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Background: Cadmium-zinc-telluride (CZT)-based detectors exhibit higher diagnostic sensitivity in myocardial perfusion imaging (MPI) than conventional Anger-MPI for detection of coronary artery disease (CAD); however, reduced specificity and diagnostic accuracy of CZT-MPI were observed. This study aims to compare these different camera systems and to examine the degree of inter-rater reproducibility among readers with varying experience in MPI., Methods: 83 patients who underwent double stress/rest examinations using both a CZT and conventional SPECT cameras within one visit were included. Anonymized and randomized MPI-images were distributed to 15 international readers using a standardized questionnaire. Subsequent coronary angiography findings of ten patients served as a reference for analysis of sensitivity and specificity., Results: Image quality was significantly better in CZT-MPI with significantly lower breast attenuation (P < 0.05). CZT-MPI exhibited higher sensitivity than Anger-MPI (87.5% vs. 62.5%) and significantly reduced specificity (40% vs. 100%). Readers experienced with both camera systems had the highest inter-rater agreement indicating higher reproducibility (CZT 0.54 vs. conv. 0.49, P < 0.05)., Conclusions: Higher diagnostic sensitivity of CZT-MPI offers advantages in detection of CAD yet potentially of at the cost of reduced specificity, therefore it requires special training and a differentiated evaluation approach, especially for non-experienced readers with such camera systems., (© 2022. The Author(s).)

Several environmental and genetic factors have been found to influence the development and progression of coronary artery disease (CAD). Although the effects of the environmental hazards on CAD pathophysiology are well documented, the genetic architecture of the disease remains quite unclear. A number of single-nucleotide polymorphisms have been identified based on the results of the genome-wide association studies. However, there is a lack of strong evidence regarding molecular causality. The minority of the reported predisposing variants can be related to the conventional risk factors of CAD, while most of the polymorphisms occur in non-protein-coding regions of the DNA. However, independently of the specific underlying mechanisms, genetic information could lead to the identification of a population at higher genetic risk for the long-term development of CAD. Myocardial single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are functional imaging techniques that can evaluate directly myocardial perfusion, and detect vascular and/or endothelial dysfunction. Therefore, these techniques could have a role in the investigation of the underlying mechanisms associated with the identified predisposing variants, advancing our understanding regarding molecular causality. In the population at higher genetic risk, myocardial SPECT or PET could provide important evidence through the early depiction of sub-clinical dysfunctions, well before any atherosclerosis marker could be identified. Notably, SPECT and PET techniques have been already used for the investigation of the functional consequences of several CAD-related polymorphisms, as well as the response to certain treatments (statins). Furthermore, therefore, in the clinical setting, the combination of genetic evidence with the findings of myocardial SPECT, or PET, functional imaging techniques could lead to more efficient screening methods and may improve decision making with regard to the diagnostic investigation and patients' management., (© 2020. American Society of Nuclear Cardiology.)

Background: Renin-angiotensin-aldosterone system (RAAS) has an important role in atherosclerosis. We investigated the effects of six RAAS gene polymorphisms on myocardial perfusion., Methods and Results: We examined 810 patients with known or suspected coronary artery disease (CAD) using stress-rest myocardial single-photon emission computed tomography. Summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), transient ischemic dilation (TID), and lung/heart ratio (LHR) were recorded. The following gene polymorphisms were investigated: angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M235T and T174M, angiotensin II type 1 receptor (AT1R) A1166C, renin (REN) C5312T, and angiotensin II type 2 receptor (AT2R) C3123A. The heterozygotes or homozygotes on ACE D allele were 7.54 times more likely to have abnormal SSS, while the AGT (T174M) heterozygotes were 5.19 times more likely to have abnormal SSS. The homozygotes of ACE D had significantly higher values on TID and LHR, while the AGT (T174M) heterozygotes had higher values on TID. The AT1R heterozygotes had greater odds for having SSS ≥ 3. The patients carried AT1R homozygosity of C allele had significantly higher values on TID, while heterozygotes of AT1R had significantly higher values on LHR., Conclusions: Among the polymorphisms investigated, ACE D allele had the strongest association with abnormal myocardial perfusion.

Background: The aim of the present study was to compare Emory Cardiac Toolbox, Myovation, and Quantitative Gated SPECT software regarding the automatic measurements of perfusion and functional left ventricular (LV) quantitative parameters, summed stress score (SSS), perfusion defect score, LV ejection fraction (LVEF), end-diastolic volume, and end-systolic volume (ESV)., Methods and Results: 99 mTc-tetrofosmin gated SPECT studies were performed in 634 consecutive patients based on the one-day stress/rest protocol. Participants were divided into subgroups according to heart size (ESV cut-off value: 25 mL), perfusion (SSS >/≤3), and other patient/protocol-related factors. LVEF was categorized as normal (≥50%), mildly moderately impaired (35-49%), and severely abnormal (<35%). The concordance between the packages was good to excellent, in overall population, ESV ≤25 mL, ESV >25 mL, and SSS >3 subgroups (intraclass correlation coefficients, ICCs 0.73-0.93). In SSS ≤3 subgroup, the correlation was excellent for LV functional parameters, but suboptimal for perfusion variables (ICCs 0.30-0.83). LVEF categorization revealed similar variability (discordance 18.1 and 11.1% for stress/rest LVEF values, respectively). Pair comparisons demonstrated considerable differences concerning all parameters for all patient subgroups. The statistical significance of our findings by ESV and SSS classifications was evaluated., Conclusions: Despite the significant concordance between software packages, considerable differences in mean values of myocardial perfusion and LV functional parameters were demonstrated.

Purpose: MLH3, a MutL homolog protein in mammals playing a role in DNA mismatch repair, is associated with spermatogenesis and male infertility. The purpose of the present study was to investigate the association of the single-nucleotide polymorphism (SNP), rs 175080 in the MLH3 gene, with sperm parameters in a Greek population., Methods: The study included 300 men of couples undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) treatments (years 2011-2013). Genomic DNA was extracted from 300 peripheral blood samples, and conventional quantitative real-time PCR was performed for genotyping. Of them, 122 were from men used as "controls" and 178 from men used as "cases." Allocation to the two groups was based on sperm concentrations (≥15 and <15 million/ml, respectively). Serum FSH, LH, estradiol, testosterone, and prolactin concentrations as well as sperm parameters were compared between three genotypes (GG, GA, and AA). Furthermore, the frequencies of these three genotypes were compared between "cases" and "controls.", Results: Anthropometric parameters and hormonal values did not differ significantly between the three genotypes. Significantly lower sperm concentrations were found in men with the AA genotype as compared to men with the GG and GA genotypes (p < 0.001). The AA genotype had the lower progressive motility values as compared to the other two genotypes (p < 0.05). Also, there was a significantly different distribution of the frequencies of the three genotypes between "cases" and "controls" (p < 0.001)., Conclusions: It is suggested that the studied SNP in the MLH3 gene may be linked to oligozoospermia in Caucasian men of a certain area.

Purpose: To determine if there is any effect of AMH and BMP-15 on estradiol and progesterone production from primary-cultured human luteinizing granulosa cells, to delineate what is the effect of FSH on their actions and which are the possible mechanisms involved., Methods: Luteinizing granulosa cells (GCs), obtained from follicular fluid of 30 women undergoing in vitro fertilization, were cultured, after a short 24-h preincubation period, in serum-free medium for 24 or/and 48 h in the presence/absence of various concentrations of AMH, BMP-15 and FSH alone or in combinations. Estradiol and progesterone production, SMAD5 phosphorylation and StAR expression were studied in parallel. Steroids were measured in culture-supernatant using enzyme-immunoassays, while Smad5-signaling pathway activation and StAR protein expression were assessed immunocytochemically., Result(s): We found that the treatment of AMH in GCs for 24/48 h attenuated FSH-induced estradiol production (p < 0.001), had no effect on basal estradiol levels, decreased basal progesterone production (p < 0.001) and FSH-induced StAR expression (p < 0.001). On the other hand, BMP-15 decreased basal estradiol levels (p < 0.001) and attenuated FSH-induced estradiol production (p < 0.001). Furthermore, BMP-15 reduced progesterone basal secretion (p < 0.001), an effect that was partially reversed by FSH (p < 0.01), probably via increasing StAR expression (p < 0.001). FSH-induced StAR expression was also attenuated by BMP-15 (p < 0.001). FSH, AMH and BMP-15 activated Smad-signaling pathway, as confirmed by the increase of phospo-Smad5 protein levels (p < 0.001 compared to control)., Conclusion(s): AMH and BMP-15 by interacting with FSH affect the production of estradiol and progesterone from cultured luteinizing-granulosa cells possibly via Smad5-protein phosphorylation.

Adiponectin, the most abundant adipose-released cytokine, has an important role in metabolism, primarily through reducing insulin resistance. Reproductive functions are known to be influenced by energy balance and adiponectin may be involved in the underlying mechanisms connecting reproduction and metabolism. Interestingly, adiponectin has been shown to exert actions in the female reproductive system, including the hypothalamic-pituitary-ovarian axis and the endometrium. The peripheral effects of this adipocytokine are mediated mainly via 2 receptors, AdipoR1 and AdipoR2. The expression of these receptors has been reported in the brain, ovaries, endometrium, and the placenta. Thus, adiponectin may influence fertility and pregnancy. Furthermore, adiponectin concentrations and effects have been assessed in some pregnancy-associated disorders and gynecological conditions. The findings may lead to the use of adiponectin or its receptors as therapeutic targets in novel treatment strategies of these disorders.

Adipokines have a significant effect on metabolism, immunoinflammatory responses as well as on carcinogenesis; therefore, we aimed at evaluating their potential predictive and prognostic significance in lung cancer. Eighty patients--mean age 62.9 ± 9.2 years--with previously untreated lung cancer (61 NSCLC and 19 SCLC) of all stages and 40 healthy individuals were enrolled in this study. Serum levels of leptin, adiponectin and ghrelin were measured using human Radioimmunoassay kits. Serum leptin levels in lung cancer patients were lower compared to control (p < 0.0001), while adiponectin and ghrelin levels were significantly increased in patients (p = 0.0003 and p = 0.0043, respectively). Additionally, the leptin/adiponectin ratio was significantly lower in the patients group compared to controls (p < 0.0001]. There was no association between serum levels of adipokines and any of the patient clinicopathological characteristics or response to therapy. Nevertheless, patients with lower values of serum leptin had shorter overall survival (p = 0.014), whereas multivariate analysis revealed leptin levels as an independent prognostic factor for survival (p = 0.024, HR 0.452, CI 95 % 0.232-0.899). These results suggest that adipokines may play a role in the pathogenesis of lung cancer, while leptin serum levels might provide useful prognostic information.

Ghrelin is considered the endogenous ligand of growth hormone secretagogue receptor type 1a, and its modulatory actions have been demonstrated in a large array of endocrine and nonendocrine functions. According to recent studies, ghrelin seems to act at different levels of the reproductive system, exerting predominantly inhibitory effects on mammalian reproduction. It has been shown to influence the reproductive system by regulating hormone secretion from the brain and by acting directly on the gonads to affect tissue development and steroidogenesis. Thus, the endocrine network, which integrates energy balance and fertility, might involve ghrelin. Furthermore, ghrelin levels and actions have been assessed in various female reproductive system disorders. The findings could lead to a better understanding of the pathogenesis of these disorders and, possibly, to more beneficial therapeutic strategies.

Background: Administration of ghrelin to women stimulates the secretion of PRL but the mechanism is not known., Aim: The aim of the study was to investigate the effect of the dopamine receptor blocker, metoclopramide, on ghrelin-induced PRL release., Subjects and Methods: Ten healthy normally cycling women were studied in the midluteal phase of 4 menstrual cycles. A single dose of normal saline (cycle 1), ghrelin (1 μg/kg) (cycle 2), metoclopramide (20 mg) (cycle 3), and ghrelin plus metoclopramide (cycle 4) was given to the women iv. Blood samples in relation to the iv injection (time 0) were taken at -15, 0, 15, 30, 45, 60, 75, 90, and 120 min. The response of PRL and GH was assessed., Results: Following ghrelin administration (cycles 2 and 4), plasma ghrelin and serum PRL and GH levels increased rapidly, peaking at 30 min (p<0.001). PRL was also increased after the injection of metoclopramide (p<0.001, cycle 3), but the increase was much greater than after the administration of ghrelin. The combination of ghrelin and metoclopramide stimulated PRL secretion to the same extent with metoclopramide alone. No changes in GH and PRL levels were seen after saline injection., Conclusions: These results demonstrate that the stimulating effect of ghrelin on PRL secretion is not additive with that of metoclopramide, although a dose range study might provide further information.

Ghrelin is a novel GH-releasing peptide, which has been identified as an endogenous ligand for GH-secretagogue receptor. Ghrelin is mainly secreted by the stomach and plays a critical role in a variety of physiological processes including endocrine, metabolic, cardiovascular, immunological, and other actions. Ghrelin stimulates food intake via hypothalamic neurons and causes a positive energy balance and body weight gain by decreasing fat utilization and promoting adiposity. Given the multiple effects of ghrelin, its potential clinical applications have been evaluated in various conditions. Preliminary trials have shown that it may prove valuable in the management of disease-induced cachexia. Ghrelin may improve the wasting syndrome through GH-dependent or GH-independent effects. Moreover, ghrelin may play a role in the management of disorders of gut motility and obesity. Finally, other potential clinical applications of ghrelin include the treatment of patients with diabetes mellitus, infections, rheumatological diseases or GH deficiency and the diagnosis of this hormonal disorder.

Background: The increase in heart rate during exercise is considered to be attributed to sympathetic system activation combined with parasympathetic withdrawal. The prognostic importance of the chronotropic response to exercise and heart rate recovery 1 minute after exercise has already been established. The purpose of this study was to evaluate heart rate recovery as an index of myocardial ischemia, by correlating heart rate recovery with known parameters of myocardial ischemia., Methods and Results: Included in the study were 304 consecutive patients (73% men), aged 34 to 82 years. Patients whose heart rate recovery value or myocardial perfusion imaging could have been influenced by factors other than ischemic disease were excluded from the study. The patients underwent single photon emission computed tomography myocardial perfusion imaging combined with symptom-limited exercise testing with thallium 201 or technetium 99m tetrofosmin. The value for heart rate recovery was defined as the decrease in heart rate from peak exercise to 1 minute after termination of exercise. For semiquantitation of the scintigram, the uptake of the radiotracer was graded on a scale from 0 to 4. Twenty-one beats per minute was defined as the lowest normal value for heart rate recovery. We found 74 patients (24%) with an abnormal value. We also found a significant correlation between heart rate recovery 1 minute after exercise and stress myocardial perfusion score. In addition, there was a statistically significant relationship between heart rate recovery and chronotropic variables. Patients with an abnormal value of heart rate recovery were generally of an older age, were more likely men, had a higher frequency of risk factors for coronary artery disease, were mostly taking cardioactive medications, had lower efficiency during treadmill testing, and had more pathologic findings on the scintigram., Conclusions: Myocardial ischemia, as assessed by myocardial perfusion imaging, is an important correlate of heart rate recovery. There is a significant correlation between chronotropic variables during exercise testing and heart rate recovery 1 minute after exercise. It seems that the heart rate recovery value 1 minute after peak exercise may be considered a reliable index of the severity of myocardial ischemia.