Next-Generation Contraceptive Intravaginal Ring: Comparison of Etonogestrel and Ethinyl Estradiol In Vitro and In Vivo Release from 3D-Printed Intravaginal Ring and NuvaRing.

Intravaginal rings (IVRs) represent a well-established, woman-controlled and sustained vaginal drug delivery system suitable for a wide range of applications. Here, we sought to investigate the differences in etonogestrel (ENG) and ethinyl estradiol (EE) release from a 3D-printed IVR utilizing continuous liquid interface production (CLIP™) (referred to as CLIP for low drug loading and CLIP IVRs for high drug loading) and NuvaRing, a commercially available injection molded IVR. We conducted in vitro release studies in simulated vaginal fluid to compare the release of ENG and EE from CLIP IVRs and NuvaRing.

Discernible interindividual patterns of global efficiency decline during theoretical brain surgery.

The concept of functional localization within the brain and the associated risk of resecting these areas during removal of infiltrating tumors, such as diffuse gliomas, are well established in neurosurgery. Global efficiency (GE) is a graph theory concept that can be used to simulate connectome disruption following tumor resection. Structural connectivity graphs were created from diffusion tractography obtained from the brains of 80 healthy adults.

Functional connectivity in ADHD children doing Go/No-Go tasks: An fMRI systematic review and meta-analysis.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders diagnosed in childhood. Two common features of ADHD are impaired behavioural inhibition and sustained attention. The Go/No-Go experimental paradigm with concurrent functional magnetic resonance imaging (fMRI) scanning has previously revealed important neurobiological correlates of ADHD such as the supplementary motor area and the prefrontal cortex.

Identifying the Target Traumatic Brain Injury Population for Hyperbaric Oxygen Therapy.

Traumatic brain injury (TBI) results from direct penetrating and indirect non-penetrating forces that alters brain functions, affecting millions of individuals annually. Primary injury following TBI is exacerbated by secondary brain injury; foremost is the deleterious inflammatory response. One therapeutic intervention being increasingly explored for TBI is hyperbaric oxygen therapy (HBOT), which is already approved clinically for treating open wounds.

Parcellation-Based Connectivity Model of the Judgement Core.

Judgement is a higher-order brain function utilized in the evaluation process of problem solving. However, heterogeneity in the task methodology based on the many definitions of judgement and its expansive and nuanced applications have prevented the identification of a unified cortical model at a level of granularity necessary for clinical translation. Forty-six task-based fMRI studies were used to generate activation-likelihood estimations (ALE) across moral, social, risky, and interpersonal judgement paradigms.

Next generation 3D-printed intravaginal ring for prevention of HIV and unintended pregnancy.

Globally, there are 20 million adolescent girls and young women living with HIV who have limited access to long-acting, effective, women-controlled preventative methods. Additionally, although there are many contraceptive methods available, globally, half of all pregnancies remain unintended. Here we report the first 3D-printed multipurpose prevention technology (MPT) intravaginal ring (IVR) for HIV prevention and contraception.

Dose-Ranging Plasma and Genital Tissue Pharmacokinetics and Biodegradation of Ultra-Long-Acting Cabotegravir In Situ Forming Implant.

HIV continues to affect millions of men and women worldwide. The development of long-acting injectables for HIV prevention can overcome adherence challenges with daily oral prevention regimens by reducing dosing frequency and stigma. We previously developed an ultra-long-acting injectable, biodegradable, and removeable in situ forming implant (ISFI) with cabotegravir (CAB) that demonstrated protection after multiple rectal SHIV challenges in female macaques.

Functional connectivity of the language area in migraine: a preliminary classification model.

Background: Migraine is a complex disorder characterized by debilitating headaches. Despite its prevalence, its pathophysiology remains unknown, with subsequent gaps in diagnosis and treatment. We combined machine learning with connectivity analysis and applied a whole-brain network approach to identify potential targets for migraine diagnosis and treatment.

Functional connectivity reveals different brain networks underlying the idiopathic foreign accent syndrome.

Foreign accent syndrome (FAS) is characterized by new onset speech that is perceived as foreign. Available data from acquired cases suggests focal brain damage in language and sensorimotor brain networks, but little remains known about abnormal functional connectivity in idiopathic cases of FAS without structural damage. Here, connectomic analyses were completed on three patients with idiopathic FAS to investigate unique functional connectivity abnormalities underlying accent change for the first time.

Real world demonstration of hand motor mapping using the structural connectivity atlas.

Background: Locating the hand-motor-cortex (HMC) is an essential component within many neurosurgeries. Despite advancements in these localization methods there are still downfalls for each. Additionally, the importance of presurgical planning calls for increasingly accurate and efficient methods of locating specific cortical regions.

An agile, data-driven approach for target selection in rTMS therapy for anxiety symptoms: Proof of concept and preliminary data for two novel targets.

Introduction: Data-driven approaches to transcranial magnetic stimulation (TMS) might yield more consistent and symptom-specific results based on individualized functional connectivity analyses compared to previous traditional approaches due to more precise targeting. We provide a proof of concept for an agile target selection paradigm based on using connectomic methods that can be used to detect patient-specific abnormal functional connectivity, guide treatment aimed at the most abnormal regions, and optimize the rapid development of new hypotheses for future study.

Methods: We used the resting-state functional MRI data of 28 patients with medically refractory generalized anxiety disorder to perform agile target selection based on abnormal functional connectivity patterns between the Default Mode Network (DMN) and Central Executive Network (CEN).

Topology of the lateral visual system: The fundus of the superior temporal sulcus and parietal area H connect nonvisual cerebrum to the lateral occipital lobe.

Background And Purpose: Mapping the topology of the visual system is critical for understanding how complex cognitive processes like reading can occur. We aim to describe the connectivity of the visual system to understand how the cerebrum accesses visual information in the lateral occipital lobe.

Methods: Using meta-analytic software focused on task-based functional MRI studies, an activation likelihood estimation (ALE) of the visual network was created.

Symptom-circuit mappings of the schizophrenia connectome.

Objective: This paper aims to model the anatomical circuits underlying schizophrenia symptoms, and to explore patterns of abnormal connectivity among brain networks affected by psychopathology.

Methods: T1 magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), and resting-state functional MRI (rsfMRI) were obtained from a total of 126 patients with schizophrenia who were recruited for the study. The images were processed using the Omniscient software (https://www.

Connectomics underlying motor functional outcomes in the acute period following stroke.

Objective: Stroke remains the number one cause of morbidity in many developing countries, and while effective neurorehabilitation strategies exist, it remains difficult to predict the individual trajectories of patients in the acute period, making personalized therapies difficult. Sophisticated and data-driven methods are necessary to identify markers of functional outcomes.

Methods: Baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI (rsfMRI), and diffusion weighted scans were obtained from 79 patients following stroke.

Functional connectivity analysis of the depression connectome provides potential markers and targets for transcranial magnetic stimulation.

Background: Despite efforts to improve targeting accuracy of the dorsolateral prefrontal cortex (DLPFC) as a repetitive transcranial magnetic stimulation (rTMS) target for Major Depressive Disorder (MDD), the heterogeneity in clinical response remains unexplained.

Objective: We sought to compare the patterns of functional connectivity from the DLPFC treatment site in patients with MDD who were TMS responders to those who were TMS non-responders.

Methods: Baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI, and diffusion weighted imaging scans were obtained from 37 participants before they underwent a course of rTMS to left Brodmann area 46.

Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection.

Ultra-long-acting delivery platforms for HIV pre-exposure prophylaxis (PrEP) may increase adherence and maximize public health benefit. We report on an injectable, biodegradable, and removable in-situ forming implant (ISFI) that is administered subcutaneously and can release the integrase inhibitor cabotegravir (CAB) above protective benchmarks for more than 6 months. CAB ISFIs are well-tolerated in female mice and female macaques showing no signs of toxicity or chronic inflammation.

Delayed, Progressive Multivessel Occlusion After Resection of a Recurrent Glioma.

Glioblastoma multiforme (GBM) is one of the most common primary brain tumors with an aggressive natural history consistent with a median survival of less than two years. Most clinical research has primarily focused on improving overall survival through aggressive cytoreductive surgery and adjuvant radiochemotherapy. However, far less clinical guidance has been given for unexpected instances of neurologic decline following safe glioma resection in the setting of vascular etiology.

Graph Theory Measures and Their Application to Neurosurgical Eloquence.

Improving patient safety and preserving eloquent brain are crucial in neurosurgery. Since there is significant clinical variability in post-operative lesions suffered by patients who undergo surgery in the same areas deemed compensable, there is an unknown degree of inter-individual variability in brain 'eloquence'. Advances in connectomic mapping efforts through diffusion tractography allow for utilization of non-invasive imaging and statistical modeling to graphically represent the brain.

Use of machine learning to identify functional connectivity changes in a clinical cohort of patients at risk for dementia.

Objective: Progressive conditions characterized by cognitive decline, including mild cognitive impairment (MCI) and subjective cognitive decline (SCD) are clinical conditions representing a major risk factor to develop dementia, however, the diagnosis of these pre-dementia conditions remains a challenge given the heterogeneity in clinical trajectories. Earlier diagnosis requires data-driven approaches for improved and targeted treatment modalities.

Methods: Neuropsychological tests, baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI (rsfMRI), and diffusion weighted scans were obtained from 35 patients with SCD, 19 with MCI, and 36 age-matched healthy controls (HC).

Connectomic disturbances underlying insomnia disorder and predictors of treatment response.

Objective: Despite its prevalence, insomnia disorder (ID) remains poorly understood. In this study, we used machine learning to analyze the functional connectivity (FC) disturbances underlying ID, and identify potential predictors of treatment response through recurrent transcranial magnetic stimulation (rTMS) and pharmacotherapy.

Materials And Methods: 51 adult patients with chronic insomnia and 42 healthy age and education matched controls underwent baseline anatomical T1 magnetic resonance imaging (MRI), resting-stage functional MRI (rsfMRI), and diffusion weighted imaging (DWI).

Effects of Drug Physicochemical Properties on In-Situ Forming Implant Polymer Degradation and Drug Release Kinetics.

In-situ forming implants (ISFIs) represent a simple, tunable, and biodegradable polymer-based platform for long-acting drug delivery. However, drugs with different physicochemical properties and physical states in the polymer-solvent system exhibit different drug release kinetics. Although a few limited studies have been performed attempting to elucidate these effects, a large, systematic study has not been performed until now.

Parcellation-based tractographic modeling of the salience network through meta-analysis.

Background: The salience network (SN) is a transitory mediator between active and passive states of mind. Multiple cortical areas, including the opercular, insular, and cingulate cortices have been linked in this processing, though knowledge of network connectivity has been devoid of structural specificity.

Objective: The current study sought to create an anatomically specific connectivity model of the neural substrates involved in the salience network.