Intracranial complications of sinogenic and otogenic infections in children: an ESPN survey on their occurrence in the pre-COVID and post-COVID era.

BACKGROUND: COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are the intracranial complications of sinusitis and otitis (ICSO). According to some studies on a limited number of cases, both streptococci-related sinusitis and ICSO would have increased immediately after the pandemic, although the reason is not clear yet (seasonal changes versus pandemic-related effects). The goal of the present survey of the European Society for Pediatric Neurosurgery (ESPN) was to collect a large number of cases from different European countries encompassing the pre-COVID (2017-2019), COVID (2020-2021), and post-COVID period (2022-June 2023) looking for possible epidemiological and/or clinical changes. MATERIAL AND METHODS: An English language questionnaire was sent to ESPN members about year of the event, patient's age and gender, presence of immune-deficit or other favoring risk factors, COVID infection, signs and symptoms at onset, site of primary infection, type of intracranial complication, identified germ, type and number of surgical operations, type and duration of medical treatment, clinical and radiological outcome, duration of the follow-up. RESULTS: Two hundred fifty-four cases were collected by 30 centers coming from 14 different European countries. There was a statistically significant difference between the post-COVID period (129 children, 86 cases/year, 50.7% of the whole series) and the COVID (40 children, 20 cases/year, 15.7%) or the pre-COVID period (85 children, 28.3 cases/year, 33.5%). Other significant differences concerned the presence of predisposing factors/concurrent diseases (higher in the pre-COVID period) and previous COVID infection (higher in the post-COVID period). No relevant differences occurred as far as demographic, microbiological, clinical, radiological, outcome, morbidity, and mortality data were concerned. Paranasal sinuses and middle ear/mastoid were the most involved primary site of infection (71% and 27%, respectively), while extradural or subdural empyema and brain abscess were the most common ICSO (73% and 17%, respectively). Surgery was required in 95% of cases (neurosurgical and ENT procedure in 71% and 62% of cases, respectively) while antibiotics in 99% of cases. After a 12.4-month follow-up, a full clinical and radiological recovery was obtained in 85% and 84% of cases, respectively. The mortality rate was 2.7%. CONCLUSIONS: These results suggest that the occurrence of ICSO was significantly increased after the pandemic. Such an increase seems to be related to the indirect effects of the pandemic (e.g., immunity debt) rather than to a direct effect of COVID infection or to seasonal fluctuations. ICSO remain challenging diseases but the pandemic did not affect the management strategies nor their prognosis. The epidemiological change of sinusitis/otitis and ICSO should alert about the appropriate follow-up of children with sinusitis/otitis.

Blood-brain barrier damage associates with glia-related cytokines in the cerebrospinal fluid of patients with Multiple Sclerosis.

BACKGROUND: The presence of Blood-Brain Barrier (BBB) dysfunction is defined by albumin quotient (QALB) and characterize a group of Multiple Sclerosis (MS) patients at clinical onset. We evaluated the concentration in cerebrospinal fluid (CSF) of 87 cytokines, to better characterize the CSF inflammatory pattern in presence of BBB damage. MATERIALS AND METHOD: In an exploratory cohort, CSF cytokines were evaluated by means of Multiplex technology (Bio-Plex Pro-Human Cytokine, GF and Diabetes 27-Plex Panel, Bio-Plex Pro-Human Chemokines 40-Plex Panel, Bio-Plex Pro-Human Inflammation Assays 37-Plex Panel) in a cohort of Other Not Inflammatory Neurological Disorders (ONIND) and in cohort of patients with MS, stratified according to BBB damage into QALB+ and QALB- MS patients. In the validation cohort, we evaluated the relevant molecules in a cohort of MS patients, stratified again into QALB+ and QALB-, including also Neurofilament Light (NfL) and Chitinase 3-like 1 (CHI3L1) CSF concentration. RESULTS: While MIP-1α, CXCL-13, and CCL-22 CSF concentrations were higher in both MS groups compared to ONIND, in QALB+ MS CSF concentrations of CXCL-9 (17.85 ± 4.69 pg/mL), CXCL-10 (476.5 ± 324.3 pg/mL), and IL-16 (96.08 ± 86.17 pg/mL) were higher than in QALB- MS (8.98 ± 5368 pg/mL, p < 0.005, 281.0 ± 180.9 pg/mL, p < 0.05, and 47.35 ± 36.87 pg/mL, p < 0.005, respectively) and ONIND (8.98 ± 5368 pg/mlL, p < 0.005, 281.0 ± 180.9 pg/mL, p < 0.005, and 47.35 ± 36.87 pg/mL, p < 0.001, respectively). A strong correlation was observed between CXCL-9 and CXCL-10 in all MS groups (all r>0.75, all p < 0.001). In the validation cohort again CXCL-10 CSF concentration were higher in QALB+ MS than in QALB- MS (94.25 ± 64.75 vs 153.8 ± 99.52, p < 0.05), while no difference was observed in serum. CSF NfL (1642 ± 1963 vs 3231 ± 3492 pg/mL, p < 0.05) and CHI3L1 (183.9 ± 86.62 vs 262 ± 137.5 ng/mL, p < 0.05) were increased in QALB+ MS. CONCLUSIONS: BBB damage in MS is linked to a specific CSF cytokines pattern (CXCL-9, CXCL-10, IL-16), that are also involved in astrocyte-microglia interaction. To what extent their continuous production in the CNS may mark a more severe disease course merits to be investigated.

Supercooled solutions of sodium perchlorate in TIP4P/2005 water: The effect of martian solutes on thermodynamics and structure.

We study the thermodynamic behavior of sodium perchlorate solutions in supercooled water through molecular dynamics numerical simulations. These solutions are of special interest because of the recent experimental results that led to hypothesize the presence of liquid water in perchlorate solutions beneath the Martian soil. We model water using the TIP4P/2005 potential. The results we obtain for solutions with concentrations 1.63 and 15.4 wt% are in agreement with those of a system undergoing a liquid-liquid phase transition where the liquid-liquid critical point shifts to slightly higher temperatures and lower pressures. The structure of the system is also analyzed, and we come to the conclusion that, even at the highest concentration considered, water retains its anomalous behavior.

The Communicative-Relational Operating Model of the Italian National Institute of Health for an Effective Telephone Intervention in Public Health, Structured on Basic Counselling Skills.

Introduction: Communication has a crucial role in public health, because it becomes an essential component of prevention; it is also a proactive tool in health promotion. From a planning perspective, it is appropriate to use communication means that can help the bidirectional communication process, such as face-to-face communication and telephone communication. Materials and methods: In relation to this, the Italian National Institute of Health has developed the "Modello Operativo Comunicativo-Relazionale" (the "Communicative-Relational Operating Model"). It is based on the fundamental skills of the counselling, this gives a protocol to the health professionals that is replicable and organized and it allows health professionals to carry out a telephone communication that is efficient with the user through technical-scientific and communication-relational skills. The goal is to answer in a customized way to the various users' health needs. The Operating Model was created by experts of the National AIDS and Sexually Transmitted Infections Helpline of the Operational Unit of Psycho-Socio-Behavioural Research, Communication, Training, of the Infectious Diseases Department. Later, the Operating Model was proposed to the experts of the Helplines in the National Centre on Addictions and Doping and the National Helpline of the National Centre for Rare Diseases in the National Institute of Health that integrated this method into their telephone approach. Results: The Operating Model illustrated above was applied to several helplines of the National Institute of Health as an example of correct scientific information, updated and customized on sexual transmitted infections, addictions and rare diseases. Conclusions: This article aims to illustrate the Operating Model, the theoretical prerequisites that subtend it and its possible application in the different public health structures that use the telephone for a profes-sional relationship with their users.

Survey on the interest and commitment of AIFM members to scientific activities (SicAS) - The initiative of the FutuRuS working group.

PURPOSE: The "FutuRuS" working group of the Italian Association of Medical Physics and Health Physics (AIFM) designed a survey (SicAS) to get feedback from its members regarding their interests and their experience in taking part in scientific activities and events, with the objective of focusing future efforts of the AIFM towards increasing the scientific activity of the medical physics expert (MPE). METHODS: SicAS was sent out in March 2022 to all AIFM members by newsletter and official communication. SicAS was structured into three sections: personal information and institution of affiliation information, involvement in scientific activities, interest in and commitment to scientific activities. Responses were collected in a fully anonymised mode from the Google Forms platform and analysed with descriptive statistics. RESULTS: Out of 1289 members (active at the end of 2021), 467 responded to the Survey (response rate of 36%). The Survey results highlighted that AIFM members ranked the involvement of the MPE in scientific activities as highly relevant to the profession. However, 34.7% indicated devoting less than 10% of their working time to scientific activities. 67.5% of the respondents were dissatisfied with the time spent on scientific activities. The primary barrier was the lack of time (77%), followed by a lack of mentoring (32%). CONCLUSIONS: SicAS highlighted the need for AIFM initiatives to support members' scientific activities. National societies should help develop and support networks between members, create links among universities, hospitals, research institutions and industries, and provide guidelines and learning platforms for enhancing the MPEs' involvement in scientific activities.

New treatments for multidrug-resistant non-fermenting Gram-negative bacilli Infections.

Ceftolozane/tazobactam, ceftazidime/avibactam and cefiderocol belong to a novel generation of antibiotics that correspond with the ß-lactam family. It is necessary to having new options in treating infections caused by Gram-negative, non-fermenting multidrug-resistant bacilli due to the significant increase in multidrug resistance in the last decades. Knowing the main characteristics of each drug is key for correct use.

Multiple sclerosis epidemiological trends in Italy highlight the environmental risk factors.

Italy is definitely a high-risk country for multiple sclerosis (MS). Over the last 50 years, several epidemiological studies, including longitudinal surveys, have disclosed that MS incidence and prevalence in Italy mainland and Islands (Sardinia and Sicily) have progressively increased, picturing a semi-parabolic curve. Based on the comprehensive scrutiny of 58 papers, we conclude that the latitude risk gradient does not fit to the Italian map of MS. The genetic heterogeneity of the Italian ethnicities, that likely forms the basis of MS predisposition, does not account for the dramatic increase of MS incidence and prevalence observed in Italy over the last half century that, rather, seems better explained by the effect of environmental factors.

Spontaneous NaCl-doped ices Ih, Ic, III, V and VI. Understanding the mechanism of ion inclusion and its dependence on the crystalline structure of ice.

Direct coexistence simulations on a microsecond time scale have been performed for different types of ice (Ih, Ic, III, V, and VI) in contact with a NaCl aqueous solution at different pressures. In line with the previous results obtained for ice Ih [Conde et al., Phys. Chem. Chem. Phys., 2017, 19, 9566-9574], our results reveal the spontaneous growth of a new ice doped phase and the formation of a brine rejection phase in all ices studied. However, both the preferential incorporation of ions into the ice lattice and the inclusion mechanisms depend on the crystalline structure of each ice. This work shows the inclusion of Cl- and Na+ ions in ice from salt using molecular dynamics simulation, in agreement with the experimental evidence found in the literature. The model used for water is TIP4P/2005. For NaCl we employ a set of potential parameters that uses unit charges for the ions.

Delayed recurrence of spontaneous intracranial hypotension syndrome mimicking a Chiari I malformation: Case report with a review of the literature.

INTRODUCTION: Cerebellar tonsils descent seen on brain MRI is, along with other findings, a recognized radiological sign of possible spontaneous intracranial hypotension (SIH). The short-term outcome of SIH is usually favorable with symptoms improvement and reversibility of the low-lying tonsils. Nevertheless, data on the long-term outcome are lacking or inconsistent. CASE REPORT: A 32-year-old woman presented to her general practitioner with a six months history of non-specific headaches. An MRI brain with gadolinium showed a 12mm tonsillar descent with no other remarkable findings. Headaches were initially managed conservatively as migraines. Following the onset of progressive upper back and shoulder pain at rest, nausea, photophobia and fogging in her vision, the patient was referred to our Department with a suspicion of symptomatic Chiari I malformation. After an in-depth anamnesis, it emerged a previous history of SIH, 14 years earlier, successfully treated conservatively in another center. A whole spine MRI confirmed the suspicion of recurrent SIH showing an anterior cervico-thoracic epidural fluid collection. The patient underwent an epidural blood patch with complete resolution of the symptoms and radiological signs. DISCUSSION: To our knowledge, this case is the first report of delayed recurrence of a SIH successfully treated conservatively over 10 years earlier. The etiopathogenesis and management of this rarity with literature review is discussed. CONCLUSION: An isolated cerebellar tonsil descent with no other remarkable findings on brain MRI and a previous history of SIH should always alert the clinician of a possible late recurrence of a CSF leak and avoid unnecessary Chiari I malformation surgical procedures.

Characterization of hydration water in supercooled water-trehalose solutions: The role of the hydrogen bonds network.

The structural and dynamical properties of hydration water in aqueous solutions of trehalose are studied with molecular dynamics simulation. We simulate the systems in the supercooled region to investigate how the interaction with the trehalose molecules modifies the hydrogen bond network, the structural relaxation, and the diffusion properties of hydration water. The analysis is performed by considering the radial distribution functions, the residence time of water molecules in the hydration shell, the two body excess entropy, and the hydrogen bond water-water and water-trehalose correlations of the hydration water. The study of the two body excess entropy shows the presence of a fragile to strong crossover in supercooled hydration water also found in the relaxation time of the water-water hydrogen bond correlation function, and this is in agreement with predictions of the mode coupling theory and of previous studies of the oxygen-oxygen density correlators [A. Iorio et al., J. Mol. Liq. 282, 617 (2019); Sci. China: Phys., Mech. Astron. 62, 107011 (2019)]. The water-trehalose hydrogen bond correlation function instead evidences a strong to strong crossover in the relaxation time, and this crossover is related to a trehalose dynamical transition. This signals the role that the strong interplay between the soluted molecules and the surrounding solvent has in determining the dynamical transition common to both components of the system that happens upon cooling and that is similar to the well known protein dynamical transition. We connect our results with the cryoprotecting role of trehalose molecules.

Clinical deterioration despite syringomyelia resolution after successful foramen magnum decompression for Chiari malformation - Case series.

INTRODUCTION: Neurosurgical treatment is recommended for symptomatic syringomyelia and the post-operative radiological resolution of the syringomyelia is associated with an improvement or at least stability of the patient's pre-operative symptoms. METHODS: We reviewed syringomyelia treatment in our centre over the last five years for clinical outcome, surgical complications, post operative MRI and long term symptom resolution. RESULTS: 50 cases of symptomatic syringomyelia underwent foramen magnum decompression and expansile watertight duroplasty. While the outcomes for majority are similar to what published in literature, three of them developed typical syringomyelia symptoms after initial good recovery and radiological resolution of syrinx. CONCLUSION: Syringomyelia symptoms may appear or worsen following successful surgical treatment and radiological resolution of syrinx and it is important to counsel young people and their family regarding this.

Evidence of Incoherent Carriers Associated with Resonant Impurity Levels and Their Influence on Superconductivity in the Anomalous Superconductor Pb_{1-x}Tl_{x}Te.

We present a combined experimental and theoretical study of the evolution of the Fermi surface of the anomalous superconductor Pb_{1-x}Tl_{x}Te as a function of thallium concentration, drawing on a combination of magnetotransport measurements (Shubnikov-de Haas oscillations and the Hall coefficient), angle resolved photoemission spectroscopy, and density functional theory calculations of the electronic structure. Our results indicate that for Tl concentrations beyond a critical value, the Fermi energy coincides with resonant impurity states in Pb_{1-x}Tl_{x}Te, and we rule out the presence of an additional valence band maximum at the Fermi energy. A comparison to nonsuperconducting Pb_{1-x}Na_{x}Te implies that the presence of these impurity states at the Fermi energy provides the enhanced pairing interaction and thus also the anomalously high temperature superconductivity in this material.

Intrathecal K free light chain synthesis in multiple sclerosis at clinical onset associates with local IgG production and improves the diagnostic value of cerebrospinal fluid examination.

BACKGROUND: The pathological significance and the diagnostic usefulness of intrathecal κ and λ free light chain (FLC) synthesis in Multiple Sclerosis (MS) are debated. METHODS: Paired cerebrospinal fluid (CSF) and serum specimens from 70 relapsing remitting MS (RRMS), 40 with and 30 without CSF restricted IgG Oligoclonal Band (IgGOB), and 37 from healthy controls (HC) were analyzed. IgG, IgM, κFLC and λFLC concentrations and indexes were evaluated. All RRMS performed MRI to estimate white and grey matter (WM) pathology. RESULTS: In HC, no intrathecal κ or λ FLC synthesis was found, and κFLC and λFLC Indexes were reciprocally correlated (r = 0.67, p < 0.001). In RRMS, intrathecal κFLC or λFLC synthesis was demonstrated in respectively 66% and 43% of the cases, the Qκ/λ ratio was significantly higher compared to HC (17.0 ±â€¯31.3 vs 0.79 ±â€¯0.20, p < 0.001) and the correlation between κFLC Index and λFLC Index was weak (r:0.38, p < 0.05). Intrathecal IgG synthesis was associated with κFLC Index (IgG Index: r2 = 0.53, ß = 0.73, p < 0.001; IgGLOC: r2 = 0.37, ß = 0.61, p < 0.001; IgGIF: r2 = 0.69, ß = 0.83, p < 0.001), but not with λFLC Index, while intrathecal IgM synthesis correlated with λFLC Index (IgM Index: r = 0.41, p < 0.001; IgMLOC: r = 0.34, p < 0.005; IgMIF: r = 0.45, p < 0.001), but not with κFLC Index. 26% of RRMS patients without CSF-restricted IgGOB had increased κFLCLOC. Finally, no associations were observed between any CSF and MRI parameters. CONCLUSIONS: The demonstration of intrathecal κFLC synthesis may further improve the diagnostic usefulness of CSF examination in RRMS. The marked increased in Qκ/λ further suggests a deregulated B-cell activation in MS pathology.

Scale-invariant magnetoresistance in a cuprate superconductor.

The anomalous metallic state in the high-temperature superconducting cuprates is masked by superconductivity near a quantum critical point. Applying high magnetic fields to suppress superconductivity has enabled detailed studies of the normal state, yet the direct effect of strong magnetic fields on the metallic state is poorly understood. We report the high-field magnetoresistance of thin-film La2-x Sr x CuO4 cuprate in the vicinity of the critical doping, 0.161 ≤ p ≤ 0.190. We find that the metallic state exposed by suppressing superconductivity is characterized by magnetoresistance that is linear in magnetic fields up to 80 tesla. The magnitude of the linear-in-field resistivity mirrors the magnitude and doping evolution of the well-known linear-in-temperature resistivity that has been associated with quantum criticality in high-temperature superconductors.

High density liquid structure enhancement in glass forming aqueous solution of LiCl.

We investigate using molecular dynamics simulations the dynamical and structural properties of LiCl:6H2O aqueous solution upon supercooling. This ionic solution is a glass forming liquid of relevant interest in connection with the study of the anomalies of supercooled water. The LiCl:6H2O solution is easily supercooled and the liquid state can be maintained over a large decreasing temperature range. We performed simulations from ambient to 200 K in order to investigate how the presence of the salt modifies the behavior of supercooled water. The study of the relaxation time of the self-density correlation function shows that the system follows the prediction of the mode coupling theory and behaves like a fragile liquid in all the range explored. The analysis of the changes in the water structure induced by the salt shows that while the salt preserves the water hydrogen bonds in the system, it strongly affects the tetrahedral hydrogen bond network. Following the interpretation of the anomalies of water in terms of a two-state model, the modifications of the oxygen radial distribution function and the angular distribution function of the hydrogen bonds in water indicate that LiCl has the role of enhancing the high density liquid component of water with respect to the low density component. This is in agreement with recent experiments on aqueous ionic solutions.

Freezing Temperatures, Ice Nanotubes Structures, and Proton Ordering of TIP4P/ICE Water inside Single Wall Carbon Nanotubes.

A very recent experimental paper importantly and unexpectedly showed that water in carbon nanotubes is already in the solid ordered phase at the temperature where bulk water boils. The water models used so far in literature for molecular dynamics simulations in carbon nanotubes show freezing temperatures lower than the experiments. We present here results from molecular dynamics simulations of water inside single walled carbon nanotubes using an extremely realistic model for both liquid and icy water, the TIP4P/ICE. The water behavior inside nanotubes of different diameters has been studied upon cooling along the isobars at ambient pressure starting from temperatures where water is in a liquid state. We studied the liquid/solid transition, and we observed freezing temperatures higher than in bulk water and that depend on the diameter of the nanotube. The maximum freezing temperature found is 390 K, which is in remarkable agreement with the recent experimental measurements. We have also analyzed the ice structure called "ice nanotube" that water forms inside the single walled carbon nanotubes when it freezes. The ice forms observed are in agreement with previous results obtained with different water models. A novel finding, a partial proton ordering, is evidenced in our ice nanotubes at finite temperature.

Anomalous relaxation kinetics and charge-density-wave correlations in underdoped BaPb1-x Bi x O3.

Superconductivity often emerges in proximity of other symmetry-breaking ground states, such as antiferromagnetism or charge-density-wave (CDW) order. However, the subtle interrelation of these phases remains poorly understood, and in some cases even the existence of short-range correlations for superconducting compositions is uncertain. In such circumstances, ultrafast experiments can provide new insights by tracking the relaxation kinetics following excitation at frequencies related to the broken-symmetry state. Here, we investigate the transient terahertz conductivity of BaPb1-x Bi x O3--a material for which superconductivity is "adjacent" to a competing CDW phase--after optical excitation tuned to the CDW absorption band. In insulating BaBiO3 we observed an increase in conductivity and a subsequent relaxation, which are consistent with quasiparticles injection across a rigid semiconducting gap. In the doped compound BaPb0.72Bi0.28O3 (superconducting below TC = 7 K), a similar response was also found immediately above TC This observation evidences the presence of a robust gap up to T [Formula: see text] 40 K, which is presumably associated with short-range CDW correlations. A qualitatively different behavior was observed in the same material for [Formula: see text] 40 K. Here, the photoconductivity was dominated by an enhancement in carrier mobility at constant density, suggestive of melting of the CDW correlations rather than excitation across an optical gap. The relaxation displayed a temperature-dependent, Arrhenius-like kinetics, suggestive of the crossing of a free-energy barrier between two phases. These results support the existence of short-range CDW correlations above TC in underdoped BaPb1-x Bi x O3, and provide information on the dynamical interplay between superconductivity and charge order.