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Rationale: The majority of the morbidity and mortality related to chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries (LMICs). Despite the increasing burden of COPD, disease-specific knowledge among healthcare workers and patients in LMICs remains limited. COPD knowledge questionnaires (COPD-KQ) are valid and reliable tools to assess COPD knowledge and can be employed in settings with limited health literacy. Objectives: To develop and assess the validity and reliability of a COPD-KQ among individuals with COPD in three LMIC settings. Methods: Twelve questions were generated by an expert team of 16 researchers, physicians, and public health professionals to create an LMIC-specific COPD-KQ. The content was based on previous instruments, clinical guidelines, focus-group discussions, and questionnaire piloting. Participants with COPD completed the questionnaire across three diverse LMIC settings before and 3 months after delivery of a standardized COPD-specific education package by a local community health worker trained to deliver the education to an appropriate standard. We used paired t tests to assess improvement in knowledge after intervention. Results: Questionnaire development initially yielded 52 items. On the basis of community feedback and expertise, items were eliminated and added, yielding a final 12-item questionnaire, with a maximum total score of 12. A total of 196 participants with COPD were included in this study in Nepal (n = 86), Peru (n = 35), and Uganda (n = 75). The mean ± standard deviation baseline score was 8.0 ± 2.5, and 3 months after education, the mean score was 10.2 ± 1.7. The community health worker–led COPD educational intervention improved COPD knowledge among community members by 2.2 points (95% confidence interval, 1.8–2.6 points; t = 10.9; P

Purpose Appalachian residents have higher cancer prevalence and invasive cancer incidence in almost all cancer types relative to non-Appalachian residents. Public health interventions have been carried out to increase preventive cancer screening participation. However, no studies have evaluated the effectiveness of existing interventions targeting cancer screening uptake in this high-risk population. The main objective of this study is to assess the effectiveness of interventions aimed at increasing uptake and/or continuing participation in screened cancers (breast, cervical, colorectal, lung, and prostate) in Appalachia. Methods We conducted a systematic review of electronic databases and gray literature using a combination of MeSH and free-text search terms related to breast, cervical, colorectal, lung, and prostate cancer; mass screening; health promotion; and Appalachia. We identified 3,014 articles of which 15 articles were included. We assessed methodological quality using validated tools and analyzed findings using narrative synthesis. Findings Fifteen studies reported uptake and/or continued participation in screening interventions; these focused on cervical (n = 7), colorectal (n = 5), breast (n = 2), and lung (n = 1) cancers in Appalachia. Interventions included diverse components: mass media campaigns, community outreach events, community health workers, interpersonal counseling, and educational materials. We found that multi-strategy interventions had higher screening uptake relative to interventions employing 1 intervention strategy. Studies that targeted noncompliant populations and leveraged existing community-based organization partnerships had a substantial increase in screening participation versus others. Conclusions There is an urgent need for further research and implementation of effective cancer prevention and screening interventions to reduce disparities in cancer morbidity and mortality in Appalachian populations.

COVID-19 has heavily impacted the refugee population in the United States due to exposure risks, living and working conditions, and healthcare access, but little is known about outcomes. We reviewed emergency department visits to a Kentucky hospital among 2163 patients from March-December 2020, studying incidence of COVID-19 diagnosis for patients with a primary refugee-associated language compared to English speakers, and outcomes after diagnosis including hospitalization, length of stay, and in-hospital mortality. Patients in the population of interest had higher odds of COVID-19 diagnosis in the hospital (OR = 12.31, 95% CI 7.80-19.40), but, among those with COVID-19, lower odds of hospital admission (OR = 0.58, 95% CI 0.37-0.90) and shorter median length of stay (4.1 vs. 10.5 days) compared to English speakers. The study corroborates reports of comparatively higher COVID-19 incidence in patients speaking a primary refugee-associated language, but implies milder illness severity, possibly reflecting this population's baseline health.

Background Chronic vagus nerve stimulation (VNS) attenuates anxiety in rats and humans. However, it is unclear whether VNS can promote acute anxiolytic effects. Here we examined short-term anxiolytic effects of VNS using single or multiple trains in rats submitted to a battery of tests. Methods Three groups of rats were implanted with VNS cuffs and tested for anxiety using the elevated plus maze (EPM), novelty suppressed feeding (NSF), and acoustic startle response (ASR), after receiving either one or five VNS trains (0.4 mA/30 Hz/30-sec), or sham stimulation. Results Both single and multiple VNS trains reduced state anxiety as measured using the EPM, but only multiple trains reduced anxiety in the EPM and NSF. VNS trains did not decrease arousal as measured using the ASR. Limitations The anxiolytic effects of VNS may be differently influenced by test order or prior-exposure to stress. VNS did not affect startle responses in naive rats but the present findings do not determine whether VNS would affect startle responses that are potentiated by fear or anxiety. Conclusion A single VNS train can produce an anxiolytic effect minutes later, an effect that is not observed in a novelty-suppressed feeding. Delivering 5 VNS trains restores the immediate effects across tests of anxiety, indicating that more trains produce a more robust anxiolytic effect. The lack of effects on ASR suggests that VNS affects state anxiety but not baseline arousal in naive rats. We suggest that the anxiolytic effect of VNS can increase tolerability and reduce dropout in exposure-based therapies.

Introduction: Almost 90% of chronic obstructive pulmonary disease (COPD) deaths occur in low- and middle-income countries (LMICs), where there are large rural populations and access to health care for COPD is poor. The purpose of this study was to compare urban-rural provider experiences regarding systemic facilitators and barriers to COPD management and treatment access. Methods: We conducted a qualitative study using direct observations and in-depth semi-structured interviews with 16 and 10 health care providers in urban Kampala and rural Nakaseke, Uganda, respectively. We analyzed interviews by performing inductive coding using generated topical codes. Results: In both urban and rural districts, exposure to evidence-based practices for COPD diagnosis and treatment was limited. The biomedical definition of COPD is not well distinguished in rural communities and was commonly confused with asthma and other respiratory diseases. Urban and rural participants alike described low availability of medications, limited access to diagnostic tools, poor awareness of the disease, and lack of financial means for medical care as common barriers to seeking and receiving care for COPD. While there was greater access to COPD treatment in urban areas, rural populations faced more pronounced barriers in access to diagnostic equipment, following standard treatment guidelines, and training medical personnel in non-communicable disease (NCD) management and treatment. Conclusion: Our results suggest that health system challenges for the treatment of COPD may disproportionately affect rural areas in Uganda. Implementation of diagnostic and treatment guidelines and training health professionals in COPD, with a special emphasis on rural communities, will assist in addressing these barriers.

Studies in rodents indicate that pairing vagus nerve stimulation (VNS) with extinction training enhances fear extinction. However, the role of stimulation parameters on the effects of VNS remains largely unknown. Identifying the optimal stimulation intensity is a critical step in clinical translation of neuromodulation-based therapies. Here, we sought to investigate the role of stimulation intensity in rats receiving VNS paired with extinction training in a rat model for Posttraumatic Stress Disorder (PTSD). Male Sprague-Dawley rats underwent single prolonged stress followed by a severe fear conditioning training and were implanted with a VNS device. After recovery, independent groups of rats were exposed to extinction training paired with sham (0 mA) or VNS at different intensities (0.4, 0.8, or 1.6 mA). VNS intensities of 0.4 mA or 0.8 mA decreased conditioned fear during extinction training compared to sham stimulation. Pairing extinction training with moderate VNS intensity of 0.8 mA produced significant reduction in conditioned fear during extinction retention when rats were tested a week after VNS-paired extinction. High intensity VNS at 1.6 mA failed to enhance extinction. These findings indicate that a narrow range of VNS intensities enhances extinction learning, and suggest that the 0.8 mA VNS intensity used in earlier rodent and human stroke studies may also be the optimal in using VNS as an adjuvant in exposure therapies for PTSD.

Background Poor cervical cancer screening coverage and utilization by women in low- and middle-income countries (LMICs) are linked to health system factors such as lack of access and availability of quality health care, inadequate workforce capacity, and socio-cultural and behavioral barriers. To improve women’s participation in cervical screening, strategies such as involvement of community resources have been recommended. The aim of this review is to understand the current roles of community-based resources (CBRs) such as community health workers (CHWs) and community-based civil society organizations (CBOs) including key stakeholders – for example health champions, traditional leaders, chief’s wives, etc. in the community in cervical screening in LMICs settings. Methods and analysis We will conduct a scoping review of MEDLINE, CINAHL and Global Health databases from January 2016 to June 2020 for published peer-reviewed literature from LMICs including reference list tracking and handsearching of studies with community focus published in English describing interventions provided by CBRs in cervical screening uptake. Ethics and dissemination Ethical approval is not required. Findings from this review will be summarised for conferences and published in peer-reviewed journals for widespread dissemination. Study will identify possible gaps in the evidence and differences in the role of CBRs between sub-Saharan Africa (SSA) and other LMIC regions and inform recommendations and implementation of future cervical screening research, policy, and practice.

More than 90% of chronic obstructive pulmonary disease (COPD)-related deaths occur in low- and middle-income countries; however, few studies have examined the illness experiences of individuals living with and providing treatment for COPD in these settings. This study characterizes illness representations for COPD in Nakaseke, Uganda from the perspectives of health care providers, village health teams and community members (CMs) with COPD. We conducted 40 in-depth, semi-structured interviews (16 health care providers, 12 village health teams and 12 CMs, aged 25–80 years). Interviews were analyzed using inductive coding, and the Illness Representations Model guided our analysis. Stakeholder groups showed concordance in identifying causal mechanisms of COPD, but showed disagreement in reasons for care seeking behaviors and treatment preferences. CMs did not use a distinct label to differentiate COPD from other respiratory illnesses, and described both the physical and social consequences of COPD. Local representations can inform development of adapted educational and self-management tools for COPD.

Background Fear conditioning (FC) in rodents is the most used animal model to investigate the neurobiology of posttraumatic stress disorder (PTSD). Although research using FC has generated a better understanding of fear memories, studies often rely on mild or moderate FC training and behavioral analysis generally focuses on measuring freezing responses within few test sessions. New method We introduce the M-Maze task, a system that measures extinction of conditioned fear using suppression of operant behavior. The apparatus consists of an M-shaped maze where rats are trained to alternate nose poking at two pellet dispensers. Proximity sensors measure the animal’s locomotion, as well as the latencies and number of operant behaviors. Here we also describe the protracted aversive conditioning (PAC), a rat model of severe fear that induces resistant extinction following a 4-day conditioning protocol that combines delay, unpredictable, and short- and long-trace conditioning. Results An intense one-day auditory FC protocol induced a sharp elevation in transit time and suppression of nose pokes by conditioned cues, but in contrast to what is found in PTSD patients, fear extinction was rapidly observed. On the other hand, PAC alone or in combination with exposure to single prolonged stress induced persistent extinction impairments in M-Maze tests, as well as enhanced anxiety, and social withdrawal. Comparison with other existing methods The M-Maze task is fully automated and allows multiple animals to be tested simultaneously in long-term experiments. Moreover, PAC training can be an alternative approach to study extinction-resistant fear. Conclusions The M-Maze task allows rapid and unbiased measurements of fear-induced suppression. We suggest that long-term assessment of extinction impairments would lead to a better understanding of the neurobiology of persistent fear and the screening for new therapies.

Background Pulmonary tuberculosis (TB) is the leading infectious cause of death globally with an estimated 1.7 billion people currently infected with Mycobacterium tuberculosis and at risk of developing TB. While the treatment of drug-susceptible pulmonary TB is highly effective, up to 50% of TB survivors have varying degrees of residual pathological and functional conditions potentially leading to chronic sequelae. Post-TB patients have reported respiratory symptoms, reduced quality of life, and increased risk of mortality. The objectives of this study are to describe the prevalence and lung function in individuals with post-TB exposure status in Uganda. Methods We performed a secondary data analysis of the Lung Function in Nakaseke and Kampala (LiNK) study, which is a population-based cohort in urban and rural settings in Uganda. Trained fieldworkers randomly selected homes and administered standard questionnaires to adults 35 years or older that were full-time residents of each setting. Prior TB diagnosis and treatment was self-reported by participants. Results Among the study population (N = 1559), 50 participants (3.2%) self-reported successfully treated TB. Among this subset of participants 21 (42.0%) were HIV positive, 9 (18.0%) were ever smokers, 6 (12.0%) were current smokers, and no participants had a prior COPD diagnosis. Mean (SD) age and body-mass index (BMI) at enrollment was 48.5 (SD 10.7) years and 22.2 (SD 3.9) kg/m2 respectively. The mean ± SD pre-bronchodilator FEV1/FVC was 72.9% (12.1%) for patients with successfully treated TB and 79.6% (0.08%) (p< 0.0001) for those without prior TB. Within these groups, 30% of patients with successfully treated TB and 9% of patients without prior TB had an FEV1/FVC suggestive of possible COPD. Comparison of FEV1/FVC Conclusion We found a high burden of residual effects of pulmonary TB on lung function and development of COPD, potentially increasing the global burden of COPD. Screening for chronic respiratory diseases following successful TB treatment is needed to improve lung function. Further research is needed to study lung function and quality of life in TB survivors in LMICs, where the burden of pulmonary TB is highest. Disclosures All Authors: No reported disclosures

OBJECTIVES: We aimed to quantify the burden of cardiometabolic risk factors (CMRF) in South American children. METHODS: We included primary quantitative white and gray literature in any language reporting after 1999 on the prevalence of glucose intolerance, obesity, hypertension and/or dyslipidemia in South Americans aged 2–21 years old. Studies were excluded for lack of available data, population with additional comorbidity, and/or CMRF criteria not defined. We searched PubMed, the Latin American and Caribbean Health Sciences Literature, and Google Scholar and performed reference handsearching. We assigned data quality via Effective Public Healthcare Panacea Project Quality Assessment Tool for Quantitative Studies modified for selection bias and data collection. We analyzed CMRF by available sociodemographic variables. RESULTS: Included studies (68 of 1,179; n = 115,674 children aged 2–19 years) came from 8 countries (Argentina, Brazil, Chile, Colombia, Ecuador, Paraguay, Peru and Venezuela). CMRF definitions ranged widely. By any definition, 33.41% (n = 4,480/13,408) had low HDL cholesterol, 25.33% (n = 3,396/13,408) had elevated triglycerides, 13.92% (n = 2,900/20,830) had elevated waist circumference, 10.38% (n = 3,909/37,646) were obese by any definition, 10.49% (n = 858/9,672) had elevated blood pressure (BP), and 5.62% (n = 1,015/15,270) had glucose intolerance. By International Diabetes Federation definitions, 33.39% (n = 3,495/10,466) had HDL ≤ 40 mg/dL (16/22 studies); 23.45% (n = 909/3,876) had triglycerides ≥ 150 mg/dL (6/22 studies); 8.84% (n = 1,373/15,533) had waist circumference ≥ 90% for age, gender and height (20/30 studies); 6.10% (n = 733/12,010) had fasting glucose ≥ 100 mg/dL (17/21 studies) and 14.04% (n = 404/2,877) had systolic BP ≥ 130 mmHg (4/4 studies). CMRF varied by country, study setting (rural, urban or mixed), and indigenous population. Overall, Brazil had the highest prevalence of glucose intolerance and elevated BP; Chile had the highest prevalence of obesity and low HDL. Obesity was more prevalent in rural settings (7/65 studies); urban settings (19/28) had increased dyslipidemia. CONCLUSIONS: South American children experience a high prevalence of CMRF and need further characterization of the sociomedical determinants of their risk. FUNDING SOURCES: None.

We have shown that vagus nerve stimulation (VNS) enhances extinction of conditioned fear and reduces anxiety in rat models of PTSD using moderate stress. However, it is still unclear if VNS can be effective in enhancing extinction of severe fear after prolonged and repeated trauma. Severe fear was induced in adult male rats by combining single prolonged stress (SPS) and protracted aversive conditioning (PAC). After SPS and PAC procedures, rats were implanted with stimulating cuff electrodes, exposed to five days of extinction training with or without VNS, and then tested for extinction retention, return of fear in a new context and reinstatement. The elevated plus maze, open field and startle were used to test anxiety. Sham rats showed no reduction of fear during extensive extinction training. VNS-paired with extinction training reduced freezing at the last extinction session by 70% compared to sham rats. VNS rats exhibited half as much fear as shams, as well as less fear renewal. Sham rats exhibited significantly more anxiety than naive controls, whereas VNS rats did not. These results demonstrate that VNS enhances extinction and reduces anxiety in a severe model of PTSD that combined SPS and a conditioning procedure that is 30 times more intense than the conditioning procedures in previous VNS studies. The broad utility of VNS in enhancing extinction learning in rats and the strong clinical safety record of VNS suggest that VNS holds promise as an adjuvant to exposure-based therapy in people with PTSD and other complex forms of this condition.

As urbanization increases in low- and middle-income countries (LMICs), urban populations will be increasingly exposed to a range of environmental risk factors for non-communicable diseases. Inadequate living conditions in urban settings may influence mechanisms that regulate gene expression, leading to the development of non-communicable respiratory diseases. We conducted a systematic review of the literature to assess the relationship between respiratory health and epigenetic factors to urban environmental exposures observed in LMICs using MEDLINE, PubMed, EMBASE, and Google Scholar searching a combination of the terms: epigenetics, chronic respiratory diseases (CRDs), lung development, chronic obstructive airway disease, and asthma. A total of 2835 articles were obtained, and 48 articles were included in this review. We found that environmental factors during early development are related to epigenetic effects that may be associated with a higher risk of CRDs. Epigenetic dysregulation of gene expression of the histone deacetylase (HDAC) and histone acetyltransferase gene families was likely involved in lung health of slum dwellers. Respiratory-related environmental exposures influence HDAC function and deoxyribonucleic acid methylation and are important risk factors in the development of CRD. Additional epigenetic research is needed to improve our understanding of associations between environmental exposures and non-communicable respiratory diseases.

Vagus nerve stimulation (VNS) has shown promise as an adjuvant treatment for posttraumatic stress disorder (PTSD), as it enhances fear extinction and reduces anxiety symptoms in multiple rat models of this condition. Yet, identification of the optimal stimulation paradigm is needed to facilitate clinical translation of this potential therapy. Using an extinction-resistant rat model of PTSD, we tested whether varying VNS intensity and duration could maximize extinction learning while minimizing the total amount of stimulation. We confirmed that sham rats failed to extinguish after a week of extinction training. Delivery of the standard LONG VNS trains (30 s) at 0.4 mA enhanced extinction and reduced anxiety but did not prevent fear return. Increasing the intensity of LONG VNS trains to 0.8 mA prevented fear return and attenuated anxiety symptoms. Interestingly, delivering 1, 4 or 16 SHORT VNS bursts (0.5 s) at 0.8 mA during each cue presentation in extinction training also enhanced extinction. LONG VNS trains or multiple SHORT VNS bursts at 0.8 mA attenuated fear renewal and reinstatement, promoted extinction generalization and reduced generalized anxiety. Delivering 16 SHORT VNS bursts also facilitated extinction in fewer trials. This study provides the first evidence that brief bursts of VNS can enhance extinction training, reduce relapse and support symptom remission using much less VNS than previous protocols. These findings suggest that VNS parameters can be adjusted in order to minimize total charge delivery and maximize therapeutic effectiveness.

Recovery from serious neurological injury requires substantial rewiring of neural circuits. Precisely-timed electrical stimulation could be used to restore corrective feedback mechanisms and promote adaptive plasticity after neurological insult, such as spinal cord injury (SCI) or stroke. This study provides the first evidence that closed-loop vagus nerve stimulation (CLV) based on the synaptic eligibility trace leads to dramatic recovery from the most common forms of SCI. The addition of CLV to rehabilitation promoted substantially more recovery of forelimb function compared to rehabilitation alone following chronic unilateral or bilateral cervical SCI in a rat model. Triggering stimulation on the most successful movements is critical to maximize recovery. CLV enhances recovery by strengthening synaptic connectivity from remaining motor networks to the grasping muscles in the forelimb. The benefits of CLV persist long after the end of stimulation because connectivity in critical neural circuits has been restored., eLife digest The spine houses a network of neurons that relays electric signals from the brain cells to the muscles. When the spine is injured, some of these neurons may be damaged and their connections to the muscles broken. As a result, the muscles they command become weak, and movement is impaired. It is possible to strengthen the remaining neural connections with physical rehabilitation, but the results are limited. Vagus nerve stimulation, VNS for short, is a new technique that could help people recuperate better after their spine is injured. The vagus nerve controls the heart, lungs and guts, and it reports the state of the body to the brain. When this nerve is electrically stimulated, it releases chemicals that can strengthen the neural connections between brain, spine and muscles, and even create new ones. This rewiring process is essential to repair or bypass the broken neural connections caused by a spine injury. However, it is still not clear how best to use VNS to optimize recovery. Here, Ganzer et al. study how VNS helps rats whose forelimbs are weakened after a spine injury. Three groups of rats go through physical rehabilitation, using their affected front paws to pull a handle and feed themselves. Two of these groups also receive VNS: their vagus nerve is stimulated either after the best trials (strongest pulls) or worst trials (weakest pulls). Compared to the rehab-only and the worst trials-VNS animals, the rats that receive VNS on the best trials while using their affected paw have many more neuronal connections between their brain and the muscles in this limb. These muscles also become much stronger. VNS during the movement improves recovery whether the rodents have one or two front limbs injured, and the benefits are long lasting. As the rats pull the handle, the neurons involved in the movement get activated: they then carry a molecular ‘signature’ that lasts for a short time. When VNS is applied during that window, it appears to help these neurons form new connections with each other, as well as strengthen existing ones. These improved connections mean the brain can communicate better with the muscles: movement is enhanced, which results in greater functional recovery compared to rehabilitation alone. VNS is already trialed in stroke patients, who have weakened muscles because their brain neurons are damaged. The work by Ganzer et al. provides crucial information on how VNS could ultimately improve the recovery and quality of life of people with spine injuries.