tbuckley/cabot-search huggingface dataset:
Objectively measured physical activity trajectories predict adolescent bone strength: Iowa Bone Development Study
Authors: Kathleen F Janz, Elena M Letuchy, Trudy L Burns, Julie M Eichenberger Gilmore, James C Torner, Steven M Levy
Journal: British Journal of Sports Medicine (2014)

Background Physical activity improves bone strength and reduces the risk for osteoporotic fractures. However, there are substantial gaps in our knowledge as to when, how and how much activity is optimal for bone health. Purpose In this cohort study, we examined developmental trajectories of objectively measured physical activity from childhood to adolescence to discern if moderate-and-vigorous intensity physical activity (MVPA) predicts bone strength. Methods Starting at age 5 and continuing at 8, 11, 13, 15 and 17 years, Iowa Bone Development Study participants (n=530) wore an accelerometer for 3–5 days. At age 17, we assessed dual X-ray energy absorptiometry outcomes of mass and estimated geometry (femoral neck cross-sectional area and section modulus). We also assessed geometric properties (bone stress index and polar moment of inertia) of the tibia using peripheral computer quantitative tomography. Latent class modelling was used to construct developmental trajectories of MVPA from childhood to late adolescence. General linear models were used to examine the trajectory groups as predictors of age 17 bone outcomes. Results Girls and boys who accumulated the most MVPA had greater bone mass and better geometry at 17 years when compared to less active peers. The proportion of participants achieving high levels of MVPA throughout childhood was very low (&lt;6% in girls) and by late adolescence almost all girls were inactive. Conclusions Bone health benefits of physical activity are not being realised due to low levels of activity for most youth, especially in girls.
American Cancer Society prostate cancer survivorship care guidelines
Authors: Ted A. Skolarus, Andrew M.D. Wolf, Nicole L. Erb, Durado D. Brooks, Brian M. Rivers, Willie Underwood, Andrew L. Salner, Michael J. Zelefsky, Jeanny B. Aragon‐Ching, Susan F. Slovin, Daniela A. Wittmann, Michael A. Hoyt, Victoria J. Sinibaldi, Gerald Chodak, Mandi L. Pratt‐Chapman, Rebecca L. Cowens‐Alvarado
Journal: CA A Cancer Journal for Clinicians (2014)

Abstract Answer questions and earn CME/CNE Prostate cancer survivors approach 2.8 million in number and represent 1 in 5 of all cancer survivors in the United States. While guidelines exist for timely treatment and surveillance for recurrent disease, there is limited availability of guidelines that facilitate the provision of posttreatment clinical follow‐up care to address the myriad of long‐term and late effects that survivors may face. Based on recommendations set forth by a National Cancer Survivorship Resource Center expert panel, the American Cancer Society developed clinical follow‐up care guidelines to facilitate the provision of posttreatment care by primary care clinicians. These guidelines were developed using a combined approach of evidence synthesis and expert consensus. Existing guidelines for health promotion, surveillance, and screening for second primary cancers were referenced when available. To promote comprehensive follow‐up care and optimal health and quality of life for the posttreatment survivor, the guidelines address health promotion, surveillance for prostate cancer recurrence, screening for second primary cancers, long‐term and late effects assessment and management, psychosocial issues, and care coordination among the oncology team, primary care clinicians, and nononcology specialists. A key challenge to the development of these guidelines was the limited availability of published evidence for management of prostate cancer survivors after treatment. Much of the evidence relies on studies with small sample sizes and retrospective analyses of facility‐specific and population databases. CA Cancer J Clin 2014;64:225–249. © 2014 American Cancer Society .
Familial Multiple Myeloma: a Family Study and Review of the Literature
Authors: H. T. Lynch, W. G. Sanger, S. Pirruccello, B. Quinn-Laquer, D. D. Weisenburger
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: The etiology of multiple myeloma (MM) remains obscure, although reports of familial clustering have implicated both a host susceptibility factor and environmental effects. Here we describe the medical histories of members of a family prone to MM. Methods: We developed a pedigree for an MM-prone family by using information obtained from a questionnaire. Protein immunoelectrophoresis of serum and urine from the proband and from 19 family members was performed to detect monoclonal immunoproteins. Peripheral blood obtained from the proband and from five relatives was subjected to standard cytogenetic studies to detect constitutional chromosomal abnormalities. Multifluor-fluorescence in situ hybridization (M-FISH) and standard FISH studies were performed on peripheral blood from the proband and from two other affected living relatives to determine their karyotypes and to detect clonal chromosomal abnormalities frequently seen in patients with MM. Results: Within this family, a sibship of seven included three individuals (including the proband) with histologically verified MM and two individuals with a monoclonal gammopathy of unknown significance (MGUS), as determined by immunoelectrophoresis of serum and urine. This family also had members with acute lymphocytic leukemia, malignant melanoma, and prostate cancer. In the family members tested, we detected no constitutional chromosomal abnormality. None of the three individuals analyzed by FISH had a deletion of the retinoblastoma (Rb-1) locus, which is frequently deleted in patients with MM, and only one (the proband) had a translocation involving chromosomes 11 and 14, a clonal abnormality commonly seen in MM. Conclusion: The study of familial MM may provide insights into the pathogenesis and, ultimately, the control and prevention of MM and related disorders.
Integrin β3 Overexpression Suppresses Tumor Growth in a Human Model of Gliomagenesis
Authors: Masayuki Kanamori, Scott R. Vanden Berg, Gabriele Bergers, Mitchel S. Berger, Russell O. Pieper
Journal: Cancer Research (2004)

Abstract αVβ3 integrin complexes are overexpressed in the growing, invading margins of human glioblastoma multiforme (GBM) and in the GBM vasculature, suggesting a key role for αVβ3 in GBM growth and invasion. The function of αVβ3 complexes in tumor formation, however, has been challenged by studies showing that loss of αVβ3 expression (via loss of β3) in the host vasculature enhances, rather than suppresses, the growth of s.c. implanted carcinomas. To directly address the role of tumor-specific αVβ3 overexpression in glioma formation, we increased αVβ3 expression (via overexpression of a wild-type or constitutively activated β3) in human astrocytes genetically modified to form anaplastic astrocytoma-like tumors (Ras cells) on intracranial injection in rats. Overexpression of β3 selectively increased levels of αVβ3 integrin complexes, but had no effect on anchorage-dependent or -independent growth in vitro. After intracranial injection, however, the Ras + β3 cells formed fewer and smaller tumors than did Ras cells. Similarly, Ras-transformed mouse astrocytes that were derived from control animals formed smaller intracranial tumors than those derived from β3 knockout animals. Although tumors formed by human Ras and Ras + β3 cells were similar in blood vessel density, Ras + β3 tumors had smaller, pericyte-depleted vessels and were significantly more hypoxic, suggesting a β3-mediated vascular defect. The growth-suppressive actions of β3, however, could be overcome by stimulation of pathways (Akt or vascular endothelial growth factor) commonly activated in GBM. These results show that tumor-specific αVβ3 overexpression has growth-suppressive effects in gliomas, but that these deleterious effects are mitigated by alterations common to αVβ3-overexpressing GBM.
Micro- and macro-consequences of ooplasmic injections of early haploid male gametes
Authors: N Sofikitis
Journal: Human Reproduction Update (1998)

This review refers to the evolution of ooplasmic injections of round spermatid nuclei ROSNI) or intact round spermatids ROSI). Conclusions from their preliminary application in the hamster, rabbit, mouse and human are discussed. Criteria for identification of round spermatids and guidelines/quality control for application of ROSNI/ROSI techniques are emphasized. Although all the animal offspring and the human newborns delivered after ROSNI/ROSI are healthy additional research efforts are necessary to confirm the safety of these procedures and improve their outcome
Phase I Study of OSI-7904L, a Novel Liposomal Thymidylate Synthase Inhibitor in Patients with Refractory Solid Tumors
Authors: Gernot Beutel, Hilary Glen, Patrick Schöffski, Jon Chick, Stan Gill, James Cassidy, Chris Twelves
Journal: Clinical Cancer Research (2005)

Abstract Purpose: OSI-7904L is a liposomal formulation of a potent noncompetitive thymidylate synthase inhibitor (TSI) that does not require polyglutamation for activity. This phase I study was done to establish the safety, tolerability, maximum tolerated dose, recommended dose, and pharmacokinetics of OSI-7904L in patients with advanced solid tumors refractory to standard therapy. Design: OSI-7904L was given as a 30-minute i.v. infusion every 21 days to 31 patients at eight dose levels from 0.4 to 15.0 mg/m2, using three patients per dose level, up to 10 patients at the recommended dose. Baseline plasma homocysteine and 2′-deoxyuridine and genotype polymorphism were measured as potential predictors of biological activity. Results: Minimal toxicity was reported up to 9.6 mg/m2, but dose-limiting toxicity was seen in both patients at 15 mg/m2 including stomatitis, fatigue, tachyarrhythmia, rash and hand-foot syndrome, diarrhea, and fatal neutropenic sepsis. Other toxicity such as nausea and vomiting was mild or moderate. This resulted in the investigation of an intermediate dose level of 12 mg/m2, identified as the recommended dose for phase II studies. Prolonged disease stabilization was reported in 11 of 31 heavily pretreated patients. Pharmacokinetic data indicate that this liposomal formulation alters the disposition properties of the parent drug resulting in a prolonged plasma residence time. Conclusions: OSI-7904L given as a 30-minute i.v. infusion every 21 days is feasible and well tolerated at the recommended phase II dose of 12 mg/m2. The main toxicities are rash, pruritis, lethargy, stomatitis, and myelosuppression. Observed toxicities were predictable and characteristic for TSIs.
Where We Live: Health Care in Rural vs Urban America
Authors: Jane van Dis
Journal: JAMA (2002)

THE ELECTORAL MAP OF 2000—WITH ITS COASTAL BLUE EDGES AND POINtillist urban centers set against great swaths of red—told many political and economic stories. Attitudes toward rural life often reveal a complex mixture of affection and disdain, ideas about neighborliness and isolation, simplicity and provincialism. In his recent essay, “One Nation, Slightly Divisible,” David Brooks argues that the differences between rural and urban America may be merely superficial, exemplified in consumer preferences such as Wal-Mart vs Pottery Barn. Although I agree with his assertion that the two locales possess unique “sensibilities,” there are important differences in rural vs urban health care. While 20% of Americans live in rural areas, only 9% of the nation’s physicians practice there. Poverty—a principal health risk factor in any geographic locale—is more prevalent in rural areas and is often related to increased rates of chronic disease and greater numbers of uninsured citizens. Rural residents have fewer physicians and nurses per capita and increased transportation barriers; they visit a physician less often and later in the course of their illness than do urban residents. This issue of MSJAMA explores the question of whether there are two US health care delivery systems, one urban and one rural. Differences between urban and rural health care exist on a continuum defined by many variables. Susan Blumenthal and Jessica Kagen provide an epidemiologic background in which to consider important differences and markers between rural and urban health. Hilda Heady explores some of the monetary inequities embodied in rural vs urban reimbursement policies. Terry Meden and colleagues describe how distance from a tertiary care center may be related to decisions about mastectomy for rural women with stages I and II breast cancer. Although Roe vs Wade made abortion legal in the United States, this right may be moot in many rural settings. Trude Bennett explores some of these barriers to prenatal care, family planning, surgical contraception, and other reproductive health care services in rural areas. To address the chronic geographic maldistribution of physicians, Howard Rabinowitz and Nina Paynter outline the constructs that inform medical students’ decision to become generalists or specialists and correlatively to practice in a rural vs an urban setting. These inequities in rural vs urban health care delivery are based in structural, economic, and cultural differences. Through increased awareness, research, education, and preventive public health measures, congress, and ultimately communities and the health care providers who serve them, may begin to lessen the degrees of difference.
Androgen Receptor Requires JunD as a Coactivator to Switch on an Oxidative Stress Generation Pathway in Prostate Cancer Cells
Authors: Farideh Mehraein-Ghomi, Hirak S. Basu, Dawn R. Church, F. Michael Hoffmann, George Wilding
Journal: Cancer Research (2010)

Relatively high oxidative stress levels in the prostate are postulated to be a major factor for prostate carcinogenesis and prostate cancer (CaP) progression. We focused on elucidating metabolic pathways of oxidative stress generation in CaP cells. Previously, we showed that the transcription factor JunD is essential for androgen-induced reactive oxygen species (ROS) production in androgen-dependent human CaP cells. We also recently showed that androgen induces the first and regulatory enzyme spermidine/spermine N1-acetyltransferase (SSAT) in a polyamine catabolic pathway that produces copious amounts of metabolic ROS. Here, we present coimmunoprecipitation and Gaussia luciferase reconstitution assay data that show that JunD forms a complex with androgen-activated androgen receptor (AR) in situ. Our chromatin immunoprecipitation assay data show that JunD binds directly to a specific SSAT promoter sequence only in androgen-treated LNCaP cells. Using a vector containing a luciferase reporter gene connected to the SSAT promoter and a JunD-silenced LNCaP cell line, we show that JunD is essential for androgen-induced SSAT gene expression. The elucidation of JunD-AR complex inducing SSAT expression leading to polyamine oxidation establishes the mechanistic basis of androgen-induced ROS production in CaP cells and opens up a new prostate-specific target for CaP chemopreventive/chemotherapeutic drug development.
The emerging epidemic of skin cancer
Authors: C.B. KO, S. WALTON, K. KECZKES, H.P.R. BURY, C. NICHOLSON
Journal: British Journal of Dermatology (1994)

Summary A study of the incidence of skin cancer over a 14-year period in the North Humberside area of the U.K. indicates a steady rise in the numbers of the four most common types of skin cancer. A steep increase in the incidence of squamous cell carcinoma of the skin compared with that of internal squamous cell carcinoma was also detected. Our findings emphasize the need for continuing public education about both the dangers of UV radiation and measures to reduce exposure.
John Oldroyd Forfar
Authors: J. C. Forfar
Journal: BMJ (2013)

John Oldroyd Forfar was born in Glasgow, a son of the Manse, as the carnage of the Somme offensive was ending. With boundless energy and zest for life, he packed a great deal into almost a century of living. Although it is usually the prerogative of the older generation to wax lyrical about their offspring, on this special occasion permit me to reverse the roles.

John Forfar graduated in medicine from St Andrews University. In common with so many soldiers returning from the horrors of the second world war, he had some early uncertainties about career path and options but was always one to exploit opportunities. After some forays into infectious disease, paediatrics as a specialty beckoned, and after specialty training and an early consultant appointment in Dundee, he moved to Edinburgh in 1950, where he practised clinical and academic paediatrics and child life and health for some 32 years. As a child, I visited the Western and Eastern General and Leith hospitals on numerous occasions and remember friendly and generous units. Christmas was always a highlight, with great caring across all staff and a great sense of vocation perhaps less obvious in our current technological world. John Forfar obtained his MD with commendation in 1958, initiating a lifelong research interest in neonatology. He moved to the Sick Children’s Hospital in Edinburgh in 1964 on appointment to the Edward Clark Chair of Chair of Child Life and Health, the first of its kind in the UK. In his inaugural lecture, he challenged the status of children’s hospitals and their low priority in healthcare, making an emphatic case for specialisation within paediatrics. He played an active part in the establishment of the neonatal special care unit in the Simpson Memorial Maternity Pavilion of the Royal Infirmary of Edinburgh and the Edinburgh …
Using hospital mortality rates to judge hospital performance: a bad idea that just won't go away
Authors: Richard Lilford, Peter Pronovost
Journal: BMJ (2010)

Twelve patients with small burr hole skull defects after extra-intracranial arterial bypass surgery were studied. The amplitude and frequency of the sensorimotor rhythm were measured 7 days and 1, 2, 4, and 6 months after surgery in follow-up EEGs from the central region. Seven patients showed a frequency decrease (compared with preoperative measurement) on the operated side 7 days and/or 1 month after surgery. There was no case of frequency decrease 6 months after surgery; four patients displayed a late frequency increase. Ipsilateral amplitude enhancement was never found 7 days postoperatively, but after 6 months in nine patients. Such physical factors as burr holes and bone replacement can only partially explain the amplitude enhancement, and cannot explain the frequency decrease. It may be assumed that temporary clamping of the middle cerebral artery and/or reperfusion of an ischaemic area result in a brief deterioration of brain function, as indicated by frequency slowing and delayed amplitude enhancement; related observations were made in patients with cerebrovascular disorders and mild to moderate neurological deficit about 20 days after the onset and correlated with clinical recovery.
EXPERIMENTS ON THE CONVERSION OF TYPHUS STRAINS
Authors: H. Mooser, Gerardo Varela, Hans Pilz
Journal: The Journal of Experimental Medicine (1934)

Two types of strains of typhus virus are observed in Mexico: first the murine type which is obtained from wild rats in nature, from isolated endemic cases, and from cases during short epidemic outbreaks, and second, the epidemic type of strains which is obtained from long standing serious epidemics. Some of these epidemic strains correspond entirely to strains of historic Old World typhus. Other strains which in their experimental behavior are intermediate between these two types of strains were isolated from the same epidemic. A method is described by which these epidemic non-orchitic strains can be converted into murine strains regularly causing scrotal lesion in guinea pigs and a highly fatal disease in rats. The same results were obtained with an Old World strain of epidemic typhus. The method, which consists of daily blood injections into intraperitoneally inoculated rats, is based on the observation that Rickettsia prowazeki multiplies only within cells which come in constant or frequent contact with fresh blood. It is concluded from our experiments that there does not exist any real difference between the virus of historic Old World typhus and the murine New World typhus. Both are considered to be of murine origin. The murine strains represent the original form of the virus of typhus, whereas the epidemic strains are the result of a prolonged propagation in the cycle man-louse-man.
Hair Cycle–Dependent Basal Cell Carcinoma Tumorigenesis in <i>Ptc1neo67/+</i> Mice Exposed to Radiation
Authors: Mariateresa Mancuso, Simona Leonardi, Mirella Tanori, Emanuela Pasquali, Maria Pierdomenico, Simonetta Rebessi, Vincenzo Di Majo, Vincenzo Covelli, Simonetta Pazzaglia, Anna Saran
Journal: Cancer Research (2006)

Abstract We examined the effects of hair cycle phase on basal cell carcinoma (BCC) tumorigenesis induced by radiation in mice lacking one Patched allele (Ptc1neo67/+). Our results show that Ptc1neo67/+ mouse skin irradiated in early anagen is highly susceptible to tumor induction, as a 3.2-fold incidence of visible BCC-like tumors was observed in anagen-irradiated compared with telogen-irradiated mice. Microscopic nodular BCC-like tumors were also enhanced by irradiation during active hair-follicle growth phases. Interestingly, histologic examination of the tumors revealed a qualitative difference in BCC tumorigenesis depending on hair growth phase at the time of exposure. In fact, in addition to typical BCC-like tumors, we observed development of a distinct basal cell tumor subtype characterized by anti–cytokeratin 14 and anti–smooth muscle actin reactivity. These tumors showed relatively short latency and rapid growth and were strictly dependent on age at irradiation, as they occurred only in mice irradiated in early anagen phase. Examination of anatomic and immunohistochemical relationships revealed a close relation of these tumors with the follicular outer root sheath of anagen skin. In contrast, there are strong indications for the derivation of typical, smooth muscle actin–negative BCC-like tumors from cell progenitors of interfollicular epidermis. These results underscore the role of follicular bulge stem cells and their progeny with high self-renewal capacity in the formation of basal cell tumors and contribute to clarify the relationship between target cell and tumor phenotype in BCC tumorigenesis induced by radiation. (Cancer Res 2006; 66(13): 6606-14)