We Aren't Just 'Slack'ing Off: Utilizing a Digital Tool to Connect Emerging Women Leaders in Global Health.

Background: Investing in women leaders in global health catalyzes growth and positive outcomes for individuals and their communities, yet large gender disparities persist in leadership within the field due to several barriers. The use of digital tools facilitates cross-institutional and international collaborations to allow individuals or groups to create or share information, ideas, career interests, and other forms of expression via virtual communities. Digital tools can dramatically expand access to and the quantity and quality of opportunities for networking, mentoring, and collaboration to support women in their professional development. Objectives: The objective of this paper is to document tangible examples of positive experiences, connections, or collaborations resulting from connecting with other participants in a Slack network. We aimed to evaluate this network to understand how to better build, model, and scale advantageous digital networks of women leaders in global health moving forward. Methods: Semi-structured interviews were conducted virtually with seven members of the Slack network from Africa and North America who volunteered to share their experiences. Transcripts of six of these interviews were analyzed for key points using thematic analysis to derive short vignettes from each interview. Findings: The findings of this study indicate that Slack is a highly beneficial tool for women in global health to use for facilitating job searches, mentoring opportunities, promoting project collaborations, and proposing programming and outreach ideas in a remote environment. We found distinct recommendations for utilizing this digital networking tool in a way that best supports and engages women in global health. It is important to spread awareness and ensure visibility of the network to recruit and maintain members, design the network in a way that inspires internal motivation, encourage consistent and meaningful engagement, send weekly emails, and maintain accessibility for a global membership base. Conclusions: The Slack network provides an engaging digital tool that facilitates communication, opportunities, and growth among women in global health. Digital tools such as Slack can help to increase opportunities for participants from low- and-middle-income countries to engage in the same networking and leadership opportunities as individuals from high-income countries. It remains critical to continue to build, advance, and scale advantageous networks like Slack to promote equity and accessibility among women leaders in the global north and south into the post-pandemic world.

Strategies to Improve Women's Leadership Preparation for Early Career Global Health Professionals: Suggestions from Two Working Groups.

Background: Despite advances in gender equality, women still experience inequitable gaps in global health leadership, and barriers to women's advancement as leaders in global health have been well described in the literature. In 2021, the Johns Hopkins Center for Global Health conducted two virtual working groups for emerging women leaders to share challenges and suggest solutions to advance women's leadership in global health. In this paper, we present emerging themes from the working groups, provide a framework for the results, and discuss strategies for advancing women's leadership in global health. Objectives: The objective of this paper is to synthesize and share the themes of the two working group sessions to provide strategies for improving women's leadership training and opportunities in the field of global health. Methods: Approximately 182 women in the global health field participated in two virtual working group sessions hosted by the Johns Hopkins Center for Global Health using the Zoom platform. Participants were divided into virtual breakout rooms and discussed pre-assigned topics related to women's leadership in global health. The participants then returned to share their ideas in a plenary session. Notes from the breakout rooms and transcripts from the plenary session were analyzed through a participatory and iterative thematic analysis approach. Findings: We found that the working group participants identified two overarching themes that were critical for emerging women leaders to find success in global health leadership. First, the acquisition of individual essential skills is necessary to advance in their careers. Second, the institutional environments should be setup to encourage and enable women to enter and succeed in leadership roles. The participants also shared suggestions for improving women's leadership opportunities such as including the use of virtual technologies to increase training and networking opportunities, intersectionality in mentorship and sponsorship, combatting impostor syndrome, and the importance of work-life balance. Conclusions: Investing in women and their leadership potential has the promise to improve health and wealth at the individual, institutional, and community levels. This manuscript offers lessons and proposes solutions for increasing women's leadership through improving individual level essential skills and fostering environments in which women leaders can emerge and thrive.

Evaluation of a Virtual Networking Event for Emerging Women Leaders in Global Health.

Background: Networks are critical for leadership development, but not all networks and networking activities are created equally. Women and people of color face unique challenges accessing networks, many of which were exacerbated during the COVID-19 pandemic. Virtual platforms offer opportunities for global professionals to connect and can be better tailored to meet the needs of different groups. As part of the Consortium of Universities for Global Health annual meeting in 2021, we organized a networking session to provide a networking space for emerging women leaders in global health (i.e. trainees, early career professionals, and/or those transitioning to the field). Objectives: We evaluated the virtual networking session to better understand participants' perception of the event and its utility for professional growth and development. Methods: We distributed online surveys to participants immediately after the event and conducted a 3-month follow-up. Out of 225 participant, 24 responded to both surveys and their data was included in the analysis. We conducted descriptive quantitative analysis for multiple choice and Likert scale items; qualitative data was analyzed for themes. Findings: Participants represented 8 countries and a range of organizations. Participants appreciated the structure of the networking session; all participants agreed that they met someone from a different country and most indicated they had plans to collaborate with a new connection. When asked if the event strengthened their network and if they will keep in touch with new people, most participants strongly agreed or agreed in both surveys. However, after the follow-up, participants noted challenges in sustaining connections including lack of follow-up and misaligned expectations of networks. Conclusions: The virtual networking event brought together women in global health from diverse backgrounds. This study found that while networking events can be impactful in enhancing professional networks, ensuring sustained connections remains a challenge. This study also suggests that measures to increase the depth and meaningfulness of these connections in a virtual setting and enabling post-event collaboration can help networks become more inclusive and sustainable.

Possible Role of Parvalbumin Interneurons in Meditation and Psychiatric Illness.

Parvalbumin (PV) interneurons are present in multiple brain regions and produce complex influences on brain functioning. An increasing number of research findings indicate that the function of these interneurons is more complex than solely to inhibit pyramidal neurons in the cortex. They generate feedback and feedforward inhibition of cortical neurons, and they are critically involved in the generation of neuronal network oscillation. These oscillations, generated by various brain regions, are linked to perceptions, thought processes, and cognitive functions, all of which, in turn, influence human emotions and behavior. Both animal and human studies consistently have found that meditation practice results in enhancement in the effects of alpha-, theta-, and gamma-frequency oscillations, which may correspond to positive changes in cognition, emotion, conscious awareness, and, subsequently, behavior. Although the study of meditation has moved into mainstream neuroscience research, the link between PV interneurons and any role they might play in meditative states remains elusive. This article is focused primarily on gamma-frequency oscillation, which is generated by PV interneurons, to develop insight and perspective into the role of PV interneurons in meditation. This article also points to new and emerging directions that address whether this role of PV interneurons in meditation extends to a beneficial, and potentially therapeutic, role in the treatment of common psychiatric disorders, including schizophrenia.

No Family Should Suffer From Cervical Cancer Twice-The Palliative Care Role in HPV Prevention.

BACKGROUND: Cervical cancer, caused by human papillomavirus infection, is the source of significant personal and societal burden, and robs more than one hundred thousand Indian women and their families of the chances of a healthy and productive life each year. As outlined by the World Health Organization, the three-pronged approach of screening, vaccination, and reduction in mortality by early treatment presents the possibility of the elimination of cervical cancer as a public health problem in the next decade.1 Unfortunately, these approaches are all associated with significant barriers in India. OBJECTIVES: Given that the main mandate of palliative care practitioners to prevent and relieve suffering, here we make the case for these practitioners to offer education around vaccination and screening to female relatives of women encountered with cervical cancer. CONCLUSION: Offering prevention strategies for human papillomavirus aligns with the idea of preventing suffering and is within the scope of palliative care clinicians.

Exo- and Endo-cannabinoids in Depressive and Suicidal Behaviors.

Cannabis (marijuana) has been known to humans for thousands of years but its neurophysiological effects were sparsely understood until recently. Preclinical and clinical studies in the past two decades have indisputably supported the clinical proposition that the endocannabinoid system plays an important role in the etiopathogeneses of many neuropsychiatric disorders, including mood and addictive disorders. In this review, we discuss the existing knowledge of exo- and endo-cannabinoids, and role of the endocannabinoid system in depressive and suicidal behavior. A dysfunction in this system, located in brain regions such as prefrontal cortex and limbic structures is implicated in mood regulation, impulsivity and decision-making, may increase the risk of negative mood and cognition as well as suicidality. The literature discussed here also suggests that the endocannabinoid system may be a viable target for treatments of these neuropsychiatric conditions.

A team science approach to discover novel targets for infantile spasms (IS).

Infantile spasms (IS) is a devastating epilepsy syndrome that typically begins in the first year of life. Symptoms consist of stereotypical spasms, developmental delay, and electroencephalogram (EEG) that may demonstrate Hypsarhythmia. Current therapeutic approaches are not always effective, and there is no reliable way to predict which patient will respond to therapy. Given this disorder's complexity and the potential impact of a disease-modifying approach, Citizens United for Research in Epilepsy (CURE) employed a "team science" approach to advance the understanding of IS pathology and explore therapeutic modalities that might lead to the development of new ways to potentially prevent spasms and Hypsarhythmia. This approach was a first-of-its-kind collaborative initiative in epilepsy. The IS initiative funded 8 investigative teams over the course of 1-3 years. Projects included the following: discovery on the basic biology of IS, discovery of novel therapeutic targets, cross-validation of targets, discovery of biomarkers, and prognosis and treatment of IS. The combined efforts of a strong investigative team led to numerous advances in understanding the neural pathways underlying IS, testing of small molecules in preclinical models of IS and generated preliminary data on potential biomarkers. Thus far, the initiative has resulted in over 19 publications and subsequent funding for several investigators. Investigators reported that the IS initiative generally affected their research positively due to its collaborative and iterative nature. It also provided a unique opportunity to mentor junior investigators with an interest in translational research. Learnings included the need for a dedicated project manager and more transparent and real-time communication with investigators. The CURE IS initiative represents a unique approach to fund scientific discoveries on epilepsy. It brought together an interdisciplinary group of investigators-who otherwise would not have collaborated-to find transformative therapies for IS. Learnings from this initiative are being utilized for subsequent initiatives at CURE.

Pulmonary artery catheter use in adult patients undergoing cardiac surgery: a retrospective, cohort study.

BACKGROUND: The utility of pulmonary artery catheters (PACs) and their measurements depend on a variety of factors including data interpretation and personnel training. This US multi-center, retrospective electronic health record (EHR) database analysis was performed to identify associations between PAC use in adult cardiac surgeries and effects on subsequent clinical outcomes. METHODS: This cohort analysis utilized the Cerner Health Facts database to examine patients undergoing isolated coronary artery bypass graft (CABG), isolated valve surgery, aortic surgery, other complex non-valvular and multi-cardiac procedures, and/or heart transplant from January 1, 2011, to June 30, 2015. A total of 6844 adults in two cohorts, each with 3422 patients who underwent a qualifying cardiac procedure with or without the use of a PAC for monitoring purposes, were included. Patients were matched 1:1 using a propensity score based upon the date and type of surgery, hospital demographics, modified European System for Cardiac Operative Risk Evaluation (EuroSCORE II), and patient characteristics. Primary outcomes of 30-day in-hospital mortality, length of stay, cardiopulmonary morbidity, and infectious morbidity were analyzed after risk adjustment for acute physiology score. RESULTS: There was no difference in the 30-day in-hospital mortality rate between treatment groups (OR, 1.17; 95% CI, 0.65-2.10; p = 0.516). PAC use was associated with a decreased length of stay (9.39 days without a PAC vs. 8.56 days with PAC; p < 0.001), a decreased cardiopulmonary morbidity (OR, 0.87; 95% CI, 0.79-0.96; p < 0.001), and an increased infectious morbidity (OR, 1.28; 95% CI, 1.10-1.49; p < 0.001). CONCLUSIONS: Use of a PAC during adult cardiac surgery is associated with decreased length of stay, reduced cardiopulmonary morbidity, and increased infectious morbidity but no increase in the 30-day in-hospital mortality. This suggests an overall potential benefit associated with PAC-based monitoring in this population. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov (NCT02964026) on November 15, 2016.

Association between albumin administration and survival in cardiac surgery: a retrospective cohort study.

PURPOSE: Albumin is widely used during and after on-pump cardiac surgery, although it is unclear whether this therapy improves clinical outcomes. METHODS: This observational study utilized the Cerner Health Facts® database (a large HIPAA-compliant clinical-administrative database maintained by Cerner Inc., USA) to identify a cohort of 6,188 adults that underwent on-pump cardiac surgery for valve and/or coronary artery procedures between January 2001 and March 2013. Of these, 1,095 patients who received 5% albumin with crystalloid solutions and 1,095 patients who received crystalloids alone on the day of or the day following cardiac surgery were selected by propensity-score matching. The primary outcome was all-cause in-hospital mortality. Three secondary outcomes analyzed include acute kidney injury severity, major morbidity composite, and all-cause 30-day readmissions. RESULTS: In the propensity-score matched cohort, receipt of perioperative 5% albumin was associated with decreased risk of in-hospital mortality (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.3 to 0.9; P = 0.02) and lower all-cause 30-day readmission rates (OR, 0.7; 98.3% CI, 0.5 to 0.9; P < 0.01). Albumin therapy was not associated with differences in overall major morbidity (OR, 0.9; 98.3% CI, 0.7 to 1.2; P = 0.39; composite) or acute kidney injury severity (OR, 0.9; 98.3% CI, 0.6 to 1.4; P = 0.53) compared with therapy with crystalloid solutions. CONCLUSIONS: In this large retrospective study, use of 5% albumin solution was associated with significantly decreased odds of in-hospital mortality and all-cause 30-day readmission rate compared with administration of crystalloids alone in adult patients undergoing on-pump cardiac surgery. These results warrant further studies to examine fluid receipt, including 5% albumin, in surgical populations via randomized-controlled trials.

Identification and characterization of outcome measures reported in animal models of epilepsy: Protocol for a systematic review of the literature-A TASK2 report of the AES/ILAE Translational Task Force of the ILAE.

Current antiseizure therapy is ineffective in approximately one third of people with epilepsy and is often associated with substantial side effects. In addition, most current therapeutic paradigms offer treatment, but not cure, and no therapies are able to modify the underlying disease, that is, can prevent or halt the process of epileptogenesis or alleviate the cognitive and psychiatric comorbidities. Preclinical research in the field of epilepsy has been extensive, but unfortunately, not all the animal models being used have been validated for their predictive value. The overall goal of TASK2 of the AES/ILAE Translational Task Force is to organize and coordinate systematic reviews on selected topics regarding animal research in epilepsy. Herein we describe our strategy. In the first part of the paper we provide an overview of the usefulness of systematic reviews and meta-analysis for preclinical research and explain the essentials for their conduct. Then we describe in detail the protocol for a first systematic review, which will focus on the identification and characterization of outcome measures reported in animal models of epilepsy. The specific goals of this study are to define systematically the phenotypic characteristics of the most commonly used animal models, and to effectively compare these with the manifestations of human epilepsy. This will provide epilepsy researchers with detailed information on the strengths and weaknesses of epilepsy models, facilitating their refinement and future research. Ultimately, this could lead to a refined use of relevant models for understanding the mechanism(s) of the epilepsies and developing novel therapies.

The effects of lacosamide on cognition, quality-of-life measures, and quality of life in patients with refractory partial epilepsy.

OBJECTIVE: The objective of this study was to examine cognitive and quality-of-life measures/quality of life outcomes with adjunctive lacosamide therapy in patients with treatment-resistant partial epilepsy. METHODS: This was a prospective, open-label, nonblinded, adjunctive therapy test-retest (within subjects) study of patients with treatment-resistant partial epilepsy in which outcome (cognitive functioning and mood/quality of life) was measured in the same subject before and after adjunctive lacosamide administration for 24weeks. The cognitive assessment included the following: Controlled Oral Word Association Test, Buschke Selective Reminding Test, Brief Visuospatial Memory Test-Revised, Stroop Color Word Test, Symbol Digit Modalities Test, Digit Span, Digit Cancellation, and Trails A and B. The quality-of-life measures/quality-of-life assessment included the following: Beck Depression Inventory-II, Profile of Mood States, and Quality of Life Inventory-89. Lacosamide was started at 100mg (50mg twice daily) and could be titrated as needed up to 400mg/day (200mg twice daily). Baseline concomitant AEDs were kept constant. Composite scores were calculated for a pre-post difference score for the cognitive and mood/quality-of-life measures separately and used in regression analyses to correct for the effects of age, education, seizure frequency, seizure severity, dose of lacosamide, and number of AEDs at baseline. RESULTS: Thirty-four patients were enrolled (13 males, 21 females). Mean age was 38.8±2.43years. Mean seizure frequency decreased significantly from 2.0±2.55 seizures per week at baseline to 1.02±1.72 seizures per week at posttreatment (t=4.59, p<.0001) with a 50% responder rate seen in 18 patients (52.9%). No significant differences were found on the composite scores of the cognitive or the mood/quality-of-life measures after 6months of lacosamide. SIGNIFICANCE: Lacosamide appeared to have low risks of significant changes in cognition or mood/quality of life. In addition, the present study supports prior studies that have proven lacosamide as an effective adjunctive therapy for the treatment of resistant partial epilepsy.

Suppression of adult neurogenesis increases the acute effects of kainic acid.

Adult neurogenesis, the generation of new neurons in the adult brain, occurs in the hippocampal dentate gyrus (DG) and the olfactory bulb (OB) of all mammals, but the functions of these new neurons are not entirely clear. Originally, adult-born neurons were considered to have excitatory effects on the DG network, but recent studies suggest a net inhibitory effect. Therefore, we hypothesized that selective removal of newborn neurons would lead to increased susceptibility to the effects of a convulsant. This hypothesis was tested by evaluating the response to the chemoconvulsant kainic acid (KA) in mice with reduced adult neurogenesis, produced either by focal X-irradiation of the DG, or by pharmacogenetic deletion of dividing radial glial precursors. In the first 4 hrs after KA administration, when mice have the most robust seizures, mice with reduced adult neurogenesis had more severe convulsive seizures, exhibited either as a decreased latency to the first convulsive seizure, greater number of convulsive seizures, or longer convulsive seizures. Nonconvulsive seizures did not appear to change or they decreased. Four-21 hrs after KA injection, mice with reduced adult neurogenesis showed more interictal spikes (IIS) and delayed seizures than controls. Effects were greater when the anticonvulsant ethosuximide was injected 30 min prior to KA administration; ethosuximide allows forebrain seizure activity to be more easily examined in mice by suppressing seizures dominated by the brainstem. These data support the hypothesis that reduction of adult-born neurons increases the susceptibility of the brain to effects of KA.

Spike-wave discharges in adult Sprague-Dawley rats and their implications for animal models of temporal lobe epilepsy.

Spike-wave discharges (SWDs) are thalamocortical oscillations that are often considered to be the EEG correlate of absence seizures. Genetic absence epilepsy rats of Strasbourg (GAERS) and Wistar Albino Glaxo rats from Rijswijk (WAG/Rij) exhibit SWDs and are considered to be genetic animal models of absence epilepsy. However, it has been reported that other rat strains have SWDs, suggesting that SWDs may vary in their prevalence, but all rats have a predisposition for them. This is important because many of these rat strains are used to study temporal lobe epilepsy (TLE), where it is assumed that there is no seizure-like activity in controls. In the course of other studies using the Sprague-Dawley rat, a common rat strain for animal models of TLE, we found that approximately 19% of 2- to 3-month-old naive female Sprague-Dawley rats exhibited SWDs spontaneously during periods of behavioral arrest, which continued for months. Males exhibited SWDs only after 3 months of age, consistent with previous reports (Buzsáki et al., 1990). Housing in atypical lighting during early life appeared to facilitate the incidence of SWDs. Spike-wave discharges were often accompanied by behaviors similar to stage 1-2 limbic seizures. Therefore, additional analyses were made to address the similarity. We observed that the frequency of SWDs was similar to that of hippocampal theta rhythm during exploration for a given animal, typically 7-8 Hz. Therefore, activity in the frequency of theta rhythm that occurs during frozen behavior may not reflect seizures necessarily. Hippocampal recordings exhibited high frequency oscillations (>250 Hz) during SWDs, suggesting that neuronal activity in the hippocampus occurs during SWDs, i.e., it is not a passive structure. The data also suggest that high frequency oscillations, if rhythmic, may reflect SWDs. We also confirmed that SWDs were present in a common animal model of TLE, the pilocarpine model, using female Sprague-Dawley rats. Therefore, damage and associated changes to thalamic, hippocampal, and cortical neurons do not prevent SWDs, at least in this animal model. The results suggest that it is possible that SWDs occur in rodent models of TLE and that investigators mistakenly assume that they are stage 1-2 limbic seizures. We discuss the implications of the results and ways to avoid the potential problems associated with SWDs in animal models of TLE.

Neuregulin blocks synaptic strengthening after epileptiform activity in the rat hippocampus.

Synaptic strengthening produced by epileptiform activity may contribute to seizure progression and cognitive impairment in epilepsy. Agents that limit this form of plasticity may have therapeutic benefit. Neuregulin is an endogenous growth factor that is released at synapses in an activity dependent manner and can suppress long term potentiation (LTP). Alterations in neuregulin signaling have been associated with schizophrenia. A role for neuregulin in epilepsy has not been explored. We used field potential recordings to examine the role of neuregulin in regulating synaptic strengthening following epileptiform activity in hippocampal slices. Neuregulin had no effect on basal synaptic transmission, isolated NMDA field potentials or GABAergic inhibition on CA1 pyramidal neurons. However, it reversed LTP at CA1 synapses. Brief exposure to 10 mM potassium chloride produced epileptiform bursting and potentiation of CA1 synapses and suppressed the subsequent induction of LTP. Neuregulin reversed high K(+)-induced synaptic strengthening, enabling LTP induction after neuregulin washout. In this manner neuregulin preserved the dynamic range of synaptic responses and plasticity after epileptiform activity. These results indicate that LTP and high K(+)-induced synaptic strengthening share a common neuregulin-sensitive mechanism. By opposing synaptic strengthening caused by epileptiform activity, we suggest that neuregulin may reduce the generation and spread of seizures as well as memory deficits associated with epilepsy.