Publications by authors named "J Jacobs"

4,350 Publications

  • Page 1 of 1

Refusing blood transfusions from COVID-19-vaccinated donors: are we repeating history?

Br J Haematol 2021 Sep 15. Epub 2021 Sep 15.

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.17842DOI Listing
September 2021

MAD2L2 dimerization and TRIP13 control shieldin activity in DNA repair.

Nat Commun 2021 Sep 14;12(1):5421. Epub 2021 Sep 14.

Division of Oncogenomics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

MAD2L2 (REV7) plays an important role in DNA double-strand break repair. As a member of the shieldin complex, consisting of MAD2L2, SHLD1, SHLD2 and SHLD3, it controls DNA repair pathway choice by counteracting DNA end-resection. Here we investigated the requirements for shieldin complex assembly and activity. Besides a dimerization-surface, HORMA-domain protein MAD2L2 has the extraordinary ability to wrap its C-terminus around SHLD3, likely creating a very stable complex. We show that appropriate function of MAD2L2 within shieldin requires its dimerization, mediated by SHLD2 and accelerating MAD2L2-SHLD3 interaction. Dimerization-defective MAD2L2 impairs shieldin assembly and fails to promote NHEJ. Moreover, MAD2L2 dimerization, along with the presence of SHLD3, allows shieldin to interact with the TRIP13 ATPase, known to drive topological switches in HORMA-domain proteins. We find that appropriate levels of TRIP13 are important for proper shieldin (dis)assembly and activity in DNA repair. Together our data provide important insights in the dependencies for shieldin activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-25724-yDOI Listing
September 2021

Personalized Exercise Programs Based upon Remote Assessment of Motor Fitness: A Pilot Study among Healthy People Aged 65 Years and Older.

Gerontology 2021 Aug 17:1-15. Epub 2021 Aug 17.

Department of Geriatric Rehabilitation, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.

Background: The World Health Organization has recently updated exercise guidelines for people aged >65 years, emphasizing the inclusion of multiple fitness components. However, without adequate recognition of individual differences, these guidelines may be applied using an approach that "one-size-fits-all." Within the shifting paradigm toward an increasingly personalized approach to medicine and health, it is apparent that fitness components display a significant age-related increase in variability. Therefore, it is both logical and necessary to perform an accurate individualized assessment of multiple fitness components prior to optimal prescription for a personalized exercise program.

Objective: The aim of the study was to test the feasibility and effectiveness of a novel tool able to remotely assess balance, flexibility, and strength using smartphone sensors (accelerometer/gyroscope), and subsequently deliver personalized exercise programs via the smartphone.

Methods: We enrolled 52 healthy volunteers (34 females) aged 65+ years, with normal cognition and low fall risk. Baseline data from remote smartphone fitness assessment were analyzed to generate 42 fitness digital markers (DMs), used to guide personalized exercise programs (×5/week for 6 weeks) delivered via smartphone. Programs included graded exercises for upper/lower body, flexibility, strength, and balance (dynamic, static, and vestibular). Participants were retested after 6 weeks.

Results: Average age was 74.7 ± 6.4 years; adherence was 3.6 ± 1.7 exercise sessions/week. Significant improvement for pre-/posttesting was observed for 10/12 DMs of strength/flexibility for upper/lower body (sit-to-stand repetitions/duration; arm-lift duration; torso rotation; and arm extension/flexion). Balance improved significantly for 6/10 measures of tandem stance, with consistent (nonsignificant) trends observed across 20 balance DMs of tandem walk and 1 leg stance. Balance tended to improve among the 37 participants exercising ≥3/week.

Discussion: These preliminary results provide a proof of concept, with high adherence and improved fitness confirming the benefits of remote fitness assessment for guiding home personalized exercise programs among healthy adults aged >65 years. Further examination of the application within a randomized control study is necessary, comparing the personalized exercise program to general guidelines among healthy older adults, as well as specific populations, such as those with frailty, deconditioning, cognitive, or functional impairment. The study tool offers the opportunity to collect big data, including additional variables, with subsequent utilization of artificial intelligence to optimize the personalized exercise program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000517918DOI Listing
August 2021

Small Intestinal Phosphate Absorption: Novel Therapeutic Implications.

Am J Nephrol 2021 Aug 19;52(7):522-530. Epub 2021 Aug 19.

Division of Nephrology and Hypertension, NorthShore University Health System, Evanston, Illinois, USA.

Background: Chronic kidney disease (CKD) affects approximately 15% of adults in the USA. As CKD progresses, urinary phosphate excretion decreases and results in phosphate retention and, eventually, hyperphosphatemia. As hyperphosphatemia is associated with numerous adverse outcomes, including increased cardiovascular mortality, reduction in phosphorus concentrations is a guideline-recommended, established clinical practice. Dietary phosphate restriction, dialysis, and phosphate binders are currently the only options for phosphate management. However, many patients with hyperphosphatemia have phosphorus concentrations >5.5 mg/dL, despite treatment.

Summary: This review pre-sents recent advances in the understanding of intestinal phosphate absorption and therapeutic implications. Dietary phosphate is absorbed in the intestine through two distinct pathways, paracellular absorption and transcellular transport. Recent evidence indicates that the paracellular route accounts for 65-80% of total phosphate absorbed. Thus, the paracellular pathway is the dominant mechanism of phosphate absorption. Tenapanor is a first-in-class, non-phosphate binder that inhibits the sodium-hydrogen exchanger 3 or solute carrier family 9 member 3 (SLC9A3) encoded by the SLC9A3 gene, and blocks paracellular phosphate absorption. Key Messages: Targeted inhibition of sodium-hydrogen exchanger 3 effectively reduces paracellular permeability of phosphate. Novel therapies that target the paracellular pathway may improve phosphate control in chronic kidney disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000518110DOI Listing
August 2021

The impact of climate change and emerging infectious diseases on the blood supply.

Authors:
Jeremy W Jacobs

Transfus Apher Sci 2021 Sep 6:103272. Epub 2021 Sep 6.

Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transci.2021.103272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420088PMC
September 2021
-->