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Abstract: The effects of the nuclear reaction 10B(n, α)7Li on the properties and structure of a sodium borosilicate glass were analysed by density, hardness and fracture toughness measurements, Raman and Nuclear Magnetic Resonance spectroscopy and Transmission Electronic Microscopy (TEM) characterization. The TEM observations showed a homogeneous irradiated glass structure up to the nanometer scale. Modifications of the local order around the main cations were noticed, mainly a slight decrease of the mean boron coordination number and an increase of non-bridging oxygen concentrations. At the glass medium range order, the appearance of the D2 Raman band and a modification of the Si–O–Si angle distribution were also observed after irradiation. A comparison with other irradiation conditions with Swift Heavy Ions (Kr with 74MeV) and Gold irradiation (with energies ranging from 1 to 7MeV) is presented. Raman spectroscopy showed a similar final structure for irradiation conditions under which the glass evolutions are controlled by electronic energy loss in the ion tracks formation regime or nuclear energy loss. Despite important differences in energy deposition regimes, the similarities observed between the final glass structures suggest that structural evolutions are controlled by the glass relaxation mechanisms during the high quenching rate step that follows the energy deposition step. [Copyright &y& Elsevier]

Abstract: A defect formation mechanism is proposed in order to explain recently observed Raman defect lines on He2+ irradiated UO2. These defects are formed by electronic stopping of He2+ even though their dE/dx is less than the threshold for track formation. Referring to literature of self-trapped excitons, this mechanism is divided in three steps: creation of electronic defects by electron stopping, stabilization of self-trapped excitons on uranium sublattice and, after accumulation of self-trapped excitons, formation of structural defect on the oxygen sublattice. This proposed mechanism still needs to be validated by more experimental evidence of the Magneli type defect proposed to be the self-trapped excitons on uranium lattice. [Copyright &y& Elsevier]

Background: Alternating hemiplegia of childhood (AHC) is a rare disorder with both neurologic and cardiac manifestations. The ATP1A3-D801N variant is associated with a pathologically short QT interval and risk of ventricular arrhythmia following bradycardia; however, the mechanism of this remains unknown. We investigated the relationship between heart rate (HR), QT, and QTc, hypothesizing that individuals with ATP1A3-D801N have abnormal, impaired shortening of QT and QTc at lower HR leading to arrhythmia predisposition., Methods: We performed a retrospective observational study of individuals who underwent clinical evaluation, Holter monitoring, and genetic testing for AHC at Duke University Hospitals. We also compiled a group of healthy individuals as a control cohort. A larger, worldwide cohort of individuals with ATP1A3 -related phenotypes was compiled to investigate sinus node dysfunction. Linear regression analysis was then performed., Results: The cohort consisted of 44 individuals with ATP1A3 -related phenotypes with 81 Holter recordings (52.27% female; mean age at first Holter 8.04 years, range 0.58 - 33 years), compared to 36 healthy individuals with 57 Holter recordings (52.78% female; mean age at first Holter 9.84 years, range 0.08 - 38 years). Individuals with ATP1A3-D801N had reduced prolongation of QT at lower HR, manifest as a significantly lower slope for HR vs QT compared to healthy (P<0.0001). This resulted in a significantly higher slope of the relationship for HR vs QTc compared to healthy (P<0.0001). Individuals with ATP1A3 -related phenotypes and baseline QTc <350 milliseconds (ms) had increased shortening of QT and QTc at lower HR compared to those with normal QTc (P=0.003; P=0.001). Among worldwide cases, 3 out of 131 individuals with ATP1A3 -related phenotypes required device implantation and/or had sinus pauses >4 seconds., Conclusions: Individuals with the ATP1A3-D801N variant exhibit paradoxical shortening of QT and QTc at lower HR, which contributes to an increased risk of arrhythmias during bradycardia. This is exacerbated by an underlying risk of sinus node dysfunction., Clinical Perspective: What is Known:Individuals with ATP1A3-D801N have a short baseline QTc.Two individuals with AHC experienced ventricular fibrillation following bradycardia.What the Study Adds:The QT and QTc shorten to a greater extent at lower heart rate in individuals with ATP1A3-D801N than in healthy individuals. Individuals with ATP1A3 -related phenotypes and QTc <350ms show greater impairment of QT and QTc dynamics than those with normal QTc. There is low prevalence of device implantation and significant sinus pauses in individuals with ATP1A3 -related phenotypes, with a relatively greater prevalence in those with ATP1A3-D801N.

Developmental and epileptic encephalopathies (DEEs) are severe forms of epilepsy characterized by seizure onset in infancy or childhood. The seizures are typically drug-resistant and often accompanied by significant alterations in the electroencephalogram (EEG). DEEs are associated with neurodevelopmental impairment, which can arise from both the epileptic activity itself and the underlying etiology, which is most often genetic in origin. We present the clinical and molecular features of two patients with DEE associated with a pathogenic variant in the UGDH gene. This gene encodes a protein that converts uridine diphosphate (UDP)-glucose into UDP-glucuronate, which plays a crucial role in the biosynthesis of glycosaminoglycans, essential components of the connective tissue and extracellular matrix. Both patients started with epileptic spasms associated with a pattern of hypsarrhythmia in the EEG at 4 months of age. Both developed global developmental delay and the physical examination revealed hypotonia and mildly dysmorphic features. In both families, there was another affected sibling with a similar clinical presentation, although genetic studies were not performed in one of these children. A homozygous pathogenic variant in the UGDH gene, NM&#95;003359.4:c.131C>T - p.(Ala44Val), previously reported to be associated with the described phenotype, was identified., (© 2024 International League Against Epilepsy.)

Background: Severe combined immunodeficiency secondary to adenosine deaminase deficiency is rare. The deficiency of this enzyme results in the accumulation of substrates in the tissues, including the brain. Clinical signs of neurological involvement may include seizures, neurodevelopmental disorders, hypotonia, and sensorineural hearing loss. Hematopoietic stem cell transplantation corrects the failure of the immune system but not the neurological involvement., Objectives: To describe the spectrum of neurological complications identified in a series of children with severe combined immunodeficiency due to adenosine deaminase deficiency. Additionally, we propose a neurological approach including electrophysiological, radiological, and neurocognitive studies to address this group of children in an efficient and timely manner., Methods: A descriptive, observational, retro-, and prospective analysis of patients with a confirmed immunological diagnosis seen between 1996 and 2021 and referred to the Department of Neurology for neurological evaluation was conducted., Results: Ten patients met the inclusion criteria. The median age at diagnosis was 4 months (range, 1-36 months). All patients had neurodevelopmental delay with hypotonia in six, language delay in three, sensorineural hearing loss in four, and spastic paraparesis in one patient. Two children developed an epileptic syndrome, consisting of generalized epilepsy in one and focal epilepsy in the other. Neuroimaging showed brain calcifications in the basal ganglia and/or centrum semiovale in four patients and enlarged subarachnoid spaces in two other patients., Conclusion: In this pediatric series, the rate of neurological involvement associated with abnormalities on neuroimaging was high. Although this involvement could be related to accumulation of adenosine metabolites in the central nervous system, the possibility of associated chronic infections should be ruled out. Given the neurological manifestations, it is important to involve the pediatric neurologist in the multidisciplinary follow-up team., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To determine clinical, electroencephalographic, therapeutic and evolutive characteristics of a series of oncopediatric patients with acute symptomatic seizures., Patients and Methods: We performed a retrospective and prospective descriptive analysis of clinical records of oncopediatric children evaluated by neurology at the comprehensive outpatient Center for Hemato-Oncological Patients during 2017-2021. We included children aged one month to 17 years with intracranial and extracranial tumors who presented with acute symptomatic seizure (ASC). We defined acute symptomatic seizure according to the 2010 International League Against Epilepsy. We classified seizures according to 2017 International League Against Epilepsy classification. We excluded any patient with a diagnosis of previous epilepsy and non-epileptic paroxysmal episodes., Results: We analyzed 44 cases with a median of 4 years (range: 1 month-17 years) and mean of 5.75 months (range: 1 month-11 months) and 8.33 years (2-17 years). The main etiologies were neurotoxicity and post-surgical context. Four patients presented dysnatremias and two associated with endocranial hypertension. Forty-one electroencephalograms were performed with intercritical results with abnormalities in the baseline rhythm, but without foci or paroxysms. There were no critical recordings. Focal seizures were 25 (56.8%) and generalized seizures 19 (43.18%). Levetiracetam was the most commonly used drug for acute management., Conclusions: Our cohort shows that ASC, in this population, do not show considerable differences between focal motor and generalized seizures and occur mostly in neurotoxic and post-surgical contexts. Dysnatremias and endocranial hypertension associated with ASC were also recorded. Postcrisis electroencephalograms were without foci or paroxysms and good seizure evolution.

Objective: The aim of this study was to assess efficacy, safety, and tolerability of highly purified cannabidiol oil (CBD) as add-on therapy for the treatment of a series of patients with infantile epileptic spasms syndrome (IESS) who were resistant to antiseizure medications and ketogenic dietary therapy., Material and Methods: We conducted a retrospective analysis of the medical records of 28 infants with treatment-resistant IESS aged 6 to 21 months who received highly purified CBD between July 2021 and June 2023. Data were collected on neurological examinations, EEG, Video-EEG and polygraphic recordings, imaging studies, laboratory testing, and seizure frequency, type, and duration, and adverse effects. As the primary outcome, a reduction of frequency of epileptic spasms (ES) was assessed. ES freedom was considered after a minimal time of 1 month without ES., Results: Sixteen male and 12 female patients, aged 6-21 months, who received CBD for treatment-resistant IESS were included. The etiology was structural in 10, Down syndrome in seven, genetic in nine, and unknown in two. Initial CBD dose was 2 mg/kg/day, which was uptitrated to a median dose of 25 mg/kg/day (range, 2-50). Prior to CBD initiation, patients had a median of 69 ES in clusters per day (range, 41-75) and of 10 focal seizures per week (range, 7-13). After a mean and median follow-up of 15 and 12.5 months (range, 6-26 months), seven patients were ES free and 12 had a >50 % ES reduction. Five of seven patients (71 %) with Down syndrome and 3/5 (60 %) with cerebral palsy responded well. Adverse effects were mild. EEG improvements correlated with ES reductions., Conclusion: In this study evaluating the use of CBD in children with IESS, 19/28 (67.8 %) had a more than 50 % ES reduction with good tolerability., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest regarding this study., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Dravet syndrome is currently considered as an developmental and epileptic encephalopathy and, recently, mandatory, alert, and exclusionary criteria have been proposed. Here, we describe three patients with Dravet syndrome with the typical early presentation including febrile and afebrile alternating hemiclonic seizures due to loss-of-function SCN1A variants. Subsequently, they developed episodes of febrile focal status epilepticus (SE) associated with hemiparesis and cerebral hemiatrophy with posterior focal seizures, as a consequence of Dravet syndrome. This sequence of events has been previously published in patients with Dravet syndrome and does not contradict the recent classification by the International League Against Epilepsy (ILAE). The ILAE guidance identifies "Focal neurological findings" as alert criteria and "MRI showing a causal focal lesion" as exclusionary criteria for making an initial diagnosis of Dravet syndrome at presentation. Our three patients would correspond to a severe phenotype, similar to the well-known presentation of generalized atrophy following prolonged status epilepticus. Common genetic findings in cases of diffuse and unilateral brain involvement may help explain these clinical presentations. Further genotype-phenotype studies may provide additional insights into this electroclinical behavior., (© 2023 International League Against Epilepsy.)

Importance: Pudendal nerve block has been frequently used as a pain management modality for vaginal prolapse surgery. However, studies investigating its efficacy and the type of anesthetic used have had conflicting results., Objective: This study aimed to evaluate the effect of intraoperative pudendal nerve block with liposomal bupivacaine on postoperative pain after sacrospinous ligament suspension surgery., Study Design: In this single-blinded randomized controlled trial, 83 women undergoing sacrospinous ligament suspension were randomized to receive either intraoperative pudendal nerve block with liposomal bupivacaine or no block. Participants recorded their pain level on postoperative days (PODs) 1-3 and 7, the number of pain medication pills consumed, and the quality of their recovery using a validated questionnaire., Results: There were no significant differences in pain scores between the groups on POD 1 and POD 3: 5 (2-6.25) versus 5.5 (4-8; P = 0.058) and 4 (1-6) versus 5 (2-7; P = 0.146), respectively. On POD 2, the overall pain score was statistically different between the groups, with the block group having lower interquartile ranges. This difference, however, was not clinically significant: 5 (1.75-5) versus 5 (3.25-7.75; P = 0.023). In the subset of participants who underwent a concomitant midurethral sling procedure, POD 2 and POD3 pain scores were significantly lower in those who received the block: 3 (1-5) versus 6 (5-8; P = 0.006) for POD 2 and 3 (1-5) versus 5 (3.250-7; P = 0.042) for POD 3. There were no significant differences in pain medication consumption or the quality of recovery scores., Conclusion: Pudendal nerve block with liposomal bupivacaine did not result in significant differences in postoperative pain after sacrospinous ligament suspension, except in those participants who underwent a concomitant midurethral sling procedure., (Copyright © 2023 American Urogynecologic Society. All rights reserved.)

The identification of factors that affect cannabidiol (CBD) systemic exposure may aid in optimizing treatment efficacy and safety in clinical practice. In this study, we aimed to correlate CBD plasma concentrations at a steady state to demographic, clinical, and pharmacological characteristics as well as seizure frequency after the administration of a purified CBD oil solution in a real-world setting of children with drug-resistant developmental and epileptic encephalopathies (DEEs). Patients receiving oral CBD pharmaceutical products at maintenance were enrolled. Venous blood samples were drawn before the CBD morning dose, 12 h apart from the last evening dose (C0 or CBD trough concentration). A linear mixed-effect analysis was implemented to assess the correlation between C0 and clinical, laboratory, pharmacological, and lifestyle factors. Fifteen females and seven males with a median age of 12.8 years (ranging between 4.7 and 17.2) were included. The median CBD dose was 8.8 mg/kg/day (ranging between 2.6 and 22.5), and the CBD C0 median (range) was 48.2 ng/mL (3.5-366.3). The multivariate model showed a 109.6% increase in CBD C0 in patients with concomitant levothyroxine (β = 0.74 ± 0.1649, p < 0.001), 56.8% with food (β = 0.45 ± 0.1550, p < 0.01), and 116.0% after intake of a ketogenic diet (β = 0.77 ± 0.3141, p < 0.05). All patients included were responders without evidence of an association between C0 and response status. In children with DEEs, systemic concentrations of CBD may be significantly increased when co-administered with levothyroxine, food, or a ketogenic diet.

Purpose: This retrospective study aimed to evaluate the efficacy and tolerability of sulthiame (STM) as an add-on treatment in 49 patients with non-self-limited focal epilepsies of childhood (non-SeLFE) resistant to other antiseizure medications (ASM) and/or non-pharmacological treatment., Methods: Patients with non-SeLFE who had failed to respond to at least five previous ASM, alone or in combination, were included in the study. All patients underwent neurological examination, brain magnetic resonance imaging repeated prolonged electroencephalography (EEG) or video-EEG studies, and neurometabolic studies. School achievements and/or performance on neuropsychological tests were also assessed. Sulthiame was added in doses ranging from 10 to 40 mg/kg/day. Efficacy was measured by comparing seizure frequency before and after initiating STM therapy., Results: Twenty-nine of 49 patients (59.1%) who received STM as add-on therapy had a greater than 50% decrease in seizures after a mean follow-up of 35 months. One patient (2%) became seizure-free. Fourteen patients (40%) had a 25-50% seizure reduction. The mean time of response was 5 months (range, 3.5 to 6 months). No differences were found either between patients with a response of more or less than 50% or between the response of the focal seizure types (motor or non-motor, with or without consciousness impairment)., Conclusion: In our study, STM was found to be effective and well-tolerated in children and adolescents with non-SeLFE. In the patients who responded, improvement in the EEG was seen., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The study was conducted to analyze the possible diagnostic value of the electroclinical semiology of the epileptic seizures., Methods: We evaluated the medical records of 17 females and 5 males with CDKL5 deficiency disorder (CDD) considering the long-term evolution, including the polygraphic video-EEG recordings., Results: We recognized three disease phases. We found that the seizure semiology was already recognizable in the first phase of the syndrome. In the short-term evolution, all patients had focal motor and 12/21 hypermotor seizures. Both epileptic spasms and myoclonic seizures were already present in more than half of the cases in the first 2 months after onset. In the second phase, the intermediate period, the polymorphic pattern was maintained, but in eight patients the electroclinical pattern of epileptic encephalopathy with hypsarrhythmia appeared. In the long-term period, the seizure polymorphism continued but myoclonic and epileptic spasms diminished. Tonic seizures appeared in the last 2 phases. Progressively, with the aggravation of seizures and paroxysmal EEG abnormalities impairment of the neurocognitive status was observed. Severe behavioral disturbances were seen in eight and autistic-like features in 14., Conclusion: CDD is a true developmental and epileptic encephalopathy with a specific etiology characterized by the early appearance of epileptic seizures that quickly become polymorphic and drug resistant in infants that are most often female and already have neurological impairment. Polygraphic video-EEG recordings are important to recognize ictal events of the association of hypermotor seizures, epileptic spasms in clusters, and massive myoclonic jerks, already present at onset., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The aim of the study was to determine whether an easy-to-read patient education card given at the preoperative visit can increase patient recall of the planned surgery., Methods: This was a randomized controlled trial. Patients scheduled to undergo pelvic reconstructive surgery were recruited during their preoperative visits. All participants received standard surgical counseling, whereas the intervention group also received a 4 × 6 inch card highlighting the anticipated procedure. The primary outcome was correct recall of the planned surgery as measured by a preoperative questionnaire. Secondary outcomes were correct recall of the surgery postoperatively and patient satisfaction with the information provided., Results: One hundred twenty-eight patients were enrolled with 64 participants in each arm. One hundred twenty-seven participants were analyzed because 1 patient was lost to follow-up. No difference was found between patient demographics, including types of surgical procedures performed. There was a statistically significant improvement in preoperative recall: 30 of 63 participants (47.6%) in the intervention group answered all questions correctly versus 18 of 64 patients (28.6%) patients in the standard counseling group (P = 0.021). There was no difference in the postoperative scores between the 2 groups: 48.3% (28 of 58) and 52.5% (32 of 61) of the participants answered all questions correctly in the intervention and standard counseling only groups, respectively (P = 0.648). There was no difference in satisfaction scores, with a median score of 20 out of 20 for either group (interquartile range = 19-20)., Conclusions: A concise and easy-to-use education card enhanced patient preoperative recall of the proposed surgery. This difference was not sustained postoperatively. High satisfaction with the information provided was reported regardless of counseling method., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2021 American Urogynecologic Society. All rights reserved.)

Introduction: Initiation of ketogenic diet therapies (KDT) for pediatric epilepsy is usually done on an inpatient basis and the diet is managed during clinical appointments following a protocol of visits and routine tests. Because of the 2019 coronavirus disease (COVID-19) pandemic and the associated lock-down measures, we switched from outpatient to telemedicine-based KDT initiation., Objective: To explore the feasibility, effectiveness, and safety of online KDT initiation and follow-up by comparing a group of children with drug-resistant epilepsy that was managed by telemedicine compared to a group that was treated on an outpatient basis., Materials and Methods: An observational study was conducted in two groups of patients with drug-resistant epilepsy who initiated KDT and were followed up with an online versus an outpatient modality by the interdisciplinary KDT team of Hospital Pediatria JP Garrahan in Buenos Aires, Argentina. Dietary compliance, ketosis, retention rate, adverse effects, number of contacts, and clinical outcome were evaluated at 1, 3, and 6 months on the diet., Results: Overall, 37 patients were included, of whom 18 started the KD by telemedicine and 19 on an outpatient basis. Minimum follow-up of the patients was 6 months. All patients received the classic ketogenic diet. No statistical differences between the two groups regarding efficacy and safety of the diet were found., Conclusions: Our results support the feasibility and safety of initiating and management of KDT by telemedicine. Patients and their families should be carefully selected in order to guarantee a good outcome., (Copyright © 2022. Published by Elsevier Ltd.)

Sialic acid (SA) is a monosaccharide usually linked to the terminus of glycan chains on the cell surface. It plays a crucial role in many biological processes, and hypersialylation is a common feature in cancer. Lectins are widely used to analyze the cell surface expression of SA. However, these protein molecules are usually expensive and easily denatured, which calls for the development of alternative glycan-specific receptors and cell imaging technologies. In this study, SA-imprinted fluorescent core-shell molecularly imprinted polymer particles (SA-MIPs) were employed to recognize SA on the cell surface of cancer cell lines. The SA-MIPs improved suspensibility and scattering properties compared with previously used core-shell SA-MIPs. Although SA-imprinting was performed using SA without preference for the α2,3- and α2,6-SA forms, we screened the cancer cell lines analyzed using the lectins Maackia Amurensis Lectin I (MAL I, α2,3-SA) and Sambucus Nigra Lectin (SNA, α2,6-SA). Our results show that the selected cancer cell lines in this study presented a varied binding behavior with the SA-MIPs. The binding pattern of the lectins was also demonstrated. Moreover, two different pentavalent SA conjugates were used to inhibit the binding of the SA-MIPs to breast, skin, and lung cancer cell lines, demonstrating the specificity of the SA-MIPs in both flow cytometry and confocal fluorescence microscopy. We concluded that the synthesized SA-MIPs might be a powerful future tool in the diagnostic analysis of various cancer cells.

Introduction: Noticing health warnings on cigarette packages has been associated with thinking about quitting. This study examined sociodemographic characteristics associated with awareness of health warnings on cigarette packages and thinking about quitting because of health warning labels among adults who currently smoked tobacco., Methods: We analyzed data from the 2017 Zambia WHO STEPS survey (STEPwise approach to surveillance) for noncommunicable disease risk factors. Descriptive analyses and logistic regression were performed to assess the association of select sociodemographic characteristics with awareness of health warnings and thinking about quitting because of health warnings., Results: Adults who currently smoked tobacco who were aged 30-44 years, of Chewa ethnicity, or with a formal education, were more likely to be aware of health warnings than those aged 18-29 years (adjusted prevalence ratio, APR=1.26; 95% CI: 1.02-1.54), of Bemba ethnicity (APR=1.43; 95% CI: 1.17-1.74), or with no formal education (APR: 2.61-5.95). Among all adults who currently smoked, those of Chewa ethnicity (APR=1.55; 95% CI: 1.03-2.35), or with a formal education (APR:1.80-4.38), were more likely to report thinking about quitting because of health warnings than those who were of Bemba ethnicity or with less than primary school education level. Women who currently smoked were 49% less likely (APR=0.51; 95% CI: 0.23-0.84) to report thinking about quitting than men. Among a subset of adults who currently smoked who were aware of health warning labels, no sociodemographic characteristics were significantly associated with thinking about quitting in unadjusted or adjusted models., Conclusions: Sociodemographic characteristics such as sex, ethnicity, and education level were significantly associated with awareness of cigarette health warnings. Among cigarette smokers aware of health warnings, no sociodemographic differences in thinking about quitting were found. Tobacco control campaigns may need to target people of ethnicities with the highest smoking prevalence in the country., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© Phiri M. M. et al.)

Objective: We report our findings regarding effectiveness, safety, and tolerability of cannabidiol (CBD)-enriched medical cannabis as add-on therapy in children with drug-resistant epileptic encephalopathies (DEEs) after a median follow-up of 20 months., Methods: A prospective cohort study was conducted to assess effectiveness, safety, and tolerability of CBD-enriched medical cannabis oil added to standard antiseizure medications in children with drug-resistant DEE seen at a single center., Results: Between October 2018 and March 2020, 59 patients were enrolled. Mean age at enrollment was 10.5 years (range, 2-17 years). Median treatment duration was 20 months (range, 12-32). Median age at first seizure was 8 months (range, 1 day - 10 years). At the end of follow-up, 78% of the children had a ≥ 50% decrease in seizure frequency and 47.5% had a > 75% decrease. Seven patients (11.9%) were seizure free. The number of seizures was reduced from a median of 305/month to 90/month, amounting to a mean reduction of 57% and a median reduction of 71% (p < 0.0001). Adverse effects were mostly mild or moderate. CBD was discontinued in 17 patients (28.8%) due to lack of response to treatment, increased seizure frequency, intolerance to the drug, or poor compliance., Conclusion: In children with drug-resistant DEEs, long-term treatment of CBD-enriched medical cannabis as an adjuvant therapy to antiseizure therapy was found to be safe, well tolerated, and effective. Sustained reductions in seizure frequency and improvement of aspects of daily living were observed compared to our preliminary findings., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Coxsackievirus A24 variant (CVA24v) is responsible for several outbreaks and two pandemics of the highly contagious eye infection acute hemorrhagic conjunctivitis (AHC). Currently, neither prevention (vaccines) nor treatments (antivirals) are available for combating this disease. CVA24v attaches to cells by binding Neu5Ac-containing glycans on the surface of cells which facilitates entry. Previously, we have demonstrated that pentavalent Neu5Ac conjugates attenuate CVA24v infection of human corneal epithelial (HCE) cells. In this study, we report on the structure-based design of three classes of divalent Neu5Ac conjugates, with varying spacer lengths, and their effect on CVA24v transduction in HCE cells. In relative terms, the most efficient class of divalent Neu5Ac conjugates are more efficient than the pentavalent Neu5Ac conjugates previously reported., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: We studied cases with long-lasting epileptic spasms (ES) considered as a spasm status analyzing type of epilepsy, epileptic syndrome, etiology, treatment, and outcome in 21 patients., Methods: We evaluated the charts of 21 patients seen between June 2006 and July 2017 who met the electroclinical diagnostic criteria of a spasm status. The spasm status was defined as continuous ES lasting 30 min or longer., Results: The type of ES was mixed in nine patients, flexion in seven, and extension in five. Epileptic spasms were asymmetric in three patients and unilateral in two. They occurred on awakening in all patients, while during sleep they decreased in all and disappeared in three cases. The duration of the spasm status ranged from 40 min to 15 days according to the seizure diaries of patients and video-EEG recordings. Two well-defined subgroups of patients were recognized; the first included patients with West syndrome (WS) and the second other types of severe non-West epilepsy syndromes. The spasm status responded well to oral vigabatrin (VGB) in four patients, oral topiramate (TPM) in three, oral corticosteroids in one, and cannabidiol in another patient. A good response was observed with benzodiazepines in six patients, with phenytoin (PH) in two, and with phenobarbital (PB) in one. Adrenocorticotropic hormone (ACTH) was effective in one patient and the ketogenic diet in two. Prognosis depends on the etiology., Conclusion: In this study we identified patients with WS and other types of severe non-West epilepsy syndromes who had a particular type of long-lasting ES that, in spite of its long duration does not strictly meet the criteria of the International League against Epilepsy (ILAE) classification of status epilepticus, may be considered a spasm status., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Hypertension and diabetes are highly prevalent conditions in Chilean adults., Aim: To describe the demographic and clinical profiles, risk factors and complications associated with arterial hypertension (AH) and diabetes mellitus (DM) in patients ascribed to a cardiovascular health program at a public primary health care center in Santiago., Material and Methods: Review of medical records of 583 patients aged 37 to 95 years (56% women). Gender, age, smoking habits, blood pressure, glycated hemoglobin levels, LDL cholesterol and triglycerides levels, nutritional status in the last control carried out, and associated cardiovascular complications were recorded., Results: Thirty four percent (201 participants) and 36% (210 participants) had a decompensated DM and AH, respectively. Dyslipidemia was the main associated cardiovascular risk factor. The prevalence of obesity was 43% (249 participants). Twenty percent had chronic kidney disease and 13% had diabetic retinopathy., Conclusions: These patients have a high frequency of obesity, dyslipidemia, and chronic kidney disease.

Introduction: Ketogenic diet therapy (KDT) is a metabolic treatment with proven effectiveness for the treatment of drug-resistant epilepsy in children. Although previously not used in infants under 2 years of age, recent studies have shown KDT to be highly effective and well tolerated in infants with epilepsy, especially those with epileptic encephalopathies. Here, we describe the effectiveness and tolerability of the diet in infants up to 2 years of age., Material and Methods: A prospective study was conducted in a cohort of infants younger than 2 years of age with drug-resistant epilepsy who received the classic ketogenic diet using a specific protocol at a single center in Argentina., Results: 56 infants with treatment-refractory epilepsy were evaluated. The etiology was genetic in 21.4%, structural in 28.6%, unknown in 44.7%, and metabolic in 5.4%. At 3 months, a > 50% decrease in seizure frequency was observed in 35 patients (62.4%), of whom 11 (19.6%) became seizure free. At 6 months, 34 patients (60.7%) had a decrease in seizure frequency of > 50%, of whom 10 (17.8%) were seizure free. At the one-year follow-up, 27 patients (48.2%) had a > 50% decrease in seizure frequency, of whom six (10.7%) were seizure free. At two years, 14 patients (25%) had a > 50% seizure control, of whom four (7.1%) were seizure free. The most common early adverse effects were hypoglycemia and vomiting, while after 1 month and beyond metabolic acidosis, vomiting, and constipation more commonly found. A trend towards a higher rate of acute adverse events in infants younger than 1 year was observed., Conclusions: CKD showed to be a useful option in infants with treatment-resistant epilepsy. Adverse effects were common, but not a reason to discontinue the diet. Further studies are necessary to evaluate in which epilepsy syndromes and etiologies KDT is most effective., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Here we present a series of patients with WS that were refractory to antiseizure medications and the ketogenic diet and who were treated with cannabidiol-enriched cannabis oil (CBD) as add-on therapy analyzing efficacy, safety, and tolerability., Material and Methods: Medical records of eight patients with WS treated with CBD at a ratio of cannabidiol:Δ-9-tetrahydrocannabinol (CBD:THC) of 25:1 seen between May 2020 and March 2021 were retrospectively analyzed. In all patients CBD was started as add-on therapy., Results: Eight patients (six female and two male) who received CBD for treatment-resistant WS were evaluated. Ages ranged from 16 to 22 months. The etiology was unknown in five and structural in three. Initial CBD dose was 2 mg/kg/day which was uptitrated to a median dose of 12 mg/kg/day (range, 2-25). Prior to CBD initiation, patients had a mean of 63 seizures per day (range, 31-79). After a follow-up of between 6 and 13 months, a 75-99% decrease in seizure frequency was observed in two patients, a 50-74% decrease in two, a less than 50% decrease in three, and no changes in seizure frequency were seen in the remaining patient. The index of EEG abnormalities improved between 20 and 80% in seven patients concurrently with the reduction in seizures. Adverse effects were mild and transient. Somnolence was observed in one patient, nausea and vomiting in one, and behavior disturbances and irritability in another patient., Conclusion: This study evaluating the use of cannabidiol-enriched cannabis oil in children with WS showed that four (50%) of eight had a more than 50% seizure reduction with good tolerability., (Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Coxsackievirus A24 variant (CVA24v) is the primary causative agent of the highly contagious eye infection designated acute hemorrhagic conjunctivitis (AHC). It is solely responsible for two pandemics and several recurring outbreaks of the disease over the last decades, thus affecting millions of individuals throughout the world. To date, no antiviral agents or vaccines are available for combating this disease, and treatment is mainly supportive. CVA24v utilizes Neu5Ac-containing glycans as attachment receptors facilitating entry into host cells. We have previously reported that pentavalent Neu5Ac conjugates based on a glucose-scaffold inhibit CVA24v infection of human corneal epithelial cells. In this study, we report on the design and synthesis of scaffold-replaced pentavalent Neu5Ac conjugates and their effect on CVA24v cell transduction and the use of cryogenic electron microscopy (cryo-EM) to study the binding of these multivalent conjugates to CVA24v. The results presented here provide insights into the development of Neu5Ac-based inhibitors of CVA24v and, most significantly, the first application of cryo-EM to study the binding of a multivalent ligand to a lectin.

Vitamin B12 is a water-soluble vitamin that plays a fundamental role as an essential cofactor for two enzymes responsible for the production of succinyl-CoA and methionine. Vitamin B12 deficiency can occur in infants and may be related to the breastfeeding mother's adherence to a vegan diet or somatic diseases in the mother. It should be differentiated from inborn errors of vitamin B12 metabolism. Herein, we report the cases of three infants with West syndrome; all three were breastfed by mothers who followed a strict vegan diet. In one of the three infants, West syndrome developed during treatment with vitamin B12 and normalization of the vitamin B12 level. Early treatment and replacement therapy are worthwhile to prevent serious neurological problems and to improve the patient's clinical course., Competing Interests: None., (Thieme. All rights reserved.)

Objective: We analyzed the records of 198 patients with West syndrome (WS) seen at a single pediatric neurology center in Argentina between June 2004 and June 2017. Five patients with infection-related spontaneous remission of the electroclinical manifestations were identified., Methods: The following parameters were investigated: personal and family history, clinical characteristics of the seizures - mainly spasms - and EEG findings, type of treatment, and outcome. The inclusion criteria for WS were epileptic spasms (ES) in clusters, hypsarrhythmia, and mental deterioration. Infants with ES without hypsarrhythmia and other epileptic encephalopathies with ES were excluded., Results: Five children, four boys and one girl, met the inclusion criteria of WS with spontaneous remission after a viral infection. The etiology of ES was unknown in four patients and one had a structural etiology. All patients had spontaneous remission of the ES and normalization of the EEG following acute upper respiratory infection in four and exanthema subitum in one; all of them had fever between 38.5 and 40 °C., Conclusion: We report five patients with spontaneous remission of WS following acute viral infection, associated with a respiratory virus in four and exanthema subitum in one., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The synthesis of 4- O -alkyl analogues of N -acetylneuraminic acid (Neu5Ac) and the scope of the reaction are described. Activated alkyl halides and sulfonates and primary alkyl iodides give products in useful yields. The utility of the methodology is exemplified using a thiophenyl Neu5Ac building block to synthesize a 4- O -alkyl DANA analogue. These results expand the toolbox of Neu5Ac chemistry with value in drug discovery and for the design of novel tools to study the biology of Neu5Ac lectins.

Objective: We describe the electroclinical characteristics of a series of 26 patients with idiopathic West syndrome (WS), who had an excellent response to treatment with vigabatrin (VGB) and corticosteroids alone or in combination., Methods: Evaluating the records of 178 patients with WS studied at Garrahan Hospital, Niño Jesús Hospital, and Clínica San Lucas between January 2005 and June 2017, we selected 26 patients that met the inclusion criteria of idiopathic WS. The inclusion criteria for idiopathic WS were (1) no personal history of disease, (2) normal neurological examination and neurodevelopment, (3) symmetric spasms in clusters not preceded by any other type of seizure, (d) symmetric hypsarrhythmia, (e) normal electroencephalogram (EEG) background, e.g., normal sleep EEG pattern, (f) normal magnetic resonance imaging (MRI) recording, (g) normal neurometabolic and genetic studies, and (h) at least 2 years of follow-up., Results: Fifteen boys and 11 girls met the inclusion criteria of idiopathic WS. The current age of the children ranges between 2 years 10 months and 12 years 10 months. Age at first epileptic spasms (ES) ranged from 4 to 11 months, with a mean age of 7 and a median of 7.5 months, respectively; ES were in clusters, bilateral and symmetrical in all cases. Spasms were flexor in nine (34.7%), mixed flexor-extensor in 15 (57.7%), and extensor in three (7.6%). In all patients the EEG showed typical pattern of hypsarrhythmia., Conclusion: These patients with idiopathic WS who have an excellent response to initial treatment should be treated for a short period of time with adrenocorticotropic hormone (ACTH) and VGB alone or in combination., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Growing interest in the clinical use of cannabidiol (CBD) as adjuvant therapy for pediatric refractory epileptic encephalopathy emphasizes the need for drug treatment optimization. The aim of this study was to characterize the pharmacokinetics of CBD in pediatric patients with refractory epileptic encephalopathy receiving an oil-based oral solution. To evaluate CBD concentrations, six serial blood samples per patient were collected after the morning dose of CBD, at least 21 days after the beginning of treatment. Twelve patients who received a median (range) dose of 12.2 (5.3-19.4) mg/kg/d (twice daily) were included in the analysis. Median (range) CBD time to maximum plasma concentration, maximum plasma concentration, and area under the concentration versus time curve up to 6 hours after dosing were 3.2 hours (1.9-6.2), 49.6 ng/mL (14.4-302.0), and 226.3 ng ⋅ h/mL (70.5-861.3), respectively. CBD systemic exposure parameters were in the lower range of previous reports in pediatric patients receiving doses in a similar range. Most of our patients (83%) showed little CBD plasma level fluctuation during a dosing interval, comparable to that encountered after oral administration of an extended release drug delivery system. CDB administration was generally safe and well tolerated, and a novel levothyroxine-CBD interaction was recorded. Similar to other studies, large interindividual variability in CBD exposure was observed, encouraging the use of CBD therapeutic drug monitoring., (© 2020 International League Against Epilepsy.)

Aim: The aim of this study was to analyze electroclinical features of a group of patients with West syndrome (WS) who subsequently developed Lennox-Gastaut syndrome (LGS) during the transition between both syndromes., Methods: A retrospective and descriptive study was conducted of a series of patients diagnosed with WS who developed LGS seen at Hospital de Pediatría Prof. Dr. JP Garrahan between January 2012 and January 2019. The medical charts of 170 patients with WS were analyzed. In 63 (37 %) of the children WS evolved to LGS., Results: During the transition from WS to LGS four well-defined electroclinical patterns were recognized. The first corresponded to a group of patients with multiple seizure types, including epileptic spasms associated with multifocal paroxysms; the electroclinical pattern in second group showed mainly focal seizures associated with focal discharges in the EEG; the third group showed predominance of epileptic spasms and myoclonic seizures associated with diffuse spike-and-wave and polyspike-and-wave paroxysms; and the remaining group was characterized by a mixed electroclinical pattern including features of the other three groups. All patients had a neuropsychological deficit. Worsening of cognition and behavior was observed during the transition period in 11, 8, and 5 patients of groups 1, 3, and 4, respectively., Conclusion: Our study of the transition period from WS to LGS allowed us to recognize four well-defined electroclinical patterns. The early recognition of the different patterns could, in the future, support a more precocious prognostic evaluation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to assess parent satisfaction with the management of ketogenic diet therapies (KDTs) through telemedicine using WhatsApp as the main tool., Methods: Parent satisfaction was longitudinally evaluated through questionnaires. The survey was developed with Google Questionnaire forms and sent via WhatsApp. The questionnaire consisted of 13 items concerning the management of KDTs using telemedicine in the context of the coronavirus disease 2019 (COVID-19) pandemic. Our population of patients has limited financial resources and low levels of education. Given that many families did not have either computers or WIFI, or any other access to information or communication technology, WhatsApp was chosen as a tool as it was available on the cell phones of all families and the professionals., Results: Our survey showed that 96.3% of the parents were satisfied with the management of KDTs through telemedicine. The main benefits observed were the possibility of continuing treatment during the COVID-19 pandemic and the ease of accessing the professional team from the comfort of their home. Overall, 72.2% of the families would recommend using telemedicine for KDTs in any situation regardless of the pandemic. None of the families reported that they would recommend against treatment by telemedicine. The availability of a social support network (parents WhatsApp group) coordinated by professionals from the KDT team was considered to be useful by most respondents (90%)., Conclusions: Our study suggests that management of children with DRE on KDTs through telemedicine is feasible, well accepted by the families, and probably as safe as conventional medicine. WhatsApp may be an interesting telemedicine tool to start and maintain KDTs., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Coxsackievirus A24 variant (CVA24v) and human adenovirus 37 (HAdV-37) are leading causative agents of the severe and highly contagious ocular infections acute hemorrhagic conjunctivitis and epidemic keratoconjunctivitis, respectively. Currently, neither vaccines nor antiviral agents are available for treating these diseases, which affect millions of individuals worldwide. CVA24v and HAdV-37 utilize sialic acid as attachment receptors facilitating entry into host cells. Previously, we and others have shown that derivatives based on sialic acid are effective in preventing HAdV-37 binding and infection of cells. Here, we designed and synthesized novel pentavalent sialic acid conjugates and studied their inhibitory effect against CVA24v and HAdV-37 binding and infection of human corneal epithelial cells. The pentavalent conjugates are the first reported inhibitors of CVA24v infection and proved efficient in blocking HAdV-37 binding. Taken together, the pentavalent conjugates presented here form a basis for the development of general inhibitors of these highly contagious ocular pathogens.

Objective: The aim of this study was to perform a molecular characterization of 17 Argentinean pediatric patients with diagnosis of having epileptic encephalopathies (EEs) of the first year of life without known etiology, applying next-generation sequencing (NGS)., Methods: We included 17 patients with EE with age of onset under 12 months without known etiology after ruling out structural abnormalities, metabolic disorders, and large chromosomal abnormalities. They presented with the following clinical phenotypes: Dravet syndrome (DS; n: 7), epilepsy of infancy with migrating focal seizures (EIMFS; n: 3), West syndrome (WS; n: 2), and undetermined epileptic encephalopathy (UEE; n: 5). Neurologic examinations, seizure semiology, brain magnetic resonance imaging, and standard electroencephalography (EEG) or video-EEG studies were performed in all cases. Using a custom amplicon strategy, we designed an NGS panel to study 47 genes associated with EEs., Results: Pathogenic variants were detected in 8 cases (47%), including seven novel pathogenic variants and one previously reported as being pathogenic. The pathogenic variants were identified in 6 patients with DS (SCN1A gene), one with EIMFS (SCN2A gene), and one with UEE (SLC2A1 gene). Nonrelevant variants were identified in the patients with WS., Conclusion: We demonstrated the feasibility of an NGS-gene panel approach for the analysis of patients with EE in our setting. A genetic diagnosis was achieved in nearly 50% of patients, 87% of them presenting with nonpreviously reported variants. The early identification of the underlying causative genetic alteration will be a valuable tool for providing prognostic information and genetic counselling and also to improve therapeutic decisions in Argentinean patients., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to assess parent satisfaction three years after the implementation of a pediatric epilepsy telemedicine program., Methods: The program was developed with support from the Ministry of Health through Hospital Nacional de Pediatría J.P. Garrahan. A secure internet connection was used for high-speed, high-definition video and audio. Synchronous face-to-face consultation between the patient and the neurologist was used. To evaluate the success of the program, at the end of the consultation the parent or caregiver of the patient was asked to complete a survey evaluating satisfaction with health care, cost, and privacy issues. The survey was administered by community health workers to the parents of patients that were in follow-up or first seen at the rural health posts during 2019., Results: Between January and December 2019, 116 consecutive parents of patients seen at the epilepsy telemedicine clinic filled out a semistructured questionnaire. Mean age of the patients was 8.5 years (range, 1-17 years); 85 % of the patients had a follow-up of more than 6 months. All the families felt supported by the team and were satisfied with the program in terms of epilepsy management. Less work- and schooltime lost, less travel time and costs, better access to medication, and more regular follow-up visits were reported. The parents considered they had received clear information about the epilepsy of their child., Conclusion: Telemedicine proves to be an important tool in the comprehensive management of people with epilepsy., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: We report our preliminary findings regarding effectiveness, safety, and tolerability of cannabidiol (CBD) added to antiepileptic therapy in a cohort of children with drug-resistant epileptic encephalopathies (EEs) with a mean follow-up of 8.5 months (range, 3-12 months)., Methods: A prospective cohort study was designed with the aim of assessing the effectiveness, safety, and tolerability of the addition of CBD to standard antiseizure medications (ASMs) in children with drug-resistant EE enrolled at a single center (Neurology Department, Hospital de Pediatría "Juan P. Garrahan", Buenos Aires, Argentina)., Results: Fifty patients were enrolled between October 2018 and October 2019, 49 of whom had a follow-up of at least 3 months at the time this interim analysis was performed. Mean age at enrollment was 10.5 years (range 2-16). Median age at first seizure was 7 months. Up to the last visit of each patient (follow-up 3-12 months) 39/49 children (80 %) had responded to treatment with a decrease in seizure frequency. Overall, 77.6 % of the patients had a seizure reduction of at least 25 %, 73.5 % had a ≥ 50 % reduction, and 49 % had a ≥ 75 % reduction. Mean monthly seizure frequency was reduced from 959 to 381 (median decrease from 299 to 102, range, 38-1900; median decrease 66 %, p < 0.001). All adverse effects were mild or moderate. The most common adverse effect was drowsiness (in 32 %), usually reversed by adjusting clobazam dose (in 12 children)., Conclusion: In children with drug-resistant EEs, CBD oil as an adjuvant therapy to antiepileptic therapy seems safe, well tolerated, and effective., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Despite the rapid increase of clinical and basic-science knowledge on ketogenic diet therapies over the past years, it has not always been easy to determine the adequate indications of this treatment. Over the nearly 100 years of use, from being a last resource in the therapeutic algorithm, the diet has become one of the four main treatments for patients with difficult-to-control epilepsy together with antiepileptic drugs, surgery, and vagus nerve stimulation. The use of the diet has also changed. The current paper will briefly discuss the history of the diet together with a review of the literature regarding its most important indications and how they have evolved. The concept of the importance of defining the type of seizure, type of syndrome, and etiology in the selection of patients and timing of diet initiation has been gaining importance. This paper explores how the indications of the diet changed together with the shifting focus of epilepsy teams towards its use in different types of epilepsy and epilepsy syndromes and according to etiologies and as an alternative option in refractory and superrefractory status epilepticus., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To provide information on the effect of the coronavirus disease of 2019 (COVID-19) pandemic on people with epilepsy and provide consensus recommendations on how to provide the best possible care for people with epilepsy while avoiding visits to urgent care facilities and hospitalizations during the novel coronavirus pandemic., Methods: The authors developed consensus statements in 2 sections. The first was "How should we/clinicians modify our clinical care pathway for people with epilepsy during the COVID-19 pandemic?" The second was "What general advice should we give to people with epilepsy during this crisis? The authors individually scored statements on a scale of -10 (strongly disagree) to +10 (strongly agree). Five of 11 recommendations for physicians and 3/5 recommendations for individuals/families were rated by all the authors as 7 or above (strongly agree) on the first round of rating. Subsequently, a teleconference was held where statements for which there was a lack of strong consensus were revised., Results: After revision, all consensus recommendations received a score of 7 or above. The recommendations focus on administration of as much care as possible at home to keep people with epilepsy out of health care facilities, where they are likely to encounter COVID-19 (including strategies for rescue therapy), as well as minimization of risk of seizure exacerbation through adherence, and through ensuring a regular supply of medication. We also provide helpful links to additional helpful information for people with epilepsy and health providers., Conclusion: These recommendations may help health care professionals provide optimal care to people with epilepsy during the coronavirus pandemic., (© 2020 American Academy of Neurology.)

Multiple studies have shown that psychological distress in epithelial ovarian cancer (EOC) patients is associated with worse quality of life and poor treatment adherence. This may influence chemotherapy response and prognosis. Moreover, although stress hormones can reduce cisplatin efficacy in EOC treatment, their effect on the integrity of DNA remains poorly understood. In this study, we investigated whether norepinephrine and epinephrine can induce DNA damage and modulate cisplatin-induced DNA damage in three EOC cell lines. Our data show that norepinephrine and epinephrine exposure led to increased nuclear γ-H2AX foci formation in EOC cells, a marker of double-strand DNA breaks. We further characterized norepinephrine-induced DNA damage by subjecting EOC cells to alkaline and neutral comet assays. Norepinephrine exposure caused DNA double-strand breaks, but not single-strand breaks. Interestingly, pre-treatment with propranolol abrogated norepinephrine-induced DNA damage indicating that its effects may be mediated by β-adrenergic receptors. Lastly, we determined the effects of norepinephrine on cisplatin-induced DNA damage. Our data suggest that norepinephrine reduced cisplatin-induced DNA damage in EOC cells and that this effect may be mediated independently of β-adrenergic receptors. Taken together, these results suggest that stress hormones can affect DNA integrity and modulate cisplatin resistance in EOC cells.

Introduction: Hispanic adults make up a growing share of US adult smokers, and smoking is a major preventable cause of disease and death among Hispanic adults. No previous study has compared trends in smoking cessation behaviors among Hispanic adults and non-Hispanic white adults over time. We examined trends in cessation behaviors among Hispanic and non-Hispanic white adult cigarette smokers during 2000-2015., Methods: Using self-reported data from the National Health Interview Survey, we compared trends in quit attempts, receipt of advice to quit from a health professional, and use of cessation treatment (counseling and/or medication) among Hispanic and non-Hispanic white adult smokers. We also assessed these behaviors among 4 Hispanic subgroups. We conducted analyses in 2018-2019., Results: Past-year quit attempts increased during 2000-2015 among both non-Hispanic white and Hispanic smokers, with no significant differences between these groups. Receiving advice to quit increased significantly among non-Hispanic white adults but did not increase significantly among Hispanic adults. Cessation treatment use increased among both non-Hispanic white and Hispanic adults. Throughout 2000-2015, the prevalence of receiving advice to quit and using cessation treatments was lower among Hispanic adults than non-Hispanic white adults. In 2015, a higher proportion of Hispanic than non-Hispanic white smokers visited a health care provider without receiving advice to quit., Conclusion: Hispanic adult smokers are less likely to receive advice to quit and to use proven cessation treatments than non-Hispanic white smokers, and this pattern persisted over time. Culturally competent educational initiatives directed at both providers and Hispanic communities could help eliminate this marked and persistent disparity.

Mounting preclinical and clinical evidence continues to support a role for the neuroendocrine system in the modulation of tumor biology and progression. Several studies have shown data supporting a link between chronic stress and cancer progression. Dysregulation of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in promoting angiogenesis, tumor cell proliferation and survival, alteration of the immune response and exacerbating inflammatory networks in the tumor microenvironment. Here, we review how SNS and HPA dysregulation contributes to disturbances in immune cell populations, modifies cancer biology, and impacts immunotherapy response. We also highlight several interventions aimed at circumventing the adverse effects stress has on cancer patients., (Copyright © 2019 Colon-Echevarria, Lamboy-Caraballo, Aquino-Acevedo and Armaiz-Pena.)

Purpose: The aim of this study was to analyze patients whose only manifestation of epilepsy were generalized tonic-clonic seizures (GTCS) during childhood and discuss its validity as separate syndrome of childhood., Methods: We included children with at least two unprovoked GTCS between 3 and 11 years of age, no other seizure types at diagnosis, normal psychomotor development and neurological examination, an EEG with normal background and paroxysms of generalized spikes and waves with a frequency 2.5 Hz or above, and an unknown cause for epilepsy. Only patients with a follow-up >2 years were included., Results: Over a 12-year period (2005-2017) 26 patients met the inclusion criteria of epilepsy with GTCS only. Mean age at onset was 5 years. The seizures occurred while awake in 16 patients, on awakening in two, and during sleep in eight patients. The duration of seizures was around 3 min. Generalized spike-and-wave discharges were observed in all patients when awake and during sleep in eight and 26 patients, respectively. Nineteen responded well to valproic acid or levetiracetam. Two patients who received clobazam initially did not respond well; however, a switch to valproic acid resulted in excellent seizure control. Antiepileptic treatment was discontinued in sixteen patients who remained seizure free over a period of 2-9 years of follow-up., Conclusion: Epilepsy with GTCS alone in childhood is a type of epilepsy; however, it may be considered as a well-defined epileptic syndrome. Patients responded well to valproic acid or levetiracetam., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Encephalopathy with continuous spike-waves during slow-wave sleep (CSWS) evolves over time, and three stages can be recognized: before the onset of CSWS, during CSWS, and after the CSWS period. Clinical seizures tend to remit spontaneously around puberty. This pattern is independent of the etiological lesion. The CSWS also disappears in all cases. Focal abnormalities instead, may persist for some time after the disappearance of CSWS. The disappearance of the clinical seizures and CSWS may be simultaneous or seizures may disappear before or after disappearance of the CSWS pattern on the EEG. Electroclinical parameters in the pre-CSWS period that have been proposed to predict a poor outcome are early-onset seizures, appearance of new seizures, and a significant increase in seizure frequency. From the electrical point of view, an increase in the frequency of the interictal EEG paroxysms while awake and during sleep and bilateral spike-and-wave paroxysms may also be predictive of a poor evolution in CSWS. When CSWS disappears, neurocognitive and behavioral status improve, but in most patients, residual moderate to severe neurocognitive impairments remain. In non-lesional epilepsy, cognitive recovery after cessation of the CSWS depends on the severity and duration of the initial regression. The duration of the CSWS seems to be the most important predictor of cognitive outcome. Early recognition and effective therapy to reduce the seizures and resolve the CSWS may be crucial to improve long-term prognosis. Cognitive recovery is observed in patients who respond well to AED treatment and outcome depends on the etiology.

Five pediatric and adult neurologists with clinical and research interests in Encephalopathy related to Status Epilepticus during slow Sleep (ESES) express their opinions on definition, diagnostic assessment and terminology that may be considered for this condition. The aim of this "debate" is to identify aspects in which there is a shared opinion and areas where there are still controversies in the classification and suggest areas which demand further studies and research.

Human adenoviruses (HAdV) are the most common cause of ocular infections. Species B human adenovirus type 3 (HAdV-B3) causes pharyngoconjunctival fever (PCF), whereas HAdV-D8, -D37, and -D64 cause epidemic keratoconjunctivitis (EKC). Recently, HAdV-D53, -D54, and -D56 emerged as new EKC-causing agents. HAdV-E4 is associated with both PCF and EKC. We have previously demonstrated that HAdV-D37 uses sialic acid (SA)-containing glycans as cellular receptors on human corneal epithelial (HCE) cells, and the virus interaction with SA is mediated by the knob domain of the viral fiber protein. Here, by means of cell-based assays and using neuraminidase (a SA-cleaving enzyme), we investigated whether ocular HAdVs other than HAdV-D37 also use SA-containing glycans as receptors on HCE cells. We found that HAdV-E4 and -D56 infect HCE cells independent of SAs, whereas HAdV-D53 and -D64 use SAs as cellular receptors. HAdV-D8 and -D54 fiber knobs also bound to cell-surface SAs. Surprisingly, HCE cells were found resistant to HAdV-B3 infection. We also demonstrated that the SA-based molecule i.e., ME0462, designed to bind to SA-binding sites on the HAdV-D37 fiber knob, efficiently prevents binding and infection of several EKC-causing HAdVs. Surface plasmon resonance analysis confirmed a direct interaction between ME0462 and fiber knobs. Altogether, we demonstrate that SA-containing glycans serve as receptors for multiple EKC-causing HAdVs, and, that SA-based compound function as a broad-spectrum antiviral against known and emerging EKC-causing HAdVs.