A 12-Month Follow-Up of PROCARE+, a Transdiagnostic, Selective, Preventive Intervention for Adolescents At-Risk for Emotional Disorders.

Few studies have reported long-term follow-up data on selective preventive interventions for adolescents. No follow-up selective preventive transdiagnostic studies for adolescents at-risk for emotional disorders, such as anxiety and depression, have been reported. To fill this gap, this study aims to provide the first follow-up assessment of a randomized controlled trial (RCT) studying selective transdiagnostic prevention in at-risk adolescents. A 12-month follow-up assessment was conducted with subjects who originally received either PROCARE (Preventive transdiagnostic intervention for Adolescents at Risk for Emotional disorders), PROCARE+, which includes the PROCARE protocol along with personalized add-on modules or an active control condition (ACC) based on emotional psychoeducation, and their respective booster session for each experimental condition. 80 subjects (47.5% girls) aged between 12 and 18 years (M = 14.62; SD 1.43) who completed these treatment conditions were available for the 12-month follow-up. The results demonstrate the superior long-term efficacy of the PROCARE+ intervention in mitigating emotional symptoms and obsessive-compulsive symptomatology compared to the PROCARE and ACC conditions, with effect sizes notably exceeding those commonly observed in preventive programs. While the three treatments demonstrated beneficial impacts, the pronounced results associated with PROCARE+ at the 12-month follow-up emphasized the importance of personalized treatment modules and the sustained benefits of booster sessions in the realm of preventive psychological interventions. The findings also highlight the potential role of add-on modules in enhancing the effects of the PROCARE+ condition.

Effect of Anti-Osteoporotic Treatments on Circulating and Bone MicroRNA Patterns in Osteopenic ZDF Rats.

Bone fragility is an adverse outcome of type 2 diabetes mellitus (T2DM). The underlying molecular mechanisms have, however, remained largely unknown. MicroRNAs (miRNAs) are short non-coding RNAs that control gene expression in health and disease states. The aim of this study was to investigate the genome-wide regulation of miRNAs in T2DM bone disease by analyzing serum and bone tissue samples from a well-established rat model of T2DM, the Zucker Diabetic Fatty (ZDF) model. We performed small RNA-sequencing analysis to detect dysregulated miRNAs in the serum and ulna bone of the ZDF model under placebo and also under anti-sclerostin, PTH, and insulin treatments. The dysregulated circulating miRNAs were investigated for their cell-type enrichment to identify putative donor cells and were used to construct gene target networks. Our results show that unique sets of miRNAs are dysregulated in the serum (n = 12, FDR < 0.2) and bone tissue (n = 34, FDR < 0.2) of ZDF rats. Insulin treatment was found to induce a strong dysregulation of circulating miRNAs which are mainly involved in metabolism, thereby restoring seven circulating miRNAs in the ZDF model to normal levels. The effects of anti-sclerostin treatment on serum miRNA levels were weaker, but affected miRNAs were shown to be enriched in bone tissue. PTH treatment did not produce any effect on circulating or bone miRNAs in the ZDF rats. Altogether, this study provides the first comprehensive insights into the dysregulation of bone and serum miRNAs in the context of T2DM and the effect of insulin, PTH, and anti-sclerostin treatments on circulating miRNAs.

Human CD4+CD45RA+ T Cells Behavior after In Vitro Activation: Modulatory Role of Vasoactive Intestinal Peptide.

Naїve CD4+ T cells, which suffer different polarizing signals during T cell receptor activation, are responsible for an adequate immune response. In this study, we aimed to evaluate the behavior of human CD4+CD45RA+ T cells after in vitro activation by anti-CD3/CD28 bead stimulation for 14 days. We also wanted to check the role of the VIP system during this process. The metabolic biomarker Glut1 was increased, pointing to an increase in glucose requirement whereas Hif-1α expression was higher in resting than in activated cells. Expression of Th1 markers increased at the beginning of activation, whereas Th17-associated biomarkers augmented after that, showing a pathogenic Th17 profile with a possible plasticity to Th17/1. Foxp3 mRNA expression augmented from day 4, but no parallel increases were observed in IL-10, IL-2, or TGFß mRNA expression, meaning that these potential differentiated Treg could not be functional. Both VIP receptors were located on the plasma membrane, and expression of VPAC2 receptor increased significantly with respect to the VPAC1 receptor from day 4 of CD4+CD45RA+ T activation, pointing to a shift in VPAC receptors. VIP decreased IFNγ and IL-23R expression during the activation, suggesting a feasible modulation of Th17/1 plasticity and Th17 stabilization through both VPAC receptors. These novel results show that, without polarizing conditions, CD4+CD45RA+ T cells differentiate mainly to a pathogenic Th17 subset and an unpaired Treg subset after several days of activation. Moreover, they confirm the important immunomodulatory role of VIP, also on naїve Th cells, stressing the importance of this neuropeptide on lymphocyte responses in different pathological or non-pathological situations.

VIP/VPAC Axis Expression in Immune-Mediated Inflammatory Disorders: Associated miRNA Signatures.

Few studies have considered immune-mediated inflammatory disorders (IMID) together, which is necessary to adequately understand them given they share common mechanisms. Our goal was to investigate the expression of vasoactive intestinal peptide (VIP) and its receptors VPAC1 and VPAC2 in selected IMID, analyze the effect of biological therapies on them, and identify miRNA signatures associated with their expression. Serum VIP levels and mRNA of VPAC and miRNA expression in peripheral blood mononuclear cells were analyzed from 52 patients with psoriasis, rheumatoid arthritis, Graves' disease, or spondyloarthritis and from 38 healthy subjects. IMID patients showed higher levels of VIP and increased expression of VPAC2 compared to controls (p < 0.0001 and p < 0.0192, respectively). Receiver operating characteristic curve analysis showed that the levels of VIP or VPAC2 expression were adequate discriminators capable of identifying IMID. Treatment of IMID patients with anti-TNFα and anti-IL12/23 significantly affected serum VIP levels. We identified miRNA signatures associated with levels of serum VIP and VPAC2 expression, which correlated with IMID diagnosis of the patients. The results indicate that the expression of VIP/VPAC2 is able of identify IMIDs and open up a line of research based on the association between the VIP/VPAC axis and miRNA signatures in immune-mediated diseases.

Reactive Extrusion as a Pretreatment in Cassava (Manihot esculenta Crantz) and Pea (Pisum sativum L.) Starches to Improve Spinnability Properties for Obtaining Fibers.

Starch is a biocompatible and economical biopolymer in which interest has been shown in obtaining electrospun fibers. This research reports that cassava (CEX) and pea (PEX) starches pretreated by means of reactive extrusion (REX) improved the starches rheological properties and the availability of amylose to obtain fibers. Solutions of CEX and PEX (30-36% w/v) in 38% v/v formic acid were prepared and the rheological properties and electrospinability were studied. The rheological values indicated that to obtain continuous fibers without beads, the entanglement concentration (Ce) must be 1.20 and 1.25 times the concentration of CEX and PEX, respectively. In CEX, a higher amylose content and lower viscosity were obtained than in PEX, which resulted in a greater range of concentrations (32-36% w/v) to obtain continuous fibers without beads with average diameters ranging from 316 ± 65 nm to 394 ± 102 nm. In PEX, continuous fibers without beads were obtained only at 34% w/v with an average diameter of 170 ± 49 nm. This study showed that starches (20-35% amylose) pretreated through REX exhibited electrospinning properties to obtain fibers, opening the opportunity to expand their use in food, environmental, biosensor, and biomedical applications, as vehicles for the administration of bioactive compounds.

Intrathecal administration of autologous mesenchymal stromal cells for spinal cord injury: Safety and efficacy of the 100/3 guideline.

BACKGROUND AIMS: Cell therapy with autologous mesenchymal stromal cells (MSCs) in patients with spinal cord injury (SCI) is beginning, and the search for its better clinical application is an urgent need. METHODS: We present a phase 2 clinical trial in patients with chronic SCI who received three intrathecal administrations of 100 x 106 MSCs and were followed for 10 months from the first administration. Efficacy analysis was performed on nine patients, and safety analysis was performed on 11 patients. Clinical scales, urodynamic, neurophysiological and neuroimaging studies were performed previous to treatment and at the end of the follow-up. RESULTS: The treatment was well-tolerated, without any adverse event related to MSC administration. Patients showed variable clinical improvement in sensitivity, motor power, spasms, spasticity, neuropathic pain, sexual function or sphincter dysfunction, regardless of the level or degree of injury, age or time elapsed from the SCI. In the course of follow-up three patients, initially classified as ASIA A, B and C, changed to ASIA B, C and D, respectively. In urodynamic studies, at the end of follow-up, 66.6% of the patients showed decrease in postmicturition residue and improvement in bladder compliance. At this time, neurophysiological studies showed that 55.5% of patients improved in somatosensory or motor-evoked potentials, and that 44.4% of patients improved in voluntary muscle contraction together with infralesional active muscle reinnervation. CONCLUSIONS: The present guideline for cell therapy is safe and shows efficacy in patients with SCI, mainly in recovery of sphincter dysfunction, neuropathic pain and sensitivity.

Cell therapy with autologous mesenchymal stromal cells in post-traumatic syringomyelia.

BACKGROUND AIMS: Recently, clinical studies show that cell therapy with mesenchymal stromal cells (MSCs) improves the sequelae chronically established in paraplegic patients, being necessary to know which of them can obtain better benefit. METHODS: We present here a phase 2 clinical trial that includes six paraplegic patients with post-traumatic syringomyelia who received 300 million MSCs inside the syrinx and who were followed up for 6 months. Clinical scales, urodynamic, neurophysiological, magnetic resonance (MR) and studies of ano-rectal manometry were performed to assess possible improvements. RESULTS: In all the cases, MR at the end of the study showed a clear reduction of the syrinx, and, at this time, signs of improvement in the urodynamic studies were found. Moreover, four patients improved in ano-rectal manometry. Four patients improved in neurophysiological studies, with signs of improvement in evoked potentials in three patients. In the American Spinal Injury Association (ASIA) assessment, only two patients improved in sensitivity, but clinical improvement in neurogenic bowel dysfunction was observed in four patients and three patients described improvement in bladder dysfunction. Spasms reduced in two of the five patients who had them previous to cell therapy, and spasticity was improved in the other two patients. Three patients had neuropathic pain before treatment, and it was reduced or disappeared completely during the study. Only two adverse events ocurred, without relation to the cell therapy. CONCLUSIONS: Cell therapy can be considered as a new alternative to the treatment of post-traumatic syringomyelia, achieving reduction of syrinx and clinical improvements in individual patients.

Pleistocene range shifts, refugia and the origin of widespread species in western Palaearctic water beetles.

Quaternary glacial cycles drove major shifts in both the extent and location of the geographical ranges of many organisms. During glacial maxima, large areas of central and northern Europe were inhospitable to temperate species, and these areas are generally assumed to have been recolonized during interglacials by range expansions from Mediterranean refugia. An alternative is that this recolonization was from non-Mediterranean refugia, in central Europe or western Asia, but data on the origin of widespread central and north European species remain fragmentary, especially for insects. We studied three widely distributed lineages of freshwater beetles (the Platambus maculatus complex, the Hydraena gracilis complex, and the genus Oreodytes), all restricted to running waters and including both narrowly distributed southern endemics and widespread European species, some with distributions spanning the Palearctic. Our main goal was to determine the role of the Pleistocene glaciations in shaping the diversification and current distribution of these lineages. We sequenced four mitochondrial and two nuclear genes in populations drawn from across the ranges of these taxa, and used Bayesian probabilities and Maximum Likelihood to reconstruct their phylogenetic relationships, age and geographical origin. Our results suggest that all extant species in these groups are of Pleistocene origin. In the H. gracilis complex, the widespread European H. gracilis has experienced a rapid, recent range expansion from northern Anatolia, to occupy almost the whole of Europe. However, in the other two groups widespread central and northern European taxa appear to originate from central Asia, rather than the Mediterranean. These widespread species of eastern origin typically have peripherally isolated forms in the southern Mediterranean peninsulas, which may be remnants of earlier expansion-diversification cycles or result from incipient isolation of populations during the most recent Holocene expansion. The accumulation of narrow endemics of such lineages in the Mediterranean may result from successive cycles of range expansion, with subsequent speciation (and local extinction in glaciated areas) through multiple Pleistocene climatic cycles.

Repeated subarachnoid administrations of autologous mesenchymal stromal cells supported in autologous plasma improve quality of life in patients suffering incomplete spinal cord injury.

BACKGROUND AIMS: Cell therapy with mesenchymal stromal cells (MSCs) offers new hope for patients suffering from spinal cord injury (SCI). METHODS: Ten patients with established incomplete SCI received four subarachnoid administrations of 30 × 106 autologous bone marrow MSCs, supported in autologous plasma, at months 1, 4, 7 and 10 of the study, and were followed until the month 12. Urodynamic, neurophysiological and neuroimaging studies were performed at months 6 and 12, and compared with basal studies. RESULTS: Variable improvement was found in the patients of the series. All of them showed some degree of improvement in sensitivity and motor function. Sexual function improved in two of the eight male patients. Neuropathic pain was present in four patients before treatment; it disappeared in two of them and decreased in another. Clear improvement in bladder and bowel control were found in all patients suffering previous dysfunction. Before treatment, seven patients suffered spasms, and two improved. Before cell therapy, nine patients suffered variable degree of spasticity, and 3 of them showed clear decrease at the end of follow-up. At this time, nine patients showed infra-lesional electromyographic recordings suggesting active muscle reinnervation, and eight patients showed improvement in bladder compliance. After three administrations of MSCs, mean values of brain-derived neurotrophic factor, glial-derived neurotrophic factor, ciliary neurotrophic factor, and neurotrophin 3 and 4 showed slight increases compared with basal levels, but without statistically significant difference. CONCLUSIONS: Administration of repeated doses of MSCs by subarachnoid route is a well-tolerated procedure that is able to achieve progressive and significant improvement in the quality of life of patients suffering incomplete SCI.

Bilingualism Influences Structural Indices of Interhemispheric Organization.

Bilingualism represents an interesting model of possible experience-dependent alterations in brain structure. The current study examines whether interhemispheric adaptations in brain structure are associated with bilingualism. Corpus callosum volume and cortical thickness asymmetry across 13 regions of interest (selected to include critical language and bilingual cognitive control areas) were measured in a sample of Spanish-English bilinguals and age- and gender-matched monolingual individuals (N = 39 per group). Cortical thickness asymmetry of the anterior cingulate region differed across groups, with thicker right than left cortex for bilinguals and the reverse for monolinguals. In addition, two adjacent regions of the corpus callosum (mid-anterior and central) had greater volume in bilinguals. The findings suggest that structural indices of interhemispheric organization in a critical cognitive control region are sensitive to variations in language experience.

On-Board Detection of Pedestrian Intentions.

Avoiding vehicle-to-pedestrian crashes is a critical requirement for nowadays advanced driver assistant systems (ADAS) and future self-driving vehicles. Accordingly, detecting pedestrians from raw sensor data has a history of more than 15 years of research, with vision playing a central role. During the last years, deep learning has boosted the accuracy of image-based pedestrian detectors. However, detection is just the first step towards answering the core question, namely is the vehicle going to crash with a pedestrian provided preventive actions are not taken? Therefore, knowing as soon as possible if a detected pedestrian has the intention of crossing the road ahead of the vehicle is essential for performing safe and comfortable maneuvers that prevent a crash. However, compared to pedestrian detection, there is relatively little literature on detecting pedestrian intentions. This paper aims to contribute along this line by presenting a new vision-based approach which analyzes the pose of a pedestrian along several frames to determine if he or she is going to enter the road or not. We present experiments showing 750 ms of anticipation for pedestrians crossing the road, which at a typical urban driving speed of 50 km/h can provide 15 additional meters (compared to a pure pedestrian detector) for vehicle automatic reactions or to warn the driver. Moreover, in contrast with state-of-the-art methods, our approach is monocular, neither requiring stereo nor optical flow information.

Neurostructural correlates of consistent and weak handedness.

Various cognitive differences have been reported between consistent and weak handers, but little is known about the neurobiological factors that may be associated with this distinction. The current study examined cortical structural lateralization and corpus callosum volume in a large, well-matched sample of young adults (N = 164) to explore potential neurostructural bases for this hand group difference. The groups did not differ in corpus callosum volume. However, at the global hemispheric level, weak handers had reduced or absent asymmetries for grey and white matter volume, cortical surface area, thickness, and local gyrification, relative to consistent handers. Group differences were also observed for some regional hemispheric asymmetries, the most prominent of which was reduced or absent gyrification asymmetry for weak handers in a large region surrounding the central sulcus and extending into parietal association cortex. The findings imply that variations in handedness strength are associated with differences in structural lateralization, not only in somatomotor regions, but also in areas associated with high level cognitive control of action.

Pedestrian Detection at Day/Night Time with Visible and FIR Cameras: A Comparison.

Despite all the significant advances in pedestrian detection brought by computer vision for driving assistance, it is still a challenging problem. One reason is the extremely varying lighting conditions under which such a detector should operate, namely day and nighttime. Recent research has shown that the combination of visible and non-visible imaging modalities may increase detection accuracy, where the infrared spectrum plays a critical role. The goal of this paper is to assess the accuracy gain of different pedestrian models (holistic, part-based, patch-based) when training with images in the far infrared spectrum. Specifically, we want to compare detection accuracy on test images recorded at day and nighttime if trained (and tested) using (a) plain color images; (b) just infrared images; and (c) both of them. In order to obtain results for the last item, we propose an early fusion approach to combine features from both modalities. We base the evaluation on a new dataset that we have built for this purpose as well as on the publicly available KAIST multispectral dataset.

MiR-144-5p and miR-21-5p do not drive bone disease in a mouse model of type 1 diabetes mellitus.

The increased risk of fractures in patients with type 1 diabetes mellitus (T1DM) is nowadays well recognized. However, the exact mechanism of action of diabetic bone disease has not been fully elucidated. MicroRNAs (miRNAs) are gene regulators that operate post-transcriptionally and have been implicated in the development of various metabolic disorders including T1DM. Previous studies have implicated a role for miR-144-5p and miR-21-5p, which are involved in controlling oxidative stress by targeting Nrf2, in T1DM. To date, it is unclear whether miR-144-5p and miR-21-5p affect bone health in T1DM. Thus, this study aimed to investigate the influence of miR-144-5p and miR-21-5p knockdown in the development of bone disease in T1DM male mice. Therefore, T1DM was induced in 10-wk-old male mice using streptozotocin (STZ). One week later, after development of hyperglycemia, antagomir-144-5p and antagomir-21-5p or their non-targeting control were administered at 10 mg/kg BW once a week until the end of the experiment. At 14 wk of age, glucose levels, bone, and fat mass were analyzed. The results revealed that treating T1DM male mice with antagomir-144-5p and antagomir-21-5p did not protect against diabetes development or bone loss, despite the successful downregulation of the miRNAs and the normalization of Nrf2 mRNA levels in bone tissue. Histological and serological parameters of bone formation or resorption were not altered by the antagomir treatment. Finally, we measured the expression of miRNA-144-5p or miRNA-21-5p in the serum of 30 individuals with T1DM and compared them to non-diabetic controls, but did not find an altered expression of either miRNA. In conclusion, the knockdown of miR-144-5p and miR-21-5p does not affect STZ-induced diabetes development or loss of bone mass in male mice. However, it does normalize expression of the anti-oxidant factor Nrf2 in diabetic bone tissue.

Exposure to Ozone Downregulates Bcl-2 and Increases Executing Caspases-3 and -8 in the Hippocampus, Frontal Cortex, and Cerebellum of Rats.

Introduction Ozone (O3) is one of the most prevalent atmospheric pollutants, arising from a photochemical reaction between volatile organic compounds (VOC), nitrogen oxides (NOx), and sunlight. O3 triggers oxidative stress, resulting in lipid oxidation, inflammation, alterations in metabolic and cellular signaling, and potentially initiating cell death in vulnerable brain regions. Inflammation and oxidative stress are recognized for their ability to induce cell death, primarily through the apoptosis pathway, involving various proteins that participate in this process via two pathways: intrinsic and extrinsic. Objective This study aims to identify the expression of pro-apoptotic proteins and Bcl-2 in the frontal cortex, cerebellum, and hippocampus of rats exposed to O3 acutely. Methods Two groups of 20 Wistar rodents (250-300 g) were established. The control group (n=10) was exposed to unrestricted polluted air for 12 hours, while the experimental group (n=10) was exposed to 1 ppm of O3. After exposure, the animals were sacrificed for immunofluorescence and Western blot analysis. Using a t-test, the arbitrary units of pro-apoptotic proteins and Bcl-2 were compared between the two groups. Results Significant increases in caspase-8 and caspase-3 activation were found in the O3-exposed group compared to the control group, specifically in the frontal cortex, cerebellum, and hippocampus. Additionally, notable changes in Bcl-2 expression were observed in these brain regions. The TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay further indicated significant differences in immunopositivity between the groups in the same areas. However, intrinsic apoptotic proteins such as Bax, VDAC1, and cytochrome-c did not show significant differences between the groups within these structures. Western blot analyses aligned with the immunofluorescence results, showing statistically significant concentrations of caspase-8 in the cerebellum, caspase-3 in the hippocampus, and Bcl-2 in the frontal cortex in the O3 exposed group. Conversely, proteins like Bax, cytochrome-c, and VDAC1 did not exhibit significant differences in all analyzed structures. Conclusions This study demonstrates that acute exposure to 1 ppm of ozone can trigger neuronal apoptosis in the frontal cortex, hippocampus, and cerebellum of rats, primarily through the activation of the extrinsic apoptosis pathway via caspase-8 and caspase-3. Additionally, it causes a reduction in Bcl-2 expression, an essential antiapoptotic protein. Despite not observing the activation of intrinsic pathway proteins like BAX, VDAC, or cytochrome-c, the study suggests that chronic O3 exposure might promote cell death by activating this pathway, requiring further long-term research.

Clinical Outcomes of Non-Stent-Based Interventions for Symptomatic Below-the-Knee Peripheral Artery Disease in the Excellence in Peripheral Artery Disease (XLPAD) Registry.

For endovascular treatment of below-the-knee (BTK) peripheral artery disease (PAD), independently adjudicated real-world outcomes comparing non-stent-based balloon angioplasty (percutaneous transluminal angioplasty) and adjunctive treatments with or without a concomitant ipsilateral femoropopliteal (FP) artery intervention are scarce. A total of 1,060 patients from the multicenter XLPAD registry who underwent non-stent-based BTK PAD intervention between 2006 and 2021 were included. The primary outcome was the 1-year incidence of major adverse limb events (MALEs), a composite of all-cause death, any amputation, or clinically driven repeat revascularization. A total of 566 patients underwent BTK and 494 BTK + FP interventions; 72% were men, with a mean age of 68.4 ± 10.9 years. Diabetes mellitus was more prevalent in the BTK-only group (76.5% vs 69%, p = 0.006). Mean Rutherford class was 4.2 ± 1.18; chronic limb-threatening ischemia was more frequent in the BTK group (55.3% vs 49%, p = 0.040). Moderate to severe calcification was more frequent in the BTK + FP group (21.2% vs 27.1%, p = 0.024), as was lesion length (110.6 ± 77.3 vs 135.4 ± 86.3 mm, p <0.001). Nearly 81% of lesions were treated with percutaneous transluminal angioplasty. Drug-coated balloon (1.6% vs 14%, p <0.001) and atherectomy (38% vs 58.5%, p <0.001) use was more frequent in the BTK + FP group. The rate of procedural success was higher in the BTK + FP group (86% vs 91%, p = 0.009), with amputation being the most common complication at 3.3% within 30 days after the procedure. The rates of 1-year MALE (21.2% vs 22.3%, p = 0.675) and mortality (4.6% vs 3.4%, p = 0.3) were similar between the BTK and BTK + FP groups. Nonstent treatment for BTK PAD with concomitant FP intervention leads to high procedural success and similar rates of 1-year MALE compared with isolated BTK intervention. Condensed Abstract: The vast majority of below-the-knee (BTK) peripheral artery disease (PAD) interventions are performed with balloon angioplasty. Presence of inflow femoropopliteal PAD in patients who undergo BTK interventions can affect the outcome of the procedure. This report explores immediate procedural success and major adverse limb events at 1 year after balloon angioplasty treatment for isolated BTK PAD and in patients who underwent an additional femoropopliteal PAD intervention.

Vasoactive intestinal peptide exerts an osteoinductive effect in human mesenchymal stem cells.

Several neuropeptides present in bone tissues, produced by nerve fibers and bone cells, have been reported to play a role in regulating the fine-tuning of osteoblast and osteoclast functions to maintain bone homeostasis. This study aims to characterize the influence of the neuropeptide vasoactive intestinal peptide (VIP) on the differentiation process of human mesenchymal stem cells (MSCs) into osteoblasts and on their anabolic function. We describe the mRNA and protein expression profile of VIP and its receptors in MSCs as they differentiate into osteoblasts, suggesting the presence of an autocrine signaling pathway in these cells. Our findings reveal that VIP enhances the expression of early osteoblast markers in MSCs under osteogenic differentiation and favors both bone matrix formation and proper cytoskeletal reorganization. Finally, our data suggest that VIP could be exerting a direct modulatory role on the osteoblast to osteoclast signaling by downregulating the receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio. These results highlight the potential of VIP as an osteoinductive differentiation factor, emerging as a key molecule in the maintenance of human bone homeostasis.

A Survey of Self-Supervised and Few-Shot Object Detection.

Labeling data is often expensive and time-consuming, especially for tasks such as object detection and instance segmentation, which require dense labeling of the image. While few-shot object detection is about training a model on novel (unseen) object classes with little data, it still requires prior training on many labeled examples of base (seen) classes. On the other hand, self-supervised methods aim at learning representations from unlabeled data which transfer well to downstream tasks such as object detection. Combining few-shot and self-supervised object detection is a promising research direction. In this survey, we review and characterize the most recent approaches on few-shot and self-supervised object detection. Then, we give our main takeaways and discuss future research directions. Project page: https://gabrielhuang.github.io/fsod-survey/.

The Role of the Vagus Nerve in the Microbiome and Digestive System in Relation to Epilepsy.

The Enteric Nervous System (ENS) is described as a division of the Peripheral Nervous System (PNS), located within the gut wall and it is formed by two main plexuses: the myenteric plexus (Auerbach's) and the submucosal plexus (Meissner's). The contribution of the ENS to the pathophysiology of various neurological diseases such as Parkinson's or Alzheimer's disease has been described in the literature, while some other studies have found a connection between epilepsy and the gastrointestinal tract. The above could be explained by cholinergic neurons and neurotransmission systems in the myenteric and submucosal plexuses, regulating the vagal excitability effect. It is also understandable, as the discharges arising in the amygdala are transmitted to the intestine through projections the dorsal motor nucleus of the vagus, giving rise to efferent fibers that stimulate the gastrointestinal tract and consequently the symptoms at this level. Therefore, this review's main objective is to argue in favor of the existing relationship of the ENS with the Central Nervous System (CNS) as a facilitator of epileptogenic or ictogenic mechanisms. The gut microbiota also participates in this interaction; however, it depends on many individual factors of each human being. The link between the ENS and the CNS is a poorly studied epileptogenic site with a big impact on one of the most prevalent neurological conditions such as epilepsy.

Reproducibility of Femoropopliteal Artery Intravascular Ultrasound Imaging in Patients With Peripheral Artery Disease.

Despite increased use of intravascular ultrasound (IVUS) during peripheral artery interventions, evidence for reproducibility of IVUS measurements and its relation to angiography is lacking. Forty cross-sectional IVUS images of the femoropopliteal artery from 20 randomly selected patients enrolled in the XLPAD (Excellence in Peripheral Artery Disease) registry who underwent peripheral artery interventions and met criteria based on IVUS consensus guidelines were independently assessed by 2 blinded readers. IVUS images from 6 patients (40 images) were selected for angiographic correlation and met criteria for identifiable landmarks (e.g., stent edge and bifurcation). Lumen cross-sectional area (CSA), external elastic membrane (EEM) CSA, luminal diameter, and reference vessel diameter were repeatedly measured. The Lumen CSA and EEM CSA intra-observer agreement by Spearman rank-order correlation (ρ) was >0.993, intraclass correlation coefficient was >0.997, and repeatability coefficient was <1.34. For the interobserver measurement of luminal CSA and EEM CSA, the ρ = 0.742 and 0.764; intraclass correlation coefficient = 0.888 and 0.885; and repeatability coefficient = 7.24 and 11.34, respectively. A Bland-Altman plot for lumen and EEM CSA showed good reproducibility. For angiographic comparison, the ρ for luminal diameter, luminal area, and vessel area were 0.419, 0.414, and 0.649, respectively. Femoropopliteal IVUS measurements showed strong intra-observer and interobserver agreement; IVUS and angiographic measurements did not demonstrate a similar strong agreement.