Distinct lateral hypothalamic CaMKIIα neuronal populations regulate wakefulness and locomotor activity.

For nearly a century, evidence has accumulated indicating that the lateral hypothalamus (LH) contains neurons essential to sustain wakefulness. While lesion or inactivation of LH neurons produces a profound increase in sleep, stimulation of inhibitory LH neurons promotes wakefulness. To date, the primary wake-promoting cells that have been identified in the LH are the hypocretin/orexin (Hcrt) neurons, yet these neurons have little impact on total sleep or wake duration across the 24-h period. Recently, we and others have identified other LH populations that increase wakefulness. In the present study, we conducted microendoscopic calcium imaging in the LH concomitant with EEG and locomotor activity (LMA) recordings and found that a subset of LH neurons that express Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) are preferentially active during wakefulness. Chemogenetic activation of these neurons induced sustained wakefulness and greatly increased LMA even in the absence of Hcrt signaling. Few LH CaMKIIα-expressing neurons are hypocretinergic or histaminergic while a small but significant proportion are GABAergic. Ablation of LH inhibitory neurons followed by activation of the remaining LH CaMKIIα neurons induced similar levels of wakefulness but blunted the LMA increase. Ablated animals showed no significant changes in sleep architecture but both spontaneous LMA and high theta (8 to 10 Hz) power during wakefulness were reduced. Together, these findings indicate the existence of two subpopulations of LH CaMKIIα neurons: an inhibitory population that promotes locomotion without affecting sleep architecture and an excitatory population that promotes prolonged wakefulness even in the absence of Hcrt signaling.

A Qualitative Study of the Pain Experience of Black Individuals With Cancer Taking Long-Acting Opioids.

BACKGROUND: Little is known about the experience of Black individuals with cancer taking long-acting opioids for cancer pain. OBJECTIVE: This study aimed to describe the day-to-day experience of living with pain and the experiences of taking opioids for pain management among Black individuals with cancer prescribed with long-acting opioids. METHODS: This qualitative descriptive study was part of a larger investigation focused on opioid adherence. Participants (N = 14) were interviewed using a semistructured interview guide. Analysis followed conventional content analysis and constant comparison approaches. Sociodemographics, clinical information, and the Brief Pain Inventory form were collected. RESULTS: The majority of the subsample was female (64.3%), not married (78.6%), and with a median age of 52.5 years. Participants were taking either MS Contin (85.7%) or OxyContin (14.3%). The Brief Pain Inventory median "average" pain severity scores and pain interference scores were 5.1/10 (interquartile range [IQR] = 6.1) and 3.5/10 (IQR = 6.7), respectively. Three themes are reported from the analyses: desire for control, barriers to pain relief, and isolation versus connectedness. CONCLUSION: Our findings highlight the persistent nature of moderate to severe cancer pain and how pain and its treatment interfere with patients' lives. The findings describe ways that patients learn to manage and exert control over pain despite conflicting attitudes and dealing with opioid stigma. IMPLICATION FOR PRACTICE: Clinicians should partner with patients with cancer, especially people of color, who may experience intersecting stigmas related to their cancer pain and opioid use, to best provide an individualized and culturally sensitive pain treatment plan.

Do intelligent leaders differentiate exchange relationships intelligently? A functional leadership approach to leader-member exchange differentiation.

The burgeoning literature on leader-member exchange (LMX) differentiation indicates that differentiating LMX relationships within groups has both benefits and costs when it comes to group effectiveness. Although some clarity is emerging surrounding the null total effect of LMX differentiation on group performance, we still know little about how leaders themselves shape the differentiation process. In this article, we extend theory to suggest that some leaders may differentiate more effectively than others. Drawing from functional leadership theory, we first identify a potential approach available to leaders likely to enhance their functional effectiveness-strategically investing in and developing stronger social exchange relationships with subordinates who can best help them fulfill the task functions (via task performance-based differentiation) and group maintenance functions (via contextual performance-based differentiation) specified within functional leadership theory. Embedding this potential approach within the ability-motivation-opportunity framework, we then develop a theory for which leaders are best positioned to recognize and pursue strategic relationship development this way. Specifically, we posit that leaders with stronger cognitive abilities (g) are more likely to recognize the value of such an approach, and those high in core self-evaluation are more likely to believe in their capabilities to successfully process, execute on, and persist with the approach. The results from two studies-a multisource study of leaders and team members in newly formed teams as well as a preregistered online vignette study using a sample of current and former supervisors-largely supported our predictions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

L-Type Calcium Channels Contribute to Ethanol-Induced Aberrant Tangential Migration of Primordial Cortical GABAergic Interneurons in the Embryonic Medial Prefrontal Cortex.

Exposure of the fetus to alcohol (ethanol) via maternal consumption during pregnancy can result in fetal alcohol spectrum disorders (FASD), hallmarked by long-term physical, behavioral, and intellectual abnormalities. In our preclinical mouse model of FASD, prenatal ethanol exposure disrupts tangential migration of corticopetal GABAergic interneurons (GINs) in the embryonic medial prefrontal cortex (mPFC). We postulated that ethanol perturbed the normal pattern of tangential migration via enhancing GABAA receptor-mediated membrane depolarization that prevails during embryonic development in GABAergic cortical interneurons. However, beyond this, our understanding of the underlying mechanisms is incomplete. Here, we tested the hypothesis that the ethanol-enhanced depolarization triggers downstream an increase in high-voltage-activated nifedipine-sensitive L-type calcium channel (LTCC) activity and provide evidence implicating calcium dynamics in the signaling scheme underlying the migration of embryonic GINs and its aberrance. Tangentially migrating Nkx2.1+ GINs expressed immunoreactivity to Cav1.2, the canonical neuronal isoform of the L-type calcium channel. Prenatal ethanol exposure did not alter its protein expression profile in the embryonic mPFC. However, exposing ethanol concomitantly with the LTCC blocker nifedipine prevented the ethanol-induced aberrant migration both in vitro and in vivo In addition, whole-cell patch clamp recording of LTCCs in GINs migrating in embryonic mPFC slices revealed that acutely applied ethanol potentiated LTCC activity in migrating GINs. Based on evidence reported in the present study, we conclude that calcium is an important intracellular intermediary downstream of GABAA receptor-mediated depolarization in the mechanistic scheme of an ethanol-induced aberrant tangential migration of embryonic GABAergic cortical interneurons.

Placental Production of Eicosanoids and Sphingolipids in Women Who Developed Preeclampsia on Low-Dose Aspirin.

Low-dose aspirin, which selectively inhibits thromboxane synthesis, is now standard of care for the prevention of preeclampsia in at risk women, but some women still develop preeclampsia despite an aspirin regimen. To explore the "aspirin failures," we undertook a comprehensive evaluation of placental lipids to determine if abnormalities in non-aspirin sensitive lipids might help explain why some women on low-dose aspirin develop preeclampsia. We studied placentas from women with normal pregnancies and women with preeclampsia. Placental villous explants were cultured and media analyzed by mass spectrometry for aspirin-sensitive and non-aspirin-sensitive lipids. In women who developed severe preeclampsia and delivered preterm, there were significant elevations in non-aspirin-sensitive lipids with biologic actions that could cause preeclampsia. There were significant increases in 15- and 20-hydroxyeicosatetraenoic acids and sphingolipids: D-e-C18:0 ceramide, D-e-C18:0 sphingomyelin, D-e-sphingosine-1-phosphate, and D-e-sphinganine-1-phosphate. With regard to lipids sensitive to aspirin, there was no difference in placental production of thromboxane or prostacyclin, but prostaglandins were lower. There was no difference for isoprostanes, but surprisingly, anti-inflammatory omega 3 and 6 PUFAs were increased. In total, 10 of 30 eicosanoids and 5 of 42 sphingolipids were abnormal in women with severe early onset preeclampsia. Lipid changes in women with mild preeclampsia who delivered at term were of lesser magnitude with few significant differences. The placenta produces many aspirin-sensitive and non-aspirin-sensitive lipids. Abnormalities in eicosanoids and sphingolipids not sensitive to aspirin might explain why some aspirin-treated women develop preeclampsia.

The NKCC1 antagonist bumetanide mitigates interneuronopathy associated with ethanol exposure in utero.

Prenatal exposure to ethanol induces aberrant tangential migration of corticopetal GABAergic interneurons, and long-term alterations in the form and function of the prefrontal cortex. We have hypothesized that interneuronopathy contributes significantly to the pathoetiology of fetal alcohol spectrum disorders (FASD). Activity-dependent tangential migration of GABAergic cortical neurons is driven by depolarizing responses to ambient GABA present in the cortical enclave. We found that ethanol exposure potentiates the depolarizing action of GABA in GABAergic cortical interneurons of the embryonic mouse brain. Pharmacological antagonism of the cotransporter NKCC1 mitigated ethanol-induced potentiation of GABA depolarization and prevented aberrant patterns of tangential migration induced by ethanol in vitro. In a model of FASD, maternal bumetanide treatment prevented interneuronopathy in the prefrontal cortex of ethanol exposed offspring, including deficits in behavioral flexibility. These findings position interneuronopathy as a mechanism of FASD symptomatology, and posit NKCC1 as a pharmacological target for the management of FASD.

Dynamic leadership emergence: Differential impact of members' and peers' contributions in the idea generation and idea enactment phases of innovation project teams.

Integrating functional leadership theory with models of the team creativity and innovation, we present a dynamic model of leadership emergence where leadership emergence is shaped by (a) the type of contributions members express (constructive contributions proposing new ideas, or supportive contributions affirming ideas with merit), (b) when those contributions are expressed (i.e., in the idea generation or idea enactment phase), and (c) the extent fellow teammates themselves are contributing in constructive or supportive ways in those phases. We tested our theoretical model in two studies involving simulated teams engaged in an innovation design challenge. In both studies, we found that constructive contributions were more strongly related to leadership emergence in the idea generation phase than in the idea enactment phase. Moreover, the impact of constructive contributions on leadership emergence in the idea generation phase was stronger when there was a "void"-that is, fellow teammates' constructive contributions were low. Surprisingly, in both studies, we found consistent evidence that supportive contributions also enhanced leadership emergence in the idea generation phase, whereas the findings on supportive contributions and leadership emergence in the idea enactment phase were mixed. Overall, our model highlights the importance of integrating dynamic and contextualized aspects of teams into theories of leadership emergence and also sheds new light on the processes underlying emergent forms of leadership in the early phases of the innovation cycle. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Single-Dose Levonorgestrel Emergency Contraception and Silent Barriers to Its Access: Is It Really Just One Step?

BACKGROUND: Single-dose levonorgestrel has been legally available over the counter in the United States without age restriction since 2013. The objective of this study was to discover if there are barriers to access and to determine if such barriers vary based on the gender of the person making the purchase. MATERIALS AND METHODS: A male and female caller contacted 146 Richmond, Virginia pharmacies listed on the Plan B One Step® website. Ultimately, these callers interviewed 90 pharmacies via phone and used a rehearsed standardized script to ask eight questions regarding emergency contraception (EC) in relation to availability, age restrictions, parental consent, counseling requirements, and a male's ability to purchase the product. The statistical data were analyzed using Fisher's exact test. RESULTS: Pharmacy employees provided incorrect information to both men and women regarding age restrictions for purchasing Plan B One Step 51% of the time. However, only seven of the pharmacy employees counseled that males were unable to purchase the medication. Both callers received correct information regarding parental consent and in-store counseling at the time of purchase. Pharmacy technicians provided the majority of information, and the male caller was more likely to be transferred to another person when requesting the medication (9 vs. 0 transfers for the male and female callers, respectively). CONCLUSION: Given the inconsistent data provided to the public regarding the purchase of EC, clinicians are obligated to convey accurate up-to-date information to patients about emergency contraceptive products as part of their counseling and should not assume that consumers receive accurate information when inquiring about over-the-counter EC.

Benefits of transformational behaviors for leaders: A daily investigation of leader behaviors and need fulfillment.

Although a large body of work has examined the benefits of transformational leadership, this work has predominantly focused on recipients of such behaviors. Recent research and theory, however, suggest that there are also benefits for those performing behaviors reflective of transformational leadership. Across 2 experience-sampling studies, we investigate the effects of such behaviors on actors' daily affective states. Drawing from affective events theory and self-determination theory we hypothesize and find that engaging in behaviors reflective of transformational leadership is associated with improvement in actors' daily affect, more so than engaging in behaviors reflective of transactional, consideration, initiating structure, and participative leadership. Behaviors reflective of transformational leadership improved actors' affect in part by fulfilling their daily needs. Furthermore, extraversion and neuroticism moderated these effects such that extraverts benefitted less whereas neurotics benefitted more from these behaviors in terms of affective changes. We consider the theoretical and practical implications of these findings and offer directions for future research.

Parabrachial Nucleus Contributions to Glucagon-Like Peptide-1 Receptor Agonist-Induced Hypophagia.

Exendin-4 (Ex4), a glucagon-like peptide-1 receptor (GLP-1R) agonist approved to treat type 2 diabetes mellitus, is well known to induce hypophagia in human and animal models. We evaluated the contributions of the hindbrain parabrachial nucleus (PBN) to systemic Ex4-induced hypophagia, as the PBN receives gustatory and visceral afferent relays and descending input from several brain nuclei associated with feeding. Rats with ibotenic-acid lesions targeted to the lateral PBN (PBNx) and sham controls received Ex4 (1 µg/kg) before 24 h home cage chow or 90 min 0.3 M sucrose access tests, and licking microstructure was analyzed to identify components of feeding behavior affected by Ex4. PBN lesion efficacy was confirmed using conditioned taste aversion (CTA) tests. As expected, sham control but not PBNx rats developed a CTA. In sham-lesioned rats, Ex4 reduced chow intake within 4 h of injection and sucrose intake within 90 min. PBNx rats did not show reduced chow or sucrose intake after Ex4 treatment, indicating that the PBN is necessary for Ex4 effects under the conditions tested. In sham-treated rats, Ex4 affected licking microstructure measures associated with hedonic taste evaluation, appetitive behavior, oromotor coordination, and inhibitory postingestive feedback. Licking microstructure responses in PBNx rats after Ex4 treatment were similar to sham-treated rats with the exception of inhibitory postingestive feedback measures. Together, the results suggest that the PBN critically contributes to the hypophagic effects of systemically delivered GLP-1R agonists by enhancing visceral feedback.