), 2360–2368. Abstract Aim. This paper is a report of the validity and reliability testing of the Chinese version of the Pain Assessment in Advanced Dementia Scale (PAINAD-C). Background. Pain is under-reported and under-treated for people with dementia, largely due to impairment of communication. An adequate instrument for assessment of pain in this population is essential to improving their quality of life and decreasing disability and behavioural disturbances, but none were found that were appropriate for these purposes. Method. The PAINAD-C was developed in three phases in 2006. First, back-translation was used to create the Chinese version, where five medical and nursing experts assessed content validity. Inter-rater reliability, internal consistency reliability and test–retest reliability were then examined. Finally, principal component analysis and known-group comparisons were used to test construct validity. Participants with dementia were selected from five licensed long-term care facilities in Taiwan. Direct observation was used to collect data. Results. Inter-rater reliability showed an intra-class correlation coefficient of 0·80–0·86, and a test–retest reliability intra-class correlation coefficient of 0·71. The internal consistency reliability was 0·55–0·66. Factor analysis of the PAINAD-C showed two factors that explained 62·48% of variance. The PAINAD-C scores showed statistically significant differences between the non-dementia group and the advanced dementia group as well as significant differences between activities and rest groups. Conclusion. The PAINAD-C is useful in a clinical setting for people with advanced dementia for both research and practice. It is easy to use and is a comprehensive instrument.

This paper points out a flaw in the derivation of the optimal price and warranty length policies proposed by Wu et al. (2006) (Wu, C.C., Lin, P.C., Chou, C.Y. Determination of price and warranty length for a normal lifetime distributed product. International Journal of Production Economics 102 (2006): 95–107). While we show one of the optimal strategies that they considered is incorrect, correct versions of the optimal strategies are presented.