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101.
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103.
13C NMR studies of gluconeogenesis in rat liver cells: Utilization of labeled glycerol by cells from euthyroid and hyperthyroid rats 总被引:6,自引:0,他引:6 下载免费PDF全文
S. M. Cohen S. Ogawa R. G. Shulman 《Proceedings of the National Academy of Sciences of the United States of America》1979,76(4):1603-1607
The gluconeogenic pathway from [2-13C]glycerol and [1,3-13C]glycerol has been followed in suspensions of isolated rat hepatocytes at 25 degrees C by 13C NMR at 90.5 MHz. The flow of label through the major pathway from glycerol to L-glycerol 3-phosphate and into glucose was followed in cells from control and triiodothyronine-treated rats. Treatment increased the rates of glucose formation and glycerol consumption 2-fold and decreased the alphaGP level to 40%. We calculate that approximately 60% of the flux is through the mitochondrial glycerol phosphate dehydrogenase in cells from triiodothyronine-treated rats, compared with approximately 15% in cells from the controls. Equal distribution of label between the trioses of glucose was obtained and, because the C3-C4 spin-spin coupling gives the distribution of labeled carbons in the same molecule, it was possible to measure the amount of triose from unlabeled fructose incorporated into the glucose labeled at carbons 1, 3, 4, and 6. About 10% of the hexoses had flowed through the pentose cycle and back into the hexose pathway in cells from fasted rats. From the distribution of label at glucose carbons not labeled via the major pathway and from the carbon spin-spin splitting patterns observed, we conclude that transketolase is reversible whereas transaldolase is essentially irreversible in the nonoxidative pentose branch. 相似文献
104.
Ofer Beharier Romina Plitman Mayo Tal Raz Kira Nahum Sacks Letizia Schreiber Yael Suissa-Cohen Rony Chen Rachel Gomez-Tolub Eran Hadar Rinat Gabbay-Benziv Yuval Jaffe Moshkovich Tal Biron-Shental Gil Shechter-Maor Sivan Farladansky-Gershnabel Hen Yitzhak Sela Hedi Benyamini-Raischer Nitzan D. Sela Debra Goldman-Wohl Ziv Shulman Ariel Many Haim Barr Simcha Yagel Michal Neeman Michal Kovo 《The Journal of clinical investigation》2021,131(13)
BACKGROUNDThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODSA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTSThe BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSIONAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDINGIsrael Science Foundation and the Weizmann Institute Fondazione Henry Krenter. 相似文献
105.
JD Roberts JC Herkert J Rutberg SM Nikkel ACP Wiesfeld D Dooijes RM Gow JP van Tintelen MH Gollob 《Clinical genetics》2013,83(5):452-456
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis. 相似文献
106.
Connie Marras MD PhD Kelly A. Mills MD Shirley Eberly MS David Oakes PhD Kelvin L. Chou MD PhD Matthew Halverson BA BS Sotirios A. Parashos MD PhD Christopher G. Tarolli MD MHPE Jin-Shei Lai PhD Cindy J. Nowinsky MD PhD Oksana Suchowersky MD Eric S. Farbman MD Lisa M. Shulman MD Tanya Simuni MD 《Movement disorders》2021,36(8):1979-1983
107.
Stephanie R McKeown Paul Hatfield Robin JD Prestwich Richard E Shaffer Roger E Taylor 《The British journal of radiology》2015,88(1056)
Most radiotherapy (RT) involves the use of high doses (>50 Gy) to treat malignant disease. However, low to intermediate doses (approximately 3–50 Gy) can provide effective control of a number of benign conditions, ranging from inflammatory/proliferative disorders (e.g. Dupuytren''s disease, heterotopic ossification, keloid scarring, pigmented villonodular synovitis) to benign tumours (e.g. glomus tumours or juvenile nasopharyngeal angiofibromas). Current use in UK RT departments is very variable. This review identifies those benign diseases for which RT provides good control of symptoms with, for the most part, minimal side effects. However, exposure to radiation has the potential to cause a radiation-induced cancer (RIC) many years after treatment. The evidence for the magnitude of this risk comes from many disparate sources and is constrained by the small number of long-term studies in relevant clinical cohorts. This review considers the types of evidence available, i.e. theoretical models, phantom studies, epidemiological studies, long-term follow-up of cancer patients and those treated for benign disease, although many of the latter data pertain to treatments that are no longer used. Informative studies are summarized and considered in relation to the potential for development of a RIC in a range of key tissues (skin, brain etc.). Overall, the evidence suggests that the risks of cancer following RT for benign disease for currently advised protocols are small, especially in older patients. However, the balance of risk vs benefit needs to be considered in younger adults and especially if RT is being considered in adolescents or children. 相似文献
108.
Long‐term effectiveness of recommended boosted protease inhibitor‐based antiretroviral therapy in Europe 下载免费PDF全文
JR Santos A Cozzi‐Lepri A Phillips S De Wit C Pedersen P Reiss A Blaxhult A Lazzarin M Sluzhynska C Orkin C Duvivier J Bogner P Gargalianos‐Kakolyris P Schmid G Hassoun I Khromova M Beniowski V Hadziosmanovic D Sedlacek R Paredes JD Lundgren 《HIV medicine》2018,19(5):324-338
Objectives
The aim of the study was to evaluate the long‐term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)‐, darunavir/ritonavir (DRV/r)‐, and lopinavir/ritonavir (LPV/r)‐containing regimens.Methods
Data were analysed for 5678 EuroSIDA‐enrolled patients starting a DRV/r‐, ATZ/r‐ or LPV/r‐containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART‐naïve subjects (8%) at ritonavir‐boosted protease inhibitor (PI/r) initiation; (2) ART‐experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV‐1 RNA copies/mL; and (3) ART‐experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan–Meier and multivariable Cox models were used to compare risks of failure by PI/r‐based regimen. The main analysis was performed with intention‐to‐treat (ITT) ignoring treatment switches.Results
The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log‐rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART‐naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment‐experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r‐based ART.Conclusions
Although confounding by indication and calendar year cannot be completely ruled out, in ART‐experienced subjects the long‐term effectiveness of DRV/r‐containing regimens appears to be greater than that of ATZ/r and LPV/r.109.
110.
Geriatric Care Boot Camp: An Interprofessional Education Program for Healthcare Professionals 下载免费PDF全文
Lauren B. Solberg JD Laurence M. Solberg MD AGSF Christy S. Carter PhD 《Journal of the American Geriatrics Society》2015,63(5):997-1001
In response to the need for interprofessional geriatrics education, a half‐day geriatric care boot camp for healthcare professionals was held that covered core concepts in geriatric medicine: delirium and dementia, medication management, palliative care, ethics, and a general overview of older adults. Aspects of the curriculum focused on interprofessional education, and the attendees and presenters were healthcare professionals from a wide variety of fields. Primary objectives were to determine changes in knowledge of core concepts in geriatrics and level of comfort in caring for older adults. Secondary objectives assessed whether participants found the interprofessional approach beneficial and whether they used or shared this information with others in their professional activities. Participants completed pre‐ and postassessment surveys. Changes in participant understanding of each core concept were statistically significant, as was the change in comfort level of participants in caring for older adults. Furthermore, attendees found the multidisciplinary perspective of the boot camp beneficial. A 3‐month follow‐up survey assessed whether attendees applied and shared information learned in their own professional activities. Half of the respondents who reported sharing universally shared core concepts. Delirium and dementia information was most frequently shared. Information was most frequently shared with students, nurses, and patients’ families. Attendees less frequently shared, or did not share, with physicians, physician assistants, social workers, physical and occupational therapists, nutritionists, and dentists. The healthcare professionals who may benefit greatly from future education programs are those with whom the boot camp information was least frequently shared; thus, they are appropriate targets for advertisements for future programs. 相似文献