tbuckley/cabot-search huggingface dataset:
Decrease in eccentric hamstring strength in runners in the Tirol Speed Marathon * COMMENTARY
Authors: A Koller, G Sumann, W Schobersberger, H Hoertnagl, C Haid
Journal: British Journal of Sports Medicine (2006)

The local muscular endurance of knee flexors, during eccentric work in particular, is important in preventing or delaying kinematic changes associated with fatigue during treadmill running. This result, however, may not be transferable to overground running.To test the hypothesis that overground running is associated with eccentric hamstring fatigue.Thirteen runners (12 male and one female) performed an isokinetic muscle test three to four days before and 18 hours after a marathon. Both legs were tested. The testing protocol consisted of concentric and eccentric quadriceps and hamstring contractions.There were no significant differences between peak torque before and after the race, except that eccentric peak hamstring torque (both thighs) was reduced.Overground running (running a marathon) is associated with eccentric hamstring fatigue. Eccentric hamstring fatigue may be a potential risk factor for knee and soft tissue injuries during running. Eccentric hamstring training should therefore be introduced as an integral part of the training programme of runners.
The influence of genomics and proteomics on the development of potential vaccines against meningococcal infection
Authors: John E Heckels, Jeannette N Williams
Journal: Genome Medicine (2010)

There is a particular need for an effective vaccine against life-threatening meningitis and septicemia caused by Neisseria meningitidis (meningococcus) serogroup B strains. Vaccine strategies incorporating capsular polysaccharide have proved effective against other meningococcal serogroups, but are not applicable to serogroup B. Attention has therefore focused on the subcapsular outer membrane protein antigens as potential vaccine components. The sequencing of genomes from three serogroups and the availability of the corresponding translated protein databases, combined with the development of sensitive proteomic techniques, have opened up new avenues of meningococcal vaccine research. This has resulted in the identification of potential candidate antigens for incorporation into multicomponent meningococcal vaccines.
National audit of supported discharge programmes for management of acute exacerbations of chronic obstructive pulmonary disease 2008
Authors: Jack A Kastelik, Derek Lowe, Robert A Stone, Rhona J Buckingham, C Michael Roberts
Journal: Thorax (2012)

The 2008 UK national chronic obstructive pulmonary disease (COPD) audit examined the use of supported discharge programmes (SDPs) in clinical practice against British Thoracic Society guidelines. 98% of acute UK trusts participated. SDPs were available in 142 of 239 (59%) units. 1630 of 8971 (18%) patients with COPD were treated within SDPs. Median (IQR) stay in hospital for patients within SDPs and those not accepted for SDPs was 3 (1–6) days and 6 (3–11) days (p&lt;0.001), and mortality within 90 days of admission was 4.3% and 6.7%, respectively. SDPs within the UK are safe and effective and reduce length of hospital stay without adverse effects on mortality.
Neurocutaneous Melanocytosis: Outcome Not Uniformly Fatal
Authors: Yasmin Khakoo, Ashfaq Marghoob
Journal: Journal of Clinical Oncology (2009)

TO THE EDITOR: We were perturbed to read the article by Livingstone et al entitled, “Neurocutaneous Melanosis: A Fatal Disease in Early Childhood.” First, the authors use one patient example to declare that neurocutaneous melanocytosis (NCM) is fatal in early childhood. Clinicians perusing Journal of Clinical Oncology may be led to believe, incorrectly, that the disease is universally fatal. Patients with NCM may have serious neurologic issues, but studies reveal that 5% to 30% of patients with large congenital melanocytic nevi (LCMN) have asymptomatic NCM, with the largest registry—Nevus Outreach Inc—estimating approximately 5%. Studies regarding the conversion from asymptomatic NCM to symptomatic NCM are ongoing and range from 7% in Foster et al to 85% in Kinsler et al. It is important to acknowledge that occasionally the symptoms of NCM may be temporary, while at other times they may be controllable with antiseizure medications, removal of surgically resectable mass lesions, or placement of a ventriculoperitoneal shunt. Although the long-term prognosis for patients with symptomatic disease remains guarded, it is not uncommon to encounter patients living relatively normal lives many years after their symptoms first appeared. We encourage Livingstone et al to attend the biennial Nevus Outreach Conference (www.nevus.org), where children and adults with LCMN and/or patients with NCM with or without symptoms gather to socialize and to educate themselves and others about their condition. Secondly, Livingstone et al state that “MRI [magnetic resonance imaging] scans are highly sensitive in detecting melanotic spots on the brain.” This may be true; however, the sensitivity is dependent, to some extent, on the timing of the MRI scan and the size of the melanin deposits. As mentioned by Becher et al, small melanin deposits may be missed on MRI scans. Furthermore, MRI scans performed before myelination of the brain (ie, 4-6 months of age) provide the highest sensitivity for detecting melanin deposits in the leptomeninges since both myelin and melanotic spots appear white on MRI. In other words, myelin may, on occasion, obscure the ability to visualize melanotic spots. Finally, we strongly encourage a multidisciplinary team approach in managing these patients. The members of this team may include primary care physicians, surgeons, radiologists, psychologists, pathologists, dermatologists, and pediatric neurologists.
Outcomes 1 Year after Thrombus Aspiration for Myocardial Infarction
Authors: Bo Lagerqvist, Ole Fröbert, Göran K. Olivecrona, Thórarinn Gudnason, Michael Maeng, Patrik Alström, Jonas Andersson, Fredrik Calais, Jörg Carlsson, Olov Collste, Matthias Götberg, Peter Hårdhammar, Dan Ioanes, Anders Kallryd, Rickard Linder, Anders Lundin, Jacob Odenstedt, Elmir Omerovic, Verner Puskar, Tim Tödt, Eva Zelleroth, Ollie Östlund, Stefan K. James
Journal: New England Journal of Medicine (2014)

Routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) has not been proved to reduce short-term mortality. We evaluated clinical outcomes at 1 year after thrombus aspiration.We randomly assigned 7244 patients with STEMI to undergo manual thrombus aspiration followed by PCI or to undergo PCI alone, in a registry-based, randomized clinical trial. The primary end point of all-cause mortality at 30 days has been reported previously. Death from any cause at 1 year was a prespecified secondary end point of the trial.No patients were lost to follow-up. Death from any cause occurred in 5.3% of the patients (191 of 3621 patients) in the thrombus-aspiration group, as compared with 5.6% (202 of 3623) in the PCI-only group (hazard ratio, 0.94; 95% confidence interval [CI], 0.78 to 1.15; P=0.57). Rehospitalization for myocardial infarction at 1 year occurred in 2.7% and 2.7% of the patients, respectively (hazard ratio, 0.97; 95% CI, 0.73 to 1.28; P=0.81), and stent thrombosis in 0.7% and 0.9%, respectively (hazard ratio, 0.84; 95% CI, 0.50 to 1.40; P=0.51). The composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis occurred in 8.0% and 8.5% of the patients, respectively (hazard ratio, 0.94; 95% CI, 0.80 to 1.11; P=0.48). The results were consistent across all the major subgroups, including grade of thrombus burden and coronary flow before PCI.Routine thrombus aspiration before PCI in patients with STEMI did not reduce the rate of death from any cause or the composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis at 1 year. (Funded by the Swedish Research Council and others; TASTE ClinicalTrials.gov number, NCT01093404.).
The sex hormone system in carriers of BRCA1/2 mutations: a case-control study
Authors: Martin Widschwendter, Adam N Rosenthal, Sue Philpott, Ivana Rizzuto, Lindsay Fraser, Jane Hayward, Maria P Intermaggio, Christopher K Edlund, Susan J Ramus, Simon A Gayther, Louis Dubeau, Evangelia Ourania Fourkala, Alexey Zaikin, Usha Menon, Ian J Jacobs
Journal: The Lancet Oncology (2013)

Penetrance for breast cancer, ovarian cancer, or both in carriers of BRCA1/BRCA2 mutations is disproportionately high. Sex hormone dysregulation and altered end-organ hormone sensitivity might explain this organ-specific penetrance. We sought to identify differences in hormone regulation between carriers of BRCA1/2 and women who are negative for BRCA1/2 mutations.We assessed endometrial thickness for each menstrual cycle day (as an index of hormone regulation) in 393 scans from 228 women in the UK Familial Ovarian Cancer Screening Study (UK FOCSS) known to carry either mutation and 1573 scans from 754 women known to be negative for the mutations. To quantify differences in endometrial thickness we focused on days 10-14 and days 21-26, and calculated the area under the curve. We then compared serum oestradiol and progesterone titres during these days of the menstrual cycle in the same groups. Follicular and luteal oestradiol and progesterone serum titres were grouped into quartiles and odds ratios were calculated with logistic regression.Follicular phase endometrial thickness of carriers of the mutations adjusted for age and day of the menstrual cycle was higher (odds ratio [OR] 1·11, 95% CI 1·03-1·20; p=0·0063) and luteal phase endometrial thickness lower (0·90, 0·83-0·98; p=0·027) than for women negative for the mutations. Median luteal phase titres of progesterone were 121% higher (p=0·00037) in carriers than in women negative for the mutations, and for oestradiol were 33% higher (p=0·007)-ie, 59% of carriers had concentrations of serum progesterone that would have been in the top quartile of concentrations in the control group (OR 8·0, 95% CI 2·1-52·57; p=0·008).Carriers of BRCA1/BRCA2 mutations are exposed to higher titres of oestradiol and progesterone-known risk-factors for breast cancer. Higher titres of oestradiol in carriers are compatible with this hormone having a role in ovarian carcinogenesis in such women. Our findings could not be explained by differential contraceptive pill use.
Autoimmunity in MFG-E8–deficient mice is associated with altered trafficking and enhanced cross-presentation of apoptotic cell antigens
Authors: YuFeng Peng, Keith B. Elkon
Journal: Journal of Clinical Investigation (2011)

Apoptotic cells must be rapidly cleared, as defects in this process can lead to autoimmunity. Milk fat globule EGF factor 8 (MFG-E8) binds to apoptotic cells and facilitates their removal through interaction with phagocytes. Mice deficient in MFG-E8 develop lupus-like autoimmunity associated with accumulation of apoptotic cells in vivo. Here, we have shown that MFG-E8 controls phagocytic ingestion of cell fragments as well as their intracellular processing into MHC-antigen complexes. Older Mfge8-/- mice spontaneously developed dermatitis associated with CD8+ T cell infiltration and striking activation of effector memory CD8+ T cells. CD8+ T cell responses to both exogenous and endogenous apoptotic cell-associated antigens were enhanced in Mfge8-/- mice. MFG-E8 deficiency accelerated the onset of disease in a mouse model of autoimmune diabetes. Enhanced CD8+ T cell responses were attributed to increased cross-presentation by DCs along with increased detection of antigen-MHCI complexes. Intracellular trafficking analysis revealed that intact apoptotic cells ingested by wild-type DCs rapidly fused with lysosomes, whereas smaller fragments persisted in Mfge8-/- DC endosomal compartments for 24 hours. These observations suggest that MFG-E8 deficiency promotes immune responses to self antigens not only by delaying the clearance of dying cells but also by altering intracellular processing, leading to enhanced self-antigen presentation.
Inhibition of AMPK and Krebs Cycle Gene Expression Drives Metabolic Remodeling of <i>Pten</i>-Deficient Preneoplastic Thyroid Cells
Authors: Valeria G. Antico Arciuch, Marika A. Russo, Kristy S. Kang, Antonio Di Cristofano
Journal: Cancer Research (2013)

Rapidly proliferating and neoplastically transformed cells generate the energy required to support rapid cell division by increasing glycolysis and decreasing flux through the oxidative phosphorylation (OXPHOS) pathway, usually without alterations in mitochondrial function. In contrast, little is known of the metabolic alterations, if any, which occur in cells harboring mutations that prime their neoplastic transformation. To address this question, we used a Pten-deficient mouse model to examine thyroid cells where a mild hyperplasia progresses slowly to follicular thyroid carcinoma. Using this model, we report that constitutive phosphoinositide 3-kinase (PI3K) activation caused by PTEN deficiency in nontransformed thyrocytes results in a global downregulation of Krebs cycle and OXPHOS gene expression, defective mitochondria, reduced respiration, and an enhancement in compensatory glycolysis. We found that this process does not involve any of the pathways classically associated with the Warburg effect. Moreover, this process was independent of proliferation but contributed directly to thyroid hyperplasia. Our findings define a novel metabolic switch to glycolysis driven by PI3K-dependent AMPK inactivation with a consequent repression in the expression of key metabolic transcription regulators.
Simultaneous Pressure, Flow and Diameter of the Vena Cava with Fright and Exercise
Authors: EMILIO TAFUR, WARREN G. GUNTHEROTH, Donald G. Breozeale, George A. McGough
Journal: Circulation Research (1966)

The diameter, distending pressure and flow in the superior vena cava and aortic flow were recorded simultaneously in unanesthetized dogs. Atrial systole produced a regurgitant flow pulse and an increase in pressure and diameter. Ventricular systole produced a sharp decrease in caval diameter and a large increase in flow. A second flow pulse occurred during ventricular diastole. Inspiration accelerated flow in the cava. During exercise, the caval diameter invariably decreased. Venoconstriction, however, could be unequivocally demonstrated in only 26% of the treadmill runs. In 88% of 33 recorded treadmill runs, the flow in the vena cava increased before the heart rate increased which, in turn, preceded the increase in aortic stroke volume. Frightening the animal produced a prompt decrease in caval diameter and distending pressure; this gave way to increased pressure, but without a corresponding increase in diameter. Epinephrine and norepinephrine produced a sustained increase in distending pressure and an initial decrease and a more sustained increase in diameter. Isoproterenol produced tachycardia and a decrease in distending pressure and diameter. Acetylcholine caused an initial bradycardia which was associated with an increase in diameter and pressure in the vena cava followed quickly by prolonged tachycardia which was associated with a decrease in pressure and diameter.
Neurological events after successful carotid stenting
Authors: M.W. Liu, G.S. Roubin, A. Mathur, S.S. Iyer, L.S. Dean, N.A. Al-Mubarak, J. Vitek, C. Gomez, J. Terry, G. Yates, K. Kretzer, D. Alfred
Journal: Journal of the American College of Cardiology (1998)
High-Throughput Drug Sensitivity and Resistance Testing (DSRT) Platform Reveals Novel Candidate Drugs For Advanced Phase BCR-ABL1-Positive Leukemia
Authors: Paavo Pietarinen, Muntasir Mamun Majumder, Disha Malani, Astrid Murumägi, Tea Pemovska, Perttu Koskenvesa, Olli Kallioniemi, Krister Wennerberg, Caroline A. Heckman, Satu Mustjoki, Kimmo Porkka
Journal: Blood (2013)
Précis of<i>After Phrenology: Neural Reuse and the Interactive Brain</i>
Authors: Michael L. Anderson
Journal: Behavioral and Brain Sciences (2015)

Neural reuse is a form of neuroplasticity whereby neural elements originally developed for one purpose are put to multiple uses. A diverse behavioral repertoire is achieved by means of the creation of multiple, nested, and overlapping neural coalitions, in which each neural element is a member of multiple different coalitions and cooperates with a different set of partners at different times. Neural reuse has profound implications for how we think about our continuity with other species, for how we understand the similarities and differences between psychological processes, and for how best to pursue a unified science of the mind. After Phrenology: Neural Reuse and the Interactive Brain (2014; henceforth After Phrenology in this Précis) surveys the terrain and advocates for a series of reforms in psychology and cognitive neuroscience. The book argues that, among other things, we should capture brain function in a multidimensional manner, develop a new, action-oriented vocabulary for psychology, and recognize that higher-order cognitive processes are built from complex configurations of already evolved circuitry.
Nuclear Exclusion of Wild-Type p53 in Immortalized Human Retinoblastoma Cells
Authors: C. L. Schlamp, G. L. Poulsen, T. M. Nork, R. W. Nickells
Journal: JNCI Journal of the National Cancer Institute (1997)

Retinoblastoma is the most common childhood tumor of the eye, arising from cells that are defective in both copies of the retinoblastoma susceptibility gene (RB1). Most retinoblastoma tumor cells eventually undergo programmed cell death (i.e., apoptosis); however, some cells can acquire the ability to metastasize and become immortal. Transfection of immortal retinoblastoma cells with DNA sequences encoding wild-type p53 protein induces cell death, suggesting that the loss of both RB1 and p53 functions may be required for cell immortalization. We have examined this possibility by characterizing the p53 protein and messenger RNA in six independently isolated, immortalized retinoblastoma cell lines.Western blotting methods were used to assess p53 protein level in each cell line, and Cleavase Fragment-Length Polymorphism analysis of complementary DNAs was used to screen for mutations in p53 messenger RNA. Localization of p53 protein in cells of the immortalized lines and in specimens of retinoblastoma tumors was achieved by means of indirect immunofluorescence and immunocytochemistry, respectively.All six immortalized cell lines expressed wild-type p53 messenger RNA and high levels of p53 protein. Although p53 is normally a nuclear protein, the p53 in four of the six cell lines was located predominately in the cytoplasm; in the remaining two cell lines, p53 was localized in both the nucleus and the cytoplasm. Cytoplasmic localization of p53 in retinoblastoma tumor specimens was rare and usually restricted to cells that had invaded adjacent ocular tissues, indicative of the early stages of metastasis.Some immortalized retinoblastoma cells may exhibit p53 dysfunction through nuclear exclusion of wild-type p53 protein.
Optimal hematocrit for oxygenation of canine intestine.
Authors: A P Shepherd, G L Riedel
Journal: Circulation Research (1982)

To determine the direct effects of hematocrit on intestinal oxygen consumption and to determine whether an optimal hematocrit exists for intestinal oxygenation, we perfused isolated canine gut loops at a constant pressure (120 mm Hg) and varied hematocrit from 80% to 10%. As hematocrit fell, blood flow rose while arterial oxygen content fell. The regression of blood flow on hematocrit was linear, whereas the relationship between oxygen uptake and hematocrit was parabolic, showing a maximal oxygen uptake at an hematocrit of 48.7%. To determine whether the optimal hematocrit for intestinal oxygenation could be altered by changes in vasomotor tone, we performed two other series of experiments. Raising perfusion pressure to 180 mm Hg did not significantly alter the optimal hematocrit for oxygen uptake. However, when we increased the oxygen demands of the gut by placing transportable solutes within the intestinal lumen, the optimal hematocrit for oxygen uptake increased markedly. We conclude that the optimal hematocrit for intestinal oxygenation is slightly higher than the normal range, a finding that could possibly be explained by the plasma skimming known to occur in the intestinal mucosa. Our experimental design and method of data analysis could be used to determine the optimal hematocrit in other organs.
Psychiatric Sequelae of Termination of Pregnancy
Authors: M. D. Enoch
Journal: BMJ (1967)

Pressurized Aerosols in Asthma SIR,-We suspect that patients with asthma may be killing themselves by the excessive use of sympathomimetic agents in the form of metered or pressurized aerosols containing isoprenaline, orciprenaline, or adrenaline.We
Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda
Authors: Maria J Wawer, Aaron AR Tobian, Godfrey Kigozi, Xiangrong Kong, Patti E Gravitt, David Serwadda, Fred Nalugoda, Frederick Makumbi, Victor Ssempiija, Nelson Sewankambo, Stephen Watya, Kevin P Eaton, Amy E. Oliver, Michael Z Chen, Steven J Reynolds, Thomas C Quinn, Ronald H Gray
Journal: The Lancet (2011)
Chronic hepatitis B infection in adolescents vaccinated at birth: An alarm bell in favor of the need for a booster?
Authors: Luisa Romanò, Rita Carsetti, Alberto E. Tozzi, Alfonso Mele, Alessandro R. Zanetti
Journal: Hepatology (2013)

Wu et al.1 reported that a significant proportion of adolescents born to hepatitis B surface antigen (HBsAg)-positive mothers, who had postnatal hepatitis B immune globulin (HBIG) and hepatitis B vaccine, lost immune memory and developed a HBsAg carrier state. Having maternal hepatitis B e antigen (HBeAg) positivity was the most important determinant for developing chronic hepatitis B. Vaccination has proved to be highly effective in preventing and controlling hepatitis B, carrier rate, and hepatitis B virus (HBV)-related mortality worldwide. Long-term protection studies indicate that vaccine-induced anti-HBs concentrations decline over time, with antibody (Ab) levels falling below the protective threshold (10 mIU/mL) in one third to one half of vaccinees 10-20 years later; however, immunological memory usually persists.2, 3 This is because Ab maintenance after vaccination depends on the number of long-lived plasma cells, whereas booster response is a function of memory B cells. Evidence indicates that memory B cells effectively respond to antigen challenge even when Ab falls below the protective level.4 Thus, booster doses are not needed in immunocompetent individuals to maintain long-term protection. However, failure to develop postbooster anamnestic response has been reported, raising concern that immune memory may wane during the second decade postvaccination.5, 6 In his study, Wu et al. show that 15% of adolescents born to HBsAg/HBeAg-positive mothers who received primary infantile vaccination developed chronic HBV infection. In addition, one sixth of vaccinees were unable to respond to booster vaccination, having lost immunological memory. Individuals who lost immunological memory may become vulnerable to HBV infection, especially in highly endemic regions—such as some Asiatic countries—where HBsAg carriers are often positive for HBeAg, then highly infectious. Thus, need for a booster in this setting, where risk of acquiring infection and becoming chronic is high, should be considered. If this were the policy, booster should be given before loss of immunological memory occurs. Luisa Romanò, Ph.D.1 Rita Carsetti, M.D.2 Alberto E. Tozzi, M.D.3 Alfonso Mele, M.D.4 Alessandro R. Zanetti, Ph.D.1 1Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milano, Italy 2Immunology Research Area and Immunological Diagnosis Unit, Bambino Gesù Children's Hospital, Rome, Italy 3Research Area of Multifactorial Diseases and Complex Phenotypes, Bambino Gesù Children's Hospital, Rome, Italy 4National Center of Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy