Novel imidazolone derivatives as potential dual inhibitors of checkpoint kinases 1 and 2: Design, synthesis, cytotoxicity evaluation, and mechanistic insights.

Applying various drug design strategies including ring variation, substituents variation, and ring fusion, two series of 2-(alkylthio)-5-(arylidene/heteroarylidene)imidazolones and imidazo[1,2-a]thieno[2,3-d]pyrimidines were designed and prepared as dual potential Chk1 and Chk2 inhibitors. The newly synthesized hybrids were screened in NCI 60 cell line panel where the most active derivatives 4b, d-f, and 6a were further estimated for their five dose antiproliferative activity against the most sensitive tumor cells including breast MCF-7 and MDA-MB-468 and non-small cell lung cancer EKVX as well as normal WI-38 cell. Noticeably, increasing the carbon chain attached to thiol moiety at C-2 of imidazolone scaffold elevated the cytotoxic activity. Hence, compounds 4e and 4f, containing S-butyl fragment, exhibited the most antiproliferative activity against the tested cells where 4f showed extremely potent selectivity toward them. As well, compound 6a, containing imidazothienopyrimidine core, exerted significant cytotoxic activity and selectivity toward the examined cells. The mechanistic investigation of the most active cytotoxic analogs was achieved through the evaluation of their inhibitory activity against Chk1 and Chk2. Results revealed that 4f displayed potent dual inhibition of both Chk1 and Chk2 with IC50 equal 0.137 and 0.25 µM, respectively. It also promoted its antiproliferative and Chk suppression activity via EKVX cell cycle arrest at S phase through stimulating the apoptotic approach. The apoptosis induction was also emphasized by elevating the expression of Caspase-3 and Bax, that are accompanied by Bcl-2 diminution. The in silico molecular docking and ADMET profiles of the most active analogs have been carried out to evaluate their potential as significant anticancer drug candidates.

Epinephrine vs. phenylephrine infusion for prophylaxis against maternal hypotension after spinal anesthesia for cesarean delivery: a randomized controlled trial.

BACKGROUND: The hemodynamic effects of relatively low-dose epinephrine and phenylephrine infusions during cesarean delivery under spinal anesthesia were compared. METHODS: This randomized controlled trial included full-term pregnant women who underwent elective cesarean delivery. After spinal anesthesia, participants received either epinephrine (0.03 mcg/kg/min) or phenylephrine (0.4 mcg/kg/min) infusion that continued until 5 min after delivery. The primary outcome was a composite outcome of the occurrence of any of hypotension, hypertension, bradycardia, and/or tachycardia. Neonatal outcomes, including umbilical artery blood gas and Apgar scores, were assessed. RESULTS: In total, 98 patients in each group were analyzed, and the number of patients with the composite outcome was comparable between the epinephrine and phenylephrine groups (30/98 [31%] vs. 31/98 [32%], respectively; P = 0.877). However, the incidence of hypotension was likely lower in the epinephrine group than in the phenylephrine group (P = 0.066), and the number of hypotensive episodes per patient was lower in the epinephrine group than in the phenylephrine group. On the other hand, the incidence of tachycardia was higher in the epinephrine group than that in the phenylephrine group. The incidence of hypertension was comparable between the two groups and none of the participants developed bradycardia. Neonatal outcomes were comparable between the two groups. CONCLUSIONS: Epinephrine and phenylephrine infusion produced comparable maternal hemodynamics and neonatal outcomes. Epinephrine was associated with a higher incidence of maternal tachycardia and likely lower incidence of maternal hypotension than phenylephrine. IRB number: MD-245-2022. CLINICAL TRIAL REGISTRATION: This study was registered on May 31, 2023 at clinicaltrials.gov registry, NCT05881915, URL: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05881915term=NCT05881915&draw=2&rank=1.

Prevalence and Correlates of Food and/or Housing Instability among Men and Women Post-9/11 US Veterans.

Food and/or housing instability (FHI) has been minimally examined in post-9/11 US veterans. A randomly selected nationally representative sample of men and women veterans (n = 38,633) from the post-9/11 US veteran population were mailed invitation letters to complete a survey on health and well-being. Principal component analysis and multivariable logistic regression were used to identify FHI's key constructs and correlates for 15,166 men and women respondents (9524 men, 5642 women). One-third of veterans reported FHI; it was significantly more likely among women than men (crude odds ratio = 1.31, 95% CI:1.21-1.41) and most prevalent post-service (64.2%). "Mental Health/Stress/Trauma", "Physical Health", and "Substance Use" were FHI's major constructs. In both sexes, significant adjusted associations (p < 0.01) were found between FHI and homelessness, depression, adverse childhood experiences, low social support, being enlisted, being non-deployed, living with seriously ill/disabled person(s), and living in dangerous neighborhoods. In men only, posttraumatic stress disorder (adjusted odds ratio (AOR) = 1.37, 95% CI:1.14-1.64), cholesterol level (elevated versus normal, AOR = 0.79, 95% CI:0.67-0.92), hypertension (AOR = 1.25, 95% CI:1.07-1.47), and illegal/street drug use (AOR = 1.28, 95% CI:1.10-1.49) were significant (p < 0.01). In women only, morbid obesity (AOR = 1.90, 95%CI:1.05-3.42) and diabetes (AOR = 1.53, 95% CI:1.06-2.20) were significant (p < 0.05). Interventions are needed that jointly target adverse food and housing, especially for post-9/11 veteran women and enlisted personnel.

Transcatheter aortic valve implantation with and without mitral stenosis - A national readmission database study.

INTRODUCTION: Mitral valve stenosis (MS) can be concomitantly present in patients undergoing Transcatheter Aortic Valve Implantation (TAVI). Some studies have reported up to one-fifth of patients who underwent TAVI also have MS. The relationship between mitral stenosis and TAVI has led to concerns regarding increased adverse cardiac outcomes during and after the procedure. METHODS: The Nationwide Readmission Database (NRD 2016-2019) was utilized to identify TAVI patients with MS with ICD-10-CM codes. The primary outcome was a 30-day readmission rate. Secondary outcomes included predictors of all-cause readmissions, length of stay, and total hospitalization cost. We assessed readmission frequency with a national sample weighed at 30 days following the index TAVI procedure. Unadjusted and adjusted odds ratios were analyzed for in-hospital outcomes using univariate and multivariate logistic regression for study cohorts. RESULTS: A total of 217,147 patients underwent TAVI procedures during the queried time period of the study. Of these patients, 2140 (0.98 %) had MS. The overall 30-day all-cause readmission rate for the study cohort was 12.4 %. TAVI patients with MS had higher rates of 30-day readmissions (15.8 % vs 12.3 %, aOR 1.22, CI: 1.03-1.45, P < 0.01). Additionally, TAVI patients with MS had longer lengths of hospital stay during index admissions (5.7 vs. 4.3 days), along with higher total hospitalization costs ($55,157 vs. $50,239). In contrast, in-hospital mortality during index TAVI admission did not differ significantly between the two groups, although there was a trend toward higher mortality in the MS group (2.1 % vs. 1.5 %). Among the TAVI MS cohort, patients admitted on weekends (aOR: 1.11, 95 % CI: 1.02-1.22, P = 0.01), admitted to non-metropolitan hospitals (aOR: 1.29, 95 % CI: 1.11-1.66, P = 0.04) and presence of co-morbidities such as atrial fibrillation (AF)/flutter (aOR: 1.24, 95 % CI: 1.16-1.32, P < 0.01), chronic obstructive pulmonary disease (COPD) (aOR: 1.16, 95 % CI: 1.11-1.22, P < 0.01), prior stroke (aOR: 1.09, 95 % CI: 1.03-1.14, P < 0.01), chronic kidney disease (CKD) ≥3 (aOR: 1.16, 95 % CI: 1.11-1.22, P < 0.01), end-stage renal disease (ESRD) (aOR: 1.75, 95 % CI: 1.61-1.90, P < 0.01), and anemia (aOR: 1.23, 95 % CI: 1.18-1.28, P < 0.01) were associated with increased odds of readmission. CONCLUSION: Concomitant MS in patients undergoing TAVI is associated with higher readmission rates and total hospital costs. This can contribute significantly to healthcare-related burdens. Further studies are required to evaluate in-hospital outcomes and predictors of readmission in patients undergoing TAVI with the presence of concomitant MS.

Prevalence of face mask related complications among healthcare workers during the COVID-19 pandemic in Saudi Arabia.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, most healthcare workers (HCWs) were required to wear face masks for long periods of time. Since then, it has been shown that face masks have the potential to cause several physical adverse effects. This study aimed to estimate the prevalence of face mask-related complications among HCWs during the COVID-19 pandemic in Saudi Arabia. Furthermore, we compared the relationship between face mask usage with other variables, including the type of mask used and gender. METHODOLOGY: A cross-sectional study was conducted using convenience sampling, with a targeted sample of 517 participants (35% nonresponse). Data was collected via an electronic survey, the link for which was distributed through social media sites, such as WhatsApp and Twitter, to reach HCWs across Saudi Arabia. Data was analyzed using the SPSS software. RESULTS: Overall, 438 HCWs who wore N95 or surgical masks for 4 hours or more per day on average were recruited. Skin-related complications in the nasal area had the highest prevalence (342, 78.1%), followed by behind the ear area (333, 76.0%), cheeks (307, 70.1%), and chin (248, 56.6%). Other complications included headaches (226, 51.6%), and eye-related complications (211, 48.2%). All face mask-related complications, except for behind the ear skin complications, were more associated with female gender. CONCLUSIONS: Mask usage was significantly associated with the development of headaches, and eye, and skin-related complications. Female HCWs were more predisposed to these complications. Preventative measures and awareness activities should be considered to help reduce mask use related complications.

Frequency of Cardiac Valvulopathies in Patients With Marfan Syndrome: A Systematic Review and Meta-Analysis.

Marfan syndrome (MFS) is a progressive connective tissue disease with a broad range of clinical manifestations. We sought to establish the spectrum of structural valvular abnormalities as cardiovascular involvement has been identified as the most life-threatening aspect of the syndrome. This was a systematic review with a meta-analysis of studies indexed in Medline from the inception of the database to November 7, 2022. Using the random-effects model, separate Forest and Galbraith plots were generated for each valvular abnormality assessed. Heterogeneity was assessed using the I2 statistics whilst funnel plots and Egger's test were used to assess for publication bias. From a total of 35 studies, a random-effects meta-analysis approximated the pooled summary estimates for the prevalence of cardiac valve abnormalities as mitral valve prolapse 65% (95% CI: 57%-73%); mitral valve regurgitation 40% (95% CI: 29%-51%); aortic valve regurgitation 40% (95% CI: 28%-53%); tricuspid valve prolapse 35% (95% CI: 15%-55%); and tricuspid valve regurgitation 43% (95% CI: 8%-78%). Only one study reported on the involvement of the pulmonary valve (pulmonary valve prolapse was estimated at 5.3% (95% CI: 1.9%-11.1%) in a cohort of 114 patients with MFS). We believe this study provides a description of the structural valvular disease spectrum and may help inform providers and patients in understanding the clinical history of MFS in the current treatment era with its increased life expectancy.

Evaluation of patient health outcomes of a student-run free clinic in East Harlem.

BACKGROUND: Most United States medical schools have affiliated student-run free clinics, but the quality of services provided in such contexts compared to national metrics is unknown. This study determines whether a student-run, attending-supervised free clinic servicing a low-income and minority race patient population in New York City can meet national metrics of care. METHODS: Through chart review from January 1, 2020 to December 31, 2020, patient outcomes and service utilization in the Healthcare Effectiveness Data and Information Set were examined and compared to national rates of patients using Medicaid HMO or Medicare. Patients are ≥ 21 years of age, residents of East Harlem, and ineligible for health insurance because of legal residency requirements. The majority identify as Hispanic and speak Spanish as their primary language. All patients who were seen in the clinic during the 2020 calendar year were included. The primary study outcome is the number of Healthcare Effectiveness Data and Information Set measures in which patients, seen in a student-run free clinic, meet or exceed national comparisons. RESULTS: The healthcare outcomes of 238 patients, mean age 47.8 years and 54.6% female, were examined in 18 Healthcare Effectiveness Data and Information Set measures. The student-run free clinic met or exceeded national metrics in 16 out of 18 categories. CONCLUSIONS: The student-run free clinic met or exceeded the national standard of care according to national metrics. Evidence-based priorities have been clarified for future improvement. Other student-run free clinics should similarly evaluate the quality of their services.

Non-calcified plaque in asymptomatic patients with zero coronary artery calcium score: A systematic review and meta-analysis.

BACKGROUND: There is growing interest in understanding the coronary atherosclerotic burden in asymptomatic patients with zero coronary artery calcium score (CACS). In this population, we aimed to investigate the prevalence and severity of non-calcified coronary plaques (NCP) as detected by coronary CT angiography (CCTA), and to analyze the associated clinical predictors. METHODS: This was a systematic review with meta-analysis of studies indexed in PubMed/Medline and Web of Science from inception of the database to March 31st, 2023. Using the random-effects model, separate Forest and Galbraith plots were generated for each effect size assessed. Heterogeneity was assessed using the I2 statistics whilst Funnel plots and Egger's test were used to assess for publication bias. RESULTS: From a total of 14 studies comprising 37808 patients, we approximated the pooled summary estimates for the overall prevalence of NCP to be 10% (95%CI: 6%-13%). Similarly, the pooled prevalence of obstructive NCP was estimated at 1.1% (95%CI: 0.7%-1.5%) from a total of 10 studies involving 21531 patients. Hypertension [OR: 1.46 (95%CI:1.31-1.62)] and diabetes mellitus [OR: 1.69 (95%CI: 1.41-1.97)] were significantly associated with developing any NCP, with male gender being the strongest predictor [OR: 3.22 (95%CI: 2.17-4.27)]. CONCLUSION: There is a low burden of NCP among asymptomatic subjects with zero CACS. In a subset of this population who have clinical predictors of NCP, the addition of CCTA has a potential to provide a better insight about occult coronary atherosclerosis, however, a risk-benefit approach must be factored in prior to CCTA use given the low prevalence of NCP.

Suicide Risk Among US Veterans With Military Service During the Vietnam War.

Importance: There are persistent questions about suicide deaths among US veterans who served in the Vietnam War. It has been believed that Vietnam War veterans may be at an increased risk for suicide. Objective: To determine whether military service in the Vietnam War was associated with an increased risk of suicide, and to enumerate the number of suicides and analyze patterns in suicides among Vietnam War theater veterans compared with the US population. Design, Setting, and Participants: This cohort study compiled a roster of all Vietnam War-era veterans and Vietnam War theater veterans who served between February 28, 1961, and May 7, 1975. The 2 cohorts included theater veterans, defined as those who were deployed to the Vietnam War, and nontheater veterans, defined as those who served during the Vietnam War era but were not deployed to the Vietnam War. Mortality in these 2 cohorts was monitored from 1979 (beginning of follow-up) through 2019 (end of follow-up). Data analysis was performed between January 2022 and July 2023. Main Outcomes and Measures: The outcome of interest was death by suicide occurring between January 1, 1979, and December 31, 2019. Suicide mortality was ascertained from the National Death Index. Hazard ratios (HRs) that reflected adjusted associations between suicide risk and theater status were estimated with Cox proportional hazards regression models. Standardized mortality rates (SMRs) were calculated to compare the number of suicides among theater and nontheater veterans with the expected number of suicides among the US population. Results: This study identified 2 465 343 theater veterans (2 450 025 males [99.4%]; mean [SD] age at year of entry, 33.8 [6.7] years) and 7 122 976 nontheater veterans (6 874 606 males [96.5%]; mean [SD] age at year of entry, 33.3 [8.2] years). There were 22 736 suicides (24.1%) among theater veterans and 71 761 (75.9%) among nontheater veterans. After adjustments for covariates, Vietnam War deployment was not associated with an increased risk of suicide (HR, 0.94; 95% CI, 0.93-0.96). There was no increased risk of suicide among either theater (SMR, 0.97; 95% CI, 0.96-0.99) or nontheater (SMR, 0.97; 95% CI, 0.97-0.98) veterans compared with the US population. Conclusions and Relevance: This cohort study found no association between Vietnam War-era military service and increased risk of suicide between 1979 and 2019. Nonetheless, the 94 497 suicides among all Vietnam War-era veterans during this period are noteworthy and merit the ongoing attention of health policymakers and mental health professionals.

Effect of the COVID-19 Pandemic on the Epidemiology of Pediatric Traumatic Brain Injury in Brazil.

Aim In response to the coronavirus 2019 disease (COVID-19) pandemic, governments worldwide implemented measures to prevent infection, resulting in restricted school activities, restricted children's freedom of movement, and increased risk of violence and injuries at home, including traumatic brain injury (TBI), among children. In Brazil, the consequences of the COVID-19 pandemic on the causes, severity, and mortality of pediatric TBI have not yet been investigated. Thus, our study aimed to determine whether the COVID-19 pandemic has affected the epidemiology of pediatric TBI among Brazilian children. Materials and methods We investigated the patients with TBI aged <18 years who visited a tertiary trauma center in Brazil in 2019 and 2020. TBI-related variables, such as classification, mechanism, clinical manifestations, need for intervention, morbidity, and mortality, were recorded. Furthermore, we used a nationwide databank to collect information on mortality from external causes of trauma and violence in the pediatric population in 2019 and 2020. The Mann-Whitney test was used to compare quantitative variables related to the mechanisms and severity of TBI in both periods in order to determine the impact of the COVID-19 pandemic. Results Of the patients with traumatic brain injury, 1371 visited the trauma center in 2019 and 1052 in 2020. No difference was noted in the incidence rate of abusive head trauma between these periods (p=0.142) or in mortality from violence in Brazil. Recreational causes of pediatric TBI increased during the first year of the COVID-19 pandemic in Brazil and falls from bicycles significantly increased during the pandemic (p<0.001). Conclusion A global reduction in pediatric admissions to emergency rooms as well as no impact on mortality and severity of pediatric TBI were observed during the COVID-19 pandemic in Brazil. Additionally, a public education program regarding child safety during recreational activities, particularly how to avoid falls from bicycles was recommended.

Prunetin in a GPR30-dependent manner mitigates renal ischemia/reperfusion injury in rats via interrupting indoxyl sulfate/TLR4/TRIF, RIPK1/RIPK3/MLKL, and RIPK3/PGAM5/DRP-1 crosstalk.

The potential health benefits of phytochemicals in preventing and treating diseases have gained increasing attention. Here, we proved that the methylated isoflavone prunetin possesses a reno-therapeutic effect against renal ischemia/reperfusion (I/R) insult by activating G protein-coupled receptor 30 (GPR30). After choosing the therapeutic dose of prunetin against renal I/R injury in the pilot study, male Sprague Dawley rats were allocated into 5 groups; viz., sham-operated (SO), SO injected with 1 mg/kg prunetin intraperitoneally for three successive days, untreated I/R, I/R treated with prunetin, and I/R treated with G-15, the selective GPR30 blocker, followed by prunetin. Treatment with prunetin reversed the I/R renal injury effect and majorly restored normal renal function and architecture. Mechanistically, prunetin restored the I/R-induced depletion of renal GPR30, an impact that was canceled by the pre-administration of G-15. Additionally, post-administration of prunetin normalized the boosted inflammatory markers indoxyl sulfate, TLR4, and TRIF and abrogated renal cell demise by suppressing necroptotic signaling, verified by the inactivation of p-RIPK1, p-RIPK3, and p-MLKL while normalizing the inhibited caspase-8. Besides, prunetin reversed the I/R-mediated mitochondrial fission by inhibiting the protein expression of PGMA5 and p-DRP-1. All these favorable impacts of prunetin were nullified by G-15. To sum up, prunetin exhibited a significant reno-therapeutic effect evidenced by the enhancement of renal morphology and function, the suppression of the inflammatory cascade indoxyl sulfate/TLR4/TRIF, which turns off the activated/phosphorylated necroptotic trajectory RIPK1/RIPK3/MLKL, while enhancing caspase-8. Additionally, prunetin opposed the mitochondrial fission pathway RIPK3/PGMA5/DRP-1, effects that are mediated via the activation of GPR30.

Prevalence of adolescent-reported food insecurity and the determinants including coping strategies living in urban slum communities of Bangladesh during the era of COVID-19: a cross-sectional study.

BACKGROUND: As food insecurity (FI) continues to rise worldwide especially in developing countries like Bangladesh, adolescent experience of FI have received minimal attention globally. This study aimed to identify the prevalence of adolescent-reported FI and its association with individual and socio-environmental factors as well as coping strategies amongst a sample of adolescents living in urban slum areas of Bangladesh in the times of the Coronavirus 19 (COVID-19) pandemic. METHODS: A descriptive cross sectional study was conducted amongst 326 adolescents (12-18 years) living in the urban slums of Narayanganj, Dhaka from April to May, 2022. Adolescent-reported FI was assessed using a structured questionnaire adopted from Household Food Insecurity Access Scale (HFIAS). Descriptive statistics, Chi-square tests and ordinal logistic regression were used to draw inference. RESULTS: Prevalence of adolescent-reported FI was high (46.6% moderate and 29.8% severe). The likelihood of experiencing moderate or severe FI versus no/mild FI were 1.7 times (95% Confidence Interval (CI) [1.1, 2.5]) higher in younger adolescents and 5 times (95% CI [2.3, 12.7]) higher in unemployed youth. Socio-environmental factors determining the economic status of a household such as higher number of family members, only one earning family member, unemployed father, no household assets, food aid received by the family during pandemic and positive COVID-19 infection in family were associated with moderate and severe FI. Coping strategies such as a higher number of food seeking strategies (Adjusted Odds Ratio (AOR) 3.4, 95% CI [1.9, 5.9]), substance use (AOR 6.2, 95% CI [1.2, 31.7]) and stopping school (AOR 3.3, 95% CI [1.9, 5.7]) increased odds for moderate and severe FI. Stratified by drop-out of school status, an association between food seeking strategies and FI remained significant among those school-going, while there was no association among those dropping out of school. CONCLUSION: This study showed that adolescents living in urban slum communities in Bangladesh are at very high risk of FI and resort to harmful coping strategies. Our study highlights the importance of further research in adolescent reported FI and coping strategies in low to middle income countries (LMICs) and create appropriate interventions to lower FI among this group and improve their state of health and wellbeing.

Pre-Operative Ocular Findings and Long-Term Follow-Up in a Large Cohort of Non-Syndromic Unicoronal Craniosynostosis.

(1) Background: Non-syndromic unicoronal craniosynostosis (UCS) is associated with a high prevalence of ocular anomalies. Currently, the etiology of this association remains obscure, however, it is presumed to be primarily attributed to their orbital malformations and/or secondary to craniofacial surgery. We assessed pre-operative ophthalmological examinations of non-syndromic UCS patients and compared them with their postoperative outcomes and long-term follow-up. (2) Methods: A retrospective case series was conducted on medical records of patients with non-syndromic UCS at Sophia Children's Hospital, Rotterdam. Ophthalmologic examinations were collected at different time periods: T1 (first visit), T2 (<1 year after cranioplasty), and T3 (long-term follow-up at last visit). The McNemar's test was used for statistical analysis. (3) Results: A total of 101 patients were included, for whom examinations were available at T1 and T3. Patients had a mean age of 2.8 years (±2.7) and 9.5 (±4.9) at T1 and T3, respectively. At T1, 52 patients (51.5%) were diagnosed with strabismus, and 61 patients (60.4%) at T3. Vertical strabismus increased significantly from 23 patients (22.8%) at T1 to 36 patients (35.6%) at T3 (p = 0.011). Followed by astigmatism, which increased significantly from 38 (37.6%) at T1 to 59 (58.4%) patients at T3 (p = 0.001). T1 was available in 20 patients prior to fronto-orbital advancement (FOA), therefore, a sub-analysis was conducted on these patients, which was followed shortly after FOA at T2. Prior to FOA, strabismus was present in 11 patients (55.0%) and in 12 patients (60.0%) at T2. After FOA, strabismus worsened in two patients. (4) Conclusions: This study showed the high prevalence of ocular anomalies in patients with non-syndromic UCS before and after cranioplasty and at long-term follow-up. The findings of this study show that ophthalmic and orthoptic examinations are an important part of the optimal treatment of patients with non-syndromic UCS.

Non-Calcified Coronary Artery Plaque on Coronary Computed Tomography Angiogram: Prevalence and Significance.

OBJECTIVE: We aimed to assess the prevalence of non-calcified plaque (NCP) on computed tomography angiography (CCTA) in symptomatic and asymptomatic individuals. In addition, we seek to compare plaque assessment on CCTA with intravascular ultrasound-virtual histology (IVUS-VH) and to assess the prognostic value of non-calcified plaques (NCPs). BACKGROUND: The CCTA can characterize coronary plaques and help quantify burden. Furthermore, it can provide additional prognostic information which can enable further risk stratification of patients. METHODS: We performed a broad comprehensive review of the current literature pertaining to CCTA and primarily isolated NCP in symptomatic and asymptomatic patients. In addition, our review included studies correlating plaque on CT with IVUS-VH. CONCLUSIONS: NCP is the initial precursor of calcified plaque and serves as a prominent marker of early coronary atherosclerosis. By detecting NCP during early stages, several measures can be implemented which can alter the evolutionary course of the underlying disease. This can potentially lead to a lower incidence of cardiovascular events.

Comparative Analysis of Reinforced Asphalt Concrete Overlays: Effects of Thickness and Temperature.

Reflection cracking in asphalt concrete (AC) overlays is a common form of pavement deterioration that occurs when underlying cracks and joints in the pavement structure propagate through an overlay due to thermal and traffic-induced movement, ultimately degrading the pavement's lifespan and performance. This study aims to determine how alterations in overlay thickness and temperature conditions, the incorporation of chopped fibers, and the use of geotextiles influence the overlay's capacity to postpone the occurrence of reflection cracking. To achieve the above objective, a total of 36 prism specimens were prepared and tested using an overlay testing machine (OTM). The variables considered in this study were the thickness of the overlay (40, 50, and 60 mm), temperature (20, 30, and 40 °C), mix type (reference mix and mix modified with 10% chopped fibers by weight of asphalt cement), and the inclusion of geotextile fabric at two positions (one-third of the depth from the base and at the bottom). The research outcomes revealed that a decreased temperature and thicker overlay led to a higher resistance to crack initiation and full propagation, as indicated by the values of critical fracture energy (Gc) and crack progression rate (CPR). Furthermore, the study observed the enhanced crack resistance of overlays in the presence of geotextiles, whether at the bottom or one-third of the depth from the bottom, with superior performance of the former. Despite a slight enhancement in certain properties, the incorporation of chopped fibers in the overlays did not substantially improve the overall performance compared to the reference specimens. Overall, the study provides valuable insights into the variables that influence the ability of AC overlays to mitigate reflection cracking. These findings will aid engineers and designers in making informed decisions regarding overlay design and construction.

Torticollis in Non-Syndromic Unicoronal Craniosynostosis Is Predominantly Ocular Related.

(1) Background: Patients with unicoronal craniosynostosis (UCS) often show torticollis which can result from either an ocular cause or contraction of the sternocleidomastoid muscle. For clinicians, it is crucial to know the prevalence of ocular torticollis (OT) to ensure appropriate referral for treatment. Furthermore, associated ophthalmic features with OT in these patients are scarcely described. The aim of this study was to determine the prevalence of OT in non-syndromic UCS patients and investigate its associated ophthalmic features. (2) Methods: In this descriptive cross-sectional study medical records of non-syndromic UCS patients treated between 1994-2022 in one tertiary care hospital in The Netherlands were retrospectively reviewed. Collected data included: diagnosis and type of torticollis, binocular single vision (BSV), strabismus, ocular motility, alphabetical patterns, refractive error, and amblyopia. Patients were classified as OT, based on their ophthalmic and/or orthoptic diagnosis. Prevalence was determined with the 95% CI using the Clopper-Pearson exact test. Associations between OT and the ophthalmic features were determined using Chi-square or Fishers' exact test and its effect size was calculated using Cramer's V. (3) Results: In total, 146 patients were included, of whom 57 had torticollis. An ocular cause for the torticollis was found in 54 patients. The prevalence of OT was 37% (n = 146; 95% CI [0.292-0.454]). Significant associations were found between OT and strabismus (p < 0.001), ocular motility abnormalities (p < 0.001), alphabetical patterns (p < 0.001), and amblyopia (p = 0.002). BSV (p = 0.277) and refractive error (p = 1.0) were not significantly associated with OT. However, in OT the BSV was relatively poor (42.1%) and more frequently absent (26.3%) compared to the non-torticollis group (7% poor and 16.3% absent). In both groups, excyclotorsion was predominantly present (62.3%). (4) Conclusions: In 95% of cases, torticollis in UCS patients is ocular-related. Overall, one in three patients with UCS have OT. This study emphasizes the importance of a timely referral of all patients with UCS with torticollis to an orthoptist and/or ophthalmologist, specialized in diagnosing and treatment of OT, before considering physiotherapy.

A systematic review and meta-analysis of the prevalence, incidence, and predictors of atrial fibrillation in cardiac sarcoidosis.

BACKGROUND: The occurrence of atrial arrhythmias, in particular, atrial fibrillation (AF) in patients with cardiac sarcoidosis (CS) are of growing interest in the field of infiltrative cardiomyopathies. Via a systematic review with meta-analysis, we sought to synthesize data on the prevalence, incidence, and predictors of atrial arrhythmias as well as outcomes in patients with CS. METHODS: PubMed/Medline, Web of Science, and Scopus were systematically queried from inception until April 26th, 2023. Using the random-effects model, separate plots were generated for each effect size assessed. RESULTS: From a total of 8 studies comprising 978 patients with CS, the pooled summary estimates for the prevalence of AF was 23% (95% CI: 13%-34%). Paroxysmal AF was the most common subtype of AF (83%; 95% CI: 77%-90%), followed by persistent AF (17%; 95% CI: 10%-23%). In 9 studies involving 545 patients with CS, the pooled incidence of AF was estimated at 5%, 13.1%, and 8.9% at <2 years, 2-4 years, and > 4 years of follow-up respectively, with an overall cumulative incidence of 10.6% (95% CI: 4.9%-17.8%) over a 6-year follow-up period. Increased left atrial size and atrial 18F-fluorodeoxyglucose uptake were identified as strong independent predictors for the development of atrial arrhythmias on qualitative synthesis. CONCLUSION: The burden of AF and related arrhythmias in CS patients is considerable. This necessitates close follow-up and predictive risk-stratification tools to guide the initiation of appropriate strategies, including therapeutic interventions for prevention of AF-related embolic phenomenon, especially in those with known clinical predictors.

Predictors of non-calcified plaque presence and future adverse cardiovascular events in symptomatic rural Appalachian patients with a zero coronary artery calcium score.

BACKGROUND: Coronary artery calcium (CAC) scoring is a proven predictor for future adverse cardiovascular events (CVE) in asymptomatic individuals. Data is emerging regarding the usefulness of non-calcified plaque (NCP) assessment on cardiac computed tomography (CCT) angiography in symptomatic patients with a zero CAC score for further risk assessment. METHODS: A retrospective review from January 2019 to January 2022 of 696 symptomatic patients with no known CAD and a zero CAC score identified 181 patients with NCP and 515 patients without NCP by a visual assessment on CCT angiography. The primary endpoint was to identify predictors for NCP presence and adverse CVEs (death, myocardial infarction, or cerebrovascular accident) within two years. RESULTS: Based on logistic regression, age (OR 1.039, 95% CI [1.020-1.058], p â€‹< â€‹0.001), diabetes mellitus (OR 2.192, 95% CI [1.307-3.676], p â€‹< â€‹0.003), tobacco use (OR 1.748, 95% CI [1.157-2.643], p â€‹< â€‹0.008), low-density lipoprotein cholesterol level (OR 1.009, 95% CI [1.003-1.015], p â€‹< â€‹0.002), and hypertension (OR 1.613, 95% CI [1.024-2.540], p â€‹< â€‹0.039) were found to be predictors of NCP presence. NCP patients had a higher pretest probability for CAD using the Morise risk score (p â€‹< â€‹0.001∗), with NCP detection increasing as pretest probability increased from low to high (OR 55.79, 95% CI [24.26-128.26], p â€‹< â€‹0.001∗). 457 patients (66%) reached a full two-year period after CCT angiography completion, with NCP patients noted to have shorter follow-up times and higher rates of elective coronary angiography, intervention, and CVEs. The presence of NCP (aOR 2.178, 95% CI [1.025-4.627], p â€‹< â€‹0.043) was identified as an independent predictor for future adverse CVEs when adjusted for diabetes mellitus, age, and hypertension. CONCLUSION: NCP was identified at high rates (26%) in our symptomatic Appalachian population with no known CAD and a zero CAC score. NCP was identified as an independent predictor of future adverse CVEs within two years.