Role of Memantine in Limiting Cochleotoxicity in Rats.

Οur aim was to test whether amikacin's well-known cochleotoxic effects could be suppressed, depending on whether an NMDA-antagonist (memantine) was administered simultaneously with or after amikacin treatment. Forty Wistar rats were used in this experiment. Ten rats acted as controls and received no medication (group A). Amikacin (200 mg/kg) was administered intraperitoneally (i.p.) once daily for 14 days to 10 animals in group B; amikacin (200 mg/kg) was administered concurrently with memantine (10 mg/kg, i.p., once daily) to the same 10 animals in group C. Group D was given intraperitoneal memantine (10 mg/kg, once daily) for 14 days following a 2-week amikacin treatment. The cochlear activity of the right ear was tested using DPOAE in conscious animals. All animals were sacrificed at the conclusion of the experiment and both cochleae were collected for histological and immunohistochemical analysis. All groups treated with amikacin showed decreased cochlear activity, as testified by decreased DPOAE-amplitudes compared to the pre-treatment state. In the rats of group B, the DPOAE reduction was more pronounced. On histologic exam, the cochlear structures of group C rats and, although to a lesser extent, group D rats showed less severe cochlea damage. Memantine plays a protective role, resulting in restoring partially cochlear structures when administered either simultaneously with or after completion of amikacin i.p. treatment in rats.

Contact Endoscopic Surface Vascular and Epithelial Morphology in Leukoplakia and Carcinoma of the Vocal Cords: Vascular and morphological changes of vocal folds in leukoplakia and cancer.

Purpose Leukoplakia is a macroscopic morphological term for thick white or grey mucosal patches that can represent various histologic diagnostic entities ranging from hyperplasia to malignancy. Aim was the study morphology of the superficial mucosa and microvascular network of the vocal cords in patients with suspected glottic squamous cell carcinoma (SCC) using contact endoscopy (CE). Material and Methods Seventy-nine patients (21 female, 58 male), with a mean age of 57.5 years ± 7.12 (range, 32-73 years), were prospectively enrolled and evaluated. Of these patients, 58 had leukoplakia (Group A/41 males and 17 females, with a mean age of 53.7 years ± 6.65), and 21 (Group B/ 17males and 4 females/ with a mean age of 60.5 years ± 6.04) had malignant lesions (pT1, n = 6; p T2, n = 8; pT3, n = 8; Group B), as proven by the results of the histological examination. Further, 79 non-smokers (control group-group C) were studied. CE imaging findings were classified into five types (I to V) based on the features of the mucosal intra-epithelial capillary loops. CE findings were correlated to the histologic findings. A separate analysis involving smoking status was done. Results The CE-based intraepithelial papillary capillary loop classification score was strongly correlated with the histological findings. Age was strongly associated with both malignancy and bilateral involvement. Smoking habits didn't significantly differ between patients with unilateral and bilateral SCC. Conclusions CE imaging of the vocal cord mucosal capillaries may be useful for the early detection of glottic SCC and pre-cancerous lesions.

Enhanced medullary and extramedullary granulopoiesis sustain the inflammatory response in lupus nephritis.

OBJECTIVES: In SLE, deregulation of haematopoiesis is characterised by inflammatory priming and myeloid skewing of haematopoietic stem and progenitor cells (HSPCs). We sought to investigate the role of extramedullary haematopoiesis (EMH) as a key player for tissue injury in systemic autoimmune disorders. METHODS: Transcriptomic analysis of bone marrow (BM)-derived HSPCs from patients with SLE and NZBW/F1 lupus-prone mice was performed in combination with DNA methylation profile. Trained immunity (TI) was induced through ß-glucan administration to the NZBW/F1 lupus-prone model. Disease activity was assessed through lupus nephritis (LN) histological grading. Colony-forming unit assay and adoptive cell transfer were used to assess HSPCs functionalities. RESULTS: Transcriptomic analysis shows that splenic HSPCs carry a higher inflammatory potential compared with their BM counterparts. Further induction of TI, through ß-glucan administration, exacerbates splenic EMH, accentuates myeloid skewing and worsens LN. Methylomic analysis of BM-derived HSPCs demonstrates myeloid skewing which is in part driven by epigenetic tinkering. Importantly, transcriptomic analysis of human SLE BM-derived HSPCs demonstrates similar findings to those observed in diseased mice. CONCLUSIONS: These data support a key role of granulocytes derived from primed HSPCs both at medullary and extramedullary sites in the pathogenesis of LN. EMH and TI contribute to SLE by sustaining the systemic inflammatory response and increasing the risk for flare.

Salicylate- and Noise-induced Tinnitus. Different Mechanisms Producing the same Result? An Experimental Model.

PURPOSE: Tinnitus, the generation of phantom sounds, can be the result of noise exposure, however, understanding of its underlying mechanisms is limited. Purpose of the study was is to determine whether different concentrations of salicylate can cause tinnitus of different intensity. METHODS: For the purposes of this study 50 male Wistar rats were used. The animals were divided into 5 groups (10 rats in each group). The animals that did not receive any substance were allocated to the control group (Group A). The second group (Group B) of rats received salicylate (Sigma Aldrich) intraperitoneally for 7 days (300 mg/Kg/day). The 3rd group (Group C) received salicylate intraperitoneally for 7 days, but at twice the concentration of the animals in the second group (600 mg/kg/d). The 4th group (Group D) simultaneously received salicylate (300 mg/Kg/day) and pure Memantine (Sigma Aldrich, 10 mg/kg/d) intraperitoneally for 7 days. The 5th group (Group E) did not receive any substance but was exposed for 168 consecutive hours (7 days) to sound to induce tinnitus. Cochlear activity was evaluated with the use of Distortion Product Otoacoustic Emissions (DPOAEs). At the end of the experimental period, the animals were sacrificed, and the right cochlea was removed and prepared for further histological and immunohistochemical studies. RESULTS: The DPOAEs of animals treated either with salicylate as monotherapy or salicylate combined with memantine were indistinguishable from the noise floor, did not differ significantly compared to the animals of the control group or those expose to constant noise. The cochlear structures of Group E remained anatomically and functionally unaffected from the exposure to constant noise. Memantine does not seem to offer substantial protection to the cochlear structures, according to histological examination and hearing tests, however, the rats receiving it exhibited better results in behavioral tests. CONCLUSIONS: The administration of memantine does not contribute significantly to the reduction of tinnitus.

Association of cytokine gene polymorphisms with peripheral neuropathy susceptibility in people living with HIV in Greece.

Relatively little research has been done in recent years to understand what leads to the unceasingly high rates of HIV sensory neuropathy despite successful antiretroviral treatment. In vivo and in vitro studies demonstrate neuronal damage induced by HIV and increasingly identified ART neurotoxicity involving mitochondrial dysfunction and innate immune system activation in peripheral nerves, ultimately all pathways resulting in enhanced pro-inflammatory cytokine secretion. Furthermore, many infectious/autoimmune/malignant diseases are influenced by the production-profile of pro-inflammatory and anti-inflammatory cytokines, due to inter-individual allelic polymorphism within cytokine gene regulatory regions. Associations of cytokine gene polymorphisms are investigated with the aim of identifying potential genetic markers for susceptibility to HIV peripheral neuropathy including ART-dependent toxic neuropathy. One hundred seventy-one people living with HIV in Northern Greece, divided into two sub-groups according to the presence/absence of peripheral neuropathy, were studied over a 5-year period. Diagnosis was based on the Brief Peripheral Neuropathy Screening. Cytokine genotyping was performed by sequence-specific primer-polymerase chain reaction. Present study findings identify age as an important risk factor (p < 0.01) and support the idea that cytokine gene polymorphisms are at least involved in HIV peripheral-neuropathy pathogenesis. Specifically, carriers of IL1a-889/rs1800587 TT genotype and IL4-1098/rs2243250 GG genotype disclosed greater relative risk for developing HIV peripheral neuropathy (OR: 2.9 and 7.7 respectively), while conversely, carriers of IL2+166/rs2069763 TT genotype yielded lower probability (OR: 3.1), all however, with marginal statistical significance. The latter, if confirmed in a larger Greek population cohort, may offer in the future novel genetic markers to identify susceptibility, while it remains significant that further ethnicity-oriented studies continue to be conducted in a similar pursuit.

Death by compaction in a robotic dumpster.

Robotic waste management automation systems are increasingly utilized around the globe as a user-friendly, ecological and hygienic alternative to waste disposal, simultaneously reducing the volume and frequency of waste collection. The present paper aims to report a case of death by compaction in an automated robotic waste management system and review relevant literature on compactor-related fatalities. The unusual fatal accident involved a 37-year-old male citizen who deliberately entered the robotic dumpster to retrieve his accidentally discarded medication. Upon entering the robotic chamber, the compaction system was automatically activated, although all safety measures were in full operation. This paper highlights the lack of standardized reporting on compactor-related mortality, which however is of importance both in terms of its social impact and public safety. These deaths occur rarely, in scattered areas of the globe, associated with various situations (e.g., occupational fatalities, homeless people, infanticide) and trash compactors of different types, technology, age, maintenance quality, warning signage and safety interlocks. In all previously reported fatalities, the technology involved was considerably older (as in conventional waste containers, garbage compaction trucks, chute-fed compactors in buildings, etc.). The case described in the present report is a rare event in both literature and international news coverage as it encompasses a fully automated technology intended for unsupervised, direct use by the public being located in public spaces where all citizens can interact with it. The aim of this report is to raise awareness and improve knowledge about safety parameters so that similar incidents can be avoided in the future.

Lipophagy-Related Protein Perilipin-3 and Resistance of Prostate Cancer to Radiation Therapy.

PURPOSE: Radiation therapy is a principal treatment modality for localized and locally advanced prostate cancer (PCa). Metabolic alterations, including lipid metabolism, may reduce treatment efficacy, resulting in tumor relapse and poor therapeutic outcome. In the current study, we investigated the role of the lipophagy-related protein perilipin-3 (PLIN3) and the lysosomal acid lipase (LAL) in PCa response to radiation therapy. METHODS AND MATERIALS: We explored the in vitro and xenograft (in NOD SCID and R2G2 mice) response to radiation of either PLIN3-depleted or LAL-depleted hormone-refractory (DU145, PC3) and hormone-responsive (22Rv1) PCa cell lines. Moreover, we evaluated the clinical role of PLIN3 and LAL protein expression in a series of PCa tissue specimens from patients treated with radical radiation therapy. RESULTS: In vitro and in vivo experiments showed reduced proliferation and strong radiosensitization of all studied PCa cell lines upon PLIN3 depletion. In vivo experiments demonstrated the significantly augmented radiation therapy efficacy upon PLIN3 depletion, resulting in extensive tissue necrosis. Overexpression of PLIN3 in tissue specimens was correlated with an increased MIB1 proliferation index, increased autophagy flux, reduced response to radiation therapy, and poor prognosis. The effect of LAL depletion on radiation therapy was of lesser importance. CONCLUSIONS: Assessment of PLIN3 expression may identify subgroups of patients with PCa who are less responsive to radiation therapy and at high risk of relapse after irradiation. Whether radiation therapy efficacy may be enhanced by concurrent autophagy or PLIN3 inhibition in this subgroup of patients demands clinical evaluation.

Significance of regional population HLA immunogenetic datasets in the efficacy of umbilical cord blood banks and marrow donor registries: a study of Cretan HLA genetic diversity.

BACKGROUND AIMS: The high genetic diversity of HLA across populations significantly confines the effectiveness of a donor or umbilical cord blood search for allogeneic hematopoietic stem cell transplantation (HSCT). This study aims to probe the HLA immunogenetic profile of the population of Crete, a Greek region with specific geographic and historical characteristics, and to investigate potential patterns in HLA distribution following comparison with the Deutsche Knochenmarkspenderdatei (DKMS) donor registry. It also aims to highlight the importance of regional public cord blood banks (PCBBs) in fulfilling HSCT needs, especially in countries with significant genetic diversity. METHODS: A cohort of 1835 samples representative of the Cretan population was typed for HLA class I (HLA-A, HLA-B, HLA-C) and class II (HLA-DRB1, HLA-DQB1, HLA-DPB1) loci by high-resolution second field next-generation sequencing. Data were compared with the respective HLA profiles of 12 DKMS populations (n = 20 032). Advanced statistical and bioinformatics methods were employed to assess specific intra- and inter-population genetic indexes associated with the regional and geographic distribution of HLA alleles and haplotypes. RESULTS: A considerable HLA allelic and haplotypic diversity was identified among the Cretan samples and between the latter and the pooled DKMS cohort. Even though the HLA allele and haplotype frequency distribution was similar to regions of close geographic proximity to Crete, a clinal distribution pattern from the northern to southern regions was identified. Significant differences were also observed between Crete and the Greek population of DKMS. CONCLUSIONS: This study provides an in-depth characterization of the HLA immunogenetic profile in Crete and reveals the importance of demographic history in HLA heterogeneity and donor selection. The novel HLA allele and haplotype frequency comparative data between the Cretan and other European populations signify the importance of regional PCBBs in prioritizing HLA diversity to efficiently promote the HSCT program at the national level and beyond.

Electrogustometry: Normative data for stimulus duration, tongue site and age decline.

OBJECTIVES: Our primary goal was to evaluate the effect of stimulus duration on electrogustometry (EGM) thresholds. Additionally, we sought to evaluate any sex-related influences and compare the above results to those of taste strips. DESIGN: Electrogustometry thresholds of various stimulus durations (0.5, 1.0, 1.5 and 2.0 seconds) were measured in 212 non-smokers (age range: 10-80 years, divided into eight age-groups) without self-reported gustatory impairment. Furthermore, taste strips chemogustometry measurements in 132 participants were performed. SETTING: Tertiary referral medical centre. PARTICIPANTS: 212 non-smokers, divided into eight age-groups participated in the study. MAIN OUTCOME MEASURES: Electrogustometry thresholds and taste strips, duration of EGM stimuli. RESULTS: Electrogustometry thresholds increased progressively with age and with stimulus duration from 0.5 to 2 seconds. This pattern was consistent in all six anatomic areas, irrespective of sex. In contrast, when using chemogustometry, no age- or sex-related differences were observed. CONCLUSIONS: Electrogustometry-threshold values increase progressively with age and with stimulus duration. Therefore, we recommend documenting stimulus duration in the future EGM recordings as it may significantly affect EGM amplitude threshold values.

Endoscopic sinus surgery outcomes in CRS: quality of life and correlations with NOSE scale in a prospective cohort study.

BACKGROUND: To evaluate the impact of endoscopic sinus surgery (ESS) on clinical outcomes, quality of life (QoL) and Nasal Obstruction and Symptom Evaluation (NOSE) scale in patients with CRSwNP and CRSsNP. An additional question that needs to be investigated is whether there is a correlation between patients at the age of relapse. METHODOLOGY/PRINCIPAL: A prospective cohort study of 150 subjects [96 males, 54 females, mean age: 51.99 ± (15.73)]. The SNOT-22 and NOSE questionnaires were used to measure the patients' QoL and their nasal blockage symptoms, respectively. Endoscopic and computerized tomography (CT) scores depicted the objective findings. RESULTS: Following ESS, the endoscopic scale showed a significant improvement in 83.85% of patients. QoL measured with SNOT-22 improved by 78.85% and with NOSE scale by 92.10%. Also, a statistically significant correlation was found between NOSE, SNOT-22 and the Lund-Kennedy scale. Recurrence was observed in 13 patients during follow-up. There was no statistically significant correlation between age, gender, smoking and recurrence tendency. Patients with baseline SNOT-22 and NOSE scores lower than 30 typically fail to obtain a clinically meaningful benefit. Patients with a rate greater than or equal to 40 achieved a minimal clinically important difference (MCID) of 83.9% and had an average symptom reduction (RI) rate of 60.3%. CONCLUSIONS: ESS is an important treatment option for symptomatic patients with CRSwNP and CRSsNP. Both objective and subjective measurements including QoL improved significantly, and the results stabilized at 12 to 18 months. The NOSE scale is a sensitive outcome measure in the CRS population, including subjects with and without nasal polyps. In our study, SNOT-22 and NOSE are excellent predictors of postoperative improvement.

Transcriptome reprogramming and myeloid skewing in haematopoietic stem and progenitor cells in systemic lupus erythematosus.

OBJECTIVES: Haematopoietic stem and progenitor cells (HSPCs) are multipotent cells giving rise to both myeloid and lymphoid cell lineages. We reasoned that the aberrancies of immune cells in systemic lupus erythematosus (SLE) could be traced back to HSPCs. METHODS: A global gene expression map of bone marrow (BM)-derived HSPCs was completed by RNA sequencing followed by pathway and enrichment analysis. The cell cycle status and apoptosis status of HSPCs were assessed by flow cytometry, while DNA damage was assessed via immunofluorescence. RESULTS: Transcriptomic analysis of Lin-Sca-1+c-Kit+ haematopoietic progenitors from diseased lupus mice demonstrated a strong myeloid signature with expanded frequencies of common myeloid progenitors (CMPs)-but not of common lymphoid progenitors-reminiscent of a 'trained immunity' signature. CMP profiling revealed an intense transcriptome reprogramming with suppression of granulocytic regulators indicative of a differentiation arrest with downregulation trend of major regulators such as Cebpe, Cebpd and Csf3r, and disturbed myelopoiesis. Despite the differentiation arrest, frequencies of BM neutrophils were markedly increased in diseased mice, suggesting an alternative granulopoiesis pathway. In patients with SLE with severe disease, haematopoietic progenitor cells (CD34+) demonstrated enhanced proliferation, cell differentiation and transcriptional activation of cytokines and chemokines that drive differentiation towards myelopoiesis, thus mirroring the murine data. CONCLUSIONS: Aberrancies of immune cells in SLE can be traced back to the BM HSPCs. Priming of HSPCs and aberrant regulation of myelopoiesis may contribute to inflammation and risk of flare. TRIAL REGISTRATION NUMBER: 4948/19-07-2016.

Does Nationality Matter for the Gunshot Brain Injury? Ten-Year Retrospective Observational Cadaveric Comparative Study for Gunshot TBI between Greece and Bulgaria.

OBJECTIVE: Penetrating brain trauma (PBT) caused by gunshot is one of the most lethal traumatic brain injuries (TBIs) and its management and confrontation is of great importance. METHODS: The authors searched retrospectively the archives from 2 similar autonomous laboratories of forensic science and toxicology in the Balkan peninsula for a 10-year period of time and included only fatal penetrating brain injuries. RESULTS: The study is conducted in 61 cadavers with gunshot PBT. All of the cadavers were victims of suicide attempt. The most common anatomical localization on the skull were the facial bones, followed by skull base, temporal and parietal bone, conducting a trajectory of the gunshot. Additional findings were atherosclerosis of the blood vessels and chronic diseases such as chronic obstructive pulmonary disease, cancer and fatty liver. CONCLUSION: PBI has a high mortality rate. There are factors and findings from the collected data differing between the 2 aforementioned nations. Either way, better preventative measures, gun control and healthcare system are highly necessary.

Foreign Bodies in the Abdominal Area: Review of the Literature.

The aim of this paper is to update and summarize the relevant literature on the anatomical localization, incidence, and diagnostic and therapeutic approaches to abdominal foreign bodies. A comprehensive review was carried out on recorded cases related to the presence of foreign bodies in the abdominal area throughout the literature. Moreover, the phenomenon was discussed in relation to different patient categories associated with childhood, mental or neurological illness, incarceration, and drug trafficking as well as sexual accident or abuse. Particular importance is ascribed to the underlying psychopathology and motivation of foreign body ingestion in each category of patients. The surgical, psychiatric and legal implications of the issue are discussed in detail.

Single anterior cervical discectomy and fusion (ACDF) using self- locking stand-alone polyetheretherketone (PEEK) cage: evaluation of pain and health-related quality of life.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) constitutes the conventional treatment of cervical disc herniation due to degenerative disc disease (DDD). ACDF with plating presents a variety of complications postoperatively and stand-alone cages are thought to be a promising alternative. The aim of this study was firstly, to analyze prospectively collected data from a sample of patients treated with single ACDF using C-Plus self-locking stand-alone PEEK cage system, without the use of plates or screws, in order to evaluate pain levels of patients, utilizing Neck and Arm Pain scale as an expression of visual analogue scale (VAS). Secondly, we aimed to evaluate health-related quality of life, via the short-form 36 (SF-36) and Neck Disability Index (NDI). METHODS: Thirty-six patients (19 male and 17 female) with mean age 49.6±7 years old who underwent successful single ACDF using self-locking stand-alone PEEK cage for symptomatic cervical DDD were selected for the study. Neck and Arm pain, as well as SF-36 and NDI were estimated preoperatively and 1, 3, 6, and 12 months postoperatively. Patients underwent preoperative and postoperative clinical, neurological and radiological evaluation. RESULTS: The clinical and radiological outcomes were satisfactory after a minimum 1-year follow-up. All results were statistically important (P<0.05), excluding improvement in NDI measured between 6 and 12 months. SF-36, Neck Pain, as well as Arm Pain featured gradual and constant improvement during follow-up, with best scores presenting at 12 months after surgery, while NDI reached its best at 6 months postoperatively. CONCLUSIONS: Generally, all scores showed improvement postoperatively during the different phases of the follow-up. Subsequently, ACDF using C-Plus cervical cage constitutes an effective method for cervical disc herniation treatment, in terms of postoperative improvement on pain levels and health-related quality of life and a safe alternative to the conventional method of treatment for cervical DDD.