Buccal Alveolar Bone changes and upper first molar displacement after maxillary expansion with RME, Ni-Ti leaf springs expander and Tooth- Bone-borne Expander. A CBCT based analysis.

AIM: To evaluate the buccal alveolar bone changes and the upper first molar displacement in subjects treated with conventional rapid maxillary expansion (RME), Ni-Ti leaf springs expander (Leaf Expander) and Tooth-Bone-borne Expander (Hybrid Expander) using CBCT scans. METHODS: The sample consisted of 52 children treated with RME (n=18), Leaf Expander (n= 17) and Hybrid Expander (n= 17). CBCTs were taken before and after maxillary expansion and the Horos software was used for the analysis. Descriptive statistics and paired t-test were used to assess changes between the pre-treatment and post-treatment measurements. ANOVA test and Tukey's post hoc test with Bonferroni correction was used for between groups comparison. CONCLUSION: The Hybrid Expander during preadolescence showed few advantages over the use of tooth-anchored expanders. An expansion approach with mini-screws is not preferable during early mixed dentition to a conventional approach. The differences in dental tipping values were clinically insignificant and the reduction in cortical bone thickness remained less than 1 mm. When possible, the use of second primary molars as anchorage should be preferred.

In situ electroporation of mammalian cells through SiO2 thin film capacitive microelectrodes.

Electroporation is a widely used non-viral technique for the delivery of molecules, including nucleic acids, into cells. Recently, electronic microsystems that miniaturize the electroporation machinery have been developed as a new tool for genetic manipulation of cells in vitro, by integrating metal microelectrodes in the culture substrate and enabling electroporation in-situ. We report that non-faradic SiO2 thin film-insulated microelectrodes can be used for reliable and spatially selective in-situ electroporation of mammalian cells. CHO-K1 and SH-SY5Y cell lines and primary neuronal cultures were electroporated by application of short and low amplitude voltage transients leading to cell electroporation by capacitive currents. We demonstrate reliable delivery of DNA plasmids and exogenous gene expression, accompanied by high spatial selectivity and cell viability, even with differentiated neurons. Finally, we show that SiO2 thin film-insulated microelectrodes support a double and serial transfection of the targeted cells.

Tuberculosis screening in outpatient healthcare workers: lessons from a high-income, low TB burden country.

SETTING: Early diagnosis of latent tuberculous infection (LTBI) should be pursued in healthcare workers (HCWs). While HCWs in hospitals are screened for LTBI, HCWs in outpatient settings are usually not. In 2017, in Italy, a tuberculosis (TB) infected paediatrician working in an outpatient vaccination service infected 15 adults and nine children. The investigation involved 2490 children and 151 adults. Among children, nine were tuberculin skin test-positive, and four developed active TB. Among 123 adult contacts with longer exposure, seven were interferon-gamma release assay (IGRA) positive and none had active TB. Among 28 close contacts, eight had a positive IGRA, and three had pulmonary TB. The total outbreak cost €1 017 903.OBJECTIVE: To compare the outbreak cost with those of potential screening programme strategies.RESULTS: Regular screening of paediatric outpatient HCWs would have cost between €2592 and €11 373. Extending the screening to all outpatient HCWs (caring for adults and children) would have cost between €66 384 and €155 043. Investigating only close contacts would have cost €42 857.CONCLUSION: Each of these screening strategies would have been cost-effective compared with the outbreak investigation occurring in real life with a cut-off of 474 for the maximum number of tested outpatient HCWs needed for the screening strategy to be cost-saving.

Neuropsychiatric adverse events of antiepileptic drugs in brain tumour-related epilepsy: an Italian multicentre prospective observational study.

BACKGROUND AND PURPOSE: We assessed the prevalence and magnitude of neuropsychiatric adverse events (NPAEs) associated with antiepileptic drugs (AEDs) among patients with brain tumour-related epilepsy (BTRE). METHODS: This observational, prospective, multicentre study enrolled 259 patients with BTRE after neurosurgery. All patients received AED monotherapy. Efficacy was assessed through clinical diaries, whereas NPAEs were collected using the Neuropsychiatric Inventory Test-12 questionnaire at baseline and after 5 months. RESULTS: Tumour localization in the frontal lobe was associated with a higher prevalence of NPAEs (odds ratio, 7.73; P < 0.001). Independent of tumour localization, levetiracetam (LVT) treatment was associated with higher prevalence and magnitude of NPAEs (odds ratio, 7.94; P < 0.01) compared with other AEDs. Patients with oligodendroglioma reported more NPAEs than patients with other tumour types. NPAEs were not influenced by chemotherapy, radiotherapy or steroid treatment. Evaluating non-neurobehavioural adverse events of AEDs, no significant differences were found among AEDs, although patients treated with old AEDs had a higher prevalence of adverse events than those treated with new AEDs. CONCLUSIONS: Both tumour localization in the frontal lobe and LVT treatment are associated with a higher risk of NPAEs in patients with BTRE. LVT is regarded as a first-line option in patients with BTRE because of easy titration and few significant drug-to-drug interactions. Thus, as NPAEs lead to poor compliance and a high dropout rate, clinicians need to accurately monitor NPAEs after AED prescription, especially in patients with frontal lobe tumours receiving LVT.

Evaluation of risk of symptomatic cytomegalovirus reactivation in myeloma patients treated with tandem autologous stem cell transplantation and novel agents: a single-institution study.

The introduction of proteasome inhibitors and/or immunomodulators in the treatment of myeloma has led to an increase in viral infections, particularly in the Herpesviridae family. Previous studies about the risk of cytomegalovirus (CMV) reactivation after autologous stem cell transplantation (ASCT) have examined the clinical outcome after the first ASCT; however, only 1 study to date has investigated the risk of CMV reactivation after a second transplantation. To address this issue, we performed a retrospective chart review on 78 consecutive myeloma patients (median age 56 years) who underwent a tandem non-CD34(+) selected ASCT after induction treatment with either conventional chemotherapy (n = 42) or with novel agents (n = 36), respectively. All subjects had been mobilized and conditioned with cyclophosphamide plus granulocyte colony-stimulating factor and melphalan alone, respectively. CMV DNA load in the blood has been determined by polymerase chain reaction in the case of a clinical suspicion of CMV reactivation; therefore, routine monitoring was not performed. Considering the outcome of both the first and the second transplantations, we observed a total of 13 episodes of symptomatic CMV reactivation (13/156, 8%), in 12 subjects (12/78, 15%), all successfully treated. Eight subjects experienced a CMV reactivation after the first ASCT (8/78, 10%); however, only 1 of them (1/8, 12%) experienced a CMV reactivation after the second transplantation. Conversely, 4 CMV reactivations (6%) were observed after the second transplantation in the group of 70 patients who did not experience a CMV reactivation after the first ASCT. No statistically significant difference was observed between first and second ASCT (8/78, 10% vs. 5/78, 6%; P = 0.767). Univariate analysis showed that a pre-transplant treatment with novel agents was the only baseline factor significantly associated with the occurrence of post-ASCT CMV symptomatic reactivation after the first transplant (odds ratio [OR]: 9.897; 95% confidence interval [CI]: 1.154-84.840; P = 0.021) but not after the second transplant (OR: 5.125; 95% CI: 0.546-48.119; P = 0.115). No end-organ disease or primary infection was documented. Our data suggest that second transplantation does not increase the risk of CMV reactivation in our patient population, when compared with the first one, and confirm the role of a pre-transplant treatment with novel agents as a risk factor for CMV symptomatic reactivation.

Screening for impaired glucose tolerance in obese children and adolescents: a validation and implementation study.

UNLABELLED: What is already known about this subject Fasting triglycerides above 1.17 mmol/L have been shown to be useful to select obese children and adolescents who may present impaired glucose tolerance in a Canadian cohort. Fasting plasma glucose is associated with the risk to present impaired glucose tolerance in several cohorts of obese children and adolescents. What this study adds When applied to Italian cohorts of obese children and adolescents, the triglycerides cut-off of 1.17 mmol/L has similar validity as in the Canadian cohort to select patients who may present impaired glucose tolerance. Fasting plasma glucose and fasting triglycerides can be combined to obtain an accurate criterion to select obese children and adolescents who may present impaired glucose tolerance. OBJECTIVES: We aimed to validate fasting triglycerides > 1.17 mmol L(-1) , a criterion recently proposed for selecting obese children at risk of impaired glucose tolerance (IGT), and to assess whether the accuracy of triglycerides (TG) can be improved by the use of other variables. METHODS: We studied an Italian cohort of 817 obese children and adolescents (8-18.4 years) who underwent clinical examination, fasting blood analysis and the oral glucose tolerance test (OGTT). The discriminative properties of TG > 1.17 mmol L(-1) were assessed and compared with those observed in a Canadian cohort from which this criterion was derived: 71.4 [57.8-85.1]% sensitivity and 64.1 [57.7-70.4]% specificity. The possible contribution of other variables was evaluated by assessing the net reclassification improvement (NRI), i.e., the net increase in the percentage of subjects correctly classified. RESULTS: Thirty-nine children (4.7%) had IGT. The 1.17 mmol L(-1) TG threshold showed 66.6 [51.8-81.4]% sensitivity and 68.2 [64.9-71.5]% specificity, thus successfully validated. Fasting plasma glucose (FPG) was independently associated with IGT (odds ratio = 3.86 [2.09-7.14], P < 0.001), besides TG. The bivariate criterion of TG ≥ 1.13 mmol L(-1) plus FPG ≥ 4.44 mmol L(-1) had a 69.2 [54.7-83.7]% sensitivity and a 78.2 [76.8-79.6]% specificity, thus displaying a 12.6% NRI (P < 0.001) compared with TG>1.17 mmol L(-1) . CONCLUSIONS: TG > 1.17 mmol L(-1) is a useful criterion to detect roughly 66% of obese children with IGT through OGTT performed in about 33% of all obese children. However, the 'TG≥1.13 mmol L(-1) plus FPG≥4.44 mmol L(-1) ' criterion improved discrimination accuracy, leading to the possibility of detecting even more than 66% of obese children with IGT though limiting OGTT to just 25% of all obese children.

Metabolic and hormonal consequences of two different meals after a moderate intensity exercise bout in obese prepubertal children.

BACKGROUND/OBJECTIVES: To investigate the relationship between postprandial nutrient balance, satiety and hormone changes induced by two different meals taken after a moderate intensity exercise bout. SUBJECTS/METHODS: Ten prepubertal obese children participated in the study. The experiment was designed as a cross-over study for repeated measures. Each test period lasted five consecutive hours during which the children were under medical supervision. The effects of two isocaloric meals were compared after a moderate intensity exercise (4 multiples of resting metabolic rate, 30 min, cycling): a low-fat/high-carbohydrate meal (meal A) and a high-fat/low-carbohydrate meal (meal B). Pre and postprandial (3 h) substrate oxidation, biochemical parameters, gastrointestinal hormone concentrations and appetite were measured. RESULTS: The main results were: (i) higher fat balance (5.1±5.0 vs -5.0±6.6 g, P=0.001) and lower carbohydrate balance after meal B than A (-9.7±13.3 vs 11.3±18.3 g, P<0.01); (ii) higher energy balance after meal B than after meal A (5.9±21.5 vs -13.9±20.2 kcal, P<0.05); (iii) higher plasma triglyceride concentrations (area under the curve) after meal B than after meal A (2962.5±2095.8 mg*180 min/dl vs -169.5±1633.7 mg*180 min/dl, P<0.01); (iv) higher serum glucagon-like peptide-1 concentrations after meal B than after meal A (1101.5±873.0 pmol*180 min/l vs 478.8±638.3 pmol*180 min/l, P<0.05). CONCLUSIONS: After a bout of moderate intensity exercise, a meal with a high-fat/low-carbohydrate ratio had a less favorable metabolic impact than an isoenergetic, isoproteic low-fat/high-carbohydrate meal.

Diet macronutrient composition reported before treatment predicts BMI change in obese children: the role of lipids.

In this study, we tested the hypothesis that diet composition reported by children before the beginning of an obesity treatment program could be a predicting factor of the clinical outcome. A sample of 138 obese 6-16-year-old children and adolescents were recruited. Anthropometry and dietary habits were recorded. Each patient participated in a multidimensional treatment program in an outpatient obesity public service clinic. Therapy was based on a 6-month educational program on nutrition, lifestyle and physical activity. Children with a lipid intake above 34.7% of total energy had a 2.5 times higher chance of reducing at least 1.5 units of BMI with treatment than children with lower lipid intake. These results suggest that the assessment of habitual diet, in particular diet composition before starting treatment, may help to identify obese children who are more sensitive to intervention and those who need more specific nutritional assistance.

Trigeminal neuralgia as unusual isolated symptom of fungal paranasal sinusitis in patients with haematological malignancies.

A sinonasal infection is a frequent complication in patients with haematological malignancies, and may represent a challenge in terms of differential diagnosis between a bacterial or fungal infective process and tumour localization. A timely and correct diagnosis in these patients is critical and, therefore, may require consultation of specialists outside of haematology; an incorrect diagnosis which underestimates the seriousness of the infection can be fatal. Symptomatic trigeminal neuralgia resulting from direct compression or perineural invasion from malignancy is not uncommon in the literature. However, trigeminal neuralgia as an isolated symptom at the onset of a bacterial or invasive fungal sinusitis is rare and risks going unnoticed. The authors herein describe three cases of patients affected by acute myeloid leukaemia or lymphoma in which an invasive fungal sinusitis appeared at the onset as an isolated trigeminal neuralgia, with pain located along the distribution area of the second branch of the trigeminal nerve. Only after referring these patients to a neurologist for a host of neurological exams it was possible to confirm a diagnosis of secondary maxillary sinus fungal involvement.

Oxcarbazepine monotherapy in patients with brain tumor-related epilepsy: open-label pilot study for assessing the efficacy, tolerability and impact on quality of life.

We conducted a prospective, observational study to verify the efficacy, tolerability and impact on quality of life, mood and global neurocognitive performances of oxcarbazepine monotherapy in patients with brain tumor-related epilepsy (BTRE). Patients were followed for 12 months. We recruited 25 patients (11 females 14 males; mean age 49.7) affected with BTRE (17 de novo patients and 7 in monotherapy with other antiepileptics) and introduced oxcarbazepine monotherapy because of uncontrolled seizures and/or side effects. At first visit, patients underwent neurological examination, Qolie 31P V2, EORTC QLQC30, Zung self-depression rating scale (ZSDRS) and adverse events profile. A seizure diary was given to each patient. Follow-up duration was 1-12 months (mean 7.1 months, 5 patients died and 10 dropped out). Totals of 16 patients underwent both chemotherapy and radiotherapy, 4 chemotherapy only, 1 radiotherapy only, and 4 did not undergo any systemic therapy. Mean dosage of oxcarbazepine was 1,230 mg/day (min 600, max 2,100 mg/day). McNemar's test showed a significant difference in seizure freedom rate (P = 0.002) between baseline and final follow-up in the intent-to-treat population. Six patients (24%) had serious side effects and one patient (4%) mild. Logistic regression revealed that, in our study, chemotherapy and radiotherapy did not affect the efficacy of OXC in seizure outcome (P = 0.658). The test evaluation at final follow-up showed a significant improvement in ZSDRS (P = 0.011) and no change over time. Oxcarbazepine seems to be efficacious in controlling seizures and in improving mood in patients with BTRE, but special caution should be taken when it is administered during radiotherapy.

Lacosamide as add-on in brain tumor-related epilepsy: preliminary report on efficacy and tolerability.

Lacosamide (LCM) is an antiepileptic drug (AED) that has demonstrated a good efficacy in controlling seizures as an add-on in adult epilepsy. To date, there have been no studies on LCM in patients with brain tumor-related epilepsy (BTRE). To evaluate efficacy and tolerability of LCM as an add-on in BTRE, we followed 14 patients suffering from BTRE who had already been treated with other AEDs and who had not experienced adequate seizure control. Eleven patients underwent chemotherapy while being treated with LCM. Mean duration of follow up was 5.4 months (min < 1 max 10 months). Mean seizure number in the last month prior to the introduction of LCM had been 15.4. At last follow-up, the mean seizure number was reduced to 1.9/month. Lacosamide mean dosage was of 332.1 mg/day (min 100 max 400 mg/day). Responder rate was 78.6%. One patient discontinued LCM because of side-effects. There were no other reported side-effects. Preliminary data on the use of LCM in add-on in patients with BTRE indicate that this drug may represent a valid alternative as an add-on in this particular patient population. However, larger samples are necessary in order to draw definitive conclusions.

Mechanical and electrophysiological properties of the sarcolemma of muscle fibers in two murine models of muscle dystrophy: col6a1-/- and mdx.

This study aimed to analyse the sarcolemma of Col6a1-/- fibers in comparison with wild type and mdx fibers, taken as positive control in view of the known structural and functional alterations of their membranes. Structural and mechanical properties were studied in single muscle fibers prepared from FDB muscle using atomic force microscopy (AFM) and conventional electrophysiological techniques to measure ionic conductance and capacitance. While the sarcolemma topography was preserved in both types of dystrophic fibers, membrane elasticity was significantly reduced in Col6a1-/- and increased in mdx fibers. In the membrane of Col6a1-/- fibers ionic conductance was increased likely due to an increased leakage, whereas capacitance was reduced, and the action potential (ap) depolarization rate was reduced. The picture emerging from experiments on fibers in culture was consistent with that obtained on intact freshly dissected muscle. Mdx fibers in culture showed a reduction of both membrane conductance and capacitance. In contrast, in mdx intact FDB muscle resting conductance was increased while resting potential and ap depolarization rate were reduced, likely indicating the presence of a consistent population of severely altered fibers which disappear during the culture preparation.

Antiepileptics in brain metastases: safety, efficacy and impact on life expectancy.

The aim of the study was to evaluate efficacy, safety and impact on life expectancy of levetiracetam (LEV), oxcarbazepine (OXC) and topiramate (TPM) monotherapy in patients with seizures related to brain metastases. We conducted a prospective observational study on 70 patients with brain metastases. Thirteen patients were excluded because they were in prophylactic therapy with antiepileptics, nine patients did not return to our Center. A total of 48 patients with epilepsy related to brain metastases were enrolled. Patients were treated with LEV, OXC and TPM in monotherapy and followed until their death. Eighteen patients dropped out. Therefore, we followed 30 patients. Mean duration of follow-up was 6.1 months. Upon visiting the patients prior to their death (i.e. last visit preceding the death of the patients), we observed a significant reduction (P < 0.001) in the mean monthly seizure frequency; with 19 patients (63.3%) obtaining complete seizure control in the whole population. A significant improvement of seizure frequency was also observed considering each antiepileptic treatment group separately. Median survival time was similar among the three groups of patients and was similar to Class I of prognostic factors of Radiation Therapy Oncology Group. Logistic regression showed that systemic treatments did not influence the antiepileptics' efficacy on seizure control (P = 0.614). In conclusion, regarding the use of newer antiepileptics in patients with seizures related to brain metastases, our data indicate that LEV, OXC and TPM significantly reduce seizure frequency (independently of systemic treatment), produce few side effects and appear not to affect life expectancy.

Efficacy and tolerability of zonisamide as add-on in brain tumor-related epilepsy: preliminary report.

BACKGROUND: Zonisamide (ZNS) is an antiepileptic drug (AED) with broad spectrum action that demonstrated a good efficacy in controlling seizures as add-on in adult and pediatric epilepsy. To date there have been no studies on ZNS in patients with brain tumor-related epilepsy (BTRE). AIM OF THE STUDY: To evaluate efficacy and tolerability of ZNS as add-on in BTRE. METHODS: We followed six patients suffering from BTRE who had already been treated with other AEDs and who had had not experienced adequate seizure control. Three patients underwent chemotherapy while being treated with ZNS. Mean duration of follow-up was 8 months. RESULTS: Mean seizure number in the last month prior to the introduction of ZNS had been 27.7/month. ZNS mean dosage was of 283.3 mg/day. At last follow-up, the mean seizure number was reduced to 8.8/month. Responder rate was 83.3%.Two patients discontinued the drug because of side effects. There were no other reported side effects. CONCLUSIONS: Preliminary data on the use of ZNS in add-on in patients with BTRE indicate that this drug may represent a valid alternative as add-on in this particular patient population. However, larger samples are necessary to draw definitive conclusions.

Space and time-resolved gene expression experiments on cultured mammalian cells by a single-cell electroporation microarray.

Single-cell experiments represent the next frontier for biochemical and gene expression research. Although bulk-scale methods averaging populations of cells have been traditionally used to investigate cellular behavior, they mask individual cell features and can lead to misleading or insufficient biological results. We report on a single-cell electroporation microarray enabling the transfection of pre-selected individual cells at different sites within the same culture (space-resolved), at arbitrarily chosen time points and even sequentially to the same cells (time-resolved). Delivery of impermeant molecules by single-cell electroporation was first proven to be finely tunable by acting on the electroporation protocol and then optimized for transfection of nucleic acids into Chinese Hamster Ovary (CHO-K1) cells. We focused on DNA oligonucleotides (ODNs), short interfering RNAs (siRNAs), and DNA plasmid vectors, thus providing a versatile and easy-to-use platform for time-resolved gene expression experiments in single mammalian cells.