Post Hoc Research Articles

Joint attention and maternal attention across varying dyadic interactions for autistic children

BackgroundJoint attention (JA) is an area of delay associated with autism. Individual differences in JA are shown to relate to language development. The present study examined JA initiations (IJA) and responses to JA (RJA) of autistic children in structured and unstructured contexts with their mothers to examine the relation between mother attention and JA. MethodForty-two autistic children (ages 2.5 to 5.5 years) and their mothers engaged in 15 m interactions in three social contexts (competing demands, teaching, free play). Children were categorized by language level into limited language (N = 20) and verbal (N = 21) groups based on ADOS-2 module to assess group and contextual differences. Contingency analyses assessed bi-directional temporal relations between observed child JA and mother attention in lagged intervals. ResultsRate of children’s IJA and maternal attention differed depending on the context of their interaction. Child IJA and mother attention showed a bi-directional temporally contingent association such that child IJA predicted subsequent maternal attention, and maternal attention predicted subsequent child IJA. RJA was unrelated to maternal attention in contingency analyses. Post-hoc analyses indicated a language level group by receptive communication, and group by expressive communication interaction on the contingency between child IJA and subsequent mother attention such that a stronger contingency emerged for dyads wherein children had limited language. ConclusionsThe present study illustrates the important role that children’s social communication behaviors may have within mother-child social interactions, and how children’s verbal ability, as well as the context of the social interaction may influence bi-directional social attention.

Trueness of the apical and middle root portion segments of 3D-printed removable die and alveolar cast designs manufactured using stereolithographic 3D printing.

The present study evaluated the effects of the root portion design, segment (middle vs. apical), and part (die vs. cast) on the trueness of three-dimensional (3D)-printed removable die-cast complex. The trueness of apical and middle segments of the root portion of 45 3D-printed removable dies and casts with three different root portion designs (n = 15) was assessed using a metrology-grade computer program. The three removable dies and cast designs (root form [RF], conical [CON], and cylindric [CYL]) were created using professional computer-aided manufacturing computer programs (DentalCAD 3.1 Rijeka, and InLab CAD 22.0), and manufactured using stereolithographic 3D printer (Form3; FormLabs, Somerville, MA). Subsequently, the 3D-printed removable dies and casts were scanned by a single operator with an intraoral scanner (PrimeScan; Dentsply Sirona, Charlotte, NC), and their respective standard tessellation language files were aligned and compared to master reference files in a metrology-grade computer program (Geomagic Control X; 3D systems, Rock Hill, NC). The root mean square (RMS) values of the middle and apical segments for each removable die and cast were calculated and analyzed using a mixed model including a repeated measure 3-way analysis of variance (ANOVA) and post-hoc stepdown Bonferroni-corrected pairwise comparisons (α = 0.05). A statistically significant 3-way interaction between factors was detected, suggesting that the part (removable die or alveolar cast) and their design affected the RMS values of their apical and middle root portion segment. (p = 0.045). The post-hoc analysis identified significant differences between RMS values of the apical segments of the CON and CYL removable dies (p = 0.005). Significant differences were observed between the middle and apical segments of the CON (p < 0.001) and RF removable die designs (p = 0.004). No statistically significant differences were noticed between the RMS of the different alveolar cast designs (p > 0.05). Significant differences were detected between the apical and middle segments of the same alveolar cast design (p < 0.05). For the manufacturing trinomial and 3D printing strategy used in the present study, the interaction of the part, design, and segment affected the trueness of removable dies and alveolar casts. The trueness was higher on the middle segment on removable dies and alveolar casts in all designs used, except for CYL removable dies, where the trueness difference between segments was small. Higher trueness values may be achieved with designs with simple apical segment geometries.

The effect of irrigation solution temperature and novel heat-treated rotary files on apical debris extrusion and canal preparation time.

This study aimed to compare apical debris extrusion and canal preparation time with ProTaper Gold (PTG) and ProTaper Ultimate (PTU) files at different temperatures. Mesio-buccal roots of 60 mandibular first molars were distributed into six groups depending on the file type (PTG, PTU) and irrigation solution temperature (20, 37, 45°C). During instrumentation, extruded debris were collected and weighed to measure the mass in milligrams. The canal preparation time was recorded in seconds. ANOVA followed by Bonferroni post-hoc tests were used for analysis. The amount of debris extrusion was significantly higher in PTU, which was affected by the irrigation solution temperature (p < 0.05). The difference in canal preparation time was not significant between the two file systems, however, it was significant between the different temperatures (p = 0.001). Both file systems had shorter canal preparation times at 20°C. The irrigation solution temperature could influence the debris extrusion and time of canal preparation.

Body composition as a determinant of the therapeutic index with androgen signaling inhibition.

Androgen signaling is central to prostate cancer and men's health. Prior data indicates that increasing body fat is unfavorable in the localized setting yet associated with favorable outcomes in men with metastatic disease. Understanding the biological links between adiposity and prostate cancer may optimize the therapeutic index with ASI. We hypothesized that host adiposity and androgen synthesis are linked to the efficacy and toxicity of ASI for men with metastatic castration-resistant prostate cancer (mCRPC). A post-hoc analysis was done of NCT02703623 where men with mCRPC (n = 186) were treated for 8 weeks with abiraterone acetate, prednisone, and apalutamide (AAPA), and a satisfactory response was defined as a PSA decline >50%. Body composition was measured on baseline CT scans. Germline DNA WES was performed with a focus on variants in steroidogenic genes. Adipokine levels were measured in pre-treatment plasma. Germline polymorphisms in 3 genes involved in androgen synthesis (AKR1C3 rs12529, CYP17A1 rs6162, SRD5A2 rs523349) were associated with differences in body composition at baseline on ADT alone (prior to receipt of AAPA). Elevated subcutaneous adipose tissue index (SATi, p = 0.02), visceral adipose tissue index (VATi, p = 0.03), and BMI (p = 0.04) were associated with satisfactory response to AAPA. Leptin had positive correlation with VATi (r = 0.47) and SATi (r = 0.48). Inherited polymorphisms in androgen synthesis correlated with differences in body composition after exposure to ADT and warrant further investigation as candidate markers for body composition toxicity. Elevated subcutaneous and visceral adiposity were associated with improved response to ASI.

Longitudinal Evaluation of Reproductive Endocrine Function in Men with ACTH-Dependent Cushing Syndrome.

Hypogonadism may be caused by Cushing syndrome (CS) and may intensify its adverse consequences. To determine the frequency of male hypogonadism before and after curative surgery for CS, and its cause. Post-hoc analyses of prospective cohort studies. Clinical research center. Men with ACTH-dependent CS. Cohort 1 (C1) (n=8, age 32.5±12 y; studied 1985-1989); Cohort 2 (C2) (n=44, 42.7 ± 15.1 y; studied 1989-2021). C1: Every 20-minute blood sampling for 24h before and 1-40 months after surgical cure. Three subjects underwent GnRH stimulation tests pre- and post-surgery. C2: Hormone measurements at baseline and 6 and 12 months (M) post-cure. C1: LH, FSH, LH pulse frequency and LH response to GnRH. C2: LH, FSH, testosterone (T), free T, fT4, T3, TSH and UFC levels and frequency of hypogonadism pre- and post-surgery. C1: mean LH and LH pulse frequency increased after surgery (p < 0.05) without changes in LH pulse amplitude, mean FSH, or peak gonadotropin response to GnRH. C2: 82% had baseline hypogonadism (total T 205 ± 28 ng/dL). Thyroid hormone levels varied inversely with UFC and cortisol. LH, total and free T, and SHBG increased at 6M and 12M post surgery, but hypogonadism persisted in 51% at 6M and in 26% at 12M. Hypogonadism in men with CS is widely prevalent but reversible in ∼75% of patients one year after surgical cure and appears to be mediated through suppression of hypothalamic GnRH secretion, and modulated by thyroid hormones.

Extended thromboprophylaxis in heart failure patients; the unmet need.

Heart failure (HF) is considered one of a leading cause of cardiovascular morbidity and mortality worldwide. The association between HF and venous thromboembolism (VTE) has been reported in several studies owing to many physiological and thromboembolic risk factors. Thus, the need for extended thromboprophylaxis during the post-discharge period in HF patients has been evaluated. Most guidelines do not recommend extended thromboprophylaxis because of its uncertain benefits and increased risk of bleeding. However, recent evidence in HF patients revealed no increased risk of bleeding with extended thromboprophylaxis, which highlights the importance of identifying ideal candidates who might benefit from extended thromboprophylaxis. Several risk assessment models (RAMs) have been developed to identify patients at a high risk of VTE who would benefit from in-hospital and post-discharge prophylactic anticoagulation therapy based on the risk-benefit principle. However, their accuracy in predicting VTE is questionable, and none have a standardized approach for evaluating the risk of VTE in HF patients. In this review, we provided an overview of the incidence and pathophysiology of VTE in HF patients, a summary of guideline recommendations for VTE prevention, and a summary of studies evaluating the use of extended thromboprophylaxis, with a focus on subgroup or post-hoc analyses of HF patients. We also discussed the need to design an ideal RAM that can identify candidate patients for extended thromboprophylaxis by stratifying the risk of VTE and identifying the key risk factors for bleeding in medically ill patients, including those with HF.

Sleep Problems and Gambling Disorder: Cross-Sectional Relationships in a Young Cohort.

To investigate the potential association between gambling disorder and symptoms of sleep problems (including insomnia and excessive daytime sleepiness). It was hypothesised that, compared to controls, individuals with gambling disorder would have significantly greater disturbance of sleep, as indicated by increased scores in: (1) sleep items on the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Rating Scale for Depression (HAM-D); (2) total score on the HAM-A and HAM-D; and (3) the Epworth Sleepiness Scale (ESS). Secondary analysis of previously published data from 152 young adults, aged 18-29 years. Individuals were stratified into three groups: controls, those at risk of gambling disorder, and those with gambling disorder. One-way ANOVAs with post-hoc tests were conducted to determine whether groups differed significantly in sleep item scores and total scores of the HAM-A and HAM-D, and the ESS. HAM-D scale insomnia item scores were significantly higher in the disorder group, when compared to controls, this being particularly marked for middle and late insomnia. The HAM-A item score indicated significantly worse sleep quality in the disorder group, compared to at risk and control groups. Total HAM-A and HAM-D scores were significantly higher in the disorder group, but ESS scores did not differ significantly. Measures of disruptions in sleep were significantly higher in gambling disorder than controls. Anxiety and depressive symptom severity was also significantly higher in the gambling disorder group. Further research could have implications for identification and treatment of sleep disorders and psychiatric comorbidities in gambling disorder.

Acute physiological effects on macromolecule digestion following oral ingestion of the enzyme blend Elevase® in individuals that had undergone an ileostomy, but were otherwise healthy—a randomized, double blinded, placebo-controlled exploratory study

Digestive enzymes can selectively degrade proteins, carbohydrates and lipids; and their supplementation alongside food may accelerate the breakdown of complex food matrices, facilitate greater nutrient absorption, decrease food sensitivities and aid in the management of certain disease states. Several intrinsic and extrinsic factors govern food digestion and for every individual this phenomenon is unique. This study was conducted as a randomized, crossover, placebo-controlled design where each participant served as their own control. This post-hoc analysis investigated the impact of a dietary enzyme supplementation blend known as Elevase® on dietary macromolecule digestion in samples from otherwise healthy participants that had previously undergone a small bowel resection, resulting in an ileostomy (NCT04489810). This is the first time this study-paradigm has been used for the assessment of in vivo dietary breakdown following enzyme supplementation. Arguably, this technique offers superior data when compared to that generated in artificial gut digestion models, preclinical animal models, or indeed conventional clinical studies using stool analyses, as it allows real-time access to samples in situ in the small intestine where the majority of nutritional absorption takes place. It was demonstrated that after 4 h, Elevase® significantly increased monosaccharide levels (predominantly glucose and fructose) in the ileostomy samples taken from the same individuals on the same diet on a different day. In addition, the bile salt taurohyodeoxycholic acid was also increased, suggesting a physiological host response to the macromolecule digestion induced by the enzymatic blend. Overall, these findings suggest Elevase® could accelerate food digestion and potentially increase nutrient availability from the diet.

Successful evaluation of a new image-based parameter for the diagnosis of carpal tunnel syndrome: ultrasound assessment of longitudinal median nerve gliding in patients, healthy volunteers, and cadavers.

Reduced longitudinal median nerve gliding is a new promising diagnostic feature in carpal tunnel syndrome (CTS). However, the complexity of existing ultrasound analysis protocols undermines the application in routine clinical practice. To provide a simple method for assessing longitudinal gliding with ultrasound, without the need for post-hoc image analysis. 1) Retrospective cohort study, validation by external blinded reviewers; 2) proof of concept in body donors. 1) Outpatient clinic; 2) anatomy department. The population included 48 patients with idiopathic CTS diagnosed by electrodiagnostic testing and ultrasound, as well as 15 healthy controls. Twelve, non-frozen, non-embalmed body donors were enrolled. Longitudinal gliding of the median nerve in the carpal tunnel was visualized in all patients with idiopathic CTS and healthy controls. All ultrasound videos were pseudonymized, equipped with a scale, and randomized. Videos were analyzed by four independent radiologists, all blinded to clinical characteristics. The endpoint was gliding rated as millimeters. Validity of the technique was tested by using speckle tracking software, and in body donors, directly measuring nerve excursion in situ, simultaneously to ultrasound. Gliding differed significantly between controls and patients with CTS, decreasing with incremental CTS severity. A cut-off value of 3.5 mm to identify patients with CTS, yielded 93.8% sensitivity and 93.3% specificity. Intraclass correlation coefficient among senior author and raters was 0.798 (95% CI 0.513 to 0.900, P<0.001), indicating good reliability. Speckle tracking and especially direct validation in body donors correlated well with ultrasound findings. First, longitudinal median nerve gliding can reliably be assessed using this simple technique without the need for complicated procedures. Second, a decrease in gliding was found with progressive severity of CTS. Reproducibility for measured distances is good among raters. An easy to apply sonography parameter would bolster the diagnostic ability of specialists in physical medicine and rehabilitation in daily routine.

Comparison of Gout Flares With the Initiation of Treat-to-Target Allopurinol and Febuxostat: A Post-Hoc Analysis of a Randomized Multicenter Trial.

Initiating urate-lowering therapy (ULT) in gout can precipitate arthritis flares. There have been limited comparisons of flare risk during the initiation and escalation of allopurinol and febuxostat, administered as a treat-to-target strategy with optimal anti-inflammatory prophylaxis. This was a post-hoc analysis of a 72-week randomized, double-blind, placebo-controlled, noninferiority trial comparing the efficacy of allopurinol and febuxostat. For this analysis, the occurrence of flares was examined during weeks 0 to 24 when ULT was initiated and titrated to a serum urate (sUA) goal of less than 6 mg/dl (<5 mg/dl if tophi). Flares were assessed at regular intervals through structured participant interviews. Predictors of flare, including treatment assignment, were examined using multivariable Cox proportional hazards regression. Study participants (n = 940) were predominantly male (98.4%) and had a mean age of 62.1 years with approximately equal proportions receiving allopurinol or febuxostat. Mean baseline sUA was 8.5 mg/dl and all participants received anti-inflammatory prophylaxis (90% colchicine). In a multivariable model, there were no significant associations of ULT treatment (hazard ratio [HR] 1.17; febuxostat vs allopurinol), ULT-dose escalation (HR 1.18 vs no escalation), prophylaxis type, or individual comorbidity with flare and no evidence of ULT-dose escalation interaction. Factors independently associated with flare risk during ULT initiation/escalation included younger age, higher baseline sUA, and absence of tophi. These results demonstrate that gout flare risk during the initiation and titration of allopurinol is similar to febuxostat when these agents are administered according to a treat-to-target strategy using gradual ULT-dose titration and best practice gout flare prophylaxis.

Lipidomic-Based Algorithms Can Enhance Prediction of Obstructive Coronary Artery Disease.

Lipidomics emerges as a promising research field with the potential to help in personalized risk stratification and improve our understanding on the functional role of individual lipid species in the metabolic perturbations occurring in coronary artery disease (CAD). This study aimed to utilize a machine learning approach to provide a lipid panel able to identify patients with obstructive CAD. In this posthoc analysis of the prospective CorLipid trial, we investigated the lipid profiles of 146 patients with suspected CAD, divided into two categories based on the existence of obstructive CAD. In total, 517 lipid species were identified, from which 288 lipid species were finally quantified, including glycerophospholipids, glycerolipids, and sphingolipids. Univariate and multivariate statistical analyses have shown significant discrimination between the serum lipidomes of patients with obstructive CAD. Finally, the XGBoost algorithm identified a panel of 17 serum biomarkers (5 sphingolipids, 7 glycerophospholipids, a triacylglycerol, galectin-3, glucose, LDL, and LDH) as totally sensitive (100% sensitivity, 62.1% specificity, 100% negative predictive value) for the prediction of obstructive CAD. Our findings shed light on dysregulated lipid metabolism's role in CAD, validating existing evidence and suggesting promise for novel therapies and improved risk stratification.

Evaluating psychological distress associated with life events under the traumatic experience threshold in patients with major depressive and bipolar disorder

Patients with bipolar disorder (BD) and major depressive disorder (MDD) experience psychological distress associated with daily events that do not meet the threshold for traumatic experiences, referred to as event-related psychological distress (ERPD). Recently, we developed an assessment tool for ERPD, the ERPD-24. This tool considers four factors of ERPD: feelings of revenge, rumination, self-denial, and mental paralysis. We conducted a cross-sectional study between March 2021 and October 2022 to identify the differences and clinical features of ERPD among patients with MDD and BD and healthy subjects who did not experience traumatic events. Specifically, we assessed ERPD using the ERPD-24 and anxiety-related symptoms with the State-Trait Anxiety Inventory, Liebowitz Social Anxiety Scale, and anxious-depressive attack. Regarding the ERPD-24 scores among the groups, as the data did not rigorously follow the test of normality, the Kruskal–Wallis test was used to compare the differences among the groups, followed by the Dunn–Bonferroni adjusted post-hoc test. Non-remitted MDD patients and BD patients, regardless of remission/non-remission, presented more severe ERPD than healthy subjects. This study also demonstrated the relationships between all anxiety-related symptoms, including social phobia and anxious-depressive attack and ERPD, in both BD and MDD patients and in healthy subjects. In conclusion, patients with non-remitted MDD and with BD regardless of remission/non-remission experience severe ERPD related to anxiety-related symptoms.

Detecting depression severity using weighted random forest and oxidative stress biomarkers

This study employs machine learning to detect the severity of major depressive disorder (MDD) through binary and multiclass classifications. We compared models that used only biomarkers of oxidative stress with those that incorporate sociodemographic and health-related factors. Data collected from 830 participants, based on the Patient Health Questionnaire (PHQ-9) score, inform our analysis. In binary classification, the Random Forest (RF) classifier achieved the highest Area Under the Curve (AUC) of 0.84 when all features were included. In multiclass classification, the AUC improved from 0.84 with only oxidative stress biomarkers to 0.88 when all characteristics were included. To address data imbalance, weighted classifiers, and Synthetic Minority Over-sampling Technique (SMOTE) approaches were applied. Weighted random forest (WRF) improved multiclass classification, achieving an AUC of 0.91. Statistical tests, including the Friedman test and the Conover post-hoc test, confirmed significant differences between model performances, with WRF using all features outperforming others. Feature importance analysis shows that oxidative stress biomarkers, particularly GSH, are top ranked among all features. Clinicians can leverage the results of this study to improve their decision-making processes by incorporating oxidative stress biomarkers in addition to the standard criteria for depression diagnosis.

Synthetic and Natural Vitamin C Modulation of Leaded Paint-Induced Nephrotoxicity of Automobile Painters in Ile-Ife, Nigeria.

Introduction: Lead (Pb) occupational exposure in painters has been documented to be contacted via additives in paints due to its many important properties and vitamin C has been the most widely studied when it comes to Pb- induced oxidative stress.  Aim: This study aimed at the use of freshly squeezed orange-juice due to its accessibility in investigating the modulating role of synthetic and natural vitamin-C on leaded paint-induced nephrotoxicity of automobile painters.  Study Design and Methods: Sixty (60) male automobile painters were consecutively selected and divided equally into 2 groups. Vitamin-C and orange juice were administered daily to painters for 4 weeks at dosage levels of 200 and 184 mg/day respectively. Thirty (30) male non-painters constituted the control group. Orange juice vitamin-C content was assessed by titrimetric method and synthetic vitamin-C served as the standard drug. Renal biomarkers and reduced glutathione (GSH) were done by Colorimetry. Urine aminolevulinic acid (ALA) and Pb were assessed by ELISA technique and atomic absorption spectrophotometry respectively. Phytochemical screenings (quantitative/qualitative) and proximate analysis were done using standard methods. Data were analyzed using Pearson’s correlation coefficient and One-way Analysis of Variance (ANOVA) followed by Tukey’s post-hoc test for pairwise comparison. Statistical significance was p&lt; 0.05.  Results: Baseline results at 0-week of orange juice administered group showed a significantly (P&lt;0.05) higher serum Pb, urea and creatinine compared to non- painters. Also, their urine baseline results at 0-week showed a significantly (P&lt;0.05) higher levels of ALA and GSH compared to non-painters. Orange juice administration at 4 weeks showed significant (P&lt;0.05) reductions in concentrations of lead, urea, and creatinine in serum, decreased concentrations of GSH and ALA in urine but increased urine Pb compared to baseline. However, compared with baseline, after 4 weeks of vitamin-C supplementation, serum Pb, urine GSH, and urine ALA were significantly (P&lt;0.05) reduced and urine Pb significantly (P&lt;0.05) increased. A positive correlation was observed at 2-weeks of taking orange- juice between serum lead and urine ALA (r= 0.703) and GSH (r= 0.913) but 4-week positive correlation between urea and urine GSH (r= 1.000). A negative correlation was observed at 2-week of taking vitamin-C between serum creatinine and urine lead (r= -0.857) while 4-week a negative correlation was observed between urine GSH and urine lead (r= -0.743). Presence of tannin, phenol, saponin, alkaloid, and flavonoid was detected in orange juice.  Conclusion: Orange juice administration conferred significant amelioration to renal and lead toxicity biomarkers by 4 weeks. The presence of phytochemicals suggests why orange juice may be a viable alternative in amelioration of toxic effects of leaded paint among automobile painters.

A novel risk classification model integrating CEA, ctDNA, and pTN stage for stage 3 colon cancer: a post hocanalysis of the IDEA-France trial.

We assessed the added value of incorporating carcinoembryonic antigen (CEA) to circulating tumor DNA (ctDNA) and pathological TN (pTN) stage for risk classification in stage 3 colon cancer (CC). We retrospectively analyzed postoperative CEA values in patientswith CC from the IDEA-France phase 3 trial. The relation between disease-free survival (DFS) and CEA was modeled through restricted cubic splines. Prognostic value of CEA, ctDNA, and pTN was assessed with the Kaplan-Meier method. Multivariate analysis was used to identify prognostic and predictive factors for DFS. Among 696 patients (35%), CEA values were retrievable, and for 405 (20%) both CEA and ctDNA were available. An optimized CEA threshold of 2ng/mL was identified, the 3-year DFS was 66.4% for patients above the threshold and 80.9% for those below (HR, 1.74; 95% CI, 1.33-2.28, P < .001). In multivariate analysis, CEA ≥ 2ng/mL contributed significantly to model variability, becoming an independent prognostic factor for DFS (HR, 1.82; 95% CI,1.27-2.59), alongside ctDNA (HR, 1.88; 95% CI, 1.16-3.03) and pTN (HR, 1.78; 95% CI, 1.24-2.54). A novel integrated risk classification combining CEA, ctDNA, and pTN stage reclassified 19.8% of pT4/N2 patients as low risk and 2.5% of pT3/N1 patients as high risk. This new classification demonstrated the 3-year DFS of 80.8% for low-risk patients and 55.4% for high-risk patients (HR, 2.66, 95% CI, 1.84-3.86, P < .001). Postoperative CEA value is a prognostic factor for DFS in stage 3 CC, independently of ctDNA and pTN. It advocates for systematic reporting in future adjuvant trials. Integrating both biomarkers with pTN could refine risk classification in stage 3 CC.

Prognostic significance of neutrophil to lymphocyte ratio (NLR) in oral squamous cell carcinoma

BackgroundTumor microenvironment is one of the evading research in the progression of cancers. Circulating neutrophils reflect the system's inflammatory response and study the growth of tumor cells thereby inducing cancer progression. Aim and objectivesThe current study aims to evaluate the NLR ratio in oral squamous cell carcinoma group and to compare it with that of normal control and Premalignant group. Material and methodsThis study is retrospective, the medical records of 48 OSCC patients, 48 Leukoplakia patients, and 48 normal healthy controls were taken. Association between NLR and clinicopathological variables were assessed. Tukey's post-hoc test was done to compare the variables. Kaplan Meier analysis was done for the analysis of overall survival. ResultsThe NLR ratio was assessed and compared between the three groups. The mean NLR ratio was found to be 3.79 in Oral squamous cell carcinoma patients, 2.62 in leukoplakia patients, and 2.07 in the normal control group. ConclusionAn increase in NLR levels was seen in OSCC patients. Increased NLR was also seen associated with advanced tumor staging and grading.

The Extent of Implementation and Influence of Boys and Girls Brigade Philippines (BGBP) Programs

This study examines the extent of implementation and influence of the Boys and Girls Brigade Philippines (BGBP) programs. Its objectives are twofold: first, to assess the extent of implementation of its programs and determine their impact on its recipients; and second, to introduce a quality program for other institutions to adopt in addressing current societal challenges and preparing students for the VUCA world. The research employs a descriptive comparative design, utilizing both quantitative and qualitative data analysis methods. The quantitative data analysis used mean scores, frequency count, Kruskal-Wallis H Test, and Post-Hoc Analysis (Dwass-Steel-Critchlow-Fligner Pairwise Comparison). Qualitative data were analyzed using thematic analysis. The study involved 144 respondents, including administrators, teachers, students, and alumni of BGBP. Key findings reveal that all the BGBP programs are highly implemented. Also, all the BGBP programs are highly influential. There is a highly significant difference in the perception of administrators, teachers, and students on the implementation and influence of the programs. The program offers numerous benefits, such as spiritual growth, learning to live and lead for Christ, and developing leadership skills. Challenges faced include leadership issues, financial constraints, inconsistency in implementation, students’ attitudes, and parental support. To enhance the program, recommendations include strengthening the set standard, elevating the mentoring system, reinforcing parental involvement, and seeking financial support. Additionally, policymakers and curriculum makers may consider adopting BGBP as a benchmark, as it addresses current challenges and prepares students for the rapidly changing world.

Prevalence of preexisting articular bone pathology in patients with osteoarthritis screened for fasinumab clinical trials identified by X-ray or magnetic resonance imaging

ObjectiveTo examine the prevalence of preexisting articular bone pathology in patients with hip or knee pain due to osteoarthritis (OA) screened for fasinumab clinical trials. MethodThis post-hoc analysis included patients with OA screened for three phase 3 fasinumab studies (NCT02683239, NCT03161093, NCT03304379). During screening, participants who met other clinical inclusion/exclusion criteria underwent radiography of knees, hips, and shoulders. Those with Kellgren–Lawrence grade (KLG) ≥2 for index joint and without an exclusionary finding proceeded to magnetic resonance imaging (MRI) of index, contralateral, and KLG ≥3 joints. Exclusionary findings included bone fragmentation/collapse, bone loss/resorption, osteonecrosis, and fracture, by either X-ray or MRI. Participants with extensive subchondral cysts were also excluded. Prevalence of abnormalities on radiographs and MRIs are reported. ResultsOf 27,633 participants screened, 21,997 proceeded to imaging. Of these, 1203 (5.5%) were excluded due to the presence of ≥1 joint with severe articular bone pathology (X-ray or MRI): bone fragmentation/collapse (2.61%), subchondral insufficiency fracture (SIF; 1.67%), osteonecrosis (1.11%), and significant bone loss (0.32%). Additionally, 3.14% screen-failed due to extensive subchondral cysts. More than half of the exclusions due to bone fragmentation/collapse (386/572), osteonecrosis (141/245) and significant bone loss (59/71), and approximately one third of SIF (133/367) and extensive subchondral cysts (229/689) were evident on X-rays. ConclusionsApproximately one in 20 participants with OA who met the clinical screening criteria for fasinumab phase 3 trials were later excluded due to preexisting severe articular bone pathology findings by X-ray or MRI.

Effects of Zibotentan Alone and in Combination with Dapagliflozin on Fluid Retention in Patients with CKD.

Endothelin receptor antagonists (ERAs) reduce albuminuria but are limited by fluid retention risk, particularly in patients with chronic kidney disease (CKD). Combining ERAs with sodium-glucose cotransporter 2 (SGLT2) inhibitors, which have diuretic effects, offers a promising strategy to mitigate fluid retention. In this post-hoc analysis of the ZENITH-CKD trial, we assessed fluid dynamics in patients with CKD treated with the ERA zibotentan alone, and in combination with the SGLT2 inhibitor dapagliflozin. In ZENITH-CKD, 508 patients with CKD (estimated glomerular filtration rate ≥ 20 mL/min/1.73m2 and a urinary albumin-to-creatinine ratio of 150-5000 mg/g) were randomized to treatment with placebo, dapagliflozin 10 mg plus placebo, zibotentan (0.25, 1.5 or 5 mg) plus dapagliflozin 10 mg and zibotentan 5 mg plus placebo. We evaluated correlations between changes in fluid retention markers and bioimpedance-measured extracellular fluid (ECF) in response to zibotentan treatment. We used Cox proportional hazards regression to assess the association between zibotentan/dapagliflozin treatment, baseline characteristics, and fluid retention, and the relationship between zibotentan plasma exposure and fluid retention. After 3 weeks of treatment with zibotentan 0.25, 1.5 or 5 mg plus dapagliflozin 10 mg, changes in body weight (β=0.36 [95%CI 0.26,0.45]) per kg, B-type natriuretic peptide (β=0.38 [95%CI 0.22, 0.54]) per doubling, and hemoglobin (β=-0.29 [95%CI -0.48, -0.10]) per g/dL were independently associated with changes in ECF. Higher doses of zibotentan were associated with significantly higher risk of fluid retention compared to dapagliflozin alone (zibotentan 5 mg HR 8.50 (95%CI 3.40, 21.30). The hazard ratio attenuated when zibotentan was combined with dapagliflozin (HR zibotentan/dapagliflozin 5/10 mg 3.09 [95%CI 1.08, 8.80], zibotentan/dapagliflozin 1.5/10 mg 2.70 [95%CI 1.44, 5.07] and zibotentan/dapagliflozin 0.25/10 mg HR 1.21 [95%CI 0.50, 2.91]). The risk of fluid retention was higher with higher zibotentan exposure and lower eGFR. High doses of zibotentan were associated with a higher risk of fluid retention, which was attenuated with lower doses and the addition of dapagliflozin.

Cerebral blood flow in relation to peripheral endothelial function in youth bipolar disorder

IntroductionAnomalous cerebral blood flow (CBF) is evident in bipolar disorder (BD), however the extent to which CBF reflects peripheral vascular function in BD is unknown. This study investigated endothelial function, an index of early atherosclerosis and cardiovascular disease risk, in relation to CBF among youth with BD. MethodsParticipants included 113 youth, 13–20 years old (66 BD; 47 healthy controls [HC]). CBF was measured using arterial spin labeling with 3 T MRI. Region of interest analyses (ROI; global grey matter, middle frontal gyrus, anterior cingulate cortex, temporal cortex, caudate) were undertaken alongside voxel-wise analyses. Reactive hyperemia index (RHI), a measure of endothelial function, was assessed non-invasively via pulse amplitude tonometry. General linear models were used to examine RHI and RHI-by-diagnosis associations with CBF, controlling for age, sex, and body mass index. Bonferroni correction for multiple comparisons was used for ROI analyses, such that the significance level was divided by the number of ROIs (α = 0.05/5 = 0.01). Cluster-extent thresholding was used to correct for multiple comparisons for voxel-wise analyses. ResultsROI findings were not significant after correction. Voxel-wise analyses found that higher RHI was associated with lower left thalamus CBF in the whole group (p < 0.001). Additionally, significant RHI-by-diagnosis associations with CBF were found in three clusters: left intracalcarine cortex (p < 0.001), left thalamus (p < 0.001), and right frontal pole (p = 0.006). Post-hoc analyses showed that in each cluster, higher RHI was associated with lower CBF in BD, but higher CBF in HC. ConclusionWe found that RHI was differentially associated with CBF in youth with BD versus HC. The unanticipated association of higher RHI with lower CBF in BD could potentially reflect a compensatory mechanism. Future research, including prospective studies and experimental designs are warranted to build on the current findings.