tbuckley/cabot-search huggingface dataset:
Metabolic Signatures of Adiposity in Young Adults: Mendelian Randomization Analysis and Effects of Weight Change
Authors: Peter Würtz, Qin Wang, Antti J. Kangas, Rebecca C. Richmond, Joni Skarp, Mika Tiainen, Tuulia Tynkkynen, Pasi Soininen, Aki S. Havulinna, Marika Kaakinen, Jorma S. Viikari, Markku J. Savolainen, Mika Kähönen, Terho Lehtimäki, Satu Männistö, Stefan Blankenberg, Tanja Zeller, Jaana Laitinen, Anneli Pouta, Pekka Mäntyselkä, Mauno Vanhala, Paul Elliott, Kirsi H. Pietiläinen, Samuli Ripatti, Veikko Salomaa, Olli T. Raitakari, Marjo-Riitta Järvelin, George Davey Smith, Mika Ala-Korpela
Journal: PLoS Medicine (2014)

Background Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood. Methods and Findings We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16–39 y; 51% women; mean ± standard deviation BMI 24±4 kg/m2). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p<0.0005 for 68 measures). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%–183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87%±3%; R2 = 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p<0.0005 for 24 measures), including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation-related glycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power. Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the cross-sectional observations, yet with greater metabolic effects (correspondence 160%±2%; R2 = 0.92). Conclusions Mendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors' Summary
A STUDY OF ONE THOUSAND PSYCHOTIC VETERANS TREATED WITH INSULIN AND ELECTRIC SHOCK
Authors: SAMUEL PASTER, SAUL C. HOLTZMAN
Journal: American Journal of Psychiatry (1949)

l. One thousand psychotic veterans were given electric shock therapy, insulin shock therapy, or a combination of the two in sequence following a period of observation during which they had revealed no tendency toward spontaneous improvement. 2. The large percentage of social recoveries obtained in this group testifies amply to the efficacy of the shock therapies in the treatment of functional psychotic reactions incurred in wartime. 3. The therapeutic superiority of insulin shock is revealed in the greater number of social recoveries obtained both when it is used alone and following unsuccessful treatment with electric shock. Insulin is definitely more effective than electric shock in the treatment of paranoid and catatonic schizophrenia. The remissions attained from insulin treatment are more lasting. 4. Psychotic reactions precipitated under the stress of combat which had not improved spontaneously responded somewhat better to shock therapy than those patients whose psychotic reactions were precipitated under noncombat, environmental stress. 5. The well-integrated prepsychotic personality proved to be of favorable prognostic significance. 6. The more favorable rate of recoveries reported in this study may be related to the fact that the veterans constituted a selected group of young men in whom the psychotic reactions were precipitated under great emotional stress.
Sporotrichosis Presenting as Facial Cellulitis
Authors: Margot C. Pepper
Journal: JAMA (1980)

SPOROTRICHOSIS is an uncommon skin infection frequently involving the lymphatic system and is caused by the fungus<i>Sporothrix schenckii</i>. This organism is ubiquitous, being found in soil and on vegetation.<sup>1</sup>In the Midwest it is an occupational hazard for farmers and horticultural workers. The incidence of sporotrichosis in urban communities is much rarer, and consequently the diagnosis may be delayed.<sup>2</sup>For infection to occur, the organism had to be introduced into the dermis by traumatic implantation. The primary site is most often on an extremity. A rare primary pulmonary form has been reported occurring secondary to inhalation of spores.<sup>3</sup>Subclinical infection may occur in endemic areas. <h3>Report of a Case</h3> A 23-year-old man in good health was initially seen with a small soft-tissue facial infection. On examination a 1-cm, firm, slightly tender lesion was observed. He was afebrile, and no other abnormality was detected. Screening tests for systemic
Contractile activity of bile canaliculi: Contraction or collapse?
Authors: James L. Boyer
Journal: Hepatology (1987)

The discovery that bile canaliculi are capable of spontaneous contractile activity has led to their use in the investigation of the physiology of the liver cell. The contraction of a bile canaliculus is dependent on the network of actin, which is found in the pericanalicular region of the hepatocyte, and agents that inhibit actin filaments interfere with canalicular contraction. Injection of calcium directly into the cytoplasm of one hepatocyte of a cell pair results in contraction of the canaliculus. To determine whether the contractile activity of adjacent bile canaliculi was coordinated, calcium was injected into one cell of a group of three hepatocytes that formed two neighboring bile canaliculi. Calcium microinjection resulted in contraction of the bile canaliculus contiguous with the microinjected cell and was followed by a contraction of the second, adjacent canaliculus. These secondary contractions occurred after an interval of approximately 45 seconds. The finding that bile canalicular contractions are coordinated with contractions occurring in a sequential fashion supports the hypothesis that within the liver lobule, transport of bile within the canalicular network results from the coordinated contractions of the canaliculi. Rat hepatocytes, when isolated and maintained in primary culture, are capable of producing forceful contractions of their bile canaliculi, with contractions occurring on a regular basis once every 5.5 minutes. To determine whether the contraction of one bile canaliculus affected the contraction of a neighboring canaliculus, cinephotomicrographic studies of pairs of contiguous canaliculi were undertaken. The activity of 10 pairs of contiguous canaliculi, and 10 pairs of noncontiguous canaliculi which served as a control group, was recorded for a period of 12.5 hours at the rate of 1 frame every 15 seconds. Using frame-by-frame analysis of this period of observation, we determined the time of contraction of each of the canaliculi in the pairs. Cross-correlations were obtained for the contraction times of each of the 10 pairs of contiguous canaliculi and 10 control pairs. A peak in activity was found, with that peak occurring five frames 75 seconds from the midline, whereas the noncontiguous controls showed no correlation in contractile activity. This finding indicates that, when one bile canaliculus contracts, a neighboring canaliculus is likely to contract after an interval of 1.25 minutes. That there is coordination of contractile activity of bile canaliculi suggests that, within the intact liver lobule, ordered motility function of the bile canaliculi may facilitate bile flow.
Management of testicular torsion
Authors: I. Shergill, M. Arya
Journal: Journal of the Royal Society of Medicine (2002)

Mr Pearce and his colleagues (May 2002 JRSM1) propose a protocol for management of suspected testicular torsion, based on their observations of clinical practice in the North West of England. They recommend fixation with delayed-absorption or non-absorbable sutures. There is, however, much controversy surrounding the method used for testicular fixation when a torted testis is deemed salvageable. Sutureless dartos muscle pouch fixation is a technique which is now increasingly being used by urologists and paediatric surgeons2. The main reason for this is that fixation with sutures, which traverse the blood—testis barrier, can generate an autoimmune response that leads to eventual infertility3. Suture fixation has additional complications. Non-absorbable sutures are associated with the formation of microabscesses and granulomas, predisposing to chronic testicular pain4, whilst absorbable sutures result in only fine adhesions at the site of placement and thus increase the risk of recurrent torsion5. Is suture fixation actually necessary? Eversion of the tunica vaginalis, as is performed in a Jaboulay procedure for hydrocele, leads to the formation of satisfactory adhesions and aids in the prevention of future torsion6. In conclusion, eversion of the tunica vaginalis together with sutureless fixation in a dartos pouch probably provides the best method of fixation.
Investigation of Abnormal Appearing Thyroid Glands on Tc-99m Sestamibi Breast Scintimammography
Authors: CRAIG D. KORBIN, IRAJ KHALKHALI, JOHN A. CUTRONE, LINDA DIGGLES, ISMAEL MENA
Journal: Clinical Nuclear Medicine (1995)

Of 507 breast scintimammograms performed using Tc-99m sestamibi, 34 patients were incidentally found to have abnormal appearing thyroid glands. The authors sought to investigate the clinical significance and/or ascertain an extraneous causative factor for these findings. One cold thyroid nodule was detected and was proven benign through biopsy. Two cases of subacute and chronic thyroiditis were proven, and it is possible that additional patients had this disease process. Focal areas of increased thyroid Tc-99m sestamibi uptake were observed in eight patients and probably represent parathyroid adenomas, nonautonomous hyperfunctioning thyroid nodules, or nontoxic multinodular goiter. The results did not yield an extraneous causative factor, underlying pathology, or clinically significant disease in all of the patients investigated, but the findings suggest a need for careful evaluation of any unusual uptake in the thyroid gland and the rest of the image. The authors do not recommend investigation of all abnormal appearing thyroid glands on Tc-99m sestamibi scintimammography. However, clinical correlation should be recommended.
Crossing Species Boundaries and Making Human-Nonhuman Hybrids: Moral and Legal Ramifications
Authors: A. M. Chakrabarty
Journal: The American Journal of Bioethics (2003)

(2003). Crossing Species Boundaries and Making Human-Nonhuman Hybrids: Moral and Legal Ramifications. The American Journal of Bioethics: Vol. 3, No. 3, pp. 20-21.
Theoretical Basis of Indicator-Dilution Methods For Measuring Flow and Volume
Authors: Kenneth L. Zierler
Journal: Circulation Research (1962)

The purpose here is to inquire into the justification of the use of the indicator-dilution principle for measurement of fluid flow and volume.What is the validity of the formal expressions?Upon what assumptions are they based?What are the effects of specified violations of these assumptions?An indicator, in the sense used here, is a substance that permits observations of some element of volume of the fluid under study.The indicator shows the position of the element of volume in space and with respect to time, and distinguishes the indicated element from all other elements of volume.In practice, a known quantity of indicator is introduced into a fluid flowing at unknown rate through a system of unknown volume.Fluid is sampled or monitored at one or more points downstream from the plane of introduction and the concentration of indicator, diluted by the parent fluid, is measured as a function of time.Indicator may be introduced into the system in any of a number of ways, usually either only once as rapidly as possible (sudden injection) or continuously at constant rate (constant injection).It is claimed that from a knowledge only of the quantity of indicator injected (or of the rate of its injection for the case of constant injection) and of the observed concentration of diluted indicator at the sampling site, over appropriate time intervals, both flow and volume can be calculated.The validity of this statement has been argued effectively by Stewart, 1 -4 Hamilton and his colleagues, 5
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
Authors: Chi-Jen Lee, René Dubos
Journal: The Journal of Experimental Medicine (1972)

The metabolism of adenosine 3',5'-monophosphate (cyclic AMP) was studied in specific pathogen-free mice exposed to neonatal infection with mouse enterovirus or to malnutrition during early life. Metabolic activity was determined by measuring the turnover of cyclic AMP-8-(14)C to respiratory (14)CO(2), its incorporation into various organs and plasma, and the binding activity of synaptosome for cyclic AMP. Early malnutrition increased the catabolism of cyclic AMP as measured by expiration in respiratory CO(2). The level of cyclic AMP was lower in plasma and its incorporation into various tissues was decreased in infected and malnourished animals. Metabolic products of cyclic AMP were isolated from plasma by ion exchange chromatography. Cyclic AMP-8-(14)C had completely disappeared 9 hr after injection. Fewer metabolites of cyclic AMP were detected in infected or malnourished groups than in controls and the metabolic reaction from 5'-AMP to adenosine seemed to be slow in these animals. The ability to incorporate cyclic AMP to synaptosome was also impaired in the experimental groups. The concentrations of brain cyclic AMP were lower in infected or malnourished animals than in controls. Depression of accumulation of cyclic AMP probably resulted from excessive activity of phosphodiesterase, rather than from impairment of adenyl cyclase. Intraperitoneal administration of theophylline brought the activity level of phosphodiesterase to normal in infected or malnourished mice; this fact probably accounted for enhanced accumulation of brain cyclic AMP.
Cytoplasmic Tyrosine Phosphatase Shp2 Coordinates Hepatic Regulation of Bile Acid and FGF15/19 Signaling to Repress Bile Acid Synthesis
Authors: Shuangwei Li, Diane D.F. Hsu, Bing Li, Xiaolin Luo, Nazilla Alderson, Liping Qiao, Lina Ma, Helen H. Zhu, Zhao He, Kelly Suino-Powell, Kaihong Ji, Jiefu Li, Jianhua Shao, H. Eric Xu, Tiangang Li, Gen-Sheng Feng
Journal: Cell Metabolism (2014)
Supine Cross-Table Lateral Chest Roentgenogram for the Detection of Pericardial Effusion
Authors: James A. Heinsimer
Journal: JAMA (1987)

We performed a prospective, blinded, controlled study to test the hypothesis that supine cross-table lateral chest roentgenograms might have an advantage over conventional lateral chest roentgenograms for the detection of pericardial effusion using the epicardial fat stripe sign. In comparison with echocardiography as the gold standard, we found that supine cross-table lateral chest roentgenograms had greater sensitivity (51%) for pericardial effusions than conventional lateral chest roentgenograms (sensitivity, 31%). Specificity was essentially the same for both techniques. A large pericardial effusion was more readily detected by supine cross-table lateral chest roentgenograms (86%) than by the conventional lateral chest roentgenograms (36%). We conclude that a supine cross-table lateral chest roentgenogram should be included in the evaluation of patients with suspected pericardial effusion or in patients in whom a large cardiac silhouette is detected on a standard chest roentgenogram.
Second‐line mitoxantrone, etoposide, and cytarabine for acute myeloid leukemia: A single‐center experience
Authors: Holbrook E. Kohrt, Samit Patel, Michelle Ho, Terri Owen, Daniel A. Pollyea, Ravindra Majeti, Jason Gotlib, Steve Coutre, Michaela Liedtke, Caroline Berube, Ash A. Alizadeh, Bruno C. Medeiros
Journal: American Journal of Hematology (2010)

Abstract The majority of patients with acute myeloid leukemia (AML) will require second‐line chemotherapy for either relapsed or refractory disease. Currently, only allogeneic hematopoietic cell transplantation (HCT) offers a curative option in this setting and no preferred regimen has been established. The reported efficacy of second‐line regimens is widely disparate, thus limiting informed clinical decision making. A retrospective review of 77 patients receiving therapy between 2001 and 2008 with relapsed, 42, and refractory, 35, AML was performed to determine overall response rate and survival following mitoxantrone (8 mg/m 2 /day), etoposide (100 mg/m 2 /day), and cytarabine (1,000 mg/m 2 /day) chemotherapy administered over 5 days. Among 77 patients (median age of 54 years and 64% intermediate risk karyotype) with median follow‐up of 153 days, 18% achieved a complete response and 8% a morphologic leukemia‐free state. Fifty‐seven (74%) experienced treatment failure, 10 of whom achieved a remission after additional therapy. Median overall survival (OS) was 6.8 months. Among patients achieving a response, 50% received consolidation with allogeneic HCT, autologous HCT (5%), or consolidation chemotherapy alone (45%). A nonsignificant trend in overall response (50%, 27%, and 23.8%) and median OS (8.3, 6.8, and 4.7 months) was observed by cytogenetic stratification into favorable, intermediate, and unfavorable risk. Patients with refractory versus relapsed disease had similar overall responses (20% and 31%, P = 0.41) and median OS (5.3 and 7.6 months, P = 0.36). Despite risk stratification by the European Prognostic Index, our series demonstrates inferior rates of response and survival, illustrating the limited activity of this regimen in our cohort. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.
Burns in the developing world and burn disasters
Authors: Rajeev B Ahuja, Sameek Bhattacharya
Journal: BMJ (2004)

Developing countries have a high incidence of burn injuries, creating a formidable public health problem. High population density, illiteracy, and poverty are the main demographic factors associated with a high risk of burn injury. The exact number of burns is difficult to determine: judicious extrapolation suggests that India, with a population of over 1 billion, has 700 000 to 800 000 burn admissions annually. The high incidence makes burns an endemic health hazard. Social, economic, and cultural factors interact to complicate the management, reporting, and prevention of burns.

### Epidemiology

The epidemiology of burn injuries is different from that in the developed world. Most burn injuries are sustained by women aged 16-35 years. Women of this age group tend to be engaged in cooking, and most work at floor level in relatively unsafe kitchens and wear loose fitting clothes such as saris, dupatta, etc. Children and elderly people are at relatively less risk because many households still exist as joint families, and the system safeguards these age groups to some extent.

The commonest mode of burn injury is a flame burn. Most such incidents are related to malfunctioning kerosene pressure stoves. These are cheap contraptions without safety features, and burns occur when carbon deposits block the kerosene vapour outlets. Unsupervised and careless handling of firecrackers during the festival of Diwali lead to an increased incidence of injuries during the festival period. Fire is also used in homicide and suicide.

### Problems in management

Burn management in developing countries is riddled with difficulties. Lack of government initiative and low literacy rates preclude effective prevention programmes. Many uneducated households are fraught with superstition, taboos, …
Points: Allergy to purified bovine, porcine, and human insulins
Authors: R L Blandford, H Sewell, A L Edwards, J R Hearnshaw
Journal: BMJ (1983)

time general practice.We would find it helpful to hear from other junior doctors who have tried or managed to arrange job sharing.We feel that an increasing number of doctors will wish to train part time, and we would welcome further discussion on this topic from both senior and junior hospital doctors.
Pro-Oncogenic Role of Alternative p38 Mitogen-Activated Protein Kinases p38γ and p38δ, Linking Inflammation and Cancer in Colitis-Associated Colon Cancer
Authors: Paloma del Reino, Dayanira Alsina-Beauchamp, Alejandra Escós, Ma Isabel Cerezo-Guisado, Ana Risco, Noelia Aparicio, Rafal Zur, Marian Fernandez-Estévez, Elena Collantes, Jose Montans, Ana Cuenda
Journal: Cancer Research (2014)

p38 MAPK signaling has been implicated in the regulation of processes leading to cancer development and progression. Chronic inflammation is a known risk factor for tumorigenesis, yet the precise mechanism of this association remains largely unknown. The related p38αMAPK (MAPK14) proteins p38γ (MAPK12) and p38δ (MAPK13) were recently shown to modulate the immune response, although their role in tumorigenesis remains controversial and their function in inflammation-associated cancer has not been studied. We analyzed the role of p38γ and p38δ in colon cancer associated to colitis using the azoxymethane/dextran sodium sulphate (AOM/DSS) colitis-associated colon cancer model in wild-type (WT), p38γ-, p38δ-, and p38γ/δ-deficient (p38γ/δ(-/-)) mice. We found that p38γ/δ deficiency significantly decreased tumor formation, in parallel with a decrease in proinflammatory cytokine and chemokine production. Analysis of leukocyte populations in p38γ/δ(-/-) mouse colon showed less macrophage and neutrophil recruitment than in WT mice. Furthermore, WT chimeric mice with transplanted p38γ/δ(-/-) bone marrow had less tumors than WT mice transplanted with WT bone marrow, whereas tumor number was significantly increased in p38γ/δ(-/-) chimeric mice with WT bone marrow compared with p38γ/δ(-/-) mice transplanted with p38γ/δ(-/-) bone marrow. Together, our results establish that p38γ and p38δ are central to colitis-associated colon cancer formation through regulation of hematopoietic cell response to injury, and validate p38γ and p38δ as potential targets for cancer therapy.
The Avoidance of Cervical Intraepithelial Neoplasia
Authors: John R. Crouch
Journal: JAMA (1985)

<h3>To the Editor.—</h3> I certainly enjoyed the stimulating editorial in the Dec 7 issue on the pathogenesis of cervical cancer, "CIN or Not to Sin."<sup>1</sup>The logic seemed to march impeccably on until the last sentence, when it appears that we dropped a beat. "Invasive cervical cancer in the diethylstilbestrol and nondiethylstilbestrol patient may be a preventable disease by (1) continuous cytological and colposcopic screening... and (2) the use of condoms...." The data itself suggests another means: (3) strongly recommend that the healthy thing to do would be for an adult virginal woman to marry an adult virginal man in a monogamous, faithful relationship lasting a (long and healthy) lifetime. But, silly me, that would imply a moral tone to the suggestion and besides, in our present-day liberated and post-sexual-revolution society, that is certainly too radical an idea to offer in health education to our young people. So, pass