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Glioblastoma multiforme (GBM) is a diffuse brain tumor characterized by high infiltration in the brain parenchyma rendering the tumor difficult to eradicate by neurosurgery. Efforts to identify molecular targets involved in the invasive behavior of GBM suggested ion channel inhibition as a promising therapeutic approach. To determine if the Ca(2+)-dependent K(+) channel KCa3.1 could represent a key element for GBM brain infiltration, human GL-15 cells were xenografted into the brain of SCID mice that were then treated with the specific KCa3.1 blocker TRAM-34 (1-((2-chlorophenyl) (diphenyl)methyl)-1H-pyrazole). After 5 weeks of treatment, immunofluorescence analyses of cerebral slices revealed reduced tumor infiltration and astrogliosis surrounding the tumor, compared with untreated mice. Significant reduction of tumor infiltration was also observed in the brain of mice transplanted with KCa3.1-silenced GL-15 cells, indicating a direct effect of TRAM-34 on GBM-expressed KCa3.1 channels. As KCa3.1 channels are also expressed on microglia, we investigated the effects of TRAM-34 on microglia activation in GL-15 transplanted mice and found a reduction of CD68 staining in treated mice. Similar results were observed in vitro where TRAM-34 reduced both phagocytosis and chemotactic activity of primary microglia exposed to GBM-conditioned medium. Taken together, these results indicate that KCa3.1 activity has an important role in GBM invasiveness in vivo and that its inhibition directly affects glioma cell migration and reduces astrocytosis and microglia activation in response to tumor-released factors. KCa3.1 channel inhibition therefore constitutes a potential novel therapeutic approach to reduce GBM spreading into the surrounding tissue.

The importance of evidence for every branch of medicine in teaching in order to orient the practitioners among the great amount of most actual scientific information's, and to support clinical decisions, is well established in health care, including dentistry. The practice of evidence-based medicine is a process of lifelong, self-directed, problem-based learning which leads to the need for clinically important information about diagnosis, prognosis, therapy and other clinical and health care issues. Nowadays the practice of dentistry is becoming more complex and challenging because of the continually changing in dental materials and equipments, an increasingly litigious society, an increase in the emphasis of continuing professional development, the information explosion and the consumer movement associated with advances on the Internet. The need for reliable information and the electronic revolution have come together to allow the “paradigm shift” towards evidence-based health care. Recent years have seen an increase in the importance of evidence-based dentistry, aiming to reduce to the maximum the gap between clinical research and real world dental practice. Aim of evidence-based practice is the systematic literature review, which synthesizes the best evidences and provides the basis for clinical practice guidelines. These practice guidelines give a brief review of what evidence-based dentistry is and how to use it.

Pharmacotherapeutic strategies have been difficult to develop for several forms of temporal lobe epilepsy, which are consequently treated by surgical resection. To examine this problem, we have studied the properties of transmitter receptors of tissues removed during surgical treatment. We find that when cell membranes, isolated from the temporal neocortex of patients afflicted with drug-resistant mesial temporal lobe epilepsy (TLE), are injected into frog oocytes they acquire GABA type A receptors (GABAA-receptors) that display a marked rundown during repetitive applications of GABA. In contrast, GABAA-receptor function is stable in oocytes injected with cell membranes isolated from the temporal lobe of TLE patients afflicted with neoplastic, dysgenetic, traumatic, or ischemic temporal lesions (lesional TLE, LTLE). Use-dependent GABAA-receptor rundown is also found in the pyramidal neurons of TLE neocortical slices and is antagonized by BDNF. Pyramidal neurons in cortical slices of a traumatic LTLE patient did not show GABAA-receptor rundown. However, the apparent affinity of GABAA-receptor in oocytes microtransplanted with membranes from all of the epileptic patients studied was smaller than the affinity of receptors transplanted from the nonepileptic brain. We conclude that the use-dependent rundown of neocortical GABAAreceptor represents a TLE-specific dysfunction, whereas the reduced affinity may be a general feature of brains of both TLE and LTLE patients, and we speculate that our findings may help to develop new treatments for TLE and LTLE. human slices | Xenopus oocytes

Cell membranes isolated from brain tissues, obtained surgically from six patients afflicted with drug-resistant temporal lobe epilepsy and from one nonepileptic patient afflicted with a cerebral oligodendroglioma, were injected into frog oocytes. By using this approach, the oocytes acquire human GAB[A.sub.A] receptors, and we have shown previously that the 'epileptic receptors' (receptors transplanted from epileptic brains) display a marked run-down during repetitive applications of GABA. It was found that exposure to the neurotrophin BDNF increased the amplitude of the 'GABA currents' (currents elicited by GABA) generated by the epileptic receptors and decreased their run-down; both events being blocked by K252A, a neurotrophin tyrosine kinase receptor B inhibitor. These effects of BDNF were not mimicked by nerve growth factor. In contrast, the GAB[A.SUB.A] receptors transplanted from the nonepileptic human hippocampal uncus (obtained during surgical resection as part of the nontumoral tissue from the oligodendroglioma margins) or receptors expressed by injecting rat recombinant [alpha]1[beta]2[gamma]2 GAB[A.SUB.A] receptor subunit cDNAs generated GABA currents whose time-course and run-down were not altered by BDNF. Loading the oocytes with the [Ca.sup.2+] chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate-acetoxymethyl ester (BAPTA-AM), or treating them with Rp-8-Br-cAMP, an inhibitor of the cAMP-dependent PKA, did not alter the GABA currents. However, staurosporine (a broad spectrum PK inhibitor), bisindolylmaleimide I (a PKC inhibitor), and U73122 (a phospholipase C inhibitor) blocked the BDNF-induced effects on the epileptic GABA currents. Our results indicate that BDNF potentiates the epileptic GAB[A.SUB.A] currents and antagonizes their use-dependent run-down, thus strengthening GABAergic inhibition, probably by means of activation of tyrosine kinase receptor B receptors and of both PLC and PKC. microtransplantation into Xenopus oocytes | temporal lobe epilepsy

The properties of [gamma]-aminobutyric acid (GABA) type A receptors (GAB[A.sub.A] receptors) microtransplanted from the human epileptic brain to the plasma membrane of Xenopus oocytes were compared with those recorded directly from neurons, or glial cells, in human brains slices. Cell membranes isolated from brain specimens, surgically obtained from six patients afflicted with drug-resistant temporal lobe epilepsy (TLE) were injected into frog oocytes. Within a few hours, these oocytes acquired GAB[A.sub.A] receptors that generated GABA currents with an unusual run-down, which was inhibited by orthovanadate and okadaic acid. In contrast, receptors derived from membranes of a nonepileptic hippocampal uncus, membranes from mouse brain, or recombinant rat [alpha]1[beta]2[gamma]2-GABA receptors exhibited a much less pronounced GABA-current rundown. Moreover, the GAB[A.sub.A] receptors of pyramidal neurons in temporal neocortex slices from the same six epileptic patients exhibited a stronger run-down than the receptors of rat pyramidal neurons. Interestingly, the GAB[A.sub.A] receptors of neighboring glial cells remained substantially stable after repetitive activation. Therefore, the excessive GABA-current run-down observed in the membrane-injected oocytes recapitulates essentially what occurs in neurons, rather than in glial cells. Quantitative RT-PCR analyses from the same TLE neocortex specimens revealed that GAB[A.sub.A]receptor [beta]1, [beta]2, [beta]3, and [gamma]2 subunit mRNAs were significantly overexpressed (8- to 33-fold) compared with control autopsy tissues. Our results suggest that an abnormal GABA-receptor subunit transcription in the TLE brain leads to the expression of run-down-enhanced GAB[A.sub.A] receptors. Blockage of phospbatases stabilizes the TLE GAB[A.sub.A] receptors and strengthens GABAergic inhibition. It may be that this process can be targeted to develop new treatments for intractable epilepsy. temporal lobe epilepsy | microtransplantation into Xenopus oocyte | okadaic acid | [gamma]-aminobutyric acid-current run-down | human tissue slices

Cell membranes isolated from brain tissues, obtained surgically from six patients afflicted with drug-resistant temporal lobe epilepsy and from one nonepileptic patient afflicted with a cerebral oligodendroglioma, were injected into frog oocytes. By using this approach, the oocytes acquire human GABAA receptors, and we have shown previously that the "epileptic receptors" (receptors transplanted from epileptic brains) display a marked run-down during repetitive applications of GABA. It was found that exposure to the neurotrophin BDNF increased the amplitude of the "GABA currents" (currents elicited by GABA) generated by the epileptic receptors and decreased their run-down; both events being blocked by K252A, a neurotrophin tyrosine kinase receptor B inhibitor. These effects of BDNF were not mimicked by nerve growth factor. In contrast, the GABAA receptors transplanted from the nonepileptic human hippocampal uncus (obtained during surgical resection as part of the nontumoral tissue from the oligo- dendroglioma margins) or receptors expressed by injecting rat recombinant αβ27gamma;2 GABAA receptor subunit cDNAs generated GABA currents whose time-course and run-down were not altered by BDNF. Loading the oocytes with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N' -tetraacetate-acetoxymethyl ester (BAPTA-AM), or treating them with Rp-8-Br-cAMP, an inhibitor of the cAMP-dependent PKA, did not alter the GABA currents. However, staurosporine (a broad spectrum PK inhibitor), bisindolylmaleimide I (a PKC inhibitor), and U73122 (a phospholipase C inhibitor) blocked the BDNF-induced effects on the epileptic GABA currents. Our results indicate that BDNF potentiates the epileptic GABAA currents and antagonizes their use-dependent run-down, thus strengthening GABAergic inhibition, probably by means of activation of tyrosine kinase receptor B receptors and of both PLC and PKC. [ABSTRACT FROM AUTHOR]

Pilonidal Sinus is a benign, chronic disease that affects the hair follicles of the natal cleft of the sacrococcygeal area. Its ideal treatment is controversial, especially in complex or recurrent cases. The aim of this study is to evaluate the use of minimally invasive endoscopic approach in this setting. We enrolled patients affected by complex or recurrent sacrococcygeal pilonidal sinus from January 2015 through December 2020 who underwent Video-Assisted Ablation of Pilonidal Sinus. All patients enrolled were re-evaluated once a year with a standard physical examination. The patients included were 38. Recurrence rate at 1-, 3- and 5-years follow-ups were 28.9%, 22.2% and 38.1% respectively. Of interest, the mean (SD) distance from the most lateral orifice to the midline was higher in group of patients with recurrence and the multivariate analysis demonstrated that it was the limiting factor, which influences the recurrence rate. In complex or recurrent pilonidal sinus disease with pits off the midline the endoscopic approach should not be the first choice. This makes us think that these cases should have their own classification to be identified and guide surgeons in choosing the appropriate approach., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Purposes: The aim of this study was to evaluate the importance of Indocyanine Green in control of anastomosis perfusion and on anastomotic leakage rates during laparoscopic and robotic colorectal procedures., Methods: A retrospective review of patients who underwent elective minimally invasive surgery for colorectal cancer from 1 January 2018 to 31 December 2020 was performed. All patients underwent Near-Infrared Fluorescence-Indocyanine Green system in two moments: before performing the anastomosis and after completing the anastomotic procedure. Primary outcomes were the rate of intraoperative change in the surgical resection due to an inadequate vascularization and the rate of postoperative anastomotic leakage. Secondary outcomes were the postoperative complications, both medical and surgical (intra-abdominal bleeding, anastomotic leakage)., Results: Our analysis included 93 patients. Visible fluorescence was detected in 100% of the cases. In 7 patients (7.5%), the planned site of resection was changed due to inadequate perfusion. The mean extension of the surgical resection in these 7 patients was 2.2 ± 0.62. Anastomotic leakage occurred in 2 patients (2.1%). Other complications included 8 postoperative bleedings (8.6%) and 1 pulmonary thromboembolism., Conclusions: The intraoperative use of Near-Infrared Fluorescence-Indocyanine Green in colorectal surgery is safe, feasible, and associated with a substantial reduction in postoperative anastomotic leakage rate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maione, Manigrasso, Chini, Vertaldi, Anoldo, D'Amore, Marello, Sorrentino, Cantore, Maione, Gennarelli, D'Angelo, D'Alesio, De Simone, Servillo, Milone and De Palma.)

Introduction: Although carcinomatous degeneration is a rare occurrence, some authors support the need for a histopathological examination after pilonidal cyst excision. Today, minimally invasive techniques are widely spread for the treatment of pilonidal sinus disease but opposed to standard procedures, these techniques could not allow to perform a histopathological examination because of the absence of a specimen. The aim of this two-institutions study is to evaluate whether histopathological examination of the pilonidal sinus excision material can be successfully performed after an endoscopic ablation of the cyst., Materials and Methods: We identified all consecutive patients from January 2021 to September 2021 with diagnosis of pilonidal sinus disease who underwent Video Assisted Ablation of Pilonidal Sinus (VAAPS) followed by histopathological examination., Results: A total of 45 patients were included in the study. All patients were Caucasians and aged below 50 years. Nine of them underwent surgery due to recurrence of PSD. No evidence of malignancy was detected in the histopathological examination of the pilonidal sinus sampling material., Discussion: We were able to send pilonidal sinus sampling material for a histopathological examination in all patients who underwent minimally invasive technique for the treatment of pilonidal sinus disease. No evidence of malignancy was found in any of the 45 samples. Our findings prove that minimally invasive ablation of pilonidal sinus does not preclude histopathological examination of the cysts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vertaldi, Anoldo, Cantore, Chini, D'Amore, D'Armiento, Gennarelli, Maione, Manigrasso, Marello, Schettino, Sorrentino, Sosa Fernandez, De Palma and Milone.)

Colorectal cancer is an important cause of morbidity and mortality worldwide. Optical colonoscopy (OC) is widely accepted as the reference standard for the screening of colorectal polyps and cancers, and computed tomography colonography (CTC) is a valid alternative to OC. The purpose of this review was to assess the diagnostic accuracy of OC and CTC for colorectal lesions. A literature search was performed in PubMed, Embase, and Cochrane Library, and 18 articles were included. CTC has emerged in recent years as a potential screening examination with high accuracy for the detection of colorectal lesions. However, the clinical application of CTC as a screening technique is limited because it is highly dependent on the size of the lesions and has poor performance in detecting individual lesions <5 mm or flat lesions, which, although rarely, can have a malignant potential.