tbuckley/cabot-search huggingface dataset:
TOXINS AND ANTITOXINS--SNAKE VENOMS AND ANTIVENINS
Authors: Th. Madsen, H. Noguchi
Journal: The Journal of Experimental Medicine (1907)

A specific antivenin against crotalus venom can be prepared bv the immunization of goats. A specific antivenin against water moccasin venom can be produced by the immunization of goats with this venom, modified by hydrochloric acid. Immunization with the unmodified venom is very difficult. The toxicity of crotalus venom is diminished more than fifty percent. by passage through a Chamberland filter. There is a simple relation between the toxicity and the body weight for guinea-pigs weighing from 250 to 500 grams. Smaller guinea-pigs (125 grams) are comparatively less resistant. The toxicity is smaller by subcutaneous than by intraperitoneal injection (guinea-pigs), or by intravenous injection (rabbits). White rats are very resistant. The toxicity of cobra venom is not measurably diminished by filtration through a Chamberland filter. The relation between the amount of venom and the corresponding time of death is very regular, and can be expressed by a curve of asymptotic nature. Lecithin does not increase the toxicity. The tracings representing toxin-antitoxin neutralization for the three venoms (crotalus, cobra and moccasin) show deviation from the straight line. This deviation is most pronounced for the toxic quota of the venoms. The tracing representing crotalus venomantivenin neutralization, determined on guinea-pigs, can, within errors of experiment, be expressed by the equation: Free toxin . Free antitoxin = K . toxin-antitoxin. The corresponding tracing determined on rabbits is somewhat different, but both tracings are much more markedly curved than that for cobra venom-antivenin. The neutralization tracing of water moccasin venom shows the peculiarity, that small amounts of antivenin decrease the toxicity to a minimum, but the toxicity is again increased by further addition of antitoxin. The tracing representing neutralization of the haemolysins of the three venoms are different from the tracings of neutralization of the toxins, and approach very closely to a straight line. Still, in all instances, the determinations with great concentrations of antilysin show pronounced deviation, perhaps due to some dissociation of the toxin-antitoxin combination.
Moderate Hypothermia to Treat Perinatal Asphyxial Encephalopathy
Authors: Denis V. Azzopardi, Brenda Strohm, A. David Edwards, Leigh Dyet, Henry L. Halliday, Edmund Juszczak, Olga Kapellou, Malcolm Levene, Neil Marlow, Emma Porter, Marianne Thoresen, Andrew Whitelaw, Peter Brocklehurst
Journal: New England Journal of Medicine (2009)

Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain.We performed a randomized trial of infants who were less than 6 hours of age and had a gestational age of at least 36 weeks and perinatal asphyxial encephalopathy. We compared intensive care plus cooling of the body to 33.5 degrees C for 72 hours and intensive care alone. The primary outcome was death or severe disability at 18 months of age. Prespecified secondary outcomes included 12 neurologic outcomes and 14 other adverse outcomes.Of 325 infants enrolled, 163 underwent intensive care with cooling, and 162 underwent intensive care alone. In the cooled group, 42 infants died and 32 survived but had severe neurodevelopmental disability, whereas in the noncooled group, 44 infants died and 42 had severe disability (relative risk for either outcome, 0.86; 95% confidence interval [CI], 0.68 to 1.07; P=0.17). Infants in the cooled group had an increased rate of survival without neurologic abnormality (relative risk, 1.57; 95% CI, 1.16 to 2.12; P=0.003). Among survivors, cooling resulted in reduced risks of cerebral palsy (relative risk, 0.67; 95% CI, 0.47 to 0.96; P=0.03) and improved scores on the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development II (P=0.03 for each) and the Gross Motor Function Classification System (P=0.01). Improvements in other neurologic outcomes in the cooled group were not significant. Adverse events were mostly minor and not associated with cooling.Induction of moderate hypothermia for 72 hours in infants who had perinatal asphyxia did not significantly reduce the combined rate of death or severe disability but resulted in improved neurologic outcomes in survivors. (Current Controlled Trials number, ISRCTN89547571.)
Bronchial carcinoma in a young Negro
Authors: P. H. Kidner, H. O. Williams
Journal: Thorax (1969)

A case of bronchial carcinoma occurring in a young Negro is described. The incidence of the condition in the Negro race is reviewed. Although it is apparently rare in the native African, it is much more common in the American of Negro stock. Two factors are suggested as being responsible for this—increasing longevity and increasing contact with external carcinogens, of which the most likely is cigarette smoke. Available evidence indicates that the disease is, as yet, rare in the British Negro but may be expected to rise following the pattern in the United States.
Determinism, omniscience, and the multiplicity of explanations
Authors: Mary Midgley
Journal: Behavioral and Brain Sciences (1999)

Complete determinism is, as Karl Popper said, “a daydream of omniscience.” Determinism is usually conceived as linked with a particular science whose explanations are deemed fundamental. As Rose rightly points out, biological enquiry includes many different kinds of question. Genetic determinism, making genes central to biology, is therefore biased and misguided. The crucial unit must be the whole organism.
Screening Drug-Induced Arrhythmia Using Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes and Low-Impedance Microelectrode Arrays
Authors: Enrique G. Navarrete, Ping Liang, Feng Lan, Verónica Sanchez-Freire, Chelsey Simmons, Tingyu Gong, Arun Sharma, Paul W. Burridge, Bhagat Patlolla, Andrew S. Lee, Haodi Wu, Ramin E. Beygui, Sean M. Wu, Robert C. Robbins, Donald M. Bers, Joseph C. Wu
Journal: Circulation (2013)

Background— Drug-induced arrhythmia is one of the most common causes of drug development failure and withdrawal from market. This study tested whether human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) combined with a low-impedance microelectrode array (MEA) system could improve on industry-standard preclinical cardiotoxicity screening methods, identify the effects of well-characterized drugs, and elucidate underlying risk factors for drug-induced arrhythmia. hiPSC-CMs may be advantageous over immortalized cell lines because they possess similar functional characteristics as primary human cardiomyocytes and can be generated in unlimited quantities. Methods and Results— Pharmacological responses of beating embryoid bodies exposed to a comprehensive panel of drugs at 65 to 95 days postinduction were determined. Responses of hiPSC-CMs to drugs were qualitatively and quantitatively consistent with the reported drug effects in literature. Torsadogenic hERG blockers, such as sotalol and quinidine, produced statistically and physiologically significant effects, consistent with patch-clamp studies, on human embryonic stem cell–derived cardiomyocytes hESC-CMs. False-negative and false-positive hERG blockers were identified accurately. Consistent with published studies using animal models, early afterdepolarizations and ectopic beats were observed in 33% and 40% of embryoid bodies treated with sotalol and quinidine, respectively, compared with negligible early afterdepolarizations and ectopic beats in untreated controls. Conclusions— We found that drug-induced arrhythmias can be recapitulated in hiPSC-CMs and documented with low impedance MEA. Our data indicate that the MEA/hiPSC-CM assay is a sensitive, robust, and efficient platform for testing drug effectiveness and for arrhythmia screening. This system may hold great potential for reducing drug development costs and may provide significant advantages over current industry standard assays that use immortalized cell lines or animal models.
Quantifying β-Cells in Health and Disease: The Past, the Present, and the Need
Authors: Steven E. Kahn
Journal: Diabetes Care (2012)

Through the studies of a number of pathologists, the past has taught us a great deal about islet pathology. A reduction in the quantity of β-cells in hyperglycemic individuals was described over 110 years ago by Eugene Opie (1) in an elegant report that included hand-drawn color micrographs. These illustrations clearly bring attention to the fact that the islet has lost numerous cells and that it also contains hyaline deposits, which we now recognize may be part of the destructive process. The past also included quantification of the number of endocrine cells by MacLean and Ogilvie (2) who demonstrated that β-cell mass is decreased in patients with phenotypic type 2 diabetes, but that the mass of α-cells is not diminished. And then, over 50 years ago, Bell (3) published a report of his studies of hyalinosis in islets that were based on the examination of pancreas sections from 3,959 individuals who were not known to have diabetes and 1,661 with diabetes. He observed hyaline to be more frequent in individuals with diabetes and that the number of affected individuals increased with age. While diabetes was certainly not the epidemic we now face, Bell stated in his commentary that “Hyaline islets are an expression of unrecognized or potential diabetes”—a clear recognition of the link of these deposits to diabetes and the problem of undiagnosed diabetes.

The present includes the study by Saisho et al. (4), which appears in this issue of Diabetes Care . This article builds on the past and the present. The authors describe their findings in pancreas samples obtained at …
Indomethacin Enhances Shuttling of Aquaporin-2 Despite Decreased Abundance in Rat Kidney
Authors: Soo Wan Kim, Joon Wan Kim, Ki Chul Choi, Seong Kwon, YoonWha Oh, Ju-Young Jung, Jin Kim, JongUn Lee
Journal: Journal of the American Society of Nephrology (2004)

The effect of nonsteroidal antiinflammatory drugs on the regulation of aquaporin-2 (AQP2) water channels in the kidney was determined. Male Sprague-Dawley rats were injected with indomethacin (5 mg/kg twice a day intraperitoneally) for 2 d. The control group was injected with vehicle. The expression of AQP2 proteins was determined in the kidney by immunoblotting and immunohistochemistry. The expression of Gsα and type VI adenylyl cyclase was determined by immunoblotting. The activity of adenylyl cyclase complexes was determined by stimulated accumulation of cAMP. Immunoblotting revealed that indomethacin markedly decreased the expression of AQP2. Accordingly, however, the ratio of AQP2 expression in the membrane fraction versus that in the cytoplasmic fraction was increased. The urinary excretion of AQP2 proteins also increased. Immunohistochemistry demonstrated almost exclusive apical labeling of AQP2 with scanty cytoplasmic localization along the collecting duct. The expression of Gsα and adenylyl cyclase VI proteins was decreased. The generation of cAMP provoked by arginine vasopressin, sodium fluoride, or forskolin was blunted. These results suggest that indomethacin increases the shuttling of AQP2 while it decreases its abundance in the collecting duct.
WHAT CAUSES WHOOPING-COUGH ?
Authors: MargaretA Calder, J.H Lawson, J.P Duguid, T.F Elias-Jones, R.J Fallon, R.R Gillies, D.M Green, N.R Grist, W.C Love, P Mckenzie, I.W Pinkerton, ConstanceA.C Ross, G Sangster, A.M.M Wilson
Journal: The Lancet (1970)
Enhanced Intracellular siRNA Delivery using Bioreducible Lipid‐Like Nanoparticles
Authors: Ming Wang, Kyle Alberti, Antonio Varone, Dimitria Pouli, Irene Georgakoudi, Qiaobing Xu
Journal: Advanced Healthcare Materials (2014)

A new library of lipid-like nanoparticles (lipidoids) comprising disulfide bond is developed for siRNA delivery. Bioreducible lipidoids deliver siRNA with greater efficiency than nonbioreducible lipidoids with similar chemical structures. A siRNA release investigation, as well as an intracellular siRNA trafficking study, reveals that the degradation of bioreducible lipidoid in a strongly reductive intracellular environment boosts siRNA release and enhances siRNA gene knockdown efficiency. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Epidemiology of National Collegiate Athletic Association men's and women's swimming and diving injuries from 2009/2010 to 2013/2014
Authors: Zachary Y Kerr, Christine M Baugh, Elizabeth E Hibberd, Erin M Snook, Ross Hayden, Thomas P Dompier
Journal: British Journal of Sports Medicine (2015)

Recent injury data for collegiate-level swimming and diving are limited. This study describes the epidemiology of men's and women's swimming and diving injuries reported by the National Collegiate Athletic Association (NCAA) Injury Surveillance Program (ISP) during the 2009/2010 to 2013/2014 academic years.Injuries and athlete-exposure (AE) data reported within 9 men's and 13 women's swimming and diving programmes were analysed. Injury rates, injury rate ratios (IRR), and injury proportions by body site, diagnosis and mechanism were reported with 95% CIs.The ISP captured 149 and 208 injuries for men's and women's swimming and diving, respectively, leading to injury rates of 1.54/1000 and 1.71/1000 AEs. Among females, divers had a higher injury rate (2.49/1000 AEs) than swimmers (1.63/1000 AEs; IRR=1.53; 95% CI 1.07 to 2.19). Injury rates for male divers (1.94/1000 AEs) and swimmers (1.48/1000 AEs) did not differ (IRR=1.33; 95% CI 0.85 to 2.31). Most injuries occurred to the shoulder, resulted in strains and were classified as overuse or non-contact. Female swimmers had a higher overuse injury rate (1.04/1000 AEs) than male swimmers (0.66/1000 AEs; IRR=1.58; 95% CI 1.14 to 2.19). Overuse injury rates for female divers (0.54/1000 AEs) and male divers (0.46/1000 AEs) did not differ (IRR=1.16; 95% CI 0.40 to 3.34). Injury rates in 2012/2013-2013/2014 were lower than those in 2009/2010-2011/2012 for women's swimming (IRR=0.70; 95% CI 0.52 to 0.95) and diving (IRR=0.56; 95% CI 0.30 to 1.08), respectively. No time trends existed for men's swimmers or divers.Shoulder, strain and overuse injuries were common in collegiate men's and women's swimming and diving. Female swimmers were more likely to suffer an overuse injury than male swimmers. In addition, divers may have higher injury rates than swimmers, although small reported numbers warrant additional research.
Incidence of Lower-Limb Amputation in the Diabetic and Nondiabetic General Population
Authors: Anton Johannesson, Gert-Uno Larsson, Nerrolyn Ramstrand, Aleksandra Turkiewicz, Ann-Britt Wiréhn, Isam Atroshi
Journal: Diabetes Care (2008)

The purpose of this study was to compare the incidence of vascular lower-limb amputation (LLA) in the diabetic and nondiabetic general population.A population-based cohort study was conducted in a representative Swedish region. All vascular LLAs (at or proximal to the transmetatarsal level) performed from 1997 through 2006 were consecutively registered and classified into initial unilateral amputation, contralateral amputation, or reamputation. The incidence rates were estimated in the diabetic and nondiabetic general population aged > or =45 years.During the 10-year period, LLA was performed on 62 women and 71 men with diabetes and on 79 women and 78 men without diabetes. The incidence of initial unilateral amputation per 100,000 person-years was 192 (95% CI 145-241) for diabetic women, 197 (152-244) for diabetic men, 22 (17-26) for nondiabetic women, and 24 (19-29) for nondiabetic men. The incidence increased from the age of 75 years. Of all amputations, 74% were transtibial. The incidences of contralateral amputation and of reamputation per 100 amputee-years in diabetic women amputees were 15 (7-27) and 16 (8-28), respectively; in diabetic men amputees 18 (10-29) and 21 (12-32); in nondiabetic women amputees 14 (7-24) and 18 (10-28); and in nondiabetic men amputees 13 (6-22) and 24 (15-35).In the general population aged > or =45 years, the incidence of vascular LLA at or proximal to the transmetatarsal level is eight times higher in diabetic than in nondiabetic individuals. One in four amputees may require contralateral amputation and/or reamputation.
Progressive replacement of embryo-derived cardiac macrophages with age
Authors: Kaaweh Molawi, Yochai Wolf, Prashanth K. Kandalla, Jeremy Favret, Nora Hagemeyer, Kathrin Frenzel, Alexander R. Pinto, Kay Klapproth, Sandrine Henri, Bernard Malissen, Hans-Reimer Rodewald, Nadia A. Rosenthal, Marc Bajenoff, Marco Prinz, Steffen Jung, Michael H. Sieweke
Journal: The Journal of Experimental Medicine (2014)

Cardiac macrophages (cMΦ) are critical for early postnatal heart regeneration and fibrotic repair in the adult heart, but their origins and cellular dynamics during postnatal development have not been well characterized. Tissue macrophages can be derived from embryonic progenitors or from monocytes during inflammation. We report that within the first weeks after birth, the embryo-derived population of resident CX3CR1+ cMΦ diversifies into MHCII+ and MHCII− cells. Genetic fate mapping demonstrated that cMΦ derived from CX3CR1+ embryonic progenitors persisted into adulthood but the initially high contribution to resident cMΦ declined after birth. Consistent with this, the early significant proliferation rate of resident cMΦ decreased with age upon diversification into subpopulations. Bone marrow (BM) reconstitution experiments showed monocyte-dependent quantitative replacement of all cMΦ populations. Furthermore, parabiotic mice and BM chimeras of nonirradiated recipient mice revealed a slow but significant donor contribution to cMΦ. Together, our observations indicate that in the heart, embryo-derived cMΦ show declining self-renewal with age and are progressively substituted by monocyte-derived macrophages, even in the absence of inflammation.
Postnatal DNA synthesis in hearts of mice: autoradiographic and cytofluorometric investigations
Authors: M. NAKAGAWA, K. HAMAOKA, T. HATTORI, T. SAWADA
Journal: Cardiovascular Research (1988)

Proliferative activity of cardiomyocytes in ICR mice aged from 1 to 200 days old was studied by 3H-thymidine autoradiography. To determine the outcome of cardiomyocytic DNA synthesis, the DNA content of the cardiomyocytic nuclei in different age groups was also examined by a cytofluorometric method. Flash labelling experiments with 3H-thymidine showed that the cardiomyocytes synthesised DNA most actively in the first 14 days after birth; the label was equally distributed in various parts of the heart and seen in about 8.8% of the cardiomyocytic nuclei on the tenth day. Cumulative labelling experiments for seven and 14 days showed that about 90% of the cardiomyocytic nuclei became labelled, indicating that most cardiomyocytic nuclei of young growing mice developed in this period. Twenty days after birth DNA synthesis of the cardiomyocytes rapidly decreased, the label being evident in less than 0.2%. From 100 to 200 days DNA synthesising cardiomyocytes were seen occasionally in the subendocardial region of the left ventricle (labelling index 0.04%). The cytofluorometric study showed that under normal conditions cardiomyocytes in mice contained mostly diploid nuclei, with a few double diploid nuclei considered to be premitotic nuclei. DNA synthesised cardiomyocytes in adult mice hearts usually became binucleated cells.
Number of confirmed A/H1N1 flu cases doubles over one weekend
Authors: A. O'Dowd
Journal: BMJ (2009)

The number of confirmed swine flu cases worldwide rose by 88% over the weekend of 9 and 10 May, from 2500 to 5251, in 30 countries, the World Health Organization has said.

As the number of cases of A/H1N1 flu rose, the first death linked to it in Canada was announced. A woman from northern Alberta who had chronic pre-existing health problems and who had not travelled to Mexico died on 28 April.

The numbers of deaths had risen to 48 in Mexico, three in the United States, one in Canada, and one in Costa Rica.

The total number of cases in the United Kingdom rose from 39 on Friday 8 May to 65 by the time the BMJ went to press on Tuesday, and laboratory testing is under way in another 336 cases, the Health Protection Agency said.

One of the sharpest rise in cases in the past few days was in the US, which is now the most affected country in the world. It recorded a rise of around …
Moving Toward Economically Sustainable Value-Based Cancer Care in the Academic Setting
Authors: Joseph Alvarnas, Guy R. Majkowski, Alexandra M. Levine
Journal: JAMA Oncology (2015)

Academic cancer centers play a vital role in cancer care in an increasingly cost-sensitive health care market, and proponents must emphasize the value-based clinical, research, and business contributions these centers can make to the eradication of cancer.
Sniff Nasal Inspiratory Pressure
Authors: DANIELA STEFANUT TI, JEAN-WILLIAM FIT TING
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Like in adults, normal values of maximal inspiratory pressure (Pi max) and maximal expiratory pressure (Pe max) span a large range in children, making interpretation of low values difficult. Recently, sniff nasal inspiratory pressure (Pnsn) was developed as a new noninvasive test of inspiratory muscle strength. In healthy adults, Pnsn is most often higher than Pi max. The aim of this study was to establish reference values of Pnsn in children and to compare them with Pi max. A group of 180 unselected healthy children age 6 to 17 yr was studied in a school setting. All had a forced vital capacity (FVC) > 80% of predicted and a ratio of forced expiratory volume in one second/forced vital capacity (FEV1/ FVC) > 85% of predicted. All maneuvers were performed in the sitting position. The Pnsn was measured using a catheter occluding one nostril during maximal sniffs performed through the contralateral nostril from FRC. The Pi max was measured from FRC and residual volume, and Pe max from FRC and total lung capacity. All children were able to perform the Pnsn maneuver easily. Pnsn was 104 ± 26 cm H2O in boys and 93 ± 23 cm H2O in girls (p < 0.005). These values were similar to those previously measured in healthy adults. Pnsn correlated with age, weight, and height in boys, but not in girls. In both sexes, Pnsn was higher than Pi max measured at the same lung volume (FRC) (p < 0.0001). Pnsn was ⩾ Pi maxFRC in 73 of 93 boys and 79 of 87 girls. We conclude that Pnsn can be easily used to assess inspiratory muscle strength in children age 6 yr or more, providing values higher than Pi max. Normal values are independent of age in girls, and can be predicted from age by a first-degree equation in boys. Being easy and noninvasive, Pnsn may prove useful to assess inspiratory muscle strength in children with neuromuscular disorders.