CT features of pulmonary embolism in patients with COVID-19 pneumonia.

OBJECTIVE: The aim of this study was to describe the Computed Tomography (CT) features of pulmonary embolism in patients hospitalized for acute COVID-19 pneumonia and to evaluate the prognostic significance of these features. PATIENTS AND METHODS: This retrospective study included 110 consecutive patients who were hospitalized for acute COVID-19 pneumonia and underwent pulmonary computed tomography angiography (BTPA) on the basis of clinical suspicion. The diagnosis of COVID-19 infection was determined by CT findings typical of COVID-19 pneumonia and/or a positive result of a reverse transcriptase-polymerase chain reaction test. RESULTS: Of the 110 patients, 30 (27.3%) had acute pulmonary embolism and 71 (64.5%) had CT features of chronic pulmonary embolism. Of the 14 (12.7%) patients who died despite receiving therapeutic doses of heparin, 13 (92.9%) had CT features of chronic pulmonary embolism and 1 (7.1%) of acute pulmonary embolism. CT features of chronic pulmonary embolism were more common in deceased patients than in surviving patients (92.9% vs. 60.4%, p=0.01, respectively). Low oxygen saturation and high urine microalbumin creatinine ratio at admission in COVID-19 patients are important determinants of mortality after adjusting for sex and age in logistic procedures. CONCLUSIONS: CT features of chronic pulmonary embolism are common in COVID-19 patients undergoing Computed Tomography Pulmonary Angiography (CTPA) in the hospital. The coexistence of albuminuria, low oxygen saturation and CT features of chronic pulmonary embolism at admission in COVID-19 patients may herald fatal outcomes.

The effect of the COVID-19 pandemic on anesthesia techniques in tertiary hospital: general anesthesia or regional anesthesia - a retrospective cohort study.

OBJECTIVE: We aimed to find out how the pandemic process changed the anesthesia methods applied in Çorum Single Tertiary Region Hospital. In our hospital, we investigated the anesthesia methods used for surgical procedures before and during the pandemic, the number of cases, and the impact of the pandemic on emergency and elective surgeries. MATERIALS AND METHODS: This is a retrospective cohort study comparing COVID-19 pandemic's effect on the number of surgical operations and anesthesia techniques. The 22-month surgeries during the pandemic period and the 22-month pre-pandemic surgeries were compared in terms of anesthesia methods, branch-specific, and overall case changes. The data obtained were analyzed comparatively in terms of anesthetic techniques, branch-specific and overall case changes of the patients operated on in the operating room before and during the pandemic. RESULTS: While 65,984 surgical procedures were performed in the pre-pandemic period, only 54,352 were performed during the COVID-19 pandemic. The total number of surgical procedures decreased by 17.63% during the pandemic. While there was a 21.1% decrease in elective surgeries due to the pandemic, there was a 71.43% increase in emergency surgeries during the pandemic period. There was a significant disparity in the distribution of both elective and emergency cases by surgical specialty. It was found that the surgical specialties that received the most cases during the pandemic were General Surgery, Obstetrics-Gynecologic Surgery, Urologic Surgery and Orthopedic Surgery. During the COVID-19 pandemic, regional anesthesia (RA) was used in 16.95% of cases (as the primary technique). The use of RA as the primary anesthetic technique was significantly higher (10.61%) than in the pre-pandemic data. It was observed that specialties such as General Surgery, Obstetrics-Gynecologic Surgery, Urologic Surgery, And Orthopedic Surgery were prominent in the distribution of regional anesthesia. CONCLUSIONS: The COVID-19 pandemic was not the first and will not be the last and during this period we saw how important the personnel and material management are. Our study plays an important role in showing the uneven distribution of expected surgical procedures in operating rooms during the pandemic situation. It may provide guidance on the distribution of limited and essential personnel and personal protective equipment (PPE, medications, etc.) during the pandemic period. In this context, regional anesthesia may play an important role in the future because it can provide high-quality perioperative care to patients while minimizing the preference for general anesthesia during surgical procedures, thus minimizing personnel burden and limited resource use.

Tumor-derived CTF1 (cardiotrophin 1) is a critical mediator of stroma-assisted and autophagy-dependent breast cancer cell migration, invasion and metastasis.

Macroautophagy/autophagy is an evolutionarily conserved cellular stress response mechanism. Autophagy induction in the tumor microenvironment (stroma) has been shown to support tumor metabolism. However, cancer cell-derived secreted factors that initiate communication with surrounding cells and stimulate autophagy in the tumor microenvironment are not fully documented. We identified CTF1/CT-1 (cardiotrophin 1) as an activator of autophagy in fibroblasts and breast cancer-derived carcinoma-associated fibroblasts (CAFs). We showed that CTF1 stimulated phosphorylation and nuclear translocation of STAT3, initiating transcriptional activation of key autophagy proteins. Additionally, following CTF1 treatment, AMPK and ULK1 activation was observed. We provided evidence that autophagy was important for CTF1-dependent ACTA2/α-SMA accumulation, stress fiber formation and fibroblast activation. Moreover, promotion of breast cancer cell migration and invasion by activated fibroblasts depended on CTF1 and autophagy. Analysis of the expression levels of CTF1 in patient-derived breast cancer samples led us to establish a correlation between CTF1 expression and autophagy in the tumor stroma. In line with our in vitro data on cancer migration and invasion, higher levels of CTF1 expression in breast tumors was significantly associated with lymph node metastasis in patients. Therefore, CTF1 is an important mediator of tumor-stroma interactions, fibroblast activation and cancer metastasis, and autophagy plays a key role in all these cancer-related events.Abbreviations: ACTA2/α-SMA: actin, alpha 2, smooth muscle CAFs: cancer- or carcinoma-associated fibroblasts CNT Ab.: control antibody CNTF: ciliary neurotrophic factor CTF1: cardiotrophin 1 CTF1 Neut. Ab.: CTF1-specific neutralizing antibody GFP-LC3 MEF: GFP-fused to MAP1LC3 protein transgenic MEF LIF: leukemia inhibitory factor IL6: interleukin 6 MEFs: mouse embryonic fibroblasts MEF-WT: wild-type MEFs OSM: oncostatin M TGFB/TGFß: transforming growth factor beta.

Neuroprotective effects of amantadine for experimental acute carbon monoxide poisoning.

OBJECTIVE: Amantadine is known to have a neuroprotective effect in many neurological diseases. This study aims at investigating the neuroprotective effect of amantadine in rats exposed to carbon monoxide (CO) poisoning. MATERIALS AND METHODS: Rats were maintained under standard experimental laboratory conditions and randomized into 4 different groups of 7 each namely control, amantadine only, CO exposure, and amantadine + CO exposure. For immunohistochemical analysis, tissues taken from the prefrontal and hippocampal regions were taken into formalin and kept for at least one day. Afterward, the tissue was followed and blocked for paraffin blocking. N-Methyl D-Aspartate (NMDA) levels in homogenates were studied by the Enzyme-Linked Immunosorbent Assay (ELISA) method. Superoxide dismutase (SOD) and catalase (CAT) activities in the supernatants were studied with commercial kits. Nitric oxide (NO) and Asymmetric Dimethyl Arginine (ADMA) levels were studied by the ELISA method. Enzyme activity values were calculated by dividing the protein values in the supernatants and normalizing them. RESULTS: CAT, SOD, NMDA, ADMA, and NO levels were statistically significantly different between the groups (p < 0.05). According to post-hoc pairwise comparison test results, the values of the control and amantadine groups for CAT, SOD, NMDA, ADMA, and NO parameters were significantly higher than that of CO group. Similarly, values in the control and amantadine groups were considerably higher than values for the amantadine + CO group. NMDA values were significantly lower in group amantadine + CO than in CO group (p: 0.049). CONCLUSIONS: Apoptosis and endothelial damage after CO poisoning is a complex process, and amantadine administration has a limited contribution in preventing this process.

Pulmonary embolism in patients with dyspnea after COVID-19 infection.

OBJECTIVE: Pulmonary embolism as a potential complication that may occur late in the course of COVID-19 cases. The aim of our study is to evaluate the frequency of pulmonary embolism in patients with new or ongoing dyspnea after a COVID-19 infection. PATIENTS AND METHODS: This is a single-center, prospective observational study to evaluate the clinical and radiological outcomes of consecutive patients presenting outpatient clinic diseases to the chest and a new or ongoing dyspnea after a COVID-19 infection. Demographic, clinical and laboratory data were collected. Dyspnea was evaluated according to the New York Heart Association (NYHA) classification. RESULTS: Pulmonary embolism was detected in 23.8% (25/105) of patients with new or ongoing dyspnea after a COVID-19 infection. Proportion of pulmonary embolism in patients with NYHA classes I, II, III and IV were respectively 8.7%, 20.0%, 30.0% and 35.3% (p for trend=0.02). Compared to NYHA class I and II patients with dyspnea, those in NYHA classes III and IV showed a higher rate of pulmonary embolism [31.6% vs. 14.6%, OR: 2.7 (1.0 to 7.1), p=0.04, respectively]. In Logistic Procedures, NYHA classes of dyspnea (OR: 4.3, 95% CI: 1.2 to 16.6, p=0.03) (NYHA class III and IV vs. NYHA class I and II) determine the likelihood of pulmonary embolism after COVID-19 infection. CONCLUSIONS: Pulmonary embolism is common in patients with new or ongoing shortness of breath after a COVID-19 infection. Pulmonary embolism is more likely to develop in patients with higher NYHA classes.

The Protective Effect of Nigella sativa Oil against Experimentally Induced Cisplatin Ototoxicity: An Animal Study.

OBJECTIVES: The objective of this study was to investigate the potential protective effect of Nigella sativa oil (NSO) against cis-diamminedichloroplatinum or cisplatin (CDDP)-induced ototoxicity. MATERIALS AND METHODS: Twenty-four Wistar albino rats were randomly and equally divided into four groups. Groups 1 and 2 were given a total of 15 mg/kg CDDP intraperitoneally, which was divided equally into three doses on days 1, 3, and 5. Group 2 was treated via gavage feeding with 15 ml NSO that was divided into five doses on days 1, 3, 5, 7, and 9. Groups 3 and 4 received only 15 ml of NSO and 15 ml of 0.9% saline solution, respectively, which were orally administered and divided into five doses on days 1, 3, 5, 7, and 9. Baseline high-frequency (8, 12, 16, and 32 kHz) auditory brainstem response (ABR) measurements were collected in all the groups before the medical administrations and were repeated on the 14th day before sacrifice. Afterward, a histopathological evaluation of the cochlea was performed. RESULTS: There was a significant difference in the histopathological changes between group 1 and the other groups (p<0.01). Changes in the spiral ganglion cells, the stria vascularis, and the external ciliated cells were significantly different between groups 1 and 2 (p=0.019, 0.039, and 0.045, respectively). The ABR results revealed significant differences in the 16 and 32 kHz measurements between groups 1 and 2 (p=0.013 and p<0.01, respectively). CONCLUSION: According to the results, NSO may have a protective effect on cochlear function against the disruptive effects of CDDP in rats.

Inflammation-induced glycolytic switch controls suppressivity of mesenchymal stem cells via STAT1 glycosylation.

Mesenchymal stem cells (MSCs) represent key contributors to tissue homeostasis and promising therapeutics for hyperinflammatory conditions including graft-versus-host disease. Their immunomodulatory effects are controlled by microenvironmental signals. The MSCs' functional response towards inflammatory cues is known as MSC-"licensing" and includes indoleamine 2,3-dioxygenase (IDO) upregulation. MSCs use tryptophan-depleting IDO to suppress T-cells. Increasing evidence suggests that several functions are (co-)determined by the cells' metabolic commitment. MSCs are capable of both, high levels of glycolysis and of oxidative phosphorylation. Although several studies have addressed alterations of the immune regulatory phenotype elicited by inflammatory priming metabolic mechanisms controlling this process remain unknown. We demonstrate that inflammatory MSC-licensing causes metabolic shifts including enhanced glycolysis and increased fatty acid oxidation. Yet, only interfering with glycolysis impacts IDO upregulation and impedes T-cell-suppressivity. We identified the Janus kinase (JAK)/signal transducer and activator of transcription (STAT)1 pathway as a regulator of both glycolysis and IDO, and show that enhanced glucose turnover is linked to abundant STAT1 glycosylation. Inhibiting the responsible O-acetylglucosamine (O-GlcNAc) transferase abolishes STAT1 activity together with IDO upregulation. Our data suggest that STAT1-O-GlcNAcylation increases its stability towards degradation thus sustaining downstream effects. This pathway could represent a target for interventions aiming to enhance the MSCs' immunoregulatory potency.

Saliva samples as a source of DNA for high throughput genotyping: an acceptable and sufficient means in improvement of risk estimation throughout mammographic diagnostics.

BACKGROUND: Breast cancer screening programs seem to be an insufficient tool for women at high genetic risk for breast cancer. These women are not adequately monitored yet. Genetic testing may improve clearly the quality of breast cancer prevention programs. At present, blood samples are favored for obtaining high-quality DNA; however, DNA can also be obtained by collecting saliva. The aim of this study was, on the one hand, to determine whether saliva sampling is a practicable means to obtain sufficient quantity and quality of DNA and, on the other hand, whether it is accepted by patients throughout mammographic diagnostics. METHODS: 67 consecutive women with diagnostic need for mammography with or without a family history for breast cancer were asked for their basic willingness to undergo a genetic testing by saliva sample in addition to standard diagnostics. Saliva samples were analyzed in terms of DNA quantity and quality. RESULTS: 64 (95.6%) women agreed to provide a saliva sample; 3 of them denied participation. And even 63 out of 64 (98.4%) were interested in their specific results. 45 out of 64 samples contained a DNA concentration above 50 ng/µl, 12 samples were between 25 and 50 ng/µl and only 7 of them were under 25 ng/µl with the standard extraction procedure. CONCLUSION: A high number of patients seem to accept salvia samples as a risk assessment tool in breast diagnostics and are interested in their specific risk situation. At the same time, it could be demonstrated that it is an effective way to provide high-quality DNA for breast cancer gene analysis. However, it remains to be shown whether it would be possible to integrate it with the same acceptance in a nationwide breast cancer screening program.

Characterization of germ cell differentiation in the male mouse through single-cell RNA sequencing.

Spermatogenesis in the mouse has been extensively studied for decades. Previous methods, such as histological staining or bulk transcriptome analysis, either lacked resolution at the single-cell level or were focused on a very narrowly defined set of factors. Here, we present the first comprehensive, unbiased single-cell transcriptomic view of mouse spermatogenesis. Our single-cell RNA-seq (scRNA-seq) data on over 2,500 cells from the mouse testis improves upon stage marker detection and validation, capturing the continuity of differentiation rather than artificially chosen stages. scRNA-seq also enables the analysis of rare cell populations masked in bulk sequencing data and reveals new insights into the regulation of sex chromosomes during spermatogenesis. Our data provide the basis for further studies in the field, for the first time providing a high-resolution reference of transcriptional processes during mouse spermatogenesis.

Retreatability of root canals obturated using mineral trioxide aggregate-based and two resin-based sealers.

BACKGROUND: The aim of this study was to compare the retreatment time and the removal efficiency of different root canal sealers using WaveOne Gold reciproc file system by measuring required time. MATERIALS AND METHODS: Forty-five mandibular premolars were prepared and randomly divided into three groups (n = 15). In Groups 1-3, the canals were filled with gutta-percha and mineral trioxide aggregate (MTA) Fillapex, EndoREZ, and AH26, respectively. After 7 days, root canal filling materials (RCFM) were removed with WaveOne Gold reciproc files by measuring time. Teeth were grooved and sectioned longitudinally, then remaining RCFM was evaluated using digital camera. The images were transferred to image analysis software to measure the areas of remaining RCFM. Data were analyzed using one-way analysis of variance and Tukey's test (α = 0.05). RESULTS: There was a statistically significant difference between groups according to time required for removing RCFM (P < 0.05). The time required for removing RCFM was significantly shorter in Group 1 and longer in Group 3 than the other groups (P < 0.05). In Group 1, the remaining RCFM was more than other groups at middle third (P < 0.05), but there was no statistically significant difference between groups at coronal and apical thirds (P > 0.05). CONCLUSIONS: None of the sealers evaluated in this study could completely be removed from the root canals. MTA-based sealer was removed faster than resin-based sealers.

Evaluation of the Possible Neurotoxic Effect of the Bone Cement on the Facial Nerve: An Experimental Study.

OBJECTIVES: To investigate neurotoxic effect of bone cement (BC) on facial nerve by using electrophysiological and histopathological methods. METHODS: This study included 20 male albino Wistar rats, divided into four equal groups. Group A was designed as the control group, while group B was sham group. In the group C, BC solution was dropped onto the facial nerve trunks of rats and washed with physiological saline after 5 seconds. In the group D, BC solution was dropped onto the facial nerve trunks of rats and after allowing 5 minutes to dry, wounds were closed. Pre- and postoperative (on 4th week) evoked electromyography (EMG) measurements were done. For histopathological assessments, the rats were euthanized and tissue samples of facial nerve and surrounding areas were collected. RESULTS: According to the wave amplitude levels of evoked EMG, postoperative amplitude levels of group D were significantly decreased, compared to preoperative amplitude levels (P=0.043). We found no statistically significant difference in inflammation among the groups. In none of the groups, foreign body reaction and granulation tissue were not detected in any of the groups. In addition, degeneration in axon, myelin, or perineural nets was not detected in any of the groups. CONCLUSION: This study results suggest that BC has no direct toxicity on facial nerve, while it has indirect effects, by decreasing amplitude. Therefore, we conclude that direct contact of BC with nerve should be avoided, and the area should be cleaned by aspiration or washing with physiological saline in case of contact.

EFhd2/Swiprosin-1 is a common genetic determinator for sensation-seeking/low anxiety and alcohol addiction.

In many societies, the majority of adults regularly consume alcohol. However, only a small proportion develops alcohol addiction. Individuals at risk often show a high sensation-seeking/low-anxiety behavioural phenotype. Here we asked which role EF hand domain containing 2 (EFhd2; Swiprosin-1) plays in the control of alcohol addiction-associated behaviours. EFhd2 knockout (KO) mice drink more alcohol than controls and spontaneously escalate their consumption. This coincided with a sensation-seeking and low-anxiety phenotype. A reversal of the behavioural phenotype with ß-carboline, an anxiogenic inverse benzodiazepine receptor agonist, normalized alcohol preference in EFhd2 KO mice, demonstrating an EFhd2-driven relationship between personality traits and alcohol preference. These findings were confirmed in a human sample where we observed a positive association of the EFhd2 single-nucleotide polymorphism rs112146896 with lifetime drinking and a negative association with anxiety in healthy adolescents. The lack of EFhd2 reduced extracellular dopamine levels in the brain, but enhanced responses to alcohol. In confirmation, gene expression analysis revealed reduced tyrosine hydroxylase expression and the regulation of genes involved in cortex development, Eomes and Pax6, in EFhd2 KO cortices. These findings were corroborated in Xenopus tadpoles by EFhd2 knockdown. Magnetic resonance imaging (MRI) in mice showed that a lack of EFhd2 reduces cortical volume in adults. Moreover, human MRI confirmed the negative association between lifetime alcohol drinking and superior frontal gyrus volume. We propose that EFhd2 is a conserved resilience factor against alcohol consumption and its escalation, working through Pax6/Eomes. Reduced EFhd2 function induces high-risk personality traits of sensation-seeking/low anxiety associated with enhanced alcohol consumption, which may be related to cortex function.

Genetic Breast Cancer Susceptibility Variants and Prognosis in the Prospectively Randomized SUCCESS A Study.

Large-scale genotyping studies have identified over 70 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. However, knowledge regarding genetic risk factors associated with the prognosis is limited. The aim of this study was therefore to investigate the prognostic effect of nine known breast cancer risk SNPs. BC patients (n = 1687) randomly sampled in an adjuvant, randomized phase III trial (SUCCESS A study) were genotyped for nine BC risk SNPs: rs17468277 (CASP8) , rs2981582 (FGFR2) , rs13281615(8q24), rs3817198 (LSP1) , rs889312 (MAP3K1) , rs3803662 (TOX3) , rs13387042(2q35), rs4973768 (SLC4A7) , rs6504950 (COX11) . Cox proportional hazards models were used to test the SNPs' association with overall survival (OS) and progression-free survival (PFS). Additional analyses were carried out for molecular subgroups. rs3817198 in LSP1 (lymphocyte-specific protein 1) was the only SNP that significantly influenced OS (p = 0.01) and PFS (p < 0.01) in the likelihood ratio test comparing the genetic survival model with the clinical survival model. In the molecular subgroups, triple-negative patients with two minor alleles in rs3817198 had a much better prognosis relative to OS (adjusted HR 0.03; 95% CI 0.002 - 0.279) and PFS (HR 0.09; 95% CI 0.02 - 0.36) than patients with the common alleles. The same effect on PFS was shown for patients with luminal A tumors (HR 0.19; 95% CI 0.05 - 0.84), whereas patients with luminal B tumors had a poorer PFS with two minor alleles (HR 2.13; 95% CI 1.02 - 4.40). The variant in rs3817198 has a prognostic effect particularly in the subgroup of patients with triple-negative BC, suggesting a possible link with immunomodulation and BC.

PEDF Is Associated with the Termination of Chondrocyte Phenotype and Catabolism of Cartilage Tissue.

Objective. To investigate the expression and target genes of pigment epithelium-derived factor (PEDF) in cartilage and chondrocytes, respectively. Methods. We analyzed the expression pattern of PEDF in different human cartilaginous tissues including articular cartilage, osteophytic cartilage, and fetal epiphyseal and growth plate cartilage, by immunohistochemistry and quantitative real-time (qRT) PCR. Transcriptome analysis after stimulation of human articular chondrocytes with rhPEDF was performed by RNA sequencing (RNA-Seq) and confirmed by qRT-PCR. Results. Immunohistochemically, PEDF could be detected in transient cartilaginous tissue that is prone to undergo endochondral ossification, including epiphyseal cartilage, growth plate cartilage, and osteophytic cartilage. In contrast, PEDF was hardly detected in healthy articular cartilage and in the superficial zone of epiphyses, regions that are characterized by a permanent stable chondrocyte phenotype. RNA-Seq analysis and qRT-PCR demonstrated that rhPEDF significantly induced the expression of a number of matrix-degrading factors including SAA1, MMP1, MMP3, and MMP13. Simultaneously, a number of cartilage-specific genes including COL2A1, COL9A2, COMP, and LECT were among the most significantly downregulated genes. Conclusions. PEDF represents a marker for transient cartilage during all neonatal and postnatal developmental stages and promotes the termination of cartilage tissue by upregulation of matrix-degrading factors and downregulation of cartilage-specific genes. These data provide the basis for novel strategies to stabilize the phenotype of articular cartilage and prevent its degradation.

The effect of Nigella sativa oil on prevention of myringosclerosis in a Guinea pig model.

OBJECTIVES: In this study, our aim was to identify the possible effects of Nigella sativa L. (NS) [blackcumin] seed oil on the prevention of experimentally induced myringosclerosis (MS). MATERIALS AND METHODS: Fourteen Guinea pigs were used and they were divided into three groups. Tympanic membranes (TM) of all animals were perforated and then group I was treated with saline soaked gel foams as a control group, group II was treated with 0.5 ml NS oil soaked gel foams at 0, 24 and 48 h and group III was treated with 5 ml NS oil orally at 0, 24, 48, 72 and 120 h. After 15 days, all animals were euthanized. Tympanic membranes were evaluated macroscopically and histopathologically. RESULTS: Groups I showed extensive myringosclerosis in contrast to those of Groups II and III which had significantly less changes (p < 0.05). The fibrosis and inflammation in the lamina propria of the tympanic membranes of Groups I was found to be significantly more pronounced (p < 0.05). The tympanic membranes were found to be significantly thinner in Groups II and III when compared with Groups I (p < 0.05). CONCLUSIONS: The results of this study suggested that topical or oral administration of NS oil supressed the inflammation and fibroblastic activity in the lamina propria of the myringotomized TMs of the Guinea pigs. For providing further evidence to use plant extracts as antioxidant and antiinflammatory therapy after myringotomy or ventilation tube insertion, further clinical studies with larger population will be essential.

Rhinovirus inhibits IL-17A and the downstream immune responses in allergic asthma.

The proinflammatory cytokine interleukin-17A (IL-17A) is known to mediate antimicrobial activity, but its role during rhinovirus (RV) infections and in asthma needs further investigation. Therefore, we addressed the role of IL-17A during allergic asthma and antiviral immune response in human and murine immunocompetent cells. In this study we found that asthmatic children with a RV infection in their upper airways have upregulated mRNA levels of the antiviral cytokine interferon type I (IFN)-ß and the transcription factor T-box 21 (TBX21) and reduced levels of IL-17A protein in their peripheral blood mononuclear cells (PBMCs). We also found that IL-17A inhibited RV1b replication in infected human lung epithelial cells A549. Furthermore, by using gene array analysis we discovered that targeted deletion of Il17a in murine lung CD4(+) T cells impaired Oas1g mRNA downstream of Ifnß, independently from RV infection. Additionally, in PBMCs of children with a RV infection in their nasalpharyngeal fluid OAS1 gene expression was found downregulated. Finally RV1b inhibited IL-17A production in lung CD4(+) T cells in a setting of experimental asthma. These results indicate that the RV1b inhibits IL-17A in T helper type 17 cells and IL-17A clears RV1b infection in epithelial cells. In both cases IL-17A contributes to fend off RV1b infection by inducing genes downstream of interferon type I pathway.

The effect of Hypericum perforatum L. (St. John's Wort) on prevention of myringosclerosis after myringotomy in a rat model.

OBJECTIVES: The purpose of this study was to identify the possible effects of Hypericum Perforatum (HP) on the prevention of experimentally induced myringosclerosis (MS). METHODS: Twenty eight Wistar Albino rats were used and they were divided into four groups. Tympanic membranes of all animals were perforated and then group I had no treatment as a control group, group II had treated with olive oil only, group III had treated with HP orally and group IV had treated with HP topically. RESULTS: Groups I and II showed extensive myringosclerosis in contrast to those of Groups III and IV which had significantly less changes (p<0.05). The inflammation and fibrosis in the lamina propria of the tympanic membranes of Groups I and II were found to be significantly more pronounced (p<0.05). The tympanic membranes were found to be significantly thinner in Groups III and IV when compared with Groups I and II (p<0.05). CONCLUSIONS: The results of the present study suggested that oral or topical administration of HP extract after myringotomy suppressed the inflammation and fibroblastic activity in the lamina propria of the myringotomized TMs of the rats. Further clinical studies with larger population using HP and other antioxidants will be essential to provide further evidence for use of antioxidant therapy in patients with myringotomy and ventilation tube insertion for otitis media with effusion.

Whole exome sequencing reveals a novel de novo FOXC1 mutation in a patient with unrecognized Axenfeld-Rieger syndrome and glaucoma.

We report the identification of a novel mutation in the fork-head box C1 (FOXC1) gene which occurred de novo in an Italian patient with unrecognized Axenfeld-Rieger syndrome. He was previously diagnosed as having late recognized primary congenital glaucoma at the age of 14 years and was subsequently subjected to multiple surgical interventions due to uncontrolled intraocular pressure and progressive visual field loss. After exclusion of mutations in CYP1B1 and MYOC, trio-whole-exome sequencing revealed de novo in frame deletion in the coding region of the FOXC1 gene (c.407_409delGTC, p.V137del) leading to a deletion of the evolutionary conserved amino acid Valine at position 137 of the protein. Molecular modeling predicted that Val137 deletion impairs FOXC1 DNA-binding capacity and transcriptional activation. Since loss-of-function mutations in FOXC1 are associated with Axenfeld-Rieger syndrome, the genetic findings in combination with re-evaluation of the patient's clinical data resulted in a corrected diagnosis of Axenfeld-Rieger syndrome with developmental glaucoma. We therefore suggest that in addition to CYP1B1 and MYOC, FOXC1 should be included in the genetic analysis of cases with unclear glaucomatous phenotypes to ensure proper diagnosis, adequate treatment and appropriate genetic counseling.

Anticancer use of nanoparticles as nucleic acid carriers.

Advances in nanotechnology opened up new horizons in the field of cancer research. Nanoparticles made of various organic and inorganic materials and with different optical, magnetic and physical characteristics have the potential to revolutionize the way we diagnose, treat and follow-up cancers. Importantly, designs that might allow tumor-specific targeting and lesser side effects may be produced. Nanoparticles may be tailored to carry conventional chemotherapeutics or new generation organic drugs. Currently, most of the drugs that are commonly used, are small chemical molecules targeting disease-related enzymes. Recent progress in RNA interference technologies showed that, even proteins that are considered to be "undruggable" by small chemical molecules, might be targeted by small RNAs for the purpose of curing diseases, including cancer. In fact, small RNAs such as siRNAs, shRNAs and miRNAs can drastically change cellular levels of almost any given disease-associated protein or protein group, resulting in a therapeutic effect. Gene therapy attempts were failing mainly due to delivery viral vector-related side effects. Biocompatible, non-toxic and efficient nanoparticle carriers raise new hopes for the gene therapy of cancer. In this review article, we discuss new advances in nucleic acid and especially RNA carrier nanoparticles, and summarize recent progress about their use in cancer therapy.

Biodegradable annuloplasty ring two years after implantation: first histological demonstration in human mitral annulus.

Although biodegradable annuloplasty rings have been used in clinics for almost a decade for mitral and/or tricuspid annuloplasty, the fate of the ring at the histological level has not been demonstrated in humans to date. The mitral annulus of a 39-year-old patient who underwent heart transplantation almost two years after annuloplasty was subjected to histological evaluation to demonstrate the mitral annular structures and consequences of biodegradable ring annuloplasty. On examination, the ring was shown to have completely degraded, and a fibrous band had formed in the posterior mitral annulus. No signs of residual calcification were observed. Neighboring structures such as circumflex artery and the great cardiac vein were intact. It can be concluded that the biodegradable annuloplasty ring is completely degraded in humans after implantation, leaving a fibrous band behind to support the posterior annulus. The risk of circumflex artery and great cardiac vein injury may not be considerable if the correct implantation technique is used.