tbuckley/cabot-search huggingface dataset:
Rhinoviruses and Common Colds
Authors: C H Andrewes
Journal: Annual Review of Medicine (1966)

virus, also by some enteroviruses and by Mycoplasma pneumoniae. Other colds can be trans­ mitted to volunteers by means of filtration of nasal washings from which no virus has been cultivable. Of the viruses concerned in colds in adults and which have been cultivated, the rhinoviruses seem to be the most important. They are rather more difficult to isolate and study than are other known respiratory viruses, and it seems possible that, as techniques are improved, more and more colds will turn out to be due to rhinoviruses. This review will deal with recent additions to knowledge about the properties of rhinoviruses, their role in disease, and prospects of immunization against them. The sec­ tion on epidemiology will be concerned also with other respiratory viruses. There have recently been published two review articles (1, 2) on rhinoviruses; also two books on common colds, one directed to medical (3), the other to lay readers (4).
Renal 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase Is an Important Determinant of AKI Severity after Ischemia-Reperfusion
Authors: Edwin K. Jackson, Elizabeth V. Menshikova, Zaichuan Mi, Jonathan D. Verrier, Rashmi Bansal, Keri Janesko-Feldman, Travis C. Jackson, Patrick M. Kochanek
Journal: Journal of the American Society of Nephrology (2015)

A positional isomer of 3′,5′-cAMP, 2′,3′-cAMP, is produced by kidneys in response to energy depletion, and renal 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) metabolizes 2′,3′-cAMP to 2′-AMP; 2′,3′-cAMP is a potent opener of mitochondrial permeability transition pores (mPTPs), which can stimulate autophagy. Because autophagy protects against AKI, it is conceivable that inhibition of CNPase protects against ischemia-reperfusion (IR) –induced AKI. Therefore, we investigated renal outcomes, mitochondrial function, number, area, and autophagy in CNPase-knockout (CNPase −/− ) versus wild-type (WT) mice using a unique two–kidney, hanging–weight model of renal bilateral IR (20 minutes of ischemia followed by 48 hours of reperfusion). Analysis of urinary purines showed attenuated metabolism of 2′,3′-cAMP to 2′-AMP in CNPase −/− mice. Neither genotype nor IR affected BP, heart rate, urine volume, or albumin excretion. In WT mice, renal IR reduced 14 C-inulin clearance (index of GFR) and increased renal vascular resistance (measured by transit time nanoprobes) and urinary excretion of kidney injury molecule-1 and neutrophil gelatinase–associated lipocalin. IR did not affect these parameters in CNPase −/− mice. Histologic analysis revealed that IR induced severe damage in kidneys from WT mice, whereas histologic changes were minimal after IR in CNPase −/− mice. Measurements of renal cardiolipin levels, citrate synthase activity, rotenone–sensitive NADH oxidase activity, and proximal tubular mitochondrial and autophagosome area and number (by transmission electron microscopy) indicted accelerated autophagy/mitophagy in injured CNPase −/− mice. We conclude that CNPase deletion attenuates IR-induced AKI, in part by accelerating autophagy with targeted removal of damaged mitochondria.
Changes in intracellular sodium and pH during ischaemia–reperfusion are attenuated by trimetazidine Comparison between low- and zero-flow ischaemia
Authors: H El Banani
Journal: Cardiovascular Research (2000)

Objective: The aim of this study was to investigate whether trimetazidine (TMZ; 10−6M), which has been shown to inhibit fatty acid oxidation, reduces the ionic imbalance induced by ischaemia and reperfusion, especially through an attenuation in intracellular changes in H+ and Na+. Methods: Isovolumic rat hearts receiving 5.5 mM glucose and 1.2 mM palmitate as metabolic substrates were exposed to zero-flow ischaemia (TI) or low-flow ischaemia (LFI — coronary flow decreased by an average of 90%) (30 min at 37°C) and then reperfused. 23Na nuclear magnetic resonance (NMR) spectroscopy was used to monitor intracellular Na+ (Na+i) and 31P NMR spectroscopy was used to monitor intracellular pH (pHi). Results: During LFI the major effect of TMZ was a significant reduction in intracellular acidosis, whereas during TI the main effect of TMZ was a significant reduction in Na+i gain. In addition, the further gain in Na+i that occurred during the first minutes of reperfusion following TI, and to a far lesser extent following LFI, was suppressed in TMZ-treated hearts and also suppressed when hearts were perfused without fatty acid. In both LFI and TI, TMZ-induced attenuation of ionic imbalance was associated with a significantly improved recovery of ventricular function on reperfusion, as assessed by a lower increase in diastolic pressure and an increased recovery of developed pressure. Conclusion: Our data provide evidence that specific myocardial metabolic modulation plays a significant role in reducing ionic imbalance during ischaemia and reperfusion.
A new biomarker in monitoring breast cancer: CA 549.
Authors: R A Beveridge, D W Chan, D Bruzek, D Damron, K R Bray, P K Gaur, D S Ettinger, R C Rock, M S Shurbaji, F P Kuhajda
Journal: Journal of Clinical Oncology (1988)

Serum biomarkers are not very reliable in assessing outcome or predicting recurrence of breast cancer. Clinically, carcinoembryonic antigen (CEA) is widely used and is elevated in a majority of patients with metastatic breast cancer. However, it is falsely elevated in a wide range of nonmalignant conditions and correlates poorly with disease progression. We evaluated a newly described monoclonal antibody, CA 549, in an immunoradiometric assay which uses two monoclonal antibodies directed against tumor and milk fat globule membranes. CA 549 and CEA were studied in 682 patients, 331 of whom had breast diseases and 99 of whom were followed with multiple serum samples. Of 69 patients with benign breast diseases, 1.5% had elevated CA 549, 0% of 30 pregnant women had elevated CA 549, and 26% of patients with nonmalignant liver disease had CA 549 elevation. In metastatic cancer of prostate, ovary, endometrium, colon, and lung CA 549 was elevated in 12% to 50% of cases with levels less than 120 U/mL. In breast cancer, CA 549 was elevated in 11% of 88 patients who received adjuvant chemotherapy and had no evidence of metastasis; in 23% of 16 patients in complete remission after chemotherapy; in 63% of 52 patients in partial remission after therapy; and in 83% of 106 patients with progression of breast cancer compared with 63% with elevated CEA (P = .001). In diseases of the breast, CA 549 has a sensitivity In diseases of the breast, CA 549 has a sensitivity and specificity of 77% and 92% v 61% and 92% for CEA. Of 99 patients serially monitored with clinically documented breast cancer progression, regression, or stability of disease, CA 549 was statistically significantly superior to CEA in monitoring a greater than 25% change in those patients with metastatic progression (P = .03). CA 549 is a new serum marker that should be control tested in prospective clinical trials alone or in conjunction with other markers.
Neuropeptides and Inflammation: The Role of Substance P
Authors: D G Payan
Journal: Annual Review of Medicine (1989)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
ISAAC Malta: Changes in geographical distribution of wheezing children in Malta between 1994 and 2002
Authors: Peter Fsadni, Claudia Fsadni, Maxine Montefort, Stephen Montefort
Journal: European Respiratory Journal (2011)

Introduction:  Malta is one of the centres which participated in the Phase 1 and 3 of The International Study of Asthma and Allergies in Childhood (ISAAC).   Aim:  To investigate changes in the geographical distribution of wheezing in the Maltese Islands.   Methods:  ISAAC Malta Phase 1 was carried out in 1994 with 3506 participants from 24 schools for the 5 to 8 year old age group and 4184 participants from 25 schools for the 13 to 15 year old age group.  ISAAC Malta Phase 3 in 2001 studied 3800 from 44 schools and 4139 children from 18 schools in the 5 to 8 and 13 to 15 year old age groups respectively.   Results:  In the younger age group there was an increase from 8.8% to 14.8% (p  The prevalence of current wheezing in the older age group remained stable (16% to 14.6% p=0.08). A decline in current wheezing (p=0.5) was observed in Central West (16.31% vs 11.2), West (17.5% vs 12.6%) and South (14.8% vs 11.2%) while three regions reported an increase in wheezing.   Conclusions:  A strong genetic component together with environmental factors must influence the geographical distribution of wheezing in the Maltese Islands.
Organizational characteristics, outcomes, and resource use in 78 Brazilian intensive care units: the ORCHESTRA study
Authors: Marcio Soares, Fernando A. Bozza, Derek C. Angus, André M. Japiassú, William N. Viana, Roberto Costa, Leonardo Brauer, Bruno F. Mazza, Thiago D. Corrêa, André L. B. Nunes, Thiago Lisboa, Fernando Colombari, Alexandre T. Maciel, Luciano C. P. Azevedo, Moyzés Damasceno, Haggeas S. Fernandes, Alexandre B. Cavalcanti, Pedro E. A. A. do Brasil, Jeremy M. Kahn, Jorge I. F. Salluh
Journal: Intensive Care Medicine (2015)
Effect of schedule and maintenance on the antiemetic efficacy of ondansetron combined with dexamethasone in acute and delayed nausea and emesis in patients receiving moderately emetogenic chemotherapy: a phase III trial by the National Cancer Institute of Canada Clinical Trials Group.
Authors: L Kaizer, D Warr, P Hoskins, J Latreille, W Lofters, J Yau, M Palmer, B Zee, M Levy, J Pater
Journal: Journal of Clinical Oncology (1994)

PURPOSE This study examines whether the schedule of ondansetron significantly influences its antiemetic efficacy in the first 24 hours after chemotherapy, whether the administration of oral ondansetron after 24 hours is effective in preventing delayed emesis, and whether the efficacy of ondansetron is preserved over multiple courses of moderately emetogenic chemotherapy. PATIENTS AND METHODS A multicenter double-blind study randomized 302 cancer patients to one of three treatment arms. Arm A received dexamethasone 10 mg intravenously (i.v.) plus ondansetron (Zofran; Glaxo Canada Inc, Toronto, Canada) 8 mg i.v. prechemotherapy plus ondansetron 8 mg orally every 12 hours postchemotherapy for nine doses. Arm B received dexamethasone 10 mg i.v. plus ondansetron 16 mg i.v. prechemotherapy plus placebo orally postchemotherapy in the same schedule as arm A. Arm C received dexamethasone 10 mg i.v. plus ondansetron 8 mg prechemotherapy plus ondansetron 8 mg orally postchemotherapy for one dose followed by placebo orally every 12 hours for eight more doses. Response was assessed by the number of reported episodes of vomiting and by severity of nausea measured on a visual analog scale (VAS). RESULTS The two schedules of ondansetron used in the first 24 hours were no different in their antiemetic efficacy, with similar rates for complete responses (76.7% v 72.0%, P = .472), complete plus major responses (90.2% v 82.0%, P = .135), and severity of nausea (P = .348). Oral ondansetron after 24 hours was more effective than placebo in preventing delayed nausea and emesis, with superior rates of complete responses (59.6% v 42.1%, P = .012 by one-sided test), complete plus major responses (80.9% v 66.3%, P = .018 by one-sided test), and less severe nausea (9.2 mm v 18.6 mm on a 100-mm VAS, P = .002). The efficacy of ondansetron was maintained over subsequent courses of chemotherapy. CONCLUSION The schedule of ondansetron in the first 24 hours does not influence its efficacy. The use of oral maintenance ondansetron is effective in preventing delayed maintenance ondansetron is effective in preventing delayed nausea and emesis after moderately emetogenic chemotherapy.
Population Structure Shapes Copy Number Variation in Malaria Parasites
Authors: Ian H. Cheeseman, Becky Miller, John C. Tan, Asako Tan, Shalini Nair, Standwell C. Nkhoma, Marcos De Donato, Hectorina Rodulfo, Arjen Dondorp, Oralee H. Branch, Lastenia Ruiz Mesia, Paul Newton, Mayfong Mayxay, Alfred Amambua-Ngwa, David J. Conway, François Nosten, Michael T. Ferdig, Tim J. C. Anderson
Journal: Molecular Biology and Evolution (2015)

If copy number variants (CNVs) are predominantly deleterious, we would expect them to be more efficiently purged from populations with a large effective population size (Ne) than from populations with a small Ne. Malaria parasites (Plasmodium falciparum) provide an excellent organism to examine this prediction, because this protozoan shows a broad spectrum of population structures within a single species, with large, stable, outbred populations in Africa, small unstable inbred populations in South America and with intermediate population characteristics in South East Asia. We characterized 122 single-clone parasites, without prior laboratory culture, from malaria-infected patients in seven countries in Africa, South East Asia and South America using a high-density single-nucleotide polymorphism/CNV microarray. We scored 134 high-confidence CNVs across the parasite exome, including 33 deletions and 102 amplifications, which ranged in size from <500 bp to 59 kb, as well as 10,107 flanking, biallelic single-nucleotide polymorphisms. Overall, CNVs were rare, small, and skewed toward low frequency variants, consistent with the deleterious model. Relative to African and South East Asian populations, CNVs were significantly more common in South America, showed significantly less skew in allele frequencies, and were significantly larger. On this background of low frequency CNV, we also identified several high-frequency CNVs under putative positive selection using an FST outlier analysis. These included known adaptive CNVs containing rh2b and pfmdr1, and several other CNVs (e.g., DNA helicase and three conserved proteins) that require further investigation. Our data are consistent with a significant impact of genetic structure on CNV burden in an important human pathogen.
In uncontrolled hypertension, a pharmacist-prescribing intervention reduced blood pressure at 6 months
Authors: David Siegel
Journal: Annals of Internal Medicine (2015)

Source Citation Tsuyuki RT, Houle SK, Charrois TL, et al; RxACTION Investigators. Randomized trial of the effect of pharmacist prescribing on improving blood pressure in the community: the Alberta Clinical Trial in Optimizing Hypertension (RxACTION). Circulation. 2015;132:93-100. 26063762
Cardiac myosin light chain phosphorylation and inotropic effects of a biased ligand, TRV120023, in a dilated cardiomyopathy model
Authors: Madhusudhan Tarigopula, Robert T. Davis, Paul T. Mungai, David M. Ryba, David F. Wieczorek, Conrad L. Cowan, Jonathan D. Violin, Beata M. Wolska, R. John Solaro
Journal: Cardiovascular Research (2015)

Therapeutic approaches to treat familial dilated cardiomyopathy (DCM), which is characterized by depressed sarcomeric tension and susceptibility to Ca2+-related arrhythmias, have been generally unsuccessful. Our objective in the present work was to determine the effect of the angiotensin II type 1 receptor (AT1R) biased ligand, TRV120023, on contractility of hearts of a transgenic mouse model of familial DCM with mutation in tropomyosin at position 54 (TG-E54K). Our rationale is based on previous studies, which have supported the hypothesis that biased G-protein-coupled receptor ligands, signalling via β-arrestin, increase cardiac contractility with no effect on Ca2+ transients. Our previous work demonstrated that the biased ligand TRV120023 is able to block angiotensin-induced hypertrophy, while promoting an increase in sarcomere Ca2+ response. We tested the hypothesis that the depression in cardiac function associated with DCM can be offset by infusion of the AT1R biased ligand, TRV120023. We intravenously infused saline, TRV120023, or the unbiased ligand, losartan, for 15 min in TG-E54K and non-transgenic mice to obtain left ventricular pressure–volume relations. Hearts were analysed for sarcomeric protein phosphorylation. Results showed that the AT1R biased ligand increases cardiac performance in TG-E54K mice in association with increased myosin light chain-2 phosphorylation. Treatment of mice with an AT1R biased ligand, acting via β-arrestin signalling, is able to induce an increase in cardiac contractility associated with an increase in ventricular myosin light chain-2 phosphorylation. AT1R biased ligands may prove to be a novel inotropic approach in familial DCM.
A systematic review of tests predicting ovarian reserve and IVF outcome
Authors: F J Broekmans, J Kwee, D J Hendriks, B W Mol, C B Lambalk
Journal: Human Reproduction Update (2006)

The age-related decline of the success in IVF is largely attributable to a progressive decline of ovarian oocyte quality and quantity. Over the past two decades, a number of so-called ovarian reserve tests (ORTs) have been designed to determine oocyte reserve and quality and have been evaluated for their ability to predict the outcome of IVF in terms of oocyte yield and occurrence of pregnancy. Many of these tests have become part of the routine diagnostic procedure for infertility patients who undergo assisted reproductive techniques. The unifying goals are traditionally to find out how a patient will respond to stimulation and what are their chances of pregnancy. Evidence-based medicine has progressively developed as the standard approach for many diagnostic procedures and treatment options in the field of reproductive medicine. We here provide the first comprehensive systematic literature review, including an a priori protocolized information retrieval on all currently available and applied tests, namely early-follicular-phase blood values of FSH, estradiol, inhibin B and anti-Müllerian hormone (AMH), the antral follicle count (AFC), the ovarian volume (OVVOL) and the ovarian blood flow, and furthermore the Clomiphene Citrate Challenge Test (CCCT), the exogenous FSH ORT (EFORT) and the gonadotrophin agonist stimulation test (GAST), all as measures to predict ovarian response and chance of pregnancy. We provide, where possible, an integrated receiver operating characteristic (ROC) analysis and curve of all individual evaluated published papers of each test, as well as a formal judgement upon the clinical value. Our analysis shows that the ORTs known to date have only modest-to-poor predictive properties and are therefore far from suitable for relevant clinical use. Accuracy of testing for the occurrence of poor ovarian response to hyperstimulation appears to be modest. Whether the a priori identification of actual poor responders in the first IVF cycle has any prognostic value for their chances of conception in the course of a series of IVF cycles remains to be established. The accuracy of predicting the occurrence of pregnancy is very limited. If a high threshold is used, to prevent couples from wrongly being refused IVF, a very small minority of IVF-indicated cases (∼3%) are identified as having unfavourable prospects in an IVF treatment cycle. Although mostly inexpensive and not very demanding, the use of any ORT for outcome prediction cannot be supported. As poor ovarian response will provide some information on OR status, especially if the stimulation is maximal, entering the first cycle of IVF without any prior testing seems to be the preferable strategy.
HbA1c After a Short Period of Monotherapy With Metformin Identifies Durable Glycemic Control Among Adolescents With Type 2 Diabetes
Authors: Phil Zeitler, Kathryn Hirst, Kenneth C. Copeland, Laure El ghormli, Lorraine Levitt Katz, Lynne L. Levitsky, Barbara Linder, Paul McGuigan, Neil H. White, Denise Wilfley
Journal: Diabetes Care (2015)

OBJECTIVE To determine whether clinically accessible parameters early in the course of youth-onset type 2 diabetes predict likelihood of durable control on oral therapy. RESEARCH DESIGN AND METHODS TODAY was a randomized clinical trial of adolescents with type 2 diabetes. Two groups, including participants from all three treatments, were defined for analysis: 1) those who remained in glycemic control for at least 48 months of follow-up and 2) those who lost glycemic control before 48 months. Outcome group was analyzed in univariate and multivariate models as a function of baseline characteristics (age, sex, race/ethnicity, socioeconomic status, BMI, waist circumference, Tanner stage, disease duration, depressive symptoms) and biochemical measures (HbA1c, C-peptide, lean and fat body mass, insulin inverse, insulinogenic index). Receiver operating characteristic curves were used to analyze HbA1c cut points. RESULTS In multivariate models including factors significant in univariate analysis, only HbA1c and insulinogenic index at randomization remained significant (P &amp;lt; 0.0001 and P = 0.0002, respectively). An HbA1c cutoff of 6.3% (45 mmol/mol) (positive likelihood ratio [PLR] 3.7) was identified that optimally distinguished the groups; sex-specific cutoffs were 6.3% (45 mmol/mol) for females (PLR 4.4) and 5.6% (38 mmol/mol) for males (PLR 2.1). CONCLUSIONS Identifying youth with type 2 diabetes at risk for rapid loss of glycemic control would allow more targeted therapy. HbA1c is a clinically accessible measure to identify high risk for loss of glycemic control on oral therapy. Adolescents with type 2 diabetes unable to attain a non–diabetes range HbA1c on metformin are at increased risk for rapid loss of glycemic control.
Years of potential life lost for brain and CNS tumors relative to other cancers in adults in the United States, 2010
Authors: Chaturia Rouse, Haley Gittleman, Quinn T. Ostrom, Carol Kruchko, Jill S. Barnholtz-Sloan
Journal: Neuro-Oncology (2015)

Years of potential life lost (YPLL) complement incidence and survival rates by measuring how much a patient's life is likely to be shortened by his or her cancer. In this study, we examine the impact of death due to brain and other central nervous system (CNS) tumors compared to other common cancers in adults by investigating the YPLL of adults in the United States. Mortality and life table data were obtained from the Centers for Disease Control and Prevention's National Center for Health Statistics Vital Statistics Data for 2010. The study population included individuals aged 20 years or older at death who died from one of the selected cancers. YPLL was calculated by taking an individual's age at death and finding the corresponding expected remaining years of life using life table data. The cancers with the greatest mean YPLL were other malignant CNS tumors (20.65), malignant brain tumors (19.93), and pancreatic cancer (15.13) for males and malignant brain tumors (20.31), breast cancer (18.78), and other malignant CNS tumors (18.36) for females. For both sexes, non-Hispanic whites had the lowest YPLL, followed by non-Hispanic blacks, and Hispanics. Malignant brain and other CNS tumors have the greatest mean YPLL, thereby reflecting their short survival time post diagnosis. These findings will hopefully motivate more research into mitigating the impact of these debilitating tumors.