Early Morphological Changes Research Articles

Repeatability of CBCT radiomic features and their correlation with CT radiomic features for prostate cancer.

Radiomic features of cone-beam CT (CBCT) images have potential as biomarkers to predict treatment response and prognosis for patients of prostate cancer. Previous studies of radiomic feature analysis for prostate cancer were assessed in a variety of imaging modalities, including MRI, PET, and CT, but usually limited to a pretreatment setting. However, CBCT images may provide an opportunity to capture early morphological changes to the tumor during treatment that could lead to timely treatment adaptation. This work investigated the quality of CBCT-based radiomic features and their relationship with reconstruction methods applied to the CBCT projections and the preprocessing methods used in feature extraction. Moreover, CBCT features were correlated with planning CT (pCT) features to further assess the viability of CBCT radiomic features. The quality of 42 CBCT-based radiomic features was assessed according to their repeatability and reproducibility. Repeatability was quantified by correlating radiomic features between 20 CBCT scans that also had repeated scans within 15minutes. Reproducibility was quantified by correlating radiomic features between the planning CT (pCT) and the first fraction CBCT for 20 patients. Concordance correlation coefficients (CCC) of radiomic features were used to estimate the repeatability and reproducibility of radiomic features. The same patient dataset was assessed using different reconstruction methods applied to the CBCT projections. CBCT images were generated using 18 reconstruction methods using iterative (iCBCT) and standard (sCBCT) reconstructions, three convolution filters, and five noise suppression filters. Eighteen preprocessing settings were also considered. Overall, CBCT radiomic features were more repeatable than reproducible. Five radiomic features are repeatable in>97% of the reconstruction and preprocessing methods, and come from the gray-level size zone matrix (GLSZM), neighborhood gray-tone difference matrix (NGTDM), and gray-level-run length matrix (GLRLM) radiomic feature classes. These radiomic features were reproducible in>9.8% of the reconstruction and preprocessing methods. Noise suppression and convolution filter smoothing increased radiomic features repeatability, but decreased reproducibility. The top-repeatable iCBCT method (iCBCT-Sharp-VeryHigh) is more repeatable than the top-repeatable sCBCT method (sCBCT-Smooth) in 64% of the radiomic features. Methods for reconstruction and preprocessing that improve CBCT radiomic feature repeatability often decrease reproducibility. The best approach may be to use methods that strike a balance repeatability and reproducibility such as iCBCT-Sharp-VeryLow-1-Lloyd-256 that has 17 repeatable and eight reproducible radiomic features. Previous radiomic studies that only used pCT radiomic features have generated prognostic models of prostate cancer outcome. Since our study indicates that CBCT radiomic features correlated well with a subset of pCT radiomic features, one may expect CBCT radiomics to also generate prognostic models for prostate cancer.

Near-fiber electromyography

ObjectiveDescribe and evaluate the concepts of near fiber electromyography (NFEMG), the features used, including near fiber motor unit potential (NFMUP) duration and dispersion, which relate to motor unit distal axonal branch and muscle fiber conduction time dispersion, and NFMUP segment jitter, a new measure of the temporal variability of neuromuscular junction transmission (NMJ), and axonal branch and muscle fibre conduction for the near fibres (i.e. NF jitter), and the methods for obtaining their values. MethodsTrains of high-pass filtered motor unit potentials (MUPs) (i.e. NFMUP trains) were extracted from needle-detected EMG signals to assess changes in motor unit (MU) morphology and electrophysiology caused by neuromuscular disorders or ageing. Evaluations using simulated needle-detected EMG data were completed and example human data are presented. ResultsNFEMG feature values can be used to detect axonal sprouting, conduction slowing and NMJ transmission delay as well as changes in MU fiber diameter variability, and NF jitter. These changes can be detected prior to alterations of MU size or numbers. ConclusionsThe evaluations clearly demonstrate and the example data support that NFMUP duration and dispersion reflect MU distal axonal branching, conduction slowing and NMJ transmission delay and/or MU fiber diameter variability and that NFMUP jiggle and segment jitter reflect NF jitter. SignificanceNFEMG can detect early changes in MU morphology and/or electrophysiology and has the potential to augment clinical diagnosis and tracking of neuromuscular disorders.

Evidence for diagnosis of early chronic pancreatitis after three episodes of acute pancreatitis: a cross-sectional multicentre international study with experimental animal model

Chronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n = 983), recurrent AP (RAP, n = 270) and CP (n = 62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5 + was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3 + do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare.

Mitochondrial Membrane Potential Drives Early Change in Mitochondrial Morphology After Acetaminophen Exposure.

Mitochondrial morphology plays a critical role in regulating mitochondrial and cellular function. It is well established that oxidative stress and mitochondrial injury are central to acetaminophen (APAP) hepatotoxicity. However, the role of mitochondrial dynamics, namely the remodeling of mitochondrial morphology through fusion and fission, has largely gone unexplored. To investigate this, we used primary mouse hepatocytes treated with APAP which allowed for real-time visualization of mitochondrial morphology using mitotracker green. We found that alterations in mitochondrial morphology were dose dependent, with a biphasic response in mitochondrial shape at higher APAP doses. Importantly, these two distinct mitochondrial morphologies corresponded with differences in mitochondrial respiratory function and polarization. The early change in mitochondrial morphology can be reversible and appears to be an adaptive response caused by alterations in membrane potential, which ultimately help preserve mitochondrial function. The later delayed change in mitochondrial morphology is irreversible and is driven by loss of mitochondrial membrane potential, decreased canonical fusion proteins, and alterations in mitochondrial lipid composition. Collectively, these later changes tilt the scales toward mitochondrial fission resulting in fragmented mitochondria with reduced functionality. This work provides evidence of adaptive early changes in mitochondrial morphology, which results in functional consequences that are dictated by the severity of APAP overdose.

Early-life stress induces the development of Alzheimer's disease pathology via angiopathy

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is a major societal, scientific, and economic problem. Several early-life factors associated with an increased risk for the clinical diagnosis of AD have recently been identified. In the present study, we investigated the involvement of early-life stress in the pathogenesis of AD using heterozygous amyloid precursor protein (APP) mutant mice (AppNL-G-F/wt) and wild-type (Appwt/wt) mice. We found that maternal-separated Appwt/wt mice showed narrowing of vessels and decreased pericyte coverage of capillaries in the prefrontal cortex, while maternal-separated AppNL-G-F/wt mice additionally showed the impairment of cognitive function, earlier formation of Aβ plaques, increased vessel-associated microglia, and disruption of the blood–brain barrier. Substantial activation of microglia was detected in the maternal-separated AppNL-G-F/wt mice and maternal-separated Appwt/wt mice. At an early stage, morphological changes and inflammatory responses were observed in the microglia of the maternal-separated AppNL-G-F/wt mice and maternal-separated Appwt/wt mice, and morphological changes in the microglia were observed in the non-maternal-separated AppNL-G-F/wt mice. Microglia activation induced by maternal separation in combination with the APP mutation may impair the vascular system, leading to AD progression. These findings therefore suggest that maternal separation results in the early induction of AD-related pathology via angiopathy.

Alzheimer’s disease–related atrophy patterns in different definitons of subjective cognitive decline

AbstractBackgroundDifferent criteria sets were suggested for better operationalization of subjective cognitive decline. In this study, we aimed to assess structural neuroimaging biomarkers of AD in different definitions of SCD.MethodThe study was conducted at Hacettepe University, Turkey. 101 participants over 55 years of age, with memory complaints and no identifiable impairment in a valid cognitive screening test (Z scores>‐1.5 in the Modified Mini Mental Test 3MS) were included. We evaluated whether (i) using a scale (Subjective Memory Complaints Questionnaire‐SMCQ) rather than a single question assessing the subjective complaint; (ii) utilizing neuropsychological test data in addition to a screening test; (iii) evaluating SCD + criteria (additional qualitative features of the complaint) and (iv) the exclusion of comorbidities that may be associated with memory complaints; would be associated with increased atrophy in AD‐related areas. Three different cortical thickness and two cortical volume patterns based on previous research were determined as the dependent variables. MR images were obtained with a 1.5 Tesla MRI scanner. Cortical thickness and gray matter volumes were estimated using the FreeSurfer Software package version 6.0 on 3D T1‐weighted MRI scans (MP RAGE), in accordance with ADNI‐1 MRI acquisition protocol. The multivariate regression models were performed for evaluating the relationship of each independent variable.ResultResults suggested that age, sex, age of onset of memory complaints, depression or anxiety symptoms and vitamin B12 and vitamin D levels were associated with alterations in the structural markers of AD. Regarding different definitions of SCD; assessment of SCD + criteria, utilizing SMCQ, addition of neuropsychological test data and excluding individuals with comorbidities did not contribute to the validity of SCD in terms of the AD morphology.ConclusionOur findings indicate the importance of psychiatric evaluation in individuals with subjective memory complaints. The presence of depression and anxiety symptoms in a person with SCD may increase the likelihood of AD‐related brain morphological changes. Longitudinal studies, better assessment of the phenotype, inclusion of different diagnostic groups may help to refine the definition of SCD and the addition of criterion which may point to early morphological changes. This study has been funded by TUBITAK 214S048, Hacettepe THD‐2018‐17363.

Morpho-functional effects of different universal dental adhesives on human gingival fibroblasts: an in vitro study

To analyze the effects of four universal adhesives (Optibond Solo Plus—OB, Universal Bond—UB, Prime&Bond Active—PBA, FuturaBond M + —FB) on human gingival fibroblasts in terms of cytotoxicity, morphology and function. After in vitro exposure for up to 48 h, fibroblast viability was determined by the MTT assay determined, morphology by phase-contrast microscopy and migration by the scratch wound assay. Expression levels of IL1β, IL6, IL8, IL10, TNFα and VEGF genes were assessed by RT-PCR and their protein production by Western blot analysis. Apoptosis and cell cycle were analyzed by flow cytometry. OB and UB induced early morphological changes on fibroblasts (3 h) with extended cell death at 24 h/48 h. Gene expression of collagen type I and fibronectin increased fivefold compared with controls, elastin disappeared and elastase increased threefold, indicating gingival tissue tended to become fibrotic. Only UB and OB increased gene expression of inflammatory markers: IL1β at 3 and 48 h (up to about three times), IL6 and IL8 at 3 h (up to almost four times) which corresponded to the increase of the activated form NF-kB. All adhesives showed an effect on the functionality of fibroblasts with cytotoxic effect time and concentration dependent. Among all the OB and UB adhesives, they showed the greatest cell damage. The in-depth analysis of the effects of universal adhesives and possible functional effects represents an important information for the clinician towards choosing the most suitable adhesive system.

Application of atomic force microscopy to assess erythrocytes morphology in early stages of diabetes. A pilot study

The study aim was to assess the application of atomic force microscopy (AFM) to evaluate erythrocyte morphology in early stages of type 2 diabetes mellitus, and the association with biochemical, anthropometric, diet, and physical activity indicators.This was a pilot cross-sectional study with four groups: healthy individuals, people with prediabetes (PDG), metabolic syndrome (MSG), and diabetes mellitus group (DMG). Blood samples were obtained to assess the erythrocyte morphology and biochemical parameters. Anthropometrical measurements were taken. Besides, a diet and a physical activity questionnaire were applied.The evaluation of the erythrocyte morphology through the AFM showed quantitative and qualitative alterations in the cell's form and size. Compared to the healthy group, the PDG had a reduction in height (-0.80 μm, p < 0.05), and an increase in axial ratio (-0.09 μm, p < 0.05); the MSG had lower concave depth (-0.19 μm, p < 0.05); and the DMG had a decreased height (-0.46 μm, p < 0.05) and concave depth (-0.29 μm, p < 0.05), and higher axial ratio (+0.08 μm) and thickness (+0.32 μm, p < 0.05). The PDG vs. DMG had a statistically significant difference in concave depth (+0.23 μm, p < 0.05) and thickness (-0.26 μm, p < 0.05). The MSG was different than the DMG in variables like axial ratio (-0.05 μm) and thickness (-0.25 μm). Besides, higher values of age, HbA1c, triglycerides, body mass index, waist-to-hip ratio, and physical inactivity were associated with altered erythrocyte morphology.AFM is a promising instrument to assess early but subtle changes in erythrocyte morphology (height, axial ratio, concave depth, thickness) before significant pathological conditions, such as type 2 diabetes mellitus. HbA1c might have a major effect in altered morphology, vs. metabolic parameters like high triglycerides, body mass index, waist, and physical inactivity.

Correlation between the degree of pancreatic fibrosis and secretin stimulated pancreatic secretion in patients with early morphological changes of chronic pancreatitis

Correlation between the degree of pancreatic fibrosis and secretin stimulated pancreatic secretion in patients with early morphological changes of chronic pancreatitis

Early physiological and morphological changes in the remnant kidney of living donors.

In order to describe the early functional and morphological changes in the remnant kidney of living donors, a retrospective study was carried out at the Cayetano Heredia Hospital. Data from 55 individuals was included. Clinical and demographic data were obtained from the clinical records, as well as data for creatinine clearance, proteinuria, blood pressure and renal dimensions at 1, 2, 3, 6 and 12 months after kidney donation. The mean age was 40.88 (±9.84) years; 80% were women and the mean body mass index was 25.68 (±3.5) kg/m2. Linear and quadratic models were used to study physiological and morphological variables. During the follow-up time, glomerular filtration rate, proteinuria, diastolic blood pressure, and kidney length showed significant changes (p < 0.05).

Foetal haemodynamic response to anaemia.

This study aims to update new knowledge regarding foetal cardiovascular response to anaemia, using foetal haemoglobin Bart's disease as a study model. Original research articles, review articles, and guidelines were narratively reviewed and comprehensively validated. The main foetal cardiovascular changes in response to anaemia are consequences of hypervolaemia and increased cardiac output to meet tissue oxygen requirement. New challenging insights are as follows: (i) the earliest morphological change is an increase in cardiac size and remodelling of the sphericity (an increase in diameter more pronounced than that in long axis) followed by several markers, such as placentomegaly and hepatosplenomegaly. (ii) The earliest functional change is increased peak systolic velocity of the red blood cells because of low viscosity, especially in the middle cerebral artery. (iii) The foetal heart has very high reserve potentials to cope with anaemia: increasing workload without increased central venous pressure and increased myocardial performance without compromising shortening fraction. This hard‐working period with good performance lasts long, including most part of the second and third trimester. (iv) At the time cardiomegaly myocardial cellular damage has already occurred, in spite of good cardiac function. (v) Anaemic hydrops foetalis is mainly due to hypervolaemia, hypoalbuminaemia, and high vascular permeability, not heart failure. (vi) Foetal heart failure occurs only when the adaptive mechanism becomes exhausted or long after the development of anaemic hydrops foetalis. Heart failure is a very late result of a longstanding overworked heart. (vii) Ultrasound is highly effective in the detection of foetal response to anaemia. An increase in cardiac size and middle cerebral artery is very helpful in predicting the affected foetuses in pre‐hydropic phase. (viii) Theoretically, intrauterine treatment of anaemic hydrops results in satisfactory outcomes as long as cardiac function is normal, but intrauterine intervention should be strongly considered in pre‐hydropic phase because myocardial cell damage could have already occurred in this phase or early hydropic phase. Anaemic hydrops foetalis is not primarily caused by heart failure as commonly advocated, but it is rather a consequence of hypervolaemia, hypoalbuminaemia, and high vascular permeability while heart failure is a very late consequence of a longstanding overworked heart. New insights gained from this review may be useful to base clinical practice on which sonographic markers imply significant pathological changes, how ultrasound can be helpful in early detection of anaemic response, when intrauterine transfusion for anaemia due to non‐lethal causes should be administered, etc.

The effect of amyloid on microglia-neuron interactions before plaque onset occurs independently of TREM2 in a mouse model of Alzheimer's disease

Genetic studies identified mutations in several immune-related genes that confer increased risk for developing Alzheimer's disease (AD), suggesting a key role for microglia in AD pathology. Microglia are recruited to and actively modulate the local toxicity of amyloid plaques in models of AD through these cells' transcriptional and functional reprogramming to a disease-associated phenotype. However, it remains unknown whether microglia actively respond to amyloid accumulation before plaque deposition in AD. We compared microglial interactions with neurons that exhibit amyloid accumulation to those that do not in 1-month-old 5XFAD mice to determine which aspects of microglial morphology and function are altered by early 6E10+ amyloid accumulation. We provide evidence of preferential microglial process engagement of amyloid laden neurons. Microglia, on exposure to amyloid, also increase their internalization of neurites even before plaque onset. Unexpectedly, we found that triggering receptor expressed on myeloid cells 2 (TREM2), which is critical for microglial responses to amyloid plaque pathology later in disease, is not required for enhanced microglial interactions with neurons or neurite internalization early in disease. However, TREM2 was still required for early morphological changes exhibited by microglia. These data demonstrate that microglia sense and respond to amyloid accumulation before plaques form using a distinct mechanism from the TREM2-dependent pathway required later in disease.

Morphogenesis of the lens placode.

For over 100 years, the vertebrate eye has been an important model system to understand cell induction, cell shape change, and morphogenesis during development. In the past, most of the studies examined histological changes to detect the presence of induction mechanisms, but the advancement of molecular biology techniques has made exploring the genetic mechanisms behind lens development possible. Despite the particular emphasis given to the induction of the lens placode, there are still many aspects of the cell biology of lens morphogenesis to be explored. Here, we will revisit the classical detailed description of early lens morphological changes, correlating it with the cell biology mechanisms and with the molecules and signaling pathways identified up to now in chick and mouse embryos. A detailed description of lens development stages helps better understand the timeline of the events involved in early lens morphogenesis. We then point to some key questions that are still open.

A Probe into the Parallel Elements of Diabetes Mellitus and Alzheimer’s Disease

Alzheimer’s Disease (AD) is a standout amongst the most familiar types of memory loss influencing a huge number of senior individuals around the world which is the main source of dementia and memory misfortune. AD causes shrinkage in hippocampus and cerebral cortex and it grows the ventricles in the mind Enhancing home and network based composed consideration is basic to alleviating Alzheimer’s impacts on people and families and to decreasing mounting medicinal services costs. Distinguishing early morphological changes in the mind and making early determination are vital for Alzheimer’s ailment (AD). A few machine learning techniques, for example, Support vector machines have been utilized and a portion of these strategies have been appeared to be extremely compelling in diagnosing AD from neuroimages, some of the time significantly more viable than human radiologists. MRI uncover the data of AD however decay districts are diverse for various individuals which makes the finding somewhat trickier. By utilizing Convolutional Neural Networks, the issue can be settled with insignificant mistake rate. This paper proposes a profound Convolutional Neural Network (CNN) for Alzheimer’s Disease finding utilizing mind MRI information examination. The calculation was prepared and tried utilizing the MRI information from Alzheimer’s Disease Neuroimaging Initiative.

Astrocyte regional diversity in ALS includes distinct aberrant phenotypes with common and causal pathological processes

Astrocytes are major contributors of motor neuron (MN) degeneration in amyotrophic lateral sclerosis (ALS). We investigated whether regional and cell maturation differences influence ALS astrocyte malfunction. Spinal and cortical astrocytes from SOD1G93A (mSOD1) 7-day-old mice were cultured for 5 and 13 days in vitro (DIV). Astrocyte aberrancies predominated in 13DIV cells with region specificity. 13DIV cortical mSOD1 astrocytes showed early morphological changes and a predominant reactive and inflammatory phenotype, while repressed proteins and genes were found in spinal cells. Inflammatory-associated miRNAs, e.g. miR-155/miR-21/miR-146a, were downregulated in the first and upregulated in the later ones. Interestingly, depleted miR-155/miR-21/miR-146a in small extracellular vesicles (sEVs/exosomes) was a common pathological feature. Cortical mSOD1 astrocytes induced late apoptosis and kinesin-1 downregulation in mSOD1 NSC-34 MNs, whereas spinal cells upregulated dynein, while decreased nNOS and synaptic-related genes. Both regional-distinct mSOD1 astrocytes enhanced iNOS gene expression in mSOD1 MNs. We provide information on the potential contribution of astrocytes to ALS bulbar-vs. spinal-onset pathology, local influence on neuronal dysfunction and their shared miRNA-depleted exosome trafficking. These causal and common features may have potential therapeutic implications in ALS. Future studies should clarify if astrocyte-derived sEVs are active players in ALS-related neuroinflammation and glial activation.

New response evaluation criteria using early morphological change in imatinib treatment for patients with gastrointestinal stromal tumor.

838 Background: While the introduction of molecularly targeted drugs, including imatinib, has greatly improved the prognosis of gastrointestinal tumor (GIST), the response evaluation criteria have not been optimized. Early morphological change (EMC) was previously reported as a predictive marker for molecularly targeted drugs in metastatic colorectal cancer. The purpose of the present study was to verify the efficacy of EMC in predicting the outcome in patients with GIST receiving imatinib. Methods: We retrospectively reviewed 55 patients. EMC in computed tomography (CT) image was evaluated, and the patients were categorized into two groups; active MR (morphologic response) (+) group and active MR (-) group, judging from the morphological features including the sharpness of the outline and the attenuation of target lesion. We investigated the association between the presence of active MR and clinical outcomes. Similarly, clinical outcomes classified by response evaluated by RECIST and Choi criteria were analyzed respectively. Results: Thirty-two patients had active MR (+). The median Progression-free survival(PFS) was 7 months vs 31 months (active MR(-) vs active MR(+), P = 0.013) and the median overall survival (OS) was 58 months vs 91 months ( P = 0.086), respectively. Although PFS of RECIST PD (progression disease) or Choi PD patients was shorter than that for PR (partial response) or SD(stable disease) patients ( P = 0.0037 for RECIST, P = 0.0058 for Choi), the number of PD patients was very small (N = 3, both in RECIST and Choi). Conclusions: The evaluation criteria based on EMC could be a sensitive method to predict the clinical outcome of imatinib treatment for patients with inoperative GIST.

P1507 Early and late morphological changes in the athlete"s heart: a longitudinal cohort study in young elite athletes

Abstract Funding Acknowledgements South-Eastern Norway Regional Health Authority OnBehalf Center for Cardiological Innovation Background Recent studies have suggested an initial concentric remodelling in the early development of the athlete’s heart in endurance athletes. However, the development from the early to the fully developed endurance athlete’s heart has not been described in longitudinal studies. Aims This study aims to explore the morphological changes occurring in hearts of young endurance athletes transitioning through adolescence. Methods Forty-eight cross-country skiers were examined at age 12 (12.1 ± 0.2 years) and then again at age 15 (15.3 ± 0.3 years). Cardiopulmonary exercise test and echocardiography, including 3D acquisitions, was performed in all subjects at both baseline and follow-up. Results At follow-up, 31 (65%) of the endurance athletes were still active and 17 (35%) were not. No differences in cardiac morphology were identified at baseline. At 15 years of age, the active endurance athletes had greater VO2 max, 3D indexed left ventricular end-diastolic and end-systolic volumes (Table). Relative wall thickness (RWT) decreased in the active endurance athletes during follow-up (0.35 ± 0.05 to 0.31 ± 0.04, p &amp;lt; 0.001), but not in the former athletes. Four active endurance athletes had RWT above the upper reference values at baseline; at follow up, all had normalized. Conclusion After an early concentric remodeling in the 12 years old athletes, those who continued regular endurance training developed eccentric changes with chamber dilatation and a drop in RWT. In contrast, those who ceased endurance training maintained a comparable wall thickness, but did not develop chamber dilatation nor experience a drop in RWT. Baseline Follow-up Active athletes (n = 31) Former athletes (n = 17) p-value Active athletes (n = 31) Former athletes (n = 17) p-value VO2 max, indexed 65 ± 7 63 ± 7 0.33 62 ± 8 57 ± 6 &amp;lt;0.05 Interventricular septum thickness, mm 7.9 ± 0.8 7.8 ± 1.0 0.54 8.1 ± 1.2 7.8 ± 0.9 0.41 LV end-diastolic diameter, mm/m2 2.1 ± 0.3 2.0 ± 0.3 0.60 3.0 ± 0.2 2.9 ± 0.2 0.34 LV poster wall thickness, mm 7.3 ± 0.9 6.8 ± 0.9 0.07 7.8 ± 1.2 8.1 ± 1.2 0.42 3D LV end-diastolic volume, mL/m2 76 ± 8 74 ± 8 0.89 84 ± 11 79 ± 10 &amp;lt;0.05 3D LV end-systolic volume, mL/m2 33 ± 4 33 ± 4 0.99 36 ± 6 32 ± 3 &amp;lt;0.05 3D LV ejection fraction, % 56 ± 3 56 ± 3 0.93 58 ± 3 59 ± 2 0.52 3D LV Mass/BSA, g/m2 69 ± 7 71 ± 4 0.57 76 ± 11 74 ± 6 0.19 Relative wall thickness 0.35 ± 0.05 0.33 ± 0.05 0.12 0.31 ± 0.04 0.33 ± 0.05 0.05 Data expressed as mean ± SD. P-values calculated using the Student"s paired t-test. Volumes are indexed to body surface area.

Baseline Predictive Factors of Visual Outcome and Persistence of Subretinal Fluid Based on Morphologic Changes in Spectral Domain Optical Coherence Tomography in Patients with Idiopathic Central Serous Chorioretinopathy.

BackgroundTo determine the influence of spectral domain optical coherence tomography (OCT) changes on visual outcome and persistence of subretinal fluid (SRF) in patients with idiopathic central serous chorioretinopathy (CSCR).Materials and methodsIn a retrospective study done in 48 eyes of 45 patients diagnosed as CSCR, all eyes were subjected to fundus photography, spectral domain OCT, and fluorescein angiography (FA) in selected cases.ResultsRetinal pigment epithelium detachment was present in 22.91% of the cases at presentation. The logMar best corrected visual acuity improved from 0.46±0.29 at presentation to 0.18±0.22 at 3 months (P-value<0.01). The mean foveal thickness was 486.81±146.06 µm at presentation and 259±94.5 µm at 3 months (P-value<0.01) (paired T-test). OCT factors that were associated with poor visual outcome (BCVA>0.3 logMar) were disruption in the inner segment (IS)/outer segment (OS) junction or external limiting membrane (ELM) line and hyper-reflective dots in the intra/subretinal layer (P-value<0.05) (Fischer’s Exact test). Out of the total 48 eyes, 26 had persistent SRF at 3 months. The presence of discontinuation in IS/OS junction and hyper-reflective dots in the intra/subretinal layer were the only two OCT factors that were associated with the persistence of SRF (P-value<0.01) (Pearson’s Chi-square test).ConclusionVisual outcome and persistence of subretinal fluid at 3 months can be predicted on the basis of early morphologic changes in OCT. This will aid in counseling patients regarding its course and may guide us in its management.

Idiopathic scoliosis: A pilot MR study of early vertebral morphological changes and spinal asymmetry

Adolescent idiopathic scoliosis (AIS) a common spinal condition affecting adolescents. Though the etiology is still unknown, it is widely thought to have a multifactorial etiology and early diagnosis remains a significant challenge. The purpose of this study is to identify early vertebral morphological changes and patterns of spinal asymmetry in these at-risk individuals who later progress to adolescent idiopathic scoliosis. This was a retrospective study of patients treated for AIS between 1997 and 2017. We utilized two study groups, a group with immature onset of spinal asymmetry and a control group. Inclusion criteria for the immature onset group was defined by a Cobb angle between 10 and 40° diagnosed prior to the age of 12 with MRI scans and XRs available for review. Qualitative assessments observed for sagittal vertebral wedging, analysis of vertebral corner anatomy, spinal harmony, and sagittal balance. These findings were then qualitatively compared between groups. Twenty patients were included in this study, ten each in the immature onset and control groups. In the immature onset group, two patients had sagittal wedging, five had abnormal vertebral corners, nine did not have spinal harmony, and nine had negative sagittal balance, compared to none of the control patients having sagittal wedging, none having abnormal vertebral corners, all having spinal harmony, and nine having positive spinal balance. This pilot MRI study identifies qualitative vertebral morphological changes in patients who progress to AIS. Our findings suggest abnormal vertebral corner anatomy, sagittal wedging, and negative sagittal balance as potential early findings in patients who develop AIS.

Early morphological changes in cardiac mitochondria after subcutaneous administration of trastuzumab in rabbits: possible prevention with oral selenium supplementation.

Trastuzumab-mediated cardiotoxicity poses a significant challenge in the treatment of human epidermal growth factor receptor 2-positive breast cancer. To understand the underlying mechanisms, we conducted experiments to determine ultrastructural changes of rabbit cardiac tissue under different experimental conditions, including differing doses of trastuzumab and supplementation with oral sodium selenite, an antioxidant. Histopathology revealed lymphocyte and macrophage infiltration in myocardium of rabbits receiving four doses of trastuzumab. Transmission electron microscopy showed substantial changes with trastuzumab, including edema with separation of myofibril bundles and rupture of sarcomeres. Within mitochondria, edema resulted in disorganization of the cristae. Some mitochondria exhibited eccentric projections of their membranes with disruption of both inner and outer membranes. These changes were seen to a lesser extent in rabbits who received oral sodium selenite prior to trastuzumab. Selenium is integral to functioning of mitochondrial glutathione peroxidases, important antioxidants that also maintain membrane integrity. If mitochondria are disrupted as part of trastuzumab cardiac toxicity, selenium supplementation might be an important therapeutic or preventive consideration. Larger studies to explore this hypothesis are warranted.