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Stereolithography enables the fabrication of three-dimensional (3D) freeform structures via light-induced polymerization. However, the accumulation of ultraviolet dose within resin trapped in negative spaces, such as microfluidic channels or voids, can result in the unintended closing, referred to as overcuring, of these negative spaces. We report the use of injection continuous liquid interface production to continuously displace resin at risk of overcuring in negative spaces created in previous layers with fresh resin to mitigate the loss of Z-axis resolution. We demonstrate the ability to resolve 50-µm microchannels, breaking the historical relationship between resin properties and negative space resolution. With this approach, we fabricated proof-of-concept 3D free-form microfluidic devices with improved design freedom over device material selection and resulting properties.

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Introduction: Human papillomavirus (HPV) testing as a method of cervical cancer screening can be performed by healthcare providers or by patients through self-sampling directly in the community, removing several barriers experienced by under screened populations. The objective of this scoping review was to determine which HPV self-sampling implementation and engagement strategies have been used to engage under screened populations (i.e., Indigenous, newcomer, and rural and remote communities) in cervical cancer screening. Methods: A scoping review was conducted searching MEDLINE, CINAHL, EMBASE, Cochrane Library, and SocINDEX from inception to August 2023. The inclusion criteria were: (1) Indigenous, newcomer, and rural and remote communities; (2) countries identified as members of the Organization for Economic Co-operation and Development; and (3) intervention included HPV self-sampling. The review was registered prior to conducting the search (https://osf.io/zfvp9). Results: A total of 26 studies out of 2,741 studies met the inclusion criteria. In-person engagement with trusted community leaders was the most widely used and accepted recruitment and engagement strategy across all three populations. Six out of seven studies with Indigenous communities distributed HPV self-sampling kits to eligible participants in person in a clinical setting for collection on site or at home. Similarly, nine of the identified studies that engaged newcomers recruited participants in person through the community, where eligible participants were either given a kit (n = 7) or received one in the mail (n = 2). Lastly, of the 10 identified studies engaging rural and remote participants in HPV self-sampling, six recruited eligible participants in person at various community locations and four used electronic medical records or registries to identify and mail kits to participants. Discussion: HPV self-sampling through in person kit distribution and mail out of HPV self-sampling kits is an effective way to increase participation rates amongst under screened populations.

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Detección Precoz del Cáncer , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Femenino , Detección Precoz del Cáncer/métodos , Infecciones por Papillomavirus/diagnóstico , Manejo de Especímenes/métodos , Tamizaje Masivo/métodos , Papillomaviridae/aislamiento & purificación , Adulto

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BACKGROUND: Although high-risk older patients benefit from a multidisciplinary approach to perioperative care, the specific roles and responsibilities of the clinicians involved have yet to be adequately characterized. METHODS: Qualitative analysis of semi-structured interviews with four anesthesia preoperative clinic providers, seven surgeons, and nine primary care providers in northern New England. RESULTS: The analysis revealed both distinct and overlapping roles and responsibilities. Anesthesia providers were described as a "safety net" and surgeons as "captain of the ship", in charge of getting "all the ducks in a row" to avoid surgery delays and cancellations. Primary care providers saw themselves as the "quarterback", ensuring care continuity and consideration of patient psychosocial factors. CONCLUSIONS: While all have a shared responsibility for facilitating patient-centered decision-making and a safe perioperative course, each discipline has different areas of focus and expertise. Role clarification can help optimize the distribution of responsibilities and enhance perioperative communication and collaboration.

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We present cryogenic ion vibrational spectroscopy of complexes of the anion receptor octamethyl calix[4]pyrrole (omC4P) with nitrate in vacuo. We compare the resulting vibrational spectrum with that in deuterated acetonitrile solution, and we interpret the results using density functional theory. Nitrate binds to omC4P through hydrogen bonds between the four NH groups of the receptor and a single NO group of the nitrate ion. The shape of the ion breaks the C4v symmetry of the receptor, and this symmetry lowering is encoded in the pattern of the NH stretching modes of omC4P. We compare the spectrum of nitrate-omC4P with that of chloride-omC4P to discuss effects of ion size, shape, and solvent interaction on the ion binding behavior.

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Using high-resolution 3D printing, a novel class of microneedle array patches (MAPs) is introduced, called latticed MAPs (L-MAPs). Unlike most MAPs which are composed of either solid structures or hollow needles, L-MAPs incorporate tapered struts that form hollow cells capable of trapping liquid droplets. The lattice structures can also be coated with traditional viscous coating formulations, enabling both liquid- and solid-state cargo delivery, on a single patch. Here, a library of 43 L-MAP designs is generated and in-silico modeling is used to down-select optimal geometries for further characterization. Compared to traditionally molded and solid-coated MAPs, L-MAPs can load more cargo with fewer needles per patch, enhancing cargo loading and drug delivery capabilities. Further, L-MAP cargo release kinetics into the skin can be tuned based on formulation and needle geometry. In this work, the utility of L-MAPs as a platform is demonstrated for the delivery of small molecules, mRNA lipid nanoparticles, and solid-state ovalbumin protein. In addition, the production of programmable L-MAPs is demonstrated with tunable cargo release profiles, enabled by combining needle geometries on a single patch.

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Substance use disorders are defined by persistent drug consumption despite adverse consequences. Accordingly, we developed two fentanyl-vs-shock avoidance/escape choice procedures in which male and female rats responded under a fixed-ratio (FR)1:FR1 concurrent schedule of shock avoidance/escape and IV fentanyl under either mutually exclusive or non-exclusive choice conditions. Initial experiments using a discrete-trial procedure determined behavioral allocation between mutually exclusive shock avoidance/escape and different fentanyl doses (0.32-18 µg/kg/infusion; Experiment 1). Shock intensity (0.1-0.7 mA) and shock avoidance/escape response requirement (FR1-16) were also manipulated (Experiment 2). Next, we used a free-operant procedure in which shock avoidance/escape and fentanyl were continuously available under non-exclusive conditions, and response-shock (R-S) interval (30-1000 s) was manipulated (Experiment 3). Finally, we tested the hypothesis that extended-access fentanyl self-administration would produce fentanyl dependence, establish fentanyl withdrawal as an endogenous negative reinforcer, and increase fentanyl choice in both procedures (Experiments 4 and 5). The shock avoidance/escape contingency decreased fentanyl self-administration, and rats consistently chose shock avoidance/escape over fentanyl in both choice conditions. Decreasing shock intensity or increasing shock avoidance/escape response requirement failed to increase fentanyl choice, suggesting that fentanyl and shock avoidance/escape are independent economic commodities. Increasing the R-S interval increased fentanyl choice but failed to increase shock delivery. Extended fentanyl access engendered high fentanyl intake and opioid withdrawal signs but failed to increase fentanyl choice under either choice condition. These results suggest that neither positive fentanyl reinforcement nor negative reinforcement by fentanyl withdrawal is sufficient to reduce shock avoidance/escape-maintained responding and increase foot shock as an adverse consequence.

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[This corrects the article DOI: 10.3389/fmolb.2023.1258333.].

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INTRODUCTION: To improve treatment access for emerging adults with cannabis use disorder (CUD), we developed a telehealth counseling-plus-mHealth intervention and remotely conducted a single-arm open pilot study to preliminarily evaluate its feasibility in primary care. METHODS: A multidisciplinary team including youth developed the intervention using the structure of the MOMENT intervention: two weekly counselor-delivered Motivational Enhancement Therapy (MET) sessions, then two weeks of smartphone surveys (4 prompted/day) querying socioemotional contexts and cannabis use, with pre-programmed messages on report of personal triggers for use (Ecological Momentary Intervention; EMI). The team adapted the MET for virtual delivery; created material to enhance self-reflection, plan behavior change, and anticipate withdrawal; shortened the sessions; and tested them with five youth actors. EMI messages were created to align with the MET and programmed to minimize repetition. Patients aged 18-25 using recreational cannabis ≥3 days/week were recruited from an urban medical practice. Participants received the intervention and responded to surveys on satisfaction and burden. At baseline, post-intervention, and two months, participants reported behavior change readiness/importance/confidence and cannabis use. EMI engagement was calculated as % days with ≥1 phone survey completed. RESULTS: Fourteen eligible patients enrolled; 79 % used cannabis daily/near-daily and 100 % reported use problems. All completed both MET sessions and responded to EMI surveys. All agreed/strongly agreed that they felt respected by, comfortable with, and trust for the counselor and that the activities and discussion were helpful; all rated the MET sessions as very good/excellent. Technical issues were infrequent and minor. Median EMI engagement was 100 % (≥1 report/day) in each week. Behavior change confidence was higher post-intervention and importance and confidence were higher at two months vs. baseline. By two months, 11 participants had started to change cannabis use; median percent days of use in the past 30 days declined by 27 % and average times of use per use day declined by 28 %. All rated intervention quality as good, very good, or excellent. CONCLUSIONS: Emerging adults were highly satisfied and engaged with a telehealth MET counseling-plus-mHealth EMI intervention for cannabis use and reported higher motivation to change cannabis use and less use post-intervention and at 2-month follow-up.

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Abuso de Marihuana , Telemedicina , Humanos , Proyectos Piloto , Masculino , Adulto Joven , Femenino , Adulto , Adolescente , Abuso de Marihuana/terapia , Consejo/métodos , Estudios de Factibilidad , Entrevista Motivacional/métodos

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Traumatic brain injury (TBI) is a leading cause of death and disability in pediatric patients and often results in delayed neural development and altered connectivity, leading to lifelong learning, memory, behavior, and motor function deficits. Induced pluripotent stem cell-derived neural stem cells (iNSCs) may serve as a novel multimodal therapeutic as iNSCs possess neuroprotective, regenerative, and cell-replacement capabilities post-TBI. In this study, we evaluated the effects of iNSC treatment on cellular, tissue, and functional recovery in a translational controlled cortical impact TBI piglet model. Five days post-craniectomy (n = 6) or TBI (n = 18), iNSCs (n = 7) or PBS (n = 11) were injected into perilesional brain tissue. Modified Rankin Scale (mRS) neurological evaluation, magnetic resonance imaging, and immunohistochemistry were performed over the 12-week study period. At 12-weeks post-transplantation, iNSCs showed long-term engraftment and differentiation into neurons, astrocytes, and oligodendrocytes. iNSC treatment enhanced endogenous neuroprotective and regenerative activities indicated by decreasing intracerebral immune responses, preserving endogenous neurons, and increasing neuroblast formation. These cellular changes corresponded with decreased hemispheric atrophy, midline shift, and lesion volume as well as the preservation of cerebral blood flow. iNSC treatment increased piglet survival and decreased mRS scores. The results of this study in a predictive pediatric large-animal pig model demonstrate that iNSC treatment is a robust multimodal therapeutic that has significant promise in potentially treating human pediatric TBI patients.

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Brain-machine interface (BMI) controlled functional electrical stimulation (FES) is a promising treatment to restore hand movements to people with cervical spinal cord injury. Recent intracortical BMIs have shown unprecedented successes in decoding user intentions, however the hand movements restored by FES have largely been limited to predetermined grasps. Restoring dexterous hand movements will require continuous control of many biomechanically linked degrees-of-freedom in the hand, such as wrist and finger flexion, that would form the basis of those movements. Here we investigate the ability to restore simultaneous wrist and finger flexion, which would enable grasping with a controlled hand posture and assist in manipulating objects once grasped. We demonstrate that intramuscular FES can enable monkeys with temporarily paralyzed hands to move their fingers and wrist across a functional range of motion, spanning an average 88.6 degrees at the metacarpophalangeal joint flexion and 71.3 degrees of wrist flexion, and intramuscular FES can control both joints simultaneously in a real-time task. Additionally, we demonstrate a monkey using an intracortical BMI to control the wrist and finger flexion in a virtual hand, both before and after the hand is temporarily paralyzed, even achieving success rates and acquisition times equivalent to able-bodied control with BMI control after temporary paralysis in two sessions. Together, this outlines a method using an artificial brain-to-body interface that could restore continuous wrist and finger movements after spinal cord injury.

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CelTOS is a malaria vaccine antigen that is conserved in Plasmodium and other apicomplexan parasites and plays a role in cell-traversal. The structural basis and mechanisms of CelTOS-induced protective immunity to parasites are unknown. Here, CelTOS-specific monoclonal antibodies (mAbs) 7g7 and 4h12 demonstrated multistage activity, protecting against liver infection and preventing parasite transmission to mosquitoes. Both mAbs demonstrated cross-species activity with sterile protection against in vivo challenge with transgenic parasites containing either P. falciparum or P. vivax CelTOS, and with transmission reducing activity against P. falciparum. The mAbs prevented CelTOS-mediated pore formation providing insight into the protective mechanisms. X-ray crystallography and mutant-library epitope mapping revealed two distinct broadly conserved neutralizing epitopes. 7g7 bound to a parallel dimer of CelTOS, while 4h12 bound to a novel antiparallel dimer architecture. These findings inform the design of antibody therapies and vaccines and raise the prospect of a single intervention to simultaneously combat P. falciparum and P. vivax malaria.

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Anticuerpos Monoclonales , Anticuerpos Antiprotozoarios , Vacunas contra la Malaria , Plasmodium falciparum , Plasmodium vivax , Anticuerpos Monoclonales/inmunología , Animales , Plasmodium falciparum/inmunología , Plasmodium vivax/inmunología , Vacunas contra la Malaria/inmunología , Anticuerpos Antiprotozoarios/inmunología , Ratones , Malaria Falciparum/inmunología , Malaria Falciparum/prevención & control , Malaria Falciparum/parasitología , Cristalografía por Rayos X , Epítopos/inmunología , Malaria Vivax/prevención & control , Malaria Vivax/inmunología , Malaria Vivax/parasitología , Antígenos de Protozoos/inmunología , Humanos , Femenino , Mapeo Epitopo , Malaria/inmunología , Malaria/prevención & control , Malaria/parasitología , Ratones Endogámicos BALB C , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/química

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BACKGROUND: Brain magnetic resonance imaging (MRI) is a crucial tool for clinical evaluation of the brain and neuroscience research. Obtaining successful non-sedated MRI in children who live in resource-limited settings may be an additional challenge. OBJECTIVE: To present a feasibility study of a novel, low-cost MRI training protocol used in a clinical research study in a rural/semi-rural region of Colombia and to examine neurodevelopmental factors associated with successful scans. MATERIALS AND METHODS: Fifty-seven typically developing Colombian children underwent a training protocol and non-sedated brain MRI at age 7. Group training utilized a customized booklet, an MRI toy set, and a simple mock scanner. Children attended MRI visits in small groups of two to three. Resting-state functional and structural images were acquired on a 1.5-Tesla scanner with a protocol duration of 30-40 minutes. MRI success was defined as the completion of all sequences and no more than mild motion artifact. Associations between the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Movement Assessment Battery for Children (MABC), Behavioral Rating Inventory of Executive Function (BRIEF), Child Behavior Checklist (CBCL), and Adaptive Behavior Assessment System (ABAS) scores and MRI success were analyzed. RESULTS: Mean (SD) age at first MRI attempt was 7.2 (0.2) years (median 7.2 years, interquartile range 7.1-7.3 years). Twenty-six (45.6%) participants were male. Fifty-one (89.5%) children were successful across two attempts; 44 (77.2%) were successful on their first attempt. Six (10.5%) were unsuccessful due to refusal or excessive motion. Age, sex, and scores across all neurodevelopmental assessments (MABC, TVIP, ABAS, BRIEF, CBCL, NIH Toolbox Flanker, NIH Toolbox Pattern Comparison, WPPSI) were not associated with likelihood of MRI success (P=0.18, 0.19, 0.38, 0.92, 0.84, 0.80, 1.00, 0.16, 0.75, 0.86, respectively). CONCLUSION: This cohort of children from a rural/semi-rural region of Colombia demonstrated comparable MRI success rates to other published cohorts after completing a low-cost MRI familiarization training protocol suitable for low-resource settings. Achieving non-sedated MRI success in children in low-resource and international settings is important for the continuing diversification of pediatric research studies.

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Estudios de Factibilidad , Imagen por Resonancia Magnética , Población Rural , Humanos , Colombia , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Niño , Encéfalo/diagnóstico por imagen

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The ultrafast dynamics of neutral copper oxide clusters (CunOx, n < 5) are reported using femtosecond pump probe spectroscopy in the gas phase. The transient spectra recorded for each cluster demonstrate they relax on a 100s of fs timescale followed by a long-lived (>50 ps) response. Density functional theory calculations are performed to determine the lowest energy structures and spin states. Topological descripters for the excited states are calculated (time-dependent density functional theory) to relate the measured excited state dynamics to changes in the cluster's electronic structure with increasing oxidation. Strong field ionization is demonstrated here to be a soft form of ionization and able to record transient signals for clusters previously determined to be unstable to nanosecond multiphoton ionization. The relative cluster stability is further demonstrated by signal enhancement/depreciation that is recorded through the synergy from the two laser pulses. Once the oxygen atoms exceed the number of copper atoms, a weakly bound superoxide O2 unit forms, exhibiting a higher spin state. All clusters that are not in the lowest spin configuration demonstrate fragmentation.

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Traumatic brain injury (TBI), a significant global health issue, is affecting ∼69 million annually. To better understand TBI's impact on brain function and assess the efficacy of treatments, this study uses a novel temporal-spatial cross-group approach with a porcine model, integrating resting-state functional magnetic resonance imaging (rs-fMRI) for temporal and arterial spin labeling for spatial information. Our research used 18 four-week-old pigs divided into three groups: TBI treated with saline (SLN, n = 6), TBI treated with fecal microbial transplant (FMT, n = 6), and a sham group (sham, n = 6) with only craniectomy surgery as the baseline. By applying machine learning techniques-specifically, independent component analysis and sparse dictionary learning-across seven identified resting-state networks, we assessed the temporal and spatial correlations indicative of treatment efficacy. Both temporal and spatial analyses revealed a consistent increase of correlation between the FMT and sham groups in the executive control and salience networks. Our results are further evidenced by a simulation study designed to mimic the progression of TBI severity through the introduction of variable Gaussian noise to an independent rs-fMRI dataset. The results demonstrate a decreasing temporal correlation between the sham and TBI groups with increasing injury severity, consistent with the experimental results. This study underscores the effectiveness of the methodology in evaluating post-TBI treatments such as the FMT. By presenting comprehensive experimental and simulated data, our research contributes significantly to the field and opens new paths for future investigations into TBI treatment evaluations.

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OBJECTIVE: Our study aims to examine the role of multi-disciplinary surgical pause committees (MDSPC) in perioperative planning to reduce adverse postoperative events and mortality rates. SUMMARY BACKGROUND DATA: Frail patients could benefit from preoperative MDSPCs when utilizing risk-benefit ratios for the proposed surgical plan. We examined whether MDSPCs improved clinical outcomes by developing individualized care plans and stratifying patients based on their level of frailty and ability to overcome external stressors. METHODS: We retrospectively collected patient information after MDSPC evaluation, at our medical center for 12 years since 2011. Patient's frailty risk assessment index (RAI) scores were calculated, and survival status was updated. MDSPCs plans were put into the following categories: proceed with the planned surgery (G1), proceed after medical optimization (G2), reduce invasiveness of surgery or anesthesia plan (G3), or adopt a non-surgical approach (G4). Chi-square and independent t-tests were used for categorical and numerical data, respectively. Survival analysis for 30-day (primary endpoint), one-year, and overall mortality rates used Kaplan-Meier. The alpha was set at 0.05. RESULTS: Clinical information was accessed from 12 women and 382 men. The average age was 71±11 years. 87.3% of planned surgical operations were stratified as ASA class III and IV. RAI scores were 36.4±9.6 (G1), similar to 37.4±10.8 (G2) but lower than 41.4±9.3 (G3) and 44.2±9.7 (G4) (P<0.001). Average survival duration was 35 months (G1), 35 months (G2), both significantly longer than 20 months (G3) and 18 months (G4) (P<0.001). CONCLUSION: Medical optimization improved overall survival and reduced death within 30 days and one year to be comparable to G1. Additionally, reducing the surgical invasiveness only improved survival advantage for six months, after which it was comparable to those in G4 with the worst outcome. RAI scoring is an excellent tool to predict the outcome of surgery, and it was used successfully in critically ill patients.

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In recent years, our view of coastal ecosystems has expanded and come into greater focus. We are currently making more types of observations over larger areas and at higher frequencies than ever before. These advances are timely, as coastal ecosystems are facing increasing pressures from climate change and anthropogenic stressors. This article synthesizes recent literature on emerging technologies for coastal ecosystem monitoring, including satellite monitoring, aerial and underwater drones, in situ sensor networks, fiber optic systems, and community science observatories. We also describe how advances in artificial intelligence and deep learning underpin all these technologies by enabling insights to be drawn from increasingly large data volumes. Even with these recent advances, there are still major gaps in coastal ecosystem monitoring that must be addressed to manage coastal ecosystems during a period of accelerating global change.

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The adult turtle spinal cord can generate multiple kinds of limb movements, including swimming, three forms of scratching, and limb withdrawal (flexion reflex), even without brain input and sensory feedback. There are many multifunctional spinal neurons, activated during multiple motor patterns, and some behaviorally specialized neurons, activated during only one. How do multifunctional and behaviorally specialized neurons each contribute to motor output? We analyzed in vivo intracellular recordings of multifunctional and specialized neurons. Neurons tended to spike in the same phase of the hip-flexor (HF) activity cycle during swimming and scratching, though one preferred opposite phases. During both swimming and scratching, a larger fraction of multifunctional neurons than specialized neurons were highly rhythmic. One group of multifunctional neurons was active during the HF-on phase and another during the HF-off phase. Thus, HF-extensor alternation may be generated by a subset of multifunctional spinal neurons during both swimming and scratching. Scratch-specialized neurons and flexion reflex-selective neurons may instead trigger their respective motor patterns, by biasing activity of multifunctional neurons. In phase-averaged membrane potentials of multifunctional neurons, trough phases were more highly correlated between swimming and scratching than peak phases, suggesting that rhythmic inhibition plays a greater role than rhythmic excitation. We also provide the first intracellular recording of a turtle swim-specialized neuron: tonically excited during swimming but inactive during scratching and flexion reflex. It displayed an excitatory postsynaptic potential following each swim-evoking electrical stimulus and thus may be an intermediary between reticulospinal axons and the swimming CPG they activate.

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Reflejo , Médula Espinal , Natación , Tortugas , Animales , Tortugas/fisiología , Natación/fisiología , Médula Espinal/fisiología , Reflejo/fisiología , Neuronas/fisiología , Potenciales de Acción/fisiología , Neuronas Motoras/fisiología

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A 44-year-old woman presented to the emergency department status post incidental discovery of a large lingual mass identified during workup of a known intracranial neoplasm. The patient presented with a 4-month history of progressive altered mental status, somnolence, aphasia, and dysphagia; symptomology was attributed to the suprasellar tumor. Metastatic disease to the oral cavity was the primary differential diagnosis. Imaging demonstrated a 5.5 × 5.5 cm posterior tongue mass with near complete pharynx obstruction. Prompt debulking and pathology workup occurred. On postoperative day 1, the patient experienced complete resolution of all symptoms. Given rapid improvement, neurological decline was ultimately attributed not to the suprasellar mass but instead as being secondary to profound obstructive sleep apnea and ensuing sleep deprivation caused by the lingual tumor. This case describes the rare finding of a massive lingual superficial angiomyxoma with a synchronous cerebral neoplasm in which the latter functioned as a diagnostic distraction.