Homogenization modelling of antibiotic diffusion and adsorption in viral liquid crystals.

Systems of rod-shaped viruses have long been important to the science of living liquid crystals, as their monodispersity and uniform charge make them convenient model systems. Recently, it was shown that, upon the addition of polymers, suspensions of rod-shaped viruses form liquid crystals that are linked with increased tolerance of bacteria against antibiotics. We use homogenization to obtain effective equations describing antibiotic diffusion through these liquid crystals. The analytical results of homogenization are compared with numerical results from an exact microscopic model, showing good agreement and thus allowing us to identify the key parameters behind the process. Our modelling shows that the adsorption plays a key role in increasing antibiotic diffusion time and therefore the presence of nematic rod-shaped viruses may increase antibiotic tolerance through physical mechanisms alone. These results demonstrate the applicability of homogenization as an analytical tool to systems of liquid crystalline viruses, with relatively straightforward extension to more complex problems such as liquid crystalline biofilms, other biological liquid crystals and biological systems with different types of local structural order.

Oral health status of Italian children with Autism Spectrum Disorder.

AIM: Autism Spectrum Disorder (ASD) is characterised by communication deficits and repetitive unusual behaviours. The behaviour guidance of these children represents a challenge for the dental team. The aim of the study was to evaluate the oral health status in a group of Italian children with ASD. MATERIALS AND METHODS: Study Design: Sixty-four Italian children with ASD and 64 controls were included. Data were collected by means of questionnaires and clinical examinations. RESULTS: Dental trauma (p=0.007), bruxism (p=0.001) and biting objects habit (p=0.021) were more frequent in the study group; fluoride exposure was lower (p=0.001) (chi-square test). The mean plaque index was 1.48 ±0.75 in the study group and 0.81±0.56 in the control group (p=0.001; Mann-Whitney U test); the mean dmft/DMFT was 3.00 ±1.2 and 2.3 ±1.8 in the study group and 1.8 ±1.1 and 1.0 ±1.1 in the control group (p<0.001; Mann-Whitney U test). Anterior open bite was more frequent in the study group (p=0.013; Chi-square test). No significant differences were found for enamel defects, molar relationship, posterior crossbite and deep bite. Significantly more children with ASD showed a negative behaviour (80% vs 35%: p =0.001; Chi-square test). CONCLUSION Children with ASD have a poorer oral health status than healthy children. The early establishment of a home dental hygiene should be encouraged.

Subgingival periodontal pathogens in Down syndrome children without periodontal breakdown. A case-control study on deciduous teeth.

AIM: Down syndrome is the most common form of aneuploidia compatible with a long survival. The affected subjects are more susceptible to severe early-onset periodontal disease and show a lower risk to develop dental caries than the non-affected population. This study investigated the prevalence of periodontal pathogens in the subgingival plaque of deciduous teeth in children with Down syndrome without signs of periodontal breakdown. METHODS: Thirty children suffering from Down syndrome and 46 matched healthy subjects were studied. A total of 228 subgingival plaque samples from deciduous teeth were separately collected and evaluated by polymerase chain reaction assays. CONCLUSION: In absence of periodontal impairment, Down syndrome children display a clear presence of periodontal pathogens already in the deciduous dentition. The hypothesis of an intrinsic predisposing condition is here supported.

Trabectedin for the therapy of ovarian cancer.

Trabectedin is a marine-derivate antitumor drug with a relevant cytotoxic activity and good safety profile. It has been investigated for the treatment of solid diseases, including ovarian cancer (OC), breast cancer, and soft-tissue sarcoma. In 2009, results from the pivotal trial OVA-301 led the European Medicines Agency (EMA) to the approval of trabectedin in combination with PEGylated liposomal doxorubicin for the treatment of platinum-sensitive recurrent OC; further studies revealed an additional benefit also in the subgroup of patients with partially platinum-sensitive disease and in those with a BRCA-mutated status. Additionally, trabectedin demonstrated to prolong the time interval to the subsequent chemotherapy line. Recently, the improved understanding of the antitumor action exerted by trabectedin paved the way to new investigational trials exploring its combination with targeted therapies.

Self-induced soft-tissue injuries following dental anesthesia in children with and without intellectual disability. A prospective study.

PURPOSE: Self-induced soft-tissue injuries (SSI) are reported as local anesthesia complications, particularly in children. The purpose of the study was to evaluate the frequency of SSI following dental anesthesia in children with and without intellectual disability. METHODS: 241 children receiving dental treatments with local anesthesia were divided into 2 groups: A, children without intellectual disability (159 individuals, 299 injections); B, children with intellectual disability (82 individuals, 165 injections). Each group was divided into subgroups according to age, injection technique and dental treatment. Two days after the dental procedure, a phone survey was conducted to determine the presence of SSI. RESULTS: The frequency of SSI in group B was 19%, with no differences in relation to gender and age. In group A the frequency of SSI was significantly lower (9%; p = 0.002; Chi-square test); the children in the ≤ 6 years-old subgroup experienced a higher frequency of SSI (p = 0.002). The lower arch was at major risk of SSI in both groups (p = 0.002). According to a multilevel approach group (p = 0.001) and injection technique (p = 0.0001) significantly influenced SSI; no influence of dental treatment is evidenced. CONCLUSIONS: SSI are common complications of local anesthesia in young children and individuals with intellectual disability.

Changes in left ventricular repolarization after short-term testosterone replacement therapy in hypogonadal males.

BACKGROUND AND AIM: Evidences suggest that androgen deficiency is associated with sudden cardiac death (SCD). Our purpose was to analyse some electrocardiographic (ECG) markers of repolarization phase in hypogonadal patients either at baseline or after testosterone replacement therapy (TRT). PATIENTS AND METHODS: Baseline and after 6 months of testosterone replacement therapy, 14 hypogonadal patients and 10 age-matched controls underwent a short-term ECG recordings at rest and immediately after a maximal exercise test. The following ECG parameters have been collected: QTe (the interval between the q wave the end of T wave), QTp (the interval between the q wave and the peak of T wave), and Te (the interval between the peak and the end of T wave). RESULTS: At baseline, in the hypogonadal patients, corrected QTe and QTp values were longer at rest than in the controls at rest (p < 0.05), whereas, during the recovery phase, only the QTp remained significantly longer (p < 0.05). After TRT, hypogonadal patients showed an improvement only in Te (p < 0.05). Conversely, any difference between hypogonadal patients and control subjects was found with respect to the markers of temporal dispersion of repolarization phases, except for a worse QTp → Te coherence (p = 0.001) obtained during the recovery phase. CONCLUSIONS: In conclusion, at rest, hypogonadal patients suffer from a stable increase in the myocardial repolarization phase without an increase in its temporal dispersion and, hence, the SCD risk seems to be low.

Needle breakage during an inferior alveolar nerve block in a child with KBG syndrome: A case report.

BACKGROUND: Needle breakage during the administration of dental analgesia is an extremely rare event. CASE REPORT: A case of needle breakage during the administration of an inferior alveolar nerve block occurred in a child with KBG syndrome. During the injection, a sudden movement of the child caused the breakage of the needle. The next day, the retrieval of the needle was performed surgically under general analgesia. FOLLOW-UP: Three months after the surgery the healing was good. Two years later the child underwent a dental extraction with the aid of nitrous oxide/oxygen analgesia/anxiolysis. CONCLUSION: Needle fracture is a possible event during the administration of dental analgesia in children.

Dental trauma in Italian children and adolescents with special health care needs. A cross-sectional retrospective study.

AIM: Dental trauma is a frequent finding in people with special health care needs. The aim of this study was to determine the prevalence of dental trauma in a sample of Italian children and adolescents with special health care needs. MATERIALS AND METHODS: 556 medical and dental records of children and adolescents visited from January 2010 to March 2015 were examined. Information about medical diagnosis, gender, site and type of dental trauma (DT) were collected. According to age and reflecting the dentition stage, the sample was divided into 3 groups: subjects aged 0-5 years (group A, primary dentition), 6-11 years (group B, mixed dentition), 12-18 years (group C, permanent dentition). RESULTS: 113 individuals experienced a DT (prevalence 20.3%), with no difference in relation to gender. Individuals with cerebral palsy and autism showed the highest frequency of DT: 39.6% and 30.4%, respectively. The highest frequency of DT occurred both in group A (21.8%) and B (21.5%), which differed significantly from group C (9%). Avulsion was the most frequent type of DT in the primary dentition (24%) and enamel-dentin fracture without pulp exposure in the permanent dentition (60%). Upper central incisors were the most affected teeth. CONCLUSION: The prevalence of DT in a sample of Italian children and adolescents with special health care needs is high, especially in young individuals with cerebral palsy and autism. Preventive strategies for those patients should be developed in order to reduce the risk of DT.

Lifting degeneracy in nematic liquid crystal viscosities with a single optical measurement.

The viscosity of complex, anisotropic fluids, such as liquid crystals or their colloidal suspensions, is characterized by a number of coefficients. Methods to measure them are, typically, sensitive only to their particular combinations, hence unable to determine them individually. Using an Ericksen-Leslie model and propagation of light through aligned layers of such materials, we show theoretically and verify experimentally how this degeneracy can be lifted by exploiting both the amplitude and frequency of the voltage applied to the cell as control parameters.

KCa3.1 inhibition switches the phenotype of glioma-infiltrating microglia/macrophages.

Among the strategies adopted by glioma to successfully invade the brain parenchyma is turning the infiltrating microglia/macrophages (M/MΦ) into allies, by shifting them toward an anti-inflammatory, pro-tumor phenotype. Both glioma and infiltrating M/MΦ cells express the Ca(2+)-activated K(+) channel (KCa3.1), and the inhibition of KCa3.1 activity on glioma cells reduces tumor infiltration in the healthy brain parenchyma. We wondered whether KCa3.1 inhibition could prevent the acquisition of a pro-tumor phenotype by M/MΦ cells, thus contributing to reduce glioma development. With this aim, we studied microglia cultured in glioma-conditioned medium or treated with IL-4, as well as M/MΦ cells acutely isolated from glioma-bearing mice and from human glioma biopsies. Under these different conditions, M/MΦ were always polarized toward an anti-inflammatory state, and preventing KCa3.1 activation by 1-[(2-Chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), we observed a switch toward a pro-inflammatory, antitumor phenotype. We identified FAK and PI3K/AKT as the molecular mechanisms involved in this phenotype switch, activated in sequence after KCa3.1. Anti-inflammatory M/MΦ have higher expression levels of KCa3.1 mRNA (kcnn4) that are reduced by KCa3.1 inhibition. In line with these findings, TRAM-34 treatment, in vivo, significantly reduced the size of tumors in glioma-bearing mice. Our data indicate that KCa3.1 channels are involved in the inhibitory effects exerted by the glioma microenvironment on infiltrating M/MΦ, suggesting a possible role as therapeutic targets in glioma.

Thermal optical non-linearity of nematic mesophase enhanced by gold nanoparticles--an experimental and numerical investigation.

In this work the mechanisms leading to the enhancement of optical nonlinearity of nematic liquid crystalline material through localized heating by doping the liquid crystals (LCs) with gold nanoparticles (GNPs) are investigated. We present some experimental and theoretical results on the effect of voltage and nanoparticle concentration on the nonlinear response of GNP-LC suspensions. The optical nonlinearity of these systems is characterized by diffraction measurements and the second order nonlinear refractive index, n2, is used to compare systems with different configurations and operating conditions. A theoretical model based on heat diffusion that takes into account the intensity and finite size of the incident beam, the nanoparticle concentration dependent absorbance of GNP doped LC systems and the presence of bounding substrates is developed and validated. We use the model to discuss the possibilities of further enhancing the optical nonlinearity.

Effects of rapid maxillary expansion and mandibular advancement on upper airways in Marfan's syndrome children: a home sleep study and cephalometric evaluation.

PURPOSE: Evaluation of the effects of rapid maxillary expansion and mandibular advancement using Propulsor Universal Light appliance on the upper airways in Marfan's syndrome children through home sleep studies, Epworth Sleepiness Scale questionnaire, and cephalometric analysis of the upper airways on lateral radiographs. METHODS: The study sample consisted of 30 children with Marfan's syndrome, and the control group consisted of 30 untreated and matched children. For Marfan subjects, data were taken at different time points compared to treatment: at T0 (before treatment), T1 (after rapid maxillary expansion), and T2 (after mandibular advancement). For control subjects, data were taken at similar intervals, at three follow-up visits: at T0 (as a starting screening tool), T1 (after approximately 2 years), and T2 (in proximity of the peak skeletal growth). RESULTS: Apnea-hypopnea and oxygen desaturations were significantly higher in the study group at T0 and T1 compared with control children. At T2, the values were not significant (p value 0.442 for both apnea-hypopnea index (AHI) and oxygen desaturation index (ODI)). Horizontal airway dimensions were significantly reduced, and vertical airway values were significantly increased in Marfan's syndrome at T0 and T1 but not at T2 (p values at T2: 0.071 for Phw1-Psp, 0.106 for Phw1-Psp', 0.101 for Phw2-Tb, 0.559 for UAL in male and 0.560 for UAL in female). CONCLUSIONS: Early rapid maxillary expansion and mandibular advancement using Propulsor Universal Light appliance significantly improved airway patency of Marfan's syndrome children and are strongly encouraged as a routine treatment for both correction of class II malocclusions and prevention of obstructive sleep apnea.

Correlation between oral health in disabled children and depressive symptoms in their mothers.

AIM: The aim of this study was to evaluate the presence and degree of depressive symptoms in mothers of disabled children and to assess the correlation between maternal major depression risk and son/daughter oral health. MATERIALS AND METHODS: A prospective study was conducted in 51 disabled children and their 51 mothers. In children dmft/DMFT values, food and/or sugar- sweetened consumption levels and daily tooth brushing frequency were evaluated. Depressive maternal symptoms were measured by EDPS questionnaire: the questionnaire scores were converted into positive predictive values (PPV) that represented the risk of falling into major depression. A regression analysis was performed on the variables (statical significance was set at p value ≤ 0.05). RESULTS: Children (8.68 ± 3.98 years old) average dmft/DMFT was 2.7. Fifty three percent of the mothers (38.37 ± 6.04 years) were at risk for depression (PPV > 60%), while depressive symptoms were already present in 25% of the subjects (PPV=100%). DISCUSSION AND CONCLUSION: Mothers of disabled children are more likely to fall into major depression compared to mothers of healthy children. For each mother-child couple the correlation between different variables was evaluated: there was a statistically significant correlation between children's dmft/DMFT values and mothers' depression risk. The risk of maternal depression was statistically correlated to prevalence of caries and sugar consumption in children.

Gold nanoparticle liquid crystal composites as a tunable nonlinear medium.

We investigate the nonlinearity of a liquid crystal cell doped with gold nanoparticles by considering their selective absorption. Such nonlinearities are promising for optical processing applications and optical limiters. Systems displaying thermal nonlinearities are particularly attractive as the maximum nonlinearity may occur in the absence of an applied field and additionally this nonlinearity can be controlled by the reorientation of the liquid crystal. We show that there exists a theoretical optimum concentration of absorbers, which maximizes the nonlinearity. Further we show that the nonlinearity of the system can be tuned by the reorientation of the liquid crystal host, with the nonlinearity decreasing from 9 × 10(-5) cm(2)W(-1) to zero by the application of a magnetic field of the order of 0.01 Tesla. This allows a fine control of the diffraction efficiency and, in principle, many other nonlinear effects.

Voltage transfer function as an optical method to characterize electrical properties of liquid crystal devices.

The voltage transfer function is a rapid and visually effective method to determine the electrical response of liquid crystal (LC) systems using optical measurements. This method relies on crosspolarized intensity measurements as a function of the frequency and amplitude of the voltage applied to the device. Coupled with a mathematical model of the device it can be used to determine the device time constants and electrical properties. We validate the method using photorefractive LC cells and determine the main time constants and the voltage dropped across the layers using a simple nonlinear filter model.

Oral health and dental late adverse effects in children in remission from malignant disease. A pilot case-control study in Italian children.

AIM: To investigate with a reliable method the oral features in Italian patients in remission from cancer, highlighting the relationship with age at cancer therapy and to compare the data with healthy controls. MATERIALS AND METHODS: Twenty five childhood cancer survivors treated under the age of 10 years with chemotherapy w/wo Haemopoietic Stem Cell Transplantation and/or head-neck Radiotherapy, in remission from cancer for at least 3 years, were examined for dental caries and enamel defects. To assess dental age and dental abnormalities a panoramic radiograph was taken. Patients were grouped according to age at cancer therapy (<3 years: subgroup Y; 3.1-5 years: subgroup M; >5 years: subgroup O). A control group of 26 healthy children was included. RESULTS: There was not a statistically significant difference in caries prevalence between the two groups. A statistically significant difference between the two groups was found for enamel defects, dental abnormalities and dental age. The chi-squared test revealed a relationship between age at therapy and specific dental abnormalities. CONCLUSION: This study shows that cancer therapy may increase the risk of development of enamel defects and dental abnormalities, especially in children treated under the age of 3 years.

Multiscale models of colloidal dispersion of particles in nematic liquid crystals.

We use homogenization theory to develop a multiscale model of colloidal dispersion of particles in nematic liquid crystals under weak-anchoring conditions. We validate the model by comparing it with simulations by using the Landau-de Gennes free energy and show that the agreement is excellent. We then use the multiscale model to study the effect that particle anisotropy has on the liquid crystal: spherically symmetric particles always reduce the effective elastic constant. Asymmetric particles introduce an effective alignment field that can increase the Fredericks threshold and decrease the switch-off time.

Aorfix™ device for abdominal aortic aneurysm with challenging anatomy.

Anatomical characteristics of abdominal aortic aneurysms (AAA) are the most critical factors for successful endovascular aortic repair (EVAR). Of these, severe proximal aortic neck angulation and iliac axis tortuosity increase the complexity of EVAR. Neck angulation seems to have a pivotal potential for fixation failure, a situation that may lead to complications, including endoleak and late rupture. Bench-test studies identified that the relative stiffness of a stent-graft was responsible for its inability to conform to neck angulation, therefore creating leaks through gaps between the stent graft and the neck. Aorfix™ stent graft (Lombard Medical, Didcot, UK) is a flexible stent-graft designed and manufactured with the purpose of overcoming the issue of stent-graft stiffness. Many studies have shown good results in term of procedural success and mid-term type-I endoleak. PYTHAGORAS trial evaluated mainly patients with highly angulated infrarenal neck and showed that high performance of Aorfix™ stent graft did not present any significant difference between neck >60° and <60°. In the series of 27 patients treated at our Institution we had a primary technical success of 96.3% and an assisted primary technical success of 100%. In this review we will analyze the available data in literature regarding Aorfix™ stent graft and will discuss the outcome of the patients treated with Aorfix™ stent graft at our centre.

KCa3.1 channels are involved in the infiltrative behavior of glioblastoma in vivo.

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