tbuckley/cabot-search huggingface dataset:
Lentivirus Mediated Delivery of Neurosin Promotes Clearance of Wild-type α-Synuclein and Reduces the Pathology in an α-Synuclein Model of LBD
Authors: Brian Spencer, Sarah Michael, Jay Shen, Kori Kosberg, Edward Rockenstein, Christina Patrick, Anthony Adame, Eliezer Masliah
Journal: Molecular Therapy (2012)

Neurosin is a predominant serine protease in the central nervous system (CNS) and has been shown to play a role in the clearance of α-synuclein (α-syn) which is centrally involved in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Although it has been previously shown that neurosin and α-syn colocalize and that neurosin degrades α-syn aggregates in vitro, it is not clear if neurosin is dysregulated in the brains of patients with PD/DLB and to what extent delivery of neurosin into the CNS might ameliorate the deficits associated with α-syn accumulation in vivo. We analyzed the levels of neurosin in the brains of patients with PD/DLB and in α-syn transgenic (tg) models. With increased accumulation of α-syn, we observed decreased neurosin expression. Lentiviral vector (LV) driven expression of neurosin in neuronal cell cultures reduced the accumulation of wild type but not A53T α-syn and prevented α-syn associated toxicity. Neuropathological analysis following delivery of LV-Neurosin to α-syn tg mice resulted in reduced accumulation of α-syn and reversal of neurodegenerative alterations in wild type but not A53T α-syn tg mice. Therefore, viral vector driven expression of neurosin may warrant further investigation as a potential therapeutic tool for DLB. Neurosin is a predominant serine protease in the central nervous system (CNS) and has been shown to play a role in the clearance of α-synuclein (α-syn) which is centrally involved in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Although it has been previously shown that neurosin and α-syn colocalize and that neurosin degrades α-syn aggregates in vitro, it is not clear if neurosin is dysregulated in the brains of patients with PD/DLB and to what extent delivery of neurosin into the CNS might ameliorate the deficits associated with α-syn accumulation in vivo. We analyzed the levels of neurosin in the brains of patients with PD/DLB and in α-syn transgenic (tg) models. With increased accumulation of α-syn, we observed decreased neurosin expression. Lentiviral vector (LV) driven expression of neurosin in neuronal cell cultures reduced the accumulation of wild type but not A53T α-syn and prevented α-syn associated toxicity. Neuropathological analysis following delivery of LV-Neurosin to α-syn tg mice resulted in reduced accumulation of α-syn and reversal of neurodegenerative alterations in wild type but not A53T α-syn tg mice. Therefore, viral vector driven expression of neurosin may warrant further investigation as a potential therapeutic tool for DLB.
Scintigraphic Evaluation of a Patient with Enterocutaneous Fistulas Using Tc-99m Latex Particles
Authors: B E CANER, M T ERCAN, G ERBENGI, L O KAPUCU, O ARAN, Y SANAC, C F BEKDIK
Journal: Clinical Nuclear Medicine (1991)

A patient with longstanding enterocutaneous fistulas was studied. Gastrointestinal scintigraphy following the oral administration of Tc-99m latex particles was useful in understanding the pathophysiologic status of the patient, and it provided not only excellent morphologic detail, but quantitative functional information as well.
Inherited combined deficiency of factor V and factor VIII: Report of a case with normal factor VIII antigen and ristocetin‐induced platelet aggregation
Authors: P. L. Cimo, J. L. Moake, M. F. Gonzalez, E. A. Natelson, K. R. Fox
Journal: American Journal of Hematology (1977)

Abstract A patient with inherited combined deficiency of factor V and factor VIII is reported, who demonstrated normal levels of factor VIII antigen and plasma co‐factor for ristocetin‐induced platelet aggregation. The relationship of this condition to classical hemophilia and von Willebrand's disease is discussed. The data presented suggest that multiple loci on at least 2 chromosomes are necessary for the normal expression of factor VIII activity.
Preoperative secundum atrial septal defect with coexisting sinus node and atrioventricular node dysfunction.
Authors: E B Clark, J D Kugler
Journal: Circulation (1982)

Sinus node dysfunction in patients after repair of the secundum atrial septal defect has been ascribed to surgical damage. We studied 15 consecutive patients with secundum atrial septal defect before operative intervention. Noninvasive testing included 34-hour electrocardiographic monitoring and a standard 13-lead ECG. Intracardiac electrophysiologic techniques included corrected sinus node recovery time, sinoatrial conduction time, His bundle recording to measure AH and HV intervals, the atrial pacing rate at which atrioventricular node Wenckebach occurred, and atrioventricular nodal refractory period. The ECG revealed an ectopic atrial rhythm in two patients. Intracardiac electrophysiology showed an abnormal corrected sinus node recovery time (range -40 to 800 msec) in 10 patients. Five patients had evidence of atrioventricular nodal dysfunction with prolonged AH interval or abnormal atrial pacing rate at which atrioventricular Wenckebach occurred. These data indicate that sinus node dysfunction or atrioventricular node dysfunction were present before surgical intervention.
Points from Letters: Dental Anaesthesia
Authors: A. M. Danziger
Journal: BMJ (1967)

example-English doctors.Surely the sen- sible thing for the Government of Pakistan would be to encourage these doctors to return to Pakistan, and if necessary " exploit" the services of their wives.England may suffer by losing these qualified people, but surely Pakistan's need of their services is even greater.The B.M.A. has played a great part in medical history, and surely its sister associa- tion, with Professor Hamid Ali Khan in the chair, could follow its example in this way and attempt the abolition of the reverse "'colour bar."I hope many of my fellow- countrymen will pluck up courage to fight this absurd undemocratic law and injustice.I also must remain anonymous.-Iam, etc., ANON.
P106 Reduction of inappropriate oxygen prescriptions by a home oxygen service
Authors: A. Y. Yates, C. C. Chamberlain, H. G. B. Bakere
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Home Oxygen in England costs around £110 million yet it is estimated that 30% of patients derive no clinical benefit (DH, 2010).1 In addition oxygen can be harmful if used inappropriately. The RD&amp;E Home Oxygen Service was set up in 2008 to provide a comprehensive oxygen assessment service for all adult patients requiring Long Term Oxygen Therapy (LTOT) including the provision of follow-up in the patient9s home. 1044 patients have been seen by this service so far, and 63 concentrators removed following assessment by the home oxygen team. <h3>Methods</h3> We evaluated retrospectively the patients who had oxygen removed. The characteristics of this population were investigated including reason for removal, whether an oxygen assessment had been undertaken and the appropriateness of oxygen prescription. <h3>Results</h3> On assessment 85% (54/63) had saturations &gt;92% and 49% (31/63) were not using their oxygen. Of the 63 patients who had their oxygen removed more patients (53%) had their LTOT initiated in Primary Care. These patients therefore received no formal assessment prior to initiation. When assessed 67% did not meet the criteria for LTOT. Of the 63 those established on LTOT by the Home Oxygen Service, it was primarily in the context of an inpatient stay. In these cases adequate follow-up and review allowed oxygen to be removed once stable. The economic saving from the removal of inappropriate oxygen is considerable. 60% (38/60) no longer required oxygen therapy amounting to a cost saving of £20 330. 39% were re-categorised to a lower tariff but 17% proved difficult to wean and continued on Short Burst Oxygen (SBOT) despite inadequate evidence for this therapy. <h3>Conclusion</h3> Our experience suggests as integrated oxygen service allows a more robust approach to oxygen prescription and monitoring. It reduces the risk of harm from oxygen prescription, and unnecessary prescriptions. This has both financial and medical benefits. Direct prescription of LTOT from primary care by comparison carries a risk of inadequate initial assessment and follow-up.
Four and a half year follow up of women with dyskaryotic cervical smears.
Authors: A Fletcher, N Metaxas, C Grubb, J Chamberlain
Journal: BMJ (1990)

OBJECTIVE--To determine the proportion of women with mild or moderate dyskaryosis in cervical smears who (a) progress to cervical intraepithelial neoplasia grade III or worse or (b) regress. DESIGN--Four and a half year cytological follow up study of women with mild or moderate dyskaryosis in cervical smears. SETTING--666 Women (mean age 28 (SD 8) years; range 14-74) found to have borderline, mild, or moderate dyskaryosis on routine screening. RESULTS--45 Women (6.8%) had a cone biopsy recommended on the basis of an abnormal follow up smear (severe dyskaryosis suggestive of cervical intraepithelial neoplasia grade III or invasive cancer), and in one patient cervical intraepithelial neoplasia grade III was reported in a biopsy specimen after dilatation and curettage. Life table analysis gave a 14% probability of a patient being recommended for a biopsy after four and a half years of follow up (95% confidence interval 12% to 15%). There was a significant excess incidence of invasive cancer of the cervix in the series compared with the general population (five cases observed compared with less than 0.1 expected). 157 Patients (24%) showed reversion to a normal cell pattern sustained in several smears over more than 18 months but a single negative smear was an unreliable indicator of apparent regression. Having two successive smears showing mild dyskaryosis or a smear at any time showing moderate dyskaryosis was a significant predictor of a subsequent severely dyskaryotic smear. CONCLUSIONS--Women found to have mild or moderate dyskaryosis in cervical smears should be kept under regular surveillance. The optimum management of these patients--by cytology or colposcopy--needs to be determined by randomised controlled trials.
A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure.
Authors: U Elkayam, J Amin, A Mehra, J Vasquez, L Weber, S H Rahimtoola
Journal: Circulation (1990)

We performed a prospective, randomized, double-blind, crossover study to compare the efficacy and safety of vasodilation with the calcium entry blocker nifedipine with that of isosorbide dinitrate (ISDN) and their combination as treatment for heart failure. Twenty-eight patients with New York Heart Association Functional class II or III chronic heart failure due to left ventricular systolic dysfunction were studied. All patients were maintained on a constant dose of digitalis and diuretics throughout the study. Eight weeks of therapy with nifedipine alone or in combination with ISDN resulted in a significantly higher incidence of heart failure deterioration necessitating hospitalizations and/or additional diuretics. Twenty-four percent of patients required hospitalization during nifedipine therapy and 26% required hospitalization during nifedipine-ISDN combination therapy in comparison to 0% requiring hospitalization during ISDN therapy alone. The total number of heart failure-worsening episodes was nine among patients on nifedipine, three among patients on ISDN (p less than 0.09 versus nifedipine), and 21 among patients on nifedipine-ISDN combination (p less than 0.001 versus nifedipine, p less than 0.0001 versus ISDN). Premature discontinuation of drug administration due to clinical deterioration or other side effects occurred in 29% of patients during nifedipine therapy, 5% of patients during ISDN therapy (p = 0.05 versus nifedipine), and 19% of patients during the combination therapy. A comparison of eight patients who demonstrated clinical deterioration on nifedipine with the remainder of the patients demonstrated no significant difference in left ventricular ejection fraction (0.24 +/- 0.06 versus 0.23 +/- 0.07) or maximal oxygen uptake during exercise (13 +/- 3 versus 14 +/- 2 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)
Targeting Inflammatory Pathways for Prevention and Therapy of Cancer: Short-Term Friend, Long-Term Foe
Authors: Bharat B. Aggarwal, R.V. Vijayalekshmi, Bokyung Sung
Journal: Clinical Cancer Research (2009)

Abstract Chronic infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and high-calorie diet have been recognized as major risk factors for the most common types of cancer. All these risk factors are linked to cancer through inflammation. Although acute inflammation that persists for short-term mediates host defense against infections, chronic inflammation that lasts for long term can predispose the host to various chronic illnesses, including cancer. Linkage between cancer and inflammation is indicated by numerous lines of evidence; first, transcription factors nuclear factor-κB (NF-κB) and signal transducers and activators of transcription 3 (STAT3), two major pathways for inflammation, are activated by most cancer risk factors; second, an inflammatory condition precedes most cancers; third, NF-κB and STAT3 are constitutively active in most cancers; fourth, hypoxia and acidic conditions found in solid tumors activate NF-κB; fifth, chemotherapeutic agents and γ-irradiation activate NF-κB and lead to chemoresistance and radioresistance; sixth, most gene products linked to inflammation, survival, proliferation, invasion, angiogenesis, and metastasis are regulated by NF-κB and STAT3; seventh, suppression of NF-κB and STAT3 inhibits the proliferation and invasion of tumors; and eighth, most chemopreventive agents mediate their effects through inhibition of NF-κB and STAT3 activation pathways. Thus, suppression of these proinflammatory pathways may provide opportunities for both prevention and treatment of cancer.
Objective assessment of technical skills in surgery
Authors: Sanjeev Sharma
Journal: BMJ (2004)

Editor—Moorthy et al describe a remarkable new tool to help in the acquisition and assessment of surgical skills.1 Assessment is reliable, valid, objective, and reproducible. However, the article concentrates largely on technical skills.

The requirements of a surgeon—which have remained the same over the past 250 years—are sound decision making and surgical prowess. Operations need to be performed well; equally, they need to be done for the right reasons.

The whole process of adult learning is a combination of theoretical knowledge, acquisition of skills, and application of these professionally.2 Implicit in this process is a concept of reflective thinking. Reflection integrates new skills and facts with previous knowledge and experience. Without reflection, the learning of new skills happens without being related to a meaningful framework. The last step in this is the critical evaluation of the whole process through internal questioning or self assessment.

The assessment needs to be of both the skills and the decision making process, otherwise the whole exercise becomes simply a way to tick boxes.
Platelet microbicidal proteins and neutrophil defensin disrupt the Staphylococcus aureus cytoplasmic membrane by distinct mechanisms of action.
Authors: M R Yeaman, A S Bayer, S P Koo, W Foss, P M Sullam
Journal: Journal of Clinical Investigation (1998)

Platelet microbicidal proteins (PMPs) are hypothesized to exert microbicidal effects via cytoplasmic membrane disruption. Transmission electron microscopy demonstrated a temporal association between PMP exposure, damage of the Staphylococcus aureus cytoplasmic membrane ultrastructure, and subsequent cell death. To investigate the mechanisms of action of PMPs leading to membrane damage, we used flow cytometry to compare the effects of two distinct PMPs (thrombin-induced PMP-1 [tPMP-1] or PMP-2) with human neutrophil defensin-1 (hNP-1) on transmembrane potential (Deltapsi), membrane permeabilization, and killing of S. aureus. Related strains 6850 (Deltapsi -150 mV) and JB-1 (Deltapsi -100 mV; a respiration-deficient menadione auxotroph of 6850) were used to assess the influence of Deltapsi on peptide microbicidal effects. Propidium iodide (PI) uptake was used to detect membrane permeabilization, retention of 3,3'-dipentyloxacarbocyanine (DiOC5) was used to monitor membrane depolarization (Deltapsi), and quantitative culture or acridine orange accumulation was used to measure viability. PMP-2 rapidly depolarized and permeabilized strain 6850, with the extent of permeabilization inversely related to pH. tPMP-1 failed to depolarize strain 6850, but did permeabilize this strain in a manner directly related to pH. Depolarization, permeabilization, and killing of strain JB-1 due to PMPs were significantly less than in strain 6850. Growth in menadione reconstituted Deltapsi of JB-1 to a level equivalent to 6850, and was associated with greater depolarization due to PMP-2, but not tPMP-1. Reconstitution of Deltapsi also enhanced permeabilization and killing of JB-1 due to tPMP-1 or PMP-2. Both PMP-2 and tPMP-1 caused significant reductions in viability of strain 6850. In contrast to tPMP-1 or PMP-2, defensin hNP-1 depolarized, permeabilized, and killed both strains 6850 and JB-1 equally, and in a manner directly related to pH. Collectively, these data indicate that membrane dysfunction and cell death due to tPMP-1, PMP-2, or hNP-1 likely involve different mechanisms. These findings may also reveal new insights into the microbicidal activities versus mammalian cell toxicities of antimicrobial peptides.
Acupuncture Without the Puncture
Authors: Jerome J. Cunningham
Journal: JAMA (1976)

<h3>To the Editor.—</h3> Even though acupuncture is of Chinese invention, the Japanese have widely practiced this form of folk medicine for many centuries. Occasionally, an acupuncture needle may accidentally break off during therapy and if a roentgenogram is taken, the needle becomes recognizable as a slender metal wire imbedded in an organ or in soft tissues. A more dramatic roentgenographic pattern may be observed in<i>hari</i>, a form of acupuncture peculiar to Japan. To perform<i>hari</i>, the practitioner inserts thin gold needles into the subcutaneous tissues and cuts off the needle at the skin surface. When roentgenograms of these patients are seen, slender metal wires are visible that may number in the hundreds.<sup>1</sup> We have recently taken roentgenograms of a patient who practices Japanese folk medicine with metal foreign bodies quite different from those employed in either acupuncture or<i>hari</i>. <h3>Report of a Case.—</h3> An elderly Japanese woman was
Regulation of Animal Experimentation: An Apology
Authors: Thomas D. Overcast
Journal: JAMA (1986)

<h3>To the Editor.—</h3> I want to point out to you and your readers that substantial portions of an article that I recently published inThe Journal<sup>1</sup>were taken word-for-word and sentence-for-sentence from an earlier article by Chambers and Hines (reference 32 in my article).<sup>2</sup>The responsibility for this is mine and mine alone. My coauthor had no hand in the preparation of the first draft of the manuscript from which we then jointly worked. Plagiarism is a cardinal sin of the highest magnitude for which there is no excuse, and I have none to offer. I can only conclude that it was a horrendous but unintentional mistake. After carefully examining all of the circumstances surrounding my preparation of the animal regulation manuscript, I would like to share some important lessons that I have learned. From these lessons I have derived four principles that will help ensure the integrity
IBS-associated phylogenetic unbalances of the intestinal microbiota are not reverted by probiotic supplementation
Authors: Simone Maccaferri, Marco Candela, Silvia Turroni, Manuela Centanni, Marco Severgnini, Clarissa Consolandi, Piero Cavina, Patrizia Brigidi
Journal: Gut Microbes (2012)

IBS is a prevalent functional gastrointestinal disorder, in which the microbiota has been demonstrated to play a role. An increasing number of studies have suggested how probiotics may alleviate IBS symptoms and several mechanisms of action have been proposed. In the present study we characterized the intestinal microbiota of 19 subjects suffering from diagnosed IBS using a fully validated High Taxonomic Fingerprint Microbiota Array (HTF-Microbi.Array). We demonstrated that the IBS microbiota is different from that of healthy individuals due to an unbalance in a number of commensal species, with an increase in relative abundance of lactobacilli, B. cereus and B. clausii, bifidobacteria, Clostridium cluster IX and E. rectale, and a decrease in abundance of Bacteroides/Prevotella group and Veillonella genus. Additionally, we demonstrated that some bacterial groups of the human intestinal microbiota, recently defined as pathobionts, are increased in concentration in the IBS microbiota. Furthermore, we aimed at investigating if the daily administration of a novel probiotic yogurt containing B. animalis subsp lactis Bb12 and K. marxianus B0399, recently demonstrated to have beneficial effects in the management of IBS symptoms, could impact on the biostructure of IBS microbiota, modulating its composition to counteract putative dysbiosis found in IBS subjects. Notably, we demonstrated that the beneficial effects associated to the probiotic preparation are not related to significant modifications in the composition of the human intestinal microbiota.
To Drink (Moderately) or Not to Drink?
Authors: Charles S. Lieber
Journal: New England Journal of Medicine (1984)

Throughout the history of humanity, alcoholic beverages have been widely used for their pleasing taste and their mood-altering effects. However, the use of alcohol has evoked strong opposition, because of the potential for abuse and the associated adverse effects on safety and health. In large urban areas, one of the complications of alcohol abuse — cirrhosis of the liver — is now the second most common cause of all deaths in the age group of 25 to 44 years and the third in the group 45 to 64.1 Arguments for or against control of intake have evoked powerful emotional responses, . . .
State of Virginia launches legal challenge to US health reforms
Authors: J. H. Tanne
Journal: BMJ (2010)

A US federal judge upheld a challenge on 2 August by the state of Virginia to the US health reform law passed in March. The next step is a summary judgment hearing on 18 October to determine whether the reform is unconstitutional, but the case is likely to take years to work its way through the courts and may go as far as the Supreme Court.

Virginia’s attorney general, Ken Cuccinelli II, argued that the health reform law required people to buy health insurance or pay a penalty and thus exceeded the powers granted to the federal government by the commerce clause of the US constitution. The clause gives the federal government the power to regulate interstate commerce such as health insurance and to impose taxes. He said that …