scholarly journals A Validation Study on Immunophenotypic Differences in T-lymphocyte Chromosomal Radiosensitivity between Newborns and Adults in South Africa

Radiation ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 1-16
Author(s):  
Monique Engelbrecht ◽  
Roya Ndimba ◽  
Xanthene Miles ◽  
Shankari Nair ◽  
Matthys Hendrik Botha ◽  
...  

Children have an increased risk of developing radiation-induced secondary malignancies compared to adults, due to their high radiosensitivity and longer life expectancy. In contrast to the epidemiological evidence, there is only a handful of radiobiology studies which investigate the difference in radiosensitivity between children and adults at a cellular level. In this study, the previous results on the potential age dependency in chromosomal radiosensitivity were validated again by means of the cytokinesis-block micronucleus (CBMN) assay in T-lymphocytes isolated from the umbilical cord and adult peripheral blood of a South African population. The isolated cells were irradiated with 60Co γ-rays at doses ranging from 0.5 Gy to 4 Gy. Increased radiosensitivities of 34%, 42%, 29%, 26% and 16% were observed for newborns compared to adults at 0.5, 1, 2, 3 and 4 Gy, respectively. An immunophenotypic evaluation with flow cytometry revealed a significant change in the fraction of naïve (CD45RA+) T-lymphocytes in CD4+ and CD8+ T-lymphocytes with age. Newborns co-expressed an average of 91.05% CD45RA+ (range: 80.80–98.40%) of their CD4+ cells, while this fraction decreased to an average of 39.08% (range: 12.70–58.90%) for adults. Similar observations were made for CD8+ cells. This agrees with previous published results that the observed differences in chromosomal radiosensitivity between newborn and adult T-lymphocytes could potentially be linked to their immunophenotypic profiles.

2019 ◽  
Author(s):  
Nestoras Mathioudakis ◽  
Estelle Everett ◽  
Noora Al-Hajri ◽  
Mohammed Abusamaan ◽  
Clare Lee ◽  
...  

BACKGROUND About one-third of American adults have prediabetes and are at increased risk of type 2 diabetes. Mobile health (mHealth) technologies provide a scalable approach to diabetes prevention by encouraging physical activity (PA), weight loss, and adherence to a healthy diet in large numbers of patients. OBJECTIVE To identify factors associated with improvements in PA and glycated hemoglobin (A1c) measures among prediabetic adults who received a mobile intervention program (smartphone app in combination with a digital body weight scale) in a previously completed pilot study. METHODS We conducted a post hoc analysis of a 3-month prospective, single-arm, observational study using the Sweetch™ mHealth intervention among adults with prediabetes. Change in A1C was calculated as the difference between the 3-month and baseline A1C measurements and was categorized as decrease vs. no decrease. PA was evaluated using the total minutes and metabolic equivalent of task (MET)-hours per week. Change in MET-hours/week was categorized as increase vs. no increase. Age, sex, race, education, employment status, area deprivation, smartphone usage attitudes, and PA stage of change were compared between groups by outcomes of change in A1C and change in MET-hour/week. RESULTS A total of 37 adults received the final Sweetch mobile intervention and were included in the analysis. 62% were female and 81% were white, with average age of 57 years. The median [IQR] baseline A1C was 6.0% [5.8, 6.2]. A1C measure at 3-month was decreased in 24 (65%) participants when compared to baseline A1C. There was an inverse association between average MET-hours per week and change in A1C. Among participants whose A1C decreased vs. did not decrease, the MET-hours per week in last 2 weeks of study was 18.7 (8.4) and 15.0 (7.1), respectively (P=0.19), and the change in MET-hours per week was 2.1 (7.1) and 4.1(6.1), respectively (P=0.41). There were otherwise no statistically significant differences in participant factors by A1C and PA outcomes. CONCLUSIONS In this small pilot study, Sweetch mHealth intervention achieved comparable A1C response prediabetic adults with different individual, sociodemographic and anthropometric characteristics. CLINICALTRIAL ClincialTrials.gov NCT02896010; https://clinicaltrials.gov/ct2/show/NCT02896010 (Archived by WebCite at http://www.webcitation.org/6xJYxrgse)


2017 ◽  
Vol 72 ◽  
pp. S153-S154
Author(s):  
P. Maingon ◽  
C. Mirjolet ◽  
G. Truc ◽  
P.C. Karine ◽  
G. Nöel ◽  
...  

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A136-A136
Author(s):  
S Brooks ◽  
R G J A Zuiker ◽  
G E Jacobs ◽  
I Kezic ◽  
A Savitz ◽  
...  

Abstract Introduction Seltorexant (JNJ-42847922), a potent and selective antagonist of the human orexin-2 receptor, is being developed for the treatment of major depressive disorder. Seltorexant also has sleep-promoting properties. Investigating the effects of sleep-promoting medications on driving is important because some of these agents (e.g. GABAA receptor agonists) may be associated with increased risk of motor vehicle accidents. We evaluated the effect of seltorexant on driving after forced awakening at night, using a validated driving simulator. Methods This double-blind, placebo and active-controlled, randomized, 3-way cross-over study was conducted in 18 male and 18 female healthy subjects. All subjects received seltorexant 40 mg, zolpidem 10 mg, or placebo 15 minutes before bedtime. Eighteen subjects were awakened at 2- and 6-hours post-dose, and the other 18 at 4- and 8-hours post-dose. At those timepoints, pharmacokinetics, objective (standard deviation of the lateral position [SDLP]) and subjective effects (using Perceived Driving Quality and Effort Scales) on driving ability, postural stability and subjective sleepiness were assessed. Results For seltorexant, the SDLP difference from placebo (95% confidence interval) at 2-, 4-, 6- and 8-hours post-dose was 3.9 cm (1.26, 6.60), 0.9 cm (-1.08, 2.92), 1.1 cm (-0.42, 2.63), and 0.6 cm (-2.75, 1.55), respectively vs. 9.6 cm (6.97, 12.38), 6.6 cm (3.53, 9.60), 4.7 cm (1.46, 7.85), and 1.3cm (-1.16, 3.80), respectively for zolpidem. The difference from placebo was significant at 2-hours after taking seltorexant, while the difference from placebo was significant at 2, 4 and 6-hours after zolpidem. Subjective driving quality was decreased for both drugs at all time points and driving effort was increased up to 4-hours post-dose for both medications. Subjective sleepiness showed a significant increase compared to placebo 2- and 4-hours after administration of either drug. Postural stability was decreased up to 2-hours after administration of seltorexant, and up to 4-hours after administration of zolpidem. Conclusion Compared to zolpidem, objective effects on driving performance were more transient after seltorexant administration and largely normalized by 4–6 hours post-dose. Support (if any) This work was sponsored by Janssen R&D.


2021 ◽  
pp. 513-518
Author(s):  
Samragnyi Madala ◽  
Abhishek Polavarapu ◽  
Dhineshreddy Gurala ◽  
Vivek Gumaste

We commonly see patients presenting with either portal hypertensive gastropathy (PHG) or radiation gastritis. Radiation-induced hemorrhagic gastritis is an unusual lethal complication postradiation. Patients with preexisting PHG have very friable mucosa that can easily bleed after radiation for cancer treatment. There is an increased risk of bleeding with both entities present together. Our aim is to focus on treatment and possible prevention of gastrointestinal bleeding in patients with preexisting PHG undergoing radiation therapy for newly diagnosed cancer. Several therapies like prednisolone, argon plasma coagulation, laser coagulation have been proposed. There are no set guidelines for treatment. In these patients, if radiation therapy is indicated either for hepatic or gastrointestinal malignancy, it is suggested to premedicate with proton pump inhibitors or sucralfate. We describe a case of 73-year-old female who presented with upper gastrointestinal bleeding. She had liver cirrhosis secondary to nonalcoholic fatty liver disease and diagnosed with pancreatic cancer, for which she received chemoradiation. She was found to have both radiation gastritis and PHG with diffuse erythematous, edematous, congested mucosa with diffuse oozing blood in the antrum making it very challenging to treat.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hetti von Hellens ◽  
Leea Keski-Nisula ◽  
Heidi Sahlman

Abstract Background The maternal use of paracetamol during pregnancy has been associated with the development of preeclampsia. This study aims to clarify whether the connection is causal or whether it is due to reverse causation. Methods This study is a continuation of the retrospective case cohort study examining 2,508 pregnant women using a variety of drugs and the development of preeclampsia (1,252 women with preeclampsia and 1,256 controls). For the purposes of this study, more precise data was collected from several hospital databases of the women among this cohort who had reported taking paracetamol during pregnancy (indications, gestational period etc.); this was evaluated in association with the development of preeclampsia. Results 5.5% (100 cases and 37 controls) of all the study population (2,508) had clearly reported paracetamol use. Women with preeclampsia had used significantly more often paracetamol during pregnancy compared to controls (cases 8.0%, controls 2.9%, p < 0.001). The difference was most evident in the third trimester (after the 29th GW) and the use of paracetamol was associated with both mild and severe preeclampsia. Headache and “general pain” were the most common indications for medication among all paracetamol users. Conclusions The use of paracetamol in the third trimester of pregnancy was associated with preeclampsia. This observation indicates that association between paracetamol use and preeclampsia is probably due to reverse causation, i.e. women with preeclampsia experience more headaches due to preeclampsia symptoms since this association was not detected with the use of paracetamol in earlier stages of pregnancy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.


2021 ◽  
Vol 50 (Supplement_1) ◽  
pp. i12-i42
Author(s):  
E Spurring ◽  
G Donnelly

Abstract Intro In July 2019 the MHRA issued a drug safety update reminding healthcare professionals that rivaroxaban should be taken with food. This came after they received a number of thromboembolic events reported in patients prescribed rivaroxaban, thought to be linked with incorrect ingestion on an empty stomach [1]. Our aim was to establish if the healthcare professionals in our department had this knowledge and to audit our current dispensing practice to assess if our hospitalised patient cohort were being exposed to any increased risk. Methods A retrospective study was conducted using electronic data from 21 patients that were prescribed rivaroxaban across 14 medical wards. A questionnaire was used to establish the staff’s knowledge. Results Of the surveyed healthcare professionals, 79% knew that rivaroxaban should be taken with food (86% of nurses and 79% of doctors). Despite this only 17% of patients took the tablet with food. 75% of patients had rivaroxaban incorrectly dispensed over an hour post meal and 8% were uncertain due to poor documentation. Only 14% of healthcare professionals were aware that in those with swallowing difficulties, rivaroxaban can be crushed. Conclusions In our department most of the healthcare professionals had a good academic knowledge of correct rivaroxaban administration, however we have demonstrated that this is failing to correctly influence clinical practice. 75% of patients taking Rivaroxaban in hospital are being subjected to increased risk due to the hospital environment. This was found to relate to the difference in timing of the drug dispensing round in comparison to meal times. As part of the roll out of electronic prescribing in our trust, a warning now shows when both prescribing and dispensing Rivaroxaban to attempt to improve this highlighted risk. We have also highlighted this to the ward managers and at our governance meeting. Reference 1. Drug Safety Update volume 12, issue 12: July 2019: 3.


2018 ◽  
Vol 47 (1-3) ◽  
pp. 230-235 ◽  
Author(s):  
Frank M. van der Sande ◽  
Karlien J.A. ter Meulen ◽  
Peter Kotanko ◽  
Jeroen P. Kooman

Background: Calcium (Ca) is an essential element that plays a critical role in many biological processes. In dialysis patients, the regulation of Ca balance is highly complex, given the absence of kidney function, endocrine disturbances and the use of drugs such as phosphate binders, vitamin D analogues, and calcimimetics. Also, the use of different dialysate Ca (DCa) baths has profound effect on Ca balance, which depends both on the difference between the Ca concentration in the bath and the serum of the patients, as on the ultrafiltration volume. Summary: The choice of DCa may have important short- and long-term consequences. While lower DCa (especially < 2.5 mEq/L) concentrations have been associated with an increased risk of sudden cardiac death in observational studies, DCa in the higher ranges (3.0 mEq/L and above) may contribute to vascular pathology. Intra-dialytic hemodynamics may also be affected by the choice of DCa. In general, lower DCa concentrations are associated with an increase, and higher DCa concentrations with a decrease in parathyroid hormone (PTH) levels. Preliminary data has suggested that a DCa of 2.75 mEq/L may help in obtaining a net zero intradialytic Ca balance in individual patients, but clinical experience is still limited. Key Message: The optimal Ca balance depends on multiple parameters including blood Ca levels, PTH and the use of phosphate binders and vitamin D analogues, as well as on the risk of hemodynamic stability and cardiac arrhythmias. Therefore, DCa prescription should be individualised. A DCa of 2.75 mEq/L may be useful adjunct for dialysis providers.


Sign in / Sign up

Export Citation Format

Share Document