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Article ; Online: Efference copies: Side-eyeing across species.

Leary, Paige / Schoppik, David

2022 Volume 32, Issue 2, Page(s) R91–R93

Abstract: Efference copies of movement-inducing neural signals have been proposed to serve a role in gaze stabilization. Prior work has demonstrated a spino-extraocular motor circuit in the tadpole that relays copies of spinal commands to extraocular motor neurons. ...

Abstract	Efference copies of movement-inducing neural signals have been proposed to serve a role in gaze stabilization. Prior work has demonstrated a spino-extraocular motor circuit in the tadpole that relays copies of spinal commands to extraocular motor neurons. A recent study demonstrates the presence of this circuitry in mice, suggesting a unique method of gaze stabilization in the locomoting mouse.
MeSH term(s)	Animals ; Eye Movements ; Larva ; Mice
Language	English
Publishing date	2022-01-24
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2021.12.002
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Article: Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer's disease.

Chartampila, Elissavet / Elayouby, Karim S / Leary, Paige / LaFrancois, John J / Alcantara-Gonzalez, David / Jain, Swati / Gerencer, Kasey / Botterill, Justin J / Ginsberg, Stephen D / Scharfman, Helen E

bioRxiv : the preprint server for biology

2024

Abstract: Maternal choline supplementation (MCS) improves cognition in Alzheimer's disease (AD) models. However, effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated effects of MCS in a well-established mouse model of AD with ... ...

Abstract	Maternal choline supplementation (MCS) improves cognition in Alzheimer's disease (AD) models. However, effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse. The most common type of hyperexcitability in Tg2576 mice, and many other mouse models and AD patients, are generalized EEG spikes (interictal spikes; IIS). Hyperexcitability is also reflected by elevated expression of the transcription factor ΔFosB in the granule cells (GCs) of the dentate gyrus (DG), which are the principal cell type. We also studied the hilus of the DG because hilar neurons regulate GC excitability. We found reduced expression of the neuronal marker NeuN within hilar neurons in Tg2576 mice, which other studies have shown is a sign of oxidative stress or other pathology. Tg2576 breeding pairs received a diet with a relatively low, intermediate or high concentration of choline. After weaning, all mice received the intermediate diet. In offspring of mice fed the high choline diet, IIS frequency declined, GC ΔFosB expression was reduced, and NeuN expression was restored. Spatial memory improved using the novel object location task. In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB. However, their IIS frequency was low, which was surprising. The results provide new evidence that a diet high in choline in early life can improve outcomes in a mouse model of AD, and relatively low choline can have mixed effects. This is the first study showing that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB and spatial memory in an animal model of AD.
Language	English
Publishing date	2024-02-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.12.540428
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Article: Motor neurons are dispensable for the assembly of a sensorimotor circuit for gaze stabilization.

Goldblatt, Dena / Rosti, Başak / Hamling, Kyla R / Leary, Paige / Panchal, Harsh / Li, Marlyn / Gelnaw, Hannah / Huang, Stephanie / Quainoo, Cheryl / Schoppik, David

bioRxiv : the preprint server for biology

2024

Abstract: Sensorimotor reflex circuits engage distinct neuronal subtypes, defined by precise connectivity, to transform sensation into compensatory behavior. Whether and how motor neuron populations specify the subtype fate and/or sensory connectivity of their pre- ...

Abstract	Sensorimotor reflex circuits engage distinct neuronal subtypes, defined by precise connectivity, to transform sensation into compensatory behavior. Whether and how motor neuron populations specify the subtype fate and/or sensory connectivity of their pre-motor partners remains controversial. Here, we discovered that motor neurons are dispensable for proper connectivity in the vestibular reflex circuit that stabilizes gaze. We first measured activity following vestibular sensation in pre-motor projection neurons after constitutive loss of their extraocular motor neuron partners. We observed normal responses and topography indicative of unchanged functional connectivity between sensory neurons and projection neurons. Next, we show that projection neurons remain anatomically and molecularly poised to connect appropriately with their downstream partners. Lastly, we show that the transcriptional signatures that typify projection neurons develop independently of motor partners. Our findings comprehensively overturn a long-standing model: that connectivity in the circuit for gaze stabilization is retrogradely determined by motor partner-derived signals. By defining the contribution of motor neurons to specification of an archetypal sensorimotor circuit, our work speaks to comparable processes in the spinal cord and advances our understanding of general principles of neural development.
Language	English
Publishing date	2024-01-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.25.577261
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Article ; Online: The epidemiology of pediatric traumatic brain injury presenting at a referral center in Moshi, Tanzania.

Barcenas, Loren K / Appenteng, Roselyn / Sakita, Francis / O'Leary, Paige / Rice, Henry / Mmbaga, Blandina T / Vissoci, Joao Ricardo Nickenig / Staton, Catherine A

PloS one

2022 Volume 17, Issue 10, Page(s) e0273991

Abstract: Background: Over 95% of childhood injury deaths occur in low- and middle-income countries (LMICs). Patients with severe traumatic brain injury (TBI) have twice the likelihood of dying in LMICs than in high-income countries (HICs). In Africa, TBI ... ...

Abstract	Background: Over 95% of childhood injury deaths occur in low- and middle-income countries (LMICs). Patients with severe traumatic brain injury (TBI) have twice the likelihood of dying in LMICs than in high-income countries (HICs). In Africa, TBI estimates are projected to increase to upwards of 14 million new cases in 2050; however, these estimates are based on sparse data, which underscores the need for robust injury surveillance systems. We aim to describe the clinical factors associated with morbidity and mortality in pediatric TBI at the Kilimanjaro Christian Medical Centre (KCMC) in Moshi, Tanzania to guide future prevention efforts. Methods: We conducted a secondary analysis of a TBI registry of all pediatric (0-18 years of age) TBI patients presenting to the KCMC emergency department (ED) between May 2013 and April 2014. The variables included demographics, acute treatment and diagnostics, Glasgow Coma Scores (GCSs, severe 3-8, moderate 9-13, and mild 14-15), morbidity at discharge as measured by the Glasgow Outcome Scale (GOS, worse functional status 1-3, better functional status 4-6), and mortality status at discharge. The analysis included descriptive statistics, bivariable analysis and multivariable logistic regression to report the predictors of mortality and morbidity. The variables used in the multivariable logistic regression were selected according to their clinical validity in predicting outcomes. Results: Of the total 419 pediatric TBI patients, 286 (69.3%) were male with an average age of 10.12 years (SD = 5.7). Road traffic injury (RTI) accounted for most TBIs (269, 64.4%), followed by falls (82, 19.62%). Of the 23 patients (5.58%) who had alcohol-involved injuries, most were male (3.6:1). Severe TBI occurred in 54 (13.0%) patients. In total, 90 (24.9%) patients underwent TBI surgery. Of the 21 (5.8%) patients who died, 11 (55.0%) had severe TBI, 6 (30.0%) had moderate TBI (GCS 9-13) and 3 (15.0%) presented with mild TBI (GCS>13). The variables most strongly associated with worse functional status included having severe TBI (OR = 9.45) and waiting on the surgery floor before being moved to the intensive care unit (ICU) (OR = 14.37). Conclusions: Most pediatric TBI patients were males who suffered RTIs or falls. Even among children under 18 years of age, alcohol was consumed by at least 5% of patients who suffered injuries, and more commonly among boys. Patients becoming unstable and having to be transferred from the surgery floor to the ICU could reflect poor risk identification in the ED or progression of injury severity. The next steps include designing interventions to reduce RTI, mitigate irresponsible alcohol use, and improve risk identification and stratification in the ED.
MeSH term(s)	Adolescent ; Brain Concussion/complications ; Brain Injuries, Traumatic/complications ; Child ; Female ; Glasgow Coma Scale ; Glasgow Outcome Scale ; Humans ; Male ; Referral and Consultation ; Tanzania/epidemiology
Language	English
Publishing date	2022-10-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0273991
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Article ; Online: Utility of Family Reports in Predicting Emergency Department Patient Alcohol Use in Tanzania.

Kozhumam, Arthi S / Lovvorn, Carter / O'Leary, Paige / Minja, Linda / Boshe, Judith / Vissoci, João Ricardo Nickenig / Mmbaga, Blandina T / Staton, Catherine A

Journal of studies on alcohol and drugs

2022 Volume 83, Issue 5, Page(s) 760–767

Abstract: Objective: Myriad reasons, including stigma, may prevent patients from self-reporting harmful use of alcohol in Tanzania. Family members may be more forthright but might not know the extent of the patient's alcohol use or suffer alcohol-related stigma ... ...

Abstract	Objective: Myriad reasons, including stigma, may prevent patients from self-reporting harmful use of alcohol in Tanzania. Family members may be more forthright but might not know the extent of the patient's alcohol use or suffer alcohol-related stigma as well. Our study aims to compare the reporting of patient alcohol use by emergency department patients themselves and their family members in Tanzania in order to describe the potential use of family reports as a proxy for patient self-reports. Method: We conducted a secondary descriptive analysis of a prospective cohort of adult patients seeking treatment for injury and their family members. We evaluated alcohol use behavior, alcohol-related consequences, and alcohol-related stigma reported by 231 patients and 231 family members (both majority male, ages 25-45 years), measured by the Alcohol Use Disorders Identification Test (AUDIT), Perceived Alcohol Stigma (PAS) scale, and the Drinker Inventory of Consequences (DrInC). Alcohol use behavior concordance/discordance between patients and families was established, and alcohol use and perceived stigma were analyzed. Results: More than 72% of patient-family pairs showed alcohol use (AUDIT) concordance. Receiver operating characteristic curve and regression analysis suggests family reports to be clinically relevant, significant, and potentially accurate markers of patient alcohol use (sensitivity: 95.10%, specificity: 69.77%). Findings support the existence of stigma toward alcohol in this context, with similar stigma levels of patients and family members. Conclusions: Family-reported patient alcohol use may be an accurate proxy for patient self-reporting. Further research is needed into stigma toward alcohol that is culturally appropriate and adopted.
MeSH term(s)	Adult ; Alcoholism/complications ; Alcoholism/diagnosis ; Alcoholism/epidemiology ; Emergency Service, Hospital ; Family ; Humans ; Male ; Middle Aged ; Prospective Studies ; Social Stigma ; Tanzania/epidemiology
Language	English
Publishing date	2022-12-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2266450-6
ISSN	1938-4114 ; 1934-2683 ; 1937-1888 ; 0096-882X
ISSN (online)	1938-4114 ; 1934-2683
ISSN	1937-1888 ; 0096-882X
DOI	10.15288/jsad.21-00141
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Article ; Online: Enhanced excitability of the hippocampal CA2 region and its contribution to seizure activity in a mouse model of temporal lobe epilepsy.

Whitebirch, Alexander C / LaFrancois, John J / Jain, Swati / Leary, Paige / Santoro, Bina / Siegelbaum, Steven A / Scharfman, Helen E

Neuron

2022 Volume 110, Issue 19, Page(s) 3121–3138.e8

Abstract: The hippocampal CA2 region, an area important for social memory, has been suspected to play a role in temporal lobe epilepsy (TLE) because of its resistance to degeneration observed in neighboring CA1 and CA3 regions in both humans and rodent models of ... ...

Abstract	The hippocampal CA2 region, an area important for social memory, has been suspected to play a role in temporal lobe epilepsy (TLE) because of its resistance to degeneration observed in neighboring CA1 and CA3 regions in both humans and rodent models of TLE. However, little is known about whether alterations in CA2 properties promote seizure generation or propagation. Here, we addressed the role of CA2 using the pilocarpine-induced status epilepticus model of TLE. Ex vivo electrophysiological recordings from acute hippocampal slices revealed a set of coordinated changes that enhance CA2 PC intrinsic excitability, reduce CA2 inhibitory input, and increase CA2 excitatory output to its major CA1 synaptic target. Moreover, selective chemogenetic silencing of CA2 pyramidal cells caused a significant decrease in the frequency of spontaneous seizures measured in vivo. These findings provide the first evidence that CA2 actively contributes to TLE seizure activity and may thus be a promising therapeutic target.
MeSH term(s)	Animals ; CA2 Region, Hippocampal ; Disease Models, Animal ; Epilepsy, Temporal Lobe/chemically induced ; Hippocampus/physiology ; Humans ; Mice ; Pilocarpine/toxicity ; Pyramidal Cells/physiology ; Seizures/chemically induced
Chemical Substances	Pilocarpine (01MI4Q9DI3)
Language	English
Publishing date	2022-08-19
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2022.07.020
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Article ; Online: Six-month incidence of hypertension and diabetes among adults with HIV in Tanzania: A prospective cohort study.

Sakita, Francis M / O'Leary, Paige / Prattipati, Sainikitha / Kessy, Monica S / Kilonzo, Kajiru G / Mmbaga, Blandina T / Rugakingira, Anzibert A / Manavalan, Preeti / Thielman, Nathan M / Samuel, Dorothy / Hertz, Julian T

PLOS global public health

2023 Volume 3, Issue 8, Page(s) e0001929

Abstract: Data describing the incidence of hypertension and diabetes among people with HIV in sub-Saharan Africa remain sparse. In this study, adults with HIV were enrolled from a public clinic in Moshi, Tanzania (September 2020-March 2021). At enrollment, a ... ...

Abstract	Data describing the incidence of hypertension and diabetes among people with HIV in sub-Saharan Africa remain sparse. In this study, adults with HIV were enrolled from a public clinic in Moshi, Tanzania (September 2020-March 2021). At enrollment, a survey was administered to collect information on comorbidities and medication use. Each participant's blood pressure and point-of-care glucose were measured. Baseline hypertension was defined by blood pressure ≥140/90 mmHg or self-reported hypertension at enrollment. Baseline diabetes was defined by self-reported diabetes or hyperglycemia (fasting glucose ≥126 mg/dl or random glucose ≥200 mg/dl) at enrollment. At 6-month follow-up, participants' blood pressure and point-of-care glucose were again measured. Incident hypertension was defined by self-report of new hypertension diagnosis or blood pressure ≥140/90 mmHg at follow-up in a participant without baseline hypertension. Incident diabetes was defined as self-report of new diabetes diagnosis or measured hyperglycemia at follow-up in a participant without baseline diabetes. During the study period, 477 participants were enrolled, of whom 310 did not have baseline hypertension and 457 did not have baseline diabetes. At six-month follow-up, 51 participants (95% CI: 38, 67) had new-onset hypertension, corresponding to an incidence of 33 new cases of hypertension per 100 person-years. Participants with incident hypertension at 6-month follow-up were more likely to have a history of alcohol use (90.2% vs. 73.7%, OR = 3.18, 95% CI:1.32-9.62, p = 0.008) and were older (mean age = 46.5 vs. 42.3, p = 0.027). At six-month follow-up, 8 participants (95% CI: 3, 16) had new-onset diabetes, corresponding to an incidence of 3 new cases of diabetes per 100 person-years. In conclusion, the incidence of elevated blood pressure and diabetes among Tanzanians with HIV is higher than what has been reported in high-income settings.
Language	English
Publishing date	2023-08-21
Publishing country	United States
Document type	Journal Article
ISSN	2767-3375
ISSN (online)	2767-3375
DOI	10.1371/journal.pgph.0001929
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Article ; Online: A feasibility assessment of a traumatic brain injury predictive modelling tool at Kilimanjaro Christian Medical Center and Duke University Hospital.

O'Leary, Paige / Domeracki, Alexis / Raymond, Julius / Kozhumam, Arthi / Macha, Victoria / Sakita, Francis / Krym, Valerie / Riccardo Nickenig Vissoci, Joao / Staton, Catherine

PLOS global public health

2023 Volume 3, Issue 11, Page(s) e0002154

Abstract: Traumatic brain injury (TBI) is the most common cause of death and disability globally. TBI, which disproportionately affects low middle-income countries (LMIC), uses significant amounts of health system resources in costly care and management. ... ...

Abstract	Traumatic brain injury (TBI) is the most common cause of death and disability globally. TBI, which disproportionately affects low middle-income countries (LMIC), uses significant amounts of health system resources in costly care and management. Innovative solutions are required to address this high burden of TBI. One possible solution is prognostic models which enhance diagnostic ability of physicians, thereby helping to tailor treatments more effectively. This study aims to evaluate the feasibility of a TBI prognostic model developed in Tanzania for use by Kilimanjaro Christian Medical Center (KCMC) healthcare providers and Duke-affiliated healthcare providers using human centered design methodology. Duke participants were included to gain insight from a different context with more established practices to inform the TBI tool implementation strategy at KCMC. To evaluate the feasibility of integrating the TBI tool into potential workflows, co-design interviews were conducted with emergency physicians and nursing staff at KCMC and Duke. Qualitatively, the TBI tool was assessed using human centered design (HCD) techniques. Our research design methods were created using the Consolidated Framework for Implementation Research which considers overarching characteristics of successful implementation to contribute to theory development and verification of implementation strategies across multiple contexts. Our knowledge translation method was guided using the knowledge-to-action framework. Of the 21 participants interviewed, 12 were associated with Duke Hospital, and 9 from Kilimanjaro Christian Medical Centre. Emerging from the data were 6 themes that impacted the implementation of the TBI tool: access, barriers, facilitators, use of the TBI tool, outer setting, and inner setting. To our knowledge, this is the first study to investigate the pre-implementation of a sub-Saharan Africa (SSA) data- based TBI prediction tool using human centered design methodology. Findings of this study will aid in determining under what conditions a TBI prognostic model intervention will work at KCMC.
Language	English
Publishing date	2023-11-28
Publishing country	United States
Document type	Journal Article
ISSN	2767-3375
ISSN (online)	2767-3375
DOI	10.1371/journal.pgph.0002154
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Conference proceedings ; Online: Confidentiality and Consent in Health Research With Youth Living in Zimbabwe

Stewart, Kearsley / Aimone, Elizabeth / O'Leary, Paige / Koris, Andrea

Ethical Challenges for the Responsible Conduct of Health Research Using Social Media in Africa

2020

Abstract: BACKGROUND: The explosive growth of mobile telephone ownership and social media use in Africa introduces new modes of communication, education, information sharing, and opportunities for research and data generation. COVID-19 physical distancing, ... ...

Abstract	BACKGROUND: The explosive growth of mobile telephone ownership and social media use in Africa introduces new modes of communication, education, information sharing, and opportunities for research and data generation. COVID-19 physical distancing, quarantine and lockdowns have impacted the way that people socialize, leading many to use social media platforms to stay connected. The beneficial impact of social media services on access to health information and improving health behaviors and outcomes is well-known. Less well understood are the challenges of using social media platforms to generate data for health research in Africa, and appropriate ethical guidelines for the responsible conduct of social media health research in Africa. The visuality of social media renders all-but-impossible many of the central principles of traditional research ethics (confidentiality and anonymity). The networked nature of social media calls for a new definition of informed consent. OBJECTIVES: We seek to define the distinct ethics of the responsible conduct of health-related social media research in Africa. METHODS: In-depth qualitative interviews, surveys, and focus group discussions, with Zimbabwean Research Ethics Professionals and youth Zimbabwe. FINDINGS: We describe adolescent-users’ perceptions of risk and expectations of privacy when sharing personal health data on social media and during research. We assess the robustness of current IRB ethics guidelines for health-related social media research in Zimbabwe. NEXT STEPS: A scoping review will identify and classify the current range of social media-based health interventions and make recommendations for appropriate frameworks to increase the ethical conduct of health-related social media research in Africa.
Keywords	covid19
Publishing date	2020-08-10T18:03:06Z
Publishing country	us
Document type	Conference proceedings ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Six month incidence of major adverse cardiovascular events among adults with HIV in northern Tanzania: a prospective observational study.

Stark, Kristen / O'Leary, Paige R E / Sakita, Francis M / Ford, James S / Mmbaga, Blandina T / Blass, Beau / Gedion, Kalipa / Coaxum, Lauren A / Rutta, Alice / Galson, Sophie Wolfe / Rugakingira, Anzibert / Manavalan, Preeti / Bloomfield, Gerald S / Hertz, Julian T

BMJ open

2023 Volume 13, Issue 11, Page(s) e075275

Abstract: Objectives: We aimed to prospectively describe incident cardiovascular events among people living with HIV (PLWH) in northern Tanzania. Secondary aims of this study were to understand non-communicable disease care-seeking behaviour and patient ... ...

Abstract	Objectives: We aimed to prospectively describe incident cardiovascular events among people living with HIV (PLWH) in northern Tanzania. Secondary aims of this study were to understand non-communicable disease care-seeking behaviour and patient preferences for cardiovascular care and education. Design: A prospective observational study. Setting: This study was conducted at the Majengo HIV Care and Treatment Clinic, an outpatient government-funded clinic in Moshi, Tanzania PARTICIPANTS: Adult patients presenting to an HIV clinic for routine care in northern Tanzania were enrolled from 1 September 2020 to 1 March 2021. Interventions: At enrolment, participants completed a survey and a resting 12-lead ECG was obtained. At 6 month follow-up, a repeat survey regarding interim health events and repeat ECG was obtained. Primary and secondary outcome measures: Interim major adverse cardiovascular events (MACE) were defined by: self-reported interim stroke, self-reported hospitalisation for heart failure, self-reported interim myocardial infarction, interim myocardial infarction by ECG criteria (new pathologic Q waves in two contiguous leads) or death due to cardiovascular disease (CVD). Results: Of 500 enrolled participants, 477 (95.4%) completed 6 month follow-up and 3 (0.6%) died. Over the 6 month follow-up period, 11 MACE occurred (3 strokes, 6 myocardial infarctions, 1 heart failure hospitalisation and 1 cardiovascular death), resulting in an incidence rate of 4.58 MACE per 100 person-years. Of participants completing 6 month follow-up, 31 (6.5%) reported a new non-communicable disease diagnosis, including 23 (4.8%) with a new hypertension diagnosis. Conclusions: The incidence of MACE among PLWH in Tanzania is high. These findings are an important preliminary step in understanding the landscape of CVD among PLWH in Tanzania and highlight the need for interventions to reduce cardiovascular risk in this population.
MeSH term(s)	Humans ; Adult ; Incidence ; Tanzania/epidemiology ; Noncommunicable Diseases ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/etiology ; Myocardial Infarction/epidemiology ; HIV Infections/complications ; HIV Infections/epidemiology ; Heart Failure ; Risk Factors
Language	English
Publishing date	2023-11-19
Publishing country	England
Document type	Observational Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-075275
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