Transgenic Drosophila melanogaster Carrying a Human Full-Length DISC1 Construct (UAS-hflDISC1) Showing Effects on Social Interaction Networks.

Disrupted in Schizophrenia 1 (DISC1) is a scaffold protein implicated in major mental illnesses including schizophrenia, with a significant negative impact on social life. To investigate if DISC1 affects social interactions in Drosophila melanogaster, we created transgenic flies with second or third chromosome insertions of the human full-length DISC1 (hflDISC1) gene fused to a UAS promotor (UAS-hflDISC1). Initial characterization of the insertion lines showed unexpected endogenous expression of the DISC1 protein that led to various behavioral and neurochemical phenotypes. Social interaction network (SIN) analysis showed altered social dynamics and organizational structures. This was in agreement with the altered levels of the locomotor activity of individual flies monitored for 24 h. Together with a decreased ability to climb vertical surfaces, the observed phenotypes indicate altered motor functions that could be due to a change in the function of the motor neurons and/or central brain. The changes in social behavior and motor function suggest that the inserted hflDISC1 gene influences nervous system functioning that parallels symptoms of DISC1-related mental diseases in humans. Furthermore, neurochemical analyses of transgenic lines revealed increased levels of hydrogen peroxide and decreased levels of glutathione, indicating an impact of DISC1 on the dynamics of redox regulation, similar to that reported in transgenic mammals. Future studies are needed to address the localization of DISC1 expression and to address how the redox parameter changes correlate with the observed behavioral changes.

Using a Combination of Novel Research Tools to Understand Social Interaction in the Drosophila melanogaster Model for Fragile X Syndrome.

Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism spectrum disorder, is caused by a full mutation (>200 CGG repeats) in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene. Individuals with FXS experience various challenges related to social interaction (SI). Animal models, such as the Drosophila melanogaster model for FXS where the only ortholog of human FMR1 (dFMR1) is mutated, have played a crucial role in the understanding of FXS. The aim of this study was to investigate SI in the dFMR1B55 mutants (the groups of flies of both sexes simultaneously) using the novel Drosophila Shallow Chamber and a Python data processing pipeline based on social network analysis (SNA). In comparison with wild-type flies (w1118), SNA analysis in dFMR1B55 mutants revealed hypoactivity, fewer connections in their networks, longer interaction duration, a lower ability to transmit information efficiently, fewer alternative pathways for information transmission, a higher variability in the number of interactions they achieved, and flies tended to stay near the boundaries of the testing chamber. These observed alterations indicate the presence of characteristic strain-dependent social networks in dFMR1B55 flies, commonly referred to as the group phenotype. Finally, combining novel research tools is a valuable method for SI research in fruit flies.

Quality of Life of Patients with Oral Squamous Cell Carcinoma.

Background: Oral squamous cell carcinoma (OSCC) has numerous physical, psychosocial and financial implications, which significantly affect patients' quality of life. We aimed to determine the health-related quality of life (HRQoL) and identify quality of life (QoL) predictors in patients with OSCC. Methods: We included 64 consecutive patients aged 40 to 80 yr treated for OSCC from Jan to Dec 2021. Health-related QoL was evaluated using the 30-item Cancer Quality of Life Questionnaire (QLQ-C30) and the 35-item Head and Neck Cancer-Quality of Life Questionnaire (QLQ-H&N35). The demographic questionnaire and clinical parameters were also presented. Results: The functioning scale in the QLQ-C30 questionnaire with the lowest average score was Global health status. The mean QLQ-C30 summary score (80.92 ± 10.4) was higher than the Global health status score (50.5 ± 22.2). In the QLQ-H&N35 questionnaire, the symptoms with highest scores were weight loss, dry mouth, and social eating. Linear regression analysis demonstrated that Global health status score was associated with education level [ß-coefficient = 19.33 (95% CI: 10.7-24.9, P=0.004], alcohol consumption [ß-coefficient=10.04 (95% CI: 4.5-14.8), P=0.023] and invasive surgical procedure [ß-coefficient=22.75 (95% CI: 15.0-30.5), P=0.002]. The QLQ-C30 summary score was associated with living alone [ß-coefficient= -20.05 (95% CI: -29.91-(-10.21), P=0.018], smoking status [ß-coefficient=4.35 (95% CI: 1.8-6.91), P=0.043] and alcohol consumption [ß-coefficient =4.59 (95% CI: 1.99-7.19), P=0.037]. Conclusion: We found several significant predictors of worse perception of HRQoL among patients with OSCC, which may be useful for specific prevention and treatment in order to achieve better QoL.

Melatonin Action in Type 2 Diabetic Parotid Gland and Dental Pulp: In Vitro and Bioinformatic Findings.

Type 2 diabetes mellitus (T2DM) is associated with functional deterioration of the salivary gland and dental pulp, related to oxidative stress. The aim was to integrate experimental and bioinformatic findings to analyze the cellular mechanism of melatonin (MEL) action in the human parotid gland and dental pulp in diabetes. Human parotid gland tissue was obtained from 16 non-diabetic and 16 diabetic participants, as well as human dental pulp from 15 non-diabetic and 15 diabetic participants. In human non-diabetic and diabetic parotid gland cells (hPGCs) as well as in dental pulp cells (hDPCs), cultured in hyper- and normoglycemic conditions, glial cell line-derived neurotrophic factor (GDNF), MEL, inducible nitric oxide synthase (iNOS) protein expression, and superoxide dismutase (SOD) activity were measured by enzyme-linked immunosorbent assay (ELISA) and spectrophotometrically. Bioinformatic analysis was performed using ShinyGO (v.0.75) application. Diabetic participants had increased GDNF and decreased MEL in parotid (p < 0.01) and dental pulp (p < 0.05) tissues, associated with increased iNOS and SOD activity. Normoglycemic hDPCs and non-diabetic hPGCs treated with 0.1 mM MEL had increased GDNF (p < 0.05), while hyperglycemic hDPCs treated with 1 mM MEL showed a decrease in up-regulated GDNF (p < 0.05). Enrichment analyses showed interference with stress and ATF/CREB signaling. MEL induced the stress-protective mechanism in hyperglycemic hDPCs and diabetic hPGCs, suggesting MEL could be beneficial for diabetes-associated disturbances in oral tissues.

Immediate placement of extra-short implants in refined scapula tip microvascular free flaps: In house virtual planning and surgical technique - Proof of concept.

Scapula tip flaps have been introduced in the literature as an ideal surgical treatment option for large defects in the horizontal plane of the maxilla. This article aims to present a unique step by step protocol for a near total maxillectomy with a pterygoid bone resection and consecutive microvascular reconstruction with a harvested scapula tip flap. The protocol includes immediate placement of extra-short implants in donor bone with the aid of Virtual Surgical Planning (VSP), and an in-house 3D printing of medical 3D models and surgical guides. So far, there has been no presented surgical technique combining immediate implant placement in the scapula region with simultaneous microvascular repair. This technique allows: tumour resection; flap harvesting; extra-short implant placements and reconstruction to be performed in one simultaneous procedure. The technique is presented with illustrations, VSP (presented on videos), radiographs, and surgical findings. We discovered that this refinement of the scapula tip surgery has enabled reconstructive procedures to be performed at the same time as implant placements, providing expedited functional and aesthetic outcomes in selected cases. Moreover, modification of the surgical technique could enhance the competence of the oropharyngeal edge. In conclusion, this new surgical protocol utilizing VSP, 3D models and simultaneous extra-short implant placement provides indispensable advantages for such a complicated surgical procedures, while significantly shortening the duration of surgery.

A network-based analysis detects cocaine-induced changes in social interactions in Drosophila melanogaster.

Addiction is a multifactorial biological and behavioral disorder that is studied using animal models, based on simple behavioral responses in isolated individuals. A couple of decades ago it was shown that Drosophila melanogaster can serve as a model organism for behaviors related to alcohol, nicotine and cocaine (COC) addiction. Scoring of COC-induced behaviors in a large group of flies has been technologically challenging, so we have applied a local, middle and global level of network-based analyses to study social interaction networks (SINs) among a group of 30 untreated males compared to those that have been orally administered with 0.50 mg/mL of COC for 24 hours. In this study, we have confirmed the previously described increase in locomotion upon COC feeding. We have isolated new network-based measures associated with COC, and influenced by group on the individual behavior. COC fed flies showed a longer duration of interactions on the local level, and formed larger, more densely populated and compact, communities at the middle level. Untreated flies have a higher number of interactions with other flies in a group at the local level, and at the middle level, these interactions led to the formation of separated communities. Although the network density at the global level is higher in COC fed flies, at the middle level the modularity is higher in untreated flies. One COC specific behavior that we have isolated was an increase in the proportion of individuals that do not interact with the rest of the group, considered as the individual difference in COC induced behavior and/or consequence of group influence on individual behavior. Our approach can be expanded on different classes of drugs with the same acute response as COC to determine drug specific network-based measures and could serve as a tool to determinate genetic and environmental factors that influence both drug addiction and social interaction.

Axon morphogenesis and maintenance require an evolutionary conserved safeguard function of Wnk kinases antagonizing Sarm and Axed.

The molecular and cellular mechanisms underlying complex axon morphogenesis are still poorly understood. We report a novel, evolutionary conserved function for the Drosophila Wnk kinase (dWnk) and its mammalian orthologs, WNK1 and 2, in axon branching. We uncover that dWnk, together with the neuroprotective factor Nmnat, antagonizes the axon-destabilizing factors D-Sarm and Axundead (Axed) during axon branch growth, revealing a developmental function for these proteins. Overexpression of D-Sarm or Axed results in axon branching defects, which can be blocked by overexpression of dWnk or Nmnat. Surprisingly, Wnk kinases are also required for axon maintenance of adult Drosophila and mouse cortical pyramidal neurons. Requirement of Wnk for axon maintenance is independent of its developmental function. Inactivation of dWnk or mouse Wnk1/2 in mature neurons leads to axon degeneration in the adult brain. Therefore, Wnk kinases are novel signaling components that provide a safeguard function in both developing and adult axons.

Cardiopulmonary assessment of patients diagnosed with Gaucher's disease type I.

BACKGROUND: Understanding the basis of the phenotypic variation in Gaucher's disease (GD) has proven to be challenging for efficient treatment. The current study examined cardiopulmonary characteristics of patients with GD type 1. METHODS: Twenty Caucasian subjects (8/20 female) with diagnosed GD type I (GD-S) and 20 age- and sex-matched healthy controls (C), were assessed (mean age GD-S: 32.6 ± 13.1 vs. C: 36.2 ± 10.6, p > .05) before the initiation of treatment. Standard echocardiography at rest was used to assess left ventricular ejection fraction (LVEF) and pulmonary artery systolic pressure (PASP). Cardiopulmonary exercise testing (CPET) was performed on a recumbent ergometer using a ramp protocol. RESULTS: LVEF was similar in both groups (GD-S: 65.1 ± 5.2% vs. C: 65.2 ± 5.2%, p > .05), as well as PAPS (24.1 ± 4.2 mmHg vs. C: 25.5 ± 1.3 mmHg, p > .05). GD-S had lower weight (p < .05) and worse CPET responses compared to C, including peak values of heart rate, oxygen consumption, carbondioxide production (VCO2 ), end-tidal pressure of CO2 , and O2 pulse, as well as HR reserve after 3 min of recovery and the minute ventilation/VCO2  slope. CONCLUSIONS: Patients with GD type I have an abnormal CPET response compared to healthy controls likely due to the complex pathophysiologic process in GD that impacts multiple systems integral to the physiologic response to exercise.

Locomotor sensitization modulates voluntary self-administration of methamphetamine in Drosophila melanogaster.

As complexities of addictive behaviors cannot be fully captured in laboratory studies, scientists use simple addiction-associated phenotypes and measure them in laboratory animals. Locomotor sensitization, characterized by an increased behavioral response to the same dose of the drug, has been extensively used to elucidate the genetic basis and molecular mechanisms of neuronal plasticity. However, to what extent it contributes to the development of addiction is not completely clear. We tested if the development of locomotor sensitization to methamphetamine affects voluntary self-administration, and vice versa, in order to investigate how two drug-associated phenotypes influence one another. In our study, we used the genetically tractable model organism, Drosophila melanogaster, and quantified locomotor sensitization and voluntary self-administration to methamphetamine using behavioral tests that were developed and adapted in our laboratory. We show that flies express robust locomotor sensitization to the second dose of volatilized methamphetamine, which significantly lowers preferential self-administration of methamphetamine. Naive flies preferentially self-administer food with methamphetamine over plain food. Exposing flies to volatilized methamphetamine after voluntary self-administration abolishes locomotor sensitization. We tested period null (per01 ) mutant flies and showed that they do not develop locomotor sensitization, nor do they show preferential self-administration of methamphetamine. Our results suggest that there may be partially overlapping neural circuitry that regulates the expression of locomotor sensitization and preferential self-administration to methamphetamine and that this circuitry requires a functional per gene.

Motor vehicle accidents-related maxillofacial injuries: a multicentre and prospective study.

OBJECTIVES: The purpose of this European multicenter prospective study was to obtain more precise information about the demographic characteristics and etiologic/epidemiologic patterns of motor vehicle accidents (MVA)-related maxillofacial fractures. STUDY DESIGN: Of the 3260 patients with maxillofacial fractures admitted within the study period, 326 traumas were caused by MVAs with a male/female ratio of 2.2:1. RESULTS: The maximum incidence was found in Zagreb (Croatia) (18%) and the minimum in Bergen (Norway) (0%). The most frequent mechanisms were car accidents, with 177 cases, followed by motorcycle accidents. The most frequently observed fracture involved the mandible, with 199 fractures, followed by maxillo-zygomatic-orbital (MZO) fractures. CONCLUSIONS: In all the 3 groups (car, motorcycle, and pedestrian), mandibular and MZO fractures were the 2 most frequently observed fractures, with some variations. The importance of analyzing MVA-related facial injuries and their features and characteristics should be stressed.

Medication-Related Osteonecrosis of the Jaws: Two Center Retrospective Cohort Studies.

This retrospective cohort study aims to describe characteristics of patients with MRONJ, to identify factors associated with MRONJ development, and to examine variables associated with favourable outcome. Totally 32 patients were followed and observed: 21 females and 11 males, in the age range 35-84 in the period from 2009 to 2018. Clinical, radiological examination (Orthopantomograph and CBCT) and biopsy were performed in order to achieve diagnosis. Demographic and clinical variables were taken into consideration: sex, age, primary disease, medication type, mode of delivery, anatomic location, drug treatment duration, timing of tooth extraction, chemotherapy, presence of bone metastasis, aetiology of MRONJ, disease stage, and treatment modality. MRONJ developed under osteoporosis and malignant disease in 11 and 21 patients, respectively. MRONJ development was triggered by tooth extraction or trauma in 30 out of 32 cases, whereas the two patients developed MRONJ spontaneously. Stages I, II, and III were confirmed in 5 (16%), 18 (58%), and 9 (28%) patients, respectively. Mandible was affected in 23 (72%) patients. MRONJ was treated in our department by conservative and surgical modality. In this study we found that 65% of all patients were classified in the cured/improvement group and 35% in the stable/progression group. The female gender, osteoporosis as primary disease, oral regime intake, shorter period on BPs, earlier stage of disease, and specific anatomic localisation (frontal and premolar maxilla) were factors associated with better response to therapy and favourable clinical outcome. Comprehensive treatment protocol and further randomized studies are necessary for further improvements.

Dual Roles of the Mineral Metabolism Disorders Biomarkers in Prevalent Hemodilysis Patients: In Renal Bone Disease and in Vascular Calcification.

BACKGROUND: Vascular calcification (VC) is highly prevalent in dialysis (HD) patients, and its mechanism is multifactorial. Most likely that systemic or local inhibitory factor is overwhelmed by promoters of VC in these patients. VC increased arterial stiffness, and left ventricular hypertrophy. Thus, the present study aimed to investigate the association of VC and myocardial remodeling and to analyze their relationship with VC promoters (fibroblast growth factor 23-FGF23, Klotho, intact parathormon-iPTH, vitamin D) in 56 prevalent HD patients (median values: age 54 yrs, HD vintage 82 months). METHODS: Besides routine laboratory analyzes, serum levels of FGF 23, soluble Klotho, iPTH, 1,25-dihydroxyvitamin D3; pulse wave velocity (PWV); left ventricular (LV) mass by ultrasound; and VCs score by Adragao method were measured. RESULTS: VC was found in 60% and LV concentric or eccentric hypertrophy in 50% patients. Dialysis vintage (OR 1.025, 95%CI 1.007-1.044, p=0.006) FGF23 (OR 1.006, 95% CI 0.992-1.012, p=0.029) and serum magnesium (OR 0.000, 95%CI 0.000-0.214, p=0.04) were associated with VC. Changes in myocardial geometry was associated with male sex (beta=-0.273, 95% CI -23.967 1.513, p=0.027), iPTH (beta 0.029, 95%CI -0.059-0.001, p=0.027) and vitamin D treatment (beta 25.49, 95%CI 11.325-39.667, p=0.001). Also, patients with the more widespread VC had the highest LV remodeling categories. PWV was associated patient's age, cholesterol, diastolic blood pressure, LV mass (positively) and serum calcium (negatively), indicating potential link with atherosclerotic risk. CONCLUSIONS: Despite to different risk factors for VC and myocardial remodeling, obtained results could indicate that risk factors intertwine in long-term treatment of HD patients and therefore careful and continuous correction of mineral metabolism disorders is undoubtedly of the utmost importance.

The "European zygomatic fracture" research project: The epidemiological results from a multicenter European collaboration.

PURPOSE: Fractures of the zygomaticomaxillary complex (ZMC) are common injuries that may lead to loss of an aesthetically pleasing appearance and functional impairment. The aim of this study was to analyze the demographics, causes, characteristics, and outcomes of zygomatic fractures managed at several European departments of oral and maxillofacial surgery. MATERIALS AND METHODS: This study is based on a multicenter systematic database that allowed the recording of all patients with ZMC fractures between 1 January 2013 and 31 December 2017. The following data were recorded: gender, age, personal medical history, etiology, side of zygomatic fracture, classification of ZMC fracture, associated maxillofacial fractures, symptoms at diagnosis, type of performed treatment, and sequelae/complications. RESULTS: A total of 1406 patients (1172 males, 234 females) were included in the study. Statistically significant correlations were found between assault-related ZMC fractures and the A3 class (p < .0000005) and between Infraorbital Nerve (ION) anesthesia and B class (p < .00000005). CONCLUSION: The most frequent cause of ZMC fractures was assault, followed by falls. The most frequently involved decade of age was between 20 and 29 years. The decision and type of surgical treatment of ZMC fractures depends on several issues that need to be considered on a case by case basis.

Characterization of stem-like cancer cells in basal cell carcinoma and its surgical margins.

BACKGROUND: Understanding the pathogenesis of basal cell carcinoma (BCC) and identifying the cells responsible for propagation and recurrence are crucial for the development of new treatment strategies. The aim of this study was to characterize the cells isolated from BCC and its margin. METHODS: Primary cultures were established from 10 BCCs, their respective close resection margins (3 mm) and 10 control tissues. Stem cell markers analysis was carried out by real-time PCR and/or flow cytometry. Spheroid formation and MTT assays were also performed. RESULTS: Real-time PCR showed a higher expression of embryonic (Oct4, Sox2 and Nanog) and mesenchymal (CD44 and CD73) stem cell markers in tumors compared to margins and controls (P < 0.05). Bmi-1 and GPR49 were also upregulated in tumors in comparison with margins. Both tumor and margin cells, but not normal, had the capacity to form spheroids. During passages, the number of spheres increased, while the diameter decreased. Tumor cells showed higher chemo-resistance compared to margin and control cells. CONCLUSIONS: Basal cell carcinomas expressed stem cell markers, pointing to the existence of a cancer cell side population with stemness characteristics. Margin also appeared to harbour a small number of cancer-initiating cells.

Putative cancer stem cells are present in surgical margins of oral squamous cell carcinoma.

PURPOSE: Recent evidence suggests that small subpopulations of stem-like cells are accountable for tumour initiation, progression and metastasis. Until now, studies were focused exclusively on the characterization of these cell populations within the tumour itself, while tumour margins were neglected, although it is known that the histological and molecular status of tumour margins may play a significant role in the course of the disease. Therefore, the aims of the study were to isolate cells from oral squamous cell carcinomas and their respective margins, to characterize these cells using specific markers, to assess their self-renewal potential and determine their chemoresistance. METHODS: Cell cultures were obtained from 12 tissue specimens (6 tumours and 6 margins). Total RNA was extracted and gene expression analysis was done by real-time PCR (RT-PCR). Flow cytometry, immunocytometry, sphere formation and MTT assays were also applied. RESULTS: With minor differences, cells originating from both tumours and tumour margins showed the presence of stem cell markers CD133, Nanog, Sox2, CD44, and Oct4, had the capacity to form spheroids and showed chemoresistance. CONCLUSIONS: Subpopulations of margin cells appeared to have stemness properties which might raise the question of re-evaluation of optimal surgical management.

The relationship between causative microorganisms and cardiac lesions caused by infective endocarditis: New perspectives from the contemporary cohort of patients.

BACKGROUND: The etiology of infective endocarditis (IE) is changing. More aggressive forms with multiple IE cardiac lesions have become more frequent. This study sought to explore the relationship between contemporary causative microorganisms and IE cardiac lesions and to analyze the impact of multiple lesions on treatment choice. METHODS: In 246 patients hospitalized for IE between 2008 and 2015, cardiac lesions caused by IE were analyzed by echocardiography, classified according to the 2015 European Society of Cardiology guidelines and correlated with microbiological data. We defined a new parameter, the Echo IE Sum, to summarize all IE cardiac lesions in a single patient, enabling comprehensive comparisons between different etiologies and treatment strategies. RESULTS: Staphylococcus aureus was associated with the development of large vegetation (OR 2.442; 95% CI 1.220-4.889; p=0.012), non-HACEK bacteria with large vegetation (OR 13.662; 95% CI 2.801-66.639; p=0.001), perivalvular abscess or perivalvular pseudoaneurysm (OR 5.283; 95% CI 1.069-26.096; p=0.041), and coagulase-negative staphylococci (CoNS) with leaflet abscess or aneurysm (OR 3.451; 95% CI 1.285-9.266, p=0.014), and perivalvular abscess or perivalvular pseudoaneurysm (OR 4.290; 95% CI 1.583-11.627; p=0.004). The Echo IE Sum significantly differed between different etiologies (p<0.001), with the highest value in non-HACEK and the lowest in streptococcal endocarditis. Patients operated for IE had a significantly higher Echo IE Sum vs those who were medically treated (p<0.001). CONCLUSION: None of the IE cardiac lesions is microorganism-specific. However, more severe lesions were caused by S. aureus, CoNS, and non-HACEK bacteria. The highest propensity to develop multiple lesions was shown by the non-HACEK group. Higher Echo IE Sum in patients sent to surgery emphasized the importance of multiple IE cardiac lesions on treatment choice and potential usage of Echo IE Sum in patient management.

Stress hormones at rest and following exercise testing predict coronary artery disease severity and outcome.

OBJECTIVES: Despite considerable knowledge regarding the importance of stress in coronary artery disease (CAD) pathogenesis, its underestimation persists in routine clinical practice, in part attributable to lack of a standardized, objective assessment. The current study examined the ability of stress hormones to predict CAD severity and prognosis at basal conditions as well as during and following an exertional stimulus. MATERIALS AND METHODS: Forty Caucasian subjects with significant coronary artery lesions (≥50%) were included. Within 2 months of coronary angiography, cardiopulmonary exercise testing (CPET) on a recumbent ergometer was performed in conjunction with stress echocardiography (SE). At rest, peak and after 3 min of recovery following CPET, plasma levels of cortisol, adrenocorticotropic hormone (ACTH) and NT-pro-brain natriuretic peptide (NT-pro-BNP) were measured by immunoassay sandwich technique, radioimmunoassay, and radioimmunometric technique, respectively. Subjects were subsequently followed a mean of 32 ± 10 months. RESULTS AND DISCUSSION: Mean ejection fraction was 56.7 ± 9.6%. Subjects with 1-2 stenotic coronary arteries (SCA) demonstrated a significantly lower plasma cortisol levels during CPET compared to those with 3-SCA (p < .05), whereas ACTH and NT-pro-BNP were not significantly different (p > .05). Among CPET, SE, and hormonal parameters, cortisol at rest and during CPET recovery demonstrated the best predictive value in distinguishing between 1-, 2-, and 3-SCA [area under ROC curve 0.75 and 0.77 (SE = 0.11, 0.10; p = .043, .04) for rest and recovery, respectively]. ΔCortisol peak/rest predicted cumulative cardiac events (area under ROC curve 0.75, SE = 0.10, p = .049). CONCLUSIONS: Cortisol at rest and following an exercise test holds predictive value for CAD severity and prognosis, further demonstrating a link between stress and unwanted cardiac events.

N-terminal pro-brain natriuretic peptide is related with coronary flow velocity reserve and diastolic dysfunction in patients with asymmetric hypertrophic cardiomyopathy.

BACKGROUND: The relations of elevated N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac ischemia in hypertrophic cardiomyopathy (HCM) patients is uncertain. Therefore we designed the study with the following aims: (1) to analyze plasma concentrations of NT-pro-BNP in various subsets of HCM patients; (2) to reveal the correlations of NT-pro-BNP, myocardial ischemia, and diastolic dysfunction; (3) to assess predictors of the elevated plasma levels of NT-pro-BNP. METHODS AND RESULTS: In 61 patients (mean age 48.9±16.3 years; 26 male) with asymmetric HCM plasma levels of NT-pro-BNP were obtained. Standard transthoracic examination, tissue Doppler echocardiography with measurement of transthoracic coronary flow velocity reserve (CFVR) in left anterior descending artery (LAD) was done. Mean natural logarithm value of NT-pro-BNP was 7.11±0.95pg/ml [median value 1133 (interquartile range 561-2442)pg/ml]. NT-pro-BNP was significantly higher in patients with higher NYHA class, in obstructive HCM, more severe mitral regurgitation, increased left atrial volume index (LAVI), presence of calcified mitral annulus, elevated left ventricular (LV) filling pressure and in decreased CFVR. Levels of NT-pro-BNP significantly correlated with the ratio of E/e' (r=0.534, p<0.001), LV outflow tract gradient (r=0.503, p=0.024), LAVI (r=0.443, p<0.001), while inversely correlated with CFVR LAD (r=-0.569, p<0.001). When multivariate analysis was done only CFVR LAD and E/e' emerged as independent predictors of NT-pro-BNP. CONCLUSION: Plasma levels of NT-pro-BNP were significantly higher in HCM patients with more advanced disease. Elevated NT-pro-BNP not only reflects the diastolic impairment of the LV, but it might also be the result of cardiac ischemia in patients with HCM.

Gauging the response to cardiac resynchronization therapy: The important interplay between predictor variables and definition of a favorable outcome.

AIMS: Selection of patients who are viable candidates for cardiac resynchronization therapy (CRT), prediction of the response to CRT as well as an optimal definition of a favorable response, all require further exploration. The purpose of this study was to evaluate the interplay between the prediction of the response to CRT and the definition of a favorable outcome. METHODS: Seventy patients who received CRT were included. All patients met current guideline criteria for CRT. Forty-three echocardiographic parameters were evaluated before CRT and at 1, 3, 6, and 12 months. M-mode, 2D echocardiography, and Doppler imaging were used to quantify left ventricular (LV) systolic and diastolic function, mitral regurgitation, right ventricular systolic function, pulmonary artery pressure, and myocardial mechanical dyssynchrony. The following definitions of a favorable CRT response were used: left ventricular ejection fraction (LVEF) improvement more >5% acutely following CRT, LVEF improvement >20% at 12-month follow-up, and a LV end-systolic volume (LVESV) decrease >15% at 12-month follow-up. RESULTS: For the LVEF improvement >5%, the best predictor was isovolumetric relaxation time (IVRT; P=.035). For improvement of LVEF >20%, the best predictors were left ventricular stroke index (LVSI; P=.044) and left ventricular fractional shortening (LVFS; P=.031). For the drop in left ventricular systolic volume (LVESV >15%), the best predictor was septal-to-lateral wall delay (ΔT) (P=.043, RR=1.023, 95% CI for RR=1.001-1.045). CONCLUSION: The definition of a favorable CRT response influenced the optimal predictor variable(s). Standardization of defining a favorable response to CRT is needed to guide clinical decision making processes.