Social withdrawal and anxiety-like behavior have an impact on zebrafish adult neurogenesis.

Introduction: Accumulating evidence highlights the key role of adult neurogenesis events in environmental challenges, cognitive functions and mood regulation. Abnormal hippocampal neurogenesis has been implicated in anxiety-like behaviors and social impairments, but the possible mechanisms remain elusive. Methods: The present study questioned the contribution of altered excitation/inhibition as well as excessive neuroinflammation in regulating the neurogenic processes within the Social Decision-Making (SDM) network, using an adult zebrafish model displaying NMDA receptor hypofunction after sub-chronic MK-801 administration. For this, the alterations in cell proliferation and newborn cell densities were evaluated using quantitative 5-Bromo-2'-Deoxyuridine (BrdU) methodology. Results: In short-term survival experiments. MK-801-treated zebrafish displayed decreased cell proliferation pattern within distinct neurogenic zones of telencephalic and preoptic SDM nodes, in parallel to the social withdrawal and anxiety-like comorbidity. BrdU+ cells co-expressed the pro-inflammatory marker IL-1ß solely in MK-801-treated zebrafish, indicating a role of inflammation. Following the cessation of drug treatment, significant increases in the BrdU+ cell densities were accompanied by the normalization of the social and anxiety-like phenotype. Importantly, most labeled cells in neurogenic zones showed a radial glial phenotype while a population of newborn cells expressed the early neuronal marker TOAD or mGLuR5, the latter suggesting the possible involvement of metabotropic glutamate receptor 5 in neurogenic events. Discussion: Overall, our results indicate the role of radial glial cell proliferation in the overlapping pathologies of anxiety and social disorders, observed in many neuropsychiatric disorders and possibly represent potential novel targets for amelioration of these symptoms.

Altered GABAergic, glutamatergic and endocannabinoid signaling is accompanied by neuroinflammatory response in a zebrafish model of social withdrawal behavior.

Introduction: Deficits in social communication are in the core of clinical symptoms characterizing many neuropsychiatric disorders such as schizophrenia and autism spectrum disorder. The occurrence of anxiety-related behavior, a common co-morbid condition in individuals with impairments in social domain, suggests the presence of overlapping neurobiological mechanisms between these two pathologies. Dysregulated excitation/inhibition balance and excessive neuroinflammation, in specific neural circuits, are proposed as common etiological mechanisms implicated in both pathologies. Methods and Results: In the present study we evaluated changes in glutamatergic/GABAergic neurotransmission as well as the presence of neuroinflammation within the regions of the Social Decision-Making Network (SDMN) using a zebrafish model of NMDA receptor hypofunction, following sub-chronic MK-801 administration. MK-801-treated zebrafish are characterized by impaired social communication together with increased anxiety levels. At the molecular level, the behavioral phenotype was accompanied by increased mGluR5 and GAD67 but decreased PSD-95 protein expression levels in telencephalon and midbrain. In parallel, MK-801-treated zebrafish exhibited altered endocannabinoid signaling as indicated by the upregulation of cannabinoid receptor 1 (CB1R) in the telencephalon. Interestingly, glutamatergic dysfunction was positively correlated with social withdrawal behavior whereas defective GABAergic and endocannabinoid activity were positively associated with anxiety-like behavior. Moreover, neuronal and astrocytic IL-1ß expression was increased in regions of the SDMN, supporting the role of neuroinflammatory responses in the manifestation of MK-801 behavioral phenotype. Colocalization of interleukin-1ß (IL-1ß) with ß2-adrenergic receptors (ß2-ARs) underlies the possible influence of noradrenergic neurotransmission to increased IL-1ß expression in comorbidity between social deficits and elevated anxiety comorbidity. Discussion: Overall, our results indicate the contribution of altered excitatory and inhibitory synaptic transmission as well as excessive neuroinflammatory responses in the manifestation of social deficits and anxiety-like behavior of MK-801-treated fish, identifying possible novel targets for amelioration of these symptoms.

Neuronal and Astroglial Localization of Glucocorticoid Receptor GRα in Adult Zebrafish Brain (Danio rerio).

Glucocorticoid receptor α (GRα), a ligand-regulated transcription factor, mainly activated by cortisol in humans and fish, mediates neural allostatic and homeostatic functions induced by different types of acute and chronic stress, and systemic inflammation. Zebrafish GRα is suggested to have multiple transcriptional effects essential for normal development and survival, similarly to mammals. While sequence alignments of human, monkey, rat, and mouse GRs have shown many GRα isoforms, we questioned the protein expression profile of GRα in the adult zebrafish (Danio rerio) brain using an alternative model for stress-related neuropsychiatric research, by means of Western blot, immunohistochemistry and double immunofluorescence. Our results identified four main GRα-like immunoreactive bands (95 kDa, 60 kDa, 45 kDa and 35 kDa), with the 95 kDa protein showing highest expression in forebrain compared to midbrain and hindbrain. GRα showed a wide distribution throughout the antero-posterior zebrafish brain axis, with the most prominent labeling within the telencephalon, preoptic, hypothalamus, midbrain, brain stem, central grey, locus coeruleus and cerebellum. Double immunofluorescence revealed that GRα is coexpressed in TH+, ß2-AR+ and vGLUT+ neurons, suggesting the potential of GRα influences on adrenergic and glutamatergic transmission. Moreover, GRα was co-localized in midline astroglial cells (GFAP+) within the telencephalon, hypothalamus and hindbrain. Interestingly, GRα expression was evident in the brain regions involved in adaptive stress responses, social behavior, and sensory and motor integration, supporting the evolutionarily conserved features of glucocorticoid receptors in the zebrafish brain.

Prenatal Diagnosis of Williams-Beuren Syndrome Based on Suspected Fetal Hypotonia in Early Pregnancy.

In this report, we describe a rare case of prenatal diagnosis of Williams-Beuren syndrome (WBS). While the prenatal diagnosis of WBS is very rare, in the current case, WBS was diagnosed in early pregnancy. The key element was the detection of fetal hands hypotonia and generalized fetal hypotonia at 17 weeks of gestation. This led to the diagnosis of WBS by molecular karyotyping, specifically array comparative genomic hybridization (arrayCGH) of the fetal DNA. The genetic material was acquired by extraction from the fetal cells which are abundant in the amniotic fluid drawn by amniocentesis. Clinical hypotonia of the affected individuals is a clinical characteristic that is widely associated with WBS; however, fetal hypotonia has not been described as a diagnostic criterion for the prenatal diagnosis of WBS.

Thyroidectomy for the Management of Differentiated Thyroid Carcinoma and their Outcome on Early Postoperative Complications: A 6-year Single-Centre Retrospective Study.

INTRODUCTION/OBJECTIVE: Thyroid carcinoma (TC) accounts for one percent of all carcinomas, with a higher incidence in women. Although there is controversy on the selection of the best surgical treatment for differentiated TC, total thyroidectomy (TT) and subtotal thyroidectomy (STT) are still the two main surgical procedures. The aim of the present study was to evaluate the early complication rates of thyroidectomy in patients undergoing thyroid surgery at a tertiary hospital in Greece. Methods: A total of 306 patients with differentiated TC who underwent thyroid surgery were enrolled retrospectively. Patients were divided into two groups. Group A included 214 patients undergoing TT, whereas 92 patients (group B) underwent STT. Demographic details of patients, operating time, and early complications (hypoparathyroidism, hematoma, infection, temporary recurrent laryngeal nerve palsy) were noted. Results: There was no significant difference in the sex, age, and mean operating time between the two groups (P=0.47, P=0.55, and P=0.09, respectively). Either hematoma or wound infection occurred in 3 (1.4%) or 4 (1.87%) of the patients undergoing TT compared to two (2.17%) or three (3.26%) of the patients undergoing STT (P=0.63 and P=0.46, respectively). In addition, either hypoparathyroidism or temporary recurrent laryngeal nerve palsy was observed in 34 (15.89%) or 13 (6.07%) of the patients undergoing TT compared with eleven (11.96%) or nine (9.78%) of the patients undergoing STT (P=0.37 and P=0.25, respectively). Conclusions: The current study demonstrates that total thyroidectomy can be safely performed in patients with differentiated thyroid carcinoma without increasing the risk of early complications.

Ectopic breast carcinoma.

Carcinoma of the accessory breast tissue (CABT) is an extremely rare occurrence, representing 0.3% of all breast malignancies. A 65-year-old, postmenopausal woman was referred to our Breast Clinic complaining of a palpable, growing, and painful mass in her right axilla. Physical examination revealed a palpable tender mass, approximately 3 cm in size, visibly infiltrating the overlying skin area, while physical examination of the breast revealed no palpable lesions. Core biopsy of the mass was promptly scheduled, and the histological report came back positive for Nottingham Grade II NST invasive carcinoma of the breast. The patient underwent breast-conserving surgery and concomitant axillary lymph node dissection (ALND) for removal of the malignant mass. Care was taken to preserve the axillary vein and the long thoracic nerve. Closure of the axillary incision required mobilization of skin flaps to ensure optimal cosmetic results. Despite the ectopic breast tissue being a largely benign and infrequent occurrence, the breast surgeon must remain vigilant for the possibility of CABT development. At any rate, further epidemiological studies incorporating as many patients as possible are required in order to formulate recommendations on the management and prognosis of CABT. Until such guidelines exist, excision of the carcinoma, along with ALND performance, is a reasonable and justified approach to the surgical treatment of CABT.

The role of soluble urokinase plasminogen activator receptor (suPAR) in patients with cancer: a review of the current literature.

Aim Several biomarkers are currently used as diagnostic and prognostic tools in patients with cancer. Soluble urokinase plasminogen activator receptor (suPAR) is elevated in acute and chronic inflammatory procedures and several observational studies during the last 20 years have investigated its role in oncology. The purpose of this article was to review the current literature regarding suPAR's role in clinical practice. Methods A systematic literature search of PubMed, Scopus, OpenGrey and Cochrane Library databases through September 2021 was conducted using the following search terms: "supar"or "soluble urokinase plasminogen receptor" and "cancer" or "malignancy". Original articles reporting on suPAR's role in the diagnosis, prognosis and prediction of therapeutic outcomes in patients with confirmed or suspected cancer were included. Results Among 45 found articles, the most were observational cohort studies. The included studies were further categorized by cancer site. SuPAR level was higher in patients with cancer compared to healthy controls, but its diagnostic and prognostic accuracy differs depending on the site of cancer. Conclusion SuPAR has promising aspects in the field of oncology and public health and future research should further investigate its use in clinical practice. As it is elevated in different types of cancer, it could potentially serve as an adjunctive tool for the mass screening of patients with non-specific signs of cancer, but larger cohort studies that support these findings must be conducted.

Mid-term outcomes in the treatment of retroperitoneal sarcomas: a 12-year single-institution experience.

Aim To present the experience from collective data regarding patients with retroperitoneal sarcomas that have been operated in and followed up by the University General Hospital of Patras in Rion, Greece, between 2009 and 2020. Methods A retrospective analysis of adult patients treated at our hospital with a diagnosis of primary retroperitoneal sarcoma who underwent tumour resection. Results Data from 29 patients were analysed. The mean age at diagnosis was 56.1 years; 55.2% of patients were male (n=16). Liposarcomas (on histology) were identified in 19 (65.5%) patients, leiomyosarcoma six (20.7%), and other histologic subtypes in four (13.8%) patients. Tumours >5cm were presented in 27 (93.1%) patients. Negative margins were attained in 13 (44.8%) of all patients who underwent surgical resection. Five (17.2%) patients received neoadjuvant radiation, four (13.8%) postoperative radiation, and three (10.3%) patients received both chemotherapy and radiation prior to surgery with the rest of the patients being treated with surgical excision alone. A 3-year follow-up was successful in 21 (72.4%) patients; five (23.8%) patients died. In total, 16 (55.2%) patients were found to have a local recurrence, with no significant difference in patients' age, gender, tumour size, histology, negative surgical margin (Ro) resection, neoadjuvant chemotherapy, or radiation therapy. There was a significant difference in the 3-year survival rate between patients having positive or negative surgical margins (p=0.027). Conclusion The higher 3-year survival rate in patients with retroperitoneal sarcomas when achieving Ro resection warrant further investigation with a larger sample size across different institutions.

Fetal Hand Abnormalities in the First-Trimester Scan: A Report of Two Cases.

Two cases of fetal hand abnormalities are presented in this report. The first one is a case of unilateral fetal syndactyly detected in the first trimester routine scan, resulting in the early diagnosis of a severe genetic condition by invasive testing and early termination of pregnancy. By doing so, we ensured that the woman was managed in the most appropriate way. In the second case, we describe a fetus with bilateral hand polydactyly, which was combined with a cardiac defect - incompatible with extrauterine life. This was once again diagnosed during the first trimester scan. An uncomplicated termination of pregnancy was achieved in the first trimester of pregnancy.

A Young Woman with Autosomal Dominant Hyper Immunoglobulin E (job's) Syndrome Presenting with Acute Abdomen: a Case Report.

Background: Autosomal dominant hyper immunoglobulin IgE syndrome is a rare inherited condition that causes immune suppression. Objective: This case report describes a severe case of liver abscess, caused by a cavity-forming infection, secondary to Job's syndrome. Case presentation: A 25-year-old female patient was emergently referred to the surgical department, for the evaluation of acute, right-sided, upper abdominal pain, fever, and chills. The patient reported a past history of recurrent pulmonary infections as well as a prior diagnosis of Job's syndrome. An abdominal CT scan revealed a large intrahepatic cystic mass, consistent with a hepatic abscess on the right liver lobe. The patient was started on a course of antibiotics and was admitted to the surgical ward for further treatment. After much deliberation, a multidisciplinary team comprised of general surgeons, gastroenterologists, and interventional radiologists, decided upon the guided drainage of the abscess. Two pigtail catheters were used to drain the cavities. Antibiotic use was de-escalated, the patient gradually recovered, and the reported abscesses were greatly reduced in size. After 14 days of treatment, the patient was successfully released home. Conclusion: In patients with a known history of the autosomal dominant hyper-IgE syndrome, presenting with acute abdominal pain, the liver abscess must be on the top of the differential diagnosis list.

Behavioral and neurochemical profile of MK-801 adult zebrafish model: Forebrain ß2-adrenoceptors contribute to social withdrawal and anxiety-like behavior.

Deficits in social communication and interaction are core clinical symptoms characterizing multiple neuropsychiatric conditions, including autism spectrum disorder (ASD) and schizophrenia. Interestingly, elevated anxiety levels are a common comorbid psychopathology characterizing individuals with aberrant social behavior. Despite recent progress, the underlying neurobiological mechanisms that link anxiety with social withdrawal remain poorly understood. The present study developed a zebrafish pharmacological model displaying social withdrawal behavior, following a 3-h exposure to 4 µΜ (+)-MK-801, a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, for 7 days. Interestingly, MK-801-treated zebrafish displayed elevated anxiety levels along with higher frequency of stereotypical behaviors, rendering this zebrafish model appropriate to unravel a possible link of catecholaminergic and ASD-like phenotypes. MK-801-treated zebrafish showed increased telencephalic protein expression of metabotropic glutamate 5 receptor (mGluR5), dopamine transporter (DAT) and ß2-adrenergic receptors (ß2-ARs), supporting the presence of excitation/inhibition imbalance along with altered dopaminergic and noradrenergic activity. Interestingly, ß2-ARs expression, was differentially regulated across the Social Decision-Making (SDM) network nodes, exhibiting increased levels in ventral telencephalic area (Vv), a key-area integrating reward and social circuits but decreased expression in dorso-medial telencephalic area (Dm) and anterior tuberal nucleus (ATN). Moreover, the co-localization of ß2-ARs with elements of GABAergic and glutamatergic systems, as well as with GAP-43, a protein indicating increased brain plasticity potential, support the key-role of ß2-ARs in the MK-801 zebrafish social dysfunctions. Our results highlight the importance of the catecholaminergic neurotransmission in the manifestation of ASD-like behavior, representing a site of potential interventions for amelioration of ASD-like symptoms.

Long lasting effects of chronic WIN55,212-2 treatment on mesostriatal dopaminergic and cannabinoid systems in the rat brain.

Cannabinoid administration modulates dopamine transmission via an indirect, multisynaptic mechanism that includes the activation of cannabinoid type-1 receptor (CB1R). The present study evaluated in rodents, the effects of acute and chronic (20 days) WIN55,212-2 administration, a non-selective CB1R agonist, on dopamine uptake and synthesis in the mesolimbic and nigrostriatal dopaminergic pathways and associate them to its effects on the endocannabinoid system. The effect of spontaneous withdrawal, after different abstinence periods (7 days, 20 days), was also assessed. Acute and chronic administration of WIN55,212-2 decreased dopamine transporter (DAT) binding and mRNA levels, as well as tyrosine hydroxylase (TH) mRNA expression in the substantia nigra (SN) and ventral tegmental area (VTA). In the striatum, chronic WIN55,212-2 administration led to decreased protein expression of DAT and TH, whereas no alterations were observed after acute administration, suggesting a diminished dopamine uptake and synthesis after chronic agonist treatment. Furthermore, after chronic agonist treatment, we observed reduced CB1R binding and mRNA levels in SN and striatum, providing evidence for a possible regulatory role of the endocannabinoid system on dopaminergic function. Seven days after WIN55,212-2 cessation, we observed a rebound increase in mRNA, binding and total protein levels of DAT and TH in VTA, SN and striatum proposing the existence of a biphasic expression pattern, which was also observed in CB1R binding levels. Within the 20-day period of abstinence, TH mRNA and protein levels and CB1R binding levels remain increased. The above results indicate that chronic CB1R agonist treatment induces long-lasting control of the mesostriatal dopaminergic activity.