Introduction: The aim of this study was to investigate the variance components in TP53 mRNA expression after in vivo exposure to double threshold dose of ultraviolet radiation B (UVR-B).
Methods: Twelve six-week-old female albino Sprague-Dawley rats were exposed to double threshold dose (8 kJ/m2) of UVR-B unilaterally and sacrificed at 1, 3, 8, and 24 h after exposure. Lenses were enucleated, and TP53 mRNA expression was detected by qRT-PCR. Variance components for groups, animals, and measurements were estimated with analysis of variance.
Results: The variance for groups is 0.15 rel.2. The variance for animals is 0.29 rel.2. The variance for measurements is 0.32 rel.2.
Conclusion: The variance for animals is in the same order as the variance for measurements. The reduction of the variance for measurements is needed in order to obtain the acceptable level of detection of the difference in TP53 mRNA expression and the reduction in sample size.
Introduction: Physical inactivity has been linked to various noncommunicable diseases and their related health problems. As primary health care physicians (PHCPs) play a crucial role in promoting health and preventing disease, this study aims to determine the extent of physical inactivity among PHCPs and its impact on their counseling practices.
Methods: A cross-sectional study was conducted across all primary health care centers in Qatar, targeting 511 physicians. A modified self-administered WHO stepwise tool was used to measure physical activity (PA) with another questionnaire to assess the counseling practices among PHCPs.
Results: Out of 511 physicians, 306 (59.9%) responded to the survey. The majority of the participants were male (58.1%) with an average age of 45.8 ± 7.9 years. The majority of PHCPs were from the UK (44.3%), while only 4.1% were Qatari. Family physician consultants made up 51% of the respondents, while 30.2% were general practitioners, and the average years of experience were 14 ± 8.3 years. Only 39.5% of the respondents met the WHO PA recommendations. 50.5% of the physicians were overweight, and 23.1% were obese. The median percentage of patients counseled about PA was only 60 [IQR: 40-80]%, and there was no link found between a physician's PA level and the percentage of patients they counseled on the subject.
Conclusion: Physicians reported a high prevalence of physical inactivity. Furthermore, the practice of counseling the public on PA was low. Interventions are needed inside and outside the workplace to improve the PA among PHCPs and their counseling practices.
We describe the clinical course of 4 infants infected with severe acute respiratory syndrome coronavirus 2. All were admitted to our tertiary care neonatal intensive care unit during the Omicron variant wave in our region. All 4 infants, who were less than 3 months of age, including three born prematurely, presented with critical illness. However, their clinical presentation varied considerably. Of them, two infants presented with apnea, one with respiratory distress, and one with gastrointestinal manifestation. Our experience with these four infants provides evidence for a severe form of disease and varied clinical presentation in neonates and young infants speculated to be infected with Omicron variant.
Introduction: A new class of nondiffractive, wavefront-shaping Enhanced-Depth-of-Focus (EDoF) IOLs has been introduced very recently to cope with photic phenomena known from diffractive EDoF IOLs. We investigated the through focus modulation transfer function (MTF) of two wavefront-shaping EDoF IOLs compared to an established diffractive EDoF IOL on the optical bench. Such comparison on the optical bench had not been performed before and is of high clinical importance for the cataract surgeon.
Material and methods: Tecnis Symfony (diffractive) and the wavefront-shaping Acrysof IQ Vivity and LuxSmart Crystal IOLs (22 D each) were assessed by the OptiSpheric IOL PRO 2 imaging test bench with an ISO-2 cornea and a wavelength of 546 nm. Apertures of 3 mm and 4.5 mm were applied.
Results: For all three IOLs, two peaks showed up in the through focus MTF curves representing the primary and secondary focus. For Symfony, these peaks were most distinct. Power difference between far and intermediate focus was 1.25 D (Symfony), 1.75 D (Vivity), and 1.5 D (LuxSmart) with an aperture of 3 mm. With an aperture of 4.5 mm, only for LuxSmart, power difference diminished slightly to about 1 D, and only the MTF in the intermediate focus decreased for all lenses.
Conclusion: For all three IOLs, we could confirm a considerable depth of focus that was most extended for Vivity. Both new wavefront-shaping IOLs had lower values of peak MTF but a markedly more continuous through focus behavior compared to the diffractive EDoF IOL.
Introduction: The quest for small molecule inhibitors of the PD-1/PD-L1 checkpoint continues in parallel to the extensive development of monoclonal antibodies directed against this immune checkpoint. Drug screening strategies are being set up to identify novel PD-L1 inhibitors.
Methods: A virtual screening based on molecular docking with the PD-L1 protein dimer has been performed to identify a new binder. Binding of the identified ligand to PD-L1 has been validated experimentally using a microscale thermophoresis (MST) assay. The cellular effect of the compound was evidenced using a fluorescence resonance energy transfer (FRET) assay based on activation of tyrosine phosphatase SHP-2.
Results: We have identified the potent Wnt/β-catenin inhibitor KYA1797K as a weak PD-L1 binder. Molecular docking suggested that the compound can bind to the interface of a PD-L1 dimer, with a geometry superimposable to that of the reference PD-L1 inhibitor BMS-202. The atypical 2-thioxo-4-thiazolidinone motif of KYA1797K, derived from the natural product rhodanine, plays a major role in the interaction with PD-L1. Binding of KYA1797K to recombinant hPD-L1 was validated experimentally, using MST. The drug was found to bind modestly but effectively to hPD-L1. The FRET assay confirmed the weak capacity of KYA1797K to interfere with the activation of SHP-2 upon its interaction with human PD-1.
Discussion: Collectively, the data show that KYA1797K could function as a weak modulator of the PD-1/PD-L1 checkpoint. This effect may contribute, at least partially, to the reported capacity of the β-catenin inhibitor to downregulate PD-L1 in cancer cells. The work also underlines the interest to further consider the rhodanine moiety as a chemical motif for the design of new PD-L1 binders.
Bronchoscopic lung volume reduction (BLVR) for emphysematous hyperinflation has evolved during the last two decades as an alternative to lung volume reduction surgery (LVRS) with lower morbidity and mortality. Emphysematous lung sealant (ELS) is a form of BLVR specifically aimed at patients with collateral ventilation (CV), shown to have favorable outcomes in lung function up to two years. This case series presents four emphysema patients treated bilaterally with ELS, with a follow-up period up to six years. Two of the patients had previously undergone LVRS and BLVR with valves. Following ELS installment, all patients showed positive changes in spirometric values, with varying durability between one and five years. Three patients reported an overall improvement in subjective symptoms after treatment as measured by the COPD Assessment Test (CAT), one of which had lasting improvement even after five years (CAT from 20 to 13). Two of the four treated patients suffered recurrent respiratory exacerbations and pneumonias requiring hospitalization. They both went on to receive lung transplantation within one and three years. This report concludes that ELS has a meaningful effect on reducing hyperinflation in emphysema with improving pulmonary function tests, and relieving symptoms of dyspnea for up to five years. Unfortunately, some patients develop complications leading to recurrent exacerbations. We were not able to show a survival benefit with ELS treatment. This article highlights the need for further research in order to predict who will benefit from this treatment and how to handle CV-positive patients.
Fetal subdural hematoma is an antenatal finding associated with significant morbidity and mortality. It can occur due to maternal or fetal risk factors, and its management varies based on the underlying cause and the anticipated long-term outcomes. We present a case of warfarin-associated fetal subdural hematoma resulting in a live birth and severe neurodevelopmental delay by 10 years of age. In conclusion, counseling regarding the risk of fetal intracranial hemorrhage and the potential neurodevelopmental delay is essential in women who require anticoagulation with warfarin. In addition, close antenatal follow-up with fetal sonography and strict INR monitoring are essential preventative measures.
Introduction: Extremely premature (EP) infants (<28 weeks gestational age) with respiratory conditions after discharge from the neonatal intensive care unit (NICU) impose a significant burden on caregivers. This study explored caregiver burden post-NICU discharge and perceptions of meaningful change in infant chronic respiratory morbidity.
Methods: Adult primary caregivers of EP infants 3-14 months corrected age were recruited through patient advocacy organizations or hospital centers in the USA, Northern Ireland, Germany, and Japan and interviewed by phone. Interviews explored caregiver experiences with infants with respiratory conditions, associated treatment burden, and meaningful change in infant respiratory morbidity as measured by treatment use. Qualitative analysis of interview data was performed using MAXQDA software. Sociodemographic data were summarized using descriptive statistics.
Results: Forty-five caregivers (95.6% female) of EP infants were interviewed. Respiratory morbidities post-NICU discharge included coughing (78%), breathing difficulties (76%), wheezing (58%), and bronchopulmonary dysplasia/chronic lung disease of prematurity (56%). Respiratory medications were required by 87% of infants, 80% used home respiratory technology support (e.g., supplemental oxygen), 38% were re-hospitalized, and 33% had emergency department visits. Caregivers considered visits to the emergency department to be the most burdensome treatment requirement they experienced, and reduction in the number of emergency department visits was considered the most meaningful change in treatment use.
Conclusion: These findings underscore the significant burden faced by caregivers of EP infants with respiratory morbidities. Development of treatments for respiratory complications should take into consideration the concerns and preferences of caregivers in order to provide a meaningful benefit.
Introduction: Various pharmacological treatments are available for preterm infants with patent ductus arteriosus (PDA), but their risks and benefits are controversial. This study aimed to identify the best treatment for PDA using network meta-analysis (NMA) and risk-benefit assessment (RBA).
Methods: Relevant randomized controlled trials (RCTs) were identified from MEDLINE, Scopus, and the Cochrane Library. RCTs were eligible if they were studied for preterm or low birth weight infants with presymptomatic PDA and hemodynamically significant PDA (hsPDA). The outcomes were PDA closure for a benefit and the composite risk outcome of adverse effects (AEs) for risk. An NMA was used to estimate the treatment effects of benefit and risk. The RBA helped to incorporate the risk and benefits of multiple treatments. Then, an incremental risk-benefit ratio was calculated by dividing the incremental risk by benefit using data from NMA, and they were jointly simulated using Monte Carlo methods. Finally, net clinical benefit (NCB) probability curves were constructed at varying acceptability thresholds.
Results: Seventy RCTs with hsPDA were eligible considering 13 different interventions, but data on presymptomatic PDA were not enough for pooling. The clustered ranking plot from NMA indicated that 3 interventions (i.e., high-dose oral ibuprofen, standard-dose oral acetaminophen, and standard-dose oral ibuprofen) yielded high PDA closure and low AE. These three treatments and additional commonly used indomethacin were considered in the RBA. Given an acceptable threshold of 25% or having one AE out of four PDA closures, high-dose oral ibuprofen had a 36% chance of having the highest NCB, followed by standard-dose oral acetaminophen (27%), and oral ibuprofen (23.7%). Subgroup analysis indicated that the chances of having the highest NCB of GA ≥28 weeks were similar to that of all available studies. The best for GA <28 weeks, no data for high-dose oral ibuprofen, was standard-dose oral acetaminophen, followed by standard-dose oral ibuprofen.
Conclusions: Trade-off RBA indicated that high-dose oral ibuprofen might be the best treatment for preterm, GA ≥28 weeks, with hsPDA followed by the standard-dose oral acetaminophen and ibuprofen. Preferably, optimal high doses, postnatal age to start treatment, and long-term outcomes are needed to study in the future.
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