Family Pediatrician and Public Health collaboration, an alliance to increase vaccination coverage: an experience with MenB vaccination in Italy.

Background: Invasive Meningococcal Disease is a severe disease mainly affecting infants and young children. Most infections are caused by serogroups A, B, C, W, X, and Y. In the last 10 years, serogroup B has been the main cause of Invasive Meningococcal Disease in Europe. Recent data resulting from an observational study conducted in Italy show a significant reduction in the number of Invasive Meningococcal Disease cases due to Neisseria meningitidis B after the introduction of vaccine 4CMenB. Thus, the Naples Team of Federation of Italian Primary Care Pediatricians and the Public Health Department started an active collaboration focused on vaccination process management (named "Progetto Via") with the aim of increasing Meningococcal B vaccination coverage. Study design: Source of data is the regional platform "GE.VA.". Every Primary care Pediatrician uses daily to record vaccination activity. This platform is integrated with data entered by operators of the District/Vaccination Center. Methods: Time: January 2019 - December 2019. The Federation of Italian Primary Care Pediatricians/Naples organized a meeting to identify six coordinators. The pediatricians could choose to counsel in their own offices and send children to the vaccination center or to counsel and vaccinate directly in their own clinics. Results: A total of 78 pediatricians took part in the project: 46 did only counseling and 32 did both counseling and vaccination in their medical clinic. Data obtained show an overall average vaccination coverage growth of about 13% in the first 4 months of the survey, and a further growth of about 11% in the following seven months, with a total growth in the entire period of 24%. The pediatricians' counseling is essential to recover non-compliant subjects, considering both the relationship of trust with the families and the visits already scheduled as an ideal moment for vaccinations' status check. Conclusions: The project highlights how an effective collaboration between family pediatricians and the Local Health Authority becomes valuable in getting closer to reach the Ministerial goal of 95%. Vaccination coverage increased significantly when family pediatricians supported the activity of vaccine centers in distress in many regional situations. The trust relationship, the hourly availability and the capillary network of family pediatricians' clinics were key elements for the success of this project and were also recognized by parents.

Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort.

INTRODUCTION: Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments. METHODS: A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation. RESULTS: Participants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability. DISCUSSION: f-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.

Active lifestyles moderate clinical outcomes in autosomal dominant frontotemporal degeneration.

INTRODUCTION: Leisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD). METHODS: A total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non-carriers reported current physical and cognitive activities at baseline, and completed longitudinal neurobehavioral assessments and brain magnetic resonance imaging (MRI) scans. RESULTS: Greater physical and cognitive activities were each associated with an estimated >55% slower clinical decline per year among dominant gene carriers. There was also an interaction between leisure activities and frontotemporal atrophy on cognition in mutation carriers. High-activity carriers with frontotemporal atrophy (-1 standard deviation/year) demonstrated >two-fold better cognitive performances per year compared to their less active peers with comparable atrophy rates. DISCUSSION: Active lifestyles were associated with less functional decline and moderated brain-to-behavior relationships longitudinally. More active carriers "outperformed" brain volume, commensurate with a cognitive reserve hypothesis. Lifestyle may confer clinical resilience, even in autosomal dominant FTLD.

Near-infrared modulation by means of GeTe/SOI-based metamaterial.

Today, nanophotonics still lacks components for modulation that can be easily implementable in existing silicon-on-insulator (SOI) technology. Chalcogenide phase change materials (PCMs) are promising candidates for tuning in the near infrared: at the nanoscale, thin layers can provide enough contrast to control the optical response of a nanostructure. Moreover, all-dielectric metamaterials allow for resonant behavior without having ohmic losses in the telecom range. Here, a novel hybridization of a SOI-based metamaterial with PCM GeTe is experimentally investigated. A metamaterial based on Si nanorods, covered by a thin layer of GeTe, is designed and fabricated. Switching GeTe from amorphous to crystalline leads to a rather high resonance-governed reflection contrast at 1.55 µm. Additional confocal Raman imaging is done to differentiate the crystallized zones of the metamaterials' unit cell. The findings are in good agreement with numerical analysis and show good perspectives of all-dielectric tunable near-infrared nanophotonics.

Management of psychogenic non-epileptic seizures: a multidisciplinary approach.

The International League against Epilepsy (ILAE) proposed a diagnostic scheme for psychogenic non-epileptic seizure (PNES). The debate on ethical aspects of the diagnostic procedures is ongoing, the treatment is not standardized and management might differ according to age group. The objective was to reach an expert and stakeholder consensus on PNES management. A board comprising adult and child neurologists, neuropsychologists, psychiatrists, pharmacologists, experts in forensic medicine and bioethics as well as patients' representatives was formed. The board chose five main topics regarding PNES: diagnosis; ethical issues; psychiatric comorbidities; psychological treatment; and pharmacological treatment. After a systematic review of the literature, the board met in a consensus conference in Catanzaro (Italy). Further consultations using a model of Delphi panel were held. The global level of evidence for all topics was low. Even though most questions were formulated separately for children/adolescents and adults, no major age-related differences emerged. The board established that the approach to PNES diagnosis should comply with ILAE recommendations. Seizure induction was considered ethical, preferring the least invasive techniques. The board recommended looking carefully for mood disturbances, personality disorders and psychic trauma in persons with PNES and considering cognitive-behavioural therapy as a first-line psychological approach and pharmacological treatment to manage comorbid conditions, namely anxiety and depression. Psychogenic non-epileptic seizure management should be multidisciplinary. High-quality long-term studies are needed to standardize PNES management.

Reducing Phonon-Induced Decoherence in Solid-State Single-Photon Sources with Cavity Quantum Electrodynamics.

Solid-state emitters are excellent candidates for developing integrated sources of single photons. Yet, phonons degrade the photon indistinguishability both through pure dephasing of the zero-phonon line and through phonon-assisted emission. Here, we study theoretically and experimentally the indistinguishability of photons emitted by a semiconductor quantum dot in a microcavity as a function of temperature. We show that a large coupling to a high quality factor cavity can simultaneously reduce the effect of both phonon-induced sources of decoherence. It first limits the effect of pure dephasing on the zero-phonon line with indistinguishabilities above 97% up to 18 K. Moreover, it efficiently redirects the phonon sidebands into the zero-phonon line and brings the indistinguishability of the full emission spectrum from 87% (24%) without cavity effect to more than 99% (76%) at 0K (20K). We provide guidelines for optimal cavity designs that further minimize the phonon-induced decoherence.

Increased CYFIP1 dosage alters cellular and dendritic morphology and dysregulates mTOR.

Rare maternally inherited duplications at 15q11-13 are observed in ~1% of individuals with an autism spectrum disorder (ASD), making it among the most common causes of ASD. 15q11-13 comprises a complex region, and as this copy number variation encompasses many genes, it is important to explore individual genotype-phenotype relationships. Cytoplasmic FMR1-interacting protein 1 (CYFIP1) is of particular interest because of its interaction with Fragile X mental retardation protein (FMRP), its upregulation in transformed lymphoblastoid cell lines from patients with duplications at 15q11-13 and ASD and the presence of smaller overlapping deletions of CYFIP1 in patients with schizophrenia and intellectual disability. Here, we confirm that CYFIP1 is upregulated in transformed lymphoblastoid cell lines and demonstrate its upregulation in the post-mortem brain from 15q11-13 duplication patients for the first time. To investigate how increased CYFIP1 dosage might predispose to neurodevelopmental disease, we studied the consequence of its overexpression in multiple systems. We show that overexpression of CYFIP1 results in morphological abnormalities including cellular hypertrophy in SY5Y cells and differentiated mouse neuronal progenitors. We validate these results in vivo by generating a BAC transgenic mouse, which overexpresses Cyfip1 under the endogenous promotor, observing an increase in the proportion of mature dendritic spines and dendritic spine density. Gene expression profiling on embryonic day 15 suggested the dysregulation of mammalian target of rapamycin (mTOR) signaling, which was confirmed at the protein level. Importantly, similar evidence of mTOR-related dysregulation was seen in brains from 15q11-13 duplication patients with ASD. Finally, treatment of differentiated mouse neuronal progenitors with an mTOR inhibitor (rapamycin) rescued the morphological abnormalities resulting from CYFIP1 overexpression. Together, these data show that CYFIP1 overexpression results in specific cellular phenotypes and implicate modulation by mTOR signaling, further emphasizing its role as a potential convergent pathway in some forms of ASD.

Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease.

We have sequenced the complete genomes of 72 individuals affected with early-onset familial Alzheimer's disease caused by an autosomal dominant, highly penetrant mutation in the presenilin-1 (PSEN1) gene, and performed genome-wide association testing to identify variants that modify age at onset (AAO) of Alzheimer's disease. Our analysis identified a haplotype of single-nucleotide polymorphisms (SNPs) on chromosome 17 within a chemokine gene cluster associated with delayed onset of mild-cognitive impairment and dementia. Individuals carrying this haplotype had a mean AAO of mild-cognitive impairment at 51.0 ± 5.2 years compared with 41.1 ± 7.4 years for those without these SNPs. This haplotype thus appears to modify Alzheimer's AAO, conferring a large (~10 years) protective effect. The associated locus harbors several chemokines including eotaxin-1 encoded by CCL11, and the haplotype includes a missense polymorphism in this gene. Validating this association, we found plasma eotaxin-1 levels were correlated with disease AAO in an independent cohort from the University of California San Francisco Memory and Aging Center. In this second cohort, the associated haplotype disrupted the typical age-associated increase of eotaxin-1 levels, suggesting a complex regulatory role for this haplotype in the general population. Altogether, these results suggest eotaxin-1 as a novel modifier of Alzheimer's disease AAO and open potential avenues for therapy.

The use of illicit drugs as self-medication in the treatment of cluster headache: Results from an Italian online survey.

BACKGROUND: Cluster headache (CH) patients often receive unsatisfactory treatment and may explore illicit substances as alternatives. We aimed to explore this use of illicit drugs for CH treatment. METHODS: We invited CH patients from an Internet-based self-help group to complete a questionnaire regarding their therapeutic use of illicit substances. RESULTS: Of the 54 respondents, 29 were classified as chronic and 39 were drug-resistant cases. Fifty patients had previously tried subcutaneous sumatriptan, 40 had tried O2, and 48 had tried at least one prophylactic treatment. All 54 patients specified that they were dissatisfied with conventional treatments. Thirty-four patients had used cannabinoids, 13 cocaine, 8 heroin, 18 psilocybin, 12 lysergic acid amide (LSA), and 4 lysergic acid diethylamide (LSD). DISCUSSION: Some patients with intractable CH decided to try illicit drugs concomitantly with cessation of medical care. Most of these patients found suggestions for illicit drug use on the Internet. Many patients seemed to underestimate the judicial consequences of, and had an overestimated confidence in the safety of, such illicit treatments. Physicians are often not informed by patients of their choice to use illicit drugs. This leads to questions regarding the true nature of the physician-patient relationship among dissatisfied CH patients.

Clinical dissection of childhood occipital epilepsy of Gastaut and prognostic implication.

BACKGROUND AND PURPOSE: Our aim was to describe the clinical and electrical features and the long-term evolution of childhood occipital epilepsy of Gastaut (COE-G) in a cohort of patients and to compare long-term prognosis between patients with and without other epileptic syndromes. METHODS: This was a retrospective analysis of the long-term outcome of epilepsy in 129 patients with COE-G who were referred to 23 Italian epilepsy centres and one in Austria between 1991 and 2004. Patients were evaluated clinically and with electroencephalograms for 10.1-23.0 years. The following clinical characteristics were evaluated: gender, patient age at seizure onset, history of febrile seizures and migraine, family history of epilepsy, duration and seizure manifestations, circadian distribution and frequency of seizures, history of medications including the number of drugs, therapeutic response and final outcome. RESULTS: Visual hallucinations were the first symptom in 62% and the only manifestation in 38.8% of patients. Patients were subdivided into two groups: group A with isolated COE-G; group B with other epileptic syndromes associated with COE-G. The most significant (P < 0.05) difference concerned antiepileptic therapy: in group A, 45 children responded to monotherapy; in group B only 15 children responded to monotherapy. At the end of follow-up, the percentage of seizure-free patients was significantly higher in group A than in group B. CONCLUSIONS: Childhood occipital epilepsy of Gastaut has an overall favourable prognosis and a good response to antiepileptic therapy with resolution of seizures and of electroencephalogram abnormalities. The association of typical COE-G symptoms with other types of seizure could be related to a poor epilepsy outcome.

Spiral formation at the microscale by µ-pyro-electrospinning.

Spiral shapes occur frequently in nature as in the case of snail shells or the cochlea - the auditory portion of the inner ear. They also inspire many technological devices that take advantage of this geometry. Here we show that µ-pyro-electrospinning is able to control whipping instabilities in order to form spiralling fibres (down to 300 nm thick) directly on a support with true microscale regularity. The results show that polymer concentration plays a key role in producing reliable and long spirals. We investigate the cell response to these spiral templates that, thanks to their true regularity, would be useful for developing innovative cochlea regeneration scaffolds.

Brain anatomical substrates of mirror movements in Kallmann syndrome.

Among male patients affected by Kallmann syndrome, a genetically determined disease due to defective neural migration leading to hypogonadropic hypogonadism and hypo/anosmia, about 40% present the peculiar phenomenon of mirror movements, i.e. involuntary movements mirroring contralateral voluntary hand movements. Several pathogenic hypotheses have been proposed, but the ultimate neurological mechanisms are still elusive. The aim of the present study was to investigate brain anatomical substrates of mirror movements in Kallmann syndrome by means of a panel of quantitative MRI analyses. Forty-nine male Kallmann syndrome patients underwent brain MRI. The study protocol included 3D-T1-weighted gradient echo, fluid attenuated inversion recovery and diffusion tensor imaging. Voxel-based morphometry, sulcation, curvature and cortical thickness analyses and tract based spatial statistics were performed using SPM8, Freesurfer and FSL. All patients underwent a complete physical and neurological examination including the evaluation of mirror movements (according to the Woods and Teuber criteria). Kallmann syndrome patients presenting with mirror movements (16/49, 32%) displayed the following brain changes: 1) increased gray matter density in the depth of the left precentral sulcus behind the middle frontal gyrus; 2) decreased cortical thickness in the precentral gyrus bilaterally, in the depth of right precentral sulcus and in the posterior portion of the right superior frontal gyrus; and 3) decreased fractional anisotropy in the left hemisphere involving the temporal lobe and peritrigonal white matter. No differences were shown by cortical curvature and sulcation analyses. The composite array of brain changes observed in Kallmann syndrome patients with mirror movements likely represents the anatomical-structural underpinnings leading to the peculiar derangement of the complex circuitry committed to unilateral hand voluntary movements.

Migraine improvement during short lasting ketogenesis: a proof-of-concept study.

BACKGROUND AND PURPOSE: Ketogenesis is a physiological phenomenon due to starvation or a ketogenic diet (KD), a drastic restricted carbohydrate dietary regimen that induces lipid metabolism and ketone body synthesis. Two patients whose migraines disappeared only during, and not outside, cycles of very-low-calorie KD performed to reduce their weight were recently observed. To confirm our observation, in a dietitian clinical setting two parallel groups of migraineurs, one receiving a 1-month very-low-calorie KD prescription followed by a 5-month standard low-calorie diet (SD) and the other a 6-month SD, were followed. METHODS: Ninety-six overweight female migraineurs were enrolled in a diet clinic and blindly received a KD (n = 45) or an SD (n = 51) prescription. Mean monthly attack frequency, number of days with headaches and tablet intake were assessed before and 1, 2, 3 and 6 months after diet initiation. RESULTS: In the KD group, the baseline attack frequency (2.9 attacks per month), number of days with headaches (5.11 days per month) and tablet intake (4.91 doses per month) were significantly reduced after the first month of diet (respectively 0.71, 0.91, 0.51; overall, KD versus baseline, P < 0.0001). During the transition period (first versus second month), the KD group showed a transient worsening of each clinical headache variable (respectively 2.60, 3.60, 3.07), despite being improved compared with baseline, with continuous improvement up to month 6 (respectively 2.16, 2.78, 3.71). In the SD group, significant decreases in the number of days with headaches and tablet intake were observed only from month 3 (P < 0.0001), and in attack frequency at month 6 (P < 0.0001). CONCLUSIONS: The underlying mechanisms of KD efficacy could be related to its ability to enhance mitochondrial energy metabolism and counteract neural inflammation.

Possible role of perineal ultrasound in the diagnosis of cystocele.

OBJECTIVE: Perineal ultrasound has not yet been adequately evaluated in relation to the diagnosis of anatomical descensus of pelvic organs. Therefore, the aim of the present study was to assess whether it is possible to carry out a topographical comparison between bladders in normal seat and prolapsed ones and to quantify the extent of descensus. MATERIALS AND METHODS: The authors selected 140 women, divided into three groups (two control groups and one case group). All patients underwent urogynaecological examination, according to the Pelvic Organ Prolapse Quantification (POP-Q), and perineal ultrasound to evaluate pubo-bladder distance. RESULTS: Considering the data recorded in the two control groups, the authors established the physiological pubo-bladder distance between 27-33 mm at rest and 25-30 mm under stress. In the group with cystocele, the pubo-bladder distance was significantly lower: 20 mm at rest and three mm under stress (mean value). The authors also performed a classification of ultrasound cystocele in four stages, in accordance with clinical staging. CONCLUSIONS: In conclusion, the present data show the excellent potential role of perineal ultrasound in the diagnosis of cystocele, but it is necessary to perform randomized studies to standardize the method.

Dynamic changes in thalamic microstructure of migraine without aura patients: a diffusion tensor magnetic resonance imaging study.

BACKGROUND AND PURPOSE: The thalamus seems to be profoundly involved in the cyclical recurrence of migraine clinical and neurophysiological features. Here possible structural changes in the thalamus of migraineurs were searched for by means of diffusion tensor (DT) magnetic resonance imaging (MRI). This MRI technique provides quantitative data on water molecule motion as a marker of tissue microstructure. METHODS: Twenty-four untreated migraine without aura (MO) patients underwent DT-MRI scans (3-T Siemens Gyroscan) during (n = 10) and between attacks (n = 14) and were compared with a group of 15 healthy volunteers (HVs). Fractional anisotropy (FA) and mean diffusivity (MD) were examined. RESULTS: During the interictal phase MO patients had a significantly higher FA and slightly lower MD values in bilateral thalami compared with HVs. During attacks, all MRI quantitative measurements in migraineurs were similar to those found in HVs. Right thalamic FA was positively correlated with the number of days since the last migraine attack in pooled patient data (r = 0.626, P = 0.003). CONCLUSIONS: These higher thalamic FA values noted during the interictal period which normalized during an attack are probably related to plastic peri-ictal modifications in regional branching and crossing of fibres. Whether these changes could be considered as the anatomical counterpart of the cyclical functional fluctuations previously observed in the neurophysiology of migraine remains to be determined.

Efficacy and tolerability of add-on lacosamide in children with Lennox-Gastaut syndrome.

OBJECTIVE: Available data on the efficacy of lacosamide in children with Lennox-Gastaut syndrome (LGS) are scarce and controversial. We present our experience with lacosamide therapy in children affected by LGS. MATERIAL AND METHODS: Medical charts of all children affected by LGS receiving oral lacosamide adjunctive therapy in six paediatric neurology centres were retrospectively evaluated. Efficacy was determined according to the frequency of countable seizures during the 4 weeks prior to treatment and the frequency in the last 4 weeks of observation. Patients whose seizure frequency was reduced by at least 50% were defined as responders. RESULTS: Eighteen children (mean age 12.3 years) were identified. After a mean follow-up period of 9 months, 33% of patients were responders. None of them was seizure-free during the study period. The overall seizure reduction rate was 29%. The percentage reductions from baseline in tonic seizures and drop-attacks rates were 31% and 20%, respectively. Adverse reactions occurred in 44% of patients. The drug was discontinued in four (22%) patients because of increased seizure frequency (three cases) and walking instability (another patient). CONCLUSIONS: A third of children with LGS were responders after lacosamide adjunctive therapy. Although caution is still necessary when the drug is used in children with LGS, our preliminary observations suggest that lacosamide might be effective and represent a possible therapeutic option in children affected by LGS.

Anticonvulsant drugs and hematological disease.

Many antiepileptic drugs (AEDs) are associated with hematological disorders that range from mild thrombocytopenia or neutropenia to anemia, red cell aplasia, until bone marrow failure. Fortunately, potentially fatal hematological disorders such as aplastic anemia are very rare. This review investigates hematological effects associated with classic and newer AEDs: a PubMed search indexed for MEDLINE was undertaken to identify studies in adults, children and animals using the name of all anticonvulsant drugs combined with the terms "hematological disease" and "hematological abnormalities" as key words. The most common hematological alterations occur with older AEDs than newer. Indeed, careful hematological monitoring is needed especially using carbamazepine, phenytoin and valproic acid. The pathogenetic mechanisms are still unknown: they seem to be related to an immunological mechanism, but drugs pharmacokinetics and pharmacodynamics interactions may also play an important role. Further research is needed to assess the real pathogenetic mechanism at the basis of hematological complications caused by AEDs.

Digital holographic microscopy for the evaluation of human sperm structure.

The morphology of the sperm head has often been correlated with the outcome of in vitro fertilization, and has been shown to be the sole parameter in semen of value in predicting the success of intracytoplasmic sperm injection and intracytoplasmic morphologically selected sperm injection. In this paper, we have studied whether digital holographic microscopy (DHM) may be useful to obtain quantitative data on human sperm head structure and compared this technique with high-power digitally enhanced Nomarski optics. The main advantage of digital holography is that high-resolution three-dimensional quantitative sample imaging may be automatically produced by numerical refocusing of a two-dimensional image at different object planes without any mechanical scanning. We show that DHM generates useful information on the dimensions and structure of human sperm, not revealed by conventional phase-contrast microscopy, in particular the volume of vacuoles, and suggest its use as an additional prognostic tool in assisted reproduction technology.

Asymmetric MSM sub-bandgap all-silicon photodetector with low dark current.

Design, fabrication, and characterization of an asymmetric metal-semiconductor-metal photodetector, based on internal photoemission effect and integrated into a silicon-on-insulator waveguide, are reported. For this photodetector, a responsivity of 4.5 mA/W has been measured at 1550 nm, making it suitable for power monitoring applications. Because the absorbing metal is deposited strictly around the vertical output facet of the waveguide, a very small contact area of about 3 µm2 is obtained and a transit-time-limited bandwidth of about 1 GHz is demonstrated. Taking advantage of this small area and electrode asymmetry, a significant reduction in the dark current (2.2 nA at -21 V) is achieved. Interestingly, applying reverse voltage, the photodetector is able to tune its cut-off wavelength, extending its range of application into the MID infrared regime.

Surface plasmon resonance optical cavity enhanced refractive index sensing.

We report on a method for surface plasmon resonance (SPR) refractive index sensing based on direct time-domain measurements. An optical resonator is built around an SPR sensor, and its photon lifetime is measured as a function of loss induced by refractive index variations. The method does not rely on any spectroscopic analysis or direct intensity measurement. Time-domain measurements are practically immune to light intensity fluctuations and thus lead to high resolution. A proof of concept experiment is carried out in which a sensor response to liquid samples of different refractive indices is measured. A refractive index resolution of the current system, extrapolated from the reproducibility of cavity-decay time determinations over 133 s, is found to be about 10(-5) RIU. The possibility of long-term averaging suggests that measurements with a resolution better than 10(-7) RIU/√Hz are within reach.