Age-matched Controls Research Articles

Role of Serum Magnesium on Insulin Resistance in Overweight and Obese Children.

Background Childhood obesity has become a global epidemic, with projections indicating it could affect 25% of children under 16 by 2050. This rise poses significant health risks, including early onset of type 2 diabetes and cardiovascular diseases. Recent research has shown a correlation between insulin action and magnesium levels, highlighting the link between low serum magnesium levels and obesity. This study aimed to investigate the relationship between serum magnesium levels and obesity in children aged 5-16 years, to compare overweight and obese adolescents with age- and gender-matched controls, and to determine the association between insulin resistance and decreased serum magnesium levels. Methodology At a tertiary hospital, this 1.5-year cross-sectional comparativestudy investigated the relationship between magnesium levels in the blood and insulin resistance in children aged 5-16. Cases met the 2015 revised Indian Academy of Pediatrics (IAP) growth charts for overweight or obesity in comparison to age-matched healthy controls. Exclusions included secondary causes of obesity and medical complications affecting magnesium. Assessments involved clinical history, examination, and fasting blood tests for insulin resistance indices. Results Compared to the controls, overweight children showed that mean serum magnesium levels are lower (1.03 mEq/l vs. 1.85 mEq/l, p<0.001); they were also reflected in higher anthropometric measures, which include body mass index (BMI) and body fat percentage. Cases had significantly higher metabolic markers like fasting insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index, and lipid profiles, whereas systolic blood pressure although showing recognized differences did not significantly differ. Conclusion The study underscored the importance of detecting magnesium levels on insulin resistance in overweight and obese children.

Does Parkinson's disease affect verb production in picture descriptions?

Research on Parkinson's disease (PD) has documented significant deficits in verb production, with more robust results in single word retrieval tasks than in connected speech, yet the underlying causes of these deficits are disputable, especially concerning connected speech production. We analyzed picture descriptions provided by 48 individuals with PD and 48 age-matched healthy controls, and examined the percent of nouns and verbs of all words, the number of described events, verbs denoting activity, verbs in active morpho-syntactic patterns, and transitive verbs. Individuals with PD produced a lower percent of verbs than did control participants, but the groups differed in no other variable. Scores on a cognitive screening task associated with the percent of verbs and the number of events. We suggest that verb retrieval in connected speech in PD reflects no specific difficulty with action semantics, but rather the spread of PD pathology into more diffuse verb-specific neural networks.

Adynamic spoken language in corpus callosum dysgenesis

Corpus callosum dysgenesis (CCD) is a congenital brain malformation that occurs when the development of the corpus callosum is disrupted, either partially or completely. The cognitive outcomes in individuals with CCD vary greatly, but generally the neuropsychological profile is characterised by slow processing speed, poor transfer of interhemispheric sensory-motor information, and impaired complex problem solving. Core language skills are often preserved in CCD, but there is some evidence that complex language may be impaired. Thus, the current study sought to examine whether spontaneous speech output was reduced in a cohort of individuals with CCD compared to age-matched controls. We further explored a series of factors that may be contributing to poor spontaneous speech in CCD, such as difficulties generating, selecting, and sequencing ideas for expression, as well as apathy and slowed processing speed. A cohort of 25 individuals with CCD and 39 neurotypical controls were enrolled in this study. Participants completed a picture description task to measure spontaneous speech output, alongside a series of cognitive and language baseline tests. Verbal and nonverbal fluency tasks gauged idea generation and sequencing, and sentence-level selection tasks measured idea selection. We found that, despite having largely intact core language skills, individuals with CCD produced significantly less spontaneous speech on the picture description task than controls. This language profile may be described as “adynamic”. Further, we found that poor spontaneous speech output in CCD was related to problems generating ideas for expression, as individuals with CCD performed below controls on the verbal and nonverbal fluency tasks. Exploratory analyses revealed that apathy and slowed processing speed may be contributing factors. Adynamia in CCD is a novel finding that may be an intervention target for improving communication skills in this population.

Abstract B053: SUMOylation and TIGIT inhibition: a novel immunotherapy combination for pancreatic cancer

Abstract Introduction: Immune checkpoint inhibitors have shown promise in many other solid tumors but have been disappointing in pancreatic ductal adenocarcinoma (PDAC). Preclinical work demonstrates that the immune checkpoint receptor TIGIT plays a key role in PDAC immune evasion and may be a better therapeutic target than the PD1 or CTLA4 axes. Post-translational small-ubiquitin-like modification (SUMOylation) regulates the activity of numerous proteins involved in cell proliferation. Our laboratory has shown that inhibition of SUMOylation with small molecule TAK-981 favorably modulates the PDAC immune microenvironment and specifically increases the expression of TIGIT binding partners CD226 on immune cells and CD155 on tumor cells. We hypothesized that inhibition of SUMOylation with small molecule TAK-981 would synergize with anti-TIGIT antibody therapy to induce anti-tumor immunity. Methods:All studies utilized a murine PDAC organoid line (KPC46) derived from a liver metastasis in a genetically engineered mouse model (KPC). KPC46 consistently metastasizes to the liver when implanted orthotopically into the tail of the pancreas in immunocompetent mice. Following tumor implantation, mice were surveilled by ultrasound until tumors reached 5-7 mm in diameter, then randomized to one of two treatment groups: TAK-981 + anti-TIGIT or vehicle control (n=10/group). Monotherapies were not included, as each drug alone did not produce significant responses in prior studies using this model. The treatment cohort received 15 mg/kg of TAK-981 and 100 micrograms of anti-TIGIT antibody via intraperitoneal injection every 48 hours starting 14 and 15 days, respectively, post-implantation, for a total of 4 weeks. Complete responders were defined as absence of disease after 2 months of observation. Complete responders and age-matched controls (n=3/group) were rechallenged with subcutaneous tumor injection and monitored for tumor development. Results:Survival of PDAC mice was significantly prolonged in the combination group when compared to the control group (median survival 81 vs 42 days, P&amp;lt;0.05). A total of 4 mice (40%) were deemed complete responders after 2 months of monitoring. The re-challenge experiment produced tumors in all three control mice but none of the treated mice by 4 weeks after implantation. Conclusion:In this study, we explored the combination of two promising immunotherapy agents for PDAC which demonstrated significant additive effects generating durable and complete responses. We were able to confirm the presence of protective immunity. These results are rarely seen in PDAC experiments. Further experiments to better understand and optimize these effects are underway. These drugs are currently in clinical trials for solid tumors and could feasibly be studied in the near future in PDAC. Citation Format: Jorge R de la Torre Medina, Utsav Joshi, Jaynath Shankara Narayanan, Herve Tiriac, Yuan Chen, Rebekah White. SUMOylation and TIGIT inhibition: a novel immunotherapy combination for pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B053.

Tenascin C Deletion Impairs Tendon Healing and Functional Recovery After Rotator Cuff Repair.

The biological factors that affect healing after rotator cuff repair (RCR) are not well understood. Genetic variants in the extracellular matrix protein Tenascin C (TNC) are associated with impaired tendon healing and it is expressed in rotator cuff tendon tissue after injury, suggesting it may have a role in the repair process. The purpose of the current study was to determine the role of TNC on tendon healing after RCR in a murine model. The supraspinatus tendon was transected and repaired on the left shoulder of Wild-Type (WT-RCR), Tenascin C null (Tnc --RCR) and Tnc heterozygous (Tnc +/--RCR) mice. Controls included the unoperated, contralateral shoulder of WT-RCR, Tnc - RCR, Tnc +/--RCR mice and unoperated shoulders from age and genotype matched controls. We performed histologic, activity testing, RNA-seq, and biomechanical analyses. At 8-weeks post-RCR, Tnc - and Tnc +/- mice had severe bone and tendon defects following rotator cuff repair. Tnc --RCR mice had reduced activity after rotator cuff repair including reduced wheel rotations, wheel duration, and wheel episode average velocity compared with WT-RCR. Loss of Tnc following RCR altered gene expression in the shoulder, including upregulation of sex hormone and WNT pathways and a downregulation of inflammation and cell cycle pathways. Tnc - mice had similar biomechanical properties after repair as WT. Further research is required to evaluate tissue specific alterations of Tnc, the interactions of Tnc and sex hormone and inflammation pathways as well as possible adjuvants to improve enthesis healing in the setting of reduced TNC function.

Evaluation of Serum Ferritin, Iron and C-Reactive Protein Level in Children with Febrile Seizure in Wasit Province, Iraq

Background: Febrile seizures are a commonplace pediatric neurological sickness, often related to fever and infections. Recent research suggest a capability hyperlink among iron deficiency, inflammation, and the prevalence of febrile seizures, but the relationship remains underexplored in particular populations. This study aimed to assess the affiliation between serum iron, ferritin levels, and inflammatory markers (C-reactive protein [CRP] and white blood cell [WBC] remember) in youngsters with febrile seizures in comparison to healthful controls.Methods: A case-manage study become performed involving a hundred youngsters aged 6 months to 6 years, with 50 kids who skilled febrile seizures (patient institution) and 40 age-matched healthful controls. Serum ferritin, iron, CRP degrees, and WBC counts had been measured and compared between the 2 groups. The data have been analyzed the usage of impartial t-assessments, Pearson correlation, and multivariate logistic regression.Results: Children within the febrile seizure institution had extensively decrease serum ferritin (40.5 ± 30.2 ng/mL) and iron levels (40.8 ± 15.3 μg/dL) as compared to controls (85.7 ± 20.4 ng/mL and 75.4 ± 18.7 μg/dL, respectively; p &lt; 0.001). CRP ranges and WBC counts had been notably better within the affected person organization (25.6 ± 48 mg/L and 18,400 ± 5,200 cells/μL, respectively) compared to controls (2.3 ± 1.1 mg/L and 7,200 ± 1,800 cells/μL; p &lt; 0.001). A robust bad correlation was observed among CRP ranges with each serum ferritin (r = -0.462) and serum iron (r = -0.625). Multivariate logistic regression identified lower serum iron and ferritin stages, and better CRP and WBC counts as good sized unbiased predictors of febrile seizures.Conclusion: The findings advise that iron deficiency and accelerated inflammatory markers are tremendous chance factors for febrile seizures in kids. These effects highlight the importance of monitoring iron repute and managing inflammation in pediatric sufferers prone to febrile seizures.

Correlation analysis of airway space and condylar morphology in bilateral idiopathic condylar resorption patients.

To evaluate the airway space in bilateral idiopathic condylar resorption (ICR) patients and analyse the correlation between the morphological characteristics of the condyles and airway parameters. In all, 35 female patients with bilateral ICR (mean age: 21.6 years) and 35 age-matched female controls (mean age: 21.3 years) were included. Airway parameters were measured using CBCT. Independent T-tests were used to analyse the differences between the bilateral ICR group and the control group, and then the correlation between airway parameters and condylar parameters was detected using Pearson correlation analysis. p < .05 was considered statistically significant. Patients with bilateral ICR showed a significant decrease in airway volume, minimum axial area and sagittal sectional area (p < .05). The bilateral condylar axial angle positively correlated with airway volume and sagittal sectional area (p < .05). In contrast, the bilateral condylar neck angle negatively correlated with sagittal sectional area (p < .05). None of the condylar parameters showed a correlation with minimum axial area of the airway in the bilateral ICR group (p > .05). Bilateral ICR significantly affects patients' airway space. The condylar axial angle and neck angle correlate with airway parameters.

Abstract C061: Loss of CaMK2B accelerates tumor formation and enhances metastatic competency in genetically engineered mouse models of PDAC

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer- related deaths in the United States and is often not diagnosed until it has already metastasized. Our prior work established that calcium signaling pathways facilitate a pro-metastatic phenotype through the induction of an epithelial-to-mesenchymal transition (EMT) program in PDAC tumor cells, but the downstream signaling molecules mediating this phenotype have remained elusive. MethodsUsing a novel genetically engineered model of pancreatic cancer, we demonstrate that loss of Calcium/calmodulin-dependent kinase-II B (CaMK2B), a downstream effector kinase activated by calcium, enhances cellular plasticity, and increases metastasis. To this end, we generated a genetically engineered mouse model where Camk2b was knocked out in tumor cells in a lineage-labeled Kras- and p53-driven PDAC mouse model (herein KPCY-Camk2bcKO). Results Genetic deletion of Camk2b in the KPCY genetically engineered model accelerated tumor formation and dramatically reduced the overall median survival of KPCY- Camk2b cKO mice (78 days) relative to KPCY controls (136 days). Pathological and immunofluorescence analysis of KPCY-Camk2b cKO animals showed an increased number of poorly differentiated tumor regions and a higher metastatic burden, with &amp;gt;85% of KPCY- Camk2b cKO animals presenting with multi-focal metastases. Further analysis of tumor cells in KPCY-Camk2b cKO mice showed enhanced expression of markers of the highly aggressive squamous PDAC subtypes. Strikingly, Camk2b deletion combined with oncogenic Kras G12D (in the absence of p53 alterations), was sufficient to form lethal metastatic PDAC tumors, while age-matched control Kras G12D tumors with intact Camk2b only progressed to the acinar-to-ductal metaplasia (ADM) or Pancreatic Intraepithelial Neoplasia (PanIN) stage. Collectively, these results establish Camk2b loss as a new oncogenic and pro-metastatic mechanism in PDAC Conclusion This work demonstrates that Camk2b loss enhances tumor cell evolution and plasticity within PDAC to promote metastasis. In this context, we speculate that loss of Camk2b rewires calcium signaling to drive an aggressive subtype of PDAC with increased metastasis. Citation Format: Jessica Peura, Nikita Bhalerao, Calvin Johnson, Yamini Ogoti, Faith Keller, Emma Watson, Zhen Zhao, Jason Pitarresi. Loss of CaMK2B accelerates tumor formation and enhances metastatic competency in genetically engineered mouse models of PDAC [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C061.

Choroidal thickness in type 2 diabetes mellitus patients using spectral domain optical coherence tomography

To measure the choroidal thickness in patients with type 2 diabetes mellitus and its comparison to healthy age-matched individuals.This prospective comparative study conducted at departments of Ophthalmology, Shri B.M. Patil Medical College, Hospital and Research Centre, Vijayapura. Study included 192 patients, 96 with diabetes and 96 age-matched controls. Data acquired comprised demographics, a thorough eye examination, fundus photography and spectral domain optical coherence tomography measurements of choroidal thickness using enhanced depth imaging.Mean age was 60.17±7.727 years with male predominance in both cases and controls. The mean duration of diabetes was 5.67±3.39 years. Positive correlation was noted between duration of diabetes and severity of retinopathy (p = 0.001). 21 patients did not have any evidence of diabetic retinopathy, while 75 patents had features of non-proliferative diabetic retinopathy, of which (31) had mild, (21) moderate, (12) severe and (11) with proliferative diabetic retinopathy. Mean choroidal thickness of controls was 327.308±18.945 microns, as compared to thinner choroids 295±15.082 microns in cases without retinopathy and 271 ± 36.122, 242 ±30.048, 193±15.748 microns in mild, moderate, severe non-proliferative diabetic retinopathy respectively and 191.492± 23.834 microns in proliferative diabetic retinopathy. Statistically significant differences were noted on comparing choroidal thickness between controls and cases (p = 0.001).Choroidal thickness was maximum in control group with a p value of &amp;#60;0.001, while cases showed overall thinner choroids with increasing severity of retinopathy. Thinnest choroids were observed in patient with proliferative diabetic retinopathy. Choroidal thickness can be used as a non-invasive prognostic bio marker for diabetic retinopathy.

PSI-21 Limited impact of hypothyroidism on porcine fetal growth during mid to late gestation

Abstract In the fetal pig, both circulating thyroid hormone and growth rate are known to increase throughout gestation; however, the functional association between these coincident factors has not been established. Thus, the objective of this project was to investigate this cause-and-effect relationship by evaluating the impact of induced fetal hypothyroidism on fetal growth during mid to late gestation. To induce fetal hypothyroidism, n = 12 pregnant gilts were orally treated with the goitrogen methimazole (MMI) at a dose of 5 mg/kg/d for 21 d, with n = 3 gilts starting treatment on gestation d 34, 45, 55 and 65. An equivalent group n = 12 of gilts were sham treated for the same periods to produce gestationally age-matched euthyroid control litters (CON). Upon completion of the treatment period, gilts were humanely euthanized, and the resulting populations of n = 174 MMI and n = 166 CON fetuses deeply phenotyped. No meconium-stained fetuses were observed at any time point, and only 5 mummified fetuses were observed (3 CON, 2 MMI), indicating treatment has no effect on fetal viability. Fetal body weight (BW) and the weights of individual organs including thyroid, liver, heart, lung, kidney, spleen, and brain were collected. In addition, fetuses were imaged in both left and right lateral recumbency for subsequent morphometric assessment using a custom analysis pipeline in ImageJ. Image analysis yielded parameters including crown-rump length, girth, brow length, depth at the snout/skull junction, depth at the snout/nose junction, and area under the skull curvature (AUC). Left and right measurements for all morphometric parameters were found to be highly correlated (r2 &amp;gt; 0.9) indicating a repeatable measure using this approach. Statistical analysis of all phenotypic differences was carried out using a linear mixed effect model including gestational age and treatment as fixed effects and gilt as a random effect. A significant increase in both absolute and relative thyroid weights indicated the development of goiter and thus, successful induction of hypothyroidism within the MMI litters. In addition, a significant treatment by time interaction was observed, with 0.014 g and 0.21 g increase at d 55 and 66, respectively, indicating reduced compensatory action within the fetal hypothalamic-pituitary-thyroid axis during this earliest period. Liver weight as a percentage of BW decreased from 6.06% to 2.56% between d 55 and 86 in the CON group but was significantly increased at all time points in response to MMI induced hypothyroidism (P &amp;lt; 0.01). A corresponding increase in brain to liver weight ratio over time was suppressed in MMI fetuses (P &amp;lt; 0.05). While all other phenotypic parameters were significantly altered by gestational age, there was no significant impact of fetal hypothyroidism. Collectively, the results indicate that fetal growth during mid to late gestation is not driven by fetal thyroid hormone.

Meta-analysis of bone mineral density in adults with phenylketonuria

BackgroundLifelong management of phenylketonuria (PKU) centers on medical nutrition therapy, including dietary phenylalanine (Phe) restriction in addition to Phe-free or low-Phe medical foods/protein substitutes. Studies have reported low bone mineral density (BMD) in mixed-age PKU populations, possibly related to long-term Phe restriction. Therefore, a meta-analysis investigating BMD specifically in adults with PKU was conducted.MethodsStudies reporting BMD-related outcomes were identified from a systematic literature review evaluating somatic comorbidities experienced by adults with PKU on a Phe-restricted diet (searched February 1, 2022, updated November 1, 2023). Risk of study bias was assessed (Scottish Intercollegiate Guidelines Network checklists). The primary outcome of the meta-analysis was pooled mean BMD Z-scores of different bones. Secondary outcomes were the prevalence of low BMD Z-scores at pre-specified thresholds. Subgroup analyses of mean BMD Z-scores (decade of study publication, controlled versus uncontrolled blood Phe levels, gender) were conducted.ResultsBMD-related data from 4097 individuals across 10 studies rated as at least acceptable quality were included. Mean BMD Z-scores were statistically significantly lower compared with an age-matched control or reference (non-PKU) population, across bones, but still within the expected range for age (> -2.0): lumbar spine (seven studies, n = 304), -0.63 (95% confidence interval (CI): -0.74, -0.52); femoral neck (four studies, n = 170), -0.74 (95% CI: -1.25, -0.22); radius (three studies, n = 114), -0.77 (95% CI: -1.21, -0.32); total body (four studies, n = 157), -0.61 (95% CI: -0.77, -0.45). The small number of observations in the subgroup analyses resulted in a high degree of uncertainty, limiting interpretation. Estimated prevalence of BMD Z-scores ≤ -2.0 was 8% (95% CI: 5%, 13%; four studies, n = 221) and < -1.0 was 42% (95% CI: 35%, 51%; five studies, n = 144).ConclusionsAdults with PKU had lower BMD Z-scores than the reference (non-PKU) population but < 1 in 10 were below the expected range for age. The low number of studies prevents identification of which population characteristics are most impacting BMD.This meta-analysis was supported by BioMarin Pharmaceutical Inc., Novato, CA and is registered with the Research Registry (reviewregistry1476).

Impaired arterial dilation and increased NOX2 generated oxidative stress in subjects with ataxia-telangiectasia mutated (ATM) kinase

BackgroundSubjects with mutations in the Ataxia-Telangiectasia mutated (ATM) gene encoding for ATM kinase have a greater predisposition to develop atherosclerosis, but the mechanism behind this phenomenon is not yet understood. NADPH oxidase type 2 may play a role in this process, leading to endothelial dysfunction and an increased susceptibility to thrombosis. The purpose of this study was to assess the redox state in individuals with ATM mutations and determine its impact on endothelial function. MethodsIn this cross-sectional study, twenty-seven children with ataxia telangiectasia (AT) (13 males and 14 females, mean age 15.1 ± 7.6 years) were compared with 27 controls (13 males and 14 females, mean age 14.6 ± 8.4 years) matched for age and gender. Additionally, 29 AT parents with heterozygous mutation of ATM (h-ATM) gene, and 29 age- and gender-matched controls were included. Endothelial function was evaluated through brachial flow-mediated dilation (FMD) and the assessment of nitric oxide (NO) bioavailability. Oxidative stress was evaluated by measuring serum activity of soluble NOX2-dp (sNOX2-dp), hydrogen peroxide (H2O2) production, and hydrogen breakdown activity (HBA). Thrombus formation was assessed through the Total Thrombus Formation Analysis System (T-TAS). ResultsAT children and parents with heterozygous ATM mutations exhibited significantly lower FMD, HBA, and NO bioavailability as compared to age and gender matched controls. AT children and ATM carrier of heterozygous ATM mutations had significantly higher concentrations of sNOX2-dp and H2O2 as compared to controls. Compared to the respective controls, AT children and their parents, who carried heterozygous ATM mutation, showed an accelerated thrombus growth as revealed by reduced occlusion time. Multivariable linear regression analysis revealed that sNOX2 (standardized coefficient β: −0.296; SE: 0.044; p = 0.002) and NO bioavailability (standardized coefficient β: 0.224; SE: 0.065; p = 0.02) emerged as the only independent predictive variables associated with FMD (R2: 0.44). ConclusionsThis study demonstrates that individuals with ATM mutations experience endothelial dysfunction, increased oxidative stress, and elevated thrombus formation. These factors collectively contribute to the heightened susceptibility of these individuals to develop atherosclerosis.

Brain glycogen build-up measured by magnetic resonance spectroscopy in classic infantile Pompe disease.

Classic infantile Pompe disease is caused by abnormal lysosomal glycogen accumulation in multiple tissues, including the brain due to a deficit in acid α-glucosidase. Although treatment with recombinant human acid α-glucosidase has dramatically improved survival, recombinant human acid α-glucosidase does not reach the brain, and surviving classic infantile Pompe patients develop progressive cognitive deficits and white matter lesions. We investigated the feasibility of measuring non-invasively glycogen build-up and other metabolic alterations in the brain of classic infantile Pompe patients. Four classic infantile patients (8-16 years old) and 4 age-matched healthy controls were scanned on a 7 T MRI scanner. We used T2-weighted MRI to assess the presence of white matter lesions as well as 1H magnetic resonance spectroscopy and magnetic resonance spectroscopy imaging to obtain the neurochemical profile and its spatial distribution, respectively. All patients had widespread white matter lesions on T2-weighted images. Magnetic resonance spectroscopy data from a single volume of interest positioned in the periventricular white matter showed a clear shift in the neurochemical profile, particularly a significant increase in glycogen (result of acid α-glucosidase deficiency) and decrease in N-acetyl-aspartate (marker of neuronal damage) in patients. Magnetic resonance spectroscopy imaging results were in line and showed a widespread accumulation of glycogen and a significant lower level of N-acetyl-aspartate in patients. Our results illustrate the unique potential of 1H magnetic resonance spectroscopy (imaging) to provide a non-invasive readout of the disease pathology in the brain. Further study will assess its potential to monitor disease progression and the correlation with cognitive decline.

Identifying neural correlates of balance impairment in traumatic brain injury using partial least squares correlation analysis

Objective.Balance impairment is one of the most debilitating consequences of traumatic brain injury (TBI). To study the neurophysiological underpinnings of balance impairment, the brain functional connectivity during perturbation tasks can provide new insights. To better characterize the association between the task-relevant functional connectivity and the degree of balance deficits in TBI, the analysis needs to be performed on the data stratified based on the balance impairment. However, such stratification is not straightforward, and it warrants a data-driven approach.Approach.We conducted a study to assess the balance control using a computerized posturography platform in 17 individuals with TBI and 15 age-matched healthy controls. We stratified the TBI participants into balance-impaired and non-impaired TBI usingk-means clustering of either center of pressure (COP) displacement during a balance perturbation task or Berg Balance Scale score as a functional outcome measure. We analyzed brain functional connectivity using the imaginary part of coherence across different cortical regions in various frequency bands. These connectivity features are then studied using the mean-centered partial least squares correlation analysis, which is a multivariate statistical framework with the advantage of handling more features than the number of samples, thus making it suitable for a small-sample study.Main results.Based on the nonparametric significance testing using permutation and bootstrap procedure, we noticed that the weakened theta-band connectivity strength in the following regions of interest significantly contributed to distinguishing balance impaired from non-impaired population, regardless of the type of stratification:left middle frontal gyrus, right paracentral lobule, precuneus, andbilateral middle occipital gyri. Significance.Identifying neural regions linked to balance impairment enhances our understanding of TBI-related balance dysfunction and could inform new treatment strategies. Future work will explore the impact of balance platform training on sensorimotor and visuomotor connectivity.

Short-latency afferent inhibition and its relationship to covert sensory and motor hand impairment in multiple sclerosis

ObjectiveTo investigate sensorimotor integration by quantifying short-latency afferent inhibition (SAI) in people with MS who experience manual dexterity problems compared to controls. Methods22 people with MS with self-reported manual dexterity problems and 10 sex and age-matched controls were assessed using various upper extremity clinical tests. SAI was assessed by a transcranial magnetic stimulation pulse over the primary motor cortex preceded by peripheral nerve stimulation to the median nerve at 6 interstimulus intervals 2 – 8 ms longer than individualized N20 latencies. ResultsAlthough within normal limits, persons with MS exhibited significantly slower Nine Hole Peg Test performance and pinch strength in the dominant hand. They also exhibited greater sensory impairment (monofilament test) in the dominant hand. Persons with MS showed significantly greater disinhibition of SAI in the dominant hand compared to controls, which was significantly correlated with weaker pinch strength. ConclusionReduced SAI in people with MS, particularly in the dominant hand, signifies disruptions in cortical cholinergic inhibitory activity and is associated with lower pinch strength. SignificanceEvaluating changes in SAI may offer insight into the disrupted cortical cholinergic inhibitory activity that contributes to sensorimotor disintegration, potentially advancing disease management in persons with MS.

Renal structural changes and apelin receptor expression in spontaneously hypertensive rats: implications for hypertension-induced kidney injury.

Arterial hypertension is a primary risk factor for kidney disease. Recent advances have implied a potential link between the apelin system and renal homeostasis. We used 6- and 12-month-old spontaneously hypertensive rats and age-matched normotensive controls to assess the changes in the renal expression of the apelin receptor by immunohistochemical method. The study also evaluated correlations between the renal apelin receptor's expression and renal injury indicators. The histological analysis showed elevated glomerular sclerosis and tubulointerstitial damage indices in both groups of hypertensive rats compared to age-matched controls. Older rats within each group exhibited higher scores than younger ones. The immunohistochemical analysis revealed varying apelin receptor expression patterns, with tubular expression intensifying both with hypertension severity and age. Glomerular expression was notably higher in older hypertensive rats compared to normotensive controls. We reported significant positive correlations between glomerular apelin receptor expression and glomerular sclerosis index in older hypertensive animals. Similarly, a positive correlation between tubular apelin receptor expression and tubulointerstitial damage index was discovered in hypertensive rats, suggesting hypertension-related changes in apelin receptor expression and renal damage. Our study found kidney changes and varying apelin receptor correlations in hypertensive rat kidneys, suggesting complex roles needing research.

Topological structural characteristics in patients with systemic lupus erythematosus with and without neuropsychiatric symptoms

PurposeThis study investigated the topological structural characteristics of systemic lupus erythematosus (SLE) with and without neuropsychiatric symptoms (NPSLE and non-NPSLE), and explore their clinical implications.MethodsWe prospectively recruited 50 patients with...

Drawing promotes memory retention in a patient with sleep-related anterograde amnesia.

Drawing is a powerful tool to enhance memory in healthy participants and patients with probable dementia. Here, we investigated whether the drawing effect could extend to patient CT, a young woman with severe anterograde amnesia. Following surgery for a midline tumor involving her septum pellucidium and extending down into her fornices bilaterally, CT experienced a severe case of sleep-related amnesia. She can remember information encountered throughout the day, but when waking up in the morning or following a nap she forgets information learned prior to sleep. Here, we tested CT and 21 age-matched controls in a 3-day within-subjects design, during which participants encoded words by either drawing or writing them down. Memory for encoded words was tested in two conditions that each followed a 12-h delay, once after a night of sleep, and once after 12 h of wake. Despite her severe memory impairment, CT showed a drawing effect that was comparable to controls in both sleep and wake conditions. Whereas CT's memory for written words was consistently impaired relative to controls, her memory for drawn words was at the lower control range following a waking delay and above chance following a sleep delay. We suggest that amnesic patients may benefit from the drawing effect due to the recruitment of brain regions outside of the hippocampal system for encoding and consolidation. Furthermore, in control participants, sleep benefited memory for written words, but not for drawn words, suggesting that sleep preferentially consolidates memories that are more dependent on the hippocampal system.

Tear film parameters and meibography in eyes of children with vernal keratoconjunctivitis.

To study tear film parameters and Meibomian glands in pediatric patients with vernal keratoconjunctivitis (VKC). Forty-four eyes of 22 patients with VKC and 44 eyes of 22 age-matched controls were studied in a hospital-based cross-sectional study. Each subject underwent a complete ophthalmological examination including slit-lamp biomicroscopy, non-invasive break-up time (NIBUT), fluorescein break-up time (FBUT), corneal fluorescein staining, and Schirmer's test. Non-contact meibography was performed using a Sirius topographer. All patients had VKC grades between 1 and 3 (Bonini scale). The mean NIBUT for cases was 8.83 ± 4.02 s and in controls, it was 15 ± 2.8 s (P value < 0.001). The mean FBUT for cases was 9.41 ± 3.45 s and in controls, it was 16.7 ± 2.5 s (P value < 0.001). Schirmer's values were 32 ± 3.1 mm in cases and 21.4 ± 4.1 mm in controls, which were significantly higher (P value < 0.001). Also, 22.72% of the cases had corneal fluorescein staining in the form of superficial punctuate keratitis, whereas none of the control groups showed corneal staining. The examination of Meibomian glands using non-contact meibography showed a mean Meibomian gland dropout in the upper lid to be 29.7 ± 14.4% in VKC cases and 10.5 ± 3.2% in controls (P value < 0.001). Meibography of the lower lid showed 25.9 ± 10.2% dropout in cases and 20.5 ± 6.1% in controls (P value = 0.004). Tear film parameters were significantly deranged in children with VKC in the active stage as compared to age-matched controls. Children with VKC also had a higher Meibomian gland dropout.

Plastic reorganization of the topological asymmetry of hemispheric white matter networks induced by congenital visual experience deprivation

Congenital blindness offers a unique opportunity to investigate human brain plasticity. The influence of congenital visual loss on the asymmetry of the structural network remains poorly understood. To address this question, we recruited 21 participants with congenital blindness (CB) and 21 age-matched sighted controls (SCs). Employing diffusion and structural magnetic resonance imaging, we constructed hemispheric white matter (WM) networks using deterministic fiber tractography and applied graph theory methodologies to assess topological efficiency (i.e., network global efficiency, network local efficiency, and nodal local efficiency) within these networks. Statistical analyses revealed a consistent leftward asymmetry in global efficiency across both groups. However, a different pattern emerged in network local efficiency, with the CB group exhibiting a symmetric state, while the SC group showed a leftward asymmetry. Specifically, compared to the SC group, the CB group exhibited a decrease in local efficiency in the left hemisphere, which was caused by a reduction in the nodal properties of some key regions mainly distributed in the left occipital lobe. Furthermore, interhemispheric tracts connecting these key regions exhibited significant structural changes primarily in the splenium of the corpus callosum. This result confirms the initial observation that the reorganization in asymmetry of the WM network following congenital visual loss is associated with structural changes in the corpus callosum. These findings provide novel insights into the neuroplasticity and adaptability of the brain, particularly at the network level.