Pharmacological blocking of spinal GABA receptors in monkeys reduces sensory transmission to the spinal cord, thalamus, and cortex.

A century of research established that GABA inhibits proprioceptive inputs presynaptically to sculpt spinal neural inputs into skilled motor output. Recent results in mice challenged this theory by showing that GABA can also facilitate action potential conduction in proprioceptive afferents. Here, we tackle this controversy in monkeys, the most human-relevant animal model, and show that GABA receptors (GABARs) indeed facilitate sensory inputs to spinal motoneurons and interneurons and that this mechanism also influences sensory transmission to supraspinal centers.

Bills to Restrict Access to and Harm From Indoor Tanning Facilities in US State Legislatures, 1992‒2023.

To describe progression, content, and stringency of state legislation regulating indoor tanning and association with state government political party leadership. Trained research assistants used legal mapping methods to code legislative bills on indoor tanning introduced in US states, the District of Columbia, and Puerto Rico. We calculated composite scores on the stringency of age restrictions and of warnings, operator requirements, and enforcement.

Distinct molecular profiles and shared drug vulnerabilities in pancreatic metastases of renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC) is the most common origin of pancreatic metastases (PM). Distinct genomic aberrations, favorable prognosis, and clinical observations on high angiogenesis, and succeeding tyrosine kinase inhibitor (TKI) sensitivity have been reported in PM-ccRCC. However, no functional or single-cell studies have been conducted thus far.

Venetoclax triggers sublethal apoptotic signaling in venetoclax-resistant acute myeloid leukemia cells and induces vulnerability to PARP inhibition and azacitidine.

Venetoclax plus azacitidine treatment is clinically beneficial for elderly and unfit acute myeloid leukemia (AML) patients. However, the treatment is rarely curative, and relapse due to resistant disease eventually emerges. Since no current clinically feasible treatments are known to be effective at the state of acquired venetoclax resistance, this is becoming a major challenge in AML treatment.

Supercomputer framework for reverse engineering firing patterns of neuron populations to identify their synaptic inputs.

In this study, we develop new reverse engineering (RE) techniques to identify the organization of the synaptic inputs generating firing patterns of populations of neurons. We tested these techniques in silico to allow rigorous evaluation of their effectiveness, using remarkably extensive parameter searches enabled by massively-parallel computation on supercomputers. We chose spinal motoneurons as our target neural system, since motoneurons process all motor commands and have well-established input-output properties.

Barriers and facilitators to skin cancer prevention among Hispanics: a qualitative study.

Background: In the past two decades, melanoma incidence among Hispanic people has risen greatly. This qualitative study explored Hispanic people's perceived barriers and facilitators to skin cancer-related preventive behaviors.

Methods: Five focus groups among Hispanic people (2 in Spanish and 3 in English; n = 34; 11 Spanish-preferring and 23 English-preferring) were conducted, where participants discussed their perceptions and behaviors relating to skin cancer, sun protection, and skin self-examination.

Ex Vivo Venetoclax Sensitivity Predicts Clinical Response in Acute Myeloid Leukemia in the Prospective VenEx Trial.

The BCL2 inhibitor venetoclax has shown promise for treating acute myeloid leukemia (AML). However, identifying patients likely to respond remains a challenge, especially for those with relapsed/refractory (R/R) disease. We evaluated the utility of ex vivo venetoclax sensitivity testing to predict treatment responses to venetoclax-azacitidine in a prospective, multicenter, phase 2 trial conducted by the Finnish AML Group (VenEx, NCT04267081).

Comparing emergency department versus high school-based recruitment for a hypertension research study with adult-youth dyads.

Dyads can be challenging to recruit for research studies, but detailed reporting on strategies employed to recruit adult-adolescent dyads is rare. We describe experiences recruiting adult-youth dyads for a hypertension education intervention comparing recruitment in an emergency department (ED) setting with a school-based community setting. We found more success in recruiting dyads through a school-based model that started with adolescent youth (19 dyads in 7 weeks with < 1 hour recruitment) compared to an ED-based model that started with adults (2 dyads in 17 weeks with 350 hours of recruitment).

Developing a Youth-Led Digital Hypertension Education Intervention for Adults With Hypertension: Qualitative Study on Refinement and Acceptability.

Background: Hypertension affects one-third of adults in the United States and is the leading risk factor for death. Underserved populations are seen disproportionately in the emergency department (ED) and tend to have worse blood pressure (BP) control. For adults, a lack of hypertension knowledge is a common barrier to hypertension control, while social support is a strong facilitator, and providing information that is culturally sensitive and relevant is especially important in this context.

Persistent inward currents in human motoneurons: emerging evidence and future directions.

The manner in which motoneurons respond to excitatory and inhibitory inputs depends strongly on how their intrinsic properties are influenced by the neuromodulators serotonin and noradrenaline. These neuromodulators enhance the activation of voltage-gated channels that generate persistent (long-lasting) inward sodium and calcium currents (PICs) into the motoneurons. PICs are crucial for initiating, accelerating, and maintaining motoneuron firing.

Voluntary co-contraction of ankle muscles alters motor unit discharge characteristics and reduces estimates of persistent inward currents.

Motoneuronal persistent inward currents (PICs) are facilitated by neuromodulatory inputs but are highly sensitive to local inhibitory circuits. Estimates of PICs are reduced by group Ia reciprocal inhibition, and increased with the diffuse actions of neuromodulators released during remote muscle contraction. However, it remains unknown how motoneurons function in the presence of simultaneous excitatory and inhibitory commands.

Interference with glutamate antiporter system x enables post-hypoxic long-term potentiation in hippocampus.

Our group previously showed that genetic or pharmacological inhibition of the cystine/glutamate antiporter, system x , mitigates excitotoxicity after anoxia by increasing latency to anoxic depolarization, thus attenuating the ischaemic core. Hypoxia, however, which prevails in the ischaemic penumbra, is a condition where neurotransmission is altered, but excitotoxicity is not triggered. The present study employed mild hypoxia to further probe ischaemia-induced changes in neuronal responsiveness from wild-type and xCT KO (xCT) mice.

Candidate proteins interacting with cytoskeleton in cells from the basal airway epithelium .

The cytoskeleton consists of actin, microtubules, septins, and intermediate filaments and, in most cells, is anchored to an extracellular matrix. Each cell has a unique arrangement of this network and readjusts it from time to time. To investigate the regulation of these reorganizations, we identified interactors from extracts of four cultured lines representing basal cells from the airway epithelium.

Associations of Social Factors and Self-Efficacy with Skin-Self Examination Intentions Among Hispanics at Risk for Skin Cancer and Their Preferences for Digital Interventions.

Skin cancer ranks as the most prevalent cancer in the United States. Over the past two decades, the incidence of melanoma, the deadliest form of skin cancer, among Hispanics has risen by 20%. Melanoma mortality rates are higher in Hispanics than in non-Hispanic Whites (NHW).

Digital Interventions to Modify Skin Cancer Risk Behaviors in a National Sample of Young Adults: Randomized Controlled Trial.

Background: Young adults engage in behaviors that place them at risk for skin cancer. Dissemination of digital health promotion interventions via social media is a potentially promising strategy to modify skin cancer risk behaviors by increasing UV radiation (UVR) protection and skin cancer examinations.

Objective: This study aimed to compare 3 digital interventions designed to modify UVR exposure, sun protection, and skin cancer detection behaviors among young adults at moderate to high risk of skin cancer.

A NEW POSTURAL MOTOR RESPONSE TO SPINAL CORD STIMULATION: POST-STIMULATION REBOUND EXTENSION.

Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring locomotion, little attention is paid to enabling standing which is a prerequisite of walking. In this study, we fully characterize a new type of response to SCS, a long extension activated post-stimulation (LEAP).

Piston-based specimen holder for rapid surgical and biopsy specimen imaging.

Advanced fluorescence imaging modalities such as confocal microscopy and two photon fluorescence microscopy can provide rapid, real-time histology images, but the mounting of fresh tissue specimens in standard orientations required for diagnosis without embedding and sectioning remains an unsolved problem. Here, we introduce a piston-based specimen holder designed for consistent, even pressure distribution. We improve upon previous designs by incorporating an air piston system with a flexible membrane and wick that extracts fluid during compression.

Neural dynamics of robust legged robots.

Legged robot control has improved in recent years with the rise of deep reinforcement learning, however, much of the underlying neural mechanisms remain difficult to interpret. Our aim is to leverage bio-inspired methods from computational neuroscience to better understand the neural activity of robust robot locomotion controllers. Similar to past work, we observe that terrain-based curriculum learning improves agent stability.

Targeting CD33+ Acute Myeloid Leukemia with GLK-33, a Lintuzumab-Auristatin Conjugate with a Wide Therapeutic Window.

CD33 (Siglec-3) is a cell surface receptor expressed in approximately 90% of acute myeloid leukemia (AML) blasts, making it an attractive target for therapy of AML. Although previous CD33-targeting antibody-drug conjugates (ADC) like gemtuzumab ozogamicin (GO, Mylotarg) have shown efficacy in AML treatment, they have suffered from toxicity and narrow therapeutic window. This study aimed to develop a novelADCwith improved tolerability and a wider therapeutic window.

Linkages between maternal experience of intimate partner violence and child nutrition outcomes: A rapid evidence assessment.

Background: A strong evidence base indicates that maternal caregivers' experience of intimate partner violence [IPV] impacts children's health, cognitive development, and risk-taking behaviors. Our objective was to review peer-reviewed literature describing the associations between a child's indirect exposure to IPV and corresponding nutrition outcomes, with a particular focus on fragile settings in low and middle-income countries [LMICs].

Methods: We conducted a rapid evidence assessment to synthesize quantitative associations between maternal caregivers' IPV experience and children's nutrition/growth outcomes (birthweight, feeding, and growth indicators).

Measurement of cigarette relighting: A common but understudied behavior.

Objective: Relighting, i.e., extinguishing, saving, and later relighting and smoking unfinished cigarettes, appears prevalent, may be associated with nicotine dependence and negative health outcomes, yet is poorly understood.