Involvement In Early Stages Research Articles

Clinical manifestations, treatment and prognosis of juvenile idiopathic arthritis with pulmonary involvement in China: a single centre study.

In recent years, the distinct clinical presentations and elevated mortality rates of various subtypes of juvenile idiopathic arthritis (JIA) with pulmonary involvement have garnered significant attention. This study aimed to elucidate the clinical characteristics of pulmonary involvement in patients with JIA to improve clinicians' knowledge. This single-centre retrospective study analysed the baseline data, treatment options, follow-up of sixty patients of JIA with pulmonary involvement in China. Patients with interstitial lung disease (ILD) were further classified in accordance with the 2013 American Thoracic Society/European Respiratory Society International multidisciplinary consensus on idiopathic interstitial pneumonia. Sixty patients (5.03%) with JIA were complicated with pulmonary involvement. The highest subtype was systemic JIA (sJIA, 63.3%), followed by rheumatoid factor (RF)-positive polyarthritis (pJIA, 25.0%). The incidence of macrophage activation syndrome (MAS) was 21.6%. The most common diagnosis was ILD (90%). Respiratory symptoms/signs were initially experienced by 61.7% of the patients, and respiratory support was required by 21.7%. High-resolution CT classification of sJIA revealed non-specific interstitial pneumonia (NSIP) and organising pneumonia. High-resolution CT classification of pJIA was NSIP and usually interstitial pneumonia (UIP). Patients were treated with NSAIDs, along with glucocorticoids, DMARDs, and biological agents. The survival rates after 1 and 5 years were approximately 93.3% and 90.0%, respectively. Patients with JIA with pulmonary involvement present with early onset, high mortality rate. JIA patients should undergo physical examination thoroughly and high-resolution CT scans, lung function tests for evaluating and monitoring the occurrence and development of pulmonary involvement in early stages to improve prognosis.

37 Assessment of Social Cognition in Patients with Multiple Sclerosis

Objective:Multiple sclerosis (MS) is a persistent neuroinflammatory disease of the central nervous system that affects young adults, and is pathologically characterized by multiple and distributed focal white matter lesions, although they are characteristically located in periventricular regions. Cognitive impairment occurs in all clinical forms of the disease, with great variability and great impact on the quality of life of patients. Recent research indicates that in addition to cognitive and physical deficits, they also have deficits in social cognition, such as Theory of Mind. Although social cognition in patients with multiple sclerosis has begun to be studied in recent years, there is still little knowledge about its impact in the early stages of the disease, when the load of injuries is low and physical disability is not yet present. A series of 7 cases of patients diagnosed with MS in follow-up by the Multiple Sclerosis polyclinic of the Institute of Neurology of the Hospital de Clínicas is presented.Participants and Methods:Clinically stable patients with no recent urges and no cognitive complaint were included. They were evaluated with the ACE-R screening test and Theory of Mind tests: Reading the mind in the eyes and Faux Pas tests.Results:All patients presented normal ACE results, without indicators of cognitive impairment and poor performance in the emotion reading test. In two cases, poor yields in Faux Pas were also found.Conclusions:Social cognition has a great impact on quality of life, and there are indicators of involvement in early stages of the disease in which other typical cognitive deficits are not yet evident, and may constitute the first indicator of deterioration. The evaluation and early detection of deficits in social cognition could contribute to the treatment and quality of life of patients.

HUMAN CENTERED DESIGN TO DEVELOP A LGBTQ+ COMMUNITY ADVISORY BOARD FOR SKILLED NURSING FACILITIES

Abstract Lesbian, gay, bisexual, transgender, queer (LGBTQ+) adults will require inclusive skilled nursing care as they age, but there is a paucity in LGBTQ+ specific training resources for skilled nursing facility (SNF) healthcare workers. Development of community advisory boards is becoming common in research studies as funders place emphasis on stakeholder engagement, but how advisory boards are created with community member involvement at the onset remains less clear. This presentation describes the creation of a community advisory board of LGBTQ+ community members, community organizations, and SNF administrators that work together to develop LGBTQ+ resources for 25 SNFs. Advisory board members were identified using a design thinking framework and the Field Guide to Human-Centered Design. Potential board members were identified through networking with community-based organizations, existing relationships with SNFs, and by word of mouth. The advisory board consists of 3 LGBTQ+ adults, 4 SNF administrators, 1 AARP community outreach and advocacy associate director, 1 advocacy coordinator for LGBTQ+ older adults, 1 SNF physician liaison, and 1 nurse scientist. To gain buy-in, individual interviews and focus groups with potential advisory board members were conducted. Meetings provided an opportunity to describe project goals and how potential member’s expertise would guide development of resources. LGBTQ+ adult community members received compensation for their participation. The advisory board is meeting monthly and approaching the design phase. Community stakeholder involvement in early stages of development will help ensure that LGBTQ+ resources are relevant and applicable to enhance health and well-being of LGBTQ+ older adults in the future.

Identification of Leukocyte Surface P2X7 as a Biomarker Associated with Alzheimer's Disease.

Alzheimer’s disease (AD) has shown altered immune responses in the periphery. We studied P2X7 (a proinflammatory receptor and a scavenger receptor) and two integrins, CD11b and CD11c, on the surface of circulating leukocytes and analysed their associations with Aβ-PET, brain atrophy, neuropsychological assessments, and cerebrospinal fluid (CSF) biomarkers. Total 287 age-matched, sex-balanced participants were recruited in a discovery cohort and two validation cohorts through the AIBL study and studied using tri-colour flow cytometry. Our results demonstrated reduced expressions of P2X7, CD11b, and CD11c on leukocytes, particularly monocytes, in Aβ +ve cases compared with Aβ −ve controls. P2X7 and integrin downregulation was observed at pre-clinical stage of AD and stayed low throughout disease course. We further constructed a polygenic risk score (PRS) model based on 12 P2RX7 risk alleles to assess the genetic impact on P2X7 function in AIBL and ADNI cohorts. No significant association was identified between the P2RX7 gene and AD, indicating that P2X7 downregulation in AD is likely caused by environmental changes rather than genetic factors. In conclusion, the downregulation of P2X7 and integrins at pre-clinical stage of AD indicates altered pro-inflammatory responses, phagocytic functions, and migrating capabilities of circulating monocytes in early AD pathogenesis. Our study not only improves our understanding of peripheral immune involvement in early stage of AD but also provides more insights into novel biomarker development, diagnosis, and prognosis of AD.

NERVE CONDUCTION STUDIES IN ASYMPTOMATIC HIV POSITIVE PERSONS

Background: Nerve Conduction Studies were performed in asymptomatic HIV positive persons and corresponding controls to detect subclinical peripheral nervous system involvement in early stage of HIV. Aims & Objective: To perform Nerve Conduction Studies in asymptomatic HIV positive persons and corresponding controls. Material and Methods: In this study,100 participants in the age group 25-45 years were selected. In study group, 50 3 participants who were HIV positive and asymptomatic (CD4 count > 350 cells/mm ) and were not on Anti Retro Viral Treatment (ART),were included.In control group 50 healthy age matched HIV negative participants were included.We performed Nerve Conduction Studies in these participants. For motor nerves, Distal Latency (DL), Motor Nerve Conduction Velocity (MNCV), Compound Muscle Action Potential (CMAP) amplitude were measured and for sensory nerves Onset Latency (OL), Sensory Nerve Conduction Velocity (SNCV) and Sensory Nerve Action Potential (SNAP) amplitude were measured. Results: Nerve Conduction Studies in asymptomatic HIV revealed that,MNCV was significantly decreased for median motor nerve and tibial motor nerve in study group compared to control group, SNAP was significantly reduced for median sensory nerve in study group compared to control group,OL was significantly prolonged for sural nerve in study group than control group and SNCV was significantly decreased for sural nerve in study group than control group. Conclusion: Nerve Conduction Studies in asymptomatic HIV positive persons suggests subclinical peripheral nervous system involvement in early stages of HIV. Hence Nerve Conduction Studies can be important to detect subclinical peripheral nervous system involvement in the early stages of HIV.

Sudomotor and cardiovascular autonomic function in de novo Parkinson's disease assessed by sudoscan and cardiovascular reflexes

The prevalence of autonomic involvement in early stage of Parkinson ‘s disease (PD) is still debated. Aim of this study is to assess the autonomic functions in de novo PD patients (dnPD) in comparison with PD patients on therapy (PDot) and healthy controls (HC).

Evaluation of S-100 immunostaining in the demonstration of nerve changes in tuberculoid and borderline tuberculoid leprosy - A descriptive, prospective and retrospective analytical study

S-100 immunohistochemical staining may detect nerve involvement in early stages of tuberculoid spectrum of leprosy. This study investigated the use of S-100 in early diagnosis of the tuberculoid and borderline tuberculoid leprosy and compared its sensitivity with hematoxylin and eosin (HE) stains in discerning the nerve involvement.To study the different histopathological patterns of nerve involvement in tuberculoid and borderline tuberculoid leprosy on S-100 immunostaining and also to compare the sensitivity of HE stain with S-100 immunostain in discerning the nerve involvement in these cases.This was a descriptive, prospective and retrospective analytical study, which included patients with tuberculoid spectrum of leprosy. Histopathological examination (HPE) and immunohistochemical (IHC) analysis were performed on all skin biopsies using HE stain and S-100 immunostain, respectively. Then the sensitivities of both the stains in discerning the nerve involvement were calculated and the data was analyzed using SPSS software version 22 by applying chi-square test.The study included a total of 58 patients [tuberculoid (n=28), borderline tuberculoid (n=30)]. The mean age was 43 yrs. The most common clinical manifestation was hypopigmented patches (n=40, 70%) with loss of sensation (n=39, 68.3%). HPE revealed 36 cases with well-defined granulomas, 22 cases with ill-defined granulomas and 41 cases with nerve destruction. IHC analysis showed four different patterns of nerve damage (fragmented, n=32; infiltrated and fragmented, n=14; infiltrated, n=10; intact, infiltrated and fragmented; n=1). The sensitivity and positive predictive value (PPV) of HE staining in delineating the nerve involvement were 68.96% and 100%, respectively. Whereas, the sensitivity and PPV of S-100 IHC were 100% each.Less number of cases.Use of S-100 IHC along with HPE aids in early, accurate and confirmatory diagnosis.

Sudomotor and cardiovascular autonomic function in de novo Parkinson's disease assessed by sudoscan and cardiovascular reflexes

ObjectiveThe prevalence of autonomic involvement in early stage of Parkinson ‘s disease (PD) is still debated. Aim of this study is to assess the autonomic functions in de novo PD patients (dnPD) in comparison with PD patients on therapy (PDot) and healthy controls (HC). MethodsTwenty-eight dnPD and 24 PDot, to whom Unified Parkinson's Rating Scale (UPDRS) was administered, and 23 HC underwent electrochemical skin conductance (ESC) measured with sudoscan, cardiovascular reflexes (head-up tilt test HUTT, Valsalva maneuver, deep breathing, hand grip, and cold face),and Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction (SCOPA-AUT) questionnaire. ResultsThe mean SCOPA-AUT total score was significantly higher in dnPD group compared with HC group (p < 0.001) and significantly lower than PDot (p = 0.004). No significant difference of ESC mean values were found between dnPD and HC group. DnPD had a significantly lower diastolic blood pressure (BP) response at handgrip test (p = 0.005) compared with HC. Hands and feet ESC significantly negatively correlated with disease duration (p = 0.014; p = 0.025) and feet ESC significantly negatively correlated with UPDRS III (p = 0.039). Systolic and diastolic BP responses at 3rd minute of HUTT correlated significantly negatively with disease duration (p < 0.001; p = 0.003) and with UPDRSIII (p = 0.001; p < 0.001). BP response to Valsalva maneuver negatively correlated with UPDRSIII (p = 0.006). ConclusionAlthough dnPD patients complain of thermoregulatory symptoms, we found no alteration in the sudomotor function investigated with sudoscan. Furthermore, a deficit of the sympathetic vasoconstrictive response to the isometric exercise was detected, suggesting an early involvement of the autonomic cardiovascular components in dnPD.

Qualitative and quantitative muscle ultrasound in patients with Duchenne muscular dystrophy: Where do sonographic changes begin?

The number of studies investigating and understanding the disease mechanisms of Duchenne muscular dystrophy (DMD) in human clinical trials have increased substantially over the last decade. Suitable clinical instruments for the measurement of disease progress and drug efficiency are mandatory, but currently not available, especially in the youngest patients. The aim of this study was to detect a reproducible pattern of muscle involvement in early stages potentially preceding evidence of motor regression. A cohort of 25 DMD patients aged 1-6yearsat the first presentation were examined at multiple timepoints and compared with age-matched healthy controls. Muscle ultrasound was quantified using computer-analyzed gray scale levels (GSL) and blinded visual rating, using a modified Heckmatt scale. Changes in muscle echogenicity in DMD patients occurred very early, clearly preceding motor regression and in some cases, even before the motor plateau phase was reached. Visual rating and GSL identified the earliest changes in the proximal adductor magnus muscle. Muscle ultrasound can be used as an additional method to assess the disease progression and for decision-making in paucisymptomatic DMD patients. Sonographic changes in the ad-ductor magnus muscle seem to be the first detectable changes with a recognisable pattern.

Early Detection of Left Ventricular Subclinical Systolic Dysfunction in Hypertensive Patients: Speckle Tracking at Rest and after Dobutamine Stress Echocardiography Study

Abstract Background: Hypertension is one of the major cardiovascular risk factor that may result in heart failure. Two-D transthoracic echocardiography (2-D TTE) recognizes reduction in left ventricular systolic function in late stages of the disease course, so early detection is of paramount importance. Objective: Our study intended to evaluate feasibility of speckle-tracking echocardiography (STE) to provide additional perceptions for early detection of hypertension induced left ventricular systolic dysfunction. Patient and Methods: We enrolled 40 hypertensive patients, 21 women (52.5%) their mean age was 54.55±9 years and 20 normotensive age and gender matched control individuals (10 women, their mean age was 53.20±12.06 years). All had normal left ventricular systolic function by 2-D TTE. STE performed at rest and low dose dobutamine. Patients with significant ischemic or valvular heart disease as well as atrial fibrillation, conduction abnormalities and diabetes excluded. Results: Systolic blood pressure was significantly higher in the hypertensive group patients (138.50±10.27 mmHg vs. 120.50±7.76 mmHg, respectively; P = <0.001). Compared to control group, hypertensive patients experienced significantly impaired global longitudinal STE at rest (-18.08±1.63% versus 20.50±1.52% respectively; P<0.001) and at low-dose dobutamine (-19.11±1.75% versus 22.61±1.88% respectively; P<0.008). Conclusion: Speckle tracking echocardiography increases the sensitivity in detecting subclinical cardiac involvement in early stages of hypertension compared to conventional 2-D echocardiography.

Decay in Retinoic Acid Signaling in Varied Models of Alzheimer's Disease and In-Vitro Test of Novel Retinoic Acid Receptor Ligands (RAR-Ms) to Regulate Protective Genes.

Retinoic acid has been previously proposed in the treatment of Alzheimer’s disease (AD). Here, five transgenic mouse models expressing AD and frontotemporal dementia risk genes (i.e., PLB2APP, PLB2TAU, PLB1Double, PLB1Triple, and PLB4) were used to investigate if consistent alterations exist in multiple elements of the retinoic acid signaling pathway in these models. Many steps of the retinoic acid signaling pathway including binding proteins and metabolic enzymes decline, while the previously reported increase in RBP4 was only consistent at late (6 months) but not early (3 month) ages. The retinoic acid receptors were exceptional in their consistent decline in mRNA and protein with transcript decline of retinoic acid receptors β and γ by 3 months, before significant pathology, suggesting involvement in early stages of disease. Decline in RBP1 transcript may also be an early but not late marker of disease. The decline in the retinoic acid signaling system may therefore be a therapeutic target for AD and frontotemporal dementia. Thus, novel stable retinoic acid receptor modulators (RAR-Ms) activating multiple genomic and non-genomic pathways were probed for therapeutic control of gene expression in rat primary hippocampal and cortical cultures. RAR-Ms promoted the non-amyloidogenic pathway, repressed lipopolysaccharide induced inflammatory genes and induced genes with neurotrophic action. RAR-Ms had diverse effects on gene expression allowing particular RAR-Ms to be selected for maximal therapeutic effect. Overall the results demonstrated the early decline of retinoic acid signaling in AD and frontotemporal dementia models and the activity of stable and potent alternatives to retinoic acid as potential therapeutics.

Comparable Genomic Copy Number Aberrations Differ across Astrocytoma Malignancy Grades.

A collection of intracranial astrocytomas of different malignancy grades was analyzed for copy number aberrations (CNA) in order to identify regions that are driving cancer pathogenesis. Astrocytomas were analyzed by Array Comparative Genomic Hybridization (aCGH) and bioinformatics utilizing a Bioconductor package, Genomic Identification of Significant Targets in Cancer (GISTIC) 2.0.23 and DAVID software. Altogether, 1438 CNA were found of which losses prevailed. On our total sample, significant deletions affected 14 chromosomal regions, out of which deletions at 17p13.2, 9p21.3, 13q12.11, 22q12.3 remained significant even at 0.05 q-value. When divided into malignancy groups, the regions identified as significantly deleted in high grades were: 9p21.3; 17p13.2; 10q24.2; 14q21.3; 1p36.11 and 13q12.11, while amplified were: 3q28; 12q13.3 and 21q22.3. Low grades comprised significant deletions at 3p14.3; 11p15.4; 15q15.1; 16q22.1; 20q11.22 and 22q12.3 indicating their involvement in early stages of tumorigenesis. Significantly enriched pathways were: PI3K-Akt, Cytokine-cytokine receptor, the nucleotide-binding oligomerization domain (NOD)–like receptor, Jak-STAT, retinoic acid-inducible gene (RIG)-I-like receptor and Toll-like receptor pathways. HPV and herpex simplex infection and inflammation pathways were also represented. The present study brings new data to astrocytoma research amplifying the wide spectrum of changes that could help us identify the regions critical for tumorigenesis.

Abnormal Nailfold Capillaroscopy Is Common in Patients with Connective Tissue Disease and Associated with Abnormal Pulmonary Function Tests.

To assess the presence of a systemic sclerosis (SSc) pattern on nailfold capillary microscopy (NCM) in patients with Raynaud phenomenon (RP) and to explore its association with abnormal pulmonary function tests (PFT). NCM patterns were assessed in 759 consecutive patients with RP. Patterns were classified as normal (n = 354), nonspecific (n = 159), or SSc pattern (n = 246). Abnormal PFT was defined as forced vital or diffusion capacity < 70%. Patients were classified as primary RP (n = 245), or secondary: no definite diagnosis (n = 391), SSc (n = 40), primary Sjögren syndrome (pSS; n = 30), systemic lupus erythematosus (SLE; n = 30), mixed connective tissue disease (MCTD; n = 7), rheumatoid arthritis (RA; n = 15). An SSc pattern on NCM was frequently observed in most patients with a definite diagnosis: SSc (88%), pSS (33%), SLE (17%), MCTD (71%), and RA (13%). In patients without definite diagnosis, 17% had a normal NCM pattern, 35% nonspecific, and 48% SSc pattern. Abnormal PFT was more frequent in patients with an SSc pattern (35.9% vs 19.5%, p = 0.002), even when corrected for SSc diagnosis (p = 0.003). Absence of an SSc pattern had high negative predictive value (88%); positive predictive values were low. SSc pattern on NCM is common in patients with RP, and in those with connective tissue diseases other than SSc. It is associated with a higher prevalence of abnormal PFT, independent of the presence of an SSc diagnosis. Although these data need validation in a prospective setting, they underline the importance of NCM in RP and putative value to stratify the risk of pulmonary involvement in early stages of disease.

Signaling pathways activated by PACAP in MCF-7 breast cancer cells

PACAP has opposing roles ranging from activation to inhibition of tumor growth and PACAP agonists/antagonists could be used in tumor therapy. In this study, the effect of PACAP stimulation on signaling pathways was investigated in MCF-7 human adenocarcinoma breast cancer cells. Results showed that MCF-7 cells express VPAC1 and VPAC2, but not PAC1, receptors. In addition, PACAP increased the phosphorylation levels of STAT1, Src and Raf within seconds, confirming their involvement in early stages of PACAP signaling whereas maximal phosphorylation of AKT, ERK and p38 was reached 10 to 20 min later. Moreover, selective inhibition of Src or PI3K resulted in a significant decrease in the phosphorylation of ERK and AKT, but not p38, demonstrating that PACAP signaling follows Src/Raf/ERK and PI3K/AKT pathways. On the other hand, selective inhibition of PLC or PKA resulted in a significant decrease in the phosphorylation of p38, but not AKT or ERK, indicating that PACAP signaling also follows the PLC and PKA/cAMP pathways. Furthermore, PACAP induced ROS through H₂O₂ production whereas pretreatment with NAC inhibitor decreased AKT and ERK phosphorylation, but not p38. Selective NOX2 inhibition affected Src/Raf/Erk and PI3K/Akt pathways, without affecting the p38/PLC/PKA pathway whereas other inhibitors (ML171, VAS2870) had no effect on PACAP induced ROS generation. On the other hand, PACAP induced calcium release, which was decreased by pretreatment with PLC inhibitor. Finally, PACAP stimulation promoted apoptosis by increasing Bax and decreasing Bcl2 expression. In conclusion, we demonstrated that PACAP signaling in MCF-7 cells follows the Src/Raf/ERK and PI3K/AKT pathways and is VPAC1 dependent in a ROS dependent manner, whereas it follows PLC and PKA/cAMP pathways and is VPAC2 dependent through p38 MAP kinase activation involving calcium.

99mTc-HMPAO brain SPECT in the monitoring of cerebral vasculitis therapy

ObjectiveThe central nervous system (CNS) may be involved in a variety of inflammatory diseases of the blood vessels, generally known as vasculitis. The clinical diagnosis of such involvement in early stages is difficult, since a mild cognitive impairment can be the only symptom. It was hypothesized that brain-perfusion SPECT would be able to reveal CNS involvement and to monitor the course of the disease. The purpose of this study was assess if and when an improvement of cerebral perfusion can be registered by SPECT during the follow-up of these diseases. Material and methodsEighteen patients affected by Systemic Lupus Erythematosus (SLE), 22 by undifferentiated vasculitis (UV), 5 by Behcet's disease (BD) and 5 by primary Sjogren's Syndrome (pSS) were enrolled in this prospective study. A 99mTc-HMPAO brain perfusion SPECT was performed before the treatment and was repeated during the follow-up at different time intervals. Image analysis was performed on 10 cerebral areas using a specific software. ResultsIn the SLE patients, no significant improvement of brain perfusion was found. On the contrary, in the UV the cerebral uptake of the tracer significantly improved from the twenty-fourth month (18/22 patients). Patients with BD showed an improvement of scintigraphic findings (5/5 patients), while a similar result was obtained only in 2 of the patients with pSS. ConclusionsIn conclusion, brain SPECT seems to be able to monitor the disease in UV, indicating the moment when an improvement of the cerebral perfusion is achieved. In SLE patients this scintigraphic technique did not show a significant improvement in CNS perfusion.

Towards a Circuit-Level Understanding of Hippocampal CA1 Dysfunction in Alzheimer's Disease Across Anatomical Axes

The hippocampus has been a primary region of study with regards to synaptic and functional changes in Alzheimer’s disease (AD) due to its involvement in early stages, specifically area CA1. However, most work in this area has treated CA1 as a homogeneous structure comprised of uniform neural circuits. Yet, there is a plethora of evidence that CA1 varies in its structure and function across anatomical axes. Here I review the heterogeneity of the functional and circuit architecture of hippocampal area CA1 across three primary anatomical axes. I also summarize evidence that AD differentially affects these subregions, as well as hypotheses as to why this may occur.

New Insights into Cardiac Involvement in Juvenile Scleroderma: A Three-Dimensional Echocardiographic Assessment Unveils Subclinical Ventricle Dysfunction.

Cardiac manifestations in juvenile scleroderma or systemic sclerosis (JSSc) have poor prognosis, begin in early stages of the disease, and remain clinically asymptomatic. New echocardiography modalities, such as 2D/3D speckle tracking (STE, strain analysis for regional and global ventricular functions), can detect cardiac involvement in early stages. We assessed 21 JSSc patients and 19 controls using 2D/3D STE. The left ventricular end diastolic volume, end systolic volume, and ejection fraction of the patient and control groups were significantly different (99.2±23.8 vs. 52±23.8, 40.6±16.0 vs. 20.2±17.4 and 59.2±7.5 vs. 65.6±5.2, respectively). Global longitudinal strain (GLS) and global circumferential strain (GCS) were lower in the patient group (18.4±4.7 vs. 22.4±3.7, 26.4±5.8 vs. 31.4±3.5), as were the peak systolic strain values of the right ventricular longitudinal strain (RVLS) septum and RVLS free wall (18.1±6.8 vs. 24.8±6.0 and 22.8±5.9 vs. 28.0±6.9, respectively). 3D measurements of RVEDV, RVESV, and RVSV were higher in the patient group (88.2±31.3 vs. 50.8±23.5, 43.1±17.6 vs. 19.0±12.2, and 45.0±16.2 vs. 31.7±12.6). RVLS freewall results were lower in the JSSc patients with interstitial lung fibrosis, arthritis, muscle weakness, weight loss, and anti-scl 70 antibodies than in the JSSc patients without these variables. We found that a GCS of <34.5% could identify patients for left ventricular (LV) dysfunction with a sensitivity of 93.3, specificity of 92.9, while an RVEF of <60.7% could identify patients for left ventricular (RV) dysfunction with a sensitivity of 92.9 and specificity of 21.4%. We highlighted key advantages of 3D STE for the tracking of early systolic dysfunction in patients with JSSc who would benefit from medical intervention for cardiac complications.

Pleural irregularities and mediastinal pleural involvement in early stages of malignant pleural mesothelioma and benign asbestos pleural effusion

ObjectiveTo elucidate differences in the level and localization of pleural irregularities in early malignant pleural mesothelioma (eMPM) and benign asbestos pleural effusion (BAPE) using CT. Study designRetrospective assessment of CT findings of consecutive patients with BAPE at a single centre and patients with eMPM reported in Japanese vital statistics. MethodologyThirty-six patients with confirmed diagnoses of BAPE and sixty-six patients with confirmed diagnoses of eMPM (mesothelioma stages T1 or T2) were included. Informed consent, CT scans, and clinical and pathologic details were obtained for all patients and were reviewed by one radiologist, two pathologists, and two pulmonologists. Asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening were assessed in all patients. ResultsPrevalence of asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening was significantly higher in the BAPE group. Low-level irregularity was more common in the BAPE group (p<0.001), whereas high-level irregularity, mediastinal localization, and interlobar fissure were more prevalent in the eMPM group (p<0.001). Interlobar pleural irregularity was not observed in any patients in the BAPE group, although 55% of patients in the eMPM group showed interlobar pleural irregularity. Mediastinal pleural involvement was observed in 74% of patients in the eMPM group and had a positive predictive value of 89%. ConclusionThis study demonstrates that the level and localization of plural irregularities significantly differed between patients with BAPE and eMPM. Large-scale prospective studies are needed to fully establish the diagnostic utility of such differences.

Identification of β-Dystrobrevin as a Direct Target of miR-143: Involvement in Early Stages of Neural Differentiation.

Duchenne Muscular Dystrophy, a genetic disorder that results in a gradual breakdown of muscle, is associated to mild to severe cognitive impairment in about one-third of dystrophic patients. The brain dysfunction is independent of the muscular pathology, occurs early, and is most likely due to defects in the assembly of the Dystrophin-associated Protein Complex (DPC) during embryogenesis. We have recently described the interaction of the DPC component β-dystrobrevin with members of complexes that regulate chromatin dynamics, and suggested that β-dystrobrevin may play a role in the initiation of neuronal differentiation. Since oxygen concentrations and miRNAs appear as well to be involved in the cellular processes related to neuronal development, we have studied how these factors act on β-dystrobrevin and investigated the possibility of their functional interplay using the NTera-2 cell line, a well-established model for studying neurogenesis. We followed the pattern of expression and regulation of β-dystrobrevin during the early stages of neuronal differentiation induced by exposure to retinoic acid (RA) under hypoxia as compared with normoxia, and found that β-dystrobrevin expression is regulated during RA-induced differentiation of NTera-2 cells. We also found that β-dystrobrevin pattern is delayed under hypoxic conditions, together with a delay in the differentiation and an increase in the proliferation rate of cells. We identified miRNA-143 as a direct regulator of β-dystrobrevin expression, demonstrated that β-dystrobrevin is expressed in the nucleus and showed that, in line with our previous in vitro results, β-dystrobrevin is a repressor of synapsin I in live cells. Altogether the newly identified regulatory pathway miR-143/β-dystrobrevin/synapsin I provides novel insights into the functions of β-dystrobrevin and opens up new perspectives for elucidating the molecular mechanisms underlying the neuronal involvement in muscular dystrophy.

Pulmonary involvement in rheumatoid arthritis: A cross-sectional study in Iran.

Background:Interstitial lung disease (ILD) is a type of pulmonary manifestation in patients with rheumatoid arthritis (RA). Mostly RA-ILD has no symptoms and is only diagnosed by clinical examination, pulmonary function test (PFT), and high-resolution computed tomography (HRCT); hence it seems that the diagnosis of pulmonary involvement in early stages of RA is of great importance. Therefore, we decided to answer this question whether the evaluation of RA patients without pulmonary symptoms using methods such as PFT and HRCT are justifiable and reasonable or not.Methods:We conducted a cross-sectional study in a referral rheumatology clinic in Razi hospital of Rasht, Iran. Forty-four consecutive patients, diagnosed with RA, were enrolled. Physical examination of the joints was performed by an rheumatologist. The activity of RA was evaluated in all patients by Disease Activity Score 28. An expert pulmonologist performed the respiratory examination in all participants. Then, all subjects were referred for chest X-ray, PFT, and HRCT of lungs.Results:Patients included in this study, 9 (20.45%) males and 35 (79.55%) females, were 21–73 years old and their mean age was 49 ± 13 years. Significant relation between PFT and respiratory complaints was observed (P = 0.016). PFT had significant relation with respiratory examinations (P = 0.009). Our results indicated a significant relation between disease activity rate and PFT (P = 0.038). While HRCT had any significant relation with above items.Conclusion:We concluded, using PFT in the respiratory assessment of RA patients can be limited to persons with high disease activity, respiratory complaints, and positive findings in the clinical respiratory examination.