The obesogenic maternal environment can lead to cardiac hypertrophy in the offspring. The aim of this study was to investigate whether (-)-epicatechin (Epi) modify the expression of genes related to pathological cardiac hypertrophy (CH), and its physiological pathway, in offspring obese by programing. Four groups of eight male offspring Wistar rats of 110 days were randomly selected to control groups [C and offspring of maternal obesity (MO)] or to Epi groups (C + Epi or MO + Epi). In heart tissue, we evaluated the size of the ventricular walls and cavities, presence of fibrosis, mRNA and protein of Myh6, Myh7, Anp, Bnp, Acta 1, Col1a1, Akt, and Mtor. We observed an increase of the heart weight/body ratio in groups treated with Epi. Only in MO group, heart area and its perimeter were increased, as well as Myh7 and Anp mRNA. We found a significant decrease of fibrosis area in male offspring treatment with Epi. In Epi group Anp mRNA was decreased whilst Anp protein in MO group was increased; further, a decrease in Col1a1 protein was found in MO group. In conclusion, the maternal obesity activates pathological CH markers reactivating fetal cardiac genes involved in histological changes observed in cardiac tissue. Epi treatment decreased the content of collagen area and expression of some fetal cardiac genes participating in this pathway in offspring of maternal obesity.

Background: Ischemic stroke increases the number of glial cells, such as astrocytes, and causes neuronal death, disrupting the neuron-to-glia balance, contributing to neurodegeneration. Treatment with NeuroD-adeno-associated virus (NeuroD1-AVV) may enhance neuronal transdifferentiation and improve motor function, but the optimal administration protocol for the drug has yet to be determined. Methods: Non-human primates (NHPs) underwent middle cerebral occlusion surgery. Fourteen days poststroke, subjects received NeuroD1-AVV according to two distinct protocols: Three high doses and three low doses. Neurological deficits and cognitive performance were measured using the NHP stroke scale and coloured glove shift of set task, respectively. Nine months post-stroke, NHPs were euthanized. Brains were harvested and stained for neuronal (NEUN and MAP2) and glial (GFAP, IBA1) markers using immunofluorescence techniques. Results: Our results indicate that both protocols effectively rebalance the neuron-to-glia cell ratio by decreasing GFAP+ cells in the P1 and P2 NHPS ipsilateral hemispheres. No cognitive performance differences were found across groups; however, P2 had better NHPSS outcomes from months 2 to 9. Conclusions: The findings support both injection protocols in restoring histological balance, with P2 being more effective for motor function rehabilitation. Investigations into neuronal functionality and development levels continue.

Background: Stroke therapies remain an area of ongoing research. Gene therapies offer a novel approach to repair tissue damage, particularly NeuroD1-mediated astrocyte-to-neuron conversion, which regenerates functional neurons after ischemic injury. Here, we applied NeuroD1 therapy in a non-human primates (NHPs) stroke model to evaluate its effects on corticospinal tract (CST) recovery and motor performance. Methods: Eight NHPs underwent middle cerebral artery occlusion (MCAO). Fourteen days later, six animals received intracranial NeuroD1 treatment (three high-dose, three low-dose), while two received a control solution. Neurological and functional performance were assessed daily. MRI scans were performed at baseline and at 7, 30, 90, 120, and 240 days post-MCAO, with the bilateral CST reconstructed at each time point. All procedures followed Canadian Council of Animal Care guidelines and were approved by Queen’s University’s Animal Use Subcommittee. Results: We found that NHPs receiving the control solution exhibited poorer motor recovery and minimal CST reconstruction. In contrast, those treated with a low dose of NeuroD1 demonstrated motor and functional recovery along with CST reconstruction. Notably, animals receiving the higher dose showed the most significant overall recovery including a greater CST integrity. Conclusions: NeuroD1 treatment promotes white matter tract restoration and facilitates motor recovery following stroke.

Background: Ischemic stroke often results in long-term motor impairments due to disrupted corticospinal pathways. Transcranial magnetic stimulation (TMS) motor mapping is a non-invasive technique used to assess corticospinal integrity by measuring motor evoked potentials (MEPs). This study investigates whether MEP amplitudes can predict impairment severity and functional performance in chronic stroke. Methods: Four non-human primates (NHPs) with chronic stroke (> six months) following transient right middle cerebral artery occlusion underwent TMS motor mapping using neuronavigation under ketamine anesthesia. Single pulses of TMS (50-70% of maximum stimulator output) were applied to the affected and contralesional primary motor cortices to elicit MEPs and assess cortical excitability. Intramuscular electromyography recorded muscle responses from the biceps, extensor digitorum longus, and abductor pollicis brevis. Neurological dysfunction was evaluated daily for three weeks using the NHP Stroke Scale, NHP Upper Extremity Motor Dysfunction Scale, and the primate Rankin Scale. Results: MEPs were present in NHP1, NHP3, and NHP4 but absent in NHP2. Stronger MEPs correlated with lower impairment severity and better functional performance, while NHP2 exhibited higher impairment and poorer performance. Conclusions: MEP presence and strength can serve as biomarkers of motor recovery potential, highlighting their role in assessing corticospinal integrity and functional outcomes.

To understand the potential human health effects of exposure to hazardous substances among first responders from the East Palestine train derailment, an electronic self-administered Assessment of Chemical Exposures (ACE) survey was created and available to first responders between February-March 2023. Among the 339 completed responder surveys analyzed, most reported working at least 1 day during the incident between February 3-8, 2023. Most (79%) reported inhaling, touching, or swallowing potentially harmful substances and did not report using a face mask or respirator while working (75%). Nearly half reported at least 1 new or worsening physical symptom after incident response. These findings support several recommendations to mitigate exposure to hazardous substances among first responders during future incidents, including using a hierarchy of controls framework to reduce exposure to hazards, timely communication of possible hazardous substances involved in the event, and using the Emergency Responder Health Monitoring Surveillance (ERHMS) framework.

The evaluation of services has become a common strategy in service management, and there is a wide variety of tools available. The objective was to evaluate user satisfaction at a sports center using the Net Promoter Score (NPS) and Importance-Performance Analysis (IPA) techniques, comparing the information provided by each. To this end, this study involved 1,433 users of a sports center, analyzing the responses to the NPS® tool and subsequently to the IPA tool developed ad hoc with 11 attributes. The NPS® tool revealed 29.58% detractors, 30.36% passives, and 40.06% promoters, highlighting a negative impact on the overall score. The IPA tool offered detailed insights into attributes varying across the three NPS groups, identifying four critical attributes requiring strategic attention, enabling segmented marketing strategies. This research demonstrates the complementary value of combining NPS and IPA tools for strategic service management, providing actionable insights to enhance customer satisfaction and competitive positioning.

Pain monitoring and diagnosis are crucial in seeking to improve animal welfare. This pilot study aimed to investigate the impact of long hours observation on pain assessment and the intra-observer reliability in piglets using video recording. A total of ten piglets, five from the control group (sham castration; pain-free) and five from the pain group (surgical castration; pain-state), were video-recorded immediately post-castration. The videos were randomised and assessed by an experienced observer using the Unesp-Botucatu Pig Composite Acute Pain Scale (UPAPS). The same ten videos were watched at three different times (trial initiation, half-way point, trial termination) with a four-week interval between them. During the four-week interval periods, the observer watched an additional 360 videos from another study to simulate long observation periods. For the pain group, no differences were found in the post hoc test for the UPAPS total score, and most of the UPAPS items. In contrast, for the control group, the UPAPS total score was higher at the half-way time-point, and no differences were found between UPAPS items. The intra-class correlation coefficient (ICC) inferred ‘very good’ intra-observer reliability for UPAPS total score in all time-points of assessment for both groups. Video-recorded pain assessment is a reliable method to assess pain in piglets given that observation duration for pain assessment had only minimal impact on the UPAPS total score, and no differences were found among most of the items. From an animal welfare standpoint, video-recorded pain assessment is a non-invasive method, that can be an additional asset for pain research.

Objectives/Goals: Optimal hydrocephalus treatment with permanent cerebrospinal fluid (CSF) diversion in myelomeningocele (MMC) patients is not well understood, especially how treatment response varies with time of MMC repair. We evaluate two treatment methods in this population–endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunting (VPS). Methods/Study Population: We retrospectively identified patients from St. Louis Children’s Hospital who were diagnosed with MMC prenatally and underwent either prenatal or postnatal repair and subsequently underwent permanent treatment for hydrocephalus (VPS or ETV +/- choroid plexus cauterization) between 2018 and 2024. The primary outcome was failure (defined as need for revision) of procedure and time to failure. All revisions were shunt insertions/revisions. Differences in preoperative and 6-month postoperative head circumference (HC) and WHO standard HC z-score were examined. Differences in preoperative and 6-month follow-up fronto-occipital horn ratios (FOHR), a validated age-independent measure of CSF within the brain, on CT and MRI were additionally examined. Results/Anticipated Results: Eighty-three MMC patients were identified. 46 (55%) underwent CSF diversion: 37 (80.4%, 9 pre- and 28 postnatal) VPS and 9 (19.6%, 5 pre- and 4 postnatal) ETV +/- choroid plexus cauterization. Six (16%) VPS patients required revision vs. 3 (33%) ETV patients (∆17%; 95% CI -9 – 50). Mean time to failure was longer after VPS vs. ETV (516, SD 470 vs. 34, SD 7 days) [∆482; 95% CI 163 – 800]. The decrease between pre- and postoperative FOHR was greater after VPS vs. ETV (6 mo: -0.14, SD 0.10 vs. -0.03, SD 0.07) [∆0.11; 95% CI 0.04 – 0.18]. Differences in pre- and postoperative HC were similar (VPS 5.67, SD 2.91 vs. ETV 4.04, SD 1.66 cm) [∆1.63; 95% CI -0.71 – 3.98]. Greater, but not significant, z-score decreases were seen after VPS vs. ETV (-1.04, SD 2.22 vs. -0.13, SD 1.11) [∆-0.91; 95% CI -2.68 – 0.86]. Similar trends were observed in pre- and postnatal MMC repair groups. Discussion/Significance of Impact: Failure rates in MMC-associated hydrocephalus patients were greater in the ETV group, but no definitive conclusion can be made due to imprecision. Those treated with ETV have less time to failure and smaller FOHR decreases than those treated with VPS, indicating less CSF drainage. Due to the need for more subjects, future research should be multicenter.

Gyrodactylidae Cobbold, 1864 is a monophyletic family of hyperviviparous species, with 36 genera and approximately 700 species. Here, we focused on one of these genera – namely Scleroductus Jara & Cone, 1989 – characterizing its morphological variation systematically and testing its phylogenetic position in relation to other genera in the family. We collected and describe two new species of monogenean parasites of Scleroductus infecting Neotropical freshwater catfishes in Mexico. Scleroductus veracruzano n. sp. infects Guatemalan chulín, Rhamdia guatemalensis in Veracruz, while Scleroductus oaxaqueno n. sp. infects filespine chulín, Rhamdia laticauda in Oaxaca, Mexico. Sequences of the internal transcribed spacer (ITS rDNA) and 18S rDNA were generated for both species. Phylogenetic hypotheses based on maximum likelihood and Bayesian inference analyses of 18S rDNA indicate that the two new Mexican taxa are closely related to each other, and both appear as sister species to an undescribed but molecularly characterized Scleroductus sp. infecting South American catfish, Rhamdia quelen in Brazil. Our analyses confirm the placement of Scleroductus spp. within the monophyletic family Gyrodactylidae, whose sister clade is the Oogyrodactylidae. Within Gyrodactylidae, Scleroductus spp. form a clade sister to a well-supported clade composed by members of the genera Ieredactylus, Gyrodactyloides and Laminiscus.

Quantum field theory predicts a nonlinear response of the vacuum to strong electromagnetic fields of macroscopic extent. This fundamental tenet has remained experimentally challenging and is yet to be tested in the laboratory. A particularly distinct signature of the resulting optical activity of the quantum vacuum is vacuum birefringence. This offers an excellent opportunity for a precision test of nonlinear quantum electrodynamics in an uncharted parameter regime. Recently, the operation of the high-intensity Relativistic Laser at the X-ray Free Electron Laser provided by the Helmholtz International Beamline for Extreme Fields has been inaugurated at the High Energy Density scientific instrument of the European X-ray Free Electron Laser. We make the case that this worldwide unique combination of an X-ray free-electron laser and an ultra-intense near-infrared laser together with recent advances in high-precision X-ray polarimetry, refinements of prospective discovery scenarios and progress in their accurate theoretical modelling have set the stage for performing an actual discovery experiment of quantum vacuum nonlinearity.

Adults have an interconnected lexicon in which two words are related because their referents belong to the same semantic category, because they occur in the same context, or both. This interconnection has been explored by means of the priming effect, in which people respond more rapidly to related than to unrelated words and benefit from the lexical boost when the two types of interconnections are combined. Although substantial research has reported on the memory problems of people diagnosed with Alzheimer’s disease (AD), it remains unknown whether they experience problems with related words at these levels of comprehension. This study analyzed the lexical networks of older adults with AD and typically aging (TA) adults to understand their semantic memory related to word associations. We tested combined taxonomic-thematic, purely taxonomic, and purely thematic relationships using an eye tracker to analyze fixations to a named target picture preceded by a related or unrelated prime word. Participants with TA showed a priming effect in all three types of relationships, but those with AD showed this effect only with purely thematic pairs. Words that share more than one level of relationship seem to create competition, revealing a deficit in the lexical networks of people with AD.