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Objective: Epilepsy is recognized increasingly as a network disease, with changes extending beyond the epileptogenic zone (EZ). However, more studies of structural connectivity are needed to better understand the behavior and nature of this condition., Methods: In this study, we applied differential tractography, a novel technique that measures changes in anisotropic diffusion, to assess widespread structural connectivity alterations in a total of 42 patients diagnosed with medically refractory epilepsy (MRE), including 27 patients with focal epilepsy and 15 patients with multifocal epilepsy that were included to validate our hypothesis. All patients were compared individually to an averaged database constructed from 19 normal controls regressed by age and sex., Results: Statistical analyses revealed specific distribution patterns of tracts with increased connectivity that were located in multiple subcortical structures across all patients including the arcuate fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, uncinate fasciculus, fornix, and short U fibers. Conversely, pathways with a significant decrease in connectivity (p < .05) exhibited a more central distribution near mesial structures across all patients (corpus callosum, cingulum, corticospinal tract, and sensory fibers)., Significance: Our findings add to the growing evidence that focal epilepsy is not solely anatomically confined, but is rather a network disorder that extends beyond the EZ, and differential tractography shows strong potential as a clinical biomarker for assessing structural connectivity alterations in patients with epilepsy., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: The COVID-19 pandemic has had major and potentially long-lasting effects on mental health and wellbeing across populations worldwide. However, these impacts were not felt equally, leading to an exacerbation of health inequalities, especially affecting vulnerable populations such as migrants, refugees and asylum seekers. Aiming to inform the adaptation and implementation of psychological intervention programmes, the present study investigated priority mental health needs in this population group., Methods: Participants were adult asylum seekers, refugees and migrants (ARMs) and stakeholders with experience in the field of migration living in Verona, Italy, and fluent in Italian and English. A two-stage process was carried out to examine their needs using qualitative methods including free listing interviews and focus group discussions, according to Module One of the DIME (Design, Implementation, Monitoring, and Evaluation) manual. Data were analyzed using an inductive thematic analyses approach., Results: A total of 19 participants (12 stakeholders, 7 ARMs) completed the free listing interviews and 20 participants (12 stakeholders and 8 ARMs) attended focus group discussions. Salient problems and functions that emerged during free listing interviews were discussed during the focus group discussions. During the COVID-19 pandemic, ARMs struggled with many everyday living difficulties in their resettlement country due to social and economic issues, revealing a strong influence of contextual factors in determining mental health. Both ARMs and stakeholders highlighted a mismatch between needs, expectations and interventions as factors that may hamper proper implementation of health and social programmes., Conclusions: The present findings could help in the adaptation and implementation of psychological interventions targeting the needs of asylum seekers, refugees and migrants aiming to find a match between needs, expectations, and the corresponding interventions., Trial Registration: Registration number 2021-UNVRCLE-0106707, February 11 2021., (© 2023. The Author(s).)

Persistence of the human immunodeficiency virus type-1 (HIV-1) latent reservoir in infected individuals remains a problem despite fully suppressive antiretroviral therapy (ART). While reservoir formation begins during acute infection, the mechanisms responsible for its establishment remain unclear. CD8 + T cells are important during the initial control of viral replication. Here we examined the effect of CD8 + T cells on formation of the latent reservoir in simian immunodeficiency virus (SIV)-infected macaques by performing experimental CD8 + depletion either before infection or before early (that is, day 14 post-infection) ART initiation. We found that CD8 + depletion resulted in slower decline of viremia, indicating that CD8 + lymphocytes reduce the average lifespan of productively infected cells during acute infection and early ART, presumably through SIV-specific cytotoxic T lymphocyte (CTL) activity. However, CD8 + depletion did not change the frequency of infected CD4 + T cells in the blood or lymph node as measured by the total cell-associated viral DNA or intact provirus DNA assay. In addition, the size of the persistent reservoir remained the same when measuring the kinetics of virus rebound after ART interruption. These data indicate that during early SIV infection, the viral reservoir that persists under ART is established largely independent of CTL control., (© 2023. The Author(s).)

Diabetes mellitus (DM) is a very prevalent chronic disease. Among the treatments for DM, insulin is the most potent antidiabetic agent. However a significant proportion of patients fail to achieve Errors in the application of insulin are an important and correctable factor in many cases. We present the case of a patient with DM who, due to poor insulin application technique and hygiene, develops a skin and soft tissue infection with subsequent appearance of Fusarium oxysporum. It is important to emphasize the relevance of diabetes education in insulinized patients and the role of diabetes educators in their care. On the other hand, it is important to emphasize the importance of taking cultures by soft tissue puncture in case of local signs of infection.

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, psychiatric, and cognitive symptoms. Due to its diverse manifestations, the scientific community has long recognized the need for sensitive, objective, individualized, and dynamic disease assessment tools. We examined the feasibility of Differential Tractography as a biomarker to evaluate correlation of symptom severity and of HD progression at the individual level. Differential tractography is a novel tractography modality that maps pathways with axonal injury characterized by a decrease of anisotropic diffusion pattern. We recruited sixteen patients scanned at 0-, 6-, and 12-month intervals by diffusion MRI scans for differential tractography assessment and correlated its volumetric findings with the Unified Huntington's Disease Rating Scale (UHDRS). Deterministic fiber tracking algorithm was applied. Longitudinal data was modeled using the generalized estimating equation (GEE) model and correlated with UHDRS scores, in addition to Spearman correlation for cross-sectional data. Our results show that volumes of affected pathways revealed by differential tractography significantly correlated with UHDRS scores in longitudinal data (p-value < 0.001), and chronological changes in differential tractography also correlated with the changes in UHDRS (p-value < 0.001). This technique opens new clinical avenues as a clinical translational tool to evaluate presymptomatic and symptomatic gene positive individuals. Our results provide support that differential tractography has the potential to be used as a dynamic imaging biomarker to assess at the individual level in a non-invasive manner, disease progression in HD. Critically important, differential tractography proves to be a quantitative tool for following degeneration in presymptomatic patients, with potential applications in clinical trials., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The Woven EndoBridge has proved to be a safe and effective treatment, especially for wide-neck intracranial aneurysms. The recent fifth-generation Woven EndoBridge came with smaller devices. The purpose of this study was to assess the safety and efficiency of Woven EndoBridge treatment of small and very small aneurysms., Materials and Methods: Between September 2017 and March 2020, all consecutive patients treated with a 3- or 3.5 mm-width Woven EndoBridge device were included in this retrospective intention-to-treat study. Clinical and radiologic findings were evaluated at immediate and last-available follow-up. Angiographic outcome was assessed by an external expert reader., Results: One hundred twenty-eight aneurysms were treated with a fifth-generation Woven EndoBridge device including 29 with a width of ≤3.5 mm. Ten aneurysms were ruptured (34%). In 3 cases (10%), Woven EndoBridge treatment could not be performed because the aneurysm was still too small for the smallest available Woven EndoBridge device and another endovascular strategy was chosen. The median follow-up time was 11.2 months. Complete and adequate occlusion was obtained in 71% and 90% of the treated aneurysms, respectively. Retreatment was needed in 2 cases (10%). Symptomatic ischemic complications leading to transient neurologic deficits occurred in 2 cases (7%) (1 procedure-related and 1 device-related) but with full spontaneous recovery at discharge., Conclusions: The fifth-generation Woven EndoBridge device seems to be a safe and technically feasible treatment for both ruptured and unruptured small and very small intracranial aneurysms, with satisfactory occlusion rates on midterm follow-up. However, further study is needed to evaluate longer-term efficiency., (© 2021 by American Journal of Neuroradiology.)

We aimed to assess the effectiveness of an educational and hand hygiene program in daycare centers (DCCs) and homes on acute gastroenteritis (AGE) incidence in children attending DCCs., Methods: A randomized, controlled, and open study of 911 children aged 0-3 years attending 24 DCCs in Almería (Spain) with an 8-month follow-up was employed. Two intervention groups of DCCs families performed educational and hand hygiene measures, 1 with soap and water (soap and water group; n = 274), another with hand sanitizer (hand sanitizer group [HSG]; n = 339), and the control group (CG; n = 298) followed usual handwashing procedures. We compared AGE episode rates with Poisson regression model., Results: seven hundred fourteen AGE episodes were registered, significant differences between HSG and CG children were found during December and January. A multivariate model was applied and the adjusted incidence rate ratios by rotavirus vaccination found significant differences when children were previously vaccinated, the children in the soap and water group had a higher risk of AGE episodes (incidence rate ratio: 1.28, 95% confidence interval:1.0-1.64), compared with those in the HSG., Conclusions: This study demonstrated that hand hygiene programs that included hand sanitizer were most effective in the winter months. Further, the largest reduction of AGE episodes occurred in the children that followed hand hygiene programs including hand sanitizer and educational measures for DCC staff, parents, and children, and were vaccinated for rotavirus., (Copyright © 2020 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Context: Essential oils are prevalent in many medicinal plants used for oral hygiene and treatment of diseases., Objective: Medicinal plant species were extracted to determine the essential oil content. Those producing sufficient oil were screened for activity against Staphylococcus aureus, Escherichia coli, Streptococcus mutans, Lactobacillus acidophilus, and Candida albicans., Materials and Methods: Plant samples were collected, frozen, and essential oils were extracted by steam distillation. Minimum inhibitory concentrations (MIC) were determined using a tube dilution assay for those species yielding sufficient oil., Results: Fifty-nine of the 141 plant species produced sufficient oil for collection and 12 species not previously reported to produce essential oils were identified. Essential oil extracts from 32 species exhibited activity against one or more microbes. Oils from eight species were highly inhibitory to S. mutans, four species were highly inhibitory to C. albicans, and 19 species yielded MIC values less than the reference drugs., Discussion: RESULTS suggest that 11 species were highly inhibitory to the microbes tested and merit further investigation. Oils from Cinnamomum zeylanicum Blume (Lauraceae), Citrus aurantiifolia (Christm.) Swingle (Rutaceae), Lippia graveolens Kunth (Verbenaceae), and Origanum vulgare L. (Lamiaceae) yielded highly significant or moderate activity against all microbes and have potential as antimicrobial agents., Conclusion: Teas prepared by decoction or infusion are known methods for extracting essential oils. Oils from 11 species were highly active against the microbes tested and merit investigation as to their potential for addressing health-related issues and in oral hygiene.

NFIL3 is a transcription factor that regulates multiple immunologic functions. In myeloid cells, NFIL3 is IL-10 inducible and has a key role as a repressor of IL-12p40 transcription. NFIL3 is a susceptibility gene for the human inflammatory bowel diseases. In this article, we describe spontaneous colitis in Nfil3(-/-) mice. Mice lacking both Nfil3 and Il10 had severe early-onset colitis, suggesting that NFIL3 and IL-10 independently regulate mucosal homeostasis. Lymphocytes were necessary for colitis, because Nfil3/Rag1 double-knockout mice were protected from disease. However, Nfil3/Rag1 double-knockout mice adoptively transferred with wild-type CD4(+) T cells developed severe colitis compared with Rag1(-/-) recipients, suggesting that colitis was linked to defects in innate immune cells. Colitis was abrogated in Nfil3/Il12b double-deficient mice, identifying Il12b dysregulation as a central pathogenic event. Finally, germ-free Nfil3(-/-) mice do not develop colonic inflammation. Thus, NFIL3 is a microbiota-dependent, IL-10-independent regulator of mucosal homeostasis via IL-12p40.

Significant advances in our understanding of the in vivo functions of human cells and tissues and the human immune system have resulted from the development of 'humanized' mouse strains that are based on severely immunodeficient mice with mutations in the interleukin-2 receptor common γ-chain locus. These mouse strains support the engraftment of a functional human immune system and permit detailed analyses of human immune biology, development and functions. In this Review, we discuss recent advances in the development and utilization of humanized mice, the lessons learnt, the remaining challenges and the promise of using humanized mice for the in vivo study of human immunology.

The aim of the study was to evaluate excessive daytime sleepiness and subjective sleep quality in patients who undergo epilepsy surgery for treatment of refractory partial seizures. Forty-eight patients were enrolled in this research study. All of them were evaluated 2 days before and 3 months after the surgery. Two questionnaires were used to assess daytime sleepiness (Epworth Sleepiness Scale [ESS]) and sleep quality (Pittsburgh Sleep Quality Index [PSQI]). Global PSQI was high (mean=5.65 SD=3.71) before the surgical procedure (P<0.001). PSQI evaluation revealed higher and statistically significant scores in three components as well as in the global score, when analyzed by predominance of daytime or nocturnal seizures. ESS and PSQI scores were also analyzed by gender, antiepileptic drug class, age, and seizure frequency, with no significant differences. We concluded that patients with partial recurrent seizures of temporal origin have poor subjective sleep quality that improves significantly after epilepsy surgery., (2009 Elsevier Inc. All rights reserved.)

The Locus Control Region (LCR) requires intronic elements within beta-globin transgenes to direct high level expression at all ectopic integration sites. However, these essential intronic elements cannot be transmitted through retrovirus vectors and their deletion may compromise the therapeutic potential for gene therapy. Here, we systematically regenerate functional beta-globin intron 2 elements that rescue LCR activity directed by 5'HS3. Evaluation in transgenic mice demonstrates that an Oct-1 binding site and an enhancer in the intron cooperate to increase expression levels from LCR globin transgenes. Replacement of the intronic AT-rich region with the Igmu 3'MAR rescues LCR activity in single copy transgenic mice. Importantly, a combination of the Oct-1 site, Igmu 3'MAR and intronic enhancer in the BGT158 cassette directs more consistent levels of expression in transgenic mice. By introducing intron-modified transgenes into the same genomic integration site in erythroid cells, we show that BGT158 has the greatest transcriptional induction. 3D DNA FISH establishes that induction stimulates this small 5'HS3 containing transgene and the endogenous locus to spatially reorganize towards more central locations in erythroid nuclei. Electron Spectroscopic Imaging (ESI) of chromatin fibers demonstrates that ultrastructural heterochromatin is primarily perinuclear and does not reorganize. Finally, we transmit intron-modified globin transgenes through insulated self-inactivating (SIN) lentivirus vectors into erythroid cells. We show efficient transfer and robust mRNA and protein expression by the BGT158 vector, and virus titer improvements mediated by the modified intron 2 in the presence of an LCR cassette composed of 5'HS2-4. Our results have important implications for the mechanism of LCR activity at ectopic integration sites. The modified transgenes are the first to transfer intronic elements that potentiate LCR activity and are designed to facilitate correction of hemoglobinopathies using single copy vectors., Competing Interests: The authors have declared that no competing interests exist.

Patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE/HS) have a distinct neuropsychological profile, but there is still debate on whether executive dysfunction is part of this profile and also whether temporal lobe surgery can modify this dysfunction., Objective: To study the presence and reversibility of executive dysfunction in patients with unilateral TLE/HS., Methods: Twenty-five patients with refractory seizures due to TLE/HS underwent presurgical evaluation which included the application of the Wiconsin Card Sorting Test (WCST). Nineteen were re-evaluated in follow up, at least 6 months after selective amygdalo-hippocampectomy (SAH). Twenty-two control subjects matched for age and education also performed the WCST., Results: Sixteen of the 25 patients (64%) completed fewer than four categories in the WCST whereas only 4 of the 22 controls (18%) did not complete at least four categories (p<0.005). In addition, the performance of the patients involved significantly more perseverative responses and errors compared to controls. The patient group demonstrated significant post-operative improvement in many measures of the WCST following SAH., Conclusions: These findings support the presence of executive dysfunction in patients with TLE/HS and suggest that such dysfunction can be partially reversed by selective resection of epileptogenic mesial temporal structures.

Aim: Terminology, concept, pathology and phisiopathology, clinical presentation, imaging diagnosis and treatment of the giant intracranial aneurysms are reviewed., Development: Saccular, fusiform, dissecting and serpentine giant aneurysms are discussed. Giant saccular aneurysms are developed from small regular congenital lesions growing far away of their critical rupture size due to the reinforcement of their wall. Fusiform and dissecting aneurysms are formed after a wide rupture of some of their wall layers and, therefore, both of them are considered to have some similarities. Finally, serpentine aneurysms are rare lesions and their growing mechanism is still under discussion., Conclusion: Any type of giant aneurysm represents a great deal for the neurosurgical management.

Object: The aim of this study was to compare seizure and memory outcome in patients with medically refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS) treated using an anterior temporal lobectomy (ATL) or a selective amygdalohippocampectomy (SA)., Methods: Surgical outcome data were prospectively collected for 2 to 11 years in 161 consecutive patients with MTLE/ HS. Eighty patients underwent an ATL and 81 an SA. Seizure control achieved with each technique was compared using the Engel classification scheme. Postoperative memory testing was performed in 86 patients (53%). At the last follow up, 72% of the patients who had undergone an ATL (mean follow up 6.7 years) and 71% of those who had undergone an SA (mean follow up 4.5 years) were seizure free (Engle Class IA). Estimated survival in patients in Engel Classes I, IA, and I and II combined did not differ between the two surgical techniques. Preoperatively, 58% of the patients had verbal memory scores one standard deviation (SD) below the normal mean. One third of the patients with preoperative scores in the normal range worsened after surgery, although this outcome was not related to the surgical technique. In contrast, one third of those whose preoperative scores were less than -1 SD experienced improvement after surgery. Nine (18%) of the 50 patients whose left side had been surgically treated improved their verbal memory scores by more than one SD. Seven (78%) of these nine underwent an SA (p = 0.05)., Conclusions: Both ATL and SA can lead to similar favorable seizure control in patients with MTLE/HS. Preliminary data suggest that postoperative verbal memory scores may improve in patients who undergo selective resection of a sclerotic hippocampus in the dominant temporal lobe.

This study compared Hispanic children (ages 7 to 11) with combined type (CT, n=33) and inattentive type (IT, n=21) attention deficit hyperactivity disorder (ADHD) and a control group (n=25) on time-estimation and time-reproduction tasks. The ADHD groups showed larger errors in time reproduction but not in time estimation than the control group, and the groups did not differ from each other on their performance on this task. Individual differences could not be accounted for by oppositional-defiance ratings and low math or reading scores. Although various measures of executive functioning did not make significant unique contributions to time estimation performance, those of interference control and nonverbal working memory did so to the time-reproduction task. Findings suggest that ADHD is associated with a specific impairment in the capacity to reproduce rather than estimate time durations and that this may be related to the children's deficits in inhibition and working memory.

Purpose: Surgical results in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS) are often reported in conjunction with other etiologies of TLE., Methods: We prospectively collected surgical outcome data for 2 to 11 years for 134 consecutive patients who specifically had MTLE and unilateral HS, according to magnetic resonance imaging (MRI) and confirmed by histopathology. Sixty-five had postoperative neuropsychological testing. Outcome was analyzed by using Engel's classification (a) through Kaplan-Meier estimated survival curves (as a function of the time to seizure recurrence), (b) as percentage of patients in each outcome class on a yearly basis, and (c) at the last updated follow-up., Results: Kaplan-Meier estimates of complete seizure freedom (Engel's class IA) for years 1, 2, 5, and 10 were 85%, 77%, 74%, and 66%, and of Engel's class I were 89%, 86%, 83%, and 81%. Only nine (6.7%) patients had outcome classes III or IV at any point during follow-up. Of the patients tested, 26% of those operated on the left side and 22% of those operated on the right had postoperative decline of >1 SD in verbal or visual memory, respectively., Conclusions: High rates of seizure freedom can be obtained and remain stable over the years in patients operated on for unilateral MTLE/HS, even in countries with limited resources.