Orofacial muscles activity in children with swallowing dysfunction and removable functional appliances

Swallowing dysfunction is a frequent disorder among children and refers to an altered tongue posture and abnormal tongue movement during swallowing. Removable functional appliance is one of the treatments applied by dentistry to correct this disorder. The aim of this study was to evaluate any differences on orofacial muscles activity in children with swallowing dysfunction with and without removable functional appliances. 68 children were eligible for the study and divided into the orthodontic group (OG) and the no-orthodontic group (NO-OG). Both groups performed a dental occlusion-class evaluation, a swallowing function test and a myoscan analysis in order to measure perioral forces (i.e. tongue extension force, lip pressure, masseter contraction force). Our results showed a significant difference (P=0.02) between OG and NO-OG for the tongue extension force, whereas no significant differences (P>0.05) were found for the other parameters. Our findings suggest that children with swallowing dysfunction and removable functional appliance show orofacial muscles activity within the range of reference values (except for the lip pressure). However, we hypothesize that orthodontic treatment can achieve more effective results with integration of myofunctional therapy

Sudden sensorineural hearing loss: is there a relationship between routine haematological parameters and audiogram shapes?

Objective: To investigate the relationship between haematological routine parameters and audiogram shapes in patients affected by sudden sensorineural hearing loss (SSNHL). Design: A retrospective study. All patients were divided into four groups according to the audiometric curve and mean values of haematological parameters (haemoglobin, white blood cell, neutrophils and lymphocytes relative count, platelet count, haematocrit, prothrombin time, activated partial thromboplastin time, fibrinogen and neutrophil-to-lymphocite ratio) of each group were statistically compared. The prognostic role of blood profile and coagulation test was also examined. Study sample: A cohort of 183 SSNHL patients without comorbidities. Results: With a 48.78% of complete hearing recovery, individuals affected by upsloping hearing loss presented a better prognosis instead of flat (18.36%), downsloping (19.23%) and anacusis (2.45%) groups (p = 0.0001). The multivariate analysis of complete blood count values revealed lower mean percentage of lymphocytes (p = 0.041) and higher platelet levels (p = 0.015) in case of downsloping hearing loss; with the exception of fibrinogen (p = 0.041), none of the main haematological parameters studied resulted associated with poorer prognosis. Conclusions: Our work suggested a lack of association between haematological parameters and a defined audiometric picture in SSNHL patients; furthermore, only fibrinogen seems to influence the prognosis of this disease

The analysis of the expression pattern of the intracellular and extracellular miRNAs in prostate tumor cell lines exposed to cytotoxic drugs.

It has been recently discovered that microRNAs are stably expressed in body fluids of several organisms and that the expression patterns in the plasma/serum of cancer patients could represent a diagnostic/predictive tool of the disease. Extracellular miRNAs have been also found in the growth medium of cells in culture and this prompted us to verify whether prostate tumor cell lines release miRNAs specific of prostate tumor patients and whether anticancer drugs affect the expression patterns of the extracellular miRNAs. First of all we determined the expression of either prostate specific (PS-miRNA) or non prostate specific (NPS-miRNA) miRNAs in the growth medium of PC3 and DU-145 cells (prostate metastatic tumor cell lines) in comparison to PNT1A (immortalized prostate cell line). We found that the levels of both the intracellular and extracellular PS-miRNAs were higher in PC3 and DU-145 tumor cell lines in comparison to the immortalized cell line PNT1A and that a positive correlation exists between the intracellular and the extracellular levels suggesting that the release of miRNA in the growth medium may be a manner to maintain the intracellular miRNAs at physiological level. Thereafter, we investigated whether the release of miRNAs is affected in cells upon their exposure to a cytotoxic drug. To address the point, PC-3 and DU-145 cells were exposed to a cytotoxic concentration of either fludarabine (10 μg/mL) or taxotere (30 nM) for 48 hours. At the end of the treatment both the intracellular and extracellular PS-miRNAs and NPS-miRNAs were quantified. Data showed that i) those miRNAs that were up regulated in cells surviving to either fludarabine or taxotere were not released and that ii) the up regulated miRNAs found in fludarabine-or in taxotere-surviving cells were not the same. Overall data indicate for the first time a possible involvement of miRNAs in the survival/resistance of tumor cells to cytotoxic drugs and suggest that the expression pattern of the intracellular and extracellular miRNAs could be an useful tool to identify in tumor cell lines miRNAs responsible of survival/resistance to cytotoxic drugs and in plasma/serum of cancer patients the efficacy of an anticancer treatment

The RNA Activator ds-p21 Potentiates the Cytotoxicity Induced by Fludarabine in Dohh2 Cells

Recently, it has been reported that, in several tumor cell lines, short double-stranded RNAs tailored for promoter regions of specific genes are able to activate their transcription. Such molecules (named RNA activators) act opposite to other double-stranded RNA molecules (named RNA inhibitors) in that the overexpression instead of underexpression of a given gene is triggered. In Dohh2 non-Hodgkin lymphoma cells, the transcriptional repressor BCL6, which negatively controls both p53 and p21, is overexpressed, so that the cells can escape the check point governed by p53 and proliferate. The aim of this work was to investigate whether the RNA activator p21 can represent a tool to circumvent the transcriptional control of BCL6 and induce the blockage of cell proliferation in Dohh2 non-Hodgkin lymphoma cells. For that, Dohh2 cells were transfected with either a control RNA activator (ds-NC) or an RNA activator specific for human p21 promoter (ds-p21). At various time points after transfection, the cells were collected and p21 was measured. Dohh2 cells transfected with ds-p21 showed a slight but significant overexpression of p21 at both mRNA and protein levels. Nonetheless, cell proliferation, cell cycle, and apoptosis were not significantly modified. In contrast, the exposure of Dohh2 cells transfected with ds-p21 to fludarabine potentiates the cytotoxicity of the drug, suggesting the RNA activator p21 complements the fludarabine-dependent cell death pathways

Audiologic profile of OSAS and simple snoring patients: the effect of chronic nocturnal intermittent hypoxia on auditory function

The objective of this work was to study the effect of nocturnal intermittent hypoxia on auditory function of simple snoring patients and subjects affected by OSAS; we compared the audiologic profile with the severity of OSAS to detect early signs of cochlear damage. One hundred-sixty patients underwent overnight polysomnography, micro-otoscopy, multi-frequency audiometry, acufenometry, TEOAE recording and d-ROMs test. All subjects were divided in four groups, based on presence/absence of AHI (simple snoring without OSAS, mild OSAS, moderate OSAS, severe OSAS). Sixty (37.5 %) patients were not affected by OSAS, 58 (36.25 %) presented a mild OSAS, 18 (11.25 %) a moderate OSAS and 24 (15 %) a severe OSAS; the 57.14 % of moderate to severe OSAS suffered from tinnitus with respect to the 31.03 % of mild OSAS (P = 0.024). A higher percentage (41.66 %) of hearing loss was found among individuals with moderate to severe degree of OSAS (P < 0.0001). All groups were characterized by a mean hearing threshold <25 dB HL for 0.25–3 kHz frequencies and a progressive decrease in hearing sensitivity, particularly for 6–16 kHz frequencies (P < 0.05). The analysis of otoacoustic emissions SNR mean values evidenced a significant difference between simple snoring and severe OSAS individuals for 3 and 4 kHz frequencies (P < 0.05). d-ROM levels resulted higher in patients with severe OSAS with respect to simple snoring subjects (P = 0.004). Our data underline the key role of chronic nocturnal intermittent hypoxia in the development of an early cochlear damage and a more marked high-frequency hearing loss in case of severe OSAS (P < 0.05)

Cognitive Health of Nonagenarians in Southern Italy: A Descriptive Analysis from a Cross-Sectional, Home-Based Pilot Study of Exceptional Longevity (Cilento Initiative on Aging Outcomes Or CIAO).

Background: Nonagenarians and centenarians (NCs) are an extremely fragile population, particularly in regard to their physical and cognitive function. The aim of this study was to define the neurocognitive profiles among 29 NCs and their 49 younger cohabitants aged 50-75 years from The Cilento Initiative on Aging Outcomes (CIAO) Pilot study in the South of Italy that had provided initial hypotheses regarding positive psychological traits related to exceptional longevity. Methods: During the home visits, lifestyle information with specific questionnaires, functional autonomy and the neuropsychological Mini Mental Scale Examination (MMSE), and the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) scale were obtained by qualified study personnel. The total blood oxidative capacity was also determined by testing the reactive derivative of oxygen metabolites (d-ROM) and by the Biological Antioxidant Potential (BAP). In all individuals, the APOE genotype determination was also performed. Results: All the subjects in both groups showed high adherence to the Mediterranean Diet. None of the NCs had severe cognitive impairment, and a very low incidence of dementia was found. The data obtained on the Activities ed Instrumental Activities of Daily Living (ADL-IADL) scale showed that the majority of NCs (16/29) were autonomous in daily life activities. The comparative assessment of NCs and cohabitants showed no significant differences in the laboratory assessment of oxidative stress and APOE genotype. Conclusion: In the Cilento Region of Southern Italy, NCs seemed to have good cognitive status when compared to younger cohabitants aging 50-65 years without significant differences in oxidative stress markers or APOE genotype. These results might be related to optimal adherence to the Mediterranean diet, although other lifestyle factors and positive personality traits may also contribute to their healthy aging. Further studies on a larger population should be performed to confirm the results of this pilot study

Development of an Enriched Polyphenol (Natural Antioxidant) Extract from Orange Juice (Citrus sinensis) by Adsorption on Macroporous Resins

Orange (Citrus sinensis) juice contains a high amount of antioxidant compounds, such as polyphenols and vitamins. The aim of this work was to develop an adsorption procedure for the quantitative recovery of polyphenols from fresh orange juice. Different macroporous resins have been selected to evaluate their affinity for phenolic compound in order to purify the antioxidant compounds from the orange juice. The main compounds of orange juice were firstly characterized using an UPLC-UV-HRMS to define the metabolite profile, and subsequently three different types of adsorbent (XAD-2, XAD-4, and XAD-16N) were tested to concentrate these bioactive compounds. The time of contact was selected based on kinetic studies, and subsequently the adsorption and elution conditions were optimized in order to maximize the recovery of phenolic compounds to obtain an extract rich of bioactive compounds. Lastly, antioxidant capacity of the orange juice extract of selected macroporous resin, obtained under optimized conditions, was determined by in vitro antioxidant assays

The Immunohistochemical Loss of H3K27me3 in Intracranial Meningiomas Predicts Shorter Progression-Free Survival after Stereotactic Radiosurgery

The immunohistochemical loss of histone H3 trimethylated in lysine 27 (H3K27me3) was recently shown to predict recurrence of meningiomas after surgery. However, its association with tumor progression after stereotactic radiosurgery (SRS) is unexplored. To investigate whether H3K27 methylation status may predict progression-free survival (PFS) after SRS, we assessed H3K27me3 immunoexpression in thirty-nine treatment naïve, intracranial, meningiomas, treated with surgery and subsequent SRS for residual (twenty-three cases) or recurrent (sixteen cases) disease. H3K27me3 immunostaining was lost in seven meningiomas, retained in twenty-seven and inconclusive in five. Six of the seven meningiomas (86%) with H3K27me3 loss had tumor progression after SRS, compared to nine of twenty-seven (33%) with H3K27me3 retention (p = 0.0143). In addition, patients harboring a meningioma with H3K27me3 loss had significantly shorter PFS after SRS (range: 10-81 months; median: 34 months), compared to patients featuring a meningioma with retained H3K27me3 (range: 9-143 months; median: 62 months) (p = 0.0036). Nonetheless, tumor sagittal location was the only significant prognostic variable at multivariate analysis for PFS after SRS (p = 0.0142). These findings suggest a previously unreported role of H3K27me3 as a predictor of meningioma progression after SRS for recurrent or residual disease. Modulation of H3K27 methylation status may represent a novel therapeutic strategy to induce radiosensitization of meningiomas

Separase prevents genomic instability by controlling replication fork speed

Proper chromosome segregation is crucial for preserving genomic integrity, and errors in this process cause chromosome mis-segregation, which may contribute to cancer development. Sister chromatid separation is triggered by Separase, an evolutionary conserved protease that cleaves the cohesin complex, allowing the dissolution of sister chromatid cohesion. Here we provide evidence that Separase participates in genomic stability maintenance by controlling replication fork speed. We found that Separase interacted with the replication licensing factors MCM2-7, and genome-wide data showed that Separase co-localized with MCM complex and cohesin. Unexpectedly, the depletion of Separase increased the fork velocity about 1.5-fold and caused a strong acetylation of cohesin's SMC3 subunit and altered checkpoint response. Notably, Separase silencing triggered genomic instability in both HeLa and human primary fibroblast cells. Our results show a novel mechanism for fork progression mediated by Separase and thus the basis for genomic instability associated with tumorigenesis

Separase prevents genomic instability by controlling replication fork speed

Proper chromosome segregation is crucial for preserving genomic integrity, and errors in this process cause chromosome mis-segregation, which may contribute to cancer development. Sister chromatid separation is triggered by Separase, an evolutionary conserved protease that cleaves the cohesin complex, allowing the dissolution of sister chromatid cohesion. Here we provide evidence that Separase participates in genomic stability maintenance by controlling replication fork speed. We found that Separase interacted with the replication licensing factors MCM2-7, and genome-wide data showed that Separase co-localized with MCM complex and cohesin. Unexpectedly, the depletion of Separase increased the fork velocity about 1.5-fold and caused a strong acetylation of cohesin's SMC3 subunit and altered checkpoint response. Notably, Separase silencing triggered genomic instability in both HeLa and human primary fibroblast cells. Our results show a novel mechanism for fork progression mediated by Separase and thus the basis for genomic instability associated with tumorigenesis