Lateral pharyngoplasty vs. traditional uvulopalatopharyngoplasty for patients with OSA: systematic review and meta-analysis.

OBJECTIVES: To compare the efficacy and success rates of lateral pharyngoplasty techniques (LP) vs. uvulopalatopharyngoplasty (UPPP) among adult patients surgically treated for obstructive sleep apnea. METHODS: A systematic literature review of the last 20 years' papers was conducted using PubMed/Medline, Embase, Web of Science, Scholar, and the Cochrane Library until April 2021. Only full-text English articles comparing LP and UPPP outcomes in adult patients with objective outcomes were included in the study. RESULTS: We included 9 articles for a total of 312 surgically treated patients with OSA. LP techniques for obstructive sleep apnea were used on 186 (60%) subjects, while 126 patients (40%) were treated with UPPP. Both surgical procedures resulted in significant improvements in apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS) score, and lowest oxygen saturation (LOS) (p < 0.001 in all cases). Although better outcomes were reported with lateral pharyngoplasty, the differences were not significant compared to UPPP post-operative results (p > 0.05 in all cases). CONCLUSIONS: UPPP and LP are both effective surgical procedures in treating OSA in adults. Although not significant, LPs demonstrated improved post-operative outcomes. However, further evidence comparing the surgical effect on patients with OSA is needed to discriminate post-operative outcomes.

Green tea catechins can bind and modify ERp57/PDIA3 activity.

BACKGROUND: Green tea is a rich source of polyphenols, mainly catechins (flavanols), which significantly contribute to the beneficial health effects of green tea in the prevention and treatment of various diseases. In this study the effects of four green tea catechins on protein ERp57, also known as protein disulfide isomerase isoform A3 (PDIA3), have been investigated in an in vitro model. METHODS: The interaction of catechins with ERp57 was explored by fluorescence quenching and surface plasmon resonance techniques and their effect on ERp57 activities was investigated. RESULTS: A higher affinity was observed for galloylated cathechins, which bind close to the thioredoxin-like redox-sensitive active sites of the protein, with a preference for the oxidized form. The effects of these catechins on ERp57 properties were also investigated and a moderate inhibition of the reductase activity of ERp57 was observed as well as a strong inhibition of ERp57 DNA binding activity. CONCLUSIONS: Considering the high affinity of galloylated catechins for ERp57 and their capability to inhibit ERp57 binding to other macromolecular ligands, some effects of catechins interaction with this protein on eukaryotic cells may be expected. GENERAL SIGNIFICANCE: This study provides information to better understand the molecular mechanisms underlying the biological activities of catechins and to design new polyphenol-based ERp57-specific inhibitors.

Detection of serum IgA to HSV1 and its diagnostic role in sudden hearing loss.

A viral etiology of sudden hearing loss has been hypothesized by many authors. HSV1 neurotropism and its involvement in sudden hearing loss has implicated HSV1 as one of the most accredited etiological agents. A non-invasive method such as the titration of HSV1-specific IgA was evaluated to determine the role of HSV1 as a possible cause sudden hearing loss. A prospective study was carried out by titration of serum IgA to HSV1 in 93 patients and in a control group of 50 healthy subjects and 35 subjects suffering from recent herpes labialis reactivation. Statistical analysis of the results disclosed that IgA titers to HSV1 higher than 1:80 are suggestive for the association of HSV1 infection and sudden hearing loss. Moreover, acyclovir therapy was effective in 81% of patients who showed high specific IgA titers. Overall, the titration of specific serum IgA to HSV1 can be a useful tool to determine the viral etiology of certain cases of sudden hearing loss. This method is simple to perform and minimally invasive. It can lead to a rapid presumptive diagnosis and to prompt specific therapy, reducing the need for corticosteroids.

Nanomolar melatonin enhances nNOS expression and controls HaCaT-cells bioenergetics.

A novel role of melatonin was unveiled, using immortalized human keratinocyte cells (HaCaT) as a model system. Within a time window compatible with its circadian rhythm, melatonin at nanomolar concentration raised both the expression level of the neuronal nitric oxide synthase mRNA and the nitric oxide oxidation products, nitrite and nitrate. On the same time scale, a depression of the mitochondrial membrane potential was detected together with a decrease of the oxidative phosphorylation efficiency, compensated by glycolysis as testified by an increased production of lactate. The melatonin concentration, ∼ nmolar, inducing the bioenergetic effects and their time dependence, both suggest that the observed nitric oxide-induced mitochondrial changes might play a role in the metabolic pathways characterizing the circadian melatonin chemistry.

Computational Analyses of YY1 and Its Target RKIP Reveal Their Diagnostic and Prognostic Roles in Lung Cancer.

Lung cancer (LC) represents a global threat, being the tumor with the highest mortality rate. Despite the introduction of novel therapies (e.g., targeted inhibitors, immune-checkpoint inhibitors), relapses are still very frequent. Accordingly, there is an urgent need for reliable predictive biomarkers and therapeutically druggable targets. Yin-Yang 1 (YY1) is a transcription factor that may work either as an oncogene or a tumor suppressor, depending on the genotype and the phenotype of the tumor. The Raf Kinase Inhibitory Protein (RKIP), is a tumor suppressor and immune enhancer often found downregulated in the majority of the examined cancers. In the present report, the role of both YY1 and RKIP in LC is thoroughly explored through the analysis of several deposited RNA and protein expression datasets. The computational analyses revealed that YY1 negatively regulates RKIP expression in LC, as corroborated by the deposited YY1-ChIP-Seq experiments and validated by their robust negative correlation. Additionally, YY1 expression is significantly higher in LC samples compared to normal matching ones, whereas RKIP expression is lower in LC and high in normal matching tissues. These observed differences, unlike many current biomarkers, bear a diagnostic significance, as proven by the ROC analyses. Finally, the survival data support the notion that both YY1 and RKIP might represent strong prognostic biomarkers. Overall, the reported findings indicate that YY1 and RKIP expression levels may play a role in LC as potential biomarkers and therapeutic targets. However, further studies will be necessary to validate the in silico results.

ERp57/GRP58: a protein with multiple functions.

The protein ERp57/GRP58 is a stress-responsive protein and a component of the protein disulfide isomerase family. Its functions in the endoplasmic reticulum are well known, concerning mainly the proper folding and quality control of glycoproteins, and participation in the assembly of the major histocompatibility complex class 1. However, ERp57 is present in many other subcellular locations, where it is involved in a variety of functions, primarily suggested by its participation in complexes with other proteins and even with DNA. While in some instances these roles need to be confirmed by further studies, a great number of observations support the participation of ERp57 in signal transduction from the cell surface, in regulatory processes taking place in the nucleus, and in multimeric protein complexes involved in DNA repair.

Effects of hormone therapy containing 2 mg drospirenone and 1 mg 17ß-estradiol on postmenopausal exacerbation of Meniere's disease: Preliminary study.

The present study aimed to evaluate the effects of 2 mg drospirenone (DRSP) and 1 mg 17ß-estradiol (E2) hormone therapy (HT) in combination with rehabilitation therapy for postmenopausal women with Meniere's disease (MD). The combined drug hormone treatment was denoted as DRSP/E2. A total of 65 postmenopausal female patients with MD and severe distress were enrolled in the present prospective study. A total of 31 women comprised the study group (group A), undergoing HT and rehabilitation therapy, whereas 34 women who opted for rehabilitation therapy alone comprised the control group (group B). Vestibular function and distress associated with MD were assessed by stabilometry and the Dizziness Handicap Inventory (DHI) questionnaire, respectively. The data were collected at baseline and during the 3- and 6-month follow-up visits. The areas of the stabilometric ellipses exhibited a higher reduction in group A compared with group B with regard to the baseline values at both follow-up assessments (P<0.001). At baseline, both groups exhibited severe self-perceived discomfort, with similar DHI scores of 72.3±3.7 (group A) and 70.6±3.9 (group B; P=0.07). At the 3-month follow-up, both groups underwent a gradual improvement, which was significantly higher in group A (47.5±3.7) compared with in group B (64.2±3.3; P<0.001). At the 6-month follow-up, the DHI scores were improved in group A (43.4±3.4) compared with in group B (58.5±3.1; P<0.001). Therefore, DRSP/E2 HT was effective in reducing the fluid overload, which is characteristic of MD. The findings of the present study demonstrated that integrated therapy based on the administration of DRSP/E2 HT and rehabilitation may be more effective compared with rehabilitation alone for the management of postmenopausal exacerbation of MD.

Quality of Life After Total LaryngectomyVoice-Related Quality of Life After Total Laryngectomy: Systematic Review and Meta-Analysis.

BACKGROUND: To compare voice rehabilitation-related quality of life among patients surgically treated for total laryngectomy and rehabilitated with esophageal (EV) and tracheoesophageal (TEV) voice. METHODS: A systematic literature review of articles from the past 20 years was conducted, and only full-text English articles comparing VTE and EV results in laryngectomized patients were included. RESULTS: We provided 15 articles for a total of 1085 laryngectomized patients undergoing voice rehabilitation, of which 869 (80.1%) were treated with voice prosthesis while 216 (19.9%) to esophageal speech. Pooled VHI outcomes showed a significantly better score for the TEV group than EV one (31.93±12.11 versus 35.39±20.6; P = 0.003), but no significant difference was recorded at VrQoL (8.27±5.98 versus 9.27±2.02; P = 0.19). CONCLUSION: TEV and EV are both effective procedures in voice rehabilitation after laryngectomy. Although TEV allows for significantly better speech performance, it does not necessarily correlate with a high VrQoL.

Role of ERp57 in the signaling and transcriptional activity of STAT3 in a melanoma cell line.

Chromatin immunoprecipitation in M14 melanoma cells showed that the protein ERp57 (endoplasmic reticulum protein 57) binds to DNA in the proximity of STAT3 in a subset of STAT3-regulated genes. In the same cells, IL-6 induced a significant increase of the expression of one of these genes, i.e. CRP. Upon depletion of ERp57 by RNA interference, the phosphorylation of STAT3 on tyrosine 705 was decreased, and the IL-6-induced activation of CRP expression was completely suppressed. In vitro experiments showed that ERp57 is also required for the binding of STAT3 to its consensus sequence on DNA. Thus ERp57, previously shown to associate with STAT3 in the cytosol and in the nuclear STAT3-containing enhanceosome, is a necessary cofactor for the regulation of at least a subset of STAT3-dependent genes, probably intervening both at the site of STAT3 phosphorylation and at the nuclear level.

Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach.

BACKGROUND: The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS), which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes. RESULTS: The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized. CONCLUSIONS: Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional) proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis.

Cancer Management during COVID-19 Pandemic: Is Immune Checkpoint Inhibitors-Based Immunotherapy Harmful or Beneficial?

The coronavirus disease 2019 (COVID-19) is currently representing a global health threat especially for fragile individuals, such as cancer patients. It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. The consequences of this pandemic for oncology are really heavy, as the entire healthcare system got reorganized. Both oncologists and cancer patients are experiencing rescheduling of treatments and disruptions of appointments with a concurrent surge of fear and stress. In this review all the up-to-date findings, concerning the association between COVID-19 and cancer, are reported. A remaining very debated question regards the use of an innovative class of anti-cancer molecules, the immune checkpoint inhibitors (ICIs), given their modulating effects on the immune system. For that reason, administration of ICIs to cancer patients represents a question mark during this pandemic, as its correlation with COVID-19-associated risks is still under investigation. Based on the mechanisms of action of ICIs and the current evidence, we suggest that ICIs not only can be safely administered to cancer patients, but they might even be beneficial in COVID-19-positive cancer patients, by exerting an immune-stimulating action.

Evaluation of an improved small gauge needle for venipuncture in children with difficult venous access: Impact on sample quality, phlebotomist satisfaction and patient pain perception.

BACKGROUND: Smaller needles gauge (G) may reduce pain and improve vein access in difficult venous access (DVA). Aims were to compare the performances of two Beckton-Dickinson (BD) Vacutainer® Blood Collection Sets in a pediatric setting: UltraTouch™ Push Button (UT-PBBCS) and Safety-Lok™ (SLBCS). MATERIALS AND METHODS: Questionnaires were used to record venipuncture features, patient pain perception and phlebotomist difficulty score. Specimen quality was evaluated by hemolysis index (HI) on Roche Cobas® 6000. RESULTS: SLBCS (21/23G) or UT-PBBCS (23/25G) were used in 211 (50.2%) and 209 (49.8%) subjects. Pain was associated with age (p < 0.0001) and was lower in UT-PBBCS (p = 0.0339). Difficulty was significantly associated with age (p = 0.002), not with needle gauge (p = 0.461) and it was 0.42 points lower in UT-PBBCS. HI was not associated with blood collection set (p = 0.385). CONCLUSIONS: UT-PBBCS globally performed better than SLBCS and could enhance phlebotomy and patient comfort, without affecting sample quality in pediatric patients with DVA.

Droplet digital PCR for the detection and monitoring of Legionella pneumophila.

Legionella pneumophila (L. pneumophila) is a harmful pathogen often found in water systems. In hospitals, the absence of L. pneumophila in water systems is mandatory by law, therefore, frequent and effective monitoring of water is of fundamental importance. Molecular methods based on reverse transcription­quantitative polymerase chain reaction (RT­qPCR) have been proposed for the detection of L. pneumophila, however, the sensitivity and accuracy of these methods have not been validated yet. Therefore, it is important to evaluate other strategies able to overcome the limits of culture­based and RT­qPCR methods. On these bases, we compared the sensitivity and accuracy of droplet digital PCR (ddPCR) and RT­qPCR in water samples with known concentrations of L. pneumophila and in an in vitro model of water heat treatments. ddPCR showed a higher sensitivity rate and accuracy compared to RT­qPCR in detecting low bacterial load. In addition, ddPCR is not affected by the presence of fragmented DNA and showed higher accuracy than RT­qPCR in monitoring the efficacy of heat shock treatments. In conclusion, ddPCR represents an innovative strategy to effectively detect L. pneumophila in water samples. Thanks to its high robustness, ddPCR could be applied also for the detection of L. pneumophila in patients with suspected legionellosis.

Droplet Digital PCR Analysis of Liquid Biopsy Samples Unveils the Diagnostic Role of hsa-miR-133a-3p and hsa-miR-375-3p in Oral Cancer.

Despite the availability of screening programs, oral cancer deaths are increasing due to the lack of diagnostic biomarkers leading to late diagnosis and a poor prognosis. Therefore, there is an urgent need to discover novel effective biomarkers for this tumor. On these bases, the aim of this study was to validate the diagnostic potential of microRNAs (miRNAs) through the analysis of liquid biopsy samples obtained from ten oral cancer patients and ten healthy controls. The expression of four selected miRNAs was evaluated by using droplet digital PCR (ddPCR) in a pilot cohort of ten oral cancer patients and ten healthy donors. Bioinformatics analyses were performed to assess the functional role of these miRNAs. The expression levels of the predicted down-regulated hsa-miR-133a-3p and hsa-miR-375-3p were significantly reduced in oral cancer patients compared to normal individuals while no significant results were obtained for the up-regulated hsa-miR-503-5p and hsa-miR-196a-5p. ROC analysis confirmed the high sensitivity and specificity of hsa-miR-375-3p and hsa-miR-133a-3p. Therefore, both miRNAs are significantly down-regulated in cancer patients and can be used as biomarkers for the early diagnosis of oral cancer. The analysis of circulating miRNAs in a larger series of patients is mandatory to confirm the results obtained in this pilot study.

Influence of cigarette smoking on allergic rhinitis: a comparative study on smokers and non-smokers.

It has been described that exposure to tobacco smoke causes worsening of allergic rhinitis symptoms. Otherwise, some studies have demonstrated a negative association between cigarette smoke and allergic rhinitis (AR). Given this inconsistency, this study evaluated the quality of life and immuno-inflammatory parameters in current smokers and nonsmokers suffering from AR. A comparative cross-sectional study was conducted in patients who presented symptoms of AR. Patients were categorized into two groups: current smokers and non-smokers based on salivary cotinine measurements. Primary outcomes were the levels of immuno-inflammatory biomarkers (IgE, IL-4, IL-5, IL-13, IL-17, and IL-33) in serum and nasal lavage and the quality of life assessed by the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ). Secondary outcomes included salivary cotinine levels, and pulmonary function parameters, such as forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), and FEV1/FVC ratio. Twenty-two patients per group were included in the analysis, with no significant difference regarding demographic characteristics. Statistically significant higher values in salivary cotinine levels (p<0.001) and lower lung function FEV1 (p=0.044) and FEV1/FVC (p=0.047) were found in smokers than in nonsmokers. Only serum IL-33 was significantly different in the 2 groups (p<0.001): smokers had higher values compared to non-smokers. There were no significant differences in MiniRQLQ parameters. Although cigarette smoking was not associated with more severe symptoms, smoking could be associated with increased risk of developing airway remodeling and decreased lung function in AR patients, thus appropriate treatment should be prescribed if smoke avoidance is unfeasible.

DNA damage and repair: from molecular mechanisms to health implications.

DNA is subjected to several modifications, resulting from endogenous and exogenous sources. The cell has developed a network of complementary DNA-repair mechanisms, and in the human genome, >130 genes have been found to be involved. Knowledge about the basic mechanisms for DNA repair has revealed an unexpected complexity, with overlapping specificity within the same pathway, as well as extensive functional interactions between proteins involved in repair pathways. Unrepaired or improperly repaired DNA lesions have serious potential consequences for the cell, leading to genomic instability and deregulation of cellular functions. A number of disorders or syndromes, including several cancer predispositions and accelerated aging, are linked to an inherited defect in one of the DNA-repair pathways. Genomic instability, a characteristic of most human malignancies, can also arise from acquired defects in DNA repair, and the specific pathway affected is predictive of types of mutations, tumor drug sensitivity, and treatment outcome. Although DNA repair has received little attention as a determinant of drug sensitivity, emerging knowledge of mutations and polymorphisms in key human DNA-repair genes may provide a rational basis for improved strategies for therapeutic interventions on a number of tumors and degenerative disorders.

Endogenous reverse transcriptase as a mediator of ursolic acid's anti-proliferative and differentiating effects in human cancer cell lines.

Ursolic acid (UA) is a pentacyclic triterpenoid compound that is widely distributed in the plant kingdom and has a broad range of biological effects. Here, we examined the effects of UA on the proliferation and differentiation of human tumor cell lines from melanoma (A375), glioblastoma (U87) and thyroid anaplastic carcinoma (ARO), and on the proliferation of a non-transformed human fibroblast cell line (WI-38). The results show that UA inhibits tumor cell proliferation in a dose- and time-dependent manner. Consistent with this finding, UA treatment promotes differentiation of all of the analyzed tumor cell lines. Interestingly, we found that UA inhibits the endogenous reverse transcriptase (RT) activity in tumor cells, which has recently been shown to be involved in the control of proliferation and differentiation of neoplastic cells. Considering these findings, we suggest that the observed anti-proliferative and differentiating effects of UA may be related to this target.

The binding of antibiotics to ERp57/GRP58.

The effects of five antibiotics, previously described as ligands of protein disulfide isomerase PDI, have now been studied on the homologous protein ERp57. They bind to this protein with much higher affinity than to PDI, and some of them inhibit the reductase and the DNA-binding activities of ERp57. In view of the high affinity of vancomycin, erythromycin and streptomycin, some effects of their interaction with this protein might be expected in vivo.

Effects of combined oral contraception containing drospirenone on premenstrual exacerbation of Meniere's disease: Preliminary study.

OBJECTIVES: Meniere's disease is caused by an augmented endolymph pressure in the inner ear; symptoms are vertigo, fluctuating hearing loss and tinnitus. Exacerbations has been noted during premenstrual phase. The study aims to evaluate the effects of a 20 µm Ethinylestradiol (EE) and 3 mg Drospirenone (DRSP) oral contraceptive (20 µmEE/3mgDRSP) in continuous regimen, associated with rehabilitation therapy on Meniere's disease. STUDY DESIGN: This non-randomized controlled study was performed from October 2015 to October 2017. Forty-two premenopausal women affected by MD with severe distress in the premenstrual phase were enrolled. Sixteen women constituted the study group (Group A), and twenty women constituted the control group (Group B). Group A underwent EE/DRSP therapy and rehabilitation and Group B underwent rehabilitation therapy alone. Stabilometry and the Dizziness Handicap Inventory questionnaire were used to measure vestibular function and distress related to the disease, respectively, at baseline (T0), 3 months (T1) and 6 months (T2). RESULTS: At T0, both groups had large, similar areas of stabilometric ellipses (p = NS) that reduced more in Group A than in Group B, at T1 and T2 (p < 0.001). High scores of the DHI (cut-off ≤54) were observed at T0 in both groups (A 66.8 ±â€¯2.8 vs B 65.5 ±â€¯3.6; p = NS). At T1, a gradual improvement in both groups was observed, manly in Group A (A 45.1 ±â€¯3.6 vs B 62.4 ±â€¯4.1; p < 0.001). At T2, the DHI scores were significantly lower in Group A (39.2 ±â€¯3.8) compared to Group B (68.8 ±â€¯3.6) (p < 0.001). CONCLUSIONS: DRSP could be effective in reducing the fluid overload typical of the premenstrual phase, improving symptoms of MD. The results support the efficacy of EE/DRSP usage associated with rehabilitation therapy on premenstrual exacerbation of MD.

Relationship between sleeping difficulties and airway symptoms severity with the health-related quality of life in patients with GERD.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a chronic disease highly associated with several pulmonary disease and sleep disorders leading to a negative impact on the quality of life. Aim of this study was to investigate the correlation between these disorders and the health-related quality of life. METHODS: Patients were recruited from the Department of Medical Sciences, Surgical and Advanced Technologies, GF Ingrassia, University of Catania, from October 2015 to May 2016. Enrolled patients were classified by different symptomology severity presentation according to the Reflux, Airway and Sleep Questionnaire (RASQ). General data, modified GERD impact scores and the 36-Item Short Form (SF-36) questionnaire scores of these patients were analyzed. RESULTS: A total of 173 patients were included into the study. Patients with moderate severity of airway symptoms had a significant lower SF-36 scores than those with mild severity. Patients with advanced sleeping difficulties severity owned the lowest scores among all cases. The impact to the daily activity of each affected individuals had a positive association with the severity of airway and sleeping disorders. CONCLUSIONS: The severity of these reflux-related disorders is well correlated with a significant negative impact on the normal daily activity. The cases with advanced severity of sleeping difficulties had the worst well-being.