Miracle-dz/UniFAR-FTUs huggingface dataset:
Non-pharmacological treatments for pediatric refractory epilepsies

ABSTRACT Introduction Antiseizure medications (ASMs) are the primary treatment option for epilepsies of wide etiologies, however, about 10–20% of children do not gain sustained seizure control and in this case, it is worth investigating ‘alternative’ therapeutic approaches aside from ASMs. Nowadays, non-pharmacological strategies for epilepsy treatment encompass dietary interventions, neurostimulation-based techniques, and biobehavioral approaches. Areas covered A search on PubMed database was conducted. Experimental and clinical studies, as well as meta-analysis and structured reviews on the latest non-pharmacological treatments for drug-resistant epilepsy (DRE) in children, were included. Special attention is given to the efficacy and tolerability outcomes, trying to infer the role novel approaches may have in the future. Expert opinion The large heterogeneity of primary clinical outcomes and the unavoidable subjective response of each patient to treatments prevents Researchers from the identification of a single, reliable, approach to treat DRE. The understanding of fine pathophysiologic processes is giving the way to the use of alternative therapies, such as the well-known ketogenic diet, in a ‘personalized’ view of treatment. The goal is to apply the non-pharmacological treatment most suitable for the patients sake.
Vertical ridge augmentation feasibility using unfixed collagen membranes and particulate bone substitutes: A 1‐ to 7‐year retrospective single‐cohort observational study

Abstract Aim To determine whether vertical ridge augmentation (VRA) can be obtained through guided bone regeneration (GBR) using exclusively resorbable collagen membranes and particulate bone substitutes without additional stabilization. Materials and Methods This study retrospectively examined 22 participants who underwent VRA with staged or simultaneous implant placement. The vertical defects of all participants were filled with particulate bone substitutes and covered with resorbable collagen membranes. The augmented sites were stabilized with unfixed collagen membranes and the flap without any additional fixation. The augmented tissue height was assessed using cone‐beam computed tomography at baseline, immediately after surgery, and at annual follow‐ups. Results The vertical bone gain of the 22 augmented sites amounted to 6.48 ± 2.19 mm (mean ± SD) immediately after surgery and 5.78 ± 1.72 mm at 1‐ to 7‐year follow‐up. Of the 22 augmented sites, 18 exhibited changes of less than 1 mm, while the other 4 showed changes of greater than 1 mm. Histological observation of three representative cases revealed new bone apposition on the remaining material. Conclusion The present findings indicate that GBR procedures using exclusively collagen membranes and particulate biomaterials without any additional fixation are feasible options for VRA.
Comparison of the Respiratory Resistomes and Microbiota in Children Receiving Short versus Standard Course Treatment for Community-Acquired Pneumonia

Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. ABSTRACT Pediatric community-acquired pneumonia (CAP) is often treated with 10 days of antibiotics. Shorter treatment strategies may be effective and lead to less resistance. The impact of duration of treatment on the respiratory microbiome is unknown. Data are from children (n = 171), ages 6 to 71 months, enrolled in the SCOUT-CAP trial (NCT02891915). Children with CAP were randomized to a short (5 days) versus standard (10 days) beta-lactam treatment strategy. Throat swabs were collected at enrollment and the end of the study and used for shotgun metagenomic sequencing. The number of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) was significantly lower in children receiving the short compared to standard treatment strategy at the end of the study (Wilcoxon rank sum test, P < 0.05 for each). Wilcoxon effect sizes were small for beta-lactam (r: 0.15; 95% confidence interval [CI], 0.01 to 0.29) and medium for multidrug efflux RGPC (r: 0.23; 95% CI, 0.09 to 0.37). Analyses comparing the resistome at the beginning and end of the trial indicated that in contrast to the standard strategy group, the resistome significantly differed in children receiving the short course strategy. Relative abundances of commensals such as Neisseria subflava were higher in children receiving the standard strategy, and Prevotella species and Veillonella parvula were higher in children receiving the short course strategy. We conclude that children receiving 5 days of beta-lactam therapy for CAP had a significantly lower abundance of antibiotic resistance determinants than those receiving standard 10-day treatment. These data provide an additional rationale for reductions in antibiotic use when feasible. IMPORTANCE Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. We examined relationships between the duration of antibiotic treatment and its impact on resistance genes and bacteria in the respiratory microbiome using data from a randomized controlled trial of beta-lactam therapy for pediatric pneumonia. The randomized design provides reliable evidence of the effectiveness of interventions and minimizes the potential for confounding. Children receiving 5 days of therapy for pneumonia had a lower prevalence of two different types of resistance genes than did those receiving the 10-day treatment. Our data also suggest that children receiving longer durations of therapy have a greater abundance of antibiotic resistance genes for a longer period of time than do children receiving shorter durations of therapy. These data provide an additional rationale for reductions in antibiotic use.
Characteristics of natural immunity to SARS-CoV-2 over time in wait-listed dialysis patients and recent kidney transplant recipients

Studies in nontransplant populations [1–7] have demonstrated waning natural immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over time; however, the immune response in kidney transplant recipients, while known to be attenuated, is less well described [8–10]. The impact of immunosuppression, specifically induction immunotherapy, in patients with end-stage kidney disease (ESKD) has not been studied. Compared with vaccination, kidney transplant patients with a history of coronavirus disease 2019 (COVID-19) illness have much higher titers of antireceptor binding domain (RBD) antibody levels and neutralizing antibodies [11]. In this article, we describe the changes observed in the antibodies to the RBD and to neutralizing antibodies in dialysis patients with COVID-19 illness with and without exposure to induction immunosuppression.
Genomic signatures for latitudinal selection in the tropical eel Anguilla marmorata

Selection acting across environmental gradients, such as latitudes, can cause spatial structuring of genomic variants even within panmictic populations. In this study, we focused on the within‐generation latitudinal selection between northernmost and southernmost individuals of the North Pacific population of a tropical eel Anguilla marmorata, which shares its northernmost distribution with a temperate eel Anguilla japonica. Whole‐genome sequencing data indicated that the northernmost and southernmost individuals of A. marmorata belong to a single panmictic population, as suggested by previous studies. On the contrary, parts of genomic regions across multiple chromosomes exhibited significant genetic differentiation between the northernmost and southernmost individuals, and in these genomic regions, the genotypes of the northernmost individuals were similar to those of A. japonica. These findings suggested within‐generation latitudinal selection of A. marmorata, which might have led to genetic closeness between northernmost A. marmorata and A. japonica.
Neurogenetic Heterochrony in Chick, Lizard, and Rat Mapped with Wholemount Acetylcholinesterase and the Prosomeric Model

In the developing brain, the phenomenon of neurogenesis is manifested heterotopically, that is, much the same neurogenetic steps occur at different places with a different timetable. This is due apparently to early molecular regionalization of the neural tube wall in the anteroposterior and dorsoventral dimensions, in a checkerboard pattern of more or less deformed quadrangular histogenetic areas. Their respective fate is apparently specified by a locally specific combination of active/repressed genes known as “molecular profile. ” This leads to position-dependent differential control of proliferation, neurogenesis, differentiation, and other aspects, eventually in a heterochronic manner across adjacent areal units with sufficiently different molecular profiles. It is not known how fixed these heterochronic patterns are. We reexamined here comparatively early patterns of forebrain and hindbrain neurogenesis in a lizard (Lacerta gallotia galloti), a bird (the chick), and a mammal (the rat), as demonstrated by activation of acetylcholinesterase (AChE). This is an early marker of postmitotic neurons, which leaves unlabeled the neuroepithelial ventricular cells, so that we can examine cleared wholemounts of the reacted brains to have a birds-eye view of the emergent neuronal pattern at each stage. There is overall heterochrony between the basal and alar plates of the brain, a known fact, but, remarkably, heterochrony occurs even within the precocious basal plate among its final anteroposterior neuromeric subdivisions and their internal microzonal subdivisions. Some neuromeric units or microzones are precocious, while others follow suit without any specific spatial order or gradient; other similar neuromeric units remain retarded in the midst of quite advanced neighbors, though they do produce similar neurogenetic patterns at later stages. It was found that some details of such neuromeric heterochrony are species-specific, possibly related to differential morphogenetic properties. Given the molecular causal underpinning of the updated prosomeric model used here for interpretation, we comment on the close correlation between some genetic patterns and the observed AChE differentiation patterns.
Barriers and facilitators to family caregiver training during home health care: A multisite qualitative analysis

During Medicare home health care (HHC), family caregiver assistance is often integral to implementing the care plan and avoiding readmission. Family caregiver training delivered by HHC clinicians (nurses and physical therapists [PTs]) helps ensure caregivers' ability to safely assist when HHC staff are not present. Yet, family caregiver training needs often go unmet during HHC, increasing the risk of adverse patient outcomes. There is a critical knowledge gap regarding challenges HHC clinicians face in providing necessary family caregiver training.
Dextromethorphan reduces prenatal lipopolysaccharide exposure‐induced dopaminergic neuronal loss and cytokine changes in offspring

Maternal infection during pregnancy may affect fetal brain development and increase the risk of developing neurological and mental disorders later in life in offspring. In this study, we used low‐dose lipopolysaccharide (LPS) injection to mimic mild maternal infection at a critical time window for fetal dopamine (DA) and serotonin (5‐HT) neuron development. The affected offspring exhibited reduction of dopaminergic and serotonergic neurons and anxiety‐ and depression‐related behaviors in adulthood. In the current study, we evaluated whether dextromethorphan (DM, 30 mg/kg), an over‐the‐counter antitussive drug with anti‐inflammatory and neuroprotective properties, could reduce the adverse effects of maternal infection mimicked by LPS exposure. We discovered that DM application did not change the baseline serum interleukin‐6 (IL‐6) and tumor necrosis factor α (TNFα) levels in the LPS‐exposed offspring. However, DM treatment could reduce the heightened immune responses induced by a postnatal LPS challenge test in prenatal LPS‐exposed offspring. The neuroprotective effect of DM was only seen in DA neurons but not in 5‐HT neurons. We concluded that DM treatment can partially protect the offspring against the adverse effects of LPS‐induced maternal immune activation. The reduction in heightened immune responses and dopaminergic neuronal loss in LPS‐exposed offspring could potentially reduce the risk of DA‐related neurological and psychiatric disorders later in life.
Long-Term Exercise Intervention in Patients with McArdle Disease: Clinical and Aerobic Fitness Benefits

ABSTRACT Introduction The long-term effects of exercise in patients with McArdle disease—the paradigm of “exercise intolerance”—are unknown. This is an important question because the severity of the disease frequently increases with time. Purpose This study aimed to study the effects of a long-term exercise intervention on clinical and fitness-related outcomes in McArdle patients. Methods Seventeen patients (exercise group: n = 10, 6 male, 38 ± 18 yr; control: n = 7, 4 male, 38 ± 18 yr) participated in a 2-yr unsupervised intervention including moderate-intensity aerobic (cycle-ergometer exercise for 1 h) and resistance (high load–low repetition circuit) training on 5 and 2–3 d·wk−1, respectively. Patients were assessed at baseline and postintervention. Besides safety, outcomes included clinical severity (e.g., exercise intolerance features) on a 0–3 scale (primary outcome), and aerobic fitness, gross muscle efficiency, and body composition (total/regional fat, muscle, and bone mass; secondary outcomes). Results The exercise program was safe and resulted in a reduction of 1 point (−1.0; 95% confidence interval, −1.6 to −0.5; P = 0.025) in clinical severity versus the control group, with 60% of participants in the exercise group becoming virtually asymptomatic and with no functional limitation in daily life activities. Compared with controls, the intervention induced significant and large benefits (all P < 0.05) in the workload eliciting the ventilatory threshold (both in absolute (watts, +37%) and relative units (watts per kilogram of total body mass or of lower-limb muscle mass, +44%)), peak oxygen uptake (in milliliters per kilogram per minute, +28%), and peak workload (in absolute (+27%) and relative units (+33%)). However, no significant changes were found for muscle efficiency or for any measure of body composition. Conclusions A 2-yr unsupervised intervention including aerobic and resistance exercise is safe and induces major benefits in the clinical course and aerobic fitness of patients with McArdle disease.
Effectiveness of Pneumococcal Conjugate Vaccination Against Virus-Associated Lower Respiratory Tract Infection Among Adults: A Case-Control Study

Abstract Background Interactions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses. Methods We undertook a case-control study among adults at Kaiser Permanente Southern California between 2015 and 2019. Case patients had diagnoses of lower respiratory tract infection (LRTI; including pneumonia or nonpneumonia LRTI diagnoses), with viral infections detected by multiplex polymerase chain reaction testing. Controls without LRTI diagnoses were matched to case patients by demographic and clinical attributes. We measured vaccine effectiveness (VE) for 13-valent (PCV13) against virus-associated LRTI by determining the adjusted odds ratio for PCV13 receipt, comparing case patients and controls. Results Primary analyses included 13 856 case patients with virus-associated LRTI and 227 887 matched controls. Receipt of PCV13 was associated with a VE of 24.9% (95% confidence interval, 18.4%–30.9%) against virus-associated pneumonia and 21.5% (10.9%–30.9%) against other (nonpneumonia) virus-associated LRTIs. We estimated VEs of 26.8% (95% confidence interval, 19.9%–33.1%) and 18.6% (9.3%–27.0%) against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses but not respiratory syncytial virus or adenoviruses. Conclusions Among adults, PCV13 conferred moderate protection against virus-associated LRTI. The impacts of pneumococcal conjugate vaccines may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.
The niacin receptor HCAR2 modulates microglial response and limits disease progression in a mouse model of Alzheimer’s disease

Increased dietary intake of niacin has been correlated with reduced risk of Alzheimer’s disease (AD). Niacin serves as a high-affinity ligand for the receptor HCAR2 (GPR109A). In the brain, HCAR2 is expressed selectively by microglia and is robustly induced by amyloid pathology in AD. The genetic inactivation of Hcar2 in 5xFAD mice, a model of AD, results in impairment of the microglial response to amyloid deposition, including deficits in gene expression, proliferation, envelopment of amyloid plaques, and uptake of amyloid-β (Aβ), ultimately leading to exacerbation of amyloid burden, neuronal loss, and cognitive deficits. In contrast, activation of HCAR2 with an FDA-approved formulation of niacin (Niaspan) in 5xFAD mice leads to reduced plaque burden and neuronal dystrophy, attenuation of neuronal loss, and rescue of working memory deficits. These data provide direct evidence that HCAR2 is required for an efficient and neuroprotective response of microglia to amyloid pathology. Administration of Niaspan potentiates the HCAR2-mediated microglial protective response and consequently attenuates amyloid-induced pathology, suggesting that its use may be a promising therapeutic approach to AD that specifically targets the neuroimmune response. Description The niacin receptor (HCAR2) modulates the microglia response to amyloid pathology and affects disease progression in a mouse model of Alzheimer’s disease. Targeting microglia with niacin Microglia have been shown to contribute in Alzheimer’s disease (AD) pathophysiology. However, the role of these cells remains to be completely elucidated. Here, Moutinho et al. investigated the mechanisms mediating the association between dietary intake of nicotinic acid (niacin) and the reduced risk of developing AD. The expression of niacin receptor HCAR2 is increased in brain from patients with AD and in rodent models. Hcar2 inactivation in AD mice exacerbated cognitive impairments and amyloid-β burden, whereas HCAR2 activation using the FDA-approved drug Niaspan had protective and therapeutic effects in mice by modulating the microglia response to amyloid pathology. The results suggest that modulating microglia activity through HCAR2 might be effective for preventing or treating AD.
Cleft complications: Severely rotated maxillary permanent central incisors

The maxillary permanent central incisor (MPCI) has been reported to be rotated in up to 96% of cleft patients. A severely rotated MPCI is highly visible when smiling, drawing attention to a repaired cleft lip, and is often the main presenting complaint of a patient with cleft lip and palate attending for orthodontic treatment. The benefit of interceptive orthodontic treatment to alleviate these concerns must be weighed up against the consequences of adding to the already substantial orthodontic burden likely to be faced by these patients. Despite the high prevalence of this dental abnormality among cleft patients, there is little published in the literature regarding this type of malocclusion. This paper explores the aetiology, presentation and management of this condition, using examples from cases treated within our department. In addition, the commonly found pre-existing anomaly of a short root length is discussed, in combination with the implications this may have upon orthodontic treatment planning for a rotated MPCI.
Color preference and manual laterality in the emperor tamarin (Saguinus imperator)

The current research focuses on color preference between red and green stimuli and manual laterality in the emperor tamarin (Saguinus imperator). Trichromacy in primates has been related to a foraging advantage allowing frugivore primates to distinguish ripe from unripe fruits as well to socio‐sexual communication, as trichromats would be advantaged in recognizing social and sexual signals. As warm colors can affect the emotive state of the subjects, leading to the activation of one hemisphere over the other (e.g., right hemisphere), this could lead to behavioral lateralization. Thus, studying of hand preference may be relevant when testing color preference. Nine adult zoo emperor tamarins were involved and the study aimed to investigate the preference between red, green, and white cones as well as manual laterality. Tamarins were provided with pairs of red‐green, red‐white, and green‐white combinations of cones. Ten 30‐min sessions per combination were carried out and data on the interaction with one of the two cones of each apparatus were collected to assess subjects' color preference. We also recorded the hand used by each subject during the interaction with cones of different colors and the position of the apparatus in respect to the tamarin. We found no preferences for colored versus white cones. Similarly, we reported no group‐level preferences within different color combinations, whereas individual‐level preferences were found when considering all choices. Finally, we found that red cones elicited a left‐hand preference, suggesting a right‐hemisphere involvement in the presence of red cones. Although we do not have genetic data on trichromat and dichromat females, the tendency to use the left hand when interacting with red stimuli provides further evidence that warm colors can influence the emotive state of the perceiver, affecting their manual lateralization.
A dynamic air–liquid interface system for in vitro mimicking of the nasal mucosa

The development of an in vitro 3D model for the growth of the nasal mucosa cells can improve the therapy and the study of pathological states for subjects with chronic airway conditions. We have previously characterized a system consisting of a scaffold with an internal channel and a perfusion bioreactor with two independent flows provided by an external and an internal circuit, respectively. In this paper, this system was designed as a model of the nasal cavity, in which cells, grown on the inner surface of the scaffold channel, would be in contact at the same time with both culture medium, supplied by the external circuit, and air, provided with the internal flow. To ensure adequate nutrient supply to the cells in the scaffold channel, the radial diffusion of the culture medium through the porous matrix was evaluated first in qualitative and, then, in quantitative terms, demonstrating the capability of the system to control the value and direction of this flux. As a preliminary study, the culture of epithelial cells in the scaffold channel is also discussed in static, maintaining the air–liquid interface condition for up to 3 weeks. Despite minor abnormalities, such as a gap between cell layers and some detachments from the scaffold, the scaffold ensured cell survival and growth during the experimental time.
Impact of bridging with left ventricular assist device on right ventricular function following heart transplantation

Patients awaiting orthotopic heart transplantation (OHT) can be bridged utilizing a left ventricular assist device (LVAD) that reduces left ventricular filling pressures, decreases pulmonary artery wedge pressure, and maintains adequate cardiac output. This study set out to examine the poorly investigated area of if and how pre‐treatment with LVAD impacts right ventricular (RV) function following OHT.