Age-matched Healthy Participants Research Articles

A unique immune signature in blood separates therapy-refractory from therapy-responsive acute graft-versus-host disease

AbstractAcute graft-versus-host disease (aGVHD) is an immune cell‒driven, potentially lethal complication of allogeneic hematopoietic stem cell transplantation affecting diverse organs, including the skin, liver, and gastrointestinal (GI) tract. We applied mass cytometry (CyTOF) to dissect circulating myeloid and lymphoid cells in children with severe (grade III-IV) aGVHD treated with immune suppressive drugs alone (first-line therapy) or in combination with mesenchymal stromal cells (MSCs; second-line therapy). These results were compared with CyTOF data generated in children who underwent transplantation with no aGVHD or age-matched healthy control participants. Onset of aGVHD was associated with the appearance of CD11b+CD163+ myeloid cells in the blood and accumulation in the skin and GI tract. Distinct T-cell populations, including TCRγδ+ cells, expressing activation markers and chemokine receptors guiding homing to the skin and GI tract were found in the same blood samples. CXCR3+ T cells released inflammation-promoting factors after overnight stimulation. These results indicate that lymphoid and myeloid compartments are triggered at aGVHD onset. Immunoglobulin M (IgM) presumably class switched, plasmablasts, and 2 distinct CD11b– dendritic cell subsets were other prominent immune populations found early during the course of aGVHD in patients refractory to both first- and second-line (MSC-based) therapy. In these nonresponding patients, effector and regulatory T cells with skin- or gut-homing receptors also remained proportionally high over time, whereas their frequencies declined in therapy responders. Our results underscore the additive value of high-dimensional immune cell profiling for clinical response evaluation, which may assist timely decision-making in the management of severe aGVHD.

Impaired Modulation of Motor and Functional Performance in Patients after Total Knee Arthroplasty: A Prospective Observational Study.

Submaximal levels of effort are required for the performance of the most common daily tasks. Inaccuracy in modulating motor outputs during submaximal tasks has been reported as indicator of safety during daily activities in subjects with lower limb musculoskeletal disorders. The study is aimed at investigating performance modulation ability during motor and functional tasks in patients after total knee arthroplasty (TKA). Sixteen patients with end-stage osteoarthritis undergoing TKA and twenty age-matched healthy participants performed isokinetic knee extension, sit-to-stand, and walking tasks at three levels of self-estimated effort (100%, 50%, and 25%) the day before (T0) and 4 days after surgery (T1). Maximum performance in terms of peak torque (PT—knee extension), overshoot (OS—sit-to-stand), and walking speed was evaluated. Subsequently, relative error (RE) between target and observed performance was computed for the submaximal tasks (RE50% and RE25%). Our results showed a decline of maximum performance after surgery, which resulted lower in patients compared to healthy subjects. RE50% and RE25% for knee extension (involved limb) (p < 0.001) and RE25% for sit-to-stand (p < 0.001) increased from pre- to postsurgery. At T0, knee extension RE25% and walking RE50% and RE25% were higher in patients. At T1, RE50% and RE25% were higher in patients for knee extension (involved limb), sit-to-stand, and walking. In conclusion, the ability to modulate motor and functional performance decreased after TKA and resulted impaired when compared to healthy age-matched subjects. Based on relationship between ability to modulate motor outputs and risk of falling, the role of modulation ability as indicator of readiness for discharge and safe return to daily activities deserves further investigations in patients in early phase after TKA.

Optical coherence tomography angiography biomarkers of microvascular alterations in RVCL-S.

BackgroundThe brain and retina share many neuronal and vasculature characteristics. We investigated the retinal microvasculature in patients with a monogenic vasculopathy using optical coherence tomography angiography (OCTA). OCT-A is a novel precise non-invasive imaging method that may provide biomarkers suitable for diagnosis and follow-up of small vessel diseases.MethodsIn this exploratory cross-sectional study, eleven RVCL-S patients and eleven age-matched healthy control participants were included. The size of the foveal avascular zone (FAZ) and the vascular density of the superficial capillary networks in the retina were measured by OCT-A.ResultsThe symptomatic and presymptomatic patients showed significantly lower vascular density values than controls in the foveal region [median (IQR) 18.2% (15.8–18.6) vs. 24.4% (21.5–26.8) (p < 0.001), 29.8% (29.6–30.8) vs. 33.2% (32.0–33.6) (p = 0.002), respectively]. The FAZ was significantly larger in the symptomatic RVCL-S patients than in the control group [13,416 square pixels [7,529–22,860] vs. 1,405 square pixels [1,344–2,470] (p < 0.001)]. No significant difference was identified in measurements of FAZ comparing presymptomatic and controls.ConclusionOur findings with OCT-A demonstrated that RVCL-S causes an increase in the size of the FAZ in symptomatic RVCL-S patients compared to healthy participants. Moreover, there is a decrease in vessel density in the superficial capillary networks in both symptomatic and presymptomatic patients. In the future, newly developed precise objective instruments such as OCT (-A) may provide important tools in determining disease activity for follow up of common small vessel diseases.

Inflammation-related Gene Polymorphisms Associated With Childhood Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is a malignant hematological disease and is often accompanied by a variety of genetic abnormalities. The pathogenesis of inflammation-related single-nucleotide polymorphism (SNP) in children with ALL remains unclear. This study was to discover the association of the SNP sites of some inflammation-related genes and the susceptibility and treatment response of ALL in children, so as to provide personalized treatment for ALL in children. One hundred sixty-five childhood ALL patients and 175 age-matched healthy participants were recruited in this study. We investigated the involvement of 31 SNPs of the inflammation-related genes in the pathogenesis and treatment response of childhood ALL. Statistical analysis revealed that rs2280714 in IRF5, rs2297630 in SDF-1, rs4353135 in NLRP3, rs1946518 in interleukin-18 were related to the susceptibility to pediatric ALL. Interleukin-1β rs16944 SNP was correlated with ALL risk stage in children. Rs7633631 in CD226 and rs10818488 in TRAF1 were related to the minimal residual disease (MRD) on day 15 and day 33. Certain SNPs of inflammation genes were associated with the susceptibility and treatment response of ALL children. These findings may help in the early detection, diagnostic evaluation, and making individual chemotherapy regimen for ALL children according to the genotype of these sites at the time of initial diagnosis.

The Value of Insulin Resistance indices For detecting Insulin Resistance in Polycystic Ovarian Syndrome Patients

Polycystic Ovarian Syndrome (PCOS) is characterized by increased ovarian and androgen hormone secretion. Patients with PCOS are said to be at high risk for insulin resistance(IR). IR is a sign of PCOS that comprises impaired glucose tolerance and elevated insulin production. HOMA-IR is a test that assesses insulin resistance by measuring blood glucose and insulin levels. There are other indexes that are also available for determining IR such as the quantitative insulin sensitivity check index(QUICKI) and McAuley index. Hence, in this study HOMA-IR, QUICKI and McAuley index were used to determine the IR among PCOS individuals. This case-control cross sectional study included 62 participants between the age group of 20-40 years. They were divided into two groups such as Group B which includes 31 PCOS patients diagnosed based on Rotterdam criteria and Group A includes 31 healthy age-matched female participants. After obtaining informed consent, fasting blood sample was collected from all the participants. Based on the analyzed biochemical parameters IR was assessed using HOMA-IR, QUICKI and McAuley index. For statistical analysis student t-test, ROC curve and bivariate regression analysis were done. In this study, it is observed that an increase in BMI was at a higher risk of developing PCOS. It is seen that fasting glucose, insulin and lipid profile (except HDL-C) were significantly elevated in PCOS individuals. The HOMA-IR was significantly increased and QUICKI and McAuley’s index were significantly decreased in PCOS which shows that PCOS patients are at higher risk of developing IR. Crude odds were calculated which shows that increase in HOMA-IR levels has an 86.25% increase risk of developing IR in PCOS patients when compared with the other indexes.HOMA-IR has a higher predictor % of developing IR in PCOS individuals, but still QUICKI and McAuley index can also be used as a predictor of risk.

Alcohol use disorder-associated structural and functional characteristics of the insula.

Based on our current understanding of insular regions, effects of chronic alcohol use on the insula may affect the integration of sensory-motor, socio-emotional, and cognitive function. There is no comprehensive understanding about these differences in individuals with alcohol use disorder that accounts for both structural and functional differences related to chronic alcohol use. The purpose of this study was to investigate these variations in both the anterior and posterior insula in persons with alcohol use disorder. We investigated insula gray matter volume, morphometry, white matter structural connectivity, and resting state functional connectivity in 75 participants with alcohol use disorder (females=27) and 75 age-matched healthy control participants (females=39). Results indicated structural differences mostly in the anterior regions, while functional connectivity differences were observed in both the anterior and posterior insula in those with alcohol use disorder. Differing connectivity was observed with frontal, parietal, occipital, cingulate, cerebellar, and temporal brain regions. While these results align with prior studies showing differences primarily in anterior insular regions, they also contribute to the existing literature suggesting differences in anterior insular connectivity with brain regions shown to be engaged during higher cognitive and emotional tasks.

Resting-state electroencephalography changes in poststroke patients with visuospatial neglect.

BackgroundThis study aimed to explore the electrophysiological characteristics of resting-state electroencephalography (rsEEG) in patients with visuospatial neglect (VSN) after stroke.MethodsA total of 44 first-event sub-acute strokes after right hemisphere damage (26 with VSN and 18 without VSN) were included. Besides, 18 age-matched healthy participants were used as healthy controls. The resting-state electroencephalography (EEG) of 64 electrodes was recorded to obtain the power of the spectral density of different frequency bands. The global delta/alpha ratio (DAR), DAR over the affected hemispheres (DARAH), DAR over the unaffected hemispheres (DARUH), and the pairwise-derived brain symmetry index (pdBSI; global and four bands) were compared between groups and receiver operating characteristic (ROC) curve analysis was conducted. The Barthel index (BI), Fugl-Meyer motor function assessment (FMA), and Berg balance scale (BBS) were used to assess the functional state of patients. Visuospatial neglect was assessed using a battery of standardized tests.ResultsWe found that patients with VSN performed poorly compared with those without VSN. Analysis of rsEEG revealed increased delta and theta power and decreased alpha and beta power in stroke patients with VSN. Compared to healthy controls and poststroke non-VSN patients, patients with VSN showed a higher DAR (P < 0.001), which was significantly positively correlated with the BBS (DAR: r = –0.522, P = 0.006; DARAH: r = –0.521, P = 0.006; DARUH: r = –0.494, P = 0.01). The line bisection task was positively correlated with DAR (r = 0.458, P = 0.019) and DARAH (r = 0.483, P = 0.012), while the star cancellation task was only positively correlated with DARAH (r = 0.428, P = 0.029). DARAH had the best discriminating value between VSN and non-VSN, with an area under the curve (AUC) of 0.865. Patients with VSN showed decreased alpha power in the parietal and occipital areas of the right hemisphere. A higher parieto-occipital pdBSIalpha was associated with a worse line bisection task (r = 0.442, P = 0.024).ConclusionrsEEG may be a useful tool for screening for stroke patients with visuospatial neglect, and DAR and parieto-occipital pdBSIalpha may be useful biomarkers for visuospatial neglect after stroke.

The Psychopathology of Worthlessness in Depression.

BackgroundDespite common dissatisfaction with the syndromic heterogeneity of major depression, investigations into its symptom structure are scarce. Self-worthlessness/inadequacy is a distinctive and consistent symptom of major depression across cultures.AimsWe investigated whether self-worthlessness is associated with self-blaming attribution-related symptoms or is instead an expression of reduced positive feelings overall, as would be implied by reduced positive affect accounts of depression.Methods44,161 undergraduate students in Study 1, and 215 patients with current Major Depressive Disorder (MDD) and 237 age-matched healthy control participants in Study 2 completed the well-validated Symptom Check List-90. Depression-relevant items were used to construct regularized partial correlation networks with bootstrap estimates of network parameter variability.ResultsWorthlessness co-occurred more strongly with other symptoms linked to self-blaming attributions (hopelessness, and self-blame), displaying a combined edge weight with these symptoms which was significantly stronger than the edge weight representing its connection with reduced positive emotion symptoms (such as reduced pleasure/interest/motivation, difference in edge weight sum in Study 1 = 2.95, in Study 2 = 1.64; 95% confidence intervals: Study 1: 2.6–3.4; Study 2: 0.02–3.5; Bonferroni-corrected p < 0.05).ConclusionsThis confirms the prediction of the revised learned helplessness model that worthlessness is most strongly linked to hopelessness and self-blame. In contrast, we did not find a strong and direct link between anhedonia items and a reduction in self-worth in either study. This supports worthlessness as a primary symptom rather than resulting from reduced positive affect.

Magnetic resonance imaging assessment of juvenile idiopathic arthritis using OMERACT and EuroTMjoint classifications

This retrospective case–control study compared inflammatory and structural damage in the temporomandibular joint of patients with juvenile idiopathic arthritis (JIA) and its subtypes and healthy patients using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) and EuroTMjoint classifications. Correlations between the scores of the two classifications and time of diagnosis were evaluated. Twenty-nine JIA patients and 48 age-matched healthy participants were examined. TMJ images on each side were considered individually. Oligoarticular and polyarticular subtypes were present in 44.8% and 55.2% of patients, respectively. The JIA group presented a higher frequency and more severe signs of inflammatory and structural changes (P < 0.05), except for effusion (P = 0.83). The polyarticular subtype showed a higher change intensity. The time of JIA diagnosis was not correlated with inflammatory and structural changes. Positive correlations between inflammation and bone deformity scores were observed for the EuroTMjoint classification (r = 0.462, P < 0.001; low correlation) and OMERACT classification (r = 0.737, P < 0.001; high correlation). Positive correlations between the OMERACT and EuroTMjoint classifications were found for inflammation score (r = 0.907, P < 0.001; very high correlation) and bone deformity score (r = 0.854, P < 0.001; high correlation). Both classifications showed a higher frequency and intensity of inflammation and bone deformity in JIA patients. The results of this study suggest that the appropriate management of inflammation may reduce the potential for structural damage to the TMJ.

Macular Vessel Density Measurement in Pediatric Renal and Liver Transplant

Microcirculatory dysfunction is known to be associated with organ failure and increased mortality in transplant patients. Noninvasive monitorization of retinal structures of the eye could be a predictor for systemic microvasculature in these patients. Therefore, in this study we aimed to evaluate the retinal microvascular changes in pediatric patients who had undergone liver or renal transplant surgery, using optical coherence tomography angiography. The medical records of pediatric patients who had liver or renal transplant in the past 10 years were reviewed. The macular vessel density parameters were obtained by optical coherence tomography angiography (Avanti RTVue XR). The results were compared with the age-matched, sex-matched, and spherical equivalent-matched healthy participants (control group). The IBM SPSS (version 25.0) statistics program was used for data analysis. We included 32 eyes of 16 liver transplant patients, 20 eyes of 10 renal transplant patients, and 64 eyes of 32 healthy participants (control group). Superficial macular whole image, superficial perifoveal, and deep foveal vessel densities were found to be lower in the liver transplant group compared with the healthy control group (P = .02, P = .01, and P = .01, respectively). Superficial foveal, deep macular whole image, deep foveal, and deep perifoveal vessel densities were found to be lower in the renal transplant group compared with the healthy control group (P = .03, P = .04, P = .01, and P = .02, respectively). Macular vessel density measurements are affected in pediatric renal and liver transplant patients. In those patients, retinal optical coherence tomography and optical coherence tomography angiography measurements may provide a noninvasive window to the microcirculation.

HDAC3 single-nucleotide polymorphism rs2530223 is associated with increased susceptibility and severity of primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder characterized by a low platelet count and increased risk of bleeding. We previously reported that low-dose chidamide, a histone deacetylase (HDAC) inhibitor, restores immune tolerance in patients with ITP. This study aimed to evaluate the association of a single-nucleotide polymorphism (SNP) rs2530223 in the HDAC3 gene with susceptibility to ITP and its clinical features. Patients with ITP and age-matched healthy participants were recruited for this case-control study. Genotyping of the HDAC3 rs2530223 polymorphism was performed using MassARRAY platform. Individuals with T allele of HDAC3 rs2530223 exhibited a 1.472-fold increased risk of ITP susceptibility (OR 1.472; 95% CI 1.100-1.969; p=.009), while ones with the TT genotype under the codominant and recessive models, and the TC/TT genotypes under the dominant model all revealed increased risk of ITP susceptibility (dominant odds ratio[OR] 1.965; 95% CI: 1.046-3.656; p=.036; codominant OR 2.264; 95% CI 1.175-4.360; p=.015; and recessive OR 1.512; 95% CI 1.028-2.224; p=.036, respectively). Regarding platelet counts in ITP patients, we observed that the TC/TT genotypes exhibited a 3.932-fold increased risk for platelet (PLT) <30 × 109 /L (OR 3.932; 95% CI 1.426-10.842; p=.008). This study indicates that HDAC3 rs2530223 may be an important genetic factor related to ITP susceptibility and platelet count in ITP patients, providing new perspectives on disease progression, new therapeutic targets, and severity prediction.

Clinical Outcomes of Minimally Invasive Corneal Neurotization After Cerebellopontine Angle Neurosurgical Procedures

PurposeTo report 12 patients with neurotrophic keratopathy due to the trigeminal nerve injury after intracranial tumor surgeries underwent minimally invasive corneal neurotization and evaluate the outcomes of corneal reinnervation.MethodsTwelve patients (12 eyes) with neurotrophic keratopathy caused by the trigeminal nerve injury after intracranial surgeries received minimally invasive corneal neurotization. All the preoperative central corneal sensation was under 5 mm, and minimally invasive corneal neurotization was performed over 6 months after the intracranial surgery. Follow-up was conducted 1 week and 1 month after the surgery and then every 3 months. Twelve healthy age-matched participants were enrolled as controls. The indicators included corneal sensation, best-corrected visual acuity, corneal nerve fiber length and branch density, diameter of nerve trunk, corneal ulcer lesion ratio, and sensation of the contralateral forehead.ResultsMean follow-up was 24.7 ± 7.1 months. Mean central corneal sensation rose from 0.4 ± 1.4 to 31.7 ± 21.8 mm. Corneal nerve fiber length improved from 9.56 ± 5.00 to 14.96 ± 4.65 mm/mm2 and corneal nerve branch density and diameter of nerve trunk both increased (p < .01 and p < .05, respectively). Corneal lesion ratio decreased from 0.17 ± 0.12 to 0.10 ± 0.10 (p < .01).ConclusionsMinimally invasive corneal neurotization promotes corneal reinnervation for patients with neurotrophic keratopathy induced by the trigeminal nerve injury after intracranial surgeries. The process of corneal reinnervation after minimally invasive corneal neurotization often lasts over 12 months, and it takes about 18 months to return to a higher level. Corneal sensation and corneal nerve fiber length are related to clinical outcomes such as corneal ulcer lesion and best-corrected visual acuity. The effect on the sensation of the contralateral side forehead is temporary, and most patients can restore normal forehead sensation of the contralateral side.

Cervical Vertebral Height Approximates Hyoid Displacement in Videofluoroscopic Images of Healthy Adults.

Clinicians and researchers commonly judge the completeness of hyoid displacement from videofluoroscopic swallow study (VFSS) videos. Judgments made during the clinical exam are often subjective, and post-examination analysis reduces the measure's immediate value. This study aimed to determine the validity and feasibility of a visual, anatomically scaled benchmark for judging complete hyoid displacement during a VFSS. The third and fourth cervical vertebral bodies (C3 and C4) lie at roughly the same vertical position as the hyoid body and are strongly correlated with patient height. We hypothesized that anterior and superior displacement of the hyoid bone would approximate the height of one C3 or C4 body during safe swallows. Trained raters marked points of interest on C3, C4, and the hyoid body on 1414 swallows of adult patients with suspected dysphagia (n = 195) and 50 swallows of age-matched healthy participants (n = 17), and rated Penetration Aspiration Scale scores. Results indicated that the mean displacements of the hyoid bone were greater than one C3 unit in the superior direction for all swallows from patient and healthy participants, though significantly and clinically greater in healthy participant swallows (p < .001, d > .8). The mean anterior and superior displacements from patient and healthy participant swallows were greater than one C4 unit. Results show preliminary evidence that use of the C3 and/or C4 anatomic scalars can add interpretive value to the immediate judgment of hyoid displacement during the conduct of a clinical VFSS examination.

Investigating the utility of saliva immunoglobulins for the detection of myeloma and using myeloma proteins to clarify partition between oral and systemic immunity.

ObjectivesMyeloma is characterised by the presence of monoclonal immunoglobulin (M‐protein) and the free light chain (FLC) in blood. We investigated whether these M‐proteins and FLC are detectable in myeloma patients’ saliva to evaluate its utility for non‐invasive screening and monitoring of haematological malignancies.MethodsA total of 57 patients with monoclonal gammopathy and 26 age‐matched healthy participants provided paired serum and saliva samples for immunoglobulin characterisation and quantification.ResultsMyeloma patients had IgG or IgA M‐protein levels ranging up to five times and FLC levels up to a thousand times normal levels of polyclonal immunoglobulins. Despite these highly elevated levels, only two IgG and no IgA M‐proteins or FLC could be detected in paired saliva samples. Most patients had reduced levels of serum polyclonal immunoglobulins, but all had normal levels of salivary IgA.ConclusionsImmunoglobulin transfer from blood is not determined by levels in the systemic circulation and more likely dictated by periodontal inflammation and the integrity of the oral epithelium. Immunoglobulins secreted by bone marrow plasma cells do not substantially enter saliva, which represents a poor medium for myeloma diagnosis. These findings, along with normal salivary IgA levels despite systemic immunoparesis, support a strong partitioning of oral from systemic humoral immunity.

Retinal microvascular changes in white matter hyperintensities investigated by swept source optical coherence tomography angiography

BackgroTo assess the microvascular changes in the macular region and the foveal avascular zone (FAZ) area in participants with white matter hyperintensities (WMHs) using swept source optical coherence tomography angiography (SS OCTA).MethodsThis cross-sectional study included a total of 23 WMH participants (45 eyes) and 20 age-matched healthy participants (40 eyes). SS OCTA (VG200; SVision Imaging, Ltd., Luoyang, China) was used to assess the retinal vessel density (VD) and the FAZ area. VD was measured in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) within a 6 × 6-mm scan centred on the macula using a 5-mm Macula circle. The FAZ area was automatically measured on the inner retina layer within a 3 × 3-mm scan in the macular region.ResultsThere was no significant difference in VD in the SVP between the two groups. However, VD in both the ICP and DCP was significantly decreased in WMH participants (P = 0.028, P = 0.016). The FAZ area was significantly enlarged in WMH participants (P = 0.030). The signal quality was significantly lower in WMH participants (P < 0.001).ConclusionsThis study suggested that WMH participants have retinal microvascular and foveal avascular zone area changes compared with healthy controls. Further longitudinal studies with larger sample sizes are warranted to identify the value of our findings in the early evaluation of WMHs.

Effects of osteopathic manipulative treatment vs. osteopathic cranial manipulative medicine on Parkinsonian gait.

Sixty thousand people are diagnosed with Parkinson's disease (PD) each year, making it the second most common neurodegenerative disorder. PD results in a variety of gait disturbances, including muscular rigidity and decreased range of motion (ROM), that increase the fall risk of those afflicted. Osteopathic manipulative treatment (OMT) emphasizes the central role of the musculoskeletal system, which could be ideal for addressing the somatic dysfunction associated with neurodegeneration in PD. The close anatomical relationship of structures implicated in PD within the skull and the increased frequency of strain patterns raise the question of whether osteopathic cranial manipulative medicine (OCMM) can improve gait performance by improving circulation to the affected nervous tissue. However, there have been few studies in recent years that explore the effects of a standardized OMT protocol on Parkinsonian gait characteristics, and there have been few studies that include OCMM techniques. This study aims to determine whether a single session of OMT or OMT+OCMM can improve the gait of individuals with PD by addressing joint restrictions in the sagittal plane and by increasing ROM in the lower limb. The following study is a two-group, randomized controlled trial in which individuals with PD (n=45) and age-matched healthy control participants (n=45) were recruited from the community. PD participants were included if they were otherwise healthy, able to stand and walk independently, had not received OMT or physical therapy (PT) within 30days of data collection, and had idiopathic PD in Hoehn and Yahr stages 1.0-3.0. PD participants were randomly assigned to one of three experimental treatment protocols: a 'whole-body' OMT protocol (OMT-WB), which included OMT and OCMM techniques; a 'neck-down' OMT protocol (OMT-ND), including only OMTtechniques; and a sham treatment protocol. Control participants were age-matched to a PD participant and were provided the same OMT experimental protocol. An 18-camera motion analysis system was utilized to capture 3-dimensional (3D) position data in a treadmill walking trial before and after the assigned treatment protocol. Pretreatment and posttreatment hip, knee, and ankle ROM were compared with paired t-tests, and joint angle waveforms during the gait cycle were analyzed with statistical parametric mapping (SPM), which is a type of waveform analysis. Individuals with PD had significantly reduced hip and knee extension in the stance phase compared to controls (32.9-71.2% and 32.4-56.0% of the gait cycle, respectively). Individuals with PD experienced a significant increase in total sagittal hip ROM (p=0.038) following a single session of the standardized OMT-WB treatment protocol. However, waveform analysis found no significant differences in sagittal hip, knee, or ankle angles at individual points of the gait cycle following OMT-WB, OMT-ND, or sham treatment protocols. The increase in hip ROM observed following a single session of OMT-WB suggests that OCMM in conjunction with OMT may be useful for improving gait kinematics in individuals with PD. Longitudinal studies over multiple visits are needed to determine the long-term effect of regular OMT and OMT+OCMM treatments on Parkinsonian gait characteristics.

Deficient Interhemispheric Connectivity Underlies Movement Irregularities in Parkinson’s Disease

Movement execution is impaired in patients with Parkinson's disease. Evolving neurodegeneration leads to altered connectivity between distinct regions of the brain and altered activity at interconnected areas. How connectivity alterations influence complex movements like drawing spirals in Parkinson's disease patients remains largely unexplored. We investigated whether deteriorations in interregional connectivity relate to impaired execution of drawing. Twenty-nine patients and 31 age-matched healthy control participants drew spirals with both hands on a digital graphics tablet, and the regularity of drawing execution was evaluated by sample entropy. We recorded resting-state fMRI and task-related EEG, and calculated the time-resolved partial directed coherence to estimate effective connectivity for both imaging modalities to determine the extent and directionality of interregional interactions. Movement performance in Parkinson's disease patients was characterized by increased sample entropy, corresponding to enhanced irregularities in task execution. Effective connectivity between the motor cortices of both hemispheres, derived from resting-state fMRI, was significantly reduced in Parkinson's disease patients in comparison to controls. The connectivity strength in the nondominant to dominant hemisphere direction in both modalities was inversely correlated with irregularities during drawing, but not with the clinical state. Our findings suggest that interhemispheric connections are affected both at rest and during drawing movements by Parkinson's disease. This provides novel evidence that disruptions of interhemispheric information exchange play a pivotal role for impairments of complex movement execution in Parkinson's disease patients.

Neural correlates of impaired response inhibition in the antisaccade task in Parkinson’s disease

Deficits in response inhibition are a central feature of the highly prevalent dysexecutive syndrome found in Parkinson’s disease (PD). Such deficits are related to a range of common clinically relevant symptoms including cognitive impairment as well as impulsive and compulsive behaviors.In this study, we explored the cortical dynamics underlying response inhibition during the mental preparation for the antisaccade task by recording magnetoencephalography (MEG) and eye-movements in 21 non-demented patients with early to mid-stage Parkinson’s disease and 21 age-matched healthy control participants (HC).During the pre-stimulus preparatory period for antisaccades we observed:•a preparation-related increase in beta band activity in the right dorsolateral prefrontal cortex (DLPFC) of HC (n = 15) for antisaccades compared with prosaccades that was not detectable in the PD group (n = 17);•a significant attenuation of the preparation-related increase in alpha band power in bilateral FEF and reduced alpha band connectivity between the right DLPFC and right FEF in the PD group compared with HC, suggesting reduced top-down control to inhibit pre-potent activation of FEF in PD; and•a positive correlation between the magnitude of pre-stimulus beta desynchronization in FEF and subsequent antisaccade latency in PD and HC, indicating a relationship between preparatory beta band modulation and effectiveness of subsequent antisaccade execution.Taken together, the results indicate that alterations in pre-stimulus prefrontal alpha and beta activity hinder proactive response inhibition and in turn result in higher error rates and prolonged response latencies in PD.

Correlation between Myocardial Iron Overload Detected by CMRT2* and Left Ventricular Function Assessed by Tissue Doppler Imaging in Patients with Thalassemia Major.

Background:Iron overload and cardiac dysfunctions are common complications in patients with thalassemia major (TM). Different imaging methods can be used to detect ventricular dysfunction in these patients. In this study, we aim to understand the value of tissue Doppler imaging (TDI) in the detection of myocardial dysfunction in patients with TM who have been diagnosed with iron overload using cardiovascular magnetic resonance CMRT2*.Methods:In this cross-sectional study, fifty patients with TM diagnosed with iron overload who had no clinical signs and symptoms of cardiac dysfunction were chosen as a case group. The control group included fifty sex- and age-matched healthy participants without a history of cardiac and hematological diseases. TDI, pulsed wave Doppler (PWD), and standard echocardiography were performed to study the left ventricular function, and cardiac iron overload assessed by CMRT2*. Then, the patients with TM were divided into two subgroups and compared with each other. Group 1a includes individuals with T2* value <20 ms and group 1b T2* value >20 ms.Results:There was no significant difference between the standard echocardiography results and PWD parameters of the case and control groups; however, CMRT2* findings and TDI parameters were different between the case and control groups. CMRT2* findings also were not correlated with PWD parameters. In group 1a, CMRT2* findings were negatively correlated with age, E', A', early deceleration time, and isovolumetric relaxation time and positively correlated with E/E' ratio. Finally, PWD and TDI parameters were significantly different between the two subgroups.Conclusion:TDI can detect ventricular systolic and diastolic dysfunctions in earlier stages among patients with iron overload. It seems that TDI could detect abnormalities more accurately, and it is better to consider subclinical cardiac dysfunction in patients with even CMRT2* value of more than 20 ms and reevaluate them in future.

Association of immune abnormalities with symptom severity in Egyptian autistic children

Background Autism spectrum disorder (ASD) is considered a spectrum of behavioral anomalies described by having impaired social interaction and communication. It is usually accompanied by repetitive and stereotyped behavior. ASD likely develops from a combination of genetic and environmental factors. Among suggestions, one has been persistently proposed where an immune dysfunction was related to certain forms of ASD. Growing evidence of autoimmune phenomena in patients with ASD may represent the occurrence of changed or perhaps unsuitable immune responses in this disorder.Objectives This study was aimed to evaluate cell-mediated as well as humoral immunity in children with ASD. This was through evaluation of lymphocyte count (CD3, CD16, and CD19) and estimation of the serum immunoglobulin levels (IgG, IgM, and IgA).Patients and methods This study was carried out in the National Research Centre. A total of 50 newly diagnosed children with ASD were included (33 males and 17 females), with an age range from 3 to 8 years, in addition to 50 apparently healthy age-matched and sex-matched participants as a control group. CD3, CD16, and CD19 were estimated using flow cytometry. Serum Ig levels were measured using immunonephelometry.Results and conclusion The study results revealed that children with autism had significantly lower CD19 in comparison with the control group (P<0.001). Autistic children also had considerably higher numbers of CD16 (P<0.001) and significant increased absolute lymphocyte count (P=0.034) in comparison with healthy controls. CD3% and absolute CD16 count were significantly positive correlated with Childhood Autism Rating Scale score in children with ASD (P=0.004 and 0.025, respectively). An increased total lymphocyte and natural killer cell count together with decreased B lymphocyte count and positive correlations in CD3 and absolute CD16 count with Childhood Autism Rating Scale score in participants with ASD revealed the impaired cell-mediated immunity in participants with ASD, and these tests might be useful as diagnostic markers for ASD and its degree of severity.