Cerebral cortex expression of Gli3 is required for normal development of the lateral olfactory tract

<div><p>Formation of the lateral olfactory tract (LOT) and innervation of the piriform cortex represent fundamental steps to allow the transmission of olfactory information to the cerebral cortex. Several transcription factors, including the zinc finger transcription factor Gli3, influence LOT formation by controlling the development of mitral cells from which LOT axons emanate and/or by specifying the environment through which these axons navigate. <i>Gli3</i> null and hypomorphic mutants display severe defects throughout the territory covered by the developing lateral olfactory tract, making it difficult to identify specific roles for <i>Gli3</i> in its development. Here, we used <i>Emx1Cre</i>;<i>Gli3</i>^<i>fl/fl</i> conditional mutants to investigate LOT formation and colonization of the olfactory cortex in embryos in which loss of <i>Gli3</i> function is restricted to the dorsal telencephalon. These mutants form an olfactory bulb like structure which does not protrude from the telencephalic surface. Nevertheless, mitral cells are formed and their axons enter the piriform cortex though the LOT is shifted medially. Mitral axons also innervate a larger target area consistent with an enlargement of the piriform cortex and form aberrant projections into the deeper layers of the piriform cortex. No obvious differences were found in the expression patterns of key guidance cues. However, we found that an expansion of the piriform cortex temporally coincides with the arrival of LOT axons, suggesting that <i>Gli3</i> affects LOT positioning and target area innervation through controlling the development of the piriform cortex.</p></div

Mini-laparoscopic cholecystectomy with the MiniLap&reg; percutaneous surgical system: a series of 32 patients

Konstantinos Sapalidis,1 Christoforos Kosmidis,1 Nikos Michalopoulos,1 Stylianni Laskou,1 Efstathios Pavlidis,1 Stelios Mantalovas,1 Dimitrios Giannakidis,1 Aikaterini Amaniti,1 Charilaos Koulouris,1 Athanasios Katsaounis,1 Alexandru C Munteanu,1 Valeriou Surlin,1 Paul Zarogoulidis,2 Isaak Kesisoglou1 1Third Department of Surgery, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Pulmonary-Oncology Department, &ldquo;Theageneio&rdquo; Cancer Hospital, Thessaloniki, Greece Background: In recent years, mini-laparoscopic procedures are gaining the preference of most surgeons due to their potentially better surgical outcomes. The Mini Lap Percutaneous Surgical System with MiniGrip&reg; Handle is currently the less invasive instrument and can be applied to a wide range of operations. The current paper presents its application on percutaneous laparoscopic cholecystectomy. Materials and methods: From January 2017 to June 2017, 32 patients underwent percutaneous laparoscopic cholecystectomy with the MiniLap&reg; system. All operations were performed by the same surgical team. Results: No conversions and no overall complications were reported. Drainage were not necessary. Mean surgical time was 35 minutes, while patients were released in &lt;24 hours after the operation. Conclusion: The MiniLap system with the use of the mini grip handle seems to sustain the benefits of performing laparoscopically. However, further trials should be conducted so as to establish its safety on cholecystectomies. Keywords: cholecystectomy, minimally invasive surgery, MiniGrip handle, percutaneous cholecystectomy, mini-laparoscop

Design of a predictive score to assess the risk of developing hypocalcemia after total thyroidectomy. A retrospective study

Anastasios Papanastasiou,1 Konstantinos Sapalidis,1 Stylianos Mantalobas,1 Stefanos Atmatzidis,1 Nikolaos Michalopoulos,1 Valeriu Surlin,1 Athanasios Katsaounis,1 Aikaterini Amaniti,1 Paul Zarogoulidis,1 Ioannis Passos,1 Charilaos Koulouris,1 Efstathios Pavlidis,1 Dimitrios Giannakidis,1 Stelian Mogoanta,2 Christoforos Kosmidis,1 Isaak Kesisoglou113rd Department of Surgery, &ldquo;AHEPA&rdquo; University Hospital, Aristotle University of Thessaloniki, Medical School, Thessaloniki, Greece; 2Department of Surgery, Faculty of Dentistry, University of Medicine and Pharmacy of Craiova, Craiova, RomaniaBackground: Temporary hypocalcemia is the most common complication in patients after total thyroidectomy. To date, according to the literature, various predictors of the above complication have been proposed, but none of them seems to be effective enough.Objectives: The aim of this study was to develop a reliable predictive tool for biochemical hypocalcemia in the first 48 hrs after total thyroidectomy without central dissection by analyzing several parameters relevant to this operation and to suggest a new score.Methods: A retrospective study was performed on patients who had undergone total thyroidectomy without central neck dissection from October 2017 until January 2018. Data were collected from 36 patients and studied if there was a statistically significant relationship between the risk of hypocalcemia and 10 preselected prognostic factors.Results: The prognostic score was formed, which included the 6 factors that showed a statistically significant relationship. Moreover, an extensive check of the predictive value of the above score was performed. It was found, therefore, that at a value of 3 and above the sensitivity was 100%, the specificity 79.16%, the positive prognostic value (PPV) 70.58% and the negative predictive value (NPV) 100%.Conclusions: High sensitivity of CaReBe&rsquo;S TiP score makes it feasible to predict patients with postoperative hypocalcemia. High NPV would allow surgeons to exclude patients with a score less than 3 from supplementary calcium medication and achieve a shorter hospitalization for them.Keywords: design, thyroidectomy, hypocalcemia, prognostic factor

Genes’ interactions: A major contributor to the malignant transformation of endometriosis

The genetic and epigenetic factors that contribute to the malignant transformation of endometriosis are still under investigation. The objective of the present study was to investigate the genetic link between endometriosis and cancer by examining and correlating the latest clinical observations with biological experimental data. We collected updated evidence about the genetic relationship between endometriosis and cancers by conducting a comprehensive search of PubMed and Scopus databases, focusing on the papers published between January 2018 and January 2019. New insights into the mechanism of the malignant transformation of endometriosis have been published recently. The use of state-of-the-art techniques and methods, such as the genome-wide association study analysis and the weighted gene co-expression analysis, have significantly altered our understanding of the association between endometriosis and endometriosis-associated cancer development. Interestingly, the interactions formed between genes seem to play a pivotal role in the phenotypic expression of mutations. Therefore, the effect of single nucleotide polymorphisms and the function of the expression quantitative trait loci on genes’ expression have been the subject of many recent works. In addition, it has been discovered that genes, the mutations of which have been related to the development of endometriosis, play a role as hub genes. This may lead to new areas of research for understanding the mechanism of malignant transformation of the disease. Significant steps forward have been made towards the identification of factors that control the malignant transformation of endometriosis. Still, due to rarity of the event, a better-organized scheme for sampling on a global level should be adopted. © 2019 by the authors. Licensee MDPI, Basel, Switzerland

Gender differences in obstructive sleep apnea: The value of sleep questionnaires with a separate analysis of cardiovascular patients

Background: Gender affects the clinical presentation of obstructive sleep apnea (OSA). The classic OSA symptoms, such as sleepiness, snoring, and apnea, are not so frequent in women. Objectives: To evaluate possible gender differences in questionnaires used for OSA prediction, such as the Epworth Sleepiness Scale (ESS), STOP, STOP Bang (SB), Berlin Questionnaire (BQ), Athens Insomnia Scale (AIS), and Fatigue Scale (FS). Methods: 350 males were matched with 350 women referred to a sleep clinic, according to OSA severity. All responded to the questionnaires and underwent a sleep study. Cardiovascular disease (CVD) patients were separately analyzed. Results: ESS did not differ between genders. SB was higher in males, whereas STOP, BQ, AIS, and FS were higher in females. BQ presented the highest sensitivity in both genders, whereas STOP exhibited the highest specificity in males and ESS in females. AIS and FS were more sensitive and SB more specific in females, whereas BQ was more specific in males. For severe OSA, the predictive values of SB and BQ were almost similar for both genders; however AIS and FS were higher in women. CVD patients presented higher scores, independent of gender, except for AIS, which was higher in females. Conclusion: Gender-specific evaluation of questionnaires is necessary to prevent OSA under-diagnosis. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Regulation of intestinal immunity and tissue repair by enteric glia

Tissue maintenance and repair depend on the integrated activity of multiple cell types( 1 ). Whereas the contributions of epithelial( 2,3 ), immune( 4,5 ) and stromal cells( 6,7 ) in intestinal tissue integrity are well understood, the role of intrinsic neuroglia networks remains largely unknown. Here, we uncover pivotal roles of enteric glial cells (EGCs) in intestinal homeostasis, immunity and tissue repair. We demonstrate that infection of mice with Heligmosomoides polygyrus leads to enteric gliosis and upregulation of an interferon gamma (IFN-γ) gene signature. IFN-γ-dependent gene modules were also induced in EGCs from inflammatory bowel disease patients( 8 ). Single-cell transcriptomics of the tunica muscularis (TM) showed that glia-specific abrogation of IFN-γ signaling leads to tissue-wide activation of pro-inflammatory transcriptional programs. In addition, disruption of the IFN-γ-EGC signaling axis enhanced the inflammatory and granulomatous response of the TM to helminths. Mechanistically, we show that upregulation of Cxcl10 is an early immediate response of EGCs to IFN-γ signaling and provide evidence that this chemokine and the downstream amplification of IFN-γ signaling in the TM are required for a measured inflammatory response to helminths and resolution of granulomatous pathology. Our study demonstrates that IFN-γ signaling in enteric glia is central to intestinal homeostasis and reveals critical roles of the IFN-γ-EGC-Cxcl10 axis in immune response and tissue repair following infectious challenge

Late results of a randomized trial on the role of mild hypofractionated radiotherapy for the treatment of localized prostate cancer

Background: Prostate cancer is considered to be highly sensitive to changes in radiation therapy dose per fraction, specifically to hypofractionation. An increase in the fractionation dose could cause a higher increase to the prostate than to the normal tissues leading to better disease control with less toxicity. Here we present the results of a randomized trial comparing mild hypofractionation to conventional fractionation after a median of 3,6 years follow up. Patients and Methods: 139 patients were randomized to receive either hypofractionated radiotherapy with 2,25 Gy/fr to a total of 72 Gy (arm 1) or conventionally fractionated treatment with 2Gy/fr to a total of 74 Gy (arm 2). 72 patients were assigned to arm 1 and 67 to arm 2. Results: After a median follow up of 3,6 years, 23 patients (31,9%) from arm 1 developed grade≥ 2 acute genitourinary toxicity and 21 (31,3%) from arm 2 (p=0,79). The corresponding values from gastrointestinal were 15 (20,8%) and 12 (17,9%) (p=0,6). For late toxicity from GU, 8 patients (11,1%) developed grade≥ 2 symptoms in arm 1 and 7 (10,4%) in arm 2 (p=0,92). late GI toxicity grade≥ 2 was observed in 8 (11,1%) patients in arm 1 and 8 (11,9%) in arm 2 (p=0,88). In multivariate analysis, hormone therapy was significantly associated with late GI events, while acute toxicity from both GU and GI was a prognostic factor of late adverse reaction. Conclusion: No difference in the toxicity profile could be identified between hypofractionation and conventional fractionation. Our schedule of 2,25Gy/fr seems safe and tolerable by the patients with acceptable rates of acute and late toxicity. © The author(s)

The role of hypofractionated radiotherapy for the definitive treatment of localized prostate cancer: Early results of a randomized trial

Background: Prostate cancer is considered to have a special biology which could affect the radiation therapy result based on the selected fractionation scheme. We present the preliminary results of a randomized trial comparing conventionally and hypofractionated radiation therapy for prostate cancer. Methods: Patients included in the study had localized prostate cancer (cT1c-T3bN0M0) and were randomly assigned to mild hypofractionated (72 Gy in 32 fractions, arm1) or conventionally fractionated (74 Gy in 37 fractions, arm2) radiation therapy treatment with Volumetric Arc Therapy technique. The treatment was delivered only to the prostate with or without the seminal vesicles according to physician’s discretion and hormone therapy was optional according to the disease stage and comorbidities. Here we present the preliminary results of acute toxicity from the gastrointestinal (GI) and genitourinary (GU) system. Results: Between 2015 and 2016, 139 patients were enrolled. 67 patients were treated with conventional fractionation and 72 were treated with hypofractionation. Grade≥ 2 toxicity from GU and GI was observed in 23 and 21 patients (31,9% vs 31,3%, p=0,79) and 15 and 12 (20,8% vs 17,9%, p=0,6) for arm1 and arm2 respectively. No statistically significant differences were observed between arms in the incidence of early toxicity. There was no correlation observed between patient characteristics and toxicity from either GU or GI. Conclusions: Hypofractionated radiotherapy appears to be equally tolerated compared to conventional fractionation in the early setting. Longer follow up is needed to assess the late toxicity profile of the patients and any potential differences between the control and experimental arm. © The author(s)

Mortality after surgery in Europe: a 7 day cohort study

Background: Clinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe.Methods: We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ² and Fisher’s exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p&lt;0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries.Findings: We included 46 539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9–3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0–3·0] for Iceland to 21·5% [16·9–26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19 1·05; p=0·06] for Finland to 6·92 [2·37–20·27; p=0·0004] for Poland).Interpretation: The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients.Funding: European Society of Intensive Care Medicine, European Society of Anaesthesiology