Ketamine can produce oscillatory dynamics by engaging mechanisms dependent on the kinetics of NMDA receptors.

Ketamine is an NMDA-receptor antagonist that produces sedation, analgesia and dissociation at low doses and profound unconsciousness with antinociception at high doses. At high and low doses, ketamine can generate gamma oscillations (>25 Hz) in the electroencephalogram (EEG). The gamma oscillations are interrupted by slow-delta oscillations (0.1-4 Hz) at high doses. Ketamine's primary molecular targets and its oscillatory dynamics have been characterized. However, how the actions of ketamine at the subcellular level give rise to the oscillatory dynamics observed at the network level remains unknown. By developing a biophysical model of cortical circuits, we demonstrate how NMDA-receptor antagonism by ketamine can produce the oscillatory dynamics observed in human EEG recordings and non-human primate local field potential recordings. We have discovered how impaired NMDA-receptor kinetics can cause disinhibition in neuronal circuits and how a disinhibited interaction between NMDA-receptor-mediated excitation and GABA-receptor-mediated inhibition can produce gamma oscillations at high and low doses, and slow-delta oscillations at high doses. Our work uncovers general mechanisms for generating oscillatory brain dynamics that differs from ones previously reported, and provides important insights into ketamine's mechanisms of action as an anesthetic and as a therapy for treatment-resistant depression.

A Swine Burn Model for Investigating the Healing Process in Multiple Depth Burn Wounds.

Burn wound healing is a complex and long process. Despite extensive experience, plastic surgeons and specialized teams in burn centers still face significant challenges. Among these challenges, the extent of the burned soft tissue can evolve in the early phase, creating a delicate balance between conservative treatments and necrosing tissue removal. Thermal burns are the most common type, and burn depth varies depending on multiple parameters, such as temperature and exposure time. Burn depth also varies in time, and the secondary aggravation of the "shadow zone" remains a poorly understood phenomenon. In response to these challenges, several innovative treatments have been studied, and more are in the early development phase. Nanoparticles in modern wound dressings and artificial skin are examples of these modern therapies still under evaluation. Taken together, both burn diagnosis and burn treatments need substantial advancements, and research teams need a reliable and relevant model to test new tools and therapies. Among animal models, swine are the most relevant because of their strong similarities in skin structure with humans. More specifically, Yucatan minipigs show interesting features such as melanin pigmentation and slow growth, allowing for studying high phototypes and long-term healing. This article aims to describe a reliable and reproducible protocol to study multi-depth burn wounds in Yucatan minipigs, enabling long-term follow-up and providing a relevant model for diagnosis and therapeutic studies.

Tissue engineering strategies for breast reconstruction: a literature review of current advances and future directions.

Background and Objective: Mastectomy is a primary treatment for breast cancer patients, and both autologous and implant-based reconstructive techniques have shown excellent results. In recent years, advancements in bioengineering have led to a proliferation of innovative approaches to breast reconstruction. This article comprehensively explores the promising perspectives offered by bioengineering and tissue engineering in the field of breast reconstruction. Methods: A literature review was conducted between April and June 2023 on PubMed and Google Scholar Databases. All English and French articles related to bioengineering applied to the field of breast reconstruction were included. We used the Evidence-Based Veterinary Medicine Association (EBVM) Toolkit 14 checklist for narrative reviews as a quality assurance measure and the Scale for the Assessment of Narrative Review Articles (SANRA) tool to self-assess our methodology. Key Content and Findings: Over 130 references related to breast bioengineering were included. The analysis revealed four key applications: enhancing the quality of the skin envelope, improving the viability of fat grafting, creating breast shape and volume via bio-printing, and optimizing nipple reconstruction through engineering techniques. The primary identified approaches revolved around establishing structural support and enhancing cellular viability. Structural techniques predominantly involved the implementation of 3D printed, decellularized, or biocompatible material scaffolds. Meanwhile, promoting cellular content trophicity primarily focused on harnessing the regenerative potential of adipose-derived stem cells (ADSCs) and increasing the tissue's survivability and cell trophicity. Conclusions: Tissue and bioengineering hold immense promise in the field of breast reconstruction, offering a diverse array of approaches. By combining existing techniques with novel advancements, they have the potential to significantly enhance the therapeutic options available to plastic and reconstructive surgeons.

Multisensory gamma stimulation promotes glymphatic clearance of amyloid.

The glymphatic movement of fluid through the brain removes metabolic waste1-4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer's disease5-8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer's disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.

Rapid thalamocortical network switching mediated by cortical synchronization underlies propofol-induced EEG signatures: a biophysical model.

Propofol-mediated unconsciousness elicits strong alpha/low-beta and slow oscillations in the electroencephalogram (EEG) of patients. As anesthetic dose increases, the EEG signal changes in ways that give clues to the level of unconsciousness; the network mechanisms of these changes are only partially understood. Here, we construct a biophysical thalamocortical network involving brain stem influences that reproduces transitions in dynamics seen in the EEG involving the evolution of the power and frequency of alpha/low-beta and slow rhythm, as well as their interactions. Our model suggests that propofol engages thalamic spindle and cortical sleep mechanisms to elicit persistent alpha/low-beta and slow rhythms, respectively. The thalamocortical network fluctuates between two mutually exclusive states on the timescale of seconds. One state is characterized by continuous alpha/low-beta-frequency spiking in thalamus (C-state), whereas in the other, thalamic alpha spiking is interrupted by periods of co-occurring thalamic and cortical silence (I-state). In the I-state, alpha colocalizes to the peak of the slow oscillation; in the C-state, there is a variable relationship between an alpha/beta rhythm and the slow oscillation. The C-state predominates near loss of consciousness; with increasing dose, the proportion of time spent in the I-state increases, recapitulating EEG phenomenology. Cortical synchrony drives the switch to the I-state by changing the nature of the thalamocortical feedback. Brain stem influence on the strength of thalamocortical feedback mediates the amount of cortical synchrony. Our model implicates loss of low-beta, cortical synchrony, and coordinated thalamocortical silent periods as contributing to the unconscious state.NEW & NOTEWORTHY GABAergic anesthetics induce alpha/low-beta and slow oscillations in the EEG, which interact in dose-dependent ways. We constructed a thalamocortical model to investigate how these interdependent oscillations change with propofol dose. We find two dynamic states of thalamocortical coordination, which change on the timescale of seconds and dose-dependently mirror known changes in EEG. Thalamocortical feedback determines the oscillatory coupling and power seen in each state, and this is primarily driven by cortical synchrony and brain stem neuromodulation.

Basolateral amygdala oscillations enable fear learning in a biophysical model.

The basolateral amygdala (BLA) is a key site where fear learning takes place through synaptic plasticity. Rodent research shows prominent low theta (~3-6 Hz), high theta (~6-12 Hz), and gamma (>30 Hz) rhythms in the BLA local field potential recordings. However, it is not understood what role these rhythms play in supporting the plasticity. Here, we create a biophysically detailed model of the BLA circuit to show that several classes of interneurons (PV+, SOM+, and VIP+) in the BLA can be critically involved in producing the rhythms; these rhythms promote the formation of a dedicated fear circuit shaped through rhythmic gating of spike-timing-dependent plasticity. Each class of interneurons is necessary for the plasticity. We find that the low theta rhythm is a biomarker of successful fear conditioning. Finally, we discuss how the peptide released by the VIP+ cell may alter the dynamics of plasticity to support the necessary fine timing.

A Systematic Review of Pediatric Nonaccidental Burns: Protecting the Children Through Knowledge, Vigilance, and Prevention.

BACKGROUND: Inflicted burns on children are a particularly difficult medical and psychosocial issue. Pediatric nonaccidental burns (PNABs) are unfortunately relatively common. In our study, we aim to present the key findings on PNABs with the intention of raising awareness, improving early, and recognizing accurately by identifying red flags, developing triage tools, and establishing prevention strategies for this sensitive issue. METHODS: A computerized literature search was conducted on PubMed, Google Scholar, and Cochrane for articles published until November 2020. The online screening process was performed by 3 independent reviewers with the Covidence tool against set inclusion/exclusion criteria. The protocol was reported using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO). RESULTS: A total of 12 studies were included for analysis. Scald burns via forced immersion accounted for the majority of reported PNABs affecting both feet and hands. Complications included wound infection, sepsis, requiring systemic antibiotics, or intensive care. Abused children's parents had a history of mental illness, unemployment, substance abuse, incarceration, and/or low annual income. CONCLUSIONS: Scalds via forced immersion remain the most common mechanism of PNABs. All health care professionals must remain vigilant, be able to recognize subtle signs of abuse, triage patients appropriately, report to police and/or social services, and ensure no further harm is made to the child or children. Repeated abuse with burns can lead to death. Prevention and education are the cornerstones for addressing this social phenomenon.

Rapid synaptic and gamma rhythm signature of mouse critical period plasticity.

Early-life experience enduringly sculpts thalamocortical (TC) axons and sensory processing. Here, we identify the very first synaptic targets that initiate critical period plasticity, heralded by altered cortical oscillations. Monocular deprivation (MD) acutely induced a transient (<3 h) peak in EEG γ-power (~40 Hz) specifically within the visual cortex, but only when the critical period was open (juvenile mice or adults after dark-rearing, Lynx1-deletion, or diazepam-rescued GAD65-deficiency). Rapid TC input loss onto parvalbumin-expressing (PV) inhibitory interneurons (but not onto nearby pyramidal cells) was observed within hours of MD in a TC slice preserving the visual pathway - again once critical periods opened. Computational TC modeling of the emergent γ-rhythm in response to MD delineated a cortical interneuronal gamma (ING) rhythm in networks of PV-cells bearing gap junctions at the start of the critical period. The ING rhythm effectively dissociated thalamic input from cortical spiking, leading to rapid loss of previously strong TC-to-PV connections through standard spike-timing-dependent plasticity rules. As a consequence, previously silent TC-to-PV connections could strengthen on a slower timescale, capturing the gradually increasing γ-frequency and eventual fade-out over time. Thus, ING enables cortical dynamics to transition from being dominated by the strongest TC input to one that senses the statistics of population TC input after MD. Taken together, our findings reveal the initial synaptic events underlying critical period plasticity and suggest that the fleeting ING accompanying a brief sensory perturbation may serve as a robust readout of TC network state with which to probe developmental trajectories.

Induction of labor: reviewing the past to improve the future.

BACKGROUND: Women undergoing induction of labor should be empowered with accurate information. OBJECTIVE: This study aimed to examine the characteristics of and indications for induction of labor and delivery outcomes to help inform practice and counseling. STUDY DESIGN: We conducted a retrospective cohort study of all singleton pregnancies undergoing induction of labor over a 3-month period in a tertiary-level hospital in the Republic of Ireland. Data were obtained from paper and electronic registries. Descriptive and inferential statistics were performed on data collected. RESULTS: There were 1084 women delivered, with an induction rate of 46.0% (n=499). Primiparous women were more likely to be induced compared with multiparous women (51.4%; n=254/494 vs 41.5%; n=245/590; P<.001), and were more likely to be induced for postmaturity (30.7%; n=78/254 vs 23.6%; 58/245; P≤.001). More than half (50.3%; 251/399) were induced before 40 weeks' gestation, irrespective of parity. Multiparous women and those induced for maternal medical indications had a shorter overall time to delivery interval (21.7 hours [standard deviation, 13.0] vs 13.8 hours [standard deviation, 11.2]; P<.001 and 18.3 hours [standard deviation, 12.7] vs 14.7 hours [standard deviation, 12.4]; P<.01). CONCLUSION: Information on induction of labor can aid in the guidance and education of women undergoing the process, educate clinicians for appropriate counseling, and facilitate shared decision-making.

Deep brain stimulation in the subthalamic nucleus for Parkinson's disease can restore dynamics of striatal networks.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is highly effective in alleviating movement disability in patients with Parkinson's disease (PD). However, its therapeutic mechanism of action is unknown. The healthy striatum exhibits rich dynamics resulting from an interaction of beta, gamma, and theta oscillations. These rhythms are essential to selection and execution of motor programs, and their loss or exaggeration due to dopamine (DA) depletion in PD is a major source of behavioral deficits. Restoring the natural rhythms may then be instrumental in the therapeutic action of DBS. We develop a biophysical networked model of a BG pathway to study how abnormal beta oscillations can emerge throughout the BG in PD and how DBS can restore normal beta, gamma, and theta striatal rhythms. Our model incorporates STN projections to the striatum, long known but understudied, found to preferentially target fast-spiking interneurons (FSI). We find that DBS in STN can normalize striatal medium spiny neuron activity by recruiting FSI dynamics and restoring the inhibitory potency of FSIs observed in normal conditions. We also find that DBS allows the reexpression of gamma and theta rhythms, thought to be dependent on high DA levels and thus lost in PD, through cortical noise control. Our study highlights that DBS effects can go beyond regularizing BG output dynamics to restoring normal internal BG dynamics and the ability to regulate them. It also suggests how gamma and theta oscillations can be leveraged to supplement DBS treatment and enhance its effectiveness.

Adults with learning disabilities want loving relationships, but may need support.

The studyMcCarthy M, Bates C, Elson N, Hunt S, Milne-Skillman, Forrester-Jones R. 'Love makes me feel good inside and my heart is fixed': What adults with intellectual disabilities have to say about love and relationships. J Appl Res Intellect Disabil 2021;00:1-11.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/romantic-relationships-adults-with-learning-disabilities/.

'Love makes me feel good inside and my heart is fixed': What adults with intellectual disabilities have to say about love and relationships.

BACKGROUND: Adults with intellectual disabilities have historically been hindered, rather than supported, in their desire to form loving relationships. This paper sought to explore with them what kinds of support they wanted in the 21st Century. METHOD: Semi-structured in-depth interviews were conducted with 40 adults with intellectual disabilities in the United Kingdom. RESULTS: Participants placed a high value on having a partner and being supported to maintain and develop a loving relationship. The factors which constrained them in achieving this included a lack of social opportunities, barriers created by social care services and limits on them exercising autonomy. Facilitating factors included access to specialist dating agencies, strong family and staff support and opportunities to learn about relationships. CONCLUSIONS: The importance of a loving relationship as a source of pleasure and meaning in the lives of adults with intellectual disabilities who are often disadvantaged in many other spheres of life is emphasised.

Social networks and people with intellectual disabilities: A systematic review.

BACKGROUND: Despite the importance of social networks for health and well-being, relatively little is known about the ways in which adults with intellectual disabilities in the U.K. experience their social networks. METHOD: A systematic review was completed to identify research focused on the social networks of adults with intellectual disabilities. Studies published from 1990 to 2019 were identified. Studies were thematically analysed. RESULTS: Quantitative, qualitative and mixed methods studies were analysed to identify key factors influencing social networks. Experiences of people with intellectual disabilities identified themes of identity, powerlessness, inclusion, family and support. These themes are discussed with reference to theories of stigma and normalisation. CONCLUSIONS: Stigma and normalisation can be used to better understand the needs, desires and dreams of people with intellectual disabilities for ordinary relationships, from which they are regularly excluded. Implications for policy and practice are discussed in relation to building and repairing often spoiled identities.

Enhanced Recovery After Surgery Protocol With Ultrasound-Guided Regional Blocks in Outpatient Plastic Surgery Patients Leads to Decreased Opioid Prescriptions and Consumption.

BACKGROUND: Opioids are a mainstay of pain management. To limit the use of opioids, enhanced recovery after surgery (ERAS) protocols implement multimodal approaches to treat postoperative pain. OBJECTIVES: The aim of this paper was to be the first to assess the efficacy of an ERAS protocol for plastic surgery outpatients that includes ultrasound-guided, surgeon-led regional blocks. METHODS: A retrospective review of patients undergoing outpatient plastic surgery on an ERAS protocol was performed. These patients were compared to a well-matched group not on an ERAS protocol (pre-ERAS). Endpoints included the amounts of opioid, antinausea, and antispasmodic medication prescribed. ERAS patients were given a postoperative questionnaire to assess both pain levels (0-10) and opioid consumption. ERAS patients anticipated to have higher levels of pain received ultrasound-guided anesthetic blocks. RESULTS: There were 157 patients in the pre-ERAS group and 202 patients in the ERAS group. Patients in the pre-ERAS group were prescribed more opioid (332.3 vs 100.3 morphine milligram equivalents (MME)/patient; P < 0.001), antinausea (664 vs 16.3 mg of promethazine/patient; P < 0.001), and antispasmodic (401.3 vs 31.2 mg of cyclobenzaprine/patient; P < 0.001) medication. Patients on the ERAS protocol consumed an average total of 22.7 MME/patient postoperatively. Average pain scores in this group peaked at 5.32 on postoperative day 1 and then decreased significantly daily. CONCLUSIONS: Implementation of an ERAS protocol for plastic surgery outpatients with utilization of ultrasound-guided regional anesthetic blocks is feasible and efficacious. The ability to significantly decrease prescribed opioids in this unique patient population is noteworthy.

Risk of forced marriage amongst people with learning disabilities in the UK: Perspectives of South Asian carers.

BACKGROUND: People with intellectual disabilities are at increased risk of forced marriage compared to those without intellectual disabilities. In the UK, this risk is particularly, though not exclusively, associated with South Asian communities and is linked to the desire to secure long-term care. METHOD: Focus groups and semi-structured interviews were undertaken with South Asian parents and family carers (n = 22) of adults with intellectual disability and the resultant data thematically analysed. RESULTS: Although securing care for their intellectually disabled relative was identified as a key motivator for forced marriage, other important themes also emerged. These included cultural and religious beliefs about disability and marriage, and limited understanding of relevant laws. Factors militating against forced marriage were also identified, including fears of abuse and neglect. CONCLUSIONS: Implications for the provision of services and the need for improved access to information on forced marriage of people with intellectual disabilities are highlighted.

Human Adipose Derived Cells in Two- and Three-Dimensional Cultures: Functional Validation of an In Vitro Fat Construct.

Obesity, defined as a body mass index of 30 kg/m2 or above, has increased considerably in incidence and frequency within the United States and globally. Associated comorbidities including cardiovascular disease, type 2 diabetes mellitus, metabolic syndrome, and nonalcoholic fatty liver disease have led to a focus on the mechanisms promoting the prevention and treatment of obesity. Commonly utilized in vitro models employ human or mouse preadipocyte cell lines in a 2-dimensional (2D) format. Due to the structural, biochemical, and biological limitations of these models, increased attention has been placed on "organ on a chip" technologies for a 3-dimensional (3D) culture. Herein, we describe a method employing cryopreserved primary human stromal vascular fraction (SVF) cells and a human blood product-derived biological scaffold to create a 3D adipose depot in vitro. The "fat-on-chip" 3D cultures have been validated relative to 2D cultures based on proliferation, flow cytometry, adipogenic differentiation, confocal microscopy/immunofluorescence, and functional assays (adipokine secretion, glucose uptake, and lipolysis). Thus, the in vitro culture system demonstrates the critical characteristics required for a humanized 3D white adipose tissue (WAT) model.

Ultrasound Imaging of the Superficial Fascial System Can Predict the Subcutaneous Strength of Abdominal Tissue Using Mean Gray Value Quantification.

BACKGROUND: This study is the first to correlate sonographic findings of subcutaneous tissue to structural and biomechanical properties. METHODS: Precisely sized tissue specimens (59 samples) were collected from five abdominoplasty procedures. A Philips Lumify L12-4 linear array probe, connected to an Android tablet, was used to obtain ultrasound images of the superficial fascial system. A no. 1 Vicryl suture on a CTX needle placed though a needle guide within a three-dimensionally printed template ensured equal bites of subcutaneous tissue across specimens. Suture pull-out strength was measured until failure at a displacement rate of 2.12 mm/second using an Admet MTEST Quattro. Mean gray value for the superficial fascial system in associated ultrasonographic images was quantified by CellProfiler. RESULTS: Superficial fascial system visualization can be accomplished using high-resolution portable ultrasound. Comparing multiple specimens' imaging, interpatient and intrapatient variability of superficial fascial system quantity and structural characteristics are apparent. The superficial fascial system is highly abundant in some patients, but has limited presence in others. Individual-specimen mean gray value and whole-patient mean gray value positively correlated with tissue tensile strength (p = 0.006) and patient-average tissue tensile strength (p = 0.036), respectively. Whole-patient mean gray value accounted for 98.5 percent of the variance seen in patient-average tensile strength, making it a strong predictor for tensile strength. CONCLUSIONS: Portable ultrasound and image-processing technology can visualize, quantify, and predict subcutaneous tissue strength of the superficial fascial system. The superficial fascial system quantity correlates with suture tensile strength. Clinically, preoperative superficial fascial system quantification may aid in outcome predictions, manage patient expectations, and potentially lower complication rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, V.