Functional GnRH receptor signaling regulates striatal cholinergic neurons in neonatal but not in adult mice.

Reproduction in mammals is controlled by hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Recent studies from our laboratory established that the basal ganglia of the human brain contain additional large populations of GnRH synthesizing neurons which are absent in adult mice. Such extrahypothalamic GnRH neurons mostly occur in the putamen where they correspond to subsets of the striatal cholinergic interneurons (ChINs) and express GnRHR autoreceptors. In an effort to establish a mouse model for functional studies of striatal GnRH/GnRHR signaling, we carried out electrophysiological experiments on acute brain slices from male transgenic mice. Using PN4-7 neonatal mice, half of striatal ChINs responded with transient hyperpolarization and decreased firing rate to 1.2 µM GnRH, whereas medium spiny projection neurons remained unaffected. GnRH acted on its specific receptor because no response was observed in the presence of the GnRHR antagonist Antide. Addition of the membrane-impermeable G protein-coupled receptor inhibitor GDP-ß-S to the internal electrode solution eliminated the effect of GnRH. Further, GnRH was able to inhibit ChINs in presence of tetrodotoxin which blocked action potential mediated events. Collectively, these data indicated that the receptor underlying the effects of GnRH in neonatal mice is localized within ChINs. GnRH responsiveness of ChINs was transient and entirely disappeared in adult mice. These results raise the possibility to use neonatal transgenic mice as a functional model to investigate the role of GnRH/GnRHR signaling discovered earlier in adult human ChINs.

[A study of the psychosocial characteristics of psychiatric teams in Hungary].

BACKGROUND: In this study, we examined psychiatric teams in a Hungarian sample before the COVID-19 pandemic. The aim of our research is to examine Hungarian psychiatric teams along different workplace psychosocial factors (collaboration management, organization and job, workplace requirements, work-life balance, trust, health and well-being) in order to assess them in terms of hierarchy and competence. Moreover we examine the mental and somatic effects of these factors. METHODS: We conducted a cross-sectional survey of Hungarian mental health care workers (N =79). The main question of the study was how perceived hierarchy and competence boundary violations are associated to psychosocial factors of the COPSOQ-II questionnaire (Copenhagen Psychosocial Questionnaire II) in general, and among employees in different job groups. RESULTS: Based on bootstrapped binary logistic regression performed on the full sample, we found that perceived hierarchy is associated with control, social support of co-workers and stress, while violation of competence boundaries is associated with job recognition, job clarity and fairness. DISCUSSION: Our results show that where mental health care workers experienced less perceived hierarchy within the team, they were more likely to feel that they had control over their work. Furthermore, in hierarchies perceived as superior-subordinate relations, the quality of the relationships within the team seems to be much more important. CONCLUSIONS: This research can be the starting point for a comprehensive study of other psychiatric teams with the aid of a widely used measure, providing an opportunity for comparison with other health teams at an international level.

[The impact of the coronavirus pandemic on the mental health of critical care workers]. / A koronavírus-világjárvány hatása az intenzív ellátásban dolgozók mentális egészségére.

INTRODUCTION: The coronavirus pandemic has focused attention on the importance of critical care and highlighted the shortage of critical care specialists. Due to increasing workloads and high mortality rates, healthcare professionals were exposed to higher levels of physical and psychological stress during the pandemic than before. OBJECTIVE: Our study investigated the effects of the coronavirus outbreak on the emotional, mental and moral stress of intensive care professionals. METHOD: Our workgroup performed paper-based surveys among caregivers in the Department of Anaesthesiology and Intensive Therapy at Semmelweis University. The first survey was conducted at the start of the pandemic in 2020, the second survey was conducted after the third wave in 2021. We applied validated questionnaires (Professional Quality of Life, Demoralization Scale, Perceived Stress Scale, Impact of Event Scale, and Posttraumatic Growth Inventory), collected demographic data and information on lifestyle, recreation, dietary habits, and accepting psychological support. RESULTS: The number and demographic characteristics of the participants in the two studies are different, reflecting the changes in the workforce during the pandemic. Our results revealed no differences between the working and socio-demographic groups before the outbreak, however, one year later, nurses scored significantly higher on all negative psychological scales compared to other groups. Only a minority of the respondents had sought psychological support (9.5-12.7%), although more than a third of respondents reported the need for psychological support. Employees in new work positions showed significantly increased posttraumatic growth (2.91 ± 0.82 vs. 2.20 ± 1.06, p = 0.016). DISCUSSION: These findings demonstrate that nurses are the most strained workgroup during an uncertain and stressful period. The available mental support alone is not enough to help caregivers. CONCLUSION: Further steps are needed to improve the mental health of critical care workers. Orv Hetil. 2023; 164(42): 1646-1655.

[Psychological factors influencing the experience of menstrual pain - the role of pain catastrophizing]. / A menstruációs fájdalom megélését befolyásoló pszichológiai tényezok ­ a fájdalomkatasztrofizálás szerepe.

INTRODUCTION: Research on menstrual pain is lacking in the literature in terms of the number of people affected, the amount of time spent suffering, and the consequences. OBJECTIVE: We examined the role of pain catastrophizing in experiencing the subjective extent and frequency of menstrual pain and its perception as a limitation to daily activities. METHOD: In our study, during personal tests between 2015 and 2018, we collected data from around 1000 healthy women aged 18 to 51 years, predominantly with secondary and higher education, already and still menstruating, mostly living in a large city, mainly in a relationship, perceiving themselves to be in excellent or good health, predominantly not using hormonal contraceptives, mostly having a regular menstrual cycle. We used an open-ended question to measure the extent, frequency, and impact on daily activities of menstrual pain, and used the Pain Catastrophizing Questionnaire. RESULTS: In our own sample, we found that the more the subject "tends" to report pain catastrophizing, the stronger is the menstrual pain she reports, the more often she experiences menstrual pain and says that the pain limits her daily activities. CONCLUSION: The results showed that it is worth examining the personality characteristics among the factors influencing the extent of menstrual pain; the results can be incorporated into diagnostic and therapeutic work. Orv Hetil. 2023; 164(37): 1469-1475.

Development of a versatile LCM-Seq method for spatial transcriptomics of fluorescently tagged cholinergic neuron populations.

Single-cell transcriptomics are powerful tools to define neuronal cell types based on co-expressed gene clusters. Limited RNA input in these technologies necessarily compromises transcriptome coverage and accuracy of differential expression analysis. We propose that bulk RNA-Seq of neuronal pools defined by spatial position offers an alternative strategy to overcome these technical limitations. We report a laser-capture microdissection (LCM)-Seq method which allows deep transcriptome profiling of fluorescently tagged neuron populations isolated with LCM from histological sections of transgenic mice. Mild formaldehyde fixation of ZsGreen marker protein, LCM sampling of ∼300 pooled neurons, followed by RNA isolation, library preparation and RNA-Seq with methods optimized for nanogram amounts of moderately degraded RNA enabled us to detect ∼15,000 different transcripts in fluorescently labeled cholinergic neuron populations. The LCM-Seq approach showed excellent accuracy in quantitative studies, allowing us to detect 2891 transcripts expressed differentially between the spatially defined and clinically relevant cholinergic neuron populations of the dorsal caudate-putamen and medial septum. In summary, the LCM-Seq method we report in this study is a versatile, sensitive, and accurate bulk sequencing approach to study the transcriptome profile and differential gene expression of fluorescently tagged neuronal populations isolated from transgenic mice with high spatial precision.

Assessment of Frontal Hemispherical Lateralization in Plaque Psoriasis and Atopic Dermatitis.

BACKGROUND: Each brain hemisphere plays a specialized role in cognitive and behavioral processes, known as hemispheric lateralization. In chronic skin diseases, such as plaque psoriasis (Pso) and atopic dermatitis (AD), the degree of lateralization between the frontal hemispheres may provide insight into specific connections between skin diseases and the psyche. This study aims to analyze the hemispherical lateralization, neurovegetative responses, and psychometric characteristics of patients with Pso and AD. METHODS: The study included 46 patients with Pso, 56 patients with AD, and 29 healthy control (Ctrl) subjects. The participants underwent frontal electroencephalogram (EEG) measurement, heart rate variability (HRV) assessment, and psychological tests. Statistical analyses were performed using ANOVA, with Bonferroni correction applied for multiple comparisons. RESULTS: This study shows a significant right-lateralized prefrontal activity in both AD patients (p < 0.001) and Pso patients (p = 0.045) compared with Ctrl, with no significant difference between the AD and Pso groups (p = 0.633). AD patients with right-hemispheric dominant prefrontal activation exhibited increased inhibition and avoidance markers, while Pso patients showed elevated sympathetic nervous system activity. CONCLUSION: Psychophysiological and psychometric data suggest a shared prevalence of right-hemispheric dominance in both AD and Pso patient groups. However, the findings indicate distinct psychodermatological mechanisms in AD and Pso.

Dissecting the KNDy hypothesis: KNDy neuron-derived kisspeptins are dispensable for puberty but essential for preserved female fertility and gonadotropin pulsatility.

BACKGROUND: Kiss1 neurons in the hypothalamic arcuate-nucleus (ARC) play key roles in the control of GnRH pulsatility and fertility. A fraction of ARC Kiss1 neurons, termed KNDy, co-express neurokinin B (NKB; encoded by Tac2). Yet, NKB- and Kiss1-only neurons are also found in the ARC, while a second major Kiss1-neuronal population is present in the rostral hypothalamus. The specific contribution of different Kiss1 neuron sub-sets and kisspeptins originating from them to the control of reproduction and eventually other bodily functions remains to be fully determined. METHODS: To tease apart the physiological roles of KNDy-born kisspeptins, conditional ablation of Kiss1 in Tac2-expressing cells was implemented in vivo. To this end, mice with Tac2 cell-specific Kiss1 KO (TaKKO) were generated and subjected to extensive reproductive and metabolic characterization. RESULTS: TaKKO mice displayed reduced ARC kisspeptin content and Kiss1 expression, with greater suppression in females, which was detectable at infantile-pubertal age. In contrast, Tac2/NKB levels were fully preserved. Despite the drop of ARC Kiss1/kisspeptin, pubertal timing was normal in TaKKO mice of both sexes. However, young-adult TaKKO females displayed disturbed LH pulsatility and sex steroid levels, with suppressed basal LH and pre-ovulatory LH surges, early-onset subfertility and premature ovarian insufficiency. Conversely, testicular histology and fertility were grossly conserved in TaKKO males. Ablation of Kiss1 in Tac2-cells led also to sex-dependent alterations in body composition, glucose homeostasis, especially in males, and locomotor activity, specifically in females. CONCLUSIONS: Our data document that KNDy-born kisspeptins are dispensable/compensable for puberty in both sexes, but required for maintenance of female gonadotropin pulsatility and fertility, as well as for adult metabolic homeostasis. SIGNIFICANCE STATEMENT: Neurons in the hypothalamic arcuate nucleus (ARC) co-expressing kisspeptins and NKB, named KNDy, have been recently suggested to play a key role in pulsatile secretion of gonadotropins, and hence reproduction. However, the relative contribution of this Kiss1 neuronal-subset, vs. ARC Kiss1-only and NKB-only neurons, as well as other Kiss1 neuronal populations, has not been assessed in physiological settings. We report here findings in a novel mouse-model with elimination of KNDy-born kisspeptins, without altering other kisspeptin compartments. Our data highlights the heterogeneity of ARC Kiss1 populations and document that, while dispensable/compensable for puberty, KNDy-born kisspeptins are required for proper gonadotropin pulsatility and fertility, specifically in females, and adult metabolic homeostasis. Characterization of this functional diversity is especially relevant, considering the potential of kisspeptin-based therapies for management of human reproductive disorders.

The impact of the first wave of COVID-19 on students' attainment, analysed by IRT modelling method.

Universities around the world were closed for several months to slow down the spread of the COVID-19 pandemic. During this crisis, a tremendous amount of effort was made to use online education to support the teaching and learning process. The COVID-19 pandemic gave us a profound insight into how online education can radically affect students and how students adapt to new challenges. The question is how switching to online education affected dropout? This study shows the results of a research project clarifying the impact of the transition to online courses on dropouts. The data analysed are from a large public university in Europe where online education was introduced in March 2020. This study compares the academic progress of students newly enroled in 2018 and 2019 using IRT modelling. The results show that (1) this period did not contribute significantly to the increase in dropout, and we managed to retain our students.(2) Subjects became more achievable during online education, and students with less ability were also able to pass their exams. (3) Students who participated in online education reported lower average grade points than those who participated in on-campus education. Consequently, on-campus students could win better scholarships because of better grades than students who participated in online education. Analysing students' results could help (1) resolve management issues regarding scholarship problems and (2) administrators develop programmes to increase retention in online education.

The Effectiveness of Psychological Interventions for Rheumatoid Arthritis (RA): A Systematic Review and Meta-Analysis.

Rheumatoid arthritis (RA) is a long-term disorder that significantly impairs somatic, emotional, and psychological functioning. The objective of this review is to identify, appraise, and synthesize the effects of psychological interventions (e.g., cognitive behavioral therapy (CBT), emotional disclosure (ED), group therapy (GT), mindfulness (M), patient education (PE), and relaxation (R)) on biopsychosocial outcomes in the treatment of rheumatoid arthritis (RA). A systematic search of all relevant existing randomized clinical trials (RCTs) was conducted using the following online bibliographic databases: JSTOR, PubMed, PsycNET, and The Cochrane Library. Reference lists were searched for additional reports. The Cochrane Risk of Bias tool (RoB 2.0) was used to assess the risk of bias in the included studies. After the selection process, 57 articles were included and 392 were excluded. Three separate meta-analyses were conducted involving psychological interventions as the main variables, showing: (1) significant positive medium effect sizes for average values (Hedges-g = 0.399, Z = 0.399, p = 0.009); (2) significant positive large effect sizes for maximum values (Hedges-g = 0.856, Z = 4.223, p < 0.001); and (3) non-significant results for minimum values (Hedges-g = -0.047, Z = -0.335, p = 0.738). These results demonstrate that, when grouped, psychological interventions are, on average, moderately effective in treating RA. Overall, this review shows consistent, supportive evidence that psychological interventions can significantly contribute to the standard medical care of RA patients. However, more high-quality, large-sample RCTs still need to confirm these findings.

Oncological Screening of Kidney Tumors After Renal Transplantation.

BACKGROUND: Among renal transplant recipients, renal cell carcinoma in the native kidneys represents the most common solid tumor. At the Department of Surgery, Transplantation and Gastroenterology of Semmelweis University annual control abdominal ultrasound examination is recommended for transplant patients. Our goal was to evaluate the effectiveness of the ultrasound screening program at our institute and to learn about the characteristics of shrunken kidney tumors. METHODS: Retrospectively, we processed the results of abdominal and pelvic ultrasound examinations of 1687 kidney transplant patients, which were performed at our institute between January 1, 2012 and December 31, 2016. RESULTS: A total of 26 tumors were detected during the abovementioned period of time, of which 18 were renal cancers. Renal cancer was significantly (P = 0.029) more common in men. Seventeen renal cancers were classified as stage I and one as stage IV disease. The mean time of dialysis was 37.73 ± 24.37 months. The mean time between kidney transplantation and tumor recognition was 7.9 ± 6.29 years. The 5-year survival was 66%; however, it should be noted that only 1 patient lost his life due to his tumor disease. The mean time between the last 2 ultrasound examinations was 27.8 ± 23.89 months. Only 57% of tumors were detected by screening. No significant differences in tumor size, stage, and survival could be detected between screened and nonscreened renal cancer patients. CONCLUSIONS: Ultrasound examination at least every 2 years is an effective tool for the early detection of renal cell carcinoma of the shrunken kidneys.

Estrogen differentially regulates transcriptional landscapes of preoptic and arcuate kisspeptin neuron populations.

Kisspeptin neurons residing in the rostral periventricular area of the third ventricle (KPRP3V) and the arcuate nucleus (KPARC) mediate positive and negative estrogen feedback, respectively. Here, we aim to compare transcriptional responses of KPRP3V and KPARC neurons to estrogen. Transgenic mice were ovariectomized and supplemented with either 17ß-estradiol (E2) or vehicle. Fluorescently tagged KPRP3V neurons collected by laser-capture microdissection were subjected to RNA-seq. Bioinformatics identified 222 E2-dependent genes. Four genes encoding neuropeptide precursors (Nmb, Kiss1, Nts, Penk) were robustly, and Cartpt was subsignificantly upregulated, suggesting putative contribution of multiple neuropeptides to estrogen feedback mechanisms. Using overrepresentation analysis, the most affected KEGG pathways were neuroactive ligand-receptor interaction and dopaminergic synapse. Next, we re-analyzed our previously obtained KPARC neuron RNA-seq data from the same animals using identical bioinformatic criteria. The identified 1583 E2-induced changes included suppression of many neuropeptide precursors, granins, protein processing enzymes, and other genes related to the secretory pathway. In addition to distinct regulatory responses, KPRP3V and KPARC neurons exhibited sixty-two common changes in genes encoding three hormone receptors (Ghsr, Pgr, Npr2), GAD-65 (Gad2), calmodulin and its regulator (Calm1, Pcp4), among others. Thirty-four oppositely regulated genes (Kiss1, Vgf, Chrna7, Tmem35a) were also identified. The strikingly different transcriptional responses in the two neuron populations prompted us to explore the transcriptional mechanism further. We identified ten E2-dependent transcription factors in KPRP3V and seventy in KPARC neurons. While none of the ten transcription factors interacted with estrogen receptor-α, eight of the seventy did. We propose that an intricate, multi-layered transcriptional mechanism exists in KPARC neurons and a less complex one in KPRP3V neurons. These results shed new light on the complexity of estrogen-dependent regulatory mechanisms acting in the two functionally distinct kisspeptin neuron populations and implicate additional neuropeptides and mechanisms in estrogen feedback.

Transcriptome profiling of kisspeptin neurons from the mouse arcuate nucleus reveals new mechanisms in estrogenic control of fertility.

Kisspeptin neurons in the mediobasal hypothalamus (MBH) are critical targets of ovarian estrogen feedback regulating mammalian fertility. To reveal molecular mechanisms underlying this signaling, we thoroughly characterized the estrogen-regulated transcriptome of kisspeptin cells from ovariectomized transgenic mice substituted with 17ß-estradiol or vehicle. MBH kisspeptin neurons were harvested using laser-capture microdissection, pooled, and subjected to RNA sequencing. Estrogen treatment significantly (p.adj. < 0.05) up-regulated 1,190 and down-regulated 1,139 transcripts, including transcription factors, neuropeptides, ribosomal and mitochondrial proteins, ion channels, transporters, receptors, and regulatory RNAs. Reduced expression of the excitatory serotonin receptor-4 transcript (Htr4) diminished kisspeptin neuron responsiveness to serotonergic stimulation. Many estrogen-regulated transcripts have been implicated in puberty/fertility disorders. Patients (n = 337) with congenital hypogonadotropic hypogonadism (CHH) showed enrichment of rare variants in putative CHH-candidate genes (e.g., LRP1B, CACNA1G, FNDC3A). Comprehensive characterization of the estrogen-dependent kisspeptin neuron transcriptome sheds light on the molecular mechanisms of ovary-brain communication and informs genetic research on human fertility disorders.

Exploring Coping Strategies of Different Generations of Students Starting University.

Introduction: Coping strategies and adaptation skills are key features in successfully adjusting to university challenges. Coping skills are an essential part of the Psychological immune system, which leads to successful adaptation. Due to COVID-19 most universities have changed their face-to-face teaching for online education. Nevertheless, there is little concrete empirical evidence on how this generation of students with the ongoing impacts of disruptive changes can cope with it. Colleges and universities need to make changes in order to retain this new generation of students. Our aim was to explore the characteristics and changes in coping skills of university students from three different age groups. Method: Psychological coping skills were measured by the Psychological Immune Competence Inventory (PICI). Differences were detected between generations. Group comparisons (pre-2004, pre-Covid, and post-Covid) groups were compared) using PICI subscales using independent sample analysis of variance. The sample consisted of 4,731 university students, 2,768 (58.5%) were men and 1,730 (36.56%) were women. Results: Students from 2004 showed significantly higher scores in the Self-regulation subsystem scale compared to students in the pre-Covid and post-Covid groups. Self-regulation subsystem: F(2, 2,569.607) = 444.375, p < 0.001, η2 = 0.27: small effect, ω2 = 0.27; Resilience: F(2, 2,372.117) = 1171.855, p < 0.001, η2 = 0.14: small effect, ω2 = 0.14. Based on the results, the explained variance ratio was at least 10% based on self-regulation and resilience. Conclusions: Psychological immune capacity of students seems to decrease through the years. Nonetheless, interventions may have a further facilitating role in the maintenance and development of psychological immunity during college years.

The human hypothalamic kisspeptin system: Functional neuroanatomy and clinical perspectives.

In mammals, kisspeptin neurons are the key components of the hypothalamic neuronal networks that regulate the onset of puberty, account for the pulsatile secretion of gonadotropin-releasing hormone (GnRH) and mediate negative and positive estrogen feedback signals to GnRH neurons. Being directly connected anatomically and functionally to the hypophysiotropic GnRH system, the major kisspeptin cell groups of the preoptic area/rostral hypothalamus and the arcuate (or infundibular) nucleus, respectively, are ideally positioned to serve as key nodes which integrate various types of environmental, endocrine, and metabolic signals that can influence fertility. This chapter provides an overview of the current state of knowledge on the anatomy, functions, and plasticity of brain kisspeptin systems based on the wide literature available from different laboratory and domestic species. Then, the species-specific features of human hypothalamic kisspeptin neurons are described, covering their topography, morphology, unique neuropeptide content, plasticity, and connectivity to hypophysiotropic GnRH neurons. Some newly emerging roles of central kisspeptin signaling in behavior and finally, clinical perspectives, are discussed.

Statistical analysis of the Hungarian COVID-19 victims.

With the wide spread of Coronavirus, most people who infected with the COVID-19, will recover without requiring special treatment. Whereas, elders and those with underlying medical problems are more likely to have serious illnesses, even be threatened with death. Many more disciplines try to find solutions and drive master plan to this global trouble. Consequently, by taking one particular population, Hungary, this study aims to explore a pattern of COVID-19 victims, who suffered from some underlying conditions. Age, gender, and underlying medical problems form the structure of the clustering. K-Means and two step clustering methods were applied for age-based and age-independent analysis. Grouping of the deaths in the form of two different scenarios may highlight some concepts of this deadly disease for public health professionals. Our result for clustering can forecast similar cases which are assigned to any cluster that it will be a serious cautious for the population.

ADHD symptomatology of children with congenital heart disease 10 years after cardiac surgery: the role of age at operation.

BACKGROUND: The aim of the present study was to investigate the differences in ADHD symptomatology between healthy controls and children who underwent cardiac surgery at different ages. METHODS: Altogether, 133 children (54 patients with congenital heart disease undergoing first cardiac surgery under 3 years of age, 26 operated at the age of 3 or later, and 53 healthy controls) were examined. Patients completed the Youth Self Report (YSR), while their parents completed the Child Behaviour Checklist (CBCL) and the ADHD Rating Scale-IV. RESULTS: Children receiving surgery for the first time under the age of 3 years were more likely diagnosed with cyanotic type malformation and have undergone to a greater number of operations. However, ADHD symptoms of those treated surgically at or above 3 years of age were more severe than that of the control group or those who were treated surgically at a younger age. The control group and those treated surgically below the age of three did not differ across any of the ADHD symptom severity indicators. CONCLUSIONS: The age at the time of cardiac surgery might be associated with later ADHD symptom severity - with lower age at operation associated with better outcomes. Further, adequately powered studies are needed to confirm these exploratory findings and investigate the moderators of this relationship.

The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia.

Human reproduction is controlled by ~2000 hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Here, we report the discovery and characterization of additional ~150,000-200,000 GnRH-synthesizing cells in the human basal ganglia and basal forebrain. Nearly all extrahypothalamic GnRH neurons expressed the cholinergic marker enzyme choline acetyltransferase. Similarly, hypothalamic GnRH neurons were also cholinergic both in embryonic and adult human brains. Whole-transcriptome analysis of cholinergic interneurons and medium spiny projection neurons laser-microdissected from the human putamen showed selective expression of GNRH1 and GNRHR1 autoreceptors in the cholinergic cell population and uncovered the detailed transcriptome profile and molecular connectome of these two cell types. Higher-order non-reproductive functions regulated by GnRH under physiological conditions in the human basal ganglia and basal forebrain require clarification. The role and changes of GnRH/GnRHR1 signaling in neurodegenerative disorders affecting cholinergic neurocircuitries, including Parkinson's and Alzheimer's diseases, need to be explored.

Characterization of Kisspeptin Neurons in the Human Rostral Hypothalamus.

BACKGROUND: Kisspeptin (KP) neurons in the rostral periventricular region of the 3rd ventricle (RP3V) of female rodents mediate positive estrogen feedback to gonadotropin-releasing hormone neurons and, thus, play a fundamental role in the mid-cycle luteinizing hormone (LH) surge. The RP3V is sexually dimorphic, and male rodents with lower KP cell numbers are unable to mount estrogen-induced LH surges. OBJECTIVE: To find and characterize the homologous KP neurons in the human brain, we studied formalin-fixed post-mortem hypothalami. METHODS: Immunohistochemical techniques were used. RESULTS: The distribution of KP neurons in the rostral hypothalamus overlapped with distinct subdivisions of the paraventricular nucleus. The cell numbers decreased after menopause, indicating that estrogens positively regulate KP gene expression in the rostral hypothalamus in humans, similarly to several other species. Young adult women and men had similar cell numbers, as opposed to rodents reported to have more KP neurons in the RP3V of females. Human KP neurons differed from the homologous rodent cells as well, in that they were devoid of enkephalins, galanin and tyrosine hydroxylase. Further, they did not contain known KP neuron markers of the human infundibular nucleus, neurokinin B, substance P and cocaine- and amphetamine-regulated transcript, while they received afferent input from these KP neurons. CONCLUSIONS: The identification and positive estrogenic regulation of KP neurons in the human rostral hypothalamus challenge the long-held view that positive estrogen feedback may be restricted to the mediobasal part of the hypothalamus in primates and point to the need of further anatomical, molecular and functional studies of rostral hypothalamic KP neurons.

Our initial experiences with mpMRI-ultrasound fusion-guided prostate biopsy / Kezdeti tapasztalataink az mpMR fúziós ultrahangvezérelt prosztatabiopsziával

Introduction: The past decade has seen some major changes in the diagnostics of prostate cancer. Progress in MR imaging has allowed us to better visualise prostate cancer and thus perform targeted biopsies of tumour suspect lesions. mpMRI-ultrasound fusion-guided prostate biopsy is a precise and cost-effective method to diagnose prostate cancer. Objective: The purpose of this study was to summarise our results in mpMRI-ultrasound fusion biopsy between 2017 and 2019 and compare them with the findings in the current literature. Method: Between 2017 and 2019, fully 40, mpMRI-ultrasound fusion biopsies were performed transperineally using the BioJet fusion system at Semmelweis University Urology Clinic. The MRI evaluations were done in line with the PI-RADS v2 guidelines. It was analysed whether the PI-RADS score, the location of the tumour, lesion size, the signs of extraprostatic extension, PSA/PSAD density and prostate volume have an influence on the outcome of mpMRI-ultrasound fusion biopsy. Results: Prostate cancer was diagnosed in 80% of the cases during targeted biopsies. The detection rate was 91%, 85%, and 20% for PI-RADS 5, 4 and 3 lesions, respectively. The detection rate was significantly higher for lesions located at the peripheral zone compared to the ones in the transitional zone (khi2(1) = 6.555, p = 0.010, Fisher-exact p = 0.017, V = 0.355). Signs of extraprostatic extension and higher PSAD correlated with better detection rate (khi2(1)= 7.704, p = 0.006, Fisher-exact p = 0.004, V = 0.355; and 0.47 ± 0.50 ng/ml2 vs. 0.18 ± 0.17 ng/ml2; Z = 3.447, p<0.001, respectively). The size of the lesions did not influence the outcome. The analysis showed a significant correlation between large prostate volumes and negative biopsies (50.9 ± 18.8 ml vs. 119.6 ± 91.6 ml; Z= ­3.505, p<0.001). Conclusions: The detection rate of prostate cancer with targeted biopsies was higher than the data found in the international literature. The PI-RADS score, the location of the tumour, MRI signs of extraprostatic extension, PSAD and prostate volume had an influence on the detection rate. Our findings may promote a better selection of the best candidates for targeted biopsies in the future.

Kisspeptin Neurons in the Infundibular Nucleus of Ovariectomized Cats and Dogs Exhibit Unique Anatomical and Neurochemical Characteristics.

Neurons co-synthesizing kisspeptin (KP), neurokinin B (NKB), and dynorphin ("KNDy neurons") in the hypothalamic arcuate/infundibular nucleus (INF) form a crucial component of the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) "pulse generator." The goal of our study was to characterize KP neuron distribution, neuropeptide phenotype and connectivity to GnRH cells in ovariectomized (OVX) dogs and cats with immunohistochemistry on formalin-fixed hypothalamic tissue sections. In both species, KP and NKB neurons occurred in the INF and the two cell populations overlapped substantially. Dynorphin was detected in large subsets of canine KP (56%) and NKB (37%) cells and feline KP (64%) and NKB (57%) cells; triple-labeled ("KNDy") somata formed ∼25% of all immunolabeled neurons. Substance P (SP) was present in 20% of KP and 29% of NKB neurons in OVX cats but not dogs, although 26% of KP and 24% of NKB neurons in a gonadally intact male dog also contained SP signal. Only in cats, cocaine- and amphetamine regulated transcript was also colocalized with KP (23%) and NKB (7%). In contrast with reports from mice, KP neurons did not express galanin in either carnivore. KP neurons innervated virtually all GnRH neurons in both species. Results of this anatomical study on OVX animals reveal species-specific features of canine and feline mediobasal hypothalamic KP neurons. Anatomical and neurochemical similarities to and differences from the homologous KP cells of more extensively studied rodent, domestic and primate species will enhance our understanding of obligate and facultative players in the molecular mechanisms underlying pulsatile GnRH/LH secretion.