tbuckley/cabot-search huggingface dataset:
Prodromal Parkinson's disease: hype or hope for disease-modification trials?
Authors: Philipp Mahlknecht, Kathrin Marini, Mario Werkmann, Werner Poewe, Klaus Seppi
Journal: Translational Neurodegeneration (2022)

Abstract The ultimate goal in Parkinson's disease (PD) research remains the identification of treatments that are capable of slowing or even halting the progression of the disease. The failure of numerous past disease-modification trials in PD has been attributed to a variety of factors related not only to choosing wrong interventions, but also to using inadequate trial designs and target populations. In patients with clinically established PD, neuronal pathology may already have advanced too far to be modified by any intervention. Based on such reasoning, individuals in yet prediagnostic or prodromal disease stages, may provide a window of opportunity to test disease-modifying strategies. There is now sufficient evidence from prospective studies to define diagnostic criteria for prodromal PD and several approaches have been studied in observational cohorts. These include the use of PD-risk algorithms derived from multiple established risk factors for disease as well as follow-up of cohorts with single defined prodromal markers like hyposmia, rapid eye movement sleep behavior disorders, or PD gene carriers. In this review, we discuss recruitment strategies for disease-modification trials in various prodromal PD cohorts, as well as potential trial designs, required trial durations, and estimated sample sizes. We offer a concluding outlook on how the goal of implementing disease-modification trials in prodromal cohorts might be achieved in the future.
Middlesex Hospital
Authors: A. Shaw
Journal: BMJ (1859)

into Mliddlesex Hospital, under the care of Mr. Shaw, for fracture of several of the ribs on the right side.For many years he has been subject to chronic bronchitis, and up to the present time has been a patient of a Dispensary for Diseases of the Chest.On this day, while unloading his waggon of beer- barrels at a public house, he fell into the cellar, and struck his side with great force against the edge of a barrel.He was brought to the Hospital within an hour after the accident.Three or four of his ribs, in the central and back part of the right side, were broken, their ends being loose and grating.Over the seat of the injury, for a space of about eight inches square, there was emphysema, marked by the swelling and peculiar crackling feel caused by air contained in the cellular membrane.No blood was perceived in the sputa.The dyspnua was very great.As this was aggravated by the application of the rib-roller, it was removed; and a broad piece of ad- hesive stiapping was drawn firmly over the injured part.The patient being unable to lie down, a bed chair with pillows was provided: he had a purge of calomel and jalap: also a linctus for the cough: and diet of gruel.September 11th.His difficulty of breathing has increased: the act of expectoration causes great distress: what he brings up is thick mucus.Pulse 82.The emphysema can now be felt all round the chest, over the abdomen, and down the arms.He was ordered a saline mixture, with ipecacuanha wine and chloric ether: and broth for diet.
Abstract 17094: The Curcumin Analogue GO-Y030 Effectively Suppresses Cardiac Hypertrophy and Systolic Dysfunction Through p300-HAT Inhibition
Authors: Kana Shimizu, Masafumi Funamoto, Yoichi Sunagawa, Yasufumi Katanasaka, Yusuke Miyazaki, Mai Genpei, Satoshi Shimizu, Nurmila Sari, Hiroyuki Shibata, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
Journal: Circulation (2018)

Introduction: We previously found that a natural p300 histone acetyltransferase (HAT) inhibitor, curcumin, suppresses the development of heart failure. However, curcumin has low bioavailability; therefore, it is important to find analogues to it to enhance its therapeutic potential. In the present study, we focused on C 5 -curcuminoids, which possess stronger anti-cancer activity than curcumin, and investigated whether they inhibit p300-HAT activity, and therefore whether they may be useful as therapeutic agents for heart failure. Methods &amp; Results: First, an in vitro p300 HAT assay revealed that the IC 50 value of GO-Y030, one of the C 5 -curcumin analogues investigated, was 1.1 μM, while that of curcumin was 9.4 μM. Moreover, the assay revealed that both mono-ketone moiety and 4 alkoxy groups (3, 3’, 5, 5’) were important for the enhancement of p300-HAT inhibition of GO-Y030. Second, cultured cardiomyocytes were treated with GO-Y030 or curcumin and then stimulated with phenylephrine (PE). 1 μM of GO-Y030 suppressed the following effects to the same extent as 10 μM of curcumin: PE-induced histone H3K9 acetylation, increases in the mRNA levels of ANF and BNP, and an increase in the surface area of cardiomyocytes. Third, C57BL/6j male mice were subjected to transverse aortic constriction (TAC) or sham operation. One day after the operation, TAC mice were randomly assigned to five groups: vehicle, 1 or 50 mg/kg curcumin, and 0.1 or 0.5 mg/kg GO-Y030. Oral administrations were repeated for 6 weeks. Echocardiographic analysis showed that 0.5 mg/kg GO-Y030 prevented a TAC-induced increase in posterior wall thickness and systolic dysfunction to the same extent as 50 mg/kg curcumin. Moreover, 0.5 mg/kg GO-Y030 suppressed increases in HW/BW ratio, myocardial cell diameter, perivascular fibrosis, mRNA levels of ANF and BNP, and histone H3K9 acetylation to the same extent as 50 mg/kg curcumin. Conclusions: These results indicate that the curcumin analog GO-Y030 strongly inhibits p300-HAT activity compared to curcumin and its derivatives in vitro , and that a low dose of GO-Y030 prevented both cardiomyocyte hypertrophy and the development of heart failure. These findings suggest that GO-Y030 may be more effective than curcumin for heart failure therapy.
Effect of androgen receptor directed therapy in prostate cancer patients with COVID-19.
Authors: Serhan Unlu, Junghee Jenny Shin, Jennefer Par-Young, Joseph Vinetz, Daniel P. Petrylak, Insoo Kang, Joseph W. Kim
Journal: Journal of Clinical Oncology (2022)

161 Background: TMPRSS2 is one of the two key enzymes that SARS-CoV-2 requires for its entry to the cell. TMPRSS2 is regulated by androgen receptor. It is well described Androgen Receptor Directed Therapy (ARDT) downregulates the expression of TMPRSS2. We hypothesized that the ARDT has a protective role in patients with prostate cancer (PCa) from poor outcome of COVID-19. Methods: A retrospective chart review of PCa patients with COVID-19 between March to October 2020 in the Yale-New Haven Health System was performed. Demographics, comorbidities, home medications, laboratory data, treatment, and clinical outcomes of COVID-19 were collected. ARDT was defined as the use of GnRH agonist, GnRH antagonist, or androgen receptor antagonist. This study was reviewed and approved by the Institutional Review Boards of Yale University. Results: A total of 146 (1.1%) prostate cancer cases were identified from the 13,642 cases of COVID-19. The clinical characteristics are summarized in the table. Twenty-five (17%) were on active ARDT and 121 (83%) not on ARDT (non-ARDT). The rates of hospitalization were the same: 52%, between the ARDT and non-ARDT group. Of those admitted, mean duration of hospitalization were 9.2 days (Range 1-25) and 14.9 days (Range: 2-47) in ARDT and non-ARDT groups, respectively (p=0.14). Rates of hospital stay &gt;30 days were 0% versus 14.3% (9/63) in ARDT and non-ARDT groups, respectively (p=0.15). Intubation rates were 0% versus 11% (7/63) for ARDT and non-ARDT groups, respectively (p=0.21). Mortality rates were 8% and 13.2%, in ARDT and non-ARDT groups, respectively (p=0.47). Conclusions: The prevalence of PCa was infrequent. Despite advanced stage of the cancer in ARDT group, there was a trend toward decreased severity of COVID-19 and mortality rates compared to non-ARDT group. Our data support further investigation on a protective role of hormone therapy in PCa patients with COVID-19.[Table: see text]
Effect of Offering Care Management or Online Dialectical Behavior Therapy Skills Training vs Usual Care on Self-harm Among Adult Outpatients With Suicidal Ideation
Authors: Gregory E. Simon, Susan M. Shortreed, Rebecca C. Rossom, Arne Beck, Gregory N. Clarke, Ursula Whiteside, Julie E. Richards, Robert B. Penfold, Jennifer M. Boggs, Julia Smith
Journal: JAMA (2022)

People at risk of self-harm or suicidal behavior can be accurately identified, but effective prevention will require effective scalable interventions.
Preventive Medicine and Public Health
Authors: William H. Foege
Journal: JAMA (1991)

The key public health stories of 1990 involved the interface of science and politics, but unfortunately these stories do not yet include a solution to the problems of medical access experienced by many people in our country or the health gap between whites and minorities.<sup>1</sup> On September 30, 1990, the heads of state for 71 countries met at the United Nations in New York, NY, at the Summit for Children to discuss child survival and child health. High-level delegations were present from an additional 69 countries. The significance of this health meeting is underscored by the fact that never before have so many leaders from various countries gathered for any reason. Careful background preparations had been made by the health leaders in the countries represented, by the United Nations' agencies, and by work groups of bilateral and multilateral health workers.<sup>2,3</sup> At the end of the day the attendees
QuickStats: Rates* of Emergency Department Visits Related to Mental Health Disorders Among Adults Aged ≥18 Years, by Disorder Category† — National Hospital Ambulatory Medical Care Survey, United States, 2017–2019§
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Anxiety disorders Mood disordersOther MHD Schizophrenia Visits per 1,000 persons MHD categoryAbbreviations: ED = emergency department; MHD = mental health disorder.* Visit rates are based on the July 1, 2017-July 1, 2019, estimates of the civilian, noninstitutionalized population as developed by the U.S. Census Bureau Population Division; 95% CIs are indicated by error bars.† ED visits with diagnosed MHDs were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes F01-F99 and were categorized into the following disorder categories: psychoactive substance use disorders (F10-F19); anxiety, stress-related, or other nonpsychotic mental disorders (F40-F48); mood (affective) disorders (F30-F39); other MHD (F01-F09 or F50-F99); and schizophrenia, schizotypal, delusional, or other nonmood psychotic disorders (F20-F29).A visit could be included in more than one disorder category.§ Based on a sample of visits by adults aged ≥18 years to EDs in noninstitutional general and short-stay hospitals located in the 50 states and the District of Columbia, excluding federal, military, and Veterans Administration hospitals.During 2017-2019, 52.9 ED visits per 1,000 persons were related to a diagnosed MHD in the United States per year.Approximately one half of mental health-related visits had a diagnosis of a psychoactive substance use disorder at a rate of 27.1 visits per 1,000 persons per year, followed by an anxiety, stress-related, or other nonpsychotic mental disorder (14.4), mood (affective) disorder (12.6), other MHD (5.3), and schizophrenia, schizotypal, delusional, or other nonmood psychotic disorder (4.0).
Medicine as constraint: Assessing the barriers to gender-affirming care
Authors: Anish Kumar, Uchechukwu O. Amakiri, Joshua D. Safer
Journal: Cell Reports Medicine (2022)

In this commentary, we describe the way in which science has been used to constrain transgender peoples' access to gender-affirming care. The required diagnosis of gender dysphoria is rooted in both the historical assumption that psychological distress is an inherent aspect of being transgender and the incorrect notion that gender-affirming care is a panacea for the mental health issues that transgender people may experience, regardless of whether these mental health issues are related to their being transgender. We provide recommendations for how to address these barriers to care moving forward.
Abstract 17199: Airway Mucociliary Clearance is Impaired After Infant Congenital Cardiac Surgery
Authors: Phillip S Adams, Timothy Corcoran, Michael Czachowski, Al Saville, Ivy Lin, Yuliya Domnina, Tracy Baust, Omar Khalifa, Maliha Zahid, Joan Sanchez de Toledo, Cecilia W Lo
Journal: Circulation (2018)

Introduction: A link between congenital heart disease and airway ciliary dyskinesia has been identified. Postoperative pulmonary dysfunction is highly prevalent after cardiac surgery and contributes to morbidity, mortality, and healthcare costs. We hypothesized that respiratory mucociliary clearance (MCC) would be impaired in the immediate postoperative period after infant congenital cardiac surgery. Methods: 41 infants from 5-254 days old underwent MCC scans using nebulized technetium-99m sulfur colloid either immediate postoperative or later postoperative periods after congenital cardiac surgery. Physiologic variables and medications at the time of scan were recorded. Results: There was no significant correlation between MCC and age, gender, race or any of the of the physiologic variables, such as temperature, SpO2, or FiO2, at the time of the MCC scan. MCC was lowest on the first 2 postoperative days, increased at days 3-7, and highest beyond postoperative day 7 (Fig1). Fentanyl (p=0.023) and paralytics agents (p=0.018) were significantly associated with lower MCC, while benzodiazepines (p=0.447) and dexmedetomidine (p=0.675) showed no measurable impact (Table 1). Conclusion: We show for the first time, with quantitative measurements, the near absence of infant MCC in the immediate postoperative period after congenital cardiac surgery. This may be exacerbated by opioid exposure, which should be minimized. Our results further suggest sedative alternatives such as benzodiazepines and dexmedetomidine are preferable to help optimize infant airway clearance. This may reduce ICU length of stay and improve outcomes after cardiac surgery.
Neutralizing antibody responses elicited by SARS-CoV-2 mRNA vaccination wane over time and are boosted by breakthrough infection
Authors: John P. Evans, Cong Zeng, Claire Carlin, Gerard Lozanski, Linda J. Saif, Eugene M. Oltz, Richard J. Gumina, Shan-Lu Liu
Journal: Science Translational Medicine (2022)

The waning efficacy of SARS-CoV-2 vaccines, combined with the continued emergence of variants resistant to vaccine-induced immunity, has reignited debate over the need for booster vaccine doses. To address this, we examined the neutralizing antibody response against the spike protein of five major SARS-CoV-2 variants, D614G, Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529), in health care workers (HCWs) vaccinated with SARS-CoV-2 mRNA vaccines. Serum samples were collected before vaccination, 3 weeks after first vaccination, 1 month after second vaccination, and 6 months after second vaccination. Minimal neutralizing antibody titers were detected against Omicron pseudovirus at all four time points, including for most patients who had SARS-CoV-2 breakthrough infections. Neutralizing antibody titers against all other variant spike protein–bearing pseudoviruses declined markedly from 1 to 6 months after the second mRNA vaccine dose, although SARS-CoV-2 infection boosted vaccine responses. In addition, mRNA-1273–vaccinated HCWs exhibited about twofold higher neutralizing antibody titers than BNT162b2-vaccinated HCWs. Together, these results demonstrate possible waning of antibody-mediated protection against SARS-CoV-2 variants that is dependent on prior infection status and the mRNA vaccine received. They also show that the Omicron variant spike protein can almost completely escape from neutralizing antibodies elicited in recipients of only two mRNA vaccine doses.
Haematemesis and melaena.
Authors: P F Jones
Journal: BMJ (1977)

Dr Slater is wrong when he states that "Wright3 estimated that a 1°C rise in tempera- ture will increase the estimated blood alcohol concentration by 6.5o/o."Careful scrutiny of Wright's paper shows that he made no such claim.However, in the same proceedings Dubowski4 stated that "it may be well to point out that each 1°C increase in actual alveolar breath exit temperature between 34°C and 37°C would tend to increase a blood alcohol concentration calculated on the basis of an assumed 1:2100 ratio by about 6 50 over the actual level.
EDITORIAL CORRESPONDENCE.
Authors: None J. H. H.
Journal: JAMA (1890)

Annual Meeting of the American Rhinological Association. <h3>First Day.</h3> The Eighth Annual Meeting of this Association convened at the Gault House in Louisville, October 6, with a full representation of the fellows of the Society. At nine o'clock the records of the previous meeting were presented and approved and other preliminary business considered. At ten o'clock the roll was called and the regular meeting was formally opened with an address by the President, Dr. Arthur G. Hobbs, of Atlanta, Ga. The afternoon session of the first day was occupied in an informal consideration of its purposes, interests and the necessary modifications of its rules to best insure the greatest success of the Association. The leading rhinologists of the country were in attendance, and the discussions controlled the entire session. <h3>Second Day.</h3> The reading of papers being in order the first one was presented by Dr. A. B. Thrasher, of Cincinnati,
Annals Consult Guys - Causes of Green Urine: Redux
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2021)

Web ExclusivesOctober 2021Annals Consult Guys - Causes of Green Urine: ReduxFREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this author and Howard H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W20-0026 CME/MOC SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This episode of Annals Consult Guys addresses an additional cause of green urine that has been identified since they first discussed the case of a patient who developed green urine in the perioperative period.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Disclosures: Geno J. Merli, MD, and Howard H. Weitz, MD, report that they have no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Stephanie Chang, MD, MPH, Deputy Editor, reports employment with the Agency for Healthcare Research and Quality, travel compensation from the Guidelines International Network, and participation in the Patient-Centered Outcomes Research Institute methodology committee. Vineet Chopra, MD, MSc, Deputy Editor, reports grants received from the Agency for Healthcare Research and Quality and royalties from UpToDate and Oxford University Press. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interests to disclose. Eliseo Guallar, MD, MPH, DrPH, Deputy Editor, Statistics, reports that he has no financial relationships or interests to disclose. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center and consultancy with Boston Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports employment with the Perelman School of Medicine, University of Pennsylvania, and consultancies with the U.S. Food and Drug Administration and the State of Colorado. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics October 2021Volume 174, Issue 10Page: CG1 ePublished: 19 October 2021 Issue Published: October 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.Loading ...
Evaluation of ctDNA alterations in mCRPC patients with germline pathogenic mutations.
Authors: Malcolm Light, Ellen B. Jaeger, Sydney Caputo, William Fleming, Charlotte Manogue, Minqi Huang, Isabelle P. Sussman, Alex Lieberman, Patrick Miller, Pedro C. Barata, Jodi Lyn Layton, Brian E. Lewis, Elisa M. Ledet, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2022)

177 Background: Germline alterations are found in approximately 12-17% of CRPC patients. Similarly, evaluating tumoral changes with circulating tumor DNA (ctDNA) has become an increasingly useful tool for understanding mechanisms underpinning disease progression. In this study, we evaluated both germline and somatic genetic changes in patients with mCRPC. Methods: Patients included had germline screening and ctDNA analyzed with the Guardant 360 assay. All patients were CRPC at the time of Guardant testing. Germline alterations were classified as pathogenic/likely-pathogenic or not pathogenic. Only ctDNA alterations with an alleleic fraction greater than 0.5% were included in analyses. Additional evaluation of CRPC status, treatment history, family history and other clinical covariates are ongoing. Chi-square and Fischer’s Exact tests were used for comparison of cohorts. Results: A total of 168 Caucasian CRPC patients had Guardant 360 testing at time of progression and germline testing between 2015-2021. 61% (n = 102/168) of patients have previously had treatment with abiraterone, 49% (n = 82/168) have had Enzalutamide and 40% (n = 68/168) have had treatment with taxanes. 12% (n = 20/168) of CRPC patients had a pathogenic/likely-pathogenic (P/LPv) germline alteration, 46% (n = 77/168) had a germline variant of unknown significance (VUS), 42% (n = 71/168) were germline negative. CRPC patients with pathogenic germline mutations were significantly more likely to have subsequent somatic alterations in BRCA2 (OR = 5.05, 95% C.I. (1.11, 23.01), p = 0.055), NF1 (OR = 7.89, 95% C.I. (2.15, 28.10), p = 0.004), and TP53 (OR = 3.52, 95% C.I. (1.28, 9.68), p = 0.015). In TP53, among germline positive patients, 45% (n = 9/20) had TP53 alterations compared to 30% (n = 45/148) of germline negative patients. Conclusions: Germline positive (P/LPv) CRPC patients were significantly more likely to have somatic alterations in BRCA2, NF1, and TP53. Understanding the totality of genetic changes, both germline and acquired somatic alterations is essential as the arsenal of targeted treatment for CRPC continues to expand. Additional studies including longitudinal assessment genetic changes and clinical correlates will be necessary to evaluate these findings in the context of treatment outcomes and disease progression.
Allergy abstracts
Authors: David Stein, Harold Frledman, Eve&ml Ohio, Monroe Stamford, Cum Eugene, Walzer Bridgeport, N Berger Freehold, Cleveland Stein, Bert Ohio, Tyler Kahn, Tex Andre, Su~em Codispoti, Y Robert, New Lin, Randolph Christopher, Mertinez -Maza
Journal: Journal of Allergy and Clinical Immunology (1987)