scholarly journals Analysis of cardiomyocyte nuclei in human cardiomyopathy reveals orientation dependent defects in shape

Author(s):  
Daniel Brayson ◽  
Elisabeth Ehler ◽  
Cristobal G dos Remedios ◽  
Catherine M Shanahan

Cardiomyopathies are progressive diseases of heart muscle often caused by mutations in genes encoding sarcomeric, cytoskeletal and nucleoskeletal proteins though in many cases the cause of disease is not identified. Whilst nucleus hypertrophy has been described, it is not known whether nucleus shape changes are a general feature of cardiomyopathy. Due to the rod-shaped nature of cardiomyocytes and their elliptical nuclei we hypothesised that orientation of analysis would be an important determinant of any changes observed between patients exhibiting primarily unexplained cardiomyopathy and control samples from non-failing donors. To investigate this we performed image analysis of cardiomyocyte nuclei in myocardial cryosections from a cohort of cardiomyopathy patients. We discovered that circularity, solidity and aspect ratio were sensitive to orientation of the myocardium and that in the transverse plane only circularity was reduced in cardiomyocyte nuclei of cardiomyopathy patients. These findings show that orientation dependent changes in nucleus shape may be a property of cardiomyopathy and with appropriate follow up studies, may prove to have mechanistic and diagnostic value.

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Maren Bettina Pfenning ◽  
Jessica Schmitz ◽  
Kevin Schulte ◽  
Carsten Hafer ◽  
Abedalrazag Ahmad Khalifa ◽  
...  

Abstract Background and Aims Macrophages and monocytes are main players in innate immunity. In renal diseases, their role is poorly understood. Our multicentric cross-sectional study aimed to study the prevalence of macrophages and monocytes in various human native kidney diseases. For this, we used precise pixel-based digital quantification of their densities in renal biopsies and correlated our findings with clinical data. Method We included 324 patients, who underwent a diagnostic renal biopsy. Additional normal kidney samples from 16 tumour nephrectomies were used as controls. According to the diagnosed diseases, we established 17 patient groups. Biopsies were stained for CD68+-macrophages using automated immunohistochemistry (Ventana Ultra) and selected groups were further subtyped for CD14+-monocytes and CD163+-M2-macrophages (67 cases, pauci-immune glomerulonephritis (PIGN), IgA-nephropathy (IgAN) and control samples). Digitized sections (Leica) were analysed using the open-source software QuPath to quantify cell densities (positively stained areas displayed as percentages of ROI) in renal cortex, medulla and extrarenal tissue, respectively. Detailed clinical and laboratory data at timepoint of biopsy were available for all patients. Additional data for follow-up were achievable in 158 cases. Results Renal disease samples presented higher mean macrophage densities compared to control cases (CD68: cortex 1.2 vs. 0.2%, p<0.001, medulla 0.8 vs. 0.04%, p<0.001; CD163: cortex 3.2 vs. 0.5%, p<0.001, medulla 2.3 vs. 0.6%, p<0.05), but CD14+-density did not differ between patients and control samples. The highest cortical CD68+-density occurred in PIGN (1.98%) and in medulla in ascending infections (1.86%). The lowest cortical CD68+-densities were measured in thin basal membrane syndrome / Alport-syndrome (0.56%) and in medulla in immunotactoid and fibrillary glomerulopathy (0.26%). Chronic kidney disease displayed lower percentages of CD68+-densities (cortex: 1.15%; medulla: 0.49%) compared to acute kidney injury (cortex: 1.84%, p<0.001; medulla: 1.08%, p<0.001) and acute on chronic kidney injury (cortex: 1.81%, p<0.001; medulla: 1.43%, p<0.001). We detected a correlation of CD68+- and CD163+-infiltration with kidney function (eGFR) in cortex and medulla at the time of biopsy (CD68: r=-0.51 for cortex, r=-0.60 for medulla; CD163: r=-0.71 for cortex, r=-0.73 for medulla; p<0.001) and follow up (CD68: r=-0.41 for cortex, r=-0.34 for medulla, p<0.001; CD163: r=-0.46 for cortex, r=-0.50 for medulla, p<0.05). Older patients (>64 years) showed a higher medullary M2-infiltration (1.81% vs. 4.34%, p<0.005). The eGFR at the time of biopsy inversely correlated (p<0.05) with cortical CD68+-density in IgAN (r=-0.39), PIGN (r=-0.53), membranous glomerulonephritis (MGN; r=-0.70), focal segmental glomerulonephritis (r=-0.63), and hypertensive nephropathy (HNP; r=-0.44). At follow-up, this correlation (p<0.05) was still present in PIGN (r=-0.43), MGN (r=-0.58), and HNP (r=-0.77). In PIGN, cortical CD163+-density and eGFR were associated (p<0.001) at timepoint of biopsy (r=-0.51) and follow-up (r=-0.51). Particularly, cANCA-vasculitis showed a strong correlation between eGFR and cortical CD68+- as well as CD163+-densities at time of biopsy (CD68: r=-0.78; CD163: r=-0.75, p<0.001) and also for follow-up (CD68: r=-0.48; CD163: r=-0.68, p<0.05). Conclusion Macrophages may promote progression of human renal diseases, whereas monocytes do not correlate with eGFR-decline. Especially, in cANCA- vasculitis CD163+- infiltration is associated with renal outcome. Additional studies are needed to investigate, whether macrophages can serve as predictive markers or therapeutical targets in native renal diseases.


Crisis ◽  
2010 ◽  
Vol 31 (5) ◽  
pp. 238-246 ◽  
Author(s):  
Paul W. C. Wong ◽  
Wincy S. C. Chan ◽  
Philip S. L. Beh ◽  
Fiona W. S. Yau ◽  
Paul S. F. Yip ◽  
...  

Background: Ethical issues have been raised about using the psychological autopsy approach in the study of suicide. The impact on informants of control cases who participated in case-control psychological autopsy studies has not been investigated. Aims: (1) To investigate whether informants of suicide cases recruited by two approaches (coroners’ court and public mortuaries) respond differently to the initial contact by the research team. (2) To explore the reactions, reasons for participation, and comments of both the informants of suicide and control cases to psychological autopsy interviews. (3) To investigate the impact of the interviews on informants of suicide cases about a month after the interviews. Methods: A self-report questionnaire was used for the informants of both suicide and control cases. Telephone follow-up interviews were conducted with the informants of suicide cases. Results: The majority of the informants of suicide cases, regardless of the initial route of contact, as well as the control cases were positive about being approached to take part in the study. A minority of informants of suicide and control cases found the experience of talking about their family member to be more upsetting than expected. The telephone follow-up interviews showed that none of the informants of suicide cases reported being distressed by the psychological autopsy interviews. Limitations: The acceptance rate for our original psychological autopsy study was modest. Conclusions: The findings of this study are useful for future participants and researchers in measuring the potential benefits and risks of participating in similar sensitive research. Psychological autopsy interviews may be utilized as an active engagement approach to reach out to the people bereaved by suicide, especially in places where the postvention work is underdeveloped.


Author(s):  
S Wojcinski ◽  
A Farrokh ◽  
U Hille ◽  
E Hirschauer ◽  
W Schmidt ◽  
...  

1996 ◽  
Vol 35 (04) ◽  
pp. 116-121 ◽  
Author(s):  
G. E Fueger ◽  
M. Vejda ◽  
R. M. Aigner

Summary Aim: To prevent orthopedic sequelae in acute hematogenous pyogenic osteomyelitis (AHPO) of infants early diagnosis, recognition of recurrence and effective therapy is needed. This retrospective study of 47 infants with bacteriologically confirmed AHPO concerned with an analysis of the diagnostic value of systemic serum parameters compared to bone scintigraphy (BSC). Methods: AHPO was characterized initially and during the course of disease by clinical findings, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), total and differential white blood cell (WBC) count, BSC, and plain radiography. Results: CRP was the most effective serum parameter for follow- up of disease. The first sign of BSC to signal adequate response to antibiotic treatment was the decrease or normalization of hyperperfusion. Escape from therapy or poor prognosis, even when the serum parameters were normalized, was signaled by the recurrence of focal hyperperfusion and the persistent or increasing local uptake ratios on the 3-h-image over 6 weeks during a course of antibiotic treatment. Conclusion: Antibiotic treatment masks the clinical presentation, and the radiographic findings, causes non-characteristic laboratory findings, but do not prevent the scintigraphic visualization; BSC and serum parameters used in the right completion are the most successful and efficient modalities for follow-up of AHPO. Maintenance of antibiotic therapy should be done until BSC findings have reverted to normal.


2014 ◽  
Vol 1 (1) ◽  
pp. 31-36 ◽  
Author(s):  
O. Zhukorskiy ◽  
O. Gulay ◽  
V. Gulay ◽  
N. Tkachuk

Aim. To determine the response of the populations of Erysipelothrix rhusiopathiae and Leptospira interrogans pathogenic microorganisms to the impact of broadleaf cattail (Thypha latifolia) root diffusates. Methods. Aqueous solutions of T. latifolia root diffusates were sterilized by vacuum fi ltration through the fi lters with 0.2-micron pore diameter. The experimental samples contained cattail secretions, sterile water, and cultures of E. rhusiopathiae or L. interrogans. The same amount of sterile water, as in the experimental samples, was used for the purpose of control, and the same quantity of microbial cultures was added in it. After exposure, the density of cells in the experimental and control samples was determined. Results. Root diffusates of T. latifolia caused an increase in cell density in the populations of E. rhusiopathiae throughout the whole range of the studied dilutions (1:10–1:10000). In the populations of the 6 studied serological variants of L. interrogans spirochetes (pomona, grippotyphosa, copenhageni, kabura, tarassovi, canicola), the action of broadleaf cattail root diffusates caused the decrease in cell density. A stimulatory effect was marked in the experimental samples of the pollonica serological variant of leptospira. Conclusions. The populations of E. rhusiopathiae and L. interrogans pathogenic microorganisms respond to the allelopathic effect of Thypha latifolia by changing the cell density. The obtained results provide the background to assume that broadleaf cattail thickets create favorable conditions for the existence of E. rhusiopathiae pathogen bacteria. The reduced cell density of L. interrogans in the experimental samples compared to the control samples observed under the infl uence of T. latifolia root diffusates suggests that reservoirs with broadleaf cattail thickets are marked by the unfavorable conditions for the existence of pathogenic leptospira (except L. pollonica).


Author(s):  
Dheeraj Kumar Tyagi ◽  
Shivakumar .

Lifestyle disorders are one of the biggest threats for the population living unhealthy lifestyle. Sthoulya (Obesity) is one such disorder which creates lot of physical as well as mental disorder to the sufferer. Due to changing lifestyle, comforts and dietary habit lots of individuals changed their life totally. Obesity is a growing disease in developed and developing countries. Prevalence is drastically hike in past few years. Ayurveda, the science of life with which we can manage and control lots of lifestyle disorders. Focusing on dietary and lifestyle management along with treatment, we can overcome the hazards of obesity which is growing in a uncontrolled manner. The available data is based on the clinical findings only. Aim and objective: To assess the effect of “Guru Cha Atarpanam Chikitsa” in the management of Sthoulya. Setting: Swastharakshana evam Yoga, OPD and IPD, SDMCAH, Hassan. Method: Udwarthana, Parisheka, Shamana Aushadhis, Ahara, and Vihara was followed within the treatment duration and effect of treatment was assessed before and after treatment, advised for follow up. Results: The treatment adopted is effective in the management of Sthoulya and to improve the quality of life.


Author(s):  
J. Hoevelmann ◽  
E. Muller ◽  
F. Azibani ◽  
S. Kraus ◽  
J. Cirota ◽  
...  

Abstract Introduction Peripartum cardiomyopathy (PPCM) is an important cause of pregnancy-associated heart failure worldwide. Although a significant number of women recover their left ventricular (LV) function within 12 months, some remain with persistently reduced systolic function. Methods Knowledge gaps exist on predictors of myocardial recovery in PPCM. N-terminal pro-brain natriuretic peptide (NT-proBNP) is the only clinically established biomarker with diagnostic value in PPCM. We aimed to establish whether NT-proBNP could serve as a predictor of LV recovery in PPCM, as measured by LV end-diastolic volume (LVEDD) and LV ejection fraction (LVEF). Results This study of 35 women with PPCM (mean age 30.0 ± 5.9 years) had a median NT-proBNP of 834.7 pg/ml (IQR 571.2–1840.5) at baseline. Within the first year of follow-up, 51.4% of the cohort recovered their LV dimensions (LVEDD < 55 mm) and systolic function (LVEF > 50%). Women without LV recovery presented with higher NT-proBNP at baseline. Multivariable regression analyses demonstrated that NT-proBNP of ≥ 900 pg/ml at the time of diagnosis was predictive of failure to recover LVEDD (OR 0.22, 95% CI 0.05–0.95, P = 0.043) or LVEF (OR 0.20 [95% CI 0.04–0.89], p = 0.035) at follow-up. Conclusions We have demonstrated that NT-proBNP has a prognostic value in predicting LV recovery of patients with PPCM. Patients with NT-proBNP of ≥ 900 pg/ml were less likely to show any improvement in LVEF or LVEDD. Our findings have implications for clinical practice as patients with higher NT-proBNP might require more aggressive therapy and more intensive follow-up. Point-of-care NT-proBNP for diagnosis and risk stratification warrants further investigation.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1273.2-1274
Author(s):  
C. Lukas ◽  
G. Khoury ◽  
M. A. D’agostino ◽  
B. Combe ◽  
J. Morel

Background:The diagnostic process in a patient with early inflammatory back pain suggestive of axial spondyloarthritis (ax-SpA) requires assessment and integration of multiple aspects, including clinical examination, biological measurements and radiologic assessments. Among the physical examination features, alteration of spinal mobility is often observed in ax-SpA. However, whether mobility impairment might really increase diagnostic likelihood, and which of the measurements made have relevant diagnostic value remains unknown.Objectives:To describe the frequency and severity of mobility impairment in multiple traditional measurements in patients suspect of early ax-SpA at initial assessment time, and to analyze their individual diagnostic performances in reference to usual classification criteria applied after 2 years of follow-up.Methods:Data from the DESIR cohort, which included patients aged 18-50 with inflammatory back pain lasting for 3 months to 3 years and a clinical suspicion of ax-SpA diagnosis were used. Baseline measurements of Schober’s test (Schober), chest expansion (CEx), lateral spinal flexion (LatSpiFlex), cervical rotation (CervRot) and intermalleolar distance (IntMalDist) collected at baseline were classified according to reference data from the general population adjusted for age and -when appropriate- for height. Cutoffs were defined as above 2.5th, 5th, 10th and 25th percentiles. With ASAS classification for ax-SpA applied at 2 years follow-up visit as external reference, diagnostic performances (Sensitivity [Se], Specificity [Sp], Positive [PPV] and Negative [NPV] Predictive Values) were calculated.Results:Complete data were available for 575 patients (of whom 377 (66%) fulfilled the ASAS criteria at 2 years). Schober, CEx, LatSpiFlex, CervRot and IntMalDist were above 5th percentile in respectively 278 (48%), 82 (14%), 220 (38%) and 93 (16%) patients. None of the measurements showed a clinically relevant compromise between both Se and Sp, but Sp was highest for CEx-most impaired cutoffs (Figure 1). The highest PPV (73.6%) and NPV (39.4%) were observed for LatSpiFlex.Conclusion:Measures of mobility and their levels of impairment do not show sufficient individual diagnostic value for ax-SpA among patients with early inflammatory back pain. However, highest degrees of impairment when compared to general population are more specifically observed in patients finally classified with ax-SpA for CEx, which was –consistently- 1 of the 2 mobility measures that was retained in the modified New York criteria for ankylosing spondylitis.Disclosure of Interests:Cédric Lukas Speakers bureau: AbbVie; Lilly; Merck; Novartis; Pfizer; Roche-Chugai;, Consultant of: AbbVie; Bristol-Myers Squibb; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; UCB; Sanofi;, Grant/research support from: Pfizer: Novartis, Gisèle Khoury Grant/research support from: Pfizer, Maria-Antonietta d’Agostino: None declared., Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche-Chugai, Jacques Morel Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche-Chugai.


2021 ◽  
pp. 088626052110041
Author(s):  
Roos Ruijne ◽  
Cornelis Mulder ◽  
Milan Zarchev ◽  
Kylee Trevillion ◽  
Roel van Est ◽  
...  

Despite increased prevalence of domestic violence and abuse (DVA), victimization through DVA often remains undetected in mental health care. To estimate the effectiveness of a system provider level training intervention by comparing the detection and referral rates of DVA of intervention community mental health (CMH) teams with rates in control CMH teams. We also aimed to determine whether improvements in knowledge, skills and attitudes to DVA were greater in clinicians working in intervention CMH teams than those working in control teams. We conducted a cluster randomized controlled trial in two urban areas of the Netherlands. Detection and referral rates were assessed at baseline and at 6 and 12 months after the start of the intervention. DVA knowledge, skills and attitudes were assessed using a survey at baseline and at 6 and 12 months after start of the intervention. Electronic patient files were used to identify detected and referred cases of DVA. Outcomes were compared between the intervention and control teams using a generalized linear mixed model. During the 12-month follow-up, detection and referral rates did not differ between the intervention and control teams. However, improvements in knowledge, skills and attitude during that follow-up period were greater in intervention teams than in control teams: β 3.21 (95% CI 1.18-4.60). Our trial showed that a training program on DVA knowledge and skills in CMH teams can increase knowledge and attitude towards DVA. However, our intervention does not appear to increase the detection or referral rates of DVA in patients with a severe mental illness. A low detection rate of DVA remains a major problem. Interventions with more obligatory elements and a focus on improving communication between CMH teams and DVA services are recommended.


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