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1.
J Am Soc Cytopathol ; 13(4): 309-318, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38702208

RESUMEN

INTRODUCTION: Effective feedback on cytology performance relies on navigating complex laboratory information system data, which is prone to errors and lacks flexibility. As a comprehensive solution, we used the Python programming language to create a dashboard application for screening and diagnostic quality metrics. MATERIALS AND METHODS: Data from the 5-year period (2018-2022) were accessed. Versatile open-source Python libraries (user developed program code packages) were used from the first step of LIS data cleaning through the creation of the application. To evaluate performance, we selected 3 gynecologic metrics: the ASC/LSIL ratio, the ASC-US/ASC-H ratio, and the proportion of cytologic abnormalities in comparison to the total number of cases (abnormal rate). We also evaluated the referral rate of cytologists/cytotechnologists (CTs) and the ratio of thyroid AUS interpretations by cytopathologists (CPs). These were formed into colored graphs that showcase individual results in established, color-coded laboratory "goal," "borderline," and "attention" zones based on published reference benchmarks. A representation of the results distribution for the entire laboratory was also developed. RESULTS: We successfully created a web-based test application that presents interactive dashboards with different interfaces for the CT, CP, and laboratory management (https://drkvcsstvn-dashboards.hf.space/app). The user can choose to view the desired quality metric, year, and the anonymized CT or CP, with an additional automatically generated written report of results. CONCLUSIONS: Python programming proved to be an effective toolkit to ensure high-level data processing in a modular and reproducible way to create a personalized, laboratory specific cytology dashboard.


Asunto(s)
Lenguajes de Programación , Garantía de la Calidad de Atención de Salud , Humanos , Femenino , Citodiagnóstico/métodos , Citodiagnóstico/normas , Programas Informáticos , Citología
2.
Front Endocrinol (Lausanne) ; 15: 1353151, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38348415

RESUMEN

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.


Asunto(s)
Hormona Liberadora de Gonadotropina , Receptores LHRH , Animales , Masculino , Ratones , Neuronas Colinérgicas , Hormona Liberadora de Gonadotropina/farmacología , Mamíferos , Ratones Transgénicos , Transducción de Señal
3.
Metabolism ; 144: 155556, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37121307

RESUMEN

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.


Asunto(s)
Gonadotropinas , Kisspeptinas , Masculino , Femenino , Ratones , Humanos , Animales , Kisspeptinas/genética , Neuronas/metabolismo , Pubertad , Hormona Liberadora de Gonadotropina/metabolismo , Núcleo Arqueado del Hipotálamo/metabolismo , Fertilidad
4.
Transplant Proc ; 54(9): 2589-2592, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36396469

RESUMEN

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.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Trasplante de Riñón , Masculino , Humanos , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/etiología , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Estudios Retrospectivos , Diálisis Renal , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/etiología , Riñón
5.
Front Endocrinol (Lausanne) ; 13: 960769, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36093104

RESUMEN

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.


Asunto(s)
Núcleo Arqueado del Hipotálamo , Kisspeptinas , Animales , Núcleo Arqueado del Hipotálamo/metabolismo , Estrógenos/metabolismo , Estrógenos/farmacología , Kisspeptinas/genética , Kisspeptinas/metabolismo , Ratones , Ratones Transgénicos , Neuronas/metabolismo , Factores de Transcripción/metabolismo
6.
Proc Natl Acad Sci U S A ; 119(27): e2113749119, 2022 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-35763574

RESUMEN

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.


Asunto(s)
Núcleo Arqueado del Hipotálamo , Estrógenos , Fertilidad , Kisspeptinas , Neuronas , Ovario , Animales , Núcleo Arqueado del Hipotálamo/metabolismo , Estrógenos/metabolismo , Femenino , Fertilidad/genética , Perfilación de la Expresión Génica , Humanos , Hipogonadismo/congénito , Hipogonadismo/genética , Kisspeptinas/genética , Kisspeptinas/metabolismo , Ratones , Ratones Transgénicos , Neuronas/metabolismo , Ovario/metabolismo
7.
Handb Clin Neurol ; 180: 275-296, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34225935

RESUMEN

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.


Asunto(s)
Kisspeptinas , Neuroanatomía , Animales , Núcleo Arqueado del Hipotálamo/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Humanos , Hipotálamo/metabolismo , Kisspeptinas/metabolismo
8.
J Med Virol ; 93(12): 6660-6670, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34324217

RESUMEN

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.


Asunto(s)
COVID-19/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Asma/complicaciones , COVID-19/etiología , Complicaciones de la Diabetes/epidemiología , Femenino , Humanos , Hungría/epidemiología , Enfermedades Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Obesidad/complicaciones , Factores de Riesgo , Esquizofrenia/complicaciones , Factores Sexuales , Adulto Joven
9.
BMC Psychiatry ; 21(1): 316, 2021 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-34167512

RESUMEN

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.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Procedimientos Quirúrgicos Cardíacos , Cardiopatías Congénitas , Adolescente , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Niño , Preescolar , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/cirugía , Humanos , Padres
10.
Elife ; 102021 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-34128468

RESUMEN

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.


Asunto(s)
Ganglios Basales , Hormona Liberadora de Gonadotropina/metabolismo , Neuronas , Adulto , Prosencéfalo Basal/citología , Ganglios Basales/citología , Ganglios Basales/metabolismo , Ganglios Basales/fisiología , Células Cultivadas , Colina O-Acetiltransferasa , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronas/citología , Neuronas/metabolismo , Neuronas/fisiología , Putamen/citología , Transcriptoma
11.
Neuroendocrinology ; 111(3): 249-262, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32299085

RESUMEN

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.


Asunto(s)
Estrógenos/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Kisspeptinas/metabolismo , Menopausia/metabolismo , Neuronas/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Área Preóptica/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Autopsia , Femenino , Humanos , Inmunohistoquímica , Masculino , Microscopía Confocal , Persona de Mediana Edad , Núcleo Hipotalámico Paraventricular/citología , Área Preóptica/citología , Adulto Joven
12.
Orv Hetil ; 161(52): 2188-2194, 2020 12 27.
Artículo en Húngaro | MEDLINE | ID: mdl-33361504

RESUMEN

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.


Asunto(s)
Biopsia Guiada por Imagen/métodos , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Neoplasias de la Próstata/diagnóstico , Ultrasonografía Intervencional/métodos , Humanos , Masculino
13.
Neuroendocrinology ; 109(3): 230-241, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30612127

RESUMEN

The human infundibular nucleus (corresponding to the rodent arcuate nucleus) serves as an important integration center for neuronal signals and hormones released by peripheral endocrine organs. Kisspeptin (KP)-producing neurons of this anatomical site, many of which also synthesize neurokinin B (NKB), are critically involved in sex hormone signaling to gonadotropin-releasing hormone (GnRH) neurons. In recent years, the basic topography, morphology, neuropeptide content, and connectivity of human KP neurons have been investigated with in situ hybridization and immunohistochemistry on postmortem tissues. These studies revealed that human KP neurons differ neurochemically from their rodent counterparts and show robust aging-related plasticity. Earlier immunohistochemical experiments also provided evidence for temporal changes in the hypothalamus of aging men whose NKB and KP neurons undergo hypertrophy, increase in number, exhibit increased neuropeptide mRNA expression and immunoreactivity and give rise to higher numbers of immunoreactive fibers and afferent contacts onto GnRH neurons. Increasing percentages of KP-expressing NKB perikarya, NKB axons, and NKB inputs to GnRH neurons raise the intriguing possibility that a significant subset of NKB neurons begins to cosynthesize KP as aging advances. Although use of postmortem tissues is technically challenging, recently available single-cell anatomical and molecular approaches discussed in this review provide promising new tools to investigate the aging-related anatomical and functional plasticity of the human KP neuronal system.


Asunto(s)
Envejecimiento/metabolismo , Encéfalo/citología , Encéfalo/metabolismo , Kisspeptinas/metabolismo , Neuronas/citología , Neuronas/metabolismo , Envejecimiento/patología , Encéfalo/patología , Humanos , Neuronas/patología
14.
Orv Hetil ; 159(35): 1441-1449, 2018 Sep.
Artículo en Húngaro | MEDLINE | ID: mdl-30146907

RESUMEN

INTRODUCTION: The Professional Quality of Life Scale, measuring the quality of professional life, has been developed to examine the positive and negative changes in the work of those who have undergone extremely stressful experiences. The quality of life of the personnel of palliative-hospice teams may be influenced physically as well as emotionally by their every-day experiences of suffering, death, dying and the patients' traumas. AIM: The aim of the study was the examination of the psychometric features and factor structure of the Hungarian version of the Professional Quality of Life Scale questionnaire, which can measure compassion fatigue and satisfaction, secondary traumatisation and burnout. Our long-term objective is the development of formative and intervention strategies for hospice workers in order to increase their satisfaction, physical and mental well-being and their willingness to work in hospice. METHOD: The cross-sectional, questionnaire study was made with hospice workers. The questionnaires were available in an anonym, printed form. We used the Hungarian versions of the Shortened Maastricht Vital Exhaustion Questionnaire and of the Shortened Beck Depression Scale, of the CES-D Depression Scale and of the Shortened WHO General Well-Being Scale to validate. STATISTICAL ANALYSIS: IBM SPSS 23.0© software was used for the analysis. To explore the factor structure of the measurement scale, explorative factor analysis was made (analysis of the main component, Varimax rotation); subsequently, 4 scales were prepared the Cronbach-alpha values of which were suitable for further examination. RESULTS: 188 questionnaires were sent back (female 86.2%, male 13.8%); the majority work as nurses and in home hospice care (94 people). The inner consistency of the created 4 scales is acceptable according to the Cronbach-alpha values. The inner consistency of the questions regarding burnout is low. The correlation of our measurement scales with the standardised scales for outer validity has sufficient strength and direction. CONCLUSIONS: Our questionnaire can measure the phenomena under examination according to the expected values, with suitable consistency on the basis of the inner and outer indicators. Orv Hetil. 2018; 159(35): 1441-1449.


Asunto(s)
Agotamiento Profesional/psicología , Cuidados Paliativos al Final de la Vida/psicología , Calidad de Vida/psicología , Encuestas y Cuestionarios/normas , Adaptación Psicológica , Adulto , Agotamiento Profesional/diagnóstico , Femenino , Humanos , Hungría , Masculino , Persona de Mediana Edad , Cuidados Paliativos/psicología , Satisfacción Personal , Psicometría , Carga de Trabajo/psicología
15.
Brain Struct Funct ; 223(5): 2143-2156, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29380121

RESUMEN

Kisspeptin (KP) synthesizing neurons of the hypothalamic infundibular region are critically involved in the central regulation of fertility; these cells regulate pulsatile gonadotropin-releasing hormone (GnRH) secretion and mediate sex steroid feedback signals to GnRH neurons. Fine structural analysis of the human KP system is complicated by the use of post mortem tissues. To gain better insight into the neuroanatomy of the somato-dendritic cellular compartment, we introduced the diolistic labeling of immunohistochemically identified KP neurons using a gene gun loaded with the lipophilic dye, DiI. Confocal microscopic studies of primary dendrites in 100-µm-thick tissue sections established that 79.3% of KP cells were bipolar, 14.1% were tripolar, and 6.6% were unipolar. Primary dendrites branched sparsely, contained numerous appendages (9.1 ± 1.1 spines/100 µm dendrite), and received rich innervation from GABAergic, glutamatergic, and KP-containing terminals. KP neuron synaptology was analyzed with immunoelectron microscopy on perfusion-fixed specimens. KP axons established frequent contacts and classical synapses on unlabeled, and on KP-immunoreactive somata, dendrites, and spines. Synapses were asymmetric and the presynaptic structures contained round and regular synaptic vesicles, in addition to dense-core granules. Although immunofluorescent studies failed to detect vesicular glutamate transporter isoforms in KP axons, ultrastructural characteristics of synaptic terminals suggested use of glutamatergic, in addition to peptidergic, neurotransmission. In summary, immunofluorescent and DiI labeling of KP neurons in thick hypothalamic sections and immunoelectron microscopic studies of KP-immunoreactive neurons in brains perfusion-fixed shortly post mortem allowed us to identify previously unexplored fine structural features of KP neurons in the mediobasal hypothalamus of humans.


Asunto(s)
Hipotálamo/citología , Kisspeptinas/metabolismo , Neuronas/citología , Neuronas/metabolismo , Anciano , Anciano de 80 o más Años , Autopsia , Axones/metabolismo , Axones/ultraestructura , Carbocianinas/metabolismo , Cuerpo Celular/ultraestructura , Dendritas/metabolismo , Dendritas/ultraestructura , Ácido Glutámico/metabolismo , Humanos , Imagenología Tridimensional , Kisspeptinas/ultraestructura , Lisina/análogos & derivados , Lisina/metabolismo , Masculino , Microscopía Confocal , Microscopía Inmunoelectrónica , Persona de Mediana Edad , Red Nerviosa/metabolismo , Red Nerviosa/ultraestructura , Sinapsis/metabolismo , Sinapsis/ultraestructura , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo , Proteína 2 de Transporte Vesicular de Glutamato/ultraestructura , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores/metabolismo , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores/ultraestructura , Ácido gamma-Aminobutírico/metabolismo
16.
Eur J Gastroenterol Hepatol ; 30(1): 27-32, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29049126

RESUMEN

OBJECTIVES: Direct-acting antiviral agents have revolutionized hepatitis C therapy, and are also found to be effective in the liver transplant setting. The extent of liver fibrosis influences patient management and is used to monitor therapeutic effects. Shear-wave elastography (SWE) is a relatively new imaging-based method that has not yet been studied extensively in liver transplant patients. Our aim was to study the effect of direct-acting antivirals in heaptitis C recurrence on liver stiffness determined by SWE. PATIENTS AND METHODS: A total of 23 liver transplant patients with hepatitis C recurrence were enrolled in this prospective study. The patients underwent 24 weeks of ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin combination therapy. Elastographic examinations, serological tests and laboratory tests were performed, and serum biomarkers of liver fibrosis were calculated the day before treatment (baseline) and at the end of the treatment. RESULTS: All our patients became hepatitis C virus RNA negative by the end of the treatment. Median liver stiffness values decreased significantly after treatment compared with baseline (8.72±3.77 vs. 7.19±2.4 kPa; P<0.001). Among the studied laboratory values, a significant decrease was observed in the levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase, whereas international normalized ratio levels increased. Serum biomarkers, namely aspartate aminotransferase-to-platelet ratio index and Fibrosis-4, decreased significantly after treatment compared with baseline. CONCLUSION: In the present study, SWE was succesfully used to monitor the beneficial therapeutic effects of direct-acting antivirals in hepatitis C recurrence following liver transplantation. We believe that SWE is a useful noninvasive diagnostic tool in the follow-up of hepatitis C treatment in liver transplant patients.


Asunto(s)
Antivirales/uso terapéutico , Diagnóstico por Imagen de Elasticidad , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Trasplante de Hígado/efectos adversos , Activación Viral/efectos de los fármacos , Anciano , Antivirales/efectos adversos , Pruebas Enzimáticas Clínicas , Femenino , Hepacivirus/genética , Hepacivirus/patogenicidad , Hepatitis C Crónica/sangre , Hepatitis C Crónica/diagnóstico por imagen , Hepatitis C Crónica/virología , Humanos , Relación Normalizada Internacional , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , ARN Viral/sangre , ARN Viral/genética , Recurrencia , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Carga Viral
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